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

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ClinicalTrials.gov Identifier: NCT02060383
Recruitment Status : Completed
First Posted : February 12, 2014
Results First Posted : May 29, 2019
Last Update Posted : May 29, 2019
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

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.


Condition or disease Intervention/treatment Phase
Cushing's Disease Acromegaly Drug: Pasireotide s.c. Drug: Sitagliptin Drug: Liraglutide Drug: Insulin Drug: Pasireotide LAR Drug: Metformin Phase 4

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 249 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (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
Actual Study Start Date : May 23, 2014
Actual Primary Completion Date : February 5, 2018
Actual Study Completion Date : March 26, 2018


Arm Intervention/treatment
Experimental: 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.
Drug: Pasireotide s.c.
Administered to Cushing's disease participants.
Other Name: SOM230

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

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

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.


Drug: Pasireotide LAR
Administered to Acromegaly participants.
Other Name: SOM230

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.


Experimental: 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.
Drug: Pasireotide s.c.
Administered to Cushing's disease participants.
Other Name: SOM230

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.


Drug: Pasireotide LAR
Administered to Acromegaly participants.
Other Name: SOM230

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.


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
Drug: Pasireotide s.c.
Administered to Cushing's disease participants.
Other Name: SOM230

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.


Drug: Pasireotide LAR
Administered to Acromegaly participants.
Other Name: SOM230

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.





Primary Outcome Measures :
  1. Change in HbA1c From Randomization to Approximately 16 Weeks [ Time Frame: Randomization, 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 :
  1. Change in HbA1c From Randomization (R) Over Time 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) ]
    Absolute change in HbA1c overtime from randomization (i.e. start of randomized antidiabetic treatment) to end of core phase per randomized arm

  2. Change in FPG (Fasting Plasma Glucose) From Randomization Until End of Core Phase [ 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 ]
    Absolute change in fasting glucose overtime from randomization (i.e. start of randomized antidiabetic treatment) to end of core phase per randomized arm

  3. Percentage of Participants in the Incretin-based Arm Who Required Anti-diabetic Rescue Therapy With Insulin [ Time Frame: Randomization to up to 16 weeks ]
    The percentage of participants who received anti-diabetic rescue therapy in incretin based therapy is summarized.

  4. Absolute Change in HbA1c From Baseline to End of Core Phase [ Time Frame: Baseline, up to 32 weeks (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

  5. Absolute Change in FPG From Baseline to End of Core Phase [ Time Frame: Baseline, Up to 32 weeks (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.

  6. Percentage of Participants With ≤ 0.3% HbA1c Increase to End of Core Phase [ Time Frame: Randomization, up to 16 weeks ]
    Percentage of participants with ≤ 0.3% HbA1c increase in the incretin based therapy arm and the insulin arm.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02060383


  Show 43 Study Locations
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
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Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  Study Documents (Full-Text)

Documents provided by Novartis ( Novartis Pharmaceuticals ):
Study Protocol  [PDF] March 17, 2017
Statistical Analysis Plan  [PDF] June 25, 2018


Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT02060383     History of Changes
Other Study ID Numbers: CSOM230B2219
2012-002916-16 ( EudraCT Number )
First Posted: February 12, 2014    Key Record Dates
Results First Posted: May 29, 2019
Last Update Posted: May 29, 2019
Last Verified: May 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
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


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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Novartis ( Novartis Pharmaceuticals ):
Cushing's disease
acromegaly
pasireotide
hyperglycemia
Additional relevant MeSH terms:
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ACTH-Secreting Pituitary Adenoma
Protease Inhibitors
Acromegaly
Pituitary ACTH Hypersecretion
Hyperglycemia
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
Adenoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Pituitary Neoplasms
Endocrine Gland Neoplasms
Neoplasms by Site
Insulin
Insulin, Globin Zinc
Metformin
Sitagliptin Phosphate
Liraglutide
Incretins