Single-ascending Dose Study to Investigate the Tolerability, Safety, Pharmacokinetics, and Pharmacodynamics of ACT-462206

NCT ID: NCT01954589

Last Updated: 2018-07-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 56 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-11-30
• Study Completion Date: 2012-01-31

Brief Summary

A study of ACT-462206 to evaluate the tolerability, safety, pharmacokinetics, and pharmacodynamic of ascending single doses of ACT-462206, a novel dual orexin receptor antagonist in healthy male subjects.

Detailed Description

Each dose level will be investigated in a new group of eight healthy male subjects (six on active drug and two on placebo). Each subject will participate in one treatment period, with the exception of subjects in the crossover part (i.e., almorexant reference group at the fourth dose level), who will participate in two treatment periods. At this dose level subjects on active drug (six) will receive in one treatment period ACT-462206 and in the other 400 mg of almorexant; subjects on placebo (two) will receive the corresponding placebos (double-dummy).

Conditions

Safety; Tolerability; Pharmacodynamics; Pharmacokinetics

Study Design

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

Study Groups

ACT-462206 5 mg/Placebo

6 subjects received a single, 5 mg, oral dose of ACT-462206 and 2 subjects received a single, oral dose of placebo

Group Type: EXPERIMENTAL

ACT-462206 5 mg

Intervention Type: DRUG

Placebo

Intervention Type: DRUG

ACT-462206 25 mg/Placebo

6 subjects received a single, 25 mg, oral dose of ACT-462206 and 2 subjects received a single, oral dose of placebo

Group Type: EXPERIMENTAL

ACT-462206 25 mg

Intervention Type: DRUG

Placebo

Intervention Type: DRUG

ACT-462206 100mg/Placebo

6 subjects received a single, 100 mg, oral dose of ACT-462206 and 2 subjects received a single, oral dose of placebo

Group Type: EXPERIMENTAL

ACT-462206 100mg

Intervention Type: DRUG

Placebo

Intervention Type: DRUG

ACT-462206 200mg/Almorexant 400mg/Placebo

Subjects were assigned to one of two possible treatment sequences: A/B or B/A with a washout period of 14 days between treatment periods.

Treatment A: Single oral dose of ACT-462206 200 mg or placebo. Treatment B: Single oral dose of almorexant 400 mg or placebo. In each sequence 6 subjects received ACT-462206 or almorexant & 2 subjects received placebo

Group Type: EXPERIMENTAL

ACT-462206 200mg

Intervention Type: DRUG

Almorexant 400mg

Intervention Type: DRUG

Placebo

Intervention Type: DRUG

Experimental: ACT-462206 400mg/Placebo

6 subjects received a single, 400 mg, oral dose of ACT-462206 and 2 subjects received a single, oral dose of placebo

Group Type: EXPERIMENTAL

ACT-462206 400mg

Intervention Type: DRUG

Placebo

Intervention Type: DRUG

ACT-462206 1000 mg

6 subjects received a single, 1000 mg, oral dose of ACT-462206 and 2 subjects received a single, oral dose of placebo

Group Type: EXPERIMENTAL

ACT-462206 1000 mg

Intervention Type: DRUG

Placebo

Intervention Type: DRUG

ACT-462206 1500mg/Placebo

6 subjects received a single, 1500 mg, oral dose of ACT-462206 and 2 subjects received a single, oral dose of placebo

Group Type: EXPERIMENTAL

ACT-462206 1500mg

Intervention Type: DRUG

Placebo

Intervention Type: DRUG

Interventions

ACT-462206 5 mg

Intervention Type: DRUG

ACT-462206 25 mg

Intervention Type: DRUG

ACT-462206 100mg

Intervention Type: DRUG

ACT-462206 200mg

Intervention Type: DRUG

ACT-462206 400mg

Intervention Type: DRUG

ACT-462206 1000 mg

Intervention Type: DRUG

ACT-462206 1500mg

Intervention Type: DRUG

Almorexant 400mg

Intervention Type: DRUG

Placebo

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Healthy male subjects aged between 18 and 45 years (inclusive) at screening
• Hematology, clinical chemistry, and urinalysis results not deviating from the normal range to a clinically relevant extent at screening
• No clinically significant findings on physical examination at screening
• Body mass index between 18.0 and 28.0 kg/m^2 (inclusive) at screening
• Systolic blood pressure 100-145 mmHg, diastolic blood pressure 50-90 mmHg, and heart rate 45-90 beats per minute (inclusive) measured at screening on the dominant arm (dominant arm is the writing arm) after 5 min in supine position
• 12-lead electrocardiogram without clinically relevant abnormalities in the supine position at screening
• Negative results from urine drug screen at screening
• Ability to communicate well with the investigator in the local language, and to understand and comply with the requirements of the study.

Exclusion Criteria

• Previous history of fainting, collapse, syncope, orthostatic hypotension, or vasovagal reactions
• Veins unsuitable for intravenous puncture on either arm (e.g., veins that are difficult to locate, access or puncture, veins with a tendency to rupture during or after puncture)
• Treatment with any prescribed medications (including vaccines) or over-the-counter medications (including herbal medicines such as St John's Wort) within 2 weeks prior to (first) study drug administration
• Treatment with another investigational drug within 3 months prior to screening or having participated in more than four investigational drug studies within 1 year prior to screening
• History or clinical evidence of alcoholism or drug abuse within the 3-year period prior to screening
• History or clinical evidence of any disease, and/or existence of any surgical or medical condition, which might interfere with the absorption, distribution, metabolism or excretion of the study drugs
• Excessive caffeine consumption, defined as ≥ 800 mg per day at screening of caffeine)
• Smoking within 3 months prior to screening and inability to refrain from smoking during the course of the study
• Loss of 250 mL or more of blood, or an equivalent amount of plasma, within 3 months prior to screening
• Positive results from the hepatitis serology, except for vaccinated subjects or subjects with past but resolved hepatitis, at screening
• Positive results from the human immunodeficiency virus serology at screening
• Known hypersensitivity to any excipients of the drug formulations
• Modified Swiss Narcolepsy Scale total score < 0 or history of narcolepsy or cataplexy
• Any circumstances or conditions, which, in the opinion of the investigator, might affect full participation in the study or compliance with the protocol
• Legal incapacity or limited legal capacity at screening

• 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

Petra Baecker, MD

Role: STUDY_DIRECTOR

Actelion

Locations

Centre for Human Drug Research

Leiden, , Netherlands

Countries

Netherlands

Other Identifiers

AC-074-101

Identifier Type: -

Identifier Source: org_study_id