case report form

CASE REPORT FORM Title:

A Randomized, Double blind, Single dose, Phase I Study to Investigate the Pharmacokinetics, Safety, and Tolerability of Intravenous dosage form of ABC123 in Healthy Male Volunteers

Sponsor:

MAMA Pharm.

Site:

Department of Clinical Pharmacology and Therapeutics Asan Medical Center, 88, Olympic-ro 43-gil, Songpa-gu, Seoul 05505, Korea

Principal Investigator:

Kyun-seop Bae M.D., Ph.D.

Protocol ID:

ABC-01

Product:

ABC123

Screening ID

A B C S

Subject ID

A B C

Subject Initials CRF Version:

1.0

CRF Date:

2016.10.01

CONFIDENTIAL

page 1 of 101

Screening (-28D~-2D)

CONFIDENTIAL

page 2 of 101

Product: ABC123 CRF Version: 1.0 Protocol ID: ABC-01

Screening ID A B C S

Screening (-28D~-2D)

Sponsor: MAMA Pharm. Subject ID Subject Initials A B C

Visit Date Date

y

y

y

y

m

m

d

d

d

d

Informed Consent Date Date

y

y

y

y

m

m

y

y

y

y

m

m

Demographics Date of birth Age Sex

years

Male Female

Race

Asian Black or African American White Native Hawaiian or Other Pacific Islander

Nationality

Korean Other

CONFIDENTIAL

page 3 of 101

Product: ABC123 CRF Version: 1.0 Protocol ID: ABC-01 Screening (-28D~-2D)

Sponsor: MAMA Pharm. Subject ID Subject Initials A B C

Screening ID A B C S

Substance Use Tobacco

ND

Current:

cigarettes/day

Former: Date of Quit y

y

y

y

m

m

d

d

Never Alcohol

units/week

Caffeine

cups/day

CONFIDENTIAL

page 4 of 101

Product: ABC123 CRF Version: 1.0 Protocol ID: ABC-01 Screening (-28D~-2D)

Screening ID A B C S

Sponsor: MAMA Pharm. Subject ID Subject Initials A B C

Medical History

ND

Any medical history?

Yes No

Details

Start date

Progress

Participation

1

y

y

y

y

m

Recovery

Yes

Ongoing

No

Recovery

Yes

Ongoing

No

Recovery

Yes

Ongoing

No

Recovery

Yes

Ongoing

No

Recovery

Yes

Ongoing

No

m

2

y

y

y

y

m

m

3

y

y

y

y

m

m

4

y

y

y

y

m

m

5

y

CONFIDENTIAL

y

y

y

m

m

page 5 of 101

Product: ABC123 CRF Version: 1.0 Protocol ID: ABC-01

Sponsor: MAMA Pharm. Subject ID Subject Initials A B C

Screening ID A B C S

Screening (-28D~-2D)

Physical Examination Check Remarkable findings?

ND

Yes No

Prior/Concomitant Medication Check Any prior/concomitant medications?

ND

Yes No

Physical Measurement Date

y

y

ND

y

y

m

Weight

m

d

d

kg

Height

cm

BMI

kg/m 2

Vital Sign

ND

Sitting position / Tympanic temperature Date and time

y

y

y

y

m

SBP

mmHg

DBP

mmHg

PR

bpm

TEMP

O

CONFIDENTIAL

m

d

d

H

H

M

M

C page 6 of 101

Product: ABC123 CRF Version: 1.0 Protocol ID: ABC-01

Sponsor: MAMA Pharm. Subject ID Subject Initials A B C

Screening ID A B C S

Screening (-28D~-2D)

Urine Cotinine Test

ND

Pass Fail

Urine Drug Screening

ND

Pass Fail

Laboratory Test - Blood Date and time

y

Type of test

y

* Value: EMR export

y

y

CONFIDENTIAL

m

d

d

Hematology

Laboratory Test - Urine Date and time

m

y

y

H

H

ND

M

M

Coagulation

Chemistry

* Value: EMR export

y

y

m

m

d

d

H

H

Serology

ND

M

M

page 7 of 101

Product: ABC123 CRF Version: 1.0 Protocol ID: ABC-01

Sponsor: MAMA Pharm. Subject ID Subject Initials A B C

Screening ID A B C S

Screening (-28D~-2D)

12-lead ECG Date and time

ND

y

y

y

y

m

Ventricular rate

bpm

PR interval

msec

QRS

msec

QT

msec

QTc

msec

Clinically significant

m

d

d

H

H

M

M

Yes No

CONFIDENTIAL

page 8 of 101

Product: ABC123 CRF Version: 1.0 Protocol ID: ABC-01 Screening (-28D~-2D)

Screening ID A B C S

Sponsor: MAMA Pharm. Subject ID Subject Initials A B C

Selection Criteria Inclusion criteria 1. Healthy male volunteers between the ages of 19 and 40 years (19 =< age < 40) on the day of screening

ND

Yes

No

NA

2. Body Mass Index (BMI) between 19 to 28kg/m2 (19kg/m2 =< BMI < 28kg/m2) and weight at least 50kg on the day of screening 3. Medically healthy with no clinically significant findings on vital signs on the day of screening 4. Medically healthy with no clinically significant findings on physical examinations on the day of screening 5. Medically healthy with no clinically significant findings on laboratory results except AST, ALT, ALP(Alkaline Phosphatase) or Bilirubin total described in Exclusion Criterion 10. on the day of screening 6. Agree to use effective or medically appropriate dual contraceptive methods and avoid sperm donation from the date of the first dose, during the course of the study and for a period of 28 days following the last dose 7. Subjects who are willing to comply with the requirements of the study and voluntarily consent to participate in the study

CONFIDENTIAL

page 9 of 101

Product: ABC123 CRF Version: 1.0 Protocol ID: ABC-01 Screening (-28D~-2D)

Screening ID A B C S

Sponsor: MAMA Pharm. Subject ID Subject Initials A B C

Selection Criteria(Cont.) Exclusion criteria 1. Subjects with clinically significant medical or surgical history described below - History of inflammatory bowel disease(Crohn's disease or ulcerative colitis) or surgery (excluding simple appendectomy or herniorrhaphy) which may affect absorption, distribution, metabolism or elimination of the investigational product

Yes

No

NA

- History of clinically significant allergy, cardiovascular, mucocutaneous, ocular, ear, nose and throat (ENT), respiratory, musculoskeletal, infectious, gastrointestinal, liver, biliary, endocrine, renal, genitourinary, nervous, psychiatric, blood disorders, tumors, fractures or any other conditions. 2. History of hypersensitivity, allergic or adverse reactions to ABC123, the same class drug (QWERTY, POIUY or any other drugs) or the other drugs (Aspirin, antibiotics or any other drugs) 3. Donated blood or blood components or had been transfused plasma within 60 days prior to the day of screening 4. Administered other drug(s) in other clinical study within 90 days prior to the day of screening 5. Use of any prescription medication within 14 days or over-the-counter (OTC) medication within 7 days prior to the day of screening 6. Tobacco use within 30 days prior to the day of screening 7. Use of any health supplement or herbal products within 30 days prior to the day of screening 8. Positive urine screen for drugs and/or cotinine on the day of screening 9. Positive blood screen for human immunodeficiency virus (HIV), hepatitis B or C, or syphilis on the day of screening 10. Positive laboratory results described below on the day of screening - AST, ALT, or Alkaline Phosphatase(ALP) > 2.0 folds of upper limit of reference range - Bilirubin total > 2.0 folds of upper limit of reference range 11. QTc interval greater than 450 ms (QTc > 450 ms) or clinically significant results of 12-lead ECG on the day of screening 12. Clinically significant observations considered as unsuitable based on medical judgment by investigators

CONFIDENTIAL

page 10 of 101

Product: ABC123 CRF Version: 1.0 Protocol ID: ABC-01 Screening (-28D~-2D)

Screening ID A B C S

Sponsor: MAMA Pharm. Subject ID Subject Initials A B C

Eligibility Is the subject eligible for this study?

Yes No

Reason for screeining failure

Unsuitable by selection criteria Consent Withdrawal Surplus

Completed by Signature with date

Reviewed by Signature with date

CONFIDENTIAL

page 11 of 101

Period 1 (-1D~2D)

CONFIDENTIAL

page 12 of 101

Product: ABC123 CRF Version: 1.0 Protocol ID: ABC-01

Sponsor: MAMA Pharm. Subject ID Subject Initials A B C

Screening ID A B C S

Period 1 (-1D~2D) / -1D

Visit Date Date

y

y

y

y

m

m

d

d

Vital Sign

ND

Sitting position / Tympanic temperature Date and time

y

y

y

y

m

SBP

mmHg

DBP

mmHg

PR

bpm

TEMP

O

m

d

d

H

H

M

M

C

Urine Cotinine Test

ND

Pass Fail

Laboratory Test - Blood Date and time

y

Type of test

y

* Value: EMR export

y

y

CONFIDENTIAL

m

d

d

Hematology

Laboratory Test - Urine Date and time

m

y

y

H

H

ND

M

M

Coagulation

Chemistry

* Value: EMR export

y

y

m

m

d

d

H

H

Serology

ND

M

M

page 13 of 101

Product: ABC123 CRF Version: 1.0 Protocol ID: ABC-01

Sponsor: MAMA Pharm. Subject ID Subject Initials A B C

Screening ID A B C S

Period 1 (-1D~2D) / -1D

12-lead ECG Date and time

ND

y

y

y

y

m

Ventricular rate

bpm

PR interval

msec

QRS

msec

QT

msec

QTc

msec

Clinically significant

m

d

d

H

H

M

M

Yes No

Physical Examination Check Remarkable findings?

ND

Yes No

Prior/Concomitant Medication Check Any prior/concomitant medications?

ND

Yes No

Check-in Assessment Is it okay to continue to participate?

Yes No

CONFIDENTIAL

page 14 of 101

Product: ABC123 CRF Version: 1.0 Protocol ID: ABC-01

Screening ID A B C S

Period 1 (-1D~2D) / -1D

Sponsor: MAMA Pharm. Subject ID Subject Initials A B C

Randomization Was the subject randomized into the study?

Yes No

Date - Randomization No.

y

y

y

y

m

m

d

d

A B C

- Sequence No.

1: ABC123 IV 300 mg -> ABC123 PO 600 mg 2: ABC123 PO 600 mg -> ABC123 IV 300 mg

Adverse Event Check Clinically significant findings?

ND

Yes No

CONFIDENTIAL

page 15 of 101

Product: ABC123 CRF Version: 1.0 Protocol ID: ABC-01

Sponsor: MAMA Pharm. Subject ID Subject Initials A B C

Screening ID A B C S

Period 1 (-1D~2D) / 1D

Visit Date Date

y

y

y

y

m

m

d

d

Drug Administration Was the study drug administrated to the subject?

Yes No

Start date and time

y

End time

y

y

y

m

m

d

d

(Acceptable:60+-5min)

H

H

M

M

H

H

M

M

NA

Study drug Dose

300

Unit

mg

600 Route

IV PO

CONFIDENTIAL

Fasting status

Yes No

page 16 of 101

Product: ABC123 CRF Version: 1.0 Protocol ID: ABC-01

Screening ID A B C S

Period 1 (-1D~2D) / 1D

Adverse Event Check

Sponsor: MAMA Pharm. Subject ID Subject Initials A B C ND

Clinically significant findings?

Yes No

Physical Examination Check Remarkable findings?

ND

Yes No

Prior/Concomitant Medication Check Any prior/concomitant medications?

ND

Yes No

CONFIDENTIAL

page 17 of 101

Product: ABC123 CRF Version: 1.0 Protocol ID: ABC-01

Sponsor: MAMA Pharm. Subject ID Subject Initials A B C

Screening ID A B C S

Period 1 (-1D~2D) / 2D

Visit Date Date

y

y

y

y

Laboratory Test - Blood Date and time

y

Type of test

y

m

d

d

* Value: EMR export

y

y

m

m

d

d

Hematology

Laboratory Test - Urine Date and time

m

y

y

H

H

ND

M

M

Coagulation

Chemistry

* Value: EMR export

y

y

m

m

d

d

H

H

ND

M

M

12-lead ECG Date and time

ND

y

y

y

y

m

Ventricular rate

bpm

PR interval

msec

QRS

msec

QT

msec

QTc

msec

Clinically significant

Serology

m

d

d

H

H

M

M

Yes No

CONFIDENTIAL

page 18 of 101

Product: ABC123 CRF Version: 1.0 Protocol ID: ABC-01

Screening ID A B C S

Period 1 (-1D~2D) / 2D

Adverse Event Check

Sponsor: MAMA Pharm. Subject ID Subject Initials A B C ND

Clinically significant findings?

Yes No

Physical Examination Check Remarkable findings?

ND

Yes No

Prior/Concomitant Medication Check Any prior/concomitant medications?

ND

Yes No

Check-out Assessment Is it okay to discharge?

Yes No

CONFIDENTIAL

page 19 of 101

Product: ABC123 CRF Version: 1.0 Protocol ID: ABC-01 Period 1 (-1D~2D) / 2D

Screening ID A B C S

Sponsor: MAMA Pharm. Subject ID Subject Initials A B C

Completed by Signature with date

Reviewed by Signature with date

CONFIDENTIAL

page 20 of 101

Period 2 (-1D~2D)

CONFIDENTIAL

page 21 of 101

Product: ABC123 CRF Version: 1.0 Protocol ID: ABC-01

Sponsor: MAMA Pharm. Subject ID Subject Initials A B C

Screening ID A B C S

Period 2 (-1D~2D) / -1D

Visit Date Date

y

y

y

y

m

m

d

d

Vital Sign

ND

Sitting position / Tympanic temperature Date and time

y

y

y

y

m

SBP

mmHg

DBP

mmHg

PR

bpm

TEMP

O

m

d

d

H

H

M

M

C

Urine Cotinine Test

ND

Pass Fail

Laboratory Test - Blood Date and time

y

Type of test

y

* Value: EMR export

y

y

CONFIDENTIAL

m

d

d

Hematology

Laboratory Test - Urine Date and time

m

y

y

H

H

ND

M

M

Coagulation

Chemistry

* Value: EMR export

y

y

m

m

d

d

H

H

Serology

ND

M

M

page 22 of 101

Product: ABC123 CRF Version: 1.0 Protocol ID: ABC-01

Sponsor: MAMA Pharm. Subject ID Subject Initials A B C

Screening ID A B C S

Period 2 (-1D~2D) / -1D

12-lead ECG Date and time

ND

y

y

y

y

m

Ventricular rate

bpm

PR interval

msec

QRS

msec

QT

msec

QTc

msec

Clinically significant

m

d

d

H

H

M

M

Yes No

Physical Examination Check Remarkable findings?

ND

Yes No

Prior/Concomitant Medication Check Any prior/concomitant medications?

ND

Yes No

Check-in Assessment Is it okay to continue to participate?

Yes No

CONFIDENTIAL

page 23 of 101

Product: ABC123 CRF Version: 1.0 Protocol ID: ABC-01 Period 2 (-1D~2D) / -1D

Screening ID A B C S

Adverse Event Check Clinically significant findings?

Sponsor: MAMA Pharm. Subject ID Subject Initials A B C ND

Yes No

CONFIDENTIAL

page 24 of 101

Product: ABC123 CRF Version: 1.0 Protocol ID: ABC-01

Sponsor: MAMA Pharm. Subject ID Subject Initials A B C

Screening ID A B C S

Period 2 (-1D~2D) / 1D

Visit Date Date

y

y

y

y

m

m

d

d

Drug Administration Was the study drug administrated to the subject?

Yes No

Start date and time

y

End time

y

y

y

m

m

d

d

(Acceptable:60+-5min)

H

H

M

M

H

H

M

M

NA

Study drug Dose

300

Unit

mg

600 Route

IV PO

CONFIDENTIAL

Fasting status

Yes No

page 25 of 101

Product: ABC123 CRF Version: 1.0 Protocol ID: ABC-01

Screening ID A B C S

Period 2 (-1D~2D) / 1D

Adverse Event Check

Sponsor: MAMA Pharm. Subject ID Subject Initials A B C ND

Clinically significant findings?

Yes No

Physical Examination Check Remarkable findings?

ND

Yes No

Prior/Concomitant Medication Check Any prior/concomitant medications?

ND

Yes No

CONFIDENTIAL

page 26 of 101

Product: ABC123 CRF Version: 1.0 Protocol ID: ABC-01

Sponsor: MAMA Pharm. Subject ID Subject Initials A B C

Screening ID A B C S

Period 2 (-1D~2D) / 2D

Visit Date Date

y

y

y

y

Laboratory Test - Blood Date and time

y

Type of test

y

m

d

d

* Value: EMR export

y

y

m

m

d

d

Hematology

Laboratory Test - Urine Date and time

m

y

y

H

H

ND

M

M

Coagulation

Chemistry

* Value: EMR export

y

y

m

m

d

d

H

H

ND

M

M

12-lead ECG Date and time

ND

y

y

y

y

m

Ventricular rate

bpm

PR interval

msec

QRS

msec

QT

msec

QTc

msec

Clinically significant

Serology

m

d

d

H

H

M

M

Yes No

CONFIDENTIAL

page 27 of 101

Product: ABC123 CRF Version: 1.0 Protocol ID: ABC-01

Screening ID A B C S

Period 2 (-1D~2D) / 2D

Adverse Event Check

Sponsor: MAMA Pharm. Subject ID Subject Initials A B C ND

Clinically significant findings?

Yes No

Physical Examination Check Remarkable findings?

ND

Yes No

Prior/Concomitant Medication Check Any prior/concomitant medications?

ND

Yes No

Check-out Assessment Is it okay to discharge?

Yes No

CONFIDENTIAL

page 28 of 101

Product: ABC123 CRF Version: 1.0 Protocol ID: ABC-01 Period 2 (-1D~2D) / 2D

Screening ID A B C S

Sponsor: MAMA Pharm. Subject ID Subject Initials A B C

Completed by Signature with date

Reviewed by Signature with date

CONFIDENTIAL

page 29 of 101

Form by Activity - IV

CONFIDENTIAL

page 30 of 101

Product: ABC123 CRF Version: 1.0 Protocol ID: ABC-01

Screening ID A B C S

Form by Activity - IV

PK sampling Nominal Time

Sponsor: MAMA Pharm. Subject ID Subject Initials A B C

IV

Route

Date

ND

Time

Acceptable

0h (Predose)

ND

-30min y

y

y

y

m

m

d

d

H

H

M

M

y

y

y

y

m

m

d

d

H

H

M

M

y

y

y

y

m

m

d

d

H

H

M

M

y

y

y

y

m

m

d

d

H

H

M

M

y

y

y

y

m

m

d

d

H

H

M

M

y

y

y

y

m

m

d

d

H

H

M

M

y

y

y

y

m

m

d

d

H

H

M

M

y

y

y

y

m

m

d

d

H

H

M

M

y

y

y

y

m

m

d

d

H

H

M

M

y

y

y

y

m

m

d

d

H

H

M

M

y

y

y

y

m

m

d

d

H

H

M

M

y

y

y

y

m

m

d

d

H

H

M

M

y

y

y

y

m

m

d

d

H

H

M

M

y

y

y

y

m

m

d

d

H

H

M

M

y

y

y

y

m

m

d

d

H

H

M

M

y

y

y

y

m

m

d

d

H

H

M

M

0.25h

+-5min 0.5h

+-5min 0.75h

+-5min 1h

+-10min 1.25h

+-5min 1.5h

+-5min 1.75h

+-5min 2h

+-5min 2.5h

+-5min 3h

+-5min 4h

+-5min 6h

+-5min 8h

+-5min 12h

+-10min 24h

+-10min

CONFIDENTIAL

page 31 of 101

Product: ABC123 CRF Version: 1.0 Protocol ID: ABC-01

Screening ID A B C S

Form by Activity - IV

Sponsor: MAMA Pharm. Subject ID Subject Initials A B C

Urine Collection

ND

Nominal Date Time

Time

Acceptable Item

0h (Predose) y

y

y

y

m

m

d

d

H

H

M

M

y

y

y

y

m

m

d

d

H

H

M

M

y

y

y

y

m

m

d

d

H

H

M

M

y

y

y

y

m

m

d

d

H

H

M

M

y

y

y

y

m

m

d

d

H

H

M

M

Value

Unit ND

-60min

Start

+-30min

End/Start

ml

+-30min

End/Start

ml

+-30min

End/Start

ml

+-30min

End

ml

4h

8h

12h

24h

CONFIDENTIAL

page 32 of 101

Product: ABC123 CRF Version: 1.0 Protocol ID: ABC-01

Screening ID A B C S

Form by Activity - IV

Sponsor: MAMA Pharm. Subject ID Subject Initials A B C

Vital Sign

ND

Sitting position / Tympanic temperature Nominal Date Time

Time

Acceptable Item

Value

Unit

ND

0h (Predose) y

y

y

y

m

m

d

d

H

H

M

M

-60min

SYSBP

mmHg

DIABP

mmHg

PULSE

bpm

TEMP

O

SYSBP

mmHg

DIABP

mmHg

PULSE

bpm

TEMP

O

SYSBP

mmHg

DIABP

mmHg

PULSE

bpm

TEMP

O

SYSBP

mmHg

DIABP

mmHg

PULSE

bpm

TEMP

O

C

4h y

y

y

y

m

m

d

d

H

H

M

M

+-30min

C

8h y

y

y

y

m

m

d

d

H

H

M

M

+-30min

C

24h y

CONFIDENTIAL

y

y

y

m

m

d

d

H

H

M

M

+-30min

C

page 33 of 101

Product: ABC123 CRF Version: 1.0 Protocol ID: ABC-01

Screening ID A B C S

Form by Activity - IV

Sponsor: MAMA Pharm. Subject ID Subject Initials A B C

Topical Tolerability Assessment Nominal Date Time

ND

Time

Acceptable

0h (Predose)

VIP score

ND

-30min y

y

y

y

m

m

d

d

H

H

M

M

y

y

y

y

m

m

d

d

H

H

M

M

y

y

y

y

m

m

d

d

H

H

M

M

y

y

y

y

m

m

d

d

H

H

M

M

y

y

y

y

m

m

d

d

H

H

M

M

1h

+15min 4h

+-10min 8h

+-10min 24h

+-30min

CONFIDENTIAL

page 34 of 101

Product: ABC123 CRF Version: 1.0 Protocol ID: ABC-01 Form by Activity - IV

Screening ID A B C S

Sponsor: MAMA Pharm. Subject ID Subject Initials A B C

Completed by Signature with date

Reviewed by Signature with date

CONFIDENTIAL

page 35 of 101

Form by Activity - PO

CONFIDENTIAL

page 36 of 101

Product: ABC123 CRF Version: 1.0 Protocol ID: ABC-01

Screening ID A B C S

Form by Activity - PO

PK sampling Nominal Time

Sponsor: MAMA Pharm. Subject ID Subject Initials A B C

PO

Route

Date

ND

Time

Acceptable

0h (Predose)

ND

-30min y

y

y

y

m

m

d

d

H

H

M

M

y

y

y

y

m

m

d

d

H

H

M

M

y

y

y

y

m

m

d

d

H

H

M

M

y

y

y

y

m

m

d

d

H

H

M

M

y

y

y

y

m

m

d

d

H

H

M

M

y

y

y

y

m

m

d

d

H

H

M

M

y

y

y

y

m

m

d

d

H

H

M

M

y

y

y

y

m

m

d

d

H

H

M

M

y

y

y

y

m

m

d

d

H

H

M

M

y

y

y

y

m

m

d

d

H

H

M

M

y

y

y

y

m

m

d

d

H

H

M

M

y

y

y

y

m

m

d

d

H

H

M

M

y

y

y

y

m

m

d

d

H

H

M

M

y

y

y

y

m

m

d

d

H

H

M

M

0.25h

+-5min 0.5h

+-5min 0.75h

+-5min 1h

+-5min 1.5h

+-5min 2h

+-5min 2.5h

+-5min 3h

+-5min 4h

+-5min 6h

+-5min 8h

+-5min 10h

+-10min 24h

+-10min

CONFIDENTIAL

page 37 of 101

Product: ABC123 CRF Version: 1.0 Protocol ID: ABC-01

Screening ID A B C S

Form by Activity - PO

Sponsor: MAMA Pharm. Subject ID Subject Initials A B C

Urine Collection

ND

Nominal Date Time

Time

Acceptable Item

0h (Predose) y

y

y

y

m

m

d

d

H

H

M

M

y

y

y

y

m

m

d

d

H

H

M

M

y

y

y

y

m

m

d

d

H

H

M

M

y

y

y

y

m

m

d

d

H

H

M

M

y

y

y

y

m

m

d

d

H

H

M

M

Value

Unit ND

-60min

Start

+-30min

End/Start

ml

+-30min

End/Start

ml

+-30min

End/Start

ml

+-30min

End

ml

4h

8h

12h

24h

CONFIDENTIAL

page 38 of 101

Product: ABC123 CRF Version: 1.0 Protocol ID: ABC-01

Screening ID A B C S

Form by Activity - PO

Sponsor: MAMA Pharm. Subject ID Subject Initials A B C

Vital Sign

ND

Sitting position / Tympanic temperature Nominal Date Time

Time

Acceptable Item

Value

Unit

ND

0h (Predose) y

y

y

y

m

m

d

d

H

H

M

M

-60min

SBP

mmHg

DBP

mmHg

PR

bpm

TEMP

O

SBP

mmHg

DBP

mmHg

PR

bpm

TEMP

O

SBP

mmHg

DBP

mmHg

PR

bpm

TEMP

O

SBP

mmHg

DBP

mmHg

PR

bpm

TEMP

O

C

4h y

y

y

y

m

m

d

d

H

H

M

M

+-30min

C

8h y

y

y

y

m

m

d

d

H

H

M

M

+-30min

C

24h y

CONFIDENTIAL

y

y

y

m

m

d

d

H

H

M

M

+-30min

C

page 39 of 101

Product: ABC123 CRF Version: 1.0 Protocol ID: ABC-01 Form by Activity - PO

Screening ID A B C S

Sponsor: MAMA Pharm. Subject ID Subject Initials A B C

Completed by Signature with date

Reviewed by Signature with date

CONFIDENTIAL

page 40 of 101

Follow-up Visit (Period 2 8D+-1D)

CONFIDENTIAL

page 41 of 101

Product: ABC123 CRF Version: 1.0 Protocol ID: ABC-01

Sponsor: MAMA Pharm. Subject ID Subject Initials A B C

Screening ID A B C S

Follow-up Visit (Period 2 8D+-1D)

Visit Date Date

y

y

y

y

m

m

d

d

Vital Sign

ND

Sitting position / Tympanic temperature Date and time

y

y

y

y

m

SBP

mmHg

DBP

mmHg

PR

bpm

TEMP

O

y

Type of test

CONFIDENTIAL

d

H

H

M

M

y

* Value: EMR export

y

y

m

m

d

d

Hematology

Laboratory Test - Urine Date and time

d

C

Laboratory Test - Blood Date and time

m

y

y

H

H

ND

M

M

Coagulation

Chemistry

* Value: EMR export

y

y

m

m

d

d

H

H

Serology

ND

M

M

page 42 of 101

Product: ABC123 CRF Version: 1.0 Protocol ID: ABC-01

Sponsor: MAMA Pharm. Subject ID Subject Initials A B C

Screening ID A B C S

Follow-up Visit (Period 2 8D+-1D)

12-lead ECG Date and time

ND

y

y

y

y

m

Ventricular rate

bpm

PR interval

msec

QRS

msec

QT

msec

QTc

msec

Clinically significant

m

d

d

H

H

M

M

Yes No

Adverse Event Check

ND

Clinically significant findings?

Yes No

Physical Examination Check Remarkable findings?

ND

Yes No

Prior/Concomitant Medication Check Any prior/concomitant medications?

ND

Yes No

CONFIDENTIAL

page 43 of 101

Product: ABC123 CRF Version: 1.0 Protocol ID: ABC-01 Follow-up Visit (Period 2 8D+-1D)

Screening ID A B C S

Sponsor: MAMA Pharm. Subject ID Subject Initials A B C

Completed by Signature with date

Reviewed by Signature with date

CONFIDENTIAL

page 44 of 101

Unscheduled Activity

CONFIDENTIAL

page 45 of 101

Product: ABC123 CRF Version: 1.0 Protocol ID: ABC-01

Sponsor: MAMA Pharm. Subject ID Subject Initials A B C

Screening ID A B C S

Unscheduled Activity

Vital Sign

ND

Sitting position / Tympanic temperature Date and time

y

y

y

y

m

SBP

mmHg

DBP

mmHg

PR

bpm

TEMP

O

Reason

m

d

d

H

H

M

M

C

AE follow-up: AE No. to assess trend Others - Duplicate blank form if necessary

Completed by Signature with date

CONFIDENTIAL

page 46 of 101

Product: ABC123 CRF Version: 1.0 Protocol ID: ABC-01

Sponsor: MAMA Pharm. Subject ID Subject Initials A B C

Screening ID A B C S

Unscheduled Activity

Vital Sign

ND

Sitting position / Tympanic temperature Date and time

y

y

y

y

m

SBP

mmHg

DBP

mmHg

PR

bpm

TEMP

O

Reason

m

d

d

H

H

M

M

C

AE follow-up: AE No. to assess trend Others - Duplicate blank form if necessary

Completed by Signature with date

CONFIDENTIAL

page 47 of 101

Product: ABC123 CRF Version: 1.0 Protocol ID: ABC-01

Sponsor: MAMA Pharm. Subject ID Subject Initials A B C

Screening ID A B C S

Unscheduled Activity

Vital Sign

ND

Sitting position / Tympanic temperature Date and time

y

y

y

y

m

SBP

mmHg

DBP

mmHg

PR

bpm

TEMP

O

Reason

m

d

d

H

H

M

M

C

AE follow-up: AE No. to assess trend Others - Duplicate blank form if necessary

Completed by Signature with date

CONFIDENTIAL

page 48 of 101

Product: ABC123 CRF Version: 1.0 Protocol ID: ABC-01

Sponsor: MAMA Pharm. Subject ID Subject Initials A B C

Screening ID A B C S

Unscheduled Activity

Vital Sign

ND

Sitting position / Tympanic temperature Date and time

y

y

y

y

m

SBP

mmHg

DBP

mmHg

PR

bpm

TEMP

O

Reason

m

d

d

H

H

M

M

C

AE follow-up: AE No. to assess trend Others - Duplicate blank form if necessary

Completed by Signature with date

CONFIDENTIAL

page 49 of 101

Product: ABC123 CRF Version: 1.0 Protocol ID: ABC-01

Sponsor: MAMA Pharm. Subject ID Subject Initials A B C

Screening ID A B C S

Unscheduled Activity

Vital Sign

ND

Sitting position / Tympanic temperature Date and time

y

y

y

y

m

SBP

mmHg

DBP

mmHg

PR

bpm

TEMP

O

Reason

m

d

d

H

H

M

M

C

AE follow-up: AE No. to assess trend Others - Duplicate blank form if necessary

Completed by Signature with date

CONFIDENTIAL

page 50 of 101

Product: ABC123 CRF Version: 1.0 Protocol ID: ABC-01

Screening ID A B C S

Unscheduled Activity

Laboratory Test - Blood Date and time

Sponsor: MAMA Pharm. Subject ID Subject Initials A B C

y

y

* Value: EMR export

y

y

m

m

d

d

H

Type of test

Hematology

Reason

AE follow-up: AE No.

H

ND

M

Coagulation

M

Chemistry

Serology

to assess trend Others - Duplicate blank form if necessary

Completed by Signature with date

CONFIDENTIAL

page 51 of 101

Product: ABC123 CRF Version: 1.0 Protocol ID: ABC-01

Screening ID A B C S

Unscheduled Activity

Laboratory Test - Blood Date and time

Sponsor: MAMA Pharm. Subject ID Subject Initials A B C

y

y

* Value: EMR export

y

y

m

m

d

d

H

Type of test

Hematology

Reason

AE follow-up: AE No.

H

ND

M

Coagulation

M

Chemistry

Serology

to assess trend Others - Duplicate blank form if necessary

Completed by Signature with date

CONFIDENTIAL

page 52 of 101

Product: ABC123 CRF Version: 1.0 Protocol ID: ABC-01

Screening ID A B C S

Unscheduled Activity

Laboratory Test - Blood Date and time

Sponsor: MAMA Pharm. Subject ID Subject Initials A B C

y

y

* Value: EMR export

y

y

m

m

d

d

H

Type of test

Hematology

Reason

AE follow-up: AE No.

H

ND

M

Coagulation

M

Chemistry

Serology

to assess trend Others - Duplicate blank form if necessary

Completed by Signature with date

CONFIDENTIAL

page 53 of 101

Product: ABC123 CRF Version: 1.0 Protocol ID: ABC-01

Screening ID A B C S

Unscheduled Activity

Laboratory Test - Blood Date and time

Sponsor: MAMA Pharm. Subject ID Subject Initials A B C

y

y

* Value: EMR export

y

y

m

m

d

d

H

Type of test

Hematology

Reason

AE follow-up: AE No.

H

ND

M

Coagulation

M

Chemistry

Serology

to assess trend Others - Duplicate blank form if necessary

Completed by Signature with date

CONFIDENTIAL

page 54 of 101

Product: ABC123 CRF Version: 1.0 Protocol ID: ABC-01

Screening ID A B C S

Unscheduled Activity

Laboratory Test - Blood Date and time

Sponsor: MAMA Pharm. Subject ID Subject Initials A B C

y

y

* Value: EMR export

y

y

m

m

d

d

H

Type of test

Hematology

Reason

AE follow-up: AE No.

H

ND

M

Coagulation

M

Chemistry

Serology

to assess trend Others - Duplicate blank form if necessary

Completed by Signature with date

CONFIDENTIAL

page 55 of 101

Product: ABC123 CRF Version: 1.0 Protocol ID: ABC-01

Screening ID A B C S

Unscheduled Activity

Laboratory Test - Urine Date and time Reason

Sponsor: MAMA Pharm. Subject ID Subject Initials A B C

y

y

* Value: EMR export

y

y

m

m

d

d

H

H

ND

M

M

AE follow-up: AE No. to assess trend Others - Duplicate blank form if necessary

Completed by Signature with date

CONFIDENTIAL

page 56 of 101

Product: ABC123 CRF Version: 1.0 Protocol ID: ABC-01

Screening ID A B C S

Unscheduled Activity

Laboratory Test - Urine Date and time Reason

Sponsor: MAMA Pharm. Subject ID Subject Initials A B C

y

y

* Value: EMR export

y

y

m

m

d

d

H

H

ND

M

M

AE follow-up: AE No. to assess trend Others - Duplicate blank form if necessary

Completed by Signature with date

CONFIDENTIAL

page 57 of 101

Product: ABC123 CRF Version: 1.0 Protocol ID: ABC-01

Screening ID A B C S

Unscheduled Activity

Laboratory Test - Urine Date and time Reason

Sponsor: MAMA Pharm. Subject ID Subject Initials A B C

y

y

* Value: EMR export

y

y

m

m

d

d

H

H

ND

M

M

AE follow-up: AE No. to assess trend Others - Duplicate blank form if necessary

Completed by Signature with date

CONFIDENTIAL

page 58 of 101

Product: ABC123 CRF Version: 1.0 Protocol ID: ABC-01

Screening ID A B C S

Unscheduled Activity

Laboratory Test - Urine Date and time Reason

Sponsor: MAMA Pharm. Subject ID Subject Initials A B C

y

y

* Value: EMR export

y

y

m

m

d

d

H

H

ND

M

M

AE follow-up: AE No. to assess trend Others - Duplicate blank form if necessary

Completed by Signature with date

CONFIDENTIAL

page 59 of 101

Product: ABC123 CRF Version: 1.0 Protocol ID: ABC-01

Screening ID A B C S

Unscheduled Activity

Laboratory Test - Urine Date and time Reason

Sponsor: MAMA Pharm. Subject ID Subject Initials A B C

y

y

* Value: EMR export

y

y

m

m

d

d

H

H

ND

M

M

AE follow-up: AE No. to assess trend Others - Duplicate blank form if necessary

Completed by Signature with date

CONFIDENTIAL

page 60 of 101

Product: ABC123 CRF Version: 1.0 Protocol ID: ABC-01

Sponsor: MAMA Pharm. Subject ID Subject Initials A B C

Screening ID A B C S

Unscheduled Activity

12-lead ECG Date and time

ND

y

y

y

y

m

Ventricular rate

bpm

PR interval

msec

QRS

msec

QT

msec

QTc

msec

Clinically significant

m

d

d

H

H

M

M

Yes No

Reason

AE follow-up: AE No. to assess trend Others - Duplicate blank form if necessary

Completed by Signature with date

CONFIDENTIAL

page 61 of 101

Product: ABC123 CRF Version: 1.0 Protocol ID: ABC-01

Sponsor: MAMA Pharm. Subject ID Subject Initials A B C

Screening ID A B C S

Unscheduled Activity

12-lead ECG Date and time

ND

y

y

y

y

m

Ventricular rate

bpm

PR interval

msec

QRS

msec

QT

msec

QTc

msec

Clinically significant

m

d

d

H

H

M

M

Yes No

Reason

AE follow-up: AE No. to assess trend Others - Duplicate blank form if necessary

Completed by Signature with date

CONFIDENTIAL

page 62 of 101

Product: ABC123 CRF Version: 1.0 Protocol ID: ABC-01

Sponsor: MAMA Pharm. Subject ID Subject Initials A B C

Screening ID A B C S

Unscheduled Activity

12-lead ECG Date and time

ND

y

y

y

y

m

Ventricular rate

bpm

PR interval

msec

QRS

msec

QT

msec

QTc

msec

Clinically significant

m

d

d

H

H

M

M

Yes No

Reason

AE follow-up: AE No. to assess trend Others - Duplicate blank form if necessary

Completed by Signature with date

CONFIDENTIAL

page 63 of 101

Product: ABC123 CRF Version: 1.0 Protocol ID: ABC-01

Sponsor: MAMA Pharm. Subject ID Subject Initials A B C

Screening ID A B C S

Unscheduled Activity

12-lead ECG Date and time

ND

y

y

y

y

m

Ventricular rate

bpm

PR interval

msec

QRS

msec

QT

msec

QTc

msec

Clinically significant

m

d

d

H

H

M

M

Yes No

Reason

AE follow-up: AE No. to assess trend Others - Duplicate blank form if necessary

Completed by Signature with date

CONFIDENTIAL

page 64 of 101

Product: ABC123 CRF Version: 1.0 Protocol ID: ABC-01

Sponsor: MAMA Pharm. Subject ID Subject Initials A B C

Screening ID A B C S

Unscheduled Activity

12-lead ECG Date and time

ND

y

y

y

y

m

Ventricular rate

bpm

PR interval

msec

QRS

msec

QT

msec

QTc

msec

Clinically significant

m

d

d

H

H

M

M

Yes No

Reason

AE follow-up: AE No. to assess trend Others - Duplicate blank form if necessary

Completed by Signature with date

CONFIDENTIAL

page 65 of 101

Product: ABC123 CRF Version: 1.0 Protocol ID: ABC-01

Screening ID A B C S

Unscheduled Activity

Other Test

ND

Date

y

y

Time

y

y

m

Sponsor: MAMA Pharm. Subject ID Subject Initials A B C

m

d

d

H

H

Item

M

M

Description

Reason

AE follow-up: AE No. to assess trend Others - Duplicate blank form if necessary

Completed by Signature with date

CONFIDENTIAL

page 66 of 101

Product: ABC123 CRF Version: 1.0 Protocol ID: ABC-01

Screening ID A B C S

Unscheduled Activity

Other Test

ND

Date

y

y

Time

y

y

m

Sponsor: MAMA Pharm. Subject ID Subject Initials A B C

m

d

d

H

H

Item

M

M

Description

Reason

AE follow-up: AE No. to assess trend Others - Duplicate blank form if necessary

Completed by Signature with date

CONFIDENTIAL

page 67 of 101

Product: ABC123 CRF Version: 1.0 Protocol ID: ABC-01

Screening ID A B C S

Unscheduled Activity

Other Test

ND

Date

y

y

Time

y

y

m

Sponsor: MAMA Pharm. Subject ID Subject Initials A B C

m

d

d

H

H

Item

M

M

Description

Reason

AE follow-up: AE No. to assess trend Others - Duplicate blank form if necessary

Completed by Signature with date

CONFIDENTIAL

page 68 of 101

Product: ABC123 CRF Version: 1.0 Protocol ID: ABC-01

Screening ID A B C S

Unscheduled Activity

Other Test

ND

Date

y

y

Time

y

y

m

Sponsor: MAMA Pharm. Subject ID Subject Initials A B C

m

d

d

H

H

Item

M

M

Description

Reason

AE follow-up: AE No. to assess trend Others - Duplicate blank form if necessary

Completed by Signature with date

CONFIDENTIAL

page 69 of 101

Product: ABC123 CRF Version: 1.0 Protocol ID: ABC-01

Screening ID A B C S

Unscheduled Activity

Other Test

ND

Date

y

y

Time

y

y

m

Sponsor: MAMA Pharm. Subject ID Subject Initials A B C

m

d

d

H

H

Item

M

M

Description

Reason

AE follow-up: AE No. to assess trend Others - Duplicate blank form if necessary

Completed by Signature with date

CONFIDENTIAL

page 70 of 101

Product: ABC123 CRF Version: 1.0 Protocol ID: ABC-01

Screening ID A B C S

Unscheduled Activity

Sponsor: MAMA Pharm. Subject ID Subject Initials A B C

AE/PE/CM Check Date

y

Reason

y

y

y

m

m

d

d

AE follow-up: AE No. to assess trend Others

Adverse Event Check

ND

Clinically significant findings?

Yes No

Physical Examination Check Remarkable findings?

ND

Yes No

Prior/Concomitant Medication Check Any prior/concomitant medications?

ND

Yes No - Duplicate blank form if necessary

Completed by Signature with date

CONFIDENTIAL

page 71 of 101

Product: ABC123 CRF Version: 1.0 Protocol ID: ABC-01

Screening ID A B C S

Unscheduled Activity

Sponsor: MAMA Pharm. Subject ID Subject Initials A B C

AE/PE/CM Check Date

y

Reason

y

y

y

m

m

d

d

AE follow-up: AE No. to assess trend Others

Adverse Event Check

ND

Clinically significant findings?

Yes No

Physical Examination Check Remarkable findings?

ND

Yes No

Prior/Concomitant Medication Check Any prior/concomitant medications?

ND

Yes No - Duplicate blank form if necessary

Completed by Signature with date

CONFIDENTIAL

page 72 of 101

Product: ABC123 CRF Version: 1.0 Protocol ID: ABC-01

Screening ID A B C S

Unscheduled Activity

Sponsor: MAMA Pharm. Subject ID Subject Initials A B C

AE/PE/CM Check Date

y

Reason

y

y

y

m

m

d

d

AE follow-up: AE No. to assess trend Others

Adverse Event Check

ND

Clinically significant findings?

Yes No

Physical Examination Check Remarkable findings?

ND

Yes No

Prior/Concomitant Medication Check Any prior/concomitant medications?

ND

Yes No - Duplicate blank form if necessary

Completed by Signature with date

CONFIDENTIAL

page 73 of 101

Product: ABC123 CRF Version: 1.0 Protocol ID: ABC-01

Screening ID A B C S

Unscheduled Activity

Sponsor: MAMA Pharm. Subject ID Subject Initials A B C

AE/PE/CM Check Date

y

Reason

y

y

y

m

m

d

d

AE follow-up: AE No. to assess trend Others

Adverse Event Check

ND

Clinically significant findings?

Yes No

Physical Examination Check Remarkable findings?

ND

Yes No

Prior/Concomitant Medication Check Any prior/concomitant medications?

ND

Yes No - Duplicate blank form if necessary

Completed by Signature with date

CONFIDENTIAL

page 74 of 101

Product: ABC123 CRF Version: 1.0 Protocol ID: ABC-01

Screening ID A B C S

Unscheduled Activity

Sponsor: MAMA Pharm. Subject ID Subject Initials A B C

AE/PE/CM Check Date

y

Reason

y

y

y

m

m

d

d

AE follow-up: AE No. to assess trend Others

Adverse Event Check

ND

Clinically significant findings?

Yes No

Physical Examination Check Remarkable findings?

ND

Yes No

Prior/Concomitant Medication Check Any prior/concomitant medications?

ND

Yes No - Duplicate blank form if necessary

Completed by Signature with date

CONFIDENTIAL

page 75 of 101

Product: ABC123 CRF Version: 1.0 Protocol ID: ABC-01 Unscheduled Activity

Screening ID A B C S

Sponsor: MAMA Pharm. Subject ID Subject Initials A B C

Reviewed by Signature with date

CONFIDENTIAL

page 76 of 101

Event

CONFIDENTIAL

page 77 of 101

Product: ABC123 CRF Version: 1.0 Protocol ID: ABC-01

Screening ID A B C S

Event

Sponsor: MAMA Pharm. Subject ID Subject Initials A B C

Physical Examination Date

System*

Description

Progress

AE No.

New y

y

y

y

m

m

d

d

Recovering

NA

Aggravating No change Recovered

* System: 01= Blood and lymphatic system disorders 02= Cardiac disorders

15= Musculoskeletal and connective tissue disorders

03= Congenital, familial and genetic disorders

16= Neoplasms benign, malignant and unspecified (incl cysts and polyps)

04= Ear and labyrinth disorders

17= Nervous system disorders

05= Endocrine disorders

18= Pregnancy, puerperium and perinatal conditions

06= Eye disorders

19= Product issues

07= Gastrointestinal disorders 08= General disorders and administration site conditions

20= Psychiatric disorders 21= Renal and urinary disorders

09= Hepatobiliary disorders

22= Reproductive system and breast disorders

10= Immune system disorders

23= Respiratory, thoracic and mediastinal disorders

11= Infections and infestations

24= Skin and subcutaneous tissue disorders

12= Injury, poisoning and procedural complications

25= Social circumstances

13= Investigations 14= Metabolism and nutrition disorders

26= Surgical and medical procedures 27= Vascular disorders

- Duplicate blank form if necessary

Completed by Signature with date

CONFIDENTIAL

page 78 of 101

Product: ABC123 CRF Version: 1.0 Protocol ID: ABC-01

Screening ID A B C S

Event

Sponsor: MAMA Pharm. Subject ID Subject Initials A B C

Physical Examination Date

System*

Description

Progress

AE No.

New y

y

y

y

m

m

d

d

Recovering

NA

Aggravating No change Recovered

* System: 01= Blood and lymphatic system disorders 02= Cardiac disorders

15= Musculoskeletal and connective tissue disorders

03= Congenital, familial and genetic disorders

16= Neoplasms benign, malignant and unspecified (incl cysts and polyps)

04= Ear and labyrinth disorders

17= Nervous system disorders

05= Endocrine disorders

18= Pregnancy, puerperium and perinatal conditions

06= Eye disorders

19= Product issues

07= Gastrointestinal disorders 08= General disorders and administration site conditions

20= Psychiatric disorders 21= Renal and urinary disorders

09= Hepatobiliary disorders

22= Reproductive system and breast disorders

10= Immune system disorders

23= Respiratory, thoracic and mediastinal disorders

11= Infections and infestations

24= Skin and subcutaneous tissue disorders

12= Injury, poisoning and procedural complications

25= Social circumstances

13= Investigations 14= Metabolism and nutrition disorders

26= Surgical and medical procedures 27= Vascular disorders

- Duplicate blank form if necessary

Completed by Signature with date

CONFIDENTIAL

page 79 of 101

Product: ABC123 CRF Version: 1.0 Protocol ID: ABC-01

Screening ID A B C S

Event

Sponsor: MAMA Pharm. Subject ID Subject Initials A B C

Physical Examination Date

System*

Description

Progress

AE No.

New y

y

y

y

m

m

d

d

Recovering

NA

Aggravating No change Recovered

* System: 01= Blood and lymphatic system disorders 02= Cardiac disorders

15= Musculoskeletal and connective tissue disorders

03= Congenital, familial and genetic disorders

16= Neoplasms benign, malignant and unspecified (incl cysts and polyps)

04= Ear and labyrinth disorders

17= Nervous system disorders

05= Endocrine disorders

18= Pregnancy, puerperium and perinatal conditions

06= Eye disorders

19= Product issues

07= Gastrointestinal disorders 08= General disorders and administration site conditions

20= Psychiatric disorders 21= Renal and urinary disorders

09= Hepatobiliary disorders

22= Reproductive system and breast disorders

10= Immune system disorders

23= Respiratory, thoracic and mediastinal disorders

11= Infections and infestations

24= Skin and subcutaneous tissue disorders

12= Injury, poisoning and procedural complications

25= Social circumstances

13= Investigations 14= Metabolism and nutrition disorders

26= Surgical and medical procedures 27= Vascular disorders

- Duplicate blank form if necessary

Completed by Signature with date

CONFIDENTIAL

page 80 of 101

Product: ABC123 CRF Version: 1.0 Protocol ID: ABC-01

Screening ID A B C S

Event

Sponsor: MAMA Pharm. Subject ID Subject Initials A B C

Physical Examination Date

System*

Description

Progress

AE No.

New y

y

y

y

m

m

d

d

Recovering

NA

Aggravating No change Recovered

* System: 01= Blood and lymphatic system disorders 02= Cardiac disorders

15= Musculoskeletal and connective tissue disorders

03= Congenital, familial and genetic disorders

16= Neoplasms benign, malignant and unspecified (incl cysts and polyps)

04= Ear and labyrinth disorders

17= Nervous system disorders

05= Endocrine disorders

18= Pregnancy, puerperium and perinatal conditions

06= Eye disorders

19= Product issues

07= Gastrointestinal disorders 08= General disorders and administration site conditions

20= Psychiatric disorders 21= Renal and urinary disorders

09= Hepatobiliary disorders

22= Reproductive system and breast disorders

10= Immune system disorders

23= Respiratory, thoracic and mediastinal disorders

11= Infections and infestations

24= Skin and subcutaneous tissue disorders

12= Injury, poisoning and procedural complications

25= Social circumstances

13= Investigations 14= Metabolism and nutrition disorders

26= Surgical and medical procedures 27= Vascular disorders

- Duplicate blank form if necessary

Completed by Signature with date

CONFIDENTIAL

page 81 of 101

Product: ABC123 CRF Version: 1.0 Protocol ID: ABC-01

Screening ID A B C S

Event

Sponsor: MAMA Pharm. Subject ID Subject Initials A B C

Physical Examination Date

System*

Description

Progress

AE No.

New y

y

y

y

m

m

d

d

Recovering

NA

Aggravating No change Recovered

* System: 01= Blood and lymphatic system disorders 02= Cardiac disorders

15= Musculoskeletal and connective tissue disorders

03= Congenital, familial and genetic disorders

16= Neoplasms benign, malignant and unspecified (incl cysts and polyps)

04= Ear and labyrinth disorders

17= Nervous system disorders

05= Endocrine disorders

18= Pregnancy, puerperium and perinatal conditions

06= Eye disorders

19= Product issues

07= Gastrointestinal disorders 08= General disorders and administration site conditions

20= Psychiatric disorders 21= Renal and urinary disorders

09= Hepatobiliary disorders

22= Reproductive system and breast disorders

10= Immune system disorders

23= Respiratory, thoracic and mediastinal disorders

11= Infections and infestations

24= Skin and subcutaneous tissue disorders

12= Injury, poisoning and procedural complications

25= Social circumstances

13= Investigations 14= Metabolism and nutrition disorders

26= Surgical and medical procedures 27= Vascular disorders

- Duplicate blank form if necessary

Completed by Signature with date

CONFIDENTIAL

page 82 of 101

Product: ABC123 CRF Version: 1.0 Protocol ID: ABC-01

Sponsor: MAMA Pharm. Subject ID Subject Initials A B C

Screening ID A B C S

Event

Adverse Event AE No. Adverse event term Start date and time End date and time

Severity

y

y

y

y

m

m

d

d

H

H

M

M

y

y

y

y

m

m

d

d

H

H

M

M

Mild

Toxicity Grade

Ongoing

1

Moderate

2

Severe

3 4 5 Not Applicable

Serious Event

Yes

Drug Therapy Given

No Relationship

Outcome

Yes No

Definite

Action Taken with

Dose increased

Probable

Investigational Product

Dose not changed

Possible

Dose reduced

Unlikely

Drug interrupted

Definitely Not

Drug withdrawn

Unassessable

Not applicable

Recovered/Resolved Recovered/Resolved with sequelae

Dropped from Study

Yes No

Recovering/Resolving Not Recovered/Not Resolved Fatal Unknown Comment

CONFIDENTIAL

page 83 of 101

Product: ABC123 CRF Version: 1.0 Protocol ID: ABC-01 Event

Screening ID A B C S

Sponsor: MAMA Pharm. Subject ID Subject Initials A B C

Adverse Event(Cont.) MedDRA Coding

Term

Code

Lowest Level Term

Preferred Term

High Level Term

High Level Group Term

Primary System Organ Class

- Duplicate blank form if necessary

Completed by Signature with date

CONFIDENTIAL

page 84 of 101

Product: ABC123 CRF Version: 1.0 Protocol ID: ABC-01

Sponsor: MAMA Pharm. Subject ID Subject Initials A B C

Screening ID A B C S

Event

Adverse Event AE No. Adverse event term Start date and time End date and time

Severity

y

y

y

y

m

m

d

d

H

H

M

M

y

y

y

y

m

m

d

d

H

H

M

M

Mild

Toxicity Grade

Ongoing

1

Moderate

2

Severe

3 4 5 Not Applicable

Serious Event

Yes

Drug Therapy Given

No Relationship

Outcome

Yes No

Definite

Action Taken with

Dose increased

Probable

Investigational Product

Dose not changed

Possible

Dose reduced

Unlikely

Drug interrupted

Definitely Not

Drug withdrawn

Unassessable

Not applicable

Recovered/Resolved Recovered/Resolved with sequelae

Dropped from Study

Yes No

Recovering/Resolving Not Recovered/Not Resolved Fatal Unknown Comment

CONFIDENTIAL

page 85 of 101

Product: ABC123 CRF Version: 1.0 Protocol ID: ABC-01 Event

Screening ID A B C S

Sponsor: MAMA Pharm. Subject ID Subject Initials A B C

Adverse Event(Cont.) MedDRA Coding

Term

Code

Lowest Level Term

Preferred Term

High Level Term

High Level Group Term

Primary System Organ Class

- Duplicate blank form if necessary

Completed by Signature with date

CONFIDENTIAL

page 86 of 101

Product: ABC123 CRF Version: 1.0 Protocol ID: ABC-01

Sponsor: MAMA Pharm. Subject ID Subject Initials A B C

Screening ID A B C S

Event

Adverse Event AE No. Adverse event term Start date and time End date and time

Severity

y

y

y

y

m

m

d

d

H

H

M

M

y

y

y

y

m

m

d

d

H

H

M

M

Mild

Toxicity Grade

Ongoing

1

Moderate

2

Severe

3 4 5 Not Applicable

Serious Event

Yes

Drug Therapy Given

No Relationship

Outcome

Yes No

Definite

Action Taken with

Dose increased

Probable

Investigational Product

Dose not changed

Possible

Dose reduced

Unlikely

Drug interrupted

Definitely Not

Drug withdrawn

Unassessable

Not applicable

Recovered/Resolved Recovered/Resolved with sequelae

Dropped from Study

Yes No

Recovering/Resolving Not Recovered/Not Resolved Fatal Unknown Comment

CONFIDENTIAL

page 87 of 101

Product: ABC123 CRF Version: 1.0 Protocol ID: ABC-01 Event

Screening ID A B C S

Sponsor: MAMA Pharm. Subject ID Subject Initials A B C

Adverse Event(Cont.) MedDRA Coding

Term

Code

Lowest Level Term

Preferred Term

High Level Term

High Level Group Term

Primary System Organ Class

- Duplicate blank form if necessary

Completed by Signature with date

CONFIDENTIAL

page 88 of 101

Product: ABC123 CRF Version: 1.0 Protocol ID: ABC-01

Sponsor: MAMA Pharm. Subject ID Subject Initials A B C

Screening ID A B C S

Event

Adverse Event AE No. Adverse event term Start date and time End date and time

Severity

y

y

y

y

m

m

d

d

H

H

M

M

y

y

y

y

m

m

d

d

H

H

M

M

Mild

Toxicity Grade

Ongoing

1

Moderate

2

Severe

3 4 5 Not Applicable

Serious Event

Yes

Drug Therapy Given

No Relationship

Outcome

Yes No

Definite

Action Taken with

Dose increased

Probable

Investigational Product

Dose not changed

Possible

Dose reduced

Unlikely

Drug interrupted

Definitely Not

Drug withdrawn

Unassessable

Not applicable

Recovered/Resolved Recovered/Resolved with sequelae

Dropped from Study

Yes No

Recovering/Resolving Not Recovered/Not Resolved Fatal Unknown Comment

CONFIDENTIAL

page 89 of 101

Product: ABC123 CRF Version: 1.0 Protocol ID: ABC-01 Event

Screening ID A B C S

Sponsor: MAMA Pharm. Subject ID Subject Initials A B C

Adverse Event(Cont.) MedDRA Coding

Term

Code

Lowest Level Term

Preferred Term

High Level Term

High Level Group Term

Primary System Organ Class

- Duplicate blank form if necessary

Completed by Signature with date

CONFIDENTIAL

page 90 of 101

Product: ABC123 CRF Version: 1.0 Protocol ID: ABC-01

Sponsor: MAMA Pharm. Subject ID Subject Initials A B C

Screening ID A B C S

Event

Adverse Event AE No. Adverse event term Start date and time End date and time

Severity

y

y

y

y

m

m

d

d

H

H

M

M

y

y

y

y

m

m

d

d

H

H

M

M

Mild

Toxicity Grade

Ongoing

1

Moderate

2

Severe

3 4 5 Not Applicable

Serious Event

Yes

Drug Therapy Given

No Relationship

Outcome

Yes No

Definite

Action Taken with

Dose increased

Probable

Investigational Product

Dose not changed

Possible

Dose reduced

Unlikely

Drug interrupted

Definitely Not

Drug withdrawn

Unassessable

Not applicable

Recovered/Resolved Recovered/Resolved with sequelae

Dropped from Study

Yes No

Recovering/Resolving Not Recovered/Not Resolved Fatal Unknown Comment

CONFIDENTIAL

page 91 of 101

Product: ABC123 CRF Version: 1.0 Protocol ID: ABC-01 Event

Screening ID A B C S

Sponsor: MAMA Pharm. Subject ID Subject Initials A B C

Adverse Event(Cont.) MedDRA Coding

Term

Code

Lowest Level Term

Preferred Term

High Level Term

High Level Group Term

Primary System Organ Class

- Duplicate blank form if necessary

Completed by Signature with date

CONFIDENTIAL

page 92 of 101

Product: ABC123 CRF Version: 1.0 Protocol ID: ABC-01

Sponsor: MAMA Pharm. Subject ID Subject Initials A B C

Screening ID A B C S

Event

Prior/Comcomitant Medication No.

Medication

Date and time

Reason*

Name

Start

AE No.

y

y

y

y

m

m

d

d

H

H

M

M

y

y

y

m

m

d

d

H

H

M

M

End Dose

Unit+ y

Route^

Freq&

Ongoing

Comment

^ Route: 01= Intralesional

06= Oral

11= Transdermal

02= Intramuscular

07= Rectal

12= Vaginal

03= Intraocular

08= Respiratory (Inhalation)

88= Other, specify in comment

04= Intraperitoneal

09= Subcutaneous

99= Unknown

05= Nasal

10= Topical

+ Unit: 01= CAPSULE

04= mg (Milligram)

07= TABLET

02= g (Gram)

05= mL (Milliliter; cm3)

08= ug (Microgram; mcg)

03= IU (IE; International Unit)

06= PUFF (Puff Dosing Unit)

88= Other, specify in comment 99= Unknown

& Freq: 01= BID (Twice per day)

04= QID (4 times per day)

07= TID (3 times per day)

02= PRN (As needed)

05= QM (Every Month; Per Month)

88= Other, specify in comment

03= QD (Daily; Per Day) * Reason:

06= QOD (Every other day)

99= Unknown

If the subject took medicine for adverse event, fill out 'Reason' to 'AE No.'. - Duplicate blank form if necessary

Completed by Signature with date CONFIDENTIAL

page 93 of 101

Product: ABC123 CRF Version: 1.0 Protocol ID: ABC-01

Sponsor: MAMA Pharm. Subject ID Subject Initials A B C

Screening ID A B C S

Event

Prior/Comcomitant Medication No.

Medication

Date and time

Reason*

Name

Start

AE No.

y

y

y

y

m

m

d

d

H

H

M

M

y

y

y

m

m

d

d

H

H

M

M

End Dose

Unit+ y

Route^

Freq&

Ongoing

Comment

^ Route: 01= Intralesional

06= Oral

11= Transdermal

02= Intramuscular

07= Rectal

12= Vaginal

03= Intraocular

08= Respiratory (Inhalation)

88= Other, specify in comment

04= Intraperitoneal

09= Subcutaneous

99= Unknown

05= Nasal

10= Topical

+ Unit: 01= CAPSULE

04= mg (Milligram)

07= TABLET

02= g (Gram)

05= mL (Milliliter; cm3)

08= ug (Microgram; mcg)

03= IU (IE; International Unit)

06= PUFF (Puff Dosing Unit)

88= Other, specify in comment 99= Unknown

& Freq: 01= BID (Twice per day)

04= QID (4 times per day)

07= TID (3 times per day)

02= PRN (As needed)

05= QM (Every Month; Per Month)

88= Other, specify in comment

03= QD (Daily; Per Day) * Reason:

06= QOD (Every other day)

99= Unknown

If the subject took medicine for adverse event, fill out 'Reason' to 'AE No.'. - Duplicate blank form if necessary

Completed by Signature with date CONFIDENTIAL

page 94 of 101

Product: ABC123 CRF Version: 1.0 Protocol ID: ABC-01

Sponsor: MAMA Pharm. Subject ID Subject Initials A B C

Screening ID A B C S

Event

Prior/Comcomitant Medication No.

Medication

Date and time

Reason*

Name

Start

AE No.

y

y

y

y

m

m

d

d

H

H

M

M

y

y

y

m

m

d

d

H

H

M

M

End Dose

Unit+ y

Route^

Freq&

Ongoing

Comment

^ Route: 01= Intralesional

06= Oral

11= Transdermal

02= Intramuscular

07= Rectal

12= Vaginal

03= Intraocular

08= Respiratory (Inhalation)

88= Other, specify in comment

04= Intraperitoneal

09= Subcutaneous

99= Unknown

05= Nasal

10= Topical

+ Unit: 01= CAPSULE

04= mg (Milligram)

07= TABLET

02= g (Gram)

05= mL (Milliliter; cm3)

08= ug (Microgram; mcg)

03= IU (IE; International Unit)

06= PUFF (Puff Dosing Unit)

88= Other, specify in comment 99= Unknown

& Freq: 01= BID (Twice per day)

04= QID (4 times per day)

07= TID (3 times per day)

02= PRN (As needed)

05= QM (Every Month; Per Month)

88= Other, specify in comment

03= QD (Daily; Per Day) * Reason:

06= QOD (Every other day)

99= Unknown

If the subject took medicine for adverse event, fill out 'Reason' to 'AE No.'. - Duplicate blank form if necessary

Completed by Signature with date CONFIDENTIAL

page 95 of 101

Product: ABC123 CRF Version: 1.0 Protocol ID: ABC-01

Sponsor: MAMA Pharm. Subject ID Subject Initials A B C

Screening ID A B C S

Event

Prior/Comcomitant Medication No.

Medication

Date and time

Reason*

Name

Start

AE No.

y

y

y

y

m

m

d

d

H

H

M

M

y

y

y

m

m

d

d

H

H

M

M

End Dose

Unit+ y

Route^

Freq&

Ongoing

Comment

^ Route: 01= Intralesional

06= Oral

11= Transdermal

02= Intramuscular

07= Rectal

12= Vaginal

03= Intraocular

08= Respiratory (Inhalation)

88= Other, specify in comment

04= Intraperitoneal

09= Subcutaneous

99= Unknown

05= Nasal

10= Topical

+ Unit: 01= CAPSULE

04= mg (Milligram)

07= TABLET

02= g (Gram)

05= mL (Milliliter; cm3)

08= ug (Microgram; mcg)

03= IU (IE; International Unit)

06= PUFF (Puff Dosing Unit)

88= Other, specify in comment 99= Unknown

& Freq: 01= BID (Twice per day)

04= QID (4 times per day)

07= TID (3 times per day)

02= PRN (As needed)

05= QM (Every Month; Per Month)

88= Other, specify in comment

03= QD (Daily; Per Day) * Reason:

06= QOD (Every other day)

99= Unknown

If the subject took medicine for adverse event, fill out 'Reason' to 'AE No.'. - Duplicate blank form if necessary

Completed by Signature with date CONFIDENTIAL

page 96 of 101

Product: ABC123 CRF Version: 1.0 Protocol ID: ABC-01

Sponsor: MAMA Pharm. Subject ID Subject Initials A B C

Screening ID A B C S

Event

Prior/Comcomitant Medication No.

Medication

Date and time

Reason*

Name

Start

AE No.

y

y

y

y

m

m

d

d

H

H

M

M

y

y

y

m

m

d

d

H

H

M

M

End Dose

Unit+ y

Route^

Freq&

Ongoing

Comment

^ Route: 01= Intralesional

06= Oral

11= Transdermal

02= Intramuscular

07= Rectal

12= Vaginal

03= Intraocular

08= Respiratory (Inhalation)

88= Other, specify in comment

04= Intraperitoneal

09= Subcutaneous

99= Unknown

05= Nasal

10= Topical

+ Unit: 01= CAPSULE

04= mg (Milligram)

07= TABLET

02= g (Gram)

05= mL (Milliliter; cm3)

08= ug (Microgram; mcg)

03= IU (IE; International Unit)

06= PUFF (Puff Dosing Unit)

88= Other, specify in comment 99= Unknown

& Freq: 01= BID (Twice per day)

04= QID (4 times per day)

07= TID (3 times per day)

02= PRN (As needed)

05= QM (Every Month; Per Month)

88= Other, specify in comment

03= QD (Daily; Per Day) * Reason:

06= QOD (Every other day)

99= Unknown

If the subject took medicine for adverse event, fill out 'Reason' to 'AE No.'. - Duplicate blank form if necessary

Completed by Signature with date CONFIDENTIAL

page 97 of 101

Product: ABC123 CRF Version: 1.0 Protocol ID: ABC-01 Event

Screening ID A B C S

Sponsor: MAMA Pharm. Subject ID Subject Initials A B C

Reviewed by Signature with date

CONFIDENTIAL

page 98 of 101

Case Conclusion

CONFIDENTIAL

page 99 of 101

Product: ABC123 CRF Version: 1.0 Protocol ID: ABC-01

Sponsor: MAMA Pharm. Subject ID Subject Initials A B C

Screening ID A B C S

Case Conclusion

End of Study Last visit date

y

y

y

y

m

m

d

d

Did the subject complete the study? Completed Dropped out before drug administration Dropped out after drug administration Primary reason NOT complete the study Consent withdrawal Adverse event, Adverse drug reaction Prohibited drug taken by subject Serious non-compliance to protocol Discontinuance request by sponsor, MFDS, IRB By the investigator’s judgment or sponsor, the subject was not suitable to continue in the study Other Date/Time of withdrawal

y

y

y

y

m

m

d

d

H

H

M

M

Comment

CONFIDENTIAL

page 100 of 101

Product: ABC123 CRF Version: 1.0 Protocol ID: ABC-01 Case Conclusion

Screening ID A B C S

Sponsor: MAMA Pharm. Subject ID Subject Initials A B C

Completed by Signature with date

Principal Investigator Statement The following statement is to be dated and signed once the participant has either completed the study, withdrawn or ceased the study due to any other reason. I have reviewed the data in the case report form and found them to be complete and accurate.

Principal Investigator’s signature with date

CONFIDENTIAL

page 101 of 101