A Single Ascending Dose Study of ACT-541468 in Healthy Male Subjects
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
2 other identifiers
interventional
40
1 country
1
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_1
Started Feb 2015
Shorter than P25 for phase_1
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
February 1, 2015
CompletedPrimary Completion
Last participant's last visit for primary outcome
May 1, 2015
CompletedStudy Completion
Last participant's last visit for all outcomes
May 1, 2015
CompletedFirst Submitted
Initial submission to the registry
September 28, 2016
CompletedFirst Posted
Study publicly available on registry
September 29, 2016
CompletedJuly 10, 2018
July 1, 2018
3 months
September 28, 2016
July 6, 2018
Conditions
Outcome Measures
Primary Outcomes (1)
Number of subjects with treatment-emergent adverse events and serious adverse events
Collection of any adverse event at each dose level
Day 8
Secondary Outcomes (6)
Maximum plasma concentration (Cmax) of ACT-541468
From pre-dose up to 168 hours post-dose
Time to reach Cmax (tmax) of ACT-541468
From pre-dose up to 168 hours post-dose
Terminal half-life (t1/2) of ACT-541468
From pre-dose up to 168 hours post-dose
Area under the plasma concentration-time curves [AUC(0-inf)] of ACT-541468
From pre-dose up to 168 hours post-dose
Percentage of dose excreted in feces and urine
From pre-dose up to 168 hours post-dose
- +1 more secondary outcomes
Other Outcomes (4)
Change from baseline in saccadic peak velocity (SPV)
At baseline till 10 hours after study drug administration
Change from baseline in body sway
At baseline till 10 hours after study drug administration
Change from baseline in adaptive tracking
At baseline till 10 hours after study drug administration
- +1 more other outcomes
Study Arms (5)
Dose group 1
EXPERIMENTALSix subjects received 5 mg of ACT-541468 (formulation A) as a single oral dose and two subjects received the matching placebo.
Dose group 2
EXPERIMENTALThree 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.
Dose group 3
EXPERIMENTALSix 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.
Dose group 4
EXPERIMENTALSix 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.
Dose group 5
EXPERIMENTALSix subjects received 200 mg of ACT-541468 (formulation A) as a single oral dose and two subjects received the matching placebo.
Interventions
Hard gelatin capsules for oral administration formulated at strengths of 5 mg, 25 mg and 100 mg
Soft gelatin capsules for oral administration formulated at the strength of 25 mg
Hard capsules matching ACT-541468 Formulation A
Tracer at a nominal dose of 250 nCi (corresponding to 2.02 µg ACT-541468) administered either orally or intravenously
Sterile NaCl 0.9% was used as placebo matching the tracer for oral and i.v. administration.
Eligibility Criteria
You may qualify if:
- 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.
You may not qualify if:
- 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
Investigator Site
Leiden, 2333 CL, Netherlands
MeSH Terms
Interventions
Study Officials
- STUDY DIRECTOR
Clemens Muehlan
Actelion
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- RANDOMIZED
- Masking
- TRIPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR
- Purpose
- OTHER
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
September 28, 2016
First Posted
September 29, 2016
Study Start
February 1, 2015
Primary Completion
May 1, 2015
Study Completion
May 1, 2015
Last Updated
July 10, 2018
Record last verified: 2018-07