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

NCT03165097 | Completed Phase 1

• 2 other identifiers: AC-083-1022017-000336-34
• Study Type: interventional
• Target: 46
• Locations: 1 country
• Sites: 1

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

Conditions

Healthy Subjects

Keywords

tolerability; safety

Outcome Measures

Primary Outcomes (3)

• Incidence of treatment-emergent adverse events

  The percentage of subjects with treatment-emergent adverse events will be reported

  up to Day 23

• Changes from baseline in vital signs

  Vital signs include diastolic and systolic blood pressure and pulse rate

  up to Day 23

• 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 Outcomes (7)

• Maximum plasma concentration (Cmax) of ACT-709478

  up to Day 23

• Time to reach Cmax (tmax) of ACT-709478

  up to Day 23

• Terminal half-life (t1/2) of ACT-709478

  up to Day 23

• Area under the plasma concentration-time curve AUC(tau) of ACT-709478

  up to Day 23

• Area under the plasma concentration-time curve AUC(tau) of midazolam

  24 hours after dosing on Day 1, Day 22 and Day 30

Study Arms (4)

ACT-709478

EXPERIMENTAL

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.

Drug: ACT-709478

Placebo

PLACEBO COMPARATOR

Matched placebo administered accordingly

Drug: Placebo

Midazolam

OTHER

4 mg taken by mouth on Day 1 of the corresponding cohort

Drug: Midazolam

ACT-709478 combined with Midazolam

EXPERIMENTAL

On Day 22 and Day 30, midazolam (4 mg) and ACT-709478 (60 mg or 100 mg) to be co-administered.

Drug: ACT-709478 combined with midazolam

Interventions

ACT-709478 DRUG

Hard gelatine capsules for oral administration

ACT-709478

Placebo DRUG

Placebo capsules matching ACT-709478 capsules

Placebo

Midazolam DRUG

Midazolam oral solution (2 mg/mL) applied with a syringe

Midazolam

ACT-709478 combined with midazolam DRUG

Hard gelatine capsules for oral administration (ACT-709478) to be taken first followed by Midazolam oral solution (2 mg/mL) applied with a syringe

ACT-709478 combined with Midazolam

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Idorsia Pharmaceuticals Ltd.: lead

Study Sites (1)

Parexel

Berlin, 14050, Germany

Location

Related Publications (1)

• 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.

  PMID: 31994022 DERIVED

MeSH Terms

Interventions

ACT-709478; Midazolam

Intervention Hierarchy (Ancestors)

Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Study Director

  Idorsia Pharmaceuticals Ltd.

  STUDY DIRECTOR

Study Design

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

Study Record Dates

• First Submitted: May 23, 2017
• First Posted: May 24, 2017
• Study Start: July 7, 2017
• Primary Completion: November 15, 2018
• Study Completion: December 28, 2018
• Last Updated: December 24, 2019

Record last verified: 2019-12

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)