A Study to Assess the Tolerability, Safety, Pharmacodynamics, and Pharmacokinetics of Ascending Single Doses (Including Food Interaction) and Ascending Multiple Doses of ACT-453859, and Multiple Doses of Setipiprant (ACT-129968)
Condition: Healthy
Study type: Interventional
Phase: Phase 1

Summary: 
      This is a three-part study to assess the tolerability, safety, pharmacodynamics, and
      pharmacokinetics of ascending single doses (including food interaction) of ACT-453859 in
      healthy male subjects, of ascending multiple doses of ACT-453859 in healthy male and female
      subjects, and of multiple doses of setipiprant (ACT-129968) in healthy male and female
      subjects.
    

Detailed description: 
      Part A of this study is a single-center, randomized, double-blind, placebo-controlled,
      single-ascending dose (SAD) design in healthy male subjects. In each cohort, eight subjects
      will be randomized as follows:

        -  Six male subjects will receive a single oral dose of ACT-453859, under fasted
           conditions.

        -  Two male subjects will receive matching placebo, under fasted conditions.

      The doses of ACT-453859 were 1, 3, 10, 30, 100, 300, and 800 mg. Subjects in only one cohort
      (100 mg dose cohort) will come back for a second period of treatment under fed conditions.

      Part B is a single-center, randomized, double-blind, placebo-controlled multiple-ascending
      dose (MAD) design in healthy male and female of subjects.

      In each of 3 cohorts, eight subjects will be randomized to receive multiple doses of
      ACT-453859 or placebo once a day for 7 days as follows:

        -  Three male subjects will receive ACT-453859.

        -  Three female subjects will receive ACT-453859.

        -  One male subject will receive matching placebo.

        -  One female subject will receive matching placebo.

      The doses of ACT-453859 will be 10, 100, and 800 mg per day.

      Part C is a single-center and open-label design consisting of multiple oral doses of
      setipiprant given in a sequential design in healthy male and female subjects.

      Eight subjects will be randomized to receive multiple doses of setipiprant for 7 days (only a
      single dose on Day 7), in Treatment Period I (TPI) and Treatment Period II (TPII), as
      follows:

        -  Four male subjects will receive setipiprant 500 mg twice a day (b.i.d.) in TPI and 1000
           mg b.i.d. in TPII.

        -  Four female subjects will receive setipiprant 500 mg b.i.d. in TPI and 1000 mg b.i.d. in
           TPII.
    

Intervention name(s): ACT-453859 1 mg; ACT-453859 3 mg; ACT-453859 10 mg; ACT-453859 30mg; ACT-453859 100 mg; ACT-453859 300 mg; ACT-453859 800 mg; Placebo; Setipiprant 500 mg; Setipiprant 1000 mg
Intervention type(s): Drug; Drug; Drug; Drug; Drug; Drug; Drug; Other; Drug; Drug
Intervention description(s): Capsule; Capsule; Capsule; Capsule; Capsule; Capsule; Capsule; Matching ACT-453859 placebo capsule; Capsule; Capsule
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary purpose: Other
Keywords: ACT-453859; ACT-463036; Setipiprant; Tolerability; safety; pharmacodynamics; pharmacokinetics