Ranolazine for Diabetic Peripheral Neuropathic Pain (DPNP)

A Double-Blind, Placebo-Controlled, Randomized, Parallel Assignment, U.S. Study of Ranolazine for the Treatment of Patients With Diabetic Peripheral Neuropathic Pain (DPNP)

The purpose of this trial is to determine if patients suffering from diabetic peripheral neuropathic pain treated with ranolazine will have a greater reduction in pain compared to placebo.

Hypothesis: From the prior clinical observations, and analgesic efficacy in the preclinical animal model of neuropathic pain, the investigators hypothesize that subjects randomized to ranolazine will show a greater reduction in diabetic neuropathic pain compared to placebo.

Study Overview

• Status: Terminated
• Conditions: Diabetic Peripheral Neuropathic Pain
• Intervention / Treatment: Drug: Placebo; Drug: Ranolazine

• Study Type: Interventional
• Enrollment (Actual): 4
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Fairhope, Alabama, United States, 36532
      • Cardiology Associates
  • Louisiana
    • Houma, Louisiana, United States, 70361
      • Cardiovascular Institute of the South
    • Lafayette, Louisiana, United States, 70503
      • Cardiovascular Institute of the South

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. A minimum of 18 years of age;
2. Provided signed Informed Consent Form and Health Insurance Portability and Accountability Act (HIPAA) authorization for this study approved by the Institutional Review Board;
3. Patients must have diabetic peripheral neuropathic pain rated at an average level of six (6) or above as documented in daily diary prior to baseline visit and noted at Baseline Visit;
4. Diabetic on a stable insulin regimen or oral medication regimen as determined by the investigator [It is recommended Hba1c < 9.5%, making a note that lab normal values may vary among sites.];

5. Clinical Exam Results:

   1. 5.07 Semmes-Weinstein Monofilament Test Subject does not sense monofilament or evokes an abnormal response in a minimum of two (2) out of five (5) test locations on the plantar surface of the foot.
   2. Pin Prick Test Subject experiences allodynia, hyperalgesia, or sensory loss in two (2) out of five (5) test locations in the plantar surface - four (4) and dorsum - one (1) of the foot.
6. Willing and able to comply with the requirements of the protocol and follow directions from the clinic and research staff;

7. For female patients only:

   • Be post-menopausal (no menses for at least 2 years) or sterilized,

   • If subject of childbearing potential, not breastfeeding, has a negative pregnancy test at Baseline (pre-randomization, Day 0), has no intention of becoming pregnant during the course of the study, and is using one or more of the following contraceptive measures:

     1. Stable regimen of hormonal contraception
     2. Intra-uterine device
     3. Condoms with spermicide
     4. Diaphragm with spermicide

Exclusion Criteria:

1. History of allergy or intolerance to ranolazine;
2. Any condition or concomitant medication that would preclude the safe use of ranolazine as outlined in the prescribing information sheet;
3. In the judgment of the investigator, any clinically-significant ongoing medical condition that might jeopardize the patient's safety or interfere with the absorption, distribution, metabolism or excretion of the study drug;
4. In the judgment of the investigator, clinically-significant abnormal physical findings during screening (excluding the patient's peripheral neuropathy condition);
5. Use participation in another experimental or investigational drug or device trial;
6. Pregnant or breast feeding;
7. Cirrhosis of the liver;
8. Psychological or addictive disorders (not limited to, but including for example, drug and/or alcohol dependency) that may preclude patient consent or compliance, or that may confound study interpretation;
9. Taking a moderate or strong CYP3A inhibitor (e.g. diltiazem, verapamil, ketoconazole, itraconazole, clarithromycin, erythromycin, nefazodone, nelfinavir, ritonavir, indinavir, and saquinavir);
10. Taking inducers of Cytochrome P450, family 3, subfamily A (CYP3A) (e.g. rifampin, rifabutin, rifapentine, phenobarbital, phenytoin, carbamazepine, and St. John's wort);
11. Renal impairment as defined by a calculated serum creatinine clearance of < 30ml/min;
12. Lower back disorders where symptoms present similarly to DPNP;
13. Family history of long QT syndrome;
14. Congenital long QT syndrome;
15. Subjects taking tricyclic antidepressants;
16. Subjects taking anti-psychotic drugs;
17. Patient is taking > 850mg metformin BID;
18. Any subjects currently taking pregabalin;
19. Any subjects currently taking gabapentin;
20. Any subject currently taking Metanx®;
21. Any subjects currently taking continuous long-term narcotics;
22. Grapefruit and grapefruit containing products;
23. Use of P-gp inhibitors - cyclosporine.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: PLACEBO; 500 mg PLACEBO PO 2 times a day for 1 week (Week 1); 1000 mg PLACEBO PO 2 times a day for 5 weeks (Weeks 2,3,4,5,6)	Drug: Placebo; Oral administration, BID; for a maximum of 51 days.; Other Names: Sugar Pill
Active Comparator: RANOLAZINE; 500 mg RANOLAZINE PO 2 times a day for 1 week (Week 1); 1000 mg RANOLAZINE PO 2 times a day for 5 weeks (Weeks 2,3,4,5,6)	Drug: Ranolazine; Oral administration, BID; for a maximum of 51 days.; Other Names: Ranexa

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Fifty percent or greater reduction in the mean Numeric Rating Scale (11-point NRS 0-10) recorded in the subjects' diaries from ranolazine compared to placebo.	6 weeks (42 Days)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Quality of Life Assessment as measured by SF-36 v2		Randomization (Day 0) and Day 42
Change in pain assessment measured by the Visual Analog Scale		Randomization (Day 0), Day 14, Day 28, Day 42, and Day 56
Change in pain assessment measured by Short-Form McGill Pain Questionnaire		Randomization (Day 0) and Day 42
Change in pain of patients with arterial ischemia measured by Short-Form McGill Pain Questionnaire	Pain reduction of ranolazine versus placebo in subjects with diabetic peripheral neuropathic pain (DPNP) and arterial ischemia compared to those with DPNP without arterial ischemia.	Randomization (Day 0), Day 14, Day 28, Day 42, and Day 56
Additional pain medication	Additional pain medication after the baseline visit as needed for pain reduction in addition to the study drug.	Randomization (Day 0), Day 14, Day 28, Day 42, and Day 56
Occurrence of Adverse Events after randomization	The rates and severity of Adverse Events (AEs) from Randomization (Day 0) through Termination (Day 56)	56 Days
Occurrence of Serious Adverse Events after randomization	A serious adverse event (SAE), also may be called a serious adverse drug reaction, is any untoward medical occurrence that at any dose: results in death,; is life-threatening,; requires inpatient hospitalization or prolongation of existing hospitalization,; results in persistent or significant disability/incapacity, or; is a congenital anomaly/birth defect.	56 Days

Collaborators and Investigators

• Sponsor: Horizons International Peripheral Group
• Collaborators: Gilead Sciences
• Investigators: Principal Investigator: Craig M Walker, MD FACC, Cardiovascular Institute of the South

Publications and helpful links

General Publications

• Gould HJ 3rd, Garrett C, Donahue RR, Paul D, Diamond I, Taylor BK. Ranolazine attenuates behavioral signs of neuropathic pain. Behav Pharmacol. 2009 Dec;20(8):755-8. doi: 10.1097/FBP.0b013e3283323c90.

Study record dates

Study Major Dates

• Study Start: May 1, 2014
• Primary Completion (Actual): February 8, 2017
• Study Completion (Actual): February 8, 2017

Study Registration Dates

• First Submitted: May 28, 2014
• First Submitted That Met QC Criteria: June 4, 2014
• First Posted (Estimate): June 5, 2014

Study Record Updates

• Last Update Posted (Actual): February 10, 2017
• Last Update Submitted That Met QC Criteria: February 9, 2017
• Last Verified: February 1, 2017

More Information

Terms related to this study

• Keywords: Ranolazine; Neurology; Diabetic Peripheral Neuropathic Pain; Ranexa
• Additional Relevant MeSH Terms: Nervous System Diseases; Pain; Neurologic Manifestations; Endocrine System Diseases; Diabetes Complications; Diabetes Mellitus; Neuromuscular Diseases; Peripheral Nervous System Diseases; Neuralgia; Diabetic Neuropathies; Molecular Mechanisms of Pharmacological Action; Membrane Transport Modulators; Sodium Channel Blockers; Ranolazine
• Other Study ID Numbers: HIPG-CLIN-2014-01