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| ID | Type | Description | Link |
|---|---|---|---|
| 2016-000811-34 | EudraCT Number |
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The primary objectives of this 2-part drug interaction study are as follows:
Because non-clinical studies have shown that selexipag and its active metabolite, ACT-333679, are substrates for cytochrome P450 2C8 (CYP2C8), the present clinical study aims at investigating the effect of a strong inhibitor (gemfibrozil) and a moderate inducer (rifampicin) of CYP2C8 on the pharmacokinetic of selexipag and ACT-333679 as recommended by the FDA's Guidance for Industry Drug Interaction Studies (FDA, 2012).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Part 1, sequence AB | Experimental | Subjects participate in two study periods: During the first period (Treatment A), they receive oral selexipag on Day 1. During the second period (Treatment B), they receive multiple oral dose of gemfibrozil from Day 1 to Day 9. Subjects also receive a single oral dose of selexipag on Day 4 concomitantly with gemfibrozil. There is a washout period of 14 to 21 days between the two periods. |
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| Part 1, sequence BA | Experimental | Subjects participate in two study periods: During the first period (Treatment B), they receive multiple oral dose of gemfibrozil from Day 1 to Day 9. They also receive a single oral dose of selexipag on Day 4 concomitantly with gemfibrozil. During the second period (Treatment A) they receive oral selexipag on Day 1. There is a washout period of 14 to 21 days between the two periods. |
|
| Part 2, sequence AB | Experimental | Subjects participate in two study periods: During the first period (Treatment A), they receive oral selexipag on Day 1. During the second period (Treatment B), they receive rifampicin once daily from Day 1 to Day 9. Subjects also receive a single oral dose of selexipag on Day 7 together with the dose of rifampicin.There is a washout period of 14 to 21 days between the two periods. |
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| Part 2, sequence BA | Experimental | Subjects participate in two study periods: During the first period (Treatment B), they receive rifampicin once daily from Day 1 to Day 9. Subjects also receive a single oral dose of selexipag on Day 7 together with the dose of rifampicin. During the second period (Treatment A), they receive oral selexipag on Day 1. There is a washout period of 14 to 21 days between the two periods. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Selexipag | Drug | Two selexipag film-coated tablets of 200 µg as single oral dose (total dose = 400 µg) |
|
| Measure | Description | Time Frame |
|---|---|---|
| Area under the plasma concentration-time curve from zero to infinity [AUC(0-inf)] of selexipag and ACT-333679 | AUC(0-inf) is calculated for selexipag and its metabolite, ACT-333679, following administration of selexipag alone or concomitantly with gemfibrozil (Part I) or rifampicin (Part II) | Blood samples at different time points from pre-dose up to 72 hours after selexipag administration in each study period (except for the period with co-administration of gemfibrozil: up to 144 hours) |
| Maximum plasma concentration (Cmax) of selexipag and ACT-333679 | Cmax is directly derived from the individual plasma concentration-time curves for selexipag and its metabolite, ACT-333679, following administration of selexipag alone or concomitantly with gemfibrozil (Part I) or rifampicin (Part II) | Blood samples at different time points from pre-dose up to 72 hours after selexipag administration in each study period (except for the period with co-administration of gemfibrozil: up to 144 hours) |
| Measure | Description | Time Frame |
|---|---|---|
| Area under the plasma concentration-time curve from zero to time t of the last measured concentration above the limit of quantification [(AUC(0-t)] of selexipag and ACT-333679 | AUC(0-t) is calculated for selexipag and ACT-333679,following administration of selexipag alone or concomitantly with gemfibrozil (Part I) or rifampicin (Part II) | Blood samples at different time points from pre-dose up to 72 hours after selexipag administration in each study period (except for the period with co-administration of gemfibrozil: up to 144 hours) |
| Measure | Description | Time Frame |
|---|---|---|
| Incidence of treatment-emergent adverse events and serious adverse events | A treatment-emergent AE is any AE temporally associated with the use of a study treatment, whether or not considered related to the study treatment | Up to 35 days (from first study drug administration to end of study visit) |
| Incidence of safety events of interest |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Shirin Bruderer, PhD | Actelion | Study Director |
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| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 28715853 | Derived | Bruderer S, Petersen-Sylla M, Boehler M, Remenova T, Halabi A, Dingemanse J. Effect of gemfibrozil and rifampicin on the pharmacokinetics of selexipag and its active metabolite in healthy subjects. Br J Clin Pharmacol. 2017 Dec;83(12):2778-2788. doi: 10.1111/bcp.13379. Epub 2017 Aug 16. |
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| ID | Term |
|---|---|
| C523468 | selexipag |
| D015248 | Gemfibrozil |
| D012293 | Rifampin |
| ID | Term |
|---|---|
| D058607 | Fibric Acids |
| D058610 | Isobutyrates |
| D002087 | Butyrates |
| D000144 | Acids, Acyclic |
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| Gemfibrozil | Drug | Gemfibrozil film-coated tablet of 600 mg administered orally b.i.d. from Day 1 to Day 9 |
|
| Rifampicin | Drug | Rifampicin film-coated tablet of 600 mg administered orally o.d.from Day 1 to Day 9 |
|
| Time to reach maximum plasma concentration (tmax) of selexipag and ACT-333679 | tmax is directly derived from the individual plasma concentration-time curves for selexipag and its metabolite, ACT-333679, following administration of selexipag alone or concomitantly with gemfibrozil (Part I) or rifampicin (Part II) | Blood samples at different time points from pre-dose up to 72 hours after selexipag administration in each study period (except for the period with co-administration of gemfibrozil: up to 144 hours) |
| Terminal elimination half-life (t1/2) of selexipag and ACT-333679 | t1/2 is the period of time required for the concentration levels of selexipag or ACT-333679 to be reduced by one-half, following administration of selexipag alone or concomitantly with gemfibrozil (Part I) or rifampicin (Part II) | Blood samples at different time points from pre-dose up to 72 hours after selexipag administration in each study period (except for the period with co-administration of gemfibrozil: up to 144 hours) |
Include any abnormalities in ECG, vital signs or laboratory test results |
| Up to 35 days (from first study drug administration to end of study visit) |
| D002264 |
| Carboxylic Acids |
| D009930 | Organic Chemicals |
| D010421 | Pentanoic Acids |
| D014631 | Valerates |
| D010647 | Phenyl Ethers |
| D004987 | Ethers |
| D010636 | Phenols |
| D001555 | Benzene Derivatives |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D005232 | Fatty Acids, Volatile |
| D005227 | Fatty Acids |
| D008055 | Lipids |
| D012294 | Rifamycins |
| D006576 | Heterocyclic Compounds, 4 or More Rings |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
| D047029 | Lactams, Macrocyclic |
| D047028 | Macrocyclic Compounds |
| D011083 | Polycyclic Compounds |