Healthy Subjects
Conditions
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
Interventions
DRUGAC-084
Hard gelatin capsules for oral administration formulated in strengths of 1 mg, 10 mg, and 100 mg
DRUGPlacebo
Placebo capsules matching AC-084 capsules
Sponsors
Idorsia Pharmaceuticals Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 | — |
| 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 |
| 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 |
| 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 |
| 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 |
Countries
United Kingdom
Outcome results
None listed