Somatuline Autogel Preference and Health Economy Study (SAPHE)

• ClinicalTrials.gov Identifier: NCT00681187
• Recruitment Status: Completed
• First Posted: May 21, 2008
• Results First Posted: March 13, 2012
• Last Update Posted: November 22, 2019
• Sponsor: Ipsen
• Information provided by (Responsible Party): Ipsen

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Crossover Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Neuroendocrine Tumour With Carcinoid Symptoms
• Intervention: Drug: lanreotide (Autogel formulation)
• Enrollment: 26

Participant Flow

Recruitment Details	Data from ninety-four subjects was reviewed in hospital clinics in Denmark, Norway and Sweden. Of which 32 were ineligible, 36 were eligible but chose not to participate due to lack of motivation, satisfaction with current form of administration or fear of self-injection and 26 were included. Patients were recruited from Jun-08 to Jan-10.
Pre-assignment Details

Arm/Group Title	Group 1 Self or Partner First Then HCP Administration	Group 2 HCP Then Self or Partner Administration
Arm/Group Description	Started with a training period where the subject or partner performed two or three training injections under supervision of a Healthcare Professional (HCP) at a healthcare provider facility. The training injections were followed by a self administration block of three subsequent unsupervised injections every 28th day at the subject's home. A healthcare administration block followed the self administration block with three HCP provided injections according to clinical routine every 28th day.	Started with a healthcare administration block with three HCP provided injections according to clinical routine every 28th day. A training period followed the healthcare administration block with two or three training injections performed by the subject or partner under supervision at the healthcare provider facilities. A self-administration block followed the training injections with 3 subsequent unsupervised injections every 28th day at the subject's home. The subject visited the clinic for a follow-up visit 14 days after the last self-partner administered injection.
Period Title: Overall Study
Started	11	15
Completed	10	13
Not Completed	1	2
Reason Not Completed
Withdrawal by Subject	1	0
Death	0	1
Adverse Event	0	1

Baseline Characteristics

Arm/Group Title		Group 1 Self or Partner First Then HCP Administration	Group 2 HCP Then Self or Partner Administration	Total
Arm/Group Description		Self or partner administration followed by HCP administration.	Administration by HCP then self or partner administration.	Total of all reporting groups
Overall Number of Baseline Participants		11	15	26
Baseline Analysis Population Description		[Not Specified]
Age, Categorical; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	11 participants	15 participants	26 participants
	<=18 years	0 0.0%	0 0.0%	0 0.0%
	Between 18 and 65 years	6 54.5%	8 53.3%	14 53.8%
	>=65 years	5 45.5%	7 46.7%	12 46.2%
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	11 participants	15 participants	26 participants
		63.2 (6.5)	60.0 (12.7)	61.4 (10.5)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	11 participants	15 participants	26 participants
	Female	4 36.4%	8 53.3%	12 46.2%
	Male	7 63.6%	7 46.7%	14 53.8%
Region of Enrollment; Measure Type: Number; Unit of measure: Participants	Number Analyzed	11 participants	15 participants	26 participants
Denmark		3	4	7
Norway		1	3	4
Sweden		7	8	15

Outcome Measures

1. Primary Outcome

Title	Subject Preference for Self or Partner Administration
Description	A global question was asked: 'If you could choose, which administration method would you like to use on a regular basis?' A) Healthcare professional provided injection B) Self/ partner administered injection
Time Frame	Between week 30 to 34

Outcome Measure Data

Analysis Population Description

Analysis was performed on Intention to Treat population defined as all randomised subjects with ≥ 1 dose of study medication and with a preference assessment recorded

Arm/Group Title	Group 1 Self or Partner First Then HCP Administration	Group 2 HCP Then Self or Partner Administration
Arm/Group Description:	Self or Partner Administration followed by HCP Administration.	Administration by HCP then Self or Partner Administration.
Overall Number of Participants Analyzed	11	14
Measure Type: Number; Unit of Measure: participants
	10	12

2. Secondary Outcome

Title	Number of Patients Stating at Least One Injection Interfered With Daily Activities
Description	The subject was asked: 'Does the treatment administration used today interfere with your daily activities?'
Time Frame	Between baseline to week 32, after each injection (8-9 injections)

Outcome Measure Data

Analysis Population Description

Analysis was performed on Intention to Treat population defined as all randomised subjects with ≥ 1 dose of study medication and with a preference assessment recorded

Arm/Group Title	Training Period	Self or Partner Administration	HCP Administration
Arm/Group Description:	The training period was where the subject or partner performed two or three training injections under supervision of a HCP at a healthcare provider facility.	The self or partner administration block (after training period) included three unsupervised injections every 28th day at the subject's home.	A healthcare administration block included three HCP provided injections according to clinical routine every 28th day at the healthcare provider facility.
Overall Number of Participants Analyzed	25	25	25
Measure Type: Number; Unit of Measure: Participants
	6	2	6

3. Secondary Outcome

Title	Number of Patients Stating at Least One Injection Negatively Interfered With Psychological Wellbeing
Description	The subject was asked: 'Does the treatment administration used today negatively interfere with your psychological wellbeing?'
Time Frame	Between baseline to week 32, after each injection (8-9 injections)

Outcome Measure Data

Analysis Population Description

Analysis was performed on Intention to Treat population defined as all randomised subjects with ≥ 1 dose of study medication and with a preference assessment recorded

Arm/Group Title	Training Period	Self or Partner Administration	HCP Administration
Arm/Group Description:	The training period was where the subject or partner performed two or three training injections under supervision of a HCP at a healthcare provider facility.	The self or partner administration block (after training period) included three unsupervised injections every 28th day at the subject's home.	A healthcare administration block included three HCP provided injections according to clinical routine every 28th day at the healthcare provider facility.
Overall Number of Participants Analyzed	25	25	25
Measure Type: Number; Unit of Measure: participants
	4	2	1

4. Secondary Outcome

Title	Days Sick Leave
Description	Health care and patient costs associated with the treatment of carcinoid symptoms in subjects treated with lanreotide Autogel were assessed through recording loss of production for subject through total number of days sick leave of the employed patients (n=6).
Time Frame	Group 1 - between week 8 to 20 (self or partner administration), between week 20 to 32 (HCP administration). Group 2 - between week 20 to 32 (self or partner administration), between week 0 to week 12 (HCP administration)

Outcome Measure Data

Analysis Population Description

Safety population: all randomised subjects with at least one dose of study medication. Two of the six subjects reported sick leave during the study. One subject was absent for one day due to unknown reason, the other was absent for 22 days due to surgery of metastasis.

Arm/Group Title	Self or Partner Administration	HCP Administration
Arm/Group Description:	The self or partner administration block (after the training period) included three unsupervised injections every 28th day at the subject's home.	A healthcare administration block included three HCP provided injections according to clinical routine every 28th day at the healthcare provider facility.
Overall Number of Participants Analyzed	6	6
Measure Type: Number; Unit of Measure: days
	23	0

5. Secondary Outcome

Title	Total Number of Visits to HCP Due to Carcinoid Symptoms
Description	Health care and patient costs associated with the treatment of carcinoid symptoms in subjects treated with lanreotide Autogel were assessed by recording the total number of visits made by participants (n=12) to HCP due to carcinoid symptoms.
Time Frame	Group 1 - between week 8 to 20 (self or partner administration), between week 20 to 32 (HCP administration). Group 2 - between week 20 to 32 (self or partner administration), between week 0 to week 12 (HCP administration)

Outcome Measure Data

Analysis Population Description

Safety population: all randomised subjects with at least one dose of study medication

Arm/Group Title	Self or Partner Administration	HCP Administration
Arm/Group Description:	The self or partner administration block (after the training) included three unsupervised injections every 28th day at the subject's home.	A healthcare administration block included three HCP provided injections according to clinical routine every 28th day at the healthcare provider facility.
Overall Number of Participants Analyzed	12	12
Measure Type: Number; Unit of Measure: visits
	17	25

6. Secondary Outcome

Title	Perceived Symptom Control Evaluation in Respect to Episodes of Flushing
Description	Participants were asked how they perceived the symptoms in respect to episodes of flushing since the last injection. Participants included in the study were previously treated with lanreotide Autogel and therefore the assessment at baseline was made in comparison to their previous injection outside of the study protocol.
Time Frame	Group 1 - baseline, week 16 to 20 (self or partner administration) and week 30 to 34 (HCP administration). Group 2 - baseline, week 12 (HCP administration) and week 30 (self or partner administration).

Outcome Measure Data

Analysis Population Description

Analysis was performed on Intention to Treat population defined as all randomised subjects with ≥ 1 dose of study medication and with a preference assessment recorded.

Arm/Group Title	Baseline	Self or Partner Administration	HCP Administration
Arm/Group Description:	Baseline refers to the last non-study visit at the clinic.	The self or partner administration block (after training period) included three unsupervised injections every 28th day at the subject's home.	A healthcare administration block included three HCP provided injections according to clinical routine every 28th day at the healthcare provider facility.
Overall Number of Participants Analyzed	25	25	25
Measure Type: Number; Unit of Measure: participants
Worsened	0	1	1
Similar	24	21	20
Improved	1	2	4
Missing	0	1	0

7. Secondary Outcome

Title	Perceived Symptom Control Evaluation in Respect to Episodes of Diarrhoea
Description	Participants were asked how they perceived the symptoms in respect to episodes of diarrhoea since the last injection. Participants included in the study were previously treated with lanreotide autogel and therefore the assessment at baseline was made in comparison to previous injection outside of the study protocol.
Time Frame	Group 1 - baseline, week 16 to 20 (self or partner administration) and week 30 to 34 (HCP administration). Group 2 - baseline, week 12 to 16 (HCP administration) and week 30 to 34 (self or partner administration).

Outcome Measure Data

Analysis Population Description

Analysis was performed on Intention to Treat population defined as all randomised subjects with ≥ 1 dose of study medication and with a preference assessment recorded.

Arm/Group Title	Baseline	Self or Partner Administration	HCP Administration
Arm/Group Description:	Baseline refers to the last non-study visit at the clinic.	The self or partner administration block (after training period) included three unsupervised injections every 28th day at the subject's home.	A healthcare administration block included three HCP provided injections according to clinical routine every 28th day at the healthcare provider facility.
Overall Number of Participants Analyzed	25	25	25
Measure Type: Number; Unit of Measure: participants
Worsened	1	4	0
Similar	22	17	24
Improved	2	3	1
Missing	0	1	0

8. Secondary Outcome

Title	Chromogranin A Levels
Description	Biochemical control was assessed by analysing chromogranin A levels at each site visit, which was mandatory for all subjects. 'Before self or partner administration' was assessed at baseline for group 1 and at week 12 for group 2. 'After self or partner administration' was assessed at week 16 to 20 for group 1 and at week 12 for group 2. 'Before HCP administration' was assessed at week 16 to 20 for group 1 and at baseline for group 2. 'After HCP administration' was assessed at week 30 to 34 for group 1 and week 12 for group 2.
Time Frame	Group 1 - Baseline, week 16 to 20 and 30 to 34. Group 2 - Baseline, week 12 and 30 to 34.

Outcome Measure Data

Analysis Population Description

ITT population that had hormone levels assessed at each administration block.

Arm/Group Title	Before Self or Partner Administration	After Self or Partner Administration	Before HCP Administration	After HCP Administration
Arm/Group Description:	Before self or partner administration block (after training period) which included three unsupervised injections every 28th day at the subject's home.	After the self or partner administration block which included three unsupervised injections every 28th day at the subject's home.	Before the healthcare administration block which included three HCP provided injections according to clinical routine every 28th day at the healthcare provider facility.	After the healthcare administration block which included three HCP provided injections according to clinical routine every 28th day at the healthcare provider facility.
Overall Number of Participants Analyzed	22	22	22	22
Mean (Standard Deviation); Unit of Measure: nmol/l
	37.48 (58.35)	47.85 (74.89)	42.05 (70.74)	37.42 (57.96)

9. Secondary Outcome

Title	5-hydroxyindoleacetic Acid (5-HIAA) Levels
Description	Biochemical control was assessed by analysing 5-HIAA levels at each site visit, which was judged as necessary by the investigator at each site. 'Before self or partner administration' was assessed at baseline for group 1 and at week 12 for group 2. 'After self or partner administration' was assessed at week 16 to 20 for group 1 and at week 12 for group 2. 'Before HCP administration' was assessed at week 16 to 20 for group 1 and at baseline for group 2. 'After HCP administration' was assessed at week 30 to 34 for group 1 and week 12 for group 2.
Time Frame	Group 1 - Baseline, week 16 to 20 and 30 to 34. Group 2 - Baseline, week 12 and 30 to 34.

Outcome Measure Data

Analysis Population Description

5-HIAA were assessed as judged necessary by the investigator at each site.

Arm/Group Title	Before Self or Partner Administration	After Self or Partner Administration	Before HCP Administration	After HCP Administration
Arm/Group Description:	Before self or partner administration block (after training period) which included three unsupervised injections every 28th day at the subject's home.	After the self or partner administration block which included three unsupervised injections every 28th day at the subject's home.	Before the healthcare administration block which included three HCP provided injections according to clinical routine every 28th day at the healthcare provider facility.	After the healthcare administration block which included three HCP provided injections according to clinical routine every 28th day at the healthcare provider facility.
Overall Number of Participants Analyzed	12	12	12	12
Mean (Standard Deviation); Unit of Measure: nmol/l
	220.17 (238.32)	219.17 (227.64)	217.08 (244.32)	219.58 (218.51)

10. Secondary Outcome

Title	Healthcare Professionals With Positive Response to Specified Questions on Self or Partner Administration Method
Description	Assessed by the number of HCP with a positive response 'yes' to two questions: Based on your experience during this trial, did you feel confident in the safety of your patients?; Based on your experience during this trial, would you recommend suitable patients to try self or partner administration?
Time Frame	Between week 30 to 34

Outcome Measure Data

Analysis Population Description

One HCP from each site who enrolled participants replied to the question

Arm/Group Title	Overall Study Group
Arm/Group Description:	One HCP from each site who enrolled participants answered the questions
Overall Number of Participants Analyzed	9
Measure Type: Number; Unit of Measure: participants
	9

Adverse Events

Time Frame	[Not Specified]
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	Training Period		Self or Partner Administration		HCP Administration
Arm/Group Description	The training period was where the subject or partner performed two or three training injections under supervision of a HCP at a healthcare provider facility.		The self or partner administration block (after training period) included three unsupervised injections every 28th day at the subject's home.		A healthcare administration block included three HCP provided injections according to clinical routine every 28th day at the healthcare provider facility.
All-Cause Mortality
	Training Period		Self or Partner Administration		HCP Administration
	Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)
Total	--/--		--/--		--/--
Serious Adverse Events
	Training Period		Self or Partner Administration		HCP Administration
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/26 (15.38%)		4/26 (15.38%)		3/26 (11.54%)
Cardiac disorders
Atrial fibrillation *	0/26 (0.00%)	0	1/26 (3.85%)	1	0/26 (0.00%)	0
Gastrointestinal disorders
Abdominal pain *	0/26 (0.00%)	0	1/26 (3.85%)	1	0/26 (0.00%)	0
Ileus *	2/26 (7.69%)	2	0/26 (0.00%)	0	0/26 (0.00%)	0
Peritoneal cyst *	1/26 (3.85%)	1	0/26 (0.00%)	0	0/26 (0.00%)	0
Subileus *	0/26 (0.00%)	0	0/26 (0.00%)	0	1/26 (3.85%)	1
General disorders
Death *	1/26 (3.85%)	1	0/26 (0.00%)	0	0/26 (0.00%)	0
Disease progression *	0/26 (0.00%)	0	1/26 (3.85%)	1	0/26 (0.00%)	0
Hepatobiliary disorders
Cholangitis *	0/26 (0.00%)	0	0/26 (0.00%)	0	1/26 (3.85%)	2
Infections and infestations
Biliary tract infection *	1/26 (3.85%)	1	0/26 (0.00%)	0	0/26 (0.00%)	0
Infection *	0/26 (0.00%)	0	0/26 (0.00%)	0	1/26 (3.85%)	1
Injury, poisoning and procedural complications
Post procedural fistula *	1/26 (3.85%)	1	0/26 (0.00%)	0	0/26 (0.00%)	0
Respiratory, thoracic and mediastinal disorders
Dyspnoea *	0/26 (0.00%)	0	1/26 (3.85%)	1	0/26 (0.00%)	0
* Indicates events were collected by non-systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Training Period		Self or Partner Administration		HCP Administration
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	7/26 (26.92%)		4/26 (15.38%)		7/26 (26.92%)
Gastrointestinal disorders
Nausea *	3/26 (11.54%)	4	1/26 (3.85%)	1	0/26 (0.00%)	0
General disorders
Disease progression *	0/26 (0.00%)	0	1/26 (3.85%)	2	2/26 (7.69%)	2
Injection site pain *	4/26 (15.38%)	4	1/26 (3.85%)	3	3/26 (11.54%)	6
Nervous system disorders
Headache *	3/26 (11.54%)	4	1/26 (3.85%)	1	0/26 (0.00%)	0
Vascular disorders
Flushing *	0/26 (0.00%)	0	1/26 (3.85%)	2	2/26 (7.69%)	2
* Indicates events were collected by non-systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS 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: Medical Director, Endocrinology
• Organization: Ipsen
• Phone: clinical.trials@ipsen.com
• EMail: clinical.trials@ipsen.com

• Responsible Party: Ipsen
• ClinicalTrials.gov Identifier: NCT00681187
• Other Study ID Numbers: A-99-52030-216; 2007-006514-42 ( EudraCT Number )
• First Submitted: May 19, 2008
• First Posted: May 21, 2008
• Results First Submitted: September 1, 2011
• Results First Posted: March 13, 2012
• Last Update Posted: November 22, 2019