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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Drug Interaction

Intervention / Treatment
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* Drug: BIIB074
* Drug: Valproic Acid


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BIIB074 150 mg and Valproic Acid 500 mg<br>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<br>* Administered as specified in the treatment arm<br>Drug: Valproic Acid<br>* Administered as specified in the treatment arm<br>* Other names: Depakote, Depakene, Stavzor, and Valproic;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage 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. | 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 | 
| AUCinf of BIIB074 Metabolites M13, M14, and M16 |  | Day 1 through Day 8, Day 16 through Day 23 | 
| AUClast of BIIB074 Metabolites M13, M14, and M16 |  | Day 1 through Day 8, Day 16 through Day 23 | 
| Tmax of BIIB074 Metabolites M13, M14, and M16 |  | Day 1 through Day 8, Day 16 through Day 23 | 
| Tlast of BIIB074 Metabolites M13, M14, and M16 |  | Day 1 through Day 8, Day 16 through Day 23 | 
| T1/2 of BIIB074 Metabolites M13, M14, and M16 |  | Day 1 through Day 8, Day 16 through Day 23 | 
| Metabolite-to-Parent Ratio in AUC (MRauc) of BIIB074 Metabolites M13, M14, and M16 |  | Day 1 through Day 8, Day 16 through Day 23 | 
| Number of Participants with Abnormal Change from Baseline in Columbia Suicide Severity Rating (C-SSRS) scale | C-SSRS is a suicidal ideation rating used to evaluate suicidality in children ages 12 and up. It rates an individual's degree of suicidal ideation on a scale, ranging from wish to be dead to active suicidal ideation with specific plan and intent | Day 8, 23, and once between Day 29-32 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Healthy Volunteer