Study to Evaluate Safety and Tolerability of ACT-709478 in Healthy Subjects

Phase 1

Completed

• Conditions: Healthy Subjects
• Interventions: Drug: Placebo; Drug: Midazolam; Drug: ACT-709478 combined with midazolam; Drug: ACT-709478

• Registration Number: NCT03165097
• Lead Sponsor: Idorsia Pharmaceuticals Ltd.

Brief Summary

The primary purpose of this study is to evaluate the safety and tolerability of ascending multiple doses of ACT-709478 in healthy male and female subjects

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2017-05-23
• Study First Submitted QC: 2017-05-23
• Study First Posted: 2017-05-24
• Study Start: 2017-07-07
• Primary Completion: 2018-11-15
• Study Completion: 2018-12-28
• Status Verified: 2019-12
• Last Update Submitted: 2019-12-20
• Last Update Posted: 2019-12-24

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 46

Inclusion Criteria

• Signed informed consent form
• Healthy male and female subjects aged between 18 and 55 years (inclusive) at screening
• Negative serum pregnancy tests at screening and negative urine pregnancy test at Day -1 for women and agreement to use 2 reliable methods of contraception for at least 3 months after last study drug administration
• Body mass index of 18.0 to 29.9 kg/m2 (inclusive) at screening
• Systolic blood pressure 100-140 mmHg, diastolic blood pressure 50-90 mmHg, and pulse rate 50-90 bpm (inclusive), measured after 5 minutes in the supine position at screening and on Day -1
• Healthy on the basis of physical examination, cardiovascular, ophthalmological, neurological assessments and laboratory tests

Exclusion Criteria

• Known hypersensitivity to ACT-709478 or drugs of the same class, or any of their excipients
• History or clinical evidence of any disease and/or existence of any surgical or medical condition, which might interfere with the absorption, distribution, metabolism, or excretion of the study treatments
• QT interval corrected with Fridericia's formula (QTcF) > 450 ms (using the ECG machine HR correction method) at screening and on Day -1
• Treatment with another investigational treatment within 2 months or 5 t1/2 (whichever is the longest) prior to screening or participation in more than four investigational treatment studies within 1 year prior to screening
• Any circumstances or conditions, which, in the opinion of the investigator, may affect full participation in the study or compliance with the protocol

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Matched placebo administered accordingly
Midazolam	Midazolam	4 mg taken by mouth on Day 1 of the corresponding cohort
ACT-709478 combined with Midazolam	ACT-709478 combined with midazolam	On Day 22 and Day 30, midazolam (4 mg) and ACT-709478 (60 mg or 100 mg) to be co-administered.
ACT-709478	ACT-709478	40 subjects will receive multiple doses of ACT-709478 at the planned dose levels of 30, 60, 100, and 200 mg. Each dose level will be investigated in a new cohort of 10 healthy male and female subjects (4 male subjects on active drug and 1 on placebo, 4 female subjects on active drug and 1 on placebo) undergoing one treatment period with a once daily dosing scheme.

Primary Outcome Measures

Name	Time	Method
Incidence of treatment-emergent adverse events	up to Day 23	The percentage of subjects with treatment-emergent adverse events will be reported
Changes from baseline in vital signs	up to Day 23	Vital signs include diastolic and systolic blood pressure and pulse rate
Incidence of any clinical relevant findings in ECG variables	up to Day 23	The number of subjects with any treatment-emergent electrocardiogram (ECG) abnormalities will be reported

Secondary Outcome Measures

Name	Time	Method
Area under the plasma concentration-time curve AUC(tau) of ACT-709478	up to Day 23	AUCtau is defined as the area under the plasma concentration-time curve during one dosing interval
Time to reach Cmax (tmax) of ACT-709478	up to Day 23	tmax is directly derived from the observed plasma concentrations
Terminal half-life (t1/2) of ACT-709478	up to Day 23	t1/2 is calculated from the terminal rate constant obtained from the plasma concentrations-time curves
Maximum plasma concentration (Cmax) of ACT-709478	24 hours after dosing on Day 1, Day 22 and Day 30	Cmax is derived from the observed plasma concentration-time curves
Area under the plasma concentration-time curve AUC(tau) of midazolam	24 hours after dosing on Day 1, Day 22 and Day 30	AUCtau is defined as the area under the plasma concentration-time curve during one dosing interval
Time to reach Cmax (tmax)	24 hours after dosing on Day 1, Day 22 and Day 30	tmax is directly derived from the observed plasma concentrations

Trial Locations

Locations (1)

Parexel; 🇩🇪 Berlin, Germany