A Pilot Feasibility Study of Activated Charcoal in Healthy Adult Volunteers
Phase: EARLY_PHASE1
Conditions: Healthy Adult Volunteers
Sponsor: Masonic Cancer Center, University of Minnesota

Masonic Cancer Center 
University of Minnesota 
 
 
 
A pilot study of activated charcoal in healthy volunteers  
2019LS014 
IND 143937 
 
 
Principal Investigator: 
Armin Rashidi MD, PhD 
Division of Hematology, Oncology and Transplantation 
 
 
Co-Investigators: 
Alexander Khoruts, MD 
Pamala Jacobson, PharmD 
Christopher Staley, PhD* 
*non-clinical – will not consent subjects 
 
 
Biostatistician: 
Ryan Shanley, MS 
 
 
Version Date: 
October 18, 2019 
 
 
 
 
 
 
Confidential 
 
 

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Revision History 
 
Revision 
# 
Version 
Date 
Summary of Changes 
Consent 
Change 
n/a 
01/22/2019 Original submission to CPRC 
n/a 
 
03/29/2019 Changes based on IRB pre-review: 
• Added IND template language 
• Updated background section (added information on food 
grade AC, removed references to efficacy) 
• Updated to clarify that the AC used in this study is food 
grade 
• Added volunteer recruitment procedure 
• Added study withdrawal procedure 
Additional Changes: 
• Eligibility updated to add Relapsed AML 
• Clarified study dates for the volunteer stage (drink will be 
consumed on M/T/W for 3 weeks, not 9 consecutive days) in 
order to avoid weekend study visits 
• Minor edits to remove typos 
n/a 
 
06/25/2019 Upon advice of the FDA, this study will only test the charcoal 
in healthy volunteers – study resigned to single stage pilot 
study; study product will be medical grade AC; additional 
editsto inclusion/exclustion critier, study drug administration; 
study monitoring; study calendar as requested by FDA 
Yes 
 
10/18/2019 Typographical errors corrected 
No 
 
 
 
 
 
 
 
 
 
 
IND Sponsor/Principal Investigator Contact Information: 
Armin Rashidi, MD, PhD 
Hematology, Oncology and Transplantation 
Department of Medicine 
420 Delaware Street SE, MMC 480  
Minneapolis, MN  55455 
612-625-9604 (phone) 
612-625-6919 (fax) 
arashidi@umn.edu (email) 
 
 

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Table of Contents 
 
 
Abbreviations ............................................................................................................................... 6 
Protocol Synopsis ......................................................................................................................... 7 
Protocol Schema .......................................................................................................................... 8 
1 
Objectives ............................................................................................................................ 9 
1.1 
Primary Objective ........................................................................................................... 9 
1.2 
Secondary Objective ....................................................................................................... 9 
2 
Background and Rationale ...................................................................................................... 9 
2.1 
Infectious Complications in Chemotherapy........................................................................ 9 
2.2 
Prevention of Dysbiosis ................................................................................................... 9 
2.3 
Activated Charcoal ......................................................................................................... 9 
2.4 
Rationale ......................................................................................................................10 
3 
Study Design ........................................................................................................................10 
4 
Participant Selection .............................................................................................................10 
4.1 
Inclusion Criteria ...........................................................................................................10 
4.2 
Exclusion Criteria ...........................................................................................................11 
5 
Patient Registration ..............................................................................................................11 
5.1 
Participant Identification ................................................................................................11 
5.2 
Study Enrollment and Dose Level Assignment ...................................................................11 
5.3 
Participants Who Do Not Begin the Study ........................................................................11 
6 
Study Plan ...........................................................................................................................11 
6.1 
Healthy Volunteers ........................................................................................................11 
6.1.1 
Dose Assignment ....................................................................................................11 
6.1.2 
Consumption of Study Product (Oral AC) ...................................................................12 
6.1.3 
Experience Rating ...................................................................................................12 
6.1.4 
Compensation........................................................................................................12 
6.2 
Subject Monitoring ........................................................................................................13 
6.3 
Management of Selected Expected Toxicities ...................................................................13 
6.4 
Supportive Care ............................................................................................................13 
6.5 
Duration of Study Participation .......................................................................................13 

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6.6 
Withdrawal from Study ..................................................................................................13 
7 
Schedule of Activities ............................................................................................................14 
8 
Study Product Information ....................................................................................................14 
8.1 
Medical Grade Activated Charcoal ...................................................................................14 
8.1.1 
Other Names .........................................................................................................14 
8.1.2 
Description ............................................................................................................14 
8.1.3 
Mode of Action ......................................................................................................14 
8.1.4 
Availability .............................................................................................................14 
8.1.5 
Storage .................................................................................................................15 
8.1.6 
Preparation and Administration ...............................................................................15 
8.1.7 
Toxicities ...............................................................................................................15 
9 
Event Monitoring, Documentation and Reporting ....................................................................15 
9.1 
Event Terminology ........................................................................................................16 
9.2 
Event Documentation ....................................................................................................17 
9.3 
SAE and Death Documentation .......................................................................................17 
9.4 
Expedited Event Reporting .............................................................................................17 
10 
Study Data Collection and Monitoring .................................................................................18 
10.1 
Data Management.........................................................................................................18 
10.2 
Case Report Forms ........................................................................................................18 
10.3 
Data and Safety Monitoring Plan (DSMP) .........................................................................19 
10.4 
Study Monitoring ..........................................................................................................19 
10.5 
Record Retention ..........................................................................................................19 
11 
Study Endpoints ................................................................................................................20 
11.1 
Primary Endpoint ..........................................................................................................20 
11.2 
Secondary Endpoint .......................................................................................................20 
12 
Statistical Considerations ...................................................................................................20 
12.1 
Study Design .................................................................................................................20 
12.2 
Sample Size Considerations ............................................................................................20 
12.3 
Statistical Analysis .........................................................................................................20 
13 
Ethical and Regulatory Considerations .................................................................................21 
13.1 
Good Clinical Practice ....................................................................................................21 
13.2 
Ethical Considerations ....................................................................................................21 

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13.3 
Informed Consent .........................................................................................................21 
14 
References .......................................................................................................................21 
Appendix I - Eligibility Checklist .....................................................................................................22 
Appendix II – Volunteer Product Rating Form .................................................................................23 
 
 
 

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Abbreviations 
ABBREVIATION 
DEFINITION 
AC 
ACTIVATED CHARCOAL 
AE 
 
ADVERSE EVENT 
AHC 
ACADEMIC HEALTH CENTER 
CDI 
CLOSTRIDIUM DIFFICILE INFECTION 
CETI 
CANCER EXPERIMENTAL THERAPEUTICS INITIATIVE 
CFR 
CODE OF FEDERAL REGULATIONS 
CPRC 
CANCER PROTOCOL REVIEW COMMITTEE 
CRF 
CASE REPORT FORM 
CTCAE 
COMMON TOXICITY CRITERIA ADVERSE EVENT 
CTEP  
CANCER THERAPY EVALUATION PROGRAM 
CTO 
CLINICAL TRIALS OFFICE 
CTSI 
CLINICAL AND TRANSLATIONAL SCIENCE INSTITUTE 
DSMP 
DATA AND SAFETY MONITORING PLAN 
IRB 
INSTITUTIONAL REVIEW BOARD 
MCC 
MASONIC CANCER CENTER 
MCC-CISS 
MASONIC CANCER CENTER - CLINICAL INFORMATICS SHARES SERVICES 
NCI 
NATIONAL CANCER INSTITUTE 
ONCORE 
ONLINE ENTERPRISE RESEARCH MANAGEMENT ENVIRONMENT 
PHI 
PROTECTED HEALTH INFORMATION 
SAE 
SERIOUS ADVERSE EVENT 
SOP 
STANDARD OPERATING PROCEDURE 
 
 
 

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Protocol Synopsis 
Study Design: 
This is a pilot study designed to test feasibility, tolerability, and safety of medical grade 
oral Activated Charcoal (AC) in 12 healthy volunteers. 
Primary Objective: 
Compare 2 extemporaneously prepared AC suspensions at 2 doses (4 combinations in 
total) in healthy volunteers for palatability/tolerability 
Patient Population: 
Healthy adult volunteers 
Inclusion Criteria: 
• Age >18 years  
• No use of prescription medications, including oral birth control, currently or in the last 
30 days 
• Sexually active women must be using an effective form of contraception. 
Exclusion Criteria: 
• At risk of GI hemorrhage or perforation due to underlying pathology, recent surgery, 
or medical conditions that could be adversely affected by the administration of AC. 
• Planning to have an endoscopic procedure  
• Known hypersensitivity to AC 
• Non-English speakers  
Study Plan: 
In the proposed pilot study, we will compare 2 extemporaneously prepared AC 
suspensions at 2 doses (4 combinations in total) in healthy volunteers for 
palatability/tolerability. 
Study Product 
Medical Grade Activated Charcoal  
Enrollment Plan: 
12 healthy adults enrolled in a 4 month period  
 
 

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Protocol Schema 
 
 

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1 Objectives 
1.1 Primary Objective 
The primary objective is to compare 2 extemporaneously prepared Medical Grade Activated 
Charcoal, “AC” suspensions at 2 doses (4 combinations in total) in healthy volunteers for 
palatability/tolerability. 
1.2 Secondary Objective 
Determine the incidence of grade 2 and above SAEs deemed at least probably related to AC.  
2 Background and Rationale 
2.1 Infectious Complications in Chemotherapy 
Antibiotics disrupt gut microbial communities (dysbiosis). A large fraction of most antibiotics, 
even when administered intravenously, reaches the colonic lumen and its commensal flora. 
Antibiotics can reach the gut lumen via mechanisms that include incomplete absorption in 
the small bowel (e.g., macrolides)1, hepatic excretion via bile (e.g., tetracyclines)2, or active 
transfer across the intestinal mucosa into the gut lumen (e.g., fluoroquinolones)3.  
In the absence of antibiotics, a stable and diverse gut microbiota effectively inhibits 
colonization by potential pathogens. In the presence of antibiotics, however, pathogenic 
organisms can grow and cause intestinal and systemic infections. The best example for such 
infections is C. difficile infection (CDI). Even a single dose of an antibiotic (e.g. pre-operative 
single-dose intravenous antibiotic) can lead to CDI.  Surprisingly, no attempts have been made 
to prevent dysbiosis in individuals exposed to antibiotics. A novel strategy that protects the 
indigenous microbiota without detracting from the beneficial effects of antibiotics could 
prevent pathobiont outgrowth and reduce infectious complications of antibiotic use. 
2.2 Prevention of Dysbiosis 
It is important to discover ways to prevent the untoward consequences of dysbiosis in 
individuals exposed to antibiotics. The use of oral AC, a potent non-absorbable adsorbent, 
may protect the gut microbiota by adsorbing the fraction of intravenous (IV) antibiotics that 
ultimately reaches the intestinal lumen. 
2.3  Activated Charcoal 
Activated charcoal (AC) is a processed form of carbon with small, low-volume pores that 
increase the surface area available for adsorption. As a potent adsorbent with no systemic 
absorption from the gut, AC is a standard and effective agent used in the management of 
poisonings when gastrointestinal decontamination of drugs or chemicals is indicated. 

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2.4 Rationale 
Investigators are looking for new ways to protect the microbiome during the period of 
antibiotic exposure, improve the safety of antibiotics and reduce the rate of dysbiosis-related 
complications in patients. Determining the palatability and tolerability of AC in healthy 
volunteers in this research will aid in the design of future trials to investigate the efficacy of 
AC in patients. 
3 Study Design 
We will use the powder form of medical grade oral AC and mix it with liquids for 
administration. 12 healthy volunteers will be enrolled to determine the two most palatable 
and tolerable AC combinations. There will be a total of 4 combinations (2 AC doses and 2 
solutions) in stage 1. Each participant will drink an assigned combination every day for 3 
consecutive days (Monday, Tuesday, Wednesday, “M/T/W”) and switch to a different 
assigned combination M/T/W the following week. AC solution assignments will be defined 
before the study using a balanced incomplete block design.  Each subject will rate their 
experience using a 5-point scale every day for the 12 days they are on study.  
The following outcome variables will be measured: 
(i) 
Each healthy volunteer will rate their experience using a 5-point scale (1=terrible, 
2=bad, 3=okay, 4=good, 5=great) every day.    
(ii) 
To evaluate tolerability, after each round of study product consumption, a member 
of the study team will contact the subject and screen for grade 2 or higher AEs and 
SAEs 
4 Participant Selection 
Study entry is open to adult volunteers regardless of gender or ethnic background. While 
there will be every effort to seek out and include women and minorities, the subject 
population is expected to reflect the population of Minnesota. 
4.1 Inclusion Criteria  
• Age ≥18 years  
• No use of prescription medications, including oral birth control, currently or in the last 
30 days 
• Sexually active women must be using an effective form of contraception. Note that 
subjects who are on oral contraception should use an additional form of 
contraception such as barrier methods, as AC may interfere with the efficacy of oral 
contraceptive. 

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• Voluntary written consent signed before performance of any study-related 
procedure 
4.2 Exclusion Criteria 
• At risk of GI hemorrhage or perforation due to underlying pathology, recent surgery, 
or medical conditions that could be adversely affected by the administration of AC. 
• Planning to have an endoscopic procedure 
• Known hypersensitivity to AC 
• Non-English speakers 
5 Patient Registration 
Registration will occur after the participant has signed the subject consent and eligibility is 
confirmed, but before any study procedures have occurred. To be eligible for registration to 
this study, the participant must meet each criteria listed on the eligibility checklist (found in 
appendix I) based on the eligibility assessment documented in the participant’s research 
record.  
5.1 Participant Identification 
Healthy Volunteers will respond to poster advertisements containing a brief study 
description and the contact information of the study coordinator. 
5.2 Study Enrollment and Dose Level Assignment 
Upon completion of the screening evaluation, eligibility confirmation and obtaining 
written consent the Study Coordinator or designee will enroll the volunteer on study in 
OnCore. 
The Primary Clinical Research Coordinator (PCRC) or designee will assign the study dose-
solution and add the on-study date to complete enrollment. 
5.3 Participants Who Do Not Begin the Study  
If a participant is registered to the study, and is later found not able to begin the study, 
for any reason, the participant will be taken off study. The Study Coordinator or designee 
will update OnCore of the participant’s non-study status. The participant will be replaced 
to fulfill enrollment requirements. 
6 Study Plan 
6.1 Healthy Volunteers 
6.1.1 Dose Assignment 

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Dose assignments will be defined at the time of study registration using a balanced 
incomplete block design (Table 1).  
 
 
  
 
 
 
 
 
 
The dose levels are 12 and 25 of medical grade oral AC. While the standard AC dose for 
poison control is 25-100 grams, these smaller doses have been chosen to ensure safety.  
The AC will be mixed with 4 oz of either tap water or apple juice for a total of 4 
combinations.  
6.1.2 Consumption of Study Product (Oral AC) 
Participants will report to the University of Minnesota Health Clinical Research Unit 
(CRU) on a daily basis and consume the assigned combination of oral AC. Each 
participant will drink an assigned combination every day for 3 consecutive days 
(M/T/W) and switch to a different assigned combination for the 3 days (M/T/W) the 
following week. Subjects will drink AC in sitting position. Subjects must stay in the 
research unit for 15 minutes after consuming AC to be observed for aspiration. 
6.1.3 Experience Rating 
After drinking the solution, each subject will rate their experience using a 5-point scale 
(1=terrible, 2=bad, 3=okay, 4=good, 5=great) every day (Appendix III). They will be asked 
to do this daily starting day 1 (Mon of week 1) through day 12 (Friday of week 2).  
6.1.4 Compensation 
Each of the healthy volunteers participating this pilot study will receive an Amazon gift 
card for $50. 
  
  
Days 1-3 
(M,T, W – week 1) 
Days 8-10 
(M,T, W – week 2) 
Subject 
Solution 
Dose Solution 
Dose 
1 
A 
1 
B 
2 
2 
A 
2 
B 
1 
3 
B 
1 
A 
2 
4 
B 
2 
A 
1 
5 
A 
1 
B 
2 
6 
A 
2 
B 
1 
7 
B 
1 
A 
2 
8 
B 
2 
A 
1 
9 
A 
1 
B 
2 
10 
A 
2 
B 
1 
11 
B 
1 
A 
2 
12 
B 
2 
A 
1 

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6.2 Subject Monitoring 
Healthy volunteers will be observed for fifteen minutes after consuming the AC.  Upon 
leaving the research unit, they will have access to the CRA via phone. For 2 days after 
each round of study product consumption, a member of the study team will contact the 
subject and screen for all grade 2 or higher AEs and SAEs.  
Subjects with an adverse event will be followed until the event has resolved or stabilized 
with sequelae. 
6.3 Management of Selected Expected Toxicities 
Toxicity data is based on studies using pharmaceutical grade AC for treatment of 
intentional overdose/poison control. These doses are much higher than the planned 
doses of medical grade AC on this protocol. Lower doses are thought to be more 
tolerable. 
• The most common toxicity of AC (doses used for poisoning treatment) is 
nausea/vomiting, ranging from 15-27%. 
• Pulmonary aspiration is the most serious complication, occurring in <1% of 
patients. AC will not be administered to patients at risk for aspiration.  
It should be noted that the cause of aspiration is multifactorial, and part of the risk 
reported in studies should be contributed to the effect of toxin or the loss of protective 
reflexes in cases of poisoning. We do not expect these to be present in our participants. 
6.4 Supportive Care  
No specific supportive care is needed.  
6.5 Duration of Study Participation 
Participants will be involved for 12 days over a 2 week period including 6 days of active 
study participation and 4 days of study team follow-up.  
6.6 Withdrawal from Study 
Participants have the right to withdraw consent at any time by informing a member of 
the study staff or by following the instructions provided in the HIPAA document. 
 
 

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7 Schedule of Activities 
 
 
Screening 
Visit 
Week 1-2 
Consent and eligibility screening 
X 
 
Physical Exam 
X 
 
Drink Study product in either tap water, 
protein shake, or apple juice (per table 1*) 
 
M, T, W 
Rate Experience (taste test) 
 
M, T, W 
Screen for AEs 
 
M, T, W 
Telephone call from study staff to check for 
AEs 
 
Th, F 
8 Study Product Information 
8.1 Medical Grade Activated Charcoal 
8.1.1 Other Names 
Medical grade AC, “Activated Charcoal Powder, USP”, activated carbon. 
 
8.1.2 Description 
Activated Charcoal, Powder, USP is carbon that has been treated to create low-
volume pores that increase the area available for chemical reactions and 
adsorption. The most common pharmaceutical uses of activated charcoal is as a 
purification agent and antitoxin. All Spectrum Chemical USP products are 
manufactured, packaged and stored under current Good Manufacturing Practices 
(cGMP) per 21CFR part 211 in FDA registered and inspected facilities. 
 
8.1.3 Mode of Action 
Hemoperfusion through columns of activated charcoal to remove endogenous or 
exogenous toxins in uremia, hepatic failure, or acute toxicity associated with 
overdose of certain drugs. 
 
8.1.4 Availability  
Medical grade AC, “Activated Charcoal Powder, USP” will be purchased from 
Spectrum Chemical MFG Corporation. https://www.spectrumchemical.com 
Spectrum is an FDA registered manufacturer and distributor of chemicals and 
laboratory products.  
 

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8.1.5 Storage 
 As per the Spectrum Safety Data Sheet, the container of AC should be kept tightly 
closed in a dry and well-ventilated place. The container should be stored at room 
temperature. 
8.1.6 Preparation and Administration  
A member of the study team will make a suspension using 12g or 25g, or 50g of 
AC mixed with 4 oz. of either tap water or apple juice. The solutions will be 
administered as per section  
8.1.7 Toxicities 
GI Effects 
May cause vomiting, constipation, diarrhea, and GI obstruction or fecal impaction 
in dehydrated patients. 
Generally should not be used when decreased peristalsis present (reduced or 
absent bowel sounds); if risk of GI obstruction, perforation, or hemorrhage exists; 
if surgery has occurred recently; or if electrolyte imbalance or volume depletion 
exists. 
Pulmonary Effects 
Aspiration of activated charcoal may lead to more severe complications than 
aspiration of gastric contents alone. Aspiration from vomiting or misdirected 
nasogastric catheter has resulted in granulomatous reactions, bronchiolitis 
obliterans, tissue reaction to suspension agents (sorbitol, povidone), increased 
lung permeability, and rarely, death. 
Use of Fixed Combination 
When used in fixed combination with other agents, consider the cautions, 
precautions, and contraindications associated with the concomitant agents. 
Common Adverse Effects 
Vomiting, diarrhea, constipation, black stools. 
9 Event Monitoring, Documentation and Reporting 
Toxicity and adverse events will be classified and graded according to NCI's Common 
Terminology Criteria for Adverse Events version 5.0 (CTCAE V5) and reported on the schedule 

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below. A copy of the CTCAE can be downloaded from the CTEP home page.  
(http://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm#ctc_50). 
The following definitions of adverse events (AEs) and serious adverse events (SAEs) will 
determine whether the event requires expedited reporting via the SAE Report Form in 
addition to routine documentation in the OnCore AE case report form (CRF).  
Note:  throughout this section the generic term “study drug” refers to study product, medical 
grade Oral AC. 
9.1 
Event Terminology 
Adverse Event:  Any untoward medical occurrence associated with the use of a drug in 
humans, whether or not considered drug related. 
 
Serious Adverse Event:  An adverse event is considered “serious” if, in the view of either 
the investigator or sponsor, it results in any of the following outcomes:  
• Death 
• A life-threatening adverse experience 
• Inpatient hospitalization or prolongation of existing hospitalization 
• A persistent or significant incapacity or substantial disruption of the ability to conduct 
normal life functions 
• A congenital anomaly/birth defect 
• Important medical events that may not result in death, be life-threatening, or require 
hospitalization may be considered serious when, based upon appropriate medical 
judgment, they may jeopardize the patient or subject and may require medical or 
surgical intervention to prevent one of the outcomes listed in this definition.  
 
Unexpected Event: An adverse event or suspected adverse reaction is considered 
“unexpected” if it is not listed in protocol-related documents (e.g. protocol, consent 
documents, investigator brochure, package insert), or is not listed at the specificity or 
severity that has been observed or given the characteristics of the subject population 
being studied.   
 
Attribution: is the relationship between an adverse event or serious adverse event and 
the study drug. Attribution is assigned as follows: 
• Definite – The AE is clearly related to the study drug 
• Probable – The AE is likely related to the study drug 
• Possible – The AE may be related to the study drug 
• Unlikely – The AE is doubtfully related to the study drug 

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• Unrelated – The AE is clearly not related to the study drug 
Attribution must be assigned by the treating physician or the PI. 
 
The following definitions are from the Masonic Cancer Center’s Standard Operating 
Procedure (SOP) Deviation Reporting: 
 
Major Deviation: A deviation or violation that impacts the risks and benefits of the 
research; may impact subject safety, affect the integrity of research data and/or affect a 
subject’s willingness to participate in the research. Deviations that place a subject at risk, 
but do not result in harm are considered to be major deviations. 
 
Minor Deviation: A deviation or violation that does not impact subject safety, compromise 
the integrity of research data and/or affect a subject’s willingness to participate in the 
research. 
9.2 Event Documentation 
Participants will be monitored for adverse events from the 1st dose of study treatment 
through day 12. After that time point, events meeting the definition of serious and at 
least possibly related to study treatment will be documented upon knowledge. 
We will collect the following Grade 2-5 adverse events attributable to AC: 
• Aspiration of activated charcoal  
In addition any event meeting the definition of a serious adverse event (SAE) regardless 
of attribution that occurs during this period will be documented in the source document 
and recorded in OnCore. 
9.3 SAE and Death Documentation 
Any event meeting the definition of a serious adverse event (SAE) requires 
documentation using the MCC SAE Report Form in OnCore.  
9.4 
Expedited Event Reporting 
Agency 
reporting to 
Criteria for reporting 
Timeframe 
Form to Use 
Submission 
address/email 
address 
U of MN IRB  
Unanticipated death of a locally enrolled 
subject(s); New or increased risk; Any 
adverse event  that require a change to the 
protocol or consent form – refer to the IRB 
website for complete details  
5 Business 
Days 
IRB Report Form  
 
irb@umn.edu 

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10 Study Data Collection and Monitoring 
10.1 Data Management 
This study will collect regulatory and clinical data using University of Minnesota CTSI’s 
instance of OnCore® (Online Enterprise Research Management Environment). The Oncore 
database resides on dedicated secure and PHI compliant servers. All relevant AHC IS 
procedures related for PHI compliant servers (as required by the Center of Excellence for 
HIPAA Data) apply to Oncore databases. 
The data will be integrated and extracted to researchers through the CTSI Informatics 
team and will be delivered through secure and compliant mechanisms (e.g. AHC IE data 
shelter, BOX, sftp, etc). If data de-identification is needed, then compliant AHC IE data de-
identification tools will be used. The informatics team will grant the IRB approved study 
team members access to data. 
Key study personnel are trained on the use of OnCore and will comply with protocol 
specific instructions embedded within the OnCore. 
10.2 Case Report Forms 
Participant data will be collected using protocol specific electronic case report forms (e-
CRF) developed within OnCore based on its library of standardized forms. The e-CRF will 
be approved by the study’s Principal Investigator and the Biostatistician prior to release 
for use. The Primary Clinical Research Coordinator or designee will be responsible for 
registering the patient into OnCore at time of study entry, completing e-CRF based on the 
patient specific calendar, and updating the patient record until patient death or end of 
required study participation.  
Clinical deviations per current IRB reporting requirements 
OnCore 
Deviation Form  
Masonic 
Cancer Center 
SAE 
Coordinator 
Events that meet the definition of dose 
limiting toxicity or an early study stopping 
rule 
At time of 
reporting 
Event Form 
mccsaes@umn.edu 
FDA 
Unexpected and fatal or unexpected and life 
threatening suspected adverse reaction 
no later than 
7 Calendar 
Days 
MCC SAE Report 
Form 
Submit to FDA as 
an amendment to 
IND  
 
1) Serious and unexpected suspected 
adverse reaction or 
2)  increased occurrence of serious suspected 
adverse reactions over that listed in the 
protocol or investigator 
brochure or 
3) findings from other sources (other studies, 
animal or in vitro testing) 
no later than 
15 Calendar-
Days 

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10.3 Data and Safety Monitoring Plan (DSMP) 
The study’s Data and Safety Monitoring Plan will be in compliance with the University of 
Minnesota Masonic Cancer Center's Data & Safety Monitoring Plan (DSMP), which can be 
accessed at http://z.umn.edu/dmsp. 
 
For the purposes of data and safety monitoring, this study is classified as high risk. 
Therefore the following requirements will be fulfilled: 
 
 At least quarterly review of the study’s progress by the Masonic Cancer Center Data 
and Safety Monitoring Council (DSMC). 
 The PI will comply with at least twice yearly monitoring of the project by the Masonic 
Cancer Center monitoring services. 
 The PI will oversee the submission of all reportable adverse events per section 9.3 to 
the Masonic Cancer Center’s SAE Coordinator, the University of Minnesota IRB, and 
the FDA.  
 
In addition, at the time of the continuing review with the University of Minnesota IRB, a 
copy of the report with any attachments will be submitted to the Cancer Protocol Review 
Committee (CPRC). 
 
IND Annual Reports 
In accordance with regulation 21 CFR § 312.33, the Sponsor-Investigator will submit a 
progress report annually. The report will be submitted within 60 days of the anniversary 
date that the IND went into effect.  
10.4 Study Monitoring  
The investigator will permit study-related monitoring, audits, and inspections by the 
study’s Principal Investigator and/or any designees, the local IRB, government regulatory 
bodies, and University of Minnesota compliance groups. The investigator will make 
available all study related documents (e.g. source documents, regulatory documents, 
data collection instruments, study data, etc.). The investigator will ensure the capability 
for inspections of applicable study-related facilities (e.g. pharmacy, diagnostic laboratory, 
etc.) will be available for trial related monitoring, audits, or regulatory inspections. 
10.5 Record Retention 
The investigator will retain study records including source data, copies of case report form, 
consent forms, HIPAA authorizations, and all study correspondence in a secured facility for 
at least 6 years after the study file is closed with the IRB and FDA.  

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11 Study Endpoints 
11.1 Primary Endpoint 
The primary endpoint is the average palatability rating (on a 1-5 scale) of each treatment 
combination. 
11.2 Secondary Endpoint 
Safety, defined by the incidence of grade 2 and above AEs deemed at least probably related 
to AC by day 12. 
12 Statistical Considerations 
12.1 Study Design 
This is a pilot study designed to test tolerability and safety of oral AC in 12 healthy 
volunteers. 
 
We will follow a predetermined treatment assignment using the balanced 
incomplete block design shown in Section 6.1.1.  Twelve healthy subjects will be 
assigned two dose and solution combinations to take for three days each.  Each 
subject will receive each dose once and each solution once.  Different subjects 
will receive different combinations or different sequences.  Each of the four 
combinations will be given to six subjects total, allowing straightforward 
comparisons.  Each solution (or dose) precedes each of the others for exactly half 
of the subjects, to minimize confounding due to the ordering of the treatment 
assignments.  
12.2 Sample Size Considerations 
The sample size was chosen so that each combination could be given the same 
number of times.   
12.3 Statistical Analysis 
We will average each subject’s score over the 3 days of each treatment. If a 
subject misses one or more days, we will impute the average of the known days 
for the unknown days. We will also record the reported reason for not taking AC, 
and based on that we may adjust the imputation procedure on a case-by-case 
basis. Since the goal is to pick the most tolerable/palatable combination, we will 
choose the one with the highest average score; no statistical hypothesis tests are 
required. We will also consider the combination with the fewest percentage of 

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“terrible” or “bad” ratings, although this is expected to be associated with 
average score.   
13 Ethical and Regulatory Considerations 
13.1 Good Clinical Practice 
The study will be conducted in accordance with the appropriate regulatory 
requirement(s). Essential clinical documents will be maintained to demonstrate the 
validity of the study and the integrity of the data collected. Master files should be 
established at the beginning of the study, maintained for the duration of the study and 
retained according to the appropriate regulations.  
13.2 Ethical Considerations 
The study will be conducted in accordance with ethical principles founded in the 
Declaration of Helsinki. The IRB will review all appropriate study documentation in order 
to safeguard the rights, safety and well-being of the patients. The study will only be 
conducted at sites where IRB approval has been obtained. The protocol, informed 
consent, written information given to the patients, safety updates, annual progress 
reports, and any revisions to these documents will be provided to the IRB by the 
investigator.  
13.3 Informed Consent 
All potential study participants will be given a copy of the IRB-approved Consent to 
review. The investigator or designee will explain all aspects of the study in lay language 
and answer all questions regarding the study. If the participant decides to participate in 
the study, he/she will be asked to sign and date the Consent document. Patients who 
refuse to participate or who withdraw from the study will be treated without prejudice. 
14 References 
 
1. 
Nord, C. E. & Edlund, C. Impact of antimicrobial agents on human intestinal microflora. J. 
Chemother. 2, 218–37 (1990). 
2. 
Agwuh, K. N. & MacGowan, A. Pharmacokinetics and pharmacodynamics of the 
tetracyclines including glycylcyclines. J. Antimicrob. Chemother. 58, 256–265 (2006). 
3. 
Lowes, S. & Simmons, N. L. Multiple pathways for fluoroquinolone secretion by human 
intestinal epithelial (Caco-2) cells. Br. J. Pharmacol. 135, 1263–75 (2002). 
 
 

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Appendix I - Eligibility Checklist  
A pilot study of activated charcoal in healthy volunteers 
Eligibility Checklist – page 1 of 1 
Participant ID   19014-UMN-____ (assigned in OnCore) 
 
INCLUSION CRITERIA  
 
A “NO” response to any of the following disqualifies the participant from study entry. 
 
EXCLUSION CRITERION 
A “YES” response to the following disqualifies the participant from study entry. 
 
 
Yes      No 
1 
At risk of GI hemorrhage or perforation due to underlying pathology, recent 
surgery, or medical conditions that could be adversely affected by the 
administration of AC. 
 
 
2. 
Planning to have an endoscopic procedure 
 
 
3. 
Known hypersensitivity to AC 
 
 
4. 
Non-English speakers 
 
 
 
Date consent form signed: 
 
 
 
 
 
Having obtained consent and reviewed each of the inclusion/exclusion criteria, I verify that this 
participant is eligible. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Signature of person verifying eligibility  
 
 
 
 
Date 
 
 
 
 
Yes      No 
1 
Age ≥18 years 
 
 
2 
No use of prescription medications, including oral birth control, currently or in the last 
30 days 
 
 
3 
Sexually active women must be using an effective form of contraception. Note that 
subjects who are on oral contraception should use an additional form of contraception 
such as barrier methods, as AC may interfere with the efficacy of oral contraceptive. 
 
 
4 
Voluntary written consent signed before performance of any study-related procedure 
 
 

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Appendix II – Volunteer Product Rating Form 
 
Study ID: _____________________________ 
Date: ________________________ 
1. Please rate your charcoal experience today by choosing one the 5 items below 
 
 
2. Have you had any issues since last drink of charcoal that you think may be related to 
your charcoal experience? 
 
______________________________________________________________ 
 
______________________________________________________________ 
 
______________________________________________________________