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

Browse trials for

• Pituitary ACTH Hypersecretion 64
• Acromegaly 202
• Hyperglycemia 800

Keywords

• Cushing's disease
• acromegaly
• pasireotide
• hyperglycemia

Pituitary ACTH Hypersecretion

64 studies on the registry are indexed under Pituitary ACTH Hypersecretion; 16 are open to participants now.

This study's enrollment of 249 is above the median of 44 across 40 interventional studies indexed under Pituitary ACTH Hypersecretion.

Lead sponsor

Novartis Pharmaceuticals is the lead sponsor of 2,718 studies on the registry; 221 are open to participants now.

Of its 585 completed or terminated interventional studies of FDA-regulated products, 438 (75%) have results posted.

Study arms

• 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. · Drug: Sitagliptin · Drug: Liraglutide · Drug: Insulin · Drug: Pasireotide LAR · Drug: 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. · Drug: Insulin · Drug: Pasireotide LAR · Drug: Metformin

• Other
  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. · Drug: Insulin · Drug: Pasireotide LAR · Drug: Metformin

Interventions

• DrugPasireotide s.c.

  Administered to Cushing's disease participants.

  Also known as: SOM230

• DrugSitagliptin

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

• DrugLiraglutide

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

• DrugInsulin

  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.

• DrugPasireotide LAR

  Administered to Acromegaly participants.

  Also known as: SOM230

• DrugMetformin

  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 outcomes

1. 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.

   Time frame: Randomization, 16 weeks

Secondary outcomes

1. 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

   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)

2. 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

   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

3. 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.

   Time frame: Randomization to up to 16 weeks

4. 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

   Time frame: Baseline, up to 32 weeks (end of Core phase)

5. 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.

   Time frame: Baseline, Up to 32 weeks (end of Core Phase)

6. 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.

   Time frame: Randomization, up to 16 weeks

Baseline characteristics

Publications

• 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. PubMed 34275099 ↗
• 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. PubMed 27405306 ↗

Study documents

• Study protocol ↗ · Mar 17, 2017
• Statistical analysis plan ↗ · Jun 25, 2018

PDFs hosted by the registry, ClinicalTrials.gov.

Individual participant data

Plan to share: Yes — 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