A study to investigate whether the administration of flupirtine in combination with opioids is safe, tolerable and efficacious when administered to cancer patients who are suffering from pain that shows neuropathic characteristics
- Conditions
- Pain with neuropathic features in cancer subjects which is inadequately controlled despite optimized opioid treatmentMedDRA version: 14.0Level: LLTClassification code 10045158Term: Tumor painSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Symptoms and general pathology [C23]
- Registration Number
- EUCTR2011-001202-99-DE
- Lead Sponsor
- Relevare Pharmaceuticals, Ltd.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 300
1. Presence of a solid neoplasm and between the ages of 18 and 65 years, inclusive
2. Able to understand written and verbal communication in the primary language of the country in which the study is being undertaken
3. Life expectancy a minimum of 3 months with Karnofsky score =50 at the Screening Visit (Day -7)
4. History of daily pain attributable to cancer and requiring treatment with strong opioids for at least 3 months duration
5. Pain with neuropathic characteristics that include one or more of the following: throbbing, shooting, stabbing, sharp, cramping, gnawing, hot-burning, aching, heavy, tender, splitting, tiring-exhausting, sickening, fearful, punishing-cruel, electric-shock, cold-freezing, piercing, caused by light touch, itching, tingling or ‘pins and needles’, or numbness.
6. Pain inadequately relieved despite active management including strong opioids
7. Currently taking morphine, oxycodone, hydromorphone, buprenorphine, or transdermal fentanyl for daily, non-breakthrough pain management (i.e., maintenance opioid treatment) with no changes in dose in the 2 weeks preceding the Screening Visit (Day -7)
8. Completion of a daily diary in which the 24-hour AP score has been entered for at least 5 of the last 7 days preceding Day 1
9. Average of non-missing 24-hour AP scores over the last 7 days before the day of randomization is 4 or greater
10. If on gabapentin, pregabalin or selective serotonin reuptake inhibitors (SSRIs) or tricyclic antidepressants, no changes in dose in the 2 weeks preceding the Screening Visit (Day -7)
11. Willing to maintain existing analgesic medications, including maintenance opioid treatment, at same dose(s) and schedule for a minimum of 6 weeks following the Screening Visit (Day -7)
12. Able to take oral medication
13. If female subject of childbearing potential, a negative serum beta human chorionic gonadotropin (hCG) pregnancy test, performed at the Screening Visit (Day -7). Must be willing to use effective methods of birth control and/or refrain from participating in a conception process during the study and for 30 days following study drug exposure.
14. Willing and able to comply with protocol requirements for the duration of study participation
15. Contractual capability and signed informed consent
Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 280
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 20
1. Medical condition or illness other than solid neoplasm that would, in the opinion of the Investigator, preclude study participation or interfere with the assessment of pain
2. Abnormal liver or kidney function as defined by alanine aminotransferase (ALT), aspartate aminotransferase (AST) or alkaline phosphatase in excess of 3 times the upper limit of normal, or chronic kidney disease worse than stage II (glomerular filtration rate <60 mL/min as calculated by Cockroft-Gault formula [(140-age) x (weight in kilograms) x (0.85 if female) / (72 x serum creatinine in mg/dl)])
3. Significant pain with neuropathic features which cannot be attributed to underlying malignancy
4. Proven hypersensitivity to flupirtine or one of the other ingredients
5. Cholestasis, pre-existing liver disease, or at risk of hepatic encephalopathy
6. Use of paracetamol-containing medications or carbamazepine
7. History of radiotherapy or a nerve block or other anesthetic procedure to the presumed site of nerve damage within 4 weeks preceding the Screening Visit (Day -7). Such procedures after the Screening Visit will necessitate withdrawal from the study.
8. If receiving a bisphosphonate medication, change in dose or frequency within 3 months preceding the Screening Visit (Day -7)
9. If receiving a hormonal contraceptive, change in dose or frequency within 3 months preceding the Screening Visit (Day -7)
10. Systemic radioisotope therapy within 1 month preceding the Screening Visit (Day-7)
11. Significant history of illicit drug or alcohol abuse
12. Current or previous (within 30 days of first study dosing) treatment with another investigational drug or participation in another clinical study
13. Change in chemotherapy regimen anticipated within 6 weeks following the Screening Visit
14. Pregnant or lactating females. Serum pregnancy test must be performed within 7 days prior to study treatment start, or within 14 days with a confirmatory urine pregnancy test within 7 days prior to study treatment start;
15. Known hepatitis B or C or HIV infection
16. Not suitable for study participation in the Investigator’s judgment
17. Previous participation in this study
18. Patient is a relative of, or staff directly reporting to the Investigator
19. Patient is an employee of the sponsor
20. Subject is committed under official or judicial order
21. Patient with a known diagnosis of myasthenia gravis
22. Patient with a known diagnosis of tinitus
23. Patients with metastatic liver disease (accompanied by change in LFTs to >2x ULN)
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: The primary objective of this study is to explore the overall analgesic efficacy of flupirtine administered in combination with opioids for a period of 5 weeks.;Secondary Objective: Secondary objectives of this study are to:<br>- Investigate the safety and tolerability of flupirtine administered in combination with opioids; <br>- Investigate the efficacy of flupirtine using various secondary measures of efficacy. <br>;Primary end point(s): Change in the 11-point Likert scale for average daily pain from the baseline mean pain score (the mean of non-missing daily diary entries for average pain during the 7 days before randomization) to the final mean pain score (the mean of last 7 daily diary entries for average pain during the Treatment Period);Timepoint(s) of evaluation of this end point: Day 36 visit
- Secondary Outcome Measures
Name Time Method Secondary end point(s): - Percentage of subjects achieving at least 30% improvement from baseline based on the primary efficacy endpoint;<br>- Physician and Subject Global Assessment of study drug;<br>- Change in the 11-point Likert scale from the baseline mean pain score to the mean pain score during each week of the Treatment Period; <br>- Percentage of subjects achieving pre-specified pain reduction thresholds (e.g., 20% to 100%); and<br>- Opioid consumption, BPI (short-form), average pain the past 24 hours, least pain in past 24 hours, and worst pain in past 24 hours.<br>;Timepoint(s) of evaluation of this end point: Day 36 visit