First-in-man Study of Single and Multiple Ascending Doses of a New Drug for Neurological Disorders

Single-center, Double-blind, Randomized, Placebo-controlled, Single and Multiple Ascending Dose Study to Investigate the Safety, Tolerability, Pharmacokinetics (Including Food Effect), and Pharmacodynamics of an Oral Drug for Neurological Disorders in Healthy Subjects

The primary purpose of this first-in-man study is to investigate whether a new drug for neurological disorders is safe and well-tolerated when administered orally to healthy adults

Study Overview

• Status: Completed
• Conditions: Healthy Subjects
• Intervention / Treatment: Drug: AC-082; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 128
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Berlin, Germany, 14050
    • Investigator site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Key inclusion Criteria:

• Signed informed consent
• Healthy on the basis of physical examination,12-lead electrocardiogram and laboratory tests
• Males and females of non-childbearing potential, aged between 18 and 60 years (all inclusive)
• Women must have a negative serum pregnancy test at Screening and a negative urine pregnancy test predose on Day -1
• Body mass index (BMI) between 18.0 and 29.9 kg/m2 (inclusive)
• Systolic blood pressure (SBP), diastolic blood pressure (DBP) and pulse rate (PR) between 90-140 mmHg, 50-90 mmHg and 50-90 bpm (all inclusive), respectively

Key exclusion Criteria:

• History or clinical evidence of any disease and/or existence of any surgical or medical condition which might interfere with the absorption, distribution, metabolism or excretion of the study treatment
• Previous history of fainting, collapse, syncope, orthostatic hypotension, or vasovagal reactions
• Any circumstances or conditions, which, in the opinion of the Investigator, may affect full participation in the study or compliance with the protocol

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: AC-082, Single Ascending Dose; Subjects receive AC-082 at different single dose levels in a sequential manner, starting from 10 mg (number of cohorts and dose levels will depend on the safety and pharmacokinetic results of the previous cohort). Each subject can participate in only one dose level	Drug: AC-082; Hard gelatin capsules for oral administration
Placebo Comparator: Placebo, Single Ascending Dose; Subjects receive a single dose of the matched placebo	Drug: Placebo; Matched placebo capsules for oral administration
Experimental: AC-082, Multiple Ascending Dose; Subjects receive AC-082 at different dose levels for 4 consecutive days in a sequential manner (dose levels and duration to be adapted according to the results of the single ascending dose cohorts). Each subject can participate in only one dose level	Drug: AC-082; Hard gelatin capsules for oral administration
Placebo Comparator: Placebo, Multiple Ascending Dose; Subjects receive the matched placebo for 4 days	Drug: Placebo; Matched placebo capsules for oral administration

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with adverse events (AEs)	Treatment-emergent adverse events and treatment-emergent serious adverse events	Up to end of study (up to Day 11)
Changes from baseline in vital signs	Vital signs include diastolic and systolic blood pressure and pulse rate	Up to end of study (up to Day 11)
Changes from baseline in ECG variables	ECG variables are to be recorded at rest using a standard 12-lead ECG	Up to end of study (up to day 11)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum plasma concentration (Cmax) following single ascending doses	Cmax is derived from the observed plasma concentration-time curves	From pre-dose on Day 1 to 96 hours post dose
Time to reach Cmax (tmax) following single ascending doses	tmax is derived from the observed plasma concentration-time curves	From pre-dose on Day 1 to 96 hours post dose
Terminal half-life [t(1/2)] following single ascending doses		From pre-dose on Day 1 to 96 hours post dose
Area under the plasma concentration-time curve (AUC) following single ascending doses	AUC is defined for the time intervals from zero to time t of the last measured concentration above the limit of quantification [AUC(0-t)] and from zero to infinity [AUC(0-inf)]	From pre-dose on Day 1 to 96 hours post dose
Maximum plasma concentration (Cmax) following multiple ascending doses		Up to 96 hours following the last dose administration on Day 4
Time to reach Cmax (tmax) following multiple ascending doses		Up to 96 hours following the last dose administration on Day 4
Terminal half-life [t(1/2)] following multiple ascending doses	t(1/2) on the last day of dosing	Up to 96 hours following the last dose administration on Day 4
Area under the plasma concentration-time curve during a dosing interval (AUCtau)	AUCtau is the area under the plasma concentration-time curve during a dosing interval	Day 1 and Day 4

Collaborators and Investigators

• Sponsor: Idorsia Pharmaceuticals Ltd.
• Investigators: Study Director: Karine Litherland, PhD, Actelion

Study record dates

Study Major Dates

• Study Start: February 1, 2016
• Primary Completion (Actual): March 6, 2017
• Study Completion (Actual): March 6, 2017

Study Registration Dates

• First Submitted: February 24, 2016
• First Submitted That Met QC Criteria: March 3, 2016
• First Posted (Estimate): March 9, 2016

Study Record Updates

• Last Update Posted (Actual): July 10, 2018
• Last Update Submitted That Met QC Criteria: July 6, 2018
• Last Verified: July 1, 2018

More Information

Terms related to this study

• Keywords: safety; healthy subjects; first-in-man
• Additional Relevant MeSH Terms: Nervous System Diseases
• Other Study ID Numbers: AC-082-101