Pain associated with diabetic peripheral neuropathy (DPN). MedDRA version: 20.0 Level: LLT Classification code 10012683 Term: Diabetic peripheral neuropathy System Organ Class: 100000004852
Conditions
Interventions
Product Name: GRC 17536 potassium granules
Product Code: GRC 17536 potassium
Pharmaceutical Form: Granules for oral suspension
Current Sponsor code: GRC
Sponsors
Glenmark Pharmaceuticals SA
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1) Patients willing to provide voluntary written informed consent 2) Male and female (post menopausal/surgically sterile only) patients =18 yrs and = 75 yrs 3) Patients with diabetes mellitus (type 1 or 2) with distal symmetric chronic sensorimotor painful peripheral neuropathy 4) A history of pain for at least 6 months and no greater than 5 years attributed to DPN (Note this requirement refers to duration of pain, not the duration of DPN). 5) DN4 (Douleur Neuropathique en 4 questions) score of =4 6) A baseline 24-hour average daily pain intensity score =5 and 40 mIU/L Surgically sterile women: defined as females who hav
Exclusion criteria
Exclusion criteria: Patients meeting any of the following criteria must not be enrolled in the study: 1) 24-hour daily average pain intensity of = 9 on the 11-point NRS at visits 1 or 3 2) Other chronic pain conditions not associated with DPN that may confound the assessment of neuropathic pain. Patients will not be excluded if: a) pain condition is located at a different region of the body (other than lower limbs), and b) pain intensity of this condition is not greater than the pain intensity of DPN, and c) The patient can assess pain due to DPN independently of their other pain condition. 3) Other causes of neuropathy or lower extremity pain which may include, but not be limited to: a) Lower extremity pain of any severity caused by: osteoarthritis of the ankle or foot, gout, bursitis, or fasciitis. b) diffuse peripheral neuropathy caused by alcoholism, malignancy, human immunodeficiency virus (HIV), syphilis, drug abuse, peripheral ischaemia, Vitamin B 12 deficiency, abnormal folate, hypothyroidism, liver disease, chemotherapy or radiation therapy. c) Focal neuropathy in the lower extremities including nerve entrapment or local trauma. d) Acute or chronic inflammatory polyradiculopathy. e) Multiple sclerosis or other conditions associated with central neuropathic pain. f) Pain associated with distal limb ischaemia including intermittent claudication. 4) Complex regional pain syndrome or trigeminal neuralgia 5) Use of the following within 7 days prior to start with the baseline pain intensity assessment a) Antidepressants, anticonvulsants or mexiletine (exceptions: fluvoxamine, norfluoxetine, nefazodone, carbamazepine, barbiturates, phenytoin and oxcarbazepine-patients on these medications at screening will be excluded) b) Opioids or morphinomimetics c) Fatty acid supplements, primrose oil, myoinositol, chromium picolinate, alpha-lipoic acid, benfotiamine, actovegin that are known to be used in neuropathic pain d) Acetyl salicylic acid except up to 325 mg/day for myocardial infarction or transient ischaemic attack prophylaxis e) Benzodiazepines other than indicated at low doses for sleep disorders f) Lidocaine patch g) Non-drug therapies or procedures (i.e. nerve blocks, trans cutaneous electrical nerve stimulation [TENS]). 6) Use of herbal medication/supplements, St Johns wort and grape-fruit juice (more than 0.9 L/day) within 3 weeks prior to visit 2 7) Capsaicin use within 3 months of screening 8) Diabetic foot ulcer of = 3 months duration 9) Lower extremity amputation other than toes 10) Has any of the following laboratory abnormalities, medical conditions or disorders: a) Alanine aminotransferase (ALT) > 1.5x upper limit of normal (ULN) or direct bilirubin > 1.5x ULN. b) Chronic hepatitis B or C with
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the efficacy of GRC 17536 in the treatment of pain associated with diabetic peripheral neuropathy (DPN).;Primary end point(s): The primary endpoint is the change from baseline to end of treatment (i.e., baseline to end of week 4) in the mean 24-hour average pain intensity (API) score based on an 11 point pain intensity numeric rating scale (NRS); Timepoint(s) of evaluation of this end point: Baseline to end of week 4 ; Secondary Objective: 1. To evaluate the safety and tolerability of GRC 17536 administered BID in patients with painful DPN 2. To investigate the effect of GRC 17536 on time to sustained improvement in pain, night-time pain, neuropathic pain symptoms (NPSI), and sleep interference in patients with painful DPN. 3. To evaluate number of patients who are responders on the Patient Global Impression of Change (PGIC) questionnaire, Clinician Global Impression of Change (CGIC) questionnaire; and number of patients who achieve various levels of percent reduction in pain 4. To investigate the pharmacokinetics (PK) of GRC 17536 in patients with DPN 5. To investigate the effect of GRC 17536 on the use of rescue medication in patients with painful DPN 6. To investigate the effect of GRC 17536 in patients with painful DPN who have mechanical hyperalgesia and /or cold allodynia | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1) Secondary endpoints 1. Change from baseline at the end of week 1, 2, 3, 4 and 6 in: 2. Mean night-time API Score (patient diary): night-time is defined as the time between going to bed at night and rising in the morning 3. Mean night-time worst pain intensity Score (patient diary): worst pain is defined as the patient’s assessment of their worst pain intensity for the time period. 4. Mean sleep interference Score (patient diary): An 11-point scale that asks patients to select the score that best describes how much the pain interfered with sleep during the past 24 hours. A score 0=Did not interfere with sleep, 10=unable to sleep due to pain. 5. Mean daily dose of rescue medication (patient diary) 6. Number of patients who are responders on the PGIC questionnaire (visits) 7. Number of patients who are responders on the CGIC questionnaire (visits) 8. Number of patients achieving various levels of percent reduction from baseline in the mean 24-hour API score (derived from NRS score) 9. Time to onset of sustained improvement in the 24-hour daily average pain intensity Score: Sustained improvement is defined as a reduction of = 2 points from baseline for = 2 consecutive days on the 24-hour daily API scores on NRS. 10. NPSI (visits) 11. Quantitative sensory testing (QST) assessments 12. Change from baseline in the 24 hour daily API on NRS at the end of week 1, 2, 3 and 6 13. Other: In addition, at all visits from visit 2 onwards until visit 8, the investigator will ask the patient “Compared to the previous visit, has your pain characteristic changed?” If the response to this question is yes, the patient must be asked to describe the pain in his/her words. This must be documented in the patient source files and case record form (C | — |
Countries
Czech Republic, Germany, India, United Kingdom
Contacts
Public ContactKavita Muchandi
Glenmark Pharmaceuticals SA
Outcome results
None listed