- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01882907
Safety and Efficacy Study to Compare Vildagliptin to Pioglitazone as Adding on Metformin in Type 2 Diabetes
An Open-label, Randomized, Active-controlled Study to Compare the Effect of 16 Weeks Treatment With Vildagliptin to Pioglitazone as add-on Therapy to Metformin in Type 2 Diabetic Patients Inadequately Controlled With Metformin Monotherapy
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Type 2 diabetes mellitus (T2DM) is a chronic progressive disease characterized by hyperglycemia that result from pancreatic islet dysfunction. Presently available oral antihypoglycemic drug improves glycemic control over the short term, none has been shown to stop the progressive decline in beta cell function which contributes to the deterioration of glycemic control over time.
Pathophysiology of T2DM is known as tissue resistance for insulin and progressive beta cell failure. Which one attributes first is unclear, but non-obese T2DM patients often show normal fasting plasma glucose (FPG) but postprandial plasma glucose (PPG) level is high and reduced or lacking normal compensatory insulin secretion. In Korea, more than 80% of T2DM are non-obese type (BMI >= 27 ) and it was observed that basal insulin level and compensatory insulin secretion reaction were reduced in normal healthy population. Based on that, metformin is an established first line treatment for type 2 diabetes, acting primarily to enhance hepatic and peripheral insulin sensitivity. However, it has become increasingly apparent that many patients require a combination of agents to attain optimal glycemic control.
Better understanding of incretin effect on the pathophysiology of T2DM has recently led to development of new oral hypoglycemic agents. Vildagliptin is a potent and highly selective dipeptidyl peptidase (DPP)-IV inhibitor that improves islet function by increasing pancreatic alpha and beta cell responsiveness to glucose. Studies in patients with T2DM have shown that vildagliptin significantly reduced HbA1c and FPG level from baseline and did not induce weight gain and the incidence of hypoglycemia was low. In addition, studies in rodents support an effort of vildagliptin on beta cell remodeling.
The thiazolidinediones are effective in reducing HbA1C in obese T2DM patients and it is known that only thiazolidinedione can delay the beta cell failure . But recently, thiazolidinediones were found to be associated with a decrease in bone mineral density and to raise the risk of myocardial infarct and cardiovascular related mortality. Thus, there is a need for new classes of blood glucose lowering drug which has the potential to delay or prevent the progression of T2DM.
Study Type
Enrollment (Actual)
Phase
- Phase 4
Contacts and Locations
Study Locations
-
-
-
Busan, Korea, Republic of
- Kosin University Hospital
-
Busan, Korea, Republic of
- Pusan National University Hospital
-
Busan, Korea, Republic of
- Busan Saint Mary's Medical Center
-
Busan, Korea, Republic of
- Dong-AUniversity Medical Center
-
Busan, Korea, Republic of
- Inje University Baik Hospital
-
Changwon, Korea, Republic of
- Changwon Fatima Hospital
-
Daegu, Korea, Republic of
- Daegu Catholic University Medical Center
-
Daegu, Korea, Republic of
- Keimyung University Dongsan Medical Center
-
Daegu, Korea, Republic of
- Kyungbuk National Universtiy Hospital
-
Gwangju, Korea, Republic of
- Chonnam National University Hospital
-
Gwangju, Korea, Republic of
- Chosun University Hospital
-
Jeonju, Korea, Republic of
- Chonbuk National University Hospital
-
Jinju, Korea, Republic of
- Gyeongsang National University Hospital
-
Masan, Korea, Republic of
- Masan Samsung Medical Center
-
Ulsan, Korea, Republic of
- Ulsan University Hospital
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Age in the range of 18 to 80 years
- HbA1c 7 to 11%
- FPG < 270 mg/dL (15 mmol/L);
- Agreement to maintain prior diet & exercise
- Written informed consent to participate in the study
Exclusion criteria:
- Type 1 diabetes or Any kind of secondary diabetes
- Pregnant or lactating women
- Acute infections which may affect blood glucose control within 4 weeks prior to visit 1.
- Significant diabetes complications e.g., symptomatic autonomic neuropathy or gastroparesis
Previous history of severe cardiovascular disease such as
- Torsades de Pointes, sustained and clinically relevant ventricular tachycardia, or ventricular fibrillation
- Percutaneous coronary intervention within the past 3 months
Any of the following within the past 6 months
- Myocardial infarction (MI) (if the visit 1 ECG reveals patterns consistent with an MI and the date of the event cannot be determined, then the patient can enter the study at the discretion of the investigator and the sponsor)
- Coronary artery bypass surgery
- Unstable angina
- Stroke
- Congestive heart failure (NYHA class I to IV)
- Liver disease such as cirrhosis or chronic active hepatitis
- Known sensitivity to pioglitazone, rosiglitazone, or similar drugs
- Chronic insulin treatment (> 4 weeks of treatment in the absence of an intercurrent illness) within the past 6 months
- Chronic oral or parenteral corticosteroid treatment (> 7 consecutive days of treatment) within 8 weeks prior to visit 1
Any of the following laboratory abnormalities
- Alanine aminotransferase (ALT), aspartate aminotransferase (AST) greater than 2.5 times the upper limit of the normal range at visit 1
- Direct bilirubin greater than 1.3 times the upper limit of the normal range at visit 1
- Serum creatinine levels > 2.5 mg/dL (220 μmol/L) at visit 1
- Clinically significant thyroid-stimulating hormone (TSH) outside normal range at visit 1
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: vildagliptin
vildagliptin add-on the therapy to metformin in patients with type 2 diabetes inadequately controlled with metformin monotherapy
|
vildagliptin 50mg bid for 16 weeks
Other Names:
|
Active Comparator: pioglitazone
Pioglitazone add-on the therapy to metformin in patients with type 2 diabetes inadequately controlled with metformin monotherapy
|
Pioglitazone 15mg bid for 16 weeks
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Non-inferiority of HbA1C Change From Baseline in Vildagliptin + Metformin Group Compared With Pioglitazone + Metformin Group
Time Frame: 16 weeks
|
16 weeks
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
the Mean Changes of FPG and PPG From Baseline Between Vildagliptin + Metformin and Pioglitazone + Metformin Groups
Time Frame: 16 weeks , visit 5
|
|
16 weeks , visit 5
|
the Mean Changes of Lipid Profiles From Baseline Between Vildagliptin + Metformin and Pioglitazone + Metformin Groups
Time Frame: 16 weeks, visit 5
|
The Mean Changes of Lipid Profiles(Triglyceride, Total cholesterol, LDL, HDL, Non-HDL cholesterol) From Baseline Between Vildagliptin + Metformin and Pioglitazone + Metformin Groups after 16weeks
|
16 weeks, visit 5
|
the Mean Changes of Body Weight From Baseline Between Vildagliptin + Metformin and Pioglitazone + Metformin Groups
Time Frame: 16 weeks, visit 5
|
16 weeks, visit 5
|
|
the Mean Changes of Insulin, C-peptide, HOMA-IR, HOMA-beta From Baseline Between Vildagliptin + Metformin and Pioglitazone + Metformin Groups
Time Frame: 16 weeks, visit 5
|
16 weeks, visit 5
|
Other Outcome Measures
Outcome Measure |
Time Frame |
---|---|
the Numbers of Participants With Adverse Events Between Vildagliptin + Metformin and Pioglitazone + Metformin Groups
Time Frame: 16 weeks, visit 3,4,5
|
16 weeks, visit 3,4,5
|
Collaborators and Investigators
Investigators
- Principal Investigator: In Ju Kim, MD, Pusan National University Hospital
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Glucose Metabolism Disorders
- Metabolic Diseases
- Endocrine System Diseases
- Diabetes Mellitus
- Diabetes Mellitus, Type 2
- Hypoglycemic Agents
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Protease Inhibitors
- Dipeptidyl-Peptidase IV Inhibitors
- Pioglitazone
- Vildagliptin
Other Study ID Numbers
- CLAF237AKR05T
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Type 2 Diabetes
-
Antonio Di MauroCompletedType-2 DiabetesItaly
-
DiaMedica Therapeutics IncCompletedDiabetes Type 2Netherlands
-
RenJi HospitalUnknownType 2 Diabetes.China
-
Chengdu Brilliant Pharmaceutical Co., Ltd.Not yet recruitingType 2 Diabetes Mellitus
-
Nanjing First Hospital, Nanjing Medical UniversityRecruitingType 2 Diabetes MellitusChina
-
Xiangya Hospital of Central South UniversityRecruitingType 2 Diabetes MellitusChina
-
University of Alabama at BirminghamCompletedType 2 Diabetes MellitusUnited States
-
Imperial College LondonAstraZeneca; Huma; North West London Collaboration of CCGs (NWL CCGs); Imperial...CompletedType 2 Diabetes MellitusUnited Kingdom
-
Universiti Sains MalaysiaCompleted
-
University of Alabama at BirminghamUnited States Department of Defense; Loma Linda University; Brenda Davis Nutrition... and other collaboratorsCompletedType 2 Diabetes Mellitus
Clinical Trials on vildagliptin
-
Laboratorios Silanes S.A. de C.V.Recruiting
-
Novartis PharmaceuticalsCompletedType II Diabetes Mellitus | Congestive Heart FailureRussian Federation, Singapore, Italy, Czechia, Lithuania, Germany, Guatemala, India, Denmark, Estonia, Slovakia, Romania, Latvia, Greece, Poland
-
Novartis PharmaceuticalsCompletedType 2 Diabetes MellitusSpain, Poland, South Africa, Taiwan, Hong Kong, Norway, Italy, Bulgaria, Latvia, Lithuania, Germany, Turkey, Argentina, Israel, Korea, Republic of, Dominican Republic, Guatemala, Brazil, Colombia, Peru, Philippines, Russian Federation and more
-
Novartis PharmaceuticalsCompletedDiabetes Mellitus, Type 2Switzerland, Germany
-
NovartisCompleted
-
Novartis PharmaceuticalsCompletedDiabetes Mellitus, Type 2United States, Germany
-
Bio-innova Co., LtdNot yet recruiting
-
Radboud University Medical CenterCompletedType 2 Diabetes | Endothelial DysfunctionNetherlands
-
Novartis PharmaceuticalsCompletedDiabetes Mellitus, Type 2United States
-
NovartisCompletedDiabetes Mellitus, Type 2Germany, United States