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CompletedNCT03324685Updated Sep 25, 2018

A Drug Interaction Study of BIIB074 and an Oral Contraceptive Regimen

A Phase 1 interventional study of BIIB074 and OC (ethinyl estradiol and levonorgestrel) in Drug Interactions, sponsored by Biogen. Completed at 1 site in United States. Open to female participants aged 18 Years to 45 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2018-09-25.

Sponsored by Biogen · Phase 1, Interventional, and Treatment

Phase
Phase 1
Study type
Interventional
Enrollment
36
Allocation
Not applicable
Ages
18 Years to 45 Years
Sex
Female
01

Study 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.

02

Conditions studied

  • Drug Interactions

Keywords

  • Oral Contraceptive, Healthy Volunteers, Ethinyl Estradiol,
  • Levonorgestrel
03

Who can participate

Ages eligible
18 Years to 45 Years
Sexes eligible
Female
Accepts healthy volunteers
Yes

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

04

Study design

Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
36 participants (actual)

Study arms

  • 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 · Drug: OC (ethinyl estradiol and levonorgestrel)

Interventions

  • DrugBIIB074

    BIIB074 is administered as specified in the treatment arm.

  • DrugOC (ethinyl estradiol and levonorgestrel)

    OC is administered as specified in the treatment arm.

05

What researchers measure

Primary outcomes

  1. Area Under the Concentration-Time Curve from Hour 0 to Hour 8 (AUC8) for BIIB074

    Time frame: Day 7, 32

  2. Area Under the Concentration-Time Curve from Hour 0 to Hour 24 (AUC24) for OC

    Time frame: Day 25, 32

  3. Maximum Observed Concentration (Cmax) for BIIB074

    Time frame: Day 7, 32

  4. Maximum Observed Concentration (Cmax) for OC

    Time frame: Day 25, 32

  5. Time to Reach Maximum Observed Concentration (Tmax) for BIIB074

    Time frame: Day 7, 32

  6. Terminal Elimination Half-Life (t1/2) of BIIB074

    Time frame: Day 7, 32

  7. Apparent Clearance (CL/F) for BIIB074

    Time frame: Day 7, 32

  8. Apparent Volume of Distribution at Steady State (Vss/F) for BIIB074

    Time frame: Day 7, 32

  9. Time to Maximum Observed Concentration (Tmax) for OC

    Time frame: Day 25, 32

  10. Terminal Elimination Half-Life (t1/2) of OC

    Time frame: Day 25, 32

  11. Apparent Clearance (CL/F) for OC

    Time frame: Day 25, 32

  12. Apparent Volume of Distribution at Steady State (Vss/F) for OC

    Time frame: Day 25, 32

Secondary outcomes

  1. 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.

    Time frame: Approximately 71 days

  2. 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.

    Time frame: Day 3, 7, 24, 28, 33

  3. 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

    Time frame: Day 3, 7, 24, 28, 33

  4. 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.

    Time frame: Day 3, 7, 24, 28, 33

  5. 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

    Time frame: Day 1, 3, 7, 12, 24, 25, 26, 28, 33

  6. 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

    Time frame: Day 1, 3, 7, 12, 25, 26, 28, 33

  7. 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.

    Time frame: Day -1, 33

  8. 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.

    Time frame: Day 7, 32

  9. 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.

    Time frame: Day 7, 32

  10. 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.

    Time frame: Day 7, 32

  11. 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.

    Time frame: Day 7, 32

  12. 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

    Time frame: Day 7, 32

  13. 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.

    Time frame: Day 7, 12, 24, 33, and once between Day 39-42

06

Study locations

1 site
  • Research Site
    Daytona Beach, Florida 32117, United States
07

References and documents

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. PubMed 32564301 ↗
08

Registry details

Key details

Study ID
NCT03324685
Lead sponsor
Biogen
Responsible party
Sponsor
First posted
Oct 30, 2017
Start date
Nov 11, 2017
Primary completion
Mar 15, 2018
Completion
Mar 15, 2018
Last update
Sep 25, 2018

Study contacts

Medical Director
study director · Biogen

Oversight

FDA-regulated drug
Yes
FDA-regulated device
No
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