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Based on results from the pilot phase, the study is terminated. No safety events leading to discontinuation were reported
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The aim of the study is to investigate the safety of the concomitant administration of ACT-334441 with cardiovascular drugs.
The study will consist of two parts: a pilot part (Part A) that will be completed prior to the start of the main part (Part B). The Subjects who will participate in Part A are excluded from Part B.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Part A ACT-334441 + atenolol | Experimental | 4 subjects will receive 50 mg of atenolol once daily for 6 days, and a concomitant single administration of ACT-334441 2 mg on Day 6 |
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| Part A ACT-334441 + diltiazem | Experimental | 4 subjects will receive 240 mg of diltiazem once daily for 6 days, and a concomitant single administration of ACT-334441 2 mg on Day 6 |
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| Part B ACT-334441 + atenolol | Experimental | 12 subjects will receive 50 mg of atenolol (once daily) from day 1 to day 15, placebo once on day 6, and ACT-334441 4 mg (once daily) from day 8 to day 15 |
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| Part B ACT-334441 + diltiazem | Experimental | 12 subjects will receive 240 mg of diltiazem (once daily) from day 1 to day 15, placebo once on day 6, and ACT-334441 4 mg (once daily) from day 8 to day 15 |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| ACT-334441 2 mg | Drug | capsule containing ACT-334441 at a strength of 2 mg |
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| Measure | Description | Time Frame |
|---|---|---|
| PR intervals measured by 12-lead ECG (Part A + Part B) | Absolute PR intervals and corresponding changes from baseline at the different days of measurement | Days 1 and 6 (Part A); Days 1, 6, 8, 9, 15, and 16 (Part B) |
| Heart rate (HR) measured by 12-lead ECG (PArt A + Part B) | Absolute heart rates at the different days of measurement | Days 1 and 6 (Part A); Days 1, 6, 8, 9, 15, and 16 (Part B) |
| Hourly mean heart rate (HR) measured by 24-hour Holter ECG | Absolute and change from baseline in hourly mean HR on each day of measurement | Days 1 and 6 (Part A); Days 1, 6, 8, 9, 15, and 16 (Part B |
| Measure | Description | Time Frame |
|---|---|---|
| Areas under the plasma concentration-time curves (AUC) for ACT-334441, diltiazem and atenolol (Part B) | AUCs will be calculated will be calculated according to the linear trapezoidal rule for the following periods: from zero to time t of the last measured concentration above the limit of quantification, from zero to 24h after study drug administration, from zero to infinity) | Blood samples from Day 1 to Day 20 for the PK profile of diltiazem and atenolol, and from Day 8 to Day 21 for the PK profile of ACT-334441. |
| Measure | Description | Time Frame |
|---|---|---|
| Lymphocyte count as a measure of immunomodulation (Part A + Part B) | Day 1, Day 6, Day 12 and Day 20 (Part A); Day 1 and Day 8 toDay 16 (Part B) |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Clinical Trials | Viatris Innovation GmbH | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| BIOTRIAL | Rennes | CS 34246 | France |
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| ACT-334441 4 mg | Drug | capsule containing ACT-334441 at a strength of 4 mg |
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| Placebo | Drug | ACT-33441-matching placebo |
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| Atenolol | Drug | film-coated tablet containing atenolol at a strength of 50 mg |
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| Diltiazem ER | Drug | film-coated tablet containing diltiazem at a strength of of 120 mg |
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| Maximum plasma concentration (Cmax) for ACT-334441, diltiazem and atenolol (Part B) | The measured individual concentrations of ACT-334441, diltiazem and atenolol will be used to obtain their respective Cmax | From Day 1 to Day 20 for diltiazem and atenolol; from Day 8 to Day 21 for ACT-33444. |
| Time to reach the maximum plasma concentration (tmax) for ACT-334441, diltiazem and atenolol (Part B) | The measured individual concentrations of ACT-334441, diltiazem and atenolol will be used to obtain their respective tmax | From Day 1 to Day 20 for diltiazem and atenolol; from Day 8 to Day 21 for ACT-33444 |
| Terminal half-life [t(1/2)] of ACT-334441, diltiazem and atenolol (Part B) | Time required for the plasma concentration of a drug to decrease by 50% in the final stage of its elimination | From Day 1 to Day 20 for diltiazem and atenolol; from Day 8 to Day 21 for ACT-33444 |
| Trough plasma levels (Ctrough) of of ACT-334441, diltiazem and atenolol (Part B) | Ctrough will be used to determine the attainment of steady state conditions | From Day 1 to Day 15 for diltiazem and atenolol; from Day 8 to Day 15 for ACT-33444 |
| Number of subjects with adverse events as a measure of safety | An AE is defined as any unfavorable and unintended sign, including an abnormal laboratory finding, symptom or disease, that occurs during the course of the study, whether or not considered related to the study drug | From baseline to end of study [Day 20-23 (Part A), Day 556-59 (Part B)] |
| ID | Term |
|---|---|
| D001262 | Atenolol |
| ID | Term |
|---|---|
| D050198 | Phenoxypropanolamines |
| D011412 | Propanolamines |
| D000605 | Amino Alcohols |
| D000438 | Alcohols |
| D009930 | Organic Chemicals |
| D020005 | Propanols |
| D000588 | Amines |
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