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

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by Novartis
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT02060383
First received: February 10, 2014
Last updated: July 16, 2014
Last verified: July 2014
  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 Intervention Phase
Cushing's Disease,
Acromegaly
Drug: Pasireotide s.c.
Drug: Sitagliptin
Drug: Liraglutide
Drug: Insulin
Drug: Pasireotide LAR
Drug: Metformin
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Supportive Care
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

Resource links provided by NLM:


Further study details as provided by Novartis:

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.


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.


Estimated Enrollment: 133
Study Start Date: May 2014
Estimated Study Completion Date: June 2017
Estimated Primary Completion Date: June 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
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: 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.
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.
Drug: Pasireotide s.c.
To be administered to Cushing's patients
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.

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02060383

Contacts
Contact: Novartis Pharmaceuticals 1-888-669-6682
Contact: Novartis Pharmaceuticals

Locations
United States, Arizona
ClinTriCo Not yet recruiting
Phoenix, Arizona, United States, 85083
Contact: Amber Ackerlund    623-240-2370    aackerlund@clintrico.com   
Principal Investigator: Chioma Iweha         
United States, New York
SUNY Downstate Health Science Center SC - SOM230B2219 Not yet recruiting
Brooklyn, New York, United States, 11203
Contact: John Allen       john.allen@downstate.edu   
Principal Investigator: Mary Ann Banerji         
Columbia University Medical Center- New York Presbyterian Neuroendocrine Unit Recruiting
New York, New York, United States, 10032
Contact: Carlos C. Reyes-Vidal    212-305-4921    csr52@cumc.columbia.edu   
Principal Investigator: Pamela U. Freda         
United States, Rhode Island
R. I. Hospital Medical Oncology Clinical Research SC Withdrawn
Providence, Rhode Island, United States, 02903
United States, Tennessee
Vanderbilt Clinical Trials Center SOM230B2219 Not yet recruiting
Nashville, Tennessee, United States, 37212-8210
Contact: Sheri L. Dixon    615-343-0266    sheri.dixon@vanderbilt.edu   
Principal Investigator: Andrea Utz         
United States, Texas
Baylor College of Medicine Ben Taub General Hosp. Not yet recruiting
Houston, Texas, United States, 77030
Contact: Michael George    713-873-8772    stauding@bcm.edu   
Principal Investigator: Susan L. Samson         
United States, Washington
Swedish Medical Center Dept.ofSeattle Neuroscience(2) Not yet recruiting
Seattle, Washington, United States
Contact: Becky Wood    206-320-7115    becky.wood@swedish.org   
Principal Investigator: Frances Broyles         
Denmark
Novartis Investigative Site Not yet recruiting
Aalborg, Denmark, 9000
Novartis Investigative Site Not yet recruiting
Copenhagen Ø, Denmark, 2100
Novartis Investigative Site Not yet recruiting
Herlev, Denmark, 2730
Novartis Investigative Site Not yet recruiting
Odense C, Denmark, DK-5000
Novartis Investigative Site Not yet recruiting
Århus, Denmark, DK-8000
Germany
Novartis Investigative Site Not yet recruiting
Erlangen, Germany, 91054
Novartis Investigative Site Not yet recruiting
München, Germany, 80336
Russian Federation
Novartis Investigative Site Not yet recruiting
Barnaul, Russian Federation, 656024
Novartis Investigative Site Not yet recruiting
Moscow, Russian Federation, 117036
Novartis Investigative Site Not yet recruiting
Moscow, Russian Federation, 129110
Novartis Investigative Site Not yet recruiting
Saint-Petersburg, Russian Federation, 197341
Turkey
Novartis Investigative Site Not yet recruiting
Altunizade, Turkey, 34662
Novartis Investigative Site Not yet recruiting
Ankara, Turkey, 06500
Novartis Investigative Site Not yet recruiting
Antalya, Turkey, 07070
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

No publications provided

Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT02060383     History of Changes
Other Study ID Numbers: CSOM230B2219, 2012-002916-16
Study First Received: February 10, 2014
Last Updated: July 16, 2014
Health Authority: United States: Food and Drug Administration
China: Food and Drug Administration
Denmark: Danish Medicines Agency
Germany: Federal Institute for Drugs and Medical Devices
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Russia: Ministry of Health of the Russian Federation
Turkey: Ministry of Health

Keywords provided by Novartis:
Cushing's disease,
acromegaly,
pasireotide,
hyperglycemia

Additional relevant MeSH terms:
Acromegaly
Hyperglycemia
Cushing Syndrome
Pituitary ACTH Hypersecretion
Glucose Metabolism Disorders
Metabolic Diseases
Bone Diseases, Endocrine
Bone Diseases
Musculoskeletal Diseases
Hyperpituitarism
Pituitary Diseases
Hypothalamic Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Endocrine System Diseases
Adrenocortical Hyperfunction
Adrenal Gland Diseases
Insulin, Globin Zinc
Sitagliptin
Liraglutide
Metformin
Insulin
Incretins
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Dipeptidyl-Peptidase IV Inhibitors

ClinicalTrials.gov processed this record on September 18, 2014