Trial Outcomes & Findings for Glycemic Efficacy and Renal Safety Study of Dapagliflozin in Subjects With Type 2 Diabetes Mellitus and Moderate Renal Impairment (NCT NCT00663260)

Last Updated: 2017-02-10

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, 6, 8, 10, 12, 14, 16, 18, 20, 22, and 24 in the double-blind period.

Recruitment status

COMPLETED

Study phase

PHASE2/PHASE3

Target enrollment

631 participants

Primary outcome timeframe

From Baseline to Week 24

Results posted on

2017-02-10

Participant Flow

Of 631 participants enrolled, 276 completed a qualification period. Of these 276 participants, 252 were randomized and received treatment. Of these 252 participants, 204 completed double-blind treatment period.

Participant milestones

Participant milestones
Measure	Placebo Participants received dapagliflozin matching placebo once daily for up to 24 weeks (Subjects were to continue their original pre-enrollment anti-diabetic therapy; may include the addition of open-label anti-diabetic therapy as rescue)	Dapagliflozin 5 mg Participants received dapagliflozin 5 mg once daily for up to 24 weeks (Subjects were to continue their original pre-enrollment anti-diabetic therapy; may include the addition of open-label metformin as rescue)	Dapagliflozin 10 mg Participants received dapagliflozin 10 mg once daily for up to 24 weeks (Subjects were to continue their original pre-enrollment anti-diabetic therapy; may include the addition of open-label metformin as rescue)
Overall Study STARTED	84	83	85
Overall Study COMPLETED	63	72	69
Overall Study NOT COMPLETED	21	11	16

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Participants received dapagliflozin matching placebo once daily for up to 24 weeks (Subjects were to continue their original pre-enrollment anti-diabetic therapy; may include the addition of open-label anti-diabetic therapy as rescue)	Dapagliflozin 5 mg Participants received dapagliflozin 5 mg once daily for up to 24 weeks (Subjects were to continue their original pre-enrollment anti-diabetic therapy; may include the addition of open-label metformin as rescue)	Dapagliflozin 10 mg Participants received dapagliflozin 10 mg once daily for up to 24 weeks (Subjects were to continue their original pre-enrollment anti-diabetic therapy; may include the addition of open-label metformin as rescue)
Overall Study Lack of Efficacy	2	0	0
Overall Study Adverse Event	12	7	6
Overall Study Withdrawal by Subject	3	1	6
Overall Study Death	1	0	1
Overall Study Lost to Follow-up	0	1	0
Overall Study non-compliance, not met criteria, etc.	3	2	3

Baseline Characteristics

Glycemic Efficacy and Renal Safety Study of Dapagliflozin in Subjects With Type 2 Diabetes Mellitus and Moderate Renal Impairment

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=84 Participants Participants received dapagliflozin matching placebo once daily for up to 24 weeks (Subjects were to continue their original pre-enrollment anti-diabetic therapy; may include the addition of open-label anti-diabetic therapy as rescue)	Dapagliflozin 5 mg n=83 Participants Participants received dapagliflozin 5 mg once daily for up to 24 weeks (Subjects were to continue their original pre-enrollment anti-diabetic therapy; may include the addition of open-label metformin as rescue)	Dapagliflozin 10 mg n=85 Participants Participants received dapagliflozin 10 mg once daily for up to 24 weeks (Subjects were to continue their original pre-enrollment anti-diabetic therapy; may include the addition of open-label metformin as rescue)	Total n=252 Participants Total of all reporting groups
Age, Continuous	67 Years STANDARD_DEVIATION 8.6 • n=5 Participants	66 Years STANDARD_DEVIATION 8.9 • n=7 Participants	68 Years STANDARD_DEVIATION 7.7 • n=5 Participants	67 Years STANDARD_DEVIATION 8.4 • n=4 Participants
Age, Customized Younger than 65 years	36 Participants n=5 Participants	39 Participants n=7 Participants	29 Participants n=5 Participants	104 Participants n=4 Participants
Age, Customized 65 years and older	48 Participants n=5 Participants	44 Participants n=7 Participants	56 Participants n=5 Participants	148 Participants n=4 Participants
Sex/Gender, Customized Male	53 Participants n=5 Participants	55 Participants n=7 Participants	56 Participants n=5 Participants	164 Participants n=4 Participants
Sex/Gender, Customized Female	31 Participants n=5 Participants	28 Participants n=7 Participants	29 Participants n=5 Participants	88 Participants n=4 Participants
Race/Ethnicity, Customized WHITE	69 Participants n=5 Participants	65 Participants n=7 Participants	77 Participants n=5 Participants	211 Participants n=4 Participants
Race/Ethnicity, Customized BLACK OR AFRICAN AMERICAN	1 Participants n=5 Participants	7 Participants n=7 Participants	4 Participants n=5 Participants	12 Participants n=4 Participants
Race/Ethnicity, Customized ASIAN	6 Participants n=5 Participants	4 Participants n=7 Participants	3 Participants n=5 Participants	13 Participants n=4 Participants
Race/Ethnicity, Customized OTHER	8 Participants n=5 Participants	7 Participants n=7 Participants	1 Participants n=5 Participants	16 Participants n=4 Participants
Weight	89.61 kg STANDARD_DEVIATION 20.046 • n=5 Participants	95.23 kg STANDARD_DEVIATION 20.909 • n=7 Participants	93.25 kg STANDARD_DEVIATION 17.309 • n=5 Participants	92.69 kg STANDARD_DEVIATION 19.529 • n=4 Participants
Pre-Enrollment Anti-Hyperglycemic Therapy INSULIN-BASED REGIMEN	55 Participants n=5 Participants	54 Participants n=7 Participants	55 Participants n=5 Participants	164 Participants n=4 Participants
Pre-Enrollment Anti-Hyperglycemic Therapy SULFONYLUREA-BASED REGIMEN	21 Participants n=5 Participants	21 Participants n=7 Participants	21 Participants n=5 Participants	63 Participants n=4 Participants
Pre-Enrollment Anti-Hyperglycemic Therapy THIAZOLIINEDIONE-BASED REGIMEN	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants	4 Participants n=4 Participants
Pre-Enrollment Anti-Hyperglycemic Therapy OTHER REGIMEN	7 Participants n=5 Participants	7 Participants n=7 Participants	7 Participants n=5 Participants	21 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)

Outcome measures

Outcome measures
Measure	Placebo n=82 Participants Participants received dapagliflozin matching placebo once daily for up to 24 weeks (Subjects were to continue their original pre-enrollment anti-diabetic therapy; may include the addition of open-label anti-diabetic therapy as rescue)	Dapagliflozin 5 mg n=83 Participants Participants received dapagliflozin 5 mg once daily for up to 24 weeks (Subjects were to continue their original pre-enrollment anti-diabetic therapy; may include the addition of open-label metformin as rescue)	Dapagliflozin 10 mg n=82 Participants Participants received dapagliflozin 10 mg once daily for up to 24 weeks (Subjects were to continue their original pre-enrollment anti-diabetic therapy; may include the addition of open-label metformin as rescue)
Adjusted Mean Change From Baseline in Hemoglobin A1C (HbA1c) at Week 24 (Last Observation Carried Forward [LOCF]	-0.32 % of hemoglobin Standard Error 0.1701	-0.41 % of hemoglobin Standard Error 0.1701	-0.44 % of hemoglobin Standard Error 0.1708

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, 6, 8, 10, 12, 14, 16, 18, 20, 22, and 24 in the double-blind period

Outcome measures

Outcome measures
Measure	Placebo n=83 Participants Participants received dapagliflozin matching placebo once daily for up to 24 weeks (Subjects were to continue their original pre-enrollment anti-diabetic therapy; may include the addition of open-label anti-diabetic therapy as rescue)	Dapagliflozin 5 mg n=83 Participants Participants received dapagliflozin 5 mg once daily for up to 24 weeks (Subjects were to continue their original pre-enrollment anti-diabetic therapy; may include the addition of open-label metformin as rescue)	Dapagliflozin 10 mg n=85 Participants Participants received dapagliflozin 10 mg once daily for up to 24 weeks (Subjects were to continue their original pre-enrollment anti-diabetic therapy; may include the addition of open-label metformin as rescue)
Adjusted Mean Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24 (Last Observation Carried Forward [LOCF])	8.4 mg/dL Standard Error 9.621	-5.2 mg/dL Standard Error 9.548	-0.6 mg/dL Standard Error 9.524

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

Outcome measures
Measure	Placebo n=84 Participants Participants received dapagliflozin matching placebo once daily for up to 24 weeks (Subjects were to continue their original pre-enrollment anti-diabetic therapy; may include the addition of open-label anti-diabetic therapy as rescue)	Dapagliflozin 5 mg n=83 Participants Participants received dapagliflozin 5 mg once daily for up to 24 weeks (Subjects were to continue their original pre-enrollment anti-diabetic therapy; may include the addition of open-label metformin as rescue)	Dapagliflozin 10 mg n=85 Participants Participants received dapagliflozin 10 mg once daily for up to 24 weeks (Subjects were to continue their original pre-enrollment anti-diabetic therapy; may include the addition of open-label metformin as rescue)
Adjusted Mean Change From Baseline in Total Body Weight (kg) at Week 24 (Last Observation Carried Forward [LOCF])	0.27 kg Standard Error 0.4872	-1.54 kg Standard Error 0.4815	-1.89 kg Standard Error 0.4693

Adverse Events

Placebo

Serious events: 9 serious events

Other events: 39 other events

Deaths: 0 deaths

Dapagliflozin 5 mg

Serious events: 7 serious events

Other events: 45 other events

Deaths: 0 deaths

Dapagliflozin 10 mg

Serious events: 12 serious events

Other events: 42 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Anna Maria Langkilde

AstraZeneca

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Placebo n=84 participants at risk Participants received dapagliflozin matching placebo once daily for up to 24 weeks (Subjects were to continue their original pre-enrollment anti-diabetic therapy; may include the addition of open-label anti-diabetic therapy as rescue)	Dapagliflozin 5 mg n=83 participants at risk Participants received dapagliflozin 5 mg once daily for up to 24 weeks (Subjects were to continue their original pre-enrollment anti-diabetic therapy; may include the addition of open-label metformin as rescue)	Dapagliflozin 10 mg n=85 participants at risk Participants received dapagliflozin 10 mg once daily for up to 24 weeks (Subjects were to continue their original pre-enrollment anti-diabetic therapy; may include the addition of open-label metformin as rescue)
Renal and urinary disorders POLLAKIURIA	3.6% 3/84 • 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.	6.0% 5/83 • 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.	11.8% 10/85 • Number of events 12 • 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.
Respiratory, thoracic and mediastinal disorders COUGH	2.4% 2/84 • 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.	9.6% 8/83 • 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.	9.4% 8/85 • Number of events 10 • 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	3.6% 3/84 • 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.	3.6% 3/83 • 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.	9.4% 8/85 • 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 MUSCULOSKELETAL PAIN	3.6% 3/84 • 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.	3.6% 3/83 • 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.	8.2% 7/85 • 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.
Gastrointestinal disorders NAUSEA	1.2% 1/84 • 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.	3.6% 3/83 • 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.	8.2% 7/85 • 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.
Infections and infestations UPPER RESPIRATORY TRACT INFECTION	3.6% 3/84 • 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.	3.6% 3/83 • 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.	7.1% 6/85 • 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.
Nervous system disorders DIZZINESS	4.8% 4/84 • 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.	12.0% 10/83 • 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.	5.9% 5/85 • 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.
Metabolism and nutrition disorders HYPERKALAEMIA	11.9% 10/84 • Number of events 16 • 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.	8.4% 7/83 • 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.	5.9% 5/85 • Number of events 6 • 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.
Vascular disorders HYPERTENSION	6.0% 5/84 • Number of events 6 • 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.	1.2% 1/83 • 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.	5.9% 5/85 • 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.
Infections and infestations NASOPHARYNGITIS	6.0% 5/84 • 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.	7.2% 6/83 • Number of events 6 • 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.	4.7% 4/85 • 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.
General disorders OEDEMA PERIPHERAL	4.8% 4/84 • 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.	9.6% 8/83 • Number of events 10 • 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.	4.7% 4/85 • Number of events 6 • 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 ARTHRALGIA	6.0% 5/84 • Number of events 6 • 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.	6.0% 5/83 • 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.	2.4% 2/85 • Number of events 2 • 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	7.1% 6/84 • 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.	8.4% 7/83 • 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.	2.4% 2/85 • Number of events 2 • 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 MICTURITION URGENCY	0.00% 0/84 • 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.	6.0% 5/83 • 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.	2.4% 2/85 • 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.
Infections and infestations GASTROENTERITIS	6.0% 5/84 • Number of events 6 • 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.	1.2% 1/83 • 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.	1.2% 1/85 • 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.