Early add-on Vildagliptin in Patients With Type 2 Diabetes Inadequately Controlled by Metformin

A Local Phase IV, Multicenter, Open-label Study to Evaluate Early add-on Vildagliptin in Patients With Type 2 Diabetes Inadequately Controlled by Metformin

The purpose of this study was to observe change of HbA1c over time from baseline to month 12. The ultimate goal of this study was to provide a local reference value to the physicians & patients in the future when they consider initiating Vildagliptin and taking balance between efficacy, compliance, risk factors, convenience and medication cost.

Study Overview

• Status: Completed
• Conditions: Type-2 Diabetes Mellitus
• Intervention / Treatment: Drug: LAF237 (vildagliptin); Drug: Metformin

• Study Type: Interventional
• Enrollment (Actual): 117
• Phase: Phase 4

Contacts and Locations

Study Locations

• Hong Kong
  • Hong Kong SAR, Hong Kong
    • Novartis Investigative Site
  • HongKong, Hong Kong
    • Novartis Investigative Site
  • Tuen Mun, Hong Kong
    • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Male or Female in age ≥18 at Visit 1
2. Type 2 diabetes mellitus (T2DM) patients on their maximum tolerated dose of Metformin for more than 3 months
3. HbA1c (glycosylated hemoglobin) at Visit 1 greater than 7.0%
4. With nearest documented record of HbA1c before Visit 1 greater than 7.0% after patient reached his/her maximum tolerated dose of Metformin

Key Exclusion Criteria:

1. Patients with hepatic impairment, including patients with a pre-treatment alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 2.5 X the upper limit of normal at Visit 1
2. Patients with moderate or severe renal impairment or end-stage-renal-disease (ESRD) on haemodialysis at the time of enrolment
3. Patients with hereditary problems of galactose intolerance, the Lapp lactose deficiency or glucose-galactose malabsorption
4. Pregnant women or breastfeeding women at the time of enrolment
5. Use of insulin or other oral anti-diabetic drug (OAD) apart from Metformin in the past for T2DM treatment

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: LAF237 (vildagliptin) 50mg once daily (QD); Vildagliptin 50mg QD plus stabilized or maximum tolerated dose of Metformin	Drug: LAF237 (vildagliptin); Vildagliptin 50mg capsule; Other Names: LAF237; Drug: Metformin; Metformin maximum tolerance dose
Active Comparator: LAF237 (vildagliptin) 50mg twice daily (BID); Vildagliptin 50mg BID plus stabilized or maximum tolerated dose of Metformin	Drug: LAF237 (vildagliptin); Vildagliptin 50mg capsule; Other Names: LAF237; Drug: Metformin; Metformin maximum tolerance dose

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change of Glycosylated Hemoglobin A1c (HbA1c) From Baseline to Month 12	HbA1c is an integrated measure of average glucose concentration in plasma in the last 2-3 months. Blood samples were collected to analyze HbA1c	Baseline, Month 12 (weeK 52)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change of Glycosylated Hemoglobin A1c (HbA1c) From Baseline to Month 3, 6, 9 and 12 (Based on MMRM Analysis)	HbA1c is an integrated measure of average glucose concentration in plasma in the last 2-3 months. Blood samples were collected to analyze HbA1c. Mixed Model of Repeated Measures (MMRM) was used to analyze this outcome. For the MMRM analysis, the model includes terms for treatment, period, treatment-by-period interaction and baseline value, and further adjusted by age, pre-existing hypertension and microvascular and macrovascular complications for diabetes mellitus. The variables selected for baseline adjustment were based on the lowest AIC.	Baseline, Month 3, 6, 9 and 12
Change in Fasting Plasma Glucose (FPG) From Baseline to Month 3, 6, 9 and 12 (Based on MMRM Analysis)	Blood samples were collected to analyze fasting plasma glucose. Mixed Model of Repeated Measures (MMRM) was used to analyze this outcome. For the MMRM analysis, the model included terms for treatment, period, treatment-by-period interaction and baseline value, and further adjusted by pre-existing hypertension. The variable selected for baseline adjustment was based on the lowest AIC.	Baseline, Month 3, 6, 9 and 12
Percentage of Patients Achieving Good Glycemic Control	Blood samples were collected to analyze HbA1c. Good glycemic control is defined as patient achieving Hb1Ac < 7.0%. Percentage of patients who achieved HbA1c less than 7.0% at month 3, 6, 9 and 12 were reported for this endpoint.	Month 3, 6, 9, 12
Percentage of Overall Drug Compliance in 12 Months	The overall drug compliance (%) = (Observed Consumption / Expected Consumption) x 100% Where (Observed Consumption / Expected Consumption) = [1- (Number of missing tablets from all visits/(sum of Allocated Daily Dosage (in tablets) from all visits × No. of Days between the Date Dispensed and the Date Returned))]	Month 12
Number of Patients With Adverse Events, Serious Adverse Events and Death as an Assessment of Overall Safety and Tolerability	This analysis reported percentage patients with adverse events and patient discontinued from the study due to adverse events. Aslo, percentage of patients with serious adverse events and death was reported.	Month 12

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): May 13, 2013
• Primary Completion (Actual): October 22, 2015
• Study Completion (Actual): October 22, 2015

Study Registration Dates

• First Submitted: January 9, 2013
• First Submitted That Met QC Criteria: January 9, 2013
• First Posted (Estimate): January 11, 2013

Study Record Updates

• Last Update Posted (Actual): May 15, 2017
• Last Update Submitted That Met QC Criteria: April 7, 2017
• Last Verified: April 1, 2017

More Information

Terms related to this study

• Keywords: type-2 diabetes mellitus, inadequately controlled Metformin
• 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; Metformin; Vildagliptin
• Other Study ID Numbers: CLAF237AHK01