Clinical trial NCT00600886: Safety and Efficacy of Pasireotide Long Acting Release (LAR) vs. Octreotide LAR in Patients With Active Acromegaly
Official title: A Multicenter, Randomized, Blinded Study to Assess Safety and Efficacy of Pasireotide LAR vs. Octreotide LAR in Patients With Active Acromegaly
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Acromegaly
Keywords: Acromegaly,
adult,
growth hormone,
insulin-like growth factor I,
somatostatin analogue
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2008-01-25
Enrollment: 358
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The patients received either Pasireotide LAR or Octreotide LAR for one year of treatment.

The objective of this study was to compare the proportion of patients with a reduction of mean GH level to \<2.5 µg/L and the normalization of IGF-1 to within normal limits (age and sex related) between the two treatment groups (pasireotide LAR and octreotide LAR) at 12 months.

Following one year of treatment patients could proceed into the study extension.

Patients who did not respond to the treatment they were randomized to (based on month 12 assessment results) were switched to the other treatment arm at month 13.


Eligibility criteria: Inclusion criteria:

* Patients with active acromegaly (based on elevated GH and IGF-1 levels)
* Patients who have undergone one or more pituitary surgeries, but have not been treated medically, or de-novo patients presenting a visible pituitary adenoma on MRI and who refuse pituitary surgery or for whom pituitary surgery is contraindicated
* Patients for whom written informed consent to participate in the study has been obtained prior to any study related activity

Exclusion criteria:

* Patients who are being or were treated with octreotide, lanreotide, dopamine agonists or GH antagonists with the exception of a single dose of short-acting octrotide or short-acting dopamine agonists. In case of a single dose of short-acting octrotide, the dose should not be used to predict the response to the octretide treatment. The single dose of short-acting octreotide or short-acting dopamine agonists should not be administered in the 3 days prior to randomization
* Patients with compression of the optic chiasm causing any visual field defect
* Patients who have received pituitary irradiation within the last ten years prior to visit 1
* Poorly controlled diabetic patients

Other protocol-defined inclusion/exclusion criteria may apply

Primary outcomes:
measure: Percentage of Participants With a Reduction of Mean GH Level to <2.5 μg/L and the Normalization of IGF-1
timeFrame: 12 months
Secondary outcomes:
measure: Percentage of Participants With a Reduction of Mean GH Level to < 2.5μg/L
timeFrame: 12 Months
measure: Change From Baseline in Tumor Volume at 12 Months
timeFrame: Baseline, 12 Months
measure: Percentage of Participants With Normalization of IGF-1
timeFrame: 12 Months
measure: Percentage of Participants With a Reduction of Mean GH Level to < 2.5μg/L and Normalization of IGF-1
timeFrame: Months 3, 6, 9, 12, 16, 19, 22, 25
measure: Summary of Mean GH Values
timeFrame: Baseline, Months 3, 6, 9, 12, 16, 19, 22, 25
measure: Time to First Response for Patients Achieving a Reduction of Mean GH Level to < 2.5 μg/L and Normalization of IGF-1 (No. of Responders: Pasireotite LAR = 81, Octreotide LAR = 63) )
timeFrame: Up to 26 months
measure: Severity Scores of Acromegaly Symptoms
timeFrame: Baseline, Months 12, 25
measure: Ring Size
timeFrame: Baseline, Months 12, 25
measure: Health-related Quality-of-life as Measured by the AcroQoL Questionnaire
timeFrame: Baseline, Months 12, 25
measure: Summary of Prolactin Levels
timeFrame: Baseline, Months 12, 25
measure: Duration of Response for Patients Achieving a Reduction of Mean GH Level to <2.5 μg/L and the Normalization of IGF-1 at Month 12 (No. of Responders: Pasireotide LAR = 51, Octreotide LAR = 32)
timeFrame: Up to 26 months
measure: Pasireotide Trough Concentrations by Incident Dose
timeFrame: Months 1 - 12
measure: Octreotide Trough Concentrations by Incident Dose
timeFrame: Months 1 - 12
measure: Percentage of Participants With a Reduction of Mean GH Level to < 2.5μg/L and Normalization of IGF-1 After Crossover
timeFrame: Months 3, 6, 9, 12 after crossover
measure: Percentage of Participants With a Reduction of Mean GH Level to < 2.5μg/L
timeFrame: Months 3, 6, 9, 12, 16, 19, 22, 25
measure: Percentage of Participants With Normalization of IGF-1
timeFrame: Months 3, 6, 9, 12, 16, 19, 22, 25
measure: Change From Baseline in Tumor Volume
timeFrame: Baseline, months 6, 12, 19, 25
measure: Percentage of Participants With a Reduction of Mean GH Level to < 2.5μg/L After Crossover
timeFrame: Months 3, 6, 9, 12 after crossover
measure: Percentage of Participants With Normalization of IGF-1 After Crossover
timeFrame: Months 3, 6, 9, 12 after crossover
measure: Summary of Mean GH Values After Crossover
timeFrame: Extension baseline, months 3, 6, 9, 12 after crossover
measure: Change From Extension Baseline in Tumor Volume After Crossover
timeFrame: Extension baseline, months 6, 12 after crossover
measure: Severity Scores of Acromegaly Symptoms After Crossover
timeFrame: Extension baseline, month 12 after crossover
measure: Ring Size After Crossover
timeFrame: Extension baseline, month 12 after crossover
measure: Health-related Quality-of-life as Measured by the AcroQoL Questionnaire After Crossover
timeFrame: Extension baseline, months 12 after crossover
measure: Summary of Prolactin Levels After Crossover
timeFrame: Extension baseline, month 12 after crossover
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Cedars Sinai Medical Center The Pituitary Center
state: California
city: Los Angeles
country: United States
facility: University of California at Los Angeles Division of Endocrinology
state: California
city: Stanford
country: United States
facility: Stanford University Medical Center Stanford Cancer Center (3)
state: California
city: Gainesville
country: United States
facility: University of Florida SC
state: Florida
city: Baltimore
country: United States
facility: Johns Hopkins University School of Medicine Dept.ofJohnsHopkinsUniv.
state: Maryland
city: Ann Arbor
country: United States
facility: University of Michigan Comprehensive Cancer Center Deptof Endocrinology&Diabetes
state: Michigan
city: New York
country: United States
facility: Columbia University Medical Center- New York Presbyterian Dept. of CU Collegeof Phys&Sur
state: New York
city: Northport
country: United States
facility: Northport VA Medical Center CSOM230C2305
state: New York
city: Portland
country: United States
facility: Oregon Health & Sciences University DeptofOregonHealth&Sciences(3)
state: Oregon
city: Pittsburgh
country: United States
facility: Allegheny Endocrinology Associates
state: Pennsylvania
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center Danziger Research Bldg.
state: Texas
city: Houston
country: United States
facility: University of Texas/MD Anderson Cancer Center Regulatory -12
state: Texas
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: Seattle
country: United States
facility: Swedish Medical Center Dept.ofSeattle Neuroscience(2)
state: Washington
city: Caba
country: Argentina
facility: Novartis Investigative Site
state: Buenos Aires
city: Capital Federal
country: Argentina
facility: Novartis Investigative Site
state: Buenos Aires
city: Buenos Aires
country: Argentina
facility: Novartis Investigative Site
city: Brussel
country: Belgium
facility: Novartis Investigative Site
city: Bruxelles
country: Belgium
facility: Novartis Investigative Site
city: Gent
country: Belgium
facility: Novartis Investigative Site
city: Leuven
country: Belgium
facility: Novartis Investigative Site
city: Fortaleza
country: Brazil
facility: Novartis Investigative Site
state: CE
city: Brasilia
country: Brazil
facility: Novartis Investigative Site
state: DF
city: Sao Luis
country: Brazil
facility: Novartis Investigative Site
state: MA
city: Curitiba
country: Brazil
facility: Novartis Investigative Site
state: PR
city: Rio de Janeiro
country: Brazil
facility: Novartis Investigative Site
state: RJ
city: Sao Paulo
country: Brazil
facility: Novartis Investigative Site
state: SP
city: Edmonton
country: Canada
facility: Novartis Investigative Site
state: Alberta
city: Vancouver
country: Canada
facility: Novartis Investigative Site
state: British Columbia
city: Halifax
country: Canada
facility: Novartis Investigative Site
state: Nova Scotia
city: Montreal
country: Canada
facility: Novartis Investigative Site
state: Quebec
city: Sherbrooke
country: Canada
facility: Novartis Investigative Site
state: Quebec
city: Beijing
country: China
facility: Novartis Investigative Site
state: Beijing
city: Shanghai
country: China
facility: Novartis Investigative Site
city: Bogota
country: Colombia
facility: Novartis Investigative Site
state: Cundinamarca
city: Prague 2
country: Czechia
facility: Novartis Investigative Site
state: Czech republic
city: Aalborg
country: Denmark
facility: Novartis Investigative Site
city: Copenhagen
country: Denmark
facility: Novartis Investigative Site
city: Bois Guillaume Cedex
country: France
facility: Novartis Investigative Site
city: Bron Cedex
country: France
facility: Novartis Investigative Site
city: Le Kremlin Bicetre
country: France
facility: Novartis Investigative Site
city: Marseille cedex 05
country: France
facility: Novartis Investigative Site
city: Montpellier Cedex 5
country: France
facility: Novartis Investigative Site
city: Paris
country: France
facility: Novartis Investigative Site
city: Pessac Cedex
country: France
facility: Novartis Investigative Site
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Erlangen
country: Germany
facility: Novartis Investigative Site
city: Essen
country: Germany
facility: Novartis Investigative Site
city: Muenchen
country: Germany
facility: Novartis Investigative Site
city: Athens
country: Greece
facility: Novartis Investigative Site
state: GR
city: Pireas
country: Greece
facility: Novartis Investigative Site
city: Budapest
country: Hungary
facility: Novartis Investigative Site
city: Jerusalem
country: Israel
facility: Novartis Investigative Site
city: Petach Tikva
country: Israel
facility: Novartis Investigative Site
city: Cona
country: Italy
facility: Novartis Investigative Site
state: FE
city: Genova
country: Italy
facility: Novartis Investigative Site
state: GE
city: Padova
country: Italy
facility: Novartis Investigative Site
state: PD
city: Pisa
country: Italy
facility: Novartis Investigative Site
state: PI
city: Roma
country: Italy
facility: Novartis Investigative Site
state: RM
city: Torino
country: Italy
facility: Novartis Investigative Site
state: TO
city: Napoli
country: Italy
facility: Novartis Investigative Site
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
state: Korea
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
state: Korea
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
state: Korea
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
city: Mexico
country: Mexico
facility: Novartis Investigative Site
state: Distrito Federal
city: México
country: Mexico
facility: Novartis Investigative Site
state: Distrito Federal
city: Nijmegen
country: Netherlands
facility: Novartis Investigative Site
city: Rotterdam
country: Netherlands
facility: Novartis Investigative Site
city: Bergen
country: Norway
facility: Novartis Investigative Site
city: Oslo
country: Norway
facility: Novartis Investigative Site
city: Krakow
country: Poland
facility: Novartis Investigative Site
city: Warszawa
country: Poland
facility: Novartis Investigative Site
city: Moscow
country: Russian Federation
facility: Novartis Investigative Site
city: Moscow
country: Russian Federation
facility: Novartis Investigative Site
city: Saint Petersburg
country: Russian Federation
facility: Novartis Investigative Site
city: Saint-Petersburg
country: Russian Federation
facility: Novartis Investigative Site
city: Sevilla
country: Spain
facility: Novartis Investigative Site
state: Andalucia
city: Hospitalet de Llobregat
country: Spain
facility: Novartis Investigative Site
state: Barcelona
city: Alicante
country: Spain
facility: Novartis Investigative Site
state: Comunidad Valenciana
city: Santiago de Compostela
country: Spain
facility: Novartis Investigative Site
state: Galicia
city: Linkoping
country: Sweden
facility: Novartis Investigative Site
city: Malmö
country: Sweden
facility: Novartis Investigative Site
city: Uppsala
country: Sweden
facility: Novartis Investigative Site
city: St. Gallen
country: Switzerland
facility: Novartis Investigative Site
city: Lin-Kou
country: Taiwan
facility: Novartis Investigative Site
city: Taichung
country: Taiwan
facility: Novartis Investigative Site
city: Taipei
country: Taiwan
facility: Novartis Investigative Site
city: Ankara
country: Turkey
facility: Novartis Investigative Site
city: Erzurum
country: Turkey
facility: Novartis Investigative Site
city: Leeds
country: United Kingdom
facility: Novartis Investigative Site
city: Liverpool
country: United Kingdom
facility: Novartis Investigative Site
city: London
country: United Kingdom
facility: Novartis Investigative Site
city: Southampton
country: United Kingdom
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
affiliation: Novartis
name: Novartis
role: STUDY_CHAIR
References:
citation: Bronstein MD, Fleseriu M, Neggers S, Colao A, Sheppard M, Gu F, Shen CC, Gadelha M, Farrall AJ, Hermosillo Resendiz K, Ruffin M, Chen Y, Freda P; Pasireotide C2305 Study Group. Switching patients with acromegaly from octreotide to pasireotide improves biochemical control: crossover extension to a randomized, double-blind, Phase III study. BMC Endocr Disord. 2016 Apr 2;16:16. doi: 10.1186/s12902-016-0096-8.
citation: Shanik MH, Cao PD, Ludlam WH. HISTORICAL RESPONSE RATES OF SOMATOSTATIN ANALOGUES IN THE TREATMENT OF ACROMEGALY: A SYSTEMATIC REVIEW. Endocr Pract. 2016 Mar;22(3):350-6. doi: 10.4158/EP15913.RA. Epub 2015 Oct 5.
citation: Sheppard M, Bronstein MD, Freda P, Serri O, De Marinis L, Naves L, Rozhinskaya L, Hermosillo Resendiz K, Ruffin M, Chen Y, Colao A. Pasireotide LAR maintains inhibition of GH and IGF-1 in patients with acromegaly for up to 25 months: results from the blinded extension phase of a randomized, double-blind, multicenter, Phase III study. Pituitary. 2015 Jun;18(3):385-94. doi: 10.1007/s11102-014-0585-6.