Efficacy and Safety Study in Pancreatic or Midgut Neuroendocrine Tumours Having Progressed Radiologically While Previously Treated With Lanreotide Autogel® 120 mg (CLARINET FORTE)

• ClinicalTrials.gov Identifier: NCT02651987
• Recruitment Status: Completed
• First Posted: January 11, 2016
• Results First Posted: December 30, 2020
• Last Update Posted: December 30, 2020
• Sponsor: Ipsen
• Information provided by (Responsible Party): Ipsen

• Study Type: Interventional
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Conditions: Pancreatic Tumours; Midgut Neuroendocrine Tumours
• Intervention: Drug: Lanreotide autogel 120 mg
• Enrollment: 99

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 Details

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
Reason Not Completed
Adverse Event	2	2
Consent Withdrawn	2	0
Local PD	0	2
Investigator Decision	1	1

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 Number of Baseline Participants		48	51	99
Baseline Analysis Population Description		The full analysis set (FAS) included all subjects who received at least one dose of lanreotide Autogel® 120 mg every 14 days during the study.
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	48 participants	51 participants	99 participants
		63.3 (10.6)	67.1 (8.2)	65.2 (9.6)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	48 participants	51 participants	99 participants
	Female	28 58.3%	22 43.1%	50 50.5%
	Male	20 41.7%	29 56.9%	49 49.5%
Race/Ethnicity, Customized [1]; Measure Type: Count of Participants; Unit of measure: Participants
Race	Number Analyzed	36 participants	38 participants	74 participants
	Asian	0 0.0%	1 2.6%	1 1.4%
	White	35 97.2%	37 97.4%	72 97.3%
	Other	1 2.8%	0 0.0%	1 1.4%
		[1] Measure Analysis Population Description: French local regulation does not allow the collection of race and therefore French subjects are not included in this baseline measure.
Region of Enrollment; Measure Type: Number; Unit of measure: Participants
Netherlands	Number Analyzed	48 participants	51 participants	99 participants
		1	3	4
Belgium	Number Analyzed	48 participants	51 participants	99 participants
		3	2	5
Ireland	Number Analyzed	48 participants	51 participants	99 participants
		2	0	2
Denmark	Number Analyzed	48 participants	51 participants	99 participants
		1	2	3
Poland	Number Analyzed	48 participants	51 participants	99 participants
		12	10	22
Italy	Number Analyzed	48 participants	51 participants	99 participants
		2	6	8
United Kingdom	Number Analyzed	48 participants	51 participants	99 participants
		6	9	15
France	Number Analyzed	48 participants	51 participants	99 participants
		12	13	25
Germany	Number Analyzed	48 participants	51 participants	99 participants
		8	3	11
Spain	Number Analyzed	48 participants	51 participants	99 participants
		1	3	4
Quality of Life (QoL) Questionnaire Core 30 (QLQ-C30) Score [1] [2]; Mean (Standard Deviation); Unit of measure: Score on a scale
	Number Analyzed	46 participants	50 participants	96 participants
		68.12 (19.74)	67.83 (20.76)	67.97 (20.17)
		[1] Measure Description: QoL was measured Using European Organisation Into the Research and Treatment of Cancer (EORTC), QLQ-C30 v3.0. 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.; [2] Measure Analysis Population Description: Only subjects who had a QLQ-C30 measure at baseline are included.
EuroQoL 5 Dimensions, 5 Levels (EQ-5D-5L) v1.0 Questionnaire Descriptive System Score [1] [2]; Mean (Standard Deviation); Unit of measure: Score on a scale
	Number Analyzed	45 participants	45 participants	90 participants
		0.82 (0.17)	0.83 (0.14)	0.83 (0.15)
		[1] Measure Description: 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).; [2] Measure Analysis Population Description: Only subjects with a EQ-5D-5L index value at baseline are included.
EQ-5D-5L Visual Analogue Scale (VAS) Score [1] [2]; Mean (Standard Deviation); Unit of measure: Score on a scale
	Number Analyzed	47 participants	44 participants	91 participants
		75.02 (17.93)	70.45 (14.93)	72.81 (16.62)
		[1] Measure Description: 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).; [2] Measure Analysis Population Description: Only subjects with a EQ-5D-5L VAS score at baseline are included.
QoL Questionnaire Gastrointestinal Neuroendocrine Tumour 21 (QLQ-GI.NET21) Score [1] [2]; Mean (Standard Deviation); Unit of measure: Score on a scale
Endocrine Symptoms	Number Analyzed	45 participants	49 participants	94 participants
		16.54 (22.30)	19.73 (22.82)	18.20 (22.51)
Gastrointestinal Symptoms	Number Analyzed	45 participants	49 participants	94 participants
		21.70 (20.01)	22.04 (17.17)	21.88 (18.48)
Treatment Related Symptoms	Number Analyzed	32 participants	32 participants	64 participants
		11.63 (13.11)	11.46 (13.75)	11.55 (13.33)
Social Function	Number Analyzed	45 participants	49 participants	94 participants
		32.84 (24.18)	35.03 (24.33)	33.98 (24.15)
Disease Related Worries	Number Analyzed	45 participants	49 participants	94 participants
		44.44 (29.96)	44.22 (25.83)	44.33 (27.74)
Muscle/Bone Pain	Number Analyzed	44 participants	48 participants	92 participants
		26.52 (30.99)	25.69 (30.16)	26.09 (30.39)
Sexual Function	Number Analyzed	31 participants	28 participants	59 participants
		22.58 (30.29)	17.86 (27.94)	20.34 (29.04)
Information/Communication Function	Number Analyzed	45 participants	48 participants	93 participants
		3.70 (12.76)	4.17 (11.14)	3.94 (11.89)
Body Image	Number Analyzed	44 participants	45 participants	89 participants
		10.61 (23.60)	15.56 (28.95)	13.11 (26.41)
		[1] Measure Description: The EORTC QLQ-GI.NET21 module 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 single items (sexuality and communication). Answers were converted on a grading scale and then individual sub-scores transformed to range from 0 to 100 with a higher score = more or worse problems.; [2] Measure Analysis Population Description: Only subjects who had a QLQ GI.NET21 measure at baseline are included.
Categories of Proliferation index Ki67; Measure Type: Number; Unit of measure: Participants
≥10%	Number Analyzed	48 participants	51 participants	99 participants
		7	4	11
<10%	Number Analyzed	48 participants	51 participants	99 participants
		41	46	87
Missing	Number Analyzed	48 participants	51 participants	99 participants
		0	1	1
Tumour grading (according to WHO 2010 classification) [1]; Measure Type: Number; Unit of measure: Participants
Grade 1	Number Analyzed	48 participants	51 participants	99 participants
		12	29	41
Grade 2	Number Analyzed	48 participants	51 participants	99 participants
		36	22	58
		[1] Measure Description: According to the 2010 WHO classification, Grade 1 NET is defined as <=2% Ki-67 labelling index; and Grade 2 NET is defined as 3-20% Ki-67 labelling index. Grade 2 is considered to have a worse outcome.
Hepatic tumour load; Measure Type: Number; Unit of measure: Participants
>25%	Number Analyzed	48 participants	51 participants	99 participants
		7	9	16
≤25%	Number Analyzed	48 participants	51 participants	99 participants
		41	42	83

Outcome Measures

1. Primary Outcome

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.
Overall Number of Participants Analyzed	48	51
Median (95% Confidence Interval); Unit of Measure: months
	5.6; (5.5 to 8.3)	8.3; (5.6 to 11.1)

2. Secondary Outcome

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.
Overall Number of Participants Analyzed	48	51
Median (95% Confidence Interval); Unit of Measure: months
	5.6; (5.5 to 8.3)	8.7; (8.3 to 13.9)

3. Secondary Outcome

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.
Overall Number of Participants Analyzed		48	51
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of subjects
Week 12	Number Analyzed	48 participants	51 participants
		93.3; (80.7 to 97.8)	91.8; (79.7 to 96.9)
Week 24	Number Analyzed	48 participants	51 participants
		64.4; (48.7 to 76.5)	65.3; (50.3 to 76.8)
Week 36	Number Analyzed	48 participants	51 participants
		37.8; (23.9 to 51.6)	59.2; (44.2 to 71.4)
Week 48	Number Analyzed	48 participants	51 participants
		28.5; (16.2 to 42.1)	38.3; (24.8 to 51.6)
Week 60	Number Analyzed	48 participants	51 participants
		20.7; (9.0 to 35.7)	36.1; (22.9 to 49.5)
Week 72	Number Analyzed	0 participants	51 participants
			29.8; (17.6 to 42.9)
Week 84	Number Analyzed	0 participants	51 participants
			27.5; (15.7 to 40.5)
Week 96	Number Analyzed	0 participants	51 participants
			25.2; (13.9 to 38.1)

4. Secondary Outcome

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.
Overall Number of Participants Analyzed	48	51
Median (95% Confidence Interval); Unit of Measure: months
	NA [1]; (NA to NA)	NA [1]; (NA to NA)

[1]

The median overall survival from the Kaplan Meier model was not reached for this cohort.

5. Secondary Outcome

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.
Overall Number of Participants Analyzed		48	51
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of subjects
Week 12	Number Analyzed	48 participants	51 participants
		0.0; (0.0 to 7.4)	0.0; (0.0 to 7.0)
Week 24	Number Analyzed	48 participants	51 participants
		0.0; (0.0 to 7.4)	0.0; (0.0 to 7.0)
Week 36	Number Analyzed	48 participants	51 participants
		0.0; (0.0 to 7.4)	0.0; (0.0 to 7.0)
Week 48	Number Analyzed	48 participants	51 participants
		0.0; (0.0 to 7.4)	0.0; (0.0 to 7.0)
Week 60	Number Analyzed	48 participants	51 participants
		0.0; (0.0 to 7.4)	2.0; (0.0 to 10.4)
Week 72	Number Analyzed	0 participants	51 participants
			3.9; (0.5 to 13.5)
Week 84	Number Analyzed	0 participants	51 participants
			2.0; (0.0 to 10.4)
Week 96	Number Analyzed	0 participants	51 participants
			2.0; (0.0 to 10.4)

6. Secondary Outcome

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.
Overall Number of Participants Analyzed	48	51
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of subjects
Week 24	43.8; (29.5 to 58.8)	58.8; (44.2 to 72.4)
Week 48	22.9; (12.0 to 37.3)	33.3; (20.8 to 47.9)

7. Secondary Outcome

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.
Overall Number of Participants Analyzed	48	51
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of subjects
CR	0.0; (0.0 to 7.4)	0.0; (0.0 to 7.0)
PR	0.0; (0.0 to 7.4)	3.9; (0.5 to 13.5)
SD	66.7; (51.6 to 79.6)	68.6; (54.1 to 80.9)
PD	31.3; (18.7 to 46.3)	23.5; (12.8 to 37.5)
Not evaluable	0.0; (0.0 to 7.4)	2.0; (0.0 to 10.4)

8. Secondary Outcome

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.
Overall Number of Participants Analyzed	48	51
Median (95% Confidence Interval); Unit of Measure: months
	8.3; (8.0 to 13.8)	13.8 [1]; (8.6 to NA)

[1]

95% confidence interval upper limit could not be calculated as an insufficient number of events were observed.

9. Secondary Outcome

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.
Overall Number of Participants Analyzed		48	51
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: Hazard Ratio
Hepatic tumour load: >25% Vs ≤25%	Number Analyzed	48 participants	51 participants
		0.96; (0.40 to 2.32)	1.54; (0.70 to 3.40)
Tumour Grade: 2 Vs 1	Number Analyzed	48 participants	51 participants
		0.68; (0.32 to 1.45)	0.90; (0.46 to 1.77)
Previous surgery: No Vs Yes	Number Analyzed	48 participants	51 participants
		1.04; (0.53 to 2.04)	2.14; (0.83 to 5.52)
Ki67: ≥10% Vs <10%	Number Analyzed	48 participants	50 participants
		3.60; (1.39 to 9.32)	2.26; (0.67 to 7.60)
Duration of treatment with lanreotide Autogel® 120 mg every 28 days: ≥median Vs <median	Number Analyzed	48 participants	51 participants
		0.68; (0.34 to 1.34)	0.76; (0.40 to 1.47)
Age: ≥65 years Vs <65 years	Number Analyzed	48 participants	51 participants
		1.55; (0.79 to 3.06)	1.15; (0.58 to 2.31)
Time from diagnosis: ≥3 years Vs <3 years	Number Analyzed	48 participants	51 participants
		0.49; (0.25 to 0.96)	0.94; (0.49 to 1.82)
Time between CT scans: ≥12 months Vs <12 months	Number Analyzed	48 participants	51 participants
		0.47; (0.24 to 0.94)	0.72; (0.37 to 1.39)
Symptoms: No Vs Yes	Number Analyzed	48 participants	50 participants
		2.55; (0.89 to 7.28)	1.32; (0.68 to 2.56)

10. Secondary Outcome

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.
Overall Number of Participants Analyzed		48	51
Mean (Standard Deviation); Unit of Measure: episodes
Stools - Week 8	Number Analyzed	5 participants	13 participants
		1.0 (5.5)	-1.0 (8.2)
Stools - Week 12	Number Analyzed	5 participants	13 participants
		-1.2 (7.9)	0.7 (2.5)
Stools - Week 48	Number Analyzed	2 participants	5 participants
		-1.0 (0.0)	3.4 (4.8)
Stools - End of Study	Number Analyzed	4 participants	5 participants
		0.5 (5.4)	-1.2 (12.2)
Flushing - Week 8	Number Analyzed	3 participants	9 participants
		0.7 (2.1)	-3.3 (8.3)
Flushing - Week 12	Number Analyzed	2 participants	6 participants
		-1.0 (0.0)	1.5 (10.0)
Flushing - Week 48	Number Analyzed	2 participants	2 participants
		-1.0 (0.0)	-1.5 (2.1)
Flushing - End of Study	Number Analyzed	2 participants	4 participants
		0.0 (1.4)	-0.5 (6.2)

11. Secondary Outcome

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.
Overall Number of Participants Analyzed	22	25	47
Mean (Standard Deviation); Unit of Measure: score on a scale
	-0.38 (15.32)	-1.33 (17.13)	-0.89 (16.14)

12. Secondary Outcome

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.
Overall Number of Participants Analyzed	22	21	43
Mean (Standard Deviation); Unit of Measure: Index value
	-0.04 (0.12)	0.00 (0.11)	-0.02 (0.12)

13. Secondary Outcome

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.
Overall Number of Participants Analyzed	21	21	42
Mean (Standard Deviation); Unit of Measure: score on a scale
	-1.90 (14.80)	-1.76 (9.34)	-1.83 (12.22)

14. Secondary Outcome

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.
Overall Number of Participants Analyzed		48	51	99
Mean (Standard Deviation); Unit of Measure: score on a scale
Endocrine Symptoms	Number Analyzed	21 participants	24 participants	45 participants
		-0.53 (11.37)	-5.09 (17.33)	-2.96 (14.87)
Gastrointestinal Symptoms	Number Analyzed	21 participants	24 participants	45 participants
		-3.49 (14.24)	-2.78 (15.96)	-3.11 (15.02)
Treatment Related Symptoms	Number Analyzed	15 participants	16 participants	31 participants
		5.93 (15.64)	-3.47 (14.47)	1.08 (15.54)
Social Function	Number Analyzed	21 participants	24 participants	45 participants
		-0.79 (13.41)	-9.49 (18.20)	-5.43 (16.56)
Disease Related Worries	Number Analyzed	21 participants	24 participants	45 participants
		3.17 (15.47)	-0.93 (27.40)	0.99 (22.48)
Muscle/Bone Pain	Number Analyzed	20 participants	24 participants	44 participants
		-1.67 (33.29)	0.00 (36.78)	-0.76 (34.84)
Sexual Function	Number Analyzed	14 participants	12 participants	26 participants
		2.38 (15.82)	-2.78 (26.43)	0.00 (21.08)
Information/Communication Function	Number Analyzed	21 participants	23 participants	44 participants
		7.94 (29.64)	-2.90 (9.60)	2.27 (22.04)
Body Image	Number Analyzed	20 participants	22 participants	42 participants
		0.00 (15.29)	-7.58 (28.97)	-3.97 (23.52)

15. Secondary Outcome

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.
Overall Number of Participants Analyzed		48	51
Mean (Standard Deviation); Unit of Measure: xULN
CgA	Number Analyzed	22 participants	24 participants
		0.205 (1.258)	0.370 (1.843)
NSE	Number Analyzed	15 participants	10 participants
		0.03 (1.00)	-0.49 (1.86)
Plasma 5-HIAA	Number Analyzed	20 participants	17 participants
		-0.42 (1.44)	3.90 (7.39)

16. Secondary Outcome

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.
Overall Number of Participants Analyzed		48
Mean (Standard Deviation); Unit of Measure: pmol/L
Pancreatic Polypeptide	Number Analyzed	3 participants
		82.7 (146.7)
Gastrin	Number Analyzed	4 participants
		-9.8 (70.7)

17. Secondary Outcome

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.
Overall Number of Participants Analyzed	4
Mean (Standard Deviation); Unit of Measure: 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 (%)		Affected / at Risk (%)		Affected / at Risk (%)
Total	1/48 (2.08%)		3/51 (5.88%)		4/99 (4.04%)
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 (10.42%)		13/51 (25.49%)		18/99 (18.18%)
Cardiac disorders
Cardiac failure † 1	0/48 (0.00%)	0	1/51 (1.96%)	1	1/99 (1.01%)	1
Pulseless electrical activity † 1	0/48 (0.00%)	0	1/51 (1.96%)	1	1/99 (1.01%)	1
Gastrointestinal disorders
Abdominal pain † 1	0/48 (0.00%)	0	1/51 (1.96%)	2	1/99 (1.01%)	2
Diarrhoea † 1	1/48 (2.08%)	1	0/51 (0.00%)	0	1/99 (1.01%)	1
Intestinal obstruction † 1	0/48 (0.00%)	0	1/51 (1.96%)	1	1/99 (1.01%)	1
General disorders
Asthenia † 1	0/48 (0.00%)	0	1/51 (1.96%)	1	1/99 (1.01%)	1
Chest pain † 1	0/48 (0.00%)	0	1/51 (1.96%)	1	1/99 (1.01%)	1
General physical health deterioration † 1	0/48 (0.00%)	0	1/51 (1.96%)	1	1/99 (1.01%)	1
Immune system disorders
Anaphylactic reaction † 1	1/48 (2.08%)	1	0/51 (0.00%)	0	1/99 (1.01%)	1
Infections and infestations
Peritonitis † 1	0/48 (0.00%)	0	1/51 (1.96%)	1	1/99 (1.01%)	1
Viral infection † 1	0/48 (0.00%)	0	1/51 (1.96%)	1	1/99 (1.01%)	1
Injury, poisoning and procedural complications
Craniocerebral injury † 1	0/48 (0.00%)	0	1/51 (1.96%)	1	1/99 (1.01%)	1
Fall † 1	1/48 (2.08%)	1	0/51 (0.00%)	0	1/99 (1.01%)	1
Spinal fracture † 1	1/48 (2.08%)	1	0/51 (0.00%)	0	1/99 (1.01%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Bone neoplasm † 1	0/48 (0.00%)	0	1/51 (1.96%)	1	1/99 (1.01%)	1
Breast cancer † 1	0/48 (0.00%)	0	1/51 (1.96%)	1	1/99 (1.01%)	1
Nervous system disorders
Spinal cord compression † 1	0/48 (0.00%)	0	1/51 (1.96%)	1	1/99 (1.01%)	1
Syncope † 1	1/48 (2.08%)	1	0/51 (0.00%)	0	1/99 (1.01%)	1
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism † 1	1/48 (2.08%)	1	2/51 (3.92%)	3	3/99 (3.03%)	4
Vascular disorders
Hypotension † 1	0/48 (0.00%)	0	1/51 (1.96%)	1	1/99 (1.01%)	1
1 Term from vocabulary, MedDRA 22.0; † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0%
	PanNET Cohort		Midgut NET Cohort		Overall Subjects
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	41/48 (85.42%)		47/51 (92.16%)		88/99 (88.89%)
Blood and lymphatic system disorders
Lymphopenia † 1	1/48 (2.08%)	1	0/51 (0.00%)	0	1/99 (1.01%)	1
Monocytopenia † 1	1/48 (2.08%)	1	0/51 (0.00%)	0	1/99 (1.01%)	1
Cardiac disorders
Arrhythmia † 1	1/48 (2.08%)	1	0/51 (0.00%)	0	1/99 (1.01%)	1
Cardiac failure † 1	0/48 (0.00%)	0	1/51 (1.96%)	2	1/99 (1.01%)	2
Heart valve incompetence † 1	0/48 (0.00%)	0	1/51 (1.96%)	1	1/99 (1.01%)	1
Palpitations † 1	1/48 (2.08%)	1	0/51 (0.00%)	0	1/99 (1.01%)	1
Right ventricular failure † 1	0/48 (0.00%)	0	1/51 (1.96%)	1	1/99 (1.01%)	1
Tachycardia † 1	1/48 (2.08%)	1	0/51 (0.00%)	0	1/99 (1.01%)	1
Tricuspid valve disease † 1	0/48 (0.00%)	0	1/51 (1.96%)	1	1/99 (1.01%)	1
Ear and labyrinth disorders
Deafness † 1	1/48 (2.08%)	1	0/51 (0.00%)	0	1/99 (1.01%)	1
Deafness unilateral † 1	1/48 (2.08%)	1	0/51 (0.00%)	0	1/99 (1.01%)	1
Ear pain † 1	0/48 (0.00%)	0	1/51 (1.96%)	1	1/99 (1.01%)	1
Hypoacusis † 1	1/48 (2.08%)	1	0/51 (0.00%)	0	1/99 (1.01%)	1
Vertigo † 1	0/48 (0.00%)	0	1/51 (1.96%)	2	1/99 (1.01%)	2
Vertigo positional † 1	1/48 (2.08%)	1	0/51 (0.00%)	0	1/99 (1.01%)	1
Eye disorders
Diplopia † 1	0/48 (0.00%)	0	1/51 (1.96%)	1	1/99 (1.01%)	1
Dry eye † 1	0/48 (0.00%)	0	1/51 (1.96%)	1	1/99 (1.01%)	1
Eye pain † 1	0/48 (0.00%)	0	1/51 (1.96%)	1	1/99 (1.01%)	1
Eye pruritus † 1	0/48 (0.00%)	0	1/51 (1.96%)	1	1/99 (1.01%)	1
Glaucoma † 1	0/48 (0.00%)	0	1/51 (1.96%)	1	1/99 (1.01%)	1
Ocular hyperaemia † 1	0/48 (0.00%)	0	2/51 (3.92%)	2	2/99 (2.02%)	2
Gastrointestinal disorders
Abdominal discomfort † 1	0/48 (0.00%)	0	1/51 (1.96%)	1	1/99 (1.01%)	1
Abdominal distension † 1	0/48 (0.00%)	0	6/51 (11.76%)	7	6/99 (6.06%)	7
Abdominal pain † 1	7/48 (14.58%)	13	12/51 (23.53%)	16	19/99 (19.19%)	29
Abdominal pain lower † 1	1/48 (2.08%)	1	1/51 (1.96%)	1	2/99 (2.02%)	2
Abdominal pain upper † 1	2/48 (4.17%)	2	6/51 (11.76%)	7	8/99 (8.08%)	9
Anal incontinence † 1	1/48 (2.08%)	1	0/51 (0.00%)	0	1/99 (1.01%)	1
Anorectal discomfort † 1	0/48 (0.00%)	0	1/51 (1.96%)	1	1/99 (1.01%)	1
Ascites † 1	0/48 (0.00%)	0	2/51 (3.92%)	2	2/99 (2.02%)	2
Constipation † 1	2/48 (4.17%)	3	2/51 (3.92%)	3	4/99 (4.04%)	6
Diarrhoea † 1	14/48 (29.17%)	20	27/51 (52.94%)	35	41/99 (41.41%)	55
Dry mouth † 1	1/48 (2.08%)	1	0/51 (0.00%)	0	1/99 (1.01%)	1
Dyspepsia † 1	0/48 (0.00%)	0	2/51 (3.92%)	3	2/99 (2.02%)	3
Faeces discoloured † 1	0/48 (0.00%)	0	1/51 (1.96%)	1	1/99 (1.01%)	1
Flatulence † 1	1/48 (2.08%)	1	6/51 (11.76%)	8	7/99 (7.07%)	9
Gastrooesophageal reflux disease † 1	1/48 (2.08%)	1	2/51 (3.92%)	2	3/99 (3.03%)	3
Gingival bleeding † 1	1/48 (2.08%)	1	0/51 (0.00%)	0	1/99 (1.01%)	1
Gingival pain † 1	1/48 (2.08%)	1	1/51 (1.96%)	1	2/99 (2.02%)	2
Glossodynia † 1	0/48 (0.00%)	0	1/51 (1.96%)	1	1/99 (1.01%)	1
Haematochezia † 1	1/48 (2.08%)	1	0/51 (0.00%)	0	1/99 (1.01%)	1
Hernial eventration † 1	0/48 (0.00%)	0	1/51 (1.96%)	1	1/99 (1.01%)	1
Inguinal hernia † 1	0/48 (0.00%)	0	1/51 (1.96%)	1	1/99 (1.01%)	1
Nausea † 1	5/48 (10.42%)	5	6/51 (11.76%)	9	11/99 (11.11%)	14
Oral pain † 1	0/48 (0.00%)	0	1/51 (1.96%)	1	1/99 (1.01%)	1
Pancreatic failure † 1	0/48 (0.00%)	0	1/51 (1.96%)	1	1/99 (1.01%)	1
Proctalgia † 1	0/48 (0.00%)	0	1/51 (1.96%)	1	1/99 (1.01%)	1
Steatorrhoea † 1	2/48 (4.17%)	2	3/51 (5.88%)	3	5/99 (5.05%)	5
Stomatitis † 1	1/48 (2.08%)	1	1/51 (1.96%)	1	2/99 (2.02%)	2
Toothache † 1	1/48 (2.08%)	1	0/51 (0.00%)	0	1/99 (1.01%)	1
Vomiting † 1	6/48 (12.50%)	9	4/51 (7.84%)	4	10/99 (10.10%)	13
Haemorrhoids † 1	1/48 (2.08%)	1	1/51 (1.96%)	1	2/99 (2.02%)	2
General disorders
Asthenia † 1	4/48 (8.33%)	24	4/51 (7.84%)	5	8/99 (8.08%)	29
Chest pain † 1	0/48 (0.00%)	0	3/51 (5.88%)	3	3/99 (3.03%)	3
Fatigue † 1	7/48 (14.58%)	8	8/51 (15.69%)	11	15/99 (15.15%)	19
Gait disturbance † 1	0/48 (0.00%)	0	1/51 (1.96%)	1	1/99 (1.01%)	1
Hunger † 1	0/48 (0.00%)	0	1/51 (1.96%)	1	1/99 (1.01%)	1
Influenza like illness † 1	1/48 (2.08%)	1	3/51 (5.88%)	3	4/99 (4.04%)	4
Injection site bruising † 1	1/48 (2.08%)	1	0/51 (0.00%)	0	1/99 (1.01%)	1
Injection site pain † 1	0/48 (0.00%)	0	1/51 (1.96%)	1	1/99 (1.01%)	1
Malaise † 1	1/48 (2.08%)	1	2/51 (3.92%)	2	3/99 (3.03%)	3
Medical device site pain † 1	1/48 (2.08%)	1	0/51 (0.00%)	0	1/99 (1.01%)	1
Oedema peripheral † 1	2/48 (4.17%)	2	2/51 (3.92%)	2	4/99 (4.04%)	4
Pain † 1	0/48 (0.00%)	0	1/51 (1.96%)	1	1/99 (1.01%)	1
Peripheral swelling † 1	0/48 (0.00%)	0	3/51 (5.88%)	3	3/99 (3.03%)	3
Polyp † 1	0/48 (0.00%)	0	1/51 (1.96%)	1	1/99 (1.01%)	1
Pyrexia † 1	2/48 (4.17%)	2	2/51 (3.92%)	5	4/99 (4.04%)	7
Hepatobiliary disorders
Bile duct stone † 1	0/48 (0.00%)	0	1/51 (1.96%)	1	1/99 (1.01%)	1
Cholelithiasis † 1	0/48 (0.00%)	0	3/51 (5.88%)	3	3/99 (3.03%)	3
Hepatic failure † 1	0/48 (0.00%)	0	1/51 (1.96%)	1	1/99 (1.01%)	1
Liver injury † 1	1/48 (2.08%)	1	0/51 (0.00%)	0	1/99 (1.01%)	1
Immune system disorders
Drug hypersensitivity † 1	0/48 (0.00%)	0	1/51 (1.96%)	1	1/99 (1.01%)	1
Infections and infestations
Bronchitis † 1	0/48 (0.00%)	0	1/51 (1.96%)	1	1/99 (1.01%)	1
Carbuncle † 1	0/48 (0.00%)	0	1/51 (1.96%)	1	1/99 (1.01%)	1
Cystitis † 1	2/48 (4.17%)	2	1/51 (1.96%)	1	3/99 (3.03%)	3
Cystitis bacterial † 1	0/48 (0.00%)	0	1/51 (1.96%)	1	1/99 (1.01%)	1
Diverticulitis † 1	0/48 (0.00%)	0	2/51 (3.92%)	2	2/99 (2.02%)	2
Folliculitis † 1	0/48 (0.00%)	0	1/51 (1.96%)	1	1/99 (1.01%)	1
Herpes zoster † 1	0/48 (0.00%)	0	2/51 (3.92%)	2	2/99 (2.02%)	2
Influenza † 1	2/48 (4.17%)	2	3/51 (5.88%)	6	5/99 (5.05%)	8
Lower respiratory tract infection † 1	1/48 (2.08%)	2	3/51 (5.88%)	3	4/99 (4.04%)	5
Nasopharyngitis † 1	7/48 (14.58%)	7	5/51 (9.80%)	6	12/99 (12.12%)	13
Respiratory tract infection † 1	0/48 (0.00%)	0	1/51 (1.96%)	1	1/99 (1.01%)	1
Tonsillitis † 1	1/48 (2.08%)	1	0/51 (0.00%)	0	1/99 (1.01%)	1
Upper respiratory tract infection † 1	0/48 (0.00%)	0	1/51 (1.96%)	1	1/99 (1.01%)	1
Urinary tract infection † 1	4/48 (8.33%)	6	1/51 (1.96%)	1	5/99 (5.05%)	7
Injury, poisoning and procedural complications
Fall † 1	0/48 (0.00%)	0	1/51 (1.96%)	1	1/99 (1.01%)	1
Incision site pain † 1	0/48 (0.00%)	0	1/51 (1.96%)	1	1/99 (1.01%)	1
Incisional hernia † 1	0/48 (0.00%)	0	1/51 (1.96%)	1	1/99 (1.01%)	1
Ligament sprain † 1	0/48 (0.00%)	0	2/51 (3.92%)	2	2/99 (2.02%)	2
Muscle strain † 1	0/48 (0.00%)	0	1/51 (1.96%)	1	1/99 (1.01%)	1
Post procedural complication † 1	1/48 (2.08%)	1	0/51 (0.00%)	0	1/99 (1.01%)	1
Radiation skin injury † 1	0/48 (0.00%)	0	1/51 (1.96%)	1	1/99 (1.01%)	1
Skin abrasion † 1	1/48 (2.08%)	1	0/51 (0.00%)	0	1/99 (1.01%)	1
Investigations
Alanine aminotransferase increased † 1	1/48 (2.08%)	1	2/51 (3.92%)	2	3/99 (3.03%)	3
Aspartate aminotransferase abnormal † 1	1/48 (2.08%)	1	0/51 (0.00%)	0	1/99 (1.01%)	1
Aspartate aminotransferase increased † 1	1/48 (2.08%)	1	1/51 (1.96%)	1	2/99 (2.02%)	2
Bacterial test positive † 1	0/48 (0.00%)	0	1/51 (1.96%)	1	1/99 (1.01%)	1
Blood alkaline phosphatase increased † 1	3/48 (6.25%)	3	1/51 (1.96%)	1	4/99 (4.04%)	4
Blood bilirubin increased † 1	0/48 (0.00%)	0	2/51 (3.92%)	2	2/99 (2.02%)	2
Blood chromogranin A increased † 1	0/48 (0.00%)	0	1/51 (1.96%)	1	1/99 (1.01%)	1
Blood creatinine increased † 1	1/48 (2.08%)	1	0/51 (0.00%)	0	1/99 (1.01%)	1
Blood glucose decreased † 1	0/48 (0.00%)	0	1/51 (1.96%)	1	1/99 (1.01%)	1
Blood glucose increased † 1	1/48 (2.08%)	1	1/51 (1.96%)	1	2/99 (2.02%)	2
Blood potassium increased † 1	1/48 (2.08%)	1	0/51 (0.00%)	0	1/99 (1.01%)	1
Blood triglycerides increased † 1	0/48 (0.00%)	0	1/51 (1.96%)	1	1/99 (1.01%)	1
Blood urea increased † 1	1/48 (2.08%)	1	1/51 (1.96%)	1	2/99 (2.02%)	2
Blood urine present † 1	0/48 (0.00%)	0	1/51 (1.96%)	1	1/99 (1.01%)	1
C-reactive protein increased † 1	0/48 (0.00%)	0	1/51 (1.96%)	1	1/99 (1.01%)	1
Gamma-glutamyltransferase abnormal † 1	1/48 (2.08%)	1	0/51 (0.00%)	0	1/99 (1.01%)	1
Gamma-glutamyltransferase decreased † 1	0/48 (0.00%)	0	1/51 (1.96%)	1	1/99 (1.01%)	1
Gamma-glutamyltransferase increased † 1	1/48 (2.08%)	1	2/51 (3.92%)	2	3/99 (3.03%)	3
Glycosylated haemoglobin increased † 1	1/48 (2.08%)	1	0/51 (0.00%)	0	1/99 (1.01%)	1
Lymphocyte count decreased † 1	0/48 (0.00%)	0	1/51 (1.96%)	1	1/99 (1.01%)	1
Neutrophil count decreased † 1	0/48 (0.00%)	0	1/51 (1.96%)	1	1/99 (1.01%)	1
Platelet count decreased † 1	0/48 (0.00%)	0	1/51 (1.96%)	1	1/99 (1.01%)	1
Specific gravity urine increased † 1	1/48 (2.08%)	1	0/51 (0.00%)	0	1/99 (1.01%)	1
Urine ketone body present † 1	2/48 (4.17%)	2	0/51 (0.00%)	0	2/99 (2.02%)	2
Weight decreased † 1	1/48 (2.08%)	1	2/51 (3.92%)	2	3/99 (3.03%)	3
Metabolism and nutrition disorders
Carbohydrate intolerance † 1	1/48 (2.08%)	1	0/51 (0.00%)	0	1/99 (1.01%)	1
Decreased appetite † 1	5/48 (10.42%)	5	2/51 (3.92%)	2	7/99 (7.07%)	7
Hypercholesterolaemia † 1	0/48 (0.00%)	0	1/51 (1.96%)	1	1/99 (1.01%)	1
Hyperglycaemia † 1	1/48 (2.08%)	1	1/51 (1.96%)	1	2/99 (2.02%)	2
Hyperkalaemia † 1	0/48 (0.00%)	0	2/51 (3.92%)	2	2/99 (2.02%)	2
Hypernatraemia † 1	0/48 (0.00%)	0	1/51 (1.96%)	1	1/99 (1.01%)	1
Hypertriglyceridaemia † 1	0/48 (0.00%)	0	1/51 (1.96%)	1	1/99 (1.01%)	1
Hyperuricaemia † 1	1/48 (2.08%)	1	0/51 (0.00%)	0	1/99 (1.01%)	1
Hypoalbuminaemia † 1	1/48 (2.08%)	1	0/51 (0.00%)	0	1/99 (1.01%)	1
Hypocalcaemia † 1	1/48 (2.08%)	1	2/51 (3.92%)	2	3/99 (3.03%)	3
Hypoglycaemia † 1	1/48 (2.08%)	3	1/51 (1.96%)	1	2/99 (2.02%)	4
Hypokalaemia † 1	0/48 (0.00%)	0	1/51 (1.96%)	1	1/99 (1.01%)	1
Hyponatraemia † 1	1/48 (2.08%)	1	0/51 (0.00%)	0	1/99 (1.01%)	1
Malnutrition † 1	0/48 (0.00%)	0	1/51 (1.96%)	1	1/99 (1.01%)	1
Vitamin D deficiency † 1	1/48 (2.08%)	1	1/51 (1.96%)	1	2/99 (2.02%)	2
Musculoskeletal and connective tissue disorders
Arthralgia † 1	0/48 (0.00%)	0	5/51 (9.80%)	7	5/99 (5.05%)	7
Back pain † 1	2/48 (4.17%)	2	2/51 (3.92%)	2	4/99 (4.04%)	4
Exostosis † 1	1/48 (2.08%)	1	0/51 (0.00%)	0	1/99 (1.01%)	1
Flank pain † 1	0/48 (0.00%)	0	1/51 (1.96%)	1	1/99 (1.01%)	1
Intervertebral disc degeneration † 1	0/48 (0.00%)	0	1/51 (1.96%)	1	1/99 (1.01%)	1
Intervertebral disc protrusion † 1	0/48 (0.00%)	0	1/51 (1.96%)	1	1/99 (1.01%)	1
Joint swelling † 1	0/48 (0.00%)	0	3/51 (5.88%)	5	3/99 (3.03%)	5
Mobility decreased † 1	1/48 (2.08%)	1	0/51 (0.00%)	0	1/99 (1.01%)	1
Muscle spasms † 1	1/48 (2.08%)	1	2/51 (3.92%)	3	3/99 (3.03%)	4
Musculoskeletal chest pain † 1	1/48 (2.08%)	1	1/51 (1.96%)	1	2/99 (2.02%)	2
Musculoskeletal discomfort † 1	0/48 (0.00%)	0	1/51 (1.96%)	1	1/99 (1.01%)	1
Musculoskeletal pain † 1	1/48 (2.08%)	1	2/51 (3.92%)	2	3/99 (3.03%)	3
Myalgia † 1	0/48 (0.00%)	0	1/51 (1.96%)	2	1/99 (1.01%)	2
Neck pain † 1	0/48 (0.00%)	0	2/51 (3.92%)	2	2/99 (2.02%)	2
Osteoarthritis † 1	1/48 (2.08%)	1	1/51 (1.96%)	1	2/99 (2.02%)	2
Osteoporosis † 1	0/48 (0.00%)	0	1/51 (1.96%)	1	1/99 (1.01%)	1
Pain in extremity † 1	2/48 (4.17%)	2	1/51 (1.96%)	2	3/99 (3.03%)	4
Periarthritis † 1	0/48 (0.00%)	0	1/51 (1.96%)	1	1/99 (1.01%)	1
Rheumatoid arthritis † 1	0/48 (0.00%)	0	1/51 (1.96%)	2	1/99 (1.01%)	2
Spinal pain † 1	1/48 (2.08%)	1	2/51 (3.92%)	2	3/99 (3.03%)	3
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastases to liver † 1	0/48 (0.00%)	0	1/51 (1.96%)	1	1/99 (1.01%)	1
Nervous system disorders
Ageusia † 1	1/48 (2.08%)	1	0/51 (0.00%)	0	1/99 (1.01%)	1
Aphasia † 1	0/48 (0.00%)	0	1/51 (1.96%)	2	1/99 (1.01%)	2
Balance disorder † 1	0/48 (0.00%)	0	1/51 (1.96%)	1	1/99 (1.01%)	1
Dizziness † 1	3/48 (6.25%)	3	5/51 (9.80%)	7	8/99 (8.08%)	10
Dizziness postural † 1	0/48 (0.00%)	0	1/51 (1.96%)	1	1/99 (1.01%)	1
Head discomfort † 1	0/48 (0.00%)	0	1/51 (1.96%)	1	1/99 (1.01%)	1
Headache † 1	3/48 (6.25%)	3	4/51 (7.84%)	5	7/99 (7.07%)	8
Lethargy † 1	1/48 (2.08%)	1	1/51 (1.96%)	1	2/99 (2.02%)	2
Poor quality sleep † 1	1/48 (2.08%)	1	1/51 (1.96%)	1	2/99 (2.02%)	2
Presyncope † 1	0/48 (0.00%)	0	2/51 (3.92%)	2	2/99 (2.02%)	2
Sciatica † 1	0/48 (0.00%)	0	2/51 (3.92%)	2	2/99 (2.02%)	2
Syncope † 1	1/48 (2.08%)	1	0/51 (0.00%)	0	1/99 (1.01%)	1
Taste disorder † 1	1/48 (2.08%)	1	0/51 (0.00%)	0	1/99 (1.01%)	1
Tremor † 1	1/48 (2.08%)	1	2/51 (3.92%)	2	3/99 (3.03%)	3
Psychiatric disorders
Acrophobia † 1	0/48 (0.00%)	0	1/51 (1.96%)	1	1/99 (1.01%)	1
Confusional state † 1	0/48 (0.00%)	0	1/51 (1.96%)	1	1/99 (1.01%)	1
Insomnia † 1	2/48 (4.17%)	2	0/51 (0.00%)	0	2/99 (2.02%)	2
Mood altered † 1	1/48 (2.08%)	1	0/51 (0.00%)	0	1/99 (1.01%)	1
Panic attack † 1	0/48 (0.00%)	0	1/51 (1.96%)	1	1/99 (1.01%)	1
Sleep disorder † 1	0/48 (0.00%)	0	2/51 (3.92%)	2	2/99 (2.02%)	2
Renal and urinary disorders
Chronic kidney disease † 1	0/48 (0.00%)	0	1/51 (1.96%)	1	1/99 (1.01%)	1
Dysuria † 1	0/48 (0.00%)	0	2/51 (3.92%)	2	2/99 (2.02%)	2
Haematuria † 1	1/48 (2.08%)	1	2/51 (3.92%)	2	3/99 (3.03%)	3
Urethral stenosis † 1	0/48 (0.00%)	0	1/51 (1.96%)	1	1/99 (1.01%)	1
Reproductive system and breast disorders
Gynaecomastia † 1	0/48 (0.00%)	0	1/51 (1.96%)	1	1/99 (1.01%)	1
Respiratory, thoracic and mediastinal disorders
Asthma † 1	1/48 (2.08%)	1	0/51 (0.00%)	0	1/99 (1.01%)	1
Cough † 1	3/48 (6.25%)	3	3/51 (5.88%)	3	6/99 (6.06%)	6
Dysphonia † 1	1/48 (2.08%)	1	0/51 (0.00%)	0	1/99 (1.01%)	1
Dyspnoea † 1	0/48 (0.00%)	0	4/51 (7.84%)	5	4/99 (4.04%)	5
Dyspnoea exertional † 1	1/48 (2.08%)	1	2/51 (3.92%)	2	3/99 (3.03%)	3
Increased upper airway secretion † 1	0/48 (0.00%)	0	1/51 (1.96%)	1	1/99 (1.01%)	1
Oropharyngeal pain † 1	0/48 (0.00%)	0	2/51 (3.92%)	2	2/99 (2.02%)	2
Orthopnoea † 1	0/48 (0.00%)	0	1/51 (1.96%)	1	1/99 (1.01%)	1
Productive cough † 1	0/48 (0.00%)	0	1/51 (1.96%)	1	1/99 (1.01%)	1
Sputum discoloured † 1	0/48 (0.00%)	0	1/51 (1.96%)	1	1/99 (1.01%)	1
Skin and subcutaneous tissue disorders
Erythema † 1	0/48 (0.00%)	0	2/51 (3.92%)	2	2/99 (2.02%)	2
Hyperhidrosis † 1	1/48 (2.08%)	1	0/51 (0.00%)	0	1/99 (1.01%)	1
Night sweats † 1	0/48 (0.00%)	0	1/51 (1.96%)	1	1/99 (1.01%)	1
Photosensitivity reaction † 1	1/48 (2.08%)	1	0/51 (0.00%)	0	1/99 (1.01%)	1
Pruritus † 1	1/48 (2.08%)	1	3/51 (5.88%)	4	4/99 (4.04%)	5
Pruritus generalised † 1	0/48 (0.00%)	0	1/51 (1.96%)	1	1/99 (1.01%)	1
Rash † 1	1/48 (2.08%)	1	1/51 (1.96%)	1	2/99 (2.02%)	2
Skin fissures † 1	0/48 (0.00%)	0	1/51 (1.96%)	1	1/99 (1.01%)	1
Skin irritation † 1	0/48 (0.00%)	0	2/51 (3.92%)	2	2/99 (2.02%)	2
Urticaria † 1	0/48 (0.00%)	0	1/51 (1.96%)	1	1/99 (1.01%)	1
Surgical and medical procedures
Injection † 1	0/48 (0.00%)	0	1/51 (1.96%)	1	1/99 (1.01%)	1
Vascular disorders
Deep vein thrombosis † 1	0/48 (0.00%)	0	1/51 (1.96%)	1	1/99 (1.01%)	1
Flushing † 1	2/48 (4.17%)	2	9/51 (17.65%)	14	11/99 (11.11%)	16
Haematoma † 1	0/48 (0.00%)	0	1/51 (1.96%)	1	1/99 (1.01%)	1
Hot flush † 1	0/48 (0.00%)	0	2/51 (3.92%)	14	2/99 (2.02%)	14
Hypertension † 1	2/48 (4.17%)	2	9/51 (17.65%)	9	11/99 (11.11%)	11
Peripheral venous disease † 1	0/48 (0.00%)	0	1/51 (1.96%)	1	1/99 (1.01%)	1
Venous thrombosis limb † 1	1/48 (2.08%)	1	0/51 (0.00%)	0	1/99 (1.01%)	1
1 Term from vocabulary, MedDRA 22.0; † Indicates events were collected by systematic assessment

Limitations and 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
• EMail: clinical.trials@ipsen.com

• Responsible Party: Ipsen
• ClinicalTrials.gov Identifier: NCT02651987
• Other Study ID Numbers: 8-79-52030-326; 2014-005607-24 ( EudraCT Number )
• First Submitted: December 11, 2015
• First Posted: January 11, 2016
• Results First Submitted: October 16, 2020
• Results First Posted: December 30, 2020
• Last Update Posted: December 30, 2020