CLARINET FORTE: Efficacy and Safety Study in Pancreatic or Midgut Neuroendocrine Tumours Having Progressed Radiologically While Previously Treated With Lanreotide Autogel® 120 mg
Sponsor
Ipsen (Industry)
Overall Status
Completed
CT.gov ID
NCT02651987
Collaborator
(none)
99
32
1
47.1
3.1
0.1
Study Details
Study Description
Brief Summary
This study aims to explore the efficacy and safety of lanreotide Autogel® 120 mg administered every 14 days in subjects with grade 1 or 2, metastatic or locally advanced, unresectable pancreatic or intestinal neuroendocrine tumours (NETs) once they have progressed on the standard dose of lanreotide Autogel® 120 mg every 28 days.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
99 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Efficacy and Safety of Lanreotide Autogel® 120 mg Administered Every 14 Days in Well Differentiated, Metastatic or Locally Advanced, Unresectable Pancreatic or Midgut Neuroendocrine Tumours Having Progressed Radiologically While Previously Treated With Lanreotide Autogel® 120 mg Administered Every 28 Days
Actual Study Start Date
:
Nov 19, 2015
Actual Primary Completion Date
:
Oct 16, 2019
Actual Study Completion Date
:
Oct 24, 2019
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Lanreotide Autogel® One subcutaneous (SC) injection of lanreotide Autogel® 120mg every 14 days until disease progression or death or unacceptable toxicity or tolerability. |
Drug: Lanreotide autogel 120 mg
|
Outcome Measures
Primary Outcome Measures
- Median Progression Free Survival (PFS) [From Day 1 up to Week 60 for the panNET cohort and Week 103 for the midgut NET cohort]
PFS was defined as the time from first injection of lanreotide Autogel® 120 mg every 14 days to progression or death. Disease progression was assessed by tumour response evaluation according to RECIST v1.0, every 12 weeks, measured by independent central review using the same imaging technique (computed tomography [CT] scan or magnetic resonance imaging [MRI]) for each subject throughout the study. The median PFS time was estimated using the Kaplan Meier method for each cohort.
Secondary Outcome Measures
- Median Time to Progression [From Day 1 up to Week 60 for the panNET cohort and Week 103 for the midgut NET cohort]
Time to Progression was defined as time from first injection of lanreotide Autogel® 120 mg every 14 days to progression. Disease progression was assessed by tumour response evaluation according to RECIST v1.0, every 12 weeks, measured by independent central review using the same imaging technique (CT scan or MRI) for each subject throughout the study. Median time to progression was estimated using the Kaplan Meier method for each cohort.
- Percentage of Subjects Alive and Progression Free [Weeks 12, 24, 36, 48, 60 (for both cohorts) and Weeks 72, 84 and 96 (for midgut NET cohort)]
The percentage of subjects alive and progression-free was assessed throughout the study up to Week 60 for the panNET cohort and Week 96 for the midgut cohort. Disease progression was assessed by tumour response evaluation according to RECIST v1.0, every 12 weeks measured by independent central review using the same imaging technique (CT scan or MRI) for each subject throughout the study. The percentage of subjects alive and progression free was estimated using the Kaplan Meier method for each cohort.
- Overall Survival [From Day 1 up to Week 60 for the panNET cohort and Week 103 for the midgut NET cohort]
Overall survival was defined as the time in months from the first injection of lanreotide Autogel® 120 mg every 14 days to death due to any cause. Median overall survival was estimated using the Kaplan Meier method for each cohort.
- Objective Response Rate (ORR) [Weeks 12, 24, 36, 48, 60 (for both cohorts) and Weeks 72, 84, and 96 (for midgut cohort)]
The ORR was defined as the percentage of subjects who achieve either complete response (CR) or partial response (PR) according to RECIST v1.0 criteria. ORR was evaluated every 12 weeks and results are presented for each cohort.
- Disease Control Rate (DCR) [Weeks 24 and 48]
The DCR was defined as the percentage of subjects who achieved CR plus PR plus Stable Disease (SD), evaluated according to RECIST v1.0 criteria. The DCR at Weeks 24 and 48 is presented for each cohort.
- Best Overall Response Rate [From Day 1 up to Week 60 for the panNET cohort and Week 103 for the midgut NET cohort]
Best overall response was defined as the best response recorded from the initiation of treatment until disease progression, according to RECIST v1.0 evaluation. The percentage of subjects in each response category and those who were non-evaluable (i.e. with no tumour assessment after the start of study treatment) throughout the study are presented for each cohort.
- Median Duration of Stable Disease [From Day 1 up to Week 60 for the panNET cohort and Week 103 for the midgut NET cohort]
Median duration of SD was the time from first injection of lanreotide Autogel® 120 mg every 14 days until the first occurrence of PD by central assessment. Disease progression was assessed by tumour response evaluation according to RECIST v1.0, every 12 weeks, measured using the same imaging technique (CT scan or MRI) for each subject throughout the study. Median duration of stable disease was estimated using the Kaplan Meier method for each cohort.
- Factors Associated With PFS [Screening/Baseline (Day 1)]
A univariate cox proportional hazards model was used to assess whether the following factors were associated with PFS: Hepatic tumour load: >25% versus reference ≤25% Tumour Grade: Grade 2 versus reference Grade 1, Previous surgery of the primary tumour: No versus reference Yes, Proliferation index Ki67: ≥10% versus reference <10% Duration of treatment with lanreotide Autogel® 120 mg every 28 days by category: ≥median value versus reference <median value, Age by category: ≥65 years versus reference <65 years, Time from diagnosis to study entry by category: ≥3 years versus reference <3 years, Time interval between the two CT scans (pre-screening/screening): ≥12 months versus reference <12 months and Symptoms (diarrhoea or flushing at baseline): No versus reference Yes. Each factor was assessed for its importance in the Cox model for PFS in a univariate fashion.
- Mean Change From Baseline in Number of Stools and Flushing Episodes [Baseline (Day 1), Weeks 8,12, 48 and end of study (approximately 64 weeks for panNET cohort and 108 weeks for midgut NET cohort)]
Symptom control was measured by the total number of stools (diarrhoea) and flushing episodes during the 7 days prior to the visit, reported orally by the subject to the investigator. The mean change from baseline in number of stools and flushing episodes reported at each visit is presented for each cohort.
- Mean Change From Baseline in QoL Measured Using EORTC, QLQ-C30 v3.0 (Global Health Status Sub-score) [Baseline (Day 1) and end of study (approximately 64 weeks for panNET cohort and 108 weeks for midgut NET (and overall) cohort)]
Subjects were instructed to complete the 30 questions in the EORTC-QLQ-C30 v3.0 questionnaire at baseline and every 12 weeks throughout the study. The global health status sub-score was assessed using the last 2 questions which represented subject's assessment of overall health & QoL. Each question was coded on a 7-point scale (1=very poor to 7=excellent). The sub-score was transformed to range from 0-100, with a high score for global health status representing a high QoL. The mean change from baseline in the transformed global health status are presented for the end of study/early withdrawal visit, with a positive change indicating an improvement in QoL.
- Mean Change From Baseline in EQ-5D-5L v1.0 Questionnaire (Descriptive System) [Baseline (Day 1) and end of study (approximately 64 weeks for panNET cohort and 108 weeks for midgut NET (and overall) cohort)]
Subjects were instructed to complete the EQ-5D-5L descriptive system at baseline and every 12 weeks throughout the study. The EQ-5D-5L descriptive system comprised the following 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension had 5 levels: no problems, slight problems, moderate problems, severe problems, extreme problems. The EQ-5D-5L health states, defined by the EQ-5D-5L descriptive system, was converted into a single index value with scores ranging from 0 (no problems) to 1 (extreme problems). The mean change from baseline at the end of study/early withdrawal visit is presented with a positive change from baseline in the index values indicating a worsening of symptoms.
- Mean Change From Baseline in EQ-5D-5L v1.0 Questionnaire (VAS) [Baseline (Day 1) and end of study (approximately 64 weeks for panNET cohort and 108 weeks for midgut NET (and overall) cohort)]
Subjects were instructed to complete the EQ-5D-5L VAS at baseline and every 12 weeks throughout the study. The EQ-5D-5L VAS recorded the subject's self-rated health on a vertical VAS which is numbered from 0 (worst health state) to 100 (best health state). The mean change from baseline at the end of study/early withdrawal visit is presented with a positive change in the VAS indicating an improvement in symptoms.
- Mean Change From Baseline in QoL Questionnaire Gastrointestinal Neuroendocrine Tumour 21 (QLQ-GI.NET21; 2006) [Baseline (Day 1) and end of study (approximately 64 weeks for panNET cohort and 108 weeks for midgut NET (and overall) cohort)]
Subjects were asked to complete the EORTC QLQ-GI.NET21 module which comprised 21 questions that used a 4-point scale (1 = Not at all, 2 = A little, 3 = Quite a bit, 4 = Very much) to evaluate 3 defined multi-item symptom scales (endocrine, gastrointestinal and treatment related side effects), 2 single item symptoms (bone/muscle pain and concern about weight loss), 2 psychosocial scales (social function and disease-related worries) and 2 other single items (sexuality and communication). Answers were converted into grading scale, with values between 0 and 100. Each individual sub-score was transformed to range from 0 to 100. The mean change from baseline at the end of study/early withdrawal visit is presented with a higher score representing more or worse problems.
- Mean Change From Baseline in Nonspecific Tumour Biomarkers [Baseline (Day 1) and end of study (approximately 64 weeks for panNET cohort and 108 weeks for midgut NET cohort)]
Nonspecific tumour peptide biomarkers (chromogranin A [CgA], neuron specific enolase [NSE] and plasma/urinary 5-hydroxyindoleacetic acid [5-HIAA]) were evaluated in both pancreas and midgut subjects at baseline and Week 12 and every 12 weeks thereafter. At all scheduled visits, except baseline, plasma/urinary 5-HIAA was only performed in subjects with symptoms of carcinoid syndrome (diarrhoea and/or flushing) or if urinary 5-HIAA was elevated (above upper limit of normal [ULN]) at baseline. Mean change from baseline values were normalised by the ULN (xULN) and are presented for each cohort.
- Mean Change From Baseline in PanNet Specific Tumour Biomarkers: Pancreatic Polypeptide, Gastrin [Baseline (Day 1) and end of study (approximately 64 weeks)]
PanNET specific tumour peptide biomarkers were evaluated in pancreas subjects at baseline. Only the tumour biomarkers that were above normal range at baseline were evaluated every 12 weeks thereafter and at the end of study visit. The mean change from baseline values in picomole/liter (pmol/L) are presented for the end of study visit.
- Mean Change From Baseline in PanNet Specific Tumour Biomarkers: Glucagon [Baseline (Day 1) and end of study (approximately 64 weeks)]
PanNET specific tumour peptide biomarkers were evaluated in pancreas subjects at baseline. Only the tumour biomarkers that were above normal range at baseline were evaluated every 12 weeks thereafter and at the end of study visit. The mean change from baseline values in nanograms (ng)/L are presented for the end of study visit.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Histopathologically confirmed, grade 1 or 2, metastatic or locally advanced, unresectable pNET (pNET cohort) or midgut NET (midgut cohort) with or without hormone related syndromes, with a proliferation index (Ki67) ≤20%.
-
Positive somatostatin receptors type 2
-
Progression as assessed by an independent central reviewer according to RECIST v1.0 while receiving first line treatment with lanreotide Autogel® at a standard dose of 120 mg every 28 days for at least 24 weeks
Exclusion Criteria:
-
Grade 3 or rapidly progressive (within 12 weeks) NET
-
Any NET other than pancreatic and midgut
-
Previous treatment with any antitumour agent for NET other than lanreotide Autogel® 120 mg every 28 days. Exception made of prior treatment with Octreotide at standard dose stopped for other reason than disease progression.
-
Symptomatic gallbladder lithiasis at screening echography or history of cholelithiasis with no cholecystectomy since then.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Erasme Hospital | Bruxelles | Belgium | 1070 | |
| 2 | Cliniques Unversitaires Saint Luc | Bruxelles | Belgium | 1200 | |
| 3 | Antwerp University Hospital | Edegem | Belgium | 2650 | |
| 4 | UZ Leuven | Leuven | Belgium | B-3000 | |
| 5 | Aarhus University Hospital | Aarhus | Denmark | ||
| 6 | Rigshospitalet | København | Denmark | 2100 | |
| 7 | Hôpital Beaujon | Clichy | France | 92118 | |
| 8 | Hôpital Edouard Herriot | Lyon | France | 69437 | |
| 9 | Institut Paoli Calmette | Marseille | France | 13273 | |
| 10 | Institut Gustave Roussy | Villejuif | France | 94805 | |
| 11 | Charité - CVK | Berlin | Germany | 13353 | |
| 12 | Universitätsklinikum Erlangen | Erlangen | Germany | 91054 | |
| 13 | Nationales Centrum für Tumorerkrankungen (NCT) | Heidelberg | Germany | 69120 | |
| 14 | St Vincent's University Hospital | Dublin | Ireland | D4 | |
| 15 | IRCCS Azienda Ospedaliera Universitaria | San Martino | Genova | Italy | 16132 |
| 16 | Azienda Ospedaliera - Universitaria Careggi | Firenze | Italy | 50134 | |
| 17 | Fondacione IRCCS Istituto Nazionale Dei Tumori | Milano | Italy | 20133 | |
| 18 | Università degli Studi "Federico II" di Napoli | Napoli | Italy | 80131 | |
| 19 | Azienda Ospedaliera sant'Andrea | Roma | Italy | 00189 | |
| 20 | AVL/NKI Medisch Oncologie | Amsterdam | Netherlands | 1066 | |
| 21 | Academic Medical Center | Amsterdam | Netherlands | 1105 | |
| 22 | Erasmus MC | Rotterdam | Netherlands | 3015 | |
| 23 | Samodzielny Publiczny Szpital Kliniczny nr 5 | Katowice | Poland | 40-952 | |
| 24 | Katedra i Klinika Endokrynologii | Poznan | Poland | 60-355 | |
| 25 | Centrum Diagnostyczno-Lecznicze "GAMMED" | Warsaw | Poland | 02-348 | |
| 26 | Hospital Universitario Vall D'hebron | Barcelona | Spain | 08034 | |
| 27 | Hospital Universitario Ramón Y Cajal | Madrid | Spain | 28034 | |
| 28 | Hospital Universitario 12 De Octubre | Madrid | Spain | 28041 | |
| 29 | Hospital Universitario Central de Asturias | Oviedo | Spain | 33011 | |
| 30 | Queen Elizabeth Medical Center | Birmingham | United Kingdom | B15 2TH | |
| 31 | Royal Free Hospital | London | United Kingdom | NW3 2QG | |
| 32 | The Christie Hospital NHS Foundation Trust | Manchester | United Kingdom | M20 4BX |
Sponsors and Collaborators
- Ipsen
Investigators
- Study Director: Ipsen Medical Director, Ipsen
Study Documents (Full-Text)
More Information
Publications
None provided.Responsible Party:
Ipsen
ClinicalTrials.gov Identifier:
NCT02651987
Other Study ID Numbers:
- 8-79-52030-326
- 2014-005607-24
First Posted:
Jan 11, 2016
Last Update Posted:
Dec 30, 2020
Last Verified:
Dec 1, 2020
Study Results
Participant Flow
| Recruitment Details | Subjects with well differentiated, metastatic or locally advanced, unresectable, pancreatic or midgut neuroendocrine tumours (NETs) and who had radiologically documented disease progression as per Response Evaluation Criteria in Solid Tumours (RECIST) v1.0 whilst receiving treatment with lanreotide Autogel® 120mg, every 28 days for at least 24 weeks were enrolled into this study in 25 centres across 10 countries. |
|---|---|
| Pre-assignment Detail | Subjects who had centrally reviewed, radiologically documented disease progression within 24 months prior to enrolment and whilst receiving treatment with lanreotide Autogel® 120 mg, administered every 28 days for at least 24 weeks, were recruited into one of two cohorts based on the primary location of NET (i.e. pancreatic NET [panNET] or midgut NET cohort). |
| Arm/Group Title | Pancreatic NET (panNET) Cohort | Midgut NET Cohort |
|---|---|---|
| Arm/Group Description | Subjects were treated with lanreotide Autogel® 120 mg, administered as deep subcutaneous (SC) injections, every 14 days starting from Day 1 (at a reduced dosing interval) for up to 48 weeks or until disease progression, death or unacceptable toxicity or tolerability. Subjects who had not progressed at Week 48 could continue study treatment with lanreotide Autogel® 120 mg every 14 days until 25 events (progressive disease [PD] or death) in the panNET cohort had been observed. Additional visits were performed every 12 weeks until disease progression or death, or unacceptable toxicity or tolerability. | Subjects were treated with lanreotide Autogel® 120 mg, administered as deep SC injections, every 14 days starting from Day 1 (at a reduced dosing interval) for up to 96 weeks or until disease progression, death or unacceptable toxicity or tolerability. Subjects who had not progressed at Week 96 could continue study treatment with lanreotide Autogel® 120 mg every 14 days until 25 events (PD or death) in the midgut NET cohort had been observed. Additional visits were performed every 12 weeks until disease progression or death, or unacceptable toxicity or tolerability. |
| Period Title: Overall Study | ||
| STARTED | 48 | 51 |
| COMPLETED | 43 | 46 |
| NOT COMPLETED | 5 | 5 |
Baseline Characteristics
| Arm/Group Title | PanNET Cohort | Midgut NET Cohort | Total |
|---|---|---|---|
| Arm/Group Description | Subjects were treated with lanreotide Autogel® 120 mg, administered as deep SC injections, every 14 days starting from Day 1 (at a reduced dosing interval) for up to 48 weeks or until disease progression, death or unacceptable toxicity or tolerability. Subjects who had not progressed at Week 48 could continue study treatment with lanreotide Autogel® 120 mg every 14 days until 25 events (PD or death) in the panNET cohort had been observed. Additional visits were performed every 12 weeks until disease progression or death, or unacceptable toxicity or tolerability. | Subjects were treated with lanreotide Autogel® 120 mg, administered as deep SC injections, every 14 days starting from Day 1 (at a reduced dosing interval) for up to 96 weeks or until disease progression, death or unacceptable toxicity or tolerability. Subjects who had not progressed at Week 96 could continue study treatment with lanreotide Autogel® 120 mg every 14 days until 25 events (PD or death) in the midgut NET cohort had been observed. Additional visits were performed every 12 weeks until disease progression or death, or unacceptable toxicity or tolerability. | Total of all reporting groups |
| Overall Participants | 48 | 51 | 99 |
| Age (years) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [years] |
63.3
(10.6)
|
67.1
(8.2)
|
65.2
(9.6)
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
28
58.3%
|
22
43.1%
|
50
50.5%
|
| Male |
20
41.7%
|
29
56.9%
|
49
49.5%
|
| Race/Ethnicity, Customized (Count of Participants) | |||
| Asian |
0
0%
|
1
2%
|
1
1%
|
| White |
35
72.9%
|
37
72.5%
|
72
72.7%
|
| Other |
1
2.1%
|
0
0%
|
1
1%
|
| Region of Enrollment (participants) [Number] | |||
| Netherlands |
1
2.1%
|
3
5.9%
|
4
4%
|
| Belgium |
3
6.3%
|
2
3.9%
|
5
5.1%
|
| Ireland |
2
4.2%
|
0
0%
|
2
2%
|
| Denmark |
1
2.1%
|
2
3.9%
|
3
3%
|
| Poland |
12
25%
|
10
19.6%
|
22
22.2%
|
| Italy |
2
4.2%
|
6
11.8%
|
8
8.1%
|
| United Kingdom |
6
12.5%
|
9
17.6%
|
15
15.2%
|
| France |
12
25%
|
13
25.5%
|
25
25.3%
|
| Germany |
8
16.7%
|
3
5.9%
|
11
11.1%
|
| Spain |
1
2.1%
|
3
5.9%
|
4
4%
|
| Quality of Life (QoL) Questionnaire Core 30 (QLQ-C30) Score (score on a scale) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [score on a scale] |
68.12
(19.74)
|
67.83
(20.76)
|
67.97
(20.17)
|
| EuroQoL 5 Dimensions, 5 Levels (EQ-5D-5L) v1.0 Questionnaire Descriptive System Score (score on a scale) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [score on a scale] |
0.82
(0.17)
|
0.83
(0.14)
|
0.83
(0.15)
|
| EQ-5D-5L Visual Analogue Scale (VAS) Score (score on a scale) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [score on a scale] |
75.02
(17.93)
|
70.45
(14.93)
|
72.81
(16.62)
|
| QoL Questionnaire Gastrointestinal Neuroendocrine Tumour 21 (QLQ-GI.NET21) Score (score on a scale) [Mean (Standard Deviation) ] | |||
| Endocrine Symptoms |
16.54
(22.30)
|
19.73
(22.82)
|
18.20
(22.51)
|
| Gastrointestinal Symptoms |
21.70
(20.01)
|
22.04
(17.17)
|
21.88
(18.48)
|
| Treatment Related Symptoms |
11.63
(13.11)
|
11.46
(13.75)
|
11.55
(13.33)
|
| Social Function |
32.84
(24.18)
|
35.03
(24.33)
|
33.98
(24.15)
|
| Disease Related Worries |
44.44
(29.96)
|
44.22
(25.83)
|
44.33
(27.74)
|
| Muscle/Bone Pain |
26.52
(30.99)
|
25.69
(30.16)
|
26.09
(30.39)
|
| Sexual Function |
22.58
(30.29)
|
17.86
(27.94)
|
20.34
(29.04)
|
| Information/Communication Function |
3.70
(12.76)
|
4.17
(11.14)
|
3.94
(11.89)
|
| Body Image |
10.61
(23.60)
|
15.56
(28.95)
|
13.11
(26.41)
|
| Categories of Proliferation index Ki67 (participants) [Number] | |||
| ≥10% |
7
14.6%
|
4
7.8%
|
11
11.1%
|
| <10% |
41
85.4%
|
46
90.2%
|
87
87.9%
|
| Missing |
0
0%
|
1
2%
|
1
1%
|
| Tumour grading (according to WHO 2010 classification) (participants) [Number] | |||
| Grade 1 |
12
25%
|
29
56.9%
|
41
41.4%
|
| Grade 2 |
36
75%
|
22
43.1%
|
58
58.6%
|
| Hepatic tumour load (participants) [Number] | |||
| >25% |
7
14.6%
|
9
17.6%
|
16
16.2%
|
| ≤25% |
41
85.4%
|
42
82.4%
|
83
83.8%
|
Outcome Measures
| Title | Median Progression Free Survival (PFS) |
|---|---|
| Description | PFS was defined as the time from first injection of lanreotide Autogel® 120 mg every 14 days to progression or death. Disease progression was assessed by tumour response evaluation according to RECIST v1.0, every 12 weeks, measured by independent central review using the same imaging technique (computed tomography [CT] scan or magnetic resonance imaging [MRI]) for each subject throughout the study. The median PFS time was estimated using the Kaplan Meier method for each cohort. |
| Time Frame | From Day 1 up to Week 60 for the panNET cohort and Week 103 for the midgut NET cohort |
Outcome Measure Data
| Analysis Population Description |
|---|
| The FAS included all subjects who received at least one dose of lanreotide Autogel® 120 mg every 14 days during the study. |
| Arm/Group Title | PanNET Cohort | Midgut NET Cohort |
|---|---|---|
| Arm/Group Description | Subjects were treated with lanreotide Autogel® 120 mg, administered as SC injections, every 14 days starting from Day 1 (at a reduced dosing interval) for up to 48 weeks or until disease progression, death or unacceptable toxicity or tolerability. Subjects who had not progressed at Week 48 could continue study treatment with lanreotide Autogel® 120 mg every 14 days until 25 events (PD or death) in the panNET cohort had been observed. Additional visits were performed every 12 weeks until disease progression or death, or unacceptable toxicity or tolerability. | Subjects were treated with lanreotide Autogel® 120 mg, administered as deep SC injections, every 14 days starting from Day 1 (at a reduced dosing interval) for up to 96 weeks or until disease progression, death or unacceptable toxicity or tolerability. Subjects who had not progressed at Week 96 could continue study treatment with lanreotide Autogel® 120 mg every 14 days until 25 events (PD or death) in the midgut NET cohort had been observed. Additional visits were performed every 12 weeks until disease progression or death, or unacceptable toxicity or tolerability. |
| Measure Participants | 48 | 51 |
| Median (95% Confidence Interval) [months] |
5.6
|
8.3
|
| Title | Median Time to Progression |
|---|---|
| Description | Time to Progression was defined as time from first injection of lanreotide Autogel® 120 mg every 14 days to progression. Disease progression was assessed by tumour response evaluation according to RECIST v1.0, every 12 weeks, measured by independent central review using the same imaging technique (CT scan or MRI) for each subject throughout the study. Median time to progression was estimated using the Kaplan Meier method for each cohort. |
| Time Frame | From Day 1 up to Week 60 for the panNET cohort and Week 103 for the midgut NET cohort |
Outcome Measure Data
| Analysis Population Description |
|---|
| The FAS included all subjects who received at least one dose of lanreotide Autogel® 120 mg every 14 days during the study. |
| Arm/Group Title | PanNET Cohort | Midgut NET Cohort |
|---|---|---|
| Arm/Group Description | Subjects were treated with lanreotide Autogel® 120 mg, administered as SC injections, every 14 days starting from Day 1 (at a reduced dosing interval) for up to 48 weeks or until disease progression, death or unacceptable toxicity or tolerability. Subjects who had not progressed at Week 48 could continue study treatment with lanreotide Autogel® 120 mg every 14 days until 25 events (PD or death) in the panNET cohort had been observed. Additional visits were performed every 12 weeks until disease progression or death, or unacceptable toxicity or tolerability. | Subjects were treated with lanreotide Autogel® 120 mg, administered as deep SC injections, every 14 days starting from Day 1 (at a reduced dosing interval) for up to 96 weeks or until disease progression, death or unacceptable toxicity or tolerability. Subjects who had not progressed at Week 96 could continue study treatment with lanreotide Autogel® 120 mg every 14 days until 25 events (PD or death) in the midgut NET cohort had been observed. Additional visits were performed every 12 weeks until disease progression or death, or unacceptable toxicity or tolerability. |
| Measure Participants | 48 | 51 |
| Median (95% Confidence Interval) [months] |
5.6
|
8.7
|
| Title | Percentage of Subjects Alive and Progression Free |
|---|---|
| Description | The percentage of subjects alive and progression-free was assessed throughout the study up to Week 60 for the panNET cohort and Week 96 for the midgut cohort. Disease progression was assessed by tumour response evaluation according to RECIST v1.0, every 12 weeks measured by independent central review using the same imaging technique (CT scan or MRI) for each subject throughout the study. The percentage of subjects alive and progression free was estimated using the Kaplan Meier method for each cohort. |
| Time Frame | Weeks 12, 24, 36, 48, 60 (for both cohorts) and Weeks 72, 84 and 96 (for midgut NET cohort) |
Outcome Measure Data
| Analysis Population Description |
|---|
| The FAS included all subjects who received at least one dose of lanreotide Autogel® 120 mg every 14 days during the study. |
| Arm/Group Title | PanNET Cohort | Midgut NET Cohort |
|---|---|---|
| Arm/Group Description | Subjects were treated with lanreotide Autogel® 120 mg, administered as SC injections, every 14 days starting from Day 1 (at a reduced dosing interval) for up to 48 weeks or until disease progression, death or unacceptable toxicity or tolerability. Subjects who had not progressed at Week 48 could continue study treatment with lanreotide Autogel® 120 mg every 14 days until 25 events (PD or death) in the panNET cohort had been observed. Additional visits were performed every 12 weeks until disease progression or death, or unacceptable toxicity or tolerability. | Subjects were treated with lanreotide Autogel® 120 mg, administered as deep SC injections, every 14 days starting from Day 1 (at a reduced dosing interval) for up to 96 weeks or until disease progression, death or unacceptable toxicity or tolerability. Subjects who had not progressed at Week 96 could continue study treatment with lanreotide Autogel® 120 mg every 14 days until 25 events (PD or death) in the midgut NET cohort had been observed. Additional visits were performed every 12 weeks until disease progression or death, or unacceptable toxicity or tolerability. |
| Measure Participants | 48 | 51 |
| Week 12 |
93.3
|
91.8
|
| Week 24 |
64.4
|
65.3
|
| Week 36 |
37.8
|
59.2
|
| Week 48 |
28.5
|
38.3
|
| Week 60 |
20.7
|
36.1
|
| Week 72 |
29.8
|
|
| Week 84 |
27.5
|
|
| Week 96 |
25.2
|
| Title | Overall Survival |
|---|---|
| Description | Overall survival was defined as the time in months from the first injection of lanreotide Autogel® 120 mg every 14 days to death due to any cause. Median overall survival was estimated using the Kaplan Meier method for each cohort. |
| Time Frame | From Day 1 up to Week 60 for the panNET cohort and Week 103 for the midgut NET cohort |
Outcome Measure Data
| Analysis Population Description |
|---|
| The FAS included all subjects who received at least one dose of lanreotide Autogel® 120 mg every 14 days during the study. |
| Arm/Group Title | PanNET Cohort | Midgut NET Cohort |
|---|---|---|
| Arm/Group Description | Subjects were treated with lanreotide Autogel® 120 mg, administered as SC injections, every 14 days starting from Day 1 (at a reduced dosing interval) for up to 48 weeks or until disease progression, death or unacceptable toxicity or tolerability. Subjects who had not progressed at Week 48 could continue study treatment with lanreotide Autogel® 120 mg every 14 days until 25 events (PD or death) in the panNET cohort had been observed. Additional visits were performed every 12 weeks until disease progression or death, or unacceptable toxicity or tolerability | Subjects were treated with lanreotide Autogel® 120 mg, administered as deep SC injections, every 14 days starting from Day 1 (at a reduced dosing interval) for up to 96 weeks or until disease progression, death or unacceptable toxicity or tolerability. Subjects who had not progressed at Week 96 could continue study treatment with lanreotide Autogel® 120 mg every 14 days until 25 events (PD or death) in the midgut NET cohort had been observed. Additional visits were performed every 12 weeks until disease progression or death, or unacceptable toxicity or tolerability. |
| Measure Participants | 48 | 51 |
| Median (95% Confidence Interval) [months] |
NA
|
NA
|
| Title | Objective Response Rate (ORR) |
|---|---|
| Description | The ORR was defined as the percentage of subjects who achieve either complete response (CR) or partial response (PR) according to RECIST v1.0 criteria. ORR was evaluated every 12 weeks and results are presented for each cohort. |
| Time Frame | Weeks 12, 24, 36, 48, 60 (for both cohorts) and Weeks 72, 84, and 96 (for midgut cohort) |
Outcome Measure Data
| Analysis Population Description |
|---|
| The FAS included all subjects who received at least one dose of lanreotide Autogel® 120 mg every 14 days during the study. |
| Arm/Group Title | PanNET Cohort | Midgut NET Cohort |
|---|---|---|
| Arm/Group Description | Subjects were treated with lanreotide Autogel® 120 mg, administered as SC injections, every 14 days starting from Day 1 (at a reduced dosing interval) for up to 48 weeks or until disease progression, death or unacceptable toxicity or tolerability. Subjects who had not progressed at Week 48 could continue study treatment with lanreotide Autogel® 120 mg every 14 days until 25 events (PD or death) in the panNET cohort had been observed. Additional visits were performed every 12 weeks until disease progression or death, or unacceptable toxicity or tolerability. | Subjects were treated with lanreotide Autogel® 120 mg, administered as deep SC injections, every 14 days starting from Day 1 (at a reduced dosing interval) for up to 96 weeks or until disease progression, death or unacceptable toxicity or tolerability. Subjects who had not progressed at Week 96 could continue study treatment with lanreotide Autogel® 120 mg every 14 days until 25 events (PD or death) in the midgut NET cohort had been observed. Additional visits were performed every 12 weeks until disease progression or death, or unacceptable toxicity or tolerability. |
| Measure Participants | 48 | 51 |
| Week 12 |
0.0
|
0.0
|
| Week 24 |
0.0
|
0.0
|
| Week 36 |
0.0
|
0.0
|
| Week 48 |
0.0
|
0.0
|
| Week 60 |
0.0
|
2.0
|
| Week 72 |
3.9
|
|
| Week 84 |
2.0
|
|
| Week 96 |
2.0
|
| Title | Disease Control Rate (DCR) |
|---|---|
| Description | The DCR was defined as the percentage of subjects who achieved CR plus PR plus Stable Disease (SD), evaluated according to RECIST v1.0 criteria. The DCR at Weeks 24 and 48 is presented for each cohort. |
| Time Frame | Weeks 24 and 48 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The FAS included all subjects who received at least one dose of lanreotide Autogel® 120 mg every 14 days during the study. |
| Arm/Group Title | PanNET Cohort | Midgut NET Cohort |
|---|---|---|
| Arm/Group Description | Subjects were treated with lanreotide Autogel® 120 mg, administered as SC injections, every 14 days starting from Day 1 (at a reduced dosing interval) for up to 48 weeks or until disease progression, death or unacceptable toxicity or tolerability. Subjects who had not progressed at Week 48 could continue study treatment with lanreotide Autogel® 120 mg every 14 days until 25 events (PD or death) in the panNET cohort had been observed. Additional visits were performed every 12 weeks until disease progression or death, or unacceptable toxicity or tolerability. | Subjects were treated with lanreotide Autogel® 120 mg, administered as deep SC injections, every 14 days starting from Day 1 (at a reduced dosing interval) for up to 96 weeks or until disease progression, death or unacceptable toxicity or tolerability. Subjects who had not progressed at Week 96 could continue study treatment with lanreotide Autogel® 120 mg every 14 days until 25 events (PD or death) in the midgut NET cohort had been observed. Additional visits were performed every 12 weeks until disease progression or death, or unacceptable toxicity or tolerability. |
| Measure Participants | 48 | 51 |
| Week 24 |
43.8
|
58.8
|
| Week 48 |
22.9
|
33.3
|
| Title | Best Overall Response Rate |
|---|---|
| Description | Best overall response was defined as the best response recorded from the initiation of treatment until disease progression, according to RECIST v1.0 evaluation. The percentage of subjects in each response category and those who were non-evaluable (i.e. with no tumour assessment after the start of study treatment) throughout the study are presented for each cohort. |
| Time Frame | From Day 1 up to Week 60 for the panNET cohort and Week 103 for the midgut NET cohort |
Outcome Measure Data
| Analysis Population Description |
|---|
| The FAS included all subjects who received at least one dose of lanreotide Autogel® 120 mg every 14 days during the study. |
| Arm/Group Title | PanNET Cohort | Midgut NET Cohort |
|---|---|---|
| Arm/Group Description | Subjects were treated with lanreotide Autogel® 120 mg, administered as SC injections, every 14 days starting from Day 1 (at a reduced dosing interval) for up to 48 weeks or until disease progression, death or unacceptable toxicity or tolerability. Subjects who had not progressed at Week 48 could continue study treatment with lanreotide Autogel® 120 mg every 14 days until 25 events (PD or death) in the panNET cohort had been observed. Additional visits were performed every 12 weeks until disease progression or death, or unacceptable toxicity or tolerability. | Subjects were treated with lanreotide Autogel® 120 mg, administered as deep SC injections, every 14 days starting from Day 1 (at a reduced dosing interval) for up to 96 weeks or until disease progression, death or unacceptable toxicity or tolerability. Subjects who had not progressed at Week 96 could continue study treatment with lanreotide Autogel® 120 mg every 14 days until 25 events (PD or death) in the midgut NET cohort had been observed. Additional visits were performed every 12 weeks until disease progression or death, or unacceptable toxicity or tolerability. |
| Measure Participants | 48 | 51 |
| CR |
0.0
|
0.0
|
| PR |
0.0
|
3.9
|
| SD |
66.7
|
68.6
|
| PD |
31.3
|
23.5
|
| Not evaluable |
0.0
|
2.0
|
| Title | Median Duration of Stable Disease |
|---|---|
| Description | Median duration of SD was the time from first injection of lanreotide Autogel® 120 mg every 14 days until the first occurrence of PD by central assessment. Disease progression was assessed by tumour response evaluation according to RECIST v1.0, every 12 weeks, measured using the same imaging technique (CT scan or MRI) for each subject throughout the study. Median duration of stable disease was estimated using the Kaplan Meier method for each cohort. |
| Time Frame | From Day 1 up to Week 60 for the panNET cohort and Week 103 for the midgut NET cohort |
Outcome Measure Data
| Analysis Population Description |
|---|
| The FAS included all subjects who received at least one dose of lanreotide Autogel® 120 mg every 14 days during the study. |
| Arm/Group Title | PanNET Cohort | Midgut NET Cohort |
|---|---|---|
| Arm/Group Description | Subjects were treated with lanreotide Autogel® 120 mg, administered as SC injections, every 14 days starting from Day 1 (at a reduced dosing interval) for up to 48 weeks or until disease progression, death or unacceptable toxicity or tolerability. Subjects who had not progressed at Week 48 could continue study treatment with lanreotide Autogel® 120 mg every 14 days until 25 events (PD or death) in the panNET cohort had been observed. Additional visits were performed every 12 weeks until disease progression or death, or unacceptable toxicity or tolerability. | Subjects were treated with lanreotide Autogel® 120 mg, administered as deep SC injections, every 14 days starting from Day 1 (at a reduced dosing interval) for up to 96 weeks or until disease progression, death or unacceptable toxicity or tolerability. Subjects who had not progressed at Week 96 could continue study treatment with lanreotide Autogel® 120 mg every 14 days until 25 events (PD or death) in the midgut NET cohort had been observed. Additional visits were performed every 12 weeks until disease progression or death, or unacceptable toxicity or tolerability. |
| Measure Participants | 48 | 51 |
| Median (95% Confidence Interval) [months] |
8.3
|
13.8
|
| Title | Factors Associated With PFS |
|---|---|
| Description | A univariate cox proportional hazards model was used to assess whether the following factors were associated with PFS: Hepatic tumour load: >25% versus reference ≤25% Tumour Grade: Grade 2 versus reference Grade 1, Previous surgery of the primary tumour: No versus reference Yes, Proliferation index Ki67: ≥10% versus reference <10% Duration of treatment with lanreotide Autogel® 120 mg every 28 days by category: ≥median value versus reference <median value, Age by category: ≥65 years versus reference <65 years, Time from diagnosis to study entry by category: ≥3 years versus reference <3 years, Time interval between the two CT scans (pre-screening/screening): ≥12 months versus reference <12 months and Symptoms (diarrhoea or flushing at baseline): No versus reference Yes. Each factor was assessed for its importance in the Cox model for PFS in a univariate fashion. |
| Time Frame | Screening/Baseline (Day 1) |
Outcome Measure Data
| Analysis Population Description |
|---|
| The FAS included all subjects who received at least one dose of lanreotide Autogel® 120 mg every 14 days during the study. |
| Arm/Group Title | PanNET Cohort | Midgut NET Cohort |
|---|---|---|
| Arm/Group Description | Subjects were treated with lanreotide Autogel® 120 mg, administered as SC injections, every 14 days starting from Day 1 (at a reduced dosing interval) for up to 48 weeks or until disease progression, death or unacceptable toxicity or tolerability. Subjects who had not progressed at Week 48 could continue study treatment with lanreotide Autogel® 120 mg every 14 days until 25 events (PD or death) in the panNET cohort had been observed. Additional visits were performed every 12 weeks until disease progression or death, or unacceptable toxicity or tolerability. | Subjects were treated with lanreotide Autogel® 120 mg, administered as deep SC injections, every 14 days starting from Day 1 (at a reduced dosing interval) for up to 96 weeks or until disease progression, death or unacceptable toxicity or tolerability. Subjects who had not progressed at Week 96 could continue study treatment with lanreotide Autogel® 120 mg every 14 days until 25 events (PD or death) in the midgut NET cohort had been observed. Additional visits were performed every 12 weeks until disease progression or death, or unacceptable toxicity or tolerability. |
| Measure Participants | 48 | 51 |
| Hepatic tumour load: >25% Vs ≤25% |
0.96
|
1.54
|
| Tumour Grade: 2 Vs 1 |
0.68
|
0.90
|
| Previous surgery: No Vs Yes |
1.04
|
2.14
|
| Ki67: ≥10% Vs <10% |
3.60
|
2.26
|
| Duration of treatment with lanreotide Autogel® 120 mg every 28 days: ≥median Vs <median |
0.68
|
0.76
|
| Age: ≥65 years Vs <65 years |
1.55
|
1.15
|
| Time from diagnosis: ≥3 years Vs <3 years |
0.49
|
0.94
|
| Time between CT scans: ≥12 months Vs <12 months |
0.47
|
0.72
|
| Symptoms: No Vs Yes |
2.55
|
1.32
|
| Title | Mean Change From Baseline in Number of Stools and Flushing Episodes |
|---|---|
| Description | Symptom control was measured by the total number of stools (diarrhoea) and flushing episodes during the 7 days prior to the visit, reported orally by the subject to the investigator. The mean change from baseline in number of stools and flushing episodes reported at each visit is presented for each cohort. |
| Time Frame | Baseline (Day 1), Weeks 8,12, 48 and end of study (approximately 64 weeks for panNET cohort and 108 weeks for midgut NET cohort) |
Outcome Measure Data
| Analysis Population Description |
|---|
| The FAS included all subjects who received at least one dose of lanreotide Autogel® 120 mg every 14 days during the study. Numbers analysed at each time point correspond to the number of subjects reporting episodes in the 7 days prior to the visit. |
| Arm/Group Title | PanNET Cohort | Midgut NET Cohort |
|---|---|---|
| Arm/Group Description | Subjects were treated with lanreotide Autogel® 120 mg, administered as SC injections, every 14 days starting from Day 1 (at a reduced dosing interval) for up to 48 weeks or until disease progression, death or unacceptable toxicity or tolerability. Subjects who had not progressed at Week 48 could continue study treatment with lanreotide Autogel® 120 mg every 14 days until 25 events (PD or death) in the panNET cohort had been observed. Additional visits were performed every 12 weeks until disease progression or death, or unacceptable toxicity or tolerability. | Subjects were treated with lanreotide Autogel® 120 mg, administered as deep SC injections, every 14 days starting from Day 1 (at a reduced dosing interval) for up to 96 weeks or until disease progression, death or unacceptable toxicity or tolerability. Subjects who had not progressed at Week 96 could continue study treatment with lanreotide Autogel® 120 mg every 14 days until 25 events (PD or death) in the midgut NET cohort had been observed. Additional visits were performed every 12 weeks until disease progression or death, or unacceptable toxicity or tolerability. |
| Measure Participants | 48 | 51 |
| Stools - Week 8 |
1.0
(5.5)
|
-1.0
(8.2)
|
| Stools - Week 12 |
-1.2
(7.9)
|
0.7
(2.5)
|
| Stools - Week 48 |
-1.0
(0.0)
|
3.4
(4.8)
|
| Stools - End of Study |
0.5
(5.4)
|
-1.2
(12.2)
|
| Flushing - Week 8 |
0.7
(2.1)
|
-3.3
(8.3)
|
| Flushing - Week 12 |
-1.0
(0.0)
|
1.5
(10.0)
|
| Flushing - Week 48 |
-1.0
(0.0)
|
-1.5
(2.1)
|
| Flushing - End of Study |
0.0
(1.4)
|
-0.5
(6.2)
|
| Title | Mean Change From Baseline in QoL Measured Using EORTC, QLQ-C30 v3.0 (Global Health Status Sub-score) |
|---|---|
| Description | Subjects were instructed to complete the 30 questions in the EORTC-QLQ-C30 v3.0 questionnaire at baseline and every 12 weeks throughout the study. The global health status sub-score was assessed using the last 2 questions which represented subject's assessment of overall health & QoL. Each question was coded on a 7-point scale (1=very poor to 7=excellent). The sub-score was transformed to range from 0-100, with a high score for global health status representing a high QoL. The mean change from baseline in the transformed global health status are presented for the end of study/early withdrawal visit, with a positive change indicating an improvement in QoL. |
| Time Frame | Baseline (Day 1) and end of study (approximately 64 weeks for panNET cohort and 108 weeks for midgut NET (and overall) cohort) |
Outcome Measure Data
| Analysis Population Description |
|---|
| The FAS included all subjects who received at least one dose of lanreotide Autogel® 120 mg every 14 days during the study. Only subjects with data available for analysis are presented. |
| Arm/Group Title | PanNET Cohort | Midgut NET Cohort | Overall |
|---|---|---|---|
| Arm/Group Description | Subjects were treated with lanreotide Autogel® 120 mg, administered as SC injections, every 14 days starting from Day 1 (at a reduced dosing interval) for up to 48 weeks or until disease progression, death or unacceptable toxicity or tolerability. Subjects who had not progressed at Week 48 could continue study treatment with lanreotide Autogel® 120 mg every 14 days until 25 events (PD or death) in the panNET cohort had been observed. Additional visits were performed every 12 weeks until disease progression or death, or unacceptable toxicity or tolerability. | Subjects were treated with lanreotide Autogel® 120 mg, administered as deep SC injections, every 14 days starting from Day 1 (at a reduced dosing interval) for up to 96 weeks or until disease progression, death or unacceptable toxicity or tolerability. Subjects who had not progressed at Week 96 could continue study treatment with lanreotide Autogel® 120 mg every 14 days until 25 events (PD or death) in the midgut NET cohort had been observed. Additional visits were performed every 12 weeks until disease progression or death, or unacceptable toxicity or tolerability. | All subjects who received at least one dose of lanreotide Autogel® 120 mg every 14 days during the study. |
| Measure Participants | 22 | 25 | 47 |
| Mean (Standard Deviation) [score on a scale] |
-0.38
(15.32)
|
-1.33
(17.13)
|
-0.89
(16.14)
|
| Title | Mean Change From Baseline in EQ-5D-5L v1.0 Questionnaire (Descriptive System) |
|---|---|
| Description | Subjects were instructed to complete the EQ-5D-5L descriptive system at baseline and every 12 weeks throughout the study. The EQ-5D-5L descriptive system comprised the following 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension had 5 levels: no problems, slight problems, moderate problems, severe problems, extreme problems. The EQ-5D-5L health states, defined by the EQ-5D-5L descriptive system, was converted into a single index value with scores ranging from 0 (no problems) to 1 (extreme problems). The mean change from baseline at the end of study/early withdrawal visit is presented with a positive change from baseline in the index values indicating a worsening of symptoms. |
| Time Frame | Baseline (Day 1) and end of study (approximately 64 weeks for panNET cohort and 108 weeks for midgut NET (and overall) cohort) |
Outcome Measure Data
| Analysis Population Description |
|---|
| The FAS included all subjects who received at least one dose of lanreotide Autogel® 120 mg every 14 days during the study. Only subjects with data available for analysis are presented. |
| Arm/Group Title | PanNET Cohort | Midgut NET Cohort | Overall |
|---|---|---|---|
| Arm/Group Description | Subjects were treated with lanreotide Autogel® 120 mg, administered as SC injections, every 14 days starting from Day 1 (at a reduced dosing interval) for up to 48 weeks or until disease progression, death or unacceptable toxicity or tolerability. Subjects who had not progressed at Week 48 could continue study treatment with lanreotide Autogel® 120 mg every 14 days until 25 events (PD or death) in the panNET cohort had been observed. Additional visits were performed every 12 weeks until disease progression or death, or unacceptable toxicity or tolerability. | Subjects were treated with lanreotide Autogel® 120 mg, administered as deep SC injections, every 14 days starting from Day 1 (at a reduced dosing interval) for up to 96 weeks or until disease progression, death or unacceptable toxicity or tolerability. Subjects who had not progressed at Week 96 could continue study treatment with lanreotide Autogel® 120 mg every 14 days until 25 events (PD or death) in the midgut NET cohort had been observed. Additional visits were performed every 12 weeks until disease progression or death, or unacceptable toxicity or tolerability. | All subjects who received at least one dose of lanreotide Autogel® 120 mg every 14 days during the study. |
| Measure Participants | 22 | 21 | 43 |
| Mean (Standard Deviation) [Index value] |
-0.04
(0.12)
|
0.00
(0.11)
|
-0.02
(0.12)
|
| Title | Mean Change From Baseline in EQ-5D-5L v1.0 Questionnaire (VAS) |
|---|---|
| Description | Subjects were instructed to complete the EQ-5D-5L VAS at baseline and every 12 weeks throughout the study. The EQ-5D-5L VAS recorded the subject's self-rated health on a vertical VAS which is numbered from 0 (worst health state) to 100 (best health state). The mean change from baseline at the end of study/early withdrawal visit is presented with a positive change in the VAS indicating an improvement in symptoms. |
| Time Frame | Baseline (Day 1) and end of study (approximately 64 weeks for panNET cohort and 108 weeks for midgut NET (and overall) cohort) |
Outcome Measure Data
| Analysis Population Description |
|---|
| The FAS included all subjects who received at least one dose of lanreotide Autogel® 120 mg every 14 days during the study. Only subjects with data available for analysis are presented. |
| Arm/Group Title | PanNET Cohort | Midgut NET Cohort | Overall |
|---|---|---|---|
| Arm/Group Description | Subjects were treated with lanreotide Autogel® 120 mg, administered as SC injections, every 14 days starting from Day 1 (at a reduced dosing interval) for up to 48 weeks or until disease progression, death or unacceptable toxicity or tolerability. Subjects who had not progressed at Week 48 could continue study treatment with lanreotide Autogel® 120 mg every 14 days until 25 events (PD or death) in the panNET cohort had been observed. Additional visits were performed every 12 weeks until disease progression or death, or unacceptable toxicity or tolerability. | Subjects were treated with lanreotide Autogel® 120 mg, administered as deep SC injections, every 14 days starting from Day 1 (at a reduced dosing interval) for up to 96 weeks or until disease progression, death or unacceptable toxicity or tolerability. Subjects who had not progressed at Week 96 could continue study treatment with lanreotide Autogel® 120 mg every 14 days until 25 events (PD or death) in the midgut NET cohort had been observed. Additional visits were performed every 12 weeks until disease progression or death, or unacceptable toxicity or tolerability. | All subjects who received at least one dose of lanreotide Autogel® 120 mg every 14 days during the study. |
| Measure Participants | 21 | 21 | 42 |
| Mean (Standard Deviation) [score on a scale] |
-1.90
(14.80)
|
-1.76
(9.34)
|
-1.83
(12.22)
|
| Title | Mean Change From Baseline in QoL Questionnaire Gastrointestinal Neuroendocrine Tumour 21 (QLQ-GI.NET21; 2006) |
|---|---|
| Description | Subjects were asked to complete the EORTC QLQ-GI.NET21 module which comprised 21 questions that used a 4-point scale (1 = Not at all, 2 = A little, 3 = Quite a bit, 4 = Very much) to evaluate 3 defined multi-item symptom scales (endocrine, gastrointestinal and treatment related side effects), 2 single item symptoms (bone/muscle pain and concern about weight loss), 2 psychosocial scales (social function and disease-related worries) and 2 other single items (sexuality and communication). Answers were converted into grading scale, with values between 0 and 100. Each individual sub-score was transformed to range from 0 to 100. The mean change from baseline at the end of study/early withdrawal visit is presented with a higher score representing more or worse problems. |
| Time Frame | Baseline (Day 1) and end of study (approximately 64 weeks for panNET cohort and 108 weeks for midgut NET (and overall) cohort) |
Outcome Measure Data
| Analysis Population Description |
|---|
| The FAS included all subjects who received at least one dose of lanreotide Autogel® 120 mg every 14 days during the study. Only subjects with data available for analysis are presented. |
| Arm/Group Title | PanNET Cohort | Midgut NET Cohort | Overall |
|---|---|---|---|
| Arm/Group Description | Subjects were treated with lanreotide Autogel® 120 mg, administered as SC injections, every 14 days starting from Day 1 (at a reduced dosing interval) for up to 48 weeks or until disease progression, death or unacceptable toxicity or tolerability. Subjects who had not progressed at Week 48 could continue study treatment with lanreotide Autogel® 120 mg every 14 days until 25 events (PD or death) in the panNET cohort had been observed. Additional visits were performed every 12 weeks until disease progression or death, or unacceptable toxicity or tolerability. | Subjects were treated with lanreotide Autogel® 120 mg, administered as deep SC injections, every 14 days starting from Day 1 (at a reduced dosing interval) for up to 96 weeks or until disease progression, death or unacceptable toxicity or tolerability. Subjects who had not progressed at Week 96 could continue study treatment with lanreotide Autogel® 120 mg every 14 days until 25 events (PD or death) in the midgut NET cohort had been observed. Additional visits were performed every 12 weeks until disease progression or death, or unacceptable toxicity or tolerability. | All subjects who received at least one dose of lanreotide Autogel® 120 mg every 14 days during the study. |
| Measure Participants | 48 | 51 | 99 |
| Endocrine Symptoms |
-0.53
(11.37)
|
-5.09
(17.33)
|
-2.96
(14.87)
|
| Gastrointestinal Symptoms |
-3.49
(14.24)
|
-2.78
(15.96)
|
-3.11
(15.02)
|
| Treatment Related Symptoms |
5.93
(15.64)
|
-3.47
(14.47)
|
1.08
(15.54)
|
| Social Function |
-0.79
(13.41)
|
-9.49
(18.20)
|
-5.43
(16.56)
|
| Disease Related Worries |
3.17
(15.47)
|
-0.93
(27.40)
|
0.99
(22.48)
|
| Muscle/Bone Pain |
-1.67
(33.29)
|
0.00
(36.78)
|
-0.76
(34.84)
|
| Sexual Function |
2.38
(15.82)
|
-2.78
(26.43)
|
0.00
(21.08)
|
| Information/Communication Function |
7.94
(29.64)
|
-2.90
(9.60)
|
2.27
(22.04)
|
| Body Image |
0.00
(15.29)
|
-7.58
(28.97)
|
-3.97
(23.52)
|
| Title | Mean Change From Baseline in Nonspecific Tumour Biomarkers |
|---|---|
| Description | Nonspecific tumour peptide biomarkers (chromogranin A [CgA], neuron specific enolase [NSE] and plasma/urinary 5-hydroxyindoleacetic acid [5-HIAA]) were evaluated in both pancreas and midgut subjects at baseline and Week 12 and every 12 weeks thereafter. At all scheduled visits, except baseline, plasma/urinary 5-HIAA was only performed in subjects with symptoms of carcinoid syndrome (diarrhoea and/or flushing) or if urinary 5-HIAA was elevated (above upper limit of normal [ULN]) at baseline. Mean change from baseline values were normalised by the ULN (xULN) and are presented for each cohort. |
| Time Frame | Baseline (Day 1) and end of study (approximately 64 weeks for panNET cohort and 108 weeks for midgut NET cohort) |
Outcome Measure Data
| Analysis Population Description |
|---|
| The FAS included all subjects who received at least one dose of lanreotide Autogel® 120 mg every 14 days during the study. Only subjects with data available for analysis are presented. |
| Arm/Group Title | PanNET Cohort | Midgut NET Cohort |
|---|---|---|
| Arm/Group Description | Subjects were treated with lanreotide Autogel® 120 mg, administered as SC injections, every 14 days starting from Day 1 (at a reduced dosing interval) for up to 48 weeks or until disease progression, death or unacceptable toxicity or tolerability. Subjects who had not progressed at Week 48 could continue study treatment with lanreotide Autogel® 120 mg every 14 days until 25 events (PD or death) in the panNET cohort had been observed. Additional visits were performed every 12 weeks until disease progression or death, or unacceptable toxicity or tolerability. | Subjects were treated with lanreotide Autogel® 120 mg, administered as deep SC injections, every 14 days starting from Day 1 (at a reduced dosing interval) for up to 96 weeks or until disease progression, death or unacceptable toxicity or tolerability. Subjects who had not progressed at Week 96 could continue study treatment with lanreotide Autogel® 120 mg every 14 days until 25 events (PD or death) in the midgut NET cohort had been observed. Additional visits were performed every 12 weeks until disease progression or death, or unacceptable toxicity or tolerability. |
| Measure Participants | 48 | 51 |
| CgA |
0.205
(1.258)
|
0.370
(1.843)
|
| NSE |
0.03
(1.00)
|
-0.49
(1.86)
|
| Plasma 5-HIAA |
-0.42
(1.44)
|
3.90
(7.39)
|
| Title | Mean Change From Baseline in PanNet Specific Tumour Biomarkers: Pancreatic Polypeptide, Gastrin |
|---|---|
| Description | PanNET specific tumour peptide biomarkers were evaluated in pancreas subjects at baseline. Only the tumour biomarkers that were above normal range at baseline were evaluated every 12 weeks thereafter and at the end of study visit. The mean change from baseline values in picomole/liter (pmol/L) are presented for the end of study visit. |
| Time Frame | Baseline (Day 1) and end of study (approximately 64 weeks) |
Outcome Measure Data
| Analysis Population Description |
|---|
| The FAS included all subjects who received at least one dose of lanreotide Autogel® 120 mg every 14 days during the study. Only subjects in the panNET cohort with data available for analysis are presented. |
| Arm/Group Title | PanNET Cohort |
|---|---|
| Arm/Group Description | Subjects were treated with lanreotide Autogel® 120 mg, administered as SC injections, every 14 days starting from Day 1 (at a reduced dosing interval) for up to 48 weeks or until disease progression, death or unacceptable toxicity or tolerability. Subjects who had not progressed at Week 48 could continue study treatment with lanreotide Autogel® 120 mg every 14 days until 25 events (PD or death) in the panNET cohort had been observed. Additional visits were performed every 12 weeks until disease progression or death, or unacceptable toxicity or tolerability. |
| Measure Participants | 48 |
| Pancreatic Polypeptide |
82.7
(146.7)
|
| Gastrin |
-9.8
(70.7)
|
| Title | Mean Change From Baseline in PanNet Specific Tumour Biomarkers: Glucagon |
|---|---|
| Description | PanNET specific tumour peptide biomarkers were evaluated in pancreas subjects at baseline. Only the tumour biomarkers that were above normal range at baseline were evaluated every 12 weeks thereafter and at the end of study visit. The mean change from baseline values in nanograms (ng)/L are presented for the end of study visit. |
| Time Frame | Baseline (Day 1) and end of study (approximately 64 weeks) |
Outcome Measure Data
| Analysis Population Description |
|---|
| The FAS included all subjects who received at least one dose of lanreotide Autogel® 120 mg every 14 days during the study. Only subjects in panNET cohort with data available for analysis are presented. |
| Arm/Group Title | PanNET Cohort |
|---|---|
| Arm/Group Description | Subjects were treated with lanreotide Autogel® 120 mg, administered as SC injections, every 14 days starting from Day 1 (at a reduced dosing interval) for up to 48 weeks or until disease progression, death or unacceptable toxicity or tolerability. Subjects who had not progressed at Week 48 could continue study treatment with lanreotide Autogel® 120 mg every 14 days until 25 events (PD or death) in the panNET cohort had been observed. Additional visits were performed every 12 weeks until disease progression or death, or unacceptable toxicity or tolerability. |
| Measure Participants | 4 |
| Mean (Standard Deviation) [ng/L] |
5.5
(36.4)
|
Adverse Events
| Time Frame | Treatment emergent adverse events were recorded from the first dose of lanreotide Autogel® 120 mg on Day 1 until 28 days after the last treatment. Overall time frame of up to a maximum of 64 weeks for panNET cohort and 108 weeks for midgut NET (and overall) cohort. | |||||
|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | The FAS included all subjects who received at least one dose of lanreotide Autogel® 120 mg every 14 days during the study. | |||||
| Arm/Group Title | PanNET Cohort | Midgut NET Cohort | Overall Subjects | |||
| Arm/Group Description | Subjects were treated with lanreotide Autogel® 120 mg, administered as SC injections, every 14 days starting from Day 1 (at a reduced dosing interval) for up to 48 weeks or until disease progression, death or unacceptable toxicity or tolerability. Subjects who had not progressed at Week 48 could continue study treatment with lanreotide Autogel® 120 mg every 14 days until 25 events (PD or death) in the panNET cohort had been observed. Additional visits were performed every 12 weeks until disease progression or death, or unacceptable toxicity or tolerability. | Subjects were treated with lanreotide Autogel® 120 mg, administered as deep SC injections, every 14 days starting from Day 1 (at a reduced dosing interval) for up to 96 weeks or until disease progression, death or unacceptable toxicity or tolerability. Subjects who had not progressed at Week 96 could continue study treatment with lanreotide Autogel® 120 mg every 14 days until 25 events (PD or death) in the midgut NET cohort had been observed. Additional visits were performed every 12 weeks until disease progression or death, or unacceptable toxicity or tolerability. | All subjects who received at least one dose of lanreotide Autogel® 120 mg every 14 days during the study. | |||
All Cause Mortality |
||||||
| PanNET Cohort | Midgut NET Cohort | Overall Subjects | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 1/48 (2.1%) | 3/51 (5.9%) | 4/99 (4%) | |||
Serious Adverse Events |
||||||
| PanNET Cohort | Midgut NET Cohort | Overall Subjects | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 5/48 (10.4%) | 13/51 (25.5%) | 18/99 (18.2%) | |||
| Cardiac disorders | ||||||
| Cardiac failure | 0/48 (0%) | 0 | 1/51 (2%) | 1 | 1/99 (1%) | 1 |
| Pulseless electrical activity | 0/48 (0%) | 0 | 1/51 (2%) | 1 | 1/99 (1%) | 1 |
| Gastrointestinal disorders | ||||||
| Abdominal pain | 0/48 (0%) | 0 | 1/51 (2%) | 2 | 1/99 (1%) | 2 |
| Diarrhoea | 1/48 (2.1%) | 1 | 0/51 (0%) | 0 | 1/99 (1%) | 1 |
| Intestinal obstruction | 0/48 (0%) | 0 | 1/51 (2%) | 1 | 1/99 (1%) | 1 |
| General disorders | ||||||
| Asthenia | 0/48 (0%) | 0 | 1/51 (2%) | 1 | 1/99 (1%) | 1 |
| Chest pain | 0/48 (0%) | 0 | 1/51 (2%) | 1 | 1/99 (1%) | 1 |
| General physical health deterioration | 0/48 (0%) | 0 | 1/51 (2%) | 1 | 1/99 (1%) | 1 |
| Immune system disorders | ||||||
| Anaphylactic reaction | 1/48 (2.1%) | 1 | 0/51 (0%) | 0 | 1/99 (1%) | 1 |
| Infections and infestations | ||||||
| Peritonitis | 0/48 (0%) | 0 | 1/51 (2%) | 1 | 1/99 (1%) | 1 |
| Viral infection | 0/48 (0%) | 0 | 1/51 (2%) | 1 | 1/99 (1%) | 1 |
| Injury, poisoning and procedural complications | ||||||
| Craniocerebral injury | 0/48 (0%) | 0 | 1/51 (2%) | 1 | 1/99 (1%) | 1 |
| Fall | 1/48 (2.1%) | 1 | 0/51 (0%) | 0 | 1/99 (1%) | 1 |
| Spinal fracture | 1/48 (2.1%) | 1 | 0/51 (0%) | 0 | 1/99 (1%) | 1 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||
| Bone neoplasm | 0/48 (0%) | 0 | 1/51 (2%) | 1 | 1/99 (1%) | 1 |
| Breast cancer | 0/48 (0%) | 0 | 1/51 (2%) | 1 | 1/99 (1%) | 1 |
| Nervous system disorders | ||||||
| Spinal cord compression | 0/48 (0%) | 0 | 1/51 (2%) | 1 | 1/99 (1%) | 1 |
| Syncope | 1/48 (2.1%) | 1 | 0/51 (0%) | 0 | 1/99 (1%) | 1 |
| Respiratory, thoracic and mediastinal disorders | ||||||
| Pulmonary embolism | 1/48 (2.1%) | 1 | 2/51 (3.9%) | 3 | 3/99 (3%) | 4 |
| Vascular disorders | ||||||
| Hypotension | 0/48 (0%) | 0 | 1/51 (2%) | 1 | 1/99 (1%) | 1 |
Other (Not Including Serious) Adverse Events |
||||||
| PanNET Cohort | Midgut NET Cohort | Overall Subjects | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 41/48 (85.4%) | 47/51 (92.2%) | 88/99 (88.9%) | |||
| Blood and lymphatic system disorders | ||||||
| Lymphopenia | 1/48 (2.1%) | 1 | 0/51 (0%) | 0 | 1/99 (1%) | 1 |
| Monocytopenia | 1/48 (2.1%) | 1 | 0/51 (0%) | 0 | 1/99 (1%) | 1 |
| Cardiac disorders | ||||||
| Arrhythmia | 1/48 (2.1%) | 1 | 0/51 (0%) | 0 | 1/99 (1%) | 1 |
| Cardiac failure | 0/48 (0%) | 0 | 1/51 (2%) | 2 | 1/99 (1%) | 2 |
| Heart valve incompetence | 0/48 (0%) | 0 | 1/51 (2%) | 1 | 1/99 (1%) | 1 |
| Palpitations | 1/48 (2.1%) | 1 | 0/51 (0%) | 0 | 1/99 (1%) | 1 |
| Right ventricular failure | 0/48 (0%) | 0 | 1/51 (2%) | 1 | 1/99 (1%) | 1 |
| Tachycardia | 1/48 (2.1%) | 1 | 0/51 (0%) | 0 | 1/99 (1%) | 1 |
| Tricuspid valve disease | 0/48 (0%) | 0 | 1/51 (2%) | 1 | 1/99 (1%) | 1 |
| Ear and labyrinth disorders | ||||||
| Deafness | 1/48 (2.1%) | 1 | 0/51 (0%) | 0 | 1/99 (1%) | 1 |
| Deafness unilateral | 1/48 (2.1%) | 1 | 0/51 (0%) | 0 | 1/99 (1%) | 1 |
| Ear pain | 0/48 (0%) | 0 | 1/51 (2%) | 1 | 1/99 (1%) | 1 |
| Hypoacusis | 1/48 (2.1%) | 1 | 0/51 (0%) | 0 | 1/99 (1%) | 1 |
| Vertigo | 0/48 (0%) | 0 | 1/51 (2%) | 2 | 1/99 (1%) | 2 |
| Vertigo positional | 1/48 (2.1%) | 1 | 0/51 (0%) | 0 | 1/99 (1%) | 1 |
| Eye disorders | ||||||
| Diplopia | 0/48 (0%) | 0 | 1/51 (2%) | 1 | 1/99 (1%) | 1 |
| Dry eye | 0/48 (0%) | 0 | 1/51 (2%) | 1 | 1/99 (1%) | 1 |
| Eye pain | 0/48 (0%) | 0 | 1/51 (2%) | 1 | 1/99 (1%) | 1 |
| Eye pruritus | 0/48 (0%) | 0 | 1/51 (2%) | 1 | 1/99 (1%) | 1 |
| Glaucoma | 0/48 (0%) | 0 | 1/51 (2%) | 1 | 1/99 (1%) | 1 |
| Ocular hyperaemia | 0/48 (0%) | 0 | 2/51 (3.9%) | 2 | 2/99 (2%) | 2 |
| Gastrointestinal disorders | ||||||
| Abdominal discomfort | 0/48 (0%) | 0 | 1/51 (2%) | 1 | 1/99 (1%) | 1 |
| Abdominal distension | 0/48 (0%) | 0 | 6/51 (11.8%) | 7 | 6/99 (6.1%) | 7 |
| Abdominal pain | 7/48 (14.6%) | 13 | 12/51 (23.5%) | 16 | 19/99 (19.2%) | 29 |
| Abdominal pain lower | 1/48 (2.1%) | 1 | 1/51 (2%) | 1 | 2/99 (2%) | 2 |
| Abdominal pain upper | 2/48 (4.2%) | 2 | 6/51 (11.8%) | 7 | 8/99 (8.1%) | 9 |
| Anal incontinence | 1/48 (2.1%) | 1 | 0/51 (0%) | 0 | 1/99 (1%) | 1 |
| Anorectal discomfort | 0/48 (0%) | 0 | 1/51 (2%) | 1 | 1/99 (1%) | 1 |
| Ascites | 0/48 (0%) | 0 | 2/51 (3.9%) | 2 | 2/99 (2%) | 2 |
| Constipation | 2/48 (4.2%) | 3 | 2/51 (3.9%) | 3 | 4/99 (4%) | 6 |
| Diarrhoea | 14/48 (29.2%) | 20 | 27/51 (52.9%) | 35 | 41/99 (41.4%) | 55 |
| Dry mouth | 1/48 (2.1%) | 1 | 0/51 (0%) | 0 | 1/99 (1%) | 1 |
| Dyspepsia | 0/48 (0%) | 0 | 2/51 (3.9%) | 3 | 2/99 (2%) | 3 |
| Faeces discoloured | 0/48 (0%) | 0 | 1/51 (2%) | 1 | 1/99 (1%) | 1 |
| Flatulence | 1/48 (2.1%) | 1 | 6/51 (11.8%) | 8 | 7/99 (7.1%) | 9 |
| Gastrooesophageal reflux disease | 1/48 (2.1%) | 1 | 2/51 (3.9%) | 2 | 3/99 (3%) | 3 |
| Gingival bleeding | 1/48 (2.1%) | 1 | 0/51 (0%) | 0 | 1/99 (1%) | 1 |
| Gingival pain | 1/48 (2.1%) | 1 | 1/51 (2%) | 1 | 2/99 (2%) | 2 |
| Glossodynia | 0/48 (0%) | 0 | 1/51 (2%) | 1 | 1/99 (1%) | 1 |
| Haematochezia | 1/48 (2.1%) | 1 | 0/51 (0%) | 0 | 1/99 (1%) | 1 |
| Hernial eventration | 0/48 (0%) | 0 | 1/51 (2%) | 1 | 1/99 (1%) | 1 |
| Inguinal hernia | 0/48 (0%) | 0 | 1/51 (2%) | 1 | 1/99 (1%) | 1 |
| Nausea | 5/48 (10.4%) | 5 | 6/51 (11.8%) | 9 | 11/99 (11.1%) | 14 |
| Oral pain | 0/48 (0%) | 0 | 1/51 (2%) | 1 | 1/99 (1%) | 1 |
| Pancreatic failure | 0/48 (0%) | 0 | 1/51 (2%) | 1 | 1/99 (1%) | 1 |
| Proctalgia | 0/48 (0%) | 0 | 1/51 (2%) | 1 | 1/99 (1%) | 1 |
| Steatorrhoea | 2/48 (4.2%) | 2 | 3/51 (5.9%) | 3 | 5/99 (5.1%) | 5 |
| Stomatitis | 1/48 (2.1%) | 1 | 1/51 (2%) | 1 | 2/99 (2%) | 2 |
| Toothache | 1/48 (2.1%) | 1 | 0/51 (0%) | 0 | 1/99 (1%) | 1 |
| Vomiting | 6/48 (12.5%) | 9 | 4/51 (7.8%) | 4 | 10/99 (10.1%) | 13 |
| Haemorrhoids | 1/48 (2.1%) | 1 | 1/51 (2%) | 1 | 2/99 (2%) | 2 |
| General disorders | ||||||
| Asthenia | 4/48 (8.3%) | 24 | 4/51 (7.8%) | 5 | 8/99 (8.1%) | 29 |
| Chest pain | 0/48 (0%) | 0 | 3/51 (5.9%) | 3 | 3/99 (3%) | 3 |
| Fatigue | 7/48 (14.6%) | 8 | 8/51 (15.7%) | 11 | 15/99 (15.2%) | 19 |
| Gait disturbance | 0/48 (0%) | 0 | 1/51 (2%) | 1 | 1/99 (1%) | 1 |
| Hunger | 0/48 (0%) | 0 | 1/51 (2%) | 1 | 1/99 (1%) | 1 |
| Influenza like illness | 1/48 (2.1%) | 1 | 3/51 (5.9%) | 3 | 4/99 (4%) | 4 |
| Injection site bruising | 1/48 (2.1%) | 1 | 0/51 (0%) | 0 | 1/99 (1%) | 1 |
| Injection site pain | 0/48 (0%) | 0 | 1/51 (2%) | 1 | 1/99 (1%) | 1 |
| Malaise | 1/48 (2.1%) | 1 | 2/51 (3.9%) | 2 | 3/99 (3%) | 3 |
| Medical device site pain | 1/48 (2.1%) | 1 | 0/51 (0%) | 0 | 1/99 (1%) | 1 |
| Oedema peripheral | 2/48 (4.2%) | 2 | 2/51 (3.9%) | 2 | 4/99 (4%) | 4 |
| Pain | 0/48 (0%) | 0 | 1/51 (2%) | 1 | 1/99 (1%) | 1 |
| Peripheral swelling | 0/48 (0%) | 0 | 3/51 (5.9%) | 3 | 3/99 (3%) | 3 |
| Polyp | 0/48 (0%) | 0 | 1/51 (2%) | 1 | 1/99 (1%) | 1 |
| Pyrexia | 2/48 (4.2%) | 2 | 2/51 (3.9%) | 5 | 4/99 (4%) | 7 |
| Hepatobiliary disorders | ||||||
| Bile duct stone | 0/48 (0%) | 0 | 1/51 (2%) | 1 | 1/99 (1%) | 1 |
| Cholelithiasis | 0/48 (0%) | 0 | 3/51 (5.9%) | 3 | 3/99 (3%) | 3 |
| Hepatic failure | 0/48 (0%) | 0 | 1/51 (2%) | 1 | 1/99 (1%) | 1 |
| Liver injury | 1/48 (2.1%) | 1 | 0/51 (0%) | 0 | 1/99 (1%) | 1 |
| Immune system disorders | ||||||
| Drug hypersensitivity | 0/48 (0%) | 0 | 1/51 (2%) | 1 | 1/99 (1%) | 1 |
| Infections and infestations | ||||||
| Bronchitis | 0/48 (0%) | 0 | 1/51 (2%) | 1 | 1/99 (1%) | 1 |
| Carbuncle | 0/48 (0%) | 0 | 1/51 (2%) | 1 | 1/99 (1%) | 1 |
| Cystitis | 2/48 (4.2%) | 2 | 1/51 (2%) | 1 | 3/99 (3%) | 3 |
| Cystitis bacterial | 0/48 (0%) | 0 | 1/51 (2%) | 1 | 1/99 (1%) | 1 |
| Diverticulitis | 0/48 (0%) | 0 | 2/51 (3.9%) | 2 | 2/99 (2%) | 2 |
| Folliculitis | 0/48 (0%) | 0 | 1/51 (2%) | 1 | 1/99 (1%) | 1 |
| Herpes zoster | 0/48 (0%) | 0 | 2/51 (3.9%) | 2 | 2/99 (2%) | 2 |
| Influenza | 2/48 (4.2%) | 2 | 3/51 (5.9%) | 6 | 5/99 (5.1%) | 8 |
| Lower respiratory tract infection | 1/48 (2.1%) | 2 | 3/51 (5.9%) | 3 | 4/99 (4%) | 5 |
| Nasopharyngitis | 7/48 (14.6%) | 7 | 5/51 (9.8%) | 6 | 12/99 (12.1%) | 13 |
| Respiratory tract infection | 0/48 (0%) | 0 | 1/51 (2%) | 1 | 1/99 (1%) | 1 |
| Tonsillitis | 1/48 (2.1%) | 1 | 0/51 (0%) | 0 | 1/99 (1%) | 1 |
| Upper respiratory tract infection | 0/48 (0%) | 0 | 1/51 (2%) | 1 | 1/99 (1%) | 1 |
| Urinary tract infection | 4/48 (8.3%) | 6 | 1/51 (2%) | 1 | 5/99 (5.1%) | 7 |
| Injury, poisoning and procedural complications | ||||||
| Fall | 0/48 (0%) | 0 | 1/51 (2%) | 1 | 1/99 (1%) | 1 |
| Incision site pain | 0/48 (0%) | 0 | 1/51 (2%) | 1 | 1/99 (1%) | 1 |
| Incisional hernia | 0/48 (0%) | 0 | 1/51 (2%) | 1 | 1/99 (1%) | 1 |
| Ligament sprain | 0/48 (0%) | 0 | 2/51 (3.9%) | 2 | 2/99 (2%) | 2 |
| Muscle strain | 0/48 (0%) | 0 | 1/51 (2%) | 1 | 1/99 (1%) | 1 |
| Post procedural complication | 1/48 (2.1%) | 1 | 0/51 (0%) | 0 | 1/99 (1%) | 1 |
| Radiation skin injury | 0/48 (0%) | 0 | 1/51 (2%) | 1 | 1/99 (1%) | 1 |
| Skin abrasion | 1/48 (2.1%) | 1 | 0/51 (0%) | 0 | 1/99 (1%) | 1 |
| Investigations | ||||||
| Alanine aminotransferase increased | 1/48 (2.1%) | 1 | 2/51 (3.9%) | 2 | 3/99 (3%) | 3 |
| Aspartate aminotransferase abnormal | 1/48 (2.1%) | 1 | 0/51 (0%) | 0 | 1/99 (1%) | 1 |
| Aspartate aminotransferase increased | 1/48 (2.1%) | 1 | 1/51 (2%) | 1 | 2/99 (2%) | 2 |
| Bacterial test positive | 0/48 (0%) | 0 | 1/51 (2%) | 1 | 1/99 (1%) | 1 |
| Blood alkaline phosphatase increased | 3/48 (6.3%) | 3 | 1/51 (2%) | 1 | 4/99 (4%) | 4 |
| Blood bilirubin increased | 0/48 (0%) | 0 | 2/51 (3.9%) | 2 | 2/99 (2%) | 2 |
| Blood chromogranin A increased | 0/48 (0%) | 0 | 1/51 (2%) | 1 | 1/99 (1%) | 1 |
| Blood creatinine increased | 1/48 (2.1%) | 1 | 0/51 (0%) | 0 | 1/99 (1%) | 1 |
| Blood glucose decreased | 0/48 (0%) | 0 | 1/51 (2%) | 1 | 1/99 (1%) | 1 |
| Blood glucose increased | 1/48 (2.1%) | 1 | 1/51 (2%) | 1 | 2/99 (2%) | 2 |
| Blood potassium increased | 1/48 (2.1%) | 1 | 0/51 (0%) | 0 | 1/99 (1%) | 1 |
| Blood triglycerides increased | 0/48 (0%) | 0 | 1/51 (2%) | 1 | 1/99 (1%) | 1 |
| Blood urea increased | 1/48 (2.1%) | 1 | 1/51 (2%) | 1 | 2/99 (2%) | 2 |
| Blood urine present | 0/48 (0%) | 0 | 1/51 (2%) | 1 | 1/99 (1%) | 1 |
| C-reactive protein increased | 0/48 (0%) | 0 | 1/51 (2%) | 1 | 1/99 (1%) | 1 |
| Gamma-glutamyltransferase abnormal | 1/48 (2.1%) | 1 | 0/51 (0%) | 0 | 1/99 (1%) | 1 |
| Gamma-glutamyltransferase decreased | 0/48 (0%) | 0 | 1/51 (2%) | 1 | 1/99 (1%) | 1 |
| Gamma-glutamyltransferase increased | 1/48 (2.1%) | 1 | 2/51 (3.9%) | 2 | 3/99 (3%) | 3 |
| Glycosylated haemoglobin increased | 1/48 (2.1%) | 1 | 0/51 (0%) | 0 | 1/99 (1%) | 1 |
| Lymphocyte count decreased | 0/48 (0%) | 0 | 1/51 (2%) | 1 | 1/99 (1%) | 1 |
| Neutrophil count decreased | 0/48 (0%) | 0 | 1/51 (2%) | 1 | 1/99 (1%) | 1 |
| Platelet count decreased | 0/48 (0%) | 0 | 1/51 (2%) | 1 | 1/99 (1%) | 1 |
| Specific gravity urine increased | 1/48 (2.1%) | 1 | 0/51 (0%) | 0 | 1/99 (1%) | 1 |
| Urine ketone body present | 2/48 (4.2%) | 2 | 0/51 (0%) | 0 | 2/99 (2%) | 2 |
| Weight decreased | 1/48 (2.1%) | 1 | 2/51 (3.9%) | 2 | 3/99 (3%) | 3 |
| Metabolism and nutrition disorders | ||||||
| Carbohydrate intolerance | 1/48 (2.1%) | 1 | 0/51 (0%) | 0 | 1/99 (1%) | 1 |
| Decreased appetite | 5/48 (10.4%) | 5 | 2/51 (3.9%) | 2 | 7/99 (7.1%) | 7 |
| Hypercholesterolaemia | 0/48 (0%) | 0 | 1/51 (2%) | 1 | 1/99 (1%) | 1 |
| Hyperglycaemia | 1/48 (2.1%) | 1 | 1/51 (2%) | 1 | 2/99 (2%) | 2 |
| Hyperkalaemia | 0/48 (0%) | 0 | 2/51 (3.9%) | 2 | 2/99 (2%) | 2 |
| Hypernatraemia | 0/48 (0%) | 0 | 1/51 (2%) | 1 | 1/99 (1%) | 1 |
| Hypertriglyceridaemia | 0/48 (0%) | 0 | 1/51 (2%) | 1 | 1/99 (1%) | 1 |
| Hyperuricaemia | 1/48 (2.1%) | 1 | 0/51 (0%) | 0 | 1/99 (1%) | 1 |
| Hypoalbuminaemia | 1/48 (2.1%) | 1 | 0/51 (0%) | 0 | 1/99 (1%) | 1 |
| Hypocalcaemia | 1/48 (2.1%) | 1 | 2/51 (3.9%) | 2 | 3/99 (3%) | 3 |
| Hypoglycaemia | 1/48 (2.1%) | 3 | 1/51 (2%) | 1 | 2/99 (2%) | 4 |
| Hypokalaemia | 0/48 (0%) | 0 | 1/51 (2%) | 1 | 1/99 (1%) | 1 |
| Hyponatraemia | 1/48 (2.1%) | 1 | 0/51 (0%) | 0 | 1/99 (1%) | 1 |
| Malnutrition | 0/48 (0%) | 0 | 1/51 (2%) | 1 | 1/99 (1%) | 1 |
| Vitamin D deficiency | 1/48 (2.1%) | 1 | 1/51 (2%) | 1 | 2/99 (2%) | 2 |
| Musculoskeletal and connective tissue disorders | ||||||
| Arthralgia | 0/48 (0%) | 0 | 5/51 (9.8%) | 7 | 5/99 (5.1%) | 7 |
| Back pain | 2/48 (4.2%) | 2 | 2/51 (3.9%) | 2 | 4/99 (4%) | 4 |
| Exostosis | 1/48 (2.1%) | 1 | 0/51 (0%) | 0 | 1/99 (1%) | 1 |
| Flank pain | 0/48 (0%) | 0 | 1/51 (2%) | 1 | 1/99 (1%) | 1 |
| Intervertebral disc degeneration | 0/48 (0%) | 0 | 1/51 (2%) | 1 | 1/99 (1%) | 1 |
| Intervertebral disc protrusion | 0/48 (0%) | 0 | 1/51 (2%) | 1 | 1/99 (1%) | 1 |
| Joint swelling | 0/48 (0%) | 0 | 3/51 (5.9%) | 5 | 3/99 (3%) | 5 |
| Mobility decreased | 1/48 (2.1%) | 1 | 0/51 (0%) | 0 | 1/99 (1%) | 1 |
| Muscle spasms | 1/48 (2.1%) | 1 | 2/51 (3.9%) | 3 | 3/99 (3%) | 4 |
| Musculoskeletal chest pain | 1/48 (2.1%) | 1 | 1/51 (2%) | 1 | 2/99 (2%) | 2 |
| Musculoskeletal discomfort | 0/48 (0%) | 0 | 1/51 (2%) | 1 | 1/99 (1%) | 1 |
| Musculoskeletal pain | 1/48 (2.1%) | 1 | 2/51 (3.9%) | 2 | 3/99 (3%) | 3 |
| Myalgia | 0/48 (0%) | 0 | 1/51 (2%) | 2 | 1/99 (1%) | 2 |
| Neck pain | 0/48 (0%) | 0 | 2/51 (3.9%) | 2 | 2/99 (2%) | 2 |
| Osteoarthritis | 1/48 (2.1%) | 1 | 1/51 (2%) | 1 | 2/99 (2%) | 2 |
| Osteoporosis | 0/48 (0%) | 0 | 1/51 (2%) | 1 | 1/99 (1%) | 1 |
| Pain in extremity | 2/48 (4.2%) | 2 | 1/51 (2%) | 2 | 3/99 (3%) | 4 |
| Periarthritis | 0/48 (0%) | 0 | 1/51 (2%) | 1 | 1/99 (1%) | 1 |
| Rheumatoid arthritis | 0/48 (0%) | 0 | 1/51 (2%) | 2 | 1/99 (1%) | 2 |
| Spinal pain | 1/48 (2.1%) | 1 | 2/51 (3.9%) | 2 | 3/99 (3%) | 3 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||
| Metastases to liver | 0/48 (0%) | 0 | 1/51 (2%) | 1 | 1/99 (1%) | 1 |
| Nervous system disorders | ||||||
| Ageusia | 1/48 (2.1%) | 1 | 0/51 (0%) | 0 | 1/99 (1%) | 1 |
| Aphasia | 0/48 (0%) | 0 | 1/51 (2%) | 2 | 1/99 (1%) | 2 |
| Balance disorder | 0/48 (0%) | 0 | 1/51 (2%) | 1 | 1/99 (1%) | 1 |
| Dizziness | 3/48 (6.3%) | 3 | 5/51 (9.8%) | 7 | 8/99 (8.1%) | 10 |
| Dizziness postural | 0/48 (0%) | 0 | 1/51 (2%) | 1 | 1/99 (1%) | 1 |
| Head discomfort | 0/48 (0%) | 0 | 1/51 (2%) | 1 | 1/99 (1%) | 1 |
| Headache | 3/48 (6.3%) | 3 | 4/51 (7.8%) | 5 | 7/99 (7.1%) | 8 |
| Lethargy | 1/48 (2.1%) | 1 | 1/51 (2%) | 1 | 2/99 (2%) | 2 |
| Poor quality sleep | 1/48 (2.1%) | 1 | 1/51 (2%) | 1 | 2/99 (2%) | 2 |
| Presyncope | 0/48 (0%) | 0 | 2/51 (3.9%) | 2 | 2/99 (2%) | 2 |
| Sciatica | 0/48 (0%) | 0 | 2/51 (3.9%) | 2 | 2/99 (2%) | 2 |
| Syncope | 1/48 (2.1%) | 1 | 0/51 (0%) | 0 | 1/99 (1%) | 1 |
| Taste disorder | 1/48 (2.1%) | 1 | 0/51 (0%) | 0 | 1/99 (1%) | 1 |
| Tremor | 1/48 (2.1%) | 1 | 2/51 (3.9%) | 2 | 3/99 (3%) | 3 |
| Psychiatric disorders | ||||||
| Acrophobia | 0/48 (0%) | 0 | 1/51 (2%) | 1 | 1/99 (1%) | 1 |
| Confusional state | 0/48 (0%) | 0 | 1/51 (2%) | 1 | 1/99 (1%) | 1 |
| Insomnia | 2/48 (4.2%) | 2 | 0/51 (0%) | 0 | 2/99 (2%) | 2 |
| Mood altered | 1/48 (2.1%) | 1 | 0/51 (0%) | 0 | 1/99 (1%) | 1 |
| Panic attack | 0/48 (0%) | 0 | 1/51 (2%) | 1 | 1/99 (1%) | 1 |
| Sleep disorder | 0/48 (0%) | 0 | 2/51 (3.9%) | 2 | 2/99 (2%) | 2 |
| Renal and urinary disorders | ||||||
| Chronic kidney disease | 0/48 (0%) | 0 | 1/51 (2%) | 1 | 1/99 (1%) | 1 |
| Dysuria | 0/48 (0%) | 0 | 2/51 (3.9%) | 2 | 2/99 (2%) | 2 |
| Haematuria | 1/48 (2.1%) | 1 | 2/51 (3.9%) | 2 | 3/99 (3%) | 3 |
| Urethral stenosis | 0/48 (0%) | 0 | 1/51 (2%) | 1 | 1/99 (1%) | 1 |
| Reproductive system and breast disorders | ||||||
| Gynaecomastia | 0/48 (0%) | 0 | 1/51 (2%) | 1 | 1/99 (1%) | 1 |
| Respiratory, thoracic and mediastinal disorders | ||||||
| Asthma | 1/48 (2.1%) | 1 | 0/51 (0%) | 0 | 1/99 (1%) | 1 |
| Cough | 3/48 (6.3%) | 3 | 3/51 (5.9%) | 3 | 6/99 (6.1%) | 6 |
| Dysphonia | 1/48 (2.1%) | 1 | 0/51 (0%) | 0 | 1/99 (1%) | 1 |
| Dyspnoea | 0/48 (0%) | 0 | 4/51 (7.8%) | 5 | 4/99 (4%) | 5 |
| Dyspnoea exertional | 1/48 (2.1%) | 1 | 2/51 (3.9%) | 2 | 3/99 (3%) | 3 |
| Increased upper airway secretion | 0/48 (0%) | 0 | 1/51 (2%) | 1 | 1/99 (1%) | 1 |
| Oropharyngeal pain | 0/48 (0%) | 0 | 2/51 (3.9%) | 2 | 2/99 (2%) | 2 |
| Orthopnoea | 0/48 (0%) | 0 | 1/51 (2%) | 1 | 1/99 (1%) | 1 |
| Productive cough | 0/48 (0%) | 0 | 1/51 (2%) | 1 | 1/99 (1%) | 1 |
| Sputum discoloured | 0/48 (0%) | 0 | 1/51 (2%) | 1 | 1/99 (1%) | 1 |
| Skin and subcutaneous tissue disorders | ||||||
| Erythema | 0/48 (0%) | 0 | 2/51 (3.9%) | 2 | 2/99 (2%) | 2 |
| Hyperhidrosis | 1/48 (2.1%) | 1 | 0/51 (0%) | 0 | 1/99 (1%) | 1 |
| Night sweats | 0/48 (0%) | 0 | 1/51 (2%) | 1 | 1/99 (1%) | 1 |
| Photosensitivity reaction | 1/48 (2.1%) | 1 | 0/51 (0%) | 0 | 1/99 (1%) | 1 |
| Pruritus | 1/48 (2.1%) | 1 | 3/51 (5.9%) | 4 | 4/99 (4%) | 5 |
| Pruritus generalised | 0/48 (0%) | 0 | 1/51 (2%) | 1 | 1/99 (1%) | 1 |
| Rash | 1/48 (2.1%) | 1 | 1/51 (2%) | 1 | 2/99 (2%) | 2 |
| Skin fissures | 0/48 (0%) | 0 | 1/51 (2%) | 1 | 1/99 (1%) | 1 |
| Skin irritation | 0/48 (0%) | 0 | 2/51 (3.9%) | 2 | 2/99 (2%) | 2 |
| Urticaria | 0/48 (0%) | 0 | 1/51 (2%) | 1 | 1/99 (1%) | 1 |
| Surgical and medical procedures | ||||||
| Injection | 0/48 (0%) | 0 | 1/51 (2%) | 1 | 1/99 (1%) | 1 |
| Vascular disorders | ||||||
| Deep vein thrombosis | 0/48 (0%) | 0 | 1/51 (2%) | 1 | 1/99 (1%) | 1 |
| Flushing | 2/48 (4.2%) | 2 | 9/51 (17.6%) | 14 | 11/99 (11.1%) | 16 |
| Haematoma | 0/48 (0%) | 0 | 1/51 (2%) | 1 | 1/99 (1%) | 1 |
| Hot flush | 0/48 (0%) | 0 | 2/51 (3.9%) | 14 | 2/99 (2%) | 14 |
| Hypertension | 2/48 (4.2%) | 2 | 9/51 (17.6%) | 9 | 11/99 (11.1%) | 11 |
| Peripheral venous disease | 0/48 (0%) | 0 | 1/51 (2%) | 1 | 1/99 (1%) | 1 |
| Venous thrombosis limb | 1/48 (2.1%) | 1 | 0/51 (0%) | 0 | 1/99 (1%) | 1 |
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | Ipsen Medical Director |
|---|---|
| Organization | Ipsen |
| Phone | see email |
| clinical.trials@ipsen.com |
Responsible Party:
Ipsen
ClinicalTrials.gov Identifier:
NCT02651987
Other Study ID Numbers:
- 8-79-52030-326
- 2014-005607-24
First Posted:
Jan 11, 2016
Last Update Posted:
Dec 30, 2020
Last Verified:
Dec 1, 2020