Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Cangrelor · 6 trials · 4 indications
A reference point for prasugrel or clopidogrel was chosen for comparison and designated at 6 or 5.5 hrs after the administration of prasugrel or clopidogrel as the reference for the effect of the oral drug. Platelet function was assessed using light transmittance aggregometry (LTA). LTA measures the aggregation or cross linking of platelets by fibrinogen and requires the activation of platelets plus the binding of fibrinogen. The extent of aggregation was expressed as % aggregation in response to 20 micromolar (μM) adenosine diphosphate (ADP) at 300 seconds (sec) (final/terminal aggregation response).
A reference point for cangrelor was chosen for comparison and designated as the administration time of prasugrel 60 mg or clopidogrel 600 mg (2.5, 2, 1.5, or 1 hrs). Platelet function was assessed using LTA. LTA measures the aggregation or cross linking of platelets by fibrinogen and requires the activation of platelets plus the binding of fibrinogen. The extent of aggregation was examined using LTA and expressed as % aggregation in response to 20 μM ADP at 300 sec (final/terminal aggregation response).
A reference point for the effect of prasugrel alone was chosen for comparison and designated the final draw on study Day 1 (3.5 or 4.0 hours after cangrelor had been discontinued) as the reference for the effect of prasugrel. The extent of aggregation in the presence or absence of the study drugs was examined for each of the endpoints using light transmittance aggregometry (LTA) and expressed as % aggregation in response to 20 micromolar (μM) adenosine diphosphate (ADP) at 300 seconds (final/terminal aggregation response).
A reference point for the inhibitory effect of cangrelor alone was chosen for comparison and designated the first draw during the cangrelor infusion (1.0 or 1.5 hours) or within 5 minutes post cangrelor infusion on Day 1. The extent of aggregation was observed during the cangrelor infusion on Day 8, either 24 or 48 hours after discontinuation of prasugrel using light transmittance aggregometry (LTA) and expressed as % aggregation in response to 20 μM adenosine diphosphate (ADP) at 300 seconds (final/terminal aggregation response).
A reference point was chosen for comparison and designated the first draw during the cangrelor infusion (0.5 hours or 1.25 hours) as the reference for the effect of cangrelor and designated the final draw on study Day 1 (5.25 hours, or 3.25 hours after cangrelor had been discontinued) as the reference for the effect of ticagrelor. Residual platelet reactivity (the extent of aggregation in the presence or absence of the study drugs) was examined for each of the endpoints using light transmittance aggregometry. Residual platelet reactivity (PR) was measured in response to 20 µmol adenosine diphosphate (ADP) at 300 seconds (final/terminal aggregation response).
A reference point was chosen for comparison and designated the first draw during the cangrelor infusion (0.5 hours or 1.25 hours) as the reference for the effect of cangrelor. Residual platelet reactivity (the extent of aggregation in the presence or absence of the study drugs) was examined for each of the endpoints using light transmittance aggregometry (LTA). Residual platelet reactivity (PR) was measured in response to 20 µmol ADP at 300 seconds (final/terminal aggregation response).
Blood samples were taken for platelet function studies to conduct pharmacodynamic assessments including LTA. A reference point was chosen for comparison and designated the first draw during the cangrelor infusion (0.5 hours or 1.25 hours) as the reference for the effect of cangrelor and designated the final draw on study Day 1 (5.25 hours, or 3.25 hours after cangrelor had been discontinued) as the reference for the effect of ticagrelor. Residual platelet reactivity (PR) (the extent of aggregation in the presence or absence of the study drugs) was examined for each of the endpoints using light transmittance aggregometry. Residual platelet reactivity was measured in response to 20 µmol ADP at 300 seconds (final/terminal aggregation response).
Endpoint was selected as an approximation of the antiplatelet effect expected to be maintained if oral P2Y12 inhibitors had not been discontinued (60% inhibition of platelets).
This endpoint was selected as it is considered by consensus of the Working Group on Platelet Reactivity to be the threshold for the level of platelet inhibition required to maintain a low risk of coronary thrombosis and cardiac ischemic events. Patients had multiple samples and all "on-infusion" samples had to be \<240 PRU to meet the endpoint.
| Arm | Type | Description |
|---|---|---|
| Prasugrel 30 Min After Cangrelor | EXPERIMENTAL | Prasugrel 60 milligram (mg) administered orally 30 min after the discontinuation of cangrelor infusion on Day 1 (2.5 hours \[hrs\] after initiation of cangrelor infusion). |
| Clopidogrel Within 5 Min After Cangrelor | EXPERIMENTAL | Clopidogrel 600 mg administered orally within 5 min after the discontinuation of the cangrelor infusion on Day 1 (2 hrs after initiation of cangrelor infusion). |
| Clopidogrel 1.5 Hrs During Cangrelor | EXPERIMENTAL | Clopidogrel 600 mg administered orally 1.5 hrs after the initiation of cangrelor infusion on Day 1. |
| Clopidogrel 1 Hr During Cangrelor | EXPERIMENTAL | Clopidogrel 600 mg administered orally 1 hr after the initiation of cangrelor infusion on Day 1. |
| Day 1 - Cangrelor + Prasugrel (60mg) post infusion | EXPERIMENTAL | Cangrelor IV + Oral prasugrel (60mg) administered within 5 minutes after cangrelor IV discontinuation |
| Day 8 - Prasugrel (10mg) Dosing (5 doses) | EXPERIMENTAL | Prasugrel discontinued 48h (n=6) prior to initiation of cangrelor infusion (2h) |
| Day 1 - Cangrelor + Prasugrel (60mg) at 1.5h | EXPERIMENTAL | Cangrelor IV + oral prasugrel (60mg) administered at 1.5h after the cangrelor infusion start time. |
| Day 1 - Cangrelor + Prasugrel (60mg) a 1.0h | EXPERIMENTAL | Cangrelor IV + oral prasugrel (60mg) administered at 1.0h after the cangrelor infusion start time. |
| Day 8 - Prasugrel (10mg) Dosing (6 doses) | EXPERIMENTAL | Prasugrel discontinued 24h prior to initiation of cangrelor infusion (2h) |
| Cangrelor IV + Ticagrelor 180mg at 0.5 hr | EXPERIMENTAL | On Day 1: Open-label cangrelor IV bolus (30 µg/kg), followed by an infusion of 4 µg/kg/min for two hours. Ticagrelor (180 mg) was administered at 0.5 h after the initiation of cangrelor infusion. |
| Cangrelor IV + Ticagrelor 90mg (7 doses) | EXPERIMENTAL | On Day 1: Following completion of cangrelor and ticagrelor dosing, patients were discharged and instructed to take 90 mg ticagrelor every 12 hours for 7 doses (12, 24, 36, 48, 60, 72, and 84 h). On Day 5: 12 h post last ticagrelor dose (90 mg), patients received another open-label cangrelor IV bolus (30 µg/kg), followed by an infusion of 4 µg/kg/min for two hours. |
| Cangrelor IV + Ticagrelor 180mg at 1.5 hr | EXPERIMENTAL | On Day 1: Open-label cangrelor IV bolus (30 µg/kg), followed by an infusion of 4 µg/kg/min for two hours. Ticagrelor (180 mg) was administered at 1.5 h after the initiation of cangrelor infusion. |
| Cangrelor IV + Ticagrelor 90mg (6 doses) | EXPERIMENTAL | On Day 1: Following completion of cangrelor and ticagrelor dosing, patients were discharged and instructed to take 90 mg ticagrelor every 12 hours for 6 doses (12, 24, 36, 48, 60, and 72 h). On Day 5: 24 h post last ticagrelor dose (90 mg), patients received another open-label cangrelor IV bolus (30 µg/kg), followed by an infusion of 4 µg/kg/min for two hours. |
| Cangrelor | EXPERIMENTAL | Cangrelor was administered as a continuous IV infusion of 0.75µg/kg/min for a minimum of 48 hours and a maximum of 7 days. |
| Placebo | PLACEBO_COMPARATOR | A placebo infusion was administered as a continuous IV infusion of 0.75µg/kg/min for a minimum of 48 hours and a maximum of 7 days, to maintain the blind. |
| Lead in Phase | EXPERIMENTAL | Supratherapeutic dose of cangrelor |
| A | EXPERIMENTAL | therapeutic dose cangrelor treatment |
| B | EXPERIMENTAL | supratherapeutic dose cangrelor treatment |
| C | ACTIVE_COMPARATOR | active comparator treatment |
| D | PLACEBO_COMPARATOR | placebo treatment |
| Name | Type | Description |
|---|---|---|
| Cangrelor | DRUG | Cangrelor intravenously (IV) administered as a 30 microgram (µg)/kilogram (kg) bolus, followed by 4 µg/kg/min infusion for 2 hrs on Day 1. |
| Clopidogrel | DRUG | Clopidogrel 600 mg single oral dose |
| Prasugrel | DRUG | Prasugrel 60 mg single oral dose |
| Ticagrelor | DRUG | Ticagrelor 180mg dose: administered 0.5 h or 1.5h after the initiation of cangrelor infusion Ticagrelor 90mg: 6 or 7 doses (depending on study arm) taken every 12 hours post cangrelor infusion. |
| Placebo | OTHER | Placebo IV infusion administered in the same fashion as the active study drug in order to maintain the blind in the study. |
| moxifloxacin | DRUG | 400 mg orally. Placebo IV bolus and infusion. |
Inclusion Criteria: 1. Greater than or equal to 18 and less than 75 years of age, of either sex, and of any race. 2. Stable CAD defined by the following criteria: 1. Previous myocardial infarction defined by admission to the hospital with elevation of markers of injury or the presence of pathol...
Cangrelor is an investigational small molecule being developed for cardiovascular conditions, specifically Acute Coronary Syndrome (ACS) and Coronary Artery Disease (CAD). It is being studied in Phase 2 clinical trials to evaluate its effects in these patient populations.
Cangrelor is being developed by Novartis AG, a multinational pharmaceutical company. Novartis is listed on the stock exchange under the ticker symbol NVS.
Cangrelor is currently in Phase 2 clinical development. It is an investigational drug and has not been approved by regulatory authorities. All completed trials for Cangrelor are Phase 2 studies.
Cangrelor has been studied in several completed Phase 2 clinical trials. These include NCT00767507, which enrolled 221 participants with Acute Coronary Syndrome, and NCT01766466, NCT01852019, and NCT01979445, which studied transitions to other antiplatelet agents in patients with Coronary Artery Disease.
Cangrelor is a distinct drug and is not the same as other antiplatelet agents. Clinical trials have studied transitions from Cangrelor to ticagrelor, prasugrel, and clopidogrel, indicating it is a separate medication with its own mechanism of action.