Vildagliptin vs Sitagliptin add-on to Insulin - Impact on Glycemic Profile and Correlation of Hypoglycemic Episodes and Heart Function

NCT01686932 | Completed Phase 4 Results

• 1 other identifier: CLAF237ADE07
• Study Type: interventional
• Target: 51
• Locations: 1 country
• Sites: 11

Brief Summary

Vildagliptin and Sitagliptin both belong to the class of DPP-4 inhibitors, but differ in their pharmacokinetic profile as well as in their approved application (Vildagliptin, 2x 50 mg daily, Sitagliptin, 1x 100 mg daily). This leads to distinct results regarding postprandial blood-glucose normalization as well as protective properties regarding hypoglycemic episodes - especially during the night. Additionally, in type 1 diabetic patients a correlation has been described between hypoglycemia and abnormal heart function (QTc-elongation), which can have severe consequences for the patients. This study aims for the evaluation of the potency of both drugs to prevent and/or reduce hypoglycemic events in insulin-dependent type-2 diabetics and furthermore to evaluate the correlation of hypoglycemic episodes with changes in heart-function measured by Holter-ECG. The hypothesis is tested, if vildagliptin leads to a more favourable glycemic profile than sitagliptin and is more potent in protecting from nocturnal abnormalities in heart-function caused by undetected hypoglycemic episodes.

Conditions

Diabetes Mellitus Type 2

Keywords

vildagliptin; sitagliptin; continuous glucose monitoring (CGM); glycemic fluctuations; MAGE; impact of hypoglycemia on heart function (cardiac dysfuction measured via ECG); difference in glycemic profile of vildagliptin compared to sitagliptin

Outcome Measures

Primary Outcomes (1)

• Hypoglycemic Profile of Vildagliptin Compared to Sitagliptin Over 4 Days After 8 Weeks of Treatment in Period 1 & 2

  The hypoglycemic profile is defined as the area under the curve glucose-time profile obtained by continuous glucose monitoring Interstitial glucose values below 3.9 mmol/L (averaged over 5 minutes) were considered relevant for the estimation of the interstitial glucose AUC in the hypoglycemic range These AUC\<3.9mmol/L/5min. values were summed up over 4 days (unit: mmol/L/4d) or over 24 hours at measurement Days 2, 3, 4, and 5 (unit: mmol/L/24h). Lower values for AUC reflect less intense hypoglycemia.

  baseline and 0-24 hours post-dose on Days 2 to 5

Secondary Outcomes (10)

• Number of Hypoglycemic Events During Vildagliptin Treatment Compared to Sitagliptin Treatment.

  after 8 weeks period 1 and Period 2

• Mean Duration of Hypoglycemic Events (Min.) Measured With Continuous Glucose Monitoring (CGM) Over 4 Days After 8 Weeks of Treatment for Period 1 & Period 2

  after 8 weeks for Period 1 & Period 2

• Mean Amplitudes of Hypoglycemic Events (mmol/L) Measured With Continuous Glucose Monitoring (CGM) Over 4 Days After 8 Weeks of Treatment for Period 1 & Period 2

  after 8 weeks Period 1 & Period 2

• Number of Severe Hypoglycemic Events During Vildagliptin Treatment Compared to Sitagliptin Treatment After 8 Weeks of Treatment in Period 1 and Period 2

  after 8 weeks Period 1 & Period 2

• Glucose Fluctuations During the Day Under Vildagliptin Treatment Compared to Sitagliptin Treatment on Day 2 After 8 Weeks of Treatment Period 1 & Period 2

  Day 2 after 8 weeks of treatment Period 1 & Period 2

Study Arms (2)

Vildagliptin followed by Sitagliptin

EXPERIMENTAL

Period 1: vildagliptin 50mg BID for 8 weeks; followed by Washout then Period 2: sitagliptin 100mg QD for 8 weeks

Drug: Vildagliptin; Drug: Sitagliptin

Sitagliptin followed by Vildagliptin

EXPERIMENTAL

Period 1: sitagliptin 100mg QD for 8 weeks; followed by Washout then Period 2: vildagliptin 50mg BID for 8 weeks

Drug: Vildagliptin; Drug: Sitagliptin

Interventions

Vildagliptin DRUG

vildagliptin 50mg BID for 8 weeks

Also known as: Vildagliptin (Galvus) LAF237

Sitagliptin followed by Vildagliptin; Vildagliptin followed by Sitagliptin

Sitagliptin DRUG

sitagliptin 100mg QD for 8 weeks

Also known as: sitagliptin, Januvia

Sitagliptin followed by Vildagliptin; Vildagliptin followed by Sitagliptin

Eligibility Criteria

• Age: 40 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \. Written informed consent must be obtained before any assessment is performed.
• \. Ability to comply with all study requirements. 3. Patients with Type 2 diabetes treated with stable, once or twice daily doses (minimal dose of 0.3 unit/kg/day) of basal long-acting or intermediate-acting insulin alone or in pre-mixed combination with rapid-acting or short-acting insulin for at least 12 weeks prior to Visit 1. Stable is defined as ±10% of the Visit 1 dose during the previous 12 weeks.
• \. Patients receiving metformin must be on a stable dose of metformin (at least 1500 mg daily or a maximally tolerated dose) for at least 12 weeks prior to Visit 1. 5. HbA1c ≥7.5 to ≤ 9,0% at Visit 1 6. Known CV disease based on a documented history of one or more of pre-defined criteria 7. Age: ≥40 to ≤80 years at Visit 1

You may not qualify if:

• \. FPG ≥ 270 mg/dL (15 mmol/L) at Visit 1. 2. Use of any of the following medications as assessed at Visit 1:
• rapid or short acting insulin except in pre-mixed formulations with intermediate or long-acting insulin; insulin administration more frequently than twice-daily, or total insulin dose \< 0.3 unit/kg/day for the past 12 weeks
• use of any oral antidiabetic medication or GLP-1 analogues within the last 12 weeks, except metformin
• use of weight control products including weight-loss medications in the last 12 weeks.
• use of oral (≥7 consecutive days) or chronic parenteral or intra-articular corticosteroid treatment within the last 8 weeks. Inhaled or topical steroids without systemic effects will be allowed.
• treatment with growth hormone within the previous 6 months.
• treatment with any drug of known and frequent toxicity to a major organ, or that may interfere with the interpretation of the efficacy and safety data during the study.
• \. a history or evidence of any of the following at Visit 1:
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• acute metabolic conditions such a ketoacidosis, lactic acidosis or hyperosmolar state (including precoma and coma) within the past 6 months.
• current diagnosis of congestive heart failure (NYHA III or IV).
• myocardial infarction within the past 6 months.
• coronary artery bypass surgery or percutaneous coronary intervention within the past 6 months.
• Stroke, transient ischemic attack, or reversible ischemic neurologic deficit within the past 6 months.
• unstable angina within the past 6 months.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (11)

Novartis Investigative Site

Berlin, 10115, Germany

Location

Novartis Investigative Site

Berlin, 13055, Germany

Location

Novartis Investigative Site

Dortmund, 44137, Germany

Location

Novartis Investigative Site

Dresden, 01307, Germany

Location

Novartis Investigative Site

Elsterwerda, 04910, Germany

Location

Novartis Investigative Site

Falkensee, 14612, Germany

Location

Novartis Investigative Site

Magdeburg, 39112, Germany

Location

Novartis Investigative Site

Neuss, 41460, Germany

Location

Novartis Investigative Site

Potsdam, 14469, Germany

Location

Novartis Investigative Site

Sulzbach-Rosenberg, 92237, Germany

Location

Novartis Investigative Site

Wallerfing, 94574, Germany

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

Vildagliptin; 1-(((3-hydroxy-1-adamantyl)amino)acetyl)-2-cyanopyrrolidine; Sitagliptin Phosphate

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Nitriles; Organic Chemicals; Pyrrolidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Triazoles; Azoles; Pyrazines

Results Point of Contact

• Title: Study Director
• Organization: Novartis

862-778-8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 13, 2012
• First Posted: September 18, 2012
• Study Start: November 1, 2012
• Primary Completion: September 1, 2014
• Study Completion: September 1, 2014
• Last Updated: March 2, 2016
• Results First Posted: October 2, 2015

Record last verified: 2016-02

Locations

DE (11)