A Study to Examine the Safety, Tolerability, and Pharmacokinetics of Single- and Multiple-ascending Doses of ACT-1014-6470 in Healthy Subjects

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-1014-6470 in Healthy Subjects, Including Food Effect, Mass Balance, and Metabolite Profiling

A study to examine the safety, tolerability, and pharmacokinetics of single- and multiple-ascending doses of ACT-1014-6470 in healthy subjects

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: ACT-1014-6470 (SAD); Drug: Placebo (SAD); Drug: 14C-ACT-1014-6470 microtracer; Drug: 14C-ACT-1014-6470 microtracer placebo; Drug: ACT-1014-6470 (MAD); Drug: Placebo (MAD)

• Study Type: Interventional
• Enrollment (Actual): 88
• Phase: Phase 1

Contacts and Locations

Study Locations

• Netherlands
  • Groningen, Netherlands, 9728 NZ
    • PRA Health Sciences

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (ADULT)
• Accepts Healthy Volunteers: Yes
• 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 < 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 ADME evaluation (Part A) only:

• Radiation exposure, excluding background radiation but including diagnostic X-rays and other medical exposures, exceeding 5 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 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
• Masking: QUADRUPLE

Number of Arms

10

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Part A (SAD): Dose A1; Single dose A1 of ACT-1014-6470; soft capsule for oral use.	Drug: ACT-1014-6470 (SAD); Single dose of ACT-1014-6470; soft capsules for oral use.; Drug: Placebo (SAD); Single dose of matching placebo; soft capsules for oral use.
EXPERIMENTAL: Part A (SAD): Dose A2; Single dose A2 of ACT-1014-6470; soft capsule for oral use.	Drug: ACT-1014-6470 (SAD); Single dose of ACT-1014-6470; soft capsules for oral use.; Drug: Placebo (SAD); Single dose of matching placebo; soft capsules for oral use.
EXPERIMENTAL: Part A (SAD): Dose A3; Single dose A3 of ACT-1014-6470 under fasted and fed conditions, separated by at least 18 days; soft capsule for oral use.	Drug: ACT-1014-6470 (SAD); Single dose of ACT-1014-6470; soft capsules for oral use.; Drug: Placebo (SAD); Single dose of matching placebo; soft capsules for oral use.
EXPERIMENTAL: Part A (SAD): Dose A4; Single dose A4 of ACT-1014-6470; soft capsule for oral use.	Drug: ACT-1014-6470 (SAD); Single dose of ACT-1014-6470; soft capsules for oral use.; Drug: Placebo (SAD); Single dose of matching placebo; soft capsules for oral use.; Drug: 14C-ACT-1014-6470 microtracer; Single dose of 14C-ACT-1014-6470 microtracer; soft capsules for oral use.; Drug: 14C-ACT-1014-6470 microtracer placebo; Single dose of matching placebo; soft capsules for oral use.
EXPERIMENTAL: Part A (SAD): Dose A5; Single dose A5 of ACT-1014-6470; soft capsule for oral use.	Drug: ACT-1014-6470 (SAD); Single dose of ACT-1014-6470; soft capsules for oral use.; Drug: Placebo (SAD); Single dose of matching placebo; soft capsules for oral use.
EXPERIMENTAL: Part A (SAD): Dose A6; Single dose A6 of ACT-1014-6470; soft capsule for oral use.	Drug: ACT-1014-6470 (SAD); Single dose of ACT-1014-6470; soft capsules for oral use.; Drug: Placebo (SAD); Single dose of matching placebo; soft capsules for oral use.
EXPERIMENTAL: Part B (MAD): Dose B1; Multiple doses B1 of ACT-1014-6470; soft capsules for oral use.	Drug: ACT-1014-6470 (MAD); Multiple doses of ACT-1014-6470; soft capsules for oral use.; Drug: Placebo (MAD); Multiple doses of matching placebo; soft capsules for oral use.
EXPERIMENTAL: Part B (MAD): Dose B2; Multiple doses B2 of ACT-1014-6470; soft capsules for oral use.	Drug: ACT-1014-6470 (MAD); Multiple doses of ACT-1014-6470; soft capsules for oral use.; Drug: Placebo (MAD); Multiple doses of matching placebo; soft capsules for oral use.
EXPERIMENTAL: Part B (MAD): Dose B3; Multiple doses B3 of ACT-1014-6470; soft capsules for oral use.	Drug: ACT-1014-6470 (MAD); Multiple doses of ACT-1014-6470; soft capsules for oral use.; Drug: Placebo (MAD); Multiple doses of matching placebo; soft capsules for oral use.
EXPERIMENTAL: Part B (MAD): Dose B4; Multiple doses B4 of ACT-1014-6470; soft capsules for oral use.	Drug: ACT-1014-6470 (MAD); Multiple doses of ACT-1014-6470; soft capsules for oral use.; Drug: Placebo (MAD); Multiple doses of matching placebo; soft capsules for oral use.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
All cohorts: Area under the plasma concentration-time curve (AUC) from zero to infinity (AUC0-inf)	Blood samples for determination of PK parameters will be collected at predefined time points from Day 1 to Day 4 of Part A (SAD, Day 1 to Day 8 for ADME cohort A4) and from Day 1 to Day X+3 of Part B (MAD, with Day X = day of last study treatment administration).	Total duration of assessments: up to 3 weeks.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
All cohorts: Maximum plasma concentration (Cmax).	Blood samples for determination of PK parameters will be collected at predefined time points from Day 1 to Day 4 of Part A (SAD, Day 1 to Day 8 for ADME cohort A4) and from Day 1 to Day X+3 of Part B (MAD, with Day X = day of last study treatment administration)	Total duration of assessments: up to 3 weeks.
All cohorts: Time to reach Cmax (tmax).	Blood samples for determination of PK parameters will be collected at predefined time points from Day 1 to Day 4 of Part A (SAD, Day 1 to Day 8 for ADME cohort A4) and from Day 1 to Day X+3 of Part B (MAD, with Day X = day of last study treatment administration)	Total duration of assessments: up to 3 weeks.
All cohorts: t½.	Blood samples for determination of PK parameters will be collected at predefined time points from Day 1 to Day 4 of Part A (SAD, Day 1 to Day 8 for ADME cohort A4) and from Day 1 to Day X+3 of Part B (MAD, with Day X = day of last study treatment administration)	Total duration of assessments: up to 3 weeks.
Food effect evaluation only: AUC0-inf under fasted conditions.	Blood samples for determination of PK parameters will be collected at predefined time points from Day 1 to Day 4 of Part A (SAD)	Total duration of assessments: up to 3 weeks.
Food effect evaluation only: Cmax under fasted conditions.	Blood samples for determination of PK parameters will be collected at predefined time points from Day 1 to Day 4 of Part A (SAD)	Total duration of assessments: up to 3 weeks.
Food effect evaluation only: tmax under fasted conditions.	Blood samples for determination of PK parameters will be collected at predefined time points from Day 1 to Day 4 of Part A (SAD)	Total duration of assessments: up to 3 weeks.
Food effect evaluation only: t½ under fasted conditions	Blood samples for determination of PK parameters will be collected at predefined time points from Day 1 to Day 4 of Part A (SAD)	Total duration of assessments: up to 3 weeks.
Part B (MAD): AUC during a dosing interval (AUCτ) following the first and the last dose.	Blood samples for determination of PK parameters will be collected at predefined time points from Day 1 to Day X+3 of Part B (MAD, with Day X = day of last study treatment administration)	Total duration of assessments: up to 3 weeks.
Treatment-emergent adverse events (AEs)	From start of study treatment administration up to End-of-Study (EOS) or End-of-Period (EOP). - Treatment-emergent serious AEs from the start of the study treatment administration up to EOS or EOP.	Total duration of assessments: up to 3 weeks.
Treatment-emergent serious adverse events (SAEs)	From start of study treatment administration up to End-of-Study (EOS) or End-of-Period (EOP). - Treatment-emergent serious AEs from the start of the study treatment administration up to EOS or EOP.	Total duration of assessments: up to 3 weeks.

Collaborators and Investigators

• Sponsor: Idorsia Pharmaceuticals Ltd.

Study record dates

Study Major Dates

• Study Start (ACTUAL): November 25, 2019
• Primary Completion (ACTUAL): March 15, 2020
• Study Completion (ACTUAL): March 15, 2020

Study Registration Dates

• First Submitted: November 26, 2019
• First Submitted That Met QC Criteria: November 28, 2019
• First Posted (ACTUAL): December 3, 2019

Study Record Updates

• Last Update Posted (ACTUAL): August 12, 2020
• Last Update Submitted That Met QC Criteria: August 11, 2020
• Last Verified: August 1, 2020

More Information

Terms related to this study

• Other Study ID Numbers: ID-087-101

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