A Study to Evaluate if AC-084 is Safe, Its Fate in the Body as Well as Its Potential Effects on the Body in Healthy Subjects

A Three-part Single-center, Phase 1 Study to Assess the Tolerability, Safety, Pharmacokinetics (Including Food Interaction), and Pharmacodynamics of Ascending Single and Multiple Doses of AC-084 in Healthy Subjects and to Investigate the Pharmacokinetics of a Single Dose of AC-084 in Healthy CYP2C9 Poor Metabolizers

The primary purpose of this first-in-man study is to investigate whether AC-084 is safe and well-tolerated when orally administered at single- and multiple-ascending dose to healthy adults

Study Overview

• Status: Terminated
• Conditions: Healthy Subjects
• Intervention / Treatment: Drug: AC-084; Drug: Placebo

Detailed Description

The study is designed in three parts, A, B and C

Part A: single-center, double-blind, randomized, placebo-controlled, single ascending dose

Part B: single-center, double-blind, randomized, placebo-controlled, multiple ascending dose

Part C: single-center, open-label, single dose in CYP2C9 poor metabolizers

• Study Type: Interventional
• Enrollment (Actual): 56
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • Leeds, United Kingdom, LS2 9LH
    • Covance Clinical Research Unit

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Signed informed consent in the local language prior to any study-mandated procedure
• Healthy male subjects for Part A, healthy male and female subjects for Part B and Part C aged between 18 and 55 years (inclusive) at screening
• No clinically significant findings on physical examination at screening
• Body mass index (BMI) of 18.0 to 28.0 kg/m2 (inclusive) at screening
• CYP2C9 poor metabolizers (Part C)

Exclusion Criteria:

• History or clinical evidence of any disease and/or existence of any surgical or medical condition that might interfere with the absorption, distribution, metabolism or excretion of the study treatment (appendectomy and herniotomy allowed, cholecystectomy not allowed)
• Previous history of fainting, collapse, syncope, orthostatic hypotension, or vasovagal reactions
• Treatment or substances known to induce CYP enzyme drug metabolism within 30 days prior to first study treatment administration
• Any circumstances or conditions, which, in the opinion of the investigator, may affect full participation in the study or compliance with the protocol
• Known allergic reactions or hypersensitivity to the study treatment or drugs of the same class, or any of their excipients
• For Part A and Part B, CYP2C9 poor metabolizers enrolled in a cohort to be dosed with single or multiple dose of 500 mg or higher of ACT-774312 (confirmed by genotyping before enrollment)

Study Plan

How is the study designed?

Design Details

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

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: AC-084, single ascending dose (Part A); AC-084 administered at different single dose levels in a sequential manner, and in a maximum of 7 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 at least 8 healthy male subjects (6 on active drug and 2 on placebo)	Drug: AC-084; Hard gelatin capsules for oral administration formulated in strengths of 1 mg, 10 mg, and 100 mg
Placebo Comparator: Placebo,single ascending dose (Part A); Matched placebo administered as single ascending doses in parallel to AC-084	Drug: Placebo; Placebo capsules matching AC-084 capsules
Experimental: AC-084, multiple ascending dose (Part B); AC-084 administered in a twice daily (b.i.d.) dosing regimen at multiple dose levels. The starting dose will be between 1 and 30 mg and will be selected on the basis of the safety and pharmacokinetic results of the part A. Each dose level will be investigated in a new group of at least 8 healthy male subjects (6 on active drug and 2 on placebo)	Drug: AC-084; Hard gelatin capsules for oral administration formulated in strengths of 1 mg, 10 mg, and 100 mg
Placebo Comparator: Placebo,multiple ascending dose (Part B); Matched placebo administered as multiple ascending doses in parallel to AC-084	Drug: Placebo; Placebo capsules matching AC-084 capsules
Experimental: AC-084, single dose (Part C); Up to 6 subjects in part C will receive AC-084 administered at a single dose (foreseen to be 100 mg)	Drug: AC-084; Hard gelatin capsules for oral administration formulated in strengths of 1 mg, 10 mg, and 100 mg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with adverse events (AEs) (Part A)	Treatment-emergent AEs and treatment-emergent serious AEs	From dosing until day 4
Number of participants with adverse events (AEs) (Part B)	Treatment-emergent AEs and treatment-emergent serious AEs	From dosing until day 8
Number of participants with adverse events (AEs) (Part C)	Treatment-emergent AEs and treatment-emergent serious AEs	From dosing until day 6
Incidence of safety events of interest (Part A)	Events of interest are any abnormalities in ECG, vital signs or laboratory test results	From dosing until day 4
Incidence of safety events of interest (Part B)	Events of interest are any abnormalities in ECG, vital signs or laboratory test results	From dosing until day 8
Incidence of safety events of interest (Part C)	Events of interest are any abnormalities in ECG, vital signs or laboratory test results	From dosing until day 6

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum plasma concentration (Cmax) following single oral ascending doses (Part A)	Cmax is derived from the observed plasma concentration-time curves	From dosing until day 4
Maximum plasma concentration (Cmax) following single oral ascending doses (Part B)	Cmax is derived from the observed plasma concentration-time curves	From dosing until day 8
Maximum plasma concentration (Cmax) following single oral ascending doses (Part C)	Cmax is derived from the observed plasma concentration-time curves	From dosing until day 6
Time to reach Cmax (tmax) following single oral ascending doses (Part A)	Tmax is derived from the observed plasma concentration-time curves	From dosing until day 4
Time to reach Cmax (tmax) following single oral ascending doses (Part B)	Tmax is derived from the observed plasma concentration-time curves	From dosing until day 8
Time to reach Cmax (tmax) following single oral ascending doses (Part C)	Tmax is derived from the observed plasma concentration-time curves	From dosing until day 6
Terminal half-life [t(1/2)] following single oral ascending doses (Part A)		From dosing until day 4
Terminal half-life [t(1/2)] following single oral ascending doses (Part B)		From dosing until day 8
Terminal half-life [t(1/2)] following single oral ascending doses (Part C)		From dosing until day 6
Area under the plasma concentration-time curve (AUC) following single oral ascending doses (Part A)	AUC is defined for the time intervals from zero to time t of the last measured concentration above the limit of quantification and from zero to infinity	From dosing until day 4
Area under the plasma concentration-time curve (AUC) following single oral ascending doses (Part B)	AUC is defined for the time intervals from zero to time t of the last measured concentration above the limit of quantification and from zero to infinity	From dosing until day 8
Area under the plasma concentration-time curve (AUC) following single oral ascending doses (Part C)	AUC is defined for the time intervals from zero to time t of the last measured concentration above the limit of quantification and from zero to infinity	From dosing until day 6

Collaborators and Investigators

• Sponsor: Idorsia Pharmaceuticals Ltd.
• Investigators: Study Director: Martine Géhin, PhD, Actelion

Study record dates

Study Major Dates

• Study Start (Actual): September 12, 2016
• Primary Completion (Actual): December 10, 2017
• Study Completion (Actual): December 10, 2017

Study Registration Dates

• First Submitted: August 31, 2016
• First Submitted That Met QC Criteria: September 14, 2016
• First Posted (Estimate): September 19, 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

• Other Study ID Numbers: AC-084-101