Study to Evaluate the Effect of UGT Inhibition by Valproic Acid on the Pharmacokinetics of BIIB074

NCT03385525 | Completed Phase 1 FDA Drug

• 1 other identifier: 802HV109
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

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.

Conditions

Drug Interaction

Keywords

Healthy Volunteer

Outcome Measures

Primary Outcomes (8)

• Maximum Observed Concentration (Cmax) of BIIB074

  Day 1 through Day 8, Day 16 through Day 23

• Area Under the Concentration-Time Curve from Time 0 to Infinity (AUCinf) of BIIB074

  Day 1 through Day 8, Day 16 through Day 23

• Area Under the Concentration-Time Curve from Time Zero to Time of the Last Measurable Concentration (AUClast) of BIIB074

  Day 1 through Day 8, Day 16 through Day 23

• Time to Reach Maximum Observed Concentration (Tmax) for BIIB074

  Day 1 through Day 8, Day 16 through Day 23

• Time of Last Measured Serum Concentration (Tlast) of BIIB074

  Day 1 through Day 8, Day 16 through Day 23

• Elimination Half-Life (T 1/2) of BIIB074

  Day 1 through Day 8, Day 16 through Day 23

• Apparent Clearance (CL/F) of BIIB074

  Day 1 through Day 8, Day 16 through Day 23

• Apparent Volume of Distribution (V/F) of BIIB074

  Day 1 through Day 8, Day 16 through Day 23

Secondary Outcomes (12)

• Percentage of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)

  Up to Day 32

• Number of Participants with Abnormal Change from Baseline of Electrocardiogram (ECG) up to Day 23

  Day 1, 3, 8, 13, 16, 18, 23

• Number of Participants with Abnormal Change from Baseline of Clinical Laboratory Parameters up to Day 23

  Day 3, 8, 13, 16, 18, 23

• Number of Participants with Abnormal Change from Baseline of Vital Signs up to Day 23

  Day 1, 3, 8, 13, 16, 18, 23

• Cmax of BIIB074 Metabolites M13, M14, and M16

  Day 1 through Day 8, Day 16 through Day 23

Study Arms (1)

BIIB074 150 mg and Valproic Acid 500 mg

EXPERIMENTAL

Participants will receive BIIB074 in tablet form in 150 mg doses. BIIB074 will be taken once daily (QD) on Days 1-16 after an 8-hour fast. Valproic Acid will be given in capsule form in 500 mg doses on prescription (TID) every 8 hours on Days 8-22. The morning dose on Day 16 will be coadministered with BIIB074 following an 8-hour fast.

Drug: BIIB074; Drug: Valproic Acid

Interventions

BIIB074 DRUG

Administered as specified in the treatment arm

BIIB074 150 mg and Valproic Acid 500 mg

Valproic Acid DRUG

Administered as specified in the treatment arm

Also known as: Depakote, Depakene, Stavzor, and Valproic

BIIB074 150 mg and Valproic Acid 500 mg

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Biogen: lead

Study Sites (1)

Research Site

Dallas, Texas, 75247, United States

Location

Related Publications (1)

• 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.

  PMID: 36045316 DERIVED

MeSH Terms

Interventions

vixotrigine; Valproic Acid

Intervention Hierarchy (Ancestors)

Pentanoic Acids; Valerates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Fatty Acids, Volatile; Fatty Acids; Lipids

Study Officials

• Medical Director

  Biogen

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 13, 2017
• First Posted: December 28, 2017
• Study Start: September 12, 2017
• Primary Completion: October 13, 2017
• Study Completion: October 13, 2017
• Last Updated: April 20, 2018

Record last verified: 2018-04

Locations

US (1)