Potential Drug Interaction Study Between Vemircopan and Rosuvastatin, Metformin, Levonorgestrel/Ethinyl Estradiol-containing Oral Contraceptives, and Carbamazepine

Study Overview
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Brief Summary
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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
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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.

Official Title
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A Three-Part Phase 1 Study to Evaluate the Potential Drug-Drug Interactions Between Vemircopan and Rosuvastatin, Metformin, Levonorgestrel-Ethinyl Estradiol-Containing Oral Contraceptives, and Carbamazepine in Healthy Adult Participants

Conditions
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Healthy Participants

Intervention / Treatment
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* Drug: Vemircopan
* Drug: Rosuvastatin
* Drug: Metformin
* Drug: Levonorgestrel / Ethinyl Estradiol
* Drug: Carbamazepine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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. Exclusion Criteria: 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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part 1: Vemircopan, Metformin and Rosuvastatin<br>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. | Drug: Vemircopan<br>* Participants will receive oral tablets of Vemircopan.<br>* Other names: ALXN2050;Drug: Rosuvastatin<br>* Participants will receive oral coated tablets of Rosuvastatin.<br>Drug: Metformin<br>* Participants will receive oral film-coated tablets of Metformin.<br>|
| Experimental: Part 2: Vemircopan and LNG/EE-Containing OCs<br>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. | Drug: Vemircopan<br>* Participants will receive oral tablets of Vemircopan.<br>* Other names: ALXN2050;Drug: Levonorgestrel / Ethinyl Estradiol<br>* Participants will receive oral tablets of Levonorgestrel/ Ethinyl Estradiol.<br>* Other names: SIMPESSE;|
| Experimental: Part 3: Vemircopan and Carbamazepine<br>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. | Drug: Vemircopan<br>* Participants will receive oral tablets of Vemircopan.<br>* Other names: ALXN2050;Drug: Carbamazepine<br>* Participants will receive oral chewable tablets of Carbamazepine.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part 1: Maximum observed plasma (peak) concentration (Cmax) of Metformin | 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. | Up to 48 hours post-dose | 
| Part 1: AUC from time zero to the last quantifiable concentration (AUCt) of Metformin | 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. | Up to 48 hours post-dose | 
| Part 1: AUC from time zero extrapolated to infinity (AUC∞) of Metformin | 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. | Up to 48 hours post-dose | 
| Part 1: Cmax of Rosuvastatin | 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. | Up to 96 hours post-dose | 
| Part 1: AUCt of Rosuvastatin | 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. | Up to 96 hours post-dose | 
| Part 1: AUC∞ of Rosuvastatin | 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. | Up to 96 hours post-dose | 
| Part 2: Cmax of LNG | 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. | Up to 120 hours post-dose | 
| Part 2: AUCt of LNG | 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. | Up to 120 hours post-dose | 
| Part 2: AUC∞ of LNG | 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. | Up to 120 hours post-dose | 
| Part 2: Cmax of EE | 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. | Up to 120 hours post-dose | 
| Part 2: AUCt of EE | 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. | Up to 120 hours post-dose | 
| Part 2: AUC∞ of EE | 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. | Up to 120 hours post-dose | 
| Part 3: Cmax of Vemircopan | 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. | Up to 72 hours post-dose | 
| Part 3: AUCt of Vemircopan | 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. | Up to 72 hours post-dose | 
| Part 3: AUC∞ of Vemircopan | 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. | Up to 72 hours post-dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part 1: Number of participants with Treatment Emergent Adverse Events | 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. | From Screening (Day -28 to Day -2) up to follow-up Visit or early discontinuation visit (approximately 57 days) | 
| Part 2: Number of participants with Treatment Emergent Adverse Events | 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. | From Screening (Day -28 to Day -2) up to follow-up Visit or early discontinuation visit (approximately 54 days) | 
| Part 3: Number of participants with Treatment Emergent Adverse Events | The safety and tolerability of multiple doses of vemircopan when co-administered with multiple doses of carbamazepine will be assessed. | From Screening (Day -28 to Day -2) up to follow-up Visit or early discontinuation visit (approximately 63 days) | 
| Part 1: Time corresponding to the occurrence of Cmax (tmax) of Metformin | 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. | Up to 48 hours post-dose | 
| Part 1: Apparent terminal elimination half-life (t½) of Metformin | 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. | Up to 48 hours post-dose | 
| Part 1: Terminal elimination rate constant (λz) of Metformin | 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. | Up to 48 hours post-dose | 
| Part 1: Volume of distribution (apparent) following extravascular administration (Vd/F) of Metformin | 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. | Up to 48 hours post-dose | 
| Part 1: Apparent total body clearance of drug from plasma after extravascular administration (CL/F) of Metformin | 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. | Up to 48 hours post-dose | 
| Part 1: tmax of Rosuvastatin | 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. | Up to 96 hours post-dose | 
| Part 1: t½ of Rosuvastatin | 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. | Up to 96 hours post-dose | 
| Part 1: λz of Rosuvastatin | 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. | Up to 96 hours post-dose | 
| Part 1: Vd/F of Rosuvastatin | 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. | Up to 96 hours post-dose | 
| Part 1: CL/F of Rosuvastatin | 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. | Up to 96 hours post-dose | 
| Part 1: Cmax of Vemircopan | Cmax of vermircopan after multiple twice daily doses will be assessed. | Period 2: Days 4, 5 and 8 | 
| Part 1: AUC during a dosing interval at steady state (AUCtau) of Vemircopan | AUCtau of vermircopan after multiple twice daily doses will be assessed. | Period 2: Days 4, 5 and 8 | 
| Part 1: tmax of Vemircopan | tmax of vermircopan after multiple twice daily doses will be assessed. | Period 2: Days 4, 5 and 8 | 
| Part 1: Predose concentration prior to morning dose (Ctrough) of Vemircopan | Ctrough of vermircopan after multiple twice daily doses will be assessed. | Period 2: Days 3, 4, 5 and 8 | 
| Part 2: tmax of LNG | 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. | Up to 120 hours post-dose | 
| Part 2: t½ of LNG | 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. | Up to 120 hours post-dose | 
| Part 2: λz of LNG | 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. | Up to 120 hours post-dose | 
| Part 2: Vd/F of LNG | 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. | Up to 120 hours post-dose | 
| Part 2: CL/F of LNG | 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. | Up to 120 hours post-dose | 
| Part 2: tmax of EE | 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. | Up to 120 hours post-dose | 
| Part 2: t½ of EE | 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. | Up to 120 hours post-dose | 
| Part 2: λz of EE | 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. | Up to 120 hours post-dose | 
| Part 2: Vd/F of EE | 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. | Up to 120 hours post-dose | 
| Part 2: CL/F of EE | 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. | Up to 120 hours post-dose | 
| Part 2: Cmax of Vemircopan | Cmax of vermircopan after multiple twice daily doses will be assessed. | Period 2: Days 4, and 5 | 
| Part 2: AUCtau of Vemircopan | AUCtau of vermircopan after multiple twice daily doses will be assessed. | Period 2: Days 4, and 5 | 
| Part 2: tmax of Vemircopan | tmax of vermircopan after multiple twice daily doses will be assessed. | Period 2: Days 4, and 5 | 
| Part 2: Ctrough of Vemircopan | Ctrough of vermircopan after multiple twice daily doses will be assessed. | Period 2: Days 3, 4, and 5 | 
| Part 3: tmax of Vemircopan | 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. | Up to 72 hours post-dose | 
| Part 3: t½ of Vemircopan | 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. | Up to 72 hours post-dose | 
| Part 3: λz of Vemircopan | 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. | Up to 72 hours post-dose | 
| Part 3: Vd/F of Vemircopan | 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. | Up to 72 hours post-dose | 
| Part 3: CL/F of Vemircopan | 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. | Up to 96 hours post-dose | 
| Part 3: Cmax of Carbamazepine | Cmax of carbamazepine after multiple twice daily doses will be assessed. | Period 2: Days 4, 18 and 19 | 
| Part 3: AUCtau of Carbamazepine | AUCtau of carbamazepine after multiple twice daily doses will be assessed. | Period 2: Days 4, 18 and 19 | 
| Part 3: tmax of Carbamazepine | tmax of carbamazepine after multiple twice daily doses will be assessed. | Period 2: Days 4, 18 and 19 | 
| Part 3: Ctrough of Carbamazepine | Ctrough of carbamazepine after multiple twice daily doses will be assessed. | Period 2: Days 18 and 19 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Drug-drug interaction, Pharmacokinetic