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

Healthy Subjects Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02919319
• Other study ID #: AC-078-101
• Secondary ID: 2014-003129-16
• Status: Completed
• Phase: Phase 1
• Start date: February 1, 2015
• Est. completion date: May 1, 2015

Study information

• Verified date: July 2018
• Source: Idorsia Pharmaceuticals Ltd.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 40
• Est. completion date: May 1, 2015
• Est. primary completion date: May 1, 2015
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 45 Years

Eligibility

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.

Related Conditions & MeSH terms

• Healthy Subjects

Intervention

Drug:
• ACT-541468 (Formulation A)
Hard gelatin capsules for oral administration formulated at strengths of 5 mg, 25 mg and 100 mg
• ACT-541468 (Formulation B)
Soft gelatin capsules for oral administration formulated at the strength of 25 mg
• Placebo (Formulation A)
Hard capsules matching ACT-541468 Formulation A
• Placebo (Formulation B)
Soft capsules matching ACT-541468 Formulation B
• 14C-labeled ACT-541468
Tracer at a nominal dose of 250 nCi (corresponding to 2.02 µg ACT-541468) administered either orally or intravenously
• Placebo tracer
Sterile NaCl 0.9% was used as placebo matching the tracer for oral and i.v. administration.

Locations

Country	Name	City	State
Netherlands	Investigator Site	Leiden

Sponsors (1)

Lead Sponsor	Collaborator
Idorsia Pharmaceuticals Ltd.

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Change from baseline in saccadic peak velocity (SPV)		At baseline till 10 hours after study drug administration
Other	Change from baseline in body sway		At baseline till 10 hours after study drug administration
Other	Change from baseline in adaptive tracking		At baseline till 10 hours after study drug administration
Other	Chnage from baseline in Bond and Lader visual analog scale (B&L VAS)l		At baseline till 10 hours after study drug administration
Primary	Number of subjects with treatment-emergent adverse events and serious adverse events	Collection of any adverse event at each dose level	Day 8
Secondary	Maximum plasma concentration (Cmax) of ACT-541468	Cmax was directly derived from the observed plasma concentrations of ACT-541468 for each dose level	From pre-dose up to 168 hours post-dose
Secondary	Time to reach Cmax (tmax) of ACT-541468	tmax was directly derived from the observed plasma concentrations of ACT-541468 for each dose level	From pre-dose up to 168 hours post-dose
Secondary	Terminal half-life (t1/2) of ACT-541468	t1/2 was calculated from the terminal rate constant obtained from the plasma concentrations-time curves of ACT-541468, at each dose level	From pre-dose up to 168 hours post-dose
Secondary	Area under the plasma concentration-time curves [AUC(0-inf)] of ACT-541468	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	From pre-dose up to 168 hours post-dose
Secondary	Percentage of dose excreted in feces and urine	Percentage of oral dose of 14C-labeled ACT-541468 excreted in feces (FPE), urine (UPE) and both, as determined in the dose group 3	From pre-dose up to 168 hours post-dose
Secondary	Absolute bioavailability (F) of ACT-541468	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)	Up to 96 hours post-dose