E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Prevention of bone metastases in men with prostate cancer
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10005993 |
E.1.2 | Term | Bone metastases |
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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 assess the effect of treatment with MK-0822 5 mg once daily on bone metastasis-free survival (defined as time to first bone metastasis or death from any cause) compared to placebo. • To assess the effect of treatment with MK-0822 5 mg once daily in a subset of 300 patients on lumbar spine, total hip, femoral neck, trochanter and total body bone mineral density (BMD) compared to placebo. • To assess the tolerability of treatment with MK-0822 5 mg once daily compared to placebo. |
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E.2.2 | Secondary objectives of the trial |
• To assess the effect of treatment with MK-0822 5 mg once daily on the risk of developing bone metastases compared to placebo. • To assess the effect of treatment with MK-0822 5 mg once daily on the risk of death from any cause compared to placebo. • To assess the effect of treatment with MK-0822 5 mg daily on biochemical markers of bone turnover compared to placebo. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Patient is a man ≥18 years of age on the day of signing the informed consent. • Patient has hormone-refractory (androgen-independent) prostate cancer, defined as 3 rising, consecutive, historical PSA values following bilateral orchiectomy, or while receiving continuous (not intermittent) androgen-deprivation therapy. The second and third historical PSA tests (i.e., values obtained prior to the screening visit) must be separated from the previous test by at least 2 weeks, and the second and third values must each be ≥ 1.0 ng/mL. • Patient has a serum testosterone <50 ng/dL at screening. • Patient is at increased risk for prostate cancer progression defined as either an elevated PSA of ≥8 ng/mL obtained at the screening visit as measured by the central laboratory, or a PSA doubling time (PSADT) of ≤10 months (defined as ≤ 300 days). • Patient underwent bilateral orchiectomy 3 months or more (i.e., ≥90 days) prior to Visit 1, or is receiving androgen-deprivation therapy (ADT) and is on a stable GnRH agonist regimen for at least 3 months (i.e., ≥90 days) prior to Visit 1. ADT cannot be modified between Visit 1 and Visit 2 (the randomization visit). Androgen-deprivation therapy may include gonadotropin-releasing hormone agonists (GnRH) such as leuprolide, goserelin, or triptorelin. Patients receiving anti-androgen (e.g., flutamide, bicalutamide, nilutamide) monotherapy are not eligible, however, patients receiving an anti-androgen in combination with androgen deprivation (with a GnRH agonist or bilateral orchiectomy) are eligible, and in this case these therapies cannot be modified between Visit 1 and Visit 2. Patients who have failed anti-androgen monotherapy in the past, and are now failing androgen deprivation (with a GnRH agonist or bilateral orchiectomy) are also eligible. • Patient has not undergone radiotherapy, OR if patient has undergone radiotherapy he has recovered and is at least 4 weeks from the previous radiotherapy at the time of screening (Visit 1). |
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E.4 | Principal exclusion criteria |
• Patient has bone metastases, or has a history of bone metastases: patient must have a negative bone scan obtained during the screening period, or within 1 month prior to the screening visit (Visit 1). All bone scans and associated imaging studies used for eligibility purposes must be adjudicated by the central radiologist before the patient may be randomized at Visit 2. • Patient has other distant metastases (e.g., visceral, including brain, or soft-tissue). Patients with regional lymph nodal metastases are eligible. • Patient has ANY of the following: a) is currently receiving a bisphosphonate (e.g., etidronate, clodronate, tiludronate, pamidronate, alendronate, ibandronate, risedronate, olpadronate, neridronate, zoledronate), or other drug therapy for osteoporosis; b) has been treated with an oral bisphosphonate within the 6 months prior to Visit 1; c) has been treated with an intravenous bisphosphonate within the 12 months prior to Visit 1. • Patient has received chemotherapy within the 2 years prior to Visit 1 (for example, doxorubicin, cyclophosphamide, estramustine, paclitaxel, docetaxel, etoposide, vinblastine, 5-fluorouracil, interferon, mitoxantrone). Patients may not start chemotherapy between Visit 1 and Visit 2. This exclusion criterion does not include androgen-deprivation therapy, which is permitted and expected in patients entering this study (e.g., gonadotropin-releasing hormone agonists such as leuprolide, goserelin, or triptorelin). • Patient is using any of the following potent inhibitors of CYP3A4 within 2 weeks prior to starting blinded study medication: (a) systemically administered azole antifungals such as ketoconazole, fluconazole, itraconazole, miconazole, posaconozole, ravuconazole, and voriconazole; (b) nefazodone; (c) the macrolide antibiotics clarithromycin, dirithromycin, erythromycin, and troleandomycin, however, azithromycin, is permitted. The use of any other macrolide antibiotic requires approval by the SPONSOR’s clinical representative. Patients who discontinue these medications at least two weeks prior to starting blinded study medication are eligible. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Time to First Bone Metastases Death |
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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 | 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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
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) | No |
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 | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 90 |
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 | Yes |
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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When the required number of primary endpoints has accrued. This is an event driven 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 | 3 |
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 | 3 |
E.8.9.2 | In all countries concerned by the trial months | 6 |