Pill Swallow Study
Phase: NA
Conditions: Not Determined
Sponsor: RANI Therapeutics

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CP-0003

In Production
Pill Swallow Study Protocol
Revision  »C - ECO-002760
Effective as of 2021/05/24 01:52:07 PM, Unshared
Category
 Rani Therapeutics
Item
Number
CP-0003
Revision
C
Item Name
Pill Swallow Study Protocol
Lifecycle
Phase
In Production
Assembly
Type
Not an assembly
Primary
File
CP-0003 Rev C Pill Swallow Study Protocol
20210506
Associated
Files
13 (plus 0 Supplier Item files)
Description
Owner
Joshua Myers
Prototype
Cost
Production
Cost
Procureme
nt Type
Off-the-Shelf (OTS)
Unit Of
Measure
each
Item
Creator
Joshua Myers
Item
Created On
2021/02/02 01:50:18 PM

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All information contained in this document is proprietary and confidential.
ECO-002742

Pill Swallow Study Document Updates
Completed
Basic Information
Category
Engineering Change Order
Change Number
ECO-002742
Title
Pill Swallow Study Document Updates
Description
- CP-0003: Protocol updated to version B to change the pill contents from 
microcrystalline cellulose to potato starch and include a new exclusion criteria for 
allergies to mock-RaniPill components.
- Summary of changes for the protocol added
- Updated all CRFs to replace "subject" with "participant" and add a version date.
Additional CRF Edits:
- Screening CRF: Added new exclusion criteria for allergies to mock-RaniPill components. 
Moved Pill Swallow Assessment up the form.
- Post-Swallow Questionnaire: changed VAS score from 0-10 to 0-4.
- SAE Form: added "Final Outcome" field.
Associated Files
10 Reference File(s) + 0 Implementation File(s)
Routings
None specified
Approval Deadline
None specified
Effectivity
2021/04/28
Expiration Date
N/A (This is a permanent Change.)
Lifecycle Status...
Completed
...As Of
2021/04/28 03:38:17 PM
Creator
Joshua Myers
Created On
2021/04/23 06:53:40 AM
Submitter
Joshua Myers
Submitted On
2021/04/23 11:30:50 AM

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Reason and Justification
Impact Assessment
Company/Project
Rani
Reason and
Justification for
Change
Protocol updated to version B to change the pill contents from microcrystalline cellulose to
potato starch and add a new exclusion criteria. CRFs updated while creating the database
and accommodating protocol changes.
Are other documents
affected by this
change?
No
Other affected
documents
N/A
Design V&V Testing
required?
No - Provide justification below.
Design V&V Testing
additional
info/justification
N/A
Process Validation
required?
No - Provide justification below.
Process Validation
additional
info/justification
N/A
Risk Analysis update
required?
No - Provide justification below.
Risk Analysis
additional
info/justification
N/A
Regulatory Action
required?
No - Provide justification below.
Regulatory Action
additional
info/justification
N/A
Supplier/Partner
notification required?
No
Supplier/Partner
notification
additional info
N/A
Training or re-
training required?
No

PILL SWALLOW STUDY PROTOCOL 
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Pill Swallow Study 
 
Clinical Study Protocol 
 
 
 
 
Sponsor: 
Rani Therapeutics 
2051 Ringwood Ave 
San Jose, CA 95131 
 
 
 
 
This study will be conducted in compliance with the Clinical Study Protocol, Good Clinical 
Practices and applicable local and national regulatory requirements. 
 
Confidential Information 
No use or disclosure of this document outside Rani Therapeutics is permitted without prior 
written authorization from Rani Therapeutics. 
 

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ABBREVIATIONS 
Abbreviation Definition 
AE 
Adverse Event 
CFR 
Code of Federal Regulations 
CIP 
Clinical Investigation Plan 
CRF 
Case Report Form 
CTA 
Clinical Trial Agreement 
CTM 
Clinical Trial Material 
CV 
Curriculum Vitae 
eCRFs 
Electronic Case Report Forms 
EDC 
Electronic Data Capture 
EMA 
European Medicines Agency 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice 
GET 
Gastric Emptying Time 
GI 
Gastrointestinal Tract 
IB 
Investigator’s Brochure 
ICF 
Informed Consent Form 
ICH 
International Conference of Harmonization 
ICMJE 
International Committee of Medical Journal Editors 
IDT 
Intestinal Deployment Time 
IRB 
Institutional Review Board 
NSR 
Non-Significant Risk 
PI 
Principal Investigator 
SAE 
Serious Adverse Event 
US 
United States 
 
 

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PROTOCOL SYNOPSIS 
Title 
Pill Swallow Study 
Purpose 
A Prospective Study Assessing Participant Experience with Swallowing a Mock Version 
of the RaniPill™ Capsule (“Mock-RP”) 
Phase of Clinical 
Trial 
Non-significant risk 
Test Device 
Mock-RP: Standard 000 capsule shell filled with potato starch weighing similar as the 
RaniPill™ Capsule, enteric-coated with colorant and lubricous coating 
Indication for Use 
N/A 
Study Objective 
Assess a participant’s ability to swallow a Mock-RP. 
Sample Size 
Up to 200 participants will be enrolled with up to 150 participants attempting to 
swallow the Mock-RP: 30 to 50 participants in each age group.  Participation inclusion in 
an age group stops at 50 participants. 
Follow-up 
Assessment of the Mock-RP will occur the same day as swallowing the pill.  No 
additional follow-up is anticipated. 
General Study 
Design 
A prospective, single-center, open-label, single-arm, observational study enrolling up to 
200 men and women volunteers age ≥21 currently using injection therapy to treat 
chronic disorders (e.g., diabetes (I or II), rheumatoid arthritis, ulcerative colitis, Crohn's 
disease, ankylosing spondylolisthesis, psoriasis, growth hormone deficiency, hemophilia 
A) recruited from the general population with up to 150 participants attempting to 
swallow the Mock-RP after passing protocol required screening. A total of 30 to 50 
participants will be included in each of the following age ranges: 21-50, 51-65, 66-75. 
Participants must meet all inclusion and none of the exclusion criteria prior to 
attempting to swallow the Mock-RP. Participants will complete a questionnaire on their 
thoughts on an alternative therapy in pill form. Upon completion of the questionnaire, 
participants will be requested to swallow a Mock-RP.  The Mock-RP will be a standard 
000 capsule filled with potato starch weighing similar to the RaniPill™ Capsule.  The 
capsule is protected by an enteric coating with colorant and lubricious coating allowing 
intact passage through the stomach into the jejunum, where the pH starts dissolving 
the coating; completely dissolving in the small intestine. After swallowing the Mock-RP, 
the participant will complete the questionnaire assessing swallowability of the Mock-
RP. If the participant was unable to swallow the Mock-RP, they will be asked to attempt 
to swallow a Calcium dietary supplement (Rapid Release Calcium in Liquid Softgel). 
Anticipated participant duration is approximately 1 hour. 
Inclusion Criteria 
Individuals eligible to participate in this study must meet all the following criteria: 
1. 
Participant age is 21 – 75 years 
2. 
Participant understands the nature of the study, is willing to comply with protocol 
defined evaluations, and provide written informed consent  
3. 
Participant currently taking injections to treat a chronic disorder 
4. 
Non-pregnant, non-lactating female 
NOTE: Females who are of childbearing potential must have had a negative 
pregnancy test on day of screening 

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Exclusion Criteria 
Individuals eligible to participate in this study must not meet any of the following 
criteria: 
1. 
Active case of COVID-19. 
2. 
History of Dysphagia. 
3. 
History of dementia (e.g., Alzheimer’s, vascular dementia, dementia with Lewy 
bodies, etc.). 
4. 
Participant self-reports issues with swallowing pills. 
5. 
History of drug or alcohol abuse or any other factor that, in the Investigator’s 
opinion, may interfere with the participant’s ability to cooperate and comply with 
the study procedures. 
6. 
History of allergic reaction to a component of the Mock-RP 
7. 
History which, in the investigator’s judgement, makes the participant ineligible or 
exposes the participant to unacceptable risks 
Study Endpoints 
- 
Percent of participants successfully swallowing the Mock-RP as reported on the 
questionnaire. 
- 
Assess if participant would choose a pill instead of their current injection therapy if 
a pill becomes available. 
- 
Participant experience with swallowing Mock-RP stratified by number of years 
using injections. 
- 
Participant experience with swallowing Mock-RP stratified by age (21-50, 51-65, 
66-75 years). 
- 
Participant experience with swallowing Mock-RP stratified by frequency of 
injection treatment. 
- 
All adverse events categorized by type and frequency. 
Clinical Trial 
Material (CTM) 
Mock-RP 
Sponsor: 
Rani Therapeutics 
2051 Ringwood Ave 
San Jose, CA 95131 
 
 

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TABLE OF CONTENTS 
1 
INTRODUCTION................................................................................................................... 8 
1.1 
Study Purpose ..................................................................................................................... 8 
1.2 
Study Scope ........................................................................................................................ 8 
1.3 
Governing Regulations ....................................................................................................... 8 
2 
BACKGROUND AND JUSTIFICATION ........................................................................... 8 
2.1 
Mechanism of Action ......................................................................................................... 8 
2.2 
Summary of Prior Clinical Use/History ............................................................................. 9 
2.2.1 
Non-Significant Risk Study ........................................................................................ 9 
2.2.2 
First-In-Human Study ................................................................................................. 9 
2.3 
Justification ........................................................................................................................ 9 
3 
INTENDED USE, INDICATIONS FOR USE AND PRODUCT DESCRIPTION .......... 9 
3.1 
Intended Use ....................................................................................................................... 9 
3.2 
Proposed Indication for Use ............................................................................................. 10 
3.3 
Investigational Clinical Trial Material (CTM) Description ............................................. 10 
4 
METHODOLOGY AND ENDPOINTS ............................................................................. 10 
4.1 
Study Endpoints ............................................................................................................... 10 
4.2 
Minimization of Bias ........................................................................................................ 11 
5 
STUDY SAMPLE SIZE ....................................................................................................... 11 
6 
STUDY SITE INFORMATION .......................................................................................... 11 
6.1 
Agreements....................................................................................................................... 11 
6.2 
Institutional Review Board (IRB) .................................................................................... 11 
6.3 
Investigator Responsibilities ............................................................................................ 11 
6.4 
Sponsor Responsibilities .................................................................................................. 12 
6.5 
Study Training .................................................................................................................. 13 
6.6 
Site Selection .................................................................................................................... 13 
6.7 
Site Activation .................................................................................................................. 14 
7 
STUDY DESIGN ................................................................................................................... 14 
7.1 
Participant Selection ......................................................................................................... 14 
7.2 
Study Inclusion and Exclusion Criteria ............................................................................ 15 
7.2.1 
Inclusion Criteria ...................................................................................................... 15 
7.2.2 
Exclusion Criteria ..................................................................................................... 15 

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7.3 
Enrollment ........................................................................................................................ 15 
7.4 
Informed Consent Process ................................................................................................ 15 
7.4.1 
Protection of Participant Data ................................................................................... 17 
7.5 
Participant Accountability ................................................................................................ 17 
7.6 
Screening Procedures ....................................................................................................... 19 
7.6.1 
Pill Swallowing Issues .............................................................................................. 19 
7.6.2 
Clinical Examination ................................................................................................ 19 
7.6.3 
Concomitant Medications, Treatments, and Procedures........................................... 19 
7.6.4 
Urine Collection for Pregnancy ................................................................................ 20 
7.7 
Visit Procedures ............................................................................................................... 20 
7.7.1 
Pre-Swallow Questionnaire ...................................................................................... 20 
7.7.2 
Mock-RP Swallowing ............................................................................................... 20 
7.7.3 
Post-Swallow Questionnaire ..................................................................................... 20 
7.7.4 
Calcium Pill Swallowing, if necessary ..................................................................... 20 
7.7.5 
Unscheduled Visits ................................................................................................... 20 
7.7.6 
Participant Withdrawal Criteria ................................................................................ 20 
8 
INVESTIGATIONAL CTM HANDLING AND TRACEABILITY ............................... 20 
9 
STUDY DEVIATIONS ......................................................................................................... 21 
10 ADVERSE EVENTS DEFINITIONS AND REPORTING .............................................. 22 
10.1 
Adverse Event............................................................................................................... 22 
10.2 
Serious Adverse Events (SAE) ..................................................................................... 22 
10.3 
Unanticipated Problems ................................................................................................ 22 
10.4 
Adverse Event Relatedness .......................................................................................... 22 
10.5 
Adverse Event Severity ................................................................................................ 23 
10.6 
Deaths ........................................................................................................................... 23 
10.7 
Anticipated Adverse Events ......................................................................................... 23 
10.8 
Adverse Event Reporting .............................................................................................. 24 
11 BENEFIT-RISK ANALYSIS ............................................................................................... 24 
11.1 
Potential Risks .............................................................................................................. 24 
11.2 
Potential Benefits .......................................................................................................... 24 
12 EARLY TERMINATION .................................................................................................... 25 
13 STATISTICAL METHODS ................................................................................................ 25 

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13.1 
Analysis Cohorts........................................................................................................... 26 
13.2 
Sample Size Justification .............................................................................................. 26 
14 DATA AND QUALITY MANAGEMENT ......................................................................... 26 
14.1 
Electronic Case Report Forms ...................................................................................... 26 
15 AMENDMENTS TO THE PROTOCOL ........................................................................... 27 
16 MONITORING, AUDITING AND INSPECTING ........................................................... 27 
16.1 
Monitoring Plan ............................................................................................................ 27 
16.2 
Access to Study Records .............................................................................................. 27 
17 REQUIRED RECORDS AND REPORTS ......................................................................... 27 
17.1 
Investigator Records ..................................................................................................... 27 
17.2 
Investigator Reports ...................................................................................................... 28 
17.3 
Sponsor Records ........................................................................................................... 29 
17.4 
Sponsor Reports ............................................................................................................ 29 
18 PUBLICATIONS .................................................................................................................. 30 
19 REFERENCES ...................................................................................................................... 30 
 
TABLE OF FIGURES 
Figure 1: Enteric-coated Capsule .................................................................................................... 10 
Figure 2: Participant Accountability Overview .............................................................................. 18 
 
TABLE OF TABLES 
Table 1: Screening and Visit Requirements.................................................................................... 19 
Table 2: Investigator Reporting Requirements ............................................................................... 28 
Table 3: Sponsor Reporting Requirements ..................................................................................... 29 
 
 
 

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1 INTRODUCTION 
1.1 
Study Purpose 
Rani Therapeutics is sponsoring the Pill Swallow Study, a prospective, single-center, open-label, 
single-arm, observational study assessing participant experience with swallowing the Mock-RP. 
1.2 
Study Scope 
This study will be conducted at one site in the U.S. Up to 200 participants will be enrolled 
(consented) and up to 150 will attempt to swallow the Mock-RP after passing protocol required 
screening. Study duration is expected to be approximately three months.  
1.3 
Governing Regulations 
The Mock-RP is investigational and classified as a non-significant risk device in the U.S. This Clinical 
Investigation Plan (CIP) will not be submitted to the FDA for approval. The study will be conducted 
per 21 CFR Parts 11 (Electronic Records; Electronic Signatures), 50 (Protection of Human Subjects), 
and 56 (Institutional Review Boards) and conducted in accordance with the relevant parts of the 
ICH Guidelines for Good Clinical Practice, ethical principles that have their origins in the 
Declaration of Helsinki and the individual country laws and regulations, whichever afford greater 
protection to participants. Participating sites will obtain IRB approval prior to beginning study. 
2 BACKGROUND AND JUSTIFICATION 
The RaniPill™ Capsule is an ingestible robotic pill, based on 000 (31 mm by 11 mm) size capsule 
designed to deliver biopharmaceuticals into the small intestinal wall. The goal of the RaniPill™ 
Capsule is orally deliver biologics which are currently given via subcutaneous, intramuscular or 
intravenous injections. The current study will evaluate the ease of swallowing of a pill similar in 
size to RaniPill™ Capsule.  
2.1 
Mechanism of Action 
The RaniPill™ Capsule needs to be swallowed whole to keep its internal delivery mechanism intact. 
The RaniPill™ Capsule remains intact in the stomach, protected by the enteric coating. As it leaves 
the stomach and advances along the small intestine by peristalsis, the enteric coating starts to 
dissolve with the rise in pH. Dissolution of the enteric coating and capsule shell exposes the 
reaction valve to the intestinal fluid, causing its dissolution and enabling the mixing of citric acid 
and potassium bicarbonate. The production of carbon dioxide inflates and stabilizes the balloon 
and aligns the micro syringe perpendicularly to the intestinal wall and, as the piston is released, 
drives the dissolvable needle into the wall. The microneedle dissolves within minutes and delivers 
its payload, while the balloon deflates, releases the carbon dioxide, and is excreted through the 
gastrointestinal tract (GI). 

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2.2 
Summary of Prior Clinical Use/History 
2.2.1 Non-Significant Risk Study 
In a non-significant risk (NSR) study, a modified, needleless, medication-free version of the 
RaniPill™ Capsule was tested in 10 fasting and 10 postprandial healthy volunteers to examine the 
tolerability of the RaniPill™ Capsule ingestion, gastrointestinal progression, deployment and 
ultimate excretion of the device remnants, monitored with serial abdominal fluoroscopies. A 
single RaniPill™ Capsule was orally administered to each subject and radiographically tracked 
during its transit from the stomach to the small intestine. No adverse events were reported by the 
subjects in the study. 
2.2.2 First-In-Human Study 
This study was the first demonstration in humans (N=62) of the oral delivery of an injectable 
biotherapeutic via the orally ingestible RaniPill™ Capsule. This study suggested RaniPill™ Capsule 
may safely and effectively deliver a wide variety of biotherapeutics currently administered only 
via parenteral routes. Biotherapeutic was successfully delivered with a bioavailability of 65%.  All 
devices were confirmed to have successfully been excreted by all subjects without sequelae. No 
serious or unexpected adverse events were observed during the transit of the RaniPill™ Capsule 
through the gastrointestinal tract. 
2.3 
Justification 
In the previous studies, none of the participants reported any issues with swallowing the RaniPill™ 
Capsule. These studies were conducted in young healthy volunteers.  The goal of the present study 
is to enroll patients of different age groups who are taking injections and will be potential 
candidates for the RaniPill™ Capsule when it becomes available. Understanding patient treatment 
preference is important in early drug development. Collecting data on patient preference of new 
and current therapies may help inform the benefit-risk assessment of the product (Bouvy 2020). 
The ease of swallowing oral drug therapy is a key determinant for patient acceptability. The 
European Medicines Agency (EMA) in 2017 released a reflection paper regarding pharmaceutical 
development of medicines for use in older populations and suggested swallowability and 
palatability are key characteristics for patient acceptability (EMA 2017). Ternik, et al., conducted 
a workshop dedicated to acceptability assessments for pediatric pharmaceutical products with 
similar conclusion of swallowability and palatability contributing to oral drug acceptability in 
pediatric patients (Ternik 2018). Swallowability and palatability ratings of new oral drug therapies 
may drive patient selection to new oral therapies vs their current injection options. 
The study will test the swallowability of a pill similar in shape and size to the RaniPill™ Capsule to 
be referred to as Mock-RP. 
3 INTENDED USE, INDICATIONS FOR USE AND PRODUCT DESCRIPTION 
3.1 
Intended Use 
The Mock-RP is not intended to deliver a treatment for a disease. 

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3.2 
Proposed Indication for Use 
The Mock-RP will not be used to treat disease in participants. 
3.3 
Investigational Clinical Trial Material (CTM) Description 
In this study, a Mock-RP capsule shell, similar to weight, shape and size of the RaniPill™ Capsule, 
will be filled with potato starch, enteric-coated with colorant and lubricous coating (Figure 1).  
 
Figure 1: Enteric-coated Capsule 
The potato starch is considered natural and produced directly from a peeled, ground, washed and 
dried potato. The Mock-RP is an investigational CTM and will be manufactured by Rani 
Therapeutics. The Mock-RP will not contain a needle or drug and will be packaged and labeled 
individually in a plastic vial with a snap on cap. The Mock-RP will be delivered directly to the 
investigator by the sponsor’s representative and stored at room temperature under standard 
security protocols. 
4 METHODOLOGY AND ENDPOINTS 
The objective of this study is to assess a participant’s ability to swallow a Mock-RP. 
Eligible participants will complete a questionnaire to assess their experience on an alternative 
therapy in pill form. Upon completion of the questionnaire, participants will be requested to 
swallow a Mock-RP then complete a questionnaire assessing a participant’s ability to swallow the 
Mock-RP. Anticipated participant duration is approximately 1 hour. 
4.1 
Study Endpoints 
Several endpoints will be evaluated, including: 
• Percent of participants successfully swallowing the Mock-RP as reported on the 
questionnaire. 
• Assess if participant would choose a pill instead of their current injection therapy if a pill 
becomes available. 
• Participant experience with swallowing Mock-RP stratified by number of years using 
injections. 
• Participant experience with swallowing Mock-RP stratified by age (21-50, 51-65, 66-75 
years). 
• Participant experience with swallowing Mock-RP stratified by frequency of injection 
treatment. 
• All adverse events categorized by type and frequency. 

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4.2 
Minimization of Bias 
Potential sources of bias in this study may result from selection of participants, treatment of 
participants, and evaluation of study data. The following methods have been incorporated into 
the study protocol to minimize potential bias: 
• Participants will be screened to confirm eligibility for enrollment with defined 
inclusion/exclusion criteria prior to Mock-RP swallowing attempt. 
• All Site and Sponsor personnel will be trained on their respective aspects of the study using 
standardized training materials. 
• All study personnel will be trained on and required to follow the CIP. 
• All study investigators will be required to provide Financial Disclosure. 
• Rani Therapeutics will monitor the investigation for adherence to GCP the CIP and accurate 
data reporting. 
5 STUDY SAMPLE SIZE 
As a prospective, single-center, open-label, single-arm, observational study, no statistical criteria 
for sample size are required. A total of 30 to 50 participants in each age group (21-50, 51-65, 66-
75), for a total of up to 150 participants will provide sufficient data to characterize the endpoints, 
as well to evaluate swallowing trends between subgroups. 
6 STUDY SITE INFORMATION 
6.1 
Agreements 
Rani Therapeutics will sign a Clinical Trial Agreement (CTA) between Rani Therapeutics and the 
principal investigator (PI) and/or investigative site. This agreement will outline the financial and 
contractual arrangements between the parties. 
6.2 
Institutional Review Board (IRB) 
IRB approval of the current CIP, Informed Consent Form (ICF), and any other study materials 
provided to prospective participants is required prior to enrolling any participants. Recruitment 
materials must be approved by the IRB before their presentation to prospective participants. 
Continuing review is required throughout the duration of the study until the time of study closure. 
6.3 
Investigator Responsibilities 
Before participating in the study, all Investigators must agree to respect and fulfill the terms of 
this Investigational Plan.  
• The investigator is responsible for ensuring this study is conducted according to the signed 
agreements, this CIP, all applicable regulations, and any conditions imposed by the IRB. 

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• The investigator is responsible for obtaining the written and dated approval/favorable 
opinion of the IRB for the clinical investigation before obtaining informed consent or 
allowing any participant to participate. 
• The investigator is responsible for ensuring all IRB policies and procedures are followed. 
• The investigator is responsible for protecting the rights, safety, and welfare of participants 
under the investigator’s control. 
• The investigator is responsible for obtaining informed consent. 
• The investigator must document and explain any deviation from this CIP. 
• The investigator is responsible for control of study CTM in his or her facility and must 
ensure they are only used by authorized persons for participants in this study and must 
ensure they are returned to Rani Therapeutics when requested. 
• An investigator must disclose sufficient conflicts of interest, including financial 
information. The investigator must promptly update the information if any relevant 
changes occur throughout the study and for one year following study closure. 
• The investigator must maintain a list of appropriately qualified persons to whom the 
investigator has delegated study activities. This document is referred to as the Delegation 
of Authority Log for this study. Even though tasks may be delegated, the investigator is 
ultimately responsible for the conduct of the study at his or her institution. The 
investigator must not allow persons on the delegation log to perform study activities until 
they are trained by the Rani Therapeutics study team. 
• The investigator must have sufficient time and resources to properly conduct and 
complete the study. 
• The investigator must maintain accurate and complete records relating to the 
investigation. 
• The investigator must be responsible for all study related medical decisions and ensure 
that adequate medical care is provided to a participant for adverse events. 
The investigator should ensure the accuracy, completeness, and timeliness of all data and reports 
submitted to Rani Therapeutics and the IRB. 
6.4 
Sponsor Responsibilities 
The Sponsor responsibilities include, but are not limited to: 
• Selecting appropriately qualified principal investigators. 
• Providing investigators with the information they need to conduct the investigation 
properly. 
• Ensuring proper monitoring of the investigation. 

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• Securing compliance and maintain records to document the compliance of all parties 
involved in the clinical investigation. 
Rani Therapeutics and industry personnel can provide technical support to the Investigator and 
other health care personnel (collectively HCP) as needed during testing required by the protocol 
and follow-ups. Support may include HCP training, addressing HCP questions, or providing 
clarifications to HCPs concerning the procedures and forms related to the protocol. 
In addition, Rani Therapeutics may perform certain activities to ensure study quality. These 
activities may include: 
• Observing testing to provide information relevant to protocol compliance. 
• Reviewing collected data and study documentation for completeness and accuracy. 
Rani Therapeutics will not: 
• Practice medicine. 
• Provide medical diagnosis or treatment to participants. 
• Discuss a participant’s condition or treatment with a participant without the approval and 
presence of the HCP. 
• Independently collect critical study data. 
• Enter data in electronic data capture systems. 
6.5 
Study Training 
Persons who conduct study activities under this CIP must be trained prior to performing study 
activities.  The site PI must be trained before the site may be activated.  PIs will be trained on the 
following: 
• CIP, including but not limited to visit procedures, informed consent, investigator 
responsibilities, investigational CTM usage and handling, data collection, electronic data 
capture system, adverse events, reporting requirements, participant withdrawal, and 
study deviations. 
• ICH Guideline on Good Clinical Practices (GCP) E6, Section 4, Investigator 
• Investigator responsibilities described in 21 CRF 312 Subpart D 
All other site and sponsor personnel who perform study activities must be trained on study 
activities relevant to their roles and responsibilities. 
6.6 
Site Selection 
Sites will be selected based on research infrastructure, the availability of the potential participant 
pool that meets study inclusion criteria, and the site’s ability to perform the research in 
compliance with the CIP. 

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6.7 
Site Activation 
Site activation is defined as the point in time where the sponsor notifies the PI in writing that the 
study may begin, and participants may be consented (enrolled) at his or her site. All local 
regulatory requirements must be fulfilled before the site can be activated. Rani Therapeutics will 
provide each PI written notification upon site activation. The following must be complete and 
received by Rani Therapeutics prior to a site’s activation: 
• Financial Disclosure Form: The PI must disclose any financial arrangements he or she has 
with Rani Therapeutics that meet the following requirements per 21CFR54: 
o Payment to the PI that could be influenced by the outcome of the trial 
o Any other significant payments (≥ $25,000), such as research grants, consulting, 
etc. 
o Any proprietary interest in the investigational CTM 
o Any significant equity interest in Rani Therapeutics (≥ $25,000) 
• Confirmation that PI has completed study training 
• IRB approval of the CIP 
• IRB approved ICF 
• Current Curriculum Vitae (CV) of the PI 
• Fully executed CTA between Rani Therapeutics and the PI and/or Institution 
Other study site personnel, including sub-investigators, may not participate in study activities until 
compliance with all individual requirements are documented.   
The following must be completed before individual site personnel may perform study activities: 
• Site activation must be complete (the PI must have all aforementioned items completed) 
• Training pertinent to the individual’s role 
• Individuals must be named on the list of appropriately qualified persons to whom the 
investigator has delegated significant study-related duties 
• Current CV (for sub-investigators only) 
• Financial Disclosure Form (for sub-investigators only) 
7 STUDY DESIGN 
This is a prospective, single-center, open-label, single-arm, observational study assessing 
participant experience with swallowing the Mock-RP. 
7.1 
Participant Selection 
Participants ≥21 years old who are currently taking injections to treat chronic disorders (e.g., 
diabetes (I or II), rheumatoid arthritis, ulcerative colitis, Crohn's disease, ankylosing 
spondylolisthesis, psoriasis, growth hormone deficiency, hemophilia A) will be enrolled. 

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7.2 
Study Inclusion and Exclusion Criteria 
Upon confirmation that a consented participant meets all inclusion criteria and none of the 
exclusion criteria, the participant is considered eligible for randomization, and the study 
procedure can be scheduled. 
7.2.1 Inclusion Criteria 
Individuals eligible to participate in this study must meet all the following criteria: 
1. Participant age is 21 – 75 years 
2. Participant understands the nature of the study, is willing to comply with protocol defined 
evaluations, and provide written informed consent  
3. Participant currently taking injections to treat a chronic disorder 
4. Non-pregnant, non-lactating female 
NOTE: Females who are of childbearing potential must have had a negative pregnancy test 
on day of screening 
7.2.2 Exclusion Criteria 
Individuals eligible to participate in this study must not meet any of the following criteria: 
1. Active case of COVID-19 
2. History of Dysphagia 
3. History of dementia (e.g., Alzheimer’s, vascular dementia, dementia with Lewy bodies, 
etc.) 
4. Participant self-reports issues with swallowing pills. 
5. History of drug or alcohol abuse or any other factor that, in the Investigator’s opinion, may 
interfere with the participant’s ability to cooperate and comply with the study procedures 
6. History of allergic reaction to a component of the Mock-RP 
7. History which, in the investigator’s judgement, makes the participant ineligible or exposes 
the participant to unacceptable risks 
7.3 
Enrollment 
Up to 200 men and women volunteers age ≥21 currently using injection therapy will be recruited 
from the general population and enrolled (consented) and up to 150 participants will attempt to 
swallow the Mock-RP after passing protocol required screening. A total of 30 to 50 participants 
will be included in each of the following age (years) groups: 21-50, 51-65, 66-75. Participants must 
meet all inclusion and none of the exclusion criteria prior to swallowing the Mock-RP.  
7.4 
Informed Consent Process 
Informed Consent is a legally effective, documented confirmation of a participant’s voluntary 
agreement to participate in a clinical investigation after the information has been given to the 
participant on all aspects of the clinical investigation that are relevant to the participant’s decision 
to participate. The ICF will be approved by an IRB prior to the commencement of the clinical 
investigation at an investigative site.  Any changes to the ICF must be approved by the IRB 

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reviewing the application before being used to consent a prospective study participant. It is 
recommended, but not required, that changes made to the ICF be submitted to Rani Therapeutics 
for review prior to being used to consent a prospective study participant. The current IRB 
approved version of the ICF must be used. Participants must provide informed consent prior to 
any study-related procedures. 
The process of obtaining a participant’s informed consent will: 
• Ensure that the PI or his/her authorized designee conducts the informed consent process 
• Include all aspects of the clinical investigation that are relevant to the participant’s decision 
to participate throughout the clinical investigation 
• Provide opportunity for participant to ask questions  
• Avoid any coercion or undue improper influence on, or inducement of, the participant to 
participate 
• Not waive or appear to waive participant’s legal rights 
• Use native language that is non-technical and understandable to the participant 
• Provide ample time for the participant to read and understand the informed consent form 
and to consider participation in the clinical investigation 
• Ensure participant, or an authorized designee responsible for conducting the informed 
consent process, dates and signs the ICF. The investigator and research staff cannot sign 
or date the ICF for the participant. 
• The original signed and dated ICF and documentation of the consent process must be 
retained at the investigative site and available for monitoring and auditing.  
• Show how informed consent is obtained and recorded in special circumstances (e.g., 
participant needing legally designated representatives, participant unable to read or write) 
where the participant is unable to provide it 
• A copy of the signed and dated ICF (and data privacy language where required by law) must 
be provided to the participant (or person who signed the form in the case of a legally 
authorized representative).  
• Data protection authorization/or other privacy language needs to be collected where 
required by law or local regulation.  
• If using an electronic ICF, there needs to be a documented electronic signature process 
which is in compliance with applicable regulations (refer to 21 CRF part 11).  
• It is recommended that the informed consent process is documented in the participant’s 
medical records.  
Any new information should be provided to the participant if it could affect the participant’s 
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7.4.1 Protection of Participant Data 
The Sponsor and any designated CROs will make every reasonable effort to protect the 
confidentiality of the participants participating in the study. Except as required by law, participants 
will not be identified by name, social security number, address, telephone number, or any other 
direct personal identifier. A unique identification code will be assigned to each participant 
participating in this study. Information about the code will be kept in a secure location by the 
Investigator. All participant data will be stored in locked offices. All electronic data will be 
password-protected on computers stored in locked offices. Access to participant information will 
be limited to study personnel only. Any data, including photographs, that may be published in 
abstracts, scientific journals, or presented at medical meetings will reference a unique participant 
code and will not reveal the participant’s identity without the express approval of the participant. 
It is possible that participant personal health records may be disclosed to other agencies such as 
regulatory bodies as per country regulations. 
Data storage will reside at the clinical research sites and at Rani Therapeutics. Sites will retain data 
collected during the clinical trial for a minimum of 15 years. Sponsor will retain data per company 
Standard Operating Procedures. 
The HIPAA requirements affect clinical trials in three key areas as described below: 
• Accounting of Disclosures: Data collected during the conduction of prescreening activities 
for this clinical trial are participant to the HIPAA accounting of disclosures’ regulations. It 
is the responsibility of the investigative center to tell all participants whose records were 
screened for eligibility in the trial that their records were used in this manner if he or she 
requests an accounting of when his or her data were disclosed. 
• Consent: All participants in the clinical trial will be made aware that their participation in 
the clinical trial will involve disclosure of certain protected health information to Rani 
Therapeutics and for what purpose. The Informed Consent form will contain a listing of the 
type of information that will be disclosed during the clinical trial. 
• Withdrawal of Consent: HIPAA specifically allows companies such as Rani Therapeutics 
participant to jurisdiction of the FDA access to protected health information for activities 
related to the quality, safety or effectiveness of devices. This means that Rani Therapeutics 
can use data from this clinical trial even if the individual withdraws his or her authorization. 
7.5 
Participant Accountability 
Following completion of screening, participants will be assigned to their age group and have one 
study visit to swallow the Mock-RP and complete questionnaires (Figure 2). 

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Pre-screen
Consented 
(enrolled)
Protocol 
Required 
Screening
Age: 66-75
N=50
Age: 21-50
N=50
Age: 51-65
N=50
Complete Pre-Swallow Questionnaire
Complete Post-Swallow  Questionnaire
Study Exit
Up to 150
No
Successfully Swallow 
Mock-RaniPill
Yes
Attempt to Swallow 
Calcium Pill
Enrolled Screen 
Failure
Up to 200
Up to 50 Enrolled 
Screen Failures
 
Figure 2: Participant Accountability Overview 
 
 

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Screening and visit requirements are outlined in Table 1. 
Table 1: Screening and Visit Requirements 
  
Swallow Visit 
Inclusion/Exclusion criteria review 
√ 
Informed Consent 
√ 
Medical Hx/Demographics 
√ 
Weight/Height/Temperature 
√ 
Concomitant Medications 
√ 
Urine Pregnancy Test 
√^ 
Dispense Mock-RP 
√ 
Questionnaires 
√ 
Dispense Calcium Pill, if necessary 
√* 
Adverse Event(s) 
√ 
^ Pregnancy test completed on day of screening. 
* Dispense ONLY if participant is unable to swallow the Mock-RP 
7.6 
Screening Procedures 
All participants currently using injections at each participating investigational site should be 
evaluated for study eligibility. Participants may be recruited from clinical site databases, general 
population, using flyers, broadcast or web-based/social media. For participants who appear to 
meet study criteria, the Investigator (or designee) will discuss the study with the potential 
participant and ask him/her to consider study participation.  Along with other required elements, 
the background and purpose of the study, participation requirements, the potential benefits and 
risks of participation must be explained to the participant. If he/she agree, an Informed Consent 
Form (ICF) must be signed to document the consenting process. Prior to any non-standard-of-care 
procedures, the participant must sign the Informed Consent Form approved for use by the IRB. 
Participants must be provided a copy of the signed ICF for their reference.  
7.6.1 Pill Swallowing Issues 
Participants will report if they have issues swallowing pills. 
7.6.2 Clinical Examination 
A medical history focusing on, but not limited to, the 90 days before study day will be obtained.  
The history will review the use of medications, including prescription and non-prescription 
pharmaceuticals per Section 7.6.3 “Concomitant Medications, Treatments, and Procedures”. 
Height, weight, and temperature will be measured before administration of the Mock-RP capsule. 
7.6.3 Concomitant Medications, Treatments, and Procedures 
The concomitant prescription and non-prescription pharmaceuticals must be reported in the CRF 
at screening. For this protocol, a prescription medication is defined as one that can be prescribed 
only by a licensed physician. 

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7.6.4 Urine Collection for Pregnancy  
In women of childbearing potential, urine pregnancy tests will be performed the day of the study.  
Pregnancy tests are not required for surgically sterile or postmenopausal women. Tests will be 
performed on-site and results must be known before administration of the study CTM. 
7.7 
Visit Procedures 
7.7.1 Pre-Swallow Questionnaire 
Participant will complete the pre-swallow questionnaire to self-report any historical issues with 
swallowing pills, current medicines they take in pill form, and if they would take an alternative 
therapy in pill form. 
7.7.2 Mock-RP Swallowing 
The participant should rinse their mouth with water before swallowing the Mock-RP then swallow 
the pill the way they always swallow pills, without chewing. While swallowing, the participant 
should take into account how the pill feels on the surface of their tongue and palate. 
7.7.3 Post-Swallow Questionnaire 
Participant should complete the post-swallow questionnaire to report the palatability and 
swallowability of the Mock-RP. 
7.7.4 Calcium Pill Swallowing, if necessary 
Participants unable to swallow the Mock-RP on the post-swallow questionnaire (responded “No” 
to “Did you manage to swallow the pill?”) will be asked to attempt to swallow a Calcium dietary 
supplement (Rapid Release Calcium in Liquid Softgel – contains 600 mg calcium as calcium 
carbonate per softgel and 500IU Vitamin D as D3 Cholecalciferol per softgel). The participant 
should rinse their mouth with water before attempting to swallow the calcium pill then swallow 
the pill the way they always swallow pills, without chewing.  
7.7.5 Unscheduled Visits 
Participant study duration will be approximately 1-hour; thus, no unscheduled visits are 
anticipated in this study. 
7.7.6 Participant Withdrawal Criteria 
Participants can withdraw from the study at any time for any reason; the reason for withdrawal 
will be documented. All data available at the time of withdrawal (if any) will be used for analysis. 
There will be no further data collection per this study Investigation Plan on the participant who 
has withdrawn. 
8 INVESTIGATIONAL CTM HANDLING AND TRACEABILITY 
The Mock-RP is investigational and will be tracked from the time it is shipped and/or hand carried 
from Rani Therapeutics until it is either used in the study or returned to the sponsor. A CTM 

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Accountability Log will be maintained at each study site and will be provided by Rani Therapeutics 
in the Regulatory Binder. CTM allocated for site use will be recorded in the CTM Accountability 
Log upon delivery to the study site and will be stored in a secured area until use. The log should 
include: 
• name(s) of person(s) who received used, returned, or disposed of the CTM 
• The date of receipt, identification, and quantity of each CTM 
• The expiry date, if applicable 
• The date of use 
• Participant identification 
• The date of return of unused or expired CTM, if appliable 
• The date and documentation of disposal of the CTM as per instructions of the sponsor, if 
applicable. 
All unused study CTM must be returned to Rani Therapeutics.  
9 STUDY DEVIATIONS 
A study deviation is defined as an event within a study that did not occur according to the protocol 
or the CTA. Prior approval by Rani Therapeutics and IRB is expected in situations where the 
investigator anticipates, contemplates, or wishes to make a conscious decision to deviate if the 
deviation affects participant’s rights, safety, and well-being, or the scientific integrity of the clinical 
investigation. Prior approval is not required when a deviation is necessary to protect the life or 
physical well-being of a participant in an emergency or in unforeseen situations beyond the 
investigator’s control (e.g., participant failure to attend scheduled follow-up visits, inadvertent 
loss of data due to a computer malfunction, etc.). All study deviations must be reported regardless 
of whether medically justifiable, pre-approved by Rani Therapeutics, an inadvertent occurrence, 
or done to protect the participant in an emergency. The deviation must be recorded and 
documented in participant medical/research record with an explanation for the deviation. 
Reporting of deviations must comply with IRB policies, local laws, and/or regulatory agency 
requirements, if applicable.   
The PI shall notify Rani Therapeutics and the reviewing IRB of any deviation from this CIP affecting 
the participant’s rights, safety, and well-being of human participants under emergency 
circumstances. Notification must be given as soon as possible, but in no later than 5 working days 
after the emergency occurred. Rani Therapeutics is responsible for analyzing deviations, assessing 
their significance, and identifying any additional corrective and/or preventive actions (e.g., amend 
the CIP, conduct additional training, etc.).  Repetitive or serious investigator compliance issues 
may require initiation of a corrective action plan with the investigator, and in some cases, 
necessitate suspending site enrollment until the problem is resolved or ultimately terminating the 
investigator’s participation in the study.   

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10 ADVERSE EVENTS DEFINITIONS AND REPORTING 
10.1 Adverse Event  
Adverse Event (AE):  Any untoward medical occurrence, unintended disease or injury, or untoward 
clinical signs (including abnormal laboratory findings) in participants, users or other persons 
whether or not related to the investigational CTM. 
10.2 Serious Adverse Events (SAE) 
An adverse event is considered serious when it: 
• Led to death, 
• Led to serious deterioration in the health of the participant, that either resulted in 
o A life-threatening illness or injury, or 
o Permanent impairment of a body structure or a body function, or 
o In-patient or prolonged hospitalization, or  
o Medical or surgical intervention to prevent life-threatening illness or injury or 
permanent impairment to a body structure or a body function, 
• Led to fetal distress, fetal death or a congenital abnormality or birth defect 
All SAEs will be reported on the SAE report form. 
10.3 Unanticipated Problems  
Any unexpected, serious adverse effect on health or safety of participants having implications for 
the conduct of the study (e.g., requiring a significant and usually safety-related, change in the 
protocol such as revising inclusion/exclusion criteria or including a new monitoring requirement, 
informed consent, or investigator’s brochure) not previously identified in nature, severity, or 
degree of incidence in the study protocol, informed consent or investigator’s brochure. 
10.4 Adverse Event Relatedness 
The clinician’s assessment of an AE's relationship to the study CTM is part of the documentation 
process, though does not determine whether it is reported. Clinical observations suspected to be 
an AE must be reported. For all collected AEs, the clinician who examines and evaluates the 
participant will determine the AE’s causality based on temporal relationship and clinical judgment. 
The degree of certainty of causality will be graded as: 
• Definitely Related: There is unequivocal evidence of a causal relationship, and other 
possible contributing factors can be ruled out. The timing of a clinical event, including an 
abnormal laboratory test result, is related to the delivery of the study CTM and is not 
explained by a concurrent disease or other pharmaceuticals or chemicals. The response 
to withdrawal of the study CTM (de-challenge) should be clinically plausible. The event 
must be pharmacologically or phenomenologically definitive. The AE is expected to be 
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• Probably Related: There is evidence of a causal relationship, and the influence of other 
factors is unlikely. The clinical event, including an abnormal laboratory test result, occurs 
within a reasonable time after the administration of the study CTM, is unlikely to be due 
to a concurrent disease or other pharmaceuticals or chemicals, and responds as expected 
to a de-challenge. 
• Possibly Related: There is some evidence in favor of a causal relationship (e.g., the event 
occurred within a reasonable time after administration of the study CTM), though other 
factors may have contributed to the event (e.g., the participant’s clinical condition, other 
concomitant events). Although an AE may be listed as “possibly related” soon after its 
identification, it may be flagged as requiring more information and later upgraded to 
“probably” or “definitely” related, as appropriate. 
• Probably Not Related: A clinical event, including an abnormal laboratory test result, 
whose temporal relationship to the study CTM administration makes a causal relationship 
improbable (e.g., the event did not occur within a reasonable time after administration of 
the study CTM) and where other pharmaceuticals or chemicals, or an underlying disease 
provide a satisfactory explanation (e.g., the participant’s clinical status, a concomitant 
treatment). 
• Unrelated: The AE is completely independent of the administration of the study CTM, or 
the event is unequivocally due to another cause. There must be an alternate, definitive 
cause documented by the clinician. 
10.5 Adverse Event Severity  
Adverse event severity will be categorized using the following definitions: 
• Mild: Events require minimal or no treatment and do not interfere with the participant’s 
daily activities. 
• Moderate: Events result in minor inconvenience or concern with the therapy. Moderate 
events may interfere with some functions. 
• Severe: Events interrupt a participant’s usual daily activity and may require systemic drug 
therapy or other treatment. Severe events may be life-threatening or incapacitating. 
10.6 Deaths 
During the study, all deaths must be reported to Rani Therapeutics within 24 hours. A copy of the 
participant’s death records, medical records for the events that led to the participant’s death, and 
a death certificate (if available) should be provided. 
10.7 Anticipated Adverse Events 
Known potential risks of swallowing the Mock-RP include: 
• Oropharyngeal symptoms (coughing, gagging, etc.) 

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• Airway obstruction due to accidental aspiration 
• Dysphagia 
• Nausea/vomiting 
• Dyspepsia 
10.8 Adverse Event Reporting 
All adverse events occurring from the start of any study specific screening procedures must be 
recorded in the eCRF. Adverse events identified and reported in this study will be classified in 
accordance with the adverse event diagnosis and reported to the IRB per local requirements. 
AEs must be recorded on the eCRF and be described by (a) duration (start and resolution dates); 
(b) signs and symptoms; (c) final event diagnosis; (d) event severity; (e) Investigator’s clinical 
opinion on the relationship to the study CTM; (f) action taken to resolve the event; (g) outcome 
of the event; and (h) whether or not such event is considered to have been serious and/or 
unanticipated.  
Adverse events should be reported according to their underlying cause, if known. Multiple 
symptoms related to a single diagnosis should not be reported as separate AEs. Only concomitant 
AEs that are unrelated to each other (in the clinician’s judgment) should be reported as separate 
events. 
11 BENEFIT-RISK ANALYSIS 
The use of the Mock-RP may be associated with adverse effects; however, in this pill swallow 
study, the overall and serious adverse effect risks are anticipated to be low and very low, 
respectively. Most adverse effects, if any, are likely to occur during swallowing of the Mock-RP. 
11.1 Potential Risks 
There are risks to the participant associated with study participation. Risks are associated with 
administration of the Mock-RP (defined in section 10.7) and participation in a clinical study. The 
greatest risk of participating in this clinical study is loss of confidentiality. Every attempt will be 
made to ensure participant confidentiality. 
11.2 Potential Benefits 
There are no anticipated benefits from participation in this study other than free medical tests. 
Future clinical use of the RaniPill™ Capsule is likely to improve participants’ quality of life and 
increase their compliance with treatment by offering a needle-free alternative to repeated 
injections. 

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12 EARLY TERMINATION 
Rani Therapeutics may terminate Investigator and/or site participation in the study for issues 
including but not limited to the following: 
• Evidence of an Investigator’s failure to maintain adequate clinical standards  
• Evidence of an Investigator or staff’s failure to comply with the CIP 
• Inaccuracy or late submission of data forms  
• Conditions of approval imposed by the reviewing IRB 
• Evidence of safety concerns  
• Change of staff at site that adversely impacts study conduct 
Any evident pattern of non-compliance with respect to these standards will have corrective 
actions implemented. If corrective actions are not subsequently undertaken, the clinical site will 
be asked to withdraw from the study and their site may be replaced. 
If Rani Therapeutics terminates or prematurely suspends the study, the investigators will be 
promptly informed of the rationale. In the case of study termination or suspension for reasons 
other than a temporary IRB approval lapse, the investigator will promptly inform the IRB. In the 
case of study termination, the investigator must inform the participants.  
If the investigator terminates or suspends the study without the prior agreement of Rani 
Therapeutics, the investigator will promptly inform Rani Therapeutics and provide a detailed 
written explanation of the termination or suspension. The investigator will promptly inform the 
institution (where required per regulatory or local requirements), the IRB, and the participants. 
If the IRB terminates or suspends its approval of the study, the investigator will promptly inform 
Rani Therapeutics and provide a detailed written explanation of the termination or suspension. 
Participant enrollment must stop at the site until the IRB suspension is lifted. The investigator will 
inform his/her institution (where required per regulatory or local requirements). The investigator 
will promptly inform the participants of the rationale for the study termination or suspension. 
13 STATISTICAL METHODS 
Categorical data will be summarized using frequency tables, presenting the participant counts and 
relative percentages. Continuous variables will be summarized by the mean, standard deviation, 
median, minimum and maximum. The SAS system or equivalent statistical package will be used to 
perform all analyses. Exact confidence intervals will be generated for estimates of proportions.  
Asymptotic confidence intervals will be generated for estimates of means.  Except where 
otherwise noted, p-values of all tests will be reported without any correction for the multiplicity 
of tests performed.   

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13.1 Analysis Cohorts 
All participants who attempt to swallow the Mock-RP in the study are included in the Analysis 
Cohort used for evaluating swallowability of the Mock-RP.  
13.2 Sample Size Justification 
As an observational study, no hypothesis tests are planned.  All data will be summarized.  
Nevertheless, with the sample size proposed for the study, the following levels of precision of the 
estimates, expressed as the width of the confidence interval, can be achieved: 
1. The width of the exact 95% two-sided confidence interval for percentages will be no wider 
than +/- 14.5% with 50 participants contributing to the estimate of the proportion and will 
be no wider than +/- 8.3% with 150 participants. 
2. The width of the 95% two-sided confidence interval for the mean will be equal to +/- 27.7% 
of the standard deviation with 50 participants contributing to the estimate of the mean 
and will be equal to +/- 16.0% of the standard deviation with 200 participants. 
14 DATA AND QUALITY MANAGEMENT 
All information and data sent to Rani Therapeutics concerning participants or their participation 
in this study will be considered confidential. All data used in the analysis and reporting of this 
clinical study will be used in a manner without identifiable reference to the participant. The 
investigator consents to visits by Rani Therapeutics staff, contractors, and authorized 
governmental bodies to review the study participants’ medical records, including any test or 
laboratory data that might have been recorded on diagnostic test media. 
Data will be stored in a secure, password-protected database. Data will be reviewed using 
programmed and manual data checks. Data queries will be made available to sites for resolution. 
Study management reports may be generated to monitor data quality and study progress. At the 
end of the study, and any potential interim analysis, data will be frozen and retained by Rani 
Therapeutics. Procedures for data review, database cleaning, issuing and resolving data queries, 
verification, validation and securing of electronic clinical data systems, and data retention will be 
documented separately. 
14.1 Electronic Case Report Forms 
All required clinical data for this study will be collected in web-based standardized eCRFs. 
Participant IDs and initials (where allowed) will be used to track participant information 
throughout the study. The study database will be developed and maintained according to written 
procedures and will be compliant with signature requirements in 21 CFR 11.  
To facilitate transcription into the eCRFs, worksheets may be provided to the investigational sites. 

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15 AMENDMENTS TO THE PROTOCOL 
The study sponsor may request that the investigator submit an amendment to the protocol for 
IRB review if the sponsor proposes a change in the protocol that may affect its scientific soundness 
or the rights, safety, or welfare of participants. These amendments must be approved by the IRB 
before implementation. 
16 MONITORING, AUDITING AND INSPECTING 
16.1 Monitoring Plan 
During the course of the study, the sponsor will maintain regular contact with the investigative 
sites and monitor (e.g., central monitoring, on-site monitoring visits, and source data verification) 
on a regular basis to ensure compliance with this study protocol. Monitoring will be performed 
according to specific predefined monitoring Standard Operating Procedures (SOPs) and a study 
specific Monitoring Plan to ensure that the Investigator and his/her study team conduct the 
clinical investigation in accordance with the signed Clinical Trial Agreement, the CIP, any 
conditions imposed by the IRB, the Declaration of Helsinki, 21 CFR Parts 50, Good Clinical Practice 
according to ICH E6, and any other applicable regulations, to ensure adequate protection of the 
rights and safety of participants and the quality and integrity of the resulting data. Monitoring 
visits will be documented using monitoring visit reports. Rani Therapeutics must, therefore, be 
allowed access to the participant’s clinic and hospital records when so requested as per the 
participant informed consent document, Privacy Authorization, and CTA. 
The primary focus of the monitoring visits will be on the processes critical to protecting human 
participants, maintaining the integrity of study data, and compliance with applicable regulations. 
The findings will be used to correct investigator and site practices that could result in inadequate 
human participant protection and/or poor data quality. 
16.2 Access to Study Records 
The PI and site personnel must permit study-related monitoring, audits and IRB review by 
providing direct access to source documents. The PI should be available to the clinical study team 
to discuss the results of monitoring visits. Access to participant records (including hospital and 
clinic records) and regulatory documents must be granted to the Sponsor’s monitors.   
17 REQUIRED RECORDS AND REPORTS 
Investigators and Rani Therapeutics shall maintain records for this study for a period of at least 2 
years after the date on which the investigation is terminated or completed. An investigator may 
withdraw from the responsibility to maintain records for this period and transfer custody of the 
records to any other person who will accept responsibility for them.  
17.1 Investigator Records 
The investigator is responsible for the preparation and retention of the records cited below. All 
the below records, with the exception of case history records and electronic case report forms, 

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should be retained.  Electronic case report forms (eCRFs) may be maintained and signed 
electronically within the electronic data capture system during the study.   
• All correspondence between the IRB, Sponsor, another investigator, monitor and/or the 
investigator that pertains to the investigation, including required reports 
• Participant’s case history records, including, but not limited to: 
o Signed and dated informed consent form 
o Signed and dated privacy authorization form (may be combined with the informed 
consent form) 
o Observations of adverse events/adverse device effects 
o Medical history 
o Procedure and follow-up data 
o Documentation of the dates and rationale for any deviation from the protocol 
• Signed and dated eCRFs 
• Investigational CTM traceability records 
• All approved versions of the CIP and IB 
• Signed and dated CTA 
• Investigator’s current CV 
• Delegation of Authority Log 
• IRB study approval documentation, including written confirmation that the investigator 
or other study staff, if a member of the IRB, did not participate in the approval process 
17.2 Investigator Reports 
The investigator shall prepare and submit in a complete, accurate, and timely manner, the reports 
listed in Table 2. 
Table 2: Investigator Reporting Requirements 
Report 
Submit to: 
Description/Constraints 
Unanticipated Problems 
Sponsor 
Report to Sponsor ASAP, but no later than 72 hours after 
the investigator first learns of the effect 
IRB 
Report per the IRB policies and procedures 
Withdrawal of IRB approval 
Sponsor 
An investigator shall report to the sponsor, within 5 working 
days, a withdrawal of approval by the reviewing IRB 
Study CTM Related SAE  
 
Sponsor 
Report to Sponsor ASAP, but no later than 72 hours after 
the investigator first learns of the effect 
IRB 
Report per the IRB policies and procedures 
Deviations from the CIP 
Sponsor and IRB 
An investigator must notify the sponsor and IRB of any 
deviation from the CIP to protect the life or physical well-
being of a participant in an emergency.  Such notice shall be 
given ASAP, but no later than 5 working days after the 
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Report 
Submit to: 
Description/Constraints 
Failure to obtain informed 
consent prior to study CTM 
administration. 
Sponsor and IRB 
If an investigator uses study CTM without obtaining 
informed consent, the investigator shall report such use 
within 5 working days after device use 
Final report 
Sponsor 
This report must be submitted within three months of study 
completion or termination of the investigation or the 
investigator’s part of the investigation  
Progress 
Sponsor and IRB 
An investigator shall submit progress reports to the sponsor 
and IRB at regular intervals, but in no event less often than 
yearly 
Death 
Sponsor 
Within 10 days of knowledge of death 
17.3 Sponsor Records 
Rani Therapeutics will maintain the following accurate, complete, and current records relating to 
this investigation: 
• All correspondence with an investigator or an IRB, including required reports. 
• Records of shipment and disposition. Records of shipment shall include the name and 
address of the consignee, type, and quantity of device, date of shipment, and batch 
number or code mark. Records of disposition shall describe the batch number or code 
marks of any study CTM returned to Rani Therapeutics or disposed of in other ways by the 
investigator or another person, and the reasons for and method of disposal. 
• Signed financial disclosure information. 
• Records concerning adverse events. 
17.4 Sponsor Reports 
Sponsor reporting requirements are outlined in Table 3. 
Table 3: Sponsor Reporting Requirements 
Report 
Submit to: 
Description/Constraints 
Unanticipated 
Problems Evaluations 
All participating 
investigators 
10 working days after the sponsor first receives notice of 
the effect.  
Withdrawal of IRB 
approval 
All reviewing IRB, and 
participating investigators 
Within 5 working days after receipt of notice of the 
withdrawal of approval 
Progress Reports 
IRB and participating 
investigators 
At regular intervals, at least yearly 
Recall and device 
disposition 
All reviewing IRB and 
participating investigators 
Any request that an investigator return or otherwise 
dispose of any unit of a study CTM shall be reported 
within 30 working days after the request is made and 
shall state why the request was made 
Final Report 
All reviewing IRB and 
participating investigators 
Within 6 months of study termination 

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18 PUBLICATIONS 
Study results will be published following the final study analyses. The International Committee of 
Medical Journal Editors (ICMJE) authorship guidelines will be used.  The ICMJE guidelines require 
the conditions below are met to be included as an author: 
• Substantial contribution to conception and design, or acquisition of data, or analysis and 
interpretation of data 
• Drafting the article or revising it critically for important intellectual content 
• Final approval of the version to be published 
This study will be registered in www.clinicaltrials.gov, and results will be posted. 
19 REFERENCES 
1. Bouvy, JC., Cowie, L., Lovett, R., Morrison, D., Livingstone, H., Crabb, N., Use of patient 
preference studies in HTA decision making: A NICE perspective. The Patient-Patient-
Centered Outcomes Research. 2020;13,145-149. 
2. European Medicines Agency, 2017. Reflection paper on the pharmaceutical development 
of medicines for use in the older population, EMA/CHMP/QWP/292439/2017. 
3. Ternik, R., Liu, F., Bartlett, J., Khong, YM., Thiam Tan, DC., Dixit, T., Wang, S., Galella, EA., 
Gao, Z., Klein, S., Assessment of swallowability and palatability of oral dosage forms in 
children: Report from an M-CERSI pediatric formulation workshop. Int. J. of 
Pharmaceutics., 2018. 536; 570-581.