Ranolazine for Diabetic Peripheral Neuropathic Pain (DPNP)
Study Details
Study Description
Brief Summary
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 4 |
Study Design
Arms and Interventions
| 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:
|
| 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:
|
Outcome Measures
Primary Outcome Measures
- 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
- 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 [Randomization (Day 0), Day 14, Day 28, Day 42, and Day 56]
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.
- Additional pain medication [Randomization (Day 0), Day 14, Day 28, Day 42, and Day 56]
Additional pain medication after the baseline visit as needed for pain reduction in addition to the study drug.
- Occurrence of Adverse Events after randomization [56 Days]
The rates and severity of Adverse Events (AEs) from Randomization (Day 0) through Termination (Day 56)
- Occurrence of Serious Adverse Events after randomization [56 Days]
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.
Eligibility Criteria
Criteria
Inclusion Criteria:
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A minimum of 18 years of age;
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Provided signed Informed Consent Form and Health Insurance Portability and Accountability Act (HIPAA) authorization for this study approved by the Institutional Review Board;
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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;
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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.];
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Clinical Exam Results:
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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.
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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.
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Willing and able to comply with the requirements of the protocol and follow directions from the clinic and research staff;
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For female patients only:
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Be post-menopausal (no menses for at least 2 years) or sterilized,
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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:
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Stable regimen of hormonal contraception
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Intra-uterine device
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Condoms with spermicide
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Diaphragm with spermicide
Exclusion Criteria:
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History of allergy or intolerance to ranolazine;
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Any condition or concomitant medication that would preclude the safe use of ranolazine as outlined in the prescribing information sheet;
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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;
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In the judgment of the investigator, clinically-significant abnormal physical findings during screening (excluding the patient's peripheral neuropathy condition);
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Use participation in another experimental or investigational drug or device trial;
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Pregnant or breast feeding;
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Cirrhosis of the liver;
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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;
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Taking a moderate or strong CYP3A inhibitor (e.g. diltiazem, verapamil, ketoconazole, itraconazole, clarithromycin, erythromycin, nefazodone, nelfinavir, ritonavir, indinavir, and saquinavir);
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Taking inducers of Cytochrome P450, family 3, subfamily A (CYP3A) (e.g. rifampin, rifabutin, rifapentine, phenobarbital, phenytoin, carbamazepine, and St. John's wort);
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Renal impairment as defined by a calculated serum creatinine clearance of < 30ml/min;
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Lower back disorders where symptoms present similarly to DPNP;
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Family history of long QT syndrome;
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Congenital long QT syndrome;
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Subjects taking tricyclic antidepressants;
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Subjects taking anti-psychotic drugs;
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Patient is taking > 850mg metformin BID;
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Any subjects currently taking pregabalin;
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Any subjects currently taking gabapentin;
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Any subject currently taking Metanx®;
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Any subjects currently taking continuous long-term narcotics;
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Grapefruit and grapefruit containing products;
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Use of P-gp inhibitors - cyclosporine.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Cardiology Associates | Fairhope | Alabama | United States | 36532 |
| 2 | Cardiovascular Institute of the South | Houma | Louisiana | United States | 70361 |
| 3 | Cardiovascular Institute of the South | Lafayette | Louisiana | United States | 70503 |
Sponsors and Collaborators
- Horizons International Peripheral Group
- Gilead Sciences
Investigators
- Principal Investigator: Craig M Walker, MD FACC, Cardiovascular Institute of the South
Study Documents (Full-Text)
None provided.More Information
Publications
- HIPG-CLIN-2014-01