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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
SUPPORTIVE_CARE
Masking
NONE
Enrollment
249
Administered to Cushing's disease participants.
Taken for approximately 16 weeks during the core study phase or until the drug was found not to be effective
Participant switched to liraglutide if sitagliptin was found not to be effective.
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.
Administered to Acromegaly participants.
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.
Diabetes and Endocrine Associates La Mesa Location
Multiple Locations, California, United States
LA Biomedical Research at Harbor UCLA Medical Center SC - SOM230B2219
Torrance, California, United States
Coastal Metabolic Research Centre SC
Ventura, California, United States
East Coast Institute for Research East Coast Inst. for Res(ECIR)
Jacksonville, Florida, United States
Washington University SC - SOM230B2411
St Louis, Missouri, United States
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
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)
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
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
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)
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)
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
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