E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Adjunctive treatment for the management of post-operative pain |
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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 | 10036236 |
E.1.2 | Term | Postoperative pain relief |
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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 |
The primary objective of this study is to assess the efficacy of pregabalin compared to placebo on pain following hysterectomy, measured using subject reported assessments of pain. |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives of this study (18 of them) are listed in the protocol. For all secondary objectives please refer to the protocol. Listed below are three of the secondary objectives. Please note that the secondary objectives are not ranked according to significance, but a limited list is presented here due to lack of characters allowed in this field;
1. Evaluate the effect of pregabalin on pain with movement (specifically assessed in this protocol as pain with sitting and at peak expiratory flow, PEF) following surgery. (NRS Current Pain). 2. Evaluate the opioid-sparing effect of pregabalin compared to placebo when administered for the treatment of post-surgical pain following hysterectomy. 3. Evaluate the effect of pregabalin compared to placebo on the occurrence of opioid-related symptoms as assessed using the Opioid-Related Symptom Distress Scale (OR SDS).
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Subjects must meet all of the following inclusion criteria to be eligible for enrollment into the trial: 1. The subject is between the ages of 25-70 years old. 2. The subject (or legally acceptable representative) has provided written informed consent that must be obtained prior to admission to this study. 3. Females of childbearing potential must have a negative serum β-HCG pregnancy test at screening and negative urine pregnancy test at hospital admission. 4. The subject will have elective abdominal hysterectomy using a transverse incision with or ithout bilateral salpingo-oophorectomy. The hysterectomy may be cervix-sparing. 5. The subject will either be admitted the evening before the day of surgery or will come for visit to be randomized and receive study medication prior to the day of surgery. 6. The subject is expected to remain at the hospital (or intermediate care facility) for a minimum of 2 days following surgery. 7. The subject is expected to require supplemental analgesic treatment of post-operative pain for at least 2 full days. 8. The subject’s preoperative health is graded as ASA P1 to P2. 9. The subject is in satisfactory health as determined by the investigator on the basis of medical history, physical examination and laboratory results.
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E.4 | Principal exclusion criteria |
1. Subjects having vaginal hysterectomy (whether laparascopically assisted or not) 2. Subjects having additional procedures (such as those involving the bladder) at the same ime as the abdominal hysterectomy. However, cosmetic modification of a scar at the same ncision site (eg, from previous Cesarean section) is permitted. 3. The use of nerve block, spinal anesthesia or epidural anesthesia for post-surgical pain control. 4. Subjects who have been using any opioid medications 2 weeks or more continuously within 3 months prior to the screening visit. 5. The subject has any cognitive impairment that would, in the investigator’s opinion, preclude study participation or compliance with protocol mandated procedures. 6. The subject has a history of known alcohol, analgesic, or narcotic substance abuse (according to DSM-IV criteria) within 12 months prior to Screening. 7. The subject has a history of clinically significant intolerance or hypersensitivity to pregabalin, and/or any analgesic which has a cross sensitivity to the medications used in this study. 8. Use of prohibited medications as listed in the protocol in the absence of appropriate washout phase or the likelihood of requiring treatment during the study period with drugs not permitted by the study protocol. 9. The subject has a history of cerebrovascular accident, transient ischemic attack, myocardial infarction, unstable myocardial ischemia (angina), deep venous thrombosis or pulmonary embolism within three months of surgery. 10. The subject has taken any NSAID or any analgesic other than acetaminophen within 3 days prior to surgery or is unwilling to abstain from NSAIDs or other analgesics, except as specified in the protocol, during the study. (Subjects taking ≤325 mg per day of aspirin at a stable dose for at least 30 days before the first dose of study medication will be allowed to continue their aspirin regimen for the duration of the study). 11. The subject has a history of uncontrolled chronic disease that, in the opinion of the investigator, would contraindicate study participation or confound interpretation of results. Examples include chronic pain conditions such as post-herpetic neuralgia, painful diabetic peripheral neuropathy, and fibromyalgia as well as chronic neurologic disorders such as stroke, Parkinson’s Disease or Multiple Sclerosis. 12. Subjects having a history of endometriosis (unless one of the following are met): A.The Investigator determines that the endometriosis will not confound the subjects assessment of pain post-surgically.B. The subject has not required analgesic treatment for endometriosis in the prior month. 13. The subject’s preoperative health is graded as ASA P3 or higher. 14. The subject currently has or has been treated for cancer (ie. surgery, chemotherapy, radiation therapy, etc.) and/or has been in remission for any cancer other than basal cell carcinoma or squamous cell carcinoma for less than 2 years prior to screening. 15. The subject has received pregabalin within 30 days prior to the screening visit is scheduled to receive any investigational drug during the course of this study. 16. Any clinically significant or unstable medical or laboratory abnormality that, in the opinion of the investigator, would compromise participation in the study such as: a. Significant renal disease, including • Creatinine clearance < 60 ml/min (estimated from serum creatinine, body weight, age, and sex using the Cockcroft-Gault equation) b. Significant hepatic disease c. Significant respiratory disorder d. Significant hematologic disorders, including • Total white blood cell count < 2500/mm3 • Platelet count < 100 x 103/mm3 e. Significant immunologic diseases f. Unstable cardiovascular disease g. Significant inflammatory or rheumatologic diseases h. Active hepatitis B or C, HIV infection, or other significant infectious condition diagnosed within the past 3 months. i. Symptomatic peripheral vascular disease j. Untreated endocrine disorders 17. Expected to require analgesics or other agents other than as specified in the protocol from the end of surgery through the end of the treatment period, that could confound the analgesic responses (a longer interval may be necessary if the confounding drug is long-acting or a sustained-release formulation). Specifically excluded are tricyclic antidepressants, tranquilizers, neuroleptics, neuroleptic antiemetics, COX-2 inhibitors, other NSAIDs (with the exception of naproxen, ibuprophen, or ketoprophen used as second line rescue medication), and corticosteroids. Subjects receiving aspirin for antithrombotic prophylaxis at doses ≤325 mg/day are permitted to continue this treatment. Subjects receiving Selective Serotonin Reuptake Inhibitors (SSRIs) at stable doses from 4 weeks prior to surgery through the duration of the study will be allowed. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is the pain reported by subjects, using the NRS-Worst Pain on the first day (approximately 24 hours) after the surgery.
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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 | No |
E.6.7 | Pharmacodynamic | No |
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 | 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 | 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) | 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
| Information not present in EudraCT |
E.8.4 | The trial involves multiple sites in the Member State concerned | Information not present in EudraCT |
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 | 13 |
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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Follow-up phone calls are part of the trial, so the end is after the second (6 months post end of treatment +/- 10 days) of these.
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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 | 1 |
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 | 1 |
E.8.9.2 | In all countries concerned by the trial months | 7 |
E.8.9.2 | In all countries concerned by the trial days | 0 |