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

Healthy Participants Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT06071442
• Other study ID #: D7841C00012
• Status: Completed
• Phase: Phase 1
• Start date: January 17, 2024
• Est. completion date: April 12, 2024

Study information

• Verified date: May 2024
• Source: Alexion Pharmaceuticals, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 60
• Est. completion date: April 12, 2024
• Est. primary completion date: April 12, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

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.

Related Conditions & MeSH terms

• Healthy Participants

Intervention

Drug:
• Vemircopan
Participants will receive oral tablets of Vemircopan.
• Rosuvastatin
Participants will receive oral coated tablets of Rosuvastatin.
• Metformin
Participants will receive oral film-coated tablets of Metformin.
• Levonorgestrel / Ethinyl Estradiol
Participants will receive oral tablets of Levonorgestrel/ Ethinyl Estradiol.
• Carbamazepine
Participants will receive oral chewable tablets of Carbamazepine.

Locations

Country	Name	City	State
United States	Research Site	Brooklyn	Maryland

Sponsors (1)

Lead Sponsor	Collaborator
Alexion Pharmaceuticals, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	Part 1: AUC from time zero extrapolated to infinity (AUC8) 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
Primary	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
Primary	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
Primary	Part 1: AUC8 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
Primary	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
Primary	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
Primary	Part 2: AUC8 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
Primary	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
Primary	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
Primary	Part 2: AUC8 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
Primary	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
Primary	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
Primary	Part 3: AUC8 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	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)
Secondary	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)
Secondary	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)
Secondary	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
Secondary	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
Secondary	Part 1: Terminal elimination rate constant (?z) of Metformin	?z 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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Part 1: ?z of Rosuvastatin	?z 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
Secondary	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
Secondary	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
Secondary	Part 1: Cmax of Vemircopan	Cmax of vermircopan after multiple twice daily doses will be assessed.	Period 2: Days 4, 5 and 8
Secondary	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
Secondary	Part 1: tmax of Vemircopan	tmax of vermircopan after multiple twice daily doses will be assessed.	Period 2: Days 4, 5 and 8
Secondary	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
Secondary	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
Secondary	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
Secondary	Part 2: ?z of LNG	?z 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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Part 2: ?z of EE	?z 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
Secondary	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
Secondary	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
Secondary	Part 2: Cmax of Vemircopan	Cmax of vermircopan after multiple twice daily doses will be assessed.	Period 2: Days 4, and 5
Secondary	Part 2: AUCtau of Vemircopan	AUCtau of vermircopan after multiple twice daily doses will be assessed.	Period 2: Days 4, and 5
Secondary	Part 2: tmax of Vemircopan	tmax of vermircopan after multiple twice daily doses will be assessed.	Period 2: Days 4, and 5
Secondary	Part 2: Ctrough of Vemircopan	Ctrough of vermircopan after multiple twice daily doses will be assessed.	Period 2: Days 3, 4, and 5
Secondary	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
Secondary	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
Secondary	Part 3: ?z of Vemircopan	?z 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
Secondary	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
Secondary	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
Secondary	Part 3: Cmax of Carbamazepine	Cmax of carbamazepine after multiple twice daily doses will be assessed.	Period 2: Days 4, 18 and 19
Secondary	Part 3: AUCtau of Carbamazepine	AUCtau of carbamazepine after multiple twice daily doses will be assessed.	Period 2: Days 4, 18 and 19
Secondary	Part 3: tmax of Carbamazepine	tmax of carbamazepine after multiple twice daily doses will be assessed.	Period 2: Days 4, 18 and 19
Secondary	Part 3: Ctrough of Carbamazepine	Ctrough of carbamazepine after multiple twice daily doses will be assessed.	Period 2: Days 18 and 19