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

Drug Interaction Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03385525
• Other study ID #: 802HV109
• Status: Completed
• Phase: Phase 1
• First received: October 13, 2017
• Last updated: April 18, 2018
• Start date: September 12, 2017
• Est. completion date: October 13, 2017

Study information

• Verified date: April 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 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 30
• Est. completion date: October 13, 2017
• Est. primary completion date: October 13, 2017
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

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

Related Conditions & MeSH terms

• Drug Interaction

Intervention

Drug:
• BIIB074
Administered as specified in the treatment arm
• Valproic Acid
Administered as specified in the treatment arm

Locations

Country	Name	City	State
United States	Research Site	Dallas	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Biogen

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum Observed Concentration (Cmax) of BIIB074		Day 1 through Day 8, Day 16 through Day 23
Primary	Area Under the Concentration-Time Curve from Time 0 to Infinity (AUCinf) of BIIB074		Day 1 through Day 8, Day 16 through Day 23
Primary	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
Primary	Time to Reach Maximum Observed Concentration (Tmax) for BIIB074		Day 1 through Day 8, Day 16 through Day 23
Primary	Time of Last Measured Serum Concentration (Tlast) of BIIB074		Day 1 through Day 8, Day 16 through Day 23
Primary	Elimination Half-Life (T 1/2) of BIIB074		Day 1 through Day 8, Day 16 through Day 23
Primary	Apparent Clearance (CL/F) of BIIB074		Day 1 through Day 8, Day 16 through Day 23
Primary	Apparent Volume of Distribution (V/F) of BIIB074		Day 1 through Day 8, Day 16 through Day 23
Secondary	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
Secondary	Number of Participants with Abnormal Change from Baseline of Electrocardiogram (ECG) up to Day 23		Day 1, 3, 8, 13, 16, 18, 23
Secondary	Number of Participants with Abnormal Change from Baseline of Clinical Laboratory Parameters up to Day 23		Day 3, 8, 13, 16, 18, 23
Secondary	Number of Participants with Abnormal Change from Baseline of Vital Signs up to Day 23		Day 1, 3, 8, 13, 16, 18, 23
Secondary	Cmax of BIIB074 Metabolites M13, M14, and M16		Day 1 through Day 8, Day 16 through Day 23
Secondary	AUCinf of BIIB074 Metabolites M13, M14, and M16		Day 1 through Day 8, Day 16 through Day 23
Secondary	AUClast of BIIB074 Metabolites M13, M14, and M16		Day 1 through Day 8, Day 16 through Day 23
Secondary	Tmax of BIIB074 Metabolites M13, M14, and M16		Day 1 through Day 8, Day 16 through Day 23
Secondary	Tlast of BIIB074 Metabolites M13, M14, and M16		Day 1 through Day 8, Day 16 through Day 23
Secondary	T1/2 of BIIB074 Metabolites M13, M14, and M16		Day 1 through Day 8, Day 16 through Day 23
Secondary	Metabolite-to-Parent Ratio in AUC (MRauc) of BIIB074 Metabolites M13, M14, and M16		Day 1 through Day 8, Day 16 through Day 23
Secondary	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