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

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ClinicalTrials.gov Identifier: NCT02919319
Recruitment Status : Completed
First Posted : September 29, 2016
Last Update Posted : July 10, 2018
Sponsor:
Information provided by (Responsible Party):
Idorsia Pharmaceuticals Ltd.

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.

Condition or disease Intervention/treatment Phase
Healthy Subjects Drug: ACT-541468 (Formulation A) Drug: ACT-541468 (Formulation B) Drug: Placebo (Formulation A) Drug: Placebo (Formulation B) Drug: 14C-labeled ACT-541468 Drug: Placebo tracer Phase 1

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).

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 40 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Other
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
Actual Study Start Date : February 1, 2015
Actual Primary Completion Date : May 1, 2015
Actual Study Completion Date : May 1, 2015

Arm Intervention/treatment
Experimental: Dose group 1
Six subjects received 5 mg of ACT-541468 (formulation A) as a single oral dose and two subjects received the matching placebo.
Drug: ACT-541468 (Formulation A)
Hard gelatin capsules for oral administration formulated at strengths of 5 mg, 25 mg and 100 mg

Drug: Placebo (Formulation A)
Hard capsules matching ACT-541468 Formulation A

Experimental: Dose group 2
Three 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.
Drug: ACT-541468 (Formulation A)
Hard gelatin capsules for oral administration formulated at strengths of 5 mg, 25 mg and 100 mg

Drug: ACT-541468 (Formulation B)
Soft gelatin capsules for oral administration formulated at the strength of 25 mg

Drug: Placebo (Formulation A)
Hard capsules matching ACT-541468 Formulation A

Drug: Placebo (Formulation B)
Soft capsules matching ACT-541468 Formulation B

Experimental: Dose group 3
Six 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.
Drug: ACT-541468 (Formulation A)
Hard gelatin capsules for oral administration formulated at strengths of 5 mg, 25 mg and 100 mg

Drug: Placebo (Formulation A)
Hard capsules matching ACT-541468 Formulation A

Drug: 14C-labeled ACT-541468
Tracer at a nominal dose of 250 nCi (corresponding to 2.02 µg ACT-541468) administered either orally or intravenously

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

Experimental: Dose group 4
Six 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.
Drug: ACT-541468 (Formulation A)
Hard gelatin capsules for oral administration formulated at strengths of 5 mg, 25 mg and 100 mg

Drug: Placebo (Formulation A)
Hard capsules matching ACT-541468 Formulation A

Drug: 14C-labeled ACT-541468
Tracer at a nominal dose of 250 nCi (corresponding to 2.02 µg ACT-541468) administered either orally or intravenously

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

Experimental: Dose group 5
Six subjects received 200 mg of ACT-541468 (formulation A) as a single oral dose and two subjects received the matching placebo.
Drug: ACT-541468 (Formulation A)
Hard gelatin capsules for oral administration formulated at strengths of 5 mg, 25 mg and 100 mg

Drug: Placebo (Formulation A)
Hard capsules matching ACT-541468 Formulation A




Primary Outcome Measures :
  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 Outcome Measures :
  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 Outcome Measures:
  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 ]


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Ages Eligible for Study:   18 Years to 45 Years   (Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02919319


Locations
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Netherlands
Investigator Site
Leiden, Netherlands, 2333 CL
Sponsors and Collaborators
Idorsia Pharmaceuticals Ltd.
Investigators
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Study Director: Clemens Muehlan Actelion

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Responsible Party: Idorsia Pharmaceuticals Ltd.
ClinicalTrials.gov Identifier: NCT02919319     History of Changes
Other Study ID Numbers: AC-078-101
2014-003129-16 ( EudraCT Number )
First Posted: September 29, 2016    Key Record Dates
Last Update Posted: July 10, 2018
Last Verified: July 2018