A Study to Determine the Absolute Bioavailability of BIIB122/DNL151 in Healthy Subjects

Study Overview
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Brief Summary
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This is a single center, non-randomized, open label Phase 1 study to determine the PK and absolute bioavailability of BIIB122 (DNL151) in 2 conditions: following a single, oral dose of BIIB122 (DNL151) and following consecutive days of oral dosing, approximating steady state.

Detailed Description
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This clinical trial information was submitted voluntarily under the applicable law and, therefore, certain submission deadlines may not apply. (That is, clinical trial information for this applicable clinical trial was submitted under section 402(j)(4)(A) of the Public Health Service Act and 42 CFR 11.60 and is not subject to the deadlines established by sections 402(j)(2) and (3) of the Public Health Service Act or 42 CFR 11.24 and 11.44.).

Official Title
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An Open Label Phase 1 Study to Determine the Absolute Bioavailability of Single and Repeated Daily Oral Administration of BIIB122 (DNL151) Utilizing a Microtracer Dose of Intravenously Administered [14C] BIIB122 ([14C] DNL151) to Healthy Subjects

Conditions
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Healthy Volunteers

Intervention / Treatment
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* Drug: BIIB122 (DNL151)
* Drug: [14C] BIIB122 ([14C] DNL151)


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Women of non-childbearing potential and men either with a vasectomy, using contraception, or having sex with a woman of non-childbearing potential Body mass index (BMI) ≥ 18 kg/m2 and ≤ 32 kg/m2 Considered to be in good health Nonsmoker Key Exclusion Criteria: History or presence of any condition or prior surgery that, in the opinion of the investigator, poses a significant risk to subject safety and/or achievement of study objectives

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 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: Cohort A<br> | Drug: BIIB122 (DNL151)<br>* Oral doses<br>Drug: [14C] BIIB122 ([14C] DNL151)<br>* Intravenous doses<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PK Parameter: The first time to maximum observed concentration (Tmax) of BIIB122 (DNL151) in plasma following oral administration |  | 1 day | 
| PK Parameter: Maximum observed concentration (Cmax) of BIIB122 (DNL151) in plasma following oral administration |  | 1 day | 
| PK Parameter: Area under the concentration-time curve (AUC) of BIIB122 (DNL151) and [14C]-BIIB122 ([14C]-DNL151 in plasma following oral and intravenous administration |  | 1 day | 
| PK Parameter: Time from baseline at which half of BIIB122 (DNL151) and [14C]-BIIB122 ([14C]-DNL151 has been eliminated (t1/2) in plasma after oral and intravenous administration |  | 1 day | 
| PK Parameter: Clearance (CL/F and CL) of BIIB122 (DNL151) and [14C]-BIIB122 ([14C]-DNL151) from plasma after oral and intravenous administration |  | 1 day | 
| PK Parameter: Volume of distribution (Vd/F and Vd) of BIIB122 (DNL151) and [14C]-BIIB122 ([14C]-DNL151) from plasma after oral and intravenous administration |  | 1 day | 
| PK Parameter: Absolute bioavailability (F) of BIIB122 (DNL151) after oral administration |  | 1 day | 
| PK Parameter: The first time to maximum observed concentration (Tmax) of BIIB122 (DNL151) in plasma following oral administration |  | 21 days | 
| PK Parameter: Maximum observed concentration (Cmax) of BIIB122 (DNL151) in plasma following oral administration |  | 21 days | 
| PK Parameter: Concentration of BIIB122 (DNL151) in plasma at the end of dosing interval |  | 21 days | 
| PK Parameter: Area under the concentration-time curve of BIIB122 (DNL151) and [14C]-BIIB122 ([14C]-DNL151) in plasma following oral and intravenous administration |  | 21 days | 
| PK Parameter: Time from baseline at which half of BIIB122 (DNL151) and [14C]-BIIB122 ([14C]-DNL151) has been eliminated (t1/2) in plasma after oral and intravenous administration |  | 21 days | 
| PK Parameter: Volume of distribution (Vd/F and Vd) of BIIB122 (DNL151) and [14C]-BIIB122 ([14C]-DNL151) from plasma after oral and intravenous administration |  | 21 days | 
| PK Parameter: Clearance (CL/F and CL) of BIIB122 (DNL151) and [14C]-BIIB122 ([14C]-DNL151) from plasma after oral and intravenous administration |  | 21 days | 
| PK Parameter: Absolute bioavailability (F) of BIIB122 (DNL151) after oral administration |  | 21 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of adverse events (AEs) |  | 31 days | 
| Incidence of serious adverse events (SAEs) |  | 31 days |