Study of BIIB091 Formulations in Healthy Participants

Biogen59 enrolled

Overview

The primary objectives of this study are: to evaluate the pharmacokinetic (PK) profiles of BIIB091 modified release (MR) formulations in healthy participants after single dose administration in the fasted state (Part 1); to evaluate the PK profile of the BIIB091 immediate release (IR) tablet formulation in healthy participants after single dose administration (Part 1B); to determine the relative bioavailability of single doses of the selected BIIB091 regimen in healthy participants taking a proton pump inhibitor (PPI) compared to healthy participants not taking a PPI, to determine the relative bioavailability of single doses of the selected BIIB091 regimen in healthy participants taking a cytochrome P450 (CYP)3A4 inhibitor compared to healthy participants not taking a CYP3A4 inhibitor (Part 2); to evaluate the PK of the selected BIIB091 regimen in healthy participants after multiple dose administration (Part 3). The secondary objectives of this study are: to determine the relative bioavailability of a single dose of the BIIB091 MR formulations compared to that of the IR drug in capsule (DiC) reference formulation in healthy participants in the fasted state, to assess the safety and tolerability of single doses of BIIB091 when administered as MR formulations in healthy participants in the fasted state (Part 1); to determine the PK of a single dose of the BIIB091 IR tablet formulation in the fed and fasted state in healthy participants, to evaluate the PK profiles of the BIIB091 IR tablet formulation in healthy participants after administration of divided total daily doses over a 24 hour period in the fasted or fed state, to determine the relative bioavailability of a single dose or divided dose of the BIIB091 IR tablet formulation compared to that of the IR DiC reference formulation in healthy participants in the fasted state, to determine the PK of a single or divided dose of the BIIB091 IR tablet formulation administered with an alternative meal composition in healthy participants, to assess the safety and tolerability of a single or divided dose of BIIB091 when administered as the IR tablet formulation and IR DiC reference formulation in healthy participants in fed or fasted state (Part 1B); to confirm the PK profiles of the selected BIIB091 regimen in healthy participants after single dose administration, and to establish a reference exposure for the assessment of drug interaction, to assess the safety and tolerability of single doses of BIIB091 when administered as the selected BIIB091 regimen in healthy participants taking a PPI, to assess the safety and tolerability of single doses of BIIB091 when administered as the selected BIIB091 regimen in healthy participants taking a CYP3A4 inhibitor (Part 2); to assess the safety and tolerability of multiple doses of BIIB091 when administered as the selected BIIB091 regimen in healthy participants (Part 3).

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Interventions

BIIB091DRUG

Administered as specified in the treatment arm

RabeprazoleDRUG

Administered as specified in the treatment arm

ItraconazoleDRUG

Administered as specified in the treatment arm

Eligibility

Sex: ALLMin age: 18 YearsMax age: 55 YearsHealthy volunteers:

Medical Language ↔ Plain English

Key Inclusion Criteria: * Have a body mass index (BMI) between 18.0 and 30.0 kilograms per meter square (kg/m\^2), inclusive, and a body weight of at least 50 kilogram (kg), as measured at screening. * Must be in good health as determined by the Investigator, based on medical history and screening evaluations. * A negative test for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) according to local guidelines, at screening and admission or prior to admission. Key Exclusion Criteria: * History of any clinically significant cardiac, endocrine, GI, hematologic, hepatic, immunologic, metabolic, urologic, pulmonary, neurologic, dermatologic, psychiatric, or renal disease, or other major disease, as determined by the Investigator. * Clinically significant 12-lead ECG abnormalities at screening and prior to first dose, including confirmed demonstration of QT interval corrected for heart rate using Fridericia's formula (QTcF) \>450 milliseconds (msec), QRS \>120 msec, PR \>220 msec, or heart rate \<50 beats per minute (bpm) based on the average of triplicate measurements, early repolarization, or any other clinically significant 12-lead ECG abnormalities as determined by the Investigator. * History of torsades de pointes or additional risk factors for torsades de pointes (e.g. heart failure, hypokalemia, family history of long QT syndrome, or any medications known to prolong QT interval administered within 5.5 half-lives prior to screening), in the opinion of the Investigator. * Receipt of any vaccination within 30 days prior to screening, or plans to receive the same any time from screening through to 30 days after the last study visit. However, non-live coronavirus disease 2019 (COVID-19) vaccination will be permitted 21 days or more prior to the first dose of BIIB091, as per local regulation and Investigator discretion. * Evidence of current SARS-CoV-2 infection within the past 4 weeks at screening, between screening and admission, or at admission, including but not limited to any of the following symptoms: fever (temperature more than {\>} 37.5 degree Celsius {°C}), new and persistent cough, breathlessness, or loss of taste or smell as per the judgement of the Investigator. * Contact with an individual with COVID-19 infection in the past 14 days at screening, between screening and admission, or at admission. * Presence or history of chronic, recurrent, or serious infection, as determined by the Investigator, within 90 days prior to screening or between screening and admission. * Clinically significant abnormal laboratory test values, as determined by the Investigator, at screening. * Current enrollment or plan to enroll in any other drug, biological, device, or clinical study, or treatment with an investigational drug or approved therapy for investigational use within 90 days prior to Day 1, or 5 half-lives of the drug or therapy, whichever is longer. * Use of CYP3A4 inducers or inhibitors (including hormonal contraceptives as applicable) within 14 days before the first dose of study medication. Use of organic anion transporting polypeptide 1 (OATP1) B1 and B3 substrates in the 14 days before first dose of study medication. * Chronic use of immunosuppressive or immunomodulatory drugs within 6 months prior to admission. (Recent acute use of immunosuppressants should be discussed with Sponsor.) * Consumption of any product containing grapefruit, pomelos, or Seville oranges within 14 days of admission and an unwillingness to refrain from such products during study participation. * Participants who have previously been enrolled in this study. NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Locations (1)

Research Site

Nottingham, United Kingdom

Outcomes

Primary Outcomes

Parts 1 and 1B: Time Prior to the First Measurable Concentration (Tlag) of BIIB091

Time frame: Part 1: Up to Day 4; Part 1B: Up to Day 5

Parts 1, 1B and 3: Time of Maximum Observed Concentration (Tmax) of BIIB091

Time frame: Part 1: Up to Day 4; Part 1B: Up to Day 5; Part 3: Up to Day 14

Parts 1, 1B and 3: Maximum Observed Concentration (Cmax) of BIIB091

Time frame: Part 1: Up to Day 4; Part 1B: Up to Day 5; Part 3: Up to Day 14

Parts 1 and 1B: Plasma Concentration at 12 Hours (C12h) of BIIB091

Time frame: Parts 1 and 1B: 12 hours post-dose (Day 1)

Parts 1 and 1B: Plasma Concentration at 24 Hours (C24h) of BIIB091

Time frame: Parts 1 and 1B: 24 hours post-dose (Day 2)

Parts 1 and 1B: Area Under the Curve from Time 0 to 12 Hours Post-Dose [AUC(0-12h)] of BIIB091

Time frame: Parts 1 and 1B: Up to 12 hours post-dose (Day 1)

Parts 1 and 1B: Area Under the Curve from Time 0 to 24 Hours Post-Dose [AUC(0-24h)] of BIIB091

Time frame: Parts 1 and 1B: Up to 24 hours post-dose (Day 2)

Parts 1 and 1B: Area Under the Curve from Time 0 to the Time of Last Measurable Concentration [AUC(0-last)] of BIIB091

Time frame: Part 1: Up to Day 4; Part 1B: Up to Day 5

Parts 1, 1B and 3: Area Under the Curve from Time 0 Extrapolated to Infinity [AUC(0-inf)] of BIIB091

Time frame: Part 1: Post-dose at multiple time points up to Day 4; Part 1B: Post-dose at multiple time points up to Day 5; Part 3: Post-dose at multiple time points up to Day 14

Parts 1 and 1B: Area Under the Curve from Time of the Last Measurable Concentration to Infinity as a Percentage of the Area Under the Curve Extrapolated to Infinity (AUC%extrap) of BIIB091

Time frame: Part 1: Up to Day 4; Part 1B: Up to Day 5

Parts 1, 1B and 3: Terminal Elimination Half-Life (T1/2) of BIIB091

Time frame: Part 1: Up to Day 4; Part 1B: Up to Day 5; Part 3: Up to Day 14

Parts 1, 1B and 3: First Order Rate Constant Associated with the Terminal (Log-Linear) Portion of the Curve (Lambda-z) of BIIB091

Time frame: Part 1: Up to Day 4; Part 1B: Up to Day 5; Part 3: Up to Day 14

Parts 1 and 1B: Total Body Clearance of BIIB091 Calculated After a Single Extravascular Administration Where Fraction of Dose Bioavailable (F) is Unknown (CL/F)

Time frame: Part 1: Up to Day 4; Part 1B: Up to Day 5

Parts 1 and 1B: Apparent Volume of Distribution of BIIB091 Based on the Terminal Phase Calculated Using AUC(0-inf) After a Single Extravascular Administration Where F is Unknown (Vd/F)

Time frame: Part 1: Up to Day 4; Part 1B: Up to Day 5

Part 2: Relative Bioavailability of BIIB091 Based on Cmax (Frel Cmax) of BIIB091 Dosed With and Without Proton Pump Inhibitor (PPI)

Time frame: Part 2: Up to Day 5

Part 2: Relative Bioavailability of BIIB091 Based on AUC(0-last) [Frel AUC(0-last)] of BIIB091 Dosed With and Without PPI

Time frame: Part 2: Up to Day 5

Part 2: Relative Bioavailability of BIIB091 Based on AUC(0-inf) [Frel AUC(0-inf)] of BIIB091 Dosed With and Without PPI

Time frame: Part 2: Up to Day 5

Part 2: Frel Cmax of BIIB091 Dosed With and Without Cytochrome P450 (CYP) 3A4 Inhibitor

Time frame: Part 2: Up to Day 5

Part 2: Frel AUC(0-last) of BIIB091 Dosed With and Without CYP3A4 Inhibitor

Time frame: Part 2: Up to Day 5

Part 2: Frel AUC(0-inf) of BIIB091 Dosed With and Without CYP3A4 Inhibitor

Time frame: Part 2: Up to Day 5

Part 3: Concentration at the End of the Dosing Interval (Ctrough) of BIIB091

Time frame: Part 3: Up to Day 14

Part 3: Area Under Curve Observed at the End of the Dosing Interval (AUCtau) of BIIB091

Time frame: Part 3: Up to Day 14

Part 3: Plasma Concentration Observed at the End of the Dosing Interval (Ctau) of BIIB091

Time frame: Part 3: Up to Day 14

Part 3: Minimum Observed Concentration (Cmin) of BIIB091

Time frame: Part 3: Up to Day 14

Part 3: Average Concentration (Cave) of BIIB091

Time frame: Part 3: Up to Day 14

Part 3: Peak to Trough Fluctuation

The formula used will be (Cmax-Cmin)/average concentration (Cavg) × 100.

Time frame: Part 3: Up to Day 14

Part 3: Accumulation Ratio Based on Cmax/Cmax Single Dose (AR Cmax)

Time frame: Part 3: Up to Day 14

Part 3: Accumulation Ratio Based on AUCtau/AUCtau Single Dose (AR AUCtau)

Time frame: Part 3: Up to Day 14

Part 3: Total Body Clearance Calculated Using AUCtau After Repeated Extravascular Administration Where F is Unknown (CL/Ftau)

Time frame: Part 3: Up to Day 14

Part 3: Apparent Volume of Distribution Based on the Terminal Phase Calculated Using AUCtau After Extravascular Administration Where F is Unknown (Vd/Ftau)

Time frame: Part 3: Up to Day 14

Secondary Outcomes

Parts 1 and 1B: Frel Cmax of BIIB091

Parameter will be evaluated for the fed versus (vs) fasted comparison and the alternative meal composition comparison.

Time frame: Part 1: Up to Day 4; Part 1B: Up to Day 5

Parts 1 and 1B: Frel AUC(0-last) of BIIB091

Parameter will be evaluated for the fed vs fasted comparison and the alternative meal composition comparison.

Time frame: Part 1: Up to Day 4; Part 1B: Up to Day 5

Parts 1 and 1B: Frel AUC(0-inf) of BIIB091

Parameter will be evaluated for the fed vs fasted comparison and the alternative meal composition comparison.

Time frame: Part 1: Up to Day 4; Part 1B: Up to Day 5

Parts 1, 1B, 2 and 3: Number of Participants with Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)

An adverse event (AE) is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An SAE is any untoward medical occurrence that at any dose results in death, places the participant at immediate risk of death, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, results in a congenital anomaly/birth defect or is a medically important event.

Time frame: From Signing of Informed Consent Form (ICF) Until Follow-up Phone Call (Parts 1 and 1B: Up to 15 weeks; Part 2: Up to 10 weeks; Part 3: Up to 7 weeks)

Parts 1, 1B, 2 and 3: Number of Participants with Electrocardiogram (ECG) Abnormalities as Assessed by 12-Lead ECG Measurements

Time frame: Part 1: Up to Day 4; Parts 1B and 2: Up to Day 5; Part 3: Up to Day 14

Parts 1B and 2: Time Prior to the First Measurable Concentration (Tlag) of BIIB091