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

• Sponsor: Novartis Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01766778
• Collaborator: (none)
• Enrollment: 117
• Locations: 3
• Arms: 2
• Actual Duration (Months): 29.3
• Patients Per Site: 39
• Patients Per Site Per Month: 1.3

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Type-2 Diabetes Mellitus	Drug: LAF237 (vildagliptin); Drug: Metformin	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 117 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Local Phase IV, Multicenter, Open-label Study to Evaluate Early add-on Vildagliptin in Patients With Type 2 Diabetes Inadequately Controlled by Metformin
• Actual Study Start Date: May 13, 2013
• Actual Primary Completion Date: Oct 22, 2015
• Actual Study Completion Date: Oct 22, 2015

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Change of Glycosylated Hemoglobin A1c (HbA1c) From Baseline to Month 12 [Baseline, Month 12 (weeK 52)]

   HbA1c is an integrated measure of average glucose concentration in plasma in the last 2-3 months. Blood samples were collected to analyze HbA1c

Secondary Outcome Measures

1. Change of Glycosylated Hemoglobin A1c (HbA1c) From Baseline to Month 3, 6, 9 and 12 (Based on MMRM Analysis) [Baseline, Month 3, 6, 9 and 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. 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.

2. Change in Fasting Plasma Glucose (FPG) From Baseline to Month 3, 6, 9 and 12 (Based on MMRM Analysis) [Baseline, Month 3, 6, 9 and 12]

   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.

3. Percentage of Patients Achieving Good Glycemic Control [Month 3, 6, 9, 12]

   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.

4. Percentage of Overall Drug Compliance in 12 Months [Month 12]

   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))]

5. Number of Patients With Adverse Events, Serious Adverse Events and Death as an Assessment of Overall Safety and Tolerability [Month 12]

   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.

Eligibility Criteria

Criteria

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

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novartis Investigative Site	Hong Kong SAR		Hong Kong
2	Novartis Investigative Site	HongKong		Hong Kong
3	Novartis Investigative Site	Tuen Mun		Hong Kong

Sponsors and Collaborators

• Novartis Pharmaceuticals

Investigators

• Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT01766778
• Other Study ID Numbers: CLAF237AHK01
• First Posted: Jan 11, 2013
• Last Update Posted: May 15, 2017
• Last Verified: Apr 1, 2017

• Keywords provided by Novartis Pharmaceuticals: type-2 diabetes mellitus, inadequately controlled Metformin
• Additional relevant MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2; Metformin; Vildagliptin

Study Results

Participant Flow

Pre-assignment Detail	There was 117 patients randomized and received either Vildagliptin 50mg QD or 50 mg BID.

Arm/Group Title	LAF237 (Vildagliptin) 50mg Once Daily (QD)	LAF237 (Vildagliptin) 50mg Twice Daily (BID)
Arm/Group Description	Vildagliptin 50mg QD plus stabilized or maximum tolerated dose of Metformin	Vildagliptin 50mg BID plus stabilized or maximum tolerated dose of Metformin
Period Title: Overall Study
STARTED	56	61
COMPLETED	51	57
NOT COMPLETED	5	4

Baseline Characteristics

Arm/Group Title	LAF237 (Vildagliptin) 50mg Once Daily (QD)	LAF237 (Vildagliptin) 50mg Twice Daily (BID)	Total
Arm/Group Description	Vildagliptin 50mg QD plus stabilized or maximum tolerated dose of Metformin	Vildagliptin 50mg BID plus stabilized or maximum tolerated dose of Metformin	Total of all reporting groups
Overall Participants	56	61	117
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	58 (10.3)	59 (10.0)	58 (10.1)
Sex: Female, Male (Count of Participants)
Female	26 46.4%	31 50.8%	57 48.7%
Male	30 53.6%	30 49.2%	60 51.3%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

Intent to treat (ITT) analysis set included all randomized patients who received at least one dose of study medication. Patients with both baseline and 12 month data were included in this analysis

Arm/Group Title	LAF237 (Vildagliptin) 50mg Once Daily (QD)	LAF237 (Vildagliptin) 50mg Twice Daily (BID)
Arm/Group Description	Vildagliptin 50mg QD plus stabilized or maximum tolerated dose of Metformin	Vildagliptin 50mg BID plus stabilized or maximum tolerated dose of Metformin
Measure Participants	49	50
Mean (Standard Deviation) [percentage of Glycosylated Hemoglobin]	-0.8 (1.01)	-1.0 (1.24)

2. Secondary Outcome

Title	Change of Glycosylated Hemoglobin A1c (HbA1c) From Baseline to Month 3, 6, 9 and 12 (Based on MMRM Analysis)
Description	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.
Time Frame	Baseline, Month 3, 6, 9 and 12

Outcome Measure Data

Analysis Population Description

Intent to treat (ITT) analysis set included all randomized patients who received at least one dose of study medication. .

Arm/Group Title	LAF237 (Vildagliptin) 50mg Once Daily (QD)	LAF237 (Vildagliptin) 50mg Twice Daily (BID)
Arm/Group Description	Vildagliptin 50mg QD plus stabilized or maximum tolerated dose of Metformin	Vildagliptin 50mg BID plus stabilized or maximum tolerated dose of Metformin
Measure Participants	56	61
3 month from baseline	-0.6 (0.11)	-0.9 (0.10)
6 month from baseline	-0.7 (0.13)	-0.9 (0.12)
9 month from baseline	-0.7 (0.13)	-0.7 (0.13)
12 month from baseline	-0.6 (0.15)	-0.6 (0.15)

3. Secondary Outcome

Title	Change in Fasting Plasma Glucose (FPG) From Baseline to Month 3, 6, 9 and 12 (Based on MMRM Analysis)
Description	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.
Time Frame	Baseline, Month 3, 6, 9 and 12

Outcome Measure Data

Analysis Population Description

Intent to treat (ITT) analysis set included all randomized patients who received at least one dose of study medication.

Arm/Group Title	LAF237 (Vildagliptin) 50mg Once Daily (QD)	LAF237 (Vildagliptin) 50mg Twice Daily (BID)
Arm/Group Description	Vildagliptin 50mg QD plus stabilized or maximum tolerated dose of Metformin	Vildagliptin 50mg BID plus stabilized or maximum tolerated dose of Metformin
Measure Participants	56	61
3 month from baseline	-0.9 (0.18)	-1.3 (0.16)
6 month from baseline	-1.2 (0.18)	-0.9 (0.17)
9 month from baseline	-1.1 (0.17)	-1.0 (0.16)
12 month from baseline	-0.9 (0.20)	-0.8 (0.20)

4. Secondary Outcome

Title	Percentage of Patients Achieving Good Glycemic Control
Description	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.
Time Frame	Month 3, 6, 9, 12

Outcome Measure Data

Analysis Population Description

Intent to treat (ITT) analysis set included all randomized patients who received at least one dose of study medication. 'n' indicates patients with HbA1c data in that time point.

Arm/Group Title	LAF237 (Vildagliptin) 50mg Once Daily (QD)	LAF237 (Vildagliptin) 50mg Twice Daily (BID)
Arm/Group Description	Vildagliptin 50mg QD plus stabilized or maximum tolerated dose of Metformin	Vildagliptin 50mg BID plus stabilized or maximum tolerated dose of Metformin
Measure Participants	56	61
At Month 3	33.3	47.5
At Month 6	39.2	45.6
At Month 9	45.1	47.4
At Month 12	49.0	40.0

5. Secondary Outcome

Title	Percentage of Overall Drug Compliance in 12 Months
Description	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))]
Time Frame	Month 12

Outcome Measure Data

Analysis Population Description

Intent to treat (ITT) analysis set included all randomized patients who received at least one dose of study medication. Patients who had reported dosing compliance were included in this analysis.

Arm/Group Title	LAF237 (Vildagliptin) 50mg Once Daily (QD)	LAF237 (Vildagliptin) 50mg Twice Daily (BID)
Arm/Group Description	Vildagliptin 50mg QD plus stabilized or maximum tolerated dose of Metformin	Vildagliptin 50mg BID plus stabilized or maximum tolerated dose of Metformin
Measure Participants	21	21
Mean (Standard Deviation) [Percentage of overall drug compliance]	96.90 (5.682)	97.48 (6.277)

6. Secondary Outcome

Title	Number of Patients With Adverse Events, Serious Adverse Events and Death as an Assessment of Overall Safety and Tolerability
Description	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.
Time Frame	Month 12

Outcome Measure Data

Analysis Population Description

Intent to treat (ITT) analysis set included all randomized patients who received at least one dose of study medication.

Arm/Group Title	LAF237 (Vildagliptin) 50mg Once Daily (QD)	LAF237 (Vildagliptin) 50mg Twice Daily (BID)
Arm/Group Description	Vildagliptin 50mg QD plus stabilized or maximum tolerated dose of Metformin	Vildagliptin 50mg BID plus stabilized or maximum tolerated dose of Metformin
Measure Participants	56	61
Any adverse events	15	14
Serious adverse events	2	2
Death	0	0
Patients discontinued due to any AE/SAE	4	4

Adverse Events

Arm/Group Title	LAF237 (Vildagliptin) 50mg Once Daily (QD)		LAF237 (Vildagliptin) 50mg Twice Daily (BID)
Arm/Group Description	Vildagliptin 50mg QD plus stabilized or maximum tolerated dose of Metformin		Vildagliptin 50mg BID plus stabilized or maximum tolerated dose of Metformin
All Cause Mortality
	LAF237 (Vildagliptin) 50mg Once Daily (QD)		LAF237 (Vildagliptin) 50mg Twice Daily (BID)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	LAF237 (Vildagliptin) 50mg Once Daily (QD)		LAF237 (Vildagliptin) 50mg Twice Daily (BID)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/56 (3.6%)		2/61 (3.3%)
Gastrointestinal disorders
Duodenitis	1/56 (1.8%)		0/61 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Leukemia	0/56 (0%)		1/61 (1.6%)
Renal and urinary disorders
Renal failure	0/56 (0%)		1/61 (1.6%)
stone impairation over proximal urethra	1/56 (1.8%)		0/61 (0%)
Other (Not Including Serious) Adverse Events
	LAF237 (Vildagliptin) 50mg Once Daily (QD)		LAF237 (Vildagliptin) 50mg Twice Daily (BID)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	14/56 (25%)		7/61 (11.5%)
Infections and infestations
Tinea	0/56 (0%)		2/61 (3.3%)
Upper Respiratory Tract Infection	8/56 (14.3%)		2/61 (3.3%)
Investigations
Elevated liver function test	2/56 (3.6%)		2/61 (3.3%)
Metabolism and nutrition disorders
Hyperkalemia	1/56 (1.8%)		2/61 (3.3%)
Hypokalemia	2/56 (3.6%)		0/61 (0%)
Nervous system disorders
Dizziness	2/56 (3.6%)		1/61 (1.6%)
Respiratory, thoracic and mediastinal disorders
Cough	2/56 (3.6%)		2/61 (3.3%)
Skin and subcutaneous tissue disorders
Eczema	2/56 (3.6%)		1/61 (1.6%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

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 or disclosure of trial results in their entirety.