Safety and Efficacy of Pasireotide Long Acting Release (LAR) vs. Octreotide LAR in Patients With Active Acromegaly

NCT00600886 | Completed Phase 3 Results DMC

• 2 other identifiers: CSOM230C23052007-001972-36
• Study Type: interventional
• Target: 358
• Locations: 27 countries
• Sites: 95

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.

Conditions

Acromegaly

Keywords

Acromegaly,; adult,; growth hormone,; insulin-like growth factor I,; somatostatin analogue

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With a Reduction of Mean GH Level to <2.5 μg/L and the Normalization of IGF-1

  Percentage of participants with a reduction of mean GH levels to \<2.5μg/L (based on a 5-point 2-hour profile) and normalization of sex- and age-adjusted IGF-1. Post surgery = patients with prior surgery but no previous medical treatment for acromegaly De novo = patients with de novo disease who refused pituitary surgery or for whom pituitary surgery was contraindicated.

  12 months

Secondary Outcomes (25)

• Percentage of Participants With a Reduction of Mean GH Level to < 2.5μg/L

  12 Months

• Change From Baseline in Tumor Volume at 12 Months

  Baseline, 12 Months

• Percentage of Participants With Normalization of IGF-1

  12 Months

• Percentage of Participants With a Reduction of Mean GH Level to < 2.5μg/L and Normalization of IGF-1

  Months 3, 6, 9, 12, 16, 19, 22, 25

• Summary of Mean GH Values

  Baseline, Months 3, 6, 9, 12, 16, 19, 22, 25

Study Arms (2)

Pasireotide LAR

EXPERIMENTAL

Patients in this arm received Pasireotide LAR 40 mg im depot injection, blinded, once every 28 days (± 2 days) for 12 months. Dose could be down- or up-titrated to 20 or 60 mg, respectively. Patients who responded to Pasireotide LAR (i.e. the randomized treatment) at the end of the core (Month 12), continued Pasireotide LAR treatment in the extension. Patients who did not respond to Pasireotide LAR at the end of the core (Month 12) were allowed to switch to receive Octreotide LAR in the extension.

Drug: Pasireotide

Octreotide LAR

ACTIVE COMPARATOR

Patients in this arm received Octreotide LAR 20 mg im depot injection, blinded, once every 28 days (± 2 days) for 12 months. Dose could be down- or up-titrated to 10 or 30 mg, respectively. Patients who responded to Octreotide LAR (i.e. the randomized treatment) at the end of the core (Month 12) continued Octreotide LAR treatment in the extension (up to 2 years of treatment). Patients who did not respond to Octreotide LAR at the end of the core (Month 12) were allowed to switch to receive Pasireotide LAR in the extension.

Drug: Octreotide

Interventions

Pasireotide DRUG

Pasireotide LAR - intramuscular (i.m.) depot injection given once every 28 days.

Also known as: SOM230

Pasireotide LAR

Octreotide DRUG

Octreotide LAR - i.m. depot injection given once every 28 days.

Octreotide LAR

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (95)

Cedars Sinai Medical Center The Pituitary Center

Los Angeles, California, 90048, United States

Location

University of California at Los Angeles Division of Endocrinology

Los Angeles, California, 90095, United States

Location

Stanford University Medical Center Stanford Cancer Center (3)

Stanford, California, 94304, United States

Location

University of Florida SC

Gainesville, Florida, 32610, United States

Location

Johns Hopkins University School of Medicine Dept.ofJohnsHopkinsUniv.

Baltimore, Maryland, 21205, United States

Location

University of Michigan Comprehensive Cancer Center Deptof Endocrinology&Diabetes

Ann Arbor, Michigan, 48109-0944, United States

Location

Columbia University Medical Center- New York Presbyterian Dept. of CU Collegeof Phys&Sur

New York, New York, 10032, United States

Location

Northport VA Medical Center CSOM230C2305

Northport, New York, 11768, United States

Location

Oregon Health & Sciences University DeptofOregonHealth&Sciences(3)

Portland, Oregon, 97201, United States

Location

Allegheny Endocrinology Associates

Pittsburgh, Pennsylvania, 15212, United States

Location

University of Texas Southwestern Medical Center Danziger Research Bldg.

Dallas, Texas, 75390, United States

Location

University of Texas/MD Anderson Cancer Center Regulatory -12

Houston, Texas, 77030-4009, United States

Location

Baylor College of Medicine

Houston, Texas, 77030, United States

Location

Swedish Medical Center Dept.ofSeattle Neuroscience(2)

Seattle, Washington, United States

Location

Novartis Investigative Site

CABA, Buenos Aires, C1405BCH, Argentina

Location

Novartis Investigative Site

Capital Federal, Buenos Aires, 1425EKP, Argentina

Location

Novartis Investigative Site

Buenos Aires, C1232AAC, Argentina

Location

Novartis Investigative Site

Brussels, 1070, Belgium

Location

Novartis Investigative Site

Brussels, 1090, Belgium

Location

Novartis Investigative Site

Ghent, 9000, Belgium

Location

Novartis Investigative Site

Leuven, 3000, Belgium

Location

Novartis Investigative Site

Fortaleza, Ceará, 60430 370, Brazil

Location

Novartis Investigative Site

Brasília, Federal District, 70840-901, Brazil

Location

Novartis Investigative Site

São Luís, Maranhão, 65020-070, Brazil

Location

Novartis Investigative Site

Curitiba, Paraná, 80060-900, Brazil

Location

Novartis Investigative Site

Rio de Janeiro, Rio de Janeiro, 21941-913, Brazil

Location

Novartis Investigative Site

São Paulo, São Paulo, 05403-000, Brazil

Location

Novartis Investigative Site

Edmonton, Alberta, T6G 2B7, Canada

Location

Novartis Investigative Site

Vancouver, British Columbia, V5Z 1M9, Canada

Location

Novartis Investigative Site

Halifax, Nova Scotia, B3H 2Y9, Canada

Location

Novartis Investigative Site

Montreal, Quebec, H2L 2W5, Canada

Location

Novartis Investigative Site

Sherbrooke, Quebec, J1H 5N4, Canada

Location

Novartis Investigative Site

Beijing, Beijing Municipality, 100730, China

Location

Novartis Investigative Site

Shanghai, 200025, China

Location

Novartis Investigative Site

Bogota, Cundinamarca, 111411, Colombia

Location

Novartis Investigative Site

Prague, Czech Republic, 128 02, Czechia

Location

Novartis Investigative Site

Aalborg, DK-9100, Denmark

Location

Novartis Investigative Site

Copenhagen, DK-2100, Denmark

Location

Novartis Investigative Site

Bois-Guillaume, 76233, France

Location

Novartis Investigative Site

Bron, 69677, France

Location

Novartis Investigative Site

Le Kremlin-Bicêtre, 94275, France

Location

Novartis Investigative Site

Marseille, 13385, France

Location

Novartis Investigative Site

Montpellier, 34295, France

Location

Novartis Investigative Site

Paris, 75014, France

Location

Novartis Investigative Site

Pessac, 33604, France

Location

Novartis Investigative Site

Berlin, 10098, Germany

Location

Novartis Investigative Site

Berlin, 12203, Germany

Location

Novartis Investigative Site

Erlangen, 91054, Germany

Location

Novartis Investigative Site

Essen, 45122, Germany

Location

Novartis Investigative Site

München, 80336, Germany

Location

Novartis Investigative Site

Athens, GR, 115 27, Greece

Location

Novartis Investigative Site

Piraeus, 18537, Greece

Location

Novartis Investigative Site

Budapest, 1085, Hungary

Location

Novartis Investigative Site

Jerusalem, 91120, Israel

Location

Novartis Investigative Site

Petah Tikva, 49100, Israel

Location

Novartis Investigative Site

Cona, FE, 44100, Italy

Location

Novartis Investigative Site

Genova, GE, 16132, Italy

Location

Novartis Investigative Site

Padua, PD, 35128, Italy

Location

Novartis Investigative Site

Pisa, PI, 56124, Italy

Location

Novartis Investigative Site

Roma, RM, 00168, Italy

Location

Novartis Investigative Site

Torino, TO, 10126, Italy

Location

Novartis Investigative Site

Napoli, 80131, Italy

Location

Novartis Investigative Site

Mexico City, Mexico City, 06720, Mexico

Location

Novartis Investigative Site

Mexico City, Mexico City, 06726, Mexico

Location

Novartis Investigative Site

Nijmegen, 6525 GA, Netherlands

Location

Novartis Investigative Site

Rotterdam, 3015 CE, Netherlands

Location

Novartis Investigative Site

Bergen, NO-5021, Norway

Location

Novartis Investigative Site

Oslo, NO-0379, Norway

Location

Novartis Investigative Site

Krakow, 31-531, Poland

Location

Novartis Investigative Site

Warsaw, 01 809, Poland

Location

Novartis Investigative Site

Moscow, 117036, Russia

Location

Novartis Investigative Site

Moscow, 119992, Russia

Location

Novartis Investigative Site

Saint Petersburg, 194044, Russia

Location

Novartis Investigative Site

Saint Petersburg, 197341, Russia

Location

Novartis Investigative Site

Seoul, Korea, 03722, South Korea

Location

Novartis Investigative Site

Seoul, Korea, 05505, South Korea

Location

Novartis Investigative Site

Seoul, Korea, 06351, South Korea

Location

Novartis Investigative Site

Seoul, 130-872, South Korea

Location

Novartis Investigative Site

Seville, Andalusia, 41013, Spain

Location

Novartis Investigative Site

L'Hospitalet de Llobregat, Barcelona, 08907, Spain

Location

Novartis Investigative Site

Santiago de Compostela, Galicia, 15706, Spain

Location

Novartis Investigative Site

Alicante, Valencia, 03010, Spain

Location

Novartis Investigative Site

Linköping, SE-581 85, Sweden

Location

Novartis Investigative Site

Malmo, SE-205 02, Sweden

Location

Novartis Investigative Site

Uppsala, SE-751 85, Sweden

Location

Novartis Investigative Site

Sankt Gallen, 9007, Switzerland

Location

Novartis Investigative Site

Linkou District, 33305, Taiwan

Location

Novartis Investigative Site

Taichung, 40705, Taiwan

Location

Novartis Investigative Site

Taipei, 10002, Taiwan

Location

Novartis Investigative Site

Ankara, 06100, Turkey (Türkiye)

Location

Novartis Investigative Site

Erzurum, 25240, Turkey (Türkiye)

Location

Novartis Investigative Site

Leeds, LS1 3EX, United Kingdom

Location

Novartis Investigative Site

Liverpool, L7 8XP, United Kingdom

Location

Novartis Investigative Site

London, EC1A 7BE, United Kingdom

Location

Novartis Investigative Site

Southampton, SO16 6YD, United Kingdom

Location

Related Publications (3)

• 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.

  PMID: 27039081 DERIVED

• 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.

  PMID: 26437217 DERIVED

• 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.

  PMID: 25103549 DERIVED

Related Links

• Visit NovartisClinicalTrials.com: Pre-qualify for a trial, and view a list of trials and participating study centers.

MeSH Terms

Conditions

Acromegaly

Interventions

pasireotide; Octreotide

Condition Hierarchy (Ancestors)

Bone Diseases, Endocrine; Bone Diseases; Musculoskeletal Diseases; Hyperpituitarism; Pituitary Diseases; Hypothalamic Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Peptides; Amino Acids, Peptides, and Proteins

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

862-778-8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

• Novartis

  Novartis

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 14, 2008
• First Posted: January 25, 2008
• Study Start: February 11, 2008
• Primary Completion: March 11, 2016
• Study Completion: March 11, 2016
• Last Updated: July 2, 2017
• Results First Posted: January 30, 2015

Record last verified: 2017-06

Locations

HU (1); NL (2); DE (5); RU (4); KR (4); FR (7); CA (5); DK (2); US (14); AR (3); NO (2); ES (4); TW (3); CZ (1); IL (2); CH (1); TU (2); BE (4); GR (2); CO (1); ME (2); BR (6); CN (2); SE (3); GB (4); PL (2); IT (7)