E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated | |
MedDRA Classification |
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 is to compare the difference in pain responses between treatment with ibandronic acid vs. zoledronic acid in patients with malignancy and painful metastatic bone disease. In this study, pain response is defined as a: 25% decrease in mean pain score over a 7- day period compared to mean pain score at baseline, with no more than a 25% increase in mean analgesic consumption over the same 7-day period compared to mean Baseline analgesic consumption that persists for at least 6 weeks, as determined by the “WORST PAIN” scale of the Brief Pain Inventory (BPI). | |
E.2.2 | Secondary objectives of the trial | Efficacy: Duration of the Pain Response, length of time from baseline to initial pain response, opioid side effects, analgesic consumption, and several series of functional performance and quality of life assessments. Safety: A comparison of the safety and tolerance of ibandronic acid and zoledronic acid will be described based on spontaneous reporting of adverse events and the monitoring of clinical laboratory results. Skeletal related events (SREs), defined as fracture, the need for radiotherapy to bone, the need for surgery to bone or spinal cord compression, will be specifically and prospectively monitored for the 6-month duration of the trial. Pharmcokinetic Objectives: To evaluate by a population analysis approach the pharmacokinetics of ibandronate in the target patient population, including the influence of various covariates. | |
E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria | Histological or cytological evidence of neoplastic disease (patients with prostate cancer must have progressive neoplastic disease despite at least 3 months of hormonal therapy, defined as a rise in PSA on 3 separate occasions at least 2 weeks apart or clear evidence of new bone metastases) Presence of bone metastases documented on bone x-ray, bone scintigram, CT scan or MRI scan Mean pain score of > 5 over a 7-day Baseline period on the WORST PAIN scale of the BPI Bone pain must correspond to areas of metastases on bone x-ray, bone scintigram, CT scan or MRI scan; patients whose pain is primarily due to visceral disease (e.g., liver metastases) or to neuropathy should be excluded. It is the responsibility of the investigator to insure that each patient’s pain is primarily due to bone metastatic disease. The use of at least a weak Opioid based on the WHO analgesic ladder (Appendix 13) No change in the type of systemic anti-neoplastic therapy for at least 6 weeks prior to Baseline period Age > 18 years WHO Performance Score of 0 – 3 (patients with PS of 3 must have their score based on bone pain, not underlying neoplastic disease) Adequate renal function as evidenced by a calculated creatinine clearance > 35 mL/min by Cockroft-Gault method. Normal serum calcium level Patients or their legal representatives must be able to read, understand and provide informed consent to participate in the trial. | |
E.4 | Principal exclusion criteria | Patients with an active infection or with a fever > 38.50 C within 3 days of the first scheduled day of dosing Patients with an impending pathological fracture (erosion of at least 1/3 of the cortex by neoplastic process) Patients with known CNS or meningeal metastases Patients who have received a bisphosphonate within 3 weeks of the start of the Baseline period; however, use of bisphosphonates prior to this period IS PERMITTED Patients with known hypersensitivity to any of the components of ibandronic acid or zoledronic acid Patients with untreated esophagitis or gastric ulcers. Patients who are receiving concurrent investigational therapy or who have received investigational therapy within 30 days of the first scheduled day of dosing; investigational therapy is defined as treatment for which there is currently no regulatory authority approved indication. “Investigational therapy” DOES NOT refer to approved agents used in a clinical trial in an off-label manner, e.g., in a different dose or schedule, or in a non-approved tumor. Patients requiring systemic corticosteroid treatment in doses higher than the equivalent of 30 mg hydrocortisone per day; exceptions are topical steroids, inhalation steroids; and systemic steroids administered as prophylactic anti-emetics with chemotherapy Treatment with Strontium89 or Samarium153 within 6 months of baseline Radiotherapy to bone within 4 weeks of randomization Pre-scheduled or prophylactic radiotherapy to bone, whether administered for bone pain or not Patients with Paget’s disease of bone Patients who are pregnant or lactating Any other medical condition, including mental illness or substance abuse, deemed by the Investigator to be likely to interfere with a patient’s ability to sign informed consent, cooperate and participate in the study, or interfere with the interpretation of the results. | |
E.5 End points |
E.5.1 | Primary end point(s) | The primary endpoint for the study is a decrease in the patient's mean pain score of at least 25% compared to their mean pain score at Baseline (based over 7- day periods using the 'worst pain' Brief Pain Inventory scale). There must be no more than a 25% increase in mean analgesic consumption over the same 7-day period compared to mean Baseline analgesic consumption, and the decrease in pain must persist for at least 6 weeks. | |
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
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 | No |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | Yes |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Information not present in EudraCT |
E.7.1.1 | First administration to humans | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Information not present in EudraCT |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | Information not present in EudraCT |
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 | Information not present in EudraCT |
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 | |
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 | Last patient, last visit. | |
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | 6 |
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 | 5 |