A Drug Interaction Study of BIIB074 and an Oral Contraceptive Regimen

A Phase 1 Study to Evaluate the Pharmacokinetic Interaction Potential Between BIIB074 and an Oral Contraceptive Regimen in Healthy Female Subjects

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.

Study Overview

• Status: Completed
• Conditions: Drug Interactions
• Intervention / Treatment: Drug: BIIB074; Drug: OC (ethinyl estradiol and levonorgestrel)

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Daytona Beach, Florida, United States, 32117
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: BIIB074 150 mg and Oral Contraceptive; Participants will receive BIIB074 in tablet form in 150 mg doses every 8 hours on prescription (TID) on days 1-7 and on days 26-32. OC will be taken in tablet form (ethinyl estradiol 30 micrograms and levonorgestrel 150 micrograms) once daily (QD) on days 12-32.	Drug: BIIB074; BIIB074 is administered as specified in the treatment arm.; Drug: OC (ethinyl estradiol and levonorgestrel); OC is administered as specified in the treatment arm.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Area Under the Concentration-Time Curve from Hour 0 to Hour 8 (AUC8) for BIIB074	Day 7, 32
Area Under the Concentration-Time Curve from Hour 0 to Hour 24 (AUC24) for OC	Day 25, 32
Maximum Observed Concentration (Cmax) for BIIB074	Day 7, 32
Maximum Observed Concentration (Cmax) for OC	Day 25, 32
Time to Reach Maximum Observed Concentration (Tmax) for BIIB074	Day 7, 32
Terminal Elimination Half-Life (t1/2) of BIIB074	Day 7, 32
Apparent Clearance (CL/F) for BIIB074	Day 7, 32
Apparent Volume of Distribution at Steady State (Vss/F) for BIIB074	Day 7, 32
Time to Maximum Observed Concentration (Tmax) for OC	Day 25, 32
Terminal Elimination Half-Life (t1/2) of OC	Day 25, 32
Apparent Clearance (CL/F) for OC	Day 25, 32
Apparent Volume of Distribution at Steady State (Vss/F) for OC	Day 25, 32

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)	An AE is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment.	Approximately 71 days
Number of Participants with Abnormal Change from Baseline in Laboratory Parameters up to Day 33	Chemistry panel included total protein, albumin, creatinine, blood urea nitrogen, uric acid, bilirubin (total and direct), alkaline phosphatase, ALT, AST, gamma-glutamyl transferase, glucose, calcium, phosphorus, bicarbonate, chloride, sodium, and potassium.	Day 3, 7, 24, 28, 33
Number of Participants with Abnormal Change from Baseline in Hematology Panel up to Day 33	Hematology Panel measurements are complete blood count with differential and platelet count, and absolute neutrophil count	Day 3, 7, 24, 28, 33
Number of Participants with Abnormal Change from Baseline in Urinalysis Panel up to Day 33	Urinalysis panel included dipstick for occult blood, protein, nitrites, leukocyte esterase, glucose, bilirubin, urobilinogen, ketones, pH, and specific gravity. A microscopic examination will be performed if occult blood, protein, nitrites, or leukocyte esterase is abnormal.	Day 3, 7, 24, 28, 33
Number of Participants with Abnormal Change from Baseline in Vital Sign Measurements up to Day 33	Vital signs measurements are temperature, heart rate, systolic and diastolic blood pressure, and respiratory rate	Day 1, 3, 7, 12, 24, 25, 26, 28, 33
Number of Participants with Abnormal Change from Baseline in Electrocardiogram (ECG) up to Day 33	12-lead ECGs measurements are heart rate, PR interval, RR interval, QRS duration, QT interval, and QTcF	Day 1, 3, 7, 12, 25, 26, 28, 33
Number of Participants with Abnormal Change from Baseline in Physical Examination up to Day 33	Abnormal physical examinations findings that are noted postbaseline and deemed clinically significant by the Investigator will be reported as AEs and will be included in the AE analyses.	Day -1, 33
AUC 8 of BIIB074 Metabolites M13, M14, and M16	AUC8 indicates the actual body exposure to BIIB074 metabolites during 8 hours after administration of a BIIB074 dose and is expressed in mg*h/L.	Day 7, 32
Cmax for BIIB074 Metabolites M13, M14, and M16	Cmax is the maximum serum concentration that BIIB074 metabolites M13, 14, and 16 achieves in the body after BIIB074 is administered.	Day 7, 32
Tmax for BIIB074 Metabolites M13, M14, and M16	Tmax is the amount of time it takes to reach Cmax of the BIIB074 metabolites13,14, and 16 after BIIB074 has been administered.	Day 7, 32
Terminal Elimination Half-Life (T 1/2) for BIIB074 Metabolites M13, M14, and M16	The terminal elimination half-life is the time required to divide the plasma concentration of BIIB074 metabolites M13,14,and 16 by two after reaching pseudo-equilibrium.	Day 7, 32
Metabolite-to-Parent Ratio in AUC (MRauc) for BIIB074 Metabolites M13, M14, and M16	The MRauc is the ratio of the BIIB074 metabolites M13,14,and 16 to BIIB074 after administration	Day 7, 32
Number of Participants with Abnormal Change from Baseline in Columbia Suicide Severity Rating Scale (C-SSRS) Assessments	The C-SSRS captures the occurrence, severity, and frequency of suicide-related thoughts and behaviors during the assessment period.	Day 7, 12, 24, 33, and once between Day 39-42

Collaborators and Investigators

• Sponsor: Biogen

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): November 11, 2017
• Primary Completion (Actual): March 15, 2018
• Study Completion (Actual): March 15, 2018

Study Registration Dates

• First Submitted: October 25, 2017
• First Submitted That Met QC Criteria: October 25, 2017
• First Posted (Actual): October 30, 2017

Study Record Updates

• Last Update Posted (Actual): September 25, 2018
• Last Update Submitted That Met QC Criteria: September 24, 2018
• Last Verified: September 1, 2018

More Information

Terms related to this study

• Keywords: Levonorgestrel; Oral Contraceptive, Healthy Volunteers, Ethinyl Estradiol,
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Estrogens; Contraceptive Agents, Hormonal; Contraceptive Agents; Reproductive Control Agents; Contraceptives, Oral; Contraceptive Agents, Female; Contraceptives, Oral, Synthetic; Contraceptives, Oral, Hormonal; Levonorgestrel; Estradiol; Ethinyl Estradiol
• Other Study ID Numbers: 802HV108

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No