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

Acromegaly Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02060383
• Other study ID #: CSOM230B2219
• Secondary ID: 2012-002916-16
• Status: Completed
• Phase: Phase 4
• Start date: May 23, 2014
• Est. completion date: March 26, 2018

Study information

• Verified date: May 2019
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 249
• Est. completion date: March 26, 2018
• Est. primary completion date: February 5, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Acromegaly
• ACTH-Secreting Pituitary Adenoma
• Cushing's Disease
• Hyperglycemia
• Pituitary ACTH Hypersecretion

Intervention

Drug:
• Pasireotide s.c.
Administered to Cushing's disease participants.
• Sitagliptin
Taken for approximately 16 weeks during the core study phase or until the drug was found not to be effective
• Liraglutide
Participant switched to liraglutide if sitagliptin was found not to be effective.
• Insulin
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.
• Pasireotide LAR
Administered to Acromegaly participants.
• Metformin
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.

Locations

Country	Name	City	State
Belgium	Novartis Investigative Site	Leuven
Belgium	Novartis Investigative Site	Wilrijk
Brazil	Novartis Investigative Site	Joinville	SC
Brazil	Novartis Investigative Site	Porto Alegre	RS
Brazil	Novartis Investigative Site	Rio de Janeiro	RJ
Brazil	Novartis Investigative Site	São Paulo	SP
China	Novartis Investigative Site	Beijing	Beijing
China	Novartis Investigative Site	Chengdu	Sichuan
China	Novartis Investigative Site	Guangzhou	Guangdong
Denmark	Novartis Investigative Site	Aalborg
Denmark	Novartis Investigative Site	Aarhus
Denmark	Novartis Investigative Site	Herlev
Denmark	Novartis Investigative Site	Odense C
Germany	Novartis Investigative Site	Erlangen
Germany	Novartis Investigative Site	Freiburg
Germany	Novartis Investigative Site	Oldenburg
India	Novartis Investigative Site	Bangalore	Karnataka
India	Novartis Investigative Site	Vellore	Tamil Nadu
Peru	Novartis Investigative Site	San Isidro	Lima
Poland	Novartis Investigative Site	Warszawa
Poland	Novartis Investigative Site	Wroclaw
Russian Federation	Novartis Investigative Site	Saint Petersburg
Thailand	Novartis Investigative Site	Bangkok
Thailand	Novartis Investigative Site	Bangkok
Thailand	Novartis Investigative Site	Songkla
Turkey	Novartis Investigative Site	Altunizade
Turkey	Novartis Investigative Site	Ankara
Turkey	Novartis Investigative Site	Antalya
United States	Virginia Endocrinology Research SC-2	Chesapeake	Virginia
United States	Great Falls Clinic	Great Falls	Montana
United States	Baylor College of Medicine Ben Taub General Hosp.	Houston	Texas
United States	East Coast Institute for Research East Coast Inst. for Res(ECIR)	Jacksonville	Florida
United States	Diabetes and Endocrine Associates La Mesa Location	Multiple Locations	California
United States	Vanderbilt Clinical Trials Center SOM230B2219	Nashville	Tennessee
United States	Robert Wood Johnson Medical School - Rutgers SC	New Brunswick	New Jersey
United States	Columbia University Medical Center New York Presbyterian Neuroendocrine Unit	New York	New York
United States	Lenox Hill Hospital/Manhattan Eye, Ear and Throat Hospital SC	New York	New York
United States	The Mount Sinai Hospital SC	New York	New York
United States	Allegheny Endocrinology Associates SC	Pittsburgh	Pennsylvania
United States	Washington University SC - SOM230B2411	Saint Louis	Missouri
United States	Swedish Medical Center Dept.ofSeattle Neuroscience(2)	Seattle	Washington
United States	LA Biomedical Research at Harbor UCLA Medical Center SC - SOM230B2219	Torrance	California
United States	Coastal Metabolic Research Centre SC	Ventura	California

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Belgium,  Brazil,  China,  Denmark,  Germany,  India,  Peru,  Poland,  Russian Federation,  Thailand,  Turkey, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in HbA1c From Randomization to Approximately 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.	Randomization, 16 weeks
Secondary	Change in HbA1c From Randomization (R) Over Time Per Randomized Arm	Absolute change in HbA1c overtime from randomization (i.e. start of randomized antidiabetic treatment) to end of core phase 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)
Secondary	Change in FPG (Fasting Plasma Glucose) From Randomization Until 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	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
Secondary	Percentage of Participants in the Incretin-based Arm Who Required Anti-diabetic Rescue Therapy With Insulin	The percentage of participants who received anti-diabetic rescue therapy in incretin based therapy is summarized.	Randomization to up to 16 weeks
Secondary	Absolute Change in HbA1c From Baseline to 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	Baseline, up to 32 weeks (end of Core phase)
Secondary	Absolute Change in FPG From Baseline to 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.	Baseline, Up to 32 weeks (end of Core Phase)
Secondary	Percentage of Participants With = 0.3% HbA1c Increase to End of Core Phase	Percentage of participants with = 0.3% HbA1c increase in the incretin based therapy arm and the insulin arm.	Randomization, up to 16 weeks