Type 2 DiabetesPhase 3NCT01217892

Evaluation of Dapagliflozin Taken Twice-daily

A Phase 3 study testing dapagliflozin and metformin in people with Type 2 Diabetes, run by AstraZeneca at 55 sites in 7 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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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. Read more about this study

Who is it for?: Ages 18 to 77 years
Conditions the study is for: Type 2 Diabetes
What is being tested?: dapagliflozin and metformin
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 400 participants
Where: 55 sitesin 7 countries
Study dates: Nov 2010to Aug 2011
Phase: Phase 3
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 77 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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.

Who cannot join

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

Trial locations and contacts

55 sites in 7 countries.

Country

City, postcode or hospital

55 sites in 7 countries

Germany11 sites

Research Site
Aßlar
Research Site
Berlin
Research Site
Biberach A.d. Riss
Research Site
Bosenheim
Research Site
Dippoldiswalde
Research Site
Falkensee
Research Site
Meissen
Research Site
München
Research Site
Neuwied
Research Site
Pirna
Research Site
Wahlstedt

Other trials in Germany

Slovakia11 sites

Research Site
Banská Bystrica
Research Site
Bratislava
Research Site
Dolný Kubín
Research Site
Košice
Research Site
Lučenec
Research Site
Námestovo
Research Site
Piešťany
Research Site
Prievidza
Research Site
Rimavská Sobota
Research Site
Ružomberok
Research Site
Žilina

Other trials in Slovakia

Hungary10 sites

Research Site
Balatonfüred
Research Site
Budapest
Research Site
Csongrád
Research Site
Debrecen
Research Site
Gyöngyös
Research Site
Kecskemét
Research Site
Makó
Research Site
Nyíregyháza
Research Site
Tát
Research Site
Zalaegerszeg

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Switzerland7 sites

Research Site
Basel
Research Site
Bern
Research Site
Chur, Kanton Graubünden
Research Site
Geneva
Research Site
Kreuzlingen
Research Site
Lugano
Research Site
Rorschach

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South Africa6 sites

Research Site
Cape Town, South Africa
Research Site
Durban, South Africa
Research Site
Durban
Research Site
eMkhomazi, South Africa
Research Site
Johannesburg, South Africa
Research Site
Verulam, KwaZulu-Natal

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Romania5 sites

Research Site
Brasov, Brașov County
Research Site
Bucharest
Research Site
Iași
Research Site
Sibiu
Research Site
Suceava

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Ukraine5 sites

Research Site
Dnipropetrov'sk
Research Site
Kiev
Research Site
Vinnytsia
Research Site
Vynnitsa, Ukraine
Research Site
Zaporizhzhya, Ukraine

Other trials in Ukraine

About this study

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

Conditions: Type 2 Diabetes
Being tested: dapagliflozin, metformin, placebo
Keywords: Type 2 diabetes, metformin treated, inadequate control, metformin treatment alone
Medical subject headings: Diabetes Mellitus, Type 2

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

dapagliflozinDrug
2.5 mg tablet, taken orally, twice daily
dapagliflozinDrug
5 mg tablet taken orally, twice daily
dapagliflozinDrug
10 mg tablet taken orally, once daily
metforminDrug
>/= 1500 mg total daily dose, tablets taken orally, twice daily
placeboDrug
placebo

Study groups in NCT01217892
Study group	Role	What they receive
1	Experimental	Dapagliflozin 2.5 mg twice-daily plus open-label metformin Receives: Drug: dapagliflozin; Drug: metformin
2	Experimental	Dapagliflozin 5.0 mg twice-daily plus open-label metformin Receives: Drug: dapagliflozin; Drug: metformin
3	Experimental	Dapagliflozin 10 mg once-daily plus open-label metformin Receives: Drug: dapagliflozin; Drug: metformin
4	Placebo comparator	Placebo plus open-label metformin Receives: Drug: metformin; Drug: placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: Baseline to Week 16

Secondary outcomes (4)

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.
Measured: Baseline to Week 16
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.
Measured: Baseline to Week 1
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.
Measured: Baseline to Week 16
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.
Measured: Baseline to Week 16

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Nov 2010Aug 2011

First posted8 Oct 2010 (estimated)
Study startNov 2010
Primary completionAug 2011
Study completionAug 2011

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Type 2 DiabetesStudies of the same condition, open and under way.
More trials run by AstraZenecaThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 3
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 400 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01217892
Sponsor's protocol ID: D1691C00003
Status last verified: Oct 2014
First submitted: 7 Oct 2010
Last updated: 27 Oct 2014
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Publications

Schumm-Draeger PM, Burgess L, Koranyi 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.
PubMed 25200570

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 27 Oct 2014. Recruitment status is as the sponsor reported it: confirm with the study team.

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
ClinicalTrials.gov ID: NCT01217892
Acronym / sponsor ID: D1691C00003
Conditions: Type 2 Diabetes
Keywords: Type 2 diabetes, metformin treated, inadequate control, metformin treatment alone
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 400 participants (actual)
Lead sponsor: AstraZenecaIndustry (pharma, biotech, devices)
Collaborators: Bristol-Myers Squibb
Study start: Nov 2010
Primary completion: Aug 2011 (actual)
Study completion: Aug 2011 (actual)
First posted: 8 Oct 2010 (estimated)
Results: Posted 1 Nov 2013

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 4

Arm	Type	Receives
1	Experimental	Drug: dapagliflozin, Drug: metforminDapagliflozin 2.5 mg twice-daily plus open-label metformin
2	Experimental	Drug: dapagliflozin, Drug: metforminDapagliflozin 5.0 mg twice-daily plus open-label metformin
3	Experimental	Drug: dapagliflozin, Drug: metforminDapagliflozin 10 mg once-daily plus open-label metformin
4	Placebo comparator	Drug: metformin, Drug: placeboPlacebo plus open-label metformin

Who may qualify

Ages: 18 to 77 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (4 listed)

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.

Key exclusion criteria (5 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
dapagliflozin2.5 mg tablet, taken orally, twice daily	Drug	1
dapagliflozin5 mg tablet taken orally, twice daily	Drug	2
dapagliflozin10 mg tablet taken orally, once daily	Drug	3
metformin>/= 1500 mg total daily dose, tablets taken orally, twice daily	Drug	1, 2, 3, 4
placeboplacebo	Drug	4

Primary outcome

Adjusted Mean Change in HbA1c Levels
Time frame: Baseline to Week 16
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.

4 secondary outcomes

Adjusted Percent Change in Body Weight
Time frame: Baseline to Week 16
Adjusted Mean Change in Fasting Plasma Glucose (FPG) From Baseline to Week 1
Time frame: Baseline to Week 1
Adjusted Mean Change in Fasting Plasma Glucose (FPG) From Baseline to Week 16
Time frame: Baseline to Week 16
Proportion of Participants With HbA1c<7.0% at Week 16, in Participants Who Had HbA1c ≥7.0% at Baseline.
Time frame: Baseline to Week 16

Results and safety

Results posted to the registry on 1 Nov 2013, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Dapagliflozin 2.5mg BID Plus Metformin	100	93
Dapagliflozin 5mg BID Plus Metformin	100	94
Dapagliflozin 10mg OD Plus Metformin	99	90
Placebo Plus Metformin	101	93

Primary outcome: Adjusted Mean Change in HbA1c Levels

Time frame: Baseline to Week 16. Least squares mean (Standard Error). Unit: Percent

Measure	Dapagliflozin 2.5mg BID Plus Metformin n = 99	Dapagliflozin 5mg BID Plus Metformin n = 97	Dapagliflozin 10mg OD Plus Metformin n = 98	Placebo Plus Metformin n = 100
Value	-0.52 (0.0594)	-0.65 (0.0600)	-0.59 (0.0598)	-0.30 (0.0593)

Dapagliflozin 2.5mg BID Plus Metformin vs Placebo Plus Metformin: Mean Difference (Final Values): -0.22 (95% CI -0.38 to -0.05), p = 0.0106, ANCOVA
Dapagliflozin 5mg BID Plus Metformin vs Placebo Plus Metformin: Mean Difference (Final Values): -0.35 (95% CI -0.52 to -0.18), p <0.0001, ANCOVA

Population analysed: Full Analysis Set, participants with non-missing baseline and Week 16 (LOCF) values

4 secondary outcomes are reported in the full results.

Adverse events

Time frame: Non-serious / serious adverse events on or after the first day and on or prior to the last day of the 16 weeks double-blind treatment period plus 4 days / 30 days or up to follow-up visit if earlier.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Dapagliflozin 2.5mg BID Plus Metformin	4 of 100 (4%)	8 of 100 (8%)	Not reported
Dapagliflozin 5mg BID Plus Metformin	1 of 100 (1%)	0 of 100 (0%)	Not reported
Dapagliflozin 10mg OD Plus Metformin	2 of 99 (2%)	6 of 99 (6.1%)	Not reported
Placebo Plus Metformin	0 of 101 (0%)	9 of 101 (8.9%)	Not reported

Limitations and caveats (from the sponsor): For participants who did not complete 16 weeks LOCF (last observation carried forward) was used.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 27 Oct 2014.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 25200570Schumm-Draeger PM, Burgess L, Koranyi 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.
CSR-D1691C00003.pdfLink provided by the sponsor.
D1691C00003\_Clinical\_Study\_Protocol\_RedactedLink provided by the sponsor.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Shamik Parikh study director

AstraZeneca

55 sites in 7 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing dapagliflozin and metformin in people with Type 2 Diabetes, run by AstraZeneca at 55 sites in 7 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 27 Oct 2014. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 55 sites in Germany, Slovakia, Hungary, Switzerland, South Africa and 2 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 1 Nov 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Adjusted Mean Change in HbA1c Levels (time frame: Baseline to Week 16). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01217892, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Oct 2014.