Clinical trial NCT02919319: A Single Ascending Dose Study of ACT-541468 in Healthy Male Subjects
Official title: Double-blind, Placebo-controlled, Randomized, Single Ascending Dose Study to Investigate the Tolerability, Safety, Pharmacokinetics, Pharmacodynamics, Absolute Bioavailability, Mass Balance, and Metabolism of ACT-541468 in Healthy Male Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Subjects
Lead sponsor: Idorsia Pharmaceuticals Ltd.
Sponsor class: INDUSTRY
First posted: 2016-09-29
Enrollment: 40
Sex: MALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

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).

Eligibility 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.

Primary outcomes:
measure: Number of subjects with treatment-emergent adverse events and serious adverse events
timeFrame: Day 8
Secondary outcomes:
measure: Maximum plasma concentration (Cmax) of ACT-541468
timeFrame: From pre-dose up to 168 hours post-dose
measure: Time to reach Cmax (tmax) of ACT-541468
timeFrame: From pre-dose up to 168 hours post-dose
measure: Terminal half-life (t1/2) of ACT-541468
timeFrame: From pre-dose up to 168 hours post-dose
measure: Area under the plasma concentration-time curves [AUC(0-inf)] of ACT-541468
timeFrame: From pre-dose up to 168 hours post-dose
measure: Percentage of dose excreted in feces and urine
timeFrame: From pre-dose up to 168 hours post-dose
measure: Absolute bioavailability (F) of ACT-541468
timeFrame: Up to 96 hours post-dose
Other outcomes:
measure: Change from baseline in saccadic peak velocity (SPV)
timeFrame: At baseline till 10 hours after study drug administration
measure: Change from baseline in body sway
timeFrame: At baseline till 10 hours after study drug administration
measure: Change from baseline in adaptive tracking
timeFrame: At baseline till 10 hours after study drug administration
measure: Chnage from baseline in Bond and Lader visual analog scale (B&L VAS)l
timeFrame: At baseline till 10 hours after study drug administration
Locations:
city: Leiden
country: Netherlands
facility: Investigator Site
Study officials:
affiliation: Actelion
name: Clemens Muehlan
role: STUDY_DIRECTOR
References: