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

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

Official Title
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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

Conditions
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Healthy

Intervention / Treatment
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* Drug: ACT-1014-6470 (SAD)
* Drug: ACT-1014-6470 (MAD)
* Drug: Placebo (SAD)
* Drug: Placebo (MAD)
* Drug: 14C-ACT-1014-6470 microtracer
* Drug: 14C-ACT-1014-6470 microtracer placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: Single-center, double-blind, randomized, placebo-controlled Phase 1 study
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part A (SAD): Dose A1<br>Single dose A1 of ACT-1014-6470; soft capsule for oral use. | Drug: ACT-1014-6470 (SAD)<br>* Single dose of ACT-1014-6470; soft capsules for oral use.<br>Drug: Placebo (SAD)<br>* Single dose of matching placebo; soft capsules for oral use.<br>|
| Experimental: Part A (SAD): Dose A2<br>Single dose A2 of ACT-1014-6470; soft capsule for oral use. | Drug: ACT-1014-6470 (SAD)<br>* Single dose of ACT-1014-6470; soft capsules for oral use.<br>Drug: Placebo (SAD)<br>* Single dose of matching placebo; soft capsules for oral use.<br>|
| Experimental: Part A (SAD): Dose A3<br>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)<br>* Single dose of ACT-1014-6470; soft capsules for oral use.<br>Drug: Placebo (SAD)<br>* Single dose of matching placebo; soft capsules for oral use.<br>|
| Experimental: Part A (SAD): Dose A4<br>Single dose A4 of ACT-1014-6470; soft capsule for oral use. | Drug: ACT-1014-6470 (SAD)<br>* Single dose of ACT-1014-6470; soft capsules for oral use.<br>Drug: Placebo (SAD)<br>* Single dose of matching placebo; soft capsules for oral use.<br>Drug: 14C-ACT-1014-6470 microtracer<br>* Single dose of 14C-ACT-1014-6470 microtracer; soft capsules for oral use.<br>Drug: 14C-ACT-1014-6470 microtracer placebo<br>* Single dose of matching placebo; soft capsules for oral use.<br>|
| Experimental: Part A (SAD): Dose A5<br>Single dose A5 of ACT-1014-6470; soft capsule for oral use. | Drug: ACT-1014-6470 (SAD)<br>* Single dose of ACT-1014-6470; soft capsules for oral use.<br>Drug: Placebo (SAD)<br>* Single dose of matching placebo; soft capsules for oral use.<br>|
| Experimental: Part A (SAD): Dose A6<br>Single dose A6 of ACT-1014-6470; soft capsule for oral use. | Drug: ACT-1014-6470 (SAD)<br>* Single dose of ACT-1014-6470; soft capsules for oral use.<br>Drug: Placebo (SAD)<br>* Single dose of matching placebo; soft capsules for oral use.<br>|
| Experimental: Part B (MAD): Dose B1<br>Multiple doses B1 of ACT-1014-6470; soft capsules for oral use. | Drug: ACT-1014-6470 (MAD)<br>* Multiple doses of ACT-1014-6470; soft capsules for oral use.<br>Drug: Placebo (MAD)<br>* Multiple doses of matching placebo; soft capsules for oral use.<br>|
| Experimental: Part B (MAD): Dose B2<br>Multiple doses B2 of ACT-1014-6470; soft capsules for oral use. | Drug: ACT-1014-6470 (MAD)<br>* Multiple doses of ACT-1014-6470; soft capsules for oral use.<br>Drug: Placebo (MAD)<br>* Multiple doses of matching placebo; soft capsules for oral use.<br>|
| Experimental: Part B (MAD): Dose B3<br>Multiple doses B3 of ACT-1014-6470; soft capsules for oral use. | Drug: ACT-1014-6470 (MAD)<br>* Multiple doses of ACT-1014-6470; soft capsules for oral use.<br>Drug: Placebo (MAD)<br>* Multiple doses of matching placebo; soft capsules for oral use.<br>|
| Experimental: Part B (MAD): Dose B4<br>Multiple doses B4 of ACT-1014-6470; soft capsules for oral use. | Drug: ACT-1014-6470 (MAD)<br>* Multiple doses of ACT-1014-6470; soft capsules for oral use.<br>Drug: Placebo (MAD)<br>* Multiple doses of matching placebo; soft capsules for oral use.<br>|

What is the study measuring?
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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. |