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

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

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

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: ACT-777991 (SAD); Drug: Placebo (SAD); Drug: ACT-777991 (MAD); Drug: Placebo (MAD); Drug: 14C-ACT-777991 microtracer (SAD - Absolute Bioavailability); Drug: Microtracer matching placebo (SAD - Absolute Bioavailability); Drug: 14C-ACT-777991 microtracer (MAD - ADME); Drug: Microtracer matching placebo (MAD - ADME)

• Study Type: Interventional
• Enrollment (Actual): 70
• Phase: Phase 1

Contacts and Locations

Study Locations

• Netherlands
  • Groningen, Netherlands, 9713 GZ
    • QPS Netherlands B.V.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Quadruple

Number of Arms

15

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part A (single ascending dose) Dose A1; Single dose A1 of ACT-777991.	Drug: ACT-777991 (SAD); ACT-777991 administered as hard capsules for oral use.; Drug: Placebo (SAD); ACT-777991 matching placebo administered as hard capsules for oral use.
Experimental: Part A (single ascending dose arm) Dose A2; Single dose A2 of ACT-777991.	Drug: ACT-777991 (SAD); ACT-777991 administered as hard capsules for oral use.; Drug: Placebo (SAD); ACT-777991 matching placebo administered as hard capsules for oral use.
Experimental: Part A (single ascending dose arm) Dose A3; Single dose A3 of ACT-777991.	Drug: ACT-777991 (SAD); ACT-777991 administered as hard capsules for oral use.; Drug: Placebo (SAD); ACT-777991 matching placebo administered as hard capsules for oral use.
Experimental: 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.	Drug: ACT-777991 (SAD); ACT-777991 administered as hard capsules for oral use.; Drug: Placebo (SAD); ACT-777991 matching placebo administered as hard capsules for oral use.
Experimental: Part A (single ascending dose arm) Dose A5; Single dose A5 of ACT-777991.	Drug: ACT-777991 (SAD); ACT-777991 administered as hard capsules for oral use.; Drug: Placebo (SAD); ACT-777991 matching placebo administered as hard capsules for oral use.
Experimental: Part A (single ascending dose arm) Dose A6; Single dose A6 of ACT-777991.	Drug: ACT-777991 (SAD); ACT-777991 administered as hard capsules for oral use.; Drug: Placebo (SAD); ACT-777991 matching placebo administered as hard capsules for oral use.
Experimental: Part A (single ascending dose arm) Dose A7; Single dose A7 of ACT-777991.	Drug: ACT-777991 (SAD); ACT-777991 administered as hard capsules for oral use.; Drug: Placebo (SAD); ACT-777991 matching placebo administered as hard capsules for oral use.
Experimental: Part A (single ascending dose arm) Dose A8; Single dose A8 of ACT-777991.	Drug: ACT-777991 (SAD); ACT-777991 administered as hard capsules for oral use.; Drug: Placebo (SAD); ACT-777991 matching placebo administered as hard capsules for oral use.
Experimental: Part B (multiple ascending dose) Dose B1; Multiple doses B1 of ACT-777991.	Drug: ACT-777991 (MAD); ACT-777991 administered as hard capsules for oral use, once daily.; Drug: Placebo (MAD); Matching placebo administered as hard capsules for oral use, once daily.
Experimental: Part B (multiple ascending dose) Dose B2; Multiple doses B2 of ACT-777991.	Drug: ACT-777991 (MAD); ACT-777991 administered as hard capsules for oral use, once daily.; Drug: Placebo (MAD); Matching placebo administered as hard capsules for oral use, once daily.
Experimental: Part B (multiple ascending dose) Dose B3; Multiple doses B3 of ACT-777991.	Drug: ACT-777991 (MAD); ACT-777991 administered as hard capsules for oral use, once daily.; Drug: Placebo (MAD); Matching placebo administered as hard capsules for oral use, once daily.
Experimental: Part B (multiple ascending dose) Dose B4; Multiple doses B4 of ACT-777991.	Drug: ACT-777991 (MAD); ACT-777991 administered as hard capsules for oral use, once daily.; Drug: Placebo (MAD); Matching placebo administered as hard capsules for oral use, once daily.
Experimental: Part B (multiple ascending dose) Dose B5; Multiple doses B5 of ACT-777991.	Drug: ACT-777991 (MAD); ACT-777991 administered as hard capsules for oral use, once daily.; Drug: Placebo (MAD); Matching placebo administered as hard capsules for oral use, once daily.
Experimental: 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.	Drug: 14C-ACT-777991 microtracer (SAD - Absolute Bioavailability); Single dose of 14C-ACT-777991 microtracer, administered intravenously.; Drug: Microtracer matching placebo (SAD - Absolute Bioavailability); Single dose of 14C-ACT-777991 microtracer matching placebo, administered intravenously.
Experimental: 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.	Drug: 14C-ACT-777991 microtracer (MAD - ADME); Single dose of 14C-ACT-777991 microtracer, oral solution..; Drug: Microtracer matching placebo (MAD - ADME); Single dose of 14C-ACT-777991 microtracer matching placebo, oral solution.

What is the study measuring?

Primary Outcome Measures

Outcome 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 Outcome Measures

Outcome Measure	Time Frame
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
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
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)
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.

Collaborators and Investigators

• Sponsor: Idorsia Pharmaceuticals Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): January 29, 2021
• Primary Completion (Actual): January 26, 2022
• Study Completion (Actual): May 21, 2022

Study Registration Dates

• First Submitted: March 3, 2021
• First Submitted That Met QC Criteria: March 11, 2021
• First Posted (Actual): March 15, 2021

Study Record Updates

• Last Update Posted (Actual): June 21, 2022
• Last Update Submitted That Met QC Criteria: June 17, 2022
• Last Verified: June 1, 2022

More Information

Terms related to this study

• Other Study ID Numbers: ID-089-101; 2020-004464-26 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No