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

Primary Purpose

Cushing's Disease, Acromegaly

Status
Completed
Phase
Phase 4
Locations
International
Study Type
Interventional
Intervention
Pasireotide s.c.
Sitagliptin
Liraglutide
Insulin
Pasireotide LAR
Metformin
Sponsored by
Novartis Pharmaceuticals
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional supportive care trial for Cushing's Disease focused on measuring Cushing's disease, acromegaly, pasireotide, hyperglycemia

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept 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.

Sites / Locations

  • Diabetes and Endocrine Associates La Mesa Location
  • LA Biomedical Research at Harbor UCLA Medical Center SC - SOM230B2219
  • Coastal Metabolic Research Centre SC
  • East Coast Institute for Research East Coast Inst. for Res(ECIR)
  • Washington University SC - SOM230B2411
  • Great Falls Clinic
  • Robert Wood Johnson Medical School - Rutgers SC
  • The Mount Sinai Hospital SC
  • Columbia University Medical Center New York Presbyterian Neuroendocrine Unit
  • Lenox Hill Hospital/Manhattan Eye, Ear and Throat Hospital SC
  • Allegheny Endocrinology Associates SC
  • Vanderbilt Clinical Trials Center SOM230B2219
  • Baylor College of Medicine Ben Taub General Hosp.
  • Virginia Endocrinology Research SC-2
  • Swedish Medical Center Dept.ofSeattle Neuroscience(2)
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Other

Arm Label

Incretin based therapy (randomized group)

Insulin (randomized group)

Non-Randomized Arm

Arm 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.

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.

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

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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
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
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.
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
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.
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.

Full Information

First Posted
February 10, 2014
Last Updated
May 7, 2019
Sponsor
Novartis Pharmaceuticals
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1. Study Identification

Unique Protocol Identification Number
NCT02060383
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
Study Type
Interventional

2. Study Status

Record Verification Date
May 2019
Overall Recruitment Status
Completed
Study Start Date
May 23, 2014 (Actual)
Primary Completion Date
February 5, 2018 (Actual)
Study Completion Date
March 26, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novartis Pharmaceuticals

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cushing's Disease, Acromegaly
Keywords
Cushing's disease, acromegaly, pasireotide, hyperglycemia

7. Study Design

Primary Purpose
Supportive Care
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
249 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Incretin based therapy (randomized group)
Arm Type
Experimental
Arm 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.
Arm Title
Insulin (randomized group)
Arm Type
Experimental
Arm 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.
Arm Title
Non-Randomized Arm
Arm Type
Other
Arm 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
Intervention Type
Drug
Intervention Name(s)
Pasireotide s.c.
Other Intervention Name(s)
SOM230
Intervention Description
Administered to Cushing's disease participants.
Intervention Type
Drug
Intervention Name(s)
Sitagliptin
Intervention Description
Taken for approximately 16 weeks during the core study phase or until the drug was found not to be effective
Intervention Type
Drug
Intervention Name(s)
Liraglutide
Intervention Description
Participant switched to liraglutide if sitagliptin was found not to be effective.
Intervention Type
Drug
Intervention Name(s)
Insulin
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Pasireotide LAR
Other Intervention Name(s)
SOM230
Intervention Description
Administered to Acromegaly participants.
Intervention Type
Drug
Intervention Name(s)
Metformin
Intervention Description
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.
Primary Outcome Measure Information:
Title
Change in HbA1c From Randomization to Approximately 16 Weeks
Description
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.
Time Frame
Randomization, 16 weeks
Secondary Outcome Measure Information:
Title
Change in HbA1c From Randomization (R) Over Time Per Randomized Arm
Description
Absolute change in HbA1c overtime from randomization (i.e. start of randomized antidiabetic treatment) to end of core phase per randomized arm
Time Frame
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)
Title
Change in FPG (Fasting Plasma Glucose) From Randomization Until End of Core Phase
Description
Absolute change in fasting glucose overtime from randomization (i.e. start of randomized antidiabetic treatment) to end of core phase 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, end of Core phase
Title
Percentage of Participants in the Incretin-based Arm Who Required Anti-diabetic Rescue Therapy With Insulin
Description
The percentage of participants who received anti-diabetic rescue therapy in incretin based therapy is summarized.
Time Frame
Randomization to up to 16 weeks
Title
Absolute Change in HbA1c From Baseline to End of Core Phase
Description
Absolute change in HbA1c from baseline to end of core phase in the incretin based therapy arm and the insulin arm
Time Frame
Baseline, up to 32 weeks (end of Core phase)
Title
Absolute Change in FPG From Baseline to End of Core Phase
Description
Absolute change in FPG from baseline to end of core phase in the incretin based therapy arm and the insulin arm.
Time Frame
Baseline, Up to 32 weeks (end of Core Phase)
Title
Percentage of Participants With ≤ 0.3% HbA1c Increase to End of Core Phase
Description
Percentage of participants with ≤ 0.3% HbA1c increase in the incretin based therapy arm and the insulin arm.
Time Frame
Randomization, up to 16 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Novartis Pharmaceuticals
Organizational Affiliation
Novartis Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
Diabetes and Endocrine Associates La Mesa Location
City
Multiple Locations
State/Province
California
Country
United States
Facility Name
LA Biomedical Research at Harbor UCLA Medical Center SC - SOM230B2219
City
Torrance
State/Province
California
ZIP/Postal Code
90502
Country
United States
Facility Name
Coastal Metabolic Research Centre SC
City
Ventura
State/Province
California
ZIP/Postal Code
93003
Country
United States
Facility Name
East Coast Institute for Research East Coast Inst. for Res(ECIR)
City
Jacksonville
State/Province
Florida
ZIP/Postal Code
32223
Country
United States
Facility Name
Washington University SC - SOM230B2411
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
Great Falls Clinic
City
Great Falls
State/Province
Montana
ZIP/Postal Code
59405
Country
United States
Facility Name
Robert Wood Johnson Medical School - Rutgers SC
City
New Brunswick
State/Province
New Jersey
ZIP/Postal Code
08901
Country
United States
Facility Name
The Mount Sinai Hospital SC
City
New York
State/Province
New York
ZIP/Postal Code
10029
Country
United States
Facility Name
Columbia University Medical Center New York Presbyterian Neuroendocrine Unit
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
Facility Name
Lenox Hill Hospital/Manhattan Eye, Ear and Throat Hospital SC
City
New York
State/Province
New York
ZIP/Postal Code
10075
Country
United States
Facility Name
Allegheny Endocrinology Associates SC
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15212
Country
United States
Facility Name
Vanderbilt Clinical Trials Center SOM230B2219
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37212-8210
Country
United States
Facility Name
Baylor College of Medicine Ben Taub General Hosp.
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Virginia Endocrinology Research SC-2
City
Chesapeake
State/Province
Virginia
ZIP/Postal Code
23321
Country
United States
Facility Name
Swedish Medical Center Dept.ofSeattle Neuroscience(2)
City
Seattle
State/Province
Washington
ZIP/Postal Code
98122-4379
Country
United States
Facility Name
Novartis Investigative Site
City
Leuven
ZIP/Postal Code
3000
Country
Belgium
Facility Name
Novartis Investigative Site
City
Wilrijk
ZIP/Postal Code
2610
Country
Belgium
Facility Name
Novartis Investigative Site
City
Rio de Janeiro
State/Province
RJ
ZIP/Postal Code
21941-590
Country
Brazil
Facility Name
Novartis Investigative Site
City
Porto Alegre
State/Province
RS
ZIP/Postal Code
90560-030
Country
Brazil
Facility Name
Novartis Investigative Site
City
Joinville
State/Province
SC
ZIP/Postal Code
89201260
Country
Brazil
Facility Name
Novartis Investigative Site
City
São Paulo
State/Province
SP
ZIP/Postal Code
05403 000
Country
Brazil
Facility Name
Novartis Investigative Site
City
Beijing
State/Province
Beijing
ZIP/Postal Code
100730
Country
China
Facility Name
Novartis Investigative Site
City
Guangzhou
State/Province
Guangdong
ZIP/Postal Code
510000
Country
China
Facility Name
Novartis Investigative Site
City
Chengdu
State/Province
Sichuan
ZIP/Postal Code
610041
Country
China
Facility Name
Novartis Investigative Site
City
Aalborg
ZIP/Postal Code
9000
Country
Denmark
Facility Name
Novartis Investigative Site
City
Aarhus
ZIP/Postal Code
DK-8000
Country
Denmark
Facility Name
Novartis Investigative Site
City
Herlev
ZIP/Postal Code
DK-2730
Country
Denmark
Facility Name
Novartis Investigative Site
City
Odense C
ZIP/Postal Code
DK-5000
Country
Denmark
Facility Name
Novartis Investigative Site
City
Erlangen
ZIP/Postal Code
91054
Country
Germany
Facility Name
Novartis Investigative Site
City
Freiburg
ZIP/Postal Code
79106
Country
Germany
Facility Name
Novartis Investigative Site
City
Oldenburg
ZIP/Postal Code
26122
Country
Germany
Facility Name
Novartis Investigative Site
City
Bangalore
State/Province
Karnataka
ZIP/Postal Code
560054
Country
India
Facility Name
Novartis Investigative Site
City
Vellore
State/Province
Tamil Nadu
ZIP/Postal Code
632004
Country
India
Facility Name
Novartis Investigative Site
City
San Isidro
State/Province
Lima
ZIP/Postal Code
27
Country
Peru
Facility Name
Novartis Investigative Site
City
Warszawa
ZIP/Postal Code
00-909
Country
Poland
Facility Name
Novartis Investigative Site
City
Wroclaw
ZIP/Postal Code
50 367
Country
Poland
Facility Name
Novartis Investigative Site
City
Saint Petersburg
ZIP/Postal Code
197341
Country
Russian Federation
Facility Name
Novartis Investigative Site
City
Bangkok
ZIP/Postal Code
10400
Country
Thailand
Facility Name
Novartis Investigative Site
City
Bangkok
ZIP/Postal Code
10700
Country
Thailand
Facility Name
Novartis Investigative Site
City
Songkla
ZIP/Postal Code
90110
Country
Thailand
Facility Name
Novartis Investigative Site
City
Altunizade
ZIP/Postal Code
34662
Country
Turkey
Facility Name
Novartis Investigative Site
City
Ankara
ZIP/Postal Code
06500
Country
Turkey
Facility Name
Novartis Investigative Site
City
Antalya
ZIP/Postal Code
07070
Country
Turkey

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com
Citations:
PubMed Identifier
34275099
Citation
Samson SL, Gu F, Feldt-Rasmussen U, Zhang S, Yu Y, Witek P, Kalra P, Pedroncelli AM, Pultar P, Jabbour N, Paul M, Bolanowski M. Managing pasireotide-associated hyperglycemia: a randomized, open-label, Phase IV study. Pituitary. 2021 Dec;24(6):887-903. doi: 10.1007/s11102-021-01161-4. Epub 2021 Jul 18.
Results Reference
derived
PubMed Identifier
27405306
Citation
Silverstein JM. Hyperglycemia induced by pasireotide in patients with Cushing's disease or acromegaly. Pituitary. 2016 Oct;19(5):536-43. doi: 10.1007/s11102-016-0734-1.
Results Reference
derived

Learn more about this trial

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

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