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

Novartis

Status and phase: Completed; Phase 4

Conditions: Cushing's Disease; Acromegaly

Treatments: Drug: Pasireotide s.c.; Drug: Liraglutide; Drug: Pasireotide LAR; Drug: Metformin; Drug: Insulin; Drug: Sitagliptin

Study type: Interventional

Funder types: Industry

Identifiers

NCT02060383

CSOM230B2219

2012-002916-16 (EudraCT Number)

Details and patient eligibility

About

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.

Enrollment: 249 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Supportive Care

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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249 participants in 3 patient groups

Incretin based therapy (randomized group)

Experimental 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.

Treatment:

Drug: Sitagliptin

Drug: Insulin

Drug: Metformin

Drug: Liraglutide

Drug: Pasireotide LAR

Drug: Pasireotide s.c.

Insulin (randomized group)

Experimental group

Description:

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.

Treatment:

Drug: Insulin

Drug: Metformin

Drug: Pasireotide LAR

Drug: Pasireotide s.c.

Non-Randomized Arm

Other group

Description:

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

Treatment:

Drug: Insulin

Drug: Metformin

Drug: Pasireotide LAR

Drug: Pasireotide s.c.