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

NCT ID: NCT01137682

Last Updated: 2018-04-05

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

198 participants

Study Classification

INTERVENTIONAL

Study Start Date

2010-07-19

Study Completion Date

2017-02-28

Brief Summary

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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.

Detailed Description

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Conditions

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Acromegaly

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Pasireotide LAR 40 mg

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

Group Type EXPERIMENTAL

Pasireotide

Intervention Type 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

Pasireotide LAR 60 mg

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

Group Type EXPERIMENTAL

Pasireotide

Intervention Type 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

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.

Group Type ACTIVE_COMPARATOR

octreotide LAR 30mg

Intervention Type 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

lanreotide ATG 120mg

Intervention Type 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

Interventions

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Pasireotide

* 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

Intervention Type 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

Intervention Type 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

Intervention Type DRUG

Other Intervention Names

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SOM230

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Novartis Pharmaceuticals

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Novartis Pharmaceuticals

Role: STUDY_DIRECTOR

Novartis Pharmaceuticals

Locations

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University of Michigan

Ann Arbor, Michigan, United States

Site Status

Oregon Health & Science University

Portland, Oregon, United States

Site Status

University of Texas Southwestern Medical Center Division of Hematology/Oncolog

Dallas, Texas, United States

Site Status

Swedish Neuroscience Institute 550 17th Avenue, Suite 500

Seattle, Washington, United States

Site Status

Novartis Investigative Site

CABA, Buenos Aires, Argentina

Site Status

Novartis Investigative Site

Edegem, Antwerpen, Belgium

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Novartis Investigative Site

Brussels, , Belgium

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Novartis Investigative Site

Ghent, , Belgium

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Novartis Investigative Site

Leuven, , Belgium

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Novartis Investigative Site

Fortaleza, Ceará, Brazil

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Novartis Investigative Site

São Luís, Maranhão, Brazil

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Novartis Investigative Site

Rio de Janeiro, Rio de Janeiro, Brazil

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Novartis Investigative Site

Joinville, Santa Catarina, Brazil

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Novartis Investigative Site

Botucatu, São Paulo, Brazil

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Novartis Investigative Site

Campinas, São Paulo, Brazil

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São Paulo, São Paulo, Brazil

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São Paulo, São Paulo, Brazil

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Novartis Investigative Site

Sherbrooke, Quebec, Canada

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Novartis Investigative Site

Bogota, Cundinamarca, Colombia

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Novartis Investigative Site

Bogotá, , Colombia

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Novartis Investigative Site

Cali, , Colombia

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Novartis Investigative Site

Toulouse, Cedex 9, France

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Novartis Investigative Site

Bron, Cedex, France

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Novartis Investigative Site

Dijon, , France

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Novartis Investigative Site

Le Kremlin-Bicêtre, , France

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Lille, , France

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Marseille, , France

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Paris, , France

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Pessac, , France

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Rennes, , France

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Novartis Investigative Site

Saint Herblain - Nantes, , France

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Novartis Investigative Site

Erlangen, , Germany

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Novartis Investigative Site

Hamburg, , Germany

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Novartis Investigative Site

München, , Germany

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Novartis Investigative Site

Würzburg, , Germany

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Novartis Investigative Site

Petah Tikva, , Israel

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Novartis Investigative Site

Genova, GE, Italy

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Messina, ME, Italy

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Roma, RM, Italy

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Torino, TO, Italy

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Napoli, , Italy

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Bergen, , Norway

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Oslo, , Norway

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Gdansk, , Poland

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Poznan, , Poland

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Wroclaw, , Poland

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Bucharest, , Romania

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Barnaul, , Russia

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Moscow, , Russia

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Moscow, , Russia

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Tyumen, , Russia

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Novartis Investigative Site

Jeddah, , Saudi Arabia

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Novartis Investigative Site

Riyadh, , Saudi Arabia

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Novartis Investigative Site

Seville, Andalusia, Spain

Site Status

Novartis Investigative Site

Barcelona, Catalonia, Spain

Site Status

Novartis Investigative Site

Alicante, Valencia, Spain

Site Status

Novartis Investigative Site

Altunizade, , Turkey (Türkiye)

Site Status

Novartis Investigative Site

Antalya, , Turkey (Türkiye)

Site Status

Novartis Investigative Site

Izmir, , Turkey (Türkiye)

Site Status

Novartis Investigative Site

Plymouth, , United Kingdom

Site Status

Countries

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United States Argentina Belgium Brazil Canada Colombia France Germany Israel Italy Norway Poland Romania Russia Saudi Arabia Spain Turkey (Türkiye) United Kingdom

References

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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.

Reference Type DERIVED
PMID: 32217809 (View on PubMed)

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.

Reference Type DERIVED
PMID: 25260838 (View on PubMed)

Other Identifiers

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EUDRACT 2009-016722-13

Identifier Type: REGISTRY

Identifier Source: secondary_id

CSOM230C2402

Identifier Type: -

Identifier Source: org_study_id

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