Clinical trial NCT03385525: Study to Evaluate the Effect of UGT Inhibition by Valproic Acid on the Pharmacokinetics of BIIB074
Official title: A Phase 1, Open-label, Fixed-sequence Study to Evaluate the Effect of UGT Inhibition by Valproic Acid on the Pharmacokinetics of BIIB074 in Healthy Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Drug Interaction
Keywords: Healthy Volunteer
Lead sponsor: Biogen
Sponsor class: INDUSTRY
First posted: 2017-12-28
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
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 the UGT inhibitor valproic acid on the single-dose pharmacokinetics of BIIB074. The secondary objectives of this study are to evaluate the safety and tolerability of BIIB074 when administered alone and when coadministered with the UGT inhibitor valproic acid and to evaluate the effect of the UGT inhibitor valproic acid 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.
* Must be male, postmenopausal female, or surgically sterile female
* 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 (GI), hematologic, hepatic, immunologic, metabolic, urologic, pulmonary, neurologic, dermatologic, psychiatric, or renal disease, or other major disease, as determined by the Investigator
* Clinically significant abnormal laboratory test values, as determined by the Investigator, at Screening or Day -1
* History of, or positive test result at Screening for, human immunodeficiency virus (HIV)
* Treatment with any prescription or over-the-counter oral medication (excluding acetaminophen) within 14 days prior to Day -1 and an unwillingness or inability to refrain from this treatment during study participation, unless specifically permitted elsewhere within this protocol.
* Other unspecified reasons that, in the opinion of the Investigator or Sponsor, make the subject unsuitable for enrollment.

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply

Primary outcomes:
measure: Maximum Observed Concentration (Cmax) of BIIB074
timeFrame: Day 1 through Day 8, Day 16 through Day 23
measure: Area Under the Concentration-Time Curve from Time 0 to Infinity (AUCinf) of BIIB074
timeFrame: Day 1 through Day 8, Day 16 through Day 23
measure: Area Under the Concentration-Time Curve from Time Zero to Time of the Last Measurable Concentration (AUClast) of BIIB074
timeFrame: Day 1 through Day 8, Day 16 through Day 23
measure: Time to Reach Maximum Observed Concentration (Tmax) for BIIB074
timeFrame: Day 1 through Day 8, Day 16 through Day 23
measure: Time of Last Measured Serum Concentration (Tlast) of BIIB074
timeFrame: Day 1 through Day 8, Day 16 through Day 23
measure: Elimination Half-Life (T 1/2) of BIIB074
timeFrame: Day 1 through Day 8, Day 16 through Day 23
measure: Apparent Clearance (CL/F) of BIIB074
timeFrame: Day 1 through Day 8, Day 16 through Day 23
measure: Apparent Volume of Distribution (V/F) of BIIB074
timeFrame: Day 1 through Day 8, Day 16 through Day 23
Secondary outcomes:
measure: Percentage of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: Up to Day 32
measure: Number of Participants with Abnormal Change from Baseline of Electrocardiogram (ECG) up to Day 23
timeFrame: Day 1, 3, 8, 13, 16, 18, 23
measure: Number of Participants with Abnormal Change from Baseline of Clinical Laboratory Parameters up to Day 23
timeFrame: Day 3, 8, 13, 16, 18, 23
measure: Number of Participants with Abnormal Change from Baseline of Vital Signs up to Day 23
timeFrame: Day 1, 3, 8, 13, 16, 18, 23
measure: Cmax of BIIB074 Metabolites M13, M14, and M16
timeFrame: Day 1 through Day 8, Day 16 through Day 23
measure: AUCinf of BIIB074 Metabolites M13, M14, and M16
timeFrame: Day 1 through Day 8, Day 16 through Day 23
measure: AUClast of BIIB074 Metabolites M13, M14, and M16
timeFrame: Day 1 through Day 8, Day 16 through Day 23
measure: Tmax of BIIB074 Metabolites M13, M14, and M16
timeFrame: Day 1 through Day 8, Day 16 through Day 23
measure: Tlast of BIIB074 Metabolites M13, M14, and M16
timeFrame: Day 1 through Day 8, Day 16 through Day 23
measure: T1/2 of BIIB074 Metabolites M13, M14, and M16
timeFrame: Day 1 through Day 8, Day 16 through Day 23
measure: Metabolite-to-Parent Ratio in AUC (MRauc) of BIIB074 Metabolites M13, M14, and M16
timeFrame: Day 1 through Day 8, Day 16 through Day 23
measure: Number of Participants with Abnormal Change from Baseline in Columbia Suicide Severity Rating (C-SSRS) scale
timeFrame: Day 8, 23, and once between Day 29-32
Other outcomes:
Locations:
city: Dallas
country: United States
facility: Research Site
state: Texas
Study officials:
affiliation: Biogen
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: Zhao Y, Kotecha M, Finnigan H, Serenko M, Naik H. Evaluation of the Effect of Uridine Diphosphate-Glucuronosyltransferases (UGT) Inhibition by Valproic Acid on Vixotrigine Pharmacokinetics in Healthy Volunteers. Clin Drug Investig. 2022 Oct;42(10):829-837. doi: 10.1007/s40261-022-01194-y. Epub 2022 Aug 31.