A Study to Examine the Safety, Tolerability, and Pharmacokinetics of Single- and Multiple-ascending Doses of ACT-777991 in Healthy Subjects
Phase 1
Completed
- Conditions
- Healthy
- Interventions
- Drug: ACT-777991 (SAD)Drug: ACT-777991 (MAD)Drug: 14C-ACT-777991 microtracer (MAD - ADME)Drug: 14C-ACT-777991 microtracer (SAD - Absolute Bioavailability)Drug: Placebo (SAD)Drug: Placebo (MAD)Drug: Microtracer matching placebo (SAD - Absolute Bioavailability)Drug: Microtracer matching placebo (MAD - ADME)
- Registration Number
- NCT04798209
- Lead Sponsor
- Idorsia Pharmaceuticals Ltd.
- Brief Summary
A study to examine the safety, tolerability, and pharmacokinetics of single- and multiple-ascending doses of ACT-777991 in healthy subjects.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 70
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 -1. 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 -1.
General
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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Part A (single ascending dose arm) Dose A4 Placebo (SAD) Single dose A4 of ACT-777991 under fasted and fed conditions, separated by at least 14 days. Part A (single ascending dose) Dose A1 ACT-777991 (SAD) Single dose A1 of ACT-777991. Part A (single ascending dose arm) Dose A7 Placebo (SAD) Single dose A7 of ACT-777991. Part A (single ascending dose arm) Dose A2 Placebo (SAD) Single dose A2 of ACT-777991. Part A (single ascending dose arm) Dose A3 ACT-777991 (SAD) Single dose A3 of ACT-777991. Part A (single ascending dose arm) Dose A6 ACT-777991 (SAD) Single dose A6 of ACT-777991. Part A (single ascending dose arm) Dose A7 ACT-777991 (SAD) Single dose A7 of ACT-777991. Part B (multiple ascending dose) Dose B4 Placebo (MAD) Multiple doses B4 of ACT-777991. Part A (single ascending dose arm) Dose A4 ACT-777991 (SAD) Single dose A4 of ACT-777991 under fasted and fed conditions, separated by at least 14 days. Part A (single ascending dose arm) Dose A5 ACT-777991 (SAD) Single dose A5 of ACT-777991. Part B (multiple ascending dose) Dose B2 ACT-777991 (MAD) Multiple doses B2 of ACT-777991. Part B (multiple ascending dose) Dose B3 ACT-777991 (MAD) Multiple doses B3 of ACT-777991. Part A (single ascending dose) Absolute Bioavailability Microtracer matching placebo (SAD - 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. Part A (single ascending dose) Dose A1 Placebo (SAD) Single dose A1 of ACT-777991. Part A (single ascending dose arm) Dose A2 ACT-777991 (SAD) Single dose A2 of ACT-777991. Part A (single ascending dose arm) Dose A3 Placebo (SAD) Single dose A3 of ACT-777991. Part A (single ascending dose arm) Dose A6 Placebo (SAD) Single dose A6 of ACT-777991. Part A (single ascending dose arm) Dose A8 ACT-777991 (SAD) Single dose A8 of ACT-777991. Part A (single ascending dose arm) Dose A8 Placebo (SAD) Single dose A8 of ACT-777991. Part B (multiple ascending dose) Dose B2 Placebo (MAD) Multiple doses B2 of ACT-777991. Part B (multiple ascending dose) Dose B3 Placebo (MAD) Multiple doses B3 of ACT-777991. Part B (multiple ascending dose) Dose B4 ACT-777991 (MAD) Multiple doses B4 of ACT-777991. Part B (multiple ascending dose) Dose B5 Placebo (MAD) Multiple doses B5 of ACT-777991. Part B (multiple ascending dose) ADME 14C-ACT-777991 microtracer (MAD - ADME) Multiple doses of ACT-777991 plus a single dose of 14C-ACT-777991. At one of the dose levels from B1 to B5. Part A (single ascending dose arm) Dose A5 Placebo (SAD) Single dose A5 of ACT-777991. Part B (multiple ascending dose) Dose B1 ACT-777991 (MAD) Multiple doses B1 of ACT-777991. Part B (multiple ascending dose) Dose B1 Placebo (MAD) Multiple doses B1 of ACT-777991. Part B (multiple ascending dose) Dose B5 ACT-777991 (MAD) Multiple doses B5 of ACT-777991. Part A (single ascending dose) Absolute Bioavailability 14C-ACT-777991 microtracer (SAD - 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. Part B (multiple ascending dose) ADME Microtracer matching placebo (MAD - ADME) Multiple doses of ACT-777991 plus a single dose of 14C-ACT-777991. At one of the dose levels from B1 to B5.
- Primary Outcome Measures
Name Time Method Incidence of treatment-emergent adverse events. From first dose on Day 1 to Day 4 after the last dose was administered
- Secondary Outcome Measures
Name Time Method 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 (AUCĪ) 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 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 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 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. 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.
Trial Locations
- Locations (1)
QPS Netherlands B.V.
đŗđąGroningen, Netherlands