Acromegaly, Cushing's Disease
Conditions
Keywords
Cushing's disease, acromegaly, pasireotide, hyperglycemia
Brief summary
The study was designed to investigate the optimal management of hyperglycemia developed during pasireotide treatment in participants with Cushing's disease or Acromegaly, which was not manageable with metformin. This was a Phase IV, multi-center, randomized, open-label study. Eligible patients started pasireotide subcutaneously (s.c.) for Cushing's disease and pasireotide LAR (long-acting release) for Acromegaly. Participants being treated with pasireotide s.c or LAR at screening were eligible as long as they met protocol criteria during the screening period. If previously normo-glycemic participants experienced an increase in their fasting blood glucose and met the criteria for diabetes while on pasireotide, they started anti-diabetic treatment using metformin. If they continued to have elevated blood glucose above target on metformin within the first 16 weeks, they were randomized in a 1:1 ratio to receive treatment with incretin based therapy or insulin for approximately 16 weeks. Participants who continued to receive clinical benefit after completing the Core Phase could enter an optional Extension Phase if pasireotide was not commercially available in their country or a local access program was not available to provide drug. Patients continued in the Extension Phase until the last participant randomized in the Core Phase completed 16 weeks of treatment post-randomization.
Interventions
DRUGPasireotide s.c.
Administered to Cushing's disease participants.
DRUGSitagliptin
Taken for approximately 16 weeks during the core study phase or until the drug was found not to be effective
DRUGLiraglutide
Participant switched to liraglutide if sitagliptin was found not to be effective.
DRUGInsulin
Participant took insulin for 16 weeks. Insulin was also administered as rescue therapy in the incretin-based therapy arm if required. Insulin was administered to the BL-insulin group at the discretion of the Principal Investigator. Note: OAD and No OAD groups within the non-randomized arm did not take Insulin.
DRUGPasireotide LAR
Administered to Acromegaly participants.
DRUGMetformin
If previously normo-glycemic participants experienced increase in their fasting blood glucose and meeting the criteria for diabetes while on pasireotide, they started anti-diabetic treatment using metformin. If they continued to experience increase in their fasting blood glucose within the first 16 weeks, they were randomized in a 1:1 ratio to receive treatment with incretin based therapy or insulin for approximately 16 weeks. Metformin treatment was not required for the BL Insulin and OAD groups, within the non-randomized arm, but may have been prescribed at the discretion of the investigator. Note: No OAD group within the non-randomized arm did not take metformin.
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients greater than or equal to 18 years old * Confirmed diagnosis of Cushing's disease or acromegaly
Exclusion criteria
* Patients who require surgical intervention * Patients receiving DPP-4 inhibitors or GLP-1 receptor agonists within 4 weeks prior to study entry * HbA1c \> 10 % at screening * Known hypersensitivity to somatostatin analogues Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in HbA1c From Randomization to Approximately 16 Weeks | Randomization, 16 weeks | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in FPG (Fasting Plasma Glucose) From Randomization Until End of Core Phase | 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 | Absolute change in fasting glucose overtime from randomization (i.e. start of randomized antidiabetic treatment) to end of core phase per randomized arm |
| Percentage of Participants in the Incretin-based Arm Who Required Anti-diabetic Rescue Therapy With Insulin | Randomization to up to 16 weeks | The percentage of participants who received anti-diabetic rescue therapy in incretin based therapy is summarized. |
| Change in HbA1c From Randomization (R) Over Time Per Randomized Arm | 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) | Absolute change in HbA1c overtime from randomization (i.e. start of randomized antidiabetic treatment) to end of core phase per randomized arm |
| Absolute Change in FPG From Baseline to End of Core Phase | Baseline, Up to 32 weeks (end of Core Phase) | Absolute change in FPG from baseline to end of core phase in the incretin based therapy arm and the insulin arm. |
| Percentage of Participants With ≤ 0.3% HbA1c Increase to End of Core Phase | Randomization, up to 16 weeks | Percentage of participants with ≤ 0.3% HbA1c increase in the incretin based therapy arm and the insulin arm. |
| Absolute Change in HbA1c From Baseline to End of Core Phase | Baseline, up to 32 weeks (end of Core phase) | Absolute change in HbA1c from baseline to end of core phase in the incretin based therapy arm and the insulin arm |
Countries
Belgium, Brazil, China, Denmark, Germany, India, Peru, Poland, Russia, Thailand, Turkey (Türkiye), United States
Participant flow
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.
Participants by arm
| Arm | Count |
|---|---|
| Incretin Based Therapy (Randomized Group) 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 | 38 |
| Insulin (Randomized Group) 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. | 43 |
| Baseline Insulin (BL) (Non-randomized Group) This group included participants who were receiving insulin at study entry. | 19 |
| Oral Antidiabetic Drugs (OAD) (Non-randomized Group) 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. | 46 |
| No OAD (Non-randomized Group) 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. | 103 |
| Total | 249 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Core Phase | Administrative problems | 0 | 1 | 0 | 0 | 0 |
| Core Phase | Adverse Event | 2 | 0 | 0 | 2 | 6 |
| Core Phase | Protocol Violation | 0 | 0 | 0 | 1 | 0 |
| Core Phase | Unsatisfactory therapeutic effect | 1 | 5 | 0 | 0 | 0 |
| Core Phase | Withdrawal by Subject | 0 | 0 | 0 | 4 | 2 |
| Extension Phase | Administrative problems | 1 | 0 | 0 | 0 | 0 |
| Extension Phase | Adverse Event | 1 | 1 | 2 | 0 | 1 |
| Extension Phase | Death | 0 | 0 | 1 | 0 | 1 |
| Extension Phase | Protocol Violation | 0 | 0 | 0 | 0 | 1 |
| Extension Phase | Unsatisfactory therapeutic effect | 1 | 1 | 0 | 2 | 2 |
| Extension Phase | Withdrawal by Subject | 0 | 1 | 0 | 0 | 2 |
Baseline characteristics
| Characteristic | 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 |
|---|---|---|---|---|---|---|
| Age, Continuous | 50.6 Years STANDARD_DEVIATION 11.76 | 46.4 Years STANDARD_DEVIATION 12.9 | 46.7 Years STANDARD_DEVIATION 12.54 | 40.2 Years STANDARD_DEVIATION 13.8 | 37.8 Years STANDARD_DEVIATION 11.17 | 42.4 Years STANDARD_DEVIATION 13.05 |
| Race/Ethnicity, Customized Chinese | 5 Participants | 9 Participants | 1 Participants | 13 Participants | 33 Participants | 61 Participants |
| Race/Ethnicity, Customized Hispanic/Latino | 7 Participants | 2 Participants | 5 Participants | 6 Participants | 19 Participants | 39 Participants |
| Race/Ethnicity, Customized Indian (Indian subcontinent) | 4 Participants | 8 Participants | 2 Participants | 2 Participants | 7 Participants | 23 Participants |
| Race/Ethnicity, Customized Japanese | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Other | 22 Participants | 24 Participants | 11 Participants | 25 Participants | 43 Participants | 125 Participants |
| Sex: Female, Male Female | 22 Participants | 27 Participants | 10 Participants | 31 Participants | 47 Participants | 137 Participants |
| Sex: Female, Male Male | 16 Participants | 16 Participants | 9 Participants | 15 Participants | 56 Participants | 112 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 38 | 0 / 43 | 1 / 19 | 0 / 46 | 1 / 103 |
| other Total, other adverse events | 37 / 38 | 40 / 43 | 18 / 19 | 38 / 46 | 87 / 103 |
| serious Total, serious adverse events | 6 / 38 | 3 / 43 | 4 / 19 | 2 / 46 | 7 / 103 |
Outcome results
Primary
Change in HbA1c From Randomization to Approximately 16 Weeks
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
Population: 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 | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Incretin Based Therapy (Randomized Group) | Change in HbA1c From Randomization to Approximately 16 Weeks | All Patients | -0.12 Hba1c percentage |
| Incretin Based Therapy (Randomized Group) | Change in HbA1c From Randomization to Approximately 16 Weeks | Cushing's Disease | 0.33 Hba1c percentage |
| Incretin Based Therapy (Randomized Group) | Change in HbA1c From Randomization to Approximately 16 Weeks | Acromegaly | -0.25 Hba1c percentage |
| Insulin (Randomized Group) | Change in HbA1c From Randomization to Approximately 16 Weeks | All Patients | 0.26 Hba1c percentage |
| Insulin (Randomized Group) | Change in HbA1c From Randomization to Approximately 16 Weeks | Cushing's Disease | 0.45 Hba1c percentage |
| Insulin (Randomized Group) | Change in HbA1c From Randomization to Approximately 16 Weeks | Acromegaly | 0.19 Hba1c percentage |
Comparison: All Patients95% CI: [-0.63, 0.08]
Comparison: Cushing's Disease95% CI: [-0.96, 0.95]
Comparison: Acromegaly95% CI: [-0.74, 0.02]
Secondary
Absolute Change in FPG From Baseline to End of Core Phase
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)
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Incretin Based Therapy (Randomized Group) | Absolute Change in FPG From Baseline to End of Core Phase | Baseline: All Patients | 111.1 mg/dL | Standard Deviation 18.95 |
| Incretin Based Therapy (Randomized Group) | Absolute Change in FPG From Baseline to End of Core Phase | Change at EOP: All Patients | 22.2 mg/dL | Standard Deviation 31.67 |
| Incretin Based Therapy (Randomized Group) | Absolute Change in FPG From Baseline to End of Core Phase | Baseline: Cushing's | 117.9 mg/dL | Standard Deviation 20.99 |
| Incretin Based Therapy (Randomized Group) | Absolute Change in FPG From Baseline to End of Core Phase | Change at EOP: Cushing's | 13.4 mg/dL | Standard Deviation 34.92 |
| Incretin Based Therapy (Randomized Group) | Absolute Change in FPG From Baseline to End of Core Phase | Baseline: Acromegaly | 107.9 mg/dL | Standard Deviation 17.46 |
| Incretin Based Therapy (Randomized Group) | Absolute Change in FPG From Baseline to End of Core Phase | Change at EOP: Acromegaly | 26.5 mg/dL | Standard Deviation 29.79 |
| Insulin (Randomized Group) | Absolute Change in FPG From Baseline to End of Core Phase | Baseline: Acromegaly | 114.2 mg/dL | Standard Deviation 18.91 |
| Insulin (Randomized Group) | Absolute Change in FPG From Baseline to End of Core Phase | Change at EOP: Acromegaly | 16.7 mg/dL | Standard Deviation 33.29 |
| Insulin (Randomized Group) | Absolute Change in FPG From Baseline to End of Core Phase | Baseline: All Patients | 111.8 mg/dL | Standard Deviation 18.2 |
| Insulin (Randomized Group) | Absolute Change in FPG From Baseline to End of Core Phase | Baseline: Cushing's | 106.3 mg/dL | Standard Deviation 15.71 |
| Insulin (Randomized Group) | Absolute Change in FPG From Baseline to End of Core Phase | Change at EOP: Cushing's | 36.4 mg/dL | Standard Deviation 33.11 |
| Insulin (Randomized Group) | Absolute Change in FPG From Baseline to End of Core Phase | Change at EOP: All Patients | 22.5 mg/dL | Standard Deviation 34.05 |
| Baseline Insulin (BL) (Non-randomized Group) | Absolute Change in FPG From Baseline to End of Core Phase | Change at EOP: Cushing's | 21.3 mg/dL | Standard Deviation 72.01 |
| Baseline Insulin (BL) (Non-randomized Group) | Absolute Change in FPG From Baseline to End of Core Phase | Baseline: Acromegaly | 162.5 mg/dL | Standard Deviation 67.85 |
| Baseline Insulin (BL) (Non-randomized Group) | Absolute Change in FPG From Baseline to End of Core Phase | Baseline: All Patients | 157.7 mg/dL | Standard Deviation 66.5 |
| Baseline Insulin (BL) (Non-randomized Group) | Absolute Change in FPG From Baseline to End of Core Phase | Baseline: Cushing's | 147.2 mg/dL | Standard Deviation 68.38 |
| Baseline Insulin (BL) (Non-randomized Group) | Absolute Change in FPG From Baseline to End of Core Phase | Change at EOP: All Patients | 9.8 mg/dL | Standard Deviation 75.67 |
| Baseline Insulin (BL) (Non-randomized Group) | Absolute Change in FPG From Baseline to End of Core Phase | Change at EOP: Acromegaly | 4.6 mg/dL | Standard Deviation 79.57 |
| Oral Antidiabetic Drugs (OAD) (Non-randomized Group) | Absolute Change in FPG From Baseline to End of Core Phase | Change at EOP: Cushing's | 15.8 mg/dL | Standard Deviation 18.43 |
| Oral Antidiabetic Drugs (OAD) (Non-randomized Group) | Absolute Change in FPG From Baseline to End of Core Phase | Change at EOP: All Patients | 22.9 mg/dL | Standard Deviation 23.4 |
| Oral Antidiabetic Drugs (OAD) (Non-randomized Group) | Absolute Change in FPG From Baseline to End of Core Phase | Baseline: Cushing's | 93.3 mg/dL | Standard Deviation 10.98 |
| Oral Antidiabetic Drugs (OAD) (Non-randomized Group) | Absolute Change in FPG From Baseline to End of Core Phase | Change at EOP: Acromegaly | 25.8 mg/dL | Standard Deviation 24.82 |
| Oral Antidiabetic Drugs (OAD) (Non-randomized Group) | Absolute Change in FPG From Baseline to End of Core Phase | Baseline: Acromegaly | 98.8 mg/dL | Standard Deviation 15.2 |
| Oral Antidiabetic Drugs (OAD) (Non-randomized Group) | Absolute Change in FPG From Baseline to End of Core Phase | Baseline: All Patients | 97.2 mg/dL | Standard Deviation 14.24 |
| No OAD (Non-randomized Group) | Absolute Change in FPG From Baseline to End of Core Phase | Baseline: Acromegaly | 93.4 mg/dL | Standard Deviation 8.32 |
| No OAD (Non-randomized Group) | Absolute Change in FPG From Baseline to End of Core Phase | Baseline: Cushing's | 85.5 mg/dL | Standard Deviation 6.92 |
| No OAD (Non-randomized Group) | Absolute Change in FPG From Baseline to End of Core Phase | Change at EOP: All Patients | 16.3 mg/dL | Standard Deviation 13.63 |
| No OAD (Non-randomized Group) | Absolute Change in FPG From Baseline to End of Core Phase | Change at EOP: Acromegaly | 17.0 mg/dL | Standard Deviation 11.75 |
| No OAD (Non-randomized Group) | Absolute Change in FPG From Baseline to End of Core Phase | Change at EOP: Cushing's | 11.7 mg/dL | Standard Deviation 22.11 |
| No OAD (Non-randomized Group) | Absolute Change in FPG From Baseline to End of Core Phase | Baseline: All Patients | 92.2 mg/dL | Standard Deviation 8.58 |
Secondary
Absolute Change in HbA1c From Baseline to End of Core Phase
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)
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Incretin Based Therapy (Randomized Group) | Absolute Change in HbA1c From Baseline to End of Core Phase | Change at EOP: All Patients | 0.8 HbA1c percentage | Standard Deviation 0.97 |
| Incretin Based Therapy (Randomized Group) | Absolute Change in HbA1c From Baseline to End of Core Phase | Change at EOP: Acromegaly | 0.6 HbA1c percentage | Standard Deviation 0.78 |
| Incretin Based Therapy (Randomized Group) | Absolute Change in HbA1c From Baseline to End of Core Phase | Baseline: Cushing's | 6.6 HbA1c percentage | Standard Deviation 0.87 |
| Incretin Based Therapy (Randomized Group) | Absolute Change in HbA1c From Baseline to End of Core Phase | Baseline: Acromegaly | 6.1 HbA1c percentage | Standard Deviation 0.71 |
| Incretin Based Therapy (Randomized Group) | Absolute Change in HbA1c From Baseline to End of Core Phase | Baseline: All Patients | 6.3 HbA1c percentage | Standard Deviation 0.8 |
| Incretin Based Therapy (Randomized Group) | Absolute Change in HbA1c From Baseline to End of Core Phase | Change at EOP: Cushing's | 1.3 HbA1c percentage | Standard Deviation 1.19 |
| Insulin (Randomized Group) | Absolute Change in HbA1c From Baseline to End of Core Phase | Baseline: All Patients | 6.3 HbA1c percentage | Standard Deviation 0.63 |
| Insulin (Randomized Group) | Absolute Change in HbA1c From Baseline to End of Core Phase | Change at EOP: Acromegaly | 0.8 HbA1c percentage | Standard Deviation 0.78 |
| Insulin (Randomized Group) | Absolute Change in HbA1c From Baseline to End of Core Phase | Change at EOP: All Patients | 1.1 HbA1c percentage | Standard Deviation 0.94 |
| Insulin (Randomized Group) | Absolute Change in HbA1c From Baseline to End of Core Phase | Baseline: Cushing's | 6.5 HbA1c percentage | Standard Deviation 0.58 |
| Insulin (Randomized Group) | Absolute Change in HbA1c From Baseline to End of Core Phase | Change at EOP: Cushing's | 1.7 HbA1c percentage | Standard Deviation 1.05 |
| Insulin (Randomized Group) | Absolute Change in HbA1c From Baseline to End of Core Phase | Baseline: Acromegaly | 6.3 HbA1c percentage | Standard Deviation 0.65 |
| Baseline Insulin (BL) (Non-randomized Group) | Absolute Change in HbA1c From Baseline to End of Core Phase | Baseline: Cushing's | 6.9 HbA1c percentage | Standard Deviation 0.92 |
| Baseline Insulin (BL) (Non-randomized Group) | Absolute Change in HbA1c From Baseline to End of Core Phase | Baseline: Acromegaly | 8.0 HbA1c percentage | Standard Deviation 1.61 |
| Baseline Insulin (BL) (Non-randomized Group) | Absolute Change in HbA1c From Baseline to End of Core Phase | Change at EOP: Acromegaly | 1.2 HbA1c percentage | Standard Deviation 1.37 |
| Baseline Insulin (BL) (Non-randomized Group) | Absolute Change in HbA1c From Baseline to End of Core Phase | Baseline: All Patients | 7.7 HbA1c percentage | Standard Deviation 1.51 |
| Baseline Insulin (BL) (Non-randomized Group) | Absolute Change in HbA1c From Baseline to End of Core Phase | Change at EOP: Cushing's | 1.4 HbA1c percentage | Standard Deviation 1.58 |
| Baseline Insulin (BL) (Non-randomized Group) | Absolute Change in HbA1c From Baseline to End of Core Phase | Change at EOP: All Patients | 1.3 HbA1c percentage | Standard Deviation 1.4 |
| Oral Antidiabetic Drugs (OAD) (Non-randomized Group) | Absolute Change in HbA1c From Baseline to End of Core Phase | Change at EOP: Cushing's | 0.9 HbA1c percentage | Standard Deviation 0.95 |
| Oral Antidiabetic Drugs (OAD) (Non-randomized Group) | Absolute Change in HbA1c From Baseline to End of Core Phase | Baseline: Cushing's | 5.9 HbA1c percentage | Standard Deviation 0.49 |
| Oral Antidiabetic Drugs (OAD) (Non-randomized Group) | Absolute Change in HbA1c From Baseline to End of Core Phase | Baseline: Acromegaly | 5.6 HbA1c percentage | Standard Deviation 0.36 |
| Oral Antidiabetic Drugs (OAD) (Non-randomized Group) | Absolute Change in HbA1c From Baseline to End of Core Phase | Change at EOP: Acromegaly | 0.7 HbA1c percentage | Standard Deviation 0.47 |
| Oral Antidiabetic Drugs (OAD) (Non-randomized Group) | Absolute Change in HbA1c From Baseline to End of Core Phase | Change at EOP: All Patients | 0.8 HbA1c percentage | Standard Deviation 0.64 |
| Oral Antidiabetic Drugs (OAD) (Non-randomized Group) | Absolute Change in HbA1c From Baseline to End of Core Phase | Baseline: All Patients | 5.7 HbA1c percentage | Standard Deviation 0.41 |
| No OAD (Non-randomized Group) | Absolute Change in HbA1c From Baseline to End of Core Phase | Change at EOP: Acromegaly | 0.4 HbA1c percentage | Standard Deviation 0.28 |
| No OAD (Non-randomized Group) | Absolute Change in HbA1c From Baseline to End of Core Phase | Baseline: All Patients | 5.4 HbA1c percentage | Standard Deviation 0.33 |
| No OAD (Non-randomized Group) | Absolute Change in HbA1c From Baseline to End of Core Phase | Change at EOP: All Patients | 0.4 HbA1c percentage | Standard Deviation 0.32 |
| No OAD (Non-randomized Group) | Absolute Change in HbA1c From Baseline to End of Core Phase | Baseline: Cushing's | 5.5 HbA1c percentage | Standard Deviation 0.41 |
| No OAD (Non-randomized Group) | Absolute Change in HbA1c From Baseline to End of Core Phase | Change at EOP: Cushing's | 0.5 HbA1c percentage | Standard Deviation 0.51 |
| No OAD (Non-randomized Group) | Absolute Change in HbA1c From Baseline to End of Core Phase | Baseline: Acromegaly | 5.4 HbA1c percentage | Standard Deviation 0.32 |
Secondary
Change in FPG (Fasting Plasma Glucose) From Randomization Until End of Core Phase
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
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Incretin Based Therapy (Randomized Group) | Change in FPG (Fasting Plasma Glucose) From Randomization Until End of Core Phase | Randomization | 172.2 mg/dL | Standard Deviation 60.78 |
| Incretin Based Therapy (Randomized Group) | Change in FPG (Fasting Plasma Glucose) From Randomization Until End of Core Phase | Change at RW2 D15 | 4.6 mg/dL | Standard Deviation 51.01 |
| Incretin Based Therapy (Randomized Group) | Change in FPG (Fasting Plasma Glucose) From Randomization Until End of Core Phase | Change at RW4 D29 | -15.0 mg/dL | Standard Deviation 47.95 |
| Incretin Based Therapy (Randomized Group) | Change in FPG (Fasting Plasma Glucose) From Randomization Until End of Core Phase | Change at RW6 D43 | -17.7 mg/dL | Standard Deviation 57.97 |
| Incretin Based Therapy (Randomized Group) | Change in FPG (Fasting Plasma Glucose) From Randomization Until End of Core Phase | Change at RW8 D57 | -25.7 mg/dL | Standard Deviation 53.32 |
| Incretin Based Therapy (Randomized Group) | Change in FPG (Fasting Plasma Glucose) From Randomization Until End of Core Phase | Change at RW10 D71 | -28.8 mg/dL | Standard Deviation 61.14 |
| Incretin Based Therapy (Randomized Group) | Change in FPG (Fasting Plasma Glucose) From Randomization Until End of Core Phase | Change at RW12 D85 | -33.4 mg/dL | Standard Deviation 50.17 |
| Incretin Based Therapy (Randomized Group) | Change in FPG (Fasting Plasma Glucose) From Randomization Until End of Core Phase | Change at RW14 D99 | -35.1 mg/dL | Standard Deviation 55.83 |
| Incretin Based Therapy (Randomized Group) | Change in FPG (Fasting Plasma Glucose) From Randomization Until End of Core Phase | Change at RW16 D113 | -38.8 mg/dL | Standard Deviation 53.69 |
| Incretin Based Therapy (Randomized Group) | Change in FPG (Fasting Plasma Glucose) From Randomization Until End of Core Phase | End of Core Phase | -40.1 mg/dL | Standard Deviation 56.35 |
| Insulin (Randomized Group) | Change in FPG (Fasting Plasma Glucose) From Randomization Until End of Core Phase | Change at RW14 D99 | -35.6 mg/dL | Standard Deviation 47.43 |
| Insulin (Randomized Group) | Change in FPG (Fasting Plasma Glucose) From Randomization Until End of Core Phase | Randomization | 167.9 mg/dL | Standard Deviation 40.77 |
| Insulin (Randomized Group) | Change in FPG (Fasting Plasma Glucose) From Randomization Until End of Core Phase | Change at RW10 D71 | -36.9 mg/dL | Standard Deviation 50.82 |
| Insulin (Randomized Group) | Change in FPG (Fasting Plasma Glucose) From Randomization Until End of Core Phase | Change at RW2 D15 | -31.1 mg/dL | Standard Deviation 41.19 |
| Insulin (Randomized Group) | Change in FPG (Fasting Plasma Glucose) From Randomization Until End of Core Phase | End of Core Phase | -36.0 mg/dL | Standard Deviation 46.9 |
| Insulin (Randomized Group) | Change in FPG (Fasting Plasma Glucose) From Randomization Until End of Core Phase | Change at RW4 D29 | -28.3 mg/dL | Standard Deviation 41.14 |
| Insulin (Randomized Group) | Change in FPG (Fasting Plasma Glucose) From Randomization Until End of Core Phase | Change at RW12 D85 | -41.1 mg/dL | Standard Deviation 51.68 |
| Insulin (Randomized Group) | Change in FPG (Fasting Plasma Glucose) From Randomization Until End of Core Phase | Change at RW6 D43 | -37.5 mg/dL | Standard Deviation 52.39 |
| Insulin (Randomized Group) | Change in FPG (Fasting Plasma Glucose) From Randomization Until End of Core Phase | Change at RW16 D113 | -33.4 mg/dL | Standard Deviation 47.63 |
| Insulin (Randomized Group) | Change in FPG (Fasting Plasma Glucose) From Randomization Until End of Core Phase | Change at RW8 D57 | -38.3 mg/dL | Standard Deviation 44.1 |
Secondary
Change in HbA1c From Randomization (R) Over Time Per Randomized Arm
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)
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Incretin Based Therapy (Randomized Group) | Change in HbA1c From Randomization (R) Over Time Per Randomized Arm | Randomization | 7.1 HbA1c percentage | Standard Deviation 1 |
| Incretin Based Therapy (Randomized Group) | Change in HbA1c From Randomization (R) Over Time Per Randomized Arm | Change at RW4 D29 | 0.5 HbA1c percentage | Standard Deviation 0.73 |
| Incretin Based Therapy (Randomized Group) | Change in HbA1c From Randomization (R) Over Time Per Randomized Arm | Change at RW8 D57 | 0.3 HbA1c percentage | Standard Deviation 0.98 |
| Incretin Based Therapy (Randomized Group) | Change in HbA1c From Randomization (R) Over Time Per Randomized Arm | Change at RW12 D85 | 0.2 HbA1c percentage | Standard Deviation 1.03 |
| Incretin Based Therapy (Randomized Group) | Change in HbA1c From Randomization (R) Over Time Per Randomized Arm | Change at RW16 D113 | 0.0 HbA1c percentage | Standard Deviation 0.93 |
| Incretin Based Therapy (Randomized Group) | Change in HbA1c From Randomization (R) Over Time Per Randomized Arm | End of Core Phase | 0.0 HbA1c percentage | Standard Deviation 0.92 |
| Insulin (Randomized Group) | Change in HbA1c From Randomization (R) Over Time Per Randomized Arm | Change at RW16 D113 | 0.3 HbA1c percentage | Standard Deviation 0.87 |
| Insulin (Randomized Group) | Change in HbA1c From Randomization (R) Over Time Per Randomized Arm | Randomization | 7.1 HbA1c percentage | Standard Deviation 0.75 |
| Insulin (Randomized Group) | Change in HbA1c From Randomization (R) Over Time Per Randomized Arm | Change at RW12 D85 | 0.4 HbA1c percentage | Standard Deviation 0.85 |
| Insulin (Randomized Group) | Change in HbA1c From Randomization (R) Over Time Per Randomized Arm | Change at RW4 D29 | 0.5 HbA1c percentage | Standard Deviation 0.6 |
| Insulin (Randomized Group) | Change in HbA1c From Randomization (R) Over Time Per Randomized Arm | End of Core Phase | 0.3 HbA1c percentage | Standard Deviation 0.84 |
| Insulin (Randomized Group) | Change in HbA1c From Randomization (R) Over Time Per Randomized Arm | Change at RW8 D57 | 0.5 HbA1c percentage | Standard Deviation 0.86 |
Secondary
Percentage of Participants in the Incretin-based Arm Who Required Anti-diabetic Rescue Therapy With Insulin
The percentage of participants who received anti-diabetic rescue therapy in incretin based therapy is summarized.
Time frame: Randomization to up to 16 weeks
Population: 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 | Measure | Value (NUMBER) |
|---|---|---|
| Incretin Based Therapy (Randomized Group) | Percentage of Participants in the Incretin-based Arm Who Required Anti-diabetic Rescue Therapy With Insulin | 31.6 Percentage of participants |
Secondary
Percentage of Participants With ≤ 0.3% HbA1c Increase to End of Core Phase
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
Population: 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 | Measure | Value (NUMBER) |
|---|---|---|
| Incretin Based Therapy (Randomized Group) | Percentage of Participants With ≤ 0.3% HbA1c Increase to End of Core Phase | 73.7 Percentage of participants |
| Insulin (Randomized Group) | Percentage of Participants With ≤ 0.3% HbA1c Increase to End of Core Phase | 65.1 Percentage of participants |