Trial Outcomes & Findings for Effects of Nateglinide vs Acarbose on Postprandial Glucose Fluctuation, Dyslipidemia, and Inflammatory Factors (NCT NCT00928889)

NCT ID: NCT00928889

Last Updated: 2012-05-10

Results Overview

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. PPGE was defined as the mean difference between the preprandial glucose value and the postprandial glucose value measured at 2 hours in a standardized meal test. 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.

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 160 participants
• Primary outcome timeframe: Baseline to the end of the study (Week 4)
• Results posted on: 2012-05-10

Participant Flow

Participant milestones

Measure	Nateglinide 120 mg Nateglinide was taken orally 3 times daily, 10 minutes before meals for 4 weeks.	Acarbose 50 mg Acarbose 50 mg was taken orally 3 times daily, with the first bite of food at meals for 4 weeks.
Overall Study STARTED	80	80
Overall Study COMPLETED	75	78
Overall Study NOT COMPLETED	5	2

Reasons for withdrawal

Measure	Nateglinide 120 mg Nateglinide was taken orally 3 times daily, 10 minutes before meals for 4 weeks.	Acarbose 50 mg Acarbose 50 mg was taken orally 3 times daily, with the first bite of food at meals for 4 weeks.
Overall Study Lost to Follow-up	3	1
Overall Study Protocol Violation	0	1
Overall Study Adverse Event	1	0
Overall Study Other	1	0

Baseline Characteristics

Effects of Nateglinide vs Acarbose on Postprandial Glucose Fluctuation, Dyslipidemia, and Inflammatory Factors

Baseline characteristics by cohort

Measure	Nateglinide 120 mg n=80 Participants Nateglinide was taken orally 3 times daily, 10 minutes before meals for 4 weeks.	Acarbose 50 mg n=80 Participants Acarbose 50 mg was taken orally 3 times daily, with the first bite of food at meals for 4 weeks.	Total n=160 Participants Total of all reporting groups
Age Continuous	53.1 years STANDARD_DEVIATION 10.95 • n=93 Participants	51.9 years STANDARD_DEVIATION 10.82 • n=4 Participants	52.5 years STANDARD_DEVIATION 10.87 • n=27 Participants
Sex: Female, Male Female	40 Participants n=93 Participants	33 Participants n=4 Participants	73 Participants n=27 Participants
Sex: Female, Male Male	40 Participants n=93 Participants	47 Participants n=4 Participants	87 Participants n=27 Participants

PRIMARY outcome

Timeframe: Baseline to the end of the study (Week 4)

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. PPGE was defined as the mean difference between the preprandial glucose value and the postprandial glucose value measured at 2 hours in a standardized meal test. 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 120 mg n=74 Participants Nateglinide was taken orally 3 times daily, 10 minutes before meals for 4 weeks.	Acarbose 50 mg n=77 Participants Acarbose 50 mg was taken orally 3 times daily, with the first bite of food at meals for 4 weeks.
Change From Baseline in Postprandial Glucose Excursion (PPGE) at the End of the Study (Week 4)	-1.775 mmol/L Standard Deviation 1.3618	-2.434 mmol/L Standard Deviation 1.4418

SECONDARY outcome

Timeframe: Baseline to the end of the study (Week 4)

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 peak postprandial glucose values were used in the calculation of change from Baseline at Week 4. 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 120 mg n=74 Participants Nateglinide was taken orally 3 times daily, 10 minutes before meals for 4 weeks.	Acarbose 50 mg n=77 Participants Acarbose 50 mg was taken orally 3 times daily, with the first bite of food at meals for 4 weeks.
Change From Baseline in Peak Postprandial Glucose at the End of the Study (Week 4)	-2.350 mmol/L Standard Deviation 1.8480	-3.129 mmol/L Standard Deviation 1.8151

SECONDARY outcome

Timeframe: Baseline to the end of the study (Week 4)

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 120 mg n=74 Participants Nateglinide was taken orally 3 times daily, 10 minutes before meals for 4 weeks.	Acarbose 50 mg n=77 Participants Acarbose 50 mg was taken orally 3 times daily, with the first bite of food at meals for 4 weeks.
Change From Baseline in Postprandial Glucose Area Under the Curve at the End of the Study (Week 4)	-217.628 mmol*min/L Standard Deviation 179.8929	-278.447 mmol*min/L Standard Deviation 171.2480

SECONDARY outcome

Timeframe: Baseline to the end of the study (Week 4)

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 total cholesterol prior to (fasting) and 120 minutes following the start of a standardized meal test at Baseline and Week 4. 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. Total cholesterol was assessed at each study site using the same method and same reference value.

Outcome measures

Measure	Nateglinide 120 mg n=74 Participants Nateglinide was taken orally 3 times daily, 10 minutes before meals for 4 weeks.	Acarbose 50 mg n=77 Participants Acarbose 50 mg was taken orally 3 times daily, with the first bite of food at meals for 4 weeks.
Change From Baseline in Total Cholesterol at the End of the Study (Week 4) Fasting, N=74, 77	0.015 mmol/L Standard Deviation 0.742	-0.149 mmol/L Standard Deviation 1.050
Change From Baseline in Total Cholesterol at the End of the Study (Week 4) 120 minutes, N=74, 76	0.010 mmol/L Standard Deviation 0.700	-0.059 mmol/L Standard Deviation 0.682

SECONDARY outcome

Timeframe: Baseline to the end of the study (Week 4)

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 triglycerides prior to (fasting) and 120 minutes following the start of a standardized meal test at Baseline and Week 4. 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. Triglycerides were assessed at each study site using the same method and same reference value.

Outcome measures

Measure	Nateglinide 120 mg n=74 Participants Nateglinide was taken orally 3 times daily, 10 minutes before meals for 4 weeks.	Acarbose 50 mg n=77 Participants Acarbose 50 mg was taken orally 3 times daily, with the first bite of food at meals for 4 weeks.
Change From Baseline in Triglycerides at the End of the Study (Week 4) Fasting, N=74, 77	-0.010 mmol/L Standard Deviation 0.737	-0.418 mmol/L Standard Deviation 1.047
Change From Baseline in Triglycerides at the End of the Study (Week 4) 120 minutes, N=74, 76	0.026 mmol/L Standard Deviation 0.676	-0.396 mmol/L Standard Deviation 0.891

SECONDARY outcome

Timeframe: Baseline to the end of the study (Week 4)

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 LDL-C prior to (fasting) and 120 minutes following the start of a standardized meal test at Baseline and Week 4. 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. LDL-C was assessed at each study site using the same method and same reference value.

Outcome measures

Measure	Nateglinide 120 mg n=74 Participants Nateglinide was taken orally 3 times daily, 10 minutes before meals for 4 weeks.	Acarbose 50 mg n=77 Participants Acarbose 50 mg was taken orally 3 times daily, with the first bite of food at meals for 4 weeks.
Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) at the End of the Study (Week 4) Fasting, N=74, 77	0.036 mmol/L Standard Deviation 0.634	0.036 mmol/L Standard Deviation 0.570
Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) at the End of the Study (Week 4) 120 minutes, N=74, 76	-0.000 mmol/L Standard Deviation 0.604	0.044 mmol/L Standard Deviation 0.589

SECONDARY outcome

Timeframe: Baseline to the end of the study (Week 4)

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 HDL-C prior to (fasting) and 120 minutes following the start of a standardized meal test at Baseline and Week 4. 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 120 mg n=74 Participants Nateglinide was taken orally 3 times daily, 10 minutes before meals for 4 weeks.	Acarbose 50 mg n=77 Participants Acarbose 50 mg was taken orally 3 times daily, with the first bite of food at meals for 4 weeks.
Change From Baseline in High-density Lipoprotein Cholesterol (HDL-C) at the End of the Study (Week 4) Fasting, N=74, 77	0.020 mmol/L Standard Deviation 0.150	-0.039 mmol/L Standard Deviation 0.130
Change From Baseline in High-density Lipoprotein Cholesterol (HDL-C) at the End of the Study (Week 4) 120 minutes, N=74, 76	0.023 mmol/L Standard Deviation 0.246	0.003 mmol/L Standard Deviation 0.276

SECONDARY outcome

Timeframe: Baseline to the end of the study (Week 4)

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 FFA prior to (fasting) and 30, 60, 90, and 120 minutes following the start of a standardized meal test at Baseline and Week 4. 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. FFA was assayed at a central laboratory.

Outcome measures

Measure	Nateglinide 120 mg n=73 Participants Nateglinide was taken orally 3 times daily, 10 minutes before meals for 4 weeks.	Acarbose 50 mg n=75 Participants Acarbose 50 mg was taken orally 3 times daily, with the first bite of food at meals for 4 weeks.
Change From Baseline in Free Fatty Acids (FFA) at the End of the Study (Week 4) Fasting, N=73, 75	-0.048 mmol/L Standard Deviation 0.251	-0.040 mmol/L Standard Deviation 0.213
Change From Baseline in Free Fatty Acids (FFA) at the End of the Study (Week 4) 30 minutes, N=73, 75	-0.112 mmol/L Standard Deviation 0.427	-0.048 mmol/L Standard Deviation 0.363
Change From Baseline in Free Fatty Acids (FFA) at the End of the Study (Week 4) 60 minutes, N=72, 75	-0.224 mmol/L Standard Deviation 0.482	-0.048 mmol/L Standard Deviation 0.383
Change From Baseline in Free Fatty Acids (FFA) at the End of the Study (Week 4) 90 minutes, N=72, 75	-0.109 mmol/L Standard Deviation 0.438	-0.042 mmol/L Standard Deviation 0.419
Change From Baseline in Free Fatty Acids (FFA) at the End of the Study (Week 4) 120 minutes, N=73, 75	-0.099 mmol/L Standard Deviation 0.605	-0.034 mmol/L Standard Deviation 0.490

SECONDARY outcome

Timeframe: Baseline to the end of the study (Week 4)

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 hsCRP prior to (fasting) and 30, 60, 90, and 120 minutes following the start of a standardized meal test at Baseline and Week 4. 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. hsCRP was assayed at a central laboratory.

Outcome measures

Measure	Nateglinide 120 mg n=73 Participants Nateglinide was taken orally 3 times daily, 10 minutes before meals for 4 weeks.	Acarbose 50 mg n=75 Participants Acarbose 50 mg was taken orally 3 times daily, with the first bite of food at meals for 4 weeks.
Change From Baseline in High-sensitivity C-reactive Protein (hsCRP) at the End of the Study (Week 4) Fasting, N=73, 75	-0.229 mg/dL Standard Deviation 1.207	0.080 mg/dL Standard Deviation 0.404
Change From Baseline in High-sensitivity C-reactive Protein (hsCRP) at the End of the Study (Week 4) 30 minutes, N=73, 75	-0.227 mg/dL Standard Deviation 1.232	0.024 mg/dL Standard Deviation 0.135
Change From Baseline in High-sensitivity C-reactive Protein (hsCRP) at the End of the Study (Week 4) 60 minutes, N=72, 75	-0.219 mg/dL Standard Deviation 1.122	0.071 mg/dL Standard Deviation 0.398
Change From Baseline in High-sensitivity C-reactive Protein (hsCRP) at the End of the Study (Week 4) 90 minutes, N=72, 75	-0.220 mg/dL Standard Deviation 1.231	0.077 mg/dL Standard Deviation 0.394
Change From Baseline in High-sensitivity C-reactive Protein (hsCRP) at the End of the Study (Week 4) 120 minutes, N=72, 74	-0.218 mg/dL Standard Deviation 1.254	0.074 mg/dL Standard Deviation 0.375

SECONDARY outcome

Timeframe: Baseline to the end of the study (Week 4)

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 GSA prior to (fasting) the start of a standardized meal test at Baseline and Week 4. 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. GSA was assayed at a central laboratory.

Outcome measures

Measure	Nateglinide 120 mg n=72 Participants Nateglinide was taken orally 3 times daily, 10 minutes before meals for 4 weeks.	Acarbose 50 mg n=75 Participants Acarbose 50 mg was taken orally 3 times daily, with the first bite of food at meals for 4 weeks.
Change From Baseline in Glycosylated Serum Albumin (GSA) at the End of the Study (Week 4)	-1.2 Percentage Standard Deviation 1.57	-1.2 Percentage Standard Deviation 2.13

Adverse Events

Nateglinide 120 mg

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

Acarbose 50 mg

Serious events: 0 serious events

Other events: 7 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Nateglinide 120 mg n=80 participants at risk Nateglinide was taken orally 3 times daily, 10 minutes before meals for 4 weeks.	Acarbose 50 mg n=80 participants at risk Acarbose 50 mg was taken orally 3 times daily, with the first bite of food at meals for 4 weeks.
Gastrointestinal disorders Abdominal distension	1.2% 1/80 • Baseline to the end of the study (Week 4) Safety Population.	5.0% 4/80 • Baseline to the end of the study (Week 4) Safety Population.
Gastrointestinal disorders Flatulence	1.2% 1/80 • Baseline to the end of the study (Week 4) Safety Population.	5.0% 4/80 • Baseline to the end of the study (Week 4) Safety Population.
Metabolism and nutrition disorders Hypoglycaemia	5.0% 4/80 • Baseline to the end of the study (Week 4) Safety Population.	1.2% 1/80 • Baseline to the end of the study (Week 4) Safety Population.

Additional Information

Study Director

Novartis Pharmaceuticals

Phone: 862 778-8300

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 (ie, data from all sites) in the clinical trial.
• Publication restrictions are in place

Restriction type: OTHER