The Efficacy and Tolerability of Canagliflozin in Healthy Individuals Comparing Dosing Protocols of Canagliflozin for Use as a Gerotherapeutic
Phase: PHASE4
Conditions: Healthy Aging
Sponsor: AgelessRx

 
Protocol Number: ALRx008 
 
                    Approval Date: Jan. 24, 2024 
Approval Number: IRCM-2024-384             
 
Continuing Review Date: Jan. 8, 2025 
 
IRCM-2024-384 
Jan. 24, 2024 
 
Title: The Efficacy and Tolerability of Canagliflozin in Healthy Individuals 
Comparing Dosing Protocols of Canagliflozin for use as a Gerotherapeutic 
 
Protocol Number: 
ALRx008 
 
Test Drug: Canagliflozin, also known as Invokana. 
 
Indication: For use in healthy, non-diabetic individuals (ages 18-85). 
 
Study Design: Prospective, non-randomized trial to evaluate tolerability and efficacy in reducing baseline glucose and 
glucose spikes in non-diabetic individuals. 
 
Site: This is a decentralized trial. Participants can be located in any of the 50 states of the USA. All participation will be via 
telemedicine using the AgelessRx website (agelessrx.com). 
 
Sponsor Name, Address, and Telephone Number: 
AgelessRx 
Address: 2370 E Stadium Blvd #2049 Ann Arbor, MI 48104 
Tel: (650) 503-9990 
Fax: (650) 729-0869 
Email: info@agelessrx.com 
Research Coordinator 
Andy Nyquist 
Address: 2370 E Stadium Blvd #2049 Ann Arbor, MI 48104 
Tel: (650) 272-3169 
Email: research@agelessrx.com 
Principal Investigator 
Sajad Zalzala, MD 
Address: 835 Mason St, Ste A250, Dearborn, MI 48126 
Tel: (313) 355-8657 
Fax: (888) 655-7536 
Email: doctor@agelessrx.com 
Institutional Review Board of the Institute of Regenerative and Cellular Medicine 
James P. Faber 
Tel: (786) 271-2156 
Email: jpfaber@ircm.org 
 
Compliance: 
The study will be conducted in accordance with standards of Good Clinical Practice, as defined by the International 
Conference on Harmonisation and all applicable federal and local regulations. 
 
Date of Protocol: January 16th, 2023 
 
Confidential Information 
The information contained within this protocol is confidential and may not be used, divulged, published, or otherwise 
disclosed without the prior written consent of AgelessRx. 

2 
Protocol Number: ALRx008 
 
                    Approval Date: Jan. 24, 2024 
Approval Number: IRCM-2024-384             
 
Continuing Review Date: Jan. 8, 2025 
 
 
1. Signature Page 
I have read this clinical protocol and confirm that to the best of my knowledge it accurately describes the design and conduct 
of the study titled “The Efficacy and Tolerability of Canagliflozin in Healthy Individuals: Comparing Dosing Protocols of 
Canagliflozin for use as a Gerotherapeutic”. 
 
 
 
 
 
Sajad Zalzala, MD 
Date 01/17/2024 

3 
Protocol Number: ALRx008 
 
                    Approval Date: Jan. 24, 2024 
Approval Number: IRCM-2024-384             
 
Continuing Review Date: Jan. 8, 2025 
2. Synopsis 
Name of Sponsor/Company: AgelessRx 
Name of product: Canagliflozin (trade names: Invokana) 
Title of study: The Efficacy and Tolerability of Canagliflozin in Healthy Individuals 
Comparing Dosing Protocols of Canagliflozin for use as a Gerotherapeutic 
Objectives: 
Primary: To measure the effects that canagliflozin intervention has on reducing average 
glucose in healthy individuals. 
 
Secondary: To assess the tolerability and side effects and urinary glucose excretion following 
the pulsatile dosing protocol. 
Methodology: 
1. 
Candidates will be offered participation through word of mouth and AgelessRx 
platform. 
2. 
Once screened and enrolled, participants will be randomized into one of two 
arms (A and B) and provided with all items included in the materials list below. 
3. 
Arms A & B: 
a 
Day 0: Participants will attach a continuous glucose monitor (CGM) 
and follow instructions for calibration period. 
b 
Day 1 – 14: Participants will take morning blood pressure readings, 
and keep dietary intake journal via Lifesum. 
c 
Day 7: Participant completes Urine Collection Kit #1 
4. 
Arm A: 
a 
Day 8 - 14: Participants take 100mg Invokana (canagliflozin) with first 
meal daily. 
b 
Day 15: 24h after final dose, Participant completes Urine Collection 
Kit #2 
c 
Day 16: 48h after final dose, Participant completes Urine Collection 
Kit #3 
d 
Day 17: 72h after final dose, Participant completes Urine Collection 
Kit #4 
5. 
Arm B: 
a 
Day 8 - 14: Participants take 150mg Invokana (canagliflozin) with first 
meal daily, every other day for a total of 4 doses. 
b 
Day 15: 24h after final dose, Participant completes Urine Collection 
Kit #2 
c 
Day 16: 48h after final dose, Participant completes Urine Collection 
Kit #3 
d 
Day 17: 72h after final dose, Participant completes Urine Collection 
Kit #4 
Number of subjects planned: Up to 20 healthy individuals via telehealth administration, 10 
individuals in each Arm. 

4 
Protocol Number: ALRx008 
 
                    Approval Date: Jan. 24, 2024 
Approval Number: IRCM-2024-384             
 
Continuing Review Date: Jan. 8, 2025 
 
Diagnosis and main criteria for inclusion: Subjects will be healthy and of any sex, any 
ethnicity, and any age from 18-85. Participants must be approved by AgelessRx Medical Team 
for use of canagliflozin. They also require a CGM-compatible mobile device (defined here) 
Test product, dose, and mode of administration (proposed): The tablets will be from the 
brand Invokana and have a dosage of 100 mg or 300 mg per tablet. Investigational drugs are 
to be administered orally. Investigational drugs will be provided by Curexa Pharmacy, 3007 
Ocean Heights Avenue, Egg Harbor Township, NJ 08234 
Duration of treatment: 7 days 
Criteria for evaluation: 
Efficacy: 
● 
CGM data 
● 
Urinary glucose 
Safety: 
● 
Tolerability 
● 
Adverse events 
● 
Blood pressure 
Statistical analysis: Demographic and baseline characteristics will be summarized using 
descriptive statistics. CGM readings will be analyzed using analysis of variance. Evaluation 
will be performed by research coordinators/MDs. 

5 
Protocol Number: ALRx008 
 
                    Approval Date: Jan. 24, 2024 
Approval Number: IRCM-2024-384             
 
Continuing Review Date: Jan. 8, 2025 
3. Study Design 
 

6 
Protocol Number: ALRx008 
 
                    Approval Date: Jan. 24, 2024 
Approval Number: IRCM-2024-384             
 
Continuing Review Date: Jan. 8, 2025 
 
 
 
Table of Contents 
1. Signature Page 
2 
2. Synopsis 
3 - 4 
3. Study Design 5 
4. Table of Contents 
6 - 7 
5. List of Abbreviations 
7 
6. Background and Rationale 
8 
6.1. Glucose Spikes 
8 
6.2. Canagliflozin 
8 
6.3. Current standard of care and alternative treatments for reduction of glucose spikes  9 
6.4. Rationale and Hypothesis 
9 
7. Objectives 
9 - 10 
7.1. Primary Objective 
9 
7.2. Secondary Objective 10 
8. Experimental plan 
10 
8.1. Study Design 
10 
8.2. Cost of Participation 10 
8.3. Number of Centers and Subjects 
10 
8.4. Estimated Study Duration 
10 
9. Subject Selection 
10 
9.1. Number of Subjects 10 
9.2. Inclusion Criteria 
10 
9.3. Exclusion Criteria 
11 
9.4. Withdrawal 11 
10. Schedule of Assessments and Procedures 
11 
10.0. Patient Recruitment 11 
10.1. Screening 
11 
10.2. Enrollment 11 
10.3. Safety and efficacy evaluations 
11 
11. Investigational Product 12 

7 
Protocol Number: ALRx008 
 
                    Approval Date: Jan. 24, 2024 
Approval Number: IRCM-2024-384             
 
Continuing Review Date: Jan. 8, 2025 
11.1. Investigational Drug 12 
11.2. Control Drug 
12 
11.3. Dosing and Administration 
12 
11.3.1. Dose Escalation, Dose Adjustments, Stopping Rules 
12 
11.3.2. Packaging and Labelling 
12 
11.3.3. Storage 
12 
11.3.4. Accountability 
12 
11.4. Concomitant Medications 
12 
12. Adverse Event Reporting 
12 
12.1. Adverse Events Definitions 
13 
12.2. Serious Adverse Events 
13 
12.3. Reporting of Adverse Events 13 
12.3.1. Routine 
13 
12.3.2. Expedited 13 
13. Statistical Analysis 
13 
14. Ethics 
14 
14.1. Ethical Conduct of the Study 
14 
 
14.2. Participant Information and Consent 
14 
 
14.3. Study Participant Confidentiality 
14 
15. Administrative Procedures 
14 
 
15.1. Modifications to the Protocol  14 
 
15.2. Plans for Dissemination of Findings 
14 
16. Reference List 
15 
 
Appendix 
 
16 
Appendix A 
 
16 
Appendix E 
 
18 
 
5. List of Abbreviations 
Abbreviation 
Definition 
ADR 
Adverse Drug Reaction 
AE 
Adverse event 
SAE 
Serious Adverse event 
CGM 
Continuous Glucose Monitor 

8 
Protocol Number: ALRx008 
 
                    Approval Date: Jan. 24, 2024 
Approval Number: IRCM-2024-384             
 
Continuing Review Date: Jan. 8, 2025 
6. Background and Rationale 
 
 
6.1 Glucose Spikes 
Excessive refined carbohydrate intake can lead to an excess of glucose in the blood. The pancreas works to stabilize blood 
sugar levels by secreting a surge of insulin to help move glucose into our cells or storage. However, even after excess 
glucose has been cleared, our insulin levels remain high. This leads to an overcorrection and subsequent low blood sugar. 
Unstable blood sugar is linked to depressed and anxious mood, “brain fog,” impaired cognitive performance, disturbed 
sleep, chronic pain, and poor workout performance. Conversely, stable blood sugar can boost our energy levels, mood, 
productivity, and overall well-being.2 
 
Glucose variability is not only a problem for individuals with diagnosed health conditions relating to glucose. According to a 
2018 study, “16 out of 20 participants who were classified as normal on standard clinical tests experienced severe post-meal 
glucose spikes that reached into the prediabetic range 15 percent of the time”3. Additionally, a 2009 study of glucose spikes 
studied more than 15,000 healthy, non-diabetic individuals. It found that elevated 2-hour postprandial glucose increased the 
risk of cardiovascular and all-cause death significantly4. 
 
Excessive post-meal blood glucose spikes are an independent risk factor for a host of chronic conditions, including diabetes, 
cardiovascular disease, stroke, kidney failure, cancer, retina damage, and cognitive decline. Eating to promote stable blood 
sugar and developing metabolic flexibility is critical to supporting your long-term health and wellbeing5. 
 
 
6.2 Canagliflozin 
Canagliflozin is an SGLT2 inhibitor. It is a compound also known under the name Invokana. Canagliflozin is used 
(with diet and other medications) to treat type 2 diabetes (a condition in which the body does not use insulin normally 
and therefore cannot control the amount of sugar in the blood). Canagliflozin works by blocking SGLT2, a protein that 
helps the body reabsorb glucose from urine to the bloodstream. The body instead excretes glucose through urine. 1 
 
 
Clinical studies 
Canagliflozin Tablets were studied as monotherapy and as combination therapy to metformin, insulin, or other 
treatments. The treatment effects on HbA1c levels and one-hour postprandial glucose levels are summarized for four 
placebo-controlled, double-blind, randomized studies conducted in the United States. The placebo-subtracted 
treatment differences, which are summarized below, were statistically significant for both variables in all of these 
studies. 
 
Study 1: (n=584) This study showed that canagliflozin caused a significant reduction in blood sugar soon after taking 
canagliflozin. This was true at both doses of 100 mg canagliflozin as well as with 300 mg of canagliflozin. Hba1c 
levels dropped by 0.8 mg/dl with the 100 mg treatment and by 1.0 mg/dl with the 300 mg treatment. 1 
 
Study 2: (n=20) Canagliflozin reduced postprandial plasma glucose by 35% and insulin excursions by 43% in this 
study (P < 0.001 for both). It also increased urinary glucose excretion (UGE0–6h, 18.2 ± 5.6 vs. <0.2 g; P < 0.001). It 
reduced blood glucose by increasing glucose excretion. 6 
 
Study 3: (n=1450) Canagliflozin at 100 mg and 300 mg reduced A1c levels by −0.65% and −0.74%, respectively, over 
a treatment period of 104 weeks. Also, it reduced systolic blood pressure by -2.0 mmHg with the 100 mg dose and by 
-3.1 mmHg with the 300 mg dose. 7 

9 
Protocol Number: ALRx008 
 
                    Approval Date: Jan. 24, 2024 
Approval Number: IRCM-2024-384             
 
Continuing Review Date: Jan. 8, 2025 
Study 4: (n=4401) Canagliflozin was generally well tolerated8. Adverse events related to the kidneys were lower with 
canagliflozin treatment of 100 mg, with an incidence of 60.2 per 1,000 vs an rate of 84.0 per 1,000 of the control 
group. 9 
 
 
6.3 Current standard of care and alternative treatments for glucose spikes 
Current standard of care for glucose control in diabetics revolves around the use of diet, and exercise, in combination 
with different medicines and molecules, such as Metformin, Insulin, Sulfonylureas, SGLT-2 inhibitors, and acarbose. 
In healthy, non-diabetic individuals, the main way to mitigate blood sugar spikes is to rely on diet and exercise. 
Non-diabetic individuals have to find ways to substitute sugars or carbohydrates from their diet to prevent spikes. 
Similarly, they exercise in order to have normally-functioning glucose disposal, or stay well hydrated by drinking water 
after consuming starchy meals.10 Glucose spikes often go untreated, and are common in healthy, non-diabetic 
individuals after high carbohydrate intake. 
 
6.4 Rationale and Hypothesis 
 
Canagliflozin is a prime candidate to reduce glucose spikes and blood sugar. It has consistently acted to treat type 2 
diabetes and has been shown to improve biomarkers such as fasted glucose and glucose spikes. 
 
The current FDA-approved use of the drug is for use together with diet and exercise to treat type 2 diabetes. Canagliflozin is 
sometimes used in combination with insulin or other diabetes medications taken orally. It is routinely prescribed at equal or 
higher doses than the ones proposed in this trial. 
 
AgelessRx Trial doses: 
100 mg and 150 mg doses, taken every day and every-other day, respectively. 
 
FDA-approved dose: 
Maximum recommended dose: 300 mg once daily. 
 
Some possible side effects at the FDA-approved doses include hypoglycemia, indigestion, nausea, UTI, increased urination 
or thirst, hypotension, ketoacidosis, dehydration, and headache. The doses we propose have potential for some side effects, 
though the drug is generally well tolerated. 
 
This trial will use a lower dose than the maximum one recommended by the FDA. We are using a maximum of 150 mg in 
one day vs the maximum of 300 mg each day recommended by the FDA. At this smaller dose, side effects are less 
common8. This dose has been shown to be generally safe. 
 
Our hypothesis is three-fold: 
1. 
Canagliflozin can be used safely and is well tolerated at doses of 100 mg per day or 150 mg every two days in 
healthy, non-diabetic individuals. 
 
2. 
Usage of canagliflozin at these doses can effectively reduce glucose spikes (and their detrimental effects) and 
blood sugar levels measured by CGM in a healthy population. 
 
3. 
Usage on alternate days will be effective as measured by our endpoints. 
 
7. Objectives 
 
7.1 Primary Objective 
To measure the effects that Canagliflozin intervention has on blood glucose at the tested doses. This will be measured by 
observing glucose spikes following a high-carbohydrate meal at the tested doses, as well as by studying baseline glucose 
levels with and without canagliflozin. 

10 
Protocol Number: ALRx008 
 
                    Approval Date: Jan. 24, 2024 
Approval Number: IRCM-2024-384             
 
Continuing Review Date: Jan. 8, 2025 
7.2 Secondary Objective 
To assess the tolerability and side effects of the dosing protocol, and measure urinary glucose excretion. 
 
 
 
8 Experimental plan 
 
8.1 Study Design 
This study is designed to mitigate the effects of glucose with intermittent oral Canagliflozin for healthy, non-diabetic 
volunteers of any sex who enroll in the study. The volunteers can be within 18-85 years of age at the time of enrollment. 
Participants will provide informed consent via AgelessRx EMR. If eligible, prescriptions will be provided online through the 
AgelessRx website (www.agelessrx.com). Participants will be randomized into two arms: Arm A will take 100 mg of 
canagliflozin each day for a total of 7 doses, while Arm B will take 150 mg of canagliflozin every other day for a total of 4 
doses. Participants in Arm B will also be provided a pill cutter to use throughout the trial on the 300mg tablet. 
All participants will begin the trial on the day that they apply a continuous glucose monitor (considered Day 0) and will be 
asked to take daily blood pressure reading. After one week of baseline readings, both arms will start their canagliflozin 
dosing protocols. 
Participants will be asked to complete 7 total surveys to outline side effects and tolerability, one each day starting after their 
canagliflozin consumption. 
Participants will be asked to complete a dietary intake journal through Day 0 – Day 14. Lifesum (https://lifesum.com/) should 
be used to track Carbohydrate/Protein/Fat consumption. Participants will share their dietary intake journal twice over their 
participation (Day 7 & Day 14). 
 
 
8.2 Cost of Participation 
This trial will be sponsored under the organization AgelessRx. There will be no cost to the participant to participate. 
 
8.3 Number of Centers and Subjects 
We will recruit up to 20 healthy participants to participate in the study. Online prescriptions will be provided by Dr. Sajad 
Zalzala via the AgelessRx website (www.agelessrx.com). Our partner pharmacy with the ability to ship to most states 
nationwide will provide the prescriptions and CGMs to participants. Efficacy testing will be performed by AgelessRx. To 
measure glucose, the Abbott Laboratories Freestyle Libre CGM (https://www.freestyleprovider.abbott/us-en/freestyle-libre- 
2.html) will be used. For urinalysis, Access Medical Labs Glucose, Urine (https://www.rupahealth.com/lab-tests/access- 
medical-labs-glucose-random-urine#description) will be used. 
 
8.4 Estimated Study Duration 
We anticipate the study will last a maximum of 90 days. 
 
9 Subject Selection 
 
9.1 Number of Subjects 
Up to 20 individuals 
 
9.2 Inclusion Criteria 
1. 
Age 18-85 
2. 
Any sex 
3. 
Any ethnicity 
4. 
Interest in taking Canagliflozin 
5. 
Approved by the AgelessRx Medical team to take Canagliflozin 
6. 
Willing and technically able to use and operate a CGM 
7. 
Own a CGM-compatible phone 

11 
Protocol Number: ALRx008 
 
                    Approval Date: Jan. 24, 2024 
Approval Number: IRCM-2024-384             
 
Continuing Review Date: Jan. 8, 2025 
8. 
Relatively good health with only well-managed chronic diseases (hypertension, coronary artery disease, 
type II diabetes, etc.) clinically stable 
9. 
Adequate cognitive function to be able to give informed consent 
 
 
 
9.3 Exclusion Criteria 
1. 
Diabetes of any type 
2. 
Taking metformin or any other glucose lowering medication 
3. 
Other diabetes medication 
4. 
Active malignancy of any kind 
5. 
Clinically relevant renal or kidney disease or dysfunction 
6. 
History of eating disorder 
7. 
Any diuretic 
7. 
 Taking any medication, or has any medical condition, that might interfere with the action of canagliflozin or the 
CGM sensor 
 
9.4 Withdrawal 
 
Participants are free to withdraw from the study at any time. They can do so by notifying the Principal Investigator through 
email or phone call. Participants can provide consent whether or not to allow use of data obtained up to that moment. 
 
10 Schedule of Assessments and Procedures 
10.0 Patient Recruitment 
Candidates will be offered the opportunity to participate in this interventional trial after approval of canagliflozin through the 
AgelessRx platform and expressing interest via screening questionnaire. 
 
10.1 Screening 
Candidates will be offered the opportunity to participate in this trial after approval of canagliflozin prescription through the 
AgelessRx platform. Patients must proceed through medical intake, consent to participate, consultation with the AgelessRx 
medical team (synchronously or asynchronously, depending on the regulations of the state in which the candidate resides), 
and approval before receiving their treatment. Medical intake will be reviewed by the AgelessRx medical team and consent 
responses will be reviewed by the research coordinator. Once the candidate has been approved for their canagliflozin 
prescription and the patient has expressed interest and consented to participation, the AgelessRx research coordinator will 
contact the candidate for additional instruction. The medical intake and consent built into the patient process will include 
inclusion/exclusion screening criteria and will serve as a screening tool for medical and research personnel. The consent 
language built into the patient intake workflow can be found in Appendix A. Identity validation will occur prior to product 
intake submission and will be verified following consent completion, as a photo of self and I.D. are required before the 
patient may proceed. Informed consent will be captured via free text name entry within the consent questionnaire. 
 
10.2 Enrollment 
Participants will be enrolled in the study for a total of two weeks. After the two weeks, participants will be free to use the trial 
drug off-label as they choose. 
 
 
10.3 Safety and efficacy evaluations 
 
The primary endpoint, average glucose, will be assessed by examining blood glucose (mg/dL) area under curve as 
measured by CGM. Glucose data on days without canagliflozin treatment will serve as a control. 

12 
Protocol Number: ALRx008 
 
                    Approval Date: Jan. 24, 2024 
Approval Number: IRCM-2024-384             
 
Continuing Review Date: Jan. 8, 2025 
The secondary endpoints of safety and tolerability and urinary glucose excretion will also be assessed. Safety and 
tolerability will be measured by adverse event reporting, blood pressure monitoring, and by comparing treatment tolerability 
survey results with control tolerability results through subjective surveys. Urinary glucose excretion will be measured by at- 
home glucose testing strips. 
 
 
11 Investigational Product 
 
11.1 Investigational Drug 
Canagliflozin is an SGLT2 inhibitor. It is known under the name Invokana, when mixed with other compounds. It is 
chemically known as (2S,3R,4R,5S,6R)-2-[3-[[5-(4-fluorophenyl)thiophen-2-yl]methyl] 
-4-methylphenyl]-6-(hydroxymethyl)oxane-3,4,5-triol. It has a molecular weight of 444.52 g/mol and is an off-white 
powder. It is used to treat type 2 diabetes mellitus (a condition in which the body does not use insulin normally and 
therefore cannot control the amount of sugar in the blood). It works by inhibiting a sodium-glucose pump in the 
kidneys, SGLT2, leading to increased glucose excretion through urine. This helps reduce blood glucose levels as 
glucose is not reabsorbed into the blood. 
 
11.2 Control Drug 
No placebo will be used in this trial. 
 
11.3 Dosing and Administration 
 
11.3.1 Dose Escalation, Dose Adjustments, Stopping Rules 
Participants will receive 100 mg tablets or 300 mg tablets, broken in half. There will be no dose escalation in this study. 
Dose adjustments or discontinuation of the drug can be made based on adverse events in a participant, which will be 
discussed in a phone call between the participant and Research Coordinator. 
 
11.3.2 Packaging and Labeling 
Trial medication and CGM Freestyle Libre 2 will be dispensed by Curexa Pharmacy 3007 Ocean Heights Ave, Egg Harbor 
Township, NJ 08234, United States. 
 
11.3.3 Storage 
Tablets should be stored at room temperature, away from heat and light. Tablets are dispensed in a tight, light-resistant 
labeled container. 
 
11.4 Concomitant Medications 
If participants fit eligibility criteria but are on other medications, they should continue to take those at the prescribed 
dosages. They will be instructed to tell their other physicians, medical providers, and pharmacists of their enrollment in the 
trial. Any changes to concomitant medications or any planned surgery should be discussed with the PI immediately. 
 
 
12 Adverse Event Reporting 
 
12.1 Adverse Events Definitions 
 
Adverse drug reaction (ADR): a noxious and unintended reaction to a drug at doses normally used in humans for 
prophylaxis, diagnosis, therapy of diseases, or for the modification of physiological function where a causal relationship is at 
least reasonably possible. 

13 
Protocol Number: ALRx008 
 
                    Approval Date: Jan. 24, 2024 
Approval Number: IRCM-2024-384             
 
Continuing Review Date: Jan. 8, 2025 
Adverse event (AE): an adverse occurrence experienced by a study subject during the course of the clinical trial that is not 
necessarily associated with the drug. An AE can, therefore, be any unfavorable and unintended sign (including an abnormal 
laboratory finding), symptom, or disease temporally associated with the use of the investigational product, whether or not 
related to the investigational product. When an AE has been determined to be related to the investigational product, it is 
considered to be an adverse drug reaction. 
 
 
12.2 Serious Adverse Events 
 
Serious adverse events (SAE): any AE that results in death, is life-threatening, requires inpatient hospitalization, is 
persistent, or causes significant disability/incapacity, or causes a congenital anomaly or birth defect. 
Adverse events will be graded according to the system below: 
 
1. 
Grade 1: Asymptomatic or mild symptoms; clinical or diagnostic observations only; no intervention indicated 
(e.g. headache, nausea, abdominal discomfort). 
2. 
Grade 2: Moderate; minimal, local or noninvasive intervention (e.g. vomiting, diarrhea, shortness of breath). 
3. 
Grade 3: Severe; or medically significant but not immediately life threatening; hospitalization or prolongation 
of hospitalization indicated; disabling (e.g. dehydration, hypotension). 
4. 
Grade 4: Life-threatening ; urgent intervention indicated (e.g. respiratory failure, myocardial infarction, liver 
failure). 
5. 
Grade 5: Death related to an AE. 
 
12.3 Reporting of Adverse Events 
 
 
12.3.1 Routine 
 
The principal investigator will be notified about any adverse events. Furthermore, this information will be obtained through 
monitoring forms sent out to participants. 
 
 
The Principal Investigator will document this information in the participant’s medical record. Participants will be asked to 
report any serious adverse event immediately to the Principal Investigator. This can be done by email or phone (after hours 
phone number is available). 
 
AEs will be documented using standard AE reporting (FDA regulations 21CFR314.80 and 21CFR213.32(s)). Both expected 
(already known) and unexpected AEs will be reported. 
 
12.3.2 Expedited 
 
Serious adverse events that occur while the research participant is actively participating in the research study will be 
reported to the IRB within 48 hours for the duration of the study (until study is closed at the IRB). 
 
13 Statistical Analysis 
 
Demographic and baseline characteristics will be summarized using descriptive statistics. Blood tests will be analyzed using 
analysis of variance. Evaluation will be performed by research and medical teams. 

14 
Protocol Number: ALRx008 
 
                    Approval Date: Jan. 24, 2024 
Approval Number: IRCM-2024-384             
 
Continuing Review Date: Jan. 8, 2025 
14 Ethics 
 
14.1 Ethical Conduct of the Study 
 
The study and any amendments will be reviewed by an Institutional Review Board (IRB). The study will be conducted in 
accordance with the ethical principles that have their origins in the Declaration of Helsinki. The study will be conducted in 
accordance with good clinical practices (GCP). 
 
14.2 Participant Information and Consent 
 
Informed consent will be obtained for all subjects enrolled in the study. 
Participants will receive a digital PDF version of the informed consent documentation associated with the study (Appendix 
A). Participants will have the opportunity to ask questions before signing. Participants will respond to individual lines with 
Yes or No to indicate each section was read and understood, and then sign it electronically. 
A study coordinator will ensure the participants have completed the consent form and have agreed to understanding the 
study and implications of being a participant. It will be stressed that: 
1) No benefits of any kind can be expected from participation in this trial 
2) The subjects may withdraw from the trial at any time without a penalty of any kind 
3) There may be risks associated with participating in the trial 
 
Consent will be documented by a free text first and last name field confirming the participant understands the study. Identity 
will be validated by way of state-issued ID upload alongside an image of the participant. All participants will be provided a 
PDF version of the consent form for their reference and storage. 
 
14.3 Study Participant Confidentiality 
All study records for analysis will be de-identified, so that records cannot be directly linked to the participant and are only 
linked to the participant via coded identifiers. Data will be stored on a password-protected HIPAA-compliant cloud service. 
 
 
 
15 Administrative Procedures 
 
15.1 Modifications to the Protocol 
 
Modifications to the protocol will be added to the Clinical Study Protocol and communicated with the IRB. 
 
15.2 Plans for Dissemination of Findings 
 
We intend to disseminate the findings primarily in four ways: 
1) Publications in peer-reviewed medical journals 
2) Lectures at non-scientific public events 
3) Announcements via the AgelessRx website 
4) Outreach to various media outlets 

15 
Protocol Number: ALRx008 
 
                    Approval Date: Jan. 24, 2024 
Approval Number: IRCM-2024-384             
 
Continuing Review Date: Jan. 8, 2025 
16. Reference List 
1. 
Prasanna Kumar KM, Ghosh S, Canovatchel W, Garodia N, Rajashekar S. A review of clinical efficacy and safety 
of canagliflozin 300 mg in the management of patients with type 2 diabetes mellitus. Indian J Endocrinol Metab. 
2017 Jan-Feb;21(1):196-209. doi: 10.4103/2230-8210.196016. PMID: 28217522; PMCID: PMC5240065. 
2. 
Papanikolaou Y, Palmer H, Binns MA, Jenkins DJ, Greenwood CE. Better cognitive performance following a low- 
glycaemic-index compared with a high-glycaemic-index carbohydrate meal in adults with type 2 diabetes. 
Diabetologia. 2006 May;49(5):855-62. doi: 10.1007/s00125-006-0183-x. Epub 2006 Mar 1. PMID: 16508776. 
3. 
Gottfried, Sara MD, “8 Reason Why Glucose is Worth Measuring.” Metabolic Basics. June 17, 2022 
https://www.levelshealth.com/blog/8-reasons-glucose-is-worth-measuring 
4. 
Lin HJ, Lee BC, Ho YL, Lin YH, Chen CY, Hsu HC, Lin MS, Chien KL, Chen MF. Postprandial glucose improves 
the risk prediction of cardiovascular death beyond the metabolic syndrome in the nondiabetic population. Diabetes 
Care. 2009 Sep;32(9):1721-6. doi: 10.2337/dc08-2337. Epub 2009 Jun 5. PMID: 19502543; PMCID: 
PMC2732157. 
5. 
5. Hall H, Perelman D, Breschi A, Limcaoco P, Kellogg R, McLaughlin T, et al. (2018) Glucotypes reveal new 
patterns of glucose dysregulation. PLoS Biol 16(7): e2005143. https://doi.org/10.1371/journal.pbio.2005143 
6. 
David Polidori, Sue Sha, Sunder Mudaliar, Theodore P. Ciaraldi, Atalanta Ghosh, Nicole Vaccaro, Kristin Farrell, 
Paul Rothenberg, Robert R. Henry; Canagliflozin Lowers Postprandial Glucose and Insulin by Delaying Intestinal 
Glucose Absorption in Addition to Increasing Urinary Glucose Excretion: Results of a randomized, placebo- 
controlled study. Diabetes Care 1 August 2013; 36 (8): 2154–2161. https://doi.org/10.2337/dc12-2391 
7. 
Lawrence A. Leiter, Kun-Ho Yoon, Pablo Arias, Gisle Langslet, John Xie, Dainius A. Balis, Dawn Millington, Frank 
Vercruysse, William Canovatchel, Gary Meininger; Canagliflozin Provides Durable Glycemic Improvements and 
Body Weight Reduction Over 104 Weeks Versus Glimepiride in Patients With Type 2 Diabetes on Metformin: A 
Randomized, Double-Blind, Phase 3 Study. Diabetes Care 1 March 2015; 38 (3): 355–364. 
8. 
Rosenthal, N., Meininger, G., Ways, K., Polidori, D., Desai, M., Qiu, R., Alba, M., Vercruysse, F., Balis, D., Shaw, 
W., Edwards, R., Bull, S., Di Prospero, N., Sha, S., Rothenberg, P., Canovatchel, W. and Demarest, K. (2015), 
Canagliflozin: a sodium glucose co-transporter 2 inhibitor for the treatment of type 2 diabetes mellitus. Ann. N.Y. 
Acad. Sci., 1358: 28-43. https://doi.org/10.1111/nyas.12852 
9. 
Heerspink, H., Oshima, M., Shang, H., Li, J., Craig, J., Seeuw, D., Tanna, G., Levin, A., Neal, Bruce., Perkovic, V., 
Wheeler, D., Yavin, Y., Jardine, M. (2022), Canagliflozin and Kidney-Related Adverse Events in Type 2 Diabetes 
and CKD: Findings From the Randomized CREDENCE Trial. Amer J Kindey Diseases., 79(2): 244-256: 
https://doi.org/10.1053/j.ajkd.2021.05.005 
10. Suh, Sunghwan, and Jae Hyeon Kim. “Glycemic Variability: How Do We Measure It and Why Is It Important?.” 
Diabetes & metabolism journal vol. 39,4 (2015): 273-82. doi:10.4093/dmj.2015.39.4.273 

16 
Protocol Number: ALRx008 
 
                    Approval Date: Jan. 24, 2024 
Approval Number: IRCM-2024-384             
 
Continuing Review Date: Jan. 8, 2025 
Appendix 
Appendix A: Informed consent forms 
 
Title of Study: 
The Efficacy and Tolerability of Canagliflozin in Healthy Individuals 
Comparing Dosing Protocols of Canagliflozin for use as a Gerotherapeutic 
 
Principal Investigator: 
Dr. Sajad Zalzala 
Sponsor: 
AgelessRx 
Purpose of the Study: I understand that the purpose of this study is to measure the effects that canagliflozin intervention has on 
reducing average glucose in healthy individuals. 
(Yes/No) 
 
Participation: I understand that participation in this study will last 2 weeks. During the 2-week of participation, I will be asked to 
take 150mg Invokana (canagliflozin) a total of four times or 100mg Invokana (canagliflozin) a total of 7 times, complete four side 
effect and tolerability surveys, complete morning blood pressure recordings, and wear a continuous glucose monitor for the study 
duration. 
(Yes/No) 
 
Canagliflozin: I understand that Canagliflozin is an SGLT2 inhibitor. It is a compound known under the name Invokana, used to 
treat type 2 diabetes by increasing urinary glucose secretion. (Yes/No) 
 
Am I eligible?: I understand that if I am interested in this study, the study coordinator will assess my eligibility following the 
completion of this form. There are no restrictions in ethnicity, gender, socioeconomic status, educational status, sexual 
preference, religious preference, or political views in this study. (Yes/No) 
 
What are the possible benefits of participating in the study?: I understand that AgelessRx cannot promise any benefit for 
participating in this study. There will be no financial benefit to participating in this study. I will be provided with the results of the 
study. 
(Yes/No) 
 
What are the possible risks of taking part in the study?: I understand that there are risks of side effects from taking 
canagliflozin, including hypoglycemia, indigestion, stomach pain, nausea, urinary tract infections, and headache. 
(Yes/No) 
 
How will information be kept confidential?: I understand that health information will be stored in AgelessRx's secured database 
and will be made available only to study collaborators. Study staff will protect your personal information closely. No one will be able 
to connect my responses and any other information that identifies me. Federal or state laws may require AgelessRx to show 
information to university or government officials (or sponsors), who are responsible for monitoring the safety of this study. Directly 
identifying information (e.g. names, addresses) will be safeguarded and maintained under controlled conditions. I will not be 
identified in any publication from this study. Should my information be re-identified, this information will only be made available to 
AgelessRx research staff, the FDA, or the IRB. 
(Yes/No) 
 
What is the cost to participate in the study? I understand that there is no cost required to participate in the study. All costs of trial 
materials will be covered by AgelessRx. 
(Yes/No) 
 
What happens next if I decide to participate in the study?: I understand that if I am selected to participate in the study, the study 
coordinator will reach out to enroll me and order my study materials. (Yes/No) 
 
Where does this study take place? I understand that this study is a virtual trial. Participants can be located in any of the 50 states 
of the USA. All participation will be via telemedicine using the AgelessRx website (agelessrx.com). 
(Yes/No) 

17 
Protocol Number: ALRx008 
 
                    Approval Date: Jan. 24, 2024 
Approval Number: IRCM-2024-384             
 
Continuing Review Date: Jan. 8, 2025 
How can I withdraw from the study?: I understand that if I decide that you would like to withdraw, I can reach out to the study 
coordinator at any time. 
 
Andy Nyquist 
(650) 272-3169 
research@agelessrx.com 
(Yes/No) 
 
Data-sharing: I understand that de-identified data from this study may be shared with the research community at large to advance 
science and health. AgelessRx will remove or code any personal information that could identify me before files are shared with 
other researchers to ensure, by current scientific standards and known methods, that no one will be able to identify me from the 
information we share. Despite these measures, I acknowledge that AgelessRx cannot guarantee the anonymity of my personal 
data. 
(Yes/No) 
 
Future Use of Data: I understand that identifiers might be removed and the de-identified information or biospecimens may be used 
for future research without additional consent. 
(Yes/No) 
 
Information about the results: I understand that information derived from my specimens may be used to generate commercial 
profit. I will not share in any commercial value or other compensation from products developed using this information. 
(Yes/No) 
 
Research Funding: I understand that funding for this study has come entirely from AgelessRx. No government grants were used to 
fund the study. 
(Yes/No) 
 
Voluntary participation and responsibilities of the volunteer: I understand that taking part in this research study is voluntary. If I 
choose to take part in this research, my major responsibilities will include completing multiple questionnaires and completing one 
week of control days and one week of treatment days. On the treatment days, I will take up to 150 mg of canagliflozin, as directed. I 
have the right to stop at any time. If I decide not to participate or if I decide to stop taking part in the research at a later date, there 
will be no penalty or loss of benefits to which I am otherwise entitled. 
 
The AgelessRx investigator may take me out of the research study without my permission. Some possible reasons for this are side 
effects from medications, my own compliance with the study requirements, my use of habit-forming medications or recreational 
drugs, my development of an unrelated illness, a car accident or other accident, or my having a major surgery. Also, the IRCM IRB 
may end the research study early. If my participation in the research ends early, I may be asked to perform final testing at that time. 
If I will be participating in another clinical trial with the same investigators or at the same study sites, or elsewhere, while in this 
research study, I should discuss the procedures and/or treatments with my physician or the investigators. This precaution is 
intended to protect you from possible side effects from interactions of research drugs, treatments, or testing. 
(Yes/No) 
 
Contacting the research team: I understand that I have the right to ask any questions I may have about this research. If I have 
questions, complaints, or concerns or believe I may have developed an injury related to this research, contact the AgelessRx 
Research team at (650) 272-3169. 
Should I wish to contact an impartial third party not associated with this study, I may contact James P. Faber, secretary of the 
Institutional Review Board (IRB) of the Institute of Regenerative and Cellular Medicine (IRCM), which reviewed this study for ethical 
compliance: jpfaber@ircm.org or (786) 271-2156. 
(Yes/No) 
 
Consent to Participate: I understand that by entering my first and last name here you agree that you received this information, 
have asked the questions you currently have about the research, and have received answers to those questions. I will receive a 
copy of the consent form for future reference. 
 
 
 
Participant First and Last Name 
Date 

18 
Protocol Number: ALRx008 
 
                    Approval Date: Jan. 24, 2024 
Approval Number: IRCM-2024-384             
 
Continuing Review Date: Jan. 8, 2025 
Appendix E: Declaration of Helsinki 
This informed consent document has been created using the guidelines established by the National Institutes of Health, 
National Center for Complementary and Integrative Health, 9000 Rockville Pike, Bethesda, Maryland 20892. These 
guidelines were based on the World Medical Association (WMA) Declaration of Helsinki, adopted by the 18th WMA General 
Assembly, Helsinki, Finland, in Jun, 1964; and amended by the: 
 
29th WMA General Assembly, Tokyo, Japan, October 1975 
35th WMA General Assembly, Venice, Italy, October 1983 
41st WMA General Assembly, Hong Kong, September 1989 
48th WMA General Assembly, Somerset West, Republic of South Africa, October 1996 
52nd WMA General Assembly, Edinburgh, Scotland, October 2000 
53rd WMA General Assembly, Washington DC, USA, October 2002 (Note of Clarification added) 55th WMA General Assembly, 
Tokyo, Japan, October 2004 (Note of Clarification added) 
59th WMA General Assembly, Seoul, Republic of Korea, October 2008 
64th WMA General Assembly, Fortaleza, Brazil, October 2013 
 
Preamble 
 
1. 
The World Medical Association (WMA) has developed the Declaration of Helsinki as a statement of ethical 
principles for medical research involving human subjects, including research on identifiable human material and data. 
 
The Declaration is intended to be read as a whole and each of its constituent paragraphs should be applied with 
consideration of all other relevant paragraphs. 
 
2. 
Consistent with the mandate of the WMA, the Declaration is addressed primarily to physicians. The WMA 
encourages others who are involved in medical research involving human subjects to adopt these principles. 
 
General Principles 
 
3. 
The Declaration of Geneva of the WMA binds the physician with the words, “The health of my patient will be my 
first consideration,” and the International Code of Medical Ethics declares that, “A physician shall act in the patient’s best 
interest when providing medical care.” 
 
4. 
It is the duty of the physician to promote and safeguard the health, well-being and rights of patients, including 
those who are involved in medical research. The physician’s knowledge and conscience are dedicated to the fulfilment of 
this duty. 
 
5. 
Medical progress is based on research that ultimately must include studies involving human subjects. 
 
6. 
The primary purpose of medical research involving human subjects is to understand the causes, development and 
effects of diseases and improve preventive, diagnostic and therapeutic interventions (methods, procedures and treatments). 
Even the best proven interventions must be evaluated continually through research for their safety, effectiveness, efficiency, 
accessibility and quality. 
 
7. 
Medical research is subject to ethical standards that promote and ensure respect for all human subjects and 
protect their health and rights. 
 
8. 
While the primary purpose of medical research is to generate new knowledge, this goal can never take 
precedence over the rights and interests of individual research subjects. 
 
9. 
It is the duty of physicians who are involved in medical research to protect the life, health, dignity, integrity, right to 
self-determination, privacy, and confidentiality of personal information of research subjects. The responsibility for the 
protection of research subjects must always rest with the physician or other health care professionals and never with the 
research subjects, even though they have given consent. 

19 
Protocol Number: ALRx008 
 
                    Approval Date: Jan. 24, 2024 
Approval Number: IRCM-2024-384             
 
Continuing Review Date: Jan. 8, 2025 
10. 
Physicians must consider the ethical, legal and regulatory norms and standards for research involving human 
subjects in their own countries as well as applicable international norms and standards. No national or international ethical, 
legal or regulatory requirement should reduce or eliminate any of the protections for research subjects set forth in this 
Declaration. 
 
11. 
Medical research should be conducted in a manner that minimises possible harm to the environment 
. 
12. 
Medical research involving human subjects must be conducted only by individuals with the appropriate ethics and 
scientific education, training and qualifications. Research on patients or healthy volunteers requires the supervision of a 
competent and appropriately qualified physician or other health care professional. 
 
13. 
Groups that are underrepresented in medical research should be provided appropriate access to participation in 
research. 
14. 
Physicians who combine medical research with medical care should involve their patients in research only to the 
extent that this is justified by its potential preventive, diagnostic or therapeutic value and if the physician has good reason to 
believe that participation in the research study will not adversely affect the health of the patients who serve as research 
subjects. 
 
15. 
Appropriate compensation and treatment for subjects who are harmed as a result of participating in research must 
be ensured. 
Risks, Burdens and Benefits 
 
16. 
In medical practice and in medical research, most interventions involve risks and burdens. 
 
Medical research involving human subjects may only be conducted if the importance of the objective outweighs the risks 
and burdens to the research subjects. 
 
17. 
All medical research involving human subjects must be preceded by careful assessment of predictable risks and 
burdens to the individuals and groups involved in the research in comparison with foreseeable benefits to them and to other 
individuals or groups affected by the condition under investigation. 
 
Measures to minimise the risks must be implemented. The risks must be continuously monitored, assessed and 
documented by the researcher. 
 
18. 
Physicians may not be involved in a research study involving human subjects unless they are confident that the 
risks have been adequately assessed and can be satisfactorily managed. 
 
When the risks are found to outweigh the potential benefits or when there is conclusive proof of definitive outcomes, 
physicians must assess whether to continue, modify or immediately stop the study. 
 
Vulnerable Groups and Individuals 
 
19. 
Some groups and individuals are particularly vulnerable and may have an increased likelihood of being wronged or 
of incurring additional harm. 
 
All vulnerable groups and individuals should receive specifically considered protection. 
 
20. 
Medical research with a vulnerable group is only justified if the research is responsive to the health needs or 
priorities of this group and the research cannot be carried out in a non-vulnerable group. In addition, this group should stand 
to benefit from the knowledge, practices or interventions that result from the research. 
 
Scientific Requirements and Research Protocols 

20 
Protocol Number: ALRx008 
 
                    Approval Date: Jan. 24, 2024 
Approval Number: IRCM-2024-384             
 
Continuing Review Date: Jan. 8, 2025 
21. 
Medical research involving human subjects must conform to generally accepted scientific principles, be based on a 
thorough knowledge of the scientific literature, other relevant sources of information, and adequate laboratory and, as 
appropriate, animal experimentation. The welfare of animals used for research must be respected. 
 
22. 
The design and performance of each research study involving human subjects must be clearly described and 
justified in a research protocol. 
 
The protocol should contain a statement of the ethical considerations involved and should indicate how the principles in this 
Declaration have been addressed. The protocol should include information regarding funding, sponsors, institutional 
affiliations, potential conflicts of interest, incentives for subjects and information regarding provisions for treating and/or 
compensating subjects who are harmed as a consequence of participation in the research study. 
 
In clinical trials, the protocol must also describe appropriate arrangements for post-trial provisions. 
 
Research Ethics Committees 
 
23. 
The research protocol must be submitted for consideration, comment, guidance and approval to the concerned 
research ethics committee before the study begins. This committee must be transparent in its functioning, must be 
independent of 
the researcher, the sponsor and any other undue influence and must be duly qualified. It must take into consideration the 
laws and regulations of the country or countries in which the research is to be performed as well as applicable international 
norms and standards but these must not be allowed to reduce or eliminate any of the protections for research subjects set 
forth in this Declaration. 
 
The committee must have the right to monitor ongoing studies. The researcher must provide monitoring information to the 
committee, especially information about any serious adverse events. No amendment to the protocol may be made without 
consideration and approval by the committee. After the end of the study, the researchers must submit a final report to the 
committee containing a summary of the study’s findings and conclusions. 
 
Privacy and Confidentiality 
 
24. 
Every precaution must be taken to protect the privacy of research subjects and the confidentiality of their personal 
information. 
 
Informed Consent 
 
25. 
Participation by individuals capable of giving informed consent as subjects in medical research must be voluntary. 
Although it may be appropriate to consult family members or community leaders, no individual capable of giving informed 
consent may be enrolled in a research study unless he or she freely agrees. 
 
26. 
In medical research involving human subjects capable of giving informed consent, each potential subject must be 
adequately informed of the aims, methods, sources of funding, any possible conflicts of interest, institutional affiliations of 
the researcher, the anticipated benefits and potential risks of the study and the discomfort it may entail, post study 
provisions and any other relevant aspects of the study. The potential subject must be informed of the right to refuse to 
participate in the study or to withdraw consent to participate at any time without reprisal. Special attention should be given to 
the specific information needs of individual potential subjects as well as to the methods used to deliver the information. 
 
After ensuring that the potential subject has understood the information, the physician or another appropriately qualified 
individual must then seek the potential subject’s freely given informed consent, preferably in writing. If the consent cannot be 
expressed in writing, the non-written consent must be formally documented and witnessed. 
All medical research subjects should be given the option of being informed about the general outcome and results of the 
study. 

21 
Protocol Number: ALRx008 
 
                    Approval Date: Jan. 24, 2024 
Approval Number: IRCM-2024-384             
 
Continuing Review Date: Jan. 8, 2025 
27. 
When seeking informed consent for participation in a research study the physician must be particularly cautious if 
the potential subject is in a dependent relationship with the physician or may consent under duress. In such situations the 
informed consent must be sought by an appropriately qualified individual who is completely independent of this relationship. 
 
28. 
For a potential research subject who is incapable of giving informed consent, the physician must seek informed 
consent from the legally authorized representative. These individuals must not be included in a research study that has no 
likelihood of benefit for them unless it is intended to promote the health of the group represented by the potential subject, 
the research cannot instead be performed with persons capable of providing informed consent, and the research entails 
only minimal risk and minimal burden. 
 
29. 
When a potential research subject who is deemed incapable of giving informed consent is able to give assent to 
decisions about participation in research, the physician must seek that assent in addition to the consent of the legally 
authorised representative. The potential subject’s dissent should be respected. 
 
30. 
Research involving subjects who are physically or mentally incapable of giving consent, for example, unconscious 
patients, may be done only if the physical or mental condition that prevents giving informed consent is a necessary 
characteristic of the research group. In such circumstances the physician must seek informed consent from the legally 
authorised representative. If no such representative is available and if the research cannot be delayed, the study may 
proceed without informed consent provided that the specific reasons for involving subjects with a condition that renders 
them unable to give informed consent have been stated in the research protocol and the study has been approved by a 
research ethics committee. Consent to remain in the research must be obtained as soon as possible from the subject or a 
legally authorised representative. 
31. 
The physician must fully inform the patient which aspects of their care are related to the research. The refusal of a 
patient to participate in a study or the patient’s decision to withdraw from the study must never adversely affect the patient- 
physician relationship. 
 
32. 
For medical research using identifiable human material or data, such as research on material or data contained in 
biobanks or similar repositories, physicians must seek informed consent for its collection, storage and/or reuse. There may 
be exceptional situations where consent would be impossible or impracticable to obtain for such research. In such situations 
the research may be done only after consideration and approval of a research ethics committee. 
 
Use of Placebo 
 
33. 
The benefits, risks, burdens and effectiveness of a new intervention must be tested against those of the best 
proven intervention(s), except in the following circumstances: 
Where no proven intervention exists, the use of placebo, or no intervention, is acceptable; or 
 
Where for compelling and scientifically sound methodological reasons the use of any intervention less effective than the 
best proven one, the use of placebo, or no intervention is necessary to determine the efficacy or safety of an intervention 
 
and the patients who receive any intervention less effective than the best proven one, placebo, or no intervention will not be 
subject to additional risks of serious or irreversible harm as a result of not receiving the best proven intervention. 
 
Extreme care must be taken to avoid abuse of this option. 
 
Post-Trial Provisions 
 
34. 
In advance of a clinical trial, sponsors, researchers and host country governments should make provisions for 
post-trial access for all participants who still need an intervention identified as beneficial in the trial. This information must 
also be disclosed to participants during the informed consent process. 
 
Research Registration and Publication and Dissemination of Results 

22 
Protocol Number: ALRx008 
 
                    Approval Date: Jan. 24, 2024 
Approval Number: IRCM-2024-384             
 
Continuing Review Date: Jan. 8, 2025 
35. 
Every research study involving human subjects must be registered in a publicly accessible database before 
recruitment of the first subject. 
 
36. 
Researchers, authors, sponsors, editors and publishers all have ethical obligations with regard to the publication 
and dissemination of the results of research. Researchers have a duty to make publicly available the results of their 
research on human subjects and are accountable for the completeness and accuracy of their reports. All parties should 
adhere to accepted guidelines for ethical reporting. Negative and inconclusive as well as positive results must be published 
or otherwise made publicly available. Sources of funding, institutional affiliations and conflicts of interest must be declared in 
the publication. Reports of research not in accordance with the principles of this Declaration should not be accepted for 
publication. 
 
Unproven Interventions in Clinical Practice 
 
37. 
In the treatment of an individual patient, where proven interventions do not exist or other known interventions have 
been ineffective, the physician, after seeking expert advice, with informed consent from the patient or a legally authorised 
representative, may use an unproven intervention if in the physician’s judgement it offers hope of saving life, re-establishing 
health or alleviating suffering. This intervention should subsequently be made the object of research, designed to evaluate 
its safety and efficacy. In all cases, new information must be recorded and, where appropriate, made publicly available.