Clinical trial NCT04564612: Study of BIIB091 Formulations in Healthy Participants
Official title: An Open-Label, Pharmacokinetic Study to Evaluate the Pharmacokinetics and Relative Bioavailability of BIIB091 Formulations and to Assess the Impact of Food, a Proton Pump Inhibitor and CYP3A4 Inhibitor on BIIB091 Exposure Using the Selected Formulation in Healthy Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteers
Lead sponsor: Biogen
Sponsor class: INDUSTRY
First posted: 2020-09-25
Enrollment: 59
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: 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).


Eligibility criteria: 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.

Primary outcomes:
measure: Parts 1 and 1B: Time Prior to the First Measurable Concentration (Tlag) of BIIB091
timeFrame: Part 1: Up to Day 4; Part 1B: Up to Day 5
measure: Parts 1, 1B and 3: Time of Maximum Observed Concentration (Tmax) of BIIB091
timeFrame: Part 1: Up to Day 4; Part 1B: Up to Day 5; Part 3: Up to Day 14
measure: Parts 1, 1B and 3: Maximum Observed Concentration (Cmax) of BIIB091
timeFrame: Part 1: Up to Day 4; Part 1B: Up to Day 5; Part 3: Up to Day 14
measure: Parts 1 and 1B: Plasma Concentration at 12 Hours (C12h) of BIIB091
timeFrame: Parts 1 and 1B: 12 hours post-dose (Day 1)
measure: Parts 1 and 1B: Plasma Concentration at 24 Hours (C24h) of BIIB091
timeFrame: Parts 1 and 1B: 24 hours post-dose (Day 2)
measure: Parts 1 and 1B: Area Under the Curve from Time 0 to 12 Hours Post-Dose [AUC(0-12h)] of BIIB091
timeFrame: Parts 1 and 1B: Up to 12 hours post-dose (Day 1)
measure: Parts 1 and 1B: Area Under the Curve from Time 0 to 24 Hours Post-Dose [AUC(0-24h)] of BIIB091
timeFrame: Parts 1 and 1B: Up to 24 hours post-dose (Day 2)
measure: Parts 1 and 1B: Area Under the Curve from Time 0 to the Time of Last Measurable Concentration [AUC(0-last)] of BIIB091
timeFrame: Part 1: Up to Day 4; Part 1B: Up to Day 5
measure: Parts 1, 1B and 3: Area Under the Curve from Time 0 Extrapolated to Infinity [AUC(0-inf)] of BIIB091
timeFrame: 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
measure: 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
timeFrame: Part 1: Up to Day 4; Part 1B: Up to Day 5
measure: Parts 1, 1B and 3: Terminal Elimination Half-Life (T1/2) of BIIB091
timeFrame: Part 1: Up to Day 4; Part 1B: Up to Day 5; Part 3: Up to Day 14
measure: Parts 1, 1B and 3: First Order Rate Constant Associated with the Terminal (Log-Linear) Portion of the Curve (Lambda-z) of BIIB091
timeFrame: Part 1: Up to Day 4; Part 1B: Up to Day 5; Part 3: Up to Day 14
measure: 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)
timeFrame: Part 1: Up to Day 4; Part 1B: Up to Day 5
measure: 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)
timeFrame: Part 1: Up to Day 4; Part 1B: Up to Day 5
measure: Part 2: Relative Bioavailability of BIIB091 Based on Cmax (Frel Cmax) of BIIB091 Dosed With and Without Proton Pump Inhibitor (PPI)
timeFrame: Part 2: Up to Day 5
measure: Part 2: Relative Bioavailability of BIIB091 Based on AUC(0-last) [Frel AUC(0-last)] of BIIB091 Dosed With and Without PPI
timeFrame: Part 2: Up to Day 5
measure: Part 2: Relative Bioavailability of BIIB091 Based on AUC(0-inf) [Frel AUC(0-inf)] of BIIB091 Dosed With and Without PPI
timeFrame: Part 2: Up to Day 5
measure: Part 2: Frel Cmax of BIIB091 Dosed With and Without Cytochrome P450 (CYP) 3A4 Inhibitor
timeFrame: Part 2: Up to Day 5
measure: Part 2: Frel AUC(0-last) of BIIB091 Dosed With and Without CYP3A4 Inhibitor
timeFrame: Part 2: Up to Day 5
measure: Part 2: Frel AUC(0-inf) of BIIB091 Dosed With and Without CYP3A4 Inhibitor
timeFrame: Part 2: Up to Day 5
measure: Part 3: Concentration at the End of the Dosing Interval (Ctrough) of BIIB091
timeFrame: Part 3: Up to Day 14
measure: Part 3: Area Under Curve Observed at the End of the Dosing Interval (AUCtau) of BIIB091
timeFrame: Part 3: Up to Day 14
measure: Part 3: Plasma Concentration Observed at the End of the Dosing Interval (Ctau) of BIIB091
timeFrame: Part 3: Up to Day 14
measure: Part 3: Minimum Observed Concentration (Cmin) of BIIB091
timeFrame: Part 3: Up to Day 14
measure: Part 3: Average Concentration (Cave) of BIIB091
timeFrame: Part 3: Up to Day 14
measure: Part 3: Peak to Trough Fluctuation
timeFrame: Part 3: Up to Day 14
measure: Part 3: Accumulation Ratio Based on Cmax/Cmax Single Dose (AR Cmax)
timeFrame: Part 3: Up to Day 14
measure: Part 3: Accumulation Ratio Based on AUCtau/AUCtau Single Dose (AR AUCtau)
timeFrame: Part 3: Up to Day 14
measure: Part 3: Total Body Clearance Calculated Using AUCtau After Repeated Extravascular Administration Where F is Unknown (CL/Ftau)
timeFrame: Part 3: Up to Day 14
measure: Part 3: Apparent Volume of Distribution Based on the Terminal Phase Calculated Using AUCtau After Extravascular Administration Where F is Unknown (Vd/Ftau)
timeFrame: Part 3: Up to Day 14
Secondary outcomes:
measure: Parts 1 and 1B: Frel Cmax of BIIB091
timeFrame: Part 1: Up to Day 4; Part 1B: Up to Day 5
measure: Parts 1 and 1B: Frel AUC(0-last) of BIIB091
timeFrame: Part 1: Up to Day 4; Part 1B: Up to Day 5
measure: Parts 1 and 1B: Frel AUC(0-inf) of BIIB091
timeFrame: Part 1: Up to Day 4; Part 1B: Up to Day 5
measure: Parts 1, 1B, 2 and 3: Number of Participants with Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
timeFrame: 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)
measure: Parts 1, 1B, 2 and 3: Number of Participants with Electrocardiogram (ECG) Abnormalities as Assessed by 12-Lead ECG Measurements
timeFrame: Part 1: Up to Day 4; Parts 1B and 2: Up to Day 5; Part 3: Up to Day 14
measure: Parts 1B and 2: Time Prior to the First Measurable Concentration (Tlag) of BIIB091
timeFrame: Parts 1B and 2: Up to Day 5
measure: Parts 1B and 2: Time of Maximum Observed Concentration (Tmax) of BIIB091
timeFrame: Parts 1B and 2: Up to Day 5
measure: Parts 1B and 2: Maximum Observed Concentration (Cmax) of BIIB091
timeFrame: Parts 1B and 2: Up to Day 5
measure: Parts 1B and 2: Plasma Concentration at 12 Hours (C12h) of BIIB091
timeFrame: Parts 1B and 2: 12 hours post-dose (Day 1)
measure: Parts 1B and 2: Plasma Concentration at 24 Hours (C24h) of BIIB091
timeFrame: Parts 1B and 2: 24 hours post-dose (Day 2)
measure: Parts 1B and 2: Area Under the Curve from Time 0 to 12 Hours Post-Dose [AUC(0-12h)] of BIIB091
timeFrame: Parts 1B and 2: Up to 12 hours post-dose (Day 1)
measure: Parts 1B and 2: Area Under the Curve from Time 0 to 24 Hours Post-Dose [AUC(0-24h)] of BIIB091
timeFrame: Parts 1B and 2: Up to 24 hours post-dose (Day 2)
measure: Parts 1B and 2: Area Under the Curve from Time 0 to the Time of Last Measurable Concentration [AUC(0-last)] of BIIB091
timeFrame: Parts 1B and 2: Up to Day 5
measure: Parts 1B and 2: Area Under the Curve from Time 0 Extrapolated to Infinity [AUC(0-inf)] of BIIB091
timeFrame: Parts 1B and 2: Post-dose at multiple time points up to Day 5
measure: Parts 1B and 2: 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
timeFrame: Parts 1B and 2: Up to Day 5
measure: Parts 1B and 2: Terminal Elimination Half-Life (T1/2) of BIIB091
timeFrame: Parts 1B and 2: Up to Day 5
measure: Parts 1B and 2: First Order Rate Constant Associated with the Terminal (Log-Linear) Portion of the Curve (Lambda-z) of BIIB091
timeFrame: Parts 1B and 2: Up to Day 5
measure: Parts 1B and 2: Total Body Clearance of BIIB091 Calculated After a Single Extravascular Administration Where Fraction of Dose Bioavailable (F) is Unknown (CL/F)
timeFrame: Parts 1B and 2: Up to Day 5
measure: Parts 1B and 2: 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)
timeFrame: Parts 1B and 2: Up to Day 5
measure: Part 1B: Relative Bioavailability of BIIB091 Based on AUC(0-24h) [Frel AUC(0-24h)]
timeFrame: Part 1B: Up to Day 5
Other outcomes:
Locations:
city: Nottingham
country: United Kingdom
facility: Research Site
Study officials:
affiliation: Biogen
name: Medical Director
role: STUDY_DIRECTOR
References: