A 4 week study to evaluate the effectiveness and safety of GRC 17536 a new medication in patients with diabetes who have nerve involvement

• Conditions: Pain associated with diabetic peripheral neuropathy (DPN).; MedDRA version: 14.1Level: LLTClassification code 10012683Term: Diabetic peripheral neuropathySystem Organ Class: 10029205 - Nervous system disorders; Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

• Registration Number: EUCTR2011-005879-16-GB
• Lead Sponsor: Glenmark Pharmaceuticals SA

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2012-03-28
• Last Update Posted: 28 August 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 55

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.
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: <25% change of their current insulin dose to maintain glycaemic control
b) Oral antidiabetic agents: <50% change of their current oral dose to maintain glycaemic control.
c) Addition of 1 oral hypoglycaemic agent at its therapeutic dose to the existing treatment regimen.
10) Patients detected to have mechanical hyperalgesia and/or cold allodynia on the basis of appropriate methodology: The study will intend to randomize at least 5 patients with either mechanical hyperalgesia and/or cold allodynia into each of the 3 treatment arms (90 mg, 250/30 mg and placebo).
11) HbA1c level <11
12) Women must be of non child-bearing potential, defined as post menopausal or surgically sterile.
• Menopause is defined as:
• 12 months of spontaneous amenorrhea or
• 6 months of spontaneous amenorrhea with a serum follicular stimulating hormone (FSH) level >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.
13) It is required that all male patients with partners of child-bearing capacity use the following methods of contraception from the first dose of study medication and until 90 days after the last dose as shown below:
All sexually active males must use a condom in addition to one of the following conditions:
1) Male patients must have had a vasectomy for more than 6 months
2) Female partner who meets one of the following conditions:
• has had a bilateral tubal ligation, hysterectomy, or bilateral oophorectomy;
• is post-menopausal;
• uses one of the following forms of contraception:
1. consistent use of oral, injected or implanted hormonal methods of contraception
2. Placement of intra-uterine device (IUD) or intra-uterine system (IUS)
3. Barrier methods only wh

Exclusion Criteria

1) Patients with a 24-hour daily average pain intensity of = 9 on the 11-point NRS at visit 1 or visit 3
2) Other chronic pain conditions not associated with DPN that may confound the assessment of neuropathic pain. However, the patient will not be excluded if:
a)The pain condition is located 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) 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) Past medical history or known current medical condition of diffuse peripheral neuropathy caused by alcoholism, malignancy, human immunodeficiency virus (HIV), syphilis, drug abuse, peripheral ischaemia, Vitamin B 12 deficiency, 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 drugs within 7 days prior to start with the baseline pain intensity assessment ( i.e, 7 days prior to visit 2)
a) Antidepressants, anticonvulsants or mexiletine
b) Opioids or morphinomimetics
c) Fatty acid supplements, primrose oil, myoinositol, chromium picolinate that are known to be used in neuropathic pain
d) Acetyl salicylic acid (ASA) except up to 325 mg/d post myocardial infarction or prevention, 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]) for the relief of pain of DPN for the required 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 last 03 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) 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 a positive Hepatitis B surface antigen (HBsAg) or Hepatitis C Core Antigen Antibody (Hep C antibody).
c) Serum creatinine >150 µmol/L
d) Corrected QT (QTc) interval using Bazett’s correction >430 msec in males >450msec in females based on single or average QTc value of triplicate electrocardiograms (ECGs) obtained over a brief recording period.
e) Uncontrolled hypertension at screening (sitting systolic blood pressure [SBP] >160 mmHg and/or sitting diastolic blood pressure [DBP] >90 mmHg.
f) Current diagnosis of active epilepsy or any active seizure disorder requiring chronic therapy with antiepileptic drug(s).
g) Patients with clinically si

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified