Treatment Effect of Saxagliptin Compared With Placebo in Patients With Type 2 Diabetes and Renal Impairment

A Short-term 12-Week, Multi-centre, Randomized, Parallel-group, Double-blind, Placebo-controlled Study to Evaluate the Treatment Effect of Saxagliptin Compared With Placebo in Adult Patients With Type 2 Diabetes and Renal Impairment (Moderate, Severe, and End-Stage) With an Additional 40-week, Randomized, Double-blind, Placebo-controlled Long-term Observational Period.

Saxagliptin is a new investigational medication being developed for treatment of type 2 diabetes. This study is designed to test the efficacy of once daily saxagliptin in renally impaired patients.

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes
• Intervention / Treatment: Drug: Placebo; Drug: Saxagliptin

• Study Type: Interventional
• Enrollment (Actual): 572
• Phase: Phase 3

Contacts and Locations

Study Locations

• Belarus
  • Brest, Belarus
    • Research Site
  • Gomel, Belarus
    • Research Site
  • Minsk, Belarus
    • Research Site
• Bulgaria
  • Dimitrovgrad, Bulgaria
    • Research Site
  • Sofia, Bulgaria
    • Research Site
  • Veliko Tarnovo, Bulgaria
    • Research Site
• Croatia
  • Karlovac, Croatia
    • Research Site
  • Osijek, Croatia
    • Research Site
  • Rijeka, Croatia
    • Research Site
  • Split, Croatia
    • Research Site
  • Zagreb, Croatia
    • Research Site
• Czech Republic
  • Moravsky Krumlov, Czech Republic
    • Research Site
  • Praha 10, Czech Republic
    • Research Site
  • Teplice, Czech Republic
    • Research Site
  • Usti Nad Labem, Czech Republic
    • Research Site
  • Znojmo, Czech Republic
    • Research Site
• Estonia
  • Tallinn, Estonia
    • Research Site
• Germany
  • Dieburg, Germany
    • Research Site
  • Dusseldorf, Germany
    • Research Site
  • Hannover, Germany
    • Research Site
  • Heidelberg, Germany
    • Research Site
  • Mannheim, Germany
    • Research Site
• Hungary
  • Debrecen, Hungary
    • Research Site
  • Gyor, Hungary
    • Research Site
  • Kalocsa, Hungary
    • Research Site
  • Kecskemet, Hungary
    • Research Site
  • Zalaegerszeg, Hungary
    • Research Site
• Latvia
  • Riga, Latvia
    • Research Site
• Lithuania
  • Kaunas, Lithuania
    • Research Site
  • Klaipeda, Lithuania
    • Research Site
  • Panevezys, Lithuania
    • Research Site
  • Vilnius, Lithuania
    • Research Site
• Poland
  • Bialystok, Poland
    • Research Site
  • Ciechanow, Poland
    • Research Site
  • Golub Dobrzyn, Poland
    • Research Site
  • Grodzisk Mazowiecki, Poland
    • Research Site
  • Katowice, Poland
    • Research Site
  • Krakow, Poland
    • Research Site
  • Makow Mazowiecki, Poland
    • Research Site
  • Radom, Poland
    • Research Site
  • Szczecin, Poland
    • Research Site
  • Warszawa, Poland
    • Research Site
  • Wroclaw, Poland
    • Research Site
  • Zabrze, Poland
    • Research Site
  • 90-153
    • Lodz, 90-153, Poland
      • Research Site
• Romania
  • Bacau, Romania
    • Research Site
  • Brasov, Romania
    • Research Site
  • Bucharest, Romania
    • Research Site
  • Bucuresti, Romania
    • Research Site
  • Sf Gheorghe, Romania
    • Research Site
  • Satu Mare
    • Satu-mare, Satu Mare, Romania
      • Research Site
• Russian Federation
  • Chelyabinsk, Russian Federation
    • Research Site
  • Moscow, Russian Federation
    • Research Site
  • Ryazan, Russian Federation
    • Research Site
  • St.petersburg, Russian Federation
    • Research Site
  • Yaroslavl, Russian Federation
    • Research Site
• Ukraine
  • Dnipropetrovsk, Ukraine
    • Research Site
  • Ivano-frankivsk, Ukraine
    • Research Site
  • Kharkiv, Ukraine
    • Research Site
  • Kyiv, Ukraine
    • Research Site
  • Mykolayiv, Ukraine
    • Research Site
  • Sumy, Ukraine
    • Research Site
  • Ternopil, Ukraine
    • Research Site
  • Zaporizhzhya, Ukraine
    • Research Site
• United States
  • California
    • Concord, California, United States
      • Research Site
    • Sacramento, California, United States
      • Research Site
  • Colorado
    • Denver, Colorado, United States
      • Research Site
  • Kansas
    • Topeka, Kansas, United States
      • Research Site
  • Maryland
    • Baltimore, Maryland, United States
      • Research Site
  • Montana
    • Great Falls, Montana, United States
      • Research Site
  • North Carolina
    • Greenville, North Carolina, United States
      • Research Site
    • Morehead City, North Carolina, United States
      • Research Site
  • Ohio
    • Cincinnati, Ohio, United States
      • Research Site
  • Texas
    • Corpus Christi, Texas, United States
      • Research Site
  • West Virginia
    • Charleston, West Virginia, United States
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Diagnosed with type 2 diabetes
• Documented history of CrCl <50 ml/min within the 3 months prior to enrollment
• HbA1c ≥7.0% and ≤11.0%

Exclusion Criteria:

• Type 1 diabetes, history of diabetic ketoacidosis or hyposmolar non-ketonic coma
• Previous or current treatment with any DPP-IV inhibitor and/or GLP-1 mimetic.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Saxa; Saxagliptin	Drug: Saxagliptin; 2.5 mg once daily oral dose; Other Names: Onglyza
No Intervention: Placebo; Placebo to match	Drug: Placebo; Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Absolute Change From Baseline in Glycosylated Haemoglobin A1c (HbA1c) Level to Week 12 Last Observation Carried Forward (LOCF)	Adjusted* mean change from baseline in HbA1c achieved with saxagliptin 2.5 mg once daily versus placebo at Week 12 (Full Analysis Set). HbA1c is a continuous measure, the change from baseline for each participant is calculated at the Week 12 value minus the baseline value.	Baseline , Week 12 (LOCF)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Absolute Change From Baseline in Fasting Plasma Glucose (FPG) to Week 12 (LOCF)- Moderate Renal Impairment Subgroup	Adjusted* mean change from baseline in fasting plasma glucose (FPG) achieved with saxagliptin 2.5 mg once daily versus placebo at Week 12 (Full Analysis Set) for the moderate renal impairment subgroup. FPG is a continuous measure, the change from baseline for each participant is calculated at the Week 12 value minus the baseline value.	Baseline, Week 12 (LOCF)
Absolute Change From Baseline in Fasting Plasma Glucose (FPG) to Week 12 (LOCF) - Severe Renal Impairment Subgroup	Adjusted* mean change from baseline in fasting plasma glucose (FPG) achieved with saxagliptin 2.5 mg once daily versus placebo at Week 12 (Full Analysis Set) for the severe renal impairment subgroup. FPG is a continuous measure, the change from baseline for each participant is calculated at the Week 12 value minus the baseline value.	Baseline, Week 12 (LOCF)
Absolute Change From Baseline in Fasting Plasma Glucose (FPG) to Week 12 (LOCF) - End-Stage Renal Impairment Subgroup	Adjusted* mean change from baseline in fasting plasma glucose (FPG) achieved with saxagliptin 2.5 mg once daily versus placebo at Week 12 (Full Analysis Set) for the end-stage renal impairment subgroup. FPG is a continuous measure, the change from baseline for each participant is calculated at the Week 12 value minus the baseline value.	Baseline, Week 12 (LOCF)
Absolute Change From Baseline in Fasting Plasma Glucose (FPG) to Week 12 (LOCF) - Moderate Renal Impairment Subgroup	Adjusted* mean change from baseline in fasting plasma glucose (FPG) achieved with saxagliptin 2.5 mg once daily versus placebo at Week 12 (Full Analysis Set) for the moderate renal impairment subgroup. FPG is a continuous measure, the change from baseline for each participant is calculated at the Week 12 value minus the baseline value.	Baseline, Week 12 (LOCF)
Absolute Change From Baseline in Glycosylated Haemoglobin A1c (HbA1c) Level to Week 52	Adjusted* mean change from baseline in HbA1c achieved with saxagliptin 2.5 mg once daily versus placebo at Week 52 (Full Analysis Set). HbA1c is a continuous measure, the change from baseline for each participant is calculated at the Week 52 value minus the baseline value.	Baseline , Week 52
Absolute Change From Baseline in Fasting Plasma Glucose (FPG) to Week 52 - Moderate Renal Impairment Subgroup	Adjusted* mean change from baseline in fasting plasma glucose (FPG) achieved with saxagliptin 2.5 mg once daily versus placebo at Week 52 (Full Analysis Set) for the moderate renal impairment subgroup. FPG is a continuous measure, the change from baseline for each participant is calculated at the Week 52 value minus the baseline value.	Baseline, Week 52
Absolute Change From Baseline in Fasting Plasma Glucose (FPG) to Week 52 - Severe Renal Impairment Subgroup	Adjusted* mean change from baseline in fasting plasma glucose (FPG) achieved with saxagliptin 2.5 mg once daily versus placebo at Week 52 (Full Analysis Set) for the severe renal impairment subgroup. FPG is a continuous measure, the change from baseline for each participant is calculated at the Week 52 value minus the baseline value.	Baseline, Week 52
Absolute Change From Baseline in Fasting Plasma Glucose (FPG) to Week 52 - End-Stage Renal Impairment Subgroup	Adjusted* mean change from baseline in fasting plasma glucose (FPG) achieved with saxagliptin 2.5 mg once daily versus placebo at Week 52 (Full Analysis Set) for the end-stage renal impairment subgroup. FPG is a continuous measure, the change from baseline for each participant is calculated at the Week 52 value minus the baseline value.	Baseline, Week 52
Absolute Change From Baseline in Fasting Plasma Glucose (FPG) to Week 52 - Moderate Renal Impairment Subgroup	Adjusted* mean change from baseline in fasting plasma glucose (FPG) achieved with saxagliptin 2.5 mg once daily versus placebo at Week 52 (Full Analysis Set) for the moderate renal impairment subgroup. FPG is a continuous measure, the change from baseline for each participant is calculated at the Week 52 value minus the baseline value	Baseline, Week 52

Collaborators and Investigators

• Sponsor: AstraZeneca
• Collaborators: Bristol-Myers Squibb
• Investigators: Study Director: Peter Öhman, MD, PhD, AstraZeneca; Study Chair: Deborah Price, MSc, AstraZeneca

Publications and helpful links

General Publications

• Nowicki M, Rychlik I, Haller H, Warren ML, Suchower L, Gause-Nilsson I; D1680C00007 Investigators. Saxagliptin improves glycaemic control and is well tolerated in patients with type 2 diabetes mellitus and renal impairment. Diabetes Obes Metab. 2011 Jun;13(6):523-32. doi: 10.1111/j.1463-1326.2011.01382.x.

Study record dates

Study Major Dates

• Study Start: January 1, 2008
• Primary Completion (Actual): June 1, 2009
• Study Completion (Actual): March 1, 2010

Study Registration Dates

• First Submitted: January 31, 2008
• First Submitted That Met QC Criteria: February 12, 2008
• First Posted (Estimate): February 13, 2008

Study Record Updates

• Last Update Posted (Estimate): May 19, 2011
• Last Update Submitted That Met QC Criteria: May 16, 2011
• Last Verified: May 1, 2011

More Information

Terms related to this study

• Keywords: HbA1c; Renal Impairment; DPP-4 inhibitors; incretins
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Kidney Diseases; Urologic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Renal Insufficiency; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Protease Inhibitors; Incretins; Dipeptidyl-Peptidase IV Inhibitors; Saxagliptin
• Other Study ID Numbers: D1680C00007; EudraCT number 2007-004951-12

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No