A Post-marketing Drug Intensive Monitoring Study of Compound Sodium Picosulfate Granules for Bowel Preparation in Chinese Population
Conditions: Bowel Cleansing
Sponsor: Ferring Pharmaceuticals

 
 
 
Cover page for Protocol 
 
Sponsor name 
Ferring Pharmaceuticals A/S 
NCT Number 
NCT04852120 
Sponsor trial ID:  
000373 
Official title of study 
A post-marketing drug intensive monitoring study 
of Compound Sodium Picosulfate Granules for 
bowel preparation in Chinese population 
Document Date 
25 November 2021 
 

Sodium Picosulfate + Magnesium Oxide + Citric AcidTrial Code: 000373
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NON-INTERVENTIONAL STUDY (NIS) PROTOCOL
A post-marketing drug intensive monitoring study of 
Compound Sodium Picosulfate Granules for bowel preparation in Chinese population
Trial Code: 000373
Medicinal Product:
Compound Sodium Picosulfate Granules
Indication:
-
To clean the bowel prior to X-ray examination or 
endoscopy
-
To clean the bowel prior to surgery when judged 
clinically necessary
Phase:
Post-marketing drug intensive monitoring
Name and Address of Sponsor:
Ferring Pharmaceuticals (China) Co., Ltd.
No.6, Hui Ling Lu (Ferring Road), National Health 
Technology Park 528437 Zhongshan City, Guangdong 
Province, People's Republic of China
The information in this document is confidential and is proprietary to Ferring Pharmaceuticals (China) Co., Ltd. or another 
company within the Ferring Group. It is understood that information in this document shall not be disclosed to any third 
party, in any form, without prior written consent of an authorised officer of Ferring Pharmaceuticals (China) Co., Ltd. or 
another company within the Ferring Group.

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SYNOPSIS
TITLE OF STUDY 
A post-marketing drug intensive monitoring study of Compound Sodium Picosulfate Granules for 
bowel preparation in Chinese population
SIGNATORY INVESTIGATOR(S)
Not applicable
STUDY SITE(S)
The study is planned to be carried out in 20 pharmacies and hospitals in Chinese mainland.
PLANNED STUDY PERIOD 
Apr 2021- Dec2022
OBJECTIVES
To monitor and assess the safety profile of Compound Sodium Picosulfate Granules in the real-
world clinical practice in Chinese population.
METHODOLOGY 
This is a post-marketing multi-site, prospective, non-interventional study. Compound Sodium 
Picosulfate granules or other similar drugs will be prescribed to the subject based on physicians’
clinical judgement. 
The study will collect all stipulated events reported from signing the informed consent form (ICF)
to about 37(+2) hours after first medication. Contacting the subject remotely by pharmacist or 
hospital staff will be used to collect adverse events/reactions and other relevant information. No 
additional tests or examinations will be performed on subjects, no drugs will be provided to the 
subjects.

The study staff will register the eligible subjects. The subjects will sign the informed 
consent, provide contact information. Demographic characteristics (gender, age, nation, 
height, weight) of subjects will be collected. 

Contact the subjects remotely 37(+2) hours after first medication to collect any adverse 
events and information on the Compound Sodium Picosulfate granules administration.
All adverse events collected will be sent to the sponsor for case processing.
NUMBER OF SUBJECTS
Sponsor will collect as many subjects' safety data as possible.
CRITERIA FOR INCLUSION / EXCLUSION
Inclusion criteria:

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
Agree to participate in this study and sign the ICF by subject or the legal representative.

Subjects taking the Compound Sodium Picosulfate Granules drug in real clinical practice.
Exclusion criteria:

Subjects who are enrolled in other on-going studies, which prohibit any participation in this 
non-interventional study.
MONITORING PRODUCT
Compound Sodium Picosulfate Granules
DURATION OF PARTICIPATION
The duration of participation for each subject will be from signing the ICF to about 37(+2) hours
after first medication. The sponsor will decide on the requirement for any follow-up of AEs 
persisting.
STATISTICAL METHODS
As this is a descriptive study, no formal statistical testing will be carried out.
Descriptive statistics on continuous data will include the counts, number of missing data, means, 
standard deviations, medians, minimum and maximum values, while categorical data will be 
summarized using frequency counts and percentages.
Adverse events (AE) will be coded according to the latest version of the MedDRA dictionary and 
presented in "preferred term (PT) and system organ class (SOC)". The incidence of each AE will 
be calculated.

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TABLE OF CONTENTS
1
INTRODUCTION................................................................................................................................9
1.1
Background................................................................................................................................9
1.2
Preliminary Safety Evaluation.................................................................................................10
1.2.1
Preclinical Safety Data...............................................................................................10
1.2.2
Clinical Safety Data ...................................................................................................11
1.2.3
Post-authorisation Experience ...................................................................................15
1.3
Study Rationale .......................................................................................................................15
2
STUDY OBJECTIVES......................................................................................................................17
The objectives of this drug intensive monitoring study are to monitor and assess the safety profile 
of Compound Sodium Picosulfate Granules in the real world clinical practice in Chinese 
population, including：...........................................................................................................17
3
METHODS .........................................................................................................................................18
3.1
Study Design ...........................................................................................................................18
3.2
Medicinal Product ...................................................................................................................18
3.3
Bias and Limitations................................................................................................................18
3.3.1
Method to Minimize Bias............................................................................................18
3.3.2
Study Limitations........................................................................................................18
4
SELECTION OF STUDY POPULATION......................................................................................20
4.1
Study Population .....................................................................................................................20
4.1.1
Inclusion Criteria .......................................................................................................20
4.1.2
Exclusion Criteria ......................................................................................................20
4.2
Withdrawal Criteria.................................................................................................................20
4.3
Site Selection...........................................................................................................................20
4.4
Duration of Study ....................................................................................................................20
5
STUDY PROCEDURES....................................................................................................................21
The study procedure includes following steps: ....................................................................................21
6
SAFETY REPORTING.....................................................................................................................22
6.1
Definition of Adverse Events ..................................................................................................22
6.2
Definition of Adverse Drug Reactions ....................................................................................22
6.3
Definition of Unexpected Adverse Drug Reactions................................................................22
6.4
Definition of Serious Adverse Events .....................................................................................23
6.5
Collection of Adverse Events..................................................................................................24
6.6
Follow-up of Adverse Events..................................................................................................24
6.7
Adverse Events Recording during Case Processing................................................................25
6.7.1
Verbatim/Description of AE .......................................................................................26
6.7.2
Time Recording of AE ................................................................................................26
6.7.3
Outcome of AE............................................................................................................26
6.7.4
Assessment of AE........................................................................................................26
6.7.5
Special Situations of AE Recoding .............................................................................27
6.7.6
Special Situations with No Need to Record as AEs....................................................28
6.8
Reporting of Adverse Drug Reactions to Regulatory Authorities...........................................28
6.9
Post-study Safety Collection ...................................................................................................29
6.10
Special Situations ....................................................................................................................29
7
STATISTICAL METHODS..............................................................................................................31
7.1
Sample Size .............................................................................................................................31

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7.2
Analysis Population Definitions..............................................................................................31
7.3
Statistical Analysis ..................................................................................................................31
7.3.1
Demographics and other Baseline Characteristics....................................................31
7.3.2
Subject Disposition.....................................................................................................31
7.3.3
Safety Evaluation........................................................................................................31
7.4
Interim Analyses......................................................................................................................32
8
DATA HANDLING............................................................................................................................33
9
QUALITY CONTROL......................................................................................................................34
9.1
Monitoring...............................................................................................................................34
9.2
Audit/Inspection ......................................................................................................................34
10
CHANGES IN CONDUCT OF THE STUDY.................................................................................35
10.1
Protocol Amendments .............................................................................................................35
10.2
Premature Termination of Study Sites.....................................................................................35
11
REPORTING AND PUBLICATION...............................................................................................36
11.1
Non-Interventional Study Report ............................................................................................36
11.2
Confidentiality and Ownership of Study Data.........................................................................36
11.3
Publication and Public Disclosure...........................................................................................36
11.3.1 Publication Policy ......................................................................................................36
11.3.2 Public Disclosure Policy............................................................................................36
12
ETHICAL AND REGULATORY ASPECTS .................................................................................37
12.1
Ethics Committee ....................................................................................................................37
12.2
Regulatory Authority(ies) Authorisation / Approval / Notification ........................................37
12.3
Subject Information and Consent ............................................................................................37
12.4
Confidentiality of Subject Data...............................................................................................37
13
ARCHIVING ......................................................................................................................................39
14
MILESTONES....................................................................................................................................40
15
REFERENCES...................................................................................................................................41
16
APPENDICES ....................................................................................................................................43

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LIST OF ABBREVIATIONS
ADR
Adverse drug reaction
AE
Adverse event
AESI
Adverse event of special interest
BHPM
Bis-(p-hydroxyphenyl)-pyridyl-2-methane
BMI
Body Mass Index
CRO
Contract research organization
EC
Ethics committee
ECG
Electrocardiogram
ePRO
Electronic patient reported outcomes
FDA
U.S. Food and drug administration
GPP
Good pharmacoepidemiology practice
ICF
Informed consent form
ICSR
Individual case safety report
INR
International standardized ratio
NMPA
National medical products administration
PEG
Polyethylene glycol
PSUR
Periodic safety update report
PT
Preferred terms
RA
Regulatory authority
RMP
Risk management plan
SAE
Serious adverse event
SADR
Serious adverse drug reaction
SMP
Safety management plan 
SOC
System organ classification
SOP
Standard operating procedure

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1
INTRODUCTION
1.1
Background
High-quality bowel preparation plays an important role in ensuring a safe and successful X-ray 
examination, endoscopy or some kinds of bowel surgeries. Inadequate bowel preparation may lead to 
incomplete examination of the colonic mucosa, may require increased operation time and difficulty, 
and incur the costs for rescheduling or performing other examinations. Early attention to the 
influencing factors of bowel cleansing effect and taking positive measures can effectively improve the 
success rate and diagnosis rate of endoscopic and radiological examinations, and reduce the possibility 
of postoperative complications and local infections1–4. In 2019, China released the latest "Guidelines 
for Bowel Preparation Related to Digestive Endoscopy", emphasizing the importance of dietary 
restrictions and patient notification and education. The “Guideline” also recommends that sodium 
picosulfate, magnesium oxide, and anhydrous citric acid can be used for bowel preparation before 
endoscopy and is well tolerated (recommended strength: weak; evidence quality: moderate) 5. The 
other used colonic cleansing agents also include polyethylene glycol (PEG) electrolyte powder, 
magnesium salt, sodium phosphate, mannitol and Chinese herbal medicine. Each carries its own 
properties, indications and safety profiles.
Compound Sodium Picosulfate Granules is a compounded preparation consisting of sodium 
picosulfate and magnesium citrate. Each sachet contains 10 mg of sodium picosulfate, 3.5 g of 
magnesium oxide and 12.0 g of citric acid. It is white to slightly yellow crystalline powder, with a 
slight orange flavour. Sodium picosulfate is transformed by colonic bacteria to form an active 
metabolite: bis-(p-hydroxyphenyl)-pyridyl-2-methane, BHPM, which acts directly on the colonic 
mucosa to stimulate colonic peristalsis. Magnesium oxide and citric acid react to create magnesium 
citrate (when dispersed in a solution), which is an osmotic agent that causes water to be retained within 
the gastrointestinal tract. The stimulant laxative activity of sodium picosulfate together with the 
osmotic laxative activity of magnesium citrate produces a purgative effect, which can be used to clean 
the bowel prior to X-ray examination, endoscopy or bowel surgery.
Since its first marketing in the UK in December 1980, Compound Sodium Picosulfate Granules
has been approved in more than 80 countries and regions, including Germany (2010), France (2010), 
Spain (2011), Italy (2011) and the United States (2012), Japan (2016), under the tradename PICOLAX, 
PICOPREP or PREPOPIK. In 2018, Compound Sodium Picosulfate Granules was officially approved 
in China with the indication: for preparation of bowel cleansing prior to X-ray examination, endoscopy 
or surgery when judged clinically necessary.

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1.2
Preliminary Safety Evaluation
1.2.1
Preclinical Safety Data
The preclinical safety data related to Compound Sodium Picosulfate Granules are summarized as 
follows:
General Safety Pharmacology
Anesthetized rats were injected with sodium picosulfate intravenously and tested their cardiac 
function parameters. Under the maximum dose of 160 mg/kg, no abnormal changes in blood pressure 
and electrocardiogram were observed 6.
Irwin screen test was used to evaluate the effect of one-time oral gavage of sodium picosulfate on
the central nervous system of mice. Single oral administration of sodium picosulfate 40mg/kg and 
80mg/kg in mice has no effect on the central nervous system 6.
In a 4-week repeated oral dose toxicity study of Compound Sodium Picosulfate Granules in dogs 
(n = 6), no abnormal ECG changes were observed under the maximum dose of 1000 mg/kg (twice a 
day, every 8 hours apart).
Repeat-Dose Toxicity
Repeated dose toxicity studies with sodium picosulfate (2 weeks) and Compound Sodium 
Picosulfate Granules (4 weeks) in both the rat and the dog showed expected treatment and dose related 
pharmacology with soft stools and diarrhoea and with no observed adverse effects.
Carcinogenicity
No published studies of carcinogenic potential of sodium picosulfate have been identified.
Genotoxicity
Sodium picosulfate was not mutagenic in the Ames test, the mouse lymphoma assay and the 
mouse bone marrow micronucleus test.
Reproductive toxicity
Male and female rat fertility was not affected by oral doses of sodium picosulfate up to 100 mg/kg.
Prenatal developmental studies in rats and rabbits did not reveal any teratogenic potential after 
oral dosing of sodium picosulfate, but embryotoxicity has been observed in rats at 1000 and 10000 
mg/kg/day and in rabbits at 1000 mg/kg/day. The corresponding safety margins were 3000 to 30000 
times the anticipated human dose. In rats, daily doses of 10 mg/kg during late gestation (fetal 
development) and lactation reduced body weights and survival of the offspring. 

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In an oral fertility study in rats, Compound Sodium Picosulfate Granules did not cause any 
significant adverse effect on male or female fertility parameters up to a maximum dose of 2000 mg/kg 
twice daily (about 1.2 times the recommended human dose based on the body surface area). During 
the perinatal period, rats were given Compound Sodium Picosulfate Granules 2000 mg/kg twice daily, 
and no significant effect on pup growth and development was observed.
Drug interactions
Sodium picosulfate and its active metabolite are not absorbed to any significant degree and there 
is no evidence of direct, time dependent or metabolism dependent inhibition on the major drug 
metabolizing cytochrome P450 enzymes in human liver microsomes and hepatocytes. 
Some medicines (e.g. tetracycline and fluoroquinolone antibiotics, iron, digoxin, chlorpromazine 
and penicillamine) have the potential to chelate with magnesium.
1.2.2
Clinical Safety Data
Up to May 2019, the cumulative number of subjects from completed clinical trials, for Compound 
Sodium Picosulfate Granules, is estimated to 1,974 subjects.
The key efficacy, safety results and exposures to investigational drug from the completed Ferring 
sponsored Phase 3-4 clinical trials are presented in the table below. 
Trial 
Code/Phase
Trial Design
Country
Compound 
Sodium 
Picosulfate 
Granules
Dose/Schedule
No. of Subjects
Results
2009-01
(Phase 3)
Multicentre, 
randomized, 
assessor-
blinded, 
active 
control, 
parallel-
group
US
Split-daya
Compound 
Sodium 
Picosulfate 
Granules: 305;
HalfLytely: 298;
Total: 603
Compound 
Sodium 
Picosulfate 
Granules superior to HalfLytely in 
overall colon cleansing (Aronchick 
Scale). 
No 
drug-related 
safety 
concerns or novel adverse events 
were 
observed. 
No 
clinically 
meaningful changes in laboratory 
tests, 
ECGs, 
or 
physical 
examinations, including multiple 
orthostatic pulse and blood pressure 
measurements were observed. The 
safety profile supported a positive 
benefit/risk ratio.
2009-02
(Phase 3)
Multicentre, 
randomized, 
assessor-
blinded, 
active 
US
Day-beforeb
Compound 
Sodium 
Picosulfate 
Granules: 296;
Compound 
Sodium 
Picosulfate 
Granules non-inferior to HalfLytely 
in 
overall 
colon 
cleansing 
(Aronchick Scale). No drug-related 
safety concerns or novel adverse 

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Trial 
Code/Phase
Trial Design
Country
Compound 
Sodium 
Picosulfate 
Granules
Dose/Schedule
No. of Subjects
Results
control, 
parallel-
group
HalfLytely: 302;
Total: 598
events were observed. No clinically 
meaningful changes in laboratory 
tests, 
ECGs, 
or 
physical 
examinations, including multiple 
orthostatic pulse and blood pressure 
measurements were observed. The 
safety profile supported a positive 
benefit/risk ratio.
999169 CS2
(Phase 3)
Multicentre, 
randomized, 
assessor-
blinded, 
active 
control, 
parallel-
group
China
Split-dayc
Compound 
Sodium 
Picosulfate 
Granules:150;
PEG-ELS:150;
Total: 300
Compound 
Sodium 
Picosulfate 
Granules non-inferior to PEG-ELS 
(polyethylene 
glycol 
4000-
electrolyte powder for oral solution) 
in overall bowel cleansing (Ottawa 
Scale), cleansing of each colon 
section, and overall fluid retention. 
There were no clinically significant 
differences in changes from baseline 
to post-treatment in clinical safety 
laboratory values, vital signs, ECG 
parameters, or physical examination 
findings. 
Compound 
Sodium 
Picosulfate Granules was superior to 
PEG-ELS in subject-rated outcomes.
000121
(Phase 3)
Multicentre, 
randomized, 
assessor-
blinded, 
parallel-
group
EU
Split-dosed
vs.
Day-
beforee
Split-dose: 73;
Day-before: 131;
Total:204
Subjects 
receiving 
the 
tailored 
schedule had 7-9 times greater odds 
of being a responder (Ottawa Scale) 
with regard to colon cleansing status 
when compared with day-before 
schedule. Subject convenience and 
satisfaction (ease of consuming, 
overall experience, taste, willingness 
and acceptance to use for future 
colonoscopy) were high for each 
schedule. No new safety signals were 
seen with either schedule.
000176
(Phase 3)
Multicentre, 
randomized, 
assessor-
blinded, 
active 
control, 
parallel-
group
Japan
Split-dayf vs.
Day-beforeb
Compound 
Sodium 
Picosulfate 
Granules Split-
day: 214; 
Compound 
Sodium 
Picosulfate 
Granules Day-
before: 212;
Results showed that both Compound 
Sodium Picosulfate Granules dosing 
schedules 
were 
non-inferior 
to 
Niflec, as judged by an Independent 
Central 
Judging 
Committee 
(Japanese Colon Cleansing Scale). 
Subjects 
considered 
Compound 
Sodium Picosulfate Granules more 
acceptable than Niflec, according to 
a questionnaire administered on the 
day of colonoscopy. No new safety 

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Trial 
Code/Phase
Trial Design
Country
Compound 
Sodium 
Picosulfate 
Granules
Dose/Schedule
No. of Subjects
Results
PEG-ELS: 211;
Total: 637
signals were seen with either 
schedule.
000253
(Phase 3)
Multicentre, 
randomized, 
assessor-
blinded, 
active 
control, 
parallel-
group
US
Split-daya
Compound 
Sodium 
Picosulfate 
Granules: 453;
Sodium 
picosulfate, 
magnesium 
oxide, and 
anhydrous 
citric acid pre-
mixed oral 
solution: 448;
Total: 901
The Sodium picosulfate, magnesium 
oxide, and anhydrous citric acid pre-
mixed 
oral 
solution 
treatment 
demonstrated statistically significant 
superiority over Compound Sodium 
Picosulfate Granules for the primary 
endpoint and the key secondary 
endpoint. Overall, the safety results 
did not indicate any safety concerns 
or 
signals 
for 
either 
bowel 
preparation.
000180
(Phase 4)
Multicentre, 
randomized, 
assessor-
blinded, 
active 
control, 
parallel-
group
Brazil
Split-daya
Compound 
Sodium 
Picosulfate 
Granules: 90;
Mannitol/
Bisacodyl: 89;
Total: 179
Results showed that Compound 
Sodium Picosulfate Granules is a 
tolerable and safe preparation for 
colon cleansing in preparation for a 
colonoscopy in adult subjects, but 
the 
objective 
of 
demonstrating 
superior efficacy over the active 
control was not achieved.
a：Split-day schedule: On the day before colonoscopy, first dose between 5:00 pm and 9:00 pm; on the day of 
colonoscopy, second dose approximately 5 hr before but no more than 9 hr prior to the procedure.
b：Day-before schedule: On the day before colonoscopy, one dose between 4:00 pm and 6:00 pm and another dose 
6 to 8 hr later between 10:00 pm and 12:00 am.
c：Split-day schedule: On the day before colonoscopy, first dose between 8:00 pm and 9:00 pm; on the day of 
colonoscopy, second dose 4 to 6 hr before colonoscopy.
d：Split-dose schedule: First dose 10 to 18 hr before colonoscopy and second dose 4 to 6 hr before colonoscopy.
e：Day-before schedule: On the day before colonoscopy, one dose prior to 8:00 am and another dose 6 to 8 hr 
later.
f：Split-day schedule: On the day before colonoscopy, first dose between 5:00 pm and 9:00 pm; on the day of 
colonoscopy, second dose at least 4 and up to 9 hr prior to colonoscopy.
* HalfLytely: (Powder: PEG-El (polyethylene glycol electrolyte solution) 3350/Sodium Chloride/Sodium 
Bicarbonate/KCL) and Bisacodyl Tablets Bowel Prep Kit.
In randomized, multicentre, controlled clinical trials, nausea, headache, and vomiting were the 
most common adverse reactions (>1%) following Compound Sodium Picosulfate Granules
administration. Since abdominal bloating, distension, pain/cramping, and watery diarrhoea are known 

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to occur in response to bowel cleansing preparations, these effects were documented as adverse events 
in the clinical trials only if they required medical intervention (such as a change in study drug or led 
to study discontinuation, therapeutic or diagnostic procedures, met the criteria for a serious adverse 
event), or showed clinically significant worsening during the study that was not in the frame of the 
usual clinical course, as determined by the investigator.
Limitations in respect to populations typically under-represented in clinical trial development 
programmes are presented as follows:
Paediatric population
In completed Ferring sponsored clinical trial for the paediatric population (000103), 
a total of 78 paediatric subjects were included (48 paediatric subjects were 
randomised to Compound Sodium Picosulfate Granules and 30 to PEG). The subjects 
were randomised to one of the treatment arms by age groups from 9-12 years and 13-
16 years. The Compound Sodium Picosulfate Granules age group 9-12 years received 
either 1/2 sachet x 2 or 1 sachet x 2, whilst the Compound Sodium Picosulfate 
Granules age group 13-16 years received 1 sachet x 2. The results of the trial 
demonstrated that the ‘1 sachet x 2 dose’ of Compound Sodium Picosulfate Granules
is a safe and efficacious preparation for colonoscopy in children aged 9-16 years.
Elderly
In the completed Ferring sponsored clinical trials 20% of patients were of ≥ 65 years 
of age. The overall incidence of treatment emergent adverse events was similar among 
patients of ≥ 65 and < 65 years of age, 73% and 71% respectively.
Pregnant/breastfeeding
women
Pregnancy
Compound Sodium Picosulfate Granules should not be used during pregnancy unless 
the clinical condition of the woman requires treatment. There are no adequate and 
well-controlled studies with Compound Sodium Picosulfate Granules in pregnant 
women. 
Breastfeeding women
Several drugs are excreted in human milk and caution should be exercised when 
Compound Sodium Picosulfate Granules is administered to a lactating woman. No 
formal studies have evaluated the transfer of Compound Sodium Picosulfate Granules
products into human milk, or its effect on lactation or on breastfed infants.
The active metabolite of sodium picosulfate, BHPM is absorbed from the 
gastrointestinal tract. BHPM, however, remained below the limit of detection (1 
ng/mL) in breast milk after both single and multiple doses of 10 mg/day 7. Although 
it is known that magnesium contained in Compound Sodium Picosulfate Granules is 
systemically absorbed in healthy volunteers, no information is available on the 
clinical use of magnesium citrate during lactation.
Patients with hepatic 
impairment
Not included in the clinical development program.
A dosage adjustment in patients with hepatic impairment is not considered needed as 
sodium picosulfate is converted to its active metabolite BHPM by colonic bacteria. 
Sodium picosulfate and its metabolite BHPM are mainly excreted in urine.
Patients 
with
renal 
impairment
Severely reduced renal function (creatinine clearance less than 30 mL/minute) is a 
contraindication. In patients with severely reduced renal function accumulation of 
magnesium in plasma may occur. Another preparation should be used in such cases.

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An analysis was performed as a post-approval commitment to the FDA. The objective 
was to retrospectively identify risk factors associated with the development of 
persistent or potential late decrease in renal function in subjects who had undergone 
colon cleansing with Compound Sodium Picosulfate Granules or HalfLytely in 
preparation for colonoscopy in Ferring Trials FE2009-01 and FE2009-028,9. This 
retrospective analysis of renal function in subjects supports the current labelling when 
the product is used per label instructions as well as confirming the validity of the 
current renal prescribing information to physicians and subjects.
Population 
with
relevant 
different
ethnic origin
Phase 3 trials have been conducted in different regions involving patients of different 
racial and ethnic origin. Although no formal analysis has been carried out, the safety 
and efficacy profile of Compound Sodium Picosulfate Granules is well established in 
these various populations.
Patients with low body
weight (BMI)
Limited data is available for treatment of patients with low body weight (BMI less 
than 18). 
1.2.3
Post-authorisation Experience
The cumulative exposure to Compound Sodium Picosulfate Granules from marketing experience 
calculated from 01 January 1999 up to and including 31 May 2019 is estimated to 53,654,394 patients. 
The calculation of exposure is based upon an assumption that the number of treatments is equivalent 
with number of patients exposed to Compound Sodium Picosulfate Granules. One treatment consists 
of 2 sachets, which corresponds to an adult dose.
The frequencies of the side effects are based on post-marketing experience and as outlined in the 
Compound Sodium Picosulfate Granules label.
System Organ Class
Common 
(≥1/100, ＜1/10)
Uncommon (≥1/1000,＜
1/100)
Not known (cannot be 
estimated from the 
available data)
Immune system disorder
Anaphylactic reaction,
hypersensitivity
Metabolism and nutrition 
disorders
Hyponatraemia
hypokalaemia
Nervous system
disorders
Headache
Epilepsy, grand mal 
convulsion, convulsions, 
confusional state
Gastrointestinal disorders
Nausea and proctalgia
Vomiting, abdominal 
pain, aphthoid ileal ulcers
Diarrhoea, faecal 
incontinence
Skin and subcutaneous 
tissue disorders
Rash (including
erythematous and
maculopapular rash,
urticaria, purpura)
1.3 Study Rationale 
Based on nearly 40 years’ clinical experience, Compound Sodium Picosulfate Granules has a well-

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established safety profile and treatment regimen that support a positive benefit/risk ratio.
According to the review of non-clinical, clinical and post-marketing data, the known adverse
effects of Compound Sodium Picosulfate Granules include anaphylactic reaction, hypersensitivity, 
hyponatraemia, hypokalaemia, confusional state including disorientation, headache, epilepsy, 
generalised tonic-clonic seizure, seizure, loss of consciousness or depressed level of consciousness, 
syncope, presyncope, dizziness, vomiting, nausea, abdominal pain, diarrhoea, ileal ulcers, anal 
incontinence, proctalgia, rash (including erythematous rash, maculo-papular rash, urticaria, purpura). 
According to the latest Compound Sodium Picosulfate Granules Risk Management Plan (RMP) 
(Ver. 2.0, 11 OCT 2019), Compound Sodium Picosulfate Granules has no important identified risks, 
no important potential risks, and no important missing information. Compound Sodium Picosulfate 
Granules's label and its package leaflet give essential information to healthcare professionals and 
patients on how the Compound Sodium Picosulfate Granules product should be used. Measures to 
minimise the risks identified for medicinal products include:
Specific information, such as warnings, precautions, and advice on correct use, in the package
leaflet and label addressed to patients and healthcare professionals;
Important advice on the medicine’s packaging;
The authorised pack size — the amount of medicine in a pack is chosen so to ensure that the 
medicine is used correctly;
The medicine’s legal status — the way a medicine is supplied to the patient (e.g. with 
prescription) can help to minimise its risks.
Together, these measures constitute routine risk minimisation measures. In addition, information 
about adverse reactions is collected continuously and regularly analysed, including individual case 
assessment and Periodic safety update report (PSUR) assessment so that immediate action can be taken 
as necessary. These measures constitute routine pharmacovigilance activities. According to NMPA 
Regulation Order No. 81 of Ministry of Health, the safety profile of a newly approved medicine needs 
to be intensively monitored in a real-world setting. This study will further assess Compound Sodium 
Picosulfate Granules utilisation and safety profile in bowel preparation prior to X-ray examination, 
endoscopy or surgery when judged clinically necessary in real-world clinical practice in Chinese 
population.

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2
STUDY OBJECTIVES 
The objectives of this drug intensive monitoring study are to monitor and assess the safety profile of 
Compound Sodium Picosulfate Granules in the real world clinical practice in Chinese population,
including：

Incidence of known ADRs

Observe occurrence of unexpected AEs/ADRs

Incidence and risk factors of SAEs/SADRs

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3
METHODS
3.1
Study Design
This is a multi-site, prospective, non-interventional study. The subject’s recruitment should not be 
influenced by the study protocol and should fall within the current practice.
Subjects who meet the requirements will be followed from signing the informed consent form
(ICF) to about 37(+2) hours after first medication to collect AEs, medications and other relevant 
information with remotely contacted by pharmacist and/or hospital staff. No additional assessments or 
tests considered as interventional will be required. Any adverse events collected during the subject's 
interview will be sent to the sponsor for case processing.
3.2
Medicinal Product 
This study does not provide treatment, the subjects must already have been prescribed Ferring 
Compound Sodium Picosulfate Granules. All directions for drug usage are solely at the discretion of 
the subject’s primary physician in accordance with his/her usual practice and should be consistent with 
the local prescribing information.
3.3
Bias and Limitations
3.3.1
Method to Minimize Bias
In order to limit this potential selection bias in the recruitment of subjects, the recruiter will be 
required to include all subjects who have been prescribed Ferring Compound Sodium Picosulfate 
Granules in a naturalistic fashion.
Since the AE information is collected through the report of subjects, while the missing 
information of AEs due to subjects failing to declare may be immeasurable. 
3.3.2
Study Limitations
This is a single arm observational study provides no comparative data. Therefore, whether the 
incidence of AEs in the Compound Sodium Picosulfate Granules group is higher or lower than the 
incidence in a non-exposed group can’t be determined.
In addition, observational data may miss some relevant information or loss follow-up, the quality
of data is not compatible to interventional study. The participants are voluntarily enrolled which may 

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have certain bias would not truly represent real world population or data.

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4
SELECTION OF STUDY POPULATION 
4.1
Study Population
4.1.1
Inclusion Criteria
1)
Agree to participate in this study and sign the ICF by subject or the legal representative.
2)
Subjects taking the compound sodium picosulfate granules drug in real clinical practice. 
4.1.2
Exclusion Criteria
1)
Subjects who are enrolled in other on-going studies, which prohibit any participation in this non-
interventional study.
4.2
Withdrawal Criteria
As this is a non-interventional study, no specific withdrawal criteria are specified. Subjects are 
free to withdraw consent at any time. Data will be collected up to the time of withdrawal of consent, 
and no additional information will be collected after this time.
4.3
Site Selection
This study is planned to be conducted in 20 pharmacies and hospitals in China mainland.
4.4
Duration of Study
The overall duration of the study for each subject will be from signing the ICF to about 37 (+2)
hours after the first medication. The sponsor will decide on the requirement for any follow-up of AEs 
persisting (see section 6.6).
The study will be considered as started when the first subject signs the ICF and will be considered 
as finished when the last subject’s data are fully collected. The overall study duration will be 
approximately 2 years.
The sponsor has the right to terminate this study/close the study sites in advance after consulting 
the relevant regulatory agency.

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5
STUDY PROCEDURES
The study procedure includes following steps:
1. Provide signed and dated written informed consent form prior to any procedure related to 
the study.
2. Evaluate subjects agreed to participate in study to make sure they meet inclusion and 
exclusion criteria.
3. Register eligible subjects and collect subject demographics and characteristics (gender, 
age, nation, height and body weight).
4. Follow up the eligible subjects 37 (+2) hours after the first medication.
For the subject who experienced AE, the following information will be collected to evaluate 
the safety profile of Compound Sodium Picosulfate Granules in real-world clinical practice. 
Medicinal information (administration time and dosage) and indication
Concomitant medications
Medical history
Relevant lab test and its result: for the subject who experienced AE, collect relevant lab tests 
and its results subjects may receive as much as possible
Safety evaluation
All stipulated events reported from signing the ICF to about 37(+2) hours after the first medication.
AE information include the nature, the start date and end date, the relationship to the medicinal product,
the seriousness, the outcome, and the use of corrective treatment, etc.

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6
SAFETY REPORTING
6.1
Definition of Adverse Events
Adverse event (AE) is any untoward medical condition or the deterioration of a pre-existing 
medical condition in a patient or clinical investigation subject administered a pharmaceutical product 
and which does not necessarily have a causal relationship with the treatment. An AE can therefore be 
any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or 
disease temporally associated with the use of a medicinal product, whether or not related to the 
medicinal product. An AE may be caused by the use of any medication (e.g. non-indications, combined 
use), any route of administration, prescription, dose (including overdose) and accidental injuries.
6.2
Definition of Adverse Drug Reactions 
An adverse drug reaction (ADR), contrary to an AE, is characterized by the suspicion of a causal 
relationship between the medicine and the occurrence, i.e. judged as being at least possibly related to 
treatment by the reporter or a reviewing health professional.
An ADR is a response to a medicinal product which is noxious and unintended. This includes 
adverse reactions which arise from:

The use of a medical product within the terms of the marketing authorization;

The use outside the terms of the marketing authorization, including overdose, off-label use, 
misuse, abuse and medication errors;

Occupational exposure.
6.3
Definition of Unexpected Adverse Drug Reactions
Unexpected adverse reaction refers to a drug reaction whose nature, severity, specificity, or 
outcome is not consistent with the term or description listed in the current local/regional label. This 
includes events that may be symptomatically and pathophysiological related to an event listed in the 
labelling but differ from the event because of greater severity or specificity. For example, under this 
definition, hepatic necrosis would be unexpected (by virtue of greater severity) if the labelling only 
referred to elevated hepatic enzymes or hepatitis. Similarly, cerebral thromboembolism and cerebral 
vasculitis would be unexpected (by virtue of greater specificity) if the labelling only listed cerebral 
vascular accidents. 

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"Unexpected," as used in this definition, refers to an adverse drug experience that has not been 
previously observed (i.e. not included in the label) rather than from the perspective of such experience 
not being anticipated from the pharmacological properties of the pharmaceutical product.
6.4
Definition of Serious Adverse Events
A serious adverse event (SAE) is defined as any untoward medical occurrence that at any dose 
that:
Results in death a
Is life-threatening b
Is a congenital anomaly/birth defect c
Results in persistent or significant disability/incapacity d
Results in unplanned inpatient hospitalisation or prolongation of existing hospitalisation e
Is an important medical event that may jeopardise the subject or may require intervention to 
prevent one of the outcomes listed above f
Further explanations for SAEs are as follows:
a.
Any deaths caused by AEs during the study period, including those that are completely 
unrelated to the medicinal product. Note: AE terms should be described as the lead cause of 
death (e.g. multiple organ dysfunction syndrome, pneumonia, myocardial infarction, etc. and 
with a fatal outcome but not death as an event), with the only exception being unknown causes 
of death (i.e. sudden or unexplained death), in which case the event term may be "death" or 
"sudden death".
b.
Life-threatening is an event that places the patient at immediate risk of death from the reaction 
as it occurred. It does not include a reaction that, had it occurred in a more severe form, might 
have caused death, e.g. drug-induced liver injury without hepatic failure.
c.
The term refers to any congenital anomaly/birth defect in the offspring of either patient who 
exposed to the medicinal product.
d.
The term refers to any condition that impairs physical/psychological well-being to the extent 
that the subject is unable to function normally. Physical disability may include, but is not 
limited to, permanent disability of locomotion or motility, but also systemic permanent 
dysfunction as development of heart failure, liver insufficiency or pulmonary fibrosis.

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e.
Hospitalisation is defined as at least one overnight formal admission into hospital, usually to 
perform additional tests, provide treatment that it is not possible to provide at home and/or to 
allow specific monitoring of the subject due to their unstable medical condition. 
Hospitalisation for a pre-planned or elective treatment/surgical procedure should not be 
reported as an SAE unless there are complications or sequelae which meet the criteria for 
seriousness described above. Hospitalization or prolongation of existing hospitalisation due 
to non-medical reasons / convenience or purely for the purpose of study does not meet the 
criteria for medical events and cannot be considered an SAE.
f.
Important medical events that may not result in death, be life-threatening, or require 
hospitalisation may be considered a significant adverse drug experience when, based upon 
appropriate medical judgment, they may jeopardize the patient and may require medical or 
surgical intervention to prevent one of the outcomes listed in this definition. Examples of such 
medical events include allergic bronchospasm requiring intensive treatment in an emergency 
room or at home, blood dyscrasias or convulsions that do not result in inpatient hospitalisation, 
or the development of drug dependency or drug abuse.
6.5
Collection of Adverse Events
The study will collect all stipulated events reported from signing the ICF to about 37(+2) hours
after the first medication. Sponsor will capture any adverse events collected during the subject's 
remotely contact by pharmacist or hospital staff. 
Pharmacist or hospital staff will report any adverse events collected during the subject's remotely 
contact to Ferring (E-mail: 
) within the following timelines: 
1)
Fatal events, whether they are related/unrelated, must inform the sponsor immediately (within 
24 hours of the knowledge of the event).
2)
All other AE reports must be sent to the sponsor within 3 calendar days of knowledge of the 
event or receipt of significant follow-up information.
6.6
Follow-up of Adverse Events
The sponsor will decide on the requirement for any follow-up of AEs persisting after 37(+2) hours
after the first medication. Generally, for all ADRs, pharmacist or hospital staff needs to follow up until: 
PPD

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1) Sufficient information has been obtained from the reporter; 
2) The reporter clearly stated that there was no further information or refused to follow up; 
3) There is no new information after two follow-ups, and further follow-up cannot obtain more 
information; 
4) The reporter cannot be contacted more than 3 times on different days. Follow-up records should 
be kept properly;
5）Mails and letters are returned and there are no other contact methods available.
For Fatal SADR, the following information should be collected promptly, includes: verifying, 
supplementing and improving information on death cases, drug use, occurrence, diagnosis and 
treatment of adverse reactions; information about drug storage, use, and occurrence of similar adverse 
reactions from medical institutions; if the subject is transferred for treatment, investigation should be 
carried out on the transfer treatment. In addition, the subject’s medical records, autopsy reports and 
other information should be collected according to the actual situation. During the investigation 
process, the quality of the product should also be reviewed, and quality inspection should be carried 
out if necessary.
6.7
Adverse Events Recording during Case Processing
The sponsor is responsible for case processing. During case processing, AE recording must be
based on subject’s reliable reporting. For each AE the following variables will be recorded:
Verbatim;
Date/time of AE start and stop;
Relationship to the medicinal product;
Action taken with regard to the medicinal product;
Outcome; 
Seriousness;
Criteria for seriousness (if applicable);
Date AE met criteria for seriousness (if applicable);
Date of hospitalisation and discharge (if applicable);
Date of death and reason (if applicable);
Autopsy report (if applicable).

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6.7.1
Verbatim/Description of AE
The recording of AEs should use diagnostic terms whenever possible. If the diagnosis cannot be 
confirmed, AE can be recorded for the symptoms, signs and abnormal examinations. The record should
be updated and reported as follow-up information if later diagnosis is confirmed. It should be ensured 
that each AE verbatim term consists of a single event, and one diagnosis, sign or symptom is an AE.
6.7.2
Time Recording of AE
The start date of the AE should be the date when the symptoms appear. If the AE is the 
deterioration of a pre-existing medical condition at the baseline, the start date is the date of the 
deterioration of the condition in the study. If the AE is new event in the study and upgraded to SAE, 
the SAE start date is still the original AE start date.
6.7.3
Outcome of AE
The outcome of the event will be described in terms of:
Recovered: Subject returned to the baseline state.
Recovering: Event has not been fully resolved, but the subject is already in the recovery phase.
Not recovered: Event is ongoing. e.g. irreversible congenital malformation.
Recovered with sequelae: Used only with persistent incapacity/life-long sequelae, e.g. 
blindness after diabetes mellitus, hemiparesis after stroke. 
Fatal: (S)AE stop date is the date of death. 
Unknown: Unknown to investigational personnel, e.g. patient lost to follow-up.
If the outcome is “recovered” or “recovered with sequelae” or “fatal” the AE stop date must be 
entered.
6.7.4
Assessment of AE
Causality Classification
Subject will assess causal relationship between the medicinal product and each AE, and answer 
“yes” or “no” to the question “Do you consider that there is a reasonable possibility that the event may 
have been caused by Compound Sodium Picosulfate Granules?”
During case processing, the sponsor will also assess the causality. The relationship of an AE with 
the medicinal product will be classified according to the following:

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Related: The AE follows a reasonable temporal sequence from the medicinal administration 
and cannot be reasonably explained by the subject’s clinical state or other factors (e.g. disease under 
study, concurrent diseases, and concomitant medications). It may be a known reaction to the drug under 
study or its chemical group or is predicted by known pharmacology and could not be ruled out with 
certainty.
Not related: The AE does not follow a reasonable sequence from the medicinal product 
administration or can be reasonably explained by the subject’s clinical state or other factors (e.g.
disease under study, concurrent diseases, and concomitant medications).
Assessment of Expectedness
The sponsor is responsible for assessment of expectedness.
6.7.5
Special Situations of AE Recoding
Persistent or Recurrent AEs
Persistent AEs are events that persist between assessment time points and no remission. During 
case processing, such events should be recorded only once. The initial date of the event should be 
recorded. If the event progresses into an SAE, a corresponding update should be made to reflect the 
situation.
Recurrent AEs are events that have been resolved between assessment time points but then 
recurred. Each recurrence of an AE should be recorded separately.
AEs Secondary to other Events
During case processing, in general, AEs secondary to other events (e.g. cascade events or clinical 
sequelae) should be recorded based on their main etiology, except for severe or serious secondary AEs. 
For a medically significant AE secondary to an initial event with a time interval, the AE should be 
recorded as an independent event.
Abnormal Medical Exam
Clinically significant medical exam abnormalities (such as vital signs, physical examination, 
blood routine, urine routine, blood biochemistry, ECG, etc.) found before the first medication can be 
recorded as a medical history/concomitant disease. The results of various medical exam after 
medication will be compared with the data from baseline and judged whether they are of clinical 
significance.
During case processing, medical exam abnormalities should be recorded as an AE if any one of 

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the following criteria is met:
The abnormality is associated with symptoms/signs. 
The abnormality requires required medical intervention (such as a change in medicinal product 
or led to study discontinuation, therapeutic or diagnostic procedures).
If the abnormality is a manifestation of a disease (e.g. increased alkaline phosphatase and total 
bilirubin levels accompanied by cholecystitis), only the diagnosis (i.e. cholecystitis) should be 
recorded as an AE. If the abnormality does not belong to any disease, the abnormality itself should be 
recorded as an AE, using relevant descriptors to indicate that the test result is higher or lower than the 
normal range (e.g. “blood sodium decreased” instead of “blood sodium abnormal”). If the diagnostic 
criteria are met, the clinical diagnosis should be used to record the AE. For example, a serum sodium 
level < 135 mmol/L can be recorded as “hyponatremia”.
6.7.6
Special Situations with No Need to Record as AEs
During case processing, the following situations collected will not be recorded as AEs:
The clinical adverse events that occurred before the medication will be recorded as pre-
treatment events rather than AEs.
Since abdominal bloating, distension and watery diarrhoea are known to occur in response to 
bowel preparations, these effects should be documented as AEs only if they require medical 
intervention (such as a change in study drug or led to study discontinuation, therapeutic or diagnostic 
procedures), or show clinically significant worsening during the study that is not in the frame of the 
usual clinical course.
X-ray examination, endoscopy or bowel surgery findings such as polyps and/or colorectal 
cancer do not need to be recorded as an AE as their diagnosis is the goal of the endoscopic examination. 
However, injuries / damages caused by inspections or surgical operations must be recorded as AEs.
6.8
Reporting of Adverse Drug Reactions to Regulatory Authorities
The sponsor will submit the ADR to the Regulatory Authorities according to current legislation,
and all have to comply with local legislation for safety reporting.

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6.9
Post-study Safety Collection
If pharmacist or hospital staff becomes aware of an ADR reported by subjects spontaneously after 
the end of the study, the case will have to be sent to the sponsor, regardless how long after the end of 
the study.
6.10
Special Situations
The following information must be collected and recorded during case processing regardless of 
the occurrence of AE.
·Medication error (including potential medication error and intercepted medication error)
·Off-label use
·Lack of efficacy 
₋
The drug was ineffective, did not work, or similar wording, or that the expected effect 
was not obtained (e.g. subject did not reach the clear yellow liquid poop stage) under the 
usage and dosage according to the locally approved label.
·Accidental/Occupational exposure
·Misuse/Abuse
·Overdose/Underdose
·Counterfeit/falsified products
·Suspected transmission of an infectious agent via a medicinal product
·Drug exposure to foetus via mother or father
₋
The pregnancy must be reported immediately and within 24 hours from the date of the 
awareness to the sponsor by completing and sending the “Pregnancy form”. Pregnancy 
itself is not regarded as an AE, however, any congenital anomaly/birth defect, 
spontaneous miscarriage, elective termination for medical reasons should be reported and 
handled as SAE. Pharmacist or hospital staff will continue to provide and record further 
information about the course and outcome of the pregnancy (spontaneous miscarriage, 
elective termination, ectopic pregnancy, normal birth, or congenital abnormality) by 
telephone follow-up. 
·AEs in infants following drug exposure from breastfeeding

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·Treatment non-compliance
₋
In this study, non-compliance of drug administration and liquid intake (see Section 7.3.4)
will be recorded as treatment non-compliance.
·Unexpected benefit
·Cases where the reported term does not reflect a specific reaction, for example “Adverse 
reaction or Adverse event”
·Product use issues
·Product quality issues (only when reported alongside other safety information e.g. an ICSR or 
other surveillance event (e.g. medication error)).
Details will be described in safety management plan (SMP).

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7
STATISTICAL METHODS
7.1
Sample Size 
Since the drug regulatory authority did not require specific population surveillance in this project, 
general population surveillance will be adopted. This study will not impose rigid rules on the sample 
size of specific populations. Sponsor will collect safety data as much as possible.
7.2
Analysis Population Definitions
Safety population: Subjects who has signed an ICF and has at least partially taken the drug. It 
is the primary population for safety evaluation in post-marketing intensive monitoring.
7.3
Statistical Analysis 
Analyses will be performed by sponsor or its representatives. Statistical methods will be primarily 
descriptive in nature. No formal statistical tests will be performed.
All statistical analyses will be presented overall. 
7.3.1
Demographics and other Baseline Characteristics
Demographic and baseline clinical characteristics analysis will be performed on the safety
population. Descriptive summary statistics (number of available data, number of missing data, mean, 
standard deviation, median, minimum and maximum for continuous data, and frequency count and 
percentage for categorical data) will be calculated for demographic and baseline clinical characteristics 
(e.g. gender, age, weight, etc.). 
Missing data will not be replaced but they will be displayed in all relevant tables.
7.3.2
Subject Disposition
The following will be summarized:
·Subject signed ICF;
·Subject has at least partially taken the drug;
·Subject allocation by site. 
7.3.3
Safety Evaluation
AEs will be coded using the latest version of MedDRA and presented as “Preferred Terms (PT) 

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and System Organ Classification (SOC)”.
Descriptive summary statistics of SAEs, AESIs and other nonserious AEs, related or unrelated to 
Compound Sodium Picosulfate Granules, will be presented. The main contents include the incidence, 
seriousness. of known ADRs/AEs and unexpected ADRs/AEs, as well as the occurrence of ADRs/AEs
in specific populations. The covariates like age, gender and relevant risk factors (e.g. decreased renal 
function, non-compliance of drug administration or liquid intake, etc.) for the AE will be examined.
Analyses and summary tables will be based upon the registry population.
Statistical analyses will present the overall results as well as separately for the specific
populations. 
7.4
Interim Analyses
No interim analyses are planned for this study.

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8
DATA HANDLING
This study collect AEs, medications and other relevant information with remotely contacted by 
pharmacist and hospital staff. The subjects’ data will be input into the database by the delegated staff. 
The subjects will be identified only by Study ID and subject number in the export database for analysis.
If the written informed consent of a subject is known not to be available in spite of it being
required, data for this subject is not entered into or is deleted from the export database.
The safety data (AEs report) filed in AE form will be input into Ferring global safety database. 
The sponsor is responsible for processing AE/ADR in the safety database.
The coding of AE, medical history, concomitant medication, concomitant non-drug therapies and 
concomitant surgery terms will be performed. Concomitant medications will be coded using the World 
Health Organisation Drug Dictionary (WHODRUG) and AEs/medical and surgical history and 
nondrug therapy terms will be coded using the latest version of MedDRA.
On request, Pharmacist or hospital staff will provide the sponsor with additional data relating to 
the study, duly anonymised and protected in accordance with applicable requirements.

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9
QUALITY CONTROL
9.1
Monitoring
Before the first subject is recruited into the study, sponsor will work with the investigational 
personnel to review and discuss the study protocol and related documents, as well as their 
responsibilities with regards to protocol compliance. Training will be conducted in accordance with 
the prescribed study procedures, and records of all participants will be kept.
Sponsor reserves the rights of monitoring the data to verify that they are accurate and complete and 
that the study is conducted in compliance with the protocol, GPP and regulatory requirements. Assigned 
monitors will conduct a combination of remote data reviews (with email and telephone contacts) and 
periodic local visits to address specific requirements and data quality. The monitor can access all 
original data, documents and records of the study and perform source data verification including 
verification of informed consent of participating subjects. 
All the monitoring activities will be performed in accordance with sponsor SOP.
9.2
Audit/Inspection
Similarly, audits/inspections may be conducted during the study and/or at the end of the study by
representatives of the sponsor or external competent authorities. In this later case, the sponsor will be 
informed immediately. The auditor can review all medical records, study-related documents, and the 
ICF. The purpose of an audit is to ensure that ethical, regulatory and quality requirements are fulfilled 
in all studies performed by the sponsor.

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CHANGES IN CONDUCT OF THE STUDY
10.1
Protocol Amendments
Any change to this protocol will be documented in a protocol amendment, issued by the sponsor.
Amendments will be submitted for consideration to the approving central ethics committee (EC) and/or 
RA, as applicable. Approval is required for amendments which could affect the safety of the subjects, 
or which entails a change to the scope/design of the study.
10.2
Premature Termination of Study Sites
The sponsor reserves the rights to terminate the participation of individual study sites. Conditions 
that may warrant termination include but are not limited to, insufficient adherence to protocol 
requirements and failure to enter subjects at an acceptable rate.

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11
REPORTING AND PUBLICATION
11.1
Non-Interventional Study Report
The data and information collected during this study will be reported in a drug intensive 
monitoring study report prepared by the sponsor or its designee.
11.2
Confidentiality and Ownership of Study Data
Any information relating to the medicinal product or the study, including any data and results from 
the study is confidential information and will be the property of the sponsor. The investigational
personnel will protect the confidentiality of this proprietary information belonging to the sponsor and 
not disclose such information unless in accordance with the drug intensive monitoring study agreement 
agreed between the sponsor and the implementing party.
11.3
Publication and Public Disclosure
11.3.1
Publication Policy
The procedures for scientific result publication and authors involved in these publications and
communications will be defined by the sponsor which reserves the worldwide copyright of all-
important publications, including translations into other languages.
The sponsor reserves the rights to:

Use the study results for any regulatory procedure, on its own behalf or that of subsidiaries.

Present the results in its medical information letter on drugs.

Distribute reprints of the publications.
No one may use these rights without the prior written authorization of the sponsor.
11.3.2
Public Disclosure Policy 
The sponsor
will register
non-interventional studies in an
appropriate registry, i.e. 
www.ClinicalTrials.gov, (a website maintained by the National Library of Medicine (NLM) at the U.S. 
National Institutes of Health (NIH)) and any local registries as required by local/national legislation.

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ETHICAL AND REGULATORY ASPECTS
12.1
Ethics Committee 
A central EC will review the protocol and amendments in accordance with applicable national 
requirements. The central EC will review the Subject Information and the ICF, their updates (if any), 
and any written materials given to the subjects.
12.2
Regulatory Authority(ies) Authorisation / Approval / Notification
The permission to perform the study will be obtained in accordance with applicable national 
regulatory requirements. All ethical and or regulatory approvals in accordance with national legislation 
must be available before the study is initiated.
12.3
Subject Information and Consent
Prior to any procedure related to the study, informed consent must be obtained from subjects. 
Informed consent can be expressed verbally or in writing, an official ICF must be dated and signed 
personally by the subject (or witness/legal representative, if applicable). 
The investigational personnel will explain the nature, purpose, possible risk and benefit of the 
study to each subject (or witness/legal representative, if applicable). The subject must be given ample 
time to consider participation in the study, before the consent is obtained. Each subject will be informed 
that he/she is completely free to refuse to enter the study or to withdraw from it at any time, without 
any consequences for his/her further care and without the need to justify their decision. In case the 
subject decides to withdraw from the study, the data collected up to this point will be used.
Concerning the study data, the subject will accept by signing the ICF that their medical records 
may be viewed by the sponsor, RA, a mandated auditor and/or the study monitor in compliance with 
the statement of confidentiality.
12.4
Confidentiality of Subject Data
The investigational personnel will ensure that the confidentiality of the subjects’ data will be 
preserved. In the database or any other documents submitted for AE reporting or publication, the 
subjects will not be identified by their names, but by an identification system, which consists of an 

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assigned number in the study. Subject number will consist of site code “CHN##” and subject code 
“####” (E.g. Subject number: CHN01-0001). Documents that contain the confidential subject
identification, e.g. the signed ICF, will be maintained in strict confidence.

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ARCHIVING 
All relevant materials related to this study must be properly preserved, including original 
medical records (raw data), statistical data and the resulting documents. No local study document may 
be destroyed without the sponsor’s prior written agreement. The sponsor must be notified if the study 
documents are transferred to another party or moved to another location.
The intensive monitoring data and study documents should be retained in Ferring in accordance 
with its procedures and applicable regulatory requirements for at least 10 years after the completion of 
the study report.

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14
MILESTONES
Milestone
Planned date
Registration of drug intensive monitoring
Dec 2020
Start of data collection
Apr 2021
End of data collection
Dec 2022
Final report of study results
Feb 2023

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15
REFERENCES
(1) Winawer, S. J.; Zauber, A. G.; Ho, M. N.; O’Brien, M. J.; Gottlieb, L. S.; Sternberg, S. S.; Waye, 
J. D.; Schapiro, M.; Bond, J. H.; Panish, J. F.; Ackroyd, F.; Shike, M.; Kurtz, R. C.; Hornsby-
Lewis, L.; Gerdes, H.; Stewart, E. T. Prevention of Colorectal Cancer by Colonoscopic 
Polypectomy. 
New 
England 
Journal 
of 
Medicine
1993, 
329
(27), 
1977–1981. 
https://doi.org/10.1056/NEJM199312303292701.
(2) Harewood, G. C.; Sharma, V. K.; de Garmo, P. Impact of Colonoscopy Preparation Quality on 
Detection of Suspected Colonic Neoplasia. Gastrointestinal Endoscopy 2003, 58 (1), 76–79. 
https://doi.org/10.1067/mge.2003.294.
(3) Froehlich, F.; Wietlisbach, V.; Gonvers, J.-J.; Burnand, B.; Vader, J.-P. Impact of Colonic 
Cleansing on Quality and Diagnostic Yield of Colonoscopy: The European Panel of 
Appropriateness of Gastrointestinal Endoscopy European Multicenter Study. Gastrointestinal 
Endoscopy 2005, 61 (3), 378–384. https://doi.org/10.1016/S0016-5107(04)02776-2.
(4) Rabeneck, L.; Paszat, L. F. Circumstances in Which Colonoscopy Misses Cancer. Frontline 
Gastroenterol 2010, 1 (1), 52–58. https://doi.org/10.1136/fg.2009.000257.
(5) 中国医师协会内镜医师分会消化内镜专业委员会; 中国抗癌协会肿瘤内镜学专业委员会. 
中国消化内镜诊疗相关肠道准备指南(2019,上海). 中华消化杂志2019, 39 (7), 438–443. 
https://doi.org/10.3760/cma.j.issn.0254-1432.2019.07.002.
(6) Pala, G.; Coppi, G.; Crenscenzi, E. On the Laxative Properties of Sulfuric Esters of Phenols, with 
Particular Reference to 4,4′-(2-Picolylidene)-Bis-Phenylsulfuric Acid Disodium Salt 
(Picosulfol). Arch Int Pharmacodyn Ther 1966, 164, 356–369.
(7) Friedrich, C.; Richter, E.; Trommeshauser, D.; de Kruif, S.; van Iersel, T.; Mandel, K.; Gessner, 
U. Absence of Excretion of the Active Moiety of Bisacodyl and Sodium Picosulfate into Human 
Breast Milk: An Open-Label, Parallel-Group, Multiple-Dose Study in Healthy Lactating Women. 
Drug Metab. Pharmacokinet. 2011, 26 (5), 458–464. https://doi.org/10.2133/dmpk.dmpk-11-rg-
007.
(8) Rex, D. K.; Katz, P. O.; Bertiger, G.; Vanner, S.; Hookey, L. C.; Alderfer, V.; Joseph, R. E. Split-
Dose Administration of a Dual-Action, Low-Volume Bowel Cleanser for Colonoscopy: The SEE 
CLEAR 
I 
Study. 
Gastrointest. 
Endosc.
2013, 
78
(1), 
132–141. 
https://doi.org/10.1016/j.gie.2013.02.024.

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(9) Katz, P. O.; Rex, D. K.; Epstein, M.; Grandhi, N. K.; Vanner, S.; Hookey, L. C.; Alderfer, V.; 
Joseph, R. E. A Dual-Action, Low-Volume Bowel Cleanser Administered the Day before 
Colonoscopy: Results from the SEE CLEAR II Study. Am. J. Gastroenterol. 2013, 108 (3), 401–
409. https://doi.org/10.1038/ajg.2012.441.

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16
APPENDICES
Drug intensive monitoring synopsis (for RA China)
Generic Name: Compound Sodium Picosulfate 
Granules
Trade Name:
Formulation and Specification:
Packaged in two sachets, each sachet contains 
16.1 g of white or faintly yellow crystalline 
granules or powder. 
Ingredient/Component:
Each sachet contains: 10 mg sodium picosulfate, 
3.5 g magnesium oxide, 12.0 g citric acid.
Domestic first approval date:
23 Oct 2018
New drug monitoring period starting and end 
date:
23 Oct 2018 to 22 Oct 2021
Domestic marketing date:18 Mar 2019
International birth date: 22 Dec 1980
Intensive monitoring reasons:
New drug monitoring period first import within 
5 years, regulatory authority’s requirement
Implementation provinces:
Intensive monitoring (proposed) start date:
Apr 2021
Intensive monitoring end date:
Dec 2022
Funding support：
Total expenditure：
Relevant information of responsible party:
Ferring Pharmaceuticals (China) Co., Ltd.
Address: No.6, Hui Ling Lu (Ferring Road), National Health Technology Park 528437 Zhongshan 
City, Guangdong Province, People's Republic of China
Leader Name: 
E-Mail:
Materials submission (List in chronological order) ：
PPD
PPD

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Intensive monitoring objectives：
To monitor and assess the safety profile of Compound Sodium Picosulfate Granules in the real-
world clinical practice in Chinese population.
Summary of monitoring methods：
This is a post-marketing multi-centre, prospective, non-interventional study. Subjects who have 
been prescribed Ferring Compound Sodium Picosulfate Granules at the participating sites will be 
enrolled. The study will collect all stipulated events reported from signing the ICF to about 37(+2)
hours after first medication. Pharmacist or hospital staff will contact subjects remotely to collect 
adverse events/reactions and other relevant information. No additional tests or examinations will be 
performed on subjects.

The investigational personnel (e.g. pharmacy pharmacist or hospital staff) will register the 
eligible subjects. The subjects will sign the informed consent, record contact information.

After the procedure (about 37 (+2) hours after first drug administration) will report any adverse 
events and relevant information.

Follow up, if necessary, pharmacist or hospital staff will collect AEs and other relevant 
information.
Summary of monitoring results：
Notes：