Ranolazine When Added to Glimepiride in Subjects With Type 2 Diabetes Mellitus

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences
ClinicalTrials.gov Identifier:
NCT01494987
First received: December 15, 2011
Last updated: August 21, 2014
Last verified: August 2014
Results First Received: August 21, 2014  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Investigator);   Primary Purpose: Treatment
Condition: Type 2 Diabetes Mellitus
Interventions: Drug: Ranolazine
Drug: Placebo
Drug: Glimepiride
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 103 study sites in Asia, Europe, South Africa, and the United States. The first participant was screened on 12 January 2012. The last participant observation occurred on 28 August 2013.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
595 participants entered the qualifying period (355 required and completed the glimepiride stabilization period); 431 were randomized and treated (Safety Analysis Set). Of these, 14 were excluded due to major eligibility criteria protocol violation or had no baseline or ontreatment data; thus, 417 were included in the Full Analysis Set.

Reporting Groups
  Description
Placebo+Glimepiride

Glimepiride stabilization period (up to 8 weeks): participants not on stable glimepiride received glimepiride 2 mg once daily, and if tolerated the dose was increased on Day 8 (+ 2 days) to 4 mg once daily.

Qualifying period: participants received placebo to match ranolazine twice daily in addition to glimepiride for 14 days (+ 2 days) and if ≥ 80% compliant and meeting eligibility criteria continued to the treatment period.

Treatment period: participants were randomized to receive placebo to match ranolazine plus glimepiride 4 mg once daily for 24 weeks.

Participants were required to maintain their diet and exercise regimen.

Ranolazine+Glimepiride

Glimepiride stabilization period (up to 8 weeks): participants not on stable glimepiride received glimepiride 2 mg once daily, and if tolerated the dose was increased on Day 8 (+ 2 days) to 4 mg once daily.

Qualifying period: participants received placebo to match ranolazine twice daily in addition to glimepiride for 14 days (+ 2 days) and if ≥ 80% compliant and meeting eligibility criteria continued to the treatment period.

Treatment period: participants were randomized to receive ranolazine (1 x 500 mg tablet) twice daily plus glimepiride 4 mg once daily on Days 1 through 7, followed by ranolazine 1000 mg (2 x 500 mg tablets) twice daily plus glimepiride 4 mg once daily from Day 8 (or by Day 16 if not well tolerated) through Week 24.

Participants were required to maintain their diet and exercise regimen.


Participant Flow:   Overall Study
    Placebo+Glimepiride     Ranolazine+Glimepiride  
STARTED     216     215  
COMPLETED     188     187  
NOT COMPLETED     28     28  
Adverse Event                 6                 5  
Hyperglycemia                 6                 4  
Investigator's Discretion                 1                 2  
Lost to Follow-up                 1                 1  
Protocol Violation                 3                 3  
Subject Non-Compliance                 9                 10  
Subject Withdrew Consent                 2                 3  



  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.
Baseline characteristics are reported for the Safety Analysis Set following randomization. The Safety Analysis Set includes randomized participants who received at least one dose of study treatment.

Reporting Groups
  Description
Placebo+Glimepiride

Glimepiride stabilization period (up to 8 weeks): participants not on stable glimepiride received glimepiride 2 mg once daily, and if tolerated the dose was increased on Day 8 (+ 2 days) to 4 mg once daily.

Qualifying period: participants received placebo to match ranolazine twice daily in addition to glimepiride for 14 days (+ 2 days) and if ≥ 80% compliant and meeting eligibility criteria continued to the treatment period.

Treatment period: participants were randomized to receive placebo to match ranolazine plus glimepiride 4 mg once daily for 24 weeks.

Participants were required to maintain their diet and exercise regimen.

Ranolazine+Glimepiride

Glimepiride stabilization period (up to 8 weeks): participants not on stable glimepiride received glimepiride 2 mg once daily, and if tolerated the dose was increased on Day 8 (+ 2 days) to 4 mg once daily.

Qualifying period: participants received placebo to match ranolazine twice daily in addition to glimepiride for 14 days (+ 2 days) and if ≥ 80% compliant and meeting eligibility criteria continued to the treatment period.

Treatment period: participants were randomized to receive ranolazine (1 x 500 mg tablet) twice daily plus glimepiride 4 mg once daily on Days 1 through 7, followed by ranolazine 1000 mg (2 x 500 mg tablets) twice daily plus glimepiride 4 mg once daily from Day 8 (or by Day 16 if not well tolerated) through Week 24.

Participants were required to maintain their diet and exercise regimen.

Total Total of all reporting groups

Baseline Measures
    Placebo+Glimepiride     Ranolazine+Glimepiride     Total  
Number of Participants  
[units: participants]
  216     215     431  
Age  
[units: years]
Mean ± Standard Deviation
  59  ± 8.6     59  ± 8.8     59  ± 8.7  
Gender  
[units: participants]
     
Female     123     120     243  
Male     93     95     188  
Ethnicity (NIH/OMB)  
[units: participants]
     
Hispanic or Latino     32     32     64  
Not Hispanic or Latino     181     182     363  
Unknown or Not Reported     3     1     4  
Race/Ethnicity, Customized  
[units: participants]
     
American Indian or Alaska Native     1     0     1  
Asian     4     3     7  
Black or African American     10     3     13  
Native Hawaiian or Other Pacific Islander     1     0     1  
White     198     204     402  
Other     2     5     7  
Region of Enrollment  
[units: participants]
     
Serbia     4     0     4  
United States     61     60     121  
Czech Republic     1     0     1  
Hungary     4     6     10  
Slovakia     1     2     3  
Poland     5     4     9  
Ukraine     26     27     53  
Romania     11     9     20  
South Africa     4     3     7  
Russian Federation     99     104     203  
Body Mass Index  
[units: kg/m^2]
Mean ± Standard Deviation
  32.8  ± 4.35     32.2  ± 3.88     32.5  ± 4.13  
Glycosylated hemoglobin (HbA1c)  
[units: percent HbA1c in blood]
Mean ± Standard Deviation
  8.10  ± 0.746     8.07  ± 0.776     8.08  ± 0.760  
Fasting Serum Glucose  
[units: mg/dL]
Mean ± Standard Deviation
  177.2  ± 34.27     177.4  ± 37.03     177.3  ± 35.63  
Duration of Diabetes [1]
[units: years]
Mean ± Standard Deviation
  7.0  ± 5.07     7.1  ± 4.92     7.0  ± 4.99  
Estimated glomerular filtration rate (eGFR)  
[units: mL/min/1.73m^2]
Mean ± Standard Deviation
  83.2  ± 18.77     81.2  ± 20.85     82.2  ± 19.84  
[1] Participants in the Safety Analysis Set with available data were analyzed (n = 215 in both groups).



  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 Incremental Change of 2-hour Postprandial Serum Glucose at Week 24   [ Time Frame: Baseline; Week 24 ]

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

4.  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


No publications provided


Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT01494987     History of Changes
Other Study ID Numbers: GS-US-259-0110
Study First Received: December 15, 2011
Results First Received: August 21, 2014
Last Updated: August 21, 2014
Health Authority: United States: Food and Drug Administration
Czech Republic: State Institute for Drug Control
Hungary: National Institute of Pharmacy
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Romania: National Medicines Agency
Russia: Ministry of Health of the Russian Federation
Serbia: Medicines and Medical Devices Agency
Slovakia: State Institute for Drug Control
South Africa: Medicines Control Council
Ukraine: Ministry of Health