Clinical trial NCT03324685: A Drug Interaction Study of BIIB074 and an Oral Contraceptive Regimen
Official title: A Phase 1 Study to Evaluate the Pharmacokinetic Interaction Potential Between BIIB074 and an Oral Contraceptive Regimen in Healthy Female Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Drug Interactions
Keywords: Oral Contraceptive, Healthy Volunteers, Ethinyl Estradiol,
Levonorgestrel
Lead sponsor: Biogen
Sponsor class: INDUSTRY
First posted: 2017-10-30
Enrollment: 36
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The primary objective of this study is to evaluate the effect of multiple doses of a uridine diphosphate glucuronosyltransferases (UGT)-inducing oral contraceptive (OC) regimen (ethinyl estradiol and levonorgestrel) on the PK of BIIB074 at steady state; evaluate the effect of multiple doses of BIIB074 on the pharmacokinetics(PK) of an OC regimen (ethinyl estradiol and levonorgestrel) at steady state.

The secondary objective of this study is to evaluate the safety and tolerability of BIIB074 when administered alone and when coadministered with a UGT-inducing OC regimen containing ethinyl estradiol and levonorgestrel and to evaluate the effect of a UGT-inducing OC regimen (ethinyl estradiol and levonorgestrel) on the PK of the M13, M14, and M16 metabolites of BIIB074.


Eligibility criteria: Key Inclusion Criteria:

* Must have a body mass index between 18 and 32 kg/m\^2, inclusive.
* Females of childbearing potential must practice effective non-hormonal contraception during the study and be willing and able to continue contraception for 5 weeks after their last dose of study treatment,
* Must be in good health as determined by the Investigator, based on medical history and screening evaluations.

Key Exclusion Criteria:

* History of any clinically significant cardiac, endocrine, gastrointestinal, hematologic, hepatic, immunologic, metabolic, urologic, pulmonary, neurologic, dermatologic, psychiatric, or renal disease, or other major disease, as determined by the Investigator.
* History of, or positive test result at Screening for, human immunodeficiency virus (HIV)
* Clinically significant abnormal laboratory test values, as determined by the Investigator, at Screening or Day -1
* Previous intolerance to OC medications
* Other unspecified reasons that, in the opinion of the Investigator or Biogen, make the subject unsuitable for enrollment.

NOTE:Other protocol defined Inclusion/Exclusion criteria may apply

Primary outcomes:
measure: Area Under the Concentration-Time Curve from Hour 0 to Hour 8 (AUC8) for BIIB074
timeFrame: Day 7, 32
measure: Area Under the Concentration-Time Curve from Hour 0 to Hour 24 (AUC24) for OC
timeFrame: Day 25, 32
measure: Maximum Observed Concentration (Cmax) for BIIB074
timeFrame: Day 7, 32
measure: Maximum Observed Concentration (Cmax) for OC
timeFrame: Day 25, 32
measure: Time to Reach Maximum Observed Concentration (Tmax) for BIIB074
timeFrame: Day 7, 32
measure: Terminal Elimination Half-Life (t1/2) of BIIB074
timeFrame: Day 7, 32
measure: Apparent Clearance (CL/F) for BIIB074
timeFrame: Day 7, 32
measure: Apparent Volume of Distribution at Steady State (Vss/F) for BIIB074
timeFrame: Day 7, 32
measure: Time to Maximum Observed Concentration (Tmax) for OC
timeFrame: Day 25, 32
measure: Terminal Elimination Half-Life (t1/2) of OC
timeFrame: Day 25, 32
measure: Apparent Clearance (CL/F) for OC
timeFrame: Day 25, 32
measure: Apparent Volume of Distribution at Steady State (Vss/F) for OC
timeFrame: Day 25, 32
Secondary outcomes:
measure: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: Approximately 71 days
measure: Number of Participants with Abnormal Change from Baseline in Laboratory Parameters up to Day 33
timeFrame: Day 3, 7, 24, 28, 33
measure: Number of Participants with Abnormal Change from Baseline in Hematology Panel up to Day 33
timeFrame: Day 3, 7, 24, 28, 33
measure: Number of Participants with Abnormal Change from Baseline in Urinalysis Panel up to Day 33
timeFrame: Day 3, 7, 24, 28, 33
measure: Number of Participants with Abnormal Change from Baseline in Vital Sign Measurements up to Day 33
timeFrame: Day 1, 3, 7, 12, 24, 25, 26, 28, 33
measure: Number of Participants with Abnormal Change from Baseline in Electrocardiogram (ECG) up to Day 33
timeFrame: Day 1, 3, 7, 12, 25, 26, 28, 33
measure: Number of Participants with Abnormal Change from Baseline in Physical Examination up to Day 33
timeFrame: Day -1, 33
measure: AUC 8 of BIIB074 Metabolites M13, M14, and M16
timeFrame: Day 7, 32
measure: Cmax for BIIB074 Metabolites M13, M14, and M16
timeFrame: Day 7, 32
measure: Tmax for BIIB074 Metabolites M13, M14, and M16
timeFrame: Day 7, 32
measure: Terminal Elimination Half-Life (T 1/2) for BIIB074 Metabolites M13, M14, and M16
timeFrame: Day 7, 32
measure: Metabolite-to-Parent Ratio in AUC (MRauc) for BIIB074 Metabolites M13, M14, and M16
timeFrame: Day 7, 32
measure: Number of Participants with Abnormal Change from Baseline in Columbia Suicide Severity Rating Scale (C-SSRS) Assessments
timeFrame: Day 7, 12, 24, 33, and once between Day 39-42
Other outcomes:
Locations:
city: Daytona Beach
country: United States
facility: Research Site
state: Florida
Study officials:
affiliation: Biogen
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: Zhao Y, Versavel M, Tidemann-Miller B, Christmann R, Naik H. Evaluation of the Potential Pharmacokinetic Interactions Between Vixotrigine and an Oral Contraceptive. Clin Drug Investig. 2020 Aug;40(8):737-746. doi: 10.1007/s40261-020-00931-5.