Study of the Durability of Glycemic Control With Nateglinide

• Sponsor: Ajou University School of Medicine (Other)
• Overall Status: Completed
• CT.gov ID: NCT00858013
• Collaborator: Korea University Guro Hospital (Other), Hanyang University (Other), Inha University Hospital (Other), Kyunghee University Medical Center (Other), Myongji Hospital (Other), Bundang CHA Hospital (Other), Wonju Severance Christian Hospital (Other), Hallym University Medical Center (Other)
• Enrollment: 88
• Locations: 7
• Arms: 2
• Actual Duration (Months): 62
• Patients Per Site: 12.6
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

This multi-center, randomized controlled study aims to evaluate the durability and efficacy of nateglinide therapy for long term glycemic control compared with glimepiride.

Condition or Disease	Intervention/Treatment	Phase
Type 2 Diabetes Mellitus	Drug: Nateglinide; Drug: Glimepiride	Phase 4

Detailed Description

Selected patients will be randomly assigned to receive nateglinide or glimepiride.

Previous treatment with oral antidiabetic drugs (metformin, a-glucosidase inhibitor, nateglinide or sulfonylurea) will be discontinued. After a 1 month wash-out period (if 6.5 ≤ HbA1c ≤ 8.5), patients will take randomly assigned drugs for 24 months.

Patients will be met by the trial investigator every 3 months following randomization. At each visit, patients whose HbA1c is > 8.0% will be retested 2 weeks later, and if the retested HbA1c is also above 8.0%, those patients will be withdrawn considering monotherapy failure. We will evaluate the durability of nateglinide in comparison with that of glimepiride based on the withdrawal rate.

Study Design

• Study Type: Interventional
• Actual Enrollment: 88 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Multi-center, Randomized, Open Label Study of the Durability of Glycemic Control With Nateglinide Versus Glimepiride as Monotherapy in Type 2 Diabetic Patients
• Actual Study Start Date: Apr 24, 2009
• Actual Primary Completion Date: Jun 25, 2014
• Actual Study Completion Date: Jun 25, 2014

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Nateglinide Nateglinide 90~120mg three times a day	Drug: Nateglinide; Nateglinide 90~120mg three times a day; Other Names: fastic
Active Comparator: Glimepiride Glimepiride 1~2mg once a day	Drug: Glimepiride; Glimepiride 1~2mg once a day; Other Names: amaryl

Outcome Measures

Primary Outcome Measures

1. The Durability of Nateglinide in Comparison With Those of Glimepiride Based on the Withdrawal Rate [every 3 months following randomization, for 24 months]

   % monotherapy failure, that means % number of participants who withdrew from the study due to high HbA1c (>8.0%)

Secondary Outcome Measures

1. HbA1c [at 24 months]

   HbA1c (%) at 24 months

2. Fasting Glucose [at 24 months]

   fasting glucose (mg/dL) at 24 months

3. C-peptide [at 24 months]

   c-peptide(uU/mL) at 24 months

4. HOMA-IR [at 24 months]

   insulin resistance marker HOMA-IR at 24 months

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• type 2 diabetes mellitus

• age>=18years

• no anti hyperglycemic agent for 3 months or low-dose oral hypoglycemic therapy

• metformin≤1g/day, acarbose≤300mg/day, voglibose≤0.9mg/day, nateglinide≤270mg/day, gliclazide≤80mg/day, glimepiride≤2mg/day, glibenclamide≤5mg/day (nateglinide or sulfonylurea <6months)

• 6.5% ≤ HbA1c ≤ 8.5%

• patients on no anti hyperglycemic agent for 3 months : HbA1c at screening

• patients on oral hypoglycemic therapy in 3months : HbA1c after wash-out

Exclusion Criteria:

• attending other clinical trials in 3months

• type I diabetes mellitus

• taking systemic steroid in 1month or requiring steroid therapy during clinical trial

• acute myocardial infarction in 6months

• alcoholics, pituitary or adrenal insufficiency, severe ketosis, diabetic ketoacidosis

• severe liver disease or AST, ALT ≥ 2.5 x ULN

• renal insufficiency (serum creatinine > 2.0mg/dl)

• other severe diabetic complication

• drug hypersensitivity history to nateglinide or sulfonylurea

• pregnant or plan to become pregnant during the clinical trial, lactation

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Myongji Hospital	Ilsan	Kyounggi	Korea, Republic of
2	Hanyang University Medical Center	Guri-si	Kyunggi-do	Korea, Republic of
3	Inha University Hospital	Incheon		Korea, Republic of
4	Hallym University Medical Center	Seoul		Korea, Republic of
5	Korea University Guro Hospital	Seoul		Korea, Republic of
6	Kyung hee University Medical Center	Seoul		Korea, Republic of
7	Ajou University Hospital	Suwon-si		Korea, Republic of

Sponsors and Collaborators

• Ajou University School of Medicine
• Korea University Guro Hospital
• Hanyang University
• Inha University Hospital
• Kyunghee University Medical Center
• Myongji Hospital
• Bundang CHA Hospital
• Wonju Severance Christian Hospital
• Hallym University Medical Center

Investigators

• Principal Investigator: Kwan Woo Lee, MD,PhD, Ajou University School of Medicine

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Kwan Woo Lee, Professor, Ajou University School of Medicine
• ClinicalTrials.gov Identifier: NCT00858013
• Other Study ID Numbers: AJIRB-CRO-08-197
• First Posted: Mar 9, 2009
• Last Update Posted: May 16, 2017
• Last Verified: May 1, 2017

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Kwan Woo Lee, Professor, Ajou University School of Medicine: Type 2 Diabetes Mellitus; Nateglinide; Pancreatic beta cell function
• Additional relevant MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2; Glimepiride; Nateglinide

Study Results

Participant Flow

Arm/Group Title	Nateglinide	Glimepiride
Arm/Group Description	Nateglinide 90~120mg three times a day Nateglinide: Nateglinide 90~120mg three times a day	Glimepiride 1~2mg once a day Glimepiride: Glimepiride 1~2mg once a day
Period Title: Overall Study
STARTED	46	42
COMPLETED	24	23
NOT COMPLETED	22	19

Baseline Characteristics

Arm/Group Title	Nateglinide	Glimepiride	Total
Arm/Group Description	Nateglinide 90~120mg three times a day Nateglinide: Nateglinide 90~120mg three times a day	Glimepiride 1~2mg once a day Glimepiride: Glimepiride 1~2mg once a day	Total of all reporting groups
Overall Participants	46	42	88
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	55.0 (10.5)	55.1 (12.3)	55 (11)
Sex: Female, Male (Count of Participants)
Female	23 50%	18 42.9%	41 46.6%
Male	23 50%	24 57.1%	47 53.4%

Outcome Measures

1. Primary Outcome

Title	The Durability of Nateglinide in Comparison With Those of Glimepiride Based on the Withdrawal Rate
Description	% monotherapy failure, that means % number of participants who withdrew from the study due to high HbA1c (>8.0%)
Time Frame	every 3 months following randomization, for 24 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Nateglinide	Glimepiride
Arm/Group Description	Nateglinide 90~120mg three times a day Nateglinide: Nateglinide 90~120mg three times a day	Glimepiride 1~2mg once a day Glimepiride: Glimepiride 1~2mg once a day
Measure Participants	24	23
Count of Participants [Participants]	10 21.7%	7 16.7%

2. Secondary Outcome

Title	HbA1c
Description	HbA1c (%) at 24 months
Time Frame	at 24 months

Outcome Measure Data

Analysis Population Description

data of participants who finished 24 months of follow-up

Arm/Group Title	Nateglinide	Glimepiride
Arm/Group Description	Nateglinide 90~120mg three times a day Nateglinide: Nateglinide 90~120mg three times a day	Glimepiride 1~2mg once a day Glimepiride: Glimepiride 1~2mg once a day
Measure Participants	14	16
Mean (Standard Deviation) [% HbA1c]	6.9 (0.6)	6.5 (0.5)

3. Secondary Outcome

Title	Fasting Glucose
Description	fasting glucose (mg/dL) at 24 months
Time Frame	at 24 months

Outcome Measure Data

Analysis Population Description

data of participants who finished 24 months of follow-up

Arm/Group Title	Nateglinide	Glimepiride
Arm/Group Description	Nateglinide 90~120mg three times a day Nateglinide: Nateglinide 90~120mg three times a day	Glimepiride 1~2mg once a day Glimepiride: Glimepiride 1~2mg once a day
Measure Participants	14	16
Mean (Standard Deviation) [mg/dL]	131.2 (25.9)	115.7 (19.8)

4. Secondary Outcome

Title	C-peptide
Description	c-peptide(uU/mL) at 24 months
Time Frame	at 24 months

Outcome Measure Data

Analysis Population Description

data of participants who finished 24 months of follow-up

Arm/Group Title	Nateglinide	Glimepiride
Arm/Group Description	Nateglinide 90~120mg three times a day Nateglinide: Nateglinide 90~120mg three times a day	Glimepiride 1~2mg once a day Glimepiride: Glimepiride 1~2mg once a day
Measure Participants	14	16
Mean (Standard Deviation) [uU/mL]	1.29 (0.41)	1.77 (0.72)

5. Secondary Outcome

Title	HOMA-IR
Description	insulin resistance marker HOMA-IR at 24 months
Time Frame	at 24 months

Outcome Measure Data

Analysis Population Description

data of participants who finished 24 months of follow-up

Arm/Group Title	Nateglinide	Glimepiride
Arm/Group Description	Nateglinide 90~120mg three times a day Nateglinide: Nateglinide 90~120mg three times a day	Glimepiride 1~2mg once a day Glimepiride: Glimepiride 1~2mg once a day
Measure Participants	14	16
Mean (Standard Deviation) [mg/dL x mIU/L]	2.40 (1.36)	2.31 (1.70)

Adverse Events

Time Frame	6 months
Arm/Group Title	Nateglinide		Glimepiride
Arm/Group Description	Nateglinide 90~120mg three times a day Nateglinide: Nateglinide 90~120mg three times a day		Glimepiride 1~2mg once a day Glimepiride: Glimepiride 1~2mg once a day
All Cause Mortality
	Nateglinide		Glimepiride
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/24 (0%)		0/23 (0%)
Serious Adverse Events
	Nateglinide		Glimepiride
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/24 (0%)		0/23 (0%)
Other (Not Including Serious) Adverse Events
	Nateglinide		Glimepiride
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/24 (25%)		1/23 (4.3%)
Endocrine disorders
hypoglycemia	1/24 (4.2%)		0/23 (0%)
Gastrointestinal disorders
dyspepsia	2/24 (8.3%)		0/23 (0%)
gall stone	1/24 (4.2%)		0/23 (0%)
gastritis	1/24 (4.2%)		0/23 (0%)
Nervous system disorders
dizziness	0/24 (0%)		1/23 (4.3%)
Skin and subcutaneous tissue disorders
herpes zoster	1/24 (4.2%)		0/23 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT 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.