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| ID | Type | Description | Link |
|---|---|---|---|
| 64041575RSV1003 | Other Identifier | Janssen Research & Development, LLC |
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The primary objective of this study is to evaluate the effect of supratherapeutic exposures of ALS-008176 on the QT/ corrected QT interval (QTc) interval in healthy participants (Panel 2).
This is a two-part Phase 1 study consisting of a dose escalation part (Part 1) and a TQT part (Part 2), performed in two separate panels (Panels 1 and 2). Panel 1 will be a double blind (neither the researchers nor the participants know what treatment the participant is receiving), randomized (study medication assigned to participants by chance), placebo controlled dose escalation study in healthy participants to determine the safety, tolerability and pharmacokinetics of ALS-008176 after administration of single doses of 1500 milligrams (mg), 2500 mg and 3000 mg under fasted conditions. The final dose to be used in the Panel 2 will be determined based on the results of this dose escalation part. An interim analysis will be conducted on Panel 1 to select the dose for Panel 2. Panel 2 will be a double blind, double dummy, randomized, 3 period crossover (the same medications provided to all participants but in different sequence), placebo and positive controlled study to evaluate the effect of ALS-008176 on the QT/QTc interval in healthy participants. Participants' safety will be monitored throughout the study.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Part 1: Group 1 | Experimental | Participants will receive Treatment A (a single dose of ALS-008176 1,500 mg) or Treatment B (a single dose of placebo) under fasted conditions. |
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| Part 1: Group 2 | Experimental | Participants will receive Treatment C (a single dose of ALS-008176 2,500 mg) or Treatment D (a single dose of placebo) under fasted conditions. |
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| Part 1: Group 3 | Experimental | Participants will receive Treatment E (a single dose of ALS-008176 3,000 mg) or Treatment F (a single dose of placebo) under fasted conditions. |
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| Part 2: Sequence GHI | Experimental | Participants will receive Treatment G (a single dose of ALS-008176 3,000 mg + a single dose of moxifloxacin placebo under fasted conditions) then Treatment H (a single dose of ALS-008176 placebo + a single dose of moxifloxacin 400 mg under fasted conditions) then Treatment I (a single dose of ALS-008176 placebo + a single dose of moxifloxacin placebo under fasted conditions). There will be a washout period of at least 14 days between subsequent treatments. |
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| Part 2: Sequence HIG |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| ALS-008176 | Drug | Participants will receive a single dose of ALS-008176 orally. |
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| Measure | Description | Time Frame |
|---|---|---|
| Change from baseline in Corrected QT intervals (QTc) | Change from baseline in QTc intervals with Fredericia correction will be analyzed. | Baseline up to Day 2 |
| Measure | Description | Time Frame |
|---|---|---|
| Number of participants with adverse events as a measure of safety and tolerability | 10 to 14 days after last study drug intake | |
| Change from baseline in ECG parameters: RR interval, PR interval and QRS interval | Change from baseline in other ECG parameters (RR interval, PR interval and QRS interval) will be analyzed. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Janssen Research & Development, LLC Clinical Trial | Janssen Research & Development, LLC | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Tempe | Arizona | United States |
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| ID | Term |
|---|---|
| C000597470 | 4'-chloromethyl-2'-deoxy-3',5'-di-O-isobutyryl-2'-fluorocytidine |
| D000077266 | Moxifloxacin |
| ID | Term |
|---|---|
| D024841 | Fluoroquinolones |
| D042462 | 4-Quinolones |
| D015363 | Quinolones |
| D011804 | Quinolines |
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| Experimental |
Participants will receive Treatment H then Treatment I and then Treatment G. There will be a washout period of at least 14 days between subsequent treatments. |
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| Part 2: Sequence IGH | Experimental | Participants will receive Treatment I then Treatment G and then Treatment H. There will be a washout period of at least 14 days between subsequent treatments. |
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| Part 2: Sequence IHG | Experimental | Participants will receive Treatment I then Treatment H and then Treatment G. There will be a washout period of at least 14 days between subsequent treatments. |
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| Part 2: Sequence HGI | Experimental | Participants will receive Treatment H then Treatment G and then Treatment I. There will be a washout period of at least 14 days between subsequent treatments. |
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| Part 2: Sequence GIH | Experimental | Participants will receive Treatment G then Treatment I and then Treatment H. There will be a washout period of at least 14 days between subsequent treatments. |
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| Placebo | Drug | Matching Placebo will be administered. |
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| Moxifloxacin | Drug | Participants will receive a single dose of moxifloxacin 400 mg. |
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| Baseline up to Day 2 |
| ALS-008112 and ALS 008144 plasma concentration-effect relationship for changes in QT/QTc (Panels 1 and 2) | up to Day 15 in Panel 1; up to Day 2 in Panel 2 |
| Change from Baseline in QT/QTc interval in healthy subjects (Panel 2) | up to Day 2 |
| Maximum Observed Plasma Concentration (Cmax) | up to Day 15 in Panel 1; up to Day 2 in Panel 2 |
| Time to Reach Maximum Observed Plasma Concentration (Tmax) | up to Day 15 in Panel 1; up to Day 2 in Panel 2 |
| Area Under the Plasma Concentration-Time Curve From Time Zero to Last Quantifiable Time (AUC [0- last]) | up to Day 15 in Panel 1 |
| Area Under the Plasma Concentration-Time Curve From Time Zero to Infinite Time (AUC [0- infinity]) | up to Day 15 in Panel 1 |
| Elimination Half-Life (t1/2) | up to Day 15 in Panel 1 |
| Elimination Rate Constant (Lambda[z]) | up to Day 15 in Panel 1 |
| Plasma Concentration at 24 hours post dosing | up to Day 15 in Panel 1 |
| Area Under the Plasma Concentration-Time Curve From Time Zero to 24 Hours (AUC[0-24]) | up to Day 15 in Panel 1; up to Day 2 in Panel 2 |
| Change from baseline in Heart Rate | Change from baseline in heart rate will be analyzed. | Baseline up to Day 2 |
| Change from baseline in T wave morphology | Change from baseline in T wave morphology will be analyzed. | Baseline up to Day 2 |
| Frequency of T wave morphology changes | T-wave morphology changes will be analyzed. | up to Day 2 |
| D006574 |
| Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |