Trial Outcomes & Findings for Study of Efficacy and Safety of Vildagliptin as add-on Insulin Therapy in T2DM Patients (NCT NCT02002221)

NCT ID: NCT02002221

Last Updated: 2016-03-01

Results Overview

HbA1c was performed on a blood sample obtained and measured by high performance liquid chromatography performed at a central laboratory.

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 156 participants
• Primary outcome timeframe: Baseline, week 12
• Results posted on: 2016-03-01

Participant Flow

Participant milestones

Measure	Vildagliptin (LAF237) Patients received vildagliptin (LAF237) 50 mg tablets twice daily for 12 weeks. Patients continued on a stable dose of long-acting or intermediate-acting or pre-mixed insulin, and metformin if applicable, throughout the study	Placebo In this arm, patients received vildagliptin 50 mg matching placebo tablets twice daily for 12 weeks. Patients continued on a stable dose of long-acting or intermediate-acting or pre-mixed insulin, and metformin if applicable, throughout the study
Overall Study STARTED	78	78
Overall Study COMPLETED	76	75
Overall Study NOT COMPLETED	2	3

Reasons for withdrawal

Measure	Vildagliptin (LAF237) Patients received vildagliptin (LAF237) 50 mg tablets twice daily for 12 weeks. Patients continued on a stable dose of long-acting or intermediate-acting or pre-mixed insulin, and metformin if applicable, throughout the study	Placebo In this arm, patients received vildagliptin 50 mg matching placebo tablets twice daily for 12 weeks. Patients continued on a stable dose of long-acting or intermediate-acting or pre-mixed insulin, and metformin if applicable, throughout the study
Overall Study Adverse Event	2	1
Overall Study Unsatisfactory therapeutic effect	0	1
Overall Study Patient withdrew consent	0	1

Baseline Characteristics

Study of Efficacy and Safety of Vildagliptin as add-on Insulin Therapy in T2DM Patients

Baseline characteristics by cohort

Measure	Vildagliptin (LAF237) n=78 Participants Patients received vildagliptin (LAF237) 50 mg tablets twice daily for 12 weeks. Patients continued on a stable dose of long-acting or intermediate-acting or pre-mixed insulin, and metformin if applicable, throughout the study	Placebo n=78 Participants In this arm, patients received vildagliptin 50 mg matching placebo tablets twice daily for 12 weeks. Patients continued on a stable dose of long-acting or intermediate-acting or pre-mixed insulin, and metformin if applicable, throughout the study	Total n=156 Participants Total of all reporting groups
Age, Continuous	58.5 Years STANDARD_DEVIATION 9.57 • n=5 Participants	60.1 Years STANDARD_DEVIATION 9.11 • n=7 Participants	59.3 Years STANDARD_DEVIATION 9.34 • n=5 Participants
Sex: Female, Male Female	23 Participants n=5 Participants	22 Participants n=7 Participants	45 Participants n=5 Participants
Sex: Female, Male Male	55 Participants n=5 Participants	56 Participants n=7 Participants	111 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline, week 12

Population: The full analysis set consisted of all randomized patients who received at least one dose of study medication and had at least one post-baseline assessment of efficacy parameter measurement.

HbA1c was performed on a blood sample obtained and measured by high performance liquid chromatography performed at a central laboratory.

Outcome measures

Measure	Vildagliptin (LAF237) n=78 Participants Patients received vildagliptin (LAF237) 50 mg tablets twice daily for 12 weeks. Patients continued on a stable dose of long-acting or intermediate-acting or pre-mixed insulin, and metformin if applicable, throughout the study	Placebo n=78 Participants In this arm, patients received vildagliptin 50 mg matching placebo tablets twice daily for 12 weeks. Patients continued on a stable dose of long-acting or intermediate-acting or pre-mixed insulin, and metformin if applicable, throughout the study
Change From Baseline in Glycosylated Hemoglobin (HbA1c) at 12 Weeks Between Treatment Groups	-1.01 percentage of glycosylated haemoglobin Standard Error 0.06	-0.11 percentage of glycosylated haemoglobin Standard Error 0.06

SECONDARY outcome

Timeframe: Baseline, week 12

Population: The full analysis set consisted of all randomized patients who received at least one dose of study medication and had at least one post-baseline assessment of efficacy parameter measurement.

Responder rate was analyzed in categories: Criterion 1- Endpoint HbA1c ≤ 6.5%, Criterion 2- Endpoint HbA1c < 7% , Criterion 3- Endpoint HbA1c < 7% in patients with baseline HbA1c ≤ 8%, Criterion 4- HbA1c reduction from baseline at endpoint ≥ 1%, Criterion 5- HbA1c reduction from baseline at endpoint ≥ 0.5%. The number of patients analyzed for Criterion 1 and 2 include only patients with baseline HbA1c ≥ 7% (> 6.5%) and endpoint HbA1c measurement. The number of patients analyzed for Criterion 3 includes only patients with 7% ≤ baseline HbA1c ≤ 8% and endpoint HbA1c measurement. The number of patients analyzed for Criterion 4 and 5 include patients with both baseline and endpoint HbA1c measurements.

Outcome measures

Measure	Vildagliptin (LAF237) n=78 Participants Patients received vildagliptin (LAF237) 50 mg tablets twice daily for 12 weeks. Patients continued on a stable dose of long-acting or intermediate-acting or pre-mixed insulin, and metformin if applicable, throughout the study	Placebo n=78 Participants In this arm, patients received vildagliptin 50 mg matching placebo tablets twice daily for 12 weeks. Patients continued on a stable dose of long-acting or intermediate-acting or pre-mixed insulin, and metformin if applicable, throughout the study
Percentage of Patients Meeting Responder Rates in HbA1c At least one criterion met (n = 78, 78)	67 percentage of patients	21 percentage of patients
Percentage of Patients Meeting Responder Rates in HbA1c Criterion 1 (n= 77, 78)	23 percentage of patients	2 percentage of patients
Percentage of Patients Meeting Responder Rates in HbA1c Criterion 2 (n= 76, 77)	38 percentage of patients	3 percentage of patients
Percentage of Patients Meeting Responder Rates in HbA1c Criterion 3 (n= 42, 37)	33 percentage of patients	3 percentage of patients
Percentage of Patients Meeting Responder Rates in HbA1c Criterion 4 (n=78, 78)	38 percentage of patients	5 percentage of patients
Percentage of Patients Meeting Responder Rates in HbA1c Criterion 5 (n= 78, 78)	62 percentage of patients	20 percentage of patients

SECONDARY outcome

Timeframe: Baseline, week 12

Population: The full analysis set consisted of all randomized patients who received at least one dose of study medication and had at least one post-baseline assessment of efficacy parameter measurement. Number of patients with observations at both baseline and endpoint are analyzed in this endpoint.

FPG was performed on a blood sample obtained and analyzed at a central laboratory.

Outcome measures

Measure	Vildagliptin (LAF237) n=78 Participants Patients received vildagliptin (LAF237) 50 mg tablets twice daily for 12 weeks. Patients continued on a stable dose of long-acting or intermediate-acting or pre-mixed insulin, and metformin if applicable, throughout the study	Placebo n=78 Participants In this arm, patients received vildagliptin 50 mg matching placebo tablets twice daily for 12 weeks. Patients continued on a stable dose of long-acting or intermediate-acting or pre-mixed insulin, and metformin if applicable, throughout the study
Change From Baseline in Fasting Plasma Glucose (FPG) at 12 Weeks	-21.87 mg/dL Standard Error 4.05	-0.30 mg/dL Standard Error 4.04

SECONDARY outcome

Timeframe: 12 weeks

Population: The safety set consisted of all patients who received at least one dose of study medication.

Hypoglycemic events are defined as a) symptoms suggestive of hypoglycemia, where the patient is able to initiate self-treatment and plasma glucose measurement is < 56 mg/dL (grade 1), b) symptoms suggestive of hypoglycemia, where the patient is unable to initiate self-treatment and plasma glucose measurement is < 56 mg/dL (grade 2), c) symptoms suggestive of hypoglycemia, where the patient is unable to initiate self-treatment and no plasma glucose measurement is available (suspected grade 2)

Outcome measures

Measure	Vildagliptin (LAF237) n=78 Participants Patients received vildagliptin (LAF237) 50 mg tablets twice daily for 12 weeks. Patients continued on a stable dose of long-acting or intermediate-acting or pre-mixed insulin, and metformin if applicable, throughout the study	Placebo n=78 Participants In this arm, patients received vildagliptin 50 mg matching placebo tablets twice daily for 12 weeks. Patients continued on a stable dose of long-acting or intermediate-acting or pre-mixed insulin, and metformin if applicable, throughout the study
Number of Participants With Incidence of Hypoglycemia and Severe Hypoglycemia at least one hypoglycemic event	5 Participants	1 Participants
Number of Participants With Incidence of Hypoglycemia and Severe Hypoglycemia grade 2 hypoglycemic events	0 Participants	0 Participants
Number of Participants With Incidence of Hypoglycemia and Severe Hypoglycemia suspected grade 2 hypoglycemic events	0 Participants	0 Participants

SECONDARY outcome

Timeframe: 12 weeks

Population: The safety set consisted of all patients who received at least one dose of study medication.

The occurrence of adverse events was sought by non-directive questioning of the patient at each visit. Adverse events are defined as appearance or worsening of any undesirable symptom, vital sign, or medical conditions. Serious adverse events are any untoward medical occurrences that result in death, are life threatening, require (or prolong) hospitalization, cause persistent or significant disability/incapacity, result in congenital anomalies or birth defects, or are other conditions which in judgment of investigators represent significant hazards.

Outcome measures

Measure	Vildagliptin (LAF237) n=78 Participants Patients received vildagliptin (LAF237) 50 mg tablets twice daily for 12 weeks. Patients continued on a stable dose of long-acting or intermediate-acting or pre-mixed insulin, and metformin if applicable, throughout the study	Placebo n=78 Participants In this arm, patients received vildagliptin 50 mg matching placebo tablets twice daily for 12 weeks. Patients continued on a stable dose of long-acting or intermediate-acting or pre-mixed insulin, and metformin if applicable, throughout the study
Number of Participants With Adverse Events, Serious Adverse Events and Death Any adverse events	36 Participants	34 Participants
Number of Participants With Adverse Events, Serious Adverse Events and Death Serious adverse events	2 Participants	1 Participants
Number of Participants With Adverse Events, Serious Adverse Events and Death Death	0 Participants	0 Participants

Adverse Events

Vildagliptin (LAF237)

Serious events: 2 serious events

Other events: 22 other events

Deaths: 0 deaths

Placebo

Serious events: 1 serious events

Other events: 21 other events

Deaths: 0 deaths

Serious adverse events

Measure	Vildagliptin (LAF237) n=78 participants at risk Patients received vildagliptin (LAF237) 50 mg tablets twice daily for 12 weeks. Patients continued on a stable dose of long-acting or intermediate-acting or pre-mixed insulin, and metformin if applicable, throughout the study	Placebo n=78 participants at risk In this arm, patients received vildagliptin 50 mg matching placebo tablets twice daily for 12 weeks. Patients continued on a stable dose of long-acting or intermediate-acting or pre-mixed insulin, and metformin if applicable, throughout the study
Cardiac disorders Angina pectoris	0.00% 0/78 The safety set consisted of all patients who received at least one dose of study medication. Patients were analyzed according to the treatment received.	1.3% 1/78 The safety set consisted of all patients who received at least one dose of study medication. Patients were analyzed according to the treatment received.
Injury, poisoning and procedural complications Femoral neck fracture	1.3% 1/78 The safety set consisted of all patients who received at least one dose of study medication. Patients were analyzed according to the treatment received.	0.00% 0/78 The safety set consisted of all patients who received at least one dose of study medication. Patients were analyzed according to the treatment received.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Squamous cell carcinoma of the tongue	1.3% 1/78 The safety set consisted of all patients who received at least one dose of study medication. Patients were analyzed according to the treatment received.	0.00% 0/78 The safety set consisted of all patients who received at least one dose of study medication. Patients were analyzed according to the treatment received.

Other adverse events

Measure	Vildagliptin (LAF237) n=78 participants at risk Patients received vildagliptin (LAF237) 50 mg tablets twice daily for 12 weeks. Patients continued on a stable dose of long-acting or intermediate-acting or pre-mixed insulin, and metformin if applicable, throughout the study	Placebo n=78 participants at risk In this arm, patients received vildagliptin 50 mg matching placebo tablets twice daily for 12 weeks. Patients continued on a stable dose of long-acting or intermediate-acting or pre-mixed insulin, and metformin if applicable, throughout the study
General disorders Asthenia	7.7% 6/78 The safety set consisted of all patients who received at least one dose of study medication. Patients were analyzed according to the treatment received.	7.7% 6/78 The safety set consisted of all patients who received at least one dose of study medication. Patients were analyzed according to the treatment received.
General disorders Hunger	9.0% 7/78 The safety set consisted of all patients who received at least one dose of study medication. Patients were analyzed according to the treatment received.	3.8% 3/78 The safety set consisted of all patients who received at least one dose of study medication. Patients were analyzed according to the treatment received.
Infections and infestations Nasopharyngitis	12.8% 10/78 The safety set consisted of all patients who received at least one dose of study medication. Patients were analyzed according to the treatment received.	14.1% 11/78 The safety set consisted of all patients who received at least one dose of study medication. Patients were analyzed according to the treatment received.
Metabolism and nutrition disorders Hypoglycaemia	6.4% 5/78 The safety set consisted of all patients who received at least one dose of study medication. Patients were analyzed according to the treatment received.	1.3% 1/78 The safety set consisted of all patients who received at least one dose of study medication. Patients were analyzed according to the treatment received.
Nervous system disorders Tremor	9.0% 7/78 The safety set consisted of all patients who received at least one dose of study medication. Patients were analyzed according to the treatment received.	5.1% 4/78 The safety set consisted of all patients who received at least one dose of study medication. Patients were analyzed according to the treatment received.
Skin and subcutaneous tissue disorders Hyperhidrosis	10.3% 8/78 The safety set consisted of all patients who received at least one dose of study medication. Patients were analyzed according to the treatment received.	2.6% 2/78 The safety set consisted of all patients who received at least one dose of study medication. Patients were analyzed according to the treatment received.

Additional Information

Study Director

Novartis Pharmaceuticals

Phone: 862-778-8300

Email: trialandresults.registries@novartis.com

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 (i.e., data from all sites) in the clinical trial or disclosure of trial results in their entirety.
• Publication restrictions are in place

Restriction type: OTHER