Clinical trial NCT03165097: Study to Evaluate Safety and Tolerability of ACT-709478 in Healthy Subjects
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Subjects
Keywords: tolerability
safety
Lead sponsor: Idorsia Pharmaceuticals Ltd.
Sponsor class: INDUSTRY
First posted: 2017-05-24
Enrollment: 46
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 study is to evaluate the safety and tolerability of ascending multiple doses of ACT-709478 in healthy male and female subjects


Eligibility criteria: 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

Primary outcomes:
measure: Incidence of treatment-emergent adverse events
timeFrame: up to Day 23
measure: Changes from baseline in vital signs
timeFrame: up to Day 23
measure: Incidence of any clinical relevant findings in ECG variables
timeFrame: up to Day 23
Secondary outcomes:
measure: Maximum plasma concentration (Cmax) of ACT-709478
timeFrame: up to Day 23
measure: Time to reach Cmax (tmax) of ACT-709478
timeFrame: up to Day 23
measure: Terminal half-life (t1/2) of ACT-709478
timeFrame: up to Day 23
measure: Area under the plasma concentration-time curve AUC(tau) of ACT-709478
timeFrame: up to Day 23
measure: Area under the plasma concentration-time curve AUC(tau) of midazolam
timeFrame: 24 hours after dosing on Day 1, Day 22 and Day 30
measure: Time to reach Cmax (tmax)
timeFrame: 24 hours after dosing on Day 1, Day 22 and Day 30
measure: Maximum plasma concentration (Cmax) of ACT-709478
timeFrame: 24 hours after dosing on Day 1, Day 22 and Day 30
Other outcomes:
Locations:
city: Berlin
country: Germany
facility: Parexel
Study officials:
affiliation: Idorsia Pharmaceuticals Ltd.
name: Study Director
role: STUDY_DIRECTOR
References:
citation: Richard M, Kaufmann P, Ort M, Kornberger R, Dingemanse J. Multiple-Ascending Dose Study in Healthy Subjects to Assess the Pharmacokinetics, Tolerability, and CYP3A4 Interaction Potential of the T-Type Calcium Channel Blocker ACT-709478, A Potential New Antiepileptic Drug. CNS Drugs. 2020 Mar;34(3):311-323. doi: 10.1007/s40263-019-00697-1.