E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Prevention of venous thromboembolism (VTE) after total hip replacement
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 8.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10049909 |
E.1.2 | Term | Venous thromboembolism prophylaxis |
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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 |
The primary objective of this study is to assess the efficacy of DU-176b in the prevention of venous thromboembolism (VTE). |
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E.2.2 | Secondary objectives of the trial |
To compare the incidence of VTE and major and clinically relevant non-major bleeds of DU-176b to dalteparin and
To assess the pharmacokinetic (PK) and pharmacodynamic (PD) properties of DU-176b.
Assessment of all bleeding events, treatment-emergent adverse events (TEAEs), laboratory test values, vital signs, and electrocardiograms (ECGs) in the DU-176b and the dalteparin treatment groups. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Subjects must meet all of the following criteria for inclusion in the study:
18 years of age or older; male or female.
Able to provide written informed consent.
Must be scheduled for elective unilateral total hip replacement surgery. Only primary surgeries accepted.
If female, must be either one year post-menopausal, surgically sterile, or using medically accepted contraceptive measures as judged by the Investigator and in accordance with local regulatory requirements.
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E.4 | Principal exclusion criteria |
Subjects who meet any of the following preoperative exclusion criteria will be excluded from the study:
Cancelled hip replacement surgery.
Subjects with traumatic hip fracture undergoing primary surgical treatment.
Subjects with known or suspected hereditary or acquired bleeding or coagulation disorder or at increased risk for thromboembolic events (eg, subject with past medical history of VTE).
Subjects with an increased risk of bleeding. - Hemorrhagic stroke or conditions predisposing to intracranial hemorrhage (eg, previous intra-ocular hemorrhage or non-hemorrhagic stroke within the past 3 months, intracranial malignancy). - Gastrointestinal bleeding or a documented ulcer within the past 3 months. - Abnormal preoperative baseline PT or aPTT.
Uncontrolled hypertension defined as systolic blood pressure (BP)>180 mmHg and/or diastolic BP>110 mmHg.
Subjects on long-term oral anticoagulants (vitamin K antagonist) or who have received therapeutic doses of an anticoagulant or fibrinolytic agent within 10 days prior to study treatment.
Subjects requiring ongoing treatment with an anti-platelet agent, including nonsteroidal anti-inflammatory drugs (NSAIDs), aspirin (>100 mg/day excluded), clopidogrel, ticlopidine, and dipyridamole.
Subjects with a hypersensitivity to dalteparin, heparin, or pork products.
Subjects with contraindications to venography including: - Renal dysfunction defined as serum creatinine >132 µmol/L - History of allergy to iodine or radiopaque dye - Inadequate dorsal pedal veins for cannulation for the venography procedure
Subjects with anemia defined as hemoglobin (Hgb) <90 g/L or thrombocytopenia defined as platelet count <100 × 109/L.
Subjects with impaired hepatic function, as shown by any of the following: - AST ≥ 1.5 times the upper limit of the reference range - ALT ≥ 1.5 times the upper limit of the reference range - Bilirubin ≥ 1.5 times the upper limit of the reference range - Gamma glutamyl transpeptidase (GGT) ≥ two times the upper limit of the reference range
Subjects with positive Hepatitis A, B, or C serology.
Subjects with a known drug or alcohol dependence within the past 12 months as defined by the Investigator.
Subjects known to be pregnant or lactating.
Subjects unable to complete the study requirements due to a clinically relevant concomitant disease as defined by the Investigator.
Subjects with a disease that gives an estimated life survival of less than 12 months as judged by the Investigator.
Subjects who have received an investigational drug within one month prior to study entry or are planning any such treatment.
Subjects previously enrolled in a DU-176b study.
Subjects unlikely to comply with the protocol (eg, uncooperative attitude, inability to return for follow-up visits, and unlikely to complete the study).
Subjects with prior knee replacement surgery.
Subjects will be assessed post-operatively for the following exclusion criteria and will be ineligible for this study if any of these additional criteria are met:
Require the use of an indwelling epidural catheter for analgesia post operatively.
Received spinal or epidural anesthesia and spinal tap was traumatic or bloody.
Unusual or excessive bleeding either during the operation or in the immediate postoperative period based on the clinical judgment of the Investigator.
Inability to take anything by mouth for greater than 8 hours post surgery.
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is the incidence of confirmed VTE.
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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 | No |
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 | No |
E.6.10 | Pharmacogenetic | No |
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 | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
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) | Yes |
E.8.2.2 | Placebo | Yes |
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.8.4.1 | Number of sites anticipated in Member State concerned | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 22 |
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 | No |
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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The end of the study will be defined as the date of the last visit of the last subject in the study. |
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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 | 1 |
E.8.9.1 | In the Member State concerned months | 7 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 7 |