Investigation of a Switch From Insulin Therapy to a Metformin & Saxagliptin Combination in Patients With Type 2 Diabetes Mellitus

The recruitment status of this study is unknown because the information has not been verified recently.
Verified September 2010 by ikfe-CRO GmbH.
Recruitment status was  Active, not recruiting
Sponsor:
Collaborators:
AstraZeneca
IKFE Institute for Clinical Research and Development
Information provided by:
ikfe-CRO GmbH
ClinicalTrials.gov Identifier:
NCT01206647
First received: September 15, 2010
Last updated: September 21, 2010
Last verified: September 2010
  Purpose

The purpose of this study is to investigate the success rate of a switch from insulin therapy to a metformin & saxagliptin combination in patients with type 2 diabetes mellitus.


Condition Intervention Phase
Diabetes Mellitus, Type 2
Drug: Metformin and Saxagliptin
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Investigation of a Switch From Insulin Therapy to a Metformin & Saxagliptin Combination in Patients With Type 2 Diabetes Mellitus

Resource links provided by NLM:


Further study details as provided by ikfe-CRO GmbH:

Primary Outcome Measures:
  • percentage of patients with stable HbA1c [ Time Frame: 26 ± 2 weeks (baseline to postbaseline values) at 4 week intervals ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • impact of the switch on: [ Time Frame: 26 ± 2 weeks (baseline to postbaseline values) ] [ Designated as safety issue: No ]
    - Biomarkers of insulin resistance and ß-cell function

  • impact of the switch on: [ Time Frame: 26 ± 2 weeks (baseline to postbaseline values) ] [ Designated as safety issue: No ]
    - Biomarkers of cardiovaskular risk

  • impact of the switch on: [ Time Frame: 26 ± 2 weeks (baseline to postbaseline values) ] [ Designated as safety issue: No ]
    - Patient treatment satifaction

  • impact of the switch on: [ Time Frame: 26 ± 2 weeks (baseline to postbaseline values) ] [ Designated as safety issue: No ]
    - Treatment costs

  • impact of the switch on: [ Time Frame: 26 ± 2 weeks (baseline to postbaseline values) ] [ Designated as safety issue: No ]
    - Requirement of 3rd line OAD pioglitazone as rescue drug

  • impact of the switch on: [ Time Frame: 26 ± 2 weeks (baseline to postbaseline values) ] [ Designated as safety issue: No ]
    - oral Glucose Tolerance Test (oGTT)

  • impact of the switch on: [ Time Frame: 26 ± 2 weeks (baseline to postbaseline values) ] [ Designated as safety issue: No ]
    - Macrophagen activation (in a subpopulation at site 01 ikfe GmbH)


Estimated Enrollment: 120
Study Start Date: February 2010
Estimated Study Completion Date: February 2011
Estimated Primary Completion Date: February 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
No Intervention: Control arm
The patients randomized to the control arm will continue their current therapy, as individually prescribed. Insulin will be administered via subcutaneous injection and OADs (if applicable) will be administered orally, as individually prescribed.
Experimental: Saxagliptin & metformin
Saxagliptin and metformin tablets will be administered orally. Pioglitazione (Rescue medication) tablets will be administered orally. Insulin glargine (Rescue medication) will be administered via subcutaneous injection as individually prescribed.
Drug: Metformin and Saxagliptin
Metformin 500mg/daily titrated to 2000mg/d in 4 Weeks (continued for 20 weeks) Saxagliptin 5 mg daily over complete trial

Detailed Description:

The following study is based on a previous clinical trial performed at ikfe GmbH in Mainz in 2006 and 2007 (PIOswitch). [2] The purpose of this trial was to demonstrate that type 2 diabetes patients treated with insulin can be effectively switched to a pioglitazone/glimepiride combination without loss of glycemic control. The study was performed with 100 patients, out of whom 76 were finally successfully switched, resulting in a cheaper and more convenient therapy with indications of an improved laboratory cardiovascular risk biomarker profile (Hohberg et al., Diabetes Obes. Metab. 11:464-471, 2009). [2] Glimeperide is an agent with unspecific stimulating effect on the ß-cell and is considered to accelerate the progression of the disease while still controlling blood glucose. In addition, it may cause hypoglycemia. The combination of pioglitazone with glimepiride was selected, because pioglitazone requires approx. 5-6 weeks for developing its full anti-diabetic efficacy and an immediate effect on glucose was required to avoid glycemic deterioration.

It is tempting to speculate that the combination of a drug providing ß-cell protection (like saxagliptin) with a drug effectively and rapidly lowering blood glucose through a different mechanism of action (metformin) instead of unspecific ß-cell stimulation would result in an even improved outcome without risk of hypoglycemia. The purpose of this study is to investigate the success rate of a switch from insulin therapy to a metformin & saxagliptin combination in patients with type 2 diabetes mellitus.

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Combination of OAD and basal insulin treatment (BOT) or intensified conventional therapy (ICT; > 2 injections of basal and prandial) or conventional insulin therapy (CIT; 1 or 2 injections of basal or biphasic)
  • HbA1c < 7.5 %
  • Age: 18-80 years inclusively
  • Duration of insulin therapy > 1 year
  • Insulin dose < 120 IU/day
  • Fasting C-peptide > 0.6 ng/l
  • Fasting glucose ≤ 210 mg/dl
  • Full legal, mental and physical ability to give informed consent
  • Patient consent that the general physician will be informed of trail participation
  • Experience in self measurement of blood glucose > 1 year

Exclusion Criteria:

  • Type 1 Diabetes mellitus
  • History of drug or alcohol abuse within the last five years prior to screening
  • History of severe or multiple allergies
  • Progressive fatal disease
  • History of significant cardiovascular, respiratory, gastrointestinal, hepatic (ALAT and/or ASAT > 3 times the normal reference range), neurological, psychiatric and/or haematological disease as judged by the investigator
  • Renal insufficiency or history of significant renal diseases (creatinine clearance lower than 60 ml/min determined using the Cockroft-Goult equation).
  • Contra-indications for study drugs including contraindications for the rescue drugs
  • Anamnestic history of hypersensitivity to the study drugs or to drugs with similar chemical structures
  • Pregnancy or breast feeding
  • Sexually active women of childbearing potential not consistently and correctly practicing birth control by implants, injectables, combined oral contraceptives, hormonal intrauterine devices (IUDs), sexual abstinence or vasectomised partner
  • Treatment with any other investigational drug within 3 months prior to screening
  • Lack of compliance or other similar reason, that according to investigator, precludes satisfactory participation in the study
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01206647

Locations
Germany
Diabetologische Schwerpunktpraxis Dr. Lorra / Dr. Bonnermann
Bochum, Germany, 44869
Zentrum für klinische Studien Dresden, GWT-TUD GmbH
Dresden, Germany, 01307
Gemeinschaftspraxis Partner der Gesundheit
Essen, Germany, 45355
IKFE Institute for Clinical Research and Development
Mainz, Germany, 55116
Zentrum für Diabetes und Gefäßerkrankungen
Münster, Germany, 48145
Diabetes Zentrum Neuwied
Neuwied, Germany, 56564
ikfe Studiencenter Potsdam GmbH
Potsdam, Germany, 14469
Sponsors and Collaborators
ikfe-CRO GmbH
AstraZeneca
IKFE Institute for Clinical Research and Development
Investigators
Principal Investigator: Andreas Pfützner, Prof.Dr.Dr. IKFE Institute for Clinical Research and Development
  More Information

No publications provided

Responsible Party: Prof. Andreas Pfuetzner, IKFE Institute for Clinical Research and Development
ClinicalTrials.gov Identifier: NCT01206647     History of Changes
Other Study ID Numbers: AZ-SAX-001
Study First Received: September 15, 2010
Last Updated: September 21, 2010
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Saxagliptin
Insulin
Metformin
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions
Dipeptidyl-Peptidase IV Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on April 17, 2014