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The primary objective of this study is to evaluate the effects of therapeutic and supratherapeutic doses of avacopan on the heart rate corrected QT interval, using Fridericia's formula (QTcF).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Cohort 1: Avacopan | Experimental | Participants will be randomized to receive multiple doses of avacopan orally twice daily (BID): 30 mg for 7 days and 100 mg for 7 days, for a total of 14 dosing days, and placebo for moxifloxacin on Days 1 and 15. |
|
| Cohort 2A: Moxifloxacin/Placebo | Active Comparator | Participants will be randomized to receive moxifloxacin 400 mg orally on Day 1, placebo for avacopan BID on Days 1 to 14, and placebo for moxifloxacin on Day 15. |
|
| Cohort 2B: Placebo/Moxifloxacin | Active Comparator | Participants will be randomized to receive placebo for moxifloxacin orally on Day 1, placebo for avacopan BID on Days 1 to 14, and moxifloxacin 400 mg orally on Day 15. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Avacopan | Drug | Administered orally. |
| |
| Moxifloxacin |
| Measure | Description | Time Frame |
|---|---|---|
| Change from Baseline in QTcF | Day -1 (baseline) and up to Day 14 |
| Measure | Description | Time Frame |
|---|---|---|
| Change from Baseline in Heart Rate (HR) | Day -1 (baseline) and Days 1, 7, and 14 | |
| Change from Baseline in Time Between P and R Wave (PR Interval) | Day -1 (baseline) and Days 1, 7, and 14 | |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| MD | Amgen | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Celerion | Tempe | Arizona | 85283 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 38973157 | Derived | Miao S, Staehr P, Tai E, Darpo B, Xue H, Armas D, Webster K, Oberoi RK. A phase I thorough QT/QTc study evaluating therapeutic and supratherapeutic doses of avacopan in healthy participants. Clin Transl Sci. 2024 Jul;17(7):e13878. doi: 10.1111/cts.13878. |
| Label | URL |
|---|---|
| AmgenTrials clinical trials website | View source |
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De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request.
Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.
Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors. If not approved, a Data Sharing Independent Review Panel will arbitrate and make the final decision. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the URL below.
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| Drug |
Administered orally. |
|
| Placebo for avacopan | Drug | Administered orally. |
|
| Placebo for moxifloxacin | Drug | Administered orally. |
|
| Change from Baseline in Complex Between Q and S Wave (QRS Interval) |
| Day -1 (baseline) and Days 1, 7, and 14 |
| Placebo-corrected Change from Baseline in HR | Day -1 (baseline) and Days 1, 7, and 14 |
| Placebo-corrected Change from Baseline in QTcF | Day -1 (baseline) and Days 1, 7, and 14 |
| Placebo-corrected Change from Baseline in PR Interval | Day -1 (baseline) and Days 1, 7, and 14 |
| Placebo-corrected Change from Baseline in QRS Interval | Day -1 (baseline) and Days 1, 7, and 14 |
| Number of Participants with Categorical Increases in QTcF from Baseline | Increases in absolute QTcF interval values from baseline >450 and ≤480 milliseconds (msec), >480 and ≤500 msec, or >500 msec, and changes from baseline of >30 and ≤60 msec, or >60 msec. | Day -1 (baseline) and Days 1, 7, and 14 |
| Number of Participants with Categorical Increases in PR Interval from Baseline | Increases in PR interval values from baseline >25% to a PR >200 msec. | Day -1 (baseline) and Days 1, 7, and 14 |
| Number of Participants with Categorical Increases in QRS Interval from Baseline | Increases in QRS interval from baseline >25% to a QRS >120 msec. | Day -1 (baseline) and Days 1, 7, and 14 |
| Number of Participants with Categorical Decreases in HR from Baseline | Decreases in HR from baseline >25% to a HR <50 beats per minute (bpm). | Day -1 (baseline) and Days 1, 7, and 14 |
| Change from Baseline in the Number of T-wave Morphology Findings | Day -1 (baseline) and Days 1, 7, and 14 |
| Change from Baseline in the Number of U-waves | Day -1 (baseline) and Days 1, 7, and 14 |
| Maximum Observed Plasma Concentration (Cmax) of Avacopan | Up to Day 14 |
| Cmax of Avacopan Metabolite M1 | Up to Day 14 |
| Time of Cmax (Tmax) of Avacopan | Up to Day 14 |
| Tmax of Avacopan Metabolite M1 | Up to Day 14 |
| Area Under the Plasma Concentration-time Curve (AUC) From Time 0 to 6 Hours (AUC0-6h) of Avacopan | Up to Hour 6 post-dose on Days 1, 7, and 14 |
| AUC0-6h of Avacopan Metabolite M1 | Up to Hour 6 post-dose on Days 1, 7, and 14 |
| AUC From Time 0 to 12 Hours (AUC0-12h) of Avacopan | Up to Hour 12 post-dose on Days 1, 7, and 14 |
| AUC0-12h of Avacopan Metabolite M1 | Up to Hour 12 post-dose on Days 1, 7, and 14 |
| ID | Term |
|---|---|
| D056648 | Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis |
| D014657 | Vasculitis |
| ID | Term |
|---|---|
| D056647 | Systemic Vasculitis |
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D017445 | Skin Diseases, Vascular |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D001327 | Autoimmune Diseases |
| D007154 | Immune System Diseases |
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| ID | Term |
|---|---|
| C000620232 | avacopan |
| D000077266 | Moxifloxacin |
| ID | Term |
|---|---|
| D024841 | Fluoroquinolones |
| D042462 | 4-Quinolones |
| D015363 | Quinolones |
| D011804 | Quinolines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
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