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In this study, researchers will learn how the heart reacts to multiple doses of BIIB091 in healthy participants. In previous studies looking at BIIB091, researchers have found that a certain range of doses can cause changes in the electrical activity of the heart. In this study, researchers want to learn more about that activity after participants take BIIB091 at lower and higher doses for 5 days. The main objective of this study is to learn how the heart's electrical activity changes after taking BIIB091. To measure this, researchers will look at something called the QT interval corrected for heartbeat, also known as "QTc". This represents the time it takes for the heart to contract and relax. A QT interval that is too long means that the heart's electrical system is taking longer than normal to recharge between heartbeats. This could increase the risk of abnormal heartbeats that may lead to sudden death.
The main questions researchers want to answer are:
• What is the change in the participants' QTc after taking BIIB091?
Researchers will also learn more about:
This study will be done as follows:
Participants will be screened to check if they can join the study. The screening period will be up to 29 days, after which participants will check into their study research center.
Participants will be randomly assigned to be in 1 of 2 groups:
Participants will remain at their study research center for 15 days. Afterwards, there will be a follow-up visit 11 to 14 days after each participant's last dose. Each participant will be in the study for up to 57 days.
The primary objective of this study is to evaluate the effect of BIIB091 and its metabolite M23 following multiple therapeutic and supratherapeutic doses of BIIB091 on QTc intervals in healthy participants. The secondary objectives of this study are: to evaluate the effect of BIIB091 and its metabolite M23 following multiple therapeutic and supratherapeutic doses of BIIB091 on other electrocardiogram (ECG) parameters (heart rate [HR], pulse rate [PR] and QRS intervals, and ECG morphology); to demonstrate assay sensitivity of the study to detect a QTc effect using moxifloxacin as a positive control; to assess the pharmacokinetics (PK) of BIIB091 and its metabolite M23, following multiple oral dose administrations in healthy participants; to evaluate the safety and tolerability of BIIB091 in healthy participants.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| BIIB091, BIIB091-matched placebo, Moxifloxacin-matched placebo | Experimental | Participants will receive BIIB091, BIIB091-matched placebo, and moxifloxacin-matched placebo orally during the inpatient period (Days -1 to 13). |
|
| Moxifloxacin, Moxifloxacin-matched placebo, BIIB091-matched placebo | Active Comparator | Participants will receive moxifloxacin, moxifloxacin-matched placebo, and BIIB091-matched placebo orally during the inpatient period (Days -1 to 13). |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| BIIB091 | Drug | Administered as specified in the treatment arm. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline in QT Interval Corrected for Heart Rate (QTc) for BIIB091 | Baseline (Day -1) up to Day 14 | |
| Change From Baseline in QT Interval Corrected for Heart Rate (QTc) for Metabolite 23 (M23) | Baseline (Day -1) up to Day 14 |
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline in Heart Rate (ΔHR) for BIIB091 and M23 | Baseline (Day -1) up to Day 14 | |
| Change From Baseline in Pulse Rate Interval (ΔPR) for BIIB091 and M23 | Baseline (Day -1) up to Day 14 |
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Key Inclusion criteria:
Key Exclusion Criteria:
NOTE: Other protocol-defined Inclusion/Exclusion criteria may apply.
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| Name | Affiliation | Role |
|---|---|---|
| Medical Director | Biogen | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Austin Clinic PPD | Austin | Texas | 78744 | United States |
In accordance with Biogen's Clinical Trial Transparency and Data Sharing Policy on https://www.biogentrialtransparency.com/
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| ID | Term |
|---|---|
| C000722588 | BIIB091 |
| D000077266 | Moxifloxacin |
| ID | Term |
|---|---|
| D024841 | Fluoroquinolones |
| D042462 | 4-Quinolones |
| D015363 | Quinolones |
| D011804 | Quinolines |
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| Moxifloxacin | Drug | Administered as specified in the treatment arm. |
|
| BIIB091-matched Placebo | Drug | Administered as specified in the treatment arm. |
|
| Moxifloxacin-matched Placebo | Drug | Administered as specified in the treatment arm. |
|
| Change From Baseline in QRS Interval (ΔQRS) for BIIB091 and M23 | Baseline (Day -1) up to Day 14 |
| Number of Participants With Categorical Outliers for QT Interval Corrected Formula for Heart Rate (QTcF), HR, PR, and QRS for BIIB091 and M23 | From Day -1 up to Day 14 |
| Number of Participants With Treatment-Emergent Changes in ECG Morphology for BIIB091 and M23 | From Day -1 up to Day 14 |
| Time to Maximum Measured Plasma Concentration (Tmax) of BIIB091 and M23 | Pre-dose and at multiple timepoints up to Day 14 |
| Maximum Measured Plasma Concentration (Cmax) of BIIB091 and M23 | Pre-dose and at multiple timepoints up to Day 14 |
| Area Under the Plasma Concentration Versus Time Curve to 24 Hours (AUC0-24) of BIIB091 and M23 | Pre-dose and at multiple timepoints up to Day 14 |
| Area Under the Plasma Concentration Versus Time Curve to the Last Measurable Concentration (AUC0-t) of BIIB091 and M23 | Pre-dose and at multiple timepoints up to Day 14 |
| Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | From Day -1 up to end of study follow-up (up to 28 days) |
| Number of Participants With Clinically Significant Vital Signs Abnormalities | From Day -1 up to end of study follow-up (up to 28 days) |
| Number of Participants With ECG Abnormalities | From Day 1 up to Day 14 |
| Number of Participants With Clinically Significant Laboratory Assessment Abnormalities | At Days 4, 14 and follow-up (up to 28 days) |
| D006574 |
| Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |