Study of Management of Pasireotide-induced Hyperglycemia in Adult Patients With Cushing's Disease or Acromegaly
Condition: Cushing's Disease; Acromegaly
MeSH terms: ACTH-Secreting Pituitary Adenoma; Acromegaly; Pituitary ACTH Hypersecretion; Hyperglycemia
Intervention: Pasireotide s.c.; Sitagliptin; Liraglutide; Insulin; Pasireotide LAR; Metformin
Intervention description: 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.
Intervention MeSH terms: Metformin; Sitagliptin Phosphate; Liraglutide; Pasireotide; Somatostatin
Phase: Phase 4
Study type: Interventional
Primary purpose: Supportive Care
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 249.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Cushing's disease; acromegaly; pasireotide; hyperglycemia

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.
    

Eligibility criteria:

        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/exclusion criteria may apply.