Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Label indication BRILINTA is a P2Y 12 platelet inhibitor indicated to reduce the risk of cardiovascular (CV) death, myocardial infarction (MI), and stroke in patients with acute coronary syndrome (ACS) or a history of MI. For at least the first 12 months following ACS, it is superior to clopidogrel. BRILINTA also reduces the risk of stent thrombosis in patients who have been stented for treatment of ACS. FDA label
Also known as Ticagrelor, Brilique, Brilinta, Possia, SUB30898, B01AC24
AZD6140 · 21 trials · 21 indications
Participants with subsequent stroke or death
Participants with Cardiovascular (CV) death, myocardial infarction (MI) or stroke. If no event, censoring occurs at the earliest of PACD, last endpoint assessment date and non-CV death date.
Participants with stroke, MI or death. If no event, censoring occures at the minimum of (last date of event assessment, end of treatment date, day 97).
Participants with CV death, myocardial infarction (MI) or ischemic stroke. If no event, censoring occurs at the minimum of (primary analysis censoring date (PACD), last endpoint assessment date, non-CV death date)
Time to first occurrence of any major bleeding event (adjudicated by an independent Clinical Endpoint Committee (ICEC)). 1-year event rate (%) estimated via Kaplan-Meier method.
Time to first occurrence of any event from the composite of death from vascular causes, Myocardial Infarction (MI) and stroke (adjudicated by an ICEC). 1-year event rate (%) estimated via Kaplan-Meier method.
Participants with CV death, MI or Stroke. If no event, censoring occurs at the earliest of the efficacy cut-off date 14 Sep 2014, withdrawal of consent, non-CV death or at the last time point of complete clinical event assessment. Events were adjudicated by a blinded endpoint committee. The Kaplan-Meier estimate reports the percentage of patients who experienced CV Death, MI or stroke within 3 years from randomization
A Thrombolysis in Myocardial Infarction (TIMI) study group major bleeding is defined as any fatal bleeding (leading directly to death within 7 days), any intrcranial bleeding or any clinically overt signs of haemorrhage associated with a drop in Haemoglobin of \>= 5g/dL. Events were adjudicated by a clinical events committee. Censoring ocurrs at 7 days following last dose of study drug. The Kaplan-Meier estimate reports the percentage of patients who experienced a TIMI Major bleeding within 3 years from first dose of study drug
Participants with death from vascular causes, MI, or stroke. If no event, censoring occurs at the earliest of patient withdrawal consent or date of scheduled withdrawal from therapy. Intention To Treat (ITT) analysis of whole population. Events were adjudicated by an endpoint committee.
Participants with major (fatal/life-threatening or other) bleed by a study protocol scale based on need for treatment, number of transfusions, hemoglobin decrease, and other factors. Events were adjudicated by an endpoint committee.
To investigate the efficacy of 2 different doses of ticagrelor versus placebo in reducing the number of days with pain due to sickle cell disease.
Change from baseline in %IPA at 2 hours after stimulation with 20µM ADP (µM-micromolar, ADP-Adenosine diphosphate), measured in blood by an aggregometer among patients randomized to ticagrelor and 2 boluses of eptifibatide vs. ticagrelor and 2 boluses plus infusion of eptifibatide.
The primary outcome is the treatment difference in the mean change in cfPWV from baseline (0 hours) at 3 hours after the loading dose of each regimen, in ticagrelor and clopidogrel acute period populations.
Final extent IPA from pre-dose baseline was calculated using the following formula for Adenosine Diphosphate (ADP)-induced platelet aggregation: Percentage Inhibition = 100% x (PAs - PA) / (PAs) Platelet Aggregation (PA) was the mean response at the given post dose time point and PAs was the mean response at pre dose baseline. Percentage inhibition was restricted to the closed interval \[0,100\]; any data falling outside this range was truncated to the appropriate limit.
Final extent IPA from pre-dose baseline was calculated using the following formula for ADP-induced platelet aggregation: Percentage Inhibition = 100% x (PAs - PA) / (PAs) PA was the mean response at the given post dose time point and PAs was the mean response at pre dose baseline. Percentage inhibition was restricted to the closed interval \[0,100\]; any data falling outside this range was truncated to the appropriate limit.
Final extent IPA from pre-dose baseline was calculated using the following formula for ADP-induced platelet aggregation: Percentage Inhibition = 100% x (PAs - PA) / (PAs) PA was the mean response at the given post dose time point and PAs was the mean response at pre dose baseline. Percentage inhibition was restricted to the closed interval \[0,100\]; any data falling outside this range was truncated to the appropriate limit.
Final extent IPA from pre-dose baseline was calculated using the following formula for ADP-induced platelet aggregation: Percentage Inhibition = 100% x (PAs - PA) / (PAs) PA was the mean response at the given post dose time point and PAs was the mean response at pre dose baseline. Percentage inhibition was restricted to the closed interval \[0,100\]; any data falling outside this range was truncated to the appropriate limit.
Final extent IPA from pre-dose baseline was calculated using the following formula for ADP-induced platelet aggregation: Percentage Inhibition = 100% x (PAs - PA) / (PAs) PA was the mean response at the given post dose time point and PAs was the mean response at pre dose baseline. Percentage inhibition was restricted to the closed interval \[0,100\]; any data falling outside this range was truncated to the appropriate limit.
The primary definition of response to treatment is IPA \>10% post treatment. The response is reported as percentage of participants of each treatment. Please refer to the protocol section for details about the interventions administered. IPA(%)=(PAb-PAt)/PAb\*100. PA (platelet aggregation) is measured by LTA (Light Transmittance Aggregometry). PAb is the response at baseline (last measurement before study drug) and PAt is a response at post-treatment. IPA=0% means no PA inhibition and 100% means 100% PA inhibition.
The secondary definition of response to treatment is IPA \>50% post treatment. The response is reported as percentage of participants of each treatment. Please refer to the protocol section for details about the interventions administered. IPA(%)=(PAb-PAt)/PAb\*100. PA (platelet aggregation) is measured by LTA (Light Transmittance Aggregometry). PAb is the response at baseline (last measurement before study drug) and PAt is a response at post-treatment. IPA=0% means no PA inhibition and 100% means 100% PA inhibition.
IPA(%)=(PAb-PAt)/PAb\*100.The unit % is the percentage of difference for baseline versus post baseline value relative to baseline value of platelet aggregation. PA (platelet aggregation) is measured by LTA (Light Transmittance Aggregometry). PAb is the response at baseline (last measurement before study drug) and PAt is a response at post-treatment. IPA=0% means no PA inhibition and 100% means 100% PA inhibition.
IPA(%)=(PAb-PAt)/PAb\*100.The unit % is the percentage of difference for baseline versus post baseline value relative to baseline value of platelet aggregation. PA (platelet aggregation) is measured by LTA (Light Transmittance Aggregometry). PAb is the response at baseline (last measurement before study drug) and PAt is a response at post-treatment. IPA=0% means no PA inhibition and 100% means 100% PA inhibition. The unit for the slope of IPA curve is percent/hour.
This measure is obtained from observed plasma concentrations
This measure is obtained from the population PK analysis
This measure is obtained from the population PK analysis.
Number of Participants with prolonged bleeding (\>30 minutes) after removal of needles
| Arm | Type | Description |
|---|---|---|
| TICAGRELOR | EXPERIMENTAL | - |
| TICAGRELOR PLACEBO | PLACEBO_COMPARATOR | - |
| Ticagrelor 60 mg | EXPERIMENTAL | Initially ticagrelor 90 mg or corresponding placebo was the selected dose, but reduced to ticagrelor 60 mg or corresponding placebo in Clinical Study Protocol Amendment No 1. |
| Acetylsalicylic acid (ASA) | ACTIVE_COMPARATOR | - |
| Clopidogrel | ACTIVE_COMPARATOR | Clopidogrel 75 mg od (and Ticagrelor placebo bd) taken orally as tablets |
| 1 | EXPERIMENTAL | Ticagrelor (AZD6140) |
| 2 | ACTIVE_COMPARATOR | Clopidogrel |
| 3 | PLACEBO_COMPARATOR | Oral Treatment |
| Dose A | EXPERIMENTAL | - |
| Dose B | EXPERIMENTAL | - |
| Placebo | PLACEBO_COMPARATOR | - |
| 18F-F Positive - Ticagrelor | EXPERIMENTAL | Ticagrelor oral tablets, one (90mg) tablet, twice daily, 12 month duration |
| 18F-F Positive - Placebo | PLACEBO_COMPARATOR | Identical placebo, one tablet, twice daily, 12 month duration |
| 18F-F Negative - Ticagrelor | EXPERIMENTAL | Ticagrelor oral tablets, one (90mg) tablet, twice daily, 12 month duration |
| 18F-F Negative - Placebo | PLACEBO_COMPARATOR | Identical placebo, one tablet, twice daily, 12 month duration |
| Ticagrelor and Eptifibatide bolus | ACTIVE_COMPARATOR | Ticagrelor 180 mg i.v. Eptifibatide (2 boluses 180µg/Kg each 10 min apart) |
| Ticagrelor & Eptifibatide bolus+infusion | ACTIVE_COMPARATOR | Ticagrelor 180 mg i.v. Eptifibatide (2 boluses 180µg/Kg, 10 min apart, followed by 2µg/Kg/min infusion for 2 hours) |
| AZD6140 45 mg bd | EXPERIMENTAL | - |
| AZD6140 90 mg bd | EXPERIMENTAL | - |
| Clopidogrel 75 mg od | ACTIVE_COMPARATOR | - |
| Treatment arm | EXPERIMENTAL | Single dose of ticagrelor based on age |
| Sequence 1 | EXPERIMENTAL | hemodialysis patients: subjects will receive treatment A (ticagrelor oral 90 mg 1 day following the dialysis session but 2 days before the next dialysis session) in period 1 and treatment B (ticagrelor oral 90 mg just prior to dialysis session) in period 2. |
| Sequence 2 | EXPERIMENTAL | hemodialysis patients: subjects will receive treatment B (ticagrelor oral 90 mg just prior to dialysis session) in period 1 and treatment A (ticagrelor oral 90 mg 1 day following the dialysis session but 2 days before the next dialysis session) in period 2. |
| Treatment H | EXPERIMENTAL | Healthy subjects: ticagrelor oral 90 mg on 1 day of treatment |
| 4 | ACTIVE_COMPARATOR | Clopidogrel without Platelet transfusion |
| AZD6140 | EXPERIMENTAL | - |
| Name | Type | Description |
|---|---|---|
| Ticagrelor | DRUG | Ticagrelor arm: Day 1, loading dose of ticagrelor followed by daily maintenance dose until Day 30. |
| Placebo | DRUG | Placebo arm: Day 1, loading dose of placebo followed by placebo daily maintenance dose until Day 30. |
| Ticagrelor 60 mg | DRUG | Ticagrelor 60 mg bd taken orally as tablets |
| Ticagrelor placebo | DRUG | Ticagrelor placebo bd taken orally as tablets |
| Acetylsalicylic acid (ASA) | DRUG | ASA, 300 mg (three tablets of 100 mg) on Day 1, followed by 100 mg once daily. |
| Clopidogrel | DRUG | Clopidogrel 75 mg od (and Ticagrelor placebo bd) taken orally as tablets |
| Acetylsalicylic acid ASA | DRUG | Low Dose ASA |
| Ticagrelor 90 mg | DRUG | Oral dose twice a day |
| Eptifibatide | DRUG | i.v. infusion |
| Aspirin | DRUG | Tablets, Oral, 75 mg to 100 mg once daily. Aspirin obtained locally by the investigator, according to local practice. The dose remained constant throughout the study |
| Ticagrelor Tablets | DRUG | Oral, 90 mg; 180 mg loading dose followed by 90 mg twice daily (BD) |
| Clopidogrel (over encapsulated) capsule | DRUG | Oral 75 mg; 600 mg loading dose followed by 75 mg once daily (ODD) |
| Aspirin Tablets | DRUG | Oral, 75 mg to 100 mg once daily. Aspirin obtained locally by the investigator, according to local practice. The dose remained constant throughout the study. |
| ASA | DRUG | 81mg once daily from day -2 up to platelet transfusion |
| AZD6140 | DRUG | P2Y12 receptor antagonist |
| Placebo to match AZD6140 | DRUG | Oral tablets taken bid for 5 days |
Inclusion Criteria: 1. Provision of signed informed consent prior to any study-specific procedure 2. ≥40 years of age 3. Acute onset of cerebral ischaemia due to 1. AIS with NIHSS ≤5. AIS is defined as acute onset of neurological deficit attributed to focal brain ischaemia, and either of the fo...
AZD6140 is an investigational small molecule developed by AstraZeneca PLC (ticker AZN). It has been studied in Phase 1 clinical trials for blood flow speed, gout, and renal impairment, and it falls within the cardiovascular therapeutic area. It is not described as approved and remains in clinical development.
AZD6140 is made by AstraZeneca PLC, which trades under the ticker AZN. AstraZeneca is the developer of the compound and has sponsored the Phase 1 studies conducted with it.
AZD6140 is in Phase 1 clinical development. All of its listed trials are Phase 1 studies, and the program has one completed trial with no active trials currently listed. It is an investigational agent and is not described as approved.
AZD6140 has been evaluated in Phase 1 trials including NCT01226602, which assessed its effect on coronary blood flow in healthy male subjects in Sweden, and NCT00733265, which investigated its effects in patients with renal impairment and healthy volunteers in the United States. All listed trials are completed.
AZD6140 has been studied in Phase 1 trials for gout and renal impairment. One completed study, NCT00738842, examined uric acid in healthy male volunteers with gout and coronary artery disease, and NCT00733265 investigated its effects in patients with renal impairment and healthy volunteers.