VERIFY:A Study to Compare Combination Regimen With Vildagliptin & Metformin Versus Metformin in Treatment-naïve Patients With Type 2 Diabetes Mellitus
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| ClinicalTrials.gov Identifier: NCT01528254 |
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Recruitment Status :
Completed
First Posted : February 7, 2012
Results First Posted : April 15, 2020
Last Update Posted : September 24, 2020
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| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Type 2 Diabetes Mellitus | Drug: Placebo of vildagliptin Drug: vildagliptin Drug: Metformin | Phase 4 |
This was a multi-center, double-blind, placebo-controlled, 2-arm, parallel group study with a run-in period and up to 5 years treatment period. Following a screening visit (Visit 1) and a screening period of up to 2 weeks, treatment-naïve patients, meeting all eligibility criteria entered the run-in period at Visit 2.
- Run-in period: At Visit 2, in all eligible patients, metformin treatment was initiated and/or up-titrated. At the end of the 3-week run-in period, patients who were able to tolerate a total dose of at least 1000 mg and up to 2000 mg daily proceeded to randomization and started in Period 1.
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Period 1 (vildagliptin/metformin combination versus metformin): At Visit 3, patients were randomized 1:1 to one of the following study regimens:
- Metformin up to 1000 mg bid plus vildagliptin 50mg bid or
- Metformin up to 1000 mg bid plus matching placebo bid
The duration of Period 1 could differ between patients depending on the time when the second of two HbA1c measurements taken at two consecutive visits after randomisation confirmed HbA1c ≥ 7.0%.
• Period 2 (vildagliptin/metformin combination versus vildagliptin add-on to metformin): In the case of two consecutive HbA1c measurements ≥7.0% from two consecutive study visits during Period 1, patients who were randomised to the placebo arm in Period 1 received vildagliptin 50 mg bid. Patients who were randomised to the active vildagliptin 50 mg bid arm in Period 1 continued to receive vildagliptin 50 mg bid. All patients continued to take their metformin dose unchanged. Period 2 remained masked to the patient and both patients and investigators remained masked to the treatment allocation in Period 1.
If, during Period 2, therapy intensification was required in accordance with the local guidelines, the patient entered Period 3. The duration of Period 2 could differ between patients. End of Period 2 was considered when insulin treatment was initiated, or alternatively when the patient was discontinued because insulin treatment was not initiated in Period 3.
• Period 3 (insulin initiation): In Period 3, patients were to be initiated on open-label insulin. The study drug regimen continued unchanged and remained masked to the patient in Period 3 and both patients and investigators remained masked to the treatment allocation in Period 1.
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 2004 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) |
| Primary Purpose: | Treatment |
| Official Title: | A 5-year Study to Compare the Durability of Glycemic Control of a Combination Regimen With Vildagliptin & Metformin Versus Standard-of-care Monotherapy With Metformin, Initiated in Treatment-naïve Patients With Type 2 Diabetes Mellitus |
| Actual Study Start Date : | March 30, 2012 |
| Actual Primary Completion Date : | April 4, 2019 |
| Actual Study Completion Date : | April 4, 2019 |
| Arm | Intervention/treatment |
|---|---|
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Active Comparator: Vilda 50mg bid + metformin
Metformin + vildagliptin
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Drug: vildagliptin
One tablet (50 mg oral) of vildagliptin in the morning and one tablet in the evening with or without food.
Other Name: LAF237 Drug: Metformin Twice daily (bid) regimen during or after meals at the same time as vildagliptin. |
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Experimental: Placebo + metformin
Metformin + Placebo of vildagliptin
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Drug: Placebo of vildagliptin
Other Name: Placebo Drug: Metformin Twice daily (bid) regimen during or after meals at the same time as vildagliptin. |
- Time to Initial Treatment Failure [ Time Frame: Visit 4 (Week 13) up to End of Study (Study Drug Discontinuation or Premature Subject Discontinuation) ]
Treatment failure was defined as two consecutive scheduled visits with HbA1c >= 7.0% (starting from 13 weeks after randomization) and the time to treatment failure was the number of days from randomization to the second of the consecutive scheduled visits.
Participants who discontinued the study for any reason during Period 1 were censored at the date of discontinuation. Participants who remained under the threshold (or whose measurement above the threshold was not confirmed at next scheduled visit) were censored at the date of last study visit.
- Rate of Loss in Glycemic Control During Period 1 [ Time Frame: Visit 5 (Week 26) to End of Period 1 ]
The rate of loss in glycemic control was estimated using the slope of HbA1c over time (years).
HbA1c data collected from Week 26 up to and including the end of Period 1 visit was included in the analysis. Baseline HbA1c was the sample obtained on day 1, or the sample obtained at an earlier visit (scheduled or unscheduled) which was closest to Day 1, if the Day 1 measurement was missing. End of Period 1 was defined as the final post-baseline assessment obtained at any visit within Period 1 (scheduled or unscheduled), up to the last scheduled visit.
- Rate of Loss in Glycemic Control in HbA1c Over Time During Period 2 [ Time Frame: From 26 weeks after start of Period 2 to end of Period 2 ]
The rate of loss in glycemic control was estimated using the slope of HbA1c over time (years).
HbA1c data collected from 26 weeks after the start of Period 2 to the end of Period 2 were included in the analysis, for participants who started insulin therapy in Period 3 or discontinued during Period 2 due to being unable or unwilling to initiate insulin therapy in period 3. Participants who completed the study in Period 1 or Period 2 were not be included in the analysis.
- Rate of Loss in Glycemic Control in Fasting Plasma Glucose (FPG) During Period 1 [ Time Frame: Visit 5 (Week 26) to End of Period 1 ]
Rate of loss in glycemic control was estimated using the slope of FPG over time (years).
FPG (fasting plasma glucose) data from Week 26 to the end of Period 1 was included in the analysis. Baseline FPG was the sample obtained on day 1, or the sample obtained at an earlier visit (scheduled or unscheduled) which was closest to Day 1, if the Day 1 measurement is missing. Participants who completed the study in Period 1 or Period 2 were not be included in the analysis.
- Rate of Loss in Glycemic Control in Fasting Plasma Glucose (FPG) Over Time During Period 2 [ Time Frame: From 26 weeks after start of Period 2 to end of Period 2 ]
Rate of loss in glycemic control was estimated using the slope of FPG over time (years).
FPG (fasting plasma glucose) data from 26 weeks after the start of Period 2 to then end of Period 2 was included in the analysis. Only participants who started insulin therapy in Period 3 or discontinued during Period 2 due to being unable or unwilling to initiate insulin therapy in period 3 were included. Participants who completed the study in Period 1 or Period 2 were not be included in the analysis.
- Rate of Loss of Beta Cell Function From Baseline to End of Study [ Time Frame: Visit 4 (Week 13), End of Period 1, End of Period 2, End of Study (Study Drug Discontinuation or Premature Subject Discontinuation) ]The rate of change of beta cell function was assessed using the slope of AUC of ISR/G over time (years) where AUC of ISR/G is defined as (Area under curve of Insulin secretion rate (derived using c-peptide))/(Area under curve of Glucose), using meal-test data from 0 to 120 minutes. Baseline AUC of ISR/G was derived based on samples obtained on day 1, or samples obtained at an earlier visit (scheduled or unscheduled) which was closest to Day 1, if the Day 1 measurements were missing. Three analyses were included, using data from Week 13 to the end of Period 1, end of Period 2 and end of study, respectively.
- Rate of Change in Insulin Sensitivity From Baseline to End of Study [ Time Frame: Visit 4 (Week 13), End of Period 1, End of Period 2, End of Study (Study Drug Discontinuation or Premature Subject Discontinuation) ]The rate of change of insulin sensitivity is assessed using the slope of OGIS over time (years) where Oral glucose insulin sensitivity (OGIS) was calculated as a function of glucose and insulin, using meal-test data from 0 to 120 minutes. Baseline OGIS is derived based on samples obtained on day 1, or samples obtained at an earlier visit (scheduled or unscheduled) which was closest to Day 1, if the Day 1 measurements are missing. Three analyses were included, using data from Week 13 to the end of Period 1, end of Period 2 and end of study, respectively.
- Percentage of Participants With Adverse Events, Serious Adverse Events and Death [ Time Frame: From first dose of study treatment until End of Study (Study Drug Discontinuation or Premature Subject Discontinuation) ]Analysis of absolute and relative frequencies for treatment emergent Adverse Event (AE), Serious Adverse Event (SAE) and Deaths by primary System Organ Class (SOC) in each treatment arm to demonstrate that LAF237 is safe for the treatment of naïve patients with type 2 diabetes mellitus through the monitoring of relevant clinical and laboratory safety parameters.
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| Ages Eligible for Study: | 18 Years to 70 Years (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Key Inclusion Criteria:
- Type 2 Diabetes Mellitus (T2DM) diagnosed ≤ 24 months ago
- glycosylated hemoglobin (HbA1c) ≥6.5% and ≤7.5% at Visit 1
- Treatment-naïve.
- Body mass index (BMI) ≥22 and ≤40 kg/m2 at Visit 1
Key Exclusion Criteria:
- Pregnant or nursing (lactating) women
- Fasting plasma glucose (FPG) ≥ 270 mg/dL (≥ 15.0 mmol/L)
- Previous or current participation in any vildagliptin clinical study.
- History of hypersensitivity to dipeptidyl peptidase-4 (DPP-4) inhibitors.
- Concurrent medical condition that may interfere with the interpretation of efficacy and safety data during the study.
- Donation of blood or significant blood loss equaling to at least one unit of blood within the past 2 weeks of start of study or a blood transfusion within the past 12 weeks or planned regular transfusions during the study period.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01528254
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| Study Director: | Novartis Pharmaceuticals | Novartis Pharmaceuticals |
Documents provided by Novartis ( Novartis Pharmaceuticals ):
| Responsible Party: | Novartis Pharmaceuticals |
| ClinicalTrials.gov Identifier: | NCT01528254 |
| Other Study ID Numbers: |
CLAF237A23156 2011-003712-23 ( EudraCT Number ) |
| First Posted: | February 7, 2012 Key Record Dates |
| Results First Posted: | April 15, 2020 |
| Last Update Posted: | September 24, 2020 |
| Last Verified: | September 2020 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | Yes |
| Plan Description: | Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com |
| Studies a U.S. FDA-regulated Drug Product: | No |
| Studies a U.S. FDA-regulated Device Product: | No |
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Type 2 Diabetes Mellitus Vildagliptin Elderly Patients |
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Diabetes Mellitus Diabetes Mellitus, Type 2 Glucose Metabolism Disorders Metabolic Diseases Endocrine System Diseases Metformin Vildagliptin |
Hypoglycemic Agents Physiological Effects of Drugs Dipeptidyl-Peptidase IV Inhibitors Protease Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action |