A Single-center, Double-blind, Randomized, Placebo-controlled Phase 1 Study to Investigate the Safety, Tolerability, and Pharmacokinetics of Single- and Multiple-ascending Doses of ACT-777991 in Healthy Subjects
Trial Snapshot
- Phase
- Phase 1
- Status
- Completed
- Sponsor
- Idorsia Pharmaceuticals Ltd.
- Enrollment
- 70
- Locations
- 1
- Primary Endpoint
- Incidence of treatment-emergent adverse events.
Study Overview
Brief Summary
A study to examine the safety, tolerability, and pharmacokinetics of single- and multiple-ascending doses of ACT-777991 in healthy subjects.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Sequential
- Primary Purpose
- Other
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- 18 Years to 55 Years (Adult)
- Sex
- All
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- •Signed informed consent in a language understandable to the subject prior to any study-mandated procedure.
- •Healthy male (Part A and B) and female subjects (Part B) aged between 18 and 55 years (inclusive) at Screening.
- •Healthy on the basis of medical history, physical examination, cardiovascular assessments, and clinical laboratory tests.
- •Male subjects with a partner who might become pregnant must either be vasectomized or agree to practice adequate contraception from admission to the study site until 3 months after dosing, or the partner must consistently and correctly use a highly effective method of contraception.
- •Inclusion Criteria for Part B:
- •Women of childbearing potential must have a negative serum pregnancy test at Screening and a negative urine pregnancy test on Day -
- •They must consistently and correctly use a highly effective method of contraception with a failure rate of less than 1% per year, be sexually inactive, or have a vasectomized partner.
- •Women of non-childbearing potential must have a negative serum pregnancy test at Screening and a negative urine pregnancy test on Day -
Exclusion Criteria
- •Any circumstances or conditions, which, in the opinion of the investigator, may affect full participation in the study or compliance with the protocol.
- •History or clinical evidence of any disease and/or existence of any surgical or medical condition, which, in the opinion of the investigator, are likely to interfere with the absorption, distribution, metabolism, or excretion of the study treatment.
- •Exclusion Criteria for the absorption,distribution, metabolism and excretion (ADME) evaluation:
- •Radiation exposure, excluding background radiation but including diagnostic X-rays and other medical exposures, exceeding 5 milli sievert (mSv) in the last 12 months or 10 mSv in the last 5 years. Occupationally exposed workers, as defined in the relevant Ionising Radiation Regulations, must not participate in the study.
- •Participation in any study involving administration of any Carbon-14 (14C) radiolabeled compound within the 12 months prior to Screening.
- •Exclusion Criteria for Part B:
- •Pregnant or lactating women.
Arms & Interventions
Part B (multiple ascending dose) Dose B4
Multiple doses B4 of ACT-777991.
Intervention: Placebo (MAD) (Drug)
Part B (multiple ascending dose) Dose B5
Multiple doses B5 of ACT-777991.
Intervention: ACT-777991 (MAD) (Drug)
Part B (multiple ascending dose) Dose B5
Multiple doses B5 of ACT-777991.
Intervention: Placebo (MAD) (Drug)
Part A (single ascending dose arm) Dose A5
Single dose A5 of ACT-777991.
Intervention: Placebo (SAD) (Drug)
Part B (multiple ascending dose) Dose B3
Multiple doses B3 of ACT-777991.
Intervention: Placebo (MAD) (Drug)
Part A (single ascending dose) Dose A1
Single dose A1 of ACT-777991.
Intervention: ACT-777991 (SAD) (Drug)
Part A (single ascending dose) Dose A1
Single dose A1 of ACT-777991.
Intervention: Placebo (SAD) (Drug)
Part A (single ascending dose arm) Dose A2
Single dose A2 of ACT-777991.
Intervention: ACT-777991 (SAD) (Drug)
Part A (single ascending dose arm) Dose A2
Single dose A2 of ACT-777991.
Intervention: Placebo (SAD) (Drug)
Part A (single ascending dose arm) Dose A3
Single dose A3 of ACT-777991.
Intervention: ACT-777991 (SAD) (Drug)
Part A (single ascending dose arm) Dose A3
Single dose A3 of ACT-777991.
Intervention: Placebo (SAD) (Drug)
Part A (single ascending dose arm) Dose A4
Single dose A4 of ACT-777991 under fasted and fed conditions, separated by at least 14 days.
Intervention: ACT-777991 (SAD) (Drug)
Part A (single ascending dose arm) Dose A4
Single dose A4 of ACT-777991 under fasted and fed conditions, separated by at least 14 days.
Intervention: Placebo (SAD) (Drug)
Part A (single ascending dose arm) Dose A5
Single dose A5 of ACT-777991.
Intervention: ACT-777991 (SAD) (Drug)
Part A (single ascending dose arm) Dose A6
Single dose A6 of ACT-777991.
Intervention: ACT-777991 (SAD) (Drug)
Part A (single ascending dose arm) Dose A6
Single dose A6 of ACT-777991.
Intervention: Placebo (SAD) (Drug)
Part A (single ascending dose arm) Dose A7
Single dose A7 of ACT-777991.
Intervention: ACT-777991 (SAD) (Drug)
Part A (single ascending dose arm) Dose A7
Single dose A7 of ACT-777991.
Intervention: Placebo (SAD) (Drug)
Part A (single ascending dose arm) Dose A8
Single dose A8 of ACT-777991.
Intervention: ACT-777991 (SAD) (Drug)
Part B (multiple ascending dose) Dose B4
Multiple doses B4 of ACT-777991.
Intervention: ACT-777991 (MAD) (Drug)
Part A (single ascending dose arm) Dose A8
Single dose A8 of ACT-777991.
Intervention: Placebo (SAD) (Drug)
Part B (multiple ascending dose) Dose B1
Multiple doses B1 of ACT-777991.
Intervention: ACT-777991 (MAD) (Drug)
Part B (multiple ascending dose) Dose B1
Multiple doses B1 of ACT-777991.
Intervention: Placebo (MAD) (Drug)
Part B (multiple ascending dose) Dose B2
Multiple doses B2 of ACT-777991.
Intervention: ACT-777991 (MAD) (Drug)
Part B (multiple ascending dose) Dose B2
Multiple doses B2 of ACT-777991.
Intervention: Placebo (MAD) (Drug)
Part B (multiple ascending dose) Dose B3
Multiple doses B3 of ACT-777991.
Intervention: ACT-777991 (MAD) (Drug)
Part A (single ascending dose) Absolute Bioavailability
Single dose of ACT-777991 plus a single dose of 14C-ACT-777991. At one of the dose levels from A4 to A8.
Intervention: 14C-ACT-777991 microtracer (SAD - Absolute Bioavailability) (Drug)
Part A (single ascending dose) Absolute Bioavailability
Single dose of ACT-777991 plus a single dose of 14C-ACT-777991. At one of the dose levels from A4 to A8.
Intervention: Microtracer matching placebo (SAD - Absolute Bioavailability) (Drug)
Part B (multiple ascending dose) ADME
Multiple doses of ACT-777991 plus a single dose of 14C-ACT-777991. At one of the dose levels from B1 to B5.
Intervention: 14C-ACT-777991 microtracer (MAD - ADME) (Drug)
Part B (multiple ascending dose) ADME
Multiple doses of ACT-777991 plus a single dose of 14C-ACT-777991. At one of the dose levels from B1 to B5.
Intervention: Microtracer matching placebo (MAD - ADME) (Drug)
Outcomes
Primary Outcomes
Incidence of treatment-emergent adverse events.
Time Frame: From first dose on Day 1 to Day 4 after the last dose was administered
Secondary Outcomes
- All cohorts: Area under the plasma concentration-time curve (AUC) from zero to infinity (AUC0-inf) of ACT-777991(Blood samples will be collected at predefined time points from Day 1 to Day 4 after the last dose was administered)
- Part A (SAD): Absolute bioavailability of ACT-777991(Blood samples will be collected at predefined time points from Day 1 to Day 4 after the last dose was administered)
- Part A (SAD): Food effect evaluation only: t1/2 of ACT 777991 under fed conditions(Blood samples will be collected at predefined time points from Day 1 to Day 4.)
- All cohorts: Time to reach Cmax (tmax) of ACT-777991(Blood samples will be collected at predefined time points from Day 1 to Day 4 after the last dose was administered)
- Part B (MAD): AUC during a dosing interval (AUCτ) following the first and the last dose of ACT-777991.(Blood samples will be collected at predefined time points from Day 1 to Day 4 after the last dose was administered)
- Part A (SAD): Food effect evaluation only: Cmax of ACT-777991 under fed conditions(Blood samples will be collected at predefined time points from Day 1 to Day 4.)
- All cohorts: Terminal half-life (t1/2) of ACT-777991(Blood samples will be collected at predefined time points from Day 1 to Day 4 after the last dose was administered)
- Part A (SAD): Food effect evaluation only: AUC0-inf of ACT-777991 under fed conditions(Blood samples will be collected at predefined time points from Day 1 to Day 4.)
- Part A (SAD): Food effect evaluation only: tmax of ACT-777991 under fed conditions(Blood samples will be collected at predefined time points from Day 1 to Day 4.)
- All cohorts: Area under the plasma concentration-time curve (AUC) from zero to time t of the last measured concentration above the limit of quantification (AUC0-t) of ACT-777991(Blood samples will be collected at predefined time points from Day 1 to Day 4 after the last dose was administered)
- Part B (MAD): Excretion of radioactivity in urine and feces(Samples will be collected at predefined time points from Day 1 to Day X+3 (where Day X = day of last study treatment administration))
- All cohorts: Maximum plasma concentration (Cmax) of ACT-777991(Blood samples will be collected at predefined time points from Day 1 to Day 4 after the last dose was administered)