Study of Management of Pasireotide-induced Hyperglycemia in Adult Patients With Cushing's Disease or Acromegaly
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| ClinicalTrials.gov Identifier: NCT02060383 |
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Recruitment Status :
Completed
First Posted : February 12, 2014
Results First Posted : May 29, 2019
Last Update Posted : May 29, 2019
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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 |
| 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 |
|---|---|
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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.
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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. |
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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.
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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. |
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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:
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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. |
- 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.
- 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
- 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
- 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.
- 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
- 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.
- 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.
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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.
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
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| Study Director: | Novartis Pharmaceuticals | Novartis Pharmaceuticals |
Documents provided by Novartis ( Novartis Pharmaceuticals ):
| Responsible Party: | Novartis Pharmaceuticals |
| ClinicalTrials.gov Identifier: | NCT02060383 |
| 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 |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
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Cushing's disease acromegaly pasireotide hyperglycemia |
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ACTH-Secreting Pituitary Adenoma 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 Metformin Sitagliptin Phosphate Liraglutide Pasireotide Somatostatin Hypoglycemic Agents Physiological Effects of Drugs |