E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Diabetic peripheral neuropathic pain |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10067547 |
E.1.2 | Term | Diabetic peripheral neuropathic pain |
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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 assess the efficacy of SAR407899A administered at 15 mg twice daily for 28 days in comparison to placebo in reducing pain intensity in patients with painful diabetic neuropathy as measured on the 11 point numerical rating scale (NRS). |
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E.2.2 | Secondary objectives of the trial |
To investigate the safety and tolerability of 15 mg SAR407899A twice daily in comparison to placebo.
To compare the effects of SAR407899A with placebo on the change of pain intensity versus baseline by using the following scales and clinical tests: - The Visual Analog Scale Pain Intensity Scale, - The Visual Analog Scale Pain Relief Scale, - The Neuropathic Pain Symptom Inventory.
To evaluate the effects of SAR407899A in comparison to placebo on the change in pain intensity of mechanical allodynia.
To evaluate the use of rescue medication (paracetamol) in SAR407899A-treated patients in comparison to placebo-treated patients.
To assess the exposure to SAR407899A. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Patients with painful diabetic neuropathy The neuropathic pain must have a distinct, neuroanatomically plausible distribution demonstrated by at least one confirmatory test (e.g., clinical sensory examination, electrophysiology);
2. Having given written informed consent prior to any procedure related to the study.
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E.4 | Principal exclusion criteria |
Related to study metho 1. Patients < 18 years or ≥ 70 years of age; 2. Average daily pain intensity for neuropathic pain < 4 on the 11-point NRS over the last 3 days before rando; 3. Patients in whom the time between diagnosis of diabetic neuropathy and study start is < 6 mths; 4. Patients with HbA1c > 10 %; 5. Patients with history of hypoglycaemia unawareness; 6. Patients with a history of hypoglycaemia with unconsciousness during the last 3 mths prior to the study, ketoacidosis, hyperosmolar coma, major changes in diabetes therapy 7. Patients with any conditions other than the diabetic neuropathic pain that cause pain of equal or greater severity; 8. Patients with abnormal folate and/or vitamin B12 that could be the cause of the neuropathic pain, and need to be corrected; 9. Patients with hypothyreosis as shown by elevated TSH; 10. Patients receiving analgesic medication for conditions other than diabetic neuropathic pain; 11. Patients with previous treatment failure to > 2 approved treatment regimens for neuropathic pain of adequate doses and duration; 12. Patients not willing to washout of all analgesic medications prior to the start of study treatment (except paracetamol/acetaminophen); 13. Patients with severe or unstable hepatic, gastrointestinal, cardiovascular, respiratory, neurological psychiatric, hematological, renal, dermatological disease, progressive malignancy, hepatobiliary disease or any other medical condition that might interfere with the evaluation of study medication according to investigator’s medical judgment; 14. Laboratory parameters outside the normal range unless the investigator considers an abnormality as clinically not relevant for these patients; 15. Patients with contraindications for paracetamol treatment 16. Creatinine clearance < 60 mL/min; 17. Presence of significant abnormalities on a standard electrocardiogram recording at the screening visit according to investigator’s medical judgment (e.g., QTc ≥ 500 ms); 18. Patients with uncontrolled hypertension defined as systolic blood pressure > 160 mmHg and/or diastolic blood pressure > 100 mmHg at screening; if on antihypertensive treatment: treatment should have been stable during the last 3 mths prior to the study; 19. Patients using the following drugs within 5-times the half-life prior to start with the baseline pain intensity assessment (Visit 1 or 2) before the randomization visit: antidepressants, anticonvulsants or mexiletine for the treatment of pain, opioids or morphinomimetics, fatty acid supplements, primrose oil, myoinositol, chromium picolinate, alpha-lipoic acid, benfotiamin that are known to be used in neuropathic pain, acetyl salicylic acid more than 325 mg/day and not indicated for myocardial infarction or transient ischemic attack prophylaxis, NSAIDs for the treatment of pain, benzodiazepines other than indicated at low doses for sleep disorders, muscle relaxants, any drugs containing paracetamol/acetaminophen, OCT2 inhibitors such as cimetidine, ofloxacin, levofloxacin, phenazopyridine, piliscainide, quinidine, quinine, ranitidine 20. Electroconvulsive therapy within 30 days of baseline evaluation (Visit 3); 21. Regular use of capsaicin in the 6 mths before the study; 22. Prior neurolytic treatment or intrathecal pumps for treatment of pain; 23. Physiotherapy if not stable 1 mth before and during the study; 24. Patients with short life expectancy; 25. Patients with a history of HIV infection and/or with active hepatitis B or C; 26. Use of any investigational drug product within 3 mths or within 5 half-lives prior to the study whichever is longer; 27. Patients who are illiterate or are judged by the investigator to be unable or unlikely to understand the nature, scope and possible consequences of the study; 28. Patients under any administrative or legal supervision. Related to SAR407899A 29. Patients with symptomatic hypotension whatever the decrease in blood pressure, or asymptomatic postural hypotension defined by a decrease in systolic blood pressure ≥ 20 mmHg within three minutes when changing from the supine to the standing position; 30. Patients with AST and/or ALT > 3 x upper laboratory norms; 31. Pregnant or breastfeeding women; 32. Women of child-bearing potential, unless they meet one of the following criteria: Committed to use a double barrier method of contraception during the entire study, including the screening period, including [intrauterine device or hormonal contraception] plus [condom or diaphragm or spermicidal]. Women using oral contraception must also have done so for 3 mths prior to the randomization (Visit 3), To be considered not of child-bearing potential, women must be post-menopausal for at least 2 years or surgically sterile. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Change in the average daily pain intensity as measured on the 11 point NRS defined as the mean of the last 7 days of the treatment period compared to baseline. |
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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 | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
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) | 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 | 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 | 8 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 24 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
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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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 | 9 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 9 |