Ranolazine for Diabetic Peripheral Neuropathic Pain (DPNP)

Diabetic Peripheral Neuropathic Pain Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02156336
• Other study ID #: HIPG-CLIN-2014-01
• Status: Terminated
• Phase: Phase 4
• First received: May 28, 2014
• Last updated: February 9, 2017
• Start date: May 2014
• Est. completion date: February 8, 2017

Study information

• Verified date: February 2017
• Source: Horizons International Peripheral Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 4
• Est. completion date: February 8, 2017
• Est. primary completion date: February 8, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Diabetic Neuropathies
• Diabetic Peripheral Neuropathic Pain
• Neuralgia

Intervention

Drug:
• Ranolazine
Oral administration, BID; for a maximum of 51 days.
• Placebo
Oral administration, BID; for a maximum of 51 days.

Locations

Country	Name	City	State
United States	Cardiology Associates	Fairhope	Alabama
United States	Cardiovascular Institute of the South	Houma	Louisiana
United States	Cardiovascular Institute of the South	Lafayette	Louisiana

Sponsors (2)

Lead Sponsor	Collaborator
Horizons International Peripheral Group	Gilead Sciences

Country where clinical trial is conducted

United States, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Change in Quality of Life Assessment as measured by SF-36 v2		Randomization (Day 0) and Day 42
Secondary	Change in pain assessment measured by the Visual Analog Scale		Randomization (Day 0), Day 14, Day 28, Day 42, and Day 56
Secondary	Change in pain assessment measured by Short-Form McGill Pain Questionnaire		Randomization (Day 0) and Day 42
Secondary	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
Secondary	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
Secondary	Occurrence of Adverse Events after randomization	The rates and severity of Adverse Events (AEs) from Randomization (Day 0) through Termination (Day 56)	56 Days
Secondary	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