Efficacy and Safety of Dapagliflozin and Dapagliflozin Plus Saxagliptin in Combination With Metformin in Type 2 Diabetes Patients Compared With Sulphonylurea

Type 2 Diabetes Mellitus Clinical Trial

Official title:

A 52-Week, Multi-Centre, Randomised, Parallel-Group, Double-Blind, Active Controlled, Phase IV Study to Evaluate the Safety and Efficacy of Dapagliflozin or Dapagliflozin Plus Saxagliptin Compared With Sulphonylurea All Given as Add-on Therapy to Metformin in Adult Patients With Type 2 Diabetes Who Have Inadequate Glycaemic Control on Metformin Monotherapy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02471404
• Other study ID #: D1689C00014
• Status: Completed
• Phase: Phase 4
• Start date: September 21, 2015
• Est. completion date: March 13, 2017

Study information

• Verified date: March 2019
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study is being carried out to see if dapagliflozin and dapagliflozin plus saxagliptin as an addition to metformin is effective and safe in treating patients with type 2 diabetes when compared to glimepiride (sulphonylurea) as an addition to metformin treatment.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 939
• Est. completion date: March 13, 2017
• Est. primary completion date: March 13, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 74 Years

Eligibility

Inclusion Criteria: Main Inclusion Criteria:

1. Is male or female and =18 and <75 years old at time of informed consent.

2. Has a HbA1c of =7.5% and =10.5% based on central laboratory results from Visit 1, with individual need for therapy escalation.

3. Currently treated with a stable maximum tolarated dose (MTD) (=1500 mg/day) of metformin therapy for at least 8 weeks prior to Enrolment visit.

4. Has a BMI of =45 kg/m2 at Enrolment visit.

5. Has a C-peptide laboratory value of =1.0 ng/mL (0.33 nmol/L; 333.3 pmol/L) based on central laboratory results from Visit 1.

Main, Exclusion Criteria:

1. Clinically diagnosed with Type I diabetes, known diagnosis of maturity onset diabetes of the young (MODY), or secondary diabetes mellitus or known presence of glutamate decarboxylase 65 (GAD65) antibodies.

2. Patients who, in the judgment of the Investigator, may be at risk for dehydration or volume depletion that may affect the patient's safety and/or the interpretation of efficacy or safety data.

3. Clinically significant cardiovascular disease or procedure within 3 months prior to Enrolment or expected to require coronary revascularization procedure during the course of the study.

4. Concomitant treatment with loop diuretics

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Inadequate Glycaemic Control
• Type 2 Diabetes Mellitus

Intervention

Drug:
• Dapagliflozin
10 mg, orally Green, plain, diamond-shaped, film-coated tablet
• Saxagliptin
5 mg, orally Plain, yellow, biconvex, round, film-coated tablet
• Glimepiride
1, 2, or 4 mg, orally Opaque gray capsule
• Placebo for dapagliflozin
Does not contain active ingredient, orally Green, plain, diamond-shaped, film-coated tablet
• Placebo for saxagliptin
Does not contain active ingredient, orally Plain, yellow, biconvex, round, film-coated tablet
• Placebo for glimepiride
Does not contain active ingredient, orally. Opaque gray capsule

Locations

Country	Name	City	State
Czechia	Research Site	Hodonin
Czechia	Research Site	Hradec Kralove
Czechia	Research Site	Jilove u Prahy
Czechia	Research Site	Ostrava - Belsky les
Czechia	Research Site	Pardubice
Czechia	Research Site	Plzen - Severni Predmesti
Czechia	Research Site	Praha - Klanovice
Czechia	Research Site	Prelouc
Czechia	Research Site	Uherske Hradiste
Czechia	Research Site	Zlin
Germany	Research Site	Aschaffenburg
Germany	Research Site	Bad Homburg
Germany	Research Site	Bad Mergentheim
Germany	Research Site	Bad Nauheim
Germany	Research Site	Bad Neuenahr-Ahrweiler
Germany	Research Site	Bad Oeynhausen
Germany	Research Site	Bad Reichenhall
Germany	Research Site	Berlin
Germany	Research Site	Berlin
Germany	Research Site	Berlin
Germany	Research Site	Berlin
Germany	Research Site	Berlin
Germany	Research Site	Berlin
Germany	Research Site	Berlin
Germany	Research Site	Bochum
Germany	Research Site	Bochum
Germany	Research Site	Bonn
Germany	Research Site	Bünde
Germany	Research Site	Daaden
Germany	Research Site	Darmstadt
Germany	Research Site	Datteln
Germany	Research Site	Deggingen
Germany	Research Site	Dippoldiswalde
Germany	Research Site	Dortmund
Germany	Research Site	Dresden
Germany	Research Site	Duisburg
Germany	Research Site	Erfurt
Germany	Research Site	Erlangen
Germany	Research Site	Eschweiler
Germany	Research Site	Essen
Germany	Research Site	Essen
Germany	Research Site	Essen
Germany	Research Site	Frankfurt
Germany	Research Site	Frankfurt
Germany	Research Site	Frankfurt am Main
Germany	Research Site	Freiburg
Germany	Research Site	Freiburg im Breisgau
Germany	Research Site	Freudenstadt
Germany	Research Site	Gelnhausen
Germany	Research Site	Giengen
Germany	Research Site	Goch
Germany	Research Site	Göttingen
Germany	Research Site	Grevesmühlen
Germany	Research Site	Grossheirath
Germany	Research Site	Hamburg
Germany	Research Site	Hamburg
Germany	Research Site	Hamburg
Germany	Research Site	Hamburg
Germany	Research Site	Hamburg
Germany	Research Site	Hamburg
Germany	Research Site	Hameln
Germany	Research Site	Hannover
Germany	Research Site	Heidelberg
Germany	Research Site	Herne
Germany	Research Site	Hildesheim
Germany	Research Site	Hof
Germany	Research Site	Höhenkirchen
Germany	Research Site	Hohenmölsen
Germany	Research Site	Jerichow
Germany	Research Site	Kallstadt
Germany	Research Site	Karlsruhe
Germany	Research Site	Kassel
Germany	Research Site	Kiel-Kronshagen
Germany	Research Site	Köln
Germany	Research Site	Köthen
Germany	Research Site	Leipzig
Germany	Research Site	Leipzig
Germany	Research Site	Lichtenfels
Germany	Research Site	Lingen
Germany	Research Site	Löhne
Germany	Research Site	Ludwigshafen
Germany	Research Site	Magdeburg
Germany	Research Site	Mannheim
Germany	Research Site	Mannheim
Germany	Research Site	Marburg
Germany	Research Site	Marl
Germany	Research Site	Meine
Germany	Research Site	Meißen
Germany	Research Site	Mühldorf A. Inn
Germany	Research Site	München
Germany	Research Site	München
Germany	Research Site	München
Germany	Research Site	Münster
Germany	Research Site	Münster
Germany	Research Site	Neumünster
Germany	Research Site	Neuwied Am Rhein
Germany	Research Site	Oldenburg
Germany	Research Site	Papenburg
Germany	Research Site	Pirna
Germany	Research Site	Rehburg Loccum
Germany	Research Site	Rehlingen Siersburg
Germany	Research Site	Reinfeld
Germany	Research Site	Remagen
Germany	Research Site	Rhaunen
Germany	Research Site	Rodgau-Dudenhofen
Germany	Research Site	Saarlouis
Germany	Research Site	Schwabenheim
Germany	Research Site	Speyer
Germany	Research Site	Stadtbergen
Germany	Research Site	Stolberg
Germany	Research Site	Straubing
Germany	Research Site	Stuttgart
Germany	Research Site	Sulzbach
Germany	Research Site	Trier
Germany	Research Site	Villingen-Schwenningen
Germany	Research Site	Wahlstedt
Germany	Research Site	Wangen
Germany	Research Site	Weinheim
Germany	Research Site	Westerkappeln
Germany	Research Site	Wetzlar
Germany	Research Site	Witten
Hungary	Research Site	Ács
Hungary	Research Site	Budapest
Hungary	Research Site	Budapest
Hungary	Research Site	Budapest
Hungary	Research Site	Csongrád
Hungary	Research Site	Debrecen
Hungary	Research Site	Esztergom
Hungary	Research Site	Hatvan
Hungary	Research Site	Kisvárda
Hungary	Research Site	Komárom
Hungary	Research Site	Miskolc
Hungary	Research Site	Mosonmagyaróvár
Hungary	Research Site	Nyíregyháza
Hungary	Research Site	Orosháza-Szentetornya
Hungary	Research Site	Pécs
Hungary	Research Site	Polgár
Hungary	Research Site	Székesfehérvár
Poland	Research Site	Bochnia
Poland	Research Site	Bydgoszcz
Poland	Research Site	Chrzanow
Poland	Research Site	Gdansk
Poland	Research Site	Koluszki
Poland	Research Site	Krakow
Poland	Research Site	Legnica
Poland	Research Site	Lódz
Poland	Research Site	Mragowo
Poland	Research Site	Ostrowiec Swietokrzyski
Poland	Research Site	Poznan
Poland	Research Site	Sobótka
Poland	Research Site	Wierzchoslawice
Poland	Research Site	Wroclaw
Slovakia	Research Site	Banska Bystrica
Slovakia	Research Site	Bratislava
Slovakia	Research Site	Bratislava
Slovakia	Research Site	Kosice
Slovakia	Research Site	Kosice
Slovakia	Research Site	Kosice
Slovakia	Research Site	Levice
Slovakia	Research Site	Levice
Slovakia	Research Site	Lucenec
Slovakia	Research Site	Malacky
Slovakia	Research Site	Namestovo
Slovakia	Research Site	Nove Zamky
Slovakia	Research Site	Povazska Bystrica
Slovakia	Research Site	Povazska Bystrica
Slovakia	Research Site	Prievidza
Slovakia	Research Site	Puchov
Slovakia	Research Site	Rimavska Sobota
Slovakia	Research Site	Sabinov
Slovakia	Research Site	Trencin
Slovakia	Research Site	Trnava
Slovakia	Research Site	Vrutky

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Countries where clinical trial is conducted

Czechia,  Germany,  Hungary,  Poland,  Slovakia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Haemoglobin A1c (HbA1c) From Baseline to Week 52	Change in HbA1c from baseline (week 0) to week 52.	Baseline, week 52. Values recorded after rescue treatment or collected more than 8 days after the last dose date were excluded from the analysis
Secondary	Patients With at Least One Episode of Confirmed Hypoglycaemia	Percentage of patients reporting at least 1 episode of hypoglycaemia (symptomatic + blood glucose <=50 mg/dL) during the double-blind treatment period	Up to Week 52. Values recorded after rescue treatment or collected more than 8 days after the last dose date were excluded from the analysis
Secondary	Change in Total Body Weight From Baseline at Week 52	Change in body weight from baseline (week 0) to week 52	Baseline, week 52. Values recorded after rescue treatment or collected more than 8 days after the last dose date were excluded from the analysis
Secondary	Change in Fasting Plasma Glucose (FPG) From Baseline to Week 52	Change in FPG from baseline (week 0) to week 52	Baseline, week 52. Values recorded after rescue treatment or collected more than 8 days after the last dose date were excluded from the analysis
Secondary	Time to Rescue	The time to rescue (from first dose date after randomisation to start of rescue medication or discontinuation due to lack of glycaemic control) during the 52 week double blind treatment period	Over the 52 week treatment period
Secondary	Number of Patients Rescued	Number (%) of patients rescued.	Over the 52 week treatment period

External Links

•   d1689c00014_CSP_Redacted
•   d1689c00014_SAP_Redacted