Clinical Trial Simulation to Inform Phase 2

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ustekinumab. -2.4. 2.63. -0.1 discontinumab. -0.288. 2.47. -0.1. No-Go. Examples mehmimab. -0.598. 3.47. -0.1 cuspmimab. -1.05. 3.47. -0.1 lowpomab. -2.4.
Clinical Trial Simulation to Inform Phase 2: Comparison of Concentrated Versus Distributed First-in-Patient Study Designs in Psoriasis

M. G. Dodds,1 D. H. Salinger,1 J. Mandema,2 J. P. Gibbs,1 M.A. Gibbs1* 1Department of Pharmacokinetics & Drug Metabolism, Amgen, Inc., Seattle, WA; 2Quantitative Solutions, Menlo Park, CA

Table S-1 Test Case Potency Parameters and Desired Trial Outcome Simulation Parameters in log domain Group Marketed Examples No-Go Examples Go Examples

Compound

Emax

ED50

E0

adalimumab

-2.4

2.834

-0.1

golimumab

-2.4

3.82

-0.1

ustekinumab

-2.4

2.63

-0.1

discontinumab

-0.288

2.47

-0.1

mehmimab

-0.598

3.47

-0.1

cuspmimab

-1.05

3.47

-0.1

lowpomab

-2.4

5.20

-0.1

nopomab

-2.4

6.59

-0.1

Phase 1 FIP CTS

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Model Control file. Eight designs (DESNO) were considered, and the control file did not vary between designs and was produced using a script. The data file contains the dose (DOSE), design (DSN) and drug (DRUG) logic as columns to control the simulation and back-estimation process. ;Model Desc: PsO simulator, using mean change in PASI; DATE; Design DESNO ;Project Name: p1 trial design ;Project ID: NO PROJECT DESCRIPTION $PROB RUN# RUNNO $INPUT C ID DOSE DSN DRUG TE0 TEMAX TED50 TEDRUG DV $DATA ../SimData_DATE_DESNO.csv IGNORE=C $PRED ; control stream set to handle a single design for multiple drugs ; as the design information really resides in the data file ; load the typical population values, depending on which drug we're talking about IF( DRUG.EQ.1 ) THEN E0=THETA(1) EMAX=THETA(2) ED50=THETA(3) ENDIF IF( DRUG.EQ.2 ) THEN E0=THETA(4) EMAX=THETA(5) ED50=THETA(6) ENDIF IF( DRUG.EQ.3 ) THEN E0=THETA(7) EMAX=THETA(8) ED50=THETA(9) ENDIF IF( DRUG.EQ.4 ) THEN E0=THETA(10) EMAX=THETA(11) ED50=THETA(12) ENDIF IF( DRUG.EQ.5 ) THEN E0=THETA(13) EMAX=THETA(14) ED50=THETA(15) ENDIF IF( DRUG.EQ.6 ) THEN

Phase 1 FIP CTS

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E0=THETA(16) EMAX=THETA(17) ED50=THETA(18) ENDIF IF( DRUG.EQ.7 ) THEN E0=THETA(19) EMAX=THETA(20) ED50=THETA(21) ENDIF IF( DRUG.EQ.8 ) THEN E0=THETA(22) EMAX=THETA(23) ED50=THETA(24) ENDIF SERR = THETA(25) IERR = THETA(26) E0=E0+ETA(1) ; $OMEGA[1,1] is set to zero, so this does not play a role in the simulation or estimation ; step (see "$OMEGA" below) ; BEGIN ESTIMATION MODEL DEFINITIONS ; prediction for % change in PASI ; DSN