Healthy Participants
Conditions
Keywords
Drug-drug interaction, Pharmacokinetic
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.
Interventions
DRUGVemircopan
Participants will receive oral tablets of Vemircopan.
DRUGRosuvastatin
Participants will receive oral coated tablets of Rosuvastatin.
DRUGMetformin
Participants will receive oral film-coated tablets of Metformin.
DRUGLevonorgestrel / Ethinyl Estradiol
Participants will receive oral tablets of Levonorgestrel/ Ethinyl Estradiol.
DRUGCarbamazepine
Participants will receive oral chewable tablets of Carbamazepine.
Sponsors
Alexion Pharmaceuticals, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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
| Measure | Time frame | Description |
|---|---|---|
| Part 1: tmax of Vemircopan | Period 2: Days 4, 5 and 8 | tmax of vermircopan after multiple twice daily doses will be assessed. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| Part 2: Cmax of Vemircopan | Period 2: Days 4, and 5 | Cmax of vermircopan after multiple twice daily doses will be assessed. |
| Part 2: AUCtau of Vemircopan | Period 2: Days 4, and 5 | AUCtau of vermircopan after multiple twice daily doses will be assessed. |
| Part 2: tmax of Vemircopan | Period 2: Days 4, and 5 | tmax of vermircopan after multiple twice daily doses will be assessed. |
| Part 2: Ctrough of Vemircopan | Period 2: Days 3, 4, and 5 | Ctrough of vermircopan after multiple twice daily doses will be assessed. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| Part 3: Cmax of Carbamazepine | Period 2: Days 4, 18 and 19 | Cmax of carbamazepine after multiple twice daily doses will be assessed. |
| Part 3: AUCtau of Carbamazepine | Period 2: Days 4, 18 and 19 | AUCtau of carbamazepine after multiple twice daily doses will be assessed. |
| Part 3: tmax of Carbamazepine | Period 2: Days 4, 18 and 19 | tmax of carbamazepine after multiple twice daily doses will be assessed. |
| Part 3: Ctrough of Carbamazepine | Period 2: Days 18 and 19 | Ctrough of carbamazepine after multiple twice daily doses will be assessed. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| Part 1: Cmax of Vemircopan | Period 2: Days 4, 5 and 8 | Cmax of vermircopan after multiple twice daily doses will be assessed. |
| 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. |
Countries
United States
Outcome results
None listed