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

Healthy Subjects Clinical Trial

Official title:

A Single-center, Double-blind, Parallel-group, Randomized, Placebo-controlled, Multiple-ascending Oral Dose Study to Investigate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of ACT-709478 in Healthy Subjects

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03165097
• Other study ID #: AC-083-102
• Secondary ID: 2017-000336-34
• Status: Completed
• Phase: Phase 1
• Start date: July 7, 2017
• Est. completion date: December 28, 2018

Study information

• Verified date: December 2019
• Source: Idorsia Pharmaceuticals Ltd.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 46
• Est. completion date: December 28, 2018
• Est. primary completion date: November 15, 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

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

Related Conditions & MeSH terms

• Healthy Subjects

Intervention

Drug:
• ACT-709478
Hard gelatine capsules for oral administration
• Placebo
Placebo capsules matching ACT-709478 capsules
• Midazolam
Midazolam oral solution (2 mg/mL) applied with a syringe
• ACT-709478 combined with midazolam
Hard gelatine capsules for oral administration (ACT-709478) to be taken first followed by Midazolam oral solution (2 mg/mL) applied with a syringe

Locations

Country	Name	City	State
Germany	Parexel	Berlin

Sponsors (1)

Lead Sponsor	Collaborator
Idorsia Pharmaceuticals Ltd.

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of treatment-emergent adverse events	The percentage of subjects with treatment-emergent adverse events will be reported	up to Day 23
Primary	Changes from baseline in vital signs	Vital signs include diastolic and systolic blood pressure and pulse rate	up to Day 23
Primary	Incidence of any clinical relevant findings in ECG variables	The number of subjects with any treatment-emergent electrocardiogram (ECG) abnormalities will be reported	up to Day 23
Secondary	Maximum plasma concentration (Cmax) of ACT-709478	Cmax is derived from the observed plasma concentration-time curves	up to Day 23
Secondary	Time to reach Cmax (tmax) of ACT-709478	tmax is directly derived from the observed plasma concentrations	up to Day 23
Secondary	Terminal half-life (t1/2) of ACT-709478	t1/2 is calculated from the terminal rate constant obtained from the plasma concentrations-time curves	up to Day 23
Secondary	Area under the plasma concentration-time curve AUC(tau) of ACT-709478	AUCtau is defined as the area under the plasma concentration-time curve during one dosing interval	up to Day 23
Secondary	Area under the plasma concentration-time curve AUC(tau) of midazolam	AUCtau is defined as the area under the plasma concentration-time curve during one dosing interval	24 hours after dosing on Day 1, Day 22 and Day 30
Secondary	Time to reach Cmax (tmax)	tmax is directly derived from the observed plasma concentrations	24 hours after dosing on Day 1, Day 22 and Day 30
Secondary	Maximum plasma concentration (Cmax) of ACT-709478	Cmax is derived from the observed plasma concentration-time curves	24 hours after dosing on Day 1, Day 22 and Day 30