Trial Outcomes & Findings for Add-on to Thiazolidinedione (TZD) Failures (NCT NCT00683878)

NCT ID: NCT00683878

Last Updated: 2017-02-23

Results Overview

HbA1c was measured as percent of hemoglobin by a central laboratory. Data after rescue medication 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, 8, 12, 16, 20, and 24 in the double-blind period.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 972 participants
• Primary outcome timeframe: From Baseline to Week 24
• Results posted on: 2017-02-23

Participant Flow

Of 972 participants enrolled, 558 completed a qualification period. Before entering lead-in period, 344 participants entered dose optimization period and 263 completed. A total of 480 participants entered the lead-in period, 420 randomized and received treatment, 367 completed double-blind treatment period.

Participant milestones

Measure	PLACEBO + Pioglitazone Placebo tablets, oral, once daily, up to 48 weeks plus pioglitazone tablets, ≥ 30 mg, once daily up to 48 weeks	Dapagliflozin 5MG + Pioglitazone Dapagliflozin tablets, oral, once daily, up to 48 weeks plus pioglitazone tablets, ≥ 30 mg, once daily up to 48 weeks	Dapagliflozin 10MG + Pioglitazone Dapagliflozin tablets, oral, once daily, up to 48 weeks plus pioglitazone tablets, ≥ 30 mg, once daily up to 48 weeks
Overall Study STARTED	139	141	140
Overall Study COMPLETED	116	125	126
Overall Study NOT COMPLETED	23	16	14

Reasons for withdrawal

Measure	PLACEBO + Pioglitazone Placebo tablets, oral, once daily, up to 48 weeks plus pioglitazone tablets, ≥ 30 mg, once daily up to 48 weeks	Dapagliflozin 5MG + Pioglitazone Dapagliflozin tablets, oral, once daily, up to 48 weeks plus pioglitazone tablets, ≥ 30 mg, once daily up to 48 weeks	Dapagliflozin 10MG + Pioglitazone Dapagliflozin tablets, oral, once daily, up to 48 weeks plus pioglitazone tablets, ≥ 30 mg, once daily up to 48 weeks
Overall Study Lack of Efficacy	3	0	1
Overall Study Adverse Event	4	3	3
Overall Study Withdrawal by Subject	9	8	6
Overall Study Death	0	1	0
Overall Study Lost to Follow-up	4	2	4
Overall Study Non-compliance, not met criteria etc.	3	2	0

Baseline Characteristics

Add-on to Thiazolidinedione (TZD) Failures

Baseline characteristics by cohort

Measure	PLACEBO + Pioglitazone n=139 Participants Placebo tablets, oral, once daily, up to 48 weeks plus pioglitazone tablets, ≥ 30 mg, once daily up to 48 weeks	Dapagliflozin 5MG + Pioglitazone n=141 Participants Dapagliflozin tablets, oral, once daily, up to 48 weeks plus pioglitazone tablets, ≥ 30 mg, once daily up to 48 weeks	Dapagliflozin 10MG + Pioglitazone n=140 Participants Dapagliflozin tablets, oral, once daily, up to 48 weeks plus pioglitazone tablets, ≥ 30 mg, once daily up to 48 weeks	Total n=420 Participants Total of all reporting groups
Age, Continuous	53.5 Years STANDARD_DEVIATION 11.38 • n=5 Participants	53.2 Years STANDARD_DEVIATION 10.90 • n=7 Participants	53.8 Years STANDARD_DEVIATION 10.35 • n=5 Participants	53.5 Years STANDARD_DEVIATION 10.86 • n=4 Participants
Age, Customized Yonger than 65 years	115 Participants n=5 Participants	120 Participants n=7 Participants	118 Participants n=5 Participants	353 Participants n=4 Participants
Age, Customized 65 to younger than 75 years	21 Participants n=5 Participants	16 Participants n=7 Participants	20 Participants n=5 Participants	57 Participants n=4 Participants
Age, Customized 75 years and older	3 Participants n=5 Participants	5 Participants n=7 Participants	2 Participants n=5 Participants	10 Participants n=4 Participants
Gender Female	68 Participants n=5 Participants	63 Participants n=7 Participants	81 Participants n=5 Participants	212 Participants n=4 Participants
Gender Male	71 Participants n=5 Participants	78 Participants n=7 Participants	59 Participants n=5 Participants	208 Participants n=4 Participants
Race/Ethnicity, Customized Asian	24 Participants n=5 Participants	26 Participants n=7 Participants	21 Participants n=5 Participants	71 Participants n=4 Participants
Race/Ethnicity, Customized Black/African American	6 Participants n=5 Participants	9 Participants n=7 Participants	7 Participants n=5 Participants	22 Participants n=4 Participants
Race/Ethnicity, Customized White	102 Participants n=5 Participants	102 Participants n=7 Participants	101 Participants n=5 Participants	305 Participants n=4 Participants
Race/Ethnicity, Customized Other	7 Participants n=5 Participants	4 Participants n=7 Participants	11 Participants n=5 Participants	22 Participants n=4 Participants

PRIMARY outcome

Timeframe: From Baseline to Week 24

Population: All randomized participants who received study medication and had nonmissing HbA1c values at baseline and Week 24 (LOCF)

HbA1c was measured as percent of hemoglobin by a central laboratory. Data after rescue medication 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, 8, 12, 16, 20, and 24 in the double-blind period.

Outcome measures

Measure	PLACEBO + Pioglitazone n=138 Participants Placebo tablets, oral, once daily, up to 48 weeks plus pioglitazone tablets, ≥ 30 mg, once daily up to 48 weeks	Dapagliflozin 5MG + Pioglitazone n=140 Participants Dapagliflozin tablets, oral, once daily, up to 48 weeks plus pioglitazone tablets, ≥ 30 mg, once daily up to 48 weeks	Dapagliflozin 10MG + Pioglitazone n=140 Participants Dapagliflozin tablets, oral, once daily, up to 48 weeks plus pioglitazone tablets, ≥ 30 mg, once daily up to 48 weeks
Adjusted Mean Change From Baseline in Hemoglobin A1C (HbA1c) at Week 24 (Last Observation Carried Forward [LOCF])	-0.42 % of hemoglobin Standard Error 0.0834	-0.82 % of hemoglobin Standard Error 0.0828	-0.97 % of hemoglobin Standard Error 0.0828

SECONDARY outcome

Timeframe: From Baseline to Week 24

Population: All randomized participants who received study medication and had nonmissing HbA1c values at baseline and Week 24 (LOCF)

Secondary endpoints were tested using sequential testing procedure and are presented in hierarchical order. In post oral glucose tolerance test (OGTT), glucose was measured as milligrams per deciliter(mg/dL) by a central laboratory. 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. PPG measurements were obtained on Day 1 and week 24 in the double-blind period.

Outcome measures

Measure	PLACEBO + Pioglitazone n=112 Participants Placebo tablets, oral, once daily, up to 48 weeks plus pioglitazone tablets, ≥ 30 mg, once daily up to 48 weeks	Dapagliflozin 5MG + Pioglitazone n=116 Participants Dapagliflozin tablets, oral, once daily, up to 48 weeks plus pioglitazone tablets, ≥ 30 mg, once daily up to 48 weeks	Dapagliflozin 10MG + Pioglitazone n=115 Participants Dapagliflozin tablets, oral, once daily, up to 48 weeks plus pioglitazone tablets, ≥ 30 mg, once daily up to 48 weeks
Adjusted Mean Change From Baseline in 120-minute Post-challenge Plasma Glucose (PPG) (mg/dL) at Week 24 (Last Observation Carried Forward [LOCF])	-14.1 mg/dL Standard Error 6.421	-65.1 mg/dL Standard Error 6.325	-67.5 mg/dL Standard Error 6.359

SECONDARY outcome

Timeframe: From Baseline to Week 24

Population: All randomized participants who received study medication and had nonmissing body weight values at baseline and Week 24 (LOCF)

Secondary endpoints were tested using sequential testing procedure and are presented in hierarchical order. Adjusted mean change from baseline in total body weight at Week 24 (or the last postbaseline measurement prior to Week 24 if no Week 24 assessment was available was determined. Data after rescue medication 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. Body weight measurements were obtained during the qualification and lead-in periods and on Day 1 and Weeks 1, 2, 4, 8, 12, 16, 20, and 24 of the double-blind period.

Outcome measures

Measure	PLACEBO + Pioglitazone n=139 Participants Placebo tablets, oral, once daily, up to 48 weeks plus pioglitazone tablets, ≥ 30 mg, once daily up to 48 weeks	Dapagliflozin 5MG + Pioglitazone n=140 Participants Dapagliflozin tablets, oral, once daily, up to 48 weeks plus pioglitazone tablets, ≥ 30 mg, once daily up to 48 weeks	Dapagliflozin 10MG + Pioglitazone n=140 Participants Dapagliflozin tablets, oral, once daily, up to 48 weeks plus pioglitazone tablets, ≥ 30 mg, once daily up to 48 weeks
Adjusted Mean Change From Baseline in Total Body Weight (kg) at Week 24 (Last Observation Carried Forward [LOCF])	1.64 kg Standard Error 0.2760	0.09 kg Standard Error 0.2752	-0.14 kg Standard Error 0.2753

SECONDARY outcome

Timeframe: From Baseline to Week 24

Population: All randomized participants who received study medication and had nonmissing FPG values at baseline and Week 24 (LOCF)

Secondary endpoints were tested using sequential testing procedure and are presented in hierarchical order. Fasting plasma glucose was measured as milligrams per deciliter(mg/dL) by a central laboratory. 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, 8, 12, 16, 20, and 24 in the double-blind period.

Outcome measures

Measure	PLACEBO + Pioglitazone n=139 Participants Placebo tablets, oral, once daily, up to 48 weeks plus pioglitazone tablets, ≥ 30 mg, once daily up to 48 weeks	Dapagliflozin 5MG + Pioglitazone n=140 Participants Dapagliflozin tablets, oral, once daily, up to 48 weeks plus pioglitazone tablets, ≥ 30 mg, once daily up to 48 weeks	Dapagliflozin 10MG + Pioglitazone n=140 Participants Dapagliflozin tablets, oral, once daily, up to 48 weeks plus pioglitazone tablets, ≥ 30 mg, once daily up to 48 weeks
Adjusted Mean Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24 (Last Observation Carried Forward [LOCF])	-5.5 mg/dL Standard Error 2.893	-24.9 mg/dL Standard Error 2.884	-29.6 mg/dL Standard Error 2.880

SECONDARY outcome

Timeframe: From Baseline to Week 24

Population: All randomized participants who received study medication and had nonmissing values at baseline and Week 24 (LOCF)

Secondary endpoints were tested using sequential testing procedure and are presented in hierarchical order. Percent adjusted for baseline HbA1c. Therapeutic glycemic response is defined as HbA1c <7.0%. Data after rescue medication was excluded from this analysis. HbA1c was measured as a percent of hemoglobin. Mean and standard error for percentage of participants were estimated by modified logistic regression model.

Outcome measures

Measure	PLACEBO + Pioglitazone n=138 Participants Placebo tablets, oral, once daily, up to 48 weeks plus pioglitazone tablets, ≥ 30 mg, once daily up to 48 weeks	Dapagliflozin 5MG + Pioglitazone n=140 Participants Dapagliflozin tablets, oral, once daily, up to 48 weeks plus pioglitazone tablets, ≥ 30 mg, once daily up to 48 weeks	Dapagliflozin 10MG + Pioglitazone n=140 Participants Dapagliflozin tablets, oral, once daily, up to 48 weeks plus pioglitazone tablets, ≥ 30 mg, once daily up to 48 weeks
Percentage of Participants Achieving a Therapeutic Glycemic Response (Hemoglobin A1c [HbA1C]) <7.0% at Week 24 (Last Observation Carried Forward [LOCF])	22.4 Percentage of participants Standard Error 3.276	32.5 Percentage of participants Standard Error 3.669	38.8 Percentage of participants Standard Error 3.835

SECONDARY outcome

Timeframe: From Baseline to Week 24

Population: All randomized participants who received study medication and had nonmissing waist circumference values at baseline and Week 24 (LOCF)

Secondary endpoints were tested using sequential testing procedure and are presented in hierarchical order. Adjusted mean change from baseline in waist circumference at Week 24 (or the last postbaseline measurement prior to Week 24 if no Week 24 assessment was available was determined. Data after rescue medication 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. Waist circumference measurements were obtained during the qualification and lead-in periods and on Day 1 and Week 24 of the double-blind period.

Outcome measures

Measure	PLACEBO + Pioglitazone n=126 Participants Placebo tablets, oral, once daily, up to 48 weeks plus pioglitazone tablets, ≥ 30 mg, once daily up to 48 weeks	Dapagliflozin 5MG + Pioglitazone n=132 Participants Dapagliflozin tablets, oral, once daily, up to 48 weeks plus pioglitazone tablets, ≥ 30 mg, once daily up to 48 weeks	Dapagliflozin 10MG + Pioglitazone n=133 Participants Dapagliflozin tablets, oral, once daily, up to 48 weeks plus pioglitazone tablets, ≥ 30 mg, once daily up to 48 weeks
Adjusted Mean Change From Baseline in Waist Circumference (cm) at Week 24 (Last Observation Carried Forward [LOCF])	1.38 cm Standard Error 0.4301	0.52 cm Standard Error 0.4198	-0.17 cm Standard Error 0.4182

SECONDARY outcome

Timeframe: From Baseline to Week 24

Population: All randomized participants who received study medication and had nonmissing body weight values at baseline and Week 24 (LOCF) among subjects with baseline body mass index (BMI) ≥ 27 kg/m\^2

Secondary endpoints were tested using sequential testing procedure and are presented in hierarchical order. Adjusted mean change from baseline in total body weight among subjects with baseline body mass index (BMI) ≥ 27 kg/m^2 at Week 24 (or the last postbaseline measurement prior to Week 24 if no Week 24 assessment was available was determined. Data after rescue medication 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. Body weight measurements were obtained during the qualification and lead-in periods and on Day 1 and Weeks 1, 2, 4, 8, 12, 16, 20, and 24 of the double-blind period.

Outcome measures

Measure	PLACEBO + Pioglitazone n=113 Participants Placebo tablets, oral, once daily, up to 48 weeks plus pioglitazone tablets, ≥ 30 mg, once daily up to 48 weeks	Dapagliflozin 5MG + Pioglitazone n=101 Participants Dapagliflozin tablets, oral, once daily, up to 48 weeks plus pioglitazone tablets, ≥ 30 mg, once daily up to 48 weeks	Dapagliflozin 10MG + Pioglitazone n=113 Participants Dapagliflozin tablets, oral, once daily, up to 48 weeks plus pioglitazone tablets, ≥ 30 mg, once daily up to 48 weeks
Adjusted Mean Change From Baseline in Total Body Weight (kg) Among Subjects With Baseline Body Mass Index (BMI) ≥ 27 kg/m^2 at Week 24 (Last Observation Carried Forward [LOCF])	1.83 kg Standard Error 0.3313	0.26 kg Standard Error 0.3523	-0.07 kg Standard Error 0.3332

Adverse Events

PLACEBO + Pioglitazone

Serious events: 1 serious events

Other events: 37 other events

Deaths: 0 deaths

Dapagliflozin 5MG + Pioglitazone

Serious events: 4 serious events

Other events: 34 other events

Deaths: 0 deaths

Dapagliflozin 10MG + Pioglitazone

Serious events: 2 serious events

Other events: 45 other events

Deaths: 0 deaths

Serious adverse events

Measure	PLACEBO + Pioglitazone n=139 participants at risk Placebo tablets, oral, once daily, up to 48 weeks plus pioglitazone tablets, ≥ 30 mg, once daily up to 48 weeks	Dapagliflozin 5MG + Pioglitazone n=141 participants at risk Dapagliflozin tablets, oral, once daily, up to 48 weeks plus pioglitazone tablets, ≥ 30 mg, once daily up to 48 weeks	Dapagliflozin 10MG + Pioglitazone n=140 participants at risk Dapagliflozin tablets, oral, once daily, up to 48 weeks plus pioglitazone tablets, ≥ 30 mg, once daily up to 48 weeks
Gastrointestinal disorders ABDOMINAL PAIN UPPER	0.00% 0/139 • Onset on or after the first date of double-blind treatment and on or prior to the last day of double-blind treatment 24 weeks plus 4 days for non-serious adverse event; plus 30 days for serious adverse event.	0.00% 0/141 • Onset on or after the first date of double-blind treatment and on or prior to the last day of double-blind treatment 24 weeks plus 4 days for non-serious adverse event; plus 30 days for serious adverse event.	0.71% 1/140 • Number of events 1 • Onset on or after the first date of double-blind treatment and on or prior to the last day of double-blind treatment 24 weeks plus 4 days for non-serious adverse event; plus 30 days for serious adverse event.
Investigations HEPATIC ENZYME INCREASED	0.00% 0/139 • Onset on or after the first date of double-blind treatment and on or prior to the last day of double-blind treatment 24 weeks plus 4 days for non-serious adverse event; plus 30 days for serious adverse event.	0.00% 0/141 • Onset on or after the first date of double-blind treatment and on or prior to the last day of double-blind treatment 24 weeks plus 4 days for non-serious adverse event; plus 30 days for serious adverse event.	0.71% 1/140 • Number of events 1 • Onset on or after the first date of double-blind treatment and on or prior to the last day of double-blind treatment 24 weeks plus 4 days for non-serious adverse event; plus 30 days for serious adverse event.
Musculoskeletal and connective tissue disorders PAIN IN EXTREMITY	0.00% 0/139 • Onset on or after the first date of double-blind treatment and on or prior to the last day of double-blind treatment 24 weeks plus 4 days for non-serious adverse event; plus 30 days for serious adverse event.	0.00% 0/141 • Onset on or after the first date of double-blind treatment and on or prior to the last day of double-blind treatment 24 weeks plus 4 days for non-serious adverse event; plus 30 days for serious adverse event.	0.71% 1/140 • Number of events 1 • Onset on or after the first date of double-blind treatment and on or prior to the last day of double-blind treatment 24 weeks plus 4 days for non-serious adverse event; plus 30 days for serious adverse event.
Cardiac disorders ACUTE MYOCARDIAL INFARCTION	0.00% 0/139 • Onset on or after the first date of double-blind treatment and on or prior to the last day of double-blind treatment 24 weeks plus 4 days for non-serious adverse event; plus 30 days for serious adverse event.	0.71% 1/141 • Number of events 1 • Onset on or after the first date of double-blind treatment and on or prior to the last day of double-blind treatment 24 weeks plus 4 days for non-serious adverse event; plus 30 days for serious adverse event.	0.00% 0/140 • Onset on or after the first date of double-blind treatment and on or prior to the last day of double-blind treatment 24 weeks plus 4 days for non-serious adverse event; plus 30 days for serious adverse event.
Cardiac disorders CORONARY ARTERY DISEASE	0.00% 0/139 • Onset on or after the first date of double-blind treatment and on or prior to the last day of double-blind treatment 24 weeks plus 4 days for non-serious adverse event; plus 30 days for serious adverse event.	0.71% 1/141 • Number of events 1 • Onset on or after the first date of double-blind treatment and on or prior to the last day of double-blind treatment 24 weeks plus 4 days for non-serious adverse event; plus 30 days for serious adverse event.	0.00% 0/140 • Onset on or after the first date of double-blind treatment and on or prior to the last day of double-blind treatment 24 weeks plus 4 days for non-serious adverse event; plus 30 days for serious adverse event.
General disorders NON-CARDIAC CHEST PAIN	0.72% 1/139 • Number of events 1 • Onset on or after the first date of double-blind treatment and on or prior to the last day of double-blind treatment 24 weeks plus 4 days for non-serious adverse event; plus 30 days for serious adverse event.	0.00% 0/141 • Onset on or after the first date of double-blind treatment and on or prior to the last day of double-blind treatment 24 weeks plus 4 days for non-serious adverse event; plus 30 days for serious adverse event.	0.00% 0/140 • Onset on or after the first date of double-blind treatment and on or prior to the last day of double-blind treatment 24 weeks plus 4 days for non-serious adverse event; plus 30 days for serious adverse event.
Hepatobiliary disorders CHOLECYSTITIS ACUTE	0.00% 0/139 • Onset on or after the first date of double-blind treatment and on or prior to the last day of double-blind treatment 24 weeks plus 4 days for non-serious adverse event; plus 30 days for serious adverse event.	0.71% 1/141 • Number of events 1 • Onset on or after the first date of double-blind treatment and on or prior to the last day of double-blind treatment 24 weeks plus 4 days for non-serious adverse event; plus 30 days for serious adverse event.	0.00% 0/140 • Onset on or after the first date of double-blind treatment and on or prior to the last day of double-blind treatment 24 weeks plus 4 days for non-serious adverse event; plus 30 days for serious adverse event.
Hepatobiliary disorders CHOLELITHIASIS	0.00% 0/139 • Onset on or after the first date of double-blind treatment and on or prior to the last day of double-blind treatment 24 weeks plus 4 days for non-serious adverse event; plus 30 days for serious adverse event.	0.71% 1/141 • Number of events 1 • Onset on or after the first date of double-blind treatment and on or prior to the last day of double-blind treatment 24 weeks plus 4 days for non-serious adverse event; plus 30 days for serious adverse event.	0.00% 0/140 • Onset on or after the first date of double-blind treatment and on or prior to the last day of double-blind treatment 24 weeks plus 4 days for non-serious adverse event; plus 30 days for serious adverse event.
Infections and infestations SEPTIC SHOCK	0.00% 0/139 • Onset on or after the first date of double-blind treatment and on or prior to the last day of double-blind treatment 24 weeks plus 4 days for non-serious adverse event; plus 30 days for serious adverse event.	0.71% 1/141 • Number of events 1 • Onset on or after the first date of double-blind treatment and on or prior to the last day of double-blind treatment 24 weeks plus 4 days for non-serious adverse event; plus 30 days for serious adverse event.	0.00% 0/140 • Onset on or after the first date of double-blind treatment and on or prior to the last day of double-blind treatment 24 weeks plus 4 days for non-serious adverse event; plus 30 days for serious adverse event.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) TRANSITIONAL CELL CARCINOMA	0.00% 0/139 • Onset on or after the first date of double-blind treatment and on or prior to the last day of double-blind treatment 24 weeks plus 4 days for non-serious adverse event; plus 30 days for serious adverse event.	0.71% 1/141 • Number of events 1 • Onset on or after the first date of double-blind treatment and on or prior to the last day of double-blind treatment 24 weeks plus 4 days for non-serious adverse event; plus 30 days for serious adverse event.	0.00% 0/140 • Onset on or after the first date of double-blind treatment and on or prior to the last day of double-blind treatment 24 weeks plus 4 days for non-serious adverse event; plus 30 days for serious adverse event.
Renal and urinary disorders NEPHROLITHIASIS	0.00% 0/139 • Onset on or after the first date of double-blind treatment and on or prior to the last day of double-blind treatment 24 weeks plus 4 days for non-serious adverse event; plus 30 days for serious adverse event.	0.71% 1/141 • Number of events 1 • Onset on or after the first date of double-blind treatment and on or prior to the last day of double-blind treatment 24 weeks plus 4 days for non-serious adverse event; plus 30 days for serious adverse event.	0.00% 0/140 • Onset on or after the first date of double-blind treatment and on or prior to the last day of double-blind treatment 24 weeks plus 4 days for non-serious adverse event; plus 30 days for serious adverse event.
Renal and urinary disorders RENAL COLIC	0.00% 0/139 • Onset on or after the first date of double-blind treatment and on or prior to the last day of double-blind treatment 24 weeks plus 4 days for non-serious adverse event; plus 30 days for serious adverse event.	0.71% 1/141 • Number of events 1 • Onset on or after the first date of double-blind treatment and on or prior to the last day of double-blind treatment 24 weeks plus 4 days for non-serious adverse event; plus 30 days for serious adverse event.	0.00% 0/140 • Onset on or after the first date of double-blind treatment and on or prior to the last day of double-blind treatment 24 weeks plus 4 days for non-serious adverse event; plus 30 days for serious adverse event.

Other adverse events

Measure	PLACEBO + Pioglitazone n=139 participants at risk Placebo tablets, oral, once daily, up to 48 weeks plus pioglitazone tablets, ≥ 30 mg, once daily up to 48 weeks	Dapagliflozin 5MG + Pioglitazone n=141 participants at risk Dapagliflozin tablets, oral, once daily, up to 48 weeks plus pioglitazone tablets, ≥ 30 mg, once daily up to 48 weeks	Dapagliflozin 10MG + Pioglitazone n=140 participants at risk Dapagliflozin tablets, oral, once daily, up to 48 weeks plus pioglitazone tablets, ≥ 30 mg, once daily up to 48 weeks
Metabolism and nutrition disorders DYSLIPIDAEMIA	4.3% 6/139 • Number of events 7 • Onset on or after the first date of double-blind treatment and on or prior to the last day of double-blind treatment 24 weeks plus 4 days for non-serious adverse event; plus 30 days for serious adverse event.	5.7% 8/141 • Number of events 8 • Onset on or after the first date of double-blind treatment and on or prior to the last day of double-blind treatment 24 weeks plus 4 days for non-serious adverse event; plus 30 days for serious adverse event.	9.3% 13/140 • Number of events 14 • Onset on or after the first date of double-blind treatment and on or prior to the last day of double-blind treatment 24 weeks plus 4 days for non-serious adverse event; plus 30 days for serious adverse event.
Infections and infestations NASOPHARYNGITIS	3.6% 5/139 • Number of events 7 • Onset on or after the first date of double-blind treatment and on or prior to the last day of double-blind treatment 24 weeks plus 4 days for non-serious adverse event; plus 30 days for serious adverse event.	5.0% 7/141 • Number of events 7 • Onset on or after the first date of double-blind treatment and on or prior to the last day of double-blind treatment 24 weeks plus 4 days for non-serious adverse event; plus 30 days for serious adverse event.	7.9% 11/140 • Number of events 11 • Onset on or after the first date of double-blind treatment and on or prior to the last day of double-blind treatment 24 weeks plus 4 days for non-serious adverse event; plus 30 days for serious adverse event.
Gastrointestinal disorders DIARRHOEA	4.3% 6/139 • Number of events 7 • Onset on or after the first date of double-blind treatment and on or prior to the last day of double-blind treatment 24 weeks plus 4 days for non-serious adverse event; plus 30 days for serious adverse event.	2.8% 4/141 • Number of events 4 • Onset on or after the first date of double-blind treatment and on or prior to the last day of double-blind treatment 24 weeks plus 4 days for non-serious adverse event; plus 30 days for serious adverse event.	6.4% 9/140 • Number of events 9 • Onset on or after the first date of double-blind treatment and on or prior to the last day of double-blind treatment 24 weeks plus 4 days for non-serious adverse event; plus 30 days for serious adverse event.
Musculoskeletal and connective tissue disorders BACK PAIN	1.4% 2/139 • Number of events 3 • Onset on or after the first date of double-blind treatment and on or prior to the last day of double-blind treatment 24 weeks plus 4 days for non-serious adverse event; plus 30 days for serious adverse event.	3.5% 5/141 • Number of events 5 • Onset on or after the first date of double-blind treatment and on or prior to the last day of double-blind treatment 24 weeks plus 4 days for non-serious adverse event; plus 30 days for serious adverse event.	5.0% 7/140 • Number of events 9 • Onset on or after the first date of double-blind treatment and on or prior to the last day of double-blind treatment 24 weeks plus 4 days for non-serious adverse event; plus 30 days for serious adverse event.
Infections and infestations UPPER RESPIRATORY TRACT INFECTION	5.8% 8/139 • Number of events 8 • Onset on or after the first date of double-blind treatment and on or prior to the last day of double-blind treatment 24 weeks plus 4 days for non-serious adverse event; plus 30 days for serious adverse event.	6.4% 9/141 • Number of events 11 • Onset on or after the first date of double-blind treatment and on or prior to the last day of double-blind treatment 24 weeks plus 4 days for non-serious adverse event; plus 30 days for serious adverse event.	5.0% 7/140 • Number of events 8 • Onset on or after the first date of double-blind treatment and on or prior to the last day of double-blind treatment 24 weeks plus 4 days for non-serious adverse event; plus 30 days for serious adverse event.
Nervous system disorders HEADACHE	6.5% 9/139 • Number of events 9 • Onset on or after the first date of double-blind treatment and on or prior to the last day of double-blind treatment 24 weeks plus 4 days for non-serious adverse event; plus 30 days for serious adverse event.	2.1% 3/141 • Number of events 4 • Onset on or after the first date of double-blind treatment and on or prior to the last day of double-blind treatment 24 weeks plus 4 days for non-serious adverse event; plus 30 days for serious adverse event.	2.9% 4/140 • Number of events 4 • Onset on or after the first date of double-blind treatment and on or prior to the last day of double-blind treatment 24 weeks plus 4 days for non-serious adverse event; plus 30 days for serious adverse event.
General disorders OEDEMA PERIPHERAL	5.0% 7/139 • Number of events 7 • Onset on or after the first date of double-blind treatment and on or prior to the last day of double-blind treatment 24 weeks plus 4 days for non-serious adverse event; plus 30 days for serious adverse event.	2.8% 4/141 • Number of events 4 • Onset on or after the first date of double-blind treatment and on or prior to the last day of double-blind treatment 24 weeks plus 4 days for non-serious adverse event; plus 30 days for serious adverse event.	2.1% 3/140 • Number of events 3 • Onset on or after the first date of double-blind treatment and on or prior to the last day of double-blind treatment 24 weeks plus 4 days for non-serious adverse event; plus 30 days for serious adverse event.

Additional Information

Anna Maria Langkilde

AstraZeneca

Email: ClinicalTrialTransparency@astrazeneca.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place