This site became the new ClinicalTrials.gov on June 19th. Learn more.
Show more
ClinicalTrials.gov Menu IMPORTANT: Listing of a study on this site does not reflect endorsement by the National Institutes of Health. Talk with a trusted healthcare professional before volunteering for a study. Read more...
ClinicalTrials.gov Menu IMPORTANT: Talk with a trusted healthcare professional before volunteering for a study. Read more...
ClinicalTrials.gov Menu
Give us feedback

Efficacy and Safety of Pasireotide Long Acting Release (LAR) Versus Octreotide LAR or Lanreotide Autogel (ATG) in Patients With Inadequately Controlled Acromegaly (PAOLA)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01137682
First received: May 27, 2010
Last updated: April 28, 2017
Last verified: April 2017
  Purpose
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.

Condition Intervention Phase
Acromegaly Drug: Pasireotide (SOM230) Drug: octreotide LAR 30mg Drug: lanreotide ATG 120mg Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Participant, Care Provider, Investigator, Outcomes Assessor
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Novartis ( Novartis Pharmaceuticals ):

Primary Outcome Measures:
  • Percentage of Participants With a Reduction of Mean GH Levels to < 2.5 µg/L and Normalization of Sex- and Age-adjusted IGF-1. [ Time Frame: 24 weeks ]
    The primary objective of this study was to compare the proportion of patients achieving biochemical control (defined as mean GH levels <2.5 µg/L and normalization of sex- and age- adjusted IGF-1) at 24 weeks with pasireotide LAR 40 mg and pasireotide LAR 60 mg separately versus continued treatment with octreotide LAR 30 mg or lanreotide autogel (ATG) 120 mg. The primary efficacy variable is the proportion of patients with a reduction of mean GH levels to < 2.5 µg/L and normalization of sex- and age-adjusted IGF-1 at 24 weeks.


Secondary Outcome Measures:
  • Perecentage of Participants Achieving Normalization of Sex- and Age-adjusted IGF-1 [ Time Frame: 24 weeks ]
    The key secondary objective is to compare the effect of pasireotide LAR (40 mg and 60 mg separately) versus continuing the same treatment on the proportion of patients achieving normalization of sex- and age-adjusted IGF-1 at 24 weeks. The endpoint for the key secondary objective is the proportion of patients achieving normalization of sex- and age-adjusted IGF-1 at 24 weeks.

  • Percentage of Participants Achieving Biochemical Control Defined as Mean GH Levels < 2.5 µg/L and Normalization of Sex- and Age-adjusted IGF-1. [ Time Frame: 12 Weeks ]
  • Percentage of Participants Achieving GH Levels < 2.5 µg/L. [ Time Frame: Weeks 12 and 24 ]
  • Percentage of of Participants Achieving GH Levels < 1 µg/L and Normal, Sex- and Age-adjusted IGF-1. [ Time Frame: Weeks 12 and 24 ]
  • Percentage of Participants Achieving GH Levels < 1 µg/L. [ Time Frame: Weeks 12 and 24 ]
  • Percentage of Participants Achieving a Tumor Volume Reduction > 25% Assessed by Pituitary MRI. [ Time Frame: 24 Weeks ]
  • Percent Change in Tumor Volume Assessed by Pituitary MRI. [ Time Frame: Baseline, 24 Weeks ]
  • Change From Baseline in Clinical Signs/Symptoms of Acromegaly (Ring Size; Headache, Fatigue, Perspiration, Paresthesias and Osteoarthralgia According to a Five-point Score Scale) [ Time Frame: Baseline, 24 Weeks ]
  • Change From Baseline in Health Related QoL as Measured by the AcroQoL (Acromegaly Health Related QoL) [ Time Frame: Baseline, 24 Weeks ]
  • PK Levels of Pasireotide LAR 40 mg and Pasireotide LAR 60 mg [ Time Frame: 24 Weeks ]

Enrollment: 198
Actual Study Start Date: July 19, 2010
Study Completion Date: February 27, 2017
Primary Completion Date: January 22, 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Pasireotide LAR 40 mg
Supplied in blinded fashion as 20 and 40 mg powder in vials and 2 mL vehicle in ampoule (for reconstitution)
Drug: Pasireotide (SOM230)
  • Double-blind pasireotide LAR 40 mg i.m. injection once every 28 ± 2 days for 24 weeks or
  • Double-blind pasireotide LAR 60 mg i.m. injection once every 28 ± 2 days for 24 weeks
Experimental: Pasireotide LAR 60 mg
Supplied in blinded fashion as 20 and 40 mg powder in vials and 2 mL vehicle in ampoule (for reconstitution)
Drug: Pasireotide (SOM230)
  • Double-blind pasireotide LAR 40 mg i.m. injection once every 28 ± 2 days for 24 weeks or
  • Double-blind pasireotide LAR 60 mg i.m. injection once every 28 ± 2 days for 24 weeks
Active Comparator: Control arm (octreotide or lanreotide)

If a patient is randomized to the open label arm the investigator will either:

  • be instructed to contact a Novartis delegate to initiate shipment of either octreotide LAR 30 mg or lanreotide ATG 120 mg from a Novartis or designee depot to the site, or
  • continue to dispense either octreotide LAR 30 mg or lanreotide ATG 120 mg available at the institution to the patient if permitted by local regulations.
Drug: octreotide LAR 30mg
In an open-label, active control arm, continue on the same treatment with octreotide LAR 30 mg every 28 ± 2 days as received for at least 6 months prior to randomization
Drug: lanreotide ATG 120mg
In an open-label, active control arm, continue on the same treatment with lanreotide ATG 120 mg every 28 ± 2 days as received for at least 6 months prior to randomization

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Patients with written informed consent prior to any study related activity
  2. Patients with 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 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 is 30mg and for lanreotide ATG is 120 mg
  4. Patients with diagnosis of pituitary micro- or macro adenoma. Patients can have been previously submitted to surgery

Exclusion Criteria:

  1. Patients who have 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 with compression of the optic chiasm causing acute clinically significant visual field defects
  4. Patients who require a surgical intervention for relief of any sign or symptom associated with tumor compression
  5. Patients who have received pituitary irradiation within 10 years prior to visit 1 (screening).
  6. Patients who have undergone major surgery/surgical therapy for any cause within 4 weeks prior to visit 1 (screening).
  7. Patients who are hypothyroid and not adequately treated with a stable dose of thyroid hormone replacement therapy

Other protocol-defined inclusion/exclusion criteria may apply

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01137682

  Hide Study Locations
Locations
United States, Michigan
University of Michigan
Ann Arbor, Michigan, United States, 48109
United States, Oregon
Oregon Health & Science University
Portland, Oregon, United States, 97239
United States, Texas
University of Texas Southwestern Medical Center Division of Hematology/Oncolog
Dallas, Texas, United States, 75235
United States, Washington
Swedish Neuroscience Institute 550 17th Avenue, Suite 500
Seattle, Washington, United States, 98122
Argentina
Novartis Investigative Site
Caba, Buenos Aires, Argentina, C1405BCH
Belgium
Novartis Investigative Site
Brussels, Belgium, BE-B-1200
Novartis Investigative Site
Edegem, Belgium, 2650
Novartis Investigative Site
Gent, Belgium, 9000
Novartis Investigative Site
Leuven, Belgium, 3000
Brazil
Novartis Investigative Site
Fortaleza, CE, Brazil, 60430 370
Novartis Investigative Site
Sao Luis, MA, Brazil, 65020-070
Novartis Investigative Site
Rio de Janeiro, RJ, Brazil, 21941-913
Novartis Investigative Site
Joinville, SC, Brazil, 89201260
Novartis Investigative Site
Botucatu, SP, Brazil, 18618-970
Novartis Investigative Site
Campinas, SP, Brazil, 13083-970
Novartis Investigative Site
Sao Paulo, SP, Brazil, 05403-000
Novartis Investigative Site
São Paulo, SP, Brazil, 04038-002
Canada, Quebec
Novartis Investigative Site
Sherbrooke, Quebec, Canada, J1H 5N4
Colombia
Novartis Investigative Site
Bogota, Cundinamarca, Colombia, 111411
Novartis Investigative Site
Bogotá, Colombia, 00000
Novartis Investigative Site
Cali, Colombia
France
Novartis Investigative Site
Bron, France, 69677
Novartis Investigative Site
Dijon, France, 21034
Novartis Investigative Site
Le Kremlin Bicetre, France, 94275
Novartis Investigative Site
Lille, France, 59037
Novartis Investigative Site
Marseille, France, 13005
Novartis Investigative Site
Pessac Cedex, France, 33604
Novartis Investigative Site
Rennes Cedex, France, 35022
Novartis Investigative Site
St Herblain - Nantes, France, 44093
Novartis Investigative Site
Toulouse Cedex 9, France, 31000
Germany
Novartis Investigative Site
Erlangen, Germany, 91054
Novartis Investigative Site
Hamburg, Germany, 22587
Novartis Investigative Site
Muenchen, Germany, 80336
Novartis Investigative Site
Würzburg, Germany, 97080
Israel
Novartis Investigative Site
Petach Tikva, Israel, 49100
Italy
Novartis Investigative Site
Genova, GE, Italy, 16132
Novartis Investigative Site
Messina, ME, Italy, 98125
Novartis Investigative Site
Roma, RM, Italy, 00168
Novartis Investigative Site
Torino, TO, Italy, 10126
Novartis Investigative Site
Napoli, Italy, 80131
Norway
Novartis Investigative Site
Bergen, Norway, NO-5021
Novartis Investigative Site
Oslo, Norway, NO-0379
Poland
Novartis Investigative Site
Gdansk, Poland, 80-952
Novartis Investigative Site
Poznan, Poland, 60-355
Novartis Investigative Site
Wroclaw, Poland, 50-367
Romania
Novartis Investigative Site
Bucuresti, Romania, 011863
Russian Federation
Novartis Investigative Site
Barnaul, Russian Federation, 656024
Novartis Investigative Site
Moscow, Russian Federation, 117036
Novartis Investigative Site
Moscow, Russian Federation, 119992
Novartis Investigative Site
Tyumen, Russian Federation, 625023
Saudi Arabia
Novartis Investigative Site
Jeddah, Saudi Arabia, 21423
Novartis Investigative Site
Riyadh, Saudi Arabia, 11211
Spain
Novartis Investigative Site
Sevilla, Andalucia, Spain, 41013
Novartis Investigative Site
Barcelona, Catalunya, Spain, 08035
Novartis Investigative Site
Alicante, Comunidad Valenciana, Spain, 03010
Turkey
Novartis Investigative Site
Altunizade, Turkey, 34662
Novartis Investigative Site
Antalya, Turkey, 07070
Novartis Investigative Site
Balcova / Izmir, Turkey, 35340
United Kingdom
Novartis Investigative Site
Plymouth, United Kingdom, PL6 8DH
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT01137682     History of Changes
Other Study ID Numbers: CSOM230C2402
EUDRACT 2009-016722-13 ( Registry Identifier: EUDRACT )
Study First Received: May 27, 2010
Results First Received: January 13, 2015
Last Updated: April 28, 2017
Individual Participant Data  
Plan to Share IPD: Undecided

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Novartis ( Novartis Pharmaceuticals ):
Acromegaly
hormone disorder
growth hormone
insulin like growth factor-1
pituitary tumor

Additional relevant MeSH terms:
Acromegaly
Bone Diseases, Endocrine
Bone Diseases
Musculoskeletal Diseases
Hyperpituitarism
Pituitary Diseases
Hypothalamic Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Endocrine System Diseases
Octreotide
Lanreotide
Angiopeptin
Somatostatin
Gastrointestinal Agents
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on June 26, 2017