AcromegalyPhase 3NCT00600886
Safety and Efficacy of Pasireotide Long Acting Release (LAR) vs. Octreotide LAR in Patients With Active Acromegaly
A Phase 3 study testing Pasireotide and Octreotide in people with Acromegaly, run by Novartis Pharmaceuticals at 95 sites in 27 countries.
Trial summary
The patients received either Pasireotide LAR or Octreotide LAR for one year of treatment. The objective of this study was to compare the proportion of patients with a reduction of mean GH level to <2.5 µg/L and the normalization of IGF-1 to within normal limits (age and sex related) between the two treatment groups… 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 and Octreotide
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 358 participants
- Where
- 95 sitesin 27 countries
- Study dates
- 11 Feb 2008to 11 Mar 2016
- 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 active acromegaly (based on elevated GH and IGF-1 levels)
- Patients who have undergone one or more pituitary surgeries, but have not been treated medically, or de-novo patients presenting a visible pituitary adenoma on MRI and who refuse pituitary surgery or for whom pituitary surgery is contraindicated
- Patients for whom written informed consent to participate in the study has been obtained prior to any study related activity
Who cannot join
- Patients who are being or were treated with octreotide, lanreotide, dopamine agonists or GH antagonists with the exception of a single dose of short-acting octrotide or short-acting dopamine agonists. In case of a single dose of short-acting octrotide, the dose should not be used to predict the response to the octretide treatment. The single dose of short-acting octreotide or short-acting dopamine agonists should not be administered in the 3 days prior to randomization
- Patients with compression of the optic chiasm causing any visual field defect
- Patients who have received pituitary irradiation within the last ten years prior to visit 1
- Poorly controlled diabetic patients
- Other protocol-defined inclusion/exclusion criteria may apply
Trial locations and contacts
95 sites in 27 countries.
95 sites in 27 countries
United States14 sites
University of Michigan Comprehensive Cancer Center Deptof Endocrinology&Diabetes
Ann Arbor, Michigan, 48109-0944
Johns Hopkins University School of Medicine Dept.ofJohnsHopkinsUniv.
Baltimore, Maryland, 21205
University of Texas Southwestern Medical Center Danziger Research Bldg.
Dallas, Texas, 75390
University of Florida SC
Gainesville, Florida, 32610
University of Texas/MD Anderson Cancer Center Regulatory -12
Houston, Texas, 77030-4009
Baylor College of Medicine
Houston, Texas, 77030
Cedars Sinai Medical Center The Pituitary Center
Los Angeles, California, 90048
University of California at Los Angeles Division of Endocrinology
Los Angeles, California, 90095
Columbia University Medical Center- New York Presbyterian Dept. of CU Collegeof Phys&Sur
New York, New York, 10032
Northport VA Medical Center CSOM230C2305
Northport, New York, 11768
Allegheny Endocrinology Associates
Pittsburgh, Pennsylvania, 15212
Oregon Health & Sciences University DeptofOregonHealth&Sciences(3)
Portland, Oregon, 97201
Swedish Medical Center Dept.ofSeattle Neuroscience(2)
Seattle, Washington
Stanford University Medical Center Stanford Cancer Center (3)
Stanford, California, 94304
France7 sites
Novartis Investigative Site
Bois-Guillaume, 76233
Novartis Investigative Site
Bron, 69677
Novartis Investigative Site
Le Kremlin-Bicêtre, 94275
Novartis Investigative Site
Marseille, 13385
Novartis Investigative Site
Montpellier, 34295
Novartis Investigative Site
Paris, 75014
Novartis Investigative Site
Pessac, 33604
Italy7 sites
Novartis Investigative Site
Cona, FE, 44100
Novartis Investigative Site
Genova, GE, 16132
Novartis Investigative Site
Naples, 80131
Novartis Investigative Site
Padova, PD, 35128
Novartis Investigative Site
Pisa, PI, 56124
Novartis Investigative Site
Roma, RM, 00168
Novartis Investigative Site
Torino, TO, 10126
Brazil6 sites
Novartis Investigative Site
Brasília, Federal District, 70840-901
Novartis Investigative Site
Curitiba, Paraná, 80060-900
Novartis Investigative Site
Fortaleza, Ceará, 60430 370
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, 05403-000
Canada5 sites
Novartis Investigative Site
Edmonton, Alberta, T6G 2B7
Novartis Investigative Site
Halifax, Nova Scotia, B3H 2Y9
Novartis Investigative Site
Montreal, Quebec, H2L 2W5
Novartis Investigative Site
Sherbrooke, Quebec, J1H 5N4
Novartis Investigative Site
Vancouver, British Columbia, V5Z 1M9
Germany5 sites
Novartis Investigative Site
Berlin, 10098
Novartis Investigative Site
Berlin, 12203
Novartis Investigative Site
Erlangen, 91054
Novartis Investigative Site
Essen, 45122
Novartis Investigative Site
München, 80336
Belgium4 sites
Novartis Investigative Site
Brussels, 1070
Novartis Investigative Site
Brussels, 1090
Novartis Investigative Site
Ghent, 9000
Novartis Investigative Site
Leuven, 3000
Russia4 sites
Novartis Investigative Site
Moscow, 117036
Novartis Investigative Site
Moscow, 119992
Novartis Investigative Site
Saint Petersburg, 194044
Novartis Investigative Site
Saint Petersburg, 197341
South Korea4 sites
Novartis Investigative Site
Seoul, Korea, 03722
Novartis Investigative Site
Seoul, Korea, 05505
Novartis Investigative Site
Seoul, Korea, 06351
Novartis Investigative Site
Seoul, 130-872
Spain4 sites
Novartis Investigative Site
Alicante, Valencia, 03010
Novartis Investigative Site
L'Hospitalet de Llobregat, Barcelona, 08907
Novartis Investigative Site
Santiago de Compostela, Galicia, 15706
Novartis Investigative Site
Seville, Andalusia, 41013
United Kingdom4 sites
Novartis Investigative Site
Leeds, LS1 3EX
Novartis Investigative Site
Liverpool, L7 8XP
Novartis Investigative Site
London, EC1A 7BE
Novartis Investigative Site
Southampton, SO16 6YD
Argentina3 sites
Novartis Investigative Site
Buenos Aires, C1232AAC
Novartis Investigative Site
CABA, Buenos Aires, C1405BCH
Novartis Investigative Site
Capital Federal, Buenos Aires, 1425EKP
Sweden3 sites
Novartis Investigative Site
Linköping, SE-581 85
Novartis Investigative Site
Malmö, SE-205 02
Novartis Investigative Site
Uppsala, SE-751 85
Taiwan3 sites
Novartis Investigative Site
Linkou District, 33305
Novartis Investigative Site
Taichung, 40705
Novartis Investigative Site
Taipei, 10002
China2 sites
Novartis Investigative Site
Beijing, Beijing Municipality, 100730
Novartis Investigative Site
Shanghai, 200025
Denmark2 sites
Novartis Investigative Site
Aalborg, DK-9100
Novartis Investigative Site
Copenhagen, DK-2100
Greece2 sites
Novartis Investigative Site
Athens, GR, 115 27
Novartis Investigative Site
Piraeus, 18537
Israel2 sites
Novartis Investigative Site
Jerusalem, 91120
Novartis Investigative Site
Petah Tikva, 49100
Mexico2 sites
Novartis Investigative Site
Mexico City, Mexico City, 06720
Novartis Investigative Site
Mexico City, Mexico City, 06726
Netherlands2 sites
Novartis Investigative Site
Nijmegen, 6525 GA
Novartis Investigative Site
Rotterdam, 3015 CE
Norway2 sites
Novartis Investigative Site
Bergen, NO-5021
Novartis Investigative Site
Oslo, NO-0379
Poland2 sites
Novartis Investigative Site
Krakow, 31-531
Novartis Investigative Site
Warsaw, 01 809
Turkey (Türkiye)2 sites
Novartis Investigative Site
Ankara, 06100
Novartis Investigative Site
Erzurum, 25240
About this study
Official title: A Multicenter, Randomized, Blinded Study to Assess Safety and Efficacy of Pasireotide LAR vs. Octreotide LAR in Patients With Active Acromegaly
The patients received either Pasireotide LAR or Octreotide LAR for one year of treatment.
The objective of this study was to compare the proportion of patients with a reduction of mean GH level to <2.5 µg/L and the normalization of IGF-1 to within normal limits (age and sex related) between the two treatment groups (pasireotide LAR and octreotide LAR) at 12 months.
Following one year of treatment patients could proceed into the study extension.
Patients who did not respond to the treatment they were randomized to (based on month 12 assessment results) were switched to the other treatment arm at month 13.
- Conditions
- Acromegaly
- Being tested
- Pasireotide, Octreotide
- Keywords
- Acromegaly,, adult,, growth hormone,, insulin-like growth factor I,, somatostatin analogue
- Medical subject headings
- Acromegaly
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PasireotideDrug
Also called SOM230
Pasireotide LAR - intramuscular (i.m.) depot injection given once every 28 days.
OctreotideDrug
Octreotide LAR - i.m. depot injection given once every 28 days.
| Study group | Role | What they receive |
|---|---|---|
| Pasireotide LAR | Experimental | Patients in this arm received Pasireotide LAR 40 mg im depot injection, blinded, once every 28 days (± 2 days) for 12 months. Dose could be down- or up-titrated to 20 or 60 mg, respectively. Patients who responded to Pasireotide LAR (i.e. the randomized treatment) at the end of the core (Month 12), continued Pasireotide LAR treatment in the extension. Patients who did not respond to Pasireotide LAR at the end of the core (Month 12) were allowed to switch to receive Octreotide LAR in the extension. Receives: Drug: Pasireotide |
| Octreotide LAR | Active comparator | Patients in this arm received Octreotide LAR 20 mg im depot injection, blinded, once every 28 days (± 2 days) for 12 months. Dose could be down- or up-titrated to 10 or 30 mg, respectively. Patients who responded to Octreotide LAR (i.e. the randomized treatment) at the end of the core (Month 12) continued Octreotide LAR treatment in the extension (up to 2 years of treatment). Patients who did not respond to Octreotide LAR at the end of the core (Month 12) were allowed to switch to receive Pasireotide LAR in the extension. Receives: Drug: Octreotide |
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 Level to <2.5 μg/L and the Normalization of IGF-1
Percentage of participants with a reduction of mean GH levels to <2.5μg/L (based on a 5-point 2-hour profile) and normalization of sex- and age-adjusted IGF-1.
Post surgery = patients with prior surgery but no previous medical treatment for acromegaly De novo = patients with de novo disease who refused pituitary surgery or for whom pituitary surgery was contraindicated.
Measured: 12 months
Secondary outcomes (25)
Percentage of Participants With a Reduction of Mean GH Level to < 2.5μg/L
Percentage of participants with a reduction of mean GH levels to < 2.5μg/L (based on a 5-point 2-hour profile).
Post surgery = patients with prior surgery but no previous medical treatment for acromegaly De novo = patients with de novo disease who refused pituitary surgery or for whom pituitary surgery was contraindicated.
Measured: 12 Months
Change From Baseline in Tumor Volume at 12 Months
Absolute and percentage change from baseline in tumor volume (assessed by pituitary MRI) Post surgery = patients with prior surgery but no previous medical treatment for acromegaly De novo = patients with de novo disease who refused pituitary surgery or for whom pituitary surgery was contraindicated.
Measured: Baseline, 12 Months
Percentage of Participants With Normalization of IGF-1
Percentage of participants with normalization of sex- and age-adjusted IGF-1. Post surgery = patients with prior surgery but no previous medical treatment for acromegaly De novo = patients with de novo disease who refused pituitary surgery or for whom pituitary surgery was contraindicated.
Measured: 12 Months
Percentage of Participants With a Reduction of Mean GH Level to < 2.5μg/L and Normalization of IGF-1
Percentage of participants with a reduction of mean GH levels to < 2.5μg/L (based on a 5-point 2-hour profile) and normalization of sex- and age-adjusted IGF-1.
Denominator for time points up to Month 12 is the Full Analysis Set (FAS). Denominator for time points after Month 12 excludes patients who completed the core and did not enter the extension. Patients who discontinued were considered non-responders for the time points after discontinuation, patients who crossed over were considered non-responders for all time points after crossover. Analysis was based on data up to crossover (i.e., included data from both blinded core \& ext. phase up to 26 Months for patients who continued the same treatment in the extension. For patients who switched to the other treatment, only data collected before crossover was included.)
Measured: Months 3, 6, 9, 12, 16, 19, 22, 25
Summary of Mean GH Values
Mean GH levels (based on a 5-point profile over 2 hours). Analysis was based on data up to crossover (i.e., included data from both blinded core and extension phase up to 26 Months for patients who continued the same treatment in the extension. For patients who switched to the other treatment, only data collected before crossover was included).
Measured: Baseline, Months 3, 6, 9, 12, 16, 19, 22, 25
Time to First Response for Patients Achieving a Reduction of Mean GH Level to < 2.5 μg/L and Normalization of IGF-1 (No. of Responders: Pasireotite LAR = 81, Octreotide LAR = 63) )
Time to first response for patients achieving a reduction of mean GH level to < 2.5 μg/L and normalization of IGF-1. Analysis was based on data up to crossover (i.e., included data from both blinded core and extension phase up to 26 Months for patients who continued the same treatment in the extension. For patients who switched to the other treatment, only data collected before crossover was included).
Measured: Up to 26 months
Severity Scores of Acromegaly Symptoms
Severity scores of acromegaly symptoms (Headache, Fatigue, Perspiration, Paresthesias, Osteoarthralgia). Symptoms were scored from 0 (no symptom) to 4 (very severe). Analysis was based on data up to crossover (i.e., included data from both blinded core and extension phase up to 26 Months for patients who continued the same treatment in the extension. For patients who switched to the other treatment, only data collected before crossover was included).
Measured: Baseline, Months 12, 25
Ring Size
Ring size (based on jeweler's finger gauge). Analysis was based on data up to crossover (i.e., included data from both blinded core and extension phase up to 26 Months for patients who continued the same treatment in the extension. For patients who switched to the other treatment, only data collected before crossover was included).
Measured: Baseline, Months 12, 25
Health-related Quality-of-life as Measured by the AcroQoL Questionnaire
Acromegalyy quality of life (AcroQoL) total scores. The AcroQoL questionnaire is unidimensional and contains 22 items divided in two scales: one that evaluates physical aspects (eight items) and another one that evaluates psychological aspects (14 items). 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. Analysis was based on data up to crossover (i.e., included data from both blinded core and extension phase up to 26 Months for patients who continued the same treatment in the extension. For patients who switched to the other treatment, only data collected before crossover was included).
Measured: Baseline, Months 12, 25
Summary of Prolactin Levels
Prolactin Levels. Analysis was based on data up to crossover (i.e., included data from both blinded core and extension phase up to 26 Months for patients who continued the same treatment in the extension. For patients who switched to the other treatment, only data collected before crossover was included).
Measured: Baseline, Months 12, 25
Duration of Response for Patients Achieving a Reduction of Mean GH Level to <2.5 μg/L and the Normalization of IGF-1 at Month 12 (No. of Responders: Pasireotide LAR = 51, Octreotide LAR = 32)
The duration of response is defined as the time from the date that patient first met and maintained the response criteria based on primary efficacy variable to the date that patient lost response status.
Median and corresponding 95% CI are derived based on Kaplan-Meier method. Analysis was based on data up to crossover (i.e., included data from both blinded core and extension phase up to 26 Months for patients who continued the same treatment in the extension. For patients who switched to the other treatment, only data collected before crossover was included).
Measured: Up to 26 months
Pasireotide Trough Concentrations by Incident Dose
Pasireotide LAR trough concentrations by incident dose (last dose administered prior to PK sample collection). PK observations with missing concentrations, missing dose, missing elapsed time or an elapsed time from previous injection outside of 28±2 days window were excluded.
5 patients with evaluable PK data in the pasireotide arm received erroneously 20 mg pasireotide LAR at baseline.
Measured: Months 1 - 12
Octreotide Trough Concentrations by Incident Dose
Octreotide LAR trough concentrations by incident dose (last dose administered prior to PK sample collection). PK observations with missing concentrations, missing dose, missing elapsed time or an elapsed time from previous injection outside of 28±2 days window were excluded.
Measured: Months 1 - 12
Percentage of Participants With a Reduction of Mean GH Level to < 2.5μg/L and Normalization of IGF-1 After Crossover
Percentage of participants with a reduction of mean GH levels to < 2.5μg/L (based on a 5-point 2-hour profile) and normalization of sex- and age-adjusted IGF-1. Analysis was based on data after crossover (i.e., included data from blinded extension phase collected after the crossover time point for patients who crossed over). Denominator for all time points is the Crossover Analysis Set (CAS).
Measured: Months 3, 6, 9, 12 after crossover
Percentage of Participants With a Reduction of Mean GH Level to < 2.5μg/L
Percentage of participants with a reduction of mean GH levels to < 2.5μg/L (based on a 5-point 2-hour profile).
Analysis was based on data up to crossover (i.e., included data from both blinded core and extension phase up to 26 Months for patients who continued the same treatment in the extension. For patients who switched to the other treatment, only data collected before crossover was included). Denominator for time points up to Month 12 is the Full Analysis Set. Denominator for time points after Month 12 excludes patients who completed the core and did not enter the extension. Patients who discontinued were considered non-responders for the time points after discontinuation, patients who crossed over were considered non-responders for all time points after crossover.
Measured: Months 3, 6, 9, 12, 16, 19, 22, 25
Percentage of Participants With Normalization of IGF-1
Percentage of participants with normalization of sex- and age-adjusted IGF-1. Analysis was based on data up to crossover (i.e., included data from both blinded core and extension phase up to 26 Months for patients who continued the same treatment in the extension. For patients who switched to the other treatment, only data collected before crossover was included). Denominator for time points up to Month 12 is the FAS. Denominator for time points after Month 12 excludes patients who completed the core and did not enter the extension. Patients who discontinued were considered non-responders for the time points after discontinuation, patients who crossed over were considered non-responders for all time points after crossover.
Measured: Months 3, 6, 9, 12, 16, 19, 22, 25
Change From Baseline in Tumor Volume
Percentage change from baseline in tumor volume (assessed by pituitary MRI). Analysis was based on data up to crossover (i.e., included data from both blinded core and extension phase up to 26 Months for patients who continued the same treatment in the extension. For patients who switched to the other treatment, only data collected before crossover was included).
Measured: Baseline, months 6, 12, 19, 25
Percentage of Participants With a Reduction of Mean GH Level to < 2.5μg/L After Crossover
Percentage of participants with a reduction of mean GH levels to < 2.5μg/L (based on a 5-point 2-hour profile). Analysis was based on data after crossover (i.e., included data from blinded extension phase collected after the crossover time point for patients who crossed over). Denominator for all time points is the Crossover Analysis Set (CAS).
Measured: Months 3, 6, 9, 12 after crossover
Percentage of Participants With Normalization of IGF-1 After Crossover
Percentage of participants with normalization of sex- and age-adjusted IGF-1. Analysis was based on data after crossover (i.e., included data from blinded extension phase collected after the crossover time point for patients who crossed over). Denominator for all time points is the Crossover Analysis Set (CAS).
Measured: Months 3, 6, 9, 12 after crossover
Summary of Mean GH Values After Crossover
Mean GH levels (based on a 5-point profile over 2 hours). Extension baseline was defined as last measurement prior to the start of crossover treatment. Analysis was based on data after crossover (i.e., included data from blinded extension phase collected after the crossover time point for patients who crossed over).
Measured: Extension baseline, months 3, 6, 9, 12 after crossover
Change From Extension Baseline in Tumor Volume After Crossover
Percentage change from extension baseline in tumor volume (assessed by pituitary MRI).
Extension baseline was defined as last assessment prior to the administration of the new treatment after crossover. Analysis was based on data after crossover (i.e., included data from blinded extension phase collected after the crossover time point for patients who crossed over).
Measured: Extension baseline, months 6, 12 after crossover
Severity Scores of Acromegaly Symptoms After Crossover
Severity scores of acromegaly symptoms (Headache, Fatigue, Perspiration, Paresthesias, Osteoarthralgia).
Symptoms were scored from 0 (no symptom) to 4 (very severe). Extension baseline was defined as last measurement prior to the start of crossover treatment. Analysis was based on data after crossover (i.e., included data from blinded extension phase collected after the crossover time point for patients who crossed over).
Measured: Extension baseline, month 12 after crossover
Ring Size After Crossover
Ring size (based on jeweler's finger gauge). Extension baseline was defined as last measurement prior to the start of crossover treatment. Analysis was based on data after crossover (i.e., included data from blinded extension phase collected after the crossover time point for patients who crossed over). BL = baseline, LH = left hand, RH = right hand, CO = crossover
Measured: Extension baseline, month 12 after crossover
Health-related Quality-of-life as Measured by the AcroQoL Questionnaire After Crossover
AcroQoL total scores. The AcroQoL questionnaire is unidimensional and contains 22 items divided in two scales: one that evaluates physical aspects (eight items) and another one that evaluates psychological aspects (14 items). The scoring of the questionnaire was performed as specified by the instrument developers. Extension baseline was defined as last measurement prior to the start of crossover treatment. Analysis was based on data after crossover (i.e., included data from blinded extension phase collected after the crossover time point for patients who crossed over). Total scores range from 0 to 100. Higher scores represent better quality of life.
Measured: Extension baseline, months 12 after crossover
Summary of Prolactin Levels After Crossover
Prolactin (PRL) levels. Analysis was based on data after crossover (i.e., included data from blinded extension phase collected after the crossover time point for patients who crossed over). Extension baseline was defined as last measurement prior to the start of crossover treatment.
Measured: Extension baseline, month 12 after crossover
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Jan 2008 (estimated)
- Study start11 Feb 2008
- Primary completion11 Mar 2016
- Study completion11 Mar 2016
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 (3)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
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 358 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis PharmaceuticalsNovartis, Study chair, Novartis
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00600886
- Sponsor's protocol ID
- CSOM230C2305
- Other IDs
- 2007-001972-36
- Status last verified
- Jun 2017
- First submitted
- 14 Jan 2008
- Last updated
- 2 Jul 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Bronstein MD, Fleseriu M, Neggers S, Colao A, Sheppard M, Gu F, Shen CC, Gadelha M, Farrall AJ, Hermosillo Resendiz K, Ruffin M, Chen Y, Freda P; Pasireotide C2305 Study Group. Switching patients with acromegaly from octreotide to pasireotide improves biochemical control: crossover extension to a randomized, double-blind, Phase III study. BMC Endocr Disord. 2016 Apr 2;16:16. doi: 10.1186/s12902-016-0096-8.
PubMed 27039081Shanik MH, Cao PD, Ludlam WH. HISTORICAL RESPONSE RATES OF SOMATOSTATIN ANALOGUES IN THE TREATMENT OF ACROMEGALY: A SYSTEMATIC REVIEW. Endocr Pract. 2016 Mar;22(3):350-6. doi: 10.4158/EP15913.RA. Epub 2015 Oct 5.
PubMed 26437217Sheppard M, Bronstein MD, Freda P, Serri O, De Marinis L, Naves L, Rozhinskaya L, Hermosillo Resendiz K, Ruffin M, Chen Y, Colao A. Pasireotide LAR maintains inhibition of GH and IGF-1 in patients with acromegaly for up to 25 months: results from the blinded extension phase of a randomized, double-blind, multicenter, Phase III study. Pituitary. 2015 Jun;18(3):385-94. doi: 10.1007/s11102-014-0585-6.
PubMed 25103549
Study at a glance
From the registry record, last updated by the sponsor on 2 Jul 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicenter, Randomized, Blinded Study to Assess Safety and Efficacy of Pasireotide LAR vs. Octreotide LAR in Patients With Active Acromegaly
- ClinicalTrials.gov ID
- NCT00600886
- Acronym / sponsor ID
- CSOM230C2305
- Conditions
- Acromegaly
- Keywords
- Acromegaly,, adult,, growth hormone,, insulin-like growth factor I,, somatostatin analogue
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 358 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 11 Feb 2008 (actual)
- Primary completion
- 11 Mar 2016 (actual)
- Study completion
- 11 Mar 2016 (actual)
- First posted
- 25 Jan 2008 (estimated)
- Results
- Posted 30 Jan 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The patients received either Pasireotide LAR or Octreotide LAR for one year of treatment.
The objective of this study was to compare the proportion of patients with a reduction of mean GH level to <2.5 µg/L and the normalization of IGF-1 to within normal limits (age and sex related) between the two treatment groups (pasireotide LAR and octreotide LAR) at 12 months.
Following one year of treatment patients could proceed into the study extension.
Patients who did not respond to the treatment they were randomized to (based on month 12 assessment results) were switched to the other treatment arm at month 13.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Pasireotide LAR | Experimental | Drug: PasireotidePatients in this arm received Pasireotide LAR 40 mg im depot injection, blinded, once every 28 days (± 2 days) for 12 months. Dose could be down- or up-titrated to 20 or 60 mg, respectively. Patients who responded to Pasireotide LAR (i.e. the randomized treatment) at the end of the core (Month 12), continued Pasireotide LAR treatment in the extension. Patients who did not respond to Pasireotide LAR at the end of the core (Month 12) were allowed to switch to receive Octreotide LAR in the extension. |
| Octreotide LAR | Active comparator | Drug: OctreotidePatients in this arm received Octreotide LAR 20 mg im depot injection, blinded, once every 28 days (± 2 days) for 12 months. Dose could be down- or up-titrated to 10 or 30 mg, respectively. Patients who responded to Octreotide LAR (i.e. the randomized treatment) at the end of the core (Month 12) continued Octreotide LAR treatment in the extension (up to 2 years of treatment). Patients who did not respond to Octreotide LAR at the end of the core (Month 12) were allowed to switch to receive Pasireotide LAR in the extension. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Patients with active acromegaly (based on elevated GH and IGF-1 levels)
- Patients who have undergone one or more pituitary surgeries, but have not been treated medically, or de-novo patients presenting a visible pituitary adenoma on MRI and who refuse pituitary surgery or for whom pituitary surgery is contraindicated
- Patients for whom written informed consent to participate in the study has been obtained prior to any study related activity
Key exclusion criteria (5 listed)
- Patients who are being or were treated with octreotide, lanreotide, dopamine agonists or GH antagonists with the exception of a single dose of short-acting octrotide or short-acting dopamine agonists. In case of a single dose of short-acting octrotide, the dose should not be used to predict the response to the octretide treatment. The single dose of short-acting octreotide or short-acting dopamine agonists should not be administered in the 3 days prior to randomization
- Patients with compression of the optic chiasm causing any visual field defect
- Patients who have received pituitary irradiation within the last ten years prior to visit 1
- Poorly controlled diabetic patients
- Other protocol-defined inclusion/exclusion criteria may apply
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: SOM230Pasireotide LAR - intramuscular (i.m.) depot injection given once every 28 days. | Drug | Pasireotide LAR |
| OctreotideOctreotide LAR - i.m. depot injection given once every 28 days. | Drug | Octreotide LAR |
Primary outcome
Percentage of Participants With a Reduction of Mean GH Level to <2.5 μg/L and the Normalization of IGF-1
Time frame: 12 months
Percentage of participants with a reduction of mean GH levels to <2.5μg/L (based on a 5-point 2-hour profile) and normalization of sex- and age-adjusted IGF-1. Post surgery = patients with prior surgery but no previous medical treatment for acromegaly De novo = patients with de novo disease who refused pituitary surgery or for whom pituitary surgery was contraindicated.
25 secondary outcomes
Percentage of Participants With a Reduction of Mean GH Level to < 2.5μg/L
Time frame: 12 Months
Change From Baseline in Tumor Volume at 12 Months
Time frame: Baseline, 12 Months
Percentage of Participants With Normalization of IGF-1
Time frame: 12 Months
Percentage of Participants With a Reduction of Mean GH Level to < 2.5μg/L and Normalization of IGF-1
Time frame: Months 3, 6, 9, 12, 16, 19, 22, 25
Summary of Mean GH Values
Time frame: Baseline, Months 3, 6, 9, 12, 16, 19, 22, 25
Time to First Response for Patients Achieving a Reduction of Mean GH Level to < 2.5 μg/L and Normalization of IGF-1 (No. of Responders: Pasireotite LAR = 81, Octreotide LAR = 63) )
Time frame: Up to 26 months
Severity Scores of Acromegaly Symptoms
Time frame: Baseline, Months 12, 25
Ring Size
Time frame: Baseline, Months 12, 25
Health-related Quality-of-life as Measured by the AcroQoL Questionnaire
Time frame: Baseline, Months 12, 25
Summary of Prolactin Levels
Time frame: Baseline, Months 12, 25
Duration of Response for Patients Achieving a Reduction of Mean GH Level to <2.5 μg/L and the Normalization of IGF-1 at Month 12 (No. of Responders: Pasireotide LAR = 51, Octreotide LAR = 32)
Time frame: Up to 26 months
Pasireotide Trough Concentrations by Incident Dose
Time frame: Months 1 - 12
Octreotide Trough Concentrations by Incident Dose
Time frame: Months 1 - 12
Percentage of Participants With a Reduction of Mean GH Level to < 2.5μg/L and Normalization of IGF-1 After Crossover
Time frame: Months 3, 6, 9, 12 after crossover
Percentage of Participants With a Reduction of Mean GH Level to < 2.5μg/L
Time frame: Months 3, 6, 9, 12, 16, 19, 22, 25
Percentage of Participants With Normalization of IGF-1
Time frame: Months 3, 6, 9, 12, 16, 19, 22, 25
Change From Baseline in Tumor Volume
Time frame: Baseline, months 6, 12, 19, 25
Percentage of Participants With a Reduction of Mean GH Level to < 2.5μg/L After Crossover
Time frame: Months 3, 6, 9, 12 after crossover
Percentage of Participants With Normalization of IGF-1 After Crossover
Time frame: Months 3, 6, 9, 12 after crossover
Summary of Mean GH Values After Crossover
Time frame: Extension baseline, months 3, 6, 9, 12 after crossover
Change From Extension Baseline in Tumor Volume After Crossover
Time frame: Extension baseline, months 6, 12 after crossover
Severity Scores of Acromegaly Symptoms After Crossover
Time frame: Extension baseline, month 12 after crossover
Ring Size After Crossover
Time frame: Extension baseline, month 12 after crossover
Health-related Quality-of-life as Measured by the AcroQoL Questionnaire After Crossover
Time frame: Extension baseline, months 12 after crossover
Summary of Prolactin Levels After Crossover
Time frame: Extension baseline, month 12 after crossover
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Jul 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 27039081Bronstein MD, Fleseriu M, Neggers S, Colao A, Sheppard M, Gu F, Shen CC, Gadelha M, Farrall AJ, Hermosillo Resendiz K, Ruffin M, Chen Y, Freda P; Pasireotide C2305 Study Group. Switching patients with acromegaly from octreotide to pasireotide improves biochemical control: crossover extension to a randomized, double-blind, Phase III study. BMC Endocr Disord. 2016 Apr 2;16:16. doi: 10.1186/s12902-016-0096-8.
- Derived from this study: PubMed 26437217Shanik MH, Cao PD, Ludlam WH. HISTORICAL RESPONSE RATES OF SOMATOSTATIN ANALOGUES IN THE TREATMENT OF ACROMEGALY: A SYSTEMATIC REVIEW. Endocr Pract. 2016 Mar;22(3):350-6. doi: 10.4158/EP15913.RA. Epub 2015 Oct 5.
- Derived from this study: PubMed 25103549Sheppard M, Bronstein MD, Freda P, Serri O, De Marinis L, Naves L, Rozhinskaya L, Hermosillo Resendiz K, Ruffin M, Chen Y, Colao A. Pasireotide LAR maintains inhibition of GH and IGF-1 in patients with acromegaly for up to 25 months: results from the blinded extension phase of a randomized, double-blind, multicenter, Phase III study. Pituitary. 2015 Jun;18(3):385-94. doi: 10.1007/s11102-014-0585-6.
- Visit NovartisClinicalTrials.com: Pre-qualify for a trial, and view a list of trials and participating study centers.Link provided by the sponsor.
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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
Novartis study chair
Novartis
95 sites in 27 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Pasireotide and Octreotide in people with Acromegaly, run by Novartis Pharmaceuticals at 95 sites in 27 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 3 inclusion and 5 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 2 Jul 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 95 sites in United States, France, Italy, Brazil, Canada and 22 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 30 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 Level to <2.5 μg/L and the Normalization of IGF-1 (time frame: 12 months). 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 NCT00600886, which also lists 3 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 2 Jul 2017.