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This study is to evaluate the effects of single therapeutic and supratherapeutic oral doses of ACP-196 on the heart rate-corrected QT interval using Fridericia's formula (QTcF).
This is a single-dose, randomized, double-blind, double-dummy, placebo- and positive-controlled, 4-period, balanced crossover study under fasting conditions. Participants will be randomized to 1 of 4 treatment sequences: ABCD, BDAC, CADB, or DCBA. On 4 different occasions (4 periods), each participant will receive Treatment A (a single therapeutic oral dose of 100 mg ACP-196), Treatment B (a single supratherapeutic oral dose of 400 mg ACP-196), Treatment C (a single oral dose of 400 mg moxifloxacin) or Treatment D (a single oral dose of ACP-196 and moxifloxacin matching placebos) according to a randomization scheme. The washout period will be >= 5 days between each dose. The clinic attempted to contact participants using their standard procedures approximately 14 days after the last study drug (or placebo) administration to determine if any adverse events (AEs) had occurred since the last dose of study drug(s). An adverse event is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| ABCD | Experimental | Participant will receive a single oral dose of 4 study treatments with the sequences of ABCD. The washout period will be >= 5 days between each dose. |
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| BDAC | Experimental | Participant will receive a single oral dose of 4 study treatments with the sequences of BDAC. The washout period will be >= 5 days between each dose. |
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| CADB | Experimental | Participant will receive a single oral dose of 4 study treatments with the sequences of CADB. The washout period will be >= 5 days between each dose. |
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| DCBA | Experimental | Participant will receive a single oral dose of 4 study treatments with the sequences of DCBA. The washout period will be >= 5 days between each dose. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| ACP-196 | Drug | Participants will receive a single oral dose of 100 mg ACP-196 (1 x 100 mg capsule) on Day 1 (Treatment A) and 400 mg ACP-196 (4 x 100 mg capsules) on Day 1 (Treatment B) according to the randomization scheme. |
| Measure | Description | Time Frame |
|---|---|---|
| The QTcF Change From Baseline at Postdose Timepoints (dQTcF) | 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours postdose in each period |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Time-matched QTcF Interval Following Moxifloxicin Administration Compared With Matching Placebo | 1, 2, 3, and 4 hour post moxifloxicin dose in each period | |
| Change From Baseline in Heart Rate at Postdose Time Points | 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours postdose in each period |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Priti Patel, MD | Acerta Clinical Trials | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Celerion | Tempe | Arizona | 85283 | United States |
Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.
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AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool. Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
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| ID | Term |
|---|---|
| C000604908 | acalabrutinib |
| D000077266 | Moxifloxacin |
| ID | Term |
|---|---|
| D024841 | Fluoroquinolones |
| D042462 | 4-Quinolones |
| D015363 | Quinolones |
| D011804 | Quinolines |
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| Moxifloxacin 400 mg | Drug | Participants will receive a single oral dose of 400 mg moxifloxacin (1 x 400 mg tablet) on Day 1 (Treatment C) according to the randomization scheme. |
|
| Placebo | Drug | Participants will receive a single oral dose of ACP-196 matching placebo (4 x 100 mg matching placebo capsules) and moxifloxacin matching placebo (1 x 400 mg matching placebo tablet) on Day 1 (Treatment D) according to the randomization scheme. |
|
| Change From Baseline in PR Interval at Postdose Time Points | 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours postdose in each period |
| Change From Baseline in RR Interval at Postdose Time Points | 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours postdose in each period |
| Change From Baseline in QRS Interval at Postdose Time Points | 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours postdose in each period |
| Change From Baseline in QT Interval at Postdose Time Points | 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours postdose in each period |
| Number of Participants With Nonspecific T Waves Abnormality at Postdose Time Points | 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours postdose in each period |
| Number of Participants With Nonspecific U Waves Abnormality at Postdose Time Points | 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours postdose in each period |
| Area Under the Plasma Concentration-time Curve From Time 0 to Time of Last Measurable Concentration (AUC0-last) of ACP-196 | -0.5, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours postdose in each period |
| Area Under the Plasma Concentration-time Curve From Time 0 to Infinity (AUC0-inf) of ACP-196 | -0.5, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours postdose in each period |
| Percent of AUC0-inf Extrapolated (AUC%extrap) of ACP-196 | -0.5, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours postdose in each period |
| Maximum Measured Plasma Concentration (Cmax) of ACP-196 | -0.5, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours postdose in each period |
| Time of the Maximum Measured Plasma Concentration (Tmax) of ACP-196 | -0.5, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours postdose in each period |
| Apparent Terminal Elimination Rate Constant (λz) of ACP-196 | -0.5, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours postdose in each period |
| Apparent Terminal Elimination Half-life ( t½) of ACP-196 | -0.5, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours postdose in each period |
| Apparent Total Plasma Clearance (CL/F) of ACP-196 | -0.5, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours postdose in each period |
| Incidence of Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious AEs (TESAEs) | From Day 1 through 14 days after the last dose of study drug of the last period (approximately 1 month and 8 days) |
| Incidence of Abnormal Clinical Laboratory Parameters Reported as TEAEs | From Day 1 through 24 hours after the last dose of study drug of the last period (approximately 1 month and 8 days) |
| Incidence of Abnormal Vital Signs and Physical Examinations Reported as TEAEs | From Day 1 through 24 hours after the last dose of study drug of the last period (approximately 1 month and 8 days) |
| Incidence of Abnormal ECGs Reported as TEAEs | From Day 1 through 24 hours after the last dose of study drug of the last period (approximately 1 month and 8 days) |
| D006574 |
| Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |