Clinical trial NCT02060383: 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
Overall status: COMPLETED
Phase: PHASE4
Conditions: Cushing's Disease
Acromegaly
Keywords: Cushing's disease
acromegaly
pasireotide
hyperglycemia
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2014-02-12
Enrollment: 249
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

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.


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.

Primary outcomes:
measure: Change in HbA1c From Randomization to Approximately 16 Weeks
timeFrame: Randomization, 16 weeks
Secondary outcomes:
measure: Change in HbA1c From Randomization (R) Over Time Per Randomized Arm
timeFrame: 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)
measure: Change in FPG (Fasting Plasma Glucose) From Randomization Until End of Core Phase
timeFrame: 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
measure: Percentage of Participants in the Incretin-based Arm Who Required Anti-diabetic Rescue Therapy With Insulin
timeFrame: Randomization to up to 16 weeks
measure: Absolute Change in HbA1c From Baseline to End of Core Phase
timeFrame: Baseline, up to 32 weeks (end of Core phase)
measure: Absolute Change in FPG From Baseline to End of Core Phase
timeFrame: Baseline, Up to 32 weeks (end of Core Phase)
measure: Percentage of Participants With ≤ 0.3% HbA1c Increase to End of Core Phase
timeFrame: Randomization, up to 16 weeks
Other outcomes:
Locations:
city: Multiple Locations
country: United States
facility: Diabetes and Endocrine Associates La Mesa Location
state: California
city: Torrance
country: United States
facility: LA Biomedical Research at Harbor UCLA Medical Center SC - SOM230B2219
state: California
city: Ventura
country: United States
facility: Coastal Metabolic Research Centre SC
state: California
city: Jacksonville
country: United States
facility: East Coast Institute for Research East Coast Inst. for Res(ECIR)
state: Florida
city: Saint Louis
country: United States
facility: Washington University SC - SOM230B2411
state: Missouri
city: Great Falls
country: United States
facility: Great Falls Clinic
state: Montana
city: New Brunswick
country: United States
facility: Robert Wood Johnson Medical School - Rutgers SC
state: New Jersey
city: New York
country: United States
facility: The Mount Sinai Hospital SC
state: New York
city: New York
country: United States
facility: Columbia University Medical Center New York Presbyterian Neuroendocrine Unit
state: New York
city: New York
country: United States
facility: Lenox Hill Hospital/Manhattan Eye, Ear and Throat Hospital SC
state: New York
city: Pittsburgh
country: United States
facility: Allegheny Endocrinology Associates SC
state: Pennsylvania
city: Nashville
country: United States
facility: Vanderbilt Clinical Trials Center SOM230B2219
state: Tennessee
city: Houston
country: United States
facility: Baylor College of Medicine Ben Taub General Hosp.
state: Texas
city: Chesapeake
country: United States
facility: Virginia Endocrinology Research SC-2
state: Virginia
city: Seattle
country: United States
facility: Swedish Medical Center Dept.ofSeattle Neuroscience(2)
state: Washington
city: Leuven
country: Belgium
facility: Novartis Investigative Site
city: Wilrijk
country: Belgium
facility: Novartis Investigative Site
city: Rio de Janeiro
country: Brazil
facility: Novartis Investigative Site
state: RJ
city: Porto Alegre
country: Brazil
facility: Novartis Investigative Site
state: RS
city: Joinville
country: Brazil
facility: Novartis Investigative Site
state: SC
city: São Paulo
country: Brazil
facility: Novartis Investigative Site
state: SP
city: Beijing
country: China
facility: Novartis Investigative Site
state: Beijing
city: Guangzhou
country: China
facility: Novartis Investigative Site
state: Guangdong
city: Chengdu
country: China
facility: Novartis Investigative Site
state: Sichuan
city: Aalborg
country: Denmark
facility: Novartis Investigative Site
city: Aarhus
country: Denmark
facility: Novartis Investigative Site
city: Herlev
country: Denmark
facility: Novartis Investigative Site
city: Odense C
country: Denmark
facility: Novartis Investigative Site
city: Erlangen
country: Germany
facility: Novartis Investigative Site
city: Freiburg
country: Germany
facility: Novartis Investigative Site
city: Oldenburg
country: Germany
facility: Novartis Investigative Site
city: Bangalore
country: India
facility: Novartis Investigative Site
state: Karnataka
city: Vellore
country: India
facility: Novartis Investigative Site
state: Tamil Nadu
city: San Isidro
country: Peru
facility: Novartis Investigative Site
state: Lima
city: Warszawa
country: Poland
facility: Novartis Investigative Site
city: Wroclaw
country: Poland
facility: Novartis Investigative Site
city: Saint Petersburg
country: Russian Federation
facility: Novartis Investigative Site
city: Bangkok
country: Thailand
facility: Novartis Investigative Site
city: Bangkok
country: Thailand
facility: Novartis Investigative Site
city: Songkla
country: Thailand
facility: Novartis Investigative Site
city: Altunizade
country: Turkey
facility: Novartis Investigative Site
city: Ankara
country: Turkey
facility: Novartis Investigative Site
city: Antalya
country: Turkey
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References:
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.
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.