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

Phase 1

Terminated

• Conditions: Healthy Subjects
• Interventions: Drug: AC-084; Drug: Placebo

• Registration Number: NCT02905253
• Lead Sponsor: Idorsia Pharmaceuticals Ltd.

Brief Summary

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

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 Timeline

• Study First Submitted: 2016-08-31
• Study Start: 2016-09-12
• Study First Submitted QC: 2016-09-14
• Study First Posted: 2016-09-19
• Primary Completion: 2017-12-10
• Study Completion: 2017-12-10
• Status Verified: 2018-07
• Last Update Submitted: 2018-07-06
• Last Update Posted: 2018-07-10

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 56

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
AC-084, single ascending dose (Part A)	AC-084	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)
Placebo,single ascending dose (Part A)	Placebo	Matched placebo administered as single ascending doses in parallel to AC-084
Placebo,multiple ascending dose (Part B)	Placebo	Matched placebo administered as multiple ascending doses in parallel to AC-084
AC-084, single dose (Part C)	AC-084	Up to 6 subjects in part C will receive AC-084 administered at a single dose (foreseen to be 100 mg)
AC-084, multiple ascending dose (Part B)	AC-084	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)

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Maximum plasma concentration (Cmax) following single oral ascending doses (Part A)	From dosing until day 4	Cmax is derived from the observed plasma concentration-time curves
Maximum plasma concentration (Cmax) following single oral ascending doses (Part B)	From dosing until day 8	Cmax is derived from the observed plasma concentration-time curves
Maximum plasma concentration (Cmax) following single oral ascending doses (Part C)	From dosing until day 6	Cmax is derived from the observed plasma concentration-time curves
Time to reach Cmax (tmax) following single oral ascending doses (Part A)	From dosing until day 4	Tmax is derived from the observed plasma concentration-time curves
Time to reach Cmax (tmax) following single oral ascending doses (Part B)	From dosing until day 8	Tmax is derived from the observed plasma concentration-time curves
Time to reach Cmax (tmax) following single oral ascending doses (Part C)	From dosing until day 6	Tmax is derived from the observed plasma concentration-time curves
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
Area under the plasma concentration-time curve (AUC) following single oral ascending doses (Part A)	From dosing until day 4	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
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 B)	From dosing until day 8	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
Area under the plasma concentration-time curve (AUC) following single oral ascending doses (Part C)	From dosing until day 6	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

Trial Locations

Locations (1)

Covance Clinical Research Unit; 🇬🇧 Leeds, United Kingdom