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A Phase 3 Study of Ranolazine in Subjects With Type 2 Diabetes Who Are Inadequately Controlled on Metformin Alone

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences
ClinicalTrials.gov Identifier:
NCT01555164
First received: March 13, 2012
Last updated: September 17, 2014
Last verified: September 2014
Results First Received: September 17, 2014  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Investigator);   Primary Purpose: Treatment
Condition: Type 2 Diabetes Mellitus
Interventions: Drug: Ranolazine
Drug: Placebo to match ranolazine
Drug: Metformin
Drug: Placebo to match metformin
Behavioral: Diet
Behavioral: Exercise

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Participants were enrolled (during the Qualifying Period) at a total of 112 study sites in Canada, Europe, Asia, Mexico, South Africa, and the United States. The first participant was screened on 28 June 2012. The last participant observation occurred on 01 October 2013.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
580 participants entered the qualifying period; 442 participants were randomized and treated, and comprise the Safety Analysis Set. Of these, 20 participants were excluded due to major eligibility criteria protocol violation or because the participant had no postbaseline data; the remaining 422 participants comprise the Full Analysis Set.

Reporting Groups
  Description
Placebo+Metformin

Qualifying period: Metformin 1000 mg (2 x 500 mg tablets) twice daily plus placebo to match ranolazine twice daily for either 2 or 8 weeks (dependent on metformin dose and HbA1c level at Screening) and participants who were ≥ 80% compliant and meeting eligibility criteria continued to the treatment period.

Treatment period: Metformin 1000 mg (2 x 500 mg tablets) twice daily plus placebo to match ranolazine twice daily through Week 24.

Participants were required to maintain their diet and exercise regimen.

Ranolazine+Metformin

Qualifying period: Metformin 1000 mg (2 x 500 mg tablets) twice daily plus placebo to match ranolazine twice daily for either 2 or 8 weeks (dependent on metformin dose and HbA1c level at Screening) and participants who were ≥ 80% compliant and meeting eligibility criteria continued to the treatment period.

Treatment period: Ranolazine 500 mg (1 x 500 mg tablet) twice daily plus metformin 500 mg/metformin placebo (1 x 500 mg tablet active metformin plus 1 placebo tablet) twice daily on Days 1 through 7, followed by ranolazine 1000 mg (2 x 500 mg tablets) twice daily plus metformin 500 mg/metformin placebo (1 x 500 mg tablet active metformin plus 1 placebo tablet) twice daily from Day 8 through Week 24.

Participants were required to maintain their diet and exercise regimen.


Participant Flow:   Overall Study
    Placebo+Metformin   Ranolazine+Metformin
STARTED   222   220 
COMPLETED   182   185 
NOT COMPLETED   40   35 
Adverse Event                5                7 
Hyperglycemia                0                1 
Investigator's Discretion                2                2 
Lost to Follow-up                4                3 
Protocol Violation                9                5 
Subject Non-compliance                14                6 
Subject Withdrew Consent                6                11 



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Safety Analysis Set: randomized participants who received at least one dose of study treatment.

Reporting Groups
  Description
Placebo+Metformin

Qualifying period: Metformin 1000 mg (2 x 500 mg tablets) twice daily plus placebo to match ranolazine twice daily for either 2 or 8 weeks (dependent on metformin dose and HbA1c level at Screening) and participants who were ≥ 80% compliant and meeting eligibility criteria continued to the treatment period.

Treatment period: Metformin 1000 mg (2 x 500 mg tablets) twice daily plus placebo to match ranolazine twice daily through Week 24.

Participants were required to maintain their diet and exercise regimen.

Ranolazine+Metformin

Qualifying period: Metformin 1000 mg (2 x 500 mg tablets) twice daily plus placebo to match ranolazine twice daily for either 2 or 8 weeks (dependent on metformin dose and HbA1c level at Screening) and participants who were ≥ 80% compliant and meeting eligibility criteria continued to the treatment period.

Treatment period: Ranolazine 500 mg (1 x 500 mg tablet) twice daily plus metformin 500 mg/metformin placebo (1 x 500 mg tablet active metformin plus 1 placebo tablet) twice daily on Days 1 through 7, followed by ranolazine 1000 mg (2 x 500 mg tablets) twice daily plus metformin 500 mg/metformin placebo (1 x 500 mg tablet active metformin plus 1 placebo tablet) twice daily from Day 8 through Week 24.

Participants were required to maintain their diet and exercise regimen.

Total Total of all reporting groups

Baseline Measures
   Placebo+Metformin   Ranolazine+Metformin   Total 
Overall Participants Analyzed 
[Units: Participants]
 222   220   442 
Age 
[Units: Years]
Mean (Standard Deviation)
 56  (8.9)   56  (9.3)   56  (9.1) 
Gender 
[Units: Participants]
     
Female   98   121   219 
Male   124   99   223 
Ethnicity (NIH/OMB) 
[Units: Participants]
     
Hispanic or Latino   53   37   90 
Not Hispanic or Latino   166   181   347 
Unknown or Not Reported   3   2   5 
Race/Ethnicity, Customized 
[Units: Participants]
     
American Indian or Alaska Native   2   0   2 
Asian   52   54   106 
Black or African American   8   11   19 
White   160   153   313 
Other   0   2   2 
Region of Enrollment 
[Units: Participants]
     
United States   82   67   149 
Hungary   8   8   16 
Czech Republic   0   1   1 
Mexico   6   4   10 
Canada   1   3   4 
Poland   0   5   5 
Ukraine   35   29   64 
South Africa   7   4   11 
Israel   2   1   3 
Russian Federation   37   49   86 
India   44   49   93 
Body Mass Index (BMI) 
[Units: Kg/m^2]
Mean (Standard Deviation)
 31.2  (4.46)   31.6  (4.95)   31.4  (4.71) 
Estimated glomerular filtration rate (eGFR) 
[Units: mL/min/1.73m^2]
Mean (Standard Deviation)
 90.8  (20.01)   89.9  (21.82)   90.4  (20.91) 
Glycosylated hemoglobin (HbA1c) 
[Units: Percent HbA1c in blood]
Mean (Standard Deviation)
 8.09  (0.729)   8.10  (0.692)   8.09  (0.710) 
Fasting Serum Glucose (FSG) 
[Units: mg/dL]
Mean (Standard Deviation)
 170.0  (35.97)   168.8  (32.86)   169.4  (34.42) 
Duration of Diabetes 
[Units: Years]
Mean (Standard Deviation)
 6.7  (5.31)   6.4  (5.37)   6.5  (5.34) 


  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 24   [ Time Frame: Baseline; Week 24 ]

2.  Secondary:   Change From Baseline in Fasting Serum Glucose at Week 24   [ Time Frame: Baseline; Week 24 ]

3.  Secondary:   Change From Baseline in 2-hour Postprandial Serum Glucose at Week 24   [ Time Frame: Baseline; Week 24 ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Clinical Trial Disclosures
Organization: Gilead Sciences, Inc.
e-mail: ClinicalTrialDisclosures@gilead.com



Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT01555164     History of Changes
Other Study ID Numbers: GS-US-259-0147
2012-001259-37 ( EudraCT Number )
Study First Received: March 13, 2012
Results First Received: September 17, 2014
Last Updated: September 17, 2014
Health Authority: United States: Food and Drug Administration
Canada: Health Canada
Russia: Ministry of Health of the Russian Federation
Ukraine: Ministry of Health
Czech Republic: State Institute for Drug Control
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Romania: National Agency for Medicines and Medical Devices
India: Drugs Controller General of India
Israel: Ministry of Health
South Africa: Medicines Control Council
South Korea: Korea Food and Drug Administration (KFDA)
Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica
Mexico: Ministry of Health