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

Idorsia Pharmaceuticals

Status and phase: Completed; Phase 1

Conditions: Pharmacodynamics; Tolerability; Pharmacokinetics; Safety

Treatments: Drug: ACT-462206 1500mg; Drug: ACT-462206 5 mg; Drug: Almorexant 400mg; Drug: ACT-462206 400mg; Drug: ACT-462206 200mg; Drug: ACT-462206 25 mg; Drug: Placebo; Drug: ACT-462206 1000 mg; Drug: ACT-462206 100mg

Study type: Interventional

Funder types: Industry

Identifiers

NCT01954589

AC-074-101

Details and patient eligibility

About

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.

Full 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).

Enrollment: 56 patients

Sex: Male

Ages: 18 to 45 years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Other

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Triple Blind

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56 participants in 7 patient groups

ACT-462206 5 mg/Placebo

Experimental group

Description:

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

Treatment:

Drug: Placebo

Drug: ACT-462206 5 mg

ACT-462206 25 mg/Placebo

Experimental group

Description:

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

Treatment:

Drug: Placebo

Drug: ACT-462206 25 mg

ACT-462206 100mg/Placebo

Experimental group

Description:

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

Treatment:

Drug: Placebo

Drug: ACT-462206 100mg

ACT-462206 200mg/Almorexant 400mg/Placebo

Experimental group

Description:

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

Treatment:

Drug: Placebo

Drug: ACT-462206 200mg

Drug: Almorexant 400mg

Experimental: ACT-462206 400mg/Placebo

Experimental group

Description:

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

Treatment:

Drug: Placebo

Drug: ACT-462206 400mg

ACT-462206 1000 mg

Experimental group

Description:

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

Treatment:

Drug: Placebo

Drug: ACT-462206 1000 mg

ACT-462206 1500mg/Placebo

Experimental group

Description:

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

Treatment:

Drug: Placebo

Drug: ACT-462206 1500mg