Vasculera in Participants With Lipedema an Exploratory Controlled Case Study
Phase: NA
Conditions: Lipedema
Sponsor: Primus Pharmaceuticals

Protocol:  Vasculera® in patients with Lipedema: an exploratory controlled 
case study  
 
NCT05616962 
 
March 19, 2019 

Vasculera® in patients with Lipedema: an exploratory controlled case study 
 
 
 
This document is a confidential communication of the Clinical Development Departments of 
Primus Pharmaceuticals, Inc. Acceptance of this document constitutes agreement that the recipient 
will not disclose or publish any of the information contained herein without prior written 
permission from Primus. The only exception to this rule is that the information may be given to a 
properly constituted IRB with the understanding that they are requested to keep it confidential.
Protocol #: 
PLP-01 
Sponsors: 
Primus Pharmaceuticals, Inc. 
7373 N. Scottsdale Rd., Suite B-200 Scottsdale, AZ 85253  
Tel: 480-483-1410  
Fax: 480-483-2604 
Study Director: 
Robert M. Levy, MD 
Director of Clinical Development  
Tel:       480-483-1410 
Mobile: 480-415-6779 
 
Study Statistician 
MB Clinical Research and Consulting, LLC 
Kevin Maki, PhD 
211 E. Lake Street, Ste. 2 
Addison, IL 60101 
Tel: 630-469-6600 
 
Date: 
March 19, 2019 
Version: 
2 
 

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Protocol Signature and Financial Disclosure Page 
This protocol has been written by Primus Pharmaceuticals, Inc., 
Director of Clinical Development, Robert M. Levy, M.D.
Director of Clinical Development signature 
Date 
I have read and I understand all the provisions and requirements of this protocol, 
Vasculera® in patients with Lipedema: an exploratory controlled case study, PLP-01 I agree to perform 
the investigator’s responsibilities exactly as set forth in the protocol according to the principles of Good 
Clinical Practice. I further understand that all information pertaining to this protocol is confidential and 
may not be disclosed in personal communications or professional presentations without the prior written 
consent of Primus Pharmaceuticals, Inc. 
Investigator signature 
Date 
I certify that, other than the investigator stipend agreed upon in the contract and budget for this study, I have 
no other financial interest in Primus Pharmaceuticals, Inc. or any of its present or future products. 
Investigator signature 
Date 

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Vasculera® in Patients with Lipedema: an exploratory controlled case study 
Synopsis 
Protocol #: PLP-01 
Background 
Lipedema is a condition characterized by abnormal accumulation of subcutaneous fat, predominantly in the 
legs, often associated with interstitial edema. The condition causes disfigurement, pain, functional 
impairment, emotional disturbance and marked reduction in overall quality of life. The cause is unknown 
but is believed to involve both genetic and acquired factors and may involve defective vascular function. 
Treatment modalities consist of surgical removal of large fatty deposits and decompression therapy such as 
compression garments, manual lymphatic drainage, and home sequential pneumatic compression devices; 
dietary control is rarely effective (Buck 2016). 
Vasculera® is a prescription medical food product marketed for management of chronic venous 
insufficiency (CVI) and all its complications, including venous ulcers, and for edema of many etiologies 
(Lyseng-Williamson 2003). Diosmin, the primary ingredient in Vasculera, has been used in Europe for 40 
years as a drug (Daflon®) for treatment of CVI. Its hemodynamic and molecular activities on veins, 
lymphatics, microvasculature and endothelial cells have been studied for many years (Colleridge-Smith 
2000, Ramelot 2005). Anecdotal reports from physicians currently prescribing Vasculera and the use of 
diosmin in the Treatment, Research and Education of Adipose Tissue (TREAT) program at the University 
of Arizona, College of Medicine suggest that diosmin may have benefit in reducing the signs and symptoms 
of lipedema at doses of 500 and 600 mg once or twice daily. (Medications and Supplements 2019). 
The glycocalyx is an ultrathin proteoglycan membrane covering all endothelial surfaces (Alphonsus 2014, 
Pillinger 2017). Although described more than 60 years ago, it is only within the past ~15 years that rigorous 
investigation of glycocalyx structure and function has been accomplished. Although endothelial cells have 
been generally thought to be a site of action for diosmin (Shoab 1999), several of the known features of the 
mechanism of action of diosmin and of glycocalyx activity suggest that the primary target of diosmin may 
be the glycocalyx rather than the endothelial cell itself. There are several commonly measured entities, of 
which we have chosen to measure two, syndecan-1 and heparan sulfate as exploratory outcomes (Mensah 
2017).

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Study design 
This will be a three (3) month open-label case study. Patients with lipedema (see Appendix III for diagnostic 
criteria) present for at least one (1) year who have not taken any diosmin containing medications within the 
1 year prior to the screening visit and meet all other inclusion and exclusion criteria will be eligible for 
participation. At the screening visit patients will have the study explained to them and those wishing to 
participate will sign an Informed Consent Document (ICD). Demographic information will be recorded, 
measurements of vital signs, weight, and Body Mass Index (BMI) and leg circumference will be recorded. 
Subjects will complete a Short WOMAC and complete a series of assessments on numerical rating scales 
of 0 to 10, as listed below under efficacy measurements. Women of child bearing potential will have a urine 
pregnancy test performed, results of which must be negative to continue in the study. A blood sample for 
markers of glycocalyx function will be drawn. Subjects will then take one (1) Vasculera tablet BID for the 
duration of the study. Subjects will return to the clinic monthly at which times they will again complete the 
rating scales. At the final visit a blood sample for glycocalyx function markers will again be drawn and 
investigators will complete a 5-point Response to Therapy Likert scale. Adverse events will be recorded at 
all follow-up visits. 
If subjects are receiving any form of manual leg decompression therapy, the type and frequency should 
remain unchanged for one (1) week prior to the baseline visit and for the duration of the study. In addition, 
subjects should not have any decompression for one (1) week prior to any study related clinic visit. 
Study objectives 
This case study is designed to gain preliminary information via a uniform protocol regarding the clinical 
effects of Vasculera in patients with lipedema and the possible role of the glycocalyx as a physiological 
target for Vasculera activity. It is anticipated that the results of this case study will inform the development 
of a formal randomized, double-blind, placebo controlled trial. 
Efficacy measurements 
1- Subject weight 
2- Leg circumference 2 and 12 inches above lateral malleoli of both legs 
3- BMI 
4- Short WOMAC 
5- Subject-assessments, on a 0-10 rating scale, for: 
• 
leg discomfort 
• 
feeling of leg swelling/tightness 
• 
leg tenderness 
• 
leg bruising 
• 
leg skin redness 
• 
fatigue 
• 
ability to perform activities of daily living (ADL) 
• 
overall sense of well-being 
6- 
Investigator assessment of response to therapy by 5-point Likert scale 

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Exploratory Measures 
Plasma glycocalyx markers 
Safety measurements 
Adverse event recording 
Study product dosing and rationale 
Vasculera 630 mg BID 
Vasculera is marketed for management of venous insufficiency at a dose of 630 mg (one tablet, 95% purity) 
daily. Most of the literature, almost all of which is from historical use in Europe uses doses of 500 mg (90% 
purity) BID. The literature suggests that 600 mg of 95% product is the equivalent of 500 mg of 90% product 
for treatment of the early stages of CVI but anecdotal evidence suggest that BID dosing of Vasculera 
performs better than QD dosing in more severe stages of CVI and other disorders. 
Inclusion criteria 
1- established diagnosis of lipedema (see Appendix III) for at least one (1) year 
2- women, ages 20 to 70 years 
3- score of at least 4 out of 10 on a rating scale of 0-10 (10=worst) for overall sense of well being 
4- able to read and understand Informed Consent Document (ICD) and all questionnaires in English or 
with family/friend translator 
5- not pregnant or lactating; women of child bearing potential must use an approved method of birth 
control (Appendix II). 
6- be willing to stop compression therapy for one week prior to each visit 
Exclusion criteria 
1- other forms of leg enlargement, including lymphedema without coexisting lipedema 
2- any primary systemic vasculopathy 
3- history of exposure to Vasculera or other diosmin containing medication within one (1) year of the 
screening visit 
4- concomitant use of warfarin, platelet inhibitors, factor Xa inhibitors or any medication intended to 
reduce blood coagulability 
5- concomitant use of diclofenac, metronidazole or chlorzoxazone 
6- uncontrolled hypertension (BP>170/110), unstable cardiac disease, active skin ulceration 
7- any other disease or condition that, in the opinion of the investigator, might put the 
subject at risk by participation in this study OR confound evaluation of response to Vasculera 
7- history of substance abuse within one (1) year of the screening visit or of current alcohol consumption 
more than one (1) unit daily. For purposes of this study, a unit of alcohol will be considered to be 12 oz 
of beer, 6 oz of wine or 1 ^ oz of hard spirits. 
Number of subjects 
It is estimated that 30 subjects will be sufficient to obtain a meaningful efficacy signal. 
Length of study 
It is estimated that it will take 2 months to recruit the required number of subjects. The total length of the 

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study is anticipated to be five (5) months. 
Statistical considerations 
Descriptive statistics will be presented for all relevant variables including demographic variables 
such as age, sex, weight and BMI for each group. Descriptive statistics for baseline and endpoint 
values for all study variables, including weight, BMI leg circumference, short WOMAC, 
investigator Likert and all subject reported outcomes per section 4.2 will also be presented. Data 
from baseline and final visit will be compared by Student’s t-test (paired). P values </= 0.05 will 
be considered of significance. 
 
 

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Vasculera® in Patients with Lipedema: an exploratory case controlled study 
Protocol #: PLP-01 
1.0 Background 
Lipedema is a condition characterized by abnormal accumulation of subcutaneous fat, predominantly in the 
legs, often associated with interstitial edema. The condition causes disfigurement, pain, functional 
impairment, emotional disturbance and marked reduction in overall quality of life. The cause is unknown 
but is believed to involve both genetic and acquired factors and may involve defective vascular function. 
Treatment modalities consist of surgical removal of large fatty deposits and decompression therapy such as 
compression garments, manual lymphatic drainage, and home sequential pneumatic compression devices; 
dietary control is rarely effective (Buck 2016). 
Vasculera® is a prescription medical food product marketed for management of chronic venous 
insufficiency (CVI) and all its complications, including venous ulcers, and for edema of many etiologies 
(Lyseng-Williamson 2003). Diosmin, the primary ingredient in Vasculera, has been used in Europe for 40 
years as a drug (Daflon®) for treatment of CVI. Its hemodynamic and molecular activities on veins, 
lymphatics, microvasculature and endothelial cells have been studied for many years (Colleridge-Smith 
2000, Ramelot 2005). 
Anecdotal reports from physicians currently prescribing Vasculera and the use of diosmin in the Treatment, 
Research and Education of Adipose Tissue (TREAT) program at the University of Arizona, College of 
Medicine suggest that diosmin may have benefit in reducing the signs and symptoms of lipedema at doses 
of 500-600 mg once or twice daily. (Medications and Supplements 2019). 
The glycocalyx is an ultrathin proteoglycan membrane covering all endothelial surfaces (Alphonsus 2014, 
Pillinger 2017). Although described more than 60 years ago, it is only within the past ~15 years that rigorous 
investigation of glycocalyx structure and function has been accomplished. Although endothelial cells have 
been generally thought to be a site of action for diosmin (Shoab 1999), several of the known features of the 
mechanism of action of diosmin and of glycocalyx activity suggest that the primary target of diosmin may 
be the glycocalyx rather than the endothelial cell itself. Several components of GCX structure which are 
liberated into blood are commonly measured to assess GCX status. In this study, blood levels of syndecan-
1 and heparin sulfate will be measured as exploratory outcomes (Mensah 2017). 
2.0 Study objectives 
This exploratory case study is designed to gain preliminary information via a uniform protocol regarding 
the clinical effects of Vasculera in patients with lipedema and the possible role of the glycocalyx as a 
physiological target for Vasculera activity. It is anticipated that the results of this case study will inform the 
development of a formal randomized, double-blind, placebo controlled trial. 

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3.0 Study product 
All subjects will receive Vasculera 630 mg BID. No dose modifications are anticipated. 
3.1 Dose rationale 
Vasculera is marketed for management of venous insufficiency at a dose of 630 mg (one tablet, 95% purity) 
daily. Most of the literature, almost all of which is from historical use in Europe, uses doses of 500 mg (90% 
purity) BID. The literature also suggests that 600 mg of 95% product is the equivalent of 500 mg of 90% 
product for treatment of the early stages of CVI but anecdotal evidence suggest that BID dosing of Vasculera 
performs better than QD dosing in more severe stages of CVI and other disorders. Anecdotal reports from 
physicians currently prescribing Vasculera and the use of diosmin in the Treatment, Research and Education 
of Adipose Tissue (TREAT) program at the University of Arizona, College of Medicine suggest that diosmin 
may have benefit in reducing the signs and symptoms of lipedema at doses of 500-600 mg once or twice 
daily. (Medications and Supplements 2019). 
4.0 Study design 
This will be a three (3) month open-label case study. Patients with lipedema (see appendix III for 
diagnostic criteria) present for at least one (1) year who have not taken any diosmin containing 
medications within the 1 year prior to the screening visit and meet all other inclusion and exclusion criteria 
will be eligible for participation. At the baseline visit and all follow-up visits subjects will complete a 
Short WOMAC and self-assessments on a 0-10 rating scale for: 
• 
leg discomfort 
• 
feeling of leg swelling/tightness 
• 
leg tenderness 
• 
leg bruising 
• 
leg skin redness 
• 
fatigue 
• 
ability to perform activities of daily living (ADL) 
• 
overall sense of well-being 
If subjects are receiving any form of decompression therapy such as compression garments, manual 
lymphatic drainage, or home sequential pneumatic compression devices; the type and frequency should 
remain unchanged for at least one (1) week prior to the baseline visit and for the duration of the study. In 
addition, subjects should not have any decompression for one (1) week prior to any study related clinic 
visit. 
A blood sample (10 cc) will be drawn for glycocalyx markers (heparin sulfate and syndecan-1) at the 
baseline and final (3 month) visits. Investigators will complete a 5-point Likert scale for response to 
therapy at the 3 month visit. 
4.1 Concomitant medications and procedures 
All subjects may continue their usual medication regimen, including diuretics, but the dose of these should 

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remain constant throughout the duration of the study. Similarly, subjects receiving decompressive therapy 
should continue their usual regimen for the duration of the study. Any changes in medication or procedural 
regimen should be noted on the appropriate case report form together with the reason for the change. 
4.2 Efficacy measurements 
1- Subject weight 
2- Leg circumference 2 and 12 inches above malleoli 
3- BMI 
4- Short WOMAC 
5- Self-assessment on a 0-10 rating scale for: 
• leg discomfort 
• feeling of leg swelling/tightness 
• leg tenderness 
• leg bruising 
• leg skin redness 
• fatigue 
• ability to perform activities of daily living (ADL) 
• overall sense of well-being 
6- Investigator assessment of response to therapy by 5-point Likert scale 
Exploratory Measure 
Plasma glycocalyx markers 
4.3 Safety measurements 
Adverse event recording 
4.4 Number of subjects 
It is estimated that 30 subjects will be sufficient to obtain a meaningful efficacy signal. 
5.0 Study selection criteria 
5.1 Inclusion criteria 
1- established diagnosis of lipedema (see appendix III) for at least one (1) year 
2- women, ages 20 to 70 years 
3- score of at least 4 out of 10 on self-assessment on a 0-10 scale (10=worst) for overall sense of well 
being 
4- able to read and understand all questionnaires in English or with family/friend translator 
5- not pregnant or lactating; women of child bearing potential should use an approved method of birth 
control for the duration of the study 

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6- be willing to stop compression therapy for one week prior to each visit 
5.2 exclusion criteria 
1- other forms of leg enlargement, including lymphedema 
2- any primary systemic vasculopathy 
3- history of exposure to Vasculera or other diosmin containing medication within one (1) year of the 
screening visit 
4- concomitant use of warfarin, platelet inhibitors, factor Xa inhibitors or any medication intended to 
reduce blood coagulability 
5- concomitant use of diclofenac, metronidazole or chlorzoxazone 
6- uncontrolled hypertension (BP>170/110), unstable cardiac disease, active skin ulceration 
7- any other disease or condition that, in the opinion of the investigator, might put the 
subject at risk by participation in this study OR confound evaluation of response to Vasculera 
8- history of substance abuse within one (1) year of the screening visit or of current alcohol consumption 
more than one (1) unit daily. For purposes of this study, a unit of alcohol will be considered to be 12 oz 
of beer, 6 oz of wine or 1 'A oz of hard spirits. 
6.0 Study procedures 
6.1 Screening visit 
At the screening visit patients will have the study explained to them and those wishing to participate will 
sign an Informed Consent Document (ICD). Prospective subjects must be allowed to take the ICD home 
prior to signing to consider and/or discuss with family, if they wish to do so. Subject eligibility will be 
determined according to the established inclusion and exclusion criteria. Women of child bearing potential 
(WOCBP) will have a urine pregnancy test performed, results of which must be negative to continue in the 
study. 
6.2 Baseline visit (visit 1) 
The baseline visit may occur at the same time as the screening visit if the subject wishes to participate, 
signs the ICD and meets all study entry requirements. The following procedures will then be performed: 
1- Brief physical examination 
2- urine pregnancy test for WOCBP 
3- Medical history and current medications 
4- Vital signs (blood pressure, pulse) 
5- Subject weight and height 
6- Leg circumference 2 and 12 inches above the lateral malleoli on both legs 
7- BMI (see appendix V) 
9- Blood draw (10 cc) for glycocalyx markers 
8- Short WOMAC 
10- Self-assessment on a 0-10 rating scale for: 
• leg discomfort 
• feeling of leg swelling/tightness 

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• leg tenderness 
• leg bruising 
• leg skin redness 
• fatigue 
• ability to perform activities of daily living (ADL) 
• overall sense of well-being 
11- 
dispense study medication 
6.3 Visit 2 (1 month) 
At the one (1) month visit, the following procedures will be performed. 
1- Vital signs 
2- Subject weight 
3- Leg circumference 2 and 12 inches above the lateral malleoli on both legs 
4- All self-assessments as above 
5- Record adverse events 
6- Record changes/new medications 
7- Collect and count used study medication 
8- Dispense new bottle of study medication 
6.4 Visit 3 (2 month) 
At the two (2) month visit, the following procedures will be performed. 
1- Vital signs 
2- Subject weight 
3- Leg circumference 2 and 12 inches above the lateral malleoli on both legs 
4- All self-assessments as above 
5- Record adverse events 
6- Record changes/new medications 
7- Collect and count used study medication 
8- Dispense new bottle of study medication 
6.5 Visit 4 (3 month, final) 
1- Brief physical examination 
2- vital signs (blood pressure, pulse) 
3- Subject weight 
4- Leg circumference 2 and 12 inches above the lateral malleoli on both legs 
5- BMI (see appendix XXX for table) 
6- Blood draw (10 cc) for glycocalyx markers 
7- Investigator Likert for response to therapy 

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8- All self-assessments, as above 
9- Record adverse events 
10- Record changes/new medications 
11- Collect and count used study medication 
 
7.0 
Study Withdrawal 
Subjects may be withdrawn from the study for one or more of the following reasons: 
• 
Noncompliance with the protocol 
• 
Unacceptable adverse event. In this case the decision to remove the subject from the study may be 
made by the subject, the investigator or Primus. 
• 
Determination by the investigator or Primus that termination of the subject’s participation in the 
study is in the subject’s best medical interest or for an administrative reason other than an adverse 
event. 
• 
The use of any excluded medication. If the subject is discontinued prior to receiving the first dose 
of study drug AEs and SAEs will not be collected. If the subject has received study medication, 
AEs and SAEs will be collected until the termination visit or until 30 days after the last dose of 
study drug, whichever is longer. All AEs and SAEs must be followed until resolution or stability. 
• 
Request for withdrawal by the subject for any reason whether or not related to an AE. 
• 
Lost to follow-up. 
According to FDA administrative law and the Declaration of Helsinki a subject in a clinical trial has the 
right to withdraw at any time and for any reason without prejudicing his/her future medical care at the 
investigative site. Investigators and sponsors may withdraw subjects because of intercurrent illness, AEs, 
treatment failure, protocol violation or other administrative reasons. In the case of early withdrawal of a 
subject, the investigator should make all reasonable efforts to have the subject attend a termination visit and 
document all details of the early termination on the appropriate CRF. 
8.0 
Early Termination Visit Procedures 
If a subject wishes to end his/her participation in the study prematurely, whether because of an AE or any 
other reason, he/she should be asked to complete a termination visit at the next scheduled appointment or 
within 14 days, whichever is more convenient. The investigator should make every reasonable attempt to 
perform the final assessment. Whenever possible, all final visit procedures should be performed at the time 
of an early termination visit. All outstanding AEs should be followed to resolution or stability. The reason 
for early termination should be clearly stated on the Early Termination CRF. 
9.0 
Withdrawals Due to Adverse Events 
All adverse events that result in a subject’s withdrawal from the study must be reported to the Primus 
Director of Clinical Development, Robert Levy, MD, (480-415-6779) within 24-hours for SAEs and ten 
working days for non-serious AEs. 

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10.0 
Definition of Adverse Event 
An AE is any untoward or unexpected medical occurrence in a subject participating in a clinical study 
whether or not there is a possible relationship between the investigative agent and the event. For 
purposes of this study, AE collection will begin after the first dose of study product.  
 
10.1 
Serious Adverse Events 
SAEs require special attention, management and documentation. All SAEs must be reported to Primus 
within 24 hours whether or not they are considered by the investigator to be related to the study agent 
(s). 
An SAE is any medical event that: 
• 
results in death 
• 
is life threatening—the investigator believes the subject’s life is in immediate danger (This does 
not include events that, had they been more severe, might have been life threatening) 
• 
requires in-patient hospitalization or prolongation of an existing hospitalization 
• 
results in permanent disability 
• 
is a congenital anomaly or birth defect 
• 
requires medical or surgical intervention to prevent one of the outcomes above 
Although cancer is no longer considered an SAE by the FDA, Primus requires notification of such 
diagnoses within 48 hours of the time the investigator first learns of the event. 
10.2 
Severity of Adverse Events 
The investigator must rate every AE for severity according to the following guidelines: 
 
1 = Mild 
The event does not interfere with daily activities. 
2 = Moderate 
The event discomfort and/or dysfunction is enough to interfere 
with, but not prevent, daily activities. 
3 = Severe 
The event causes significant impairment of ability to perform 
daily activities. 
4 = Life-
threatening 
The event, if, in the opinion of the investigator or sponsor places 
the subject at immediate risk of death. 
 
 

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10.3 
Assessment of Causality 
Investigators will be responsible for determining the relationship of the study agent(s) 
AE and will record their conclusions on the CRF adverse event page. It is recognized 
causality often cannot be established with certainty and relies on clinical judgement. 
After careful medical evaluation there is little or no doubt that 
the study agent is the direct etiologic cause of the AE. 
This situation is most commonly seen when an AE recurs after 
re-challenge with study agent. 
After careful scrutiny of the available medical facts, there is a 
reasonable, but inconclusive, certainty that the event is related to 
the study agent. 
Those events for which other etiologies cannot be clearly demonstrated 
and for which a relationship to the study agent cannot be positively 
excluded. 
Those AEs for which other causes are more likely. 
Those AEs for which other etiologies can clearly and 
conclusively be defined. Investigators must use their best clinical 
judgment keeping in mind the following questions: 
• 
Was study drug administered 
• 
What was the temporal relationship between the administration of study drug and the AE? Was 
this consistent with the nature of the AE? 
• 
Was there another obvious or possible cause for the AE? 
• 
Was the AE consistent with the known effects of the study drug? 
• 
Were there any features of the subject’s clinical state, concomitant medications or diseases or 
environmental factors that could have caused or modified the AE? 
• 
Did the AE resolve, improve, remain stable or worsen after the study drug was stopped or the 
dose reduced? 
• 
If the subject was re-exposed to the study agent (re-challenge), did the AE recur, worsen or 
remain unchanged? Re-challenge should be attempted only after careful consideration and only 
after discussion with Primus.
to the 
that 
1 = Definitely Related 
2 = Probably Related 
3 = Possibly Related 
4 = Unlikely 
5 = Not Related 

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10.4 
Reporting Serious Adverse Events 
SAEs must be reported to Primus by telephone within 24 hours from the time the investigator first 
learns of them. This should be followed by a faxed report outlining the details of the event and the 
investigator’s assessment of the severity and relationship of the event to the study agent. All SAEs 
will be reported on both the AE and SAE pages of the case report forms. In addition: 
• 
A new SAE form must be completed and faxed to Primus within 24 hours 
• 
Follow-up SAE forms must be completed and faxed to Primus whenever new information 
becomes available about the event 
• 
A final SAE report must be completed and faxed to Primus when the event has resolved or 
its consequences have stabilized and all relevant information (including hospital records, 
laboratory and pathology reports, autopsy reports, etc.) have been received. It is the 
responsibility of the investigator to obtain copies of all relevant information in a timely 
manner. 
• 
It is the responsibility of the investigator to determine the severity and causality of the SAE. 
• 
The initial SAE and all subsequent reports must be retained in the subject’s study file 
together with a telephone log of all contacts with Primus and the subject. These should be 
recorded at the time of the conversation, dated and signed by the investigator or his/her 
representative and should include the name of the person with whom the conversation was 
held. 
Telephone contact should be made with: 
Robert Levy, MD, Director Clinical Development Tel: 
480-483-1410 Mobile: 480-415-6779 Fax: 480-483-
2604 
Primus will review all SAEs with the investigator and a decision will be made regarding the need 
for further action. Primus’ primary concern will be subject safety, both for the subject having the 
event as well as for the other subjects in the study. If, after detailed review, it is determined that a 
subject safety issue exists, Primus will notify all investigators participating in any trial with the 
same study agent and may require one or more of the following: 
• 
Discontinuation or suspension of the study 
• 
Modification of the protocol 
• 
Modification of the informed consent document to reflect additional risk(s) to be signed by 
current and future subjects 
• 
Addition of newly discovered adverse events to the investigator’s brochure 
10.5 Follow-Up of Adverse Events 
All adverse events, whether serious or non-serious, must be followed until resolution or stability. 
This follow-up may extend beyond the end of the study. Primus considers AE follow-up to be part 
of a study. Therefore, a study cannot be closed at an investigative site if an AE is outstanding. 
Any serious AE occurring after the conclusion of a study must be reported to Primus if the 
investigator thinks the event may be causally related to the study agent. 

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10.6 Deaths 
All deaths, regardless of cause, that occur between the time a subject signs an informed consent 
document and the final study visit or 30 days after the last dose of study product, whichever is 
longer, must be reported to Primus by telephone with a follow-up fax within 24 hours of the 
investigator becoming aware of the death. This applies whether or not the subject has received study 
product and whether or not the study product is thought to be causally related to the death. 
It is the investigator’s responsibility to obtain all relevant medical records and autopsy reports and 
forward them to Primus as soon as possible. 
10.7 Reporting Safety Information to IRB 
It is the responsibility of the investigator to notify his/her IRB of any unexpected or previously 
unknown risk to study subjects. This includes death from any cause and all SAEs. The investigator 
should make this report in accordance with the requirements of the IRB. The report should include 
any action taken after discussion of the SAE with Primus. 
10.8 Managing Adverse Events 
All AEs and SAEs should be medically managed according to the best medical standards available 
in the investigator’s community. Except in the case of emergent treatment and routine care the 
management of the event should be discussed with Primus. Decisions regarding re-challenge with 
study product must be made in consultation with Primus. 
10.9 Pregnancy 
Although pregnancy is not considered to be an adverse event, Primus requires that investigators 
provide notice of any pregnancy in an active study subject or within 30 days of the last dose of study 
drug. Primus also requires investigators to provide follow-up information on the pregnancy and the 
health of the infant. 
The informed consent document, signed by the patient, must contain information about the potential 
risks to pregnant women and/or to a fetus. Subjects must be advised to use contraception during and 
for 30 days after their participation in the study. 
11. 
Ethical Considerations 
This study will be conducted in accordance with the principles of the Declaration of Helsinki, ICH guidelines 
and Good Clinical Practices (GCPs) and US FDA regulations. 
11.1 
Informed Consent 
All patients must read and sign the Research Subject Information and Consent Document (ICD) 
before they can be subjects in this research study. It is the investigator’s responsibility to fully 
inform the patient about the procedures, risks and benefits of the study and to answer, in a manor 
clearly understandable to the patient, all the patient’s questions. The ICD must be signed and dated 
by the patient, the investigator and a witness. A copy of the signed and dated ICD must be given to 
the subject. The IRB approved ICD must not be modified in any way from its original, IRB 

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approved form. The original copy of the ICD must be retained with the subject’s study file and is 
subject to inspection by representatives of Primus and the regulatory agencies. 
ICDs and all other written material distributed to subject during the study must be written in a 
language the subject understands. 
A model informed consent form can be found on the IRB website. 
11.1.1 Institutional Review Board (IRB) 
Primus will assume responsibility for submitting the protocol and ICD to a central IRB. 
Before this can be done each investigator must submit the following to Primus: 
• 
Signed and dated protocol signature page 
• 
Completed, signed and dated FDA Form 1572 
• 
Completed, signed and dated W-9 form 
• 
Current curriculum vitae for investigator and all sub-investigators, signed and 
dated 
If an investigator wishes to use an IRB other than that selected by Primus, he/she may do 
so after obtaining approval from Primus. In this case, the investigator will be responsible 
for all required submissions. Any changes to the model ICD must be first approved by 
Primus, in writing. The investigator must agree to all protocol amendments and, if 
necessary, make appropriate changes in the ICD. The IRB should be notified of any such 
changes and IRB approval must be sought for any changes involving subject safety. Serious 
or unexpected adverse events must be reported to the IRB within one week of their 
occurrence. 
11.1.2 Subject Confidentiality 
Subject identities should be protected at all times. This is the legal responsibility of the investigator. 
Subjects should be identified in study documents only by initials and study number on any 
document sent to Primus or a regulatory agency. Documents that are only for office use must be 
kept in strict confidence 
Investigators must allow representatives of Primus or government regulatory agencies to inspect 
study records but the identity of the subjects should remain confidential. 
12. 
Administrative and legal obligations 
12.1 
Pre-study Documentation 
Before an investigator can begin screening subjects and before shipment of study agent can commence 
the investigator must complete and return the following to Primus: 
• 
Signed and dated protocol signature page 

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• 
Completed, signed and dated FDA Form 1572 
• 
Copy of IRB approved ICD 
• 
Copy of IRB approval letter for the study and ICD 
• 
Membership list of IRB (usually supplied with approval letter) 
• 
Current CVs of the investigator and all sub-investigators, signed and dated 
• 
Signed and dated contract to conduct the study under the conditions and financial arrangements 
specified 
• 
Name and contact information of person(s) responsible for the day to day management of the 
study 
12.2 
Protocol Amendments 
Protocol amendments may be made only by Primus. The investigator’s IRB must be informed of any 
amendments that may affect subject safety or the conduct of the study. The IRB must issue a letter of 
approval of such amendments. The investigator must keep the original letter in the study’s regulatory 
binder and forward a copy of the letter to Primus. 
12.3 
Study Termination 
Both the investigator and Primus have the right to terminate their participation in the study. If this is 
done by the investigator he/she must provide a detailed explanation of the action to Primus and the IRB 
and a copy of this account must be retained with the regulatory file. 
12.4 
Case Report Forms (CRFs) 
Primus will provide investigators with sets of NCR paper CRFs bearing information identifying the 
study site and the principle investigator. All data obtained during the course of the study will be recorded 
on the CRFs. The CRFs should be reviewed on site for completeness by the investigator or his/her 
representative. The original will be forwarded to Primus and a copy will remain with the subject’s study 
data file. 
CRFs contain the critical study data and are the basis from which results are tabulated, analyses 
performed and final reports made. Therefore, it is essential that data recorded on the CRFs be legible, 
complete and accurate. Forms should be typed or completed in black ball point ink. Corrections should 
be made by placing a single line through the error, adding the correct data then initialing and dating the 
correction. Under no circumstances should the original entry be erased, overwritten or obscured by 
white-out or some other method. CRFs should contain only subject initials and study number. Names 
or other identifying information should not appear. All data points must be answered. If the information 
is unknown or unavailable the terms “NA” (not available), “ND” (not done), “SU” (subject unable) or 
“DP” (data pending) may be used. 
12.5 Final Study Documentation and Storage 
Investigators must retain all study records in a secure location, safe from environmental damage, 
for a minimum of two (2) years or as required by Primus. If, for any reason, the investigator becomes 
unable to store study documents Primus will assume responsibility for storage. Study documents 
should never be destroyed without the written consent of Primus. 

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13. 
Summary of Investigator responsibilities 
Investigator responsibilities include, but are not necessarily limited to the 
following. He/she will: 
• 
conduct the study according to the protocol and will make no changes without the consent of the 
sponsor. This requirement is not intended to limit the investigator’s ability to deviate from the 
protocol to protect the health and welfare of a subject. 
• 
comply with all applicable regulatory requirements. 
• 
personally supervise the conduct of the study. 
• 
be responsive to input from study subjects as their observations are often 
helpful 
• 
inform subjects that the study product is investigational. 
• 
report any adverse events that occur in the course of the study. Non-serious AE’s may be reported 
on the CRF’s. Serious AE’s must be reported to Primus within 24 hours and to the applicable IRB 
in accordance with the requirements of the IRB. 
• 
promptly treat or arrange for treatment of any AE or SAE 
• 
follow any AE until its resolution even if that endpoint occurs after the close of the 
study. 
• 
make a statement on the AE reporting form as to whether, in the investigator’s judgment, the AE 
was or was not related to the study agent 
• 
use a properly constituted IRB for study approval and oversight. 
• 
supply Primus with a current curriculum vitae. 
• 
review all CRF’s for accuracy and completeness. 
• 
maintain complete and accurate records of all study related documents for two (2) years 
14. 
Primus contacts 
Questions related to SAE’s, medical observations or interventions should be directed to: 
Robert Levy, MD 
Director of Clinical Development 
Primus Pharmaceuticals, Inc. 
7373 N. Scottsdale Rd. 
Ste. B-200 
Scottsdale, AZ 85253 Tel: 480-483-1410 Cell: 480-415-6779 Fax: 480-483-2604 
Questions related to study operational issues may be addressed to Dr. Levy or to: 
Mary Sanstead, RN, BSN, Project manager Tel: 480-843-1410 Cell: 480-250-6689 Fax: 480-
483-2604 
15. 
Publication/presentation of data 
Primus regards all information obtained from the conduct of this study as confidential. If 
an investigator wishes to publish or present in oral or written form all or part of the data 
obtained during the study he/she must first submit a complete copy of such presentation to 
the director of Clinical Investigation for review and approval. This submission must occur 
no later than sixty (60) days before the anticipated date of presentation. The investigator 
will be required to incorporate any suggestions made by Primus consistent with its right to 

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protect the confidentiality of the information. 
16. 
Statistical considerations 
This is a pilot, exploratory case study designed to inform development of a formal RBCDB 
clinical trial. As such, only those variables clearly shown to be affected by the study treatment 
will be incorporated into the formal trial. 
Descriptive statistics will be presented for all relevant variables including demographic variables 
such as age, sex, weight and BMI for each group. Descriptive statistics for baseline and endpoint 
values for all study variables, including weight, BMI leg circumference, short WOMAC, 
investigator Likert and all subject reported outcomes per section 4.2 will also be presented. Data 
from baseline and final visit will be compared by Student’s t-test (paired). P values </= 0.05 will 
be considered of significance. 
17. 
References 
Alphonsus CS, Rodseth RN. The endothelial glycocalyx: a review of the vascular 
barrier.Anaesthesia.2014.69:777-84 
Buck DW, Herbst KL. Lipedema: a relatively common disease with extremely common misconceptions. 
PlasReconstr Surg Glob Open. 2016. Doi: 10.1097/GOX.1043. 
Colleridge-Smith PD. Micronized purified flavonoid fraction and the treatment of chronic venous 
insufficiency: microcirculatory mechanisms. Microcirc. 2000.7:S35-40. 
Herbst KL. Medications and Supplements. (2019, March 18). Retrieved from 
https://treat.medicine.arizona.edu/treatments-therapies/ 
Herbst KL. Rare adipose disorders (RADs) masquerading as obesity. Acta Pharmacologica Sinica. 
2012.33:155-72. 
its use in chronic venous insufficiency, venous ulcers and haemorrhoids, Drugs. 2003.63:71100. 
Lyseng-Williamson KA, Perry CM. Micronized purified flavonoid fraction: a review of 
Mensah SA, Cheng MJ, Homayoni H, Plouffe BD, Coury AJ, Ebong EE. Regeneration of glycocalyx by 
heparan sulfate and sphingosine 1-phosphate restores inter-endothelial communication. PLoS One. 
2017;12(10):e0186116. Published 2017 Oct 12. doi:10.1371/journal.pone.0186116 
Pillinger NL, Kam PCA. Endothelial glycocalyx: basic science and clinical implications. Anaesth Intens 
Care. 2017.45:1-13. 
Ramelot AA. Daflon 500 mg: symptoms and edema clinical update. Angiology.2005.56 (suppl 1):S25-
32.y 
Shoab SS, Porter J, Scurr JH, Coleridge-Smith PD. Endothelial activation response to oral micronized 
flavonoid therapy in patients with chronic venous disease—a prospective study. Eur J Vasc Endovsac 
Surg. 1999.17:313-8. 
Wold LE, Hines EA, Jr., Allen EV. Lipedema of the legs: a syndrome characterized by fat legs and edema. 
Ann Intern Med. 1951.34:1243-50.

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Appendix I 
The World Medical Association Declaration of Helsinki 
World Medical Association Declaration of Helsinki: Recommendations Guiding Medical 
Doctors in Biomedical Research Involving Human Subjects 
Adopted by the 18th World Medical Assembly, Helsinki, Finland, 1964 and as last revised by 
the World Medical Assembly in Seoul, Korea 2008 
Introduction 
It is the mission of the physician to safeguard the health of the people. His or her knowledge and conscience 
are dedicated to the fulfillment of this mission. 
The Declaration of Geneva of the World Medical Association 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 only in the patient's interest when providing medical care which might have the 
effect of weakening the physical and mental condition of the patient." 
The Purpose of biomedical research involving human subjects must be to improve diagnostic, therapeutic 
and prophylactic procedures and the understanding of the etiology and pathogenesis of disease. 
In current medical practice most diagnostic, therapeutic or prophylactic procedures involve hazards. This 
applies especially to biomedical research. 
Medical progress is based on research which ultimately must rest in part on experimentation involving 
human subjects. 
In the field of biomedical research a fundamental distinction must be recognized between medical research 
in which the aim is essentially diagnostic or therapeutic for a patient, and medical research, the essential 
object of which is purely scientific and without implying direct diagnostic or therapeutic value to the person 
subjected to the research. 
Special caution must be exercised in the conduct of research which may affect the environment, and the 
welfare of animals used for research must be respected. 
Because it is essential that the results of laboratory experiments be applied to human beings to further 
scientific knowledge and to help suffering humanity, the World Medical Association has prepared the 
following recommendations as a guide to every physician in biomedical research involving human subjects. 
They should be kept under review in the future. It must be stressed that the standards as drafted are only a 
guide to physicians all over the world. Physicians are not relieved from criminal, civil and ethical 
responsibilities under the laws of their own countries. 

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I. Basic Principles 
1. Biomedical research involving human subjects must conform to generally accepted scientific 
principles and should be based on adequately performed laboratory and animal experimentation and 
on a thorough knowledge of the scientific literature. 
2. The design and performance of each experimental procedure involving human subjects should be 
clearly formulated in an experimental protocol which should be transmitted for consideration, 
comment and guidance to a specially appointed committee independent of the investigator and the 
sponsor provided that this independent committee is in conformity with the laws and regulations of 
the country in which the research experiment is performed. 
3. Biomedical research involving human subjects should be conducted only by scientifically qualified 
persons and under the supervision of a clinically competent medical person. The responsibility for 
the human subject must always rest with a medically qualified person and never rest on the subject 
of the research, even though the subject has given his or her consent. 
4. Biomedical research involving human subjects cannot legitimately be carried out unless the 
importance of the objective is in proportion to the inherent risk to the subject. 
5. Every biomedical research project involving human subjects should be preceded by careful 
assessment of predictable risks in comparison with foreseeable benefits to the subject or to others. 
Concern for the interests of the subject must always prevail over the interests of science and society. 
6. The right of the research subject to safeguard his or her integrity must always be respected. Every 
precaution should be taken to respect the privacy of the subject and to minimize the impact of the 
study on the subject's physical and mental integrity and on the personality of the subject. 
7. Physicians should abstain from engaging in research projects involving human subjects unless they 
are satisfied that the hazards involved are believed to be predictable. Physicians should cease any 
investigation if the hazards are found to outweigh the potential benefits. 
8. In publication of the results of his or her research, the physician is obliged to preserve the accuracy 
of the results. Reports of experimentation not in accordance with the principles laid down in this 
Declaration should not be accepted for publication. 
9. In any research on human beings, each potential subject must be adequately informed of the aims, 
methods, anticipated benefits and potential hazards of the study and the discomfort it may entail. 
He or she should be informed that he or she is at liberty to abstain from participation in the study 
and that he or she is free to withdraw his or her consent to participation at any time. The physician 
should then obtain the subject's freely-given informed consent, preferably in writing. 
10. When obtaining informed consent for the research project the physician should be particularly 
cautious if the subject is in a dependent relationship to him or her or may consent under duress. In 
that case the informed consent should be obtained by a physician who is not engaged in the 
investigation and who is completely independent of this official relationship. 
11. In case of legal incompetence, informed consent should be obtained from the legal guardian in 
accordance with national legislation. Where physical or mental incapacity makes it impossible to 
obtain informed consent, or when the subject is a minor, permission from the responsible relative 
replaces that of the subject in accordance with national legislation. 
Whenever the minor child is in fact able to give a consent, the minor's consent must be obtained in 
addition to the consent of the minor's legal guardian. 
12. The research protocol should always contain a statement of the ethical considerations involved and 
should indicate that the principles enunciated in the present Declaration are complied with. 

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II. Medical Research Combined with Professional Care (Clinical Research) 
1. In the treatment of the sick person, the physician must be free to use a new diagnostic and therapeutic 
measure, if in his or her judgment it offers hope of saving life, reestablishing health or alleviating 
suffering. 
2. The potential benefits, hazards and discomfort of a new method should be weighed against the 
advantages of the best current diagnostic and therapeutic methods. 
3. In any medical study, every patient--including those of a control group, if any--should be assured 
of the best proven diagnostic and therapeutic method. 
4. The refusal of the patient to participate in a study must never interfere with the physician- patient 
relationship. 
5. If the physician considers it essential not to obtain informed consent, the specific reasons for this 
proposal should be stated in the experimental protocol for transmission to the independent 
committee (I,2). 
6. The physician can combine medical research with professional care, the objective being the 
acquisition of new medical knowledge, only to the extent that medical research is justified by its 
potential diagnostic or therapeutic value for the patient. 
III. Non-Therapeutic Biomedical Research Involving Human Subjects (Non-Clinical 
Biomedical Research) 
1. In the purely scientific application of medical research carried out on a human being, it is the duty 
of the physician to remain the protector of the life and health of that person on whom biomedical 
research is being carried out. 
2. The subjects should be volunteers--either healthy persons or patients for whom the experimental 
design is not related to the patient's illness. 
3. The investigator or the investigating team should discontinue the research if in his/her or their 
judgment it may, if continued, be harmful to the individual. 
4. In research on man, the interest of science and society should never take precedence over 
considerations related to the well-being of the subject.

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Appendix II 
Acceptable Contraceptive Measures 
1- Oral contraceptives 
2- Depo Provera 
3- norplant implants 
4- Intra-uterine device 
5- Tubal ligation 
6- Vasectomy 
7- Condom plus diaphragm 
8- condom plus contraceptive sponge or spermicidal jelly

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Appendix III 
Diagnostic Features of Lipedema 
From Wold 1951; modified by Herbst 2012 
• 
Women 
• 
Usual onset at puberty, pregnancy or menopause 
• 
Symmetrical adipose hypertrophy of lower extremities, sparing trunk and feet, with sharp 
demarcation at ankles (cuffing). Upper extremities may or may not be involved. 
• 
Negative Stemmer sign 
• 
Easy Bruising 
• 
Minimal pitting edema 
• 
Pain, often spontaneous, tenderness on palpation 
• 
No response to leg elevation or weight loss

APPENDIX IV 
SCHEDULE OF EVENTS 
 
 
VISIT 
V1 
V2 
V3 
V4 
DAY/WEEK 
Screen/ 
Baseline 
1 Month 
2 Month 
3 Month 
Window 
+/- 2d 
+/- 2d 
+/- 2d 
+/- 2d 
Informed Consent 
X 
 
 
 
Demographics 
X 
 
 
 
Current Medication 
X 
 
 
 
Medical History 
X 
 
 
 
Inclusion/Exclusion 
X 
 
 
 
Vital Signs (BP, P) 
X 
X 
X 
X 
Weight/Height 
X 
X 
X 
X 
Brief Physical Exam 
X 
 
 
 
Urine Pregnancy Test 
X 
 
 
 
Leg Circumference1 
X 
X 
X 
X 
BMI2 
X 
 
 
X 
Leg Discomfort 
X 
X 
X 
X 
Feeling of Leg Swelling/Tightness 
X 
X 
X 
X 
Leg Tenderness 
X 
X 
X 
X 
Leg Bruising 
X 
X 
X 
X 
Leg Skin Redness 
X 
X 
X 
X 
Fatigue 
X 
X 
X 
X 
Ability to Perform ADLs 
X 
X 
X 
X 
Overall Sense of Well-Being 
X 
X 
X 
X 
Short WOMAC 
X 
X 
X 
X 
Draw Bld for Glycocalyx Markers 
X 
 
 
X 
Dispense Product 
X 
X 
X 
 
Adverse Events 
 
X 
X 
X 
Concomitant Medications 
X 
X 
X 
X 
Collect and Count Product 
 
X 
X 
X 
Likert Scale Investigator Response to 
Therapy 
 
 
 
X 
1 Measure 2 and 12 inches above the lateral malleoli on both legs 2 Use only the chart provided 
 

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APPENDIX V: Body Mass Index Table 
 
 
To use the table, find the appropriate height in the left-hand column labeled Height. Move across to a given weight. The number at 
the top of the column is the BMI at that height and weight. Pounds have been rounded off. 
BMI 
19 
20 
21 
22 
23 
24 
25 
26 
27 
28 
29 
30 
31 
32 
33 
34 
3
Height 
(inches) 
Body Weight (pounds) 
58 
91 
96 100 105 
110 115 
119 124 129 
134 138 143 148 
153 158 162 
16
59 
94 
99 104 109 
114 119 
124 128 133 
138 143 148 153 
158 163 168 
17
60 
97 102 
107 112 
118 123 
128 133 138 
143 148 153 158 
163 168 174 
17
61 
100 106 
111 116 
122 127 
132 137 143 
148 153 158 164 
169 174 180 
18
62 
104 109 
115 120 
126 131 
136 142 147 
153 158 164 169 
175 180 186 
19
63 
107 113 
118 124 
130 135 
141 146 152 
158 163 169 175 
180 186 191 
19
64 
110 116 
122 128 
134 140 
145 151 157 
163 169 174 180 
186 192 197 
20
65 
114 120 
126 132 
138 144 
150 156 162 
168 174 180 186 
192 198 204 
21
66 
118 124 
130 136 
142 148 
155 161 167 
173 179 186 192 
198 204 210 
21
67 
121 127 
134 140 
146 153 
159 166 172 
178 185 191 198 
204 211 217 
22
68 
125 131 
138 144 
151 158 
164 171 177 
184 190 197 203 
210 216 223 
23
69 
128 135 
142 149 
155 162 
169 176 182 
189 196 203 209 
216 223 230 
23
70 
132 139 
146 153 
160 167 
174 181 188 
195 202 209 216 
222 229 236 
24
71 
136 143 
150 157 
165 172 
179 186 193 
200 208 215 222 
229 236 243 
25
72 
140 147 
154 162 
169 177 
184 191 199 
206 213 221 228 
235 242 250 
25
73 
144 151 
159 166 
174 182 
189 197 204 
212 219 227 235 
242 250 257 
26
74 
148 155 
163 171 
179 186 
194 202 210 
218 225 233 241 
249 256 264 
27
75 
152 160 
168 176 
184 192 
200 208 216 
224 232 240 248 
256 264 272 
27
76 
156 164 
172 180 
189 197 
205 213 221 
230 238 246 254 
263 271 279 
28

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Appendix VI 
Blood Sample Processing 
I. FREEZE PLASMA WITHIN ONE (1) HOUR OF DRAWING 
II. Shipping boxes and exterior labeling will be provided. 
III. Samples will be shipped in 2 separate batches. 
IV. Draw and process as directed below. 
1. Complete one lab requisition for each draw; v1 and v4 
2. Draw 10 ml blood into lavender top K2 EDTA tube 
3. Centrifuge for 15 minutes at 5000 rpm 
4. Decant or pipette plasma into two (2) 3 ml cryovials 
5. Label each cryovial with cryo-pen: 
a. Subject initials   
Ex: ABC or A-C  
b. 3-digit study number  
Ex: site 1 subject 4 = 104 (Site # = 1-digit, Subj # = 2-digits) 
c. Date and time of draw  Ex: mm/dd/yy 9:05 am or 1:20 pm 
d. Visit number = 1 or 4  Ex: v1 or v4 
6. Store at -70o F within 1 hour of drawing 
At study completion: 
1. Retain one sample for each subject at -70o F 
2. Ship one sample in dry ice to: 
Attn: Eno Ebong Laboratory 
Chemical Engineering Department 
Northeastern University  
360 Huntington Ave., 335 ISEC 
Boston MA 02115-5000 
 
3. After arrival of first shipment is confirmed, ship second batch.