Study of Management of Pasireotide-induced Hyperglycemia in Adult Patients With Cushing's Disease or Acromegaly
- Conditions
- Cushing's DiseaseAcromegaly
- Interventions
- Registration Number
- NCT02060383
- Lead Sponsor
- Novartis Pharmaceuticals
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 249
- Patients greater than or equal to 18 years old
- Confirmed diagnosis of Cushing's disease or acromegaly
- 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/exclusion criteria may apply.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Non-Randomized Arm Pasireotide s.c. This arm represents the non-randomized participants: Cushing's Disease (CD) or Acromegaly participants, who received pasireotide s.c. or LAR (long-acting release) respectively, but who were not randomized to the Incretin or Insulin arms. For the purpose of analysis, this non-randomized arm is further split into 3 groups: * Baseline insulin group (BL insulin) includes participants who were receiving insulin at study entry * Oral antidiabetic drugs (OAD) group includes participants who developed hyperglycemia that was controlled by metformin and/or other background anti-diabetic treatment * No OAD group includes participants who did not receive any anti-diabetic medication during the core phase of the trial Incretin based therapy (randomized group) Pasireotide LAR 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. Incretin based therapy (randomized group) Pasireotide s.c. 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. Insulin (randomized group) Pasireotide s.c. 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. Non-Randomized Arm Insulin This arm represents the non-randomized participants: Cushing's Disease (CD) or Acromegaly participants, who received pasireotide s.c. or LAR (long-acting release) respectively, but who were not randomized to the Incretin or Insulin arms. For the purpose of analysis, this non-randomized arm is further split into 3 groups: * Baseline insulin group (BL insulin) includes participants who were receiving insulin at study entry * Oral antidiabetic drugs (OAD) group includes participants who developed hyperglycemia that was controlled by metformin and/or other background anti-diabetic treatment * No OAD group includes participants who did not receive any anti-diabetic medication during the core phase of the trial Insulin (randomized group) Pasireotide LAR 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. Non-Randomized Arm Pasireotide LAR This arm represents the non-randomized participants: Cushing's Disease (CD) or Acromegaly participants, who received pasireotide s.c. or LAR (long-acting release) respectively, but who were not randomized to the Incretin or Insulin arms. For the purpose of analysis, this non-randomized arm is further split into 3 groups: * Baseline insulin group (BL insulin) includes participants who were receiving insulin at study entry * Oral antidiabetic drugs (OAD) group includes participants who developed hyperglycemia that was controlled by metformin and/or other background anti-diabetic treatment * No OAD group includes participants who did not receive any anti-diabetic medication during the core phase of the trial Incretin based therapy (randomized group) Insulin 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. Insulin (randomized group) 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. Incretin based therapy (randomized group) Sitagliptin 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. Incretin based therapy (randomized group) Liraglutide 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. Incretin based therapy (randomized group) Metformin 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. Insulin (randomized group) Metformin 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. Non-Randomized Arm Metformin This arm represents the non-randomized participants: Cushing's Disease (CD) or Acromegaly participants, who received pasireotide s.c. or LAR (long-acting release) respectively, but who were not randomized to the Incretin or Insulin arms. For the purpose of analysis, this non-randomized arm is further split into 3 groups: * Baseline insulin group (BL insulin) includes participants who were receiving insulin at study entry * Oral antidiabetic drugs (OAD) group includes participants who developed hyperglycemia that was controlled by metformin and/or other background anti-diabetic treatment * No OAD group includes participants who did not receive any anti-diabetic medication during the core phase of the trial
- Primary Outcome Measures
Name Time Method 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 Outcome Measures
Name Time Method 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
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
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.
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
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.
Trial Locations
- Locations (16)
LA Biomedical Research at Harbor UCLA Medical Center SC - SOM230B2219
🇺🇸Torrance, California, United States
Diabetes and Endocrine Associates La Mesa Location
🇺🇸Multiple Locations, California, United States
East Coast Institute for Research East Coast Inst. for Res(ECIR)
🇺🇸Jacksonville, Florida, United States
Coastal Metabolic Research Centre SC
🇺🇸Ventura, California, United States
Washington University SC - SOM230B2411
🇺🇸Saint Louis, Missouri, United States
Robert Wood Johnson Medical School - Rutgers SC
🇺🇸New Brunswick, New Jersey, United States
The Mount Sinai Hospital SC
🇺🇸New York, New York, United States
Lenox Hill Hospital/Manhattan Eye, Ear and Throat Hospital SC
🇺🇸New York, New York, United States
Columbia University Medical Center New York Presbyterian Neuroendocrine Unit
🇺🇸New York, New York, United States
Virginia Endocrinology Research SC-2
🇺🇸Chesapeake, Virginia, United States
Allegheny Endocrinology Associates SC
🇺🇸Pittsburgh, Pennsylvania, United States
Baylor College of Medicine Ben Taub General Hosp.
🇺🇸Houston, Texas, United States
Swedish Medical Center Dept.ofSeattle Neuroscience(2)
🇺🇸Seattle, Washington, United States
Great Falls Clinic
🇺🇸Great Falls, Montana, United States
Novartis Investigative Site
🇹🇷Antalya, Turkey
Vanderbilt Clinical Trials Center SOM230B2219
🇺🇸Nashville, Tennessee, United States