A Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Single Ascending Doses of ACT-1004-1239 in Healthy Male Subjects

Study Overview
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Brief Summary
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This Phase 1 study will assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of single ascending doses of ACT-1004-1239 in healthy subjects.

Official Title
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A Single-center, Phase 1 Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Single Ascending Doses of ACT-1004-1239 in Healthy Male Subjects (Including Food Interaction, Absolute Bioavailability, Mass Balance, and Metabolite Profiling)

Conditions
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Healthy

Intervention / Treatment
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* Drug: ACT-1004-1239
* Other: Placebo
* Drug: ACT-1004-1239 (Food-effect subpart)
* Other: Placebo (Food-effect subpart)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed informed consent in a language understandable to the subject prior to any study-mandated procedure. Healthy male subjects aged between 18 and 55 years (inclusive) at Screening. No sperm donation from (first) study treatment administration up to at least 90 days after (last) study treatment administration. Sexual abstinence or use of condoms from (first) treatment administration up to at least 90 days after (last) study treatment administration. Moreover, the female partner of childbearing potential must use a highly effective method of contraception. 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. Any previous and/or ongoing relevant immune-related disorder or any evidence for immune dysfunction based on medical history and laboratory tests at Screening Any cardiac condition or illness (including clinically relevant 12-lead ECG abnormalities) with a potential to increase the cardiac risk of the subject based on medical history and 12-lead ECG measured at Screening. QT interval corrected with Fridericia's formula (QTcF) > 430 ms, respectively, QRS interval > 110 ms, PR interval > 200 ms, or heart rate (HR) > 90 bpm on 12-lead ECG at Screening and Day 1 pre-dose (of the first period when applicable). Treatment with another investigational treatment within the 2 months prior to Screening or participation in more than 3 investigational treatment studies within the year prior to Screening. History or clinical evidence of any disease and/or existence of any surgical or medical condition that might interfere with the ADME of the study treatment (e.g., appendectomy and herniotomy allowed, cholecystectomy not allowed). Previous treatment with any prescribed medications (including vaccines and strong CYP3A4 inhibitors/inducers) or over-the-counter (OTC) medications (including homeopathic preparations, herbal medicines, vitamins, and minerals) within the 2 weeks or 5 terminal half-lives (t½; whichever is longer) prior to (first) study treatment administration.

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: Parallel Assignment
Interventional Model Description: Single-center, double-blind, randomized, placebo-controlled, single-ascending dose, Phase 1 study. The food effect will be assessed using a two-period, fixed-sequence design.
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ACT-1004-1239<br>ACT-1004-1239 will be given as a single oral dose under fasting conditions. Eight doses are planned with a starting dose of 1 mg. The ADME characteristics and absolute bioavailability using a 14C-radiolabeled microtracer will be evaluated as part of the SAD, after the first 3 cohorts have been performed. | Drug: ACT-1004-1239<br>* ACT-1004-1239 will be available for clinical study use as hard gelatin capsules for oral administration formulated in strengths of 1, 10, and 100 mg. For the ADME subpart, a single oral dose of 1 μCi of 14C radiolabeled ACT-1004-1239 will be given simultaneously with the ACT-1004-1239 capsule. For the absolute bioavailability subpart, a single intravenous dose of a maximum of 1 μCi of 14C radiolabeled ACT-1004-1239 will be given at the expected tmax after the administration of the ACT-1004-1239 capsule.<br>|
| Placebo Comparator: Placebo<br>Matching placebo will be given as a single oral dose under fasted conditions. Matching placebo for the oral and intravenous administration of the 14C-radiolabeled ACT-1004-1239 will also be available. | Other: Placebo<br>* Matching placebo is available as matching capsules for oral administration, formulated with the same excipients but without ACT-1004-1239.<br>|
| Experimental: Food-effect subpart: ACT-1004-1239<br>ACT-1004-1239 will be given under both fasted (first period) and fed (second period) conditions. The food effect will be evaluated after the first 3 cohorts have been performed. | Drug: ACT-1004-1239 (Food-effect subpart)<br>* ACT-1004-1239 will be available for clinical study use as hard gelatin capsules for oral administration formulated in strengths of 1, 10, and 100 mg.<br>|
| Placebo Comparator: Food-effect subpart: Placebo<br>Matching placebo will be given under both fasted (first period) and fed (second period) conditions. | Other: Placebo (Food-effect subpart)<br>* Matching placebo is available as matching capsules for oral administration, formulated with the same excipients but without ACT-1004-1239.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patients with treatment-emergent (serious) adverse events (AEs and SAEs) |  | From baseline up to EOS of each cohort (total duration: up to 6 weeks) |