Pain associated with diabetic peripheral neuropathy (DPN). MedDRA version: 14.1 Level: LLT Classification code 10012683 Term: Diabetic peripheral neuropathy System Organ Class: 10029205 - Nervous system disorders
Conditions
Interventions
Product Name: GRC 17536 potassium granules
Product Code: GRC 17536 potassium
Pharmaceutical Form: Granules for oral suspension
Current Sponsor code: GRC 17536 potassium
Concentration unit: mg milligra
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 (women of non child-bearing potential) 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 as measured on a 11 point pain intensity NRS. The baseline score is the calculated mean of the 24-hour daily average pain scores during the 7 days prior to randomization. The patient must record at least 4 assessments of the 24-hour daily average pain intensity score during the seven-day placebo run-in period in the patient diary. 7) Pain uncontrolled with up to 2 medications for the treatment of pain associated with DPN. The patient’s medical history may indicate that the pain was not controlled with: a) 1 medication for painful DPN or b) 2 medications for painful DPN taken over different time-periods in the past or c) 2 medications for painful DPN taken over the same time-periods in the past (ie combination therapy using 2 drugs) 8) Patients willing to withdraw their neuropathy medications for the whole duration of study starting from washout period till end of study visit.Discontinuation of ongoing diabetic neuropathy pain medications during the study (from wash-out period to visit 8) must be medically justifiable and appropriate (eg, inadequate pain control, adverse events, contra-indication etc). Patients who are stable on the ongoing pain medications and have no medical justification to withdraw these medications will not be included in the study. 9) Stable glycaemic control for three months prior to randomization (diabetic regimens may be changed after randomization to maintain glycaemic control) as defined by: a) Insulin: 40 mIU/L • Surgically sterile: Females who have a documented hysterectomy and/or bilateral oophorectomy at least 6 weeks before screening. Tubal ligation does not constitute non-child bearing potential. 12) It is required that all male patients with partners of child-bear
Exclusion criteria
Exclusion criteria: 1)Patients with 24-hour daily average pain intensity = 9 on 11-point NRS at visit 1 or 3 2)Other chronic pain conditions. However, the patient will not be excluded if: a)The pain is at a different region of the body (other than lower limbs), and b)The pain intensity of this condition is not greater than the pain intensity of DPN, and c)They can assess pain due to DPN independently of their other pain condition. 3)Other causes of neuropathy or lower extremity pain including but not limited to: a)Osteoarthritis of the ankle or foot, gout, bursitis, or fasciitis. b)Medical history or known current medical condition of diffuse peripheral neuropathy caused by alcoholism, malignancy, HIV, syphilis, drug abuse, peripheral ischaemia, Vitamin B 12 deficiency, hypothyroidism, liver disease, chemotherapy or radiation therapy. c)Focal neuropathy in 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 of the baseline pain intensity assessment a)Antidepressants, anticonvulsants or mexiletine b)Opioids or morphinomimetics c)Fatty acid supplements, primrose oil, myoinositol, chromium picolinate d)Acetyl salicylic acid except up to 325 mg/d post myocardial infarction or prevention, transient ischaemic attack prophylaxis e)Benzodiazepines other than at low doses for sleep disorders f)Lidocaine patch g)Non-drug therapies or procedures for the relief of pain for the run in period and throughout the duration of the study. h)Herbal medication/supplements, St Johns wort and grape fruit juice (more than 1 quart/day) 6)Capsaicin use within 3 months of screening 7)Diabetic foot ulcer of = 3 months duration. Diabetic foot ulcer of > 3months can be included in the study only if the ulcer has been stable for a period of at least 3 months prior to screening. 8)Lower extremity amputations other than toes 9)Any of the following lab abnormalities, medical conditions or disorders: a)ALT > 1.5x upper limit of normal (ULN) or direct bilirubin > 1.5x ULN. b)Chronic hepatitis B or C with a positive Hepatitis B surface antigen or Hepatitis C Core Antigen Antibody c)Serum creatinine >150 µmol/L d)Corrected QT (QTc) interval >430 msec in males >450msec in females e)Uncontrolled hypertension at screening (sitting systolic blood pressure >160 mmHg and/or sitting diastolic blood pressure >90 mmHg. f)Current diagnosis of active epilepsy or any active seizure disorderrequiring chronic antiepileptic therapy g)Clinically significant or uncontrolled hepatic, GI, cardiovascular, respiratory, neurological (other than neuropathy), psychiatric, hematological, renal, or dermatological disease, or other medical condition that according to Investigator's medical judgment: • Could interfere with the assessment of safety or efficacy, or, •Could potentially affect a patient's safety or study outcome. 10)Participation in another study within 90 days, or concurrent participation in another clinical study 11)Major depression. 12)Presence or history of cancer within 5 years with the exception of adequately treated localized basal cell skin cancer or in situ uterine cervical cancer. 13)Past medical history or known curren
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 co-primary efficacy variables (endpoints) are change from baseline to end of each treatment (i.e., baseline to end of week 2; from end of week 2 to end of week 4; and baseline to end of week 4) in the mean 24-hour API score based on a 11-point pain intensity NRS;Timepoint(s) of evaluation of this end point: 1 Baseline to end of week 2 2 End of week 2 to end of week 4 3 Baseline to end of week 4 ;Secondary Objective: 1. To evaluate the safety and tolerability of GRC 17536 administered once daily (OD) or twice daily (BID) in patients with painful DPN 2. To investigate the effect of GRC 17536 on time to sustained improvement in pain, night time pain, intensity of pain on neuropathic pain symptoms inventory (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 effect of GRC 17536 on the use of rescue medication in patients with painful DPN 6. To investigate 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) Efficacy variables (endpoints): a) Change from baseline at the end of week 1, 2, 3, 4 and 6 in: • 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 • 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. • Mean sleep interference Score (patient diary): A 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. • Mean daily dose of rescue medication (patient diary) • Number of patients who are responders on the Patient Global Impression of Change (PGIC) Questionnaire (visits) • Number of patients who are responders on the Clinician Global Impression of Change (CGIC) Questionnaire (visits) • Number of patients achieving various levels of percent reduction from baseline in the mean API score (derived from NRS score) • Time to onset of sustained improvement in the 24-hour daily average pain intensity Score. • Pain intensity as assessed by the neuropathic pain symptom inventory (NPSI) • QST assessments b) Change from baseline in the 24 hour daily API on NRS at the end of week 1, 3 and 6 • 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. 2) Safety variables (endpoints): a) Physical examination – body weight b) Vital signs (including BP, HR, temperature) c) ECG d) Clinical laboratory safety analysis (haematology, coagulation, biochemistry and urinalysis) e) Adverse events 3) Pharmacokinetic Va | — |
Countries
Germany, United Kingdom
Contacts
Public ContactKavita Muchandi
Glenmark Pharmaceuticals SA
Outcome results
None listed