Healthy VolunteersPhase 1NCT04564612
Study of BIIB091 Formulations in Healthy Participants
A Phase 1 study testing BIIB091, Rabeprazole and Itraconazole in people with Healthy Volunteers, run by Biogen at 1 site in United Kingdom.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Healthy Volunteers
- What is being tested?
- BIIB091, Rabeprazole and Itraconazole
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 59 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 28 Sep 2020to 7 Sep 2022
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
1 site in 1 country.
About this study
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
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).
- Conditions
- Healthy Volunteers
- Being tested
- BIIB091, Rabeprazole, Itraconazole
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BIIB091Drug
Administered as specified in the treatment arm
RabeprazoleDrug
Administered as specified in the treatment arm
ItraconazoleDrug
Administered as specified in the treatment arm
| Study group | Role | What they receive |
|---|---|---|
| Part 1 | Experimental | Participants will receive single oral dose of BIIB091 on Day 1 of each study period, in fasted state, for up to 5 periods. There will be a minimum 7-day washout between Day 1 of each study period. Receives: Drug: BIIB091 |
| Part 1B | Experimental | Participants will be randomized to receive single oral or 2 oral doses for divided daily doses of BIIB091 on Day 1 of Period 1, in fasted state or single oral dose of BIIB091 on Day 1 of Period 1, in fed state. Participants will receive single oral dose of BIIB091 on Day 1 of Period 2, in fasted state. Participants will receive single or two divided oral dose(s) of BIIB091 on Day 1 of Periods 3 and 4, in fasted or fed state. There will be a minimum 7-day washout between Day 1 of each study period. Receives: Drug: BIIB091 |
| Part 2 | Experimental | Participants will receive single oral dose of BIIB091 on Day (D) 1 of Period (P) 1 in fasted/fed state; then itraconazole 100 milligram (mg) capsules (cap), orally, twice daily (BID) for 1 day (D -4) of P2, in fed state; then itraconazole 100 mg cap, orally, once daily (QD) for 2 days (D -3, -2) of P2, in fed state; then itraconazole 100 mg cap, orally, QD for 1 day (D -1) of P2, in fasted/fed state; then combination of itraconazole 100 mg cap, orally and BIIB091, orally on 5th day (D 1) of P2, in fasted/fed state; then itraconazole 100 mg cap, orally on 6th day (D 2) of P2, in fed state; then rabeprazole 20 mg tablets (tab), orally, BID for 3 days (D -3, -2, and -1) of P3 in fed state; then combination of rabeprazole 20 mg tab, orally and BIIB091, orally, on 4th day (D 1) of P3 in fasted/fed state. Minimum 7-day washout between dose of BIIB091 in P1 and 1st dose of itraconazole in P2; minimum 10-day washout between final dose of itraconazole in P2 and 1st dose of rabeprazole in P3. Receives: Drug: BIIB091; Drug: Rabeprazole; Drug: Itraconazole |
| Part 3 | Experimental | Participants will receive BIIB091, orally, QD or BID for at least 7 days in fasted or fed state. Receives: Drug: BIIB091 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Parts 1 and 1B: Time Prior to the First Measurable Concentration (Tlag) of BIIB091
Measured: 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
Measured: 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
Measured: 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
Measured: Parts 1 and 1B: 12 hours post-dose (Day 1)
Parts 1 and 1B: Plasma Concentration at 24 Hours (C24h) of BIIB091
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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)
Measured: 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)
Measured: 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)
Measured: 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
Measured: 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
Measured: Part 2: Up to Day 5
Part 2: Frel Cmax of BIIB091 Dosed With and Without Cytochrome P450 (CYP) 3A4 Inhibitor
Measured: Part 2: Up to Day 5
Part 2: Frel AUC(0-last) of BIIB091 Dosed With and Without CYP3A4 Inhibitor
Measured: Part 2: Up to Day 5
Part 2: Frel AUC(0-inf) of BIIB091 Dosed With and Without CYP3A4 Inhibitor
Measured: Part 2: Up to Day 5
Part 3: Concentration at the End of the Dosing Interval (Ctrough) of BIIB091
Measured: Part 3: Up to Day 14
Part 3: Area Under Curve Observed at the End of the Dosing Interval (AUCtau) of BIIB091
Measured: Part 3: Up to Day 14
Part 3: Plasma Concentration Observed at the End of the Dosing Interval (Ctau) of BIIB091
Measured: Part 3: Up to Day 14
Part 3: Minimum Observed Concentration (Cmin) of BIIB091
Measured: Part 3: Up to Day 14
Part 3: Average Concentration (Cave) of BIIB091
Measured: Part 3: Up to Day 14
Part 3: Peak to Trough Fluctuation
The formula used will be (Cmax-Cmin)/average concentration (Cavg) × 100.
Measured: Part 3: Up to Day 14
Part 3: Accumulation Ratio Based on Cmax/Cmax Single Dose (AR Cmax)
Measured: Part 3: Up to Day 14
Part 3: Accumulation Ratio Based on AUCtau/AUCtau Single Dose (AR AUCtau)
Measured: Part 3: Up to Day 14
Part 3: Total Body Clearance Calculated Using AUCtau After Repeated Extravascular Administration Where F is Unknown (CL/Ftau)
Measured: 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)
Measured: Part 3: Up to Day 14
Secondary outcomes (20)
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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
Measured: 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
Parameter will be evaluated for the fed vs fasted comparison and the alternative meal composition comparison in Part 1B.
Measured: Parts 1B and 2: Up to Day 5
Parts 1B and 2: Time of Maximum Observed Concentration (Tmax) of BIIB091
Parameter will be evaluated for the fed vs fasted comparison and the alternative meal composition comparison in Part 1B.
Measured: Parts 1B and 2: Up to Day 5
Parts 1B and 2: Maximum Observed Concentration (Cmax) of BIIB091
Parameter will be evaluated for the fed vs fasted comparison and the alternative meal composition comparison in Part 1B.
Measured: Parts 1B and 2: Up to Day 5
Parts 1B and 2: Plasma Concentration at 12 Hours (C12h) of BIIB091
Parameter will be evaluated for the fed vs fasted comparison and the alternative meal composition comparison in Part 1B.
Measured: Parts 1B and 2: 12 hours post-dose (Day 1)
Parts 1B and 2: Plasma Concentration at 24 Hours (C24h) of BIIB091
Parameter will be evaluated for the fed vs fasted comparison and the alternative meal composition comparison in Part 1B.
Measured: Parts 1B and 2: 24 hours post-dose (Day 2)
Parts 1B and 2: Area Under the Curve from Time 0 to 12 Hours Post-Dose [AUC(0-12h)] of BIIB091
Parameter will be evaluated for the fed vs fasted comparison and the alternative meal composition comparison in Part 1B.
Measured: Parts 1B and 2: Up to 12 hours post-dose (Day 1)
Parts 1B and 2: Area Under the Curve from Time 0 to 24 Hours Post-Dose [AUC(0-24h)] of BIIB091
Parameter will be evaluated for the fed vs fasted comparison and the alternative meal composition comparison in Part 1B.
Measured: Parts 1B and 2: Up to 24 hours post-dose (Day 2)
Parts 1B and 2: Area Under the Curve from Time 0 to the Time of Last Measurable Concentration [AUC(0-last)] of BIIB091
Parameter will be evaluated for the fed vs fasted comparison and the alternative meal composition comparison in Part 1B.
Measured: Parts 1B and 2: Up to Day 5
Parts 1B and 2: Area Under the Curve from Time 0 Extrapolated to Infinity [AUC(0-inf)] of BIIB091
Parameter will be evaluated for the fed vs fasted comparison and the alternative meal composition comparison in Part 1B.
Measured: Parts 1B and 2: Post-dose at multiple time points up to Day 5
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
Parameter will be evaluated for the fed vs fasted comparison and the alternative meal composition comparison in Part 1B.
Measured: Parts 1B and 2: Up to Day 5
Parts 1B and 2: Terminal Elimination Half-Life (T1/2) of BIIB091
Parameter will be evaluated for the fed vs fasted comparison and the alternative meal composition comparison in Part 1B.
Measured: Parts 1B and 2: Up to Day 5
Parts 1B and 2: First Order Rate Constant Associated with the Terminal (Log-Linear) Portion of the Curve (Lambda-z) of BIIB091
Parameter will be evaluated for the fed vs fasted comparison and the alternative meal composition comparison in Part 1B.
Measured: Parts 1B and 2: Up to Day 5
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)
Parameter will be evaluated for the fed vs fasted comparison and the alternative meal composition comparison in Part 1B.
Measured: Parts 1B and 2: Up to Day 5
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)
Parameter will be evaluated for the fed vs fasted comparison and the alternative meal composition comparison in Part 1B.
Measured: Parts 1B and 2: Up to Day 5
Part 1B: Relative Bioavailability of BIIB091 Based on AUC(0-24h) [Frel AUC(0-24h)]
Measured: Part 1B: Up to Day 5
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Sep 2020
- Study start28 Sep 2020
- Primary completion7 Sep 2022
- Study completion7 Sep 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Healthy VolunteersStudies of the same condition, open and under way.
- More trials run by BiogenThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 59 participants (actual)
Sponsor and investigators
- Lead sponsor
- Biogen
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Director, Study director, Biogen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04564612
- Sponsor's protocol ID
- 257HV105
- Other IDs
- 2020-000682-16
- Status last verified
- Apr 2023
- First submitted
- 21 Sep 2020
- Last updated
- 18 Apr 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: In accordance with Biogen's Clinical Trial Transparency and Data Sharing Policy on https://www.biogentrialtransparency.com/
Study at a glance
From the registry record, last updated by the sponsor on 18 Apr 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT04564612
- Acronym / sponsor ID
- 257HV105
- Conditions
- Healthy Volunteers
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 59 participants (actual)
- Lead sponsor
- BiogenIndustry (pharma, biotech, devices)
- Study start
- 28 Sep 2020 (actual)
- Primary completion
- 7 Sep 2022 (actual)
- Study completion
- 7 Sep 2022 (actual)
- First posted
- 25 Sep 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Part 1 | Experimental | Drug: BIIB091Participants will receive single oral dose of BIIB091 on Day 1 of each study period, in fasted state, for up to 5 periods. There will be a minimum 7-day washout between Day 1 of each study period. |
| Part 1B | Experimental | Drug: BIIB091Participants will be randomized to receive single oral or 2 oral doses for divided daily doses of BIIB091 on Day 1 of Period 1, in fasted state or single oral dose of BIIB091 on Day 1 of Period 1, in fed state. Participants will receive single oral dose of BIIB091 on Day 1 of Period 2, in fasted state. Participants will receive single or two divided oral dose(s) of BIIB091 on Day 1 of Periods 3 and 4, in fasted or fed state. There will be a minimum 7-day washout between Day 1 of each study period. |
| Part 2 | Experimental | Drug: BIIB091, Drug: Rabeprazole, Drug: ItraconazoleParticipants will receive single oral dose of BIIB091 on Day (D) 1 of Period (P) 1 in fasted/fed state; then itraconazole 100 milligram (mg) capsules (cap), orally, twice daily (BID) for 1 day (D -4) of P2, in fed state; then itraconazole 100 mg cap, orally, once daily (QD) for 2 days (D -3, -2) of P2, in fed state; then itraconazole 100 mg cap, orally, QD for 1 day (D -1) of P2, in fasted/fed state; then combination of itraconazole 100 mg cap, orally and BIIB091, orally on 5th day (D 1) of P2, in fasted/fed state; then itraconazole 100 mg cap, orally on 6th day (D 2) of P2, in fed state; then rabeprazole 20 mg tablets (tab), orally, BID for 3 days (D -3, -2, and -1) of P3 in fed state; then combination of rabeprazole 20 mg tab, orally and BIIB091, orally, on 4th day (D 1) of P3 in fasted/fed state. Minimum 7-day washout between dose of BIIB091 in P1 and 1st dose of itraconazole in P2; minimum 10-day washout between final dose of itraconazole in P2 and 1st dose of rabeprazole in P3. |
| Part 3 | Experimental | Drug: BIIB091Participants will receive BIIB091, orally, QD or BID for at least 7 days in fasted or fed state. |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (3 listed)
- 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 (14 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BIIB091Administered as specified in the treatment arm | Drug | Part 1, Part 1B, Part 2, Part 3 |
| RabeprazoleAdministered as specified in the treatment arm | Drug | Part 2 |
| ItraconazoleAdministered as specified in the treatment arm | Drug | Part 2 |
Primary outcome
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
Time frame: Part 3: Up to Day 14
The formula used will be (Cmax-Cmin)/average concentration (Cavg) × 100.
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
20 secondary outcomes
Parts 1 and 1B: Frel Cmax of BIIB091
Time frame: Part 1: Up to Day 4; Part 1B: Up to Day 5
Parts 1 and 1B: Frel AUC(0-last) of BIIB091
Time frame: Part 1: Up to Day 4; Part 1B: Up to Day 5
Parts 1 and 1B: Frel AUC(0-inf) of BIIB091
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)
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
Time frame: Parts 1B and 2: Up to Day 5
Parts 1B and 2: Time of Maximum Observed Concentration (Tmax) of BIIB091
Time frame: Parts 1B and 2: Up to Day 5
Parts 1B and 2: Maximum Observed Concentration (Cmax) of BIIB091
Time frame: Parts 1B and 2: Up to Day 5
Parts 1B and 2: Plasma Concentration at 12 Hours (C12h) of BIIB091
Time frame: Parts 1B and 2: 12 hours post-dose (Day 1)
Parts 1B and 2: Plasma Concentration at 24 Hours (C24h) of BIIB091
Time frame: Parts 1B and 2: 24 hours post-dose (Day 2)
Parts 1B and 2: Area Under the Curve from Time 0 to 12 Hours Post-Dose [AUC(0-12h)] of BIIB091
Time frame: Parts 1B and 2: Up to 12 hours post-dose (Day 1)
Parts 1B and 2: Area Under the Curve from Time 0 to 24 Hours Post-Dose [AUC(0-24h)] of BIIB091
Time frame: Parts 1B and 2: Up to 24 hours post-dose (Day 2)
Parts 1B and 2: Area Under the Curve from Time 0 to the Time of Last Measurable Concentration [AUC(0-last)] of BIIB091
Time frame: Parts 1B and 2: Up to Day 5
Parts 1B and 2: Area Under the Curve from Time 0 Extrapolated to Infinity [AUC(0-inf)] of BIIB091
Time frame: Parts 1B and 2: Post-dose at multiple time points up to Day 5
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
Time frame: Parts 1B and 2: Up to Day 5
Parts 1B and 2: Terminal Elimination Half-Life (T1/2) of BIIB091
Time frame: Parts 1B and 2: Up to Day 5
Parts 1B and 2: First Order Rate Constant Associated with the Terminal (Log-Linear) Portion of the Curve (Lambda-z) of BIIB091
Time frame: Parts 1B and 2: Up to Day 5
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)
Time frame: Parts 1B and 2: Up to Day 5
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)
Time frame: Parts 1B and 2: Up to Day 5
Part 1B: Relative Bioavailability of BIIB091 Based on AUC(0-24h) [Frel AUC(0-24h)]
Time frame: Part 1B: Up to Day 5
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Apr 2023.
- Individual participant dataSharing planned: Yes. In accordance with Biogen's Clinical Trial Transparency and Data Sharing Policy on https://www.biogentrialtransparency.com/
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Medical Director study director
Biogen
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing BIIB091, Rabeprazole and Itraconazole in people with Healthy Volunteers, run by Biogen at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 18 Apr 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). The study lists 30 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Apr 2023.