Clinical trial NCT01137682: Efficacy and Safety of Pasireotide Long Acting Release (LAR) Versus Octreotide LAR or Lanreotide Autogel (ATG) in Patients With Inadequately Controlled Acromegaly
Official title: A Phase III, Multicenter, Randomized, Parallel-group Study to Assess the Efficacy and Safety of Double-blind Pasireotide LAR 40 mg and Pasireotide LAR 60 mg Versus Open-label Octreotide LAR or Lanreotide ATG in Patients With Inadequately Controlled Acromegaly
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Acromegaly
Keywords: Acromegaly
hormone disorder
growth hormone
insulin like growth factor-1
pituitary tumor
pasireotide
SOM230
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2010-06-04
Enrollment: 198
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: This study will evaluate the efficacy and safety of pasireotide LAR 40 and 60 mg versus octreotide LAR or lanreotide ATG in patients with inadequately controlled acromegaly.


Eligibility criteria: Inclusion Criteria:

1. Patients with written informed consent prior to any study related activity
2. Patients who had inadequately controlled acromegaly as defined by a mean GH concentration of a 5-point profile over a 2-hour period \> 2.5 µg/L and sex- and age-adjusted IGF-1 \> 1.3 x upper limit of normal (ULN)
3. Patients who had been treated with maximum indicated doses of octreotide LAR or lanreotide ATG for at least 6 months prior to visit 1 (screening). The maximum indicated dose for octreotide LAR was 30mg and for lanreotide ATG iwas120 mg
4. Patients who had a diagnosis of pituitary micro- or macro adenoma. Patients could have been previously submitted to surgery
5. Patients who completed the 24-week treatment period in core according to the requirements of the core study protocol or corresponding amendments could enter extension

Exclusion Criteria:

1. Patients who had received pasireotide (SOM 230) prior to enrolment
2. Concomitant treatment with Growth Hormone Receptor (GHR)-antagonist or dopamine agonists unless concomitant treatment was discontinued 8 weeks prior to visit 1 (screening)(8 weeks wash out period). Such patients must have been treated with octreotide LAR 30 mg or lanreotide ATG 120 mg monotherapy continuously for a minimum of 6 months prior to starting combination therapy and they should have been inadequately controlled on monotherapy.
3. Patients who had compression of the optic chiasm causing acute clinically significant visual field defects
4. Patients who required a surgical intervention for relief of any sign or symptom associated with tumor compression
5. Patients who had received pituitary irradiation within 10 years prior to visit 1 (screening).
6. Patients who had undergone major surgery/surgical therapy for any cause within 4 weeks prior to visit 1 (screening).
7. Patients who were hypothyroid and not adequately treated with a stable dose of thyroid hormone replacement therapy

Primary outcomes:
measure: Percentage of Participants With a Reduction of Mean GH Levels to < 2.5 µg/L and Normalization of Sex- and Age-adjusted IGF-1.
timeFrame: At 24 weeks
Secondary outcomes:
measure: Percentage of Patients With Mean GH < 2.5 μg/L and Normalization of IGF-1, Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly (Extension Full Analysis Set)
timeFrame: Extension baseline up to approximately week 268
measure: Percentage of Participants With Normalization of Sex- and Age-adjusted IGF-1treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly (Extension Full Analysis Set).
timeFrame: Extension baseline up to approximately week 268
measure: Percentage of Patients With Mean GH < 2.5 μg/L Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly (Extension Full Analysis Set)
timeFrame: Extension baseline up to approximately week 268
measure: Percentage of Patients With Mean GH < 1.0 μg/L and Normalization of IGF-1, Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly (Extension Full Analysis Set)
timeFrame: Extension baseline up to approximately week 268
measure: Percentage of Patients With Mean GH <1.0 μg/L Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly (Extension Full Analysis Set)
timeFrame: Extension baseline up to approximately week 268
measure: Change From Baseline in Mean GH Values for Patients Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly for CORE Visits (Extension Full Analysis Set)
timeFrame: CORE baseline up to approximately 24 weeks
measure: Change From Baseline in Mean GH Values for Patients Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly for Extension Visits (Extension Full Analysis Set)
timeFrame: CORE and extension baseline up to approximately 268 weeks
measure: Change From Baseline in Standardized IGF-1 Values for Patients Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly for CORE Visits (Extension Full Analysis Set)
timeFrame: CORE baseline up to approximately 24 weeks
measure: Change From Baseline in Standardized IGF-1 Values for Patients Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly for Extension Visits (Extension Full Analysis Set)
timeFrame: CORE and extension baseline up to approximately 268 weeks
measure: Duration of the First Response for Patients Achieving a Reduction of Mean GH Level to < 2.5 μg/L and Normalization of IGF-1 and Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly (Extension Full Analysis Set)
timeFrame: CORE baseline up to approximately 268 weeks
measure: Time to First Response (Weeks) by Treatment for Patients Achieving a Reduction of Mean GH Level to < 2.5 µg/L and Normalization of IGF-1 and Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly
timeFrame: CORE baseline up to approximately 268 weeks
measure: Change From Baseline in AcroQoL Total Scores for Patients Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly for CORE Visits(Extension Full Analysis Set)
timeFrame: CORE baseline up to approximately 24 weeks
measure: Change From Baseline in AcroQoL Total Scores for Patients Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly for Extension Visits (Extension Full Analysis Set)
timeFrame: CORE Baseline and extension baseline up to approximately 268 weeks
measure: Summary of Pasireotide Trough Concentrations in Acromegaly Patients Following Monthly i.m. Injections of Pasireotide LAR by Incident Dose From Start of Extension Phase up to Week 196 of the Extension Phase (PK Set)
timeFrame: Extension baseline up to approximately 196 weeks
Other outcomes:
Locations:
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Portland
country: United States
facility: Oregon Health & Science University
state: Oregon
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center Division of Hematology/Oncolog
state: Texas
city: Seattle
country: United States
facility: Swedish Neuroscience Institute 550 17th Avenue, Suite 500
state: Washington
city: Caba
country: Argentina
facility: Novartis Investigative Site
state: Buenos Aires
city: Edegem
country: Belgium
facility: Novartis Investigative Site
state: Antwerpen
city: Brussels
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: Sao Luis
country: Brazil
facility: Novartis Investigative Site
state: MA
city: Rio de Janeiro
country: Brazil
facility: Novartis Investigative Site
state: RJ
city: Joinville
country: Brazil
facility: Novartis Investigative Site
state: SC
city: Botucatu
country: Brazil
facility: Novartis Investigative Site
state: SP
city: Campinas
country: Brazil
facility: Novartis Investigative Site
state: SP
city: Sao Paulo
country: Brazil
facility: Novartis Investigative Site
state: SP
city: São Paulo
country: Brazil
facility: Novartis Investigative Site
state: SP
city: Sherbrooke
country: Canada
facility: Novartis Investigative Site
state: Quebec
city: Bogota
country: Colombia
facility: Novartis Investigative Site
state: Cundinamarca
city: Bogotá
country: Colombia
facility: Novartis Investigative Site
city: Cali
country: Colombia
facility: Novartis Investigative Site
city: Toulouse
country: France
facility: Novartis Investigative Site
state: Cedex 9
city: Bron
country: France
facility: Novartis Investigative Site
state: Cedex
city: Dijon
country: France
facility: Novartis Investigative Site
city: Le Kremlin Bicetre
country: France
facility: Novartis Investigative Site
city: Lille
country: France
facility: Novartis Investigative Site
city: Marseille
country: France
facility: Novartis Investigative Site
city: Paris
country: France
facility: Novartis Investigative Site
city: Pessac Cedex
country: France
facility: Novartis Investigative Site
city: Rennes Cedex
country: France
facility: Novartis Investigative Site
city: Saint Herblain - Nantes
country: France
facility: Novartis Investigative Site
city: Erlangen
country: Germany
facility: Novartis Investigative Site
city: Hamburg
country: Germany
facility: Novartis Investigative Site
city: Muenchen
country: Germany
facility: Novartis Investigative Site
city: Wurzburg
country: Germany
facility: Novartis Investigative Site
city: Petach Tikva
country: Israel
facility: Novartis Investigative Site
city: Genova
country: Italy
facility: Novartis Investigative Site
state: GE
city: Messina
country: Italy
facility: Novartis Investigative Site
state: ME
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: Bergen
country: Norway
facility: Novartis Investigative Site
city: Oslo
country: Norway
facility: Novartis Investigative Site
city: Gdansk
country: Poland
facility: Novartis Investigative Site
city: Poznan
country: Poland
facility: Novartis Investigative Site
city: Wroclaw
country: Poland
facility: Novartis Investigative Site
city: Bucuresti
country: Romania
facility: Novartis Investigative Site
city: Barnaul
country: Russian Federation
facility: Novartis Investigative Site
city: Moscow
country: Russian Federation
facility: Novartis Investigative Site
city: Moscow
country: Russian Federation
facility: Novartis Investigative Site
city: Tyumen
country: Russian Federation
facility: Novartis Investigative Site
city: Jeddah
country: Saudi Arabia
facility: Novartis Investigative Site
city: Riyadh
country: Saudi Arabia
facility: Novartis Investigative Site
city: Sevilla
country: Spain
facility: Novartis Investigative Site
state: Andalucia
city: Barcelona
country: Spain
facility: Novartis Investigative Site
state: Catalunya
city: Alicante
country: Spain
facility: Novartis Investigative Site
state: Comunidad Valenciana
city: Altunizade
country: Turkey
facility: Novartis Investigative Site
city: Antalya
country: Turkey
facility: Novartis Investigative Site
city: Izmir
country: Turkey
facility: Novartis Investigative Site
city: Plymouth
country: United Kingdom
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References:
citation: Colao A, Bronstein MD, Brue T, De Marinis L, Fleseriu M, Guitelman M, Raverot G, Shimon I, Fleck J, Gupta P, Pedroncelli AM, Gadelha MR. Pasireotide for acromegaly: long-term outcomes from an extension to the Phase III PAOLA study. Eur J Endocrinol. 2020 Jun;182(6):583. doi: 10.1530/EJE-19-0762.
citation: Gadelha MR, Bronstein MD, Brue T, Coculescu M, Fleseriu M, Guitelman M, Pronin V, Raverot G, Shimon I, Lievre KK, Fleck J, Aout M, Pedroncelli AM, Colao A; Pasireotide C2402 Study Group. Pasireotide versus continued treatment with octreotide or lanreotide in patients with inadequately controlled acromegaly (PAOLA): a randomised, phase 3 trial. Lancet Diabetes Endocrinol. 2014 Nov;2(11):875-84. doi: 10.1016/S2213-8587(14)70169-X. Epub 2014 Sep 24.