A Single Ascending Dose Study of ACT-541468 in Healthy Male Subjects

NCT ID: NCT02919319

Last Updated: 2018-07-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-02-01
• Study Completion Date: 2015-05-01

Brief Summary

The main objectives of this first-into-man study were to investigate the safety, tolerability and the pharmacokinetic profile of single oral doses of ACT-541468 in healthy male adults. Pharmacodynamic effects (through a battery of Central Nervous System tests) were also assessed.

Detailed Description

The study consisted of ascending dose groups; each dose group was investigated in a new group of 8 healthy male subjects (6 on active drug and 2 on placebo). In addition, the study included a biocomparison part (dose group 2), an absolute bioavailability part (dose group 4), and a mass balance / metabolism part (dose group 3).

Conditions

Healthy Subjects

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: OTHER
• Blinding Strategy: TRIPLE

Study Groups

Dose group 1

Six subjects received 5 mg of ACT-541468 (formulation A) as a single oral dose and two subjects received the matching placebo.

Group Type: EXPERIMENTAL

ACT-541468 (Formulation A)

Intervention Type: DRUG

Hard gelatin capsules for oral administration formulated at strengths of 5 mg, 25 mg and 100 mg

Placebo (Formulation A)

Intervention Type: DRUG

Hard capsules matching ACT-541468 Formulation A

Dose group 2

Three subjects received a single oral dose (25 mg) of ACT-541468 formulation A during Period 1 and a single oral dose (25 mg) of ACT-541468 formulation B during Period 2. Three other subjects Subjects received ACT-541468 formulation B during Period 1 and ACT-541468 formulation A during Period 2. Two additional subjects received the matching placebos in both treatment periods.

Group Type: EXPERIMENTAL

ACT-541468 (Formulation A)

Intervention Type: DRUG

Hard gelatin capsules for oral administration formulated at strengths of 5 mg, 25 mg and 100 mg

ACT-541468 (Formulation B)

Intervention Type: DRUG

Soft gelatin capsules for oral administration formulated at the strength of 25 mg

Placebo (Formulation A)

Intervention Type: DRUG

Hard capsules matching ACT-541468 Formulation A

Placebo (Formulation B)

Intervention Type: DRUG

Soft capsules matching ACT-541468 Formulation B

Dose group 3

Six subjects received 50 mg of ACT-541468 (formulation A) as a single oral dose in combination with a \[14C\]-ACT-541468 oral tracer for the mass balance and metabolism analyses. Two other subjects received the matching placebos.

Group Type: EXPERIMENTAL

ACT-541468 (Formulation A)

Intervention Type: DRUG

Hard gelatin capsules for oral administration formulated at strengths of 5 mg, 25 mg and 100 mg

Placebo (Formulation A)

Intervention Type: DRUG

Hard capsules matching ACT-541468 Formulation A

14C-labeled ACT-541468

Intervention Type: DRUG

Tracer at a nominal dose of 250 nCi (corresponding to 2.02 µg ACT-541468) administered either orally or intravenously

Placebo tracer

Intervention Type: DRUG

Sterile NaCl 0.9% was used as placebo matching the tracer for oral and i.v. administration.

Dose group 4

Six subjects received 100 mg of ACT-541468 (formulation A) as a single oral dose in combination with a \[14C\]-ACT-541468 intravenous tracer for the absolute bioavailability assessment. Two other subjects received the matching placebos.

Group Type: EXPERIMENTAL

ACT-541468 (Formulation A)

Intervention Type: DRUG

Hard gelatin capsules for oral administration formulated at strengths of 5 mg, 25 mg and 100 mg

Placebo (Formulation A)

Intervention Type: DRUG

Hard capsules matching ACT-541468 Formulation A

14C-labeled ACT-541468

Intervention Type: DRUG

Tracer at a nominal dose of 250 nCi (corresponding to 2.02 µg ACT-541468) administered either orally or intravenously

Placebo tracer

Intervention Type: DRUG

Sterile NaCl 0.9% was used as placebo matching the tracer for oral and i.v. administration.

Dose group 5

Six subjects received 200 mg of ACT-541468 (formulation A) as a single oral dose and two subjects received the matching placebo.

Group Type: EXPERIMENTAL

ACT-541468 (Formulation A)

Intervention Type: DRUG

Hard gelatin capsules for oral administration formulated at strengths of 5 mg, 25 mg and 100 mg

Placebo (Formulation A)

Intervention Type: DRUG

Hard capsules matching ACT-541468 Formulation A

Interventions

ACT-541468 (Formulation A)

Hard gelatin capsules for oral administration formulated at strengths of 5 mg, 25 mg and 100 mg

Intervention Type: DRUG

ACT-541468 (Formulation B)

Soft gelatin capsules for oral administration formulated at the strength of 25 mg

Intervention Type: DRUG

Placebo (Formulation A)

Hard capsules matching ACT-541468 Formulation A

Intervention Type: DRUG

Placebo (Formulation B)

Soft capsules matching ACT-541468 Formulation B

Intervention Type: DRUG

14C-labeled ACT-541468

Tracer at a nominal dose of 250 nCi (corresponding to 2.02 µg ACT-541468) administered either orally or intravenously

Intervention Type: DRUG

Placebo tracer

Sterile NaCl 0.9% was used as placebo matching the tracer for oral and i.v. administration.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Signed informed consent prior to any study-mandated procedure.
• Males aged from 18 to 45 years (inclusive) at screening.
• Body mass index (BMI) between 18.0 and 30.0 kg/m2 (inclusive) at screening.
• Systolic blood pressure (SBP), diastolic blood pressure (DBP) and pulse rate (PR) between 100-145 mmHg, 50-90 mmHg and 45-90 bpm (all inclusive) at screening, respectively.
• Healthy on the basis of physical examination,electrocardiogram and laboratory tests.

Exclusion Criteria

• Known hypersensitivity to any excipients of the drug formulations.
• History or presence of any disease or condition or treatment, which may put the subject at risk of participation in the study or may interfere with the absorption, distribution, metabolism or excretion of the study drugs.
• History of narcolepsy or cataplexy or modified Swiss narcolepsy scale total score < 0 at screening.
• Any circumstances or conditions, which, in the opinion of the investigator, may affect the subject's full participation in the study or compliance with the protocol.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 45 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: Yes

Sponsors

Idorsia Pharmaceuticals Ltd.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clemens Muehlan

Role: STUDY_DIRECTOR

Actelion

Locations

Investigator Site

Leiden, , Netherlands

Countries

Netherlands

Other Identifiers

2014-003129-16

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

AC-078-101

Identifier Type: -

Identifier Source: org_study_id