A 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

Study Overview
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Brief Summary
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A safety and tolerability study in healthy subjects including examination of how the body takes up, distributes, and gets rid of ACT-1014-6470

Official Title
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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-1014-6470 in Healthy Subjects

Conditions
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Healthy

Intervention / Treatment
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* Drug: ACT-1014-6470
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: General criteria Signed informed consent prior to any study-mandated procedure. Healthy male subjects (both study parts) and female subjects of nonchildbearing potential (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 that 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 (from Screening, during the entire study, and for at least 3 months after last study treatment intake) a highly effective method of contraception. Criteria for Part B only: • Women of non-childbearing potential must have a negative serum pregnancy test at Screening and a negative urine pregnancy test on Day-1. Exclusion Criteria: Previous exposure to the study medication. 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. Relevant bacterial, viral, fungal, or protozoal infection that manifested within the last 6 weeks prior to Screening and/or ongoing relevant bacterial, viral, fungal, or protozoal infection, as judged by the investigator, and/or evidence of immune dysfunction based on laboratory tests at Screening. Any signs or symptoms of active, ongoing infection judged to be clinically relevant by the investigator (special attention should be given to clinical signs and symptoms consistent with COVID-19, e.g., fever, dry cough, dyspnea, sore throat, or fatigue).

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- and multiple-ascending dose
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ACT-1014-6470 single dose (dose level 1)<br>Soft capsule for oral administration | Drug: ACT-1014-6470<br>* Soft capsules for oral administration<br>|
| Placebo Comparator: Placebo single dose (dose level 1)<br>Soft capsule for oral administration | Drug: Placebo<br>* Soft capsules for oral administration<br>|
| Experimental: ACT-1014-6470 single dose (dose level 2)<br>Soft capsule for oral administration | Drug: ACT-1014-6470<br>* Soft capsules for oral administration<br>|
| Placebo Comparator: Placebo single dose (dose level 2)<br>Soft capsule for oral administration | Drug: Placebo<br>* Soft capsules for oral administration<br>|
| Experimental: ACT-1014-6470 multiple dose (dose level 1)<br>Soft capsule for oral administration | Drug: ACT-1014-6470<br>* Soft capsules for oral administration<br>|
| Placebo Comparator: Placebo multiple dose (dose level 1)<br>Soft capsule for oral administration | Drug: Placebo<br>* Soft capsules for oral administration<br>|
| Experimental: ACT-1014-6470 multiple dose (dose level 2)<br>Soft capsule for oral administration | Drug: ACT-1014-6470<br>* Soft capsules for oral administration<br>|
| Placebo Comparator: Placebo multiple dose (dose level 2)<br>Soft capsule for oral administration | Drug: Placebo<br>* Soft capsules for oral administration<br>|
| Experimental: ACT-1014-6470 multiple dose (dose level 3)<br>Soft capsule for oral administration | Drug: ACT-1014-6470<br>* Soft capsules for oral administration<br>|
| Placebo Comparator: Placebo multiple dose (dose level 3)<br>Soft capsule for oral administration | Drug: Placebo<br>* Soft capsules for oral administration<br>|
| Experimental: ACT-1014-6470 multiple dose (dose level 4)<br>Soft capsule for oral administration | Drug: ACT-1014-6470<br>* Soft capsules for oral administration<br>|
| Placebo Comparator: Placebo multiple dose (dose level 4)<br>Soft capsule for oral administration | Drug: Placebo<br>* Soft capsules for oral administration<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety profile including incidence of treatment-emergent adverse events. |  | Safety and tolerability assessments will be performed at predefined time points from Day 1 to Day 4 in Part A and Day 1 to Day 10 in Part B (total duration: max. 50 days). | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part A - Single ascending dose (SAD): 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). |  | Blood samples for the determination of the PK parameters will be collected at predefined time points from Day 1 to Day 4 (total duration: max. 4 days). | 
| Part A - Single ascending dose (SAD): Area under the plasma concentration-time curve (AUC) from zero to infinity (AUC0-inf). |  | Blood samples for the determination of the PK parameters will be collected at predefined time points from Day 1 to Day 4 (total duration: max. 4 days). | 
| Part A - Single ascending dose (SAD): Maximum plasma concentration (Cmax). |  | Blood samples for the determination of the PK parameters will be collected at predefined time points from Day 1 to Day 4 (total duration: max. 4 days). | 
| Part A - Single ascending dose (SAD): Time to reach Cmax (tmax). |  | Blood samples for the determination of the PK parameters will be collected at predefined time points from Day 1 to Day 4 (total duration: max. 4 days). | 
| Part A - Single ascending dose (SAD): Terminal half-life (t½). |  | Blood samples for the determination of the PK parameters will be collected at predefined time points from Day 1 to Day 4 (total duration: max. 4 days). | 
| Part B - Multiple ascending dose (MAD): AUC during a dosing interval (AUCτ) following the first and the last dose. |  | Blood samples for the determination of the PK parameters will be collected at predefined time points from Day 1 to Day 10 (total duration: max. 10 days). | 
| Part B - Multiple ascending dose (MAD): Cmax of the first and the last dosing interval. |  | Blood samples for the determination of the PK parameters will be collected at predefined time points from Day 1 to Day 10 (total duration: max. 10 days). | 
| Part B - Multiple ascending dose (MAD): tmax of the first and the last dosing interval. |  | Blood samples for the determination of the PK parameters will be collected at predefined time points from Day 1 to Day 10 (total duration: max. 10 days). | 
| Part B - Multiple ascending dose (MAD): t½ after last dose administration. |  | Blood samples for the determination of the PK parameters will be collected at predefined time points from Day 1 to Day 10 (total duration: max. 10 days). |