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Trial · Interventional

CompletedPhase 3Results postedRegistry data

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

Short name PAOLA

NCTNCT01137682 (opens ClinicalTrials.gov in a new tab)Other idCSOM230C2402Other idEUDRACT 2009-016722-13
Open at ClinicalTrials.govAsk about this trial

Overview

Status
Completed
Phase
Phase 3
Enrollment
198 participants (actual)
Sponsor
Novartis Pharmaceuticals · Industry
Design
Randomized · Quadruple masking
Countries
18 countries

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

Start
19 Jul 2010
Primary completion
22 Jan 2013
Completion
28 Feb 2017
First posted
4 Jun 2010 (estimated)
Last update posted
5 Apr 2018
Conditions
Acromegaly

Timeline

1 trial · 1 completed · 1 with posted results

  • Completed
  • Ongoing
  • Not yet recruiting
  • Stopped
  • Estimated dates (est.)
  • Results posted
20102012201420162018
  1. Ph 3

    PAOLA

    NCT01137682

    19 Jul 2010 to 28 Feb 2017

Registry summary

Text and fields below are the sponsor's entries at ClinicalTrials.gov, shown as posted.

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.

Interventions

  • PasireotideDrug
  • octreotide LAR 30mgDrug
  • lanreotide ATG 120mgDrug

Arms3

  • Experimental

    Pasireotide LAR 40 mg

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

  • Experimental

    Pasireotide LAR 60 mg

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

  • Active comparator

    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.

Primary outcomes1

Outcomes the sponsor listed as primary.

  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.

    Time frame · At 24 weeks

    Registry 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.

Secondary outcomes(14)

  1. 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)

    Time frame · Extension baseline up to approximately week 268

    Registry 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)

  2. 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).

    Time frame · Extension baseline up to approximately week 268

    Registry 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)

  3. 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)

    Time frame · Extension baseline up to approximately week 268

    Registry 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)

  4. 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)

    Time frame · Extension baseline up to approximately week 268

    Registry 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

  5. 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)

    Time frame · Extension baseline up to approximately week 268

    Registry 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)

  6. 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

  7. 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)

    Time frame · CORE and extension baseline up to approximately 268 weeks

    Registry 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.

  8. 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)

    Time frame · CORE baseline up to approximately 24 weeks

    Registry description

    Standardized IGF-1 = IGF-1 value / ULN, where ULN is the upper limit of the normal range

  9. 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)

    Time frame · CORE and extension baseline up to approximately 268 weeks

    Registry 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

  10. 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)

    Time frame · CORE baseline up to approximately 268 weeks

    Registry 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.

  11. 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 frame · CORE baseline up to approximately 268 weeks

    Registry 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.

  12. 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)

    Time frame · CORE baseline up to approximately 24 weeks

    Registry 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.

  13. 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)

    Time frame · CORE Baseline and extension baseline up to approximately 268 weeks

    Registry 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.

  14. 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)

    Time frame · Extension baseline up to approximately 196 weeks

    Registry 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.

Posted results

Values are shown as posted at ClinicalTrials.gov, with their units. PepBank has not converted, pooled or compared them.

Primary outcome results

Primary outcomeNumber· At 24 weeks

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

GroupValue (percentage of participants)
Pasireotide LAR 40 mg15.4
Pasireotide LAR 60 mg20.0
Control Arm (Octreotide or Lanreotide)0
Secondary and other outcome results(7)
Secondary outcomeNumber· Extension baseline up to approximately week 268

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)

GroupValue (percentage of participants)
Pasireotide LAR 40 mg Extension19.3
Pasireotide LAR 60 mg Extension25.9
Cross Over to Pasireotide Extension19.4
Secondary outcomeNumber· 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).

GroupValue (percentage of participants)
Pasireotide LAR 40 mg Extension33.3
Pasireotide LAR 60 mg Extension29.0
Cross Over to Pasireotide Extension25.8
Secondary outcomeNumber· 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)

GroupValue (percentage of participants)
Pasireotide LAR 40 mg Extension38.6
Pasireotide LAR 60 mg Extension55.6
Control Arm (Octreotide or Lanreotide) Extension33.9
Secondary outcomeNumber· 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)

GroupValue (Participants)
Pasireotide LAR 40 mg Extension10.5
Pasireotide LAR 60 mg Extension16.7
Cross Over to Pasireotide Extension6.5
Secondary outcomeNumber· 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)

GroupValue (percentage of participants)
Pasireotide LAR 40 mg Extension14.0
Pasireotide LAR 60 mg Extension27.8
Cross Over to Pasireotide Extension8.1
Secondary outcomeMean· CORE baseline up to approximately 24 weeks

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)

GroupValue (mcg/L)Spread
Pasireotide LAR 40 mg-0.829.77
Pasireotide LAR 60 mg-6.414.35
Secondary outcomeMean· CORE and extension baseline up to approximately 268 weeks

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)

GroupValue (mcg/L)Spread
Pasireotide LAR 40 mg Extension-7.924.90
Pasireotide LAR 60 mg Extension-6.914.88
Cross Over to Pasireotide Extension-8.449.64

Adverse events, as posted

Adverse events as posted: participants affected out of participants at risk, by group
GroupDeathsSerious eventsOther events
Pasireotide LAR 40 mgPasireotide LAR 40 mg2 / 6318 / 6359 / 63
Pasireotide LAR 60 mgPasireotide LAR 60 mg0 / 6214 / 6258 / 62
Cross-over to PasireotideCross-over to pasireotide0 / 6220 / 6261 / 62

Each cell reads participants affected / participants at risk, as the registry posted them.

Registry data comes from ClinicalTrials.gov. Study results come from studies, not from the registry. How PepBank works

Studies2

Studies that cite this trial.

Studies with results

2 studies on this page

Indexing hint: Randomized controlled trial · 2020

6 results

Pasireotide for acromegaly: long-term outcomes from an extension to the Phase III PAOLA study.

Colao et al. 2020European journal of endocrinologycited by 54

PMID 32217809PMC7222286DOI 10.1530/eje-19-0762PUB-32217809

CC BY6 results
Download PDFSee results (6)

Indexing hint: Randomized controlled trial · 2014

10 results

Pasireotide versus continued treatment with octreotide or lanreotide in patients with inadequately controlled acromegaly (PAOLA): a randomised, phase 3 trial.

Gadelha et al. 2014The lancet. Diabetes & endocrinologycited by 278

PMID 25260838DOI 10.1016/s2213-8587(14)70169-xPUB-25260838

Full text at the publisher10 results
Publisher pageSee results (10)

Eligibility

Who could join, as posted.

Sex
All
Age
from 18 Years
Healthy volunteers
Not accepted
Inclusion and exclusion criteria, as posted
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

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