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

NCT ID: NCT02060383

Last Updated: 2019-05-29

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

View full results

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

COMPLETED

Clinical Phase

PHASE4

Total Enrollment

249 participants

Study Classification

INTERVENTIONAL

Study Start Date

2014-05-23

Study Completion Date

2018-03-26

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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.

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Cushing's Disease Acromegaly

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

SUPPORTIVE_CARE

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Incretin based therapy (randomized group)

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.

Group Type EXPERIMENTAL

Pasireotide s.c.

Intervention Type DRUG

Administered to Cushing's disease participants.

Sitagliptin

Intervention Type DRUG

Taken for approximately 16 weeks during the core study phase or until the drug was found not to be effective

Liraglutide

Intervention Type DRUG

Participant switched to liraglutide if sitagliptin was found not to be effective.

Insulin

Intervention Type DRUG

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

Intervention Type DRUG

Administered to Acromegaly participants.

Metformin

Intervention Type DRUG

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.

Insulin (randomized group)

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.

Group Type EXPERIMENTAL

Pasireotide s.c.

Intervention Type DRUG

Administered to Cushing's disease participants.

Insulin

Intervention Type DRUG

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

Intervention Type DRUG

Administered to Acromegaly participants.

Metformin

Intervention Type DRUG

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.

Non-Randomized Arm

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

Group Type OTHER

Pasireotide s.c.

Intervention Type DRUG

Administered to Cushing's disease participants.

Insulin

Intervention Type DRUG

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

Intervention Type DRUG

Administered to Acromegaly participants.

Metformin

Intervention Type DRUG

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.

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Pasireotide s.c.

Administered to Cushing's disease participants.

Intervention Type DRUG

Sitagliptin

Taken for approximately 16 weeks during the core study phase or until the drug was found not to be effective

Intervention Type DRUG

Liraglutide

Participant switched to liraglutide if sitagliptin was found not to be effective.

Intervention Type DRUG

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.

Intervention Type DRUG

Pasireotide LAR

Administered to Acromegaly participants.

Intervention Type DRUG

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.

Intervention Type DRUG

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

SOM230 SOM230

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

Novartis Pharmaceuticals

INDUSTRY

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Responsibility Role SPONSOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Novartis Pharmaceuticals

Role: STUDY_DIRECTOR

Novartis Pharmaceuticals

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Diabetes and Endocrine Associates La Mesa Location

Multiple Locations, California, United States

Site Status

LA Biomedical Research at Harbor UCLA Medical Center SC - SOM230B2219

Torrance, California, United States

Site Status

Coastal Metabolic Research Centre SC

Ventura, California, United States

Site Status

East Coast Institute for Research East Coast Inst. for Res(ECIR)

Jacksonville, Florida, United States

Site Status

Washington University SC - SOM230B2411

St Louis, Missouri, United States

Site Status

Great Falls Clinic

Great Falls, Montana, United States

Site Status

Robert Wood Johnson Medical School - Rutgers SC

New Brunswick, New Jersey, United States

Site Status

The Mount Sinai Hospital SC

New York, New York, United States

Site Status

Columbia University Medical Center New York Presbyterian Neuroendocrine Unit

New York, New York, United States

Site Status

Lenox Hill Hospital/Manhattan Eye, Ear and Throat Hospital SC

New York, New York, United States

Site Status

Allegheny Endocrinology Associates SC

Pittsburgh, Pennsylvania, United States

Site Status

Vanderbilt Clinical Trials Center SOM230B2219

Nashville, Tennessee, United States

Site Status

Baylor College of Medicine Ben Taub General Hosp.

Houston, Texas, United States

Site Status

Virginia Endocrinology Research SC-2

Chesapeake, Virginia, United States

Site Status

Swedish Medical Center Dept.ofSeattle Neuroscience(2)

Seattle, Washington, United States

Site Status

Novartis Investigative Site

Leuven, , Belgium

Site Status

Novartis Investigative Site

Wilrijk, , Belgium

Site Status

Novartis Investigative Site

Rio de Janeiro, Rio de Janeiro, Brazil

Site Status

Novartis Investigative Site

Porto Alegre, Rio Grande do Sul, Brazil

Site Status

Novartis Investigative Site

Joinville, Santa Catarina, Brazil

Site Status

Novartis Investigative Site

São Paulo, São Paulo, Brazil

Site Status

Novartis Investigative Site

Beijing, Beijing Municipality, China

Site Status

Novartis Investigative Site

Guangzhou, Guangdong, China

Site Status

Novartis Investigative Site

Chengdu, Sichuan, China

Site Status

Novartis Investigative Site

Aalborg, , Denmark

Site Status

Novartis Investigative Site

Aarhus, , Denmark

Site Status

Novartis Investigative Site

Herlev, , Denmark

Site Status

Novartis Investigative Site

Odense C, , Denmark

Site Status

Novartis Investigative Site

Erlangen, , Germany

Site Status

Novartis Investigative Site

Freiburg im Breisgau, , Germany

Site Status

Novartis Investigative Site

Oldenburg, , Germany

Site Status

Novartis Investigative Site

Bangalore, Karnataka, India

Site Status

Novartis Investigative Site

Vellore, Tamil Nadu, India

Site Status

Novartis Investigative Site

San Isidro, Lima region, Peru

Site Status

Novartis Investigative Site

Warsaw, , Poland

Site Status

Novartis Investigative Site

Wroclaw, , Poland

Site Status

Novartis Investigative Site

Saint Petersburg, , Russia

Site Status

Novartis Investigative Site

Bangkok, , Thailand

Site Status

Novartis Investigative Site

Bangkok, , Thailand

Site Status

Novartis Investigative Site

Songkhla, , Thailand

Site Status

Novartis Investigative Site

Altunizade, , Turkey (Türkiye)

Site Status

Novartis Investigative Site

Ankara, , Turkey (Türkiye)

Site Status

Novartis Investigative Site

Antalya, , Turkey (Türkiye)

Site Status

Countries

Review the countries where the study has at least one active or historical site.

United States Belgium Brazil China Denmark Germany India Peru Poland Russia Thailand Turkey (Türkiye)

References

Explore related publications, articles, or registry entries linked to this study.

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.

Reference Type DERIVED
PMID: 34275099 (View on PubMed)

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.

Reference Type DERIVED
PMID: 27405306 (View on PubMed)

Provided Documents

Download supplemental materials such as informed consent forms, study protocols, or participant manuals.

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

2012-002916-16

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CSOM230B2219

Identifier Type: -

Identifier Source: org_study_id

More Related Trials

Additional clinical trials that may be relevant based on similarity analysis.

Liraglutide in Type 1 Diabetes
NCT01612468 COMPLETED PHASE4
The Lira Pump Trial
NCT02351232 COMPLETED PHASE2/PHASE3