Phase 1 Study of ATR-002
Condition: Influenza
Study type: Interventional
Phase: Phase 1

Summary: 
      This was a combination of a single ascending dose (SAD) study to evaluate the safety,
      tolerability, and PK of 3 oral doses of a MEK inhibitor and a multiple ascending dose (MAD)
      study of 3 oral doses of a MEK inhibitor.

      Subjects were to be enrolled in 3 different cohorts in the SAD and 3 different cohorts in the
      MAD and were to be randomly (blinded) allocated to active treatment or placebo (each cohort
      consisted of 8 subjects receiving active treatment and 2 subjects receiving placebo).
    

Detailed description: 
      Each subject in the SAD cohorts was to receive a single dose of the MEK inhibitor ATR-002
      (PD0184264), with a starting dose of 100 mg ATR-002 or placebo:

        -  Cohort 1: 100 mg ATR-002 or placebo;

        -  Cohort 2: 100 mg + X mg ATR-002 or placebo;

        -  Cohort 3: 100 mg + X mg + Y mg ATR-002 or placebo. An additional cohort (Cohort 4) of 10
           subjects (4:1 active vs placebo) could have been recruited into the SAD Part, if
           appropriate.

      Effectively, 4 cohorts were treated:

        -  Cohort 1: 100 mg ATR-002 or placebo;

        -  Cohort 2: 300 mg ATR-002 or placebo;

        -  Cohort 3: 600 mg ATR-002 or placebo;

        -  Cohort 4: 900 mg ATR-002 or placebo. Between each cohort, a blinded interim analysis of
           PK, safety and tolerability had to be performed. The available data was evaluated by the
           Investigator and sponsor in a Safety Review Committee (SRC) meeting.

      Once a dose level was judged to be safe, the SRC determined the dose level for the next
      cohort considering a maximal increment of 400 mg compared to the previous cohort, and the
      next dose level could be administered to the next cohort.

      The maximal dose level could not exceed 900 mg ATR-002. Each subject in the MAD cohorts was
      to receive once daily (QD) doses (fasted) of the MEK inhibitor ATR-002 for 7 days, starting
      with a dose of 100 mg ATR-002 or placebo QD.

        -  Cohort 5: 100 mg ATR-002 QD or placebo;

        -  Cohort 6: 100 mg + A mg ATR-002 QD or placebo;

        -  Cohort 7: 100 mg + A mg + B mg ATR-002 QD or placebo. An additional cohort (Cohort 8) of
           10 subjects (4:1 active vs placebo) could be recruited into the MAD Part, if
           appropriate.

      Effectively, 3 cohorts were treated:

        -  Cohort 5: 100 mg ATR-002 QD or placebo;

        -  Cohort 6: 300 mg ATR-002 QD or placebo;

        -  Cohort 7: 600 mg ATR-002 QD or placebo. Between each cohort, a blinded interim analysis
           of PK, safety and tolerability had to be performed. The available data was evaluated by
           the Investigator and sponsor in a SRC meeting. Once a dose level was judged to be safe,
           the SCR determined the dose level for the next cohort considering a maximal increment of
           400 mg compared to the previous cohort, and the next dose level could be administered to
           the next cohort.

      The maximal dose level could not exceed 900 mg ATR-002. During the study, no repeated daily
      dose could exceed the maximum single dose that has been shown to cause no safety concerns.

      Subjects were resident on the ward from the day (late afternoon/evening) before dosing (Day
      -1) until completion of procedures at 96h following their final dose of study medication.
      They were to attend a follow up visit 28 days (± 2 days) following their final dose of study
      medication.

      Subjects with AEs that were ongoing at the end of the study were followed up as appropriate
      until the AEs had resolved or stabilised, up to a maximum of 30 days after the last dose of
      study drug.

      Pharmacokinetics were determined predose 30 min, 1h, 2h, 4h, 8h, 12h, and 24h, postdose, and
      predose on Day 2-4 in the SAD Part, and predose 30 min, 1h, 2h, 4h, 8h, 12h, and 24h, of Day
      1 and Day 7, predose on Day 2-6 and 48h, 72h, and 96h post final dose of Day 7 in the MAD
      Part. The 72h and 96h samples in both SAD and MAD were only to be analysed if deemed
      informative based on the results of the 48h PK sample.
    

Intervention name(s): ATR-002 MEK Inhibitor; Placebo oral tablet
Intervention type(s): Drug; Drug
Intervention description(s): Drug ATR-002 administered as film-coated tablet via oral route; Placebo film-coated tablet administered via oral route
Other intervention name(s): PD01842649
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: This was a combination of a single ascending dose (SAD) study to evaluate the safety, tolerability, and PK of 3 oral doses of a MEK inhibitor and a multiple ascending dose (MAD) study of 3 oral doses of a MEK inhibitor.
Subjects were to be enrolled in 3 different cohorts in the SAD and 3 different cohorts in the MAD and were to be randomly (blinded) allocated to active treatment or placebo (each cohort consisted of 8 subjects receiving active treatment and 2 subjects receiving placebo).
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment