Trial Outcomes & Findings for Mechanistic Evaluation of Glucose-lowering Strategies in Patients With Heart Failure (NCT NCT02917031)

NCT ID: NCT02917031

Last Updated: 2021-11-08

Results Overview

MRI was performed to evaluate LVEDV at baseline and Visit 10 (Week 24). Evaluated to exclude an increase in left ventricular end diastolic volume (LVEDV) index of greater than 10% of the overall baseline value (noninferiority margin) in patients with T2DM and HF treated with saxagliptin for 24 weeks, compared to placebo. Baseline is last assessment on or before the date of first dose.

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 348 participants
• Primary outcome timeframe: Baseline to 24 weeks
• Results posted on: 2021-11-08

Participant Flow

Participants who met all the inclusion and exclusion criteria were enrolled in 9 countries.

Participants with documented Ejection Fraction ≤ 45% and NTproBNP > 300 pg/mL had eligibility criteria assessed within 28 days of screening period. Informed consent was obtained prior to any study-related procedures or dosing of IP. 1 subject was excluded from the FAS as incorrectly randomized. This subject was terminated from the study on the day of randomization and no investigational product was dispensed.

Participant milestones

Measure	Saxagliptin Participants with an eGFR ≥50 mL/min/1.73m\^2 received one saxagliptin 5 mg tablet and one sitaglipitin placebo capsule administered orally once daily for a 24-week treatment period. Participants with an eGFR ≥30 to \<50 mL/min/1.73m\^2, the dose of saxagliptin was adjusted to one 2.5 mg tablet.	Sitagliptin Participants with an eGFR ≥50 mL/min/1.73m\^2 received one sitagliptin 100 mg capsule and one saxagliptin placebo tablet administered orally once daily for a 24-week treatment period. Participants with an eGFR ≥30 to \<50 mL/min/1.73m\^2, the dose of sitagliptin was adjusted to one 50 mg capsule.	Placebo Participants recieved one saxagliptin placebo tablet and one sitagliptin placebo capsule administered orally once daily for a 24-week treatment period as a control.
Overall Study STARTED	112	115	120
Overall Study COMPLETED	94	102	105
Overall Study NOT COMPLETED	18	13	15

Reasons for withdrawal

Measure	Saxagliptin Participants with an eGFR ≥50 mL/min/1.73m\^2 received one saxagliptin 5 mg tablet and one sitaglipitin placebo capsule administered orally once daily for a 24-week treatment period. Participants with an eGFR ≥30 to \<50 mL/min/1.73m\^2, the dose of saxagliptin was adjusted to one 2.5 mg tablet.	Sitagliptin Participants with an eGFR ≥50 mL/min/1.73m\^2 received one sitagliptin 100 mg capsule and one saxagliptin placebo tablet administered orally once daily for a 24-week treatment period. Participants with an eGFR ≥30 to \<50 mL/min/1.73m\^2, the dose of sitagliptin was adjusted to one 50 mg capsule.	Placebo Participants recieved one saxagliptin placebo tablet and one sitagliptin placebo capsule administered orally once daily for a 24-week treatment period as a control.
Overall Study Reason not specified	7	5	6
Overall Study Development of study-specific withdrawal criteria	1	1	0
Overall Study Withdrawal by Subject	3	3	0
Overall Study Physician Decision	1	0	0
Overall Study Adverse Event	4	1	5
Overall Study Death	2	3	4

Baseline Characteristics

Mechanistic Evaluation of Glucose-lowering Strategies in Patients With Heart Failure

Baseline characteristics by cohort

Measure	Saxagliptin n=112 Participants Participants with an eGFR ≥50 mL/min/1.73m\^2 received one saxagliptin 5 mg tablet and one sitaglipitin placebo capsule administered orally once daily for a 24-week treatment period. Participants with an eGFR ≥30 to \<50 mL/min/1.73m\^2, the dose of saxagliptin was adjusted to one 2.5 mg tablet.	Sitagliptin n=115 Participants Participants with an eGFR ≥50 mL/min/1.73m\^2 received one sitagliptin 100 mg capsule and one saxagliptin placebo tablet administered orally once daily for a 24-week treatment period. Participants with an eGFR ≥30 to \<50 mL/min/1.73m\^2, the dose of sitagliptin was adjusted to one 50 mg capsule.	Placebo n=120 Participants Participants recieved one saxagliptin placebo tablet and one sitagliptin placebo capsule administered orally once daily for a 24-week treatment period as a control.	Total n=347 Participants Total of all reporting groups
Age, Continuous	64.6 Years STANDARD_DEVIATION 7.96 • n=5 Participants	64.9 Years STANDARD_DEVIATION 9.85 • n=7 Participants	66.5 Years STANDARD_DEVIATION 7.84 • n=5 Participants	65.4 Years STANDARD_DEVIATION 8.61 • n=4 Participants
Sex: Female, Male Female	35 Participants n=5 Participants	36 Participants n=7 Participants	37 Participants n=5 Participants	108 Participants n=4 Participants
Sex: Female, Male Male	77 Participants n=5 Participants	79 Participants n=7 Participants	83 Participants n=5 Participants	239 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	10 Participants n=5 Participants	16 Participants n=7 Participants	17 Participants n=5 Participants	43 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	102 Participants n=5 Participants	99 Participants n=7 Participants	103 Participants n=5 Participants	304 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Asian	17 Participants n=5 Participants	17 Participants n=7 Participants	15 Participants n=5 Participants	49 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants	0 Participants n=7 Participants	3 Participants n=5 Participants	4 Participants n=4 Participants
Race (NIH/OMB) White	94 Participants n=5 Participants	98 Participants n=7 Participants	102 Participants n=5 Participants	294 Participants n=4 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants

PRIMARY outcome

Timeframe: Baseline to 24 weeks

Population: Full analysis set (FAS): All randomised patients who took at least one dose of the study medication. Here, overall number of participants analyzed presents only those participants who were analyzed for this particular outcome measure.

MRI was performed to evaluate LVEDV at baseline and Visit 10 (Week 24). Evaluated to exclude an increase in left ventricular end diastolic volume (LVEDV) index of greater than 10% of the overall baseline value (noninferiority margin) in patients with T2DM and HF treated with saxagliptin for 24 weeks, compared to placebo. Baseline is last assessment on or before the date of first dose.

Outcome measures

Measure	Saxagliptin n=96 Participants Participants with an eGFR ≥50 mL/min/1.73m\^2 received one saxagliptin 5 mg tablet and one sitaglipitin placebo capsule administered orally once daily for a 24-week treatment period. Participants with an eGFR ≥30 to \<50 mL/min/1.73m\^2, the dose of saxagliptin was adjusted to one 2.5 mg tablet.	Placebo n=106 Participants Participants recieved one saxagliptin placebo tablet and one sitagliptin placebo capsule administered orally once daily for a 24-week treatment period as a control.	Placebo Participants recieved one saxagliptin placebo tablet and one sitagliptin placebo capsule administered orally once daily for a 24-week treatment period as a control.
Change From Baseline in Left Ventricular End Diastolic Volume (LVEDV) Index Measured by Magnetic Resonance Imaging (MRI) at 24 Weeks	-3.395 mL/m^2 Standard Deviation 15.3412	-0.716 mL/m^2 Standard Deviation 18.1178	—

SECONDARY outcome

Timeframe: Baseline to week 24

Population: FAS: All randomised patients who took at least one dose of the study medication. Here, overall number of participants analysed presents only those participants who were analyzed for this particular outcome measure.

Evaluation of the effects of saxagliptin compared to placebo on left ventricular end systolic volume (LVESV) index, after 24 weeks in patients with T2DM and HF.

Outcome measures

Measure	Saxagliptin n=96 Participants Participants with an eGFR ≥50 mL/min/1.73m\^2 received one saxagliptin 5 mg tablet and one sitaglipitin placebo capsule administered orally once daily for a 24-week treatment period. Participants with an eGFR ≥30 to \<50 mL/min/1.73m\^2, the dose of saxagliptin was adjusted to one 2.5 mg tablet.	Placebo n=106 Participants Participants recieved one saxagliptin placebo tablet and one sitagliptin placebo capsule administered orally once daily for a 24-week treatment period as a control.	Placebo Participants recieved one saxagliptin placebo tablet and one sitagliptin placebo capsule administered orally once daily for a 24-week treatment period as a control.
Change From Baseline in Left Ventricular End Systolic Volume (LVESV) Index, Measured by MRI at 24 Weeks.	-2.555 mL/m2 Standard Deviation 12.4136	-0.839 mL/m2 Standard Deviation 17.2458	—

SECONDARY outcome

Timeframe: Baseline to week 24

Population: Full analysis set (FAS): All randomised patients who took at least one dose of the study medication. Here, overall number of participants analysed presents only those participants who were analyzed for this particular outcome measure.

Evaluation the effects of saxagliptin compared to placebo on left ventricular end systolic volume (LVESV) index, left ventricular ejection fraction (LVEF), and left ventricular mass (LVM) after 24 weeks in patients with T2DM and HF.

Outcome measures

Measure	Saxagliptin n=96 Participants Participants with an eGFR ≥50 mL/min/1.73m\^2 received one saxagliptin 5 mg tablet and one sitaglipitin placebo capsule administered orally once daily for a 24-week treatment period. Participants with an eGFR ≥30 to \<50 mL/min/1.73m\^2, the dose of saxagliptin was adjusted to one 2.5 mg tablet.	Placebo n=106 Participants Participants recieved one saxagliptin placebo tablet and one sitagliptin placebo capsule administered orally once daily for a 24-week treatment period as a control.	Placebo Participants recieved one saxagliptin placebo tablet and one sitagliptin placebo capsule administered orally once daily for a 24-week treatment period as a control.
Change From Baseline in Left Ventricular Ejection Fraction (LVEF) Measured by MRI at 24 Weeks.	0.533 Percentage Standard Deviation 7.1971	0.298 Percentage Standard Deviation 7.2843	—

SECONDARY outcome

Timeframe: At 24 week

Population: FAS: All randomised patients who took at least one dose of the study medication. Here, overall number of participants analysed presents only those participants who were analyzed for this particular outcome measure.

Evaluation of the effects of saxagliptin compared to placebo on left ventricular mass (LVM) after 24 weeks in patients with T2DM and HF.

Outcome measures

Measure	Saxagliptin n=96 Participants Participants with an eGFR ≥50 mL/min/1.73m\^2 received one saxagliptin 5 mg tablet and one sitaglipitin placebo capsule administered orally once daily for a 24-week treatment period. Participants with an eGFR ≥30 to \<50 mL/min/1.73m\^2, the dose of saxagliptin was adjusted to one 2.5 mg tablet.	Placebo n=106 Participants Participants recieved one saxagliptin placebo tablet and one sitagliptin placebo capsule administered orally once daily for a 24-week treatment period as a control.	Placebo Participants recieved one saxagliptin placebo tablet and one sitagliptin placebo capsule administered orally once daily for a 24-week treatment period as a control.
Change From Baseline in Left Ventricular Mass (LVM) Measured by MRI at 24 Weeks.	-4.211 Gram Standard Deviation 16.6003	-0.758 Gram Standard Deviation 16.1763	—

SECONDARY outcome

Timeframe: Baseline to Week 28 (End of Study visit [EoS])

Population: FAS: All randomised patients who took at least one dose of the study medication. Here, overall number of participants analysed presents only those participants who were analyzed for this particular outcome measure.

Evaluation of the effects of saxagliptin compared to placebo on N-terminal prohormone of brain natriuretic peptide (NT-proBNP) after 24 weeks of treatment.

Outcome measures

Measure	Saxagliptin n=93 Participants Participants with an eGFR ≥50 mL/min/1.73m\^2 received one saxagliptin 5 mg tablet and one sitaglipitin placebo capsule administered orally once daily for a 24-week treatment period. Participants with an eGFR ≥30 to \<50 mL/min/1.73m\^2, the dose of saxagliptin was adjusted to one 2.5 mg tablet.	Placebo n=104 Participants Participants recieved one saxagliptin placebo tablet and one sitagliptin placebo capsule administered orally once daily for a 24-week treatment period as a control.	Placebo Participants recieved one saxagliptin placebo tablet and one sitagliptin placebo capsule administered orally once daily for a 24-week treatment period as a control.
Change From Baseline in NT-proBNP After 24 Weeks of Treatment	-277.525 pg/mL Standard Deviation 1324.7471	-61.895 pg/mL Standard Deviation 3415.9525	—

SECONDARY outcome

Timeframe: From screening (Days -28 to -1) until Week 28 (follow-up visit)

Population: Safety analysis set (SAS): All randomised patients who took at least one dose of the study medication.

Assessment of safety and tolerability of saxagliptin and sitagliptin treatment in patients with T2DM and HF

Outcome measures

Measure	Saxagliptin n=112 Participants Participants with an eGFR ≥50 mL/min/1.73m\^2 received one saxagliptin 5 mg tablet and one sitaglipitin placebo capsule administered orally once daily for a 24-week treatment period. Participants with an eGFR ≥30 to \<50 mL/min/1.73m\^2, the dose of saxagliptin was adjusted to one 2.5 mg tablet.	Placebo n=115 Participants Participants recieved one saxagliptin placebo tablet and one sitagliptin placebo capsule administered orally once daily for a 24-week treatment period as a control.	Placebo n=120 Participants Participants recieved one saxagliptin placebo tablet and one sitagliptin placebo capsule administered orally once daily for a 24-week treatment period as a control.
Number of Participants With Adverse Events Any severe AE	9 Participants	13 Participants	14 Participants
Number of Participants With Adverse Events Any SAE leading to discontinuation of study treatment	1 Participants	0 Participants	4 Participants
Number of Participants With Adverse Events Any AE	53 Participants	51 Participants	58 Participants
Number of Participants With Adverse Events Any treatment related AE	3 Participants	4 Participants	0 Participants
Number of Participants With Adverse Events Any AE with outcome Death	2 Participants	3 Participants	4 Participants
Number of Participants With Adverse Events Any SAE	17 Participants	19 Participants	29 Participants
Number of Participants With Adverse Events Any treatment related SAE	0 Participants	0 Participants	0 Participants
Number of Participants With Adverse Events Any AE leading to discontinuation of study treatment	5 Participants	3 Participants	7 Participants
Number of Participants With Adverse Events Any Adverse event of special interest	12 Participants	15 Participants	16 Participants

Adverse Events

Saxagliptin

Serious events: 17 serious events

Other events: 8 other events

Deaths: 2 deaths

Sitagliptin

Serious events: 19 serious events

Other events: 9 other events

Deaths: 3 deaths

Placebo

Serious events: 29 serious events

Other events: 8 other events

Deaths: 4 deaths

Serious adverse events

Measure	Saxagliptin n=112 participants at risk Participants with an eGFR ≥50 mL/min/1.73m\^2 received one saxagliptin 5 mg tablet and one sitaglipitin placebo capsule administered orally once daily for a 24-week treatment period. Participants with an eGFR ≥30 to \<50 mL/min/1.73m\^2, the dose of saxagliptin was adjusted to one 2.5 mg tablet.	Sitagliptin n=115 participants at risk Participants with an eGFR ≥50 mL/min/1.73m\^2 received one sitagliptin 100 mg capsule and one saxagliptin placebo tablet administered orally once daily for a 24-week treatment period. Participants with an eGFR ≥30 to \<50 mL/min/1.73m\^2, the dose of sitagliptin was adjusted to one 50 mg capsule.	Placebo n=120 participants at risk Participants recieved one saxagliptin placebo tablet and one sitagliptin placebo capsule administered orally once daily for a 24-week treatment period as a control.
Cardiac disorders Cardiac failure	6.2% 7/112 • From screening (Days -28 to -1) until Week 28 (follow-up visit) An AEs is the development of an undesirable medical condition or the deterioration of a preexisting medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product.	4.3% 5/115 • From screening (Days -28 to -1) until Week 28 (follow-up visit) An AEs is the development of an undesirable medical condition or the deterioration of a preexisting medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product.	5.0% 6/120 • From screening (Days -28 to -1) until Week 28 (follow-up visit) An AEs is the development of an undesirable medical condition or the deterioration of a preexisting medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product.
Cardiac disorders Acute coronary syndrome	0.89% 1/112 • From screening (Days -28 to -1) until Week 28 (follow-up visit) An AEs is the development of an undesirable medical condition or the deterioration of a preexisting medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product.	0.87% 1/115 • From screening (Days -28 to -1) until Week 28 (follow-up visit) An AEs is the development of an undesirable medical condition or the deterioration of a preexisting medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product.	0.00% 0/120 • From screening (Days -28 to -1) until Week 28 (follow-up visit) An AEs is the development of an undesirable medical condition or the deterioration of a preexisting medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product.
Cardiac disorders Angina unstable	0.00% 0/112 • From screening (Days -28 to -1) until Week 28 (follow-up visit) An AEs is the development of an undesirable medical condition or the deterioration of a preexisting medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product.	0.00% 0/115 • From screening (Days -28 to -1) until Week 28 (follow-up visit) An AEs is the development of an undesirable medical condition or the deterioration of a preexisting medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product.	1.7% 2/120 • From screening (Days -28 to -1) until Week 28 (follow-up visit) An AEs is the development of an undesirable medical condition or the deterioration of a preexisting medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product.
Cardiac disorders Atrial fibrillation	0.00% 0/112 • From screening (Days -28 to -1) until Week 28 (follow-up visit) An AEs is the development of an undesirable medical condition or the deterioration of a preexisting medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product.	0.87% 1/115 • From screening (Days -28 to -1) until Week 28 (follow-up visit) An AEs is the development of an undesirable medical condition or the deterioration of a preexisting medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product.	0.83% 1/120 • From screening (Days -28 to -1) until Week 28 (follow-up visit) An AEs is the development of an undesirable medical condition or the deterioration of a preexisting medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product.
Cardiac disorders Acute left ventricular failure	0.00% 0/112 • From screening (Days -28 to -1) until Week 28 (follow-up visit) An AEs is the development of an undesirable medical condition or the deterioration of a preexisting medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product.	0.87% 1/115 • From screening (Days -28 to -1) until Week 28 (follow-up visit) An AEs is the development of an undesirable medical condition or the deterioration of a preexisting medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product.	0.00% 0/120 • From screening (Days -28 to -1) until Week 28 (follow-up visit) An AEs is the development of an undesirable medical condition or the deterioration of a preexisting medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product.
Cardiac disorders Acute myocardial infarction	0.00% 0/112 • From screening (Days -28 to -1) until Week 28 (follow-up visit) An AEs is the development of an undesirable medical condition or the deterioration of a preexisting medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product.	0.87% 1/115 • From screening (Days -28 to -1) until Week 28 (follow-up visit) An AEs is the development of an undesirable medical condition or the deterioration of a preexisting medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product.	0.00% 0/120 • From screening (Days -28 to -1) until Week 28 (follow-up visit) An AEs is the development of an undesirable medical condition or the deterioration of a preexisting medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product.
Cardiac disorders Angina pectoris	0.00% 0/112 • From screening (Days -28 to -1) until Week 28 (follow-up visit) An AEs is the development of an undesirable medical condition or the deterioration of a preexisting medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product.	0.00% 0/115 • From screening (Days -28 to -1) until Week 28 (follow-up visit) An AEs is the development of an undesirable medical condition or the deterioration of a preexisting medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product.	0.83% 1/120 • From screening (Days -28 to -1) until Week 28 (follow-up visit) An AEs is the development of an undesirable medical condition or the deterioration of a preexisting medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product.
Cardiac disorders Bradycardia	0.00% 0/112 • From screening (Days -28 to -1) until Week 28 (follow-up visit) An AEs is the development of an undesirable medical condition or the deterioration of a preexisting medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product.	0.00% 0/115 • From screening (Days -28 to -1) until Week 28 (follow-up visit) An AEs is the development of an undesirable medical condition or the deterioration of a preexisting medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product.	0.83% 1/120 • From screening (Days -28 to -1) until Week 28 (follow-up visit) An AEs is the development of an undesirable medical condition or the deterioration of a preexisting medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product.
Cardiac disorders Cardiac failure acute	0.00% 0/112 • From screening (Days -28 to -1) until Week 28 (follow-up visit) An AEs is the development of an undesirable medical condition or the deterioration of a preexisting medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product.	0.87% 1/115 • From screening (Days -28 to -1) until Week 28 (follow-up visit) An AEs is the development of an undesirable medical condition or the deterioration of a preexisting medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product.	0.00% 0/120 • From screening (Days -28 to -1) until Week 28 (follow-up visit) An AEs is the development of an undesirable medical condition or the deterioration of a preexisting medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product.
Cardiac disorders Coronary artery disease	0.89% 1/112 • From screening (Days -28 to -1) until Week 28 (follow-up visit) An AEs is the development of an undesirable medical condition or the deterioration of a preexisting medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product.	0.00% 0/115 • From screening (Days -28 to -1) until Week 28 (follow-up visit) An AEs is the development of an undesirable medical condition or the deterioration of a preexisting medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product.	0.00% 0/120 • From screening (Days -28 to -1) until Week 28 (follow-up visit) An AEs is the development of an undesirable medical condition or the deterioration of a preexisting medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product.
Cardiac disorders Supraventricular tachycardia	0.89% 1/112 • From screening (Days -28 to -1) until Week 28 (follow-up visit) An AEs is the development of an undesirable medical condition or the deterioration of a preexisting medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product.	0.00% 0/115 • From screening (Days -28 to -1) until Week 28 (follow-up visit) An AEs is the development of an undesirable medical condition or the deterioration of a preexisting medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product.	0.00% 0/120 • From screening (Days -28 to -1) until Week 28 (follow-up visit) An AEs is the development of an undesirable medical condition or the deterioration of a preexisting medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product.
Cardiac disorders Ventricular tachycardia	0.00% 0/112 • From screening (Days -28 to -1) until Week 28 (follow-up visit) An AEs is the development of an undesirable medical condition or the deterioration of a preexisting medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product.	0.87% 1/115 • From screening (Days -28 to -1) until Week 28 (follow-up visit) An AEs is the development of an undesirable medical condition or the deterioration of a preexisting medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product.	0.00% 0/120 • From screening (Days -28 to -1) until Week 28 (follow-up visit) An AEs is the development of an undesirable medical condition or the deterioration of a preexisting medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product.
Infections and infestations Pneumonia	2.7% 3/112 • From screening (Days -28 to -1) until Week 28 (follow-up visit) An AEs is the development of an undesirable medical condition or the deterioration of a preexisting medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product.	0.87% 1/115 • From screening (Days -28 to -1) until Week 28 (follow-up visit) An AEs is the development of an undesirable medical condition or the deterioration of a preexisting medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product.	0.83% 1/120 • From screening (Days -28 to -1) until Week 28 (follow-up visit) An AEs is the development of an undesirable medical condition or the deterioration of a preexisting medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product.
Infections and infestations Acute hepatitis B	0.00% 0/112 • From screening (Days -28 to -1) until Week 28 (follow-up visit) An AEs is the development of an undesirable medical condition or the deterioration of a preexisting medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product.	0.00% 0/115 • From screening (Days -28 to -1) until Week 28 (follow-up visit) An AEs is the development of an undesirable medical condition or the deterioration of a preexisting medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product.	0.83% 1/120 • From screening (Days -28 to -1) until Week 28 (follow-up visit) An AEs is the development of an undesirable medical condition or the deterioration of a preexisting medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product.
Infections and infestations Epididymitis	0.89% 1/112 • From screening (Days -28 to -1) until Week 28 (follow-up visit) An AEs is the development of an undesirable medical condition or the deterioration of a preexisting medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product.	0.00% 0/115 • From screening (Days -28 to -1) until Week 28 (follow-up visit) An AEs is the development of an undesirable medical condition or the deterioration of a preexisting medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product.	0.00% 0/120 • From screening (Days -28 to -1) until Week 28 (follow-up visit) An AEs is the development of an undesirable medical condition or the deterioration of a preexisting medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product.
Infections and infestations Laryngitis	0.00% 0/112 • From screening (Days -28 to -1) until Week 28 (follow-up visit) An AEs is the development of an undesirable medical condition or the deterioration of a preexisting medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product.	0.00% 0/115 • From screening (Days -28 to -1) until Week 28 (follow-up visit) An AEs is the development of an undesirable medical condition or the deterioration of a preexisting medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product.	0.83% 1/120 • From screening (Days -28 to -1) until Week 28 (follow-up visit) An AEs is the development of an undesirable medical condition or the deterioration of a preexisting medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product.
Infections and infestations Sepsis	0.00% 0/112 • From screening (Days -28 to -1) until Week 28 (follow-up visit) An AEs is the development of an undesirable medical condition or the deterioration of a preexisting medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product.	0.00% 0/115 • From screening (Days -28 to -1) until Week 28 (follow-up visit) An AEs is the development of an undesirable medical condition or the deterioration of a preexisting medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product.	0.83% 1/120 • From screening (Days -28 to -1) until Week 28 (follow-up visit) An AEs is the development of an undesirable medical condition or the deterioration of a preexisting medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product.
Injury, poisoning and procedural complications Ankle fracture	0.00% 0/112 • From screening (Days -28 to -1) until Week 28 (follow-up visit) An AEs is the development of an undesirable medical condition or the deterioration of a preexisting medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product.	0.00% 0/115 • From screening (Days -28 to -1) until Week 28 (follow-up visit) An AEs is the development of an undesirable medical condition or the deterioration of a preexisting medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product.	0.83% 1/120 • From screening (Days -28 to -1) until Week 28 (follow-up visit) An AEs is the development of an undesirable medical condition or the deterioration of a preexisting medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product.
Injury, poisoning and procedural complications Craniocerebral injury	0.00% 0/112 • From screening (Days -28 to -1) until Week 28 (follow-up visit) An AEs is the development of an undesirable medical condition or the deterioration of a preexisting medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product.	0.00% 0/115 • From screening (Days -28 to -1) until Week 28 (follow-up visit) An AEs is the development of an undesirable medical condition or the deterioration of a preexisting medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product.	0.83% 1/120 • From screening (Days -28 to -1) until Week 28 (follow-up visit) An AEs is the development of an undesirable medical condition or the deterioration of a preexisting medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product.
Injury, poisoning and procedural complications Femur fracture	0.00% 0/112 • From screening (Days -28 to -1) until Week 28 (follow-up visit) An AEs is the development of an undesirable medical condition or the deterioration of a preexisting medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product.	0.00% 0/115 • From screening (Days -28 to -1) until Week 28 (follow-up visit) An AEs is the development of an undesirable medical condition or the deterioration of a preexisting medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product.	0.83% 1/120 • From screening (Days -28 to -1) until Week 28 (follow-up visit) An AEs is the development of an undesirable medical condition or the deterioration of a preexisting medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product.
Injury, poisoning and procedural complications Humerus fracture	0.00% 0/112 • From screening (Days -28 to -1) until Week 28 (follow-up visit) An AEs is the development of an undesirable medical condition or the deterioration of a preexisting medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product.	0.00% 0/115 • From screening (Days -28 to -1) until Week 28 (follow-up visit) An AEs is the development of an undesirable medical condition or the deterioration of a preexisting medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product.	0.83% 1/120 • From screening (Days -28 to -1) until Week 28 (follow-up visit) An AEs is the development of an undesirable medical condition or the deterioration of a preexisting medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product.
Injury, poisoning and procedural complications Lower limb fracture	0.89% 1/112 • From screening (Days -28 to -1) until Week 28 (follow-up visit) An AEs is the development of an undesirable medical condition or the deterioration of a preexisting medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product.	0.00% 0/115 • From screening (Days -28 to -1) until Week 28 (follow-up visit) An AEs is the development of an undesirable medical condition or the deterioration of a preexisting medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product.	0.00% 0/120 • From screening (Days -28 to -1) until Week 28 (follow-up visit) An AEs is the development of an undesirable medical condition or the deterioration of a preexisting medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product.
Injury, poisoning and procedural complications Pelvic fracture	0.00% 0/112 • From screening (Days -28 to -1) until Week 28 (follow-up visit) An AEs is the development of an undesirable medical condition or the deterioration of a preexisting medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product.	0.87% 1/115 • From screening (Days -28 to -1) until Week 28 (follow-up visit) An AEs is the development of an undesirable medical condition or the deterioration of a preexisting medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product.	0.00% 0/120 • From screening (Days -28 to -1) until Week 28 (follow-up visit) An AEs is the development of an undesirable medical condition or the deterioration of a preexisting medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product.
Injury, poisoning and procedural complications Spinal compression fracture	0.89% 1/112 • From screening (Days -28 to -1) until Week 28 (follow-up visit) An AEs is the development of an undesirable medical condition or the deterioration of a preexisting medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product.	0.00% 0/115 • From screening (Days -28 to -1) until Week 28 (follow-up visit) An AEs is the development of an undesirable medical condition or the deterioration of a preexisting medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product.	0.00% 0/120 • From screening (Days -28 to -1) until Week 28 (follow-up visit) An AEs is the development of an undesirable medical condition or the deterioration of a preexisting medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product.
Nervous system disorders Cerebrovascular accident	0.00% 0/112 • From screening (Days -28 to -1) until Week 28 (follow-up visit) An AEs is the development of an undesirable medical condition or the deterioration of a preexisting medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product.	1.7% 2/115 • From screening (Days -28 to -1) until Week 28 (follow-up visit) An AEs is the development of an undesirable medical condition or the deterioration of a preexisting medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product.	0.00% 0/120 • From screening (Days -28 to -1) until Week 28 (follow-up visit) An AEs is the development of an undesirable medical condition or the deterioration of a preexisting medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product.
Nervous system disorders Cerebral arteriosclerosis	0.89% 1/112 • From screening (Days -28 to -1) until Week 28 (follow-up visit) An AEs is the development of an undesirable medical condition or the deterioration of a preexisting medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product.	0.00% 0/115 • From screening (Days -28 to -1) until Week 28 (follow-up visit) An AEs is the development of an undesirable medical condition or the deterioration of a preexisting medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product.	0.00% 0/120 • From screening (Days -28 to -1) until Week 28 (follow-up visit) An AEs is the development of an undesirable medical condition or the deterioration of a preexisting medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product.
Nervous system disorders Cerebrovascular insufficiency	0.00% 0/112 • From screening (Days -28 to -1) until Week 28 (follow-up visit) An AEs is the development of an undesirable medical condition or the deterioration of a preexisting medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product.	0.87% 1/115 • From screening (Days -28 to -1) until Week 28 (follow-up visit) An AEs is the development of an undesirable medical condition or the deterioration of a preexisting medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product.	0.00% 0/120 • From screening (Days -28 to -1) until Week 28 (follow-up visit) An AEs is the development of an undesirable medical condition or the deterioration of a preexisting medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product.
Nervous system disorders Dizziness	0.00% 0/112 • From screening (Days -28 to -1) until Week 28 (follow-up visit) An AEs is the development of an undesirable medical condition or the deterioration of a preexisting medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product.	0.00% 0/115 • From screening (Days -28 to -1) until Week 28 (follow-up visit) An AEs is the development of an undesirable medical condition or the deterioration of a preexisting medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product.	0.83% 1/120 • From screening (Days -28 to -1) until Week 28 (follow-up visit) An AEs is the development of an undesirable medical condition or the deterioration of a preexisting medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product.
Nervous system disorders Ischaemic stroke	0.00% 0/112 • From screening (Days -28 to -1) until Week 28 (follow-up visit) An AEs is the development of an undesirable medical condition or the deterioration of a preexisting medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product.	0.00% 0/115 • From screening (Days -28 to -1) until Week 28 (follow-up visit) An AEs is the development of an undesirable medical condition or the deterioration of a preexisting medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product.	0.83% 1/120 • From screening (Days -28 to -1) until Week 28 (follow-up visit) An AEs is the development of an undesirable medical condition or the deterioration of a preexisting medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product.
General disorders Sudden cardiac death	0.00% 0/112 • From screening (Days -28 to -1) until Week 28 (follow-up visit) An AEs is the development of an undesirable medical condition or the deterioration of a preexisting medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product.	0.87% 1/115 • From screening (Days -28 to -1) until Week 28 (follow-up visit) An AEs is the development of an undesirable medical condition or the deterioration of a preexisting medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product.	1.7% 2/120 • From screening (Days -28 to -1) until Week 28 (follow-up visit) An AEs is the development of an undesirable medical condition or the deterioration of a preexisting medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product.
General disorders Cardiac death	0.89% 1/112 • From screening (Days -28 to -1) until Week 28 (follow-up visit) An AEs is the development of an undesirable medical condition or the deterioration of a preexisting medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product.	0.00% 0/115 • From screening (Days -28 to -1) until Week 28 (follow-up visit) An AEs is the development of an undesirable medical condition or the deterioration of a preexisting medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product.	0.00% 0/120 • From screening (Days -28 to -1) until Week 28 (follow-up visit) An AEs is the development of an undesirable medical condition or the deterioration of a preexisting medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product.
General disorders Death	0.00% 0/112 • From screening (Days -28 to -1) until Week 28 (follow-up visit) An AEs is the development of an undesirable medical condition or the deterioration of a preexisting medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product.	0.87% 1/115 • From screening (Days -28 to -1) until Week 28 (follow-up visit) An AEs is the development of an undesirable medical condition or the deterioration of a preexisting medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product.	0.00% 0/120 • From screening (Days -28 to -1) until Week 28 (follow-up visit) An AEs is the development of an undesirable medical condition or the deterioration of a preexisting medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product.
Skin and subcutaneous tissue disorders Diabetic foot	0.89% 1/112 • From screening (Days -28 to -1) until Week 28 (follow-up visit) An AEs is the development of an undesirable medical condition or the deterioration of a preexisting medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product.	0.87% 1/115 • From screening (Days -28 to -1) until Week 28 (follow-up visit) An AEs is the development of an undesirable medical condition or the deterioration of a preexisting medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product.	0.83% 1/120 • From screening (Days -28 to -1) until Week 28 (follow-up visit) An AEs is the development of an undesirable medical condition or the deterioration of a preexisting medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product.
Skin and subcutaneous tissue disorders Skin ulcer	0.89% 1/112 • From screening (Days -28 to -1) until Week 28 (follow-up visit) An AEs is the development of an undesirable medical condition or the deterioration of a preexisting medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product.	0.00% 0/115 • From screening (Days -28 to -1) until Week 28 (follow-up visit) An AEs is the development of an undesirable medical condition or the deterioration of a preexisting medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product.	0.00% 0/120 • From screening (Days -28 to -1) until Week 28 (follow-up visit) An AEs is the development of an undesirable medical condition or the deterioration of a preexisting medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product.
Renal and urinary disorders Acute kidney injury	0.00% 0/112 • From screening (Days -28 to -1) until Week 28 (follow-up visit) An AEs is the development of an undesirable medical condition or the deterioration of a preexisting medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product.	0.00% 0/115 • From screening (Days -28 to -1) until Week 28 (follow-up visit) An AEs is the development of an undesirable medical condition or the deterioration of a preexisting medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product.	0.83% 1/120 • From screening (Days -28 to -1) until Week 28 (follow-up visit) An AEs is the development of an undesirable medical condition or the deterioration of a preexisting medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product.
Renal and urinary disorders Cystitis haemorrhagic	0.00% 0/112 • From screening (Days -28 to -1) until Week 28 (follow-up visit) An AEs is the development of an undesirable medical condition or the deterioration of a preexisting medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product.	0.87% 1/115 • From screening (Days -28 to -1) until Week 28 (follow-up visit) An AEs is the development of an undesirable medical condition or the deterioration of a preexisting medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product.	0.00% 0/120 • From screening (Days -28 to -1) until Week 28 (follow-up visit) An AEs is the development of an undesirable medical condition or the deterioration of a preexisting medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product.
Renal and urinary disorders Renal colic	0.00% 0/112 • From screening (Days -28 to -1) until Week 28 (follow-up visit) An AEs is the development of an undesirable medical condition or the deterioration of a preexisting medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product.	0.87% 1/115 • From screening (Days -28 to -1) until Week 28 (follow-up visit) An AEs is the development of an undesirable medical condition or the deterioration of a preexisting medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product.	0.00% 0/120 • From screening (Days -28 to -1) until Week 28 (follow-up visit) An AEs is the development of an undesirable medical condition or the deterioration of a preexisting medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product.
Hepatobiliary disorders Bile duct stone	0.00% 0/112 • From screening (Days -28 to -1) until Week 28 (follow-up visit) An AEs is the development of an undesirable medical condition or the deterioration of a preexisting medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product.	0.00% 0/115 • From screening (Days -28 to -1) until Week 28 (follow-up visit) An AEs is the development of an undesirable medical condition or the deterioration of a preexisting medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product.	0.83% 1/120 • From screening (Days -28 to -1) until Week 28 (follow-up visit) An AEs is the development of an undesirable medical condition or the deterioration of a preexisting medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product.
Hepatobiliary disorders Cholelithiasis	0.00% 0/112 • From screening (Days -28 to -1) until Week 28 (follow-up visit) An AEs is the development of an undesirable medical condition or the deterioration of a preexisting medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product.	0.87% 1/115 • From screening (Days -28 to -1) until Week 28 (follow-up visit) An AEs is the development of an undesirable medical condition or the deterioration of a preexisting medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product.	0.00% 0/120 • From screening (Days -28 to -1) until Week 28 (follow-up visit) An AEs is the development of an undesirable medical condition or the deterioration of a preexisting medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product.
Metabolism and nutrition disorders Diabetes mellitus inadequate control	0.00% 0/112 • From screening (Days -28 to -1) until Week 28 (follow-up visit) An AEs is the development of an undesirable medical condition or the deterioration of a preexisting medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product.	0.00% 0/115 • From screening (Days -28 to -1) until Week 28 (follow-up visit) An AEs is the development of an undesirable medical condition or the deterioration of a preexisting medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product.	0.83% 1/120 • From screening (Days -28 to -1) until Week 28 (follow-up visit) An AEs is the development of an undesirable medical condition or the deterioration of a preexisting medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product.
Metabolism and nutrition disorders Lactic acidosis	0.00% 0/112 • From screening (Days -28 to -1) until Week 28 (follow-up visit) An AEs is the development of an undesirable medical condition or the deterioration of a preexisting medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product.	0.00% 0/115 • From screening (Days -28 to -1) until Week 28 (follow-up visit) An AEs is the development of an undesirable medical condition or the deterioration of a preexisting medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product.	0.83% 1/120 • From screening (Days -28 to -1) until Week 28 (follow-up visit) An AEs is the development of an undesirable medical condition or the deterioration of a preexisting medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product.
Vascular disorders Hypertensive crisis	0.00% 0/112 • From screening (Days -28 to -1) until Week 28 (follow-up visit) An AEs is the development of an undesirable medical condition or the deterioration of a preexisting medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product.	0.00% 0/115 • From screening (Days -28 to -1) until Week 28 (follow-up visit) An AEs is the development of an undesirable medical condition or the deterioration of a preexisting medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product.	0.83% 1/120 • From screening (Days -28 to -1) until Week 28 (follow-up visit) An AEs is the development of an undesirable medical condition or the deterioration of a preexisting medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product.
Vascular disorders Peripheral arterial occlusive disease	0.00% 0/112 • From screening (Days -28 to -1) until Week 28 (follow-up visit) An AEs is the development of an undesirable medical condition or the deterioration of a preexisting medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product.	0.00% 0/115 • From screening (Days -28 to -1) until Week 28 (follow-up visit) An AEs is the development of an undesirable medical condition or the deterioration of a preexisting medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product.	0.83% 1/120 • From screening (Days -28 to -1) until Week 28 (follow-up visit) An AEs is the development of an undesirable medical condition or the deterioration of a preexisting medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product.
Blood and lymphatic system disorders Anaemia	0.89% 1/112 • From screening (Days -28 to -1) until Week 28 (follow-up visit) An AEs is the development of an undesirable medical condition or the deterioration of a preexisting medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product.	0.00% 0/115 • From screening (Days -28 to -1) until Week 28 (follow-up visit) An AEs is the development of an undesirable medical condition or the deterioration of a preexisting medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product.	0.00% 0/120 • From screening (Days -28 to -1) until Week 28 (follow-up visit) An AEs is the development of an undesirable medical condition or the deterioration of a preexisting medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product.
Gastrointestinal disorders Enterocolitis	0.00% 0/112 • From screening (Days -28 to -1) until Week 28 (follow-up visit) An AEs is the development of an undesirable medical condition or the deterioration of a preexisting medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product.	0.00% 0/115 • From screening (Days -28 to -1) until Week 28 (follow-up visit) An AEs is the development of an undesirable medical condition or the deterioration of a preexisting medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product.	0.83% 1/120 • From screening (Days -28 to -1) until Week 28 (follow-up visit) An AEs is the development of an undesirable medical condition or the deterioration of a preexisting medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product.
Musculoskeletal and connective tissue disorders Back disorder	0.00% 0/112 • From screening (Days -28 to -1) until Week 28 (follow-up visit) An AEs is the development of an undesirable medical condition or the deterioration of a preexisting medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product.	0.87% 1/115 • From screening (Days -28 to -1) until Week 28 (follow-up visit) An AEs is the development of an undesirable medical condition or the deterioration of a preexisting medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product.	0.00% 0/120 • From screening (Days -28 to -1) until Week 28 (follow-up visit) An AEs is the development of an undesirable medical condition or the deterioration of a preexisting medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product.
Psychiatric disorders Depression	0.89% 1/112 • From screening (Days -28 to -1) until Week 28 (follow-up visit) An AEs is the development of an undesirable medical condition or the deterioration of a preexisting medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product.	0.00% 0/115 • From screening (Days -28 to -1) until Week 28 (follow-up visit) An AEs is the development of an undesirable medical condition or the deterioration of a preexisting medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product.	0.00% 0/120 • From screening (Days -28 to -1) until Week 28 (follow-up visit) An AEs is the development of an undesirable medical condition or the deterioration of a preexisting medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product.
Respiratory, thoracic and mediastinal disorders Dyspnoea paroxysmal nocturnal	0.00% 0/112 • From screening (Days -28 to -1) until Week 28 (follow-up visit) An AEs is the development of an undesirable medical condition or the deterioration of a preexisting medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product.	0.00% 0/115 • From screening (Days -28 to -1) until Week 28 (follow-up visit) An AEs is the development of an undesirable medical condition or the deterioration of a preexisting medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product.	0.83% 1/120 • From screening (Days -28 to -1) until Week 28 (follow-up visit) An AEs is the development of an undesirable medical condition or the deterioration of a preexisting medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product.

Other adverse events

Measure	Saxagliptin n=112 participants at risk Participants with an eGFR ≥50 mL/min/1.73m\^2 received one saxagliptin 5 mg tablet and one sitaglipitin placebo capsule administered orally once daily for a 24-week treatment period. Participants with an eGFR ≥30 to \<50 mL/min/1.73m\^2, the dose of saxagliptin was adjusted to one 2.5 mg tablet.	Sitagliptin n=115 participants at risk Participants with an eGFR ≥50 mL/min/1.73m\^2 received one sitagliptin 100 mg capsule and one saxagliptin placebo tablet administered orally once daily for a 24-week treatment period. Participants with an eGFR ≥30 to \<50 mL/min/1.73m\^2, the dose of sitagliptin was adjusted to one 50 mg capsule.	Placebo n=120 participants at risk Participants recieved one saxagliptin placebo tablet and one sitagliptin placebo capsule administered orally once daily for a 24-week treatment period as a control.
Cardiac disorders Cardiac failure	1.8% 2/112 • Number of events 2 • From screening (Days -28 to -1) until Week 28 (follow-up visit) An AEs is the development of an undesirable medical condition or the deterioration of a preexisting medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product.	4.3% 5/115 • Number of events 5 • From screening (Days -28 to -1) until Week 28 (follow-up visit) An AEs is the development of an undesirable medical condition or the deterioration of a preexisting medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product.	3.3% 4/120 • Number of events 4 • From screening (Days -28 to -1) until Week 28 (follow-up visit) An AEs is the development of an undesirable medical condition or the deterioration of a preexisting medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product.
Metabolism and nutrition disorders Hyperglycaemia	4.5% 5/112 • Number of events 5 • From screening (Days -28 to -1) until Week 28 (follow-up visit) An AEs is the development of an undesirable medical condition or the deterioration of a preexisting medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product.	2.6% 3/115 • Number of events 3 • From screening (Days -28 to -1) until Week 28 (follow-up visit) An AEs is the development of an undesirable medical condition or the deterioration of a preexisting medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product.	0.83% 1/120 • Number of events 1 • From screening (Days -28 to -1) until Week 28 (follow-up visit) An AEs is the development of an undesirable medical condition or the deterioration of a preexisting medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product.
Vascular disorders Hypertension	0.89% 1/112 • Number of events 1 • From screening (Days -28 to -1) until Week 28 (follow-up visit) An AEs is the development of an undesirable medical condition or the deterioration of a preexisting medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product.	1.7% 2/115 • Number of events 2 • From screening (Days -28 to -1) until Week 28 (follow-up visit) An AEs is the development of an undesirable medical condition or the deterioration of a preexisting medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product.	3.3% 4/120 • Number of events 4 • From screening (Days -28 to -1) until Week 28 (follow-up visit) An AEs is the development of an undesirable medical condition or the deterioration of a preexisting medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product.

Additional Information

AstraZeneca R&D

AstraZeneca R&D

Phone: +46 766 346712

Email: clinicaltrialtransparency@astrazeneca.com

Results disclosure agreements

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