E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
metastatic castration-resistant prostate cancer (mCRPC) |
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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 | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10036909 |
E.1.2 | Term | Prostate cancer metastatic |
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 evaluate the effects of orteronel, when administered with prednisone, on the QT/QTc interval in patients with metastatic castration-resistant prostate cancer (mCRPC) |
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E.2.2 | Secondary objectives of the trial |
To continue to assess the safety and pharmacokinetics of orteronel, when administered with prednisone, in patients with mCRPC |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Voluntary written consent.
2. Patients must have a diagnosis of mCRPC.
3. Screening PSA ≥ 2 ng/mL.
4. Prior surgical or medical castration with testosterone at screening < 50 ng/dL.
5. Eastern Cooperative Oncology Group performance status of 0 or 1.
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E.4 | Principal exclusion criteria |
1. Prior chemotherapy for prostate cancer within 6 months prior to screening. (Any prior therapy with cabazitaxel, mitoxantrone, or anthracyclines is exclusionary.).
2. Documented central nervous system metastases.
3. Clinically significant heart disease.
4. Patients who have an abnormal 12-lead ECG result at screening including one or more of the following: QRS>110 ms, QTcF>480ms, PR interval>200 ms
5. Patients who have a history of risk factors for TdP including unexplained syncope, known long QT syndrome, heart failure, angina, or clinically significant abnormal laboratory assessments.
Please note that there are additional inclusion and exclusion criteria. The study center will determine if you meet all of the criteria.
Site personnel will explain the trial in detail and answer any question you may have if you do qualify for the study. You can then decide whether or not you wish to participate. If you do not qualify for the trial, site personnel will explain the reasons
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is the change from baseline in QTc, based on the QTc with Fridericia correction (QTcF) method |
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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) |
The secondary endpoints include:
- Change from baseline in QTc with Bazett correction (QTcB), PR and QRS intervals, and uncorrected QT interval
-Change from baseline in HR
-Change from baseline in ECG morphology
-PK parameters for orteronel, including AUC from 0 to 6 hours (AUC0-6hr), Cmax, and first time to maximum plasma concentration (Tmax)
-Correlation between the QTcF change from baseline and plasma concentrations of orteronel
-Rates of AEs and serious adverse events (SAEs), changes in clinical laboratory values, vital sign measurements, physical examination findings, and ECG results |
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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 | Yes |
E.6.12 | Pharmacoeconomic | Yes |
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 | No |
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.8.2.4 | 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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 11 |
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 |
Canada |
France |
Greece |
Ireland |
Romania |
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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The end of the trial is defined as when the last patient completes the required QT/QTc assessment period (ie, Cycle 1 Day 1 though Cycle 2, Day 1 [study Day 29 +/- 1 day]. After completing the required QT/QTc assessment period (ie, Cycle 1, Day 1 through Cycle 2, Day 1 [study Day 29 ± 1 day]), patients may remain on treatment at the discretion of the investigator.
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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 | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |