Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as Clopidogrel (SR25990), clopidogrel (SR25990C), clopidogrel (SR25990)
Clopidogrel · 20 trials · 18 indications
All bleeding events experienced during the study period were collected as for any Adverse Event. The 'on-treatment' period was defined as the period from inclusion in the extension study up to 28 days after treatment discontinuation, and participants who experienced bleeding events during that period were counted.
For all reported bleeding events, the type and the etiology of the bleeding event were collected. Participants who experienced bleeding events during the 'on-treatment period' were counted by bleeding type and etiology.
Safety events of interest were: * Clinically significant bleeding, * Leukopenia, neutropenia or thrombocytopenia occurring as adverse drug reaction, * Elevated liver function values occurring as adverse drug reaction, * Permanent investigational product discontinuation due to skin disorders, gastrointestinal disorders, bleeding, hepatic disorders, or significant decreases in such tests as leukocytes, neutrophils or platelets occurring as adverse drug reaction.
The primary endpoint was the first occurence of any of the following events: Death (including heart transplant); Shunt thrombosis requiring intervention; Hospitalization for bi-directional Glenn procedure or any cardiac related intervention prior to 120 days of age following an event or a shunt narrowing considered to be of thrombotic nature by the blinded adjudication committee. Only the first event was counted.
The primary endpoint is the first occurrence of any of the following events: * Cardiovascular death (any death with a clear cardiovascular or unknown cause), * Myocardial Infarction (diagnosis of new Myocardial Infarction (MI) - nonfatal or fatal) * Stroke (presence of a new focal neurologic deficit thought to be vascular in origin, with signs or symptoms lasting more than 24 hours - nonfatal or fatal) reported between the randomization and Day 30 (inclusive), and validated by the blinded Event Adjudication Committee (EAC).
The primary event is the first occurence of any adjudicated component of the following cluster over the duration of follow-up : * stroke (nonfatal or fatal) * myocardial infarction (nonfatal or fatal) * non-CNS systemic embolism * vascular death The primary efficacy analysis is performed on the time from randomization to this primary event. Numbers of patients with the composite event over the duration of the follow-up are presented by arm group.
| Arm | Type | Description |
|---|---|---|
| Clopidogrel | EXPERIMENTAL | 75 mg clopidogrel once daily from Day 1 to Week 12 |
| Ticlopidine | ACTIVE_COMPARATOR | 200 mg ticlopidine once daily from Day 1 to Week 12 |
| Placebo | PLACEBO_COMPARATOR | 0.2 mL/kg/day matching placebo solution once daily. |
| Clopidogrel 0.2 mg/kg/day | EXPERIMENTAL | 0.2 mL/kg/day Clopidogrel reconstituted solution at 1mg/mL once daily. |
| Clopidogrel high dose treatment regimen + ASA high dose | EXPERIMENTAL | - |
| Clopidogrel high dose treatment regimen + ASA low dose | EXPERIMENTAL | - |
| Clopidogrel standard treatment regimen + ASA high dose | ACTIVE_COMPARATOR | - |
| Clopidogrel standard treatment regimen + ASA low dose | ACTIVE_COMPARATOR | - |
| 1 | EXPERIMENTAL | 300-mg loading dose of clopidogrel given ≥ 6 and ≤ 24 hours before PCI |
| 2 | EXPERIMENTAL | 600-mg loading dose of clopidogrel given ≥ 6 hours and ≤ 24 before PCI. |
| 3 | EXPERIMENTAL | 600-mg loading dose of clopidogrel given immediately (≤ 45 minutes) before PCI. |
| Clopidogrel + ASA | EXPERIMENTAL | Clopidogrel 75 mg once daily (od) plus acetylsalicyclic acid (ASA) 75 to 100 mg od recommended (dose at the investigators' discretion) |
| Placebo + ASA | PLACEBO_COMPARATOR | Matching placebo of clopidogrel 75 mg od plus acetylsalicyclic acid (ASA) 75 to 100 mg od recommended (dose at the investigators' discretion) |
| Group clopidogrel - clopidogrel + pantoprazole | EXPERIMENTAL | Period 1: * Day 1: clopidogrel 300 mg loading dose * Day 2 to Day 5: clopidogrel 75 mg, once daily Period 2: * Day -7 to Day -1: pantoprazole 80 mg, once daily * Day 1: clopidogrel 300 mg loading dose + pantoprazole 80 mg concomitantly * Day 2 to Day 5: clopidogrel 75 mg + pantoprazole 80 mg concomitantly, once daily Each intake is under fasted conditions. |
| Group placebo - placebo + pantoprazole | PLACEBO_COMPARATOR | Period 1: * Day 1: placebo loading dose * Day 2 to Day 5: placebo, once daily Period 2: * Day -7 to Day -1: pantoprazole 80 mg, once daily * Day 1: placebo loading dose + pantoprazole 80 mg concomitantly * Day 2 to Day 5: placebo + pantoprazole 80 mg concomitantly, once daily Each intake is under fasted conditions. |
| Group clopidogrel + pantoprazole - clopidogrel | EXPERIMENTAL | Period 1: * Day -7 to Day -1: pantoprazole 80 mg, once daily * Day 1: clopidogrel 300 mg loading dose + pantoprazole 80 mg concomitantly * Day 2 to Day 5: clopidogrel 75 mg + pantoprazole 80 mg concomitantly, once daily Period 2: * Day 1: clopidogrel 300 mg loading dose * Day 2 to Day 5: clopidogrel 75 mg, once daily Each intake is under fasted conditions. |
| Group placebo + pantoprazole placebo | PLACEBO_COMPARATOR | Period 1: * Day -7 to Day -1: pantoprazole 80 mg, once daily * Day 1: placebo loading dose + pantoprazole 80 mg concomitantly * Day 2 to Day 5: placebo + pantoprazole 80 mg concomitantly, once daily Period 2: * Day 1: placebo loading dose * Day 2 to Day 5: placebo, once daily Each intake is under fasted conditions. |
| Group clopidogrel - clopidogrel + omeprazole | EXPERIMENTAL | Period 1: * Day 1: clopidogrel 600 mg loading dose * Day 2 to Day 5: clopidogrel 150 mg, once daily Period 2: * Day -5 to Day -1: omeprazole 80 mg, once daily * Day 1: clopidogrel 600 mg loading dose + omeprazole 80 mg concomitantly * Day 2 to Day 5: clopidogrel 150 mg + omeprazole 80 mg concomitantly, once daily Each intake is under fasted conditions |
| Group placebo - placebo + omeprazole | PLACEBO_COMPARATOR | Period 1: * Day 1: placebo loading dose * Day 2 to Day 5: placebo, once daily Period 2: * Day -5 to Day -1: omeprazole 80 mg, once daily * Day 1: placebo loading dose + omeprazole 80 mg concomitantly * Day 2 to Day 5: placebo + omeprazole 80 mg concomitantly, once daily Each intake is under fasted conditions |
| Group clopidogrel + omeprazole - clopidogrel | EXPERIMENTAL | Period 1: * Day -5 to Day -1: omeprazole 80 mg, once daily * Day 1: clopidogrel 600 mg loading dose + omeprazole 80 mg concomitantly * Day 2 to Day 5: clopidogrel 150 mg + omeprazole 80 mg concomitantly, once daily Period 2: * Day 1: clopidogrel 600 mg loading dose * Day 2 to Day 5: clopidogrel 150 mg, once daily Each intake is under fasted conditions |
| Group placebo + omeprazole placebo | PLACEBO_COMPARATOR | Period 1: * Day -5 to Day -1: omeprazole 80 mg, once daily * Day 1: placebo loading dose + omeprazole 80 mg concomitantly * Day 2 to Day 5: placebo + omeprazole 80 mg concomitantly, once daily Period 2: * Day 1: placebo loading dose * Day 2 to Day 5: placebo, once daily Each intake is under fasted conditions |
| Group clopidogrel fed - fasting | EXPERIMENTAL | Period 1: * Day 1: clopidogrel 300 mg loading dose with high fat breakfast * Day 2 to Day 5: clopidogrel 75 mg/day with standard breakfast, once daily Period 2: * Day 1: clopidogrel 300 mg loading dose under fasted conditions * Day 2 to Day 5: clopidogrel 75 mg/day under fasted conditions, once daily |
| Group placebo fed - fasting | PLACEBO_COMPARATOR | Period 1: * Day 1: placebo loading dose with high fat breakfast * Day 2 to Day 5: placebo with standard breakfast, once daily Period 2: * Day 1: placebo loading dose under fasted conditions * Day 2 to Day 5: placebo under fasted conditions, once daily |
| Group clopidogrel fasting - fed | EXPERIMENTAL | Period 1: * Day 1: clopidogrel 300 mg loading dose under fasted conditions * Day 2 to Day 5: clopidogrel 75 mg/day under fasted conditions, once daily Period 2: * Day 1: clopidogrel 300 mg loading dose with high fat breakfast * Day 2 to Day 5: clopidogrel 75 mg/day with standard breakfast, once daily |
| group placebo fasting -fed | PLACEBO_COMPARATOR | Period 1: * Day 1: placebo loading dose under fasted conditions * Day 2 to Day 5: placebo in fasted conditions, once daily Period 2: * Day 1: placebo loading dose with high fat breakfast * Day 2 to Day 5: placebo with standard breakfast, once daily |
| Sequence clopidogrel 300/75 mg - 600/150 mg | EXPERIMENTAL | Period 1: * Day 1: clopidogrel, 300 mg loading dose + placebo * Day 2 to Day 5: clopidogrel, 75 mg + placebo, once daily Period 2: * Day 1: clopidogrel, 600 mg loading dose * Day 2 to Day 5: clopidogrel, 150 mg, once daily Each intake is at around 8:00 AM fasted for at least 10 hours |
| Sequence clopidogrel 600/150 mg - 300/75 mg | EXPERIMENTAL | Period 1: * Day 1: clopidogrel, 600 mg loading dose * Day 2 to Day 5: clopidogrel, 150 mg, once daily Period 2: * Day 1: clopidogrel, 300 mg loading dose + placebo * Day 2 to Day 5: clopidogrel, 75 mg + placebo, once daily Each intake is at around 8:00 AM fasted for at least 10 hours |
| Sequence clopidogrel 75 / 75 / 300 mg | EXPERIMENTAL | Period 1: clopidogrel 75 mg single dose Period 2: clopidogrel 75 mg single dose Period 3: clopidogrel 300 mg single dose Each intake is at around 8:00 AM under fasted conditions. |
| Name | Type | Description |
|---|---|---|
| clopidogrel (SR25990) | DRUG | oral administration (tablets) |
| ticlopidine | DRUG | oral administration (tablets) |
| Clopidogrel | DRUG | Form: reconstituted solution using Clopidogrel powder Route: oral or enteric Frequency: once daily Dose: daily dose adjusted for weight |
| placebo | DRUG | Form: reconstituted solution using matching placebo powder Route: oral or enteric Frequency: once daily Dose: daily dose adjusted for weight |
| acetylsalicyclic acid (ASA) | DRUG | oral administration |
| clopidogrel (SR25990C) | DRUG | - |
| Pantoprazole | DRUG | Pharmaceutical form: delayed-release tablet Route of administration: oral |
| Omeprazole | DRUG | Pharmaceutical form: delayed-release capsule Route of administration: oral |
| Matching placebo | DRUG | Pharmaceutical form: tablet Route of administration: oral |
Inclusion Criteria: Documented symptomatic peripheral arterial disease (one or both of the following two primary criteria must be satisfied): * Current intermittent claudication with Ankle Brachial Index (ABI) \< 0.90 * A history of intermittent claudication together with previous related interven...