Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 2 of 2 for:    "Adenoma" | "Zinc"

Study of Management of Pasireotide-induced Hyperglycemia in Adult Patients With Cushing's Disease or Acromegaly

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02060383
Recruitment Status : Completed
First Posted : February 12, 2014
Results First Posted : May 29, 2019
Last Update Posted : May 29, 2019
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Supportive Care
Conditions Cushing's Disease
Acromegaly
Interventions Drug: Pasireotide s.c.
Drug: Sitagliptin
Drug: Liraglutide
Drug: Insulin
Drug: Pasireotide LAR
Drug: Metformin
Enrollment 249
Recruitment Details A total of 68 randomized evaluable participants with at least 8 weeks of randomized treatment without any rescue anti-diabetic medication was required. Approximately 79 participants were planned to be randomized.
Pre-assignment Details 249 participants were included in study & treated with pasireotide s.c. (59 with Cushing's disease) or pasireotide LAR (190 with acromegaly). Following pre-randomization period (up to 16 weeks), 81 participants were randomized to either incretin-based therapy or insulin (72 evaluable for the primary analysis) & 168 not qualified for randomization.
Arm/Group Title Incretin Based Therapy (Randomized Group) Insulin (Randomized Group) Baseline Insulin (BL) (Non-randomized Group) Oral Antidiabetic Drugs (OAD) (Non-randomized Group) No OAD (Non-randomized Group)
Hide Arm/Group Description Participants randomized to the incretin based arm started with sitagliptin once daily. If sitagliptin did not control the participant's hyperglycemia, sitagliptin was stopped and participants switched to liraglutide once daily. If despite treatment with liraglutide, hyperglycemia was not controlled then the participant was eligible for rescue therapy with addition of insulin Participants randomized to the insulin arm started with once daily dose of basal insulin. The dose was up or down titrated at the discretion of the investigator. If blood glucose levels remained uncontrolled on basal insulin, participant switched to basal insulin plus prandial insulin. This group included participants who were receiving insulin at study entry. This group included participants who developed hyperglycemia that was controlled by metformin and/or other background anti-diabetic treatment. Patients in this group did not require additional treatment with either incretin or insulin. This group included participants who did not receive any anti-diabetic medication during the Core Phase of the study as they did not develop hyperglycemia.
Period Title: Core Phase
Started [1] 38 43 19 46 103
Completed Core/Entered Extension 17 17 10 21 53
Completed Core/Did Not Enter Extension 18 20 9 18 42
Completed 35 37 19 39 95
Not Completed 3 6 0 7 8
Reason Not Completed
Unsatisfactory therapeutic effect             1             5             0             0             0
Adverse Event             2             0             0             2             6
Administrative problems             0             1             0             0             0
Protocol Violation             0             0             0             1             0
Withdrawal by Subject             0             0             0             4             2
[1]
Entered Core Phase of Study
Period Title: Extension Phase
Started [1] 17 17 10 21 53
Completed [2] 14 14 7 19 46
Not Completed 3 3 3 2 7
Reason Not Completed
Unsatisfactory therapeutic effect             1             1             0             2             2
Adverse Event             1             1             2             0             1
Withdrawal by Subject             0             1             0             0             2
Administrative problems             1             0             0             0             0
Death             0             0             1             0             1
Protocol Violation             0             0             0             0             1
[1]
Entered the Extension phase from the Core phase
[2]
Completed the Extension phase
Arm/Group Title Incretin Based Therapy (Randomized Group) Insulin (Randomized Group) Baseline Insulin (BL) (Non-randomized Group) Oral Antidiabetic Drugs (OAD) (Non-randomized Group) No OAD (Non-randomized Group) Total
Hide Arm/Group Description Participants randomized to the incretin based arm started with sitagliptin once daily. If sitagliptin did not control the participant's hyperglycemia, sitagliptin was stopped and participants switched to liraglutide once daily. If despite treatment with liraglutide, hyperglycemia was not controlled then the participant was eligible for rescue therapy with addition of insulin Participants randomized to the insulin arm started with once daily dose of basal insulin. The dose was up or down titrated at the discretion of the investigator. If blood glucose levels remained uncontrolled on basal insulin, participant switched to basal insulin plus prandial insulin. This group included participants who were receiving insulin at study entry. This group included participants who developed hyperglycemia that was controlled by metformin and/or other background anti-diabetic treatment. Patients in this group did not require additional treatment with either incretin or insulin. This group included participants who did not receive any anti-diabetic medication during the Core Phase of the study as they did not develop hyperglycemia. Total of all reporting groups
Overall Number of Baseline Participants 38 43 19 46 103 249
Hide Baseline Analysis Population Description
Full Analysis Set (FAS): all participants who received at least one dose of pasireotide.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 38 participants 43 participants 19 participants 46 participants 103 participants 249 participants
50.6  (11.76) 46.4  (12.90) 46.7  (12.54) 40.2  (13.80) 37.8  (11.17) 42.4  (13.05)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 38 participants 43 participants 19 participants 46 participants 103 participants 249 participants
Female
22
  57.9%
27
  62.8%
10
  52.6%
31
  67.4%
47
  45.6%
137
  55.0%
Male
16
  42.1%
16
  37.2%
9
  47.4%
15
  32.6%
56
  54.4%
112
  45.0%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 38 participants 43 participants 19 participants 46 participants 103 participants 249 participants
Other 22 24 11 25 43 125
Chinese 5 9 1 13 33 61
Hispanic/Latino 7 2 5 6 19 39
Indian (Indian subcontinent) 4 8 2 2 7 23
Japanese 0 0 0 0 1 1
1.Primary Outcome
Title Change in HbA1c From Randomization to Approximately 16 Weeks
Hide Description Absolute change in HbA1c from randomization to end of core phase (16 weeks) in incretin based therapy arm and insulin arm, and mean difference of change in HbA1c between the two treatment groups based on an ANOVA model using treatment (Incretin, Insulin) and the two randomization stratification factors (Disease: Cushing’s disease vs Acromegaly; Baseline glycemic status: HbA1c <7% vs HbA1c ≥ 7%) as fixed effects. For Participants who discontinued the study or required rescue treatment before the time of assessing the primary endpoint, the last HbA1c assessment collected 8 weeks (56 days) after randomization (and prior to or on the date of start of rescue treatment) was carried forward. If the participant discontinued the study or used rescue treatment within 8 weeks after randomization, it was considered missing.
Time Frame Randomization, 16 weeks
Hide Outcome Measure Data
Hide Analysis Population Description

Randomized Analysis Set (RAS): all patients who received at least one dose of pasireotide and were assigned to either incretin based therapy or insulin by randomization.

If the patient discontinued the study or used rescue treatment within 8 weeks after randomization, it was considered missing.

Arm/Group Title Incretin Based Therapy (Randomized Group) Insulin (Randomized Group)
Hide Arm/Group Description:
Participants randomized to the incretin based arm started with sitagliptin once daily. If sitagliptin did not control the participant's hyperglycemia, sitagliptin was stopped and participants switched to liraglutide once daily. If despite treatment with liraglutide, hyperglycemia was not controlled then the participant was eligible for rescue therapy with addition of insulin
Participants randomized to the insulin arm started with once daily dose of basal insulin. The dose was up or down titrated at the discretion of the investigator. If blood glucose levels remained uncontrolled on basal insulin, participant switched to basal insulin plus prandial insulin.
Overall Number of Participants Analyzed 31 41
Mean (95% Confidence Interval)
Unit of Measure: Hba1c percentage
All Patients Number Analyzed 31 participants 41 participants
-0.12
(-0.36 to 0.13)
0.26
(-0.01 to 0.53)
Cushing's Disease Number Analyzed 7 participants 11 participants
0.33
(-0.41 to 1.07)
0.45
(-0.20 to 1.09)
Acromegaly Number Analyzed 24 participants 30 participants
-0.25
(-0.49 to -0.00)
0.19
(-0.12 to 0.49)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Incretin Based Therapy (Randomized Group), Insulin (Randomized Group)
Comments All Patients
Type of Statistical Test Other
Comments There was no formal hypothesis testing planned in this study.
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.28
Confidence Interval (2-Sided) 95%
-0.63 to 0.08
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.18
Estimation Comments Difference of adjusted mean change in HbA1c between the two arms based on an ANOVA model with treatment (Incretin, Insulin) and randomization stratification factors (Cushing's vs. Acromegaly; baseline HbA1c <7% vs ≥7%) as fixed effects.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Incretin Based Therapy (Randomized Group), Insulin (Randomized Group)
Comments Cushing's Disease
Type of Statistical Test Other
Comments There was no formal hypothesis testing planned in this study.
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.01
Confidence Interval (2-Sided) 95%
-0.96 to 0.95
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.45
Estimation Comments Difference of adjusted mean change in HbA1c between the two arms based on an ANOVA model with treatment (Incretin, Insulin) and randomization stratification factors (baseline HbA1c <7% vs ≥7%) as fixed effects.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Incretin Based Therapy (Randomized Group), Insulin (Randomized Group)
Comments Acromegaly
Type of Statistical Test Other
Comments There was no formal hypothesis testing planned in this study.
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.36
Confidence Interval (2-Sided) 95%
-0.74 to 0.02
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.19
Estimation Comments Difference of adjusted mean change in HbA1c between the two arms based on an ANOVA model with treatment (Incretin, Insulin) and randomization stratification factors (baseline HbA1c <7% vs ≥7%) as fixed effects.
2.Secondary Outcome
Title Change in HbA1c From Randomization (R) Over Time Per Randomized Arm
Hide Description Absolute change in HbA1c overtime from randomization (i.e. start of randomized antidiabetic treatment) to end of core phase per randomized arm
Time Frame Randomization (R), Week (W) 4 post R, W 8 post R, W 16 post R, end of Core phase (up to week 16 post R)
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized Analysis Set (RAS): all patients who received at least one dose of pasireotide and were assigned to either incretin based therapy or insulin by randomization.
Arm/Group Title Incretin Based Therapy (Randomized Group) Insulin (Randomized Group)
Hide Arm/Group Description:
Participants randomized to the incretin based arm started with sitagliptin once daily. If sitagliptin did not control the participant's hyperglycemia, sitagliptin was stopped and participants switched to liraglutide once daily. If despite treatment with liraglutide, hyperglycemia was not controlled then the participant was eligible for rescue therapy with addition of insulin
Participants randomized to the insulin arm started with once daily dose of basal insulin. The dose was up or down titrated at the discretion of the investigator. If blood glucose levels remained uncontrolled on basal insulin, participant switched to basal insulin plus prandial insulin.
Overall Number of Participants Analyzed 38 43
Mean (Standard Deviation)
Unit of Measure: HbA1c percentage
Randomization Number Analyzed 38 participants 43 participants
7.1  (1.00) 7.1  (0.75)
Change at RW4 D29 Number Analyzed 37 participants 43 participants
0.5  (0.73) 0.5  (0.60)
Change at RW8 D57 Number Analyzed 37 participants 43 participants
0.3  (0.98) 0.5  (0.86)
Change at RW12 D85 Number Analyzed 37 participants 40 participants
0.2  (1.03) 0.4  (0.85)
Change at RW16 D113 Number Analyzed 35 participants 37 participants
0.0  (0.93) 0.3  (0.87)
End of Core Phase Number Analyzed 37 participants 42 participants
0.0  (0.92) 0.3  (0.84)
3.Secondary Outcome
Title Change in FPG (Fasting Plasma Glucose) From Randomization Until End of Core Phase
Hide Description Absolute change in fasting glucose overtime from randomization (i.e. start of randomized antidiabetic treatment) to end of core phase per randomized arm
Time Frame Randomization, R(randomization) Week 2, R-Week 4, R-Week 6, R-Week 8, R-Week 10, R-Week 12, R-Week 14, R-Week 16, end of Core phase
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized Analysis Set (RAS): all patients who received at least one dose of pasireotide and were assigned to either incretin based therapy or insulin by randomization.
Arm/Group Title Incretin Based Therapy (Randomized Group) Insulin (Randomized Group)
Hide Arm/Group Description:
Participants randomized to the incretin based arm started with sitagliptin once daily. If sitagliptin did not control the participant's hyperglycemia, sitagliptin was stopped and participants switched to liraglutide once daily. If despite treatment with liraglutide, hyperglycemia was not controlled then the participant was eligible for rescue therapy with addition of insulin
Participants randomized to the insulin arm started with once daily dose of basal insulin. The dose was up or down titrated at the discretion of the investigator. If blood glucose levels remained uncontrolled on basal insulin, participant switched to basal insulin plus prandial insulin.
Overall Number of Participants Analyzed 38 43
Mean (Standard Deviation)
Unit of Measure: mg/dL
Randomization Number Analyzed 38 participants 43 participants
172.2  (60.78) 167.9  (40.77)
Change at RW2 D15 Number Analyzed 36 participants 42 participants
4.6  (51.01) -31.1  (41.19)
Change at RW4 D29 Number Analyzed 38 participants 43 participants
-15.0  (47.95) -28.3  (41.14)
Change at RW6 D43 Number Analyzed 36 participants 41 participants
-17.7  (57.97) -37.5  (52.39)
Change at RW8 D57 Number Analyzed 36 participants 42 participants
-25.7  (53.32) -38.3  (44.10)
Change at RW10 D71 Number Analyzed 37 participants 37 participants
-28.8  (61.14) -36.9  (50.82)
Change at RW12 D85 Number Analyzed 37 participants 40 participants
-33.4  (50.17) -41.1  (51.68)
Change at RW14 D99 Number Analyzed 36 participants 36 participants
-35.1  (55.83) -35.6  (47.43)
Change at RW16 D113 Number Analyzed 35 participants 34 participants
-38.8  (53.69) -33.4  (47.63)
End of Core Phase Number Analyzed 37 participants 41 participants
-40.1  (56.35) -36.0  (46.90)
4.Secondary Outcome
Title Percentage of Participants in the Incretin-based Arm Who Required Anti-diabetic Rescue Therapy With Insulin
Hide Description The percentage of participants who received anti-diabetic rescue therapy in incretin based therapy is summarized.
Time Frame Randomization to up to 16 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Safety set - All participants randomized to the incretin-based therapy who received at least one dose of pasireotide and had at least one post-baseline safety assessment. Randomized participants within the safety set were analyzed according to the anti-diabetic study treatment first received.
Arm/Group Title Incretin Based Therapy (Randomized Group)
Hide Arm/Group Description:
Participants randomized to the incretin based arm started with sitagliptin once daily. If sitagliptin did not control the participant's hyperglycemia, sitagliptin was stopped and participants switched to liraglutide once daily. If despite treatment with liraglutide, hyperglycemia was not controlled then the participant was eligible for rescue therapy with addition of insulin
Overall Number of Participants Analyzed 38
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
31.6
(17.5 to 48.7)
5.Secondary Outcome
Title Absolute Change in HbA1c From Baseline to End of Core Phase
Hide Description Absolute change in HbA1c from baseline to end of core phase in the incretin based therapy arm and the insulin arm
Time Frame Baseline, up to 32 weeks (end of Core phase)
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set (FAS): Participants who received at least 1 dose of pasireotide. Randomized participants were analyzed according to the anti-diabetic treatment assigned to at randomization. Non-randomized participants were analyzed by the anti-diabetic treatment received during the core phase (insulin at baseline, oral antidiabetics (OAD), none).
Arm/Group Title Incretin Based Therapy (Randomized Group) Insulin (Randomized Group) Baseline Insulin (BL) (Non-randomized Group) Oral Antidiabetic Drugs (OAD) (Non-randomized Group) No OAD (Non-randomized Group)
Hide Arm/Group Description:
Participants randomized to the incretin based arm started with sitagliptin once daily. If sitagliptin did not control the participant's hyperglycemia, sitagliptin was stopped and participants switched to liraglutide once daily. If despite treatment with liraglutide, hyperglycemia was not controlled then the participant was eligible for rescue therapy with addition of insulin
Participants randomized to the insulin arm started with once daily dose of basal insulin. The dose was up or down titrated at the discretion of the investigator. If blood glucose levels remained uncontrolled on basal insulin, participant switched to basal insulin plus prandial insulin.
This group included participants who were receiving insulin at study entry.
This group included participants who developed hyperglycemia that was controlled by metformin and/or other background anti-diabetic treatment. Patients in this group did not require additional treatment with either incretin or insulin.
This group included participants who did not receive any anti-diabetic medication during the Core Phase of the study as they did not develop hyperglycemia.
Overall Number of Participants Analyzed 38 43 19 46 103
Mean (Standard Deviation)
Unit of Measure: HbA1c percentage
Baseline: All Patients Number Analyzed 38 participants 43 participants 19 participants 46 participants 102 participants
6.3  (0.80) 6.3  (0.63) 7.7  (1.51) 5.7  (0.41) 5.4  (0.33)
Change at EOP: All Patients Number Analyzed 37 participants 42 participants 19 participants 45 participants 100 participants
0.8  (0.97) 1.1  (0.94) 1.3  (1.40) 0.8  (0.64) 0.4  (0.32)
Baseline: Cushing's Number Analyzed 12 participants 13 participants 6 participants 13 participants 15 participants
6.6  (0.87) 6.5  (0.58) 6.9  (0.92) 5.9  (0.49) 5.5  (0.41)
Change at EOP: Cushing's Number Analyzed 12 participants 13 participants 6 participants 13 participants 14 participants
1.3  (1.19) 1.7  (1.05) 1.4  (1.58) 0.9  (0.95) 0.5  (0.51)
Baseline: Acromegaly Number Analyzed 26 participants 30 participants 13 participants 33 participants 87 participants
6.1  (0.71) 6.3  (0.65) 8.0  (1.61) 5.6  (0.36) 5.4  (0.32)
Change at EOP: Acromegaly Number Analyzed 25 participants 29 participants 13 participants 32 participants 86 participants
0.6  (0.78) 0.8  (0.78) 1.2  (1.37) 0.7  (0.47) 0.4  (0.28)
6.Secondary Outcome
Title Absolute Change in FPG From Baseline to End of Core Phase
Hide Description Absolute change in FPG from baseline to end of core phase in the incretin based therapy arm and the insulin arm.
Time Frame Baseline, Up to 32 weeks (end of Core Phase)
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set (FAS): All participants who received at least one dose of pasireotide. Randomized patients were analyzed according to the anti-diabetic treatment assigned to at randomization. Non-randomized patients were analyzed by the anti-diabetic treatment received during the core phase (insulin at baseline, oral antidiabetics (OAD), none).
Arm/Group Title Incretin Based Therapy (Randomized Group) Insulin (Randomized Group) Baseline Insulin (BL) (Non-randomized Group) Oral Antidiabetic Drugs (OAD) (Non-randomized Group) No OAD (Non-randomized Group)
Hide Arm/Group Description:
Participants randomized to the incretin based arm started with sitagliptin once daily. If sitagliptin did not control the participant's hyperglycemia, sitagliptin was stopped and participants switched to liraglutide once daily. If despite treatment with liraglutide, hyperglycemia was not controlled then the participant was eligible for rescue therapy with addition of insulin
Participants randomized to the insulin arm started with once daily dose of basal insulin. The dose was up or down titrated at the discretion of the investigator. If blood glucose levels remained uncontrolled on basal insulin, participant switched to basal insulin plus prandial insulin.
This group included participants who were receiving insulin at study entry.
This group included participants who developed hyperglycemia that was controlled by metformin and/or other background anti-diabetic treatment. Patients in this group did not require additional treatment with either incretin or insulin.
This group included participants who did not receive any anti-diabetic medication during the Core Phase of the study as they did not develop hyperglycemia.
Overall Number of Participants Analyzed 38 43 19 46 103
Mean (Standard Deviation)
Unit of Measure: mg/dL
Baseline: All Patients Number Analyzed 38 participants 43 participants 19 participants 46 participants 103 participants
111.1  (18.95) 111.8  (18.20) 157.7  (66.50) 97.2  (14.24) 92.2  (8.58)
Change at EOP: All Patients Number Analyzed 37 participants 41 participants 19 participants 45 participants 101 participants
22.2  (31.67) 22.5  (34.05) 9.8  (75.67) 22.9  (23.40) 16.3  (13.63)
Baseline: Cushing's Number Analyzed 12 participants 13 participants 6 participants 13 participants 15 participants
117.9  (20.99) 106.3  (15.71) 147.2  (68.38) 93.3  (10.98) 85.5  (6.92)
Change at EOP: Cushing's Number Analyzed 12 participants 12 participants 6 participants 13 participants 14 participants
13.4  (34.92) 36.4  (33.11) 21.3  (72.01) 15.8  (18.43) 11.7  (22.11)
Baseline: Acromegaly Number Analyzed 26 participants 30 participants 13 participants 33 participants 88 participants
107.9  (17.46) 114.2  (18.91) 162.5  (67.85) 98.8  (15.20) 93.4  (8.32)
Change at EOP: Acromegaly Number Analyzed 25 participants 29 participants 13 participants 32 participants 87 participants
26.5  (29.79) 16.7  (33.29) 4.6  (79.57) 25.8  (24.82) 17.0  (11.75)
7.Secondary Outcome
Title Percentage of Participants With ≤ 0.3% HbA1c Increase to End of Core Phase
Hide Description Percentage of participants with ≤ 0.3% HbA1c increase in the incretin based therapy arm and the insulin arm.
Time Frame Randomization, up to 16 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized Analysis Set (RAS): all participants who received at least one dose of pasireotide and were assigned to either incretin based therapy or insulin by randomization.
Arm/Group Title Incretin Based Therapy (Randomized Group) Insulin (Randomized Group)
Hide Arm/Group Description:
Participants randomized to the incretin based arm started with sitagliptin once daily. If sitagliptin did not control the participant's hyperglycemia, sitagliptin was stopped and participants switched to liraglutide once daily. If despite treatment with liraglutide, hyperglycemia was not controlled then the participant was eligible for rescue therapy with addition of insulin
Participants randomized to the insulin arm started with once daily dose of basal insulin. The dose was up or down titrated at the discretion of the investigator. If blood glucose levels remained uncontrolled on basal insulin, participant switched to basal insulin plus prandial insulin.
Overall Number of Participants Analyzed 38 43
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
73.7
(56.9 to 86.6)
65.1
(49.1 to 79.0)
Time Frame Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse Events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 46 months.
Adverse Event Reporting Description There are different safety follow-up period for Cushing's and for acromegaly patients: On-treatment period: from day of first dose of study medication to 28 days after last dose of pasireotide s.c. and 84 days after last dose of pasireotide long acting, or the follow-up visit, whichever comes later.
 
Arm/Group Title Incretin Based Therapy (Randomized Group) Insulin (Randomized Group) Baseline Insulin (BL) (Non-randomized Group) Oral Antidiabetic Drugs (OAD) (Non-randomized Group) No OAD (Non-randomized Group)
Hide Arm/Group Description Participants randomized to the incretin based arm started with sitagliptin once daily. If sitagliptin did not control the participant's hyperglycemia, sitagliptin was stopped and participants switched to liraglutide once daily. If despite treatment with liraglutide, hyperglycemia was not controlled then the participant was eligible for rescue therapy with addition of insulin Participants randomized to the insulin arm started with once daily dose of basal insulin. The dose was up or down titrated at the discretion of the investigator. If blood glucose levels remained uncontrolled on basal insulin, participant switched to basal insulin plus prandial insulin. This group included participants who were receiving insulin at study entry. This group included participants who developed hyperglycemia that was controlled by metformin and/or other background anti-diabetic treatment. Patients in this group did not require additional treatment with either incretin or insulin. This group included participants who did not receive any anti-diabetic medication during the Core Phase of the study as they did not develop hyperglycemia.
All-Cause Mortality
Incretin Based Therapy (Randomized Group) Insulin (Randomized Group) Baseline Insulin (BL) (Non-randomized Group) Oral Antidiabetic Drugs (OAD) (Non-randomized Group) No OAD (Non-randomized Group)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/38 (0.00%)   0/43 (0.00%)   1/19 (5.26%)   0/46 (0.00%)   1/103 (0.97%) 
Show Serious Adverse Events Hide Serious Adverse Events
Incretin Based Therapy (Randomized Group) Insulin (Randomized Group) Baseline Insulin (BL) (Non-randomized Group) Oral Antidiabetic Drugs (OAD) (Non-randomized Group) No OAD (Non-randomized Group)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   6/38 (15.79%)   3/43 (6.98%)   4/19 (21.05%)   2/46 (4.35%)   7/103 (6.80%) 
Blood and lymphatic system disorders           
Febrile neutropenia  1  0/38 (0.00%)  0/43 (0.00%)  1/19 (5.26%)  0/46 (0.00%)  0/103 (0.00%) 
Cardiac disorders           
Coronary artery stenosis  1  0/38 (0.00%)  1/43 (2.33%)  0/19 (0.00%)  0/46 (0.00%)  0/103 (0.00%) 
Endocrine disorders           
Cushing's syndrome  1  0/38 (0.00%)  0/43 (0.00%)  0/19 (0.00%)  1/46 (2.17%)  0/103 (0.00%) 
Gastrointestinal disorders           
Diarrhoea  1  1/38 (2.63%)  1/43 (2.33%)  0/19 (0.00%)  0/46 (0.00%)  0/103 (0.00%) 
Pancreatitis acute  1  0/38 (0.00%)  1/43 (2.33%)  0/19 (0.00%)  0/46 (0.00%)  0/103 (0.00%) 
Vomiting  1  1/38 (2.63%)  0/43 (0.00%)  0/19 (0.00%)  0/46 (0.00%)  0/103 (0.00%) 
General disorders           
Fatigue  1  0/38 (0.00%)  1/43 (2.33%)  0/19 (0.00%)  0/46 (0.00%)  0/103 (0.00%) 
Hepatobiliary disorders           
Cholecystitis acute  1  1/38 (2.63%)  0/43 (0.00%)  0/19 (0.00%)  0/46 (0.00%)  0/103 (0.00%) 
Infections and infestations           
Breast abscess  1  0/38 (0.00%)  1/43 (2.33%)  0/19 (0.00%)  0/46 (0.00%)  0/103 (0.00%) 
Cellulitis  1  0/38 (0.00%)  0/43 (0.00%)  1/19 (5.26%)  0/46 (0.00%)  0/103 (0.00%) 
Epiglottitis  1  0/38 (0.00%)  0/43 (0.00%)  0/19 (0.00%)  0/46 (0.00%)  1/103 (0.97%) 
Infectious pleural effusion  1  1/38 (2.63%)  0/43 (0.00%)  0/19 (0.00%)  0/46 (0.00%)  0/103 (0.00%) 
Paronychia  1  0/38 (0.00%)  0/43 (0.00%)  0/19 (0.00%)  1/46 (2.17%)  0/103 (0.00%) 
Sepsis  1  2/38 (5.26%)  0/43 (0.00%)  0/19 (0.00%)  0/46 (0.00%)  0/103 (0.00%) 
Upper respiratory tract infection  1  1/38 (2.63%)  0/43 (0.00%)  0/19 (0.00%)  0/46 (0.00%)  0/103 (0.00%) 
Urinary tract infection  1  1/38 (2.63%)  0/43 (0.00%)  0/19 (0.00%)  0/46 (0.00%)  0/103 (0.00%) 
Injury, poisoning and procedural complications           
Subdural haematoma  1  0/38 (0.00%)  0/43 (0.00%)  0/19 (0.00%)  0/46 (0.00%)  1/103 (0.97%) 
Wound  1  0/38 (0.00%)  0/43 (0.00%)  0/19 (0.00%)  0/46 (0.00%)  1/103 (0.97%) 
Investigations           
Glycosylated haemoglobin increased  1  0/38 (0.00%)  0/43 (0.00%)  1/19 (5.26%)  0/46 (0.00%)  0/103 (0.00%) 
Metabolism and nutrition disorders           
Dehydration  1  1/38 (2.63%)  0/43 (0.00%)  0/19 (0.00%)  0/46 (0.00%)  0/103 (0.00%) 
Diabetes mellitus inadequate control  1  0/38 (0.00%)  0/43 (0.00%)  1/19 (5.26%)  0/46 (0.00%)  0/103 (0.00%) 
Hyperglycaemia  1  1/38 (2.63%)  1/43 (2.33%)  1/19 (5.26%)  0/46 (0.00%)  0/103 (0.00%) 
Hypoglycaemia  1  1/38 (2.63%)  0/43 (0.00%)  0/19 (0.00%)  0/46 (0.00%)  0/103 (0.00%) 
Hypovolaemia  1  1/38 (2.63%)  0/43 (0.00%)  0/19 (0.00%)  0/46 (0.00%)  0/103 (0.00%) 
Lactic acidosis  1  1/38 (2.63%)  0/43 (0.00%)  0/19 (0.00%)  0/46 (0.00%)  0/103 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)           
Papillary thyroid cancer  1  0/38 (0.00%)  0/43 (0.00%)  0/19 (0.00%)  0/46 (0.00%)  1/103 (0.97%) 
Pituitary tumour benign  1  0/38 (0.00%)  0/43 (0.00%)  0/19 (0.00%)  0/46 (0.00%)  1/103 (0.97%) 
Tubular breast carcinoma  1  1/38 (2.63%)  0/43 (0.00%)  0/19 (0.00%)  0/46 (0.00%)  0/103 (0.00%) 
Nervous system disorders           
Seizure  1  1/38 (2.63%)  0/43 (0.00%)  0/19 (0.00%)  0/46 (0.00%)  0/103 (0.00%) 
Pregnancy, puerperium and perinatal conditions           
Abortion spontaneous  1  0/38 (0.00%)  0/43 (0.00%)  0/19 (0.00%)  0/46 (0.00%)  2/103 (1.94%) 
Pregnancy  1  0/38 (0.00%)  0/43 (0.00%)  0/19 (0.00%)  0/46 (0.00%)  1/103 (0.97%) 
Psychiatric disorders           
Mental status changes  1  1/38 (2.63%)  0/43 (0.00%)  0/19 (0.00%)  0/46 (0.00%)  0/103 (0.00%) 
Renal and urinary disorders           
Acute kidney injury  1  1/38 (2.63%)  0/43 (0.00%)  0/19 (0.00%)  0/46 (0.00%)  0/103 (0.00%) 
Renal injury  1  0/38 (0.00%)  0/43 (0.00%)  0/19 (0.00%)  0/46 (0.00%)  1/103 (0.97%) 
Vascular disorders           
Shock  1  1/38 (2.63%)  0/43 (0.00%)  0/19 (0.00%)  0/46 (0.00%)  0/103 (0.00%) 
1
Term from vocabulary, MedDRA (21.0)
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Incretin Based Therapy (Randomized Group) Insulin (Randomized Group) Baseline Insulin (BL) (Non-randomized Group) Oral Antidiabetic Drugs (OAD) (Non-randomized Group) No OAD (Non-randomized Group)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   37/38 (97.37%)   40/43 (93.02%)   18/19 (94.74%)   38/46 (82.61%)   87/103 (84.47%) 
Blood and lymphatic system disorders           
Anaemia  1  0/38 (0.00%)  2/43 (4.65%)  1/19 (5.26%)  2/46 (4.35%)  3/103 (2.91%) 
Leukopenia  1  0/38 (0.00%)  0/43 (0.00%)  1/19 (5.26%)  1/46 (2.17%)  3/103 (2.91%) 
Neutropenia  1  0/38 (0.00%)  0/43 (0.00%)  2/19 (10.53%)  0/46 (0.00%)  1/103 (0.97%) 
Cardiac disorders           
Bradycardia  1  0/38 (0.00%)  0/43 (0.00%)  1/19 (5.26%)  0/46 (0.00%)  1/103 (0.97%) 
Sinus bradycardia  1  0/38 (0.00%)  0/43 (0.00%)  0/19 (0.00%)  1/46 (2.17%)  6/103 (5.83%) 
Ear and labyrinth disorders           
Vertigo  1  0/38 (0.00%)  0/43 (0.00%)  1/19 (5.26%)  0/46 (0.00%)  0/103 (0.00%) 
Endocrine disorders           
Adrenal insufficiency  1  2/38 (5.26%)  0/43 (0.00%)  0/19 (0.00%)  1/46 (2.17%)  1/103 (0.97%) 
Hypothyroidism  1  0/38 (0.00%)  1/43 (2.33%)  0/19 (0.00%)  3/46 (6.52%)  1/103 (0.97%) 
Gastrointestinal disorders           
Abdominal discomfort  1  2/38 (5.26%)  2/43 (4.65%)  0/19 (0.00%)  0/46 (0.00%)  0/103 (0.00%) 
Abdominal distension  1  4/38 (10.53%)  0/43 (0.00%)  0/19 (0.00%)  1/46 (2.17%)  4/103 (3.88%) 
Abdominal pain  1  2/38 (5.26%)  1/43 (2.33%)  0/19 (0.00%)  2/46 (4.35%)  1/103 (0.97%) 
Abdominal pain upper  1  1/38 (2.63%)  2/43 (4.65%)  1/19 (5.26%)  1/46 (2.17%)  2/103 (1.94%) 
Constipation  1  3/38 (7.89%)  0/43 (0.00%)  0/19 (0.00%)  0/46 (0.00%)  3/103 (2.91%) 
Diarrhoea  1  11/38 (28.95%)  12/43 (27.91%)  2/19 (10.53%)  10/46 (21.74%)  21/103 (20.39%) 
Erosive duodenitis  1  0/38 (0.00%)  0/43 (0.00%)  1/19 (5.26%)  0/46 (0.00%)  0/103 (0.00%) 
Gingival hypertrophy  1  0/38 (0.00%)  0/43 (0.00%)  1/19 (5.26%)  0/46 (0.00%)  0/103 (0.00%) 
Nausea  1  13/38 (34.21%)  7/43 (16.28%)  0/19 (0.00%)  5/46 (10.87%)  11/103 (10.68%) 
Vomiting  1  5/38 (13.16%)  0/43 (0.00%)  0/19 (0.00%)  2/46 (4.35%)  1/103 (0.97%) 
General disorders           
Asthenia  1  2/38 (5.26%)  0/43 (0.00%)  0/19 (0.00%)  1/46 (2.17%)  2/103 (1.94%) 
Fatigue  1  4/38 (10.53%)  4/43 (9.30%)  0/19 (0.00%)  1/46 (2.17%)  5/103 (4.85%) 
Peripheral swelling  1  0/38 (0.00%)  0/43 (0.00%)  1/19 (5.26%)  0/46 (0.00%)  0/103 (0.00%) 
Pyrexia  1  1/38 (2.63%)  0/43 (0.00%)  1/19 (5.26%)  1/46 (2.17%)  1/103 (0.97%) 
Hepatobiliary disorders           
Cholelithiasis  1  5/38 (13.16%)  8/43 (18.60%)  0/19 (0.00%)  4/46 (8.70%)  9/103 (8.74%) 
Hepatic steatosis  1  0/38 (0.00%)  1/43 (2.33%)  1/19 (5.26%)  3/46 (6.52%)  1/103 (0.97%) 
Infections and infestations           
Bone abscess  1  0/38 (0.00%)  0/43 (0.00%)  1/19 (5.26%)  0/46 (0.00%)  0/103 (0.00%) 
Nasopharyngitis  1  3/38 (7.89%)  4/43 (9.30%)  0/19 (0.00%)  3/46 (6.52%)  16/103 (15.53%) 
Onychomycosis  1  0/38 (0.00%)  1/43 (2.33%)  1/19 (5.26%)  0/46 (0.00%)  0/103 (0.00%) 
Pharyngitis  1  0/38 (0.00%)  0/43 (0.00%)  1/19 (5.26%)  0/46 (0.00%)  4/103 (3.88%) 
Pneumonia  1  0/38 (0.00%)  0/43 (0.00%)  1/19 (5.26%)  0/46 (0.00%)  0/103 (0.00%) 
Respiratory tract infection viral  1  2/38 (5.26%)  0/43 (0.00%)  0/19 (0.00%)  0/46 (0.00%)  0/103 (0.00%) 
Subcutaneous abscess  1  0/38 (0.00%)  0/43 (0.00%)  1/19 (5.26%)  0/46 (0.00%)  1/103 (0.97%) 
Upper respiratory tract infection  1  2/38 (5.26%)  3/43 (6.98%)  3/19 (15.79%)  6/46 (13.04%)  15/103 (14.56%) 
Urinary tract infection  1  3/38 (7.89%)  5/43 (11.63%)  1/19 (5.26%)  0/46 (0.00%)  4/103 (3.88%) 
Injury, poisoning and procedural complications           
Laceration  1  0/38 (0.00%)  0/43 (0.00%)  1/19 (5.26%)  0/46 (0.00%)  0/103 (0.00%) 
Investigations           
Alanine aminotransferase increased  1  3/38 (7.89%)  2/43 (4.65%)  1/19 (5.26%)  1/46 (2.17%)  2/103 (1.94%) 
Aspartate aminotransferase increased  1  2/38 (5.26%)  3/43 (6.98%)  1/19 (5.26%)  1/46 (2.17%)  2/103 (1.94%) 
Bacterial test positive  1  0/38 (0.00%)  0/43 (0.00%)  1/19 (5.26%)  0/46 (0.00%)  0/103 (0.00%) 
Blood creatine phosphokinase increased  1  2/38 (5.26%)  0/43 (0.00%)  1/19 (5.26%)  1/46 (2.17%)  5/103 (4.85%) 
Blood creatinine increased  1  2/38 (5.26%)  0/43 (0.00%)  0/19 (0.00%)  0/46 (0.00%)  0/103 (0.00%) 
Blood glucose increased  1  2/38 (5.26%)  1/43 (2.33%)  0/19 (0.00%)  3/46 (6.52%)  9/103 (8.74%) 
Blood insulin increased  1  1/38 (2.63%)  0/43 (0.00%)  1/19 (5.26%)  0/46 (0.00%)  1/103 (0.97%) 
Blood urea increased  1  1/38 (2.63%)  0/43 (0.00%)  1/19 (5.26%)  0/46 (0.00%)  0/103 (0.00%) 
Blood uric acid increased  1  0/38 (0.00%)  2/43 (4.65%)  1/19 (5.26%)  0/46 (0.00%)  0/103 (0.00%) 
Carbon dioxide decreased  1  0/38 (0.00%)  0/43 (0.00%)  1/19 (5.26%)  0/46 (0.00%)  0/103 (0.00%) 
Gamma-glutamyltransferase increased  1  2/38 (5.26%)  4/43 (9.30%)  0/19 (0.00%)  2/46 (4.35%)  0/103 (0.00%) 
Glycosylated haemoglobin increased  1  3/38 (7.89%)  1/43 (2.33%)  0/19 (0.00%)  0/46 (0.00%)  1/103 (0.97%) 
Lipase increased  1  3/38 (7.89%)  2/43 (4.65%)  0/19 (0.00%)  1/46 (2.17%)  5/103 (4.85%) 
Weight decreased  1  10/38 (26.32%)  4/43 (9.30%)  0/19 (0.00%)  5/46 (10.87%)  2/103 (1.94%) 
Weight increased  1  0/38 (0.00%)  1/43 (2.33%)  1/19 (5.26%)  2/46 (4.35%)  0/103 (0.00%) 
Metabolism and nutrition disorders           
Decreased appetite  1  3/38 (7.89%)  3/43 (6.98%)  0/19 (0.00%)  1/46 (2.17%)  2/103 (1.94%) 
Diabetes mellitus  1  5/38 (13.16%)  9/43 (20.93%)  2/19 (10.53%)  14/46 (30.43%)  4/103 (3.88%) 
Dyslipidaemia  1  0/38 (0.00%)  1/43 (2.33%)  1/19 (5.26%)  3/46 (6.52%)  2/103 (1.94%) 
Hyperglycaemia  1  14/38 (36.84%)  11/43 (25.58%)  6/19 (31.58%)  9/46 (19.57%)  13/103 (12.62%) 
Hypertriglyceridaemia  1  3/38 (7.89%)  1/43 (2.33%)  0/19 (0.00%)  0/46 (0.00%)  1/103 (0.97%) 
Hypoglycaemia  1  5/38 (13.16%)  10/43 (23.26%)  8/19 (42.11%)  5/46 (10.87%)  4/103 (3.88%) 
Hypokalaemia  1  3/38 (7.89%)  0/43 (0.00%)  1/19 (5.26%)  2/46 (4.35%)  0/103 (0.00%) 
Impaired fasting glucose  1  0/38 (0.00%)  2/43 (4.65%)  0/19 (0.00%)  2/46 (4.35%)  14/103 (13.59%) 
Type 2 diabetes mellitus  1  2/38 (5.26%)  1/43 (2.33%)  0/19 (0.00%)  1/46 (2.17%)  1/103 (0.97%) 
Musculoskeletal and connective tissue disorders           
Arthralgia  1  0/38 (0.00%)  0/43 (0.00%)  0/19 (0.00%)  1/46 (2.17%)  8/103 (7.77%) 
Back pain  1  0/38 (0.00%)  3/43 (6.98%)  0/19 (0.00%)  2/46 (4.35%)  5/103 (4.85%) 
Muscular weakness  1  3/38 (7.89%)  2/43 (4.65%)  0/19 (0.00%)  0/46 (0.00%)  0/103 (0.00%) 
Myalgia  1  1/38 (2.63%)  2/43 (4.65%)  1/19 (5.26%)  4/46 (8.70%)  1/103 (0.97%) 
Osteopenia  1  0/38 (0.00%)  0/43 (0.00%)  1/19 (5.26%)  0/46 (0.00%)  0/103 (0.00%) 
Nervous system disorders           
Dizziness  1  5/38 (13.16%)  5/43 (11.63%)  0/19 (0.00%)  3/46 (6.52%)  6/103 (5.83%) 
Dysgeusia  1  2/38 (5.26%)  0/43 (0.00%)  0/19 (0.00%)  0/46 (0.00%)  0/103 (0.00%) 
Headache  1  4/38 (10.53%)  4/43 (9.30%)  0/19 (0.00%)  2/46 (4.35%)  12/103 (11.65%) 
Syncope  1  0/38 (0.00%)  0/43 (0.00%)  1/19 (5.26%)  0/46 (0.00%)  0/103 (0.00%) 
Renal and urinary disorders           
Glycosuria  1  0/38 (0.00%)  1/43 (2.33%)  1/19 (5.26%)  0/46 (0.00%)  0/103 (0.00%) 
Haematuria  1  3/38 (7.89%)  0/43 (0.00%)  0/19 (0.00%)  0/46 (0.00%)  1/103 (0.97%) 
Nephrolithiasis  1  0/38 (0.00%)  1/43 (2.33%)  1/19 (5.26%)  0/46 (0.00%)  0/103 (0.00%) 
Reproductive system and breast disorders           
Amenorrhoea  1  0/38 (0.00%)  1/43 (2.33%)  1/19 (5.26%)  0/46 (0.00%)  0/103 (0.00%) 
Polycystic ovaries  1  0/38 (0.00%)  0/43 (0.00%)  1/19 (5.26%)  0/46 (0.00%)  0/103 (0.00%) 
Respiratory, thoracic and mediastinal disorders           
Rhinitis allergic  1  0/38 (0.00%)  0/43 (0.00%)  1/19 (5.26%)  0/46 (0.00%)  1/103 (0.97%) 
Skin and subcutaneous tissue disorders           
Alopecia  1  2/38 (5.26%)  1/43 (2.33%)  0/19 (0.00%)  0/46 (0.00%)  3/103 (2.91%) 
Pruritus generalised  1  2/38 (5.26%)  1/43 (2.33%)  0/19 (0.00%)  0/46 (0.00%)  0/103 (0.00%) 
Rash  1  3/38 (7.89%)  2/43 (4.65%)  1/19 (5.26%)  1/46 (2.17%)  2/103 (1.94%) 
Rash generalised  1  0/38 (0.00%)  0/43 (0.00%)  1/19 (5.26%)  0/46 (0.00%)  0/103 (0.00%) 
Skin ulcer  1  0/38 (0.00%)  0/43 (0.00%)  1/19 (5.26%)  0/46 (0.00%)  0/103 (0.00%) 
Vascular disorders           
Hypotension  1  2/38 (5.26%)  0/43 (0.00%)  1/19 (5.26%)  0/46 (0.00%)  0/103 (0.00%) 
1
Term from vocabulary, MedDRA (21.0)
Indicates events were collected by systematic assessment
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 terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of pooled data (i.e.,data from all sites) in clinical trial or disclosure of trial results in their entirety.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Study Director
Organization: Novartis Pharmaceuticals
Phone: 862-778-8300
EMail: novartis.email@novartis.com
Layout table for additonal information
Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT02060383     History of Changes
Other Study ID Numbers: CSOM230B2219
2012-002916-16 ( EudraCT Number )
First Submitted: February 10, 2014
First Posted: February 12, 2014
Results First Submitted: February 28, 2019
Results First Posted: May 29, 2019
Last Update Posted: May 29, 2019