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The purpose of this study is to assess the pharmacodynamic effect of ticagrelor in Hispanic patients with stable coronary artery disease.
A Randomized, Open-Label, Multiple Dose, Crossover, Multiple Center Study of the Antiplatelet Effects of Ticagrelor versus Clopidogrel in Hispanic Patients with Stable Coronary Artery Disease
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Ticagrelor | Experimental |
| |
| Clopidogrel | Active Comparator |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Ticagrelor | Drug | Min - 90mg/Max - 180mg tablets (loading dose) |
| |
| Measure | Description | Time Frame |
|---|---|---|
| Inhibition of the P2Y12 Receptor as Measured by P2Y12 Reactions Units (PRU) From VerifyNow™ (a Platelet Function Test Developed by Accumetrics) at 2 Hours After Loading Dose | Participants with low (<150) baseline PRU values (indicating an incomplete washout from anti-platelet therapy) were excluded during the period corresponding to the low baseline value | At 2 hours after the loading dose |
| Measure | Description | Time Frame |
|---|---|---|
| Inhibition of the P2Y12 Receptor as Measured by PRU From VerifyNow™ at 0.5 and 8 Hours After Loading Dose | Participants with low (<150) baseline PRU values (indicating an incomplete washout from anti-platelet therapy) were excluded during the period corresponding to the low baseline value | At 0.5 and 8 hours after the loading dose |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Glenn Carlson, MD | AstraZeneca PharmaceuticalsRoom C3B-718PO Box 15437Wilmington, DE 19850-5437 USA | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Research Site | Los Angeles | California | United States | |||
| Research Site |
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| Label | URL |
|---|---|
| D5130L00012\_Clinical\_Study\_Protocol\_Redacted | View source |
| CSR\_Synopsis | View source |
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53 patients screened; 40 patients randomized; 38 patients completed the study (7, 8, or 9 days of both treatment sequences), and 39 completed follow-up.
Patients recruited from 6 centers in the United States from April 2012 until May 2013.
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| ID | Title | Description |
|---|---|---|
| FG000 | Ticagrelor (Period 1) Then Clopidogrel (Period 2) Sequence | Ticagrelor 180 milligrams (mg) loading dose followed by 90 mg twice daily (bd) for 7,8 or 9 days (Period 1), and then clopidogrel 600 mg loading dose followed by 75 mg once daily (od) for 7, 8 or 9 days (Period 2). |
| FG001 | Clopidogrel (Period 1) Then Ticagrelor (Period 2) Sequence | Clopidogrel 600 mg loading dose followed by 75 mg od for 7, 8 or 9 days (Period 1), then ticagrelor 180 mg loading dose followed by 90 mg bd for 7,8 or 9 days (Period 2) |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Treatment Period 1 |
|
| ||||||||||||||||||
| Washout Period - 10-14 Days |
| |||||||||||||||||||
| Treatment Period 2 |
|
Randomized Analysis Set for demography (N=40) - included all patients who signed informed consent and were randomized into the study. Pharmacodynamic (PD) Analysis Set for outcomes (N=38) - included all patients for whom PD data was available with no major protocol deviations thought to significantly affect the PD of ticagrelor or clopidogrel
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| ID | Title | Description |
|---|---|---|
| BG000 | Ticagrelor (Period 1) Then Clopidogrel (Period 2) Sequence | Ticagrelor 180 milligrams (mg) loading dose followed by 90 mg twice daily (bd) for 7,8 or 9 days (Period 1), and then clopidogrel 600 mg loading dose followed by 75 mg once daily (od) for 7, 8 or 9 days (Period 2). |
| BG001 | Clopidogrel (Period 1) Then Ticagrelor (Period 2) Sequence |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Customized | Number |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Inhibition of the P2Y12 Receptor as Measured by P2Y12 Reactions Units (PRU) From VerifyNow™ (a Platelet Function Test Developed by Accumetrics) at 2 Hours After Loading Dose | Participants with low (<150) baseline PRU values (indicating an incomplete washout from anti-platelet therapy) were excluded during the period corresponding to the low baseline value | Pharmacodynamic (PD) Analysis Set | Posted | Least Squares Mean | 95% Confidence Interval | PRU | At 2 hours after the loading dose |
|
Adverse events were collected from the time of signature of the informed consent throughout the treatment period including the follow up visit (approximately 11 weeks for each participant).
Adverse events were solicited at each scheduled visit and could be reported by the participant at any time during the study. When summarizing Treatment Period 1 and Treatment Period 2 totals, each participant was counted only once for an individual adverse event, regardless of whether it occurred on ticagrelor, clopidogrel or both.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Ticagrelor Arm | Ticagrelor 180 mg loading dose followed by 90 mg bd for 7,8 or 9 days. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Diarrhea | Gastrointestinal disorders | Systematic Assessment |
Total N for the secondary outcome analysis after multiple doses and for PK measures was not the same for 2 hours, 8 hours and end of dosing. Only the first time point total N can be reported via the form. Row titles indicate N's where they differ.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Tomas LG Andersson, MD, PhD | AstraZeneca | 1-800-236-9933 | ClinicalTrialTransparency@astrazeneca.com |
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| ID | Term |
|---|---|
| D000077486 | Ticagrelor |
| D000077144 | Clopidogrel |
| ID | Term |
|---|---|
| D000241 | Adenosine |
| D011684 | Purine Nucleosides |
| D011687 | Purines |
| D006574 | Heterocyclic Compounds, 2-Ring |
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| Clopidogrel |
| Drug |
75mg (once daily)/Max - 600mg tablets (loading dose) |
|
| Inhibition of the P2Y12 Receptor as Measured by PRU From VerifyNow™ at 2 and 8 Hours on Day 7 After Multiple Doses and at End of Dosing Interval on Day 8 |
The end of dosing interval was approximately 12 hours after the last evening dose of ticagrelor and approximately 24 hours after the last morning dose of clopidogrel. Participants with low (<150) baseline PRU values (indicating an incomplete washout from anti-platelet therapy) were excluded during the period corresponding to the low baseline value |
| At 2 hours and 8 hours on Day 7 after multiple doses, and at the end of dosing interval on Day 8 |
| Ticagrelor Plasma Concentrations After the Loading and Maintenance Doses | The standard deviation (SD) is a statistic using the log-transformed data and is not the geometric SD. | Predose, 0.5, 2, 8 hours from loading dose; 0, 2, 8 and 12 hours from last dose |
| AR-C124910XX (an Active Metabolite of Ticagrelor) Plasma Concentrations After the Loading and Maintenance Doses | The SD is a statistic using the log-transformed data and is not the geometric SD. | Predose, 0.5, 2, 8 hours from loading dose; 0, 2, 8 and 12 hours from last dose |
| Hollywood |
| Florida |
| United States |
| Research Site | Jacksonville | Florida | United States |
| Research Site | Miami | Florida | United States |
| Research Site | Linden | New Jersey | United States |
| NOT COMPLETED |
|
| NOT COMPLETED |
|
|
Clopidogrel 600 mg loading dose followed by 75 mg od for 7, 8 or 9 days (Period 1), then ticagrelor 180 mg loading dose followed by 90 mg bd for 7,8 or 9 days (Period 2) |
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Number | Participants |
|
| Race/Ethnicity, Customized | Number | Participants |
|
| Region of Enrollment | Number | Participants |
|
| Region of Enrollment | Number | Participants |
|
|
|
|
| Secondary | Inhibition of the P2Y12 Receptor as Measured by PRU From VerifyNow™ at 0.5 and 8 Hours After Loading Dose | Participants with low (<150) baseline PRU values (indicating an incomplete washout from anti-platelet therapy) were excluded during the period corresponding to the low baseline value | PD Analysis Set | Posted | Least Squares Mean | 95% Confidence Interval | PRU | At 0.5 and 8 hours after the loading dose |
|
|
|
|
| Secondary | Inhibition of the P2Y12 Receptor as Measured by PRU From VerifyNow™ at 2 and 8 Hours on Day 7 After Multiple Doses and at End of Dosing Interval on Day 8 | The end of dosing interval was approximately 12 hours after the last evening dose of ticagrelor and approximately 24 hours after the last morning dose of clopidogrel. Participants with low (<150) baseline PRU values (indicating an incomplete washout from anti-platelet therapy) were excluded during the period corresponding to the low baseline value | PD Analysis Set | Posted | Least Squares Mean | 95% Confidence Interval | PRU | At 2 hours and 8 hours on Day 7 after multiple doses, and at the end of dosing interval on Day 8 |
|
|
|
|
| Secondary | Ticagrelor Plasma Concentrations After the Loading and Maintenance Doses | The standard deviation (SD) is a statistic using the log-transformed data and is not the geometric SD. | Pharmacokinetic (PK) Analysis Set, defined as all participants for whom at least one valid PK reading was available | Posted | Geometric Mean | Standard Deviation | ng/mL | Predose, 0.5, 2, 8 hours from loading dose; 0, 2, 8 and 12 hours from last dose |
|
|
|
| Secondary | AR-C124910XX (an Active Metabolite of Ticagrelor) Plasma Concentrations After the Loading and Maintenance Doses | The SD is a statistic using the log-transformed data and is not the geometric SD. | PK Analysis Set | Posted | Geometric Mean | Standard Deviation | ng/mL | Predose, 0.5, 2, 8 hours from loading dose; 0, 2, 8 and 12 hours from last dose |
|
|
|
| 0 |
| 40 |
| 5 |
| 40 |
| EG001 | Clopidogrel Arm | Clopidogrel 600 mg loading dose followed by 75 mg od for 7, 8 or 9 days. | 0 | 39 | 6 | 39 |
| Abdominal pain upper | Gastrointestinal disorders | Systematic Assessment |
|
| Dyspnea | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Oropharyngeal discomfort | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Malaise | General disorders | Systematic Assessment |
|
| Heart rate irregular | Investigations | Systematic Assessment |
|
| Heart rate increased | Investigations | Systematic Assessment |
|
| Headache | Nervous system disorders | Systematic Assessment |
|
| Dizziness | Nervous system disorders | Systematic Assessment |
|
| Dysgeusia | Nervous system disorders | Systematic Assessment |
|
| Burning Sensation | Nervous system disorders | Systematic Assessment |
|
| Fall | Injury, poisoning and procedural complications | Systematic Assessment |
|
| Rib fracture | Injury, poisoning and procedural complications | Systematic Assessment |
|
| Nasopharyngitis | Infections and infestations | Systematic Assessment |
|
| Musculoskeletal chest pain | Musculoskeletal and connective tissue disorders | Systematic Assessment |
|
An Investigator agrees to provide a copy of the publication to AstraZeneca (AZ) for review at least 60 days in advance of the submission for publication. The Investigators in the Multi-Center (MC) study agree to postpone MC publications until the earlier of the first AZ-authorized publication or up to 18 months from study completion at all sites.
| D000072471 |
| Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
| D009705 | Nucleosides |
| D009706 | Nucleic Acids, Nucleotides, and Nucleosides |
| D012263 | Ribonucleosides |
| D013988 | Ticlopidine |
| D058924 | Thienopyridines |
| D013876 | Thiophenes |
| D013457 | Sulfur Compounds |
| D009930 | Organic Chemicals |
| D011725 | Pyridines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| Analysis at 8 hours after the loading dose | Mixed Models Analysis | Model contained treatment group, period, and sequence as fixed effects, and a random effect for participant within sequence | <.001 | Mean Difference (Final Values) | -168.9 | Standard Error of the Mean | 17.28 | 2-Sided | 95 | -204.0 | -133.7 | Ticagrelor minus Clopidogrel | No | Superiority or Other |
| End of Dosing Interval on Day 8 - N's per 8 hours |
|
| Analysis at 8 hours on Day 7 after multiple doses | Mixed Models Analysis | Model contained treatment group, period, and sequence as fixed effects, and a random effect for participant within sequence | <.001 | Mean Difference (Final Values) | -140.2 | Standard Error of the Mean | 13.84 | 2-Sided | 95 | -168.4 | -111.9 | Ticagrelor minus clopidogrel. | No | Superiority or Other |
| Analysis at end of dosing interval on Day 8 | Mixed Models Analysis | Model contained treatment group, period, and sequence as fixed effects, and a random effect for participant within sequence | <.001 | Mean Difference (Final Values) | -130.6 | Standard Error of the Mean | 13.41 | 2-Sided | 95 | -158.0 | -103.2 | Ticagrelor minus clopidogrel. | No | Superiority or Other |
| 2 hours after the loading dose - Period 2 N=18 |
|
| 8 hours after the loading dose |
|
| 0 hours after multiple doses |
|
| 2 hours after multiple doses |
|
| 8 hours after multiple doses |
|
| End of dosing interval on Day 8 - Period 1 N=17 |
|
| 2 hours after the loading dose - Period 2 N=18 |
|
| 8 hours after the loading dose |
|
| 0 hours after multiple doses |
|
| 2 hours after multiple doses |
|
| 8 hours after multiple doses |
|
| End of dosing interval on Day 8 - Period 1 N=17 |
|