Study to Evaluate Safety and Tolerability of ACT-709478 in Healthy Subjects
Study Details
Study Description
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
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: 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. |
Drug: ACT-709478
Hard gelatine capsules for oral administration
|
| Placebo Comparator: Placebo Matched placebo administered accordingly |
Drug: Placebo
Placebo capsules matching ACT-709478 capsules
|
| Other: Midazolam 4 mg taken by mouth on Day 1 of the corresponding cohort |
Drug: Midazolam
Midazolam oral solution (2 mg/mL) applied with a syringe
|
| Experimental: 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. |
Drug: 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
|
Outcome Measures
Primary Outcome Measures
- 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
- Maximum plasma concentration (Cmax) of ACT-709478 [up to Day 23]
Cmax is derived from the observed plasma concentration-time curves
- 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
- 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
- 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
- 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
Eligibility Criteria
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
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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
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Any circumstances or conditions, which, in the opinion of the investigator, may affect full participation in the study or compliance with the protocol
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Parexel | Berlin | Germany | 14050 |
Sponsors and Collaborators
- Idorsia Pharmaceuticals Ltd.
Investigators
- Study Director: Study Director, Idorsia Pharmaceuticals Ltd.
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- AC-083-102
- 2017-000336-34