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Phase 3 N=358 Randomized Triple-blind Treatment

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

Acromegaly

Enrolled (actual)
358
Serious AEs
17.1%
Results posted
Jan 2015
Primary outcome: Primary: Percentage of Participants With a Reduction of Mean GH Level to <2.5 μg/L and the Normalization of IGF-1 — 31.3; 19.2; 39.4; 21.8 Percentage of Participants — p=0.007

Study Design & Population

Study type
Interventional
Phase
Phase 3
Interventions
Pasireotide (Drug); Octreotide (Drug)
Age
Adult, Older Adult · 18+ yrs
Sex
All
Sponsor
Novartis Pharmaceuticals
Primary completion
Mar 2016

Outcome Measures

OutcomeResultp-value
PRIMARY
Percentage of Participants With a Reduction of Mean GH Level to <2.5 μg/L and the Normalization of IGF-1
31.3; 19.2; 39.4; 21.8; 25.7; 17.3 0.007 sig
SECONDARY
Percentage of Participants With a Reduction of Mean GH Level to < 2.5μg/L
49.4; 43.4; 45.5; 47.8; 42.6; 46.2
SECONDARY
Change From Baseline in Tumor Volume at 12 Months
2420.7; 2259.2; -39.7; -38.0; 2185.2; 2196.5
SECONDARY
Percentage of Participants With Normalization of IGF-1
35.2; 25.3; 35.8; 24.2; 34.1; 28.0
SECONDARY
Percentage of Participants With a Reduction of Mean GH Level to < 2.5μg/L and Normalization of IGF-1
30.1; 21.4; 30.1; 19.8; 27.8; 23.1
SECONDARY
Summary of Mean GH Values
21.9; 18.8; 6.3; 5.8; 5.6; 5.2
SECONDARY
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) )
12.6; 12.4
SECONDARY
Severity Scores of Acromegaly Symptoms
0.9; 1.0; 1.2; 1.4; 1.1; 1.3
SECONDARY
Ring Size
11.6; 11.8; 11.7; 12.4; 12.5; 11.4
SECONDARY
Health-related Quality-of-life as Measured by the AcroQoL Questionnaire
58.4; 55.6; 65.7; 61.6; 69.3; 62.9
SECONDARY
Summary of Prolactin Levels
20.6; 15.8; 8.9; 11.7; 5.4; 6.7
SECONDARY
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)
64.4; 64.6
SECONDARY
Pasireotide Trough Concentrations by Incident Dose
4.65; 6.65; 2.88; 7.81; 3.39; 8.70
SECONDARY
Octreotide Trough Concentrations by Incident Dose
0.86; 0.61; 1.21; 0.62; 1.29; 0.19
SECONDARY
Percentage of Participants With a Reduction of Mean GH Level to < 2.5μg/L and Normalization of IGF-1 After Crossover
17.3; 2.6; 21.0; 2.6; 22.2; 5.3
SECONDARY
Percentage of Participants With a Reduction of Mean GH Level to < 2.5μg/L
49.4; 43.4; 45.5; 47.8; 42.6; 46.2
SECONDARY
Percentage of Participants With Normalization of IGF-1
35.2; 25.3; 35.8; 24.2; 34.1; 28.0
SECONDARY
Change From Baseline in Tumor Volume
2420.7; 2259.2; 1614.1; 1565.4; 1482.4; 1390.4
SECONDARY
Percentage of Participants With a Reduction of Mean GH Level to < 2.5μg/L After Crossover
49.4; 28.9; 43.2; 31.6; 54.3; 31.6
SECONDARY
Percentage of Participants With Normalization of IGF-1 After Crossover
19.8; 7.9; 30.9; 7.9; 29.6; 10.5
SECONDARY
Summary of Mean GH Values After Crossover
5.9; 7.1; 5.9; 9.8; 4.8; 9.8
SECONDARY
Change From Extension Baseline in Tumor Volume After Crossover
1420.9; 1809.6; 1027.5; 1794.9; -18.1; -12.3
SECONDARY
Severity Scores of Acromegaly Symptoms After Crossover
0.6; 0.4; 0.5; 0.7; 0.8; 0.7
SECONDARY
Ring Size After Crossover
11.2; 11.0; 11.6; 12.3; 11.4; 12.4
SECONDARY
Health-related Quality-of-life as Measured by the AcroQoL Questionnaire After Crossover
58.9; 59.8; 60.3; 61.2
SECONDARY
Summary of Prolactin Levels After Crossover
11.9; 15.7; 7.5; 16.1

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 (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.

Eligibility Criteria

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

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT00600886). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.

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