A 4 week study to evaluate the effectiveness and safety of GRC 17536 a new medication in patients with diabetes who have peripheral 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: EUCTR2012-002320-33-DE
• Lead Sponsor: Glenmark Pharmaceuticals SA

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2012-07-02
• Last Update Posted: 16 November 2015

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 138

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 < 9 as measured on an 11 point pain intensity NRS. The baseline score is the calculated as mean of the 24-hour daily average pain scores during the 7 days prior to randomisation. The patient must record at least 4 assessments of the 24-hour daily average pain intensity score during the 7-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 entire 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, AEs, 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 randomisation (for subjects with HbA1c < 8%) as defined by:
a) Insulin: <25% change of their mean 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 up to 1 oral hypoglycaemic agent at its therapeutic dose to the existing treatment regimen.
Patients with HbA1c of 8 to 11% are eligible if attempts to improve diabetic control with optimal treatment with authorized drugs have failed.
Diabetic regimens may be changed after randomisation to maintain glycaemic control. Patients will receive guideline-based diabetes control that is individually adapted to their comorbidity and risk profile.
10) Patients detected to have mechanical hyperalgesia and/or cold allodynia on the basis of appropriate methodology: The study will intend to randomise at least 38 patients with either mechanical hyperalgesia and/or cold allodynia out of the total 138 planned patients.
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 with a serum follicular stimulating hormone (FSH) level >40 mIU/L
Surgically sterile women: defined as 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 use the following methods of contraception from the first dose of study medication and until 90 days after the last dose as shown below:

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 a positive Hepatitis B surface antigen or
Hepatitis C Core Antigen 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 SBP >160 mmHg
and/or sitting 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 significant or uncontrolled hepatic, gastrointestinal, cardiovascular, respiratory, neurological (other than neuropathy), psychiatric, hemat

Study & Design

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