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

NCT02905253 | Terminated Phase 1

• 1 other identifier: AC-084-101
• Study Type: interventional
• Target: 56
• Locations: 1 country
• Sites: 1

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

Conditions

Healthy Subjects

Outcome Measures

Primary Outcomes (6)

• 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 Outcomes (12)

• Maximum plasma concentration (Cmax) following single oral ascending doses (Part A)

  From dosing until day 4

• Maximum plasma concentration (Cmax) following single oral ascending doses (Part B)

  From dosing until day 8

• Maximum plasma concentration (Cmax) following single oral ascending doses (Part C)

  From dosing until day 6

• Time to reach Cmax (tmax) following single oral ascending doses (Part A)

  From dosing until day 4

• Time to reach Cmax (tmax) following single oral ascending doses (Part B)

  From dosing until day 8

Study Arms (5)

AC-084, single ascending dose (Part A)

EXPERIMENTAL

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

Placebo,single ascending dose (Part A)

PLACEBO COMPARATOR

Matched placebo administered as single ascending doses in parallel to AC-084

Drug: Placebo

AC-084, multiple ascending dose (Part B)

EXPERIMENTAL

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

Placebo,multiple ascending dose (Part B)

PLACEBO COMPARATOR

Matched placebo administered as multiple ascending doses in parallel to AC-084

Drug: Placebo

AC-084, single dose (Part C)

EXPERIMENTAL

Up to 6 subjects in part C will receive AC-084 administered at a single dose (foreseen to be 100 mg)

Drug: AC-084

Interventions

AC-084 DRUG

Hard gelatin capsules for oral administration formulated in strengths of 1 mg, 10 mg, and 100 mg

AC-084, multiple ascending dose (Part B); AC-084, single ascending dose (Part A); AC-084, single dose (Part C)

Placebo DRUG

Placebo capsules matching AC-084 capsules

Placebo,multiple ascending dose (Part B); Placebo,single ascending dose (Part A)

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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)

You may not qualify if:

• 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)

Sponsors & Collaborators

• Idorsia Pharmaceuticals Ltd.: lead

Study Sites (1)

Covance Clinical Research Unit

Leeds, LS2 9LH, United Kingdom

Location

Study Officials

• Martine Géhin, PhD

  Actelion

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 31, 2016
• First Posted: September 19, 2016
• Study Start: September 12, 2016
• Primary Completion: December 10, 2017
• Study Completion: December 10, 2017
• Last Updated: July 10, 2018

Record last verified: 2018-07

Locations

GB (1)