Clinical trial NCT04798209: A Study to Examine the Safety, Tolerability, and Pharmacokinetics of Single- and Multiple-ascending Doses of ACT-777991 in Healthy Subjects
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Lead sponsor: Idorsia Pharmaceuticals Ltd.
Sponsor class: INDUSTRY
First posted: 2021-03-15
Enrollment: 70
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: Single-center, double-blind, randomized, placebo-controlled Phase 1 study
Primary purpose: OTHER

Brief summary: A study to examine the safety, tolerability, and pharmacokinetics of single- and multiple-ascending doses of ACT-777991 in healthy subjects.


Eligibility 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.

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.

Primary outcomes:
measure: Incidence of treatment-emergent adverse events.
timeFrame: From first dose on Day 1 to Day 4 after the last dose was administered
Secondary outcomes:
measure: 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
timeFrame: Blood samples will be collected at predefined time points from Day 1 to Day 4 after the last dose was administered
measure: All cohorts: Area under the plasma concentration-time curve (AUC) from zero to infinity (AUC0-inf) of ACT-777991
timeFrame: Blood samples will be collected at predefined time points from Day 1 to Day 4 after the last dose was administered
measure: All cohorts: Maximum plasma concentration (Cmax) of ACT-777991
timeFrame: Blood samples will be collected at predefined time points from Day 1 to Day 4 after the last dose was administered
measure: All cohorts: Time to reach Cmax (tmax) of ACT-777991
timeFrame: Blood samples will be collected at predefined time points from Day 1 to Day 4 after the last dose was administered
measure: All cohorts: Terminal half-life (t1/2) of ACT-777991
timeFrame: Blood samples will be collected at predefined time points from Day 1 to Day 4 after the last dose was administered
measure: Part A (SAD): Absolute bioavailability of ACT-777991
timeFrame: Blood samples will be collected at predefined time points from Day 1 to Day 4 after the last dose was administered
measure: Part B (MAD): Excretion of radioactivity in urine and feces
timeFrame: Samples will be collected at predefined time points from Day 1 to Day X+3 (where Day X = day of last study treatment administration)
measure: Part B (MAD): AUC during a dosing interval (AUCτ) following the first and the last dose of ACT-777991.
timeFrame: Blood samples will be collected at predefined time points from Day 1 to Day 4 after the last dose was administered
measure: Part A (SAD): Food effect evaluation only: AUC0-inf of ACT-777991 under fed conditions
timeFrame: Blood samples will be collected at predefined time points from Day 1 to Day 4.
measure: Part A (SAD): Food effect evaluation only: Cmax of ACT-777991 under fed conditions
timeFrame: Blood samples will be collected at predefined time points from Day 1 to Day 4.
measure: Part A (SAD): Food effect evaluation only: tmax of ACT-777991 under fed conditions
timeFrame: Blood samples will be collected at predefined time points from Day 1 to Day 4.
measure: Part A (SAD): Food effect evaluation only: t1/2 of ACT 777991 under fed conditions
timeFrame: Blood samples will be collected at predefined time points from Day 1 to Day 4.
Other outcomes:
Locations:
city: Groningen
country: Netherlands
facility: QPS Netherlands B.V.
Study officials:
affiliation: Idorsia Pharmaceuticals Ltd.
name: Clinical Trials
role: STUDY_DIRECTOR
References: