A Clinical Trial to Study the Effects of GRC 17536 in Patients With Painful Diabetic Neuropathy (Painful Extremities Due to Peripheral Nerve Damage in Diabetic Patients)

A Phase II, 4 Week Randomized, Double-Blind, Parallel Group, Placebo Controlled Proof of Concept Study to Evaluate Efficacy, Safety and Tolerability of GRC 17536 in Patients With Painful Diabetic Neuropathy

Diabetic peripheral neuropathy (DPN) represents a diffuse symmetric and length-dependent injury to peripheral nerves that has major implications on quality of life (QOL), morbidity, and costs from a public health perspective. Painful diabetic neuropathy affects 16% of patients with diabetes. Pharmacological agents used in the management of painful DPN mainly include tricyclic antidepressants, selective serotonin and norepinephrine reuptake inhibitors, opioids, and anti epileptic drugs. However, only two drugs (duloxetine and pregabalin) have been formally approved by the EMEA and the US FDA for the treatment of painful DPN. Generally, the available treatment options do not give total relief, are not effective in all patients, and only about one-third of patients may achieve more than 50% pain relief. Hence newer therapies are required for the treatment of DPN.

This is randomized, double-blind, placebo-controlled, parallel group study. The study will include patients with type 1 or type 2 diabetes mellitus with history of pain attributed to DPN for least 6 months and no greater than 5 years.

Patients will be recruited after providing written informed consent.

Study Overview

• Status: Withdrawn
• Conditions: Painful Diabetic Neuropathy
• Intervention / Treatment: Drug: GRC 17536 (Medium Dose); Drug: GRC 17536 (Low Dose); Drug: Placebo

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

Study Locations

• Germany
  • Mainz, Germany
    • Site 2
• United Kingdom
  • Manchester, United Kingdom
    • Site 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 with painful peripheral neuropathy for at least 6 months
4. A baseline 24-hour average daily pain intensity score ≥5
5. Women must be of non child-bearing potential, defined as post menopausal or surgically sterile.

Exclusion Criteria:

1. Other chronic pain conditions not associated with DPN, that may confound the assessment of neuropathic pain
2. Other causes of neuropathy or lower extremity pain
3. Complex regional pain syndrome or trigeminal neuralgia
4. Lower extremity amputations other than toes
5. Participation in another study with an investigational compound within the previous 90 days prior to study medication administration, or concurrent participation in another clinical study
6. Major depression.
7. Presence or history of cancer within the past 5 years with the exception of adequately treated localized basal cell skin cancer or in situ uterine cervical cancer.
8. Patients with clinically significant or uncontrolled hepatic, gastrointestinal, cardiovascular, respiratory, neurological (other than neuropathy), psychiatric, hematological, renal, or dermatological disease, or any other medical condition that according to Investigator's medical judgment: Could interfere with the accurate assessment of safety or efficacy, or, Could potentially affect a patient's safety or study outcome

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Treatment Arm 1	Drug: GRC 17536 (Medium Dose); 1 BD for 28 days
Active Comparator: Traetment Arm 2	Drug: GRC 17536 (Low Dose); 1 BD for 28 Days
Placebo Comparator: Treatment Arm 3	Drug: Placebo; Matching Placebo for 28 Days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Mean 24-hour average pain intensity (API) score	4 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Mean night-time API Score	4 weeks
Patient Global Impression of Change	4 weeks
Clinician Global Impression of Change	4 weeks
Adverse events (AE)	4 weeks
Pharmacokinetics: Cmax, Tmax, AUC 0-tau, AUC0-24	4 weeks

Collaborators and Investigators

• Sponsor: Glenmark Pharmaceuticals Ltd. India
• Collaborators: Glenmark Pharmaceuticals S.A.
• Investigators: Study Director: Dr. Kavita Muchandi, MD, Glenmark Pharmaceuticals Ltd

Study record dates

Study Registration Dates

• First Submitted: March 15, 2012
• First Submitted That Met QC Criteria: March 15, 2012
• First Posted (Estimate): March 16, 2012

Study Record Updates

• Last Update Posted (Estimate): November 12, 2012
• Last Update Submitted That Met QC Criteria: November 9, 2012
• Last Verified: November 1, 2012

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Neurologic Manifestations; Endocrine System Diseases; Diabetes Complications; Diabetes Mellitus; Neuromuscular Diseases; Peripheral Nervous System Diseases; Pain; Diabetic Neuropathies
• Other Study ID Numbers: GRC 17536-201; 2011-005879-16 (EudraCT Number)