Evaluation of Dapagliflozin Taken Twice-daily

Type 2 Diabetes Clinical Trial

Official title:

A 16-week, Multicentre, Randomised, Double-Blind, Placebo-Controlled Phase III Study to Evaluate the Safety and Efficacy of Dapagliflozin 2.5 mg BID, 5 mg BID and 10 mg QD Versus Placebo in Patients With Type 2 Diabetes Who Are Inadequately Controlled on Metformin-IR Monotherapy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01217892
• Other study ID #: D1691C00003
• Status: Completed
• Phase: Phase 3
• First received: October 7, 2010
• Last updated: October 16, 2014
• Start date: November 2010
• Est. completion date: August 2011

Study information

• Verified date: October 2014
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Federal Institute for Drugs and Medical DevicesHungary: National Institute of PharmacyRomania: National Medicines AgencySlovakia: State Institute for Drug ControlSouth Africa: Medicines Control CouncilSwitzerland: SwissmedicUkraine: Ministry of Health
• Study type: Interventional

Clinical Trial Summary

This study is being carried out to see if dapagliflozin - administered in a daily dose of 2.5 mg given twice a day or 5 mg twice a day or 10mg once daily - in addition to metformin, is beneficial in diabetes treatment, and if so, how it compares to treatment with metformin alone.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 400
• Est. completion date: August 2011
• Est. primary completion date: August 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 77 Years

Eligibility

Inclusion Criteria:

• Provision of informed consent prior to any study specific procedures

• Diagnosis of T2DM

• Current antihyperglycaemic treatment with metformin immediate release formulation monotherapy >/= 1500 mg/day at a stable dose for at least 10 weeks prior to enrolment. Other treatment with OADs within the 10 weeks prior to enrolment is not permitted.

• HbA1c = 6.7% and =10.5%, based on central laboratory values from Screening Visit, and Enrolment Visit 1.

Exclusion Criteria:

• Diagnosis of Type 1 diabetes mellitus, known diagnosis of Maturity Onset Diabetes of the Young (MODY) or secondary causes of diabetes mellitus

• History of diabetic ketoacidosis

• Symptoms of poorly controlled diabetes including, but not limited to, marked polyuria, polydipsia, and/or greater than 10% weight loss during the 3 months prior to enrolment

• FPG >270 mg/dL (>15.0 mmol/L)

• BMI >45 kg/m2

Study Design

Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Diabetes Mellitus, Type 2
• Type 2 Diabetes

Intervention

Drug:
• dapagliflozin
2.5 mg tablet, taken orally, twice daily
• dapagliflozin
5 mg tablet taken orally, twice daily
• dapagliflozin
10 mg tablet taken orally, once daily
• metformin
>/= 1500 mg total daily dose, tablets taken orally, twice daily
• placebo
placebo

Locations

Country	Name	City	State
Germany	Research Site	Asslar
Germany	Research Site	Berlin
Germany	Research Site	Biberach A.d. Riss
Germany	Research Site	Bosenheim
Germany	Research Site	Dippoldiswalde
Germany	Research Site	Falkensee
Germany	Research Site	Meissen
Germany	Research Site	Munchen
Germany	Research Site	Neuwied
Germany	Research Site	Pirna
Germany	Research Site	Wahlstedt
Hungary	Research Site	Balatonfured
Hungary	Research Site	Budapest
Hungary	Research Site	Csongrad
Hungary	Research Site	Debrecen
Hungary	Research Site	Gyongyos
Hungary	Research Site	Kecskemet
Hungary	Research Site	Mako
Hungary	Research Site	Nyiregyhaza
Hungary	Research Site	TAT
Hungary	Research Site	Zalaegerszeg
Romania	Research Site	Brasov
Romania	Research Site	Bucuresti
Romania	Research Site	Iasi
Romania	Research Site	Sibiu
Romania	Research Site	Suceava
Slovakia	Research Site	Banska Bystrica
Slovakia	Research Site	Bratislava
Slovakia	Research Site	Dolny Kubin
Slovakia	Research Site	Kosice
Slovakia	Research Site	Lucenec
Slovakia	Research Site	Namestovo
Slovakia	Research Site	Piestany
Slovakia	Research Site	Prievidza
Slovakia	Research Site	Rimavska Sobota
Slovakia	Research Site	Ruzomberok
Slovakia	Research Site	Zilina
South Africa	Research Site	Cape Town
South Africa	Research Site	Durban
South Africa	Research Site	Johannesburg
South Africa	Research Site	Umkomaas
South Africa	Research Site	Verulam	Kwa Zulu Natal
Switzerland	Research Site	Basel
Switzerland	Research Site	Bern
Switzerland	Research Site	Chur	Graubunden
Switzerland	Research Site	Geneva 14
Switzerland	Research Site	Kreuzlingen
Switzerland	Research Site	Lugano
Switzerland	Research Site	Rorschach
Ukraine	Research Site	Dnipropetrov'sk
Ukraine	Research Site	Kiev
Ukraine	Research Site	Vinnytsia
Ukraine	Research Site	Vynnitsa
Ukraine	Research Site	Zaporozhye

Sponsors (2)

Lead Sponsor	Collaborator
AstraZeneca	Bristol-Myers Squibb

Countries where clinical trial is conducted

Germany,  Hungary,  Romania,  Slovakia,  South Africa,  Switzerland,  Ukraine, 

References & Publications (1)

Schumm-Draeger PM, Burgess L, Korányi L, Hruba V, Hamer-Maansson JE, de Bruin TW. Twice-daily dapagliflozin co-administered with metformin in type 2 diabetes: a 16-week randomized, placebo-controlled clinical trial. Diabetes Obes Metab. 2015 Jan;17(1):42-51. doi: 10.1111/dom.12387. Epub 2014 Oct 16. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Adjusted Mean Change in HbA1c Levels	To compare the change from baseline in HbA1c achieved with each of the 2 BID doses of dapagliflozin (2.5 mg BID and 5 mg BID) co-administered with metformin versus placebo co-administered with metformin after 16 weeks of double-blind treatment.	Baseline to Week 16	No
Secondary	Adjusted Percent Change in Body Weight	To compare the percent change from baseline in body weight achieved with each of the 2 BID doses of dapagliflozin (2.5 mg BID, and 5 mg BID) co-administered with metformin versus placebo co-administered with metformin after 16 weeks of double-blind treatment.	Baseline to Week 16	No
Secondary	Adjusted Mean Change in Fasting Plasma Glucose (FPG) From Baseline to Week 1	To compare the change from baseline in fasting plasma glucose (FPG) achieved with each of the 2 BID doses of dapagliflozin (2.5 mg BID and 5 mg BID) co-administered with metformin versus placebo co-administered with metformin after 1 week of double-blind treatment.	Baseline to Week 1	No
Secondary	Adjusted Mean Change in Fasting Plasma Glucose (FPG) From Baseline to Week 16	To compare the change from baseline in fasting plasma glucose (FPG) achieved with each of the 2 BID doses of dapagliflozin (2.5 mg BID and 5 mg BID) co-administered with metformin versus placebo co-administered with metformin after 16 weeks of double-blind treatment.	Baseline to Week 16	No
Secondary	Proportion of Participants With HbA1c<7.0% at Week 16, in Participants Who Had HbA1c =7.0% at Baseline.	To compare the adjusted proportions controlling for baseline HbA1c [acc. to Zhang, Tsiatis & Davidian and Davidian, Tsiatis, Zhang & Lu] of participants with HbA1c <7.0% achieved with each of the 2 BID doses of dapagliflozin (2.5 mg BID and 5 mg BID) co-administered with metformin versus placebo co-administered with metformin after 16 weeks of double-blind treatment, in patients who had HbA1c =7.0% at baseline.	Baseline to Week 16	No

External Links

•   CSR-D1691C00003.pdf
•   D1691C00003_Clinical_Study_Protocol_Redacted