A Single Ascending Dose Study of ACT-541468 in Healthy Male Subjects
- Conditions
- Healthy Subjects
- Interventions
- Drug: Placebo (Formulation A)Drug: Placebo (Formulation B)Drug: Placebo tracer
- Registration Number
- NCT02919319
- Lead Sponsor
- 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.
- 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).
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Male
- Target Recruitment
- 40
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Dose group 1 ACT-541468 (Formulation A) Six subjects received 5 mg of ACT-541468 (formulation A) as a single oral dose and two subjects received the matching placebo. Dose group 1 Placebo (Formulation A) Six subjects received 5 mg of ACT-541468 (formulation A) as a single oral dose and two subjects received the matching placebo. Dose group 2 Placebo (Formulation A) 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. Dose group 2 Placebo (Formulation B) 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. Dose group 3 Placebo (Formulation A) 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. Dose group 3 14C-labeled ACT-541468 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. Dose group 3 Placebo tracer 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. Dose group 4 Placebo (Formulation A) 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. Dose group 5 ACT-541468 (Formulation A) Six subjects received 200 mg of ACT-541468 (formulation A) as a single oral dose and two subjects received the matching placebo. Dose group 5 Placebo (Formulation A) Six subjects received 200 mg of ACT-541468 (formulation A) as a single oral dose and two subjects received the matching placebo. Dose group 4 Placebo tracer 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. Dose group 4 ACT-541468 (Formulation A) 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. Dose group 2 ACT-541468 (Formulation A) 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. Dose group 2 ACT-541468 (Formulation B) 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. Dose group 3 ACT-541468 (Formulation A) 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. Dose group 4 14C-labeled ACT-541468 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.
- Primary Outcome Measures
Name Time Method Number of subjects with treatment-emergent adverse events and serious adverse events Day 8 Collection of any adverse event at each dose level
- Secondary Outcome Measures
Name Time Method Maximum plasma concentration (Cmax) of ACT-541468 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
Time to reach Cmax (tmax) of ACT-541468 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
Terminal half-life (t1/2) of ACT-541468 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
Area under the plasma concentration-time curves [AUC(0-inf)] of ACT-541468 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
Percentage of dose excreted in feces and urine 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
Absolute bioavailability (F) of ACT-541468 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)
Trial Locations
- Locations (1)
Investigator Site
🇳🇱Leiden, Netherlands