Clinical trial NCT02905253: 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
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Healthy Subjects
Lead sponsor: Idorsia Pharmaceuticals Ltd.
Sponsor class: INDUSTRY
First posted: 2016-09-19
Enrollment: 56
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

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

Eligibility criteria: 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)

Primary outcomes:
measure: Number of participants with adverse events (AEs) (Part A)
timeFrame: From dosing until day 4
measure: Number of participants with adverse events (AEs) (Part B)
timeFrame: From dosing until day 8
measure: Number of participants with adverse events (AEs) (Part C)
timeFrame: From dosing until day 6
measure: Incidence of safety events of interest (Part A)
timeFrame: From dosing until day 4
measure: Incidence of safety events of interest (Part B)
timeFrame: From dosing until day 8
measure: Incidence of safety events of interest (Part C)
timeFrame: From dosing until day 6
Secondary outcomes:
measure: Maximum plasma concentration (Cmax) following single oral ascending doses (Part A)
timeFrame: From dosing until day 4
measure: Maximum plasma concentration (Cmax) following single oral ascending doses (Part B)
timeFrame: From dosing until day 8
measure: Maximum plasma concentration (Cmax) following single oral ascending doses (Part C)
timeFrame: From dosing until day 6
measure: Time to reach Cmax (tmax) following single oral ascending doses (Part A)
timeFrame: From dosing until day 4
measure: Time to reach Cmax (tmax) following single oral ascending doses (Part B)
timeFrame: From dosing until day 8
measure: Time to reach Cmax (tmax) following single oral ascending doses (Part C)
timeFrame: From dosing until day 6
measure: Terminal half-life [t(1/2)] following single oral ascending doses (Part A)
timeFrame: From dosing until day 4
measure: Terminal half-life [t(1/2)] following single oral ascending doses (Part B)
timeFrame: From dosing until day 8
measure: Terminal half-life [t(1/2)] following single oral ascending doses (Part C)
timeFrame: From dosing until day 6
measure: Area under the plasma concentration-time curve (AUC) following single oral ascending doses (Part A)
timeFrame: From dosing until day 4
measure: Area under the plasma concentration-time curve (AUC) following single oral ascending doses (Part B)
timeFrame: From dosing until day 8
measure: Area under the plasma concentration-time curve (AUC) following single oral ascending doses (Part C)
timeFrame: From dosing until day 6
Other outcomes:
Locations:
city: Leeds
country: United Kingdom
facility: Covance Clinical Research Unit
Study officials:
affiliation: Actelion
name: Martine Géhin, PhD
role: STUDY_DIRECTOR
References: