Potential Drug Interaction Study Between Vemircopan and Rosuvastatin, Metformin, Levonorgestrel/Ethinyl Estradiol-containing Oral Contraceptives, and Carbamazepine
- Conditions
- Healthy Participants
- Interventions
- Registration Number
- NCT06071442
- Lead Sponsor
- Alexion Pharmaceuticals, Inc.
- Brief Summary
This study will investigate the potential drug interactions between vemircopan and metformin, rosuvastatin, levonorgestrel/ ethinyl estradiol (LNG/EE)-containing oral contraceptive(s) (OCs), and carbamazepine in healthy participants.
- Detailed Description
This a 3-part drug-drug interaction (DDI) study. Part 1 - Potential Drug-drug Interaction Between Vemircopan, Metformin, and Rosuvastatin, Part 2 - Potential Drug-drug Interaction Between Vemircopan and LNG/EE-Containing OCs (Female Participants Only) Part 3 - Potential Drug-drug Interaction Between Vemircopan and Carbamazepine
All the 3 parts of the study includes:
* Screening Period: 27 days (Day -28 through Day -2)
* Two Treatment Periods:
* Part 1: Treatment Period 1 (Day -1 through Day 8) and Treatment Period 2 (Day 1 through Day 12)
* Part 2: Treatment Period 1 (Day -1 through Day 7) and Treatment Period 2 (Day 1 through Day 10)
* Part 3: Treatment Period 1 (Day -1 through Day 4) and Treatment Period 2 (Day 1 through Day 22)
* Follow-up/Early Discontinuation Visit: 7 (± 2) days following the last dose of study intervention
Up to 20 participants will be enrolled per study part. Participants will be enrolled in only one study part and will not be allowed to participate in more than 1 study part.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 60
- Participants who are medically healthy with no clinically significant or relevant abnormalities as determined by medical history, physical or neurological examination, vital signs, 12-lead ECG, screening clinical laboratory profiles (hematology, biochemistry, coagulation, and urinalysis), as deemed by the Investigator or designee.
- Body weight of at minimum 50 kg and body mass index (BMI) within the range 18 to 32 kg/m^2 (inclusive) at the Screening.
- Male and female participants should adhere to the protocol defined contraceptive methods.
- History or presence of medical (eg, cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrinological, hematological, neurological or other disorders) or psychiatric conditions or diseases.
- History of clinically significant hypersensitivity or idiosyncratic reaction to the study drugs or related compounds.
- History of drug or alcohol abuse within 2 years prior to first dosing
- Current tobacco users or smokers (defined as any tobacco or nicotine-containing product use within 3 months prior to first dosing).
- Donation of whole blood from 3 months prior to first dose administration, or of plasma from 30 days before first dose administration.
- Female participants who have a positive pregnancy test at Screening or Day -1, or who are lactating.
- Positive drugs of abuse, cotinine, or alcohol screen at Screening or Day -1.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Part 1: Vemircopan, Metformin and Rosuvastatin Rosuvastatin Participants will receive Vemircopan, Metformin and Rosuvastatin in a fixed sequence over 2 periods. Period 1 (8 days): Participants will receive a single dose of metformin on day 1 and a single dose of rosuvastatin on day 4. Period 2 (12 days): Participants will receive vemircopan twice daily from day 1 to day 11. On day 5, participants will receive metformin co-administered with vemircopan. On day 8, participants will receive rosuvastatin co-administered with vemircopan. There will be a washout period of at least 4 days between the dose of rosuvastatin in Period 1 and the first dose of vemircopan in Period 2. Part 2: Vemircopan and LNG/EE-Containing OCs Levonorgestrel / Ethinyl Estradiol Participants will receive Vemircopan and LNG/EE-Containing OCs in a fixed sequence over 2 periods. Period 1 (7 days): Participants will receive a single dose of OC, consisting of LNG and EE on day 1. Period 2 (10 days): Participants will receive multiple doses of vemircopan from day 1 to day 9. On day 5, participants will receive a single dose of OC co-administered with vemircopan. There will be a washout period of at least 7 days between the dose of OC in Period 1 and the first dose of vemircopan in Period 2. Part 1: Vemircopan, Metformin and Rosuvastatin Metformin Participants will receive Vemircopan, Metformin and Rosuvastatin in a fixed sequence over 2 periods. Period 1 (8 days): Participants will receive a single dose of metformin on day 1 and a single dose of rosuvastatin on day 4. Period 2 (12 days): Participants will receive vemircopan twice daily from day 1 to day 11. On day 5, participants will receive metformin co-administered with vemircopan. On day 8, participants will receive rosuvastatin co-administered with vemircopan. There will be a washout period of at least 4 days between the dose of rosuvastatin in Period 1 and the first dose of vemircopan in Period 2. Part 3: Vemircopan and Carbamazepine Carbamazepine Participants will receive Vemircopan and Carbemazepine in a fixed sequence over 2 periods. Period 1 (4 days): Participants will receive a single oral dose of vemircopan on day 1. Period 2 (22 days): Participants will receive carbemazepine twice daily from day 1 to day 21. On day 19, participants will receive a single oral dose of vemircopan co-administered with carbamazepine. There will be a washout period of at least 4 days between the dose of vemircopan in Period 1 and the first dose of carbamazepine in Period 2. Part 1: Vemircopan, Metformin and Rosuvastatin Vemircopan Participants will receive Vemircopan, Metformin and Rosuvastatin in a fixed sequence over 2 periods. Period 1 (8 days): Participants will receive a single dose of metformin on day 1 and a single dose of rosuvastatin on day 4. Period 2 (12 days): Participants will receive vemircopan twice daily from day 1 to day 11. On day 5, participants will receive metformin co-administered with vemircopan. On day 8, participants will receive rosuvastatin co-administered with vemircopan. There will be a washout period of at least 4 days between the dose of rosuvastatin in Period 1 and the first dose of vemircopan in Period 2. Part 2: Vemircopan and LNG/EE-Containing OCs Vemircopan Participants will receive Vemircopan and LNG/EE-Containing OCs in a fixed sequence over 2 periods. Period 1 (7 days): Participants will receive a single dose of OC, consisting of LNG and EE on day 1. Period 2 (10 days): Participants will receive multiple doses of vemircopan from day 1 to day 9. On day 5, participants will receive a single dose of OC co-administered with vemircopan. There will be a washout period of at least 7 days between the dose of OC in Period 1 and the first dose of vemircopan in Period 2. Part 3: Vemircopan and Carbamazepine Vemircopan Participants will receive Vemircopan and Carbemazepine in a fixed sequence over 2 periods. Period 1 (4 days): Participants will receive a single oral dose of vemircopan on day 1. Period 2 (22 days): Participants will receive carbemazepine twice daily from day 1 to day 21. On day 19, participants will receive a single oral dose of vemircopan co-administered with carbamazepine. There will be a washout period of at least 4 days between the dose of vemircopan in Period 1 and the first dose of carbamazepine in Period 2.
- Primary Outcome Measures
Name Time Method Part 1: Cmax of Rosuvastatin Up to 96 hours post-dose Cmax for single-dose rosuvastatin without and with co-administration with vemircopan will be assessed to determine the effect of multiple doses of vemircopan on the single-dose PK of rosuvastatin.
Part 1: Maximum observed plasma (peak) concentration (Cmax) of Metformin Up to 48 hours post-dose Cmax for single-dose metformin without and with co-administration with vemircopan will be assessed to determine the effect of multiple doses of vemircopan on the single-dose PK of metformin.
Part 1: AUC from time zero to the last quantifiable concentration (AUCt) of Metformin Up to 48 hours post-dose AUCt for single-dose metformin without and with co-administration with vemircopan will be assessed to determine the effect of multiple doses of vemircopan on the single-dose PK of metformin.
Part 2: Cmax of EE Up to 120 hours post-dose Cmax for single-dose EE without and with co-administration with vemircopan will be assessed to determine the effect of multiple doses of vemircopan on the single-dose PK of EE.
Part 2: AUC∞ of EE Up to 120 hours post-dose Cmax for single-dose EE without and with co-administration with vemircopan will be assessed to determine the effect of multiple doses of vemircopan on the single-dose PK of EE.
Part 2: AUCt of EE Up to 120 hours post-dose AUCt for single-dose EE without and with co-administration with vemircopan will be assessed to determine the effect of multiple doses of vemircopan on the single-dose PK of EE.
Part 3: AUC∞ of Vemircopan Up to 72 hours post-dose Cmax for single-dose vemircopan without and with co-administration with carbamazepine will be assessed to determine the effect of multiple doses of carbamazepine on the single-dose PK of vemircopan.
Part 1: AUC from time zero extrapolated to infinity (AUC∞) of Metformin Up to 48 hours post-dose Cmax for single-dose metformin without and with co-administration with vemircopan will be assessed to determine the effect of multiple doses of vemircopan on the single-dose PK of metformin.
Part 1: AUC∞ of Rosuvastatin Up to 96 hours post-dose Cmax for single-dose rosuvastatin without and with co-administration with vemircopan will be assessed to determine the effect of multiple doses of vemircopan on the single-dose PK of rosuvastatin.
Part 2: AUCt of LNG Up to 120 hours post-dose AUCt for single-dose LNG without and with co-administration with vemircopan will be assessed to determine the effect of multiple doses of vemircopan on the single-dose PK of LNG.
Part 3: AUCt of Vemircopan Up to 72 hours post-dose AUCt for single-dose vemircopan without and with co-administration with carbamazepine will be assessed to determine the effect of multiple doses of carbamazepine on the single-dose PK of vemircopan.
Part 1: AUCt of Rosuvastatin Up to 96 hours post-dose AUCt for single-dose rosuvastatin without and with co-administration with vemircopan will be assessed to determine the effect of multiple doses of vemircopan on the single-dose PK of rosuvastatin.
Part 2: Cmax of LNG Up to 120 hours post-dose Cmax for single-dose LNG without and with co-administration with vemircopan will be assessed to determine the effect of multiple doses of vemircopan on the single-dose PK of LNG.
Part 2: AUC∞ of LNG Up to 120 hours post-dose Cmax for single-dose LNG without and with co-administration with vemircopan will be assessed to determine the effect of multiple doses of vemircopan on the single-dose PK of LNG.
Part 3: Cmax of Vemircopan Up to 72 hours post-dose Cmax for single-dose vemircopan without and with co-administration with carbamazepine will be assessed to determine the effect of multiple doses of carbamazepine on the single-dose PK of vemircopan.
- Secondary Outcome Measures
Name Time Method Part 1: Time corresponding to the occurrence of Cmax (tmax) of Metformin Up to 48 hours post-dose tmax for single-dose metformin without and with co-administration with vemircopan will be assessed to determine the effect of multiple doses of vemircopan on metformin.
Part 1: CL/F of Rosuvastatin Up to 96 hours post-dose CL/F for single-dose rosuvastatin without and with co-administration with vemircopan will be assessed to determine the effect of multiple doses of vemircopan on rosuvastatin.
Part 3: Number of participants with Treatment Emergent Adverse Events From Screening (Day -28 to Day -2) up to follow-up Visit or early discontinuation visit (approximately 63 days) The safety and tolerability of multiple doses of vemircopan when co-administered with multiple doses of carbamazepine will be assessed.
Part 1: Apparent terminal elimination half-life (t½) of Metformin Up to 48 hours post-dose t½ for single-dose metformin without and with co-administration with vemircopan will be assessed to determine the effect of multiple doses of vemircopan on metformin.
Part 2: Number of participants with Treatment Emergent Adverse Events From Screening (Day -28 to Day -2) up to follow-up Visit or early discontinuation visit (approximately 54 days) The safety and tolerability of multiple doses of vemircopan when co-administered with a single dose of an oral contraceptive containing both LNG and EE will be assessed.
Part 1: Number of participants with Treatment Emergent Adverse Events From Screening (Day -28 to Day -2) up to follow-up Visit or early discontinuation visit (approximately 57 days) The safety and tolerability of multiple doses of vemircopan when co-administered with a single dose of metformin, and multiple doses of vemircopan when co-administered with a single dose of rosuvastatin will be assessed.
Part 1: t½ of Rosuvastatin Up to 96 hours post-dose t½ for single-dose rosuvastatin without and with co-administration with vemircopan will be assessed to determine the effect of multiple doses of vemircopan on rosuvastatin.
Part 1: λz of Rosuvastatin Up to 96 hours post-dose λz for single-dose rosuvastatin without and with co-administration with vemircopan will be assessed to determine the effect of multiple doses of vemircopan on rosuvastatin.
Part 1: AUC during a dosing interval at steady state (AUCtau) of Vemircopan Period 2: Days 4, 5 and 8 AUCtau of vermircopan after multiple twice daily doses will be assessed.
Part 1: Terminal elimination rate constant (λz) of Metformin Up to 48 hours post-dose λz for single-dose metformin without and with co-administration with vemircopan will be assessed to determine the effect of multiple doses of vemircopan on metformin.
Part 1: Volume of distribution (apparent) following extravascular administration (Vd/F) of Metformin Up to 48 hours post-dose Vd/F for single-dose metformin without and with co-administration with vemircopan will be assessed to determine the effect of multiple doses of vemircopan on metformin.
Part 1: Apparent total body clearance of drug from plasma after extravascular administration (CL/F) of Metformin Up to 48 hours post-dose CL/F for single-dose metformin without and with co-administration with vemircopan will be assessed to determine the effect of multiple doses of vemircopan on metformin.
Part 1: tmax of Rosuvastatin Up to 96 hours post-dose tmax for single-dose rosuvastatin without and with co-administration with vemircopan will be assessed to determine the effect of multiple doses of vemircopan on rosuvastatin.
Part 1: Predose concentration prior to morning dose (Ctrough) of Vemircopan Period 2: Days 3, 4, 5 and 8 Ctrough of vermircopan after multiple twice daily doses will be assessed.
Part 2: λz of LNG Up to 120 hours post-dose λz for single-dose LNG without and with co-administration with vemircopan will be assessed to determine the effect of multiple doses of vemircopan on LNG.
Part 2: Vd/F of LNG Up to 120 hours post-dose Vd/F for single-dose LNG without and with co-administration with vemircopan will be assessed to determine the effect of multiple doses of vemircopan on LNG.
Part 2: CL/F of LNG Up to 120 hours post-dose CL/F for single-dose LNG without and with co-administration with vemircopan will be assessed to determine the effect of multiple doses of vemircopan on LNG.
Part 2: tmax of EE Up to 120 hours post-dose tmax for single-dose EE without and with co-administration with vemircopan will be assessed to determine the effect of multiple doses of vemircopan on EE.
Part 2: λz of EE Up to 120 hours post-dose λz for single-dose EE without and with co-administration with vemircopan will be assessed to determine the effect of multiple doses of vemircopan on EE.
Part 2: Vd/F of EE Up to 120 hours post-dose Vd/F for single-dose EE without and with co-administration with vemircopan will be assessed to determine the effect of multiple doses of vemircopan on EE.
Part 1: Vd/F of Rosuvastatin Up to 96 hours post-dose Vd/F for single-dose rosuvastatin without and with co-administration with vemircopan will be assessed to determine the effect of multiple doses of vemircopan on rosuvastatin.
Part 1: Cmax of Vemircopan Period 2: Days 4, 5 and 8 Cmax of vermircopan after multiple twice daily doses will be assessed.
Part 1: tmax of Vemircopan Period 2: Days 4, 5 and 8 tmax of vermircopan after multiple twice daily doses will be assessed.
Part 2: t½ of LNG Up to 120 hours post-dose t½ for single-dose LNG without and with co-administration with vemircopan will be assessed to determine the effect of multiple doses of vemircopan on LNG.
Part 2: tmax of LNG Up to 120 hours post-dose tmax for single-dose LNG without and with co-administration with vemircopan will be assessed to determine the effect of multiple doses of vemircopan on LNG.
Part 2: t½ of EE Up to 120 hours post-dose t½ for single-dose EE without and with co-administration with vemircopan will be assessed to determine the effect of multiple doses of vemircopan on EE.
Part 2: AUCtau of Vemircopan Period 2: Days 4, and 5 AUCtau of vermircopan after multiple twice daily doses will be assessed.
Part 3: tmax of Vemircopan Up to 72 hours post-dose tmax for single-dose vemircopan without and with co-administration with carbamazepine will be assessed to determine the effect of multiple doses of carbamazepine on vemircopan.
Part 2: CL/F of EE Up to 120 hours post-dose CL/F for single-dose EE without and with co-administration with vemircopan will be assessed to determine the effect of multiple doses of vemircopan on EE.
Part 2: Cmax of Vemircopan Period 2: Days 4, and 5 Cmax of vermircopan after multiple twice daily doses will be assessed.
Part 3: λz of Vemircopan Up to 72 hours post-dose λz for single-dose vemircopan without and with co-administration with carbamazepine will be assessed to determine the effect of multiple doses of carbamazepine on vemircopan.
Part 3: Cmax of Carbamazepine Period 2: Days 4, 18 and 19 Cmax of carbamazepine after multiple twice daily doses will be assessed.
Part 3: AUCtau of Carbamazepine Period 2: Days 4, 18 and 19 AUCtau of carbamazepine after multiple twice daily doses will be assessed.
Part 2: tmax of Vemircopan Period 2: Days 4, and 5 tmax of vermircopan after multiple twice daily doses will be assessed.
Part 2: Ctrough of Vemircopan Period 2: Days 3, 4, and 5 Ctrough of vermircopan after multiple twice daily doses will be assessed.
Part 3: t½ of Vemircopan Up to 72 hours post-dose t½ for single-dose vemircopan without and with co-administration with carbamazepine will be assessed to determine the effect of multiple doses of carbamazepine on vemircopan.
Part 3: Vd/F of Vemircopan Up to 72 hours post-dose Vd/F for single-dose vemircopan without and with co-administration with carbamazepine will be assessed to determine the effect of multiple doses of carbamazepine on vemircopan.
Part 3: CL/F of Vemircopan Up to 96 hours post-dose CL/F for single-dose vemircopan without and with co-administration with carbamazepine will be assessed to determine the effect of multiple doses of carbamazepine on vemircopan.
Part 3: tmax of Carbamazepine Period 2: Days 4, 18 and 19 tmax of carbamazepine after multiple twice daily doses will be assessed.
Part 3: Ctrough of Carbamazepine Period 2: Days 18 and 19 Ctrough of carbamazepine after multiple twice daily doses will be assessed.
Trial Locations
- Locations (1)
Research Site
🇺🇸Brooklyn, Maryland, United States