Clinical Trials Register

Summary
EudraCT Number:	2010-019798-13
Sponsor's Protocol Code Number:	MB102-077
National Competent Authority:	Czechia - SUKL
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2011-03-29
Trial results	View results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Czechia - SUKL

A.2

EudraCT number

2010-019798-13

A.3

Full title of the trial

A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel Group, Phase 3 Trial to Evaluate the Safety and Efficacy of Dapagliflozin in Subjects with Type 2 Diabetes with Inadequately Controlled Hypertension treated with an Angiotensin-Converting Enzyme Inhibitor (ACEI) or Angiotensin Receptor Blocker
(ARB) and an Additional Antihypertensive Medication

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

A Trial to Evaluate the Safety and Efficacy of Dapagliflozin in Patients with Type 2 Diabetes with not very well controlled high blood pressure taking medicine called Angiotensin-Converting Enzyme Inhibitor (ACEI)
or Angiotensin Receptor Blocker (ARB) and Medication to reduce high Blood Preassure in addition. The Phase 3 Trial is carried out at several sites and neither patients nor doctors know which study treatment (medication in different strength or dummy treatment) they are assigned to.

A.4.1

Sponsor's protocol code number

MB102-077

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Bristol Myers Squibb International Corporation
B.1.3.4	Country	Belgium
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Bristol Myers Squibb International Corporation
B.4.2	Country	United States
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Bristol Myers Squibb International Corporation
B.5.2	Functional name of contact point	Karen Horry
B.5.3	Address:
B.5.3.1	Street Address	Chaussée de la Hulpe, 185
B.5.3.2	Town/ city	Brussels
B.5.3.3	Post code	1170
B.5.3.4	Country	Belgium
B.5.4	Telephone number	003223527305
B.5.5	Fax number	003223527294
B.5.6	E-mail	eu-su@bms.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Dapagliflozin
D.3.2	Product code	BMS-512148
D.3.4	Pharmaceutical form	Film-coated tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Dapagliflozin
D.3.9.2	Current sponsor code	BMS-512148
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	10
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Film-coated tablet
D.8.4	Route of administration of the placebo	Oral use
D.8 Placebo: 2
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Film-coated tablet
D.8.4	Route of administration of the placebo	Oral use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Type 2 diabetes with inadequate glycemic control and inadequately controlled hypertension

E.1.1.1

Medical condition in easily understood language

type 2 diabetes with not very well controlled blood sugar levels and not very well controlled high blood pressure

E.1.1.2

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	14.1
E.1.2	Level	PT
E.1.2	Classification code	10067585
E.1.2	Term	Type 2 diabetes mellitus
E.1.2	System Organ Class	10027433 - Metabolism and nutrition disorders

E.1.2 Medical condition or disease under investigation

E.1.2	Version	14.1
E.1.2	Level	LLT
E.1.2	Classification code	10066860
E.1.2	Term	Uncontrolled hypertension
E.1.2	System Organ Class	100000004866

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

• To compare the change from baseline in seated systolic blood pressure after 12
weeks of double-blind treatment with dapagliflozin 10 mg
treatment group versus placebo treatment group.
• To compare the change from baseline in HbA1c after 12 weeks of double-blind
treatment with dapagliflozin 10 mg treatment group versus placebo treatment group.

E.2.2

Secondary objectives of the trial

To compare the change from baseline in 24 hour ambulatory systolic blood
pressure after 12 weeks of double-blind treatment with dapagliflozin 10 mg treatment group and the placebo treatment group.
• To compare the change from baseline in seated and 24 hour ambulatory diastolic
blood pressure after 12 weeks of double-blind treatment with dapagliflozin 10 mg treatment group and the placebo treatment group.
• To compare the change from baseline in serum uric acid after 12 weeks of
double-blind treatment with dapagliflozin 10 mg treatment
group and the placebo treatment group.

E.2.3

Trial contains a sub-study

Yes

E.2.3.1

Full title, date and version of each sub-study and their related objectives

Pharmacogenetics Blood Sample Amendment-site specific: The objective of this Amendment is to permit the collection and storage of blood samples for use in future exploratory pharmacogenetic research. Bristol-Myers Squibb will use DNA obtained from the blood sample and health information collected from the main clinical trial, MB102077 to study the association between genetic variation and drug response. Bristol-Myers Squibb may also use the DNA to study the causes and further progression of Type 2 Diabetes and other Metabolic diseases. Samples from this study may also be used in conjunction with pharmacogenetic research results from other clinical studies to accomplish this objective.

E.3

Principal inclusion criteria

1) Subjects must be willing and able to give signed and dated written informed consent.
2) Subjects must have type 2 diabetes with inadequate glycemic control, defined as
central laboratory HbA1c ≥ 7.0% and ≤ 10.5% obtained at the enrollment visit.
Note: A one-time central laboratory re-test of the HbA1c is allowed in subjects with
an initial central laboratory HbA1c of 6.9% or 10.6% who are otherwise eligible, as
determined by the Investigator.
3) Subjects must be on a stable dose of an OAD for at least 6 weeks (12 weeks for a
TZD) or a stable daily dose of insulin, as a monotherapy or in combination with another OAD, for 8 weeks prior to enrollment, stable effective therapeutic dose of an ACEI or an ARB
and one additional antihypertensive medication (either a thiazide or thiazide-like
diuretic or a calcium channel blocker, beta blocker, central alpha adrenergic agonist
or alpha adrenergic blocker) for at least 4 weeks. Stable dose is defined as a dose that has remained the same for the specified number of weeks, as mentioned above, prior to the enrollment visit (ie, same prescribed total daily dose). Minimum effective therapeutic doses of all ACEI and ARB are defined in Appendix 5.
4) Subjects must have inadequately controlled hypertension, defined as seated SBP ≥ 140 and < 165 mmHg AND seated DBP ≥ 85 and < 105 mmHg, each representing the mean of three consecutive determinations, evaluated at both the enrollment and
Day 1 visits.
5) Subjects must have a mean 24-hour blood pressure ≥ 130/80 mmHg as determined by ambulatory blood pressure monitoring (ABPM) during lead in, measured between Day-7 and Day-1, within 1 week prior to the Day 1 randomization visit.
6) C-peptide ≥ 0.8 ng/mL (0.30 nmol/L).
7) BMI ≤ 45.0 kg/m2 at the enrollment visit.
8) Men and women ages must be ≥ 18 and ≤ 89 years old at the time of the enrollment visit. Men and women of childbearing potential (WOCBP) must be using an
acceptable method of contraception to avoid pregnancy throughout the study in such a manner that the risk of pregnancy is minimized. See Section 3.3.3 for the definition of WOCBP.
9) WOCBP must have a negative serum or urine pregnancy test (minimum sensitivity
25 IU/L or equivalent units of HCG) within 72 hours prior to the start of
investigational product.
10) Women must not be breastfeeding.

E.4

Principal exclusion criteria

1) History of diabetes insipidus
2) Symptoms of poorly controlled diabetes that would preclude participation in this trial
including, but not limited to, marked polyuria and polydipsia with greater than 10%
weight loss during the 3 months prior to enrollment, or other signs and symptoms.
3) History of diabetic ketoacidosis or hyperosmolar nonketotic coma.
4) History of malignant or accelerated hypertension.
5) Known or suspected secondary hypertension.
6) Myocardial infarction.
7) Cardiac surgery or revascularization (coronary artery bypass surgery [CABG]/
percutaneous transluminal coronary angioplasty [PTCA]).
8) Unstable angina.
9) Unstable congestive heart failure (CHF).
10) CHF New York Heart Association (NYHA) Class III or IV. (see Appendix 1)
11) Transient ischemic attack (TIA) or significant cerebrovascular disease.
12) Unstable or previously undiagnosed arrhythmia.
13) Under revised protocol #4 subjects with a History of Gout may be entered into the study
14) History of unstable or rapidly progressing renal disease.
15) Conditions of congenital renal glucosuria.
16) Renal allograft
17) Significant hepatic disease, including but not limited to, chronic active hepatitis
and/or severe hepatic insufficiency.
18) Documented history of hepatotoxicity with any medication.
19) Documented history of severe hepatobiliary disease.
20) History of hemoglobinopathy, with the exception of sickle cell trait (SA) or
thalassemia minor; or chronic or recurrent hemolysis.
21) Donation of blood or blood products to a blood bank, blood transfusion, or
participation in a clinical study requiring withdrawal of > 400 mL of blood during the
6 weeks prior to the enrollment visit.
22) Malignancy within 5 years of the enrollment visit (with the exception of treated basal
cell or treated squamous cell carcinoma of the skin).
23) Known immunocompromised status, including but not limited to, individuals who
have undergone organ transplantation or who are positive for the human
immunodeficiency virus.
24) Aspartate Aminotransferase (AST) > 3X Upper limit of normal (ULN).
25) Alanine aminotransferase (ALT) > 3X ULN.
26) Serum total bilirubin (TB) ≥ 1.5X ULN
27) Serum Creatinine (SCr) ≥ 2.0 mg/dL unless subject is on metformin then the
exclusionary limits will be SCr ≥ 1.50 mg/dL (133 μmol/L) for male subjects; SCr ≥
1.40 mg/dL (124 μmol/L) for female subjects
28) Estimated creatinine clearance (Crcl) of < 60ml/min
29) Hemoglobin ≤ 10.0 g/dL (100 g/L) for men; hemoglobin ≤ 9.0 g/dL (90 g/L) for
women.
30) Creatine kinase (CK) > 3X ULN.
31) Positive for hepatitis B surface antigen.
32) Positive for anti-hepatitis C virus antibody.
33) Abnormal free T4 value.
34) Allergies or contraindication to the contents of dapagliflozin tablets.
35) Obesity that would limit accurate blood pressure measurement
36) History of bariatric surgery or lap-band procedure.
37) Administration of sibutramine, phentermine, rimonabant, benzphetamine,
diethylpropion, methamphetamine, orlistat, and/or phendimetrazine.
38) Prisoners or subjects who are involuntarily incarcerated
39) Subjects who are compulsorily detained for treatment of either a psychiatric or
physical (eg, infectious disease) illness
40) Replacement or chronic systemic corticosteroid therapy, defined as any dose of
systemic corticosteroid taken for > 4 weeks within 3 months prior to enrollment visit.
41) Any unstable endocrine, psychiatric, rheumatic disorders as judged by the
Investigator.
42) Subject is, in the judgment of the Investigator, unlikely to comply with the protocol or
has any severe concurrent medical or psychological condition that may affect the
interpretation of efficacy or safety data.
43) Subject with any condition which, in the judgment of the Investigator, may render the
subject unable to complete the study or which may pose a significant risk to the
subject.
44) Subject is currently abusing alcohol or other drugs or has done so within the last
6 months.
45) Subject is a participating investigator, study coordinator, employee of an investigator
or immediate family member of any of the aforementioned.
46) Previous participation in a clinical trial with dapagliflozin (BMS-512148) and/or with
any other SGLT2 inhibitors.
47) Administration of any other investigational drug within 30 days of planned
enrollment to this study.

E.5 End points

E.5.1

Primary end point(s)

The co-primary endpoints are the change in seated systolic blood pressure from baseline at Week 12, or the last post-baseline measurement prior to Week 12 if no Week 12 assessment is available, and the change in HbA1c from baseline at Week 12, or the last post-baseline measurement prior to Week 12 if no Week 12 assessment is available.

E.5.1.1

Timepoint(s) of evaluation of this end point

at Week 12, or the last post-baseline measurement prior to Week 12 if no Week 12 assessment is available

E.5.2

Secondary end point(s)

N/A

E.5.2.1

Timepoint(s) of evaluation of this end point

N/A

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

Yes

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

E.7.3

Therapeutic confirmatory (Phase III)

Yes

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

Yes

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

Australia

Canada

Colombia

Czech Republic

Denmark

Finland

Germany

Hungary

India

Ireland

Mexico

Peru

Poland

United Kingdom

United States

E.8.7

Trial has a data monitoring committee

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

last patient's last visit

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1