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

Diabetes Mellitus, Type 2 Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01206647
• Other study ID #: AZ-SAX-001
• Status: Active, not recruiting
• Phase: Phase 4
• First received: September 15, 2010
• Last updated: September 21, 2010
• Start date: February 2010
• Est. completion date: February 2011

Study information

• Verified date: September 2010
• Source: ikfe-CRO GmbH
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Federal Institute for Drugs and Medical Devices
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 120
• Est. completion date: February 2011
• Est. primary completion date: February 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2

Intervention

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

Locations

Country	Name	City	State
Germany	Diabetologische Schwerpunktpraxis Dr. Lorra / Dr. Bonnermann	Bochum
Germany	Zentrum für klinische Studien Dresden, GWT-TUD GmbH	Dresden
Germany	Gemeinschaftspraxis Partner der Gesundheit	Essen
Germany	IKFE Institute for Clinical Research and Development	Mainz
Germany	Zentrum für Diabetes und Gefäßerkrankungen	Münster
Germany	Diabetes Zentrum Neuwied	Neuwied
Germany	ikfe Studiencenter Potsdam GmbH	Potsdam

Sponsors (3)

Lead Sponsor	Collaborator
ikfe-CRO GmbH	AstraZeneca, IKFE Institute for Clinical Research and Development

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	percentage of patients with stable HbA1c		26 ± 2 weeks (baseline to postbaseline values) at 4 week intervals	No
Secondary	impact of the switch on:	- Biomarkers of insulin resistance and ß-cell function	26 ± 2 weeks (baseline to postbaseline values)	No
Secondary	impact of the switch on:	- Biomarkers of cardiovaskular risk	26 ± 2 weeks (baseline to postbaseline values)	No
Secondary	impact of the switch on:	- Patient treatment satifaction	26 ± 2 weeks (baseline to postbaseline values)	No
Secondary	impact of the switch on:	- Treatment costs	26 ± 2 weeks (baseline to postbaseline values)	No
Secondary	impact of the switch on:	- Requirement of 3rd line OAD pioglitazone as rescue drug	26 ± 2 weeks (baseline to postbaseline values)	No
Secondary	impact of the switch on:	- oral Glucose Tolerance Test (oGTT)	26 ± 2 weeks (baseline to postbaseline values)	No
Secondary	impact of the switch on:	- Macrophagen activation (in a subpopulation at site 01 ikfe GmbH)	26 ± 2 weeks (baseline to postbaseline values)	No