Trial Outcomes & Findings for A Phase 3 Study of Ranolazine in Subjects With Type 2 Diabetes Who Are Inadequately Controlled on Metformin Alone (NCT NCT01555164)
NCT ID: NCT01555164
Last Updated: 2014-09-23
Results Overview
The average (mean) change from baseline in HbA1c at Week 24 was analyzed.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
442 participants
Primary outcome timeframe
Baseline; Week 24
Results posted on
2014-09-23
Participant Flow
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.
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.
Participant milestones
| Measure |
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.
|
|---|---|---|
|
Overall Study
STARTED
|
222
|
220
|
|
Overall Study
COMPLETED
|
182
|
185
|
|
Overall Study
NOT COMPLETED
|
40
|
35
|
Reasons for withdrawal
| Measure |
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.
|
|---|---|---|
|
Overall Study
Adverse Event
|
5
|
7
|
|
Overall Study
Hyperglycemia
|
0
|
1
|
|
Overall Study
Investigator's Discretion
|
2
|
2
|
|
Overall Study
Lost to Follow-up
|
4
|
3
|
|
Overall Study
Protocol Violation
|
9
|
5
|
|
Overall Study
Subject Non-compliance
|
14
|
6
|
|
Overall Study
Subject Withdrew Consent
|
6
|
11
|
Baseline Characteristics
A Phase 3 Study of Ranolazine in Subjects With Type 2 Diabetes Who Are Inadequately Controlled on Metformin Alone
Baseline characteristics by cohort
| Measure |
Placebo+Metformin
n=222 Participants
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
n=220 Participants
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
n=442 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
56 years
STANDARD_DEVIATION 8.9 • n=5 Participants
|
56 years
STANDARD_DEVIATION 9.3 • n=7 Participants
|
56 years
STANDARD_DEVIATION 9.1 • n=5 Participants
|
|
Sex: Female, Male
Female
|
98 Participants
n=5 Participants
|
121 Participants
n=7 Participants
|
219 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
124 Participants
n=5 Participants
|
99 Participants
n=7 Participants
|
223 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
53 Participants
n=5 Participants
|
37 Participants
n=7 Participants
|
90 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
166 Participants
n=5 Participants
|
181 Participants
n=7 Participants
|
347 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
3 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
American Indian or Alaska Native
|
2 participants
n=5 Participants
|
0 participants
n=7 Participants
|
2 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Asian
|
52 participants
n=5 Participants
|
54 participants
n=7 Participants
|
106 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Black or African American
|
8 participants
n=5 Participants
|
11 participants
n=7 Participants
|
19 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
White
|
160 participants
n=5 Participants
|
153 participants
n=7 Participants
|
313 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Other
|
0 participants
n=5 Participants
|
2 participants
n=7 Participants
|
2 participants
n=5 Participants
|
|
Region of Enrollment
United States
|
82 participants
n=5 Participants
|
67 participants
n=7 Participants
|
149 participants
n=5 Participants
|
|
Region of Enrollment
Hungary
|
8 participants
n=5 Participants
|
8 participants
n=7 Participants
|
16 participants
n=5 Participants
|
|
Region of Enrollment
Czech Republic
|
0 participants
n=5 Participants
|
1 participants
n=7 Participants
|
1 participants
n=5 Participants
|
|
Region of Enrollment
Mexico
|
6 participants
n=5 Participants
|
4 participants
n=7 Participants
|
10 participants
n=5 Participants
|
|
Region of Enrollment
Canada
|
1 participants
n=5 Participants
|
3 participants
n=7 Participants
|
4 participants
n=5 Participants
|
|
Region of Enrollment
Poland
|
0 participants
n=5 Participants
|
5 participants
n=7 Participants
|
5 participants
n=5 Participants
|
|
Region of Enrollment
Ukraine
|
35 participants
n=5 Participants
|
29 participants
n=7 Participants
|
64 participants
n=5 Participants
|
|
Region of Enrollment
South Africa
|
7 participants
n=5 Participants
|
4 participants
n=7 Participants
|
11 participants
n=5 Participants
|
|
Region of Enrollment
Israel
|
2 participants
n=5 Participants
|
1 participants
n=7 Participants
|
3 participants
n=5 Participants
|
|
Region of Enrollment
Russian Federation
|
37 participants
n=5 Participants
|
49 participants
n=7 Participants
|
86 participants
n=5 Participants
|
|
Region of Enrollment
India
|
44 participants
n=5 Participants
|
49 participants
n=7 Participants
|
93 participants
n=5 Participants
|
|
Body Mass Index (BMI)
|
31.2 kg/m^2
STANDARD_DEVIATION 4.46 • n=5 Participants
|
31.6 kg/m^2
STANDARD_DEVIATION 4.95 • n=7 Participants
|
31.4 kg/m^2
STANDARD_DEVIATION 4.71 • n=5 Participants
|
|
Estimated glomerular filtration rate (eGFR)
|
90.8 mL/min/1.73m^2
STANDARD_DEVIATION 20.01 • n=5 Participants
|
89.9 mL/min/1.73m^2
STANDARD_DEVIATION 21.82 • n=7 Participants
|
90.4 mL/min/1.73m^2
STANDARD_DEVIATION 20.91 • n=5 Participants
|
|
Glycosylated hemoglobin (HbA1c)
|
8.09 percent HbA1c in blood
STANDARD_DEVIATION 0.729 • n=5 Participants
|
8.10 percent HbA1c in blood
STANDARD_DEVIATION 0.692 • n=7 Participants
|
8.09 percent HbA1c in blood
STANDARD_DEVIATION 0.710 • n=5 Participants
|
|
Fasting Serum Glucose (FSG)
|
170.0 mg/dL
STANDARD_DEVIATION 35.97 • n=5 Participants
|
168.8 mg/dL
STANDARD_DEVIATION 32.86 • n=7 Participants
|
169.4 mg/dL
STANDARD_DEVIATION 34.42 • n=5 Participants
|
|
Duration of Diabetes
|
6.7 years
STANDARD_DEVIATION 5.31 • n=5 Participants
|
6.4 years
STANDARD_DEVIATION 5.37 • n=7 Participants
|
6.5 years
STANDARD_DEVIATION 5.34 • n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline; Week 24Population: Participants in the Full Analysis Set (randomized participants who received ≥ 1 dose of study treatment with a baseline and at least one postbaseline measurement of HbA1c, excluding participants with major eligibility violations, and analyzed based on randomized treatment, regardless of actual treatment received) with available data were analyzed.
The average (mean) change from baseline in HbA1c at Week 24 was analyzed.
Outcome measures
| Measure |
Placebo+Metformin
n=174 Participants
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
n=179 Participants
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.
|
|---|---|---|
|
Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 24
HbA1c at Week 24
|
7.86 percent of HbA1c in blood
Standard Deviation 1.003
|
7.72 percent of HbA1c in blood
Standard Deviation 1.069
|
|
Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 24
Change from baseline in HbA1c at Week 24
|
-0.20 percent of HbA1c in blood
Standard Deviation 0.949
|
-0.37 percent of HbA1c in blood
Standard Deviation 0.916
|
SECONDARY outcome
Timeframe: Baseline; Week 24Population: Participants in the Full Analysis Set with available data were analyzed.
The average (mean) change from baseline in fasting serum glucose at Week 24 was analyzed.
Outcome measures
| Measure |
Placebo+Metformin
n=171 Participants
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
n=176 Participants
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.
|
|---|---|---|
|
Change From Baseline in Fasting Serum Glucose at Week 24
|
-3 mg/dL
Standard Deviation 44.7
|
3 mg/dL
Standard Deviation 42.5
|
SECONDARY outcome
Timeframe: Baseline; Week 24Population: Participants in the MMTT Full Analysis Set with available data were analyzed.
The average (mean) change from baseline in 2-hour postprandial serum glucose at Week 24 was analyzed. Mixed Meal Tolerance Test (MMTT) Full Analysis Set: randomized participants who received at least one dose of study treatment with a baseline and at least one postbaseline measurement of serum glucose at T=120 minutes during the MMTT, administered under fasting conditions, excluding participants with major eligibility protocol violations; analyzed based on the randomized treatment regardless of actual treatment received.
Outcome measures
| Measure |
Placebo+Metformin
n=166 Participants
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
n=173 Participants
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.
|
|---|---|---|
|
Change From Baseline in 2-hour Postprandial Serum Glucose at Week 24
|
-4 mg/dL
Standard Deviation 54.0
|
7 mg/dL
Standard Deviation 58.2
|
Adverse Events
Placebo+Metformin
Serious events: 2 serious events
Other events: 14 other events
Deaths: 0 deaths
Ranolazine+Metformin
Serious events: 3 serious events
Other events: 18 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Placebo+Metformin
n=222 participants at risk
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
n=220 participants at risk
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.
|
|---|---|---|
|
Cardiac disorders
Coronary artery disease
|
0.45%
1/222 • Up to 24 weeks plus 30 days
|
0.00%
0/220 • Up to 24 weeks plus 30 days
|
|
Cardiac disorders
Myocardial infarction
|
0.45%
1/222 • Up to 24 weeks plus 30 days
|
0.00%
0/220 • Up to 24 weeks plus 30 days
|
|
Gastrointestinal disorders
Impaired gastric emptying
|
0.00%
0/222 • Up to 24 weeks plus 30 days
|
0.45%
1/220 • Up to 24 weeks plus 30 days
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/222 • Up to 24 weeks plus 30 days
|
0.45%
1/220 • Up to 24 weeks plus 30 days
|
|
Injury, poisoning and procedural complications
Lower limb fracture
|
0.00%
0/222 • Up to 24 weeks plus 30 days
|
0.45%
1/220 • Up to 24 weeks plus 30 days
|
|
Metabolism and nutrition disorders
Metabolic acidosis
|
0.00%
0/222 • Up to 24 weeks plus 30 days
|
0.45%
1/220 • Up to 24 weeks plus 30 days
|
|
Musculoskeletal and connective tissue disorders
Spinal osteoarthritis
|
0.45%
1/222 • Up to 24 weeks plus 30 days
|
0.45%
1/220 • Up to 24 weeks plus 30 days
|
|
Musculoskeletal and connective tissue disorders
Lumbar spinal stenosis
|
0.00%
0/222 • Up to 24 weeks plus 30 days
|
0.45%
1/220 • Up to 24 weeks plus 30 days
|
Other adverse events
| Measure |
Placebo+Metformin
n=222 participants at risk
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
n=220 participants at risk
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.
|
|---|---|---|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
6.3%
14/222 • Up to 24 weeks plus 30 days
|
8.2%
18/220 • Up to 24 weeks plus 30 days
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee 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
- Publication restrictions are in place
Restriction type: OTHER