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

NCT01137682 | Completed Phase 3 Results FDA Drug

• 2 other identifiers: CSOM230C2402EUDRACT 2009-016722-13
• Study Type: interventional
• Target: 198
• Locations: 18 countries
• Sites: 60

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.

Conditions

Acromegaly

Keywords

Acromegaly; hormone disorder; growth hormone; insulin like growth factor-1; pituitary tumor; pasireotide; SOM230

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With a Reduction of Mean GH Levels to < 2.5 µg/L and Normalization of Sex- and Age-adjusted IGF-1.

  The primary objective of this study was to compare the percentage 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.

  At 24 weeks

Secondary Outcomes (14)

• 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)

  Extension baseline up to approximately week 268

• 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).

  Extension baseline up to approximately week 268

• 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)

  Extension baseline up to approximately week 268

• 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)

  Extension baseline up to approximately week 268

• 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)

  Extension baseline up to approximately week 268

Study Arms (3)

Pasireotide LAR 40 mg

EXPERIMENTAL

Supplied in blinded fashion as 20 and 40 mg powder in vials and 2 mL vehicle in ampoule (for reconstitution)

Drug: Pasireotide

Pasireotide LAR 60 mg

EXPERIMENTAL

Supplied in blinded fashion as 20 and 40 mg powder in vials and 2 mL vehicle in ampoule (for reconstitution)

Drug: Pasireotide

Control arm (octreotide or lanreotide)

ACTIVE COMPARATOR

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; Drug: lanreotide ATG 120mg

Interventions

Pasireotide DRUG

* 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

Also known as: SOM230

Pasireotide LAR 40 mg; Pasireotide LAR 60 mg

octreotide LAR 30mg DRUG

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

Control arm (octreotide or lanreotide)

lanreotide ATG 120mg DRUG

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

Control arm (octreotide or lanreotide)

Eligibility Criteria

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

You may qualify if:

• Patients with written informed consent prior to any study related activity
• 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)
• 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
• Patients who had a diagnosis of pituitary micro- or macro adenoma. Patients could have been previously submitted to surgery
• 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

You may not qualify if:

• Patients who had received pasireotide (SOM 230) prior to enrolment
• 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.
• Patients who had compression of the optic chiasm causing acute clinically significant visual field defects
• Patients who required a surgical intervention for relief of any sign or symptom associated with tumor compression
• Patients who had received pituitary irradiation within 10 years prior to visit 1 (screening).
• Patients who had undergone major surgery/surgical therapy for any cause within 4 weeks prior to visit 1 (screening).
• Patients who were hypothyroid and not adequately treated with a stable dose of thyroid hormone replacement therapy

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (60)

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

Oregon Health & Science University

Portland, Oregon, 97239, United States

Location

University of Texas Southwestern Medical Center Division of Hematology/Oncolog

Dallas, Texas, 75235, United States

Location

Swedish Neuroscience Institute 550 17th Avenue, Suite 500

Seattle, Washington, 98122, United States

Location

Novartis Investigative Site

CABA, Buenos Aires, C1405BCH, Argentina

Location

Novartis Investigative Site

Edegem, Antwerpen, 2650, Belgium

Location

Novartis Investigative Site

Brussels, BE-B-1200, 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

São Luís, Maranhão, 65020-070, Brazil

Location

Novartis Investigative Site

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

Location

Novartis Investigative Site

Joinville, Santa Catarina, 89201260, Brazil

Location

Novartis Investigative Site

Botucatu, São Paulo, 18618-970, Brazil

Location

Novartis Investigative Site

Campinas, São Paulo, 13083-970, Brazil

Location

Novartis Investigative Site

São Paulo, São Paulo, 04038-002, Brazil

Location

Novartis Investigative Site

São Paulo, São Paulo, 05403 000, Brazil

Location

Novartis Investigative Site

Sherbrooke, Quebec, J1H 5N4, Canada

Location

Novartis Investigative Site

Bogota, Cundinamarca, 111411, Colombia

Location

Novartis Investigative Site

Bogotá, 00000, Colombia

Location

Novartis Investigative Site

Cali, Colombia

Location

Novartis Investigative Site

Toulouse, Cedex 9, 31000, France

Location

Novartis Investigative Site

Bron, Cedex, 69677, France

Location

Novartis Investigative Site

Dijon, 21034, France

Location

Novartis Investigative Site

Le Kremlin-Bicêtre, 94275, France

Location

Novartis Investigative Site

Lille, 59037, France

Location

Novartis Investigative Site

Marseille, 13005, France

Location

Novartis Investigative Site

Paris, 75571, France

Location

Novartis Investigative Site

Pessac, 33604, France

Location

Novartis Investigative Site

Rennes, 35022, France

Location

Novartis Investigative Site

Saint Herblain - Nantes, 44093, France

Location

Novartis Investigative Site

Erlangen, 91054, Germany

Location

Novartis Investigative Site

Hamburg, 22587, Germany

Location

Novartis Investigative Site

München, 80336, Germany

Location

Novartis Investigative Site

Würzburg, 97080, Germany

Location

Novartis Investigative Site

Petah Tikva, 49100, Israel

Location

Novartis Investigative Site

Genova, GE, 16132, Italy

Location

Novartis Investigative Site

Messina, ME, 98125, 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

Bergen, NO-5021, Norway

Location

Novartis Investigative Site

Oslo, NO-0379, Norway

Location

Novartis Investigative Site

Gdansk, 80-952, Poland

Location

Novartis Investigative Site

Poznan, 60-355, Poland

Location

Novartis Investigative Site

Wroclaw, 50 367, Poland

Location

Novartis Investigative Site

Bucharest, 011863, Romania

Location

Novartis Investigative Site

Barnaul, 656024, Russia

Location

Novartis Investigative Site

Moscow, 101990, Russia

Location

Novartis Investigative Site

Moscow, 117036, Russia

Location

Novartis Investigative Site

Tyumen, 625023, Russia

Location

Novartis Investigative Site

Jeddah, 21423, Saudi Arabia

Location

Novartis Investigative Site

Riyadh, 11211, Saudi Arabia

Location

Novartis Investigative Site

Seville, Andalusia, 41013, Spain

Location

Novartis Investigative Site

Barcelona, Catalonia, 08035, Spain

Location

Novartis Investigative Site

Alicante, Valencia, 03010, Spain

Location

Novartis Investigative Site

Altunizade, 34662, Turkey (Türkiye)

Location

Novartis Investigative Site

Antalya, 07070, Turkey (Türkiye)

Location

Novartis Investigative Site

Izmir, 35340, Turkey (Türkiye)

Location

Novartis Investigative Site

Plymouth, PL6 8DH, United Kingdom

Location

Related Publications (2)

• 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.

  PMID: 32217809 DERIVED

• 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.

  PMID: 25260838 DERIVED

MeSH Terms

Conditions

Acromegaly; Pituitary Neoplasms

Interventions

pasireotide

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; Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Hypothalamic Neoplasms; Supratentorial Neoplasms; Brain Neoplasms; Central Nervous System Neoplasms; Nervous System Neoplasms

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

Novartis.email@novartis.com

862-778-8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

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

Study Design

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

Study Record Dates

• First Submitted: May 27, 2010
• First Posted: June 4, 2010
• Study Start: July 19, 2010
• Primary Completion: January 22, 2013
• Study Completion: February 28, 2017
• Last Updated: April 5, 2018
• Results First Posted: January 21, 2015

Record last verified: 2018-04

Locations

CA (1); IT (5); SA (2); ES (3); RO (1); TU (3); PL (3); DE (4); FR (10); AR (1); RU (4); IL (1); CO (3); US (4); BR (8); GB (1); BE (4); NO (2)