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

Idorsia Pharmaceuticals

Status and phase: Completed; Phase 1

Conditions: Healthy Subjects

Treatments: Drug: Placebo (Formulation B); Drug: Placebo tracer; Drug: ACT-541468 (Formulation B); Drug: ACT-541468 (Formulation A); Drug: Placebo (Formulation A); Drug: 14C-labeled ACT-541468

Study type: Interventional

Funder types: Industry

Identifiers

NCT02919319

AC-078-101

2014-003129-16 (EudraCT Number)

Details and patient eligibility

About

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.

Full 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).

Enrollment: 40 patients

Sex: Male

Ages: 18 to 45 years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion criteria

Key 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.

Key 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.

Trial design

Primary purpose: Other

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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40 participants in 5 patient groups

Dose group 1

Experimental group

Description:

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

Treatment:

Drug: ACT-541468 (Formulation A)

Drug: Placebo (Formulation A)

Dose group 2

Experimental group

Description:

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.

Treatment:

Drug: ACT-541468 (Formulation B)

Drug: ACT-541468 (Formulation A)

Drug: Placebo (Formulation B)

Drug: Placebo (Formulation A)

Dose group 3

Experimental group

Description:

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.

Treatment:

Drug: Placebo tracer

Drug: ACT-541468 (Formulation A)

Drug: 14C-labeled ACT-541468

Drug: Placebo (Formulation A)

Dose group 4

Experimental group

Description:

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.

Treatment:

Drug: Placebo tracer

Drug: ACT-541468 (Formulation A)

Drug: 14C-labeled ACT-541468

Drug: Placebo (Formulation A)

Dose group 5

Experimental group

Description:

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

Treatment:

Drug: ACT-541468 (Formulation A)

Drug: Placebo (Formulation A)