Efficacy and Safety of Dapagliflozin, Added to Therapy of Patients With Type 2 Diabetes With Inadequate Glycemic Control on Insulin

NCT00673231 | Completed Phase 3 Results

• 1 other identifier: D1690C00006
• Study Type: interventional
• Target: 1,240
• Locations: 13 countries
• Sites: 92

Brief Summary

This study is being carried out to see if Dapagliflozin in addition to insulin is effective and safe in treating patients with type 2 diabetes when compared to placebo (identical looking inactive treatment) in addition to insulin

Conditions

Type 2 Diabetes

Keywords

Dapagliflozin; efficacy; safety; add on to insulin; Oral AntiDiabetic; Type 2 diabetes

Outcome Measures

Primary Outcomes (1)

• Adjusted Mean Change in HbA1c Levels

  To assess the efficacy of 2.5 mg, 5 mg and 10 mg dapagliflozin compared to placebo as add-on therapy to insulin in improving glycaemic control in participants with type 2 diabetes who have inadequate glycaemic control on ≥ 30 IU injectable insulin daily for at least 8 weeks prior to enrolment, as determined by the change in HbA1c levels from baseline to Week 24, excluding data after insulin up-titration.

  Baseline to Week 24

Secondary Outcomes (4)

• Adjusted Mean Change in Body Weight

  Baseline to Week 24

• Adjusted Mean Change in Calculated Mean Daily Insulin Dose

  Baseline to Week 24

• Proportion of Participants With Calculated Mean Daily Insulin Dose Reduction

  Baseline to Week 24

• Adjusted Mean Change in Fasting Plasma Glucose (FPG)

  Baseline to Week 24

Other Outcomes (1)

• Proportion of Participants With Lack of Glycemic Control

  Baseline to Week 24

Study Arms (4)

1

EXPERIMENTAL

2.5mg

Drug: Dapagliflozin

2

EXPERIMENTAL

5mg

Drug: Dapagliflozin

3

EXPERIMENTAL

10mg

Drug: Dapagliflozin

4

PLACEBO COMPARATOR

Drug: Placebo

Interventions

Dapagliflozin DRUG

tablet oral 2.5 mg total daily dose once daily 48 weeks (= 24 week randomised treatment period + 24 week study extension period I)

1

Placebo DRUG

Placebo

4

Eligibility Criteria

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

You may qualify if:

• Type 2 Diabetes
• Patients with HbA1c ≥7.5% and ≤10.5% and who are on a stable insulin regimen of at least 30 IU of injectable insulin per day either without any other oral antidiabetic drug or with a stable dose of oral antidiabetic drugs

You may not qualify if:

• Type 1 Diabetes
• Treatment with more than two additional oral antidiabetic drugs
• Moderate and severe renal (kidney) failure or dysfunction

Sponsors & Collaborators

• AstraZeneca: lead
• Bristol-Myers Squibb: collaborator

Study Sites (92)

Research Site

Fresno, California, United States

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Greenbrae, California, United States

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Roswell, Georgia, United States

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Chicago, Illinois, United States

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Springfield, Illinois, United States

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Indianapolis, Indiana, United States

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Omaha, Nebraska, United States

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Philadelphia, Pennsylvania, United States

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Corpus Christi, Texas, United States

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Dallas, Texas, United States

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Norfolk, Virginia, United States

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Richmond, Virginia, United States

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Tacoma, Washington, United States

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Salzburg, Austria

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Vienna, Austria

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Pleven, Bulgaria

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Rousse, Bulgaria

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Sofia, Bulgaria

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Varna, Bulgaria

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Calgary, Alberta, Canada

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Kelowna, British Columbia, Canada

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Langley, British Columbia, Canada

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Winnipeg, Manitoba, Canada

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Moncton, New Brunswick, Canada

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Mount Pearl, Newfoundland and Labrador, Canada

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St. John's, Newfoundland and Labrador, Canada

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Halifax, Nova Scotia, Canada

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Etobicoke, Ontario, Canada

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Kingston, Ontario, Canada

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London, Ontario, Canada

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Oakville, Ontario, Canada

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Scarborough Village, Ontario, Canada

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Thornhill, Ontario, Canada

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Chicoutimi, Quebec, Canada

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Longueuil, Quebec, Canada

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Mirabel, Quebec, Canada

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Sherbrooke, Quebec, Canada

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Lahti, Finland, Finland

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Helsinki, Finland

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Joensuu, Finland

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Jyväskylä, Finland

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Kuopio, Finland

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Oulu, Finland

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Seinäjoki, Finland

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Turku, Finland

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Bad Oeynhausen, Germany

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Dortmund, Germany

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Dresden, Germany

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Essen, Germany

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Frankfurt, Germany

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Magdeburg, Germany

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Münster, Germany

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Riesa, Germany

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Wolmirstedt, Germany

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Csongrád, Hungary

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Esztergom, Hungary

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Győr, Hungary

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Kaposvár, Hungary

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Kecskemét, Hungary

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Komárom, Hungary

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Miskolc, Hungary

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Székesfehérvár, Hungary

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Veszprém, Hungary

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Amersfoort, Netherlands

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Den Helder, Netherlands

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Leiden, Netherlands

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Rotterdam, Netherlands

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Brasov, Brașov County, Romania

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Tg Mures, Mureș County, Romania

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Bucharest, Romania

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Moscow, Russia

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Nizhny Novgorod, Russia

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Saint Petersburg, Russia

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Bratislava, Slovakia

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Dolný Kubín, Slovakia

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Košice, Slovakia

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Levice, Slovakia

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Lučenec, Slovakia

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Považská Bystrica, Slovakia

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Prešov, Slovakia

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Seville, Andalusia, Spain

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Sabadell (barcelona), Catalonia, Spain

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Madrid, Madrid, Spain

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Alicante, Valencia, Spain

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Reading, Berks, United Kingdom

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Aylesbury, Bucks, United Kingdom

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Ashford, United Kingdom

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Birmingham, United Kingdom

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Cardiff, United Kingdom

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Liverpool, United Kingdom

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Reading, United Kingdom

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Swansea, United Kingdom

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Related Publications (8)

• Natale P, Tunnicliffe DJ, Toyama T, Palmer SC, Saglimbene VM, Ruospo M, Gargano L, Stallone G, Gesualdo L, Strippoli GF. Sodium-glucose co-transporter protein 2 (SGLT2) inhibitors for people with chronic kidney disease and diabetes. Cochrane Database Syst Rev. 2024 May 21;5(5):CD015588. doi: 10.1002/14651858.CD015588.pub2.

  PMID: 38770818 DERIVED

• Aberle J, Menzen M, Schmid SM, Terkamp C, Jaeckel E, Rohwedder K, Scheerer MF, Xu J, Tang W, Birkenfeld AL. Dapagliflozin effects on haematocrit, red blood cell count and reticulocytes in insulin-treated patients with type 2 diabetes. Sci Rep. 2020 Dec 28;10(1):22396. doi: 10.1038/s41598-020-78734-z.

  PMID: 33372185 DERIVED

• Shah M, Stolbov L, Yakovleva T, Tang W, Sokolov V, Penland RC, Boulton D, Parkinson J. A model-based approach to investigating the relationship between glucose-insulin dynamics and dapagliflozin treatment effect in patients with type 2 diabetes. Diabetes Obes Metab. 2021 Apr;23(4):991-1000. doi: 10.1111/dom.14305. Epub 2021 Jan 25.

  PMID: 33368935 DERIVED

• Kohan DE, Fioretto P, Johnsson K, Parikh S, Ptaszynska A, Ying L. The effect of dapagliflozin on renal function in patients with type 2 diabetes. J Nephrol. 2016 Jun;29(3):391-400. doi: 10.1007/s40620-016-0261-1. Epub 2016 Feb 19.

  PMID: 26894924 DERIVED

• van Haalen HG, Pompen M, Bergenheim K, McEwan P, Townsend R, Roudaut M. Cost effectiveness of adding dapagliflozin to insulin for the treatment of type 2 diabetes mellitus in the Netherlands. Clin Drug Investig. 2014 Feb;34(2):135-46. doi: 10.1007/s40261-013-0155-0.

  PMID: 24243529 DERIVED

• Wilding JP, Woo V, Rohwedder K, Sugg J, Parikh S; Dapagliflozin 006 Study Group. Dapagliflozin in patients with type 2 diabetes receiving high doses of insulin: efficacy and safety over 2 years. Diabetes Obes Metab. 2014 Feb;16(2):124-36. doi: 10.1111/dom.12187. Epub 2013 Aug 29.

  PMID: 23911013 DERIVED

• Wilding JP, Woo V, Soler NG, Pahor A, Sugg J, Rohwedder K, Parikh S; Studiengruppe Dapagliflozin 006. [Long-term efficacy of dapagliflozin in patients with type 2 diabetes mellitus receiving high doses of insulin]. Dtsch Med Wochenschr. 2013 Apr;138 Suppl 1:S27-38. doi: 10.1055/s-0032-1305284. Epub 2013 Mar 25. German.

  PMID: 23529568 DERIVED

• Wilding JP, Woo V, Soler NG, Pahor A, Sugg J, Rohwedder K, Parikh S; Dapagliflozin 006 Study Group. Long-term efficacy of dapagliflozin in patients with type 2 diabetes mellitus receiving high doses of insulin: a randomized trial. Ann Intern Med. 2012 Mar 20;156(6):405-15. doi: 10.7326/0003-4819-156-6-201203200-00003.

  PMID: 22431673 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

dapagliflozin

Condition Hierarchy (Ancestors)

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

Limitations and Caveats

For participants who did not complete 24 weeks LOCF (last observation carried forward) was used. Only values prior to insulin up-titration were used for outcome measures except for mean daily insulin dose which was evaluated regardless of.

Results Point of Contact

• Title: Eva Johnsson
• Organization: AstraZeneca

ClinicalTrialTransparency@astrazeneca.com

Study Officials

• John Wilding, MD

  Clinical Sciences CentreUniversity Hospital AintreeLongmoor LaneLiverpool, UK

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 6, 2008
• First Posted: May 7, 2008
• Study Start: April 1, 2008
• Primary Completion: May 1, 2009
• Study Completion: January 1, 2011
• Last Updated: October 29, 2013
• Results First Posted: August 23, 2013

Record last verified: 2013-09

Locations

GB (8); HU (9); AU (2); CA (18); NL (4); RO (3); DE (9); SL (7); FI (8); ES (4); US (13); BU (4); RU (3)