E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Moderate to severe chronic pain |
|
MedDRA Classification |
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 efficacy and tolerability of a titrated divisible buprenorphine transdermal patch in comparison to non-titrated buprenorphine transdermal patch over 4 weeks in opioid naïve patients with moderate to severe chronic non-malignant pain |
|
E.2.2 | Secondary objectives of the trial |
- Incidence of adverse events - Time to withdrawal due to adverse events or lack of efficacy - Frequency and intensity of adverse events - Twice daily assessments of current pain intensity using an 11-point Numerical Rating Scale (NRS). - Twice daily assessments of average pain intensity in the last 24 hours using an 11-point Numerical Rating Scale (NRS). - Amount and frequency of intake of rescue medication - Patient's global evaluation using a 5-point verbal rating scale (VRS) - Sleep questionnaire using the Chronic Pain Sleep Inventory (CPSI) |
|
E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
- At least 18 years of age at enrolment - Subjects suffering from chronic non-malignant pain (of at least 3 months duration) - Subjects with pain intensity of at least 5 on an 11-point NRS and requiring an equianalgesic dose range equivalent to 30 - 60 mg oral morphine per day - Subjectsts taking ≤ 325 mg acetylsalicylic acid (ASA) daily for cardiovascular prophylaxis who have been on a stable dose for ≥ 30 days may be enrolled - Males or non-pregnant, non-lactating, or postmenopausal females. Female patients of childbearing potential must use an acceptable method of contraception (e.g., prescription oral contraceptives, contraceptive injections, intrauterine device, double-barrier method, contraceptive patch, male partner sterilization) during study period and have a negative urine pregnancy test (at screening). - Expected course of the disease and the pain that will permit compliance with the study protocol over the entire study period - The patient has been informed about the nature of the study, understood the information and given written informed consent before undergoing any study procedures |
|
E.4 | Principal exclusion criteria |
- Participation in another study parallel to or less than 30 days before study entry - Alcohol and/or drug abuse in the investigator’s judgment, based on patient history and physical examination - Positive urine test for drugs of abuse, other than prescription analgesic substances for a medical condition - Subjects with respiratory depression in the absence of resuscitative equipment, and in patients with severely impaired respiratory centre/function, and in any patient who has or is suspected of having a paralytic ileus - Subjects who are opioid tolerant, or have used opioids for any indication within 3 months of study start, who have ever used opioids for longer than 6 months - Previous and/or current unhealed extensive dermal damage in the area where the patch is to be applied (e.g., dermatitis, burns, scarring of the skin) - Known hypersensitivity to any of the study medications, i.e., the active substance buprenorphine or to any of the excipients - Any scheduled surgery and/or painful procedure during the course of the study - History of seizure disorder, dementia and history of head trauma requiring evaluation by hospital based staff, or unconsciousness of unknown origin - Intake of adjuvant analgesics (e.g. antidepressants, anticonvulsants, selective serotonin reuptake inhibitors [SSRIs], serotonin-norepinephrine reuptake inhibitors [SNRIs], muscle relaxants, bisphosphonates, corticosteroids, phytopharmaceutics), antiparkinsonian drugs, neuroleptics or laxatives if not on a stable dose within 30 days prior to the screening visit - Concomitant intake and/or intake within 30 days prior to the screening visit of monoamine oxidase (MAO) inhibitors or anti-emetics - TENS (transcutaneous electrical nerve stimulation), physiotherapy, acupuncture, and other adjunctive therapy if procedures are not stable, ie, performed at the same ferquency, within 30 days prior to the screening visit - Patients suffering from myasthenia gravis |
|
E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint will be a comparison for non inferiority of the titrated divisible buprenorphine transdermal patch versus the buprenorphine transdermal patch Transtec® PRO based on baseline adjusted mean pain intensity at Visit 5 (Day 27-29). Pain in the last 24 hours will be used for evaluation of the primary endpoint. |
|
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 | Information not present in EudraCT |
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 | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
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) | Yes |
E.8.2.2 | Placebo | No |
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.8.5 | The trial involves multiple Member States | Yes |
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 | Information not present in EudraCT |
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
|
Follow-up visit (last visit) of the last subject |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
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 months | 6 |