Saxagliptin compared to glimepiride in elderly type 2 diabetes patients, with inadequate glycemic control on metformin - GENERATION

Study identifier:D1680L00002

ClinicalTrials.gov identifier:N/A

EudraCT identifier:N/A

CTIS identifier:N/A

Study Complete

Official Title

A 52-Week, Randomised, Double Blind, Active-Controlled, Multi-Centre Phase IIIb/IV Study to Evaluate the Efficacy and Tolerability of Saxagliptin Compared to Glimepiride in Elderly Patients with Type 2 Diabetes Mellitus Who Have Inadequate Glycaemic Control on Metformin Monotherapy

Medical condition

Type 2 Diabetes Mellitus

Phase

Phase 4

Healthy volunteers

Study drug

Saxagliptin, Glimepiride

Sex

All

Actual Enrollment

957

Study type

Interventional

Age

65 Years +

Date

Study Start Date: 01 Oct 2009

Primary Completion Date: 01 Jun 2012

Study Completion Date: 01 Jun 2012

Study design

Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind
Primary Purpose: Treatment

Verification:

Verified 01 Apr 2015 by AstraZeneca

Collaborators

Bristol-Myers Squibb

Inclusion and exclusion criteria

Location

Research Site

FELDBACH, Austria

Location

Research Site

GRAZ, Austria

Location

Research Site

SALZBURG, Austria

Location

Research Site

VIENNA, Austria

Location

Research Site

WIEN, Austria

Location

Research Site

AALBORG, Denmark

Location

Research Site

ANS BY, Denmark

Location

Research Site

KJELLERUP, Denmark

Arms	Assigned Interventions
Experimental: 1 Saxagliptin 5 mg	Drug: Saxagliptin 5 mg, oral tablet, once daily Other Name: Onglyza
Active Comparator: 2 Glimepiride 1 - 6 mg	Drug: Glimepiride 1, 2, 3, 4 or 6 mg, oral encapsulated tablet, once daily Other Name: Amaryl

Participant Flow

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
In total, 152 study centres in 13 countries recruited patients in this study. The first patient was enrolled in the study on 20 October 2009, and the last patient completed the study on 14 June 2012. 957 subjects were enrolled. 753 were deemed eligible for lead-in and 720 were randomized.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
A 2-week single-blind (to patient only) placebo lead-in period occurred from Week -2 to Week 0. Patients were from this period on,counselled on dietary and lifestyle modifications according to usual clinical routine. They were given a glucometer to check their plasma glucose at home at least every second day.

Reporting Groups

	Description
Saxagliptin 5 mg	Saxagliptin 5 mg, oral tablet, once daily
Glimepiride 1 - 6 mg	Glimepiride : 1, 2, 3, 4 or 6 mg, oral encapsulated tablet, once daily

Participant Flow: Overall Study

	Saxagliptin 5 mg	Glimepiride 1 - 6 mg
STARTED	360^[1]	360^[2]
COMPLETED	289	285
NOT COMPLETED	71	75
Withdrawal by Subject	17	19
Lost to Follow-up	0	1
Safety reason	1	1
Protocol Violation	1	3
Incorrect enrolment	0	2
Adverse Event	15	7
Death	1	1
Study specific discontinuation criteria	33	34
Other	3	7

[1]	Completed lead-in period and were randomised
[2]	Completed lead-in period and were randomised

Baseline Characteristics

Analysis Population Description -- Explanation of how the number of participants for analysis was determined.

Reporting Groups

	Description
Saxagliptin 5 mg	Saxagliptin 5 mg, oral tablet, once daily
Glimepiride 1 - 6 mg	Glimepiride 1, 2, 3, 4 or 6 mg, oral encapsulated tablet, once daily

Baseline Measures

	Saxagliptin 5 mg	Glimepiride 1 - 6 mg	Total
Number of Participants [units: Participants]	360	360	720
Age Categorical [units: participants]
<=18 years	0	0	0
Between 18 and 65 years	0	0	0
>=65 years	360	360	720
Age Continuous [units: years] Mean ± Standard Deviation	72.5 ± 5.72	72.7 ± 5.44	72.6 ± 5.58
Gender, Male/Female [units: participants]
Female	143	132	275
Male	217	228	445
Region of Enrollment [units: participants]
Greece	21	18	39
Finland	24	19	43
Spain	31	25	56
Austria	30	15	45
United Kingdom	39	49	88
Italy	12	12	24
France	11	13	24
Hungary	9	9	18
Mexico	10	7	17
Denmark	16	17	33
Germany	44	55	99
Norway	47	59	106
Sweden	66	62	128

Outcome Measures

1. Primary Outcome Measure: Proportion of patients reaching HbA1c <7% after 52 weeks of treatment without confirmed or severe hypoglycaemia. [ Time Frame: From week 0 to week 52. ]

Measure Type	Primary
Measure Name	Proportion of patients reaching HbA1c <7% after 52 weeks of treatment without confirmed or severe hypoglycaemia.
Measure Description	Defined as obtained on or before the 8th day after the last dosing day, as determined by central laboratory. Safety analysis set. Confirmed hypoglycaemia defined as: any event defined as either a symptomatic event with blood glucose level <3 mmol/L (<54 mg/dL) and no need for external assistance, or an asymptomatic blood glucose measurement <3 mmol/L (<54 mg/dL). Major (or severe) hypoglycaemia defined as: symptomatic events requiring external assistance due to severe impairment in consciousness or behaviour, with or without blood glucose level <3 mmol/L (<54 mg/dL), but with prompt recovery after glucose or glucagon administration. These events may be associated with sufficient neuroglycopenia to induce seizure or coma. Plasma glucose measurements may not be available during such an event, but neurological recovery, attributable to the restoration of plasma glucose to normal, was considered sufficient evidence that the event was induced by a low plasma glucose concentration.
Time Frame	From week 0 to week 52.
Safety Issue?	Yes

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Safety analysis set (a subset of the randomised analysis set including patients who took at least one investigational product dose).

Reporting Groups

	Description
Saxagliptin 5 mg	Saxagliptin 5 mg, oral tablet, once daily
Glimepiride 1 - 6 mg	Glimepiride 1, 2, 3, 4 or 6 mg, oral encapsulated tablet, once daily

Measured Values

	Saxagliptin 5 mg	Glimepiride 1 - 6 mg
Number of Participants Analyzed [units:participants]	359	359
Proportion of patients reaching HbA1c <7% after 52 weeks of treatment without confirmed or severe hypoglycaemia. [units: percentage of participants]
All patients	37.9	38.2
patients aged <75 years (n=217, n=216)	39.2	33.3
patients aged ≥75 years (n=142, n=143)	35.9	45.5

No statistical analysis provided for Proportion of patients reaching HbA1c <7% after 52 weeks of treatment without confirmed or severe hypoglycaemia.

2. Secondary Outcome Measure: Proportion of Patients Having Experienced at Least One Hypoglycaemic Event (Confirmed or Severe) over the 52-week Double-blind Treatment Period. [ Time Frame: From week 0 to week 52. ]

Measure Type	Secondary
Measure Name	Proportion of Patients Having Experienced at Least One Hypoglycaemic Event (Confirmed or Severe) over the 52-week Double-blind Treatment Period.
Measure Description	Hypoglyceamic event defined as, Confirmed hypoglycaemia: any event defined as either a symptomatic event with blood glucose level <3 mmol/L (<54 mg/dL) and no need for external assistance, or an asymptomatic blood glucose measurement <3 mmol/L (<54 mg/dL). Major (or severe) hypoglycaemia: symptomatic events requiring external assistance due to severe impairment in consciousness or behaviour, with or without blood glucose level <3 mmol/L (<54 mg/dL), but with prompt recovery after glucose or glucagon administration. These events may be associated with sufficient neuroglycopenia to induce seizure or coma. Plasma glucose measurements may not be available during such an event, but neurological recovery, attributable to the restoration of plasma glucose to normal, was considered sufficient evidence that the event was induced by a low plasma glucose concentration. Safety analysis set.
Time Frame	From week 0 to week 52.
Safety Issue?	Yes

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Safety analysis set (a subset of the randomised analysis set including patients who took at least one investigational product dose).

Reporting Groups

	Description
Saxagliptin 5 mg	Saxagliptin 5 mg, oral tablet, once daily
Glimepiride 1 - 6 mg	Glimepiride 1, 2, 3, 4 or 6 mg, oral encapsulated tablet, once daily

Measured Values

	Saxagliptin 5 mg	Glimepiride 1 - 6 mg
Number of Participants Analyzed [units:participants]	359	359
Proportion of Patients Having Experienced at Least One Hypoglycaemic Event (Confirmed or Severe) over the 52-week Double-blind Treatment Period. [units: percentage of patients]	1.1	15.3

No statistical analysis provided for Proportion of Patients Having Experienced at Least One Hypoglycaemic Event (Confirmed or Severe) over the 52-week Double-blind Treatment Period.

3. Secondary Outcome Measure: Change from baseline to week 52 in HbA1c. [ Time Frame: From week 0 to week 52. ]

Measure Type	Secondary
Measure Name	Change from baseline to week 52 in HbA1c.
Measure Description	Measured as the difference between the last on-treatment value (defined as obtained before or on the 8th day after the last dosing date), and the last pre-randomisation HbA1c value, as determined by central laboratory. Full analysis set.
Time Frame	From week 0 to week 52.
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The number of subjects with non-missing baseline and Week 52 (LOCF) values in the full analysis set (defined as the subset of patients in the randomized analysis set who took at least one randomised IP dose and have non-missing baseline and post-baseline efficacy data for at least one variable).

Reporting Groups

	Description
Saxagliptin 5 mg	Saxagliptin 5 mg, oral tablet, once daily
Glimepiride 1 - 6 mg	Glimepiride 1, 2, 3, 4 or 6 mg, oral encapsulated tablet, once daily

Measured Values

	Saxagliptin 5 mg	Glimepiride 1 - 6 mg
Number of Participants Analyzed [units:participants]	353	345
Change from baseline to week 52 in HbA1c. [units: % of glycosylated hemoglobin] Mean (95% Confidence Interval)	-0.44 (-0.51 to -0.37)	-0.64 (-0.71 to -0.57)

No statistical analysis provided for Change from baseline to week 52 in HbA1c.

4. Secondary Outcome Measure: Proportion of patients achieving a therapeutic glycaemic response at Week 52 defined as HbA1c <7.0% [ Time Frame: From week 0 to week 52 ]

Measure Type	Secondary
Measure Name	Proportion of patients achieving a therapeutic glycaemic response at Week 52 defined as HbA1c <7.0%
Measure Description	Proportion of patients with their last on-treatment value (defined as obtained before or on the 8th day after the last dosing date), as determined by central laboratory, below the specified limits. Full analysis set.
Time Frame	From week 0 to week 52
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The number of subjects with non-missing baseline and Week 52 (LOCF) values in the full analysis set (defined as the subset of patients in the randomized analysis set who took at least one randomised IP dose and have non-missing baseline and post-baseline efficacy data for at least one variable).

Reporting Groups

	Description
Saxagliptin 5 mg	Saxagliptin 5 mg, oral tablet, once daily
Glimepiride 1 - 6 mg	Glimepiride 1, 2, 3, 4 or 6 mg, oral encapsulated tablet, once daily

Measured Values

	Saxagliptin 5 mg	Glimepiride 1 - 6 mg
Number of Participants Analyzed [units:participants]	356	353
Proportion of patients achieving a therapeutic glycaemic response at Week 52 defined as HbA1c <7.0% [units: percentage of responders]	44.7	54.7

No statistical analysis provided for Proportion of patients achieving a therapeutic glycaemic response at Week 52 defined as HbA1c <7.0%

5. Secondary Outcome Measure: Change from baseline to Week 52 in fasting plasma glucose (FPG) [ Time Frame: From week 0 to week 52 ]

Measure Type	Secondary
Measure Name	Change from baseline to Week 52 in fasting plasma glucose (FPG)
Measure Description	Measured as the difference between the last on-treatment value (defined as obtained before or on the first day after the last dosing date)and the last pre-randomisation fasting plasma glucose value, as determined by central laboratory. Full analysis set.
Time Frame	From week 0 to week 52
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The number of subjects with non-missing baseline and Week 52 (LOCF) values in the full analysis set (defined as the subset of patients in the randomized analysis set who took at least one randomised IP dose and have non-missing baseline and post-baseline efficacy data for at least one variable).

Reporting Groups

	Description
Saxagliptin 5 mg	Saxagliptin 5 mg, oral tablet, once daily
Glimepiride 1 - 6 mg	Glimepiride 1, 2, 3, 4 or 6 mg, oral encapsulated tablet, once daily

Measured Values

	Saxagliptin 5 mg	Glimepiride 1 - 6 mg
Number of Participants Analyzed [units:participants]	344	339
Change from baseline to Week 52 in fasting plasma glucose (FPG) [units: mmol/L] Mean (95% Confidence Interval)	-0.73 (-0.89 to -0.57)	-1.29 (-1.45 to -1.13)

No statistical analysis provided for Change from baseline to Week 52 in fasting plasma glucose (FPG)

6. Secondary Outcome Measure: Change From Baseline to Week 52 in Insulin [ Time Frame: From week 0 to week 52 ]

Measure Type	Secondary
Measure Name	Change From Baseline to Week 52 in Insulin
Measure Description	Measured as the difference between the last on-treatment value (defined as obtained before or on the first day after the last dosing date) and the last pre-randomisation fasting plasma insulin value, as determined by central laboratory. Full analysis set.
Time Frame	From week 0 to week 52
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The number of subjects with non-missing baseline and Week 52 (LOCF) values in the full analysis set (defined as the subset of patients in the randomized analysis set who took at least one randomised IP dose and have non-missing baseline and post-baseline efficacy data for at least one variable).

Reporting Groups

	Description
Saxagliptin 5 mg	Saxagliptin 5 mg, oral tablet, once daily
Glimepiride 1 - 6 mg	Glimepiride 1, 2, 3, 4 or 6 mg, oral encapsulated tablet, once daily

Measured Values

	Saxagliptin 5 mg	Glimepiride 1 - 6 mg
Number of Participants Analyzed [units:participants]	312	309
Change From Baseline to Week 52 in Insulin [units: µU/mL] Mean (95% Confidence Interval)	-2.0 (-3.1 to -1.0)	-0.6 (-1.6 to 0.5)

No statistical analysis provided for Change From Baseline to Week 52 in Insulin

7. Secondary Outcome Measure: Change from baseline to Week 52 in β-cell function (as measured by Homeostasis Model Assessment-β [HOMA-β] [ Time Frame: From week 0 to week 52 ]

Measure Type	Secondary
Measure Name	Change from baseline to Week 52 in β-cell function (as measured by Homeostasis Model Assessment-β [HOMA-β]
Measure Description	β-cell function as estimated by the homeostasis model assessment (HOMA) model. Value is derived from FPG and fasting insulin; fasting insulin values below 2.074 μU/mL or above 57.595 μU/mL and FPG values below 3 mmol/L or above 25 mmol/L are excluded (as restricted by the calculation method used). Full analysis set.
Time Frame	From week 0 to week 52
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The number of subjects with non-missing baseline and Week 52 (LOCF) values in the full analysis set (defined as the subset of patients in the randomized analysis set who took at least one randomised IP dose and have non-missing baseline and post-baseline efficacy data for at least one variable).

Reporting Groups

	Description
Saxagliptin 5 mg	Saxagliptin 5 mg, oral tablet, once daily
Glimepiride 1 - 6 mg	Glimepiride 1, 2, 3, 4 or 6 mg, oral encapsulated tablet, once daily

Measured Values

	Saxagliptin 5 mg	Glimepiride 1 - 6 mg
Number of Participants Analyzed [units:participants]	240	247
Change from baseline to Week 52 in β-cell function (as measured by Homeostasis Model Assessment-β [HOMA-β] [units: percentage of change from baseline] Mean (95% Confidence Interval)	3.83 (0.79 to 6.88)	16.22 (13.23 to 19.20)

No statistical analysis provided for Change from baseline to Week 52 in β-cell function (as measured by Homeostasis Model Assessment-β [HOMA-β]

Serious Adverse Events

Time Frame	No text entered.
Additional Description	The at Risk population includes only those randomized subjects who took at least one dose of study drug.

Reporting Groups

	Description
Saxagliptin 5 mg	Saxagliptin 5 mg, oral tablet, once daily
Glimepiride 1 - 6 mg	Glimepiride 1, 2, 3, 4 or 6 mg, oral encapsulated tablet, once daily

Serious Adverse Events

Saxagliptin 5 mg

Glimepiride 1 - 6 mg

Total, serious adverse events

# participants affected / at risk

41/359 (11.42%)

32/359 (8.91%)

Blood and lymphatic system disorders

ANAEMIA¹,^†

# participants affected / at risk

1/359 (0.28%)

0/359 (0.00%)

Blood and lymphatic system disorders

LYMPHADENOPATHY¹,^†

# participants affected / at risk

0/359 (0.00%)

1/359 (0.28%)

Cardiac disorders

CARDIAC FAILURE¹,^†

# participants affected / at risk

1/359 (0.28%)

3/359 (0.84%)

Cardiac disorders

MYOCARDIAL INFARCTION¹,^†

# participants affected / at risk

3/359 (0.84%)

1/359 (0.28%)

Cardiac disorders

ACUTE MYOCARDIAL INFARCTION¹,^†

# participants affected / at risk

0/359 (0.00%)

2/359 (0.56%)

Cardiac disorders

ATRIAL FIBRILLATION¹,^†

# participants affected / at risk

2/359 (0.56%)

1/359 (0.28%)

Cardiac disorders

ANGINA PECTORIS¹,^†

# participants affected / at risk

1/359 (0.28%)

Cardiac disorders

ANGINA UNSTABLE¹,^†

# participants affected / at risk

1/359 (0.28%)

0/359 (0.00%)

Cardiac disorders

ISCHAEMIC CARDIOMYOPATHY¹,^†

# participants affected / at risk

1/359 (0.28%)

0/359 (0.00%)

Cardiac disorders

PERICARDITIS¹,^†

# participants affected / at risk

1/359 (0.28%)

0/359 (0.00%)

Cardiac disorders

TACHYCARDIA¹,^†

# participants affected / at risk

0/359 (0.00%)

1/359 (0.28%)

Gastrointestinal disorders

EPIGASTRIC DISCOMFORT¹,^†

# participants affected / at risk

1/359 (0.28%)

0/359 (0.00%)

Gastrointestinal disorders

HIATUS HERNIA¹,^†

# participants affected / at risk

1/359 (0.28%)

0/359 (0.00%)

Gastrointestinal disorders

INGUINAL HERNIA¹,^†

# participants affected / at risk

1/359 (0.28%)

0/359 (0.00%)

Gastrointestinal disorders

MELAENA¹,^†

# participants affected / at risk

1/359 (0.28%)

0/359 (0.00%)

Gastrointestinal disorders

SUBILEUS¹,^†

# participants affected / at risk

0/359 (0.00%)

1/359 (0.28%)

General disorders

CHEST PAIN¹,^†

# participants affected / at risk

1/359 (0.28%)

0/359 (0.00%)

General disorders

DEATH¹,^†

# participants affected / at risk

0/359 (0.00%)

1/359 (0.28%)

General disorders

DEVICE DISLOCATION¹,^†

# participants affected / at risk

1/359 (0.28%)

0/359 (0.00%)

General disorders

INFLAMMATION¹,^†

# participants affected / at risk

1/359 (0.28%)

0/359 (0.00%)

Hepatobiliary disorders

CHOLECYSTITIS¹,^†

# participants affected / at risk

1/359 (0.28%)

0/359 (0.00%)

Immune system disorders

ANAPHYLACTIC SHOCK¹,^†

# participants affected / at risk

1/359 (0.28%)

0/359 (0.00%)

Infections and infestations

PNEUMONIA¹,^†

# participants affected / at risk

3/359 (0.84%)

Infections and infestations

APPENDICITIS¹,^†

# participants affected / at risk

1/359 (0.28%)

0/359 (0.00%)

Infections and infestations

DIVERTICULITIS¹,^†

# participants affected / at risk

0/359 (0.00%)

1/359 (0.28%)

Infections and infestations

GASTROENTERITIS¹,^†

# participants affected / at risk

0/359 (0.00%)

1/359 (0.28%)

Infections and infestations

GASTROENTERITIS NOROVIRUS¹,^†

# participants affected / at risk

0/359 (0.00%)

1/359 (0.28%)

Infections and infestations

INFECTIOUS PLEURAL EFFUSION¹,^†

# participants affected / at risk

0/359 (0.00%)

1/359 (0.28%)

Infections and infestations

LABYRINTHITIS¹,^†

# participants affected / at risk

0/359 (0.00%)

1/359 (0.28%)

Infections and infestations

PYELONEPHRITIS¹,^†

# participants affected / at risk

1/359 (0.28%)

0/359 (0.00%)

Infections and infestations

RESPIRATORY TRACT INFECTION¹,^†

# participants affected / at risk

0/359 (0.00%)

1/359 (0.28%)

Infections and infestations

URINARY TRACT INFECTION¹,^†

# participants affected / at risk

0/359 (0.00%)

1/359 (0.28%)

Infections and infestations

UROSEPSIS¹,^†

# participants affected / at risk

1/359 (0.28%)

0/359 (0.00%)

Injury, poisoning and procedural complications

LUMBAR VERTEBRAL FRACTURE¹,^†

# participants affected / at risk

2/359 (0.56%)

0/359 (0.00%)

Injury, poisoning and procedural complications

ANKLE FRACTURE¹,^†

# participants affected / at risk

0/359 (0.00%)

1/359 (0.28%)

Injury, poisoning and procedural complications

CONCUSSION¹,^†

# participants affected / at risk

1/359 (0.28%)

0/359 (0.00%)

Injury, poisoning and procedural complications

CONTUSION¹,^†

# participants affected / at risk

0/359 (0.00%)

1/359 (0.28%)

Injury, poisoning and procedural complications

FEMUR FRACTURE¹,^†

# participants affected / at risk

1/359 (0.28%)

0/359 (0.00%)

Injury, poisoning and procedural complications

HAND FRACTURE¹,^†

# participants affected / at risk

1/359 (0.28%)

0/359 (0.00%)

Injury, poisoning and procedural complications

MUSCLE RUPTURE¹,^†

# participants affected / at risk

0/359 (0.00%)

1/359 (0.28%)

Investigations

MEDICAL OBSERVATION¹,^†

# participants affected / at risk

0/359 (0.00%)

1/359 (0.28%)

Investigations

WEIGHT DECREASED¹,^†

# participants affected / at risk

1/359 (0.28%)

0/359 (0.00%)

Metabolism and nutrition disorders

HYPERKALAEMIA¹,^†

# participants affected / at risk

1/359 (0.28%)

0/359 (0.00%)

Metabolism and nutrition disorders

HYPOGLYCAEMIA¹,^†

# participants affected / at risk

0/359 (0.00%)

1/359 (0.28%)

Musculoskeletal and connective tissue disorders

ARTHRALGIA¹,^†

# participants affected / at risk

1/359 (0.28%)

0/359 (0.00%)

Musculoskeletal and connective tissue disorders

BACK PAIN¹,^†

# participants affected / at risk

1/359 (0.28%)

0/359 (0.00%)

Musculoskeletal and connective tissue disorders

INTERVERTEBRAL DISC PROTRUSION¹,^†

# participants affected / at risk

0/359 (0.00%)

1/359 (0.28%)

Musculoskeletal and connective tissue disorders

JOINT EFFUSION¹,^†

# participants affected / at risk

0/359 (0.00%)

1/359 (0.28%)

Musculoskeletal and connective tissue disorders

OSTEOARTHRITIS¹,^†

# participants affected / at risk

1/359 (0.28%)

0/359 (0.00%)

Musculoskeletal and connective tissue disorders

SPINAL COLUMN STENOSIS¹,^†

# participants affected / at risk

1/359 (0.28%)

0/359 (0.00%)

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

BREAST CANCER¹,^†

# participants affected / at risk

2/359 (0.56%)

0/359 (0.00%)

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

BASAL CELL CARCINOMA¹,^†

# participants affected / at risk

1/359 (0.28%)

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

BLADDER TRANSITIONAL CELL CARCINOMA¹,^†

# participants affected / at risk

1/359 (0.28%)

0/359 (0.00%)

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

BREAST CANCER IN SITU¹,^†

# participants affected / at risk

1/359 (0.28%)

0/359 (0.00%)

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

COLON CANCER¹,^†

# participants affected / at risk

1/359 (0.28%)

0/359 (0.00%)

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

HEPATIC NEOPLASM MALIGNANT¹,^†

# participants affected / at risk

1/359 (0.28%)

0/359 (0.00%)

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

LUNG CANCER METASTATIC¹,^†

# participants affected / at risk

0/359 (0.00%)

1/359 (0.28%)

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

LYMPHOMA¹,^†

# participants affected / at risk

1/359 (0.28%)

0/359 (0.00%)

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

PANCREATIC CARCINOMA¹,^†

# participants affected / at risk

1/359 (0.28%)

0/359 (0.00%)

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

PROSTATE CANCER¹,^†

# participants affected / at risk

0/359 (0.00%)

1/359 (0.28%)

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

SALIVARY GLAND CANCER¹,^†

# participants affected / at risk

1/359 (0.28%)

0/359 (0.00%)

Nervous system disorders

CEREBROVASCULAR ACCIDENT¹,^†

# participants affected / at risk

0/359 (0.00%)

1/359 (0.28%)

Nervous system disorders

EPILEPSY¹,^†

# participants affected / at risk

0/359 (0.00%)

1/359 (0.28%)

Nervous system disorders

SYNCOPE¹,^†

# participants affected / at risk

1/359 (0.28%)

Nervous system disorders

TRANSIENT ISCHAEMIC ATTACK¹,^†

# participants affected / at risk

0/359 (0.00%)

1/359 (0.28%)

Renal and urinary disorders

CALCULUS BLADDER¹,^†

# participants affected / at risk

1/359 (0.28%)

0/359 (0.00%)

Renal and urinary disorders

CALCULUS URETERIC¹,^†

# participants affected / at risk

0/359 (0.00%)

1/359 (0.28%)

Renal and urinary disorders

NEUROGENIC BLADDER¹,^†

# participants affected / at risk

0/359 (0.00%)

1/359 (0.28%)

Respiratory, thoracic and mediastinal disorders

CHRONIC OBSTRUCTIVE PULMONARY DISEASE¹,^†

# participants affected / at risk

1/359 (0.28%)

Respiratory, thoracic and mediastinal disorders

DYSPNOEA¹,^†

# participants affected / at risk

0/359 (0.00%)

1/359 (0.28%)

Surgical and medical procedures

SURGICAL AND MEDICAL PROCEDURES CARDIOVERSION Systematic Assessment 0 359 1 359¹,^†

# participants affected / at risk

1/359 (0.28%)

0/359 (0.00%)

Vascular disorders

AORTIC ANEURYSM¹,^†

# participants affected / at risk

1/359 (0.28%)

0/359 (0.00%)

Vascular disorders

AORTIC ARTERIOSCLEROSIS¹,^†

# participants affected / at risk

0/359 (0.00%)

1/359 (0.28%)

Vascular disorders

CIRCULATORY COLLAPSE¹,^†

# participants affected / at risk

0/359 (0.00%)

1/359 (0.28%)

Vascular disorders

PERIPHERAL ARTERIAL OCCLUSIVE DISEASE¹,^†

# participants affected / at risk

1/359 (0.28%)

0/359 (0.00%)

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA 15.0
2	Term from vocabulary,

Other Adverse Events

Time Frame	No text entered.
Additional Description	The at Risk population includes only those randomized subjects who took at least one dose of study drug.

Frequency Threshold

Threshold above which other adverse events are reported	2%

Reporting Groups

	Description
Saxagliptin 5 mg	Saxagliptin 5 mg, oral tablet, once daily
Glimepiride 1 - 6 mg	Glimepiride 1, 2, 3, 4 or 6 mg, oral encapsulated tablet, once daily

Other Adverse Events

Saxagliptin 5 mg

Glimepiride 1 - 6 mg

Total, other (not including serious) adverse events

# participants affected / at risk

130/359 (36.21%)

129/359 (35.93%)

Ear and labyrinth disorders

VERTIGO¹,^†

# participants affected / at risk

9/359 (2.51%)

0/359 (0.00%)

Gastrointestinal disorders

DIARRHOEA¹,^†

# participants affected / at risk

15/359 (4.18%)

19/359 (5.29%)

Gastrointestinal disorders

CONSTIPATION¹,^†

# participants affected / at risk

4/359 (1.11%)

10/359 (2.79%)

Gastrointestinal disorders

NAUSEA¹,^†

# participants affected / at risk

4/359 (1.11%)

8/359 (2.23%)

Infections and infestations

NASOPHARYNGITIS¹,^†

# participants affected / at risk

23/359 (6.41%)

35/359 (9.75%)

Infections and infestations

URINARY TRACT INFECTION¹,^†

# participants affected / at risk

11/359 (3.06%)

18/359 (5.01%)

Infections and infestations

BRONCHITIS¹,^†

# participants affected / at risk

14/359 (3.90%)

7/359 (1.95%)

Infections and infestations

UPPER RESPIRATORY TRACT INFECTION¹,^†

# participants affected / at risk

12/359 (3.34%)

14/359 (3.90%)

Injury, poisoning and procedural complications

CONTUSION¹,^†

# participants affected / at risk

8/359 (2.23%)

0/359 (0.00%)

Musculoskeletal and connective tissue disorders

BACK PAIN¹,^†

# participants affected / at risk

9/359 (2.51%)

18/359 (5.01%)

Musculoskeletal and connective tissue disorders

ARTHRALGIA¹,^†

# participants affected / at risk

17/359 (4.74%)

9/359 (2.51%)

Musculoskeletal and connective tissue disorders

PAIN IN EXTREMITY¹,^†

# participants affected / at risk

10/359 (2.79%)

9/359 (2.51%)

Musculoskeletal and connective tissue disorders

MUSCULOSKELETAL PAIN¹,^†

# participants affected / at risk

9/359 (2.51%)

3/359 (0.84%)

Nervous system disorders

DIZZINESS¹,^†

# participants affected / at risk

6/359 (1.67%)

17/359 (4.74%)

Nervous system disorders

HEADACHE¹,^†

# participants affected / at risk

6/359 (1.67%)

12/359 (3.34%)

Nervous system disorders

TREMOR¹,^†

# participants affected / at risk

1/359 (0.28%)

8/359 (2.23%)

Respiratory, thoracic and mediastinal disorders

COUGH¹,^†

# participants affected / at risk

9/359 (2.51%)

13/359 (3.62%)

Vascular disorders

HYPERTENSION¹,^†

# participants affected / at risk

8/359 (2.23%)

12/359 (3.34%)

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA 15.0
2	Term from vocabulary,

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

The agreement is:

	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days . The sponsor cannot require changes to the communication and cannot extend the embargo.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed. Restriction Description: No publication or presentation may include any of AZ’s confidential information without AZ’s prior written approval.

Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.

Results Point of Contact

Name/Title:	Boaz Hirshberg , MSD
Organization:	AstraZeneca
E-mail:	[email protected]

Documents available

CSR-D1680L00002.pdf
Download
D1680L00002_Clinical_Study_Protocol
Download
Trial Results Summaries
Available here

Contacts

Contact

Leif Lohm

+46 8 553 260 00

leif.lohm@astrazeneca.com

Sponsors

Collaborators

Inclusion Criteria

Exclusion Criteria

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

CSR-D1680L00002.pdf

D1680L00002_Clinical_Study_Protocol

Trial Results Summaries