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

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

Overview[ - collapse ][ - ]

Purpose	The study aims to demonstrate that pasireotide-induced hyperglycemia can be effectively and safely managed in majority of patients, including those with diabetes at start of pasireotide treatment.
Condition	Cushing's Disease, Acromegaly
Intervention	Drug: Pasireotide s.c. Drug: Sitagliptin Drug: Liraglutide Drug: Insulin Drug: Pasireotide LAR Drug: Metformin
Phase	Phase 4
Sponsor	Novartis Pharmaceuticals
Responsible Party	Novartis
ClinicalTrials.gov Identifier	NCT02060383
First Received	February 10, 2014
Last Updated	February 11, 2014
Last verified	February 2014

Tracking Information[ + expand ][ + ]

First Received Date	February 10, 2014
Last Updated Date	February 11, 2014
Start Date	March 2014
Estimated Primary Completion Date	May 2017
Current Primary Outcome Measures	Change in HbA1c from randomization to approximately 16 weeks [Time Frame: Randomization, 16 weeks] [Designated as safety issue: No]HbA1c change from randomization to approximately 16 weeks in the incretin based therapy arm and insulin arm.
Current Secondary Outcome Measures	Change in HbA1c and FPG (Fasting Plasma Glucose) from randomization over time and to Core EOP (End of Phase) (only for FPG) 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] [Designated as safety issue: No]The change in HbA1c and FPG from randomization overtime and to the core EOP (only for FPG) will be summarized for each randomized arm. Proportion of patients who required anti-diabetic rescue therapy with insulin in the incretin based arm [Time Frame: Randomization to up to 16 weeks] [Designated as safety issue: No]The proportion of patients who received anti-diabetic rescue therapy in incretin based therapy will be summarized. Change in HbA1c and FPG from baseline to Core EOP [Time Frame: Baseline, Up to 32 weeks] [Designated as safety issue: No]Change in HbA1c and FPG from baseline to Core EOP in patients who received pasireotide by treatment group Proportion of patients with ≤ 0.3% HbA1c increase from baseline to Core EOP per randomized arm. [Time Frame: Baseline, Up to 32 weeks] [Designated as safety issue: No]The proportion of patients with an increase from baseline in HbA1c ≤ 0.3% at Core EOP will be summarized for each randomized arm. Safety and tolerability of pasireotide and anti-diabetic treatments [Time Frame: Up to 32 weeks] [Designated as safety issue: Yes]Number of adverse drug events, overall and by severity and number of serious adverse events and laboratory abnormalities. Also, changes in laboratory assessments, electrocardiograms, vital signs, thyroid function tests and gallbladder examinations Incidence of hypoglycemia events [Time Frame: Up to 32 weeks] [Designated as safety issue: Yes]Summary of the number of treatment emergent hypoglycemia events, as well as the number of patients with hypoglycemia events.

Descriptive Information[ + expand ][ + ]

Brief Title	Study of Management of Pasireotide-induced Hyperglycemia in Adult Patients With Cushing's Disease or Acromegaly
Official Title	A Multi-center, Randomized, Open-label, Phase IV Study to Investigate the Management of Pasireotide-induced Hyperglycemia With Incretin Based Therapy or Insulin in Adult Patients With Cushing's Disease or Acromegaly
Brief Summary	The study aims to demonstrate that pasireotide-induced hyperglycemia can be effectively and safely managed in majority of patients, including those with diabetes at start of pasireotide treatment.
Detailed Description	This is a Phase IV, multi-center, randomized, open-label study. Eligible patients will start pasireotide subcutaneously (s.c.) for Cushing's disease and pasireotide LAR (long-acting release) for acromegaly. Patients currently treated at screening visit with pasireotide s.c. or LAR are eligible as long as they meet protocol criteria during the screening period. If previously normo-glycemic patients experience increases in their fasting blood glucose and meeting the criteria for diabetes while on pasireotide, they will start anti-diabetic treatment using metformin. If they continue to have elevated blood sugars above target on metformin within the first 16 weeks, they will be randomized in a 1:1 ratio to receive treatment with incretin based therapy or insulin for approximately 16 weeks.
Study Type	Interventional
Study Phase	Phase 4
Study Design	Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Supportive Care
Condition	Cushing's Disease, Acromegaly
Intervention	Drug: Pasireotide s.c. To be administered to Cushing's patients Drug: Sitagliptin Taken for 16 weeks or until the drug is found to be not effective Drug: Liraglutide Patient will switch to liraglutide if sitagliptin is found to be inefficacious. Drug: Insulin Patient will take insulin for 16 weeks. Drug: Pasireotide LAR To be administered to acromegaly patients Drug: Metformin If previously normo-glycemic patients experience increases in their fasting blood glucose and meeting the criteria for diabetes while on pasireotide, they will start anti-diabetic treatment using metformin. If they continue to experience increases in their fasting blood glucose within the first 16 weeks, they will be randomized in a 1:1 ratio to receive treatment with incretin based therapy or insulin for approximately 16 weeks.
Study Arm (s)	Other: Incretin based therapy Patients randomized to the incretin based arm will start with sitagliptin once daily. If sitagliptin does not control the patient's hyperglycemia, sitagliptin will be stopped and patients will be switched to liraglutide once daily. Other: Insulin Patients randomized to the insulin arm may start with once daily dose of basal insulin. The dose may be up or down titrated at the discretion of the investigator. If blood glucose levels remain uncontrolled on basal insulin, patient may be switched to basal insulin plus prandial insulin.

Recruitment Information[ + expand ][ + ]

Recruitment Status	Not yet recruiting
Estimated Enrollment	133
Estimated Completion Date	May 2017
Estimated Primary Completion Date	May 2017
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.
Gender	Both
Ages	18 Years
Accepts Healthy Volunteers	No
Contacts	Contact: Novartis Pharmaceuticals +41613241111
Location Countries	United States, Denmark, Germany

Administrative Information[ + expand ][ + ]

NCT Number	NCT02060383
Other Study ID Numbers	CSOM230B2219
Has Data Monitoring Committee	No
Information Provided By	Novartis
Study Sponsor	Novartis Pharmaceuticals
Collaborators	Not Provided
Investigators	Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
Verification Date	February 2014

Locations[ + expand ][ + ]

Columbia University Medical Center- New York Presbyterian Neuroendocrine Unit	New York, New York, United States, 10032 Contact: Jean Carlos Fernandez \| +1 212 305 4921 \| sjf2132@cumc.columbia.edu Principal Investigator: Pamela U. Freda Not yet recruiting
Vanderbilt Clinical Trials Center SOM230B2219	Nashville, Tennessee, United States, 37212-8210 Contact: Sheri Dixon \| 615-343-0266 \| sheri.dixon@vanderbilt.edu Principal Investigator: Andrea Utz Not yet recruiting
Novartis Investigative Site	Arhus, Denmark, 8000 Not yet recruiting
Novartis Investigative Site	Erlangen, Germany, 91054 Not yet recruiting
Novartis Investigative Site	München, Germany, 80336 Not yet recruiting