Effect of Itraconazole on the Pharmacokinetics of BIIB074

Study Overview
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Brief Summary
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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]).

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

Conditions
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Neuropathic Pain

Intervention / Treatment
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* Drug: BIIB074
* Drug: Itraconazole


Participation Criteria
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Eligibility Criteria
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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.

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<br>Administered orally on Day 1 and Day 11 | Drug: BIIB074<br>* Administered as specified in the treatment arm<br>* Other names: CNV1014802;Drug: Itraconazole<br>* 200 mg twice daily [BID] on Day 8 and once daily (QD) from Day 9 to Day 15 inclusive<br>* Other names: Sporanox, Onmel;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 | Measure Description | 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 |