A Drug Interaction Study of BIIB074 and an Oral Contraceptive Regimen

Drug Interactions Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03324685
• Other study ID #: 802HV108
• Status: Completed
• Phase: Phase 1
• Start date: November 11, 2017
• Est. completion date: March 15, 2018

Study information

• Verified date: September 2018
• Source: Biogen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 36
• Est. completion date: March 15, 2018
• Est. primary completion date: March 15, 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years to 45 Years

Eligibility

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

Related Conditions & MeSH terms

• Drug Interactions

Intervention

Drug:
• BIIB074
BIIB074 is administered as specified in the treatment arm.
• OC (ethinyl estradiol and levonorgestrel)
OC is administered as specified in the treatment arm.

Locations

Country	Name	City	State
United States	Research Site	Daytona Beach	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Biogen

Country where clinical trial is conducted

United States, 

Outcome

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