Clinical Trial Results:
AN INTERNATIONAL, MULTICENTRIC, PROSPECTIVE, OPEN LABEL STUDY TO ASSESS THE EFFICACY AND SAFETY OF LANREOTIDE AUTOGEL® 120 MG ASSOCIATED TO STANDARD OF CARE IN THE TREATMENT OF CLINICAL SYMPTOMS ASSOCIATED WITH INOPERABLE MALIGNANT INTESTINAL OBSTRUCTION
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Summary
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EudraCT number |
2013-002174-43 |
Trial protocol |
BE |
Global end of trial date |
09 Nov 2017
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Results information
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Results version number |
v1(current) |
This version publication date |
20 Jan 2019
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First version publication date |
20 Jan 2019
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Other versions |
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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 |
A-48-52030-269
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT02275338 | ||
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 |
Guldensporenpark 87, Merelbeke, Belgium, B-9820
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Public contact |
Medical Director, Ipsen, clinical.trials@ipsen.com
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Scientific contact |
Medical Director, 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 |
09 Nov 2017
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
09 Nov 2017
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Global end of trial reached? |
Yes
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Global end of trial date |
09 Nov 2017
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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 assess the efficacy of lanreotide Autogel® 120 milligrams (mg) for the relief of vomiting due to inoperable malignant intestinal obstruction in subjects without nasogastric tube (NGT) and to assess the efficacy of lanreotide Autogel® 120 mg to remove a NGT without the recurrence of vomiting in subjects with an inoperable malignant intestinal obstruction with a NGT.
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Protection of trial subjects |
The study was conducted under the provisions of the Declaration of Helsinki, in accordance with the International Conference on Harmonisation Consolidated Guideline on Good Clinical Practice and in compliance with IECs and informed consent regulations.
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Background therapy |
During treatment with lanreotide Autogel®120 mg, all subjects were also required to take intravenous (IV) corticoids and IV H2 antihistamines. If there was insufficient efficacy at Day 7, step-up medication, butylhyoscine bromide (Buscopan) subcutaneous or IV and Haloperidol IV was also to be taken. | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
19 Nov 2014
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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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 |
Belgium: 52
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Worldwide total number of subjects |
52
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EEA total number of subjects |
52
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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) |
21
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From 65 to 84 years |
28
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85 years and over |
3
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Recruitment
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Recruitment details |
Subjects diagnosed with inoperable malignant intestinal obstruction were recruited into this single arm, open label study in 15 study centres in Belgium between November 2014 and November 2017. | ||||||||||||||||||||||||||
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Pre-assignment
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Screening details |
Overall, 52 subjects were enrolled into this 2 phase study. | ||||||||||||||||||||||||||
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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 |
Not applicable
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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 - All Subjects | ||||||||||||||||||||||||||
Arm description |
All subjects were administered an initial injection of lanreotide Autogel® 120 mg via subcutaneous injection at Day 0 (Phase 1). Subjects who completed the 28 days of Phase 1 and who were responders as defined by the protocol, had the opportunity to enter Phase 2 and receive a second subcutaneous injection of lanreotide Autogel® 120 mg. All subjects continued to receive standard of care throughout the study. | ||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||
Investigational medicinal product name |
Lanreotide Autogel®
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Investigational medicinal product code |
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Other name |
Somatuline Autogel
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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 |
120 mg lanreotide Autogel® was administered via subcutaneous injection in the upper outer quadrant of the buttock on Day 0 and on Day 28 if continuing in Phase 2.
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Baseline characteristics reporting groups
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Reporting group title |
Lanreotide Autogel® 120 mg - All Subjects
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Reporting group description |
All subjects were administered an initial injection of lanreotide Autogel® 120 mg via subcutaneous injection at Day 0 (Phase 1). Subjects who completed the 28 days of Phase 1 and who were responders as defined by the protocol, had the opportunity to enter Phase 2 and receive a second subcutaneous injection of lanreotide Autogel® 120 mg. All subjects continued to receive standard of care throughout the study. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Lanreotide Autogel® 120 mg - All Subjects
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Reporting group description |
All subjects were administered an initial injection of lanreotide Autogel® 120 mg via subcutaneous injection at Day 0 (Phase 1). Subjects who completed the 28 days of Phase 1 and who were responders as defined by the protocol, had the opportunity to enter Phase 2 and receive a second subcutaneous injection of lanreotide Autogel® 120 mg. All subjects continued to receive standard of care throughout the study. | ||
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End point title |
Percentage of Responders Before or at Day 7 [1] | ||||||||||||||
End point description |
The primary endpoint assessed the percentage of responding subjects before or at Day 7. A responder was defined as a subject experiencing ≤2 vomiting episodes/day during at least 3 consecutive days at any timepoint between Day 0 and Day 7 (for subjects without NGT at baseline), or as a subject in whom the NGT had been removed during at least 3 consecutive days at any timepoint between Day 0 and Day 7 without vomiting recurrence (for subjects with NGT at baseline), as recorded on diary cards which were completed every day.
A 1 sided binomial test to compare percentage of responding subjects to theoretical proportion of 30% resulted in p value= 0.0055. The expected proportion of responders using Lanreotide was 50%, 1 sided test, 2.5% significance level alpha and power of 80% using Z-test for binomial proportion.
All subjects who received at least 1 dose of study medication (intention-to-treat [ITT] population) are presented.
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End point type |
Primary
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End point timeframe |
From Day 0 to Day 7
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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: As this was a single arm study no comparative analyses were performed. |
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| No statistical analyses for this end point | |||||||||||||||
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End point title |
Percentage of Responders in Phase 1 | ||||||||||||||||||||
End point description |
This endpoint assessed the overall percentage of responding subjects at the Phase 1 timepoints of Days 14 and 28. A responder was defined as a subject experiencing ≤ 2 vomiting episodes/day during at least 3 consecutive days at any timepoint between Day 0 and Days 14 or 28 (for subjects without NGT at baseline) or as a subject in whom the NGT has been removed, during at least 3 consecutive days without vomiting recurrence, at any timepoint between Day 0 and Days 14 and 28 (for subjects with NGT at baseline), as recorded on diary cards which were completed every day.
Results are presented for all subjects who received at least 1 dose of study medication (ITT population).
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End point type |
Secondary
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End point timeframe |
From Day 0 to Day 28
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| No statistical analyses for this end point | |||||||||||||||||||||
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End point title |
Median Time Between First Lanreotide Autogel® Injection and Clinical Response in Phase 1 | ||||||||
End point description |
The time for clinical response in Phase 1 (up to Day 28) was defined as the time from inclusion (Day 0) to the date of clinical response. A response was defined as occurrence of ≤ 2 vomiting episodes/day for at least 3 consecutive days at any timepoint between Day 0 and Day 28 (for patients without NGT use at baseline) or the removal of NGT for at least 3 consecutive days at any timepoint between Day 0 and Day 28 without vomiting recurrence (for patients with NGT use at baseline). The Kaplan-Meier estimate of median time to clinical response are presented for all subjects who received at least 1 dose of study medication (ITT population).
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End point type |
Secondary
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End point timeframe |
From Day 0 to Day 28
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| No statistical analyses for this end point | |||||||||
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End point title |
Median Change From Baseline in Quality of Life as Assessed by Edmonton Symptom Assessment System (ESAS) in Phase 1 | ||||||||||||||||||||
End point description |
Quality of Life was assessed by both subject and investigator based on the ESAS. The ESAS scale evaluates 9 symptoms common in cancer subjects: pain, tiredness, nausea, depression, anxiety, drowsiness, appetite, wellbeing and shortness of breath. The severity at the time of assessment of each symptom is rated from 0 to 10 on a numerical scale; 0 = symptom is absent and 10 = worst possible severity. Each symptom rating was interpreted independently and a total symptom distress score was calculated for both subject and investigator assessed scores as the sum of the 9 items. Median change from baseline (Day 0) in total symptom distress score, at each of the Phase 1 timepoints is presented and a positive change indicates a worsening condition.
All subjects who received at least 1 dose of study medication (ITT population) and with data available for analysis at each timepoint are presented.
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End point type |
Secondary
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End point timeframe |
Days 0, 7, 14 and 28
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| Notes [2] - Subject: Day 7 n=33, Day 14 n=34, Day 28 n=18 Investigator: Day 7 n=28, Day 14 n=28, Day 28 n=20 |
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| No statistical analyses for this end point | |||||||||||||||||||||
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End point title |
Median Change From Baseline in General Activity as Assessed by the Karnofsky Performance Status (KPS) Scale in Phase 1 | ||||||||||||||
End point description |
The KPS scale was used to quantify subject's general well-being and activities of daily life. Subjects were classified based on their functional impairment and KPS scores range from 0 (death) to 100 (no evidence of disease). KPS scores are classified as 0-40 = unable to care for self; requires equivalent of institutional or hospital care; disease may be progressing rapidly; 50-70 = unable to work; able to live at home and care for most personal needs; varying amount of assistance needed; 80-100 = able to carry on normal activity and to work; no special care needed. Median change from baseline (Day 0) at each of the Phase 1 timepoints is presented and a negative change indicates a worsening condition.
All subjects who received at least 1 dose of study medication (ITT population) and with data available for analysis at each timepoint are presented.
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End point type |
Secondary
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End point timeframe |
Days 0, 7, 14 and 28
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| Notes [3] - Day 7, n=41 Day 14, n=36 Day 28, n=25 |
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| No statistical analyses for this end point | |||||||||||||||
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End point title |
Median Change From Baseline in Number of Daily Episodes of Nausea in Phase 1 | ||||||||||||||
End point description |
The mean number of daily episodes of nausea were calculated as the sum of episodes of nausea reported the last 3 days before the corresponding visit, divided by 3.
The median change from baseline (Day 0) at each of the Phase 1 timepoints is presented and a positive change indicates a worsening condition.
All subjects who received at least 1 dose of study medication (ITT population) and with data available for analysis at each timepoint are presented.
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End point type |
Secondary
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End point timeframe |
Days 0, 7, 14 and 28
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| Notes [4] - Day 7, n=16 Day 14, n=14 Day 28, n=12 |
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| No statistical analyses for this end point | |||||||||||||||
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End point title |
Median Change From Baseline in Abdominal Pain Scores Assessed Using Visual Analogue Scale (VAS) in Phase 1 | ||||||||||||||
End point description |
Abdominal pain was assessed using the VAS numeric pain distress scale. The VAS is a 100-millimetre (10-centimetre) scoring scale on which subjects marked on their perceived level of pain. Score range on VAS is from 0 to 100 where 0 = no pain and 100 = unbearable pain. The median change from baseline (Day 0) at each of the Phase 1 timepoints is presented and a positive change indicates a worsening condition.
All subjects who received at least 1 dose of study medication (ITT population) and with data available for analysis at each timepoint are presented.
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End point type |
Secondary
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End point timeframe |
Days 0, 7, 14 and 28
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| Notes [5] - Day 7, n=39 Day 14, n=37 Day 28, n=23 |
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| No statistical analyses for this end point | |||||||||||||||
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End point title |
Percentage of Responders Before or at Phase 2 Timepoints | ||||||||||||||||||||||||||
End point description |
This endpoint assessed the overall percentage of subjects continuing from Phase 1 and confirmed as a responder at the end of Phase 1, showing a continued response at Days 35, 42 and 56. A responder was defined as a subject experiencing ≤2 vomiting episodes/day during at least 3 consecutive days at any timepoint between Day 0 and Days 35, 42, 56 (for subjects without NGT at baseline), or as a subject in whom the NGT had been removed during at least 3 consecutive days at any timepoint between Day 0 and Days 35, 42, 56 without vomiting recurrence (for subjects with NGT at baseline) as recorded on diary cards which were completed every day.
Results are presented for subjects who received at least 1 dose of study medication (ITT population) and were continuing in Phase 2 of the study.
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End point type |
Secondary
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End point timeframe |
From Day 0 to Day 56
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| No statistical analyses for this end point | |||||||||||||||||||||||||||
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End point title |
Median Change From Baseline in Quality of Life as Assessed by ESAS at Phase 2 Timepoints | ||||||||||||||||||||
End point description |
Quality of Life was assessed by both subject and investigator based on the ESAS. The ESAS scale evaluates 9 symptoms common in cancer subjects: pain, tiredness, nausea, depression, anxiety, drowsiness, appetite, wellbeing and shortness of breath. The severity at the time of assessment of each symptom is rated from 0 to 10 on a numerical scale, 0 = symptom is absent and 10 = worst possible severity. Each symptom rating was interpreted independently and a total symptom distress score was calculated for both subject and investigator assessed scores as the sum of the 9 items. Median change from baseline (Day 0) in total symptom distress score, at each of the Phase 2 timepoints is presented for all subjects who received at least 1 dose of study medication (ITT population) and were continuing in Phase 2 of the study. Only subjects with data available for analysis at each timepoint are presented.
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End point type |
Secondary
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End point timeframe |
Days 0, 35, 42 and 56
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| Notes [6] - Subject: Day 35 n=18, Day 42 n=16, Day 56 n=17 Investigator: Day 35 n=18, Day 42 n=14, Day 56 n=17 |
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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 |
Adverse events and deaths due to all causes were recorded from the time the subject gave informed consent (Day 0) and throughout the study up to Day 56.
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Adverse event reporting additional description |
The safety analysis population includes all subjects who received at least 1 dose of study medication.
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
19.0
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Reporting groups
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Reporting group title |
Lanreotide Autogel® 120 mg - All Subjects
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Reporting group description |
All subjects were administered an initial injection of lanreotide Autogel® 120 mg via subcutaneous injection at Day 0 (Phase 1). Subjects who completed the 28 days of the Phase 1 and who were responders as defined by the protocol, had the opportunity to enter Phase 2 and receive a second subcutaneous injection of lanreotide Autogel® 120 mg. All subjects continued to receive standard of care throughout the study. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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? No | |||
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. | |||
| Results from outcome measures regarding change from baseline in quality of life (ESAS scale), general activity (KPS Scale) and daily episodes of nausea should be interpreted with caution due to small sample sizes. | |||
