A Study to Examine the Safety, Tolerability, and Pharmacokinetics of Single- and Multiple-ascending Doses of ACT-777991 in Healthy Subjects

Healthy Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04798209
• Other study ID #: ID-089-101
• Secondary ID: 2020-004464-26
• Status: Completed
• Phase: Phase 1
• Start date: January 29, 2021
• Est. completion date: May 21, 2022

Study information

• Verified date: June 2022
• Source: Idorsia Pharmaceuticals Ltd.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 70
• Est. completion date: May 21, 2022
• Est. primary completion date: January 26, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

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.

Related Conditions & MeSH terms

• Healthy

Intervention

Drug:
• ACT-777991 (SAD)
ACT-777991 administered as hard capsules for oral use.
• ACT-777991 (MAD)
ACT-777991 administered as hard capsules for oral use, once daily.
• Placebo (SAD)
ACT-777991 matching placebo administered as hard capsules for oral use.
• Placebo (MAD)
Matching placebo administered as hard capsules for oral use, once daily.
• 14C-ACT-777991 microtracer (SAD - Absolute Bioavailability)
Single dose of 14C-ACT-777991 microtracer, administered intravenously.
• Microtracer matching placebo (SAD - Absolute Bioavailability)
Single dose of 14C-ACT-777991 microtracer matching placebo, administered intravenously.
• 14C-ACT-777991 microtracer (MAD - ADME)
Single dose of 14C-ACT-777991 microtracer, oral solution..
• Microtracer matching placebo (MAD - ADME)
Single dose of 14C-ACT-777991 microtracer matching placebo, oral solution.

Locations

Country	Name	City	State
Netherlands	QPS Netherlands B.V.	Groningen

Sponsors (1)

Lead Sponsor	Collaborator
Idorsia Pharmaceuticals Ltd.

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of treatment-emergent adverse events.		From first dose on Day 1 to Day 4 after the last dose was administered
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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)
Secondary	Part B (MAD): AUC during a dosing interval (AUCt) 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
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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.