A Pilot Study of BMS-512148 in Subjects With Type 2 Diabetes

A Phase 2/3 study testing Dapagliflozin in people with Type 2 Diabetes, run by AstraZeneca at 23 sites in 2 countries.

Completed

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

Trial summary

The purpose of this clinical research study is to learn if BMS-512148, added to insulin and one or two anti-diabetes medications (metformin and/or pioglitazone or rosiglitazone), can help reduce the blood sugar levels compared to insulin and one or two anti-diabetes medications (metformin and/or pioglitazone or… Read more about this study

Who is it for?: Ages 18 to 75 years
Conditions the study is for: Type 2 Diabetes
What is being tested?: Dapagliflozin
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 163 participants
Where: 23 sitesin 2 countries
Study dates: Oct 2006to Mar 2008
Phase: Phase 2/3
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 75 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Males and females, 18 to 75 years old, with type 2 diabetes with inadequate glycemic control
Subjects receiving insulin and metformin and/or a thiazolidinedione
Body Mass Index <=45.0 kg/m2
Serum creatinine <1.5 mg/dL for men or <1.4 mg/dL for women
No overt proteinuria (in subjects with a microalbumin/creatinine ratio ≥300 mg/g, the 24-hour urinary excretion of total protein must be <3 g/24 hrs)

Who cannot join

History of type 1 diabetes
AST and/or ALT >2.5 times the upper limit of normal
Creatinine kinase ≥3 times the upper limit of normal
Symptoms of severely uncontrolled diabetes
History of hypoglycemic unawareness
Currently unstable or serious cardiovascular, renal, hepatic, hematological, oncological, endocrine, psychiatric, or rheumatic diseases

Trial locations and contacts

23 sites in 2 countries.

Country

City, postcode or hospital

23 sites in 2 countries

United States16 sites

University Of Michigan
Ann Arbor, Michigan, 48109
Mountain Diabetes And Endocrine Center
Asheville, North Carolina, 28801
Model Clinical Research Llc
Baltimore, Maryland, 21204
Research Institute Of Dallas, P.A.
Dallas, Texas, 75231
Valley Research
Fresno, California, 93720
Bernstein, Richard
Greenbrae, California, 94904
Indiana University
Indianapolis, Indiana, 46202
Jacksonville Center For Clinical Research
Jacksonville, Florida, 32205
Nea Clinic
Jonesboro, Arkansas, 72401
Your Diabetes Endocrine Nutrition Group
Mentor, Ohio, 44060
Advanced Healthcare S.C.
Milwaukee, Wisconsin, 53209
Rainier Clinical Research Center
Renton, Washington, 98055
Endocrine Research Solutions, Inc.
Roswell, Georgia, 30076
Diabetes And Glandular Disease Research Associates, P.A.
San Antonio, Texas, 78229
St. Louis Center For Clinical Research
St Louis, Missouri, 63128
Suny Upstate Medical University
Syracuse, New York, 13210

Other trials in United States

Canada7 sites

Local Institution
Bathurst, New Brunswick, E2A 4X7
Local Institution
Gatineau, Quebec, J8V 2P5
Local Institution
Laval, Quebec, H7T 2P5
Local Institution
Longueuil, Quebec, J4N 1L6
Local Institution
Pointe-Claire, Quebec, H9R 4S3
Local Institution
Sherbrooke, Quebec, J1G 5K2
Local Institution
Winnipeg, Manitoba, R3E 3P4

Other trials in Canada

About this study

Official title: A Pilot Study of the Efficacy and Safety of BMS-512148 on Glycemic Control in Subjects With Type 2 Diabetes Treated Aggressively But Not Controlled on Combination Antihyperglycemic Therapy With Metformin and/or Thiazolidinedione (TZD) and Insulin.

Conditions: Type 2 Diabetes
Being tested: Dapagliflozin, Placebo
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
Also called BMS-512148
Tablets, Oral, once daily, up to 12 weeks
PlaceboDrug
Tablets, Oral, 0 mg, once daily, up to 12 weeks

Study groups in NCT00357370
Study group	Role	What they receive
Cohort 1	Experimental	20 mg Receives: Drug: Dapagliflozin
Cohort 2 - Arm 1	Experimental	10 mg Receives: Drug: Dapagliflozin
Cohort 2 - Arm 2	Experimental	20 mg Receives: Drug: Dapagliflozin
Cohort 2 - Arm 3	Placebo comparator	Not described Receives: Drug: Placebo

What is being measured

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

Adjusted Mean Change From Baseline in Hemoglobin A1C (HbA1c) at Week 12 (Last Observation Carried Forward [LOCF]) - Cohort 2
HbA1c was measured as percent of hemoglobin by a central laboratory. Data after insulin uptitration was excluded from this analysis. Baseline was defined as the last assessment prior to the start date and time of the first dose of the double-blind study medication. In cases where time of the first dose or time of the assessment was not available, baseline was defined as the last assessment on or prior to the date of the first dose of the double-blind study medication. HbA1c measurements were obtained during the qualification and lead-in periods and on Day 1 and Weeks 4, 6, 8, 10, and 12 in the double-blind period.
Measured: From Baseline to Week 12

Secondary outcomes (5)

Adjusted Mean Change From Baseline in Fasting Plasma Glucose (FPG) at Week 12 (Last Observation Carried Forward [LOCF]) - Cohort 2
Fasting plasma glucose was measured as milligrams per deciliter(mg/dL) by a central laboratory. Data after insulin uptitration was excluded from this analysis. Baseline was defined as the last assessment prior to the start date and time of the first dose of the double-blind study medication. In cases where time of the first dose or time of the assessment was not available, baseline was defined as the last assessment on or prior to the date of the first dose of the double-blind study medication. FPG measurements were obtained during the qualification and lead-in periods and on Day 1 and Weeks 1, 2, 4, 6, 8, 10, and 12 in the double-blind period.
Measured: From Baseline to Week 12
Participants Achieving a Therapeutic Glycemic Response (Hemoglobin A1c [HbA1C]) <7.0% at Week 12 (Last Observation Carried Forward [LOCF]) - Cohort 2
Therapeutic glycemic response is defined as HbA1c <7.0%. Data after insulin uptitration was excluded from this analysis. HbA1c was measured as a percent of hemoglobin.
Measured: From Baseline to Week 12
Participants Achieving a Therapeutic Glycemic Response (Hemoglobin A1c [HbA1C]) <=6.5% at Week 12 (Last Observation Carried Forward [LOCF]) - Cohort 2
Therapeutic glycemic response is defined as HbA1c <=6.5%. Data after insulin uptitration was excluded from this analysis. HbA1c was measured as a percent of hemoglobin.
Measured: From Baseline to Week 12
Participants Achieving a Therapeutic Glycemic Response (Hemoglobin A1c [HbA1C]) Decrease From Baseline >= 0.5% at Week 12 (Last Observation Carried Forward [LOCF]) - Cohort 2
Therapeutic glycemic response is defined as HbA1c decrease from baseline >= 0.5% at Week 12. Data after insulin uptitration was excluded from this analysis. HbA1c was measured as a percent of hemoglobin.
Measured: From Baseline to Week 12
Adjusted Mean Total Daily Dose of Insulin (TDDI) Change From Baseline at Week 12 (LOCF), Including Data After Up-titration of Insulin) - Cohort 2
Baseline TDDI was reduced by 50% prior to treatment, except 2 subjects. TDDI could be up-titrated according to prespecified criteria at Weeks 4, 6, 8, 10 and 12 in the double-blind period.
Measured: From Baseline to Week 12

Timeline

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

Oct 2006Mar 2008

First posted27 Jul 2006 (estimated)
Study startOct 2006
Primary completionMar 2008
Study completionMar 2008

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 (3)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 2/3
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind
Who is masked: Participant, Investigator
Enrolment: 163 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00357370
Sponsor's protocol ID: MB102-009
Status last verified: Mar 2017
First submitted: 26 Jul 2006
Last updated: 11 May 2017
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Publications

Wilding JP, Norwood P, T'joen C, Bastien A, List JF, Fiedorek FT. A study of dapagliflozin in patients with type 2 diabetes receiving high doses of insulin plus insulin sensitizers: applicability of a novel insulin-independent treatment. Diabetes Care. 2009 Sep;32(9):1656-62. doi: 10.2337/dc09-0517. Epub 2009 Jun 15.
PubMed 19528367
Mellander A, Billger M, Johnsson E, Traff AK, Yoshida S, Johnsson K. Hypersensitivity Events, Including Potentially Hypersensitivity-Related Skin Events, with Dapagliflozin in Patients with Type 2 Diabetes Mellitus: A Pooled Analysis. Clin Drug Investig. 2016 Nov;36(11):925-933. doi: 10.1007/s40261-016-0438-3.
PubMed 27461213
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.
PubMed 26894924

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?

See locations

Active, not recruiting
Digital Reinforcement of Motivational Interviewing Micro-Skills Among Primary Care Healthcare Professionals
Hypertension (Without Type 2 Diabetes Mellitus)
Active, not recruitingObservational study
Family Investigation of Nephropathy and Diabetes (F.I.N.D.)
Diabetic Nephropathy, Diabetes Mellitus
Active, not recruitingPhase 4
Diabetes in African Youth
type1diabetes
Recruiting
Linking Education, Produce Provision, and Community Referrals to Improve Diabetes Care (LINK)
Diabetes Mellitus, Type 2, Nutrition Poor
Active, not recruitingObservational study
An Observational Study to Learn More About How Safe Finerenone is and How Well it Works in Indian People With Chronic Kidney Disease and Type 2 Diabetes in Routine Medical Practice
Chronic Kidney Disease, Type 2 Diabetes Mellitus

All Type 2 Diabetes trials

Study at a glance

From the registry record, last updated by the sponsor on 11 May 2017. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Pilot Study of the Efficacy and Safety of BMS-512148 on Glycemic Control in Subjects With Type 2 Diabetes Treated Aggressively But Not Controlled on Combination Antihyperglycemic Therapy With Metformin and/or Thiazolidinedione (TZD) and Insulin.
ClinicalTrials.gov ID: NCT00357370
Acronym / sponsor ID: MB102-009
Conditions: Type 2 Diabetes
Phase: Phase 2/3
Study type: Interventional
Recruitment status: Completed
Enrolment: 163 participants (actual)
Lead sponsor: AstraZenecaIndustry (pharma, biotech, devices)
Collaborators: Bristol-Myers Squibb
Study start: Oct 2006
Primary completion: Mar 2008 (actual)
Study completion: Mar 2008 (actual)
First posted: 27 Jul 2006 (estimated)
Results: Posted 11 May 2017

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: Double blind (participant, investigator)
Number of arms: 4

Arm	Type	Receives
Cohort 1	Experimental	Drug: Dapagliflozin20 mg
Cohort 2 - Arm 1	Experimental	Drug: Dapagliflozin10 mg
Cohort 2 - Arm 2	Experimental	Drug: Dapagliflozin20 mg
Cohort 2 - Arm 3	Placebo comparator	Drug: Placebo

Who may qualify

Ages: 18 to 75 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (5 listed)

Males and females, 18 to 75 years old, with type 2 diabetes with inadequate glycemic control
Subjects receiving insulin and metformin and/or a thiazolidinedione
Body Mass Index <=45.0 kg/m2
Serum creatinine <1.5 mg/dL for men or <1.4 mg/dL for women
No overt proteinuria (in subjects with a microalbumin/creatinine ratio ≥300 mg/g, the 24-hour urinary excretion of total protein must be <3 g/24 hrs)

Key exclusion criteria (6 listed)

History of type 1 diabetes
AST and/or ALT >2.5 times the upper limit of normal
Creatinine kinase ≥3 times the upper limit of normal
Symptoms of severely uncontrolled diabetes
History of hypoglycemic unawareness

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
DapagliflozinAlso: BMS-512148Tablets, Oral, once daily, up to 12 weeks	Drug	Cohort 1, Cohort 2 - Arm 1, Cohort 2 - Arm 2
PlaceboTablets, Oral, 0 mg, once daily, up to 12 weeks	Drug	Cohort 2 - Arm 3

Primary outcome

Adjusted Mean Change From Baseline in Hemoglobin A1C (HbA1c) at Week 12 (Last Observation Carried Forward [LOCF]) - Cohort 2
Time frame: From Baseline to Week 12
HbA1c was measured as percent of hemoglobin by a central laboratory. Data after insulin uptitration was excluded from this analysis. Baseline was defined as the last assessment prior to the start date and time of the first dose of the double-blind study medication. In cases where time of the first dose or time of the assessment was not available, baseline was defined as the last assessment on or prior to the date of the first dose of the double-blind study medication. HbA1c measurements were obtained during the qualification and lead-in periods and on Day 1 and Weeks 4, 6, 8, 10, and 12 in the double-blind period.

5 secondary outcomes

Adjusted Mean Change From Baseline in Fasting Plasma Glucose (FPG) at Week 12 (Last Observation Carried Forward [LOCF]) - Cohort 2
Time frame: From Baseline to Week 12
Participants Achieving a Therapeutic Glycemic Response (Hemoglobin A1c [HbA1C]) <7.0% at Week 12 (Last Observation Carried Forward [LOCF]) - Cohort 2
Time frame: From Baseline to Week 12
Participants Achieving a Therapeutic Glycemic Response (Hemoglobin A1c [HbA1C]) <=6.5% at Week 12 (Last Observation Carried Forward [LOCF]) - Cohort 2
Time frame: From Baseline to Week 12
Participants Achieving a Therapeutic Glycemic Response (Hemoglobin A1c [HbA1C]) Decrease From Baseline >= 0.5% at Week 12 (Last Observation Carried Forward [LOCF]) - Cohort 2
Time frame: From Baseline to Week 12
Adjusted Mean Total Daily Dose of Insulin (TDDI) Change From Baseline at Week 12 (LOCF), Including Data After Up-titration of Insulin) - Cohort 2
Time frame: From Baseline to Week 12

Results and safety

Results posted to the registry on 11 May 2017, 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 20 mg	4	4
Placebo	0	0
Dapagliflozin 10 mg	0	0

Primary outcome: Adjusted Mean Change From Baseline in Hemoglobin A1C (HbA1c) at Week 12 (Last Observation Carried Forward [LOCF]) - Cohort 2

Time frame: From Baseline to Week 12. Mean (Standard Error). Unit: % of hemoglobin

Measure	Placebo n = 19	Dapagliflozin 10 mg n = 23	Dapagliflozin 20 mg n = 23
Value	0.09 (0.1406)	-0.61 (0.1276)	-0.69 (0.1278)

Placebo vs Dapagliflozin 10 mg: Mean Difference (Final Values): -0.70 (95% CI -1.08 to -0.32)
Placebo vs Dapagliflozin 20 mg: Mean Difference (Final Values): -0.78 (95% CI -1.16 to -0.40)

Population analysed: Chort 2 all randomized participants who received study medication and had nonmissing HbA1c values at baseline and Week 12 (LOCF). Note: participants in cohort 1 provided data to establish an acceptable safety and tolerability profile when dapagliflozin 20 mg was added to open-label oral antidiabetic agent plus insulin.

5 secondary outcomes are reported in the full results.

Adverse events

Time frame: Onset on or after the first date of double-blind treatment and on or prior to the last day of double-blind treatment 12 weeks plus 4 days for non-serious adverse event; plus 30 days for serious adverse event.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Dapagliflozin 20 mg	1 of 24 (4.2%)	13 of 24 (54.2%)	Not reported
Placebo	1 of 23 (4.3%)	12 of 23 (52.2%)	Not reported
Dapagliflozin 10 mg	0 of 24 (0%)	12 of 24 (50%)	Not reported

Limitations and caveats (from the sponsor): Cohort 1 data provided information on insulin dose adjustment (n=4).

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 11 May 2017.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Results publication: PubMed 19528367Wilding JP, Norwood P, T'joen C, Bastien A, List JF, Fiedorek FT. A study of dapagliflozin in patients with type 2 diabetes receiving high doses of insulin plus insulin sensitizers: applicability of a novel insulin-independent treatment. Diabetes Care. 2009 Sep;32(9):1656-62. doi: 10.2337/dc09-0517. Epub 2009 Jun 15.
Derived from this study: PubMed 27461213Mellander A, Billger M, Johnsson E, Traff AK, Yoshida S, Johnsson K. Hypersensitivity Events, Including Potentially Hypersensitivity-Related Skin Events, with Dapagliflozin in Patients with Type 2 Diabetes Mellitus: A Pooled Analysis. Clin Drug Investig. 2016 Nov;36(11):925-933. doi: 10.1007/s40261-016-0438-3.
Derived from this study: PubMed 26894924Kohan 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.

Related trials for Type 2 Diabetes

Active, not recruiting
Digital Reinforcement of Motivational Interviewing Micro-Skills Among Primary Care Healthcare Professionals
Hypertension (Without Type 2 Diabetes Mellitus)
Active, not recruitingObservational study
Family Investigation of Nephropathy and Diabetes (F.I.N.D.)
Diabetic Nephropathy, Diabetes Mellitus
Active, not recruitingPhase 4
Diabetes in African Youth
type1diabetes
Recruiting
Linking Education, Produce Provision, and Community Referrals to Improve Diabetes Care (LINK)
Diabetes Mellitus, Type 2, Nutrition Poor
Active, not recruitingObservational study
An Observational Study to Learn More About How Safe Finerenone is and How Well it Works in Indian People With Chronic Kidney Disease and Type 2 Diabetes in Routine Medical Practice
Chronic Kidney Disease, Type 2 Diabetes Mellitus

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.

Bristol-Myers Squibb study director

Bristol-Myers Squibb

23 sites in 2 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2/3 study testing Dapagliflozin in people with Type 2 Diabetes, run by AstraZeneca at 23 sites in 2 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 5 inclusion and 6 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 11 May 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 23 sites in United States, Canada. 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 combined phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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 11 May 2017). 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 From Baseline in Hemoglobin A1C (HbA1c) at Week 12 (Last Observation Carried Forward [LOCF]) - Cohort 2 (time frame: From Baseline to Week 12). 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 NCT00357370, which also lists 3 linked publications.

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 11 May 2017; AzTrials last refreshed its copy on 6 Nov 2026.