Clinical trial NCT06071442: Potential Drug Interaction Study Between Vemircopan and Rosuvastatin, Metformin, Levonorgestrel/Ethinyl Estradiol-containing Oral Contraceptives, and Carbamazepine
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Participants
Keywords: Drug-drug interaction
Pharmacokinetic
Lead sponsor: Alexion Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2023-10-06
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Part 1: Maximum observed plasma (peak) concentration (Cmax) of Metformin
timeFrame: Up to 48 hours post-dose
measure: Part 1: AUC from time zero to the last quantifiable concentration (AUCt) of Metformin
timeFrame: Up to 48 hours post-dose
measure: Part 1: AUC from time zero extrapolated to infinity (AUC∞) of Metformin
timeFrame: Up to 48 hours post-dose
measure: Part 1: Cmax of Rosuvastatin
timeFrame: Up to 96 hours post-dose
measure: Part 1: AUCt of Rosuvastatin
timeFrame: Up to 96 hours post-dose
measure: Part 1: AUC∞ of Rosuvastatin
timeFrame: Up to 96 hours post-dose
measure: Part 2: Cmax of LNG
timeFrame: Up to 120 hours post-dose
measure: Part 2: AUCt of LNG
timeFrame: Up to 120 hours post-dose
measure: Part 2: AUC∞ of LNG
timeFrame: Up to 120 hours post-dose
measure: Part 2: Cmax of EE
timeFrame: Up to 120 hours post-dose
measure: Part 2: AUCt of EE
timeFrame: Up to 120 hours post-dose
measure: Part 2: AUC∞ of EE
timeFrame: Up to 120 hours post-dose
measure: Part 3: Cmax of Vemircopan
timeFrame: Up to 72 hours post-dose
measure: Part 3: AUCt of Vemircopan
timeFrame: Up to 72 hours post-dose
measure: Part 3: AUC∞ of Vemircopan
timeFrame: Up to 72 hours post-dose
Secondary outcomes:
measure: Part 1: Number of participants with Treatment Emergent Adverse Events
timeFrame: From Screening (Day -28 to Day -2) up to follow-up Visit or early discontinuation visit (approximately 57 days)
measure: Part 2: Number of participants with Treatment Emergent Adverse Events
timeFrame: From Screening (Day -28 to Day -2) up to follow-up Visit or early discontinuation visit (approximately 54 days)
measure: Part 3: Number of participants with Treatment Emergent Adverse Events
timeFrame: From Screening (Day -28 to Day -2) up to follow-up Visit or early discontinuation visit (approximately 63 days)
measure: Part 1: Time corresponding to the occurrence of Cmax (tmax) of Metformin
timeFrame: Up to 48 hours post-dose
measure: Part 1: Apparent terminal elimination half-life (t½) of Metformin
timeFrame: Up to 48 hours post-dose
measure: Part 1: Terminal elimination rate constant (λz) of Metformin
timeFrame: Up to 48 hours post-dose
measure: Part 1: Volume of distribution (apparent) following extravascular administration (Vd/F) of Metformin
timeFrame: Up to 48 hours post-dose
measure: Part 1: Apparent total body clearance of drug from plasma after extravascular administration (CL/F) of Metformin
timeFrame: Up to 48 hours post-dose
measure: Part 1: tmax of Rosuvastatin
timeFrame: Up to 96 hours post-dose
measure: Part 1: t½ of Rosuvastatin
timeFrame: Up to 96 hours post-dose
measure: Part 1: λz of Rosuvastatin
timeFrame: Up to 96 hours post-dose
measure: Part 1: Vd/F of Rosuvastatin
timeFrame: Up to 96 hours post-dose
measure: Part 1: CL/F of Rosuvastatin
timeFrame: Up to 96 hours post-dose
measure: Part 1: Cmax of Vemircopan
timeFrame: Period 2: Days 4, 5 and 8
measure: Part 1: AUC during a dosing interval at steady state (AUCtau) of Vemircopan
timeFrame: Period 2: Days 4, 5 and 8
measure: Part 1: tmax of Vemircopan
timeFrame: Period 2: Days 4, 5 and 8
measure: Part 1: Predose concentration prior to morning dose (Ctrough) of Vemircopan
timeFrame: Period 2: Days 3, 4, 5 and 8
measure: Part 2: tmax of LNG
timeFrame: Up to 120 hours post-dose
measure: Part 2: t½ of LNG
timeFrame: Up to 120 hours post-dose
measure: Part 2: λz of LNG
timeFrame: Up to 120 hours post-dose
measure: Part 2: Vd/F of LNG
timeFrame: Up to 120 hours post-dose
measure: Part 2: CL/F of LNG
timeFrame: Up to 120 hours post-dose
measure: Part 2: tmax of EE
timeFrame: Up to 120 hours post-dose
measure: Part 2: t½ of EE
timeFrame: Up to 120 hours post-dose
measure: Part 2: λz of EE
timeFrame: Up to 120 hours post-dose
measure: Part 2: Vd/F of EE
timeFrame: Up to 120 hours post-dose
measure: Part 2: CL/F of EE
timeFrame: Up to 120 hours post-dose
measure: Part 2: Cmax of Vemircopan
timeFrame: Period 2: Days 4, and 5
measure: Part 2: AUCtau of Vemircopan
timeFrame: Period 2: Days 4, and 5
measure: Part 2: tmax of Vemircopan
timeFrame: Period 2: Days 4, and 5
measure: Part 2: Ctrough of Vemircopan
timeFrame: Period 2: Days 3, 4, and 5
measure: Part 3: tmax of Vemircopan
timeFrame: Up to 72 hours post-dose
measure: Part 3: t½ of Vemircopan
timeFrame: Up to 72 hours post-dose
measure: Part 3: λz of Vemircopan
timeFrame: Up to 72 hours post-dose
measure: Part 3: Vd/F of Vemircopan
timeFrame: Up to 72 hours post-dose
measure: Part 3: CL/F of Vemircopan
timeFrame: Up to 96 hours post-dose
measure: Part 3: Cmax of Carbamazepine
timeFrame: Period 2: Days 4, 18 and 19
measure: Part 3: AUCtau of Carbamazepine
timeFrame: Period 2: Days 4, 18 and 19
measure: Part 3: tmax of Carbamazepine
timeFrame: Period 2: Days 4, 18 and 19
measure: Part 3: Ctrough of Carbamazepine
timeFrame: Period 2: Days 18 and 19
Other outcomes:
Locations:
city: Brooklyn
country: United States
facility: Research Site
state: Maryland
Study officials:
References: