Effect of Itraconazole on the Pharmacokinetics of BIIB074

An Open-label, Fixed-sequence, Phase 1 Study of the Effect of CYP3A4 Inhibition by Itraconazole on the Pharmacokinetics of BIIB074 in Healthy Subjects

The primary objective of the study is to assess the effect of cytochrome P450 (CYP) 3A4 inhibition on the pharmacokinetics (PK) of BIIB074. The secondary objectives of this study are to assess the safety and tolerability of BIIB074 when co-administered with a strong CYP3A4 inhibitor and to assess the effect of CYP3A4 inhibition on the PK of 3 metabolites of BIIB074 (CNV3000497 [M13], CNV2283325 [M14], and CNV2288584 [M16]).

Study Overview

• Status: Completed
• Conditions: Neuropathic Pain
• Intervention / Treatment: Drug: BIIB074; Drug: Itraconazole

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • Leeds, United Kingdom, LS2 9LH
    • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Key Inclusion Criteria:

• Body mass index of 18 to 29 kg/m2, inclusive, with body weight ≥50 kg for males and ≥45 kg for females.
• Male or postmenopausal or surgically sterile females.
• Must be in good health as determined by the Investigator (or designee), based on medical history and screening evaluations.

Key Exclusion Criteria:

• Females of childbearing potential.
• 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: BIIB074; Administered orally on Day 1 and Day 11	Drug: BIIB074; Administered as specified in the treatment arm; Other Names: CNV1014802; Drug: Itraconazole; 200 mg twice daily [BID] on Day 8 and once daily (QD) from Day 9 to Day 15 inclusive; Other Names: Sporanox, Onmel

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Maximum observed concentration (Cmax) of BIIB074	Prior to dosing up to 96 hours post dose
Exposure of BIIB074 as measured by area under the concentration-time curve from time zero to infinity (AUCinf)	Prior to dosing up to 96 hours post dose

Secondary Outcome Measures

Outcome Measure	Time Frame
Terminal elimination half-life (t1/2) of BIIB074	96 hours post dose
Apparent total body clearance (CL/F) of BIIB074	96 hours post dose
Apparent volume of distribution (Vd/F) of BIIB074	96 hours post dose
Area under the concentration-time curve from time zero to time of the last measurable drug concentration (AUC0-t) of BIIB074	Prior to dosing up to 96 hours post dose
Time that the maximum observed concentration occurs (Tmax) of BIIB074	Prior to dosing up to 96 hours post dose
Number of participants experiencing adverse events (AEs) and serious adverse events (SAEs)	Up to 25 days
Number of participants with clinically significant vital sign abnormalities	Up to 25 days
Number of participants with clinically significant 12-lead electrocardiograms (ECGs) abnormalities	Up to 25 days
Number of participants with clinically significant laboratory assessment abnormalities	Up to 25 days
Effect of CYP3A4 inhibition on the Cmax of 3 metabolites of BIIB074	Prior to dosing up to 96 hours post dose
Effect of CYP3A4 inhibition on the AUCinf of 3 metabolites of BIIB074	Prior to dosing up to 96 hours post dose
Effect of CYP3A4 inhibition on the AUC0-t of CNV3000497 (M13)	Prior to dosing up to 96 hours post dose
Effect of CYP3A4 inhibition on the AUC0-t of CNV2283325 (M14)	Prior to dosing up to 96 hours post dose
Effect of CYP3A4 inhibition on the AUC0-t of CNV2288584 (M16)	Prior to dosing up to 96 hours post dose
Effect of CYP3A4 inhibition on the Tmax of CNV3000497 (M13)	Prior to dosing up to 96 hours post dose
Effect of CYP3A4 inhibition on the Tmax of CNV2283325 (M14)	Prior to dosing up to 96 hours post dose
Effect of CYP3A4 inhibition on the Tmax of CNV2288584 (M16)	Prior to dosing up to 96 hours post dose
Effect of CYP3A4 inhibition on the t1/2 of CNV3000497 (M13)	Prior to dosing up to 96 hours post dose
Effect of CYP3A4 inhibition on the t1/2 of CNV2283325 (M14)	Prior to dosing up to 96 hours post dose
Effect of CYP3A4 inhibition on the t1/2 of CNV2288584 (M16)	Prior to dosing up to 96 hours post dose

Collaborators and Investigators

• Sponsor: Biogen

Study record dates

Study Major Dates

• Study Start: February 1, 2016
• Primary Completion (Actual): April 1, 2016
• Study Completion (Actual): April 1, 2016

Study Registration Dates

• First Submitted: February 29, 2016
• First Submitted That Met QC Criteria: February 29, 2016
• First Posted (Estimate): March 3, 2016

Study Record Updates

• Last Update Posted (Estimate): June 9, 2016
• Last Update Submitted That Met QC Criteria: June 7, 2016
• Last Verified: June 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Pain; Neurologic Manifestations; Neuromuscular Diseases; Peripheral Nervous System Diseases; Neuralgia; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Hormones, Hormone Substitutes, and Hormone Antagonists; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Hormone Antagonists; Antifungal Agents; Steroid Synthesis Inhibitors; 14-alpha Demethylase Inhibitors; Itraconazole
• Other Study ID Numbers: 802HV104; 2015-005096-25 (EudraCT Number)