First-in-man Study of Single Ascending Dose of a New Drug for Neurological Disorders

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

Study Overview

• Status: Completed
• Conditions: Healthy Subjects
• Intervention / Treatment: Drug: AC-083; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 72
• 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 45 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Signed informed consent
• Healthy on the basis of physical examination, electrocardiogram and laboratory tests.
• A subject who has a female partner of childbearing potential or a pregnant partner agrees to use a condom in combination with spermicide or a condom, respectively, from screening, during the entire study, and for at least 3 months after (the last) study drug intake
• Body mass index (BMI) of 18.0 to 29.9 kg/m2 (inclusive) at screening and Day -1.
• Systolic blood pressure (SBP) 100-140 mmHg, diastolic blood pressure (DBP) 50-90 mmHg, and pulse rate 50-90 bpm (inclusive), measured after 5 min in the supine position at screening and at Day -1.

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 cardiac condition or illness with a potential to increase the cardiac risk of the subject based on medical history, physical examination, or electrocardiogram (ECG) evaluations
• 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: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: AC-083, Single Ascending Dose; AC-083 administered at different single dose levels in a sequential manner, and in a maximum of 9 dose levels starting from 1 mg (number of cohorts and dose levels will depend on the safety and pharmacokinetic results of the previous cohort). Each dose level will be investigated in a new group of 8 healthy male subjects (6 on active drug and 2 on placebo)	Drug: AC-083; Hard gelatin capsules for oral administration formulated at a strengths of 1, 10 and 100 mg
Placebo Comparator: Placebo, Single Ascending Dose; Matched placebo administered as single ascending doses in parallel to AC-083	Drug: Placebo; Placebo capsules matching AC-083 capsules

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with adverse events (AEs)	Treatment-emergent AEs and treatment emergent serious AEs	From baseline to end of study (EOS) (up to Day 12)
Changes from baseline in supine blood pressure	Supine blood pressure (mmHg)	From baseline to EOS (up to Day 12)
Changes from baseline in electrocardiogram (ECG) variables	ECG variables are to be recorded at rest using a standard 12-lead ECG	From baseline to EOS (up to Day 12)
Changes from baseline in pulse rate	Pulse rate (bpm)	From baseline to EOS (up to Day 12)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum plasma concentration (Cmax) following single oral ascending doses	Cmax is derived from the observed plasma concentration-time curves	From pre-dose on Day 1 to up to Day 12
Time to reach Cmax (tmax) following single oral ascending doses	Tmax is derived from the observed plasma concentration-time curves	From pre-dose on Day 1 to up to Day 12
Terminal half-life [t(1/2)] following single oral ascending doses		From pre-dose on Day 1 to up to Day 12
Area under the plasma concentration-time curve (AUC) following single oral ascending doses	AUC is defined for the time intervals from zero to time t of the last measured concentration above the limit of quantification, from zero to infinity and from zero to 24 h after study drug administration	From pre-dose on Day 1 to up to Day 12

Collaborators and Investigators

• Sponsor: Idorsia Pharmaceuticals Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): February 19, 2016
• Primary Completion (Actual): December 1, 2016
• Study Completion (Actual): December 1, 2016

Study Registration Dates

• First Submitted: March 14, 2016
• First Submitted That Met QC Criteria: March 21, 2016
• First Posted (Estimate): March 25, 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

• Additional Relevant MeSH Terms: Nervous System Diseases
• Other Study ID Numbers: AC-083-101; 2015-005012-15 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No