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-DE
• Lead Sponsor: Glenmark Pharmaceuticals SA

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2012-01-27
• 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.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: <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.
Diabetic regimens may be changed after randomization to maintain glycaemic control. Patients will receive guideline-based diabetes control that is individually adapted to their comorbidity and risk profile.
Patients with HbA1c of 8 to 11% are eligible if attempts to improve diabetic control with optimal treatment with authorized drugs have failed.
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) 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.
12) It is required that all male patients with partners of child-bear

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

Study & Design

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