Trial Outcomes & Findings for Evaluate the Efficacy and Safety of Saxagliptin in Combination With Metformin IR Compared to Saxagliptin Monotherapy and to Metformin IR Monotherapy in Drug Naive Chinese Subjects With Type 2 Diabetes Who Have Inadequate Glycaemic Control (NCT NCT02273050)

Last Updated: 2018-02-05

Results Overview

To evaluate the efficacy of the combination therapy (saxagliptin + metformin) when compared to placebo + metformin and placebo + saxagliptin with respect to reduction in HbA1c (%) at the end of 24 weeks of double-blinded treatment.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

1136 participants

Primary outcome timeframe

Baseline to Week 24 (prior to rescue)

Results posted on

2018-02-05

Participant Flow

The study was conducted in 25 centers between 18 December 2014 and 03 August 2016.

The study duration was up to 27 weeks, consisting of an initial screening period lasting up to 2 weeks, a 1-week lead-in period, and a 24-week treatment period. The number of subjects who signed the ICF is 1136, the number of subjects randomized is 640.

Participant milestones

Participant milestones
Measure	METFORMIN + PLACEBO 5MG QD	SAXAGLIPTIN 5MG QD + METFORMIN	SAXAGLIPTIN 5MG QD + PLACEBO
Overall Study STARTED	210	216	214
Overall Study COMPLETED	186	194	185
Overall Study NOT COMPLETED	24	22	29

Reasons for withdrawal

Reasons for withdrawal
Measure	METFORMIN + PLACEBO 5MG QD	SAXAGLIPTIN 5MG QD + METFORMIN	SAXAGLIPTIN 5MG QD + PLACEBO
Overall Study Adverse Event	4	3	3
Overall Study Death	0	0	1
Overall Study Dev. of study spec. withdrawal criteria	0	1	1
Overall Study Lack of Efficacy	0	1	1
Overall Study Withdrawal by Subject	17	14	16
Overall Study Lost to Follow-up	0	2	3
Overall Study Protocol Violation	3	1	4

Baseline Characteristics

Evaluate the Efficacy and Safety of Saxagliptin in Combination With Metformin IR Compared to Saxagliptin Monotherapy and to Metformin IR Monotherapy in Drug Naive Chinese Subjects With Type 2 Diabetes Who Have Inadequate Glycaemic Control

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	METFORMIN + PLACEBO 5MG QD n=210 Participants	SAXAGLIPTIN 5MG QD + METFORMIN n=216 Participants	SAXAGLIPTIN 5MG QD + PLACEBO n=214 Participants	Total n=640 Participants Total of all reporting groups
Age, Continuous	50.1 Years STANDARD_DEVIATION 11.08 • n=5 Participants	50.4 Years STANDARD_DEVIATION 10.78 • n=7 Participants	49.5 Years STANDARD_DEVIATION 10.93 • n=5 Participants	50.0 Years STANDARD_DEVIATION 10.92 • n=4 Participants
Sex: Female, Male Female	76 Participants n=5 Participants	76 Participants n=7 Participants	62 Participants n=5 Participants	214 Participants n=4 Participants
Sex: Female, Male Male	134 Participants n=5 Participants	140 Participants n=7 Participants	152 Participants n=5 Participants	426 Participants n=4 Participants
Race/Ethnicity, Customized Asian	210 Participants n=5 Participants	216 Participants n=7 Participants	214 Participants n=5 Participants	640 Participants n=4 Participants

PRIMARY outcome

Timeframe: Baseline to Week 24 (prior to rescue)

Population: The full analysis set consisted of patients who were randomized, took at least 1 randomized study medication, and had both a baseline and at least 1 post-baseline efficacy assessment for the time point under consideration.

Outcome measures

Outcome measures
Measure	Saxagliptin + Metformin n=209 Participants Saxagliptin 5 mg + Metformin 500 mg	Saxagliptin + Placebo n=212 Participants Saxagliptin 5 mg + Placebo	Metformin + Placebo n=204 Participants Metformin 500 mg + Placebo
Change From Baseline in HbA1c From Baseline to Week 24 Provided That it is Prior to Rescue	-3.007 % HbA1c Standard Error 0.0706 • Interval -3.146 to -2.869	-2.123 % HbA1c Standard Error 0.0701 • Interval -2.26 to -1.985	-2.794 % HbA1c Standard Error 0.0715 • Interval -2.935 to -2.654

SECONDARY outcome

Timeframe: Week 24 (prior to rescue)

To evaluate the efficacy of the combination therapy (saxagliptin + metformin) when compared to placebo + metformin and placebo + saxagliptin with respect to the proportion of subjects achieving a therapeutic glycemic response defined as HbA1c \< 7.0% at the end of 24 weeks of double-blinded treatment.

Outcome measures

Outcome measures
Measure	Saxagliptin + Metformin n=209 Participants Saxagliptin 5 mg + Metformin 500 mg	Saxagliptin + Placebo n=212 Participants Saxagliptin 5 mg + Placebo	Metformin + Placebo n=204 Participants Metformin 500 mg + Placebo
Glycemic Response Defined as HbA1c < 7.0% at Week 24	81.8 Percentage of patients	44.3 Percentage of patients	71.1 Percentage of patients

SECONDARY outcome

Timeframe: Baseline to Week 24 prior to rescue

To evaluate the efficacy of the combination therapy (saxagliptin + metformin) when compared to placebo + metformin and placebo + saxagliptin with respect to reduction in fasting plasma glucose at the end of 24 weeks of double-blinded treatment.

Outcome measures

Outcome measures
Measure	Saxagliptin + Metformin n=210 Participants Saxagliptin 5 mg + Metformin 500 mg	Saxagliptin + Placebo n=213 Participants Saxagliptin 5 mg + Placebo	Metformin + Placebo n=207 Participants Metformin 500 mg + Placebo
Change From Baseline to Week 24 (Prior to Rescue) in Fasting Plasma Glucose	-3.25 mmol/L Standard Error 0.112	-1.86 mmol/L Standard Error 0.111	-2.94 mmol/L Standard Error 0.113

SECONDARY outcome

Timeframe: Baseline to Week 24 prior to rescue

Population: The full analysis set consisted of patients who were randomized, took at least 1 randomized study medication, had both a baseline and at least 1 post-baseline efficacy assessment for the time point under consideration, and participated in a meal tolerance test.

To evaluate the efficacy of the combination therapy (saxagliptin + metformin) when compared to placebo + metformin and placebo + saxagliptin with respect to change in 180-minute postprandial glucose response to a meal tolerance test at the end of 24 weeks of double-blinded treatment.

Outcome measures

Outcome measures
Measure	Saxagliptin + Metformin n=120 Participants Saxagliptin 5 mg + Metformin 500 mg	Saxagliptin + Placebo n=117 Participants Saxagliptin 5 mg + Placebo	Metformin + Placebo n=113 Participants Metformin 500 mg + Placebo
Change From Baseline to Week 24 (Prior to Rescue) in Area Under the Curve From 0-180 Minutes for Postprandial Glucose Response to a Meal Tolerance Test	-1027.8 mmol*min/L Standard Error 36.22	-611.9 mmol*min/L Standard Error 36.69	-858.5 mmol*min/L Standard Error 37.36

SECONDARY outcome

Timeframe: Week 24 (prior to rescue)

To evaluate the efficacy of the combination therapy (saxagliptin + metformin) when compared to placebo + metformin and placebo + saxagliptin with respect to the proportion of subjects achieving a therapeutic glycemic response defined as HbA1c ≤ 6.5% at the end of 24 weeks of double-blinded treatment.

Outcome measures

Outcome measures
Measure	Saxagliptin + Metformin n=209 Participants Saxagliptin 5 mg + Metformin 500 mg	Saxagliptin + Placebo n=212 Participants Saxagliptin 5 mg + Placebo	Metformin + Placebo n=204 Participants Metformin 500 mg + Placebo
Glycemic Response Defined as HbA1c ≤ 6.5% at Week 24	67.0 Percentage of patients	32.1 Percentage of patients	55.4 Percentage of patients

SECONDARY outcome

Timeframe: Baseline to Week 24 prior to rescue

To evaluate the efficacy of the combination therapy (saxagliptin + metformin) when compared to placebo + metformin and placebo + saxagliptin with respect to change in 120-minute postprandial glucose response to a meal tolerance test at the end of 24 weeks of double-blinded treatment.

Outcome measures

Outcome measures
Measure	Saxagliptin + Metformin n=122 Participants Saxagliptin 5 mg + Metformin 500 mg	Saxagliptin + Placebo n=121 Participants Saxagliptin 5 mg + Placebo	Metformin + Placebo n=116 Participants Metformin 500 mg + Placebo
Change From Baseline to Week 24 in 120-minute Postprandial Glucose Response to a Meal Tolerance Test	-7.09 mmol/L Standard Error 0.261	-4.12 mmol/L Standard Error 0.262	-5.95 mmol/L Standard Error 0.268

SECONDARY outcome

Timeframe: Baseline to Week 24

To evaluate the efficacy of the combination therapy (saxagliptin + metformin) when compared to placebo + metformin and placebo + saxagliptin with respect to the proportion of subjects requiring rescue for failing to achieve pre-specified glycemic targets or discontinuing for lack of efficacy within the 24 weeks of double-blinded treatment.

Outcome measures

Outcome measures
Measure	Saxagliptin + Metformin n=210 Participants Saxagliptin 5 mg + Metformin 500 mg	Saxagliptin + Placebo n=213 Participants Saxagliptin 5 mg + Placebo	Metformin + Placebo n=207 Participants Metformin 500 mg + Placebo
Patients Rescued for Failing to Achieve Pre-specified Glycemic Targets or Discontinuation for Lack of Efficacy During the 24-week Double-blind Treatment Phase	1.4 Percentage of patients	10.3 Percentage of patients	1.4 Percentage of patients

Adverse Events

METFORMIN + PLACEBO 5MG QD

Serious events: 11 serious events

Other events: 30 other events

Deaths: 0 deaths

SAXAGLIPTIN 5MG QD + METFORMIN

Serious events: 4 serious events

Other events: 37 other events

Deaths: 0 deaths

SAXAGLIPTIN 5MG QD + PLACEBO

Serious events: 12 serious events

Other events: 21 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	METFORMIN + PLACEBO 5MG QD n=210 participants at risk	SAXAGLIPTIN 5MG QD + METFORMIN n=215 participants at risk	SAXAGLIPTIN 5MG QD + PLACEBO n=214 participants at risk
Gastrointestinal disorders Diarrhoea	6.2% 13/210 • Number of events 19 Total number at risk is number of patients in safety analysis set (out of 640 randomized, 1 did not take study drug).	6.5% 14/215 • Number of events 17 Total number at risk is number of patients in safety analysis set (out of 640 randomized, 1 did not take study drug).	2.8% 6/214 • Number of events 6 Total number at risk is number of patients in safety analysis set (out of 640 randomized, 1 did not take study drug).
Infections and infestations Upper respiratory tract infection	6.7% 14/210 • Number of events 14 Total number at risk is number of patients in safety analysis set (out of 640 randomized, 1 did not take study drug).	7.0% 15/215 • Number of events 15 Total number at risk is number of patients in safety analysis set (out of 640 randomized, 1 did not take study drug).	4.7% 10/214 • Number of events 11 Total number at risk is number of patients in safety analysis set (out of 640 randomized, 1 did not take study drug).
Metabolism and nutrition disorders Hyperlipidaemia	3.3% 7/210 • Number of events 7 Total number at risk is number of patients in safety analysis set (out of 640 randomized, 1 did not take study drug).	5.1% 11/215 • Number of events 11 Total number at risk is number of patients in safety analysis set (out of 640 randomized, 1 did not take study drug).	2.8% 6/214 • Number of events 6 Total number at risk is number of patients in safety analysis set (out of 640 randomized, 1 did not take study drug).

Additional Information

Eva Johnsson, MD, PhD

AstraZeneca

Phone: 46 31 7762484

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	METFORMIN + PLACEBO 5MG QD n=210 participants at risk	SAXAGLIPTIN 5MG QD + METFORMIN n=215 participants at risk	SAXAGLIPTIN 5MG QD + PLACEBO n=214 participants at risk
Cardiac disorders Acute myocardial infarction	0.48% 1/210 • Number of events 1 Total number at risk is number of patients in safety analysis set (out of 640 randomized, 1 did not take study drug).	0.00% 0/215 Total number at risk is number of patients in safety analysis set (out of 640 randomized, 1 did not take study drug).	0.00% 0/214 Total number at risk is number of patients in safety analysis set (out of 640 randomized, 1 did not take study drug).
Eye disorders Cataract	0.00% 0/210 Total number at risk is number of patients in safety analysis set (out of 640 randomized, 1 did not take study drug).	0.00% 0/215 Total number at risk is number of patients in safety analysis set (out of 640 randomized, 1 did not take study drug).	0.47% 1/214 • Number of events 2 Total number at risk is number of patients in safety analysis set (out of 640 randomized, 1 did not take study drug).
Eye disorders Diabetic retinopathy	0.00% 0/210 Total number at risk is number of patients in safety analysis set (out of 640 randomized, 1 did not take study drug).	0.47% 1/215 • Number of events 1 Total number at risk is number of patients in safety analysis set (out of 640 randomized, 1 did not take study drug).	0.00% 0/214 Total number at risk is number of patients in safety analysis set (out of 640 randomized, 1 did not take study drug).
Gastrointestinal disorders Gastric ulcer	0.00% 0/210 Total number at risk is number of patients in safety analysis set (out of 640 randomized, 1 did not take study drug).	0.47% 1/215 • Number of events 1 Total number at risk is number of patients in safety analysis set (out of 640 randomized, 1 did not take study drug).	0.00% 0/214 Total number at risk is number of patients in safety analysis set (out of 640 randomized, 1 did not take study drug).
Gastrointestinal disorders Gastritis	0.48% 1/210 • Number of events 1 Total number at risk is number of patients in safety analysis set (out of 640 randomized, 1 did not take study drug).	0.00% 0/215 Total number at risk is number of patients in safety analysis set (out of 640 randomized, 1 did not take study drug).	0.00% 0/214 Total number at risk is number of patients in safety analysis set (out of 640 randomized, 1 did not take study drug).
Gastrointestinal disorders Large intestine polyp	0.48% 1/210 • Number of events 1 Total number at risk is number of patients in safety analysis set (out of 640 randomized, 1 did not take study drug).	0.00% 0/215 Total number at risk is number of patients in safety analysis set (out of 640 randomized, 1 did not take study drug).	0.00% 0/214 Total number at risk is number of patients in safety analysis set (out of 640 randomized, 1 did not take study drug).
Gastrointestinal disorders Pancreatic mass	0.48% 1/210 • Number of events 1 Total number at risk is number of patients in safety analysis set (out of 640 randomized, 1 did not take study drug).	0.00% 0/215 Total number at risk is number of patients in safety analysis set (out of 640 randomized, 1 did not take study drug).	0.00% 0/214 Total number at risk is number of patients in safety analysis set (out of 640 randomized, 1 did not take study drug).
Hepatobiliary disorders Bile duct obstruction	0.48% 1/210 • Number of events 1 Total number at risk is number of patients in safety analysis set (out of 640 randomized, 1 did not take study drug).	0.00% 0/215 Total number at risk is number of patients in safety analysis set (out of 640 randomized, 1 did not take study drug).	0.00% 0/214 Total number at risk is number of patients in safety analysis set (out of 640 randomized, 1 did not take study drug).
Hepatobiliary disorders Cholecystitis	0.48% 1/210 • Number of events 1 Total number at risk is number of patients in safety analysis set (out of 640 randomized, 1 did not take study drug).	0.00% 0/215 Total number at risk is number of patients in safety analysis set (out of 640 randomized, 1 did not take study drug).	0.00% 0/214 Total number at risk is number of patients in safety analysis set (out of 640 randomized, 1 did not take study drug).
Hepatobiliary disorders Cholecystitis acute	0.00% 0/210 Total number at risk is number of patients in safety analysis set (out of 640 randomized, 1 did not take study drug).	0.47% 1/215 • Number of events 1 Total number at risk is number of patients in safety analysis set (out of 640 randomized, 1 did not take study drug).	0.00% 0/214 Total number at risk is number of patients in safety analysis set (out of 640 randomized, 1 did not take study drug).
Hepatobiliary disorders Cholelithiasis	0.48% 1/210 • Number of events 1 Total number at risk is number of patients in safety analysis set (out of 640 randomized, 1 did not take study drug).	0.00% 0/215 Total number at risk is number of patients in safety analysis set (out of 640 randomized, 1 did not take study drug).	0.00% 0/214 Total number at risk is number of patients in safety analysis set (out of 640 randomized, 1 did not take study drug).
Hepatobiliary disorders Hepatitis alcoholic	0.00% 0/210 Total number at risk is number of patients in safety analysis set (out of 640 randomized, 1 did not take study drug).	0.00% 0/215 Total number at risk is number of patients in safety analysis set (out of 640 randomized, 1 did not take study drug).	0.47% 1/214 • Number of events 1 Total number at risk is number of patients in safety analysis set (out of 640 randomized, 1 did not take study drug).
Infections and infestations Chronic hepatitis B	0.00% 0/210 Total number at risk is number of patients in safety analysis set (out of 640 randomized, 1 did not take study drug).	0.00% 0/215 Total number at risk is number of patients in safety analysis set (out of 640 randomized, 1 did not take study drug).	0.47% 1/214 • Number of events 1 Total number at risk is number of patients in safety analysis set (out of 640 randomized, 1 did not take study drug).
Infections and infestations Localised infection	0.48% 1/210 • Number of events 1 Total number at risk is number of patients in safety analysis set (out of 640 randomized, 1 did not take study drug).	0.00% 0/215 Total number at risk is number of patients in safety analysis set (out of 640 randomized, 1 did not take study drug).	0.00% 0/214 Total number at risk is number of patients in safety analysis set (out of 640 randomized, 1 did not take study drug).
Infections and infestations Tuberculosis	0.00% 0/210 Total number at risk is number of patients in safety analysis set (out of 640 randomized, 1 did not take study drug).	0.00% 0/215 Total number at risk is number of patients in safety analysis set (out of 640 randomized, 1 did not take study drug).	0.47% 1/214 • Number of events 1 Total number at risk is number of patients in safety analysis set (out of 640 randomized, 1 did not take study drug).
Injury, poisoning and procedural complications Humerus fracture	0.00% 0/210 Total number at risk is number of patients in safety analysis set (out of 640 randomized, 1 did not take study drug).	0.00% 0/215 Total number at risk is number of patients in safety analysis set (out of 640 randomized, 1 did not take study drug).	0.47% 1/214 • Number of events 1 Total number at risk is number of patients in safety analysis set (out of 640 randomized, 1 did not take study drug).
Injury, poisoning and procedural complications Injury	0.00% 0/210 Total number at risk is number of patients in safety analysis set (out of 640 randomized, 1 did not take study drug).	0.00% 0/215 Total number at risk is number of patients in safety analysis set (out of 640 randomized, 1 did not take study drug).	0.47% 1/214 • Number of events 1 Total number at risk is number of patients in safety analysis set (out of 640 randomized, 1 did not take study drug).
Musculoskeletal and connective tissue disorders Musculoskeletal pain	0.00% 0/210 Total number at risk is number of patients in safety analysis set (out of 640 randomized, 1 did not take study drug).	0.47% 1/215 • Number of events 1 Total number at risk is number of patients in safety analysis set (out of 640 randomized, 1 did not take study drug).	0.00% 0/214 Total number at risk is number of patients in safety analysis set (out of 640 randomized, 1 did not take study drug).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Adrenal adenoma	0.00% 0/210 Total number at risk is number of patients in safety analysis set (out of 640 randomized, 1 did not take study drug).	0.00% 0/215 Total number at risk is number of patients in safety analysis set (out of 640 randomized, 1 did not take study drug).	0.47% 1/214 • Number of events 1 Total number at risk is number of patients in safety analysis set (out of 640 randomized, 1 did not take study drug).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Adrenal neoplasm	0.00% 0/210 Total number at risk is number of patients in safety analysis set (out of 640 randomized, 1 did not take study drug).	0.00% 0/215 Total number at risk is number of patients in safety analysis set (out of 640 randomized, 1 did not take study drug).	0.47% 1/214 • Number of events 1 Total number at risk is number of patients in safety analysis set (out of 640 randomized, 1 did not take study drug).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Plasma cell myeloma	0.48% 1/210 • Number of events 1 Total number at risk is number of patients in safety analysis set (out of 640 randomized, 1 did not take study drug).	0.00% 0/215 Total number at risk is number of patients in safety analysis set (out of 640 randomized, 1 did not take study drug).	0.00% 0/214 Total number at risk is number of patients in safety analysis set (out of 640 randomized, 1 did not take study drug).
Nervous system disorders Cerebral infarction	0.48% 1/210 • Number of events 1 Total number at risk is number of patients in safety analysis set (out of 640 randomized, 1 did not take study drug).	0.00% 0/215 Total number at risk is number of patients in safety analysis set (out of 640 randomized, 1 did not take study drug).	0.47% 1/214 • Number of events 1 Total number at risk is number of patients in safety analysis set (out of 640 randomized, 1 did not take study drug).
Nervous system disorders Diabetic neuropathy	0.48% 1/210 • Number of events 1 Total number at risk is number of patients in safety analysis set (out of 640 randomized, 1 did not take study drug).	0.00% 0/215 Total number at risk is number of patients in safety analysis set (out of 640 randomized, 1 did not take study drug).	0.00% 0/214 Total number at risk is number of patients in safety analysis set (out of 640 randomized, 1 did not take study drug).
Renal and urinary disorders Diabetic nephropathy	0.00% 0/210 Total number at risk is number of patients in safety analysis set (out of 640 randomized, 1 did not take study drug).	0.00% 0/215 Total number at risk is number of patients in safety analysis set (out of 640 randomized, 1 did not take study drug).	0.47% 1/214 • Number of events 1 Total number at risk is number of patients in safety analysis set (out of 640 randomized, 1 did not take study drug).
Renal and urinary disorders Glomerulonephritis chronic	0.48% 1/210 • Number of events 1 Total number at risk is number of patients in safety analysis set (out of 640 randomized, 1 did not take study drug).	0.00% 0/215 Total number at risk is number of patients in safety analysis set (out of 640 randomized, 1 did not take study drug).	0.00% 0/214 Total number at risk is number of patients in safety analysis set (out of 640 randomized, 1 did not take study drug).
Renal and urinary disorders Ureterolithiasis	0.00% 0/210 Total number at risk is number of patients in safety analysis set (out of 640 randomized, 1 did not take study drug).	0.00% 0/215 Total number at risk is number of patients in safety analysis set (out of 640 randomized, 1 did not take study drug).	0.47% 1/214 • Number of events 1 Total number at risk is number of patients in safety analysis set (out of 640 randomized, 1 did not take study drug).
Respiratory, thoracic and mediastinal disorders Pulmonary mass	0.00% 0/210 Total number at risk is number of patients in safety analysis set (out of 640 randomized, 1 did not take study drug).	0.00% 0/215 Total number at risk is number of patients in safety analysis set (out of 640 randomized, 1 did not take study drug).	0.47% 1/214 • Number of events 1 Total number at risk is number of patients in safety analysis set (out of 640 randomized, 1 did not take study drug).
Vascular disorders Hypertension	0.48% 1/210 • Number of events 1 Total number at risk is number of patients in safety analysis set (out of 640 randomized, 1 did not take study drug).	0.00% 0/215 Total number at risk is number of patients in safety analysis set (out of 640 randomized, 1 did not take study drug).	0.47% 1/214 • Number of events 1 Total number at risk is number of patients in safety analysis set (out of 640 randomized, 1 did not take study drug).
Vascular disorders Phlebitis	0.00% 0/210 Total number at risk is number of patients in safety analysis set (out of 640 randomized, 1 did not take study drug).	0.00% 0/215 Total number at risk is number of patients in safety analysis set (out of 640 randomized, 1 did not take study drug).	0.47% 1/214 • Number of events 1 Total number at risk is number of patients in safety analysis set (out of 640 randomized, 1 did not take study drug).