Clinical trial NCT01954589: Single-ascending Dose Study to Investigate the Tolerability, Safety, Pharmacokinetics, and Pharmacodynamics of ACT-462206
Official title: Double-blind, Placebo- and Active-controlled, Randomized, Single-ascending Dose Study to Investigate the Tolerability, Safety, Pharmacokinetics, and Pharmacodynamics of ACT-462206 in Healthy Male Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Safety
Tolerability
Pharmacodynamics
Pharmacokinetics
Keywords: ACT-462206
Selective dual orexin receptor antagonist
Lead sponsor: Idorsia Pharmaceuticals Ltd.
Sponsor class: INDUSTRY
First posted: 2013-10-07
Enrollment: 56
Sex: MALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: OTHER

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).

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

Primary outcomes:
measure: Change in supine systolic blood pressure from baseline up to the end of study
timeFrame: 96 hours
measure: Change in supine diastolic blood pressure from baseline up to the end of study
timeFrame: 96 hours
measure: Change in heart rate from baseline up to the end of study
timeFrame: 96 hours
measure: Change in body weight from baseline up to the end of study
timeFrame: 96 hours
measure: Change in PR Interval from baseline up to the end of study
timeFrame: 96 hours
measure: Change in QRS Interval from baseline up to the end of study
timeFrame: 96 hours
measure: Change in QTcB Interval from baseline up to the end of study
timeFrame: 96 hours
measure: Change in QTcF Interval from baseline up to the end of study
timeFrame: 96 hours
measure: Change in saccadic peak velocity from baseline up to the end of study
timeFrame: 10 hours
measure: Change in performance on adaptive tracking from baseline up to the end of study
timeFrame: 10 hours
measure: Change in body sway from baseline up to the end of study
timeFrame: 10 hours
measure: Change in visual analogue scale (VAS) score to assess alertness from baseline up to the end of study
timeFrame: 10 hours
measure: Change in VAS score to assess mood from baseline up to the end of study
timeFrame: 10 hours
measure: Change in VAS score to assess calmness from baseline up to the end of study
timeFrame: 10 hours
Secondary outcomes:
measure: Maximum plasma concentration (Cmax) of ACT-462206
timeFrame: 96 hours
measure: Time to reach maximum plasma concentration (tmax) of ACT-462206
timeFrame: 96 hours
measure: Area under the plasma concentration-time curve (AUC) from time zero to time t of the last measured concentration above the limit of quantification (AUC0-t) of ACT-462206
timeFrame: 96 hours
measure: AUC from time zero to infinity (AUC0-∞) of ACT-462206
timeFrame: 96 hours
measure: AUC from time zero to 8 hours after administration (AUC0-8) of ACT-462206
timeFrame: 8 hours
measure: AUC from time zero to 24 hours after administration (AUC0-24) of ACT-462206
timeFrame: 24 hours
Other outcomes:
Locations:
city: Leiden
country: Netherlands
facility: Centre for Human Drug Research
Study officials:
affiliation: Actelion
name: Petra Baecker, MD
role: STUDY_DIRECTOR
References: