Clinical trial NCT03012594
Conditions: Gastrointestinal Motility Disorder Intestinal Disease
Keywords: Small bowel motility disorder Slow intestinal motility Small bowel bacterial overgrowth
Sponsor: Northwell Health
Start date: 2017-05-11; Completion date: 2019-03-11
Enrollment: 12 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
This is a human research study looking at the effectiveness of Lanreotide (study medication) in treating small bowel motility disorders. It is similar to a natural hormone somatostatin that is produced in the body in the stomach, duodenum, pancreas and brain. Somatostatin is a growth hormone-inhibiting hormone. Lanreotide is a man made hormone and is a long acting medication that is given once a month. It is marketed with a trade name "Somatuline Depot". It is given deep subcutaneously (deep within the layers of the skin) in the superior external quadrant of the buttock. Injection site will be alternated on subsequent injections.

Detailed description:
The investigators hypothesize that in patients with small bowel motility disorders, Lanreotide helps in alleviating the symptoms. Lanreotide is an FDA approved medication for management of acromegaly and neuroendocrine tumors, but has never been used for treating small bowel motility disorders. However, Octreotide which is similar to Lanreotide but is a short acting synthetic somatostatin has been used in few research studies.

If a patient is interested and qualifies for the study then he/she will be explained about the study and signature will be collected on the consent form. Health and social history will be collected. Blood work, urine analysis, pregnancy test (in women of reproductive age group and have the capability of getting pregnant)) will be performed to make sure that patient qualifies for the study and for follow-up during the treatment. Physical examination, ECG, wireless motility capsule testing and hydrogen breath testing will be performed. Patients will be required to complete a questionnaire regarding their health.

The total study duration from the first administration of study drug is 12 weeks. The study medication will be given once a month for 3 months and there is a 1 month follow-up after the last study medication. There will be a screening visit approximately 1 month before the first study drug administration.

Arms: arm 1: Open label
Interventions: intervention 1: Lanreotide
Intervention descriptions: intervention 1: Dosage: 120mg Dosage form: subcutaneous injection, pre-filled syringe Dosage frequency: 3 injections over 12 weeks, each dose administered 4 weeks apart

Protocol documents:
Prot_SAP_000.pdf: 
 
 
Page 1 of 42 
NCT NUMBER: - NCT03012594  
DATE: - OCTOBER 28TH, 2016 
 
This document is confidential and the property of the Northwell Health System.  No part of 
it may be transmitted, reproduced, published, or used by other persons without prior 
written authorization from the study sponsor. 
 
 
 
 
 
 
 
 
 
 
A PILOT STUDY TO EVALUATE SAFETY AND EFFECTIVENESS OF 
LANREOTIDE IN THE TREATMENT OF PATIENTS WITH SMALL 
BOWEL MOTILITY DISORDERS (SBMD): A PROSPECTIVE, NON-
RANDOMIZED, SINGLE CENTER STUDY OF 20 PARTICIPANTS.  
 
 
 
 
 
NCT NUMBER: - NCT03012594 
 
DATE: - OCTOBER 28TH, 2016 
 
STUDY PRODUCT: SOMATULINE DEPOT (LANREOTIDE) 
CONFIDENTIAL 
 
 
 
 
 
 
 
 
 
 
 
 
 


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NCT NUMBER: - NCT03012594 
 
DATE: - OCTOBER 28TH, 2016 
 
This document is confidential and the property of the Northwell Health System.  No part of 
it may be transmitted, reproduced, published, or used by other persons without prior 
written authorization from the study sponsor. 
  
List of Abbreviations 
 
AE 
adverse event 
ALT 
alanine aminotransferase 
AST 
aspartate aminotransferase 
b.i.d. 
twice a day 
CRF 
Case Report/Record Form 
CRD 
Clinical Research and Development 
CPO 
Country Pharma Organization 
CRO 
Contract Research Organization 
CSR 
Clinical Study Report 
ECG 
Electrocardiogram 
FDA 
Food and Drug Administration 
ICH 
International Conference on Harmonization of Technical Requirements for 
Registration of Pharmaceuticals for Human Use 
IEC 
Independent Ethics Committee 
IMS 
Integrated Medical Safety 
i.v. 
intravenous(ly) 
IRB 
Institutional Review Board 
IVRS 
Interactive Voice Response System  
o.d. 
once a day 
PAGI-SYM  
Patient Assessment of upper GastroIntestinal disorders-symptom severity index 
p.o. 
oral(ly) 
REB 
Research Ethics Board 
SAE 
serious adverse event 
SBMD 
Small Bowel Motility Disorder 
WMC 
Wireless Motility Capsule 
 
 
 


Page 3 of 42 
 
NCT NUMBER: - NCT03012594 
 
DATE: - OCTOBER 28TH, 2016 
 
This document is confidential and the property of the Northwell Health System.  No part of 
it may be transmitted, reproduced, published, or used by other persons without prior 
written authorization from the study sponsor. 
 
1 Previous Study History 
Has this study ever been reviewed and rejected/disapproved by another IRB prior to 
submission to this IRB? 
 
 No  
 Yes −  if yes, please explain:  
 
2 Brief Summary of Research 
 
This is a human research study looking at the effectiveness of Lanreotide (study medication) in 
treating small bowel motility disorders. It is similar to a natural hormone somatostatin that is 
produced in the body in the stomach, duodenum, pancreas and brain. Somatostatin is a growth 
hormone-inhibiting hormone. Lanreotide is a man made hormone and is a long acting medication 
that is given once a month. It is marketed with a trade name “Somatuline Depot”. It is given deep 
subcutaneously (deep within the layers of the skin) in the superior external quadrant of the 
buttock. Injection site will be alternated on subsequent injections. 
 
We hypothesize that in patients with small bowel motility disorders, Lanreotide helps in 
alleviating the symptoms. Lanreotide is an FDA approved medication for management of 
acromegaly and neuroendocrine tumors, but has never been used for treating small bowel 
motility disorders. However Octreotide which is similar to lanreotide but is a short acting 
synthetic somatostatin has been used in few research studies.  
 
If a patient is interested and qualifies for the study then he/she will be explained about the study 
and signature will be collected on the consent form. Health and social history will be collected. 
Blood work, urine analysis, pregnancy test (in women of reproductive age group and have the 
capability of getting pregnant)) will be performed to make sure that patient qualifies for the study 
and for follow-up during the treatment. Physical examination, ECG, wireless motility capsule 
testing and hydrogen breath testing will be performed. Patients will be required to complete a 
questionnaire regarding their health.  
 
The total study duration from the first administration of study drug is 12 weeks. The study 
medication will be given once a month for 3 months and there is a 1 month follow-up after the 
last study medication. There will be a screening visit approximately 1 month before the first 
study drug administration.  
 
 
3 Introduction 
 
This document is a clinical research protocol. This study is to be conducted according to US and 


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NCT NUMBER: - NCT03012594 
 
DATE: - OCTOBER 28TH, 2016 
 
This document is confidential and the property of the Northwell Health System.  No part of 
it may be transmitted, reproduced, published, or used by other persons without prior 
written authorization from the study sponsor. 
international standards of Good Clinical Practice (FDA Title 21 part 312 and International 
Conference on Harmonization guidelines), applicable government regulations and Institutional 
research policies and procedures. 
3.1 Background 
 
Small bowel motility disorder (SBMD) is characterized by signs and symptoms of a mechanical 
obstruction in the flow of intestinal contents, without any presence of an anatomic lesion. It may 
be acute or chronic, and imaging shows dilation of the bowel on imaging. It is postulated to be 
due to an underlying neuropathic disorder, a myopathic disorder, or abnormality in the interstitial 
cell of Cajal. Approximately a half of the cases are secondary to neurologic, paraneoplastic, 
autoimmune, metabolic/endocrine, and infectious diseases.(4) 
This condition is considered rare and reports estimating the incidence and prevalence mostly 
originate from tertiary referral centers. For example, a nation-wide survey in Japan has estimated 
the prevalence as 0.80 to 1.00 per 100,000 with an incidence of 0.21 to 0.24 per 100,000. The 
mean age at diagnosis was 63.1 years for males and 59.2 for females.(5) The prognosis is very 
poor in children, with majority of them requiring parenteral nutrition with mortality rate ranging 
from 10 to 25 percent.(6) In adults, the majority of patients suffer nutritional compromise, and 
about a third requiring long-term parenteral nutrition.(7) Complications secondary to parenteral 
nutrition are seen in 45-80 percent and mortality rate approaches 10 percent.(8)  
Patients with SBMD may require supplemental nutrition. Prokinetics are used for acute and 
chronic therapy, antibiotics are recommended when small bowel bacterial overgrowth is 
suspected, and immunomodulator therapy is typically reserved for an established underlying 
inflammatory neuropathy. Surgery is only performed if needed to provide access 
for venting/feeding, and resection or bypass of localized disease of the small bowel is avoided. 
Intestinal transplantation may be indicated when long-term parenteral nutrition cannot be 
initiated or continued safely.(9) 
As a prokinetic, short-acting somatostatin analogue octreotide has been one of the few options in 
treating SBMD. Long-acting Lanreotide Depot (Autogel), with its 4-weekly dosing regimen, 
may improve the efficacy of treatment by enhancing patient compliance.(10)  
Lanreotide (1, 11, 12) is a somatostatin analogue, like octreotide, but with known long acting 
small bowel prokinetic property, and can be very effective in treating small bowel motility 
disorders. Lanreotide has been approved by FDA(See attachment 1) for the treatment of well 
differentiated neuroendocrine tumors of low and intermediate grade. According to Lexicomp, its 
safety profile has been established and most adverse reactions such as bradycardia and 
cholelithiasis can be easily monitored. 
 


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NCT NUMBER: - NCT03012594 
 
DATE: - OCTOBER 28TH, 2016 
 
This document is confidential and the property of the Northwell Health System.  No part of 
it may be transmitted, reproduced, published, or used by other persons without prior 
written authorization from the study sponsor. 
3.2 Investigational Agent 
 
---------------------------INDICATIONS AND USAGE------------------------ 
SOMATULINE DEPOT (lanreotide) Injection is a somatostatin analog indicated for: 
• The long-term treatment of acromegalic patients who have had an inadequate response to 
or cannot be treated with surgery and/or radiotherapy. 
• The treatment of patients with unresectable, well- or moderately-differentiated, locally 
advanced or metastatic gastroenteropancreatic neuroendocrine tumors (GEP-NETs) to 
improve progression-free survival. 
----------------------DOSAGE AND ADMINISTRATION-------------------- 
• Injected in the superior external quadrant of the buttock. Injection site should be 
alternated.  
Acromegaly  
• Dose range is 60 mg to 120 mg every 4 weeks. Recommended starting dose is 90 mg 
every 4 weeks for 3 months. Adjust thereafter based on GH and/or IGF-1 levels. 
• Moderate and Severe Renal and Hepatic Impairment: Initial dose is 60 mg every 4 weeks 
for 3 months. Adjust thereafter based on GH and/or IGF-1 levels. 
GEP-NET 
• 
Recommended dose is 120 mg every 4 weeks. 
---------------------DOSAGE FORMS AND STRENGTHS------------  
• Injection: 60 mg/0.2 mL, 90 mg/0.3 mL, and 120 mg/0.5 mL single-use prefilled syringes 
-------------------------------CONTRAINDICATIONS-------------------------- 
• Hypersensitivity to lanreotide 
-----------------------WARNINGS AND PRECAUTIONS--------------------- 
• Gallbladder: Gallstones may occur; consider periodic monitoring 
• Glucose Metabolism: Hypo- and/or hyperglycemia may occur. Glucose monitoring is 


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NCT NUMBER: - NCT03012594 
 
DATE: - OCTOBER 28TH, 2016 
 
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it may be transmitted, reproduced, published, or used by other persons without prior 
written authorization from the study sponsor. 
recommended and antidiabetic treatment adjusted accordingly 
• Cardiac Function: Decrease in heart rate may occur. Use with caution in at-risk patients 
 
-----------------------------ADVERSE REACTIONS----------------------------- 
• Acromegaly: Most common adverse reactions are diarrhea, cholelithiasis, abdominal 
pain, nausea and injection site reactions 
• GEP-NET: Most common adverse reactions (>10%) are abdominal  
• pain, musculoskeletal pain, vomiting, headache, injection site reaction, hyperglycemia, 
hypertension, cholelithiasis 
----------------------------DRUG INTERACTIONS------------------------------ 
• Hypoglycemia agents: Hypo- and/or hyperglycemia may occur. Glucose monitoring is 
recommended and antidiabetic treatment adjusted accordingly 
• Cyclosporine: Somatuline may decrease the bioavailability of cyclosporine. Cyclosporine 
dose may need to be adjusted 
• Drugs affecting heart rate:  Somatuline may decrease heart rate.  Dose adjustment of 
coadministered drugs may be necessary 
-----------------------USE IN SPECIFIC POPULATIONS--------------------- 
• Renal Impairment: Start dose is 60 mg for patients with acromegaly and moderate and 
severe renal impairment 
• Hepatic Impairment: Start dose is 60 mg for patients with acromegaly and moderate and 
severe hepatic impairment 
 
 
3.3 Preclinical Data 
 
Essential nonclinical pharmacology, toxicology and PK were initially performed to support 
the MPF formulation. Subsequent studies have assessed the nonclinical safety and PK profile 
of the Autogel formulation. Toxicology data have been assessed based on serum lanreotide 
concentrations in animals compared with humans after administration of lanreotide Autogel 
120 mg (1.7 mg/kg based on body weight of 70 kg). Based upon the pharmacology, PK and 


Page 7 of 42 
 
NCT NUMBER: - NCT03012594 
 
DATE: - OCTOBER 28TH, 2016 
 
This document is confidential and the property of the Northwell Health System.  No part of 
it may be transmitted, reproduced, published, or used by other persons without prior 
written authorization from the study sponsor. 
toxicology studies (including cardiovascular tolerance), lanreotide Autogel is considered to be 
safe for chronic use in humans. 
Additional PK and local tolerance studies of lanreotide PRF have been performed to support 
this new development formulation. Furthermore, because limited information is available on 
the excipient glycofurol that is used in this formulation a dedicated program to evaluate its 
toxicity has been initiated. 
 
Please see additional information in the Lanreotide Investigators Brochure. (Attachment 2) 
 
3.4 Clinical Data to Date 
 
14.1 Acromegaly 
The effect of SOMATULINE DEPOT on reducing GH and IGF-levels and control of symptoms 
in patients with acromegaly was studied in two long-term, multiple-dose, randomized, 
multicenter studies. 
Study 1 
This one-year study included a 4-week, double-blind, placebo-controlled phase; a 16-week 
single-blind, fixed-dose phase; and a 32-week, open-label, dose-titration phase.  Patients with 
active acromegaly, based on biochemical tests and medical history, entered a 12-week washout 
period if there was previous treatment with a somatostatin analog or a dopaminergic agonist.   
Upon entry, patients were randomly allocated to receive a single, deep subcutaneous injection of 
SOMATULINE DEPOT 60 mg, 90 mg, or 120 mg or placebo. Four weeks later, patients entered 
a fixed-dose phase where they received 4 injections of SOMATULINE DEPOT followed by a 
dose-titration phase of 8 injections for a total of 13 injections over 52 weeks (including the 
placebo phase).  Injections were given at 4-week intervals. During the dose-titration phase of the 
study, the dose was titrated twice (every fourth injection), as needed, according to individual GH 
and IGF-1 levels.  
A total of 108 patients (51 males, 57 females) were enrolled in the initial placebo-controlled 
phase of the study. Half (54/108) of the patients had never been treated with a somatostatin 
analog or dopamine agonist, or had stopped treatment for at least 3 months prior to their 
participation in the study and were required to have a mean GH level > 5 ng/mL at their first 
visit. The other half of the patients had received prior treatment with a somatostatin analog or a 
dopamine agonist before study entry and at study entry were required to have a mean GH 
concentration >3 ng/mL and at least a 100% increase in mean GH concentration after washout of 
medication. 
One hundred and seven (107) patients completed the placebo-controlled phase, 105 patients 
completed the fixed-dose phase, and 99 patients completed the dose-titration phase. Patients not 
completing withdrew due to adverse events (5) or lack of efficacy (4). 
In the double-blind phase of study 1, a total of 52 (63%) of the 83 lanreotide-treated patients had 


Page 8 of 42 
 
NCT NUMBER: - NCT03012594 
 
DATE: - OCTOBER 28TH, 2016 
 
This document is confidential and the property of the Northwell Health System.  No part of 
it may be transmitted, reproduced, published, or used by other persons without prior 
written authorization from the study sponsor. 
a > 50% decrease in mean GH from baseline to Week 4, including 52%, 44%, and 90% of 
patients in the 60 mg, 90 mg, and 120 mg groups, respectively, compared to placebo (0%, 0/25).  
In the fixed-dose phase at Week 16, 72% of all 107 lanreotide-treated patients had a decrease 
from baseline in mean GH of > 50%, including 68% (23/34), 64% (23/36), and 84% (31/37) of 
patients in the 60 mg, 90 mg, and 120 mg lanreotide treatment groups, respectively. Efficacy 
achieved in the first 16 weeks was maintained for the duration of the study (see Table 4). 
 
Table 4: Overall Efficacy Results Based on GH and IGF-1 Levels by Treatment Phase in Study 1 
 
Baseline 
 
 
N=107 
Before  
Titration 1 
(16 weeks) 
N=107 
Before  
Titration 2 
(32 weeks) 
N=105 
Last Value 
 
N=1
GH 
≤5.0 ng/mL 
Number of 
Responders (%) 
20 
(19%) 
72 
(67%) 
76 
(72%) 
74
(69%
≤2.5 ng/mL 
Number of 
Responders (%) 
0 
(0%) 
52 
(49%) 
59 
(56%) 
55
(51%
≤1.0 ng/mL 
Number of 
Responders (%) 
0 
(0%) 
15 
(14%) 
18 
(17%) 
17
(16%
Median GH 
ng/mL 
10.27 
2.53 
2.20 
2.4
GH Reduction 
Median % 
Reduction 
-- 
75.5 
78.2 
75
IGF-1 
Normal3 
Number of 
Responders (%) 
9 
(8%) 
58 
(54%) 
57 
(54%) 
62
(58%
Median IGF-1 
ng/mL 
775.0 
332.01 
316.52 
326
IGF-1 Reduction 
Median % 
Reduction  
-- 
52.31 
54.52 
55
IGF-1 Normal3 + 
GH ≤2.5 ng/mL 
 
Number of 
Responders (%) 
0 
(0%) 
41 
(38%) 
46 
(44%) 
44
(41%
1n=105, 2n=102, 3Age-adjusted,  *Last Observation Carried Forward 
 
Study 2 
This was a 48-week, open-label, uncontrolled, multicenter study that enrolled patients who had 
an IGF-1 concentration ≥ 1.3 times the upper limit of the normal age-adjusted range. Patients 
receiving treatment with a somatostatin analog (other than SOMATULINE DEPOT) or a 
dopaminergic agonist had to attain this IGF-1 concentration after a washout period of up to 3 
months. 
Patients were initially enrolled in a 4-month, fixed-dose phase where they received 4 deep 
subcutaneous injections of SOMATULINE DEPOT 90 mg, at 4-week intervals. Patients then 
entered a dose-titration phase where the dose of SOMATULINE DEPOT was adjusted based on 
GH and IGF-1 levels at the beginning of the dose-titration phase and, if necessary, again after 
another 4 injections. Patients titrated up to the maximum dose (120 mg) were not allowed to 
titrate down again.  


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NCT NUMBER: - NCT03012594 
 
DATE: - OCTOBER 28TH, 2016 
 
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it may be transmitted, reproduced, published, or used by other persons without prior 
written authorization from the study sponsor. 
A total of 63 patients (38 males, 25 females) entered the fixed-dose phase of the trial and 57 
patients completed 48 weeks of treatment. Six patients withdrew due to adverse reactions (3), 
other reasons (2), or lack of efficacy (1). 
After 48 weeks of treatment with SOMATULINE DEPOT at 4-week intervals, 43% (27/63) of 
the acromegalic patients in this study achieved normal age-adjusted IGF-1 concentrations. Mean 
IGF-1 concentrations after treatment completion were 1.3 ± 0.7 times the upper limit of normal 
compared to 2.5 ± 1.1 times the upper limit of normal at baseline. 
The reduction in IGF-1 concentrations over time correlated with a corresponding marked 
decrease in mean GH concentrations. The proportion of patients with mean GH concentrations < 
2.5 ng/mL increased significantly from 35% to 77% after the fixed-dose phase and 85% at the 
end of the study. At the end of treatment, 24/63 (38%) of patients had both normal IGF-1 
concentrations and a GH concentration of ≤ 2.5 ng/mL (see Table 5) and 17/63 patients (27%) 
had both normal IGF-1 concentrations and a GH concentration of <1 ng/mL.   
Table 5: Overall Efficacy Results Based on GH and IGF-1 Levels by Treatment Phase in Study 2 
 
Baseline 
 
 
N=63 
Before  
Titration 1 
(12 wks) 
N=63 
Before  
Titration 2 
(28 wks) 
N=59 
Last Value Ava
 
N=63 
IGF-1 
Normal1 
Number of 
Responders (%) 
0 
(0%) 
17 
(27%) 
22 
(37%) 
27 
(43%) 
Median IGF-1 
ng/mL 
689.0 
382.0 
334.0 
317.0 
IGF-1 Reduction 
Median % Reduction 
-- 
41.0 
51.0 
50.3 
GH 
≤5.0 ng/mL 
Number of 
Responders (%) 
40 
(64%) 
59 
(94%) 
57 
(97%) 
62 
(98%) 
≤2.5 ng/mL 
Number of 
Responders (%) 
21 
(33%) 
47 
(75%) 
47 
(80%) 
54 
(86 %) 
≤1.0 ng/mL 
Number of 
Responders (%) 
8 
(13%) 
19 
(30%) 
18 
(31%) 
28 
(44%) 
Median GH 
ng/mL 
3.71 
1.65 
1.48 
1.13 
GH Reduction 
Median % Reduction 
-- 
63.2 
66.7 
78.62 
IGF-1 normal1 + 
GH ≤2.5 ng/mL 
 
Number of 
Responders (%) 
0 
(0%) 
14 
(22%) 
20 
(34%) 
24 
(38%) 
1Age-adjusted, 2N= 62, *Last Observation Carried Forward 
Examination of age and gender subgroups did not identify differences in response to 
SOMATULINE DEPOT among these subgroups. The limited number of patients in the different 
racial subgroups did not raise any concerns regarding efficacy of SOMATULINE DEPOT in 
these subgroups. 
14.2 Gastroenteropancreatic Neuroendocrine Tumors 
The efficacy of SOMATULINE DEPOT was established in a multicenter, randomized, double-
blind, placebo-controlled trial of 204 patients with unresectable, well or moderately 
differentiated, metastatic or locally advanced, gastroenteropancreatic neuroendocrine tumors. 


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NCT NUMBER: - NCT03012594 
 
DATE: - OCTOBER 28TH, 2016 
 
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it may be transmitted, reproduced, published, or used by other persons without prior 
written authorization from the study sponsor. 
Patients were required to have non-functioning tumors without hormone-related symptoms. 
Patients were randomized 1:1 to receive SOMATULINE DEPOT 120 mg (n=101) or placebo 
(n=103) every 4 weeks until disease progression, unacceptable toxicity or a maximum of 96 
weeks of treatment. Randomization was stratified by the presence or absence of prior therapy 
and by the presence or absence of disease progression within 6 months of enrollment. The major 
efficacy outcome measure was progression-free survival (PFS), defined as time to disease 
progression as assessed by central independent radiological review using the Response 
Evaluation Criteria in Solid Tumors (RECIST 1.0), or death.  
The median patient age was 63 years (range 30-92 years) and 95% were Caucasian.  Disease 
progression was present in nine of 204 patients (4.4%) in the 6 months prior to enrollment and 
twenty-nine patients (14%) received prior chemotherapy.  Ninety-one patients (45%) had 
primary sites of disease in the pancreas, with the remainder originating in the midgut (35%), 
hindgut (7%), or unknown primary location (13%).  The majority (69%) of the study population 
had grade 1 tumors. Baseline prognostic characteristics were similar between arms with one 
exception; there were 39% of patients in the SOMATULINE DEPOT arm and 27% of patients in 
the placebo arm who had hepatic involvement by tumor of > 25%.   
Patients on the SOMATULINE DEPOT arm had a statistically significant improvement in 
progression-free survival compared to patients receiving placebo (see Table 6 and Figure 1).   
 
Table 6: Efficacy Results in Study 3 
 
  
SOMATULINE DEPOT 
Placebo 
  
n = 101 
n = 103 
Number of Events (%) 
32 (31.7%) 
60 (58.3%) 
Median PFS (months)(95% CI) 
NE1 (NE, NE) 
16.6 (11.2, 22.1) 
HR (95% CI) 
0.47 (0.30, 0.73)2 
Log-rank p-value 
< 0.001 
1: NE = not reached at 22 months 
2: Hazard Ratio is derived from a Cox stratified proportional hazards model  
 
 
 
Figure 1: Kaplan-Meier Curves of Progression-Free Survival  


Page 11 of 42 
 
NCT NUMBER: - NCT03012594 
 
DATE: - OCTOBER 28TH, 2016 
 
This document is confidential and the property of the Northwell Health System.  No part of 
it may be transmitted, reproduced, published, or used by other persons without prior 
written authorization from the study sponsor. 
 
Please see additional information in the Lanreotide Investigators Brochure. (Attachment 2) 
 
 
3.5 Dose Rationale and Risk/Benefits 
 
There has not been an effective treatment for SBMD, especially in patients with delayed small 
bowel transit time accompanied by abdominal bloating.  
Somatostatin is a peptide hormone that regulates the endocrine system and affects 
neurotransmission and cell proliferation via interaction with G protein-coupled somatostatin 
receptors and inhibition of the release of numerous secondary hormones. It is widely distributed 
in the central nervous system, gastrointestinal tract, and endocrine cells. It modulates many 
physiological processes, such as pro-absorption, anti-secretion, anti-proliferation, immunological 
modulation, neuronal excitability, and vascular smooth muscle contractility. In the intestine, 
somatostatin is known to affect intestinal motility, to reduce secretion, and to stimulate water and 
sodium absorption(1, 10, 13). 
While octreotide, is a short-acting somatostatin and has been used with moderate success, it 
suffers from the short serum bioavailability requiring frequent administrations (half life of 100 


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DATE: - OCTOBER 28TH, 2016 
 
This document is confidential and the property of the Northwell Health System.  No part of 
it may be transmitted, reproduced, published, or used by other persons without prior 
written authorization from the study sponsor. 
minutes). 
As an analogue to somatostatin, lanreotide is known for its prokinetic properties, and it is also 
long-acting, making it a desired alternative to the current treatment regime using short-acting 
octreotide. This study will investigate the usefulness of lanreotide in the treatment of SBMD, as 
measured by small bowel transit time in wireless motility capsule testing. This is a pilot, non-
randomized, unblinded study and there is no placebo in the study. 
The results from both single dose administration and four dose administrations suggested a 
dose-response relationship between lanreotide treatment and GH concentration control. At 
higher doses of lanreotide Autogel, greater proportions of patients had at least a 50% 
reduction from baseline in mean serum GH concentration. Additionally, a greater proportion 
of patients (regardless of the treatment group) had at least a 50% reduction in GH concentration 
after receiving four dose administrations than after receiving a single dose. The long-term open-
label dose titration periods of two studies (14) provide pivotal data about the optimal control of 
patients with lanreotide Autogel following titration of the monthly dose for more than 6 months. 
The combined analysis of the dose titration periods of Studies shows that patients with 
acromegaly achieved long-term optimal hormonal control as defined by GH and IGF-1 
concentrations. 
 
1. This study is not intended to be reported to FDA in support of a new indication for use or to 
support any other significant change in the labeling for the drug. 
2. This study is not intended to support a significant change in the advertising for the product. 
3. This study does not involve a route of administration or dosage level, use in a subject 
population, or other factor that significantly increases the risk (or decreases the acceptability of 
the risk) associated with the use of the drug. 
4. This study is conducted in compliance with the requirements for Institutional Review 
Board/Independent Ethics Committee (IRB/IEC) review and informed consent. 
5. This study is conducted in compliance with the requirements concerning the promotion and 
sale of drugs. 
6. This study does not intend to invoke 21 CFR 50.24 (exception from informed consent for 
emergency research)." 
 
This study satisfies all the above criteria and hence it is not required to submit an IND to FDA. 
 
Please see additional information in the Lanreotide Investigators Brochure. (Attachment 2) 
 
4 Study Objectives 
 


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it may be transmitted, reproduced, published, or used by other persons without prior 
written authorization from the study sponsor. 
Primary objective/s 
The primary objective is to identify if lanreotide will help in alleviating the effects of small 
bowel motility disorders. Effect of lanreotide on small bowel motility disorder will be assessed 
in 20 patients by looking at small bowel transit time using wireless motility capsule (SmartPill) 
testing. Achieving small bowel transit time of less than 6 hrs will be considered as a positive 
response. 
Secondary objective/s 
1. Improvement in symptoms as assessed by symptom questionnaire (Eg: - improvement in 
nausea, vomiting, abdominal pain, bloating), improvement in upper gastrointestinal disorders-
symptom severity index (PAGI-SYM) scores. 
2. Resolution of small intestinal bacterial overgrowth as assessed by hydrogen breath testing.  
 
5 Resources Available to Conduct the Human Research 
All the three hospitals included as sites in the study are tertiary care centers with well known 
gastroenterology departments. Thousands of patients are treated each year in these hospitals with 
various gastroenterological conditions. These hospitals are also one of the leading referral 
centers for gastroenterological conditions in Manhattan and in Long island. Even though the 
condition being addressed in this study is rare, we anticipate no problem in recruiting due to the 
large patient population and referral base.  
The gastroenterology department has the capability, facilities and personnel to perform all the 
procedures that are described in this research study. 
All research personnel involved in the study are required to complete the essential requirements 
for participation in the study (e.g.: CITI trainings (Human research section, Conflict of interest)). 
All study personnel will be required to complete the delegation log describing their roles in the 
project. 
6 Study Design 
6.1 General Design 
 
This is a pilot, single center, single arm, open-label, non-randomized, prospective study of 
consecutive patients with small bowel motility disorder.  
 
 
 
Screening 
(≤30 days) and 
-15 days ((± 7 
days) 
Day 0 
Week 2 
(± 4 days) 
Week 4 
(± 7 days) 
Week 6 
(± 7 days) 
Week 8 
(± 7 days) 
Week 12 
(± 7 days) 
• 
Consent 
• 
Medical 
history 
• 
Inclusion/Excl
usion criteria 
• 
Physical exam 
• 
Vitals 
• 
ECG 
• 
Questionnaire 
• 
Blood glucose 
• 
Lab 
evaluations
• 
Short 
Physical 
exam 
• 
Medicatio
n history 
• 
Vitals 
• 
Questionn
aire 
• 
Medication 
history 
• 
Vitals 
• 
AE 
assessment
• 
Short 
Physical 
exam 
• 
Medicatio
n history 
• 
Vitals 
• 
AE 
assessment 
• 
Medication 
history 
• 
Vitals 
• 
AE 
assessment
• 
Short 
Physical 
exam 
• 
Medication 
history 
• 
Vitals 
• 
AE 
assessment 
• 
Medication 
history 
• 
Vitals 
• 
AE 
assessment 
• 
Questionna
ire 
• 
Blood 


Page 14 of 42 
 
NCT NUMBER: - NCT03012594 
 
DATE: - OCTOBER 28TH, 2016 
 
This document is confidential and the property of the Northwell Health System.  No part of 
it may be transmitted, reproduced, published, or used by other persons without prior 
written authorization from the study sponsor. 
 
 
 
 
 
 
 
 
 
 
Study set-up will take approximately 2-3 months, enrollment period for 6 months, treatment 
duration for 8-12 weeks, follow up for 1 month post treatment, and manuscript 
preparation/submission for 2 months. 
1 Performed only if the tests are not performed in the last 2 months as standard of care. 
 
6.2 Primary Study Endpoints 
 
• Effect of lanreotide on small bowel motility disorders, as assessed by small bowel transit 
time using wireless motility capsule (SmartPill) testing. If the small bowel transit time, as 
measured by wireless capsule endoscopy, is decreased to < 6hrs, then patient would be 
considered a responder and that lanreotide is efficacious. % of responder would be 
reported as endpoint. We expect >50% patients to be responders. 
 
6.3 Secondary Study Endpoints 
 
• Improvement in symptoms as assessed by improvement in upper gastrointestinal 
disorders-symptom severity index (PAGI-SYM) scores. PAGI-SYM is a brief (20-items 
with 6 sub scales) symptom severity questionnaire that captures information on common 
upper gastrointestinal symptoms, including heartburn, regurgitation, fullness, early 
satiety, bloating, nausea and vomiting, and upper abdominal pain. If the PAGI-Sym 
scores were decreased by at least 0.7 points compared to pre treatment, then it will be 
considered that lanreotide has significantly improved the symptom severity. (15-17) 
 


Page 15 of 42 
 
NCT NUMBER: - NCT03012594 
 
DATE: - OCTOBER 28TH, 2016 
 
This document is confidential and the property of the Northwell Health System.  No part of 
it may be transmitted, reproduced, published, or used by other persons without prior 
written authorization from the study sponsor. 
• Resolution of small intestinal bacterial overgrowth as assessed by hydrogen breath 
testing. If the hydrogen breath test is positive (>20 ppm from the baseline) before 
treatment and it decreases (changes to <20 from the baseline) after treatment, it will be 
considered that lanreotide is efficacious in decreasing the small intestinal bacterial 
overgrowth. 
 
6.4 Primary Safety Endpoints 
 
• Cardiac Function  (Bradycardia (Decreased heart rate) and hypertension) - If the subjects 
heart rate decreases by more than 20%, and either systolic or diastolic pressures increase 
by more than 20% during any of the visits when compared to that of the screening visit. 
• Cholelithiasis (Gallstones)- Symptoms include severe right upper quadrant abdominal 
pain , nausea and vomiting, abdominal tenderness, clay colored stools, Jaundice 
(yellowing of skin and whites of the eye).   
• Glucose Metabolism - (Hyperglycemia or hypoglycemia) – Blood glucose will be 
monitored during every visit. If there is a variation of more than 20% then it is considered 
as a safety end point.   
• Acute anaphylactic reactions – If the subjects develops anaphylactic reaction then he/she 
will be removed from the study and will be monitored and treated as per standard of care.   
• Pancreatitis – It is characterized by Upper abdominal pain that radiates into the back; it 
may be aggravated by eating, especially foods high in fat, Swollen and tender abdomen, 
Nausea and vomiting, Fever and Increased heart rate. Signs of pancreatitis will be 
checked for during every visit.   
• Hepatitis – Signs of hepatitis include Loss of appetite, Nausea and vomiting, Diarrhea, 
Dark-colored urine and pale bowel movements, Stomach pain and Jaundice (yellowing of 
skin and eyes). Signs of hepatitis will be checked for during every visit.  
• Thyroid Function Abnormalities - If there is a variation of more than 20% from the 
screening visit values of T3, T4, TSH and if the subject is on any other thyroid 
medication that might have caused this, then the subject will be referred to her 
endocrinologist for dose adjustment. If the change occurred without any concomitant 
medication then the subject will be removed from the study and will be monitored and 
treated as per standard of care. 
 
7 Subject Selection and Withdrawal 
7.1 Inclusion Criteria 
 
1. Consecutive patients with evidence of small bowel motility disorders, referred to (or) are 
patients of the Gastroenterology and Motility Center at Northwell health system. 
2. Aged between 18 and 70 years. 


Page 16 of 42 
 
NCT NUMBER: - NCT03012594 
 
DATE: - OCTOBER 28TH, 2016 
 
This document is confidential and the property of the Northwell Health System.  No part of 
it may be transmitted, reproduced, published, or used by other persons without prior 
written authorization from the study sponsor. 
3. Subjects should be capable of understanding the study and be able to give informed consent. 
4. Patient having small bowel motility disorder as evidenced by delayed small bowel transit by 
wireless motility capsule (WMC) testing to > 6 hours. 
5. To participate in the study you will have to stop taking Octreotide (because it has the same 
mechanism of action as the study medication) if you are currently taking it, it should be 
stopped for at least 4 weeks before taking the first dose of this study medication.  
 
7.2 Exclusion Criteria 
 
General Exclusion Criteria 
• Age <18 or age >70 
• Pregnancy as assessed by urine pregnancy test. 
Exclusion Criteria for performing wireless motility capsule testing 
1. History of gastric bezoar 
2. History of Disorders of swallowing 
3. Known or suspected small bowel diverticula, diverticulitis, strictures, fistulas, Crohn’s 
disease, or any other relevant medical comorbidity (e.g. chronic alcohol abuse) 
4. Prior intestinal surgery, including IC valve resection or gastrointestinal surgeries that 
create a blind loop (e.g. Bilroth II or Roux-en-Y) 
5. History of Severe dysphagia to food or pills 
6. A participant who uses an implanted or portable electro-mechanical medical device such 
as a cardiac pacemaker or infusion pump 
7. Inability to be off intestinal transit altering medication for at least one week (e.g. opiates, 
laxatives, etc.) 
8. Any person unable or unwilling to undergo abdominal surgery. 
9. BMI > 40.  
Exclusion Criteria due to Lanreotide 
1. Current use or recent (within last 7 days) use of acid suppressive therapy, prokinetic 
agents, laxatives, and opiates, or other agents known to affect gastrointestinal motility. 
2. Disorders associated with presumed small intestinal motility disorders including: 
scleroderma, intestinal pseudo-obstruction, and autonomic visceral neuropathy (e.g. 
longstanding diabetes of more than 20 years and/or poorly controlled diabetes (glucose > 
250, glycosylated hemoglobin (HbA1c) > 8.5%) 
3. Current use of cyclosporine (Gengraf, Neoral, or Sandimmune), a medicine called 
bromocriptine (Parlodel, Cycloset), or medicines that lower your heart rate, such as beta 
blockers. 
4. Cardiac arrhythmia based on health history (palpitations, feeling a pause between 
heartbeats, lightheadedness, passing out, shortness of breath, or chest pain.  
Bradycardia and Tachycardia are monitored during every visit to the clinic, using pulse 


Page 17 of 42 
 
NCT NUMBER: - NCT03012594 
 
DATE: - OCTOBER 28TH, 2016 
 
This document is confidential and the property of the Northwell Health System.  No part of 
it may be transmitted, reproduced, published, or used by other persons without prior 
written authorization from the study sponsor. 
rate. 
ECG will be performed during screening visit and during 8th week of the study. The 
following are accessed with the ECG.  
 Bradycardia <60 beats/min. 
 Tachycardia >100 beats/min. 
 Atrial Fibrillation - Rapid irregular atrial signal with no real P-waves and 
irregular ventricular rate. 
 Ventricular Fibrillation - Irregular ventricular waveforms. 
 Sinus Arrhythmia - Normal beats, but triggered at an irregular interval 
from 60 to 100 BPM, causing varying R-R interval. 
 Missed beats. 
 
5. Chronic kidney disease(moderate and severe renal impairment as calculated by creatinine 
clearance of <50 mL/min) 
6. Hepatic Impairment – Subjects with Child-Pugh Class B and Class C.  
As assessed by  
Factor 
1 point 
2 points 
3 points 
Total bilirubin (μmol/L) 
<34 
34-50 
>50 
Serum albumin (g/L) 
>35 
28-35 
<28 
PT INR 
<1.7 
1.71-2.30 
>2.30 
Ascites 
None 
Mild 
Moderate to Severe 
Hepatic encephalopathy 
None 
Grade I-II (or 
suppressed with 
medication) 
Grade III-IV (or 
refractory) 


Page 18 of 42 
 
NCT NUMBER: - NCT03012594 
 
DATE: - OCTOBER 28TH, 2016 
 
This document is confidential and the property of the Northwell Health System.  No part of 
it may be transmitted, reproduced, published, or used by other persons without prior 
written authorization from the study sponsor. 
  
Child-Pugh 
classification 
Class A 
Class B 
Class C 
Total points 
5-6 
7-9 
10-15 
 
7. Significant electrolyte abnormalities: Anything outside of the normal range by +/- 20 % 
will be considered as abnormal. 
8. Cholilithiasis (Total bilirubin >2x of normal) 
9. Pancreatitis 
10. Hepatitis (AST, ALT or Alk Ph, greater than upper limit of normal(ULN), Serum albumin 
<3.0 g/dL unless prothrombin time is within the normal range) 
11. Present cholecystitis 
12. Uncontrolled congestive heart failure 
13. Known hypersensitivity to the study drug 
7.3 Vulnerable Populations 
 
Vulnerable populations will not be targeted for the purpose of the study. However some of the 
patients that we might see may belong to one or more of the above vulnerable population groups. 
 
7.4 Subject Recruitment and Screening 
The subjects will be recruited from the gastroenterology clinical practices at Northshore 
university hospital, Long island Jewish medical center and Lenox hill hospital. Patients referred 
to these hospitals will also be approached for recruitment. Potential subjects will be identified 
from their medical history.  If a subject shows interest in participation, then the study will be 
explained in a private room and medical history collected after the subject signs the consent 
form.  
The following information will be collected. 
• Age and gender 
• Race and ethnicity 
• Height and weight 


Page 19 of 42 
 
NCT NUMBER: - NCT03012594 
 
DATE: - OCTOBER 28TH, 2016 
 
This document is confidential and the property of the Northwell Health System.  No part of 
it may be transmitted, reproduced, published, or used by other persons without prior 
written authorization from the study sponsor. 
• Review of symptoms 
• Medical history 
• Medication history 
• Past blood test history and results  
• Past gastroenterological tests/ procedures history and findings 
• Past surgical history 
• Family history 
• Social history 
• Vitals 
• Questionnaire 
If the subject qualifies based on the above history and vitals then the following tests will be 
performed to look at eligibility. 
• Blood Glucose 
• ECG 
• Urine pregnancy test [Only in reproductive age group women with ability to conceive(no 
Hysterectomy, tubal ligation etc)] 
If the subject qualifies based on all the above then the following tests will be performed to look 
at eligibility. 
• Wireless motility capsule 
• Hydrogen breath test 
If the subject qualifies based on all the above then the subject will be enrolled to get the study 
medication. 
Subjects will be numbered chronologically based on the order they sign the consent form.  
 
7.5 Consent Process 
Eligible patients may only be included in the study after providing written (witnessed, where 
required by law or regulation), IRB/IEC/REB-approved informed consent, or, if incapable of 
doing so, after such consent has been provided by a legally acceptable representative of the 
patient. In cases where the patient’s representative gives consent, the patient should be informed 
about the study to the extent possible given his/her understanding. If the patient is capable of 
doing so, he/she should indicate assent by personally signing and dating the written informed 
consent document or a separate assent form. Informed consent must be obtained before 
conducting any study-specific procedures (i.e. all of the procedures described in the protocol). 


Page 20 of 42 
 
NCT NUMBER: - NCT03012594 
 
DATE: - OCTOBER 28TH, 2016 
 
This document is confidential and the property of the Northwell Health System.  No part of 
it may be transmitted, reproduced, published, or used by other persons without prior 
written authorization from the study sponsor. 
The process of obtaining informed consent should be documented in the patient source 
documents.  
Women of child bearing potential should be informed that taking the study medication may 
involve unknown risks to the fetus if pregnancy were to occur during the study and agree that in 
order to participate in the study they must adhere to the contraception requirement for the 
duration of the study. If there is any question that the patient will not reliably comply, they 
should not be entered in the study. 
 
• One of the study team members approved by the IRB will be obtaining the consent from 
the potential subjects. 
• Consent will be obtained in a private room(Eg;- Clinic room) 
• After explaining the study the subject will be given some time to think about the study 
and participation and once they are ready will be asked to sign the consent form. If they 
request more time, they will be sent home with a copy of the consent form to go over and 
will be approached later for completing the consent process if they are interested. 
• All subjects will be questioned about some of the critical points in the study and their 
understanding of the study will be accessed based on their responses. A questionnaire 
will be used to assess their understanding of the study. 
• An IRB approved consent form will be used in the study. 
 
 
We might have non English speaking subjects in the study. Phone translational services of the 
hospital will be used while explaining the study to these patients. The consent forms will not be 
translated in to any other language.   
 
7.6 Early Withdrawal of Subjects 
7.6.1 When and How to Withdraw Subjects 
 
• If the PI feels that continuing the subject in the study is going to be detrimental to the 
subject’s health then the subject will be informed and withdrawn from the study.  
• If the subject fails to adhere to the protocol requirements then they will be notified and 
even after informing if the subject fails to comply with the protocol requirements then the 
subject will be withdrawn from the study. 
• Other safety conditions for subject withdrawal based on safety end points. 
 
- Cardiac Function  (Bradycardia (Decreased heart rate) and hypertension) - If the subjects 
heart rate decreases by more than 20%, and either systolic or diastolic pressures increase 
by more than 20% during any of the visits when compared to that of the screening visit, 


Page 21 of 42 
 
NCT NUMBER: - NCT03012594 
 
DATE: - OCTOBER 28TH, 2016 
 
This document is confidential and the property of the Northwell Health System.  No part of 
it may be transmitted, reproduced, published, or used by other persons without prior 
written authorization from the study sponsor. 
and if the subject is on any other cardiac medication that might have caused this, then the 
subject will be referred to cardiologist for consultation and dose adjustment. If the change 
occurred without any concomitant medication then the subject will be removed from the 
study and will be monitored and treated as per standard of care. 
 
- Cholilithiasis (Gallstones)- Symptoms include severe right upper quadrant abdominal 
pain , nausea and vomiting, abdominal tenderness, clay colored stools, Jaundice 
(yellowing of skin and whites of the eye). If this occurs and has been confirmed (with 
Gallbladder echography), then the subjects will be removed from the study and will be 
monitored and treated as per standard of care.   
 
- Glucose Metabolism - (Hyperglycemia or hypoglycemia) – Blood glucose will be 
monitored during every visit. If there is a variation of more than 20% and if the subject is 
on any other diabetic medication that might have caused this, then the subject will be 
referred to her endocrinologist for dose adjustment. If the change occurred without any 
concomitant medication and life style changes then the subject will be removed from the 
study and will be monitored and treated as per standard of care.   
 
- Acute anaphylactic reactions – If the subjects develops anaphylactic reaction then he/she 
will be removed from the study and will be monitored and treated as per standard of care.  
  
- Pancreatitis – It is characterized by Upper abdominal pain that radiates into the back; it 
may be aggravated by eating, especially foods high in fat, Swollen and tender abdomen, 
Nausea and vomiting, Fever and Increased heart rate. Signs of pancreatitis will be 
checked for during every visit. If pancreatitis is confirmed then the subjects will be 
removed from the study and will be monitored and treated as per standard of care.  
  
- Hepatitis – Signs of hepatitis include Loss of appetite, Nausea and vomiting, Diarrhea, 
Dark-colored urine and pale bowel movements, Stomach pain and Jaundice (yellowing of 
skin and eyes). Signs of hepatitis will be checked for during every visit. If hepatitis is 
confirmed then the subjects will be removed from the study and will be monitored and 
treated as per standard of care.  
 
- Thyroid Function Abnormalities - If there is a variation of more than 20% from the 
screening visit values of T3, T4, TSH and if the subject is on any other thyroid 
medication that might have caused this, then the subject will be referred to her 
endocrinologist for dose adjustment. If the change occurred without any concomitant 
medication then the subject will be removed from the study and will be monitored and 
treated as per standard of care. 
 
 
7.6.2 Data Collection and Follow-up for Withdrawn Subjects 
 


Page 22 of 42 
 
NCT NUMBER: - NCT03012594 
 
DATE: - OCTOBER 28TH, 2016 
 
This document is confidential and the property of the Northwell Health System.  No part of 
it may be transmitted, reproduced, published, or used by other persons without prior 
written authorization from the study sponsor. 
• After withdrawal from the study, effort will be made to collect at least survival data from 
the subjects for the rest of the duration of the study. At least two modes of 
communication (email, phone etc) will be used to try to contact subjects who are lost to 
follow-up to get the survival data. 
8 Study Drug/Device  
8.1 Description 
 
SOMATULINE® DEPOT (lanreotide) INJECTION 
Initial U.S. Approval: 2007 
• It comes as a single use pre filled syringe. 
 
8.2 Treatment Regimen 
 
• Recommended dose is 120mg. 
• Subcutaneous injection. 
• Location of injection - Superior external quadrant of the buttock. Injection site should be 
alternated with subsequent injections. 
• The total duration of the study is 12 weeks from the first drug administration.  
• The last drug administration is on week 8 from the first drug administration.(Total of 3 
administrations 4 weeks apart) 
• All participants will be taken off of the study medication at the study completion. 
 
8.3 Method for Assigning Subjects to Treatment Groups 
Not applicable as everyone who qualifies and willing to participate will be given treatment. 
 
8.4 Preparation and Administration of Study Drug/Implantation of 
Study Device 
There is no preparation required for the drug. The medication comes in pre-filled syringes.  
After consenting and if the subject qualifies, study drug will be administered subcutaneously in 
the superior external quadrant of the buttock. This will be performed in a private room under the 
guidance of the research staff (eg: Clinic room). The injections will be administered by the 
licensed qualified staff. 
 


Page 23 of 42 
 
NCT NUMBER: - NCT03012594 
 
DATE: - OCTOBER 28TH, 2016 
 
This document is confidential and the property of the Northwell Health System.  No part of 
it may be transmitted, reproduced, published, or used by other persons without prior 
written authorization from the study sponsor. 
8.5 Subject Compliance Monitoring 
 
The medication is a subcutaneous injectable and will be performed in the clinic under the 
guidance of the research staff. The subjects will be sent a reminder before each of their 
appointments. The injections will be performed by the licensed qualified staff. 
 
8.6 Prior and Concomitant Therapy 
 
All prior and current medications history will be collected. 
 
The limited published data available indicate that somatostatin analogues may decrease the 
metabolic clearance of compounds known to be metabolised by cytochrome P450 enzymes, 
which may be due to the suppression of growth hormone. Since it cannot be excluded that 
lanreotide may have this effect, other drugs mainly metabolised by CYP3A4 and which have a 
low therapeutic index (e.g., quinidine, terfenadine) should therefore be used with caution.  
 
Cyclosporine bioavailability may be reduced.  
 
Drug interactions observed for octreotide, such as increased bromocriptine bioavailability, 
should be considered as possible drug interactions for lanreotide.  
 
In clinical studies of acromegalic patients with diabetes, lanreotide treatment generally resulted 
in improved glucose tolerance. However, blood glucose levels should be monitored at the start of 
lanreotide treatment or when the dose is altered, and anti-diabetic treatment should be adjusted 
accordingly.  
 
Due to a potential additive effect of bradycardia inducing drugs, such as beta-blockers with 
lanreotide, care should be taken when initiating lanreotide treatment. 
Prohibited concomitant medications for the entire duration of the study 
• Quinidine,  
• Terfenadine 
• Cyclosporine bioavailability may be reduced (Gengraf, Neoral, or Sandimmune) 
Prohibited concomitant medications for at least 1 week prior to Motility testing with 
wireless motility capsule, or Hydrogen breath testing. 
• Prokinetic agents  
o Bethanechol 
o Cisapride 
o Metaclopromide(Reglan®, Maxeran®) 
o Selective serotonin re-uptake inhibitors (SSRI’s) (Paroxetine, Fluoxetine) 


Page 24 of 42 
 
NCT NUMBER: - NCT03012594 
 
DATE: - OCTOBER 28TH, 2016 
 
This document is confidential and the property of the Northwell Health System.  No part of 
it may be transmitted, reproduced, published, or used by other persons without prior 
written authorization from the study sponsor. 
• Laxatives 
• Opiates 
Prohibited concomitant medications for at least 3 weeks prior to Hydrogen breath testing. 
• Oral Antibiotics 
Concomitant medications that may need dose adjustment due to possible effect on 
concomitant drug metabolism 
• Codeine (Codiene clearance decreased, hence dose should be decreased) 
• Bromocriptine (Parlodel, Cycloset) (Increases bioavailablity of Bromocrioptine) 
• Non Selective Beta Blockers 
o Propranolol 
o Bucindolol 
o Carteolol 
o Carvedilol 
o Labetalol 
o Nadolol 
o Oxprenolol 
o Pindolol 
o Sotalol 
o Timolol 
o Eucommia bark 
 
• Acid suppressive therapy 
o H2 Receptor blockers Cimetidine (Tagamet), Famotidine (Pepcid), Nizatidine 
(Axid) and Ranitidine (Zantac)) 
o Proton Pump Inhibitors ((Nexium), Lansoprazole (Prevacid), Omeprazole 
(Prilosec, Zegerid), Pantoprazole (Protonix), Rabeprazole (Aciphex) and 
Dexlansoprazole (Dexilant) 
• Antibiotics 
Concomitant medications that can be taken any time during the study. 
• Probiotics 
 
8.7 Packaging 
 
Lanreotide Autogel and lanreotide PRF are contained in a polypropylene syringe fitted with a 
stainless steel needle covered by a sheath. Each filled syringe is then inserted into a laminated 
pouch which is heat sealed. 
The lanreotide Autogel syringe includes, in addition, an automatic sharp needle protection 
system. 
 


Page 25 of 42 
 
NCT NUMBER: - NCT03012594 
 
DATE: - OCTOBER 28TH, 2016 
 
This document is confidential and the property of the Northwell Health System.  No part of 
it may be transmitted, reproduced, published, or used by other persons without prior 
written authorization from the study sponsor. 
The drug will be shipped in boxes of 6 syringes. 
 
 
8.8 Blinding of Study Drug/Device 
 
Not Applicable. 
 
8.9 Receiving, Storage, Dispensing and Return 
8.9.1 Receipt of Drug Supplies/Device 
 
The drug will be shipped from the sponsor to the Lenox Hill pharmacy, NSUH Research 
pharmacy and LIJ Pharmacy. 
 
Procurement  
 
• Supplier  -Ipsen Pharmaceuticals 
• Staff responsible for ordering drug(s) – Research Coordinator 
• Drug ordering method and form – Through email to the sponsor. 
 
Accountability 
Upon receipt of the of the study treatment supplies, an inventory will be performed and a 
drug receipt log filled out and signed by the person accepting the shipment.  The designated 
study staff at Lenox hills, NSUH research pharmacy or LIJ Pharmacy counts and verifies 
that the shipment contains all the items noted in the shipment inventory. Any damaged or 
unusable study drug in a given shipment (active drug or comparator) will be documented in 
the study files. The investigator will notify study sponsor of any damaged or unusable 
study treatments that were supplied to the investigator’s site. 
 
Treatment Schedule 
• Treatment arms and assigned doses including dose calculation - This is unblinded 
study and every qualifying subject will receive the medication. There is no dose 
calculation; the medication comes in prefilled 120mg syringes. 
 
• Dose schedules (e.g., loading, maintenance and tapering doses) - Each qualified 
subject will receive the medication 3 times (once per month). 
 
• Criteria for any dose modifications (i.e., dose escalation and/or reduction) – There 
is no dose modification 
 


Page 26 of 42 
 
NCT NUMBER: - NCT03012594 
 
DATE: - OCTOBER 28TH, 2016 
 
This document is confidential and the property of the Northwell Health System.  No part of 
it may be transmitted, reproduced, published, or used by other persons without prior 
written authorization from the study sponsor. 
Dose Preparation 
 
• Time frame for a drug request – The drug will be requested by a prescription from 
the physician emailed to the pharmacist at least 1 day before the actual treatment 
date. 
 
• The medication comes in prefilled 120mg syringes. 
 
 
8.9.2 Storage 
 
Study drug will be stored at research facility or research pharmacy at Lenox Hill pharmacy, 
NSUH Research pharmacy and LIJ Pharmacy in a secured area, under recommended 
temperature monitored storage conditions (between +2°C and +8°C). 
 
8.9.3 Dispensing of Study Drug/Device 
 
This is non-Randomized study and every subject who signs the consent form and qualifies 
will get the study medication. Regular study drug/device reconciliation will be performed 
to document drug assigned; drug consumed, and drug remaining.  This reconciliation will 
be logged on the drug/ reconciliation form, and signed and dated by Lenox Hill pharmacy, 
NSUH Research pharmacy and LIJ Pharmacy. 
 
Pick-up or Delivery 
The drug will be picked up from pharmacy by study coordinators and delivered to 
locations. The drug will be picked up and kept on ice/cold pack in an ice box and then 
taken to the location of the drug administration. The drug will be administered either at 
LIJMC, Lenox hill, 600 northern blvd drive or NSUH (drug collected from NSUH 
Pharmacy). We expect majority of the drug to be administered at Lenox hill or LIJMC, the 
other sites are for back up, just in case if patients does not want to or cannot travel for the 
medication. While transporting the medication from NSUH to 600 Northern blvd, the study 
staff will collect the medication from the NSUH pharmacy, place it in a Ziploc bag, seal it 
and place the bag on ice/cold pack in an ice box and deliver it to 600 northern blvd. The 
usual expected travel time from NSUH to 600 Northern blvd is 5-10 minutes. Upon 
reaching the destination the medication and the ice/cold pack will be checked to see if 
everything is in place, that the ice has not melted completely/cold pack has not reached the 
room temperature and that there is no damage to the medication (change in color, turbidity, 
and breakage). If any of the above occurs then that medication will not be used and a new 
medication will be brought from NSUH. 


Page 27 of 42 
 
NCT NUMBER: - NCT03012594 
 
DATE: - OCTOBER 28TH, 2016 
 
This document is confidential and the property of the Northwell Health System.  No part of 
it may be transmitted, reproduced, published, or used by other persons without prior 
written authorization from the study sponsor. 
 
Administration 
 
• Location of injection – Sub-cutaneously in superior external quadrant of the 
buttock. Injection site should be alternated with subsequent injections. 
• The injections will be administered by the licensed qualified staff. 
 
Drug Retrieval 
• All the drugs are administered at the site by the qualified personnel. Drug is not 
given to the patient to take home for self administration. 
 
 
 
8.9.4 Return or Destruction of Study Drug/Device 
 
At the completion of the study, there will be a final reconciliation of drug shipped, drug 
consumed, and drug remaining. This reconciliation will be logged on the drug 
reconciliation form, signed and dated.  Any discrepancies noted will be investigated, 
resolved, and documented prior to return or destruction of unused study drug.  Drug 
destroyed on site will be documented in the study files. 
 
9 Study Procedures 
 
LIST OF STUDY PROCEDURES 
 
Consent 
 
Medical and Medication History 
 
Inclusion Exclusion Criteria 
 
Height and weight 
 
Physical exam 
 
Vitals - Heart rate, Blood Pressure, Respiratory rate and SPO2 
 
ECG - ECG will be used to screen patients for cardiac arrhythmia, especially any QT 
prolongation that might be present. 
 
Questionnaire - PAGI-SYM: This questionnaire is a validated symptom scale, which asks about 


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it may be transmitted, reproduced, published, or used by other persons without prior 
written authorization from the study sponsor. 
the severity of symptoms related to gastrointestinal problem. 
 
Pregnancy test (In Women of reproductive age group) 
 
Wireless capsule testing (During Screening performed if it is not performed as a standard of 
care in the last 2 months. During Week 12 they are being performed as part of the study) - The 
SmartPill wireless motility device will be used to gather data. SmartPill is an ingestible capsule 
utilizing sensor technology to evaluate GI motility. It can senses and record pH, pressure and 
temperature data from within the entire GI tract, which are transmitted wirelessly to the 
SmartPill data recorder. It is superior to existing diagnostic tests for elimination of radiation 
exposure, minimized patient downtime, and comfort and easiness of the procedure. This device 
is already FDA approved and has been in use for the evaluation of suspected gastroparesis and 
chronic constipation since 2007. 
 
Hydrogen breath testing (During Screening performed if it is not performed as a standard 
of care in the last 2 months. During Week 6 and Week 12 they are being performed as part 
of the study) - The hydrogen breath test is a test that uses the measurement of hydrogen in the 
breath to diagnose several conditions that cause gastrointestinal symptoms. In humans, only 
bacteria - specifically, anaerobic bacteria in the colon - are capable of producing hydrogen. The 
bacteria produce hydrogen when they are exposed to unabsorbed food, particularly sugars and 
carbohydrates, but not proteins or fats. Although limited hydrogen is produced from the small 
amounts of unabsorbed food that normally reach the colon, large amounts of hydrogen may be 
produced when there is a problem with the digestion or absorption of food in the small intestine, 
that allows more unabsorbed food to reach the colon. 
Large amounts of hydrogen also may be produced when the colon bacteria move back into the 
small intestine, a condition called bacterial overgrowth of the small bowel. In this latter instance, 
the bacteria are exposed to unabsorbed food that has not yet had a chance to completely traverse 
the small intestine to be fully digested and absorbed. Some of the hydrogen produced by the 
bacteria, whether in the small intestine or the colon, is absorbed into the blood flowing through 
the wall of the small intestine and colon. The hydrogen-containing blood travels to the lungs 
where the hydrogen is released and exhaled in the breath where it can be measured.  
 
STUDY LAB TESTS 
1. Blood Glucose 
2. CBC + HbA1c 
3. Cardiac Panel 
4. Hepatic function panel 
5. Renal Function Panel 
6. Thyroid Function Tests 
7. Urinalysis (dipstick) 
 


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it may be transmitted, reproduced, published, or used by other persons without prior 
written authorization from the study sponsor. 
9.1 Visit 1 (Screening) 
 
The following tests/procedures will be performed during this visit 
• Consent 
• Medical and Medication History 
• Inclusion and Exclusion Criteria 
• Vitals 
• Complete Physical examination 
• ECG 
• Questionnaire 
• Blood Glucose 
• Lab evaluations (CBC + HbA1c, Cardiac Panel, Hepatic function panel, Renal Function 
Panel, and Thyroid Function Tests) 
• Urine Pregnancy test 
 
9.2 Visit 2 (-15 Days (±7 days)) 
• Wireless motility capsule testing - Performed only if the subject did not have a clinically 
indicated testing within the last 2  months as standard of care 
• Hydrogen breath test - Performed only if the subject did not have a clinically indicated 
testing within the last 2  months as standard of care 
If both of these tests are already performed within the last 2 months as per standard of care and 
the subject can provide the report then they will not be repeated during this visit, and this visit is 
not required. 
 
9.3 Visit 3 (Day0 (±7 days)) 
• Short Physical exam 
• Medication History 
• Vitals 
• Questionnaire 
• Blood Glucose 
• Pregnancy test 
& Study drug administration and patient monitoring for at least 30 minutes after drug 
administration 
 
9.4 Visit 4 (Week 2 (±7 days)) 
• Medication History 
• Vitals 
• Blood Glucose 
• Adverse event assessment 


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it may be transmitted, reproduced, published, or used by other persons without prior 
written authorization from the study sponsor. 
• Questionnaire 
 
9.5 Visit 5 (Week 4 (±7 days)) 
• Short Physical exam 
• Medication History 
• Vitals 
• Questionnaire 
• Blood Glucose 
• Lab evaluations(CBC + HbA1c, Cardiac Panel, Hepatic function panel, Renal Function 
Panel, and Thyroid Function Tests) 
• Pregnancy test 
& Study drug administration and patient monitoring for at least 30 minutes after drug 
administration 
 
9.6 Visit 6 (Week 6 (±7 days)) 
• Medication History 
• Vitals 
• Blood Glucose 
• Adverse event assessment 
• Questionnaire 
• Hydrogen breath test 
 
9.7 Visit 7 (Week 8 (±7 days)) 
• Short Physical exam 
• Medication History 
• Blood Glucose 
• ECG 
• Vitals 
• Adverse event assessment 
• Questionnaire 
• Pregnancy test 
 
& Study drug administration and patient monitoring for at least 30 minutes after drug 
administration 
9.8 Visit 8 (Week 12 (±7 days)) 
• Medication History 
• Vitals 


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it may be transmitted, reproduced, published, or used by other persons without prior 
written authorization from the study sponsor. 
• Adverse event assessment 
• Questionnaire 
• Urine analysis 
• Lab evaluations (CBC + HbA1c, Cardiac Panel, Hepatic function panel, Renal Function 
Panel, and Thyroid Function Tests) 
• Hydrogen Breath testing 
• Wireless motility capsule testing 
 
 Risks to Subjects 
Known side effects of lanreotide. 
mild to moderate pain, itching or lump at the injection  
Very Common (more than 10% of patients) 
Diarrhea, 
Abdominal pain, 
Nausea, 
Dizziness 
 
Fairly common  
Bradycardia (Mean heart rate decreased by 4 beats per minute in 7.1% of 
acromegalic patients) 
Cholilithiasis (With double the suggested dose, gall stones were observed in 
12.5% of normal control patients) 
Known side effects of Octreotide. 
 
Most frequent adverse effects (more than 10% of patients) 
 
 
Headache, 
Hypothyroidism,  
Cardiac conduction changes,  
Gastrointestinal reactions (including cramps, nausea/vomiting and diarrhoea or 
constipation),  
Gallstones,  
Reduction of insulin release,  
Hyperglycemia  
Symptoms include Increased thirst, Headaches, Trouble concentrating, Blurred 


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it may be transmitted, reproduced, published, or used by other persons without prior 
written authorization from the study sponsor. 
vision, Frequent peeing, Fatigue (weak, tired feeling), Weight loss. 
Hypoglycemia 
Symptoms include Shakiness, Nervousness or anxiety, Sweating, chills and 
clamminess, Irritability or impatience, Confusion, including delirium, Rapid/fast 
heartbeat, Lightheadedness or dizziness, Hunger and nausea, Sleepiness, 
Blurred/impaired vision, Tingling or numbness in the lips or tongue, Headaches, 
Weakness or fatigue, Anger, stubbornness, or sadness, Lack of coordination, Nightmares 
or crying out during sleep and Seizures. Subjects will be advised to carry with them at all 
times hard candies, jellybeans, or gumdrops and consume them if any of the above 
symptoms occur. 
Transient injection site reactions 
 
Adverse effects (more than 1%) 
 
 
Slow heart rate,  
Skin reactions such as pruritus,  
Hyperbilirubinemia,  
Dizziness and  
Dyspnoea 
Rare side effects include  
Acute anaphylactic reactions,  
Pancreatitis and  
Hepatitis. 
One study reported a possible association with rheumatoid arthritis, some studies reported 
alopecia, Rats which were treated by octreotide experienced erectile dysfunction. 
 
During every visit after the initiation of the treatment the subjects will be assessed for any 
of these side effects.  
 
10 Potential Benefit to Subjects 
The potential benefit for the subject is the decreased frequency of administration, compared to 
the current treatment and hence increased compliance and better control of the disease. 
 
11 Research Related Harm/Injury 
 
All the three hospitals participating in this study are tertiary care centers with the ability to 


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it may be transmitted, reproduced, published, or used by other persons without prior 
written authorization from the study sponsor. 
diagnose and treat various medical conditions. If a complication arises, then subjects will be 
withdrawn from the study and appropriate care will be given as per standard of care.  
 
The expenses of the research related harm/injury will be covered either by the research 
participant or their insurance company. 
 
 
12 Provisions to Protect Privacy Interests of Subjects 
 
Potential subjects will be identified from their medical records and the investigators practice by 
the investigators or the study team. Other physicians in the department will be notified about the 
study and refer their patients if they fell that the patient might benefit from participating in the 
study. All the discussions with the patient will be performed in a private room by the research 
staff. All email communication with the subjects will be through secure Northwell health system 
email server. 
 
13 Statistical Plan 
13.1 Sample Size Determination 
This is a pilot study and there is no preliminary data available to calculate the sample size for this 
study. 
 
13.2 Statistical Methods 
Summary statistics (mean, SD, frequencies, and percentages) will be presented for demographic 
variables.  
 
Wireless motility capsule parameters such as Small bowel transit time, gastric transit time, 
colonic transit time, whole gut transit time, contractions/minute, amplitude, and motility index 
will be compared pre and post intervention using paired Student’s t-test. When the variables are 
extremely skewed (i.e. when the required assumption of normality of the paired differences is 
violated), the appropriate nonparametric test, Wilcoxon signed rank test, will be used instead, 
and medians will be reported. 
 
Hydrogen breath test parameters such as hydrogen concentration (ppm) and Methane 
concentration (ppm) in the breath will be compared for pre and post intervention using repeated 
measures ANOVA to determine if there is any change in the bacterial overgrowth after 
intervention. If the standard model assumptions are not met then data transformations will be 
explored. 
 
PAGI-SYM Questionnaire – This questionnaire uses a 6-point Likert scale, ranging from 0 


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it may be transmitted, reproduced, published, or used by other persons without prior 
written authorization from the study sponsor. 
(none/absent) to 5 (very severe) for various gastrointestinal symptoms. 20 items and 6  subscales 
covering heartburn/regurgitation (7 items), nausea/vomiting (3 items), post-prandial 
fullness/early satiety (4 items), bloating (2 items), upper abdominal pain (2 items), and lower 
abdominal pain (2 items). Mean of the items in each subscale will be compared pre and post 
intervention using repeated measures ANOVA. If the standard model assumptions are not met 
then data transformations will be explored. The half-scale rule will be applied for missing data 
(i.e., the subscale score is calculated using the mean of non-missing items; when more than 50% 
of items are missing, the score will be set to missing). The total score is calculated by taking the 
mean of the subscales. If a subscale score is missing, the PAGI-SYM total score will be set to 
missing. 
 
Based on the limited sample size, instead of performing regression analysis, sub-group analysis 
will be applied by age, gender or any confounding variables. 
 
13.3 Subject Population(s) for Analysis 
 
Not Applicable 
 
14 Safety and Adverse Events 
14.1 Definitions 
Adverse Event 
An adverse event (AE) is any symptom, sign, illness or experience that develops or 
worsens in severity during the course of the study.  Intercurrent illnesses or injuries should 
be regarded as adverse events.  Abnormal results of diagnostic procedures are considered to 
be adverse events if the abnormality: 
• results in study withdrawal 
• is associated with a serious adverse event 
• is associated with clinical signs or symptoms 
• leads to additional treatment or to further diagnostic tests 
• is considered by the investigator to be of clinical significance 
Serious Adverse Event 
Adverse events are classified as serious or non-serious.  A serious adverse event is any AE 
that is:  
• fatal 
• life-threatening 
• requires or prolongs hospital stay 
• results in persistent or significant disability or incapacity 
• a congenital anomaly or birth defect 
• an important medical event 


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This document is confidential and the property of the Northwell Health System.  No part of 
it may be transmitted, reproduced, published, or used by other persons without prior 
written authorization from the study sponsor. 
 
Important medical events are those that may not be immediately life threatening, but are 
clearly of major clinical significance.   They may jeopardize the subject, and may require 
intervention to prevent one of the other serious outcomes noted above.  For example, drug 
overdose or abuse, a seizure that did not result in in-patient hospitalization, or intensive 
treatment of bronchospasm in an emergency department would typically be considered 
serious.  
 
All adverse events that do not meet any of the criteria for serious should be regarded as 
non-serious adverse events.  
Adverse Event Reporting Period 
The study period during which adverse events must be reported is normally defined as the 
period from the initiation of any study procedures to the end of the study treatment follow-
up.  For this study, the study treatment follow-up is defined as 30 days following the last 
administration of study treatment.  
Preexisting Condition 
A preexisting condition is one that is present at the start of the study.  A preexisting 
condition should be recorded as an adverse event if the frequency, intensity, or the 
character of the condition worsens during the study period. 
General Physical Examination Findings 
At screening, any clinically significant abnormality should be recorded as a preexisting 
condition.  At the end of the study, any new clinically significant findings/abnormalities 
that meet the definition of an adverse event must also be recorded and documented as an 
adverse event.  
Post-study Adverse Event 
All unresolved adverse events should be followed by the investigator until the events are 
resolved, the subject is lost to follow-up, or the adverse event is otherwise explained.  At 
the last scheduled visit, the investigator should instruct each subject to report any 
subsequent event(s) that the subject, or the subject’s personal physician, believes might 
reasonably be related to participation in this study.  The investigator should notify the study 
sponsor of any death or adverse event occurring at any time after a subject has discontinued 
or terminated study participation that may reasonably be related to this study.  The sponsor 
should also be notified if the investigator should become aware of the development of 
cancer or of a congenital anomaly in a subsequently conceived offspring of a subject that 
has participated in this study.  
Abnormal Laboratory Values 
A clinical laboratory abnormality should be documented as an adverse event if any one of 
the following conditions is met:  
• The laboratory abnormality is not otherwise refuted by a repeat test to confirm the 
abnormality 
• The abnormality suggests a disease and/or organ toxicity 


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it may be transmitted, reproduced, published, or used by other persons without prior 
written authorization from the study sponsor. 
• The abnormality is of a degree that requires active management; e.g. change of 
dose, discontinuation of the drug, more frequent follow-up assessments, further 
diagnostic investigation, etc. 
Hospitalization, Prolonged Hospitalization or Surgery 
Any adverse event that results in hospitalization or prolonged hospitalization should be 
documented and reported as a serious adverse event unless specifically instructed otherwise 
in this protocol.  Any condition responsible for surgery should be documented as an 
adverse event if the condition meets the criteria for and adverse event.  
 
Neither the condition, hospitalization, prolonged hospitalization, nor surgery are reported 
as an adverse event in the following circumstances: 
• Hospitalization or prolonged hospitalization for diagnostic or elective surgical 
procedures for a preexisting condition.  Surgery should not be reported as an 
outcome of an adverse event if the purpose of the surgery was elective or diagnostic 
and the outcome was uneventful. 
• Hospitalization or prolonged hospitalization required to allow efficacy 
measurement for the study. 
• Hospitalization or prolonged hospitalization for therapy of the target disease of the 
study, unless it is a worsening or increase in frequency of hospital admissions as 
judged by the clinical investigator. 
14.2 Recording of Adverse Events 
 At each contact with the subject, the investigator must seek information on adverse events by 
specific questioning and, as appropriate, by examination.  Information on all adverse events 
should be recorded immediately in the source document, and also in the appropriate adverse 
event module of the case report form (CRF).  All clearly related signs, symptoms, and abnormal 
diagnostic procedures results should recorded in the source document, though should be grouped 
under one diagnosis. 
 
All adverse events occurring during the study period must be recorded.  The clinical course of 
each event should be followed until resolution, stabilization, or until it has been determined that 
the study treatment or participation is not the cause.  Serious adverse events that are still ongoing 
at the end of the study period must be followed up to determine the final outcome.  Any serious 
adverse event that occurs after the study period and is considered to be possibly related to the 
study treatment or study participation should be recorded and reported immediately. 
14.3 Reporting of Serious Adverse Events 
14.3.1 
EC/IRB Notification by Investigator 
Reports of all serious adverse events (including follow-up information) must be 
submitted to the EC/IRB according to their policies.  Copies of each report and 


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it may be transmitted, reproduced, published, or used by other persons without prior 
written authorization from the study sponsor. 
documentation of EC/IRB notification and receipt will be kept in the Clinical 
Investigator’s binder. 
14.3.2 
FDA Notification by Sponsor 
The study sponsor shall notify the FDA by telephone or by facsimile transmission of any 
unexpected fatal or life-threatening experience associated with the use of the drug as soon 
as possible but no later than 7 calendar days from the sponsor’s original receipt of the 
information. 
 
If a previous adverse event that was not initially deemed reportable is later found to fit 
the criteria for reporting, the study sponsor will submit the adverse event in a written 
report to the FDA as soon as possible, but no later than 15 calendar days from the time 
the determination is made. 
14.4 Unblinding Procedures 
 
Not applicable as this is not a blinded study. 
 
 
14.5 Stopping Rules  
 
Study drug must be discontinued and the patient withdrawn from the trial if the investigator 
determines that continuing it would result in a significant safety risk for that patient.  
The following circumstances require study drug discontinuation: 
Please look at early withdrawal of subjects section. 
 
 
14.6  Medical Monitoring 
It is the responsibility of the Principal Investigator to oversee the safety of the study at his/her 
site.  This safety monitoring will include careful assessment and appropriate reporting of adverse 
events as noted above, as well as the construction and implementation of a site data and safety-
monitoring plan (see section 17 Auditing, Monitoring and Inspecting).  Medical monitoring will 
include a regular assessment of the number and type of serious adverse events. 
14.7  Data and Safety Monitoring  
14.7.1 
Data and Safety Monitoring Plan 
 
The Dr. Miller is responsible for evaluating and monitoring the data. Data will be assessed after 


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This document is confidential and the property of the Northwell Health System.  No part of 
it may be transmitted, reproduced, published, or used by other persons without prior 
written authorization from the study sponsor. 
every 10 patients that receive the investigational medication. 
 
Dr. Larry Miller 
Department of Medicine (Gastroenterology) 
Northwell health system 
270-05 76th Avenue, New Hyde park, NY. 11040 
Phone: 718-470-4691 
Fax: 516-562-2683 
lmiller7@northwell.edu 
The data that is being captured under the monitoring plan includes – Heart rate, Cholilithiasis, 
Blood glucose, Anaphylactic reactions, Pancreatitis, Hepatitis and thyroid function 
abnormalities. Serious adverse events will be reported within 24 hours to the data and safety 
monitor. Non-serious adverse events and non-serious unanticipated problems will be reported 
after every 10 patients. 
Please refer to the stopping rules in the section 7.6.1 titled when and how to withdraw subjects. 
 
 
15 Data Handling and Record Keeping 
15.1 Confidentiality 
Information about study subjects will be kept confidential and managed according to the 
requirements of the Health Insurance Portability and Accountability Act of 1996 (HIPAA).  
Those regulations require a signed subject authorization informing the subject of the following:  
• What protected health information (PHI) will be collected from subjects in this study 
• Who will have access to that information and why 
• Who will use or disclose that information 
• The rights of a research subject to revoke their authorization for use of their PHI.  
In the event that a subject revokes authorization to collect or use PHI, the investigator, by 
regulation, retains the ability to use all information collected prior to the revocation of subject 
authorization.  For subjects that have revoked authorization to collect or use PHI, attempts 
should be made to obtain permission to collect at least vital status (i.e. that the subject is alive) at 
the end of their scheduled study period. 
15.2 Source Documents 
Source data is all information, original records of clinical findings, observations, or other 
activities in a clinical trial necessary for the reconstruction and evaluation of the trial.  Source 
data are contained in source documents   Examples of these original documents, and data records 
include: hospital records, clinical and office charts, laboratory notes, memoranda, subjects’ 
diaries or evaluation checklists, pharmacy dispensing records, recorded data from automated 
instruments, copies or transcriptions certified after verification as being accurate and complete, 


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it may be transmitted, reproduced, published, or used by other persons without prior 
written authorization from the study sponsor. 
microfiches, photographic negatives, microfilm or magnetic media, x-rays, subject files, and 
records kept at the pharmacy, at the laboratories, and at medico-technical departments involved 
in the clinical trial. 
15.3 Case Report Forms 
The study case report form (CRF) is the primary data collection instrument for the study.  All 
data requested on the CRF must be recorded.  All missing data must be explained.  If a space on 
the CRF is left blank because the procedure was not done or the question was not asked, write 
“N/D”.  If the item is not applicable to the individual case, write “N/A”.  All entries should be 
printed legibly in black ink.  If any entry error has been made, to correct such an error, draw a 
single straight line through the incorrect entry and enter the correct data above it.  All such 
changes must be initialed and dated.  DO NOT ERASE OR WHITE OUT ERRORS.  For 
clarification of illegible or uncertain entries, print the clarification above the item, then initial and 
date it. 
15.4 Records Retention 
 
It is the investigator’s responsibility to retain study essential documents for at least 2 years after 
the last approval of a marketing application in their country and until there are no pending or 
contemplated marketing applications in their country or at least 2 years have elapsed since the 
formal discontinuation of clinical development of the investigational product.  These documents 
should be retained for a longer period if required by an agreement with the sponsor.  In such an 
instance, it is the responsibility of the sponsor to inform the investigator/institution as to when 
these documents no longer need to be retained.  
 
ClinicalTrials.gov Registration  
A description of this clinical trial will be available on http://www.Clinical Trials.gov , as 
required by U.S. Law. This Web site will not include information that can identify you. At most, 
the Web site will include a summary of the results. You can search this website at any time. 
 
16 Study Monitoring, Auditing, and Inspecting 
16.1 Study Monitoring Plan 
This study will be monitored according to the monitoring plan.  The investigator will allocate 
adequate time for such monitoring activities.  The Investigator will also ensure that the monitor 
or other compliance or quality assurance reviewer is given access to all the above noted study-
related documents and study related facilities (e.g. pharmacy, diagnostic laboratory, etc.), and 
has adequate space to conduct the monitoring visit. 
16.2 Auditing and Inspecting 
The investigator will permit study-related monitoring, audits, and inspections by the EC/IRB, the 
sponsor, government regulatory bodies, and University compliance and quality assurance groups 


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it may be transmitted, reproduced, published, or used by other persons without prior 
written authorization from the study sponsor. 
of all study related documents (e.g. source documents, regulatory documents, data collection 
instruments, study data etc.).  The investigator will ensure the capability for inspections of 
applicable study-related facilities (e.g. pharmacy, diagnostic laboratory, etc.). 
 
Participation as an investigator in this study implies acceptance of potential inspection by 
government regulatory authorities and applicable University compliance and quality assurance 
offices. 
17 Ethical Considerations 
This study is to be conducted according to US and international standards of Good Clinical 
Practice (FDA Title 21 part 312 and International Conference on Harmonization guidelines), 
applicable government regulations and Institutional research policies and procedures. 
 
This protocol and any amendments will be submitted to a properly constituted independent 
Ethics Committee (EC) or Institutional Review Board (IRB), in agreement with local legal 
prescriptions, for formal approval of the study conduct.  The decision of the EC/IRB concerning 
the conduct of the study will be made in writing to the investigator and a copy of this decision 
will be provided to the sponsor before commencement of this study.  The investigator should 
provide a list of EC/IRB members and their affiliate to the sponsor. 
 
All subjects for this study will be provided a consent form describing this study and providing 
sufficient information for subjects to make an informed decision about their participation in this 
study.  See Attachment ___ for a copy of the Subject Informed Consent Form.  This consent 
form will be submitted with the protocol for review and approval by the EC/IRB for the study.  
The formal consent of a subject, using the EC/IRB-approved consent form, must be obtained 
before that subject is submitted to any study procedure.  This consent form must be signed by the 
subject or legally acceptable surrogate, and the investigator-designated research professional 
obtaining the consent.  
 
18 Study Finances 
18.1 Funding Source 
 
This study is financed through a grant from Ipsen Biopharmaceuticals. There are no additional 
foreseeable costs to the subject due to his/her participation in the study, other than their normal 
standard of care costs. 
 
18.2 Conflict of Interest 
Any investigator who has a conflict of interest with this study (patent ownership, royalties, or 
financial gain greater than the minimum allowable by their institution, etc.) must have the 
conflict reviewed by a properly constituted Conflict of Interest Committee with a Committee-


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NCT NUMBER: - NCT03012594 
 
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This document is confidential and the property of the Northwell Health System.  No part of 
it may be transmitted, reproduced, published, or used by other persons without prior 
written authorization from the study sponsor. 
sanctioned conflict management plan that has been reviewed and approved by the study sponsor 
prior to participation in this study.  All North Shore-LIJ Health System investigators will follow 
the University conflict of interest policy. 
18.3 Subject Stipends or Payments 
Subjects will be paid $50 during each of their visits of Day 0, Weeks 2, 4, 6, 8, and 12 for total 
of $300.  
 
19 Publication Plan 
 
Neither the complete nor any part of the results of the study carried out under this protocol, nor 
any of the information provided by the sponsor for the purposes of performing the study, will be 
published or passed on to any third party without the consent of the study sponsor.  Any 
investigator involved with this study is obligated to provide the sponsor with complete test 
results and all data derived from the study. 
The results of the study might be published in scientific journals, abstracts and or conferences. 
However no personal information will be disclosed in these publications. 
20 References 
 
1. 
Soudah HC, Hasler WL, Owyang C. Effect of octreotide on intestinal motility and 
bacterial overgrowth in scleroderma. The New England journal of medicine. 1991;325(21):1461-
7. Epub 1991/11/21. doi: 10.1056/nejm199111213252102. PubMed PMID: 1944424. 
2. 
Owyang C. Octreotide in gastrointestinal motility disorders. Gut. 1994;35(3 Suppl):S11-
S4. PubMed PMID: PMC1374389. 
3. 
Edmunds MC, Chen JD, Soykan I, Lin Z, McCallum RW. Effect of octreotide on gastric 
and small bowel motility in patients with gastroparesis. Aliment Pharmacol Ther. 
1998;12(2):167-74. Epub 1998/08/06. PubMed PMID: 9692691. 
4. 
De Giorgio R, Sarnelli G, Corinaldesi R, Stanghellini V. Advances in our understanding 
of the pathology of chronic intestinal pseudo-obstruction. Gut. 2004;53(11):1549-52. doi: 
10.1136/gut.2004.043968. PubMed PMID: PMC1774265. 
5. 
Iida H, Ohkubo H, Inamori M, Nakajima A, Sato H. Epidemiology and Clinical 
Experience of Chronic Intestinal Pseudo-Obstruction in Japan: A Nationwide Epidemiologic 
Survey. Journal of Epidemiology. 2013;23(4):288-94. doi: 10.2188/jea.JE20120173. PubMed 
PMID: PMC3709546. 
6. 
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NCT NUMBER: - NCT03012594 
 
DATE: - OCTOBER 28TH, 2016 
 
This document is confidential and the property of the Northwell Health System.  No part of 
it may be transmitted, reproduced, published, or used by other persons without prior 
written authorization from the study sponsor. 
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