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

• Sponsor: Alexion (Industry)
• Overall Status: Not yet recruiting
• CT.gov ID: NCT06071442
• Collaborator: (none)
• Enrollment: 60
• Arms: 3
• Anticipated Duration (Months): 5.9

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Healthy Participants	Drug: Vemircopan; Drug: Rosuvastatin; Drug: Metformin; Drug: Levonorgestrel / Ethinyl Estradiol; Drug: Carbamazepine	Phase 1

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 Design

• Study Type: Interventional
• Anticipated Enrollment: 60 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Anticipated Study Start Date: Oct 5, 2023
• Anticipated Primary Completion Date: Apr 1, 2024
• Anticipated Study Completion Date: Apr 1, 2024

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures

1. Part 1: Maximum observed plasma (peak) concentration (Cmax) of Metformin [Up to 48 hours post-dose]

   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.

2. Part 1: AUC from time zero to the last quantifiable concentration (AUCt) of Metformin [Up to 48 hours post-dose]

   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.

3. Part 1: AUC from time zero extrapolated to infinity (AUC∞) of Metformin [Up to 48 hours post-dose]

   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.

4. Part 1: Cmax of Rosuvastatin [Up to 96 hours post-dose]

   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.

5. Part 1: AUCt of Rosuvastatin [Up to 96 hours post-dose]

   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.

6. Part 1: AUC∞ of Rosuvastatin [Up to 96 hours post-dose]

   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.

7. Part 2: Cmax of LNG [Up to 120 hours post-dose]

   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.

8. Part 2: AUCt of LNG [Up to 120 hours post-dose]

   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.

9. Part 2: AUC∞ of LNG [Up to 120 hours post-dose]

   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.

10. Part 2: Cmax of EE [Up to 120 hours post-dose]

    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.

11. Part 2: AUCt of EE [Up to 120 hours post-dose]

    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.

12. Part 2: AUC∞ of EE [Up to 120 hours post-dose]

    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.

13. Part 3: Cmax of Vemircopan [Up to 72 hours post-dose]

    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.

14. Part 3: AUCt of Vemircopan [Up to 72 hours post-dose]

    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.

15. Part 3: AUC∞ of Vemircopan [Up to 72 hours post-dose]

    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.

Secondary Outcome Measures

1. Part 1: Number of participants with Treatment Emergent Adverse Events [From Screening (Day -28 to Day -2) up to follow-up Visit or early discontinuation visit (approximately 57 days)]

   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.

2. Part 2: Number of participants with Treatment Emergent Adverse Events [From Screening (Day -28 to Day -2) up to follow-up Visit or early discontinuation visit (approximately 54 days)]

   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.

3. Part 3: Number of participants with Treatment Emergent Adverse Events [From Screening (Day -28 to Day -2) up to follow-up Visit or early discontinuation visit (approximately 63 days)]

   The safety and tolerability of multiple doses of vemircopan when co-administered with multiple doses of carbamazepine will be assessed.

4. Part 1: Time corresponding to the occurrence of Cmax (tmax) of Metformin [Up to 48 hours post-dose]

   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.

5. Part 1: Apparent terminal elimination half-life (t½) of Metformin [Up to 48 hours post-dose]

   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.

6. Part 1: Terminal elimination rate constant (λz) of Metformin [Up to 48 hours post-dose]

   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.

7. Part 1: Volume of distribution (apparent) following extravascular administration (Vd/F) of Metformin [Up to 48 hours post-dose]

   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.

8. Part 1: Apparent total body clearance of drug from plasma after extravascular administration (CL/F) of Metformin [Up to 48 hours post-dose]

   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.

9. Part 1: tmax of Rosuvastatin [Up to 96 hours post-dose]

   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.

10. Part 1: t½ of Rosuvastatin [Up to 96 hours post-dose]

    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.

11. Part 1: λz of Rosuvastatin [Up to 96 hours post-dose]

    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.

12. Part 1: Vd/F of Rosuvastatin [Up to 96 hours post-dose]

    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.

13. Part 1: CL/F of Rosuvastatin [Up to 96 hours post-dose]

    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.

14. Part 1: Cmax of Vemircopan [Period 2: Days 4, 5 and 8]

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

15. Part 1: AUC during a dosing interval at steady state (AUCtau) of Vemircopan [Period 2: Days 4, 5 and 8]

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

16. Part 1: tmax of Vemircopan [Period 2: Days 4, 5 and 8]

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

17. Part 1: Predose concentration prior to morning dose (Ctrough) of Vemircopan [Period 2: Days 3, 4, 5 and 8]

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

18. Part 2: tmax of LNG [Up to 120 hours post-dose]

    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.

19. Part 2: t½ of LNG [Up to 120 hours post-dose]

    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.

20. Part 2: λz of LNG [Up to 120 hours post-dose]

    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.

21. Part 2: Vd/F of LNG [Up to 120 hours post-dose]

    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.

22. Part 2: CL/F of LNG [Up to 120 hours post-dose]

    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.

23. Part 2: tmax of EE [Up to 120 hours post-dose]

    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.

24. Part 2: t½ of EE [Up to 120 hours post-dose]

    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.

25. Part 2: λz of EE [Up to 120 hours post-dose]

    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.

26. Part 2: Vd/F of EE [Up to 120 hours post-dose]

    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.

27. Part 2: CL/F of EE [Up to 120 hours post-dose]

    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.

28. Part 2: Cmax of Vemircopan [Period 2: Days 4, and 5]

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

29. Part 2: AUCtau of Vemircopan [Period 2: Days 4, and 5]

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

30. Part 2: tmax of Vemircopan [Period 2: Days 4, and 5]

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

31. Part 2: Ctrough of Vemircopan [Period 2: Days 3, 4, and 5]

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

32. Part 3: tmax of Vemircopan [Up to 72 hours post-dose]

    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.

33. Part 3: t½ of Vemircopan [Up to 72 hours post-dose]

    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.

34. Part 3: λz of Vemircopan [Up to 72 hours post-dose]

    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.

35. Part 3: Vd/F of Vemircopan [Up to 72 hours post-dose]

    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.

36. Part 3: CL/F of Vemircopan [Up to 96 hours post-dose]

    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.

37. Part 3: Cmax of Carbamazepine [Period 2: Days 4, 18 and 19]

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

38. Part 3: AUCtau of Carbamazepine [Period 2: Days 4, 18 and 19]

    AUCtau of carbamazepine after multiple twice daily doses will be assessed.

39. Part 3: tmax of Carbamazepine [Period 2: Days 4, 18 and 19]

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

40. Part 3: Ctrough of Carbamazepine [Period 2: Days 18 and 19]

    Ctrough of carbamazepine after multiple twice daily doses will be assessed.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 55 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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.

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Alexion

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Alexion
• ClinicalTrials.gov Identifier: NCT06071442
• Other Study ID Numbers: D7841C00012
• First Posted: Oct 6, 2023
• Last Update Posted: Oct 6, 2023
• Last Verified: Oct 1, 2023

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Alexion: Drug-drug interaction; Pharmacokinetic
• Additional relevant MeSH terms: Metformin; Carbamazepine; Rosuvastatin Calcium; Levonorgestrel; Ethinyl Estradiol; Estradiol

Study Results

No Results Posted as of Oct 6, 2023