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

Alexion Pharmaceuticals, Inc.60 enrolled

Overview

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.

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

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Healthy Participants

Interventions

VemircopanDRUG

Participants will receive oral tablets of Vemircopan.

RosuvastatinDRUG

Participants will receive oral coated tablets of Rosuvastatin.

MetforminDRUG

Participants will receive oral film-coated tablets of Metformin.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 55 YearsHealthy volunteers:

Medical Language ↔ Plain English

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.

Locations (1)

Research Site

Brooklyn, Maryland, United States

Outcomes

Primary Outcomes

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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: Up to 96 hours post-dose

Data from ClinicalTrials.gov

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Secondary Outcomes

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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: Up to 96 hours post-dose

Part 1: Cmax of Vemircopan

Cmax of vermircopan after multiple twice daily doses will be assessed.

Time frame: 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.

Time frame: Period 2: Days 4, 5 and 8

Part 1: tmax of Vemircopan

tmax of vermircopan after multiple twice daily doses will be assessed.

Time frame: 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.

Time frame: 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.