search
Back to results

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

Primary Purpose

Acromegaly

Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Pasireotide
octreotide LAR 30mg
lanreotide ATG 120mg
Sponsored by
Novartis Pharmaceuticals
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Acromegaly focused on measuring Acromegaly, hormone disorder, growth hormone, insulin like growth factor-1, pituitary tumor, pasireotide, SOM230

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • University of Michigan
  • Oregon Health & Science University
  • University of Texas Southwestern Medical Center Division of Hematology/Oncolog
  • Swedish Neuroscience Institute 550 17th Avenue, Suite 500
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Active Comparator

Arm Label

Pasireotide LAR 40 mg

Pasireotide LAR 60 mg

Control arm (octreotide or lanreotide)

Arm Description

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

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

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.

Outcomes

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.
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.

Secondary Outcome Measures

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)
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)
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)
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
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)
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)
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.
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
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
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.
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.
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.
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.
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.

Full Information

First Posted
May 27, 2010
Last Updated
April 2, 2018
Sponsor
Novartis Pharmaceuticals
search

1. Study Identification

Unique Protocol Identification Number
NCT01137682
Brief Title
Efficacy and Safety of Pasireotide Long Acting Release (LAR) Versus Octreotide LAR or Lanreotide Autogel (ATG) in Patients With Inadequately Controlled Acromegaly
Acronym
PAOLA
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
Study Type
Interventional

2. Study Status

Record Verification Date
April 2018
Overall Recruitment Status
Completed
Study Start Date
July 19, 2010 (Actual)
Primary Completion Date
January 22, 2013 (Actual)
Study Completion Date
February 28, 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novartis Pharmaceuticals

4. Oversight

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

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acromegaly
Keywords
Acromegaly, hormone disorder, growth hormone, insulin like growth factor-1, pituitary tumor, pasireotide, SOM230

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
198 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Pasireotide LAR 40 mg
Arm Type
Experimental
Arm Description
Supplied in blinded fashion as 20 and 40 mg powder in vials and 2 mL vehicle in ampoule (for reconstitution)
Arm Title
Pasireotide LAR 60 mg
Arm Type
Experimental
Arm Description
Supplied in blinded fashion as 20 and 40 mg powder in vials and 2 mL vehicle in ampoule (for reconstitution)
Arm Title
Control arm (octreotide or lanreotide)
Arm Type
Active Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Pasireotide
Other Intervention Name(s)
SOM230
Intervention Description
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
Intervention Name(s)
octreotide LAR 30mg
Intervention Description
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
Intervention Name(s)
lanreotide ATG 120mg
Intervention Description
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
Primary Outcome Measure Information:
Title
Percentage of Participants With a Reduction of Mean GH Levels to < 2.5 µg/L and Normalization of Sex- and Age-adjusted IGF-1.
Description
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.
Time Frame
At 24 weeks
Secondary Outcome Measure Information:
Title
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)
Description
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)
Time Frame
Extension baseline up to approximately week 268
Title
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).
Description
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)
Time Frame
Extension baseline up to approximately week 268
Title
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)
Description
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)
Time Frame
Extension baseline up to approximately week 268
Title
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)
Description
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
Time Frame
Extension baseline up to approximately week 268
Title
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)
Description
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)
Time Frame
Extension baseline up to approximately week 268
Title
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)
Time Frame
CORE baseline up to approximately 24 weeks
Title
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)
Description
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.
Time Frame
CORE and extension baseline up to approximately 268 weeks
Title
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)
Description
Standardized IGF-1 = IGF-1 value / ULN, where ULN is the upper limit of the normal range
Time Frame
CORE baseline up to approximately 24 weeks
Title
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)
Description
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
Time Frame
CORE and extension baseline up to approximately 268 weeks
Title
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)
Description
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.
Time Frame
CORE baseline up to approximately 268 weeks
Title
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
Description
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.
Time Frame
CORE baseline up to approximately 268 weeks
Title
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)
Description
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.
Time Frame
CORE baseline up to approximately 24 weeks
Title
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)
Description
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.
Time Frame
CORE Baseline and extension baseline up to approximately 268 weeks
Title
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)
Description
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.
Time Frame
Extension baseline up to approximately 196 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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 Exclusion Criteria: 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Novartis Pharmaceuticals
Organizational Affiliation
Novartis Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
University of Michigan
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109
Country
United States
Facility Name
Oregon Health & Science University
City
Portland
State/Province
Oregon
ZIP/Postal Code
97239
Country
United States
Facility Name
University of Texas Southwestern Medical Center Division of Hematology/Oncolog
City
Dallas
State/Province
Texas
ZIP/Postal Code
75235
Country
United States
Facility Name
Swedish Neuroscience Institute 550 17th Avenue, Suite 500
City
Seattle
State/Province
Washington
ZIP/Postal Code
98122
Country
United States
Facility Name
Novartis Investigative Site
City
Caba
State/Province
Buenos Aires
ZIP/Postal Code
C1405BCH
Country
Argentina
Facility Name
Novartis Investigative Site
City
Edegem
State/Province
Antwerpen
ZIP/Postal Code
2650
Country
Belgium
Facility Name
Novartis Investigative Site
City
Brussels
ZIP/Postal Code
BE-B-1200
Country
Belgium
Facility Name
Novartis Investigative Site
City
Gent
ZIP/Postal Code
9000
Country
Belgium
Facility Name
Novartis Investigative Site
City
Leuven
ZIP/Postal Code
3000
Country
Belgium
Facility Name
Novartis Investigative Site
City
Fortaleza
State/Province
CE
ZIP/Postal Code
60430 370
Country
Brazil
Facility Name
Novartis Investigative Site
City
Sao Luis
State/Province
MA
ZIP/Postal Code
65020-070
Country
Brazil
Facility Name
Novartis Investigative Site
City
Rio de Janeiro
State/Province
RJ
ZIP/Postal Code
21941-913
Country
Brazil
Facility Name
Novartis Investigative Site
City
Joinville
State/Province
SC
ZIP/Postal Code
89201260
Country
Brazil
Facility Name
Novartis Investigative Site
City
Botucatu
State/Province
SP
ZIP/Postal Code
18618-970
Country
Brazil
Facility Name
Novartis Investigative Site
City
Campinas
State/Province
SP
ZIP/Postal Code
13083-970
Country
Brazil
Facility Name
Novartis Investigative Site
City
Sao Paulo
State/Province
SP
ZIP/Postal Code
05403 000
Country
Brazil
Facility Name
Novartis Investigative Site
City
São Paulo
State/Province
SP
ZIP/Postal Code
04038-002
Country
Brazil
Facility Name
Novartis Investigative Site
City
Sherbrooke
State/Province
Quebec
ZIP/Postal Code
J1H 5N4
Country
Canada
Facility Name
Novartis Investigative Site
City
Bogota
State/Province
Cundinamarca
ZIP/Postal Code
111411
Country
Colombia
Facility Name
Novartis Investigative Site
City
Bogotá
ZIP/Postal Code
00000
Country
Colombia
Facility Name
Novartis Investigative Site
City
Cali
Country
Colombia
Facility Name
Novartis Investigative Site
City
Toulouse
State/Province
Cedex 9
ZIP/Postal Code
31000
Country
France
Facility Name
Novartis Investigative Site
City
Bron
State/Province
Cedex
ZIP/Postal Code
69677
Country
France
Facility Name
Novartis Investigative Site
City
Dijon
ZIP/Postal Code
21034
Country
France
Facility Name
Novartis Investigative Site
City
Le Kremlin Bicetre
ZIP/Postal Code
94275
Country
France
Facility Name
Novartis Investigative Site
City
Lille
ZIP/Postal Code
59037
Country
France
Facility Name
Novartis Investigative Site
City
Marseille
ZIP/Postal Code
13005
Country
France
Facility Name
Novartis Investigative Site
City
Paris
ZIP/Postal Code
75571
Country
France
Facility Name
Novartis Investigative Site
City
Pessac Cedex
ZIP/Postal Code
33604
Country
France
Facility Name
Novartis Investigative Site
City
Rennes Cedex
ZIP/Postal Code
35022
Country
France
Facility Name
Novartis Investigative Site
City
Saint Herblain - Nantes
ZIP/Postal Code
44093
Country
France
Facility Name
Novartis Investigative Site
City
Erlangen
ZIP/Postal Code
91054
Country
Germany
Facility Name
Novartis Investigative Site
City
Hamburg
ZIP/Postal Code
22587
Country
Germany
Facility Name
Novartis Investigative Site
City
Muenchen
ZIP/Postal Code
80336
Country
Germany
Facility Name
Novartis Investigative Site
City
Wurzburg
ZIP/Postal Code
97080
Country
Germany
Facility Name
Novartis Investigative Site
City
Petach Tikva
ZIP/Postal Code
49100
Country
Israel
Facility Name
Novartis Investigative Site
City
Genova
State/Province
GE
ZIP/Postal Code
16132
Country
Italy
Facility Name
Novartis Investigative Site
City
Messina
State/Province
ME
ZIP/Postal Code
98125
Country
Italy
Facility Name
Novartis Investigative Site
City
Roma
State/Province
RM
ZIP/Postal Code
00168
Country
Italy
Facility Name
Novartis Investigative Site
City
Torino
State/Province
TO
ZIP/Postal Code
10126
Country
Italy
Facility Name
Novartis Investigative Site
City
Napoli
ZIP/Postal Code
80131
Country
Italy
Facility Name
Novartis Investigative Site
City
Bergen
ZIP/Postal Code
NO-5021
Country
Norway
Facility Name
Novartis Investigative Site
City
Oslo
ZIP/Postal Code
NO-0379
Country
Norway
Facility Name
Novartis Investigative Site
City
Gdansk
ZIP/Postal Code
80-952
Country
Poland
Facility Name
Novartis Investigative Site
City
Poznan
ZIP/Postal Code
60-355
Country
Poland
Facility Name
Novartis Investigative Site
City
Wroclaw
ZIP/Postal Code
50 367
Country
Poland
Facility Name
Novartis Investigative Site
City
Bucuresti
ZIP/Postal Code
011863
Country
Romania
Facility Name
Novartis Investigative Site
City
Barnaul
ZIP/Postal Code
656024
Country
Russian Federation
Facility Name
Novartis Investigative Site
City
Moscow
ZIP/Postal Code
101990
Country
Russian Federation
Facility Name
Novartis Investigative Site
City
Moscow
ZIP/Postal Code
117036
Country
Russian Federation
Facility Name
Novartis Investigative Site
City
Tyumen
ZIP/Postal Code
625023
Country
Russian Federation
Facility Name
Novartis Investigative Site
City
Jeddah
ZIP/Postal Code
21423
Country
Saudi Arabia
Facility Name
Novartis Investigative Site
City
Riyadh
ZIP/Postal Code
11211
Country
Saudi Arabia
Facility Name
Novartis Investigative Site
City
Sevilla
State/Province
Andalucia
ZIP/Postal Code
41013
Country
Spain
Facility Name
Novartis Investigative Site
City
Barcelona
State/Province
Catalunya
ZIP/Postal Code
08035
Country
Spain
Facility Name
Novartis Investigative Site
City
Alicante
State/Province
Comunidad Valenciana
ZIP/Postal Code
03010
Country
Spain
Facility Name
Novartis Investigative Site
City
Altunizade
ZIP/Postal Code
34662
Country
Turkey
Facility Name
Novartis Investigative Site
City
Antalya
ZIP/Postal Code
07070
Country
Turkey
Facility Name
Novartis Investigative Site
City
Izmir
ZIP/Postal Code
35340
Country
Turkey
Facility Name
Novartis Investigative Site
City
Plymouth
ZIP/Postal Code
PL6 8DH
Country
United Kingdom

12. IPD Sharing Statement

Plan to Share IPD
Undecided
Citations:
PubMed Identifier
32217809
Citation
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.
Results Reference
derived
PubMed Identifier
25260838
Citation
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.
Results Reference
derived

Learn more about this trial

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

We'll reach out to this number within 24 hrs