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Trial · Interventional

CompletedPhase 3Results postedRegistry data

Safety and Efficacy of Pasireotide Long Acting Release (LAR) vs. Octreotide LAR in Patients With Active Acromegaly

NCTNCT00600886 (opens ClinicalTrials.gov in a new tab)Other idCSOM230C2305Other id2007-001972-36
Open at ClinicalTrials.govAsk about this trial

Overview

Status
Completed
Phase
Phase 3
Enrollment
358 participants (actual)
Sponsor
Novartis Pharmaceuticals · Industry
Design
Randomized · Triple masking
Countries
27 countries

United States, Argentina, Belgium, Brazil, Canada, China, Colombia, Czechia, Denmark, France, Germany, Greece, Hungary, Israel, Italy, Mexico, Netherlands, Norway, Poland, Russia, South Korea, Spain, Sweden, Switzerland, Taiwan, Turkey (Türkiye), United Kingdom

Start
11 Feb 2008
Primary completion
11 Mar 2016
Completion
11 Mar 2016
First posted
25 Jan 2008 (estimated)
Last update posted
2 Jul 2017
Conditions
Acromegaly

Timeline

1 trial · 1 completed · 1 with posted results

  • Completed
  • Ongoing
  • Not yet recruiting
  • Stopped
  • Estimated dates (est.)
  • Results posted
20082010201220142016
  1. Ph 3

    Safety and Efficacy of Pasireotide Long Acting Release (LAR) vs. Octreotide LAR in Patients With Active Acromegaly

    NCT00600886

    11 Feb 2008 to 11 Mar 2016

Registry summary

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

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.

Interventions

  • PasireotideDrug
  • OctreotideDrug

Arms2

  • Experimental

    Pasireotide LAR

    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.

  • Active comparator

    Octreotide LAR

    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.

Primary outcomes1

Outcomes the sponsor listed as primary.

  1. 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

    Registry description

    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.

Secondary outcomes(20)

  1. Percentage of Participants With a Reduction of Mean GH Level to < 2.5μg/L

    Time frame · 12 Months

    Registry description

    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.

  2. Change From Baseline in Tumor Volume at 12 Months

    Time frame · Baseline, 12 Months

    Registry description

    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.

  3. Percentage of Participants With Normalization of IGF-1

    Time frame · 12 Months

    Registry description

    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.

  4. 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

    Registry description

    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.)

  5. Summary of Mean GH Values

    Time frame · Baseline, Months 3, 6, 9, 12, 16, 19, 22, 25

    Registry description

    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).

  6. 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

    Registry description

    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).

  7. Severity Scores of Acromegaly Symptoms

    Time frame · Baseline, Months 12, 25

    Registry description

    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).

  8. Ring Size

    Time frame · Baseline, Months 12, 25

    Registry description

    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).

  9. Health-related Quality-of-life as Measured by the AcroQoL Questionnaire

    Time frame · Baseline, Months 12, 25

    Registry description

    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).

  10. Summary of Prolactin Levels

    Time frame · Baseline, Months 12, 25

    Registry description

    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).

  11. 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

    Registry description

    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).

  12. Pasireotide Trough Concentrations by Incident Dose

    Time frame · Months 1 - 12

    Registry description

    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.

  13. Octreotide Trough Concentrations by Incident Dose

    Time frame · Months 1 - 12

    Registry description

    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.

  14. 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

    Registry description

    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).

  15. 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

    Registry description

    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.

  16. Percentage of Participants With Normalization of IGF-1

    Time frame · Months 3, 6, 9, 12, 16, 19, 22, 25

    Registry description

    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.

  17. Change From Baseline in Tumor Volume

    Time frame · Baseline, months 6, 12, 19, 25

    Registry description

    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).

  18. 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

    Registry description

    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).

  19. Percentage of Participants With Normalization of IGF-1 After Crossover

    Time frame · Months 3, 6, 9, 12 after crossover

    Registry description

    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).

  20. Summary of Mean GH Values After Crossover

    Time frame · Extension baseline, months 3, 6, 9, 12 after crossover

    Registry description

    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).

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· 12 months

Percentage of Participants With a Reduction of Mean GH Level to <2.5 μg/L and the Normalization of IGF-1

GroupValue (Percentage of Participants)
Pasireotide LAR (Core)31.3
Octreotide LAR (Core)19.2
Secondary and other outcome results(7)
Secondary outcomeNumber· 12 Months

Percentage of Participants With a Reduction of Mean GH Level to < 2.5μg/L

GroupValue (Percentage of participants)
Pasireotide LAR (Core)48.3
Octreotide LAR (Core)51.6
Secondary outcomeMean· Baseline, 12 Months

Change From Baseline in Tumor Volume at 12 Months

GroupValue (mm^3)Spread
Pasireotide LAR (Core)2420.74159.21
Octreotide LAR (Core)2259.23390.20
Secondary outcomeNumber· 12 Months

Percentage of Participants With Normalization of IGF-1

GroupValue (Percentage of participants)
Pasireotide LAR (Core)38.6
Octreotide LAR (Core)23.6
Secondary outcomeNumber· Months 3, 6, 9, 12, 16, 19, 22, 25

Percentage of Participants With a Reduction of Mean GH Level to < 2.5μg/L and Normalization of IGF-1

GroupValue (Percentage of participants)
Pasireotide LAR (Core & Extension)30.1
Octreotide LAR (Core & Extension)21.4
Secondary outcomeMean· Baseline, Months 3, 6, 9, 12, 16, 19, 22, 25

Summary of Mean GH Values

GroupValue (μg/L)Spread
Pasireotide LAR (Core & Extension)21.932.14
Octreotide LAR (Core & Extension)18.825.95
Secondary outcomeMedian· Up to 26 months

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) )

GroupValue (Weeks)
Pasireotide LAR (Core & Extension)12.6
Octreotide LAR (Core & Extension)12.4
Secondary outcomeMean· Baseline, Months 12, 25

Severity Scores of Acromegaly Symptoms

GroupValue (scores on a scale)Spread
Pasireotide LAR (Core & Extension)0.91.05
Octreotide LAR (Core & Extension)1.01.14

Adverse events, as posted

Adverse events as posted: participants affected out of participants at risk, by group
GroupDeathsSerious eventsOther events
Pasireotide LAR - up to 26 MonthsIncludes data from both blinded core and extension phase (up to Month 26 cutoff date of 29-Dec-2011) for patients who continued the same treatment (Pasireotide LAR) as in the core. For patients who switched from blinded Pasireotide LAR to Octreotide LAR treatment, only data collected before crossover is included.–35 / 178169 / 178
Octreotide LAR - up to 26 MonthsIncludes data from both blinded core and extension phase (up to Month 26 cutoff date of 29-Dec-2011) for patients who continued the same treatment (Octreotide LAR) as in the core. For patients who switched from blinded Octreotide LAR to Pasireotide LAR treatment, only data collected before crossover is included.–28 / 180161 / 180
Crossed Over to Pasireotide LAR - up to 26 MonthsIncludes all data in the extension phase (up to 26-Month cutoff date of 29-Dec-2011) collected after the crossover time point for patients who crossed over from Octreotide LAR in the core to Pasireotide LAR treatment in the extension phase.–8 / 8174 / 81
Crossed Over to Octreotide LAR - up to 26 MonthsIncludes all data in the extension phase (up to 26-Month cutoff date of 29-Dec-2011) collected after the crossover time point for patients who crossed over from Pasireotide LAR in the core to Octreotide LAR treatment in the extension phase.–6 / 3833 / 38
Pasireotide LAR - up to EOSIncludes data from both core and extension phase (up to End-of-study date of 11-Mar-2016) for patients who continued the same treatment (Pasireotide LAR) as in the core. For patients who switched from blinded Pasireotide LAR to Octreotide LAR treatment, only data collected before crossover is included. Per protocol, patients on Pasireotide LAR could continue to receive open-label Pasireotide LAR after treatment unblinding at Month 26, whereas those on Octreotide LAR were not followed after Month 26.–37 / 178170 / 178
Crossed Over to Pasireotide LAR - up to EOSIncludes all data in the extension phase (up to End-of-study date of 11-Mar-2016) collected after the crossover time point for patients who crossed over from Octreotide LAR in the core to Pasireotide LAR treatment in the extension phase. Per protocol, patients on Pasireotide LAR could continue to receive open-label Pasireotide LAR after treatment unblinding at Month 26, whereas those on Octreotide LAR were not followed after Month 26.–12 / 8176 / 81

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

1 study on this page

Indexing hint: Randomized controlled trial · 2016

14 results

Switching patients with acromegaly from octreotide to pasireotide improves biochemical control: crossover extension to a randomized, double-blind, Phase III study.

Bronstein et al. 2016BMC endocrine disorderscited by 62

PMID 27039081PMC4818908DOI 10.1186/s12902-016-0096-8PUB-27039081

CC BY14 results
Download PDFSee results (14)

More studies

1 study on this page

Indexing hint: Randomized controlled trial · 2015

Corrected

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.

Sheppard et al. 2015Pituitarycited by 63

PMID 25103549PMC4424273DOI 10.1007/s11102-014-0585-6PUB-25103549

CC BY
Download PDFRead the notice

Other registry references

References listed at the registry that are not in PepBank. They link to PubMed.

  • DerivedShanik 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. PMID 26437217

Eligibility

Who could join, as posted.

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

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