| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Treatment of moderate to severe chronic bone pain related to metastatic cancer. |
|
| 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 | 10049038 |
| E.1.2 | Term | Metastatic bone pain |
|
| 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 analgesic efficacy of flexibly-dosed pregabalin 150-600mg/day (BID) compared with placebo, in the adjunctive treatment of subjects with cancer-induced bone pain as measured by change in the weekly mean “worst pain” score from baseline to endpoint in cancer subjects receiving pregabalin as add-on therapy to standard-of-care opioids for moderate to severe pain due to bone metastases. |
|
| E.2.2 | Secondary objectives of the trial |
| To assess the safety and tolerability of pregabalin 150-600mg/day (BID) in the same patient population. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Males/Female subjects aged ≥ 18 years
2. Females of childbearing potential must not be lactating, have a negative serum beta-HCG pregnancy test, be surgically sterile or be practicing an effective form of contraception. Acceptable methods of contraception are as follows:
a. Hormonal (oral, injectable or transdermal contraceptives).
b. Barrier method with spermicide.
c. Intrauterine device (IUD).
d. Complete abstinence may be considered acceptable, but must first be discussed on a case-by-case basis with the Pfizer Medical Director and Pfizer Clinical Monitor prior to any screening tests for the study.
3. The patient must have a malignant, solid tumor with that has been diagnosed as having metastasized to bone, and must have moderate to severe pain secondary to the bone metastasis. The patient should also be able to identify a reference site for pain, if possible, or rate their total body pain due to bone metastases if a specific lesion cannot be identified. Radiographic or scintographic confirmation of site of the painful bone metastases is required.
4. Evidence of a personally signed and dated informed consent document indicating that the subject (or a legally acceptable representative) has been informed of all pertinent aspects of the trial prior to study entry.
5. The patient’s mental status is sufficient to complete efficacy and tolerability scales and assessments.
6. Subject is willing and able to comply with scheduled visits, treatment plan, screening laboratory tests and other trial procedures.
7. Subject must have a pain score of at least 40mm on the 100mm Patient Assessment of Pain Visual Analogue Scale at Screening (Visit 1).
8. The patient has a performance status score of 0-2 (inclusive) as measured by the ECOG.
9. Life expectancy ≥ 3 months from start of the study.
10. Creatinine Clearance ≥30mL/min as calculated by the Cockcroft-Gault equation (See Protocol Appendix 2).
11. Total white blood cell count > 1500/mm3; platelet count ≥ 50 x103/mm3.
12. If applicable, stable chemotherapy treatment initiated more than one month prior to study start with the presence of significant moderate to severe pain and no signs of improvement in pain during the past month.
13. If applicable, radiotherapy or radiopharmaceutical treatment for bone metastases initiated ≥ 15 days prior to study start with the presence of significant moderate to severe pain and no signs of improvement in pain since treatment was initiated.
14. If applicable, stable bisphosphonate therapy initiated more than two months prior to study start with the presence of significant moderate to severe pain and no signs of improvement in pain during the past month.
15. If applicable, subjects taking the following stable concomitant medications but still experiencing significant pain:
a. ≥One month stable doses of TCAs, antidepressants, but still experiencing moderate to severe pain
b. ≥ 2 weeks stable doses corticosteroids, NSAIDs, paracetamol but still experiencing moderate to severe pain
c. ≥ One month stable use of hypnotics/sedatives such as zopiclone, eszopiclone, ketazolam, zolpidem, zaleplon, triazolam, or rozerem. Dosing frequency of 3-7 times/ week is considered stable
d. ≥One month stable use of benzodiazepines such as alprazolam, clonazepam, diazepam, flurazepam, lorazepam, midazolam, quazepam, triazolam, and temazepam,
e. ≥One month stable hormone or anti-hormone therapy but still experiencing moderate to severe pain and exclude those with changes in the last month
|
|
| E.4 | Principal exclusion criteria |
1. Participation in previous clinical trials for pregabalin.
2. A previous history of intolerance or hypersensitivity to pregabalin, gabapentin or drugs with similar chemical structure.
3. Participation in any other studies involving investigational or marketed products, concomitantly or within 30 days prior to screening.
4. Illiterate or unable to complete subject-rated assessment scales.
5. The patient has back pain that, in the clinical judgment of the investigator, is related to mechanical or radicular causes.
6. The patient who has undergone diagnostic or therapeutic invasive interventions (angiography, biopsy, surgery) less than 15 days prior to study start that would impact their assessment of pain at the reference pain site or area, in the opinion of the investigator.
7. Methadone, antiepileptic drugs, current gabapentin or pregabalin use, or the initiation of analgesic therapies during the trial.
8. The patient has a physical or mental inability to answer question and comply with treatment protocol (such as an inability to swallow tablets or tolerate oral medication, or intractable nausea and vomiting).
9. The patient has a history of significant alcohol, analgesic or narcotic substance abuse within 6 months prior to screening as defined by DSM-IV-TR® criteria.
10. The patient has known seizure disorders ≥ for 6 months prior to screening.
|
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| The primary efficacy endpoint is the change in the weekly mean “worst pain” score from baseline to the weekly mean “worst pain” score two weeks after the subject has reached a stable pregabalin (placebo) dose. |
|
| 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 | No |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | Yes |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | Yes |
| E.6.13.1 | Other scope of the trial description |
|
| 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) | No |
| E.7.4 | Therapeutic use (Phase IV) | Yes |
| 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 | 4 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 28 |
| 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 | 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
|
| The End of Trial in all participating countries is defined as Last Subject, Last Visit. |
|
| 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 | 4 |
| E.8.9.1 | In the Member State concerned days | 0 |
| 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 | 4 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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