AcromegalyPhase 3PAOLANCT01137682
Efficacy and Safety of Pasireotide Long Acting Release (LAR) Versus Octreotide LAR or Lanreotide Autogel (ATG) in Patients With Inadequately Controlled Acromegaly
A Phase 3 study testing Pasireotide, octreotide LAR 30mg and lanreotide ATG 120mg in people with Acromegaly, run by Novartis Pharmaceuticals at 60 sites in 18 countries.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acromegaly
- What is being tested?
- Pasireotide, octreotide LAR 30mg and lanreotide ATG 120mg
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 198 participants
- Where
- 60 sitesin 18 countries
- Study dates
- 19 Jul 2010to 28 Feb 2017
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
60 sites in 18 countries.
60 sites in 18 countries
France10 sites
Novartis Investigative Site
Bron, Cedex, 69677
Novartis Investigative Site
Dijon, 21034
Novartis Investigative Site
Le Kremlin-Bicêtre, 94275
Novartis Investigative Site
Lille, 59037
Novartis Investigative Site
Marseille, 13005
Novartis Investigative Site
Paris, 75571
Novartis Investigative Site
Pessac, 33604
Novartis Investigative Site
Rennes, 35022
Novartis Investigative Site
Saint Herblain - Nantes, 44093
Novartis Investigative Site
Toulouse, Cedex 9, 31000
Brazil8 sites
Novartis Investigative Site
Botucatu, São Paulo, 18618-970
Novartis Investigative Site
Campinas, São Paulo, 13083-970
Novartis Investigative Site
Fortaleza, Ceará, 60430 370
Novartis Investigative Site
Joinville, Santa Catarina, 89201260
Novartis Investigative Site
Rio de Janeiro, Rio de Janeiro, 21941-913
Novartis Investigative Site
São Luís, Maranhão, 65020-070
Novartis Investigative Site
São Paulo, São Paulo, 04038-002
Novartis Investigative Site
São Paulo, São Paulo, 05403 000
Italy5 sites
Novartis Investigative Site
Genova, GE, 16132
Novartis Investigative Site
Messina, ME, 98125
Novartis Investigative Site
Naples, 80131
Novartis Investigative Site
Roma, RM, 00168
Novartis Investigative Site
Torino, TO, 10126
United States4 sites
University of Michigan
Ann Arbor, Michigan, 48109
University of Texas Southwestern Medical Center Division of Hematology/Oncolog
Dallas, Texas, 75235
Oregon Health & Science University
Portland, Oregon, 97239
Swedish Neuroscience Institute 550 17th Avenue, Suite 500
Seattle, Washington, 98122
Belgium4 sites
Novartis Investigative Site
Brussels, BE-B-1200
Novartis Investigative Site
Edegem, Antwerpen, 2650
Novartis Investigative Site
Ghent, 9000
Novartis Investigative Site
Leuven, 3000
Germany4 sites
Novartis Investigative Site
Erlangen, 91054
Novartis Investigative Site
Hamburg, 22587
Novartis Investigative Site
München, 80336
Novartis Investigative Site
Würzburg, 97080
Russia4 sites
Novartis Investigative Site
Barnaul, 656024
Novartis Investigative Site
Moscow, 101990
Novartis Investigative Site
Moscow, 117036
Novartis Investigative Site
Tyumen, 625023
Colombia3 sites
Novartis Investigative Site
Bogota, Cundinamarca, 111411
Novartis Investigative Site
Bogotá, 00000
Novartis Investigative Site
Cali
Poland3 sites
Novartis Investigative Site
Gdansk, 80-952
Novartis Investigative Site
Poznan, 60-355
Novartis Investigative Site
Wroclaw, 50 367
Spain3 sites
Novartis Investigative Site
Alicante, Valencia, 03010
Novartis Investigative Site
Barcelona, Catalonia, 08035
Novartis Investigative Site
Seville, Andalusia, 41013
Turkey (Türkiye)3 sites
Novartis Investigative Site
Altunizade, 34662
Novartis Investigative Site
Antalya, 07070
Novartis Investigative Site
Izmir, 35340
Norway2 sites
Novartis Investigative Site
Bergen, NO-5021
Novartis Investigative Site
Oslo, NO-0379
Saudi Arabia2 sites
Novartis Investigative Site
Jeddah, 21423
Novartis Investigative Site
Riyadh, 11211
About this study
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
This study will evaluate the efficacy and safety of pasireotide LAR 40 and 60 mg versus octreotide LAR or lanreotide ATG in patients with inadequately controlled acromegaly.
- Conditions
- Acromegaly
- Being tested
- Pasireotide, octreotide LAR 30mg, lanreotide ATG 120mg
- Keywords
- Acromegaly, hormone disorder, growth hormone, insulin like growth factor-1, pituitary tumor, pasireotide, SOM230
- Medical subject headings
- Acromegaly, Pituitary Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PasireotideDrug
Also called SOM230
- 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 30mgDrug
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 120mgDrug
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
| Study group | Role | What they receive |
|---|---|---|
| Pasireotide LAR 40 mg | Experimental | Supplied in blinded fashion as 20 and 40 mg powder in vials and 2 mL vehicle in ampoule (for reconstitution) Receives: Drug: Pasireotide |
| Pasireotide LAR 60 mg | Experimental | Supplied in blinded fashion as 20 and 40 mg powder in vials and 2 mL vehicle in ampoule (for reconstitution) Receives: Drug: Pasireotide |
| Control arm (octreotide or lanreotide) | Active comparator | If a patient is randomized to the open label arm the investigator will either:
* be instructed to contact a Novartis delegate to initiate shipment of either octreotide LAR 30 mg or lanreotide ATG 120 mg from a Novartis or designee depot to the site, or
* continue to dispense either octreotide LAR 30 mg or lanreotide ATG 120 mg available at the institution to the patient if permitted by local regulations. Receives: Drug: octreotide LAR 30mg; Drug: lanreotide ATG 120mg |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: At 24 weeks
Secondary outcomes (14)
Percentage of Patients With Mean GH < 2.5 μg/L and Normalization of IGF-1, Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly (Extension Full Analysis Set)
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)
Measured: 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).
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)
Measured: 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)
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)
Measured: 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)
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
Measured: 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)
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)
Measured: Extension baseline up to approximately week 268
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)
Measured: 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 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.
Measured: CORE and extension baseline up to approximately 268 weeks
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
Measured: CORE baseline up to approximately 24 weeks
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
Measured: CORE and extension baseline up to approximately 268 weeks
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.
Measured: CORE baseline up to approximately 268 weeks
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.
Measured: CORE baseline up to approximately 268 weeks
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.
Measured: CORE baseline up to approximately 24 weeks
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.
Measured: CORE Baseline and extension baseline up to approximately 268 weeks
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.
Measured: Extension baseline up to approximately 196 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Jun 2010 (estimated)
- Study start19 Jul 2010
- Primary completion22 Jan 2013
- Study completion28 Feb 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for AcromegalyStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 198 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01137682
- Sponsor's protocol ID
- CSOM230C2402
- Other IDs
- EUDRACT 2009-016722-13
- Acronym
- PAOLA
- Status last verified
- Apr 2018
- First submitted
- 27 May 2010
- Last updated
- 5 Apr 2018
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
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.
PubMed 32217809Gadelha 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.
PubMed 25260838
Study at a glance
From the registry record, last updated by the sponsor on 5 Apr 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01137682
- Acronym / sponsor ID
- PAOLA / CSOM230C2402
- Conditions
- Acromegaly
- Keywords
- Acromegaly, hormone disorder, growth hormone, insulin like growth factor-1, pituitary tumor, pasireotide, SOM230
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 198 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 19 Jul 2010 (actual)
- Primary completion
- 22 Jan 2013 (actual)
- Study completion
- 28 Feb 2017 (actual)
- First posted
- 4 Jun 2010 (estimated)
- Results
- Posted 21 Jan 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Pasireotide LAR 40 mg | Experimental | Drug: PasireotideSupplied in blinded fashion as 20 and 40 mg powder in vials and 2 mL vehicle in ampoule (for reconstitution) |
| Pasireotide LAR 60 mg | Experimental | Drug: PasireotideSupplied in blinded fashion as 20 and 40 mg powder in vials and 2 mL vehicle in ampoule (for reconstitution) |
| Control arm (octreotide or lanreotide) | Active comparator | Drug: octreotide LAR 30mg, Drug: lanreotide ATG 120mgIf 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (7 listed)
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PasireotideAlso: SOM230* 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 | Drug | Pasireotide LAR 40 mg, Pasireotide LAR 60 mg |
| octreotide LAR 30mgIn 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 | Drug | Control arm (octreotide or lanreotide) |
| lanreotide ATG 120mgIn 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 | Drug | Control arm (octreotide or lanreotide) |
Primary outcome
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
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.
14 secondary outcomes
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
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
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
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
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
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
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
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
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
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
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
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
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
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
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Apr 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 32217809Colao 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.
- Derived from this study: PubMed 25260838Gadelha 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.
- Individual participant dataSharing planned: Undecided
Related trials for Acromegaly
RecruitingPhase 1
A Phase 1 Clinical Trial of NTQ6179 Tablets in Healthy Volunteers
Acromegaly
RecruitingObservational study
An Observational Study of Octreotide Subcutaneous Depot in Patients With Acromegaly
Acromegaly
RecruitingPhase 3
A Study to Assess the Efficacy and Safety of Debio 4126 in Participants With Acromegaly Previously Treated With Somatostatin Analogs
Acromegaly
RecruitingObservational study
An Investigation of Pituitary Tumors and Related Hypothalmic Disorders
Panhypopituitarism, Gigantism/Acromegaly
Recruiting
Managing Pasireotide-associated Hyperglycaemia in Acromegaly With Ketogenic Diet
Acromegaly Due to Pituitary Adenoma, Hyperglycemia
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Novartis Pharmaceuticals study director
Novartis Pharmaceuticals
60 sites in 18 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Pasireotide, octreotide LAR 30mg and lanreotide ATG 120mg in people with Acromegaly, run by Novartis Pharmaceuticals at 60 sites in 18 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 5 Apr 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 60 sites in France, Brazil, Italy, United States, Belgium and 13 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 21 Jan 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01137682, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Apr 2018.