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

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

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.

Study Overview

• Status: Completed
• Conditions: Healthy Participants
• Intervention / Treatment: Drug: Vemircopan; Drug: Rosuvastatin; Drug: Metformin; Drug: Levonorgestrel / Ethinyl Estradiol; Drug: Carbamazepine

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.

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Brooklyn, Maryland, United States, 21225
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Alexion Pharmaceuticals, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): January 17, 2024
• Primary Completion (Actual): April 12, 2024
• Study Completion (Actual): April 12, 2024

Study Registration Dates

• First Submitted: October 2, 2023
• First Submitted That Met QC Criteria: October 2, 2023
• First Posted (Actual): October 6, 2023

Study Record Updates

• Last Update Posted (Actual): August 12, 2025
• Last Update Submitted That Met QC Criteria: August 11, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Keywords: Pharmacokinetic; Drug-drug interaction
• Additional Relevant MeSH Terms: Contraceptive Agents, Hormonal; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Hypoglycemic Agents; Peripheral Nervous System Agents; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Enzyme Inhibitors; Reproductive Control Agents; Antimetabolites; Central Nervous System Depressants; Sensory System Agents; Analgesics, Non-Narcotic; Analgesics; Sodium Channel Blockers; Membrane Transport Modulators; Tranquilizing Agents; Psychotropic Drugs; Anticonvulsants; Antimanic Agents; Contraceptive Agents, Female; Contraceptive Agents; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Estrogens; Cytochrome P-450 Enzyme Inducers; Cytochrome P-450 CYP3A Inducers; Contraceptives, Oral; Contraceptives, Oral, Hormonal; Contraceptives, Oral, Synthetic; Rosuvastatin Calcium; Metformin; Estradiol; Levonorgestrel; Carbamazepine; Ethinyl Estradiol
• Other Study ID Numbers: D7841C00012; ALXN2050-HV-111 (Other Identifier: Alexion)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal Vivli.org. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

"Yes", indicates that AZ are accepting requests for IPD, but this does not mean all requests will be approved.

• IPD Sharing Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA/PhRMA Data-Sharing Principles. For details of our timelines, please refer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• IPD Sharing Access Criteria: When a request has been approved AstraZeneca will provide access to the anonymized individual patient-level data via secure research environment Vivli.org. A Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No