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Diabetes Mellitus Type 2Phase 4CGM-VISITNCT01686932

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

A Phase 4 study testing Vildagliptin and Sitagliptin in people with Diabetes Mellitus Type 2, run by Novartis Pharmaceuticals at 11 sites in Germany.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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). Read more about this study

Who is it for?
Ages 40 to 80 years
Conditions the study is for
Diabetes Mellitus Type 2
What is being tested?
Vildagliptin and Sitagliptin
Could I receive a placebo?
No, everyone receives an active treatment
How many people
51 participants
Where
11 sitesGermany
Study dates
Nov 2012to Sep 2014
Phase
Phase 4
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 40 to 80 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 1. Written informed consent must be obtained before any assessment is performed.
  • 2. 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.
  • 4. 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

Who cannot join

  • 1. 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.
Show all 41Show fewer
  • 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.
  • 3. a history or evidence of any of the following at Visit 1:
  • <!-- -->
  • 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.
  • sustained and clinically relevant ventricular arrhythmia (patients with premature ventricular contractions if deemed not clinically significant may be enrolled).
  • Patients with permanent atrial fibrillation or pacemaker.
  • active substance abuse, alcohol abuse and history of alcohol-related diseases within the past 2 years.
  • type 1 diabetes, monogenic diabetes, diabetes resulting from pancreatic injury, or secondary forms of diabetes (e.g. Cushing's syndrome or acromegaly-associated diabetes).
  • malignancy of an organ system (other than localized basal cell carcinoma of the skin) treated or untreated, within the past 5 years, regardless of whether there is evidence of local recurrence or metastases.
  • hepatic disorder defined as:
  • acute or chronic liver disease, evidence of hepatitis, cirrhosis or portal hypertension.
  • history of imaging abnormalities that suggest liver disease (except hepatic steatosis), such as portal hypertension, capsule scalloping, cirrhosis.
  • acute infections which may affect blood glucose control within the past 4 weeks.
  • 4. any of the following significant laboratory abnormalities as assessed at Visit 1:
  • <!-- -->
  • clinically significant increase or reduction in thyroid stimulating hormone (TSH) outside of the normal range.
  • clinically significant renal dysfunction: glomerular filtration rate (GFR) <50 mL/min/1.73m2 (via MDRD formula).
  • Patients on metformin with a GFR <60 mL/min/1.73m2 (via MDRD formula).
  • alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) > 2 x upper limit of normal (ULN) at Visit 1, confirmed by repeated measurements within 3 working days.
  • total bilirubin > 2 x ULN and/or direct bilirubin > 1 x ULN confirmed by repeated measurements within 3 working days.
  • positive Hepatitis B surface antigen (HBsAg).
  • positive Hepatitis C virus (HCV) antibody test (anti-HCV).
  • elevated fasting triglycerides (TGs) > 500mg/dL (5.65mmol/L), confirmed by a repeated measurements within 3 working days.
  • clinically significant laboratory abnormalities which, in the opinion of the investigator, cause the patient to be considered inappropriate for inclusion in the study.
  • 5. any of the following electrocardiographic abnormalities at Visit 1:
  • <!-- -->
  • second or third degree atrio-ventricular block.
  • A QTc of > 440 ms.
  • clinically significant electrocardiogram (ECG) abnormalities which, in the opinion of the investigator, may cause the patient to be considered inappropriate for inclusion in the study
  • Other protocol-defined inclusion/exclusion criteria may apply.

Trial locations and contacts

11 sites in 1 country.

11 sites in 1 country

Germany11 sites

  • Novartis Investigative Site

    Berlin, 10115

  • Novartis Investigative Site

    Berlin, 13055

  • Novartis Investigative Site

    Dortmund, 44137

  • Novartis Investigative Site

    Dresden, 01307

  • Novartis Investigative Site

    Elsterwerda, 04910

  • Novartis Investigative Site

    Falkensee, 14612

  • Novartis Investigative Site

    Magdeburg, 39112

  • Novartis Investigative Site

    Neuss, 41460

  • Novartis Investigative Site

    Potsdam, 14469

  • Novartis Investigative Site

    Sulzbach-Rosenberg, 92237

  • Novartis Investigative Site

    Wallerfing, 94574

Other trials in Germany

About this study

Official title: Multicentric Cross-over Trial to Assess the Glycemic Profiles on 8 Weeks of Vildagliptin and Sitagliptin Treatment, Each, in Type-2 Diabetic Patients With a Pre-existing Cardiovascular Disease Pre-treated With Insulin, Using a PROBE-design

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.

Being tested
Vildagliptin, Sitagliptin
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
Medical subject headings
Diabetes Mellitus, Type 2

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • VildagliptinDrug

    Also called Vildagliptin (Galvus) LAF237

    vildagliptin 50mg BID for 8 weeks

  • SitagliptinDrug

    Also called sitagliptin, Januvia

    sitagliptin 100mg QD for 8 weeks

Study groups in NCT01686932
Study groupRoleWhat they receive
Vildagliptin followed by SitagliptinExperimentalPeriod 1: vildagliptin 50mg BID for 8 weeks; followed by Washout then Period 2: sitagliptin 100mg QD for 8 weeks
Receives: Drug: Vildagliptin; Drug: Sitagliptin
Sitagliptin followed by VildagliptinExperimentalPeriod 1: sitagliptin 100mg QD for 8 weeks; followed by Washout then Period 2: vildagliptin 50mg BID for 8 weeks
Receives: Drug: Vildagliptin; Drug: Sitagliptin

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

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

Secondary outcomes (10)

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

    Hypoglycemic events are defined as blood glucose values <70 mg/dL measured by a self-monitored blood glucose (SMBG) or continuous glucose monitoring (CGM) measurement regardless of any symptoms suggestive of low blood glucose.

    Measured: after 8 weeks period 1 and Period 2

  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

    the mean duration of hypoglycemic events is detected by continuous glucose monitoring (CGM)measurement.

    Measured: after 8 weeks for Period 1 & Period 2

  3. 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

    To evaluate by CGM measurement the grade of severity of hypoglycemia measured as the mean amplitude over 4 days after 8 weeks of treatment in Period 1 \& Period 2

    Measured: after 8 weeks Period 1 & Period 2

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

    Severe hypoglycemic events are defined as any episode requiring the assistance of another party or measured plasma glucose levels of <40 mg /dL. Assessed by self-monitored blood glucose (SMBG)After 8 weeks of treatment in Period 1 and Period 2

    Measured: after 8 weeks Period 1 & Period 2

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

    Glucose fluctuations are assessed by the mean amplitude of glycemic excursions (MAGE) and standard deviations (SD) (Service et al., 1970). on day 2 after 8 weeks of treatment Period 1 \& Period 2

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

  6. Number of Participants With ECG Abnormalities Depending on Hypoglycemic Events After 8 Weeks of Treatment Period 1 & Period 2

    ECG abnormalities are defined as either: • Occurrence of >30 ventricular extrasystoles (VES) per hour or • Occurrence of ≥2 consecutive VES (Couplets) or • Occurrence of ≥3 consecutive VES (Triplets) or • QT-time corrected for heart rate (QTc) >440 ms. after 8 weeks of treatment Period 1 \& Period 2

    Measured: after 8 weeks of treatment Period 1 & Period 2

  7. Change From Baseline of Inflammatory Biomarkers High Sensitivity C-reactive Protein (hsCRP) After 8 Weeks of Treatment in Period 1 & Period 2

    The inflammatory biomarkers hsCRP was assessed at baseline and after 8 weeks of treatment Period 1 \& Period 2

    Measured: Baseline, after 8 weeks Period 1 & Period 2

  8. Change From Baseline of Inflammatory Biomarkers Interleukin 6 (IL-6) After 8 Weeks of Treatment in Period 1 & Period 2

    The inflammatory biomarkers IL-6 was assessed at baseline and after 8 weeks of treatment Period 1 \& Period 2

    Measured: Baseline, after 8 weeks Period 1 & Period 2

  9. Percentage Change From Baseline of Pro-insulin/C-peptide Ratios After 8 Weeks of Treatment Period 1 & Period 2

    Percentage Change from baseline of pro-insulin/C-peptide ratios after 8 weeks of treatment Period 1 \& Period 2 Higher pro-insulin / C-peptide ratios (expressing disproportional hyperproinsulinemia) may be associated with increasing beta cell dysfunction and more inefficient pro-insulin processing

    Measured: Baseline, after 8 weeks Period 1 & Period 2

  10. Number of Occurrence of Pre-defined ECG Findings During 4 Days of Continuous ECG Monitoring at Baseline and in the 8th Week of Periods 1 and 2

    Number of Occurrence of pre-defined ECG findings during 4 days of continuous ECG monitoring at baseline and in the 8th week of Periods 1 and 2. ECG data were continuously recorded and analyzed over a period of 4 days simultaneously with continuous glucose monitoring. It assessed number of any Vertical Electric(al) Sounding (VES), number of 2 consecutive VES [couplets], and number of >3 consecutive VES [salves]

    Measured: after 8 weeks Period 1 & Period 2

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted18 Sep 2012 (estimated)
  2. Study startNov 2012
  3. Primary completionSep 2014
  4. Study completionSep 2014

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 4
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Crossover
Masking
None (open label)
Enrolment
51 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01686932
Sponsor's protocol ID
CLAF237ADE07
Acronym
CGM-VISIT
Status last verified
Feb 2016
First submitted
13 Sep 2012
Last updated
2 Mar 2016
Data monitoring committee
No

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Vildagliptin and Sitagliptin in people with Diabetes Mellitus Type 2, run by Novartis Pharmaceuticals at 11 sites in Germany.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 41 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 2 Mar 2016. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 11 sites in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 2 Oct 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Hypoglycemic Profile of Vildagliptin Compared to Sitagliptin Over 4 Days After 8 Weeks of Treatment in Period 1 & 2 (time frame: baseline and 0-24 hours post-dose on Days 2 to 5). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01686932.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Mar 2016.

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