Healthy
Conditions
Brief summary
A study to examine the safety, tolerability, and pharmacokinetics of single- and multiple-ascending doses of ACT-777991 in healthy subjects.
Interventions
DRUGACT-777991 (SAD)
ACT-777991 administered as hard capsules for oral use.
DRUGACT-777991 (MAD)
ACT-777991 administered as hard capsules for oral use, once daily.
DRUGPlacebo (SAD)
ACT-777991 matching placebo administered as hard capsules for oral use.
DRUGPlacebo (MAD)
Matching placebo administered as hard capsules for oral use, once daily.
DRUG14C-ACT-777991 microtracer (SAD - Absolute Bioavailability)
Single dose of 14C-ACT-777991 microtracer, administered intravenously.
DRUGMicrotracer matching placebo (SAD - Absolute Bioavailability)
Single dose of 14C-ACT-777991 microtracer matching placebo, administered intravenously.
DRUG14C-ACT-777991 microtracer (MAD - ADME)
Single dose of 14C-ACT-777991 microtracer, oral solution..
DRUGMicrotracer matching placebo (MAD - ADME)
Single dose of 14C-ACT-777991 microtracer matching placebo, oral solution.
Sponsors
Idorsia Pharmaceuticals Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
OTHER
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
Single-center, double-blind, randomized, placebo-controlled Phase 1 study
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
General 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Incidence of treatment-emergent adverse events. | From first dose on Day 1 to Day 4 after the last dose was administered |
Secondary
| Measure | Time frame |
|---|---|
| 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 |
| 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 |
| 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 |
| 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): 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 |
| 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): 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: 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: 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: tmax 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: t1/2 of ACT 777991 under fed conditions | Blood samples will be collected at predefined time points from Day 1 to Day 4. |
| 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) |
Countries
Netherlands
Outcome results
None listed