E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Prophylaxis of venous thromboembolism |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 7.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10049909 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To investigate the relationship between the dose of DU-176b and the occurrence of venous thromboembolism and bleeding in patients undergoing total hip replacement surgery |
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E.2.2 | Secondary objectives of the trial |
To assess the pharmacokinetics of DU-176b and its effects on coagulation parameters. |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
Patients 18 years of age or greater scheduled for elective unilateral total hip replacement surgery (including revisions). |
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E.4 | Principal exclusion criteria |
Preoperative Exclusion Criteria: Patients that meet any of the following criteria will not be included in the study: 1. Patients previously enrolled in a DU-176b study; 2. Patients less than 18 years of age; 3. Patients with known or suspected hereditary or acquired bleeding or coagulation disorder and increased risk of thromboembolic events; 4. Patients with an increased risk of bleeding; 1. Hemorrhagic stroke, or conditions predisposing to intracranial hemorrhage (e.g., previous intracranial or intra-ocular hemorrhage or non-hemorrhagic stroke within the past three months; intracranial malignancy) 2. Systemic bleeding, gastrointestinal bleeding, or a documented ulcer within the past three months 3. History of bleeding tendencies, or any significant hematologic disease that may be associated with bleeding (e.g., thrombocytopenia (<100,000/mm3) or platelet dysfunction) within the past three months 4. Abnormal pre-operative baseline PT, (INR), aPTT or platelet count, as defined by local laboratory controls 5. Uncontrolled hypertension as defined as BP> 180/100 mmHg; 6. Patients weighing less than 50 kg (111 lbs) or weight greater than 120 kg (265 lbs); 7. Patients on long-term anticoagulants-e.g. heparin (unfractionated or low molecular weight), or have received therapeutic doses of an anticoagulant within three days prior to study treatment; require ongoing treatment with a vitamin K antagonist or concomitant use of aspirin, NSAIDs with a half-life >20 hours, proton pump inhibitors or antacids; 8. Patients with contraindications to venography such as; 1. Renal dysfunction as evidenced by creatinine (defined as >1.5 mg/dl or >132 mol/L) 2. History of allergy to iodine or radiopaque dye; 3. Inadequate pedal veins for cannulation for venography. 9. Patients with a past medical history of venous thromboembolism; 10. Patients with impaired hepatic function, as shown by any of the following; • SGOT/AST 3 times the upper limit of the reference range • SGPT/ALT 3 times the upper limit of the reference range • Alkaline phosphatase 2 times the upper limit of the reference range • Abnormal prothrombin time (>1.5 times baseline control) at study entry • Bilirubin >2 times the upper limit of reference range; 11. Spinal or epidural anesthesia with traumatic puncture or catheter placement or with prolonged bleeding from the puncture site; 12. Patients who have received any investigational drug within 1 month prior to study entry or such treatment is planned during the study period; 13. Patients with any concomitant condition, including clinically relevant cardiovascular, neurologic, endocrine, metastatic or hematological malignancy; or other major systemic disease that make implementation of the protocol or interpretation of the study results difficult; 14. Immunocompromised patients, such as patients with HIV infection; 15. Patients unlikely to comply with the protocol, (e.g., uncooperative attitude, inability to return for follow-up visits, and unlikelihood of completing the study); 16. Currently receiving treatment with any other investigational drug or experimental device; 17. Known to be pregnant (all women of childbearing potential require a negative pregnancy test [-HCG] within 6 weeks or less prior to surgery); 18. Lactating women 19. Failure to provide informed consent and HIPAA authorization (USA subjects only) prior to enrollment into the study. 20. Patients with a positive screening result for hepatitis A immunoglobulin M, hepatitis B surface antigen,, hepatitis C antibody. 21. Patients with traumatic hip fracture undergoing primary surgical treatment.
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is the incidence of confirmed venous thromboembolism. The secondary endpoint is the incidence of major bleeding. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | Yes |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |