E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
progressive castration-resistant prostate cancer. |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 16.1 |
E.1.2 | Level | SOC |
E.1.2 | Classification code | 10029104 |
E.1.2 | Term | Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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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 determine whether orteronel 300 mg twice daily (BID) plus prednisone 5 mg BID more effectively reduces serum testosterone levels, compared to placebo plus prednisone 5 mg BID, when administered to patients in Japan |
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E.2.2 | Secondary objectives of the trial |
•To evaluate the reduction in serum testosterone levels in ex-Japan patients administered orteronel 400 mg BID plus prednisone 5 mg BID, when compared to placebo plus prednisone 5 mg BID
•To determine whether orteronel plus prednisone improves 50% prostate-specific antigen (PSA) response
•To evaluate the effect of orteronel plus prednisone on endocrine markers of pharmacodynamic response
•To characterize the pharmacokinetics of orteronel plus prednisone
•To continue to assess the safety of orteronel plus prednisone in patients with castration resistant prostate cancer (CRPC)
Exploratory
•To explore the pharmacokinetic (PK) -pharmacodynamic response to orteronel plus prednisone in patients in Japan and ex-Japan
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1.Male patients 18 years or older.
2.Voluntary written consent must be given before performance of any study-related procedure not part of standard medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to future medical care.
3.Histologically or cytologically confirmed diagnosis of prostate adenocarcinoma.
4.Prior surgical castration or concurrent use of an agent for medical castration (eg, GnRH analogue).
5. PSA ≥ 2 ng/mL at screening.
6. Progressive disease based on PSA/and or radiographic criteria |
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E.4 | Principal exclusion criteria |
1.Prior therapy with orteronel, ketoconazole, aminoglutethimide, or abiraterone.
2.Known hypersensitivity to compounds related to orteronel, orteronel excipients, prednisone (or commercially available equivalent), or GnRH analogue.
3.All antiandrogen therapy (including bicalutamide) is excluded within 4 weeks before the first dose of study drug. Any other therapies for prostate cancer, other than GnRH analogue therapy, such as progesterone, medroxyprogesterone, progestins (megesterol), or 5-alpha reductase inhibitors (eg, finasteride or dutasteride), must be discontinued 2 weeks before the first dose of study drug.
4.Continuous daily use of oral prednisone (or commercially available equivalent), oral dexamethasone, or other systemic corticosteroids for more than 2 weeks within the 3 months before screening (inhaled, nasal, and local steroids [eg, joint injection] are allowed).
5.Prior chemotherapy for prostate cancer, with the exception of neoadjuvant/adjuvant therapy as part of initial primary treatment for local disease that was completed 2 or more years before screening.
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E.5 End points |
E.5.1 | Primary end point(s) |
Percentage of patients in Japan with serum testosterone levels reduced to ≤ 2 ng/dL after 4 weeks of treatment with orteronel 300 mg BID plus prednisone 5 mg BID, when compared to placebo plus prednisone 5 mg BID |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Cycle 1 Day 1 through Cycle 2 Day 1 [study Day 29 +/- 1 day] |
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E.5.2 | Secondary end point(s) |
•Percentage of ex-Japan patients with serum testosterone levels reduced to ≤ 2 ng/dL after 4 weeks of treatment with orteronel 400 mg BID plus prednisone 5 mg BID, when compared to placebo plus prednisone 5 mg BID
•Serum testosterone levels after 4 weeks of treatment with study drug (orteronel plus prednisone or placebo plus prednisone) and after 12 weeks of active treatment with orteronel plus prednisone in all treatment groups
•PSA reduction ≥ 50% after 4 weeks of treatment with study drug (orteronel plus prednisone or placebo plus prednisone) and after 12 weeks of active treatment with orteronel plus prednisone in all treatment groups
•Pharmacodynamic effects of orteronel as measured by endocrine markers dehydroepiandrosterone sulfate (DHEA-S), ACTH, corticosterone, and cortisol in all treatment groups
•PK parameters, including, but not limited to, Cmax, AUC from zero to 24 hours (AUC24hr), AUCinf, single dose first time of occurrence of maximum (peak) concentration (Tmax), and the cumulative amount of unchanged drug excreted into the urine (Ae) in all treatment groups
•Adverse events (AEs), serious adverse events (SAEs), assessments of clinical laboratory values, vital sign measurements, physical examination findings, and electrocardiograms (ECGs) in all treatment groups
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Cycle 1 Day 1 through Cycle 2 Day 1 [study Day 29 +/- 1 day] |
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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 | No |
E.6.3 | Therapy | Yes |
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) | Yes |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | Yes |
E.7.1.3.1 | Other trial type description |
Pharmacokinetics and Pharmacodynamics |
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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 | 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 | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
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 | 1 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 29 |
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 | No |
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 |
Greece |
Ireland |
Italy |
Japan |
Austria |
Netherlands |
New Zealand |
Portugal |
Australia |
Germany |
United Kingdom |
United States |
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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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Treatment will be considered complete when the required PK pharmacodynamic assessment period of a minimum of 12 weeks of active treatment with orteronel is complete (16 weeks for patients receiving orteronel or 12 weeks for patients receiving placebo). Patients may then remain on treatment and be assessed as clinically indicated at the discretion of the investigator according to standard of care until treatment with study drug is discontinued. |
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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 | 10 |
E.8.9.1 | In the Member State concerned days | 0 |
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 | 11 |
E.8.9.2 | In all countries concerned by the trial days | 0 |