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Completed

NCT Number: NCT02919319

A Single Ascending Dose Study of ACT-541468 in Healthy Male Subjects

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.

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Key information

Conditions

Healthy Subjects

Age range

18 year–45 year

Sex eligibility

Male

Study type

Interventional

Phase

Phase 1

Primary location

Investigator Site

Leiden, 2333 CL, Netherlands

About this study

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).

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

ACT-541468 (Formulation A)

Drug

Hard gelatin capsules for oral administration formulated at strengths of 5 mg, 25 mg and 100 mg

ACT-541468 (Formulation B)

Drug

Soft gelatin capsules for oral administration formulated at the strength of 25 mg

Placebo (Formulation A)

Drug

Hard capsules matching ACT-541468 Formulation A

Placebo (Formulation B)

Drug

Soft capsules matching ACT-541468 Formulation B

14C-labeled ACT-541468

Drug

Tracer at a nominal dose of 250 nCi (corresponding to 2.02 µg ACT-541468) administered either orally or intravenously

Placebo tracer

Drug

Sterile NaCl 0.9% was used as placebo matching the tracer for oral and i.v. administration.

Primary outcomes

  1. Number of subjects with treatment-emergent adverse events and serious adverse events

    Time frame: Day 8

    Collection of any adverse event at each dose level

Secondary outcomes

  1. Maximum plasma concentration (Cmax) of ACT-541468

    Time frame: From pre-dose up to 168 hours post-dose

    Cmax was directly derived from the observed plasma concentrations of ACT-541468 for each dose level

  2. Time to reach Cmax (tmax) of ACT-541468

    Time frame: From pre-dose up to 168 hours post-dose

    tmax was directly derived from the observed plasma concentrations of ACT-541468 for each dose level

  3. Terminal half-life (t1/2) of ACT-541468

    Time frame: From pre-dose up to 168 hours post-dose

    t1/2 was calculated from the terminal rate constant obtained from the plasma concentrations-time curves of ACT-541468, at each dose level

  4. Area under the plasma concentration-time curves [AUC(0-inf)] of ACT-541468

    Time frame: From pre-dose up to 168 hours post-dose

    AUC(0-inf) is the area under the plasma concentration-time curves of ACT-541468, calculated from time 0 (pre-dose) to extrapolated infinite time, at each dose level

  5. Percentage of dose excreted in feces and urine

    Time frame: From pre-dose up to 168 hours post-dose

    Percentage of oral dose of 14C-labeled ACT-541468 excreted in feces (FPE), urine (UPE) and both, as determined in the dose group 3

  6. Absolute bioavailability (F) of ACT-541468

    Time frame: Up to 96 hours post-dose

    Absolute bioavailability was determined for dose group 4 and defined as the ratio of AUC(0-inf) after oral administration of ACT-541468 and after intravenous infusion of 14C-labeled ACT-541468 (tracer)

Other outcomes

  1. Change from baseline in saccadic peak velocity (SPV)

    Time frame: At baseline till 10 hours after study drug administration

  2. Change from baseline in body sway

    Time frame: At baseline till 10 hours after study drug administration

  3. Change from baseline in adaptive tracking

    Time frame: At baseline till 10 hours after study drug administration

  4. Chnage from baseline in Bond and Lader visual analog scale (B&L VAS)l

    Time frame: At baseline till 10 hours after study drug administration

Sponsors and collaborators

Lead sponsor

Idorsia Pharmaceuticals Ltd.

Industry

Registry information

Official study 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

Important dates

Study start
2015
Primary completion
2015
Study completion
2015
First posted
Sep 29, 2016
Registry last updated
Jul 10, 2018

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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