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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT01137682
Other study ID # CSOM230C2402
Secondary ID EUDRACT 2009-016
Status Completed
Phase Phase 3
First received May 27, 2010
Last updated April 2, 2018
Start date July 19, 2010
Est. completion date February 28, 2017

Study information

Verified date April 2018
Source Novartis
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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.


Recruitment information / eligibility

Status Completed
Enrollment 198
Est. completion date February 28, 2017
Est. primary completion date January 22, 2013
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility 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

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
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
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
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

Locations

Country Name City State
Argentina Novartis Investigative Site Caba Buenos Aires
Belgium Novartis Investigative Site Brussels
Belgium Novartis Investigative Site Edegem Antwerpen
Belgium Novartis Investigative Site Gent
Belgium Novartis Investigative Site Leuven
Brazil Novartis Investigative Site Botucatu SP
Brazil Novartis Investigative Site Campinas SP
Brazil Novartis Investigative Site Fortaleza CE
Brazil Novartis Investigative Site Joinville SC
Brazil Novartis Investigative Site Rio de Janeiro RJ
Brazil Novartis Investigative Site Sao Luis MA
Brazil Novartis Investigative Site Sao Paulo SP
Brazil Novartis Investigative Site São Paulo SP
Canada Novartis Investigative Site Sherbrooke Quebec
Colombia Novartis Investigative Site Bogota Cundinamarca
Colombia Novartis Investigative Site Bogotá
Colombia Novartis Investigative Site Cali
France Novartis Investigative Site Bron Cedex
France Novartis Investigative Site Dijon
France Novartis Investigative Site Le Kremlin Bicetre
France Novartis Investigative Site Lille
France Novartis Investigative Site Marseille
France Novartis Investigative Site Paris
France Novartis Investigative Site Pessac Cedex
France Novartis Investigative Site Rennes Cedex
France Novartis Investigative Site Saint Herblain - Nantes
France Novartis Investigative Site Toulouse Cedex 9
Germany Novartis Investigative Site Erlangen
Germany Novartis Investigative Site Hamburg
Germany Novartis Investigative Site Muenchen
Germany Novartis Investigative Site Wurzburg
Israel Novartis Investigative Site Petach Tikva
Italy Novartis Investigative Site Genova GE
Italy Novartis Investigative Site Messina ME
Italy Novartis Investigative Site Napoli
Italy Novartis Investigative Site Roma RM
Italy Novartis Investigative Site Torino TO
Norway Novartis Investigative Site Bergen
Norway Novartis Investigative Site Oslo
Poland Novartis Investigative Site Gdansk
Poland Novartis Investigative Site Poznan
Poland Novartis Investigative Site Wroclaw
Romania Novartis Investigative Site Bucuresti
Russian Federation Novartis Investigative Site Barnaul
Russian Federation Novartis Investigative Site Moscow
Russian Federation Novartis Investigative Site Moscow
Russian Federation Novartis Investigative Site Tyumen
Saudi Arabia Novartis Investigative Site Jeddah
Saudi Arabia Novartis Investigative Site Riyadh
Spain Novartis Investigative Site Alicante Comunidad Valenciana
Spain Novartis Investigative Site Barcelona Catalunya
Spain Novartis Investigative Site Sevilla Andalucia
Turkey Novartis Investigative Site Altunizade
Turkey Novartis Investigative Site Antalya
Turkey Novartis Investigative Site Izmir
United Kingdom Novartis Investigative Site Plymouth
United States University of Michigan Ann Arbor Michigan
United States University of Texas Southwestern Medical Center Division of Hematology/Oncolog Dallas Texas
United States Oregon Health & Science University Portland Oregon
United States Swedish Neuroscience Institute 550 17th Avenue, Suite 500 Seattle Washington

Sponsors (1)

Lead Sponsor Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Argentina,  Belgium,  Brazil,  Canada,  Colombia,  France,  Germany,  Israel,  Italy,  Norway,  Poland,  Romania,  Russian Federation,  Saudi Arabia,  Spain,  Turkey,  United Kingdom, 

Outcome

Type Measure Description Time frame Safety issue
Primary 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 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) The percentage of patients achieving mean growth hormone (GH) levels < 2.5 µg/L and normalization of sex and age-adjusted IGF-1 was calculated with two sided 95% confidence interval. All GH assessments were based on a 5-point mean growth hormone (GH) assessed from a 2-hour profile. Scheduled time points for blood sampling were pre-dose at 0, 30, 60, 90 and 120 minutes. Total insulin-like growth factor (IGF-1) levels were assessed with one pre-dose sample at the same visits as GH. Concomitant medication known to affect GH or IGF-1 levels were allowed in patients who were not biochemically controlled after at least one year treatment with pasireotide LAR monotherapy: dopamine agonists and growth hormone receptor antagonists (extension full analysis set) Extension baseline up to approximately week 268
Secondary 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). The percentage of patients achieving normalization of sex and age-adjusted IGF-1 was calculated with two sided 95% confidence interval. Total insulin-like growth factor (IGF-1) levels were assessed with one pre-dose sample at the same visits as GH. Concomitant medication known to affect IGF-1 levels were allowed in patients who were not biochemically controlled after at least one year treatment with pasireotide LAR monotherapy: dopamine agonists and growth hormone receptor antagonists (Extension full analysis set) Extension baseline up to approximately week 268
Secondary 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) The percentage of patients achieving mean growth hormone (GH) levels < 2.5 µg/L was calculated with two sided 95% confidence interval. All GH assessments were based on a 5-point mean growth hormone (GH) assessed from a 2-hour profile. Scheduled time points for blood sampling were pre-dose at 0, 30, 60, 90 and 120 minutes. Concomitant medication known to affect GH levels were allowed in patients who were not biochemically controlled after at least one year treatment with pasireotide LAR monotherapy: dopamine agonists and growth hormone receptor antagonists (Extension full analysis set) Extension baseline up to approximately week 268
Secondary 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) The percentage of patients achieving mean growth hormone (GH) levels < 1.0 µg/L and normalization of sex and age-adjusted IGF-1 was calculated with two sided 95% confidence interval. All GH assessments were based on a 5-point mean growth hormone (GH) assessed from a 2-hour profile. Scheduled time points for blood sampling were pre-dose at 0, 30, 60, 90 and 120 minutes. Total insulin-like growth factor (IGF-1) levels were assessed with one pre-dose sample at the same visits as GH. Concomitant medication known to affect GH or IGF-1 levels were allowed in patients who were not biochemically controlled after at least one year treatment with pasireotide LAR monotherapy: dopamine agonists and growth hormone receptor antagonists (Extension full analysis set Extension baseline up to approximately week 268
Secondary 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) The percentage of patients achieving mean growth hormone (GH) levels < 1.0 µg/L was calculated with two sided 95% confidence interval. All GH assessments were based on a 5-point mean growth hormone (GH) assessed from a 2-hour profile. Scheduled time points for blood sampling were pre-dose at 0, 30, 60, 90 and 120 minutes. Concomitant medication known to affect GH levels were allowed in patients who were not biochemically controlled after at least one year treatment with pasireotide LAR monotherapy: dopamine agonists and growth hormone receptor antagonists (Extension full analysis set) Extension baseline up to approximately week 268
Secondary 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) CORE baseline up to approximately 24 weeks
Secondary 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) Change from CORE baseline at each scheduled assessment was performed for patients randomized to pasireotide arms. Change from extension baseline at each scheduled assessment was performed for patients randomized to active control arm. CORE and extension baseline up to approximately 268 weeks
Secondary 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) Standardized IGF-1 = IGF-1 value / ULN, where ULN is the upper limit of the normal range CORE baseline up to approximately 24 weeks
Secondary 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) Change from CORE baseline at each scheduled assessment was performed for patients randomized to pasireotide arms. Change from extension baseline at each scheduled assessment was performed for patients randomized to active control arm. Standardized IGF-1 = IGF-1 value / ULN, where ULN is the upper limit of the normal range CORE and extension baseline up to approximately 268 weeks
Secondary 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) n is the number of patients achieving response criteria. The weeks correspond to duration of first response (in weeks) for patients achieving biomedical control. Median and 95% CI are derived from Kaplan-Meier curves. Kaplan-Meier estimates [95% CI] at each time point are estimates of probability of response. CORE baseline up to approximately 268 weeks
Secondary 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 Time to first response is defined as the time from the date of first dose to the date of first occurrence of a reduction of mean GH < 2.5 µg/L and the normalization of IGF-1. The weeks correspond to time taken to achieve first mean GH < 2.5 µg/L and the normalization of IGF-1. CORE baseline up to approximately 268 weeks
Secondary 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) Acromegaly Quality of Life questionnaire (AcroQoL) is a validated disease specific questionnaire. It contains 22 items divided into two scales: physical aspects (8 items) and psychological aspects (14 items) which is divided in two sub-scales: physical appearance and personal relationships of the patient (seven items each). The total score and sub-scores were calculated using the following formula: ((X -Y) / 4Y) x 100, X=sum of the scores for individual items (between 1 and 5 for each item), Y=number of individual items included in above sum (i.e. 22 for the total score, 8 for the physical sub-score, 14 for the psychological sub-score, 7 for the sub-score 'appearance' and 'personal relations'). The scoring of the questionnaire was performed as specified by the instrument developers. Total scores range from 0 to 100. Higher scores represent better quality of life. If more than 25% of items are not completed, results were considered invalid. CORE baseline up to approximately 24 weeks
Secondary 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) Acromegaly Quality of Life questionnaire (AcroQoL) is a validated disease specific questionnaire. It contains 22 items divided into two scales: physical aspects (8 items) and psychological aspects (14 items) which is divided in two sub-scales: physical appearance and personal relationships of the patient (seven items each). The total score and sub-scores were calculated using the following formula: ((X -Y) / 4Y) x 100, X=sum of the scores for individual items (between 1 and 5 for each item), Y=number of individual items included in above sum (i.e. 22 for the total score, 8 for the physical sub-score, 14 for the psychological sub-score, 7 for the sub-score 'appearance' and 'personal relations'). The scoring of the questionnaire was performed as specified by the instrument developers. Total scores range from 0 to 100. Higher scores represent better quality of life. If more than 25% of items are not completed, results were considered invalid. CORE Baseline and extension baseline up to approximately 268 weeks
Secondary 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) PK samples were collected for those patients treated with pasireotide LAR in the core study and who continued on pasireotide LAR in the extension phase. PK samples were collected before the injection of pasireotide LAR only at weeks 112 and 196. PK samples were also collected at weeks 48 and 132 only for all patients treated with octreotide LAR 30 mg or lanreotide ATG 120 mg in the core study who started treatment with pasireotide LAR in the extension study.
Blood samples (2.5 mL each sample) were collected to yield 1-mL plasma for analysis of pasireotide LAR oncentration.
Extension baseline up to approximately 196 weeks
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