Clinical Trial Results:
PHASE IIIb, MULTICENTRE, OPEN-LABEL, SINGLE-ARM, STUDY TO ASSESS THE EFFICACY AND SAFETY OF LANREOTIDE AUTOGEL 120 mg ADMINISTERED EVERY 28 DAYS AS PRIMARY MEDICAL TREATMENT IN ACROMEGALIC PATIENTS WITH MACROADENOMA.
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Summary
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EudraCT number |
2007-000155-34 |
Trial protocol |
NL FR ES SE GB BE CZ FI DE IT |
Global end of trial date |
13 Feb 2012
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Results information
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Results version number |
v1(current) |
This version publication date |
16 Mar 2016
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First version publication date |
16 Mar 2016
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Other versions |
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Summary report(s) |
Publication of results in J Clin Endo Metab |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
2 79 52030 207
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT00690898 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Ipsen
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Sponsor organisation address |
65, quai Georges Gorse, Boulogne Billancourt Cedex, France, 92650
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Public contact |
Medical Director, Endocrinology, Medical Director, Endocrinology
Ipsen, clinical.trials@ipsen.com
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Scientific contact |
Medical Director, Endocrinology, Medical Director, Endocrinology
Ipsen, clinical.trials@ipsen.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
23 Jul 2013
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
13 Feb 2012
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Global end of trial reached? |
Yes
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Global end of trial date |
13 Feb 2012
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
To evaluate the efficacy of Lanreotide Autogel 120 mg when used as primary medical treatment in untreated de novo acromegalic patients with macroadenoma, as assessed by evaluating the change in pituitary tumor volume at Week 48 (after 12 injection – V5) compared to baseline volume (V1).
A 20% reduction from baseline (as measured by MRI at V1) will be considered to be clinically significant.
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Protection of trial subjects |
The study was conducted under the provisions of the Declaration of Helsinki, and in accordance with the International Conference of Harmonisation (ICH) Consolidated Guideline on Good Clinical Practice (GCP) and all local regulatory requirements.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
20 May 2008
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
Yes
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Germany: 10
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Country: Number of subjects enrolled |
Belgium: 2
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Country: Number of subjects enrolled |
Finland: 3
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Country: Number of subjects enrolled |
France: 42
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Country: Number of subjects enrolled |
Italy: 7
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Country: Number of subjects enrolled |
Netherlands: 4
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Country: Number of subjects enrolled |
United Kingdom: 17
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Country: Number of subjects enrolled |
Czech Republic: 3
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Country: Number of subjects enrolled |
Turkey: 2
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Worldwide total number of subjects |
90
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EEA total number of subjects |
88
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
80
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From 65 to 84 years |
10
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85 years and over |
0
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Recruitment
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Recruitment details |
108 participants screened. | ||||||||||||||||
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Pre-assignment
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Screening details |
- | ||||||||||||||||
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Pre-assignment period milestones
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Number of subjects started |
108 [1] | ||||||||||||||||
Number of subjects completed |
90 | ||||||||||||||||
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Pre-assignment subject non-completion reasons
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Reason: Number of subjects |
Consent withdrawn by subject: 2 | ||||||||||||||||
Reason: Number of subjects |
Adverse event, non-fatal: 1 | ||||||||||||||||
Reason: Number of subjects |
Entry criteria: 15 | ||||||||||||||||
| Notes [1] - The number of subjects reported to have started the pre-assignment period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same. Justification: Pre-assignment subject number includes screen failure subjects; whereas worldwide subjects number includes only enrolled subjects. |
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Period 1
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Period 1 title |
Overall Study (overall period)
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Is this the baseline period? |
Yes | ||||||||||||||||
Allocation method |
Non-randomised - controlled
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Blinding used |
Not blinded | ||||||||||||||||
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Arms
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Arm title
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Lanreotide Autogel 120 mg | ||||||||||||||||
Arm description |
Lanreotide Autogel 120 mg injection was administered subcutaneously (SC) every 28 days for 12 courses as primary medical treatment in newly diagnosed acromegaly patients with pituitary tumour. | ||||||||||||||||
Arm type |
Experimental | ||||||||||||||||
Investigational medicinal product name |
Lanreotide autogel
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for injection
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
Patients received Lanreotide Autogel 120 mg administered every 28 days (±one day) via deep subcutaneous route in the upper external quadrant of the buttock, alternating the side at each administration. In order to ensure the performance of all protocol assessments, it was recommended to do the administration in the morning, approximately at 9:00 am after all the study assessments. The dose of Lanreotide Autogel was the same throughout the study. A total of 12 injections were administered during the study.
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Baseline characteristics reporting groups
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Reporting group title |
Lanreotide Autogel 120 mg
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Reporting group description |
Lanreotide Autogel 120 mg injection was administered subcutaneously (SC) every 28 days for 12 courses as primary medical treatment in newly diagnosed acromegaly patients with pituitary tumour. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Lanreotide Autogel 120 mg
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Reporting group description |
Lanreotide Autogel 120 mg injection was administered subcutaneously (SC) every 28 days for 12 courses as primary medical treatment in newly diagnosed acromegaly patients with pituitary tumour. | ||
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End point title |
Percentage of patients With Significant Reduction in Pituitary Tumour Volume (as Measured by MRI) From Baseline Volume (Visit 1) to Week 48 (After 12 Injections at Visit 5) [1] | ||||||||||||
End point description |
A blinded, centrally assessed evaluation of all MRIs was performed. A 20% reduction from the volume at Visit 1 was considered to be clinically relevant.
Analysis based on intent-to-treat (ITT) population comprised of 89 patients.
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End point type |
Primary
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End point timeframe |
Week 1 (Baseline) and 48
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical analysis available. |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Number of Patients With at Least a 20% Reduction in Tumour Volume From Baseline Volume (Visit 1) to Week 12 (Visit 3) and Week 24 (Visit 4) | ||||||||||||||
End point description |
Analysis based on number (n) of subjects in the Intent to Treat population (ITT) with a valid value.
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End point type |
Secondary
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End point timeframe |
Week 1 (Baseline), 12 and 24
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| No statistical analyses for this end point | |||||||||||||||
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End point title |
Percent Variation From Baseline to Visit 3, 4 and 5 (Week 12, 24, and 48) of IGF-1 Levels | ||||||||||||||
End point description |
Analysis based on number (n) of patients with a valid value in the intent-to-treat (ITT) population.
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End point type |
Secondary
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End point timeframe |
Week 1 (Baseline), 12, 24 and 48
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| No statistical analyses for this end point | |||||||||||||||
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End point title |
Percent Variation From Baseline to Visit 3, 4 and 5 (Week 12, 24, and 48) of Serum GH Levels. | ||||||||||||||
End point description |
Analysis based on number (n) of subjects in the Intent to Treat population (ITT) with a valid value.
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End point type |
Secondary
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End point timeframe |
Week 1 (Baseline), 12, 24 and 48
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| No statistical analyses for this end point | |||||||||||||||
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End point title |
Change From Baseline to Visit 3, 4 and 5 (Week 12, 24, and 48) of Prolactin Levels | ||||||||||||||
End point description |
Analysis based on the number (n) of subjects with baseline level between 20 ng/ml and 100 ng/ml in the ITT population with a valid value.
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End point type |
Secondary
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End point timeframe |
Weeks 12, 24 and 48
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| No statistical analyses for this end point | |||||||||||||||
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End point title |
Percentage of Patients With Improved, Unchanged or Worsened Clinical Signs of Acromegaly (Arthralgia) From Baseline | ||||||||||||||||||||||||||
End point description |
The status of clinical signs of acromegaly assessed by an acromegaly symptoms questionnaire (paper form) completed by the patient at each study visit. The scoring for each clinical sign of acromegaly on the questionnaire is from 0 (no symptom) to 8 (severe, incapacitating symptom). The variation (or no variation) in scores indicate whether the clinical sign of acromegaly had improved, worsened or was unchanged.
Analysis based on the number (n) of subjects in the ITT population with a valid value.
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End point type |
Secondary
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End point timeframe |
Week 1 (Baseline), 12, 24 and 48
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| No statistical analyses for this end point | |||||||||||||||||||||||||||
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End point title |
Percentage of Patients With Improved, Unchanged or Worsened Clinical Signs of Acromegaly (Excessive Perspiration) From Baseline | ||||||||||||||||||||||||||
End point description |
The status of clinical signs of acromegaly assessed by an acromegaly symptoms questionnaire (paper form) completed by the patient at each study visit. The scoring for each clinical sign of acromegaly on the questionnaire is from 0 (no symptom) to 8 (severe, incapacitating symptom). The variation (or no variation) in scores indicate whether the clinical sign of acromegaly had improved, worsened or was unchanged.
Analysis based on the number (n) of subjects in the ITT population with a valid value.
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End point type |
Secondary
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End point timeframe |
Week 1 (Baseline), 12, 24 and 48
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| No statistical analyses for this end point | |||||||||||||||||||||||||||
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End point title |
Percentage of Patients With Improved, Unchanged or Worsened Clinical Signs of Acromegaly (Fatigue) From Baseline | ||||||||||||||||||||||||||
End point description |
The status of clinical signs of acromegaly assessed by an acromegaly symptoms questionnaire (paper form) completed by the patient at each study visit. The scoring for each clinical sign of acromegaly on the questionnaire is from 0 (no symptom) to 8 (severe, incapacitating symptom). The variation (or no variation) in scores indicate whether the clinical sign of acromegaly had improved, worsened or was unchanged.
Analysis based on the number (n) of subjects in the ITT population with a valid value.
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End point type |
Secondary
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End point timeframe |
Week 1 (Baseline), 12, 24 and 48
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| No statistical analyses for this end point | |||||||||||||||||||||||||||
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End point title |
Percentage of Patients With Improved, Unchanged or Worsened Clinical Signs of Acromegaly (Headache) From Baseline | ||||||||||||||||||||||||||
End point description |
The status of clinical signs of acromegaly assessed by an acromegaly symptoms questionnaire (paper form) completed by the patient at each study visit. The scoring for each clinical sign of acromegaly on the questionnaire is from 0 (no symptom) to 8 (severe, incapacitating symptom). The variation (or no variation) in scores indicate whether the clinical sign of acromegaly had improved, worsened or was unchanged.
Analysis based on the number (n) of subjects in the ITT population with a valid value.
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End point type |
Secondary
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End point timeframe |
Week 1 (Baseline), 12, 24 and 48
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| No statistical analyses for this end point | |||||||||||||||||||||||||||
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End point title |
Percentage of Patients With Improved, Unchanged or Worsened Clinical Signs of Acromegaly (Soft Tissue Swelling) From Baseline | ||||||||||||||||||||||||||
End point description |
The status of clinical signs of acromegaly assessed by an acromegaly symptoms questionnaire (paper form) completed by the patient at each study visit. The scoring for each clinical sign of acromegaly on the questionnaire is from 0 (no symptom) to 8 (severe, incapacitating symptom). The variation (or no variation) in scores indicate whether the clinical sign of acromegaly had improved, worsened or was unchanged.
Analysis based on the number (n) of subjects in the ITT population with a valid value.
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End point type |
Secondary
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End point timeframe |
Week 1 (Baseline), 12, 24 and 48
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| No statistical analyses for this end point | |||||||||||||||||||||||||||
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End point title |
Changes in the Global Acromegaly Quality of Life Assessment (AcroQoL) From Baseline | ||||||||||||||
End point description |
Acromegaly Quality of Life Assessment (AcroQoL) questionnaire response scores range from 0 to 100. Higher scores indicate best possible Quality of Life.
Analysis based on the number (n) of subjects in the ITT population with a valid value.
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End point type |
Secondary
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End point timeframe |
Week 1 (Baseline), 12, 24 and 48
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| No statistical analyses for this end point | |||||||||||||||
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Adverse events information
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Timeframe for reporting adverse events |
Up to 28 days after the last Lanreotide Autogel injection.
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Adverse event reporting additional description |
One Lanreotide Autogel subcutaneous (s.c.) injection administered every 28 days for 12 courses as primary medical treatment in newly diagnosed acromegaly patients with pituitary tumour.
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Assessment type |
Non-systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
13.1
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Reporting groups
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Reporting group title |
Lanreotide Autogel 120 mg
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Reporting group description |
Lanreotide Autogel 120 mg injection was administered subcutaneously (SC) every 28 days for 12 courses as primary medical treatment in newly diagnosed acromegaly patients with pituitary tumour. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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30 Jan 2009 |
Amendment 1:
- Change in the name and address of the sponsor.
- Change of timing of follow-up MRIs central readings |
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25 Sep 2009 |
Amendment 2:
This amendment aimed to improve the scientific quality of the study.
Study procedures did not change.
-Inclusion and exclusion criteria amended related to visual field defect (Changes in inclusion and exclusion criteria do affect judgement of any efficacy endpoints, primary or secondary).
-Extension of the recruitment period up to 33 months
From a safety point of view the critical point of this amendment was to maintain the feasibility of a good visual evaluation capability,
ensuring that visual defect that could result from pituitary adenoma change would be detected. |
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Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
