Study of Ranexa in Patients With Coronary Artery Disease and Painful Polyneuropathy

• Sponsor: Gilead Sciences (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT00832572
• Collaborator: (none)
• Enrollment: 5
• Location: 1
• Arms: 2
• Duration (Months): 5
• Patients Per Site Per Month: 1

Study Details

Study Description

Brief Summary

This study was to determine whether ranolazine was effective in the treatment of neuropathic pain in patients with coronary artery disease.

Eligibility required neurological examination by the study doctor and assessment of the patient's pain. Eligible participants were randomized to receive blinded study medication for a total of 12 weeks.

Condition or Disease	Intervention/Treatment	Phase
Coronary Artery Disease; Pain; Peripheral Nervous System Diseases; Polyneuropathy	Drug: Ranolazine; Drug: Placebo	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 5 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Double-blind, Placebo-controlled, Cross-over Study of Ranolazine in Patients With Coronary Artery Disease for the Treatment of Painful Polyneuropathy
• Study Start Date: Jan 1, 2009
• Actual Primary Completion Date: Jun 1, 2009
• Actual Study Completion Date: Jun 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Placebo-Ranolazine Participants were randomized to receive placebo to match ranolazine during Weeks 1 to 6, then ranolazine during Weeks 7 to 12.	Drug: Ranolazine; Ranolazine ER tablet administered orally for 6 weeks (500 mg twice a day for 3 weeks, followed by either 500 mg or 1000 mg twice a day for 3 weeks).; Other Names: Ranexa ; Drug: Placebo; Placebo to match ranolazine administered twice a day for 6 weeks
Experimental: Ranolazine-Placebo Participants were randomized to receive ranolazine during Weeks 1 to 6, then placebo to match ranolazine during Weeks 7 to 12.	Drug: Ranolazine; Ranolazine ER tablet administered orally for 6 weeks (500 mg twice a day for 3 weeks, followed by either 500 mg or 1000 mg twice a day for 3 weeks).; Other Names: Ranexa ; Drug: Placebo; Placebo to match ranolazine administered twice a day for 6 weeks

Outcome Measures

Primary Outcome Measures

1. Reduction in Neuropathic Pain [Baseline to Week 6]

   Reduction in patient-reported neuropathic pain (by 2 numeric levels as measured by the Numeric Pain Scale)

Secondary Outcome Measures

1. Assess Participant Quality of Life Utilizing the Short Form 36 Health Survey (SF-36v2) Questionnaire [Baseline to Week 6]

   The participant quality of life assessed utilizing the SF-36v2 questionnaire

2. Response to Thermal and Mechanical Stimuli [Baseline to Week 6]

   The participant response to thermal and mechanical stimuli as measured by the Hargreaves and Von Frey tests

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Males or females aged ≥ 18 years

• Coronary artery disease with a clinically diagnosed peripheral neuropathy

• Willing and able to provide signed informed consent and Health Insurance Portability and Accountability Act (HIPAA) authorization

• Willing and able to comply with the requirements of the protocol and follow directions from the clinic staff

Exclusion Criteria:

• History of allergy or intolerance to ranolazine

• Any condition or concomitant medication that would have precluded the safe use of ranolazine as outlined in the prescribing information sheet (see Appendix E)

• 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

• In the judgment of the investigator, clinically-significant abnormal physical findings during screening (excluding the patient's peripheral neuropathy condition)

• Use of any experimental or investigational drug or device within 30 days prior to screening

• Pregnant or breast feeding, or (if premenopausal), not practicing an acceptable method of birth control (as detailed in Inclusion Criterion 4)

• Had received prior treatment with, or investigational exposure to, ranolazine within 7 days prior to randomization

• Clinically significant hepatic impairment

• Had end-stage renal disease requiring dialysis

• Psychological or addictive disorders (not limited to, but including drug and/or alcohol dependency) that may have precluded patient consent or compliance, or that may have confounded study interpretation

• Positive pregnancy test at Baseline (pre-randomization, Day 0)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Cardiovascular Institute of the South Clinical Research Corporation	Houma	Louisiana	United States	70360

Sponsors and Collaborators

• Gilead Sciences

Investigators

• Principal Investigator: Craig Walker, MD, Cardiovascular Institute of the South Clinical Research Corporation

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• The Neuropathy Association, a public, non-profit organization providing information and support for patients with neuropathy

Publications

None provided.

• Responsible Party: Gilead Sciences
• ClinicalTrials.gov Identifier: NCT00832572
• Other Study ID Numbers: CVT 3042
• First Posted: Jan 30, 2009
• Last Update Posted: Jun 30, 2014
• Last Verified: May 1, 2014

• Keywords provided by Gilead Sciences: Coronary Artery Disease; Pain; Peripheral Neuropathy; Polyneuropathy
• Additional relevant MeSH terms: Nervous System Diseases; Polyneuropathies; Peripheral Nervous System Diseases; Coronary Artery Disease; Myocardial Ischemia; Coronary Disease; Ranolazine

Study Results

Participant Flow

Recruitment Details	Five participants were enrolled and treated.

Arm/Group Title	Placebo/Ranolazine	Ranolazine/Placebo
Arm/Group Description	Participants were randomized to receive placebo to match ranolazine during Weeks 1 to 6 (Period 1), then ranolazine (500 mg twice a day for 3 weeks, followed by either 500 mg or 1000 mg twice a day for 3 weeks) during Weeks 7 to 12 (Period 2).	Participants were randomized to receive ranolazine (500 mg twice a day for 3 weeks, followed by either 500 mg or 1000 mg twice a day for 3 weeks) during Weeks 1 to 6 (Period 1), then placebo to match ranolazine during Weeks 7 to 12 (Period 2).
Period Title: Period 1
STARTED	3	2
COMPLETED	3	2
NOT COMPLETED	0	0
Period Title: Period 1
STARTED	3	2
COMPLETED	3	2
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Placebo/Ranolazine	Ranolazine/Placebo	Total
Arm/Group Description	Participants were randomized to receive placebo to match ranolazine during Weeks 1 to 6 (Period 1), then ranolazine (500 mg twice a day for 3 weeks, followed by either 500 mg or 1000 mg twice a day for 3 weeks) during Weeks 7 to 12 (Period 2).	Participants were randomized to receive ranolazine (500 mg twice a day for 3 weeks, followed by either 500 mg or 1000 mg twice a day for 3 weeks) during Weeks 1 to 6 (Period 1), then placebo to match ranolazine during Weeks 7 to 12 (Period 2).	Total of all reporting groups
Overall Participants	3	2	5
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	0 0%	2 100%	2 40%
>=65 years	3 100%	0 0%	3 60%
Sex: Female, Male (Count of Participants)
Female	1 33.3%	1 50%	2 40%
Male	2 66.7%	1 50%	3 60%

Outcome Measures

1. Primary Outcome

Title	Reduction in Neuropathic Pain
Description	Reduction in patient-reported neuropathic pain (by 2 numeric levels as measured by the Numeric Pain Scale)
Time Frame	Baseline to Week 6

Outcome Measure Data

Analysis Population Description

Study was stopped and no analysis was performed on the primary outcome measure.

Arm/Group Title	Placebo/Ranolazine	Ranolazine/Placebo
Arm/Group Description	Participants were randomized to receive placebo to match ranolazine during Weeks 1 to 6 (Period 1), then ranolazine (500 mg twice a day for 3 weeks, followed by either 500 mg or 1000 mg twice a day for 3 weeks) during Weeks 7 to 12 (Period 2).	Participants were randomized to receive ranolazine (500 mg twice a day for 3 weeks, followed by either 500 mg or 1000 mg twice a day for 3 weeks) during Weeks 1 to 6 (Period 1), then placebo to match ranolazine during Weeks 7 to 12 (Period 2).
Measure Participants	0	0

2. Secondary Outcome

Title	Assess Participant Quality of Life Utilizing the Short Form 36 Health Survey (SF-36v2) Questionnaire
Description	The participant quality of life assessed utilizing the SF-36v2 questionnaire
Time Frame	Baseline to Week 6

Outcome Measure Data

Analysis Population Description

Study was stopped and no analyses were performed on the secondary outcome measures.

Arm/Group Title	Placebo/Ranolazine	Ranolazine/Placebo
Arm/Group Description	Participants were randomized to receive placebo to match ranolazine during Weeks 1 to 6 (Period 1), then ranolazine (500 mg twice a day for 3 weeks, followed by either 500 mg or 1000 mg twice a day for 3 weeks) during Weeks 7 to 12 (Period 2).	Participants were randomized to receive ranolazine (500 mg twice a day for 3 weeks, followed by either 500 mg or 1000 mg twice a day for 3 weeks) during Weeks 1 to 6 (Period 1), then placebo to match ranolazine during Weeks 7 to 12 (Period 2).
Measure Participants	0	0

3. Secondary Outcome

Title	Response to Thermal and Mechanical Stimuli
Description	The participant response to thermal and mechanical stimuli as measured by the Hargreaves and Von Frey tests
Time Frame	Baseline to Week 6

Outcome Measure Data

Analysis Population Description

Study was stopped and no analyses were performed on the secondary outcome measures.

Arm/Group Title	Placebo/Ranolazine	Ranolazine/Placebo
Arm/Group Description	Participants were randomized to receive placebo to match ranolazine during Weeks 1 to 6 (Period 1), then ranolazine (500 mg twice a day for 3 weeks, followed by either 500 mg or 1000 mg twice a day for 3 weeks) during Weeks 7 to 12 (Period 2).	Participants were randomized to receive ranolazine (500 mg twice a day for 3 weeks, followed by either 500 mg or 1000 mg twice a day for 3 weeks) during Weeks 1 to 6 (Period 1), then placebo to match ranolazine during Weeks 7 to 12 (Period 2).
Measure Participants	0	0

Adverse Events

Time Frame	Up to 12 weeks
Arm/Group Title	Placebo/Ranolazine, Period 1		Placebo/Ranolazine, Period 2		Ranolazine/Placebo, Period 1		Ranolazine/Placebo, Period 2
Arm/Group Description	Adverse events for this reporting group are those occurring during Period 1 (participants were receiving placebo). Participants were randomized to receive placebo to match ranolazine during Weeks 1 to 6 (Period 1), then ranolazine (500 mg twice a day for 3 weeks, followed by either 500 mg or 1000 mg twice a day for 3 weeks) during Weeks 7 to 12 (Period 2).		Adverse events for this reporting group are those occurring during Period 2 (participants were receiving ranolazine). Participants were randomized to receive placebo to match ranolazine during Weeks 1 to 6 (Period 1), then ranolazine (500 mg twice a day for 3 weeks, followed by either 500 mg or 1000 mg twice a day for 3 weeks) during Weeks 7 to 12 (Period 2).		Adverse events for this reporting group are those occurring during Period 1 (participants were receiving ranolazine). Participants were randomized to receive ranolazine (500 mg twice a day for 3 weeks, followed by either 500 mg or 1000 mg twice a day for 3 weeks) during Weeks 1 to 6 (Period 1), then placebo to match ranolazine during Weeks 7 to 12 (Period 2).		Adverse events for this reporting group are those occurring during Period 2 (participants were receiving placebo). Participants were randomized to receive ranolazine (500 mg twice a day for 3 weeks, followed by either 500 mg or 1000 mg twice a day for 3 weeks) during Weeks 1 to 6 (Period 1), then placebo to match ranolazine during Weeks 7 to 12 (Period 2).
All Cause Mortality
	Placebo/Ranolazine, Period 1		Placebo/Ranolazine, Period 2		Ranolazine/Placebo, Period 1		Ranolazine/Placebo, Period 2
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo/Ranolazine, Period 1		Placebo/Ranolazine, Period 2		Ranolazine/Placebo, Period 1		Ranolazine/Placebo, Period 2
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/3 (0%)		0/3 (0%)		0/2 (0%)		0/2 (0%)
Other (Not Including Serious) Adverse Events
	Placebo/Ranolazine, Period 1		Placebo/Ranolazine, Period 2		Ranolazine/Placebo, Period 1		Ranolazine/Placebo, Period 2
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/3 (33.3%)		0/3 (0%)		0/2 (0%)		1/2 (50%)
General disorders
Fever	0/3 (0%)		0/3 (0%)		0/2 (0%)		1/2 (50%)
Chills	0/3 (0%)		0/3 (0%)		0/2 (0%)		1/2 (50%)
Musculoskeletal and connective tissue disorders
Right leg muscle tendon pulled	0/3 (0%)		0/3 (0%)		0/2 (0%)		1/2 (50%)
Stabbing pain to right leg calf	0/3 (0%)		0/3 (0%)		0/2 (0%)		1/2 (50%)
Aching pain to right calf	0/3 (0%)		0/3 (0%)		0/2 (0%)		1/2 (50%)
Expiratory wheezing	1/3 (33.3%)		0/3 (0%)		0/2 (0%)		0/2 (0%)
Nervous system disorders
Headache	0/3 (0%)		0/3 (0%)		0/2 (0%)		1/2 (50%)
Sensitivity to light (eyes)	0/3 (0%)		0/3 (0%)		0/2 (0%)		1/2 (50%)

Limitations/Caveats

The study was stopped after 5 participants were enrolled. No outcome measure analyses were performed. Adverse events were collected and reported to the study center's Institutional Review Board.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

After conclusion of the study and without prior written approval from Gilead, investigators in this study may communicate, orally present, or publish in scientific journals or other media only after the following conditions have been met: The results of the study in their entirety have been publicly disclosed by or with the consent of Gilead in an abstract, manuscript, or presentation form; or The study has been completed at all study sites for at least 2 years