A Phase 1, Single-Ascending-Dose, Safety, Tolerability, Pharmacokinetic(PK), and Pharmacodynamic(PD) Study of BIIB068 in Healthy Participants

Study Overview
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Brief Summary
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The primary objective of the study is to evaluate the safety and tolerability of single oral doses of BIIB068 in healthy participants. Secondary objectives are to characterize the single-oral-dose Pharmacokinetic (PK) of BIIB068 in healthy participants, to determine the effect of food on the single-oral-dose PK of BIIB068 in healthy participants and to examine the effect of administration of the proton pump inhibitor (PPI) esomeprazole on the single-dose PK of BIIB068 in healthy participants.

Official Title
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A Phase 1, Randomized, Blinded, Placebo-Controlled, Single-Ascending-Dose, Safety, Tolerability, Pharmacokinetic, and Pharmacodynamic Study of BIIB068, a Bruton's Tyrosine Kinase Inhibitor, in Healthy Subjects

Conditions
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Systemic Lupos Erythematosus, SLE

Intervention / Treatment
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* Drug: BIIB068
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: All male subjects must practice highly effective methods of contraception during the study and be willing and able to continue contraception and not donate sperm for at least 1 spermatogenic cycle (90 days) after administration of last dose of study treatment. All female subjects of childbearing potential must practice highly effective methods of contraception during the study and be willing and able to continue contraception for at least 1ovulatory cycle (30 days) after their last dose of study treatment. Must have a body mass index (BMI) between 18 and 32 kg/m2 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. History of severe allergic or anaphylactic reactions, or history of any allergic reactions that in the opinion of the Investigator is likely to be exacerbated by any component of the study treatment. Clinically significant abnormal laboratory test values, as determined by the Investigator, at Screening or Day-1. 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohorts 1<br>6 participants randomized (4:2) to receive a single-ascending dose (SAD) administered orally in tablet | Drug: BIIB068<br>* Administered as specified in the treatment arm.<br>* Other names: Bruton's tyrosine kinase (BTK);Drug: Placebo<br>* Administered as specified in the treatment arm<br>|
| Experimental: Cohort 2<br>6 participants randomized (4:2) to receive a SAD administered orally in tablet(s) | Drug: BIIB068<br>* Administered as specified in the treatment arm.<br>* Other names: Bruton's tyrosine kinase (BTK);Drug: Placebo<br>* Administered as specified in the treatment arm<br>|
| Experimental: Cohort 3<br>8 participants randomized (6:2) to receive a SAD administered orally in tablet(s) | Drug: BIIB068<br>* Administered as specified in the treatment arm.<br>* Other names: Bruton's tyrosine kinase (BTK);Drug: Placebo<br>* Administered as specified in the treatment arm<br>|
| Experimental: Cohort 4<br>8 participants randomized (6:2) to receive a SAD administered orally in tablet | Drug: BIIB068<br>* Administered as specified in the treatment arm.<br>* Other names: Bruton's tyrosine kinase (BTK);Drug: Placebo<br>* Administered as specified in the treatment arm<br>|
| Experimental: Cohort 5<br>8 participants randomized (6:2) to receive a SAD administered orally in tablet(s) | Drug: BIIB068<br>* Administered as specified in the treatment arm.<br>* Other names: Bruton's tyrosine kinase (BTK);Drug: Placebo<br>* Administered as specified in the treatment arm<br>|
| Experimental: Cohort 6<br>14 participants (all active) to receive a SAD administered orally in tablet(s) | Drug: BIIB068<br>* Administered as specified in the treatment arm.<br>* Other names: Bruton's tyrosine kinase (BTK);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants that experience Adverse Events (AEs) and Serious Adverse Events (SAEs) |  | Up to 9 Days Post dose | 
| Number of participants with clinically significant laboratory assessment abnormalities |  | Up to 9 Days Post dose | 
| Number of participants with clinically significant Vital sign abnormalities |  | Up to 9 Days Post dose | 
| Number of participants with clinically significant 12-lead electrocardiograms (ECGs) abnormalities |  | Up to 9 Days Post dose | 
| Number of participants with clinically significant physical examination abnormalities |  | Up to 9 Days Post dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PK Assessment - Area Under the concentration-time curve from time zero to time of the Last Measurable Concentration (AUC0-tlast) |  | Up to 48 Hours Post dose | 
| PK Assessment - Area under the concentration-time curve from time 0 to infinity (AUCinf) |  | Up to 48 Hours Post dose | 
| PK Assessment - Maximum observed concentration (Cmax) |  | Up to 48 Hours Post dose | 
| PK Assessment - Time to reach maximum observed concentration (Tmax) |  | Up to 48 Hours Post dose | 
| PK Assessment - Terminal elimination half-life (t1/2) |  | Up to 48 Hours Post dose | 
| PK Assessment - Apparent total body clearance (CL/F) |  | Up to 48 Hours Post dose | 
| PK Assessment - Apparent volume of distribution (Vz/F) |  | Up to 48 Hours Post dose | 
| PK Assessment - Amount of BIIB068 excreted in urine (Aeu) |  | Up to 48 Hours Post dose | 
| PK Assessment - Percentage (%fe) of BIIB068 excreted in urine |  | Up to 48 Hours Post dose | 
| PK Assessment - Renal clearance (CLr) |  | Up to 48 Hours Post dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Single Ascending Dose (SAD), Healthy Volunteers