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| ID | Type | Description | Link |
|---|---|---|---|
| CA27858 | Other Identifier | Celerion |
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| Name | Class |
|---|---|
| Achillion, a wholly owned subsidiary of Alexion | INDUSTRY |
| Celerion | INDUSTRY |
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This was a 3-part study (Part 1, Part 2, Part 3) with each part being an open-label, fixed sequence, 2-period study in healthy adult participants.
This study was conducted to assess the 2-way interaction between danicopan and warfarin (Part 1), bupropion (Part 2), and ethinyl estradiol/norethindrone (EE/NET) as an oral contraceptive (Part 3).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Part 1: Danicopan and Warfarin | Experimental | Period 1: Participants received a single dose of warfarin. Period 2: Participants received danicopan three times daily, in addition to coadministration with a single dose of warfarin. Scheduled pharmacokinetics (PK) and pharmacodynamics samples were collected, with a washout period of at least 14 days between the dose of warfarin in Period 1 and the first dose of danicopan in Period 2. |
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| Part 2: Danicopan and Bupropion | Experimental | Period 1: Participants received a single dose of bupropion. Period 2: Participants received danicopan three times daily, in addition to coadministration with a single dose of bupropion. Scheduled PK samples were collected, with a washout period of at least 7 days between the dose of bupropion in Period 1 and the first dose of danicopan in Period 2. |
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| Part 3: Danicopan and EE/NET | Experimental | Period 1: Participants received a single dose of EE/NET. Period 2: Participants received danicopan three times daily, in addition to coadministration with a single dose of EE/NET. Scheduled PK samples were collected, with a washout period of at least 7 days between the dose of EE/NET in Period 1 and the first dose of danicopan in Period 2. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Danicopan | Drug | Danicopan was dosed as 2 x 100 milligram (mg) tablets. |
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| Measure | Description | Time Frame |
|---|---|---|
| Part 1: Area Under The Concentration Versus Time Curve From Time 0 Extrapolated To Infinity (AUC0-inf) Of Single-dose Warfarin Under Multiple Doses Of Danicopan | Up to 168 hours postdose | |
| Part 1: Maximum Observed Concentration (Cmax) Of Single-dose Warfarin Under Multiple Doses Of Danicopan | Up to 168 hours postdose | |
| Part 1: Time To Maximum Observed Concentration (Tmax) Of Single-dose Warfarin Under Multiple Doses Of Danicopan | Up to 168 hours postdose | |
| Part 2: AUC0-inf Of Single-dose Bupropion Under Multiple Doses Of Danicopan | Up to 96 hours postdose | |
| Part 2: Cmax Of Single-dose Bupropion Under Multiple Doses Of Danicopan | Up to 96 hours postdose | |
| Part 2: Tmax Of Single-dose Bupropion Under Multiple Doses Of Danicopan | Up to 96 hours postdose | |
| Part 3: AUC0-inf Of Single-dose EE/NET Under Multiple Doses Of Danicopan | Up to 96 hours postdose | |
| Part 3: Cmax Of Single-dose EE/NET Under Multiple Doses Of Danicopan | Up to 96 hours postdose | |
| Part 3: Tmax Of Single-dose EE/NET Under Multiple Doses Of Danicopan | Up to 96 hours postdose |
| Measure | Description | Time Frame |
|---|---|---|
| Part 1: International Normalized Ratio (INR) Of Single-dose Warfarin Under Multiple Doses Of Danicopan | Blood samples will be collected for prothrombin time/INR determination. | Up to 168 hours postdose |
| Part 1: Number Of Participants With Treatment-emergent Adverse Events (TEAEs) After Multiple Doses Of Danicopan Coadministered With A Single Dose Of Warfarin |
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Inclusion Criteria:
Exclusion Criteria:
Clinically significant laboratory abnormalities.
History of any medical or psychiatric condition or disease that might limit the participant's ability to complete or participate in this clinical study, confound the results of the study, or pose an additional risk to the participant by their participation in the study.
History or presence of drug or alcohol abuse within previous 2 years, current tobacco/nicotine user, or positive for alcohol and/or drug screen at screening or Day -1 of Period 1.
History or presence of clinically significant seizures, head injury, or head trauma.
History of procedures that could alter absorption or excretion of orally administered drugs.
History of meningococcal infection, or a first-degree relative with a history of meningococcal infection.
A history of significant multiple and/or severe allergies or has had an anaphylactic reaction or significant intolerability to prescription or non-prescription drugs.
Body temperature ≥ 38.0°Celsius at screening or prior to first dosing in Period 1 or history of febrile illness, or other evidence of infection, within 14 days prior to first dosing.
Donation of whole blood from 3 months prior to first dosing, or of plasma from 30 days before first dosing, or receipt of blood products within 6 months prior to first dosing.
Participation in any other investigational study drug trial in which receipt of an investigational study drug occurred within 5 half-lives (if known) or 30 days before first dosing, whichever is longer.
Part 1 Only:
History or presence of any of the following, with clinical significance:
Has active severe gingivitis.
Clinically significant illness, clinically significant surgery, including tooth extraction, trauma, or head injury, within 28 days before Day 1 of Period 1.
Participant is employed or actively involved in any circumstance that would place them at increased risk of hemorrhage during the study (for example, contact sports, strenuous or unaccustomed weight lifting, running, bicycling).
Participant has taken large daily doses of vitamin K (> 25 micrograms/daily) and/or has a diet rich in vitamin K 14 days prior to the first dosing.
Part 2 Only:
Any significant finding on the Columbia-suicide severity rating scale.
History or presence of any of the following, with clinical significance:
Part 3 Only:
History or presence of:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Clinical Study Site | Tempe | Arizona | 85283 | United States |
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| ID | Term |
|---|---|
| C000718467 | danicopan |
| D014859 | Warfarin |
| D016642 | Bupropion |
| C484525 | ovcon 35 |
| C014715 | Norinyl |
| ID | Term |
|---|---|
| D015110 | 4-Hydroxycoumarins |
| D003374 | Coumarins |
| D001578 | Benzopyrans |
| D011714 | Pyrans |
| D006573 |
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Part 1, Part 2, and Part 3 could be conducted concurrently or separately.
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| Warfarin | Drug | Warfarin was dosed as 2 x 10 mg and 1 x 5 mg warfarin sodium tablets (Coumadin or generic equivalent). |
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| Bupropion | Drug | Bupropion was dosed as Wellbutrin (or generic equivalent) as 1 x 100 mg tablet. |
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| Ethinyl Estradiol/Norethindrone | Drug | EE/NET (0.035 mg/1 mg) was dosed as Ortho-Novum-1/35 (or generic equivalent) fixed-dose combination tablets. |
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| Day 1 (postdose) through follow-up (14 [+/- 2] days after last study drug administration) |
| Part 2: Number Of Participants With TEAEs After Multiple Doses Of Danicopan Coadministered With A Single Dose Of Bupropion | Day 1 (postdose) through follow-up (14 [+/- 2] days after last study drug administration) |
| Part 3: Number Of Participants With TEAEs After Multiple Doses Of Danicopan Coadministered With A Single Dose Of EE/NET | Day 1 (postdose) through follow-up (14 [+/- 2] days after last study drug administration) |
| Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D011427 | Propiophenones |
| D007659 | Ketones |
| D009930 | Organic Chemicals |