## Protocol Section
### Identification Module
**NCT ID:** NCT00831779

**Brief Title:** Effects of Dapagliflozin on Insulin Resistance and Insulin Secretion in Subjects With Type 2 Diabetes

**Official Title:** A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Phase 2 Trial to Evaluate the Effects of Dapagliflozin on Insulin Resistance and Insulin Secretion in Subjects With Type 2 Diabetes

#### Organization Study ID Info
**ID:** MB102-045
#### Organization
**Class:** INDUSTRY
**Full Name:** AstraZeneca
### Status Module
#### Completion Date
**Date:** 2010-08

**Type:** ACTUAL

#### Disp First Post Date
**Date:** 2014-06-18

**Type:** ESTIMATED

**Disp First Submit Date:** 2012-03-24
**Disp First Submit QC Date:** 2014-06-06

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2017-04-24

**Type:** ACTUAL

**Last Update Submit Date:** 2017-03-24

**Overall Status:** COMPLETED

#### Primary Completion Date
**Date:** 2010-08

**Type:** ACTUAL

#### Results First Post Date
**Date:** 2017-03-01

**Type:** ACTUAL

**Results First Submit Date:** 2016-09-30

**Results First Submit QC Date:** 2017-01-10

#### Start Date
**Date:** 2009-04

**Status Verified Date:** 2017-03

#### Study First Post Date
**Date:** 2009-01-29
**Type:** ESTIMATED
**Study First Submit Date:** 2009-01-28
**Study First Submit QC Date:** 2009-01-28
### Sponsor Collaborators Module

#### Collaborators

**Class:** OTHER

**Name:** Astra Zeneca, Bristol-Myers Squibb

#### Lead Sponsor

**Class:** INDUSTRY

**Name:** AstraZeneca

#### Responsible Party

**Type:** SPONSOR

### Oversight Module

**Oversight Has DMC:** False

### Description Module

**Brief Summary:** The purpose of this study is to evaluate the effects of dapagliflozin on insulin sensitivity

### Conditions Module

**Conditions:**

- Type 2 Diabetes Mellitus

### Design Module

#### Design Info

**Allocation:** RANDOMIZED

**Intervention Model:** PARALLEL

##### Masking Info

**Masking:** QUADRUPLE

**Who Masked:**

- PARTICIPANT

- CARE_PROVIDER

- INVESTIGATOR

- OUTCOMES_ASSESSOR

**Primary Purpose:** TREATMENT

#### Enrollment Info

**Count:** 116

**Type:** ACTUAL

**Phases:**

- PHASE2

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Intervention Names:**

- Drug: Dapagliflozin

**Label:** Dapagliflozin

**Type:** EXPERIMENTAL

#### Arm Group 2

**Intervention Names:**

- Drug: Placebo

**Label:** Placebo

**Type:** PLACEBO_COMPARATOR

### Interventions

#### Intervention 1

**Arm Group Labels:**

- Dapagliflozin

**Description:** Tablets, Oral, 5 mg, once daily, 12 weeks

**Name:** Dapagliflozin

**Other Names:**

- BMS-512148

**Type:** DRUG

#### Intervention 2

**Arm Group Labels:**

- Placebo

**Description:** Tablets, Oral, 0 mg, Once daily, 12 weeks

**Name:** Placebo

**Type:** DRUG

### Outcomes Module

#### Primary Outcomes

**Description:** 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. Measurements were obtained during the randomization visit and Week 12 in the double-blind period.

**Measure:** Adjusted Mean Percent Change From Baseline in Insulin Sensitivity at Week 12 (Last Observation Carried Forward [LOCF])

**Time Frame:** From Baseline to Week 12

#### Secondary Outcomes

**Description:** 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. Measurements were obtained during the randomization visit and Week 12 in the double-blind period.

**Measure:** Adjusted Mean Change From Baseline in Insulin Secretion at Week 12 (Last Observation Carried Forward [LOCF])

**Time Frame:** From Baseline to Week 12

### Eligibility Module

**Eligibility Criteria:** Inclusion Criteria:

* Subjects with type 2 diabetes and inadequate glycemic control, defined as A1C ≥ 7.0 and ≤ 10.0% at the enrollment visit
* Subjects should have been receiving either metformin therapy OR metformin therapy AND one insulin secretagogue for at least 12 weeks prior to enrollment
* C-peptide ≥ 1.0 ng/ml (0.34 nmol/l)
* BMI ≤ 45.0 kg/m2

Exclusion Criteria:

* Urine albumin to creatinine ratio (UACR) \> 1,800 mg/g (203.4 mg/mmol/Cr)
* Aspartate Aminotransferase (AST) \> 3X Upper limit of normal (ULN)
* Alanine aminotransferase (ALT) \> 3X ULN
* Serum Total Bilirubin \> 2 mg/dL (34.2 μmol/l)
* Serum Creatinine (Scr) ≥ 1.50 mg/dL (133 μmol/l) for men; SCr ≥ 1.40 mg/dL (124 μmol/l) for women
* Currently unstable or serious cardiovascular, renal, hepatic, hematological, oncological, endocrine, psychiatric, or rheumatic diseases

**Maximum Age:** 70 Years

**Minimum Age:** 35 Years

**Sex:** ALL

**Standard Ages:**

- ADULT

- OLDER_ADULT

### Contacts Locations Module

#### Locations

**Location 1:**

**City:** San Diego

**Country:** United States

**Facility:** Va San Diego Healthcare System

**State:** California

**Zip:** 92161

**Location 2:**

**City:** Baton Rouge

**Country:** United States

**Facility:** Pennington Biomedical Research Center

**State:** Louisiana

**Zip:** 70808

**Location 3:**

**City:** Philadelphia

**Country:** United States

**Facility:** Temple University General Clinical Research Center

**State:** Pennsylvania

**Zip:** 19140

#### Overall Officials

**Official 1:**

**Affiliation:** Bristol-Myers Squibb

**Name:** Bristol-Myers Squibb

**Role:** STUDY_DIRECTOR

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000044882

- Term: Glucose Metabolism Disorders

- ID: D000008659

- Term: Metabolic Diseases

- ID: D000004700

- Term: Endocrine System Diseases

- ID: D000006946

- Term: Hyperinsulinism

### Condition Browse Module - Browse Branches

- Abbrev: BC18

- Name: Nutritional and Metabolic Diseases

- Abbrev: BC19

- Name: Gland and Hormone Related Diseases

- Abbrev: All

- Name: All Conditions

### Condition Browse Module - Browse Leaves

- ID: M7115

- Name: Diabetes Mellitus

- Relevance: HIGH

- As Found: Diabetes

- ID: M7119

- Name: Diabetes Mellitus, Type 2

- Relevance: HIGH

- As Found: Type 2 Diabetes

- ID: M10370

- Name: Insulin Resistance

- Relevance: HIGH

- As Found: Insulin Resistance

- ID: M11639

- Name: Metabolic Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M25403

- Name: Glucose Metabolism Disorders

- Relevance: LOW

- As Found: Unknown

- ID: M7862

- Name: Endocrine System Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M9997

- Name: Hyperinsulinism

- Relevance: LOW

- As Found: Unknown

### Condition Browse Module - Meshes

- ID: D000003920

- Term: Diabetes Mellitus

- ID: D000003924

- Term: Diabetes Mellitus, Type 2

- ID: D000007333

- Term: Insulin Resistance

### Intervention Browse Module - Ancestors

- ID: D000077203

- Term: Sodium-Glucose Transporter 2 Inhibitors

- ID: D000045504

- Term: Molecular Mechanisms of Pharmacological Action

- ID: D000007004

- Term: Hypoglycemic Agents

- ID: D000045505

- Term: Physiological Effects of Drugs

### Intervention Browse Module - Browse Branches

- Abbrev: Hypo

- Name: Hypoglycemic Agents

- Abbrev: All

- Name: All Drugs and Chemicals

### Intervention Browse Module - Browse Leaves

- ID: M10365

- Name: Insulin

- Relevance: LOW

- As Found: Unknown

- ID: M348449

- Name: Dapagliflozin

- Relevance: HIGH

- As Found: Intramuscular

- ID: M173166

- Name: Insulin, Globin Zinc

- Relevance: LOW

- As Found: Unknown

- ID: M1691

- Name: Sodium-Glucose Transporter 2 Inhibitors

- Relevance: LOW

- As Found: Unknown

- ID: M10054

- Name: Hypoglycemic Agents

- Relevance: LOW

- As Found: Unknown

### Intervention Browse Module - Meshes

- ID: C000529054

- Term: Dapagliflozin

### Misc Info Module

- Version Holder: 2024-05-24

## Results Section

### Adverse Events Module

#### Event Groups

**Group ID:** EG000

**Title:** Placebo + Background Anti-Diabetes Medication

**Description:** Placebo tablets, oral, once daily, 12 weeks

**ID:** EG000

**Other Num Affected:** 8

**Other Num at Risk:** 21

**Serious Number At Risk:** 21

**Title:** Placebo + Background Anti-Diabetes Medication

**Group ID:** EG001

**Title:** Dapagliflozin 5 mg + Background Anti-Diabetes Medication

**Description:** Dapagliflozin tablets, oral, once daily, 12 weeks

**ID:** EG001

**Other Num Affected:** 9

**Other Num at Risk:** 23

**Serious Number At Risk:** 23

**Title:** Dapagliflozin 5 mg + Background Anti-Diabetes Medication

**Frequency Threshold:** 5

#### Other Events

**Term:** HEADACHE

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Organ System:** Nervous system disorders

**Source Vocabulary:** MedDRA Version: 13.0

**Term:** INFUSION SITE PAIN

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Organ System:** General disorders

**Source Vocabulary:** MedDRA Version: 13.0

**Term:** MICTURITION URGENCY

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Organ System:** Renal and urinary disorders

**Source Vocabulary:** MedDRA Version: 13.0

**Term:** POLLAKIURIA

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Organ System:** Renal and urinary disorders

**Source Vocabulary:** MedDRA Version: 13.0

**Term:** URINARY TRACT INFECTION

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Organ System:** Infections and infestations

**Source Vocabulary:** MedDRA Version: 13.0

**Term:** OEDEMA PERIPHERAL

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Organ System:** General disorders

**Source Vocabulary:** MedDRA Version: 13.0

**Term:** SINUS CONGESTION

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Organ System:** Respiratory, thoracic and mediastinal disorders

**Source Vocabulary:** MedDRA Version: 13.0

**Term:** PYREXIA

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Organ System:** General disorders

**Source Vocabulary:** MedDRA Version: 13.0

**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.

## Results Section - Baseline Characteristics Module

### Denomination Counts

**Group ID:** BG000

**Value:** 21

**Group ID:** BG001

**Value:** 23

**Group ID:** BG002

**Value:** 44

**Units:** Participants

### Group

**ID:** BG000

**Title:** Placebo + Background Anti-Diabetes Medication

**Description:** Placebo tablets, oral, once daily, 12 weeks

### Group

**ID:** BG001

**Title:** Dapagliflozin 5 mg + Background Anti-Diabetes Medication

**Description:** Dapagliflozin tablets, oral, once daily, 12 weeks

### Group

**ID:** BG002

**Title:** Total

**Description:** Total of all reporting groups

### Measure

#### Measurement

**Group ID:** BG000

**Spread:** 8.02

**Value:** 53.3

#### Measurement

**Group ID:** BG001

**Spread:** 8.85

**Value:** 56.2

#### Measurement

**Group ID:** BG002

**Spread:** 8.49

**Value:** 54.8

**Class Title:** 

### Measure

#### Measurement

**Group ID:** BG000

**Value:** 18

#### Measurement

**Group ID:** BG001

**Value:** 19

#### Measurement

**Group ID:** BG002

**Value:** 37

**Class Title:** Younger than 65 years

#### Measurement

**Group ID:** BG000

**Value:** 3

#### Measurement

**Group ID:** BG001

**Value:** 4

#### Measurement

**Group ID:** BG002

**Value:** 7

**Class Title:** 65-70 years

### Measure

#### Measurement

**Group ID:** BG000

**Value:** 14

#### Measurement

**Group ID:** BG001

**Value:** 15

#### Measurement

**Group ID:** BG002

**Value:** 29

**Class Title:** Male

#### Measurement

**Group ID:** BG000

**Value:** 7

#### Measurement

**Group ID:** BG001

**Value:** 8

#### Measurement

**Group ID:** BG002

**Value:** 15

**Class Title:** Female

### Measure

#### Measurement

**Group ID:** BG000

**Value:** 15

#### Measurement

**Group ID:** BG001

**Value:** 13

#### Measurement

**Group ID:** BG002

**Value:** 28

**Class Title:** White

#### Measurement

**Group ID:** BG000

**Value:** 6

#### Measurement

**Group ID:** BG001

**Value:** 9

#### Measurement

**Group ID:** BG002

**Value:** 15

**Class Title:** Black/African American

#### Measurement

**Group ID:** BG000

**Value:** 0

#### Measurement

**Group ID:** BG001

**Value:** 1

#### Measurement

**Group ID:** BG002

**Value:** 1

**Class Title:** Asian

**Denomination Units Selected:** 

## Results Section - Baseline Characteristics Module

### Measure 1
**Dispersion Type:** STANDARD_DEVIATION
**Parameter Type:** MEAN
**Title:** Age, Continuous
**Unit of Measure:** Years
### Measure 2
**Parameter Type:** NUMBER
**Title:** Age, Customized
**Unit of Measure:** Participants
### Measure 3
**Parameter Type:** NUMBER
**Title:** Sex/Gender, Customized
**Unit of Measure:** Participants
### Measure 4
**Parameter Type:** NUMBER
**Title:** Race/Ethnicity, Customized
**Unit of Measure:** Participants
**Population Description:** All randomized participants who received at least 1 dose of study medication
## Results Section - More Information Module
### Certain Agreement
### Point of Contact
**Email:** ClinicalTrialTransparency@astrazeneca.com
**Organization:** AstraZeneca
**Title:** Anna Maria Langkilde
## Results Section - Outcome Measures Module
### Outcome Measure 1
#### Analysis
**CI Lower Limit:** 5.75
**CI Number of Sides:** TWO_SIDED
**CI Percentage Value:** 95
**CI Upper Limit:** 36.10
**CI Upper Limit Comment:** 
**Dispersion Type:** STANDARD_ERROR_OF_MEAN
**Dispersion Value:** 7.4685
**Estimate Comment:** 
**Group Description:** 
**Non-Inferiority Comment:** 
**Non-Inferiority Type:** SUPERIORITY_OR_OTHER
**Other Analysis Description:** 
**P-Value:** 0.0059
**P-Value Comment:** Primary endpoint was tested at alpha=0.05
**Parameter Type:** Mean Difference (Final Values)
**Parameter Value:** 19.97
**Statistical Comment:** 
**Statistical Method:** ANOVA
**Tested Non-Inferiority:** 
### Outcome Measure 2
#### Analysis
**CI Lower Limit:** -1.22
**CI Number of Sides:** TWO_SIDED
**CI Percentage Value:** 95
**CI Upper Limit:** 57.48
**CI Upper Limit Comment:** 
**Dispersion Type:** STANDARD_ERROR_OF_MEAN
**Dispersion Value:** 14.4984
**Estimate Comment:** 
**Group Description:** 
**Non-Inferiority Comment:** 
**Non-Inferiority Type:** SUPERIORITY_OR_OTHER
**Other Analysis Description:** 
**P-Value:** 0.0598
**P-Value Comment:** Secondary endpoint was tested following a sequential testing procedure at alpha=0.05
**Parameter Type:** Mean Difference (Final Values)
**Parameter Value:** 28.13
**Statistical Comment:** 
**Statistical Method:** ANOVA
**Tested Non-Inferiority:** 
## Results Section
### Outcome Measures Module
#### Outcome Measure 1
**Class:**
##### Category
**Measurements:**
- **Comment:** 
- **Group ID:** OG000
- **Lower Limit:** 
- **Spread:** 4.0392
- **Upper Limit:** 
- **Value:** -9.99
- **Comment:** 
- **Group ID:** OG001
- **Lower Limit:** 
- **Spread:** 4.4849
- **Upper Limit:** 
- **Value:** 7.98
**Title:** 
#### Outcome Measure 2
**Class:**
##### Category
**Measurements:**
- **Comment:** 
- **Group ID:** OG000
- **Lower Limit:** 
- **Spread:** 10.7107
- **Upper Limit:** 
- **Value:** -12.73
- **Comment:** 
- **Group ID:** OG001
- **Lower Limit:** 
- **Spread:** 9.5930
- **Upper Limit:** 
- **Value:** 15.39
**Title:** 
## Results Section
### Outcome Measures Module
#### Outcome Measure 1
**Description:** 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. Measurements were obtained during the randomization visit and Week 12 in the double-blind period.
**Dispersion Type:** Standard Error
**Parameter Type:** MEAN
**Population Description:** All randomized participants who received study medication and had nonmissing values at baseline and Week 12 (LOCF)
**Reporting Status:** POSTED
**Time Frame:** From Baseline to Week 12
**Title:** Adjusted Mean Percent Change From Baseline in Insulin Sensitivity at Week 12 (Last Observation Carried Forward [LOCF])
**Type:** PRIMARY
**Unit of Measure:** % Change of Baseline Insulin Sensitivity
##### Group
**Description:** Placebo tablets, oral, once daily, 12 weeks
**ID:** OG000
**Title:** Placebo + Background Anti-Diabetes Medication
##### Group
**Description:** Dapagliflozin tablets, oral, once daily, 12 weeks
**ID:** OG001
**Title:** Dapagliflozin 5 mg + Background Anti-Diabetes Medication
#### Outcome Measure 2
**Description:** 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. Measurements were obtained during the randomization visit and Week 12 in the double-blind period.
**Dispersion Type:** Standard Error
**Parameter Type:** MEAN
**Population Description:** All randomized participants who received study medication and had nonmissing values at baseline and Week 12 (LOCF)
**Reporting Status:** POSTED
**Time Frame:** From Baseline to Week 12
**Title:** Adjusted Mean Change From Baseline in Insulin Secretion at Week 12 (Last Observation Carried Forward [LOCF])
**Type:** SECONDARY
**Unit of Measure:** mU/L*min
##### Group
**Description:** Placebo tablets, oral, once daily, 12 weeks
**ID:** OG000
**Title:** Placebo + Background Anti-Diabetes Medication
##### Group
**Description:** Dapagliflozin tablets, oral, once daily, 12 weeks
**ID:** OG001
**Title:** Dapagliflozin 5 mg + Background Anti-Diabetes Medication
### Participant Flow Module
#### Group
**Description:** Placebo tablets, oral, once daily, 12 weeks
**ID:** FG000
**Title:** Placebo + Background Anti-Diabetes Medication
#### Group
**Description:** Dapagliflozin tablets, oral, once daily, 12 weeks
**ID:** FG001
**Title:** Dapagliflozin 5 mg + Background Anti-Diabetes Medication
#### Period
**Title:** Overall Study
##### Withdraw
**Type:** Lost to Follow-up
###### Reason
**Group ID:** FG000
**Number of Subjects:** 1
###### Reason
**Group ID:** FG001
**Number of Subjects:** 0
##### Withdraw
**Type:** No longer met criteria
###### Reason
**Group ID:** FG000
**Number of Subjects:** 0
###### Reason
**Group ID:** FG001
**Number of Subjects:** 1
##### Milestone
**Type:** STARTED
###### Achievement
**Group ID:** FG000
**Number of Subjects:** 21
###### Achievement
**Group ID:** FG001
**Number of Subjects:** 23
##### Milestone
**Type:** COMPLETED
###### Achievement
**Group ID:** FG000
**Number of Subjects:** 20
###### Achievement
**Group ID:** FG001
**Number of Subjects:** 22
##### Milestone
**Type:** NOT COMPLETED
###### Achievement
**Group ID:** FG000
**Number of Subjects:** 1
###### Achievement
**Group ID:** FG001
**Number of Subjects:** 1
**Recruitment Details:** Of 116 participants enrolled, 50 completed a qualification period. Of these 50 participants, 44 were randomized and received treatment. Of these 44 participants, 42 completed double-blind treatment period.
**Has Results:** True