Trial Outcomes & Findings for Effects of Nateglinide on Postprandial Glucose Excursion by Restoring Early Phase Insulin Secretion (NCT NCT01030952)

NCT ID: NCT01030952

Last Updated: 2012-10-19

Results Overview

The postprandial glucose area under the curve (AUC)was calculated using values from the 3 time points. Participants were fasting (no calorie intake for at least 8 hours prior to the meal test) and completed the standardized meal test between 7 and 10 AM. 0-4 hours AUC were calculated using trapezoid methods.

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 103 participants
• Primary outcome timeframe: 3 weeks (end of study) minus baseline
• Results posted on: 2012-10-19

Participant Flow

Participant milestones

Measure	Nateglinide 120 mg by mouth, three times daily 10 minutes immediately before 3 meals	Acarbose patients in Acarbose group received Acarbose 50 mg by mouth, three times daily with the first bite of a meal
Overall Study STARTED	51	52
Overall Study COMPLETED	49	49
Overall Study NOT COMPLETED	2	3

Reasons for withdrawal

Measure	Nateglinide 120 mg by mouth, three times daily 10 minutes immediately before 3 meals	Acarbose patients in Acarbose group received Acarbose 50 mg by mouth, three times daily with the first bite of a meal
Overall Study Protocol Violation	0	1
Overall Study Informed consent withdrawal	1	0
Overall Study Lost to Follow-up	0	1
Overall Study Unexplained	1	1

Baseline Characteristics

Effects of Nateglinide on Postprandial Glucose Excursion by Restoring Early Phase Insulin Secretion

Baseline characteristics by cohort

Measure	Nateglinide n=51 Participants 120 mg by mouth, three times daily 10 minutes immediately before 3 meals	Acarbose n=52 Participants patients in Acarbose group received Acarbose 50 mg by mouth, three times daily with the first bite of a meal	Total n=103 Participants Total of all reporting groups
Age Continuous	53.4 years STANDARD_DEVIATION 10.34 • n=5 Participants	53.7 years STANDARD_DEVIATION 9.36 • n=7 Participants	53.5 years STANDARD_DEVIATION 9.81 • n=5 Participants
Sex: Female, Male Female	20 Participants 39.22 • n=5 Participants	23 Participants 44.23 • n=7 Participants	43 Participants n=5 Participants
Sex: Female, Male Male	31 Participants 60.78 • n=5 Participants	29 Participants 55.7 • n=7 Participants	60 Participants n=5 Participants

PRIMARY outcome

Timeframe: 3 weeks (end of study) minus baseline

Population: Intent to Treat population - All patients who received at least one dose of study drug after random allocation and had at least one primary or secondary efficacy evaluation after baseline.

The postprandial glucose area under the curve (AUC)was calculated using values from the 3 time points. Participants were fasting (no calorie intake for at least 8 hours prior to the meal test) and completed the standardized meal test between 7 and 10 AM.

0-4 hours AUC were calculated using trapezoid methods.

Outcome measures

Measure	Nateglinide n=39 Participants 120 mg by mouth, three times daily (P.O. t.i.d) 10 minutes immediately before 3 meals	Acarbose n=42 Participants 50 mg by mouth, three times daily (P.O. t.i.d) with the first bite of a meal
Change in Area Under Curve of 0-4 Hours Postprandial Glucose (AUCpp0-4hours) in Standardized Meal Test Using Continuous Glucose Monitoring System (CGMS)	-9.20 millimoles hours per litre (mmol*hr/L) 95% Confidence Interval 11.71 • Interval -11.78 to -6.621	-9.92 millimoles hours per litre (mmol*hr/L) 95% Confidence Interval 9.97 • Interval -12.407 to -7.438

SECONDARY outcome

Timeframe: baseline, 3 weeks (end of study)

Population: Intent to Treat population - All patients who received at least one dose of study drug after random allocation and had at least one primary or secondary efficacy evaluation after baseline.

Incremental glucose peak (IGP) was the maximal incremental increase in blood glucose obtained at any point after meal

Outcome measures

Measure	Nateglinide n=51 Participants 120 mg by mouth, three times daily (P.O. t.i.d) 10 minutes immediately before 3 meals	Acarbose n=52 Participants 50 mg by mouth, three times daily (P.O. t.i.d) with the first bite of a meal
Change in Incremental Glucose Peak (IGP) From Baseline	-2.72 millimoles per litre (mmol/L) Standard Deviation 2.86	-1.89 millimoles per litre (mmol/L) Standard Deviation 2.76

SECONDARY outcome

Timeframe: baseline and at 3 weeks (end of study)

Population: Intent to Treat population - All patients who received at least one dose of study drug after random allocation and had at least one primary or secondary efficacy evaluation after baseline

The 24 hour mean blood glucose (MBG) level was calculated as the mean of all the consecutive readings on baseline and end of study(3 weeks later) separately.

Outcome measures

Measure	Nateglinide n=51 Participants 120 mg by mouth, three times daily (P.O. t.i.d) 10 minutes immediately before 3 meals	Acarbose n=52 Participants 50 mg by mouth, three times daily (P.O. t.i.d) with the first bite of a meal
Change in Mean Blood Glucose (MBG)	-1.16 millimoles per litre (mmol/l) Standard Deviation 1.24	-0.78 millimoles per litre (mmol/l) Standard Deviation 1.29

SECONDARY outcome

Timeframe: baseline, 3 weeks (end of study)

Population: Intent to Treat population - All patients who received at least one dose of study drug after random allocation and had at least one primary or secondary efficacy evaluation after baseline

Change in standard deviation (SD) from baseline of mean blood glucose (MBG) describes the range of blood glucose fluctuation over 24 hours.

Outcome measures

Measure	Nateglinide n=51 Participants 120 mg by mouth, three times daily (P.O. t.i.d) 10 minutes immediately before 3 meals	Acarbose n=52 Participants 50 mg by mouth, three times daily (P.O. t.i.d) with the first bite of a meal
Change in Standard Deviation (SD) From Baseline of Mean Blood Glucose (MBG) Over 24 Hours.	-0.48 mmol/l Standard Deviation 0.63	-0.63 mmol/l Standard Deviation 0.59

SECONDARY outcome

Timeframe: baseline, 3 weeks (end of study)

Population: Intent-to treat population (ITT): All randomized participants who received at least 1 dose of study drug, had valid baseline data, and at least 1 post-baseline assessment of the primary efficacy variable.

The mean of the daily differences (MODD), calculated as the average absolute difference of paired glucose values during two successive 24 hour periods, was used to assess day-to-day glycaemic variability.

Outcome measures

Measure	Nateglinide n=51 Participants 120 mg by mouth, three times daily (P.O. t.i.d) 10 minutes immediately before 3 meals	Acarbose n=52 Participants 50 mg by mouth, three times daily (P.O. t.i.d) with the first bite of a meal
Change in Mean of Daily Difference of Paired Blood Glucose Value (MODD)	-0.06 millimoles per litre (mmol/l) Standard Deviation 0.95	-0.21 millimoles per litre (mmol/l) Standard Deviation 0.86

SECONDARY outcome

Timeframe: baseline, end of study (3 weeks)

Population: Intent-to treat population (ITT): All randomized participants who received at least 1 dose of study drug, had valid baseline data, and at least 1 post-baseline assessment of the primary efficacy variable.

Blood samples were collected for measurement of plasma glucose at 30, 60, 90, and 120 minutes following the start of a standardized meal test at Baseline and Week 4. The postprandial glucose area under the curve was calculated using values from the 4 time points. Participants were fasting (no calorie intake for at least 8 hours prior to the meal test) and completed the standardized meal test between 7 and 10 AM.

Outcome measures

Measure	Nateglinide n=51 Participants 120 mg by mouth, three times daily (P.O. t.i.d) 10 minutes immediately before 3 meals	Acarbose n=52 Participants 50 mg by mouth, three times daily (P.O. t.i.d) with the first bite of a meal
Changes in 24 Hour Glucose Area Under Curve (AUCpp)	-1.16 mmol*min/L Standard Deviation 1.24	-0.78 mmol*min/L Standard Deviation 1.29

SECONDARY outcome

Timeframe: baseline, 3 weeks (end of study)

Population: Intent to Treat population - All patients who received at least one dose of study drug after random allocation and had at least one primary or secondary efficacy evaluation after baseline. During different time points, participants with observations at that time point were included in the analysis.

GSA levels were to be determined by CGMS at 7:00~10:00 am in the 4-hour standardized meal test before treatment after overnight fasting for efficacy assessments

Outcome measures

Measure	Nateglinide n=51 Participants 120 mg by mouth, three times daily (P.O. t.i.d) 10 minutes immediately before 3 meals	Acarbose n=51 Participants 50 mg by mouth, three times daily (P.O. t.i.d) with the first bite of a meal
Change in Glycated Serum Albumin (GSA) Levels From Baseline After Treatment	-2.22 percent Standard Deviation 1.90	-1.74 percent Standard Deviation 1.50

SECONDARY outcome

Timeframe: baseline, 3 weeks (end of study)

Population: The Intent to Treat (ITT) population consists of all patients randomized and who have at least one dose of study medication.

This outcome measure calculated the change in insulin levels between groups over time at 0, 30 then 120 minutes

Outcome measures

Measure	Nateglinide n=51 Participants 120 mg by mouth, three times daily (P.O. t.i.d) 10 minutes immediately before 3 meals	Acarbose n=52 Participants 50 mg by mouth, three times daily (P.O. t.i.d) with the first bite of a meal
Change in Insulin Levels (μU/ml) During Standardized Meal Test at Endpoint From Baseline 30 minutes	13.87 (μU/ml) Standard Deviation 20.98	-6.64 (μU/ml) Standard Deviation 6.44
Change in Insulin Levels (μU/ml) During Standardized Meal Test at Endpoint From Baseline 0 minutes	0.32 (μU/ml) Standard Deviation 5.88	-0.21 (μU/ml) Standard Deviation 3.16
Change in Insulin Levels (μU/ml) During Standardized Meal Test at Endpoint From Baseline 120 minutes	15.03 (μU/ml) Standard Deviation 31.22	-16.24 (μU/ml) Standard Deviation 22.01

SECONDARY outcome

Timeframe: baseline, 3 weeks (end of study)

Population: Intent to Treat population - All patients who received at least one dose of study drug after random allocation and had at least one primary or secondary efficacy evaluation after baseline. During different time points, participants with observations at that time point were included in the analysis.

change in LDL-C at 0, 30 and 120 minutes

Outcome measures

Measure	Nateglinide n=51 Participants 120 mg by mouth, three times daily (P.O. t.i.d) 10 minutes immediately before 3 meals	Acarbose n=52 Participants 50 mg by mouth, three times daily (P.O. t.i.d) with the first bite of a meal
Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) 0 minutes	-0.04 millimoles per litre (mmol/l) Standard Deviation 0.65	0.064 millimoles per litre (mmol/l) Standard Deviation 0.44
Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) 30 minutes	-0.06 millimoles per litre (mmol/l) Standard Deviation 0.63	0.09 millimoles per litre (mmol/l) Standard Deviation 0.44
Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) 120 minutes	-0.04 millimoles per litre (mmol/l) Standard Deviation 0.56	0.13 millimoles per litre (mmol/l) Standard Deviation 0.42

SECONDARY outcome

Timeframe: baseline, 3 weeks (end of study)

Population: The Intent to Treat (ITT) population consists of all patients randomized and who have at least one dose of study medication.

time to change in Total Cholesterol blood lipids level at 0, 30, 120 minutes

Outcome measures

Measure	Nateglinide n=51 Participants 120 mg by mouth, three times daily (P.O. t.i.d) 10 minutes immediately before 3 meals	Acarbose n=52 Participants 50 mg by mouth, three times daily (P.O. t.i.d) with the first bite of a meal
Change of Total Cholesterol in Blood Lipids Levels During Standardized Meal Test at Endpoint From Baseline at Each Time Point 30 minutes	-0.06 millimoles per litre (mmol/l) Standard Deviation 0.70	0.56 millimoles per litre (mmol/l) Standard Deviation 0.04
Change of Total Cholesterol in Blood Lipids Levels During Standardized Meal Test at Endpoint From Baseline at Each Time Point 0 minutes	-0.03 millimoles per litre (mmol/l) Standard Deviation 0.67	-0.09 millimoles per litre (mmol/l) Standard Deviation 0.55
Change of Total Cholesterol in Blood Lipids Levels During Standardized Meal Test at Endpoint From Baseline at Each Time Point 120 minutes	-0.01 millimoles per litre (mmol/l) Standard Deviation 0.61	0.03 millimoles per litre (mmol/l) Standard Deviation 0.68

SECONDARY outcome

Timeframe: baseline, 3 weeks (end of study)

Population: The Intent to Treat (ITT) population consists of all patients randomized and who have at least one dose of study medication.

TG change in blood lipids level from baseline to endpoint

Outcome measures

Measure	Nateglinide n=51 Participants 120 mg by mouth, three times daily (P.O. t.i.d) 10 minutes immediately before 3 meals	Acarbose n=52 Participants 50 mg by mouth, three times daily (P.O. t.i.d) with the first bite of a meal
Change in Triglyceride (TG)Levels in Blood Lipid Levels During Standardized Meal Test at Endpoint 0 minutes	-0.19 millimoles per litre (mmol/l) Standard Deviation 0.63	-0.48 millimoles per litre (mmol/l) Standard Deviation 1.16
Change in Triglyceride (TG)Levels in Blood Lipid Levels During Standardized Meal Test at Endpoint 30 minutes	-0.23 millimoles per litre (mmol/l) Standard Deviation 0.68	-0.39 millimoles per litre (mmol/l) Standard Deviation 0.81
Change in Triglyceride (TG)Levels in Blood Lipid Levels During Standardized Meal Test at Endpoint 120 minutes	-0.19 millimoles per litre (mmol/l) Standard Deviation 0.83	-0.47 millimoles per litre (mmol/l) Standard Deviation 1.02

SECONDARY outcome

Timeframe: baseline, 3 weeks (end of study)

Population: Intent to Treat population - All patients who received at least one dose of study drug after random allocation and had at least one primary or secondary efficacy evaluation after baseline. During different time points, participants with observations at that time point were included in the analysis.

Blood samples were collected for measurement of HDL-C prior to (fasting) and 120 minutes following the start of a standardized meal test at Baseline and Week 3. Participants were fasting (no calorie intake for at least 8 hours prior to the meal test) and completed the standardized meal test between 7 and 10 AM. HDL-C was assessed at each study site using the same method and same reference value.

Outcome measures

Measure	Nateglinide n=51 Participants 120 mg by mouth, three times daily (P.O. t.i.d) 10 minutes immediately before 3 meals	Acarbose n=52 Participants 50 mg by mouth, three times daily (P.O. t.i.d) with the first bite of a meal
Change From Baseline in High-density Lipoprotein Cholesterol (HDL-C) at the End of the Study 0 minutes	0.20 millimoles per litre (mmol/l) Standard Deviation 0.10	-0.02 millimoles per litre (mmol/l) Standard Deviation 0.31
Change From Baseline in High-density Lipoprotein Cholesterol (HDL-C) at the End of the Study 30 minutes	0.02 millimoles per litre (mmol/l) Standard Deviation 0.10	0.01 millimoles per litre (mmol/l) Standard Deviation 0.16
Change From Baseline in High-density Lipoprotein Cholesterol (HDL-C) at the End of the Study 120 minutes	0.03 millimoles per litre (mmol/l) Standard Deviation 0.09	0.00 millimoles per litre (mmol/l) Standard Deviation 0.17

SECONDARY outcome

Timeframe: baseline, 3 weeks (end of study)

Population: Intent to Treat population - All patients who received at least one dose of study drug after random allocation and had at least one primary or secondary efficacy evaluation after baseline. During different time points, participants with observations at that time point were included in the analysis.

mean amplitude of glycaemic excursion (MAGE) is an average of the amplitudes of all glycemic excursions greater than a prespecified threshold size

Outcome measures

Measure	Nateglinide n=51 Participants 120 mg by mouth, three times daily (P.O. t.i.d) 10 minutes immediately before 3 meals	Acarbose n=52 Participants 50 mg by mouth, three times daily (P.O. t.i.d) with the first bite of a meal
Change in Mean Amplitude of Glycaemic Excursion (MAGE)	5.27 mmol/l Standard Deviation 2.09	5.03 mmol/l Standard Deviation 1.82

SECONDARY outcome

Timeframe: baseline, 3 weeks (end of study)

Population: Intent-to-treat population (ITT): All randomized participants who received at least 1 dose of study drug, had valid baseline data, and at least 1 post-baseline assessment of the primary efficacy variable. During different time points, participants with observations at that time point were included in the analysis

Measures/compares changes in percentage of hypoglycemia(<3.9mmol/l or <70 mg/dl) in glucose measurements in 24hours by continuous glucose monitoring system (CGMS) at endpoint from baseline between groups. Reported values are percent change of the base absolute values [100% * ((X-Y)/Y)]

Outcome measures

Measure	Nateglinide n=39 Participants 120 mg by mouth, three times daily (P.O. t.i.d) 10 minutes immediately before 3 meals	Acarbose n=42 Participants 50 mg by mouth, three times daily (P.O. t.i.d) with the first bite of a meal
The Percent of 24 Hour Hypoglycemic Measurements	0.82 percent of measurements Standard Deviation 2.22	-0.57 percent of measurements Standard Deviation 1.77

SECONDARY outcome

Timeframe: baseline, 3 weeks (end of study)

Population: Intent to Treat population - All patients who received at least one dose of study drug after random allocation and had at least one primary or secondary efficacy evaluation after baseline.

Measures/compares changes in percentage of hyperglycemia (>7.8mmol/l or 140 mg/dl) in glucose measurements in 24 hours by continuous glucose monitoring system (CGMS) at endpoint from baseline between groups. Reported values are percent change of the base absolute values [100% * ((X-Y)/Y)]

Outcome measures

Measure	Nateglinide n=39 Participants 120 mg by mouth, three times daily (P.O. t.i.d) 10 minutes immediately before 3 meals	Acarbose n=42 Participants 50 mg by mouth, three times daily (P.O. t.i.d) with the first bite of a meal
Change in Percent of 24 Hour Hyperglycemic Measurements	-50.83 percent of measurements Standard Deviation 64.62	-33.82 percent of measurements Standard Deviation 75.39

Adverse Events

Nateglinide

Serious events: 0 serious events

Other events: 7 other events

Deaths: 0 deaths

Acarbose

Serious events: 0 serious events

Other events: 16 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Nateglinide n=51 participants at risk 120 mg by mouth, three times daily (P.O. t.i.d) 10 minutes immediately before 3 meals	Acarbose n=52 participants at risk 50 mg by mouth, three times daily (P.O. t.i.d) with the first bite of a meal
Gastrointestinal disorders Abdominal distension	0.00% 0/51 • 3 weeks	7.7% 4/52 • 3 weeks
Gastrointestinal disorders Frequency bowel movements	0.00% 0/51 • 3 weeks	3.8% 2/52 • 3 weeks
Gastrointestinal disorders Gastrointestinal flatulence	0.00% 0/51 • 3 weeks	13.5% 7/52 • 3 weeks
Metabolism and nutrition disorders Hypoglycemia	5.9% 3/51 • 3 weeks	0.00% 0/52 • 3 weeks
Respiratory, thoracic and mediastinal disorders Upper respiratory tract infection	0.00% 0/51 • 3 weeks	3.8% 2/52 • 3 weeks
Investigations White blood cells count decrease	0.00% 0/51 • 3 weeks	1.9% 1/52 • 3 weeks
Investigations White blood cells count increase	2.0% 1/51 • 3 weeks	0.00% 0/52 • 3 weeks
Gastrointestinal disorders Diarrhoea	0.00% 0/51 • 3 weeks	1.9% 1/52 • 3 weeks
Hepatobiliary disorders Hepatic function abnormal	0.00% 0/51 • 3 weeks	1.9% 1/52 • 3 weeks
Infections and infestations Bronchopneumonia	0.00% 0/51 • 3 weeks	1.9% 1/52 • 3 weeks
Infections and infestations Oral herpes	2.0% 1/51 • 3 weeks	0.00% 0/52 • 3 weeks
Infections and infestations Urinary tract infection	0.00% 0/51 • 3 weeks	1.9% 1/52 • 3 weeks
Injury, poisoning and procedural complications Ulna fracture	2.0% 1/51 • 3 weeks	0.00% 0/52 • 3 weeks
Investigations White blood cells urine positive	0.00% 0/51 • 3 weeks	7.7% 4/52 • 3 weeks
Metabolism and nutrition disorders Diabetic ketoacidosis	2.0% 1/51 • 3 weeks	0.00% 0/52 • 3 weeks

Additional Information

Study Director

Novartis Pharmaceuticals

Phone: +1-800-244-7668

Results disclosure agreements

• Principal investigator is a sponsor employee The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial.
• Publication restrictions are in place

Restriction type: OTHER