Trial Outcomes & Findings for Evaluate the Efficacy and Safety of Saxagliptin Added to Insulin Monotherapy or to Insulin Combined With Metformin in Chinese Subjects With Type 2 Diabetes Who Have Inadequate Glycaemic Control (NCT NCT02104804)

NCT ID: NCT02104804

Last Updated: 2017-10-02

Results Overview

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

953 participants

Primary outcome timeframe

Baseline to 24 weeks

Results posted on

2017-10-02

Participant Flow

This study was performed at 22 sites in the People's Republic of China (PRC).The first patient was enrolled on 07 May 2014 and the last patient completed the study on 26 February 2016. The study was divided into a single-blind placebo lead-in period of 8 weeks, a treatment period of 24 weeks and a follow-up phase of 4 weeks.

953 patients were enrolled, of which 641 patients took at least 1 dose of study drug and entered the lead-in period. A total of 312 patients did not enter the lead-in period (289 did not fulfill eligibility criteria, 21 due to subject decision, 1 each for severe non-compliance to protocol and other reasons) and 466 patients were randomized.

Participant milestones

Participant milestones
Measure	Saxagliptin Plus Insulin Saxagliptin 5 mg plus insulin	Vs. Placebo Plus Insulin Patients receiving placebo 5 mg plus insulin
Overall Study STARTED	234	232
Overall Study COMPLETED	218	213
Overall Study NOT COMPLETED	16	19

Reasons for withdrawal

Reasons for withdrawal
Measure	Saxagliptin Plus Insulin Saxagliptin 5 mg plus insulin	Vs. Placebo Plus Insulin Patients receiving placebo 5 mg plus insulin
Overall Study Did not take study medication	0	1
Overall Study Study specific discontinuation criteria	6	1
Overall Study Other listed	2	1
Overall Study Protocol Violation	0	1
Overall Study Adverse Event	4	3
Overall Study Withdrawal by Subject	4	12

Baseline Characteristics

Evaluate the Efficacy and Safety of Saxagliptin Added to Insulin Monotherapy or to Insulin Combined With Metformin in Chinese Subjects With Type 2 Diabetes Who Have Inadequate Glycaemic Control

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Saxagliptin Plus Insulin n=232 Participants Saxagliptin 5 mg plus insulin	Vs. Placebo Plus Insulin n=230 Participants Patients receiving placebo 5 mg plus insulin	Total n=462 Participants Total of all reporting groups
Age, Continuous	59.3 Years STANDARD_DEVIATION 7.93 • n=5 Participants	58.9 Years STANDARD_DEVIATION 8.17 • n=7 Participants	59.1 Years STANDARD_DEVIATION 8.05 • n=5 Participants
Sex: Female, Male Female	123 Participants n=5 Participants	130 Participants n=7 Participants	253 Participants n=5 Participants
Sex: Female, Male Male	109 Participants n=5 Participants	100 Participants n=7 Participants	209 Participants n=5 Participants
Baseline HbA1C	8.52 % STANDARD_DEVIATION 0.69 • n=5 Participants	8.53 % STANDARD_DEVIATION 0.70 • n=7 Participants	8.53 % STANDARD_DEVIATION 0.69 • n=5 Participants
Duration of diabetes	13.4 Years STANDARD_DEVIATION 7.28 • n=5 Participants	13.3 Years STANDARD_DEVIATION 6.35 • n=7 Participants	13.4 Years STANDARD_DEVIATION 6.83 • n=5 Participants
Fasting Plasma Glucose (FPG)	167.94 mg/dL STANDARD_DEVIATION 31.39 • n=5 Participants	167.34 mg/dL STANDARD_DEVIATION 32.86 • n=7 Participants	167.64 mg/dL STANDARD_DEVIATION 32.10 • n=5 Participants
0-180 min Post Prandial Glucose AUC	45457.6 mg*min/dL STANDARD_DEVIATION 8433.08 • n=5 Participants	43851.4 mg*min/dL STANDARD_DEVIATION 9051.26 • n=7 Participants	44661.5 mg*min/dL STANDARD_DEVIATION 8772.22 • n=5 Participants
120-min Post Prandial Glucose	278.0 mg/dL STANDARD_DEVIATION 58.00 • n=5 Participants	270.0 mg/dL STANDARD_DEVIATION 63.30 • n=7 Participants	274.0 mg/dL STANDARD_DEVIATION 60.76 • n=5 Participants
Fasting Glucagon	40.007 pg/dL STANDARD_DEVIATION 23.68 • n=5 Participants	40.231 pg/dL STANDARD_DEVIATION 21.06 • n=7 Participants	40.119 pg/dL STANDARD_DEVIATION 22.39 • n=5 Participants
Fasting C-peptide	1.029 ng/dL STANDARD_DEVIATION 0.52 • n=5 Participants	1.012 ng/dL STANDARD_DEVIATION 0.58 • n=7 Participants	1.020 ng/dL STANDARD_DEVIATION 0.55 • n=5 Participants
Metformin use at enrolment Yes	155 Participants n=5 Participants	154 Participants n=7 Participants	309 Participants n=5 Participants
Metformin use at enrolment No	77 Participants n=5 Participants	76 Participants n=7 Participants	153 Participants n=5 Participants
Mean Tolerated Daily Dose of Insulin	38.6 Insulin Dose Units STANDARD_DEVIATION 16.49 • n=5 Participants	38.9 Insulin Dose Units STANDARD_DEVIATION 14.68 • n=7 Participants	38.7 Insulin Dose Units STANDARD_DEVIATION 15.60 • n=5 Participants

PRIMARY outcome

Timeframe: Baseline to 24 weeks

Population: 229 and 227 indicate the number of participants with non-missing baseline and Week 24 values in the Full Analysis Set of 232 and 230 respectively.

Outcome measures

Outcome measures
Measure	Saxagliptin Plus Insulin n=229 Participants Saxagliptin 5 mg plus insulin	Vs. Placebo Plus Insulin n=227 Participants Patients receiving placebo 5 mg plus insulin
Change in HbA1c From Baseline to Week 24	-0.64 Percentage change Interval -0.74 to -0.55	-0.06 Percentage change Interval -0.16 to 0.04

SECONDARY outcome

Timeframe: Baseline to 24 weeks

Population: 213 and 206 indicate the number of participants with non-missing baseline and Week 24 values in the Full Analysis Set of 232 and 230 respectively.

Outcome measures

Outcome measures
Measure	Saxagliptin Plus Insulin n=213 Participants Saxagliptin 5 mg plus insulin	Vs. Placebo Plus Insulin n=206 Participants Patients receiving placebo 5 mg plus insulin
Change in Postprandial Glucose AUC From Baseline to Week 24 During a Meal Tolerance Test	-4702.2 mg*min/dL Interval -5813.3 to -3591.0	1431.0 mg*min/dL Interval 294.4 to 2567.7

SECONDARY outcome

Timeframe: Baseline to 24 weeks

Population: 215 and 211 indicate the number of participants with non-missing baseline and Week 24 values in the Full Analysis Set of 232 and 230 respectively.

Outcome measures

Outcome measures
Measure	Saxagliptin Plus Insulin n=215 Participants Saxagliptin 5 mg plus insulin	Vs. Placebo Plus Insulin n=211 Participants Patients receiving placebo 5 mg plus insulin
Analysis of Change in 120-minute PPG From Baseline to Week 24 During a Meal Tolerance Test	-30.28 mg/dL Interval -37.76 to -22.8	8.84 mg/dL Interval 1.25 to 16.42

SECONDARY outcome

Timeframe: At Week 24

Population: 229 and 227 indicate the number of participants with non-missing baseline and Week 24 values in the Full Analysis Set of 232 and 230 respectively.

Outcome measures

Outcome measures
Measure	Saxagliptin Plus Insulin n=229 Participants Saxagliptin 5 mg plus insulin	Vs. Placebo Plus Insulin n=227 Participants Patients receiving placebo 5 mg plus insulin
Percentage of Patients Achieving a Therapeutic Glycaemic Response of HbA1c <7%	11.4 % of participants	3.5 % of participants

SECONDARY outcome

Timeframe: Baseline to Average of Weeks 20 and 24

Population: 232 and 229 indicate the number of participants with non-missing baseline and Week 24 values in the Full Analysis Set of 232 and 229 for this outcome measure respectively.

Outcome measures

Outcome measures
Measure	Saxagliptin Plus Insulin n=232 Participants Saxagliptin 5 mg plus insulin	Vs. Placebo Plus Insulin n=229 Participants Patients receiving placebo 5 mg plus insulin
The Analysis of Change in Fasting Plasma Glucose From Baseline to Week 24 (This Was the Average of Weeks 20 and 24)	-11.23 mg/dL Interval -15.34 to -7.11	4.65 mg/dL Interval 0.5 to 8.8

SECONDARY outcome

Timeframe: Baseline to 24 weeks

Population: 232 and 230 indicate the number of participants with non-missing baseline and Week 24 values in the Full Analysis Set of 232 and 230 respectively.

Outcome measures

Outcome measures
Measure	Saxagliptin Plus Insulin n=232 Participants Saxagliptin 5 mg plus insulin	Vs. Placebo Plus Insulin n=230 Participants Patients receiving placebo 5 mg plus insulin
Analysis of Change in Mean Total Daily Dose of Insulin From Baseline to Week 24	-0.09 IU Interval -0.32 to 0.14	0.04 IU Interval -0.19 to 0.27

Adverse Events

PLACEBO QD + INSULIN WITH OR WITHOUT METFORMIN

Serious events: 14 serious events

Other events: 96 other events

Deaths: 0 deaths

SAXAGLIPTIN 5 MG QD + INSULIN WITH OR WITHOUT METFORMIN

Serious events: 12 serious events

Other events: 89 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Eva Johnsson, MD, PhD, Global Clinical Lead

AstraZeneca

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Without limitation to any other right of AstraZeneca hereunder, Institution and Principal Investigator acknowledge and agree that only AZ as Sponsor will register the Study and post the Study results in accordance with AZ internal policy on one or more publicly-accessible trial registries and websites (including the publicly-funded website http://www.clinicaltrials.gov/ and on its own website http://www.astrazenecaclinicaltrials.com) to avoid duplication.
Publication restrictions are in place

Restriction type: OTHER

Measure	PLACEBO QD + INSULIN WITH OR WITHOUT METFORMIN n=231 participants at risk	SAXAGLIPTIN 5 MG QD + INSULIN WITH OR WITHOUT METFORMIN n=234 participants at risk
Musculoskeletal and connective tissue disorders Ankylosing spondylitis	0.43% 1/231 • Number of events 1 Total numbers at risk indicate the number of participants in the Safety Analysis set. Out of 466 randomized, 1 did not take study drug.	0.00% 0/234 Total numbers at risk indicate the number of participants in the Safety Analysis set. Out of 466 randomized, 1 did not take study drug.
Musculoskeletal and connective tissue disorders Intervertebral disc protrusion	0.00% 0/231 Total numbers at risk indicate the number of participants in the Safety Analysis set. Out of 466 randomized, 1 did not take study drug.	0.43% 1/234 • Number of events 1 Total numbers at risk indicate the number of participants in the Safety Analysis set. Out of 466 randomized, 1 did not take study drug.
Cardiac disorders Acute myocardial infarction	0.00% 0/231 Total numbers at risk indicate the number of participants in the Safety Analysis set. Out of 466 randomized, 1 did not take study drug.	0.43% 1/234 • Number of events 1 Total numbers at risk indicate the number of participants in the Safety Analysis set. Out of 466 randomized, 1 did not take study drug.
Cardiac disorders Cardiac failure	0.00% 0/231 Total numbers at risk indicate the number of participants in the Safety Analysis set. Out of 466 randomized, 1 did not take study drug.	0.43% 1/234 • Number of events 1 Total numbers at risk indicate the number of participants in the Safety Analysis set. Out of 466 randomized, 1 did not take study drug.
Ear and labyrinth disorders Deafness neurosensory	0.43% 1/231 • Number of events 1 Total numbers at risk indicate the number of participants in the Safety Analysis set. Out of 466 randomized, 1 did not take study drug.	0.00% 0/234 Total numbers at risk indicate the number of participants in the Safety Analysis set. Out of 466 randomized, 1 did not take study drug.
Eye disorders Vitreous haemorrhage	0.43% 1/231 • Number of events 1 Total numbers at risk indicate the number of participants in the Safety Analysis set. Out of 466 randomized, 1 did not take study drug.	0.00% 0/234 Total numbers at risk indicate the number of participants in the Safety Analysis set. Out of 466 randomized, 1 did not take study drug.
Gastrointestinal disorders Intestinal obstruction	0.43% 1/231 • Number of events 1 Total numbers at risk indicate the number of participants in the Safety Analysis set. Out of 466 randomized, 1 did not take study drug.	0.00% 0/234 Total numbers at risk indicate the number of participants in the Safety Analysis set. Out of 466 randomized, 1 did not take study drug.
Gastrointestinal disorders Pancreatitis acute	0.43% 1/231 • Number of events 1 Total numbers at risk indicate the number of participants in the Safety Analysis set. Out of 466 randomized, 1 did not take study drug.	0.00% 0/234 Total numbers at risk indicate the number of participants in the Safety Analysis set. Out of 466 randomized, 1 did not take study drug.
Infections and infestations Hepatitis E	0.43% 1/231 • Number of events 1 Total numbers at risk indicate the number of participants in the Safety Analysis set. Out of 466 randomized, 1 did not take study drug.	0.00% 0/234 Total numbers at risk indicate the number of participants in the Safety Analysis set. Out of 466 randomized, 1 did not take study drug.
Infections and infestations Urethritis	0.00% 0/231 Total numbers at risk indicate the number of participants in the Safety Analysis set. Out of 466 randomized, 1 did not take study drug.	0.43% 1/234 • Number of events 1 Total numbers at risk indicate the number of participants in the Safety Analysis set. Out of 466 randomized, 1 did not take study drug.
Injury, poisoning and procedural complications Ankle fracture	0.00% 0/231 Total numbers at risk indicate the number of participants in the Safety Analysis set. Out of 466 randomized, 1 did not take study drug.	0.43% 1/234 • Number of events 1 Total numbers at risk indicate the number of participants in the Safety Analysis set. Out of 466 randomized, 1 did not take study drug.
Injury, poisoning and procedural complications Fracture	0.43% 1/231 • Number of events 1 Total numbers at risk indicate the number of participants in the Safety Analysis set. Out of 466 randomized, 1 did not take study drug.	0.00% 0/234 Total numbers at risk indicate the number of participants in the Safety Analysis set. Out of 466 randomized, 1 did not take study drug.
Injury, poisoning and procedural complications Lumbar vertebral fracture	0.43% 1/231 • Number of events 1 Total numbers at risk indicate the number of participants in the Safety Analysis set. Out of 466 randomized, 1 did not take study drug.	0.00% 0/234 Total numbers at risk indicate the number of participants in the Safety Analysis set. Out of 466 randomized, 1 did not take study drug.
Injury, poisoning and procedural complications Road traffic accident	0.00% 0/231 Total numbers at risk indicate the number of participants in the Safety Analysis set. Out of 466 randomized, 1 did not take study drug.	0.43% 1/234 • Number of events 1 Total numbers at risk indicate the number of participants in the Safety Analysis set. Out of 466 randomized, 1 did not take study drug.
Metabolism and nutrition disorders Diabetes mellitus	0.43% 1/231 • Number of events 1 Total numbers at risk indicate the number of participants in the Safety Analysis set. Out of 466 randomized, 1 did not take study drug.	0.00% 0/234 Total numbers at risk indicate the number of participants in the Safety Analysis set. Out of 466 randomized, 1 did not take study drug.
Metabolism and nutrition disorders Diabetes mellitus inadequate control	0.87% 2/231 • Number of events 2 Total numbers at risk indicate the number of participants in the Safety Analysis set. Out of 466 randomized, 1 did not take study drug.	0.43% 1/234 • Number of events 1 Total numbers at risk indicate the number of participants in the Safety Analysis set. Out of 466 randomized, 1 did not take study drug.
Metabolism and nutrition disorders Hyperglycaemia	0.00% 0/231 Total numbers at risk indicate the number of participants in the Safety Analysis set. Out of 466 randomized, 1 did not take study drug.	0.43% 1/234 • Number of events 1 Total numbers at risk indicate the number of participants in the Safety Analysis set. Out of 466 randomized, 1 did not take study drug.
Metabolism and nutrition disorders Hypoglycaemia	0.43% 1/231 • Number of events 1 Total numbers at risk indicate the number of participants in the Safety Analysis set. Out of 466 randomized, 1 did not take study drug.	0.00% 0/234 Total numbers at risk indicate the number of participants in the Safety Analysis set. Out of 466 randomized, 1 did not take study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Gastric cancer	0.43% 1/231 • Number of events 1 Total numbers at risk indicate the number of participants in the Safety Analysis set. Out of 466 randomized, 1 did not take study drug.	0.00% 0/234 Total numbers at risk indicate the number of participants in the Safety Analysis set. Out of 466 randomized, 1 did not take study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Gastrointestinal carcinoma	0.00% 0/231 Total numbers at risk indicate the number of participants in the Safety Analysis set. Out of 466 randomized, 1 did not take study drug.	0.43% 1/234 • Number of events 1 Total numbers at risk indicate the number of participants in the Safety Analysis set. Out of 466 randomized, 1 did not take study drug.
Nervous system disorders Basal ganglia haemorrhage	0.00% 0/231 Total numbers at risk indicate the number of participants in the Safety Analysis set. Out of 466 randomized, 1 did not take study drug.	0.43% 1/234 • Number of events 1 Total numbers at risk indicate the number of participants in the Safety Analysis set. Out of 466 randomized, 1 did not take study drug.
Nervous system disorders Cerebral infarction	0.00% 0/231 Total numbers at risk indicate the number of participants in the Safety Analysis set. Out of 466 randomized, 1 did not take study drug.	0.85% 2/234 • Number of events 2 Total numbers at risk indicate the number of participants in the Safety Analysis set. Out of 466 randomized, 1 did not take study drug.
Nervous system disorders Cerebral ischaemia	0.43% 1/231 • Number of events 1 Total numbers at risk indicate the number of participants in the Safety Analysis set. Out of 466 randomized, 1 did not take study drug.	0.00% 0/234 Total numbers at risk indicate the number of participants in the Safety Analysis set. Out of 466 randomized, 1 did not take study drug.
Nervous system disorders Lacunar infarction	0.00% 0/231 Total numbers at risk indicate the number of participants in the Safety Analysis set. Out of 466 randomized, 1 did not take study drug.	0.43% 1/234 • Number of events 1 Total numbers at risk indicate the number of participants in the Safety Analysis set. Out of 466 randomized, 1 did not take study drug.
Nervous system disorders Subarachnoid haemorrhage	0.43% 1/231 • Number of events 1 Total numbers at risk indicate the number of participants in the Safety Analysis set. Out of 466 randomized, 1 did not take study drug.	0.00% 0/234 Total numbers at risk indicate the number of participants in the Safety Analysis set. Out of 466 randomized, 1 did not take study drug.
Renal and urinary disorders Calculus ureteric	0.00% 0/231 Total numbers at risk indicate the number of participants in the Safety Analysis set. Out of 466 randomized, 1 did not take study drug.	0.43% 1/234 • Number of events 1 Total numbers at risk indicate the number of participants in the Safety Analysis set. Out of 466 randomized, 1 did not take study drug.
Vascular disorders Hypertension	0.43% 1/231 • Number of events 1 Total numbers at risk indicate the number of participants in the Safety Analysis set. Out of 466 randomized, 1 did not take study drug.	0.00% 0/234 Total numbers at risk indicate the number of participants in the Safety Analysis set. Out of 466 randomized, 1 did not take study drug.