HELP Study: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Efficacy and Safety Study to Evaluate DX-2930 For Long-Term Prophylaxis Against Acute Attacks of Hereditary Angioedema (HAE)
Phase: PHASE3
Conditions: Hereditary Angioedema (HAE)
Sponsor: Shire

Ⱬᴅ᷄᷉Ⱡ᷊᷇
ⱪꞌ꞉ꜜ꞉ᴐԜꞌͼᴁᴟ꞉Ԝꞌͼ͟ᴟꜝᴡꜝᴐꜝꞌⱡͼⱫᴅ᷄᷉Ⱡ᷊᷊᷇᷄᷇
ⱨꜛᴒꜜᴑꜛᴒꜜᴡͼ᷊᷅᷇ⱴ꞉ꜜԜꞌⱡͼ᷇ⱠͼꜗԜꜜᴢԜᴟᴦ᷉᷇᷈ⅎ
ⱪꜝꜜⱱ꞉ᴑᴒꜜᴡ꞉Ԝꞌ
͟ԜⱲᴒͼ᷈
ⱫᴦԜᴥͼⱪꜝᴟꜞ᷅
Clinical Trial Protocol: DX-2930-03
Study Title:
ⱶⱬꜙ͟ͼᴀᴡᴢᴑᴦᴁꜚⱡͼⱨͼꜚᴢꞌᴡ꞉ᴐᴒꜜᴡᴒᴟԓͼϸԜꜜᴑꜝꜛ꞉ᴧᴒᴑԓͼⱫꜝᴢԝꞌᴒ᷄Ⱪꞌ꞉ꜜᴑԓͼ͟ꞌԜᴐᴒԝꜝ᷄
ⱪꜝꜜᴡᴟꜝꞌꞌᴒᴑͼⱬⱱⱱ꞉ᴐԜᴐᴦͼԜꜜᴑͼᴀԜⱱᴒᴡᴦͼᴀᴡᴢᴑᴦͼᴡꜝͼⱬᴣԜꞌᴢԜᴡᴒͼⱫᴅ᷄᷉Ⱡ᷊᷇ͼⱴꜝᴟͼ
ꜙꜝꜜⱲ᷄ᴁᴒᴟꜛͼ͟ᴟꜝꜞⱳᴦꞌԜᴥ꞉ᴠͼⱨⱲԜ꞉ꜜᴠᴡͼⱨᴐᴢᴡᴒͼⱨᴡᴡԜᴐꞋᴠͼꜝⱱͼⱶᴒᴟᴒᴑ꞉ᴡԜᴟᴦͼ
ⱨꜜⱲ꞉ꜝᴒᴑᴒꜛԜͼӿⱶⱨⱬԐͼ
Study Number:
Ⱬᴅ᷄᷉Ⱡ᷊᷊᷇᷄᷇
Study Phase:
͟ⱳԜᴠᴒͼ᷊
Product Name:
Ⱬᴅ᷄᷉Ⱡ᷊᷇
IND Number:
᷈᷈⅍⅍᷾ⅎ
EudraCT Number:
᷿᷊᷉᷇᷈᷄᷇᷇Ⱡ᷊᷾᷄᷉᷇
Indication:
͟ᴟᴒᴣᴒꜜᴡ꞉ꜝꜜͼꜝⱱͼԜꜜⱲ꞉ꜝᴒᴑᴒꜛԜͼԜᴡᴡԜᴐꞋᴠͼ꞉ꜜꜞԜᴡ꞉ᴒꜜᴡᴠͼᴤ꞉ᴡⱳͼⱶⱨⱬ
Investigators:
ꜚᴢꞌᴡ꞉ᴐᴒꜜᴡᴒᴟ
Sponsor:
ⱫᴦԜᴥͼⱪꜝᴟꜞ᷅ԓͼԜꜜͼ꞉ꜜᴑ꞉ᴟᴒᴐᴡԓͼᴤⱳꜝꞌꞌᴦ᷄ꜝᴤꜜᴒᴑͼᴠᴢԝᴠ꞉ᴑ꞉Ԝᴟᴦͼꜝⱱͼᴀⱳ꞉ᴟᴒͼꜞꞌᴐ᷅
᷿᷿ͼ꜠ᴒᴡᴤꜝᴟꞋͼⱫᴟ꞉ᴣᴒԓͼⱩᴢᴟꞌ꞉ꜜⱲᴡꜝꜜԓͼꜚⱨͼ᷇᷈˲᷊᷇ͼᴂᴀⱨ
Sponsor Contact:
ꜗᴒꜜꜜ꞉ⱱᴒᴟͼᴀᴐⱳᴟԜꜜᴧԓͼꜚⱫ
ԓͼⱪꞌ꞉ꜜ꞉ᴐԜꞌͼⱫᴒᴣᴒꞌꜝꜞꜛᴒꜜᴡ
᷊᷇᷇ͼᴀⱳ꞉ᴟᴒͼᴄԜᴦԓͼꜙᴒᴥ꞉ꜜⱲᴡꜝꜜԓͼꜚⱨͼ᷇᷉᷾᷉᷈ͼᴂᴀⱨ
͟ⱳꜝꜜᴒⱡͼ
Medical Monitor
US and Canada:
ԓͼꜚⱫ
ԓͼⱪꞌ꞉ꜜ꞉ᴐԜꞌͼⱫᴒᴣᴒꞌꜝꜞꜛᴒꜜᴡ
᷊᷇᷇ͼᴀⱳ꞉ᴟᴒͼᴄԜᴦԓͼꜙᴒᴥ꞉ꜜⱲᴡꜝꜜԓͼꜚⱨͼ᷇᷉᷾᷉᷈ͼᴂᴀⱨ
͟ⱳꜝꜜᴒⱡͼ
ͼ
Medical Monitor 
Europe and Jordan:
ԓͼꜚⱫ
ԓͼⱪꞌ꞉ꜜ꞉ᴐԜꞌͼⱫᴒᴣᴒꞌꜝꜞꜛᴒꜜᴡ
᷊᷇᷇ͼᴀⱳ꞉ᴟᴒͼᴄԜᴦԓͼꜙᴒᴥ꞉ꜜⱲᴡꜝꜜԓͼꜚⱨͼ᷇᷉᷾᷉᷈ͼᴂᴀⱨ
͟ⱳꜝꜜᴒⱡͼ
ͼ
Date:
Original Protocol
᷈᷾ͼᴀᴒꜞᴡᴒꜛԝᴒᴟͼ᷿᷉᷇᷈
Amendment 1.0
᷈᷾ͼⱫᴒᴐᴒꜛԝᴒᴟͼ᷿᷉᷇᷈
Amendment 2.0
᷉᷈ͼⱨꜞᴟ꞉ꞌͼ᷉᷇᷈⅍
Amendment 3.0
᷇ⱠͼꜗԜꜜᴢԜᴟᴦͼ᷉᷇᷈ⅎ
Confidentiality Statement
ᴁⱳ꞉ᴠͼᴑꜝᴐᴢꜛᴒꜜᴡͼ꞉ᴠͼᴡⱳᴒͼꜞᴟꜝꜞᴒᴟᴡᴦͼꜝⱱͼⱫᴦԜᴥͼⱪꜝᴟꜞ᷅ͼᴁⱳᴒͼ꞉ꜜⱱꜝᴟꜛԜᴡ꞉ꜝꜜͼ꞉ꜜͼᴡⱳ꞉ᴠͼᴑꜝᴐᴢꜛᴒꜜᴡͼᴐꜝꜜᴡԜ꞉ꜜᴠͼᴡᴟԜᴑᴒͼᴠᴒᴐᴟᴒᴡᴠͼԜꜜᴑͼ
ᴐꜝꜛꜛᴒᴟᴐ꞉Ԝꞌͼ꞉ꜜⱱꜝᴟꜛԜᴡ꞉ꜝꜜͼᴡⱳԜᴡͼԜᴟᴒͼꜞᴟ꞉ᴣ꞉ꞌᴒⱲᴒᴑͼꜝᴟͼᴐꜝꜜⱱ꞉ᴑᴒꜜᴡ꞉ԜꞌͼԜꜜᴑͼꜛԜᴦͼꜜꜝᴡͼԝᴒͼᴑ꞉ᴠᴐꞌꜝᴠᴒᴑͼᴤ꞉ᴡⱳꜝᴢᴡͼᴡⱳᴒͼᴒᴥꜞᴟᴒᴠᴠͼᴤᴟ꞉ᴡᴡᴒꜜͼ
ꜞᴒᴟꜛ꞉ᴠᴠ꞉ꜝꜜͼꜝⱱͼⱫᴦԜᴥͼᴢꜜꞌᴒᴠᴠͼᴟᴒꜟᴢ꞉ᴟᴒᴑͼԝᴦͼⱱᴒᴑᴒᴟԜꞌͼꜝᴟͼᴠᴡԜᴡᴒͼꞌԜᴤͼꜝᴟͼᴟᴒⱲᴢꞌԜᴡ꞉ꜝꜜᴠ᷅ͼⱨꜜᴦͼꜞᴒᴟᴠꜝꜜͼᴡꜝͼᴤⱳꜝꜛͼᴡⱳᴒͼ꞉ꜜⱱꜝᴟꜛԜᴡ꞉ꜝꜜͼ
꞉ᴠͼᴑ꞉ᴠᴐꞌꜝᴠᴒᴑͼꜛᴢᴠᴡͼԝᴒͼ꞉ꜜⱱꜝᴟꜛᴒᴑͼᴡⱳԜᴡͼᴡⱳᴒͼ꞉ꜜⱱꜝᴟꜛԜᴡ꞉ꜝꜜͼ꞉ᴠͼꜞᴟ꞉ᴣ꞉ꞌᴒⱲᴒᴑͼꜝᴟͼᴐꜝꜜⱱ꞉ᴑᴒꜜᴡ꞉ԜꞌͼԜꜜᴑͼꜛԜᴦͼꜜꜝᴡͼԝᴒͼⱱᴢᴟᴡⱳᴒᴟͼᴑ꞉ᴠᴐꞌꜝᴠᴒᴑͼ
ԝᴦͼᴡⱳᴒꜛ᷅ͼᴁⱳᴒᴠᴒͼᴟᴒᴠᴡᴟ꞉ᴐᴡ꞉ꜝꜜᴠͼꜝꜜͼᴑ꞉ᴠᴐꞌꜝᴠᴢᴟᴒͼᴤ꞉ꞌꞌͼԜꜞꜞꞌᴦͼᴒꜟᴢԜꞌꞌᴦͼᴡꜝͼԜꞌꞌͼⱱᴢᴡᴢᴟᴒͼ꞉ꜜⱱꜝᴟꜛԜᴡ꞉ꜝꜜͼᴠᴢꜞꜞꞌ꞉ᴒᴑͼᴡꜝͼᴦꜝᴢͼᴡⱳԜᴡͼ꞉ᴠͼ
꞉ꜜᴑ꞉ᴐԜᴡᴒᴑͼԜᴠͼꜞᴟ꞉ᴣ꞉ꞌᴒⱲᴒᴑͼꜝᴟͼᴐꜝꜜⱱ꞉ᴑᴒꜜᴡ꞉Ԝꞌ᷅
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD

PROTOCOL SIGNATURE PAGE 
Study Title: 
HELP Study™: A Multicenter, Randomized, Double-
Blind, Placebo-Controlled Efficacy and Safety Study to 
Evaluate DX-2930 For Long-Term Prophylaxis Against 
Acute Attacks of Hereditary Angioedema (HAE) 
Study Number: 
DX-2930-03 
Amendment 3.0 Final Date: 
09 January 2017 
This clinical study protocol was subject to critical review and has been approved by the 
Sponsor. The signature ofthe Sponsor representative indicates that the Sponsor will comply 
with all Sponsor obligations detailed in applicable regulations and guidelines and will ensure 
the Investigator is informed of all relevant information that becomes available. 
 Clinical Develop
, Lexington, MA 02421 
Date: 
I have read the foregoing protocol and agree that it contains all necessary details for carrying 
out this study. I will conduct the study in compliance with the Declaration ofHelsinki, GCP, 
and all applicable regulatory requirements and guidelines as outlined herein and will 
complete the study within the time designated. 
I will provide copies of the protocol and all pertinent information to all individuals 
responsible to me who assist in the conduct of this study. I will discuss this material with 
them to ensure they are fully informed regarding the drug and the conduct of the study. 
I will use only the informed consent form approved by Dyax Corp. and my Institutional 
Review Board (IRB), Research Ethics Board (REB) or Ethics Committee (EC) and will 
fulfill all responsibilities for submitting pertinent information to the IRB/REB/EC 
responsible for this study. 
I further agree that Dyax Corp. or their designees shall have access to any source documents 
from which eCRF information may have been generated. 
By signing this protocol, I agree to adhere to the instructions and procedures described in it 
and thereby to adhere to the principles of GCP to which it conforms. 
Signed: _______________ _ 
Date: ________ _ 
Investigator 
Address: 
Ⱬᴅ᷄᷉Ⱡ᷊᷇
ⱪꞌ꞉ꜜ꞉ᴐԜꞌͼᴁᴟ꞉Ԝꞌͼ͟ᴟꜝᴡꜝᴐꜝꞌⱡͼⱫᴅ᷄᷉Ⱡ᷊᷊᷇᷄᷇
ⱨꜛᴒꜜᴑꜛᴒꜜᴡͼ᷊᷅᷇ⱴ꞉ꜜԜꞌⱡͼ᷇ⱠͼꜗԜꜜᴢԜᴟᴦ᷉᷇᷈ⅎ
ⱪꜝꜜⱱ꞉ᴑᴒꜜᴡ꞉Ԝꞌ
͟ԜⱲᴒͼ᷉
ⱫᴦԜᴥͼⱪꜝᴟꜞ᷅
PPD
PPD
PPD
PPD

Ⱬᴅ᷄᷉Ⱡ᷊᷇
ⱪꞌ꞉ꜜ꞉ᴐԜꞌͼᴁᴟ꞉Ԝꞌͼ͟ᴟꜝᴡꜝᴐꜝꞌⱡͼⱫᴅ᷄᷉Ⱡ᷊᷊᷇᷄᷇
ⱨꜛᴒꜜᴑꜛᴒꜜᴡͼ᷊᷅᷇ⱴ꞉ꜜԜꞌⱡͼ᷇ⱠͼꜗԜꜜᴢԜᴟᴦ᷉᷇᷈ⅎ
ⱪꜝꜜⱱ꞉ᴑᴒꜜᴡ꞉Ԝꞌ
͟ԜⱲᴒͼ᷊
ⱫᴦԜᴥͼⱪꜝᴟꜞ᷅
AMENDMENT SUMMARY AND RATIONALE
ⱨꜛᴒꜜᴑꜛᴒꜜᴡͼ᷊ͼᴡꜝͼ͟ᴟꜝᴡꜝᴐꜝꞌͼⱫᴅ᷄᷉Ⱡ᷊᷊᷇᷄᷇ͼ꞉ꜜᴐꞌᴢᴑᴒᴠͼᴡⱳᴒͼⱱꜝꞌꞌꜝᴤ꞉ꜜⱲͼᴟᴒᴣ꞉ᴠ꞉ꜝꜜᴠⱡ

ⱨᴑᴑᴒᴑͼᴒⱱⱱ꞉ᴐԜᴐᴦͼꜛᴒԜᴠᴢᴟᴒͼᴡꜝͼԜᴠᴠᴒᴠᴠͼᴡⱳᴒͼꜜᴢꜛԝᴒᴟͼꜝⱱͼⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟ᷄ᴐꜝꜜⱱ꞉ᴟꜛᴒᴑͼⱶⱨⱬͼԜᴡᴡԜᴐꞋᴠͼ
ꜝᴐᴐᴢᴟᴟ꞉ꜜⱲͼꜝꜜͼⱫԜᴦͼ᷈᷾ͼᴡⱳᴟꜝᴢⱲⱳⱫԜᴦ᷈˲᷉ᴡꜝͼᴟԜꜜꞋͼꜝᴟᴑᴒᴟᴒᴑͼᴠᴒᴐꜝꜜᴑԜᴟᴦͼᴒⱱⱱ꞉ᴐԜᴐᴦͼᴒꜜᴑꜞꜝ꞉ꜜᴡᴠͼⱱꜝᴟͼ
꞉ꜜᴐꞌᴢᴠ꞉ꜝꜜͼ꞉ꜜͼᴡⱳᴒͼꜛᴢꞌᴡ꞉ꜞꞌᴒͼᴡᴒᴠᴡ꞉ꜜⱲͼꜞᴟꜝᴐᴒᴑᴢᴟᴒӿᴡⱳ꞉ᴟᴑͼ꞉ꜜͼᴡⱳᴒͼᴟԜꜜꞋͼꜝᴟᴑᴒᴟԐͼᴡꜝͼԝᴒᴡᴡᴒᴟͼᴢꜜᴑᴒᴟᴠᴡԜꜜᴑͼ
ᴡⱳᴒͼᴒᴥꜞꜝᴠᴢᴟᴒ᷄ᴟᴒᴠꜞꜝꜜᴠᴒͼᴟᴒꞌԜᴡ꞉ꜝꜜᴠⱳ꞉ꜞͼᴠ꞉ꜜᴐᴒͼᴑԜᴡԜͼⱱᴟꜝꜛͼ͟ⱳԜᴠᴒͼ᷈ԝͼᴠᴡᴢᴑᴦͼӿⱫᴅ᷄᷉Ⱡ᷊᷇᷄᷇᷉Ԑͼ
ᴠᴢⱲⱲᴒᴠᴡᴒᴑͼᴡⱳԜᴡͼꞌԜꜜԜᴑᴒꞌᴢꜛԜԝͼӿⱫᴅ᷄᷉Ⱡ᷊᷇ԐͼⱳԜᴠͼԜͼꜛᴒԜꜜͼᴒꞌ꞉ꜛ꞉ꜜԜᴡ꞉ꜝꜜͼⱳԜꞌⱱ᷄ꞌ꞉ⱱᴒͼꜝⱱͼԜꜞꜞᴟꜝᴥ꞉ꜛԜᴡᴒꞌᴦͼ
᷈᷾ͼᴑԜᴦᴠͼᴤⱳᴒᴟᴒͼ꞉ᴡͼ꞉ᴠͼԜꜜᴡ꞉ᴐ꞉ꜞԜᴡᴒᴑͼᴡⱳԜᴡͼ᷿᷇ӼͼᴠᴡᴒԜᴑᴦͼᴠᴡԜᴡᴒͼ꞉ᴠͼԜᴐⱳ꞉ᴒᴣᴒᴑͼ꞉ꜜͼⱶⱨⱬͼᴠᴢԝ꞊ᴒᴐᴡᴠͼԜꜜᴑͼ
ꞌԜꜜԜᴑᴒꞌᴢꜛԜԝͼᴒᴥꜞꜝᴠᴢᴟᴒͼᴟᴒԜᴐⱳᴒᴠͼᴟᴒԜᴠꜝꜜԜԝꞌᴒͼꞌᴒᴣᴒꞌᴠͼԜᴠᴠꜝᴐ꞉Ԝᴡᴒᴑͼᴤ꞉ᴡⱳͼᴡⱳᴒᴟԜꜞᴒᴢᴡ꞉ᴐͼᴒⱱⱱᴒᴐᴡ᷅ͼ

ᴂꜞᴑԜᴡᴒᴑͼᴡⱳᴒͼꜛᴢꞌᴡ꞉ꜞꞌ꞉ᴐ꞉ᴡᴦͼꜞᴟꜝᴐᴒᴑᴢᴟᴒͼԝᴦͼԜᴑᴑ꞉ꜜⱲͼᴡⱳᴒͼᶰⱴԜꜛ꞉ꞌᴦͼ᷾ͼӿⱴ᷾Ԑᶱͼⱳᴦꜞꜝᴡⱳᴒᴠ꞉ᴠͼᴡᴒᴠᴡͼᴡꜝͼᴡⱳᴒͼ
᷊᷄ԝᴟԜꜜᴐⱳͼⱲᴒꜜᴒᴟԜꞌͼⱲԜᴡᴒꞋᴒᴒꜞ꞉ꜜⱲͼꜞᴟꜝᴐᴒᴑᴢᴟᴒͼӿꜞᴟᴒᴣ꞉ꜝᴢᴠꞌᴦͼᴤ꞉ᴡⱳͼ᷊ͼⱱԜꜛ꞉ꞌ꞉ᴒᴠͼꜝⱱͼⱳᴦꜞꜝᴡⱳᴒᴠᴒᴠԐͼⱱꜝᴟͼ
ᴡⱳᴒͼᴡⱳ꞉ᴟᴑͼᴟԜꜜꞋᴒᴑͼᴠᴒᴐꜝꜜᴑԜᴟᴦͼᴒⱱⱱ꞉ᴐԜᴐᴦͼᴒꜜᴑꜞꜝ꞉ꜜᴡ᷅ͼͼ
꜠ꜝᴡᴒᴤꜝᴟᴡⱳᴦͼᴐⱳԜꜜⱲᴒᴠͼᴡꜝͼᴡⱳᴒͼꜞᴟꜝᴡꜝᴐꜝꞌͼԜᴟᴒͼᴐԜꜞᴡᴢᴟᴒᴑͼ꞉ꜜͼᴡⱳᴒͼᴡԜԝꞌᴒͼԝᴒꞌꜝᴤ᷅ⱨᴑᴑ꞉ᴡ꞉ꜝꜜԜꞌͼꜛ꞉ꜜꜝᴟͼᴟᴒᴣ꞉ᴠ꞉ꜝꜜᴠͼ
꞉ꜜͼⱲᴟԜꜛꜛԜᴟԓͼᴠꜞᴒꞌꞌ꞉ꜜⱲԓͼꜞᴢꜜᴐᴡᴢԜᴡ꞉ꜝꜜԓͼԜꜜᴑͼⱱꜝᴟꜛԜᴡͼⱳԜᴣᴒͼԝᴒᴒꜜͼꜛԜᴑᴒͼⱱꜝᴟͼᴐꞌԜᴟ꞉ᴡᴦͼԜꜜᴑͼԜᴟᴒͼꜜꜝᴡͼᴟᴒⱱꞌᴒᴐᴡᴒᴑͼ꞉ꜜͼ
ᴡⱳᴒͼᴠᴢꜛꜛԜᴟᴦͼꜝⱱͼᴐⱳԜꜜⱲᴒᴠ᷅
Summary of Changes from Previous Version
Protocol Amendments
Summary of Change(s) Since Last Version of Approved Protocol
Amendment Number
3.0
Amendment Date
09 Jan 2017
Global/Country/Site 
Specific
Global
Description and Rationale for Change
Section(s) Affected by 
Change
ᴂꜞᴑԜᴡᴒᴑͼԜᴑꜛ꞉ꜜ꞉ᴠᴡᴟԜᴡ꞉ᴣᴒͼ꞉ꜜⱱꜝᴟꜛԜᴡ꞉ꜝꜜͼᴡꜝͼᴟᴒⱱꞌᴒᴐᴡͼᴐᴢᴟᴟᴒꜜᴡͼᴐꜝꜜᴡԜᴐᴡͼ꞉ꜜⱱꜝᴟꜛԜᴡ꞉ꜝꜜⱱꜝᴟͼᴡⱳᴒ
ᴀꜞꜝꜜᴠꜝᴟᶳᴠͼꜚᴒᴑ꞉ᴐԜꞌͼꜚꜝꜜ꞉ᴡꜝᴟͼ ⱱꜝᴟͼⱬᴢᴟꜝꜞᴒͼԜꜜᴑͼꜗꜝᴟᴑԜꜜᴡꜝͼ
ԓͼꜚⱫ
ᴁ꞉ᴡꞌᴒͼ͟ԜⱲᴒԓͼᴀᴒᴐᴡ꞉ꜝꜜͼ᷈᷇
ᴀᴡᴢᴑᴦͼⱨᴑꜛ꞉ꜜ꞉ᴠᴡᴟԜᴡ꞉ᴣᴒͼ
ᴀᴡᴟᴢᴐᴡᴢᴟᴒ
ᴀꜞᴒᴐ꞉ⱱ꞉ᴒᴑͼᴡⱳԜᴡͼⱫᴦԜᴥͼⱪꜝᴟꜞͼ꞉ᴠͼԜꜜͼ꞉ꜜᴑ꞉ᴟᴒᴐᴡԓͼᴤⱳꜝꞌꞌᴦ᷄ꜝᴤꜜᴒᴑͼᴠᴢԝᴠ꞉ᴑ꞉Ԝᴟᴦͼꜝⱱͼᴀⱳ꞉ᴟᴒͼꜞꞌᴐ᷅
ᴁ꞉ᴡꞌᴒͼ͟ԜⱲᴒԓ ᴀᴡᴢᴑᴦͼᴀᴦꜜꜝꜞᴠ꞉ᴠԓͼ
ᴀᴒᴐᴡ꞉ꜝꜜͼ᷈᷇
ⱪꞌԜᴟ꞉ⱱ꞉ᴒᴑͼᴡⱳԜᴡͼꜞᴟ꞉ꜛԜᴟᴦͼԜꜜᴑͼᴠᴒᴐꜝꜜᴑԜᴟᴦͼᴒⱱⱱ꞉ᴐԜᴐᴦͼᴒꜜᴑꜞꜝ꞉ꜜᴡᴠͼᴤ꞉ꞌꞌͼԝᴒͼԝԜᴠᴒᴑͼꜝꜜͼԜꜜͼ
ᴒⱱⱱ꞉ᴐԜᴐᴦͼᴒᴣԜꞌᴢԜᴡ꞉ꜝꜜͼꜞᴒᴟ꞉ꜝᴑͼᴠꜞԜꜜꜜ꞉ꜜⱲͼⱫԜᴦͼ᷇ͼ(after study drug administrationԐͼ
ᴡⱳᴟꜝᴢⱲⱳͼⱫԜᴦͼ᷈˲᷉ԓ unless otherwise specified᷅ͼ
ᴀᴡᴢᴑᴦͼᴀᴦꜜꜝꜞᴠ꞉ᴠԓͼᴀᴒᴐᴡ꞉ꜝꜜͼ
⅍᷅᷾᷅᷈
ᴀꜞᴒᴐ꞉ⱱ꞉ᴒᴑͼᴡⱳԜᴡͼꜞᴟ꞉ꜛԜᴟᴦͼԜꜜᴑ᷈ᴠᴡԜꜜᴑͼ᷉ꜜᴑᴟԜꜜꞋͼꜝᴟᴑᴒᴟᴒᴑͼᴠᴒᴐꜝꜜᴑԜᴟᴦͼᴒⱱⱱ꞉ᴐԜᴐᴦͼᴒꜜᴑꜞꜝ꞉ꜜᴡᴠͼ
ᴤ꞉ꞌꞌͼԝᴒͼԜᴠᴠᴒᴠᴠᴒᴑͼduring the efficacy evaluation period (Day 0 through Day 
182) ᴡꜝͼԝᴒͼᴐꜝꜜᴠ꞉ᴠᴡᴒꜜᴡͼᴤ꞉ᴡⱳͼꜝᴡⱳᴒᴟͼᴠᴒᴐᴡ꞉ꜝꜜᴠͼӿᴀᴒᴐᴡ꞉ꜝꜜᴠͼⱠ᷅˲᷅᷈ͼԜꜜᴑͼⱠ᷅˲᷅᷉᷄ⱨꜜԜꞌᴦᴠ꞉ᴠͼꜝⱱͼ
͟ᴟ꞉ꜛԜᴟᴦͼԜꜜᴑͼᴀᴒᴐꜝꜜᴑԜᴟᴦͼⱬⱱⱱ꞉ᴐԜᴐᴦͼⱬꜜᴑꜞꜝ꞉ꜜᴡᴠԐ᷅
ᴀᴡᴢᴑᴦͼᴀᴦꜜꜝꜞᴠ꞉ᴠԓͼᴀᴒᴐᴡ꞉ꜝꜜͼ
⅍᷅᷾᷅᷈ԓ ᴀᴒᴐᴡ꞉ꜝꜜͼⱠ᷅˲᷅᷉
ⱨᴑᴑᴒᴑͼᴒⱱⱱ꞉ᴐԜᴐᴦͼꜛᴒԜᴠᴢᴟᴒͼᴡꜝͼԜᴠᴠᴒᴠᴠͼᴡⱳᴒͼꜜᴢꜛԝᴒᴟͼꜝⱱͼⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟ᷄ᴐꜝꜜⱱ꞉ᴟꜛᴒᴑͼⱶⱨⱬͼ
ԜᴡᴡԜᴐꞋᴠͼꜝᴐᴐᴢᴟᴟ꞉ꜜⱲͼꜝꜜͼⱫԜᴦͼ᷈᷾ͼᴡⱳᴟꜝᴢⱲⱳͼⱫԜᴦͼ᷈˲᷉ͼᴡꜝͼᴟԜꜜꞋͼꜝᴟᴑᴒᴟᴒᴑͼᴠᴒᴐꜝꜜᴑԜᴟᴦͼᴒⱱⱱ꞉ᴐԜᴐᴦͼ
ᴒꜜᴑꜞꜝ꞉ꜜᴡᴠͼⱱꜝᴟͼ꞉ꜜᴐꞌᴢᴠ꞉ꜝꜜͼ꞉ꜜͼᴡⱳᴒͼꜛᴢꞌᴡ꞉ꜞꞌᴒͼᴡᴒᴠᴡ꞉ꜜⱲͼꜞᴟꜝᴐᴒᴑᴢᴟᴒӿᴡⱳ꞉ᴟᴑ꞉ꜜͼᴡⱳᴒͼᴟԜꜜꞋͼꜝᴟᴑᴒᴟԐͼ
ᴡꜝͼԝᴒᴡᴡᴒᴟͼᴢꜜᴑᴒᴟᴠᴡԜꜜᴑͼᴡⱳᴒͼᴒᴥꜞꜝᴠᴢᴟᴒ᷄ᴟᴒᴠꜞꜝꜜᴠᴒͼᴟᴒꞌԜᴡ꞉ꜝꜜᴠⱳ꞉ꜞͼᴠ꞉ꜜᴐᴒͼᴑԜᴡԜͼⱱᴟꜝꜛͼ͟ⱳԜᴠᴒͼ᷈ԝͼ
ᴠᴡᴢᴑᴦͼӿⱫᴅ᷉Ⱡ᷊᷇᷄᷇᷉ԐͼᴠᴢⱲⱲᴒᴠᴡᴒᴑͼᴡⱳԜᴡͼꞌԜꜜԜᴑᴒꞌᴢꜛԜԝͼⱳԜᴠͼԜͼꜛᴒԜꜜͼᴒꞌ꞉ꜛ꞉ꜜԜᴡ꞉ꜝꜜͼⱳԜꞌⱱ᷄ꞌ꞉ⱱᴒͼ
ꜝⱱͼԜꜞꜞᴟꜝᴥ꞉ꜛԜᴡᴒꞌᴦͼ᷈᷾ͼᴑԜᴦᴠͼᴤⱳᴒᴟᴒͼ꞉ᴡͼ꞉ᴠͼԜꜜᴡ꞉ᴐ꞉ꜞԜᴡᴒᴑͼᴡⱳԜᴡͼ᷿᷇ӼͼᴠᴡᴒԜᴑᴦͼᴠᴡԜᴡᴒͼ꞉ᴠͼԜᴐⱳ꞉ᴒᴣᴒᴑͼ
꞉ꜜͼⱶⱨⱬͼᴠᴢԝ꞊ᴒᴐᴡᴠͼԜꜜᴑͼꞌԜꜜԜᴑᴒꞌᴢꜛԜԝͼᴒᴥꜞꜝᴠᴢᴟᴒͼᴟᴒԜᴐⱳᴒᴠͼᴟᴒԜᴠꜝꜜԜԝꞌᴒͼꞌᴒᴣᴒꞌᴠͼԜᴠᴠꜝᴐ꞉Ԝᴡᴒᴑͼ
ᴤ꞉ᴡⱳͼᴡⱳᴒᴟԜꜞᴒᴢᴡ꞉ᴐͼᴒⱱⱱᴒᴐᴡ᷅ͼ
ᴀᴡᴢᴑᴦͼᴀᴦꜜꜝꜞᴠ꞉ᴠԓͼᴀᴒᴐᴡ꞉ꜝꜜͼ
⅍᷅᷾᷅᷈ԓͼᴀᴒᴐᴡ꞉ꜝꜜͼⱠ᷅˲᷅᷉
ϸᴒꜛꜝᴣᴒᴑͼ꞉ꜜᴐꜝᴟᴟᴒᴐᴡͼᴐꜝꜜᴡԜᴐᴡͼ꞉ꜜⱱꜝᴟꜛԜᴡ꞉ꜝꜜͼꜞᴟꜝᴣ꞉ᴑᴒᴑͼⱱꜝᴟͼ᷉᷾᷄ⱳꜝᴢᴟͼꜛᴒᴑ꞉ᴐԜꞌͼᴠԜⱱᴒᴡᴦͼ
ᴀᴒᴐᴡ꞉ꜝꜜͼ⅍᷅᷈⅍᷿᷿᷅᷅
PPD

Ⱬᴅ᷄᷉Ⱡ᷊᷇
ⱪꞌ꞉ꜜ꞉ᴐԜꞌͼᴁᴟ꞉Ԝꞌͼ͟ᴟꜝᴡꜝᴐꜝꞌⱡͼⱫᴅ᷄᷉Ⱡ᷊᷊᷇᷄᷇
ⱨꜛᴒꜜᴑꜛᴒꜜᴡͼ᷊᷅᷇ⱴ꞉ꜜԜꞌⱡͼ᷇ⱠͼꜗԜꜜᴢԜᴟᴦ᷉᷇᷈ⅎ
ⱪꜝꜜⱱ꞉ᴑᴒꜜᴡ꞉Ԝꞌ
͟ԜⱲᴒͼ᷾
ⱫᴦԜᴥͼⱪꜝᴟꜞ᷅
Protocol Amendments
Summary of Change(s) Since Last Version of Approved Protocol
Amendment Number
3.0
Amendment Date
09 Jan 2017
Global/Country/Site 
Specific
Global
Description and Rationale for Change
Section(s) Affected by 
Change
ᴐꜝꜜᴡԜᴐᴡͼⱱꜝᴟͼᴂᴀԓͼⱪԜꜜԜᴑԜԓͼⱬᴢᴟꜝꜞᴒԓͼԜꜜᴑͼꜚ꞉ᴑᴑꞌᴒͼⱬԜᴠᴡ᷅ͼ
ᴂꜞᴑԜᴡᴒᴑͼᴡⱳᴒͼꜛᴢꞌᴡ꞉ꜞꞌ꞉ᴐ꞉ᴡᴦͼꜞᴟꜝᴐᴒᴑᴢᴟᴒͼԝᴦͼԜᴑᴑ꞉ꜜⱲͼᴡⱳᴒͼᶰⱴԜꜛ꞉ꞌᴦͼ᷾ͼӿⱴ᷾Ԑᶱͼⱳᴦꜞꜝᴡⱳᴒᴠ꞉ᴠͼᴡᴒᴠᴡͼ
ᴡꜝͼᴡⱳᴒͼ᷊᷄ԝᴟԜꜜᴐⱳͼⱲᴒꜜᴒᴟԜꞌͼⱲԜᴡᴒꞋᴒᴒꜞ꞉ꜜⱲͼꜞᴟꜝᴐᴒᴑᴢᴟᴒͼӿꜞᴟᴒᴣ꞉ꜝᴢᴠꞌᴦͼᴤ꞉ᴡⱳͼ᷊ͼⱱԜꜛ꞉ꞌ꞉ᴒᴠͼꜝⱱͼ
ⱳᴦꜞꜝᴡⱳᴒᴠᴒᴠԐͼⱱꜝᴟͼᴡⱳᴒͼᴡⱳ꞉ᴟᴑͼᴟԜꜜꞋᴒᴑͼᴠᴒᴐꜝꜜᴑԜᴟᴦͼᴒⱱⱱ꞉ᴐԜᴐᴦͼᴒꜜᴑꜞꜝ꞉ꜜᴡ᷅ͼͼ
ᴀᴒᴐᴡ꞉ꜝꜜⱠ᷿᷅᷈᷉᷅
ϸᴒꜞꞌԜᴐᴒᴑͼᴡⱳᴒͼᴡԜԝꞌᴒͼⱱꜝᴟͼᴡⱳᴒͼᴠᴡᴢᴑᴦͼԜᴐᴡ꞉ᴣ꞉ᴡ꞉ᴒᴠͼᴠᴐⱳᴒᴑᴢꞌᴒͼӿԜͼᴟᴒꜞᴒᴡ꞉ᴡ꞉ꜝꜜԐͼ꞉ꜜͼⱨꜞꜞᴒꜜᴑ꞉ᴥͼ᷈ͼ
ᴤ꞉ᴡⱳͼᴡⱳᴒͼ͟ᴟꜝᴡꜝᴐꜝꞌͼⱶ꞉ᴠᴡꜝᴟᴦ᷅ͼ꜠ᴢꜛԝᴒᴟᴒᴑͼᴡⱳᴒͼᴡԜԝꞌᴒͼⱱꜝᴟͼᴡⱳᴒͼᴠᴡᴢᴑᴦͼԜᴐᴡ꞉ᴣ꞉ᴡ꞉ᴒᴠͼᴠᴐⱳᴒᴑᴢꞌᴒͼ
ӿᴡⱳԜᴡͼⱱꜝꞌꞌꜝᴤᴠͼᴡⱳᴒͼᴀᴡᴢᴑᴦͼᴀᴦꜜꜝꜞᴠ꞉ᴠԐͼԜᴠͼᴁԜԝꞌᴒͼ᷈᷅ͼϸᴒꜛꜝᴣᴒᴑͼᴐᴟꜝᴠᴠ᷄ᴟᴒⱱᴒᴟᴒꜜᴐᴒͼᴡꜝͼᴡⱳᴒͼ
ᴡᴟᴒԜᴡꜛᴒꜜᴡͼꜞᴒᴟ꞉ꜝᴑͼᴑꜝᴠ꞉ꜜⱲͼᴠᴐⱳᴒᴑᴢꞌᴒͼ꞉ꜜͼᴡⱳᴒͼᴀᴡᴢᴑᴦͼᴀᴦꜜꜝꜞᴠ꞉ᴠ᷅
ᴀᴒᴐᴡ꞉ꜝꜜͼ᷈᷉ԓͼⱨꜞꜞᴒꜜᴑ꞉ᴥͼ᷈
ᴀᴡᴢᴑᴦͼⱨᴐᴡ꞉ᴣ꞉ᴡ꞉ᴒᴠͼᴀᴐⱳᴒᴑᴢꞌᴒԓͼ
ᴀᴡᴢᴑᴦͼᴀᴦꜜꜝꜞᴠ꞉ᴠ᷅

Ⱬᴅ᷄᷉Ⱡ᷊᷇
ⱪꞌ꞉ꜜ꞉ᴐԜꞌͼᴁᴟ꞉Ԝꞌͼ͟ᴟꜝᴡꜝᴐꜝꞌⱡͼⱫᴅ᷄᷉Ⱡ᷊᷊᷇᷄᷇
ⱨꜛᴒꜜᴑꜛᴒꜜᴡͼ᷊᷅᷇ⱴ꞉ꜜԜꞌⱡͼ᷇ⱠͼꜗԜꜜᴢԜᴟᴦ᷉᷇᷈ⅎ
ⱪꜝꜜⱱ꞉ᴑᴒꜜᴡ꞉Ԝꞌ
͟ԜⱲᴒͼ᷿
ⱫᴦԜᴥͼⱪꜝᴟꜞ᷅
SYNOPSIS
Sponsor:
ⱫᴦԜᴥⱪꜝᴟꜞ᷅ԓͼԜꜜͼ꞉ꜜᴑ꞉ᴟᴒᴐᴡԓͼᴤⱳꜝꞌꞌᴦ᷄ꜝᴤꜜᴒᴑͼᴠᴢԝᴠ꞉ᴑ꞉Ԝᴟᴦͼꜝⱱͼᴀⱳ꞉ᴟᴒͼꜞꞌᴐ
᷿᷿ͼ꜠ᴒᴡᴤꜝᴟꞋͼⱫᴟ꞉ᴣᴒԓͼⱩᴢᴟꞌ꞉ꜜⱲᴡꜝꜜԓͼꜚⱨͼ᷇᷈˲᷊᷇ͼᴂᴀⱨ
Name of Finished Product:
Ⱬᴅ᷄᷉Ⱡ᷊᷇ͼⱫᴟᴢⱲͼ͟ᴟꜝᴑᴢᴐᴡͼӿⱫ͟Ԑ
Name of Active Ingredient:
Ⱬᴅ᷄᷉Ⱡ᷊᷇ͼ꞉ᴠͼԜͼᴟᴒᴐꜝꜛԝ꞉ꜜԜꜜᴡԓͼⱪⱳ꞉ꜜᴒᴠᴒͼⱳԜꜛᴠᴡᴒᴟͼꜝᴣԜᴟᴦͼӿⱪⱶ꜡Ԑͼᴐᴒꞌꞌ᷄ᴒᴥꜞᴟᴒᴠᴠᴒᴑԓͼⱱᴢꞌꞌᴦͼⱳᴢꜛԜꜜͼ
꞉ꜛꜛᴢꜜꜝⱲꞌꜝԝᴢꞌ꞉ꜜͼⱵͼᴠᴢԝᴐꞌԜᴠᴠͼ᷈ͼӿⱷⱲⱵ᷈ԐԓͼꞋԜꜞꜞԜͼꞌ꞉ⱲⱳᴡͼᴐⱳԜ꞉ꜜԓͼꜛꜝꜜꜝᴐꞌꜝꜜԜꞌͼԜꜜᴡ꞉ԝꜝᴑᴦ᷅
Names of Inactive Ingredients:
ᴀꜝᴑ꞉ᴢꜛͼꜞⱳꜝᴠꜞⱳԜᴡᴒͼᴑ꞉ԝԜᴠ꞉ᴐͼᴑ꞉ⱳᴦᴑᴟԜᴡᴒԓͼᴐ꞉ᴡᴟ꞉ᴐͼԜᴐ꞉ᴑͼꜛꜝꜜꜝⱳᴦᴑᴟԜᴡᴒԓͼꜙ᷄ⱳ꞉ᴠᴡ꞉ᴑ꞉ꜜᴒԓͼᴠꜝᴑ꞉ᴢꜛͼᴐⱳꞌꜝᴟ꞉ᴑᴒԓͼ
Ԝꜜᴑͼ͟ꜝꞌᴦᴠꜝᴟԝԜᴡᴒͼ˲᷇
Study Title:
ⱶⱬꜙ͟ͼᴀᴡᴢᴑᴦᴁꜚⱡͼⱨͼꜚᴢꞌᴡ꞉ᴐᴒꜜᴡᴒᴟԓͼϸԜꜜᴑꜝꜛ꞉ᴧᴒᴑԓͼⱫꜝᴢԝꞌᴒ᷄Ⱪꞌ꞉ꜜᴑԓͼ͟ꞌԜᴐᴒԝꜝ᷄ⱪꜝꜜᴡᴟꜝꞌꞌᴒᴑͼⱬⱱⱱ꞉ᴐԜᴐᴦͼԜꜜᴑͼ
ᴀԜⱱᴒᴡᴦͼᴀᴡᴢᴑᴦͼᴡꜝͼⱬᴣԜꞌᴢԜᴡᴒͼⱫᴅ᷄᷉Ⱡ᷊᷇ͼⱴꜝᴟͼꜙꜝꜜⱲ᷄ᴁᴒᴟꜛͼ͟ᴟꜝꜞⱳᴦꞌԜᴥ꞉ᴠͼⱨⱲԜ꞉ꜜᴠᴡͼⱨᴐᴢᴡᴒͼⱨᴡᴡԜᴐꞋᴠͼꜝⱱͼ
ⱶᴒᴟᴒᴑ꞉ᴡԜᴟᴦͼⱨꜜⱲ꞉ꜝᴒᴑᴒꜛԜͼӿⱶⱨⱬԐ
Study Number:
Ⱬᴅ᷄᷉Ⱡ᷊᷊᷇᷄᷇
Study Phase: ͟ⱳԜᴠᴒͼ᷊
Study Location:
ⱨꜞꜞᴟꜝᴥ꞉ꜛԜᴡᴒꞌᴦͼ⅍᷇ͼᴠᴡᴢᴑᴦͼᴠ꞉ᴡᴒᴠͼꜞꞌԜꜜꜜᴒᴑͼԜᴐᴟꜝᴠᴠͼᴡⱳᴒͼᴂꜜ꞉ᴡᴒᴑͼᴀᴡԜᴡᴒᴠԓͼⱷᴡԜꞌᴦԓͼᴂꜜ꞉ᴡᴒᴑͼꜘ꞉ꜜⱲᴑꜝꜛԓͼ
ⱵᴒᴟꜛԜꜜᴦԓͼⱪԜꜜԜᴑԜͼԜꜜᴑͼꜗꜝᴟᴑԜꜜ
Primary Objective:
ᴁꜝͼᴒᴣԜꞌᴢԜᴡᴒͼᴡⱳᴒͼᴒⱱⱱ꞉ᴐԜᴐᴦͼꜝⱱͼⱫᴅ᷄᷉Ⱡ᷊᷇ͼ꞉ꜜͼꜞᴟᴒᴣᴒꜜᴡ꞉ꜜⱲͼⱶⱨⱬͼԜᴡᴡԜᴐꞋᴠ
Secondary Objective:
ᴁꜝͼᴒᴣԜꞌᴢԜᴡᴒͼᴡⱳᴒͼᴠԜⱱᴒᴡᴦͼꜝⱱͼᴟᴒꜞᴒԜᴡᴒᴑͼᴠᴢԝᴐᴢᴡԜꜜᴒꜝᴢᴠͼԜᴑꜛ꞉ꜜ꞉ᴠᴡᴟԜᴡ꞉ꜝꜜᴠͼꜝⱱͼⱫᴅ᷄᷉Ⱡ᷊᷇
Tertiary Objectives:
ᶄ
ᴁꜝͼᴒᴣԜꞌᴢԜᴡᴒͼᴡⱳᴒͼꜞⱳԜᴟꜛԜᴐꜝᴑᴦꜜԜꜛ꞉ᴐͼӿ͟ⱫԐͼᴒⱱⱱᴒᴐᴡᴠͼꜝⱱͼᴐⱳᴟꜝꜜ꞉ᴐԜꞌꞌᴦͼԜᴑꜛ꞉ꜜ꞉ᴠᴡᴒᴟᴒᴑͼⱫᴅ᷄᷉Ⱡ᷊᷇
ᶄ
ᴁꜝͼԜᴠᴠᴒᴠᴠͼᴡⱳᴒͼ꞉ꜛꜛᴢꜜꜝⱲᴒꜜ꞉ᴐ꞉ᴡᴦͼꜝⱱͼᴐⱳᴟꜝꜜ꞉ᴐԜꞌꞌᴦͼԜᴑꜛ꞉ꜜ꞉ᴠᴡᴒᴟᴒᴑͼⱫᴅ᷄᷉Ⱡ᷊᷇
ᶄ
ᴁꜝͼᴒᴣԜꞌᴢԜᴡᴒͼᴡⱳᴒͼꜞⱳԜᴟꜛԜᴐꜝꞋ꞉ꜜᴒᴡ꞉ᴐᴠͼӿ͟ꜘԐͼꜝⱱͼᴐⱳᴟꜝꜜ꞉ᴐԜꞌꞌᴦͼԜᴑꜛ꞉ꜜ꞉ᴠᴡᴒᴟᴒᴑͼⱫᴅ᷄᷉Ⱡ᷊᷇
ᶄ
ᴁꜝͼᴒᴣԜꞌᴢԜᴡᴒͼᴡⱳᴒͼᴒⱱⱱᴒᴐᴡͼꜝⱱͼⱫᴅ᷄᷉Ⱡ᷊᷇ͼꜝꜜͼⱳᴒԜꞌᴡⱳ᷄ᴟᴒꞌԜᴡᴒᴑͼꜟᴢԜꞌ꞉ᴡᴦͼꜝⱱͼꞌ꞉ⱱᴒͼӿϷꜝꜙԐ
Study Design:
ᴁⱳ꞉ᴠͼᴠᴡᴢᴑᴦͼ꞉ᴠͼԜͼꜞⱳԜᴠᴒͼ᷊ԓͼꜛᴢꞌᴡ꞉ᴐᴒꜜᴡᴒᴟԓͼᴟԜꜜᴑꜝꜛ꞉ᴧᴒᴑԓͼᴑꜝᴢԝꞌᴒ᷄ԝꞌ꞉ꜜᴑԓͼꜞꞌԜᴐᴒԝꜝ᷄ᴐꜝꜜᴡᴟꜝꞌꞌᴒᴑͼᴡᴟ꞉Ԝꞌͼᴡꜝͼ
ᴒᴣԜꞌᴢԜᴡᴒͼᴡⱳᴒͼᴒⱱⱱ꞉ᴐԜᴐᴦͼԜꜜᴑͼᴠԜⱱᴒᴡᴦͼꜝⱱͼⱫᴅ᷄᷉Ⱡ᷊᷇ͼ꞉ꜜͼꜞᴟᴒᴣᴒꜜᴡ꞉ꜜⱲͼԜᴐᴢᴡᴒͼԜꜜⱲ꞉ꜝᴒᴑᴒꜛԜͼԜᴡᴡԜᴐꞋᴠͼ꞉ꜜͼ

Ⱬᴅ᷄᷉Ⱡ᷊᷇
ⱪꞌ꞉ꜜ꞉ᴐԜꞌͼᴁᴟ꞉Ԝꞌͼ͟ᴟꜝᴡꜝᴐꜝꞌⱡͼⱫᴅ᷄᷉Ⱡ᷊᷊᷇᷄᷇
ⱨꜛᴒꜜᴑꜛᴒꜜᴡͼ᷊᷅᷇ⱴ꞉ꜜԜꞌⱡͼ᷇ⱠͼꜗԜꜜᴢԜᴟᴦ᷉᷇᷈ⅎ
ⱪꜝꜜⱱ꞉ᴑᴒꜜᴡ꞉Ԝꞌ
͟ԜⱲᴒͼ⅍
ⱫᴦԜᴥͼⱪꜝᴟꜞ᷅
ꜞԜᴡ꞉ᴒꜜᴡᴠͼᴤ꞉ᴡⱳͼᴁᴦꜞᴒͼⱷͼԜꜜᴑͼᴁᴦꜞᴒͼⱷⱷͼⱶⱨⱬ᷅
ꜙꜝꜜⱲ᷄ᴁᴒᴟꜛͼ͟ᴟꜝꜞⱳᴦꞌԜᴐᴡ꞉ᴐͼӿꜙᴁ͟ԐͼᴁⱳᴒᴟԜꜞᴦͼᴄԜᴠⱳꜝᴢᴡⱡ
ⱴꜝꞌꞌꜝᴤ꞉ꜜⱲͼ꞉ꜜⱱꜝᴟꜛᴒᴑͼᴐꜝꜜᴠᴒꜜᴡԓͼᴠᴢԝ꞊ᴒᴐᴡᴠͼᴤ꞉ꞌꞌͼᴢꜜᴑᴒᴟⱲꜝͼᴠᴐᴟᴒᴒꜜ꞉ꜜⱲͼԜᴠᴠᴒᴠᴠꜛᴒꜜᴡᴠ᷅ͼᴀᴐᴟᴒᴒꜜᴒᴑͼᴠᴢԝ꞊ᴒᴐᴡᴠͼ
ᴤⱳꜝͼԜᴟᴒͼꜝꜜͼꞌꜝꜜⱲ᷄ᴡᴒᴟꜛͼꜞᴟꜝꜞⱳᴦꞌԜᴐᴡ꞉ᴐͼᴡⱳᴒᴟԜꜞᴦͼⱱꜝᴟͼⱶⱨⱬͼԜᴟᴒͼᴟᴒꜟᴢ꞉ᴟᴒᴑͼᴡꜝͼᴢꜜᴑᴒᴟⱲꜝͼԜͼꜛ꞉ꜜ꞉ꜛᴢꜛͼ
᷉ᴤᴒᴒꞋͼᴤԜᴠⱳꜝᴢᴡͼꜞᴒᴟ꞉ꜝᴑͼꜞᴟ꞉ꜝᴟͼᴡꜝͼᴡⱳᴒͼᴠᴡԜᴟᴡͼꜝⱱͼᴡⱳᴒͼᴟᴢꜜ᷄꞉ꜜͼꜞᴒᴟ꞉ꜝᴑ᷅ͼᴁⱳ꞉ᴠͼꜙᴁ͟ͼᴤԜᴠⱳꜝᴢᴡͼ꞉ᴠͼꜞᴒᴟꜛ꞉ᴡᴡᴒᴑͼ
ԜᴠͼꞌꜝꜜⱲͼԜᴠͼᴡⱳᴒͼⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟͼᴑᴒᴡᴒᴟꜛ꞉ꜜᴒᴠͼᴡⱳԜᴡͼᴑꜝ꞉ꜜⱲͼᴠꜝͼᴤꜝᴢꞌᴑͼꜜꜝᴡͼꜞꞌԜᴐᴒͼᴡⱳᴒͼᴠᴢԝ꞊ᴒᴐᴡͼԜᴡͼԜꜜᴦͼᴢꜜᴑᴢᴒͼ
ᴠԜⱱᴒᴡᴦͼᴟ꞉ᴠꞋͼԜꜜᴑͼᴡⱳᴒͼᴠᴢԝ꞊ᴒᴐᴡͼ꞉ᴠͼԜᴡͼꞌᴒԜᴠᴡͼ᷈˲ͼᴦᴒԜᴟᴠͼꜝⱱͼԜⱲᴒ᷅ͼᴁⱳᴒͼⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟͼꜛᴢᴠᴡͼᴐꜝꜜⱱ꞉ᴟꜛͼᴡⱳᴒͼ
ᴠᴢԝ꞊ᴒᴐᴡͼⱳԜᴠͼᴠᴢᴐᴐᴒᴠᴠⱱᴢꞌꞌᴦͼᴐꜝꜛꜞꞌᴒᴡᴒᴑͼᴡⱳᴒͼ᷉ͼᴤᴒᴒꞋͼᴤԜᴠⱳꜝᴢᴡͼꜞᴒᴟ꞉ꜝᴑͼԝᴒⱱꜝᴟᴒͼᴡⱳᴒᴦͼᴐԜꜜͼᴒꜜᴡᴒᴟͼᴡⱳᴒͼᴟᴢꜜ᷄
꞉ꜜͼꜞᴒᴟ꞉ꜝᴑ᷅
ϸᴢꜜ᷄ⱷꜜͼ͟ᴒᴟ꞉ꜝᴑⱡ
ᴀᴐᴟᴒᴒꜜᴒᴑͼᴠᴢԝ꞊ᴒᴐᴡᴠͼᴤⱳꜝͼԜᴟᴒͼᴒ꞉ᴡⱳᴒᴟͼꜜꜝᴡͼꜝꜜͼꞌꜝꜜⱲ᷄ᴡᴒᴟꜛͼꜞᴟꜝꜞⱳᴦꞌԜᴐᴡ꞉ᴐͼᴡⱳᴒᴟԜꜞᴦͼⱱꜝᴟͼⱶⱨⱬԓͼꜝᴟͼⱳԜᴣᴒͼ
ᴐꜝꜛꜞꞌᴒᴡᴒᴑͼᴡⱳᴒͼᴟᴒꜟᴢ꞉ᴟᴒᴑͼᴤԜᴠⱳꜝᴢᴡͼꜞᴒᴟ꞉ꜝᴑԓͼᴤ꞉ꞌꞌͼᴒꜜᴡᴒᴟͼԜͼᴟᴢꜜ᷄꞉ꜜͼꜞᴒᴟ꞉ꜝᴑͼꜝⱱͼ᷾ͼᴤᴒᴒꞋᴠͼᴡꜝͼᴑᴒᴡᴒᴟꜛ꞉ꜜᴒͼᴡⱳᴒͼ
ԝԜᴠᴒꞌ꞉ꜜᴒͼⱶⱨⱬͼԜᴡᴡԜᴐꞋͼᴟԜᴡᴒ᷅ͼ꜡ꜜꞌᴦͼᴠᴢԝ꞊ᴒᴐᴡᴠͼꜛᴒᴒᴡ꞉ꜜⱲͼԜͼꜛ꞉ꜜ꞉ꜛᴢꜛͼԝԜᴠᴒꞌ꞉ꜜᴒͼᴟԜᴡᴒͼꜝⱱͼԜᴡͼꞌᴒԜᴠᴡͼ
᷈ⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟ᷄ᴐꜝꜜⱱ꞉ᴟꜛᴒᴑͼⱶⱨⱬͼԜᴡᴡԜᴐꞋͼꜞᴒᴟͼ᷾ͼᴤᴒᴒꞋᴠͼᴤ꞉ꞌꞌͼԝᴒͼᴒꞌ꞉Ⱳ꞉ԝꞌᴒͼⱱꜝᴟͼᴒꜜᴟꜝꞌꞌꜛᴒꜜᴡͼԜꜜᴑͼ
ᴟԜꜜᴑꜝꜛ꞉ᴧԜᴡ꞉ꜝꜜ᷅ͼᴀᴢԝ꞊ᴒᴐᴡᴠͼᴤⱳꜝͼᴒᴥꜞᴒᴟ꞉ᴒꜜᴐᴒͼ᷊ͼꜝᴟͼꜛꜝᴟᴒͼⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟ᷄ᴐꜝꜜⱱ꞉ᴟꜛᴒᴑͼԜᴡᴡԜᴐꞋᴠͼԝᴒⱱꜝᴟᴒͼᴡⱳᴒͼ
ᴒꜜᴑͼꜝⱱͼᴡⱳᴒͼ᷾ͼᴤᴒᴒꞋᴠͼᴐԜꜜͼᴒᴥ꞉ᴡͼᴡⱳᴒͼᴟᴢꜜ᷄꞉ꜜͼꜞᴒᴟ꞉ꜝᴑͼᴒԜᴟꞌᴦͼԜꜜᴑͼꜞᴟꜝᴐᴒᴒᴑͼᴡꜝͼᴒꜜᴟꜝꞌꞌꜛᴒꜜᴡͼԜꜜᴑͼ
ᴟԜꜜᴑꜝꜛ꞉ᴧԜᴡ꞉ꜝꜜ᷅ͼᴀᴢԝ꞊ᴒᴐᴡᴠͼᴤ꞉ᴡⱳꜝᴢᴡͼԜᴡͼꞌᴒԜᴠᴡͼ᷈ͼⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟ᷄ᴐꜝꜜⱱ꞉ᴟꜛᴒᴑͼԜᴡᴡԜᴐꞋͼԜⱱᴡᴒᴟͼ᷾ͼᴤᴒᴒꞋᴠͼꜝⱱͼᴟᴢꜜ᷄
꞉ꜜͼᴤ꞉ꞌꞌͼⱳԜᴣᴒͼᴡⱳᴒ꞉ᴟͼᴟᴢꜜ᷄꞉ꜜͼꜞᴒᴟ꞉ꜝᴑͼᴒᴥᴡᴒꜜᴑᴒᴑͼⱱꜝᴟͼԜꜜꜝᴡⱳᴒᴟͼ᷾ͼᴤᴒᴒꞋᴠԓͼᴑᴢᴟ꞉ꜜⱲͼᴤⱳ꞉ᴐⱳͼᴡ꞉ꜛᴒͼᴡⱳᴒᴦͼꜜᴒᴒᴑͼᴡꜝͼ
ⱳԜᴣᴒͼԜᴡͼꞌᴒԜᴠᴡͼ᷉ͼⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟ᷄ᴐꜝꜜⱱ꞉ᴟꜛᴒᴑͼԜᴡᴡԜᴐꞋᴠͼᴡꜝͼꜞᴟꜝᴐᴒᴒᴑͼᴡꜝͼᴒꜜᴟꜝꞌꞌꜛᴒꜜᴡͼԜꜜᴑͼᴟԜꜜᴑꜝꜛ꞉ᴧԜᴡ꞉ꜝꜜ᷅ͼ
ᴁꜝͼԝᴒͼᴒꞌ꞉Ⱳ꞉ԝꞌᴒͼⱱꜝᴟͼᴒꜜᴟꜝꞌꞌꜛᴒꜜᴡԓͼᴠᴢԝ꞊ᴒᴐᴡᴠͼᴤⱳꜝⱳԜᴣᴒͼᴡⱳᴒ꞉ᴟͼᴟᴢꜜ᷄꞉ꜜͼᴒᴥᴡᴒꜜᴑᴒᴑͼꜛᴢᴠᴡͼᴐꜝꜛꜞꞌᴒᴡᴒͼᴡⱳᴒͼⱱᴢꞌꞌͼ
˲᷄ᴤᴒᴒꞋͼᴟᴢꜜ᷄꞉ꜜͼꜞᴒᴟ꞉ꜝᴑͼꜞᴟ꞉ꜝᴟͼᴡꜝͼᴒꜜᴡᴒᴟ꞉ꜜⱲͼᴡⱳᴒͼᴡᴟᴒԜᴡꜛᴒꜜᴡͼꜞᴒᴟ꞉ꜝᴑ᷅ͼᴀᴢԝ꞊ᴒᴐᴡᴠͼᴤⱳꜝͼᴑꜝͼꜜꜝᴡͼꜛᴒᴒᴡͼᴡⱳᴒͼ
ꜛ꞉ꜜ꞉ꜛᴢꜛͼԜᴡᴡԜᴐꞋͼᴟԜᴡᴒͼᴑᴢᴟ꞉ꜜⱲͼᴟᴢꜜ᷄꞉ꜜͼꜝᴟͼԜᴟᴒͼꜝᴡⱳᴒᴟᴤ꞉ᴠᴒͼᴑᴒᴡᴒᴟꜛ꞉ꜜᴒᴑͼᴡꜝͼԝᴒͼ꞉ꜜᴒꞌ꞉Ⱳ꞉ԝꞌᴒͼᴑᴢᴒͼᴡꜝͼ
ᴠᴐᴟᴒᴒꜜ꞉ꜜⱲͼԜᴠᴠᴒᴠᴠꜛᴒꜜᴡᴠͼᴤ꞉ꞌꞌͼԝᴒᴐꜝꜜᴠ꞉ᴑᴒᴟᴒᴑͼᴠᴐᴟᴒᴒꜜͼⱱԜ꞉ꞌᴢᴟᴒᴠ᷅ͼᴀᴢԝ꞊ᴒᴐᴡᴠͼᴤⱳꜝͼᴠᴐᴟᴒᴒꜜͼⱱԜ꞉ꞌͼᴤ꞉ꞌꞌͼꜜꜝᴡͼԝᴒͼ
Ԝꞌꞌꜝᴤᴒᴑͼᴡꜝͼᴟᴒᴠᴐᴟᴒᴒꜜͼ꞉ꜜᴡꜝͼᴡⱳᴒͼᴠᴡᴢᴑᴦ᷅ͼ
ᴁᴟᴒԜᴡꜛᴒꜜᴡͼ͟ᴒᴟ꞉ꜝᴑⱡ
ⱨⱱᴡᴒᴟͼᴣᴒᴟ꞉ⱱ꞉ᴐԜᴡ꞉ꜝꜜͼꜝⱱͼᴒꞌ꞉Ⱳ꞉ԝ꞉ꞌ꞉ᴡᴦԓͼᴠᴢԝ꞊ᴒᴐᴡᴠͼᴤ꞉ꞌꞌͼԝᴒͼᴟԜꜜᴑꜝꜛ꞉ᴧᴒᴑͼ᷉ⱡ᷈ͼᴡꜝͼᴟᴒᴐᴒ꞉ᴣᴒͼᴟᴒꜞᴒԜᴡᴒᴑͼ
ᴠᴢԝᴐᴢᴡԜꜜᴒꜝᴢᴠͼӿᴀⱪԐͼԜᴑꜛ꞉ꜜ꞉ᴠᴡᴟԜᴡ꞉ꜝꜜᴠͼꜝⱱͼⱫᴅ᷄᷉Ⱡ᷊᷇ͼꜝᴟͼꜞꞌԜᴐᴒԝꜝͼ꞉ꜜͼԜͼᴑꜝᴢԝꞌᴒ᷄ԝꞌ꞉ꜜᴑͼⱱԜᴠⱳ꞉ꜝꜜ᷅ͼ
ᴀᴢԝ꞊ᴒᴐᴡᴠͼᴤⱳꜝͼԜᴟᴒͼᴟԜꜜᴑꜝꜛ꞉ᴧᴒᴑͼᴡꜝͼⱫᴅ᷄᷉Ⱡ᷊᷇ͼᴤ꞉ꞌꞌͼԝᴒͼԜᴠᴠ꞉Ⱳꜜᴒᴑͼ꞉ꜜͼԜͼ᷈ⱡ᷈ⱡ᷈ͼᴟԜᴡ꞉ꜝͼᴡꜝͼꜝꜜᴒͼꜝⱱͼᴡⱳᴟᴒᴒͼ
ᴑꜝᴠᴒͼᴟᴒⱲ꞉ꜛᴒꜜᴠⱡͼ᷊᷇᷇ͼꜛⱲͼᴒᴣᴒᴟᴦͼ᷉ͼᴤᴒᴒꞋᴠԓͼ᷊᷇᷇ͼꜛⱲͼᴒᴣᴒᴟᴦͼ᷾ͼᴤᴒᴒꞋᴠͼꜝᴟͼ᷿᷈᷇ͼꜛⱲͼᴒᴣᴒᴟᴦͼ᷾ͼᴤᴒᴒꞋᴠ᷅ͼ
ϸԜꜜᴑꜝꜛ꞉ᴧԜᴡ꞉ꜝꜜͼ꞉ꜜᴡꜝͼԜꞌꞌͼᴡᴟᴒԜᴡꜛᴒꜜᴡͼⱲᴟꜝᴢꜞᴠͼᴤ꞉ꞌꞌͼԝᴒͼᴠᴡᴟԜᴡ꞉ⱱ꞉ᴒᴑͼԝᴦͼᴡⱳᴒͼԝԜᴠᴒꞌ꞉ꜜᴒͼԜᴡᴡԜᴐꞋͼᴟԜᴡᴒͼꜝԝᴠᴒᴟᴣᴒᴑͼ
ᴑᴢᴟ꞉ꜜⱲͼᴡⱳᴒͼᴟᴢꜜ᷄꞉ꜜͼꜞᴒᴟ꞉ꜝᴑͼ꞉ꜜᴡꜝͼᴡⱳᴒͼⱱꜝꞌꞌꜝᴤ꞉ꜜⱲͼⱲᴟꜝᴢꜞᴠⱡͼ᷈ᴡꜝⱣ᷉ԜᴡᴡԜᴐꞋᴠͼꜞᴒᴟͼ᷾ͼᴤᴒᴒꞋᴠԓͼ᷉ͼᴡꜝͼⱣͼ᷊ͼ
ԜᴡᴡԜᴐꞋᴠͼꜞᴒᴟͼ᷾ͼᴤᴒᴒꞋᴠԓͼԜꜜᴑͼᶒͼ᷊ͼԜᴡᴡԜᴐꞋᴠͼꜞᴒᴟͼ᷾ͼᴤᴒᴒꞋᴠ᷅
ⱬԜᴐⱳͼᴠᴢԝ꞊ᴒᴐᴡͼᴤ꞉ꞌꞌͼᴢꜜᴑᴒᴟⱲꜝͼԜͼᴡᴟᴒԜᴡꜛᴒꜜᴡͼꜞᴒᴟ꞉ꜝᴑͼᴐꜝꜜᴠ꞉ᴠᴡ꞉ꜜⱲͼꜝⱱͼ᷊᷈ͼᴑꜝᴠᴒᴠͼꜝⱱͼԝꞌ꞉ꜜᴑᴒᴑͼ
ⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡ꞉ꜝꜜԜꞌͼꜚᴒᴑ꞉ᴐ꞉ꜜԜꞌͼ͟ᴟꜝᴑᴢᴐᴡͼӿⱷꜚ͟ԐԓͼⱱꜝᴟͼԜͼꜞᴒᴟ꞉ꜝᴑͼꜝⱱͼ᷉⅍ͼᴤᴒᴒꞋᴠͼⱱᴟꜝꜛͼᴡⱳᴒͼᴑԜᴡᴒͼꜝⱱͼⱱ꞉ᴟᴠᴡͼᴑꜝᴠᴒͼ
ꜝꜜͼⱫԜᴦͼ᷇ͼᴡⱳᴟꜝᴢⱲⱳͼᴡᴤꜝͼᴤᴒᴒꞋᴠͼԜⱱᴡᴒᴟͼᴡⱳᴒͼⱱ꞉ꜜԜꞌͼᴑꜝᴠᴒ᷅ͼᴀᴢԝ꞊ᴒᴐᴡᴠͼᴟԜꜜᴑꜝꜛ꞉ᴧᴒᴑͼᴡꜝͼꜝꜜᴒͼꜝⱱͼᴡⱳᴒͼ᷾ͼ
ᴡᴟᴒԜᴡꜛᴒꜜᴡͼԜᴟꜛᴠͼᴤ꞉ꞌꞌͼᴒ꞉ᴡⱳᴒᴟͼᴟᴒᴐᴒ꞉ᴣᴒͼԜͼⱫᴅ᷄᷉Ⱡ᷊᷇ͼꜝᴟͼꜞꞌԜᴐᴒԝꜝͼᴑꜝᴠᴒͼԜᴐᴐꜝᴟᴑ꞉ꜜⱲͼᴡꜝͼᴡⱳᴒͼᴑꜝᴠ꞉ꜜⱲͼ
ᴠᴐⱳᴒᴑᴢꞌᴒͼ꞉ꜜͼᴡⱳᴒͼᴡԜԝꞌᴒͼԝᴒꞌꜝᴤ᷅ͼ

Ⱬᴅ᷄᷉Ⱡ᷊᷇
ⱪꞌ꞉ꜜ꞉ᴐԜꞌͼᴁᴟ꞉Ԝꞌͼ͟ᴟꜝᴡꜝᴐꜝꞌⱡͼⱫᴅ᷄᷉Ⱡ᷊᷊᷇᷄᷇
ⱨꜛᴒꜜᴑꜛᴒꜜᴡͼ᷊᷅᷇ⱴ꞉ꜜԜꞌⱡͼ᷇ⱠͼꜗԜꜜᴢԜᴟᴦ᷉᷇᷈ⅎ
ⱪꜝꜜⱱ꞉ᴑᴒꜜᴡ꞉Ԝꞌ
͟ԜⱲᴒͼⅎ
ⱫᴦԜᴥͼⱪꜝᴟꜞ᷅
Treatment Period Dosing Schedule
Treatment Period
Treatment Arms: DX-2930 or Placebo
Dose Number
Dose Day/Week
300 mg
every 2 
weeks
300 mg
every 4 
weeks
150 mg
every 4 
weeks
Placebo
᷈
ⱫԜᴦͼ᷇᷆ᴄᴒᴒꞋͼ᷇
Ⱬᴅ᷄᷉Ⱡ᷊᷇
Ⱬᴅ᷄᷉Ⱡ᷊᷇
Ⱬᴅ᷄᷉Ⱡ᷊᷇
͟ꞌԜᴐᴒԝꜝ
᷉
ⱫԜᴦͼ᷈᷾᷆ᴄᴒᴒꞋͼ᷉
Ⱬᴅ᷄᷉Ⱡ᷊᷇
͟ꞌԜᴐᴒԝꜝ
͟ꞌԜᴐᴒԝꜝ
͟ꞌԜᴐᴒԝꜝ
᷊
ⱫԜᴦͼ᷉˲᷆ᴄᴒᴒꞋͼ᷾
Ⱬᴅ᷄᷉Ⱡ᷊᷇
Ⱬᴅ᷄᷉Ⱡ᷊᷇
Ⱬᴅ᷄᷉Ⱡ᷊᷇
͟ꞌԜᴐᴒԝꜝ
᷾
ⱫԜᴦͼ᷾᷉᷆ᴄᴒᴒꞋͼ⅍
Ⱬᴅ᷄᷉Ⱡ᷊᷇
͟ꞌԜᴐᴒԝꜝ
͟ꞌԜᴐᴒԝꜝ
͟ꞌԜᴐᴒԝꜝ
᷿
ⱫԜᴦͼ᷿⅍᷆ᴄᴒᴒꞋͼ˲
Ⱬᴅ᷄᷉Ⱡ᷊᷇
Ⱬᴅ᷄᷉Ⱡ᷊᷇
Ⱬᴅ᷄᷉Ⱡ᷊᷇
͟ꞌԜᴐᴒԝꜝ
⅍
ⱫԜᴦͼⅎ᷇᷆ᴄᴒᴒꞋͼ᷈᷇
Ⱬᴅ᷄᷉Ⱡ᷊᷇
͟ꞌԜᴐᴒԝꜝ
͟ꞌԜᴐᴒԝꜝ
͟ꞌԜᴐᴒԝꜝ
ⅎ
ⱫԜᴦͼ˲᷾᷆ᴄᴒᴒꞋͼ᷈᷉
Ⱬᴅ᷄᷉Ⱡ᷊᷇
Ⱬᴅ᷄᷉Ⱡ᷊᷇
Ⱬᴅ᷄᷉Ⱡ᷊᷇
͟ꞌԜᴐᴒԝꜝ
˲
ⱫԜᴦͼⱠ˲᷆ᴄᴒᴒꞋͼ᷈᷾
Ⱬᴅ᷄᷉Ⱡ᷊᷇
͟ꞌԜᴐᴒԝꜝ
͟ꞌԜᴐᴒԝꜝ
͟ꞌԜᴐᴒԝꜝ
Ⱡ
ⱫԜᴦͼ᷈᷈᷉᷆ᴄᴒᴒꞋͼ᷈⅍
Ⱬᴅ᷄᷉Ⱡ᷊᷇
Ⱬᴅ᷄᷉Ⱡ᷊᷇
Ⱬᴅ᷄᷉Ⱡ᷊᷇
͟ꞌԜᴐᴒԝꜝ
᷈᷇
ⱫԜᴦͼ᷈᷉⅍᷆ᴄᴒᴒꞋͼ᷈˲
Ⱬᴅ᷄᷉Ⱡ᷊᷇
͟ꞌԜᴐᴒԝꜝ
͟ꞌԜᴐᴒԝꜝ
͟ꞌԜᴐᴒԝꜝ
᷈᷈
ⱫԜᴦͼ᷈᷾᷇᷆ᴄᴒᴒꞋͼ᷉᷇
Ⱬᴅ᷄᷉Ⱡ᷊᷇
Ⱬᴅ᷄᷉Ⱡ᷊᷇
Ⱬᴅ᷄᷉Ⱡ᷊᷇
͟ꞌԜᴐᴒԝꜝ
᷈᷉
ⱫԜᴦͼ᷿᷈᷾᷆ᴄᴒᴒꞋͼ᷉᷉
Ⱬᴅ᷄᷉Ⱡ᷊᷇
͟ꞌԜᴐᴒԝꜝ
͟ꞌԜᴐᴒԝꜝ
͟ꞌԜᴐᴒԝꜝ
᷊᷈
ⱫԜᴦͼ᷈⅍˲᷆ᴄᴒᴒꞋͼ᷉᷾
Ⱬᴅ᷄᷉Ⱡ᷊᷇
Ⱬᴅ᷄᷉Ⱡ᷊᷇
Ⱬᴅ᷄᷉Ⱡ᷊᷇
͟ꞌԜᴐᴒԝꜝ
᷄᷄
ⱫԜᴦͼ᷈˲᷉᷆ᴄᴒᴒꞋͼ᷉⅍
꜠ꜝͼⱫꜝᴠᴒ
꜠ꜝͼⱫꜝᴠᴒ
꜠ꜝͼⱫꜝᴠᴒ
꜠ꜝͼⱫꜝᴠᴒ
꜡ꜞᴒꜜ᷄ꜙԜԝᴒꞌͼⱬᴥᴡᴒꜜᴠ꞉ꜝꜜͼӿ꜡ꜙⱬԐͼᴀᴡᴢᴑᴦⱡ
ᴀᴢԝ꞊ᴒᴐᴡᴠͼᴤⱳꜝͼᴐꜝꜛꜞꞌᴒᴡᴒͼᴡⱳᴒͼᴡᴟᴒԜᴡꜛᴒꜜᴡͼꜞᴒᴟ꞉ꜝᴑͼᴤ꞉ꞌꞌͼԝᴒͼꜝⱱⱱᴒᴟᴒᴑͼᴡⱳᴒͼꜝꜞᴡ꞉ꜝꜜͼꜝⱱͼᴒꜜᴟꜝꞌꞌ꞉ꜜⱲͼ꞉ꜜͼԜꜜͼ
ꜝꜞᴒꜜ᷄ꞌԜԝᴒꞌͼᴒᴥᴡᴒꜜᴠ꞉ꜝꜜͼӿ꜡ꜙⱬԐͼᴠᴡᴢᴑᴦͼᴡⱳԜᴡͼᴤ꞉ꞌꞌͼԝᴒͼᴑᴒᴠᴐᴟ꞉ԝᴒᴑͼ꞉ꜜͼԜͼᴠᴒꜞԜᴟԜᴡᴒͼꜞᴟꜝᴡꜝᴐꜝꞌͼӿⱫᴅ᷄᷉Ⱡ᷊᷇᷄᷇᷾Ԑ᷅ͼ
ⱴꜝꞌꞌꜝᴤ᷄ᴂꜞͼ͟ᴒᴟ꞉ꜝᴑⱡ
ᴀᴢԝ꞊ᴒᴐᴡᴠͼᴤⱳꜝͼᴑꜝͼꜜꜝᴡͼꜞԜᴟᴡ꞉ᴐ꞉ꜞԜᴡᴒͼ꞉ꜜͼᴡⱳᴒͼ꜡ꜙⱬͼᴤ꞉ꞌꞌͼᴢꜜᴑᴒᴟⱲꜝͼᴠԜⱱᴒᴡᴦͼԜꜜᴑͼԜᴑᴑ꞉ᴡ꞉ꜝꜜԜꞌͼᴒᴣԜꞌᴢԜᴡ꞉ꜝꜜᴠͼ
ӿ꞉᷅ᴒ᷅ԓͼ͟ꜘͼԜꜜᴑͼ͟ⱫԐͼᴑᴢᴟ꞉ꜜⱲͼԜꜜͼ˲ͼᴤᴒᴒꞋͼⱱꜝꞌꞌꜝᴤ᷄ᴢꜞͼꜞᴒᴟ꞉ꜝᴑ᷅ͼᴀᴢԝ꞊ᴒᴐᴡᴠͼӿꜝᴟͼᴐԜᴟᴒⱲ꞉ᴣᴒᴟᴠԐͼᴤ꞉ꞌꞌͼԝᴒͼ
꞉ꜜᴠᴡᴟᴢᴐᴡᴒᴑͼᴡꜝͼ꞉ꜜⱱꜝᴟꜛͼᴡⱳᴒͼᴠ꞉ᴡᴒͼꜝⱱͼԜꜜᴦͼⱶⱨⱬͼԜᴡᴡԜᴐꞋͼᴡⱳᴒᴦͼᴒᴥꜞᴒᴟ꞉ᴒꜜᴐᴒͼⱱꜝᴟͼᴢꜞͼᴡꜝͼ᷊᷇ͼᴑԜᴦᴠͼԜⱱᴡᴒᴟͼᴡⱳᴒͼ
ⱱ꞉ꜜԜꞌͼⱱꜝꞌꞌꜝᴤ᷄ᴢꜞͼᴣ꞉ᴠ꞉ᴡ᷅
Study Population:
ᴁⱳᴒͼᴠᴡᴢᴑᴦͼᴤ꞉ꞌꞌͼᴒꜜᴟꜝꞌꞌͼᴢꜞͼᴡꜝͼ᷈᷉᷇ͼᴠᴢԝ꞊ᴒᴐᴡᴠͼᴡꜝͼꜞᴟꜝᴣ꞉ᴑᴒͼ᷈᷇˲ͼᴐꜝꜛꜞꞌᴒᴡᴒᴑ᷅ͼᴀᴢԝ꞊ᴒᴐᴡᴠͼᴤ꞉ꞌꞌͼԝᴒͼ᷈᷉ᴦᴒԜᴟᴠͼ
ꜝⱱͼԜⱲᴒͼԜꜜᴑͼꜝꞌᴑᴒᴟͼᴤ꞉ᴡⱳͼԜͼᴐꜝꜜⱱ꞉ᴟꜛᴒᴑͼᴑ꞉ԜⱲꜜꜝᴠ꞉ᴠͼꜝⱱͼⱶⱨⱬͼӿᴁᴦꜞᴒͼⱷͼꜝᴟͼⱷⱷԐͼᴤⱳꜝͼᴒᴥꜞᴒᴟ꞉ᴒꜜᴐᴒͼԜᴡͼꞌᴒԜᴠᴡͼ᷈ͼ
ⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟ᷄ᴐꜝꜜⱱ꞉ᴟꜛᴒᴑͼԜᴡᴡԜᴐꞋͼꜞᴒᴟͼ᷾ͼᴤᴒᴒꞋᴠͼᴑᴢᴟ꞉ꜜⱲͼᴡⱳᴒͼᴟᴢꜜ᷄꞉ꜜͼꜞᴒᴟ꞉ꜝᴑ᷅ͼⱶⱨⱬͼᴑ꞉ԜⱲꜜꜝᴠ꞉ᴠͼᴤ꞉ꞌꞌͼԝᴒͼ
ᴐꜝꜜⱱ꞉ᴟꜛᴒᴑͼᴡⱳᴟꜝᴢⱲⱳͼᴑꜝᴐᴢꜛᴒꜜᴡᴒᴑͼᴐꞌ꞉ꜜ꞉ᴐԜꞌͼⱳ꞉ᴠᴡꜝᴟᴦͼᴐꜝꜜᴠ꞉ᴠᴡᴒꜜᴡͼᴤ꞉ᴡⱳͼⱶⱨⱬͼԜꜜᴑͼᴑ꞉ԜⱲꜜꜝᴠᴡ꞉ᴐͼᴡᴒᴠᴡ꞉ꜜⱲͼ
ᴐꜝꜜᴑᴢᴐᴡᴒᴑͼᴑᴢᴟ꞉ꜜⱲͼᴡⱳᴒͼᴠᴐᴟᴒᴒꜜ꞉ꜜⱲͼᴣ꞉ᴠ꞉ᴡ᷅ͼᴁⱳᴒͼᴠᴡᴢᴑᴦͼᴤ꞉ꞌꞌͼԜ꞉ꜛͼᴡꜝͼᴒꜜᴟꜝꞌꞌͼԜᴡͼꞌᴒԜᴠᴡͼ᷿ͼᴠᴢԝ꞊ᴒᴐᴡᴠͼᴤⱳꜝͼԜᴟᴒͼ
᷈᷉ͼᴡꜝͼ᷈ⅎͼᴦᴒԜᴟᴠͼꜝⱱͼԜⱲᴒ᷅
Criteria for Inclusion:
ᴀᴢԝ꞊ᴒᴐᴡᴠͼꜛᴢᴠᴡͼꜛᴒᴒᴡͼᴡⱳᴒͼⱱꜝꞌꞌꜝᴤ꞉ꜜⱲͼᴐᴟ꞉ᴡᴒᴟ꞉Ԝͼᴡꜝͼԝᴒͼᴒꜜᴟꜝꞌꞌᴒᴑͼ꞉ꜜͼᴡⱳ꞉ᴠͼᴠᴡᴢᴑᴦⱡ

Ⱬᴅ᷄᷉Ⱡ᷊᷇
ⱪꞌ꞉ꜜ꞉ᴐԜꞌͼᴁᴟ꞉Ԝꞌͼ͟ᴟꜝᴡꜝᴐꜝꞌⱡͼⱫᴅ᷄᷉Ⱡ᷊᷊᷇᷄᷇
ⱨꜛᴒꜜᴑꜛᴒꜜᴡͼ᷊᷅᷇ⱴ꞉ꜜԜꞌⱡͼ᷇ⱠͼꜗԜꜜᴢԜᴟᴦ᷉᷇᷈ⅎ
ⱪꜝꜜⱱ꞉ᴑᴒꜜᴡ꞉Ԝꞌ
͟ԜⱲᴒͼ˲
ⱫᴦԜᴥͼⱪꜝᴟꜞ᷅
᷈᷅ꜚԜꞌᴒᴠͼԜꜜᴑͼⱱᴒꜛԜꞌᴒᴠͼ᷈᷉ͼᴦᴒԜᴟᴠͼꜝⱱͼԜⱲᴒͼꜝᴟͼꜝꞌᴑᴒᴟͼԜᴡͼᴡⱳᴒͼᴡ꞉ꜛᴒͼꜝⱱͼᴠᴐᴟᴒᴒꜜ꞉ꜜⱲ᷅
᷉᷅Ⱬꜝᴐᴢꜛᴒꜜᴡᴒᴑͼᴑ꞉ԜⱲꜜꜝᴠ꞉ᴠͼꜝⱱͼⱶⱨⱬͼӿᴁᴦꜞᴒͼⱷͼꜝᴟͼⱷⱷԐͼԝԜᴠᴒᴑͼᴢꜞꜝꜜͼԜꞌꞌꜝⱱͼᴡⱳᴒͼⱱꜝꞌꞌꜝᴤ꞉ꜜⱲⱡͼ
᷄
Ⱬꜝᴐᴢꜛᴒꜜᴡᴒᴑͼᴐꞌ꞉ꜜ꞉ᴐԜꞌͼⱳ꞉ᴠᴡꜝᴟᴦͼᴐꜝꜜᴠ꞉ᴠᴡᴒꜜᴡͼᴤ꞉ᴡⱳͼⱶⱨⱬͼӿᴠᴢԝᴐᴢᴡԜꜜᴒꜝᴢᴠͼꜝᴟͼꜛᴢᴐꜝᴠԜꞌԓͼ
ꜜꜝꜜꜞᴟᴢᴟ꞉ᴡ꞉ᴐͼᴠᴤᴒꞌꞌ꞉ꜜⱲͼᴒꜞ꞉ᴠꜝᴑᴒᴠͼᴤ꞉ᴡⱳꜝᴢᴡͼԜᴐᴐꜝꜛꜞԜꜜᴦ꞉ꜜⱲͼᴢᴟᴡ꞉ᴐԜᴟ꞉ԜԐ᷅
᷄
Ⱬ꞉ԜⱲꜜꜝᴠᴡ꞉ᴐͼᴡᴒᴠᴡ꞉ꜜⱲͼᴟᴒᴠᴢꞌᴡᴠͼꜝԝᴡԜ꞉ꜜᴒᴑͼᴑᴢᴟ꞉ꜜⱲͼᴠᴐᴟᴒᴒꜜ꞉ꜜⱲͼᴡⱳԜᴡͼᴐꜝꜜⱱ꞉ᴟꜛͼⱶⱨⱬͼᴁᴦꜞᴒͼⱷͼꜝᴟͼⱷⱷⱡͼ
ⱪ᷈ͼ꞉ꜜⱳ꞉ԝ꞉ᴡꜝᴟͼӿⱪ᷈᷄ⱷ꜠ⱶԐͼⱱᴢꜜᴐᴡ꞉ꜝꜜԜꞌͼꞌᴒᴣᴒꞌͼⱣͼ᷾᷇ӼͼꜝⱱͼᴡⱳᴒͼꜜꜝᴟꜛԜꞌͼꞌᴒᴣᴒꞌ᷅ͼᴀᴢԝ꞊ᴒᴐᴡᴠͼᴤ꞉ᴡⱳͼ
ⱱᴢꜜᴐᴡ꞉ꜝꜜԜꞌͼⱪ᷈᷄ⱷ꜠ⱶͼꞌᴒᴣᴒꞌͼ᷿᷾᷇᷄᷇ӼͼꜝⱱͼᴡⱳᴒͼꜜꜝᴟꜛԜꞌͼꞌᴒᴣᴒꞌͼꜛԜᴦͼԝᴒͼᴒꜜᴟꜝꞌꞌᴒᴑͼ꞉ⱱͼᴡⱳᴒᴦͼԜꞌᴠꜝͼ
ⱳԜᴣᴒͼԜͼⱪ᷾ͼꞌᴒᴣᴒꞌͼԝᴒꞌꜝᴤͼᴡⱳᴒͼꜜꜝᴟꜛԜꞌͼᴟԜꜜⱲᴒ᷅ͼᴀᴢԝ꞊ᴒᴐᴡᴠͼꜛԜᴦͼԝᴒⱲ꞉ꜜͼꜞԜᴟᴡ꞉ᴐ꞉ꜞԜᴡ꞉ꜜⱲͼ꞉ꜜͼᴡⱳᴒͼᴟᴢꜜ᷄
꞉ꜜͼꜞᴒᴟ꞉ꜝᴑͼԝᴒⱱꜝᴟᴒͼᴡⱳᴒᴠᴒͼᴑ꞉ԜⱲꜜꜝᴠᴡ꞉ᴐͼᴟᴒᴠᴢꞌᴡᴠͼԜᴟᴒͼԜᴣԜ꞉ꞌԜԝꞌᴒ᷅ͼᴀᴢԝ꞊ᴒᴐᴡᴠͼꜛԜᴦͼԝᴒͼᴟᴒᴡᴒᴠᴡᴒᴑͼ꞉ⱱͼ
ᴟᴒᴠᴢꞌᴡᴠͼԜᴟᴒͼ꞉ꜜᴐꜝꜜⱲᴟᴢᴒꜜᴡͼᴤ꞉ᴡⱳͼᴐꞌ꞉ꜜ꞉ᴐԜꞌͼⱳ꞉ᴠᴡꜝᴟᴦͼꜝᴟͼԝᴒꞌ꞉ᴒᴣᴒᴑͼԝᴦͼᴡⱳᴒͼⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟͼᴡꜝͼԝᴒͼ
ᴐꜝꜜⱱꜝᴢꜜᴑᴒᴑͼԝᴦͼᴟᴒᴐᴒꜜᴡͼꜙᴁ͟ͼᴢᴠᴒ᷅
᷄
ⱨᴡͼꞌᴒԜᴠᴡͼꜝꜜᴒͼꜝⱱͼᴡⱳᴒͼⱱꜝꞌꞌꜝᴤ꞉ꜜⱲⱡͼⱨⱲᴒͼԜᴡͼᴟᴒꜞꜝᴟᴡᴒᴑͼꜝꜜᴠᴒᴡͼꜝⱱͼⱱ꞉ᴟᴠᴡͼԜꜜⱲ꞉ꜝᴒᴑᴒꜛԜͼᴠᴦꜛꜞᴡꜝꜛᴠͼ
ᶑ᷊᷇ͼᴦᴒԜᴟᴠԓͼԜͼⱱԜꜛ꞉ꞌᴦͼⱳ꞉ᴠᴡꜝᴟᴦͼᴐꜝꜜᴠ꞉ᴠᴡᴒꜜᴡͼᴤ꞉ᴡⱳͼⱶⱨⱬͼᴁᴦꜞᴒͼⱷͼꜝᴟͼⱷⱷԓͼꜝᴟͼⱪ᷈ꜟͼᴤ꞉ᴡⱳ꞉ꜜͼꜜꜝᴟꜛԜꞌͼ
ᴟԜꜜⱲᴒ᷅
᷊᷅ⱬᴥꜞᴒᴟ꞉ᴒꜜᴐ꞉ꜜⱲͼԜͼԝԜᴠᴒꞌ꞉ꜜᴒͼᴟԜᴡᴒͼꜝⱱͼԜᴡͼꞌᴒԜᴠᴡͼ᷈ͼⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟ᷄ᴐꜝꜜⱱ꞉ᴟꜛᴒᴑͼⱶⱨⱬͼԜᴡᴡԜᴐꞋͼꜞᴒᴟͼ᷾ᴤᴒᴒꞋᴠͼ
Ԝᴠͼᴐꜝꜜⱱ꞉ᴟꜛᴒᴑͼᴑᴢᴟ꞉ꜜⱲͼᴡⱳᴒͼᴟᴢꜜ᷄꞉ꜜͼꜞᴒᴟ꞉ꜝᴑ᷅ͼ
᷾᷅ⱨᴑᴢꞌᴡͼᴠᴢԝ꞊ᴒᴐᴡᴠͼԜꜜᴑͼᴐԜᴟᴒⱲ꞉ᴣᴒᴟᴠͼꜝⱱͼᴠᴢԝ꞊ᴒᴐᴡᴠͼᴢꜜᴑᴒᴟͼᴡⱳᴒͼԜⱲᴒͼꜝⱱͼ᷈˲ͼԜᴟᴒͼᴤ꞉ꞌꞌ꞉ꜜⱲͼԜꜜᴑͼԜԝꞌᴒͼᴡꜝͼᴟᴒԜᴑԓͼ
ᴢꜜᴑᴒᴟᴠᴡԜꜜᴑԓͼԜꜜᴑͼᴠ꞉ⱲꜜͼԜꜜͼ꞉ꜜⱱꜝᴟꜛᴒᴑͼᴐꜝꜜᴠᴒꜜᴡͼⱱꜝᴟꜛ᷅ͼᴀᴢԝ꞊ᴒᴐᴡᴠͼԜⱲᴒͼ᷈᷉ͼᴡꜝͼ᷈ⅎԓͼᴤⱳꜝᴠᴒͼᴐԜᴟᴒⱲ꞉ᴣᴒᴟͼ
ꜞᴟꜝᴣ꞉ᴑᴒᴠͼ꞉ꜜⱱꜝᴟꜛᴒᴑͼᴐꜝꜜᴠᴒꜜᴡԓͼԜꜜᴑͼԜᴟᴒͼᴤ꞉ꞌꞌ꞉ꜜⱲͼԜꜜᴑͼԜԝꞌᴒͼᴡꜝͼᴟᴒԜᴑԓͼᴢꜜᴑᴒᴟᴠᴡԜꜜᴑԓͼԜꜜᴑͼᴠ꞉ⱲꜜͼԜꜜͼ
Ԝᴠᴠᴒꜜᴡͼⱱꜝᴟꜛ᷅
᷿᷅ꜚԜꞌᴒᴠͼԜꜜᴑͼⱱᴒꜛԜꞌᴒᴠͼᴤⱳꜝͼԜᴟᴒͼⱱᴒᴟᴡ꞉ꞌᴒͼԜꜜᴑͼᴠᴒᴥᴢԜꞌꞌᴦͼԜᴐᴡ꞉ᴣᴒͼꜛᴢᴠᴡͼԜᴑⱳᴒᴟᴒͼᴡꜝͼᴐꜝꜜᴡᴟԜᴐᴒꜞᴡ꞉ꜝꜜͼ
ᴟᴒꜟᴢ꞉ᴟᴒꜛᴒꜜᴡᴠͼⱱꜝᴟͼᴡⱳᴒͼᴑᴢᴟԜᴡ꞉ꜝꜜͼꜝⱱͼᴡⱳᴒͼᴠᴡᴢᴑᴦͼԜᴠͼⱱꜝꞌꞌꜝᴤᴠⱡ
᷄
ⱴᴒꜛԜꞌᴒᴠͼꜝⱱͼᴐⱳ꞉ꞌᴑԝᴒԜᴟ꞉ꜜⱲͼꜞꜝᴡᴒꜜᴡ꞉ԜꞌͼꜛᴢᴠᴡͼԜⱲᴟᴒᴒͼᴡꜝͼԝᴒͼԜԝᴠᴡ꞉ꜜᴒꜜᴡͼꜝᴟͼ꞉ᴡͼ꞉ᴠͼᴟᴒᴐꜝꜛꜛᴒꜜᴑᴒᴑͼᴡꜝͼ
ᴢᴠᴒͼⱳ꞉Ⱳⱳꞌᴦͼᴒⱱⱱᴒᴐᴡ꞉ᴣᴒͼⱱꜝᴟꜛᴠͼꜝⱱͼᴐꜝꜜᴡᴟԜᴐᴒꜞᴡ꞉ꜝꜜͼⱱᴟꜝꜛͼᴠᴐᴟᴒᴒꜜ꞉ꜜⱲͼᴡⱳᴟꜝᴢⱲⱳͼ᷊᷇ᴑԜᴦᴠͼԜⱱᴡᴒᴟͼᴡⱳᴒͼ
ⱱ꞉ꜜԜꞌͼᴠᴡᴢᴑᴦͼᴣ꞉ᴠ꞉ᴡ᷅ͼᴁⱳ꞉ᴠͼ꞉ꜜᴐꞌᴢᴑᴒᴠͼꜞᴟꜝⱲᴒᴠᴡ꞉ꜜ᷄ꜝꜜꞌᴦͼꜝᴟԜꞌͼᴐꜝꜜᴡᴟԜᴐᴒꜞᴡ꞉ᴣᴒͼԜᴠᴠꜝᴐ꞉Ԝᴡᴒᴑͼᴤ꞉ᴡⱳͼ
꞉ꜜⱳ꞉ԝ꞉ᴡ꞉ꜝꜜͼꜝⱱͼꜝᴣᴢꞌԜᴡ꞉ꜝꜜͼӿꜝᴟԜꞌԓͼ꞉ꜜ꞊ᴒᴐᴡԜԝꞌᴒԓͼꜝᴟͼ꞉ꜛꜞꞌԜꜜᴡԜԝꞌᴒԐԓͼ꞉ꜜᴡᴟԜ᷄ᴢᴡᴒᴟ꞉ꜜᴒͼᴑᴒᴣ꞉ᴐᴒͼӿⱷᴂⱫԓͼԜꞌꞌͼ
ᴡᴦꜞᴒᴠԐԓͼꜝᴟͼ꞉ꜜᴡᴟԜᴢᴡᴒᴟ꞉ꜜᴒͼⱳꜝᴟꜛꜝꜜᴒͼᴟᴒꞌᴒԜᴠ꞉ꜜⱲͼᴠᴦᴠᴡᴒꜛᴠͼӿⱷᴂᴀԐ᷅ͼ꜠ꜝᴡᴒᴠⱡͼ᷈ԐͼⱨͼⱱᴒꜛԜꞌᴒͼᴤⱳꜝᴠᴒͼ
ꜛԜꞌᴒͼꜞԜᴟᴡꜜᴒᴟͼⱳԜᴠͼⱳԜᴑͼԜͼᴣԜᴠᴒᴐᴡꜝꜛᴦͼꜛᴢᴠᴡͼԜⱲᴟᴒᴒͼᴡꜝͼᴢᴠᴒͼꜝꜜᴒͼԜᴑᴑ꞉ᴡ꞉ꜝꜜԜꞌͼⱱꜝᴟꜛͼꜝⱱͼꜛᴒᴑ꞉ᴐԜꞌꞌᴦͼ
ԜᴐᴐᴒꜞᴡԜԝꞌᴒͼᴐꜝꜜᴡᴟԜᴐᴒꜞᴡ꞉ꜝꜜ᷅ͼ᷉ԐͼᴂᴠᴒͼꜝⱱͼԜͼꜛԜꞌᴒͼᴐꜝꜜᴑꜝꜛͼᴤ꞉ᴡⱳͼꜝᴟͼᴤ꞉ᴡⱳꜝᴢᴡͼᴠꜞᴒᴟꜛ꞉ᴐ꞉ᴑᴒͼꜝᴟͼ
ᴐᴒᴟᴣ꞉ᴐԜꞌͼᴐԜꜞԓͼᴑ꞉ԜꜞⱳᴟԜⱲꜛͼꜝᴟͼᴠꜞꜝꜜⱲᴒͼᴤ꞉ᴡⱳͼᴠꜞᴒᴟꜛ꞉ᴐ꞉ᴑᴒͼꜝᴟͼԜͼᴐꜝꜛԝ꞉ꜜԜᴡ꞉ꜝꜜͼӿᴑꜝᴢԝꞌᴒ᷄ԝԜᴟᴟ꞉ᴒᴟͼ
ꜛᴒᴡⱳꜝᴑᴠԐͼ꞉ᴠͼꜜꜝᴡͼᴐꜝꜜᴠ꞉ᴑᴒᴟᴒᴑͼⱳ꞉Ⱳⱳꞌᴦͼᴒⱱⱱᴒᴐᴡ꞉ᴣᴒ᷅ͼ
᷄
ⱴᴒꜛԜꞌᴒᴠͼꜝⱱͼꜜꜝꜜ᷄ᴐⱳ꞉ꞌᴑԝᴒԜᴟ꞉ꜜⱲͼꜞꜝᴡᴒꜜᴡ꞉Ԝꞌԓͼᴑᴒⱱ꞉ꜜᴒᴑͼԜᴠͼᴠᴢᴟⱲ꞉ᴐԜꞌꞌᴦͼᴠᴡᴒᴟ꞉ꞌᴒͼӿᴠᴡԜᴡᴢᴠͼꜞꜝᴠᴡͼ
ⱳᴦᴠᴡᴒᴟᴒᴐᴡꜝꜛᴦԓͼԝ꞉ꞌԜᴡᴒᴟԜꞌͼꜝꜝꜞⱳꜝᴟᴒᴐᴡꜝꜛᴦԓͼꜝᴟͼԝ꞉ꞌԜᴡᴒᴟԜꞌͼᴡᴢԝԜꞌͼꞌ꞉ⱲԜᴡ꞉ꜝꜜԐͼꜝᴟͼꜞꜝᴠᴡ᷄ꜛᴒꜜꜝꜞԜᴢᴠԜꞌͼ
ⱱꜝᴟͼԜᴡͼꞌᴒԜᴠᴡͼ᷈᷉ͼꜛꜝꜜᴡⱳᴠԓͼᴑꜝͼꜜꜝᴡͼᴟᴒꜟᴢ꞉ᴟᴒͼᴐꜝꜜᴡᴟԜᴐᴒꜞᴡ꞉ꜝꜜͼᴑᴢᴟ꞉ꜜⱲͼᴡⱳᴒͼᴠᴡᴢᴑᴦ᷅
᷄
ꜚԜꞌᴒᴠԓͼ꞉ꜜᴐꞌᴢᴑ꞉ꜜⱲͼꜛԜꞌᴒᴠͼᴤⱳꜝͼԜᴟᴒͼᴠᴢᴟⱲ꞉ᴐԜꞌꞌᴦͼᴠᴡᴒᴟ꞉ꞌᴒͼӿꜞꜝᴠᴡͼᴣԜᴠᴒᴐᴡꜝꜛᴦԐԓͼᴤ꞉ᴡⱳͼⱱᴒꜛԜꞌᴒͼ
ꜞԜᴟᴡꜜᴒᴟᴠͼꜝⱱͼᴐⱳ꞉ꞌᴑԝᴒԜᴟ꞉ꜜⱲͼꜞꜝᴡᴒꜜᴡ꞉ԜꞌͼꜛᴢᴠᴡͼԜⱲᴟᴒᴒͼᴡꜝͼԝᴒͼԜԝᴠᴡ꞉ꜜᴒꜜᴡͼꜝᴟͼᴒꞌᴠᴒͼᴢᴠᴒͼԜͼꜛᴒᴑ꞉ᴐԜꞌꞌᴦͼ
ԜᴐᴐᴒꜞᴡԜԝꞌᴒͼⱱꜝᴟꜛͼꜝⱱͼᴐꜝꜜᴡᴟԜᴐᴒꜞᴡ꞉ꜝꜜͼⱱᴟꜝꜛͼᴠᴐᴟᴒᴒꜜ꞉ꜜⱲͼᴡⱳᴟꜝᴢⱲⱳͼ⅍᷇ᴑԜᴦᴠͼԜⱱᴡᴒᴟͼᴡⱳᴒͼⱱ꞉ꜜԜꞌͼᴠᴡᴢᴑᴦͼ
ᴣ꞉ᴠ꞉ᴡ᷅ͼ
Criteria for Exclusion:
ᴀᴢԝ꞊ᴒᴐᴡᴠͼᴤⱳꜝͼꜛᴒᴒᴡͼԜꜜᴦͼꜝⱱͼᴡⱳᴒͼⱱꜝꞌꞌꜝᴤ꞉ꜜⱲͼᴐᴟ꞉ᴡᴒᴟ꞉Ԝͼᴤ꞉ꞌꞌͼԝᴒͼᴒᴥᴐꞌᴢᴑᴒᴑͼⱱᴟꜝꜛͼᴡⱳᴒͼᴠᴡᴢᴑᴦⱡ
᷈᷅ⱪꜝꜜᴐꜝꜛ꞉ᴡԜꜜᴡͼᴑ꞉ԜⱲꜜꜝᴠ꞉ᴠͼꜝⱱͼԜꜜꜝᴡⱳᴒᴟͼⱱꜝᴟꜛͼꜝⱱͼᴐⱳᴟꜝꜜ꞉ᴐԓͼᴟᴒᴐᴢᴟᴟᴒꜜᴡͼԜꜜⱲ꞉ꜝᴒᴑᴒꜛԜԓͼᴠᴢᴐⱳͼԜᴠͼ
Ԝᴐꜟᴢ꞉ᴟᴒᴑͼԜꜜⱲ꞉ꜝᴒᴑᴒꜛԜͼӿⱨⱨⱬԐԓͼⱶⱨⱬͼᴤ꞉ᴡⱳͼꜜꜝᴟꜛԜꞌͼⱪ᷈᷄ⱷ꜠ⱶͼӿԜꞌᴠꜝͼꞋꜜꜝᴤꜜͼԜᴠͼⱶⱨⱬͼᴁᴦꜞᴒͼⱷⱷⱷԐԓͼ

Ⱬᴅ᷄᷉Ⱡ᷊᷇
ⱪꞌ꞉ꜜ꞉ᴐԜꞌͼᴁᴟ꞉Ԝꞌͼ͟ᴟꜝᴡꜝᴐꜝꞌⱡͼⱫᴅ᷄᷉Ⱡ᷊᷊᷇᷄᷇
ⱨꜛᴒꜜᴑꜛᴒꜜᴡͼ᷊᷅᷇ⱴ꞉ꜜԜꞌⱡͼ᷇ⱠͼꜗԜꜜᴢԜᴟᴦ᷉᷇᷈ⅎ
ⱪꜝꜜⱱ꞉ᴑᴒꜜᴡ꞉Ԝꞌ
͟ԜⱲᴒͼⱠ
ⱫᴦԜᴥͼⱪꜝᴟꜞ᷅
꞉ᴑ꞉ꜝꜞԜᴡⱳ꞉ᴐͼԜꜜⱲ꞉ꜝᴒᴑᴒꜛԜԓͼꜝᴟͼᴟᴒᴐᴢᴟᴟᴒꜜᴡͼԜꜜⱲ꞉ꜝᴒᴑᴒꜛԜͼԜᴠᴠꜝᴐ꞉Ԝᴡᴒᴑͼᴤ꞉ᴡⱳͼᴢᴟᴡ꞉ᴐԜᴟ꞉Ԝ᷅
᷉᷅͟Ԝᴟᴡ꞉ᴐ꞉ꜞԜᴡ꞉ꜝꜜͼ꞉ꜜͼԜͼꜞᴟ꞉ꜝᴟͼⱫᴅ᷄᷉Ⱡ᷊᷇ͼᴠᴡᴢᴑᴦ᷅
᷊᷅Ⱬꜝᴠ꞉ꜜⱲͼᴤ꞉ᴡⱳͼԜꜜͼ꞉ꜜᴣᴒᴠᴡ꞉ⱲԜᴡ꞉ꜝꜜԜꞌͼᴑᴟᴢⱲͼꜝᴟͼᴒᴥꜞꜝᴠᴢᴟᴒͼᴡꜝͼԜꜜͼ꞉ꜜᴣᴒᴠᴡ꞉ⱲԜᴡ꞉ꜝꜜԜꞌͼᴑᴒᴣ꞉ᴐᴒͼᴤ꞉ᴡⱳ꞉ꜜͼ
᷾ᴤᴒᴒꞋᴠͼꜞᴟ꞉ꜝᴟͼᴡꜝͼᴠᴐᴟᴒᴒꜜ꞉ꜜⱲ᷅
᷾᷅ⱬᴥꜞꜝᴠᴢᴟᴒͼᴡꜝͼԜꜜⱲ꞉ꜝᴡᴒꜜᴠ꞉ꜜ᷄ᴐꜝꜜᴣᴒᴟᴡ꞉ꜜⱲͼᴒꜜᴧᴦꜛᴒͼӿⱨⱪⱬԐͼ꞉ꜜⱳ꞉ԝ꞉ᴡꜝᴟᴠͼꜝᴟͼԜꜜᴦͼᴒᴠᴡᴟꜝⱲᴒꜜ᷄ᴐꜝꜜᴡԜ꞉ꜜ꞉ꜜⱲͼ
ꜛᴒᴑ꞉ᴐԜᴡ꞉ꜝꜜᴠͼᴤ꞉ᴡⱳͼᴠᴦᴠᴡᴒꜛ꞉ᴐͼԜԝᴠꜝᴟꜞᴡ꞉ꜝꜜͼӿᴠᴢᴐⱳͼԜᴠͼꜝᴟԜꞌͼᴐꜝꜜᴡᴟԜᴐᴒꜞᴡ꞉ᴣᴒᴠͼꜝᴟͼⱳꜝᴟꜛꜝꜜԜꞌͼ
ᴟᴒꜞꞌԜᴐᴒꜛᴒꜜᴡͼᴡⱳᴒᴟԜꜞᴦԐͼᴤ꞉ᴡⱳ꞉ꜜͼ᷾ͼᴤᴒᴒꞋᴠͼꜞᴟ꞉ꜝᴟͼᴡꜝͼᴠᴐᴟᴒᴒꜜ꞉ꜜⱲ᷅
᷿᷅ⱬᴥꜞꜝᴠᴢᴟᴒͼᴡꜝͼԜꜜᴑᴟꜝⱲᴒꜜᴠͼӿᴒ᷅Ⱳ᷅ͼᴠᴡԜꜜꜝᴧꜝꞌꜝꞌԓͼᴑԜꜜԜᴧꜝꞌԓͼꜝᴥԜꜜᴑᴟꜝꞌꜝꜜᴒԓͼꜛᴒᴡⱳᴦꞌᴡᴒᴠᴡꜝᴠᴡᴒᴟꜝꜜᴒԓͼ
ᴡᴒᴠᴡꜝᴠᴡᴒᴟꜝꜜᴒԐͼᴤ꞉ᴡⱳ꞉ꜜͼ᷉ͼᴤᴒᴒꞋᴠͼꜞᴟ꞉ꜝᴟͼᴡꜝͼᴒꜜᴡᴒᴟ꞉ꜜⱲͼᴡⱳᴒͼᴟᴢꜜ᷄꞉ꜜͼꜞᴒᴟ꞉ꜝᴑ᷅ͼ
⅍᷅ᴂᴠᴒͼꜝⱱͼꞌꜝꜜⱲ᷄ᴡᴒᴟꜛͼꜞᴟꜝꜞⱳᴦꞌԜᴐᴡ꞉ᴐͼᴡⱳᴒᴟԜꜞᴦͼⱱꜝᴟͼⱶⱨⱬͼӿⱪ᷈᷄ⱷ꜠ⱶԓͼԜᴡᴡᴒꜜᴢԜᴡᴒᴑͼԜꜜᴑᴟꜝⱲᴒꜜᴠԓͼꜝᴟͼ
Ԝꜜᴡ꞉᷄ⱱ꞉ԝᴟ꞉ꜜꜝꞌᴦᴡ꞉ᴐᴠԐͼᴤ꞉ᴡⱳ꞉ꜜͼ᷉ͼᴤᴒᴒꞋᴠͼꜞᴟ꞉ꜝᴟͼᴡꜝͼᴒꜜᴡᴒᴟ꞉ꜜⱲͼᴡⱳᴒͼᴟᴢꜜ᷄꞉ꜜͼꜞᴒᴟ꞉ꜝᴑ᷅
ⅎ᷅ᴂᴠᴒͼꜝⱱͼᴠⱳꜝᴟᴡ᷄ᴡᴒᴟꜛͼꜞᴟꜝꜞⱳᴦꞌԜᴥ꞉ᴠͼⱱꜝᴟͼⱶⱨⱬͼᴤ꞉ᴡⱳ꞉ꜜͼⅎͼᴑԜᴦᴠͼꜞᴟ꞉ꜝᴟͼᴡꜝͼᴒꜜᴡᴒᴟ꞉ꜜⱲͼᴡⱳᴒͼᴟᴢꜜ᷄꞉ꜜͼꜞᴒᴟ꞉ꜝᴑ᷅ͼ
ᴀⱳꜝᴟᴡ᷄ᴡᴒᴟꜛͼꜞᴟꜝꜞⱳᴦꞌԜᴥ꞉ᴠͼ꞉ᴠͼᴑᴒⱱ꞉ꜜᴒᴑͼԜᴠͼⱪ᷈᷄ⱷ꜠ⱶԓͼԜᴡᴡᴒꜜᴢԜᴡᴒᴑͼԜꜜᴑᴟꜝⱲᴒꜜᴠԓͼꜝᴟͼԜꜜᴡ꞉᷄ⱱ꞉ԝᴟ꞉ꜜꜝꞌᴦᴡ꞉ᴐᴠͼ
ᴢᴠᴒᴑͼᴡꜝͼԜᴣꜝ꞉ᴑͼԜꜜⱲ꞉ꜝᴒᴑᴒꜛԜͼᴐꜝꜛꜞꞌ꞉ᴐԜᴡ꞉ꜝꜜᴠͼⱱᴟꜝꜛͼꜛᴒᴑ꞉ᴐԜꞌꞌᴦͼ꞉ꜜᴑ꞉ᴐԜᴡᴒᴑͼꜞᴟꜝᴐᴒᴑᴢᴟᴒᴠ᷅
˲᷅ⱨꜜᴦͼꜝⱱͼᴡⱳᴒͼⱱꜝꞌꞌꜝᴤ꞉ꜜⱲͼꞌ꞉ᴣᴒᴟͼⱱᴢꜜᴐᴡ꞉ꜝꜜͼᴡᴒᴠᴡͼԜԝꜜꜝᴟꜛԜꞌ꞉ᴡ꞉ᴒᴠⱡͼԜꞌԜꜜ꞉ꜜᴒͼԜꜛ꞉ꜜꜝᴡᴟԜꜜᴠⱱᴒᴟԜᴠᴒͼӿⱨꜙᴁԐͼ
ⱥ᷊ᴥͼᴢꜞꜞᴒᴟͼꞌ꞉ꜛ꞉ᴡͼꜝⱱͼꜜꜝᴟꜛԜꞌԓͼꜝᴟͼԜᴠꜞԜᴟᴡԜᴡᴒͼԜꜛ꞉ꜜꜝᴡᴟԜꜜᴠⱱᴒᴟԜᴠᴒͼӿⱨᴀᴁԐͼⱥͼ᷊ᴥͼᴢꜞꜞᴒᴟͼꞌ꞉ꜛ꞉ᴡͼꜝⱱͼ
ꜜꜝᴟꜛԜꞌԓͼꜝᴟͼᴡꜝᴡԜꞌͼԝ꞉ꞌ꞉ᴟᴢԝ꞉ꜜͼⱥͼ᷉ᴥͼᴢꜞꜞᴒᴟͼꞌ꞉ꜛ꞉ᴡͼꜝⱱͼꜜꜝᴟꜛԜꞌͼӿᴢꜜꞌᴒᴠᴠͼᴡⱳᴒͼԝ꞉ꞌ꞉ᴟᴢԝ꞉ꜜͼᴒꞌᴒᴣԜᴡ꞉ꜝꜜͼ꞉ᴠͼԜͼ
ᴟᴒᴠᴢꞌᴡͼꜝⱱͼⱵ꞉ꞌԝᴒᴟᴡᶳᴠͼᴠᴦꜜᴑᴟꜝꜛᴒԐ᷅
Ⱡ᷅͟ᴟᴒⱲꜜԜꜜᴐᴦͼꜝᴟͼԝᴟᴒԜᴠᴡⱱᴒᴒᴑ꞉ꜜⱲ᷅
᷈᷇᷅ᴀᴢԝ꞊ᴒᴐᴡͼⱳԜᴠͼԜꜜᴦͼᴐꜝꜜᴑ꞉ᴡ꞉ꜝꜜͼᴡⱳԜᴡԓͼ꞉ꜜͼᴡⱳᴒͼꜝꜞ꞉ꜜ꞉ꜝꜜͼꜝⱱͼᴡⱳᴒͼⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟͼꜝᴟͼᴀꜞꜝꜜᴠꜝᴟԓͼꜛԜᴦͼ
ᴐꜝꜛꜞᴟꜝꜛ꞉ᴠᴒͼᴡⱳᴒ꞉ᴟͼᴠԜⱱᴒᴡᴦͼꜝᴟͼᴐꜝꜛꜞꞌ꞉Ԝꜜᴐᴒԓͼꜞᴟᴒᴐꞌᴢᴑᴒͼᴠᴢᴐᴐᴒᴠᴠⱱᴢꞌͼᴐꜝꜜᴑᴢᴐᴡͼꜝⱱͼᴡⱳᴒͼᴠᴡᴢᴑᴦԓͼꜝᴟͼ
꞉ꜜᴡᴒᴟⱱᴒᴟᴒͼᴤ꞉ᴡⱳͼ꞉ꜜᴡᴒᴟꜞᴟᴒᴡԜᴡ꞉ꜝꜜͼꜝⱱͼᴡⱳᴒͼᴟᴒᴠᴢꞌᴡᴠͼӿᴒ᷅Ⱳ᷅ԓͼⱳ꞉ᴠᴡꜝᴟᴦͼꜝⱱͼᴠᴢԝᴠᴡԜꜜᴐᴒͼԜԝᴢᴠᴒͼꜝᴟͼᴑᴒꜞᴒꜜᴑᴒꜜᴐᴒԓͼ
ᴠ꞉Ⱳꜜ꞉ⱱ꞉ᴐԜꜜᴡͼꜞᴟᴒ᷄ᴒᴥ꞉ᴠᴡ꞉ꜜⱲͼ꞉ꞌꞌꜜᴒᴠᴠͼꜝᴟͼꜝᴡⱳᴒᴟͼꜛԜ꞊ꜝᴟͼᴐꜝꜛꜝᴟԝ꞉ᴑ꞉ᴡᴦͼᴡⱳԜᴡͼᴡⱳᴒͼⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟͼᴐꜝꜜᴠ꞉ᴑᴒᴟᴠͼ
ꜛԜᴦͼᴐꜝꜜⱱꜝᴢꜜᴑͼᴡⱳᴒͼ꞉ꜜᴡᴒᴟꜞᴟᴒᴡԜᴡ꞉ꜝꜜͼꜝⱱͼᴠᴡᴢᴑᴦͼᴟᴒᴠᴢꞌᴡᴠԐ᷅
Test Product; Dose; and Mode of Administration:
Ⱬᴅ᷄᷉Ⱡ᷊᷇ͼ꞉ᴠͼԜͼᴠᴡᴒᴟ꞉ꞌᴒԓͼꜞᴟᴒᴠᴒᴟᴣԜᴡ꞉ᴣᴒ᷄ⱱᴟᴒᴒͼᴠꜝꞌᴢᴡ꞉ꜝꜜͼⱱꜝᴟͼ꞉ꜜ꞊ᴒᴐᴡ꞉ꜝꜜԓͼꜞⱶͼ⅍᷅᷇᷅ͼᴁⱳᴒͼԜᴐᴡ꞉ᴣᴒͼ꞉ꜜⱲᴟᴒᴑ꞉ᴒꜜᴡԓͼ
Ⱬᴅ᷄᷉Ⱡ᷊᷇ԓͼ꞉ᴠͼⱱꜝᴟꜛᴢꞌԜᴡᴒᴑͼᴢᴠ꞉ꜜⱲͼᴡⱳᴒͼⱱꜝꞌꞌꜝᴤ꞉ꜜⱲͼᴐꜝꜛꜞᴒꜜᴑ꞉Ԝꞌͼᴐꜝꜛꜞꜝꜜᴒꜜᴡᴠⱡͼ᷊᷇ͼꜛꜚͼᴠꜝᴑ꞉ᴢꜛͼ
ꜞⱳꜝᴠꜞⱳԜᴡᴒͼᴑ꞉ԝԜᴠ꞉ᴐͼᴑ꞉ⱳᴦᴑᴟԜᴡᴒԓͼ᷈Ⱡ᷅⅍ͼꜛꜚͼᴐ꞉ᴡᴟ꞉ᴐͼԜᴐ꞉ᴑԓͼ᷿᷇ͼꜛꜚͼⱳ꞉ᴠᴡ꞉ᴑ꞉ꜜᴒԓͼⱠ᷇ꜛꜚͼᴠꜝᴑ꞉ᴢꜛͼᴐⱳꞌꜝᴟ꞉ᴑᴒԓͼ
᷇᷅᷇᷈Ӽͼ͟ꜝꞌᴦᴠꜝᴟԝԜᴡᴒͼ˲᷇᷅ͼⱬԜᴐⱳͼᴣ꞉ԜꞌͼᴐꜝꜜᴡԜ꞉ꜜᴠͼԜͼꜜꜝꜛ꞉ꜜԜꞌͼᴐꜝꜜᴐᴒꜜᴡᴟԜᴡ꞉ꜝꜜͼꜝⱱͼ᷿᷈᷇ͼꜛⱲͼⱫᴅ᷄᷉Ⱡ᷊᷇ͼ
Ԝᴐᴡ꞉ᴣᴒͼ꞉ꜜⱲᴟᴒᴑ꞉ᴒꜜᴡͼ꞉ꜜͼ᷈ꜛꜙͼᴠꜝꞌᴢᴡ꞉ꜝꜜ᷅ͼᴁⱳᴒͼᴡᴒᴠᴡͼꜞᴟꜝᴑᴢᴐᴡͼᴤ꞉ꞌꞌͼԝᴒͼԜᴑꜛ꞉ꜜ꞉ᴠᴡᴒᴟᴒᴑͼᴠᴢԝᴐᴢᴡԜꜜᴒꜝᴢᴠꞌᴦͼ꞉ꜜᴡꜝͼ
ᴡⱳᴒͼᴢꜞꜞᴒᴟͼԜᴟꜛͼ꞉ꜜͼԜͼԝꞌ꞉ꜜᴑᴒᴑͼꜛԜꜜꜜᴒᴟ᷅
ⱴꜝᴟͼᴒԜᴐⱳͼ᷊᷇᷇ꜛⱲͼᴑꜝᴠᴒͼꜝⱱͼⱫᴅ᷄᷉Ⱡ᷊᷇ԓͼᴒԜᴐⱳͼᴠᴢԝ꞊ᴒᴐᴡͼᴤ꞉ꞌꞌͼᴟᴒᴐᴒ꞉ᴣᴒͼԜͼᴡꜝᴡԜꞌͼꜝⱱͼ᷉ͼꜛꜙԓͼᴑ꞉ᴣ꞉ᴑᴒᴑͼ꞉ꜜᴡꜝͼ
᷉ᴠᴒꜞԜᴟԜᴡᴒͼ᷈᷅᷇ͼꜛꜙͼᴀⱪͼ꞉ꜜ꞊ᴒᴐᴡ꞉ꜝꜜᴠͼꜝⱱͼⱫᴅ᷄᷉Ⱡ᷊᷇᷅ͼᴁⱳᴒͼ᷉ͼ꞉ꜜ꞊ᴒᴐᴡ꞉ꜝꜜᴠͼᴤ꞉ꞌꞌͼԝᴒͼⱲ꞉ᴣᴒꜜͼ꞉ꜜͼᴡⱳᴒͼᴠԜꜛᴒͼ
ᴢꜞꜞᴒᴟͼԜᴟꜛԓͼᴤ꞉ᴡⱳͼԜᴡͼꞌᴒԜᴠᴡͼ᷉ͼᴐꜛͼᴠᴒꜞԜᴟԜᴡ꞉ꜝꜜͼԝᴒᴡᴤᴒᴒꜜͼᴒԜᴐⱳͼ꞉ꜜ꞊ᴒᴐᴡ꞉ꜝꜜͼᴠ꞉ᴡᴒ᷅
ⱴꜝᴟͼᴒԜᴐⱳͼ᷿᷈᷇ͼꜛⱲͼᴑꜝᴠᴒͼꜝⱱͼⱫᴅ᷄᷉Ⱡ᷊᷇ԓͼᴒԜᴐⱳͼᴠᴢԝ꞊ᴒᴐᴡͼᴤ꞉ꞌꞌͼᴟᴒᴐᴒ꞉ᴣᴒͼԜͼᴡꜝᴡԜꞌͼꜝⱱͼ᷉ͼꜛꜙԓͼᴑ꞉ᴣ꞉ᴑᴒᴑͼ꞉ꜜᴡꜝͼ
᷉ᴠᴒꜞԜᴟԜᴡᴒͼ᷈᷅᷇ͼꜛꜙͼᴀⱪͼ꞉ꜜ꞊ᴒᴐᴡ꞉ꜝꜜᴠԓͼᴤⱳᴒᴟᴒͼꜝꜜᴒͼ꞉ꜜ꞊ᴒᴐᴡ꞉ꜝꜜͼ꞉ᴠͼⱫᴅ᷄᷉Ⱡ᷊᷇ͼԜꜜᴑͼᴡⱳᴒͼꜝᴡⱳᴒᴟͼ꞉ᴠͼꜞꞌԜᴐᴒԝꜝ᷅ͼ
ᴁⱳᴒͼ᷉ͼ꞉ꜜ꞊ᴒᴐᴡ꞉ꜝꜜᴠͼᴤ꞉ꞌꞌͼԝᴒͼⱲ꞉ᴣᴒꜜͼ꞉ꜜͼᴡⱳᴒͼᴠԜꜛᴒͼᴢꜞꜞᴒᴟͼԜᴟꜛԓͼᴤ꞉ᴡⱳͼԜᴡͼꞌᴒԜᴠᴡͼ᷉ͼᴐꜛͼᴠᴒꜞԜᴟԜᴡ꞉ꜝꜜͼԝᴒᴡᴤᴒᴒꜜͼ
ᴒԜᴐⱳͼ꞉ꜜ꞊ᴒᴐᴡ꞉ꜝꜜͼᴠ꞉ᴡᴒ᷅
Placebo; Dose; and Mode of Administration:
͟ꞌԜᴐᴒԝꜝͼᴐꜝꜜᴠ꞉ᴠᴡᴠͼꜝⱱͼᴡⱳᴒͼ꞉ꜜԜᴐᴡ꞉ᴣᴒͼⱱꜝᴟꜛᴢꞌԜᴡ꞉ꜝꜜͼꜝⱱͼᴡⱳᴒͼᴡᴒᴠᴡͼꜞᴟꜝᴑᴢᴐᴡⱡͼ᷊᷇ͼꜛꜚͼᴠꜝᴑ꞉ᴢꜛͼꜞⱳꜝᴠꜞⱳԜᴡᴒͼ
ᴑ꞉ԝԜᴠ꞉ᴐͼᴑ꞉ⱳᴦᴑᴟԜᴡᴒԓͼ᷈Ⱡ᷅⅍ꜛꜚͼᴐ꞉ᴡᴟ꞉ᴐͼԜᴐ꞉ᴑԓͼ᷿᷇ͼꜛꜚͼⱳ꞉ᴠᴡ꞉ᴑ꞉ꜜᴒԓͼⱠ᷇ͼꜛꜚͼᴠꜝᴑ꞉ᴢꜛͼᴐⱳꞌꜝᴟ꞉ᴑᴒԓͼꜞⱶͼ⅍᷅᷇ͼ

Ⱬᴅ᷄᷉Ⱡ᷊᷇
ⱪꞌ꞉ꜜ꞉ᴐԜꞌͼᴁᴟ꞉Ԝꞌͼ͟ᴟꜝᴡꜝᴐꜝꞌⱡͼⱫᴅ᷄᷉Ⱡ᷊᷊᷇᷄᷇
ⱨꜛᴒꜜᴑꜛᴒꜜᴡͼ᷊᷅᷇ⱴ꞉ꜜԜꞌⱡͼ᷇ⱠͼꜗԜꜜᴢԜᴟᴦ᷉᷇᷈ⅎ
ⱪꜝꜜⱱ꞉ᴑᴒꜜᴡ꞉Ԝꞌ
͟ԜⱲᴒͼ᷈᷇
ⱫᴦԜᴥͼⱪꜝᴟꜞ᷅
ᴤ꞉ᴡⱳͼ᷇᷅᷇᷈Ӽͼ͟ꜝꞌᴦᴠꜝᴟԝԜᴡᴒ˲᷇᷅ͼ
͟ꞌԜᴐᴒԝꜝͼᴑꜝᴠᴒᴠͼᴤ꞉ꞌꞌͼԝᴒͼԜᴑꜛ꞉ꜜ꞉ᴠᴡᴒᴟᴒᴑͼᴡꜝͼᴠᴢԝ꞊ᴒᴐᴡᴠͼᴟԜꜜᴑꜝꜛ꞉ᴧᴒᴑͼᴡꜝͼᴡⱳᴒͼꜞꞌԜᴐᴒԝꜝͼᴡᴟᴒԜᴡꜛᴒꜜᴡͼԜᴟꜛͼԜꜜᴑͼ
꞉ꜜͼԝᴒᴡᴤᴒᴒꜜͼᴑꜝᴠᴒᴠͼꜝⱱͼⱫᴅ᷄᷉Ⱡ᷊᷇ͼⱱꜝᴟͼᴠᴢԝ꞊ᴒᴐᴡᴠͼᴟԜꜜᴑꜝꜛ꞉ᴧᴒᴑͼᴡꜝͼᴡⱳᴒͼ᷊᷇᷇ͼꜛⱲͼꜝᴟͼ᷿᷈᷇ͼꜛⱲͼⱫᴅ᷄᷄᷉Ⱡ᷊᷇ͼ
ᴒᴣᴒᴟᴦͼ᷾ͼᴤᴒᴒꞋᴠͼᴡᴟᴒԜᴡꜛᴒꜜᴡͼԜᴟꜛᴠԓͼԜᴐᴐꜝᴟᴑ꞉ꜜⱲͼᴡꜝͼᴡⱳᴒͼᴡԜԝꞌᴒͼⱱꜝᴟͼᴑꜝᴠ꞉ꜜⱲͼᴠᴐⱳᴒᴑᴢꞌᴒ᷅
ⱴꜝᴟͼᴒԜᴐⱳͼꜞꞌԜᴐᴒԝꜝͼᴑꜝᴠᴒԓͼᴒԜᴐⱳͼᴠᴢԝ꞊ᴒᴐᴡͼᴤ꞉ꞌꞌͼᴟᴒᴐᴒ꞉ᴣᴒͼԜͼᴡꜝᴡԜꞌͼꜝⱱͼ᷉ͼꜛꜙԓͼᴑ꞉ᴣ꞉ᴑᴒᴑͼ꞉ꜜᴡꜝͼ᷉ᴠᴒꜞԜᴟԜᴡᴒͼ
᷈᷅᷇ꜛꜙͼᴀⱪͼ꞉ꜜ꞊ᴒᴐᴡ꞉ꜝꜜᴠͼꜝⱱͼꜞꞌԜᴐᴒԝꜝ᷅ͼᴁⱳᴒͼ᷉ͼ꞉ꜜ꞊ᴒᴐᴡ꞉ꜝꜜᴠͼᴤ꞉ꞌꞌͼԝᴒͼⱲ꞉ᴣᴒꜜͼ꞉ꜜͼᴡⱳᴒͼᴠԜꜛᴒͼᴢꜞꜞᴒᴟͼԜᴟꜛԓͼᴤ꞉ᴡⱳͼ
ԜᴡͼꞌᴒԜᴠᴡͼ᷉ͼᴐꜛͼᴠᴒꜞԜᴟԜᴡ꞉ꜝꜜͼԝᴒᴡᴤᴒᴒꜜͼᴒԜᴐⱳͼ꞉ꜜ꞊ᴒᴐᴡ꞉ꜝꜜͼᴠ꞉ᴡᴒ᷅ͼ
Duration of Treatment:
ᴀᴢԝ꞊ᴒᴐᴡᴠͼᴤ꞉ꞌꞌͼᴟᴒᴐᴒ꞉ᴣᴒͼԜͼᴑꜝᴠᴒͼꜝⱱͼԝꞌ꞉ꜜᴑᴒᴑͼⱷꜚ͟ͼᴒᴣᴒᴟᴦͼ᷉ͼᴤᴒᴒꞋᴠͼᴑᴢᴟ꞉ꜜⱲͼᴡⱳᴒͼ᷉⅍᷄ᴤᴒᴒꞋͼᴡᴟᴒԜᴡꜛᴒꜜᴡͼ
ꜞᴒᴟ꞉ꜝᴑͼⱱꜝᴟͼԜͼᴡꜝᴡԜꞌͼꜝⱱͼ᷊᷈ͼᴑꜝᴠᴒᴠ᷅ͼᴁⱳᴒͼⱱ꞉ᴟᴠᴡͼᴑꜝᴠᴒͼꜝⱱͼⱷꜚ͟ͼᴤ꞉ꞌꞌͼԝᴒͼԜᴑꜛ꞉ꜜ꞉ᴠᴡᴒᴟᴒᴑͼꜝꜜͼⱫԜᴦͼ᷇ͼԜꜜᴑͼᴡⱳᴒͼ
ꞌԜᴠᴡͼᴑꜝᴠᴒͼꜝⱱͼⱷꜚ͟ͼᴤ꞉ꞌꞌͼԝᴒͼԜᴑꜛ꞉ꜜ꞉ᴠᴡᴒᴟᴒᴑͼꜝꜜͼⱫԜᴦͼ᷈⅍˲᷅ͼᴁⱳᴒᴟᴒͼᴤ꞉ꞌꞌͼԝᴒͼԜͼᶐ᷊᷄ᴑԜᴦͼᴤ꞉ꜜᴑꜝᴤͼԜᴟꜝᴢꜜᴑͼ
ᴒԜᴐⱳͼᴠᴡᴢᴑᴦͼᴣ꞉ᴠ꞉ᴡԓͼᴤ꞉ᴡⱳͼԜͼꜛԜᴥ꞉ꜛᴢꜛͼꜝⱱͼ᷈ⅎͼᴑԜᴦᴠͼꜝᴟͼԜͼꜛ꞉ꜜ꞉ꜛᴢꜛͼꜝⱱͼ᷈᷈ͼᴑԜᴦᴠͼԝᴒᴡᴤᴒᴒꜜͼԜꜜᴦͼ᷉ͼᴑꜝᴠᴒᴠ᷅ͼ
ᴀᴢԝ꞊ᴒᴐᴡᴠͼᴤ꞉ꞌꞌͼԝᴒͼꜛꜝꜜ꞉ᴡꜝᴟᴒᴑͼԜᴡͼᴡⱳᴒͼᴠᴡᴢᴑᴦͼᴠ꞉ᴡᴒͼᴡⱳᴟꜝᴢⱲⱳͼ᷉ͼⱳꜝᴢᴟᴠͼꜞꜝᴠᴡ᷄ᴑꜝᴠᴒͼⱱꜝᴟͼᴡⱳᴒͼⱱ꞉ᴟᴠᴡͼ᷾ᴑꜝᴠᴒᴠͼ
ᴤ꞉ᴡⱳͼᴡⱳᴒͼԜԝ꞉ꞌ꞉ᴡᴦͼᴡꜝͼᴟᴒᴑᴢᴐᴒͼᴡⱳ꞉ᴠͼᴡ꞉ꜛᴒͼᴡꜝͼ᷈ͼⱳꜝᴢᴟͼⱱꜝᴟͼᴡⱳᴒͼᴟᴒꜛԜ꞉ꜜ꞉ꜜⱲͼᴑꜝᴠᴒᴠͼԝԜᴠᴒᴑͼꜝꜜͼᴡⱳᴒͼᴑ꞉ᴠᴐᴟᴒᴡ꞉ꜝꜜͼ
ꜝⱱͼᴡⱳᴒͼⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟͼԜꜜᴑͼᴡⱳᴒͼԜԝᴠᴒꜜᴐᴒͼꜝⱱͼᴠԜⱱᴒᴡᴦͼᴠ꞉ⱲꜜԜꞌᴠ᷅ͼⱨͼⱱꜝꞌꞌꜝᴤ᷄ᴢꜞͼᴣ꞉ᴠ꞉ᴡͼᴤ꞉ꞌꞌͼꜝᴐᴐᴢᴟͼꜝꜜͼⱫԜᴦͼ᷈˲᷉᷅
Duration of Study for Individual Subjects:
ⱴꜝꞌꞌꜝᴤ꞉ꜜⱲͼ꞉ꜜⱱꜝᴟꜛᴒᴑͼᴐꜝꜜᴠᴒꜜᴡԓͼᴠᴢԝ꞊ᴒᴐᴡᴠͼᴤ꞉ꞌꞌͼᴢꜜᴑᴒᴟⱲꜝͼᴠᴐᴟᴒᴒꜜ꞉ꜜⱲͼԜᴠᴠᴒᴠᴠꜛᴒꜜᴡᴠ᷅ͼᴀᴐᴟᴒᴒꜜᴒᴑͼᴠᴢԝ꞊ᴒᴐᴡᴠͼ
ᴤⱳꜝͼԜᴟᴒͼꜝꜜͼꞌꜝꜜⱲ᷄ᴡᴒᴟꜛͼꜞᴟꜝꜞⱳᴦꞌԜᴐᴡ꞉ᴐͼᴡⱳᴒᴟԜꜞᴦͼⱱꜝᴟⱶⱨⱬͼԜᴟᴒͼᴟᴒꜟᴢ꞉ᴟᴒᴑͼᴡꜝͼᴢꜜᴑᴒᴟⱲꜝͼԜͼꜛ꞉ꜜ꞉ꜛᴢꜛͼ
᷉ᴤᴒᴒꞋͼᴤԜᴠⱳꜝᴢᴡͼꜞᴒᴟ꞉ꜝᴑͼꜞᴟ꞉ꜝᴟͼᴡꜝͼᴡⱳᴒͼᴠᴡԜᴟᴡͼꜝⱱͼᴟᴢꜜ᷄꞉ꜜ᷅ͼᴀᴢԝ꞊ᴒᴐᴡᴠͼᴤⱳꜝͼԜᴟᴒͼᴒ꞉ᴡⱳᴒᴟͼꜜꜝᴡͼꜝꜜͼꞌꜝꜜⱲ᷄ᴡᴒᴟꜛͼ
ꜞᴟꜝꜞⱳᴦꞌԜᴐᴡ꞉ᴐͼᴡⱳᴒᴟԜꜞᴦͼⱱꜝᴟͼⱶⱨⱬԓͼꜝᴟͼⱳԜᴣᴒͼᴐꜝꜛꜞꞌᴒᴡᴒᴑͼᴡⱳᴒͼᴟᴒꜟᴢ꞉ᴟᴒᴑͼᴤԜᴠⱳꜝᴢᴡͼꜞᴒᴟ꞉ꜝᴑԓͼᴤ꞉ꞌꞌͼᴒꜜᴡᴒᴟͼԜͼ
ᴟᴢꜜ᷄꞉ꜜͼꜞᴒᴟ꞉ꜝᴑͼꜝⱱͼ᷾ͼᴤᴒᴒꞋᴠͼᴡꜝͼᴑᴒᴡᴒᴟꜛ꞉ꜜᴒͼᴡⱳᴒͼԝԜᴠᴒꞌ꞉ꜜᴒͼⱶⱨⱬͼԜᴡᴡԜᴐꞋͼᴟԜᴡᴒ᷅ᴁⱳᴒͼᴟᴢꜜ᷄꞉ꜜͼꜞᴒᴟ꞉ꜝᴑͼꜛԜᴦͼ
ꞌԜᴠᴡͼԜᴠͼꞌꜝꜜⱲͼԜᴠͼ˲ͼᴤᴒᴒꞋᴠͼ꞉ꜜͼꜝᴟᴑᴒᴟͼᴡꜝͼꜛᴒᴒᴡͼᴡⱳᴒͼꜛ꞉ꜜ꞉ꜛᴢꜛͼԜᴡᴡԜᴐꞋͼᴟԜᴡᴒͼᴟᴒꜟᴢ꞉ᴟᴒᴑͼⱱꜝᴟͼᴒꜜᴟꜝꞌꞌꜛᴒꜜᴡ᷅ͼ
ⱬꜜᴟꜝꞌꞌᴒᴑͼᴠᴢԝ꞊ᴒᴐᴡᴠͼᴤ꞉ꞌꞌͼᴡⱳᴒꜜͼᴢꜜᴑᴒᴟⱲꜝͼԜͼ᷉⅍᷄ᴤᴒᴒꞋͼᴡᴟᴒԜᴡꜛᴒꜜᴡͼꜞᴒᴟ꞉ꜝᴑ᷅ͼᴀᴢԝ꞊ᴒᴐᴡᴠͼᴤⱳꜝͼᴑꜝͼꜜꜝᴡͼ
ꜞԜᴟᴡ꞉ᴐ꞉ꜞԜᴡᴒͼ꞉ꜜͼᴡⱳᴒͼ꜡ꜙⱬͼᴤ꞉ꞌꞌͼԝᴒͼⱱꜝꞌꞌꜝᴤᴒᴑͼⱱꜝᴟͼԜꜜͼԜᴑᴑ꞉ᴡ꞉ꜝꜜԜꞌͼ˲ͼᴤᴒᴒꞋᴠͼ꞉ꜜͼᴡⱳᴒͼᴑꜝᴢԝꞌᴒ᷄ԝꞌ꞉ꜜᴑͼᴠᴡᴢᴑᴦ᷅
Prohibited Concomitant Treatments:
ᴂᴠᴒͼꜝⱱͼᴡⱳᴒͼⱱꜝꞌꞌꜝᴤ꞉ꜜⱲͼᴡᴟᴒԜᴡꜛᴒꜜᴡᴠͼᴤ꞉ꞌꞌͼꜜꜝᴡͼԝᴒͼꜞᴒᴟꜛ꞉ᴡᴡᴒᴑͼᴑᴢᴟ꞉ꜜⱲͼᴡⱳᴒͼᴠᴡᴢᴑᴦⱡ
ᶄ
ꜙꜝꜜⱲ᷄ᴡᴒᴟꜛͼꜞᴟꜝꜞⱳᴦꞌԜᴥ꞉ᴠͼⱱꜝᴟͼⱶⱨⱬͼӿᴒ᷅Ⱳ᷅ԓͼᴢᴠᴒͼꜝⱱͼⱪ᷈᷄ⱷ꜠ⱶͼⱱꜝᴟͼꞌꜝꜜⱲ᷄ᴡᴒᴟꜛͼꜞᴟꜝꜞⱳᴦꞌԜᴥ꞉ᴠԓͼ
ԜᴡᴡᴒꜜᴢԜᴡᴒᴑͼԜꜜᴑᴟꜝⱲᴒꜜᴠԓͼꜝᴟͼԜꜜᴡ꞉᷄ⱱ꞉ԝᴟ꞉ꜜꜝꞌᴦᴡ꞉ᴐᴠԐ᷅ͼ
ᶄ
ⱨꜜⱲ꞉ꜝᴡᴒꜜᴠ꞉ꜜ᷄ᴐꜝꜜᴣᴒᴟᴡ꞉ꜜⱲͼᴒꜜᴧᴦꜛᴒͼӿⱨⱪⱬԐͼ꞉ꜜⱳ꞉ԝ꞉ᴡꜝᴟᴠ᷅
ᶄ
ⱬᴠᴡᴟꜝⱲᴒꜜ᷄ᴐꜝꜜᴡԜ꞉ꜜ꞉ꜜⱲͼꜛᴒᴑ꞉ᴐԜᴡ꞉ꜝꜜᴠͼᴤ꞉ᴡⱳͼᴠᴦᴠᴡᴒꜛ꞉ᴐͼԜԝᴠꜝᴟꜞᴡ꞉ꜝꜜͼӿᴠᴢᴐⱳͼԜᴠͼꜝᴟԜꞌͼᴐꜝꜜᴡᴟԜᴐᴒꜞᴡ꞉ᴣᴒᴠͼꜝᴟͼ
ⱳꜝᴟꜛꜝꜜԜꞌͼᴟᴒꜞꞌԜᴐᴒꜛᴒꜜᴡͼᴡⱳᴒᴟԜꜞᴦԐ᷅
ᶄ
ⱨꜜᴑᴟꜝⱲᴒꜜᴠͼӿᴒ᷅Ⱳ᷅ԓͼᴠᴡԜꜜꜝᴧꜝꞌꜝꞌԓͼᴑԜꜜԜᴧꜝꞌԓͼꜝᴥԜꜜᴑᴟꜝꞌꜝꜜᴒԓͼꜛᴒᴡⱳᴦꞌᴡᴒᴠᴡꜝᴠᴡᴒᴟꜝꜜᴒԓͼᴡᴒᴠᴡꜝᴠᴡᴒᴟꜝꜜᴒԐ᷅
ᶄ
ⱨꜜᴦͼꜝᴡⱳᴒᴟͼ꞉ꜜᴣᴒᴠᴡ꞉ⱲԜᴡ꞉ꜝꜜԜꞌͼᴑᴟᴢⱲͼꜝᴟͼᴑᴒᴣ꞉ᴐᴒ᷅
ᴁⱳᴒͼᴢᴠᴒͼꜝⱱͼᴠⱳꜝᴟᴡ᷄ᴡᴒᴟꜛͼꜞᴟꜝꜞⱳᴦꞌԜᴐᴡ꞉ᴐͼᴡᴟᴒԜᴡꜛᴒꜜᴡͼⱱꜝᴟͼⱶⱨⱬͼ꞉ᴠͼꜞᴒᴟꜛ꞉ᴡᴡᴒᴑͼ꞉ⱱͼꜛᴒᴑ꞉ᴐԜꞌꞌᴦͼ꞉ꜜᴑ꞉ᴐԜᴡᴒᴑ᷅
Management of Acute Attacks:
ⱨᴐᴢᴡᴒͼⱶⱨⱬͼԜᴡᴡԜᴐꞋᴠͼᴑᴢᴟ꞉ꜜⱲͼᴡⱳᴒͼᴠᴡᴢᴑᴦͼԜᴟᴒͼᴡꜝͼԝᴒͼꜛԜꜜԜⱲᴒᴑͼ꞉ꜜͼԜᴐᴐꜝᴟᴑͼᴤ꞉ᴡⱳͼᴡⱳᴒͼⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟᶳᴠͼ
ᴢᴠᴢԜꞌͼᴐԜᴟᴒͼꜝⱱͼᴡⱳᴒ꞉ᴟͼꜞԜᴡ꞉ᴒꜜᴡᴠԓͼ꞉ꜜᴐꞌᴢᴑ꞉ꜜⱲͼᴢᴠᴒͼꜝⱱͼԜᴐᴢᴡᴒͼԜᴡᴡԜᴐꞋͼᴡⱳᴒᴟԜꜞ꞉ᴒᴠͼᴡⱳԜᴡͼᴡⱳᴒͼⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟͼ
ᴑᴒᴒꜛᴠͼԜᴠͼꜛᴒᴑ꞉ᴐԜꞌꞌᴦͼԜꜞꜞᴟꜝꜞᴟ꞉Ԝᴡᴒ᷅ͼᴂᴠᴒͼꜝⱱͼⱪ᷈᷄ⱷ꜠ⱶͼᴤ꞉ꞌꞌͼԝᴒͼꜞᴒᴟꜛ꞉ᴡᴡᴒᴑͼԜᴠͼԜꜜͼԜᴐᴢᴡᴒͼԜᴡᴡԜᴐꞋͼᴡⱳᴒᴟԜꜞᴦͼ
ԝᴢᴡͼꜜꜝᴡͼԜᴠͼԜͼꞌꜝꜜⱲ᷄ᴡᴒᴟꜛͼꜞᴟꜝꜞⱳᴦꞌԜᴥ꞉ᴠ᷅ͼⱨᴑꜛ꞉ꜜ꞉ᴠᴡᴟԜᴡ꞉ꜝꜜͼꜝⱱͼᴡⱳᴒͼ꞉ꜜᴣᴒᴠᴡ꞉ⱲԜᴡ꞉ꜝꜜԜꞌͼꜞᴟꜝᴑᴢᴐᴡͼԜꜜᴑͼᴠᴡᴢᴑᴦͼ

Ⱬᴅ᷄᷉Ⱡ᷊᷇
ⱪꞌ꞉ꜜ꞉ᴐԜꞌͼᴁᴟ꞉Ԝꞌͼ͟ᴟꜝᴡꜝᴐꜝꞌⱡͼⱫᴅ᷄᷉Ⱡ᷊᷊᷇᷄᷇
ⱨꜛᴒꜜᴑꜛᴒꜜᴡͼ᷊᷅᷇ⱴ꞉ꜜԜꞌⱡͼ᷇ⱠͼꜗԜꜜᴢԜᴟᴦ᷉᷇᷈ⅎ
ⱪꜝꜜⱱ꞉ᴑᴒꜜᴡ꞉Ԝꞌ
͟ԜⱲᴒͼ᷈᷈
ⱫᴦԜᴥͼⱪꜝᴟꜞ᷅
ꜞᴟꜝᴐᴒᴑᴢᴟᴒᴠͼᴤ꞉ꞌꞌͼᴐꜝꜜᴡ꞉ꜜᴢᴒͼᴤ꞉ᴡⱳꜝᴢᴡͼԜꞌᴡᴒᴟԜᴡ꞉ꜝꜜͼᴡꜝͼᴡⱳᴒͼꜞᴟꜝᴡꜝᴐꜝꞌ᷄ᴠꜞᴒᴐ꞉ⱱ꞉ᴒᴑͼᴠᴡᴢᴑᴦͼᴠᴐⱳᴒᴑᴢꞌᴒԓͼᴒᴣᴒꜜͼ꞉ⱱͼ
ᴡⱳᴒͼꜞԜᴡ꞉ᴒꜜᴡͼᴟᴒᴐᴒ꞉ᴣᴒᴠͼԜꜜᴦͼᴡᴟᴒԜᴡꜛᴒꜜᴡͼⱱꜝᴟͼԜꜜͼⱶⱨⱬͼԜᴡᴡԜᴐꞋ᷅
Safety Assessments:
ᴁⱳᴒͼⱱꜝꞌꞌꜝᴤ꞉ꜜⱲͼԜᴠᴠᴒᴠᴠꜛᴒꜜᴡᴠͼᴤ꞉ꞌꞌͼԝᴒͼᴐꜝꜜᴑᴢᴐᴡᴒᴑͼԜᴐᴐꜝᴟᴑ꞉ꜜⱲͼᴡꜝͼᴡⱳᴒͼᴀᴡᴢᴑᴦͼⱨᴐᴡ꞉ᴣ꞉ᴡ꞉ᴒᴠͼᴀᴐⱳᴒᴑᴢꞌᴒⱡ
ᶄ
ⱨᴑᴣᴒᴟᴠᴒͼᴒᴣᴒꜜᴡᴠͼӿⱨⱬᴠԐԓͼ꞉ꜜᴐꞌᴢᴑ꞉ꜜⱲͼᴠᴒᴟ꞉ꜝᴢᴠͼԜᴑᴣᴒᴟᴠᴒͼᴒᴣᴒꜜᴡᴠͼӿᴀⱨⱬᴠԐͼԜꜜᴑͼԜᴑᴣᴒᴟᴠᴒͼᴒᴣᴒꜜᴡᴠͼꜝⱱͼ
ᴠꜞᴒᴐ꞉Ԝꞌͼ꞉ꜜᴡᴒᴟᴒᴠᴡͼӿⱨⱬᴀⱷԐ᷅
ᶄ
ᴃ꞉ᴡԜꞌͼᴠ꞉Ⱳꜜᴠԓͼ꞉ꜜᴐꞌᴢᴑ꞉ꜜⱲͼᴠ꞉ᴡᴡ꞉ꜜⱲͼꜝᴟͼᴠᴢꜞ꞉ꜜᴒͼԝꞌꜝꜝᴑͼꜞᴟᴒᴠᴠᴢᴟᴒͼӿⱩ͟ԐԓͼⱳᴒԜᴟᴡͼᴟԜᴡᴒͼӿⱶϸԐԓͼԝꜝᴑᴦͼ
ᴡᴒꜛꜞᴒᴟԜᴡᴢᴟᴒԓͼԜꜜᴑͼᴟᴒᴠꜞ꞉ᴟԜᴡꜝᴟᴦͼᴟԜᴡᴒͼӿϸϸԐ᷅
ᶄ
͟ⱳᴦᴠ꞉ᴐԜꞌͼᴒᴥԜꜛ꞉ꜜԜᴡ꞉ꜝꜜ᷅
ᶄ
ⱪꞌ꞉ꜜ꞉ᴐԜꞌͼꞌԜԝꜝᴟԜᴡꜝᴟᴦͼᴡᴒᴠᴡ꞉ꜜⱲͼӿⱳᴒꜛԜᴡꜝꞌꜝⱲᴦԓͼᴠᴒᴟᴢꜛͼᴐⱳᴒꜛ꞉ᴠᴡᴟᴦԓͼᴐꜝԜⱲᴢꞌԜᴡ꞉ꜝꜜԓͼԜꜜᴑͼᴢᴟ꞉ꜜԜꞌᴦᴠ꞉ᴠԐ᷅
ᶄ
᷈᷉᷄ꜙᴒԜᴑͼᴒꞌᴒᴐᴡᴟꜝᴐԜᴟᴑ꞉ꜝⱲᴟԜꜛͼӿⱬⱪⱵԐ᷅
Pharmacokinetic (PK) Assessments:
ⱩꞌꜝꜝᴑͼᴠԜꜛꜞꞌᴒᴠͼᴤ꞉ꞌꞌͼԝᴒͼᴐꜝꞌꞌᴒᴐᴡᴒᴑͼⱱꜝᴟͼᴡⱳᴒͼꜛᴒԜᴠᴢᴟᴒꜛᴒꜜᴡͼꜝⱱͼꜞꞌԜᴠꜛԜͼⱫᴅ᷄᷉Ⱡ᷊᷇ͼᴐꜝꜜᴐᴒꜜᴡᴟԜᴡ꞉ꜝꜜᴠͼ
ꜞᴟ꞉ꜝᴟͼᴡꜝͼⱷꜚ͟ͼԜᴑꜛ꞉ꜜ꞉ᴠᴡᴟԜᴡ꞉ꜝꜜͼꜝꜜͼⱫԜᴦͼ᷇ͼԜꜜᴑͼꜝꜜͼⱫԜᴦᴠͼ᷿⅍ᶐ᷊ԓͼⱠ˲ᶐ᷊ԓͼ᷈᷾᷇ᶐ᷊ԓͼԜꜜᴑͼ᷈˲᷉ᶐ᷊᷅ͼ
ⱨᴑᴑ꞉ᴡ꞉ꜝꜜԜꞌͼᴠԜꜛꜞꞌᴒᴠͼᴤ꞉ꞌꞌͼԝᴒͼᴐꜝꞌꞌᴒᴐᴡᴒᴑͼꜝꜜͼⱫԜᴦᴠ᷉᷈᷇ᶐ᷊ͼԜꜜᴑͼ᷊᷉˲ᶐ᷊ͼᴑᴢᴟ꞉ꜜⱲͼᴡⱳᴒͼⱱꜝꞌꞌꜝᴤ᷄ᴢꜞͼꜞᴒᴟ꞉ꜝᴑͼ
ⱱꜝᴟͼԜꜜᴦͼᴠᴢԝ꞊ᴒᴐᴡᴠͼꜜꜝᴡͼᴒꜜᴡᴒᴟ꞉ꜜⱲͼ꜡ꜙⱬ᷅
Pharmacodynamic (PD) Assessments:
ⱩꞌꜝꜝᴑͼᴠԜꜛꜞꞌᴒᴠͼᴤ꞉ꞌꞌͼԝᴒͼᴐꜝꞌꞌᴒᴐᴡᴒᴑͼᴡꜝͼᴒᴣԜꞌᴢԜᴡᴒͼᴡⱳᴒͼꜞⱳԜᴟꜛԜᴐꜝᴑᴦꜜԜꜛ꞉ᴐͼᴒⱱⱱᴒᴐᴡᴠͼꜝⱱͼⱫᴅ᷄᷉Ⱡ᷊᷇ͼ
ᴡⱳᴟꜝᴢⱲⱳͼԝ꞉ꜝꜛԜᴟꞋᴒᴟͼԜᴠᴠԜᴦᴠͼꜞᴟ꞉ꜝᴟͼᴡꜝͼⱷꜚ͟ͼԜᴑꜛ꞉ꜜ꞉ᴠᴡᴟԜᴡ꞉ꜝꜜͼꜝꜜͼⱫԜᴦͼ᷇ͼԜꜜᴑͼꜝꜜͼⱫԜᴦᴠͼ᷿⅍ᶐ᷊ԓͼⱠ˲ᶐ᷊ԓͼ
᷈᷾᷇ᶐ᷊ԓͼԜꜜᴑͼ᷈˲᷉ᶐ᷊᷅ͼⱨᴑᴑ꞉ᴡ꞉ꜝꜜԜꞌͼᴠԜꜛꜞꞌᴒᴠͼᴤ꞉ꞌꞌͼԝᴒͼᴐꜝꞌꞌᴒᴐᴡᴒᴑͼꜝꜜͼⱫԜᴦᴠͼ᷉᷈᷇ᶐ᷊ͼԜꜜᴑͼ᷊᷉˲ᶐ᷊ͼᴑᴢᴟ꞉ꜜⱲͼ
ᴡⱳᴒͼⱱꜝꞌꞌꜝᴤ᷄ᴢꜞͼꜞᴒᴟ꞉ꜝᴑͼⱱꜝᴟͼԜꜜᴦͼᴠᴢԝ꞊ᴒᴐᴡᴠͼꜜꜝᴡͼᴒꜜᴡᴒᴟ꞉ꜜⱲͼ꜡ꜙⱬ᷅
Immunogenicity Assessments:
ⱩꞌꜝꜝᴑͼᴠԜꜛꜞꞌᴒᴠͼᴤ꞉ꞌꞌͼԝᴒͼᴐꜝꞌꞌᴒᴐᴡᴒᴑͼᴡꜝͼԜᴠᴠԜᴦͼⱱꜝᴟͼᴡⱳᴒͼꜞᴟᴒᴠᴒꜜᴐᴒͼꜝⱱͼԜꜜᴡ꞉᷄ᴑᴟᴢⱲͼԜꜜᴡ꞉ԝꜝᴑ꞉ᴒᴠԓͼ꞉ꜜᴐꞌᴢᴑ꞉ꜜⱲͼ
ᴒᴣԜꞌᴢԜᴡ꞉ꜝꜜͼꜝⱱͼꜜᴒᴢᴡᴟԜꞌ꞉ᴧ꞉ꜜⱲͼԜꜜᴡ꞉ԝꜝᴑ꞉ᴒᴠͼӿ꞉ⱱͼԜꜜᴦͼᴐꜝꜜⱱ꞉ᴟꜛᴒᴑͼꜞꜝᴠ꞉ᴡ꞉ᴣᴒͼԜꜜᴡ꞉᷄ᴑᴟᴢⱲͼԜꜜᴡ꞉ԝꜝᴑ꞉ᴒᴠͼԜᴟᴒͼ
ᴑᴒᴡᴒᴐᴡᴒᴑԐͼꜞᴟ꞉ꜝᴟͼᴡꜝͼⱷꜚ͟ͼԜᴑꜛ꞉ꜜ꞉ᴠᴡᴟԜᴡ꞉ꜝꜜͼꜝꜜͼⱫԜᴦͼ᷇ͼԜꜜᴑͼꜝꜜͼⱫԜᴦᴠͼ᷿⅍ᶐ᷊ԓͼⱠ˲ᶐ᷊ԓͼ᷈᷾᷇ᶐ᷊ԓͼԜꜜᴑͼ᷈˲᷉ᶐ᷊᷅ͼ
ⱨᴑᴑ꞉ᴡ꞉ꜝꜜԜꞌͼᴠԜꜛꜞꞌᴒᴠͼᴤ꞉ꞌꞌͼԝᴒͼᴐꜝꞌꞌᴒᴐᴡᴒᴑͼꜝꜜⱫԜᴦͼ᷊᷉˲ᶐ᷊ͼᴑᴢᴟ꞉ꜜⱲͼᴡⱳᴒͼⱱꜝꞌꞌꜝᴤ᷄ᴢꜞͼꜞᴒᴟ꞉ꜝᴑͼⱱꜝᴟͼԜꜜᴦͼ
ᴠᴢԝ꞊ᴒᴐᴡᴠͼꜜꜝᴡͼᴒꜜᴡᴒᴟ꞉ꜜⱲͼ꜡ꜙⱬ᷅
C1-INH, C4, and C1q Assessments:
ᴀԜꜛꜞꞌᴒᴠͼⱱꜝᴟͼⱪ᷈᷄ⱷ꜠ⱶԓͼⱪ᷾ԓͼԜꜜᴑͼⱪ᷈ꜟͼԜᴠᴠԜᴦᴠͼᴤ꞉ꞌꞌͼԝᴒͼꜝԝᴡԜ꞉ꜜᴒᴑͼԜᴡͼᴠᴐᴟᴒᴒꜜ꞉ꜜⱲͼⱱꜝᴟͼᴒꞌ꞉Ⱳ꞉ԝ꞉ꞌ꞉ᴡᴦͼ
Ԝᴠᴠᴒᴠᴠꜛᴒꜜᴡ᷅ͼ
Quality of Life Assessments:
ϷᴢԜꞌ꞉ᴡᴦ᷄ꜝⱱ᷄ꞌ꞉ⱱᴒͼӿϷꜝꜙԐͼᴑԜᴡԜͼᴤ꞉ꞌꞌͼԝᴒͼꜝԝᴡԜ꞉ꜜᴒᴑͼᴢᴠ꞉ꜜⱲͼᴡⱳᴒͼⱬᴢᴟꜝϷꜝꜙͼⱵᴟꜝᴢꜞͼ᷿᷄Ⱬ꞉ꜛᴒꜜᴠ꞉ꜝꜜͼӿⱬϷ᷿ⱫԐͼ
Ϸᴢᴒᴠᴡ꞉ꜝꜜꜜԜ꞉ᴟᴒͼԜᴡͼꜞᴟᴒ᷄ᴑꜝᴠᴒͼꜝꜜͼⱫԜᴦᴠͼ᷇ԓͼⱠ˲ᶐ᷊ԓͼԜꜜᴑͼ᷈˲᷉ᶐ᷊ͼԜꜜᴑͼᴢᴠ꞉ꜜⱲͼᴡⱳᴒͼⱨꜜⱲ꞉ꜝᴒᴑᴒꜛԜ᷄ϷᴢԜꞌ꞉ᴡᴦͼꜝⱱͼ
ꜙ꞉ⱱᴒͼӿⱨⱬ᷄ϷꜝꜙԐͼϷᴢᴒᴠᴡ꞉ꜝꜜꜜԜ꞉ᴟᴒͼԜᴡͼꜞᴟᴒ᷄ᴑꜝᴠᴒͼꜝꜜͼⱫԜᴦᴠͼ᷇ԓͼ᷉˲ͼᶐ᷊ԓͼ᷿⅍ᶐ᷊ԓͼⱠ˲ᶐ᷊ԓ ᷈᷉⅍ͼᶐ᷊ԓͼ᷿᷈᷾ͼᶐ᷊ԓͼ
Ԝꜜᴑͼ᷈˲᷉ᶐ᷊᷅ͼⱨꜜԜᴑᴑ꞉ᴡ꞉ꜝꜜԜꞌͼϷꜝꜙͼԜᴠᴠᴒᴠᴠꜛᴒꜜᴡͼᴤ꞉ꞌꞌͼԝᴒͼᴐꜝꜜᴑᴢᴐᴡᴒᴑͼꜝꜜͼⱫԜᴦ᷊᷉˲ᶐ᷊ͼⱱꜝᴟͼᴠᴢԝ꞊ᴒᴐᴡᴠͼꜜꜝᴡͼ
ᴒꜜᴡᴒᴟ꞉ꜜⱲͼ꜡ꜙⱬ᷅ͼ
Collection of HAE Attack Data:
ᴁⱳᴒͼᴐꜝꞌꞌᴒᴐᴡ꞉ꜝꜜԓͼᴟᴒꜞꜝᴟᴡ꞉ꜜⱲͼԜꜜᴑͼԜᴠᴠᴒᴠᴠꜛᴒꜜᴡͼꜝⱱͼԜᴡᴡԜᴐꞋᴠͼ꞉ꜜͼᴡⱳ꞉ᴠͼᴠᴡᴢᴑᴦͼᴤ꞉ꞌꞌͼԝᴒͼᴑꜝꜜᴒͼ꞉ꜜͼԜᴐᴐꜝᴟᴑԜꜜᴐᴒͼ

Ⱬᴅ᷄᷉Ⱡ᷊᷇
ⱪꞌ꞉ꜜ꞉ᴐԜꞌͼᴁᴟ꞉Ԝꞌͼ͟ᴟꜝᴡꜝᴐꜝꞌⱡͼⱫᴅ᷄᷉Ⱡ᷊᷊᷇᷄᷇
ⱨꜛᴒꜜᴑꜛᴒꜜᴡͼ᷊᷅᷇ⱴ꞉ꜜԜꞌⱡͼ᷇ⱠͼꜗԜꜜᴢԜᴟᴦ᷉᷇᷈ⅎ
ⱪꜝꜜⱱ꞉ᴑᴒꜜᴡ꞉Ԝꞌ
͟ԜⱲᴒͼ᷈᷉
ⱫᴦԜᴥͼⱪꜝᴟꜞ᷅
ᴤ꞉ᴡⱳͼᴡⱳᴒͼⱶⱨⱬͼⱨᴡᴡԜᴐꞋͼⱨᴠᴠᴒᴠᴠꜛᴒꜜᴡͼԜꜜᴑͼϸᴒꜞꜝᴟᴡ꞉ꜜⱲͼ͟ᴟꜝᴐᴒᴑᴢᴟᴒᴠͼӿⱶⱨⱨϸ͟Ԑ᷅ͼᴀ꞉ᴡᴒͼꜞᴒᴟᴠꜝꜜꜜᴒꞌͼᴤ꞉ꞌꞌͼ
ԝᴒͼᴡᴟԜ꞉ꜜᴒᴑͼꜝꜜͼⱶⱨⱨϸ͟ͼꜞᴟ꞉ꜝᴟͼᴡꜝͼᴠᴐᴟᴒᴒꜜ꞉ꜜⱲͼᴠᴢԝ꞊ᴒᴐᴡᴠͼԜᴡͼᴡⱳᴒ꞉ᴟͼᴠ꞉ᴡᴒ᷅
Ⱬᴢᴟ꞉ꜜⱲͼᴠᴐᴟᴒᴒꜜ꞉ꜜⱲԓͼᴠ꞉ᴡᴒͼꜞᴒᴟᴠꜝꜜꜜᴒꞌͼᴤ꞉ꞌꞌͼᴡᴟԜ꞉ꜜͼᴠᴢԝ꞊ᴒᴐᴡᴠͼԜꜜᴑͼᴐԜᴟᴒⱲ꞉ᴣᴒᴟᴠͼꜝꜜͼ꞉ᴑᴒꜜᴡ꞉ⱱᴦ꞉ꜜⱲͼᴠᴦꜛꜞᴡꜝꜛᴠͼ
ꜝⱱͼԜꜜͼԜᴡᴡԜᴐꞋԓͼᴡⱳᴒͼᴟᴒꜟᴢ꞉ᴟᴒꜛᴒꜜᴡᴠͼⱱꜝᴟͼᴟᴒꜞꜝᴟᴡ꞉ꜜⱲͼԜᴡᴡԜᴐꞋᴠͼԜꜜᴑͼᴡⱳᴒͼ꞉ꜜⱱꜝᴟꜛԜᴡ꞉ꜝꜜͼᴡⱳᴒᴦͼᴤ꞉ꞌꞌͼԝᴒͼᴒᴥꜞᴒᴐᴡᴒᴑͼ
ᴡꜝͼꜞᴟꜝᴣ꞉ᴑᴒ᷅ͼᴁⱳᴒͼᴠᴢԝ꞊ᴒᴐᴡͼӿԜꜜᴑͼᴐԜᴟᴒⱲ꞉ᴣᴒᴟԐͼᴤ꞉ꞌꞌͼᴐꜝꜜⱱ꞉ᴟꜛͼᴡⱳᴒ꞉ᴟͼᴢꜜᴑᴒᴟᴠᴡԜꜜᴑ꞉ꜜⱲͼꜝⱱͼᴤⱳԜᴡͼ꞉ᴠͼᴟᴒꜟᴢ꞉ᴟᴒᴑͼ
ꜝⱱͼᴡⱳᴒꜛͼⱱꜝᴟͼᴟᴒꜞꜝᴟᴡ꞉ꜜⱲͼԜᴡᴡԜᴐꞋᴠͼᴡꜝͼᴡⱳᴒͼᴠ꞉ᴡᴒ᷅
ⱨᴡͼᴠᴐᴟᴒᴒꜜ꞉ꜜⱲԓͼᴠᴢԝ꞊ᴒᴐᴡͼⱶⱨⱬͼԜᴡᴡԜᴐꞋͼⱳ꞉ᴠᴡꜝᴟᴦͼᴤ꞉ꞌꞌͼԝᴒͼᴐꜝꞌꞌᴒᴐᴡᴒᴑ᷅ͼⱷꜜⱱꜝᴟꜛԜᴡ꞉ꜝꜜͼᴐꜝꞌꞌᴒᴐᴡᴒᴑͼᴤ꞉ꞌꞌͼ꞉ꜜᴐꞌᴢᴑᴒͼ
Ԝꜜᴦͼꜞᴟ꞉ꜝᴟͼⱳ꞉ᴠᴡꜝᴟᴦͼꜝⱱͼꞌԜᴟᴦꜜⱲᴒԜꞌͼԜᴡᴡԜᴐꞋᴠԓͼԜᴡᴡԜᴐꞋͼⱱᴟᴒꜟᴢᴒꜜᴐᴦԓͼԜᴣᴒᴟԜⱲᴒͼᴠᴒᴣᴒᴟ꞉ᴡᴦԓͼꜞᴟᴒᴑꜝꜛ꞉ꜜԜꜜᴡͼԜᴡᴡԜᴐꞋͼ
ꞌꜝᴐԜᴡ꞉ꜝꜜӿᴠԐԓͼԜᴣᴒᴟԜⱲᴒͼᴑᴢᴟԜᴡ꞉ꜝꜜԓͼԜᴐᴢᴡᴒͼԜᴡᴡԜᴐꞋͼᴡⱳᴒᴟԜꜞᴦͼᴢᴠᴒԓͼԜꜜᴑͼⱳ꞉ᴠᴡꜝᴟᴦͼꜝⱱͼꞌꜝꜜⱲ᷄ᴡᴒᴟꜛͼꜞᴟꜝꜞⱳᴦꞌԜᴥ꞉ᴠ᷅
Ⱬᴢᴟ꞉ꜜⱲͼᴡⱳᴒͼᴠᴡᴢᴑᴦԓͼᴠᴢԝ꞊ᴒᴐᴡᴠͼӿꜝᴟͼᴐԜᴟᴒⱲ꞉ᴣᴒᴟᴠԐͼᴤ꞉ꞌꞌͼԝᴒͼ꞉ꜜᴠᴡᴟᴢᴐᴡᴒᴑͼᴡꜝͼꜜꜝᴡ꞉ⱱᴦͼԜꜜᴑͼᴟᴒꜞꜝᴟᴡͼᴑᴒᴡԜ꞉ꞌᴠͼᴡꜝͼᴡⱳᴒͼ
ᴠᴡᴢᴑᴦͼᴠ꞉ᴡᴒͼᴤ꞉ᴡⱳ꞉ꜜͼⅎ᷉ͼⱳꜝᴢᴟᴠͼꜝⱱͼᴡⱳᴒͼꜝꜜᴠᴒᴡͼꜝⱱͼԜꜜͼⱶⱨⱬͼԜᴡᴡԜᴐꞋ᷅ͼⱷꜜͼᴡⱳᴒͼᴠ꞉ᴡᴢԜᴡ꞉ꜝꜜͼᴡⱳԜᴡͼԜͼᴠᴢԝ꞊ᴒᴐᴡͼ꞉ᴠͼ
꞉ꜜᴐԜꜞԜᴐ꞉ᴡԜᴡᴒᴑͼⱱꜝꞌꞌꜝᴤ꞉ꜜⱲͼԜꜜͼԜᴡᴡԜᴐꞋԓͼᴡⱳ꞉ᴠͼ꞉ꜜⱱꜝᴟꜛԜᴡ꞉ꜝꜜͼᴐԜꜜͼԝᴒͼꜞᴟꜝᴣ꞉ᴑᴒᴑͼᴡꜝͼᴡⱳᴒͼᴠ꞉ᴡᴒͼԝᴦͼԜͼⱱԜꜛ꞉ꞌᴦͼ
ꜛᴒꜛԝᴒᴟͼꜝᴟͼꜝᴡⱳᴒᴟͼ꞉ꜜᴑ꞉ᴣ꞉ᴑᴢԜꞌᴤ꞉ᴡⱳͼᴑᴒᴡԜ꞉ꞌᴒᴑͼꞋꜜꜝᴤꞌᴒᴑⱲᴒͼꜝⱱͼᴡⱳᴒͼᴒᴣᴒꜜᴡ᷅ͼⱷⱱͼᴑᴒᴠ꞉ᴟᴒᴑͼԝᴦͼᴡⱳᴒͼᴠᴢԝ꞊ᴒᴐᴡԓͼ
ꜛᴒꜛꜝᴟᴦͼԜ꞉ᴑᴠͼꜛԜᴦͼԝᴒͼꜞᴟꜝᴣ꞉ᴑᴒᴑͼᴡꜝͼԜᴠᴠ꞉ᴠᴡͼ꞉ꜜͼᴡᴟԜᴐꞋ꞉ꜜⱲͼԜꜜᴦͼⱶⱨⱬͼԜᴡᴡԜᴐꞋᴠͼᴠᴢԝ꞊ᴒᴐᴡᴠͼᴒᴥꜞᴒᴟ꞉ᴒꜜᴐᴒ᷅ͼ
ᴄᴒᴒꞋꞌᴦͼᴐꜝꜛꜛᴢꜜ꞉ᴐԜᴡ꞉ꜝꜜͼԝᴒᴡᴤᴒᴒꜜͼᴡⱳᴒͼꜞԜᴡ꞉ᴒꜜᴡᴠͼԜꜜᴑͼᴡⱳᴒͼᴠ꞉ᴡᴒԓͼ꞉ꜜᴐꞌᴢᴑ꞉ꜜⱲͼᴟᴒꜞꜝᴟᴡᴠͼꜝⱱͼⱶⱨⱬͼԜᴡᴡԜᴐꞋᴠԓͼ
ꜛᴢᴠᴡͼԝᴒͼᴑꜝᴐᴢꜛᴒꜜᴡᴒᴑͼ꞉ꜜͼᴡⱳᴒͼᴒⱪϸⱴ᷅
ᴀᴢԝ꞊ᴒᴐᴡᴠͼӿꜝᴟͼᴐԜᴟᴒⱲ꞉ᴣᴒᴟᴠԐͼᴤ꞉ꞌꞌͼԝᴒͼԜᴠꞋᴒᴑͼᴡꜝͼꜞᴟꜝᴣ꞉ᴑᴒͼᴡⱳᴒͼⱱꜝꞌꞌꜝᴤ꞉ꜜⱲͼ꞉ꜜⱱꜝᴟꜛԜᴡ꞉ꜝꜜͼᴤⱳᴒꜜͼᴟᴒꜞꜝᴟᴡ꞉ꜜⱲͼԜꜜͼ
ԜᴡᴡԜᴐꞋⱡ

ⱫԜᴡᴒͼԜꜜᴑͼᴡ꞉ꜛᴒͼᴠᴦꜛꜞᴡꜝꜛᴠͼꜝⱱͼԜꜜͼԜᴡᴡԜᴐꞋͼᴤᴒᴟᴒͼⱱ꞉ᴟᴠᴡͼᴒᴥꜞᴒᴟ꞉ᴒꜜᴐᴒᴑ

Ⱬᴒᴠᴐᴟ꞉ꜞᴡ꞉ꜝꜜͼꜝⱱͼᴠᴦꜛꜞᴡꜝꜛᴠͼᴒᴥꜞᴒᴟ꞉ᴒꜜᴐᴒᴑԓͼ꞉ꜜᴐꞌᴢᴑ꞉ꜜⱲͼꞌꜝᴐԜᴡ꞉ꜝꜜӿᴠԐ

ⱷꜛꜞԜᴐᴡͼꜝꜜͼԜᴐᴡ꞉ᴣ꞉ᴡᴦͼԜꜜᴑͼᴤⱳᴒᴡⱳᴒᴟͼԜꜜᴦͼԜᴠᴠ꞉ᴠᴡԜꜜᴐᴒͼꜝᴟͼꜛᴒᴑ꞉ᴐԜꞌͼ꞉ꜜᴡᴒᴟᴣᴒꜜᴡ꞉ꜝꜜͼᴤԜᴠͼᴟᴒꜟᴢ꞉ᴟᴒᴑԓͼ
꞉ꜜᴐꞌᴢᴑ꞉ꜜⱲͼⱳꜝᴠꜞ꞉ᴡԜꞌ꞉ᴧԜᴡ꞉ꜝꜜᴠͼꜝᴟͼᴒꜛᴒᴟⱲᴒꜜᴐᴦͼᴑᴒꜞԜᴟᴡꜛᴒꜜᴡͼᴣ꞉ᴠ꞉ᴡᴠ

ⱨꜜᴦͼꜛᴒᴑ꞉ᴐԜᴡ꞉ꜝꜜᴠͼᴢᴠᴒᴑͼᴡꜝͼᴡᴟᴒԜᴡͼᴡⱳᴒͼԜᴡᴡԜᴐꞋ

ⱷⱱͼᴡⱳᴒͼԜᴡᴡԜᴐꞋͼᴟᴒᴠꜝꞌᴣᴒᴑԓͼᴑԜᴡᴒͼԜꜜᴑͼᴡ꞉ꜛᴒͼᴡⱳᴒͼᴠᴢԝ꞊ᴒᴐᴡͼᴤԜᴠͼꜜꜝͼꞌꜝꜜⱲᴒᴟͼᴒᴥꜞᴒᴟ꞉ᴒꜜᴐ꞉ꜜⱲͼᴠᴦꜛꜞᴡꜝꜛᴠ
ᴀ꞉ᴡᴒͼꜞᴒᴟᴠꜝꜜꜜᴒꞌͼᴤ꞉ꞌꞌͼᴟᴒᴣ꞉ᴒᴤͼᴡⱳᴒͼ꞉ꜜⱱꜝᴟꜛԜᴡ꞉ꜝꜜͼꜞᴟꜝᴣ꞉ᴑᴒᴑͼԜꜜᴑͼᴠꜝꞌ꞉ᴐ꞉ᴡͼԜᴑᴑ꞉ᴡ꞉ꜝꜜԜꞌͼ꞉ꜜⱱꜝᴟꜛԜᴡ꞉ꜝꜜͼԜᴠͼ
ꜜᴒᴐᴒᴠᴠԜᴟᴦͼᴡꜝͼᴑꜝᴐᴢꜛᴒꜜᴡͼᴡⱳᴒͼԜᴡᴡԜᴐꞋԓͼԜᴠͼᴑᴒᴠᴐᴟ꞉ԝᴒᴑͼ꞉ꜜͼᴡⱳᴒͼⱶⱨⱨϸ᷅͟ͼ
ᴀ꞉ᴡᴒͼꜞᴒᴟᴠꜝꜜꜜᴒꞌͼᴤ꞉ꞌꞌͼᴐꜝꜜᴡԜᴐᴡͼᴡⱳᴒͼᴠᴢԝ꞊ᴒᴐᴡͼꜝᴟͼᴐԜᴟᴒⱲ꞉ᴣᴒᴟͼꜝꜜͼԜͼᴤᴒᴒꞋꞌᴦͼԝԜᴠ꞉ᴠͼꜝᴟͼԜꜞꜞᴟꜝᴥ꞉ꜛԜᴡᴒꞌᴦͼⅎᴑԜᴦᴠͼ
ԜⱱᴡᴒᴟͼꞌԜᴠᴡͼᴐꜝꜜᴡԜᴐᴡͼᴤ꞉ᴡⱳͼᴡⱳᴒͼᴠᴢԝ꞊ᴒᴐᴡͼᴡⱳᴟꜝᴢⱲⱳꜝᴢᴡͼᴡⱳᴒͼᴟᴢꜜ᷄꞉ꜜͼꜞᴒᴟ꞉ꜝᴑ᷅ͼⱷⱱͼᴡⱳᴒͼᴠᴢԝ꞊ᴒᴐᴡͼᴒᴥꜞᴒᴟ꞉ᴒꜜᴐᴒᴠͼ᷈ͼꜝᴟͼ
ꜛꜝᴟᴒͼⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟ᷄ᴐꜝꜜⱱ꞉ᴟꜛᴒᴑͼⱶⱨⱬͼԜᴡᴡԜᴐꞋᴠͼԝᴦͼᴒꜜᴑͼꜝⱱͼᴤᴒᴒꞋ᷾ԓͼᴡⱳᴒͼᴠᴢԝ꞊ᴒᴐᴡͼᴤ꞉ꞌꞌͼⱳԜᴣᴒͼⱱᴢꞌⱱ꞉ꞌꞌᴒᴑͼ
ᴡⱳᴒͼᴟᴢꜜ᷄꞉ꜜͼᴟᴒꜟᴢ꞉ᴟᴒꜛᴒꜜᴡͼԜꜜᴑͼꜛԜᴦͼꜞᴟꜝᴐᴒᴒᴑͼᴡꜝͼᴒꜜᴟꜝꞌꞌꜛᴒꜜᴡͼԜꜜᴑͼᴟԜꜜᴑꜝꜛ꞉ᴧԜᴡ꞉ꜝꜜ᷅ͼᴀᴢԝ꞊ᴒᴐᴡᴠͼᴤⱳꜝͼ
ᴒᴥꜞᴒᴟ꞉ᴒꜜᴐᴒͼ᷊ͼꜝᴟͼꜛꜝᴟᴒͼⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟ᷄ᴐꜝꜜⱱ꞉ᴟꜛᴒᴑͼԜᴡᴡԜᴐꞋᴠͼᴐԜꜜͼᴒᴥ꞉ᴡͼᴡⱳᴒͼᴟᴢꜜ᷄꞉ꜜͼꜞᴒᴟ꞉ꜝᴑͼᴒԜᴟꞌᴦͼԜꜜᴑͼ
ꜞᴟꜝᴐᴒᴒᴑͼᴡꜝͼᴒꜜᴟꜝꞌꞌꜛᴒꜜᴡͼԜꜜᴑͼᴟԜꜜᴑꜝꜛ꞉ᴧԜᴡ꞉ꜝꜜ᷅ͼⱷⱱͼᴡⱳᴒͼᴠᴢԝ꞊ᴒᴐᴡͼᴒᴥꜞᴒᴟ꞉ᴒꜜᴐᴒᴠͼꜜꜝͼⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟ᷄
ᴐꜝꜜⱱ꞉ᴟꜛᴒᴑͼⱶⱨⱬͼԜᴡᴡԜᴐꞋᴠͼԝᴦͼᴡⱳᴒͼᴒꜜᴑͼꜝⱱͼᴤᴒᴒꞋͼ᷾ԓͼᴡⱳᴒͼᴠᴢԝ꞊ᴒᴐᴡͼᴤ꞉ꞌꞌͼᴟᴒꜛԜ꞉ꜜͼ꞉ꜜͼᴡⱳᴒͼᴟᴢꜜ᷄꞉ꜜͼꜞᴒᴟ꞉ꜝᴑͼⱱꜝᴟͼ
ԜꜜͼԜᴑᴑ꞉ᴡ꞉ꜝꜜԜꞌͼ᷾ᴤᴒᴒꞋᴠ᷅ͼᴁⱳᴒͼꜛԜᴥ꞉ꜛᴢꜛͼᴑᴢᴟԜᴡ꞉ꜝꜜͼꜝⱱͼᴡⱳᴒͼᴟᴢꜜ᷄꞉ꜜͼꜞᴒᴟ꞉ꜝᴑͼ꞉ᴠͼ˲ͼᴤᴒᴒꞋᴠ᷅ⱷⱱͼᴟᴢꜜ᷄꞉ꜜͼⱳԜᴠͼ
ԝᴒᴒꜜͼᴒᴥᴡᴒꜜᴑᴒᴑͼԜꜜᴑͼᴡⱳᴒͼᴠᴢԝ꞊ᴒᴐᴡͼⱳԜᴠͼ᷉ͼꜝᴟͼꜛꜝᴟᴒͼⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟ᷄ᴐꜝꜜⱱ꞉ᴟꜛᴒᴑͼⱶⱨⱬͼԜᴡᴡԜᴐꞋᴠͼԝᴦͼᴡⱳᴒͼᴒꜜᴑͼ
ꜝⱱͼᴤᴒᴒꞋͼ˲ԓͼᴡⱳᴒͼᴠᴢԝ꞊ᴒᴐᴡͼᴤ꞉ꞌꞌͼⱳԜᴣᴒͼⱱᴢꞌⱱ꞉ꞌꞌᴒᴑͼᴡⱳᴒͼᴟᴢꜜ᷄꞉ꜜᴟᴒꜟᴢ꞉ᴟᴒꜛᴒꜜᴡͼԜꜜᴑͼꜛԜᴦͼꜞᴟꜝᴐᴒᴒᴑͼᴡꜝͼᴡⱳᴒͼ
ᴑꜝᴢԝꞌᴒ᷄ԝꞌ꞉ꜜᴑͼᴡᴟᴒԜᴡꜛᴒꜜᴡͼꜞᴒᴟ꞉ꜝᴑ᷅ͼᴁꜝͼԝᴒͼᴒꞌ꞉Ⱳ꞉ԝꞌᴒͼⱱꜝᴟͼᴒꜜᴟꜝꞌꞌꜛᴒꜜᴡԓͼᴠᴢԝ꞊ᴒᴐᴡᴠͼᴤⱳꜝͼⱳԜᴣᴒͼᴡⱳᴒ꞉ᴟͼᴟᴢꜜ᷄꞉ꜜͼ
ᴒᴥᴡᴒꜜᴑᴒᴑͼꜛᴢᴠᴡͼᴐꜝꜛꜞꞌᴒᴡᴒͼᴡⱳᴒͼⱱᴢꞌꞌͼ˲᷄ᴤᴒᴒꞋͼᴟᴢꜜ᷄꞉ꜜͼꜞᴒᴟ꞉ꜝᴑͼꜞᴟ꞉ꜝᴟͼᴡꜝͼᴒꜜᴡᴒᴟ꞉ꜜⱲͼᴡⱳᴒͼᴡᴟᴒԜᴡꜛᴒꜜᴡͼꜞᴒᴟ꞉ꜝᴑ᷅ͼ
ᴀᴢԝ꞊ᴒᴐᴡᴠͼᴤⱳꜝͼᴑꜝͼꜜꜝᴡͼꜛᴒᴒᴡͼᴡⱳᴒͼꜛ꞉ꜜ꞉ꜛᴢꜛͼԜᴡᴡԜᴐꞋͼᴟԜᴡᴒͼᴑᴢᴟ꞉ꜜⱲͼᴟᴢꜜ᷄꞉ꜜͼᴤ꞉ꞌꞌͼԝᴒͼᴐꜝꜜᴠ꞉ᴑᴒᴟᴒᴑͼԜͼᴠᴐᴟᴒᴒꜜͼ
ⱱԜ꞉ꞌ᷅ͼ
Ⱬᴢᴟ꞉ꜜⱲͼᴡⱳᴒͼᴡᴟᴒԜᴡꜛᴒꜜᴡͼꜞᴒᴟ꞉ꜝᴑͼᴠ꞉ᴡᴒͼꜞᴒᴟᴠꜝꜜꜜᴒꞌͼᴤ꞉ꞌꞌͼᴐꜝꜜᴡԜᴐᴡͼᴡⱳᴒͼᴠᴢԝ꞊ᴒᴐᴡͼꜝᴟͼᴐԜᴟᴒⱲ꞉ᴣᴒᴟͼꜝꜜᴐᴒͼԝᴒᴡᴤᴒᴒꜜͼ
ᴠᴐⱳᴒᴑᴢꞌᴒᴑͼᴠᴡᴢᴑᴦͼᴣ꞉ᴠ꞉ᴡᴠͼꜝᴟͼԜꜞꜞᴟꜝᴥ꞉ꜛԜᴡᴒꞌᴦͼⅎͼᴑԜᴦᴠͼԜⱱᴡᴒᴟͼꞌԜᴠᴡͼᴐꜝꜜᴡԜᴐᴡͼᴡꜝͼᴠꜝꞌ꞉ᴐ꞉ᴡͼⱱꜝᴟͼԜꜜᴦͼⱶⱨⱬͼԜᴡᴡԜᴐꞋͼ

Ⱬᴅ᷄᷉Ⱡ᷊᷇
ⱪꞌ꞉ꜜ꞉ᴐԜꞌͼᴁᴟ꞉Ԝꞌͼ͟ᴟꜝᴡꜝᴐꜝꞌⱡͼⱫᴅ᷄᷉Ⱡ᷊᷊᷇᷄᷇
ⱨꜛᴒꜜᴑꜛᴒꜜᴡͼ᷊᷅᷇ⱴ꞉ꜜԜꞌⱡͼ᷇ⱠͼꜗԜꜜᴢԜᴟᴦ᷉᷇᷈ⅎ
ⱪꜝꜜⱱ꞉ᴑᴒꜜᴡ꞉Ԝꞌ
͟ԜⱲᴒͼ᷊᷈
ⱫᴦԜᴥͼⱪꜝᴟꜞ᷅
꞉ꜜⱱꜝᴟꜛԜᴡ꞉ꜝꜜͼꜜꜝᴡͼԜꞌᴟᴒԜᴑᴦͼᴟᴒꜞꜝᴟᴡᴒᴑ᷅
ᴁⱳᴟꜝᴢⱲⱳꜝᴢᴡͼᴡⱳᴒͼᴑᴢᴟԜᴡ꞉ꜝꜜͼꜝⱱͼᴡⱳᴒͼᴑꜝᴢԝꞌᴒ᷄ԝꞌ꞉ꜜᴑͼᴠᴡᴢᴑᴦԓͼᴑᴢᴟ꞉ꜜⱲͼᴒԜᴐⱳͼᴠᴡᴢᴑᴦͼᴣ꞉ᴠ꞉ᴡͼԜᴡͼᴡⱳᴒͼ꞉ꜜᴣᴒᴠᴡ꞉ⱲԜᴡ꞉ᴣᴒͼ
ᴠ꞉ᴡᴒԓͼᴠ꞉ᴡᴒͼꜞᴒᴟᴠꜝꜜꜜᴒꞌͼᴤ꞉ꞌꞌͼᴠꜝꞌ꞉ᴐ꞉ᴡͼⱱꜝᴟͼԜꜜᴦͼꜜᴒᴤͼⱶⱨⱬͼԜᴡᴡԜᴐꞋͼ꞉ꜜⱱꜝᴟꜛԜᴡ꞉ꜝꜜͼᴡⱳԜᴡͼᴤԜᴠͼꜜꜝᴡͼԜꞌᴟᴒԜᴑᴦͼ
ꜞᴟꜝᴣ꞉ᴑᴒᴑͼᴡꜝͼᴡⱳᴒͼᴠ꞉ᴡᴒ᷅
ⱷꜜͼᴡⱳ꞉ᴠͼᴠᴡᴢᴑᴦͼⱶⱨⱬͼԜᴡᴡԜᴐꞋᴠͼᴤ꞉ꞌꞌͼԝᴒͼᴐԜꜞᴡᴢᴟᴒᴑͼԜᴠͼⱨⱬᴠ᷅ͼⱨꞌꞌͼⱨⱬᴠԓͼᴟᴒⱲԜᴟᴑꞌᴒᴠᴠͼꜝⱱͼᴠᴒᴟ꞉ꜝᴢᴠꜜᴒᴠᴠԓͼ
ᴠᴒᴣᴒᴟ꞉ᴡᴦԓͼꜝᴟͼᴐԜᴢᴠԜꞌͼᴟᴒꞌԜᴡ꞉ꜝꜜᴠⱳ꞉ꜞͼᴡꜝͼⱷꜚ͟ԓͼᴤ꞉ꞌꞌͼԝᴒͼᴟᴒᴐꜝᴟᴑᴒᴑͼꜝꜜͼᴡⱳᴒͼⱨⱬͼꜞԜⱲᴒͼꜝⱱͼᴡⱳᴒͼᴒⱪϸⱴ᷅ͼⱨꜜᴦͼ
ⱨⱬͼᴟᴒꜞꜝᴟᴡᴒᴑͼᴡꜝͼᴡⱳᴒͼᴠ꞉ᴡᴒͼꜛᴒᴒᴡ꞉ꜜⱲͼᴐᴟ꞉ᴡᴒᴟ꞉ԜͼⱱꜝᴟͼԜͼᴠᴒᴟ꞉ꜝᴢᴠͼԜᴑᴣᴒᴟᴠᴒͼᴒᴣᴒꜜᴡͼꜛᴢᴠᴡͼԝᴒͼᴟᴒꜞꜝᴟᴡᴒᴑͼᴡꜝͼᴡⱳᴒͼ
ᴀꜞꜝꜜᴠꜝᴟͼᴢᴠ꞉ꜜⱲͼᴡⱳᴒͼᴀⱨⱬͼϸᴒꜞꜝᴟᴡ꞉ꜜⱲͼⱴꜝᴟꜛͼ꞉ꜜͼᴡⱳᴒͼⱬⱫⱪͼᴠᴦᴠᴡᴒꜛᴤ꞉ᴡⱳ꞉ꜜͼ᷉᷾ͼⱳꜝᴢᴟᴠꜝⱱͼԝᴒᴐꜝꜛ꞉ꜜⱲͼ
ԜᴤԜᴟᴒͼꜝⱱͼᴡⱳᴒͼᴒᴣᴒꜜᴡ᷅ͼⱴꜝᴟͼԜꞌꞌͼᴠᴒᴟ꞉ꜝᴢᴠͼԜᴑᴣᴒᴟᴠᴒͼᴒᴣᴒꜜᴡᴠͼᴡⱳԜᴡͼԜᴟᴒͼᴟᴒꜞꜝᴟᴡᴒᴑͼԜᴠͼⱶⱨⱬͼԜᴡᴡԜᴐꞋᴠԓͼᴡⱳᴒͼ
͟ᴟ꞉ꜜᴐ꞉ꜞԜꞌͼⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟͼꜝᴟͼꜞⱳᴦᴠ꞉ᴐ꞉Ԝꜜͼᴑᴒᴠ꞉Ⱳꜜᴒᴒͼᴤ꞉ꞌꞌͼᴟᴒᴣ꞉ᴒᴤͼᴡⱳᴒͼᴒᴣᴒꜜᴡͼᴤ꞉ᴡⱳ꞉ꜜͼ᷉᷾ⱳꜝᴢᴟᴠͼꜝⱱͼ꞉ꜜ꞉ᴡ꞉Ԝꞌͼ
ꜜꜝᴡ꞉ⱱ꞉ᴐԜᴡ꞉ꜝꜜͼԜꜜᴑԓͼ꞉ꜜͼԜᴐᴐꜝᴟᴑԜꜜᴐᴒͼᴤ꞉ᴡⱳͼⱶⱨⱨϸ͟ԓͼᴒᴣԜꞌᴢԜᴡᴒͼ꞉ⱱͼ꞉ᴡͼᴟᴒꜞᴟᴒᴠᴒꜜᴡᴒᴑͼԜͼᴐꜝꜜⱱ꞉ᴟꜛᴒᴑͼⱶⱨⱬͼ
ԜᴡᴡԜᴐꞋ᷅ͼⱴꜝᴟͼԜꞌꞌͼꜜꜝꜜ᷄ᴠᴒᴟ꞉ꜝᴢᴠͼⱨⱬᴠͼᴡⱳԜᴡͼԜᴟᴒͼᴟᴒꜞꜝᴟᴡᴒᴑͼԜᴠͼⱶⱨⱬͼԜᴡᴡԜᴐꞋᴠԓͼᴡⱳᴒͼ͟ᴟ꞉ꜜᴐ꞉ꜞԜꞌͼⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟͼꜝᴟͼ
ꜞⱳᴦᴠ꞉ᴐ꞉Ԝꜜͼᴑᴒᴠ꞉Ⱳꜜᴒᴒͼᴤ꞉ꞌꞌͼᴟᴒᴣ꞉ᴒᴤͼᴡⱳᴒͼᴒᴣᴒꜜᴡͼᴤ꞉ᴡⱳ꞉ꜜͼ᷊ͼᴑԜᴦᴠͼꜝⱱͼ꞉ꜜ꞉ᴡ꞉Ԝꞌꜜꜝᴡ꞉ⱱ꞉ᴐԜᴡ꞉ꜝꜜͼԜꜜᴑԓͼ꞉ꜜͼ
ԜᴐᴐꜝᴟᴑԜꜜᴐᴒͼᴤ꞉ᴡⱳͼⱶⱨⱨϸ͟ԓͼᴒᴣԜꞌᴢԜᴡᴒͼ꞉ⱱͼ꞉ᴡͼᴟᴒꜞᴟᴒᴠᴒꜜᴡᴒᴑͼԜͼᴐꜝꜜⱱ꞉ᴟꜛᴒᴑͼⱶⱨⱬͼԜᴡᴡԜᴐꞋ᷅ͼⱷⱱͼꜜᴒᴐᴒᴠᴠԜᴟᴦͼⱱꜝᴟͼ
ᴡⱳᴒͼᴒᴣԜꞌᴢԜᴡ꞉ꜝꜜԓͼᴡⱳᴒͼⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟͼꜝᴟͼᴑᴒᴠ꞉ⱲꜜᴒᴒͼꜛԜᴦͼᴐꜝꜜᴡԜᴐᴡͼᴡⱳᴒͼᴠᴢԝ꞊ᴒᴐᴡͼⱱꜝᴟͼԜᴑᴑ꞉ᴡ꞉ꜝꜜԜꞌͼ
꞉ꜜⱱꜝᴟꜛԜᴡ꞉ꜝꜜ᷅ͼⱨꜜᴦͼᴠᴢԝ꞊ᴒᴐᴡ᷄ᴟᴒꜞꜝᴟᴡᴒᴑͼԜᴡᴡԜᴐꞋͼꜜꜝᴡͼᴐꜝꜜⱱ꞉ᴟꜛᴒᴑͼԝᴦͼᴡⱳᴒͼⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟͼꜛᴢᴠᴡͼⱳԜᴣᴒͼԜꜜͼ
ԜꞌᴡᴒᴟꜜԜᴡᴒͼⱨⱬͼᴑ꞉ԜⱲꜜꜝᴠ꞉ᴠͼᴟᴒᴐꜝᴟᴑᴒᴑ᷅ͼⱨꞌꞌͼᴠᴢԝ꞊ᴒᴐᴡ᷄ᴟᴒꜞꜝᴟᴡᴒᴑͼԜꜜᴑͼⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟ᷄ᴐꜝꜜⱱ꞉ᴟꜛᴒᴑͼⱶⱨⱬͼ
ԜᴡᴡԜᴐꞋᴠͼᴤ꞉ꞌꞌͼԝᴒͼᴟᴒᴐꜝᴟᴑᴒᴑͼ꞉ꜜͼᴡⱳᴒͼᴒⱪϸⱴ᷅
ⱬꜛᴒᴟⱲᴒꜜᴐᴦͼᴑᴒꜞԜᴟᴡꜛᴒꜜᴡͼᴣ꞉ᴠ꞉ᴡᴠͼⱱꜝᴟͼⱶⱨⱬͼԜᴡᴡԜᴐꞋᴠͼԜꜜᴑͼⱶⱨⱬͼԜᴡᴡԜᴐꞋᴠͼᴟᴒᴠᴢꞌᴡ꞉ꜜⱲͼ꞉ꜜͼⱳꜝᴠꜞ꞉ᴡԜꞌͼ
Ԝᴑꜛ꞉ᴠᴠ꞉ꜝꜜᴠͼᴤ꞉ꞌꞌͼԝᴒͼᴐԜꜞᴡᴢᴟᴒᴑ᷅
ᴁꜝͼԝᴒͼᴐꜝꜜⱱ꞉ᴟꜛᴒᴑͼԜᴠͼԜꜜͼⱶⱨⱬͼԜᴡᴡԜᴐꞋԓͼᴡⱳᴒͼᴒᴣᴒꜜᴡͼꜛᴢᴠᴡͼⱳԜᴣᴒͼᴠᴦꜛꜞᴡꜝꜛᴠͼꜝᴟͼᴠ꞉Ⱳꜜᴠͼᴐꜝꜜᴠ꞉ᴠᴡᴒꜜᴡͼᴤ꞉ᴡⱳͼ
ԜꜜͼԜᴡᴡԜᴐꞋͼ꞉ꜜͼԜᴡͼꞌᴒԜᴠᴡͼꜝꜜᴒͼꜝⱱͼᴡⱳᴒͼⱱꜝꞌꞌꜝᴤ꞉ꜜⱲͼꞌꜝᴐԜᴡ꞉ꜝꜜᴠⱡͼ
ᶄ
͟ᴒᴟ꞉ꜞⱳᴒᴟԜꞌͼԜꜜⱲ꞉ꜝᴒᴑᴒꜛԜⱡͼᴐᴢᴡԜꜜᴒꜝᴢᴠͼᴠᴤᴒꞌꞌ꞉ꜜⱲͼ꞉ꜜᴣꜝꞌᴣ꞉ꜜⱲͼԜꜜͼᴒᴥᴡᴟᴒꜛ꞉ᴡᴦԓͼᴡⱳᴒͼⱱԜᴐᴒԓͼꜜᴒᴐꞋԓͼᴡꜝᴟᴠꜝԓͼ
Ԝꜜᴑ᷆ꜝᴟͼⱲᴒꜜ꞉ᴡꜝᴢᴟ꞉ꜜԜᴟᴦͼᴟᴒⱲ꞉ꜝꜜ
ᶄ
ⱨԝᴑꜝꜛ꞉ꜜԜꞌͼԜꜜⱲ꞉ꜝᴒᴑᴒꜛԜⱡͼԜԝᴑꜝꜛ꞉ꜜԜꞌͼꜞԜ꞉ꜜԓͼᴤ꞉ᴡⱳͼꜝᴟͼᴤ꞉ᴡⱳꜝᴢᴡͼԜԝᴑꜝꜛ꞉ꜜԜꞌͼᴑ꞉ᴠᴡᴒꜜᴡ꞉ꜝꜜԓͼꜜԜᴢᴠᴒԜԓͼ
ᴣꜝꜛ꞉ᴡ꞉ꜜⱲԓͼꜝᴟͼᴑ꞉ԜᴟᴟⱳᴒԜ
ᶄ
ꜙԜᴟᴦꜜⱲᴒԜꞌͼԜꜜⱲ꞉ꜝᴒᴑᴒꜛԜⱡͼᴠᴡᴟ꞉ᴑꜝᴟԓͼᴑᴦᴠꜞꜜᴒԜԓͼᴑ꞉ⱱⱱ꞉ᴐᴢꞌᴡᴦͼᴠꜞᴒԜꞋ꞉ꜜⱲԓͼᴑ꞉ⱱⱱ꞉ᴐᴢꞌᴡᴦͼᴠᴤԜꞌꞌꜝᴤ꞉ꜜⱲԓͼᴡⱳᴟꜝԜᴡͼ
ᴡ꞉Ⱳⱳᴡᴒꜜ꞉ꜜⱲԓͼꜝᴟͼᴠᴤᴒꞌꞌ꞉ꜜⱲͼꜝⱱͼᴡⱳᴒͼᴡꜝꜜⱲᴢᴒԓͼꜞԜꞌԜᴡᴒԓͼᴢᴣᴢꞌԜԓͼꜝᴟͼꞌԜᴟᴦꜜᴥ
Ⱬᴒᴠꜞ꞉ᴡᴒͼᴡⱳᴒͼꜞᴟᴒᴠᴒꜜᴐᴒͼꜝⱱͼᴡⱳᴒᴠᴒͼᴠᴦꜛꜞᴡꜝꜛᴠԓͼᴡⱳᴒͼⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟͼꜛԜᴦͼᴠᴡ꞉ꞌꞌͼᴐꞌ꞉ꜜ꞉ᴐԜꞌꞌᴦͼᴑᴒᴡᴒᴟꜛ꞉ꜜᴒͼᴡⱳԜᴡͼ
ᴡⱳᴒͼᴒᴣᴒꜜᴡͼᴑ꞉ᴑͼꜜꜝᴡͼᴟᴒꜞᴟᴒᴠᴒꜜᴡͼԜꜜͼⱶⱨⱬͼԜᴡᴡԜᴐꞋͼ꞉ⱱͼᴡⱳᴒᴟᴒͼԜᴟᴒͼⱱᴒԜᴡᴢᴟᴒᴠͼᴡⱳԜᴡͼᴠᴡᴟꜝꜜⱲꞌᴦͼᴟᴒⱱᴢᴡᴒͼᴠᴢᴐⱳͼԜͼ
ᴑ꞉ԜⱲꜜꜝᴠ꞉ᴠ᷅ͼⱴꜝᴟͼᴒᴥԜꜛꜞꞌᴒԓͼᴡⱳᴒͼᴟᴒꜞꜝᴟᴡᴒᴑͼᴒᴣᴒꜜᴡͼ꞉ᴠͼԜᴐᴐꜝꜛꜞԜꜜ꞉ᴒᴑͼԝᴦͼᴠᴦꜛꜞᴡꜝꜛᴠͼᴡⱳԜᴡͼԜᴟᴒͼꜜꜝᴡͼ
ᴐꜝꜜᴠ꞉ᴠᴡᴒꜜᴡͼᴤ꞉ᴡⱳͼԜꜜͼⱶⱨⱬͼԜᴡᴡԜᴐꞋͼӿᴒ᷅Ⱳ᷅ԓͼᴢᴟᴡ꞉ᴐԜᴟ꞉ԜԐԓͼᴡⱳᴒͼᴟᴒꜞꜝᴟᴡᴒᴑͼᴒᴣᴒꜜᴡͼꜞᴒᴟᴠ꞉ᴠᴡᴠͼᴤᴒꞌꞌͼԝᴒᴦꜝꜜᴑͼᴡⱳᴒͼ
ᴡᴦꜞ꞉ᴐԜꞌͼᴡ꞉ꜛᴒͼᴐꜝᴢᴟᴠᴒͼꜝⱱͼԜꜜͼⱶⱨⱬͼԜᴡᴡԜᴐꞋԓͼꜝᴟᴡⱳᴒᴟᴒͼ꞉ᴠͼԜͼꞌ꞉ꞋᴒꞌᴦͼԜꞌᴡᴒᴟꜜԜᴡᴒͼᴒᴡ꞉ꜝꞌꜝⱲᴦͼⱱꜝᴟͼᴡⱳᴒͼᴒᴣᴒꜜᴡͼӿᴒ᷅Ⱳ᷅ԓͼ
ᴡⱳᴒͼᴠᴢԝ꞊ᴒᴐᴡᶳᴠͼԜԝᴑꜝꜛ꞉ꜜԜꞌͼᴠᴦꜛꜞᴡꜝꜛᴠͼԜᴟᴒԜᴡᴡᴟ꞉ԝᴢᴡԜԝꞌᴒͼᴡꜝͼԜͼᴣ꞉ᴟԜꞌͼⱲԜᴠᴡᴟꜝᴒꜜᴡᴒᴟ꞉ᴡ꞉ᴠͼꜝᴢᴡԝᴟᴒԜꞋͼ꞉ꜜͼᴡⱳᴒͼ
ⱳꜝᴢᴠᴒⱳꜝꞌᴑԐ᷅ͼ
ᴁꜝͼԝᴒͼᴐꜝᴢꜜᴡᴒᴑͼԜᴠͼԜͼᴢꜜ꞉ꜟᴢᴒͼԜᴡᴡԜᴐꞋͼᴑ꞉ᴠᴡ꞉ꜜᴐᴡͼⱱᴟꜝꜛͼᴡⱳᴒͼꜞᴟᴒᴣ꞉ꜝᴢᴠͼԜᴡᴡԜᴐꞋԓͼᴡⱳᴒͼꜜᴒᴤͼᴠᴦꜛꜞᴡꜝꜛᴠͼꜛᴢᴠᴡͼ
ꜝᴐᴐᴢᴟͼԜᴡͼꞌᴒԜᴠᴡͼ᷉᷾ͼⱳꜝᴢᴟᴠͼԜⱱᴡᴒᴟͼᴟᴒᴠꜝꞌᴢᴡ꞉ꜝꜜͼꜝⱱͼᴡⱳᴒͼꜞᴟ꞉ꜝᴟͼԜᴡᴡԜᴐꞋᶳᴠͼᴠᴦꜛꜞᴡꜝꜛᴠ᷅
Interim Analysis and Data Safety Monitoring Board:
꜠ꜝͼ꞉ꜜᴡᴒᴟ꞉ꜛͼԜꜜԜꞌᴦᴠ꞉ᴠͼ꞉ᴠͼꜞꞌԜꜜꜜᴒᴑͼⱱꜝᴟͼᴡⱳ꞉ᴠͼᴠᴡᴢᴑᴦ᷅ͼⱫᴢᴟ꞉ꜜⱲͼᴡⱳᴒͼᴠᴡᴢᴑᴦԓͼꜞԜᴡ꞉ᴒꜜᴡͼᴠԜⱱᴒᴡᴦͼᴤ꞉ꞌꞌͼԝᴒͼ
ꜛꜝꜜ꞉ᴡꜝᴟᴒᴑͼꜝꜜͼԜͼᴐꜝꜜᴡ꞉ꜜᴢꜝᴢᴠͼԝԜᴠ꞉ᴠͼԝᴦͼᴡⱳᴒͼꜚᴒᴑ꞉ᴐԜꞌͼꜚꜝꜜ꞉ᴡꜝᴟͼᴢꜜᴡ꞉ꞌͼᴡⱳᴒͼꞌԜᴠᴡͼꜞԜᴡ꞉ᴒꜜᴡͼᴐꜝꜛꜞꞌᴒᴡᴒᴠͼⱳ꞉ᴠͼ
ꜝᴟͼⱳᴒᴟͼꞌԜᴠᴡͼᴠᴐⱳᴒᴑᴢꞌᴒᴑͼᴠᴡᴢᴑᴦͼԜᴠᴠᴒᴠᴠꜛᴒꜜᴡ᷅ͼ

Ⱬᴅ᷄᷉Ⱡ᷊᷇
ⱪꞌ꞉ꜜ꞉ᴐԜꞌͼᴁᴟ꞉Ԝꞌͼ͟ᴟꜝᴡꜝᴐꜝꞌⱡͼⱫᴅ᷄᷉Ⱡ᷊᷊᷇᷄᷇
ⱨꜛᴒꜜᴑꜛᴒꜜᴡͼ᷊᷅᷇ⱴ꞉ꜜԜꞌⱡͼ᷇ⱠͼꜗԜꜜᴢԜᴟᴦ᷉᷇᷈ⅎ
ⱪꜝꜜⱱ꞉ᴑᴒꜜᴡ꞉Ԝꞌ
͟ԜⱲᴒͼ᷈᷾
ⱫᴦԜᴥͼⱪꜝᴟꜞ᷅
ⱨꜜͼ꞉ꜜᴑᴒꜞᴒꜜᴑᴒꜜᴡͼⱫԜᴡԜͼᴀԜⱱᴒᴡᴦͼꜚꜝꜜ꞉ᴡꜝᴟ꞉ꜜⱲͼⱩꜝԜᴟᴑͼӿⱫᴀꜚⱩԐͼᴤ꞉ꞌꞌͼԜꞌᴠꜝͼԝᴒͼᴒᴠᴡԜԝꞌ꞉ᴠⱳᴒᴑͼᴡꜝͼꜞᴟꜝᴣ꞉ᴑᴒͼ
ԜꜜͼꜝꜜⱲꜝ꞉ꜜⱲԓͼ꞉ꜜᴑᴒꜞᴒꜜᴑᴒꜜᴡͼᴟᴒᴣ꞉ᴒᴤͼԜꜜᴑͼԜᴠᴠᴒᴠᴠꜛᴒꜜᴡͼꜝⱱͼᴡⱳᴒͼᴠԜⱱᴒᴡᴦͼᴑԜᴡԜԓͼԜꜜᴑͼᴡꜝͼᴠԜⱱᴒⱲᴢԜᴟᴑͼᴡⱳᴒͼ
꞉ꜜᴡᴒᴟᴒᴠᴡᴠͼԜꜜᴑͼᴠԜⱱᴒᴡᴦͼꜝⱱͼᴡⱳᴒͼꜞԜᴟᴡ꞉ᴐ꞉ꜞԜᴡ꞉ꜜⱲͼꜞԜᴡ꞉ᴒꜜᴡᴠͼ꞉ꜜͼᴡⱳᴒͼᴠᴡᴢᴑᴦ᷅ͼᴁⱳᴒͼꜝꜜⱲꜝ꞉ꜜⱲͼᴟᴒᴣ꞉ᴒᴤͼꜝⱱͼᴀⱨⱬᴠͼ
Ԝꜜᴑͼꜝᴡⱳᴒᴟͼᴟᴒᴠꜞꜝꜜᴠ꞉ԝ꞉ꞌ꞉ᴡ꞉ᴒᴠͼꜝⱱͼᴡⱳᴒͼⱫᴀꜚⱩͼԜᴟᴒͼᴑᴒᴠᴐᴟ꞉ԝᴒᴑͼ꞉ꜜͼᴡⱳᴒͼⱫᴀꜚⱩͼⱪⱳԜᴟᴡᴒᴟ᷅
Individual Stopping Rules:
Ⱬꜝᴠ꞉ꜜⱲͼⱱꜝᴟͼԜꜜᴦͼ꞉ꜜᴑ꞉ᴣ꞉ᴑᴢԜꞌͼᴠᴢԝ꞊ᴒᴐᴡͼᴤ꞉ꞌꞌͼԝᴒͼᴑ꞉ᴠᴐꜝꜜᴡ꞉ꜜᴢᴒᴑͼ꞉ⱱͼᴡⱳᴒͼᴠᴢԝ꞊ᴒᴐᴡͼᴒᴥꜞᴒᴟ꞉ᴒꜜᴐᴒᴠͼԜͼ
Ⱬᴅ᷄᷉Ⱡ᷊᷇᷄ᴟᴒꞌԜᴡᴒᴑͼᴀⱨⱬͼӿꜝᴟͼԜͼⱫᴅ᷄᷉Ⱡ᷊᷇᷄ᴟᴒꞌԜᴡᴒᴑԓͼᴐꞌ꞉ꜜ꞉ᴐԜꞌꞌᴦͼᴠ꞉Ⱳꜜ꞉ⱱ꞉ᴐԜꜜᴡꜜꜝꜜ᷄ᴠᴒᴟ꞉ꜝᴢᴠͼⱨⱬԐͼᴡⱳԜᴡԓͼ꞉ꜜͼ
ᴡⱳᴒͼԜᴠᴠᴒᴠᴠꜛᴒꜜᴡͼꜝⱱͼᴡⱳᴒͼⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟͼᴤԜᴟᴟԜꜜᴡᴠͼᴑ꞉ᴠᴐꜝꜜᴡ꞉ꜜᴢԜᴡ꞉ꜝꜜͼⱱᴟꜝꜛͼⱱᴢᴟᴡⱳᴒᴟͼᴑꜝᴠ꞉ꜜⱲͼⱱꜝᴟͼᴡⱳԜᴡͼ
ᴠᴢԝ꞊ᴒᴐᴡᶳᴠͼᴤᴒꞌꞌ᷄ԝᴒ꞉ꜜⱲ᷅ͼᴁⱳᴒͼⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟͼⱳԜᴠͼᴡⱳᴒͼԜԝ꞉ꞌ꞉ᴡᴦͼᴡꜝͼᴐꜝꜜᴡԜᴐᴡͼԜꜜᴑͼᴐꜝꜜᴠᴢꞌᴡͼᴤ꞉ᴡⱳͼᴡⱳᴒͼꜚᴒᴑ꞉ᴐԜꞌͼ
ꜚꜝꜜ꞉ᴡꜝᴟͼꜝꜜͼᴠᴢᴐⱳͼꜛԜᴡᴡᴒᴟᴠ᷅ͼᴀᴢԝ꞊ᴒᴐᴡᴠͼᴤ꞉ꞌꞌͼᴐꜝꜜᴡ꞉ꜜᴢᴒͼᴡꜝͼԝᴒͼⱱꜝꞌꞌꜝᴤᴒᴑͼᴡⱳᴟꜝᴢⱲⱳͼᴐꜝꜛꜞꞌᴒᴡ꞉ꜝꜜͼꜝⱱͼԜꞌꞌͼ
ᴠᴐⱳᴒᴑᴢꞌᴒᴑͼᴣ꞉ᴠ꞉ᴡᴠԓͼᴢꜜꞌᴒᴠᴠͼᴡⱳᴒᴦͼᴟᴒꜟᴢᴒᴠᴡͼᴡꜝͼԝᴒͼᴑ꞉ᴠᴐꜝꜜᴡ꞉ꜜᴢᴒᴑͼⱱᴟꜝꜛͼᴡⱳᴒͼᴠᴡᴢᴑᴦ᷅ͼᴀᴢԝ꞊ᴒᴐᴡᴠͼᴤⱳꜝͼԜᴟᴒͼ
ᴑ꞉ᴠᴐꜝꜜᴡ꞉ꜜᴢᴒᴑͼⱱᴟꜝꜛͼⱱᴢᴟᴡⱳᴒᴟͼᴑꜝᴠ꞉ꜜⱲͼᴤ꞉ꞌꞌͼꜜꜝᴡͼԝᴒͼᴒꞌ꞉Ⱳ꞉ԝꞌᴒͼᴡꜝͼꜞԜᴟᴡ꞉ᴐ꞉ꜞԜᴡᴒͼ꞉ꜜͼᴡⱳᴒͼ꜡ꜙⱬ᷅

Ⱬᴅ᷄᷉Ⱡ᷊᷇
ⱪꞌ꞉ꜜ꞉ᴐԜꞌͼᴁᴟ꞉Ԝꞌͼ͟ᴟꜝᴡꜝᴐꜝꞌⱡͼⱫᴅ᷄᷉Ⱡ᷊᷊᷇᷄᷇
ⱨꜛᴒꜜᴑꜛᴒꜜᴡͼ᷊᷅᷇ⱴ꞉ꜜԜꞌⱡͼ᷇ⱠͼꜗԜꜜᴢԜᴟᴦ᷉᷇᷈ⅎ
ⱪꜝꜜⱱ꞉ᴑᴒꜜᴡ꞉Ԝꞌ
͟ԜⱲᴒͼ᷿᷈
ⱫᴦԜᴥͼⱪꜝᴟꜞ᷅
Criteria for Evaluation:
͟ᴟ꞉ꜛԜᴟᴦͼԜꜜᴑͼᴠᴒᴐꜝꜜᴑԜᴟᴦͼᴒⱱⱱ꞉ᴐԜᴐᴦͼᴒꜜᴑꜞꜝ꞉ꜜᴡᴠͼᴤ꞉ꞌꞌͼԝᴒͼԝԜᴠᴒᴑͼꜝꜜͼԜꜜͼᴒⱱⱱ꞉ᴐԜᴐᴦͼᴒᴣԜꞌᴢԜᴡ꞉ꜝꜜͼꜞᴒᴟ꞉ꜝᴑͼ
ᴠꜞԜꜜꜜ꞉ꜜⱲͼⱫԜᴦͼ᷇ͼӿԜⱱᴡᴒᴟͼᴠᴡᴢᴑᴦͼᴑᴟᴢⱲͼԜᴑꜛ꞉ꜜ꞉ᴠᴡᴟԜᴡ꞉ꜝꜜԐͼᴡⱳᴟꜝᴢⱲⱳͼⱫԜᴦͼ᷈˲᷉ԓ ᴢꜜꞌᴒᴠᴠͼꜝᴡⱳᴒᴟᴤ꞉ᴠᴒͼ
ᴠꜞᴒᴐ꞉ⱱ꞉ᴒᴑ᷅
Primary Efficacy Endpoint

꜠ᴢꜛԝᴒᴟͼꜝⱱͼⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟ᷄ᴐꜝꜜⱱ꞉ᴟꜛᴒᴑͼⱶⱨⱬͼԜᴡᴡԜᴐꞋᴠͼᴑᴢᴟ꞉ꜜⱲͼᴡⱳᴒͼᴒⱱⱱ꞉ᴐԜᴐᴦͼᴒᴣԜꞌᴢԜᴡ꞉ꜝꜜͼꜞᴒᴟ꞉ꜝᴑͼ
ӿⱫԜᴦͼ᷇ͼᴡⱳᴟꜝᴢⱲⱳͼⱫԜᴦͼ᷈˲᷉Ԑ
Secondary Efficacy Endpoints (rank ordered)
᷈᷅꜠ᴢꜛԝᴒᴟͼꜝⱱͼⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟ᷄ᴐꜝꜜⱱ꞉ᴟꜛᴒᴑͼⱶⱨⱬͼԜᴡᴡԜᴐꞋᴠͼᴟᴒꜟᴢ꞉ᴟ꞉ꜜⱲͼԜᴐᴢᴡᴒͼᴡᴟᴒԜᴡꜛᴒꜜᴡͼᴑᴢᴟ꞉ꜜⱲͼᴡⱳᴒͼ
ᴒⱱⱱ꞉ᴐԜᴐᴦͼᴒᴣԜꞌᴢԜᴡ꞉ꜝꜜͼꜞᴒᴟ꞉ꜝᴑͼӿⱫԜᴦͼ᷇ͼᴡⱳᴟꜝᴢⱲⱳͼⱫԜᴦͼ᷈˲᷉Ԑ
᷉᷅꜠ᴢꜛԝᴒᴟͼꜝⱱͼꜛꜝᴑᴒᴟԜᴡᴒͼꜝᴟͼᴠᴒᴣᴒᴟᴒͼⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟ᷄ᴐꜝꜜⱱ꞉ᴟꜛᴒᴑͼⱶⱨⱬͼԜᴡᴡԜᴐꞋᴠͼᴑᴢᴟ꞉ꜜⱲͼᴡⱳᴒͼᴒⱱⱱ꞉ᴐԜᴐᴦͼ
ᴒᴣԜꞌᴢԜᴡ꞉ꜝꜜͼꜞᴒᴟ꞉ꜝᴑͼӿⱫԜᴦͼ᷇ͼᴡⱳᴟꜝᴢⱲⱳͼⱫԜᴦͼ᷈˲᷉Ԑ
᷊᷅꜠ᴢꜛԝᴒᴟͼꜝⱱͼⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟ᷄ᴐꜝꜜⱱ꞉ᴟꜛᴒᴑͼⱶⱨⱬͼԜᴡᴡԜᴐꞋᴠͼꜝᴐᴐᴢᴟᴟ꞉ꜜⱲͼꜝꜜͼⱫԜᴦͼ᷈᷾ͼԜⱱᴡᴒᴟͼԜᴑꜛ꞉ꜜ꞉ᴠᴡᴟԜᴡ꞉ꜝꜜͼ
ꜝⱱͼᴠᴡᴢᴑᴦͼᴑᴟᴢⱲͼᴡⱳᴟꜝᴢⱲⱳͼⱫԜᴦͼ᷈˲᷉ͼӿⱫԜᴦͼ᷈᷾ͼᴡⱳᴟꜝᴢⱲⱳͼⱫԜᴦͼ᷈˲᷉Ԑ
Exploratory Efficacy Endpoints

ᴁ꞉ꜛᴒͼᴡꜝͼⱱ꞉ᴟᴠᴡͼⱶⱨⱬͼԜᴡᴡԜᴐꞋͼԜⱱᴡᴒᴟͼⱫԜᴦͼ᷈᷾ԓͼ꞉᷅ᴒ᷅ԓͼᴑᴢᴟԜᴡ꞉ꜝꜜͼᴡⱳԜᴡͼԜͼᴠᴢԝ꞊ᴒᴐᴡͼ꞉ᴠͼԜᴡᴡԜᴐꞋ᷄ⱱᴟᴒᴒͼԜⱱᴡᴒᴟͼⱫԜᴦͼ
᷈᷾ͼ

꜠ᴢꜛԝᴒᴟͼꜝⱱͼⱳ꞉Ⱳⱳ᷄ꜛꜝᴟԝ꞉ᴑ꞉ᴡᴦͼⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟ᷄ᴐꜝꜜⱱ꞉ᴟꜛᴒᴑͼⱶⱨⱬͼԜᴡᴡԜᴐꞋᴠͼᴑᴢᴟ꞉ꜜⱲͼᴡⱳᴒͼᴒⱱⱱ꞉ᴐԜᴐᴦͼ
ᴒᴣԜꞌᴢԜᴡ꞉ꜝꜜͼꜞᴒᴟ꞉ꜝᴑⱢͼԜͼⱳ꞉Ⱳⱳ᷄ꜛꜝᴟԝ꞉ᴑ꞉ᴡᴦͼⱶⱨⱬͼԜᴡᴡԜᴐꞋͼ꞉ᴠͼᴑᴒⱱ꞉ꜜᴒᴑͼԜᴠͼԜꜜᴦͼԜᴡᴡԜᴐꞋͼᴡⱳԜᴡͼⱳԜᴠͼԜᴡͼꞌᴒԜᴠᴡͼ
ꜝꜜᴒͼꜝⱱͼᴡⱳᴒͼⱱꜝꞌꞌꜝᴤ꞉ꜜⱲͼᴐⱳԜᴟԜᴐᴡᴒᴟ꞉ᴠᴡ꞉ᴐᴠⱡͼᴠᴒᴣᴒᴟᴒԓͼᴟᴒᴠᴢꞌᴡᴠͼ꞉ꜜͼⱳꜝᴠꜞ꞉ᴡԜꞌ꞉ᴧԜᴡ꞉ꜝꜜͼӿᴒᴥᴐᴒꜞᴡͼ
ⱳꜝᴠꜞ꞉ᴡԜꞌ꞉ᴧԜᴡ꞉ꜝꜜͼⱱꜝᴟͼꜝԝᴠᴒᴟᴣԜᴡ꞉ꜝꜜͼⱣͼ᷉᷾ͼⱳꜝᴢᴟᴠԐԓͼⱳᴒꜛꜝᴑᴦꜜԜꜛ꞉ᴐԜꞌꞌᴦͼᴠ꞉Ⱳꜜ꞉ⱱ꞉ᴐԜꜜᴡͼӿᴠᴦᴠᴡꜝꞌ꞉ᴐͼԝꞌꜝꜝᴑͼ
ꜞᴟᴒᴠᴠᴢᴟᴒͼⱣͼⱠ᷇ԓͼᴟᴒꜟᴢ꞉ᴟᴒᴠͼⱷᴃͼⱳᴦᴑᴟԜᴡ꞉ꜝꜜԓͼꜝᴟͼԜᴠᴠꜝᴐ꞉Ԝᴡᴒᴑͼᴤ꞉ᴡⱳͼᴠᴦꜜᴐꜝꜞᴒͼꜝᴟͼꜜᴒԜᴟ᷄ᴠᴦꜜᴐꜝꜞᴒԐͼꜝᴟͼ
ꞌԜᴟᴦꜜⱲᴒԜꞌ᷅
Safety Measures:

ⱨᴑᴣᴒᴟᴠᴒͼᴒᴣᴒꜜᴡᴠͼӿⱨⱬᴠԐͼ꞉ꜜᴐꞌᴢᴑ꞉ꜜⱲͼᴠᴒᴟ꞉ꜝᴢᴠͼԜᴑᴣᴒᴟᴠᴒͼᴒᴣᴒꜜᴡᴠͼӿᴀⱨⱬᴠԐͼԜꜜᴑͼԜᴑᴣᴒᴟᴠᴒͼᴒᴣᴒꜜᴡᴠͼꜝⱱͼ
ᴠꜞᴒᴐ꞉Ԝꞌͼ꞉ꜜᴡᴒᴟᴒᴠᴡͼӿⱨⱬᴀⱷԐ

ⱪꞌ꞉ꜜ꞉ᴐԜꞌͼꞌԜԝꜝᴟԜᴡꜝᴟᴦͼᴡᴒᴠᴡ꞉ꜜⱲͼӿⱳᴒꜛԜᴡꜝꞌꜝⱲᴦԓͼᴐꞌ꞉ꜜ꞉ᴐԜꞌͼᴐⱳᴒꜛ꞉ᴠᴡᴟᴦԓͼᴐꜝԜⱲᴢꞌԜᴡ꞉ꜝꜜͼԜꜜᴑͼᴢᴟ꞉ꜜԜꞌᴦᴠ꞉ᴠԐ

ᴃ꞉ᴡԜꞌᴠͼᴠ꞉Ⱳꜜᴠͼ꞉ꜜᴐꞌᴢᴑ꞉ꜜⱲͼԝꞌꜝꜝᴑͼꜞᴟᴒᴠᴠᴢᴟᴒԓͼⱳᴒԜᴟᴡͼᴟԜᴡᴒԓͼԝꜝᴑᴦͼᴡᴒꜛꜞᴒᴟԜᴡᴢᴟᴒͼԜꜜᴑͼᴟᴒᴠꜞ꞉ᴟԜᴡꜝᴟᴦͼᴟԜᴡᴒ

͟ⱳᴦᴠ꞉ᴐԜꞌͼᴒᴥԜꜛ꞉ꜜԜᴡ꞉ꜝꜜ

᷈᷉᷄ꞌᴒԜᴑͼᴒꞌᴒᴐᴡᴟꜝᴐԜᴟᴑ꞉ꜝⱲᴟԜꜛͼӿⱬⱪⱵԐ
Additional Measures:

͟ⱳԜᴟꜛԜᴐꜝᴑᴦꜜԜꜛ꞉ᴐͼӿ͟ⱫԐͼᴒⱱⱱᴒᴐᴡᴠ

ⱨꜜᴡ꞉᷄ᴑᴟᴢⱲͼԜꜜᴡ꞉ԝꜝᴑᴦͼᴑᴒᴣᴒꞌꜝꜞꜛᴒꜜᴡ

͟ⱳԜᴟꜛԜᴐꜝꞋ꞉ꜜᴒᴡ꞉ᴐᴠͼӿ͟ꜘԐͼ

ⱶᴒԜꞌᴡⱳ᷄ᴟᴒꞌԜᴡᴒᴑͼꜟᴢԜꞌ꞉ᴡᴦͼꜝⱱͼꞌ꞉ⱱᴒͼԜᴠᴠᴒᴠᴠꜛᴒꜜᴡᴠ
Analysis Populations:
Intent-to-treat (ITT) Population: ᴤ꞉ꞌꞌͼ꞉ꜜᴐꞌᴢᴑᴒͼԜꞌꞌͼᴟԜꜜᴑꜝꜛ꞉ᴧᴒᴑͼᴠᴢԝ꞊ᴒᴐᴡᴠͼᴤⱳꜝͼԜᴟᴒͼ

Ⱬᴅ᷄᷉Ⱡ᷊᷇
ⱪꞌ꞉ꜜ꞉ᴐԜꞌͼᴁᴟ꞉Ԝꞌͼ͟ᴟꜝᴡꜝᴐꜝꞌⱡͼⱫᴅ᷄᷉Ⱡ᷊᷊᷇᷄᷇
ⱨꜛᴒꜜᴑꜛᴒꜜᴡͼ᷊᷅᷇ⱴ꞉ꜜԜꞌⱡͼ᷇ⱠͼꜗԜꜜᴢԜᴟᴦ᷉᷇᷈ⅎ
ⱪꜝꜜⱱ꞉ᴑᴒꜜᴡ꞉Ԝꞌ
͟ԜⱲᴒͼ᷈⅍
ⱫᴦԜᴥͼⱪꜝᴟꜞ᷅
Ԝᴑꜛ꞉ꜜ꞉ᴠᴡᴒᴟᴒᴑͼԜᴡͼꞌᴒԜᴠᴡͼ᷈ͼᴑꜝᴠᴒͼꜝⱱͼԜᴐᴡ꞉ᴣᴒͼⱷꜚ͟ͼꜝᴟͼꜞꞌԜᴐᴒԝꜝ᷅ͼᴁⱳᴒͼꜞᴟ꞉ꜛԜᴟᴦͼᴒⱱⱱ꞉ᴐԜᴐᴦͼԜꜜԜꞌᴦᴠᴒᴠͼᴤ꞉ꞌꞌͼԝᴒͼ
ᴐԜᴟᴟ꞉ᴒᴑͼꜝᴢᴡͼᴤ꞉ᴡⱳͼᴡⱳᴒͼⱷᴁᴁͼ͟ꜝꜞᴢꞌԜᴡ꞉ꜝꜜ᷅
Safety Population: ᴤ꞉ꞌꞌͼ꞉ꜜᴐꞌᴢᴑᴒͼԜꞌꞌͼᴠᴢԝ꞊ᴒᴐᴡᴠͼᴤⱳꜝͼԜᴟᴒͼԜᴑꜛ꞉ꜜ꞉ᴠᴡᴒᴟᴒᴑͼԜᴡͼꞌᴒԜᴠᴡͼ᷈ͼᴑꜝᴠᴒͼꜝⱱͼԜᴐᴡ꞉ᴣᴒͼ
ⱷꜚ͟ͼꜝᴟͼꜞꞌԜᴐᴒԝꜝ᷅ⱨꞌꞌᴠԜⱱᴒᴡᴦԜꜜԜꞌᴦᴠᴒᴠᴤ꞉ꞌꞌᴢᴠᴒᴡⱳᴒᴀԜⱱᴒᴡᴦ͟ꜝꜞᴢꞌԜᴡ꞉ꜝꜜ᷅
Sample Size Determination:
͟ꜝᴤᴒᴟͼԜꜜԜꞌᴦᴠ꞉ᴠͼԜꜜᴑͼᴠԜꜛꜞꞌᴒͼᴠ꞉ᴧᴒͼᴒᴠᴡ꞉ꜛԜᴡ꞉ꜝꜜͼᴤԜᴠͼԝԜᴠᴒᴑͼꜝꜜͼ᷈᷇᷇᷇ͼᴐꜝꜛꜞᴢᴡᴒᴟͼᴠ꞉ꜛᴢꞌԜᴡ꞉ꜝꜜᴠͼᴢᴠ꞉ꜜⱲͼԜͼ
ⱲᴒꜜᴒᴟԜꞌ꞉ᴧᴒᴑͼꞌ꞉ꜜᴒԜᴟͼꜛꜝᴑᴒꞌͼⱱꜝᴟᴐꜝᴢꜜᴡͼᴑԜᴡԜͼԜᴠᴠᴢꜛ꞉ꜜⱲͼԜͼ͟ꜝ꞉ᴠᴠꜝꜜͼᴑ꞉ᴠᴡᴟ꞉ԝᴢᴡ꞉ꜝꜜͼᴤ꞉ᴡⱳͼ͟ᴒԜᴟᴠꜝꜜͼᴐⱳ꞉᷄
ᴠꜟᴢԜᴟᴒͼᴠᴐԜꞌ꞉ꜜⱲͼꜝⱱͼᴠᴡԜꜜᴑԜᴟᴑͼᴒᴟᴟꜝᴟᴠͼᴡꜝͼԜᴐᴐꜝᴢꜜᴡͼⱱꜝᴟͼꜞꜝᴡᴒꜜᴡ꞉Ԝꞌͼꜝᴣᴒᴟᴑ꞉ᴠꜞᴒᴟᴠ꞉ꜝꜜ᷅ͼᴁⱳᴒͼԜᴐᴡ꞉ᴣᴒͼᴡᴟᴒԜᴡꜛᴒꜜᴡͼ
ᴑꜝᴠᴒͼ꞉ꜜͼᴒԜᴐⱳͼԜᴐᴡ꞉ᴣᴒͼᴡᴟᴒԜᴡꜛᴒꜜᴡͼԜᴟꜛͼᴡꜝͼꜞꞌԜᴐᴒԝꜝͼᴟԜᴡ꞉ꜝͼᴤԜᴠͼᴠᴒᴡͼԜᴡͼ᷈ⱡ᷿᷈᷅᷅ͼⱨͼ᷈᷇Ӽͼꜛ꞉ᴠᴠ꞉ꜜⱲͼ
ᴑԜᴡԜ᷆ᴑᴟꜝꜞꜝᴢᴡͼᴟԜᴡᴒͼⱱꜝᴟͼԝꜝᴡⱳͼԜᴐᴡ꞉ᴣᴒͼᴡᴟᴒԜᴡꜛᴒꜜᴡͼԜꜜᴑͼꜞꞌԜᴐᴒԝꜝͼᴤԜᴠͼԜꞌᴠꜝͼԝᴢ꞉ꞌᴡͼ꞉ꜜᴡꜝͼᴡⱳᴒͼᴒꜛꜞ꞉ᴟ꞉ᴐԜꞌͼ
ᴠԜꜛꜞꞌᴒͼᴠ꞉ᴧᴒͼᴠ꞉ꜛᴢꞌԜᴡ꞉ꜝꜜᴠ᷅
ⱴꜝᴟͼԜͼᴡᴟᴒԜᴡꜛᴒꜜᴡͼᴒⱱⱱᴒᴐᴡͼꜝⱱͼ⅍᷇Ӽͼᴟᴒᴑᴢᴐᴡ꞉ꜝꜜͼ꞉ꜜͼԜᴡᴡԜᴐꞋᴠͼԜᴠͼᴐꜝꜛꜞԜᴟᴒᴑͼᴡꜝͼꜞꞌԜᴐᴒԝꜝԓͼԜᴠᴠᴢꜛ꞉ꜜⱲͼԜͼ
ꜞꞌԜᴐᴒԝꜝͼԜᴡᴡԜᴐꞋͼᴟԜᴡᴒͼꜝⱱͼ᷊᷇᷅ͼԜᴡᴡԜᴐꞋᴠͼꜞᴒᴟͼᴤᴒᴒꞋͼꜝᴣᴒᴟͼԜͼ᷉⅍ͼᴤᴒᴒꞋͼꜞᴒᴟ꞉ꜝᴑͼⱱꜝᴟͼԜꜜͼԜᴣᴒᴟԜⱲᴒͼᴡꜝᴡԜꞌͼꜝⱱͼⅎ᷅˲ͼ
ԜᴡᴡԜᴐꞋᴠͼᴑᴢᴟ꞉ꜜⱲͼᴡⱳᴒͼᴡᴟᴒԜᴡꜛᴒꜜᴡͼꜞᴒᴟ꞉ꜝᴑԓͼԜͼᴠԜꜛꜞꞌᴒͼᴠ꞉ᴧᴒͼꜝⱱͼ᷉᷾ͼԜᴐᴡ꞉ᴣᴒꞌᴦͼᴡᴟᴒԜᴡᴒᴑͼᴠᴢԝ꞊ᴒᴐᴡᴠͼⱱꜝᴟͼᴡⱳᴒͼ
ꜞᴟ꞉ꜛԜᴟᴦͼԜᴐᴡ꞉ᴣᴒͼᴡᴟᴒԜᴡꜛᴒꜜᴡͼԜᴟꜛͼԜꜜᴑͼ᷊⅍ͼꜞꞌԜᴐᴒԝꜝͼᴠᴢԝ꞊ᴒᴐᴡᴠͼᴤꜝᴢꞌᴑͼꜞᴟꜝᴣ꞉ᴑᴒͼԜᴡͼꞌᴒԜᴠᴡͼⱠ᷿ӼͼꜞꜝᴤᴒᴟͼӿԜᴡͼ
ԜꞌꜞⱳԜⱤ᷿᷇᷅᷇᷉ԓͼꜝꜜᴒ᷄ᴠ꞉ᴑᴒᴑԐ᷅ͼⱨͼ⅍᷇Ӽͼᴟᴒᴑᴢᴐᴡ꞉ꜝꜜͼ꞉ᴠͼᴤᴒꞌꞌͼԝᴒꞌꜝᴤͼᴡⱳᴒͼᴠꜛԜꞌꞌᴒᴠᴡͼᴒᴥꜞᴒᴐᴡᴒᴑͼᴟᴒᴑᴢᴐᴡ꞉ꜝꜜͼ꞉ꜜͼ
ԜᴡᴡԜᴐꞋᴠԓͼⱱꜝᴟͼ꞉ꜜͼᴡⱳᴒͼⱫᴅ᷄᷉Ⱡ᷊᷇᷄᷇᷉ͼᴠᴡᴢᴑᴦԓͼᴤᴒͼꜝԝᴠᴒᴟᴣᴒᴑͼᴟᴒᴑᴢᴐᴡ꞉ꜝꜜᴠͼꜝⱱͼԜᴡᴡԜᴐꞋᴠͼꜝⱱͼꜜᴒԜᴟͼ᷈᷇᷇Ӽ᷅ͼᴁⱳᴒᴠᴒͼ
ᴠԜꜛꜞꞌᴒͼᴠ꞉ᴧᴒᴠͼᴤ꞉ꞌꞌͼԜꞌᴠꜝͼꜞᴟꜝᴣ꞉ᴑᴒͼԜᴑᴒꜟᴢԜᴡᴒꞌᴦͼᴠ꞉ᴧᴒᴑͼᴠԜⱱᴒᴡᴦͼꜞꜝꜞᴢꞌԜᴡ꞉ꜝꜜͼⱱꜝᴟͼᴒᴣԜꞌᴢԜᴡ꞉ꜝꜜ᷅ͼᴂꜞͼᴡꜝͼ᷈᷉᷇ͼ
ᴠᴢԝ꞊ᴒᴐᴡᴠͼӿԜꜞꜞᴟꜝᴥ꞉ꜛԜᴡᴒꞌᴦͼ˲᷇ͼᴠᴢԝ꞊ᴒᴐᴡᴠͼ꞉ꜜͼᴡⱳᴒͼ᷊ͼԜᴐᴡ꞉ᴣᴒͼᴡᴟᴒԜᴡꜛᴒꜜᴡͼⱲᴟꜝᴢꜞᴠͼԜꜜᴑͼ᷾᷇ͼ꞉ꜜͼᴡⱳᴒͼꜞꞌԜᴐᴒԝꜝͼ
ⱲᴟꜝᴢꜞԐͼꜛԜᴦͼԝᴒͼᴒꜜᴟꜝꞌꞌᴒᴑͼᴡꜝͼԜᴐᴐꜝᴢꜜᴡͼⱱꜝᴟͼꜞꜝᴡᴒꜜᴡ꞉ԜꞌͼᴒԜᴟꞌᴦͼᴑᴟꜝꜞꜝᴢᴡᴠͼᴑᴢᴟ꞉ꜜⱲͼᴡⱳᴒͼᴠᴡᴢᴑᴦ᷅ͼ
Statistical Methods: 
ᴁⱳᴒͼꜞᴟ꞉ꜛԜᴟᴦͼԜꜜԜꞌᴦᴠ꞉ᴠͼᴤ꞉ꞌꞌͼԝᴒͼᴡꜝͼᴐꜝꜛꜞԜᴟᴒͼᴡⱳᴒͼꜞᴟ꞉ꜛԜᴟᴦͼᴒꜜᴑꜞꜝ꞉ꜜᴡԓͼᴤⱳ꞉ᴐⱳͼ꞉ᴠͼᴡⱳᴒͼꜜᴢꜛԝᴒᴟͼꜝⱱͼ
ⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟ᷄ᴐꜝꜜⱱ꞉ᴟꜛᴒᴑͼⱶⱨⱬͼԜᴡᴡԜᴐꞋᴠͼꜝԝᴠᴒᴟᴣᴒᴑͼ꞉ꜜͼᴒԜᴐⱳͼⱫᴅ᷄᷉Ⱡ᷊᷇ͼᴡᴟᴒԜᴡꜛᴒꜜᴡͼԜᴟꜛͼᴡꜝͼᴡⱳԜᴡͼ꞉ꜜͼᴡⱳᴒͼ
ꜞꞌԜᴐᴒԝꜝͼԜᴟꜛͼᴑᴢᴟ꞉ꜜⱲͼᴡⱳᴒͼᴒⱱⱱ꞉ᴐԜᴐᴦͼԜᴠᴠᴒᴠᴠꜛᴒꜜᴡͼꜞᴒᴟ꞉ꜝᴑͼӿⱫԜᴦͼ᷇ͼᴡⱳᴟꜝᴢⱲⱳͼⱫԜᴦͼ᷈˲᷉Ԑ᷅ͼⱴꜝᴟͼᴡⱳᴒͼꜞᴟ꞉ꜛԜᴟᴦͼ
ᴒꜜᴑꜞꜝ꞉ꜜᴡԓͼԜꜜͼԜꜜԜꞌᴦᴠ꞉ᴠͼꜝⱱͼԜꞌꞌͼᴟԜꜜᴑꜝꜛ꞉ᴧᴒᴑͼᴠᴢԝ꞊ᴒᴐᴡᴠͼᴤⱳꜝͼⱳԜᴣᴒͼᴟᴒᴐᴒ꞉ᴣᴒᴑͼԜᴡͼꞌᴒԜᴠᴡͼ᷈ᴑꜝᴠᴒͼꜝⱱͼⱷꜚ͟ͼꜝᴟͼ
ꜞꞌԜᴐᴒԝꜝͼӿⱷᴁᴁͼꜞꜝꜞᴢꞌԜᴡ꞉ꜝꜜԐͼᴤ꞉ꞌꞌͼԝᴒͼᴐꜝꜜᴑᴢᴐᴡᴒᴑ᷅ͼ
ᴁⱳᴒͼꜞᴟ꞉ꜛԜᴟᴦͼᴒⱱⱱ꞉ᴐԜᴐᴦͼᴒꜜᴑꜞꜝ꞉ꜜᴡԓͼꜜᴢꜛԝᴒᴟͼꜝⱱͼⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟ᷄ᴐꜝꜜⱱ꞉ᴟꜛᴒᴑͼⱶⱨⱬͼԜᴡᴡԜᴐꞋᴠͼᴑᴢᴟ꞉ꜜⱲͼᴡⱳᴒͼ
ᴒⱱⱱ꞉ᴐԜᴐᴦͼᴒᴣԜꞌᴢԜᴡ꞉ꜝꜜͼꜞᴒᴟ꞉ꜝᴑͼӿⱫԜᴦͼ᷇ͼᴡⱳᴟꜝᴢⱲⱳͼⱫԜᴦͼ᷈˲᷉Ԑԓͼᴤ꞉ꞌꞌͼԝᴒͼᴐꜝꜛꜞԜᴟᴒᴑͼⱱꜝᴟͼᴒԜᴐⱳͼԜᴐᴡ꞉ᴣᴒͼ
ᴡᴟᴒԜᴡꜛᴒꜜᴡͼⱲᴟꜝᴢꜞͼӿⱫᴅ᷄᷉Ⱡ᷊᷇ԐͼᴡꜝͼᴡⱳᴒͼꜞꞌԜᴐᴒԝꜝͼⱲᴟꜝᴢꜞͼᴢᴠ꞉ꜜⱲͼԜͼⱲᴒꜜᴒᴟԜꞌ꞉ᴧᴒᴑͼꞌ꞉ꜜᴒԜᴟͼꜛꜝᴑᴒꞌͼⱱꜝᴟͼᴐꜝᴢꜜᴡͼ
ᴑԜᴡԜͼԜᴠᴠᴢꜛ꞉ꜜⱲͼԜͼ͟ꜝ꞉ᴠᴠꜝꜜͼᴑ꞉ᴠᴡᴟ꞉ԝᴢᴡ꞉ꜝꜜͼᴤ꞉ᴡⱳͼԜͼꞌꜝⱲͼꞌ꞉ꜜꞋͼⱱᴢꜜᴐᴡ꞉ꜝꜜͼԜꜜᴑͼ͟ᴒԜᴟᴠꜝꜜͼᴐⱳ꞉᷄ᴠꜟᴢԜᴟᴒͼᴠᴐԜꞌ꞉ꜜⱲͼ
ꜝⱱͼᴠᴡԜꜜᴑԜᴟᴑͼᴒᴟᴟꜝᴟᴠͼᴡꜝͼԜᴐᴐꜝᴢꜜᴡͼⱱꜝᴟͼꜞꜝᴡᴒꜜᴡ꞉Ԝꞌͼꜝᴣᴒᴟᴑ꞉ᴠꜞᴒᴟᴠ꞉ꜝꜜ᷅ͼᴁⱳᴒͼꜛꜝᴑᴒꞌͼᴤ꞉ꞌꞌͼ꞉ꜜᴐꞌᴢᴑᴒͼⱱ꞉ᴥᴒᴑͼ
ᴒⱱⱱᴒᴐᴡᴠͼⱱꜝᴟͼᴡᴟᴒԜᴡꜛᴒꜜᴡͼⱲᴟꜝᴢꜞͼӿᴐԜᴡᴒⱲꜝᴟ꞉ᴐԜꞌԐͼԜꜜᴑͼᴡⱳᴒͼꜜꜝᴟꜛԜꞌ꞉ᴧᴒᴑͼԝԜᴠᴒꞌ꞉ꜜᴒͼԜᴡᴡԜᴐꞋͼᴟԜᴡᴒͼӿᴐꜝꜜᴡ꞉ꜜᴢꜝᴢᴠԐԓͼ
ԜꜜᴑͼᴡⱳᴒͼꞌꜝⱲԜᴟ꞉ᴡⱳꜛͼꜝⱱͼᴡ꞉ꜛᴒͼ꞉ꜜͼᴑԜᴦᴠͼᴒԜᴐⱳͼᴠᴢԝ꞊ᴒᴐᴡͼᴤԜᴠͼꜝԝᴠᴒᴟᴣᴒᴑͼᴑᴢᴟ꞉ꜜⱲͼᴡⱳᴒͼᴒⱱⱱ꞉ᴐԜᴐᴦͼᴒᴣԜꞌᴢԜᴡ꞉ꜝꜜͼ
ꜞᴒᴟ꞉ꜝᴑͼᴤ꞉ꞌꞌͼԝᴒͼᴢᴠᴒᴑͼԜᴠͼԜꜜͼꜝⱱⱱᴠᴒᴡͼᴣԜᴟ꞉Ԝԝꞌᴒͼ꞉ꜜͼᴡⱳᴒͼꜛꜝᴑᴒꞌ᷅ͼ
ⱴᴟꜝꜛͼᴡⱳ꞉ᴠͼꜛꜝᴑᴒꞌԓͼᴡⱳᴒͼꞌᴒԜᴠᴡͼᴠꜟᴢԜᴟᴒᴠͼꜛᴒԜꜜͼᴟԜᴡᴒͼԜꜜᴑͼᴠᴡԜꜜᴑԜᴟᴑͼᴒᴟᴟꜝᴟͼⱱꜝᴟͼᴒԜᴐⱳͼᴡᴟᴒԜᴡꜛᴒꜜᴡͼⱲᴟꜝᴢꜞͼԜᴠͼ
ᴤᴒꞌꞌͼԜᴠͼᴡⱳᴒͼꜛᴒԜꜜͼᴟԜᴡᴒͼᴟԜᴡ꞉ꜝᴠͼᴟᴒꞌԜᴡ꞉ᴣᴒͼᴡꜝͼᴡⱳᴒͼꜞꞌԜᴐᴒԝꜝͼⱲᴟꜝᴢꜞͼԜꜜᴑͼᴐꜝᴟᴟᴒᴠꜞꜝꜜᴑ꞉ꜜⱲͼⱠ᷿Ӽͼᴐꜝꜜⱱ꞉ᴑᴒꜜᴐᴒͼ
꞉ꜜᴡᴒᴟᴣԜꞌᴠͼⱱꜝᴟͼᴒԜᴐⱳͼԜᴐᴡ꞉ᴣᴒͼᴡᴟᴒԜᴡꜛᴒꜜᴡͼⱲᴟꜝᴢꜞͼᴤ꞉ꞌꞌͼԝᴒᴒᴠᴡ꞉ꜛԜᴡᴒᴑ᷅ͼᴁⱳᴒᴠᴒͼᴒᴠᴡ꞉ꜛԜᴡᴒᴠͼᴤ꞉ꞌꞌͼԝᴒͼᴟᴒꜞꜝᴟᴡᴒᴑͼ
ԜᴠͼꜛᴒԜꜜͼᴒᴣᴒꜜᴡͼᴟԜᴡᴒᴠͼꜞᴒᴟͼᴢꜜ꞉ᴡͼꜝⱱͼᴡ꞉ꜛᴒͼӿᴤᴒᴒꞋͼԜꜜᴑͼꜛꜝꜜᴡⱳꞌᴦԐͼԝᴦͼᴡᴟԜꜜᴠⱱꜝᴟꜛ꞉ꜜⱲͼᴡⱳᴒͼᴒᴠᴡ꞉ꜛԜᴡᴒᴠͼᴢᴠ꞉ꜜⱲͼ
ᴡⱳᴒͼᴒᴥꜞꜝꜜᴒꜜᴡ꞉Ԝꞌͼⱱᴢꜜᴐᴡ꞉ꜝꜜͼԜꜜᴑͼᴠᴐԜꞌ꞉ꜜⱲͼԝᴦͼᴡⱳᴒͼᴢꜜ꞉ᴡͼꜝⱱͼᴡ꞉ꜛᴒ᷅ͼ
ᴁⱳᴒͼꜞᴟ꞉ꜛԜᴟᴦͼᴒꜜᴑꜞꜝ꞉ꜜᴡͼᴤ꞉ꞌꞌͼԝᴒͼᴡᴒᴠᴡᴒᴑͼԝᴦͼᴡⱳᴒͼⱱꜝꞌꞌꜝᴤ꞉ꜜⱲͼⱳᴦꜞꜝᴡⱳᴒᴠ꞉ᴠⱡ
ⱶ᷇ⱡͼȜⱫᴅ᷄᷉Ⱡ᷊᷇᷆ͼȜꜞꞌԜᴐᴒԝꜝⱤͼ᷈ͼᴣᴒᴟᴠᴢᴠͼⱶ᷈ⱡͼȜⱫᴅ᷄᷉Ⱡ᷊᷇᷆ͼȜꜞꞌԜᴐᴒԝꜝᶌͼ᷈
ᴄⱳᴒᴟᴒͼȜⱫᴅ᷄᷉Ⱡ᷊᷇ᴟᴒⱱᴒᴟᴠͼᴡꜝͼᴡⱳᴒͼꜛᴒԜꜜͼⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟ᷄ᴐꜝꜜⱱ꞉ᴟꜛᴒᴑͼⱶⱨⱬͼԜᴡᴡԜᴐꞋͼᴟԜᴡᴒͼ꞉ꜜͼᴡⱳᴒͼⱫᴅ᷄᷉Ⱡ᷊᷇ͼ

Ⱬᴅ᷄᷉Ⱡ᷊᷇
ⱪꞌ꞉ꜜ꞉ᴐԜꞌͼᴁᴟ꞉Ԝꞌͼ͟ᴟꜝᴡꜝᴐꜝꞌⱡͼⱫᴅ᷄᷉Ⱡ᷊᷊᷇᷄᷇
ⱨꜛᴒꜜᴑꜛᴒꜜᴡͼ᷊᷅᷇ⱴ꞉ꜜԜꞌⱡͼ᷇ⱠͼꜗԜꜜᴢԜᴟᴦ᷉᷇᷈ⅎ
ⱪꜝꜜⱱ꞉ᴑᴒꜜᴡ꞉Ԝꞌ
͟ԜⱲᴒͼ᷈ⅎ
ⱫᴦԜᴥͼⱪꜝᴟꜞ᷅
ⱲᴟꜝᴢꜞͼԜꜜᴑͼȜꜞꞌԜᴐᴒԝꜝͼᴟᴒⱱᴒᴟᴠͼᴡꜝͼᴡⱳᴒͼꜛᴒԜꜜͼⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟ᷄ᴐꜝꜜⱱ꞉ᴟꜛᴒᴑͼⱶⱨⱬͼԜᴡᴡԜᴐꞋͼᴟԜᴡᴒͼ꞉ꜜͼᴡⱳᴒͼꜞꞌԜᴐᴒԝꜝͼ
Ⱳᴟꜝᴢꜞ᷅ͼᴁⱳᴒͼꜜᴢꞌꞌͼⱳᴦꜞꜝᴡⱳᴒᴠ꞉ᴠͼ꞉ᴠͼᴡⱳԜᴡͼᴡⱳᴒͼꜛᴒԜꜜͼⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟ᷄ᴐꜝꜜⱱ꞉ᴟꜛᴒᴑͼⱶⱨⱬͼԜᴡᴡԜᴐꞋͼᴟԜᴡᴒͼᴟԜᴡ꞉ꜝͼ꞉ᴠͼ᷈ͼ
ӿꜜꜝͼᴑ꞉ⱱⱱᴒᴟᴒꜜᴐᴒͼԝᴒᴡᴤᴒᴒꜜͼᴡᴟᴒԜᴡꜛᴒꜜᴡͼⱲᴟꜝᴢꜞᴠԐԓͼᴣᴒᴟᴠᴢᴠͼᴡⱳᴒͼԜꞌᴡᴒᴟꜜԜᴡ꞉ᴣᴒͼⱳᴦꜞꜝᴡⱳᴒᴠ꞉ᴠͼᴡⱳԜᴡͼᴡⱳᴒͼⱶⱨⱬͼ
ԜᴡᴡԜᴐꞋͼᴟԜᴡᴒͼᴟԜᴡ꞉ꜝͼ꞉ᴠͼꜜꜝᴡͼ᷈᷅ͼⱬᴠᴡ꞉ꜛԜᴡᴒᴑͼԜᴡᴡԜᴐꞋͼᴟԜᴡᴒͼᴟԜᴡ꞉ꜝᴠͼꞌᴒᴠᴠͼᴡⱳԜꜜͼꜝꜜᴒͼᴤꜝᴢꞌᴑͼ꞉ꜜᴑ꞉ᴐԜᴡᴒͼᴡⱳԜᴡͼ
ᴠᴢԝ꞊ᴒᴐᴡᴠͼᴡᴟᴒԜᴡᴒᴑͼᴤ꞉ᴡⱳͼⱫᴅ᷄᷉Ⱡ᷊᷇ԓͼꜝꜜͼԜᴣᴒᴟԜⱲᴒԓͼⱳԜᴣᴒͼԜͼꞌꜝᴤᴒᴟͼ꞉ꜜᴐ꞉ᴑᴒꜜᴐᴒͼꜝⱱͼⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟ᷄ᴐꜝꜜⱱ꞉ᴟꜛᴒᴑͼ
ⱶⱨⱬͼԜᴡᴡԜᴐꞋᴠͼᴑᴢᴟ꞉ꜜⱲͼᴡⱳᴒͼᴒⱱⱱ꞉ᴐԜᴐᴦͼᴒᴣԜꞌᴢԜᴡ꞉ꜝꜜͼꜞᴒᴟ꞉ꜝᴑ᷅ͼᴁⱳᴒͼⱳᴦꜞꜝᴡⱳᴒᴠ꞉ᴠͼᴤ꞉ꞌꞌͼԝᴒͼᴡᴒᴠᴡᴒᴑͼᴢᴠ꞉ꜜⱲͼᴡⱳᴒͼ
ꜛꜝᴑᴒꞌ᷄ԝԜᴠᴒᴑͼꞌᴒԜᴠᴡͼᴠꜟᴢԜᴟᴒᴠͼꜛᴒԜꜜᴠͼᴒᴠᴡ꞉ꜛԜᴡᴒͼꜝⱱͼᴡⱳᴒͼᴡᴟᴒԜᴡꜛᴒꜜᴡͼᴑ꞉ⱱⱱᴒᴟᴒꜜᴐᴒͼᴢᴠ꞉ꜜⱲͼԜͼᴄԜꞌᴑ᷄ԝԜᴠᴒᴑͼ
ᴐⱳ꞉᷄ᴠꜟᴢԜᴟᴒͼᴡᴒᴠᴡ᷅
ᴁⱳᴒͼꜞᴒᴟᴐᴒꜜᴡԜⱲᴒͼᴐⱳԜꜜⱲᴒͼ꞉ꜜͼꜛᴒԜꜜͼⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟ᷄ᴐꜝꜜⱱ꞉ᴟꜛᴒᴑͼⱶⱨⱬͼԜᴡᴡԜᴐꞋͼᴟԜᴡᴒͼꜝⱱͼᴒԜᴐⱳͼԜᴐᴡ꞉ᴣᴒͼ
ᴡᴟᴒԜᴡꜛᴒꜜᴡͼⱲᴟꜝᴢꜞͼⱱᴟꜝꜛͼᴡⱳᴒͼԜᴡᴡԜᴐꞋͼᴟԜᴡᴒͼꜝⱱͼꜞꞌԜᴐᴒԝꜝͼᴤ꞉ꞌꞌͼԝᴒͼᴐԜꞌᴐᴢꞌԜᴡᴒᴑͼԜᴠͼ᷈᷇᷇ӼͼԑͼӿꜛᴒԜꜜͼᴟԜᴡᴒͼᴟԜᴡ꞉ꜝͼ
ᶮ᷈Ԑ᷅ͼᴀ꞉ꜛ꞉ꞌԜᴟꞌᴦԓͼᴡⱳᴒͼᴒᴠᴡ꞉ꜛԜᴡᴒᴑͼᴢꜞꜞᴒᴟͼԜꜜᴑͼꞌꜝᴤᴒᴟͼᴐꜝꜜⱱ꞉ᴑᴒꜜᴐᴒͼꞌ꞉ꜛ꞉ᴡᴠͼⱱꜝᴟͼᴡⱳᴒͼꜛᴒԜꜜͼᴟԜᴡᴒͼᴟԜᴡ꞉ꜝͼᴐԜꜜͼԝᴒͼ
ᴡᴟԜꜜᴠⱱꜝᴟꜛᴒᴑͼԝᴦͼᴠᴢԝᴡᴟԜᴐᴡ꞉ꜜⱲͼ᷈ͼԜꜜᴑͼꜛᴢꞌᴡ꞉ꜞꞌᴦ꞉ꜜⱲͼԝᴦͼ᷈᷇᷇ӼͼᴡꜝͼᴐԜꞌᴐᴢꞌԜᴡᴒͼⱠ᷿Ӽͼᴐꜝꜜⱱ꞉ᴑᴒꜜᴐᴒͼ꞉ꜜᴡᴒᴟᴣԜꞌᴠͼ
ⱱꜝᴟͼᴡⱳᴒͼꜞᴒᴟᴐᴒꜜᴡԜⱲᴒͼᴐⱳԜꜜⱲᴒ᷅ͼᴁⱳᴒͼꜛᴒԜꜜͼᴟԜᴡᴒͼᴟԜᴡ꞉ꜝᴠͼԜꜜᴑͼᴐꜝᴟᴟᴒᴠꜞꜝꜜᴑ꞉ꜜⱲͼⱠ᷿Ӽͼᴐꜝꜜⱱ꞉ᴑᴒꜜᴐᴒͼ꞉ꜜᴡᴒᴟᴣԜꞌᴠͼ
ᴤ꞉ꞌꞌͼԝᴒͼᴒᴠᴡ꞉ꜛԜᴡᴒᴑͼⱱᴟꜝꜛͼᴡⱳᴒͼⱲᴒꜜᴒᴟԜꞌ꞉ᴧᴒᴑͼꞌ꞉ꜜᴒԜᴟͼꜛꜝᴑᴒꞌͼԜᴠͼᴑᴒᴠᴐᴟ꞉ԝᴒᴑͼꜞᴟᴒᴣ꞉ꜝᴢᴠꞌᴦ᷅ͼ
ⱷꜜͼꜝᴟᴑᴒᴟͼᴡꜝͼꜛԜ꞉ꜜᴡԜ꞉ꜜͼᴡⱳᴒͼꜝᴣᴒᴟԜꞌꞌͼᴁᴦꜞᴒͼⱷͼᴒᴟᴟꜝᴟͼԜᴡͼ᷿᷇᷅᷇ԓͼԜͼᴐꜝꜜᴠᴒᴟᴣԜᴡ꞉ᴣᴒͼⱩꜝꜜⱱᴒᴟᴟꜝꜜ꞉᷄ԝԜᴠᴒᴑͼ
ꜞᴟꜝᴐᴒᴑᴢᴟᴒͼᴤ꞉ꞌꞌͼԝᴒͼᴢᴠᴒᴑͼⱱꜝᴟͼᴡⱳᴒͼᴐꜝꜛꜞԜᴟ꞉ᴠꜝꜜᴠͼꜝⱱͼᴒԜᴐⱳͼꜝⱱͼᴡⱳᴒͼԜᴐᴡ꞉ᴣᴒͼᴡᴟᴒԜᴡꜛᴒꜜᴡͼⱲᴟꜝᴢꜞᴠͼᴤ꞉ᴡⱳͼᴡⱳᴒͼ
ꜞꞌԜᴐᴒԝꜝͼⱲᴟꜝᴢꜞᴤ꞉ᴡⱳͼᴒꜟᴢԜꞌͼᴤᴒ꞉ⱲⱳᴡᴠͼⱱꜝᴟͼᴒԜᴐⱳͼᴡᴒᴠᴡͼᴠᴒᴡͼԜᴡͼ᷈᷅⅍ⅎӼͼᴠ꞉Ⱳꜜ꞉ⱱ꞉ᴐԜꜜᴐᴒͼꞌᴒᴣᴒꞌͼӿĮ᷊᷆Ԑ᷅
ᴁⱳᴒͼᴟԜꜜꞋͼꜝᴟᴑᴒᴟᴒᴑͼᴠᴒᴐꜝꜜᴑԜᴟᴦͼᴒꜜᴑꜞꜝ꞉ꜜᴡᴠͼᴤ꞉ꞌꞌͼԝᴒͼԜꜜԜꞌᴦᴧᴒᴑͼᴢᴠ꞉ꜜⱲͼᴡⱳᴒͼᴠԜꜛᴒͼꜛᴒᴡⱳꜝᴑͼԜᴠͼᴑᴒᴠᴐᴟ꞉ԝᴒᴑͼ
ⱱꜝᴟͼᴡⱳᴒͼꜞᴟ꞉ꜛԜᴟᴦͼᴒⱱⱱ꞉ᴐԜᴐᴦͼᴒꜜᴑꜞꜝ꞉ꜜᴡ᷅ͼᴁꜝͼԜᴑ꞊ᴢᴠᴡͼⱱꜝᴟͼᴡⱳᴒꜞꜝᴡᴒꜜᴡ꞉Ԝꞌͼꜝⱱͼ꞉ꜜⱱꞌԜᴡᴒᴑͼꜝᴣᴒᴟԜꞌꞌͼᴁᴦꜞᴒͼⱷͼᴒᴟᴟꜝᴟͼ
ᴟԜᴡᴒԓͼᴡⱳᴒͼᴟԜꜜꞋͼꜝᴟᴑᴒᴟᴒᴑͼᴠᴒᴐꜝꜜᴑԜᴟᴦͼᴒꜜᴑꜞꜝ꞉ꜜᴡᴠͼᴤ꞉ꞌꞌͼԝᴒͼᴡᴒᴠᴡᴒᴑͼ꞉ꜜͼԜͼⱱ꞉ᴥᴒᴑͼᴠᴒꜟᴢᴒꜜᴐᴒͼⱱꜝᴟͼᴒԜᴐⱳͼԜᴐᴡ꞉ᴣᴒͼ
ᴡᴟᴒԜᴡꜛᴒꜜᴡͼⱲᴟꜝᴢꜞͼᴡꜝͼꜞꞌԜᴐᴒԝꜝͼⱲᴟꜝᴢꜞͼᴐꜝꜛꜞԜᴟ꞉ᴠꜝꜜͼᴢᴠ꞉ꜜⱲͼԜͼⱲᴒꜜᴒᴟԜꞌͼⱲԜᴡᴒꞋᴒᴒꜞ꞉ꜜⱲͼԜꜞꜞᴟꜝԜᴐⱳͼ
ᴐꜝꜜᴠ꞉ᴠᴡᴒꜜᴡͼᴤ꞉ᴡⱳͼᴡⱳᴒͼꞌꜝⱲ꞉ᴐԜꞌͼᴟᴒᴠᴡᴟ꞉ᴐᴡ꞉ꜝꜜᴠͼꜝⱱͼᴡⱳᴒͼᴟԜꜜꞋͼꜝᴟᴑᴒᴟ꞉ꜜⱲͼꜝⱱͼᴡⱳᴒͼᴒꜜᴑꜞꜝ꞉ꜜᴡᴠ᷅ᴀᴒᴐꜝꜜᴑԜᴟᴦͼ
ᴒꜜᴑꜞꜝ꞉ꜜᴡᴠͼᴤ꞉ꞌꞌͼꜜꜝᴡͼԝᴒͼᴑᴒᴐꞌԜᴟᴒᴑͼᴠᴡԜᴡ꞉ᴠᴡ꞉ᴐԜꞌꞌᴦͼᴠ꞉Ⱳꜜ꞉ⱱ꞉ᴐԜꜜᴡͼᴢꜜꞌᴒᴠᴠͼᴡⱳᴒͼꜞᴟ꞉ꜛԜᴟᴦͼᴒꜜᴑꜞꜝ꞉ꜜᴡͼⱱꜝᴟͼᴡⱳԜᴡͼ
Ԝᴐᴡ꞉ᴣᴒͼᴡᴟᴒԜᴡꜛᴒꜜᴡͼⱲᴟꜝᴢꜞͼᴡꜝͼꜞꞌԜᴐᴒԝꜝͼⱲᴟꜝᴢꜞͼᴐꜝꜛꜞԜᴟ꞉ᴠꜝꜜͼ꞉ᴠͼⱱꜝᴢꜜᴑͼᴡꜝͼԝᴒͼᴠᴡԜᴡ꞉ᴠᴡ꞉ᴐԜꞌꞌᴦͼᴠ꞉Ⱳꜜ꞉ⱱ꞉ᴐԜꜜᴡ᷅
Safety Analysis:
ᴁᴟᴒԜᴡꜛᴒꜜᴡ᷄ᴒꜛᴒᴟⱲᴒꜜᴡͼⱨⱬᴠͼԜᴟᴒͼᴑᴒⱱ꞉ꜜᴒᴑͼԜᴠͼⱨⱬᴠͼᴤ꞉ᴡⱳͼꜝꜜᴠᴒᴡͼԜᴡͼᴡⱳᴒͼᴡ꞉ꜛᴒͼꜝⱱͼꜝᴟͼⱱꜝꞌꞌꜝᴤ꞉ꜜⱲͼᴡⱳᴒͼᴠᴡԜᴟᴡͼ
ꜝⱱͼᴡᴟᴒԜᴡꜛᴒꜜᴡͼᴤ꞉ᴡⱳͼᴠᴡᴢᴑᴦͼꜛᴒᴑ꞉ᴐԜᴡ꞉ꜝꜜԓͼꜝᴟͼꜛᴒᴑ꞉ᴐԜꞌͼᴐꜝꜜᴑ꞉ᴡ꞉ꜝꜜᴠͼꜞᴟᴒᴠᴒꜜᴡͼꜞᴟ꞉ꜝᴟͼᴡꜝͼᴡⱳᴒͼᴠᴡԜᴟᴡͼꜝⱱͼ
ᴡᴟᴒԜᴡꜛᴒꜜᴡͼԝᴢᴡͼ꞉ꜜᴐᴟᴒԜᴠ꞉ꜜⱲͼ꞉ꜜͼᴠᴒᴣᴒᴟ꞉ᴡᴦͼꜝᴟͼᴟᴒꞌԜᴡ꞉ꜝꜜᴠⱳ꞉ꜞͼԜᴡͼᴡⱳᴒͼᴡ꞉ꜛᴒͼꜝⱱͼꜝᴟͼⱱꜝꞌꞌꜝᴤ꞉ꜜⱲͼᴡⱳᴒͼᴠᴡԜᴟᴡͼꜝⱱͼ
ᴡᴟᴒԜᴡꜛᴒꜜᴡ᷅ͼᴁⱳᴒͼꜜᴢꜛԝᴒᴟͼԜꜜᴑͼꜞᴒᴟᴐᴒꜜᴡԜⱲᴒͼꜝⱱͼᴠᴢԝ꞊ᴒᴐᴡᴠͼᴤ꞉ᴡⱳͼᴁⱬⱨⱬᴠͼᴤ꞉ꞌꞌͼԝᴒͼᴑ꞉ᴠꜞꞌԜᴦᴒᴑͼⱱꜝᴟͼᴒԜᴐⱳͼ
ᴡᴟᴒԜᴡꜛᴒꜜᴡͼⱲᴟꜝᴢꜞͼԝᴦͼԝꜝᴑᴦͼᴠᴦᴠᴡᴒꜛͼԜꜜᴑͼꜞᴟᴒⱱᴒᴟᴟᴒᴑͼᴡᴒᴟꜛͼᴢᴠ꞉ꜜⱲͼᴡⱳᴒͼꜚᴒᴑ꞉ᴐԜꞌͼⱫ꞉ᴐᴡ꞉ꜝꜜԜᴟᴦͼⱱꜝᴟͼ
ϸᴒⱲᴢꞌԜᴡꜝᴟᴦͼⱨᴐᴡ꞉ᴣ꞉ᴡ꞉ᴒᴠͼӿꜚᴒᴑⱫϸⱨᶇԐ᷅ͼᴀᴢꜛꜛԜᴟ꞉ᴒᴠͼ꞉ꜜͼᴡᴒᴟꜛᴠͼꜝⱱͼᴠᴒᴣᴒᴟ꞉ᴡᴦͼԜꜜᴑͼᴟᴒꞌԜᴡ꞉ꜝꜜᴠⱳ꞉ꜞͼᴡꜝͼᴠᴡᴢᴑᴦͼ
ꜛᴒᴑ꞉ᴐԜᴡ꞉ꜝꜜͼᴤ꞉ꞌꞌͼԜꞌᴠꜝͼԝᴒͼꜞᴟꜝᴣ꞉ᴑᴒᴑ᷅ͼᴀᴒᴟ꞉ꜝᴢᴠͼⱨⱬᴠͼᴤ꞉ꞌꞌͼԝᴒͼᴠᴢꜛꜛԜᴟ꞉ᴧᴒᴑͼᴠᴒꜞԜᴟԜᴡᴒꞌᴦͼ꞉ꜜͼԜͼᴠ꞉ꜛ꞉ꞌԜᴟͼ
ⱱԜᴠⱳ꞉ꜝꜜ᷅ͼ͟Ԝᴡ꞉ᴒꜜᴡͼꞌ꞉ᴠᴡ꞉ꜜⱲᴠͼꜝⱱͼⱨⱬᴠͼᴐԜᴢᴠ꞉ꜜⱲͼᴑ꞉ᴠᴐꜝꜜᴡ꞉ꜜᴢԜᴡ꞉ꜝꜜͼꜝⱱͼᴠᴡᴢᴑᴦͼꜛᴒᴑ꞉ᴐԜᴡ꞉ꜝꜜԓͼⱨⱬᴠͼꞌᴒԜᴑ꞉ꜜⱲͼᴡꜝͼ
ᴑᴒԜᴡⱳԓͼᴀⱨⱬᴠͼԜꜜᴑͼⱨⱬᴀⱷͼᴤ꞉ꞌꞌͼԝᴒͼꜞᴟꜝᴑᴢᴐᴒᴑ᷅ͼ
ⱨⱬᴀⱷͼᴤ꞉ꞌꞌͼԝᴒͼԜꜜԜꞌᴦᴧᴒᴑͼԜᴐᴐꜝᴟᴑ꞉ꜜⱲͼᴡꜝͼꜞᴟ꞉ꜛԜᴟᴦͼᴀᴦᴠᴡᴒꜛͼ꜡ᴟⱲԜꜜͼⱪꞌԜᴠᴠᴒᴠͼӿᴀ꜡ⱪᴠԐͼԜꜜᴑͼ͟ᴟᴒⱱᴒᴟᴟᴒᴑͼ
ᴁᴒᴟꜛᴠͼӿ͟ᴁᴠԐͼᴑᴒᴡᴒᴟꜛ꞉ꜜᴒᴑͼԝᴦͼᴡⱳᴒͼᴠᴒԜᴟᴐⱳꜝⱱᴟᴒꞌᴒᴣԜꜜᴡᴀᴡԜꜜᴑԜᴟᴑ꞉ᴧᴒᴑͼꜚᴒᴑⱫϸⱨϷᴢᴒᴟ꞉ᴒᴠӿᴀꜚϷᴠԐ᷅ͼ
ᴀᴢꜛꜛԜᴟᴦͼᴡԜԝꞌᴒᴠͼᴤ꞉ᴡⱳͼᴀ꜡ⱪᴠͼԜꜜᴑ͟ᴁᴠԓͼⱱᴟꜝꜛͼᴡⱳᴒͼᴀꜚϷ ᴠᴒԜᴟᴐⱳᴒᴠԓ ᴤ꞉ꞌꞌͼԝᴒͼⱲᴒꜜᴒᴟԜᴡᴒᴑͼ
ꜞᴟᴒᴠᴒꜜᴡ꞉ꜜⱲᴡⱳᴒͼꜜᴢꜛԝᴒᴟͼԜꜜᴑͼꜞᴒᴟᴐᴒꜜᴡԜⱲᴒͼꜝⱱͼᴠᴢԝ꞊ᴒᴐᴡᴠͼԝᴦͼⱨⱬԓͼᴠᴒᴣᴒᴟ꞉ᴡᴦԓͼᴠᴒᴟ꞉ꜝᴢᴠꜜᴒᴠᴠԓͼԜꜜᴑͼ
ᴟᴒꞌԜᴡ꞉ꜝꜜᴠⱳ꞉ꜞͼᴡꜝͼᴠᴡᴢᴑᴦͼꜛᴒᴑ꞉ᴐԜᴡ꞉ꜝꜜ᷅
ᴂᴠԜⱲᴒͼꜝⱱͼᴐꜝꜜᴐꜝꜛ꞉ᴡԜꜜᴡͼꜛᴒᴑ꞉ᴐԜᴡ꞉ꜝꜜᴠͼӿꜝᴡⱳᴒᴟͼᴡⱳԜꜜͼᴟᴒᴠᴐᴢᴒͼꜛᴒᴑ꞉ᴐԜᴡ꞉ꜝꜜᴠԐͼᴤ꞉ꞌꞌͼԝᴒͼᴠᴢꜛꜛԜᴟ꞉ᴧᴒᴑͼ
ᴑᴒᴠᴐᴟ꞉ꜞᴡ꞉ᴣᴒꞌᴦͼⱱꜝᴟͼᴒԜᴐⱳͼꜝⱱͼᴡⱳᴒͼᴡᴟᴒԜᴡꜛᴒꜜᴡͼⱲᴟꜝᴢꜞᴠͼԜꜜᴑͼᴡⱳᴒͼᴐꜝꜛԝ꞉ꜜᴒᴑͼԜᴐᴡ꞉ᴣᴒͼᴡᴟᴒԜᴡꜛᴒꜜᴡͼⱲᴟꜝᴢꜞ᷅
ⱨᴐᴡᴢԜꞌͼᴣԜꞌᴢᴒᴠͼԜꜜᴑͼᴐⱳԜꜜⱲᴒͼⱱᴟꜝꜛͼԝԜᴠᴒꞌ꞉ꜜᴒͼ꞉ꜜͼᴣ꞉ᴡԜꞌͼᴠ꞉ⱲꜜᴠͼԜꜜᴑͼᴐꞌ꞉ꜜ꞉ᴐԜꞌͼꞌԜԝꜝᴟԜᴡꜝᴟᴦͼᴡᴒᴠᴡᴠͼᴤ꞉ꞌꞌͼԝᴒͼ
ᴠᴢꜛꜛԜᴟ꞉ᴧᴒᴑͼⱱꜝᴟͼᴒԜᴐⱳͼᴡᴟᴒԜᴡꜛᴒꜜᴡͼⱲᴟꜝᴢꜞͼᴤ꞉ᴡⱳͼᴑᴒᴠᴐᴟ꞉ꜞᴡ꞉ᴣᴒͼᴠᴡԜᴡ꞉ᴠᴡ꞉ᴐᴠͼԜᴡͼᴒԜᴐⱳͼԜᴠᴠᴒᴠᴠꜛᴒꜜᴡͼꜝԝᴡԜ꞉ꜜᴒᴑ᷅ͼ

Ⱬᴅ᷄᷉Ⱡ᷊᷇
ⱪꞌ꞉ꜜ꞉ᴐԜꞌͼᴁᴟ꞉Ԝꞌͼ͟ᴟꜝᴡꜝᴐꜝꞌⱡͼⱫᴅ᷄᷉Ⱡ᷊᷊᷇᷄᷇
ⱨꜛᴒꜜᴑꜛᴒꜜᴡͼ᷊᷅᷇ⱴ꞉ꜜԜꞌⱡͼ᷇ⱠͼꜗԜꜜᴢԜᴟᴦ᷉᷇᷈ⅎ
ⱪꜝꜜⱱ꞉ᴑᴒꜜᴡ꞉Ԝꞌ
͟ԜⱲᴒͼ᷈˲
ⱫᴦԜᴥͼⱪꜝᴟꜞ᷅
ⱴꜝᴟͼԜꞌꞌͼꞌԜԝꜝᴟԜᴡꜝᴟᴦͼᴡᴒᴠᴡᴠԓͼԜͼᴠⱳ꞉ⱱᴡͼᴡԜԝꞌᴒͼᴤ꞉ꞌꞌͼԝᴒͼꜞᴟꜝᴑᴢᴐᴒᴑͼᴠᴢꜛꜛԜᴟ꞉ᴧ꞉ꜜⱲͼᴐⱳԜꜜⱲᴒᴠͼⱱᴟꜝꜛͼꜜꜝᴟꜛԜꞌͼᴡꜝͼ
ԜԝꜜꜝᴟꜛԜꞌͼԜꜜᴑͼᴣ꞉ᴐᴒͼᴣᴒᴟᴠԜ᷅
ⱨԝꜜꜝᴟꜛԜꞌͼꜞⱳᴦᴠ꞉ᴐԜꞌͼᴒᴥԜꜛ꞉ꜜԜᴡ꞉ꜝꜜͼⱱ꞉ꜜᴑ꞉ꜜⱲᴠͼᴤ꞉ꞌꞌͼԝᴒͼꞌ꞉ᴠᴡᴒᴑ᷅
ᴁⱳᴒͼꜜᴢꜛԝᴒᴟͼԜꜜᴑͼꜞᴒᴟᴐᴒꜜᴡԜⱲᴒͼꜝⱱͼᴠᴢԝ꞊ᴒᴐᴡᴠͼᴤ꞉ᴡⱳͼꜜꜝᴟꜛԜꞌԓͼԜԝꜜꜝᴟꜛԜꞌ᷄ꜜꜝᴡͼᴐꞌ꞉ꜜ꞉ᴐԜꞌꞌᴦͼᴠ꞉Ⱳꜜ꞉ⱱ꞉ᴐԜꜜᴡԓͼԜꜜᴑͼ
ԜԝꜜꜝᴟꜛԜꞌ᷄ᴐꞌ꞉ꜜ꞉ᴐԜꞌꞌᴦͼᴠ꞉Ⱳꜜ꞉ⱱ꞉ᴐԜꜜᴡͼⱬⱪⱵͼⱱ꞉ꜜᴑ꞉ꜜⱲᴠͼᴤ꞉ꞌꞌͼԝᴒͼᴑ꞉ᴠꜞꞌԜᴦᴒᴑͼⱱꜝᴟͼᴒԜᴐⱳͼꜝⱱͼᴡⱳᴒͼᴡᴟᴒԜᴡꜛᴒꜜᴡͼ
Ⱳᴟꜝᴢꜞᴠ᷅
ⱨᴑᴑ꞉ᴡ꞉ꜝꜜԜꞌͼԜꜜԜꞌᴦᴠᴒᴠͼꜝⱱͼⱨⱬᴠԓͼᴀⱨⱬᴠԓͼᴠᴒᴣᴒᴟᴒͼⱨⱬᴠԓͼⱨⱬᴀⱷԓͼԜꜜᴑͼԜԝꜜꜝᴟꜛԜꞌͼⱱ꞉ꜜᴑ꞉ꜜⱲᴠͼᴤ꞉ꞌꞌͼԝᴒͼԝԜᴠᴒᴑͼ
ꜝꜜͼᴡⱳᴒͼᴡ꞉ꜛ꞉ꜜⱲͼӿᴀᴡᴢᴑᴦͼⱫԜᴦԐͼԜꜜᴑͼꜜᴢꜛԝᴒᴟͼꜝⱱͼꜞᴟ꞉ꜝᴟͼᴑꜝᴠᴒᴠͼꜝⱱͼᴠᴡᴢᴑᴦͼꜛᴒᴑ꞉ᴐԜᴡ꞉ꜝꜜ᷅ͼᴁⱳᴒͼ꞉ꜜᴐ꞉ᴑᴒꜜᴐᴒͼꜝⱱͼ
ⱨⱬᴠͼԝᴦͼꜛꜝꜜᴡⱳͼⱱᴟꜝꜛͼᴡⱳᴒͼᴠᴡԜᴟᴡͼꜝⱱͼᴠᴡᴢᴑᴦͼꜛᴒᴑ꞉ᴐԜᴡ꞉ꜝꜜͼᴤ꞉ꞌꞌͼԝᴒͼᴒᴥԜꜛ꞉ꜜᴒᴑͼԜꜜᴑͼᴡⱳᴒͼ꞉ꜜᴐ꞉ᴑᴒꜜᴐᴒͼԜꜛꜝꜜⱲͼ
ᴡⱳᴒͼⱱꜝᴢᴟͼᴡᴟᴒԜᴡꜛᴒꜜᴡͼԜᴟꜛᴠͼᴤ꞉ꞌꞌͼԝᴒͼᴐꜝꜛꜞԜᴟᴒᴑ᷅ͼᴁⱳᴒͼᴟԜᴡᴒͼꜝⱱͼᴠᴡᴢᴑᴦͼᴑ꞉ᴠᴐꜝꜜᴡ꞉ꜜᴢԜᴡ꞉ꜝꜜͼԜꜛꜝꜜⱲͼᴡⱳᴒͼⱱꜝᴢᴟͼ
ᴡᴟᴒԜᴡꜛᴒꜜᴡͼԜᴟꜛᴠͼᴤ꞉ꞌꞌͼԜꞌᴠꜝͼԝᴒͼᴐꜝꜛꜞԜᴟᴒᴑ᷅
Date of Amendment 3.0: ᷇ⱠͼꜗԜꜜᴢԜᴟᴦͼ᷉᷇᷈ⅎ

Ⱬᴅ᷄᷉Ⱡ᷊᷇
ⱪꞌ꞉ꜜ꞉ᴐԜꞌͼᴁᴟ꞉Ԝꞌͼ͟ᴟꜝᴡꜝᴐꜝꞌⱡͼⱫᴅ᷄᷉Ⱡ᷊᷊᷇᷄᷇
ⱨꜛᴒꜜᴑꜛᴒꜜᴡͼ᷊᷅᷇ͼⱴ꞉ꜜԜꞌⱡͼ᷇ⱠͼꜗԜꜜᴢԜᴟᴦ᷉᷇᷈ⅎ
ⱪꜝꜜⱱ꞉ᴑᴒꜜᴡ꞉Ԝꞌ
͟ԜⱲᴒͼ᷈Ⱡ
ⱫᴦԜᴥͼⱪꜝᴟꜞ᷅
Table 1.
Study Activities Schedule
Study Activities Schedule
Screening 
Visit
Run-in 
Period 1
Treatment Period2
Follow-up 
Period3
Tests and 
Assessments
Visit 1
Dose 1
Day 0
Site 
Check-
in4
Visit 2 
Dose 2
Day 14
Visit 3 
Dose 3
Day 28
Visit 4 
Dose 4
Day 42
Visit 5 
Dose 5
Day 56
Visits 6 and 7 
Doses 6 and 7
Days 70 and 
84
Visit 8 
Dose 8
Day 98
Visits 9 and 10 
Doses 9 and 10
Days 112 and 
126
Visit 11 
Dose 11
Day 140
Day 
144±1
Visits 12 and 13 
Doses 12 and 13
Days 154 and 
168
Visit 
14
Day 
182
Visit 
15
Day 
210
Visit 
16
Day 
238
Informed Consent
ᴅ
Eligibility Review
ᴅ
ᴅ
Long-term 
Prophylactic 
Therapy 
Washout5
ᴅ
Randomization 
ᴅ
Blinded IMP 
Treatment
ᴅ
ᴅ
ᴅ
ᴅ
ᴅ
ᴅ
ᴅ
ᴅ
ᴅ
ᴅ
Demographic and 
Medical History
ᴅ
C1-INH, C1q and 
C4 Testing6
ᴅ
Pregnancy Test7 
(females)
ᴅ
ᴅ
ᴅ
ᴅ
ᴅ
ᴅ
ᴅ
ᴅ
ᴅ
Vital Signs8
ᴅ
ᴅ
ᴅ
ᴅ
ᴅ
ᴅ
ᴅ
ᴅ
ᴅ
ᴅ
ᴅ
ᴅ
ᴅ
ᴅ
Physical 
Examination9
ᴅ
ᴅ
ᴅ
ᴅ
ᴅ
ᴅ
ᴅ
ᴅ
12-Lead ECG10
ᴅ
ᴅ
ᴅ
ᴅ
ᴅ
ᴅ
Clinical 
Laboratory 
Testing11
ᴅ
ᴅ
ᴅ
ᴅ
ᴅ
ᴅ
ᴅ
ᴅ
Serologies: 
HBsAg, HCV, and 
HIV
ᴅ
Concomitant 
Therapy
ᴅ
ᴅ
ᴅ
ᴅ
ᴅ
ᴅ
ᴅ
ᴅ
ᴅ
ᴅ
ᴅ
ᴅ
ᴅ
ᴅ
ᴅ
ᴅ
Adverse Events
ᴅ
ᴅ
ᴅ
ᴅ
ᴅ
ᴅ
ᴅ
ᴅ
ᴅ
ᴅ
ᴅ
ᴅ
ᴅ
ᴅ
ᴅ
ᴅ

Ⱬᴅ᷄᷉Ⱡ᷊᷇
ⱪꞌ꞉ꜜ꞉ᴐԜꞌͼᴁᴟ꞉Ԝꞌͼ͟ᴟꜝᴡꜝᴐꜝꞌⱡͼⱫᴅ᷄᷉Ⱡ᷊᷊᷇᷄᷇
ⱨꜛᴒꜜᴑꜛᴒꜜᴡͼ᷊᷅᷇ͼⱴ꞉ꜜԜꞌⱡͼ᷇ⱠͼꜗԜꜜᴢԜᴟᴦ᷉᷇᷈ⅎ
ⱪꜝꜜⱱ꞉ᴑᴒꜜᴡ꞉Ԝꞌ
͟ԜⱲᴒͼ᷉᷇
ⱫᴦԜᴥͼⱪꜝᴟꜞ᷅
ᴁԜԝꞌᴒͼ᷈᷅
ᴀᴡᴢᴑᴦͼⱨᴐᴡ꞉ᴣ꞉ᴡ꞉ᴒᴠͼᴀᴐⱳᴒᴑᴢꞌᴒ
ᴀᴡᴢᴑᴦͼⱨᴐᴡ꞉ᴣ꞉ᴡ꞉ᴒᴠͼᴀᴐⱳᴒᴑᴢꞌᴒ
ᴀᴐᴟᴒᴒꜜ꞉ꜜⱲͼ
ᴃ꞉ᴠ꞉ᴡ
ϸᴢꜜ᷄꞉ꜜͼ
͟ᴒᴟ꞉ꜝᴑͼ᷈
ᴁᴟᴒԜᴡꜛᴒꜜᴡͼ͟ᴒᴟ꞉ꜝᴑ᷉
ⱴꜝꞌꞌꜝᴤ᷄ᴢꜞͼ
͟ᴒᴟ꞉ꜝᴑ᷊
ᴁᴒᴠᴡᴠͼԜꜜᴑͼ
ⱨᴠᴠᴒᴠᴠꜛᴒꜜᴡᴠ
ᴃ꞉ᴠ꞉ᴡͼ᷈
Ⱬꜝᴠᴒͼ᷈
ⱫԜᴦͼ᷇
ᴀ꞉ᴡᴒͼ
ⱪⱳᴒᴐꞋ᷄
꞉ꜜ᷾
ᴃ꞉ᴠ꞉ᴡͼ᷉ͼ
Ⱬꜝᴠᴒͼ᷉
ⱫԜᴦͼ᷈᷾
ᴃ꞉ᴠ꞉ᴡͼ᷊ͼ
Ⱬꜝᴠᴒͼ᷊
ⱫԜᴦͼ᷉˲
ᴃ꞉ᴠ꞉ᴡͼ᷾ͼ
Ⱬꜝᴠᴒͼ᷾
ⱫԜᴦͼ᷾᷉
ᴃ꞉ᴠ꞉ᴡͼ᷿ͼ
Ⱬꜝᴠᴒͼ᷿
ⱫԜᴦͼ᷿⅍
ᴃ꞉ᴠ꞉ᴡᴠͼ⅍ͼԜꜜᴑͼⅎͼ
Ⱬꜝᴠᴒᴠͼ⅍ͼԜꜜᴑͼⅎ
ⱫԜᴦᴠͼⅎ᷇ͼԜꜜᴑͼ
˲᷾
ᴃ꞉ᴠ꞉ᴡͼ˲ͼ
Ⱬꜝᴠᴒͼ˲
ⱫԜᴦͼⱠ˲
ᴃ꞉ᴠ꞉ᴡᴠͼⱠͼԜꜜᴑͼ᷈᷇ͼ
ⱫꜝᴠᴒᴠͼⱠͼԜꜜᴑͼ᷈᷇
ⱫԜᴦᴠͼ᷈᷈᷉ͼԜꜜᴑͼ
᷈᷉⅍
ᴃ꞉ᴠ꞉ᴡͼ᷈᷈ͼ
Ⱬꜝᴠᴒͼ᷈᷈
ⱫԜᴦͼ᷈᷾᷇
ⱫԜᴦͼ
᷈᷾᷾ᶐ᷈
ᴃ꞉ᴠ꞉ᴡᴠͼ᷈᷉ͼԜꜜᴑͼ᷊᷈ͼ
Ⱬꜝᴠᴒᴠͼ᷈᷉ͼԜꜜᴑͼ᷊᷈
ⱫԜᴦᴠͼ᷿᷈᷾ͼԜꜜᴑͼ
᷈⅍˲
ᴃ꞉ᴠ꞉ᴡͼ
᷈᷾
ⱫԜᴦͼ
᷈˲᷉
ᴃ꞉ᴠ꞉ᴡͼ
᷿᷈
ⱫԜᴦͼ
᷉᷈᷇
ᴃ꞉ᴠ꞉ᴡͼ
᷈⅍
ⱫԜᴦͼ
᷊᷉˲
ⱶⱨⱬͼⱨᴡᴡԜᴐꞋͼ
ⱫԜᴡԜ᷈᷉
ᴅ
ᴅ
ᴅ
ᴅ
ᴅ
ᴅ
ᴅ
ᴅ
ᴅ
ᴅ
ᴅ
ᴅ
ᴅ
ᴅ
ᴅ
ᴅ
ϷᴢԜꞌ꞉ᴡᴦͼꜝⱱͼꜙ꞉ⱱᴒͼ
ⱨᴠᴠᴒᴠᴠꜛᴒꜜᴡᴠ᷊᷈
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͟ꜘͼⱩꞌꜝꜝᴑͼ
ᴀԜꜛꜞꞌ꞉ꜜⱲ
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͟ⱫͼᴀԜꜛꜞꞌᴒͼ
ⱪꜝꞌꞌᴒᴐᴡ꞉ꜝꜜ
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͟ꞌԜᴠꜛԜͼⱨꜜᴡ꞉᷄ⱫᴟᴢⱲͼ
ⱨꜜᴡ꞉ԝꜝᴑᴦͼᴁᴒᴠᴡ꞉ꜜⱲ
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Ⱬ꞉ᴠᴐⱳԜᴟⱲᴒͼⱱᴟꜝꜛͼ
ᴀᴡᴢᴑᴦ᷈᷾ԓ᷿᷈
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Ⱪ͟ͼⱤͼԝꞌꜝꜝᴑͼ͟ᴟᴒᴠᴠᴢᴟᴒⱢͼⱪ᷈᷄ⱷ꜠ⱶͼⱤͼⱪ᷈ͼⱷꜜⱳ꞉ԝ꞉ᴡꜝᴟⱢͼⱪꜛԜᴥⱤͼꜚԜᴥ꞉ꜛᴢꜛͼꜞꞌԜᴠꜛԜͼᴑᴟᴢⱲͼᴐꜝꜜᴐᴒꜜᴡᴟԜᴡ꞉ꜝꜜⱢͼⱬⱪⱵͼⱤͼⱬꞌᴒᴐᴡᴟꜝᴐԜᴟᴑ꞉ꜝⱲᴟԜꜛⱢͼⱶⱨⱬͼⱤͼⱳᴒᴟᴒᴑ꞉ᴡԜᴟᴦͼⱨꜜⱲ꞉ꜝᴒᴑᴒꜛԜⱢͼⱶԝᴠⱨⱲͼⱤͼ
ⱶᴒꜞԜᴡ꞉ᴡ꞉ᴠͼⱩͼᴀᴢᴟⱱԜᴐᴒͼⱨꜜᴡ꞉ⱲᴒꜜⱢͼⱶⱪᴃͼⱤͼⱶᴒꜞԜᴡ꞉ᴡ꞉ᴠͼⱪͼᴃ꞉ᴟᴢᴠⱢͼⱶⱷᴃͼⱤͼⱶᴢꜛԜꜜͼⱷꜛꜛᴢꜜꜝᴑᴒⱱ꞉ᴐ꞉ᴒꜜᴐᴦͼᴣ꞉ᴟᴢᴠⱢͼⱶϸͼⱤͼⱶᴒԜᴟᴡͼϸԜᴡᴒⱢͼⱷꜚ͟ͼⱤͼⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡ꞉ꜝꜜԜꞌͼꜚᴒᴑ꞉ᴐ꞉ꜜԜꞌͼ͟ᴟꜝᴑᴢᴐᴡⱢͼ
ꜙᴁ͟ͼⱤͼꜙꜝꜜⱲ᷄ᴡᴒᴟꜛͼ͟ᴟꜝꜞⱳᴦꞌԜᴐᴡ꞉ᴐⱢͼ꜡ꜙᴒͼⱤͼ꜡ꜞᴒꜜ᷄ꞌԜԝᴒꞌͼⱬᴥᴡᴒꜜᴠ꞉ꜝꜜⱢͼ͟ⱫͼⱤͼ͟ⱳԜᴟꜛԜᴐꜝᴑᴦꜜԜꜛ꞉ᴐⱢͼ͟ꜘͼⱤͼ͟ⱳԜᴟꜛԜᴐꜝꞋ꞉ꜜᴒᴡ꞉ᴐⱢͼϸϸͼⱤͼϸᴒᴠᴡ꞉ꜜⱲͼϸԜᴡᴒ
᷈᷅
ᴀᴢԝ꞊ᴒᴐᴡᴠͼᴤ꞉ꞌꞌͼᴢꜜᴑᴒᴟⱲꜝͼԜͼᴟᴢꜜ᷄꞉ꜜͼꜞᴒᴟ꞉ꜝᴑͼᴡꜝͼᴑᴒᴡᴒᴟꜛ꞉ꜜᴒͼᴡⱳᴒ꞉ᴟͼԝԜᴠᴒꞌ꞉ꜜᴒͼⱶⱨⱬͼԜᴡᴡԜᴐꞋͼᴟԜᴡᴒ᷅ͼ꜡ꜜꞌᴦͼᴠᴢԝ꞊ᴒᴐᴡᴠͼᴤ꞉ᴡⱳͼԜͼԝԜᴠᴒꞌ꞉ꜜᴒͼᴟԜᴡᴒͼꜝⱱͼԜᴡͼꞌᴒԜᴠᴡͼ᷈ͼⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟ᷄ᴐꜝꜜⱱ꞉ᴟꜛᴒᴑͼ
ⱶⱨⱬͼԜᴡᴡԜᴐꞋͼꜞᴒᴟͼ᷾ͼᴤᴒᴒꞋᴠͼᴤ꞉ꞌꞌͼԝᴒͼᴒꞌ꞉Ⱳ꞉ԝꞌᴒͼⱱꜝᴟͼᴒꜜᴟꜝꞌꞌꜛᴒꜜᴡͼԜꜜᴑͼᴟԜꜜᴑꜝꜛ꞉ᴧԜᴡ꞉ꜝꜜ᷅ͼᴀᴢԝ꞊ᴒᴐᴡᴠͼᴤⱳꜝͼᴒᴥꜞᴒᴟ꞉ᴒꜜᴐᴒͼ᷊ͼꜝᴟͼꜛꜝᴟᴒͼⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟ᷄ᴐꜝꜜⱱ꞉ᴟꜛᴒᴑͼԜᴡᴡԜᴐꞋᴠͼԝᴒⱱꜝᴟᴒͼᴡⱳᴒͼ
ᴒꜜᴑͼꜝⱱͼᴡⱳᴒͼ᷾ͼᴤᴒᴒꞋᴠͼᴐԜꜜͼᴒᴥ꞉ᴡͼᴡⱳᴒͼᴟᴢꜜ᷄꞉ꜜͼꜞᴒᴟ꞉ꜝᴑͼᴒԜᴟꞌᴦͼԜꜜᴑͼꜞᴟꜝᴐᴒᴒᴑͼᴡꜝͼᴒꜜᴟꜝꞌꞌꜛᴒꜜᴡͼԜꜜᴑͼᴟԜꜜᴑꜝꜛ꞉ᴧԜᴡ꞉ꜝꜜ᷅ͼᴀᴢԝ꞊ᴒᴐᴡᴠͼᴤ꞉ᴡⱳꜝᴢᴡͼԜᴡͼꞌᴒԜᴠᴡͼ᷈ͼⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟ᷄ᴐꜝꜜⱱ꞉ᴟꜛᴒᴑͼԜᴡᴡԜᴐꞋͼ
Ԝⱱᴡᴒᴟͼ᷾ͼᴤᴒᴒꞋᴠͼꜝⱱͼᴟᴢꜜ᷄꞉ꜜͼᴤ꞉ꞌꞌͼⱳԜᴣᴒͼᴡⱳᴒ꞉ᴟͼᴟᴢꜜ᷄꞉ꜜͼꜞᴒᴟ꞉ꜝᴑͼᴒᴥᴡᴒꜜᴑᴒᴑͼⱱꜝᴟͼԜꜜꜝᴡⱳᴒᴟͼ᷾ᴤᴒᴒꞋᴠԓͼᴑᴢᴟ꞉ꜜⱲͼᴤⱳ꞉ᴐⱳͼᴡ꞉ꜛᴒͼᴡⱳᴒᴦͼꜜᴒᴒᴑͼᴡꜝͼⱳԜᴣᴒͼԜᴡͼꞌᴒԜᴠᴡͼ᷉ͼⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟ᷄ᴐꜝꜜⱱ꞉ᴟꜛᴒᴑͼ
ԜᴡᴡԜᴐꞋᴠͼᴡꜝͼꜞᴟꜝᴐᴒᴒᴑͼᴡꜝͼᴒꜜᴟꜝꞌꞌꜛᴒꜜᴡͼԜꜜᴑͼᴟԜꜜᴑꜝꜛ꞉ᴧԜᴡ꞉ꜝꜜ᷅ͼᴁꜝͼԝᴒͼᴒꞌ꞉Ⱳ꞉ԝꞌᴒͼⱱꜝᴟͼᴒꜜᴟꜝꞌꞌꜛᴒꜜᴡԓͼᴠᴢԝ꞊ᴒᴐᴡᴠͼᴤⱳꜝͼⱳԜᴣᴒͼᴡⱳᴒ꞉ᴟͼᴟᴢꜜ᷄꞉ꜜͼᴒᴥᴡᴒꜜᴑᴒᴑͼꜛᴢᴠᴡͼᴐꜝꜛꜞꞌᴒᴡᴒͼᴡⱳᴒͼⱱᴢꞌꞌͼ˲᷄ᴤᴒᴒꞋͼ
ᴟᴢꜜ᷄꞉ꜜͼꜞᴒᴟ꞉ꜝᴑͼꜞᴟ꞉ꜝᴟͼᴡꜝͼᴒꜜᴡᴒᴟ꞉ꜜⱲͼᴡⱳᴒͼᴡᴟᴒԜᴡꜛᴒꜜᴡͼꜞᴒᴟ꞉ꜝᴑ᷅ͼᴀᴢԝ꞊ᴒᴐᴡᴠͼᴤⱳꜝͼᴑꜝͼꜜꜝᴡͼꜛᴒᴒᴡͼᴡⱳᴒͼꜛ꞉ꜜ꞉ꜛᴢꜛͼԜᴡᴡԜᴐꞋͼᴟԜᴡᴒͼᴑᴢᴟ꞉ꜜⱲͼᴟᴢꜜ᷄꞉ꜜͼꜝᴟͼԜᴟᴒͼꜝᴡⱳᴒᴟᴤ꞉ᴠᴒᴑᴒᴡᴒᴟꜛ꞉ꜜᴒᴑͼᴡꜝͼԝᴒͼ
꞉ꜜᴒꞌ꞉Ⱳ꞉ԝꞌᴒͼᴑᴢᴒͼᴡꜝͼᴠᴐᴟᴒᴒꜜ꞉ꜜⱲͼԜᴠᴠᴒᴠᴠꜛᴒꜜᴡᴠͼᴤ꞉ꞌꞌͼԝᴒͼᴐꜝꜜᴠ꞉ᴑᴒᴟᴒᴑͼԜͼᴠᴐᴟᴒᴒꜜͼⱱԜ꞉ꞌ᷅
᷉᷅
ᴁᴟᴒԜᴡꜛᴒꜜᴡͼ͟ᴒᴟ꞉ꜝᴑͼᴣ꞉ᴠ꞉ᴡᴠͼⱳԜᴣᴒͼԜͼᶐ᷊ͼᴑԜᴦͼᴤ꞉ꜜᴑꜝᴤԓͼᴤ꞉ᴡⱳͼԜͼꜛԜᴥ꞉ꜛᴢꜛͼꜝⱱͼ᷈ⅎͼᴑԜᴦᴠͼꜝᴟͼԜͼꜛ꞉ꜜ꞉ꜛᴢꜛͼꜝⱱͼ᷈᷈ͼᴑԜᴦᴠͼԝᴒᴡᴤᴒᴒꜜͼԜꜜᴦͼᴡᴤꜝͼᴑꜝᴠᴒᴠԓͼᴠᴡԜᴟᴡ꞉ꜜⱲͼᴤ꞉ᴡⱳͼⱫꜝᴠᴒͼ᷉ԓͼⱫԜᴦͼ᷈᷾ͼ
ᴡⱳᴟꜝᴢⱲⱳͼⱫԜᴦͼ᷈˲᷉᷅
᷊᷅
ⱴꜝᴟͼᴠᴢԝ꞊ᴒᴐᴡᴠͼᴤⱳꜝͼᴑꜝͼꜜꜝᴡͼᴟꜝꞌꞌꜝᴣᴒᴟͼ꞉ꜜᴡꜝͼ꜡ꜙⱬͼӿⱫᴅ᷄᷉Ⱡ᷊᷇᷄᷇᷾Ԑ᷅ͼⱴꜝꞌꞌꜝᴤ᷄ᴢꜞͼᴣ꞉ᴠ꞉ᴡᴠͼⱳԜᴣᴒͼԜͼᶐ᷊ͼᴑԜᴦͼᴤ꞉ꜜᴑꜝᴤ᷅
᷾᷅
ᴀ꞉ᴡᴒͼꜞᴒᴟᴠꜝꜜꜜᴒꞌͼᴐꜝꜜᴡԜᴐᴡͼᴡⱳᴒͼᴠᴢԝ꞊ᴒᴐᴡͼᴡꜝͼᴠꜝꞌ꞉ᴐ꞉ᴡͼⱱꜝᴟͼԜꜜᴦͼԜᴡᴡԜᴐꞋᴠͼꜜꜝᴡͼԜꞌᴟᴒԜᴑᴦͼᴟᴒꜞꜝᴟᴡᴒᴑͼԝᴦͼᴡⱳᴒͼᴠᴢԝ꞊ᴒᴐᴡͼꜝꜜᴐᴒͼԝᴒᴡᴤᴒᴒꜜͼᴠᴐⱳᴒᴑᴢꞌᴒᴑͼᴠ꞉ᴡᴒᴣ꞉ᴠ꞉ᴡᴠͼꜝᴟͼԜꜞꜞᴟꜝᴥ꞉ꜛԜᴡᴒꞌᴦͼⅎͼᴑԜᴦᴠͼ
ԜⱱᴡᴒᴟͼꞌԜᴠᴡͼᴐꜝꜜᴡԜᴐᴡͼᴤ꞉ᴡⱳͼᴠᴢԝ꞊ᴒᴐᴡ᷅
᷿᷅
ᴀᴢԝ꞊ᴒᴐᴡᴠͼᴤⱳꜝͼԜᴟᴒͼꜝꜜͼꞌꜝꜜⱲ᷄ᴡᴒᴟꜛͼꜞᴟꜝꜞⱳᴦꞌԜᴐᴡ꞉ᴐͼӿꜙᴁ͟ԐͼᴡⱳᴒᴟԜꜞᴦͼⱱꜝᴟͼⱶⱨⱬͼԜᴟᴒͼᴟᴒꜟᴢ꞉ᴟᴒᴑͼᴡꜝͼᴢꜜᴑᴒᴟⱲꜝͼԜͼꜛ꞉ꜜ꞉ꜛᴢꜛͼ᷉ͼᴤᴒᴒꞋͼᴤԜᴠⱳꜝᴢᴡͼꜞᴒᴟ꞉ꜝᴑͼꜞᴟ꞉ꜝᴟͼᴡꜝͼᴡⱳᴒͼᴠᴡԜᴟᴡͼꜝⱱͼᴡⱳᴒͼᴟᴢꜜ᷄
꞉ꜜͼꜞᴒᴟ꞉ꜝᴑ᷅ͼᴁⱳ꞉ᴠͼꜙᴁ͟ͼᴤԜᴠⱳꜝᴢᴡͼ꞉ᴠͼꜞᴒᴟꜛ꞉ᴡᴡᴒᴑͼԜᴠͼꞌꜝꜜⱲͼԜᴠͼᴡⱳᴒͼⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟͼᴑᴒᴡᴒᴟꜛ꞉ꜜᴒᴠͼᴡⱳԜᴡͼᴑꜝ꞉ꜜⱲͼᴠꜝͼᴤꜝᴢꞌᴑͼꜜꜝᴡͼꜞꞌԜᴐᴒͼᴡⱳᴒͼᴠᴢԝ꞊ᴒᴐᴡͼԜᴡͼԜꜜᴦͼᴢꜜᴑᴢᴒͼᴠԜⱱᴒᴡᴦͼᴟ꞉ᴠꞋͼԜꜜᴑͼᴡⱳᴒͼ
ᴠᴢԝ꞊ᴒᴐᴡͼ꞉ᴠͼԜᴡͼꞌᴒԜᴠᴡͼ᷈˲ͼᴦᴒԜᴟᴠͼꜝⱱͼԜⱲᴒ᷅ͼᴁⱳᴒͼⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟͼꜛᴢᴠᴡͼᴐꜝꜜⱱ꞉ᴟꜛͼᴡⱳԜᴡͼᴡⱳᴒͼᴠᴢԝ꞊ᴒᴐᴡͼⱳԜᴠͼᴠᴢᴐᴐᴒᴠᴠⱱᴢꞌꞌᴦͼᴐꜝꜛꜞꞌᴒᴡᴒᴑͼᴡⱳᴒͼ᷉ͼᴤᴒᴒꞋͼᴤԜᴠⱳꜝᴢᴡͼꜞᴒᴟ꞉ꜝᴑͼԝᴒⱱꜝᴟᴒͼᴡⱳᴒᴦͼᴐԜꜜͼ

Ⱬᴅ᷄᷉Ⱡ᷊᷇
ⱪꞌ꞉ꜜ꞉ᴐԜꞌͼᴁᴟ꞉Ԝꞌͼ͟ᴟꜝᴡꜝᴐꜝꞌⱡͼⱫᴅ᷄᷉Ⱡ᷊᷊᷇᷄᷇
ⱨꜛᴒꜜᴑꜛᴒꜜᴡͼ᷊᷅᷇ͼⱴ꞉ꜜԜꞌⱡͼ᷇ⱠͼꜗԜꜜᴢԜᴟᴦ᷉᷇᷈ⅎ
ⱪꜝꜜⱱ꞉ᴑᴒꜜᴡ꞉Ԝꞌ
͟ԜⱲᴒͼ᷉᷈
ⱫᴦԜᴥͼⱪꜝᴟꜞ᷅
ᴁԜԝꞌᴒͼ᷈᷅
ᴀᴡᴢᴑᴦͼⱨᴐᴡ꞉ᴣ꞉ᴡ꞉ᴒᴠͼᴀᴐⱳᴒᴑᴢꞌᴒ
ᴀᴡᴢᴑᴦͼⱨᴐᴡ꞉ᴣ꞉ᴡ꞉ᴒᴠͼᴀᴐⱳᴒᴑᴢꞌᴒ
ᴀᴐᴟᴒᴒꜜ꞉ꜜⱲͼ
ᴃ꞉ᴠ꞉ᴡ
ϸᴢꜜ᷄꞉ꜜͼ
͟ᴒᴟ꞉ꜝᴑͼ᷈
ᴁᴟᴒԜᴡꜛᴒꜜᴡͼ͟ᴒᴟ꞉ꜝᴑ᷉
ⱴꜝꞌꞌꜝᴤ᷄ᴢꜞͼ
͟ᴒᴟ꞉ꜝᴑ᷊
ᴁᴒᴠᴡᴠͼԜꜜᴑͼ
ⱨᴠᴠᴒᴠᴠꜛᴒꜜᴡᴠ
ᴃ꞉ᴠ꞉ᴡͼ᷈
Ⱬꜝᴠᴒͼ᷈
ⱫԜᴦͼ᷇
ᴀ꞉ᴡᴒͼ
ⱪⱳᴒᴐꞋ᷄
꞉ꜜ᷾
ᴃ꞉ᴠ꞉ᴡͼ᷉ͼ
Ⱬꜝᴠᴒͼ᷉
ⱫԜᴦͼ᷈᷾
ᴃ꞉ᴠ꞉ᴡͼ᷊ͼ
Ⱬꜝᴠᴒͼ᷊
ⱫԜᴦͼ᷉˲
ᴃ꞉ᴠ꞉ᴡͼ᷾ͼ
Ⱬꜝᴠᴒͼ᷾
ⱫԜᴦͼ᷾᷉
ᴃ꞉ᴠ꞉ᴡͼ᷿ͼ
Ⱬꜝᴠᴒͼ᷿
ⱫԜᴦͼ᷿⅍
ᴃ꞉ᴠ꞉ᴡᴠͼ⅍ͼԜꜜᴑͼⅎͼ
Ⱬꜝᴠᴒᴠͼ⅍ͼԜꜜᴑͼⅎ
ⱫԜᴦᴠͼⅎ᷇ͼԜꜜᴑͼ
˲᷾
ᴃ꞉ᴠ꞉ᴡͼ˲ͼ
Ⱬꜝᴠᴒͼ˲
ⱫԜᴦͼⱠ˲
ᴃ꞉ᴠ꞉ᴡᴠͼⱠͼԜꜜᴑͼ᷈᷇ͼ
ⱫꜝᴠᴒᴠͼⱠͼԜꜜᴑͼ᷈᷇
ⱫԜᴦᴠͼ᷈᷈᷉ͼԜꜜᴑͼ
᷈᷉⅍
ᴃ꞉ᴠ꞉ᴡͼ᷈᷈ͼ
Ⱬꜝᴠᴒͼ᷈᷈
ⱫԜᴦͼ᷈᷾᷇
ⱫԜᴦͼ
᷈᷾᷾ᶐ᷈
ᴃ꞉ᴠ꞉ᴡᴠͼ᷈᷉ͼԜꜜᴑͼ᷊᷈ͼ
Ⱬꜝᴠᴒᴠͼ᷈᷉ͼԜꜜᴑͼ᷊᷈
ⱫԜᴦᴠͼ᷿᷈᷾ͼԜꜜᴑͼ
᷈⅍˲
ᴃ꞉ᴠ꞉ᴡͼ
᷈᷾
ⱫԜᴦͼ
᷈˲᷉
ᴃ꞉ᴠ꞉ᴡͼ
᷿᷈
ⱫԜᴦͼ
᷉᷈᷇
ᴃ꞉ᴠ꞉ᴡͼ
᷈⅍
ⱫԜᴦͼ
᷊᷉˲
ᴒꜜᴡᴒᴟͼᴡⱳᴒͼᴟᴢꜜ᷄꞉ꜜͼꜞᴒᴟ꞉ꜝᴑ᷅
⅍᷅
ᴀԜꜛꜞꞌᴒᴠͼⱱꜝᴟͼⱪ᷈᷄ⱷ꜠ⱶԓͼⱪ᷾ԓͼԜꜜᴑͼⱪ᷈ꜟͼԜᴠᴠԜᴦᴠͼᴤ꞉ꞌꞌͼԝᴒͼꜝԝᴡԜ꞉ꜜᴒᴑͼԜᴡͼᴠᴐᴟᴒᴒꜜ꞉ꜜⱲͼⱱꜝᴟͼᴒꞌ꞉Ⱳ꞉ԝ꞉ꞌ꞉ᴡᴦͼԜᴠᴠᴒᴠᴠꜛᴒꜜᴡ᷅ͼ
ⅎ᷅
ᴁⱳᴒͼꜞᴟᴒⱲꜜԜꜜᴐᴦͼᴡᴒᴠᴡͼᴤ꞉ꞌꞌͼꜝꜜꞌᴦͼԝᴒͼᴐꜝꜜᴑᴢᴐᴡᴒᴑͼ꞉ꜜͼⱱᴒꜛԜꞌᴒᴠͼꜝⱱͼᴐⱳ꞉ꞌᴑԝᴒԜᴟ꞉ꜜⱲͼꜞꜝᴡᴒꜜᴡ꞉Ԝꞌ᷅ͼᴁᴒᴠᴡᴠͼꜞᴒᴟⱱꜝᴟꜛᴒᴑͼꜝꜜͼⱫԜᴦͼ᷇ͼԜꜜᴑͼⱫԜᴦͼ᷈˲᷉ͼꜛᴢᴠᴡͼԝᴒͼᴢᴟ꞉ꜜᴒ᷄ԝԜᴠᴒᴑ᷅ͼᴁᴒᴠᴡᴠͼ
ꜞᴒᴟⱱꜝᴟꜛᴒᴑͼԜᴡᴠᴐᴟᴒᴒꜜ꞉ꜜⱲԓͼⱫԜᴦᴠ᷉˲ԓͼ᷿⅍ԓͼⱠ˲ԓͼ᷈᷉⅍ԓͼ᷿᷈᷾ԓͼԜꜜᴑͼⱫԜᴦ᷊᷉˲ͼᴐԜꜜͼԝᴒͼᴠᴒᴟᴢꜛ᷄ꜝᴟͼᴢᴟ꞉ꜜᴒ᷄ԝԜᴠᴒᴑ᷅
˲᷅
ᴁⱳᴒᴟᴒͼ꞉ᴠͼԜͼᶐ᷿᷈ͼꜛ꞉ꜜᴢᴡᴒͼᴤ꞉ꜜᴑꜝᴤͼⱱꜝᴟͼԜꞌꞌͼᴣ꞉ᴡԜꞌͼᴠ꞉Ⱳꜜᴠ᷅ͼⱨᴡͼᴠᴡᴢᴑᴦͼᴣ꞉ᴠ꞉ᴡᴠͼ꞉ꜜͼᴤⱳ꞉ᴐⱳͼⱷꜚ͟ͼ꞉ᴠͼԜᴑꜛ꞉ꜜ꞉ᴠᴡᴒᴟᴒᴑԓͼᴣ꞉ᴡԜꞌͼᴠ꞉Ⱳꜜᴠͼ꞉ꜜᴐꞌᴢᴑ꞉ꜜⱲͼᴠ꞉ᴡᴡ꞉ꜜⱲꜝᴟͼᴠᴢꜞ꞉ꜜᴒͼⱩ͟ԓͼⱶϸԓͼԝꜝᴑᴦͼ
ᴡᴒꜛꜞᴒᴟԜᴡᴢᴟᴒԓͼԜꜜᴑͼϸϸԓͼᴤ꞉ꞌꞌͼԝᴒͼꜝԝᴡԜ꞉ꜜᴒᴑͼꜞᴟ꞉ꜝᴟͼᴡꜝͼᴑꜝᴠ꞉ꜜⱲԓͼ᷈ͼⱳꜝᴢᴟͼԜⱱᴡᴒᴟͼᴑꜝᴠ꞉ꜜⱲԓͼԜꜜᴑͼ᷉ͼⱳꜝᴢᴟᴠͼԜⱱᴡᴒᴟͼᴑꜝᴠ꞉ꜜⱲͼⱱꜝᴟͼᴡⱳᴒͼⱱ꞉ᴟᴠᴡͼ᷾ͼᴑꜝᴠᴒᴠͼᴤ꞉ᴡⱳͼᴡⱳᴒͼԜԝ꞉ꞌ꞉ᴡᴦͼᴡꜝͼᴒꞌ꞉ꜛ꞉ꜜԜᴡᴒͼᴡⱳᴒͼ᷉ͼ
ⱳꜝᴢᴟͼᴣ꞉ᴡԜꞌᴠͼⱱꜝᴟͼᴡⱳᴒͼᴟᴒꜛԜ꞉ꜜ꞉ꜜⱲͼᴑꜝᴠᴒᴠͼԝԜᴠᴒᴑͼꜝꜜͼᴡⱳᴒͼᴑ꞉ᴠᴐᴟᴒᴡ꞉ꜝꜜͼꜝⱱͼᴡⱳᴒͼⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟͼԜꜜᴑͼᴡⱳᴒͼԜԝᴠᴒꜜᴐᴒͼꜝⱱͼᴠԜⱱᴒᴡᴦͼᴠ꞉ⱲꜜԜꞌᴠ᷅
Ⱡ᷅
ⱶᴒ꞉ⱲⱳᴡͼԜꜜᴑͼᴤᴒ꞉Ⱳⱳᴡͼᴤ꞉ꞌꞌͼԝᴒͼᴐꜝꞌꞌᴒᴐᴡᴒᴑͼԜᴡͼᴡⱳᴒͼᴀᴐᴟᴒᴒꜜ꞉ꜜⱲͼᴣ꞉ᴠ꞉ᴡͼꜝꜜꞌᴦ᷅
᷈᷇᷅
ⱬⱪⱵᴠͼӿᴠ꞉ꜜⱲꞌᴒͼᴟᴒᴐꜝᴟᴑ꞉ꜜⱲᴠԐͼԜᴟᴒͼᴐꜝꞌꞌᴒᴐᴡᴒᴑͼԜᴡͼᴠᴐᴟᴒᴒꜜ꞉ꜜⱲԓͼԝԜᴠᴒꞌ꞉ꜜᴒͼꜞᴟ꞉ꜝᴟͼᴡꜝͼⱫꜝᴠᴒͼ᷈ԓͼⱫԜᴦͼ᷿⅍ԓͼⱫԜᴦͼ᷈᷾᷾ᶐ᷈ͼᴑԜᴦͼᴡꜝͼᴐԜꜞᴡᴢᴟᴒͼᴡⱳᴒͼᴒᴠᴡ꞉ꜛԜᴡᴒᴑⱪꜛԜᴥԜꜜᴑͼⱫԜᴦͼ᷈˲᷉᷅ͼᴁⱳᴒͼⱬⱪⱵͼ
ԜᴠᴠᴒᴠᴠꜛᴒꜜᴡͼԜᴡͼⱪꜛԜᴥꜝꜜͼⱫԜᴦͼ᷈᷾᷾ᶐ᷈ᴑԜᴦͼꜛԜᴦͼԝᴒͼꜞᴒᴟⱱꜝᴟꜛᴒᴑͼᴣ꞉ԜͼԜᴡ᷄ⱳꜝꜛᴒͼꜜᴢᴟᴠᴒͼꜝᴟͼᴡᴒᴐⱳꜜ꞉ᴐ꞉Ԝꜜͼ꞉ꜜͼꞌ꞉ᴒᴢͼꜝⱱͼԜͼᴠᴢԝ꞊ᴒᴐᴡͼᴣ꞉ᴠ꞉ᴡͼᴡꜝͼᴡⱳᴒͼᴠᴡᴢᴑᴦͼᴠ꞉ᴡᴒ᷅
᷈᷈᷅
ⱪꞌ꞉ꜜ꞉ᴐԜꞌͼꞌԜԝꜝᴟԜᴡꜝᴟᴦͼᴡᴒᴠᴡ꞉ꜜⱲͼᴤ꞉ꞌꞌͼ꞉ꜜᴐꞌᴢᴑᴒͼⱶᴒꜛԜᴡꜝꞌꜝⱲᴦԓͼⱪꜝԜⱲᴢꞌԜᴡ꞉ꜝꜜԓͼᴀᴒᴟᴢꜛͼⱪⱳᴒꜛ꞉ᴠᴡᴟᴦԓͼԜꜜᴑͼᴂᴟ꞉ꜜԜꞌᴦᴠ꞉ᴠ᷅ͼ
᷈᷉᷅
ⱶ꞉ᴠᴡꜝᴟ꞉ᴐԜꞌͼԜᴡᴡԜᴐꞋͼ꞉ꜜⱱꜝᴟꜛԜᴡ꞉ꜝꜜͼᴤ꞉ꞌꞌͼԝᴒͼᴐꜝꞌꞌᴒᴐᴡᴒᴑͼԜᴡͼᴠᴐᴟᴒᴒꜜ꞉ꜜⱲ᷅ͼⱫᴢᴟ꞉ꜜⱲͼᴡⱳᴒᴠᴡᴢᴑᴦͼᴠᴢԝ꞊ᴒᴐᴡᴠͼӿꜝᴟͼᴐԜᴟᴒⱲ꞉ᴣᴒᴟᴠԓͼ꞉ꜜͼᴡⱳᴒͼᴒᴣᴒꜜᴡͼᴡⱳᴒͼᴠᴢԝ꞊ᴒᴐᴡͼ꞉ᴠͼⱣͼ᷈˲ͼᴦᴒԜᴟᴠͼꜝꞌᴑͼꜝᴟͼ꞉ᴠͼ
꞉ꜜᴐԜꜞԜᴐ꞉ᴡԜᴡᴒᴑԐͼԜᴟᴒͼ꞉ꜜᴠᴡᴟᴢᴐᴡᴒᴑͼᴡꜝͼᴟᴒꜞꜝᴟᴡͼᴑᴒᴡԜ꞉ꞌᴠͼꜝⱱͼᴡⱳᴒͼԜᴡᴡԜᴐꞋͼᴡꜝͼᴡⱳᴒͼᴠᴡᴢᴑᴦͼᴠ꞉ᴡᴒͼᴤ꞉ᴡⱳ꞉ꜜͼⅎ᷉ͼⱳꜝᴢᴟᴠͼꜝⱱͼᴡⱳᴒͼꜝꜜᴠᴒᴡͼꜝⱱͼᴡⱳᴒͼԜᴡᴡԜᴐꞋ᷅ͼᴀ꞉ᴡᴒͼꜞᴒᴟᴠꜝꜜꜜᴒꞌͼᴤ꞉ꞌꞌͼԜꞌᴠꜝͼᴐꜝꜜᴡԜᴐᴡͼᴡⱳᴒͼ
ᴠᴢԝ꞊ᴒᴐᴡͼꜝꜜᴐᴒͼԜ ᴤᴒᴒꞋͼꜝᴟͼԜᴡͼԜꜞꜞᴟꜝᴥ꞉ꜛԜᴡᴒꞌᴦͼⅎͼᴑԜᴦᴠͼԜⱱᴡᴒᴟͼꞌԜᴠᴡͼᴐꜝꜜᴡԜᴐᴡͼᴤ꞉ᴡⱳͼᴡⱳᴒͼᴠᴢԝ꞊ᴒᴐᴡͼᴑᴢᴟ꞉ꜜⱲͼᴡⱳᴒͼᴟᴢꜜ᷄꞉ꜜͼꜞᴒᴟ꞉ꜝᴑͼԜꜜᴑͼꜝꜜᴐᴒͼԝᴒᴡᴤᴒᴒꜜͼᴠᴡᴢᴑᴦͼᴣ꞉ᴠ꞉ᴡᴠͼꜝᴟͼԜꜞꜞᴟꜝᴥ꞉ꜛԜᴡᴒꞌᴦͼⅎͼ
ᴑԜᴦᴠͼԜⱱᴡᴒᴟͼꞌԜᴠᴡͼᴐꜝꜜᴡԜᴐᴡͼᴤ꞉ᴡⱳͼᴡⱳᴒͼᴠᴢԝ꞊ᴒᴐᴡͼᴑᴢᴟ꞉ꜜⱲͼᴡⱳᴒͼᴡᴟᴒԜᴡꜛᴒꜜᴡͼꜞᴒᴟ꞉ꜝᴑͼ꞉ꜜͼꜝᴟᴑᴒᴟͼᴡꜝͼᴠꜝꞌ꞉ᴐ꞉ᴡͼⱱꜝᴟͼԜꜜᴦͼԜᴡᴡԜᴐꞋͼᴡⱳԜᴡͼꜛԜᴦͼⱳԜᴣᴒͼꜝᴐᴐᴢᴟᴟᴒᴑ᷅ͼⱷꜜͼԜᴑᴑ꞉ᴡ꞉ꜝꜜԓͼᴑᴢᴟ꞉ꜜⱲͼᴠᴡᴢᴑᴦͼᴣ꞉ᴠ꞉ᴡᴠԓͼ
ᴠ꞉ᴡᴒͼꜞᴒᴟᴠꜝꜜꜜᴒꞌͼᴤ꞉ꞌꞌͼᴠꜝꞌ꞉ᴐ꞉ᴡͼⱱꜝᴟͼԜꜜᴦͼꜜᴒᴤͼⱶⱨⱬͼԜᴡᴡԜᴐꞋͼ꞉ꜜⱱꜝᴟꜛԜᴡ꞉ꜝꜜͼᴡⱳԜᴡͼᴤԜᴠͼꜜꜝᴡͼⱲ꞉ᴣᴒꜜͼᴡⱳᴟꜝᴢⱲⱳͼꜞᴟ꞉ꜝᴟͼᴠᴢԝ꞊ᴒᴐᴡͼᴐꜝꜜᴡԜᴐᴡͼᴤ꞉ᴡⱳͼᴡⱳᴒͼᴠ꞉ᴡᴒ᷅
᷊᷈᷅
ϷᴢԜꞌ꞉ᴡᴦͼꜝⱱͼꞌ꞉ⱱᴒͼᴑԜᴡԜͼᴤ꞉ꞌꞌͼԝᴒͼꜝԝᴡԜ꞉ꜜᴒᴑͼᴢᴠ꞉ꜜⱲͼᴡⱳᴒͼⱬᴢᴟꜝϷꜝꜙͼⱵᴟꜝᴢꜞͼ᷿᷄Ⱬ꞉ꜛᴒꜜᴠ꞉ꜝꜜͼӿⱬϷ᷿ⱫԐͼᴀᴒꞌⱱ᷄ϸᴒꜞꜝᴟᴡͼϷᴢᴒᴠᴡ꞉ꜝꜜꜜԜ꞉ᴟᴒͼԜᴡͼꜞᴟᴒ᷄ᴑꜝᴠᴒͼꜝꜜͼⱫԜᴦᴠͼ᷇ԓͼⱠ˲ᶐ᷊ԓͼԜꜜᴑͼ᷈˲᷉ᶐ᷊ͼ
Ԝꜜᴑͼᴢᴠ꞉ꜜⱲͼᴡⱳᴒͼⱨꜜⱲ꞉ꜝᴒᴑᴒꜛԜͼϷᴢԜꞌ꞉ᴡᴦͼꜝⱱͼꜙ꞉ⱱᴒͼϷᴢᴒᴠᴡ꞉ꜝꜜꜜԜ꞉ᴟᴒͼӿⱨⱬ᷄ϷꜝꜙԐͼԜᴡͼꜞᴟᴒ᷄ᴑꜝᴠᴒͼꜝꜜͼⱫԜᴦᴠͼ᷇ԓͼ᷉˲ᶐ᷊ԓͼ᷿⅍ᶐ᷊ԓͼⱠ˲ᶐ᷊ԓͼ᷈᷉⅍ᶐ᷊ԓͼ᷿᷈᷾ᶐ᷊ԓͼԜꜜᴑͼ᷈˲᷉ᶐ᷊᷅ͼⱨꜜͼԜᴑᴑ꞉ᴡ꞉ꜝꜜԜꞌͼ
ꜟᴢԜꞌ꞉ᴡᴦͼꜝⱱͼꞌ꞉ⱱᴒͼԜᴠᴠᴒᴠᴠꜛᴒꜜᴡͼӿⱬϷ᷿ⱫͼԜꜜᴑͼⱨⱬ᷄ϷꜝꜙԐͼᴤ꞉ꞌꞌͼԝᴒͼᴐꜝꜜᴑᴢᴐᴡᴒᴑͼꜝꜜͼⱫԜᴦͼ᷊᷉˲ᶐ᷊ͼⱱꜝᴟͼᴠᴢԝ꞊ᴒᴐᴡᴠͼꜜꜝᴡͼᴒꜜᴡᴒᴟ꞉ꜜⱲͼ꜡ꜙⱬ᷅ͼ
᷈᷾᷅
ᴀᴢԝ꞊ᴒᴐᴡᴠͼᴤⱳꜝͼᴟꜝꞌꞌꜝᴣᴒᴟͼ꞉ꜜᴡꜝͼᴡⱳᴒͼ꜡ꜞᴒꜜ᷄ꜙԜԝᴒꞌͼⱬᴥᴡᴒꜜᴠ꞉ꜝꜜͼꜞᴟꜝᴡꜝᴐꜝꞌͼӿⱫᴅ᷄᷉Ⱡ᷊᷇᷄᷇᷾Ԑͼᴤ꞉ꞌꞌͼꜞᴟꜝᴣ꞉ᴑᴒͼᴐꜝꜜᴠᴒꜜᴡͼԝᴦͼⱫԜᴦͼ᷈˲᷉ͼԜꜜᴑͼᴟᴒᴐᴒ꞉ᴣᴒͼᴡⱳᴒ꞉ᴟͼⱱ꞉ᴟᴠᴡͼꜝꜞᴒꜜ᷄ꞌԜԝᴒꞌͼᴑꜝᴠᴒͼ
ⱱꜝꞌꞌꜝᴤ꞉ꜜⱲͼᴡⱳᴒͼᴐꜝꜛꜞꞌᴒᴡ꞉ꜝꜜͼꜝⱱͼԜꞌꞌͼⱫᴅ᷄᷉Ⱡ᷊᷊᷇᷄᷇ͼԜᴠᴠᴒᴠᴠꜛᴒꜜᴡᴠͼᴠᴐⱳᴒᴑᴢꞌᴒᴑͼꜝꜜͼⱫԜᴦͼ᷈˲᷉᷅ͼⱨᴡͼᴡⱳᴒͼᴐꜝꜛꜞꞌᴒᴡ꞉ꜝꜜͼꜝⱱͼᴡⱳᴒᴠᴒͼԜᴠᴠᴒᴠᴠꜛᴒꜜᴡᴠԓͼᴡⱳᴒͼᴠᴢԝ꞊ᴒᴐᴡͼᴤ꞉ꞌꞌͼԝᴒͼᴑ꞉ᴠᴐⱳԜᴟⱲᴒᴑͼ
ⱱᴟꜝꜛͼⱫᴅ᷄᷉Ⱡ᷊᷊᷇᷄᷇ͼԜꜜᴑͼᴟꜝꞌꞌͼ꞉ꜜᴡꜝͼᴡⱳᴒͼⱫᴅ᷄᷉Ⱡ᷊᷇᷄᷇᷾ͼᴠᴡᴢᴑᴦ᷅ͼ
᷿᷈᷅
ᴀᴢԝ꞊ᴒᴐᴡᴠͼᴤⱳꜝͼᴡᴒᴟꜛ꞉ꜜԜᴡᴒͼⱱᴟꜝꜛͼᴡⱳᴒͼᴠᴡᴢᴑᴦͼᴒԜᴟꞌᴦͼᴤ꞉ꞌꞌͼᴢꜜᴑᴒᴟⱲꜝͼӿ꞉ⱱͼꜞꜝᴠᴠ꞉ԝꞌᴒԐͼԜꞌꞌͼꜝⱱͼᴡⱳᴒͼԜᴠᴠᴒᴠᴠꜛᴒꜜᴡᴠͼԜꜜᴑͼꜞᴟꜝᴐᴒᴑᴢᴟᴒᴠͼԜᴠͼⱫԜᴦͼ᷈˲᷉ͼԜᴡͼᴡⱳᴒ꞉ᴟͼⱱ꞉ꜜԜꞌͼᴠᴡᴢᴑᴦͼᴣ꞉ᴠ꞉ᴡ᷅

Ⱬᴅ᷄᷉Ⱡ᷊᷇
ⱪꞌ꞉ꜜ꞉ᴐԜꞌͼᴁᴟ꞉Ԝꞌͼ͟ᴟꜝᴡꜝᴐꜝꞌⱡͼⱫᴅ᷄᷉Ⱡ᷊᷊᷇᷄᷇
ⱨꜛᴒꜜᴑꜛᴒꜜᴡͼ᷊᷅᷇ͼⱴ꞉ꜜԜꞌⱡͼ᷇ⱠͼꜗԜꜜᴢԜᴟᴦ᷉᷇᷈ⅎ
ⱪꜝꜜⱱ꞉ᴑᴒꜜᴡ꞉Ԝꞌ
͟ԜⱲᴒͼ᷉᷉
ⱫᴦԜᴥͼⱪꜝᴟꜞ᷅
TABLE OF CONTENTS
͟ϸ꜡ᴁ꜡ⱪ꜡ꜙͼᴀⱷⱵ꜠ⱨᴁᴂϸⱬͼ͟ⱨⱵⱬ᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷉
ⱨꜚⱬ꜠Ⱬꜚⱬ꜠ᴁͼᴀᴂꜚꜚⱨϸᴆͼⱨ꜠Ⱬͼϸⱨᴁⱷ꜡꜠ⱨꜙⱬ᷊᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅
ᴀᴆ꜠꜡͟ᴀⱷᴀ᷿᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅
ꜙⱷᴀᴁͼ꜡ⱴͼⱨⱩⱩϸⱬᴃⱷⱨᴁⱷ꜡꜠ᴀͼⱨ꜠ⱫͼⱫⱬⱴⱷ꜠ⱷᴁⱷ꜡꜠ᴀͼ꜡ⱴͼᴁⱬϸꜚᴀ᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷉˲
᷈
ⱷ꜠ᴁϸ꜡Ⱬᴂⱪᴁⱷ꜡꜠᷊᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷉
᷈᷅᷈
Ⱬᴅ᷄᷉Ⱡ᷊᷊᷇᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷉
᷈᷅᷉
ⱶᴒᴟᴒᴑ꞉ᴡԜᴟᴦͼⱨꜜⱲ꞉ꜝᴒᴑᴒꜛԜ᷊᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷉
᷊᷈᷅
ᴁⱳᴒᴟԜꜞᴒᴢᴡ꞉ᴐͼϸԜᴡ꞉ꜝꜜԜꞌᴒͼⱱꜝᴟͼⱫᴅ᷄᷉Ⱡ᷊᷊᷇᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷉
᷈᷅᷾
ᴀԜⱱᴒᴡᴦͼϸԜᴡ꞉ꜝꜜԜꞌᴒͼⱱꜝᴟͼⱫᴅ᷄᷉Ⱡ᷊᷊᷊᷇᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅
᷿᷈᷅
Ⱬᴅ᷄᷉Ⱡ᷊᷇ͼ꜠ꜝꜜ᷄ⱪꞌ꞉ꜜ꞉ᴐԜꞌͼ͟ⱳԜᴟꜛԜᴐꜝꞌꜝⱲᴦͼԜꜜᴑͼᴁꜝᴥ꞉ᴐꜝꞌꜝⱲᴦ᷊᷊᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅
᷈᷅⅍
Ⱬᴅ᷄᷉Ⱡ᷊᷇ͼⱪꞌ꞉ꜜ꞉ᴐԜꞌͼⱫԜᴡԜ ᷊᷊᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅
᷈᷅⅍᷅᷈
ᴀ꞉ꜜⱲꞌᴒ᷄ⱨᴠᴐᴒꜜᴑ꞉ꜜⱲͼⱫꜝᴠᴒͼᴀᴡᴢᴑᴦͼ꞉ꜜͼⱶᴒԜꞌᴡⱳᴦͼᴀᴢԝ꞊ᴒᴐᴡᴠͼӿⱫᴅ᷄᷉Ⱡ᷊᷇᷄᷇᷈Ԑ᷊᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷾
᷈᷅⅍᷅᷉
ꜚᴢꞌᴡ꞉ꜞꞌᴒ᷄ⱨᴠᴐᴒꜜᴑ꞉ꜜⱲͼⱫꜝᴠᴒͼᴀᴡᴢᴑᴦͼ꞉ꜜͼⱶⱨⱬͼ͟Ԝᴡ꞉ᴒꜜᴡᴠͼӿⱫᴅ᷄᷉Ⱡ᷊᷇᷄᷇᷉Ԑ᷊᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷾
᷉
ᴀᴁᴂⱫᴆͼ꜡Ⱪꜗⱬⱪᴁⱷᴃⱬᴀ᷊᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅ⅎ
᷉᷅᷈
͟ᴟ꞉ꜛԜᴟᴦͼ꜡ԝ꞊ᴒᴐᴡ꞉ᴣᴒ᷊᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅ⅎ
᷉᷅᷉
ᴀᴒᴐꜝꜜᴑԜᴟᴦͼ꜡ԝ꞊ᴒᴐᴡ꞉ᴣᴒ᷊᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅ⅎ
᷊᷉᷅
ᴁᴒᴟᴡ꞉Ԝᴟᴦͼ꜡ԝ꞊ᴒᴐᴡ꞉ᴣᴒᴠ᷊᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅ⅎ
᷊
ⱷ꜠ᴃⱬᴀᴁⱷⱵⱨᴁⱷ꜡꜠ⱨꜙͼ͟ꜙⱨ꜠᷊᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅˲
᷊᷅᷈
꜡ᴣᴒᴟԜꞌꞌͼᴀᴡᴢᴑᴦͼⱫᴒᴠ꞉ⱲꜜͼԜꜜᴑͼ͟ꞌԜꜜ᷊᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅˲
᷊᷅᷈᷅᷈
꜡ᴣᴒᴟᴣ꞉ᴒᴤ᷊᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅˲
᷊᷅᷈᷅᷈᷅᷈
ꜙꜝꜜⱲ᷄ᴁᴒᴟꜛͼ͟ᴟꜝꜞⱳᴦꞌԜᴐᴡ꞉ᴐͼӿꜙᴁ͟ԐͼᴁⱳᴒᴟԜꜞᴦͼᴄԜᴠⱳꜝᴢᴡ᷊᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅˲
᷊᷅᷈᷅᷈᷅᷉
ϸᴢꜜ᷄ⱷꜜͼ͟ᴒᴟ꞉ꜝᴑ᷊᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅˲
᷊᷊᷅᷈᷅᷈᷅
ᴁᴟᴒԜᴡꜛᴒꜜᴡͼ͟ᴒᴟ꞉ꜝᴑ᷊᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅Ⱡ
᷊᷅᷈᷅᷈᷅᷾
꜡ꜞᴒꜜ᷄ꜙԜԝᴒꞌͼⱬᴥᴡᴒꜜᴠ꞉ꜝꜜͼӿ꜡ꜙⱬԐ᷊᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅Ⱡ
᷊᷿᷅᷈᷅᷈᷅
ⱴꜝꞌꞌꜝᴤ᷄ᴂꜞͼ͟ᴒᴟ꞉ꜝᴑ᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷾᷇
᷊᷅᷈᷅᷉
ᴀԜⱱᴒᴡᴦͼ꜡ᴣᴒᴟᴠ꞉ⱲⱳᴡͼԜꜜᴑͼᴀᴡꜝꜞꜞ꞉ꜜⱲͼϸᴢꞌᴒᴠ᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷾᷇
᷊᷅᷈᷅᷉᷅᷈
ⱷꜜᴡᴒᴟ꞉ꜛͼⱨꜜԜꞌᴦᴠ꞉ᴠͼԜꜜᴑͼⱫԜᴡԜͼᴀԜⱱᴒᴡᴦͼꜚꜝꜜ꞉ᴡꜝᴟ꞉ꜜⱲͼⱩꜝԜᴟᴑͼӿⱫᴀꜚⱩԐ ᷅᷅᷅᷅᷅᷅᷅᷅᷅᷾᷇
᷊᷅᷈᷅᷉᷅᷉
ⱷꜜᴑ꞉ᴣ꞉ᴑᴢԜꞌͼᴀᴡꜝꜞꜞ꞉ꜜⱲͼϸᴢꞌᴒᴠ᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷾᷇
᷊᷊᷅᷈᷅
ⱴꜝꞌꞌꜝᴤ᷄ᴂꜞͼⱱꜝᴟͼᴀᴢԝ꞊ᴒᴐᴡᴠͼꜚᴒᴒᴡ꞉ꜜⱲͼᴀᴡꜝꜞꜞ꞉ꜜⱲͼⱪᴟ꞉ᴡᴒᴟ꞉Ԝ᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷾᷈
᷊᷅᷉
ϸԜᴡ꞉ꜝꜜԜꞌᴒͼⱱꜝᴟͼ͟꞉ᴣꜝᴡԜꞌͼⱫꜝᴠᴒͼᴀᴒꞌᴒᴐᴡ꞉ꜝꜜ᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷾᷈
᷊᷊᷅
ⱷꜜᴑ꞉ᴣ꞉ᴑᴢԜꞌͼᴀᴢԝ꞊ᴒᴐᴡͼⱫꜝᴠ꞉ꜜⱲͼԜꜜᴑͼⱴꜝꞌꞌꜝᴤ᷄ᴂꜞ᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷾᷉
᷊᷅᷾
ᴀᴡᴢᴑᴦͼⱫᴢᴟԜᴡ꞉ꜝꜜͼⱱꜝᴟͼⱷꜜᴑ꞉ᴣ꞉ᴑᴢԜꞌͼᴀᴢԝ꞊ᴒᴐᴡᴠ᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷾᷉
᷾
ᴀᴁᴂⱫᴆͼ͟꜡͟ᴂꜙⱨᴁⱷ꜡꜠ͼᴀⱬꜙⱬⱪᴁⱷ꜡꜠᷊᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷾
᷾᷅᷈
ᴀᴡᴢᴑᴦͼ͟ꜝꜞᴢꞌԜᴡ꞉ꜝꜜ᷊᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷾
᷾᷅᷉
ⱷꜜᴐꞌᴢᴠ꞉ꜝꜜͼⱪᴟ꞉ᴡᴒᴟ꞉Ԝ ᷊᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷾
᷊᷾᷅
ⱬᴥᴐꞌᴢᴠ꞉ꜝꜜͼⱪᴟ꞉ᴡᴒᴟ꞉Ԝ ᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷾᷾
᷿
ᴀᴁᴂⱫᴆͼᴁϸⱬⱨᴁꜚⱬ꜠ᴁӿᴀԐ᷿᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷾

Ⱬᴅ᷄᷉Ⱡ᷊᷇
ⱪꞌ꞉ꜜ꞉ᴐԜꞌͼᴁᴟ꞉Ԝꞌͼ͟ᴟꜝᴡꜝᴐꜝꞌⱡͼⱫᴅ᷄᷉Ⱡ᷊᷊᷇᷄᷇
ⱨꜛᴒꜜᴑꜛᴒꜜᴡͼ᷊᷅᷇ͼⱴ꞉ꜜԜꞌⱡͼ᷇ⱠͼꜗԜꜜᴢԜᴟᴦ᷉᷇᷈ⅎ
ⱪꜝꜜⱱ꞉ᴑᴒꜜᴡ꞉Ԝꞌ
͟ԜⱲᴒͼ᷊᷉
ⱫᴦԜᴥͼⱪꜝᴟꜞ᷅
᷿᷅᷈
Ⱬᴒᴠᴐᴟ꞉ꜞᴡ꞉ꜝꜜͼꜝⱱͼᴁᴟᴒԜᴡꜛᴒꜜᴡӿᴠԐ᷿᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷾
᷿᷅᷈᷅᷈
Ⱬᴅ᷄᷉Ⱡ᷊᷿᷇᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷾
᷿᷅᷈᷅᷉
͟ꞌԜᴐᴒԝꜝ᷿᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷾
᷿᷅᷉
Ⱬꜝᴠ꞉ꜜⱲͼԜꜜᴑͼⱴꜝꞌꞌꜝᴤ᷄ᴂꜞͼᴀᴐⱳᴒᴑᴢꞌᴒ᷿᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷾
᷿᷊᷅
ꜚᴒᴡⱳꜝᴑͼꜝⱱͼⱨᴠᴠ꞉Ⱳꜜ꞉ꜜⱲͼᴀᴢԝ꞊ᴒᴐᴡᴠͼᴡꜝͼᴁᴟᴒԜᴡꜛᴒꜜᴡͼⱵᴟꜝᴢꜞᴠ᷿᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷾
᷿᷅᷾
Ⱪꞌ꞉ꜜᴑ꞉ꜜⱲͼԜꜜᴑͼᴂꜜԝꞌ꞉ꜜᴑ꞉ꜜⱲ᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷾⅍
᷿᷿᷅
͟ᴟ꞉ꜝᴟͼԜꜜᴑͼⱪꜝꜜᴐꜝꜛ꞉ᴡԜꜜᴡͼᴁⱳᴒᴟԜꜞᴦ᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷾⅍
᷿᷿᷅᷅᷈
ⱨꞌꞌꜝᴤᴒᴑͼᴁⱳᴒᴟԜꜞ꞉ᴒᴠ᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷾⅍
᷿᷿᷅᷅᷉
ⱬᴥᴐꞌᴢᴑᴒᴑͼⱪꜝꜜᴐꜝꜛ꞉ᴡԜꜜᴡͼᴁⱳᴒᴟԜꜞ꞉ᴒᴠ᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷾ⅎ
᷿᷅⅍
ϸᴒᴠᴡᴟ꞉ᴐᴡ꞉ꜝꜜᴠ᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷾ⅎ
᷿᷅⅍᷅᷈
ꜚᴒᴑ꞉ᴐԜꞌͼⱷꜜᴡᴒᴟᴣᴒꜜᴡ꞉ꜝꜜᴠ᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷾ⅎ
᷿᷅⅍᷅᷉
ⱴꞌᴢ꞉ᴑͼԜꜜᴑͼⱴꜝꜝᴑͼⱷꜜᴡԜꞋᴒ᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷾ⅎ
᷿᷅⅍᷊᷅
ⱨᴐᴡ꞉ᴣ꞉ᴡᴦ᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷾ⅎ
᷿᷅ⅎ
ᴁᴟᴒԜᴡꜛᴒꜜᴡͼⱪꜝꜛꜞꞌ꞉Ԝꜜᴐᴒ᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷾ⅎ
᷿᷅˲
͟ԜᴐꞋԜⱲ꞉ꜜⱲͼԜꜜᴑͼꜙԜԝᴒꞌ꞉ꜜⱲ᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷾ⅎ
᷿᷅Ⱡ
ᴀᴡꜝᴟԜⱲᴒͼԜꜜᴑͼⱨᴐᴐꜝᴢꜜᴡԜԝ꞉ꞌ꞉ᴡᴦ᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷾˲
᷿᷅᷈᷇
ⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡ꞉ꜝꜜԜꞌͼꜚᴒᴑ꞉ᴐ꞉ꜜԜꞌͼ͟ᴟꜝᴑᴢᴐᴡͼϸᴒᴡᴒꜜᴡ꞉ꜝꜜͼԜᴡͼᴀᴡᴢᴑᴦͼᴀ꞉ᴡᴒ᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷾˲
⅍
ᴀᴁᴂⱫᴆͼ͟ϸ꜡ⱪⱬⱫᴂϸⱬᴀ᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷾Ⱡ
⅍᷅᷈
ⱷꜜⱱꜝᴟꜛᴒᴑͼⱪꜝꜜᴠᴒꜜᴡ᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷾Ⱡ
⅍᷅᷉
ⱬꞌ꞉Ⱳ꞉ԝ꞉ꞌ꞉ᴡᴦͼϸᴒᴣ꞉ᴒᴤ᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷾Ⱡ
⅍᷊᷅
ⱫᴒꜛꜝⱲᴟԜꜞⱳ꞉ᴐᴠͼԜꜜᴑͼꜚᴒᴑ꞉ᴐԜꞌͼⱶ꞉ᴠᴡꜝᴟᴦ᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷾Ⱡ
⅍᷅᷾
ⱬⱱⱱ꞉ᴐԜᴐᴦͼⱨᴠᴠᴒᴠᴠꜛᴒꜜᴡᴠ᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷾Ⱡ
⅍᷅᷾᷅᷈
͟ᴟ꞉ꜛԜᴟᴦͼԜꜜᴑͼᴀᴒᴐꜝꜜᴑԜᴟᴦͼⱬꜜᴑꜞꜝ꞉ꜜᴡᴠ᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷾Ⱡ
⅍᷅᷾᷅᷉
ⱶⱨⱬͼⱨᴡᴡԜᴐꞋͼⱷꜜⱱꜝᴟꜛԜᴡ꞉ꜝꜜͼⱪꜝꞌꞌᴒᴐᴡ꞉ꜝꜜ᷿᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷇
⅍᷿᷅
ᴃ꞉ᴡԜꞌͼᴀ꞉Ⱳꜜᴠ᷿᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷉
⅍᷅⅍
͟ⱳᴦᴠ꞉ᴐԜꞌͼⱬᴥԜꜛ꞉ꜜԜᴡ꞉ꜝꜜ᷿᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷉
⅍᷅ⅎ
ⱬꞌᴒᴐᴡᴟꜝᴐԜᴟᴑ꞉ꜝⱲᴟԜꜞⱳᴦͼӿⱬⱪⱵԐ ᷿᷊᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅
⅍᷅˲
ⱪꞌ꞉ꜜ꞉ᴐԜꞌͼꜙԜԝꜝᴟԜᴡꜝᴟᴦͼᴁᴒᴠᴡᴠ᷿᷊᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅
⅍᷅˲᷅᷈
ꜙԜԝꜝᴟԜᴡꜝᴟᴦͼ͟ԜᴟԜꜛᴒᴡᴒᴟᴠ᷿᷊᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅
⅍᷅˲᷅᷈᷅᷈
ⱶᴒꜛԜᴡꜝꞌꜝⱲᴦ᷿᷊᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅
⅍᷅˲᷅᷈᷅᷉
ⱪꜝԜⱲᴢꞌԜᴡ꞉ꜝꜜ᷿᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷾
⅍᷅˲᷊᷅᷈᷅
ⱪⱳᴒꜛ꞉ᴠᴡᴟᴦ᷿᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷾
⅍᷅˲᷅᷈᷅᷾
ᴂᴟ꞉ꜜԜꞌᴦᴠ꞉ᴠ᷿᷿᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅
⅍᷅˲᷿᷅᷈᷅
ᴀᴒᴟꜝꞌꜝⱲᴦ᷿᷿᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅
⅍᷅˲᷅᷈᷅⅍
͟ᴟᴒⱲꜜԜꜜᴐᴦͼᴁᴒᴠᴡ᷿᷿᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅
⅍᷅˲᷅᷈᷅ⅎ
ⱪ᷈᷄ⱷ꜠ⱶͼⱴᴢꜜᴐᴡ꞉ꜝꜜԜꞌͼⱨᴠᴠԜᴦ᷿᷿᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅
⅍᷅˲᷅᷈᷅˲
ⱪ᷾ͼⱨᴠᴠԜᴦ᷿᷿᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅
⅍᷅˲᷅᷈᷅Ⱡ
ⱪ᷈ꜟͼⱨᴠᴠԜᴦ᷿᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅⅍

Ⱬᴅ᷄᷉Ⱡ᷊᷇
ⱪꞌ꞉ꜜ꞉ᴐԜꞌͼᴁᴟ꞉Ԝꞌͼ͟ᴟꜝᴡꜝᴐꜝꞌⱡͼⱫᴅ᷄᷉Ⱡ᷊᷊᷇᷄᷇
ⱨꜛᴒꜜᴑꜛᴒꜜᴡͼ᷊᷅᷇ͼⱴ꞉ꜜԜꞌⱡͼ᷇ⱠͼꜗԜꜜᴢԜᴟᴦ᷉᷇᷈ⅎ
ⱪꜝꜜⱱ꞉ᴑᴒꜜᴡ꞉Ԝꞌ
͟ԜⱲᴒͼ᷉᷾
ⱫᴦԜᴥͼⱪꜝᴟꜞ᷅
⅍᷅˲᷅᷈᷅᷈᷇
͟ꜘͼᴀԜꜛꜞꞌᴒͼⱪꜝꞌꞌᴒᴐᴡ꞉ꜝꜜ᷿᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅⅍
⅍᷅˲᷅᷈᷅᷈᷈
͟ⱫͼᴀԜꜛꜞꞌᴒͼⱪꜝꞌꞌᴒᴐᴡ꞉ꜝꜜ᷿᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅⅍
⅍᷅˲᷅᷈᷅᷈᷉
͟ꞌԜᴠꜛԜͼⱨꜜᴡ꞉᷄ⱫᴟᴢⱲͼⱨꜜᴡ꞉ԝꜝᴑᴦͼᴁᴒᴠᴡ꞉ꜜⱲ᷿᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅⅍
⅍᷅˲᷅᷉
ᴀԜꜛꜞꞌᴒͼⱪꜝꞌꞌᴒᴐᴡ꞉ꜝꜜԓͼᴀᴡꜝᴟԜⱲᴒԓͼԜꜜᴑͼᴀⱳ꞉ꜞꜞ꞉ꜜⱲ᷿᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅⅍
⅍᷅Ⱡ
͟ⱳԜᴟꜛԜᴐꜝꞋ꞉ꜜᴒᴡ꞉ᴐͼⱨᴠᴠᴒᴠᴠꜛᴒꜜᴡᴠ᷿᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅⅍
⅍᷅᷈᷇
͟ⱳԜᴟꜛԜᴐꜝᴑᴦꜜԜꜛ꞉ᴐͼⱨᴠᴠᴒᴠᴠꜛᴒꜜᴡᴠ᷿᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅⅍
⅍᷅᷈᷈
͟ꞌԜᴠꜛԜͼⱨꜜᴡ꞉᷄ⱫᴟᴢⱲͼⱨꜜᴡ꞉ԝꜝᴑᴦͼᴁᴒᴠᴡ꞉ꜜⱲ᷿᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅⅍
⅍᷅᷈᷉
͟ᴟ꞉ꜝᴟͼԜꜜᴑͼⱪꜝꜜᴐꜝꜛ꞉ᴡԜꜜᴡͼᴁⱳᴒᴟԜꜞᴦ᷿᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅ⅎ
⅍᷊᷅᷈
ϸԜꜜᴑꜝꜛ꞉ᴧԜᴡ꞉ꜝꜜ᷿᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅ⅎ
⅍᷅᷈᷾
ⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡ꞉ꜝꜜԜꞌͼꜚᴒᴑ꞉ᴐ꞉ꜜԜꞌͼ͟ᴟꜝᴑᴢᴐᴡͼᴁᴟᴒԜᴡꜛᴒꜜᴡ᷿᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅ⅎ
⅍᷿᷅᷈
ϷᴢԜꞌ꞉ᴡᴦͼꜝⱱͼꜙ꞉ⱱᴒͼⱨᴠᴠᴒᴠᴠꜛᴒꜜᴡᴠ᷿᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅ⅎ
⅍᷅᷈⅍
ⱨᴑᴣᴒᴟᴠᴒͼⱬᴣᴒꜜᴡͼϸᴒꜞꜝᴟᴡ꞉ꜜⱲ᷿᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅ⅎ
⅍᷅᷈⅍᷅᷈
Ⱬᴒⱱ꞉ꜜ꞉ᴡ꞉ꜝꜜᴠ᷿᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅ⅎ
⅍᷅᷈⅍᷅᷈᷅᷈
ⱨᴑᴣᴒᴟᴠᴒͼⱬᴣᴒꜜᴡ᷿᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅ⅎ
⅍᷅᷈⅍᷅᷈᷅᷉
ᴀᴒᴟ꞉ꜝᴢᴠͼⱨᴑᴣᴒᴟᴠᴒͼⱬᴣᴒꜜᴡ᷿᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅˲
⅍᷅᷈⅍᷊᷅᷈᷅
꜡ᴣᴒᴟᴑꜝᴠᴒ᷿᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅Ⱡ
⅍᷅᷈⅍᷅᷈᷅᷾
͟ꞌԜꜜꜜᴒᴑͼⱶꜝᴠꜞ꞉ᴡԜꞌ꞉ᴧԜᴡ꞉ꜝꜜ᷿᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅Ⱡ
⅍᷅᷈⅍᷿᷅᷈᷅
ᴁᴟᴒԜᴡꜛᴒꜜᴡ᷄ⱬꜛᴒᴟⱲᴒꜜᴡͼⱨᴑᴣᴒᴟᴠᴒͼⱬᴣᴒꜜᴡᴠͼӿᴁⱬⱨⱬԐ ᷿᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅Ⱡ
⅍᷅᷈⅍᷅᷈᷅⅍
ⱨᴑᴣᴒᴟᴠᴒͼⱬᴣᴒꜜᴡᴠͼꜝⱱͼᴀꜞᴒᴐ꞉ԜꞌͼⱷꜜᴡᴒᴟᴒᴠᴡͼӿⱨⱬᴀⱷԐ᷿᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅Ⱡ
⅍᷅᷈⅍᷅᷉
ꜚꜝꜜ꞉ᴡꜝᴟ꞉ꜜⱲ᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅⅍᷇
⅍᷅᷈⅍᷅᷉᷅᷈
ꜚꜝꜜ꞉ᴡꜝᴟ꞉ꜜⱲͼꜝⱱͼⱨᴑᴣᴒᴟᴠᴒͼⱬᴣᴒꜜᴡᴠ᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅⅍᷇
⅍᷅᷈⅍᷅᷉᷅᷉
ꜚꜝꜜ꞉ᴡꜝᴟ꞉ꜜⱲͼꜝⱱͼᴀԜⱱᴒᴡᴦͼꜙԜԝꜝᴟԜᴡꜝᴟᴦͼⱨᴠᴠᴒᴠᴠꜛᴒꜜᴡᴠ᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅⅍᷇
⅍᷅᷈⅍᷊᷅
ⱨᴠᴠᴒᴠᴠꜛᴒꜜᴡͼꜝⱱͼⱨᴑᴣᴒᴟᴠᴒͼⱬᴣᴒꜜᴡᴠ᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅⅍᷇
⅍᷅᷈⅍᷊᷅᷅᷈
ⱨᴠᴠᴒᴠᴠꜛᴒꜜᴡͼꜝⱱͼᴀᴒᴣᴒᴟ꞉ᴡᴦ᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅⅍᷇
⅍᷅᷈⅍᷊᷅᷅᷉
ⱨᴠᴠᴒᴠᴠꜛᴒꜜᴡͼꜝⱱͼⱪԜᴢᴠԜꞌ꞉ᴡᴦ᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅⅍᷈
⅍᷅᷈⅍᷊᷊᷅᷅
ⱨᴠᴠᴒᴠᴠꜛᴒꜜᴡͼꜝⱱͼⱪꞌ꞉ꜜ꞉ᴐԜꞌͼᴀ꞉Ⱳꜜ꞉ⱱ꞉ᴐԜꜜᴐᴒ᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅⅍᷉
⅍᷅᷈⅍᷅᷾
ⱪꞌ꞉ꜜ꞉ᴐԜꞌͼꜙԜԝꜝᴟԜᴡꜝᴟᴦͼⱨᴑᴣᴒᴟᴠᴒͼⱬᴣᴒꜜᴡᴠ᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅⅍᷉
⅍᷅᷈⅍᷿᷅
ϸᴒꜞꜝᴟᴡ꞉ꜜⱲͼⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟͼᴀԜⱱᴒᴡᴦͼ꜡ԝᴠᴒᴟᴣԜᴡ꞉ꜝꜜᴠͼᴡꜝͼᴡⱳᴒͼᴀꜞꜝꜜᴠꜝᴟ᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅⅍᷊
⅍᷅᷈⅍᷿᷅᷅᷈
ϸᴒꜞꜝᴟᴡ꞉ꜜⱲͼ꜠ꜝꜜ᷄ᴀᴒᴟ꞉ꜝᴢᴠͼⱨᴑᴣᴒᴟᴠᴒͼⱬᴣᴒꜜᴡᴠ᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅⅍᷊
⅍᷅᷈⅍᷿᷅᷅᷉
ϸᴒꜞꜝᴟᴡ꞉ꜜⱲͼ͟ᴟᴒⱲꜜԜꜜᴐ꞉ᴒᴠ᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅⅍᷊
⅍᷅᷈⅍᷿᷊᷅᷅
ᴀԜⱱᴒᴡᴦͼ꜡ԝᴠᴒᴟᴣԜᴡ꞉ꜝꜜᴠͼϸᴒꜟᴢ꞉ᴟ꞉ꜜⱲͼⱬᴥꜞᴒᴑ꞉ᴡᴒᴑͼϸᴒꜞꜝᴟᴡ꞉ꜜⱲͼԝᴦͼᴡⱳᴒͼ
ⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟͼᴡꜝᴡⱳᴒͼᴀꜞꜝꜜᴠꜝᴟ᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅⅍᷊
⅍᷅᷈⅍᷿᷅᷅᷾
ⱬᴥꜞᴒᴑ꞉ᴡᴒᴑͼϸᴒꜞꜝᴟᴡ꞉ꜜⱲͼԝᴦͼᴡⱳᴒͼᴀꜞꜝꜜᴠꜝᴟͼᴡꜝͼԜͼϸᴒⱲᴢꞌԜᴡꜝᴟᴦͼⱶᴒԜꞌᴡⱳͼ
ⱨᴢᴡⱳꜝᴟ꞉ᴡᴦ᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅⅍᷾
⅍᷅᷈⅍᷿᷿᷅᷅
ᴀԜⱱᴒᴡᴦͼⱪꜝꜜᴡԜᴐᴡͼⱷꜜⱱꜝᴟꜛԜᴡ꞉ꜝꜜ᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅⅍᷾
⅍᷅᷈⅍᷿᷅᷅⅍
ᴀԜⱱᴒᴡᴦͼ꜠ꜝᴡ꞉ⱱ꞉ᴐԜᴡ꞉ꜝꜜᴠͼԝᴦͼᴡⱳᴒͼᴀꜞꜝꜜᴠꜝᴟͼᴡꜝͼᴡⱳᴒͼⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟ᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅⅍᷾
⅍᷅᷈⅍᷿᷅᷅ⅎ
ᴂꜜԝꞌ꞉ꜜᴑ꞉ꜜⱲͼԜͼᴀᴢԝ꞊ᴒᴐᴡᶳᴠͼᴁᴟᴒԜᴡꜛᴒꜜᴡͼᴑᴢᴟ꞉ꜜⱲͼᴡⱳᴒͼᴁᴟ꞉Ԝꞌ᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅⅍᷾
⅍᷅᷈ⅎ
ᴀᴢԝ꞊ᴒᴐᴡͼᴄ꞉ᴡⱳᴑᴟԜᴤԜꞌ᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅⅍᷾

Ⱬᴅ᷄᷉Ⱡ᷊᷇
ⱪꞌ꞉ꜜ꞉ᴐԜꞌͼᴁᴟ꞉Ԝꞌͼ͟ᴟꜝᴡꜝᴐꜝꞌⱡͼⱫᴅ᷄᷉Ⱡ᷊᷊᷇᷄᷇
ⱨꜛᴒꜜᴑꜛᴒꜜᴡͼ᷊᷅᷇ͼⱴ꞉ꜜԜꞌⱡͼ᷇ⱠͼꜗԜꜜᴢԜᴟᴦ᷉᷇᷈ⅎ
ⱪꜝꜜⱱ꞉ᴑᴒꜜᴡ꞉Ԝꞌ
͟ԜⱲᴒͼ᷿᷉
ⱫᴦԜᴥͼⱪꜝᴟꜞ᷅
⅍᷅᷈˲
ⱨꜞꜞᴟꜝꜞᴟ꞉ԜᴡᴒꜜᴒᴠᴠͼꜝⱱͼꜚᴒԜᴠᴢᴟᴒꜛᴒꜜᴡᴠ᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅⅍᷿
ⅎ
ᴀᴁᴂⱫᴆͼⱨⱪᴁⱷᴃⱷᴁⱷⱬᴀ᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅⅍⅍
ⅎ᷅᷈
ᴀᴐᴟᴒᴒꜜ꞉ꜜⱲ᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅⅍⅍
ⅎ᷅᷉
ϸᴢꜜ᷄꞉ꜜͼ͟ᴒᴟ꞉ꜝᴑ᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅⅍⅍
ⅎ᷊᷅
ᴀᴡԜᴟᴡͼꜝⱱͼᴁᴟᴒԜᴡꜛᴒꜜᴡͼ͟ᴒᴟ꞉ꜝᴑⱡͼᴃ꞉ᴠ꞉ᴡͼ᷈ԓͼⱫꜝᴠᴒͼ᷈ͼӿⱫԜᴦͼ᷇Ԑ ᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅⅍ⅎ
ⅎ᷅᷾
ᴀ꞉ᴡᴒͼⱪꜝꜜᴡԜᴐᴡͼᴤ꞉ᴡⱳͼᴡⱳᴒͼᴀᴢԝ꞊ᴒᴐᴡ᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅⅍˲
ⅎ᷿᷅
ⱪꜝꜜᴡ꞉ꜜᴢԜᴡ꞉ꜝꜜͼꜝⱱͼᴁᴟᴒԜᴡꜛᴒꜜᴡͼ͟ᴒᴟ꞉ꜝᴑⱡͼᴃ꞉ᴠ꞉ᴡͼ᷉ԓͼⱫꜝᴠᴒͼ᷉ͼӿⱫԜᴦͼ᷈᷾ᶐ᷊ⱫԜᴦᴠԐ᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅⅍˲
ⅎ᷅⅍
ⱪꜝꜜᴡ꞉ꜜᴢԜᴡ꞉ꜝꜜͼꜝⱱͼᴁᴟᴒԜᴡꜛᴒꜜᴡͼ͟ᴒᴟ꞉ꜝᴑⱡͼᴃ꞉ᴠ꞉ᴡͼ᷊ԓͼⱫꜝᴠᴒͼ᷊ͼӿⱫԜᴦͼ᷉˲ᶐ᷊ⱫԜᴦᴠԐ᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅⅍Ⱡ
ⅎ᷅ⅎ
ⱪꜝꜜᴡ꞉ꜜᴢԜᴡ꞉ꜝꜜͼꜝⱱͼᴁᴟᴒԜᴡꜛᴒꜜᴡͼ͟ᴒᴟ꞉ꜝᴑⱡͼᴃ꞉ᴠ꞉ᴡͼ᷾ԓͼⱫꜝᴠᴒͼ᷾ͼӿⱫԜᴦͼ᷾᷉ͼᶐ᷊ⱫԜᴦᴠԐ᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅⅍Ⱡ
ⅎ᷅˲
ⱪꜝꜜᴡ꞉ꜜᴢԜᴡ꞉ꜝꜜͼꜝⱱͼᴁᴟᴒԜᴡꜛᴒꜜᴡͼ͟ᴒᴟ꞉ꜝᴑⱡͼᴃ꞉ᴠ꞉ᴡͼ᷿ԓͼⱫꜝᴠᴒͼ᷿ͼӿⱫԜᴦͼ᷿⅍ᶐ᷊ⱫԜᴦᴠԐ᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅ⅎ᷇
ⅎ᷅Ⱡ
ⱪꜝꜜᴡ꞉ꜜᴢԜᴡ꞉ꜝꜜͼꜝⱱͼᴁᴟᴒԜᴡꜛᴒꜜᴡͼ͟ᴒᴟ꞉ꜝᴑⱡͼᴃ꞉ᴠ꞉ᴡᴠͼ⅍ͼԜꜜᴑͼⅎԓͼⱫꜝᴠᴒᴠͼ⅍ͼԜꜜᴑͼⅎͼͼ
ӿⱫԜᴦᴠⅎ᷇Ԝꜜᴑ˲᷾ԓͼⱨꞌꞌͼᶐ᷊ⱫԜᴦᴠԐ ᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅ⅎ᷈
ⅎ᷅᷈᷇
ⱪꜝꜜᴡ꞉ꜜᴢԜᴡ꞉ꜝꜜͼꜝⱱͼᴁᴟᴒԜᴡꜛᴒꜜᴡͼ͟ᴒᴟ꞉ꜝᴑⱡͼᴃ꞉ᴠ꞉ᴡͼ˲ԓͼⱫꜝᴠᴒͼ˲ͼӿⱫԜᴦͼⱠ˲ᶐ᷊ⱫԜᴦᴠԐ᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅ⅎ᷉
ⅎ᷅᷈᷈
ⱪꜝꜜᴡ꞉ꜜᴢԜᴡ꞉ꜝꜜͼꜝⱱͼᴁᴟᴒԜᴡꜛᴒꜜᴡͼ͟ᴒᴟ꞉ꜝᴑⱡͼᴃ꞉ᴠ꞉ᴡᴠͼⱠͼԜꜜᴑͼ᷈᷇ԓͼⱫꜝᴠᴒᴠͼⱠͼԜꜜᴑͼ᷈᷇ͼ ӿⱫԜᴦᴠͼ᷈᷈᷉ͼ
Ԝꜜᴑͼ᷈᷉⅍ԓͼⱨꞌꞌͼᶐ᷊ⱫԜᴦᴠԐ᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅ⅎ᷊
ⅎ᷅᷈᷉
ⱪꜝꜜᴡ꞉ꜜᴢԜᴡ꞉ꜝꜜͼꜝⱱͼᴁᴟᴒԜᴡꜛᴒꜜᴡͼ͟ᴒᴟ꞉ꜝᴑⱡͼᴃ꞉ᴠ꞉ᴡͼ᷈᷈ԓͼⱫꜝᴠᴒͼ᷈᷈ͼӿⱫԜᴦͼ᷈᷾᷇ᶐ᷊ⱫԜᴦᴠԐ᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅ⅎ᷊
ⅎ᷊᷅᷈
ⱪꜝꜜᴡ꞉ꜜᴢԜᴡ꞉ꜝꜜͼꜝⱱͼᴁᴟᴒԜᴡꜛᴒꜜᴡͼ͟ᴒᴟ꞉ꜝᴑͼӿⱫԜᴦͼ᷈᷾᷾ᶐ᷈ⱫԜᴦԐ ᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅ⅎ᷾
ⅎ᷅᷈᷾
ⱪꜝꜜᴡ꞉ꜜᴢԜᴡ꞉ꜝꜜͼꜝⱱͼᴁᴟᴒԜᴡꜛᴒꜜᴡͼ͟ᴒᴟ꞉ꜝᴑⱡͼᴃ꞉ᴠ꞉ᴡᴠͼ᷈᷉ͼԜꜜᴑͼ᷊᷈ԓͼⱫꜝᴠᴒᴠͼ᷈᷉ͼԜꜜᴑͼ᷊᷈ͼӿⱫԜᴦᴠͼ᷿᷈᷾ͼ
Ԝꜜᴑͼ᷈⅍˲ԓͼⱨꞌꞌͼᶐ᷊ⱫԜᴦᴠԐ᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅ⅎ᷾
ⅎ᷿᷅᷈
ⱪꜝꜛꜞꞌᴒᴡ꞉ꜝꜜͼꜝⱱͼᴁᴟᴒԜᴡꜛᴒꜜᴡͼ͟ᴒᴟ꞉ꜝᴑⱡͼᴃ꞉ᴠ꞉ᴡͼ᷈᷾ԓͼⱫԜᴦͼ᷈˲᷉ᶐ᷊ⱫԜᴦᴠ᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅ⅎ᷿
ⅎ᷅᷈⅍
ⱴꜝꞌꞌꜝᴤ᷄ᴢꜞͼ͟ᴒᴟ꞉ꜝᴑͼӿᴀᴢԝ꞊ᴒᴐᴡᴠͼ꜠ꜝᴡͼⱪꜝꜜᴡ꞉ꜜᴢ꞉ꜜⱲͼ꞉ꜜͼ꜡ꜞᴒꜜ᷄ꜙԜԝᴒꞌͼⱬᴥᴡᴒꜜᴠ꞉ꜝꜜͼᴀᴡᴢᴑᴦԐⱡͼ
ᴃ꞉ᴠ꞉ᴡͼ᷿᷈ԓͼⱫԜᴦͼ᷉᷈᷇ͼᶐ᷊ⱫԜᴦᴠ᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅ⅎ⅍
ⅎ᷅᷈ⅎ
ⱴ꞉ꜜԜꞌͼⱴꜝꞌꞌꜝᴤ᷄ᴢꜞͼᴃ꞉ᴠ꞉ᴡͼӿᴀᴢԝ꞊ᴒᴐᴡᴠͼ꜠ꜝᴡͼⱪꜝꜜᴡ꞉ꜜᴢ꞉ꜜⱲͼ꞉ꜜͼ꜡ꜞᴒꜜ᷄ꜙԜԝᴒꞌͼⱬᴥᴡᴒꜜᴠ꞉ꜝꜜͼᴀᴡᴢᴑᴦԐⱡͼ
ᴃ꞉ᴠ꞉ᴡͼ᷈⅍ԓͼⱫԜᴦͼ᷊᷉˲ᶐ᷊ⱫԜᴦᴠ᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅ⅎ⅍
ⅎ᷅᷈˲
ⱬԜᴟꞌᴦͼᴁᴒᴟꜛ꞉ꜜԜᴡ꞉ꜝꜜͼӿⱬᴁԐ᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅ⅎ⅍
˲
Ϸᴂⱨꜙⱷᴁᴆͼⱪ꜡꜠ᴁϸ꜡ꜙͼⱨ꜠Ⱬͼⱨᴀᴀᴂϸⱨ꜠ⱪⱬ᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅ⅎⅎ
Ⱡ
Ⱬⱨᴁⱨͼⱨ꜠ⱨꜙᴆᴀⱷᴀͼ᷆ͼᴀᴁⱨᴁⱷᴀᴁⱷⱪⱨꜙͼꜚⱬᴁⱶ꜡Ⱬᴀ᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅ⅎ˲
Ⱡ᷅᷈
ⱵᴒꜜᴒᴟԜꞌͼⱪꜝꜜᴠ꞉ᴑᴒᴟԜᴡ꞉ꜝꜜᴠ᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅ⅎ˲
Ⱡ᷅᷉
ᴀԜꜛꜞꞌᴒͼᴀ꞉ᴧᴒͼⱫᴒᴡᴒᴟꜛ꞉ꜜԜᴡ꞉ꜝꜜ᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅ⅎ˲
Ⱡ᷊᷅
ꜚᴒᴡⱳꜝᴑͼꜝⱱͼⱨᴠᴠ꞉Ⱳꜜ꞉ꜜⱲͼᴀᴡᴢᴑᴦͼᴀᴢԝ꞊ᴒᴐᴡᴠͼᴡꜝͼᴁᴟᴒԜᴡꜛᴒꜜᴡͼⱵᴟꜝᴢꜞᴠ᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅ⅎ˲
Ⱡ᷅᷾
ⱨꜜԜꞌᴦᴠ꞉ᴠͼ͟ꜝꜞᴢꞌԜᴡ꞉ꜝꜜᴠ᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅ⅎⱠ
Ⱡ᷿᷅
ⱨꜜԜꞌᴦᴠ꞉ᴠͼꜝⱱͼⱫ꞉ᴠꜞꜝᴠ꞉ᴡ꞉ꜝꜜ᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅ⅎⱠ
Ⱡ᷅⅍
ⱫᴒꜛꜝⱲᴟԜꜞⱳ꞉ᴐᴠͼԜꜜᴑͼⱩԜᴠᴒꞌ꞉ꜜᴒͼⱪⱳԜᴟԜᴐᴡᴒᴟ꞉ᴠᴡ꞉ᴐᴠͼⱨꜜԜꞌᴦᴠᴒᴠ᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅ⅎⱠ
Ⱡ᷅ⅎ
ᴁᴟᴒԜᴡꜛᴒꜜᴡͼⱪꜝꜛꜞꞌ꞉ԜꜜᴐᴒͼԜꜜᴑͼⱬᴥᴡᴒꜜᴡͼꜝⱱͼⱬᴥꜞꜝᴠᴢᴟᴒ᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅ⅎⱠ
Ⱡ᷅˲
ⱨꜜԜꞌᴦᴠ꞉ᴠͼꜝⱱͼ͟ᴟ꞉ꜛԜᴟᴦͼԜꜜᴑͼᴀᴒᴐꜝꜜᴑԜᴟᴦͼⱬⱱⱱ꞉ᴐԜᴐᴦͼⱬꜜᴑꜞꜝ꞉ꜜᴡᴠ᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅ⅎⱠ
Ⱡ᷅˲᷅᷈
͟ᴟ꞉ꜛԜᴟᴦͼⱬⱱⱱ꞉ᴐԜᴐᴦͼⱬꜜᴑꜞꜝ꞉ꜜᴡ᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅ⅎⱠ
Ⱡ᷅˲᷅᷉
ᴀᴒᴐꜝꜜᴑԜᴟᴦͼⱬⱱⱱ꞉ᴐԜᴐᴦͼⱬꜜᴑꜞꜝ꞉ꜜᴡᴠ᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅˲᷇
Ⱡ᷅˲᷊᷅
ⱬᴥꜞꞌꜝᴟԜᴡꜝᴟᴦͼⱬⱱⱱ꞉ᴐԜᴐᴦͼⱬꜜᴑꜞꜝ꞉ꜜᴡᴠ᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅˲᷈
Ⱡ᷅Ⱡ
ⱨꜜԜꞌᴦᴠ꞉ᴠͼꜝⱱͼ͟ⱳԜᴟꜛԜᴐꜝꞋ꞉ꜜᴒᴡ꞉ᴐͼԜꜜᴑͼ͟ⱳԜᴟꜛԜᴐꜝᴑᴦꜜԜꜛ꞉ᴐͼⱬꜜᴑꜞꜝ꞉ꜜᴡᴠ᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅˲᷈

Ⱬᴅ᷄᷉Ⱡ᷊᷇
ⱪꞌ꞉ꜜ꞉ᴐԜꞌͼᴁᴟ꞉Ԝꞌͼ͟ᴟꜝᴡꜝᴐꜝꞌⱡͼⱫᴅ᷄᷉Ⱡ᷊᷊᷇᷄᷇
ⱨꜛᴒꜜᴑꜛᴒꜜᴡͼ᷊᷅᷇ͼⱴ꞉ꜜԜꞌⱡͼ᷇ⱠͼꜗԜꜜᴢԜᴟᴦ᷉᷇᷈ⅎ
ⱪꜝꜜⱱ꞉ᴑᴒꜜᴡ꞉Ԝꞌ
͟ԜⱲᴒͼ᷉⅍
ⱫᴦԜᴥͼⱪꜝᴟꜞ᷅
Ⱡ᷅Ⱡ᷅᷈
͟ⱳԜᴟꜛԜᴐꜝꞋ꞉ꜜᴒᴡ꞉ᴐͼⱨᴠᴠᴒᴠᴠꜛᴒꜜᴡᴠⱡ᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅˲᷈
Ⱡ᷅Ⱡ᷅᷉
͟ⱳԜᴟꜛԜᴐꜝᴑᴦꜜԜꜛ꞉ᴐͼⱨᴠᴠᴒᴠᴠꜛᴒꜜᴡᴠⱡ᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅˲᷈
Ⱡ᷅Ⱡ᷊᷅
ⱷꜛꜛᴢꜜꜝⱲᴒꜜ꞉ᴐ꞉ᴡᴦͼⱨᴠᴠᴒᴠᴠꜛᴒꜜᴡᴠⱡ᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅˲᷉
Ⱡ᷅Ⱡ᷅᷾
ⱪ᷈᷄ⱷ꜠ⱶͼԜꜜᴑͼⱪ᷾ͼⱨᴠᴠᴒᴠᴠꜛᴒꜜᴡᴠⱡ᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅˲᷉
Ⱡ᷅᷈᷇
ᴀԜⱱᴒᴡᴦͼⱨꜜԜꞌᴦᴠ꞉ᴠ᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅˲᷉
Ⱡ᷅᷈᷈
ⱨꜜԜꞌᴦᴠ꞉ᴠͼꜝⱱͼϷᴢԜꞌ꞉ᴡᴦͼꜝⱱͼꜙ꞉ⱱᴒͼⱨᴠᴠᴒᴠᴠꜛᴒꜜᴡᴠ᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅˲᷊
Ⱡ᷅᷈᷉
ᴀᴡԜᴡ꞉ᴠᴡ꞉ᴐԜꞌ᷆ⱨꜜԜꞌᴦᴡ꞉ᴐͼⱷᴠᴠᴢᴒᴠ᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅˲᷊
Ⱡ᷅᷈᷉᷅᷈
ⱨᴑ꞊ᴢᴠᴡꜛᴒꜜᴡͼⱱꜝᴟͼⱪꜝᴣԜᴟ꞉Ԝᴡᴒᴠ᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅˲᷊
Ⱡ᷅᷈᷉᷅᷉
ⱶԜꜜᴑꞌ꞉ꜜⱲͼꜝⱱͼⱫᴟꜝꜞꜝᴢᴡᴠͼꜝᴟͼꜚ꞉ᴠᴠ꞉ꜜⱲͼⱫԜᴡԜ᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅˲᷊
Ⱡ᷊᷅᷈᷉᷅
ⱷꜜᴡᴒᴟ꞉ꜛͼⱨꜜԜꞌᴦᴠ꞉ᴠͼԜꜜᴑͼⱫԜᴡԜͼꜚꜝꜜ꞉ᴡꜝᴟ꞉ꜜⱲ᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅˲᷊
Ⱡ᷅᷈᷉᷅᷾
ꜚᴢꞌᴡ꞉ᴐᴒꜜᴡᴒᴟͼᴀᴡᴢᴑ꞉ᴒᴠ᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅˲᷊
Ⱡ᷿᷅᷈᷉᷅
ꜚᴢꞌᴡ꞉ꜞꞌᴒͼⱪꜝꜛꜞԜᴟ꞉ᴠꜝꜜᴠ᷆ꜚᴢꞌᴡ꞉ꜞꞌ꞉ᴐ꞉ᴡᴦ᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅˲᷊
Ⱡ᷅᷈᷉᷅⅍
ᴀᴒꜜᴠ꞉ᴡ꞉ᴣ꞉ᴡᴦͼⱨꜜԜꞌᴦᴠᴒᴠ᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅˲᷾
᷈᷇
ᴀᴁᴂⱫᴆͼⱨⱫꜚⱷ꜠ⱷᴀᴁϸⱨᴁⱷᴃⱬᴀᴁϸᴂⱪᴁᴂϸⱬ᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅˲᷿
᷈᷇᷅᷈
ⱷꜜᴠᴡ꞉ᴡᴢᴡ꞉ꜝꜜԜꞌͼϸᴒᴣ꞉ᴒᴤͼⱩꜝԜᴟᴑ᷆ϸᴒᴠᴒԜᴟᴐⱳͼⱬᴡⱳ꞉ᴐᴠͼⱩꜝԜᴟᴑ᷆ⱷꜜᴑᴒꜞᴒꜜᴑᴒꜜᴡͼⱬᴡⱳ꞉ᴐᴠͼ
ⱪꜝꜛꜛ꞉ᴡᴡᴒᴒ᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅˲᷿
᷈᷇᷅᷉
ⱬᴡⱳ꞉ᴐԜꞌͼⱪꜝꜜᴑᴢᴐᴡͼꜝⱱͼᴡⱳᴒͼᴀᴡᴢᴑᴦ᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅˲⅍
᷊᷈᷇᷅
ᴀᴢԝ꞊ᴒᴐᴡͼⱷꜜⱱꜝᴟꜛԜᴡ꞉ꜝꜜͼԜꜜᴑͼⱪꜝꜜᴠᴒꜜᴡ᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅˲⅍
᷈᷇᷅᷾
ᴀᴢԝ꞊ᴒᴐᴡͼⱪꜝꜜⱱ꞉ᴑᴒꜜᴡ꞉Ԝꞌ꞉ᴡᴦ᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅˲⅍
᷿᷈᷇᷅
ᴀᴡᴢᴑᴦͼꜚꜝꜜ꞉ᴡꜝᴟ꞉ꜜⱲ᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅˲⅍
᷈᷇᷅⅍
ⱪԜᴠᴒͼϸᴒꜞꜝᴟᴡͼⱴꜝᴟꜛᴠͼԜꜜᴑͼᴀᴡᴢᴑᴦͼϸᴒᴐꜝᴟᴑᴠ᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅˲ⅎ
᷈᷇᷅ⅎ
ⱫԜᴡԜͼᴀԜⱱᴒᴡᴦͼꜚꜝꜜ꞉ᴡꜝᴟ꞉ꜜⱲͼⱩꜝԜᴟᴑ᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅˲ⅎ
᷈᷇᷅˲
͟ᴟꜝᴡꜝᴐꜝꞌͼᴃ꞉ꜝꞌԜᴡ꞉ꜝꜜᴠ᷆Ⱬᴒᴣ꞉Ԝᴡ꞉ꜝꜜᴠ᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅˲˲
᷈᷇᷅Ⱡ
͟ᴟᴒꜛԜᴡᴢᴟᴒͼⱪꞌꜝᴠᴢᴟᴒͼꜝⱱͼᴡⱳᴒͼᴀᴡᴢᴑᴦ᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅˲˲
᷈᷇᷅᷈᷇ⱨᴐᴐᴒᴠᴠͼᴡꜝͼᴀꜝᴢᴟᴐᴒͼⱫꜝᴐᴢꜛᴒꜜᴡԜᴡ꞉ꜝꜜͼԜꜜᴑͼ꜡ꜜ᷄ᴀ꞉ᴡᴒͼⱨᴢᴑ꞉ᴡᴠ᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅˲˲
᷈᷇᷅᷈᷈ⱫԜᴡԜͼⱵᴒꜜᴒᴟԜᴡ꞉ꜝꜜͼԜꜜᴑͼⱨꜜԜꞌᴦᴠ꞉ᴠ᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅˲Ⱡ
᷈᷇᷅᷈᷉ⱫԜᴡԜͼⱶԜꜜᴑꞌ꞉ꜜⱲͼⱪꜝꜜᴠ꞉ᴑᴒᴟԜᴡ꞉ꜝꜜᴠ᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅˲Ⱡ
᷊᷈᷇᷅᷈ϸᴒᴡᴒꜜᴡ꞉ꜝꜜͼꜝⱱͼⱫԜᴡԜ᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅˲Ⱡ
᷈᷇᷅᷈᷾ⱴ꞉ꜜԜꜜᴐ꞉ԜꞌͼⱫ꞉ᴠᴐꞌꜝᴠᴢᴟᴒ᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅Ⱡ᷇
᷿᷈᷇᷅᷈͟ᴢԝꞌ꞉ᴐԜᴡ꞉ꜝꜜͼԜꜜᴑͼⱫ꞉ᴠᴐꞌꜝᴠᴢᴟᴒͼ͟ꜝꞌ꞉ᴐᴦ᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅Ⱡ᷇
᷈᷈
ϸⱬⱴⱬϸⱬ꜠ⱪⱬͼꜙⱷᴀᴁ᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅Ⱡ᷈
᷈᷉
ⱨ͟͟ⱬ꜠Ⱬⱷⱪⱬᴀ᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅Ⱡ᷊
LIST OF IN-TEXT TABLES
ᴁԜԝꞌᴒͼ᷈᷅
ᴀᴡᴢᴑᴦͼⱨᴐᴡ꞉ᴣ꞉ᴡ꞉ᴒᴠͼᴀᴐⱳᴒᴑᴢꞌᴒ᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷈Ⱡ
ᴁԜԝꞌᴒ᷉᷅
ᴁᴟᴒԜᴡꜛᴒꜜᴡͼ͟ᴒᴟ꞉ꜝᴑͼⱫꜝᴠ꞉ꜜⱲͼᴀᴐⱳᴒᴑᴢꞌᴒ᷊᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅Ⱡ
ᴁԜԝꞌᴒ᷊᷅
ᴀᴡᴢᴑᴦͼⱨᴑꜛ꞉ꜜ꞉ᴠᴡᴟԜᴡ꞉ᴣᴒͼᴀᴡᴟᴢᴐᴡᴢᴟᴒ᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅˲᷿

Ⱬᴅ᷄᷉Ⱡ᷊᷇
ⱪꞌ꞉ꜜ꞉ᴐԜꞌͼᴁᴟ꞉Ԝꞌͼ͟ᴟꜝᴡꜝᴐꜝꞌⱡͼⱫᴅ᷄᷉Ⱡ᷊᷊᷇᷄᷇
ⱨꜛᴒꜜᴑꜛᴒꜜᴡͼ᷊᷅᷇ͼⱴ꞉ꜜԜꞌⱡͼ᷇ⱠͼꜗԜꜜᴢԜᴟᴦ᷉᷇᷈ⅎ
ⱪꜝꜜⱱ꞉ᴑᴒꜜᴡ꞉Ԝꞌ
͟ԜⱲᴒͼ᷉ⅎ
ⱫᴦԜᴥͼⱪꜝᴟꜞ᷅
LIST OF IN-TEXT FIGURES
ⱴ꞉Ⱳᴢᴟᴒ᷈᷅
꜡ᴣᴒᴟᴣ꞉ᴒᴤͼꜝⱱͼᴡⱳᴒͼᴀᴡᴢᴑᴦͼⱫᴒᴠ꞉Ⱳꜜ᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷾᷇
LIST OF APPENDICES
ⱨꜞꜞᴒꜜᴑ꞉ᴥͼ᷈
͟ᴟꜝᴡꜝᴐꜝꞌͼⱶ꞉ᴠᴡꜝᴟᴦ᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅Ⱡ᷾
ⱨꜞꜞᴒꜜᴑ꞉ᴥͼ᷉
꜠Ԝᴡ꞉ꜝꜜԜꞌͼⱷꜜᴠᴡ꞉ᴡᴢᴡᴒͼꜝⱱͼⱨꞌꞌᴒᴟⱲᴦͼԜꜜᴑͼⱷꜜⱱᴒᴐᴡ꞉ꜝᴢᴠͼⱫ꞉ᴠᴒԜᴠᴒᴠԓͼⱫ꞉ᴣ꞉ᴠ꞉ꜝꜜͼꜝⱱͼ
ꜚ꞉ᴐᴟꜝԝ꞉ꜝꞌꜝⱲᴦͼԜꜜᴑͼⱷꜜⱱᴒᴐᴡ꞉ꜝᴢᴠͼⱫ꞉ᴠᴒԜᴠᴒᴠͼӿⱫꜚⱷⱫԐͼⱨᴑᴢꞌᴡͼᴁꜝᴥ꞉ᴐ꞉ᴡᴦͼᴁԜԝꞌᴒͼӿꜚꜝᴑ꞉ⱱ꞉ᴒᴑԐͼͼͼͼ
ӿᴂᴀ꜠Ԝᴡ꞉ꜝꜜԜꞌͼⱷꜜᴠᴡ꞉ᴡᴢᴡᴒᴠͼꜝⱱͼⱶᴒԜꞌᴡⱳⱢͼ꜠Ԝᴡ꞉ꜝꜜԜꞌͼⱷꜜᴠᴡ꞉ᴡᴢᴡᴒͼꜝⱱͼⱨꞌꞌᴒᴟⱲᴦͼԜꜜᴑͼⱷꜜⱱᴒᴐᴡ꞉ꜝᴢᴠͼ
Ⱬ꞉ᴠᴒԜᴠᴒᴠԐᶨᶨᶨ᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷈᷇᷾
ⱨꜞꜞᴒꜜᴑ꞉ᴥͼ᷊
꜠Ԝᴡ꞉ꜝꜜԜꞌͼⱷꜜᴠᴡ꞉ᴡᴢᴡᴒͼꜝⱱͼⱨꞌꞌᴒᴟⱲᴦͼԜꜜᴑͼⱷꜜⱱᴒᴐᴡ꞉ꜝᴢᴠͼⱫ꞉ᴠᴒԜᴠᴒᴠԓͼⱫ꞉ᴣ꞉ᴠ꞉ꜝꜜͼꜝⱱͼ
ꜚ꞉ᴐᴟꜝԝ꞉ꜝꞌꜝⱲᴦͼԜꜜᴑͼⱷꜜⱱᴒᴐᴡ꞉ꜝᴢᴠͼⱫ꞉ᴠᴒԜᴠᴒᴠͼӿⱫꜚⱷⱫԐͼ͟ᴒᴑ꞉Ԝᴡᴟ꞉ᴐͼᴁꜝᴥ꞉ᴐ꞉ᴡᴦͼᴁԜԝꞌᴒᴠͼӿꜚꜝᴑ꞉ⱱ꞉ᴒᴑԐ
ӿᴂᴀͼ꜠Ԝᴡ꞉ꜝꜜԜꞌͼⱷꜜᴠᴡ꞉ᴡᴢᴡᴒᴠͼꜝⱱͼⱶᴒԜꞌᴡⱳⱢͼ꜠Ԝᴡ꞉ꜝꜜԜꞌͼⱷꜜᴠᴡ꞉ᴡᴢᴡᴒͼꜝⱱͼⱨꞌꞌᴒᴟⱲᴦͼԜꜜᴑͼⱷꜜⱱᴒᴐᴡ꞉ꜝᴢᴠ
Ⱬ꞉ᴠᴒԜᴠᴒᴠᶨᶨᶨ᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷅᷈᷈ⅎ
ⱨꜞꜞᴒꜜᴑ꞉ᴥͼ᷾
ⱶⱨⱬͼⱨᴡᴡԜᴐꞋͼⱨᴠᴠᴒᴠᴠꜛᴒꜜᴡͼԜꜜᴑͼϸᴒꜞꜝᴟᴡ꞉ꜜⱲͼ͟ᴟꜝᴐᴒᴑᴢᴟᴒᴠͼӿⱶⱨⱨϸ͟Ԑ᷊᷅᷅᷅᷅᷅᷅᷈᷈

Ⱬᴅ᷄᷉Ⱡ᷊᷇
ⱪꞌ꞉ꜜ꞉ᴐԜꞌͼᴁᴟ꞉Ԝꞌͼ͟ᴟꜝᴡꜝᴐꜝꞌⱡͼⱫᴅ᷄᷉Ⱡ᷊᷊᷇᷄᷇
ⱨꜛᴒꜜᴑꜛᴒꜜᴡͼ᷊᷅᷇ͼⱴ꞉ꜜԜꞌⱡͼ᷇ⱠͼꜗԜꜜᴢԜᴟᴦ᷉᷇᷈ⅎ
ⱪꜝꜜⱱ꞉ᴑᴒꜜᴡ꞉Ԝꞌ
͟ԜⱲᴒͼ᷉˲
ⱫᴦԜᴥͼⱪꜝᴟꜞ᷅
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS
ⱨⱨⱬ
ⱨᴐꜟᴢ꞉ᴟᴒᴑͼԜꜜⱲ꞉ꜝᴒᴑᴒꜛԜ
ⱨⱪⱬ
ⱨꜜⱲ꞉ꜝᴡᴒꜜᴠ꞉ꜜͼᴐꜝꜜᴣᴒᴟᴡ꞉ꜜⱲͼᴒꜜᴧᴦꜛᴒ
ⱨⱬ
ⱨᴑᴣᴒᴟᴠᴒͼᴒᴣᴒꜜᴡ
ⱨⱬᴀⱷ
ⱨᴑᴣᴒᴟᴠᴒͼⱬᴣᴒꜜᴡͼꜝⱱͼᴀꜞᴒᴐ꞉Ԝꞌͼⱷꜜᴡᴒᴟᴒᴠᴡ
ⱨⱬ᷄Ϸꜝꜙ
ⱨꜜⱲ꞉ꜝᴒᴑᴒꜛԜ᷄ϷᴢԜꞌ꞉ᴡᴦͼꜝⱱͼꜙ꞉ⱱᴒͼϷᴢᴒᴠᴡ꞉ꜝꜜꜜԜ꞉ᴟᴒ
ⱨꜙᴁ
ⱨꞌԜꜜ꞉ꜜᴒͼԜꜛ꞉ꜜꜝᴡᴟԜꜜᴠⱱᴒᴟԜᴠᴒ
ⱨ꜠꜡ᴃⱨ
ⱨꜜԜꞌᴦᴠ꞉ᴠͼꜝⱱͼᴣԜᴟ꞉Ԝꜜᴐᴒ
Ԝ͟ᴁᴁ
ⱨᴐᴡ꞉ᴣԜᴡᴒᴑͼꜞԜᴟᴡ꞉ԜꞌͼᴡⱳᴟꜝꜛԝꜝꜞꞌԜᴠᴡ꞉ꜜͼᴡ꞉ꜛᴒ
ⱨᴀᴁ
ⱨᴠꜞԜᴟᴡԜᴡᴒͼԜꜛ꞉ꜜꜝᴡᴟԜꜜᴠⱱᴒᴟԜᴠᴒ
ⱨᴂⱪ
ⱨᴟᴒԜͼᴢꜜᴑᴒᴟͼᴡⱳᴒͼꜞꞌԜᴠꜛԜ ᴐꜝꜜᴐᴒꜜᴡᴟԜᴡ꞉ꜝꜜ᷄ᴡ꞉ꜛᴒͼᴐᴢᴟᴣᴒ
ⱨᴂⱪ᷇᷄ᴡ
ⱨᴂⱪͼⱱᴟꜝꜛͼᴡ꞉ꜛᴒͼᴧᴒᴟꜝͼᴡꜝͼᴡⱳᴒͼꞌԜᴠᴡͼꜟᴢԜꜜᴡ꞉ⱱ꞉ԜԝꞌᴒͼᴐꜝꜜᴐᴒꜜᴡᴟԜᴡ꞉ꜝꜜͼ꞉ꜜͼꜞꞌԜᴠꜛԜͼԜᴡͼ
ᴡ꞉ꜛᴒͼᴡ
ⱨᴂⱪ᷇᷄ᶏ
ⱨᴂⱪͼⱱᴟꜝꜛͼᴡ꞉ꜛᴒͼ᷇ͼᴡꜝͼ꞉ꜜⱱ꞉ꜜ꞉ᴡᴦ
ⱨᴂⱪꞌԜᴠᴡ
ⱨᴂⱪͼⱱᴟꜝꜛͼᴡ꞉ꜛᴒͼ᷇ͼᴡꜝͼᴡⱳᴒͼꞌԜᴠᴡͼꜛᴒԜᴠᴢᴟԜԝꞌᴒͼᴐꜝꜜᴐᴒꜜᴡᴟԜᴡ꞉ꜝꜜ
Ⱪꜙⱨ
Ⱪ꞉ꜝꞌꜝⱲ꞉ᴐᴠͼꜙ꞉ᴐᴒꜜᴠᴒͼⱨꜞꜞꞌ꞉ᴐԜᴡ꞉ꜝꜜ
Ⱪꜚⱷ
ⱩꜝᴑᴦͼꜛԜᴠᴠͼ꞉ꜜᴑᴒᴥ
Ⱪ͟
Ⱪꞌꜝꜝᴑͼꜞᴟᴒᴠᴠᴢᴟᴒ
Ⱪᴂ꜠
ⱩꞌꜝꜝᴑͼᴢᴟᴒԜͼꜜ꞉ᴡᴟꜝⱲᴒꜜ
ⱪ᷈᷄ⱷ꜠ⱶ
ⱪ᷈ͼ꞉ꜜⱳ꞉ԝ꞉ᴡꜝᴟ
ⱪⱴϸ
ⱪꜝᴑᴒͼꜝⱱͼⱴᴒᴑᴒᴟԜꞌͼϸᴒⱲᴢꞌԜᴡ꞉ꜝꜜᴠ
ⱪⱶ꜡
ⱪⱳ꞉ꜜᴒᴠᴒͼⱳԜꜛᴠᴡᴒᴟͼꜝᴣԜᴟᴦ
ⱪꜙ᷆ⱴ
ԜꜞꜞԜᴟᴒꜜᴡͼᴡꜝᴡԜꞌͼꜞꞌԜᴠꜛԜͼᴐꞌᴒԜᴟԜꜜᴐᴒͼԜⱱᴡᴒᴟͼᴒᴥᴡᴟԜᴣԜᴠᴐᴢꞌԜᴟͼԜᴑꜛ꞉ꜜ꞉ᴠᴡᴟԜᴡ꞉ꜝꜜ
ⱪꜛԜᴥ
ꜚԜᴥ꞉ꜛᴢꜛͼꜞꞌԜᴠꜛԜͼᴑᴟᴢⱲͼᴐꜝꜜᴐᴒꜜᴡᴟԜᴡ꞉ꜝꜜ
ⱪ꜡᷉
ⱪԜᴟԝꜝꜜͼᴑ꞉ꜝᴥ꞉ᴑᴒ
ⱪ͟ꜘ
ⱪᴟᴒԜᴡ꞉ꜜᴒͼꜞⱳꜝᴠꜞⱳꜝꞋ꞉ꜜԜᴠᴒ
ⱪϸⱴ
ⱪԜᴠᴒͼᴟᴒꜞꜝᴟᴡͼⱱꜝᴟꜛ
ⱪϸ꜡
ⱪꞌ꞉ꜜ꞉ᴐԜꞌͼϸᴒᴠᴒԜᴟᴐⱳͼ꜡ᴟⱲԜꜜ꞉ᴧԜᴡ꞉ꜝꜜ
ⱪᴀϸ
ⱪꞌ꞉ꜜ꞉ᴐԜꞌͼᴀᴡᴢᴑᴦͼϸᴒꜞꜝᴟᴡ

Ⱬᴅ᷄᷉Ⱡ᷊᷇
ⱪꞌ꞉ꜜ꞉ᴐԜꞌͼᴁᴟ꞉Ԝꞌͼ͟ᴟꜝᴡꜝᴐꜝꞌⱡͼⱫᴅ᷄᷉Ⱡ᷊᷊᷇᷄᷇
ⱨꜛᴒꜜᴑꜛᴒꜜᴡͼ᷊᷅᷇ͼⱴ꞉ꜜԜꞌⱡͼ᷇ⱠͼꜗԜꜜᴢԜᴟᴦ᷉᷇᷈ⅎ
ⱪꜝꜜⱱ꞉ᴑᴒꜜᴡ꞉Ԝꞌ
͟ԜⱲᴒͼ᷉Ⱡ
ⱫᴦԜᴥͼⱪꜝᴟꜞ᷅
Ⱬꜙᴁ
Ⱬꜝᴠᴒͼꜙ꞉ꜛ꞉ᴡ꞉ꜜⱲͼᴁꜝᴥ꞉ᴐ꞉ᴡᴦ
ⱫꜚⱷⱫ
Ⱬ꞉ᴣ꞉ᴠ꞉ꜝꜜͼꜝⱱͼꜚ꞉ᴐᴟꜝԝ꞉ꜝꞌꜝⱲᴦͼԜꜜᴑͼⱷꜜⱱᴒᴐᴡ꞉ꜝᴢᴠͼⱫ꞉ᴠᴒԜᴠᴒᴠ
Ⱬ͟
ⱫᴟᴢⱲͼꜞᴟꜝᴑᴢᴐᴡ
ⱫᴀꜚⱩ
ⱫԜᴡԜͼᴀԜⱱᴒᴡᴦͼꜚꜝꜜ꞉ᴡꜝᴟ꞉ꜜⱲⱩꜝԜᴟᴑ
ⱬⱪⱵ
ⱬꞌᴒᴐᴡᴟꜝᴐԜᴟᴑ꞉ꜝⱲᴟԜꜛ
ᴒⱪϸⱴ
ⱬꞌᴒᴐᴡᴟꜝꜜ꞉ᴐͼᴐԜᴠᴒͼᴟᴒꜞꜝᴟᴡͼⱱꜝᴟꜛ
ⱬⱫⱪ
ⱬꞌᴒᴐᴡᴟꜝꜜ꞉ᴐͼᴑԜᴡԜͼᴐԜꜞᴡᴢᴟᴒ
ⱬᴁ
ⱬԜᴟꞌᴦͼᴡᴒᴟꜛ꞉ꜜԜᴡ꞉ꜝꜜ
ⱬϷ᷿Ⱬ
ⱬᴢᴟꜝϷꜝꜙͼⱵᴟꜝᴢꜞͼ᷿᷄Ⱬ꞉ꜛᴒꜜᴠ꞉ꜝꜜͼϸᴒꜞꜝᴟᴡͼϷᴢᴒᴠᴡ꞉ꜝꜜꜜԜ꞉ᴟᴒ
ⱴᴄⱬϸ
ⱱԜꜛ꞉ꞌᴦ᷄ᴤ꞉ᴠᴒͼᴡᴦꜞᴒⱷᴒᴟᴟꜝᴟͼᴟԜᴡᴒ
ⱴⱫⱨ
ⱴꜝꜝᴑͼԜꜜᴑͼⱫᴟᴢⱲͼⱨᴑꜛ꞉ꜜ꞉ᴠᴡᴟԜᴡ꞉ꜝꜜ
ⱴᴅⱷӿԜԐ
ⱴԜᴐᴡꜝᴟͼᴅⱷͼӿԜᴐᴡ꞉ᴣԜᴡᴒᴑԐ
ⱴᴅⱷⱷӿԜԐ
ⱴԜᴐᴡꜝᴟͼᴅⱷⱷͼӿԜᴐᴡ꞉ᴣԜᴡᴒᴑԐ
Ⱶⱪ͟
Ⱶꜝꜝᴑͼⱪꞌ꞉ꜜ꞉ᴐԜꞌͼ͟ᴟԜᴐᴡ꞉ᴐᴒ
Ⱶⱬⱬ
ⱵᴒꜜᴒᴟԜꞌ꞉ᴧᴒᴑͼᴒᴠᴡ꞉ꜛԜᴡ꞉ꜜⱲͼᴒꜟᴢԜᴡ꞉ꜝꜜ
ⱵⱵᴁ
ⱵԜꜛꜛԜ᷄ⱲꞌᴢᴡԜꜛᴦꞌͼᴡᴟԜꜜᴠⱱᴒᴟԜᴠᴒ
ⱶⱨⱬ
ⱶᴒᴟᴒᴑ꞉ᴡԜᴟᴦͼԜꜜⱲ꞉ꜝᴒᴑᴒꜛԜ
ⱶⱩᴠⱨⱲ
ⱶᴒꜞԜᴡ꞉ᴡ꞉ᴠͼⱩͼᴠᴢᴟⱱԜᴐᴒͼԜꜜᴡ꞉Ⱳᴒꜜ
ⱶⱪᴃ
ⱶᴒꜞԜᴡ꞉ᴡ꞉ᴠͼⱪͼᴣ꞉ᴟᴢᴠ
ⱶⱷ͟ⱨⱨ
ⱶᴒԜꞌᴡⱳͼⱷꜜⱱꜝᴟꜛԜᴡ꞉ꜝꜜͼ͟ꜝᴟᴡԜԝ꞉ꞌ꞉ᴡᴦͼԜꜜᴑͼⱨᴐᴐꜝᴢꜜᴡԜԝ꞉ꞌ꞉ᴡᴦͼⱨᴐᴡ
ⱶⱷᴃ
ⱶᴢꜛԜꜜͼ꞉ꜛꜛᴢꜜꜝᴑᴒⱱ꞉ᴐ꞉ᴒꜜᴐᴦͼᴣ꞉ᴟᴢᴠ
ⱶꜚᴄꜘ
ⱶ꞉ⱲⱳͼꜛꜝꞌᴒᴐᴢꞌԜᴟͼᴤᴒ꞉ⱲⱳᴡͼꞋ꞉ꜜ꞉ꜜꜝⱲᴒꜜ
ⱶϸ
ⱶᴒԜᴟᴡͼᴟԜᴡᴒ
ⱷⱪⱶ
ⱷꜜᴡᴒᴟꜜԜᴡ꞉ꜝꜜԜꞌͼⱪꜝꜜⱱᴒᴟᴒꜜᴐᴒͼꜝꜜͼⱶԜᴟꜛꜝꜜ꞉ᴠԜᴡ꞉ꜝꜜͼꜝⱱͼᴁᴒᴐⱳꜜ꞉ᴐԜꞌͼϸᴒꜟᴢ꞉ᴟᴒꜛᴒꜜᴡᴠͼ
ⱱꜝᴟͼϸᴒⱲ꞉ᴠᴡᴟԜᴡ꞉ꜝꜜͼꜝⱱͼ͟ⱳԜᴟꜛԜᴐᴒᴢᴡ꞉ᴐԜꞌᴠͼⱱꜝᴟͼⱶᴢꜛԜꜜͼᴂᴠᴒ
ⱷⱬⱪ
ⱷꜜᴑᴒꜞᴒꜜᴑᴒꜜᴡͼⱬᴡⱳ꞉ᴐᴠͼⱪꜝꜛꜛ꞉ᴡᴡᴒᴒ
ⱷⱲⱵ
ⱷꜛꜛᴢꜜꜝⱲꞌꜝԝᴢꞌ꞉ꜜͼⱵ
ⱷⱲⱵ᷈
ⱷꜛꜛᴢꜜꜝⱲꞌꜝԝᴢꞌ꞉ꜜͼⱵͼᴠᴢԝᴐꞌԜᴠᴠͼ᷈
ⱷꜚ͟
ⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡ꞉ꜝꜜԜꞌͼꜛᴒᴑ꞉ᴐ꞉ꜜԜꞌͼꜞᴟꜝᴑᴢᴐᴡ
ⱷ꜠Ⱬ
ⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡ꞉ꜝꜜԜꞌͼ꜠ᴒᴤͼⱫᴟᴢⱲ

Ⱬᴅ᷄᷉Ⱡ᷊᷇
ⱪꞌ꞉ꜜ꞉ᴐԜꞌͼᴁᴟ꞉Ԝꞌͼ͟ᴟꜝᴡꜝᴐꜝꞌⱡͼⱫᴅ᷄᷉Ⱡ᷊᷊᷇᷄᷇
ⱨꜛᴒꜜᴑꜛᴒꜜᴡͼ᷊᷅᷇ͼⱴ꞉ꜜԜꞌⱡͼ᷇ⱠͼꜗԜꜜᴢԜᴟᴦ᷉᷇᷈ⅎ
ⱪꜝꜜⱱ꞉ᴑᴒꜜᴡ꞉Ԝꞌ
͟ԜⱲᴒͼ᷊᷇
ⱫᴦԜᴥͼⱪꜝᴟꜞ᷅
ⱷ꜠ϸ
ⱷꜜᴡᴒᴟꜜԜᴡ꞉ꜝꜜԜꞌͼꜜꜝᴟꜛԜꞌ꞉ᴧᴒᴑͼᴟԜᴡ꞉ꜝ
ⱷϸⱩ
ⱷꜜᴠᴡ꞉ᴡᴢᴡ꞉ꜝꜜԜꞌͼϸᴒᴣ꞉ᴒᴤͼⱩꜝԜᴟᴑ
ⱷᴂⱫ
ⱷꜜᴡᴟԜᴢᴡᴒᴟ꞉ꜜᴒͼᴑᴒᴣ꞉ᴐᴒ
ⱷᴂᴀ
ⱷꜜᴡᴟԜᴢᴡᴒᴟ꞉ꜜᴒͼⱳꜝᴟꜛꜝꜜᴒͼᴟᴒꞌᴒԜᴠ꞉ꜜⱲͼᴠᴦᴠᴡᴒꜛᴠ
ⱷᴃ
ⱷꜜᴡᴟԜᴣᴒꜜꜝᴢᴠ
ⱷᴄϸᴀ
ⱷꜜᴡᴒᴟԜᴐᴡ꞉ᴣᴒͼᴄᴒԝ᷄ԝԜᴠᴒᴑͼϸԜꜜᴑꜝꜛ꞉ᴧԜᴡ꞉ꜝꜜͼᴀᴦᴠᴡᴒꜛ
ꜘ꞉
꞉ꜜⱳ꞉ԝ꞉ᴡ꞉ꜝꜜͼᴐꜝꜜᴠᴡԜꜜᴡ
ꜙⱫⱶ
ꜙԜᴐᴡԜᴡᴒͼᴑᴒⱳᴦᴑᴟꜝⱲᴒꜜԜᴠᴒ
ꜙ꜡ⱪⱴ
ꜙԜᴠᴡͼꜝԝᴠᴒᴟᴣԜᴡ꞉ꜝꜜͼᴐԜᴟᴟ꞉ᴒᴑͼⱱꜝᴟᴤԜᴟᴑ
ꜙᴁ͟
ꜙꜝꜜⱲ᷄ᴁᴒᴟꜛͼ͟ᴟꜝꜞⱳᴦꞌԜᴐᴡ꞉ᴐ
ꜚⱪⱶ
ꜚᴒԜꜜͼᴐꜝᴟꜞᴢᴠᴐᴢꞌԜᴟͼⱳᴒꜛꜝⱲꞌꜝԝ꞉ꜜ
ꜚⱪⱶⱪ
ꜚᴒԜꜜͼᴐꜝᴟꜞᴢᴠᴐᴢꞌԜᴟͼⱳᴒꜛꜝⱲꞌꜝԝ꞉ꜜͼᴐꜝꜜᴐᴒꜜᴡᴟԜᴡ꞉ꜝꜜ
ꜚⱪᴃ
ꜚᴒԜꜜͼᴐꜝᴟꜞᴢᴠᴐᴢꞌԜᴟͼᴣꜝꞌᴢꜛᴒ
ꜚᴒᴑⱫϸⱨ
ꜚᴒᴑ꞉ᴐԜꞌͼⱫ꞉ᴐᴡ꞉ꜝꜜԜᴟᴦͼⱱꜝᴟͼϸᴒⱲᴢꞌԜᴡꜝᴟᴦͼⱨᴐᴡ꞉ᴣ꞉ᴡ꞉ᴒᴠ
ꜚꜚϸꜚ
ꜚ꞉ᴥᴒᴑͼꜛꜝᴑᴒꞌͼᴟᴒꜞᴒԜᴡᴒᴑͼꜛᴒԜᴠᴢᴟᴒᴠ
꜡ꜙⱬ
꜡ꜞᴒꜜ᷄ꞌԜԝᴒꞌͼᴒᴥᴡᴒꜜᴠ꞉ꜝꜜ
͟Ⱬ
͟ⱳԜᴟꜛԜᴐꜝᴑᴦꜜԜꜛ꞉ᴐӿᴠԐ
͟ꜘ
͟ⱳԜᴟꜛԜᴐꜝꞋ꞉ꜜᴒᴡ꞉ᴐӿᴠԐ
ꜞꜘԜꞌ
͟ꞌԜᴠꜛԜͼꞋԜꞌꞌ꞉Ꞌᴟᴒ꞉ꜜ
͟ᴁ
͟ᴟꜝᴡⱳᴟꜝꜛԝ꞉ꜜͼᴡ꞉ꜛᴒ
Ϸꜝꜙ
ϷᴢԜꞌ꞉ᴡᴦͼꜝⱱͼꜙ꞉ⱱᴒ
ϸⱬⱩ
ϸᴒᴠᴒԜᴟᴐⱳͼⱬᴡⱳ꞉ᴐᴠͼⱩꜝԜᴟᴑ
ϸⱩⱪ
ϸᴒᴑͼԝꞌꜝꜝᴑͼᴐᴒꞌꞌͼӿᴐꜝᴢꜜᴡԐ
ϸϸ
ϸᴒᴠꜞ꞉ᴟԜᴡꜝᴟᴦͼᴟԜᴡᴒ
ᴀⱨⱬ
ᴀᴒᴟ꞉ꜝᴢᴠͼԜᴑᴣᴒᴟᴠᴒͼᴒᴣᴒꜜᴡ
ᴀⱨ͟
ᴀᴡԜᴡ꞉ᴠᴡ꞉ᴐԜꞌͼⱨꜜԜꞌᴦᴠ꞉ᴠͼ͟ꞌԜꜜ
ᴀⱪ
ᴀᴢԝᴐᴢᴡԜꜜᴒꜝᴢᴠ
ᴀⱫ
ᴀᴡԜꜜᴑԜᴟᴑͼᴑᴒᴣ꞉Ԝᴡ꞉ꜝꜜ
ᴀⱵ꜡ᴁ
ᴀᴒᴟᴢꜛͼⱲꞌᴢᴡԜꜛ꞉ᴐͼꜝᴥԜꞌꜝԜᴐᴒᴡ꞉ᴐͼᴡᴟԜꜜᴠԜꜛ꞉ꜜԜᴠᴒͼӿⱨᴀᴁԐ

Ⱬᴅ᷄᷉Ⱡ᷊᷇
ⱪꞌ꞉ꜜ꞉ᴐԜꞌͼᴁᴟ꞉Ԝꞌͼ͟ᴟꜝᴡꜝᴐꜝꞌⱡͼⱫᴅ᷄᷉Ⱡ᷊᷊᷇᷄᷇
ⱨꜛᴒꜜᴑꜛᴒꜜᴡͼ᷊᷅᷇ͼⱴ꞉ꜜԜꞌⱡͼ᷇ⱠͼꜗԜꜜᴢԜᴟᴦ᷉᷇᷈ⅎ
ⱪꜝꜜⱱ꞉ᴑᴒꜜᴡ꞉Ԝꞌ
͟ԜⱲᴒͼ᷊᷈
ⱫᴦԜᴥͼⱪꜝᴟꜞ᷅
ᴀⱵ͟ᴁ
ᴀᴒᴟᴢꜛͼⱲꞌᴢᴡԜꜛ꞉ᴐͼꜞᴦᴟᴢᴣ꞉ᴐͼᴡᴟԜꜜᴠԜꜛ꞉ꜜԜᴠᴒͼӿⱨꜙᴁԐ
ᴀꜚ
ᴀԜⱱᴒᴡᴦͼꜚԜꜜԜⱲᴒꜛᴒꜜᴡ
ᴀꜚϷ
ᴀᴡԜꜜᴑԜᴟᴑͼꜚᴒᴑⱫϸⱨͼꜟᴢᴒᴟᴦ
ᴀ꜡ⱪ
ᴀᴦᴠᴡᴒꜛͼ꜡ᴟⱲԜꜜͼⱪꞌԜᴠᴠ
ᴀ꜡͟
ᴀᴡԜꜜᴑԜᴟᴑͼꜝꜞᴒᴟԜᴡ꞉ꜜⱲͼꜞᴟꜝᴐᴒᴑᴢᴟᴒ
ᴡӷ
ᴁᴒᴟꜛ꞉ꜜԜꞌͼᴒꞌ꞉ꜛ꞉ꜜԜᴡ꞉ꜝꜜͼⱳԜꞌⱱ᷄ꞌ꞉ⱱᴒ
ᴡꜛԜᴥ
ᴁ꞉ꜛᴒͼᴡꜝͼꜛԜᴥ꞉ꜛᴢꜛͼꜞꞌԜᴠꜛԜͼᴐꜝꜜᴐᴒꜜᴡᴟԜᴡ꞉ꜝꜜ
ᴁⱬⱨⱬ
ᴁᴟᴒԜᴡꜛᴒꜜᴡ᷄ⱬꜛᴒᴟⱲᴒꜜᴡͼⱨᴑᴣᴒᴟᴠᴒͼⱬᴣᴒꜜᴡ
ᴁᴁ
ᴁⱳᴟꜝꜛԝ꞉ꜜͼᴡ꞉ꜛᴒ
ᴂᴀ
ᴂꜜ꞉ᴡᴒᴑͼᴀᴡԜᴡᴒᴠ
ᴃᴑ᷆ⱴ
ⱨꜞꜞԜᴟᴒꜜᴡͼᴣꜝꞌᴢꜛᴒͼꜝⱱͼᴑ꞉ᴠᴡᴟ꞉ԝᴢᴡ꞉ꜝꜜᴑᴢᴟ꞉ꜜⱲͼᴡᴒᴟꜛ꞉ꜜԜꞌͼꜞⱳԜᴠᴒͼԜⱱᴡᴒᴟͼᴒᴥᴡᴟԜᴣԜᴠᴐᴢꞌԜᴟͼ
Ԝᴑꜛ꞉ꜜ꞉ᴠᴡᴟԜᴡ꞉ꜝꜜ
ᴄⱩⱪ
ᴄⱳ꞉ᴡᴒͼԝꞌꜝꜝᴑͼᴐᴒꞌꞌͼӿᴐꜝᴢꜜᴡԐ
ᴄⱶ꜡
ᴄꜝᴟꞌᴑͼⱶᴒԜꞌᴡⱳͼ꜡ᴟⱲԜꜜ꞉ᴧԜᴡ꞉ꜝꜜ

Ⱬᴅ᷄᷉Ⱡ᷊᷇
ⱪꞌ꞉ꜜ꞉ᴐԜꞌͼᴁᴟ꞉Ԝꞌͼ͟ᴟꜝᴡꜝᴐꜝꞌⱡͼⱫᴅ᷄᷉Ⱡ᷊᷊᷇᷄᷇
ⱨꜛᴒꜜᴑꜛᴒꜜᴡͼ᷊᷅᷇ͼⱴ꞉ꜜԜꞌⱡͼ᷇ⱠͼꜗԜꜜᴢԜᴟᴦ᷉᷇᷈ⅎ
ⱪꜝꜜⱱ꞉ᴑᴒꜜᴡ꞉Ԝꞌ
͟ԜⱲᴒͼ᷊᷉
ⱫᴦԜᴥͼⱪꜝᴟꜞ᷅
1
INTRODUCTION
1.1
DX-2930
Ⱬᴅ᷄᷉Ⱡ᷊᷇ͼ꞉ᴠͼԜͼⱱᴢꞌꞌᴦͼⱳᴢꜛԜꜜͼⱷⱲⱵ᷈ͼᴟᴒᴐꜝꜛԝ꞉ꜜԜꜜᴡͼꜛꜝꜜꜝᴐꞌꜝꜜԜꞌͼԜꜜᴡ꞉ԝꜝᴑᴦͼᴡⱳԜᴡͼԝ꞉ꜜᴑᴠͼᴠꜞᴒᴐ꞉ⱱ꞉ᴐԜꞌꞌᴦͼᴡꜝͼ
Ԝᴐᴡ꞉ᴣᴒͼꜞꞌԜᴠꜛԜͼꞋԜꞌꞌ꞉Ꞌᴟᴒ꞉ꜜ᷅ͼⱫᴅ᷄᷉Ⱡ᷊᷇ͼ꞉ᴠͼԝᴒ꞉ꜜⱲͼᴑᴒᴣᴒꞌꜝꜞᴒᴑͼⱱꜝᴟͼꜞᴟꜝꜞⱳᴦꞌԜᴐᴡ꞉ᴐͼᴡᴟᴒԜᴡꜛᴒꜜᴡͼꜝⱱͼԜꜜⱲ꞉ꜝᴒᴑᴒꜛԜͼ
ԜᴡᴡԜᴐꞋᴠͼ꞉ꜜͼꜞԜᴡ꞉ᴒꜜᴡᴠͼᴤ꞉ᴡⱳͼⱳᴒᴟᴒᴑ꞉ᴡԜᴟᴦͼԜꜜⱲ꞉ꜝᴒᴑᴒꜛԜͼӿⱶⱨⱬԐԓͼԜͼᴠᴒᴟ꞉ꜝᴢᴠͼԜꜜᴑͼꞌ꞉ⱱᴒ᷄ᴡⱳᴟᴒԜᴡᴒꜜ꞉ꜜⱲͼᴑ꞉ᴠᴒԜᴠᴒ᷅
1.2
Hereditary Angioedema
ⱶⱨⱬͼ꞉ᴠͼԜͼꞌꜝꜜⱲ᷄ᴡᴒᴟꜛԓͼᴑᴒԝ꞉ꞌ꞉ᴡԜᴡ꞉ꜜⱲԓͼԜꜜᴑͼꞌ꞉ⱱᴒ᷄ᴡⱳᴟᴒԜᴡᴒꜜ꞉ꜜⱲͼᴑ꞉ᴠᴒԜᴠᴒͼᴐԜᴢᴠᴒᴑͼԝᴦͼꜛᴢᴡԜᴡ꞉ꜝꜜᴠͼ꞉ꜜͼᴡⱳᴒͼ
ⱪ᷈᷄꞉ꜜⱳ꞉ԝ꞉ᴡꜝᴟͼӿⱪ᷈᷄ⱷ꜠ⱶԐͼⱲᴒꜜᴒԓͼᴟᴒᴠᴢꞌᴡ꞉ꜜⱲͼ꞉ꜜͼᴑᴒⱱ꞉ᴐ꞉ᴒꜜᴐᴦͼꜝᴟͼᴑᴦᴠⱱᴢꜜᴐᴡ꞉ꜝꜜͼꜝⱱͼⱪ᷈᷄ⱷ꜠ⱶͼꜞᴟꜝᴡᴒ꞉ꜜ᷅ͼⱶⱨⱬͼ
ꜛԜꜜ꞉ⱱᴒᴠᴡᴠͼᴐꞌ꞉ꜜ꞉ᴐԜꞌꞌᴦͼԜᴠͼᴢꜜꜞᴟᴒᴑ꞉ᴐᴡԜԝꞌᴒԓͼ꞉ꜜᴡᴒᴟꜛ꞉ᴡᴡᴒꜜᴡͼԜᴡᴡԜᴐꞋᴠͼꜝⱱͼᴠᴢԝᴐᴢᴡԜꜜᴒꜝᴢᴠͼꜝᴟͼᴠᴢԝꜛᴢᴐꜝᴠԜꞌͼᴒᴑᴒꜛԜͼ
ꜝⱱͼᴡⱳᴒͼⱱԜᴐᴒԓͼꞌԜᴟᴦꜜᴥԓͼⱲԜᴠᴡᴟꜝ꞉ꜜᴡᴒᴠᴡ꞉ꜜԜꞌͼᴡᴟԜᴐᴡԓͼꞌ꞉ꜛԝᴠͼԜꜜᴑ᷆ꜝᴟͼⱲᴒꜜ꞉ᴡԜꞌ꞉ԜͼӿᴇᴢᴟԜᴤԓͼ᷉᷇᷇˲Ԑ᷅ͼᴀᴤᴒꞌꞌ꞉ꜜⱲͼꜛԜᴦͼꞌԜᴠᴡͼ
ᴢꜞͼᴡꜝͼⱱ꞉ᴣᴒͼꜝᴟͼꜛꜝᴟᴒͼᴑԜᴦᴠⱢͼꜛꜝᴠᴡͼꜞԜᴡ꞉ᴒꜜᴡᴠͼᴠᴢⱱⱱᴒᴟͼꜛᴢꞌᴡ꞉ꜞꞌᴒͼԜᴡᴡԜᴐꞋᴠͼꜞᴒᴟͼᴦᴒԜᴟ᷅ͼⱶⱨⱬͼ꞉ᴠͼԜꜜͼꜝᴟꜞⱳԜꜜͼ
ᴑ꞉ᴠꜝᴟᴑᴒᴟ᷅ͼᴁⱳᴒͼᴒᴥԜᴐᴡͼꜞᴟᴒᴣԜꞌᴒꜜᴐᴒͼꜝⱱͼⱶⱨⱬͼ꞉ᴠͼᴢꜜꞋꜜꜝᴤꜜԓͼԝᴢᴡͼᴐᴢᴟᴟᴒꜜᴡͼᴒᴠᴡ꞉ꜛԜᴡᴒᴠͼᴟԜꜜⱲᴒͼⱱᴟꜝꜛͼ᷈ͼꜞᴒᴟͼ
᷈᷇ԓ᷇᷇᷇ͼᴡꜝͼ᷈ͼꜞᴒᴟͼ᷿᷈᷇ԓ᷇᷇᷇ͼꜞᴒᴟᴠꜝꜜᴠԓͼᴤ꞉ᴡⱳͼꜛԜꜜᴦͼԜᴢᴡⱳꜝᴟᴠͼԜⱲᴟᴒᴒ꞉ꜜⱲͼᴡⱳԜᴡͼ᷈ꜞᴒᴟ᷿᷇ԓ᷇᷇᷇ͼ꞉ᴠͼꞌ꞉Ꞌᴒꞌᴦͼᴡⱳᴒͼ
ᴐꞌꜝᴠᴒᴠᴡͼᴒᴠᴡ꞉ꜛԜᴡᴒͼӿⱩᴦⱲᴢꜛԓͼ᷉᷇᷇ⱠⱢͼⱵꜝᴟ꞉ꜜⱲͼᴒᴡͼԜꞌ᷅ԓͼ᷈ⱠⱠ˲Ɫͼꜙᴒ꞉ͼᴒᴡͼԜꞌ᷅ԓͼ᷉᷇᷈᷈Ɫͼ꜠ꜝᴟᴑᴒꜜⱱᴒꞌᴡͼᴒᴡͼԜꞌ᷅ԓͼ᷉᷇᷈᷾Ɫͼ
ϸꜝᴐⱳᴒͼᴒᴡͼԜꞌ᷅ԓͼ᷿᷉᷇᷇Ԑ᷅ͼ
ᴀᴤᴒꞌꞌ꞉ꜜⱲͼ꞉ꜜͼᴡⱳᴒͼꞌԜᴟᴦꜜᴥͼᴐԜꜜͼꜝԝᴠᴡᴟᴢᴐᴡͼᴡⱳᴒͼԜ꞉ᴟᴤԜᴦᴠͼԜꜜᴑͼᴐԜᴢᴠᴒͼᴑᴒԜᴡⱳͼⱱᴟꜝꜛͼԜᴠꜞⱳᴦᴥ꞉Ԝᴡ꞉ꜝꜜͼӿⱩꜝᴟꞋͼᴒᴡͼԜꞌ᷅ԓͼ
᷉᷇᷈᷉ⱢͼⱩꜝᴟꞋͼᴒᴡͼԜꞌ᷅ԓͼ᷉᷇᷇᷇Ԑ᷅ͼⱨꜞꜞᴟꜝᴥ꞉ꜛԜᴡᴒꞌᴦͼ᷿᷇ӼͼꜝⱱͼԜꞌꞌͼⱶⱨⱬͼꜞԜᴡ꞉ᴒꜜᴡᴠͼᴤ꞉ꞌꞌͼᴒᴥꜞᴒᴟ꞉ᴒꜜᴐᴒͼԜͼꞌԜᴟᴦꜜⱲᴒԜꞌͼ
ԜᴡᴡԜᴐꞋͼ꞉ꜜͼᴡⱳᴒ꞉ᴟͼꞌ꞉ⱱᴒᴡ꞉ꜛᴒԓͼԜꜜᴑͼᴡⱳᴒᴟᴒͼ꞉ᴠͼꜜꜝͼᴤԜᴦͼᴡꜝͼꜞᴟᴒᴑ꞉ᴐᴡͼᴤⱳ꞉ᴐⱳͼꜞԜᴡ꞉ᴒꜜᴡᴠͼԜᴟᴒͼԜᴡͼᴟ꞉ᴠꞋͼꜝⱱͼԜͼꞌԜᴟᴦꜜⱲᴒԜꞌͼ
ԜᴡᴡԜᴐꞋͼӿⱩꜝᴟꞋͼᴒᴡͼԜꞌ᷅ԓͼ᷊᷉᷇᷇ⱢͼⱩꜝᴟꞋͼᴒᴡͼԜꞌ᷅ԓͼ᷉᷇᷇⅍Ԑ᷅ͼ
ⱨԝᴑꜝꜛ꞉ꜜԜꞌͼԜᴡᴡԜᴐꞋᴠͼԜᴟᴒͼꜝⱱᴡᴒꜜͼԜᴠᴠꜝᴐ꞉Ԝᴡᴒᴑͼᴤ꞉ᴡⱳͼꜜԜᴢᴠᴒԜԓͼᴣꜝꜛ꞉ᴡ꞉ꜜⱲԓͼԜꜜᴑͼᴠᴒᴣᴒᴟᴒͼꜞԜ꞉ꜜⱢͼ꞉ꜜᴡᴒᴠᴡ꞉ꜜԜꞌͼ
ᴠᴦꜛꜞᴡꜝꜛᴠͼᴟᴒᴠᴒꜛԝꞌ꞉ꜜⱲͼԜԝᴑꜝꜛ꞉ꜜԜꞌͼᴒꜛᴒᴟⱲᴒꜜᴐ꞉ᴒᴠͼꜛԜᴦͼꞌᴒԜᴑͼᴡꜝͼᴢꜜꜜᴒᴐᴒᴠᴠԜᴟᴦͼᴠᴢᴟⱲᴒᴟᴦͼӿᴇᴢᴟԜᴤԓͼ᷉᷇᷇˲Ԑ᷅ͼ
ⱨꜞꜞᴟꜝᴥ꞉ꜛԜᴡᴒꞌᴦͼ˲᷿ӼͼꜝⱱͼꜞԜᴡ꞉ᴒꜜᴡᴠͼⱳԜᴣᴒͼᴁᴦꜞᴒͼⱷͼⱶⱨⱬԓͼᴐⱳԜᴟԜᴐᴡᴒᴟ꞉ᴧᴒᴑͼԝᴦͼᴣᴒᴟᴦͼꞌꜝᴤͼꜞᴟꜝᴑᴢᴐᴡ꞉ꜝꜜͼꜝⱱͼ
ⱱᴢꜜᴐᴡ꞉ꜝꜜԜꞌꞌᴦͼꜜꜝᴟꜛԜꞌͼⱪ᷈᷄ⱷ꜠ⱶͼꜞᴟꜝᴡᴒ꞉ꜜԓͼᴤⱳ꞉ꞌᴒͼᴡⱳᴒͼᴟᴒꜛԜ꞉ꜜ꞉ꜜⱲͼԜꜞꜞᴟꜝᴥ꞉ꜛԜᴡᴒꞌᴦͼ᷿᷈ӼͼꜝⱱͼꜞԜᴡ꞉ᴒꜜᴡᴠͼⱳԜᴣᴒͼ
ᴁᴦꜞᴒͼⱷⱷͼⱶⱨⱬͼԜꜜᴑͼꜞᴟꜝᴑᴢᴐᴒͼꜜꜝᴟꜛԜꞌͼꜝᴟͼᴒꞌᴒᴣԜᴡᴒᴑͼꞌᴒᴣᴒꞌᴠͼꜝⱱͼԜͼⱱᴢꜜᴐᴡ꞉ꜝꜜԜꞌꞌᴦͼ꞉ꜛꜞԜ꞉ᴟᴒᴑͼⱪ᷈᷄ⱷ꜠ⱶͼӿᴇᴢᴟԜᴤԓͼ
᷉᷇᷇˲Ԑ᷅ͼⱷꜜͼꜞԜᴡ꞉ᴒꜜᴡᴠͼᴤ꞉ᴡⱳͼᴁᴦꜞᴒᴠͼⱷͼԜꜜᴑͼⱷⱷͼⱶⱨⱬԓͼᴢꜜᴐꜝꜜᴡᴟꜝꞌꞌᴒᴑͼꜞꞌԜᴠꜛԜͼꞋԜꞌꞌ꞉Ꞌᴟᴒ꞉ꜜͼⱲᴒꜜᴒᴟԜᴡ꞉ꜝꜜͼᴟᴒᴠᴢꞌᴡᴠͼ꞉ꜜͼ
ᴒᴥᴐᴒᴠᴠͼԝᴟԜᴑᴦꞋ꞉ꜜ꞉ꜜͼᴟᴒꞌᴒԜᴠᴒͼⱱᴟꜝꜛͼⱳ꞉Ⱳⱳ᷄ꜛꜝꞌᴒᴐᴢꞌԜᴟͼᴤᴒ꞉ⱲⱳᴡͼꞋ꞉ꜜ꞉ꜜꜝⱲᴒꜜͼӿⱶꜚᴄꜘԐͼԜꜜᴑͼᴣԜᴠᴐᴢꞌԜᴟͼꞌᴒԜꞋͼ
ꜛᴒᴑ꞉ԜᴡᴒᴑͼԝᴦͼԝᴟԜᴑᴦꞋ꞉ꜜ꞉ꜜͼԝ꞉ꜜᴑ꞉ꜜⱲͼᴡꜝͼᴡⱳᴒͼⱩ᷉ͼᴟᴒᴐᴒꜞᴡꜝᴟͼӿⱩ᷉᷄ϸԐͼꜝꜜͼᴡⱳᴒͼᴠᴢᴟⱱԜᴐᴒͼꜝⱱͼᴒꜜᴑꜝᴡⱳᴒꞌ꞉Ԝꞌͼᴐᴒꞌꞌᴠͼ
ӿᴇᴢᴟԜᴤԓͼ᷉᷇᷇˲Ԑ᷅ͼⱪꞌ꞉ꜜ꞉ᴐԜꞌͼᴠᴢᴠꜞ꞉ᴐ꞉ꜝꜜͼꜝⱱͼᴁᴦꜞᴒᴠͼⱷͼԜꜜᴑͼⱷⱷͼⱶⱨⱬͼᴐԜꜜͼԝᴒͼᴐꜝꜜⱱ꞉ᴟꜛᴒᴑͼԝᴦͼԜᴣԜ꞉ꞌԜԝꞌᴒͼԝꞌꜝꜝᴑͼ
ᴡᴒᴠᴡᴠ᷅ͼⱷꜜͼԜᴑᴑ꞉ᴡ꞉ꜝꜜͼᴡꜝͼԜԝꜜꜝᴟꜛԜꞌ꞉ᴡ꞉ᴒᴠͼ꞉ꜜͼⱪ᷈᷄ⱷ꜠ⱶͼꞌᴒᴣᴒꞌͼԜꜜᴑͼⱱᴢꜜᴐᴡ꞉ꜝꜜԓͼꜞꞌԜᴠꜛԜͼⱪ᷾ͼꞌᴒᴣᴒꞌᴠͼԜᴟᴒͼꜛԜᴟꞋᴒᴑꞌᴦͼ
ᴟᴒᴑᴢᴐᴒᴑͼԜᴡͼԜꞌꞌͼᴡ꞉ꜛᴒᴠͼ꞉ꜜͼԝꞌꜝꜝᴑͼⱱᴟꜝꜛͼꜛꜝᴠᴡͼꜞԜᴡ꞉ᴒꜜᴡᴠ᷅
1.3
Therapeutic Rationale for DX-2930
͟ꞌԜᴠꜛԜͼꞋԜꞌꞌ꞉Ꞌᴟᴒ꞉ꜜͼꜞꞌԜᴦᴠͼԜͼᴐᴟ꞉ᴡ꞉ᴐԜꞌͼᴟꜝꞌᴒͼ꞉ꜜͼᴡⱳᴒͼꜞԜᴡⱳꜝⱲᴒꜜᴒᴠ꞉ᴠͼꜝⱱͼⱶⱨⱬͼԜᴡᴡԜᴐꞋᴠͼӿⱫԜᴣ꞉ᴠԓͼ᷉᷇᷇⅍ⱢͼꜘԜꜞꞌԜꜜͼ
Ԝꜜᴑͼꜗꜝᴠᴒꜞⱳԓͼ᷉᷇᷈᷇Ԑ᷅ͼⱷꜜͼꜜꜝᴟꜛԜꞌͼꜞⱳᴦᴠ꞉ꜝꞌꜝⱲᴦԓͼⱪ᷈᷄ⱷ꜠ⱶͼᴟᴒⱲᴢꞌԜᴡᴒᴠͼᴡⱳᴒͼԜᴐᴡ꞉ᴣ꞉ᴡᴦͼꜝⱱͼꜞꞌԜᴠꜛԜͼꞋԜꞌꞌ꞉Ꞌᴟᴒ꞉ꜜͼԜᴠͼ
ᴤᴒꞌꞌͼԜᴠͼԜͼᴣԜᴟ꞉ᴒᴡᴦͼꜝⱱͼꜝᴡⱳᴒᴟͼꜞᴟꜝᴡᴒԜᴠᴒᴠԓͼᴠᴢᴐⱳͼԜᴠͼⱪ᷈ᴟԓͼⱪ᷈ᴠԓͼⱱԜᴐᴡꜝᴟᴅⱷԜԓͼԜꜜᴑͼⱱԜᴐᴡꜝᴟͼᴅⱷⱷԜ᷅ͼ͟ꞌԜᴠꜛԜͼ
ꞋԜꞌꞌ꞉Ꞌᴟᴒ꞉ꜜͼᴟᴒⱲᴢꞌԜᴡᴒᴠͼᴡⱳᴒͼᴟᴒꞌᴒԜᴠᴒͼꜝⱱͼԝᴟԜᴑᴦꞋ꞉ꜜ꞉ꜜͼⱱᴟꜝꜛͼⱳ꞉ⱲⱳͼꜛꜝꞌᴒᴐᴢꞌԜᴟͼᴤᴒ꞉ⱲⱳᴡͼꞋ꞉ꜜ꞉ꜜꜝⱲᴒꜜͼӿⱶꜚᴄꜘԐ᷅ͼ
ⱫᴢᴒͼᴡꜝͼԜͼᴑᴒⱱ꞉ᴐ꞉ᴒꜜᴐᴦͼꜝⱱͼⱪ᷈᷄ⱷ꜠ⱶͼ꞉ꜜͼⱶⱨⱬԓͼᴢꜜᴐꜝꜜᴡᴟꜝꞌꞌᴒᴑͼꜞꞌԜᴠꜛԜͼꞋԜꞌꞌ꞉Ꞌᴟᴒ꞉ꜜͼԜᴐᴡ꞉ᴣ꞉ᴡᴦͼꜝᴐᴐᴢᴟᴠͼԜꜜᴑͼꞌᴒԜᴑᴠͼ
ᴡꜝͼᴡⱳᴒͼᴒᴥᴐᴒᴠᴠ꞉ᴣᴒͼⱲᴒꜜᴒᴟԜᴡ꞉ꜝꜜͼꜝⱱͼԝᴟԜᴑᴦꞋ꞉ꜜ꞉ꜜ᷅ͼⱩᴟԜᴑᴦꞋ꞉ꜜ꞉ꜜͼ꞉ᴠͼԜͼᴣԜᴠꜝᴑ꞉ꞌԜᴡꜝᴟͼᴤⱳ꞉ᴐⱳͼ꞉ᴠͼᴡⱳꜝᴢⱲⱳᴡͼᴡꜝͼԝᴒͼ

Ⱬᴅ᷄᷉Ⱡ᷊᷇
ⱪꞌ꞉ꜜ꞉ᴐԜꞌͼᴁᴟ꞉Ԝꞌͼ͟ᴟꜝᴡꜝᴐꜝꞌⱡͼⱫᴅ᷄᷉Ⱡ᷊᷊᷇᷄᷇
ⱨꜛᴒꜜᴑꜛᴒꜜᴡͼ᷊᷅᷇ͼⱴ꞉ꜜԜꞌⱡͼ᷇ⱠͼꜗԜꜜᴢԜᴟᴦ᷉᷇᷈ⅎ
ⱪꜝꜜⱱ꞉ᴑᴒꜜᴡ꞉Ԝꞌ
͟ԜⱲᴒͼ᷊᷊
ⱫᴦԜᴥͼⱪꜝᴟꜞ᷅
ᴟᴒᴠꜞꜝꜜᴠ꞉ԝꞌᴒͼⱱꜝᴟͼᴡⱳᴒͼᴐⱳԜᴟԜᴐᴡᴒᴟ꞉ᴠᴡ꞉ᴐͼⱶⱨⱬͼᴠᴦꜛꜞᴡꜝꜛᴠͼꜝⱱͼꞌꜝᴐԜꞌ꞉ᴧᴒᴑͼᴠᴤᴒꞌꞌ꞉ꜜⱲԓͼ꞉ꜜⱱꞌԜꜛꜛԜᴡ꞉ꜝꜜԓͼԜꜜᴑͼꜞԜ꞉ꜜͼ
ӿⱪᴟԜ꞉ⱲͼᴒᴡͼԜꞌ᷅ԓͼ᷉᷇᷈᷉ⱢͼᴇᴢᴟԜᴤͼᴒᴡͼԜꞌ᷅ԓͼ᷊᷉᷇᷈Ԑ᷅ͼⱷꜜᴡᴒᴟᴣᴒꜜ꞉ꜜⱲͼԜᴡͼᴡⱳᴒͼꞌᴒᴣᴒꞌͼꜝⱱͼԝᴟԜᴑᴦꞋ꞉ꜜ꞉ꜜͼꜞᴟꜝᴑᴢᴐᴡ꞉ꜝꜜͼᴤ꞉ᴡⱳͼԜͼ
ꜞꞌԜᴠꜛԜͼꞋԜꞌꞌ꞉Ꞌᴟᴒ꞉ꜜͼ꞉ꜜⱳ꞉ԝ꞉ᴡꜝᴟͼᴡⱳᴒᴟᴒⱱꜝᴟᴒͼᴟᴒꜞᴟᴒᴠᴒꜜᴡᴠͼԜꜜͼԜᴡᴡᴟԜᴐᴡ꞉ᴣᴒͼԜꜜᴑͼᴟԜᴡ꞉ꜝꜜԜꞌͼᴡⱳᴒᴟԜꜞᴒᴢᴡ꞉ᴐͼᴠᴡᴟԜᴡᴒⱲᴦͼⱱꜝᴟͼ
ⱶⱨⱬ᷅ͼⱷꜜᴑᴒᴒᴑԓͼᴡⱳᴒͼ꞉ꜛꜞꜝᴟᴡԜꜜᴐᴒͼꜝⱱͼꜞꞌԜᴠꜛԜͼꞋԜꞌꞌ꞉Ꞌᴟᴒ꞉ꜜͼԜᴠͼԜͼᴑᴟᴢⱲͼᴡԜᴟⱲᴒᴡͼ꞉ꜜͼⱶⱨⱬͼⱳԜᴠԝᴒᴒꜜͼᴣԜꞌ꞉ᴑԜᴡᴒᴑͼ
ᴡⱳᴟꜝᴢⱲⱳͼᴡⱳᴒͼꜝԝᴠᴒᴟᴣᴒᴑͼᴒⱱⱱᴒᴐᴡ꞉ᴣᴒꜜᴒᴠᴠͼꜝⱱͼꜘԜꞌԝ꞉ᴡꜝᴟᶇӿᴒᴐԜꞌꞌԜꜜᴡ꞉ᴑᴒԐԓͼԜͼꜞᴒꜞᴡ꞉ᴑᴒͼᴡⱳԜᴡͼᴠꜞᴒᴐ꞉ⱱ꞉ᴐԜꞌꞌᴦͼᴡԜᴟⱲᴒᴡᴠͼ
ꜞꞌԜᴠꜛԜͼꞋԜꞌꞌ꞉Ꞌᴟᴒ꞉ꜜԓͼᴤⱳ꞉ᴐⱳͼᴤԜᴠͼԜꜞꜞᴟꜝᴣᴒᴑͼԝᴦͼᴡⱳᴒͼⱴⱫⱨͼⱱꜝᴟͼᴡⱳᴒͼᴡᴟᴒԜᴡꜛᴒꜜᴡͼꜝⱱͼԜᴐᴢᴡᴒͼⱶⱨⱬͼԜᴡᴡԜᴐꞋᴠͼ
ӿꜘԜꞌԝ꞉ᴡꜝᴟᶇ͟ԜᴐꞋԜⱲᴒͼⱷꜜᴠᴒᴟᴡԓͼ᷿᷉᷇᷈Ԑ᷅ͼ
Ⱬᴅ᷄᷉Ⱡ᷊᷇ͼ꞉ᴠͼԜͼⱳ꞉ⱲⱳꞌᴦͼꜞꜝᴡᴒꜜᴡͼԜꜜᴑͼᴠꜞᴒᴐ꞉ⱱ꞉ᴐͼ꞉ꜜⱳ꞉ԝ꞉ᴡꜝᴟͼꜝⱱͼꜞꞌԜᴠꜛԜͼꞋԜꞌꞌ꞉Ꞌᴟᴒ꞉ꜜͼӿꜘ꞉ͼⱤͼ᷿᷈᷉ͼꜞꜚԐ᷅ͼᴅ᷄ᴟԜᴦͼ
ᴐᴟᴦᴠᴡԜꞌꞌꜝⱲᴟԜꜞⱳᴦͼꜝⱱͼⱫᴅ᷄᷉Ⱡ᷊᷇ͼᴐꜝꜛԝ꞉ꜜᴒᴑͼᴤ꞉ᴡⱳͼꜞꞌԜᴠꜛԜͼꞋԜꞌꞌ꞉Ꞌᴟᴒ꞉ꜜͼᴑᴒꜛꜝꜜᴠᴡᴟԜᴡᴒᴠͼⱫᴅ᷄᷉Ⱡ᷊᷇ͼԝ꞉ꜜᴑ꞉ꜜⱲͼᴡꜝͼ
ᴡⱳᴒͼԜᴐᴡ꞉ᴣᴒͼᴠ꞉ᴡᴒͼꜝⱱͼꞋԜꞌꞌ꞉Ꞌᴟᴒ꞉ꜜͼӿꜘᴒꜜꜜ꞉ᴠᴡꜝꜜͼᴒᴡͼԜꞌ᷅ԓͼ᷉᷇᷈᷾Ԑ᷅
1.4
Safety Rationale for DX-2930
ᴀԜⱱᴒᴡᴦͼᴑԜᴡԜͼⱱᴟꜝꜛͼᴡⱳᴒͼ͟ⱳԜᴠᴒͼ᷈Ԝͼᴐꞌ꞉ꜜ꞉ᴐԜꞌͼᴠᴡᴢᴑᴦԓͼԜͼⱱ꞉ᴟᴠᴡ᷄꞉ꜜ᷄ⱳᴢꜛԜꜜͼᴠᴡᴢᴑᴦͼᴤ꞉ᴡⱳͼⱫᴅ᷄᷉Ⱡ᷊᷇ͼ꞉ꜜͼⱳᴒԜꞌᴡⱳᴦͼ
ᴠᴢԝ꞊ᴒᴐᴡᴠͼᴑ꞉ᴑͼꜜꜝᴡͼ꞉ᴑᴒꜜᴡ꞉ⱱᴦͼԜꜜᴦͼᴠԜⱱᴒᴡᴦͼᴐꜝꜜᴐᴒᴟꜜᴠ᷅ͼᴀ꞉ꜜⱲꞌᴒͼᴑꜝᴠᴒᴠͼᴢꜞͼᴡꜝͼ᷊ͼꜛⱲ᷆ꞋⱲͼꜝⱱͼⱫᴅ᷄᷉Ⱡ᷊᷇ͼᴤᴒᴟᴒͼᴤᴒꞌꞌ᷄
ᴡꜝꞌᴒᴟԜᴡᴒᴑ᷅ͼᴁⱳᴒᴟᴒͼᴤᴒᴟᴒͼꜜꜝͼᴑꜝᴠᴒ᷄ꞌ꞉ꜛ꞉ᴡ꞉ꜜⱲᴡꜝᴥ꞉ᴐ꞉ᴡ꞉ᴒᴠԓͼᴠᴒᴟ꞉ꜝᴢᴠͼԜᴑᴣᴒᴟᴠᴒͼᴒᴣᴒꜜᴡᴠԓͼꜝᴟͼԜꜜᴦͼꜝᴡⱳᴒᴟͼᴠԜⱱᴒᴡᴦͼ
ᴐꜝꜜᴐᴒᴟꜜᴠͼ꞉ᴑᴒꜜᴡ꞉ⱱ꞉ᴒᴑ᷅
͟ⱳԜᴟꜛԜᴐꜝꞋ꞉ꜜᴒᴡ꞉ᴐͼӿ͟ꜘԐͼᴑԜᴡԜͼⱱᴟꜝꜛͼᴡⱳᴒͼ͟ⱳԜᴠᴒͼ᷈ԜͼԜꜜᴑͼ᷈ԝͼᴐꞌ꞉ꜜ꞉ᴐԜꞌͼᴠᴡᴢᴑ꞉ᴒᴠͼ꞉ꜜͼᴐꜝꜜ꞊ᴢꜜᴐᴡ꞉ꜝꜜͼᴤ꞉ᴡⱳͼᴑԜᴡԜͼ
ⱱᴟꜝꜛͼᴡⱳᴒͼꜜꜝꜜᴐꞌ꞉ꜜ꞉ᴐԜꞌͼᴡꜝᴥ꞉ᴐ꞉ᴡᴦͼᴠᴡᴢᴑ꞉ᴒᴠͼᴠᴢꜞꜞꜝᴟᴡͼԜͼᴤ꞉ᴑᴒͼᴠԜⱱᴒᴡᴦͼꜛԜᴟⱲ꞉ꜜ᷅ͼᴁⱳᴒͼꜛᴒԜꜜͼⱪꜛԜᴥⱱꜝᴟⱳᴢꜛԜꜜͼ
ᴠᴢԝ꞊ᴒᴐᴡᴠͼᴡᴟᴒԜᴡᴒᴑͼԜᴡͼԜͼᴑꜝᴠᴒͼꜝⱱͼ᷊᷇᷇ͼꜛⱲͼꜝꜜͼⱫԜᴦᴠͼ᷈ͼԜꜜᴑͼ᷿᷈ͼᴤԜᴠͼԜꜞꜞᴟꜝᴥ꞉ꜛԜᴡᴒꞌᴦͼ᷉ⅎͼⱲ᷆ꜛꜙ᷅ͼⱨᴠͼ
ᴐꜝꜛꜞԜᴟ꞉ᴠꜝꜜԓͼԜͼꜛᴒԜꜜͼⱪꜛԜᴥꜝⱱͼⅎ᷾᷾ͼⱲͼ᷆ꜛꜙͼᴤԜᴠͼꜝԝᴠᴒᴟᴣᴒᴑͼⱱꜝꞌꞌꜝᴤ꞉ꜜⱲͼᴑꜝᴠ꞉ꜜⱲͼꜝⱱͼꜛꜝꜜꞋᴒᴦᴠͼᴤ꞉ᴡⱳͼ
᷿᷇ꜛⱲ᷆ꞋⱲͼⱫᴅ᷄᷉Ⱡ᷊᷇ͼᴀⱪͼᴤᴒᴒꞋꞌᴦͼⱱꜝᴟͼ⅍ͼꜛꜝꜜᴡⱳᴠͼᴟᴒᴠᴢꞌᴡ꞉ꜜⱲͼ꞉ꜜͼԜͼᴠԜⱱᴒᴡᴦͼꜛԜᴟⱲ꞉ꜜͼꜝⱱͼԜꜞꜞᴟꜝᴥ꞉ꜛԜᴡᴒꞌᴦͼ᷉˲᷄
ⱱꜝꞌᴑ᷅ͼ꜠ꜝͼᴡꜝᴥ꞉ᴐꜝꞌꜝⱲ꞉ᴐԜꞌꞌᴦͼᴠ꞉Ⱳꜜ꞉ⱱ꞉ᴐԜꜜᴡͼⱱ꞉ꜜᴑ꞉ꜜⱲᴠͼᴤᴒᴟᴒͼꜝԝᴠᴒᴟᴣᴒᴑͼ꞉ꜜͼᴡⱳᴒᴠᴒͼᴡᴟᴒԜᴡᴒᴑͼԜꜜ꞉ꜛԜꞌᴠͼꜝᴟͼ꞉ꜜͼԜꜜᴦͼ
ꜝᴡⱳᴒᴟͼꜜꜝꜜᴐꞌ꞉ꜜ꞉ᴐԜꞌͼᴡꜝᴥ꞉ᴐ꞉ᴡᴦͼᴠᴡᴢᴑᴦͼᴡꜝͼᴑԜᴡᴒͼⱱꜝᴟͼᴠᴦᴠᴡᴒꜛ꞉ᴐԜꞌꞌᴦͼԜᴑꜛ꞉ꜜ꞉ᴠᴡᴒᴟᴒᴑͼⱫᴅ᷄᷉Ⱡ᷊᷇᷅
ᴀԜⱱᴒᴡᴦͼᴑԜᴡԜͼ꞉ᴠͼԜꞌᴠꜝͼԜᴣԜ꞉ꞌԜԝꞌᴒͼⱱᴟꜝꜛͼᴡⱳᴒͼ͟ⱳԜᴠᴒͼ᷈ԝͼᴠᴡᴢᴑᴦԓͼԜͼꜛᴢꞌᴡ꞉ꜞꞌᴒ᷄Ԝᴠᴐᴒꜜᴑ꞉ꜜⱲͼᴑꜝᴠᴒͼᴠᴡᴢᴑᴦͼ꞉ꜜͼⱶⱨⱬͼ
ꜞԜᴡ꞉ᴒꜜᴡᴠ᷅ͼⱷꜜͼᴡⱳ꞉ᴠͼᴠᴡᴢᴑᴦԓͼᴡᴤꜝͼᴑꜝᴠᴒᴠͼꜝⱱͼⱫᴅ᷄᷉Ⱡ᷊᷇ͼᴢꜞͼᴡꜝͼ᷾᷇᷇ͼꜛⱲͼԜᴑꜛ꞉ꜜ꞉ᴠᴡᴒᴟᴒᴑͼ᷈᷾ͼᴑԜᴦᴠͼԜꜞԜᴟᴡͼᴤᴒᴟᴒͼ
ᴤᴒꞌꞌ᷄ᴡꜝꞌᴒᴟԜᴡᴒᴑ᷅ͼᴁⱳᴒᴟᴒͼᴤᴒᴟᴒͼꜜꜝͼᴑꜝᴠᴒ᷄ꞌ꞉ꜛ꞉ᴡ꞉ꜜⱲͼᴡꜝᴥ꞉ᴐ꞉ᴡ꞉ᴒᴠԓͼᴠᴒᴟ꞉ꜝᴢᴠͼԜᴑᴣᴒᴟᴠᴒͼᴒᴣᴒꜜᴡᴠͼ꞉ꜜͼԜꜜᴦͼⱫᴅ᷄᷉Ⱡ᷊᷇ͼ
ᴡᴟᴒԜᴡᴒᴑͼᴠᴢԝ꞊ᴒᴐᴡᴠԓͼꜝᴟͼԜꜜᴦͼꜝᴡⱳᴒᴟͼᴠԜⱱᴒᴡᴦͼᴐꜝꜜᴐᴒᴟꜜᴠͼ꞉ᴑᴒꜜᴡ꞉ⱱ꞉ᴒᴑͼ꞉ꜜͼᴡⱳ꞉ᴠͼᴠᴡᴢᴑᴦͼꜝⱱͼⱶⱨⱬͼꜞԜᴡ꞉ᴒꜜᴡᴠ᷅ͼ
͟ⱳԜᴟꜛԜᴐꜝꞋ꞉ꜜᴒᴡ꞉ᴐͼᴑԜᴡԜͼⱱᴟꜝꜛͼᴡⱳᴒͼ᷈ԝͼᴠᴡᴢᴑᴦͼⱱꜝᴢꜜᴑͼᴡⱳԜᴡͼᴡⱳᴒͼᴑᴟᴢⱲͼᴒᴥꜞꜝᴠᴢᴟᴒͼⱱꜝꞌꞌꜝᴤ꞉ꜜⱲͼᴡᴤꜝͼ
Ԝᴑꜛ꞉ꜜ꞉ᴠᴡᴟԜᴡ꞉ꜝꜜᴠͼꜝⱱͼⱫᴅ᷄᷉Ⱡ᷊᷇ͼӿᴢꜞͼᴡꜝͼԜͼꜛԜᴥ꞉ꜛᴢꜛͼꜝⱱͼ᷾᷇᷇ͼꜛⱲԐͼᴤԜᴠͼᴠᴢԝᴠᴡԜꜜᴡ꞉ԜꞌꞌᴦͼꞌᴒᴠᴠͼᴡⱳԜꜜͼᴡⱳԜᴡͼ
ԜᴡᴡԜ꞉ꜜᴒᴑͼԜꜜᴑͼᴒᴣԜꞌᴢԜᴡᴒᴑͼ꞉ꜜͼᴡⱳᴒͼꜜꜝꜜᴐꞌ꞉ꜜ꞉ᴐԜꞌͼᴡꜝᴥ꞉ᴐ꞉ᴡᴦͼᴠᴡᴢᴑ꞉ᴒᴠ᷅
ⱴꜝᴟͼԜᴑᴑ꞉ᴡ꞉ꜝꜜԜꞌͼᴑᴒᴡԜ꞉ꞌͼᴟᴒⱲԜᴟᴑ꞉ꜜⱲͼᴡⱳᴒͼᴠԜⱱᴒᴡᴦͼᴟԜᴡ꞉ꜝꜜԜꞌᴒͼⱱꜝᴟͼⱫᴅ᷄᷉Ⱡ᷊᷇ԓͼꜞꞌᴒԜᴠᴒͼᴟᴒⱱᴒᴟͼᴡꜝͼᴡⱳᴒͼⱫᴅ᷄᷉Ⱡ᷊᷇ͼ
ⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟᶳᴠͼⱩᴟꜝᴐⱳᴢᴟᴒ᷅
1.5
DX-2930 Non-Clinical Pharmacology and Toxicology
ⱴꜝᴟͼᴑᴒᴡԜ꞉ꞌͼᴟᴒⱲԜᴟᴑ꞉ꜜⱲͼᴡⱳᴒͼꜜꜝꜜᴐꞌ꞉ꜜ꞉ᴐԜꞌͼⱱ꞉ꜜᴑ꞉ꜜⱲᴠԓ ꜞꞌᴒԜᴠᴒͼᴟᴒⱱᴒᴟͼᴡꜝͼᴡⱳᴒͼⱫᴅ᷄᷉Ⱡ᷊᷇ͼⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟᶳᴠͼ
Ⱪᴟꜝᴐⱳᴢᴟᴒ᷅
1.6
DX-2930 Clinical Data
ᴁⱳᴒͼᴐꞌ꞉ꜜ꞉ᴐԜꞌͼᴑᴒᴣᴒꞌꜝꜞꜛᴒꜜᴡͼꜞᴟꜝⱲᴟԜꜛͼᴡꜝͼᴑԜᴡᴒͼⱱꜝᴟͼⱫᴅ᷄᷉Ⱡ᷊᷇ͼᴐꜝꜜᴠ꞉ᴠᴡᴠͼꜝⱱͼ᷉ͼᴠᴡᴢᴑ꞉ᴒᴠͼᴡꜝͼᴒᴣԜꞌᴢԜᴡᴒͼᴡⱳᴒͼ
ᴠԜⱱᴒᴡᴦԓͼᴡꜝꞌᴒᴟԜԝ꞉ꞌ꞉ᴡᴦԓͼԜꜜᴑͼ͟ꜘͼꜝⱱͼⱫᴅ᷄᷉Ⱡ᷊᷇ԓͼ꞉ꜜᴐꞌᴢᴑ꞉ꜜⱲͼԜͼ͟ⱳԜᴠᴒͼ᷈Ԝ ᴠ꞉ꜜⱲꞌᴒ᷄Ԝᴠᴐᴒꜜᴑ꞉ꜜⱲͼᴑꜝᴠᴒͼᴠᴡᴢᴑᴦͼ꞉ꜜͼ

Ⱬᴅ᷄᷉Ⱡ᷊᷇
ⱪꞌ꞉ꜜ꞉ᴐԜꞌͼᴁᴟ꞉Ԝꞌͼ͟ᴟꜝᴡꜝᴐꜝꞌⱡͼⱫᴅ᷄᷉Ⱡ᷊᷊᷇᷄᷇
ⱨꜛᴒꜜᴑꜛᴒꜜᴡͼ᷊᷅᷇ͼⱴ꞉ꜜԜꞌⱡͼ᷇ⱠͼꜗԜꜜᴢԜᴟᴦ᷉᷇᷈ⅎ
ⱪꜝꜜⱱ꞉ᴑᴒꜜᴡ꞉Ԝꞌ
͟ԜⱲᴒͼ᷊᷾
ⱫᴦԜᴥͼⱪꜝᴟꜞ᷅
ⱳᴒԜꞌᴡⱳᴦͼᴠᴢԝ꞊ᴒᴐᴡᴠͼԜꜜᴑͼԜͼ͟ⱳԜᴠᴒͼ᷈ԝͼꜛᴢꞌᴡ꞉ꜞꞌᴒ᷄Ԝᴠᴐᴒꜜᴑ꞉ꜜⱲͼᴑꜝᴠᴒͼᴠᴡᴢᴑᴦͼ꞉ꜜͼⱶⱨⱬͼꜞԜᴡ꞉ᴒꜜᴡᴠ᷅ͼᴁⱳᴒᴠᴒͼᴠᴡᴢᴑ꞉ᴒᴠͼ
ԜᴟᴒͼᴠᴢꜛꜛԜᴟ꞉ᴧᴒᴑͼ꞉ꜜͼᴡⱳᴒͼⱱꜝꞌꞌꜝᴤ꞉ꜜⱲͼᴠᴒᴐᴡ꞉ꜝꜜᴠ᷅
1.6.1
Single-Ascending Dose Study in Healthy Subjects (DX-2930-01)
Ⱬᴅ᷄᷉Ⱡ᷊᷇᷄᷇᷈ͼᴤԜᴠͼԜͼ͟ⱳԜᴠᴒͼ᷈ԜͼᴟԜꜜᴑꜝꜛ꞉ᴧᴒᴑԓͼᴑꜝᴢԝꞌᴒ᷄ԝꞌ꞉ꜜᴑԓͼꜞꞌԜᴐᴒԝꜝ᷄ᴐꜝꜜᴡᴟꜝꞌꞌᴒᴑͼᴠᴡᴢᴑᴦͼ꞉ꜜͼⱳᴒԜꞌᴡⱳᴦͼ
ᴠᴢԝ꞊ᴒᴐᴡᴠͼᴡꜝͼᴒᴣԜꞌᴢԜᴡᴒͼᴡⱳᴒͼᴠԜⱱᴒᴡᴦԓͼᴡꜝꞌᴒᴟԜԝ꞉ꞌ꞉ᴡᴦԓͼԜꜜᴑͼ͟ꜘͼⱱꜝꞌꞌꜝᴤ꞉ꜜⱲͼԜͼᴠ꞉ꜜⱲꞌᴒԓͼᴀⱪͼᴑꜝᴠᴒͼꜝⱱͼⱫᴅ᷄᷉Ⱡ᷊᷇᷅ͼ
͟Ԝᴟᴡ꞉ᴐ꞉ꜞԜᴡ꞉ꜜⱲͼᴠᴢԝ꞊ᴒᴐᴡᴠͼᴤᴒᴟᴒͼᴟԜꜜᴑꜝꜛ꞉ᴧᴒᴑͼᴡꜝͼᴟᴒᴐᴒ꞉ᴣᴒͼꜞꞌԜᴐᴒԝꜝͼꜝᴟͼԜᴐᴡ꞉ᴣᴒͼᴠᴡᴢᴑᴦͼᴑᴟᴢⱲͼᴤ꞉ᴡⱳ꞉ꜜͼꜝꜜᴒͼꜝⱱͼᴡⱳᴒͼ
ⱱꜝꞌꞌꜝᴤ꞉ꜜⱲͼᴠᴒꜟᴢᴒꜜᴡ꞉ԜꞌԓͼԜᴠᴐᴒꜜᴑ꞉ꜜⱲͼᴑꜝᴠᴒͼᴐꜝⱳꜝᴟᴡᴠⱡͼ᷇᷅᷈ԓͼ᷊᷇᷅ԓͼ᷈᷅᷇ԓͼꜝᴟͼ᷊᷅᷇ͼꜛⱲ᷆ꞋⱲ᷅ͼⱴꜝᴟͼᴒԜᴐⱳͼᴑꜝᴠ꞉ꜜⱲͼᴐꜝⱳꜝᴟᴡԓͼ
⅍ͼᴠᴢԝ꞊ᴒᴐᴡᴠͼᴤᴒᴟᴒͼᴟԜꜜᴑꜝꜛ꞉ᴧᴒᴑͼᴡꜝͼᴟᴒᴐᴒ꞉ᴣᴒͼԜᴐᴡ꞉ᴣᴒͼᴑᴟᴢⱲͼԜꜜᴑͼ᷉ͼᴠᴢԝ꞊ᴒᴐᴡᴠͼᴡꜝͼᴟᴒᴐᴒ꞉ᴣᴒͼꜞꞌԜᴐᴒԝꜝ᷅ͼ
ⱨͼᴡꜝᴡԜꞌͼꜝⱱͼ᷊᷉ͼᴠᴢԝ꞊ᴒᴐᴡᴠͼᴒꜜᴟꜝꞌꞌᴒᴑͼ꞉ꜜͼᴡⱳᴒͼᴠᴡᴢᴑᴦͼԜꜜᴑͼᴤᴒᴟᴒͼᴟԜꜜᴑꜝꜛ꞉ᴧᴒᴑ᷅ͼᴁⱳᴒͼᴡᴟᴒԜᴡꜛᴒꜜᴡͼⱲᴟꜝᴢꜞᴠͼᴤᴒᴟᴒͼ
ᴤᴒꞌꞌͼԝԜꞌԜꜜᴐᴒᴑͼⱱꜝᴟͼᴑᴒꜛꜝⱲᴟԜꜞⱳ꞉ᴐͼᴐⱳԜᴟԜᴐᴡᴒᴟ꞉ᴠᴡ꞉ᴐᴠ᷅ͼᴁⱳᴒͼԜᴐᴡᴢԜꞌͼᴑꜝᴠᴒͼꜝⱱͼⱫᴅ᷄᷉Ⱡ᷊᷇ͼԜᴑꜛ꞉ꜜ꞉ᴠᴡᴒᴟᴒᴑͼᴡꜝͼ
ᴠᴢԝ꞊ᴒᴐᴡᴠͼᴟԜꜜⱲᴒᴑͼⱱᴟꜝꜛͼ⅍᷅᷉ꜛⱲͼӿ꞉ꜜͼᴡⱳᴒͼ᷇᷅᷈ͼꜛⱲ᷆ꞋⱲͼⱲᴟꜝᴢꜞԐͼᴡꜝͼ᷊᷇᷇ͼꜛⱲͼӿ꞉ꜜͼᴡⱳᴒͼ᷊᷅᷇ͼꜛⱲ᷆ꞋⱲͼⱲᴟꜝᴢꜞԐͼԜᴐᴟꜝᴠᴠͼ
Ԝꞌꞌͼᴐꜝⱳꜝᴟᴡᴠ᷅
ⱩԜᴠᴒᴑͼꜝꜜͼᴡⱳᴒͼᴠԜⱱᴒᴡᴦͼԜꜜԜꞌᴦᴠ꞉ᴠԓͼԜͼᴠ꞉ꜜⱲꞌᴒͼԜᴑꜛ꞉ꜜ꞉ᴠᴡᴟԜᴡ꞉ꜝꜜͼꜝⱱͼⱫᴅ᷄᷉Ⱡ᷊᷇ͼᴤԜᴠͼᴤᴒꞌꞌͼᴡꜝꞌᴒᴟԜᴡᴒᴑͼᴢꜞͼᴡꜝͼᴑꜝᴠᴒᴠͼ
ꜝⱱͼ᷊᷅᷇ͼꜛⱲ᷆ꞋⱲͼᴤ꞉ᴡⱳꜝᴢᴡͼᴒᴣ꞉ᴑᴒꜜᴐᴒͼꜝⱱͼᴑꜝᴠᴒ᷄ꞌ꞉ꜛ꞉ᴡ꞉ꜜⱲͼᴡꜝᴥ꞉ᴐ꞉ᴡᴦ᷅ͼᴁⱳᴒᴟᴒͼᴤᴒᴟᴒͼꜜꜝͼᴑᴒԜᴡⱳᴠԓͼᴀⱨⱬᴠԓͼꜝᴟͼᴠᴢԝ꞊ᴒᴐᴡͼ
ᴑ꞉ᴠᴐꜝꜜᴡ꞉ꜜᴢԜᴡ꞉ꜝꜜᴠͼᴑᴢᴒͼᴡꜝͼԜᴑᴣᴒᴟᴠᴒͼᴒᴣᴒꜜᴡᴠͼӿⱨⱬᴠԐͼᴑᴢᴟ꞉ꜜⱲͼᴡⱳᴒͼᴠᴡᴢᴑᴦ᷅ͼⱴᴢᴟᴡⱳᴒᴟꜛꜝᴟᴒԓͼᴡⱳᴒᴟᴒͼᴤԜᴠͼꜜꜝͼ
ᴠ꞉Ⱳꜜ꞉ⱱ꞉ᴐԜꜜᴡͼ꞉ꜛԝԜꞌԜꜜᴐᴒͼԝᴒᴡᴤᴒᴒꜜͼꜞꞌԜᴐᴒԝꜝͼԜꜜᴑͼⱫᴅ᷄᷉Ⱡ᷊᷇ͼⱱꜝᴟͼԜꜜᴦͼꜞԜᴟᴡ꞉ᴐᴢꞌԜᴟͼᴡᴟᴒԜᴡꜛᴒꜜᴡ᷄ᴒꜛᴒᴟⱲᴒꜜᴡͼ
ԜᴑᴣᴒᴟᴠᴒͼᴒᴣᴒꜜᴡͼӿᴁⱬⱨⱬԐ᷅ͼᴁⱳᴒͼꜛꜝᴠᴡͼᴐꜝꜛꜛꜝꜜꞌᴦͼᴟᴒꜞꜝᴟᴡᴒᴑͼᴁⱬⱨⱬͼᴤԜᴠͼⱳᴒԜᴑԜᴐⱳᴒԓͼᴤⱳ꞉ᴐⱳͼꜝᴐᴐᴢᴟᴟᴒᴑͼԜᴡͼԜͼ
ᴟԜᴡᴒͼꜝⱱͼ᷿᷉ӼͼⱱꜝᴟͼԝꜝᴡⱳͼⱫᴅ᷄᷉Ⱡ᷊᷇ͼԜꜜᴑͼꜞꞌԜᴐᴒԝꜝ᷅
ᴁⱳᴒͼ͟ꜘͼꜞᴟꜝⱱ꞉ꞌᴒͼᴑᴒꜛꜝꜜᴠᴡᴟԜᴡᴒᴑͼꞌ꞉ꜜᴒԜᴟԓͼᴑꜝᴠᴒ᷄ᴑᴒꜞᴒꜜᴑᴒꜜᴡͼᴑᴟᴢⱲͼᴒᴥꜞꜝᴠᴢᴟᴒͼᴤ꞉ᴡⱳͼԜͼꜛᴒԜꜜͼⱳԜꞌⱱ᷄ꞌ꞉ⱱᴒͼꜝⱱͼ
Ԝꜞꜞᴟꜝᴥ꞉ꜛԜᴡᴒꞌᴦͼ᷈ⅎͼᴡꜝͼ᷉᷈ͼᴑԜᴦᴠͼԜᴐᴟꜝᴠᴠͼᴑꜝᴠᴒͼⱲᴟꜝᴢꜞᴠ᷅ͼϸᴒᴠᴢꞌᴡᴠͼⱱᴟꜝꜛͼᴡᴤꜝͼᴒᴥꜞꞌꜝᴟԜᴡꜝᴟᴦͼԝ꞉ꜝꜛԜᴟꞋᴒᴟͼԜᴠᴠԜᴦᴠͼ
ꜞᴟꜝᴣ꞉ᴑᴒͼᴒᴣ꞉ᴑᴒꜜᴐᴒͼⱱꜝᴟͼԜꜜͼ꞉ꜛꜞꜝᴟᴡԜꜜᴡͼꜞⱳԜᴟꜛԜᴐꜝᴑᴦꜜԜꜛ꞉ᴐͼᴒⱱⱱᴒᴐᴡͼꜝⱱͼⱫᴅ᷄᷉Ⱡ᷊᷇ͼ꞉ꜜͼⱳᴢꜛԜꜜᴠ᷅ͼ
ⱴꜝᴟͼԜᴑᴑ꞉ᴡ꞉ꜝꜜԜꞌͼᴑᴒᴡԜ꞉ꞌͼᴟᴒⱲԜᴟᴑ꞉ꜜⱲͼᴡⱳᴒͼᴠ꞉ꜜⱲꞌᴒͼᴑꜝᴠᴒԓͼᴐꞌ꞉ꜜ꞉ᴐԜꞌͼᴠᴡᴢᴑᴦͼ꞉ꜜͼⱳᴒԜꞌᴡⱳᴦͼᴠᴢԝ꞊ᴒᴐᴡᴠԓͼꜞꞌᴒԜᴠᴒͼᴟᴒⱱᴒᴟͼᴡꜝͼ
ᴡⱳᴒͼⱫᴅ᷄᷉Ⱡ᷊᷇ͼⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟᶳᴠͼⱩᴟꜝᴐⱳᴢᴟᴒ᷅
1.6.2
Multiple-Ascending Dose Study in HAE Patients (DX-2930-02)
Ⱬᴅ᷄᷉Ⱡ᷊᷇᷄᷇᷉ͼᴤԜᴠͼԜͼ͟ⱳԜᴠᴒͼ᷈ԝͼᴟԜꜜᴑꜝꜛ꞉ᴧᴒᴑԓͼᴑꜝᴢԝꞌᴒ᷄ԝꞌ꞉ꜜᴑԓͼꜞꞌԜᴐᴒԝꜝ᷄ᴐꜝꜜᴡᴟꜝꞌꞌᴒᴑԓͼꜛᴢꞌᴡ꞉ꜞꞌᴒͼԜᴠᴐᴒꜜᴑ꞉ꜜⱲ᷄
ᴑꜝᴠᴒͼᴠᴡᴢᴑᴦͼ꞉ꜜͼꜞԜᴡ꞉ᴒꜜᴡᴠͼᴤ꞉ᴡⱳͼⱶⱨⱬͼᴡꜝͼᴒᴣԜꞌᴢԜᴡᴒͼᴠԜⱱᴒᴡᴦԓͼᴡꜝꞌᴒᴟԜԝ꞉ꞌ꞉ᴡᴦԓͼԜꜜᴑͼ͟ꜘͼꜝⱱͼᴀⱪͼⱫᴅ᷄᷉Ⱡ᷊᷇᷅ͼ
͟Ԝᴟᴡ꞉ᴐ꞉ꜞԜᴡ꞉ꜜⱲͼᴠᴢԝ꞊ᴒᴐᴡᴠͼᴤᴒᴟᴒͼᴟԜꜜᴑꜝꜛ꞉ᴧᴒᴑͼ᷉ⱡ᷈ͼᴡꜝͼᴟᴒᴐᴒ꞉ᴣᴒͼᴒ꞉ᴡⱳᴒᴟͼԜᴐᴡ꞉ᴣᴒͼᴠᴡᴢᴑᴦͼᴑᴟᴢⱲͼꜝᴟͼꜞꞌԜᴐᴒԝꜝͼᴤ꞉ᴡⱳ꞉ꜜͼ
ꜝꜜᴒͼꜝⱱͼᴡⱳᴒͼⱱꜝꞌꞌꜝᴤ꞉ꜜⱲͼᴠᴒꜟᴢᴒꜜᴡ꞉ԜꞌԓͼԜᴠᴐᴒꜜᴑ꞉ꜜⱲͼᴑꜝᴠᴒͼᴐꜝⱳꜝᴟᴡᴠⱡͼ᷊᷇ԓͼ᷈᷇᷇ԓͼ᷊᷇᷇ԓͼꜝᴟͼ᷾᷇᷇ꜛⱲͼӿꜜꜝꜛ꞉ꜜԜꞌͼ⅍ͼ
ᴠᴢԝ꞊ᴒᴐᴡᴠͼꜞᴒᴟͼᴐꜝⱳꜝᴟᴡԐ᷅ͼⱬԜᴐⱳͼᴠᴢԝ꞊ᴒᴐᴡͼᴟᴒᴐᴒ꞉ᴣᴒᴑͼ᷉ͼᴑꜝᴠᴒᴠͼꜝⱱͼᴠᴡᴢᴑᴦͼᴑᴟᴢⱲͼᴠᴒꜞԜᴟԜᴡᴒᴑͼԝᴦͼ᷈᷾ͼᴑԜᴦᴠͼԜꜜᴑͼᴤᴒᴟᴒͼ
ⱱꜝꞌꞌꜝᴤᴒᴑͼⱱꜝᴟͼ᷿᷈ͼᴤᴒᴒꞋᴠͼԜⱱᴡᴒᴟͼᴡⱳᴒͼᴠᴒᴐꜝꜜᴑͼᴑꜝᴠᴒ᷅ͼ
ⱨͼᴡꜝᴡԜꞌͼꜝⱱͼ᷊ⅎͼᴠᴢԝ꞊ᴒᴐᴡᴠͼᴤᴒᴟᴒͼᴟԜꜜᴑꜝꜛ꞉ᴧᴒᴑͼԜꜜᴑͼᴡᴟᴒԜᴡᴒᴑͼᴤ꞉ᴡⱳͼⱫᴅ᷄᷉Ⱡ᷊᷇ͼꜝᴟͼꜞꞌԜᴐᴒԝꜝ᷅ͼ꜡ꜜᴒͼᴠᴢԝ꞊ᴒᴐᴡͼ꞉ꜜͼᴡⱳᴒͼ
᷾᷇᷇ͼꜛⱲͼᴑꜝᴠᴒͼⱲᴟꜝᴢꜞͼᴟᴒᴐᴒ꞉ᴣᴒᴑͼԜͼᴠ꞉ꜜⱲꞌᴒͼᴑꜝᴠᴒͼꜝⱱͼⱫᴅ᷄᷉Ⱡ᷊᷇ͼԜꜜᴑԓͼⱱꜝꞌꞌꜝᴤ꞉ꜜⱲͼᴠᴒᴣᴒᴟԜꞌͼᴢꜜᴠᴢᴐᴐᴒᴠᴠⱱᴢꞌͼ
Ԝᴡᴡᴒꜛꜞᴡᴠͼᴡꜝͼᴠᴐⱳᴒᴑᴢꞌᴒͼᴡⱳᴒ꞉ᴟͼᴠᴒᴐꜝꜜᴑͼᴑꜝᴠᴒԓͼᴤԜᴠͼᴟᴒꜞꞌԜᴐᴒᴑ᷅ͼᴁⱳ꞉ᴠͼᴠᴢԝ꞊ᴒᴐᴡͼᴟᴒᴡᴢᴟꜜᴒᴑͼⱱꜝᴟͼԜͼᴠ꞉ꜜⱲꞌᴒͼⱱꜝꞌꞌꜝᴤ᷄ᴢꜞͼ
ᴣ꞉ᴠ꞉ᴡͼԝᴒⱱꜝᴟᴒͼԝᴒ꞉ꜜⱲͼꞌꜝᴠᴡͼᴡꜝͼⱱꜝꞌꞌꜝᴤ᷄ᴢꜞͼⱱꜝᴟͼᴟᴒԜᴠꜝꜜᴠͼꜜꜝᴡͼᴟᴒꞌԜᴡᴒᴑͼᴡꜝͼᴡⱳᴒͼᴠᴡᴢᴑᴦ᷅ͼϸꜝᴢᴡ꞉ꜜᴒͼⱪ᷈᷄ⱷ꜠ⱶͼᴡᴒᴠᴡ꞉ꜜⱲͼ
ᴟᴒᴣᴒԜꞌᴒᴑͼᴡⱳԜᴡͼꜝꜜᴒͼꜝᴡⱳᴒᴟͼᴠᴢԝ꞊ᴒᴐᴡͼᴑ꞉ᴑͼꜜꜝᴡͼⱳԜᴣᴒͼⱶⱨⱬͼᴁᴦꜞᴒͼⱷͼꜝᴟͼⱷⱷԓͼᴑᴒᴠꜞ꞉ᴡᴒͼԜͼⱳ꞉ᴠᴡꜝᴟ꞉ᴐԜꞌͼꞌԜԝͼᴡᴒᴠᴡͼ
꞉ꜜᴑ꞉ᴐԜᴡ꞉ꜜⱲͼꜝᴡⱳᴒᴟᴤ꞉ᴠᴒ᷅

Ⱬᴅ᷄᷉Ⱡ᷊᷇
ⱪꞌ꞉ꜜ꞉ᴐԜꞌͼᴁᴟ꞉Ԝꞌͼ͟ᴟꜝᴡꜝᴐꜝꞌⱡͼⱫᴅ᷄᷉Ⱡ᷊᷊᷇᷄᷇
ⱨꜛᴒꜜᴑꜛᴒꜜᴡͼ᷊᷅᷇ͼⱴ꞉ꜜԜꞌⱡͼ᷇ⱠͼꜗԜꜜᴢԜᴟᴦ᷉᷇᷈ⅎ
ⱪꜝꜜⱱ꞉ᴑᴒꜜᴡ꞉Ԝꞌ
͟ԜⱲᴒͼ᷊᷿
ⱫᴦԜᴥͼⱪꜝᴟꜞ᷅
ᴀᴢԝ꞊ᴒᴐᴡͼᴑᴒꜛꜝⱲᴟԜꜞⱳ꞉ᴐᴠͼᴤᴒᴟᴒͼԝԜꞌԜꜜᴐᴒᴑͼ꞉ꜜͼᴡᴒᴟꜛᴠͼꜝⱱͼԜⱲᴒԓͼᴟԜᴐᴒԓͼᴒᴡⱳꜜ꞉ᴐ꞉ᴡᴦͼԜꜜᴑͼⱩꜚⱷ᷅ͼᴁⱳᴒᴟᴒͼᴤᴒᴟᴒͼ
ᴠꞌ꞉ⱲⱳᴡꞌᴦͼꜛꜝᴟᴒͼⱱᴒꜛԜꞌᴒᴠͼ꞉ꜜͼᴡⱳᴒͼⱫᴅ᷄᷉Ⱡ᷊᷇ͼⱲᴟꜝᴢꜞͼᴡⱳԜꜜͼ꞉ꜜͼᴡⱳᴒͼꜞꞌԜᴐᴒԝꜝͼⱲᴟꜝᴢꜞͼӿ⅍⅍᷅ⅎӼͼᴣᴒᴟᴠᴢᴠͼ᷿᷊᷅˲ӼԐ᷅ͼ
ᴁⱳᴒͼꜛꜝᴠᴡͼᴐꜝꜛꜛꜝꜜͼⱨⱬᴠͼᴟᴒꜞꜝᴟᴡᴒᴑͼᴤᴒᴟᴒͼⱶⱨⱬͼԜᴡᴡԜᴐꞋᴠԓͼ꞉ꜜ꞊ᴒᴐᴡ꞉ꜝꜜͼᴠ꞉ᴡᴒͼꜞԜ꞉ꜜԓͼԜꜜᴑͼⱳᴒԜᴑԜᴐⱳᴒ᷅ͼᴁⱳᴒͼᴟԜᴡᴒᴠ
ᴤᴒᴟᴒͼꜜꜝᴡͼԜꜞꜞᴟᴒᴐ꞉Ԝԝꞌᴦͼⱳ꞉Ⱳⱳᴒᴟͼ꞉ꜜͼᴡⱳᴒͼⱫᴅ᷄᷉Ⱡ᷊᷇ͼᴠᴢԝ꞊ᴒᴐᴡᴠͼᴐꜝꜛꜞԜᴟᴒᴑͼᴡꜝͼꜞꞌԜᴐᴒԝꜝ᷅ͼᴁᴤꜝͼᴠᴢԝ꞊ᴒᴐᴡᴠͼᴤᴒᴟᴒͼ
ᴟᴒꜞꜝᴟᴡᴒᴑͼᴡꜝͼⱳԜᴣᴒͼ᷊ͼᴟᴒꞌԜᴡᴒᴑͼᴠᴒᴣᴒᴟᴒͼᴁⱬⱨⱬᴠ᷅ͼ꜡ꜜᴒͼꜝⱱͼᴡⱳᴒᴠᴒͼᴤԜᴠͼԜͼⱫᴅ᷄᷉Ⱡ᷊᷇ͼᴠᴢԝ꞊ᴒᴐᴡͼӿ᷊᷇ͼꜛⱲԐͼᴤ꞉ᴡⱳͼ
꞉ꜜ꞊ᴒᴐᴡ꞉ꜝꜜͼᴠ꞉ᴡᴒͼꜞԜ꞉ꜜͼꞌԜᴠᴡ꞉ꜜⱲͼ᷈ͼꜛ꞉ꜜᴢᴡᴒͼԜꜜᴑͼꜝꜜᴒͼᴤԜᴠͼԜͼⱫᴅ᷄᷉Ⱡ᷊᷇ͼᴠᴢԝ꞊ᴒᴐᴡͼӿ᷾᷇᷇ͼꜛⱲԐ ᴤ꞉ᴡⱳͼᴤꜝᴟᴠᴒꜜ꞉ꜜⱲͼ
ⱳᴒԜᴑԜᴐⱳᴒͼꞌԜᴠᴡ꞉ꜜⱲͼ᷈ͼꜛ꞉ꜜᴢᴡᴒͼԜꜜᴑͼꜜ꞉ⱲⱳᴡͼᴠᴤᴒԜᴡᴠ᷅
꜠ꜝͼᴠԜⱱᴒᴡᴦͼᴠ꞉ⱲꜜԜꞌᴠͼᴤᴒᴟᴒͼ꞉ᴑᴒꜜᴡ꞉ⱱ꞉ᴒᴑͼⱱꜝᴟͼᴣ꞉ᴡԜꞌͼᴠ꞉Ⱳꜜᴠԓͼꜞⱳᴦᴠ꞉ᴐԜꞌͼᴒᴥԜꜛ꞉ꜜԜᴡ꞉ꜝꜜᴠԓͼᴐꞌ꞉ꜜ꞉ᴐԜꞌͼꞌԜԝꜝᴟԜᴡꜝᴟᴦͼᴡᴒᴠᴡᴠԓͼ
ꜝᴟͼᴒꞌᴒᴐᴡᴟꜝᴐԜᴟᴑ꞉ꜝⱲᴟԜꜛᴠͼӿⱬⱪⱵԐ᷅ͼϸᴒᴠᴢꞌᴡᴠͼᴠᴢⱲⱲᴒᴠᴡͼⱫᴅ᷄᷉Ⱡ᷊᷇ͼᴤԜᴠͼᴤᴒꞌꞌͼᴡꜝꞌᴒᴟԜᴡᴒᴑͼ꞉ꜜͼᴡⱳ꞉ᴠͼᴠᴡᴢᴑᴦͼᴤ꞉ᴡⱳͼꜜꜝͼ
ᴒᴣ꞉ᴑᴒꜜᴐᴒͼꜝⱱͼᴑꜝᴠᴒ᷄ꞌ꞉ꜛ꞉ᴡ꞉ꜜⱲͼᴡꜝᴥ꞉ᴐ꞉ᴡᴦͼԜᴡͼᴑꜝᴠᴒᴠͼᴢꜞͼᴡꜝͼ᷾᷇᷇ͼꜛⱲ᷅ͼ
ⱨͼᴡꜝᴡԜꞌͼꜝⱱͼ᷊ͼꜝᴢᴡͼꜝⱱͼⱠ᷉ͼꜞꜝᴠᴡ᷄ᴑꜝᴠᴒͼᴠԜꜛꜞꞌᴒᴠͼӿ᷊᷊᷅ӼԐԓͼꜝԝᴡԜ꞉ꜜᴒᴑͼⱱᴟꜝꜛͼ᷉ͼꜝᴢᴡͼꜝⱱͼ᷊᷉ͼᴠᴢԝ꞊ᴒᴐᴡᴠͼӿ˲᷅ⅎӼԐԓͼᴤᴒᴟᴒͼ
ᴐꜝꜜⱱ꞉ᴟꜛᴒᴑͼᴡꜝͼԝᴒͼԜꜜᴡ꞉᷄ᴑᴟᴢⱲͼԜꜜᴡ꞉ԝꜝᴑᴦ᷄ꜞꜝᴠ꞉ᴡ꞉ᴣᴒ᷅ͼ꜠ꜝͼᴠԜꜛꜞꞌᴒᴠͼᴤᴒᴟᴒͼꜞꜝᴠ꞉ᴡ꞉ᴣᴒͼⱱꜝᴟͼꜜᴒᴢᴡᴟԜꞌ꞉ᴧ꞉ꜜⱲͼԜᴐᴡ꞉ᴣ꞉ᴡᴦ᷅
ᴁⱳᴒͼꜞⱳԜᴟꜛԜᴐꜝꞋ꞉ꜜᴒᴡ꞉ᴐͼԜꜜԜꞌᴦᴠ꞉ᴠͼⱱꜝᴟͼԜꞌꞌͼᴠᴢԝ꞊ᴒᴐᴡᴠͼ꞉ꜜͼᴡⱳᴒͼ᷊᷇ԓͼ᷈᷇᷇ԓͼ᷊᷇᷇ԓͼԜꜜᴑͼ᷾᷇᷇ͼꜛⱲͼᴑꜝᴠᴒᴠͼᴠⱳꜝᴤᴒᴑͼᴑᴟᴢⱲͼ
ꞌᴒᴣᴒꞌᴠͼ꞉ꜜͼⱶⱨⱬͼᴠᴢԝ꞊ᴒᴐᴡᴠͼᴤᴒᴟᴒͼᴑꜝᴠᴒ᷄ᴑᴒꜞᴒꜜᴑᴒꜜᴡͼԜꜜᴑͼᴒᴥⱳ꞉ԝ꞉ᴡᴒᴑͼԜͼꜞᴟꜝꞌꜝꜜⱲᴒᴑͼⱳԜꞌⱱ᷄ꞌ꞉ⱱᴒͼꜝⱱͼ
Ԝꜞꜞᴟꜝᴥ꞉ꜛԜᴡᴒꞌᴦͼ᷉ͼᴤᴒᴒꞋᴠԓͼᴡᴦꜞ꞉ᴐԜꞌͼꜝⱱͼԜͼⱳᴢꜛԜꜜͼꜛꜝꜜꜝᴐꞌꜝꜜԜꞌͼԜꜜᴡ꞉ԝꜝᴑᴦ᷅ͼⱪꜛԜᴥᴑᴟᴢⱲͼꞌᴒᴣᴒꞌᴠͼ꞉ꜜᴐᴟᴒԜᴠᴒᴑͼᴤ꞉ᴡⱳͼ
꞉ꜜᴐᴟᴒԜᴠ꞉ꜜⱲͼᴑꜝᴠᴒԓͼԜᴠͼᴒᴥꜞᴒᴐᴡᴒᴑ᷅ͼᴁⱳᴒᴠᴒͼꜞԜᴟԜꜛᴒᴡᴒᴟᴠͼԜᴟᴒͼᴐꜝꜜᴠ꞉ᴠᴡᴒᴑͼᴤ꞉ᴡⱳͼᴣԜꞌᴢᴒᴠͼꜝԝᴡԜ꞉ꜜᴒᴑͼ꞉ꜜͼⱳᴒԜꞌᴡⱳᴦͼ
ᴠᴢԝ꞊ᴒᴐᴡᴠͼ꞉ꜜͼᴠᴡᴢᴑᴦͼⱫᴅ᷄᷉Ⱡ᷊᷇᷄᷇᷈᷅
ⱨͼᴄᴒᴠᴡᴒᴟꜜͼԝꞌꜝᴡͼԜᴠᴠԜᴦͼᴠⱳꜝᴤᴒᴑͼꜞᴟᴒ᷄ᴑꜝᴠᴒͼԝԜᴠᴒꞌ꞉ꜜᴒͼꞌᴒᴣᴒꞌᴠͼꜝⱱͼꜛᴒԜꜜͼ᷉᷄ᴐⱳԜ꞉ꜜͼⱳ꞉Ⱳⱳ᷄ꜛꜝꞌᴒᴐᴢꞌԜᴟ᷄ᴤᴒ꞉Ⱳⱳᴡͼ
Ꞌ꞉ꜜ꞉ꜜꜝⱲᴒꜜͼӿⱶꜚᴄꜘԐͼ꞉ꜜͼᴢꜜԜᴐᴡ꞉ᴣԜᴡᴒᴑͼꜞꞌԜᴠꜛԜͼᴐꜝꞌꞌᴒᴐᴡᴒᴑͼⱱᴟꜝꜛͼⱶⱨⱬͼꜞԜᴡ꞉ᴒꜜᴡᴠͼᴤԜᴠͼԜꜞꜞᴟꜝᴥ꞉ꜛԜᴡᴒꞌᴦͼ
᷿᷇Ӽ᷅ͼⱨͼᴠᴡԜᴡ꞉ᴠᴡ꞉ᴐԜꞌꞌᴦͼᴠ꞉Ⱳꜜ꞉ⱱ꞉ᴐԜꜜᴡͼᴟᴒᴑᴢᴐᴡ꞉ꜝꜜͼ꞉ꜜͼ᷉᷄ᴐⱳԜ꞉ꜜͼⱶꜚᴄꜘͼꞌᴒᴣᴒꞌᴠͼᴤԜᴠͼꜝԝᴠᴒᴟᴣᴒᴑͼꜝꜜͼᴠᴡᴢᴑᴦͼᴑԜᴦᴠͼ˲ͼ
Ԝꜜᴑͼ᷉᷉ͼ꞉ꜜͼᴡⱳᴒͼ᷊᷇᷇ͼԜꜜᴑͼ᷾᷇᷇ͼꜛⱲͼᴑꜝᴠᴒͼⱲᴟꜝᴢꜞᴠͼᴐꜝꜛꜞԜᴟᴒᴑͼᴡꜝͼꜞᴟᴒ᷄ᴑꜝᴠᴒͼꞌᴒᴣᴒꞌᴠԓͼꞌᴒᴣᴒꞌᴠͼᴠ꞉ꜛ꞉ꞌԜᴟͼᴡꜝͼᴡⱳԜᴡͼ
ꜝԝᴠᴒᴟᴣᴒᴑͼ꞉ꜜͼⱳᴒԜꞌᴡⱳᴦͼᴠᴢԝ꞊ᴒᴐᴡᴠ᷅ͼᴁⱳ꞉ᴠͼꜝᴢᴡᴐꜝꜛᴒͼᴑᴒꜛꜝꜜᴠᴡᴟԜᴡᴒᴠͼᴡⱳᴒͼꜞⱳԜᴟꜛԜᴐꜝᴑᴦꜜԜꜛ꞉ᴐͼԜᴐᴡ꞉ᴣ꞉ᴡᴦͼꜝⱱͼⱫᴅ᷄
᷉Ⱡ᷊᷇ͼԜꜜᴑͼ꞉ᴡᴠͼԜԝ꞉ꞌ꞉ᴡᴦͼᴡꜝͼᴒⱱⱱᴒᴐᴡ꞉ᴣᴒꞌᴦͼꜜꜝᴟꜛԜꞌ꞉ᴧᴒͼᴡⱳᴒͼ꞉ꜜᴠᴡԜԝ꞉ꞌ꞉ᴡᴦͼꜝⱱͼⱶⱨⱬͼꜞꞌԜᴠꜛԜͼ꞉ꜜͼᴡⱳ꞉ᴠͼԜᴠᴠԜᴦ᷅ͼ
͟ᴟ꞉ꜛԜᴟᴦͼᴒⱱⱱ꞉ᴐԜᴐᴦͼԜꜜԜꞌᴦᴠᴒᴠͼᴤᴒᴟᴒͼԝԜᴠᴒᴑͼꜝꜜͼᴠᴢԝ꞊ᴒᴐᴡᴠͼ꞉ꜜͼᴡⱳᴒͼ᷊᷇᷇ͼꜛⱲԓͼ᷾᷇᷇ͼꜛⱲԓͼԜꜜᴑͼꜞꞌԜᴐᴒԝꜝͼᴑꜝᴠᴒͼ
ⱲᴟꜝᴢꜞᴠͼᴤⱳꜝͼᴟᴒꜞꜝᴟᴡᴒᴑͼⱳԜᴣ꞉ꜜⱲͼԜᴡͼꞌᴒԜᴠᴡͼ᷉ͼԜᴡᴡԜᴐꞋᴠͼ꞉ꜜͼᴡⱳᴒͼ᷊ͼꜛꜝꜜᴡⱳᴠͼꜞᴟ꞉ꜝᴟͼᴡꜝͼᴠᴡᴢᴑᴦͼᴒꜜᴡᴟᴦͼ
ӿ᷿᷇᷅᷈ԜᴡᴡԜᴐꞋᴠ᷆ᴤᴒᴒꞋԐ᷅ͼ꜡ⱱͼᴡⱳꜝᴠᴒͼᴠᴢԝ꞊ᴒᴐᴡᴠͼᴡᴟᴒԜᴡᴒᴑͼᴤ꞉ᴡⱳͼ᷊᷇᷇ͼꜝᴟͼ᷾᷇᷇ͼꜛⱲͼⱫᴅ᷄᷉Ⱡ᷊᷇ԓͼ᷿᷈ͼꜝⱱͼ᷈⅍ᴠᴢԝ꞊ᴒᴐᴡᴠͼ
ꜛᴒᴡͼᴡⱳᴒᴠᴒͼᴐᴟ꞉ᴡᴒᴟ꞉Ԝ᷅ͼ꜡ⱱͼᴡⱳᴒͼꜞꞌԜᴐᴒԝꜝͼᴡᴟᴒԜᴡᴒᴑͼᴠᴢԝ꞊ᴒᴐᴡᴠԓͼ᷈᷈ͼꜝⱱͼ᷊᷈ͼᴠᴢԝ꞊ᴒᴐᴡᴠͼꜛᴒᴡͼᴡⱳᴒᴠᴒͼᴐᴟ꞉ᴡᴒᴟ꞉Ԝ᷅ͼ
ᴁⱳᴒͼԝԜᴠᴒꞌ꞉ꜜᴒͼⱶⱨⱬͼԜᴡᴡԜᴐꞋͼᴟԜᴡᴒᴠͼӿԜᴡᴡԜᴐꞋᴠ᷆ᴤᴒᴒꞋԐͼᴤᴒᴟᴒͼ᷊᷇᷅ⱠͼԜᴡᴡԜᴐꞋᴠͼꜞᴒᴟͼᴤᴒᴒꞋͼ꞉ꜜͼᴡⱳᴒͼꜞꞌԜᴐᴒԝꜝͼⱲᴟꜝᴢꜞԓͼ
᷊᷊᷇᷅ͼԜᴡᴡԜᴐꞋᴠͼꜞᴒᴟͼᴤᴒᴒꞋͼ꞉ꜜͼᴡⱳᴒͼ᷊᷇᷇ͼꜛⱲͼⱲᴟꜝᴢꜞԓͼ᷿᷿᷇᷅ͼԜᴡᴡԜᴐꞋᴠͼꜞᴒᴟͼᴤᴒᴒꞋͼ꞉ꜜͼᴡⱳᴒͼ᷾᷇᷇ͼꜛⱲͼⱲᴟꜝᴢꜞͼԜꜜᴑͼ᷇᷅᷾Ⱡͼ
ԜᴡᴡԜᴐꞋᴠͼꜞᴒᴟͼᴤᴒᴒꞋͼ꞉ꜜͼᴡⱳᴒͼ᷊᷇᷇ͼԜꜜᴑͼ᷾᷇᷇ͼꜛⱲͼᴐꜝꜛԝ꞉ꜜᴒᴑͼⱲᴟꜝᴢꜞ᷅ͼⱫᴢᴟ꞉ꜜⱲͼᴡⱳᴒͼꜞᴟᴒ᷄ᴠꜞᴒᴐ꞉ⱱ꞉ᴒᴑԓͼꜞᴟ꞉ꜛԜᴟᴦͼ
ᴒⱱⱱ꞉ᴐԜᴐᴦͼ꞉ꜜᴡᴒᴟᴣԜꞌͼꜝⱱͼ⅍ͼᴤᴒᴒꞋᴠͼӿⱱᴟꜝꜛͼᴑԜᴦᴠͼ˲ͼᴡꜝͼ᷿᷇Ɫͼᴐꜝᴟᴟᴒᴠꜞꜝꜜᴑ꞉ꜜⱲͼᴡꜝͼԜͼꜞᴒᴟ꞉ꜝᴑͼꜝⱱͼꜜꜝᴡԜԝꞌᴒͼᴑᴟᴢⱲͼ
ᴒᴥꜞꜝᴠᴢᴟᴒԐԓͼᴡⱳᴒͼⱶⱨⱬͼԜᴡᴡԜᴐꞋͼᴟԜᴡᴒԓͼԜᴑ꞊ᴢᴠᴡᴒᴑͼⱱꜝᴟͼԝԜᴠᴒꞌ꞉ꜜᴒͼԜᴡᴡԜᴐꞋͼᴟԜᴡᴒԓͼᴤԜᴠͼ᷇ͼ꞉ꜜͼᴡⱳᴒͼ᷊᷇᷇ꜛⱲͼⱲᴟꜝᴢꜞͼԜꜜᴑͼ
᷿᷇᷅᷇᷾ͼԜᴡᴡԜᴐꞋᴠͼꜞᴒᴟͼᴤᴒᴒꞋͼ꞉ꜜͼᴡⱳᴒͼ᷾᷇᷇ͼꜛⱲͼⱲᴟꜝᴢꜞԓͼᴐꜝꜛꜞԜᴟᴒᴑͼᴡꜝͼ᷊᷇᷅ⅎͼԜᴡᴡԜᴐꞋᴠͼꜞᴒᴟͼᴤᴒᴒꞋͼ꞉ꜜͼᴡⱳᴒͼꜞꞌԜᴐᴒԝꜝͼ
Ⱳᴟꜝᴢꜞ᷅ͼᴁⱳ꞉ᴠͼᴟᴒᴠᴢꞌᴡᴒᴑͼ꞉ꜜͼԜͼ᷈᷇᷇Ӽͼᴟᴒᴑᴢᴐᴡ꞉ꜝꜜͼᴣᴠͼꜞꞌԜᴐᴒԝꜝͼⱱꜝᴟͼᴡⱳᴒͼ᷊᷇᷇ͼꜛⱲͼⱫᴅ᷄᷉Ⱡ᷊᷇ͼⱲᴟꜝᴢꜞͼӿP Ᵽͼ᷇᷅᷇᷇᷇᷈Ԑͼ
ԜꜜᴑͼԜꜜͼ˲˲Ӽͼᴟᴒᴑᴢᴐᴡ꞉ꜝꜜͼᴣᴠͼꜞꞌԜᴐᴒԝꜝͼⱱꜝᴟͼ᷾᷇᷇ͼꜛⱲͼⱫᴅ᷄᷉Ⱡ᷊᷇ͼӿP Ɽͼ᷿᷇᷅᷇᷇Ԑ᷅ͼⱫᴢᴟ꞉ꜜⱲͼᴡⱳ꞉ᴠͼꜞᴟ꞉ꜛԜᴟᴦͼᴒⱱⱱ꞉ᴐԜᴐᴦͼ
꞉ꜜᴡᴒᴟᴣԜꞌԓͼ᷈᷇᷇Ӽͼꜝⱱͼᴠᴢԝ꞊ᴒᴐᴡᴠͼ꞉ꜜͼᴡⱳᴒͼ᷊᷇᷇ͼꜛⱲͼⱲᴟꜝᴢꜞͼӿP Ɽͼ᷇᷅᷇᷉⅍ԐͼԜꜜᴑͼ˲᷉Ӽͼꜝⱱͼᴠᴢԝ꞊ᴒᴐᴡᴠͼ꞉ꜜͼᴡⱳᴒͼ᷾᷇᷇ͼꜛⱲͼ
ⱲᴟꜝᴢꜞͼӿP Ɽͼ᷊᷇᷅᷇ԐͼᴤᴒᴟᴒͼԜᴡᴡԜᴐꞋ᷄ⱱᴟᴒᴒͼᴐꜝꜛꜞԜᴟᴒᴑͼᴤ꞉ᴡⱳͼ᷉ⅎӼͼꜝⱱͼᴠᴢԝ꞊ᴒᴐᴡᴠͼ꞉ꜜͼᴡⱳᴒͼꜞꞌԜᴐᴒԝꜝͼⱲᴟꜝᴢꜞ᷅
ᴁⱳᴒͼᴑԜᴡԜͼⱱᴟꜝꜛͼᴡⱳ꞉ᴠͼᴠᴡᴢᴑᴦͼᴑᴒꜛꜝꜜᴠᴡᴟԜᴡᴒͼꜞᴟꜝꜝⱱͼꜝⱱͼᴐꜝꜜᴐᴒꜞᴡͼꜝⱱͼᴡⱳᴒͼԜԝ꞉ꞌ꞉ᴡᴦͼꜝⱱͼⱫᴅ᷄᷉Ⱡ᷊᷇ͼᴡꜝͼꜞᴟᴒᴣᴒꜜᴡͼԜᴐᴢᴡᴒͼ
ԜᴡᴡԜᴐꞋᴠͼꜝⱱͼⱶⱨⱬ᷅ͼⱨͼᴠᴡԜᴡ꞉ᴠᴡ꞉ᴐԜꞌꞌᴦͼᴠ꞉Ⱳꜜ꞉ⱱ꞉ᴐԜꜜᴡͼⱱ꞉ꜜᴑ꞉ꜜⱲͼꜝⱱͼⱶⱨⱬͼԜᴡᴡԜᴐꞋͼꜞᴟᴒᴣᴒꜜᴡ꞉ꜝꜜͼԝᴦͼⱫᴅ᷄᷉Ⱡ᷊᷇ͼᴤԜᴠͼ

Ⱬᴅ᷄᷉Ⱡ᷊᷇
ⱪꞌ꞉ꜜ꞉ᴐԜꞌͼᴁᴟ꞉Ԝꞌͼ͟ᴟꜝᴡꜝᴐꜝꞌⱡͼⱫᴅ᷄᷉Ⱡ᷊᷊᷇᷄᷇
ⱨꜛᴒꜜᴑꜛᴒꜜᴡͼ᷊᷅᷇ͼⱴ꞉ꜜԜꞌⱡͼ᷇ⱠͼꜗԜꜜᴢԜᴟᴦ᷉᷇᷈ⅎ
ⱪꜝꜜⱱ꞉ᴑᴒꜜᴡ꞉Ԝꞌ
͟ԜⱲᴒͼ᷊⅍
ⱫᴦԜᴥͼⱪꜝᴟꜞ᷅
ꜝԝᴠᴒᴟᴣᴒᴑ᷅ͼⱫᴅ᷄᷉Ⱡ᷊᷇ͼᴤԜᴠͼᴤᴒꞌꞌͼᴡꜝꞌᴒᴟԜᴡᴒᴑͼ꞉ꜜͼⱶⱨⱬͼᴠᴢԝ꞊ᴒᴐᴡᴠͼᴢꜞͼᴡꜝͼ᷾᷇᷇ͼꜛⱲ᷅ͼⱫᴟᴢⱲͼᴒᴥꜞꜝᴠᴢᴟᴒͼԜꜞꜞᴒԜᴟᴠͼᴡꜝͼ
ԝᴒͼᴑꜝᴠᴒ᷄ꜞᴟꜝꜞꜝᴟᴡ꞉ꜝꜜԜꞌͼԜꜜᴑͼᴐꜝꜜᴠ꞉ᴠᴡᴒꜜᴡͼᴤ꞉ᴡⱳͼᴡⱳᴒͼᴟᴒᴠᴢꞌᴡᴠͼꜝԝᴡԜ꞉ꜜᴒᴑͼ꞉ꜜͼⱳᴒԜꞌᴡⱳᴦͼᴠᴢԝ꞊ᴒᴐᴡᴠͼ꞉ꜜͼᴠᴡᴢᴑᴦͼⱫᴅ᷄
᷉Ⱡ᷊᷇᷄᷇᷈᷅ͼ͟ⱳԜᴟꜛԜᴐꜝᴑᴦꜜԜꜛ꞉ᴐͼᴒⱱⱱᴒᴐᴡͼԜᴠᴠԜᴦᴠͼꜞᴟꜝᴣ꞉ᴑᴒͼᴒᴣ꞉ᴑᴒꜜᴐᴒͼᴡⱳԜᴡͼⱫᴅ᷄᷉Ⱡ᷊᷇ͼⱳԜᴠͼԜͼᴑ꞉ᴟᴒᴐᴡͼᴒⱱⱱᴒᴐᴡͼꜝꜜͼ
ꜞꞌԜᴠꜛԜͼꞋԜꞌꞌ꞉Ꞌᴟᴒ꞉ꜜͼԜᴐᴡ꞉ᴣ꞉ᴡᴦͼ꞉ꜜͼꜞԜᴡ꞉ᴒꜜᴡͼꜞꞌԜᴠꜛԜ᷅
ⱴꜝᴟͼԜᴑᴑ꞉ᴡ꞉ꜝꜜԜꞌͼᴑᴒᴡԜ꞉ꞌͼᴟᴒⱲԜᴟᴑ꞉ꜜⱲͼᴡⱳᴒͼꜛᴢꞌᴡ꞉ꜞꞌᴒͼᴑꜝᴠᴒԓͼᴐꞌ꞉ꜜ꞉ᴐԜꞌͼᴠᴡᴢᴑᴦͼ꞉ꜜͼⱶⱨⱬͼᴠᴢԝ꞊ᴒᴐᴡᴠԓͼꜞꞌᴒԜᴠᴒͼᴟᴒⱱᴒᴟͼᴡꜝͼ
ᴡⱳᴒͼⱫᴅ᷄᷉Ⱡ᷊᷇ͼⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟᶳᴠͼⱩᴟꜝᴐⱳᴢᴟᴒ᷅

Ⱬᴅ᷄᷉Ⱡ᷊᷇
ⱪꞌ꞉ꜜ꞉ᴐԜꞌͼᴁᴟ꞉Ԝꞌͼ͟ᴟꜝᴡꜝᴐꜝꞌⱡͼⱫᴅ᷄᷉Ⱡ᷊᷊᷇᷄᷇
ⱨꜛᴒꜜᴑꜛᴒꜜᴡͼ᷊᷅᷇ͼⱴ꞉ꜜԜꞌⱡͼ᷇ⱠͼꜗԜꜜᴢԜᴟᴦ᷉᷇᷈ⅎ
ⱪꜝꜜⱱ꞉ᴑᴒꜜᴡ꞉Ԝꞌ
͟ԜⱲᴒͼ᷊ⅎ
ⱫᴦԜᴥͼⱪꜝᴟꜞ᷅
2
STUDY OBJECTIVES
2.1
Primary Objective
ᴁꜝͼᴒᴣԜꞌᴢԜᴡᴒͼᴡⱳᴒͼᴒⱱⱱ꞉ᴐԜᴐᴦͼꜝⱱͼⱫᴅ᷄᷉Ⱡ᷊᷇ͼ꞉ꜜͼꜞᴟᴒᴣᴒꜜᴡ꞉ꜜⱲͼⱶⱨⱬͼԜᴡᴡԜᴐꞋᴠ᷅
2.2
Secondary Objective
ᴁꜝͼᴒᴣԜꞌᴢԜᴡᴒͼᴡⱳᴒͼᴠԜⱱᴒᴡᴦͼꜝⱱͼᴟᴒꜞᴒԜᴡᴒᴑͼᴠᴢԝᴐᴢᴡԜꜜᴒꜝᴢᴠͼԜᴑꜛ꞉ꜜ꞉ᴠᴡᴟԜᴡ꞉ꜝꜜᴠͼꜝⱱͼⱫᴅ᷄᷉Ⱡ᷊᷇᷅
2.3
Tertiary Objectives
ᶄ
ᴁꜝͼᴒᴣԜꞌᴢԜᴡᴒͼᴡⱳᴒͼꜞⱳԜᴟꜛԜᴐꜝᴑᴦꜜԜꜛ꞉ᴐͼӿ͟ⱫԐͼᴒⱱⱱᴒᴐᴡᴠͼꜝⱱͼᴐⱳᴟꜝꜜ꞉ᴐԜꞌꞌᴦͼԜᴑꜛ꞉ꜜ꞉ᴠᴡᴒᴟᴒᴑͼⱫᴅ᷄᷉Ⱡ᷊᷇
ᶄ
ᴁꜝͼԜᴠᴠᴒᴠᴠͼᴡⱳᴒͼ꞉ꜛꜛᴢꜜꜝⱲᴒꜜ꞉ᴐ꞉ᴡᴦͼꜝⱱͼᴐⱳᴟꜝꜜ꞉ᴐԜꞌꞌᴦͼԜᴑꜛ꞉ꜜ꞉ᴠᴡᴒᴟᴒᴑͼⱫᴅ᷄᷉Ⱡ᷊᷇
ᶄ
ᴁꜝͼᴒᴣԜꞌᴢԜᴡᴒͼᴡⱳᴒͼꜞⱳԜᴟꜛԜᴐꜝꞋ꞉ꜜᴒᴡ꞉ᴐᴠͼӿ͟ꜘԐͼꜝⱱͼᴐⱳᴟꜝꜜ꞉ᴐԜꞌꞌᴦͼԜᴑꜛ꞉ꜜ꞉ᴠᴡᴒᴟᴒᴑͼⱫᴅ᷄᷉Ⱡ᷊᷇
ᶄ
ᴁꜝͼᴒᴣԜꞌᴢԜᴡᴒͼᴡⱳᴒͼᴒⱱⱱᴒᴐᴡͼꜝⱱͼⱫᴅ᷄᷉Ⱡ᷊᷇ͼꜝꜜͼⱳᴒԜꞌᴡⱳ᷄ᴟᴒꞌԜᴡᴒᴑͼꜟᴢԜꞌ꞉ᴡᴦͼꜝⱱͼꞌ꞉ⱱᴒͼӿϷꜝꜙԐͼ

Ⱬᴅ᷄᷉Ⱡ᷊᷇
ⱪꞌ꞉ꜜ꞉ᴐԜꞌͼᴁᴟ꞉Ԝꞌͼ͟ᴟꜝᴡꜝᴐꜝꞌⱡͼⱫᴅ᷄᷉Ⱡ᷊᷊᷇᷄᷇
ⱨꜛᴒꜜᴑꜛᴒꜜᴡͼ᷊᷅᷇ͼⱴ꞉ꜜԜꞌⱡͼ᷇ⱠͼꜗԜꜜᴢԜᴟᴦ᷉᷇᷈ⅎ
ⱪꜝꜜⱱ꞉ᴑᴒꜜᴡ꞉Ԝꞌ
͟ԜⱲᴒͼ᷊˲
ⱫᴦԜᴥͼⱪꜝᴟꜞ᷅
3
INVESTIGATIONAL PLAN
3.1
Overall Study Design and Plan
3.1.1
Overview
ᴁⱳ꞉ᴠͼᴠᴡᴢᴑᴦͼ꞉ᴠͼԜͼꜞⱳԜᴠᴒͼ᷊ԓͼꜛᴢꞌᴡ꞉ᴐᴒꜜᴡᴒᴟԓͼᴟԜꜜᴑꜝꜛ꞉ᴧᴒᴑԓͼᴑꜝᴢԝꞌᴒ᷄ԝꞌ꞉ꜜᴑԓͼꜞꞌԜᴐᴒԝꜝ᷄ᴐꜝꜜᴡᴟꜝꞌꞌᴒᴑͼᴡᴟ꞉Ԝꞌͼᴡꜝͼ
ᴒᴣԜꞌᴢԜᴡᴒͼᴡⱳᴒͼᴒⱱⱱ꞉ᴐԜᴐᴦͼԜꜜᴑͼᴠԜⱱᴒᴡᴦͼꜝⱱͼⱫᴅ᷄᷉Ⱡ᷊᷇ͼ꞉ꜜͼꜞᴟᴒᴣᴒꜜᴡ꞉ꜜⱲͼԜᴐᴢᴡᴒͼԜᴡᴡԜᴐꞋᴠͼ꞉ꜜͼꜞԜᴡ꞉ᴒꜜᴡᴠͼᴤ꞉ᴡⱳͼᴁᴦꜞᴒⱷͼ
Ԝꜜᴑͼᴁᴦꜞᴒͼⱷⱷͼⱶⱨⱬ᷅ͼᴁⱳ꞉ᴠͼᴑꜝᴢԝꞌᴒ᷄ԝꞌ꞉ꜜᴑͼᴠᴡᴢᴑᴦͼ꞉ᴠͼꜞꞌԜꜜꜜᴒᴑͼᴡꜝͼԝᴒͼⱱꜝꞌꞌꜝᴤᴒᴑͼԝᴦͼԜꜜͼꜝꜞᴒꜜ᷄ꞌԜԝᴒꞌͼᴒᴥᴡᴒꜜᴠ꞉ꜝꜜͼ
ӿ꜡ꜙⱬԐͼᴡⱳԜᴡͼ꞉ᴠͼᴑᴒᴠᴐᴟ꞉ԝᴒᴑͼ꞉ꜜͼԜͼᴠᴒꜞԜᴟԜᴡᴒͼꜞᴟꜝᴡꜝᴐꜝꞌͼӿⱫᴅ᷄᷉Ⱡ᷊᷇᷄᷇᷾Ԑ᷅
ᴀᴢԝ꞊ᴒᴐᴡᴠͼԜⱲᴒᴑͼ᷈᷉ͼԜꜜᴑͼꜝᴣᴒᴟͼᴤ꞉ᴡⱳͼԜͼᴑꜝᴐᴢꜛᴒꜜᴡᴒᴑͼᴑ꞉ԜⱲꜜꜝᴠ꞉ᴠͼꜝⱱͼᴁᴦꜞᴒͼⱷͼꜝᴟͼᴁᴦꜞᴒͼⱷⱷͼⱶⱨⱬͼᴤⱳꜝͼ
ᴒᴥꜞᴒᴟ꞉ᴒꜜᴐᴒͼԜᴡͼꞌᴒԜᴠᴡͼ᷈ԜᴡᴡԜᴐꞋͼꜞᴒᴟͼ᷾ͼᴤᴒᴒꞋᴠͼᴑᴢᴟ꞉ꜜⱲͼᴡⱳᴒͼᴟᴢꜜ᷄꞉ꜜͼꜞᴒᴟ꞉ꜝᴑͼᴤ꞉ꞌꞌͼԝᴒͼᴒꞌ꞉Ⱳ꞉ԝꞌᴒ᷅ͼᴂꜞͼᴡꜝͼ᷈᷉᷇ͼ
ᴠᴢԝ꞊ᴒᴐᴡᴠͼꜛԜᴦͼԝᴒͼᴒꜜᴟꜝꞌꞌᴒᴑͼᴡꜝͼꜞᴟꜝᴣ꞉ᴑᴒͼ᷈᷇˲ͼᴡⱳԜᴡͼᴐꜝꜛꜞꞌᴒᴡᴒ᷅ͼᴀᴢԝ꞊ᴒᴐᴡᴠͼᴤ꞉ꞌꞌͼԝᴒͼᴒꜜᴟꜝꞌꞌᴒᴑͼⱱᴟꜝꜛͼᴠ꞉ᴡᴒᴠͼ꞉ꜜͼᴡⱳᴒͼ
ᴂꜜ꞉ᴡᴒᴑᴀᴡԜᴡᴒᴠԓͼⱪԜꜜԜᴑԜԓͼⱷᴡԜꞌᴦԓͼⱵᴒᴟꜛԜꜜᴦԓͼᴂꜜ꞉ᴡᴒᴑͼꜘ꞉ꜜⱲᴑꜝꜛͼԜꜜᴑͼꜗꜝᴟᴑԜꜜ᷅
3.1.1.1
Long-Term Prophylactic (LTP) Therapy Washout
ⱴꜝꞌꞌꜝᴤ꞉ꜜⱲͼ꞉ꜜⱱꜝᴟꜛᴒᴑͼᴐꜝꜜᴠᴒꜜᴡԓͼᴠᴢԝ꞊ᴒᴐᴡᴠͼᴤ꞉ꞌꞌͼᴢꜜᴑᴒᴟⱲꜝͼᴠᴐᴟᴒᴒꜜ꞉ꜜⱲͼԜᴠᴠᴒᴠᴠꜛᴒꜜᴡᴠ᷅ͼᴀᴐᴟᴒᴒꜜᴒᴑͼᴠᴢԝ꞊ᴒᴐᴡᴠͼ
ᴤⱳꜝͼԜᴟᴒͼꜝꜜͼꞌꜝꜜⱲ᷄ᴡᴒᴟꜛͼꜞᴟꜝꜞⱳᴦꞌԜᴐᴡ꞉ᴐͼᴡⱳᴒᴟԜꜞᴦͼⱱꜝᴟͼⱶⱨⱬͼԜᴟᴒͼᴟᴒꜟᴢ꞉ᴟᴒᴑͼᴡꜝͼᴢꜜᴑᴒᴟⱲꜝͼԜͼꜛ꞉ꜜ꞉ꜛᴢꜛͼ᷉ᴤᴒᴒꞋͼ
ᴤԜᴠⱳꜝᴢᴡͼꜞᴒᴟ꞉ꜝᴑͼꜞᴟ꞉ꜝᴟͼᴡꜝͼᴡⱳᴒͼᴠᴡԜᴟᴡͼꜝⱱͼᴡⱳᴒͼᴟᴢꜜ᷄꞉ꜜͼꜞᴒᴟ꞉ꜝᴑ᷅ͼᴁⱳ꞉ᴠͼꜙᴁ͟ͼᴤԜᴠⱳꜝᴢᴡͼ꞉ᴠͼꜞᴒᴟꜛ꞉ᴡᴡᴒᴑͼԜᴠͼꞌꜝꜜⱲͼԜᴠͼ
ᴡⱳᴒͼⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟͼᴑᴒᴡᴒᴟꜛ꞉ꜜᴒᴠͼᴡⱳԜᴡͼᴑꜝ꞉ꜜⱲͼᴠꜝͼᴤꜝᴢꞌᴑͼꜜꜝᴡͼꜞꞌԜᴐᴒͼᴡⱳᴒͼᴠᴢԝ꞊ᴒᴐᴡͼԜᴡͼԜꜜᴦͼᴢꜜᴑᴢᴒͼᴠԜⱱᴒᴡᴦͼᴟ꞉ᴠꞋͼԜꜜᴑͼ
ᴡⱳᴒͼᴠᴢԝ꞊ᴒᴐᴡͼ꞉ᴠͼԜᴡͼꞌᴒԜᴠᴡͼ᷈˲ͼᴦᴒԜᴟᴠͼꜝⱱͼԜⱲᴒ᷅ͼᴁⱳᴒᴠᴒͼᴐᴟ꞉ᴡᴒᴟ꞉ԜͼᴒꜜᴠᴢᴟᴒͼᴡⱳԜᴡͼꜞԜᴡ꞉ᴒꜜᴡᴠͼᴤⱳꜝͼᴠⱳꜝᴢꞌᴑͼᴟᴒꜛԜ꞉ꜜͼꜝꜜͼ
ꜙᴁ͟ͼᴑꜝͼꜜꜝᴡͼᴤԜᴠⱳꜝᴢᴡͼⱱꜝᴟͼᴡⱳ꞉ᴠͼᴠᴡᴢᴑᴦԓͼԝᴢᴡͼᴑꜝͼԜꞌꞌꜝᴤͼᴡⱳᴒͼᴒꜜᴟꜝꞌꞌꜛᴒꜜᴡͼꜝⱱͼԜꜞꜞᴟꜝꜞᴟ꞉ԜᴡᴒͼꜞԜᴡ꞉ᴒꜜᴡᴠͼᴤ꞉ᴡⱳͼ
ᴠᴒᴣᴒᴟᴒͼᴑ꞉ᴠᴒԜᴠᴒͼᴤⱳ꞉ꞌᴒͼꜛ꞉ꜜ꞉ꜛ꞉ᴧ꞉ꜜⱲͼᴡⱳᴒ꞉ᴟͼᴡ꞉ꜛᴒͼꜝⱱⱱͼꜙᴁ᷅͟ͼⱪᴢᴟᴟᴒꜜᴡͼᴡᴟᴒԜᴡꜛᴒꜜᴡͼⱲᴢ꞉ᴑᴒꞌ꞉ꜜᴒᴠͼᴟᴒᴐꜝⱲꜜ꞉ᴧᴒͼᴡᴤꜝͼ
ᴑ꞉ⱱⱱᴒᴟᴒꜜᴡͼᴠᴡԜꜜᴑԜᴟᴑͼꜝⱱͼᴐԜᴟᴒͼԜꜞꜞᴟꜝԜᴐⱳᴒᴠͼᴡꜝͼᴡᴟᴒԜᴡ꞉ꜜⱲͼⱶⱨⱬԓͼᴤⱳ꞉ᴐⱳͼ꞉ꜜᴐꞌᴢᴑᴒͼꜙᴁ͟ͼԜꜜᴑͼꜝꜜ᷄ᴑᴒꜛԜꜜᴑͼ
ᴡⱳᴒᴟԜꜞᴦͼӿⱪ꞉ᴐԜᴟᴑ꞉ͼᴒᴡͼԜꞌ᷅ԓͼ᷉᷇᷈᷉ⱢͼⱪᴟԜ꞉ⱲͼᴒᴡͼԜꞌ᷅ԓͼ᷉᷇᷈᷉ⱢͼᴇᴢᴟԜᴤͼᴒᴡͼԜꞌ᷅ԓͼ᷊᷉᷇᷈Ԑ᷅ͼᴁⱳᴟꜝᴢⱲⱳꜝᴢᴡͼᴡⱳᴒͼᴠᴡᴢᴑᴦԓͼ
ᴠᴢԝ꞊ᴒᴐᴡᴠͼᴤ꞉ꞌꞌͼԝᴒͼꜞᴒᴟꜛ꞉ᴡᴡᴒᴑͼᴡꜝͼᴡᴟᴒԜᴡͼԜᴐᴢᴡᴒͼⱶⱨⱬͼԜᴡᴡԜᴐꞋᴠͼ꞉ꜜͼԜᴐᴐꜝᴟᴑͼᴤ꞉ᴡⱳͼᴡⱳᴒͼⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟᶳᴠͼᴢᴠᴢԜꞌͼᴐԜᴟᴒͼ
ꜝⱱͼᴡⱳᴒ꞉ᴟͼꜞԜᴡ꞉ᴒꜜᴡᴠ᷅ͼᴁⱳᴢᴠԓͼᴡⱳꜝᴠᴒͼᴠᴢԝ꞊ᴒᴐᴡᴠͼᴤⱳꜝͼᴠᴡꜝꜞͼᴡⱳᴒ꞉ᴟͼꜙᴁ͟ͼᴡꜝͼᴒꜜᴡᴒᴟͼᴡⱳᴒͼᴠᴡᴢᴑᴦͼԜꜜᴑͼԜᴟᴒͼᴠᴢԝᴠᴒꜟᴢᴒꜜᴡꞌᴦͼ
ᴟԜꜜᴑꜝꜛ꞉ᴧᴒᴑͼᴡꜝͼᴡⱳᴒͼꜞꞌԜᴐᴒԝꜝͼⱲᴟꜝᴢꜞͼᴤ꞉ꞌꞌͼᴠᴡ꞉ꞌꞌͼԝᴒͼꜛԜꜜԜⱲᴒᴑͼᴤ꞉ᴡⱳͼꜜꜝͼᴟᴒᴑᴢᴐᴡ꞉ꜝꜜͼ꞉ꜜͼᴡⱳᴒ꞉ᴟͼᴠᴡԜꜜᴑԜᴟᴑͼꜝⱱͼ
ᴐԜᴟᴒ᷅ͼᴁⱳᴒͼⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟͼꜛᴢᴠᴡͼᴐꜝꜜⱱ꞉ᴟꜛͼᴡⱳԜᴡͼᴡⱳᴒͼᴠᴢԝ꞊ᴒᴐᴡͼⱳԜᴠͼᴠᴢᴐᴐᴒᴠᴠⱱᴢꞌꞌᴦͼᴐꜝꜛꜞꞌᴒᴡᴒᴑͼᴡⱳᴒͼ᷉ͼᴤᴒᴒꞋͼ
ᴤԜᴠⱳꜝᴢᴡͼꜞᴒᴟ꞉ꜝᴑͼԝᴒⱱꜝᴟᴒͼᴡⱳᴒᴦͼᴐԜꜜͼᴒꜜᴡᴒᴟͼᴡⱳᴒͼᴟᴢꜜ᷄꞉ꜜͼꜞᴒᴟ꞉ꜝᴑ᷅
3.1.1.2
Run-In Period
ᴀᴐᴟᴒᴒꜜᴒᴑͼᴠᴢԝ꞊ᴒᴐᴡᴠͼᴤⱳꜝͼԜᴟᴒͼᴒ꞉ᴡⱳᴒᴟͼꜜꜝᴡͼꜝꜜͼꞌꜝꜜⱲ᷄ᴡᴒᴟꜛͼꜞᴟꜝꜞⱳᴦꞌԜᴐᴡ꞉ᴐͼᴡⱳᴒᴟԜꜞᴦͼⱱꜝᴟͼⱶⱨⱬԓͼꜝᴟͼⱳԜᴣᴒͼ
ᴐꜝꜛꜞꞌᴒᴡᴒᴑͼᴡⱳᴒͼᴟᴒꜟᴢ꞉ᴟᴒᴑͼᴤԜᴠⱳꜝᴢᴡͼꜞᴒᴟ꞉ꜝᴑͼᴤ꞉ꞌꞌͼᴒꜜᴡᴒᴟͼԜͼᴟᴢꜜ᷄꞉ꜜͼꜞᴒᴟ꞉ꜝᴑͼꜝⱱͼ᷾ͼᴤᴒᴒꞋᴠͼᴡꜝͼᴑᴒᴡᴒᴟꜛ꞉ꜜᴒͼᴡⱳᴒͼ
ԝԜᴠᴒꞌ꞉ꜜᴒͼⱶⱨⱬͼԜᴡᴡԜᴐꞋͼᴟԜᴡᴒ᷅ͼ꜡ꜜꞌᴦͼᴠᴢԝ꞊ᴒᴐᴡᴠͼꜛᴒᴒᴡ꞉ꜜⱲͼԜͼꜛ꞉ꜜ꞉ꜛᴢꜛͼԝԜᴠᴒꞌ꞉ꜜᴒͼᴟԜᴡᴒͼꜝⱱͼԜᴡͼꞌᴒԜᴠᴡͼ᷈ͼ
ⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟ᷄ᴐꜝꜜⱱ꞉ᴟꜛᴒᴑͼⱶⱨⱬͼԜᴡᴡԜᴐꞋͼꜞᴒᴟͼ᷾ͼᴤᴒᴒꞋᴠͼᴤ꞉ꞌꞌͼԝᴒͼᴒꞌ꞉Ⱳ꞉ԝꞌᴒͼⱱꜝᴟͼᴒꜜᴟꜝꞌꞌꜛᴒꜜᴡͼԜꜜᴑͼ
ᴟԜꜜᴑꜝꜛ꞉ᴧԜᴡ꞉ꜝꜜ᷅ͼᴀᴢԝ꞊ᴒᴐᴡᴠͼᴤⱳꜝͼᴒᴥꜞᴒᴟ꞉ᴒꜜᴐᴒͼ᷊ͼꜝᴟͼꜛꜝᴟᴒͼⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟ᷄ᴐꜝꜜⱱ꞉ᴟꜛᴒᴑͼԜᴡᴡԜᴐꞋᴠͼԝᴒⱱꜝᴟᴒͼᴡⱳᴒͼᴒꜜᴑͼ
ꜝⱱͼᴡⱳᴒͼ᷾ͼᴤᴒᴒꞋᴠͼᴐԜꜜͼᴒᴥ꞉ᴡͼᴡⱳᴒͼᴟᴢꜜ᷄꞉ꜜͼꜞᴒᴟ꞉ꜝᴑͼᴒԜᴟꞌᴦͼԜꜜᴑͼꜞᴟꜝᴐᴒᴒᴑͼᴡꜝͼᴒꜜᴟꜝꞌꞌꜛᴒꜜᴡԜꜜᴑͼᴟԜꜜᴑꜝꜛ꞉ᴧԜᴡ꞉ꜝꜜ᷅ͼ
ᴀᴢԝ꞊ᴒᴐᴡᴠͼᴤ꞉ᴡⱳꜝᴢᴡͼԜᴡͼꞌᴒԜᴠᴡͼ᷈ͼⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟ᷄ᴐꜝꜜⱱ꞉ᴟꜛᴒᴑͼԜᴡᴡԜᴐꞋͼԜⱱᴡᴒᴟͼ᷾ͼᴤᴒᴒꞋᴠͼꜝⱱͼᴟᴢꜜ᷄꞉ꜜͼᴤ꞉ꞌꞌͼⱳԜᴣᴒͼᴡⱳᴒ꞉ᴟͼ
ᴟᴢꜜ᷄꞉ꜜͼꜞᴒᴟ꞉ꜝᴑͼᴒᴥᴡᴒꜜᴑᴒᴑͼⱱꜝᴟͼԜꜜꜝᴡⱳᴒᴟͼ᷾ͼᴤᴒᴒꞋᴠԓͼᴑᴢᴟ꞉ꜜⱲͼᴤⱳ꞉ᴐⱳͼᴡ꞉ꜛᴒͼᴡⱳᴒᴦͼꜜᴒᴒᴑͼᴡꜝͼⱳԜᴣᴒͼԜᴡͼꞌᴒԜᴠᴡͼ᷉ͼ
ⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟ᷄ᴐꜝꜜⱱ꞉ᴟꜛᴒᴑͼԜᴡᴡԜᴐꞋᴠͼᴡꜝͼꜞᴟꜝᴐᴒᴒᴑͼᴡꜝͼᴒꜜᴟꜝꞌꞌꜛᴒꜜᴡͼԜꜜᴑͼᴟԜꜜᴑꜝꜛ꞉ᴧԜᴡ꞉ꜝꜜ᷅ͼᴁꜝͼԝᴒͼᴒꞌ꞉Ⱳ꞉ԝꞌᴒͼⱱꜝᴟͼ
ᴒꜜᴟꜝꞌꞌꜛᴒꜜᴡԓͼᴠᴢԝ꞊ᴒᴐᴡᴠͼᴤⱳꜝͼⱳԜᴣᴒͼᴡⱳᴒ꞉ᴟͼᴟᴢꜜ᷄꞉ꜜͼᴒᴥᴡᴒꜜᴑᴒᴑͼꜛᴢᴠᴡͼᴐꜝꜛꜞꞌᴒᴡᴒͼᴡⱳᴒͼⱱᴢꞌꞌͼ˲᷄ᴤᴒᴒꞋͼᴟᴢꜜ᷄꞉ꜜͼꜞᴒᴟ꞉ꜝᴑͼ
ꜞᴟ꞉ꜝᴟͼᴡꜝͼᴒꜜᴡᴒᴟ꞉ꜜⱲͼᴡⱳᴒͼᴡᴟᴒԜᴡꜛᴒꜜᴡͼꜞᴒᴟ꞉ꜝᴑ᷅ͼᴀᴢԝ꞊ᴒᴐᴡᴠͼᴤⱳꜝͼᴑꜝͼꜜꜝᴡͼꜛᴒᴒᴡͼᴡⱳᴒͼꜛ꞉ꜜ꞉ꜛᴢꜛͼԜᴡᴡԜᴐꞋͼᴟԜᴡᴒͼᴑᴢᴟ꞉ꜜⱲͼ

Ⱬᴅ᷄᷉Ⱡ᷊᷇
ⱪꞌ꞉ꜜ꞉ᴐԜꞌͼᴁᴟ꞉Ԝꞌͼ͟ᴟꜝᴡꜝᴐꜝꞌⱡͼⱫᴅ᷄᷉Ⱡ᷊᷊᷇᷄᷇
ⱨꜛᴒꜜᴑꜛᴒꜜᴡͼ᷊᷅᷇ͼⱴ꞉ꜜԜꞌⱡͼ᷇ⱠͼꜗԜꜜᴢԜᴟᴦ᷉᷇᷈ⅎ
ⱪꜝꜜⱱ꞉ᴑᴒꜜᴡ꞉Ԝꞌ
͟ԜⱲᴒͼ᷊Ⱡ
ⱫᴦԜᴥͼⱪꜝᴟꜞ᷅
ᴟᴢꜜ᷄꞉ꜜͼꜝᴟͼԜᴟᴒͼꜝᴡⱳᴒᴟᴤ꞉ᴠᴒͼᴑᴒᴡᴒᴟꜛ꞉ꜜᴒᴑͼᴡꜝͼԝᴒͼ꞉ꜜᴒꞌ꞉Ⱳ꞉ԝꞌᴒͼᴑᴢᴒͼᴡꜝͼᴠᴐᴟᴒᴒꜜ꞉ꜜⱲͼԜᴠᴠᴒᴠᴠꜛᴒꜜᴡᴠͼᴤ꞉ꞌꞌͼԝᴒͼ
ᴐꜝꜜᴠ꞉ᴑᴒᴟᴒᴑͼԜͼᴠᴐᴟᴒᴒꜜͼⱱԜ꞉ꞌ᷅ͼᴀᴢԝ꞊ᴒᴐᴡᴠͼᴤⱳꜝͼᴠᴐᴟᴒᴒꜜͼⱱԜ꞉ꞌͼᴤ꞉ꞌꞌͼꜜꜝᴡͼԝᴒͼԜꞌꞌꜝᴤᴒᴑͼᴡꜝͼᴟᴒᴠᴐᴟᴒᴒꜜͼ꞉ꜜᴡꜝͼᴡⱳᴒͼᴠᴡᴢᴑᴦ᷅ͼ
3.1.1.3
Treatment Period
ⱨⱱᴡᴒᴟͼᴣᴒᴟ꞉ⱱ꞉ᴐԜᴡ꞉ꜝꜜͼꜝⱱͼᴒꞌ꞉Ⱳ꞉ԝ꞉ꞌ꞉ᴡᴦԓͼᴠᴢԝ꞊ᴒᴐᴡᴠͼᴤ꞉ꞌꞌͼԝᴒͼᴟԜꜜᴑꜝꜛ꞉ᴧᴒᴑͼ᷉ⱡ᷈ͼᴡꜝͼᴟᴒᴐᴒ꞉ᴣᴒͼᴟᴒꜞᴒԜᴡᴒᴑͼᴠᴢԝᴐᴢᴡԜꜜᴒꜝᴢᴠͼ
ӿᴀⱪԐͼԜᴑꜛ꞉ꜜ꞉ᴠᴡᴟԜᴡ꞉ꜝꜜᴠͼꜝⱱͼⱫᴅ᷄᷉Ⱡ᷊᷇ͼꜝᴟͼꜞꞌԜᴐᴒԝꜝͼ꞉ꜜͼԜͼᴑꜝᴢԝꞌᴒ᷄ԝꞌ꞉ꜜᴑͼⱱԜᴠⱳ꞉ꜝꜜ᷅ͼᴀᴢԝ꞊ᴒᴐᴡᴠͼᴤⱳꜝͼԜᴟᴒͼ
ᴟԜꜜᴑꜝꜛ꞉ᴧᴒᴑͼᴡꜝͼⱫᴅ᷄᷉Ⱡ᷊᷇ͼᴤ꞉ꞌꞌͼԝᴒͼԜᴠᴠ꞉Ⱳꜜᴒᴑͼ꞉ꜜͼԜͼ᷈ⱡ᷈ⱡ᷈ͼᴟԜᴡ꞉ꜝͼᴡꜝͼꜝꜜᴒͼꜝⱱͼᴡⱳᴟᴒᴒͼᴑꜝᴠᴒͼᴟᴒⱲ꞉ꜛᴒꜜᴠⱡͼ᷊᷇᷇ͼꜛⱲͼ
ᴒᴣᴒᴟᴦͼ᷉ͼᴤᴒᴒꞋᴠԓͼ᷊᷇᷇ͼꜛⱲͼᴒᴣᴒᴟᴦͼ᷾ͼᴤᴒᴒꞋᴠͼꜝᴟͼ᷿᷈᷇ꜛⱲͼᴒᴣᴒᴟᴦͼ᷾ͼᴤᴒᴒꞋᴠ᷅ͼϸԜꜜᴑꜝꜛ꞉ᴧԜᴡ꞉ꜝꜜͼ꞉ꜜᴡꜝͼԜꞌꞌͼ
ᴡᴟᴒԜᴡꜛᴒꜜᴡͼⱲᴟꜝᴢꜞᴠͼᴤ꞉ꞌꞌͼԝᴒͼᴠᴡᴟԜᴡ꞉ⱱ꞉ᴒᴑͼԝᴦͼᴡⱳᴒͼԝԜᴠᴒꞌ꞉ꜜᴒͼԜᴡᴡԜᴐꞋͼᴟԜᴡᴒͼꜝԝᴠᴒᴟᴣᴒᴑͼᴑᴢᴟ꞉ꜜⱲͼᴡⱳᴒͼᴟᴢꜜ᷄꞉ꜜͼꜞᴒᴟ꞉ꜝᴑͼ
꞉ꜜᴡꜝͼᴡⱳᴒͼⱱꜝꞌꞌꜝᴤ꞉ꜜⱲͼⱲᴟꜝᴢꜞᴠⱡͼ᷈ᴡꜝⱣ᷉ԜᴡᴡԜᴐꞋᴠͼꜞᴒᴟͼ᷾ͼᴤᴒᴒꞋᴠԓͼ᷉ͼᴡꜝͼⱣͼ᷊ͼԜᴡᴡԜᴐꞋᴠͼꜞᴒᴟͼ᷾ͼᴤᴒᴒꞋᴠԓͼԜꜜᴑͼᶒͼ᷊ͼ
ԜᴡᴡԜᴐꞋᴠͼꜞᴒᴟͼ᷾ͼᴤᴒᴒꞋᴠ᷅
ⱬԜᴐⱳͼᴠᴢԝ꞊ᴒᴐᴡͼᴤ꞉ꞌꞌͼᴢꜜᴑᴒᴟⱲꜝͼԜͼᴡᴟᴒԜᴡꜛᴒꜜᴡͼꜞᴒᴟ꞉ꜝᴑͼᴐꜝꜜᴠ꞉ᴠᴡ꞉ꜜⱲͼꜝⱱͼ᷊᷈ͼᴑꜝᴠᴒᴠͼꜝⱱͼԝꞌ꞉ꜜᴑᴒᴑͼⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡ꞉ꜝꜜԜꞌͼ
ꜚᴒᴑ꞉ᴐ꞉ꜜԜꞌͼ͟ᴟꜝᴑᴢᴐᴡͼӿⱷꜚ͟ԐԓͼⱱꜝᴟͼԜͼꜞᴒᴟ꞉ꜝᴑͼꜝⱱͼ᷉⅍ͼᴤᴒᴒꞋᴠͼⱱᴟꜝꜛͼᴡⱳᴒͼᴑԜᴡᴒͼꜝⱱͼⱱ꞉ᴟᴠᴡͼᴑꜝᴠᴒͼꜝꜜͼⱫԜᴦͼ᷇ͼᴡⱳᴟꜝᴢⱲⱳͼ
ᴡᴤꜝͼᴤᴒᴒꞋᴠͼԜⱱᴡᴒᴟͼᴡⱳᴒͼⱱ꞉ꜜԜꞌͼᴑꜝᴠᴒ᷅ͼᴀᴢԝ꞊ᴒᴐᴡᴠͼᴟԜꜜᴑꜝꜛ꞉ᴧᴒᴑͼᴡꜝͼꜝꜜᴒͼꜝⱱͼᴡⱳᴒͼ᷾ͼᴡᴟᴒԜᴡꜛᴒꜜᴡͼԜᴟꜛᴠͼᴤ꞉ꞌꞌͼᴒ꞉ᴡⱳᴒᴟͼ
ᴟᴒᴐᴒ꞉ᴣᴒͼԜͼⱫᴅ᷄᷉Ⱡ᷊᷇ͼꜝᴟͼꜞꞌԜᴐᴒԝꜝͼᴑꜝᴠᴒͼԜᴐᴐꜝᴟᴑ꞉ꜜⱲͼᴡꜝͼᴡⱳᴒͼᴑꜝᴠ꞉ꜜⱲͼᴠᴐⱳᴒᴑᴢꞌᴒͼ꞉ꜜͼᴁԜԝꞌᴒ᷉᷅ͼ
Table 2.
Treatment Period Dosing Schedule
Treatment Period
Treatment Arms: DX-2930 or Placebo
Dose 
Number
Dose Day/Week
300 mg
every 2 
weeks
300 mg
every 4 
weeks
150 mg
every 4 
weeks
Placebo
᷈
ⱫԜᴦͼ᷇᷆ᴄᴒᴒꞋͼ᷇
Ⱬᴅ᷄᷉Ⱡ᷊᷇
Ⱬᴅ᷄᷉Ⱡ᷊᷇
Ⱬᴅ᷄᷉Ⱡ᷊᷇
͟ꞌԜᴐᴒԝꜝ
᷉
ⱫԜᴦͼ᷈᷾᷆ᴄᴒᴒꞋͼ᷉
Ⱬᴅ᷄᷉Ⱡ᷊᷇
͟ꞌԜᴐᴒԝꜝ
͟ꞌԜᴐᴒԝꜝ
͟ꞌԜᴐᴒԝꜝ
᷊
ⱫԜᴦͼ᷉˲᷆ᴄᴒᴒꞋͼ᷾
Ⱬᴅ᷄᷉Ⱡ᷊᷇
Ⱬᴅ᷄᷉Ⱡ᷊᷇
Ⱬᴅ᷄᷉Ⱡ᷊᷇
͟ꞌԜᴐᴒԝꜝ
᷾
ⱫԜᴦͼ᷾᷉᷆ᴄᴒᴒꞋͼ⅍
Ⱬᴅ᷄᷉Ⱡ᷊᷇
͟ꞌԜᴐᴒԝꜝ
͟ꞌԜᴐᴒԝꜝ
͟ꞌԜᴐᴒԝꜝ
᷿
ⱫԜᴦͼ᷿⅍᷆ᴄᴒᴒꞋͼ˲
Ⱬᴅ᷄᷉Ⱡ᷊᷇
Ⱬᴅ᷄᷉Ⱡ᷊᷇
Ⱬᴅ᷄᷉Ⱡ᷊᷇
͟ꞌԜᴐᴒԝꜝ
⅍
ⱫԜᴦͼⅎ᷇᷆ᴄᴒᴒꞋͼ᷈᷇
Ⱬᴅ᷄᷉Ⱡ᷊᷇
͟ꞌԜᴐᴒԝꜝ
͟ꞌԜᴐᴒԝꜝ
͟ꞌԜᴐᴒԝꜝ
ⅎ
ⱫԜᴦͼ˲᷾᷆ᴄᴒᴒꞋͼ᷈᷉
Ⱬᴅ᷄᷉Ⱡ᷊᷇
Ⱬᴅ᷄᷉Ⱡ᷊᷇
Ⱬᴅ᷄᷉Ⱡ᷊᷇
͟ꞌԜᴐᴒԝꜝ
˲
ⱫԜᴦͼⱠ˲᷆ᴄᴒᴒꞋͼ᷈᷾
Ⱬᴅ᷄᷉Ⱡ᷊᷇
͟ꞌԜᴐᴒԝꜝ
͟ꞌԜᴐᴒԝꜝ
͟ꞌԜᴐᴒԝꜝ
Ⱡ
ⱫԜᴦͼ᷈᷈᷉᷆ᴄᴒᴒꞋͼ᷈⅍
Ⱬᴅ᷄᷉Ⱡ᷊᷇
Ⱬᴅ᷄᷉Ⱡ᷊᷇
Ⱬᴅ᷄᷉Ⱡ᷊᷇
͟ꞌԜᴐᴒԝꜝ
᷈᷇
ⱫԜᴦͼ᷈᷉⅍᷆ᴄᴒᴒꞋͼ᷈˲
Ⱬᴅ᷄᷉Ⱡ᷊᷇
͟ꞌԜᴐᴒԝꜝ
͟ꞌԜᴐᴒԝꜝ
͟ꞌԜᴐᴒԝꜝ
᷈᷈
ⱫԜᴦͼ᷈᷾᷇᷆ᴄᴒᴒꞋͼ᷉᷇
Ⱬᴅ᷄᷉Ⱡ᷊᷇
Ⱬᴅ᷄᷉Ⱡ᷊᷇
Ⱬᴅ᷄᷉Ⱡ᷊᷇
͟ꞌԜᴐᴒԝꜝ
᷈᷉
ⱫԜᴦͼ᷿᷈᷾᷆ᴄᴒᴒꞋͼ᷉᷉
Ⱬᴅ᷄᷉Ⱡ᷊᷇
͟ꞌԜᴐᴒԝꜝ
͟ꞌԜᴐᴒԝꜝ
͟ꞌԜᴐᴒԝꜝ
᷊᷈
ⱫԜᴦͼ᷈⅍˲᷆ᴄᴒᴒꞋͼ᷉᷾
Ⱬᴅ᷄᷉Ⱡ᷊᷇
Ⱬᴅ᷄᷉Ⱡ᷊᷇
Ⱬᴅ᷄᷉Ⱡ᷊᷇
͟ꞌԜᴐᴒԝꜝ
᷄᷄
ⱫԜᴦͼ᷈˲᷉᷆ᴄᴒᴒꞋͼ᷉⅍
꜠ꜝͼⱫꜝᴠᴒ
꜠ꜝͼⱫꜝᴠᴒ
꜠ꜝͼⱫꜝᴠᴒ
꜠ꜝͼⱫꜝᴠᴒ
3.1.1.4
Open-Label Extension (OLE)
ᴀᴢԝ꞊ᴒᴐᴡᴠͼᴤⱳꜝͼᴐꜝꜛꜞꞌᴒᴡᴒͼᴡⱳᴒͼᴡᴟᴒԜᴡꜛᴒꜜᴡͼꜞᴒᴟ꞉ꜝᴑͼᴤ꞉ꞌꞌͼԝᴒͼꜝⱱⱱᴒᴟᴒᴑͼᴡⱳᴒͼꜝꜞᴡ꞉ꜝꜜͼꜝⱱͼᴒꜜᴟꜝꞌꞌ꞉ꜜⱲͼ꞉ꜜͼԜꜜͼꜝꜞᴒꜜ᷄
ꞌԜԝᴒꞌͼᴒᴥᴡᴒꜜᴠ꞉ꜝꜜͼӿ꜡ꜙⱬԐͼᴠᴡᴢᴑᴦͼᴡⱳԜᴡͼᴤ꞉ꞌꞌͼԝᴒͼᴑᴒᴠᴐᴟ꞉ԝᴒᴑͼ꞉ꜜͼԜͼᴠᴒꜞԜᴟԜᴡᴒͼꜞᴟꜝᴡꜝᴐꜝꞌͼӿⱫᴅ᷄᷉Ⱡ᷊᷇᷄᷇᷾Ԑ᷅ͼ

Ⱬᴅ᷄᷉Ⱡ᷊᷇
ⱪꞌ꞉ꜜ꞉ᴐԜꞌͼᴁᴟ꞉Ԝꞌͼ͟ᴟꜝᴡꜝᴐꜝꞌⱡͼⱫᴅ᷄᷉Ⱡ᷊᷊᷇᷄᷇
ⱨꜛᴒꜜᴑꜛᴒꜜᴡͼ᷊᷅᷇ͼⱴ꞉ꜜԜꞌⱡͼ᷇ⱠͼꜗԜꜜᴢԜᴟᴦ᷉᷇᷈ⅎ
ⱪꜝꜜⱱ꞉ᴑᴒꜜᴡ꞉Ԝꞌ
͟ԜⱲᴒͼ᷾᷇
ⱫᴦԜᴥͼⱪꜝᴟꜞ᷅
ⱴ꞉Ⱳᴢᴟᴒ᷈ᴠⱳꜝᴤᴠͼԜͼᴠᴐⱳᴒꜛԜᴡ꞉ᴐͼꜝⱱͼᴡⱳᴒͼᴠᴡᴢᴑᴦͼᴑᴒᴠ꞉Ⱳꜜ᷅
Figure 1.
Overview of the Study Design
3.1.1.5
Follow-Up Period
ᴀᴢԝ꞊ᴒᴐᴡᴠͼᴤⱳꜝͼᴑꜝͼꜜꜝᴡͼꜞԜᴟᴡ꞉ᴐ꞉ꜞԜᴡᴒͼ꞉ꜜͼᴡⱳᴒͼ꜡ꜙⱬͼᴤ꞉ꞌꞌͼᴢꜜᴑᴒᴟⱲꜝͼᴠԜⱱᴒᴡᴦͼԜꜜᴑͼԜᴑᴑ꞉ᴡ꞉ꜝꜜԜꞌͼᴒᴣԜꞌᴢԜᴡ꞉ꜝꜜᴠͼӿ꞉᷅ᴒ᷅ԓͼ
͟ꜘͼԜꜜᴑͼ͟ⱫԐͼᴑᴢᴟ꞉ꜜⱲͼԜꜜͼ˲ͼᴤᴒᴒꞋͼⱱꜝꞌꞌꜝᴤ᷄ᴢꜞͼꜞᴒᴟ꞉ꜝᴑ᷅ᴀᴢԝ꞊ᴒᴐᴡᴠͼӿꜝᴟͼᴐԜᴟᴒⱲ꞉ᴣᴒᴟᴠԐͼᴤ꞉ꞌꞌͼԝᴒͼ꞉ꜜᴠᴡᴟᴢᴐᴡᴒᴑͼᴡꜝͼ
꞉ꜜⱱꜝᴟꜛͼᴡⱳᴒͼᴠ꞉ᴡᴒͼꜝⱱͼԜꜜᴦͼⱶⱨⱬͼԜᴡᴡԜᴐꞋͼᴡⱳᴒᴦͼᴒᴥꜞᴒᴟ꞉ᴒꜜᴐᴒͼⱱꜝᴟͼᴢꜞͼᴡꜝͼ᷊᷇ͼᴑԜᴦᴠͼԜⱱᴡᴒᴟͼᴡⱳᴒͼⱱ꞉ꜜԜꞌͼⱱꜝꞌꞌꜝᴤ᷄ᴢꜞͼ
ᴣ꞉ᴠ꞉ᴡ᷅
3.1.2
Safety Oversight and Stopping Rules
3.1.2.1
Interim Analysis and Data Safety Monitoring Board (DSMB)
꜠ꜝͼ꞉ꜜᴡᴒᴟ꞉ꜛͼԜꜜԜꞌᴦᴠ꞉ᴠͼ꞉ᴠͼꜞꞌԜꜜꜜᴒᴑͼⱱꜝᴟͼᴡⱳ꞉ᴠͼᴠᴡᴢᴑᴦ᷅ͼⱫᴢᴟ꞉ꜜⱲͼᴡⱳᴒͼᴠᴡᴢᴑᴦԓͼꜞԜᴡ꞉ᴒꜜᴡͼᴠԜⱱᴒᴡᴦͼᴤ꞉ꞌꞌͼԝᴒͼꜛꜝꜜ꞉ᴡꜝᴟᴒᴑͼ
ꜝꜜͼԜͼᴐꜝꜜᴡ꞉ꜜᴢꜝᴢᴠͼԝԜᴠ꞉ᴠͼԝᴦͼᴡⱳᴒͼꜚᴒᴑ꞉ᴐԜꞌͼꜚꜝꜜ꞉ᴡꜝᴟͼᴢꜜᴡ꞉ꞌͼᴡⱳᴒͼꞌԜᴠᴡͼꜞԜᴡ꞉ᴒꜜᴡͼᴐꜝꜛꜞꞌᴒᴡᴒᴠͼⱳ꞉ᴠͼꜝᴟͼⱳᴒᴟͼꞌԜᴠᴡͼ
ᴠᴐⱳᴒᴑᴢꞌᴒᴑͼᴠᴡᴢᴑᴦͼԜᴠᴠᴒᴠᴠꜛᴒꜜᴡ᷅ͼ
ⱨꜜͼ꞉ꜜᴑᴒꜞᴒꜜᴑᴒꜜᴡͼᴑԜᴡԜͼᴠԜⱱᴒᴡᴦͼꜛꜝꜜ꞉ᴡꜝᴟ꞉ꜜⱲͼԝꜝԜᴟᴑͼӿⱫᴀꜚⱩԐͼᴤ꞉ꞌꞌͼԜꞌᴠꜝͼԝᴒͼᴒᴠᴡԜԝꞌ꞉ᴠⱳᴒᴑͼᴡꜝͼꜞᴟꜝᴣ꞉ᴑᴒͼԜꜜͼ
ꜝꜜⱲꜝ꞉ꜜⱲԓͼ꞉ꜜᴑᴒꜞᴒꜜᴑᴒꜜᴡͼᴟᴒᴣ꞉ᴒᴤͼԜꜜᴑͼԜᴠᴠᴒᴠᴠꜛᴒꜜᴡͼꜝⱱͼᴡⱳᴒͼᴠԜⱱᴒᴡᴦͼᴑԜᴡԜԓͼԜꜜᴑͼᴡꜝͼᴠԜⱱᴒⱲᴢԜᴟᴑͼᴡⱳᴒͼ꞉ꜜᴡᴒᴟᴒᴠᴡᴠͼԜꜜᴑͼ
ᴠԜⱱᴒᴡᴦͼꜝⱱͼᴡⱳᴒͼꜞԜᴟᴡ꞉ᴐ꞉ꜞԜᴡ꞉ꜜⱲͼꜞԜᴡ꞉ᴒꜜᴡᴠͼ꞉ꜜͼᴡⱳᴒͼᴠᴡᴢᴑᴦͼӿᴠᴒᴒͼᴀᴒᴐᴡ꞉ꜝꜜ᷈᷇᷅ⅎⱱꜝᴟͼԜͼᴑᴒᴠᴐᴟ꞉ꜞᴡ꞉ꜝꜜͼꜝⱱͼᴡⱳᴒͼⱫᴀꜚⱩͼ
Ԝꜜᴑͼ꞉ᴡᴠͼᴟꜝꞌᴒԐ᷅ͼᴁⱳᴒͼꜝꜜⱲꜝ꞉ꜜⱲͼᴟᴒᴣ꞉ᴒᴤͼꜝⱱͼᴀⱨⱬᴠͼԜꜜᴑͼꜝᴡⱳᴒᴟͼᴟᴒᴠꜞꜝꜜᴠ꞉ԝ꞉ꞌ꞉ᴡ꞉ᴒᴠͼꜝⱱͼᴡⱳᴒͼⱫᴀꜚⱩͼԜᴟᴒͼᴑᴒᴠᴐᴟ꞉ԝᴒᴑͼ
꞉ꜜͼᴡⱳᴒͼⱫᴀꜚⱩͼⱪⱳԜᴟᴡᴒᴟ᷅ͼ
3.1.2.2
Individual Stopping Rules
Ⱬꜝᴠ꞉ꜜⱲͼⱱꜝᴟͼԜꜜᴦͼ꞉ꜜᴑ꞉ᴣ꞉ᴑᴢԜꞌͼᴠᴢԝ꞊ᴒᴐᴡͼᴤ꞉ꞌꞌͼԝᴒͼᴑ꞉ᴠᴐꜝꜜᴡ꞉ꜜᴢᴒᴑͼ꞉ⱱͼᴡⱳᴒͼᴠᴢԝ꞊ᴒᴐᴡͼᴒᴥꜞᴒᴟ꞉ᴒꜜᴐᴒᴠͼԜͼ
Ⱬᴅ᷄᷉Ⱡ᷊᷇᷄ᴟᴒꞌԜᴡᴒᴑͼᴀⱨⱬͼӿꜝᴟͼԜͼⱫᴅ᷄᷉Ⱡ᷊᷇᷄ᴟᴒꞌԜᴡᴒᴑԓͼᴐꞌ꞉ꜜ꞉ᴐԜꞌꞌᴦͼᴠ꞉Ⱳꜜ꞉ⱱ꞉ᴐԜꜜᴡͼꜜꜝꜜ᷄ᴠᴒᴟ꞉ꜝᴢᴠͼⱨⱬԐͼᴡⱳԜᴡԓͼ꞉ꜜͼᴡⱳᴒͼ
Ԝᴠᴠᴒᴠᴠꜛᴒꜜᴡͼꜝⱱͼᴡⱳᴒͼⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟԓͼᴤԜᴟᴟԜꜜᴡᴠͼᴑ꞉ᴠᴐꜝꜜᴡ꞉ꜜᴢԜᴡ꞉ꜝꜜͼⱱᴟꜝꜛͼⱱᴢᴟᴡⱳᴒᴟͼᴑꜝᴠ꞉ꜜⱲͼⱱꜝᴟͼᴡⱳԜᴡͼᴠᴢԝ꞊ᴒᴐᴡᶳᴠͼ
ᴤᴒꞌꞌ᷄ԝᴒ꞉ꜜⱲ᷅ͼᴁⱳᴒͼⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟͼⱳԜᴠͼᴡⱳᴒͼԜԝ꞉ꞌ꞉ᴡᴦͼᴡꜝͼᴐꜝꜜᴡԜᴐᴡͼԜꜜᴑͼᴐꜝꜜᴠᴢꞌᴡͼᴤ꞉ᴡⱳͼᴡⱳᴒͼꜚᴒᴑ꞉ᴐԜꞌͼꜚꜝꜜ꞉ᴡꜝᴟͼꜝꜜͼ

Ⱬᴅ᷄᷉Ⱡ᷊᷇
ⱪꞌ꞉ꜜ꞉ᴐԜꞌͼᴁᴟ꞉Ԝꞌͼ͟ᴟꜝᴡꜝᴐꜝꞌⱡͼⱫᴅ᷄᷉Ⱡ᷊᷊᷇᷄᷇
ⱨꜛᴒꜜᴑꜛᴒꜜᴡͼ᷊᷅᷇ͼⱴ꞉ꜜԜꞌⱡͼ᷇ⱠͼꜗԜꜜᴢԜᴟᴦ᷉᷇᷈ⅎ
ⱪꜝꜜⱱ꞉ᴑᴒꜜᴡ꞉Ԝꞌ
͟ԜⱲᴒͼ᷾᷈
ⱫᴦԜᴥͼⱪꜝᴟꜞ᷅
ᴠᴢᴐⱳͼꜛԜᴡᴡᴒᴟᴠ᷅ͼᴀᴢԝ꞊ᴒᴐᴡᴠͼᴤ꞉ꞌꞌͼᴐꜝꜜᴡ꞉ꜜᴢᴒͼᴡꜝͼԝᴒͼⱱꜝꞌꞌꜝᴤᴒᴑͼⱱꜝᴟͼᴡⱳᴒͼᴑᴢᴟԜᴡ꞉ꜝꜜͼꜝⱱͼᴡⱳᴒͼ᷉⅍ͼᴤᴒᴒꞋͼᴡᴟᴒԜᴡꜛᴒꜜᴡͼ
ꜞᴒᴟ꞉ꜝᴑԓͼᴢꜜꞌᴒᴠᴠͼᴡⱳᴒᴦͼᴟᴒꜟᴢᴒᴠᴡͼᴡꜝͼԝᴒͼᴑ꞉ᴠᴐꜝꜜᴡ꞉ꜜᴢᴒᴑͼⱱᴟꜝꜛͼᴡⱳᴒͼᴠᴡᴢᴑᴦ᷅ͼᴀᴢԝ꞊ᴒᴐᴡᴠͼᴤⱳꜝͼԜᴟᴒͼᴑ꞉ᴠᴐꜝꜜᴡ꞉ꜜᴢᴒᴑͼ
ⱱᴟꜝꜛͼⱱᴢᴟᴡⱳᴒᴟͼᴑꜝᴠ꞉ꜜⱲͼᴤ꞉ꞌꞌͼꜜꜝᴡͼԝᴒͼᴒꞌ꞉Ⱳ꞉ԝꞌᴒͼᴡꜝͼꜞԜᴟᴡ꞉ᴐ꞉ꜞԜᴡᴒͼ꞉ꜜͼᴡⱳᴒͼ꜡ꜙⱬ᷅
3.1.3
Follow-Up for Subjects Meeting Stopping Criteria
ᴀᴢԝ꞊ᴒᴐᴡᴠͼᴡⱳԜᴡͼᴑᴒᴣᴒꞌꜝꜞͼᴒ꞉ᴡⱳᴒᴟͼԜꜜͼᴀⱨⱬͼꜝᴟͼꜝᴡⱳᴒᴟͼᴡꜝᴥ꞉ᴐ꞉ᴡᴦͼᴐꜝꜜᴠ꞉ᴑᴒᴟᴒᴑͼᴐꞌ꞉ꜜ꞉ᴐԜꞌꞌᴦͼᴟᴒꞌᴒᴣԜꜜᴡͼ
ӿⱨⱬԓ ꞌԜԝꜝᴟԜᴡꜝᴟᴦԓͼꜞⱳᴦᴠ꞉ᴐԜꞌͼᴒᴥԜꜛ꞉ꜜԜᴡ꞉ꜝꜜԓͼᴣ꞉ᴡԜꞌͼᴠ꞉ⱲꜜԓͼꜝᴟͼⱬⱪⱵͼⱱ꞉ꜜᴑ꞉ꜜⱲԐͼᴤ꞉ꞌꞌͼԝᴒͼᴐԜᴟᴒⱱᴢꞌꞌᴦͼꜛꜝꜜ꞉ᴡꜝᴟᴒᴑͼ
ᴢꜜᴡ꞉ꞌͼᴟᴒᴠꜝꞌᴢᴡ꞉ꜝꜜԓͼᴤⱳ꞉ᴐⱳͼꜛԜᴦͼ꞉ꜜᴐꞌᴢᴑᴒͼᴡⱳᴒͼⱱꜝꞌꞌꜝᴤ꞉ꜜⱲⱡ
ᶄ
ⱨᴑᴑ꞉ᴡ꞉ꜝꜜԜꞌͼᴐꞌ꞉ꜜ꞉ᴐԜꞌͼꞌԜԝꜝᴟԜᴡꜝᴟᴦͼᴡᴒᴠᴡᴠͼԜꜜᴑ᷆ꜝᴟͼꜝᴡⱳᴒᴟͼᴐꞌ꞉ꜜ꞉ᴐԜꞌͼ꞉ꜜᴣᴒᴠᴡ꞉ⱲԜᴡ꞉ꜝꜜᴠ
ᶄ
ⱨᴑᴑ꞉ᴡ꞉ꜝꜜԜꞌͼᴣ꞉ᴠ꞉ᴡᴠͼꜝᴟͼᴒᴥᴡᴒꜜᴑᴒᴑͼᴑᴢᴟԜᴡ꞉ꜝꜜͼꜝⱱͼⱱꜝꞌꞌꜝᴤ᷄ᴢꜞ
ᶄ
꜡ԝᴡԜ꞉ꜜ꞉ꜜⱲͼԜͼᴠꜞᴒᴐ꞉Ԝꞌ꞉ᴠᴡͼᴐꜝꜜᴠᴢꞌᴡԜᴡ꞉ꜝꜜ
3.2
Rationale for Pivotal Dose Selection
ᴁⱳᴒͼᴑꜝᴠᴒͼᴟԜᴡ꞉ꜝꜜԜꞌᴒͼ꞉ᴠͼԝԜᴠᴒᴑͼꜝꜜͼᴡⱳᴒͼꜞⱳԜᴟꜛԜᴐꜝᴑᴦꜜԜꜛ꞉ᴐͼԝ꞉ꜝԜᴐᴡ꞉ᴣ꞉ᴡᴦԓͼ͟ꜘԓͼᴠԜⱱᴒᴡᴦԓͼԜꜜᴑͼᴒⱱⱱ꞉ᴐԜᴐᴦͼꜝⱱͼⱫᴅ᷄
᷉Ⱡ᷊᷇ͼⱱᴟꜝꜛͼᴡⱳᴒͼ͟ⱳԜᴠᴒͼ᷈ͼᴐꞌ꞉ꜜ꞉ᴐԜꞌͼᴠᴡᴢᴑ꞉ᴒᴠͼԜꜜᴑͼꜜꜝꜜᴐꞌ꞉ꜜ꞉ᴐԜꞌͼᴠᴡᴢᴑ꞉ᴒᴠ᷅ͼᴁꜝⱲᴒᴡⱳᴒᴟԓͼᴡⱳᴒᴠᴒͼԜᴡᴡᴟ꞉ԝᴢᴡᴒᴠͼꜞᴟꜝᴣ꞉ᴑᴒͼ
ᴡⱳᴒͼᴟԜᴡ꞉ꜝꜜԜꞌᴒͼⱱꜝᴟͼᴡⱳᴒͼᴠᴒꞌᴒᴐᴡᴒᴑͼᴑꜝᴠᴒᴠͼԜꜜᴑͼᴟᴒⱲ꞉ꜛᴒꜜᴠͼᴡꜝͼԜᴐⱳ꞉ᴒᴣᴒͼᴑᴟᴢⱲͼꞌᴒᴣᴒꞌᴠͼꞌ꞉ꞋᴒꞌᴦͼᴡꜝͼꜞᴟᴒᴣᴒꜜᴡͼԜͼ
ꜛԜ꞊ꜝᴟ꞉ᴡᴦͼꜝⱱͼⱶⱨⱬͼԜᴡᴡԜᴐꞋᴠ᷅ͼⱩԜᴠᴒᴑͼꜝꜜͼᴡⱳᴒᴠᴒͼᴐꜝꜜᴠ꞉ᴑᴒᴟԜᴡ꞉ꜝꜜᴠԓͼ᷊᷇᷇ͼꜛⱲͼᴒᴣᴒᴟᴦͼ᷉ͼᴤᴒᴒꞋᴠԓͼ᷊᷇᷇ꜛⱲͼᴒᴣᴒᴟᴦͼ᷾ͼ
ᴤᴒᴒꞋᴠԓͼԜꜜᴑͼ᷿᷈᷇ͼꜛⱲͼᴒᴣᴒᴟᴦͼ᷾ͼᴤᴒᴒꞋᴠͼᴤᴒᴟᴒͼ꞉ᴑᴒꜜᴡ꞉ⱱ꞉ᴒᴑͼԜᴠͼᴡⱳᴒͼᴑꜝᴠ꞉ꜜⱲͼᴟᴒⱲ꞉ꜛᴒꜜᴠͼⱱꜝᴟͼᴒᴣԜꞌᴢԜᴡ꞉ꜝꜜ᷅
ⱷꜜͼᴠᴡᴢᴑᴦͼⱫᴅ᷄᷉Ⱡ᷊᷇᷄᷇᷉ԓͼᴡᴤꜝͼⱫᴅ᷄᷉Ⱡ᷊᷇ͼᴑꜝᴠᴒᴠͼꜝⱱͼ᷊᷇᷇ͼꜛⱲͼꜝᴟͼⱲᴟᴒԜᴡᴒᴟͼԜᴑꜛ꞉ꜜ꞉ᴠᴡᴒᴟᴒᴑͼ᷉ͼᴤᴒᴒꞋᴠͼԜꜞԜᴟᴡͼ
ᴟᴒᴠᴢꞌᴡᴒᴑͼ꞉ꜜͼԜͼꜜꜝᴟꜛԜꞌ꞉ᴧԜᴡ꞉ꜝꜜͼꜝⱱͼꜞꞌԜᴠꜛԜͼ᷉᷄ᴐⱳԜ꞉ꜜͼⱶꜚᴄꜘͼꞌᴒᴣᴒꞌᴠͼԜꜜᴑͼԜͼꜛԜᴥ꞉ꜛԜꞌͼⱠ᷈Ӽͼᴟᴒᴑᴢᴐᴡ꞉ꜝꜜͼ꞉ꜜͼ
ⱶⱨⱬͼԜᴡᴡԜᴐꞋᴠͼӿⱫᴅ᷄᷉Ⱡ᷊᷇ͼⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟᴠͼⱩᴟꜝᴐⱳᴢᴟᴒԐ᷅ͼᴀᴡᴒԜᴑᴦ᷄ᴠᴡԜᴡᴒͼᴡᴟꜝᴢⱲⱳͼᴐꜝꜜᴐᴒꜜᴡᴟԜᴡ꞉ꜝꜜᴠͼⱱꜝꞌꞌꜝᴤ꞉ꜜⱲͼ
Ⱬᴅ᷄᷉Ⱡ᷊᷇ͼԜᴑꜛ꞉ꜜ꞉ᴠᴡᴟԜᴡ꞉ꜝꜜͼᴒᴣᴒᴟᴦͼ᷉ͼᴤᴒᴒꞋᴠͼᴤꜝᴢꞌᴑͼԝᴒͼԜꜞꜞᴟꜝᴥ꞉ꜛԜᴡᴒꞌᴦͼ᷉ⅎԓ᷇᷇᷇ͼꜜⱲ᷆ꜛꜙ᷅ͼᴁⱳᴒͼꜛԜᴥ꞉ꜛᴢꜛͼ
ꜞꞌԜᴠꜛԜͼᴐꜝꜜᴐᴒꜜᴡᴟԜᴡ꞉ꜝꜜͼӿⱪꜛԜᴥԐͼꜝԝᴡԜ꞉ꜜᴒᴑͼⱱꜝꞌꞌꜝᴤ꞉ꜜⱲͼᴒᴐԜꞌꞌԜꜜᴡ꞉ᴑᴒͼԜᴑꜛ꞉ꜜ꞉ᴠᴡᴟԜᴡ꞉ꜝꜜͼᴡꜝͼᴡᴟᴒԜᴡͼԜꜜͼԜᴐᴢᴡᴒͼԜᴡᴡԜᴐꞋͼ
꞉ᴠͼᴠ꞉ꜛ꞉ꞌԜᴟͼᴡꜝͼᴡⱳ꞉ᴠͼᴡᴟꜝᴢⱲⱳͼᴐꜝꜜᴐᴒꜜᴡᴟԜᴡ꞉ꜝꜜͼꜝⱱͼⱫᴅ᷄᷉Ⱡ᷊᷇᷅ͼ
ⱷᴡͼ꞉ᴠͼꜞꜝᴠᴠ꞉ԝꞌᴒͼᴡⱳԜᴡͼꞌꜝᴤᴒᴟͼᴑᴟᴢⱲͼꞌᴒᴣᴒꞌᴠͼᴤꜝᴢꞌᴑͼꜞᴟᴒᴣᴒꜜᴡͼԜᴡᴡԜᴐꞋᴠͼⱱꜝꞌꞌꜝᴤ꞉ꜜⱲͼꜞᴟꜝꜞⱳᴦꞌԜᴐᴡ꞉ᴐͼᴡᴟᴒԜᴡꜛᴒꜜᴡͼᴡⱳԜꜜͼ
ᴡⱳꜝᴠᴒͼᴟᴒꜟᴢ꞉ᴟᴒᴑͼⱱꜝᴟͼԜᴐᴢᴡᴒͼԜᴡᴡԜᴐꞋͼᴡᴟᴒԜᴡꜛᴒꜜᴡԓͼᴠ꞉ꜜᴐᴒͼᴠᴦᴠᴡᴒꜛ꞉ᴐͼᴑᴟᴢⱲͼᴒᴥꜞꜝᴠᴢᴟᴒͼᴐꜝᴢꞌᴑͼԜᴡᴡᴒꜜᴢԜᴡᴒͼᴐꜝꜜᴡԜᴐᴡͼ
ᴠᴦᴠᴡᴒꜛͼԜᴐᴡ꞉ᴣԜᴡ꞉ꜝꜜͼᴡⱳᴟꜝᴢⱲⱳͼᴡⱳᴒͼ꞉ꜜⱳ꞉ԝ꞉ᴡ꞉ꜝꜜͼꜝⱱͼꜞꞌԜᴠꜛԜͼꞋԜꞌꞌ꞉Ꞌᴟᴒ꞉ꜜ᷄ꜛᴒᴑ꞉ԜᴡᴒᴑͼⱴᴅⱷⱷͼԜᴐᴡ꞉ᴣԜᴡ꞉ꜝꜜ᷅ͼⱨᴠͼᴠᴢᴐⱳԓͼ
᷉ͼᴑꜝᴠ꞉ꜜⱲͼᴟᴒⱲ꞉ꜛᴒꜜᴠͼꜝⱱͼⱫᴅ᷄᷉Ⱡ᷊᷇ͼԜᴑꜛ꞉ꜜ꞉ᴠᴡᴒᴟᴒᴑͼꜛꜝꜜᴡⱳꞌᴦͼԜᴟᴒԝᴒ꞉ꜜⱲͼᴒᴣԜꞌᴢԜᴡᴒᴑ᷅ͼⱫꜝᴠᴒᴠͼꜝⱱͼ᷊᷇᷇ͼꜛⱲͼꜝᴟͼ
᷿᷈᷇ͼꜛⱲͼⱫᴅ᷄᷉Ⱡ᷊᷇ͼԜᴑꜛ꞉ꜜ꞉ᴠᴡᴒᴟᴒᴑͼᴒᴣᴒᴟᴦͼ᷾ͼᴤᴒᴒꞋᴠͼᴤꜝᴢꞌᴑͼᴟᴒᴠᴢꞌᴡͼ꞉ꜜͼԜͼᴠᴡᴒԜᴑᴦ᷄ᴠᴡԜᴡᴒͼᴡᴟꜝᴢⱲⱳͼᴐꜝꜜᴐᴒꜜᴡᴟԜᴡ꞉ꜝꜜͼ
ꜝⱱͼԜꜞꜞᴟꜝᴥ꞉ꜛԜᴡᴒꞌᴦͼⱠԓ᷿᷇᷇ͼԜꜜᴑͼ᷾ԓⅎ᷿᷇ͼꜜⱲ᷆ꜛꜙԓͼᴟᴒᴠꜞᴒᴐᴡ꞉ᴣᴒꞌᴦ᷅ͼᴁⱳᴒᴠᴒͼᴡᴟꜝᴢⱲⱳͼꞌᴒᴣᴒꞌᴠͼԝᴟԜᴐꞋᴒᴡͼᴡⱳᴒͼⱪꜛԜᴥ
ꜝԝᴠᴒᴟᴣᴒᴑͼ꞉ꜜͼᴡⱳᴒͼ᷈᷇᷇ͼꜛⱲͼᴑꜝᴠᴒͼⱲᴟꜝᴢꜞͼ꞉ꜜͼᴠᴡᴢᴑᴦͼⱫᴅ᷄᷉Ⱡ᷊᷇᷄᷇᷉ԓͼᴤⱳ꞉ᴐⱳͼᴑᴒꜛꜝꜜᴠᴡᴟԜᴡᴒᴑͼԜͼᴠꞌ꞉Ⱳⱳᴡԓͼԝᴢᴡͼꜜꜝᴡͼ
ᴠᴡԜᴡ꞉ᴠᴡ꞉ᴐԜꞌꞌᴦͼᴠ꞉Ⱳꜜ꞉ⱱ꞉ᴐԜꜜᴡԓͼᴟᴒᴑᴢᴐᴡ꞉ꜝꜜͼ꞉ꜜͼ᷉᷄ᴐⱳԜ꞉ꜜͼⱶꜚᴄꜘͼꞌᴒᴣᴒꞌᴠ᷅
ᴁⱳᴒͼ᷊ͼꜞᴟꜝꜞꜝᴠᴒᴑͼᴑꜝᴠᴒ᷄ᴟᴒⱲ꞉ꜛᴒꜜͼᴐꜝꜛԝ꞉ꜜԜᴡ꞉ꜝꜜᴠͼꜞᴟꜝᴣ꞉ᴑᴒͼԜͼ⅍᷄ⱱꜝꞌᴑͼᴟԜꜜⱲᴒͼꜝⱱͼᴠᴡᴒԜᴑᴦ᷄ᴠᴡԜᴡᴒͼᴡᴟꜝᴢⱲⱳͼ
ᴐꜝꜜᴐᴒꜜᴡᴟԜᴡ꞉ꜝꜜᴠͼԜꜜᴑͼꞌᴒᴣᴒᴟԜⱲᴒͼԝꜝᴡⱳͼᴡⱳᴒͼԝ꞉ꜝꜛԜᴟꞋᴒᴟͼԜꜜᴑᴒⱱⱱ꞉ᴐԜᴐᴦͼᴑԜᴡԜͼⱲᴒꜜᴒᴟԜᴡᴒᴑͼ꞉ꜜͼᴠᴡᴢᴑᴦͼⱫᴅ᷄᷉Ⱡ᷊᷇᷄
᷇᷉᷅ͼⱬᴣԜꞌᴢԜᴡ꞉ꜝꜜͼꜝⱱͼᴡⱳᴒͼⱫᴅ᷄᷉Ⱡ᷊᷇ͼꜞꞌԜᴠꜛԜͼᴐꜝꜜᴐᴒꜜᴡᴟԜᴡ꞉ꜝꜜᴠͼԜᴡͼᴡⱳᴒͼᴡ꞉ꜛᴒͼꜝⱱͼԜᴡᴡԜᴐꞋᴠͼᴟᴒꜞꜝᴟᴡᴒᴑͼԝᴦͼⱫᴅ᷄
᷉Ⱡ᷊᷇ͼᴡᴟᴒԜᴡᴒᴑͼᴠᴢԝ꞊ᴒᴐᴡᴠͼ꞉ꜜͼⱫᴅ᷄᷉Ⱡ᷊᷇᷄᷇᷉ͼᴠᴢⱲⱲᴒᴠᴡᴠͼᴡⱳԜᴡͼᴡⱳᴒͼ᷊ͼꜞꞌԜꜜꜜᴒᴑͼᴑꜝᴠ꞉ꜜⱲͼᴟᴒⱲ꞉ꜛᴒꜜᴠͼᴤ꞉ꞌꞌͼꜞᴟꜝᴣ꞉ᴑᴒͼԜͼ
ꜛᴒԜꜜ꞉ꜜⱲⱱᴢꞌͼᴟԜꜜⱲᴒͼꜝⱱͼᴐꞌ꞉ꜜ꞉ᴐԜꞌͼᴟᴒᴠꜞꜝꜜᴠᴒ᷅

Ⱬᴅ᷄᷉Ⱡ᷊᷇
ⱪꞌ꞉ꜜ꞉ᴐԜꞌͼᴁᴟ꞉Ԝꞌͼ͟ᴟꜝᴡꜝᴐꜝꞌⱡͼⱫᴅ᷄᷉Ⱡ᷊᷊᷇᷄᷇
ⱨꜛᴒꜜᴑꜛᴒꜜᴡͼ᷊᷅᷇ͼⱴ꞉ꜜԜꞌⱡͼ᷇ⱠͼꜗԜꜜᴢԜᴟᴦ᷉᷇᷈ⅎ
ⱪꜝꜜⱱ꞉ᴑᴒꜜᴡ꞉Ԝꞌ
͟ԜⱲᴒͼ᷾᷉
ⱫᴦԜᴥͼⱪꜝᴟꜞ᷅
3.3
Individual Subject Dosing and Follow-Up
ᴀᴢԝ꞊ᴒᴐᴡᴠͼᴤ꞉ꞌꞌͼᴟᴒᴐᴒ꞉ᴣᴒͼԜͼᴑꜝᴠᴒͼꜝⱱͼԝꞌ꞉ꜜᴑᴒᴑͼⱷꜚ͟ͼᴒᴣᴒᴟᴦͼ᷉ͼᴤᴒᴒꞋᴠͼᴑᴢᴟ꞉ꜜⱲͼᴡⱳᴒͼ᷉⅍ͼᴤᴒᴒꞋͼᴁᴟᴒԜᴡꜛᴒꜜᴡͼ͟ᴒᴟ꞉ꜝᴑͼ
ⱱꜝᴟͼԜͼᴡꜝᴡԜꞌͼꜝⱱͼ᷊᷈ͼᴑꜝᴠᴒᴠ᷅ͼᴁⱳᴒͼⱱ꞉ᴟᴠᴡͼᴑꜝᴠᴒͼꜝⱱͼⱷꜚ͟ͼᴤ꞉ꞌꞌͼԝᴒͼԜᴑꜛ꞉ꜜ꞉ᴠᴡᴒᴟᴒᴑͼꜝꜜͼⱫԜᴦͼ᷇ͼԜꜜᴑͼᴡⱳᴒͼꞌԜᴠᴡͼᴑꜝᴠᴒͼꜝⱱͼ
ⱷꜚ͟ͼᴤ꞉ꞌꞌͼԝᴒͼԜᴑꜛ꞉ꜜ꞉ᴠᴡᴒᴟᴒᴑͼꜝꜜͼⱫԜᴦͼ᷈⅍˲᷅ͼᴁⱳᴒᴟᴒͼᴤ꞉ꞌꞌͼԝᴒͼԜͼᶐ᷊ᴑԜᴦͼᴤ꞉ꜜᴑꜝᴤͼԜᴟꜝᴢꜜᴑͼᴒԜᴐⱳͼᴠᴡᴢᴑᴦͼᴣ꞉ᴠ꞉ᴡԓͼ
ᴤ꞉ᴡⱳͼԜͼꜛԜᴥ꞉ꜛᴢꜛͼꜝⱱͼ᷈ⅎͼᴑԜᴦᴠͼꜝᴟͼԜͼꜛ꞉ꜜ꞉ꜛᴢꜛͼꜝⱱͼ᷈᷈ͼᴑԜᴦᴠͼԝᴒᴡᴤᴒᴒꜜͼԜꜜᴦͼᴡᴤꜝͼᴑꜝᴠᴒᴠ᷅ͼⱨⱱᴡᴒᴟͼᴒԜᴐⱳͼᴑꜝᴠᴒԓͼ
ᴠᴢԝ꞊ᴒᴐᴡᴠͼᴤ꞉ꞌꞌͼԝᴒͼꜛꜝꜜ꞉ᴡꜝᴟᴒᴑͼԜᴡͼᴡⱳᴒͼᴠᴡᴢᴑᴦͼᴠ꞉ᴡᴒͼᴡⱳᴟꜝᴢⱲⱳͼ᷉ͼⱳꜝᴢᴟᴠͼꜞꜝᴠᴡ᷄ᴑꜝᴠᴒͼⱱꜝᴟͼᴡⱳᴒͼⱱ꞉ᴟᴠᴡͼ᷾ͼᴑꜝᴠᴒᴠͼᴤ꞉ᴡⱳͼ
ᴡⱳᴒͼԜԝ꞉ꞌ꞉ᴡᴦͼᴡꜝͼᴟᴒᴑᴢᴐᴒͼᴡⱳ꞉ᴠͼᴡ꞉ꜛᴒͼᴡꜝͼ᷈ͼⱳꜝᴢᴟͼⱱꜝᴟͼᴡⱳᴒͼᴟᴒꜛԜ꞉ꜜ꞉ꜜⱲͼᴑꜝᴠᴒᴠͼԝԜᴠᴒᴑͼꜝꜜͼᴡⱳᴒͼᴑ꞉ᴠᴐᴟᴒᴡ꞉ꜝꜜͼꜝⱱͼᴡⱳᴒͼ
ⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟͼԜꜜᴑͼᴡⱳᴒͼԜԝᴠᴒꜜᴐᴒͼꜝⱱͼᴠԜⱱᴒᴡᴦͼᴠ꞉ⱲꜜԜꞌᴠ᷅ͼⱨͼⱱꜝꞌꞌꜝᴤ᷄ᴢꜞͼᴣ꞉ᴠ꞉ᴡͼᴤ꞉ꞌꞌͼꜝᴐᴐᴢᴟͼꜝꜜͼⱫԜᴦͼ᷈˲᷉᷅ͼ
3.4
Study Duration for Individual Subjects
ⱴꜝꞌꞌꜝᴤ꞉ꜜⱲͼ꞉ꜜⱱꜝᴟꜛᴒᴑͼᴐꜝꜜᴠᴒꜜᴡԓͼᴠᴢԝ꞊ᴒᴐᴡᴠͼᴤ꞉ꞌꞌͼᴢꜜᴑᴒᴟⱲꜝͼᴠᴐᴟᴒᴒꜜ꞉ꜜⱲͼԜᴠᴠᴒᴠᴠꜛᴒꜜᴡᴠ᷅ͼᴀᴐᴟᴒᴒꜜᴒᴑͼᴠᴢԝ꞊ᴒᴐᴡᴠͼ
ᴤⱳꜝͼԜᴟᴒͼꜝꜜͼꞌꜝꜜⱲ᷄ᴡᴒᴟꜛͼꜞᴟꜝꜞⱳᴦꞌԜᴐᴡ꞉ᴐͼᴡⱳᴒᴟԜꜞᴦͼⱱꜝᴟͼⱶⱨⱬͼԜᴟᴒͼᴟᴒꜟᴢ꞉ᴟᴒᴑͼᴡꜝͼᴢꜜᴑᴒᴟⱲꜝͼԜͼꜛ꞉ꜜ꞉ꜛᴢꜛͼ᷉ᴤᴒᴒꞋͼ
ᴤԜᴠⱳ᷄ꜝᴢᴡͼꜞᴒᴟ꞉ꜝᴑͼꜞᴟ꞉ꜝᴟͼᴡꜝͼᴡⱳᴒͼᴠᴡԜᴟᴡͼꜝⱱͼᴟᴢꜜ᷄꞉ꜜ᷅ͼᴀᴢԝ꞊ᴒᴐᴡᴠͼᴤⱳꜝͼԜᴟᴒͼᴒ꞉ᴡⱳᴒᴟͼꜜꜝᴡͼꜝꜜͼꞌꜝꜜⱲ᷄ᴡᴒᴟꜛͼꜞᴟꜝꜞⱳᴦꞌԜᴐᴡ꞉ᴐͼ
ᴡⱳᴒᴟԜꜞᴦͼⱱꜝᴟͼⱶⱨⱬԓͼꜝᴟͼⱳԜᴣᴒͼᴐꜝꜛꜞꞌᴒᴡᴒᴑͼᴡⱳᴒͼᴟᴒꜟᴢ꞉ᴟᴒᴑͼᴤԜᴠⱳꜝᴢᴡͼꜞᴒᴟ꞉ꜝᴑͼᴤ꞉ꞌꞌͼᴒꜜᴡᴒᴟͼԜͼᴟᴢꜜ᷄꞉ꜜͼꜞᴒᴟ꞉ꜝᴑͼꜝⱱͼ᷾ͼ
ᴤᴒᴒꞋᴠͼᴡꜝͼᴑᴒᴡᴒᴟꜛ꞉ꜜᴒͼᴡⱳᴒͼԝԜᴠᴒꞌ꞉ꜜᴒͼⱶⱨⱬͼԜᴡᴡԜᴐꞋͼᴟԜᴡᴒ᷅ͼᴁⱳᴒͼᴟᴢꜜ᷄꞉ꜜͼꜞᴒᴟ꞉ꜝᴑͼꜛԜᴦͼꞌԜᴠᴡͼԜᴠͼꞌꜝꜜⱲͼԜᴠͼ˲ͼᴤᴒᴒꞋᴠͼ
꞉ꜜͼꜝᴟᴑᴒᴟͼᴡꜝͼꜛᴒᴒᴡͼᴡⱳᴒͼꜛ꞉ꜜ꞉ꜛᴢꜛͼԜᴡᴡԜᴐꞋͼᴟԜᴡᴒͼᴟᴒꜟᴢ꞉ᴟᴒᴑͼⱱꜝᴟͼᴒꜜᴟꜝꞌꞌꜛᴒꜜᴡ᷅ͼⱬꜜᴟꜝꞌꞌᴒᴑͼᴠᴢԝ꞊ᴒᴐᴡᴠͼᴤ꞉ꞌꞌͼᴡⱳᴒꜜͼ
ᴢꜜᴑᴒᴟⱲꜝͼԜͼ᷉⅍᷄ᴤᴒᴒꞋͼᴡᴟᴒԜᴡꜛᴒꜜᴡͼꜞᴒᴟ꞉ꜝᴑ᷅ͼᴀᴢԝ꞊ᴒᴐᴡᴠͼᴤⱳꜝͼᴑꜝͼꜜꜝᴡͼꜞԜᴟᴡ꞉ᴐ꞉ꜞԜᴡᴒͼ꞉ꜜͼᴡⱳᴒͼ꜡ꜙⱬͼᴤ꞉ꞌꞌͼԝᴒͼ
ⱱꜝꞌꞌꜝᴤᴒᴑͼⱱꜝᴟͼԜꜜͼԜᴑᴑ꞉ᴡ꞉ꜝꜜԜꞌͼ˲ͼᴤᴒᴒꞋᴠ᷅

Ⱬᴅ᷄᷉Ⱡ᷊᷇
ⱪꞌ꞉ꜜ꞉ᴐԜꞌͼᴁᴟ꞉Ԝꞌͼ͟ᴟꜝᴡꜝᴐꜝꞌⱡͼⱫᴅ᷄᷉Ⱡ᷊᷊᷇᷄᷇
ⱨꜛᴒꜜᴑꜛᴒꜜᴡͼ᷊᷅᷇ͼⱴ꞉ꜜԜꞌⱡͼ᷇ⱠͼꜗԜꜜᴢԜᴟᴦ᷉᷇᷈ⅎ
ⱪꜝꜜⱱ꞉ᴑᴒꜜᴡ꞉Ԝꞌ
͟ԜⱲᴒͼ᷊᷾
ⱫᴦԜᴥͼⱪꜝᴟꜞ᷅
4
STUDY POPULATION SELECTION
4.1
Study Population
ᴁⱳᴒͼᴠᴡᴢᴑᴦͼᴤ꞉ꞌꞌͼᴒꜜᴟꜝꞌꞌͼᴢꜞͼᴡꜝͼ᷈᷉᷇ͼᴠᴢԝ꞊ᴒᴐᴡᴠͼᴡꜝͼꜞᴟꜝᴣ꞉ᴑᴒͼ᷈᷇˲ͼᴐꜝꜛꜞꞌᴒᴡᴒᴑ᷅ͼᴀᴢԝ꞊ᴒᴐᴡᴠͼᴤ꞉ꞌꞌͼԝᴒͼ᷈᷉ᴦᴒԜᴟᴠͼꜝⱱͼ
ԜⱲᴒͼԜꜜᴑͼꜝꞌᴑᴒᴟͼᴤ꞉ᴡⱳͼԜͼᴐꜝꜜⱱ꞉ᴟꜛᴒᴑͼᴑ꞉ԜⱲꜜꜝᴠ꞉ᴠͼꜝⱱͼⱶⱨⱬͼӿᴁᴦꜞᴒͼⱷͼꜝᴟͼⱷⱷԐͼᴤⱳꜝͼᴒᴥꜞᴒᴟ꞉ᴒꜜᴐᴒͼԜᴡͼꞌᴒԜᴠᴡͼ
᷈ⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟ᷄ᴐꜝꜜⱱ꞉ᴟꜛᴒᴑͼԜᴡᴡԜᴐꞋͼꜞᴒᴟͼ᷾ͼᴤᴒᴒꞋᴠͼᴑᴢᴟ꞉ꜜⱲͼᴡⱳᴒͼᴟᴢꜜ᷄꞉ꜜͼꜞᴒᴟ꞉ꜝᴑ᷅ͼⱶⱨⱬͼᴑ꞉ԜⱲꜜꜝᴠ꞉ᴠͼᴤ꞉ꞌꞌͼԝᴒͼ
ᴐꜝꜜⱱ꞉ᴟꜛᴒᴑͼᴡⱳᴟꜝᴢⱲⱳͼᴑꜝᴐᴢꜛᴒꜜᴡᴒᴑͼᴐꞌ꞉ꜜ꞉ᴐԜꞌͼⱳ꞉ᴠᴡꜝᴟᴦͼᴐꜝꜜᴠ꞉ᴠᴡᴒꜜᴡͼᴤ꞉ᴡⱳͼⱶⱨⱬͼԜꜜᴑͼᴑ꞉ԜⱲꜜꜝᴠᴡ꞉ᴐͼᴡᴒᴠᴡ꞉ꜜⱲͼ
ᴐꜝꜜᴑᴢᴐᴡᴒᴑͼᴑᴢᴟ꞉ꜜⱲͼᴡⱳᴒͼᴠᴐᴟᴒᴒꜜ꞉ꜜⱲͼᴣ꞉ᴠ꞉ᴡ᷅ͼ
ᴁⱳᴒͼᴠᴢԝ꞊ᴒᴐᴡͼꜞꜝꜞᴢꞌԜᴡ꞉ꜝꜜͼ꞉ꜜᴐꞌᴢᴑᴒᴠͼᴠᴢԝ꞊ᴒᴐᴡᴠͼᴤⱳꜝͼԜᴟᴒͼ᷈᷉ͼᴡꜝͼ᷈ⅎͼᴦᴒԜᴟᴠͼꜝꞌᴑ᷅ͼꜙ꞉ꞋᴒͼԜᴑᴢꞌᴡᴠԓͼᴐⱳ꞉ꞌᴑᴟᴒꜜͼᴤ꞉ᴡⱳͼ
ⱶⱨⱬͼᴐԜꜜͼᴠᴢⱱⱱᴒᴟͼⱱᴟꜝꜛͼᴟᴒᴐᴢᴟᴟᴒꜜᴡͼԜꜜᴑͼᴑᴒԝ꞉ꞌ꞉ᴡԜᴡ꞉ꜜⱲͼԜᴡᴡԜᴐꞋᴠ᷅ͼᴀᴦꜛꜞᴡꜝꜛᴠͼꜛԜᴦͼꜞᴟᴒᴠᴒꜜᴡͼᴣᴒᴟᴦͼᴒԜᴟꞌᴦͼ꞉ꜜͼ
ᴐⱳ꞉ꞌᴑⱳꜝꜝᴑԓͼԜꜜᴑͼᴢꜞꜞᴒᴟͼԜ꞉ᴟᴤԜᴦͼԜꜜⱲ꞉ꜝᴒᴑᴒꜛԜͼⱳԜᴠͼԝᴒᴒꜜͼᴟᴒꜞꜝᴟᴡᴒᴑͼ꞉ꜜͼⱶⱨⱬͼꜞԜᴡ꞉ᴒꜜᴡᴠͼԜᴠͼᴦꜝᴢꜜⱲͼԜᴠͼᴡⱳᴒͼԜⱲᴒͼ
ꜝⱱͼ᷊ͼӿⱩꜝᴟꞋͼᴒᴡͼԜꞌ᷅ԓͼ᷊᷉᷇᷇Ԑ᷅ͼⱷꜜͼꜝꜜᴒͼᴐԜᴠᴒͼᴠᴒᴟ꞉ᴒᴠͼꜝⱱͼ᷾Ⱡͼꜞᴒᴑ꞉Ԝᴡᴟ꞉ᴐͼⱶⱨⱬͼꜞԜᴡ꞉ᴒꜜᴡᴠԓͼ᷊᷉ⱳԜᴑͼᴠᴢⱱⱱᴒᴟᴒᴑͼԜᴡͼꞌᴒԜᴠᴡͼ
ꜝꜜᴒͼᴒꜞ꞉ᴠꜝᴑᴒͼꜝⱱͼԜ꞉ᴟᴤԜᴦͼԜꜜⱲ꞉ꜝᴒᴑᴒꜛԜͼԝᴦͼᴡⱳᴒͼԜⱲᴒͼꜝⱱͼ᷈˲ͼӿⱴԜᴟꞋԜᴠԓͼ᷉᷇᷈᷇Ԑ᷅ͼⱨꜜͼ꞉ꜛꜞꜝᴟᴡԜꜜᴡͼᴢꜜꜛᴒᴡͼꜛᴒᴑ꞉ᴐԜꞌͼ
ꜜᴒᴒᴑͼᴒᴥ꞉ᴠᴡᴠͼԜꜛꜝꜜⱲͼᴐⱳ꞉ꞌᴑᴟᴒꜜͼᴤ꞉ᴡⱳͼⱶⱨⱬԓͼᴒᴠꜞᴒᴐ꞉ԜꞌꞌᴦͼԜᴑꜝꞌᴒᴠᴐᴒꜜᴡᴠԓͼᴠ꞉ꜜᴐᴒͼᴡⱳᴒͼᴑ꞉ᴠᴒԜᴠᴒͼᴐꜝꜛꜛꜝꜜꞌᴦͼ
ᴤꜝᴟᴠᴒꜜᴠͼԜⱱᴡᴒᴟͼꜞᴢԝᴒᴟᴡᴦͼӿⱩᴒꜜꜜᴒᴡᴡͼԜꜜᴑͼⱪᴟԜ꞉Ⱳԓͼ᷿᷉᷇᷈ⱢͼᴇᴢᴟԜᴤԓͼ᷉᷇᷇˲Ԑ᷅ͼᴁⱳᴒͼᴠᴡᴢᴑᴦͼᴤ꞉ꞌꞌͼԜ꞉ꜛͼᴡꜝͼᴒꜜᴟꜝꞌꞌͼԜᴡͼ
ꞌᴒԜᴠᴡͼ᷿ͼᴠᴢԝ꞊ᴒᴐᴡᴠͼᴤⱳꜝͼԜᴟᴒͼ᷈᷉ͼᴡꜝͼ᷈ⅎͼᴦᴒԜᴟᴠͼꜝⱱͼԜⱲᴒ᷅
4.2
Inclusion Criteria
ⱬԜᴐⱳͼᴠᴢԝ꞊ᴒᴐᴡͼꜛᴢᴠᴡͼꜛᴒᴒᴡͼᴡⱳᴒͼⱱꜝꞌꞌꜝᴤ꞉ꜜⱲͼᴐᴟ꞉ᴡᴒᴟ꞉Ԝͼᴡꜝͼԝᴒͼᴒꜜᴟꜝꞌꞌᴒᴑͼ꞉ꜜͼᴡⱳ꞉ᴠͼᴠᴡᴢᴑᴦⱡ
᷈᷅ꜚԜꞌᴒᴠͼԜꜜᴑͼⱱᴒꜛԜꞌᴒᴠͼ᷈᷉ͼᴦᴒԜᴟᴠͼꜝⱱͼԜⱲᴒͼꜝᴟͼꜝꞌᴑᴒᴟͼԜᴡͼᴡⱳᴒͼᴡ꞉ꜛᴒͼꜝⱱͼᴠᴐᴟᴒᴒꜜ꞉ꜜⱲ᷅
᷉᷅Ⱬꜝᴐᴢꜛᴒꜜᴡᴒᴑͼᴑ꞉ԜⱲꜜꜝᴠ꞉ᴠͼꜝⱱͼⱶⱨⱬͼӿᴁᴦꜞᴒͼⱷͼꜝᴟͼⱷⱷԐͼԝԜᴠᴒᴑͼᴢꜞꜝꜜͼԜꞌꞌꜝⱱͼᴡⱳᴒͼⱱꜝꞌꞌꜝᴤ꞉ꜜⱲⱡͼ
᷄
Ⱬꜝᴐᴢꜛᴒꜜᴡᴒᴑͼᴐꞌ꞉ꜜ꞉ᴐԜꞌⱳ꞉ᴠᴡꜝᴟᴦͼᴐꜝꜜᴠ꞉ᴠᴡᴒꜜᴡͼᴤ꞉ᴡⱳͼⱶⱨⱬͼӿᴠᴢԝᴐᴢᴡԜꜜᴒꜝᴢᴠͼꜝᴟͼꜛᴢᴐꜝᴠԜꞌԓͼꜜꜝꜜꜞᴟᴢᴟ꞉ᴡ꞉ᴐͼ
ᴠᴤᴒꞌꞌ꞉ꜜⱲͼᴒꜞ꞉ᴠꜝᴑᴒᴠͼᴤ꞉ᴡⱳꜝᴢᴡͼԜᴐᴐꜝꜛꜞԜꜜᴦ꞉ꜜⱲͼᴢᴟᴡ꞉ᴐԜᴟ꞉ԜԐ᷅
᷄
Ⱬ꞉ԜⱲꜜꜝᴠᴡ꞉ᴐͼᴡᴒᴠᴡ꞉ꜜⱲͼᴟᴒᴠᴢꞌᴡᴠͼꜝԝᴡԜ꞉ꜜᴒᴑͼᴑᴢᴟ꞉ꜜⱲͼᴠᴐᴟᴒᴒꜜ꞉ꜜⱲͼᴡⱳԜᴡͼᴐꜝꜜⱱ꞉ᴟꜛͼⱶⱨⱬͼᴁᴦꜞᴒͼⱷͼꜝᴟͼⱷⱷⱡͼⱪ᷈ͼ
꞉ꜜⱳ꞉ԝ꞉ᴡꜝᴟͼӿⱪ᷈᷄ⱷ꜠ⱶԐͼⱱᴢꜜᴐᴡ꞉ꜝꜜԜꞌͼꞌᴒᴣᴒꞌͼⱣͼ᷾᷇ӼͼꜝⱱͼᴡⱳᴒͼꜜꜝᴟꜛԜꞌͼꞌᴒᴣᴒꞌ᷅ͼᴀᴢԝ꞊ᴒᴐᴡᴠͼᴤ꞉ᴡⱳͼⱱᴢꜜᴐᴡ꞉ꜝꜜԜꞌͼ
ⱪ᷈᷄ⱷ꜠ⱶͼꞌᴒᴣᴒꞌͼ᷿᷾᷇᷄᷇ӼͼꜝⱱͼᴡⱳᴒͼꜜꜝᴟꜛԜꞌͼꞌᴒᴣᴒꞌͼꜛԜᴦͼԝᴒͼᴒꜜᴟꜝꞌꞌᴒᴑͼ꞉ⱱͼᴡⱳᴒᴦͼԜꞌᴠꜝͼⱳԜᴣᴒͼԜͼⱪ᷾ͼꞌᴒᴣᴒꞌͼ
ԝᴒꞌꜝᴤͼᴡⱳᴒͼꜜꜝᴟꜛԜꞌͼᴟԜꜜⱲᴒ᷅ͼᴀᴢԝ꞊ᴒᴐᴡᴠͼꜛԜᴦͼԝᴒⱲ꞉ꜜͼꜞԜᴟᴡ꞉ᴐ꞉ꜞԜᴡ꞉ꜜⱲͼ꞉ꜜͼᴡⱳᴒͼᴟᴢꜜ᷄꞉ꜜͼꜞᴒᴟ꞉ꜝᴑͼԝᴒⱱꜝᴟᴒͼ
ᴡⱳᴒᴠᴒͼᴑ꞉ԜⱲꜜꜝᴠᴡ꞉ᴐͼᴟᴒᴠᴢꞌᴡᴠͼԜᴟᴒͼԜᴣԜ꞉ꞌԜԝꞌᴒ᷅ͼᴀᴢԝ꞊ᴒᴐᴡᴠͼꜛԜᴦͼԝᴒͼᴟᴒᴡᴒᴠᴡᴒᴑͼ꞉ⱱͼᴟᴒᴠᴢꞌᴡᴠͼԜᴟᴒͼ꞉ꜜᴐꜝꜜⱲᴟᴢᴒꜜᴡͼ
ᴤ꞉ᴡⱳͼᴐꞌ꞉ꜜ꞉ᴐԜꞌͼⱳ꞉ᴠᴡꜝᴟᴦͼꜝᴟͼԝᴒꞌ꞉ᴒᴣᴒᴑͼԝᴦͼᴡⱳᴒͼⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟͼᴡꜝͼԝᴒͼᴐꜝꜜⱱꜝᴢꜜᴑᴒᴑͼԝᴦͼᴟᴒᴐᴒꜜᴡͼꜙᴁ͟ͼᴢᴠᴒ᷅
᷄
ⱨᴡͼꞌᴒԜᴠᴡͼꜝꜜᴒͼꜝⱱͼᴡⱳᴒͼⱱꜝꞌꞌꜝᴤ꞉ꜜⱲⱡͼԜⱲᴒͼԜᴡͼᴟᴒꜞꜝᴟᴡᴒᴑͼꜝꜜᴠᴒᴡͼꜝⱱͼⱱ꞉ᴟᴠᴡͼԜꜜⱲ꞉ꜝᴒᴑᴒꜛԜͼᴠᴦꜛꜞᴡꜝꜛᴠͼᶑ᷊᷇ͼ
ᴦᴒԜᴟᴠԓͼԜͼⱱԜꜛ꞉ꞌᴦͼⱳ꞉ᴠᴡꜝᴟᴦͼᴐꜝꜜᴠ꞉ᴠᴡᴒꜜᴡͼᴤ꞉ᴡⱳͼⱶⱨⱬͼᴁᴦꜞᴒͼⱷͼꜝᴟͼⱷⱷԓͼꜝᴟͼⱪ᷈ꜟͼᴤ꞉ᴡⱳ꞉ꜜͼꜜꜝᴟꜛԜꞌͼᴟԜꜜⱲᴒ᷅
᷊᷅ⱬᴥꜞᴒᴟ꞉ᴒꜜᴐ꞉ꜜⱲͼԜͼԝԜᴠᴒꞌ꞉ꜜᴒͼᴟԜᴡᴒͼꜝⱱͼԜᴡͼꞌᴒԜᴠᴡͼ᷈ͼⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟ᷄ᴐꜝꜜⱱ꞉ᴟꜛᴒᴑͼⱶⱨⱬͼԜᴡᴡԜᴐꞋͼꜞᴒᴟͼ᷾ᴤᴒᴒꞋᴠͼԜᴠͼ
ᴐꜝꜜⱱ꞉ᴟꜛᴒᴑͼᴑᴢᴟ꞉ꜜⱲͼᴡⱳᴒͼᴟᴢꜜ᷄꞉ꜜͼꜞᴒᴟ꞉ꜝᴑ᷅ͼ
᷾᷅ⱨᴑᴢꞌᴡͼᴠᴢԝ꞊ᴒᴐᴡᴠͼԜꜜᴑͼᴐԜᴟᴒⱲ꞉ᴣᴒᴟᴠͼꜝⱱͼᴠᴢԝ꞊ᴒᴐᴡᴠͼᴢꜜᴑᴒᴟͼᴡⱳᴒͼԜⱲᴒͼꜝⱱͼ᷈˲ͼԜᴟᴒͼᴤ꞉ꞌꞌ꞉ꜜⱲͼԜꜜᴑԜԝꞌᴒͼᴡꜝͼᴟᴒԜᴑԓͼ
ᴢꜜᴑᴒᴟᴠᴡԜꜜᴑԓͼԜꜜᴑͼᴠ꞉ⱲꜜͼԜꜜͼ꞉ꜜⱱꜝᴟꜛᴒᴑͼᴐꜝꜜᴠᴒꜜᴡͼⱱꜝᴟꜛ᷅ͼᴀᴢԝ꞊ᴒᴐᴡᴠͼԜⱲᴒͼ᷈᷉ͼᴡꜝͼ᷈ⅎԓͼᴤⱳꜝᴠᴒͼᴐԜᴟᴒⱲ꞉ᴣᴒᴟͼ
ꜞᴟꜝᴣ꞉ᴑᴒᴠͼ꞉ꜜⱱꜝᴟꜛᴒᴑͼᴐꜝꜜᴠᴒꜜᴡԓͼԜᴟᴒͼᴤ꞉ꞌꞌ꞉ꜜⱲͼԜꜜᴑͼԜԝꞌᴒͼᴡꜝͼᴟᴒԜᴑԓͼᴢꜜᴑᴒᴟᴠᴡԜꜜᴑͼԜꜜᴑͼᴠ꞉ⱲꜜͼԜꜜͼԜᴠᴠᴒꜜᴡͼⱱꜝᴟꜛ᷅
᷿᷅ꜚԜꞌᴒᴠͼԜꜜᴑͼⱱᴒꜛԜꞌᴒᴠͼᴤⱳꜝͼԜᴟᴒͼⱱᴒᴟᴡ꞉ꞌᴒͼԜꜜᴑͼᴠᴒᴥᴢԜꞌꞌᴦͼԜᴐᴡ꞉ᴣᴒͼꜛᴢᴠᴡͼԜᴑⱳᴒᴟᴒͼᴡꜝͼᴐꜝꜜᴡᴟԜᴐᴒꜞᴡ꞉ꜝꜜͼ
ᴟᴒꜟᴢ꞉ᴟᴒꜛᴒꜜᴡᴠͼⱱꜝᴟͼᴡⱳᴒͼᴑᴢᴟԜᴡ꞉ꜝꜜͼꜝⱱͼᴡⱳᴒͼᴠᴡᴢᴑᴦͼԜᴠͼⱱꜝꞌꞌꜝᴤᴠⱡ
᷄
ⱴᴒꜛԜꞌᴒᴠͼꜝⱱͼᴐⱳ꞉ꞌᴑԝᴒԜᴟ꞉ꜜⱲͼꜞꜝᴡᴒꜜᴡ꞉ԜꞌͼꜛᴢᴠᴡͼԜⱲᴟᴒᴒͼᴡꜝͼԝᴒͼԜԝᴠᴡ꞉ꜜᴒꜜᴡͼꜝᴟͼ꞉ᴡͼ꞉ᴠͼᴟᴒᴐꜝꜛꜛᴒꜜᴑᴒᴑͼᴡꜝͼᴢᴠᴒͼ
ⱳ꞉Ⱳⱳꞌᴦͼᴒⱱⱱᴒᴐᴡ꞉ᴣᴒͼⱱꜝᴟꜛᴠͼꜝⱱͼᴐꜝꜜᴡᴟԜᴐᴒꜞᴡ꞉ꜝꜜͼⱱᴟꜝꜛͼᴠᴐᴟᴒᴒꜜ꞉ꜜⱲͼᴡⱳᴟꜝᴢⱲⱳͼ᷊᷇ᴑԜᴦᴠͼԜⱱᴡᴒᴟͼᴡⱳᴒͼⱱ꞉ꜜԜꞌͼ
ᴠᴡᴢᴑᴦͼᴣ꞉ᴠ꞉ᴡ᷅ͼᴁⱳ꞉ᴠͼ꞉ꜜᴐꞌᴢᴑᴒᴠͼꜞᴟꜝⱲᴒᴠᴡ꞉ꜜ᷄ꜝꜜꞌᴦͼꜝᴟԜꞌͼᴐꜝꜜᴡᴟԜᴐᴒꜞᴡ꞉ᴣᴒͼԜᴠᴠꜝᴐ꞉Ԝᴡᴒᴑͼᴤ꞉ᴡⱳͼ꞉ꜜⱳ꞉ԝ꞉ᴡ꞉ꜝꜜͼꜝⱱͼ
ꜝᴣᴢꞌԜᴡ꞉ꜝꜜͼӿꜝᴟԜꞌԓͼ꞉ꜜ꞊ᴒᴐᴡԜԝꞌᴒͼꜝᴟͼ꞉ꜛꜞꞌԜꜜᴡԜԝꞌᴒԐԓͼ꞉ꜜᴡᴟԜᴢᴡᴒᴟ꞉ꜜᴒͼᴑᴒᴣ꞉ᴐᴒͼӿⱷᴂⱫԓͼԜꞌꞌͼᴡᴦꜞᴒᴠԐͼꜝᴟͼ

Ⱬᴅ᷄᷉Ⱡ᷊᷇
ⱪꞌ꞉ꜜ꞉ᴐԜꞌͼᴁᴟ꞉Ԝꞌͼ͟ᴟꜝᴡꜝᴐꜝꞌⱡͼⱫᴅ᷄᷉Ⱡ᷊᷊᷇᷄᷇
ⱨꜛᴒꜜᴑꜛᴒꜜᴡͼ᷊᷅᷇ͼⱴ꞉ꜜԜꞌⱡͼ᷇ⱠͼꜗԜꜜᴢԜᴟᴦ᷉᷇᷈ⅎ
ⱪꜝꜜⱱ꞉ᴑᴒꜜᴡ꞉Ԝꞌ
͟ԜⱲᴒͼ᷾᷾
ⱫᴦԜᴥͼⱪꜝᴟꜞ᷅
꞉ꜜᴡᴟԜᴢᴡᴒᴟ꞉ꜜᴒͼⱳꜝᴟꜛꜝꜜᴒͼᴟᴒꞌᴒԜᴠ꞉ꜜⱲͼᴠᴦᴠᴡᴒꜛᴠͼӿⱷᴂᴀԐ᷅ͼ꜠ꜝᴡᴒᴠⱡͼ᷈ԐͼⱨͼⱱᴒꜛԜꞌᴒͼᴤⱳꜝᴠᴒͼꜛԜꞌᴒͼꜞԜᴟᴡꜜᴒᴟͼ
ⱳԜᴠͼⱳԜᴑͼԜͼᴣԜᴠᴒᴐᴡꜝꜛᴦͼꜛᴢᴠᴡͼԜⱲᴟᴒᴒͼᴡꜝͼᴢᴠᴒͼꜝꜜᴒͼԜᴑᴑ꞉ᴡ꞉ꜝꜜԜꞌͼⱱꜝᴟꜛͼꜝⱱͼꜛᴒᴑ꞉ᴐԜꞌꞌᴦͼԜᴐᴐᴒꜞᴡԜԝꞌᴒͼ
ᴐꜝꜜᴡᴟԜᴐᴒꜞᴡ꞉ꜝꜜ᷅ͼ᷉ԐͼᴂᴠᴒͼꜝⱱͼԜͼꜛԜꞌᴒͼᴐꜝꜜᴑꜝꜛͼᴤ꞉ᴡⱳͼꜝᴟͼᴤ꞉ᴡⱳꜝᴢᴡͼᴠꜞᴒᴟꜛ꞉ᴐ꞉ᴑᴒͼꜝᴟͼᴐᴒᴟᴣ꞉ᴐԜꞌͼᴐԜꜞԓͼ
ᴑ꞉ԜꜞⱳᴟԜⱲꜛͼꜝᴟͼᴠꜞꜝꜜⱲᴒͼᴤ꞉ᴡⱳͼᴠꜞᴒᴟꜛ꞉ᴐ꞉ᴑᴒͼꜝᴟͼԜͼᴐꜝꜛԝ꞉ꜜԜᴡ꞉ꜝꜜͼӿᴑꜝᴢԝꞌᴒ᷄ԝԜᴟᴟ꞉ᴒᴟͼꜛᴒᴡⱳꜝᴑᴠԐͼ꞉ᴠͼꜜꜝᴡͼ
ᴐꜝꜜᴠ꞉ᴑᴒᴟᴒᴑͼⱳ꞉Ⱳⱳꞌᴦͼᴒⱱⱱᴒᴐᴡ꞉ᴣᴒ᷅ͼ
᷄
ⱴᴒꜛԜꞌᴒᴠͼꜝⱱͼꜜꜝꜜ᷄ᴐⱳ꞉ꞌᴑԝᴒԜᴟ꞉ꜜⱲͼꜞꜝᴡᴒꜜᴡ꞉Ԝꞌԓͼᴑᴒⱱ꞉ꜜᴒᴑͼԜᴠͼᴠᴢᴟⱲ꞉ᴐԜꞌꞌᴦͼᴠᴡᴒᴟ꞉ꞌᴒͼӿᴠᴡԜᴡᴢᴠͼꜞꜝᴠᴡͼ
ⱳᴦᴠᴡᴒᴟᴒᴐᴡꜝꜛᴦԓͼԝ꞉ꞌԜᴡᴒᴟԜꞌͼꜝꜝꜞⱳꜝᴟᴒᴐᴡꜝꜛᴦԓͼꜝᴟͼԝ꞉ꞌԜᴡᴒᴟԜꞌͼᴡᴢԝԜꞌͼꞌ꞉ⱲԜᴡ꞉ꜝꜜԐͼꜝᴟͼꜞꜝᴠᴡ᷄ꜛᴒꜜꜝꜞԜᴢᴠԜꞌͼⱱꜝᴟͼ
ԜᴡͼꞌᴒԜᴠᴡͼ᷈᷉ͼꜛꜝꜜᴡⱳᴠͼᴑꜝͼꜜꜝᴡͼᴟᴒꜟᴢ꞉ᴟᴒͼᴐꜝꜜᴡᴟԜᴐᴒꜞᴡ꞉ꜝꜜͼᴑᴢᴟ꞉ꜜⱲͼᴡⱳᴒͼᴠᴡᴢᴑᴦ᷅
᷄
ꜚԜꞌᴒᴠԓͼ꞉ꜜᴐꞌᴢᴑ꞉ꜜⱲͼꜛԜꞌᴒᴠͼᴤⱳꜝͼԜᴟᴒͼᴠᴢᴟⱲ꞉ᴐԜꞌꞌᴦͼᴠᴡᴒᴟ꞉ꞌᴒͼӿꜞꜝᴠᴡͼᴣԜᴠᴒᴐᴡꜝꜛᴦԐԓͼᴤ꞉ᴡⱳͼⱱᴒꜛԜꞌᴒͼꜞԜᴟᴡꜜᴒᴟᴠͼ
ꜝⱱͼᴐⱳ꞉ꞌᴑԝᴒԜᴟ꞉ꜜⱲͼꜞꜝᴡᴒꜜᴡ꞉ԜꞌͼꜛᴢᴠᴡͼԜⱲᴟᴒᴒͼᴡꜝͼԝᴒͼԜԝᴠᴡ꞉ꜜᴒꜜᴡͼꜝᴟͼᴒꞌᴠᴒͼᴢᴠᴒͼԜͼꜛᴒᴑ꞉ᴐԜꞌꞌᴦͼԜᴐᴐᴒꜞᴡԜԝꞌᴒͼ
ⱱꜝᴟꜛͼꜝⱱͼᴐꜝꜜᴡᴟԜᴐᴒꜞᴡ꞉ꜝꜜͼⱱᴟꜝꜛͼᴠᴐᴟᴒᴒꜜ꞉ꜜⱲͼᴡⱳᴟꜝᴢⱲⱳͼ⅍᷇ᴑԜᴦᴠͼԜⱱᴡᴒᴟͼᴡⱳᴒͼⱱ꞉ꜜԜꞌͼᴠᴡᴢᴑᴦͼᴣ꞉ᴠ꞉ᴡ᷅ͼ
4.3
Exclusion Criteria
ᴀᴢԝ꞊ᴒᴐᴡᴠͼᴤⱳꜝͼꜛᴒᴒᴡͼԜꜜᴦͼꜝⱱͼᴡⱳᴒͼⱱꜝꞌꞌꜝᴤ꞉ꜜⱲͼᴐᴟ꞉ᴡᴒᴟ꞉Ԝͼᴤ꞉ꞌꞌͼԝᴒͼᴒᴥᴐꞌᴢᴑᴒᴑͼⱱᴟꜝꜛͼᴡⱳᴒͼᴠᴡᴢᴑᴦⱡ
᷈᷅ⱪꜝꜜᴐꜝꜛ꞉ᴡԜꜜᴡͼᴑ꞉ԜⱲꜜꜝᴠ꞉ᴠͼꜝⱱͼԜꜜꜝᴡⱳᴒᴟͼⱱꜝᴟꜛͼꜝⱱͼᴐⱳᴟꜝꜜ꞉ᴐԓͼᴟᴒᴐᴢᴟᴟᴒꜜᴡͼԜꜜⱲ꞉ꜝᴒᴑᴒꜛԜԓͼᴠᴢᴐⱳͼԜᴠͼԜᴐꜟᴢ꞉ᴟᴒᴑͼ
ԜꜜⱲ꞉ꜝᴒᴑᴒꜛԜͼӿⱨⱨⱬԐԓͼⱶⱨⱬͼᴤ꞉ᴡⱳͼꜜꜝᴟꜛԜꞌͼⱪ᷈᷄ⱷ꜠ⱶͼӿԜꞌᴠꜝͼꞋꜜꜝᴤꜜͼԜᴠͼⱶⱨⱬͼᴁᴦꜞᴒͼⱷⱷⱷԐԓͼ꞉ᴑ꞉ꜝꜞԜᴡⱳ꞉ᴐͼ
ԜꜜⱲ꞉ꜝᴒᴑᴒꜛԜԓͼꜝᴟͼᴟᴒᴐᴢᴟᴟᴒꜜᴡͼԜꜜⱲ꞉ꜝᴒᴑᴒꜛԜͼԜᴠᴠꜝᴐ꞉Ԝᴡᴒᴑͼᴤ꞉ᴡⱳͼᴢᴟᴡ꞉ᴐԜᴟ꞉Ԝ᷅
᷉᷅͟Ԝᴟᴡ꞉ᴐ꞉ꜞԜᴡ꞉ꜝꜜͼ꞉ꜜͼԜͼꜞᴟ꞉ꜝᴟͼⱫᴅ᷄᷉Ⱡ᷊᷇ͼᴠᴡᴢᴑᴦ᷅
᷊᷅Ⱬꜝᴠ꞉ꜜⱲͼᴤ꞉ᴡⱳͼԜꜜͼ꞉ꜜᴣᴒᴠᴡ꞉ⱲԜᴡ꞉ꜝꜜԜꞌͼᴑᴟᴢⱲͼꜝᴟͼᴒᴥꜞꜝᴠᴢᴟᴒͼᴡꜝͼԜꜜͼ꞉ꜜᴣᴒᴠᴡ꞉ⱲԜᴡ꞉ꜝꜜԜꞌͼᴑᴒᴣ꞉ᴐᴒͼᴤ꞉ᴡⱳ꞉ꜜͼ᷾ᴤᴒᴒꞋᴠͼ
ꜞᴟ꞉ꜝᴟͼᴠᴐᴟᴒᴒꜜ꞉ꜜⱲ᷅
᷾᷅ⱬᴥꜞꜝᴠᴢᴟᴒͼᴡꜝͼԜꜜⱲ꞉ꜝᴡᴒꜜᴠ꞉ꜜ᷄ᴐꜝꜜᴣᴒᴟᴡ꞉ꜜⱲͼᴒꜜᴧᴦꜛᴒͼӿⱨⱪⱬԐͼ꞉ꜜⱳ꞉ԝ꞉ᴡꜝᴟᴠͼꜝᴟͼԜꜜᴦͼᴒᴠᴡᴟꜝⱲᴒꜜ᷄ᴐꜝꜜᴡԜ꞉ꜜ꞉ꜜⱲͼ
ꜛᴒᴑ꞉ᴐԜᴡ꞉ꜝꜜᴠͼᴤ꞉ᴡⱳͼᴠᴦᴠᴡᴒꜛ꞉ᴐͼԜԝᴠꜝᴟꜞᴡ꞉ꜝꜜͼӿᴠᴢᴐⱳͼԜᴠͼꜝᴟԜꞌͼᴐꜝꜜᴡᴟԜᴐᴒꜞᴡ꞉ᴣᴒᴠͼꜝᴟͼⱳꜝᴟꜛꜝꜜԜꞌͼᴟᴒꜞꞌԜᴐᴒꜛᴒꜜᴡͼ
ᴡⱳᴒᴟԜꜞᴦԐͼᴤ꞉ᴡⱳ꞉ꜜͼ᷾ͼᴤᴒᴒꞋᴠͼꜞᴟ꞉ꜝᴟͼᴡꜝͼᴠᴐᴟᴒᴒꜜ꞉ꜜⱲ᷅
᷿᷅ⱬᴥꜞꜝᴠᴢᴟᴒͼᴡꜝͼԜꜜᴑᴟꜝⱲᴒꜜᴠͼӿᴒ᷅Ⱳ᷅ͼᴠᴡԜꜜꜝᴧꜝꞌꜝꞌԓͼᴑԜꜜԜᴧꜝꞌԓͼꜝᴥԜꜜᴑᴟꜝꞌꜝꜜᴒԓͼꜛᴒᴡⱳᴦꞌᴡᴒᴠᴡꜝᴠᴡᴒᴟꜝꜜᴒԓͼ
ᴡᴒᴠᴡꜝᴠᴡᴒᴟꜝꜜᴒԐͼᴤ꞉ᴡⱳ꞉ꜜͼ᷉ͼᴤᴒᴒꞋᴠͼꜞᴟ꞉ꜝᴟͼᴡꜝͼᴒꜜᴡᴒᴟ꞉ꜜⱲͼᴡⱳᴒͼᴟᴢꜜ᷄꞉ꜜͼꜞᴒᴟ꞉ꜝᴑ᷅
⅍᷅ᴂᴠᴒͼꜝⱱͼꞌꜝꜜⱲ᷄ᴡᴒᴟꜛͼꜞᴟꜝꜞⱳᴦꞌԜᴐᴡ꞉ᴐͼᴡⱳᴒᴟԜꜞᴦͼⱱꜝᴟͼⱶⱨⱬͼӿⱪ᷈᷄ⱷ꜠ⱶԓͼԜᴡᴡᴒꜜᴢԜᴡᴒᴑͼԜꜜᴑᴟꜝⱲᴒꜜᴠԓͼꜝᴟͼԜꜜᴡ꞉᷄
ⱱ꞉ԝᴟ꞉ꜜꜝꞌᴦᴡ꞉ᴐᴠԐͼᴤ꞉ᴡⱳ꞉ꜜͼ᷉ͼᴤᴒᴒꞋᴠͼꜞᴟ꞉ꜝᴟͼᴡꜝͼᴒꜜᴡᴒᴟ꞉ꜜⱲͼᴡⱳᴒͼᴟᴢꜜ᷄꞉ꜜͼꜞᴒᴟ꞉ꜝᴑ᷅
ⅎ᷅ᴂᴠᴒͼꜝⱱͼᴠⱳꜝᴟᴡ᷄ᴡᴒᴟꜛͼꜞᴟꜝꜞⱳᴦꞌԜᴥ꞉ᴠͼⱱꜝᴟͼⱶⱨⱬͼᴤ꞉ᴡⱳ꞉ꜜͼⅎͼᴑԜᴦᴠͼꜞᴟ꞉ꜝᴟͼᴡꜝͼᴒꜜᴡᴒᴟ꞉ꜜⱲͼᴡⱳᴒͼᴟᴢꜜ᷄꞉ꜜͼꜞᴒᴟ꞉ꜝᴑ᷅ͼ
ᴀⱳꜝᴟᴡ᷄ᴡᴒᴟꜛͼꜞᴟꜝꜞⱳᴦꞌԜᴥ꞉ᴠͼ꞉ᴠͼᴑᴒⱱ꞉ꜜᴒᴑͼԜᴠͼⱪ᷈᷄ⱷ꜠ⱶԓͼԜᴡᴡᴒꜜᴢԜᴡᴒᴑͼԜꜜᴑᴟꜝⱲᴒꜜᴠԓͼꜝᴟͼԜꜜᴡ꞉᷄ⱱ꞉ԝᴟ꞉ꜜꜝꞌᴦᴡ꞉ᴐᴠͼᴢᴠᴒᴑͼ
ᴡꜝͼԜᴣꜝ꞉ᴑͼԜꜜⱲ꞉ꜝᴒᴑᴒꜛԜͼᴐꜝꜛꜞꞌ꞉ᴐԜᴡ꞉ꜝꜜᴠͼⱱᴟꜝꜛͼꜛᴒᴑ꞉ᴐԜꞌꞌᴦͼ꞉ꜜᴑ꞉ᴐԜᴡᴒᴑͼꜞᴟꜝᴐᴒᴑᴢᴟᴒᴠ᷅
˲᷅ⱨꜜᴦͼꜝⱱͼᴡⱳᴒͼⱱꜝꞌꞌꜝᴤ꞉ꜜⱲͼꞌ꞉ᴣᴒᴟͼⱱᴢꜜᴐᴡ꞉ꜝꜜͼᴡᴒᴠᴡͼԜԝꜜꜝᴟꜛԜꞌ꞉ᴡ꞉ᴒᴠⱡͼԜꞌԜꜜ꞉ꜜᴒͼԜꜛ꞉ꜜꜝᴡᴟԜꜜᴠⱱᴒᴟԜᴠᴒͼӿⱨꜙᴁԐ ⱥ᷊ᴥͼ
ᴢꜞꜞᴒᴟͼꞌ꞉ꜛ꞉ᴡͼꜝⱱͼꜜꜝᴟꜛԜꞌԓͼꜝᴟͼԜᴠꜞԜᴟᴡԜᴡᴒͼԜꜛ꞉ꜜꜝᴡᴟԜꜜᴠⱱᴒᴟԜᴠᴒͼӿⱨᴀᴁԐͼⱥͼ᷊ᴥͼᴢꜞꜞᴒᴟͼꞌ꞉ꜛ꞉ᴡͼꜝⱱͼꜜꜝᴟꜛԜꞌԓͼꜝᴟͼ
ᴡꜝᴡԜꞌͼԝ꞉ꞌ꞉ᴟᴢԝ꞉ꜜͼⱥͼ᷉ᴥͼᴢꜞꜞᴒᴟͼꞌ꞉ꜛ꞉ᴡͼꜝⱱͼꜜꜝᴟꜛԜꞌͼӿᴢꜜꞌᴒᴠᴠͼᴡⱳᴒͼԝ꞉ꞌ꞉ᴟᴢԝ꞉ꜜͼᴒꞌᴒᴣԜᴡ꞉ꜝꜜͼ꞉ᴠͼԜͼᴟᴒᴠᴢꞌᴡͼꜝⱱͼ
Ⱶ꞉ꞌԝᴒᴟᴡᶳᴠͼᴠᴦꜜᴑᴟꜝꜛᴒԐ᷅
Ⱡ᷅͟ᴟᴒⱲꜜԜꜜᴐᴦͼꜝᴟͼԝᴟᴒԜᴠᴡⱱᴒᴒᴑ꞉ꜜⱲ᷅
᷈᷇᷅ᴀᴢԝ꞊ᴒᴐᴡͼⱳԜᴠͼԜꜜᴦͼᴐꜝꜜᴑ꞉ᴡ꞉ꜝꜜͼᴡⱳԜᴡԓͼ꞉ꜜͼᴡⱳᴒͼꜝꜞ꞉ꜜ꞉ꜝꜜͼꜝⱱͼᴡⱳᴒͼⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟͼꜝᴟͼᴀꜞꜝꜜᴠꜝᴟԓͼꜛԜᴦͼ
ᴐꜝꜛꜞᴟꜝꜛ꞉ᴠᴒͼᴡⱳᴒ꞉ᴟͼᴠԜⱱᴒᴡᴦͼꜝᴟͼᴐꜝꜛꜞꞌ꞉Ԝꜜᴐᴒԓͼꜞᴟᴒᴐꞌᴢᴑᴒͼᴠᴢᴐᴐᴒᴠᴠⱱᴢꞌͼᴐꜝꜜᴑᴢᴐᴡͼꜝⱱͼᴡⱳᴒͼᴠᴡᴢᴑᴦԓͼꜝᴟͼ꞉ꜜᴡᴒᴟⱱᴒᴟᴒͼ
ᴤ꞉ᴡⱳͼ꞉ꜜᴡᴒᴟꜞᴟᴒᴡԜᴡ꞉ꜝꜜͼꜝⱱͼᴡⱳᴒͼᴟᴒᴠᴢꞌᴡᴠͼӿᴒ᷅Ⱳ᷅ԓͼⱳ꞉ᴠᴡꜝᴟᴦͼꜝⱱͼᴠᴢԝᴠᴡԜꜜᴐᴒͼԜԝᴢᴠᴒͼꜝᴟͼᴑᴒꜞᴒꜜᴑᴒꜜᴐᴒԓͼᴠ꞉Ⱳꜜ꞉ⱱ꞉ᴐԜꜜᴡͼ
ꜞᴟᴒ᷄ᴒᴥ꞉ᴠᴡ꞉ꜜⱲͼ꞉ꞌꞌꜜᴒᴠᴠͼꜝᴟͼꜝᴡⱳᴒᴟͼꜛԜ꞊ꜝᴟͼᴐꜝꜛꜝᴟԝ꞉ᴑ꞉ᴡᴦͼᴡⱳԜᴡͼᴡⱳᴒͼⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟͼᴐꜝꜜᴠ꞉ᴑᴒᴟᴠͼꜛԜᴦͼᴐꜝꜜⱱꜝᴢꜜᴑͼ
ᴡⱳᴒͼ꞉ꜜᴡᴒᴟꜞᴟᴒᴡԜᴡ꞉ꜝꜜͼꜝⱱͼᴠᴡᴢᴑᴦͼᴟᴒᴠᴢꞌᴡᴠԐ᷅

Ⱬᴅ᷄᷉Ⱡ᷊᷇
ⱪꞌ꞉ꜜ꞉ᴐԜꞌͼᴁᴟ꞉Ԝꞌͼ͟ᴟꜝᴡꜝᴐꜝꞌⱡͼⱫᴅ᷄᷉Ⱡ᷊᷊᷇᷄᷇
ⱨꜛᴒꜜᴑꜛᴒꜜᴡͼ᷊᷅᷇ͼⱴ꞉ꜜԜꞌⱡͼ᷇ⱠͼꜗԜꜜᴢԜᴟᴦ᷉᷇᷈ⅎ
ⱪꜝꜜⱱ꞉ᴑᴒꜜᴡ꞉Ԝꞌ
͟ԜⱲᴒͼ᷿᷾
ⱫᴦԜᴥͼⱪꜝᴟꜞ᷅
5
STUDY TREATMENT(S)
5.1
Description of Treatment(s)
ⱴꜝᴟͼᴑᴒᴡԜ꞉ꞌᴒᴑͼ꞉ꜜⱱꜝᴟꜛԜᴡ꞉ꜝꜜͼᴟᴒⱲԜᴟᴑ꞉ꜜⱲͼⱷꜚ͟ͼԜᴑꜛ꞉ꜜ꞉ᴠᴡᴟԜᴡ꞉ꜝꜜԓͼᴟᴒⱱᴒᴟͼᴡꜝͼᴡⱳᴒͼ͟ⱳԜᴟꜛԜᴐᴦͼꜚԜꜜᴢԜꞌ᷅
5.1.1
DX-2930
Ⱬᴅ᷄᷉Ⱡ᷊᷇ͼ꞉ᴠͼԜͼᴠᴡᴒᴟ꞉ꞌᴒԓͼꜞᴟᴒᴠᴒᴟᴣԜᴡ꞉ᴣᴒ᷄ⱱᴟᴒᴒͼᴠꜝꞌᴢᴡ꞉ꜝꜜͼⱱꜝᴟͼ꞉ꜜ꞊ᴒᴐᴡ꞉ꜝꜜԓͼꜞⱶͼ⅍᷅᷇᷅ͼᴁⱳᴒͼԜᴐᴡ꞉ᴣᴒͼ꞉ꜜⱲᴟᴒᴑ꞉ᴒꜜᴡԓͼ
Ⱬᴅ᷄᷉Ⱡ᷊᷇ԓͼ꞉ᴠͼⱱꜝᴟꜛᴢꞌԜᴡᴒᴑͼᴢᴠ꞉ꜜⱲͼᴡⱳᴒͼⱱꜝꞌꞌꜝᴤ꞉ꜜⱲͼᴐꜝꜛꜞᴒꜜᴑ꞉Ԝꞌͼᴐꜝꜛꜞꜝꜜᴒꜜᴡᴠⱡͼ᷊᷇ͼꜛꜚͼᴠꜝᴑ꞉ᴢꜛͼꜞⱳꜝᴠꜞⱳԜᴡᴒͼ
ᴑ꞉ԝԜᴠ꞉ᴐͼᴑ꞉ⱳᴦᴑᴟԜᴡᴒԓͼ᷈Ⱡ᷅⅍ͼꜛꜚͼᴐ꞉ᴡᴟ꞉ᴐͼԜᴐ꞉ᴑԓͼ᷿᷇ͼꜛꜚͼⱳ꞉ᴠᴡ꞉ᴑ꞉ꜜᴒԓͼⱠ᷇ͼꜛꜚͼᴠꜝᴑ꞉ᴢꜛͼᴐⱳꞌꜝᴟ꞉ᴑᴒԓͼ᷇᷅᷇᷈Ӽͼ
͟ꜝꞌᴦᴠꜝᴟԝԜᴡᴒ˲᷇᷅ͼⱬԜᴐⱳͼᴣ꞉ԜꞌͼᴐꜝꜜᴡԜ꞉ꜜᴠͼԜͼꜜꜝꜛ꞉ꜜԜꞌͼᴐꜝꜜᴐᴒꜜᴡᴟԜᴡ꞉ꜝꜜͼꜝⱱͼ᷿᷈᷇ͼꜛⱲͼⱫᴅ᷄᷉Ⱡ᷊᷇ͼԜᴐᴡ꞉ᴣᴒͼ
꞉ꜜⱲᴟᴒᴑ꞉ᴒꜜᴡͼ꞉ꜜͼ᷈ꜛꜙͼᴠꜝꞌᴢᴡ꞉ꜝꜜ᷅ͼᴁⱳᴒͼᴡᴒᴠᴡͼꜞᴟꜝᴑᴢᴐᴡͼᴤ꞉ꞌꞌͼԝᴒͼԜᴑꜛ꞉ꜜ꞉ᴠᴡᴒᴟᴒᴑͼԝᴦͼᴠᴢԝᴐᴢᴡԜꜜᴒꜝᴢᴠͼ꞉ꜜ꞊ᴒᴐᴡ꞉ꜝꜜͼ꞉ꜜᴡꜝͼ
ᴡⱳᴒͼᴢꜞꜞᴒᴟͼԜᴟꜛͼ꞉ꜜͼԜͼԝꞌ꞉ꜜᴑᴒᴑͼꜛԜꜜꜜᴒᴟ᷅
ⱴꜝᴟͼᴒԜᴐⱳͼ᷊᷇᷇ꜛⱲͼᴑꜝᴠᴒͼꜝⱱͼⱫᴅ᷄᷉Ⱡ᷊᷇ԓͼᴒԜᴐⱳͼᴠᴢԝ꞊ᴒᴐᴡͼᴤ꞉ꞌꞌͼᴟᴒᴐᴒ꞉ᴣᴒͼԜͼᴡꜝᴡԜꞌͼꜝⱱͼ᷉ͼꜛꜙԓͼᴑ꞉ᴣ꞉ᴑᴒᴑͼ꞉ꜜᴡꜝͼ
᷉ᴠᴒꜞԜᴟԜᴡᴒͼ᷈᷅᷇ͼꜛꜙͼᴀⱪͼ꞉ꜜ꞊ᴒᴐᴡ꞉ꜝꜜᴠͼꜝⱱͼⱫᴅ᷄᷉Ⱡ᷊᷇᷅ͼᴁⱳᴒͼ᷉ͼ꞉ꜜ꞊ᴒᴐᴡ꞉ꜝꜜᴠͼᴤ꞉ꞌꞌͼԝᴒͼⱲ꞉ᴣᴒꜜͼ꞉ꜜͼᴡⱳᴒͼᴠԜꜛᴒͼᴢꜞꜞᴒᴟͼ
Ԝᴟꜛԓͼᴤ꞉ᴡⱳͼԜᴡͼꞌᴒԜᴠᴡͼ᷉ͼᴐꜛͼᴠᴒꜞԜᴟԜᴡ꞉ꜝꜜͼԝᴒᴡᴤᴒᴒꜜͼᴒԜᴐⱳͼ꞉ꜜ꞊ᴒᴐᴡ꞉ꜝꜜͼᴠ꞉ᴡᴒ᷅
ⱴꜝᴟͼᴒԜᴐⱳͼ᷿᷈᷇ͼꜛⱲͼᴑꜝᴠᴒͼꜝⱱͼⱫᴅ᷄᷉Ⱡ᷊᷇ԓͼᴒԜᴐⱳͼᴠᴢԝ꞊ᴒᴐᴡͼᴤ꞉ꞌꞌͼᴟᴒᴐᴒ꞉ᴣᴒͼԜͼᴡꜝᴡԜꞌͼꜝⱱͼ᷉ͼꜛꜙԓͼᴑ꞉ᴣ꞉ᴑᴒᴑͼ꞉ꜜᴡꜝͼ
᷉ᴠᴒꜞԜᴟԜᴡᴒͼ᷈᷅᷇ͼꜛꜙͼᴀⱪͼ꞉ꜜ꞊ᴒᴐᴡ꞉ꜝꜜᴠԓͼᴤⱳᴒᴟᴒͼꜝꜜᴒͼ꞉ꜜ꞊ᴒᴐᴡ꞉ꜝꜜͼ꞉ᴠͼⱫᴅ᷄᷉Ⱡ᷊᷇ͼԜꜜᴑͼᴡⱳᴒͼꜝᴡⱳᴒᴟͼ꞉ᴠͼꜞꞌԜᴐᴒԝꜝ᷅ͼᴁⱳᴒͼ᷉ͼ
꞉ꜜ꞊ᴒᴐᴡ꞉ꜝꜜᴠͼᴤ꞉ꞌꞌͼԝᴒͼⱲ꞉ᴣᴒꜜͼ꞉ꜜͼᴡⱳᴒͼᴠԜꜛᴒͼᴢꜞꜞᴒᴟͼԜᴟꜛԓͼᴤ꞉ᴡⱳͼԜᴡͼꞌᴒԜᴠᴡͼ᷉ͼᴐꜛͼᴠᴒꜞԜᴟԜᴡ꞉ꜝꜜͼԝᴒᴡᴤᴒᴒꜜͼᴒԜᴐⱳͼ
꞉ꜜ꞊ᴒᴐᴡ꞉ꜝꜜͼᴠ꞉ᴡᴒ᷅
5.1.2
Placebo
͟ꞌԜᴐᴒԝꜝͼᴐꜝꜜᴠ꞉ᴠᴡᴠͼꜝⱱͼᴡⱳᴒͼ꞉ꜜԜᴐᴡ꞉ᴣᴒͼⱱꜝᴟꜛᴢꞌԜᴡ꞉ꜝꜜͼꜝⱱͼᴡⱳᴒͼᴡᴒᴠᴡͼꜞᴟꜝᴑᴢᴐᴡⱡͼ᷊᷇ͼꜛꜚͼᴠꜝᴑ꞉ᴢꜛͼꜞⱳꜝᴠꜞⱳԜᴡᴒͼ
ᴑ꞉ԝԜᴠ꞉ᴐͼᴑ꞉ⱳᴦᴑᴟԜᴡᴒԓͼ᷈Ⱡ᷅⅍ꜛꜚͼᴐ꞉ᴡᴟ꞉ᴐͼԜᴐ꞉ᴑԓͼ᷿᷇ͼꜛꜚͼⱳ꞉ᴠᴡ꞉ᴑ꞉ꜜᴒԓͼⱠ᷇ͼꜛꜚͼᴠꜝᴑ꞉ᴢꜛͼᴐⱳꞌꜝᴟ꞉ᴑᴒԓͼꜞⱶͼ⅍᷅᷇ͼᴤ꞉ᴡⱳͼ
᷇᷅᷇᷈Ӽͼ͟ꜝꞌᴦᴠꜝᴟԝԜᴡᴒ˲᷇᷅ͼ
͟ꞌԜᴐᴒԝꜝͼᴑꜝᴠᴒᴠͼᴤ꞉ꞌꞌͼԝᴒͼԜᴑꜛ꞉ꜜ꞉ᴠᴡᴒᴟᴒᴑͼᴡꜝͼᴠᴢԝ꞊ᴒᴐᴡᴠͼᴟԜꜜᴑꜝꜛ꞉ᴧᴒᴑͼᴡꜝͼᴡⱳᴒͼꜞꞌԜᴐᴒԝꜝͼᴡᴟᴒԜᴡꜛᴒꜜᴡͼԜᴟꜛͼԜꜜᴑͼ꞉ꜜͼ
ԝᴒᴡᴤᴒᴒꜜͼᴑꜝᴠᴒᴠͼꜝⱱͼⱫᴅ᷄᷉Ⱡ᷊᷇ͼⱱꜝᴟͼᴠᴢԝ꞊ᴒᴐᴡᴠͼᴟԜꜜᴑꜝꜛ꞉ᴧᴒᴑͼᴡꜝͼᴡⱳᴒͼ᷊᷇᷇ͼꜛⱲͼꜝᴟͼ᷿᷈᷇ͼꜛⱲͼⱫᴅ᷄᷉Ⱡ᷊᷇ͼᴒᴣᴒᴟᴦͼ᷾ͼ
ᴤᴒᴒꞋᴠͼᴡᴟᴒԜᴡꜛᴒꜜᴡͼԜᴟꜛᴠԓͼԜᴐᴐꜝᴟᴑ꞉ꜜⱲͼᴡꜝͼᴡⱳᴒͼᴑꜝᴠ꞉ꜜⱲͼᴠᴐⱳᴒᴑᴢꞌᴒͼ꞉ꜜͼᴁԜԝꞌᴒ᷉᷅ͼ
ⱴꜝᴟͼᴒԜᴐⱳͼꜞꞌԜᴐᴒԝꜝͼᴑꜝᴠᴒԓͼᴒԜᴐⱳͼᴠᴢԝ꞊ᴒᴐᴡͼᴤ꞉ꞌꞌͼᴟᴒᴐᴒ꞉ᴣᴒͼԜͼᴡꜝᴡԜꞌͼꜝⱱͼ᷉ͼꜛꜙԓͼᴑ꞉ᴣ꞉ᴑᴒᴑͼ꞉ꜜᴡꜝͼ᷉ᴠᴒꜞԜᴟԜᴡᴒͼ᷈᷅᷇ꜛꜙͼ
ᴀⱪͼ꞉ꜜ꞊ᴒᴐᴡ꞉ꜝꜜᴠͼꜝⱱͼꜞꞌԜᴐᴒԝꜝ᷅ͼᴁⱳᴒͼ᷉ͼ꞉ꜜ꞊ᴒᴐᴡ꞉ꜝꜜᴠͼᴤ꞉ꞌꞌͼԝᴒͼⱲ꞉ᴣᴒꜜͼ꞉ꜜͼᴡⱳᴒͼᴠԜꜛᴒͼᴢꜞꜞᴒᴟͼԜᴟꜛԓͼᴤ꞉ᴡⱳͼԜᴡͼꞌᴒԜᴠᴡͼ᷉ͼᴐꜛͼ
ᴠᴒꜞԜᴟԜᴡ꞉ꜝꜜͼԝᴒᴡᴤᴒᴒꜜͼᴒԜᴐⱳͼ꞉ꜜ꞊ᴒᴐᴡ꞉ꜝꜜͼᴠ꞉ᴡᴒ᷅
5.2
Dosing and Follow-Up Schedule
ⱫᴒᴡԜ꞉ꞌᴠͼꜝⱱͼᴠᴢԝ꞊ᴒᴐᴡͼᴑꜝᴠ꞉ꜜⱲͼԜꜜᴑͼⱱꜝꞌꞌꜝᴤ᷄ᴢꜞͼԜᴟᴒͼ꞉ꜜᴐꞌᴢᴑᴒᴑͼ꞉ꜜͼᴡⱳᴒͼᴀᴡᴢᴑᴦͼⱨᴐᴡ꞉ᴣ꞉ᴡ꞉ᴒᴠͼᴀᴐⱳᴒᴑᴢꞌᴒԓͼᴁԜԝꞌᴒͼ᷈.
5.3
Method of Assigning Subjects to Treatment Groups
ᴀᴢԝ꞊ᴒᴐᴡᴠͼꜛᴒᴒᴡ꞉ꜜⱲͼԜꞌꞌͼᴒꞌ꞉Ⱳ꞉ԝ꞉ꞌ꞉ᴡᴦͼᴐᴟ꞉ᴡᴒᴟ꞉Ԝͼᴤ꞉ꞌꞌͼԝᴒͼᴒꜜᴟꜝꞌꞌᴒᴑͼ꞉ꜜͼᴡⱳᴒͼᴠᴡᴢᴑᴦͼԜꜜᴑͼᴠᴒꜟᴢᴒꜜᴡ꞉ԜꞌꞌᴦͼԜᴠᴠ꞉ⱲꜜᴒᴑͼԜꜜͼ
꞉ᴑᴒꜜᴡ꞉ⱱ꞉ᴐԜᴡ꞉ꜝꜜͼꜜᴢꜛԝᴒᴟ᷅ͼᴀᴢԝ꞊ᴒᴐᴡᴠͼᴤ꞉ꞌꞌͼԝᴒͼԜᴠᴠ꞉ⱲꜜᴒᴑͼᴡꜝͼꜝꜜᴒͼꜝⱱͼᴡⱳᴒͼⱫᴅ᷄᷉Ⱡ᷊᷇ͼꜝᴟͼꜞꞌԜᴐᴒԝꜝͼᴡᴟᴒԜᴡꜛᴒꜜᴡͼ
Ⱳᴟꜝᴢꜞᴠͼᴣ꞉ԜͼԜꜜͼⱷꜜᴡᴒᴟԜᴐᴡ꞉ᴣᴒͼᴄᴒԝ᷄ԝԜᴠᴒᴑͼϸԜꜜᴑꜝꜛ꞉ᴧԜᴡ꞉ꜝꜜͼᴀᴦᴠᴡᴒꜛͼӿⱷᴄϸᴀԐ᷅ͼᴂᴠᴒͼꜝⱱͼᴡⱳᴒͼⱷᴄϸᴀͼᴤ꞉ꞌꞌͼԝᴒͼ
ꜝᴢᴡꞌ꞉ꜜᴒᴑͼ꞉ꜜͼᴡⱳᴒͼ꜡ꜞᴒᴟԜᴡ꞉ꜝꜜᴠͼꜚԜꜜᴢԜꞌ᷅

Ⱬᴅ᷄᷉Ⱡ᷊᷇
ⱪꞌ꞉ꜜ꞉ᴐԜꞌͼᴁᴟ꞉Ԝꞌͼ͟ᴟꜝᴡꜝᴐꜝꞌⱡͼⱫᴅ᷄᷉Ⱡ᷊᷊᷇᷄᷇
ⱨꜛᴒꜜᴑꜛᴒꜜᴡͼ᷊᷅᷇ͼⱴ꞉ꜜԜꞌⱡͼ᷇ⱠͼꜗԜꜜᴢԜᴟᴦ᷉᷇᷈ⅎ
ⱪꜝꜜⱱ꞉ᴑᴒꜜᴡ꞉Ԝꞌ
͟ԜⱲᴒͼ᷾⅍
ⱫᴦԜᴥͼⱪꜝᴟꜞ᷅
5.4
Blinding and Unblinding
ᴀᴢԝ꞊ᴒᴐᴡᴠͼᴤ꞉ꞌꞌͼԝᴒͼᴟԜꜜᴑꜝꜛ꞉ᴧᴒᴑͼᴡꜝͼᴟᴒᴐᴒ꞉ᴣᴒͼ᷊᷇᷇ͼꜛⱲͼⱫᴅ᷄᷉Ⱡ᷊᷇ͼᴒᴣᴒᴟᴦͼ᷉ͼᴤᴒᴒꞋᴠԓͼ᷊᷇᷇ͼꜛⱲͼⱫᴅ᷄᷉Ⱡ᷊᷇ͼᴒᴣᴒᴟᴦͼ
᷾ͼᴤᴒᴒꞋᴠԓͼ᷿᷈᷇ͼꜛⱲͼⱫᴅ᷄᷉Ⱡ᷊᷇ͼᴒᴣᴒᴟᴦͼ᷾ͼᴤᴒᴒꞋᴠͼꜝᴟͼꜞꞌԜᴐᴒԝꜝͼᴒᴣᴒᴟᴦͼ᷉ͼᴤᴒᴒꞋᴠͼ꞉ꜜͼԜͼᴑꜝᴢԝꞌᴒ᷄ԝꞌ꞉ꜜᴑͼⱱԜᴠⱳ꞉ꜝꜜ᷅ͼ
ᴀᴢԝ꞊ᴒᴐᴡᴠԓͼᴐԜᴟᴒⱲ꞉ᴣᴒᴟᴠͼⱱꜝᴟͼᴠᴢԝ꞊ᴒᴐᴡᴠͼᴢꜜᴑᴒᴟͼ᷈˲ͼᴦᴒԜᴟᴠͼꜝⱱͼԜⱲᴒԓͼⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟᴠͼԜꜜᴑͼᴠ꞉ᴡᴒͼꜞᴒᴟᴠꜝꜜꜜᴒꞌͼᴤ꞉ꞌꞌͼԝᴒͼ
ԝꞌ꞉ꜜᴑᴒᴑͼᴡꜝͼᴡⱳᴒͼᴡᴟᴒԜᴡꜛᴒꜜᴡͼԜᴑꜛ꞉ꜜ꞉ᴠᴡᴒᴟᴒᴑͼᴢꜜᴡ꞉ꞌͼᴡⱳᴒͼᴠᴡᴢᴑᴦͼ꞉ᴠͼᴐꜝꜛꜞꞌᴒᴡᴒ᷅ͼᴁⱳᴒͼᴀꜞꜝꜜᴠꜝᴟͼᴤ꞉ꞌꞌͼԝᴒͼԝꞌ꞉ꜜᴑᴒᴑͼᴡꜝͼ
ᴡⱳᴒͼᴡᴟᴒԜᴡꜛᴒꜜᴡͼԜᴑꜛ꞉ꜜ꞉ᴠᴡᴒᴟᴒᴑͼᴢꜜᴡ꞉ꞌͼԜꞌꞌͼᴠᴢԝ꞊ᴒᴐᴡͼ꞉ꜜᴣꜝꞌᴣᴒꜛᴒꜜᴡͼ꞉ꜜͼᴡⱳᴒͼᴡᴟᴒԜᴡꜛᴒꜜᴡͼꜞᴒᴟ꞉ꜝᴑͼ꞉ᴠͼᴐꜝꜛꜞꞌᴒᴡᴒͼԜꜜᴑͼ
ꜞᴟ꞉ꜛԜᴟᴦͼᴠᴡԜᴡ꞉ᴠᴡ꞉ᴐԜꞌͼԜꜜԜꞌᴦᴠᴒᴠͼⱳԜᴣᴒͼԝᴒᴒꜜͼᴐꜝꜜᴑᴢᴐᴡᴒᴑ᷅
ᴁⱳᴒͼᴡᴟᴒԜᴡꜛᴒꜜᴡͼᴐꜝᴑᴒͼⱱꜝᴟͼԜꜜͼ꞉ꜜᴑ꞉ᴣ꞉ᴑᴢԜꞌͼꜞԜᴡ꞉ᴒꜜᴡͼꜛԜᴦͼꜝꜜꞌᴦͼԝᴒͼԝᴟꜝꞋᴒꜜͼԝᴦͼᴡⱳᴒͼⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟͼꜝᴟͼᴀꜞꜝꜜᴠꜝᴟͼ
ꜝᴟͼᴡⱳᴒͼⱫᴀꜚⱩͼⱱꜝᴟͼᴟᴒԜᴠꜝꜜᴠͼꜝⱱͼꜞԜᴡ꞉ᴒꜜᴡͼᴠԜⱱᴒᴡᴦͼꜝᴟͼ꞉ꜜͼԜꜜͼᴒꜛᴒᴟⱲᴒꜜᴐᴦͼᴤⱳᴒꜜͼꞋꜜꜝᴤꞌᴒᴑⱲᴒͼꜝⱱͼᴡⱳᴒͼᴠᴡᴢᴑᴦͼᴑᴟᴢⱲͼ
Ԝᴑꜛ꞉ꜜ꞉ᴠᴡᴒᴟᴒᴑͼᴤꜝᴢꞌᴑͼԝᴒͼ꞉ꜛꜞꜝᴟᴡԜꜜᴡͼⱱꜝᴟͼᴡⱳᴒᴡᴟᴒԜᴡꜛᴒꜜᴡͼꜝⱱͼᴡⱳᴒͼꜞԜᴡ꞉ᴒꜜᴡ᷅ͼ
ᴁⱳᴒͼⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟͼꜛᴢᴠᴡͼᴑꜝᴐᴢꜛᴒꜜᴡͼᴡⱳᴒͼᴑԜᴡᴒԓͼᴡ꞉ꜛᴒͼԜꜜᴑͼᴟᴒԜᴠꜝꜜͼⱱꜝᴟͼᴡⱳᴒͼᴐꜝᴑᴒͼԝᴟᴒԜꞋ᷅ͼᴁⱳᴒͼⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟͼ
ᴠⱳꜝᴢꞌᴑͼⱱꜝꞌꞌꜝᴤͼᴡⱳᴒͼ꞉ꜜᴠᴡᴟᴢᴐᴡ꞉ꜝꜜᴠͼᴤ꞉ᴡⱳ꞉ꜜͼᴡⱳᴒͼⱷᴄϸᴀͼᴀᴦᴠᴡᴒꜛͼᴠⱳꜝᴢꞌᴑͼԜͼᴐꜝᴑᴒͼԝᴟᴒԜꞋͼԝᴒͼᴟᴒꜟᴢ꞉ᴟᴒᴑ᷅ͼⱷꜜͼᴡⱳᴒͼ
ᴐԜᴠᴒͼꜝⱱͼԜͼᴐꜝꜜᴐᴒᴟꜜ꞉ꜜⱲͼᴑᴟᴢⱲ᷄ᴟᴒꞌԜᴡᴒᴑͼᴠԜⱱᴒᴡᴦᴒᴣᴒꜜᴡԓͼᴡⱳᴒͼⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟͼⱳԜᴠͼᴡⱳᴒͼԜԝ꞉ꞌ꞉ᴡᴦͼᴡꜝͼᴐꜝꜜᴡԜᴐᴡͼԜꜜᴑͼ
ᴐꜝꜜᴠᴢꞌᴡͼᴤ꞉ᴡⱳͼᴡⱳᴒͼꜚᴒᴑ꞉ᴐԜꞌͼꜚꜝꜜ꞉ᴡꜝᴟ᷅ͼⱷꜜͼᴒꜛᴒᴟⱲᴒꜜᴐᴦͼᴠ꞉ᴡᴢԜᴡ꞉ꜝꜜᴠԓͼᴡⱳᴒͼⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟͼꜛԜᴦͼԝᴟᴒԜꞋͼᴡⱳᴒͼ
ᴡᴟᴒԜᴡꜛᴒꜜᴡͼᴐꜝᴑᴒͼ꞉ꜛꜛᴒᴑ꞉ԜᴡᴒꞌᴦͼꜝᴟͼԜᴠͼꜟᴢ꞉ᴐꞋꞌᴦͼԜᴠͼꜞꜝᴠᴠ꞉ԝꞌᴒͼ꞉ⱱͼⱳᴒ᷆ᴠⱳᴒͼⱱ꞉ꜜᴑᴠͼ꞉ᴡͼ꞉ᴠͼ꞉ꜜͼᴡⱳᴒͼԝᴒᴠᴡͼ꞉ꜜᴡᴒᴟᴒᴠᴡͼꜝⱱͼᴡⱳᴒͼ
ᴡᴟ꞉Ԝꞌͼᴠᴢԝ꞊ᴒᴐᴡ᷅ͼᴁⱳᴒͼⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟͼⱳԜᴠͼᴢꜜᴟᴒᴠᴡᴟ꞉ᴐᴡᴒᴑͼԜꜜᴑͼ꞉ꜛꜛᴒᴑ꞉ԜᴡᴒͼԜᴐᴐᴒᴠᴠͼᴡꜝͼԝᴟᴒԜꞋͼᴡⱳᴒͼᴡᴟᴒԜᴡꜛᴒꜜᴡͼᴐꜝᴑᴒͼ
ᴡⱳᴟꜝᴢⱲⱳͼᴡⱳᴒͼⱷᴄϸᴀͼᴀᴦᴠᴡᴒꜛ᷅
ᴁⱳᴒͼⱫԜᴡԜͼԜꜜᴑͼᴀԜⱱᴒᴡᴦͼꜚꜝꜜ꞉ᴡꜝᴟ꞉ꜜⱲͼⱩꜝԜᴟᴑͼӿⱫᴀꜚⱩԐԓͼ꞉ꜜͼᴐꜝꜜᴠᴢꞌᴡԜᴡ꞉ꜝꜜͼᴤ꞉ᴡⱳͼᴡⱳᴒͼꜚᴒᴑ꞉ᴐԜꞌͼꜚꜝꜜ꞉ᴡꜝᴟԓͼꜛԜᴦͼ
Ԝꞌᴠꜝͼᴟᴒꜟᴢᴒᴠᴡͼᴢꜜԝꞌ꞉ꜜᴑ꞉ꜜⱲͼꜝⱱͼԜꜜͼ꞉ꜜᴑ꞉ᴣ꞉ᴑᴢԜꞌͼꜞԜᴡ꞉ᴒꜜᴡᶳᴠͼᴡᴟᴒԜᴡꜛᴒꜜᴡͼԜᴠᴠ꞉ⱲꜜꜛᴒꜜᴡͼⱱꜝᴟͼᴟᴒԜᴠꜝꜜᴠͼꜝⱱͼᴠԜⱱᴒᴡᴦ᷅ͼ
ⱷꜜͼᴡⱳᴒͼᴒᴣᴒꜜᴡͼꜝⱱͼԜͼᴑᴟᴢⱲ᷄ᴟᴒꞌԜᴡᴒᴑԓͼᴠᴒᴟ꞉ꜝᴢᴠԓͼᴢꜜᴒᴥꜞᴒᴐᴡᴒᴑͼⱨⱬԓͼᴡⱳᴒͼᴀꜞꜝꜜᴠꜝᴟᶳᴠͼ͟ⱳԜᴟꜛԜᴐꜝᴣ꞉Ⱳ꞉ꞌԜꜜᴐᴒͼ
ⱫᴒꜞԜᴟᴡꜛᴒꜜᴡͼᴤ꞉ꞌꞌͼԝᴒͼꜞᴟꜝᴣ꞉ᴑᴒᴑͼᴤ꞉ᴡⱳͼᴡⱳᴒͼᴡᴟᴒԜᴡꜛᴒꜜᴡͼԜᴠᴠ꞉Ⱳꜜꜛᴒꜜᴡͼⱱꜝᴟͼᴡⱳᴒͼᴠᴢԝ꞊ᴒᴐᴡͼⱱꜝᴟͼᴡⱳᴒͼꜞᴢᴟꜞꜝᴠᴒͼꜝⱱͼ
ᴟᴒⱲᴢꞌԜᴡꜝᴟᴦͼᴟᴒꜞꜝᴟᴡ꞉ꜜⱲ᷅
5.5
Prior and Concomitant Therapy
ϸᴒԜᴠꜝꜜԜԝꞌᴒͼᴒⱱⱱꜝᴟᴡᴠͼᴤ꞉ꞌꞌͼԝᴒͼꜛԜᴑᴒͼᴡꜝͼᴑᴒᴡᴒᴟꜛ꞉ꜜᴒͼԜꞌꞌͼᴟᴒꞌᴒᴣԜꜜᴡͼᴡᴟᴒԜᴡꜛᴒꜜᴡᴠͼᴟᴒᴐᴒ꞉ᴣᴒᴑͼԝᴦͼᴡⱳᴒͼᴠᴢԝ꞊ᴒᴐᴡͼⱱᴟꜝꜛͼ
ᴡⱳᴒͼᴡ꞉ꜛᴒͼꜝⱱͼᴠᴐᴟᴒᴒꜜ꞉ꜜⱲͼᴢꜞͼᴡꜝͼԜᴑꜛ꞉ꜜ꞉ᴠᴡᴟԜᴡ꞉ꜝꜜͼꜝⱱͼᴡⱳᴒͼⱱ꞉ᴟᴠᴡͼᴑꜝᴠᴒͼꜝⱱͼⱷꜚ᷅͟ͼ
ⱨꞌꞌͼ꞉ꜜⱱꜝᴟꜛԜᴡ꞉ꜝꜜͼꜝꜜͼᴐꜝꜜᴐꜝꜛ꞉ᴡԜꜜᴡͼᴡⱳᴒᴟԜꜞᴦͼⱱᴟꜝꜛͼᴡⱳᴒͼᴡ꞉ꜛᴒͼꜝⱱͼⱱ꞉ᴟᴠᴡͼᴑꜝᴠᴒͼꜝⱱͼⱷꜚ͟ͼᴡⱳᴟꜝᴢⱲⱳͼᴡⱳᴒͼⱱ꞉ꜜԜꞌͼ
ᴠᴡᴢᴑᴦͼᴣ꞉ᴠ꞉ᴡͼӿ꞉ꜜᴐꞌᴢᴑ꞉ꜜⱲͼԜꞌꞌͼꜞᴟᴒᴠᴐᴟ꞉ꜞᴡ꞉ꜝꜜ᷆ꜜꜝꜜ᷄ꜞᴟᴒᴠᴐᴟ꞉ꜞᴡ꞉ꜝꜜͼꜛᴒᴑ꞉ᴐԜᴡ꞉ꜝꜜᴠԓͼⱳᴒᴟԝԜꞌͼꜛᴒᴑ꞉ᴐԜᴡ꞉ꜝꜜᴠͼԜꜜᴑͼ
ᴣ꞉ᴡԜꜛ꞉ꜜͼᴠᴢꜞꜞꞌᴒꜛᴒꜜᴡᴠԐͼꜛᴢᴠᴡͼԝᴒͼᴟᴒᴐꜝᴟᴑᴒᴑͼꜝꜜͼᴡⱳᴒͼᴠᴢԝ꞊ᴒᴐᴡᶳᴠͼᴒꞌᴒᴐᴡᴟꜝꜜ꞉ᴐͼⱪԜᴠᴒͼϸᴒꜞꜝᴟᴡͼⱴꜝᴟꜛͼӿᴒⱪϸⱴԐͼ
Ԝꜜᴑͼᴠⱳꜝᴢꞌᴑͼ꞉ꜜᴐꞌᴢᴑᴒͼᴡⱳᴒͼꜜԜꜛᴒͼꜝⱱͼᴡⱳᴒͼꜞᴟꜝᴐᴒᴑᴢᴟᴒͼꜝᴟͼᴑᴟᴢⱲͼԜꜜᴑͼᴑᴢᴟԜᴡ꞉ꜝꜜͼꜝⱱͼᴡⱳᴒͼᴡᴟᴒԜᴡꜛᴒꜜᴡͼӿᴠᴡԜᴟᴡͼԜꜜᴑͼ
ᴠᴡꜝꜞͼᴑԜᴡᴒᴠԐ᷅ͼⱪꜝꜜᴐꜝꜛ꞉ᴡԜꜜᴡͼᴡᴟᴒԜᴡꜛᴒꜜᴡᴠͼӿꜜꜝꜜ᷄ꜞⱳԜᴟꜛԜᴐꜝꞌꜝⱲ꞉ᴐԜꞌͼᴡᴟᴒԜᴡꜛᴒꜜᴡᴠԐͼ꞉ꜜᴐꞌᴢᴑᴒͼԜꜜᴦͼᴠᴢᴟⱲ꞉ᴐԜꞌͼꜝᴟͼ
ᴑ꞉ԜⱲꜜꜝᴠᴡ꞉ᴐͼꜞᴟꜝᴐᴒᴑᴢᴟᴒᴠ᷅
5.5.1
Allowed Therapies
ᴁⱳᴒͼⱱꜝꞌꞌꜝᴤ꞉ꜜⱲͼᴡⱳᴒᴟԜꜞ꞉ᴒᴠͼԜᴟᴒͼԜꞌꞌꜝᴤᴒᴑͼᴑᴢᴟ꞉ꜜⱲͼᴡⱳᴒͼᴠᴡᴢᴑᴦⱡ
ᶄ
ᴁⱳᴒᴟԜꜞ꞉ᴒᴠͼⱱꜝᴟͼᴐꜝ᷄ᴒᴥ꞉ᴠᴡ꞉ꜜⱲͼᴐꜝꜜᴑ꞉ᴡ꞉ꜝꜜᴠԓͼ꞉ꜜᴐꞌᴢᴑ꞉ꜜⱲͼᴡⱳꜝᴠᴒͼⱱꜝᴟͼԜᴐᴢᴡᴒͼԜᴡᴡԜᴐꞋᴠͼꜝⱱͼⱶⱨⱬԓͼԜᴟᴒͼꜞᴒᴟꜛ꞉ᴡᴡᴒᴑͼ
꞉ⱱͼꜜꜝᴡͼᴒᴥᴐꞌᴢᴑᴒᴑͼ꞉ꜜͼᴀᴒᴐᴡ꞉ꜝꜜͼ᷿᷿᷅᷅᷉᷅ͼⱨᴐᴢᴡᴒͼⱶⱨⱬͼԜᴡᴡԜᴐꞋᴠͼᴑᴢᴟ꞉ꜜⱲͼᴡⱳᴒͼᴠᴡᴢᴑᴦͼԜᴟᴒͼᴡꜝͼԝᴒͼꜛԜꜜԜⱲᴒᴑͼ꞉ꜜͼ
Ԝᴐᴐꜝᴟᴑͼᴤ꞉ᴡⱳͼᴡⱳᴒͼⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟᶳᴠͼᴢᴠᴢԜꞌͼᴐԜᴟᴒͼꜝⱱͼᴡⱳᴒ꞉ᴟͼꜞԜᴡ꞉ᴒꜜᴡᴠԓͼ꞉ꜜᴐꞌᴢᴑ꞉ꜜⱲͼᴢᴠᴒͼꜝⱱͼԜᴐᴢᴡᴒͼԜᴡᴡԜᴐꞋͼ

Ⱬᴅ᷄᷉Ⱡ᷊᷇
ⱪꞌ꞉ꜜ꞉ᴐԜꞌͼᴁᴟ꞉Ԝꞌͼ͟ᴟꜝᴡꜝᴐꜝꞌⱡͼⱫᴅ᷄᷉Ⱡ᷊᷊᷇᷄᷇
ⱨꜛᴒꜜᴑꜛᴒꜜᴡͼ᷊᷅᷇ͼⱴ꞉ꜜԜꞌⱡͼ᷇ⱠͼꜗԜꜜᴢԜᴟᴦ᷉᷇᷈ⅎ
ⱪꜝꜜⱱ꞉ᴑᴒꜜᴡ꞉Ԝꞌ
͟ԜⱲᴒͼ᷾ⅎ
ⱫᴦԜᴥͼⱪꜝᴟꜞ᷅
ᴡⱳᴒᴟԜꜞ꞉ᴒᴠͼᴡⱳԜᴡͼᴡⱳᴒͼⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟͼᴑᴒᴒꜛᴠͼԜᴠͼꜛᴒᴑ꞉ᴐԜꞌꞌᴦͼԜꜞꜞᴟꜝꜞᴟ꞉Ԝᴡᴒ᷅ͼᴂᴠᴒͼꜝⱱͼⱪ᷈᷄ⱷ꜠ⱶͼᴤ꞉ꞌꞌͼԝᴒͼ
ꜞᴒᴟꜛ꞉ᴡᴡᴒᴑͼԜᴠͼԜꜜͼԜᴐᴢᴡᴒͼԜᴡᴡԜᴐꞋͼᴡⱳᴒᴟԜꜞᴦͼԝᴢᴡͼꜜꜝᴡͼԜᴠͼԜͼꞌꜝꜜⱲ᷄ᴡᴒᴟꜛͼꜞᴟꜝꜞⱳᴦꞌԜᴥ꞉ᴠ᷅ͼⱨᴑꜛ꞉ꜜ꞉ᴠᴡᴟԜᴡ꞉ꜝꜜͼꜝⱱͼᴡⱳᴒͼ
꞉ꜜᴣᴒᴠᴡ꞉ⱲԜᴡ꞉ꜝꜜԜꞌͼꜞᴟꜝᴑᴢᴐᴡͼԜꜜᴑͼᴠᴡᴢᴑᴦͼꜞᴟꜝᴐᴒᴑᴢᴟᴒᴠͼᴤ꞉ꞌꞌͼᴐꜝꜜᴡ꞉ꜜᴢᴒͼᴤ꞉ᴡⱳꜝᴢᴡͼԜꞌᴡᴒᴟԜᴡ꞉ꜝꜜͼᴡꜝͼᴡⱳᴒͼꜞᴟꜝᴡꜝᴐꜝꞌͼ
ᴠꜞᴒᴐ꞉ⱱ꞉ᴒᴑͼᴠᴡᴢᴑᴦͼᴠᴐⱳᴒᴑᴢꞌᴒԓͼᴒᴣᴒꜜͼ꞉ⱱͼᴡⱳᴒͼꜞԜᴡ꞉ᴒꜜᴡͼᴟᴒᴐᴒ꞉ᴣᴒᴠͼԜꜜᴦͼᴡᴟᴒԜᴡꜛᴒꜜᴡͼⱱꜝᴟͼԜꜜͼⱶⱨⱬͼԜᴡᴡԜᴐꞋ᷅
ᶄ
ᴁⱳᴒͼᴢᴠᴒͼꜝⱱͼᴠⱳꜝᴟᴡ᷄ᴡᴒᴟꜛͼꜞᴟꜝꜞⱳᴦꞌԜᴐᴡ꞉ᴐͼᴡᴟᴒԜᴡꜛᴒꜜᴡͼⱱꜝᴟͼⱶⱨⱬͼᴤ꞉ꞌꞌͼԝᴒͼꜞᴒᴟꜛ꞉ᴡᴡᴒᴑͼ꞉ⱱͼꜛᴒᴑ꞉ᴐԜꞌꞌᴦͼ
꞉ꜜᴑ꞉ᴐԜᴡᴒᴑ᷅
ᶄ
ᴁⱳᴒᴟԜꜞ꞉ᴒᴠͼᴡꜝͼᴡᴟᴒԜᴡͼԜꜜᴦͼⱨⱬᴠͼᴡⱳᴒͼᴠᴢԝ꞊ᴒᴐᴡͼᴒᴥꜞᴒᴟ꞉ᴒꜜᴐᴒᴠͼᴑᴢᴟ꞉ꜜⱲͼᴡⱳᴒͼᴠᴡᴢᴑᴦͼԜᴟᴒͼꜞᴒᴟꜛ꞉ᴡᴡᴒᴑ᷅
5.5.2
Excluded Concomitant Therapies
ᴂᴠᴒͼꜝⱱͼᴡⱳᴒͼⱱꜝꞌꞌꜝᴤ꞉ꜜⱲͼᴡᴟᴒԜᴡꜛᴒꜜᴡᴠͼᴤ꞉ꞌꞌͼꜜꜝᴡͼԝᴒͼꜞᴒᴟꜛ꞉ᴡᴡᴒᴑͼᴑᴢᴟ꞉ꜜⱲͼᴡⱳᴒͼᴠᴡᴢᴑᴦⱡ
ᶄ
ꜙꜝꜜⱲ᷄ᴡᴒᴟꜛͼꜞᴟꜝꜞⱳᴦꞌԜᴥ꞉ᴠͼⱱꜝᴟͼⱶⱨⱬͼӿᴒ᷅Ⱳ᷅ԓͼᴢᴠᴒͼꜝⱱͼⱪ᷈᷄ⱷ꜠ⱶͼⱱꜝᴟͼꞌꜝꜜⱲ᷄ᴡᴒᴟꜛͼꜞᴟꜝꜞⱳᴦꞌԜᴥ꞉ᴠԓͼԜᴡᴡᴒꜜᴢԜᴡᴒᴑͼ
ԜꜜᴑᴟꜝⱲᴒꜜᴠԓͼꜝᴟͼԜꜜᴡ꞉᷄ⱱ꞉ԝᴟ꞉ꜜꜝꞌᴦᴡ꞉ᴐᴠԐ᷅
ᶄ
ⱨꜜⱲ꞉ꜝᴡᴒꜜᴠ꞉ꜜ᷄ᴐꜝꜜᴣᴒᴟᴡ꞉ꜜⱲͼᴒꜜᴧᴦꜛᴒͼӿⱨⱪⱬԐͼ꞉ꜜⱳ꞉ԝ꞉ᴡꜝᴟᴠ᷅
ᶄ
ⱬᴠᴡᴟꜝⱲᴒꜜ᷄ᴐꜝꜜᴡԜ꞉ꜜ꞉ꜜⱲͼꜛᴒᴑ꞉ᴐԜᴡ꞉ꜝꜜᴠͼᴤ꞉ᴡⱳͼᴠᴦᴠᴡᴒꜛ꞉ᴐͼԜԝᴠꜝᴟꜞᴡ꞉ꜝꜜͼӿᴠᴢᴐⱳͼԜᴠͼꜝᴟԜꞌͼᴐꜝꜜᴡᴟԜᴐᴒꜞᴡ꞉ᴣᴒᴠͼꜝᴟͼ
ⱳꜝᴟꜛꜝꜜԜꞌͼᴟᴒꜞꞌԜᴐᴒꜛᴒꜜᴡͼᴡⱳᴒᴟԜꜞᴦԐ᷅
ᶄ
ⱨꜜᴑᴟꜝⱲᴒꜜᴠͼӿᴒ᷅Ⱳ᷅ԓͼᴠᴡԜꜜꜝᴧꜝꞌꜝꞌԓͼᴑԜꜜԜᴧꜝꞌԓͼꜝᴥԜꜜᴑᴟꜝꞌꜝꜜᴒԓͼꜛᴒᴡⱳᴦꞌᴡᴒᴠᴡꜝᴠᴡᴒᴟꜝꜜᴒԓͼᴡᴒᴠᴡꜝᴠᴡᴒᴟꜝꜜᴒԐ᷅
ᶄ
ⱨꜜᴦͼꜝᴡⱳᴒᴟͼ꞉ꜜᴣᴒᴠᴡ꞉ⱲԜᴡ꞉ꜝꜜԜꞌͼᴑᴟᴢⱲͼꜝᴟͼᴑᴒᴣ꞉ᴐᴒ᷅
5.6
Restrictions
5.6.1
Medical Interventions
ꜚᴒᴑ꞉ᴐԜꞌͼ꞉ꜜᴡᴒᴟᴣᴒꜜᴡ꞉ꜝꜜᴠͼᴑᴒᴒꜛᴒᴑͼꜜᴒᴐᴒᴠᴠԜᴟᴦͼԝᴦͼᴡⱳᴒͼⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟͼⱱꜝᴟͼᴡⱳᴒͼⱳᴒԜꞌᴡⱳͼԜꜜᴑͼᴤᴒꞌꞌ᷄ԝᴒ꞉ꜜⱲͼꜝⱱͼᴡⱳᴒͼ
ᴠᴢԝ꞊ᴒᴐᴡͼᴤ꞉ꞌꞌͼꜜꜝᴡͼԝᴒͼᴒᴥᴐꞌᴢᴑᴒᴑͼᴑᴢᴟ꞉ꜜⱲͼᴡⱳ꞉ᴠͼᴠᴡᴢᴑᴦ᷅ͼ
5.6.2
Fluid and Food Intake 
ᴁⱳᴒᴟᴒͼԜᴟᴒͼꜜꜝͼᴟᴒᴠᴡᴟ꞉ᴐᴡ꞉ꜝꜜᴠͼꜝꜜͼⱱꞌᴢ꞉ᴑͼԜꜜᴑͼⱱꜝꜝᴑͼ꞉ꜜᴡԜꞋᴒ᷅ͼᴀᴢԝ꞊ᴒᴐᴡᴠͼꜛԜᴦͼᴐꜝꜜᴡ꞉ꜜᴢᴒͼᴡⱳᴒ꞉ᴟͼᴢᴠᴢԜꞌͼᴑ꞉ᴒᴡԜᴟᴦͼ
ᴟᴒⱲ꞉ꜛᴒꜜᴠ᷅
5.6.3
Activity
ᴁⱳᴒᴟᴒͼԜᴟᴒͼꜜꜝͼԜᴐᴡ꞉ᴣ꞉ᴡᴦͼᴟᴒᴠᴡᴟ꞉ᴐᴡ꞉ꜝꜜᴠ᷅ͼᴀᴢԝ꞊ᴒᴐᴡᴠͼꜛԜᴦͼᴐꜝꜜᴡ꞉ꜜᴢᴒͼᴡⱳᴒ꞉ᴟͼᴢᴠᴢԜꞌͼԜᴐᴡ꞉ᴣ꞉ᴡᴦͼᴟᴒⱲ꞉ꜛᴒꜜᴠ᷅
5.7
Treatment Compliance
ⱨꞌꞌͼᴑꜝᴠᴒᴠͼꜝⱱͼᴡⱳᴒͼⱷꜚ͟ͼᴤ꞉ꞌꞌͼԝᴒͼԜᴑꜛ꞉ꜜ꞉ᴠᴡᴒᴟᴒᴑͼᴑᴢᴟ꞉ꜜⱲͼᴐꞌ꞉ꜜ꞉ᴐͼᴣ꞉ᴠ꞉ᴡᴠͼᴢꜜᴑᴒᴟͼᴡⱳᴒͼᴑ꞉ᴟᴒᴐᴡͼᴠᴢꜞᴒᴟᴣ꞉ᴠ꞉ꜝꜜͼꜝⱱͼᴡⱳᴒͼ
ⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟͼꜝᴟͼꜟᴢԜꞌ꞉ⱱ꞉ᴒᴑͼᴠ꞉ᴡᴒͼꜞᴒᴟᴠꜝꜜꜜᴒꞌͼᴑᴒᴠ꞉ⱲꜜԜᴡᴒᴑͼԝᴦͼᴡⱳᴒͼⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟ᷅ͼ
5.8
Packaging and Labeling
ᴁⱳᴒͼᴡᴒᴠᴡͼꜞᴟꜝᴑᴢᴐᴡᴠͼӿⱫᴅ᷄᷉Ⱡ᷊᷇ͼԜꜜᴑͼꜞꞌԜᴐᴒԝꜝԐͼᴤ꞉ꞌꞌͼԝᴒͼᴠᴢꜞꜞꞌ꞉ᴒᴑͼԝᴦͼᴡⱳᴒͼᴀꜞꜝꜜᴠꜝᴟͼԜꜜᴑͼꜞԜᴐꞋԜⱲᴒᴑͼԜꜜᴑͼ
ꞌԜԝᴒꞌᴒᴑͼԜᴐᴐꜝᴟᴑ꞉ꜜⱲͼᴡꜝͼԜꜞꜞꞌ꞉ᴐԜԝꞌᴒͼꞌꜝᴐԜꞌͼԜꜜᴑͼᴟᴒⱲᴢꞌԜᴡꜝᴟᴦͼᴟᴒꜟᴢ꞉ᴟᴒꜛᴒꜜᴡᴠͼⱱꜝᴟͼ꞉ꜜᴣᴒᴠᴡ꞉ⱲԜᴡ꞉ꜝꜜԜꞌͼᴠᴡᴢᴑ꞉ᴒᴠ᷅

Ⱬᴅ᷄᷉Ⱡ᷊᷇
ⱪꞌ꞉ꜜ꞉ᴐԜꞌͼᴁᴟ꞉Ԝꞌͼ͟ᴟꜝᴡꜝᴐꜝꞌⱡͼⱫᴅ᷄᷉Ⱡ᷊᷊᷇᷄᷇
ⱨꜛᴒꜜᴑꜛᴒꜜᴡͼ᷊᷅᷇ͼⱴ꞉ꜜԜꞌⱡͼ᷇ⱠͼꜗԜꜜᴢԜᴟᴦ᷉᷇᷈ⅎ
ⱪꜝꜜⱱ꞉ᴑᴒꜜᴡ꞉Ԝꞌ
͟ԜⱲᴒͼ᷾˲
ⱫᴦԜᴥͼⱪꜝᴟꜞ᷅
5.9
Storage and Accountability
ⱨꞌꞌͼᴠᴢꜞꜞꞌ꞉ᴒᴠͼꜝⱱͼᴡⱳᴒͼ꞉ꜜᴣᴒᴠᴡ꞉ⱲԜᴡ꞉ꜝꜜԜꞌͼꜞᴟꜝᴑᴢᴐᴡᴠͼӿⱫᴅ᷄᷉Ⱡ᷊᷇ͼԜꜜᴑͼꜞꞌԜᴐᴒԝꜝԐͼꜛᴢᴠᴡͼԝᴒͼᴠᴡꜝᴟᴒᴑͼᴟᴒⱱᴟ꞉ⱲᴒᴟԜᴡᴒᴑͼ
ӿ᷉ᶛⱪͼᴡꜝͼ˲ᶛⱪ᷊᷆⅍ᶛⱴͼᴡꜝͼ᷾⅍ᶛⱴԐͼ꞉ꜜͼᴡⱳᴒͼꜝᴟ꞉Ⱳ꞉ꜜԜꞌͼᴐԜᴟᴡꜝꜜͼԜꜜᴑͼꜞᴟꜝᴡᴒᴐᴡᴒᴑͼⱱᴟꜝꜛͼꞌ꞉Ⱳⱳᴡԓͼ꞉ꜜͼԜͼᴠᴒᴐᴢᴟᴒꞌᴦͼꞌꜝᴐꞋᴒᴑͼ
ԜᴟᴒԜԓͼԜᴐᴐᴒᴠᴠ꞉ԝꞌᴒͼᴡꜝͼԜᴢᴡⱳꜝᴟ꞉ᴧᴒᴑͼꜞᴒᴟᴠꜝꜜᴠͼꜝꜜꞌᴦԓͼᴢꜜᴡ꞉ꞌͼꜜᴒᴒᴑᴒᴑͼⱱꜝᴟͼᴑꜝᴠᴒͼꜞᴟᴒꜞԜᴟԜᴡ꞉ꜝꜜ᷅ͼϷᴢԜꞌ꞉ⱱ꞉ᴒᴑͼᴠ꞉ᴡᴒͼ
ꜞᴒᴟᴠꜝꜜꜜᴒꞌͼᴤ꞉ꞌꞌͼ꞉ꜜᴣᴒꜜᴡꜝᴟᴦͼᴡⱳᴒͼ꞉ꜜᴣᴒᴠᴡ꞉ⱲԜᴡ꞉ꜝꜜԜꞌͼꜞᴟꜝᴑᴢᴐᴡͼᴟᴒᴐᴒ꞉ᴣᴒᴑͼԜꜜᴑͼᴤ꞉ꞌꞌͼꜛԜ꞉ꜜᴡԜ꞉ꜜͼᴟᴒᴐꜝᴟᴑᴠͼꜝⱱͼ
ᴑ꞉ᴠꜞꜝᴠ꞉ᴡ꞉ꜝꜜͼꜝⱱͼᴡⱳᴒͼᴑᴟᴢⱲԓͼ꞉ꜜᴐꞌᴢᴑ꞉ꜜⱲͼᴑԜᴡᴒᴠԓͼꜟᴢԜꜜᴡ꞉ᴡᴦͼԜꜜᴑͼᴢᴠᴒ᷅
5.10
Investigational Medicinal Product Retention at Study Site
ᴁⱳᴒͼⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟͼӿꜝᴟͼᴑᴒᴠ꞉ⱲꜜᴒᴒԐͼ꞉ᴠͼᴟᴒᴠꜞꜝꜜᴠ꞉ԝꞌᴒͼⱱꜝᴟͼꜛԜ꞉ꜜᴡԜ꞉ꜜ꞉ꜜⱲͼԜᴐᴐᴢᴟԜᴡᴒͼԜᴐᴐꜝᴢꜜᴡԜԝ꞉ꞌ꞉ᴡᴦͼᴟᴒᴐꜝᴟᴑᴠͼꜝⱱͼ
ᴡⱳᴒͼⱷꜚ͟ͼᴡⱳᴟꜝᴢⱲⱳꜝᴢᴡͼᴡⱳᴒͼᴐꞌ꞉ꜜ꞉ᴐԜꞌͼᴠᴡᴢᴑᴦ᷅ͼⱨꞌꞌͼⱷꜚ͟ͼᴟᴒᴐᴒ꞉ᴣᴒᴑͼԜᴡͼᴡⱳᴒͼᴠ꞉ᴡᴒͼꜛᴢᴠᴡͼԝᴒͼ꞉ꜜᴣᴒꜜᴡꜝᴟ꞉ᴒᴑͼԜꜜᴑͼ
Ԝᴐᴐꜝᴢꜜᴡᴒᴑͼⱱꜝᴟͼ꞉ꜜͼԜꜜͼԜᴐᴐꜝᴢꜜᴡԜԝ꞉ꞌ꞉ᴡᴦͼꞌꜝⱲͼꜞᴟꜝᴣ꞉ᴑᴒᴑͼԝᴦͼᴡⱳᴒͼᴀꜞꜝꜜᴠꜝᴟ᷅ͼⱨꞌꞌͼᴑ꞉ᴠꜞᴒꜜᴠ꞉ꜜⱲͼԜꜜᴑͼ
ԜᴐᴐꜝᴢꜜᴡԜԝ꞉ꞌ꞉ᴡᴦͼᴟᴒᴐꜝᴟᴑᴠͼᴤ꞉ꞌꞌͼԝᴒͼԜᴣԜ꞉ꞌԜԝꞌᴒͼⱱꜝᴟͼᴀꜞꜝꜜᴠꜝᴟͼᴟᴒᴣ꞉ᴒᴤ᷅ⱷꜚ͟ͼԜᴐᴐꜝᴢꜜᴡԜԝ꞉ꞌ꞉ᴡᴦͼᴤ꞉ꞌꞌͼԝᴒͼᴣᴒᴟ꞉ⱱ꞉ᴒᴑͼ
ᴑᴢᴟ꞉ꜜⱲͼꜝꜜ᷄ᴠ꞉ᴡᴒͼꜛꜝꜜ꞉ᴡꜝᴟ꞉ꜜⱲͼᴣ꞉ᴠ꞉ᴡᴠ᷅
ᴂꜞꜝꜜͼᴡⱳᴒͼᴐꜝꜛꜞꞌᴒᴡ꞉ꜝꜜͼꜝᴟͼᴡᴒᴟꜛ꞉ꜜԜᴡ꞉ꜝꜜͼꜝⱱͼᴡⱳᴒͼᴠᴡᴢᴑᴦԓͼԜꜜᴑͼᴢꜞꜝꜜͼᴤᴟ꞉ᴡᴡᴒꜜͼԜᴢᴡⱳꜝᴟ꞉ᴧԜᴡ꞉ꜝꜜͼⱱᴟꜝꜛͼᴡⱳᴒͼ
ᴀꜞꜝꜜᴠꜝᴟԓͼꜝᴟͼ꞉ᴡᴠͼᴟᴒꜞᴟᴒᴠᴒꜜᴡԜᴡ꞉ᴣᴒԓͼԜꞌꞌͼᴢꜜᴢᴠᴒᴑͼԜꜜᴑ᷆ꜝᴟͼꜞԜᴟᴡ꞉Ԝꞌꞌᴦͼᴢᴠᴒᴑͼⱷꜚ͟ͼᴠⱳꜝᴢꞌᴑͼԝᴒͼᴟᴒᴡᴢᴟꜜᴒᴑͼꜝᴟͼ
ᴑᴒᴠᴡᴟꜝᴦᴒᴑͼԜᴡͼᴡⱳᴒͼ꞉ꜜᴣᴒᴠᴡ꞉ⱲԜᴡ꞉ꜝꜜԜꞌͼᴠ꞉ᴡᴒԓͼԜᴠͼᴠꜞᴒᴐ꞉ⱱ꞉ᴒᴑͼԝᴦͼᴀꜞꜝꜜᴠꜝᴟ᷅ͼⱷᴡͼ꞉ᴠͼᴡⱳᴒⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟᶳᴠͼ
ᴟᴒᴠꜞꜝꜜᴠ꞉ԝ꞉ꞌ꞉ᴡᴦͼᴡꜝͼᴒꜜᴠᴢᴟᴒͼᴡⱳԜᴡͼᴡⱳᴒͼᴀꜞꜝꜜᴠꜝᴟԓͼꜝᴟͼ꞉ᴡᴠͼᴟᴒꜞᴟᴒᴠᴒꜜᴡԜᴡ꞉ᴣᴒԓͼⱳԜᴠͼꜞᴟꜝᴣ꞉ᴑᴒᴑͼᴤᴟ꞉ᴡᴡᴒꜜͼԜᴢᴡⱳꜝᴟ꞉ᴧԜᴡ꞉ꜝꜜͼ
ᴡⱳԜᴡͼꜞᴟꜝᴐᴒᴑᴢᴟᴒᴠͼⱱꜝᴟͼꜞᴟꜝꜞᴒᴟͼᴑ꞉ᴠꜞꜝᴠԜꞌͼꜝⱱͼᴡⱳᴒͼⱷꜚ͟ͼⱳԜᴣᴒͼԝᴒᴒꜜͼᴒᴠᴡԜԝꞌ꞉ᴠⱳᴒᴑԓͼԜꜜᴑͼᴡⱳԜᴡͼԜꜞꜞᴟꜝꜞᴟ꞉Ԝᴡᴒͼ
ᴟᴒᴐꜝᴟᴑᴠͼꜝⱱͼᴡⱳᴒͼᴑ꞉ᴠꜞꜝᴠԜꞌͼԜᴟᴒͼᴑꜝᴐᴢꜛᴒꜜᴡᴒᴑͼԜꜜᴑͼꜛԜ꞉ꜜᴡԜ꞉ꜜᴒᴑ᷅ͼ꜠ꜝͼᴢꜜᴢᴠᴒᴑͼⱷꜚ͟ͼꜛԜᴦͼԝᴒͼᴑ꞉ᴠꜞꜝᴠᴒᴑͼᴢꜜᴡ꞉ꞌͼ
ⱱᴢꞌꞌᴦͼԜᴐᴐꜝᴢꜜᴡᴒᴑͼⱱꜝᴟͼԝᴦͼᴡⱳᴒͼᴀꜞꜝꜜᴠꜝᴟͼꜛꜝꜜ꞉ᴡꜝᴟͼӿꜝᴟͼᴑᴒᴠ꞉ⱲꜜᴒᴒԐ᷅

Ⱬᴅ᷄᷉Ⱡ᷊᷇
ⱪꞌ꞉ꜜ꞉ᴐԜꞌͼᴁᴟ꞉Ԝꞌͼ͟ᴟꜝᴡꜝᴐꜝꞌⱡͼⱫᴅ᷄᷉Ⱡ᷊᷊᷇᷄᷇
ⱨꜛᴒꜜᴑꜛᴒꜜᴡͼ᷊᷅᷇ͼⱴ꞉ꜜԜꞌⱡͼ᷇ⱠͼꜗԜꜜᴢԜᴟᴦ᷉᷇᷈ⅎ
ⱪꜝꜜⱱ꞉ᴑᴒꜜᴡ꞉Ԝꞌ
͟ԜⱲᴒͼ᷾Ⱡ
ⱫᴦԜᴥͼⱪꜝᴟꜞ᷅
6
STUDY PROCEDURES
͟ꞌᴒԜᴠᴒͼᴟᴒⱱᴒᴟͼᴡꜝͼᴡⱳᴒͼᴀᴡᴢᴑᴦͼⱨᴐᴡ꞉ᴣ꞉ᴡ꞉ᴒᴠͼᴀᴐⱳᴒᴑᴢꞌᴒԓͼᴁԜԝꞌᴒͼ᷈᷅
6.1
Informed Consent
ⱷꜜⱱꜝᴟꜛᴒᴑͼⱪꜝꜜᴠᴒꜜᴡͼԜꜜᴑͼⱨᴠᴠᴒꜜᴡͼⱱꜝᴟꜛᴠͼꜛᴢᴠᴡͼԝᴒͼԜꜞꜞᴟꜝᴣᴒᴑͼⱱꜝᴟͼᴢᴠᴒͼԝᴦͼᴡⱳᴒᴟᴒᴣ꞉ᴒᴤ꞉ꜜⱲͼ꞉ꜜᴠᴡ꞉ᴡᴢᴡ꞉ꜝꜜԜꞌͼ
ᴟᴒᴣ꞉ᴒᴤͼԝꜝԜᴟᴑͼӿⱷϸⱩԐԓͼᴟᴒᴠᴒԜᴟᴐⱳͼᴒᴡⱳ꞉ᴐᴠͼԝꜝԜᴟᴑͼӿϸⱬⱩԐͼꜝᴟͼ꞉ꜜᴑᴒꜞᴒꜜᴑᴒꜜᴡͼᴒᴡⱳ꞉ᴐᴠͼᴐꜝꜛꜛ꞉ᴡᴡᴒᴒͼӿⱷⱬⱪԐ᷅ͼ
ⱷꜜⱱꜝᴟꜛᴒᴑͼᴐꜝꜜᴠᴒꜜᴡԓͼԜꜜᴑͼԜᴠᴠᴒꜜᴡͼᴤⱳᴒꜜͼԜꜞꜞꞌ꞉ᴐԜԝꞌᴒԓͼꜛᴢᴠᴡͼԝᴒͼꜝԝᴡԜ꞉ꜜᴒᴑͼⱱꜝᴟͼԜꞌꞌͼᴠᴢԝ꞊ᴒᴐᴡᴠͼꜞԜᴟᴡ꞉ᴐ꞉ꜞԜᴡ꞉ꜜⱲͼ꞉ꜜͼ
ᴡⱳᴒͼᴠᴡᴢᴑᴦͼꜞᴟ꞉ꜝᴟͼᴡꜝͼꜞᴒᴟⱱꜝᴟꜛ꞉ꜜⱲͼԜꜜᴦͼᴠᴡᴢᴑᴦͼᴟᴒꞌԜᴡᴒᴑԜᴐᴡ꞉ᴣ꞉ᴡ꞉ᴒᴠ᷅ͼᴀᴢԝ꞊ᴒᴐᴡᴠͼꜛԜᴦͼᴤ꞉ᴡⱳᴑᴟԜᴤͼᴐꜝꜜᴠᴒꜜᴡͼԜᴡͼԜꜜᴦͼ
ᴡ꞉ꜛᴒ᷅ͼ͟Ԝᴟᴡ꞉ᴐ꞉ꜞԜᴡ꞉ꜝꜜͼ꞉ꜜͼᴡⱳᴒͼᴠᴡᴢᴑᴦͼꜛԜᴦͼԝᴒͼᴡᴒᴟꜛ꞉ꜜԜᴡᴒᴑͼԜᴡͼԜꜜᴦͼᴡ꞉ꜛᴒͼᴤ꞉ᴡⱳꜝᴢᴡͼᴡⱳᴒͼᴠᴢԝ꞊ᴒᴐᴡᶳᴠͼᴐꜝꜜᴠᴒꜜᴡͼԜᴠͼ
ᴑᴒᴡᴒᴟꜛ꞉ꜜᴒᴑͼԝᴦͼᴡⱳᴒͼⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟ᷅
6.2
Eligibility Review
ᴁⱳᴒͼⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟͼꜝᴟͼꜟᴢԜꞌ꞉ⱱ꞉ᴒᴑͼᴠ꞉ᴡᴒͼꜞᴒᴟᴠꜝꜜꜜᴒꞌͼᴤ꞉ꞌꞌͼᴐꜝꜜⱱ꞉ᴟꜛͼᴡⱳԜᴡͼԜꞌꞌͼⱷꜜᴐꞌᴢᴠ꞉ꜝꜜͼԜꜜᴑͼⱬᴥᴐꞌᴢᴠ꞉ꜝꜜͼᴐᴟ꞉ᴡᴒᴟ꞉Ԝͼ
ⱳԜᴣᴒͼԝᴒᴒꜜͼꜛᴒᴡ᷅
6.3
Demographics and Medical History
ⱫᴒꜛꜝⱲᴟԜꜞⱳ꞉ᴐᴠⱡͼᴑԜᴡᴒͼꜝⱱͼԝ꞉ᴟᴡⱳͼӿԜꞌᴡᴒᴟꜜԜᴡ꞉ᴣᴒꞌᴦͼԜⱲᴒͼꜝᴟͼᴦᴒԜᴟͼꜝⱱͼԝ꞉ᴟᴡⱳԓͼ꞉ⱱͼⱱᴢꞌꞌͼᴑԜᴡᴒͼꜝⱱͼԝ꞉ᴟᴡⱳͼ꞉ᴠͼꜜꜝᴡͼԜꞌꞌꜝᴤᴒᴑͼ
ᴡꜝͼԝᴒͼᴐꜝꞌꞌᴒᴐᴡᴒᴑͼⱱꜝᴟͼꞌᴒⱲԜꞌͼᴟᴒԜᴠꜝꜜᴠԐԓͼᴠᴒᴥԓͼᴟԜᴐᴒͼԜꜜᴑͼᴒᴡⱳꜜ꞉ᴐ꞉ᴡᴦͼӿᴤⱳᴒᴟᴒͼꞌꜝᴐԜꞌꞌᴦͼꜞᴒᴟꜛ꞉ᴡᴡᴒᴑԐͼԜꜜᴑͼꜛᴒᴑ꞉ᴐԜꞌͼ
ⱳ꞉ᴠᴡꜝᴟᴦͼᴤ꞉ꞌꞌͼԝᴒͼꜝԝᴡԜ꞉ꜜᴒᴑͼⱱᴟꜝꜛͼᴡⱳᴒͼᴠᴢԝ꞊ᴒᴐᴡͼԜꜜᴑͼᴟᴒᴐꜝᴟᴑᴒᴑͼ꞉ꜜͼᴠꜝᴢᴟᴐᴒͼᴑꜝᴐᴢꜛᴒꜜᴡᴠͼԜꜜᴑͼᴡⱳᴒͼᴒⱪϸⱴ᷅ͼ
ꜚᴒᴑ꞉ᴐԜꞌͼⱳ꞉ᴠᴡꜝᴟᴦͼᴤ꞉ꞌꞌͼᴐԜꜞᴡᴢᴟᴒͼᴡⱳᴒͼᴠᴢԝ꞊ᴒᴐᴡᶳᴠͼᴐᴢᴟᴟᴒꜜᴡͼᴟᴒꞌᴒᴣԜꜜᴡͼꜛᴒᴑ꞉ᴐԜꞌͼᴠᴡԜᴡᴢᴠͼӿᴐᴢᴟᴟᴒꜜᴡͼᴑ꞉ᴠᴒԜᴠᴒͼ
ꜞᴟꜝᴐᴒᴠᴠᴒᴠԐԓͼꜞԜᴠᴡͼᴟᴒꞌᴒᴣԜꜜᴡͼꜛᴒᴑ꞉ᴐԜꞌͼᴠᴡԜᴡᴢᴠͼӿꜞԜᴠᴡͼᴑ꞉ᴠᴒԜᴠᴒͼꜞᴟꜝᴐᴒᴠᴠᴒᴠԐԓͼⱳ꞉ᴠᴡꜝᴟᴦͼꜝⱱͼᴠᴢᴟⱲᴒᴟᴦԓͼԜꞌꞌᴒᴟⱲ꞉ᴒᴠͼԜꜜᴑͼ
ᴐꜝꜜᴐꜝꜛ꞉ᴡԜꜜᴡͼꜛᴒᴑ꞉ᴐԜᴡ꞉ꜝꜜᴠ᷅
6.4
Efficacy Assessments
6.4.1
Primary and Secondary Endpoints
͟ᴟ꞉ꜛԜᴟᴦͼԜꜜᴑͼᴠᴒᴐꜝꜜᴑԜᴟᴦͼᴒⱱⱱ꞉ᴐԜᴐᴦͼᴒꜜᴑꜞꜝ꞉ꜜᴡᴠͼᴤ꞉ꞌꞌͼԝᴒͼԝԜᴠᴒᴑͼꜝꜜͼԜꜜͼᴒⱱⱱ꞉ᴐԜᴐᴦͼᴒᴣԜꞌᴢԜᴡ꞉ꜝꜜͼꜞᴒᴟ꞉ꜝᴑͼ
ᴠꜞԜꜜꜜ꞉ꜜⱲͼⱫԜᴦͼ᷇ͼӿԜⱱᴡᴒᴟͼᴠᴡᴢᴑᴦͼᴑᴟᴢⱲͼԜᴑꜛ꞉ꜜ꞉ᴠᴡᴟԜᴡ꞉ꜝꜜԐͼᴡⱳᴟꜝᴢⱲⱳͼⱫԜᴦͼ᷈˲᷉ԓͼᴢꜜꞌᴒᴠᴠͼꜝᴡⱳᴒᴟᴤ꞉ᴠᴒͼᴠꜞᴒᴐ꞉ⱱ꞉ᴒᴑͼ
Primary Efficacy Endpoint

꜠ᴢꜛԝᴒᴟͼꜝⱱͼⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟ᷄ᴐꜝꜜⱱ꞉ᴟꜛᴒᴑͼⱶⱨⱬͼԜᴡᴡԜᴐꞋᴠͼᴑᴢᴟ꞉ꜜⱲͼᴡⱳᴒͼᴒⱱⱱ꞉ᴐԜᴐᴦͼᴒᴣԜꞌᴢԜᴡ꞉ꜝꜜͼꜞᴒᴟ꞉ꜝᴑͼӿⱫԜᴦͼ᷇ͼ
ᴡⱳᴟꜝᴢⱲⱳͼⱫԜᴦͼ᷈˲᷉Ԑ
Secondary Efficacy Endpoints (rank ordered)
᷈᷅꜠ᴢꜛԝᴒᴟͼꜝⱱͼⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟ᷄ᴐꜝꜜⱱ꞉ᴟꜛᴒᴑͼⱶⱨⱬͼԜᴡᴡԜᴐꞋᴠͼᴟᴒꜟᴢ꞉ᴟ꞉ꜜⱲͼԜᴐᴢᴡᴒͼᴡᴟᴒԜᴡꜛᴒꜜᴡͼᴑᴢᴟ꞉ꜜⱲͼᴡⱳᴒͼᴒⱱⱱ꞉ᴐԜᴐᴦͼ
ᴒᴣԜꞌᴢԜᴡ꞉ꜝꜜͼꜞᴒᴟ꞉ꜝᴑͼӿⱫԜᴦͼ᷇ͼᴡⱳᴟꜝᴢⱲⱳͼⱫԜᴦͼ᷈˲᷉Ԑ
᷉᷅꜠ᴢꜛԝᴒᴟͼꜝⱱͼꜛꜝᴑᴒᴟԜᴡᴒͼꜝᴟͼᴠᴒᴣᴒᴟᴒͼⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟ᷄ᴐꜝꜜⱱ꞉ᴟꜛᴒᴑͼⱶⱨⱬͼԜᴡᴡԜᴐꞋᴠͼᴑᴢᴟ꞉ꜜⱲͼᴡⱳᴒͼᴒⱱⱱ꞉ᴐԜᴐᴦͼ
ᴒᴣԜꞌᴢԜᴡ꞉ꜝꜜͼꜞᴒᴟ꞉ꜝᴑͼӿⱫԜᴦͼ᷇ͼᴡⱳᴟꜝᴢⱲⱳͼⱫԜᴦͼ᷈˲᷉Ԑ
᷊᷅꜠ᴢꜛԝᴒᴟͼꜝⱱͼⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟͼᴐꜝꜜⱱ꞉ᴟꜛᴒᴑͼⱶⱨⱬͼԜᴡᴡԜᴐꞋᴠͼꜝᴐᴐᴢᴟᴟ꞉ꜜⱲͼꜝꜜͼⱫԜᴦͼ᷈᷾ͼԜⱱᴡᴒᴟͼԜᴑꜛ꞉ꜜ꞉ᴠᴡᴟԜᴡ꞉ꜝꜜͼꜝⱱͼ
ᴠᴡᴢᴑᴦͼᴑᴟᴢⱲͼᴡⱳᴟꜝᴢⱲⱳͼⱫԜᴦͼ᷈˲᷉ͼӿⱫԜᴦͼ᷈᷾ͼᴡⱳᴟꜝᴢⱲⱳͼⱫԜᴦͼ᷈˲᷉Ԑ

Ⱬᴅ᷄᷉Ⱡ᷊᷇
ⱪꞌ꞉ꜜ꞉ᴐԜꞌͼᴁᴟ꞉Ԝꞌͼ͟ᴟꜝᴡꜝᴐꜝꞌⱡͼⱫᴅ᷄᷉Ⱡ᷊᷊᷇᷄᷇
ⱨꜛᴒꜜᴑꜛᴒꜜᴡͼ᷊᷅᷇ͼⱴ꞉ꜜԜꞌⱡͼ᷇ⱠͼꜗԜꜜᴢԜᴟᴦ᷉᷇᷈ⅎ
ⱪꜝꜜⱱ꞉ᴑᴒꜜᴡ꞉Ԝꞌ
͟ԜⱲᴒͼ᷿᷇
ⱫᴦԜᴥͼⱪꜝᴟꜞ᷅
Exploratory Efficacy Endpoints

ᴁ꞉ꜛᴒͼᴡꜝͼⱱ꞉ᴟᴠᴡͼⱶⱨⱬͼԜᴡᴡԜᴐꞋͼԜⱱᴡᴒᴟͼⱫԜᴦͼ᷈᷾ԓͼ꞉᷅ᴒ᷅ԓͼᴑᴢᴟԜᴡ꞉ꜝꜜͼᴡⱳԜᴡͼԜͼᴠᴢԝ꞊ᴒᴐᴡͼ꞉ᴠͼԜᴡᴡԜᴐꞋ᷄ⱱᴟᴒᴒͼԜⱱᴡᴒᴟͼⱫԜᴦ᷈᷾
ᶄ
꜠ᴢꜛԝᴒᴟͼꜝⱱͼⱳ꞉Ⱳⱳ᷄ꜛꜝᴟԝ꞉ᴑ꞉ᴡᴦͼⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟ᷄ᴐꜝꜜⱱ꞉ᴟꜛᴒᴑͼⱶⱨⱬͼԜᴡᴡԜᴐꞋᴠͼᴑᴢᴟ꞉ꜜⱲͼᴡⱳᴒͼᴒⱱⱱ꞉ᴐԜᴐᴦͼ
ᴒᴣԜꞌᴢԜᴡ꞉ꜝꜜͼꜞᴒᴟ꞉ꜝᴑⱢͼԜͼⱳ꞉Ⱳⱳ᷄ꜛꜝᴟԝ꞉ᴑ꞉ᴡᴦͼⱶⱨⱬͼԜᴡᴡԜᴐꞋͼ꞉ᴠͼᴑᴒⱱ꞉ꜜᴒᴑͼԜᴠͼԜꜜᴦͼԜᴡᴡԜᴐꞋͼᴡⱳԜᴡͼⱳԜᴠͼԜᴡͼꞌᴒԜᴠᴡͼꜝꜜᴒͼ
ꜝⱱͼᴡⱳᴒͼⱱꜝꞌꞌꜝᴤ꞉ꜜⱲͼᴐⱳԜᴟԜᴐᴡᴒᴟ꞉ᴠᴡ꞉ᴐᴠⱡͼᴠᴒᴣᴒᴟᴒԓͼᴟᴒᴠᴢꞌᴡᴠͼ꞉ꜜͼⱳꜝᴠꜞ꞉ᴡԜꞌ꞉ᴧԜᴡ꞉ꜝꜜͼӿᴒᴥᴐᴒꜞᴡͼⱳꜝᴠꜞ꞉ᴡԜꞌ꞉ᴧԜᴡ꞉ꜝꜜͼⱱꜝᴟͼ
ꜝԝᴠᴒᴟᴣԜᴡ꞉ꜝꜜͼⱣͼ᷉᷾ͼⱳꜝᴢᴟᴠԐԓͼⱳᴒꜛꜝᴑᴦꜜԜꜛ꞉ᴐԜꞌꞌᴦͼᴠ꞉Ⱳꜜ꞉ⱱ꞉ᴐԜꜜᴡͼӿᴠᴦᴠᴡꜝꞌ꞉ᴐͼԝꞌꜝꜝᴑͼꜞᴟᴒᴠᴠᴢᴟᴒͼⱣͼⱠ᷇ԓͼᴟᴒꜟᴢ꞉ᴟᴒᴠͼ
ⱷᴃͼⱳᴦᴑᴟԜᴡ꞉ꜝꜜԓͼꜝᴟͼԜᴠᴠꜝᴐ꞉Ԝᴡᴒᴑͼᴤ꞉ᴡⱳͼᴠᴦꜜᴐꜝꜞᴒͼꜝᴟͼꜜᴒԜᴟ᷄ᴠᴦꜜᴐꜝꜞᴒԐͼꜝᴟͼꞌԜᴟᴦꜜⱲᴒԜꞌ᷅
6.4.2
HAE Attack Information Collection
ᴁⱳᴒͼᴐꜝꞌꞌᴒᴐᴡ꞉ꜝꜜԓͼᴟᴒꜞꜝᴟᴡ꞉ꜜⱲͼԜꜜᴑͼԜᴠᴠᴒᴠᴠꜛᴒꜜᴡͼꜝⱱͼԜᴡᴡԜᴐꞋᴠͼ꞉ꜜͼᴡⱳ꞉ᴠͼᴠᴡᴢᴑᴦͼᴤ꞉ꞌꞌͼԝᴒͼᴑꜝꜜᴒͼ꞉ꜜͼԜᴐᴐꜝᴟᴑԜꜜᴐᴒͼᴤ꞉ᴡⱳͼ
ᴡⱳᴒͼⱶⱨⱬͼⱨᴡᴡԜᴐꞋͼⱨᴠᴠᴒᴠᴠꜛᴒꜜᴡͼԜꜜᴑͼϸᴒꜞꜝᴟᴡ꞉ꜜⱲͼ͟ᴟꜝᴐᴒᴑᴢᴟᴒᴠͼӿⱶⱨⱨϸ͟Ԑͼӿⱨꜞꜞᴒꜜᴑ꞉ᴥͼ᷾Ԑ᷅ͼᴀ꞉ᴡᴒͼꜞᴒᴟᴠꜝꜜꜜᴒꞌͼ
ᴤ꞉ꞌꞌͼԝᴒͼᴡᴟԜ꞉ꜜᴒᴑͼꜝꜜͼⱶⱨⱨϸ͟ͼꜞᴟ꞉ꜝᴟͼᴡꜝͼᴠᴐᴟᴒᴒꜜ꞉ꜜⱲͼᴠᴢԝ꞊ᴒᴐᴡᴠͼԜᴡͼᴡⱳᴒ꞉ᴟͼᴠ꞉ᴡᴒ᷅
Ⱬᴢᴟ꞉ꜜⱲͼᴠᴐᴟᴒᴒꜜ꞉ꜜⱲԓͼᴠ꞉ᴡᴒͼꜞᴒᴟᴠꜝꜜꜜᴒꞌͼᴤ꞉ꞌꞌͼᴡᴟԜ꞉ꜜᴠᴢԝ꞊ᴒᴐᴡᴠͼԜꜜᴑͼᴐԜᴟᴒⱲ꞉ᴣᴒᴟᴠͼꜝꜜͼ꞉ᴑᴒꜜᴡ꞉ⱱᴦ꞉ꜜⱲͼᴠᴦꜛꜞᴡꜝꜛᴠͼꜝⱱͼԜꜜͼ
ԜᴡᴡԜᴐꞋԓͼᴡⱳᴒͼᴟᴒꜟᴢ꞉ᴟᴒꜛᴒꜜᴡᴠͼⱱꜝᴟͼᴟᴒꜞꜝᴟᴡ꞉ꜜⱲͼԜᴡᴡԜᴐꞋᴠͼԜꜜᴑͼᴡⱳᴒͼ꞉ꜜⱱꜝᴟꜛԜᴡ꞉ꜝꜜͼᴡⱳᴒᴦͼᴤ꞉ꞌꞌͼԝᴒͼᴒᴥꜞᴒᴐᴡᴒᴑͼᴡꜝͼ
ꜞᴟꜝᴣ꞉ᴑᴒ᷅ͼᴁⱳᴒͼᴠᴢԝ꞊ᴒᴐᴡͼӿԜꜜᴑͼᴐԜᴟᴒⱲ꞉ᴣᴒᴟԐͼᴤ꞉ꞌꞌͼᴐꜝꜜⱱ꞉ᴟꜛͼᴡⱳᴒ꞉ᴟͼᴢꜜᴑᴒᴟᴠᴡԜꜜᴑ꞉ꜜⱲͼꜝⱱͼᴤⱳԜᴡͼ꞉ᴠͼᴟᴒꜟᴢ꞉ᴟᴒᴑͼꜝⱱͼᴡⱳᴒꜛͼ
ⱱꜝᴟͼᴟᴒꜞꜝᴟᴡ꞉ꜜⱲͼԜᴡᴡԜᴐꞋᴠͼᴡꜝͼᴡⱳᴒͼᴠ꞉ᴡᴒ᷅
ⱨᴡͼᴠᴐᴟᴒᴒꜜ꞉ꜜⱲԓͼᴠᴢԝ꞊ᴒᴐᴡͼⱶⱨⱬͼԜᴡᴡԜᴐꞋͼⱳ꞉ᴠᴡꜝᴟᴦͼᴤ꞉ꞌꞌͼԝᴒͼᴐꜝꞌꞌᴒᴐᴡᴒᴑ᷅ͼⱷꜜⱱꜝᴟꜛԜᴡ꞉ꜝꜜͼᴐꜝꞌꞌᴒᴐᴡᴒᴑͼᴤ꞉ꞌꞌͼ꞉ꜜᴐꞌᴢᴑᴒͼ
Ԝꜜᴦͼꜞᴟ꞉ꜝᴟͼⱳ꞉ᴠᴡꜝᴟᴦͼꜝⱱͼꞌԜᴟᴦꜜⱲᴒԜꞌͼԜᴡᴡԜᴐꞋᴠԓͼԜᴡᴡԜᴐꞋͼⱱᴟᴒꜟᴢᴒꜜᴐᴦԓͼԜᴣᴒᴟԜⱲᴒͼᴠᴒᴣᴒᴟ꞉ᴡᴦԓͼꜞᴟᴒᴑꜝꜛ꞉ꜜԜꜜᴡͼԜᴡᴡԜᴐꞋͼ
ꞌꜝᴐԜᴡ꞉ꜝꜜӿᴠԐԓͼԜᴣᴒᴟԜⱲᴒͼᴑᴢᴟԜᴡ꞉ꜝꜜԓͼԜᴐᴢᴡᴒͼԜᴡᴡԜᴐꞋͼᴡⱳᴒᴟԜꜞᴦͼᴢᴠᴒԓͼԜꜜᴑͼⱳ꞉ᴠᴡꜝᴟᴦͼꜝⱱͼꞌꜝꜜⱲ᷄ᴡᴒᴟꜛͼꜞᴟꜝꜞⱳᴦꞌԜᴥ꞉ᴠ᷅
Ⱬᴢᴟ꞉ꜜⱲͼᴡⱳᴒͼᴠᴡᴢᴑᴦԓͼᴠᴢԝ꞊ᴒᴐᴡᴠͼӿꜝᴟͼᴐԜᴟᴒⱲ꞉ᴣᴒᴟᴠԓͼ꞉ꜜͼᴡⱳᴒͼᴒᴣᴒꜜᴡͼᴡⱳᴒͼᴠᴢԝ꞊ᴒᴐᴡͼ꞉ᴠͼⱣͼ᷈˲ͼᴦᴒԜᴟᴠͼꜝꞌᴑԐͼᴤ꞉ꞌꞌͼԝᴒͼ
꞉ꜜᴠᴡᴟᴢᴐᴡᴒᴑͼᴡꜝͼꜜꜝᴡ꞉ⱱᴦͼԜꜜᴑͼᴟᴒꜞꜝᴟᴡͼᴑᴒᴡԜ꞉ꞌᴠͼᴡꜝͼᴡⱳᴒͼᴠᴡᴢᴑᴦͼᴠ꞉ᴡᴒͼᴤ꞉ᴡⱳ꞉ꜜͼⅎ᷉ͼⱳꜝᴢᴟᴠͼꜝⱱͼᴡⱳᴒͼꜝꜜᴠᴒᴡͼꜝⱱͼԜꜜͼⱶⱨⱬͼ
ԜᴡᴡԜᴐꞋ᷅ͼⱷꜜͼᴡⱳᴒͼᴒᴣᴒꜜᴡͼᴡⱳԜᴡͼԜͼᴠᴢԝ꞊ᴒᴐᴡͼ꞉ᴠͼ꞉ꜜᴐԜꜞԜᴐ꞉ᴡԜᴡᴒᴑͼⱱꜝꞌꞌꜝᴤ꞉ꜜⱲͼԜꜜͼԜᴡᴡԜᴐꞋԓͼᴡⱳ꞉ᴠͼ꞉ꜜⱱꜝᴟꜛԜᴡ꞉ꜝꜜͼᴐԜꜜͼԝᴒͼ
ꜞᴟꜝᴣ꞉ᴑᴒᴑͼᴡꜝͼᴡⱳᴒͼᴠ꞉ᴡᴒͼԝᴦͼԜͼⱱԜꜛ꞉ꞌᴦͼꜛᴒꜛԝᴒᴟͼꜝᴟͼꜝᴡⱳᴒᴟͼ꞉ꜜᴑ꞉ᴣ꞉ᴑᴢԜꞌͼᴤ꞉ᴡⱳͼᴑᴒᴡԜ꞉ꞌᴒᴑͼꞋꜜꜝᴤꞌᴒᴑⱲᴒͼꜝⱱͼᴡⱳᴒͼ
ᴒᴣᴒꜜᴡ᷅ͼⱷⱱͼᴑᴒᴠ꞉ᴟᴒᴑͼԝᴦͼᴡⱳᴒͼᴠᴢԝ꞊ᴒᴐᴡԓͼꜛᴒꜛꜝᴟᴦͼԜ꞉ᴑᴠͼꜛԜᴦͼԝᴒͼꜞᴟꜝᴣ꞉ᴑᴒᴑͼᴡꜝͼԜᴠᴠ꞉ᴠᴡͼ꞉ꜜͼᴡᴟԜᴐꞋ꞉ꜜⱲͼԜꜜᴦͼⱶⱨⱬͼ
ԜᴡᴡԜᴐꞋᴠͼᴠᴢԝ꞊ᴒᴐᴡᴠͼᴒᴥꜞᴒᴟ꞉ᴒꜜᴐᴒ᷅ͼᴄᴒᴒꞋꞌᴦͼᴐꜝꜛꜛᴢꜜ꞉ᴐԜᴡ꞉ꜝꜜͼԝᴒᴡᴤᴒᴒꜜͼᴡⱳᴒͼꜞԜᴡ꞉ᴒꜜᴡᴠͼԜꜜᴑͼᴡⱳᴒͼᴠ꞉ᴡᴒԓͼ꞉ꜜᴐꞌᴢᴑ꞉ꜜⱲͼ
ᴟᴒꜞꜝᴟᴡᴠͼꜝⱱͼⱶⱨⱬͼԜᴡᴡԜᴐꞋᴠԓͼꜛᴢᴠᴡͼԝᴒͼᴑꜝᴐᴢꜛᴒꜜᴡᴒᴑͼ꞉ꜜͼᴡⱳᴒͼᴒⱪϸⱴ᷅
ᴀᴢԝ꞊ᴒᴐᴡᴠͼӿꜝᴟͼᴐԜᴟᴒⱲ꞉ᴣᴒᴟᴠԐͼᴤ꞉ꞌꞌͼԝᴒͼԜᴠꞋᴒᴑͼᴡꜝͼꜞᴟꜝᴣ꞉ᴑᴒͼᴡⱳᴒͼⱱꜝꞌꞌꜝᴤ꞉ꜜⱲͼ꞉ꜜⱱꜝᴟꜛԜᴡ꞉ꜝꜜͼᴤⱳᴒꜜͼᴟᴒꜞꜝᴟᴡ꞉ꜜⱲͼԜꜜͼ
ԜᴡᴡԜᴐꞋⱡ
ᶄ
ⱫԜᴡᴒͼԜꜜᴑͼᴡ꞉ꜛᴒͼᴠᴦꜛꜞᴡꜝꜛᴠͼꜝⱱͼԜꜜͼԜᴡᴡԜᴐꞋͼᴤᴒᴟᴒͼⱱ꞉ᴟᴠᴡͼᴒᴥꜞᴒᴟ꞉ᴒꜜᴐᴒᴑ
ᶄ
Ⱬᴒᴠᴐᴟ꞉ꜞᴡ꞉ꜝꜜͼꜝⱱͼᴠᴦꜛꜞᴡꜝꜛᴠͼᴒᴥꜞᴒᴟ꞉ᴒꜜᴐᴒᴑԓͼ꞉ꜜᴐꞌᴢᴑ꞉ꜜⱲͼꞌꜝᴐԜᴡ꞉ꜝꜜӿᴠԐ
ᶄ
ⱷꜛꜞԜᴐᴡͼꜝꜜͼԜᴐᴡ꞉ᴣ꞉ᴡᴦͼԜꜜᴑͼᴤⱳᴒᴡⱳᴒᴟͼԜꜜᴦͼԜᴠᴠ꞉ᴠᴡԜꜜᴐᴒͼꜝᴟͼꜛᴒᴑ꞉ᴐԜꞌͼ꞉ꜜᴡᴒᴟᴣᴒꜜᴡ꞉ꜝꜜͼᴤԜᴠͼᴟᴒꜟᴢ꞉ᴟᴒᴑԓͼ
꞉ꜜᴐꞌᴢᴑ꞉ꜜⱲͼⱳꜝᴠꜞ꞉ᴡԜꞌ꞉ᴧԜᴡ꞉ꜝꜜᴠͼꜝᴟͼᴒꜛᴒᴟⱲᴒꜜᴐᴦͼᴑᴒꜞԜᴟᴡꜛᴒꜜᴡͼᴣ꞉ᴠ꞉ᴡᴠ
ᶄ
ⱨꜜᴦͼꜛᴒᴑ꞉ᴐԜᴡ꞉ꜝꜜᴠͼᴢᴠᴒᴑͼᴡꜝͼᴡᴟᴒԜᴡͼᴡⱳᴒͼԜᴡᴡԜᴐꞋ
ᶄ
ⱷⱱͼᴡⱳᴒͼԜᴡᴡԜᴐꞋͼᴟᴒᴠꜝꞌᴣᴒᴑԓͼᴑԜᴡᴒͼԜꜜᴑͼᴡ꞉ꜛᴒͼᴡⱳᴒͼᴠᴢԝ꞊ᴒᴐᴡͼᴤԜᴠͼꜜꜝͼꞌꜝꜜⱲᴒᴟͼᴒᴥꜞᴒᴟ꞉ᴒꜜᴐ꞉ꜜⱲͼᴠᴦꜛꜞᴡꜝꜛᴠ

Ⱬᴅ᷄᷉Ⱡ᷊᷇
ⱪꞌ꞉ꜜ꞉ᴐԜꞌͼᴁᴟ꞉Ԝꞌͼ͟ᴟꜝᴡꜝᴐꜝꞌⱡͼⱫᴅ᷄᷉Ⱡ᷊᷊᷇᷄᷇
ⱨꜛᴒꜜᴑꜛᴒꜜᴡͼ᷊᷅᷇ͼⱴ꞉ꜜԜꞌⱡͼ᷇ⱠͼꜗԜꜜᴢԜᴟᴦ᷉᷇᷈ⅎ
ⱪꜝꜜⱱ꞉ᴑᴒꜜᴡ꞉Ԝꞌ
͟ԜⱲᴒͼ᷿᷈
ⱫᴦԜᴥͼⱪꜝᴟꜞ᷅
ᴀ꞉ᴡᴒͼꜞᴒᴟᴠꜝꜜꜜᴒꞌͼᴤ꞉ꞌꞌͼᴟᴒᴣ꞉ᴒᴤͼᴡⱳᴒͼ꞉ꜜⱱꜝᴟꜛԜᴡ꞉ꜝꜜͼꜞᴟꜝᴣ꞉ᴑᴒᴑͼԜꜜᴑͼᴠꜝꞌ꞉ᴐ꞉ᴡͼԜᴑᴑ꞉ᴡ꞉ꜝꜜԜꞌͼ꞉ꜜⱱꜝᴟꜛԜᴡ꞉ꜝꜜͼԜᴠͼ
ꜜᴒᴐᴒᴠᴠԜᴟᴦͼᴡꜝͼᴑꜝᴐᴢꜛᴒꜜᴡͼᴡⱳᴒͼԜᴡᴡԜᴐꞋԓͼԜᴠͼᴑᴒᴠᴐᴟ꞉ԝᴒᴑͼ꞉ꜜͼⱶⱨⱨϸ᷅͟ͼ
ᴀᴢԝ꞊ᴒᴐᴡᴠͼᴤԜᴠⱳ꞉ꜜⱲͼꜝᴢᴡͼꜝⱱͼꜙᴁ͟ͼᴤ꞉ꞌꞌͼԝᴒͼᴐꜝꜜᴡԜᴐᴡᴒᴑͼԝᴦͼᴡⱳᴒͼᴠ꞉ᴡᴒͼԜᴡͼᴡⱳᴒͼᴒꜜᴑͼꜝⱱͼᴡⱳᴒͼ᷉ͼᴤᴒᴒꞋͼᴤԜᴠⱳꜝᴢᴡͼ
ꜞᴒᴟ꞉ꜝᴑ᷅ͼᴁⱳᴒͼⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟͼꜛᴢᴠᴡͼᴐꜝꜜⱱ꞉ᴟꜛͼᴡⱳᴒͼᴠᴢԝ꞊ᴒᴐᴡͼⱳԜᴠͼᴠᴢᴐᴐᴒᴠᴠⱱᴢꞌꞌᴦͼᴐꜝꜛꜞꞌᴒᴡᴒᴑͼᴡⱳᴒͼ᷉ͼᴤᴒᴒꞋͼ
ᴤԜᴠⱳꜝᴢᴡͼꜞᴒᴟ꞉ꜝᴑͼԝᴒⱱꜝᴟᴒͼᴡⱳᴒᴦͼᴐԜꜜͼᴒꜜᴡᴒᴟͼᴡⱳᴒͼᴟᴢꜜ᷄꞉ꜜͼꜞᴒᴟ꞉ꜝᴑ᷅ͼⱪꜝꜜⱱ꞉ᴟꜛԜᴡ꞉ꜝꜜͼꜝⱱͼᴤԜᴠⱳꜝᴢᴡͼᴤ꞉ꞌꞌͼԝᴒͼ
ᴐԜꜞᴡᴢᴟᴒᴑͼ꞉ꜜͼᴡⱳᴒͼᴒⱪϸⱴ᷅ͼ
ᴀ꞉ᴡᴒͼꜞᴒᴟᴠꜝꜜꜜᴒꞌͼᴤ꞉ꞌꞌͼᴐꜝꜜᴡԜᴐᴡͼᴡⱳᴒͼᴠᴢԝ꞊ᴒᴐᴡͼꜝᴟͼᴐԜᴟᴒⱲ꞉ᴣᴒᴟͼᴤᴒᴒꞋꞌᴦԓͼꜝᴟͼԜꜞꜞᴟꜝᴥ꞉ꜛԜᴡᴒꞌᴦͼⅎͼᴑԜᴦᴠͼԜⱱᴡᴒᴟͼᴡⱳᴒ꞉ᴟͼ
ꞌԜᴠᴡͼᴐꜝꜜᴡԜᴐᴡͼᴤ꞉ᴡⱳͼᴡⱳᴒͼᴠᴢԝ꞊ᴒᴐᴡԓͼᴡⱳᴟꜝᴢⱲⱳꜝᴢᴡͼᴡⱳᴒͼᴟᴢꜜ᷄꞉ꜜͼꜞᴒᴟ꞉ꜝᴑ᷅ͼⱷⱱͼᴡⱳᴒͼᴠᴢԝ꞊ᴒᴐᴡͼᴒᴥꜞᴒᴟ꞉ᴒꜜᴐᴒᴠͼ᷈ꜝᴟͼꜛꜝᴟᴒͼ
ⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟ᷄ᴐꜝꜜⱱ꞉ᴟꜛᴒᴑͼⱶⱨⱬͼԜᴡᴡԜᴐꞋᴠͼԝᴦͼᴡⱳᴒͼᴒꜜᴑͼꜝⱱͼᴤᴒᴒꞋͼ᷾ԓͼᴡⱳᴒͼᴠᴢԝ꞊ᴒᴐᴡͼᴤ꞉ꞌꞌͼⱳԜᴣᴒͼⱱᴢꞌⱱ꞉ꞌꞌᴒᴑͼᴡⱳᴒͼᴟᴢꜜ᷄
꞉ꜜͼᴟᴒꜟᴢ꞉ᴟᴒꜛᴒꜜᴡͼԜꜜᴑͼꜛԜᴦͼꜞᴟꜝᴐᴒᴒᴑͼᴡꜝͼᴒꜜᴟꜝꞌꞌꜛᴒꜜᴡͼԜꜜᴑͼᴟԜꜜᴑꜝꜛ꞉ᴧԜᴡ꞉ꜝꜜ᷅ͼᴀᴢԝ꞊ᴒᴐᴡᴠͼᴤⱳꜝͼᴒᴥꜞᴒᴟ꞉ᴒꜜᴐᴒͼ᷊ͼꜝᴟͼ
ꜛꜝᴟᴒͼⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟ᷄ᴐꜝꜜⱱ꞉ᴟꜛᴒᴑͼԜᴡᴡԜᴐꞋᴠͼᴐԜꜜͼᴒᴥ꞉ᴡͼᴡⱳᴒͼᴟᴢꜜ᷄꞉ꜜͼꜞᴒᴟ꞉ꜝᴑͼᴒԜᴟꞌᴦͼԜꜜᴑͼꜞᴟꜝᴐᴒᴒᴑͼᴡꜝͼᴒꜜᴟꜝꞌꞌꜛᴒꜜᴡͼ
ԜꜜᴑͼᴟԜꜜᴑꜝꜛ꞉ᴧԜᴡ꞉ꜝꜜ᷅ͼⱷⱱͼᴡⱳᴒͼᴠᴢԝ꞊ᴒᴐᴡͼᴒᴥꜞᴒᴟ꞉ᴒꜜᴐᴒᴠͼꜜꜝͼⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟ᷄ᴐꜝꜜⱱ꞉ᴟꜛᴒᴑͼⱶⱨⱬͼԜᴡᴡԜᴐꞋᴠͼᴡⱳᴒͼᴒꜜᴑͼꜝⱱͼ
ᴡⱳᴒͼᴠᴢԝ꞊ᴒᴐᴡᴤ꞉ꞌꞌͼᴟᴒꜛԜ꞉ꜜͼ꞉ꜜͼᴡⱳᴒͼᴟᴢꜜ᷄꞉ꜜͼꜞᴒᴟ꞉ꜝᴑͼⱱꜝᴟͼԜꜜͼԜᴑᴑ꞉ᴡ꞉ꜝꜜԜꞌͼ᷾ᴤᴒᴒꞋᴠ᷅ͼᴁⱳᴒͼꜛԜᴥ꞉ꜛᴢꜛͼᴑᴢᴟԜᴡ꞉ꜝꜜͼꜝⱱͼ
ᴡⱳᴒͼᴟᴢꜜ᷄꞉ꜜͼꜞᴒᴟ꞉ꜝᴑͼ꞉ᴠͼ˲ͼᴤᴒᴒꞋᴠ᷅ⱷⱱͼᴟᴢꜜ᷄꞉ꜜͼⱳԜᴠͼԝᴒᴒꜜͼᴒᴥᴡᴒꜜᴑᴒᴑͼԜꜜᴑͼᴡⱳᴒͼᴠᴢԝ꞊ᴒᴐᴡͼⱳԜᴠͼ᷉ͼꜝᴟͼꜛꜝᴟᴒͼ
ⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟ᷄ᴐꜝꜜⱱ꞉ᴟꜛᴒᴑͼⱶⱨⱬͼԜᴡᴡԜᴐꞋᴠͼԝᴦͼᴡⱳᴒͼᴒꜜᴑͼꜝⱱͼᴤᴒᴒꞋͼ˲ԓͼᴡⱳᴒͼᴠᴢԝ꞊ᴒᴐᴡͼᴤ꞉ꞌꞌͼⱳԜᴣᴒͼⱱᴢꞌⱱ꞉ꞌꞌᴒᴑͼᴡⱳᴒͼᴟᴢꜜ᷄
꞉ꜜͼᴟᴒꜟᴢ꞉ᴟᴒꜛᴒꜜᴡͼԜꜜᴑͼꜛԜᴦͼꜞᴟꜝᴐᴒᴒᴑͼᴡꜝͼᴡⱳᴒͼᴑꜝᴢԝꞌᴒ᷄ԝꞌ꞉ꜜᴑͼᴡᴟᴒԜᴡꜛᴒꜜᴡͼꜞᴒᴟ꞉ꜝᴑ᷅ͼᴁꜝͼԝᴒͼᴒꞌ꞉Ⱳ꞉ԝꞌᴒͼⱱꜝᴟͼ
ᴒꜜᴟꜝꞌꞌꜛᴒꜜᴡԓͼᴠᴢԝ꞊ᴒᴐᴡᴠͼᴤⱳꜝͼⱳԜᴣᴒͼᴡⱳᴒ꞉ᴟͼᴟᴢꜜ᷄꞉ꜜͼᴒᴥᴡᴒꜜᴑᴒᴑͼꜛᴢᴠᴡͼᴐꜝꜛꜞꞌᴒᴡᴒͼᴡⱳᴒͼⱱᴢꞌꞌͼ˲᷄ᴤᴒᴒꞋͼᴟᴢꜜ᷄꞉ꜜͼꜞᴒᴟ꞉ꜝᴑͼ
ꜞᴟ꞉ꜝᴟͼᴡꜝͼᴒꜜᴡᴒᴟ꞉ꜜⱲͼᴡⱳᴒͼᴡᴟᴒԜᴡꜛᴒꜜᴡͼꜞᴒᴟ꞉ꜝᴑ᷅ͼᴀᴢԝ꞊ᴒᴐᴡᴠͼᴤⱳꜝͼᴑꜝͼꜜꜝᴡͼꜛᴒᴒᴡͼᴡⱳᴒͼꜛ꞉ꜜ꞉ꜛᴢꜛͼԜᴡᴡԜᴐꞋͼᴟԜᴡᴒͼᴑᴢᴟ꞉ꜜⱲͼ
ᴟᴢꜜ᷄꞉ꜜͼᴤ꞉ꞌꞌͼԝᴒͼᴐꜝꜜᴠ꞉ᴑᴒᴟᴒᴑͼԜͼᴠᴐᴟᴒᴒꜜͼⱱԜ꞉ꞌ᷅
Ⱬᴢᴟ꞉ꜜⱲͼᴡⱳᴒͼᴡᴟᴒԜᴡꜛᴒꜜᴡͼꜞᴒᴟ꞉ꜝᴑͼᴠ꞉ᴡᴒͼꜞᴒᴟᴠꜝꜜꜜᴒꞌͼᴤ꞉ꞌꞌͼᴐꜝꜜᴡԜᴐᴡͼᴡⱳᴒͼᴠᴢԝ꞊ᴒᴐᴡͼꜝᴟͼᴐԜᴟᴒⱲ꞉ᴣᴒᴟͼꜝꜜᴐᴒͼԝᴒᴡᴤᴒᴒꜜͼ
ᴠᴐⱳᴒᴑᴢꞌᴒᴑͼᴠᴡᴢᴑᴦͼᴣ꞉ᴠ꞉ᴡᴠͼꜝᴟͼԜꜞꜞᴟꜝᴥ꞉ꜛԜᴡᴒꞌᴦͼⅎͼᴑԜᴦᴠͼԜⱱᴡᴒᴟͼᴡⱳᴒ꞉ᴟͼꞌԜᴠᴡͼᴐꜝꜜᴡԜᴐᴡͼᴡꜝͼᴠꜝꞌ꞉ᴐ꞉ᴡͼⱱꜝᴟͼԜꜜᴦͼⱶⱨⱬͼ
ԜᴡᴡԜᴐꞋͼ꞉ꜜⱱꜝᴟꜛԜᴡ꞉ꜝꜜͼꜜꜝᴡͼԜꞌᴟᴒԜᴑᴦͼᴟᴒꜞꜝᴟᴡᴒᴑ᷅
ᴁⱳᴟꜝᴢⱲⱳꜝᴢᴡͼᴡⱳᴒͼᴑᴢᴟԜᴡ꞉ꜝꜜͼꜝⱱͼᴡⱳᴒͼᴑꜝᴢԝꞌᴒ᷄ԝꞌ꞉ꜜᴑͼᴠᴡᴢᴑᴦԓͼᴑᴢᴟ꞉ꜜⱲͼᴒԜᴐⱳͼᴠᴡᴢᴑᴦͼᴣ꞉ᴠ꞉ᴡͼԜᴡͼᴡⱳᴒͼ꞉ꜜᴣᴒᴠᴡ꞉ⱲԜᴡ꞉ᴣᴒͼ
ᴠ꞉ᴡᴒԓͼᴠ꞉ᴡᴒͼꜞᴒᴟᴠꜝꜜꜜᴒꞌͼᴤ꞉ꞌꞌͼᴠꜝꞌ꞉ᴐ꞉ᴡͼⱱꜝᴟͼԜꜜᴦͼꜜᴒᴤͼⱶⱨⱬͼԜᴡᴡԜᴐꞋͼ꞉ꜜⱱꜝᴟꜛԜᴡ꞉ꜝꜜͼᴡⱳԜᴡͼᴤԜᴠͼꜜꜝᴡͼԜꞌᴟᴒԜᴑᴦͼꜞᴟꜝᴣ꞉ᴑᴒᴑͼ
ᴡꜝͼᴡⱳᴒͼᴠ꞉ᴡᴒ᷅
ⱷꜜͼᴡⱳ꞉ᴠͼᴠᴡᴢᴑᴦͼⱶⱨⱬͼԜᴡᴡԜᴐꞋᴠͼᴤ꞉ꞌꞌͼԝᴒͼᴐԜꜞᴡᴢᴟᴒᴑͼԜᴠͼⱨⱬᴠ᷅ͼⱨꞌꞌͼⱨⱬᴠԓͼᴟᴒⱲԜᴟᴑꞌᴒᴠᴠͼꜝⱱͼᴠᴒᴟ꞉ꜝᴢᴠꜜᴒᴠᴠԓͼᴠᴒᴣᴒᴟ꞉ᴡᴦԓͼ
ꜝᴟͼᴐԜᴢᴠԜꞌͼᴟᴒꞌԜᴡ꞉ꜝꜜᴠⱳ꞉ꜞͼᴡꜝͼᴠᴡᴢᴑᴦͼᴑᴟᴢⱲԓͼᴤ꞉ꞌꞌͼԝᴒͼᴟᴒᴐꜝᴟᴑᴒᴑͼꜝꜜͼᴡⱳᴒͼⱨⱬͼꜞԜⱲᴒͼꜝⱱͼᴡⱳᴒͼᴒⱪϸⱴ᷅ͼⱨꜜᴦͼⱨⱬͼ
ᴟᴒꜞꜝᴟᴡᴒᴑͼᴡꜝͼᴡⱳᴒͼᴠ꞉ᴡᴒͼꜛᴒᴒᴡ꞉ꜜⱲͼᴐᴟ꞉ᴡᴒᴟ꞉ԜͼⱱꜝᴟͼԜͼᴠᴒᴟ꞉ꜝᴢᴠͼԜᴑᴣᴒᴟᴠᴒͼᴒᴣᴒꜜᴡͼꜛᴢᴠᴡͼԝᴒͼᴟᴒꜞꜝᴟᴡᴒᴑͼᴡꜝͼᴡⱳᴒͼᴀꜞꜝꜜᴠꜝᴟͼ
ᴢᴠ꞉ꜜⱲͼᴡⱳᴒͼᴀⱨⱬͼϸᴒꜞꜝᴟᴡ꞉ꜜⱲͼⱴꜝᴟꜛͼ꞉ꜜͼᴡⱳᴒͼⱬⱫⱪͼᴠᴦᴠᴡᴒꜛᴤ꞉ᴡⱳ꞉ꜜͼ᷉᷾ͼⱳꜝᴢᴟᴠꜝⱱͼԝᴒᴐꜝꜛ꞉ꜜⱲͼԜᴤԜᴟᴒͼꜝⱱͼᴡⱳᴒͼ
ᴒᴣᴒꜜᴡ᷅ͼⱴꜝᴟͼԜꞌꞌͼᴠᴒᴟ꞉ꜝᴢᴠͼԜᴑᴣᴒᴟᴠᴒͼᴒᴣᴒꜜᴡᴠͼᴡⱳԜᴡͼԜᴟᴒͼᴟᴒꜞꜝᴟᴡᴒᴑͼԜᴠͼⱶⱨⱬͼԜᴡᴡԜᴐꞋᴠԓͼᴡⱳᴒͼ͟ᴟ꞉ꜜᴐ꞉ꜞԜꞌͼⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟͼ
ꜝᴟͼꜞⱳᴦᴠ꞉ᴐ꞉Ԝꜜͼᴑᴒᴠ꞉Ⱳꜜᴒᴒͼᴤ꞉ꞌꞌͼᴟᴒᴣ꞉ᴒᴤͼᴡⱳᴒͼᴒᴣᴒꜜᴡͼᴤ꞉ᴡⱳ꞉ꜜͼ᷉᷾ͼⱳꜝᴢᴟᴠͼꜝⱱͼ꞉ꜜ꞉ᴡ꞉Ԝꞌͼꜜꜝᴡ꞉ⱱ꞉ᴐԜᴡ꞉ꜝꜜͼԜꜜᴑԓͼ꞉ꜜͼ
ԜᴐᴐꜝᴟᴑԜꜜᴐᴒͼᴤ꞉ᴡⱳͼⱶⱨⱨϸ͟ԓͼᴒᴣԜꞌᴢԜᴡᴒͼ꞉ⱱͼ꞉ᴡͼᴟᴒꜞᴟᴒᴠᴒꜜᴡᴒᴑͼԜͼᴐꜝꜜⱱ꞉ᴟꜛᴒᴑͼⱶⱨⱬͼԜᴡᴡԜᴐꞋ᷅ͼⱴꜝᴟͼԜꞌꞌͼꜜꜝꜜ᷄ᴠᴒᴟ꞉ꜝᴢᴠͼ
ⱨⱬᴠͼᴡⱳԜᴡͼԜᴟᴒͼᴟᴒꜞꜝᴟᴡᴒᴑͼԜᴠͼⱶⱨⱬͼԜᴡᴡԜᴐꞋᴠԓͼᴡⱳᴒͼ͟ᴟ꞉ꜜᴐ꞉ꜞԜꞌͼⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟͼꜝᴟͼꜞⱳᴦᴠ꞉ᴐ꞉Ԝꜜͼᴑᴒᴠ꞉Ⱳꜜᴒᴒͼᴤ꞉ꞌꞌͼ
ᴟᴒᴣ꞉ᴒᴤͼᴡⱳᴒͼᴒᴣᴒꜜᴡͼᴤ꞉ᴡⱳ꞉ꜜͼ᷊ͼᴑԜᴦᴠͼꜝⱱͼ꞉ꜜ꞉ᴡ꞉Ԝꞌͼꜜꜝᴡ꞉ⱱ꞉ᴐԜᴡ꞉ꜝꜜͼԜꜜᴑԓͼ꞉ꜜͼԜᴐᴐꜝᴟᴑԜꜜᴐᴒͼᴤ꞉ᴡⱳͼⱶⱨⱨϸ͟ԓͼᴒᴣԜꞌᴢԜᴡᴒͼ꞉ⱱͼ
꞉ᴡͼᴟᴒꜞᴟᴒᴠᴒꜜᴡᴒᴑͼԜͼᴐꜝꜜⱱ꞉ᴟꜛᴒᴑͼⱶⱨⱬͼԜᴡᴡԜᴐꞋ᷅ͼⱷⱱͼꜜᴒᴐᴒᴠᴠԜᴟᴦͼⱱꜝᴟͼᴡⱳᴒͼᴒᴣԜꞌᴢԜᴡ꞉ꜝꜜԓͼᴡⱳᴒͼⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟͼꜝᴟͼ
ᴑᴒᴠ꞉ⱲꜜᴒᴒͼꜛԜᴦͼᴐꜝꜜᴡԜᴐᴡͼᴡⱳᴒͼᴠᴢԝ꞊ᴒᴐᴡͼⱱꜝᴟͼԜᴑᴑ꞉ᴡ꞉ꜝꜜԜꞌͼ꞉ꜜⱱꜝᴟꜛԜᴡ꞉ꜝꜜ᷅ͼⱨꜜᴦͼᴠᴢԝ꞊ᴒᴐᴡ᷄ᴟᴒꜞꜝᴟᴡᴒᴑͼԜᴡᴡԜᴐꞋͼꜜꜝᴡͼ
ᴐꜝꜜⱱ꞉ᴟꜛᴒᴑͼԝᴦͼᴡⱳᴒͼⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟͼꜛᴢᴠᴡͼⱳԜᴣᴒͼԜꜜͼԜꞌᴡᴒᴟꜜԜᴡᴒͼⱨⱬͼᴑ꞉ԜⱲꜜꜝᴠ꞉ᴠͼᴟᴒᴐꜝᴟᴑᴒᴑ᷅ͼⱨꞌꞌͼᴠᴢԝ꞊ᴒᴐᴡ᷄ᴟᴒꜞꜝᴟᴡᴒᴑͼ
Ԝꜜᴑͼⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟ᷄ᴐꜝꜜⱱ꞉ᴟꜛᴒᴑͼⱶⱨⱬͼԜᴡᴡԜᴐꞋᴠͼᴤ꞉ꞌꞌͼԝᴒͼᴟᴒᴐꜝᴟᴑᴒᴑͼ꞉ꜜͼᴡⱳᴒͼᴒⱪϸⱴ᷅
ⱬꜛᴒᴟⱲᴒꜜᴐᴦͼᴑᴒꜞԜᴟᴡꜛᴒꜜᴡͼᴣ꞉ᴠ꞉ᴡᴠͼⱱꜝᴟͼⱶⱨⱬͼԜᴡᴡԜᴐꞋᴠͼԜꜜᴑͼⱶⱨⱬͼԜᴡᴡԜᴐꞋᴠͼᴟᴒᴠᴢꞌᴡ꞉ꜜⱲͼ꞉ꜜͼⱳꜝᴠꜞ꞉ᴡԜꞌͼԜᴑꜛ꞉ᴠᴠ꞉ꜝꜜᴠͼ
ᴤ꞉ꞌꞌͼԝᴒͼᴐԜꜞᴡᴢᴟᴒᴑ᷅

Ⱬᴅ᷄᷉Ⱡ᷊᷇
ⱪꞌ꞉ꜜ꞉ᴐԜꞌͼᴁᴟ꞉Ԝꞌͼ͟ᴟꜝᴡꜝᴐꜝꞌⱡͼⱫᴅ᷄᷉Ⱡ᷊᷊᷇᷄᷇
ⱨꜛᴒꜜᴑꜛᴒꜜᴡͼ᷊᷅᷇ͼⱴ꞉ꜜԜꞌⱡͼ᷇ⱠͼꜗԜꜜᴢԜᴟᴦ᷉᷇᷈ⅎ
ⱪꜝꜜⱱ꞉ᴑᴒꜜᴡ꞉Ԝꞌ
͟ԜⱲᴒͼ᷿᷉
ⱫᴦԜᴥͼⱪꜝᴟꜞ᷅
ᴁꜝͼԝᴒͼᴐꜝꜜⱱ꞉ᴟꜛᴒᴑͼԜᴠͼԜꜜͼⱶⱨⱬͼԜᴡᴡԜᴐꞋԓͼᴡⱳᴒͼᴒᴣᴒꜜᴡͼꜛᴢᴠᴡͼⱳԜᴣᴒͼᴠᴦꜛꜞᴡꜝꜛᴠͼꜝᴟͼᴠ꞉Ⱳꜜᴠͼᴐꜝꜜᴠ꞉ᴠᴡᴒꜜᴡͼᴤ꞉ᴡⱳͼԜꜜͼ
ԜᴡᴡԜᴐꞋͼ꞉ꜜͼԜᴡͼꞌᴒԜᴠᴡͼꜝꜜᴒͼꜝⱱͼᴡⱳᴒͼⱱꜝꞌꞌꜝᴤ꞉ꜜⱲͼꞌꜝᴐԜᴡ꞉ꜝꜜᴠⱡͼ
ᶄ
͟ᴒᴟ꞉ꜞⱳᴒᴟԜꞌͼԜꜜⱲ꞉ꜝᴒᴑᴒꜛԜⱡͼᴐᴢᴡԜꜜᴒꜝᴢᴠͼᴠᴤᴒꞌꞌ꞉ꜜⱲͼ꞉ꜜᴣꜝꞌᴣ꞉ꜜⱲͼԜꜜͼᴒᴥᴡᴟᴒꜛ꞉ᴡᴦԓͼᴡⱳᴒͼⱱԜᴐᴒԓͼꜜᴒᴐꞋԓͼᴡꜝᴟᴠꜝԓͼ
Ԝꜜᴑ᷆ꜝᴟͼⱲᴒꜜ꞉ᴡꜝᴢᴟ꞉ꜜԜᴟᴦͼᴟᴒⱲ꞉ꜝꜜ᷅
ᶄ
ⱨԝᴑꜝꜛ꞉ꜜԜꞌͼԜꜜⱲ꞉ꜝᴒᴑᴒꜛԜⱡͼԜԝᴑꜝꜛ꞉ꜜԜꞌͼꜞԜ꞉ꜜԓͼᴤ꞉ᴡⱳͼꜝᴟͼᴤ꞉ᴡⱳꜝᴢᴡͼԜԝᴑꜝꜛ꞉ꜜԜꞌͼᴑ꞉ᴠᴡᴒꜜᴡ꞉ꜝꜜԓͼꜜԜᴢᴠᴒԜԓͼ
ᴣꜝꜛ꞉ᴡ꞉ꜜⱲԓͼꜝᴟͼᴑ꞉ԜᴟᴟⱳᴒԜ᷅
ᶄ
ꜙԜᴟᴦꜜⱲᴒԜꞌͼԜꜜⱲ꞉ꜝᴒᴑᴒꜛԜⱡͼᴠᴡᴟ꞉ᴑꜝᴟԓͼᴑᴦᴠꜞꜜᴒԜԓͼᴑ꞉ⱱⱱ꞉ᴐᴢꞌᴡᴦͼᴠꜞᴒԜꞋ꞉ꜜⱲԓͼᴑ꞉ⱱⱱ꞉ᴐᴢꞌᴡᴦͼᴠᴤԜꞌꞌꜝᴤ꞉ꜜⱲԓͼᴡⱳᴟꜝԜᴡͼ
ᴡ꞉Ⱳⱳᴡᴒꜜ꞉ꜜⱲԓͼꜝᴟͼᴠᴤᴒꞌꞌ꞉ꜜⱲͼꜝⱱͼᴡⱳᴒͼᴡꜝꜜⱲᴢᴒԓͼꜞԜꞌԜᴡᴒԓͼᴢᴣᴢꞌԜԓͼꜝᴟͼꞌԜᴟᴦꜜᴥ᷅
Ⱬᴒᴠꜞ꞉ᴡᴒͼᴡⱳᴒͼꜞᴟᴒᴠᴒꜜᴐᴒͼꜝⱱͼᴡⱳᴒᴠᴒͼᴠᴦꜛꜞᴡꜝꜛᴠԓͼᴡⱳᴒͼⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟͼꜛԜᴦͼᴠᴡ꞉ꞌꞌͼᴐꞌ꞉ꜜ꞉ᴐԜꞌꞌᴦͼᴑᴒᴡᴒᴟꜛ꞉ꜜᴒͼᴡⱳԜᴡͼᴡⱳᴒͼ
ᴒᴣᴒꜜᴡͼᴑ꞉ᴑͼꜜꜝᴡͼᴟᴒꜞᴟᴒᴠᴒꜜᴡͼԜꜜͼⱶⱨⱬͼԜᴡᴡԜᴐꞋͼ꞉ⱱͼᴡⱳᴒᴟᴒͼԜᴟᴒͼⱱᴒԜᴡᴢᴟᴒᴠͼᴡⱳԜᴡͼᴠᴡᴟꜝꜜⱲꞌᴦͼᴟᴒⱱᴢᴡᴒͼᴠᴢᴐⱳͼԜͼᴑ꞉ԜⱲꜜꜝᴠ꞉ᴠ᷅ͼ
ⱴꜝᴟͼᴒᴥԜꜛꜞꞌᴒԓͼᴡⱳᴒͼᴟᴒꜞꜝᴟᴡᴒᴑͼᴒᴣᴒꜜᴡͼ꞉ᴠͼԜᴐᴐꜝꜛꜞԜꜜ꞉ᴒᴑͼԝᴦͼᴠᴦꜛꜞᴡꜝꜛᴠͼᴡⱳԜᴡͼԜᴟᴒͼꜜꜝᴡͼᴐꜝꜜᴠ꞉ᴠᴡᴒꜜᴡͼᴤ꞉ᴡⱳͼԜꜜͼ
ⱶⱨⱬͼԜᴡᴡԜᴐꞋͼӿᴒ᷅Ⱳ᷅ԓͼᴢᴟᴡ꞉ᴐԜᴟ꞉ԜԐԓͼᴡⱳᴒͼᴟᴒꜞꜝᴟᴡᴒᴑͼᴒᴣᴒꜜᴡͼꜞᴒᴟᴠ꞉ᴠᴡᴠͼᴤᴒꞌꞌͼԝᴒᴦꜝꜜᴑͼᴡⱳᴒͼᴡᴦꜞ꞉ᴐԜꞌͼᴡ꞉ꜛᴒͼᴐꜝᴢᴟᴠᴒͼꜝⱱͼԜꜜͼ
ⱶⱨⱬͼԜᴡᴡԜᴐꞋԓͼꜝᴟͼᴡⱳᴒᴟᴒͼ꞉ᴠͼԜͼꞌ꞉ꞋᴒꞌᴦͼԜꞌᴡᴒᴟꜜԜᴡᴒͼᴒᴡ꞉ꜝꞌꜝⱲᴦͼⱱꜝᴟͼᴡⱳᴒͼᴒᴣᴒꜜᴡͼӿᴒ᷅Ⱳ᷅ԓ ᴡⱳᴒͼᴠᴢԝ꞊ᴒᴐᴡᶳᴠͼԜԝᴑꜝꜛ꞉ꜜԜꞌͼ
ᴠᴦꜛꜞᴡꜝꜛᴠͼԜᴟᴒͼԜᴡᴡᴟ꞉ԝᴢᴡԜԝꞌᴒͼᴡꜝԜͼᴣ꞉ᴟԜꞌͼⱲԜᴠᴡᴟꜝᴒꜜᴡᴒᴟ꞉ᴡ꞉ᴠͼꜝᴢᴡԝᴟᴒԜꞋͼ꞉ꜜͼᴡⱳᴒͼⱳꜝᴢᴠᴒⱳꜝꞌᴑԐ᷅ͼ
ᴁꜝͼԝᴒͼᴐꜝᴢꜜᴡᴒᴑͼԜᴠͼԜͼᴢꜜ꞉ꜟᴢᴒͼԜᴡᴡԜᴐꞋͼᴑ꞉ᴠᴡ꞉ꜜᴐᴡͼⱱᴟꜝꜛͼᴡⱳᴒͼꜞᴟᴒᴣ꞉ꜝᴢᴠͼԜᴡᴡԜᴐꞋԓͼᴡⱳᴒͼꜜᴒᴤͼᴠᴦꜛꜞᴡꜝꜛᴠͼꜛᴢᴠᴡͼꜝᴐᴐᴢᴟͼ
ԜᴡͼꞌᴒԜᴠᴡͼ᷉᷾ͼⱳꜝᴢᴟᴠͼԜⱱᴡᴒᴟͼᴟᴒᴠꜝꞌᴢᴡ꞉ꜝꜜͼꜝⱱͼᴡⱳᴒͼꜞᴟ꞉ꜝᴟͼԜᴡᴡԜᴐꞋᶳᴠͼᴠᴦꜛꜞᴡꜝꜛᴠ᷅
6.5
Vital Signs
ᴃ꞉ᴡԜꞌͼᴠ꞉Ⱳꜜᴠͼᴤ꞉ꞌꞌͼԝᴒͼԜᴠᴠᴒᴠᴠᴒᴑͼԝᴦͼᴡⱳᴒͼⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟͼꜝᴟͼⱳ꞉ᴠ᷆ⱳᴒᴟͼꜟᴢԜꞌ꞉ⱱ꞉ᴒᴑͼᴑᴒᴠ꞉ⱲꜜᴒᴒͼԜᴐᴐꜝᴟᴑ꞉ꜜⱲͼᴡꜝͼᴡⱳᴒͼ
ᴀᴡᴢᴑᴦͼⱨᴐᴡ꞉ᴣ꞉ᴡ꞉ᴒᴠͼᴀᴐⱳᴒᴑᴢꞌᴒͼӿᴁԜԝꞌᴒͼ᷈Ԑ᷅ͼϸꜝᴢᴡ꞉ꜜᴒͼᴣ꞉ᴡԜꞌͼᴠ꞉ⱲꜜͼԜᴠᴠᴒᴠᴠꜛᴒꜜᴡᴠͼᴤ꞉ꞌꞌͼԝᴒͼᴡԜꞋᴒꜜͼᴤ꞉ᴡⱳͼᴡⱳᴒͼ
ᴠᴢԝ꞊ᴒᴐᴡͼ꞉ꜜͼᴡⱳᴒͼᴠ꞉ᴡᴡ꞉ꜜⱲͼꜝᴟͼᴠᴢꜞ꞉ꜜᴒͼꜞꜝᴠ꞉ᴡ꞉ꜝꜜͼԜⱱᴡᴒᴟͼ᷿ͼꜛ꞉ꜜᴢᴡᴒᴠͼԜᴡͼᴟᴒᴠᴡͼԜꜜᴑͼᴤ꞉ꞌꞌͼ꞉ꜜᴐꞌᴢᴑᴒͼԝꜝᴑᴦͼᴡᴒꜛꜞᴒᴟԜᴡᴢᴟᴒԓͼ
ⱳᴒԜᴟᴡͼᴟԜᴡᴒͼӿⱶϸԐԓͼԝꞌꜝꜝᴑͼꜞᴟᴒᴠᴠᴢᴟᴒͼӿⱩ͟ԐͼԜꜜᴑͼᴟᴒᴠꜞ꞉ᴟԜᴡꜝᴟᴦͼᴟԜᴡᴒͼӿϸϸԐ᷅ͼⱩ͟ͼᴠⱳꜝᴢꞌᴑͼԝᴒͼᴑᴒᴡᴒᴟꜛ꞉ꜜᴒᴑͼᴢᴠ꞉ꜜⱲͼ
ᴡⱳᴒͼᴠԜꜛᴒͼԜᴟꜛͼԜꜜᴑͼᴡⱳᴒͼᴠԜꜛᴒͼᴒꜟᴢ꞉ꜞꜛᴒꜜᴡͼⱱꜝᴟͼᴒԜᴐⱳͼԜᴠᴠᴒᴠᴠꜛᴒꜜᴡ᷅ͼᴁⱳᴒᴟᴒͼ꞉ᴠͼԜͼᶐ᷿᷈ͼꜛ꞉ꜜᴢᴡᴒͼᴤ꞉ꜜᴑꜝᴤͼⱱꜝᴟͼԜꞌꞌͼ
ᴣ꞉ᴡԜꞌͼᴠ꞉Ⱳꜜᴠ᷅
6.6
Physical Examination
ⱨͼꜞⱳᴦᴠ꞉ᴐԜꞌͼᴒᴥԜꜛ꞉ꜜԜᴡ꞉ꜝꜜͼ꞉ꜜᴐꞌᴢᴑ꞉ꜜⱲͼⱳᴒ꞉Ⱳⱳᴡԓͼᴤᴒ꞉ⱲⱳᴡͼԜꜜᴑͼᴐԜꞌᴐᴢꞌԜᴡ꞉ꜝꜜͼꜝⱱͼⱩꜝᴑᴦͼꜚԜᴠᴠͼⱷꜜᴑᴒᴥͼӿⱩꜚⱷԐͼᴤ꞉ꞌꞌͼ
ԝᴒͼꜞᴒᴟⱱꜝᴟꜛᴒᴑͼԝᴦͼᴡⱳᴒͼⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟͼꜝᴟͼⱳ꞉ᴠ᷆ⱳᴒᴟͼꜟᴢԜꞌ꞉ⱱ꞉ᴒᴑͼᴑᴒᴠ꞉ⱲꜜᴒᴒͼԜᴐᴐꜝᴟᴑ꞉ꜜⱲͼᴡꜝͼᴡⱳᴒͼᴀᴡᴢᴑᴦͼⱨᴐᴡ꞉ᴣ꞉ᴡ꞉ᴒᴠͼ
ᴀᴐⱳᴒᴑᴢꞌᴒͼӿᴁԜԝꞌᴒͼ᷈Ԑ᷅ͼᴁⱳᴒͼⱱ꞉ꜜᴑ꞉ꜜⱲᴠͼꜝⱱͼᴒԜᴐⱳͼᴒᴥԜꜛ꞉ꜜԜᴡ꞉ꜝꜜͼᴤ꞉ꞌꞌͼԝᴒͼᴟᴒᴐꜝᴟᴑᴒᴑͼꜝꜜͼᴡⱳᴒͼᴠꜝᴢᴟᴐᴒͼᴑꜝᴐᴢꜛᴒꜜᴡᴠͼ
Ԝꜜᴑͼᴒⱪϸⱴ᷅ͼᴁⱳᴒͼꜞⱳᴦᴠ꞉ᴐԜꞌͼᴒᴥԜꜛ꞉ꜜԜᴡ꞉ꜝꜜͼᴤ꞉ꞌꞌͼ꞉ꜜᴐꞌᴢᴑᴒͼᴡⱳᴒͼԝꜝᴑᴦͼᴠᴦᴠᴡᴒꜛᴠͼꞌ꞉ᴠᴡᴒᴑͼԝᴒꞌꜝᴤⱡ
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ⱶᴒ꞉ⱲⱳᴡͼԜꜜᴑͼᴤᴒ꞉ⱲⱳᴡͼӿԜᴡͼᴀᴐᴟᴒᴒꜜ꞉ꜜⱲͼᴣ꞉ᴠ꞉ᴡͼꜝꜜꞌᴦԐ
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ⱵᴒꜜᴒᴟԜꞌͼԜꜞꜞᴒԜᴟԜꜜᴐᴒ
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ⱬԜᴟᴠԓͼꜜꜝᴠᴒԓͼԜꜜᴑͼᴡⱳᴟꜝԜᴡ
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ⱶᴒԜᴑͼԜꜜᴑͼ꜠ᴒᴐꞋ
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꜡ꜞⱳᴡⱳԜꞌꜛꜝꞌꜝⱲ꞉ᴐԜꞌ

Ⱬᴅ᷄᷉Ⱡ᷊᷇
ⱪꞌ꞉ꜜ꞉ᴐԜꞌͼᴁᴟ꞉Ԝꞌͼ͟ᴟꜝᴡꜝᴐꜝꞌⱡͼⱫᴅ᷄᷉Ⱡ᷊᷊᷇᷄᷇
ⱨꜛᴒꜜᴑꜛᴒꜜᴡͼ᷊᷅᷇ͼⱴ꞉ꜜԜꞌⱡͼ᷇ⱠͼꜗԜꜜᴢԜᴟᴦ᷉᷇᷈ⅎ
ⱪꜝꜜⱱ꞉ᴑᴒꜜᴡ꞉Ԝꞌ
͟ԜⱲᴒͼ᷿᷊
ⱫᴦԜᴥͼⱪꜝᴟꜞ᷅
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ϸᴒᴠꜞ꞉ᴟԜᴡꜝᴟᴦ
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ⱪԜᴟᴑ꞉ꜝᴣԜᴠᴐᴢꞌԜᴟ
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ⱨԝᴑꜝꜛᴒꜜ
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꜠ᴒᴢᴟꜝꞌꜝⱲ꞉ᴐԜꞌ
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ⱬᴥᴡᴟᴒꜛ꞉ᴡ꞉ᴒᴠ
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ⱫᴒᴟꜛԜᴡꜝꞌꜝⱲ꞉ᴐԜꞌ
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ꜙᴦꜛꜞⱳԜᴡ꞉ᴐ
6.7
Electrocardiography (ECG)
ⱨͼᴠᴡԜꜜᴑԜᴟᴑͼ᷈᷉᷄ꞌᴒԜᴑͼⱬⱪⱵͼӿᴠ꞉ꜜⱲꞌᴒͼᴟᴒᴐꜝᴟᴑ꞉ꜜⱲԐͼᴤ꞉ꞌꞌͼԝᴒͼꜞᴒᴟⱱꜝᴟꜛᴒᴑͼԜᴐᴐꜝᴟᴑ꞉ꜜⱲͼᴡꜝͼᴡⱳᴒͼᴀᴡᴢᴑᴦͼⱨᴐᴡ꞉ᴣ꞉ᴡ꞉ᴒᴠͼ
ᴀᴐⱳᴒᴑᴢꞌᴒͼӿᴁԜԝꞌᴒͼ᷈Ԑ᷅ͼᴁⱳᴒͼᴑԜᴡᴒͼԜꜜᴑͼᴡ꞉ꜛᴒͼꜝⱱͼᴒԜᴐⱳͼⱬⱪⱵͼԜꜜᴑͼ꞉ᴡᴠͼᴟᴒᴠᴢꞌᴡᴠͼᴤ꞉ꞌꞌͼԝᴒͼᴑꜝᴐᴢꜛᴒꜜᴡᴒᴑͼ꞉ꜜͼᴡⱳᴒͼ
ᴠꜝᴢᴟᴐᴒͼᴑꜝᴐᴢꜛᴒꜜᴡᴠͼԜꜜᴑͼᴒⱪϸⱴ᷅ͼⱬꞌᴒᴐᴡᴟꜝᴐԜᴟᴑ꞉ꜝⱲᴟԜꜛᴠͼᴤ꞉ꞌꞌͼԝᴒͼᴠᴒꜜᴡͼᴡꜝͼԜͼᴐᴒꜜᴡᴟԜꞌͼᴟᴒԜᴑ꞉ꜜⱲͼᴣᴒꜜᴑꜝᴟͼⱱꜝᴟͼ
Ԝᴠᴠᴒᴠᴠꜛᴒꜜᴡ᷅
6.8
Clinical Laboratory Tests
6.8.1
Laboratory Parameters
ꜙԜԝꜝᴟԜᴡꜝᴟᴦͼᴡᴒᴠᴡ꞉ꜜⱲͼᴤ꞉ꞌꞌͼԝᴒͼꜞᴒᴟⱱꜝᴟꜛᴒᴑͼԜᴐᴐꜝᴟᴑ꞉ꜜⱲͼᴡꜝͼᴡⱳᴒͼᴀᴡᴢᴑᴦͼⱨᴐᴡ꞉ᴣ꞉ᴡ꞉ᴒᴠͼᴀᴐⱳᴒᴑᴢꞌᴒͼӿᴁԜԝꞌᴒͼ᷈Ԑ᷅
ꜙԜԝꜝᴟԜᴡꜝᴟᴦͼᴡᴒᴠᴡ꞉ꜜⱲͼ꞉ꜜᴐꞌᴢᴑᴒᴠͼⱲᴒꜜᴒᴟԜꞌͼᴠԜⱱᴒᴡᴦͼꜞԜᴟԜꜛᴒᴡᴒᴟᴠͼӿⱳᴒꜛԜᴡꜝꞌꜝⱲᴦԓͼᴐꜝԜⱲᴢꞌԜᴡ꞉ꜝꜜԓͼᴢᴟ꞉ꜜԜꞌᴦᴠ꞉ᴠԓͼԜꜜᴑͼ
ᴠᴒᴟᴢꜛͼᴐⱳᴒꜛ꞉ᴠᴡᴟᴦԐԓͼᴠᴒᴟꜝꞌꜝⱲᴦԓͼꜞᴟᴒⱲꜜԜꜜᴐᴦͼᴡᴒᴠᴡᴠԓͼⱪ᷈᷄ⱷ꜠ⱶͼⱱᴢꜜᴐᴡ꞉ꜝꜜԜꞌͼԜᴠᴠԜᴦԓͼⱪ᷾ͼԜᴠᴠԜᴦԓͼⱪ᷈ꜟԜᴠᴠԜᴦԓͼ͟ꜘͼ
ᴠԜꜛꜞꞌᴒᴠԓͼ͟ⱫͼᴠԜꜛꜞꞌᴒᴠԓͼԜꜜᴑͼꜞꞌԜᴠꜛԜͼԜꜜᴡ꞉᷄ᴑᴟᴢⱲͼԜꜜᴡ꞉ԝꜝᴑᴦͼᴡᴒᴠᴡ꞉ꜜⱲ᷅ͼⱨꞌꞌͼꞌԜԝꜝᴟԜᴡꜝᴟᴦͼᴡᴒᴠᴡᴠͼᴤ꞉ꞌꞌͼԝᴒͼ
ꜞᴒᴟⱱꜝᴟꜛᴒᴑͼᴢᴠ꞉ꜜⱲͼᴒᴠᴡԜԝꞌ꞉ᴠⱳᴒᴑͼԜꜜᴑͼᴣԜꞌ꞉ᴑԜᴡᴒᴑͼꜛᴒᴡⱳꜝᴑᴠ᷅ͼ
ᴄⱳᴒꜜͼꜛᴢꞌᴡ꞉ꜞꞌᴒͼᴠԜꜛꜞꞌᴒͼᴐꜝꞌꞌᴒᴐᴡ꞉ꜝꜜͼᴡᴦꜞᴒᴠͼԜᴟᴒͼꜞᴒᴟⱱꜝᴟꜛᴒᴑͼԜᴡͼᴡⱳᴒͼᴠԜꜛᴒͼԜᴠᴠᴒᴠᴠꜛᴒꜜᴡͼᴡ꞉ꜛᴒͼꜞꜝ꞉ꜜᴡԓͼᴡⱳᴒͼ
ᴠԜꜛꜞꞌᴒᴠͼᴤ꞉ꞌꞌͼԝᴒͼᴑᴟԜᴤꜜͼ꞉ꜜͼᴡⱳᴒͼⱱꜝꞌꞌꜝᴤ꞉ꜜⱲͼꜝᴟᴑᴒᴟͼӿᴑᴒꜞᴒꜜᴑ꞉ꜜⱲͼꜝꜜͼᴤⱳԜᴡͼᴠԜꜛꜞꞌᴒͼᴡᴦꜞᴒᴠͼԜᴟᴒͼᴡꜝͼԝᴒͼ
ᴐꜝꞌꞌᴒᴐᴡᴒᴑͼԜᴡͼᴡⱳԜᴡͼᴡ꞉ꜛᴒͼꜞꜝ꞉ꜜᴡԐⱡͼꞌԜԝꜝᴟԜᴡꜝᴟᴦͼᴠԜⱱᴒᴡᴦͼᴠԜꜛꜞꞌᴒᴠͼӿⱳᴒꜛԜᴡꜝꞌꜝⱲᴦԓͼᴐꜝԜⱲᴢꞌԜᴡ꞉ꜝꜜԓͼᴠᴒᴟᴢꜛͼ
ᴐⱳᴒꜛ꞉ᴠᴡᴟᴦԐԓͼⱪ᷈᷄ⱷ꜠ⱶԓͼⱪ᷾ԓͼⱪ᷈ꜟԓͼ͟ꜘԓͼԜꜜᴡ꞉᷄ᴑᴟᴢⱲͼԜꜜᴡ꞉ԝꜝᴑ꞉ᴒᴠԓͼ͟Ⱬ᷅ͼⱨꞌ꞉ꜟᴢꜝᴡᴠͼⱱᴟꜝꜛͼᴡⱳᴒͼ͟ꜘԓͼ͟ⱫͼԜꜜᴑͼԜꜜᴡ꞉᷄
ᴑᴟᴢⱲͼԜꜜᴡ꞉ԝꜝᴑᴦͼᴠԜꜛꜞꞌᴒᴠͼꜛԜᴦͼԝᴒͼᴟᴒᴡԜ꞉ꜜᴒᴑͼԜᴠͼԝԜᴐꞋ᷄ᴢꜞͼⱱꜝᴟͼԜᴑᴑ꞉ᴡ꞉ꜝꜜԜꞌͼꜞԜᴟԜꜛᴒᴡᴒᴟͼᴡᴒᴠᴡ꞉ꜜⱲͼ꞉ⱱͼꜜᴒᴐᴒᴠᴠԜᴟᴦ᷅ͼ
ᴀᴢԝ꞊ᴒᴐᴡᴠͼᴤ꞉ꞌꞌͼԝᴒͼ꞉ꜜͼԜͼᴠᴒԜᴡᴒᴑͼꜝᴟͼᴠᴢꜞ꞉ꜜᴒͼꜞꜝᴠ꞉ᴡ꞉ꜝꜜͼᴑᴢᴟ꞉ꜜⱲͼԝꞌꜝꜝᴑͼᴐꜝꞌꞌᴒᴐᴡ꞉ꜝꜜ᷅ͼᴁⱳᴒͼᴡꜝᴡԜꞌͼԝꞌꜝꜝᴑͼᴑᴟԜᴤͼⱱꜝᴟͼ
ᴒԜᴐⱳͼᴠᴢԝ꞊ᴒᴐᴡͼᴤⱳꜝͼᴑꜝᴒᴠͼꜜꜝᴡͼᴟꜝꞌꞌꜝᴣᴒᴟͼ꞉ꜜᴡꜝͼᴡⱳᴒͼ꜡ꜙⱬͼᴤ꞉ꞌꞌͼԝᴒͼԜꜞꜞᴟꜝᴥ꞉ꜛԜᴡᴒꞌᴦͼ᷉ⅎ᷈ꜛꜙ᷅ͼᴁⱳᴒͼᴡꜝᴡԜꞌͼԝꞌꜝꜝᴑͼ
ᴑᴟԜᴤͼⱱꜝᴟͼᴒԜᴐⱳͼᴠᴢԝ꞊ᴒᴐᴡͼᴡⱳԜᴡͼᴑꜝᴒᴠͼᴟꜝꞌꞌꜝᴣᴒᴟͼ꞉ꜜᴡꜝᴡⱳᴒͼ꜡ꜙⱬͼᴤ꞉ꞌꞌͼԝᴒͼԜꜞꜞᴟꜝᴥ꞉ꜛԜᴡᴒꞌᴦͼ᷉᷇˲ͼꜛꜙ᷅ͼ͟ꞌᴒԜᴠᴒͼᴟᴒⱱᴒᴟͼ
ᴡꜝͼᴡⱳᴒͼꜙԜԝꜝᴟԜᴡꜝᴟᴦͼꜚԜꜜᴢԜꞌͼⱱꜝᴟͼꜛꜝᴟᴒͼ꞉ꜜⱱꜝᴟꜛԜᴡ꞉ꜝꜜ᷅
ꜙԜԝꜝᴟԜᴡꜝᴟᴦͼᴡᴒᴠᴡ꞉ꜜⱲͼᴤ꞉ꞌꞌͼ꞉ꜜᴐꞌᴢᴑᴒͼᴡⱳᴒͼⱱꜝꞌꞌꜝᴤ꞉ꜜⱲͼԜᴠͼᴠꜞᴒᴐ꞉ⱱ꞉ᴒᴑͼ꞉ꜜͼᴡⱳᴒͼᴀᴡᴢᴑᴦͼⱨᴐᴡ꞉ᴣ꞉ᴡ꞉ᴒᴠͼᴀᴐⱳᴒᴑᴢꞌᴒͼӿᴁԜԝꞌᴒͼ
᷈Ԑ᷅
6.8.1.1
Hematology
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ⱶᴒꜛꜝⱲꞌꜝԝ꞉ꜜ

Ⱬᴅ᷄᷉Ⱡ᷊᷇
ⱪꞌ꞉ꜜ꞉ᴐԜꞌͼᴁᴟ꞉Ԝꞌͼ͟ᴟꜝᴡꜝᴐꜝꞌⱡͼⱫᴅ᷄᷉Ⱡ᷊᷊᷇᷄᷇
ⱨꜛᴒꜜᴑꜛᴒꜜᴡͼ᷊᷅᷇ͼⱴ꞉ꜜԜꞌⱡͼ᷇ⱠͼꜗԜꜜᴢԜᴟᴦ᷉᷇᷈ⅎ
ⱪꜝꜜⱱ꞉ᴑᴒꜜᴡ꞉Ԝꞌ
͟ԜⱲᴒͼ᷿᷾
ⱫᴦԜᴥͼⱪꜝᴟꜞ᷅
ᶄ
ⱶᴒꜛԜᴡꜝᴐᴟ꞉ᴡ
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ϸᴒᴑͼԝꞌꜝꜝᴑͼᴐᴒꞌꞌͼӿϸⱩⱪԐͼᴐꜝᴢꜜᴡ
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ᴄⱳ꞉ᴡᴒͼԝꞌꜝꜝᴑͼᴐᴒꞌꞌͼӿᴄⱩⱪԐͼᴐꜝᴢꜜᴡͼᴤ꞉ᴡⱳͼᴑ꞉ⱱⱱᴒᴟᴒꜜᴡ꞉Ԝꞌ
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ꜚᴒԜꜜͼᴐꜝᴟꜞᴢᴠᴐᴢꞌԜᴟͼᴣꜝꞌᴢꜛᴒͼӿꜚⱪᴃԐ
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ꜚᴒԜꜜͼᴐꜝᴟꜞᴢᴠᴐᴢꞌԜᴟͼⱳᴒꜛꜝⱲꞌꜝԝ꞉ꜜͼӿꜚⱪⱶԐ
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ꜚᴒԜꜜͼᴐꜝᴟꜞᴢᴠᴐᴢꞌԜᴟͼⱳᴒꜛꜝⱲꞌꜝԝ꞉ꜜͼᴐꜝꜜᴐᴒꜜᴡᴟԜᴡ꞉ꜝꜜͼӿꜚⱪⱶⱪԐ
ᶄ
ⱨԝᴠꜝꞌᴢᴡᴒͼꜞꞌԜᴡᴒꞌᴒᴡͼᴐꜝᴢꜜᴡ
6.8.1.2
Coagulation
ᶄ
͟ᴟꜝᴡⱳᴟꜝꜛԝ꞉ꜜͼᴡ꞉ꜛᴒͼӿ͟ᴁԐ
ᶄ
ⱨᴐᴡ꞉ᴣԜᴡᴒᴑͼꜞԜᴟᴡ꞉ԜꞌͼᴡⱳᴟꜝꜛԝꜝꜞꞌԜᴠᴡ꞉ꜜͼᴡ꞉ꜛᴒͼӿԜ͟ᴁᴁԐ
ᶄ
ⱷꜜᴡᴒᴟꜜԜᴡ꞉ꜝꜜԜꞌͼ꜠ꜝᴟꜛԜꞌ꞉ᴧᴒᴑͼϸԜᴡ꞉ꜝͼӿⱷ꜠ϸԐ
6.8.1.3
Chemistry
ᶄ
ⱨꞌԝᴢꜛ꞉ꜜ
ᶄ
ⱨꞌꞋԜꞌ꞉ꜜᴒͼꜞⱳꜝᴠꜞⱳԜᴡԜᴠᴒ
ᶄ
ⱨꞌԜꜜ꞉ꜜᴒͼԜꜛ꞉ꜜꜝᴡᴟԜꜜᴠⱱᴒᴟԜᴠᴒͼӿⱨꜙᴁⱢͼᴀⱵ͟ᴁԐ
ᶄ
ⱨᴠꜞԜᴟᴡԜᴡᴒͼԜꜛ꞉ꜜꜝᴡᴟԜꜜᴠⱱᴒᴟԜᴠᴒͼӿⱨᴀᴁⱢͼᴀⱵ꜡ᴁԐ
ᶄ
Ⱪ꞉ꞌ꞉ᴟᴢԝ꞉ꜜͼӿᴡꜝᴡԜꞌͼԜꜜᴑͼᴑ꞉ᴟᴒᴐᴡԐ
ᶄ
ⱩꞌꜝꜝᴑͼᴢᴟᴒԜͼꜜ꞉ᴡᴟꜝⱲᴒꜜͼӿⱩᴂ꜠Ԑ
ᶄ
ⱪԜꞌᴐ꞉ᴢꜛ
ᶄ
ⱪԜᴟԝꜝꜜͼᴑ꞉ꜝᴥ꞉ᴑᴒͼӿⱪ꜡᷉Ԑ
ᶄ
ⱪⱳꞌꜝᴟ꞉ᴑᴒ
ᶄ
ⱪᴟᴒԜᴡ꞉ꜜ꞉ꜜᴒ
ᶄ
ⱪᴟᴒԜᴡ꞉ꜜᴒͼꜞⱳꜝᴠꜞⱳꜝꞋ꞉ꜜԜᴠᴒͼӿⱪ͟ꜘԐ
ᶄ
Ⱶꞌᴢᴐꜝᴠᴒ
ᶄ
͟ⱳꜝᴠꜞⱳԜᴡᴒ
ᶄ
ꜚԜⱲꜜᴒᴠ꞉ᴢꜛ

Ⱬᴅ᷄᷉Ⱡ᷊᷇
ⱪꞌ꞉ꜜ꞉ᴐԜꞌͼᴁᴟ꞉Ԝꞌͼ͟ᴟꜝᴡꜝᴐꜝꞌⱡͼⱫᴅ᷄᷉Ⱡ᷊᷊᷇᷄᷇
ⱨꜛᴒꜜᴑꜛᴒꜜᴡͼ᷊᷅᷇ͼⱴ꞉ꜜԜꞌⱡͼ᷇ⱠͼꜗԜꜜᴢԜᴟᴦ᷉᷇᷈ⅎ
ⱪꜝꜜⱱ꞉ᴑᴒꜜᴡ꞉Ԝꞌ
͟ԜⱲᴒͼ᷿᷿
ⱫᴦԜᴥͼⱪꜝᴟꜞ᷅
ᶄ
͟ꜝᴡԜᴠᴠ꞉ᴢꜛ
ᶄ
ᴀꜝᴑ꞉ᴢꜛ
ᶄ
ᴁꜝᴡԜꞌͼꜞᴟꜝᴡᴒ꞉ꜜ
ᶄ
ᴂᴟ꞉ᴐͼԜᴐ꞉ᴑ
6.8.1.4
Urinalysis
ᶄ
Ⱪ꞉ꞌ꞉ᴟᴢԝ꞉ꜜ
ᶄ
Ⱶꞌᴢᴐꜝᴠᴒ
ᶄ
ꜘᴒᴡꜝꜜᴒᴠ
ᶄ
Ⱪꞌꜝꜝᴑͼ
ᶄ
꜠꞉ᴡᴟ꞉ᴡᴒ
ᶄ
ꜞⱶ
ᶄ
͟ᴟꜝᴡᴒ꞉ꜜ
ᶄ
ᴀꜞᴒᴐ꞉ⱱ꞉ᴐͼⱲᴟԜᴣ꞉ᴡᴦ
ᶄ
ꜚ꞉ᴐᴟꜝᴠᴐꜝꜞᴦͼӿ꞉ⱱͼ꞉ꜜᴑ꞉ᴐԜᴡᴒᴑͼԝᴦͼꜛԜᴐᴟꜝᴠᴐꜝꜞ꞉ᴐͼⱱ꞉ꜜᴑ꞉ꜜⱲᴠԐ
6.8.1.5
Serology
ⱶⱩᴠⱨⱲԓͼⱶⱪᴃԓͼԜꜜᴑͼⱶⱷᴃͼᴡᴒᴠᴡᴠ
6.8.1.6
Pregnancy Test
ᴀᴒᴟᴢꜛͼꜝᴟͼᴢᴟ꞉ꜜᴒͼꜞᴟᴒⱲꜜԜꜜᴐᴦͼᴡᴒᴠᴡ
6.8.1.7
C1-INH Functional Assay
ϸᴒᴠᴢꞌᴡᴠͼꜝⱱͼԜͼⱪ᷈᷄ⱷ꜠ⱶͼⱱᴢꜜᴐᴡ꞉ꜝꜜԜꞌͼԜᴠᴠԜᴦͼԜᴟᴒͼᴟᴒꜟᴢ꞉ᴟᴒᴑͼⱱꜝᴟͼᴒꞌ꞉Ⱳ꞉ԝ꞉ꞌ꞉ᴡᴦͼԜᴠᴠᴒᴠᴠꜛᴒꜜᴡ᷅ͼᴀԜꜛꜞꞌᴒᴠͼᴤ꞉ꞌꞌͼԝᴒͼ
ᴑᴟԜᴤꜜͼԜᴡͼᴡⱳᴒͼᴠᴐᴟᴒᴒꜜ꞉ꜜⱲͼᴣ꞉ᴠ꞉ᴡ᷅ͼᴀᴢԝ꞊ᴒᴐᴡᴠͼꜛԜᴦͼԝᴒͼᴟᴒᴡᴒᴠᴡᴒᴑͼ꞉ⱱͼᴟᴒᴠᴢꞌᴡᴠͼԜᴟᴒͼ꞉ꜜᴐꜝꜜⱲᴟᴢᴒꜜᴡͼᴤ꞉ᴡⱳͼᴐꞌ꞉ꜜ꞉ᴐԜꞌͼ
ⱳ꞉ᴠᴡꜝᴟᴦͼꜝᴟͼԝᴒꞌ꞉ᴒᴣᴒᴑͼԝᴦͼᴡⱳᴒͼⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟͼᴡꜝͼԝᴒͼᴐꜝꜜⱱꜝᴢꜜᴑᴒᴑͼԝᴦͼᴟᴒᴐᴒꜜᴡͼꜙᴁ͟ͼᴢᴠᴒ᷅
6.8.1.8
C4 Assay
ϸᴒᴠᴢꞌᴡᴠͼꜝⱱͼԜͼⱪ᷾ͼԜᴠᴠԜᴦͼꜛԜᴦͼԝᴒͼᴟᴒꜟᴢ꞉ᴟᴒᴑͼⱱꜝᴟͼᴒꞌ꞉Ⱳ꞉ԝ꞉ꞌ꞉ᴡᴦͼԜᴠᴠᴒᴠᴠꜛᴒꜜᴡ᷅ͼᴀԜꜛꜞꞌᴒᴠͼᴤ꞉ꞌꞌͼԝᴒͼᴑᴟԜᴤꜜͼԜᴡͼᴡⱳᴒͼ
ᴠᴐᴟᴒᴒꜜ꞉ꜜⱲͼᴣ꞉ᴠ꞉ᴡ᷅ͼᴀᴢԝ꞊ᴒᴐᴡᴠͼꜛԜᴦͼԝᴒͼᴟᴒᴡᴒᴠᴡᴒᴑͼ꞉ⱱͼᴟᴒᴠᴢꞌᴡᴠͼԜᴟᴒͼ꞉ꜜᴐꜝꜜⱲᴟᴢᴒꜜᴡͼᴤ꞉ᴡⱳͼᴐꞌ꞉ꜜ꞉ᴐԜꞌͼⱳ꞉ᴠᴡꜝᴟᴦͼꜝᴟͼ
ԝᴒꞌ꞉ᴒᴣᴒᴑͼԝᴦͼᴡⱳᴒͼⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟͼᴡꜝͼԝᴒͼᴐꜝꜜⱱꜝᴢꜜᴑᴒᴑͼԝᴦͼᴟᴒᴐᴒꜜᴡͼꜙᴁ͟ͼᴢᴠᴒ᷅ͼ

Ⱬᴅ᷄᷉Ⱡ᷊᷇
ⱪꞌ꞉ꜜ꞉ᴐԜꞌͼᴁᴟ꞉Ԝꞌͼ͟ᴟꜝᴡꜝᴐꜝꞌⱡͼⱫᴅ᷄᷉Ⱡ᷊᷊᷇᷄᷇
ⱨꜛᴒꜜᴑꜛᴒꜜᴡͼ᷊᷅᷇ͼⱴ꞉ꜜԜꞌⱡͼ᷇ⱠͼꜗԜꜜᴢԜᴟᴦ᷉᷇᷈ⅎ
ⱪꜝꜜⱱ꞉ᴑᴒꜜᴡ꞉Ԝꞌ
͟ԜⱲᴒͼ᷿⅍
ⱫᴦԜᴥͼⱪꜝᴟꜞ᷅
6.8.1.9
C1q Assay
ϸᴒᴠᴢꞌᴡᴠͼꜝⱱͼԜͼⱪ᷈ꜟͼԜᴠᴠԜᴦͼꜛԜᴦͼԝᴒͼᴟᴒꜟᴢ꞉ᴟᴒᴑͼⱱꜝᴟͼᴒꞌ꞉Ⱳ꞉ԝ꞉ꞌ꞉ᴡᴦͼԜᴠᴠᴒᴠᴠꜛᴒꜜᴡ᷅ͼᴀԜꜛꜞꞌᴒᴠͼᴤ꞉ꞌꞌͼԝᴒͼᴑᴟԜᴤꜜͼԜᴡͼᴡⱳᴒͼ
ᴠᴐᴟᴒᴒꜜ꞉ꜜⱲͼᴣ꞉ᴠ꞉ᴡ᷅ͼᴀᴢԝ꞊ᴒᴐᴡᴠͼꜛԜᴦͼԝᴒͼᴟᴒᴡᴒᴠᴡᴒᴑͼ꞉ⱱͼᴟᴒᴠᴢꞌᴡᴠͼԜᴟᴒͼ꞉ꜜᴐꜝꜜⱲᴟᴢᴒꜜᴡͼᴤ꞉ᴡⱳͼᴐꞌ꞉ꜜ꞉ᴐԜꞌͼⱳ꞉ᴠᴡꜝᴟᴦͼꜝᴟͼ
ԝᴒꞌ꞉ᴒᴣᴒᴑͼԝᴦͼᴡⱳᴒͼⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟͼᴡꜝͼԝᴒͼᴐꜝꜜⱱꜝᴢꜜᴑᴒᴑͼԝᴦͼᴟᴒᴐᴒꜜᴡͼꜙᴁ͟ͼᴢᴠᴒ᷅ͼ
6.8.1.10
PK Sample Collection
ⱨᴠͼꜝᴢᴡꞌ꞉ꜜᴒᴑͼ꞉ꜜͼᴀᴒᴐᴡ꞉ꜝꜜͼ⅍᷅Ⱡ᷅
6.8.1.11
PD Sample Collection
ⱨᴠͼꜝᴢᴡꞌ꞉ꜜᴒᴑͼ꞉ꜜͼᴀᴒᴐᴡ꞉ꜝꜜͼ⅍᷅᷈᷇᷅
6.8.1.12
Plasma Anti-Drug Antibody Testing
ⱨᴠͼꜝᴢᴡꞌ꞉ꜜᴒᴑͼ꞉ꜜͼᴀᴒᴐᴡ꞉ꜝꜜͼ⅍᷅᷈᷈᷅
6.8.2
Sample Collection, Storage, and Shipping
ⱩꞌꜝꜝᴑͼᴠԜꜛꜞꞌᴒᴠͼⱱꜝᴟͼꞌԜԝꜝᴟԜᴡꜝᴟᴦͼԜᴠᴠᴒᴠᴠꜛᴒꜜᴡᴠͼᴤ꞉ꞌꞌͼԝᴒͼᴐꜝꞌꞌᴒᴐᴡᴒᴑͼԜᴡͼᴡⱳᴒͼᴠ꞉ᴡᴒͼԝᴦͼԜͼᴡᴟԜ꞉ꜜᴒᴑͼꜞⱳꞌᴒԝꜝᴡꜝꜛ꞉ᴠᴡͼ
ᴑᴒᴠ꞉ⱲꜜԜᴡᴒᴑͼԜꜜᴑ᷆ꜝᴟͼԜꜞꜞᴟꜝᴣᴒᴑͼԝᴦͼᴡⱳᴒͼᴠᴡᴢᴑᴦͼⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟ᷅ͼⱫᴒᴡԜ꞉ꞌᴠͼⱱꜝᴟͼᴡⱳᴒͼᴐꜝꞌꞌᴒᴐᴡ꞉ꜝꜜԓͼꜞᴟꜝᴐᴒᴠᴠ꞉ꜜⱲԓͼ
ᴠᴡꜝᴟԜⱲᴒͼԜꜜᴑͼᴠⱳ꞉ꜞꜛᴒꜜᴡͼꜝⱱͼᴠԜꜛꜞꞌᴒᴠͼⱱꜝᴟͼԜꞌꞌͼꞌԜԝꜝᴟԜᴡꜝᴟᴦͼᴑᴒᴡᴒᴟꜛ꞉ꜜԜᴡ꞉ꜝꜜᴠͼᴤ꞉ꞌꞌͼԝᴒͼꜞᴟꜝᴣ꞉ᴑᴒᴑͼ꞉ꜜͼᴡⱳᴒͼ
ꜙԜԝꜝᴟԜᴡꜝᴟᴦͼꜚԜꜜᴢԜꞌ᷅
Ⱪ꞉ꜝꞌꜝⱲ꞉ᴐԜꞌͼꜛԜᴡᴒᴟ꞉Ԝꞌͼᴤ꞉ꞌꞌͼԝᴒͼᴠᴡꜝᴟᴒᴑͼԜꜜᴑͼᴠᴒᴐᴢᴟᴒᴑͼ꞉ꜜͼԜͼꜛԜꜜꜜᴒᴟͼᴡⱳԜᴡͼԜᴠᴠᴢᴟᴒᴠͼᴡⱳԜᴡͼᴢꜜԜᴢᴡⱳꜝᴟ꞉ᴧᴒᴑͼԜᴐᴐᴒᴠᴠͼ
꞉ᴠͼꜞᴟꜝⱳ꞉ԝ꞉ᴡᴒᴑͼԜꜜᴑͼᴡⱳᴒͼᴠԜꜛꜞꞌᴒᴠͼԜᴟᴒͼꜜꜝᴡͼꞌꜝᴠᴡԓͼԜꞌꞌꜝᴤᴒᴑͼᴡꜝͼᴑᴒᴡᴒᴟ꞉ꜝᴟԜᴡᴒԓͼꜝᴟͼԜᴐᴐ꞉ᴑᴒꜜᴡԜꞌꞌᴦͼꜝᴟͼ꞉ꞌꞌᴒⱲԜꞌꞌᴦͼ
ᴑᴒᴠᴡᴟꜝᴦᴒᴑ᷅ͼ
6.9
Pharmacokinetic Assessments
ⱩꞌꜝꜝᴑͼᴠԜꜛꜞꞌᴒᴠͼⱱꜝᴟͼᴡⱳᴒͼꜛᴒԜᴠᴢᴟᴒꜛᴒꜜᴡͼꜝⱱͼꜞꞌԜᴠꜛԜͼⱫᴅ᷄᷉Ⱡ᷊᷇ͼᴐꜝꜜᴐᴒꜜᴡᴟԜᴡ꞉ꜝꜜͼᴤ꞉ꞌꞌͼԝᴒͼꜝԝᴡԜ꞉ꜜᴒᴑͼԜᴡͼ
ꜞᴟᴒ᷄ᴑꜝᴠᴒͼꜝꜜͼⱫԜᴦᴠͼ᷇ԓͼ᷿⅍ᶐ᷊ԓͼⱠ˲ᶐ᷊ԓͼ᷈᷾᷇ᶐ᷊ԓͼԜꜜᴑͼ᷈˲᷉ᶐ᷊᷅ͼⱨᴑᴑ꞉ᴡ꞉ꜝꜜԜꞌͼᴠԜꜛꜞꞌᴒᴠͼᴤ꞉ꞌꞌͼԝᴒͼᴐꜝꞌꞌᴒᴐᴡᴒᴑͼꜝꜜͼ
ⱫԜᴦᴠͼ᷉᷈᷇ᶐ᷊ͼԜꜜᴑͼ᷊᷉˲ᶐ᷊ͼᴑᴢᴟ꞉ꜜⱲͼᴡⱳᴒͼⱱꜝꞌꞌꜝᴤ᷄ᴢꜞͼꜞᴒᴟ꞉ꜝᴑͼⱱꜝᴟͼԜꜜᴦͼᴠᴢԝ꞊ᴒᴐᴡᴠͼꜜꜝᴡͼᴒꜜᴡᴒᴟ꞉ꜜⱲͼ꜡ꜙⱬ᷅
6.10
Pharmacodynamic Assessments
ᴁꜝͼᴒᴣԜꞌᴢԜᴡᴒͼᴡⱳᴒͼ͟ⱫͼᴒⱱⱱᴒᴐᴡᴠͼꜝⱱͼⱫᴅ᷄᷉Ⱡ᷊᷇ͼᴢꜞꜝꜜͼꜞꞌԜᴠꜛԜͼꞋԜꞌꞌ꞉Ꞌᴟᴒ꞉ꜜͼԜᴐᴡ꞉ᴣ꞉ᴡᴦԓͼԝꞌꜝꜝᴑͼᴠԜꜛꜞꞌᴒᴠͼᴤ꞉ꞌꞌͼԝᴒͼ
ꜝԝᴡԜ꞉ꜜᴒᴑͼԜᴡͼꜞᴟᴒ᷄ᴑꜝᴠᴒͼꜝꜜͼⱫԜᴦᴠͼ᷇ԓͼ᷿⅍ᶐ᷊ԓͼⱠ˲ᶐ᷊ԓͼ᷈᷾᷇ᶐ᷊ԓͼԜꜜᴑͼ᷈˲᷉ᶐ᷊᷅ͼⱨᴑᴑ꞉ᴡ꞉ꜝꜜԜꞌͼᴠԜꜛꜞꞌᴒᴠͼᴤ꞉ꞌꞌͼԝᴒͼ
ᴐꜝꞌꞌᴒᴐᴡᴒᴑͼꜝꜜͼⱫԜᴦᴠͼ᷉᷈᷇ᶐ᷊ͼԜꜜᴑͼ᷊᷉˲ᶐ᷊ͼᴑᴢᴟ꞉ꜜⱲͼᴡⱳᴒͼⱱꜝꞌꞌꜝᴤ᷄ᴢꜞͼꜞᴒᴟ꞉ꜝᴑͼⱱꜝᴟͼԜꜜᴦͼᴠᴢԝ꞊ᴒᴐᴡᴠͼꜜꜝᴡͼᴒꜜᴡᴒᴟ꞉ꜜⱲͼ
꜡ꜙⱬ᷅
6.11
Plasma Anti-Drug Antibody Testing 
͟ꞌԜᴠꜛԜͼᴠԜꜛꜞꞌᴒᴠͼⱱꜝᴟͼᴡᴒᴠᴡ꞉ꜜⱲͼⱱꜝᴟͼⱱꜝᴟꜛԜᴡ꞉ꜝꜜͼꜝⱱͼԜꜜᴡ꞉ԝꜝᴑ꞉ᴒᴠͼᴡꜝͼⱫᴅ᷄᷉Ⱡ᷊᷇ͼᴤ꞉ꞌꞌͼԝᴒͼꜝԝᴡԜ꞉ꜜᴒᴑͼԜᴡͼꜞᴟᴒ᷄ᴑꜝᴠᴒͼ
ꜝꜜͼⱫԜᴦᴠͼ᷇ԓͼ᷿⅍ᶐ᷊ԓͼⱠ˲ᶐ᷊ԓͼ᷈᷾᷇ᶐ᷊ԓͼԜꜜᴑͼ᷈˲᷉ᶐ᷊᷅ͼⱨᴑᴑ꞉ᴡ꞉ꜝꜜԜꞌͼᴠԜꜛꜞꞌᴒᴠͼᴤ꞉ꞌꞌͼԝᴒͼᴐꜝꞌꞌᴒᴐᴡᴒᴑͼꜝꜜͼⱫԜᴦᴠͼ᷊᷉˲ᶐ᷊ͼ
ᴑᴢᴟ꞉ꜜⱲͼᴡⱳᴒͼⱱꜝꞌꞌꜝᴤ᷄ᴢꜞͼꜞᴒᴟ꞉ꜝᴑͼⱱꜝᴟͼԜꜜᴦͼᴠᴢԝ꞊ᴒᴐᴡᴠͼꜜꜝᴡͼᴒꜜᴡᴒᴟ꞉ꜜⱲͼ꜡ꜙⱬ᷅

Ⱬᴅ᷄᷉Ⱡ᷊᷇
ⱪꞌ꞉ꜜ꞉ᴐԜꞌͼᴁᴟ꞉Ԝꞌͼ͟ᴟꜝᴡꜝᴐꜝꞌⱡͼⱫᴅ᷄᷉Ⱡ᷊᷊᷇᷄᷇
ⱨꜛᴒꜜᴑꜛᴒꜜᴡͼ᷊᷅᷇ͼⱴ꞉ꜜԜꞌⱡͼ᷇ⱠͼꜗԜꜜᴢԜᴟᴦ᷉᷇᷈ⅎ
ⱪꜝꜜⱱ꞉ᴑᴒꜜᴡ꞉Ԝꞌ
͟ԜⱲᴒͼ᷿ⅎ
ⱫᴦԜᴥͼⱪꜝᴟꜞ᷅
6.12
Prior and Concomitant Therapy
ᴁⱳᴒͼᴀꜞꜝꜜᴠꜝᴟͼᴟᴒꜞᴟᴒᴠᴒꜜᴡԜᴡ꞉ᴣᴒᴠͼԜꜜᴑͼⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟͼԜᴡͼᴡⱳᴒͼᴠ꞉ᴡᴒͼᴐꜝꜜᴑᴢᴐᴡ꞉ꜜⱲͼᴡⱳᴒͼᴡᴟ꞉Ԝꞌͼᴤ꞉ꞌꞌͼᴟᴒᴣ꞉ᴒᴤͼԜꜜᴑͼ
ᴒᴣԜꞌᴢԜᴡᴒͼꜞᴟ꞉ꜝᴟͼԜꜜᴑͼᴐꜝꜜᴐꜝꜛ꞉ᴡԜꜜᴡͼꜛᴒᴑ꞉ᴐԜᴡ꞉ꜝꜜͼᴢᴠԜⱲᴒͼꜝꜜͼԜꜜͼꜝꜜⱲꜝ꞉ꜜⱲͼԝԜᴠ꞉ᴠ᷅ͼⱨꞌꞌͼꜞᴟᴒᴠᴐᴟ꞉ꜞᴡ꞉ꜝꜜԓͼꜝᴣᴒᴟ᷄ᴡⱳᴒ᷄
ᴐꜝᴢꜜᴡᴒᴟͼꜛᴒᴑ꞉ᴐԜᴡ꞉ꜝꜜᴠԓͼⱳᴒᴟԝԜꞌᴠԓͼԜꜜᴑͼᴠᴢꜞꜞꞌᴒꜛᴒꜜᴡᴠͼᴡⱳԜᴡͼԜᴟᴒͼԝᴒ꞉ꜜⱲͼᴡԜꞋᴒꜜͼꜝᴟͼⱳԜᴣᴒͼԝᴒᴒꜜͼᴡԜꞋᴒꜜͼԝᴦͼ
ᴠᴢԝ꞊ᴒᴐᴡᴠͼⱱᴟꜝꜛͼᴡⱳᴒͼᴡ꞉ꜛᴒͼꜝⱱͼᴠᴐᴟᴒᴒꜜ꞉ꜜⱲͼᴡⱳᴟꜝᴢⱲⱳͼᴡⱳᴒͼᴑᴢᴟԜᴡ꞉ꜝꜜͼꜝⱱͼᴡⱳᴒͼᴠᴡᴢᴑᴦͼᴤ꞉ꞌꞌͼԝᴒͼᴟᴒⱲԜᴟᴑᴒᴑͼԜᴠͼ
ᴐꜝꜜᴐꜝꜛ꞉ᴡԜꜜᴡͼꜛᴒᴑ꞉ᴐԜᴡ꞉ꜝꜜᴠͼԜꜜᴑͼꜛᴢᴠᴡͼԝᴒͼᴑꜝᴐᴢꜛᴒꜜᴡᴒᴑͼ꞉ꜜͼᴡⱳᴒͼᴠꜝᴢᴟᴐᴒͼᴑꜝᴐᴢꜛᴒꜜᴡᴠͼԜꜜᴑͼᴒⱪϸⱴ᷅ͼ
6.13
Randomization
ᴀᴢԝ꞊ᴒᴐᴡᴠͼᴤ꞉ꞌꞌͼԝᴒͼᴟԜꜜᴑꜝꜛ꞉ᴧᴒᴑͼ᷉ⱡ᷈ͼᴡꜝͼᴟᴒᴐᴒ꞉ᴣᴒͼᴟᴒꜞᴒԜᴡᴒᴑͼᴠᴢԝᴐᴢᴡԜꜜᴒꜝᴢᴠͼӿᴀⱪԐͼԜᴑꜛ꞉ꜜ꞉ᴠᴡᴟԜᴡ꞉ꜝꜜᴠͼꜝⱱͼⱫᴅ᷄
᷉Ⱡ᷊᷇ͼꜝᴟͼꜞꞌԜᴐᴒԝꜝͼ꞉ꜜͼԜͼᴑꜝᴢԝꞌᴒ᷄ԝꞌ꞉ꜜᴑͼⱱԜᴠⱳ꞉ꜝꜜ᷅ͼᴀᴢԝ꞊ᴒᴐᴡᴠͼᴤⱳꜝͼԜᴟᴒͼᴟԜꜜᴑꜝꜛ꞉ᴧᴒᴑͼᴡꜝͼⱫᴅ᷄᷉Ⱡ᷊᷇ͼᴤ꞉ꞌꞌͼԝᴒͼ
Ԝᴠᴠ꞉Ⱳꜜᴒᴑͼ꞉ꜜͼԜͼ᷈ⱡ᷈ⱡ᷈ͼᴟԜᴡ꞉ꜝͼᴡꜝꜝꜜᴒͼꜝⱱͼᴡⱳᴟᴒᴒͼᴑꜝᴠᴒͼᴟᴒⱲ꞉ꜛᴒꜜᴠⱡͼ᷊᷇᷇ͼꜛⱲͼᴒᴣᴒᴟᴦͼ᷉ͼᴤᴒᴒꞋᴠԓͼ᷊᷇᷇ꜛⱲͼᴒᴣᴒᴟᴦͼ᷾ͼ
ᴤᴒᴒꞋᴠͼꜝᴟͼ᷿᷈᷇ͼꜛⱲͼᴒᴣᴒᴟᴦͼ᷾ͼᴤᴒᴒꞋᴠ᷅ͼϸԜꜜᴑꜝꜛ꞉ᴧԜᴡ꞉ꜝꜜͼ꞉ꜜᴡꜝͼԜꞌꞌͼᴡᴟᴒԜᴡꜛᴒꜜᴡͼⱲᴟꜝᴢꜞᴠͼᴤ꞉ꞌꞌͼԝᴒͼᴠᴡᴟԜᴡ꞉ⱱ꞉ᴒᴑͼԝᴦͼ
ᴡⱳᴒͼԝԜᴠᴒꞌ꞉ꜜᴒͼԜᴡᴡԜᴐꞋͼᴟԜᴡᴒͼ꞉ꜜᴡꜝͼᴡⱳᴒͼⱱꜝꞌꞌꜝᴤ꞉ꜜⱲͼⱲᴟꜝᴢꜞᴠⱡͼ᷈ᴡꜝⱣ᷉ԜᴡᴡԜᴐꞋᴠͼꜞᴒᴟͼ᷾ᴤᴒᴒꞋᴠԓͼ᷉ͼᴡꜝͼⱣͼ᷊ͼԜᴡᴡԜᴐꞋᴠͼ
ꜞᴒᴟͼ᷾ͼᴤᴒᴒꞋᴠԓͼԜꜜᴑͼᶒͼ᷊ͼԜᴡᴡԜᴐꞋᴠͼꜞᴒᴟͼ᷾ͼᴤᴒᴒꞋᴠ᷅ͼ
6.14
Investigational Medicinal Product Treatment
ⱷꜜᴠᴡᴟᴢᴐᴡ꞉ꜝꜜᴠͼⱱꜝᴟͼᴠԜⱱᴒͼⱳԜꜜᴑꞌ꞉ꜜⱲͼꜝⱱͼⱷꜚ͟ԓͼꜞᴟᴒꜞԜᴟԜᴡ꞉ꜝꜜͼꜝⱱͼᴒԜᴐⱳͼᴠᴢԝᴐᴢᴡԜꜜᴒꜝᴢᴠͼᴑꜝᴠᴒԓͼԜꜜᴑͼԜᴑꜛ꞉ꜜ꞉ᴠᴡᴟԜᴡ꞉ꜝꜜͼ
ꜝⱱͼⱷꜚ͟ͼԜᴟᴒͼꜞᴟꜝᴣ꞉ᴑᴒᴑͼ꞉ꜜͼᴡⱳᴒͼ͟ⱳԜᴟꜛԜᴐᴦͼꜚԜꜜᴢԜꞌ᷅ͼ͟ᴟᴒꜞԜᴟԜᴡ꞉ꜝꜜͼԜꜜᴑͼᴑ꞉ᴠꜞᴒꜜᴠ꞉ꜜⱲꜝⱱͼᴡⱳᴒͼⱷꜚ͟ͼᴤ꞉ꞌꞌͼԝᴒͼ
ⱳԜꜜᴑꞌᴒᴑͼԝᴦͼꜟᴢԜꞌ꞉ⱱ꞉ᴒᴑͼᴠ꞉ᴡᴒͼꜞᴒᴟᴠꜝꜜꜜᴒꞌͼԜᴠͼᴑ꞉ᴟᴒᴐᴡᴒᴑͼԝᴦͼᴡⱳᴒͼ͟ᴟ꞉ꜜᴐ꞉ꜞԜꞌͼⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟͼԜᴡͼᴡⱳᴒͼᴠᴡᴢᴑᴦͼᴠ꞉ᴡᴒ᷅ͼᴁⱳᴒͼ
͟ᴟ꞉ꜜᴐ꞉ꜞԜꞌͼⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟͼꜝᴟͼꜟᴢԜꞌ꞉ⱱ꞉ᴒᴑͼᴠ꞉ᴡᴒͼꜞᴒᴟᴠꜝꜜꜜᴒꞌͼᴤ꞉ꞌꞌͼԜᴑꜛ꞉ꜜ꞉ᴠᴡᴒᴟͼᴡⱳᴒͼԜᴠᴠ꞉Ⱳꜜᴒᴑͼⱷꜚ᷅͟ͼᴁⱳᴒͼ
ᴟᴒꜟᴢ꞉ᴟᴒꜛᴒꜜᴡᴠͼⱱꜝᴟͼꜛԜ꞉ꜜᴡԜ꞉ꜜ꞉ꜜⱲͼⱷꜚ͟ͼԜᴐᴐꜝᴢꜜᴡԜԝ꞉ꞌ꞉ᴡᴦͼԜᴟᴒͼꜞᴟꜝᴣ꞉ᴑᴒᴑͼ꞉ꜜͼᴀᴒᴐᴡ꞉ꜝꜜ᷿᷅Ⱡꜝⱱͼᴡⱳ꞉ᴠͼꜞᴟꜝᴡꜝᴐꜝꞌ᷅
6.15
Quality of Life Assessments
ϷᴢԜꞌ꞉ᴡᴦͼꜝⱱͼꞌ꞉ⱱᴒͼᴑԜᴡԜͼᴤ꞉ꞌꞌͼԝᴒͼꜝԝᴡԜ꞉ꜜᴒᴑͼᴢᴠ꞉ꜜⱲͼᴡⱳᴒͼⱬᴢᴟꜝϷꜝꜙͼⱵᴟꜝᴢꜞͼ᷿᷄Ⱬ꞉ꜛᴒꜜᴠ꞉ꜝꜜͼӿⱬϷ᷿ⱫԐͼ
Ϸᴢᴒᴠᴡ꞉ꜝꜜꜜԜ꞉ᴟᴒԜᴡͼꜞᴟᴒ᷄ᴑꜝᴠᴒͼꜝꜜͼⱫԜᴦᴠͼ᷇ԓͼⱠ˲ᶐ᷊ԓͼԜꜜᴑͼ᷈˲᷉ᶐ᷊ͼԜꜜᴑͼᴢᴠ꞉ꜜⱲͼᴡⱳᴒͼⱨꜜⱲ꞉ꜝᴒᴑᴒꜛԜͼϷᴢԜꞌ꞉ᴡᴦͼꜝⱱͼ
ꜙ꞉ⱱᴒͼӿⱨⱬ᷄ϷꜝꜙԐͼϷᴢᴒᴠᴡ꞉ꜝꜜꜜԜ꞉ᴟᴒͼԜᴡͼꜞᴟᴒ᷄ᴑꜝᴠᴒͼꜝꜜͼⱫԜᴦᴠͼ᷇ԓͼ᷉˲ᶐ᷊ԓͼ᷿⅍ᶐ᷊ԓͼⱠ˲ᶐ᷊ԓͼ᷈᷉⅍ᶐ᷊ԓͼ᷿᷈᷾ᶐ᷊ԓͼԜꜜᴑͼ
᷈˲᷉ᶐ᷊᷅ͼⱨꜜͼԜᴑᴑ꞉ᴡ꞉ꜝꜜԜꞌͼꜟᴢԜꞌ꞉ᴡᴦͼꜝⱱͼꞌ꞉ⱱᴒͼԜᴠᴠᴒᴠᴠꜛᴒꜜᴡͼᴤ꞉ꞌꞌͼԝᴒͼᴐꜝꜜᴑᴢᴐᴡᴒᴑͼꜝꜜͼⱫԜᴦͼ᷊᷉˲ᶐ᷊ͼⱱꜝᴟͼᴠᴢԝ꞊ᴒᴐᴡᴠͼꜜꜝᴡͼ
ᴒꜜᴡᴒᴟ꞉ꜜⱲͼ꜡ꜙⱬ᷅
6.16
Adverse Event Reporting
ⱨᴑᴣᴒᴟᴠᴒͼᴒᴣᴒꜜᴡᴠͼᴤ꞉ꞌꞌͼԝᴒͼᴐꜝꞌꞌᴒᴐᴡᴒᴑͼⱱᴟꜝꜛͼᴠ꞉Ⱳꜜ꞉ꜜⱲꜝⱱͼᴡⱳᴒͼ꞉ꜜⱱꜝᴟꜛᴒᴑͼᴐꜝꜜᴠᴒꜜᴡͼᴡⱳᴟꜝᴢⱲⱳͼᴡⱳᴒͼꞌԜᴠᴡͼᴠᴡᴢᴑᴦͼ
ᴣ꞉ᴠ꞉ᴡ᷅
6.16.1
Definitions
6.16.1.1
Adverse Event
ⱨꜜͼⱨⱬͼ꞉ᴠͼԜꜜᴦͼᴢꜜᴡꜝᴤԜᴟᴑͼꜛᴒᴑ꞉ᴐԜꞌͼꜝᴐᴐᴢᴟᴟᴒꜜᴐᴒͼ꞉ꜜͼԜͼᴐꞌ꞉ꜜ꞉ᴐԜꞌͼᴡᴟ꞉Ԝꞌͼᴠᴢԝ꞊ᴒᴐᴡͼᴤⱳᴒᴡⱳᴒᴟͼꜝᴟͼꜜꜝᴡͼ꞉ᴡͼԜꜞꜞᴒԜᴟᴠͼᴡꜝͼ
ⱳԜᴣᴒͼԜͼᴐԜᴢᴠԜꞌͼᴟᴒꞌԜᴡ꞉ꜝꜜᴠⱳ꞉ꜞͼᴤ꞉ᴡⱳͼᴡⱳᴒͼᴡᴟᴒԜᴡꜛᴒꜜᴡͼԜᴑꜛ꞉ꜜ꞉ᴠᴡᴒᴟᴒᴑ᷅ͼ
ⱨꜜͼⱨⱬͼᴐԜꜜͼᴡⱳᴒᴟᴒⱱꜝᴟᴒͼԝᴒͼԜꜜᴦͼᴢꜜⱱԜᴣꜝᴟԜԝꞌᴒͼԜꜜᴑͼᴢꜜ꞉ꜜᴡᴒꜜᴑᴒᴑͼᴠ꞉Ⱳꜜͼӿ꞉ꜜᴐꞌᴢᴑ꞉ꜜⱲͼԜꜜͼԜԝꜜꜝᴟꜛԜꞌͼꞌԜԝꜝᴟԜᴡꜝᴟᴦͼ
ⱱ꞉ꜜᴑ꞉ꜜⱲԐԓͼᴠᴦꜛꜞᴡꜝꜛԓͼꜝᴟͼᴑ꞉ᴠᴒԜᴠᴒͼᴡᴒꜛꜞꜝᴟԜꞌꞌᴦͼԜᴠᴠꜝᴐ꞉Ԝᴡᴒᴑͼᴤ꞉ᴡⱳͼᴡⱳᴒͼᴢᴠᴒͼꜝⱱͼԜͼꜛᴒᴑ꞉ᴐ꞉ꜜԜꞌͼꜞᴟꜝᴑᴢᴐᴡͼꜝᴟͼ

Ⱬᴅ᷄᷉Ⱡ᷊᷇
ⱪꞌ꞉ꜜ꞉ᴐԜꞌͼᴁᴟ꞉Ԝꞌͼ͟ᴟꜝᴡꜝᴐꜝꞌⱡͼⱫᴅ᷄᷉Ⱡ᷊᷊᷇᷄᷇
ⱨꜛᴒꜜᴑꜛᴒꜜᴡͼ᷊᷅᷇ͼⱴ꞉ꜜԜꞌⱡͼ᷇ⱠͼꜗԜꜜᴢԜᴟᴦ᷉᷇᷈ⅎ
ⱪꜝꜜⱱ꞉ᴑᴒꜜᴡ꞉Ԝꞌ
͟ԜⱲᴒͼ᷿˲
ⱫᴦԜᴥͼⱪꜝᴟꜞ᷅
ꜞԜᴟᴡ꞉ᴐ꞉ꜞԜᴡ꞉ꜝꜜͼ꞉ꜜͼԜͼᴐꞌ꞉ꜜ꞉ᴐԜꞌͼᴠᴡᴢᴑᴦԓͼᴤⱳᴒᴡⱳᴒᴟͼꜝᴟͼꜜꜝᴡͼᴑ꞉ᴟᴒᴐᴡꞌᴦͼᴟᴒꞌԜᴡᴒᴑͼᴡꜝͼᴡⱳᴒͼꜛᴒᴑ꞉ᴐ꞉ꜜԜꞌͼꜞᴟꜝᴑᴢᴐᴡͼꜝᴟͼᴠᴡᴢᴑᴦͼ
ꜞԜᴟᴡ꞉ᴐ꞉ꜞԜᴡ꞉ꜝꜜ᷅
ᶄ
ⱨⱬᴠͼꜛԜᴦͼԝᴒͼꜜᴒᴤͼᴒᴣᴒꜜᴡᴠͼꜝᴟͼꜛԜᴦͼԝᴒͼꜞᴟᴒ᷄ᴒᴥ꞉ᴠᴡ꞉ꜜⱲͼᴐꜝꜜᴑ꞉ᴡ꞉ꜝꜜᴠͼᴡⱳԜᴡͼⱳԜᴣᴒͼԝᴒᴐꜝꜛᴒͼԜⱲⱲᴟԜᴣԜᴡᴒᴑͼꜝᴟͼ
ⱳԜᴣᴒͼᴤꜝᴟᴠᴒꜜᴒᴑͼ꞉ꜜͼᴠᴒᴣᴒᴟ꞉ᴡᴦͼꜝᴟͼⱱᴟᴒꜟᴢᴒꜜᴐᴦͼᴑᴢᴟ꞉ꜜⱲͼᴡⱳᴒͼᴐꜝᴢᴟᴠᴒͼꜝⱱͼᴡⱳᴒͼᴠᴡᴢᴑᴦ᷅
ᶄ
ⱨⱬᴠͼꜛԜᴦͼԝᴒͼᴐꞌ꞉ꜜ꞉ᴐԜꞌꞌᴦͼᴠ꞉Ⱳꜜ꞉ⱱ꞉ᴐԜꜜᴡͼᴐⱳԜꜜⱲᴒᴠͼⱱᴟꜝꜛͼԝԜᴠᴒꞌ꞉ꜜᴒͼ꞉ꜜͼꜞⱳᴦᴠ꞉ᴐԜꞌͼᴒᴥԜꜛ꞉ꜜԜᴡ꞉ꜝꜜԓͼꞌԜԝꜝᴟԜᴡꜝᴟᴦͼ
ᴡᴒᴠᴡᴠԓͼꜝᴟͼꜝᴡⱳᴒᴟͼᴑ꞉ԜⱲꜜꜝᴠᴡ꞉ᴐͼ꞉ꜜᴣᴒᴠᴡ꞉ⱲԜᴡ꞉ꜝꜜͼӿᴒ᷅Ⱳ᷅ԓͼꞌԜԝꜝᴟԜᴡꜝᴟᴦͼᴟᴒᴠᴢꞌᴡᴠԓͼᴥ᷄ᴟԜᴦͼⱱ꞉ꜜᴑ꞉ꜜⱲᴠԐ᷅
ꜙԜԝꜝᴟԜᴡꜝᴟᴦͼԜԝꜜꜝᴟꜛԜꞌ꞉ᴡ꞉ᴒᴠͼⱲᴒꜜᴒᴟԜꞌꞌᴦͼԜᴟᴒͼꜜꜝᴡͼᴐꜝꜜᴠ꞉ᴑᴒᴟᴒᴑͼⱨⱬᴠͼᴢꜜꞌᴒᴠᴠͼᴡⱳᴒᴦͼԜᴟᴒͼԜᴠᴠꜝᴐ꞉Ԝᴡᴒᴑͼᴤ꞉ᴡⱳͼ
ᴐꞌ꞉ꜜ꞉ᴐԜꞌͼᴠ꞉Ⱳꜜᴠͼꜝᴟͼᴠᴦꜛꜞᴡꜝꜛᴠԓͼꜝᴟͼᴟᴒꜟᴢ꞉ᴟᴒͼꜛᴒᴑ꞉ᴐԜꞌͼ꞉ꜜᴡᴒᴟᴣᴒꜜᴡ꞉ꜝꜜ᷅ͼⱨͼᴐꞌ꞉ꜜ꞉ᴐԜꞌꞌᴦͼᴠ꞉Ⱳꜜ꞉ⱱ꞉ᴐԜꜜᴡͼꞌԜԝꜝᴟԜᴡꜝᴟᴦͼ
ԜԝꜜꜝᴟꜛԜꞌ꞉ᴡᴦͼᴡⱳԜᴡͼ꞉ᴠͼ꞉ꜜᴑᴒꜞᴒꜜᴑᴒꜜᴡͼⱱᴟꜝꜛͼԜͼꞋꜜꜝᴤꜜͼᴢꜜᴑᴒᴟꞌᴦ꞉ꜜⱲͼꜛᴒᴑ꞉ᴐԜꞌͼᴐꜝꜜᴑ꞉ᴡ꞉ꜝꜜͼԜꜜᴑͼᴡⱳԜᴡͼᴟᴒꜟᴢ꞉ᴟᴒᴠͼ
ꜛᴒᴑ꞉ᴐԜꞌͼꜝᴟͼᴠᴢᴟⱲ꞉ᴐԜꞌͼ꞉ꜜᴡᴒᴟᴣᴒꜜᴡ꞉ꜝꜜԓͼꜝᴟͼꞌᴒԜᴑᴠͼᴡꜝͼⱷꜚ͟ͼ꞉ꜜᴡᴒᴟᴟᴢꜞᴡ꞉ꜝꜜͼꜝᴟͼᴑ꞉ᴠᴐꜝꜜᴡ꞉ꜜᴢԜᴡ꞉ꜝꜜԓͼᴤ꞉ꞌꞌԓͼ꞉ꜜͼ꞉ᴡᴠᴒꞌⱱԓͼԝᴒͼ
ᴐꜝꜜᴠ꞉ᴑᴒᴟᴒᴑͼԜꜜͼⱨⱬ᷅ͼꜙԜԝꜝᴟԜᴡꜝᴟᴦͼꜝᴟͼᴑ꞉ԜⱲꜜꜝᴠᴡ꞉ᴐͼᴡᴒᴠᴡ꞉ꜜⱲͼԜԝꜜꜝᴟꜛԜꞌ꞉ᴡ꞉ᴒᴠͼᴡⱳԜᴡͼᴟᴒⱱꞌᴒᴐᴡͼꜝᴟͼԜᴟᴒͼꜞԜᴟᴡͼꜝⱱͼԜͼ
Ꞌꜜꜝᴤꜜͼᴢꜜᴑᴒᴟꞌᴦ꞉ꜜⱲͼꜛᴒᴑ꞉ᴐԜꞌͼᴐꜝꜜᴑ꞉ᴡ꞉ꜝꜜͼԜᴟᴒͼꜜꜝᴡԓͼ꞉ꜜͼᴡⱳᴒꜛᴠᴒꞌᴣᴒᴠԓͼⱨⱬᴠⱢͼᴟԜᴡⱳᴒᴟԓͼᴡⱳᴒͼᴢꜜᴑᴒᴟꞌᴦ꞉ꜜⱲͼꜛᴒᴑ꞉ᴐԜꞌͼ
ᴐꜝꜜᴑ꞉ᴡ꞉ꜝꜜͼꞌᴒԜᴑ꞉ꜜⱲͼᴡꜝͼᴡⱳᴒͼԜԝꜜꜝᴟꜛԜꞌ꞉ᴡ꞉ᴒᴠͼᴤꜝᴢꞌᴑͼԝᴒͼᴟᴒꜞꜝᴟᴡᴒᴑͼԜᴠͼᴡⱳᴒͼⱨⱬ᷅
͟ᴟᴒⱲꜜԜꜜᴐᴦͼ꞉ᴠͼꜜꜝᴡͼԜꜜͼⱨⱬⱢͼⱳꜝᴤᴒᴣᴒᴟԓͼ꞉ⱱͼԜͼⱱᴒꜛԜꞌᴒͼᴠᴢԝ꞊ᴒᴐᴡͼԝᴒᴐꜝꜛᴒᴠͼꜞᴟᴒⱲꜜԜꜜᴡͼᴑᴢᴟ꞉ꜜⱲͼᴡⱳᴒͼᴐꜝꜜᴑᴢᴐᴡͼꜝⱱͼ
ᴡⱳᴒͼᴠᴡᴢᴑᴦԓͼᴡⱳᴒͼⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟͼꜛᴢᴠᴡͼꜜꜝᴡ꞉ⱱᴦͼᴡⱳᴒͼᴀꜞꜝꜜᴠꜝᴟͼԜᴐᴐꜝᴟᴑ꞉ꜜⱲͼᴡꜝͼᴡⱳᴒͼꜞᴟꜝᴐᴒᴑᴢᴟᴒᴠͼꜞᴟꜝᴣ꞉ᴑᴒᴑͼ꞉ꜜͼ
ᴀᴒᴐᴡ꞉ꜝꜜͼ⅍᷅᷈⅍᷿᷅᷅᷉᷅
6.16.1.2
Serious Adverse Event
ⱨͼᴀⱨⱬͼ꞉ᴠͼԜꜜᴦͼԜᴑᴣᴒᴟᴠᴒͼᴒᴥꜞᴒᴟ꞉ᴒꜜᴐᴒͼꜝᴐᴐᴢᴟᴟ꞉ꜜⱲͼԜᴡͼԜꜜᴦͼᴑꜝᴠᴒͼᴡⱳԜᴡͼᴟᴒᴠᴢꞌᴡᴠͼ꞉ꜜͼԜꜜᴦͼꜝⱱͼᴡⱳᴒͼⱱꜝꞌꞌꜝᴤ꞉ꜜⱲͼ
ꜝᴢᴡᴐꜝꜛᴒᴠⱡ
ᶄ
ⱫᴒԜᴡⱳ
ᶄ
ꜙ꞉ⱱᴒ᷄ᴡⱳᴟᴒԜᴡᴒꜜ꞉ꜜⱲͼᴒᴥꜞᴒᴟ꞉ᴒꜜᴐᴒⱢͼ꜠ꜝᴡᴒⱡͼᶰꜙ꞉ⱱᴒ᷄ᴡⱳᴟᴒԜᴡᴒꜜ꞉ꜜⱲᶱͼᴟᴒⱱᴒᴟᴠͼᴡꜝͼԜͼᴠ꞉ᴡᴢԜᴡ꞉ꜝꜜͼ꞉ꜜͼᴤⱳ꞉ᴐⱳͼᴡⱳᴒͼ
ᴠᴢԝ꞊ᴒᴐᴡͼᴤԜᴠͼԜᴡͼᴠᴢԝᴠᴡԜꜜᴡ꞉Ԝꞌͼᴟ꞉ᴠꞋͼꜝⱱͼᴑᴒԜᴡⱳͼԜᴡͼᴡⱳᴒͼᴡ꞉ꜛᴒͼꜝⱱͼᴡⱳᴒͼᴒᴣᴒꜜᴡⱢͼ꞉ᴡͼᴑꜝᴒᴠͼꜜꜝᴡͼᴟᴒⱱᴒᴟͼᴡꜝͼԜꜜͼᴒᴣᴒꜜᴡͼ
ᴡⱳԜᴡͼꜛ꞉ⱲⱳᴡͼⱳԜᴣᴒᴐԜᴢᴠᴒᴑͼᴑᴒԜᴡⱳͼ꞉ⱱͼ꞉ᴡͼᴤᴒᴟᴒͼꜛꜝᴟᴒͼᴠᴒᴣᴒᴟᴒ᷅
ᶄ
ϸᴒꜟᴢ꞉ᴟᴒᴠͼ꞉ꜜꜞԜᴡ꞉ᴒꜜᴡͼⱳꜝᴠꜞ꞉ᴡԜꞌ꞉ᴧԜᴡ꞉ꜝꜜͼꜝᴟͼꜞᴟꜝꞌꜝꜜⱲԜᴡ꞉ꜝꜜͼꜝⱱͼᴒᴥ꞉ᴠᴡ꞉ꜜⱲͼⱳꜝᴠꜞ꞉ᴡԜꞌ꞉ᴧԜᴡ꞉ꜝꜜⱢͼ꜠ꜝᴡᴒⱡͼⱫꜝᴒᴠͼꜜꜝᴡͼ
꞉ꜜᴐꞌᴢᴑᴒͼⱳꜝᴠꜞ꞉ᴡԜꞌ꞉ᴧԜᴡ꞉ꜝꜜͼⱱꜝᴟͼꜝԝᴠᴒᴟᴣԜᴡ꞉ꜝꜜͼᴤ꞉ᴡⱳͼᴟᴒꞌᴒԜᴠᴒͼᴤ꞉ᴡⱳ꞉ꜜͼ᷉᷾ͼⱳꜝᴢᴟᴠ᷅ͼⱨͼᴠᴐⱳᴒᴑᴢꞌᴒᴑͼ
ⱳꜝᴠꜞ꞉ᴡԜꞌ꞉ᴧԜᴡ꞉ꜝꜜͼⱱꜝᴟͼԜͼꜞᴟᴒ᷄ᴒᴥ꞉ᴠᴡ꞉ꜜⱲͼᴐꜝꜜᴑ꞉ᴡ꞉ꜝꜜͼᴡⱳԜᴡͼⱳԜᴠͼꜜꜝᴡͼᴤꜝᴟᴠᴒꜜᴒᴑͼᴑᴢᴟ꞉ꜜⱲͼꜞԜᴟᴡ꞉ᴐ꞉ꜞԜᴡ꞉ꜝꜜͼ꞉ꜜͼᴡⱳᴒͼ
ᴠᴡᴢᴑᴦͼᴑꜝᴒᴠͼꜜꜝᴡͼꜛᴒᴒᴡͼᴡⱳ꞉ᴠͼᴐᴟ꞉ᴡᴒᴟ꞉ꜝꜜ᷅ͼ͟ᴟᴒ᷄ꜞꞌԜꜜꜜᴒᴑͼⱳꜝᴠꜞ꞉ᴡԜꞌ꞉ᴧԜᴡ꞉ꜝꜜᴠͼⱱꜝᴟͼԜꜜͼᴒꞌᴒᴐᴡ꞉ᴣᴒͼ
ꜛᴒᴑ꞉ᴐԜꞌ᷆ᴠᴢᴟⱲ꞉ᴐԜꞌͼꜞᴟꜝᴐᴒᴑᴢᴟᴒͼꜝᴟͼᴟꜝᴢᴡ꞉ꜜᴒͼᴐⱳᴒᴐꞋ᷄ᴢꜞᴠͼᴑꜝͼꜜꜝᴡͼꜛᴒᴒᴡͼᴡⱳ꞉ᴠͼᴐᴟ꞉ᴡᴒᴟ꞉ꜝꜜ᷅
ᶄ
ϸᴒᴠᴢꞌᴡᴠͼ꞉ꜜͼꜞᴒᴟᴠ꞉ᴠᴡᴒꜜᴡͼꜝᴟͼᴠ꞉Ⱳꜜ꞉ⱱ꞉ᴐԜꜜᴡͼᴑ꞉ᴠԜԝ꞉ꞌ꞉ᴡᴦͼꜝᴟͼ꞉ꜜᴐԜꜞԜᴐ꞉ᴡᴦ᷅
ᶄ
ⱷᴠͼԜͼᴐꜝꜜⱲᴒꜜ꞉ᴡԜꞌͼԜꜜꜝꜛԜꞌᴦͼꜝᴟͼԝ꞉ᴟᴡⱳͼᴑᴒⱱᴒᴐᴡ᷅
ᶄ
ⱷᴠͼᴐꜝꜜᴠ꞉ᴑᴒᴟᴒᴑͼᴡꜝͼԝᴒͼԜꜜͼ꞉ꜛꜞꜝᴟᴡԜꜜᴡͼꜛᴒᴑ꞉ᴐԜꞌͼᴒᴣᴒꜜᴡͼᴑᴒⱱ꞉ꜜᴒᴑͼԜᴠͼᴡⱳꜝᴠᴒͼᴡⱳԜᴡͼꜛԜᴦͼꜜꜝᴡͼԝᴒͼ꞉ꜛꜛᴒᴑ꞉Ԝᴡᴒꞌᴦͼ
ꞌ꞉ⱱᴒ᷄ᴡⱳᴟᴒԜᴡᴒꜜ꞉ꜜⱲͼꜝᴟͼᴟᴒᴠᴢꞌᴡͼ꞉ꜜͼᴑᴒԜᴡⱳͼꜝᴟͼⱳꜝᴠꜞ꞉ᴡԜꞌ꞉ᴧԜᴡ꞉ꜝꜜԓͼԝᴢᴡͼꜛԜᴦͼ꞊ᴒꜝꜞԜᴟᴑ꞉ᴧᴒͼᴡⱳᴒͼᴠᴢԝ꞊ᴒᴐᴡͼꜝᴟͼꜛԜᴦͼ
ᴟᴒꜟᴢ꞉ᴟᴒͼ꞉ꜜᴡᴒᴟᴣᴒꜜᴡ꞉ꜝꜜͼᴡꜝͼꜞᴟᴒᴣᴒꜜᴡͼꜝꜜᴒͼꜝⱱͼᴡⱳᴒͼꜝᴢᴡᴐꜝꜛᴒᴠͼꞌ꞉ᴠᴡᴒᴑͼ꞉ꜜͼᴡⱳᴒͼᴑᴒⱱ꞉ꜜ꞉ᴡ꞉ꜝꜜͼԜԝꜝᴣᴒ᷅

Ⱬᴅ᷄᷉Ⱡ᷊᷇
ⱪꞌ꞉ꜜ꞉ᴐԜꞌͼᴁᴟ꞉Ԝꞌͼ͟ᴟꜝᴡꜝᴐꜝꞌⱡͼⱫᴅ᷄᷉Ⱡ᷊᷊᷇᷄᷇
ⱨꜛᴒꜜᴑꜛᴒꜜᴡͼ᷊᷅᷇ͼⱴ꞉ꜜԜꞌⱡͼ᷇ⱠͼꜗԜꜜᴢԜᴟᴦ᷉᷇᷈ⅎ
ⱪꜝꜜⱱ꞉ᴑᴒꜜᴡ꞉Ԝꞌ
͟ԜⱲᴒͼ᷿Ⱡ
ⱫᴦԜᴥͼⱪꜝᴟꜞ᷅
6.16.1.3
Overdose
ⱨꜜͼꜝᴣᴒᴟᴑꜝᴠᴒͼ꞉ᴠͼᴑᴒⱱ꞉ꜜᴒᴑͼԜᴠͼԜͼᴠ꞉Ⱳꜜ꞉ⱱ꞉ᴐԜꜜᴡͼᴣԜᴟ꞉Ԝᴡ꞉ꜝꜜͼⱱᴟꜝꜛͼᴡⱳᴒͼᴟᴒᴐꜝꜛꜛᴒꜜᴑᴒᴑ᷆ᴠᴐⱳᴒᴑᴢꞌᴒᴑͼᴑꜝᴠԜⱲᴒͼⱱꜝᴟͼԜͼ
ꜞᴟꜝᴑᴢᴐᴡ᷅ͼᴁⱳᴒͼᴑꜝᴠ꞉ꜜⱲͼⱱꜝᴟͼᴡⱳ꞉ᴠͼᴠᴡᴢᴑᴦͼᴤ꞉ꞌꞌͼԝᴒͼᴐꜝꜜᴑᴢᴐᴡᴒᴑͼ꞉ꜜͼԜͼᴐꜝꜜᴡᴟꜝꞌꞌᴒᴑͼᴐꞌ꞉ꜜ꞉ᴐԜꞌͼᴠᴒᴡᴡ꞉ꜜⱲͼԜꜜᴑͼԜꜜͼ
ꜝᴣᴒᴟᴑꜝᴠᴒͼ꞉ᴠͼꜜꜝᴡͼԜꜜᴡ꞉ᴐ꞉ꜞԜᴡᴒᴑ᷅ͼⱶꜝᴤᴒᴣᴒᴟԓͼ꞉ꜜͼᴡⱳᴒͼᴒᴣᴒꜜᴡͼꜝⱱͼԜꜜͼԜᴐᴐ꞉ᴑᴒꜜᴡԓͼⱱꜝᴟͼᴡⱳ꞉ᴠͼᴠᴡᴢᴑᴦԓͼԜꜜͼꜝᴣᴒᴟᴑꜝᴠᴒͼꜝⱱͼ
Ⱬᴅ᷄᷉Ⱡ᷊᷇ͼ꞉ᴠͼᴐꜝꜜᴠ꞉ᴑᴒᴟᴒᴑͼԜͼᴑꜝᴠᴒͼᴡⱳԜᴡͼ꞉ᴠͼᴡᴤꜝ᷄ⱱꜝꞌᴑͼⱳ꞉ⱲⱳᴒᴟͼᴡⱳԜꜜͼᴡⱳᴒͼ꞉ꜜᴡᴒꜜᴑᴒᴑͼᴑꜝᴠᴒͼⱱꜝᴟͼᴡⱳᴒͼᴠᴢԝ꞊ᴒᴐᴡ᷅
6.16.1.4
Planned Hospitalization
ⱨͼⱳꜝᴠꜞ꞉ᴡԜꞌ꞉ᴧԜᴡ꞉ꜝꜜͼꜞꞌԜꜜꜜᴒᴑͼԝᴦͼᴡⱳᴒͼᴠᴢԝ꞊ᴒᴐᴡͼꜞᴟ꞉ꜝᴟͼᴡꜝͼᴡⱳᴒͼⱱ꞉ᴟᴠᴡͼᴑꜝᴠᴒͼꜝⱱͼⱷꜚ͟ͼ꞉ᴠͼᴐꜝꜜᴠ꞉ᴑᴒᴟᴒᴑͼԜͼᴡⱳᴒᴟԜꜞᴒᴢᴡ꞉ᴐͼ
꞉ꜜᴡᴒᴟᴣᴒꜜᴡ꞉ꜝꜜͼԜꜜᴑͼꜜꜝᴡͼᴡⱳᴒͼᴟᴒᴠᴢꞌᴡͼꜝⱱͼԜͼꜜᴒᴤͼᴀⱨⱬͼԜꜜᴑͼᴠⱳꜝᴢꞌᴑͼԝᴒͼᴟᴒᴐꜝᴟᴑᴒᴑͼԜᴠͼꜛᴒᴑ꞉ᴐԜꞌͼⱳ꞉ᴠᴡꜝᴟᴦ᷅ͼⱷⱱͼᴡⱳᴒͼ
ꜞꞌԜꜜꜜᴒᴑͼⱳꜝᴠꜞ꞉ᴡԜꞌ꞉ᴧԜᴡ꞉ꜝꜜͼꜝᴟͼꜞᴟꜝᴐᴒᴑᴢᴟᴒͼ꞉ᴠͼᴒᴥᴒᴐᴢᴡᴒᴑͼԜᴠͼꜞꞌԜꜜꜜᴒᴑԓͼᴡⱳᴒͼᴟᴒᴐꜝᴟᴑͼ꞉ꜜͼᴡⱳᴒͼᴠᴢԝ꞊ᴒᴐᴡᶳᴠꜛᴒᴑ꞉ᴐԜꞌͼ
ⱳ꞉ᴠᴡꜝᴟᴦͼ꞉ᴠͼᴐꜝꜜᴠ꞉ᴑᴒᴟᴒᴑͼᴐꜝꜛꜞꞌᴒᴡᴒ᷅ͼⱶꜝᴤᴒᴣᴒᴟԓͼ꞉ⱱͼᴡⱳᴒͼᴒᴣᴒꜜᴡ᷆ᴐꜝꜜᴑ꞉ᴡ꞉ꜝꜜͼᴤꜝᴟᴠᴒꜜᴠͼᴑᴢᴟ꞉ꜜⱲͼᴡⱳᴒͼᴡᴟ꞉Ԝꞌԓͼ꞉ᴡͼꜛᴢᴠᴡͼ
ԝᴒͼᴟᴒꜞꜝᴟᴡᴒᴑͼԜᴠͼԜꜜͼⱨⱬ᷅
6.16.1.5
Treatment-Emergent Adverse Events (TEAE)
ⱨꜜͼⱨⱬͼ꞉ᴠͼᴡᴟᴒԜᴡꜛᴒꜜᴡ᷄ᴒꜛᴒᴟⱲᴒꜜᴡͼ꞉ⱱͼᴡⱳᴒͼꜝꜜᴠᴒᴡͼᴡ꞉ꜛᴒͼ꞉ᴠͼԜⱱᴡᴒᴟͼⱱ꞉ᴟᴠᴡͼԜᴑꜛ꞉ꜜ꞉ᴠᴡᴟԜᴡ꞉ꜝꜜͼꜝⱱͼⱷꜚ͟ͼᴡⱳᴟꜝᴢⱲⱳͼᴡⱳᴒͼ
ⱱ꞉ꜜԜꞌͼⱱꜝꞌꞌꜝᴤ᷄ᴢꜞͼᴣ꞉ᴠ꞉ᴡͼꜝᴟԓͼ꞉ꜜͼᴡⱳᴒͼᴒᴣᴒꜜᴡͼᴡⱳԜᴡͼꜝꜜᴠᴒᴡͼᴡ꞉ꜛᴒͼꜞᴟᴒᴐᴒᴑᴒᴠͼⱱ꞉ᴟᴠᴡͼⱷꜚ͟ͼԜᴑꜛ꞉ꜜ꞉ᴠᴡᴟԜᴡ꞉ꜝꜜԓͼᴡⱳᴒͼⱨⱬͼ
꞉ꜜᴐᴟᴒԜᴠᴒᴠͼ꞉ꜜͼᴠᴒᴣᴒᴟ꞉ᴡᴦͼᴑᴢᴟ꞉ꜜⱲͼᴡⱳᴒͼⱱꜝꞌꞌꜝᴤ᷄ᴢꜞͼꜞᴒᴟ꞉ꜝᴑ᷅
6.16.1.6
Adverse Events of Special Interest (AESI)
ⱨᴑᴣᴒᴟᴠᴒͼᴒᴣᴒꜜᴡᴠͼꜝⱱͼᴠꜞᴒᴐ꞉Ԝꞌͼ꞉ꜜᴡᴒᴟᴒᴠᴡͼӿⱨⱬᴀⱷԐͼᴤ꞉ꞌꞌͼԝᴒͼᴐԜꜞᴡᴢᴟᴒᴑͼԜꜜᴑͼꜛꜝꜜ꞉ᴡꜝᴟᴒᴑͼᴑᴢᴟ꞉ꜜⱲͼᴡⱳ꞉ᴠͼᴠᴡᴢᴑᴦ᷅ͼ
Investigators will report all AESI to the Sponsor, regardless of causality, using the same 
timelines as described for SAE reporting. ᴁⱳᴒͼⱱꜝꞌꞌꜝᴤ꞉ꜜⱲͼᴑᴒᴠᴐᴟ꞉ԝᴒͼᴡⱳᴒͼⱨⱬᴀⱷͼԜꜜᴑͼᴡⱳᴒͼᴐᴟ꞉ᴡᴒᴟ꞉Ԝͼⱱꜝᴟͼ
ᴟᴒꜞꜝᴟᴡ꞉ꜜⱲͼⱨⱬᴀⱷ᷅ͼ
HYPERSENSITIVITY REACTIONS
ⱨᴠͼⱳᴦꜞᴒᴟᴠᴒꜜᴠ꞉ᴡ꞉ᴣ꞉ᴡᴦͼᴟᴒԜᴐᴡ꞉ꜝꜜᴠͼⱳԜᴣᴒͼԝᴒᴒꜜͼꜝԝᴠᴒᴟᴣᴒᴑͼⱱꜝᴟͼꜛꜝꜜꜝᴐꞌꜝꜜԜꞌͼԜꜜᴡ꞉ԝꜝᴑ꞉ᴒᴠͼԜᴠͼԜͼᴐꞌԜᴠᴠԓͼᴡⱳᴒᴠᴒͼ
ᴒᴣᴒꜜᴡᴠͼԜᴟᴒͼᴐꜝꜜᴠ꞉ᴑᴒᴟᴒᴑͼⱨⱬᴀⱷͼⱱꜝᴟͼᴡⱳ꞉ᴠͼᴠᴡᴢᴑᴦ᷅ͼⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟᴠͼᴤ꞉ꞌꞌͼᴟᴒꜞꜝᴟᴡͼԜꞌꞌͼᴑ꞉ԜⱲꜜꜝᴠᴒᴠԓͼꜝᴟͼᴠ꞉ⱲꜜᴠͼԜꜜᴑͼ
ᴠᴦꜛꜞᴡꜝꜛᴠͼᴤⱳᴒꜜͼᴑ꞉ԜⱲꜜꜝᴠᴒᴠͼᴐԜꜜꜜꜝᴡͼԝᴒͼᴑᴒᴡᴒᴟꜛ꞉ꜜᴒᴑԓͼᴡⱳԜᴡͼԜᴟᴒͼᴐꜝꜜᴠ꞉ᴠᴡᴒꜜᴡͼᴤ꞉ᴡⱳͼⱳᴦꜞᴒᴟᴠᴒꜜᴠ꞉ᴡ꞉ᴣ꞉ᴡᴦͼ
ᴟᴒԜᴐᴡ꞉ꜝꜜᴠԓͼᴟᴒⱲԜᴟᴑꞌᴒᴠᴠͼꜝⱱͼᴐԜᴢᴠԜꞌ꞉ᴡᴦԓͼᴤ꞉ᴡⱳ꞉ꜜͼ᷉᷾ͼⱳꜝᴢᴟᴠͼⱱᴟꜝꜛͼᴡⱳᴒͼᴡ꞉ꜛᴒͼꜝⱱͼᴠᴡᴢᴑᴦͼᴑᴟᴢⱲͼԜᴑꜛ꞉ꜜ꞉ᴠᴡᴟԜᴡ꞉ꜝꜜ᷅ͼ
ⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟᴠͼᴤ꞉ꞌꞌͼᴟᴒꜞꜝᴟᴡͼⱳᴦꜞᴒᴟᴠᴒꜜᴠ꞉ᴡ꞉ᴣ꞉ᴡᴦͼᴟᴒԜᴐᴡ꞉ꜝꜜᴠͼᴡⱳԜᴡͼꜝᴐᴐᴢᴟͼԜⱱᴡᴒᴟͼ᷉᷾ͼⱳꜝᴢᴟᴠԓ ꜝꜜꞌᴦͼ꞉ⱱᴡⱳᴒͼᴟᴒԜᴐᴡ꞉ꜝꜜᴠͼ
ԜᴟᴒͼᴠᴢᴠꜞᴒᴐᴡᴒᴑͼᴡꜝͼԝᴒͼᴟᴒꞌԜᴡᴒᴑͼᴡꜝͼᴠᴡᴢᴑᴦͼᴑᴟᴢⱲ᷅ͼ
EVENTS OF DISORDERED COAGULATION
Bleeding AESI
ⱨꞌᴡⱳꜝᴢⱲⱳͼԜ͟ᴁᴁͼꜞᴟꜝꞌꜝꜜⱲԜᴡ꞉ꜝꜜͼᴑᴢᴒͼᴡꜝͼꜞꞌԜᴠꜛԜͼꞋԜꞌꞌ꞉Ꞌᴟᴒ꞉ꜜͼ꞉ꜜⱳ꞉ԝ꞉ᴡ꞉ꜝꜜͼ꞉ᴠͼԜꜜͼԜᴟᴡ꞉ⱱԜᴐᴡᴢԜꞌͼin vitro
ꜞⱳᴒꜜꜝꜛᴒꜜꜝꜜԓͼԜᴠͼԜͼꜞᴟᴒᴐԜᴢᴡ꞉ꜝꜜԜᴟᴦͼꜛᴒԜᴠᴢᴟᴒͼ꞉ꜜͼᴒᴣԜꞌᴢԜᴡ꞉ꜜⱲͼᴡⱳᴒͼᴠԜⱱᴒᴡᴦͼꜝⱱͼⱫᴅ᷄᷉Ⱡ᷊᷇ԓͼԝꞌᴒᴒᴑ꞉ꜜⱲͼᴒᴣᴒꜜᴡᴠͼ
ᴤ꞉ꞌꞌͼԝᴒͼᴟᴒꜞꜝᴟᴡᴒᴑͼԜᴠͼⱨⱬᴀⱷͼⱱꜝᴟͼᴡⱳ꞉ᴠͼᴠᴡᴢᴑᴦ᷅ͼⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟᴠͼᴤ꞉ꞌꞌͼᴟᴒꜞꜝᴟᴡͼԜꞌꞌͼᴑ꞉ԜⱲꜜꜝᴠᴒᴠԓͼꜝᴟͼᴠ꞉ⱲꜜᴠͼԜꜜᴑͼ
ᴠᴦꜛꜞᴡꜝꜛᴠͼᴤⱳᴒꜜͼᴑ꞉ԜⱲꜜꜝᴠᴒᴠͼᴐԜꜜꜜꜝᴡͼԝᴒͼᴑᴒᴡᴒᴟꜛ꞉ꜜᴒᴑԓͼᴡⱳԜᴡͼԜᴟᴒͼᴐꜝꜜᴠ꞉ᴠᴡᴒꜜᴡͼᴤ꞉ᴡⱳͼԜͼᴐꞌ꞉ꜜ꞉ᴐԜꞌͼᴒᴣᴒꜜᴡͼꜝⱱͼ
ԝꞌᴒᴒᴑ꞉ꜜⱲ᷅ͼⱪꜝԜⱲᴢꞌԜᴡ꞉ꜝꜜͼᴡᴒᴠᴡ꞉ꜜⱲͼӿԜ͟ᴁᴁԓͼ͟ᴁԓͼⱷ꜠ϸԐͼᴠⱳꜝᴢꞌᴑͼԝᴒͼꜞᴒᴟⱱꜝᴟꜛᴒᴑͼᴤⱳᴒꜜͼꜞꜝᴠᴠ꞉ԝꞌᴒԓͼԜꜜᴑͼᴤⱳᴒꜜͼ
ᴡᴒꜛꜞꜝᴟԜꞌꞌᴦͼᴟᴒԜᴠꜝꜜԜԝꞌᴒԓͼᴤ꞉ᴡⱳͼԜꜜᴦͼᴟᴒꜞꜝᴟᴡᴠͼꜝⱱͼԝꞌᴒᴒᴑ꞉ꜜⱲͼꜝᴟͼⱱꜝᴟͼᴐꞌ꞉ꜜ꞉ᴐԜꞌͼᴐꜝꜜᴑ꞉ᴡ꞉ꜝꜜᴠͼꜞꜝᴠᴠ꞉ԝꞌᴦͼ꞉ꜜᴑ꞉ᴐԜᴡ꞉ᴣᴒͼ
ꜝⱱͼԝꞌᴒᴒᴑ꞉ꜜⱲ᷅

Ⱬᴅ᷄᷉Ⱡ᷊᷇
ⱪꞌ꞉ꜜ꞉ᴐԜꞌͼᴁᴟ꞉Ԝꞌͼ͟ᴟꜝᴡꜝᴐꜝꞌⱡͼⱫᴅ᷄᷉Ⱡ᷊᷊᷇᷄᷇
ⱨꜛᴒꜜᴑꜛᴒꜜᴡͼ᷊᷅᷇ͼⱴ꞉ꜜԜꞌⱡͼ᷇ⱠͼꜗԜꜜᴢԜᴟᴦ᷉᷇᷈ⅎ
ⱪꜝꜜⱱ꞉ᴑᴒꜜᴡ꞉Ԝꞌ
͟ԜⱲᴒͼ⅍᷇
ⱫᴦԜᴥͼⱪꜝᴟꜞ᷅
Hypercoagulable AESI
ⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟᴠͼᴤ꞉ꞌꞌͼᴟᴒꜞꜝᴟᴡͼԜꞌꞌͼᴑ꞉ԜⱲꜜꜝᴠᴒᴠԓͼꜝᴟͼᴠ꞉ⱲꜜᴠͼԜꜜᴑͼᴠᴦꜛꜞᴡꜝꜛᴠͼᴤⱳᴒꜜͼᴑ꞉ԜⱲꜜꜝᴠᴒᴠͼᴐԜꜜꜜꜝᴡͼԝᴒͼ
ᴑᴒᴡᴒᴟꜛ꞉ꜜᴒᴑԓͼᴡⱳԜᴡͼԜᴟᴒͼᴐꜝꜜᴠ꞉ᴠᴡᴒꜜᴡͼᴤ꞉ᴡⱳͼԜͼᴡⱳᴟꜝꜛԝꜝᴡ꞉ᴐͼꜝᴟͼᴒꜛԝꜝꞌ꞉ᴐͼᴒᴡ꞉ꜝꞌꜝⱲᴦ᷅ͼ
6.16.2
Monitoring
6.16.2.1
Monitoring of Adverse Events
ⱬԜᴐⱳͼᴠᴢԝ꞊ᴒᴐᴡͼᴤ꞉ꞌꞌͼԝᴒͼꜛꜝꜜ꞉ᴡꜝᴟᴒᴑͼⱱꜝᴟͼᴡⱳᴒͼꜝᴐᴐᴢᴟᴟᴒꜜᴐᴒͼꜝⱱͼⱨⱬᴠԓͼ꞉ꜜᴐꞌᴢᴑ꞉ꜜⱲͼᴀⱨⱬᴠԓͼⱱᴟꜝꜛͼᴠ꞉Ⱳꜜ꞉ꜜⱲͼꜝⱱͼᴡⱳᴒͼ
ⱷⱪⱴͼᴡⱳᴟꜝᴢⱲⱳͼᴡⱳᴒͼⱱ꞉ꜜԜꞌͼⱱꜝꞌꞌꜝᴤ᷄ᴢꜞͼᴣ꞉ᴠ꞉ᴡ᷅
ᶄ
ᴀᴢԝ꞊ᴒᴐᴡᴠͼᴤ꞉ꞌꞌͼԝᴒͼꜟᴢᴒᴠᴡ꞉ꜝꜜᴒᴑͼԜꜜᴑ᷆ꜝᴟͼᴒᴥԜꜛ꞉ꜜᴒᴑͼԝᴦͼᴡⱳᴒͼⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟͼꜝᴟͼԜͼꜟᴢԜꞌ꞉ⱱ꞉ᴒᴑͼᴑᴒᴠ꞉Ⱳꜜᴒᴒͼⱱꜝᴟͼ
ᴒᴣ꞉ᴑᴒꜜᴐᴒͼꜝⱱͼⱨⱬᴠ᷅ͼᴁⱳᴒͼꜟᴢᴒᴠᴡ꞉ꜝꜜ꞉ꜜⱲͼꜝⱱͼᴠᴢԝ꞊ᴒᴐᴡᴠͼᴤ꞉ᴡⱳͼᴟᴒⱲԜᴟᴑͼᴡꜝͼᴡⱳᴒͼꜞꜝᴠᴠ꞉ԝꞌᴒͼꜝᴐᴐᴢᴟᴟᴒꜜᴐᴒͼꜝⱱͼⱨⱬᴠͼ
ᴤ꞉ꞌꞌͼԝᴒͼⱲᴒꜜᴒᴟԜꞌ꞉ᴧᴒᴑͼᴠᴢᴐⱳͼԜᴠԓͼ₭ⱶꜝᴤͼⱳԜᴣᴒͼᴦꜝᴢͼԝᴒᴒꜜͼⱱᴒᴒꞌ꞉ꜜⱲͼᴠ꞉ꜜᴐᴒͼᴦꜝᴢᴟͼꞌԜᴠᴡͼᴣ꞉ᴠ꞉ᴡⱦᶱͼͼᴁⱳᴒͼꜞᴟᴒᴠᴒꜜᴐᴒͼ
ꜝᴟͼԜԝᴠᴒꜜᴐᴒͼꜝⱱͼᴠꜞᴒᴐ꞉ⱱ꞉ᴐͼⱨⱬᴠͼᴠⱳꜝᴢꞌᴑͼꜜꜝᴡͼԝᴒͼᴒꞌ꞉ᴐ꞉ᴡᴒᴑͼⱱᴟꜝꜛͼᴠᴢԝ꞊ᴒᴐᴡᴠ᷅
ᶄ
ᴀᴢԝ꞊ᴒᴐᴡᴠͼⱳԜᴣ꞉ꜜⱲͼᴁⱬⱨⱬᴠͼᴤ꞉ꞌꞌͼԝᴒͼꜛꜝꜜ꞉ᴡꜝᴟᴒᴑͼᴢꜜᴡ꞉ꞌͼᴟᴒᴠꜝꞌᴢᴡ꞉ꜝꜜͼᴤ꞉ᴡⱳͼᴟᴒꞌᴒᴣԜꜜᴡͼᴐꞌ꞉ꜜ꞉ᴐԜꞌͼԜᴠᴠᴒᴠᴠꜛᴒꜜᴡᴠͼ
ԜꜜᴑͼꞌԜԝꜝᴟԜᴡꜝᴟᴦͼᴡᴒᴠᴡᴠԓͼԜᴠͼᴑᴒᴡᴒᴟꜛ꞉ꜜᴒᴑͼԝᴦͼᴡⱳᴒͼⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟ᷅
ᶄ
ⱨⱬᴠԓͼԜᴐᴡ꞉ꜝꜜᴠͼᴡԜꞋᴒꜜͼԜᴠͼԜͼᴟᴒᴠᴢꞌᴡͼꜝⱱͼⱨⱬᴠԓͼԜꜜᴑͼⱱꜝꞌꞌꜝᴤ᷄ᴢꜞͼᴟᴒᴠᴢꞌᴡᴠͼꜛᴢᴠᴡͼԝᴒͼᴟᴒᴐꜝᴟᴑᴒᴑͼ꞉ꜜͼᴡⱳᴒͼᴒⱪϸⱴͼԜᴠͼ
ᴤᴒꞌꞌͼԜᴠͼ꞉ꜜͼᴡⱳᴒͼᴠᴢԝ꞊ᴒᴐᴡӾᴠͼᴠꜝᴢᴟᴐᴒͼᴑꜝᴐᴢꜛᴒꜜᴡԜᴡ꞉ꜝꜜ᷅ͼⱴꜝꞌꞌꜝᴤ᷄ᴢꜞͼꞌԜԝꜝᴟԜᴡꜝᴟᴦͼᴟᴒᴠᴢꞌᴡᴠͼᴠⱳꜝᴢꞌᴑͼԝᴒͼⱱ꞉ꞌᴒᴑͼ
ᴤ꞉ᴡⱳͼᴡⱳᴒͼᴠᴢԝ꞊ᴒᴐᴡӾᴠͼᴠꜝᴢᴟᴐᴒͼᴑꜝᴐᴢꜛᴒꜜᴡԜᴡ꞉ꜝꜜ᷅
ⱴꜝᴟͼԜꜜᴦͼᴀⱨⱬᴠͼꜝᴟͼⱨⱬᴠͼᴡⱳԜᴡͼᴟᴒꜟᴢ꞉ᴟᴒͼᴡⱳᴒͼᴠᴢԝ꞊ᴒᴐᴡͼᴡꜝͼԝᴒͼᴑ꞉ᴠᴐꜝꜜᴡ꞉ꜜᴢᴒᴑͼⱱᴟꜝꜛͼᴑꜝᴠ꞉ꜜⱲԓͼᴟᴒꞌᴒᴣԜꜜᴡͼᴐꞌ꞉ꜜ꞉ᴐԜꞌͼ
ԜᴠᴠᴒᴠᴠꜛᴒꜜᴡᴠͼԜꜜᴑͼꞌԜԝꜝᴟԜᴡꜝᴟᴦͼᴡᴒᴠᴡᴠͼᴤ꞉ꞌꞌͼԝᴒͼᴟᴒꜞᴒԜᴡᴒᴑͼԜᴠͼᴐꞌ꞉ꜜ꞉ᴐԜꞌꞌᴦͼԜꜞꜞᴟꜝꜞᴟ꞉Ԝᴡᴒԓͼᴢꜜᴡ꞉ꞌͼⱱ꞉ꜜԜꞌͼᴟᴒᴠꜝꞌᴢᴡ꞉ꜝꜜͼ
ꜝᴟͼᴠᴡԜԝ꞉ꞌ꞉ᴧԜᴡ꞉ꜝꜜͼꜝⱱͼᴡⱳᴒͼᴒᴣᴒꜜᴡӿᴠԐ᷅ͼᴀᴢԝ꞊ᴒᴐᴡᴠͼᴤ꞉ꞌꞌͼᴐꜝꜜᴡ꞉ꜜᴢᴒͼᴡꜝͼԝᴒͼⱱꜝꞌꞌꜝᴤᴒᴑͼᴡⱳᴟꜝᴢⱲⱳͼᴐꜝꜛꜞꞌᴒᴡ꞉ꜝꜜͼꜝⱱͼԜꞌꞌͼ
ᴠᴐⱳᴒᴑᴢꞌᴒᴑͼᴣ꞉ᴠ꞉ᴡᴠ᷅
6.16.2.2
Monitoring of Safety Laboratory Assessments
ⱨꞌꞌͼᴠԜⱱᴒᴡᴦͼꞌԜԝꜝᴟԜᴡꜝᴟᴦͼԜᴠᴠᴒᴠᴠꜛᴒꜜᴡᴠͼᴤ꞉ꞌꞌͼԝᴒͼꜞᴒᴟⱱꜝᴟꜛᴒᴑͼԜᴡͼԜͼᴐᴒꜜᴡᴟԜꞌͼꞌԜԝꜝᴟԜᴡꜝᴟᴦ᷅ͼᴁⱳᴒͼᴐꞌ꞉ꜜ꞉ᴐԜꞌͼ
ꞌԜԝꜝᴟԜᴡꜝᴟᴦͼᴣԜꞌᴢᴒᴠͼᴤ꞉ꞌꞌͼԝᴒͼᴟᴒꜞꜝᴟᴡᴒᴑͼᴡꜝͼᴡⱳᴒͼⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟͼᴤⱳꜝͼᴤ꞉ꞌꞌͼᴟᴒᴣ꞉ᴒᴤͼᴡⱳᴒꜛͼⱱꜝᴟͼᴐꞌ꞉ꜜ꞉ᴐԜꞌͼ
ᴠ꞉Ⱳꜜ꞉ⱱ꞉ᴐԜꜜᴐᴒͼԜꜜᴑͼᴐꜝꜜᴠ꞉ᴑᴒᴟԜᴡ꞉ꜝꜜͼꜝⱱͼԜԝꜜꜝᴟꜛԜꞌͼᴣԜꞌᴢᴒᴠͼԜᴠͼꜞꜝᴡᴒꜜᴡ꞉Ԝꞌͼⱨⱬᴠ᷅
6.16.3
Assessment of Adverse Events
6.16.3.1
Assessment of Severity
ᴁⱳᴒͼᴡᴒᴟꜛͼᶰᴠᴒᴣᴒᴟᴒᶱͼ꞉ᴠͼꜝⱱᴡᴒꜜͼᴢᴠᴒᴑͼᴡꜝͼᴑᴒᴠᴐᴟ꞉ԝᴒͼᴡⱳᴒͼ꞉ꜜᴡᴒꜜᴠ꞉ᴡᴦͼӿᴠᴒᴣᴒᴟ꞉ᴡᴦԐͼꜝⱱͼԜͼᴠꜞᴒᴐ꞉ⱱ꞉ᴐͼᴒᴣᴒꜜᴡͼӿԜᴠͼ꞉ꜜͼꜛ꞉ꞌᴑԓͼ
ꜛꜝᴑᴒᴟԜᴡᴒԓ ꜝᴟͼᴠᴒᴣᴒᴟᴒͼꜛᴦꜝᴐԜᴟᴑ꞉Ԝꞌͼ꞉ꜜⱱԜᴟᴐᴡ꞉ꜝꜜԐⱢͼᴡⱳᴒͼᴒᴣᴒꜜᴡͼ꞉ᴡᴠᴒꞌⱱԓͼⱳꜝᴤᴒᴣᴒᴟԓͼꜛԜᴦͼԝᴒͼꜝⱱͼᴟᴒꞌԜᴡ꞉ᴣᴒꞌᴦͼꜛ꞉ꜜꜝᴟͼ
ꜛᴒᴑ꞉ᴐԜꞌͼᴠ꞉Ⱳꜜ꞉ⱱ꞉ᴐԜꜜᴐᴒͼӿᴠᴢᴐⱳͼԜᴠͼᴠᴒᴣᴒᴟᴒͼꜜԜᴢᴠᴒԜԐ᷅ͼᴁⱳ꞉ᴠͼ꞉ᴠͼꜜꜝᴡͼᴡⱳᴒͼᴠԜꜛᴒͼԜᴠͼᶰᴠᴒᴟ꞉ꜝᴢᴠԓᶱͼᴤⱳ꞉ᴐⱳͼ꞉ᴠͼԝԜᴠᴒᴑͼ
ꜝꜜͼᴠᴢԝ꞊ᴒᴐᴡ᷆ᴒᴣᴒꜜᴡͼꜝᴢᴡᴐꜝꜛᴒͼꜝᴟͼԜᴐᴡ꞉ꜝꜜͼᴐᴟ꞉ᴡᴒᴟ꞉ԜͼᴢᴠᴢԜꞌꞌᴦͼԜᴠᴠꜝᴐ꞉Ԝᴡᴒᴑͼᴤ꞉ᴡⱳͼᴒᴣᴒꜜᴡᴠͼᴡⱳԜᴡͼꜞꜝᴠᴒͼԜͼᴡⱳᴟᴒԜᴡͼᴡꜝͼԜͼ
ᴠᴢԝ꞊ᴒᴐᴡᶳᴠͼꞌ꞉ⱱᴒͼꜝᴟͼⱱᴢꜜᴐᴡ꞉ꜝꜜ꞉ꜜⱲ᷅
ⱷꜜͼᴡⱳ꞉ᴠͼᴠᴡᴢᴑᴦԓͼᴡⱳᴒͼᴠᴒᴣᴒᴟ꞉ᴡᴦͼꜝⱱͼⱨⱬᴠͼᴤ꞉ꞌꞌͼԝᴒͼԜᴠᴠᴒᴠᴠᴒᴑͼԜᴐᴐꜝᴟᴑ꞉ꜜⱲͼᴡꜝͼⱫ꞉ᴣ꞉ᴠ꞉ꜝꜜͼꜝⱱͼꜚ꞉ᴐᴟꜝԝ꞉ꜝꞌꜝⱲᴦͼԜꜜᴑͼ
ⱷꜜⱱᴒᴐᴡ꞉ꜝᴢᴠͼⱫ꞉ᴠᴒԜᴠᴒᴠͼӿⱫꜚⱷⱫԐͼⱨᴑᴢꞌᴡͼᴁꜝᴥ꞉ᴐ꞉ᴡᴦͼᴁԜԝꞌᴒԓͼⱫᴟԜⱱᴡԓͼ꜠ꜝᴣᴒꜛԝᴒᴟͼ᷉᷇᷇ⅎͼӿᴂᴀͼ꜠Ԝᴡ꞉ꜝꜜԜꞌͼ
ⱷꜜᴠᴡ꞉ᴡᴢᴡᴒᴠͼꜝⱱͼⱶᴒԜꞌᴡⱳⱡͼ꜠Ԝᴡ꞉ꜝꜜԜꞌͼⱷꜜᴠᴡ꞉ᴡᴢᴡᴒͼꜝⱱͼⱨꞌꞌᴒᴟⱲᴦͼԜꜜᴑͼⱷꜜⱱᴒᴐᴡ꞉ꜝᴢᴠͼⱫ꞉ᴠᴒԜᴠᴒᴠԐͼӿⱨꜞꜞᴒꜜᴑ꞉ᴥͼ᷉ԐͼԜꜜᴑͼᴡⱳᴒͼ

Ⱬᴅ᷄᷉Ⱡ᷊᷇
ⱪꞌ꞉ꜜ꞉ᴐԜꞌͼᴁᴟ꞉Ԝꞌͼ͟ᴟꜝᴡꜝᴐꜝꞌⱡͼⱫᴅ᷄᷉Ⱡ᷊᷊᷇᷄᷇
ⱨꜛᴒꜜᴑꜛᴒꜜᴡͼ᷊᷅᷇ͼⱴ꞉ꜜԜꞌⱡͼ᷇ⱠͼꜗԜꜜᴢԜᴟᴦ᷉᷇᷈ⅎ
ⱪꜝꜜⱱ꞉ᴑᴒꜜᴡ꞉Ԝꞌ
͟ԜⱲᴒͼ⅍᷈
ⱫᴦԜᴥͼⱪꜝᴟꜞ᷅
Ⱬ꞉ᴣ꞉ᴠ꞉ꜝꜜͼꜝⱱͼꜚ꞉ᴐᴟꜝԝ꞉ꜝꞌꜝⱲᴦͼԜꜜᴑͼⱷꜜⱱᴒᴐᴡ꞉ꜝᴢᴠͼⱫ꞉ᴠᴒԜᴠᴒᴠͼӿⱫꜚⱷⱫԐͼ͟ᴒᴑ꞉Ԝᴡᴟ꞉ᴐͼᴁꜝᴥ꞉ᴐ꞉ᴡᴦͼᴁԜԝꞌᴒԓͼⱫᴟԜⱱᴡԓͼ
꜠ꜝᴣᴒꜛԝᴒᴟͼ᷉᷇᷇ⅎͼӿᴂᴀͼ꜠Ԝᴡ꞉ꜝꜜԜꞌͼⱷꜜᴠᴡ꞉ᴡᴢᴡᴒᴠͼꜝⱱͼⱶᴒԜꞌᴡⱳⱡͼ꜠Ԝᴡ꞉ꜝꜜԜꞌͼⱷꜜᴠᴡ꞉ᴡᴢᴡᴒͼꜝⱱͼⱨꞌꞌᴒᴟⱲᴦͼԜꜜᴑͼⱷꜜⱱᴒᴐᴡ꞉ꜝᴢᴠͼ
Ⱬ꞉ᴠᴒԜᴠᴒᴠԐͼӿⱨꜞꜞᴒꜜᴑ꞉ᴥͼ᷊Ԑ᷅ͼⱴꜝᴟͼԜԝꜜꜝᴟꜛԜꞌ꞉ᴡ꞉ᴒᴠͼꜜꜝᴡͼᴠꜞᴒᴐ꞉ⱱ꞉ᴐԜꞌꞌᴦͼⱱꜝᴢꜜᴑͼ꞉ꜜͼᴡⱳᴒͼᴁꜝᴥ꞉ᴐ꞉ᴡᴦͼᴁԜԝꞌᴒᴠԓͼᴡⱳᴒͼ
ⱱꜝꞌꞌꜝᴤ꞉ꜜⱲͼⱲᴒꜜᴒᴟԜꞌͼᴠᴐԜꞌᴒͼᴤ꞉ꞌꞌͼԝᴒͼᴢᴠᴒᴑͼᴡꜝͼᴒᴠᴡ꞉ꜛԜᴡᴒͼⱲᴟԜᴑᴒͼꜝⱱͼᴠᴒᴣᴒᴟ꞉ᴡᴦⱡ
ᶄ
ⱵϸⱨⱫⱬͼ᷈ͼӿꜚ꞉ꞌᴑԐⱡͼᴁᴟԜꜜᴠ꞉ᴒꜜᴡͼꜝᴟͼꜛ꞉ꞌᴑͼᴑ꞉ᴠᴐꜝꜛⱱꜝᴟᴡⱢͼꜜꜝͼꜛᴒᴑ꞉ᴐԜꞌͼ꞉ꜜᴡᴒᴟᴣᴒꜜᴡ꞉ꜝꜜ᷆ᴡⱳᴒᴟԜꜞᴦͼᴟᴒꜟᴢ꞉ᴟᴒᴑ
ᶄ
ⱵϸⱨⱫⱬͼ᷉ͼӿꜚꜝᴑᴒᴟԜᴡᴒԐⱡͼꜚ꞉ꞌᴑͼᴡꜝͼꜛꜝᴑᴒᴟԜᴡᴒͼꞌ꞉ꜛ꞉ᴡԜᴡ꞉ꜝꜜͼ꞉ꜜͼԜᴐᴡ꞉ᴣ꞉ᴡᴦͼ᷄ᴠꜝꜛᴒͼԜᴠᴠ꞉ᴠᴡԜꜜᴐᴒͼꜛԜᴦͼԝᴒͼ
ꜜᴒᴒᴑᴒᴑⱢͼꜜꜝͼꜝᴟͼꜛ꞉ꜜ꞉ꜛԜꞌͼꜛᴒᴑ꞉ᴐԜꞌͼ꞉ꜜᴡᴒᴟᴣᴒꜜᴡ꞉ꜝꜜ᷆ᴡⱳᴒᴟԜꜞᴦͼᴟᴒꜟᴢ꞉ᴟᴒᴑ
ᶄ
ⱵϸⱨⱫⱬͼ᷊ͼӿᴀᴒᴣᴒᴟᴒԐⱡͼꜚԜᴟꞋᴒᴑͼꞌ꞉ꜛ꞉ᴡԜᴡ꞉ꜝꜜͼ꞉ꜜͼԜᴐᴡ꞉ᴣ꞉ᴡᴦԓͼᴠꜝꜛᴒͼԜᴠᴠ꞉ᴠᴡԜꜜᴐᴒͼᴢᴠᴢԜꞌꞌᴦͼᴟᴒꜟᴢ꞉ᴟᴒᴑⱢͼꜛᴒᴑ꞉ᴐԜꞌͼ
꞉ꜜᴡᴒᴟᴣᴒꜜᴡ꞉ꜝꜜ᷆ᴡⱳᴒᴟԜꜞᴦͼᴟᴒꜟᴢ꞉ᴟᴒᴑԓͼⱳꜝᴠꜞ꞉ᴡԜꞌ꞉ᴧԜᴡ꞉ꜝꜜᴠͼꜞꜝᴠᴠ꞉ԝꞌᴒͼ
ᶄ
ⱵϸⱨⱫⱬͼ᷾ͼӿꜙ꞉ⱱᴒ᷄ᴡⱳᴟᴒԜᴡᴒꜜ꞉ꜜⱲԐⱡͼⱬᴥᴡᴟᴒꜛᴒͼꞌ꞉ꜛ꞉ᴡԜᴡ꞉ꜝꜜͼ꞉ꜜͼԜᴐᴡ꞉ᴣ꞉ᴡᴦԓͼᴠ꞉Ⱳꜜ꞉ⱱ꞉ᴐԜꜜᴡͼԜᴠᴠ꞉ᴠᴡԜꜜᴐᴒͼᴟᴒꜟᴢ꞉ᴟᴒᴑⱢͼ
ᴠ꞉Ⱳꜜ꞉ⱱ꞉ᴐԜꜜᴡͼꜛᴒᴑ꞉ᴐԜꞌͼ꞉ꜜᴡᴒᴟᴣᴒꜜᴡ꞉ꜝꜜ᷆ᴡⱳᴒᴟԜꜞᴦͼᴟᴒꜟᴢ꞉ᴟᴒᴑԓͼⱳꜝᴠꜞ꞉ᴡԜꞌ꞉ᴧԜᴡ꞉ꜝꜜͼꜝᴟͼⱳꜝᴠꜞ꞉ᴐᴒͼᴐԜᴟᴒͼꜞᴟꜝԝԜԝꞌᴒ
ⱨꜜᴦͼᴡᴟᴒԜᴡꜛᴒꜜᴡ᷄ᴒꜛᴒᴟⱲᴒꜜᴡͼⱬⱪⱵͼԜԝꜜꜝᴟꜛԜꞌ꞉ᴡᴦͼᴡⱳԜᴡͼ꞉ᴠͼᴐꜝꜜᴠ꞉ᴑᴒᴟᴒᴑͼԝᴦͼᴡⱳᴒͼⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟͼԜᴠͼᴐꞌ꞉ꜜ꞉ᴐԜꞌꞌᴦͼ
ᴠ꞉Ⱳꜜ꞉ⱱ꞉ᴐԜꜜᴡͼԜꜜᴑͼᴟᴒꜟᴢ꞉ᴟ꞉ꜜⱲͼ꞉ꜜᴡᴒᴟᴣᴒꜜᴡ꞉ꜝꜜ᷆ᴡⱳᴒᴟԜꜞᴦͼᴤ꞉ꞌꞌͼԝᴒͼԜᴠᴠᴒᴠᴠᴒᴑͼԜᴠͼԜͼᴠᴒᴣᴒᴟᴒͼⱨⱬ᷅
6.16.3.2
Assessment of Causality
ⱨͼꜛᴒᴑ꞉ᴐԜꞌꞌᴦͼꜟᴢԜꞌ꞉ⱱ꞉ᴒᴑͼⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟͼꜛᴢᴠᴡͼԜᴠᴠᴒᴠᴠͼᴡⱳᴒͼᴟᴒꞌԜᴡ꞉ꜝꜜᴠⱳ꞉ꜞͼꜝⱱͼԜꜜᴦͼⱨⱬͼӿ꞉ꜜᴐꞌᴢᴑ꞉ꜜⱲͼᴀⱨⱬᴠԐͼᴡꜝͼ
ᴡⱳᴒͼᴢᴠᴒͼꜝⱱͼᴡⱳᴒͼⱷꜚ͟ԓͼԜᴠͼᴟᴒꞌԜᴡᴒᴑͼꜝᴟͼꜜꜝᴡͼᴟᴒꞌԜᴡᴒᴑԓͼԝԜᴠᴒᴑͼꜝꜜͼᴐꞌ꞉ꜜ꞉ᴐԜꞌͼ꞊ᴢᴑⱲꜛᴒꜜᴡͼԜꜜᴑͼᴢᴠ꞉ꜜⱲͼԜꞌꞌͼԜᴣԜ꞉ꞌԜԝꞌᴒͼ
꞉ꜜⱱꜝᴟꜛԜᴡ꞉ꜝꜜԓͼԜꜜᴑͼꜛԜᴦͼ꞉ꜜᴐꞌᴢᴑᴒͼᴐꜝꜜᴠ꞉ᴑᴒᴟԜᴡ꞉ꜝꜜͼꜝⱱᴡⱳᴒͼⱱꜝꞌꞌꜝᴤ꞉ꜜⱲͼⱱԜᴐᴡꜝᴟᴠⱡ
ᶄ
͟ꜝᴠᴠ꞉ԝꞌᴒͼԜꞌᴡᴒᴟꜜԜᴡ꞉ᴣᴒͼᴐԜᴢᴠᴒᴠͼꜝⱱͼᴡⱳᴒͼⱨⱬԓͼ꞉ꜜᴐꞌᴢᴑ꞉ꜜⱲͼᴡⱳᴒͼᴑ꞉ᴠᴒԜᴠᴒͼᴢꜜᴑᴒᴟͼᴡᴟᴒԜᴡꜛᴒꜜᴡԓͼꜞᴟᴒ᷄ᴒᴥ꞉ᴠᴡ꞉ꜜⱲͼ
ᴐꜝꜜᴑ꞉ᴡ꞉ꜝꜜᴠԓͼᴐꜝꜜᴐꜝꜛ꞉ᴡԜꜜᴡͼᴢᴠᴒͼꜝⱱͼꜝᴡⱳᴒᴟͼᴑᴟᴢⱲᴠԓͼԜꜜᴑͼꜞᴟᴒᴠᴒꜜᴐᴒͼꜝⱱͼᴒꜜᴣ꞉ᴟꜝꜜꜛᴒꜜᴡԜꞌͼꜝᴟͼⱲᴒꜜᴒᴡ꞉ᴐͼⱱԜᴐᴡꜝᴟᴠ᷅
ᶄ
ᴁⱳᴒͼᴡᴒꜛꜞꜝᴟԜꞌͼԜᴠᴠꜝᴐ꞉Ԝᴡ꞉ꜝꜜͼԝᴒᴡᴤᴒᴒꜜͼⱷꜚ͟ͼᴒᴥꜞꜝᴠᴢᴟᴒͼԜꜜᴑͼꜝꜜᴠᴒᴡͼꜝⱱͼᴡⱳᴒͼⱨⱬ᷅
ᶄ
ᴄⱳᴒᴡⱳᴒᴟͼᴡⱳᴒͼꜛԜꜜ꞉ⱱᴒᴠᴡԜᴡ꞉ꜝꜜᴠͼꜝⱱͼᴡⱳᴒͼⱨⱬͼԜᴟᴒͼᴐꜝꜜᴠ꞉ᴠᴡᴒꜜᴡͼᴤ꞉ᴡⱳͼꞋꜜꜝᴤꜜͼԜᴐᴡ꞉ꜝꜜᴠͼꜝᴟͼᴡꜝᴥ꞉ᴐ꞉ᴡᴦͼꜝⱱͼᴡⱳᴒͼ
ⱷꜚ᷅͟
ᶄ
ᴁⱳᴒͼⱨⱬͼᴟᴒᴠꜝꞌᴣᴒᴑͼꜝᴟͼ꞉ꜛꜞᴟꜝᴣᴒᴑͼᴤ꞉ᴡⱳͼᴑᴒᴐᴟᴒԜᴠ꞉ꜜⱲͼᴡⱳᴒͼᴑꜝᴠᴒͼꜝᴟͼᴠᴡꜝꜞꜞ꞉ꜜⱲͼᴢᴠᴒͼꜝⱱͼᴡⱳᴒͼⱷꜚ͟ͼ
ӿᴑᴒᴐⱳԜꞌꞌᴒꜜⱲᴒԐ᷅ͼꜗᴢᴑⱲꜛᴒꜜᴡͼᴠⱳꜝᴢꞌᴑͼԝᴒͼᴢᴠᴒᴑͼ꞉ⱱͼꜛᴢꞌᴡ꞉ꜞꞌᴒͼꜞᴟꜝᴑᴢᴐᴡᴠͼԜᴟᴒͼᴑ꞉ᴠᴐꜝꜜᴡ꞉ꜜᴢᴒᴑͼԜᴡͼᴡⱳᴒͼᴠԜꜛᴒͼ
ᴡ꞉ꜛᴒ᷅
ᴁⱳᴒͼᴐԜᴢᴠԜꞌͼᴟᴒꞌԜᴡ꞉ꜝꜜᴠⱳ꞉ꜞͼԝᴒᴡᴤᴒᴒꜜͼᴡⱳᴒͼᴠᴡᴢᴑᴦͼⱷꜚ͟ͼԜꜜᴑͼᴡⱳᴒͼⱨⱬͼᴤ꞉ꞌꞌͼԝᴒͼԜᴠᴠᴒᴠᴠᴒᴑͼᴢᴠ꞉ꜜⱲͼꜝꜜᴒͼꜝⱱͼᴡⱳᴒͼ
ⱱꜝꞌꞌꜝᴤ꞉ꜜⱲͼᴐԜᴡᴒⱲꜝᴟ꞉ᴒᴠⱡ
Not Related:ͼͼⱴԜᴐᴡꜝᴟᴠͼᴐꜝꜜᴠ꞉ᴠᴡᴒꜜᴡͼᴤ꞉ᴡⱳͼԜꜜͼԜᴠᴠᴒᴠᴠꜛᴒꜜᴡͼꜝⱱͼ꜠ꜝᴡͼϸᴒꞌԜᴡᴒᴑͼ꞉ꜜᴐꞌᴢᴑᴒⱡ

ᴁᴒꜛꜞꜝᴟԜꞌͼᴟᴒꞌԜᴡ꞉ꜝꜜᴠⱳ꞉ꜞͼ꞉ᴠͼꞌԜᴐꞋ꞉ꜜⱲͼӿᴒ᷅Ⱳ᷅ԓͼᴡⱳᴒͼᴒᴣᴒꜜᴡͼᴑ꞉ᴑͼꜜꜝᴡͼꜝᴐᴐᴢᴟͼᴤ꞉ᴡⱳ꞉ꜜͼԜͼᴟᴒԜᴠꜝꜜԜԝꞌᴒͼ
ᴡ꞉ꜛᴒͼⱱᴟԜꜛᴒͼⱱꜝꞌꞌꜝᴤ꞉ꜜⱲͼԜᴑꜛ꞉ꜜ꞉ᴠᴡᴟԜᴡ꞉ꜝꜜͼꜝⱱͼᴡⱳᴒͼⱷꜚ͟ԐⱢͼꜝᴟ

Ⱬᴅ᷄᷉Ⱡ᷊᷇
ⱪꞌ꞉ꜜ꞉ᴐԜꞌͼᴁᴟ꞉Ԝꞌͼ͟ᴟꜝᴡꜝᴐꜝꞌⱡͼⱫᴅ᷄᷉Ⱡ᷊᷊᷇᷄᷇
ⱨꜛᴒꜜᴑꜛᴒꜜᴡͼ᷊᷅᷇ͼⱴ꞉ꜜԜꞌⱡͼ᷇ⱠͼꜗԜꜜᴢԜᴟᴦ᷉᷇᷈ⅎ
ⱪꜝꜜⱱ꞉ᴑᴒꜜᴡ꞉Ԝꞌ
͟ԜⱲᴒͼ⅍᷉
ⱫᴦԜᴥͼⱪꜝᴟꜞ᷅

꜡ᴡⱳᴒᴟͼᴐԜᴢᴠԜᴡ꞉ᴣᴒͼⱱԜᴐᴡꜝᴟᴠͼꜛꜝᴟᴒͼꞌ꞉ꞋᴒꞌᴦͼᴒᴥꜞꞌԜ꞉ꜜͼᴡⱳᴒͼᴒᴣᴒꜜᴡͼӿᴒ᷅Ⱳ᷅ԓͼԜͼꜞᴟᴒ᷄ᴒᴥ꞉ᴠᴡ꞉ꜜⱲͼ
ᴐꜝꜜᴑ꞉ᴡ꞉ꜝꜜԓͼꜝᴡⱳᴒᴟͼᴐꜝꜜᴐꜝꜛ꞉ᴡԜꜜᴡͼᴡᴟᴒԜᴡꜛᴒꜜᴡᴠԐ᷅
Related:ͼͼⱴԜᴐᴡꜝᴟᴠͼᴐꜝꜜᴠ꞉ᴠᴡᴒꜜᴡͼᴤ꞉ᴡⱳͼԜꜜͼԜᴠᴠᴒᴠᴠꜛᴒꜜᴡͼꜝⱱͼϸᴒꞌԜᴡᴒᴑͼ꞉ꜜᴐꞌᴢᴑᴒⱡ

ᴁⱳᴒᴟᴒͼ꞉ᴠͼԜͼꜞꜝᴠ꞉ᴡ꞉ᴣᴒͼᴡᴒꜛꜞꜝᴟԜꞌͼᴟᴒꞌԜᴡ꞉ꜝꜜᴠⱳ꞉ꜞͼӿᴒ᷅Ⱳ᷅ԓͼᴡⱳᴒͼᴒᴣᴒꜜᴡͼꜝᴐᴐᴢᴟᴟᴒᴑͼᴤ꞉ᴡⱳ꞉ꜜͼԜͼ
ᴟᴒԜᴠꜝꜜԜԝꞌᴒͼᴡ꞉ꜛᴒͼⱱᴟԜꜛᴒͼⱱꜝꞌꞌꜝᴤ꞉ꜜⱲͼԜᴑꜛ꞉ꜜ꞉ᴠᴡᴟԜᴡ꞉ꜝꜜͼꜝⱱͼⱷꜚ͟ԐⱢͼꜝᴟ

ᴁⱳᴒͼⱨⱬͼ꞉ᴠͼꜛꜝᴟᴒͼꞌ꞉ꞋᴒꞌᴦͼᴒᴥꜞꞌԜ꞉ꜜᴒᴑͼԝᴦͼᴡⱳᴒͼ꞉ꜜᴣᴒᴠᴡ꞉ⱲԜᴡ꞉ꜝꜜԜꞌͼꜞᴟꜝᴑᴢᴐᴡͼᴡⱳԜꜜͼԝᴦͼԜꜜꜝᴡⱳᴒᴟͼ
ᴐԜᴢᴠᴒͼӿ꞉᷅ᴒ᷅ԓͼᴡⱳᴒͼⱨⱬͼᴠⱳꜝᴤᴠͼԜͼꜞԜᴡᴡᴒᴟꜜͼᴐꜝꜜᴠ꞉ᴠᴡᴒꜜᴡͼᴤ꞉ᴡⱳͼꜞᴟᴒᴣ꞉ꜝᴢᴠͼꞋꜜꜝᴤꞌᴒᴑⱲᴒͼꜝⱱͼᴡⱳᴒͼ
꞉ꜜᴣᴒᴠᴡ꞉ⱲԜᴡ꞉ꜝꜜԜꞌͼꜞᴟꜝᴑᴢᴐᴡͼꜝᴟͼᴡⱳᴒͼᴐꞌԜᴠᴠͼꜝⱱͼᴡⱳᴒͼⱷꜚ͟Ԑ᷅
6.16.3.3
Assessment of Clinical Significance
ⱪꞌ꞉ꜜ꞉ᴐԜꞌͼᴠ꞉Ⱳꜜ꞉ⱱ꞉ᴐԜꜜᴐᴒͼꜝⱱͼ꞉ꜜᴑ꞉ᴣ꞉ᴑᴢԜꞌͼⱨⱬᴠͼᴤ꞉ꞌꞌͼԝᴒͼᴑᴒᴡᴒᴟꜛ꞉ꜜᴒᴑͼԝᴦͼᴡⱳᴒͼⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟԓͼᴤ꞉ᴡⱳͼᴑ꞉ᴠᴐᴢᴠᴠ꞉ꜝꜜͼ
ᴤ꞉ᴡⱳͼᴡⱳᴒͼꜚᴒᴑ꞉ᴐԜꞌͼꜚꜝꜜ꞉ᴡꜝᴟͼԜᴠͼԜꜞꜞᴟꜝꜞᴟ꞉ԜᴡᴒԓͼꜝᴟͼԝᴦͼᴡⱳᴒͼⱫᴀꜚⱩͼⱱꜝᴟͼꜝᴣᴒᴟԜꞌꞌͼᴠᴡᴢᴑᴦͼⱨⱬͼᴟᴒᴣ꞉ᴒᴤ᷅
6.16.4
Clinical Laboratory Adverse Events
ꜙԜԝꜝᴟԜᴡꜝᴟᴦͼԜԝꜜꜝᴟꜛԜꞌ꞉ᴡ꞉ᴒᴠͼⱲᴒꜜᴒᴟԜꞌꞌᴦͼԜᴟᴒͼꜜꜝᴡͼᴐꜝꜜᴠ꞉ᴑᴒᴟᴒᴑͼⱨⱬᴠͼᴢꜜꞌᴒᴠᴠͼᴡⱳᴒᴦͼԜᴟᴒͼԜᴠᴠꜝᴐ꞉Ԝᴡᴒᴑͼᴤ꞉ᴡⱳͼ
ᴐꞌ꞉ꜜ꞉ᴐԜꞌͼᴠ꞉Ⱳꜜᴠͼꜝᴟͼᴠᴦꜛꜞᴡꜝꜛᴠԓͼꜝᴟͼᴟᴒꜟᴢ꞉ᴟᴒͼꜛᴒᴑ꞉ᴐԜꞌͼ꞉ꜜᴡᴒᴟᴣᴒꜜᴡ꞉ꜝꜜ᷅ͼⱨͼᴐꞌ꞉ꜜ꞉ᴐԜꞌꞌᴦͼᴠ꞉Ⱳꜜ꞉ⱱ꞉ᴐԜꜜᴡͼꞌԜԝꜝᴟԜᴡꜝᴟᴦͼ
ԜԝꜜꜝᴟꜛԜꞌ꞉ᴡᴦͼᴡⱳԜᴡͼ꞉ᴠͼ꞉ꜜᴑᴒꜞᴒꜜᴑᴒꜜᴡͼⱱᴟꜝꜛͼԜͼꞋꜜꜝᴤꜜͼᴢꜜᴑᴒᴟꞌᴦ꞉ꜜⱲͼꜛᴒᴑ꞉ᴐԜꞌͼᴐꜝꜜᴑ꞉ᴡ꞉ꜝꜜͼԜꜜᴑͼᴡⱳԜᴡͼᴟᴒꜟᴢ꞉ᴟᴒᴠͼ
ꜛᴒᴑ꞉ᴐԜꞌͼꜝᴟͼᴠᴢᴟⱲ꞉ᴐԜꞌͼ꞉ꜜᴡᴒᴟᴣᴒꜜᴡ꞉ꜝꜜԓͼꜝᴟͼꞌᴒԜᴑᴠͼᴡꜝͼⱷꜚ͟ͼ꞉ꜜᴡᴒᴟᴟᴢꜞᴡ꞉ꜝꜜͼꜝᴟͼᴑ꞉ᴠᴐꜝꜜᴡ꞉ꜜᴢԜᴡ꞉ꜝꜜԓͼᴤ꞉ꞌꞌͼԝᴒͼ
ᴐꜝꜜᴠ꞉ᴑᴒᴟᴒᴑͼԜꜜͼⱨⱬ᷅
ᴄⱳᴒꜜͼꞌԜԝꜝᴟԜᴡꜝᴟᴦͼԜԝꜜꜝᴟꜛԜꞌ꞉ᴡ꞉ᴒᴠͼԜᴟᴒͼᴐꜝꜜᴠ꞉ᴑᴒᴟᴒᴑͼᴡꜝͼԝᴒͼⱨⱬᴠԓͼᴡⱳᴒͼⱫꜚⱷⱫͼⱨᴑᴢꞌᴡͼᴁꜝᴥ꞉ᴐ꞉ᴡᴦͼᴁԜԝꞌᴒͼ
ӿⱨꜞꜞᴒꜜᴑ꞉ᴥͼ᷉ԐͼꜝᴟͼⱫꜚⱷⱫͼ͟ᴒᴑ꞉Ԝᴡᴟ꞉ᴐͼᴁꜝᴥ꞉ᴐ꞉ᴡᴦͼᴁԜԝꞌᴒᴠͼӿⱨꜞꜞᴒꜜᴑ꞉ᴥͼ᷊Ԑͼᴤ꞉ꞌꞌͼԝᴒͼᴢᴠᴒᴑͼᴡꜝͼԜᴠᴠᴒᴠᴠͼᴠᴒᴣᴒᴟ꞉ᴡᴦ᷅ͼ
ᴄⱳᴒᴟᴒͼᴑ꞉ᴠᴐᴟᴒꜞԜꜜᴐ꞉ᴒᴠͼ꞉ꜜͼᴡⱳᴒͼᴢꜞꜞᴒᴟͼꞌ꞉ꜛ꞉ᴡͼꜝⱱͼꜜꜝᴟꜛԜꞌͼӿᴂꜙ꜠ԐͼԜꜜᴑͼꞌꜝᴤᴒᴟͼꞌ꞉ꜛ꞉ᴡͼꜝⱱͼꜜꜝᴟꜛԜꞌͼӿꜙꜙ꜠Ԑͼꜝⱱͼ
ꞌԜԝꜝᴟԜᴡꜝᴟᴦͼᴟԜꜜⱲᴒᴠͼꜝᴐᴐᴢᴟͼԝᴒᴡᴤᴒᴒꜜͼᴡⱳꜝᴠᴒͼ꞉ꜜᴐꞌᴢᴑᴒᴑͼ꞉ꜜͼᴡⱳᴒͼⱫꜚⱷⱫͼᴡԜԝꞌᴒᴠͼԜꜜᴑͼᴡⱳꜝᴠᴒͼꜝⱱͼᴡⱳᴒͼꞌԜԝꜝᴟԜᴡꜝᴟᴦͼ
ᴡⱳԜᴡͼꜞᴒᴟⱱꜝᴟꜛᴠͼᴡⱳᴒͼԜᴠᴠԜᴦᴠԓͼᴡⱳᴒͼᴣԜꞌᴢᴒᴠͼꜞᴟꜝᴣ꞉ᴑᴒᴑͼԝᴦͼᴡⱳᴒͼꞌԜԝꜝᴟԜᴡꜝᴟᴦͼᴤ꞉ꞌꞌͼԝᴒͼᴢᴠᴒᴑͼⱱꜝᴟͼԜᴠᴠ꞉Ⱳꜜꜛᴒꜜᴡͼꜝⱱͼ
ᴠᴒᴣᴒᴟ꞉ᴡᴦͼⱲᴟԜᴑᴒ᷅ͼⱪꞌ꞉ꜜ꞉ᴐԜꞌͼᴠ꞉Ⱳꜜ꞉ⱱ꞉ᴐԜꜜᴐᴒͼꜝⱱͼ꞉ꜜᴑ꞉ᴣ꞉ᴑᴢԜꞌͼꞌԜԝꜝᴟԜᴡꜝᴟᴦͼⱨⱬᴠͼᴤ꞉ꞌꞌͼԝᴒͼᴑᴒᴡᴒᴟꜛ꞉ꜜᴒᴑͼԝᴦͼᴡⱳᴒͼ
ⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟͼᴤ꞉ᴡⱳͼ꞉ꜜꜞᴢᴡͼⱱᴟꜝꜛͼᴡⱳᴒͼꜚᴒᴑ꞉ᴐԜꞌͼꜚꜝꜜ꞉ᴡꜝᴟͼԜᴠͼꜜᴒᴒᴑᴒᴑ᷅ͼ
ⱴꜝꞌꞌꜝᴤ꞉ꜜⱲͼ꞉ᴠͼԜꜜͼᴒᴥᴐᴒꜞᴡ꞉ꜝꜜͼᴡꜝͼᴑᴒⱱ꞉ꜜ꞉ꜜⱲͼᴐꞌ꞉ꜜ꞉ᴐԜꞌꞌᴦͼᴠ꞉Ⱳꜜ꞉ⱱ꞉ᴐԜꜜᴡԓͼԜԝꜜꜝᴟꜛԜꞌͼꞌԜԝꜝᴟԜᴡꜝᴟᴦͼᴣԜꞌᴢᴒᴠͼԜᴠͼⱨⱬᴠⱡ

ⱨ͟ᴁᴁͼꜞᴟꜝꞌꜝꜜⱲԜᴡ꞉ꜝꜜͼ꞉ꜜͼᴡⱳᴒͼԜԝᴠᴒꜜᴐᴒͼꜝⱱͼԜꜜᴦͼԜᴠᴠꜝᴐ꞉Ԝᴡᴒᴑͼԝꞌᴒᴒᴑ꞉ꜜⱲͼꜝᴟͼꜝᴡⱳᴒᴟͼᴒᴣ꞉ᴑᴒꜜᴐᴒͼꜝⱱͼᴐꞌ꞉ꜜ꞉ᴐԜꞌͼ
ᴟᴒꞌᴒᴣԜꜜᴐᴒͼᴤ꞉ꞌꞌͼꜜꜝᴡͼԝᴒͼᴐꜝꜜᴠ꞉ᴑᴒᴟᴒᴑͼԜͼᴐꞌ꞉ꜜ꞉ᴐԜꞌꞌᴦͼᴠ꞉Ⱳꜜ꞉ⱱ꞉ᴐԜꜜᴡͼꞌԜԝꜝᴟԜᴡꜝᴟᴦͼԜԝꜜꜝᴟꜛԜꞌ꞉ᴡᴦͼꜝᴟͼⱨⱬ᷅ͼⱷꜜͼᴡⱳᴒͼ
Ԝꜞꜞᴟꜝꜞᴟ꞉Ԝᴡᴒͼꜞⱳᴦᴠ꞉ꜝꞌꜝⱲ꞉ᴐͼᴠᴒᴡᴡ꞉ꜜⱲԓͼᴠᴢᴐⱳͼԜᴠͼⱷᴃͼⱳᴒꜞԜᴟ꞉ꜜͼᴡⱳᴒᴟԜꜞᴦԓͼԜ͟ᴁᴁͼᴐԜꜜͼԝᴒͼᴢᴠᴒᴑͼᴡꜝͼꜛꜝꜜ꞉ᴡꜝᴟͼ
ԝꞌᴒᴒᴑ꞉ꜜⱲͼᴟ꞉ᴠꞋ᷅ͼⱶꜝᴤᴒᴣᴒᴟԓͼԜᴠͼꜜꜝᴡᴒᴑͼ꞉ꜜͼᴡⱳᴒͼⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟᴠͼⱩᴟꜝᴐⱳᴢᴟᴒԓͼԜ͟ᴁᴁͼꜞᴟꜝꞌꜝꜜⱲԜᴡ꞉ꜝꜜͼᴑᴢᴒͼᴡꜝͼ
ꜞꞌԜᴠꜛԜͼꞋԜꞌꞌ꞉Ꞌᴟᴒ꞉ꜜͼ꞉ꜜⱳ꞉ԝ꞉ᴡ꞉ꜝꜜͼ꞉ᴠͼԜꜜͼԜᴟᴡ꞉ⱱԜᴐᴡᴢԜꞌͼin vitro ꜞⱳᴒꜜꜝꜛᴒꜜꜝꜜ᷅ͼⱨꞌᴡⱳꜝᴢⱲⱳͼꜞꞌԜᴠꜛԜͼꞋԜꞌꞌ꞉Ꞌᴟᴒ꞉ꜜͼ
ᴑᴟ꞉ᴣᴒᴠͼⱱ꞉ԝᴟ꞉ꜜͼⱱꜝᴟꜛԜᴡ꞉ꜝꜜͼ꞉ꜜͼᴡⱳᴒͼԜ͟ᴁᴁͼԜᴠᴠԜᴦԓͼꜞꞌԜᴠꜛԜͼꞋԜꞌꞌ꞉Ꞌᴟᴒ꞉ꜜ᷄ᴑᴟ꞉ᴣᴒꜜͼᴐꜝԜⱲᴢꞌԜᴡ꞉ꜝꜜͼᴑꜝᴒᴠͼꜜꜝᴡͼ
ԜꜞꜞᴒԜᴟͼᴡꜝͼⱳԜᴣᴒͼⱳᴒꜛꜝᴠᴡԜᴡ꞉ᴐͼꜝᴟͼꜝᴡⱳᴒᴟͼꜞⱳᴦᴠ꞉ꜝꞌꜝⱲ꞉ᴐԜꞌꞌᴦͼ꞉ꜛꜞꜝᴟᴡԜꜜᴡͼⱱᴢꜜᴐᴡ꞉ꜝꜜᴠͼin vivo᷅ͼⱷᴡͼ꞉ᴠͼᴤᴒꞌꞌͼ
ᴑꜝᴐᴢꜛᴒꜜᴡᴒᴑͼᴡⱳԜᴡԓͼ꞉ꜜͼⱳᴢꜛԜꜜᴠԓͼᴑᴒⱱ꞉ᴐ꞉ᴒꜜᴐᴦͼꜝⱱͼⱱԜᴐᴡꜝᴟͼᴅⱷⱷͼꜝᴟͼꜞᴟᴒꞋԜꞌꞌ꞉Ꞌᴟᴒ꞉ꜜͼӿԜꜜᴑͼᴡⱳᴢᴠͼꜞꞌԜᴠꜛԜͼ
ꞋԜꞌꞌ꞉Ꞌᴟᴒ꞉ꜜԐͼ꞉ᴠͼꜜꜝᴡͼԜᴠᴠꜝᴐ꞉Ԝᴡᴒᴑͼᴤ꞉ᴡⱳͼԜԝꜜꜝᴟꜛԜꞌԝꞌᴒᴒᴑ꞉ꜜⱲԓͼᴒ꞉ᴡⱳᴒᴟͼᴠꜞꜝꜜᴡԜꜜᴒꜝᴢᴠͼꜝᴟͼᴑᴢᴟ꞉ꜜⱲͼᴠᴢᴟⱲ꞉ᴐԜꞌͼ
ꜞᴟꜝᴐᴒᴑᴢᴟᴒᴠͼӿϸᴒꜜꜜᴒͼԜꜜᴑͼⱵᴟᴢԝᴒᴟԓͼ᷉᷇᷈᷉Ԑ᷅ͼⱫᴒᴠꜞ꞉ᴡᴒͼᴡⱳᴒͼꞌԜᴐꞋͼꜝⱱͼᴐꞌ꞉ꜜ꞉ᴐԜꞌͼᴒⱱⱱᴒᴐᴡԓ ᴑᴒⱱ꞉ᴐ꞉ᴒꜜᴐᴦͼꜝⱱͼᴒ꞉ᴡⱳᴒᴟͼ
ꜞᴟꜝᴡᴒ꞉ꜜͼ꞉ᴠͼԜᴠᴠꜝᴐ꞉Ԝᴡᴒᴑͼᴤ꞉ᴡⱳͼꜛԜᴟꞋᴒᴑͼꜞᴟꜝꞌꜝꜜⱲԜᴡ꞉ꜝꜜͼꜝⱱͼᴡⱳᴒͼԜ͟ᴁᴁ᷅ͼ

Ⱬᴅ᷄᷉Ⱡ᷊᷇
ⱪꞌ꞉ꜜ꞉ᴐԜꞌͼᴁᴟ꞉Ԝꞌͼ͟ᴟꜝᴡꜝᴐꜝꞌⱡͼⱫᴅ᷄᷉Ⱡ᷊᷊᷇᷄᷇
ⱨꜛᴒꜜᴑꜛᴒꜜᴡͼ᷊᷅᷇ͼⱴ꞉ꜜԜꞌⱡͼ᷇ⱠͼꜗԜꜜᴢԜᴟᴦ᷉᷇᷈ⅎ
ⱪꜝꜜⱱ꞉ᴑᴒꜜᴡ꞉Ԝꞌ
͟ԜⱲᴒͼ⅍᷊
ⱫᴦԜᴥͼⱪꜝᴟꜞ᷅
6.16.5
Reporting Investigator Safety Observations to the Sponsor
6.16.5.1
Reporting Non-Serious Adverse Events
ⱨꞌꞌͼⱨⱬᴠԓͼᴟᴒⱲԜᴟᴑꞌᴒᴠᴠͼꜝⱱͼᴠᴒᴟ꞉ꜝᴢᴠꜜᴒᴠᴠԓͼᴠᴒᴣᴒᴟ꞉ᴡᴦԓͼꜝᴟͼᴐԜᴢᴠԜꞌͼᴟᴒꞌԜᴡ꞉ꜝꜜᴠⱳ꞉ꜞͼᴡꜝͼⱷꜚ͟ԓͼᴤ꞉ꞌꞌͼԝᴒͼᴟᴒᴐꜝᴟᴑᴒᴑͼꜝꜜͼ
ᴡⱳᴒͼⱨⱬͼꜞԜⱲᴒͼꜝⱱͼᴡⱳᴒͼᴒⱪϸⱴ᷅ͼⱷꜜͼᴡⱳ꞉ᴠͼᴠᴡᴢᴑᴦͼԜꞌꞌͼⱶⱨⱬͼԜᴡᴡԜᴐꞋᴠͼᴟᴒꜞꜝᴟᴡᴒᴑͼԝᴦͼᴡⱳᴒͼᴠᴢԝ꞊ᴒᴐᴡԓͼᴟᴒⱲԜᴟᴑꞌᴒᴠᴠͼꜝⱱͼ
ᴤⱳᴒᴡⱳᴒᴟͼꜝᴟͼꜜꜝᴡͼᴡⱳᴒᴦͼԜᴟᴒͼᴐꜝꜜⱱ꞉ᴟꜛᴒᴑͼԝᴦͼᴡⱳᴒͼⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟԓͼᴤ꞉ꞌꞌͼԝᴒͼᴐԜꜞᴡᴢᴟᴒᴑͼԜᴠͼⱨⱬᴠ᷅
6.16.5.2
Reporting Pregnancies
ⱷⱱͼԜͼⱱᴒꜛԜꞌᴒͼᴠᴢԝ꞊ᴒᴐᴡͼꜝᴟͼᴡⱳᴒͼⱱᴒꜛԜꞌᴒͼꜞԜᴟᴡꜜᴒᴟͼꜝⱱͼԜͼꜛԜꞌᴒͼᴠᴢԝ꞊ᴒᴐᴡͼԝᴒᴐꜝꜛᴒᴠͼꜞᴟᴒⱲꜜԜꜜᴡͼᴑᴢᴟ꞉ꜜⱲͼᴡⱳᴒͼᴐꜝᴢᴟᴠᴒͼꜝⱱͼ
ᴡⱳᴒͼᴠᴡᴢᴑᴦԓͼᴡⱳᴒͼⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟͼꜛᴢᴠᴡͼᴟᴒꜞꜝᴟᴡͼᴡⱳᴒͼꜞᴟᴒⱲꜜԜꜜᴐᴦͼᴡꜝͼᴡⱳᴒͼᴀꜞꜝꜜᴠꜝᴟӾᴠͼ͟ⱳԜᴟꜛԜᴐꜝᴣ꞉Ⱳ꞉ꞌԜꜜᴐᴒͼ
ⱫᴒꜞԜᴟᴡꜛᴒꜜᴡͼᴢᴠ꞉ꜜⱲͼᴡⱳᴒͼPregnancy Reporting Form ᴤ꞉ᴡⱳ꞉ꜜͼ24 hours ꜝⱱͼԝᴒᴐꜝꜛ꞉ꜜⱲͼԜᴤԜᴟᴒͼꜝⱱͼᴡⱳᴒͼ
ᴒᴣᴒꜜᴡ᷅ͼᴁⱳᴒͼⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟͼꜛᴢᴠᴡͼꜝԝᴡԜ꞉ꜜͼᴐꜝꜜᴠᴒꜜᴡͼᴡꜝͼᴐꜝꞌꞌᴒᴐᴡͼꜞᴟᴒⱲꜜԜꜜᴐᴦͼ꞉ꜜⱱꜝᴟꜛԜᴡ꞉ꜝꜜͼӿ꞉ꜜᴐꞌᴢᴑ꞉ꜜⱲͼᴡⱳᴒͼ
ᴠᴡԜᴡᴢᴠͼꜝⱱͼᴡⱳᴒͼꜜᴒᴤԝꜝᴟꜜԓͼ꞉ⱱͼԜꜞꜞꞌ꞉ᴐԜԝꞌᴒԐ᷅
ⱷⱱͼᴠꜝꜛᴒͼꜝⱱͼᴡⱳᴒͼ꞉ꜜⱱꜝᴟꜛԜᴡ꞉ꜝꜜͼᴟᴒꜟᴢ꞉ᴟᴒᴑͼⱱꜝᴟͼᴐꜝꜛꜞꞌᴒᴡ꞉ꜝꜜͼꜝⱱͼᴡⱳᴒͼ͟ᴟᴒⱲꜜԜꜜᴐᴦͼϸᴒꜞꜝᴟᴡ꞉ꜜⱲͼⱴꜝᴟꜛͼ꞉ᴠͼ
ᴢꜜԜᴣԜ꞉ꞌԜԝꞌᴒͼԜᴡͼᴡⱳᴒͼᴡ꞉ꜛᴒͼꜝⱱͼᴡⱳᴒͼ꞉ꜜ꞉ᴡ꞉Ԝꞌͼᴟᴒꜞꜝᴟᴡԓͼⱱꜝꞌꞌꜝᴤ᷄ᴢꜞͼᴟᴒꜞꜝᴟᴡᴠͼᴤ꞉ꞌꞌͼԝᴒͼᴐꜝꜛꜞꞌᴒᴡᴒᴑͼԜꜜᴑͼᴠᴢԝꜛ꞉ᴡᴡᴒᴑͼ
ᴤ꞉ᴡⱳ꞉ꜜͼ᷉᷾ͼⱳꜝᴢᴟᴠͼꜝⱱͼԝᴒᴐꜝꜛ꞉ꜜⱲͼԜᴤԜᴟᴒͼꜝⱱͼᴡⱳᴒͼꜜᴒᴤͼ꞉ꜜⱱꜝᴟꜛԜᴡ꞉ꜝꜜ᷅ͼᴁⱳᴒͼⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟͼ꞉ᴠͼᴟᴒꜟᴢ꞉ᴟᴒᴑͼᴡꜝͼ
ⱱꜝꞌꞌꜝᴤͼᴡⱳᴒͼꜞᴟᴒⱲꜜԜꜜᴐᴦͼᴡⱳᴟꜝᴢⱲⱳͼᴑᴒꞌ꞉ᴣᴒᴟᴦ᷅ͼᴁⱳᴒͼꜝᴢᴡᴐꜝꜛᴒͼꜝⱱͼᴡⱳᴒͼꜞᴟᴒⱲꜜԜꜜᴐᴦͼԜꜜᴑͼᴡⱳᴒͼᴠᴡԜᴡᴢᴠͼꜝⱱͼᴡⱳᴒͼ
ꜜᴒᴤԝꜝᴟꜜͼӿ꞉ⱱͼԜꜞꜞꞌ꞉ᴐԜԝꞌᴒԐͼᴤ꞉ꞌꞌͼԝᴒͼᴟᴒꜞꜝᴟᴡᴒᴑꜝꜜͼᴡⱳᴒͼ͟ᴟᴒⱲꜜԜꜜᴐᴦͼϸᴒꜞꜝᴟᴡ꞉ꜜⱲͼⱴꜝᴟꜛͼᴤ꞉ᴡⱳ꞉ꜜͼ᷉᷾ⱳꜝᴢᴟᴠͼꜝⱱͼ
ԝᴒᴐꜝꜛ꞉ꜜⱲͼԜᴤԜᴟᴒ᷅
6.16.5.3
Safety Observations Requiring Expedited Reporting by the Investigator to the 
Sponsor
ⱨꜜᴦͼꜝᴐᴐᴢᴟᴟᴒꜜᴐᴒͼꜝⱱͼᴡⱳᴒͼⱱꜝꞌꞌꜝᴤ꞉ꜜⱲͼᴒᴣᴒꜜᴡᴠͼꜝᴟͼꜝᴢᴡᴐꜝꜛᴒᴠͼ꞉ꜜͼԜͼᴠᴢԝ꞊ᴒᴐᴡͼ꞉ꜜͼᴡⱳᴒͼᴡᴟ꞉Ԝꞌͼꜛᴢᴠᴡͼԝᴒͼᴟᴒꜞꜝᴟᴡᴒᴑͼ
ᴒᴥꜞᴒᴑ꞉ᴡ꞉ꜝᴢᴠꞌᴦͼԝᴦͼᴡⱳᴒͼⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟͼꜝᴟͼꜟᴢԜꞌ꞉ⱱ꞉ᴒᴑͼᴑᴒᴠ꞉ⱲꜜᴒᴒͼᴡꜝͼᴡⱳᴒͼᴀꜞꜝꜜᴠꜝᴟӾᴠͼ͟ⱳԜᴟꜛԜᴐꜝᴣ꞉Ⱳ꞉ꞌԜꜜᴐᴒͼ
ⱫᴒꜞԜᴟᴡꜛᴒꜜᴡⱡ
ᶄ
ᴀⱨⱬ
ᶄ
ⱨⱬᴀⱷ
ᶄ
꜡ᴣᴒᴟᴑꜝᴠᴒ
ᶄ
ⱪԜꜜᴐᴒᴟ
ᴁⱳᴒͼⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟͼ꞉ᴠͼᴡꜝͼᴟᴒꜞꜝᴟᴡͼԜꜜᴦͼᴒᴥꜞᴒᴑ꞉ᴡᴒᴑͼᴠԜⱱᴒᴡᴦͼꜝԝᴠᴒᴟᴣԜᴡ꞉ꜝꜜᴠͼⱱᴟꜝꜛͼᴡⱳᴒͼꞌ꞉ᴠᴡͼԜԝꜝᴣᴒͼᴡꜝͼᴡⱳᴒͼᴀꜞꜝꜜᴠꜝᴟͼ
ᴢᴠ꞉ꜜⱲͼᴡⱳᴒͼSAE Reporting Form in the EDC system ᴤ꞉ᴡⱳ꞉ꜜͼ᷉᷾ͼⱳꜝᴢᴟᴠꜝⱱͼԝᴒᴐꜝꜛ꞉ꜜⱲͼԜᴤԜᴟᴒͼꜝⱱͼᴡⱳᴒͼ
ᴒᴣᴒꜜᴡ᷅
ⱨꜜᴦͼᴀⱨⱬͼᴟᴒꜞꜝᴟᴡᴒᴑͼᴡꜝͼᴡⱳᴒͼᴀꜞꜝꜜᴠꜝᴟͼ͟ⱳԜᴟꜛԜᴐꜝᴣ꞉Ⱳ꞉ꞌԜꜜᴐᴒͼⱫᴒꜞԜᴟᴡꜛᴒꜜᴡͼᴢᴠ꞉ꜜⱲͼᴡⱳᴒͼᴀⱨⱬͼϸᴒꜞꜝᴟᴡ꞉ꜜⱲͼ
ⱴꜝᴟꜛͼ꞉ꜜͼᴡⱳᴒͼⱬⱫⱪͼᴠᴦᴠᴡᴒꜛͼ꞉ᴠͼᴡꜝͼԝᴒͼᴟᴒᴐꜝᴟᴑᴒᴑͼ꞉ꜜͼᴡⱳᴒͼᴒⱪϸⱴԓͼԜᴠͼᴤᴒꞌꞌͼԜᴠͼ꞉ꜜͼᴡⱳᴒͼᴠᴢԝ꞊ᴒᴐᴡӾᴠͼᴠꜝᴢᴟᴐᴒͼ
ᴑꜝᴐᴢꜛᴒꜜᴡԜᴡ꞉ꜝꜜͼԜꞌꜝꜜⱲͼᴤ꞉ᴡⱳͼԜꜜᴦͼԜᴐᴡ꞉ꜝꜜᴠͼᴡԜꞋᴒꜜ᷅ͼⱷⱱͼԜꞌꞌͼᴟᴒꜟᴢ꞉ᴟᴒᴑͼ꞉ꜜⱱꜝᴟꜛԜᴡ꞉ꜝꜜͼꜝꜜͼᴡⱳᴒͼⱱꜝᴟꜛͼ꞉ᴠͼꜜꜝᴡͼ
ԜᴣԜ꞉ꞌԜԝꞌᴒͼԜᴡͼᴡⱳᴒͼᴡ꞉ꜛᴒͼꜝⱱͼᴡⱳᴒͼ꞉ꜜ꞉ᴡ꞉Ԝꞌͼᴟᴒꜞꜝᴟᴡԓͼⱱꜝꞌꞌꜝᴤ᷄ᴢꜞͼ꞉ꜜⱱꜝᴟꜛԜᴡ꞉ꜝꜜͼᴤ꞉ꞌꞌͼԝᴒͼᴐꜝꜛꜞꞌᴒᴡᴒᴑͼ꞉ꜜͼᴡⱳᴒͼⱬⱫⱪͼ
ᴠᴦᴠᴡᴒꜛ᷅

Ⱬᴅ᷄᷉Ⱡ᷊᷇
ⱪꞌ꞉ꜜ꞉ᴐԜꞌͼᴁᴟ꞉Ԝꞌͼ͟ᴟꜝᴡꜝᴐꜝꞌⱡͼⱫᴅ᷄᷉Ⱡ᷊᷊᷇᷄᷇
ⱨꜛᴒꜜᴑꜛᴒꜜᴡͼ᷊᷅᷇ͼⱴ꞉ꜜԜꞌⱡͼ᷇ⱠͼꜗԜꜜᴢԜᴟᴦ᷉᷇᷈ⅎ
ⱪꜝꜜⱱ꞉ᴑᴒꜜᴡ꞉Ԝꞌ
͟ԜⱲᴒͼ⅍᷾
ⱫᴦԜᴥͼⱪꜝᴟꜞ᷅
ᴁⱳᴒͼⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟͼ꞉ᴠͼᴟᴒꜟᴢ꞉ᴟᴒᴑͼᴡꜝͼⱱꜝꞌꞌꜝᴤͼᴀⱨⱬᴠͼᴢꜜᴡ꞉ꞌͼᴟᴒᴠꜝꞌᴢᴡ꞉ꜝꜜͼᴟᴒⱲԜᴟᴑꞌᴒᴠᴠͼꜝⱱͼᴤⱳᴒᴡⱳᴒᴟͼᴡⱳᴒͼᴠᴢԝ꞊ᴒᴐᴡᴠͼ
Ԝᴟᴒͼᴠᴡ꞉ꞌꞌͼꜞԜᴟᴡ꞉ᴐ꞉ꜞԜᴡ꞉ꜜⱲͼ꞉ꜜͼᴡⱳᴒͼᴠᴡᴢᴑᴦ᷅ͼᴀⱨⱬͼᴟᴒᴠꜝꞌᴢᴡ꞉ꜝꜜͼ꞉ᴠͼᴑᴒⱱ꞉ꜜᴒᴑͼԜᴠⱡ
ᶄ
ϸᴒᴠꜝꞌᴣᴒᴑͼᴤ꞉ᴡⱳͼꜝᴟͼᴤ꞉ᴡⱳꜝᴢᴡͼᴟᴒᴠ꞉ᴑᴢԜꞌͼᴒⱱⱱᴒᴐᴡᴠ᷅
ᶄ
ⱨͼᴟᴒᴡᴢᴟꜜͼᴡꜝͼԝԜᴠᴒꞌ꞉ꜜᴒͼⱱꜝᴟͼԜͼꜞᴟᴒ᷄ᴒᴥ꞉ᴠᴡ꞉ꜜⱲͼᴐꜝꜜᴑ꞉ᴡ꞉ꜝꜜ᷅
ᶄ
ꜙԜԝꜝᴟԜᴡꜝᴟᴦͼᴣԜꞌᴢᴒᴠͼⱳԜᴣᴒͼᴟᴒᴡᴢᴟꜜᴒᴑͼᴡꜝͼԝԜᴠᴒꞌ꞉ꜜᴒͼꜝᴟͼᴠᴡԜԝ꞉ꞌ꞉ᴧᴒᴑ᷅
ᶄ
ᴁⱳᴒͼⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟͼᴑꜝᴒᴠͼꜜꜝᴡͼᴒᴥꜞᴒᴐᴡͼԜꜜᴦͼⱱᴢᴟᴡⱳᴒᴟͼ꞉ꜛꜞᴟꜝᴣᴒꜛᴒꜜᴡͼꜝᴟͼᴤꜝᴟᴠᴒꜜ꞉ꜜⱲͼꜝⱱͼᴡⱳᴒͼᴒᴣᴒꜜᴡ᷅
ᶄ
ⱴԜᴡԜꞌͼꜝᴢᴡᴐꜝꜛᴒᶯ꞉ⱱͼԜꜜͼԜᴢᴡꜝꜞᴠᴦͼ꞉ᴠͼꜞᴒᴟⱱꜝᴟꜛᴒᴑԓͼᴡⱳᴒͼԜᴢᴡꜝꜞᴠᴦͼᴟᴒꜞꜝᴟᴡͼ꞉ᴠͼᴟᴒꜟᴢᴒᴠᴡᴒᴑͼᴡꜝͼԝᴒͼꜞᴟꜝᴣ꞉ᴑᴒᴑͼᴡꜝͼ
ᴡⱳᴒͼᴠꜞꜝꜜᴠꜝᴟͼԜᴠͼᴠꜝꜝꜜͼԜᴠͼ꞉ᴡͼ꞉ᴠͼԜᴣԜ꞉ꞌԜԝꞌᴒ᷅
6.16.5.4
Expedited Reporting by the Sponsor to a Regulatory Health Authority
ᴁⱳᴒͼᴀꜞꜝꜜᴠꜝᴟͼꜝᴟͼᴑᴒᴠ꞉Ⱳꜜᴒᴒͼᴤ꞉ꞌꞌͼᴟᴒꜞꜝᴟᴡͼᴟᴒꞌᴒᴣԜꜜᴡͼᴠԜⱱᴒᴡᴦͼ꞉ꜜⱱꜝᴟꜛԜᴡ꞉ꜝꜜͼᴡꜝͼᴐꜝꜜᴐᴒᴟꜜᴒᴑͼⱳᴒԜꞌᴡⱳͼԜᴢᴡⱳꜝᴟ꞉ᴡ꞉ᴒᴠͼ
꞉ꜜͼԜᴐᴐꜝᴟᴑԜꜜᴐᴒͼᴤ꞉ᴡⱳͼꞌꜝᴐԜꞌͼꞌԜᴤᴠͼԜꜜᴑͼᴟᴒⱲᴢꞌԜᴡ꞉ꜝꜜᴠ᷅
6.16.5.5
Safety Contact Information 
24-Hour Medical Safety Contact for US, Canada, Europe, and Middle East
Sponsor Pharmacovigilance Department
ⱬꜛԜ꞉ꞌⱡͼ
͟ⱳꜝꜜᴒͼӿᴂᴀԐⱡͼ
6.16.5.6
Safety Notifications by the Sponsor to the Investigator
ⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟᴠͼᴤ꞉ꞌꞌͼᴟᴒᴐᴒ꞉ᴣᴒͼꜞᴟꜝꜛꜞᴡͼꜜꜝᴡ꞉ⱱ꞉ᴐԜᴡ꞉ꜝꜜͼꜝⱱͼԜꜜᴦͼԜᴑᴣᴒᴟᴠᴒͼᴒᴥꜞᴒᴟ꞉ᴒꜜᴐᴒͼᴟᴒꞌԜᴡᴒᴑͼᴡꜝͼⱷꜚ͟ͼᴡⱳԜᴡͼ꞉ᴠͼ
ԝꜝᴡⱳͼᴠᴒᴟ꞉ꜝᴢᴠͼԜꜜᴑͼᴢꜜᴒᴥꜞᴒᴐᴡᴒᴑԓͼꜝᴟͼԜꜜᴦͼⱱ꞉ꜜᴑ꞉ꜜⱲͼᴡⱳԜᴡͼᴠᴢⱲⱲᴒᴠᴡᴠͼԜͼᴠ꞉Ⱳꜜ꞉ⱱ꞉ᴐԜꜜᴡͼᴟ꞉ᴠꞋͼⱱꜝᴟͼᴠᴢԝ꞊ᴒᴐᴡᴠ᷅ͼᴁⱳᴒͼ
ⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟͼᴤ꞉ꞌꞌͼꜞᴟꜝꜛꜞᴡꞌᴦͼ꞉ꜜⱱꜝᴟꜛͼⱳ꞉ᴠ᷆ⱳᴒᴟͼⱷϸⱩ᷆ϸⱬⱩ᷆ⱷⱬⱪͼꜝⱱͼᴡⱳᴒͼꜜꜝᴡ꞉ⱱ꞉ᴐԜᴡ꞉ꜝꜜͼԜꜜᴑͼ꞉ꜜᴠᴒᴟᴡͼᴡⱳᴒͼ
ꜜꜝᴡ꞉ⱱ꞉ᴐԜᴡ꞉ꜝꜜͼ꞉ꜜͼᴡⱳᴒͼⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟᶳᴠͼϸᴒⱲᴢꞌԜᴡꜝᴟᴦͼⱩ꞉ꜜᴑᴒᴟͼ꞉ꜜͼԜᴐᴐꜝᴟᴑԜꜜᴐᴒͼᴤ꞉ᴡⱳͼꞌꜝᴐԜꞌͼᴟᴒⱲᴢꞌԜᴡ꞉ꜝꜜᴠ᷅ͼ
6.16.5.7
Unblinding a Subject’s Treatment during the Trial
ϸᴒꜟᴢ꞉ᴟᴒꜛᴒꜜᴡᴠͼⱱꜝᴟͼᴒꜛᴒᴟⱲᴒꜜᴐᴦͼᴢꜜԝꞌ꞉ꜜᴑ꞉ꜜⱲͼԝᴦͼᴡⱳᴒͼⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟͼԜᴟᴒͼᴑᴒᴡԜ꞉ꞌᴒᴑͼ꞉ꜜͼᴀᴒᴐᴡ꞉ꜝꜜͼ᷿᷅᷾᷅ͼᴁꜝͼԜᴠᴠᴒᴠᴠͼ
ԜꜜͼꜝᴐᴐᴢᴟᴟᴒꜜᴐᴒͼꜝⱱͼԜͼᴠԜⱱᴒᴡᴦͼꜝԝᴠᴒᴟᴣԜᴡ꞉ꜝꜜԓͼᴡⱳᴒͼᴀꜞꜝꜜᴠꜝᴟ͟ⱳԜᴟꜛԜᴐꜝᴣ꞉Ⱳ꞉ꞌԜꜜᴐᴒͼⱫᴒꜞԜᴟᴡꜛᴒꜜᴡͼꜛԜᴦͼᴢꜜԝꞌ꞉ꜜᴑͼ
ᴡⱳᴒͼᴡᴟᴒԜᴡꜛᴒꜜᴡͼꜝⱱͼԜꜜᴦͼᴠᴢԝ꞊ᴒᴐᴡ᷅
6.17
Subject Withdrawal
ᴁⱳᴒͼⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟͼꜛԜᴦͼᴤ꞉ᴡⱳᴑᴟԜᴤͼԜͼᴠᴢԝ꞊ᴒᴐᴡͼⱱᴟꜝꜛͼᴡᴟᴒԜᴡꜛᴒꜜᴡͼᴤ꞉ᴡⱳͼᴠᴡᴢᴑᴦͼᴑᴟᴢⱲͼⱱꜝᴟͼԜꜜᴦͼꜝⱱͼᴡⱳᴒͼᴟᴒԜᴠꜝꜜᴠͼ
ꞌ꞉ᴠᴡᴒᴑͼԝᴒꞌꜝᴤ᷅ͼ
ᶄ
ⱷꜜͼᴡⱳᴒͼꜝꜞ꞉ꜜ꞉ꜝꜜͼꜝⱱͼᴡⱳᴒͼⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟԓͼᴡⱳᴒͼᴠᴢԝ꞊ᴒᴐᴡͼ꞉ᴠͼᴢꜜԜԝꞌᴒͼᴡꜝͼᴐꜝꜛꜞꞌᴦͼᴤ꞉ᴡⱳͼᴡⱳᴒͼᴟᴒꜟᴢ꞉ᴟᴒꜛᴒꜜᴡᴠͼꜝⱱͼ
ᴡⱳᴒͼꜞᴟꜝᴡꜝᴐꜝꞌͼⱱꜝᴟͼᴠԜᴡ꞉ᴠⱱԜᴐᴡꜝᴟᴦͼᴐꜝꜛꜞꞌᴒᴡ꞉ꜝꜜͼꜝᴟͼ꞉ꜜᴡᴒᴟꜞᴟᴒᴡԜᴡ꞉ꜝꜜͼꜝⱱͼᴠᴡᴢᴑᴦͼᴟᴒᴠᴢꞌᴡᴠͼӿ꞉ꜜᴐꞌᴢᴑ꞉ꜜⱲͼᴢᴠᴒͼꜝⱱͼ
ꜞᴟꜝⱳ꞉ԝ꞉ᴡ꞉ᴣᴒͼꜛᴒᴑ꞉ᴐԜᴡ꞉ꜝꜜᴠԐԓ
PPD
PPD

Ⱬᴅ᷄᷉Ⱡ᷊᷇
ⱪꞌ꞉ꜜ꞉ᴐԜꞌͼᴁᴟ꞉Ԝꞌͼ͟ᴟꜝᴡꜝᴐꜝꞌⱡͼⱫᴅ᷄᷉Ⱡ᷊᷊᷇᷄᷇
ⱨꜛᴒꜜᴑꜛᴒꜜᴡͼ᷊᷅᷇ͼⱴ꞉ꜜԜꞌⱡͼ᷇ⱠͼꜗԜꜜᴢԜᴟᴦ᷉᷇᷈ⅎ
ⱪꜝꜜⱱ꞉ᴑᴒꜜᴡ꞉Ԝꞌ
͟ԜⱲᴒͼ⅍᷿
ⱫᴦԜᴥͼⱪꜝᴟꜞ᷅
ᶄ
ⱨͼᴠᴒᴟ꞉ꜝᴢᴠͼꜝᴟͼ꞉ꜜᴡꜝꞌᴒᴟԜԝꞌᴒͼⱨⱬͼꜝᴐᴐᴢᴟᴠԓ
ᶄ
ⱨͼᴐꞌ꞉ꜜ꞉ᴐԜꞌꞌᴦͼᴠ꞉Ⱳꜜ꞉ⱱ꞉ᴐԜꜜᴡͼᴐⱳԜꜜⱲᴒͼ꞉ꜜͼԜͼꞌԜԝꜝᴟԜᴡꜝᴟᴦͼꜞԜᴟԜꜛᴒᴡᴒᴟͼꜝᴐᴐᴢᴟᴠԓ
ᶄ
ᴁⱳᴒͼᴀꜞꜝꜜᴠꜝᴟͼꜝᴟͼⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟͼᴡᴒᴟꜛ꞉ꜜԜᴡᴒᴠͼᴡⱳᴒͼᴠᴡᴢᴑᴦԓͼꜝᴟ
ᶄ
ᴁⱳᴒͼᴠᴢԝ꞊ᴒᴐᴡͼᴟᴒꜟᴢᴒᴠᴡᴠͼᴡꜝͼԝᴒͼᴑ꞉ᴠᴐꜝꜜᴡ꞉ꜜᴢᴒᴑͼⱱᴟꜝꜛͼᴡⱳᴒͼᴠᴡᴢᴑᴦ᷅
ᴀᴢԝ꞊ᴒᴐᴡᴠͼᴤ꞉ꞌꞌͼᴐꜝꜜᴡ꞉ꜜᴢᴒͼᴡꜝͼԝᴒͼⱱꜝꞌꞌꜝᴤᴒᴑͼᴡⱳᴟꜝᴢⱲⱳͼᴐꜝꜛꜞꞌᴒᴡ꞉ꜝꜜͼꜝⱱͼԜꞌꞌͼᴠᴐⱳᴒᴑᴢꞌᴒᴑͼᴣ꞉ᴠ꞉ᴡᴠԓͼᴢꜜꞌᴒᴠᴠͼᴡⱳᴒͼ
ᴠᴢԝ꞊ᴒᴐᴡͼᴟᴒꜟᴢᴒᴠᴡᴠͼᴡꜝͼԝᴒͼᴑ꞉ᴠᴐꜝꜜᴡ꞉ꜜᴢᴒᴑͼⱱᴟꜝꜛͼᴡⱳᴒͼᴠᴡᴢᴑᴦ᷅ͼᴁⱳᴒͼᴐᴟ꞉ᴡᴒᴟ꞉ԜͼᴢᴠᴒᴑͼԝᴦͼᴡⱳᴒͼⱫᴀꜚⱩͼᴟᴒⱲԜᴟᴑ꞉ꜜⱲͼ
ᴑꜝᴠᴒͼԜᴑꜛ꞉ꜜ꞉ᴠᴡᴟԜᴡ꞉ꜝꜜͼᴠᴢᴠꜞᴒꜜᴠ꞉ꜝꜜͼԜꜜᴑ᷆ꜝᴟͼᴠᴡᴢᴑᴦͼᴑ꞉ᴠᴐꜝꜜᴡ꞉ꜜᴢԜᴡ꞉ꜝꜜͼԜᴟᴒͼꜞᴟꜝᴣ꞉ᴑᴒᴑͼ꞉ꜜͼᴀᴒᴐᴡ꞉ꜝꜜͼ᷊᷅᷈᷅᷉᷅
6.18
Appropriateness of Measurements
ᴁⱳ꞉ᴠͼ꞉ᴠͼԜͼ͟ⱳԜᴠᴒͼ᷊ͼꜛᴢꞌᴡ꞉᷄ᴐᴒꜜᴡᴒᴟԓͼᴟԜꜜᴑꜝꜛ꞉ᴧᴒᴑԓͼᴑꜝᴢԝꞌᴒ᷄ԝꞌ꞉ꜜᴑԓͼꜞꞌԜᴐᴒԝꜝ᷄ᴐꜝꜜᴡᴟꜝꞌꞌᴒᴑͼᴠᴡᴢᴑᴦͼᴡⱳԜᴡͼ꞉ᴠͼ
ᴑᴒᴠ꞉ⱲꜜᴒᴑͼᴡꜝͼᴒᴣԜꞌᴢԜᴡᴒͼᴡⱳᴒͼᴒⱱⱱ꞉ᴐԜᴐᴦͼԜꜜᴑͼᴠԜⱱᴒᴡᴦͼꜝⱱͼⱫᴅ᷄᷉Ⱡ᷊᷇ͼ꞉ꜜͼꜞᴟᴒᴣᴒꜜᴡ꞉ꜝꜜͼꜝⱱͼⱶⱨⱬͼԜᴡᴡԜᴐꞋᴠͼ꞉ꜜͼ
ᴠᴢԝ꞊ᴒᴐᴡᴠͼᴤ꞉ᴡⱳͼⱶⱨⱬ᷅ͼⱫᴅ᷄᷉Ⱡ᷊᷇ͼ꞉ᴠͼԜͼᴟᴒᴐꜝꜛԝ꞉ꜜԜꜜᴡԓͼⱱᴢꞌꞌᴦͼⱳᴢꜛԜꜜͼⱷⱲⱵ᷈ԓͼꞋԜꜞꜞԜͼꞌ꞉ⱲⱳᴡͼᴐⱳԜ꞉ꜜԓͼꜛꜝꜜꜝᴐꞌꜝꜜԜꞌͼ
Ԝꜜᴡ꞉ԝꜝᴑᴦ᷅ͼᴁⱳᴒͼᴟԜꜜᴑꜝꜛ꞉ᴧᴒᴑԓͼꜞꞌԜᴐᴒԝꜝͼᴐꜝꜜᴡᴟꜝꞌꞌᴒᴑͼᴠᴡᴢᴑᴦͼᴑᴒᴠ꞉Ⱳꜜͼ꞉ᴠͼԜͼᴠᴡԜꜜᴑԜᴟᴑͼԜꜞꜞᴟꜝԜᴐⱳͼⱱꜝᴟͼ
ᴑ꞉ⱱⱱᴒᴟᴒꜜᴡ꞉Ԝᴡ꞉ꜝꜜͼԝᴒᴡᴤᴒᴒꜜͼᴡⱳᴒͼᴒⱱⱱ꞉ᴐԜᴐᴦͼԜꜜᴑͼᴠԜⱱᴒᴡᴦͼꜞᴟꜝⱱ꞉ꞌᴒᴠͼꜝⱱͼԜꜜͼԜᴐᴡ꞉ᴣᴒͼԜꜜᴑͼꜞꞌԜᴐᴒԝꜝͼᴡᴟᴒԜᴡꜛᴒꜜᴡͼᴤⱳᴒꜜͼ
Ԝᴑꜛ꞉ꜜ꞉ᴠᴡᴒᴟᴒᴑͼᴡꜝͼᴠᴢԝ꞊ᴒᴐᴡᴠ᷅ͼⱨꞌꞌͼꜝⱱͼᴡⱳᴒͼꜛᴒԜᴠᴢᴟᴒᴠͼᴒꜛꜞꞌꜝᴦᴒᴑͼ꞉ꜜͼᴡⱳ꞉ᴠͼꜞᴟꜝᴡꜝᴐꜝꞌͼԜᴟᴒͼᴠᴡԜꜜᴑԜᴟᴑͼꜛᴒԜᴠᴢᴟᴒᴠͼ
ᴟꜝᴢᴡ꞉ꜜᴒꞌᴦͼᴢᴠᴒᴑͼⱱꜝᴟͼᴡⱳᴒͼᴒᴣԜꞌᴢԜᴡ꞉ꜝꜜͼꜝⱱͼᴡⱳᴒͼᴒⱱⱱ꞉ᴐԜᴐᴦԓͼᴠԜⱱᴒᴡᴦͼԜꜜᴑͼᴡꜝꞌᴒᴟԜԝ꞉ꞌ꞉ᴡᴦͼꜝⱱͼԜꜜͼ꞉ꜜᴣᴒᴠᴡ꞉ⱲԜᴡ꞉ꜝꜜԜꞌͼ
ꜞᴟꜝᴑᴢᴐᴡ᷅

Ⱬᴅ᷄᷉Ⱡ᷊᷇
ⱪꞌ꞉ꜜ꞉ᴐԜꞌͼᴁᴟ꞉Ԝꞌͼ͟ᴟꜝᴡꜝᴐꜝꞌⱡͼⱫᴅ᷄᷉Ⱡ᷊᷊᷇᷄᷇
ⱨꜛᴒꜜᴑꜛᴒꜜᴡͼ᷊᷅᷇ͼⱴ꞉ꜜԜꞌⱡͼ᷇ⱠͼꜗԜꜜᴢԜᴟᴦ᷉᷇᷈ⅎ
ⱪꜝꜜⱱ꞉ᴑᴒꜜᴡ꞉Ԝꞌ
͟ԜⱲᴒͼ⅍⅍
ⱫᴦԜᴥͼⱪꜝᴟꜞ᷅
7
STUDY ACTIVITIES
ᴀᴡᴢᴑᴦͼԜᴐᴡ꞉ᴣ꞉ᴡ꞉ᴒᴠͼԜᴟᴒͼᴠᴢꜛꜛԜᴟ꞉ᴧᴒᴑͼԝᴦͼᴠᴡᴢᴑᴦͼᴣ꞉ᴠ꞉ᴡͼ꞉ꜜͼᴁԜԝꞌᴒͼ᷈ӿᴀᴡᴢᴑᴦͼⱨᴐᴡ꞉ᴣ꞉ᴡ꞉ᴒᴠͼᴀᴐⱳᴒᴑᴢꞌᴒԐ᷅
7.1
Screening 
The following procedures and assessments are to be performed during Screening:
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ⱷꜜⱱꜝᴟꜛᴒᴑͼᴐꜝꜜᴠᴒꜜᴡͼӿᴀᴒᴐᴡ꞉ꜝꜜͼ⅍᷅᷈Ԑ
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ⱬꞌ꞉Ⱳ꞉ԝ꞉ꞌ꞉ᴡᴦͼᴟᴒᴣ꞉ᴒᴤͼӿᴀᴒᴐᴡ꞉ꜝꜜͼ⅍᷅᷉Ԑ
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ⱫᴒꜛꜝⱲᴟԜꜞⱳ꞉ᴐᴠͼԜꜜᴑͼꜛᴒᴑ꞉ᴐԜꞌͼⱳ꞉ᴠᴡꜝᴟᴦͼӿᴀᴒᴐᴡ꞉ꜝꜜͼ⅍᷊᷅Ԑ
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ⱪ᷈᷄ⱷ꜠ⱶͼⱱᴢꜜᴐᴡ꞉ꜝꜜԜꞌͼԜᴠᴠԜᴦԓͼⱪ᷾ͼԜꜜᴑͼⱪ᷈ꜟͼᴠԜꜛꜞꞌᴒͼᴐꜝꞌꞌᴒᴐᴡ꞉ꜝꜜͼӿᴀᴒᴐᴡ꞉ꜝꜜͼ⅍᷅˲Ԑ
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͟ᴟᴒⱲꜜԜꜜᴐᴦͼᴡᴒᴠᴡԓͼᴠᴒᴟᴢꜛͼꜝᴟͼᴢᴟ꞉ꜜᴒͼӿⱱᴒꜛԜꞌᴒᴠԐͼӿᴀᴒᴐᴡ꞉ꜝꜜͼ⅍᷅˲Ԑ
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ᴃ꞉ᴡԜꞌͼᴠ꞉Ⱳꜜᴠͼ꞉ꜜᴐꞌᴢᴑ꞉ꜜⱲͼԝꜝᴑᴦͼᴡᴒꜛꜞᴒᴟԜᴡᴢᴟᴒԓͼⱶϸԓͼⱩ͟ͼԜꜜᴑͼϸϸͼӿᴀᴒᴐᴡ꞉ꜝꜜ⅍᷿᷅Ԑ
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ⱪꜝꜛꜞꞌᴒᴡᴒͼꜞⱳᴦᴠ꞉ᴐԜꞌͼᴒᴥԜꜛ꞉ꜜԜᴡ꞉ꜝꜜͼӿᴀᴒᴐᴡ꞉ꜝꜜͼ⅍᷅⅍ԐⱢͼᴑꜝᴐᴢꜛᴒꜜᴡԜᴡ꞉ꜝꜜͼꜝⱱͼⱳᴒ꞉ⱲⱳᴡͼԜꜜᴑͼᴤᴒ꞉Ⱳⱳᴡ
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᷈᷉᷄ꜙᴒԜᴑͼⱬⱪⱵͼӿᴀᴒᴐᴡ꞉ꜝꜜͼ⅍᷅ⅎԐ
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ꜙԜԝꜝᴟԜᴡꜝᴟᴦͼᴡᴒᴠᴡ꞉ꜜⱲͼ꞉ꜜᴐꞌᴢᴑ꞉ꜜⱲԓͼᴠᴒᴟꜝꞌꜝⱲᴦԓͼⱳᴒꜛԜᴡꜝꞌꜝⱲᴦԓͼᴐꜝԜⱲᴢꞌԜᴡ꞉ꜝꜜԓͼᴠᴒᴟᴢꜛͼᴐⱳᴒꜛ꞉ᴠᴡᴟᴦͼԜꜜᴑͼ
ᴢᴟ꞉ꜜԜꞌᴦᴠ꞉ᴠͼӿᴀᴒᴐᴡ꞉ꜝꜜͼ⅍᷅˲Ԑ
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͟ᴟ꞉ꜝᴟͼԜꜜᴑͼᴐꜝꜜᴐꜝꜛ꞉ᴡԜꜜᴡͼᴡⱳᴒᴟԜꜞᴦͼӿᴀᴒᴐᴡ꞉ꜝꜜͼ⅍᷅᷈᷉Ԑ
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ⱶⱨⱬͼԜᴡᴡԜᴐꞋͼ꞉ꜜⱱꜝᴟꜛԜᴡ꞉ꜝꜜͼӿᴀᴒᴐᴡ꞉ꜝꜜͼ⅍᷅᷾Ԑ
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ⱨⱬͼᴐꜝꞌꞌᴒᴐᴡ꞉ꜝꜜͼӿᴀᴒᴐᴡ꞉ꜝꜜͼ⅍᷅᷈⅍ԐⱢͼꜞᴟᴒ᷄ᴒᴥ꞉ᴠᴡ꞉ꜜⱲͼᴠ꞉ⱲꜜᴠͼԜꜜᴑͼᴠᴦꜛꜞᴡꜝꜛᴠ
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ᴀᴢԝ꞊ᴒᴐᴡᴠͼᴤⱳꜝͼԜᴟᴒͼꜝꜜͼꜙᴁ͟ͼⱱꜝᴟͼⱶⱨⱬͼꜛᴢᴠᴡͼᴐꜝꜛꜞꞌᴒᴡᴒͼԜͼ᷉ͼᴤᴒᴒꞋͼᴤԜᴠⱳꜝᴢᴡͼꜞᴒᴟ꞉ꜝᴑԓͼԜᴠͼᴐꜝꜜⱱ꞉ᴟꜛᴒᴑͼԝᴦͼ
ᴡⱳᴒͼⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟԓͼԝᴒⱱꜝᴟᴒͼᴒꜜᴡᴒᴟ꞉ꜜⱲͼᴡⱳᴒͼᴟᴢꜜ᷄꞉ꜜͼꜞᴒᴟ꞉ꜝᴑ᷅
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ꜙᴁ͟ͼᴤԜᴠⱳꜝᴢᴡͼ꞉ᴠͼꜞᴒᴟꜛ꞉ᴡᴡᴒᴑͼԜᴠͼꞌꜝꜜⱲͼԜᴠͼᴡⱳᴒͼⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟͼᴑᴒᴡᴒᴟꜛ꞉ꜜᴒᴠͼᴡⱳԜᴡͼᴑꜝ꞉ꜜⱲͼᴠꜝͼᴤꜝᴢꞌᴑͼꜜꜝᴡͼ
ꜞꞌԜᴐᴒͼᴡⱳᴒͼᴠᴢԝ꞊ᴒᴐᴡͼԜᴡͼԜꜜᴦͼᴢꜜᴑᴢᴒͼᴠԜⱱᴒᴡᴦͼᴟ꞉ᴠꞋͼԜꜜᴑͼᴡⱳᴒͼᴠᴢԝ꞊ᴒᴐᴡͼ꞉ᴠͼԜᴡͼꞌᴒԜᴠᴡͼ᷈˲ͼᴦᴒԜᴟᴠͼꜝⱱͼԜⱲᴒ᷅
7.2
Run-in Period 
ᴀᴢԝ꞊ᴒᴐᴡᴠͼᴤⱳꜝͼᴤᴒᴟᴒͼꜝꜜͼꜙᴁ͟ͼꜛԜᴦͼᴒꜜᴡᴒᴟͼᴟᴢꜜ᷄꞉ꜜͼԜⱱᴡᴒᴟͼᴠᴢᴐᴐᴒᴠᴠⱱᴢꞌꞌᴦͼᴐꜝꜛꜞꞌᴒᴡ꞉ꜜⱲͼԜͼ᷉ͼᴤᴒᴒꞋͼᴤԜᴠⱳꜝᴢᴡͼꜝⱱͼ
ᴡⱳᴒ꞉ᴟͼꜙᴁ᷅͟ͼⱨꞌꞌͼᴠᴢԝ꞊ᴒᴐᴡᴠͼᴤ꞉ꞌꞌͼᴢꜜᴑᴒᴟⱲꜝͼԜͼᴟᴢꜜ᷄꞉ꜜͼꜞᴒᴟ꞉ꜝᴑͼꜝⱱͼ᷾ͼᴤᴒᴒꞋᴠͼᴡꜝͼᴑᴒᴡᴒᴟꜛ꞉ꜜᴒͼᴡⱳᴒͼԝԜᴠᴒꞌ꞉ꜜᴒͼⱶⱨⱬͼ
ԜᴡᴡԜᴐꞋͼᴟԜᴡᴒͼӿᴀᴒᴐᴡ꞉ꜝꜜͼ⅍᷅᷾Ԑ᷅ͼᴁⱳᴒͼᴟᴢꜜ᷄꞉ꜜͼꜞᴒᴟ꞉ꜝᴑͼꜛԜᴦͼԝᴒͼᴠⱳꜝᴟᴡᴒꜜᴒᴑͼᴡꜝͼꞌᴒᴠᴠͼᴡⱳԜꜜͼ᷾ͼᴤᴒᴒꞋᴠͼⱱꜝᴟͼԜꜜᴦͼᴠᴢԝ꞊ᴒᴐᴡͼ
ᴤⱳꜝͼᴒᴥꜞᴒᴟ꞉ᴒꜜᴐᴒᴠͼ᷊ͼⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟ᷄ᴐꜝꜜⱱ꞉ᴟꜛᴒᴑͼԜᴡᴡԜᴐꞋᴠͼԝᴒⱱꜝᴟᴒͼᴡⱳᴒͼ᷾ͼᴤᴒᴒꞋᴠͼⱳԜᴣᴒͼᴒꜜᴑᴒᴑ᷅ͼᴁⱳᴒͼᴟᴢꜜ᷄꞉ꜜͼ
ꜞᴒᴟ꞉ꜝᴑͼꜛԜᴦͼԝᴒͼᴒᴥꜞԜꜜᴑᴒᴑͼԝᴦͼԜꜜͼԜᴑᴑ꞉ᴡ꞉ꜝꜜԜꞌͼ᷾ͼᴤᴒᴒꞋᴠͼ꞉ⱱͼᴡⱳᴒͼᴠᴢԝ꞊ᴒᴐᴡͼᴑꜝᴒᴠͼꜜꜝᴡͼꜛᴒᴒᴡͼᴡⱳᴒͼꜛ꞉ꜜ꞉ꜛᴢꜛͼ
ԜᴡᴡԜᴐꞋͼᴟᴒꜟᴢ꞉ᴟᴒꜛᴒꜜᴡͼᴑᴢᴟ꞉ꜜⱲͼᴡⱳᴒͼⱱ꞉ᴟᴠᴡͼ᷾ͼᴤᴒᴒꞋᴠ᷅
ᴁⱳᴒͼⱱꜝꞌꞌꜝᴤ꞉ꜜⱲͼᴤ꞉ꞌꞌͼԝᴒͼᴐꜝꞌꞌᴒᴐᴡᴒᴑͼꜝꜜͼԜꜜͼꜝꜜⱲꜝ꞉ꜜⱲͼԝԜᴠ꞉ᴠͼᴑᴢᴟ꞉ꜜⱲͼᴡⱳᴒͼᴟᴢꜜ᷄꞉ꜜͼꜞᴒᴟ꞉ꜝᴑͼԝᴦͼᴠᴢԝ꞊ᴒᴐᴡᴠͼӿꜝᴟͼ
ᴐԜᴟᴒⱲ꞉ᴣᴒᴟᴠԐͼᴟᴒꜞꜝᴟᴡ꞉ꜜⱲͼᴠᴦꜛꜞᴡꜝꜛᴠͼꜝⱱͼԜꜜͼⱶⱨⱬͼԜᴡᴡԜᴐꞋͼᴡꜝͼᴡⱳᴒͼᴠ꞉ᴡᴒͼꜝᴟͼᴡⱳᴟꜝᴢⱲⱳͼᴟᴒⱲᴢꞌԜᴟͼᴠ꞉ᴡᴒͼᴐꜝꜜᴡԜᴐᴡͼᴤ꞉ᴡⱳͼ
ᴡⱳᴒͼᴠᴢԝ꞊ᴒᴐᴡͼӿꜝᴟͼᴐԜᴟᴒⱲ꞉ᴣᴒᴟԐⱡ

Ⱬᴅ᷄᷉Ⱡ᷊᷇
ⱪꞌ꞉ꜜ꞉ᴐԜꞌͼᴁᴟ꞉Ԝꞌͼ͟ᴟꜝᴡꜝᴐꜝꞌⱡͼⱫᴅ᷄᷉Ⱡ᷊᷊᷇᷄᷇
ⱨꜛᴒꜜᴑꜛᴒꜜᴡͼ᷊᷅᷇ͼⱴ꞉ꜜԜꞌⱡͼ᷇ⱠͼꜗԜꜜᴢԜᴟᴦ᷉᷇᷈ⅎ
ⱪꜝꜜⱱ꞉ᴑᴒꜜᴡ꞉Ԝꞌ
͟ԜⱲᴒͼ⅍ⅎ
ⱫᴦԜᴥͼⱪꜝᴟꜞ᷅
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͟ᴟ꞉ꜝᴟͼԜꜜᴑͼᴐꜝꜜᴐꜝꜛ꞉ᴡԜꜜᴡͼᴡⱳᴒᴟԜꜞᴦͼӿᴀᴒᴐᴡ꞉ꜝꜜͼ⅍᷅᷈᷉Ԑ
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ⱶⱨⱬͼԜᴡᴡԜᴐꞋͼ꞉ꜜⱱꜝᴟꜛԜᴡ꞉ꜝꜜͼӿᴀᴒᴐᴡ꞉ꜝꜜͼ⅍᷅᷾Ԑ
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ⱨⱬͼᴐꜝꞌꞌᴒᴐᴡ꞉ꜝꜜͼӿᴀᴒᴐᴡ꞉ꜝꜜͼ⅍᷅᷈⅍Ԑ
7.3
Start of Treatment Period: Visit 1, Dose 1 (Day 0)
ᴁⱳᴒͼⱱꜝꞌꞌꜝᴤ꞉ꜜⱲͼꜞᴟꜝᴐᴒᴑᴢᴟᴒᴠͼԜꜜᴑͼԜᴠᴠᴒᴠᴠꜛᴒꜜᴡᴠͼԜᴟᴒͼᴡꜝͼԝᴒͼꜞᴒᴟⱱꜝᴟꜛᴒᴑͼꜝꜜͼⱫԜᴦ᷇ͼꜞᴟ꞉ꜝᴟᴡꜝͼᴡⱳᴒͼⱱ꞉ᴟᴠᴡͼᴑꜝᴠᴒͼꜝⱱͼ
ⱷꜚ͟ͼԜᴑꜛ꞉ꜜ꞉ᴠᴡᴟԜᴡ꞉ꜝꜜⱡ
ᶄ
ⱬꞌ꞉Ⱳ꞉ԝ꞉ꞌ꞉ᴡᴦͼᴟᴒᴣ꞉ᴒᴤͼӿᴀᴒᴐᴡ꞉ꜝꜜͼ⅍᷅᷉Ԑ
ᶄ
ϸԜꜜᴑꜝꜛ꞉ᴧԜᴡ꞉ꜝꜜͼᴡꜝͼᴡᴟᴒԜᴡꜛᴒꜜᴡͼӿᴀᴒᴐᴡ꞉ꜝꜜͼ⅍᷊᷅᷈Ԑ
ᶄ
ᴂᴟ꞉ꜜᴒͼꜞᴟᴒⱲꜜԜꜜᴐᴦͼᴡᴒᴠᴡͼӿⱱᴒꜛԜꞌᴒᴠԐͼӿᴀᴒᴐᴡ꞉ꜝꜜͼ⅍᷅˲Ԑ
ᶄ
ᴃ꞉ᴡԜꞌͼᴠ꞉Ⱳꜜᴠͼ꞉ꜜᴐꞌᴢᴑ꞉ꜜⱲͼԝꜝᴑᴦͼᴡᴒꜛꜞᴒᴟԜᴡᴢᴟᴒԓͼⱶϸԓͼⱩ͟ͼԜꜜᴑͼϸϸͼӿᴀᴒᴐᴡ꞉ꜝꜜ⅍᷿᷅Ԑ
ᶄ
ⱪꜝꜛꜞꞌᴒᴡᴒͼꜞⱳᴦᴠ꞉ᴐԜꞌͼᴒᴥԜꜛ꞉ꜜԜᴡ꞉ꜝꜜͼӿᴀᴒᴐᴡ꞉ꜝꜜͼ⅍᷅⅍Ԑ
ᶄ
᷈᷉᷄ꜙᴒԜᴑͼⱬⱪⱵͼӿᴀᴒᴐᴡ꞉ꜝꜜͼ⅍᷅ⅎԐ
ᶄ
ꜙԜԝꜝᴟԜᴡꜝᴟᴦͼᴡᴒᴠᴡ꞉ꜜⱲͼ꞉ꜜᴐꞌᴢᴑ꞉ꜜⱲͼⱳᴒꜛԜᴡꜝꞌꜝⱲᴦԓͼᴐꜝԜⱲᴢꞌԜᴡ꞉ꜝꜜԓͼᴠᴒᴟᴢꜛͼᴐⱳᴒꜛ꞉ᴠᴡᴟᴦͼԜꜜᴑͼᴢᴟ꞉ꜜԜꞌᴦᴠ꞉ᴠͼ
ӿᴀᴒᴐᴡ꞉ꜝꜜͼ⅍᷅˲Ԑ
ᶄ
͟ꜘͼԝԜᴠᴒꞌ꞉ꜜᴒͼᴠԜꜛꜞꞌᴒͼᴐꜝꞌꞌᴒᴐᴡ꞉ꜝꜜͼӿᴀᴒᴐᴡ꞉ꜝꜜͼ⅍᷅ⱠԐ
ᶄ
͟ⱫͼԝԜᴠᴒꞌ꞉ꜜᴒͼᴠԜꜛꜞꞌᴒͼᴐꜝꞌꞌᴒᴐᴡ꞉ꜝꜜͼӿᴀᴒᴐᴡ꞉ꜝꜜͼ⅍᷅᷈᷇Ԑ
ᶄ
ⱩԜᴠᴒꞌ꞉ꜜᴒͼԜꜜᴡ꞉᷄ᴑᴟᴢⱲͼԜꜜᴡ꞉ԝꜝᴑᴦͼᴠԜꜛꜞꞌᴒͼᴐꜝꞌꞌᴒᴐᴡ꞉ꜝꜜͼӿᴀᴒᴐᴡ꞉ꜝꜜͼ⅍᷅᷈᷈Ԑ
ᶄ
͟ᴟ꞉ꜝᴟͼԜꜜᴑͼᴐꜝꜜᴐꜝꜛ꞉ᴡԜꜜᴡͼᴡⱳᴒᴟԜꜞᴦͼӿᴀᴒᴐᴡ꞉ꜝꜜͼ⅍᷅᷈᷉Ԑ
ᶄ
ⱶⱨⱬͼԜᴡᴡԜᴐꞋͼ꞉ꜜⱱꜝᴟꜛԜᴡ꞉ꜝꜜͼӿᴀᴒᴐᴡ꞉ꜝꜜͼ⅍᷅᷾Ԑ
ᶄ
ⱨⱬͼᴐꜝꞌꞌᴒᴐᴡ꞉ꜝꜜͼӿᴀᴒᴐᴡ꞉ꜝꜜͼ⅍᷅᷈⅍Ԑ
ᶄ
ϷᴢԜꞌ꞉ᴡᴦͼꜝⱱͼꞌ꞉ⱱᴒͼԜᴠᴠᴒᴠᴠꜛᴒꜜᴡᴠⱡͼⱬϷ᷿ⱫͼԜꜜᴑͼⱨⱬ᷄Ϸꜝꜙͼӿᴀᴒᴐᴡ꞉ꜝꜜͼ⅍᷿᷅᷈Ԑ
ⱨⱱᴡᴒᴟͼᴡⱳᴒͼꜞᴟᴒᴐᴒᴑ꞉ꜜⱲͼꜞᴟꜝᴐᴒᴑᴢᴟᴒᴠͼԜꜜᴑͼԜᴠᴠᴒᴠᴠꜛᴒꜜᴡᴠͼԜᴟᴒͼᴐꜝꜛꜞꞌᴒᴡᴒᴑⱡ
ᶄ
ⱨᴑꜛ꞉ꜜ꞉ᴠᴡᴒᴟͼⱷꜚ͟ͼӿᴀᴒᴐᴡ꞉ꜝꜜͼ⅍᷅᷈᷾Ԑ
ⱨⱱᴡᴒᴟͼԜᴑꜛ꞉ꜜ꞉ᴠᴡᴟԜᴡ꞉ꜝꜜͼꜝⱱͼⱷꜚ͟ԓͼᴡⱳᴒͼⱱꜝꞌꞌꜝᴤ꞉ꜜⱲͼꜞꜝᴠᴡͼᴡᴟᴒԜᴡꜛᴒꜜᴡͼꜞᴟꜝᴐᴒᴑᴢᴟᴒᴠͼԜꜜᴑͼԜᴠᴠᴒᴠᴠꜛᴒꜜᴡᴠͼᴤ꞉ꞌꞌͼԝᴒͼ
ꜞᴒᴟⱱꜝᴟꜛᴒᴑⱡ

Ⱬᴅ᷄᷉Ⱡ᷊᷇
ⱪꞌ꞉ꜜ꞉ᴐԜꞌͼᴁᴟ꞉Ԝꞌͼ͟ᴟꜝᴡꜝᴐꜝꞌⱡͼⱫᴅ᷄᷉Ⱡ᷊᷊᷇᷄᷇
ⱨꜛᴒꜜᴑꜛᴒꜜᴡͼ᷊᷅᷇ͼⱴ꞉ꜜԜꞌⱡͼ᷇ⱠͼꜗԜꜜᴢԜᴟᴦ᷉᷇᷈ⅎ
ⱪꜝꜜⱱ꞉ᴑᴒꜜᴡ꞉Ԝꞌ
͟ԜⱲᴒͼ⅍˲
ⱫᴦԜᴥͼⱪꜝᴟꜞ᷅
ᶄ
ᴃ꞉ᴡԜꞌͼᴠ꞉Ⱳꜜᴠͼ꞉ꜜᴐꞌᴢᴑ꞉ꜜⱲͼԝꜝᴑᴦͼᴡᴒꜛꜞᴒᴟԜᴡᴢᴟᴒԓͼⱶϸԓͼⱩ͟ͼԜꜜᴑͼϸϸͼӿᴀᴒᴐᴡ꞉ꜝꜜͼ⅍᷿᷅ԐͼԜᴡͼ᷈ͼԜꜜᴑͼ᷉ⱳꜝᴢᴟᴠͼꜞꜝᴠᴡ᷄
ᴑꜝᴠᴒ
ᶄ
ⱪꜝꜜᴐꜝꜛ꞉ᴡԜꜜᴡͼᴡⱳᴒᴟԜꜞᴦͼӿᴀᴒᴐᴡ꞉ꜝꜜͼ⅍᷅᷈᷉Ԑ
ᶄ
ⱨⱬͼᴐꜝꞌꞌᴒᴐᴡ꞉ꜝꜜͼӿᴀᴒᴐᴡ꞉ꜝꜜͼ⅍᷅᷈⅍Ԑ
7.4
Site Contact with the Subject
ᴀ꞉ᴡᴒͼꜞᴒᴟᴠꜝꜜꜜᴒꞌͼᴐꜝꜜᴡԜᴐᴡͼᴡⱳᴒͼᴠᴢԝ꞊ᴒᴐᴡͼꜝꜜᴐᴒͼԝᴒᴡᴤᴒᴒꜜͼᴠᴐⱳᴒᴑᴢꞌᴒᴑͼᴠᴡᴢᴑᴦͼᴣ꞉ᴠ꞉ᴡᴠͼꜝᴟͼԜꜞꜞᴟꜝᴥ꞉ꜛԜᴡᴒꞌᴦͼⅎͼᴑԜᴦᴠͼ
Ԝⱱᴡᴒᴟͼᴡⱳᴒ꞉ᴟͼꞌԜᴠᴡͼᴐꜝꜜᴡԜᴐᴡͼᴤ꞉ᴡⱳͼᴡⱳᴒͼᴠᴢԝ꞊ᴒᴐᴡͼᴡꜝͼᴠꜝꞌ꞉ᴐ꞉ᴡͼⱱꜝᴟͼԜꜜᴦͼⱶⱨⱬͼԜᴡᴡԜᴐꞋͼ꞉ꜜⱱꜝᴟꜛԜᴡ꞉ꜝꜜͼꜜꜝᴡͼԜꞌᴟᴒԜᴑᴦͼ
ᴟᴒꜞꜝᴟᴡᴒᴑͼԝᴦͼᴡⱳᴒͼᴠᴢԝ꞊ᴒᴐᴡ᷅
ᶄ
ⱪꜝꜜᴐꜝꜛ꞉ᴡԜꜜᴡͼᴡⱳᴒᴟԜꜞᴦͼӿᴀᴒᴐᴡ꞉ꜝꜜͼ⅍᷅᷈᷉Ԑ
ᶄ
ⱶⱨⱬͼԜᴡᴡԜᴐꞋͼ꞉ꜜⱱꜝᴟꜛԜᴡ꞉ꜝꜜͼӿᴀᴒᴐᴡ꞉ꜝꜜͼ⅍᷅᷾Ԑ
ᶄ
ⱨⱬͼᴐꜝꞌꞌᴒᴐᴡ꞉ꜝꜜͼӿᴀᴒᴐᴡ꞉ꜝꜜͼ⅍᷅᷈⅍Ԑ
7.5
Continuation of Treatment Period: Visit 2, Dose 2 (Day 14±3 Days)
꜡ꜜͼⱫԜᴦͼ᷈᷾ͼᴡⱳᴒͼⱱꜝꞌꞌꜝᴤ꞉ꜜⱲͼꜞᴟꜝᴐᴒᴑᴢᴟᴒᴠͼԜꜜᴑͼԜᴠᴠᴒᴠᴠꜛᴒꜜᴡᴠͼᴤ꞉ꞌꞌͼԝᴒͼꜞᴒᴟⱱꜝᴟꜛᴒᴑͼꜞᴟ꞉ꜝᴟͼᴡꜝͼⱷꜚ͟ͼ
Ԝᴑꜛ꞉ꜜ꞉ᴠᴡᴟԜᴡ꞉ꜝꜜⱡ
ᶄ
ᴃ꞉ᴡԜꞌͼᴠ꞉Ⱳꜜᴠͼ꞉ꜜᴐꞌᴢᴑ꞉ꜜⱲͼԝꜝᴑᴦͼᴡᴒꜛꜞᴒᴟԜᴡᴢᴟᴒԓͼⱶϸԓͼⱩ͟ͼԜꜜᴑͼϸϸͼӿᴀᴒᴐᴡ꞉ꜝꜜ⅍᷿᷅Ԑ
ᶄ
ⱪꜝꜜᴐꜝꜛ꞉ᴡԜꜜᴡͼᴡⱳᴒᴟԜꜞᴦͼӿᴀᴒᴐᴡ꞉ꜝꜜͼ⅍᷅᷈᷉Ԑ
ᶄ
ⱶⱨⱬͼԜᴡᴡԜᴐꞋͼ꞉ꜜⱱꜝᴟꜛԜᴡ꞉ꜝꜜͼӿᴀᴒᴐᴡ꞉ꜝꜜͼ⅍᷅᷾Ԑ
ᶄ
ⱨⱬͼᴐꜝꞌꞌᴒᴐᴡ꞉ꜝꜜͼӿᴀᴒᴐᴡ꞉ꜝꜜͼ⅍᷅᷈⅍Ԑ
ⱨⱱᴡᴒᴟͼᴡⱳᴒͼꜞᴟᴒᴐᴒᴑ꞉ꜜⱲͼꜞᴟꜝᴐᴒᴑᴢᴟᴒᴠͼԜꜜᴑͼԜᴠᴠᴒᴠᴠꜛᴒꜜᴡᴠͼԜᴟᴒͼᴐꜝꜛꜞꞌᴒᴡᴒᴑⱡ
ᶄ
ⱨᴑꜛ꞉ꜜ꞉ᴠᴡᴒᴟͼⱷꜚ͟ͼӿᴀᴒᴐᴡ꞉ꜝꜜͼ⅍᷅᷈᷾Ԑ
ⱨⱱᴡᴒᴟͼԜᴑꜛ꞉ꜜ꞉ᴠᴡᴟԜᴡ꞉ꜝꜜͼꜝⱱͼⱷꜚ͟ԓͼᴡⱳᴒͼⱱꜝꞌꞌꜝᴤ꞉ꜜⱲͼꜞꜝᴠᴡͼᴡᴟᴒԜᴡꜛᴒꜜᴡͼꜞᴟꜝᴐᴒᴑᴢᴟᴒᴠͼԜꜜᴑͼԜᴠᴠᴒᴠᴠꜛᴒꜜᴡᴠᴤ꞉ꞌꞌͼԝᴒͼ
ꜞᴒᴟⱱꜝᴟꜛᴒᴑⱡ
ᶄ
ᴃ꞉ᴡԜꞌͼᴠ꞉Ⱳꜜᴠͼ꞉ꜜᴐꞌᴢᴑ꞉ꜜⱲͼԝꜝᴑᴦͼᴡᴒꜛꜞᴒᴟԜᴡᴢᴟᴒԓͼⱶϸԓͼⱩ͟ͼԜꜜᴑͼϸϸͼӿᴀᴒᴐᴡ꞉ꜝꜜ⅍᷿᷅ԐͼԜᴡͼ᷈ͼԜꜜᴑͼ᷉ⱳꜝᴢᴟᴠͼꜞꜝᴠᴡ᷄
ᴑꜝᴠᴒ
ᶄ
ⱪꜝꜜᴐꜝꜛ꞉ᴡԜꜜᴡͼᴡⱳᴒᴟԜꜞᴦͼӿᴀᴒᴐᴡ꞉ꜝꜜͼ⅍᷅᷈᷉Ԑ
ᶄ
ⱨⱬͼᴐꜝꞌꞌᴒᴐᴡ꞉ꜝꜜͼӿᴀᴒᴐᴡ꞉ꜝꜜͼ⅍᷅᷈⅍Ԑ

Ⱬᴅ᷄᷉Ⱡ᷊᷇
ⱪꞌ꞉ꜜ꞉ᴐԜꞌͼᴁᴟ꞉Ԝꞌͼ͟ᴟꜝᴡꜝᴐꜝꞌⱡͼⱫᴅ᷄᷉Ⱡ᷊᷊᷇᷄᷇
ⱨꜛᴒꜜᴑꜛᴒꜜᴡͼ᷊᷅᷇ͼⱴ꞉ꜜԜꞌⱡͼ᷇ⱠͼꜗԜꜜᴢԜᴟᴦ᷉᷇᷈ⅎ
ⱪꜝꜜⱱ꞉ᴑᴒꜜᴡ꞉Ԝꞌ
͟ԜⱲᴒͼ⅍Ⱡ
ⱫᴦԜᴥͼⱪꜝᴟꜞ᷅
7.6
Continuation of Treatment Period: Visit 3, Dose 3 (Day 28±3 Days)
꜡ꜜͼⱫԜᴦͼ᷉˲ԓ ᴡⱳᴒͼⱱꜝꞌꞌꜝᴤ꞉ꜜⱲͼꜞᴟꜝᴐᴒᴑᴢᴟᴒᴠͼԜꜜᴑͼԜᴠᴠᴒᴠᴠꜛᴒꜜᴡᴠͼᴤ꞉ꞌꞌͼԝᴒͼꜞᴒᴟⱱꜝᴟꜛᴒᴑͼꜞᴟ꞉ꜝᴟͼᴡꜝͼⱷꜚ͟ͼ
Ԝᴑꜛ꞉ꜜ꞉ᴠᴡᴟԜᴡ꞉ꜝꜜⱡ
ᶄ
ᴃ꞉ᴡԜꞌͼᴠ꞉Ⱳꜜᴠͼ꞉ꜜᴐꞌᴢᴑ꞉ꜜⱲͼԝꜝᴑᴦͼᴡᴒꜛꜞᴒᴟԜᴡᴢᴟᴒԓͼⱶϸԓͼⱩ͟ͼԜꜜᴑͼϸϸͼӿᴀᴒᴐᴡ꞉ꜝꜜ⅍᷿᷅Ԑ
ᶄ
ⱪꜝꜛꜞꞌᴒᴡᴒͼꜞⱳᴦᴠ꞉ᴐԜꞌͼᴒᴥԜꜛ꞉ꜜԜᴡ꞉ꜝꜜͼӿᴀᴒᴐᴡ꞉ꜝꜜͼ⅍᷅⅍Ԑ
ᶄ
ꜙԜԝꜝᴟԜᴡꜝᴟᴦͼᴡᴒᴠᴡ꞉ꜜⱲͼ꞉ꜜᴐꞌᴢᴑ꞉ꜜⱲͼⱳᴒꜛԜᴡꜝꞌꜝⱲᴦԓͼᴐꜝԜⱲᴢꞌԜᴡ꞉ꜝꜜԓͼᴠᴒᴟᴢꜛͼᴐⱳᴒꜛ꞉ᴠᴡᴟᴦͼԜꜜᴑͼᴢᴟ꞉ꜜԜꞌᴦᴠ꞉ᴠͼ
ӿᴀᴒᴐᴡ꞉ꜝꜜͼ⅍᷅˲Ԑ
ᶄ
͟ᴟᴒⱲꜜԜꜜᴐᴦͼᴡᴒᴠᴡԓͼᴠᴒᴟᴢꜛͼꜝᴟͼᴢᴟ꞉ꜜᴒͼӿⱱᴒꜛԜꞌᴒᴠԐͼӿᴀᴒᴐᴡ꞉ꜝꜜͼ⅍᷅˲Ԑ
ᶄ
ⱪꜝꜜᴐꜝꜛ꞉ᴡԜꜜᴡͼᴡⱳᴒᴟԜꜞᴦͼӿᴀᴒᴐᴡ꞉ꜝꜜͼ⅍᷅᷈᷉Ԑ
ᶄ
ⱶⱨⱬͼԜᴡᴡԜᴐꞋͼ꞉ꜜⱱꜝᴟꜛԜᴡ꞉ꜝꜜͼӿᴀᴒᴐᴡ꞉ꜝꜜͼ⅍᷅᷾Ԑ
ᶄ
ⱨⱬͼᴐꜝꞌꞌᴒᴐᴡ꞉ꜝꜜͼӿᴀᴒᴐᴡ꞉ꜝꜜͼ⅍᷅᷈⅍Ԑ
ᶄ
ϷᴢԜꞌ꞉ᴡᴦͼꜝⱱͼꞌ꞉ⱱᴒͼԜᴠᴠᴒᴠᴠꜛᴒꜜᴡᴠⱡͼⱨⱬ᷄Ϸꜝꜙͼӿᴀᴒᴐᴡ꞉ꜝꜜͼ⅍᷿᷅᷈Ԑ
ⱨⱱᴡᴒᴟͼᴡⱳᴒͼꜞᴟᴒᴐᴒᴑ꞉ꜜⱲͼꜞᴟꜝᴐᴒᴑᴢᴟᴒᴠͼԜꜜᴑͼԜᴠᴠᴒᴠᴠꜛᴒꜜᴡᴠͼԜᴟᴒͼᴐꜝꜛꜞꞌᴒᴡᴒᴑⱡ
ᶄ
ⱨᴑꜛ꞉ꜜ꞉ᴠᴡᴒᴟͼⱷꜚ͟ͼӿᴀᴒᴐᴡ꞉ꜝꜜͼ⅍᷅᷈᷾Ԑ
ⱨⱱᴡᴒᴟͼԜᴑꜛ꞉ꜜ꞉ᴠᴡᴟԜᴡ꞉ꜝꜜͼꜝⱱͼⱷꜚ͟ԓͼᴡⱳᴒͼⱱꜝꞌꞌꜝᴤ꞉ꜜⱲͼꜞꜝᴠᴡͼᴡᴟᴒԜᴡꜛᴒꜜᴡͼꜞᴟꜝᴐᴒᴑᴢᴟᴒᴠͼԜꜜᴑͼԜᴠᴠᴒᴠᴠꜛᴒꜜᴡᴠͼᴤ꞉ꞌꞌͼԝᴒͼ
ꜞᴒᴟⱱꜝᴟꜛᴒᴑⱡ
ᶄ
ᴃ꞉ᴡԜꞌͼᴠ꞉Ⱳꜜᴠͼ꞉ꜜᴐꞌᴢᴑ꞉ꜜⱲͼԝꜝᴑᴦͼᴡᴒꜛꜞᴒᴟԜᴡᴢᴟᴒԓͼⱶϸԓͼⱩ͟ͼԜꜜᴑͼϸϸͼӿᴀᴒᴐᴡ꞉ꜝꜜ⅍᷿᷅ԐͼԜᴡͼ᷈ͼԜꜜᴑͼ᷉ⱳꜝᴢᴟᴠͼꜞꜝᴠᴡ᷄
ᴑꜝᴠᴒ
ᶄ
ⱪꜝꜜᴐꜝꜛ꞉ᴡԜꜜᴡͼᴡⱳᴒᴟԜꜞᴦͼӿᴀᴒᴐᴡ꞉ꜝꜜͼ⅍᷅᷈᷉Ԑ
ᶄ
ⱨⱬͼᴐꜝꞌꞌᴒᴐᴡ꞉ꜝꜜͼӿᴀᴒᴐᴡ꞉ꜝꜜͼ⅍᷅᷈⅍Ԑ
7.7
Continuation of Treatment Period: Visit 4, Dose 4 (Day 42 ±3 Days)
꜡ꜜͼⱫԜᴦͼ᷾᷉ԓͼᴡⱳᴒͼⱱꜝꞌꞌꜝᴤ꞉ꜜⱲͼꜞᴟꜝᴐᴒᴑᴢᴟᴒᴠͼԜꜜᴑͼԜᴠᴠᴒᴠᴠꜛᴒꜜᴡᴠͼᴤ꞉ꞌꞌͼԝᴒͼꜞᴒᴟⱱꜝᴟꜛᴒᴑͼꜞᴟ꞉ꜝᴟͼᴡꜝͼⱷꜚ͟ͼ
Ԝᴑꜛ꞉ꜜ꞉ᴠᴡᴟԜᴡ꞉ꜝꜜⱡ
ᶄ
ᴃ꞉ᴡԜꞌͼᴠ꞉Ⱳꜜᴠͼ꞉ꜜᴐꞌᴢᴑ꞉ꜜⱲͼԝꜝᴑᴦͼᴡᴒꜛꜞᴒᴟԜᴡᴢᴟᴒԓͼⱶϸԓͼⱩ͟ͼԜꜜᴑͼϸϸͼӿᴀᴒᴐᴡ꞉ꜝꜜ⅍᷿᷅Ԑ
ᶄ
ⱪꜝꜜᴐꜝꜛ꞉ᴡԜꜜᴡͼᴡⱳᴒᴟԜꜞᴦͼӿᴀᴒᴐᴡ꞉ꜝꜜͼ⅍᷅᷈᷉Ԑ
ᶄ
ⱶⱨⱬͼԜᴡᴡԜᴐꞋͼ꞉ꜜⱱꜝᴟꜛԜᴡ꞉ꜝꜜͼӿᴀᴒᴐᴡ꞉ꜝꜜͼ⅍᷅᷾Ԑ

Ⱬᴅ᷄᷉Ⱡ᷊᷇
ⱪꞌ꞉ꜜ꞉ᴐԜꞌͼᴁᴟ꞉Ԝꞌͼ͟ᴟꜝᴡꜝᴐꜝꞌⱡͼⱫᴅ᷄᷉Ⱡ᷊᷊᷇᷄᷇
ⱨꜛᴒꜜᴑꜛᴒꜜᴡͼ᷊᷅᷇ͼⱴ꞉ꜜԜꞌⱡͼ᷇ⱠͼꜗԜꜜᴢԜᴟᴦ᷉᷇᷈ⅎ
ⱪꜝꜜⱱ꞉ᴑᴒꜜᴡ꞉Ԝꞌ
͟ԜⱲᴒͼⅎ᷇
ⱫᴦԜᴥͼⱪꜝᴟꜞ᷅
ᶄ
ⱨⱬͼᴐꜝꞌꞌᴒᴐᴡ꞉ꜝꜜͼӿᴀᴒᴐᴡ꞉ꜝꜜͼ⅍᷅᷈⅍Ԑ
ⱨⱱᴡᴒᴟͼᴡⱳᴒͼꜞᴟᴒᴐᴒᴑ꞉ꜜⱲͼꜞᴟꜝᴐᴒᴑᴢᴟᴒᴠͼԜꜜᴑͼԜᴠᴠᴒᴠᴠꜛᴒꜜᴡᴠͼԜᴟᴒͼᴐꜝꜛꜞꞌᴒᴡᴒᴑⱡ
ᶄ
ⱨᴑꜛ꞉ꜜ꞉ᴠᴡᴒᴟͼⱷꜚ͟ͼӿᴀᴒᴐᴡ꞉ꜝꜜͼ⅍᷅᷈᷾Ԑ
ⱨⱱᴡᴒᴟͼԜᴑꜛ꞉ꜜ꞉ᴠᴡᴟԜᴡ꞉ꜝꜜͼꜝⱱͼⱷꜚ͟ԓͼᴡⱳᴒͼⱱꜝꞌꞌꜝᴤ꞉ꜜⱲͼꜞꜝᴠᴡͼᴡᴟᴒԜᴡꜛᴒꜜᴡͼꜞᴟꜝᴐᴒᴑᴢᴟᴒᴠͼԜꜜᴑͼԜᴠᴠᴒᴠᴠꜛᴒꜜᴡᴠͼᴤ꞉ꞌꞌͼԝᴒͼ
ꜞᴒᴟⱱꜝᴟꜛᴒᴑⱡ
ᶄ
ᴃ꞉ᴡԜꞌͼᴠ꞉Ⱳꜜᴠͼ꞉ꜜᴐꞌᴢᴑ꞉ꜜⱲͼԝꜝᴑᴦͼᴡᴒꜛꜞᴒᴟԜᴡᴢᴟᴒԓͼⱶϸԓͼⱩ͟ͼԜꜜᴑͼϸϸͼӿᴀᴒᴐᴡ꞉ꜝꜜ⅍᷿᷅ԐͼԜᴡͼ᷈ͼԜꜜᴑͼ᷉ⱳꜝᴢᴟᴠͼꜞꜝᴠᴡ᷄
ᴑꜝᴠᴒ
ᶄ
ⱪꜝꜜᴐꜝꜛ꞉ᴡԜꜜᴡͼᴡⱳᴒᴟԜꜞᴦͼӿᴀᴒᴐᴡ꞉ꜝꜜͼ⅍᷅᷈᷉Ԑ
ᶄ
ⱨⱬͼᴐꜝꞌꞌᴒᴐᴡ꞉ꜝꜜͼӿᴀᴒᴐᴡ꞉ꜝꜜͼ⅍᷅᷈⅍Ԑ
7.8
Continuation of Treatment Period: Visit 5, Dose 5 (Day 56±3 Days)
꜡ꜜͼⱫԜᴦͼ᷿⅍ԓͼᴡⱳᴒͼⱱꜝꞌꞌꜝᴤ꞉ꜜⱲͼꜞᴟꜝᴐᴒᴑᴢᴟᴒᴠͼԜꜜᴑͼԜᴠᴠᴒᴠᴠꜛᴒꜜᴡᴠͼᴤ꞉ꞌꞌͼԝᴒͼꜞᴒᴟⱱꜝᴟꜛᴒᴑͼꜞᴟ꞉ꜝᴟͼᴡꜝͼⱷꜚ͟ͼ
Ԝᴑꜛ꞉ꜜ꞉ᴠᴡᴟԜᴡ꞉ꜝꜜⱡ
ᶄ
ᴃ꞉ᴡԜꞌͼᴠ꞉Ⱳꜜᴠͼ꞉ꜜᴐꞌᴢᴑ꞉ꜜⱲͼԝꜝᴑᴦͼᴡᴒꜛꜞᴒᴟԜᴡᴢᴟᴒԓͼⱶϸԓͼⱩ͟ͼԜꜜᴑͼϸϸͼӿᴀᴒᴐᴡ꞉ꜝꜜ⅍᷿᷅Ԑ
ᶄ
ⱪꜝꜛꜞꞌᴒᴡᴒͼꜞⱳᴦᴠ꞉ᴐԜꞌͼᴒᴥԜꜛ꞉ꜜԜᴡ꞉ꜝꜜͼӿᴀᴒᴐᴡ꞉ꜝꜜͼ⅍᷅⅍Ԑ
ᶄ
᷈᷉᷄ꜙᴒԜᴑͼⱬⱪⱵͼӿᴀᴒᴐᴡ꞉ꜝꜜͼ⅍᷅ⅎԐ
ᶄ
ꜙԜԝꜝᴟԜᴡꜝᴟᴦͼᴡᴒᴠᴡ꞉ꜜⱲͼ꞉ꜜᴐꞌᴢᴑ꞉ꜜⱲͼⱳᴒꜛԜᴡꜝꞌꜝⱲᴦԓͼᴐꜝԜⱲᴢꞌԜᴡ꞉ꜝꜜԓͼᴠᴒᴟᴢꜛͼᴐⱳᴒꜛ꞉ᴠᴡᴟᴦͼԜꜜᴑͼᴢᴟ꞉ꜜԜꞌᴦᴠ꞉ᴠͼ
ӿᴀᴒᴐᴡ꞉ꜝꜜͼ⅍᷅˲Ԑ
ᶄ
͟ᴟᴒⱲꜜԜꜜᴐᴦͼᴡᴒᴠᴡԓͼᴠᴒᴟᴢꜛͼꜝᴟͼᴢᴟ꞉ꜜᴒͼӿⱱᴒꜛԜꞌᴒᴠԐͼӿᴀᴒᴐᴡ꞉ꜝꜜͼ⅍᷅˲Ԑ
ᶄ
͟ꜘͼᴠԜꜛꜞꞌᴒͼᴐꜝꞌꞌᴒᴐᴡ꞉ꜝꜜͼӿᴀᴒᴐᴡ꞉ꜝꜜͼ⅍᷅ⱠԐ
ᶄ
͟ⱫͼᴠԜꜛꜞꞌᴒͼᴐꜝꞌꞌᴒᴐᴡ꞉ꜝꜜͼӿᴀᴒᴐᴡ꞉ꜝꜜͼ⅍᷅᷈᷇Ԑ
ᶄ
ⱨꜜᴡ꞉᷄ᴑᴟᴢⱲͼԜꜜᴡ꞉ԝꜝᴑᴦͼᴠԜꜛꜞꞌᴒͼᴐꜝꞌꞌᴒᴐᴡ꞉ꜝꜜͼӿᴀᴒᴐᴡ꞉ꜝꜜͼ⅍᷅᷈᷈Ԑ
ᶄ
ⱪꜝꜜᴐꜝꜛ꞉ᴡԜꜜᴡͼᴡⱳᴒᴟԜꜞᴦͼӿᴀᴒᴐᴡ꞉ꜝꜜͼ⅍᷅᷈᷉Ԑ
ᶄ
ⱶⱨⱬͼԜᴡᴡԜᴐꞋͼ꞉ꜜⱱꜝᴟꜛԜᴡ꞉ꜝꜜͼӿᴀᴒᴐᴡ꞉ꜝꜜͼ⅍᷅᷾Ԑ
ᶄ
ⱨⱬͼᴐꜝꞌꞌᴒᴐᴡ꞉ꜝꜜͼӿᴀᴒᴐᴡ꞉ꜝꜜͼ⅍᷅᷈⅍Ԑ
ᶄ
ϷᴢԜꞌ꞉ᴡᴦͼꜝⱱͼꞌ꞉ⱱᴒͼԜᴠᴠᴒᴠᴠꜛᴒꜜᴡᴠⱡͼⱨⱬ᷄Ϸꜝꜙͼӿᴀᴒᴐᴡ꞉ꜝꜜ⅍᷿᷅᷈Ԑ

Ⱬᴅ᷄᷉Ⱡ᷊᷇
ⱪꞌ꞉ꜜ꞉ᴐԜꞌͼᴁᴟ꞉Ԝꞌͼ͟ᴟꜝᴡꜝᴐꜝꞌⱡͼⱫᴅ᷄᷉Ⱡ᷊᷊᷇᷄᷇
ⱨꜛᴒꜜᴑꜛᴒꜜᴡͼ᷊᷅᷇ͼⱴ꞉ꜜԜꞌⱡͼ᷇ⱠͼꜗԜꜜᴢԜᴟᴦ᷉᷇᷈ⅎ
ⱪꜝꜜⱱ꞉ᴑᴒꜜᴡ꞉Ԝꞌ
͟ԜⱲᴒͼⅎ᷈
ⱫᴦԜᴥͼⱪꜝᴟꜞ᷅
ⱨⱱᴡᴒᴟͼᴡⱳᴒͼꜞᴟᴒᴐᴒᴑ꞉ꜜⱲͼꜞᴟꜝᴐᴒᴑᴢᴟᴒᴠͼԜꜜᴑͼԜᴠᴠᴒᴠᴠꜛᴒꜜᴡᴠͼԜᴟᴒͼᴐꜝꜛꜞꞌᴒᴡᴒᴑⱡ
ᶄ
ⱨᴑꜛ꞉ꜜ꞉ᴠᴡᴒᴟͼⱷꜚ͟ͼӿᴀᴒᴐᴡ꞉ꜝꜜͼ⅍᷅᷈᷾Ԑ
ⱨⱱᴡᴒᴟͼԜᴑꜛ꞉ꜜ꞉ᴠᴡᴟԜᴡ꞉ꜝꜜͼꜝⱱͼⱷꜚ͟ԓͼᴡⱳᴒͼⱱꜝꞌꞌꜝᴤ꞉ꜜⱲͼꜞꜝᴠᴡͼᴡᴟᴒԜᴡꜛᴒꜜᴡͼꜞᴟꜝᴐᴒᴑᴢᴟᴒᴠͼԜꜜᴑͼԜᴠᴠᴒᴠᴠꜛᴒꜜᴡᴠͼᴤ꞉ꞌꞌͼԝᴒͼ
ꜞᴒᴟⱱꜝᴟꜛᴒᴑⱡ
ᶄ
ᴃ꞉ᴡԜꞌͼᴠ꞉Ⱳꜜᴠͼ꞉ꜜᴐꞌᴢᴑ꞉ꜜⱲͼԝꜝᴑᴦͼᴡᴒꜛꜞᴒᴟԜᴡᴢᴟᴒԓͼⱶϸԓͼⱩ͟ͼԜꜜᴑͼϸϸͼӿᴀᴒᴐᴡ꞉ꜝꜜͼ⅍᷿᷅ԐͼԜᴡͼ᷈ͼԜꜜᴑͼ᷉ⱳꜝᴢᴟᴠͼꜞꜝᴠᴡ᷄
ᴑꜝᴠᴒ᷅ͼᴁⱳ꞉ᴠͼ᷉ͼⱳꜝᴢᴟͼԜᴠᴠᴒᴠᴠꜛᴒꜜᴡͼꜝⱱͼᴣ꞉ᴡԜꞌᴠͼꜛԜᴦͼԝᴒͼᴑ꞉ᴠꜛ꞉ᴠᴠᴒᴑͼ꞉ⱱԓͼԝԜᴠᴒᴑͼꜝꜜͼᴡⱳᴒͼᴑ꞉ᴠᴐᴟᴒᴡ꞉ꜝꜜͼꜝⱱͼᴡⱳᴒͼ
ⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟͼԜꜜᴑͼᴡⱳᴒͼԜԝᴠᴒꜜᴐᴒͼꜝⱱͼᴠԜⱱᴒᴡᴦͼᴠ꞉ⱲꜜԜꞌᴠԓͼᴡⱳᴒͼⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟͼᴑᴒᴡᴒᴟꜛ꞉ꜜᴒᴠͼᴡⱳԜᴡͼᴡⱳᴒͼᴠᴢԝ꞊ᴒᴐᴡͼ
ꜝꜜꞌᴦͼꜜᴒᴒᴑᴠͼᴡꜝͼԝᴒͼꜛꜝꜜ꞉ᴡꜝᴟᴒᴑͼⱱꜝᴟͼ᷈ͼⱳꜝᴢᴟͼꜞꜝᴠᴡͼᴑꜝᴠᴒ᷅ͼᴁⱳᴒͼꜞꜝᴠᴡ᷄ᴑꜝᴠᴒͼꜛꜝꜜ꞉ᴡꜝᴟ꞉ꜜⱲͼꜞᴒᴟ꞉ꜝᴑͼꜛԜᴦͼԝᴒͼ
ꞌᴒꜜⱲᴡⱳᴒꜜᴒᴑͼԝԜᴐꞋͼᴡꜝͼ᷉ͼⱳꜝᴢᴟᴠͼԜᴡͼԜꜜᴦͼᴡ꞉ꜛᴒͼԝᴦͼᴡⱳᴒͼᴀꜞꜝꜜᴠꜝᴟͼԝԜᴠᴒᴑͼꜝꜜͼⱫᴀꜚⱩͼᴟᴒᴐꜝꜛꜛᴒꜜᴑԜᴡ꞉ꜝꜜ᷅
ᶄ
ⱪꜝꜜᴐꜝꜛ꞉ᴡԜꜜᴡͼᴡⱳᴒᴟԜꜞᴦͼӿᴀᴒᴐᴡ꞉ꜝꜜͼ⅍᷅᷈᷉Ԑ
ᶄ
ⱨⱬͼᴐꜝꞌꞌᴒᴐᴡ꞉ꜝꜜͼӿᴀᴒᴐᴡ꞉ꜝꜜͼ⅍᷅᷈⅍Ԑ
7.9
Continuation of Treatment Period: Visits 6 and 7, Doses 6 and 7 
(Days 70 and 84, All ±3 Days)
꜡ꜜͼⱫԜᴦᴠͼⅎ᷇ͼԜꜜᴑͼ˲᷾ԓͼᴡⱳᴒͼⱱꜝꞌꞌꜝᴤ꞉ꜜⱲͼꜞᴟꜝᴐᴒᴑᴢᴟᴒᴠͼԜꜜᴑͼԜᴠᴠᴒᴠᴠꜛᴒꜜᴡᴠͼᴤ꞉ꞌꞌͼԝᴒͼꜞᴒᴟⱱꜝᴟꜛᴒᴑͼꜞᴟ꞉ꜝᴟͼᴡꜝͼⱷꜚ͟ͼ
Ԝᴑꜛ꞉ꜜ꞉ᴠᴡᴟԜᴡ꞉ꜝꜜⱡ
ᶄ
ᴃ꞉ᴡԜꞌͼᴠ꞉Ⱳꜜᴠͼ꞉ꜜᴐꞌᴢᴑ꞉ꜜⱲͼԝꜝᴑᴦͼᴡᴒꜛꜞᴒᴟԜᴡᴢᴟᴒԓͼⱶϸԓͼⱩ͟ͼԜꜜᴑͼϸϸͼӿᴀᴒᴐᴡ꞉ꜝꜜ⅍᷿᷅Ԑ
ᶄ
ⱪꜝꜜᴐꜝꜛ꞉ᴡԜꜜᴡͼᴡⱳᴒᴟԜꜞᴦͼӿᴀᴒᴐᴡ꞉ꜝꜜͼ⅍᷅᷈᷉Ԑ
ᶄ
ⱶⱨⱬͼԜᴡᴡԜᴐꞋͼ꞉ꜜⱱꜝᴟꜛԜᴡ꞉ꜝꜜͼӿᴀᴒᴐᴡ꞉ꜝꜜͼ⅍᷅᷾Ԑ
ᶄ
ⱨⱬͼᴐꜝꞌꞌᴒᴐᴡ꞉ꜝꜜͼӿᴀᴒᴐᴡ꞉ꜝꜜͼ⅍᷅᷈⅍Ԑ
ⱨⱱᴡᴒᴟͼᴡⱳᴒͼꜞᴟᴒᴐᴒᴑ꞉ꜜⱲͼꜞᴟꜝᴐᴒᴑᴢᴟᴒᴠͼԜꜜᴑͼԜᴠᴠᴒᴠᴠꜛᴒꜜᴡᴠͼԜᴟᴒͼᴐꜝꜛꜞꞌᴒᴡᴒᴑⱡ
ᶄ
ⱨᴑꜛ꞉ꜜ꞉ᴠᴡᴒᴟͼⱷꜚ͟ͼӿᴀᴒᴐᴡ꞉ꜝꜜͼ⅍᷅᷈᷾Ԑ
ⱨⱱᴡᴒᴟͼԜᴑꜛ꞉ꜜ꞉ᴠᴡᴟԜᴡ꞉ꜝꜜͼꜝⱱͼⱷꜚ͟ԓͼᴡⱳᴒͼⱱꜝꞌꞌꜝᴤ꞉ꜜⱲͼꜞꜝᴠᴡͼᴡᴟᴒԜᴡꜛᴒꜜᴡͼꜞᴟꜝᴐᴒᴑᴢᴟᴒᴠͼԜꜜᴑͼԜᴠᴠᴒᴠᴠꜛᴒꜜᴡᴠͼᴤ꞉ꞌꞌͼԝᴒͼ
ꜞᴒᴟⱱꜝᴟꜛᴒᴑⱡ
ᶄ
ᴃ꞉ᴡԜꞌͼᴠ꞉Ⱳꜜᴠͼ꞉ꜜᴐꞌᴢᴑ꞉ꜜⱲͼԝꜝᴑᴦͼᴡᴒꜛꜞᴒᴟԜᴡᴢᴟᴒԓͼⱶϸԓͼⱩ͟ͼԜꜜᴑͼϸϸͼӿᴀᴒᴐᴡ꞉ꜝꜜͼ⅍᷿᷅ԐͼԜᴡͼ᷈ͼԜꜜᴑͼ᷉ⱳꜝᴢᴟᴠͼꜞꜝᴠᴡ᷄
ᴑꜝᴠᴒ᷅ͼᴁⱳ꞉ᴠͼ᷉ͼⱳꜝᴢᴟͼԜᴠᴠᴒᴠᴠꜛᴒꜜᴡͼꜝⱱͼᴣ꞉ᴡԜꞌᴠͼꜛԜᴦͼԝᴒͼᴑ꞉ᴠꜛ꞉ᴠᴠᴒᴑͼ꞉ⱱԓͼԝԜᴠᴒᴑͼꜝꜜͼᴡⱳᴒͼᴑ꞉ᴠᴐᴟᴒᴡ꞉ꜝꜜͼꜝⱱͼᴡⱳᴒͼ
ⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟͼԜꜜᴑͼᴡⱳᴒͼԜԝᴠᴒꜜᴐᴒͼꜝⱱͼᴠԜⱱᴒᴡᴦͼᴠ꞉ⱲꜜԜꞌᴠԓͼᴡⱳᴒͼⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟͼᴑᴒᴡᴒᴟꜛ꞉ꜜᴒᴠᴡⱳԜᴡͼᴡⱳᴒͼᴠᴢԝ꞊ᴒᴐᴡͼ
ꜝꜜꞌᴦͼꜜᴒᴒᴑᴠͼᴡꜝͼԝᴒͼꜛꜝꜜ꞉ᴡꜝᴟᴒᴑͼⱱꜝᴟͼ᷈ͼⱳꜝᴢᴟͼꜞꜝᴠᴡͼᴑꜝᴠᴒ᷅ͼᴁⱳᴒͼꜞꜝᴠᴡ᷄ᴑꜝᴠᴒͼꜛꜝꜜ꞉ᴡꜝᴟ꞉ꜜⱲͼꜞᴒᴟ꞉ꜝᴑͼꜛԜᴦͼԝᴒͼ
ꞌᴒꜜⱲᴡⱳᴒꜜᴒᴑͼԝԜᴐꞋͼᴡꜝͼ᷉ͼⱳꜝᴢᴟᴠͼԜᴡͼԜꜜᴦͼᴡ꞉ꜛᴒͼԝᴦͼᴡⱳᴒͼᴀꜞꜝꜜᴠꜝᴟͼԝԜᴠᴒᴑͼꜝꜜͼⱫᴀꜚⱩͼᴟᴒᴐꜝꜛꜛᴒꜜᴑԜᴡ꞉ꜝꜜ᷅
ᶄ
ⱪꜝꜜᴐꜝꜛ꞉ᴡԜꜜᴡͼᴡⱳᴒᴟԜꜞᴦͼӿᴀᴒᴐᴡ꞉ꜝꜜͼ⅍᷅᷈᷉Ԑ

Ⱬᴅ᷄᷉Ⱡ᷊᷇
ⱪꞌ꞉ꜜ꞉ᴐԜꞌͼᴁᴟ꞉Ԝꞌͼ͟ᴟꜝᴡꜝᴐꜝꞌⱡͼⱫᴅ᷄᷉Ⱡ᷊᷊᷇᷄᷇
ⱨꜛᴒꜜᴑꜛᴒꜜᴡͼ᷊᷅᷇ͼⱴ꞉ꜜԜꞌⱡͼ᷇ⱠͼꜗԜꜜᴢԜᴟᴦ᷉᷇᷈ⅎ
ⱪꜝꜜⱱ꞉ᴑᴒꜜᴡ꞉Ԝꞌ
͟ԜⱲᴒͼⅎ᷉
ⱫᴦԜᴥͼⱪꜝᴟꜞ᷅
ᶄ
ⱨⱬͼᴐꜝꞌꞌᴒᴐᴡ꞉ꜝꜜͼӿᴀᴒᴐᴡ꞉ꜝꜜͼ⅍᷅᷈⅍Ԑ
7.10
Continuation of Treatment Period: Visit 8, Dose 8 (Day 98±3 Days)
꜡ꜜͼⱫԜᴦͼⱠ˲ԓͼᴡⱳᴒͼⱱꜝꞌꞌꜝᴤ꞉ꜜⱲͼꜞᴟꜝᴐᴒᴑᴢᴟᴒᴠͼԜꜜᴑͼԜᴠᴠᴒᴠᴠꜛᴒꜜᴡᴠͼᴤ꞉ꞌꞌͼԝᴒͼꜞᴒᴟⱱꜝᴟꜛᴒᴑͼꜞᴟ꞉ꜝᴟͼᴡꜝͼⱷꜚ͟ͼ
Ԝᴑꜛ꞉ꜜ꞉ᴠᴡᴟԜᴡ꞉ꜝꜜⱡ
ᶄ
ᴃ꞉ᴡԜꞌͼᴠ꞉Ⱳꜜᴠͼ꞉ꜜᴐꞌᴢᴑ꞉ꜜⱲͼԝꜝᴑᴦͼᴡᴒꜛꜞᴒᴟԜᴡᴢᴟᴒԓͼⱶϸԓͼⱩ͟ͼԜꜜᴑͼϸϸͼӿᴀᴒᴐᴡ꞉ꜝꜜ⅍᷿᷅Ԑ
ᶄ
ⱪꜝꜛꜞꞌᴒᴡᴒͼꜞⱳᴦᴠ꞉ᴐԜꞌͼᴒᴥԜꜛ꞉ꜜԜᴡ꞉ꜝꜜͼӿᴀᴒᴐᴡ꞉ꜝꜜͼ⅍᷅⅍Ԑ
ᶄ
ꜙԜԝꜝᴟԜᴡꜝᴟᴦͼᴡᴒᴠᴡ꞉ꜜⱲͼ꞉ꜜᴐꞌᴢᴑ꞉ꜜⱲͼⱳᴒꜛԜᴡꜝꞌꜝⱲᴦԓͼᴐꜝԜⱲᴢꞌԜᴡ꞉ꜝꜜԓͼᴠᴒᴟᴢꜛͼᴐⱳᴒꜛ꞉ᴠᴡᴟᴦͼԜꜜᴑͼᴢᴟ꞉ꜜԜꞌᴦᴠ꞉ᴠͼ
ӿᴀᴒᴐᴡ꞉ꜝꜜͼ⅍᷅˲Ԑ
ᶄ
͟ᴟᴒⱲꜜԜꜜᴐᴦͼᴡᴒᴠᴡԓͼᴠᴒᴟᴢꜛͼꜝᴟͼᴢᴟ꞉ꜜᴒͼӿⱱᴒꜛԜꞌᴒᴠԐͼӿᴀᴒᴐᴡ꞉ꜝꜜͼ⅍᷅˲Ԑ
ᶄ
͟ꜘͼᴠԜꜛꜞꞌᴒͼᴐꜝꞌꞌᴒᴐᴡ꞉ꜝꜜͼӿᴀᴒᴐᴡ꞉ꜝꜜͼ⅍᷅ⱠԐ
ᶄ
͟ⱫͼᴠԜꜛꜞꞌᴒͼᴐꜝꞌꞌᴒᴐᴡ꞉ꜝꜜͼӿᴀᴒᴐᴡ꞉ꜝꜜͼ⅍᷅᷈᷇Ԑ
ᶄ
ⱨꜜᴡ꞉᷄ᴑᴟᴢⱲͼԜꜜᴡ꞉ԝꜝᴑᴦͼᴠԜꜛꜞꞌᴒͼᴐꜝꞌꞌᴒᴐᴡ꞉ꜝꜜͼӿᴀᴒᴐᴡ꞉ꜝꜜͼ⅍᷅᷈᷈Ԑ
ᶄ
ⱪꜝꜜᴐꜝꜛ꞉ᴡԜꜜᴡͼᴡⱳᴒᴟԜꜞᴦͼӿᴀᴒᴐᴡ꞉ꜝꜜͼ⅍᷅᷈᷉Ԑ
ᶄ
ⱶⱨⱬͼԜᴡᴡԜᴐꞋͼ꞉ꜜⱱꜝᴟꜛԜᴡ꞉ꜝꜜͼӿᴀᴒᴐᴡ꞉ꜝꜜͼ⅍᷅᷾Ԑ
ᶄ
ⱨⱬͼᴐꜝꞌꞌᴒᴐᴡ꞉ꜝꜜͼӿᴀᴒᴐᴡ꞉ꜝꜜͼ⅍᷅᷈⅍Ԑ
ᶄ
ϷᴢԜꞌ꞉ᴡᴦͼꜝⱱͼꞌ꞉ⱱᴒͼԜᴠᴠᴒᴠᴠꜛᴒꜜᴡᴠⱡͼⱬϷ᷿ⱫͼԜꜜᴑͼⱨⱬ᷄Ϸꜝꜙͼӿᴀᴒᴐᴡ꞉ꜝꜜͼ⅍᷿᷅᷈Ԑ
ⱨⱱᴡᴒᴟͼᴡⱳᴒͼꜞᴟᴒᴐᴒᴑ꞉ꜜⱲͼꜞᴟꜝᴐᴒᴑᴢᴟᴒᴠͼԜꜜᴑͼԜᴠᴠᴒᴠᴠꜛᴒꜜᴡᴠͼԜᴟᴒͼᴐꜝꜛꜞꞌᴒᴡᴒᴑⱡ
ᶄ
ⱨᴑꜛ꞉ꜜ꞉ᴠᴡᴒᴟͼⱷꜚ͟ͼӿᴀᴒᴐᴡ꞉ꜝꜜͼ⅍᷅᷈᷾Ԑ
ⱨⱱᴡᴒᴟͼԜᴑꜛ꞉ꜜ꞉ᴠᴡᴟԜᴡ꞉ꜝꜜͼꜝⱱͼⱷꜚ͟ԓͼᴡⱳᴒͼⱱꜝꞌꞌꜝᴤ꞉ꜜⱲͼꜞꜝᴠᴡͼᴡᴟᴒԜᴡꜛᴒꜜᴡͼꜞᴟꜝᴐᴒᴑᴢᴟᴒᴠͼԜꜜᴑͼԜᴠᴠᴒᴠᴠꜛᴒꜜᴡᴠͼᴤ꞉ꞌꞌͼԝᴒͼ
ꜞᴒᴟⱱꜝᴟꜛᴒᴑⱡ
ᶄ
ᴃ꞉ᴡԜꞌͼᴠ꞉Ⱳꜜᴠͼ꞉ꜜᴐꞌᴢᴑ꞉ꜜⱲͼԝꜝᴑᴦͼᴡᴒꜛꜞᴒᴟԜᴡᴢᴟᴒԓͼⱶϸԓͼⱩ͟ͼԜꜜᴑͼϸϸͼӿᴀᴒᴐᴡ꞉ꜝꜜͼ⅍᷿᷅ԐͼԜᴡͼ᷈ͼԜꜜᴑͼ᷉ⱳꜝᴢᴟᴠͼꜞꜝᴠᴡ᷄
ᴑꜝᴠᴒ᷅ͼᴁⱳ꞉ᴠͼ᷉ͼⱳꜝᴢᴟͼԜᴠᴠᴒᴠᴠꜛᴒꜜᴡͼꜝⱱͼᴣ꞉ᴡԜꞌᴠͼꜛԜᴦͼԝᴒͼᴑ꞉ᴠꜛ꞉ᴠᴠᴒᴑͼ꞉ⱱԓͼԝԜᴠᴒᴑͼꜝꜜͼᴡⱳᴒͼᴑ꞉ᴠᴐᴟᴒᴡ꞉ꜝꜜͼꜝⱱͼᴡⱳᴒͼ
ⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟͼԜꜜᴑͼᴡⱳᴒͼԜԝᴠᴒꜜᴐᴒͼꜝⱱͼᴠԜⱱᴒᴡᴦͼᴠ꞉ⱲꜜԜꞌᴠԓͼᴡⱳᴒͼⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟͼᴑᴒᴡᴒᴟꜛ꞉ꜜᴒᴠͼᴡⱳԜᴡͼᴡⱳᴒͼᴠᴢԝ꞊ᴒᴐᴡͼ
ꜝꜜꞌᴦͼꜜᴒᴒᴑᴠͼᴡꜝͼԝᴒͼꜛꜝꜜ꞉ᴡꜝᴟᴒᴑͼⱱꜝᴟͼ᷈ͼⱳꜝᴢᴟͼꜞꜝᴠᴡͼᴑꜝᴠᴒ᷅ͼᴁⱳᴒͼꜞꜝᴠᴡ᷄ᴑꜝᴠᴒͼꜛꜝꜜ꞉ᴡꜝᴟ꞉ꜜⱲͼꜞᴒᴟ꞉ꜝᴑͼꜛԜᴦͼԝᴒͼ
ꞌᴒꜜⱲᴡⱳᴒꜜᴒᴑͼԝԜᴐꞋͼᴡꜝͼ᷉ͼⱳꜝᴢᴟᴠͼԜᴡͼԜꜜᴦͼᴡ꞉ꜛᴒͼԝᴦͼᴡⱳᴒͼᴀꜞꜝꜜᴠꜝᴟͼԝԜᴠᴒᴑͼꜝꜜͼⱫᴀꜚⱩͼᴟᴒᴐꜝꜛꜛᴒꜜᴑԜᴡ꞉ꜝꜜ᷅
ᶄ
ⱪꜝꜜᴐꜝꜛ꞉ᴡԜꜜᴡͼᴡⱳᴒᴟԜꜞᴦͼӿᴀᴒᴐᴡ꞉ꜝꜜͼ⅍᷅᷈᷉Ԑ
ᶄ
ⱨⱬͼᴐꜝꞌꞌᴒᴐᴡ꞉ꜝꜜͼӿᴀᴒᴐᴡ꞉ꜝꜜͼ⅍᷅᷈⅍Ԑ

Ⱬᴅ᷄᷉Ⱡ᷊᷇
ⱪꞌ꞉ꜜ꞉ᴐԜꞌͼᴁᴟ꞉Ԝꞌͼ͟ᴟꜝᴡꜝᴐꜝꞌⱡͼⱫᴅ᷄᷉Ⱡ᷊᷊᷇᷄᷇
ⱨꜛᴒꜜᴑꜛᴒꜜᴡͼ᷊᷅᷇ͼⱴ꞉ꜜԜꞌⱡͼ᷇ⱠͼꜗԜꜜᴢԜᴟᴦ᷉᷇᷈ⅎ
ⱪꜝꜜⱱ꞉ᴑᴒꜜᴡ꞉Ԝꞌ
͟ԜⱲᴒͼⅎ᷊
ⱫᴦԜᴥͼⱪꜝᴟꜞ᷅
7.11
Continuation of Treatment Period: Visits 9 and 10, Doses 9 and 10 
(Days 112 and 126, All ±3 Days)
꜡ꜜͼⱫԜᴦᴠͼ᷈᷈᷉ͼԜꜜᴑͼ᷈᷉⅍ԓͼᴡⱳᴒͼⱱꜝꞌꞌꜝᴤ꞉ꜜⱲͼꜞᴟꜝᴐᴒᴑᴢᴟᴒᴠͼԜꜜᴑͼԜᴠᴠᴒᴠᴠꜛᴒꜜᴡᴠͼᴤ꞉ꞌꞌͼԝᴒͼꜞᴒᴟⱱꜝᴟꜛᴒᴑͼꜞᴟ꞉ꜝᴟͼᴡꜝͼⱷꜚ͟ͼ
Ԝᴑꜛ꞉ꜜ꞉ᴠᴡᴟԜᴡ꞉ꜝꜜⱡ
ᶄ
ᴃ꞉ᴡԜꞌͼᴠ꞉Ⱳꜜᴠͼ꞉ꜜᴐꞌᴢᴑ꞉ꜜⱲͼԝꜝᴑᴦͼᴡᴒꜛꜞᴒᴟԜᴡᴢᴟᴒԓͼⱶϸԓͼⱩ͟ͼԜꜜᴑͼϸϸͼӿᴀᴒᴐᴡ꞉ꜝꜜͼ⅍᷿᷅Ԑ
ᶄ
͟ᴟᴒⱲꜜԜꜜᴐᴦͼᴡᴒᴠᴡԓͼᴠᴒᴟᴢꜛͼꜝᴟͼᴢᴟ꞉ꜜᴒͼӿⱱᴒꜛԜꞌᴒᴠԐͼꜝꜜͼⱫԜᴦ᷈᷉⅍ᶐ᷊ͼӿᴀᴒᴐᴡ꞉ꜝꜜͼ⅍᷅˲Ԑ
ᶄ
ⱪꜝꜜᴐꜝꜛ꞉ᴡԜꜜᴡͼᴡⱳᴒᴟԜꜞᴦӿᴀᴒᴐᴡ꞉ꜝꜜͼ⅍᷅᷈᷉Ԑ
ᶄ
ⱶⱨⱬͼԜᴡᴡԜᴐꞋͼ꞉ꜜⱱꜝᴟꜛԜᴡ꞉ꜝꜜͼӿᴀᴒᴐᴡ꞉ꜝꜜͼ⅍᷅᷾Ԑ
ᶄ
ⱨⱬͼᴐꜝꞌꞌᴒᴐᴡ꞉ꜝꜜͼӿᴀᴒᴐᴡ꞉ꜝꜜͼ⅍᷅᷈⅍Ԑ
ᶄ
ϷᴢԜꞌ꞉ᴡᴦͼꜝⱱͼꞌ꞉ⱱᴒͼԜᴠᴠᴒᴠᴠꜛᴒꜜᴡᴠⱡͼⱨⱬ᷄ϷꜝꜙͼꜝꜜͼⱫԜᴦͼ᷈᷉⅍ᶐ᷊ͼӿᴀᴒᴐᴡ꞉ꜝꜜ⅍᷿᷅᷈Ԑ
ⱨⱱᴡᴒᴟͼᴡⱳᴒͼꜞᴟᴒᴐᴒᴑ꞉ꜜⱲͼꜞᴟꜝᴐᴒᴑᴢᴟᴒᴠͼԜꜜᴑͼԜᴠᴠᴒᴠᴠꜛᴒꜜᴡᴠͼԜᴟᴒͼᴐꜝꜛꜞꞌᴒᴡᴒᴑⱡ
ᶄ
ⱨᴑꜛ꞉ꜜ꞉ᴠᴡᴒᴟͼⱷꜚ͟ͼӿᴀᴒᴐᴡ꞉ꜝꜜͼ⅍᷅᷈᷾Ԑ
ⱨⱱᴡᴒᴟͼԜᴑꜛ꞉ꜜ꞉ᴠᴡᴟԜᴡ꞉ꜝꜜͼꜝⱱͼⱷꜚ͟ԓͼᴡⱳᴒͼⱱꜝꞌꞌꜝᴤ꞉ꜜⱲͼꜞꜝᴠᴡͼᴡᴟᴒԜᴡꜛᴒꜜᴡͼꜞᴟꜝᴐᴒᴑᴢᴟᴒᴠͼԜꜜᴑͼԜᴠᴠᴒᴠᴠꜛᴒꜜᴡᴠͼᴤ꞉ꞌꞌͼԝᴒͼ
ꜞᴒᴟⱱꜝᴟꜛᴒᴑⱡ
ᶄ
ᴃ꞉ᴡԜꞌͼᴠ꞉Ⱳꜜᴠͼ꞉ꜜᴐꞌᴢᴑ꞉ꜜⱲͼԝꜝᴑᴦͼᴡᴒꜛꜞᴒᴟԜᴡᴢᴟᴒԓͼⱶϸԓͼⱩ͟ͼԜꜜᴑͼϸϸͼӿᴀᴒᴐᴡ꞉ꜝꜜͼ⅍᷿᷅ԐͼԜᴡͼ᷈ͼԜꜜᴑͼ᷉ⱳꜝᴢᴟᴠͼꜞꜝᴠᴡ᷄
ᴑꜝᴠᴒ᷅ͼᴁⱳ꞉ᴠͼ᷉ͼⱳꜝᴢᴟͼԜᴠᴠᴒᴠᴠꜛᴒꜜᴡͼꜝⱱͼᴣ꞉ᴡԜꞌᴠͼꜛԜᴦͼԝᴒͼᴑ꞉ᴠꜛ꞉ᴠᴠᴒᴑͼ꞉ⱱԓͼԝԜᴠᴒᴑͼꜝꜜͼᴡⱳᴒͼᴑ꞉ᴠᴐᴟᴒᴡ꞉ꜝꜜͼꜝⱱͼᴡⱳᴒͼ
ⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟͼԜꜜᴑͼᴡⱳᴒͼԜԝᴠᴒꜜᴐᴒͼꜝⱱͼᴠԜⱱᴒᴡᴦͼᴠ꞉ⱲꜜԜꞌᴠԓͼᴡⱳᴒͼⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟͼᴑᴒᴡᴒᴟꜛ꞉ꜜᴒᴠͼᴡⱳԜᴡͼᴡⱳᴒͼᴠᴢԝ꞊ᴒᴐᴡͼ
ꜝꜜꞌᴦͼꜜᴒᴒᴑᴠͼᴡꜝͼԝᴒͼꜛꜝꜜ꞉ᴡꜝᴟᴒᴑͼⱱꜝᴟͼ᷈ͼⱳꜝᴢᴟͼꜞꜝᴠᴡͼᴑꜝᴠᴒ᷅ͼᴁⱳᴒͼꜞꜝᴠᴡ᷄ᴑꜝᴠᴒͼꜛꜝꜜ꞉ᴡꜝᴟ꞉ꜜⱲͼꜞᴒᴟ꞉ꜝᴑͼꜛԜᴦͼԝᴒͼ
ꞌᴒꜜⱲᴡⱳᴒꜜᴒᴑͼԝԜᴐꞋͼᴡꜝͼ᷉ͼⱳꜝᴢᴟᴠͼԜᴡͼԜꜜᴦͼᴡ꞉ꜛᴒͼԝᴦͼᴡⱳᴒͼᴀꜞꜝꜜᴠꜝᴟͼԝԜᴠᴒᴑͼꜝꜜⱫᴀꜚⱩͼᴟᴒᴐꜝꜛꜛᴒꜜᴑԜᴡ꞉ꜝꜜ᷅
ᶄ
ⱪꜝꜜᴐꜝꜛ꞉ᴡԜꜜᴡͼᴡⱳᴒᴟԜꜞᴦͼӿᴀᴒᴐᴡ꞉ꜝꜜͼ⅍᷅᷈᷉Ԑ
ᶄ
ⱨⱬͼᴐꜝꞌꞌᴒᴐᴡ꞉ꜝꜜͼӿᴀᴒᴐᴡ꞉ꜝꜜͼ⅍᷅᷈⅍Ԑ
7.12
Continuation of Treatment Period: Visit 11, Dose 11 (Day 140±3 Days)
꜡ꜜͼⱫԜᴦͼ᷈᷾᷇ԓͼᴡⱳᴒͼⱱꜝꞌꞌꜝᴤ꞉ꜜⱲͼꜞᴟꜝᴐᴒᴑᴢᴟᴒᴠͼԜꜜᴑͼԜᴠᴠᴒᴠᴠꜛᴒꜜᴡᴠͼᴤ꞉ꞌꞌͼԝᴒͼꜞᴒᴟⱱꜝᴟꜛᴒᴑͼꜞᴟ꞉ꜝᴟͼᴡꜝͼⱷꜚ͟ͼ
Ԝᴑꜛ꞉ꜜ꞉ᴠᴡᴟԜᴡ꞉ꜝꜜⱡ

ᴃ꞉ᴡԜꞌͼᴠ꞉Ⱳꜜᴠͼ꞉ꜜᴐꞌᴢᴑ꞉ꜜⱲͼԝꜝᴑᴦͼᴡᴒꜛꜞᴒᴟԜᴡᴢᴟᴒԓͼⱶϸԓͼⱩ͟ͼԜꜜᴑͼϸϸͼӿᴀᴒᴐᴡ꞉ꜝꜜͼ⅍᷿᷅Ԑ

ⱪꜝꜛꜞꞌᴒᴡᴒͼꜞⱳᴦᴠ꞉ᴐԜꞌͼᴒᴥԜꜛ꞉ꜜԜᴡ꞉ꜝꜜͼӿᴀᴒᴐᴡ꞉ꜝꜜͼ⅍᷅⅍Ԑ

ꜙԜԝꜝᴟԜᴡꜝᴟᴦͼᴡᴒᴠᴡ꞉ꜜⱲͼ꞉ꜜᴐꞌᴢᴑ꞉ꜜⱲͼⱳᴒꜛԜᴡꜝꞌꜝⱲᴦԓͼᴐꜝԜⱲᴢꞌԜᴡ꞉ꜝꜜԓͼᴠᴒᴟᴢꜛͼᴐⱳᴒꜛ꞉ᴠᴡᴟᴦͼԜꜜᴑͼᴢᴟ꞉ꜜԜꞌᴦᴠ꞉ᴠͼ
ӿᴀᴒᴐᴡ꞉ꜝꜜͼ⅍᷅˲Ԑ

͟ꜘͼᴠԜꜛꜞꞌᴒͼᴐꜝꞌꞌᴒᴐᴡ꞉ꜝꜜͼӿᴀᴒᴐᴡ꞉ꜝꜜͼ⅍᷅ⱠԐ

Ⱬᴅ᷄᷉Ⱡ᷊᷇
ⱪꞌ꞉ꜜ꞉ᴐԜꞌͼᴁᴟ꞉Ԝꞌͼ͟ᴟꜝᴡꜝᴐꜝꞌⱡͼⱫᴅ᷄᷉Ⱡ᷊᷊᷇᷄᷇
ⱨꜛᴒꜜᴑꜛᴒꜜᴡͼ᷊᷅᷇ͼⱴ꞉ꜜԜꞌⱡͼ᷇ⱠͼꜗԜꜜᴢԜᴟᴦ᷉᷇᷈ⅎ
ⱪꜝꜜⱱ꞉ᴑᴒꜜᴡ꞉Ԝꞌ
͟ԜⱲᴒͼⅎ᷾
ⱫᴦԜᴥͼⱪꜝᴟꜞ᷅

͟ⱫͼᴠԜꜛꜞꞌᴒͼᴐꜝꞌꞌᴒᴐᴡ꞉ꜝꜜͼӿᴀᴒᴐᴡ꞉ꜝꜜͼ⅍᷅᷈᷇Ԑ

ⱨꜜᴡ꞉᷄ᴑᴟᴢⱲͼԜꜜᴡ꞉ԝꜝᴑᴦͼᴠԜꜛꜞꞌᴒͼᴐꜝꞌꞌᴒᴐᴡ꞉ꜝꜜͼӿᴀᴒᴐᴡ꞉ꜝꜜͼ⅍᷅᷈᷈Ԑ

ⱪꜝꜜᴐꜝꜛ꞉ᴡԜꜜᴡͼᴡⱳᴒᴟԜꜞᴦͼӿᴀᴒᴐᴡ꞉ꜝꜜͼ⅍᷅᷈᷉Ԑ

ⱶⱨⱬͼԜᴡᴡԜᴐꞋͼ꞉ꜜⱱꜝᴟꜛԜᴡ꞉ꜝꜜͼӿᴀᴒᴐᴡ꞉ꜝꜜͼ⅍᷅᷾Ԑ

ⱨⱬͼᴐꜝꞌꞌᴒᴐᴡ꞉ꜝꜜͼӿᴀᴒᴐᴡ꞉ꜝꜜͼ⅍᷅᷈⅍Ԑ
ⱨⱱᴡᴒᴟͼᴡⱳᴒͼꜞᴟᴒᴐᴒᴑ꞉ꜜⱲͼꜞᴟꜝᴐᴒᴑᴢᴟᴒᴠͼԜꜜᴑͼԜᴠᴠᴒᴠᴠꜛᴒꜜᴡᴠͼԜᴟᴒͼᴐꜝꜛꜞꞌᴒᴡᴒᴑⱡ

ⱨᴑꜛ꞉ꜜ꞉ᴠᴡᴒᴟͼⱷꜚ͟ ӿᴀᴒᴐᴡ꞉ꜝꜜͼ⅍᷅᷈᷾Ԑ
ⱨⱱᴡᴒᴟͼԜᴑꜛ꞉ꜜ꞉ᴠᴡᴟԜᴡ꞉ꜝꜜͼꜝⱱͼⱷꜚ͟ԓͼᴡⱳᴒͼⱱꜝꞌꞌꜝᴤ꞉ꜜⱲͼꜞꜝᴠᴡͼᴡᴟᴒԜᴡꜛᴒꜜᴡͼꜞᴟꜝᴐᴒᴑᴢᴟᴒᴠͼԜꜜᴑͼԜᴠᴠᴒᴠᴠꜛᴒꜜᴡᴠͼᴤ꞉ꞌꞌͼԝᴒͼ
ꜞᴒᴟⱱꜝᴟꜛᴒᴑⱡ

ᴃ꞉ᴡԜꞌͼᴠ꞉Ⱳꜜᴠͼ꞉ꜜᴐꞌᴢᴑ꞉ꜜⱲͼԝꜝᴑᴦͼᴡᴒꜛꜞᴒᴟԜᴡᴢᴟᴒԓͼⱶϸԓͼⱩ͟ͼԜꜜᴑͼϸϸͼӿᴀᴒᴐᴡ꞉ꜝꜜͼ⅍᷿᷅ԐͼԜᴡͼ᷈ͼԜꜜᴑͼ᷉ⱳꜝᴢᴟᴠͼꜞꜝᴠᴡ᷄
ᴑꜝᴠᴒ᷅ͼᴁⱳ꞉ᴠͼ᷉ͼⱳꜝᴢᴟͼԜᴠᴠᴒᴠᴠꜛᴒꜜᴡͼꜝⱱͼᴣ꞉ᴡԜꞌᴠͼꜛԜᴦͼԝᴒͼᴑ꞉ᴠꜛ꞉ᴠᴠᴒᴑͼ꞉ⱱԓͼԝԜᴠᴒᴑͼꜝꜜͼᴡⱳᴒͼᴑ꞉ᴠᴐᴟᴒᴡ꞉ꜝꜜͼꜝⱱͼᴡⱳᴒͼ
ⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟͼԜꜜᴑͼᴡⱳᴒͼԜԝᴠᴒꜜᴐᴒͼꜝⱱͼᴠԜⱱᴒᴡᴦͼᴠ꞉ⱲꜜԜꞌᴠԓͼᴡⱳᴒͼⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟͼᴑᴒᴡᴒᴟꜛ꞉ꜜᴒᴠͼᴡⱳԜᴡͼᴡⱳᴒͼᴠᴢԝ꞊ᴒᴐᴡͼ
ꜝꜜꞌᴦͼꜜᴒᴒᴑᴠͼᴡꜝͼԝᴒͼꜛꜝꜜ꞉ᴡꜝᴟᴒᴑͼⱱꜝᴟͼ᷈ͼⱳꜝᴢᴟͼꜞꜝᴠᴡͼᴑꜝᴠᴒ᷅ͼᴁⱳᴒͼꜞꜝᴠᴡ᷄ᴑꜝᴠᴒͼꜛꜝꜜ꞉ᴡꜝᴟ꞉ꜜⱲͼꜞᴒᴟ꞉ꜝᴑͼꜛԜᴦͼԝᴒͼ
ꞌᴒꜜⱲᴡⱳᴒꜜᴒᴑͼԝԜᴐꞋͼᴡꜝͼ᷉ͼⱳꜝᴢᴟᴠͼԜᴡͼԜꜜᴦͼᴡ꞉ꜛᴒͼԝᴦͼᴡⱳᴒͼᴀꜞꜝꜜᴠꜝᴟͼԝԜᴠᴒᴑͼꜝꜜͼⱫᴀꜚⱩͼᴟᴒᴐꜝꜛꜛᴒꜜᴑԜᴡ꞉ꜝꜜ᷅

ⱪꜝꜜᴐꜝꜛ꞉ᴡԜꜜᴡͼᴡⱳᴒᴟԜꜞᴦͼӿᴀᴒᴐᴡ꞉ꜝꜜͼ⅍᷅᷈᷉Ԑ

ⱨⱬͼᴐꜝꞌꞌᴒᴐᴡ꞉ꜝꜜͼӿᴀᴒᴐᴡ꞉ꜝꜜͼ⅍᷅᷈⅍Ԑ
7.13
Continuation of Treatment Period (Day 144±1 Day)
ᴁⱳ꞉ᴠͼⱬⱪⱵͼԜᴠᴠᴒᴠᴠꜛᴒꜜᴡͼꜛԜᴦͼԝᴒͼᴐꜝꜜᴑᴢᴐᴡᴒᴑͼᴡⱳᴟꜝᴢⱲⱳͼԜꜜͼԜᴡ᷄ⱳꜝꜛᴒͼᴣ꞉ᴠ꞉ᴡͼԝᴦͼԜͼꜜᴢᴟᴠᴒͼꜝᴟͼᴡᴒᴐⱳꜜ꞉ᴐ꞉ԜꜜͼꜝᴟԜᴡͼ
ᴡⱳᴒͼᴠᴡᴢᴑᴦͼᴠ꞉ᴡᴒ᷅ͼᴁⱳᴒͼᴑԜᴡᴒԓͼᴡ꞉ꜛᴒͼԜꜜᴑͼᴐꜝꞌꞌᴒᴐᴡ꞉ꜝꜜͼꞌꜝᴐԜᴡ꞉ꜝꜜͼꜝⱱͼᴡⱳ꞉ᴠͼⱬⱪⱵͼԜꜜᴑͼ꞉ᴡᴠͼᴟᴒᴠᴢꞌᴡᴠͼᴤ꞉ꞌꞌͼԝᴒͼ
ᴑꜝᴐᴢꜛᴒꜜᴡᴒᴑͼ꞉ꜜͼᴡⱳᴒͼᴠꜝᴢᴟᴐᴒͼᴑꜝᴐᴢꜛᴒꜜᴡᴠͼԜꜜᴑͼᴒⱪϸⱴ᷅ͼ

᷈᷉᷄ꜙᴒԜᴑͼⱬⱪⱵͼӿᴀᴒᴐᴡ꞉ꜝꜜͼ⅍᷅ⅎԐ
7.14
Continuation of Treatment Period: Visits 12 and 13, Doses 12 and 13 
(Days 154 and 168, All ±3 Days)
꜡ꜜͼⱫԜᴦᴠͼ᷿᷈᷾ͼԜꜜᴑͼ᷈⅍˲ԓͼᴡⱳᴒͼⱱꜝꞌꞌꜝᴤ꞉ꜜⱲͼꜞᴟꜝᴐᴒᴑᴢᴟᴒᴠͼԜꜜᴑͼԜᴠᴠᴒᴠᴠꜛᴒꜜᴡᴠͼᴤ꞉ꞌꞌͼԝᴒͼꜞᴒᴟⱱꜝᴟꜛᴒᴑͼꜞᴟ꞉ꜝᴟͼᴡꜝͼⱷꜚ͟ͼ
Ԝᴑꜛ꞉ꜜ꞉ᴠᴡᴟԜᴡ꞉ꜝꜜⱡ

ᴃ꞉ᴡԜꞌͼᴠ꞉Ⱳꜜᴠͼ꞉ꜜᴐꞌᴢᴑ꞉ꜜⱲͼԝꜝᴑᴦͼᴡᴒꜛꜞᴒᴟԜᴡᴢᴟᴒԓͼⱶϸԓͼⱩ͟ͼԜꜜᴑͼϸϸͼӿᴀᴒᴐᴡ꞉ꜝꜜͼ⅍᷿᷅Ԑ

͟ᴟᴒⱲꜜԜꜜᴐᴦͼᴡᴒᴠᴡԓͼᴠᴒᴟᴢꜛͼꜝᴟͼᴢᴟ꞉ꜜᴒͼӿⱱᴒꜛԜꞌᴒᴠԐͼꜝꜜͼⱫԜᴦ᷿᷈᷾ᶐ᷊ͼӿᴀᴒᴐᴡ꞉ꜝꜜͼ⅍᷅˲Ԑ

ⱪꜝꜜᴐꜝꜛ꞉ᴡԜꜜᴡͼᴡⱳᴒᴟԜꜞᴦͼӿᴀᴒᴐᴡ꞉ꜝꜜͼ⅍᷅᷈᷉Ԑ

ⱶⱨⱬͼԜᴡᴡԜᴐꞋͼ꞉ꜜⱱꜝᴟꜛԜᴡ꞉ꜝꜜͼӿᴀᴒᴐᴡ꞉ꜝꜜͼ⅍᷅᷾Ԑ

ⱨⱬͼᴐꜝꞌꞌᴒᴐᴡ꞉ꜝꜜͼӿᴀᴒᴐᴡ꞉ꜝꜜͼ⅍᷅᷈⅍Ԑ

ϷᴢԜꞌ꞉ᴡᴦͼꜝⱱͼꞌ꞉ⱱᴒͼԜᴠᴠᴒᴠᴠꜛᴒꜜᴡᴠⱡͼⱨⱬ᷄ϷꜝꜙͼꜝꜜͼⱫԜᴦͼ᷿᷈᷾ᶐ᷊ͼӿᴀᴒᴐᴡ꞉ꜝꜜ⅍᷿᷅᷈Ԑ

Ⱬᴅ᷄᷉Ⱡ᷊᷇
ⱪꞌ꞉ꜜ꞉ᴐԜꞌͼᴁᴟ꞉Ԝꞌͼ͟ᴟꜝᴡꜝᴐꜝꞌⱡͼⱫᴅ᷄᷉Ⱡ᷊᷊᷇᷄᷇
ⱨꜛᴒꜜᴑꜛᴒꜜᴡͼ᷊᷅᷇ͼⱴ꞉ꜜԜꞌⱡͼ᷇ⱠͼꜗԜꜜᴢԜᴟᴦ᷉᷇᷈ⅎ
ⱪꜝꜜⱱ꞉ᴑᴒꜜᴡ꞉Ԝꞌ
͟ԜⱲᴒͼⅎ᷿
ⱫᴦԜᴥͼⱪꜝᴟꜞ᷅
ⱨⱱᴡᴒᴟͼᴡⱳᴒͼꜞᴟᴒᴐᴒᴑ꞉ꜜⱲͼꜞᴟꜝᴐᴒᴑᴢᴟᴒᴠͼԜꜜᴑͼԜᴠᴠᴒᴠᴠꜛᴒꜜᴡᴠͼԜᴟᴒͼᴐꜝꜛꜞꞌᴒᴡᴒᴑⱡ

ⱨᴑꜛ꞉ꜜ꞉ᴠᴡᴒᴟͼⱷꜚ͟ͼӿᴀᴒᴐᴡ꞉ꜝꜜͼ⅍᷅᷈᷾Ԑ
ⱨⱱᴡᴒᴟͼԜᴑꜛ꞉ꜜ꞉ᴠᴡᴟԜᴡ꞉ꜝꜜͼꜝⱱͼⱷꜚ͟ԓͼᴡⱳᴒͼⱱꜝꞌꞌꜝᴤ꞉ꜜⱲͼꜞꜝᴠᴡͼᴡᴟᴒԜᴡꜛᴒꜜᴡͼꜞᴟꜝᴐᴒᴑᴢᴟᴒᴠͼԜꜜᴑͼԜᴠᴠᴒᴠᴠꜛᴒꜜᴡᴠͼᴤ꞉ꞌꞌͼԝᴒͼ
ꜞᴒᴟⱱꜝᴟꜛᴒᴑⱡ

ᴃ꞉ᴡԜꞌͼᴠ꞉Ⱳꜜᴠͼ꞉ꜜᴐꞌᴢᴑ꞉ꜜⱲͼԝꜝᴑᴦͼᴡᴒꜛꜞᴒᴟԜᴡᴢᴟᴒԓͼⱶϸԓͼⱩ͟ͼԜꜜᴑͼϸϸͼӿᴀᴒᴐᴡ꞉ꜝꜜͼ⅍᷿᷅ԐͼԜᴡͼ᷈ͼԜꜜᴑͼ᷉ⱳꜝᴢᴟᴠͼꜞꜝᴠᴡ᷄
ᴑꜝᴠᴒ᷅ͼᴁⱳ꞉ᴠͼ᷉ͼⱳꜝᴢᴟͼԜᴠᴠᴒᴠᴠꜛᴒꜜᴡͼꜝⱱͼᴣ꞉ᴡԜꞌᴠͼꜛԜᴦͼԝᴒͼᴑ꞉ᴠꜛ꞉ᴠᴠᴒᴑͼ꞉ⱱԓ ԝԜᴠᴒᴑͼꜝꜜͼᴡⱳᴒͼᴑ꞉ᴠᴐᴟᴒᴡ꞉ꜝꜜͼꜝⱱͼᴡⱳᴒͼ
ⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟͼԜꜜᴑͼᴡⱳᴒͼԜԝᴠᴒꜜᴐᴒͼꜝⱱͼᴠԜⱱᴒᴡᴦͼᴠ꞉ⱲꜜԜꞌᴠԓͼᴡⱳᴒͼⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟͼᴑᴒᴡᴒᴟꜛ꞉ꜜᴒᴠͼᴡⱳԜᴡͼᴡⱳᴒͼᴠᴢԝ꞊ᴒᴐᴡͼ
ꜝꜜꞌᴦͼꜜᴒᴒᴑᴠͼᴡꜝͼԝᴒͼꜛꜝꜜ꞉ᴡꜝᴟᴒᴑͼⱱꜝᴟͼ᷈ͼⱳꜝᴢᴟͼꜞꜝᴠᴡͼᴑꜝᴠᴒ᷅ͼᴁⱳᴒͼꜞꜝᴠᴡ᷄ᴑꜝᴠᴒͼꜛꜝꜜ꞉ᴡꜝᴟ꞉ꜜⱲͼꜞᴒᴟ꞉ꜝᴑͼꜛԜᴦͼԝᴒͼ
ꞌᴒꜜⱲᴡⱳᴒꜜᴒᴑͼԝԜᴐꞋͼᴡꜝͼ᷉ͼⱳꜝᴢᴟᴠͼԜᴡͼԜꜜᴦͼᴡ꞉ꜛᴒͼԝᴦͼᴡⱳᴒͼᴀꜞꜝꜜᴠꜝᴟͼԝԜᴠᴒᴑͼꜝꜜͼⱫᴀꜚⱩͼᴟᴒᴐꜝꜛꜛᴒꜜᴑԜᴡ꞉ꜝꜜ᷅

ⱪꜝꜜᴐꜝꜛ꞉ᴡԜꜜᴡͼᴡⱳᴒᴟԜꜞᴦͼӿᴀᴒᴐᴡ꞉ꜝꜜͼ⅍᷅᷈᷉Ԑ

ⱨⱬͼᴐꜝꞌꞌᴒᴐᴡ꞉ꜝꜜͼӿᴀᴒᴐᴡ꞉ꜝꜜͼ⅍᷅᷈⅍Ԑ
7.15
Completion of Treatment Period: Visit 14, Day 182±3 Days
꜡ꜜͼⱫԜᴦͼ᷈˲᷉ԓͼᴡⱳᴒͼⱱꜝꞌꞌꜝᴤ꞉ꜜⱲͼꜞᴟꜝᴐᴒᴑᴢᴟᴒᴠͼԜꜜᴑͼԜᴠᴠᴒᴠᴠꜛᴒꜜᴡᴠͼᴤ꞉ꞌꞌͼԝᴒͼꜞᴒᴟⱱꜝᴟꜛᴒᴑⱡ

ᴃ꞉ᴡԜꞌͼᴠ꞉Ⱳꜜᴠͼ꞉ꜜᴐꞌᴢᴑ꞉ꜜⱲͼԝꜝᴑᴦͼᴡᴒꜛꜞᴒᴟԜᴡᴢᴟᴒԓͼⱶϸԓͼⱩ͟ͼԜꜜᴑͼϸϸͼӿᴀᴒᴐᴡ꞉ꜝꜜͼ⅍᷿᷅Ԑ

ⱪꜝꜛꜞꞌᴒᴡᴒͼꜞⱳᴦᴠ꞉ᴐԜꞌͼᴒᴥԜꜛ꞉ꜜԜᴡ꞉ꜝꜜͼӿᴀᴒᴐᴡ꞉ꜝꜜͼ⅍᷅⅍Ԑ

᷈᷉᷄ꜙᴒԜᴑͼⱬⱪⱵͼӿᴀᴒᴐᴡ꞉ꜝꜜͼ⅍᷅ⅎԐ

ꜙԜԝꜝᴟԜᴡꜝᴟᴦͼᴡᴒᴠᴡ꞉ꜜⱲͼ꞉ꜜᴐꞌᴢᴑ꞉ꜜⱲͼⱳᴒꜛԜᴡꜝꞌꜝⱲᴦԓͼᴐꜝԜⱲᴢꞌԜᴡ꞉ꜝꜜԓͼᴠᴒᴟᴢꜛͼᴐⱳᴒꜛ꞉ᴠᴡᴟᴦͼԜꜜᴑͼᴢᴟ꞉ꜜԜꞌᴦᴠ꞉ᴠͼ
ӿᴀᴒᴐᴡ꞉ꜝꜜͼ⅍᷅˲Ԑ

ᴂᴟ꞉ꜜᴒͼꜞᴟᴒⱲꜜԜꜜᴐᴦͼᴡᴒᴠᴡͼӿⱱᴒꜛԜꞌᴒᴠԐͼӿᴀᴒᴐᴡ꞉ꜝꜜͼ⅍᷅˲Ԑ

͟ꜘͼᴠԜꜛꜞꞌᴒͼᴐꜝꞌꞌᴒᴐᴡ꞉ꜝꜜͼӿᴀᴒᴐᴡ꞉ꜝꜜͼ⅍᷅ⱠԐ

͟ⱫͼᴠԜꜛꜞꞌᴒͼᴐꜝꞌꞌᴒᴐᴡ꞉ꜝꜜͼӿᴀᴒᴐᴡ꞉ꜝꜜͼ⅍᷅᷈᷇Ԑ

ⱨꜜᴡ꞉᷄ᴑᴟᴢⱲͼԜꜜᴡ꞉ԝꜝᴑᴦͼᴠԜꜛꜞꞌᴒͼᴐꜝꞌꞌᴒᴐᴡ꞉ꜝꜜͼӿᴀᴒᴐᴡ꞉ꜝꜜͼ⅍᷅᷈᷈Ԑ

ⱪꜝꜜᴐꜝꜛ꞉ᴡԜꜜᴡͼᴡⱳᴒᴟԜꜞᴦͼӿᴀᴒᴐᴡ꞉ꜝꜜͼ⅍᷅᷈᷉Ԑ

ⱶⱨⱬͼԜᴡᴡԜᴐꞋͼ꞉ꜜⱱꜝᴟꜛԜᴡ꞉ꜝꜜͼӿᴀᴒᴐᴡ꞉ꜝꜜͼ⅍᷅᷾Ԑ

ⱨⱬͼᴐꜝꞌꞌᴒᴐᴡ꞉ꜝꜜͼӿᴀᴒᴐᴡ꞉ꜝꜜͼ⅍᷅᷈⅍Ԑ

ϷᴢԜꞌ꞉ᴡᴦͼꜝⱱͼꞌ꞉ⱱᴒͼԜᴠᴠᴒᴠᴠꜛᴒꜜᴡᴠⱡͼⱬϷ᷿ⱫͼԜꜜᴑͼⱨⱬ᷄Ϸꜝꜙͼӿᴀᴒᴐᴡ꞉ꜝꜜͼ⅍᷿᷅᷈Ԑ

Ⱬ꞉ᴠᴐⱳԜᴟⱲᴒͼⱱᴟꜝꜛͼᴠᴡᴢᴑᴦⱡͼͼ

ᴀᴢԝ꞊ᴒᴐᴡᴠͼᴤ꞉ꞌꞌͼԝᴒͼꜝⱱⱱᴒᴟᴒᴑͼᴡⱳᴒͼꜝꜞᴡ꞉ꜝꜜͼꜝⱱͼᴒꜜᴟꜝꞌꞌ꞉ꜜⱲͼ꞉ꜜͼᴡⱳᴒͼⱫᴅ᷄᷉Ⱡ᷊᷇᷄᷇᷾ͼ꜡ꜞᴒꜜͼꜙԜԝᴒꞌͼⱬᴥᴡᴒꜜᴠ꞉ꜝꜜͼ
ӿ꜡ꜙⱬԐͼᴠᴡᴢᴑᴦͼⱱꜝᴟͼᴐꜝꜜᴡ꞉ꜜᴢᴒᴑͼᴡᴟᴒԜᴡꜛᴒꜜᴡͼԜꜜᴑͼᴠԜⱱᴒᴡᴦͼⱱꜝꞌꞌꜝᴤ᷄ᴢꜞ᷅ͼ

ⱷꜜⱱꜝᴟꜛᴒᴑͼⱪꜝꜜᴠᴒꜜᴡͼꜝԝᴡԜ꞉ꜜᴒᴑͼⱱꜝᴟͼᴠᴡᴢᴑᴦͼⱫᴅ᷄᷉Ⱡ᷊᷇᷄᷇᷾

Ⱬᴅ᷄᷉Ⱡ᷊᷇
ⱪꞌ꞉ꜜ꞉ᴐԜꞌͼᴁᴟ꞉Ԝꞌͼ͟ᴟꜝᴡꜝᴐꜝꞌⱡͼⱫᴅ᷄᷉Ⱡ᷊᷊᷇᷄᷇
ⱨꜛᴒꜜᴑꜛᴒꜜᴡͼ᷊᷅᷇ͼⱴ꞉ꜜԜꞌⱡͼ᷇ⱠͼꜗԜꜜᴢԜᴟᴦ᷉᷇᷈ⅎ
ⱪꜝꜜⱱ꞉ᴑᴒꜜᴡ꞉Ԝꞌ
͟ԜⱲᴒͼⅎ⅍
ⱫᴦԜᴥͼⱪꜝᴟꜞ᷅

ᴀᴢԝ꞊ᴒᴐᴡᴠͼᴤⱳꜝͼᴐꜝꜜᴠᴒꜜᴡͼᴡꜝͼꜞԜᴟᴡ꞉ᴐ꞉ꜞԜᴡᴒͼ꞉ꜜͼⱫᴅ᷄᷉Ⱡ᷊᷇᷄᷇᷾ͼᴤ꞉ꞌꞌͼᴟᴒᴐᴒ꞉ᴣᴒͼᴡⱳᴒ꞉ᴟͼⱱ꞉ᴟᴠᴡͼ꜡ꜙⱬͼᴑꜝᴠᴒͼ
ⱱꜝꞌꞌꜝᴤ꞉ꜜⱲͼᴡⱳᴒͼᴐꜝꜛꜞꞌᴒᴡ꞉ꜝꜜͼꜝⱱͼԜꞌꞌͼᴑꜝᴢԝꞌᴒ᷄ԝꞌ꞉ꜜᴑͼԜᴠᴠᴒᴠᴠꜛᴒꜜᴡᴠͼᴠᴐⱳᴒᴑᴢꞌᴒᴑͼꜝꜜͼⱫԜᴦͼ᷈˲᷉᷅ͼ
7.16
Follow-up Period (Subjects Not Continuing in Open-Label Extension 
Study): Visit 15, Day 210 ±3 Days

ᴃ꞉ᴡԜꞌͼᴠ꞉Ⱳꜜᴠͼ꞉ꜜᴐꞌᴢᴑ꞉ꜜⱲͼԝꜝᴑᴦͼᴡᴒꜛꜞᴒᴟԜᴡᴢᴟᴒԓͼⱶϸԓͼⱩ͟ͼԜꜜᴑͼϸϸͼӿᴀᴒᴐᴡ꞉ꜝꜜͼ⅍᷿᷅Ԑ

͟ꜘͼᴠԜꜛꜞꞌᴒͼᴐꜝꞌꞌᴒᴐᴡ꞉ꜝꜜͼӿᴀᴒᴐᴡ꞉ꜝꜜͼ⅍᷅ⱠԐ

͟ⱫͼᴠԜꜛꜞꞌᴒͼᴐꜝꞌꞌᴒᴐᴡ꞉ꜝꜜͼӿᴀᴒᴐᴡ꞉ꜝꜜͼ⅍᷅᷈᷇Ԑ

ⱪꜝꜜᴐꜝꜛ꞉ᴡԜꜜᴡͼᴡⱳᴒᴟԜꜞᴦͼӿᴀᴒᴐᴡ꞉ꜝꜜͼ⅍᷅᷈᷉Ԑ

ⱶⱨⱬͼԜᴡᴡԜᴐꞋͼ꞉ꜜⱱꜝᴟꜛԜᴡ꞉ꜝꜜͼӿᴀᴒᴐᴡ꞉ꜝꜜͼ⅍᷅᷾Ԑ

ⱨⱬͼᴐꜝꞌꞌᴒᴐᴡ꞉ꜝꜜͼӿᴀᴒᴐᴡ꞉ꜝꜜͼ⅍᷅᷈⅍Ԑ
7.17
Final Follow-up Visit (Subjects Not Continuing in Open-Label 
Extension Study): Visit 16, Day 238±3 Days

ᴃ꞉ᴡԜꞌͼᴠ꞉Ⱳꜜᴠͼ꞉ꜜᴐꞌᴢᴑ꞉ꜜⱲͼԝꜝᴑᴦͼᴡᴒꜛꜞᴒᴟԜᴡᴢᴟᴒԓͼⱶϸԓͼⱩ͟ͼԜꜜᴑͼϸϸͼӿᴀᴒᴐᴡ꞉ꜝꜜͼ⅍᷿᷅Ԑ

ⱪꜝꜛꜞꞌᴒᴡᴒͼꜞⱳᴦᴠ꞉ᴐԜꞌͼᴒᴥԜꜛ꞉ꜜԜᴡ꞉ꜝꜜͼӿᴀᴒᴐᴡ꞉ꜝꜜͼ⅍᷅⅍Ԑ

᷈᷉᷄ꜙᴒԜᴑͼⱬⱪⱵͼӿᴀᴒᴐᴡ꞉ꜝꜜͼ⅍᷅ⅎԐ

ꜙԜԝꜝᴟԜᴡꜝᴟᴦͼᴡᴒᴠᴡ꞉ꜜⱲͼ꞉ꜜᴐꞌᴢᴑ꞉ꜜⱲͼⱳᴒꜛԜᴡꜝꞌꜝⱲᴦԓͼᴐꜝԜⱲᴢꞌԜᴡ꞉ꜝꜜԓͼᴠᴒᴟᴢꜛͼᴐⱳᴒꜛ꞉ᴠᴡᴟᴦͼԜꜜᴑͼᴢᴟ꞉ꜜԜꞌᴦᴠ꞉ᴠͼ
ӿᴀᴒᴐᴡ꞉ꜝꜜͼ⅍᷅˲Ԑ

͟ᴟᴒⱲꜜԜꜜᴐᴦͼᴡᴒᴠᴡԓͼᴠᴒᴟᴢꜛͼꜝᴟͼᴢᴟ꞉ꜜᴒͼӿⱱᴒꜛԜꞌᴒᴠԐͼӿᴀᴒᴐᴡ꞉ꜝꜜͼ⅍᷅˲Ԑ

͟ꜘͼᴠԜꜛꜞꞌᴒͼᴐꜝꞌꞌᴒᴐᴡ꞉ꜝꜜͼӿᴀᴒᴐᴡ꞉ꜝꜜͼ⅍᷅ⱠԐ

͟ⱫͼᴠԜꜛꜞꞌᴒͼᴐꜝꞌꞌᴒᴐᴡ꞉ꜝꜜͼӿᴀᴒᴐᴡ꞉ꜝꜜͼ⅍᷅᷈᷇Ԑ

ⱨꜜᴡ꞉᷄ᴑᴟᴢⱲͼԜꜜᴡ꞉ԝꜝᴑᴦͼᴠԜꜛꜞꞌᴒͼᴐꜝꞌꞌᴒᴐᴡ꞉ꜝꜜͼӿᴀᴒᴐᴡ꞉ꜝꜜͼ⅍᷅᷈᷈Ԑ

ⱪꜝꜜᴐꜝꜛ꞉ᴡԜꜜᴡͼᴡⱳᴒᴟԜꜞᴦͼӿᴀᴒᴐᴡ꞉ꜝꜜͼ⅍᷅᷈᷉Ԑ

ⱶⱨⱬͼԜᴡᴡԜᴐꞋͼ꞉ꜜⱱꜝᴟꜛԜᴡ꞉ꜝꜜͼӿᴀᴒᴐᴡ꞉ꜝꜜͼ⅍᷅᷾Ԑ

ⱨⱬͼᴐꜝꞌꞌᴒᴐᴡ꞉ꜝꜜͼӿᴀᴒᴐᴡ꞉ꜝꜜͼ⅍᷅᷈⅍Ԑ

ϷᴢԜꞌ꞉ᴡᴦͼꜝⱱͼꞌ꞉ⱱᴒͼԜᴠᴠᴒᴠᴠꜛᴒꜜᴡᴠⱡͼⱬϷ᷿ⱫͼԜꜜᴑͼⱨⱬ᷄Ϸꜝꜙͼӿᴀᴒᴐᴡ꞉ꜝꜜͼ⅍᷿᷅᷈Ԑ
7.18
Early Termination (ET)
ᴀᴢԝ꞊ᴒᴐᴡᴠͼᴡⱳԜᴡͼᴡᴒᴟꜛ꞉ꜜԜᴡᴒͼᴒԜᴟꞌᴦͼⱱᴟꜝꜛͼᴡⱳᴒͼᴠᴡᴢᴑᴦͼᴤ꞉ꞌꞌͼᴢꜜᴑᴒᴟⱲꜝͼӿ꞉ⱱͼꜞꜝᴠᴠ꞉ԝꞌᴒԐͼԜꞌꞌͼꜝⱱͼᴡⱳᴒͼԜᴠᴠᴒᴠᴠꜛᴒꜜᴡᴠͼԜꜜᴑͼ
ꜞᴟꜝᴐᴒᴑᴢᴟᴒᴠͼᴠᴐⱳᴒᴑᴢꞌᴒᴑͼⱱꜝᴟͼⱫԜᴦͼ᷈˲᷉᷅

Ⱬᴅ᷄᷉Ⱡ᷊᷇
ⱪꞌ꞉ꜜ꞉ᴐԜꞌͼᴁᴟ꞉Ԝꞌͼ͟ᴟꜝᴡꜝᴐꜝꞌⱡͼⱫᴅ᷄᷉Ⱡ᷊᷊᷇᷄᷇
ⱨꜛᴒꜜᴑꜛᴒꜜᴡͼ᷊᷅᷇ͼⱴ꞉ꜜԜꞌⱡͼ᷇ⱠͼꜗԜꜜᴢԜᴟᴦ᷉᷇᷈ⅎ
ⱪꜝꜜⱱ꞉ᴑᴒꜜᴡ꞉Ԝꞌ
͟ԜⱲᴒͼⅎⅎ
ⱫᴦԜᴥͼⱪꜝᴟꜞ᷅
8
QUALITY CONTROL AND ASSURANCE
ᴁⱳᴒͼᴀꜞꜝꜜᴠꜝᴟͼԜꜜᴑͼᴡⱳᴒͼⱪꜝꜜᴡᴟԜᴐᴡͼϸᴒᴠᴒԜᴟᴐⱳͼ꜡ᴟⱲԜꜜ꞉ᴧԜᴡ꞉ꜝꜜͼӿⱪϸ꜡Ԑͼᴐꜝꜜᴑᴢᴐᴡ꞉ꜜⱲͼᴡᴟ꞉ԜꞌͼꜛԜꜜԜⱲᴒꜛᴒꜜᴡͼ
ᴠᴒᴟᴣ꞉ᴐᴒᴠԓͼϸⱳꜝԓͼⱷꜜᴐ᷅ͼᴤ꞉ꞌꞌͼ꞉ꜛꜞꞌᴒꜛᴒꜜᴡͼԜͼᴠᴦᴠᴡᴒꜛͼꜝⱱͼꜟᴢԜꞌ꞉ᴡᴦͼԜᴠᴠᴢᴟԜꜜᴐᴒͼᴡⱳԜᴡͼ꞉ꜜᴐꞌᴢᴑᴒᴠͼԜꞌꞌͼᴒꞌᴒꜛᴒꜜᴡᴠͼ
ᴑᴒᴠᴐᴟ꞉ԝᴒᴑͼ꞉ꜜͼᴡⱳ꞉ᴠͼꜞᴟꜝᴡꜝᴐꜝꞌ᷅ͼᴄ꞉ᴡⱳ꞉ꜜͼᴡⱳ꞉ᴠͼᴠᴦᴠᴡᴒꜛԓͼᴀ꜡͟ᴠͼⱱᴟꜝꜛͼᴡⱳᴒͼᴀꜞꜝꜜᴠꜝᴟͼԜꜜᴑͼⱪϸ꜡ͼᴤ꞉ꞌꞌͼԝᴒͼ
꞉ꜛꜞꞌᴒꜛᴒꜜᴡᴒᴑͼᴡꜝͼᴒꜜᴠᴢᴟᴒͼᴡⱳԜᴡͼᴡⱳᴒͼᴐꞌ꞉ꜜ꞉ᴐԜꞌͼᴡᴟ꞉Ԝꞌͼ꞉ᴠͼᴐꜝꜜᴑᴢᴐᴡᴒᴑͼ꞉ꜜͼᴐꜝꜛꜞꞌ꞉Ԝꜜᴐᴒͼᴤ꞉ᴡⱳͼᴟᴒⱲᴢꞌԜᴡꜝᴟᴦͼ
ᴟᴒꜟᴢ꞉ᴟᴒꜛᴒꜜᴡᴠͼԜꜜᴑͼⱵꜝꜝᴑͼⱪꞌ꞉ꜜ꞉ᴐԜꞌͼ͟ᴟԜᴐᴡ꞉ᴐᴒᴠͼӿⱵⱪ͟Ԑ᷅ͼϷᴢԜꞌ꞉ᴡᴦͼᴐꜝꜜᴡᴟꜝꞌͼᴤ꞉ꞌꞌͼԝᴒͼԜꜞꜞꞌ꞉ᴒᴑͼᴡꜝͼᴒԜᴐⱳͼᴠᴡԜⱲᴒͼꜝⱱͼ
ᴑԜᴡԜͼⱳԜꜜᴑꞌ꞉ꜜⱲͼᴡꜝͼᴒꜜᴠᴢᴟᴒͼᴡⱳԜᴡͼᴑԜᴡԜͼԜᴟᴒͼԜᴐᴐᴢᴟԜᴡᴒԓͼᴟᴒꞌ꞉ԜԝꞌᴒͼԜꜜᴑͼꜞᴟꜝᴐᴒᴠᴠᴒᴑͼᴐꜝᴟᴟᴒᴐᴡꞌᴦ᷅ͼ
ᴁⱳᴒͼᴠ꞉ᴡᴒͼᴠᴡԜⱱⱱͼᴠⱳꜝᴢꞌᴑͼԜᴠᴠ꞉ᴠᴡͼ꞉ꜜͼԜꞌꞌͼԜᴠꜞᴒᴐᴡᴠͼꜝⱱͼԜᴢᴑ꞉ᴡ᷆꞉ꜜᴠꜞᴒᴐᴡ꞉ꜝꜜ᷅

Ⱬᴅ᷄᷉Ⱡ᷊᷇
ⱪꞌ꞉ꜜ꞉ᴐԜꞌͼᴁᴟ꞉Ԝꞌͼ͟ᴟꜝᴡꜝᴐꜝꞌⱡͼⱫᴅ᷄᷉Ⱡ᷊᷊᷇᷄᷇
ⱨꜛᴒꜜᴑꜛᴒꜜᴡͼ᷊᷅᷇ͼⱴ꞉ꜜԜꞌⱡͼ᷇ⱠͼꜗԜꜜᴢԜᴟᴦ᷉᷇᷈ⅎ
ⱪꜝꜜⱱ꞉ᴑᴒꜜᴡ꞉Ԝꞌ
͟ԜⱲᴒͼⅎ˲
ⱫᴦԜᴥͼⱪꜝᴟꜞ᷅
9
DATA ANALYSIS / STATISTICAL METHODS
9.1
General Considerations
ⱨꞌꞌͼᴠᴡԜᴡ꞉ᴠᴡ꞉ᴐԜꞌͼԜꜜԜꞌᴦᴠᴒᴠͼᴤ꞉ꞌꞌͼԝᴒͼꜞᴒᴟⱱꜝᴟꜛᴒᴑͼᴢᴠ꞉ꜜⱲͼᴀⱨᴀᶇᴃᴒᴟᴠ꞉ꜝꜜͼⱠ᷊᷅ͼꜝᴟͼⱳ꞉Ⱳⱳᴒᴟͼӿᴀⱨᴀͼⱷꜜᴠᴡ꞉ᴡᴢᴡᴒԓͼ
ԓͼ
ԓͼᴂᴀⱨԐ᷅
ᴂꜜꞌᴒᴠᴠͼꜝᴡⱳᴒᴟᴤ꞉ᴠᴒͼᴠꜞᴒᴐ꞉ⱱ꞉ᴒᴑԓͼᴠᴢꜛꜛԜᴟᴦͼᴡԜԝᴢꞌԜᴡ꞉ꜝꜜᴠͼᴤ꞉ꞌꞌͼԝᴒͼꜞᴟᴒᴠᴒꜜᴡᴒᴑͼԝᴦͼᴡᴟᴒԜᴡꜛᴒꜜᴡͼⱲᴟꜝᴢꜞ᷅ͼⱴꜝᴟͼ
ᴐԜᴡᴒⱲꜝᴟ꞉ᴐԜꞌͼᴣԜᴟ꞉ԜԝꞌᴒᴠԓͼᴡⱳᴒͼꜜᴢꜛԝᴒᴟͼԜꜜᴑͼꜞᴒᴟᴐᴒꜜᴡԜⱲᴒͼꜝⱱͼᴠᴢԝ꞊ᴒᴐᴡᴠͼᴤ꞉ᴡⱳ꞉ꜜͼᴒԜᴐⱳͼᴐԜᴡᴒⱲꜝᴟᴦͼӿᴤ꞉ᴡⱳͼԜͼ
ᴐԜᴡᴒⱲꜝᴟᴦͼⱱꜝᴟͼꜛ꞉ᴠᴠ꞉ꜜⱲͼᴑԜᴡԜͼԜᴠͼꜜᴒᴒᴑᴒᴑԐͼꜝⱱͼᴡⱳᴒͼꜞԜᴟԜꜛᴒᴡᴒᴟͼᴤ꞉ꞌꞌͼԝᴒͼꜞᴟᴒᴠᴒꜜᴡᴒᴑ᷅ͼⱴꜝᴟͼᴐꜝꜜᴡ꞉ꜜᴢꜝᴢᴠͼ
ᴣԜᴟ꞉Ԝԝꞌᴒᴠԓͼᴡⱳᴒͼꜜᴢꜛԝᴒᴟͼꜝⱱͼᴠᴢԝ꞊ᴒᴐᴡᴠԓͼꜛᴒԜꜜԓͼꜛᴒᴑ꞉ԜꜜԓͼᴠᴡԜꜜᴑԜᴟᴑͼᴑᴒᴣ꞉Ԝᴡ꞉ꜝꜜͼӿᴀⱫԐԓͼꜛ꞉ꜜ꞉ꜛᴢꜛԓͼԜꜜᴑͼ
ꜛԜᴥ꞉ꜛᴢꜛͼᴣԜꞌᴢᴒᴠͼᴤ꞉ꞌꞌͼԝᴒͼꜞᴟᴒᴠᴒꜜᴡᴒᴑ᷅ͼᴄⱳᴒᴟᴒͼԜꜞꜞꞌ꞉ᴐԜԝꞌᴒԓͼᴒᴠᴡ꞉ꜛԜᴡᴒᴠͼⱱᴟꜝꜛͼᴠᴡԜᴡ꞉ᴠᴡ꞉ᴐԜꞌͼꜛꜝᴑᴒꞌͼꜝⱱͼꞌᴒԜᴠᴡͼ
ᴠꜟᴢԜᴟᴒᴠͼꜛᴒԜꜜᴠԓͼᴡᴟᴒԜᴡꜛᴒꜜᴡͼᴑ꞉ⱱⱱᴒᴟᴒꜜᴐᴒᴠԓͼꜞ᷄ᴣԜꞌᴢᴒᴠԓͼԜꜜᴑͼⱠ᷿Ӽͼᴐꜝꜜⱱ꞉ᴑᴒꜜᴐᴒͼ꞉ꜜᴡᴒᴟᴣԜꞌᴠͼⱱꜝᴟͼꞌᴒԜᴠᴡͼᴠꜟᴢԜᴟᴒᴠͼ
ꜛᴒԜꜜͼᴡᴟᴒԜᴡꜛᴒꜜᴡͼᴑ꞉ⱱⱱᴒᴟᴒꜜᴐᴒᴠͼᴤ꞉ꞌꞌͼԝᴒͼꜞᴟꜝᴣ꞉ᴑᴒᴑ᷅ͼᴁ꞉ꜛᴒ᷄ᴡꜝ᷄ᴒᴣᴒꜜᴡͼᴑԜᴡԜͼᴤ꞉ꞌꞌͼԝᴒͼᴠᴢꜛꜛԜᴟ꞉ᴧᴒᴑͼᴢᴠ꞉ꜜⱲͼ
ꜘԜꜞꞌԜꜜ᷄ꜚᴒ꞉ᴒᴟͼᴒᴠᴡ꞉ꜛԜᴡᴒᴠͼꜝⱱͼᴡⱳᴒͼ᷿᷉ᴡⱳԓͼ᷿᷇ᴡⱳͼӿꜛᴒᴑ꞉ԜꜜԐԓͼԜꜜᴑͼⅎ᷿ᴡⱳͼꜞᴒᴟᴐᴒꜜᴡ꞉ꞌᴒᴠͼᴤ꞉ᴡⱳͼԜᴠᴠꜝᴐ꞉Ԝᴡᴒᴑͼᴡᴤꜝ᷄
ᴠ꞉ᴑᴒᴑͼⱠ᷿Ӽͼᴐꜝꜜⱱ꞉ᴑᴒꜜᴐᴒͼ꞉ꜜᴡᴒᴟᴣԜꞌᴠԓͼԜᴠͼᴤᴒꞌꞌͼԜᴠͼꜞᴒᴟᴐᴒꜜᴡԜⱲᴒͼꜝⱱͼᴐᴒꜜᴠꜝᴟᴒᴑͼꜝԝᴠᴒᴟᴣԜᴡ꞉ꜝꜜᴠ᷅ͼ͟ꞌꜝᴡᴠͼꜝⱱͼᴡⱳᴒͼ
ꜘԜꜞꞌԜꜜ᷄ꜚᴒ꞉ᴒᴟͼᴐᴢᴟᴣᴒᴠͼԜꜜᴑͼᴠᴢꜞꜞꜝᴟᴡ꞉ꜜⱲͼᴑԜᴡԜͼꞌ꞉ᴠᴡ꞉ꜜⱲᴠͼᴑᴒᴡԜ꞉ꞌ꞉ꜜⱲͼᴒԜᴐⱳͼᴠᴢԝ꞊ᴒᴐᴡᶳᴠͼᴐꜝꜜᴡᴟ꞉ԝᴢᴡ꞉ꜝꜜͼᴡꜝͼᴡⱳᴒͼ
ԜꜜԜꞌᴦᴠ꞉ᴠͼᴤ꞉ꞌꞌͼԝᴒͼꜞᴟꜝᴣ꞉ᴑᴒᴑ᷅ͼ
ⱴꜝᴟꜛԜꞌͼᴠᴡԜᴡ꞉ᴠᴡ꞉ᴐԜꞌͼⱳᴦꜞꜝᴡⱳᴒᴠ꞉ᴠͼᴡᴒᴠᴡ꞉ꜜⱲͼᴤ꞉ꞌꞌͼԝᴒͼꜞᴒᴟⱱꜝᴟꜛᴒᴑͼꜝꜜͼᴡⱳᴒͼꜞᴟ꞉ꜛԜᴟᴦͼԜꜜᴑͼᴟԜꜜꞋͼꜝᴟᴑᴒᴟᴒᴑͼ
ᴠᴒᴐꜝꜜᴑԜᴟᴦͼᴒⱱⱱ꞉ᴐԜᴐᴦͼᴒꜜᴑꜞꜝ꞉ꜜᴡᴠͼᴤ꞉ᴡⱳͼᴡⱳᴒͼⱲꞌꜝԝԜꞌͼⱱԜꜛ꞉ꞌᴦ᷄ᴤ꞉ᴠᴒͼᴡᴦꜞᴒͼⱷͼᴒᴟᴟꜝᴟͼᴟԜᴡᴒͼӿⱴᴄⱬϸԐͼᴠᴡᴟꜝꜜⱲꞌᴦͼ
ᴐꜝꜜᴡᴟꜝꞌꞌᴒᴑͼԜᴡͼᴡᴤꜝ᷄ᴠ꞉ᴑᴒᴑͼ᷿᷇᷅᷇ͼᴢᴠ꞉ꜜⱲͼԜͼⱩꜝꜜⱱᴒᴟᴟꜝꜜ꞉᷄ԝԜᴠᴒᴑͼⱲᴒꜜᴒᴟԜꞌͼⱲԜᴡᴒꞋᴒᴒꜞ꞉ꜜⱲͼꜞᴟꜝᴐᴒᴑᴢᴟᴒͼԜᴠͼ
ᴑᴒᴠᴐᴟ꞉ԝᴒᴑͼ꞉ꜜͼᴀᴒᴐᴡ꞉ꜝꜜͼⱠ᷿᷅᷈᷉᷅᷅ͼ
9.2
Sample Size Determination
͟ꜝᴤᴒᴟͼԜꜜԜꞌᴦᴠ꞉ᴠͼԜꜜᴑͼᴠԜꜛꜞꞌᴒͼᴠ꞉ᴧᴒͼᴒᴠᴡ꞉ꜛԜᴡ꞉ꜝꜜͼᴤԜᴠͼԝԜᴠᴒᴑͼꜝꜜͼ᷈᷇᷇᷇ͼᴐꜝꜛꜞᴢᴡᴒᴟͼᴠ꞉ꜛᴢꞌԜᴡ꞉ꜝꜜᴠͼᴢᴠ꞉ꜜⱲͼԜͼ
ⱲᴒꜜᴒᴟԜꞌ꞉ᴧᴒᴑͼꞌ꞉ꜜᴒԜᴟͼꜛꜝᴑᴒꞌͼⱱꜝᴟͼᴐꜝᴢꜜᴡͼᴑԜᴡԜͼԜᴠᴠᴢꜛ꞉ꜜⱲͼԜͼ͟ꜝ꞉ᴠᴠꜝꜜͼᴑ꞉ᴠᴡᴟ꞉ԝᴢᴡ꞉ꜝꜜͼᴤ꞉ᴡⱳͼ͟ᴒԜᴟᴠꜝꜜͼᴐⱳ꞉᷄ᴠꜟᴢԜᴟᴒͼ
ᴠᴐԜꞌ꞉ꜜⱲͼꜝⱱͼᴠᴡԜꜜᴑԜᴟᴑͼᴒᴟᴟꜝᴟᴠͼᴡꜝͼԜᴐᴐꜝᴢꜜᴡͼⱱꜝᴟͼꜞꜝᴡᴒꜜᴡ꞉Ԝꞌͼꜝᴣᴒᴟᴑ꞉ᴠꜞᴒᴟᴠ꞉ꜝꜜ᷅ͼᴁⱳᴒͼԜᴐᴡ꞉ᴣᴒͼᴡᴟᴒԜᴡꜛᴒꜜᴡͼᴑꜝᴠᴒͼ꞉ꜜͼ
ᴒԜᴐⱳͼԜᴐᴡ꞉ᴣᴒͼᴡᴟᴒԜᴡꜛᴒꜜᴡͼԜᴟꜛͼᴡꜝͼꜞꞌԜᴐᴒԝꜝͼᴟԜᴡ꞉ꜝͼᴤԜᴠͼᴠᴒᴡͼԜᴡͼ᷈ⱡ᷿᷈᷅᷅ͼⱨͼ᷈᷇Ӽͼꜛ꞉ᴠᴠ꞉ꜜⱲͼᴑԜᴡԜ᷆ᴑᴟꜝꜞꜝᴢᴡͼᴟԜᴡᴒͼⱱꜝᴟͼ
ԝꜝᴡⱳͼԜᴐᴡ꞉ᴣᴒͼᴡᴟᴒԜᴡꜛᴒꜜᴡͼԜꜜᴑͼꜞꞌԜᴐᴒԝꜝͼᴤԜᴠͼԜꞌᴠꜝͼԝᴢ꞉ꞌᴡͼ꞉ꜜᴡꜝͼᴡⱳᴒͼᴒꜛꜞ꞉ᴟ꞉ᴐԜꞌͼᴠԜꜛꜞꞌᴒͼᴠ꞉ᴧᴒͼᴠ꞉ꜛᴢꞌԜᴡ꞉ꜝꜜᴠ᷅
ⱴꜝᴟͼԜͼᴡᴟᴒԜᴡꜛᴒꜜᴡͼᴒⱱⱱᴒᴐᴡͼꜝⱱͼ⅍᷇Ӽͼᴟᴒᴑᴢᴐᴡ꞉ꜝꜜͼ꞉ꜜͼԜᴡᴡԜᴐꞋᴠͼԜᴠͼᴐꜝꜛꜞԜᴟᴒᴑͼᴡꜝͼꜞꞌԜᴐᴒԝꜝԓͼԜᴠᴠᴢꜛ꞉ꜜⱲͼԜͼꜞꞌԜᴐᴒԝꜝͼ
ԜᴡᴡԜᴐꞋͼᴟԜᴡᴒͼꜝⱱͼ᷊᷇᷅ͼԜᴡᴡԜᴐꞋᴠͼꜞᴒᴟͼᴤᴒᴒꞋͼꜝᴣᴒᴟͼԜͼ᷉⅍ͼᴤᴒᴒꞋͼꜞᴒᴟ꞉ꜝᴑͼⱱꜝᴟͼԜꜜͼԜᴣᴒᴟԜⱲᴒͼᴡꜝᴡԜꞌͼꜝⱱͼⅎ᷅˲ͼԜᴡᴡԜᴐꞋᴠͼ
ᴑᴢᴟ꞉ꜜⱲͼᴡⱳᴒᴡᴟᴒԜᴡꜛᴒꜜᴡͼꜞᴒᴟ꞉ꜝᴑԓͼԜͼᴠԜꜛꜞꞌᴒͼᴠ꞉ᴧᴒͼꜝⱱͼ᷉᷾ͼԜᴐᴡ꞉ᴣᴒꞌᴦͼᴡᴟᴒԜᴡᴒᴑͼᴠᴢԝ꞊ᴒᴐᴡᴠͼⱱꜝᴟͼᴡⱳᴒͼꜞᴟ꞉ꜛԜᴟᴦͼԜᴐᴡ꞉ᴣᴒͼ
ᴡᴟᴒԜᴡꜛᴒꜜᴡͼԜᴟꜛͼԜꜜᴑͼ᷊⅍ͼꜞꞌԜᴐᴒԝꜝͼᴠᴢԝ꞊ᴒᴐᴡᴠͼᴤꜝᴢꞌᴑͼꜞᴟꜝᴣ꞉ᴑᴒͼԜᴡͼꞌᴒԜᴠᴡͼⱠ᷿ӼͼꜞꜝᴤᴒᴟͼӿԜᴡͼԜꞌꜞⱳԜⱤ᷿᷇᷅᷇᷉ԓͼ
ꜝꜜᴒ᷄ᴠ꞉ᴑᴒᴑԐ᷅ͼⱨͼ⅍᷇Ӽͼᴟᴒᴑᴢᴐᴡ꞉ꜝꜜͼ꞉ᴠͼᴤᴒꞌꞌͼԝᴒꞌꜝᴤͼᴡⱳᴒͼᴠꜛԜꞌꞌᴒᴠᴡͼᴒᴥꜞᴒᴐᴡᴒᴑͼᴟᴒᴑᴢᴐᴡ꞉ꜝꜜͼ꞉ꜜͼԜᴡᴡԜᴐꞋᴠԓͼⱱꜝᴟͼ꞉ꜜͼᴡⱳᴒͼ
Ⱬᴅ᷄᷉Ⱡ᷊᷇᷄᷇᷉ͼᴠᴡᴢᴑᴦԓͼᴤᴒͼꜝԝᴠᴒᴟᴣᴒᴑͼᴟᴒᴑᴢᴐᴡ꞉ꜝꜜᴠͼꜝⱱͼԜᴡᴡԜᴐꞋᴠͼꜝⱱͼꜜᴒԜᴟͼ᷈᷇᷇Ӽ᷅ͼᴁⱳᴒᴠᴒͼᴠԜꜛꜞꞌᴒͼᴠ꞉ᴧᴒᴠͼᴤ꞉ꞌꞌͼ
Ԝꞌᴠꜝͼꜞᴟꜝᴣ꞉ᴑᴒͼԜᴑᴒꜟᴢԜᴡᴒꞌᴦͼᴠ꞉ᴧᴒᴑͼᴠԜⱱᴒᴡᴦͼꜞꜝꜞᴢꞌԜᴡ꞉ꜝꜜͼⱱꜝᴟͼᴒᴣԜꞌᴢԜᴡ꞉ꜝꜜ᷅ͼᴂꜞͼᴡꜝͼ᷈᷉᷇ᴠᴢԝ꞊ᴒᴐᴡᴠͼ
ӿԜꜞꜞᴟꜝᴥ꞉ꜛԜᴡᴒꞌᴦͼ˲᷇ͼᴠᴢԝ꞊ᴒᴐᴡᴠͼ꞉ꜜͼᴡⱳᴒͼ᷊ͼԜᴐᴡ꞉ᴣᴒͼᴡᴟᴒԜᴡꜛᴒꜜᴡͼⱲᴟꜝᴢꜞᴠͼԜꜜᴑͼ᷾᷇꞉ꜜͼᴡⱳᴒͼꜞꞌԜᴐᴒԝꜝͼⱲᴟꜝᴢꜞԐͼꜛԜᴦͼԝᴒͼ
ᴒꜜᴟꜝꞌꞌᴒᴑͼᴡꜝͼԜᴐᴐꜝᴢꜜᴡͼⱱꜝᴟͼꜞꜝᴡᴒꜜᴡ꞉ԜꞌͼᴒԜᴟꞌᴦͼᴑᴟꜝꜞꜝᴢᴡᴠͼᴑᴢᴟ꞉ꜜⱲͼᴡⱳᴒͼᴠᴡᴢᴑᴦ᷅
9.3
Method of Assigning Study Subjects to Treatment Groups
ᴀᴢԝ꞊ᴒᴐᴡᴠͼᴤ꞉ꞌꞌͼԝᴒͼᴟԜꜜᴑꜝꜛ꞉ᴧᴒᴑͼԜⱱᴡᴒᴟͼᴐꜝꜜⱱ꞉ᴟꜛԜᴡ꞉ꜝꜜͼꜝⱱͼᴠᴡᴢᴑᴦͼᴒꞌ꞉Ⱳ꞉ԝ꞉ꞌ꞉ᴡᴦͼ꞉ꜜͼԜͼᴟԜᴡ꞉ꜝͼꜝⱱͼ᷉ⱡ᷈ͼᴣ꞉ԜͼԜͼ
ᴐꜝꜛꜞᴢᴡᴒᴟ᷄ⱲᴒꜜᴒᴟԜᴡᴒᴑͼᴟԜꜜᴑꜝꜛ꞉ᴧԜᴡ꞉ꜝꜜͼᴠᴐⱳᴒᴑᴢꞌᴒͼᴡꜝͼᴟᴒᴐᴒ꞉ᴣᴒͼᴟᴒꜞᴒԜᴡᴒᴑͼᴀⱪͼԜᴑꜛ꞉ꜜ꞉ᴠᴡᴟԜᴡ꞉ꜝꜜᴠͼꜝⱱͼⱫᴅ᷄᷉Ⱡ᷊᷇ͼ
PPD
PPD

Ⱬᴅ᷄᷉Ⱡ᷊᷇
ⱪꞌ꞉ꜜ꞉ᴐԜꞌͼᴁᴟ꞉Ԝꞌͼ͟ᴟꜝᴡꜝᴐꜝꞌⱡͼⱫᴅ᷄᷉Ⱡ᷊᷊᷇᷄᷇
ⱨꜛᴒꜜᴑꜛᴒꜜᴡͼ᷊᷅᷇ͼⱴ꞉ꜜԜꞌⱡͼ᷇ⱠͼꜗԜꜜᴢԜᴟᴦ᷉᷇᷈ⅎ
ⱪꜝꜜⱱ꞉ᴑᴒꜜᴡ꞉Ԝꞌ
͟ԜⱲᴒͼⅎⱠ
ⱫᴦԜᴥͼⱪꜝᴟꜞ᷅
ꜝᴟͼꜞꞌԜᴐᴒԝꜝ᷅ͼᴀᴢԝ꞊ᴒᴐᴡᴠͼᴤⱳꜝͼԜᴟᴒͼᴟԜꜜᴑꜝꜛ꞉ᴧᴒᴑͼᴡꜝͼⱫᴅ᷄᷉Ⱡ᷊᷇ͼᴤ꞉ꞌꞌͼԝᴒͼԜᴠᴠ꞉Ⱳꜜᴒᴑͼ꞉ꜜͼԜͼ᷈ⱡ᷈ⱡ᷈ᴟԜᴡ꞉ꜝͼᴡꜝͼ᷈ͼꜝⱱͼ᷊ͼ
ᴑꜝᴠ꞉ꜜⱲͼᴟᴒⱲ꞉ꜛᴒꜜᴠⱡͼ᷊᷇᷇ͼꜛⱲͼᴒᴣᴒᴟᴦͼ᷉ͼᴤᴒᴒꞋᴠԓͼ᷊᷇᷇ͼꜛⱲͼᴒᴣᴒᴟᴦͼ᷾ͼᴤᴒᴒꞋᴠԓͼꜝᴟͼ᷿᷈᷇ꜛⱲͼᴒᴣᴒᴟᴦͼ᷾ͼᴤᴒᴒꞋᴠ᷅ͼ
ϸԜꜜᴑꜝꜛ꞉ᴧԜᴡ꞉ꜝꜜͼᴤ꞉ꞌꞌͼԝᴒͼꜞᴒᴟⱱꜝᴟꜛᴒᴑͼᴐᴒꜜᴡᴟԜꞌꞌᴦͼԜꜜᴑͼᴠᴡᴟԜᴡ꞉ⱱ꞉ᴒᴑͼԝᴦͼᴡⱳᴒͼԝԜᴠᴒꞌ꞉ꜜᴒͼԜᴡᴡԜᴐꞋͼᴟԜᴡᴒͼꜝԝᴠᴒᴟᴣᴒᴑͼ
ᴑᴢᴟ꞉ꜜⱲͼᴡⱳᴒͼᴟᴢꜜ᷄꞉ꜜͼꜞᴒᴟ꞉ꜝᴑͼ꞉ꜜᴡꜝͼᴡⱳᴒͼⱱꜝꞌꞌꜝᴤ꞉ꜜⱲͼⱲᴟꜝᴢꜞᴠⱡͼ᷈ͼᴡꜝͼⱣͼ᷉ͼԜᴡᴡԜᴐꞋᴠͼꜞᴒᴟͼ᷾ͼᴤᴒᴒꞋᴠԓͼ᷉ͼᴡꜝͼⱣͼ᷊ͼԜᴡᴡԜᴐꞋᴠͼ
ꜞᴒᴟͼ᷾ͼᴤᴒᴒꞋᴠԓͼԜꜜᴑͼᶒͼ᷊ͼԜᴡᴡԜᴐꞋᴠͼꜞᴒᴟͼ᷾ͼᴤᴒᴒꞋᴠ᷅ͼ͟ᴒᴟꜛᴢᴡᴒᴑͼԝꞌꜝᴐꞋᴠͼᴤ꞉ꞌꞌͼԝᴒͼᴢᴠᴒᴑͼᴡꜝͼᴒꜜᴠᴢᴟᴒͼᴡⱳԜᴡͼ
Ԝꜞꜞᴟꜝᴥ꞉ꜛԜᴡᴒꞌᴦͼᴒꜟᴢԜꞌͼꜜᴢꜛԝᴒᴟᴠͼꜝⱱͼᴠᴢԝ꞊ᴒᴐᴡᴠͼԜᴟᴒͼԜᴠᴠ꞉ⱲꜜᴒᴑͼᴒԜᴐⱳͼᴡᴟᴒԜᴡꜛᴒꜜᴡͼᴤ꞉ᴡⱳ꞉ꜜͼᴠᴡᴟԜᴡԜ᷅
9.4
Analysis Populations
ᴁⱳᴒͼԜꜜԜꞌᴦᴠ꞉ᴠͼꜞꜝꜞᴢꞌԜᴡ꞉ꜝꜜᴠͼᴤ꞉ꞌꞌͼԝᴒͼᴑᴒⱱ꞉ꜜᴒᴑͼԜᴠͼⱱꜝꞌꞌꜝᴤᴠⱡͼ
Intent-to-treat (ITT) Population: ᴤ꞉ꞌꞌͼ꞉ꜜᴐꞌᴢᴑᴒͼԜꞌꞌͼᴟԜꜜᴑꜝꜛ꞉ᴧᴒᴑͼᴠᴢԝ꞊ᴒᴐᴡᴠᴤⱳꜝͼԜᴟᴒͼԜᴑꜛ꞉ꜜ꞉ᴠᴡᴒᴟᴒᴑͼԜᴡͼ
ꞌᴒԜᴠᴡͼ᷈ͼᴑꜝᴠᴒͼꜝⱱͼԜᴐᴡ꞉ᴣᴒͼⱷꜚ͟ͼꜝᴟͼꜞꞌԜᴐᴒԝꜝ᷅ͼᴀᴢԝ꞊ᴒᴐᴡᴠͼᴤ꞉ꞌꞌͼԝᴒͼԜꜜԜꞌᴦᴧᴒᴑͼԜᴐᴐꜝᴟᴑ꞉ꜜⱲͼᴡꜝͼᴡⱳᴒ꞉ᴟͼᴟԜꜜᴑꜝꜛ꞉ᴧᴒᴑͼ
ᴡᴟᴒԜᴡꜛᴒꜜᴡͼԜᴠᴠ꞉ⱲꜜꜛᴒꜜᴡͼᴟᴒⱲԜᴟᴑꞌᴒᴠᴠͼꜝⱱͼᴡⱳᴒͼᴡᴟᴒԜᴡꜛᴒꜜᴡͼԜᴐᴡᴢԜꞌꞌᴦͼᴟᴒᴐᴒ꞉ᴣᴒᴑ᷅ͼᴁⱳᴒͼꜞᴟ꞉ꜛԜᴟᴦͼᴒⱱⱱ꞉ᴐԜᴐᴦͼ
ԜꜜԜꞌᴦᴠᴒᴠͼᴤ꞉ꞌꞌͼԝᴒͼᴐԜᴟᴟ꞉ᴒᴑͼꜝᴢᴡͼᴤ꞉ᴡⱳͼᴡⱳᴒͼⱷᴁᴁͼ͟ꜝꜞᴢꞌԜᴡ꞉ꜝꜜ᷅
Safety Population: ᴤ꞉ꞌꞌͼ꞉ꜜᴐꞌᴢᴑᴒͼԜꞌꞌͼᴠᴢԝ꞊ᴒᴐᴡᴠͼᴤⱳꜝͼԜᴟᴒͼԜᴑꜛ꞉ꜜ꞉ᴠᴡᴒᴟᴒᴑͼԜᴡͼꞌᴒԜᴠᴡͼ᷈ͼᴑꜝᴠᴒͼꜝⱱͼԜᴐᴡ꞉ᴣᴒͼⱷꜚ͟ͼ
ꜝᴟͼꜞꞌԜᴐᴒԝꜝ᷅ͼᴀᴢԝ꞊ᴒᴐᴡᴠͼᴤ꞉ꞌꞌͼԝᴒͼԜꜜԜꞌᴦᴧᴒᴑͼԜᴐᴐꜝᴟᴑ꞉ꜜⱲͼᴡꜝͼᴡⱳᴒͼᴡᴟᴒԜᴡꜛᴒꜜᴡͼᴡⱳᴒᴦͼԜᴐᴡᴢԜꞌꞌᴦͼᴟᴒᴐᴒ꞉ᴣᴒᴑ᷅ͼⱨꞌꞌ
ᴠԜⱱᴒᴡᴦԜꜜԜꞌᴦᴠᴒᴠᴤ꞉ꞌꞌᴢᴠᴒᴡⱳᴒᴀԜⱱᴒᴡᴦ͟ꜝꜞᴢꞌԜᴡ꞉ꜝꜜ᷅
9.5
Analysis of Disposition
ᴁⱳᴒͼꜜᴢꜛԝᴒᴟᴠͼꜝⱱͼᴠᴢԝ꞊ᴒᴐᴡᴠͼᴟԜꜜᴑꜝꜛ꞉ᴧᴒᴑԓͼᴐꜝꜛꜞꞌᴒᴡ꞉ꜜⱲԓͼꜝᴟͼᴤ꞉ᴡⱳᴑᴟԜᴤ꞉ꜜⱲԓͼԜꞌꜝꜜⱲͼᴤ꞉ᴡⱳͼᴟᴒԜᴠꜝꜜᴠͼⱱꜝᴟͼ
ᴤ꞉ᴡⱳᴑᴟԜᴤԜꞌԓͼᴤ꞉ꞌꞌͼԝᴒͼᴡԜԝᴢꞌԜᴡᴒᴑͼԝᴦͼᴡᴟᴒԜᴡꜛᴒꜜᴡͼⱲᴟꜝᴢꜞͼԜꜜᴑͼꜝᴣᴒᴟԜꞌꞌͼⱱꜝᴟͼᴡⱳᴒͼⱷᴁᴁͼԜꜜᴑͼᴠԜⱱᴒᴡᴦͼꜞꜝꜞᴢꞌԜᴡ꞉ꜝꜜᴠ᷅
9.6
Demographics and Baseline Characteristics Analyses
ⱩԜᴠᴒꞌ꞉ꜜᴒͼԜꜜᴑͼᴑᴒꜛꜝⱲᴟԜꜞⱳ꞉ᴐͼᴣԜᴟ꞉Ԝԝꞌᴒᴠͼᴤ꞉ꞌꞌͼԝᴒͼᴑᴒᴠᴐᴟ꞉ꜞᴡ꞉ᴣᴒꞌᴦͼᴠᴢꜛꜛԜᴟ꞉ᴧᴒᴑͼԝᴦͼᴡᴟᴒԜᴡꜛᴒꜜᴡͼⱲᴟꜝᴢꜞͼԜꜜᴑͼ
ꜝᴣᴒᴟԜꞌꞌͼⱱꜝᴟͼᴡⱳᴒͼⱷᴁᴁͼԜꜜᴑͼᴠԜⱱᴒᴡᴦͼꜞꜝꜞᴢꞌԜᴡ꞉ꜝꜜᴠ᷅
9.7
Treatment Compliance and Extent of Exposure
ᴁᴟᴒԜᴡꜛᴒꜜᴡͼᴐꜝꜛꜞꞌ꞉ԜꜜᴐᴒͼԜꜜᴑͼᴒᴥᴡᴒꜜᴡͼꜝⱱͼᴒᴥꜞꜝᴠᴢᴟᴒͼᴤ꞉ꞌꞌͼԝᴒͼᴑᴒᴠᴐᴟ꞉ԝᴒᴑͼԝᴦͼᴐԜꞌᴐᴢꞌԜᴡ꞉ꜜⱲͼᴡⱳᴒͼꜞᴒᴟᴐᴒꜜᴡԜⱲᴒͼꜝⱱͼ
ꜞꞌԜꜜꜜᴒᴑͼᴑꜝᴠᴒᴠͼᴟᴒᴐᴒ꞉ᴣᴒᴑͼԝᴦͼᴡⱳᴒͼᴠᴢԝ꞊ᴒᴐᴡͼԜꜜᴑͼᴡⱳᴒͼᴡꜝᴡԜꞌͼꜜᴢꜛԝᴒᴟͼꜝⱱͼᴑꜝᴠᴒᴠͼᴟᴒᴐᴒ꞉ᴣᴒᴑͼԝᴦͼᴡⱳᴒͼᴠᴢԝ꞊ᴒᴐᴡͼԜꜜᴑͼ
ᴠᴢꜛꜛԜᴟ꞉ᴧᴒᴑͼԝᴦͼᴡᴟᴒԜᴡꜛᴒꜜᴡͼⱲᴟꜝᴢꜞͼⱱꜝᴟͼᴡⱳᴒͼⱷᴁᴁͼԜꜜᴑͼᴠԜⱱᴒᴡᴦͼꜞꜝꜞᴢꞌԜᴡ꞉ꜝꜜᴠ᷅
9.8
Analysis of Primary and Secondary Efficacy Endpoints
9.8.1 Primary Efficacy Endpoint
ᴁⱳᴒͼꜞᴟ꞉ꜛԜᴟᴦͼᴒⱱⱱ꞉ᴐԜᴐᴦͼᴒꜜᴑꜞꜝ꞉ꜜᴡԓͼꜜᴢꜛԝᴒᴟͼꜝⱱͼⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟ᷄ᴐꜝꜜⱱ꞉ᴟꜛᴒᴑͼⱶⱨⱬͼԜᴡᴡԜᴐꞋᴠͼᴑᴢᴟ꞉ꜜⱲͼᴡⱳᴒͼ
ᴒⱱⱱ꞉ᴐԜᴐᴦͼᴒᴣԜꞌᴢԜᴡ꞉ꜝꜜͼꜞᴒᴟ꞉ꜝᴑͼӿⱫԜᴦͼ᷇ͼᴡⱳᴟꜝᴢⱲⱳͼⱫԜᴦͼ᷈˲᷉Ԑԓͼᴤ꞉ꞌꞌͼԝᴒͼᴐꜝꜛꜞԜᴟᴒᴑͼⱱꜝᴟͼᴒԜᴐⱳͼԜᴐᴡ꞉ᴣᴒͼᴡᴟᴒԜᴡꜛᴒꜜᴡͼ
ⱲᴟꜝᴢꜞͼӿⱫᴅ᷄᷉Ⱡ᷊᷇ԐͼᴡꜝͼᴡⱳᴒͼꜞꞌԜᴐᴒԝꜝͼⱲᴟꜝᴢꜞͼᴢᴠ꞉ꜜⱲͼԜͼⱲᴒꜜᴒᴟԜꞌ꞉ᴧᴒᴑͼꞌ꞉ꜜᴒԜᴟͼꜛꜝᴑᴒꞌͼⱱꜝᴟͼᴐꜝᴢꜜᴡͼᴑԜᴡԜͼԜᴠᴠᴢꜛ꞉ꜜⱲͼ
Ԝͼ͟ꜝ꞉ᴠᴠꜝꜜͼᴑ꞉ᴠᴡᴟ꞉ԝᴢᴡ꞉ꜝꜜͼᴤ꞉ᴡⱳͼԜͼꞌꜝⱲͼꞌ꞉ꜜꞋͼⱱᴢꜜᴐᴡ꞉ꜝꜜͼԜꜜᴑͼ͟ᴒԜᴟᴠꜝꜜͼᴐⱳ꞉᷄ᴠꜟᴢԜᴟᴒͼᴠᴐԜꞌ꞉ꜜⱲͼꜝⱱͼᴠᴡԜꜜᴑԜᴟᴑͼᴒᴟᴟꜝᴟᴠͼ
ᴡꜝͼԜᴐᴐꜝᴢꜜᴡͼⱱꜝᴟͼꜞꜝᴡᴒꜜᴡ꞉Ԝꞌͼꜝᴣᴒᴟᴑ꞉ᴠꜞᴒᴟᴠ꞉ꜝꜜ᷅ͼᴁⱳᴒͼꜛꜝᴑᴒꞌͼᴤ꞉ꞌꞌͼ꞉ꜜᴐꞌᴢᴑᴒͼⱱ꞉ᴥᴒᴑͼᴒⱱⱱᴒᴐᴡᴠͼⱱꜝᴟͼᴡᴟᴒԜᴡꜛᴒꜜᴡͼⱲᴟꜝᴢꜞͼ
ӿᴐԜᴡᴒⱲꜝᴟ꞉ᴐԜꞌԐͼԜꜜᴑͼᴡⱳᴒͼꜜꜝᴟꜛԜꞌ꞉ᴧᴒᴑͼԝԜᴠᴒꞌ꞉ꜜᴒͼԜᴡᴡԜᴐꞋͼᴟԜᴡᴒͼӿᴐꜝꜜᴡ꞉ꜜᴢꜝᴢᴠԐԓͼԜꜜᴑͼᴡⱳᴒͼꞌꜝⱲԜᴟ꞉ᴡⱳꜛͼꜝⱱͼᴡ꞉ꜛᴒͼ꞉ꜜͼ

Ⱬᴅ᷄᷉Ⱡ᷊᷇
ⱪꞌ꞉ꜜ꞉ᴐԜꞌͼᴁᴟ꞉Ԝꞌͼ͟ᴟꜝᴡꜝᴐꜝꞌⱡͼⱫᴅ᷄᷉Ⱡ᷊᷊᷇᷄᷇
ⱨꜛᴒꜜᴑꜛᴒꜜᴡͼ᷊᷅᷇ͼⱴ꞉ꜜԜꞌⱡͼ᷇ⱠͼꜗԜꜜᴢԜᴟᴦ᷉᷇᷈ⅎ
ⱪꜝꜜⱱ꞉ᴑᴒꜜᴡ꞉Ԝꞌ
͟ԜⱲᴒͼ˲᷇
ⱫᴦԜᴥͼⱪꜝᴟꜞ᷅
ᴑԜᴦᴠͼᴒԜᴐⱳͼᴠᴢԝ꞊ᴒᴐᴡͼᴤԜᴠͼꜝԝᴠᴒᴟᴣᴒᴑͼᴑᴢᴟ꞉ꜜⱲͼᴡⱳᴒͼᴒⱱⱱ꞉ᴐԜᴐᴦͼᴒᴣԜꞌᴢԜᴡ꞉ꜝꜜͼꜞᴒᴟ꞉ꜝᴑͼᴤ꞉ꞌꞌͼԝᴒͼᴢᴠᴒᴑͼԜᴠͼԜꜜͼꜝⱱⱱᴠᴒᴡͼ
ᴣԜᴟ꞉Ԝԝꞌᴒͼ꞉ꜜͼᴡⱳᴒͼꜛꜝᴑᴒꞌ᷅ͼ
ⱴᴟꜝꜛͼᴡⱳ꞉ᴠͼꜛꜝᴑᴒꞌԓͼᴡⱳᴒͼꞌᴒԜᴠᴡͼᴠꜟᴢԜᴟᴒᴠͼꜛᴒԜꜜͼᴟԜᴡᴒͼԜꜜᴑͼᴠᴡԜꜜᴑԜᴟᴑͼᴒᴟᴟꜝᴟͼⱱꜝᴟͼᴒԜᴐⱳͼᴡᴟᴒԜᴡꜛᴒꜜᴡͼⱲᴟꜝᴢꜞͼԜᴠͼᴤᴒꞌꞌͼ
ԜᴠԓͼᴡⱳᴒͼꜛᴒԜꜜͼᴟԜᴡᴒͼᴟԜᴡ꞉ꜝᴠͼᴟᴒꞌԜᴡ꞉ᴣᴒͼᴡꜝͼᴡⱳᴒͼꜞꞌԜᴐᴒԝꜝͼⱲᴟꜝᴢꜞͼԜꜜᴑͼᴐꜝᴟᴟᴒᴠꜞꜝꜜᴑ꞉ꜜⱲͼⱠ᷿Ӽͼᴐꜝꜜⱱ꞉ᴑᴒꜜᴐᴒͼ꞉ꜜᴡᴒᴟᴣԜꞌᴠͼ
ⱱꜝᴟͼᴒԜᴐⱳͼԜᴐᴡ꞉ᴣᴒͼᴡᴟᴒԜᴡꜛᴒꜜᴡͼⱲᴟꜝᴢꜞͼᴤ꞉ꞌꞌͼԝᴒͼᴒᴠᴡ꞉ꜛԜᴡᴒᴑ᷅ͼᴁⱳᴒᴠᴒͼᴒᴠᴡ꞉ꜛԜᴡᴒᴠͼᴤ꞉ꞌꞌͼԝᴒͼᴟᴒꜞꜝᴟᴡᴒᴑͼԜᴠͼꜛᴒԜꜜͼᴒᴣᴒꜜᴡͼ
ᴟԜᴡᴒᴠͼꜞᴒᴟͼᴢꜜ꞉ᴡͼꜝⱱͼᴡ꞉ꜛᴒͼӿᴤᴒᴒꞋͼԜꜜᴑͼꜛꜝꜜᴡⱳꞌᴦԐͼԝᴦͼᴡᴟԜꜜᴠⱱꜝᴟꜛ꞉ꜜⱲͼᴡⱳᴒͼᴒᴠᴡ꞉ꜛԜᴡᴒᴠͼᴢᴠ꞉ꜜⱲͼᴡⱳᴒͼᴒᴥꜞꜝꜜᴒꜜᴡ꞉Ԝꞌͼ
ⱱᴢꜜᴐᴡ꞉ꜝꜜͼԜꜜᴑͼᴠᴐԜꞌ꞉ꜜⱲͼԝᴦͼᴡⱳᴒͼᴢꜜ꞉ᴡͼꜝⱱͼᴡ꞉ꜛᴒ᷅ͼ
ᴁⱳᴒͼꜞᴟ꞉ꜛԜᴟᴦͼᴒꜜᴑꜞꜝ꞉ꜜᴡͼᴤ꞉ꞌꞌͼԝᴒͼᴡᴒᴠᴡᴒᴑͼԝᴦͼᴡⱳᴒͼⱱꜝꞌꞌꜝᴤ꞉ꜜⱲͼⱳᴦꜞꜝᴡⱳᴒᴠ꞉ᴠⱡ
ⱶ᷇ⱡͼȜⱫᴅ᷄᷉Ⱡ᷊᷇᷆ͼȜꜞꞌԜᴐᴒԝꜝⱤͼ᷈ͼᴣᴒᴟᴠᴢᴠͼⱶ᷈ⱡͼȜⱫᴅ᷄᷉Ⱡ᷊᷇᷆ͼȜꜞꞌԜᴐᴒԝꜝᶌͼ᷈
ȜⱫᴅ᷄᷉Ⱡ᷊᷇ᴟᴒⱱᴒᴟᴠͼᴡꜝͼᴡⱳᴒͼꜛᴒԜꜜͼⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟ᷄ᴐꜝꜜⱱ꞉ᴟꜛᴒᴑͼⱶⱨⱬͼԜᴡᴡԜᴐꞋͼᴟԜᴡᴒͼ꞉ꜜͼᴡⱳᴒͼⱫᴅ᷄᷉Ⱡ᷊᷇ͼⱲᴟꜝᴢꜞͼԜꜜᴑͼ
ȜꜞꞌԜᴐᴒԝꜝͼᴟᴒⱱᴒᴟᴠͼᴡꜝͼᴡⱳᴒͼꜛᴒԜꜜͼⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟ᷄ᴐꜝꜜⱱ꞉ᴟꜛᴒᴑͼⱶⱨⱬͼԜᴡᴡԜᴐꞋͼᴟԜᴡᴒͼ꞉ꜜͼᴡⱳᴒͼꜞꞌԜᴐᴒԝꜝͼⱲᴟꜝᴢꜞ᷅ͼᴁⱳᴒͼꜜᴢꞌꞌͼ
ⱳᴦꜞꜝᴡⱳᴒᴠ꞉ᴠͼ꞉ᴠͼᴡⱳԜᴡͼᴡⱳᴒͼꜛᴒԜꜜͼⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟ᷄ᴐꜝꜜⱱ꞉ᴟꜛᴒᴑͼⱶⱨⱬͼԜᴡᴡԜᴐꞋͼᴟԜᴡᴒͼᴟԜᴡ꞉ꜝͼ꞉ᴠͼ᷈ͼӿꜜꜝᴑ꞉ⱱⱱᴒᴟᴒꜜᴐᴒͼ
ԝᴒᴡᴤᴒᴒꜜᴡᴟᴒԜᴡꜛᴒꜜᴡͼⱲᴟꜝᴢꜞᴠԐԓͼᴣᴒᴟᴠᴢᴠͼᴡⱳᴒͼԜꞌᴡᴒᴟꜜԜᴡ꞉ᴣᴒͼⱳᴦꜞꜝᴡⱳᴒᴠ꞉ᴠͼᴡⱳԜᴡͼᴡⱳᴒͼⱶⱨⱬͼԜᴡᴡԜᴐꞋͼᴟԜᴡᴒͼᴟԜᴡ꞉ꜝͼ꞉ᴠͼꜜꜝᴡͼ
᷈᷅ͼⱬᴠᴡ꞉ꜛԜᴡᴒᴑͼԜᴡᴡԜᴐꞋͼᴟԜᴡᴒͼᴟԜᴡ꞉ꜝᴠͼꞌᴒᴠᴠͼᴡⱳԜꜜͼꜝꜜᴒͼᴤꜝᴢꞌᴑͼ꞉ꜜᴑ꞉ᴐԜᴡᴒͼᴡⱳԜᴡͼᴠᴢԝ꞊ᴒᴐᴡᴠͼᴡᴟᴒԜᴡᴒᴑͼᴤ꞉ᴡⱳͼⱫᴅ᷄᷉Ⱡ᷊᷇ԓͼ
ꜝꜜͼԜᴣᴒᴟԜⱲᴒԓͼⱳԜᴣᴒͼԜͼꞌꜝᴤᴒᴟͼ꞉ꜜᴐ꞉ᴑᴒꜜᴐᴒͼꜝⱱͼⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟ᷄ᴐꜝꜜⱱ꞉ᴟꜛᴒᴑͼⱶⱨⱬͼԜᴡᴡԜᴐꞋᴠͼᴑᴢᴟ꞉ꜜⱲͼᴡⱳᴒͼᴒⱱⱱ꞉ᴐԜᴐᴦͼ
ᴒᴣԜꞌᴢԜᴡ꞉ꜝꜜͼꜞᴒᴟ꞉ꜝᴑ᷅ͼᴁⱳᴒͼⱳᴦꜞꜝᴡⱳᴒᴠ꞉ᴠͼᴤ꞉ꞌꞌͼԝᴒͼᴡᴒᴠᴡᴒᴑͼᴢᴠ꞉ꜜⱲͼᴡⱳᴒͼꜛꜝᴑᴒꞌ᷄ԝԜᴠᴒᴑͼꞌᴒԜᴠᴡͼᴠꜟᴢԜᴟᴒᴠͼꜛᴒԜꜜᴠͼ
ᴒᴠᴡ꞉ꜛԜᴡᴒͼꜝⱱͼᴡⱳᴒͼᴡᴟᴒԜᴡꜛᴒꜜᴡͼᴑ꞉ⱱⱱᴒᴟᴒꜜᴐᴒͼᴢᴠ꞉ꜜⱲͼԜͼᴄԜꞌᴑ᷄ԝԜᴠᴒᴑͼᴐⱳ꞉᷄ᴠꜟᴢԜᴟᴒͼᴡᴒᴠᴡ᷅
ᴁⱳᴒͼꜞᴒᴟᴐᴒꜜᴡԜⱲᴒͼᴐⱳԜꜜⱲᴒͼ꞉ꜜͼꜛᴒԜꜜͼⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟ᷄ᴐꜝꜜⱱ꞉ᴟꜛᴒᴑͼⱶⱨⱬͼԜᴡᴡԜᴐꞋͼᴟԜᴡᴒͼꜝⱱͼᴒԜᴐⱳͼԜᴐᴡ꞉ᴣᴒͼᴡᴟᴒԜᴡꜛᴒꜜᴡͼ
ⱲᴟꜝᴢꜞͼⱱᴟꜝꜛͼᴡⱳᴒͼԜᴡᴡԜᴐꞋͼᴟԜᴡᴒͼꜝⱱͼꜞꞌԜᴐᴒԝꜝͼᴤ꞉ꞌꞌͼԝᴒͼᴐԜꞌᴐᴢꞌԜᴡᴒᴑͼԜᴠͼ᷈᷇᷇ӼͼԑͼӿꜛᴒԜꜜͼᴟԜᴡᴒͼᴟԜᴡ꞉ꜝͼᶮ᷈Ԑ᷅ͼ
ᴀ꞉ꜛ꞉ꞌԜᴟꞌᴦԓͼᴡⱳᴒͼᴒᴠᴡ꞉ꜛԜᴡᴒᴑͼᴢꜞꜞᴒᴟͼԜꜜᴑͼꞌꜝᴤᴒᴟͼᴐꜝꜜⱱ꞉ᴑᴒꜜᴐᴒͼꞌ꞉ꜛ꞉ᴡᴠͼⱱꜝᴟͼᴡⱳᴒͼꜛᴒԜꜜͼᴟԜᴡᴒͼᴟԜᴡ꞉ꜝͼᴐԜꜜͼԝᴒͼ
ᴡᴟԜꜜᴠⱱꜝᴟꜛᴒᴑͼԝᴦͼᴠᴢԝᴡᴟԜᴐᴡ꞉ꜜⱲͼ᷈ͼԜꜜᴑͼꜛᴢꞌᴡ꞉ꜞꞌᴦ꞉ꜜⱲͼԝᴦͼ᷈᷇᷇ӼͼᴡꜝͼᴐԜꞌᴐᴢꞌԜᴡᴒͼⱠ᷿Ӽͼᴐꜝꜜⱱ꞉ᴑᴒꜜᴐᴒͼ꞉ꜜᴡᴒᴟᴣԜꞌᴠͼⱱꜝᴟͼ
ᴡⱳᴒͼꜞᴒᴟᴐᴒꜜᴡԜⱲᴒͼᴐⱳԜꜜⱲᴒ᷅ͼᴁⱳᴒͼꜛᴒԜꜜͼᴟԜᴡᴒͼᴟԜᴡ꞉ꜝᴠͼԜꜜᴑͼᴐꜝᴟᴟᴒᴠꜞꜝꜜᴑ꞉ꜜⱲͼⱠ᷿Ӽͼᴐꜝꜜⱱ꞉ᴑᴒꜜᴐᴒͼ꞉ꜜᴡᴒᴟᴣԜꞌᴠͼᴤ꞉ꞌꞌͼԝᴒͼ
ᴒᴠᴡ꞉ꜛԜᴡᴒᴑͼⱱᴟꜝꜛͼᴡⱳᴒͼⱲᴒꜜᴒᴟԜꞌ꞉ᴧᴒᴑͼꞌ꞉ꜜᴒԜᴟͼꜛꜝᴑᴒꞌͼԜᴠͼᴑᴒᴠᴐᴟ꞉ԝᴒᴑͼꜞᴟᴒᴣ꞉ꜝᴢᴠꞌᴦ᷅ͼ
ⱨꞌꞌͼᴒⱱⱱ꞉ᴐԜᴐᴦͼԜꜜԜꞌᴦᴠᴒᴠͼᴤ꞉ꞌꞌͼԝᴒͼᴐꜝꜜᴑᴢᴐᴡᴒᴑͼᴢᴠ꞉ꜜⱲͼᴡⱳᴒͼⱷᴁᴁͼꜞꜝꜞᴢꞌԜᴡ꞉ꜝꜜ᷅
ⱷꜜͼꜝᴟᴑᴒᴟͼᴡꜝͼꜛԜ꞉ꜜᴡԜ꞉ꜜͼᴡⱳᴒͼꜝᴣᴒᴟԜꞌꞌͼᴁᴦꜞᴒͼⱷͼᴒᴟᴟꜝᴟͼԜᴡͼ᷿᷇᷅᷇ԓͼԜͼᴐꜝꜜᴠᴒᴟᴣԜᴡ꞉ᴣᴒͼⱩꜝꜜⱱᴒᴟᴟꜝꜜ꞉᷄ԝԜᴠᴒᴑͼꜞᴟꜝᴐᴒᴑᴢᴟᴒͼ
ᴤ꞉ꞌꞌͼԝᴒͼᴢᴠᴒᴑͼⱱꜝᴟͼᴡⱳᴒͼᴐꜝꜛꜞԜᴟ꞉ᴠꜝꜜᴠͼꜝⱱͼᴒԜᴐⱳͼꜝⱱͼᴡⱳᴒͼԜᴐᴡ꞉ᴣᴒͼᴡᴟᴒԜᴡꜛᴒꜜᴡͼⱲᴟꜝᴢꜞᴠͼᴤ꞉ᴡⱳͼᴡⱳᴒͼꜞꞌԜᴐᴒԝꜝͼⱲᴟꜝᴢꜞͼ
ᴤ꞉ᴡⱳͼᴒꜟᴢԜꞌͼᴤᴒ꞉ⱲⱳᴡᴠͼⱱꜝᴟͼᴒԜᴐⱳͼᴡᴒᴠᴡͼᴠᴒᴡͼԜᴡͼ᷈᷅⅍ⅎӼ ᴠ꞉Ⱳꜜ꞉ⱱ꞉ᴐԜꜜᴐᴒͼꞌᴒᴣᴒꞌͼӿĮ᷊᷆Ԑ᷅
9.8.2 Secondary Efficacy Endpoints
ᴁⱳᴒͼᴟԜꜜꞋ᷄ꜝᴟᴑᴒᴟᴒᴑͼᴠᴒᴐꜝꜜᴑԜᴟᴦͼᴒⱱⱱ꞉ᴐԜᴐᴦͼᴒꜜᴑꜞꜝ꞉ꜜᴡᴠͼԜᴟᴒͼԜᴠͼⱱꜝꞌꞌꜝᴤᴠⱡ
᷈᷅꜠ᴢꜛԝᴒᴟͼꜝⱱͼⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟ᷄ᴐꜝꜜⱱ꞉ᴟꜛᴒᴑͼⱶⱨⱬͼԜᴡᴡԜᴐꞋᴠͼᴟᴒꜟᴢ꞉ᴟ꞉ꜜⱲͼԜᴐᴢᴡᴒͼᴡᴟᴒԜᴡꜛᴒꜜᴡͼᴑᴢᴟ꞉ꜜⱲͼᴡⱳᴒͼᴒⱱⱱ꞉ᴐԜᴐᴦͼ
ᴒᴣԜꞌᴢԜᴡ꞉ꜝꜜͼꜞᴒᴟ꞉ꜝᴑͼӿⱫԜᴦͼ᷇ͼᴡⱳᴟꜝᴢⱲⱳͼⱫԜᴦͼ᷈˲᷉Ԑ᷅
᷉᷅꜠ᴢꜛԝᴒᴟͼꜝⱱͼꜛꜝᴑᴒᴟԜᴡᴒͼꜝᴟͼᴠᴒᴣᴒᴟᴒͼⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟ᷄ᴐꜝꜜⱱ꞉ᴟꜛᴒᴑͼⱶⱨⱬͼԜᴡᴡԜᴐꞋᴠͼᴑᴢᴟ꞉ꜜⱲͼᴡⱳᴒͼᴒⱱⱱ꞉ᴐԜᴐᴦͼ
ᴒᴣԜꞌᴢԜᴡ꞉ꜝꜜͼꜞᴒᴟ꞉ꜝᴑͼӿⱫԜᴦͼ᷇ͼᴡⱳᴟꜝᴢⱲⱳͼⱫԜᴦͼ᷈˲᷉Ԑ᷅ͼ
᷊᷅꜠ᴢꜛԝᴒᴟͼꜝⱱͼⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟͼᴐꜝꜜⱱ꞉ᴟꜛᴒᴑͼⱶⱨⱬͼԜᴡᴡԜᴐꞋᴠͼꜝᴐᴐᴢᴟᴟ꞉ꜜⱲͼꜝꜜͼⱫԜᴦͼ᷈᷾ͼԜⱱᴡᴒᴟͼԜᴑꜛ꞉ꜜ꞉ᴠᴡᴟԜᴡ꞉ꜝꜜͼꜝⱱͼ
ᴠᴡᴢᴑᴦͼᴑᴟᴢⱲͼᴡⱳᴟꜝᴢⱲⱳͼⱫԜᴦͼ᷈˲᷉ͼӿⱫԜᴦͼ᷈᷾ͼᴡⱳᴟꜝᴢⱲⱳͼⱫԜᴦͼ᷈˲᷉Ԑ᷅

Ⱬᴅ᷄᷉Ⱡ᷊᷇
ⱪꞌ꞉ꜜ꞉ᴐԜꞌͼᴁᴟ꞉Ԝꞌͼ͟ᴟꜝᴡꜝᴐꜝꞌⱡͼⱫᴅ᷄᷉Ⱡ᷊᷊᷇᷄᷇
ⱨꜛᴒꜜᴑꜛᴒꜜᴡͼ᷊᷅᷇ͼⱴ꞉ꜜԜꞌⱡͼ᷇ⱠͼꜗԜꜜᴢԜᴟᴦ᷉᷇᷈ⅎ
ⱪꜝꜜⱱ꞉ᴑᴒꜜᴡ꞉Ԝꞌ
͟ԜⱲᴒͼ˲᷈
ⱫᴦԜᴥͼⱪꜝᴟꜞ᷅
ᴁⱳᴒͼᴠᴒᴐꜝꜜᴑԜᴟᴦͼᴒꜜᴑꜞꜝ꞉ꜜᴡᴠͼᴤ꞉ꞌꞌͼԝᴒͼԜꜜԜꞌᴦᴧᴒᴑͼᴢᴠ꞉ꜜⱲͼᴡⱳᴒͼᴠԜꜛᴒͼꜛᴒᴡⱳꜝᴑͼԜᴠͼᴑᴒᴠᴐᴟ꞉ԝᴒᴑͼⱱꜝᴟͼᴡⱳᴒͼꜞᴟ꞉ꜛԜᴟᴦͼ
ᴒⱱⱱ꞉ᴐԜᴐᴦͼᴒꜜᴑꜞꜝ꞉ꜜᴡ᷅ͼ
ᴁꜝͼԜᴑ꞊ᴢᴠᴡͼⱱꜝᴟͼᴡⱳᴒͼꜞꜝᴡᴒꜜᴡ꞉Ԝꞌͼꜝⱱͼ꞉ꜜⱱꞌԜᴡᴒᴑͼꜝᴣᴒᴟԜꞌꞌͼᴁᴦꜞᴒͼⱷͼᴒᴟᴟꜝᴟͼᴟԜᴡᴒԓͼᴡⱳᴒͼᴟԜꜜꞋͼꜝᴟᴑᴒᴟᴒᴑͼᴠᴒᴐꜝꜜᴑԜᴟᴦͼ
ᴒꜜᴑꜞꜝ꞉ꜜᴡᴠͼᴤ꞉ꞌꞌͼԝᴒͼᴡᴒᴠᴡᴒᴑͼ꞉ꜜͼԜͼⱱ꞉ᴥᴒᴑͼᴠᴒꜟᴢᴒꜜᴐᴒͼⱱꜝᴟͼᴒԜᴐⱳͼԜᴐᴡ꞉ᴣᴒͼᴡᴟᴒԜᴡꜛᴒꜜᴡͼⱲᴟꜝᴢꜞͼᴡꜝͼꜞꞌԜᴐᴒԝꜝͼⱲᴟꜝᴢꜞͼ
ᴐꜝꜛꜞԜᴟ꞉ᴠꜝꜜͼᴢᴠ꞉ꜜⱲͼԜͼⱲᴒꜜᴒᴟԜꞌͼⱲԜᴡᴒꞋᴒᴒꜞ꞉ꜜⱲͼԜꜞꜞᴟꜝԜᴐⱳͼᴐꜝꜜᴠ꞉ᴠᴡᴒꜜᴡͼᴤ꞉ᴡⱳͼᴡⱳᴒͼꞌꜝⱲ꞉ᴐԜꞌͼᴟᴒᴠᴡᴟ꞉ᴐᴡ꞉ꜝꜜᴠͼꜝⱱͼᴡⱳᴒͼ
ᴟԜꜜꞋͼꜝᴟᴑᴒᴟ꞉ꜜⱲͼꜝⱱͼᴡⱳᴒͼᴒꜜᴑꜞꜝ꞉ꜜᴡᴠ᷅ͼᴀᴒᴐꜝꜜᴑԜᴟᴦͼᴒꜜᴑꜞꜝ꞉ꜜᴡᴠͼᴤ꞉ꞌꞌͼꜜꜝᴡͼԝᴒͼᴑᴒᴐꞌԜᴟᴒᴑͼᴠᴡԜᴡ꞉ᴠᴡ꞉ᴐԜꞌꞌᴦͼᴠ꞉Ⱳꜜ꞉ⱱ꞉ᴐԜꜜᴡͼ
ᴢꜜꞌᴒᴠᴠͼᴡⱳᴒͼꜞᴟ꞉ꜛԜᴟᴦͼᴒꜜᴑꜞꜝ꞉ꜜᴡͼⱱꜝᴟͼᴡⱳԜᴡͼԜᴐᴡ꞉ᴣᴒͼᴡᴟᴒԜᴡꜛᴒꜜᴡͼⱲᴟꜝᴢꜞͼᴡꜝͼꜞꞌԜᴐᴒԝꜝͼⱲᴟꜝᴢꜞͼᴐꜝꜛꜞԜᴟ꞉ᴠꜝꜜͼ꞉ᴠͼⱱꜝᴢꜜᴑͼ
ᴡꜝͼԝᴒͼᴠᴡԜᴡ꞉ᴠᴡ꞉ᴐԜꞌꞌᴦͼᴠ꞉Ⱳꜜ꞉ⱱ꞉ᴐԜꜜᴡ᷅ͼᴁⱳᴒͼᴡᴒᴠᴡ꞉ꜜⱲͼꜞᴟꜝᴐᴒᴑᴢᴟᴒͼ꞉ᴠͼᴑᴒᴡԜ꞉ꞌᴒᴑͼ꞉ꜜͼᴀᴒᴐᴡ꞉ꜝꜜⱠ᷿᷅᷈᷉᷅᷅
9.8.3 Exploratory Efficacy Endpoints
ᴁⱳᴒͼᴒᴥꜞꞌꜝᴟԜᴡꜝᴟᴦͼᴒⱱⱱ꞉ᴐԜᴐᴦͼᴒꜜᴑꜞꜝ꞉ꜜᴡᴠͼ꞉ꜜᴐꞌᴢᴑᴒⱡ

ᴁ꞉ꜛᴒͼᴡꜝͼⱱ꞉ᴟᴠᴡͼⱶⱨⱬͼԜᴡᴡԜᴐꞋͼԜⱱᴡᴒᴟͼⱫԜᴦͼ᷈᷾ԓͼ꞉᷅ᴒ᷅ԓͼᴑᴢᴟԜᴡ꞉ꜝꜜͼᴡⱳԜᴡͼԜͼᴠᴢԝ꞊ᴒᴐᴡͼ꞉ᴠͼԜᴡᴡԜᴐꞋ᷄ⱱᴟᴒᴒͼԜⱱᴡᴒᴟͼⱫԜᴦ᷈᷾

꜠ᴢꜛԝᴒᴟͼꜝⱱͼⱳ꞉Ⱳⱳ᷄ꜛꜝᴟԝ꞉ᴑ꞉ᴡᴦͼⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟ᷄ᴐꜝꜜⱱ꞉ᴟꜛᴒᴑͼⱶⱨⱬͼԜᴡᴡԜᴐꞋᴠͼᴑᴢᴟ꞉ꜜⱲͼᴡⱳᴒͼᴒⱱⱱ꞉ᴐԜᴐᴦͼ
ᴒᴣԜꞌᴢԜᴡ꞉ꜝꜜͼꜞᴒᴟ꞉ꜝᴑⱢͼԜͼⱳ꞉Ⱳⱳ᷄ꜛꜝᴟԝ꞉ᴑ꞉ᴡᴦͼⱶⱨⱬͼԜᴡᴡԜᴐꞋͼ꞉ᴠͼᴑᴒⱱ꞉ꜜᴒᴑͼԜᴠͼԜꜜᴦͼԜᴡᴡԜᴐꞋͼᴡⱳԜᴡͼⱳԜᴠͼԜᴡͼꞌᴒԜᴠᴡͼꜝꜜᴒͼ
ꜝⱱͼᴡⱳᴒͼⱱꜝꞌꞌꜝᴤ꞉ꜜⱲͼᴐⱳԜᴟԜᴐᴡᴒᴟ꞉ᴠᴡ꞉ᴐᴠⱡͼᴠᴒᴣᴒᴟᴒԓͼᴟᴒᴠᴢꞌᴡᴠͼ꞉ꜜͼⱳꜝᴠꜞ꞉ᴡԜꞌ꞉ᴧԜᴡ꞉ꜝꜜͼӿᴒᴥᴐᴒꜞᴡͼⱳꜝᴠꜞ꞉ᴡԜꞌ꞉ᴧԜᴡ꞉ꜝꜜͼⱱꜝᴟͼ
ꜝԝᴠᴒᴟᴣԜᴡ꞉ꜝꜜͼⱣͼ᷉᷾ͼⱳꜝᴢᴟᴠԐԓͼⱳᴒꜛꜝᴑᴦꜜԜꜛ꞉ᴐԜꞌꞌᴦͼᴠ꞉Ⱳꜜ꞉ⱱ꞉ᴐԜꜜᴡͼӿᴠᴦᴠᴡꜝꞌ꞉ᴐͼԝꞌꜝꜝᴑͼꜞᴟᴒᴠᴠᴢᴟᴒͼⱣͼⱠ᷇ԓͼᴟᴒꜟᴢ꞉ᴟᴒᴠͼ
ⱷᴃͼⱳᴦᴑᴟԜᴡ꞉ꜝꜜԓͼꜝᴟͼԜᴠᴠꜝᴐ꞉Ԝᴡᴒᴑͼᴤ꞉ᴡⱳͼᴠᴦꜜᴐꜝꜞᴒͼꜝᴟͼꜜᴒԜᴟ᷄ᴠᴦꜜᴐꜝꜞᴒԐͼꜝᴟͼꞌԜᴟᴦꜜⱲᴒԜꞌ᷅
ᴁⱳᴒͼᴒᴥꜞꞌꜝᴟԜᴡꜝᴟᴦͼᴒⱱⱱ꞉ᴐԜᴐᴦͼᴒꜜᴑꜞꜝ꞉ꜜᴡᴠͼԜᴟᴒͼᴐꜝꜜᴠ꞉ᴑᴒᴟᴒᴑͼᴠᴢꜞꜞꜝᴟᴡ꞉ᴣᴒͼԜꜜᴑͼԜꜜᴦͼᴠᴡԜᴡ꞉ᴠᴡ꞉ᴐԜꞌͼᴡᴒᴠᴡᴠͼᴐꜝꜛꜞԜᴟ꞉ꜜⱲͼ
ᴡᴟᴒԜᴡꜛᴒꜜᴡᴠͼᴤ꞉ꞌꞌͼԝᴒͼꜛԜᴑᴒͼᴤ꞉ᴡⱳꜝᴢᴡͼԜᴑ꞊ᴢᴠᴡꜛᴒꜜᴡͼⱱꜝᴟͼꜛᴢꞌᴡ꞉ꜞꞌ꞉ᴐ꞉ᴡᴦ᷅ͼᴁⱳᴒͼᴟᴒᴠᴢꞌᴡ꞉ꜜⱲͼꜞ᷄ᴣԜꞌᴢᴒᴠͼⱱᴟꜝꜛͼᴡⱳᴒᴠᴒͼ
ᴠᴢꜞꜞꜝᴟᴡ꞉ᴣᴒͼԜꜜԜꞌᴦᴠᴒᴠͼᴤ꞉ꞌꞌͼԝᴒͼ꞉ꜜᴡᴒᴟꜞᴟᴒᴡᴒᴑͼᴑᴒᴠᴐᴟ꞉ꜞᴡ꞉ᴣᴒꞌᴦͼԜᴠͼᴠᴢꜛꜛԜᴟ꞉ᴧ꞉ꜜⱲͼᴡⱳᴒͼᴤᴒ꞉Ⱳⱳᴡͼꜝⱱͼᴒᴣ꞉ᴑᴒꜜᴐᴒͼⱱꜝᴟͼԜͼ
ᴡᴟᴒԜᴡꜛᴒꜜᴡͼᴒⱱⱱᴒᴐᴡ᷅
9.9
Analysis of Pharmacokinetic and Pharmacodynamic Endpoints
9.9.1
Pharmacokinetic Assessments:
ⱩꞌꜝꜝᴑͼᴠԜꜛꜞꞌᴒᴠͼᴤ꞉ꞌꞌͼԝᴒͼᴐꜝꞌꞌᴒᴐᴡᴒᴑͼⱱꜝᴟͼᴡⱳᴒͼꜛᴒԜᴠᴢᴟᴒꜛᴒꜜᴡͼꜝⱱͼꜞꞌԜᴠꜛԜͼⱫᴅ᷄᷉Ⱡ᷊᷇ͼᴐꜝꜜᴐᴒꜜᴡᴟԜᴡ꞉ꜝꜜᴠͼꜞᴟ꞉ꜝᴟͼᴡꜝͼ
ⱷꜚ͟ͼԜᴑꜛ꞉ꜜ꞉ᴠᴡᴟԜᴡ꞉ꜝꜜͼꜝꜜͼⱫԜᴦͼ᷇ͼԜꜜᴑͼꜝꜜͼⱫԜᴦᴠͼ᷿⅍ᶐ᷊ԓͼⱠ˲ᶐ᷊ԓͼ᷈᷾᷇ᶐ᷊ͼԜꜜᴑͼ᷈˲᷉ᶐ᷊᷅ͼⱨᴑᴑ꞉ᴡ꞉ꜝꜜԜꞌͼᴠԜꜛꜞꞌᴒᴠͼ
ᴤ꞉ꞌꞌͼԝᴒͼᴐꜝꞌꞌᴒᴐᴡᴒᴑͼꜝꜜͼⱫԜᴦᴠͼ᷉᷈᷇ᶐ᷊ԓͼԜꜜᴑͼ᷊᷉˲ᶐ᷊ͼᴑᴢᴟ꞉ꜜⱲͼᴡⱳᴒͼⱱꜝꞌꞌꜝᴤ᷄ᴢꜞͼꜞᴒᴟ꞉ꜝᴑͼⱱꜝᴟͼԜꜜᴦͼᴠᴢԝ꞊ᴒᴐᴡᴠͼꜜꜝᴡͼ
ᴒꜜᴡᴒᴟ꞉ꜜⱲͼ꜡ꜙⱬ᷅
͟ꞌԜᴠꜛԜͼᴐꜝꜜᴐᴒꜜᴡᴟԜᴡ꞉ꜝꜜᴠͼꜝⱱͼⱫᴅ᷄᷉Ⱡ᷊᷇ͼᴤ꞉ꞌꞌͼԝᴒͼᴠᴢꜛꜛԜᴟ꞉ᴧᴒᴑͼᴤ꞉ᴡⱳͼᴑᴒᴠᴐᴟ꞉ꜞᴡ꞉ᴣᴒͼᴠᴡԜᴡ꞉ᴠᴡ꞉ᴐᴠͼԝᴦͼꜜꜝꜛ꞉ꜜԜꞌͼ͟ꜘͼ
ᴠԜꜛꜞꞌ꞉ꜜⱲͼᴡ꞉ꜛᴒ᷅
9.9.2
Pharmacodynamic Assessments:
ⱩꞌꜝꜝᴑͼᴠԜꜛꜞꞌᴒᴠͼᴤ꞉ꞌꞌͼԝᴒͼᴐꜝꞌꞌᴒᴐᴡᴒᴑͼᴡꜝͼᴒᴣԜꞌᴢԜᴡᴒͼᴡⱳᴒͼꜞⱳԜᴟꜛԜᴐꜝᴑᴦꜜԜꜛ꞉ᴐͼᴒⱱⱱᴒᴐᴡᴠͼꜝⱱͼⱫᴅ᷄᷉Ⱡ᷊᷇ͼᴡⱳᴟꜝᴢⱲⱳͼ
ԝ꞉ꜝꜛԜᴟꞋᴒᴟͼԜᴠᴠԜᴦᴠͼꜞᴟ꞉ꜝᴟͼᴡꜝͼⱷꜚ͟ͼԜᴑꜛ꞉ꜜ꞉ᴠᴡᴟԜᴡ꞉ꜝꜜͼꜝꜜͼⱫԜᴦͼ᷇ͼԜꜜᴑͼꜝꜜͼⱫԜᴦᴠͼ᷿⅍ᶐ᷊ԓͼⱠ˲ᶐ᷊ԓͼ᷈᷾᷇ᶐ᷊ԓͼԜꜜᴑͼ
᷈˲᷉ᶐ᷊᷅ͼⱨᴑᴑ꞉ᴡ꞉ꜝꜜԜꞌͼᴠԜꜛꜞꞌᴒᴠͼᴤ꞉ꞌꞌͼԝᴒͼᴐꜝꞌꞌᴒᴐᴡᴒᴑͼꜝꜜͼⱫԜᴦᴠͼ᷉᷈᷇ᶐ᷊ԓͼԜꜜᴑͼ᷊᷉˲ᶐ᷊ͼᴑᴢᴟ꞉ꜜⱲͼᴡⱳᴒͼⱱꜝꞌꞌꜝᴤ᷄ᴢꜞͼ
ꜞᴒᴟ꞉ꜝᴑͼⱱꜝᴟͼԜꜜᴦͼᴠᴢԝ꞊ᴒᴐᴡᴠͼꜜꜝᴡͼᴒꜜᴡᴒᴟ꞉ꜜⱲͼ꜡ꜙⱬ᷅

Ⱬᴅ᷄᷉Ⱡ᷊᷇
ⱪꞌ꞉ꜜ꞉ᴐԜꞌͼᴁᴟ꞉Ԝꞌͼ͟ᴟꜝᴡꜝᴐꜝꞌⱡͼⱫᴅ᷄᷉Ⱡ᷊᷊᷇᷄᷇
ⱨꜛᴒꜜᴑꜛᴒꜜᴡͼ᷊᷅᷇ͼⱴ꞉ꜜԜꞌⱡͼ᷇ⱠͼꜗԜꜜᴢԜᴟᴦ᷉᷇᷈ⅎ
ⱪꜝꜜⱱ꞉ᴑᴒꜜᴡ꞉Ԝꞌ
͟ԜⱲᴒͼ˲᷉
ⱫᴦԜᴥͼⱪꜝᴟꜞ᷅
͟ꞌԜᴠꜛԜͼꞋԜꞌꞌ꞉Ꞌᴟᴒ꞉ꜜͼԜᴐᴡ꞉ᴣ꞉ᴡᴦͼᴤ꞉ꞌꞌͼԝᴒͼᴠᴢꜛꜛԜᴟ꞉ᴧᴒᴑͼᴤ꞉ᴡⱳͼᴑᴒᴠᴐᴟ꞉ꜞᴡ꞉ᴣᴒͼᴠᴡԜᴡ꞉ᴠᴡ꞉ᴐᴠͼԝᴦͼꜜꜝꜛ꞉ꜜԜꞌͼ͟ⱫͼᴠԜꜛꜞꞌ꞉ꜜⱲͼ
ᴡ꞉ꜛᴒ᷅
9.9.3
Immunogenicity Assessments:
ⱩꞌꜝꜝᴑͼᴠԜꜛꜞꞌᴒᴠͼᴤ꞉ꞌꞌͼԝᴒͼᴐꜝꞌꞌᴒᴐᴡᴒᴑͼᴡꜝͼԜᴠᴠԜᴦͼⱱꜝᴟͼᴡⱳᴒͼꜞᴟᴒᴠᴒꜜᴐᴒͼꜝⱱͼԜꜜᴡ꞉᷄ᴑᴟᴢⱲͼԜꜜᴡ꞉ԝꜝᴑ꞉ᴒᴠԓͼ꞉ꜜᴐꞌᴢᴑ꞉ꜜⱲͼ
ᴒᴣԜꞌᴢԜᴡ꞉ꜝꜜͼꜝⱱͼꜜᴒᴢᴡᴟԜꞌ꞉ᴧ꞉ꜜⱲͼԜꜜᴡ꞉ԝꜝᴑ꞉ᴒᴠͼӿ꞉ⱱͼԜꜜᴦͼᴐꜝꜜⱱ꞉ᴟꜛᴒᴑͼꜞꜝᴠ꞉ᴡ꞉ᴣᴒͼԜꜜᴡ꞉᷄ᴑᴟᴢⱲͼԜꜜᴡ꞉ԝꜝᴑ꞉ᴒᴠͼԜᴟᴒͼᴑᴒᴡᴒᴐᴡᴒᴑԐͼ
ꜞᴟ꞉ꜝᴟͼᴡꜝͼⱷꜚ͟ͼԜᴑꜛ꞉ꜜ꞉ᴠᴡᴟԜᴡ꞉ꜝꜜͼꜝꜜͼⱫԜᴦͼ᷇ͼԜꜜᴑͼꜝꜜͼⱫԜᴦᴠͼ᷿⅍ᶐ᷊ԓͼⱠ˲ᶐ᷊ԓͼ᷈᷾᷇ᶐ᷊ԓͼԜꜜᴑͼ᷈˲᷉ᶐ᷊᷅ͼⱨᴑᴑ꞉ᴡ꞉ꜝꜜԜꞌͼ
ᴠԜꜛꜞꞌᴒᴠͼᴤ꞉ꞌꞌͼԝᴒͼᴐꜝꞌꞌᴒᴐᴡᴒᴑͼꜝꜜͼⱫԜᴦͼ᷊᷉˲ᶐ᷊ͼᴑᴢᴟ꞉ꜜⱲͼᴡⱳᴒͼⱱꜝꞌꞌꜝᴤ᷄ᴢꜞͼꜞᴒᴟ꞉ꜝᴑͼⱱꜝᴟͼԜꜜᴦͼᴠᴢԝ꞊ᴒᴐᴡᴠͼꜜꜝᴡͼ
ᴒꜜᴡᴒᴟ꞉ꜜⱲͼ꜡ꜙⱬ
9.9.4
C1-INH and C4 Assessments:
ᴀԜꜛꜞꞌᴒᴠͼᴤ꞉ꞌꞌͼԝᴒͼꜝԝᴡԜ꞉ꜜᴒᴑͼⱱꜝᴟͼⱪ᷈᷄ⱷ꜠ⱶԓͼⱪ᷾ͼԜꜜᴑͼⱪ᷈ꜟͼԜᴠᴠԜᴦᴠͼԜᴡͼᴠᴐᴟᴒᴒꜜ꞉ꜜⱲͼⱱꜝᴟͼᴒꞌ꞉Ⱳ꞉ԝ꞉ꞌ꞉ᴡᴦͼԜᴠᴠᴒᴠᴠꜛᴒꜜᴡ᷅
9.10
Safety Analysis
ᴁᴟᴒԜᴡꜛᴒꜜᴡ᷄ᴒꜛᴒᴟⱲᴒꜜᴡͼⱨⱬᴠͼԜᴟᴒͼᴑᴒⱱ꞉ꜜᴒᴑͼԜᴠͼⱨⱬᴠͼᴤ꞉ᴡⱳͼꜝꜜᴠᴒᴡͼԜᴡͼᴡⱳᴒͼᴡ꞉ꜛᴒͼꜝⱱͼꜝᴟͼⱱꜝꞌꞌꜝᴤ꞉ꜜⱲͼᴡⱳᴒͼᴠᴡԜᴟᴡͼꜝⱱͼ
ᴡᴟᴒԜᴡꜛᴒꜜᴡͼᴤ꞉ᴡⱳͼᴠᴡᴢᴑᴦͼꜛᴒᴑ꞉ᴐԜᴡ꞉ꜝꜜԓͼꜝᴟͼꜛᴒᴑ꞉ᴐԜꞌͼᴐꜝꜜᴑ꞉ᴡ꞉ꜝꜜᴠͼꜞᴟᴒᴠᴒꜜᴡͼꜞᴟ꞉ꜝᴟͼᴡꜝͼᴡⱳᴒͼᴠᴡԜᴟᴡͼꜝⱱͼᴡᴟᴒԜᴡꜛᴒꜜᴡͼԝᴢᴡͼ
꞉ꜜᴐᴟᴒԜᴠ꞉ꜜⱲͼ꞉ꜜͼᴠᴒᴣᴒᴟ꞉ᴡᴦͼꜝᴟͼᴟᴒꞌԜᴡ꞉ꜝꜜᴠⱳ꞉ꜞͼԜᴡͼᴡⱳᴒͼᴡ꞉ꜛᴒͼꜝⱱͼꜝᴟͼⱱꜝꞌꞌꜝᴤ꞉ꜜⱲͼᴡⱳᴒͼᴠᴡԜᴟᴡͼꜝⱱͼᴡᴟᴒԜᴡꜛᴒꜜᴡ᷅ͼᴁⱳᴒͼ
ꜜᴢꜛԝᴒᴟͼԜꜜᴑͼꜞᴒᴟᴐᴒꜜᴡԜⱲᴒͼꜝⱱͼᴠᴢԝ꞊ᴒᴐᴡᴠͼᴤ꞉ᴡⱳͼᴁⱬⱨⱬᴠͼᴤ꞉ꞌꞌͼԝᴒͼᴑ꞉ᴠꜞꞌԜᴦᴒᴑͼⱱꜝᴟͼᴒԜᴐⱳͼᴡᴟᴒԜᴡꜛᴒꜜᴡͼⱲᴟꜝᴢꜞͼԝᴦͼ
ԝꜝᴑᴦͼᴠᴦᴠᴡᴒꜛͼԜꜜᴑͼꜞᴟᴒⱱᴒᴟᴟᴒᴑͼᴡᴒᴟꜛͼᴢᴠ꞉ꜜⱲͼᴡⱳᴒͼꜚᴒᴑ꞉ᴐԜꞌͼⱫ꞉ᴐᴡ꞉ꜝꜜԜᴟᴦͼⱱꜝᴟͼϸᴒⱲᴢꞌԜᴡꜝᴟᴦͼⱨᴐᴡ꞉ᴣ꞉ᴡ꞉ᴒᴠͼ
ӿꜚᴒᴑⱫϸⱨᶇԐ᷅ͼᴀᴢꜛꜛԜᴟ꞉ᴒᴠͼ꞉ꜜͼᴡᴒᴟꜛᴠͼꜝⱱͼᴠᴒᴣᴒᴟ꞉ᴡᴦͼԜꜜᴑͼᴟᴒꞌԜᴡ꞉ꜝꜜᴠⱳ꞉ꜞͼᴡꜝͼᴠᴡᴢᴑᴦͼꜛᴒᴑ꞉ᴐԜᴡ꞉ꜝꜜͼᴤ꞉ꞌꞌͼԜꞌᴠꜝͼԝᴒͼ
ꜞᴟꜝᴣ꞉ᴑᴒᴑ᷅ͼᴀᴒᴟ꞉ꜝᴢᴠͼⱨⱬᴠͼᴤ꞉ꞌꞌͼԝᴒͼᴠᴢꜛꜛԜᴟ꞉ᴧᴒᴑͼᴠᴒꜞԜᴟԜᴡᴒꞌᴦͼ꞉ꜜͼԜͼᴠ꞉ꜛ꞉ꞌԜᴟͼⱱԜᴠⱳ꞉ꜝꜜ᷅ͼ͟Ԝᴡ꞉ᴒꜜᴡͼꞌ꞉ᴠᴡ꞉ꜜⱲᴠͼꜝⱱͼⱨⱬᴠͼ
ᴐԜᴢᴠ꞉ꜜⱲͼᴑ꞉ᴠᴐꜝꜜᴡ꞉ꜜᴢԜᴡ꞉ꜝꜜͼꜝⱱͼᴠᴡᴢᴑᴦͼꜛᴒᴑ꞉ᴐԜᴡ꞉ꜝꜜԓͼⱨⱬᴠͼꞌᴒԜᴑ꞉ꜜⱲͼᴡꜝͼᴑᴒԜᴡⱳԓͼᴀⱨⱬᴠͼԜꜜᴑͼⱨⱬᴀⱷͼᴤ꞉ꞌꞌͼԝᴒͼ
ꜞᴟꜝᴑᴢᴐᴒᴑ᷅
ⱨⱬᴀⱷͼᴤ꞉ꞌꞌͼԝᴒͼԜꜜԜꞌᴦᴧᴒᴑͼԜᴐᴐꜝᴟᴑ꞉ꜜⱲͼᴡꜝͼꜞᴟ꞉ꜛԜᴟᴦͼᴠᴦᴠᴡᴒꜛͼ꜡ᴟⱲԜꜜͼⱪꞌԜᴠᴠᴒᴠͼӿᴀ꜡ⱪᴠԐͼԜꜜᴑͼ͟ᴟᴒⱱᴒᴟᴟᴒᴑͼᴁᴒᴟꜛᴠͼ
ӿ͟ᴁᴠԐͼᴑᴒᴡᴒᴟꜛ꞉ꜜᴒᴑͼԝᴦͼᴡⱳᴒͼᴠᴒԜᴟᴐⱳꜝⱱᴟᴒꞌᴒᴣԜꜜᴡᴀᴡԜꜜᴑԜᴟᴑ꞉ᴧᴒᴑͼꜚᴒᴑⱫϸⱨϷᴢᴒᴟ꞉ᴒᴠӿᴀꜚϷᴠԐ᷅ͼᴀᴢꜛꜛԜᴟᴦͼ
ᴡԜԝꞌᴒᴠͼᴤ꞉ᴡⱳͼᴀ꜡ⱪᴠͼԜꜜᴑ͟ᴁᴠԓͼⱱᴟꜝꜛͼᴡⱳᴒͼᴀꜚϷ ᴠᴒԜᴟᴐⱳᴒᴠԓ ᴤ꞉ꞌꞌͼԝᴒͼⱲᴒꜜᴒᴟԜᴡᴒᴑͼꜞᴟᴒᴠᴒꜜᴡ꞉ꜜⱲᴡⱳᴒͼꜜᴢꜛԝᴒᴟͼԜꜜᴑͼ
ꜞᴒᴟᴐᴒꜜᴡԜⱲᴒͼꜝⱱͼᴠᴢԝ꞊ᴒᴐᴡᴠͼԝᴦͼⱨⱬԓͼᴠᴒᴣᴒᴟ꞉ᴡᴦԓͼᴠᴒᴟ꞉ꜝᴢᴠꜜᴒᴠᴠԓͼԜꜜᴑͼᴟᴒꞌԜᴡ꞉ꜝꜜᴠⱳ꞉ꜞͼᴡꜝͼᴠᴡᴢᴑᴦͼꜛᴒᴑ꞉ᴐԜᴡ꞉ꜝꜜ᷅
ᴂᴠԜⱲᴒͼꜝⱱͼᴐꜝꜜᴐꜝꜛ꞉ᴡԜꜜᴡͼꜛᴒᴑ꞉ᴐԜᴡ꞉ꜝꜜᴠͼӿꜝᴡⱳᴒᴟͼᴡⱳԜꜜͼᴟᴒᴠᴐᴢᴒͼꜛᴒᴑ꞉ᴐԜᴡ꞉ꜝꜜᴠԐͼᴤ꞉ꞌꞌͼԝᴒͼᴠᴢꜛꜛԜᴟ꞉ᴧᴒᴑͼ
ᴑᴒᴠᴐᴟ꞉ꜞᴡ꞉ᴣᴒꞌᴦͼⱱꜝᴟͼᴒԜᴐⱳͼꜝⱱͼᴡⱳᴒͼᴡᴟᴒԜᴡꜛᴒꜜᴡͼⱲᴟꜝᴢꜞᴠͼԜꜜᴑͼᴡⱳᴒͼᴐꜝꜛԝ꞉ꜜᴒᴑԜᴐᴡ꞉ᴣᴒͼᴡᴟᴒԜᴡꜛᴒꜜᴡͼⱲᴟꜝᴢꜞ᷅
ⱨᴐᴡᴢԜꞌͼᴣԜꞌᴢᴒᴠͼԜꜜᴑͼᴐⱳԜꜜⱲᴒͼⱱᴟꜝꜛͼᴠᴐᴟᴒᴒꜜ꞉ꜜⱲͼ꞉ꜜͼᴣ꞉ᴡԜꞌͼᴠ꞉ⱲꜜᴠͼԜꜜᴑͼᴐꞌ꞉ꜜ꞉ᴐԜꞌͼꞌԜԝꜝᴟԜᴡꜝᴟᴦͼᴡᴒᴠᴡᴠͼᴤ꞉ꞌꞌͼԝᴒͼ
ᴠᴢꜛꜛԜᴟ꞉ᴧᴒᴑͼⱱꜝᴟͼᴒԜᴐⱳͼᴡᴟᴒԜᴡꜛᴒꜜᴡͼⱲᴟꜝᴢꜞͼᴤ꞉ᴡⱳͼᴑᴒᴠᴐᴟ꞉ꜞᴡ꞉ᴣᴒͼᴠᴡԜᴡ꞉ᴠᴡ꞉ᴐᴠͼԜᴡͼᴒԜᴐⱳͼԜᴠᴠᴒᴠᴠꜛᴒꜜᴡͼꜝԝᴡԜ꞉ꜜᴒᴑ᷅ͼⱴꜝᴟͼ
ԜꞌꞌͼꞌԜԝꜝᴟԜᴡꜝᴟᴦͼᴡᴒᴠᴡᴠԓͼԜͼᴠⱳ꞉ⱱᴡͼᴡԜԝꞌᴒͼᴤ꞉ꞌꞌͼԝᴒͼꜞᴟꜝᴑᴢᴐᴒᴑͼᴠᴢꜛꜛԜᴟ꞉ᴧ꞉ꜜⱲͼᴐⱳԜꜜⱲᴒᴠͼⱱᴟꜝꜛͼꜜꜝᴟꜛԜꞌͼᴡꜝͼԜԝꜜꜝᴟꜛԜꞌͼ
Ԝꜜᴑͼᴣ꞉ᴐᴒ᷄ᴣᴒᴟᴠԜ᷅
ⱨԝꜜꜝᴟꜛԜꞌͼꜞⱳᴦᴠ꞉ᴐԜꞌͼᴒᴥԜꜛ꞉ꜜԜᴡ꞉ꜝꜜͼⱱ꞉ꜜᴑ꞉ꜜⱲᴠͼᴤ꞉ꞌꞌͼԝᴒͼꞌ꞉ᴠᴡᴒᴑ᷅
ᴁⱳᴒͼꜜᴢꜛԝᴒᴟͼԜꜜᴑͼꜞᴒᴟᴐᴒꜜᴡԜⱲᴒͼꜝⱱͼᴠᴢԝ꞊ᴒᴐᴡᴠͼᴤ꞉ᴡⱳͼꜜꜝᴟꜛԜꞌԓͼԜԝꜜꜝᴟꜛԜꞌ᷄ꜜꜝᴡͼᴐꞌ꞉ꜜ꞉ᴐԜꞌꞌᴦͼᴠ꞉Ⱳꜜ꞉ⱱ꞉ᴐԜꜜᴡԓͼԜꜜᴑͼ
ԜԝꜜꜝᴟꜛԜꞌ᷄ᴐꞌ꞉ꜜ꞉ᴐԜꞌꞌᴦͼᴠ꞉Ⱳꜜ꞉ⱱ꞉ᴐԜꜜᴡͼⱬⱪⱵͼⱱ꞉ꜜᴑ꞉ꜜⱲᴠͼᴤ꞉ꞌꞌͼԝᴒͼᴑ꞉ᴠꜞꞌԜᴦᴒᴑͼⱱꜝᴟͼᴒԜᴐⱳͼꜝⱱͼᴡⱳᴒͼᴡᴟᴒԜᴡꜛᴒꜜᴡͼⱲᴟꜝᴢꜞᴠ᷅
ⱨᴑᴑ꞉ᴡ꞉ꜝꜜԜꞌͼԜꜜԜꞌᴦᴠᴒᴠͼꜝⱱͼⱨⱬᴠԓͼᴀⱨⱬᴠԓͼᴠᴒᴣᴒᴟᴒͼⱨⱬᴠԓͼⱨⱬᴀⱷԓͼԜꜜᴑͼԜԝꜜꜝᴟꜛԜꞌͼⱱ꞉ꜜᴑ꞉ꜜⱲᴠͼᴤ꞉ꞌꞌͼԝᴒͼԝԜᴠᴒᴑͼꜝꜜͼ
ᴡⱳᴒͼᴡ꞉ꜛ꞉ꜜⱲͼӿᴀᴡᴢᴑᴦͼⱫԜᴦԐͼԜꜜᴑͼꜜᴢꜛԝᴒᴟͼꜝⱱͼꜞᴟ꞉ꜝᴟͼᴑꜝᴠᴒᴠͼꜝⱱͼᴠᴡᴢᴑᴦͼꜛᴒᴑ꞉ᴐԜᴡ꞉ꜝꜜ᷅ͼᴁⱳᴒͼ꞉ꜜᴐ꞉ᴑᴒꜜᴐᴒͼꜝⱱͼⱨⱬᴠͼԝᴦͼ

Ⱬᴅ᷄᷉Ⱡ᷊᷇
ⱪꞌ꞉ꜜ꞉ᴐԜꞌͼᴁᴟ꞉Ԝꞌͼ͟ᴟꜝᴡꜝᴐꜝꞌⱡͼⱫᴅ᷄᷉Ⱡ᷊᷊᷇᷄᷇
ⱨꜛᴒꜜᴑꜛᴒꜜᴡͼ᷊᷅᷇ͼⱴ꞉ꜜԜꞌⱡͼ᷇ⱠͼꜗԜꜜᴢԜᴟᴦ᷉᷇᷈ⅎ
ⱪꜝꜜⱱ꞉ᴑᴒꜜᴡ꞉Ԝꞌ
͟ԜⱲᴒͼ˲᷊
ⱫᴦԜᴥͼⱪꜝᴟꜞ᷅
ꜛꜝꜜᴡⱳͼⱱᴟꜝꜛᴡⱳᴒͼᴠᴡԜᴟᴡͼꜝⱱͼᴠᴡᴢᴑᴦͼꜛᴒᴑ꞉ᴐԜᴡ꞉ꜝꜜͼᴤ꞉ꞌꞌͼԝᴒͼᴒᴥԜꜛ꞉ꜜᴒᴑͼԜꜜᴑͼᴡⱳᴒͼ꞉ꜜᴐ꞉ᴑᴒꜜᴐᴒͼԜꜛꜝꜜⱲͼᴡⱳᴒͼⱱꜝᴢᴟͼ
ᴡᴟᴒԜᴡꜛᴒꜜᴡͼԜᴟꜛᴠͼᴤ꞉ꞌꞌͼԝᴒͼᴐꜝꜛꜞԜᴟᴒᴑ᷅ͼᴁⱳᴒͼᴟԜᴡᴒͼꜝⱱͼᴠᴡᴢᴑᴦͼᴑ꞉ᴠᴐꜝꜜᴡ꞉ꜜᴢԜᴡ꞉ꜝꜜͼԜꜛꜝꜜⱲͼᴡⱳᴒͼⱱꜝᴢᴟͼᴡᴟᴒԜᴡꜛᴒꜜᴡͼ
Ԝᴟꜛᴠͼᴤ꞉ꞌꞌͼԜꞌᴠꜝͼԝᴒͼᴐꜝꜛꜞԜᴟᴒᴑ᷅ͼ
9.11
Analysis of Quality of Life Assessments
ϷᴢԜꞌ꞉ᴡᴦͼꜝⱱͼꞌ꞉ⱱᴒͼᴑԜᴡԜͼᴤ꞉ꞌꞌͼԝᴒͼꜝԝᴡԜ꞉ꜜᴒᴑͼᴢᴠ꞉ꜜⱲͼᴡⱳᴒͼⱬϷ᷿ⱫͼϷᴢᴒᴠᴡ꞉ꜝꜜꜜԜ꞉ᴟᴒͼԜᴡͼꜞᴟᴒ᷄ᴑꜝᴠᴒͼꜝꜜͼⱫԜᴦᴠͼ᷇ԓͼⱠ˲ᶐ᷊ԓͼ
Ԝꜜᴑͼ᷈˲᷉ᶐ᷊ͼԜꜜᴑͼᴢᴠ꞉ꜜⱲͼᴡⱳᴒͼⱨⱬ᷄ϷꜝꜙͼϷᴢᴒᴠᴡ꞉ꜝꜜꜜԜ꞉ᴟᴒͼԜᴡͼꜞᴟᴒ᷄ᴑꜝᴠᴒͼꜝꜜͼⱫԜᴦᴠͼ᷇ԓͼ᷉˲ᶐ᷊ԓͼ᷿⅍ᶐ᷊ԓͼ
Ⱡ˲ᶐ᷊ԓ ᷈᷉⅍ᶐ᷊ԓͼ᷿᷈᷾ᶐ᷊ԓͼԜꜜᴑͼ᷈˲᷉ᶐ᷊᷅ͼⱨꜜͼԜᴑᴑ꞉ᴡ꞉ꜝꜜԜꞌͼϷꜝꜙͼԜᴠᴠᴒᴠᴠꜛᴒꜜᴡͼᴤ꞉ꞌꞌͼԝᴒͼᴐꜝꜜᴑᴢᴐᴡᴒᴑͼꜝꜜͼⱫԜᴦͼ᷊᷉˲ᶐ᷊ͼ
ⱱꜝᴟᴠᴢԝ꞊ᴒᴐᴡᴠͼꜜꜝᴡͼᴒꜜᴡᴒᴟ꞉ꜜⱲͼ꜡ꜙⱬ᷅ͼ
9.12
Statistical/Analytic Issues
9.12.1 Adjustment for Covariates
ᴁⱳᴒͼԜꜜԜꞌᴦᴠ꞉ᴠͼꜝⱱͼᴡⱳᴒͼꜞᴟ꞉ꜛԜᴟᴦͼԜꜜᴑͼᴠᴒᴐꜝꜜᴑԜᴟᴦͼᴒⱱⱱ꞉ᴐԜᴐᴦͼԜᴑ꞊ᴢᴠᴡᴠͼⱱꜝᴟͼᴡⱳᴒͼꜜꜝᴟꜛԜꞌ꞉ᴧᴒᴑͼԝԜᴠᴒꞌ꞉ꜜᴒͼⱶⱨⱬͼ
ԜᴡᴡԜᴐꞋͼᴟԜᴡᴒ᷅ͼ꜠ꜝͼԜᴑᴑ꞉ᴡ꞉ꜝꜜԜꞌͼᴐꜝᴣԜᴟ꞉ԜᴡᴒͼԜᴑ꞊ᴢᴠᴡꜛᴒꜜᴡͼ꞉ᴠͼꜞꞌԜꜜꜜᴒᴑ᷅
9.12.2 Handling of Dropouts or Missing Data
ⱨꞌꞌͼԜᴣԜ꞉ꞌԜԝꞌᴒͼᴑԜᴡԜͼᴤ꞉ꞌꞌͼԝᴒͼ꞉ꜜᴐꞌᴢᴑᴒᴑͼ꞉ꜜͼᴡⱳᴒͼԜꜜԜꞌᴦᴠ꞉ᴠ᷅ͼᴁⱳᴒͼꞌᴒꜜⱲᴡⱳͼꜝⱱͼᴡ꞉ꜛᴒͼԜͼᴠᴢԝ꞊ᴒᴐᴡͼᴤԜᴠͼꜝԝᴠᴒᴟᴣᴒᴑͼ
ᴑᴢᴟ꞉ꜜⱲͼᴡⱳᴒͼᴒⱱⱱ꞉ᴐԜᴐᴦͼᴒᴣԜꞌᴢԜᴡ꞉ꜝꜜͼꜞᴒᴟ꞉ꜝᴑͼᴤ꞉ꞌꞌͼԝᴒͼ꞉ꜜᴐꞌᴢᴑᴒᴑͼԜᴠͼԜͼᴣԜᴟ꞉Ԝԝꞌᴒͼ꞉ꜜͼᴡⱳᴒͼⱲᴒꜜᴒᴟԜꞌ꞉ᴧᴒᴑͼꞌ꞉ꜜᴒԜᴟͼ
ꜛꜝᴑᴒꞌͼᴡꜝͼԜᴑ꞊ᴢᴠᴡͼⱱꜝᴟͼᴑ꞉ⱱⱱᴒᴟᴒꜜᴐᴒᴠͼ꞉ꜜͼⱱꜝꞌꞌꜝᴤ᷄ᴢꜞͼᴡ꞉ꜛᴒ᷅
9.12.3 Interim Analysis and Data Monitoring
꜠ꜝͼ꞉ꜜᴡᴒᴟ꞉ꜛͼԜꜜԜꞌᴦᴠᴒᴠͼԜᴟᴒͼꜞꞌԜꜜꜜᴒᴑ᷅ͼⱶꜝᴤᴒᴣᴒᴟԓͼԜꜜͼ꞉ꜜᴑᴒꜞᴒꜜᴑᴒꜜᴡͼⱫᴀꜚⱩͼᴤ꞉ꞌꞌͼԝᴒͼᴒᴠᴡԜԝꞌ꞉ᴠⱳᴒᴑͼᴡꜝͼꜞᴟꜝᴣ꞉ᴑᴒͼ
ꜝꜜⱲꜝ꞉ꜜⱲԓͼ꞉ꜜᴑᴒꜞᴒꜜᴑᴒꜜᴡͼᴟᴒᴣ꞉ᴒᴤͼԜꜜᴑͼԜᴠᴠᴒᴠᴠꜛᴒꜜᴡͼꜝⱱͼᴡⱳᴒͼᴠԜⱱᴒᴡᴦͼᴑԜᴡԜԓͼԜꜜᴑͼᴡꜝͼᴠԜⱱᴒⱲᴢԜᴟᴑͼᴡⱳᴒͼ꞉ꜜᴡᴒᴟᴒᴠᴡᴠͼԜꜜᴑͼ
ᴠԜⱱᴒᴡᴦͼꜝⱱͼᴡⱳᴒͼꜞԜᴟᴡ꞉ᴐ꞉ꜞԜᴡ꞉ꜜⱲͼᴠᴢԝ꞊ᴒᴐᴡᴠͼ꞉ꜜͼᴡⱳᴒͼᴠᴡᴢᴑᴦ᷅ͼⱨꜜԜꞌᴦᴠ꞉ᴠͼꜝⱱͼᴡⱳᴒͼᴑԜᴡԜͼⱱꜝᴟͼⱫᴀꜚⱩͼᴟᴒᴣ꞉ᴒᴤͼᴤ꞉ꞌꞌͼԝᴒͼ
ᴐꜝꜜᴑᴢᴐᴡᴒᴑͼԜᴐᴐꜝᴟᴑ꞉ꜜⱲͼᴡꜝͼᴡⱳᴒͼⱫᴀꜚⱩͼⱪⱳԜᴟᴡᴒᴟͼԜꜜᴑͼⱫᴀꜚⱩͼᴀⱨ᷅͟ͼⱩᴒᴐԜᴢᴠᴒͼꜜꜝͼⱱꜝᴟꜛԜꞌͼⱳᴦꜞꜝᴡⱳᴒᴠ꞉ᴠͼ
ᴡᴒᴠᴡ꞉ꜜⱲͼⱱꜝᴟͼᴠԜⱱᴒᴡᴦͼԜᴠᴠᴒᴠᴠꜛᴒꜜᴡᴠͼ꞉ᴠͼꜞꞌԜꜜꜜᴒᴑԓͼꜛᴢꞌᴡ꞉ꜞꞌ꞉ᴐ꞉ᴡᴦͼᴐꜝꜜᴐᴒᴟꜜᴠͼᴟᴒⱲԜᴟᴑ꞉ꜜⱲͼᴟᴒꜞᴒԜᴡᴒᴑͼԜꜜԜꞌᴦᴠᴒᴠͼԜᴟᴒͼ
ꜜꜝᴡͼԜꜜͼ꞉ᴠᴠᴢᴒ᷅
9.12.4 Multicenter Studies
ⱫԜᴡԜͼⱱᴟꜝꜛͼԜꞌꞌͼᴠᴡᴢᴑᴦͼᴠ꞉ᴡᴒᴠͼᴡⱳԜᴡͼꜞԜᴟᴡ꞉ᴐ꞉ꜞԜᴡᴒͼ꞉ꜜͼᴡⱳ꞉ᴠͼꜞᴟꜝᴡꜝᴐꜝꞌͼᴤ꞉ꞌꞌͼԝᴒͼᴐꜝꜛԝ꞉ꜜᴒᴑͼᴠꜝͼᴡⱳԜᴡͼԜꜜͼԜᴑᴒꜟᴢԜᴡᴒͼ
ꜜᴢꜛԝᴒᴟͼꜝⱱͼᴠᴢԝ꞊ᴒᴐᴡᴠͼᴤ꞉ꞌꞌͼԝᴒͼԜᴣԜ꞉ꞌԜԝꞌᴒͼⱱꜝᴟͼԜꜜԜꞌᴦᴠ꞉ᴠ᷅
9.12.5 Multiple Comparisons/Multiplicity
ᴁⱳᴒͼⱲꞌꜝԝԜꞌͼⱱԜꜛ꞉ꞌᴦ᷄ᴤ꞉ᴠᴒͼᴁᴦꜞᴒͼⱷͼᴒᴟᴟꜝᴟͼᴟԜᴡᴒͼӿⱴᴄⱬϸԐͼⱱꜝᴟͼᴡⱳᴒͼᴠᴡԜᴡ꞉ᴠᴡ꞉ᴐԜꞌͼᴡᴒᴠᴡᴠͼꜝⱱͼᴡⱳᴒͼꜞᴟ꞉ꜛԜᴟᴦͼԜꜜᴑͼᴟԜꜜꞋͼ
ꜝᴟᴑᴒᴟᴒᴑͼᴠᴒᴐꜝꜜᴑԜᴟᴦͼᴒⱱⱱ꞉ᴐԜᴐᴦͼᴒꜜᴑꜞꜝ꞉ꜜᴡᴠͼӿᴟԜꜜꞋͼᴠꜞᴒᴐ꞉ⱱ꞉ᴒᴑͼ꞉ꜜͼᴀᴒᴐᴡ꞉ꜝꜜͼ⅍᷅᷾᷅᷈Ԑͼᴤ꞉ꞌꞌͼԝᴒͼᴐꜝꜜᴡᴟꜝꞌꞌᴒᴑͼԜᴡͼ᷿᷇᷅᷇᷅ͼ
ᴁꜝͼᴠᴡᴟꜝꜜⱲꞌᴦͼᴐꜝꜜᴡᴟꜝꞌͼᴡⱳᴒͼⱲꞌꜝԝԜꞌͼⱴᴄⱬϸͼԜᴡͼᴡⱳ꞉ᴠͼꞌᴒᴣᴒꞌԓͼԜͼⱲᴒꜜᴒᴟԜꞌͼⱲԜᴡᴒꞋᴒᴒꜞ꞉ꜜⱲͼԜꜞꜞᴟꜝԜᴐⱳͼᴤ꞉ᴡⱳͼԝᴟԜꜜᴐⱳᴒᴠͼ
ⱱꜝᴟͼᴒԜᴐⱳͼԜᴐᴡ꞉ᴣᴒͼᴡᴟᴒԜᴡꜛᴒꜜᴡͼⱲᴟꜝᴢꜞͼᴡꜝͼꜞꞌԜᴐᴒԝꜝͼⱲᴟꜝᴢꜞͼᴐꜝꜛꜞԜᴟ꞉ᴠꜝꜜͼᴤ꞉ꞌꞌͼԝᴒͼᴢᴡ꞉ꞌ꞉ᴧᴒᴑͼ꞉ꜜͼᴤⱳ꞉ᴐⱳͼᴒԜᴐⱳͼ
ⱱԜꜛ꞉ꞌᴦͼꜝⱱͼᴠᴡԜᴡ꞉ᴠᴡ꞉ᴐԜꞌͼᴡᴒᴠᴡᴠͼᴤ꞉ꞌꞌͼԝᴒͼᴐꜝꜜᴑᴢᴐᴡᴒᴑͼ꞉ꜜͼԜͼᴠᴒꜟᴢᴒꜜᴡ꞉ԜꞌͼꜛԜꜜꜜᴒᴟ᷅ͼᴀꜞᴒᴐ꞉ⱱ꞉ᴐԜꞌꞌᴦԓͼԜͼᴡⱳᴟᴒᴒ᷄ԝᴟԜꜜᴐⱳͼ
ⱲᴒꜜᴒᴟԜꞌͼⱲԜᴡᴒꞋᴒᴒꜞ꞉ꜜⱲͼꜞᴟꜝᴐᴒᴑᴢᴟᴒᴤ꞉ᴡⱳͼⱱꜝᴢᴟͼⱱԜꜛ꞉ꞌ꞉ᴒᴠͼꜝⱱͼⱳᴦꜞꜝᴡⱳᴒᴠᴒᴠͼᴤ꞉ꞌꞌͼԝᴒͼᴑᴒⱱ꞉ꜜᴒᴑͼԜᴠͼⱱꜝꞌꞌꜝᴤᴠⱡ

Ⱬᴅ᷄᷉Ⱡ᷊᷇
ⱪꞌ꞉ꜜ꞉ᴐԜꞌͼᴁᴟ꞉Ԝꞌͼ͟ᴟꜝᴡꜝᴐꜝꞌⱡͼⱫᴅ᷄᷉Ⱡ᷊᷊᷇᷄᷇
ⱨꜛᴒꜜᴑꜛᴒꜜᴡͼ᷊᷅᷇ͼⱴ꞉ꜜԜꞌⱡͼ᷇ⱠͼꜗԜꜜᴢԜᴟᴦ᷉᷇᷈ⅎ
ⱪꜝꜜⱱ꞉ᴑᴒꜜᴡ꞉Ԝꞌ
͟ԜⱲᴒͼ˲᷾
ⱫᴦԜᴥͼⱪꜝᴟꜞ᷅

ⱴԜꜛ꞉ꞌᴦͼ᷈ͼӿⱴ᷈Ԑⱡͼⱶᴦꜞꜝᴡⱳᴒᴠ꞉ᴠͼᴡᴒᴠᴡᴠͼⱱꜝᴟͼᴡⱳᴒͼꜞᴟ꞉ꜛԜᴟᴦͼᴒⱱⱱ꞉ᴐԜᴐᴦͼᴒꜜᴑꜞꜝ꞉ꜜᴡԓͼꜝꜜᴒͼᴡᴒᴠᴡͼⱱꜝᴟͼᴒԜᴐⱳͼԜᴐᴡ꞉ᴣᴒͼ
ᴡᴟᴒԜᴡꜛᴒꜜᴡͼᴡꜝͼꜞꞌԜᴐᴒԝꜝͼᴐꜝꜛꜞԜᴟ꞉ᴠꜝꜜͼꜝᴟᴑᴒᴟᴒᴑͼԝᴦͼⱳ꞉ⱲⱳᴒᴠᴡͼᴡꜝᴡԜꞌͼꜛꜝꜜᴡⱳꞌᴦͼᴑꜝᴠᴒӿⱶ᷈᷈ԓͼⱶ᷈᷉ԓͼԜꜜᴑͼⱶ᷊᷈Ԑ᷅

ⱴԜꜛ꞉ꞌᴦͼ᷉ͼӿⱴ᷉Ԑⱡͼⱶᴦꜞꜝᴡⱳᴒᴠ꞉ᴠͼᴡᴒᴠᴡᴠͼⱱꜝᴟͼᴡⱳᴒͼⱱ꞉ᴟᴠᴡͼᴟԜꜜꞋᴒᴑͼᴠᴒᴐꜝꜜᴑԜᴟᴦͼᴒꜜᴑꜞꜝ꞉ꜜᴡԓͼꜝꜜᴒͼᴡᴒᴠᴡͼⱱꜝᴟͼᴒԜᴐⱳͼ
Ԝᴐᴡ꞉ᴣᴒͼᴡᴟᴒԜᴡꜛᴒꜜᴡͼᴡꜝͼꜞꞌԜᴐᴒԝꜝͼᴐꜝꜛꜞԜᴟ꞉ᴠꜝꜜͼꜝᴟᴑᴒᴟᴒᴑͼԝᴦͼⱳ꞉ⱲⱳᴒᴠᴡͼᴡꜝᴡԜꞌͼꜛꜝꜜᴡⱳꞌᴦͼᴑꜝᴠᴒӿⱶ᷉᷈ԓͼⱶ᷉᷉ԓͼԜꜜᴑͼ
ⱶ᷊᷉Ԑ᷅

ⱴԜꜛ꞉ꞌᴦͼ᷊ͼӿⱴ᷊Ԑⱡͼⱶᴦꜞꜝᴡⱳᴒᴠ꞉ᴠͼᴡᴒᴠᴡᴠͼⱱꜝᴟͼᴡⱳᴒͼᴠᴒᴐꜝꜜᴑͼᴟԜꜜꞋᴒᴑͼᴠᴒᴐꜝꜜᴑԜᴟᴦͼᴒꜜᴑꜞꜝ꞉ꜜᴡԓͼꜝꜜᴒͼᴡᴒᴠᴡͼⱱꜝᴟͼᴒԜᴐⱳͼ
Ԝᴐᴡ꞉ᴣᴒͼᴡᴟᴒԜᴡꜛᴒꜜᴡͼᴡꜝͼꜞꞌԜᴐᴒԝꜝͼᴐꜝꜛꜞԜᴟ꞉ᴠꜝꜜͼꜝᴟᴑᴒᴟᴒᴑͼԝᴦͼⱳ꞉ⱲⱳᴒᴠᴡͼᴡꜝᴡԜꞌͼꜛꜝꜜᴡⱳꞌᴦͼᴑꜝᴠᴒӿⱶ᷊᷈ԓͼⱶ᷊᷉ԓͼԜꜜᴑͼ
ⱶ᷊᷊Ԑ᷅

ⱴԜꜛ꞉ꞌᴦͼ᷾ͼӿⱴ᷾Ԑⱡͼⱶᴦꜞꜝᴡⱳᴒᴠ꞉ᴠͼᴡᴒᴠᴡᴠͼⱱꜝᴟͼᴡⱳᴒͼᴡⱳ꞉ᴟᴑͼᴟԜꜜꞋᴒᴑͼᴠᴒᴐꜝꜜᴑԜᴟᴦͼᴒꜜᴑꜞꜝ꞉ꜜᴡԓͼꜝꜜᴒͼᴡᴒᴠᴡͼⱱꜝᴟͼᴒԜᴐⱳͼ
Ԝᴐᴡ꞉ᴣᴒͼᴡᴟᴒԜᴡꜛᴒꜜᴡͼᴡꜝͼꜞꞌԜᴐᴒԝꜝͼᴐꜝꜛꜞԜᴟ꞉ᴠꜝꜜͼꜝᴟᴑᴒᴟᴒᴑͼԝᴦͼⱳ꞉ⱲⱳᴒᴠᴡͼᴡꜝᴡԜꞌͼꜛꜝꜜᴡⱳꞌᴦͼᴑꜝᴠᴒӿⱶ᷾᷈ԓͼⱶ᷾᷉ԓͼԜꜜᴑͼ
ⱶ᷊᷾Ԑ᷅
ᴁⱳᴒͼ᷾ͼᴠᴒᴡᴠͼꜝⱱͼⱳᴦꜞꜝᴡⱳᴒᴠᴒᴠͼ꞉ꜜͼⱴ᷈ԓͼⱴ᷉ԓͼⱴ᷊ԓͼԜꜜᴑͼⱴ᷾ͼᴤ꞉ꞌꞌͼԝᴒͼᴡᴒᴠᴡᴒᴑͼ꞉ꜜͼԜͼⱱ꞉ᴥᴒᴑͼᴠᴒꜟᴢᴒꜜᴐᴒͼᴤ꞉ᴡⱳ꞉ꜜͼᴒԜᴐⱳͼ
Ԝᴐᴡ꞉ᴣᴒͼᴡᴟᴒԜᴡꜛᴒꜜᴡͼⱲᴟꜝᴢꜞͼᴡꜝͼꜞꞌԜᴐᴒԝꜝͼⱲᴟꜝᴢꜞͼᴐꜝꜛꜞԜᴟ꞉ᴠꜝꜜͼꜝᴟͼԝᴟԜꜜᴐⱳ᷅ͼᴁᴒᴠᴡ꞉ꜜⱲͼᴤ꞉ᴡⱳ꞉ꜜͼԜͼԝᴟԜꜜᴐⱳͼᴤ꞉ꞌꞌͼ
ᴐꜝꜜᴡ꞉ꜜᴢᴒͼ꞉ꜜͼᴠᴒꜟᴢᴒꜜᴐᴒͼᴢꜜᴡ꞉ꞌᴡⱳᴒͼⱱ꞉ᴟᴠᴡͼᴡᴒᴠᴡͼᴡⱳԜᴡͼᴡⱳᴒͼꜜᴢꞌꞌͼⱳᴦꜞꜝᴡⱳᴒᴠ꞉ᴠͼᴐԜꜜꜜꜝᴡͼԝᴒͼᴟᴒ꞊ᴒᴐᴡᴒᴑⱢͼᴠᴡԜᴡ꞉ᴠᴡ꞉ᴐԜꞌͼ
ᴠ꞉Ⱳꜜ꞉ⱱ꞉ᴐԜꜜᴐᴒͼᴐԜꜜꜜꜝᴡͼԝᴒͼᴑᴒᴐꞌԜᴟᴒᴑͼⱱꜝᴟͼᴡⱳԜᴡͼᴡᴒᴠᴡͼꜝᴟͼⱱꜝᴟͼԜꜜᴦͼꜝⱱͼᴡⱳᴒͼᴟᴒꜛԜ꞉ꜜ꞉ꜜⱲͼᴡᴒᴠᴡᴠͼᴤ꞉ᴡⱳ꞉ꜜͼᴡⱳᴒͼԝᴟԜꜜᴐⱳ᷅
ᴄ꞉ᴡⱳ꞉ꜜͼԜͼⱱԜꜛ꞉ꞌᴦԓͼⱳᴦꜞꜝᴡⱳᴒᴠᴒᴠͼᴤ꞉ꞌꞌͼԝᴒͼᴡᴒᴠᴡᴒᴑͼᴢᴠ꞉ꜜⱲͼԜͼᴐꜝꜜᴠᴒᴟᴣԜᴡ꞉ᴣᴒͼⱩꜝꜜⱱᴒᴟᴟꜝꜜ꞉᷄ԝԜᴠᴒᴑͼꜞᴟꜝᴐᴒᴑᴢᴟᴒͼᴤ꞉ᴡⱳͼ
ᴒꜟᴢԜꞌͼᴤᴒ꞉ⱲⱳᴡᴠͼⱱꜝᴟͼᴒԜᴐⱳͼᴡᴒᴠᴡͼᴠᴒᴡͼԜᴡͼ᷈᷅⅍ⅎӼͼᴠ꞉Ⱳꜜ꞉ⱱ꞉ᴐԜꜜᴐᴒͼꞌᴒᴣᴒꞌͼӿĮ᷊᷆Ԑ᷅ͼⱷⱱͼᴡⱳᴒͼꜜᴢꞌꞌͼⱳᴦꜞꜝᴡⱳᴒᴠ꞉ᴠͼⱱꜝᴟͼԜͼᴡᴒᴠᴡͼ꞉ᴠͼ
ᴟᴒ꞊ᴒᴐᴡᴒᴑԓͼĮͼᴤ꞉ꞌꞌͼԝᴒͼꜞᴟꜝꜞԜⱲԜᴡᴒᴑͼᴒꜜᴡ꞉ᴟᴒꞌᴦͼᴡꜝͼᴡⱳᴒͼꜜᴒᴥᴡͼᴡᴒᴠᴡͼ꞉ꜜͼᴡⱳᴒͼᴠᴒꜟᴢᴒꜜᴐᴒԓͼᴤⱳ꞉ᴐⱳͼᴤ꞉ꞌꞌͼᴡⱳᴒꜜͼԝᴒͼᴡᴒᴠᴡᴒᴑͼ
Ԝᴡͼᴡⱳᴒͼ᷈᷅⅍ⅎӼͼᴠ꞉Ⱳꜜ꞉ⱱ꞉ᴐԜꜜᴐᴒͼꞌᴒᴣᴒꞌ᷅
ᴁꜝͼⱱᴢᴟᴡⱳᴒᴟͼ꞉ꞌꞌᴢᴠᴡᴟԜᴡᴒͼᴡⱳ꞉ᴠͼԜꜞꜞᴟꜝԜᴐⱳԓͼᴡⱳᴒͼᴡᴒᴠᴡͼⱱꜝᴟͼᴡⱳᴒͼꜞᴟ꞉ꜛԜᴟᴦͼᴒꜜᴑꜞꜝ꞉ꜜᴡͼᴤ꞉ꞌꞌͼԝᴒͼᴐꜝꜜᴑᴢᴐᴡᴒᴑͼⱱ꞉ᴟᴠᴡͼԜᴡͼᴡⱳᴒͼ
᷈᷅⅍ⅎӼͼᴠ꞉Ⱳꜜ꞉ⱱ꞉ᴐԜꜜᴐᴒͼꞌᴒᴣᴒꞌͼⱱꜝᴟͼᴒԜᴐⱳͼԜᴐᴡ꞉ᴣᴒͼᴡᴟᴒԜᴡꜛᴒꜜᴡͼⱲᴟꜝᴢꜞͼᴐꜝꜛꜞԜᴟᴒᴑͼᴤ꞉ᴡⱳͼᴡⱳᴒͼꜞꞌԜᴐᴒԝꜝͼⱲᴟꜝᴢꜞͼԜꜜᴑԓͼ
꞉ⱱͼᴠ꞉Ⱳꜜ꞉ⱱ꞉ᴐԜꜜᴡԓͼᴡⱳᴒͼⱱ꞉ᴟᴠᴡͼᴠᴒᴐꜝꜜᴑԜᴟᴦͼᴒꜜᴑꜞꜝ꞉ꜜᴡͼᴤ꞉ꞌꞌͼԝᴒͼᴠ꞉ꜛ꞉ꞌԜᴟꞌᴦͼᴡᴒᴠᴡᴒᴑͼԜᴡͼᴡⱳᴒͼ᷈᷅⅍ⅎӼͼᴠ꞉Ⱳꜜ꞉ⱱ꞉ᴐԜꜜᴐᴒͼꞌᴒᴣᴒꞌ᷅ͼ
ᴁⱳᴒͼᴡᴒᴠᴡ꞉ꜜⱲͼᴠᴒꜟᴢᴒꜜᴐᴒͼᴤ꞉ꞌꞌͼᴐꜝꜜᴡ꞉ꜜᴢᴒͼ꞉ꜜͼꜝᴟᴑᴒᴟͼᴡⱳᴟꜝᴢⱲⱳͼᴡⱳᴒͼᴟᴒꜛԜ꞉ꜜ꞉ꜜⱲͼᴠᴒᴐꜝꜜᴑԜᴟᴦͼᴒꜜᴑꜞꜝ꞉ꜜᴡᴠͼⱱꜝᴟͼᴒԜᴐⱳͼ
Ԝᴐᴡ꞉ᴣᴒͼᴡᴟᴒԜᴡꜛᴒꜜᴡͼⱲᴟꜝᴢꜞͼᴡꜝͼꜞꞌԜᴐᴒԝꜝͼᴐꜝꜛꜞԜᴟ꞉ᴠꜝꜜͼꜝᴟͼԝᴟԜꜜᴐⱳͼԜᴠͼꞌꜝꜜⱲͼԜᴠͼᴡⱳᴒͼꜜᴢꞌꞌͼⱳᴦꜞꜝᴡⱳᴒᴠ꞉ᴠͼ꞉ᴠͼᴟᴒ꞊ᴒᴐᴡᴒᴑͼ
Ԝᴡͼᴡⱳᴒͼ᷈᷅⅍ⅎӼͼᴠ꞉Ⱳꜜ꞉ⱱ꞉ᴐԜꜜᴐᴒͼꞌᴒᴣᴒꞌ᷅ͼ
ᴁᴒᴠᴡ꞉ꜜⱲͼᴤ꞉ᴡⱳ꞉ꜜͼᴡⱳᴒͼꞌԜᴠᴡͼⱱԜꜛ꞉ꞌᴦͼӿⱴ᷾Ԑͼᴤ꞉ꞌꞌͼᴢᴡ꞉ꞌ꞉ᴧᴒͼᴡⱳᴒͼᴟᴒꜛԜ꞉ꜜ꞉ꜜⱲͼĮͼԝᴦͼԜꜞꜞꞌᴦ꞉ꜜⱲͼᴡⱳᴒⱶꜝꞌꜛ᷄Ⱪꜝꜜⱱᴒᴟᴟꜝꜜ꞉ͼ
ꜞᴟꜝᴐᴒᴑᴢᴟᴒ᷅ͼ
9.12.6 Sensitivity Analyses
ᴀᴒꜜᴠ꞉ᴡ꞉ᴣ꞉ᴡᴦͼԜꜜԜꞌᴦᴠᴒᴠͼᴤ꞉ꞌꞌͼԝᴒͼꜞᴒᴟⱱꜝᴟꜛᴒᴑͼꜝꜜͼᴡⱳᴒͼꜞᴟ꞉ꜛԜᴟᴦͼᴒⱱⱱ꞉ᴐԜᴐᴦͼᴒꜜᴑꜞꜝ꞉ꜜᴡͼᴡꜝͼᴒᴣԜꞌᴢԜᴡᴒͼᴡⱳᴒͼ
ᴟꜝԝᴢᴠᴡꜜᴒᴠᴠͼꜝⱱͼᴡⱳᴒͼᴟᴒᴠᴢꞌᴡᴠͼⱱᴟꜝꜛᴡⱳᴒͼꜞᴟ꞉ꜛԜᴟᴦͼԜꜜԜꞌᴦᴠ꞉ᴠͼꜛᴒᴡⱳꜝᴑ᷅ͼᴁⱳᴒᴠᴒͼԜꜜԜꞌᴦᴠᴒᴠͼᴤ꞉ꞌꞌͼԝᴒͼᴑᴒᴠᴐᴟ꞉ԝᴒᴑͼ꞉ꜜͼ
ᴡⱳᴒͼᴠᴡԜᴡ꞉ᴠᴡ꞉ᴐԜꞌͼԜꜜԜꞌᴦᴠ꞉ᴠͼꜞꞌԜꜜ᷅

Ⱬᴅ᷄᷉Ⱡ᷊᷇
ⱪꞌ꞉ꜜ꞉ᴐԜꞌͼᴁᴟ꞉Ԝꞌͼ͟ᴟꜝᴡꜝᴐꜝꞌⱡͼⱫᴅ᷄᷉Ⱡ᷊᷊᷇᷄᷇
ⱨꜛᴒꜜᴑꜛᴒꜜᴡͼ᷊᷅᷇ͼⱴ꞉ꜜԜꞌⱡͼ᷇ⱠͼꜗԜꜜᴢԜᴟᴦ᷉᷇᷈ⅎ
ⱪꜝꜜⱱ꞉ᴑᴒꜜᴡ꞉Ԝꞌ
͟ԜⱲᴒͼ˲᷿
ⱫᴦԜᴥͼⱪꜝᴟꜞ᷅
10 STUDY ADMINISTRATIVE STRUCTURE
ᴁⱳᴒͼᴠᴡᴢᴑᴦͼԜᴑꜛ꞉ꜜ꞉ᴠᴡᴟԜᴡ꞉ꜝꜜͼᴠᴡᴟᴢᴐᴡᴢᴟᴒͼ꞉ᴠͼꜞᴟꜝᴣ꞉ᴑᴒᴑͼ꞉ꜜͼᴁԜԝꞌᴒ᷊᷅
Table 3.
Study Administrative Structure
Sponsor Contact/Sponsor Medical 
Director:
ꜗᴒꜜꜜ꞉ⱱᴒᴟͼᴀᴐⱳᴟԜꜜᴧԓͼꜚⱫ
ԓͼⱪꞌ꞉ꜜ꞉ᴐԜꞌͼⱫᴒᴣᴒꞌꜝꜞꜛᴒꜜᴡ
᷊᷇᷇ͼᴀⱳ꞉ᴟᴒͼᴄԜᴦԓͼꜙᴒᴥ꞉ꜜⱲᴡꜝꜜԓͼꜚⱨͼ᷇᷉᷾᷉᷈ͼᴂᴀⱨ
͟ⱳꜝꜜᴒⱡͼ
Medical Monitor (US, Canada):
ԓͼꜚⱫ
ԓͼⱪꞌ꞉ꜜ꞉ᴐԜꞌͼⱫᴒᴣᴒꞌꜝꜞꜛᴒꜜᴡ
᷊᷇᷇ͼᴀⱳ꞉ᴟᴒͼᴄԜᴦԓͼꜙᴒᴥ꞉ꜜⱲᴡꜝꜜԓͼꜚⱨͼ᷇᷉᷾᷉᷈ͼᴂᴀⱨ
͟ⱳꜝꜜᴒⱡͼ
ⱬꜛԜ꞉ꞌⱡͼ
Medical Monitor (Jordan, Europe):
ԓͼꜚⱫ
ԓͼⱪꞌ꞉ꜜ꞉ᴐԜꞌͼⱫᴒᴣᴒꞌꜝꜞꜛᴒꜜᴡ
᷊᷇᷇ͼᴀⱳ꞉ᴟᴒͼᴄԜᴦԓͼꜙᴒᴥ꞉ꜜⱲᴡꜝꜜԓͼꜚⱨͼ᷇᷉᷾᷉᷈ͼᴂᴀⱨ
͟ⱳꜝꜜᴒⱡͼ
ⱬꜛԜ꞉ꞌⱡͼ
Study Monitoring (US):
ϸⱳꜝԓͼⱷꜜᴐ᷅
ԓͼ
ԓͼ
͟ⱳꜝꜜᴒⱡͼ
Study Monitoring (Jordan)
ᴁᴟ꞉ᴢꜛꜞⱳԜᴟꜛԜ
ԓͼ
ԓͼ
ԓͼꜗꜝᴟᴑԜꜜ
͟ⱳꜝꜜᴒⱡͼ
Study Monitoring (Canada)
ϸᴒᴑͼꜚԜꜞꞌᴒͼᴁᴟ꞉ԜꞌᴠͼⱷꜜᴐꜝᴟꜞꜝᴟԜᴡᴒᴑ
ԓͼ
ԓͼ
ԓͼⱪԜꜜԜᴑԜԓͼ
͟ⱳꜝꜜᴒⱡͼ
Study Monitoring (Europe)
ⱫᴦԜᴥͼⱪꜝᴟꜞ᷅ԓͼԜꜜͼ꞉ꜜᴑ꞉ᴟᴒᴐᴡԓͼᴤⱳꜝꞌꞌᴦ᷄ꜝᴤꜜᴒᴑͼᴠᴢԝᴠ꞉ᴑ꞉Ԝᴟᴦͼꜝⱱͼ
ᴀⱳ꞉ᴟᴒͼꜞꞌᴐ᷅
᷿᷿ͼ꜠ᴒᴡᴤꜝᴟꞋͼⱫᴟ꞉ᴣᴒԓͼⱩᴢᴟꞌ꞉ꜜⱲᴡꜝꜜԓͼꜚⱨͼ᷇᷈˲᷊᷇
͟ⱳꜝꜜᴒⱡͼ
10.1
Institutional Review Board/Research Ethics Board/Independent 
Ethics Committee
ᴁⱳᴒͼꜞᴟꜝᴡꜝᴐꜝꞌͼԜꜜᴑͼԜꞌꞌͼꜞᴟꜝᴡꜝᴐꜝꞌͼԜꜛᴒꜜᴑꜛᴒꜜᴡᴠͼꜛᴢᴠᴡͼԝᴒͼᴠ꞉ⱲꜜᴒᴑͼԜꜜᴑͼᴑԜᴡᴒᴑͼԝᴦͼᴡⱳᴒͼⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟͼԜꜜᴑͼ
Ԝꜞꜞᴟꜝᴣᴒᴑͼ꞉ꜜͼᴤᴟ꞉ᴡ꞉ꜜⱲͼԝᴦͼᴡⱳᴒͼⱷϸⱩ᷆ϸⱬⱩ᷆ⱷⱬⱪͼ꞉ꜜͼԜᴐᴐꜝᴟᴑԜꜜᴐᴒͼᴤ꞉ᴡⱳͼⱵⱪ͟ͼꜞᴟ꞉ꜝᴟͼᴡꜝͼ꞉ꜛꜞꞌᴒꜛᴒꜜᴡԜᴡ꞉ꜝꜜ᷅ͼⱷꜜͼ
Ԝᴑᴑ꞉ᴡ꞉ꜝꜜԓͼᴡⱳᴒͼⱷϸⱩ᷆ϸⱬⱩ᷆ⱷⱬⱪͼꜛᴢᴠᴡͼԜꜞꜞᴟꜝᴣᴒͼᴡⱳᴒͼᴤᴟ꞉ᴡᴡᴒꜜͼ꞉ꜜⱱꜝᴟꜛᴒᴑͼᴐꜝꜜᴠᴒꜜᴡͼԜꜜᴑͼԜᴠᴠᴒꜜᴡͼⱱꜝᴟꜛᴠԓͼԜꜜᴦͼ
ᴐꜝꜜᴠᴒꜜᴡͼꜝᴟͼԜᴠᴠᴒꜜᴡͼⱱꜝᴟꜛͼᴢꜞᴑԜᴡᴒᴠԓͼᴠᴢԝ꞊ᴒᴐᴡͼᴟᴒᴐᴟᴢ꞉ᴡꜛᴒꜜᴡͼꜞᴟꜝᴐᴒᴑᴢᴟᴒᴠͼӿᴒ᷅Ⱳ᷅ԓͼԜᴑᴣᴒᴟᴡ꞉ᴠᴒꜛᴒꜜᴡᴠԐԓͼԜꜜᴑͼԜꜜᴦͼ
ᴤᴟ꞉ᴡᴡᴒꜜͼ꞉ꜜⱱꜝᴟꜛԜᴡ꞉ꜝꜜͼᴡꜝͼԝᴒͼꜞᴟꜝᴣ꞉ᴑᴒᴑͼᴡꜝͼᴠᴢԝ꞊ᴒᴐᴡᴠͼꜞᴟ꞉ꜝᴟͼᴡꜝͼ꞉ꜛꜞꞌᴒꜛᴒꜜᴡԜᴡ꞉ꜝꜜ᷅ͼᴁⱳᴒͼⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟͼꜛᴢᴠᴡͼ
ꜞᴟꜝᴣ꞉ᴑᴒͼԜꜜͼԜꜜꜜᴢԜꞌͼᴟᴒꜞꜝᴟᴡͼᴡꜝͼᴡⱳᴒͼⱷϸⱩ᷆ϸⱬⱩ᷆ⱷⱬⱪͼꜝꜜͼᴡⱳᴒͼꜞᴟꜝⱲᴟᴒᴠᴠͼꜝⱱͼᴡⱳᴒͼᴠᴡᴢᴑᴦͼ꞉ꜜᴐꞌᴢᴑ꞉ꜜⱲͼꜜᴢꜛԝᴒᴟͼꜝⱱͼ
ᴠᴢԝ꞊ᴒᴐᴡᴠͼᴒꜜᴟꜝꞌꞌᴒᴑԓͼᴑ꞉ᴠᴐꜝꜜᴡ꞉ꜜᴢᴒᴑԓͼԜꜜᴑͼᴀⱨⱬᴠ᷅ͼⱷᴡͼ꞉ᴠͼᴟᴒꜟᴢ꞉ᴟᴒᴑͼᴡⱳԜᴡͼԜͼᴦᴒԜᴟꞌᴦͼᴟᴒᴣ꞉ᴒᴤͼꜝⱱͼᴡⱳᴒͼꜞᴟꜝᴡꜝᴐꜝꞌͼԝᴦͼ
ᴡⱳᴒͼⱷϸⱩ᷆ϸⱬⱩ᷆ⱷⱬⱪͼԝᴒͼᴑꜝᴐᴢꜛᴒꜜᴡᴒᴑͼ꞉ꜜͼԜͼꞌᴒᴡᴡᴒᴟͼⱱᴟꜝꜛͼᴡⱳᴒͼⱷϸⱩ᷆ϸⱬⱩ᷆ⱷⱬⱪ᷅ͼᴁⱳᴒͼⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟͼꜛᴢᴠᴡͼ
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD

Ⱬᴅ᷄᷉Ⱡ᷊᷇
ⱪꞌ꞉ꜜ꞉ᴐԜꞌͼᴁᴟ꞉Ԝꞌͼ͟ᴟꜝᴡꜝᴐꜝꞌⱡͼⱫᴅ᷄᷉Ⱡ᷊᷊᷇᷄᷇
ⱨꜛᴒꜜᴑꜛᴒꜜᴡͼ᷊᷅᷇ͼⱴ꞉ꜜԜꞌⱡͼ᷇ⱠͼꜗԜꜜᴢԜᴟᴦ᷉᷇᷈ⅎ
ⱪꜝꜜⱱ꞉ᴑᴒꜜᴡ꞉Ԝꞌ
͟ԜⱲᴒͼ˲⅍
ⱫᴦԜᴥͼⱪꜝᴟꜞ᷅
ꜞᴟꜝᴣ꞉ᴑᴒͼꜜꜝᴡ꞉ⱱ꞉ᴐԜᴡ꞉ꜝꜜͼᴡꜝͼᴡⱳᴒͼⱷϸⱩ᷆ϸⱬⱩ᷆ⱷⱬⱪͼꜝⱱͼᴡⱳᴒͼᴐꜝꜛꜞꞌᴒᴡ꞉ꜝꜜԓͼᴡᴒᴟꜛ꞉ꜜԜᴡ꞉ꜝꜜͼꜝᴟͼᴑ꞉ᴠᴐꜝꜜᴡ꞉ꜜᴢԜᴡ꞉ꜝꜜͼꜝⱱͼᴡⱳᴒͼ
ᴠᴡᴢᴑᴦ᷅
10.2
Ethical Conduct of the Study
ᴁⱳᴒͼꜞᴟꜝᴐᴒᴑᴢᴟᴒᴠͼᴠᴒᴡͼꜝᴢᴡͼ꞉ꜜͼᴡⱳ꞉ᴠͼᴐꞌ꞉ꜜ꞉ᴐԜꞌͼᴠᴡᴢᴑᴦͼꜞᴟꜝᴡꜝᴐꜝꞌͼԜᴟᴒͼᴑᴒᴠ꞉ⱲꜜᴒᴑͼᴡꜝͼᴒꜜᴠᴢᴟᴒͼᴡⱳԜᴡͼᴡⱳᴒͼᴀꜞꜝꜜᴠꜝᴟͼԜꜜᴑͼ
ᴡⱳᴒͼⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟͼԜԝ꞉ᴑᴒͼԝᴦͼᴡⱳᴒͼꜞᴟ꞉ꜜᴐ꞉ꜞꞌᴒᴠͼꜝⱱͼᴡⱳᴒͼⱷꜜᴡᴒᴟꜜԜᴡ꞉ꜝꜜԜꞌͼⱪꜝꜜⱱᴒᴟᴒꜜᴐᴒͼꜝꜜͼⱶԜᴟꜛꜝꜜ꞉ᴠԜᴡ꞉ꜝꜜͼӿⱷⱪⱶԐͼ
Ⱳᴢ꞉ᴑᴒꞌ꞉ꜜᴒᴠͼꜝꜜͼⱵⱪ͟ԓͼԜꜞꜞꞌ꞉ᴐԜԝꞌᴒͼꞌꜝᴐԜꞌͼᴟᴒⱲᴢꞌԜᴡꜝᴟᴦͼᴟᴒꜟᴢ꞉ᴟᴒꜛᴒꜜᴡᴠԓͼԜꜜᴑͼᴡⱳᴒͼⱫᴒᴐꞌԜᴟԜᴡ꞉ꜝꜜͼꜝⱱͼⱶᴒꞌᴠ꞉ꜜꞋ꞉ͼ
ӿᴃᴒᴟᴠ꞉ꜝꜜͼ᷉᷇᷇˲Ԑ᷅ͼᴁⱳᴒͼᴐꞌ꞉ꜜ꞉ᴐԜꞌͼᴠᴡᴢᴑᴦͼԜꞌᴠꜝͼᴤ꞉ꞌꞌͼԝᴒͼᴐԜᴟᴟ꞉ᴒᴑͼꜝᴢᴡͼ꞉ꜜͼꞋᴒᴒꜞ꞉ꜜⱲͼᴤ꞉ᴡⱳͼꜜԜᴡ꞉ꜝꜜԜꞌͼԜꜜᴑͼꞌꜝᴐԜꞌͼ
ꞌᴒⱲԜꞌͼᴟᴒꜟᴢ꞉ᴟᴒꜛᴒꜜᴡᴠͼᴈ꞉ꜜͼԜᴐᴐꜝᴟᴑԜꜜᴐᴒͼᴤ꞉ᴡⱳͼᴂꜜ꞉ᴡᴒᴑͼᴀᴡԜᴡᴒᴠͼⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡ꞉ꜝꜜԜꞌͼ꜠ᴒᴤͼⱫᴟᴢⱲͼӿⱷ꜠ⱫԐͼ
ᴟᴒⱲᴢꞌԜᴡ꞉ꜝꜜᴠͼӿ᷉᷈ͼⱪⱴϸͼ᷿⅍Ԑᴊ᷅
10.3
Subject Information and Consent
ⱩᴒⱱꜝᴟᴒͼᴒԜᴐⱳͼᴠᴢԝ꞊ᴒᴐᴡͼ꞉ᴠͼᴒꜜᴟꜝꞌꞌᴒᴑͼ꞉ꜜͼᴡⱳᴒͼᴐꞌ꞉ꜜ꞉ᴐԜꞌͼᴠᴡᴢᴑᴦԓͼᴤᴟ꞉ᴡᴡᴒꜜͼ꞉ꜜⱱꜝᴟꜛᴒᴑͼᴐꜝꜜᴠᴒꜜᴡͼᴤ꞉ꞌꞌͼԝᴒͼꜝԝᴡԜ꞉ꜜᴒᴑͼ
Ԝᴐᴐꜝᴟᴑ꞉ꜜⱲͼᴡꜝͼᴡⱳᴒͼᴟᴒⱲᴢꞌԜᴡꜝᴟᴦͼԜꜜᴑͼꞌᴒⱲԜꞌͼᴟᴒꜟᴢ꞉ᴟᴒꜛᴒꜜᴡᴠͼꜝⱱͼᴡⱳᴒͼꜞԜᴟᴡ꞉ᴐ꞉ꜞԜᴡ꞉ꜜⱲͼᴐꜝᴢꜜᴡᴟᴦ᷅ͼⱨᴠͼꜞԜᴟᴡͼꜝⱱͼᴡⱳ꞉ᴠͼ
ꜞᴟꜝᴐᴒᴑᴢᴟᴒԓͼᴡⱳᴒͼⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟͼꜛᴢᴠᴡͼᴒᴥꜞꞌԜ꞉ꜜͼꜝᴟԜꞌꞌᴦͼԜꜜᴑͼ꞉ꜜͼᴤᴟ꞉ᴡ꞉ꜜⱲͼᴡⱳᴒͼꜜԜᴡᴢᴟᴒԓͼᴑᴢᴟԜᴡ꞉ꜝꜜԓͼԜꜜᴑͼꜞᴢᴟꜞꜝᴠᴒͼ
ꜝⱱͼᴡⱳᴒͼᴠᴡᴢᴑᴦԓͼԜꜜᴑͼᴡⱳᴒͼԜᴐᴡ꞉ꜝꜜͼꜝⱱͼᴡⱳᴒͼᴑᴟᴢⱲͼ꞉ꜜͼᴠᴢᴐⱳͼԜͼꜛԜꜜꜜᴒᴟͼᴡⱳԜᴡͼᴡⱳᴒͼᴠᴡᴢᴑᴦͼᴠᴢԝ꞊ᴒᴐᴡͼ꞉ᴠͼԜᴤԜᴟᴒͼꜝⱱͼᴡⱳᴒͼ
ꜞꜝᴡᴒꜜᴡ꞉Ԝꞌͼᴟ꞉ᴠꞋᴠԓͼ꞉ꜜᴐꜝꜜᴣᴒꜜ꞉ᴒꜜᴐᴒᴠԓͼꜝᴟͼⱨⱬᴠͼᴡⱳԜᴡͼꜛԜᴦͼꜝᴐᴐᴢᴟ᷅ͼᴁⱳᴒͼᴠᴡᴢᴑᴦͼᴠᴢԝ꞊ᴒᴐᴡͼᴠⱳꜝᴢꞌᴑͼԝᴒͼ꞉ꜜⱱꜝᴟꜛᴒᴑͼ
ᴡⱳԜᴡͼⱳᴒ᷆ᴠⱳᴒͼ꞉ᴠͼⱱᴟᴒᴒͼᴡꜝͼᴤ꞉ᴡⱳᴑᴟԜᴤͼⱱᴟꜝꜛͼᴡⱳᴒͼᴠᴡᴢᴑᴦͼԜᴡͼԜꜜᴦͼᴡ꞉ꜛᴒ᷅ͼⱶᴒ᷆ᴠⱳᴒͼᴤ꞉ꞌꞌͼᴟᴒᴐᴒ꞉ᴣᴒͼԜꞌꞌͼ꞉ꜜⱱꜝᴟꜛԜᴡ꞉ꜝꜜͼ
ᴡⱳԜᴡͼ꞉ᴠͼᴟᴒꜟᴢ꞉ᴟᴒᴑͼԝᴦͼⱱᴒᴑᴒᴟԜꞌͼᴟᴒⱲᴢꞌԜᴡ꞉ꜝꜜᴠͼԜꜜᴑͼⱷⱪⱶͼⱲᴢ꞉ᴑᴒꞌ꞉ꜜᴒᴠ᷅ͼᴀᴢԝ꞊ᴒᴐᴡᴠͼᴤⱳꜝͼԜᴟᴒͼᴢꜜᴑᴒᴟͼᴡⱳᴒͼԜⱲᴒͼꜝⱱͼ᷈˲ͼ
ӿꜝᴟͼꞌꜝᴤᴒᴟͼ꞉ⱱͼԜⱲᴒͼꜝⱱͼᴐꜝꜜᴠᴒꜜᴡͼ꞉ᴠͼꞌᴒᴠᴠͼᴡⱳԜꜜͼ᷈˲ͼ꞉ꜜͼԜͼᴠꜞᴒᴐ꞉ⱱ꞉ᴐͼᴐꜝᴢꜜᴡᴟᴦԐͼԜꜜᴑͼᴤⱳꜝᴠᴒͼꞌᴒⱲԜꞌͼⱲᴢԜᴟᴑ꞉Ԝꜜͼꜝᴟͼ
ᴐԜᴟᴒᴡԜꞋᴒᴟͼⱳԜᴠͼꜞᴟꜝᴣ꞉ᴑᴒᴑͼᴤᴟ꞉ᴡᴡᴒꜜͼ꞉ꜜⱱꜝᴟꜛᴒᴑͼᴐꜝꜜᴠᴒꜜᴡͼᴤ꞉ꞌꞌͼꜞᴟꜝᴣ꞉ᴑᴒͼᴡⱳᴒ꞉ᴟͼԜᴠᴠᴒꜜᴡͼᴡꜝͼꜞԜᴟᴡ꞉ᴐ꞉ꜞԜᴡᴒ᷅ͼᴁⱳᴒͼ
ⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟͼꜝᴟͼᴑᴒᴠ꞉Ⱳꜜᴒᴒͼᴤ꞉ꞌꞌͼꜞᴟꜝᴣ꞉ᴑᴒͼᴡⱳᴒͼᴀꜞꜝꜜᴠꜝᴟͼᴤ꞉ᴡⱳͼԜͼᴐꜝꜞᴦͼꜝⱱͼᴡⱳᴒͼⱷϸⱩ᷆ϸⱬⱩ᷆ⱷⱬⱪ᷄Ԝꜞꜞᴟꜝᴣᴒᴑͼ
꞉ꜜⱱꜝᴟꜛᴒᴑͼᴐꜝꜜᴠᴒꜜᴡͼԜꜜᴑͼԜᴠᴠᴒꜜᴡͼⱱꜝᴟꜛᴠͼꜞᴟ꞉ꜝᴟͼᴡꜝͼᴡⱳᴒͼᴠᴡԜᴟᴡͼꜝⱱͼᴡⱳᴒͼᴠᴡᴢᴑᴦ᷅
10.4
Subject Confidentiality
ᴁⱳᴒͼԜꜜꜝꜜᴦꜛ꞉ᴡᴦͼꜝⱱͼꜞԜᴟᴡ꞉ᴐ꞉ꜞԜᴡ꞉ꜜⱲͼᴠᴢԝ꞊ᴒᴐᴡᴠͼꜛᴢᴠᴡͼԝᴒͼꜛԜ꞉ꜜᴡԜ꞉ꜜᴒᴑ᷅ͼᴀᴢԝ꞊ᴒᴐᴡᴠͼᴤ꞉ꞌꞌͼԝᴒͼᴠꜞᴒᴐ꞉ⱱ꞉ᴒᴑͼꜝꜜͼᴠᴡᴢᴑᴦͼ
ᴑꜝᴐᴢꜛᴒꜜᴡᴠͼԝᴦͼᴡⱳᴒ꞉ᴟͼᴠᴢԝ꞊ᴒᴐᴡꜜᴢꜛԝᴒᴟͼԜꜜᴑͼԝ꞉ᴟᴡⱳͼᴑԜᴡᴒͼӿ꞉ⱱͼԜꞌꞌꜝᴤᴒᴑͼԝԜᴠᴒᴑͼꜝꜜͼꞌꜝᴐԜꞌͼᴑԜᴡԜͼꜞᴟꜝᴡᴒᴐᴡ꞉ꜝꜜͼ
ᴟᴒⱲᴢꞌԜᴡ꞉ꜝꜜᴠԐԓͼꜜꜝᴡͼԝᴦͼꜜԜꜛᴒ᷅ͼⱫꜝᴐᴢꜛᴒꜜᴡᴠͼᴡⱳԜᴡͼ꞉ᴑᴒꜜᴡ꞉ⱱᴦͼᴡⱳᴒͼᴠᴢԝ꞊ᴒᴐᴡͼӿᴒ᷅Ⱳ᷅ԓͼᴡⱳᴒͼᴠ꞉Ⱳꜜᴒᴑͼ꞉ꜜⱱꜝᴟꜛᴒᴑͼᴐꜝꜜᴠᴒꜜᴡͼ
ᴑꜝᴐᴢꜛᴒꜜᴡԐͼꜛᴢᴠᴡͼԝᴒͼꜛԜ꞉ꜜᴡԜ꞉ꜜᴒᴑͼ꞉ꜜͼᴐꜝꜜⱱ꞉ᴑᴒꜜᴐᴒͼԝᴦͼᴡⱳᴒͼⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟ᷅
ᴁⱳᴒͼⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟͼԜⱲᴟᴒᴒᴠͼꜜꜝᴡͼᴡꜝͼᴢᴠᴒͼꜝᴟͼᴑ꞉ᴠᴐꞌꜝᴠᴒͼꜞᴟꜝᴡᴒᴐᴡᴒᴑͼⱳᴒԜꞌᴡⱳͼ꞉ꜜⱱꜝᴟꜛԜᴡ꞉ꜝꜜͼꜝᴡⱳᴒᴟͼᴡⱳԜꜜͼԜᴠͼ
ꜞᴒᴟꜛ꞉ᴡᴡᴒᴑͼꜝᴟͼᴟᴒꜟᴢ꞉ᴟᴒᴑͼԝᴦͼᴡⱳᴒͼᴠᴢԝ꞊ᴒᴐᴡͼԜᴢᴡⱳꜝᴟ꞉ᴧԜᴡ꞉ꜝꜜͼꜝᴟͼԜᴠͼᴟᴒꜟᴢ꞉ᴟᴒᴑͼԝᴦͼꞌԜᴤ᷅
10.5
Study Monitoring
ᴁⱳᴒͼᴀꜞꜝꜜᴠꜝᴟͼӿꜝᴟͼᴑᴒᴠ꞉ⱲꜜᴒᴒԐͼᴤ꞉ꞌꞌͼᴐꜝꜜᴑᴢᴐᴡͼԜͼᴠᴡᴢᴑᴦͼ꞉ꜜ꞉ᴡ꞉Ԝᴡ꞉ꜝꜜͼᴣ꞉ᴠ꞉ᴡͼᴡꜝͼᴣᴒᴟ꞉ⱱᴦͼᴡⱳᴒͼꜟᴢԜꞌ꞉ⱱ꞉ᴐԜᴡ꞉ꜝꜜᴠͼꜝⱱͼᴡⱳᴒͼ
ⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟԓͼ꞉ꜜᴠꜞᴒᴐᴡͼᴡⱳᴒͼⱱԜᴐ꞉ꞌ꞉ᴡ꞉ᴒᴠԓͼԜꜜᴑͼ꞉ꜜⱱꜝᴟꜛͼᴡⱳᴒͼⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟͼꜝⱱͼᴟᴒᴠꜞꜝꜜᴠ꞉ԝ꞉ꞌ꞉ᴡ꞉ᴒᴠͼԜꜜᴑͼꜞᴟꜝᴐᴒᴑᴢᴟᴒᴠͼ
ⱱꜝᴟͼᴒꜜᴠᴢᴟ꞉ꜜⱲͼԜᴑᴒꜟᴢԜᴡᴒͼԜꜜᴑͼᴐꜝᴟᴟᴒᴐᴡͼᴑꜝᴐᴢꜛᴒꜜᴡԜᴡ꞉ꜝꜜ᷅
ᴁⱳᴒͼⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟͼꜛᴢᴠᴡͼꜞᴟᴒꜞԜᴟᴒͼԜꜜᴑͼꜛԜ꞉ꜜᴡԜ꞉ꜜͼԜᴑᴒꜟᴢԜᴡᴒͼԜꜜᴑͼԜᴐᴐᴢᴟԜᴡᴒͼᴟᴒᴐꜝᴟᴑᴠͼꜝⱱͼԜꞌꞌͼꜝԝᴠᴒᴟᴣԜᴡ꞉ꜝꜜᴠͼ
ԜꜜᴑͼꜝᴡⱳᴒᴟͼᴑԜᴡԜͼꜞᴒᴟᴡ꞉ꜜᴒꜜᴡͼᴡꜝͼᴡⱳᴒͼᴐꞌ꞉ꜜ꞉ᴐԜꞌͼᴠᴡᴢᴑᴦͼⱱꜝᴟͼᴒԜᴐⱳͼᴠᴡᴢᴑᴦͼꜞԜᴟᴡ꞉ᴐ꞉ꜞԜꜜᴡ᷅ͼⱴᴟᴒꜟᴢᴒꜜᴡͼᴐꜝꜛꜛᴢꜜ꞉ᴐԜᴡ꞉ꜝꜜͼ
ԝᴒᴡᴤᴒᴒꜜͼᴡⱳᴒͼᴐꞌ꞉ꜜ꞉ᴐԜꞌͼᴠ꞉ᴡᴒͼԜꜜᴑͼᴡⱳᴒͼᴀꜞꜝꜜᴠꜝᴟͼ꞉ᴠͼᴒᴠᴠᴒꜜᴡ꞉ԜꞌͼᴡꜝͼᴒꜜᴠᴢᴟᴒͼᴡⱳԜᴡͼᴡⱳᴒͼᴠԜⱱᴒᴡᴦͼꜝⱱͼᴡⱳᴒͼᴠᴡᴢᴑᴦͼ꞉ᴠͼ
ꜛꜝꜜ꞉ᴡꜝᴟᴒᴑͼԜᴑᴒꜟᴢԜᴡᴒꞌᴦ᷅ͼᴁⱳᴒͼⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟͼᴤ꞉ꞌꞌͼꜛԜꞋᴒͼԜꞌꞌͼԜꜞꜞᴟꜝꜞᴟ꞉ԜᴡᴒͼᴠԜⱱᴒᴡᴦͼԜᴠᴠᴒᴠᴠꜛᴒꜜᴡᴠͼꜝꜜͼԜꜜͼ

Ⱬᴅ᷄᷉Ⱡ᷊᷇
ⱪꞌ꞉ꜜ꞉ᴐԜꞌͼᴁᴟ꞉Ԝꞌͼ͟ᴟꜝᴡꜝᴐꜝꞌⱡͼⱫᴅ᷄᷉Ⱡ᷊᷊᷇᷄᷇
ⱨꜛᴒꜜᴑꜛᴒꜜᴡͼ᷊᷅᷇ͼⱴ꞉ꜜԜꞌⱡͼ᷇ⱠͼꜗԜꜜᴢԜᴟᴦ᷉᷇᷈ⅎ
ⱪꜝꜜⱱ꞉ᴑᴒꜜᴡ꞉Ԝꞌ
͟ԜⱲᴒͼ˲ⅎ
ⱫᴦԜᴥͼⱪꜝᴟꜞ᷅
ꜝꜜⱲꜝ꞉ꜜⱲͼԝԜᴠ꞉ᴠ᷅ͼᴁⱳᴒͼꜚᴒᴑ꞉ᴐԜꞌͼꜚꜝꜜ꞉ᴡꜝᴟͼꜛԜᴦͼᴟᴒᴣ꞉ᴒᴤͼᴠԜⱱᴒᴡᴦͼ꞉ꜜⱱꜝᴟꜛԜᴡ꞉ꜝꜜͼԜᴠͼ꞉ᴡͼԝᴒᴐꜝꜛᴒᴠͼԜᴣԜ꞉ꞌԜԝꞌᴒͼ
ᴡⱳᴟꜝᴢⱲⱳꜝᴢᴡͼᴡⱳᴒͼᴠᴡᴢᴑᴦ᷅
ⱨꞌꞌͼԜᴠꜞᴒᴐᴡᴠͼꜝⱱͼᴡⱳᴒͼᴠᴡᴢᴑᴦͼᴤ꞉ꞌꞌͼԝᴒͼᴐԜᴟᴒⱱᴢꞌꞌᴦͼꜛꜝꜜ꞉ᴡꜝᴟᴒᴑͼᴤ꞉ᴡⱳͼᴟᴒᴠꜞᴒᴐᴡͼᴡꜝͼⱵⱪ͟ͼԜꜜᴑͼᴀ꜡͟ᴠͼⱱꜝᴟͼ
ᴐꜝꜛꜞꞌ꞉Ԝꜜᴐᴒͼᴤ꞉ᴡⱳͼԜꜞꜞꞌ꞉ᴐԜԝꞌᴒͼⱲꜝᴣᴒᴟꜜꜛᴒꜜᴡͼᴟᴒⱲᴢꞌԜᴡ꞉ꜝꜜᴠ᷅ͼᴁⱳᴒͼᴀᴡᴢᴑᴦͼꜚꜝꜜ꞉ᴡꜝᴟͼᴤ꞉ꞌꞌͼԝᴒͼԜꜜͼԜᴢᴡⱳꜝᴟ꞉ᴧᴒᴑͼ
꞉ꜜᴑ꞉ᴣ꞉ᴑᴢԜꞌͼᴑᴒᴠ꞉ⱲꜜԜᴡᴒᴑͼԝᴦͼᴡⱳᴒͼᴀꜞꜝꜜᴠꜝᴟ᷅ͼᴁⱳᴒͼᴀᴡᴢᴑᴦͼꜚꜝꜜ꞉ᴡꜝᴟͼᴤ꞉ꞌꞌͼⱳԜᴣᴒͼԜᴐᴐᴒᴠᴠͼᴡꜝͼԜꞌꞌͼᴟᴒᴐꜝᴟᴑᴠͼ
ꜜᴒᴐᴒᴠᴠԜᴟᴦͼᴡꜝͼᴒꜜᴠᴢᴟᴒͼ꞉ꜜᴡᴒⱲᴟ꞉ᴡᴦͼꜝⱱͼᴡⱳᴒͼᴑԜᴡԜͼԜꜜᴑͼᴤ꞉ꞌꞌͼꜞᴒᴟ꞉ꜝᴑ꞉ᴐԜꞌꞌᴦͼᴟᴒᴣ꞉ᴒᴤͼᴡⱳᴒͼꜞᴟꜝⱲᴟᴒᴠᴠͼꜝⱱͼᴡⱳᴒͼᴠᴡᴢᴑᴦͼ
ᴤ꞉ᴡⱳͼᴡⱳᴒͼⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟ᷅
10.6
Case Report Forms and Study Records
ᴁⱳᴒͼⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟͼᴤ꞉ꞌꞌͼᴒꜜᴠᴢᴟᴒͼᴡⱳᴒͼԜᴐᴐᴢᴟԜᴐᴦԓͼᴐꜝꜛꜞꞌᴒᴡᴒꜜᴒᴠᴠԓͼԜꜜᴑͼᴡ꞉ꜛᴒꞌ꞉ꜜᴒᴠᴠͼꜝⱱͼᴡⱳᴒͼᴑԜᴡԜͼᴟᴒꜞꜝᴟᴡᴒᴑͼᴡꜝͼ
ᴡⱳᴒͼᴀꜞꜝꜜᴠꜝᴟ᷅ͼⱫԜᴡԜͼᴐꜝꞌꞌᴒᴐᴡ꞉ꜝꜜͼꜞᴟꜝᴐᴒᴠᴠᴒᴠͼԜꜜᴑͼꜞᴟꜝᴐᴒᴑᴢᴟᴒᴠͼᴤ꞉ꞌꞌͼԝᴒͼᴟᴒᴣ꞉ᴒᴤᴒᴑͼԜꜜᴑͼᴣԜꞌ꞉ᴑԜᴡᴒᴑͼᴡꜝͼᴒꜜᴠᴢᴟᴒͼ
ᴐꜝꜛꜞꞌᴒᴡᴒꜜᴒᴠᴠԓͼԜᴐᴐᴢᴟԜᴐᴦԓͼᴟᴒꞌ꞉Ԝԝ꞉ꞌ꞉ᴡᴦԓͼԜꜜᴑͼᴐꜝꜜᴠ꞉ᴠᴡᴒꜜᴐᴦ᷅ͼⱨͼᴐꜝꜛꜞꞌᴒᴡᴒͼԜᴢᴑ꞉ᴡͼᴡᴟԜ꞉ꞌͼᴤ꞉ꞌꞌͼԝᴒͼꜛԜ꞉ꜜᴡԜ꞉ꜜᴒᴑͼꜝⱱͼ
ԜꞌꞌͼᴑԜᴡԜͼᴐⱳԜꜜⱲᴒᴠ᷅ͼᴁⱳᴒͼⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟͼꜝᴟͼᴑᴒᴠ꞉Ⱳꜜᴒᴒͼᴤ꞉ꞌꞌͼᴐꜝꜝꜞᴒᴟԜᴡᴒͼᴤ꞉ᴡⱳͼᴡⱳᴒͼᴀꜞꜝꜜᴠꜝᴟᶳᴠͼᴟᴒꜞᴟᴒᴠᴒꜜᴡԜᴡ꞉ᴣᴒӿᴠԐͼ
ⱱꜝᴟͼᴡⱳᴒͼꜞᴒᴟ꞉ꜝᴑ꞉ᴐͼᴟᴒᴣ꞉ᴒᴤͼꜝⱱͼᴠᴡᴢᴑᴦͼᴑꜝᴐᴢꜛᴒꜜᴡᴠͼᴡꜝͼᴒꜜᴠᴢᴟᴒͼᴡⱳᴒͼԜᴐᴐᴢᴟԜᴐᴦͼԜꜜᴑͼᴐꜝꜛꜞꞌᴒᴡᴒꜜᴒᴠᴠͼꜝⱱͼᴡⱳᴒͼᴑԜᴡԜͼ
ᴐԜꜞᴡᴢᴟᴒͼᴠᴦᴠᴡᴒꜛͼԜᴡͼᴒԜᴐⱳͼᴠᴐⱳᴒᴑᴢꞌᴒᴑͼꜛꜝꜜ꞉ᴡꜝᴟ꞉ꜜⱲͼᴣ꞉ᴠ꞉ᴡ᷅
ⱬꞌᴒᴐᴡᴟꜝꜜ꞉ᴐͼᴐꜝꜜᴠ꞉ᴠᴡᴒꜜᴐᴦͼᴐⱳᴒᴐꞋᴠͼԜꜜᴑͼꜛԜꜜᴢԜꞌͼᴟᴒᴣ꞉ᴒᴤͼᴤ꞉ꞌꞌͼԝᴒͼᴢᴠᴒᴑͼᴡꜝͼ꞉ᴑᴒꜜᴡ꞉ⱱᴦͼԜꜜᴦͼᴒᴟᴟꜝᴟᴠͼꜝᴟͼ
꞉ꜜᴐꜝꜜᴠ꞉ᴠᴡᴒꜜᴐ꞉ᴒᴠͼ꞉ꜜͼᴡⱳᴒͼᴑԜᴡԜ᷅ͼᴁⱳ꞉ᴠͼ꞉ꜜⱱꜝᴟꜛԜᴡ꞉ꜝꜜͼᴤ꞉ꞌꞌͼԝᴒͼꜞᴟꜝᴣ꞉ᴑᴒᴑͼᴡꜝͼᴡⱳᴒͼᴐꞌ꞉ꜜ꞉ᴐԜꞌͼᴠ꞉ᴡᴒᴠͼԝᴦͼꜛᴒԜꜜᴠͼꜝⱱͼ
ᴒꞌᴒᴐᴡᴟꜝꜜ꞉ᴐͼꜝᴟͼꜛԜꜜᴢԜꞌͼꜟᴢᴒᴟ꞉ᴒᴠ᷅
ᴁⱳᴒͼⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟͼꜝᴟͼᴑᴒᴠ꞉Ⱳꜜᴒᴒͼᴤ꞉ꞌꞌͼꜞᴟᴒꜞԜᴟᴒͼԜꜜᴑͼꜛԜ꞉ꜜᴡԜ꞉ꜜͼԜᴑᴒꜟᴢԜᴡᴒͼԜꜜᴑͼԜᴐᴐᴢᴟԜᴡᴒͼᴠᴡᴢᴑᴦͼᴑꜝᴐᴢꜛᴒꜜᴡᴠͼ
ӿꜛᴒᴑ꞉ᴐԜꞌͼᴟᴒᴐꜝᴟᴑᴠԓͼⱬⱪⱵᴠԓͼⱨⱬͼԜꜜᴑͼᴐꜝꜜᴐꜝꜛ꞉ᴡԜꜜᴡͼꜛᴒᴑ꞉ᴐԜᴡ꞉ꜝꜜͼᴟᴒꜞꜝᴟᴡ꞉ꜜⱲԓͼᴠꜝᴢᴟᴐᴒͼᴑԜᴡԜͼᴐꜝꞌꞌᴒᴐᴡ꞉ꜝꜜͼⱱꜝᴟꜛᴠԓͼ
ᴒᴡᴐ᷅Ԑͼᴑᴒᴠ꞉ⱲꜜᴒᴑͼᴡꜝͼᴟᴒᴐꜝᴟᴑͼԜꞌꞌͼꜝԝᴠᴒᴟᴣԜᴡ꞉ꜝꜜᴠͼԜꜜᴑͼꜝᴡⱳᴒᴟͼꜞᴒᴟᴡ꞉ꜜᴒꜜᴡͼᴑԜᴡԜͼⱱꜝᴟͼᴒԜᴐⱳͼᴠᴢԝ꞊ᴒᴐᴡͼᴟᴒᴐᴒ꞉ᴣ꞉ꜜⱲͼ
ᴟԜꜜᴑꜝꜛ꞉ᴧᴒᴑͼᴠᴡᴢᴑᴦͼᴑᴢⱲ᷅
ᴁⱳᴒͼⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟͼᴤ꞉ꞌꞌͼԜꞌꞌꜝᴤͼᴀꜞꜝꜜᴠꜝᴟͼᴟᴒꜞᴟᴒᴠᴒꜜᴡԜᴡ꞉ᴣᴒᴠԓͼᴐꜝꜜᴡᴟԜᴐᴡͼᴑᴒᴠ꞉ⱲꜜᴒᴒᴠԓͼԜᴢᴡⱳꜝᴟ꞉ᴧᴒᴑͼᴟᴒⱲᴢꞌԜᴡꜝᴟᴦͼ
Ԝᴢᴡⱳꜝᴟ꞉ᴡᴦͼ꞉ꜜᴠꜞᴒᴐᴡꜝᴟᴠԓͼԜꜜᴑͼᴡⱳᴒͼⱷϸⱩ᷆ϸⱬⱩ᷆ⱷⱬⱪͼᴡꜝͼⱳԜᴣᴒͼᴑ꞉ᴟᴒᴐᴡͼԜᴐᴐᴒᴠᴠͼᴡꜝͼԜꞌꞌͼᴑꜝᴐᴢꜛᴒꜜᴡᴠͼꜞᴒᴟᴡԜ꞉ꜜ꞉ꜜⱲͼᴡꜝͼ
ᴡⱳᴒͼᴠᴡᴢᴑᴦ᷅
ⱨͼᴁᴟ꞉ԜꞌͼꜚԜᴠᴡᴒᴟͼⱴ꞉ꞌᴒͼᴤ꞉ꞌꞌͼԝᴒͼꜛԜ꞉ꜜᴡԜ꞉ꜜᴒᴑͼԝᴦͼᴡⱳᴒͼᴀꜞꜝꜜᴠꜝᴟͼӿꜝᴟͼᴑᴒᴠ꞉ⱲꜜᴒᴒԐ᷅ͼⱨꞌꞌͼᴑꜝᴐᴢꜛᴒꜜᴡᴠͼԜꜜᴑͼꜝᴡⱳᴒᴟͼ
ꜛԜᴡᴒᴟ꞉ԜꞌᴠͼᴡⱳԜᴡͼꜞᴒᴟᴡԜ꞉ꜜͼᴡꜝͼᴡⱳᴒͼᴐꜝꜜᴑᴢᴐᴡͼꜝⱱͼᴡⱳᴒͼᴡᴟ꞉ԜꞌԓͼꜟᴢԜꞌ꞉ᴡᴦͼꜝⱱͼᴡⱳᴒͼᴑԜᴡԜԓͼԜꜜᴑͼᴐꜝꜛꜞꞌ꞉Ԝꜜᴐᴒͼᴤ꞉ᴡⱳͼⱵⱪ͟ᴠͼ
ᴤ꞉ꞌꞌͼԝᴒͼᴐꜝꞌꞌᴒᴐᴡᴒᴑͼ꞉ꜜͼᴡⱳᴒͼᴁᴟ꞉ԜꞌͼꜚԜᴠᴡᴒᴟͼⱴ꞉ꞌᴒ᷅
10.7
Data Safety Monitoring Board 
ⱨꜜͼ꞉ꜜᴑᴒꜞᴒꜜᴑᴒꜜᴡͼⱫᴀꜚⱩͼᴤ꞉ꞌꞌͼԝᴒͼᴒᴠᴡԜԝꞌ꞉ᴠⱳᴒᴑͼᴡꜝͼꜞᴟꜝᴣ꞉ᴑᴒͼԜꜜͼꜝꜜⱲꜝ꞉ꜜⱲԓͼ꞉ꜜᴑᴒꜞᴒꜜᴑᴒꜜᴡͼᴟᴒᴣ꞉ᴒᴤͼԜꜜᴑͼ
ԜᴠᴠᴒᴠᴠꜛᴒꜜᴡͼꜝⱱͼᴡⱳᴒͼᴠԜⱱᴒᴡᴦͼᴑԜᴡԜԓͼԜꜜᴑͼᴡꜝͼᴠԜⱱᴒⱲᴢԜᴟᴑͼᴡⱳᴒͼ꞉ꜜᴡᴒᴟᴒᴠᴡᴠͼԜꜜᴑͼᴠԜⱱᴒᴡᴦͼꜝⱱͼᴡⱳᴒͼꜞԜᴟᴡ꞉ᴐ꞉ꜞԜᴡ꞉ꜜⱲͼ
ꜞԜᴡ꞉ᴒꜜᴡᴠͼ꞉ꜜͼᴡⱳᴒͼᴠᴡᴢᴑᴦ᷅ͼ
ᴁⱳᴒͼⱫᴀꜚⱩͼᴤ꞉ꞌꞌͼԜᴑⱳᴒᴟᴒͼᴡꜝͼԜͼꜞᴟꜝᴠꜞᴒᴐᴡ꞉ᴣᴒꞌᴦͼᴑᴒᴡᴒᴟꜛ꞉ꜜᴒᴑͼⱪⱳԜᴟᴡᴒᴟԓͼᴤⱳ꞉ᴐⱳͼᴤ꞉ꞌꞌͼԝᴒͼᴤᴟ꞉ᴡᴡᴒꜜͼԝᴦͼᴡⱳᴒͼ
ᴀꜞꜝꜜᴠꜝᴟͼԜꜜᴑͼԜꜞꜞᴟꜝᴣᴒᴑͼԝᴦͼᴡⱳᴒͼⱫᴀꜚⱩ᷅ͼᴁⱳᴒͼⱪⱳԜᴟᴡᴒᴟͼᴤ꞉ꞌꞌͼᴑᴒⱱ꞉ꜜᴒͼᴡⱳᴒͼᴟᴒᴠꜞꜝꜜᴠ꞉ԝ꞉ꞌ꞉ᴡ꞉ᴒᴠͼꜝⱱͼᴡⱳᴒͼⱫᴀꜚⱩͼ
ԜꜜᴑͼᴀꜞꜝꜜᴠꜝᴟԓͼᴡⱳᴒͼꜜᴢꜛԝᴒᴟͼԜꜜᴑͼᴡ꞉ꜛ꞉ꜜⱲͼꜝⱱͼᴡⱳᴒͼⱫᴀꜚⱩͼꜛᴒᴒᴡ꞉ꜜⱲᴠԓͼᴡⱳᴒͼᴐꜝꜜᴑᴢᴐᴡͼꜝⱱͼᴡⱳᴒͼꜛᴒᴒᴡ꞉ꜜⱲᴠԓͼԜꜜᴑͼ
ᴡⱳᴒͼᴑԜᴡԜͼᴠᴒᴡᴠͼᴡꜝͼԝᴒͼᴟᴒᴣ꞉ᴒᴤᴒᴑͼԝᴦͼᴡⱳᴒͼⱫᴀꜚⱩ᷅ⱴᴢᴟᴡⱳᴒᴟͼᴑᴒᴡԜ꞉ꞌᴠͼᴟᴒⱲԜᴟᴑ꞉ꜜⱲͼᴡⱳᴒͼⱫᴀꜚⱩͼᴐԜꜜͼԝᴒͼⱱꜝᴢꜜᴑͼ꞉ꜜͼ
ᴡⱳᴒͼⱫᴀꜚⱩͼᴐⱳԜᴟᴡᴒᴟ᷅

Ⱬᴅ᷄᷉Ⱡ᷊᷇
ⱪꞌ꞉ꜜ꞉ᴐԜꞌͼᴁᴟ꞉Ԝꞌͼ͟ᴟꜝᴡꜝᴐꜝꞌⱡͼⱫᴅ᷄᷉Ⱡ᷊᷊᷇᷄᷇
ⱨꜛᴒꜜᴑꜛᴒꜜᴡͼ᷊᷅᷇ͼⱴ꞉ꜜԜꞌⱡͼ᷇ⱠͼꜗԜꜜᴢԜᴟᴦ᷉᷇᷈ⅎ
ⱪꜝꜜⱱ꞉ᴑᴒꜜᴡ꞉Ԝꞌ
͟ԜⱲᴒͼ˲˲
ⱫᴦԜᴥͼⱪꜝᴟꜞ᷅
10.8
Protocol Violations/Deviations
ᴁⱳᴒͼⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟͼᴤ꞉ꞌꞌͼԝᴒͼ꞉ꜜᴠᴡᴟᴢᴐᴡᴒᴑͼꜜꜝᴡͼᴡꜝͼᴑᴒᴣ꞉ԜᴡᴒͼⱱᴟꜝꜛͼᴡⱳᴒͼꜞᴟꜝᴡꜝᴐꜝꞌԓͼᴒᴥᴐᴒꜞᴡͼᴤⱳᴒᴟᴒͼꜜᴒᴐᴒᴠᴠԜᴟᴦͼᴡꜝͼ
ᴒꞌ꞉ꜛ꞉ꜜԜᴡᴒͼԜꜜͼ꞉ꜛꜛᴒᴑ꞉ԜᴡᴒͼⱳԜᴧԜᴟᴑᴡꜝͼᴠᴡᴢᴑᴦͼꜞԜᴟᴡ꞉ᴐ꞉ꜞԜꜜᴡᴠ᷅ͼᴀⱳꜝᴢꞌᴑͼꜝᴡⱳᴒᴟͼᴢꜜᴒᴥꜞᴒᴐᴡᴒᴑͼᴐ꞉ᴟᴐᴢꜛᴠᴡԜꜜᴐᴒᴠͼ
Ԝᴟ꞉ᴠᴒͼᴡⱳԜᴡͼᴤ꞉ꞌꞌͼᴟᴒꜟᴢ꞉ᴟᴒͼᴑᴒᴣ꞉Ԝᴡ꞉ꜝꜜͼⱱᴟꜝꜛͼꜞᴟꜝᴡꜝᴐꜝꞌ᷄ᴠꜞᴒᴐ꞉ⱱ꞉ᴐͼꜞᴟꜝᴐᴒᴑᴢᴟᴒᴠԓͼᴡⱳᴒͼⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟͼᴠⱳꜝᴢꞌᴑͼ
ᴐꜝꜜᴡԜᴐᴡͼᴡⱳᴒ꞉ᴟͼᴀꜞꜝꜜᴠꜝᴟͼᴟᴒꜞᴟᴒᴠᴒꜜᴡԜᴡ꞉ᴣᴒͼᴡꜝͼᴑ꞉ᴠᴐᴢᴠᴠͼᴡⱳᴒͼԜꜞꜞᴟꜝꜞᴟ꞉ԜᴡᴒͼᴐꜝᴢᴟᴠᴒͼꜝⱱͼԜᴐᴡ꞉ꜝꜜ᷅ͼ
ᴁⱳᴒͼⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟͼᴠⱳꜝᴢꞌᴑͼᴑꜝᴐᴢꜛᴒꜜᴡͼԜꞌꞌͼꜞᴟꜝᴡꜝᴐꜝꞌͼᴑᴒᴣ꞉Ԝᴡ꞉ꜝꜜᴠ᷆ᴣ꞉ꜝꞌԜᴡ꞉ꜝꜜᴠͼ꞉ꜜͼᴡⱳᴒͼᴠᴢԝ꞊ᴒᴐᴡᶳᴠͼᴒⱪϸⱴͼԜꜜᴑͼ
ᴠꜝᴢᴟᴐᴒͼᴑꜝᴐᴢꜛᴒꜜᴡᴠͼꜝᴟͼᴡⱳᴒͼⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟͼᴀ꞉ᴡᴒͼⱴ꞉ꞌᴒͼ꞉ⱱͼԜꜞꜞᴟꜝꜞᴟ꞉Ԝᴡᴒ᷅ͼⱷꜜͼᴡⱳᴒͼᴒᴣᴒꜜᴡͼꜝⱱͼԜͼᴠ꞉Ⱳꜜ꞉ⱱ꞉ᴐԜꜜᴡͼ
ᴑᴒᴣ꞉Ԝᴡ꞉ꜝꜜ᷆ᴣ꞉ꜝꞌԜᴡ꞉ꜝꜜԓͼᴡⱳᴒͼⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟͼᴠⱳꜝᴢꞌᴑͼꜜꜝᴡ꞉ⱱᴦͼᴡⱳᴒͼᴀꜞꜝꜜᴠꜝᴟͼᴟᴒꜞᴟᴒᴠᴒꜜᴡԜᴡ꞉ᴣᴒ᷅ͼᴀ꞉Ⱳꜜ꞉ⱱ꞉ᴐԜꜜᴡͼ
ᴑᴒᴣ꞉Ԝᴡ꞉ꜝꜜᴠ᷆ᴣ꞉ꜝꞌԜᴡ꞉ꜝꜜᴠͼ꞉ꜜᴐꞌᴢᴑᴒԓͼԝᴢᴡͼԜᴟᴒͼꜜꜝᴡͼꞌ꞉ꜛ꞉ᴡᴒᴑͼᴡꜝͼᴡⱳꜝᴠᴒͼᴡⱳԜᴡͼ꞉ꜜᴐᴟᴒԜᴠᴒͼᴡⱳᴒͼⱳᴒԜꞌᴡⱳͼᴟ꞉ᴠꞋͼᴡꜝͼᴡⱳᴒͼ
ᴠᴢԝ꞊ᴒᴐᴡԓͼꜝᴟͼᴐꜝꜜⱱꜝᴢꜜᴑͼ꞉ꜜᴡᴒᴟꜞᴟᴒᴡԜᴡ꞉ꜝꜜͼꜝⱱͼꜞᴟ꞉ꜛԜᴟᴦͼᴠᴡᴢᴑᴦͼԜᴠᴠᴒᴠᴠꜛᴒꜜᴡᴠ᷅ͼᴁⱳᴒͼⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟͼᴤ꞉ꞌꞌͼꜞᴟꜝꜛꜞᴡꞌᴦͼ
ᴟᴒꜞꜝᴟᴡͼԜꞌꞌͼᴐⱳԜꜜⱲᴒᴠͼ꞉ꜜͼᴟᴒᴠᴒԜᴟᴐⱳͼԜᴐᴡ꞉ᴣ꞉ᴡᴦͼԜꜜᴑͼԜꞌꞌͼᴢꜜԜꜜᴡ꞉ᴐ꞉ꜞԜᴡᴒᴑͼꜞᴟꜝԝꞌᴒꜛᴠͼ꞉ꜜᴣꜝꞌᴣ꞉ꜜⱲͼᴟ꞉ᴠꞋᴠͼᴡꜝͼⱳᴢꜛԜꜜͼ
ᴠᴢԝ꞊ᴒᴐᴡᴠͼꜝᴟͼꜝᴡⱳᴒᴟᴠͼᴡꜝͼⱳ꞉ᴠͼꜝᴟͼⱳᴒᴟͼⱷϸⱩ᷆ϸⱬⱩ᷆ⱷⱬⱪ᷅
10.9
Premature Closure of the Study
ⱷⱱͼᴡⱳᴒͼᴀꜞꜝꜜᴠꜝᴟԓͼⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟԓͼⱫᴀꜚⱩԓͼꜝᴟͼᴟᴒⱲᴢꞌԜᴡꜝᴟᴦͼԜᴢᴡⱳꜝᴟ꞉ᴡ꞉ᴒᴠͼᴑ꞉ᴠᴐꜝᴣᴒᴟͼᴐꜝꜜᴑ꞉ᴡ꞉ꜝꜜᴠͼԜᴟ꞉ᴠ꞉ꜜⱲͼᴑᴢᴟ꞉ꜜⱲͼ
ᴡⱳᴒͼᴠᴡᴢᴑᴦͼᴤⱳ꞉ᴐⱳͼ꞉ꜜᴑ꞉ᴐԜᴡᴒͼᴡⱳԜᴡͼᴡⱳᴒͼᴐꞌ꞉ꜜ꞉ᴐԜꞌͼ꞉ꜜᴣᴒᴠᴡ꞉ⱲԜᴡ꞉ꜝꜜͼᴠⱳꜝᴢꞌᴑͼԝᴒͼⱳԜꞌᴡᴒᴑͼᴑᴢᴒͼᴡꜝͼԜꜜͼᴢꜜԜᴐᴐᴒꜞᴡԜԝꞌᴒͼ
ꜞԜᴡ꞉ᴒꜜᴡͼᴟ꞉ᴠꞋԓͼᴡⱳᴒͼᴠᴡᴢᴑᴦͼꜛԜᴦͼԝᴒͼᴡᴒᴟꜛ꞉ꜜԜᴡᴒᴑͼꜝᴣᴒᴟԜꞌꞌͼꜝᴟͼԜᴡͼԜͼᴠꜞᴒᴐ꞉ⱱ꞉ᴐͼᴠ꞉ᴡᴒͼԜⱱᴡᴒᴟͼԜꜞꜞᴟꜝꜞᴟ꞉Ԝᴡᴒͼ
ᴐꜝꜜᴠᴢꞌᴡԜᴡ꞉ꜝꜜͼԝᴒᴡᴤᴒᴒꜜͼᴡⱳᴒͼᴀꜞꜝꜜᴠꜝᴟͼԜꜜᴑͼᴡⱳᴒͼⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟӿᴠԐ᷅ͼⱷꜜͼԜᴑᴑ꞉ᴡ꞉ꜝꜜԓͼԜͼᴑᴒᴐ꞉ᴠ꞉ꜝꜜͼꜝꜜͼᴡⱳᴒͼꜞԜᴟᴡͼꜝⱱͼ
ᴡⱳᴒͼᴀꜞꜝꜜᴠꜝᴟͼᴡꜝͼᴠᴢᴠꜞᴒꜜᴑͼꜝᴟͼᴑ꞉ᴠᴐꜝꜜᴡ꞉ꜜᴢᴒͼᴑᴒᴣᴒꞌꜝꜞꜛᴒꜜᴡͼꜝⱱͼᴡⱳᴒͼ꞉ꜜᴣᴒᴠᴡ꞉ⱲԜᴡ꞉ꜝꜜԜꞌͼꜞᴟꜝᴑᴢᴐᴡͼꜛԜᴦͼԝᴒͼꜛԜᴑᴒͼ
ԜᴡͼԜꜜᴦͼᴡ꞉ꜛᴒ᷅ͼⱪꜝꜜᴑ꞉ᴡ꞉ꜝꜜᴠͼᴡⱳԜᴡͼꜛԜᴦͼᴤԜᴟᴟԜꜜᴡͼᴡᴒᴟꜛ꞉ꜜԜᴡ꞉ꜝꜜͼꜝⱱͼᴡⱳᴒͼᴠᴡᴢᴑᴦͼꜝᴟͼᴠ꞉ᴡᴒͼ꞉ꜜᴐꞌᴢᴑᴒԓͼԝᴢᴡͼԜᴟᴒͼꜜꜝᴡͼ
ꞌ꞉ꜛ꞉ᴡᴒᴑͼᴡꜝԓͼᴡⱳᴒͼⱱꜝꞌꞌꜝᴤ꞉ꜜⱲⱡ
ᶄ
ᴁⱳᴒͼᴑ꞉ᴠᴐꜝᴣᴒᴟᴦͼꜝⱱͼԜꜜͼᴢꜜᴒᴥꜞᴒᴐᴡᴒᴑԓͼᴠ꞉Ⱳꜜ꞉ⱱ꞉ᴐԜꜜᴡԓͼꜝᴟͼᴢꜜԜᴐᴐᴒꜞᴡԜԝꞌᴒͼᴟ꞉ᴠꞋͼᴡꜝͼᴡⱳᴒͼꜞԜᴡ꞉ᴒꜜᴡᴠͼᴒꜜᴟꜝꞌꞌᴒᴑͼ꞉ꜜͼ
ᴡⱳᴒͼᴠᴡᴢᴑᴦ
ᶄ
ⱴԜ꞉ꞌᴢᴟᴒͼꜝⱱͼᴡⱳᴒͼⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟͼᴡꜝͼᴐꜝꜛꜞꞌᴦͼᴤ꞉ᴡⱳͼꜞᴒᴟᴡ꞉ꜜᴒꜜᴡͼⱲꞌꜝԝԜꞌͼᴟᴒⱲᴢꞌԜᴡ꞉ꜝꜜᴠ
ᶄ
ᴀᴢԝꜛ꞉ᴠᴠ꞉ꜝꜜͼꜝⱱͼꞋꜜꜝᴤ꞉ꜜⱲꞌᴦͼⱱԜꞌᴠᴒͼ꞉ꜜⱱꜝᴟꜛԜᴡ꞉ꜝꜜͼⱱᴟꜝꜛͼᴡⱳᴒͼᴠᴡᴢᴑᴦͼᴠ꞉ᴡᴒͼᴡꜝͼᴡⱳᴒͼᴀꜞꜝꜜᴠꜝᴟͼꜝᴟͼꜝᴡⱳᴒᴟͼ
ꜞᴒᴟᴡ꞉ꜜᴒꜜᴡͼᴟᴒⱲᴢꞌԜᴡꜝᴟᴦͼԜᴢᴡⱳꜝᴟ꞉ᴡ꞉ᴒᴠ
ᶄ
ⱷꜜᴠᴢⱱⱱ꞉ᴐ꞉ᴒꜜᴡͼԜᴑⱳᴒᴟᴒꜜᴐᴒͼԝᴦͼᴡⱳᴒͼⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟͼᴡꜝͼꜞᴟꜝᴡꜝᴐꜝꞌͼᴟᴒꜟᴢ꞉ᴟᴒꜛᴒꜜᴡᴠ
10.10 Access to Source Documentation and On-Site Audits
ϸᴒⱲᴢꞌԜᴡꜝᴟᴦͼԜⱲᴒꜜᴐ꞉ᴒᴠͼꜛԜᴦͼᴟᴒꜟᴢᴒᴠᴡͼԜᴐᴐᴒᴠᴠͼᴡꜝͼԜꞌꞌͼᴠᴡᴢᴑᴦͼᴟᴒᴐꜝᴟᴑᴠԓͼ꞉ꜜᴐꞌᴢᴑ꞉ꜜⱲͼᴠꜝᴢᴟᴐᴒͼᴑꜝᴐᴢꜛᴒꜜᴡᴠԓͼⱱꜝᴟͼ
꞉ꜜᴠꜞᴒᴐᴡ꞉ꜝꜜͼԜꜜᴑͼᴐꜝꜞᴦ꞉ꜜⱲԓͼ꞉ꜜͼꞋᴒᴒꜞ꞉ꜜⱲͼᴤ꞉ᴡⱳͼᴐꜝᴢꜜᴡᴟᴦͼᴟᴒⱲᴢꞌԜᴡ꞉ꜝꜜᴠ᷅ͼᴁⱳᴒͼⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟͼᴠⱳꜝᴢꞌᴑͼ
꞉ꜛꜛᴒᴑ꞉Ԝᴡᴒꞌᴦͼꜜꜝᴡ꞉ⱱᴦͼᴡⱳᴒͼᴀꜞꜝꜜᴠꜝᴟͼᴟᴒꜞᴟᴒᴠᴒꜜᴡԜᴡ꞉ᴣᴒͼꜝⱱͼԜꜜᴦͼԜꜜꜜꜝᴢꜜᴐᴒᴑͼꜝᴟͼᴢꜜԜꜜꜜꜝᴢꜜᴐᴒᴑͼᴟᴒⱲᴢꞌԜᴡꜝᴟᴦͼ
ԜⱲᴒꜜᴐᴦͼ꞉ꜜᴠꜞᴒᴐᴡ꞉ꜝꜜᴠ᷅ͼⱨꜜͼԜᴢᴑ꞉ᴡ꞉ꜜⱲͼ꞉ꜜᴠꜞᴒᴐᴡ꞉ꜝꜜͼꜛԜᴦͼԜꞌᴠꜝͼԝᴒͼᴐꜝꜜᴑᴢᴐᴡᴒᴑͼԝᴦͼᴡⱳᴒͼᴀꜞꜝꜜᴠꜝᴟͼᴟᴒꜞᴟᴒᴠᴒꜜᴡԜᴡ꞉ᴣᴒͼ
ꜝᴟͼᴑᴒᴠ꞉Ⱳꜜᴒᴒ᷅ͼⱨꜜᴦͼԜᴠꜞᴒᴐᴡͼꜝⱱͼᴡⱳᴒͼᴡᴟ꞉ԜꞌͼꜛԜᴦԝᴒͼᴠᴢԝ꞊ᴒᴐᴡͼᴡꜝͼԜᴢᴑ꞉ᴡͼԝᴦͼᴡⱳᴒͼᴀꜞꜝꜜᴠꜝᴟͼԜꜜᴑ᷆ꜝᴟͼ꞉ꜜᴠꜞᴒᴐᴡ꞉ꜝꜜͼԝᴦͼ
ᴟᴒⱲᴢꞌԜᴡꜝᴟᴦͼԜᴢᴡⱳꜝᴟ꞉ᴡ꞉ᴒᴠͼꜝᴟͼᴡⱳᴒͼⱷϸⱩ᷆ϸⱬⱩ᷆ⱷⱬⱪ᷅ͼᴀᴢᴐⱳͼԜᴢᴑ꞉ᴡᴠ᷆꞉ꜜᴠꜞᴒᴐᴡ꞉ꜝꜜᴠͼꜛԜᴦͼᴡԜꞋᴒͼꜞꞌԜᴐᴒͼԜᴡͼᴡⱳᴒͼ
ᴀꜞꜝꜜᴠꜝᴟᶳᴠͼᴠ꞉ᴡᴒӿᴠԐԓͼᴡⱳᴒͼⱪϸ꜡ԓͼꜝᴟͼԜᴡͼᴡⱳᴒͼᴐꞌ꞉ꜜ꞉ᴐԜꞌͼᴠ꞉ᴡᴒᴠԓͼ꞉ꜜᴐꞌᴢᴑ꞉ꜜⱲͼꞌԜԝꜝᴟԜᴡꜝᴟ꞉ᴒᴠԓͼꜞⱳԜᴟꜛԜᴐ꞉ᴒᴠͼԜꜜᴑͼԜꜜᴦͼ
ꜝᴡⱳᴒᴟͼⱱԜᴐ꞉ꞌ꞉ᴡ꞉ᴒᴠͼᴢᴠᴒᴑͼⱱꜝᴟͼᴡⱳᴒͼᴠᴡᴢᴑᴦ᷅ͼ

Ⱬᴅ᷄᷉Ⱡ᷊᷇
ⱪꞌ꞉ꜜ꞉ᴐԜꞌͼᴁᴟ꞉Ԝꞌͼ͟ᴟꜝᴡꜝᴐꜝꞌⱡͼⱫᴅ᷄᷉Ⱡ᷊᷊᷇᷄᷇
ⱨꜛᴒꜜᴑꜛᴒꜜᴡͼ᷊᷅᷇ͼⱴ꞉ꜜԜꞌⱡͼ᷇ⱠͼꜗԜꜜᴢԜᴟᴦ᷉᷇᷈ⅎ
ⱪꜝꜜⱱ꞉ᴑᴒꜜᴡ꞉Ԝꞌ
͟ԜⱲᴒͼ˲Ⱡ
ⱫᴦԜᴥͼⱪꜝᴟꜞ᷅
ᴁⱳᴒͼⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟͼᴤ꞉ꞌꞌͼԝᴒͼᴟᴒᴠꜞꜝꜜᴠ꞉ԝꞌᴒͼⱱꜝᴟͼᴡⱳᴒͼԜᴐᴐᴢᴟԜᴐᴦͼꜝⱱͼᴡⱳᴒͼᴑԜᴡԜͼᴒꜜᴡᴒᴟᴒᴑͼ꞉ꜜͼᴡⱳᴒͼᴒⱪϸⱴ᷅ͼᴁⱳᴒͼ
ⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟͼᴤ꞉ꞌꞌͼꜞᴒᴟꜛ꞉ᴡͼᴡⱳᴒͼᴑᴒᴠ꞉ⱲꜜԜᴡᴒᴑͼᴀꜞꜝꜜᴠꜝᴟͼᴟᴒꜞᴟᴒᴠᴒꜜᴡԜᴡ꞉ᴣᴒᴠͼԜꜜᴑͼᴟᴒⱲᴢꞌԜᴡꜝᴟᴦͼԝꜝᴑ꞉ᴒᴠͼᴡꜝͼⱳԜᴣᴒͼ
ᴑ꞉ᴟᴒᴐᴡͼԜᴐᴐᴒᴠᴠͼᴡꜝͼᴡⱳᴒͼᴠꜝᴢᴟᴐᴒͼᴑꜝᴐᴢꜛᴒꜜᴡᴠͼᴡꜝͼᴣᴒᴟ꞉ⱱᴦͼᴑԜᴡԜͼᴟᴒꜞᴟᴒᴠᴒꜜᴡᴒᴑͼ꞉ꜜͼᴡⱳᴒͼᴒⱪϸⱴ᷅
10.11 Data Generation and Analysis
ᴁⱳ꞉ᴠͼᴠᴡᴢᴑᴦͼᴤ꞉ꞌꞌͼԝᴒͼꜞᴒᴟⱱꜝᴟꜛᴒᴑͼ꞉ꜜͼԜᴐᴐꜝᴟᴑԜꜜᴐᴒͼᴤ꞉ᴡⱳᴟᴒⱲᴢꞌԜᴡꜝᴟᴦͼᴟᴒꜟᴢ꞉ᴟᴒꜛᴒꜜᴡᴠͼꜝᴢᴡꞌ꞉ꜜᴒᴑͼ꞉ꜜͼⱴꜝꜝᴑͼԜꜜᴑͼ
ⱫᴟᴢⱲͼⱨᴑꜛ꞉ꜜ꞉ᴠᴡᴟԜᴡ꞉ꜝꜜͼӿⱴⱫⱨԐ ᷉᷈ⱪⱴϸ ͟Ԝᴟᴡͼ᷿᷇ԓͼ᷉᷈ͼⱪⱴϸ ͟Ԝᴟᴡͼ᷿᷾ԓͼ᷉᷈ͼⱪⱴϸ ͟Ԝᴟᴡͼ᷿⅍ԓͼ᷉᷈ⱪⱴϸ ͟Ԝᴟᴡ᷊᷈᷉ͼ
Ԝꜜᴑͼ᷉᷈ͼⱪⱴϸ ͟Ԝᴟᴡͼ᷈᷈ͼԜᴠͼᴤᴒꞌꞌͼԜᴠͼᴡⱳᴒͼⱷⱪⱶͼⱵⱪ͟ͼⱬ⅍ͼⱵᴢ꞉ᴑᴒꞌ꞉ꜜᴒᴠ᷅ͼᴁⱳᴒͼᴠᴡᴢᴑᴦͼꜛꜝꜜ꞉ᴡꜝᴟᴠͼᴤ꞉ꞌꞌͼꜛᴒᴒᴡͼᴤ꞉ᴡⱳͼ
ᴡⱳᴒͼⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟᴠͼԜꜜᴑͼᴠᴡԜⱱⱱͼᴠⱳꜝᴟᴡꞌᴦͼԝᴒⱱꜝᴟᴒͼᴡⱳᴒͼᴠᴡԜᴟᴡͼꜝⱱͼᴡⱳᴒͼᴡᴟ꞉Ԝꞌͼᴡꜝͼᴟᴒᴣ꞉ᴒᴤͼᴡⱳᴒͼꜞᴟꜝᴐᴒᴑᴢᴟᴒᴠͼⱱꜝᴟͼᴠᴡᴢᴑᴦͼ
ᴐꜝꜜᴑᴢᴐᴡͼԜꜜᴑͼᴑꜝᴐᴢꜛᴒꜜᴡԜᴡ꞉ꜝꜜ᷅ͼⱫᴢᴟ꞉ꜜⱲͼᴡⱳᴒͼᴠᴡᴢᴑᴦԓͼᴡⱳᴒͼꜛꜝꜜ꞉ᴡꜝᴟᴠͼᴤ꞉ꞌꞌͼᴣ꞉ᴠ꞉ᴡͼᴡⱳᴒͼᴠ꞉ᴡᴒᴠͼᴡꜝͼᴣᴒᴟ꞉ⱱᴦͼᴟᴒᴐꜝᴟᴑͼ
Ꞌᴒᴒꜞ꞉ꜜⱲͼԜꜜᴑͼԜᴑⱳᴒᴟᴒꜜᴐᴒͼᴡꜝͼᴡⱳᴒͼꜞᴟꜝᴡꜝᴐꜝꞌ᷅ͼⱴꜝᴟͼᴡⱳ꞉ᴠͼᴠᴡᴢᴑᴦԓͼᴒⱪϸⱴᴠͼᴤ꞉ꞌꞌͼԝᴒͼᴢᴠᴒᴑ᷅ͼᴁⱳᴒͼꜛꜝꜜ꞉ᴡꜝᴟᴠͼᴤ꞉ꞌꞌͼ
ᴐꜝꜜᴑᴢᴐᴡͼ᷈᷇᷇Ӽͼᴠꜝᴢᴟᴐᴒͼᴑꜝᴐᴢꜛᴒꜜᴡͼᴣᴒᴟ꞉ⱱ꞉ᴐԜᴡ꞉ꜝꜜͼԝᴦͼᴐꜝꜛꜞԜᴟ꞉ꜜⱲͼᴡⱳᴒͼᴒⱪϸⱴᴠͼᴤ꞉ᴡⱳͼᴡⱳᴒͼᴠꜝᴢᴟᴐᴒͼᴑꜝᴐᴢꜛᴒꜜᴡᴠͼ
ᴡꜝͼᴒꜜᴠᴢᴟᴒͼԜᴐᴐᴢᴟԜᴐᴦͼԜꜜᴑͼᴐꜝꜜᴠ꞉ᴠᴡᴒꜜᴐᴦ᷅ͼⱬᴑ꞉ᴡͼᴐⱳᴒᴐꞋͼꜞᴟꜝⱲᴟԜꜛᴠԓͼꜝᴡⱳᴒᴟͼⱱꜝᴟꜛᴠͼꜝⱱͼᴒꞌᴒᴐᴡᴟꜝꜜ꞉ᴐͼᴣԜꞌ꞉ᴑԜᴡ꞉ꜝꜜԓͼ
ꜛԜꜜᴢԜꞌͼꞌ꞉ᴠᴡ꞉ꜜⱲᴠͼԜꜜᴑͼԜͼꜟᴢᴒᴟᴦͼꜞᴟꜝᴐᴒᴠᴠͼᴤ꞉ꞌꞌͼԝᴒͼᴒᴥᴒᴐᴢᴡᴒᴑͼᴡꜝͼᴣᴒᴟ꞉ⱱᴦͼᴡⱳᴒͼԜᴐᴐᴢᴟԜᴐᴦͼꜝⱱͼᴡⱳᴒͼᴑԜᴡԜԝԜᴠᴒ᷅ͼᴁⱳᴒͼ
ⱬⱫⱪͼᴠᴦᴠᴡᴒꜛͼᴤ꞉ꞌꞌͼꜛԜ꞉ꜜᴡԜ꞉ꜜͼԜͼⱱᴢꞌꞌͼԜᴢᴑ꞉ᴡͼᴡᴟԜ꞉ꞌͼꜝⱱͼᴒꞌᴒᴐᴡᴟꜝꜜ꞉ᴐͼᴑԜᴡԜͼᴐⱳԜꜜⱲᴒᴠ᷅ͼⱨᴐᴐᴒᴠᴠͼᴡꜝͼԜꞌꞌͼᴠꜝᴢᴟᴐᴒͼ
ᴑꜝᴐᴢꜛᴒꜜᴡԜᴡ꞉ꜝꜜͼᴤ꞉ꞌꞌͼԝᴒͼꜛԜᴑᴒͼԜᴣԜ꞉ꞌԜԝꞌᴒͼⱱꜝᴟͼꜛꜝꜜ꞉ᴡꜝᴟ꞉ꜜⱲͼԜꜜᴑͼԜᴢᴑ꞉ᴡͼꜞᴢᴟꜞꜝᴠᴒᴠ᷅
10.12 Data Handling Considerations
ⱫԜᴡԜͼᴡⱳԜᴡͼꜛԜᴦͼꜞꜝᴡᴒꜜᴡ꞉Ԝꞌꞌᴦͼᴢꜜԝꞌ꞉ꜜᴑͼᴡⱳᴒͼᴡᴟᴒԜᴡꜛᴒꜜᴡͼԜᴠᴠ꞉Ⱳꜜꜛᴒꜜᴡͼӿ꞉᷅ᴒ᷅ԓͼ꞉ꜜᴣᴒᴠᴡ꞉ⱲԜᴡ꞉ꜝꜜԜꞌͼꜞᴟꜝᴑᴢᴐᴡͼᴠᴒᴟᴢꜛͼ
ᴐꜝꜜᴐᴒꜜᴡᴟԜᴡ꞉ꜝꜜᴠԓͼᴡᴟᴒԜᴡꜛᴒꜜᴡͼԜꞌꞌꜝᴐԜᴡ꞉ꜝꜜԓͼԜꜜᴑͼ꞉ꜜᴣᴒᴠᴡ꞉ⱲԜᴡ꞉ꜝꜜԜꞌͼꜞᴟꜝᴑᴢᴐᴡͼꜞᴟᴒꜞԜᴟԜᴡ꞉ꜝꜜ᷆ԜᴐᴐꜝᴢꜜᴡԜԝ꞉ꞌ꞉ᴡᴦͼᴑԜᴡԜԐͼ
ᴤ꞉ꞌꞌͼԝᴒͼⱳԜꜜᴑꞌᴒᴑͼᴤ꞉ᴡⱳͼᴠꜞᴒᴐ꞉ԜꞌͼᴐԜᴟᴒͼᴑᴢᴟ꞉ꜜⱲͼᴡⱳᴒͼᴑԜᴡԜͼᴐꞌᴒԜꜜ꞉ꜜⱲͼԜꜜᴑͼᴟᴒᴣ꞉ᴒᴤͼꜞᴟꜝᴐᴒᴠᴠ᷅ͼᴁⱳᴒᴠᴒͼᴑԜᴡԜͼᴤ꞉ꞌꞌͼԝᴒͼ
ⱳԜꜜᴑꞌᴒᴑͼ꞉ꜜͼᴠᴢᴐⱳͼԜͼᴤԜᴦͼᴡⱳԜᴡԓͼꜞᴟ꞉ꜝᴟͼᴡꜝͼᴢꜜԝꞌ꞉ꜜᴑ꞉ꜜⱲԓͼԜꜜᴦͼᴑԜᴡԜͼᴡⱳԜᴡͼꜛԜᴦͼᴢꜜԝꞌ꞉ꜜᴑͼᴠᴡᴢᴑᴦͼᴡᴒԜꜛͼꜞᴒᴟᴠꜝꜜꜜᴒꞌͼ
ᴤ꞉ꞌꞌͼԝᴒͼꜞᴟᴒᴠᴒꜜᴡᴒᴑͼԜᴠͼԝꞌ꞉ꜜᴑᴒᴑͼ꞉ꜜⱱꜝᴟꜛԜᴡ꞉ꜝꜜͼꜝᴟͼꜝᴡⱳᴒᴟᴤ꞉ᴠᴒͼᴤ꞉ꞌꞌͼꜜꜝᴡͼԝᴒͼꜛԜᴑᴒͼԜᴣԜ꞉ꞌԜԝꞌᴒ᷅ͼⱷⱱͼԜꜞꜞꞌ꞉ᴐԜԝꞌᴒԓͼ
ᴢꜜԝꞌ꞉ꜜᴑᴒᴑͼᴑԜᴡԜͼꜛԜᴦͼԝᴒͼꜛԜᴑᴒͼԜᴣԜ꞉ꞌԜԝꞌᴒͼᴡꜝͼꜟᴢԜꞌ꞉ᴡᴦͼԜᴠᴠᴢᴟԜꜜᴐᴒͼᴟᴒꜞᴟᴒᴠᴒꜜᴡԜᴡ꞉ᴣᴒᴠͼⱱꜝᴟͼᴡⱳᴒͼꜞᴢᴟꜞꜝᴠᴒᴠͼꜝⱱͼ
ᴐꜝꜜᴑᴢᴐᴡ꞉ꜜⱲͼ꞉ꜜᴑᴒꜞᴒꜜᴑᴒꜜᴡͼᴑᴟᴢⱲͼԜᴢᴑ꞉ᴡᴠ᷅
10.13 Retention of Data
ⱨꞌꞌͼᴠꜝᴢᴟᴐᴒͼᴑꜝᴐᴢꜛᴒꜜᴡᴠͼӿᴒ᷅Ⱳ᷅ԓͼ꞉ꜜⱱꜝᴟꜛᴒᴑͼᴐꜝꜜᴠᴒꜜᴡͼⱱꜝᴟꜛᴠԓͼꞌԜԝꜝᴟԜᴡꜝᴟᴦͼᴟᴒꜞꜝᴟᴡᴠԓͼꜞᴟꜝⱲᴟᴒᴠᴠͼꜜꜝᴡᴒᴠԓͼꜛᴒᴑ꞉ᴐԜꞌͼ
ⱳ꞉ᴠᴡꜝᴟ꞉ᴒᴠԓͼꜞⱳᴦᴠ꞉ᴐԜꞌͼԜꜜᴑͼᴑ꞉ԜⱲꜜꜝᴠᴡ꞉ᴐͼⱱ꞉ꜜᴑ꞉ꜜⱲᴠԓͼᴑ꞉ԜⱲꜜꜝᴠ꞉ᴠͼԜꜜᴑͼꜞⱳԜᴟꜛԜᴐᴦͼᴟᴒᴐꜝᴟᴑᴠԓͼԜꜜᴑͼⱷꜚ͟ͼ
ᴑ꞉ᴠꜞᴒꜜᴠ꞉ꜜⱲ᷆ᴑ꞉ᴠꜞꜝᴠ꞉ᴡ꞉ꜝꜜͼᴟᴒᴐꜝᴟᴑᴠԐͼᴡⱳԜᴡͼᴠᴢꜞꜞꜝᴟᴡͼᴑԜᴡԜͼ꞉ꜜͼᴡⱳᴒͼᴒⱪϸⱴᴠͼꜝⱱͼᴒԜᴐⱳͼᴠᴡᴢᴑᴦͼᴠᴢԝ꞊ᴒᴐᴡͼꜛᴢᴠᴡͼԝᴒͼ
ᴟᴒᴡԜ꞉ꜜᴒᴑͼ꞉ꜜͼᴡⱳᴒͼⱱ꞉ꞌᴒᴠͼꜝⱱͼᴡⱳᴒͼᴟᴒᴠꜞꜝꜜᴠ꞉ԝꞌᴒͼⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟ᷅
ⱨᴐᴐꜝᴟᴑ꞉ꜜⱲͼᴡꜝͼⱷⱪⱶͼⱲᴢ꞉ᴑᴒꞌ꞉ꜜᴒᴠԓͼᴒᴠᴠᴒꜜᴡ꞉ԜꞌͼᴑꜝᴐᴢꜛᴒꜜᴡᴠͼᴠⱳꜝᴢꞌᴑͼԝᴒͼᴟᴒᴡԜ꞉ꜜᴒᴑͼⱱꜝᴟͼԜͼꜛ꞉ꜜ꞉ꜛᴢꜛͼꜝⱱͼ᷉ᴦᴒԜᴟᴠͼ
ԜⱱᴡᴒᴟͼᴡⱳᴒͼꞌԜᴠᴡͼԜꜞꜞᴟꜝᴣԜꞌͼꜝⱱͼԜͼꜛԜᴟꞋᴒᴡ꞉ꜜⱲͼԜꜞꜞꞌ꞉ᴐԜᴡ꞉ꜝꜜͼ꞉ꜜͼԜꜜͼⱷⱪⱶͼᴟᴒⱲ꞉ꜝꜜͼԜꜜᴑͼᴢꜜᴡ꞉ꞌͼᴡⱳᴒᴟᴒͼԜᴟᴒͼꜜꜝͼꜞᴒꜜᴑ꞉ꜜⱲͼ
ꜝᴟͼᴐꜝꜜᴡᴒꜛꜞꞌԜᴡᴒᴑͼꜛԜᴟꞋᴒᴡ꞉ꜜⱲͼԜꜞꜞꞌ꞉ᴐԜᴡ꞉ꜝꜜᴠͼ꞉ꜜͼԜꜜͼⱷⱪⱶͼᴟᴒⱲ꞉ꜝꜜͼꜝᴟͼԜᴡͼꞌᴒԜᴠᴡͼ᷉ᴦᴒԜᴟᴠͼⱳԜᴣᴒͼᴒꞌԜꜞᴠᴒᴑͼᴠ꞉ꜜᴐᴒͼ
ᴡⱳᴒͼⱱꜝᴟꜛԜꞌͼᴑ꞉ᴠᴐꜝꜜᴡ꞉ꜜᴢԜᴡ꞉ꜝꜜͼꜝⱱͼᴐꞌ꞉ꜜ꞉ᴐԜꞌͼᴑᴒᴣᴒꞌꜝꜞꜛᴒꜜᴡͼꜝⱱͼᴡⱳᴒͼⱷꜚ᷅͟ͼⱶꜝᴤᴒᴣᴒᴟԓͼᴡⱳᴒᴠᴒͼᴑꜝᴐᴢꜛᴒꜜᴡᴠͼ
ᴠⱳꜝᴢꞌᴑͼԝᴒͼᴟᴒᴡԜ꞉ꜜᴒᴑͼⱱꜝᴟͼԜͼꞌꜝꜜⱲᴒᴟͼꜞᴒᴟ꞉ꜝᴑͼ꞉ⱱͼᴟᴒꜟᴢ꞉ᴟᴒᴑͼԝᴦͼᴡⱳᴒͼԜꜞꜞꞌ꞉ᴐԜԝꞌᴒͼꞌᴒⱲԜꞌͼᴟᴒꜟᴢ꞉ᴟᴒꜛᴒꜜᴡᴠ᷅
ⱷⱱͼᴡⱳᴒͼᴟᴒᴠꜞꜝꜜᴠ꞉ԝꞌᴒͼⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟͼᴟᴒᴡ꞉ᴟᴒᴠԓͼᴟᴒꞌꜝᴐԜᴡᴒᴠͼꜝᴟͼⱱꜝᴟͼԜꜜᴦͼꜝᴡⱳᴒᴟͼᴟᴒԜᴠꜝꜜͼᴤ꞉ᴡⱳᴑᴟԜᴤᴠͼⱱᴟꜝꜛͼᴡⱳᴒͼ
ᴟᴒᴠꜞꜝꜜᴠ꞉ԝ꞉ꞌ꞉ᴡᴦͼꜝⱱͼꞋᴒᴒꜞ꞉ꜜⱲͼᴡⱳᴒͼᴠᴡᴢᴑᴦͼᴟᴒᴐꜝᴟᴑᴠԓͼᴐᴢᴠᴡꜝᴑᴦͼꜛᴢᴠᴡͼԝᴒͼᴡᴟԜꜜᴠⱱᴒᴟᴟᴒᴑͼᴡꜝͼԜͼꜞᴒᴟᴠꜝꜜͼᴤⱳꜝͼᴤ꞉ꞌꞌͼ
Ԝᴐᴐᴒꜞᴡͼᴡⱳᴒͼᴟᴒᴠꜞꜝꜜᴠ꞉ԝ꞉ꞌ꞉ᴡᴦ᷅ͼᴁⱳᴒͼᴀꜞꜝꜜᴠꜝᴟͼᴟᴒꜞᴟᴒᴠᴒꜜᴡԜᴡ꞉ᴣᴒͼꜛᴢᴠᴡͼԝᴒͼꜜꜝᴡ꞉ⱱ꞉ᴒᴑͼ꞉ꜜͼᴤᴟ꞉ᴡ꞉ꜜⱲͼꜝⱱͼᴡⱳᴒͼꜜԜꜛᴒͼԜꜜᴑͼ
Ԝᴑᴑᴟᴒᴠᴠͼꜝⱱͼᴡⱳᴒͼꜜᴒᴤͼᴐᴢᴠᴡꜝᴑ꞉Ԝꜜԓͼꜞᴟ꞉ꜝᴟͼᴡꜝͼᴡⱳᴒͼᴡᴟԜꜜᴠⱱᴒᴟ᷅

Ⱬᴅ᷄᷉Ⱡ᷊᷇
ⱪꞌ꞉ꜜ꞉ᴐԜꞌͼᴁᴟ꞉Ԝꞌͼ͟ᴟꜝᴡꜝᴐꜝꞌⱡͼⱫᴅ᷄᷉Ⱡ᷊᷊᷇᷄᷇
ⱨꜛᴒꜜᴑꜛᴒꜜᴡͼ᷊᷅᷇ͼⱴ꞉ꜜԜꞌⱡͼ᷇ⱠͼꜗԜꜜᴢԜᴟᴦ᷉᷇᷈ⅎ
ⱪꜝꜜⱱ꞉ᴑᴒꜜᴡ꞉Ԝꞌ
͟ԜⱲᴒͼⱠ᷇
ⱫᴦԜᴥͼⱪꜝᴟꜞ᷅
10.14 Financial Disclosure
ᴁⱳᴒͼⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟͼ꞉ᴠͼᴟᴒꜟᴢ꞉ᴟᴒᴑͼᴡꜝͼᴑ꞉ᴠᴐꞌꜝᴠᴒͼԜꜜᴦͼⱱ꞉ꜜԜꜜᴐ꞉ԜꞌͼԜᴟᴟԜꜜⱲᴒꜛᴒꜜᴡͼᴑᴢᴟ꞉ꜜⱲͼᴡⱳᴒͼᴠᴡᴢᴑᴦͼԜꜜᴑͼⱱꜝᴟͼ᷈ᴦᴒԜᴟͼ
Ԝⱱᴡᴒᴟԓͼᴤⱳᴒᴟᴒԝᴦͼᴡⱳᴒͼꜝᴢᴡᴐꜝꜛᴒͼꜝⱱͼᴡⱳᴒͼᴠᴡᴢᴑᴦͼᴐꜝᴢꞌᴑͼԝᴒͼ꞉ꜜⱱꞌᴢᴒꜜᴐᴒᴑͼԝᴦͼᴡⱳᴒͼᴣԜꞌᴢᴒͼꜝⱱͼᴡⱳᴒͼᴐꜝꜛꜞᴒꜜᴠԜᴡ꞉ꜝꜜͼⱱꜝᴟͼ
ᴐꜝꜜᴑᴢᴐᴡ꞉ꜜⱲͼᴡⱳᴒͼᴠᴡᴢᴑᴦԓͼꜝᴟͼꜝᴡⱳᴒᴟͼꜞԜᴦꜛᴒꜜᴡᴠͼᴡⱳᴒͼⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟͼᴟᴒᴐᴒ꞉ᴣᴒᴑͼⱱᴟꜝꜛͼᴡⱳᴒͼᴀꜞꜝꜜᴠꜝᴟ᷅ͼᴁⱳᴒͼ
ⱱꜝꞌꞌꜝᴤ꞉ꜜⱲͼ꞉ꜜⱱꜝᴟꜛԜᴡ꞉ꜝꜜͼ꞉ᴠͼᴐꜝꞌꞌᴒᴐᴡᴒᴑⱡͼԜꜜᴦͼᴠ꞉Ⱳꜜ꞉ⱱ꞉ᴐԜꜜᴡͼꜞԜᴦꜛᴒꜜᴡᴠͼⱱᴟꜝꜛͼᴡⱳᴒͼᴀꜞꜝꜜᴠꜝᴟͼꜝᴟͼᴠᴢԝᴠ꞉ᴑ꞉Ԝᴟ꞉ᴒᴠͼ
ᴠᴢᴐⱳͼԜᴠͼԜͼⱲᴟԜꜜᴡͼᴡꜝͼⱱᴢꜜᴑͼꜝꜜⱲꜝ꞉ꜜⱲͼᴟᴒᴠᴒԜᴟᴐⱳԓͼᴐꜝꜛꜞᴒꜜᴠԜᴡ꞉ꜝꜜͼ꞉ꜜͼᴡⱳᴒͼⱱꜝᴟꜛͼꜝⱱͼᴒꜟᴢ꞉ꜞꜛᴒꜜᴡԓͼᴟᴒᴡԜ꞉ꜜᴒᴟͼⱱꜝᴟͼ
ꜝꜜⱲꜝ꞉ꜜⱲͼᴐꜝꜜᴠᴢꞌᴡԜᴡ꞉ꜝꜜͼꜝᴟͼⱳꜝꜜꜝᴟԜᴟ꞉ԜⱢͼԜꜜᴦͼꜞᴟꜝꜞᴟ꞉ᴒᴡԜᴟᴦͼ꞉ꜜᴡᴒᴟᴒᴠᴡͼ꞉ꜜͼ꞉ꜜᴣᴒᴠᴡ꞉ⱲԜᴡ꞉ꜝꜜԜꞌͼꜞᴟꜝᴑᴢᴐᴡⱢԜꜜᴦͼ
ᴠ꞉Ⱳꜜ꞉ⱱ꞉ᴐԜꜜᴡͼᴒꜟᴢ꞉ᴡᴦͼ꞉ꜜᴡᴒᴟᴒᴠᴡͼ꞉ꜜͼᴡⱳᴒͼᴀꜞꜝꜜᴠꜝᴟͼꜝᴟͼᴠᴢԝᴠ꞉ᴑ꞉Ԝᴟ꞉ᴒᴠͼԜᴠͼᴑᴒⱱ꞉ꜜᴒᴑͼ꞉ꜜͼ᷉᷈ͼⱪⱴϸͼ᷿᷾ͼ᷉ӿԝԐͼӿ᷈ⱠⱠ˲Ԑ᷅
10.15 Publication and Disclosure Policy
ⱨꞌꞌͼ꞉ꜜⱱꜝᴟꜛԜᴡ꞉ꜝꜜͼᴐꜝꜜᴐᴒᴟꜜ꞉ꜜⱲͼⱫᴅ᷄᷉Ⱡ᷊᷇ԓͼᴀꜞꜝꜜᴠꜝᴟͼꜝꜞᴒᴟԜᴡ꞉ꜝꜜᴠԓͼꜞԜᴡᴒꜜᴡͼԜꜞꜞꞌ꞉ᴐԜᴡ꞉ꜝꜜᴠԓͼⱱꜝᴟꜛᴢꞌԜᴠԓͼ
ꜛԜꜜᴢⱱԜᴐᴡᴢᴟ꞉ꜜⱲͼꜞᴟꜝᴐᴒᴠᴠᴒᴠԓͼԝԜᴠ꞉ᴐͼᴠᴐ꞉ᴒꜜᴡ꞉ⱱ꞉ᴐͼᴑԜᴡԜԓͼԜꜜᴑͼⱱꜝᴟꜛᴢꞌԜᴡ꞉ꜝꜜͼ꞉ꜜⱱꜝᴟꜛԜᴡ꞉ꜝꜜԓͼᴠᴢꜞꜞꞌ꞉ᴒᴑͼᴡꜝͼᴡⱳᴒͼ
ⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟͼԝᴦͼԜͼᴀꜞꜝꜜᴠꜝᴟͼᴟᴒꜞᴟᴒᴠᴒꜜᴡԜᴡ꞉ᴣᴒͼԜꜜᴑͼꜜꜝᴡͼꜞᴟᴒᴣ꞉ꜝᴢᴠꞌᴦͼꜞᴢԝꞌ꞉ᴠⱳᴒᴑԓͼ꞉ᴠͼᴐꜝꜜᴠ꞉ᴑᴒᴟᴒᴑͼᴐꜝꜜⱱ꞉ᴑᴒꜜᴡ꞉Ԝꞌͼ
ԜꜜᴑͼᴟᴒꜛԜ꞉ꜜᴠͼᴡⱳᴒͼᴠꜝꞌᴒͼꜞᴟꜝꜞᴒᴟᴡᴦͼꜝⱱͼᴡⱳᴒͼᴀꜞꜝꜜᴠꜝᴟ᷅ͼᴁⱳᴒͼⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟͼꜛᴢᴠᴡͼԜⱲᴟᴒᴒͼᴡꜝͼᴢᴠᴒͼᴡⱳ꞉ᴠͼ꞉ꜜⱱꜝᴟꜛԜᴡ꞉ꜝꜜͼ
ꜝꜜꞌᴦͼᴡꜝͼԜᴐᴐꜝꜛꜞꞌ꞉ᴠⱳͼᴡⱳ꞉ᴠͼᴠᴡᴢᴑᴦԓͼԜꜜᴑͼꜛᴢᴠᴡͼꜜꜝᴡͼᴢᴠᴒͼ꞉ᴡͼⱱꜝᴟͼꜝᴡⱳᴒᴟͼꜞᴢᴟꜞꜝᴠᴒᴠͼᴤ꞉ᴡⱳꜝᴢᴡͼᴡⱳᴒͼᴀꜞꜝꜜᴠꜝᴟᶳᴠͼ
ԜᴑᴣԜꜜᴐᴒᴑͼᴤᴟ꞉ᴡᴡᴒꜜͼᴐꜝꜜᴠᴒꜜᴡ᷅ͼⱨͼᴑᴒᴠᴐᴟ꞉ꜞᴡ꞉ꜝꜜͼꜝⱱͼᴡⱳ꞉ᴠͼᴐꞌ꞉ꜜ꞉ᴐԜꞌͼᴠᴡᴢᴑᴦͼꜛԜᴦͼԜꞌᴠꜝͼԝᴒͼԜᴣԜ꞉ꞌԜԝꞌᴒͼꜝꜜͼꜝᴡⱳᴒᴟͼ
ᴒᴥᴡᴒᴟꜜԜꞌꞌᴦͼⱱԜᴐ꞉ꜜⱲͼꜞᴢԝꞌ꞉ᴐͼᴤᴒԝᴠ꞉ᴡᴒᴠͼԜꜜᴑͼᴟᴒⱲ꞉ᴠᴡᴟ꞉ᴒᴠ᷅ͼⱨͼᴠᴢꜛꜛԜᴟᴦͼꜝⱱͼᴡⱳᴒͼᴠᴡᴢᴑᴦͼᴟᴒᴠᴢꞌᴡᴠͼꜛԜᴦͼԝᴒͼ
ꜞꜝᴡᴒꜜᴡ꞉Ԝꞌꞌᴦͼᴑ꞉ᴠᴐꞌꜝᴠᴒᴑͼԜᴠͼꜞᴒᴟͼꞌꜝᴐԜꞌͼԜꜜᴑͼᴐꜝᴢꜜᴡᴟᴦͼᴠꜞᴒᴐ꞉ⱱ꞉ᴐͼᴟᴒꜟᴢ꞉ᴟᴒꜛᴒꜜᴡᴠ᷅
ᴁⱳᴒͼ꞉ꜜⱱꜝᴟꜛԜᴡ꞉ꜝꜜͼᴑᴒᴣᴒꞌꜝꜞᴒᴑͼ꞉ꜜͼᴡⱳ꞉ᴠͼᴠᴡᴢᴑᴦͼᴤ꞉ꞌꞌͼԝᴒͼᴢᴠᴒᴑͼԝᴦͼᴡⱳᴒͼᴀꜞꜝꜜᴠꜝᴟͼ꞉ꜜͼᴐꜝꜜꜜᴒᴐᴡ꞉ꜝꜜͼᴤ꞉ᴡⱳͼᴡⱳᴒͼ
ᴐꜝꜜᴡ꞉ꜜᴢᴒᴑͼᴑᴒᴣᴒꞌꜝꜞꜛᴒꜜᴡͼꜝⱱͼⱫᴅ᷄᷉Ⱡ᷊᷇ͼԜꜜᴑͼᴡⱳᴢᴠͼꜛԜᴦͼԝᴒͼᴑ꞉ᴠᴐꞌꜝᴠᴒᴑͼԜᴠͼᴟᴒꜟᴢ꞉ᴟᴒᴑͼᴡꜝͼꜝᴡⱳᴒᴟͼᴐꞌ꞉ꜜ꞉ᴐԜꞌͼ
ⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟᴠͼꜝᴟͼⱲꜝᴣᴒᴟꜜꜛᴒꜜᴡͼᴟᴒⱲᴢꞌԜᴡꜝᴟᴦͼԜⱲᴒꜜᴐ꞉ᴒᴠ᷅ͼᴁꜝͼꜞᴒᴟꜛ꞉ᴡͼᴡⱳᴒͼ꞉ꜜⱱꜝᴟꜛԜᴡ꞉ꜝꜜͼᴑᴒᴟ꞉ᴣᴒᴑͼⱱᴟꜝꜛͼᴡⱳᴒͼ
ᴐꞌ꞉ꜜ꞉ᴐԜꞌͼᴠᴡᴢᴑ꞉ᴒᴠͼᴡꜝͼԝᴒͼᴢᴠᴒᴑԓͼᴡⱳᴒⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟͼ꞉ᴠͼꜝԝꞌ꞉ⱲԜᴡᴒᴑͼᴡꜝͼꜞᴟꜝᴣ꞉ᴑᴒͼᴡⱳᴒͼᴀꜞꜝꜜᴠꜝᴟͼᴤ꞉ᴡⱳͼԜꞌꞌͼᴑԜᴡԜͼ
ꜝԝᴡԜ꞉ꜜᴒᴑͼ꞉ꜜͼᴡⱳᴒͼᴠᴡᴢᴑᴦ᷅

Ⱬᴅ᷄᷉Ⱡ᷊᷇
ⱪꞌ꞉ꜜ꞉ᴐԜꞌͼᴁᴟ꞉Ԝꞌͼ͟ᴟꜝᴡꜝᴐꜝꞌⱡͼⱫᴅ᷄᷉Ⱡ᷊᷊᷇᷄᷇
ⱨꜛᴒꜜᴑꜛᴒꜜᴡͼ᷊᷅᷇ͼⱴ꞉ꜜԜꞌⱡͼ᷇ⱠͼꜗԜꜜᴢԜᴟᴦ᷉᷇᷈ⅎ
ⱪꜝꜜⱱ꞉ᴑᴒꜜᴡ꞉Ԝꞌ
͟ԜⱲᴒͼⱠ᷈
ⱫᴦԜᴥͼⱪꜝᴟꜞ᷅
11 REFERENCE LIST
ⱩᴒꜜꜜᴒᴡᴡͼⱵԓͼⱪᴟԜ꞉Ⱳͼᴁ᷅ͼⱶᴒᴟᴒᴑ꞉ᴡԜᴟᴦͼԜꜜⱲ꞉ꜝᴒᴑᴒꜛԜͼᴤ꞉ᴡⱳͼԜͼⱱꜝᴐᴢᴠͼꜝꜜͼᴡⱳᴒͼᴐⱳ꞉ꞌᴑ᷅ͼⱨꞌꞌᴒᴟⱲᴦͼⱨᴠᴡⱳꜛԜͼ͟ᴟꜝᴐ᷅ͼ
᷿᷉᷇᷈Ɫ᷊⅍ӿ᷈Ԑⱡⅎ᷊᷇᷄᷅
ⱩꜝᴟꞋͼꜘԓͼⱶԜᴟᴑᴡͼꜗԓͼᴀᴐⱳ꞉ᴐꞋᴒᴡԜꜜᴧͼꜘ᷄ⱶԓͼϸᴒᴠᴠᴒꞌͼ꜠᷅ͼⱪꞌ꞉ꜜ꞉ᴐԜꞌͼᴠᴡᴢᴑ꞉ᴒᴠͼꜝⱱͼᴠᴢᴑᴑᴒꜜͼᴢꜞꜞᴒᴟͼԜ꞉ᴟᴤԜᴦͼꜝԝᴠᴡᴟᴢᴐᴡ꞉ꜝꜜͼ
꞉ꜜͼꜞԜᴡ꞉ᴒꜜᴡᴠͼᴤ꞉ᴡⱳͼⱳᴒᴟᴒᴑ꞉ᴡԜᴟᴦͼԜꜜⱲ꞉ꜝᴒᴑᴒꜛԜͼᴑᴢᴒͼᴡꜝͼⱪ᷈ͼᴒᴠᴡᴒᴟԜᴠᴒͼ꞉ꜜⱳ꞉ԝ꞉ᴡꜝᴟͼᴑᴒⱱ꞉ᴐ꞉ᴒꜜᴐᴦ᷅ͼⱨᴟᴐⱳͼⱷꜜᴡͼꜚᴒᴑ᷅ͼ
᷊᷉᷇᷇Ɫ᷈⅍᷊ⱡ᷈᷉᷉Ⱡ᷊᷿᷄᷈᷉᷅
ⱩꜝᴟꞋͼꜘԓͼⱶԜᴟᴑᴡͼꜗԓͼᴄ꞉ᴡᴧꞋᴒͼⱵ᷅ͼⱴԜᴡԜꞌͼꞌԜᴟᴦꜜⱲᴒԜꞌͼԜᴡᴡԜᴐꞋᴠͼԜꜜᴑͼꜛꜝᴟᴡԜꞌ꞉ᴡᴦͼ꞉ꜜͼⱳᴒᴟᴒᴑ꞉ᴡԜᴟᴦͼԜꜜⱲ꞉ꜝᴒᴑᴒꜛԜͼᴑᴢᴒͼᴡꜝͼ
ⱪ᷈᷄ⱷ꜠ⱶͼᴑᴒⱱ꞉ᴐ꞉ᴒꜜᴐᴦ᷅ͼꜗͼⱨꞌꞌᴒᴟⱲᴦͼⱪꞌ꞉ꜜͼⱷꜛꜛᴢꜜꜝꞌ᷅ͼ᷉᷇᷈᷉Ɫ᷊᷈᷇ӿ᷊Ԑⱡ⅍Ⱡ᷉᷄ⅎ᷅
ⱩꜝᴟꞋͼꜘԓͼꜚᴒꜜⱲͼⱵԓͼᴀᴡԜᴢԝԜᴐⱳͼ͟ԓͼⱶԜᴟᴑᴡͼꜗ᷅ͼⱶᴒᴟᴒᴑ꞉ᴡԜᴟᴦͼԜꜜⱲ꞉ꜝᴒᴑᴒꜛԜⱡͼ꜠ᴒᴤͼⱱ꞉ꜜᴑ꞉ꜜⱲᴠͼᴐꜝꜜᴐᴒᴟꜜ꞉ꜜⱲͼ
ᴠᴦꜛꜞᴡꜝꜛᴠԓͼԜⱱⱱᴒᴐᴡᴒᴑͼꜝᴟⱲԜꜜᴠԓͼԜꜜᴑͼᴐꜝᴢᴟᴠᴒ᷅ͼⱨꜛͼꜗͼꜚᴒᴑ᷅ͼ᷉᷇᷇⅍Ɫ᷈᷈Ⱡӿ᷊Ԑⱡ᷉⅍ⅎ᷄᷉ⅎ᷾᷅
ⱩꜝᴟꞋͼꜘԓͼᴀ꞉ᴒᴑꞌᴒᴐꞋ꞉ͼꜘԓͼⱩꜝᴠᴐⱳͼᴀԓͼᴀᴐⱳꜝꜞⱱͼϸⱬԓͼꜘᴟᴒᴢᴧͼᴄ᷅ͼⱨᴠꜞⱳᴦᴥ꞉Ԝᴡ꞉ꜝꜜͼԝᴦͼꞌԜᴟᴦꜜⱲᴒԜꞌͼᴒᴑᴒꜛԜͼ꞉ꜜͼ
ꜞԜᴡ꞉ᴒꜜᴡᴠͼᴤ꞉ᴡⱳͼⱳᴒᴟᴒᴑ꞉ᴡԜᴟᴦͼԜꜜⱲ꞉ꜝᴒᴑᴒꜛԜ᷅ͼꜚԜᴦꜝͼⱪꞌ꞉ꜜͼ͟ᴟꜝᴐ᷅ͼ᷉᷇᷇᷇Ɫⅎ᷿ӿ᷾Ԑⱡ᷊᷾Ⱡ᷿᷄᷾᷅
ⱩᴦⱲᴢꜛͼⱨ᷅ͼⱶᴒᴟᴒᴑ꞉ᴡԜᴟᴦͼԜꜜⱲ꞉ꜝ᷄ꜝᴒᴑᴒꜛԜͼ꞉ꜜͼⱫᴒꜜꜛԜᴟꞋⱡͼԜͼꜜԜᴡ꞉ꜝꜜᴤ꞉ᴑᴒͼᴠᴢᴟᴣᴒᴦ᷅ͼⱩᴟͼꜗͼⱫᴒᴟꜛԜᴡꜝꞌ᷅ͼ
᷉᷇᷇ⱠⱢ᷈⅍᷈ӿ᷿Ԑⱡ᷿᷊᷈᷈᷄˲᷅
ⱪ꞉ᴐԜᴟᴑ꞉ͼꜚԓͼⱩꜝᴟꞋͼꜘԓͼⱪԜԝԜꞌꞌᴒᴟꜝͼᴁԓͼⱪᴟԜ꞉Ⱳͼᴁԓͼꜙ꞉ͼⱶⱶԓͼꜙꜝꜜⱲⱳᴢᴟᴠᴡͼⱶԓͼᴒᴡͼԜꞌ᷅ͼⱬᴣ꞉ᴑᴒꜜᴐᴒ᷄ԝԜᴠᴒᴑͼ
ᴟᴒᴐꜝꜛꜛᴒꜜᴑԜᴡ꞉ꜝꜜᴠͼⱱꜝᴟͼᴡⱳᴒͼᴡⱳᴒᴟԜꜞᴒᴢᴡ꞉ᴐͼꜛԜꜜԜⱲᴒꜛᴒꜜᴡͼꜝⱱͼԜꜜⱲ꞉ꜝᴒᴑᴒꜛԜͼꜝᴤ꞉ꜜⱲͼᴡꜝͼⱳᴒᴟᴒᴑ꞉ᴡԜᴟᴦͼⱪ᷈ͼ
꞉ꜜⱳ꞉ԝ꞉ᴡꜝᴟͼᴑᴒⱱ꞉ᴐ꞉ᴒꜜᴐᴦⱡͼᴐꜝꜜᴠᴒꜜᴠᴢᴠͼᴟᴒꜞꜝᴟᴡͼꜝⱱͼԜꜜͼⱷꜜᴡᴒᴟꜜԜᴡ꞉ꜝꜜԜꞌͼᴄꜝᴟꞋ꞉ꜜⱲͼⱵᴟꜝᴢꜞ᷅ͼⱨꞌꞌᴒᴟⱲᴦ᷅ͼ
᷉᷇᷈᷉Ɫ⅍ⅎӿ᷉Ԑⱡ᷈᷾ⅎ᷿᷄ⅎ᷅
ⱪᴟԜ꞉Ⱳͼᴁԓͼ͟ᴢᴟᴠᴢꜜͼⱬⱨԓͼⱩꜝᴟꞋͼꜘԓͼⱩꜝᴤᴒꜜͼᴁԓͼⱩꜝᴦᴠᴒꜜͼⱶԓͼⱴԜᴟꞋԜᴠͼⱶԓͼᴒᴡͼԜꞌ᷅ͼᴄⱨ꜡ͼⱵᴢ꞉ᴑᴒꞌ꞉ꜜᴒͼⱱꜝᴟͼᴡⱳᴒͼ
ꜚԜꜜԜⱲᴒꜛᴒꜜᴡͼꜝⱱͼⱶᴒᴟᴒᴑ꞉ᴡԜᴟᴦͼⱨꜜⱲ꞉ꜝᴒᴑᴒꜛԜ᷅ͼᴄꜝᴟꞌᴑͼⱨꞌꞌᴒᴟⱲᴦͼ꜡ᴟⱲԜꜜͼꜗ᷅ͼ᷉᷇᷈᷉Ɫ᷿ӿ᷈᷉Ԑⱡ᷈˲᷉᷄᷈ⱠⱠ᷅
ⱫԜᴣ꞉ᴠͼⱨⱬԓͼ᷊ᴟᴑ᷅ͼꜚᴒᴐⱳԜꜜ꞉ᴠꜛͼꜝⱱͼԜꜜⱲ꞉ꜝᴒᴑᴒꜛԜͼ꞉ꜜͼⱱ꞉ᴟᴠᴡͼᴐꜝꜛꜞꞌᴒꜛᴒꜜᴡͼᴐꜝꜛꜞꜝꜜᴒꜜᴡͼ꞉ꜜⱳ꞉ԝ꞉ᴡꜝᴟͼᴑᴒⱱ꞉ᴐ꞉ᴒꜜᴐᴦ᷅ͼ
ⱷꜛꜛᴢꜜꜝꞌͼⱨꞌꞌᴒᴟⱲᴦͼⱪꞌ꞉ꜜͼ꜠ꜝᴟᴡⱳͼⱨꜛ᷅ͼ᷉᷇᷇⅍Ɫ᷉⅍ӿ᷾Ԑⱡ⅍᷊᷊᷿᷄᷈᷅
ⱴԜᴟꞋԜᴠͼⱶ᷅ͼ͟ᴒᴑ꞉Ԝᴡᴟ꞉ᴐͼⱳᴒᴟᴒᴑ꞉ᴡԜᴟᴦͼԜꜜⱲ꞉ꜝᴒᴑᴒꜛԜͼᴑᴢᴒͼᴡꜝͼⱪ᷈᷄꞉ꜜⱳ꞉ԝ꞉ᴡꜝᴟͼᴑᴒⱱ꞉ᴐ꞉ᴒꜜᴐᴦ᷅ͼⱨꞌꞌᴒᴟⱲᴦͼⱨᴠᴡⱳꜛԜͼⱪꞌ꞉ꜜͼ
ⱷꜛꜛᴢꜜꜝꞌ᷅ͼ᷉᷇᷈᷇Ɫ⅍ӿ᷈Ԑⱡ᷈˲᷅
Ⱶꜝᴟ꞉ꜜⱲͼⱶⱫԓͼⱩꜝᴟꞋͼꜘԓͼᴀꜞԜᴡⱳͼ͟ꜗԓͼⱩԜᴢᴒᴟͼϸԓͼᴇ꞉ᴒꜛᴒᴟͼⱨԓͼⱶ꞉ꜜᴡꜜᴒᴟͼⱶԓͼᴒᴡͼԜꞌ᷅ͼᴈⱶᴒᴟᴒᴑ꞉ᴡԜᴟᴦͼԜꜜⱲ꞉ꜝᴒᴑᴒꜛԜͼ꞉ꜜͼ
ᴡⱳᴒͼⱵᴒᴟꜛԜꜜ᷄ᴠꜞᴒԜꞋ꞉ꜜⱲͼᴟᴒⱲ꞉ꜝꜜᴊ᷅ͼⱶԜᴢᴡԜᴟᴧᴡ᷅ͼ᷈ⱠⱠ˲Ɫ᷾Ⱡӿ᷉Ԑⱡ᷈᷈᷾᷄᷉᷉᷅
ꜘⱨꜙⱩⱷᴁ꜡ϸᶇͼӿᴒᴐԜꞌꞌԜꜜᴡ꞉ᴑᴒԐͼᴈꜞԜᴐꞋԜⱲᴒͼ꞉ꜜᴠᴒᴟᴡᴊͼⱩᴢᴟꞌ꞉ꜜⱲᴡꜝꜜԓͼꜚⱨⱡͼⱫᴦԜᴥͼⱪꜝᴟꜞ᷅Ɫͼ᷿᷉᷇᷈᷅
ꜘԜꜞꞌԜꜜͼⱨ͟ԓͼꜗꜝᴠᴒꜞⱳͼꜘ᷅ͼᴁⱳᴒͼԝᴟԜᴑᴦꞋ꞉ꜜ꞉ꜜ᷄ⱱꜝᴟꜛ꞉ꜜⱲͼᴐԜᴠᴐԜᴑᴒͼԜꜜᴑͼ꞉ᴡᴠͼᴟꜝꞌᴒͼ꞉ꜜͼⱳᴒᴟᴒᴑ꞉ᴡԜᴟᴦͼԜꜜⱲ꞉ꜝᴒᴑᴒꜛԜ᷅ͼ
ⱨꜜꜜͼⱨꞌꞌᴒᴟⱲᴦͼⱨᴠᴡⱳꜛԜͼⱷꜛꜛᴢꜜꜝꞌ᷅ͼ᷉᷇᷈᷇Ɫ᷈᷇᷾ӿ᷊Ԑⱡ᷈Ⱡ᷊᷄᷉᷇᷾᷅

Ⱬᴅ᷄᷉Ⱡ᷊᷇
ⱪꞌ꞉ꜜ꞉ᴐԜꞌͼᴁᴟ꞉Ԝꞌͼ͟ᴟꜝᴡꜝᴐꜝꞌⱡͼⱫᴅ᷄᷉Ⱡ᷊᷊᷇᷄᷇
ⱨꜛᴒꜜᴑꜛᴒꜜᴡͼ᷊᷅᷇ͼⱴ꞉ꜜԜꞌⱡͼ᷇ⱠͼꜗԜꜜᴢԜᴟᴦ᷉᷇᷈ⅎ
ⱪꜝꜜⱱ꞉ᴑᴒꜜᴡ꞉Ԝꞌ
͟ԜⱲᴒͼⱠ᷉
ⱫᴦԜᴥͼⱪꜝᴟꜞ᷅
ꜘᴒꜜꜜ꞉ᴠᴡꜝꜜͼꜗⱨԓͼⱴԜᴢᴐᴒᴡᴡᴒͼϸϸԓͼꜚԜᴟᴡ꞉ꞋͼⱫԓͼⱪꜝꜛᴒԜᴢͼᴀϸԓͼꜙ꞉ꜜᴑԝᴒᴟⱲͼⱨ͟ԓͼꜘꜝꜞԜᴐᴧͼꜘꜗԓͼᴒᴡͼԜꞌ᷅ͼⱷꜜⱳ꞉ԝ꞉ᴡ꞉ꜝꜜͼꜝⱱͼ
ꜞꞌԜᴠꜛԜͼꞋԜꞌꞌ꞉Ꞌᴟᴒ꞉ꜜͼԝᴦͼԜͼⱳ꞉Ⱳⱳꞌᴦͼᴠꜞᴒᴐ꞉ⱱ꞉ᴐͼԜᴐᴡ꞉ᴣᴒͼᴠ꞉ᴡᴒͼԝꞌꜝᴐꞋ꞉ꜜⱲͼԜꜜᴡ꞉ԝꜝᴑᴦ᷅ͼꜗͼⱩ꞉ꜝꞌͼⱪⱳᴒꜛ᷅ͼ
᷉᷇᷈᷾Ɫ᷉˲Ⱡӿ᷊᷾Ԑⱡ᷊᷿᷉Ⱡ⅍᷄⅍᷇˲᷅
ꜙᴒ꞉ͼᴄᴁԓͼᴀⱳᴦᴢᴟͼᴀⱫԓͼⱶᴢԜꜜⱲͼꜙⱶԓͼꜘԜꜝͼᴆⱶԓͼꜙꜝͼⱪᴆ᷅ͼᴁᴦꜞᴒͼⱷͼⱳᴒᴟᴒᴑ꞉ᴡԜᴟᴦͼԜꜜⱲ꞉ꜝᴒᴑᴒꜛԜͼ꞉ꜜͼᴁԜ꞉ᴤԜꜜͼ᷄᷄
ᴐꞌ꞉ꜜ꞉ᴐԜꞌԓͼԝ꞉ꜝꞌꜝⱲ꞉ᴐԜꞌͼⱱᴒԜᴡᴢᴟᴒᴠͼԜꜜᴑͼⱲᴒꜜᴒᴡ꞉ᴐͼᴠᴡᴢᴑᴦ᷅ͼⱨᴠ꞉Ԝꜜͼ͟ԜᴐͼꜗͼⱨꞌꞌᴒᴟⱲᴦͼⱷꜛꜛᴢꜜꜝꞌ᷅ͼ᷉᷇᷈᷈Ɫ᷉Ⱡӿ᷾Ԑⱡ᷊᷉ⅎ᷊᷄᷈᷅
꜠ꜝᴟᴑᴒꜜⱱᴒꞌᴡͼ͟ԓͼⱫԜᴤᴠꜝꜜͼᴀԓͼᴄԜⱳꞌⱲᴟᴒꜜͼⱪⱴԓͼꜙ꞉ꜜᴑⱱꜝᴟᴠͼⱨԓͼꜚԜꞌꞌԝᴟ꞉ᴠͼꜙԓͼⱩ꞊ꜝᴟꞋԜꜜᴑᴒᴟͼꜗ᷅ͼϷᴢԜꜜᴡ꞉ⱱᴦ꞉ꜜⱲͼᴡⱳᴒͼ
ԝᴢᴟᴑᴒꜜͼꜝⱱͼᴑ꞉ᴠᴒԜᴠᴒͼԜꜜᴑͼꜞᴒᴟᴐᴒ꞉ᴣᴒᴑͼⱳᴒԜꞌᴡⱳͼᴠᴡԜᴡᴒͼ꞉ꜜͼꜞԜᴡ꞉ᴒꜜᴡᴠͼᴤ꞉ᴡⱳͼⱳᴒᴟᴒᴑ꞉ᴡԜᴟᴦͼԜꜜⱲ꞉ꜝᴒᴑᴒꜛԜͼ꞉ꜜͼᴀᴤᴒᴑᴒꜜ᷅ͼ
ⱨꞌꞌᴒᴟⱲᴦͼⱨᴠᴡⱳꜛԜͼ͟ᴟꜝᴐ᷅ͼ᷉᷇᷈᷾Ɫ᷊᷿ӿ᷉Ԑⱡ᷈˲᷿᷄Ⱡ᷇᷅
ϸᴒꜜꜜᴒͼᴁԓͼⱵᴟᴢԝᴒᴟͼⱨ᷅ͼ͟ꞌԜᴠꜛԜͼꞋԜꞌꞌ꞉Ꞌᴟᴒ꞉ꜜⱡͼꜜꜝᴣᴒꞌͼⱱᴢꜜᴐᴡ꞉ꜝꜜᴠͼⱱꜝᴟͼԜꜜͼꜝꞌᴑͼꜞᴟꜝᴡᴒԜᴠᴒ᷅ͼᴁⱳᴟꜝꜛԝͼⱶԜᴒꜛꜝᴠᴡ᷅ͼ
᷉᷇᷈᷉Ɫ᷈᷇ⅎӿ⅍Ԑⱡ᷊᷈᷇᷈᷉᷄᷅
ϸꜝᴐⱳᴒͼ꜡ԓͼⱩꞌԜꜜᴐⱳͼⱨԓͼⱪԜԝԜꞌꞌᴒᴟꜝͼᴁԓͼᴀԜᴠᴡᴟᴒͼ꜠ԓͼⱪԜꞌꞌᴒ꞊ꜝͼⱫԓͼꜙꜝꜞᴒᴧ᷄ᴁᴟԜᴠᴐԜᴠԜͼꜚ᷅ͼⱶᴒᴟᴒᴑ꞉ᴡԜᴟᴦͼ
ԜꜜⱲ꞉ꜝᴒᴑᴒꜛԜͼᴑᴢᴒͼᴡꜝͼⱪ᷈ͼ꞉ꜜⱳ꞉ԝ꞉ᴡꜝᴟͼᴑᴒⱱ꞉ᴐ꞉ᴒꜜᴐᴦⱡͼꜞԜᴡ꞉ᴒꜜᴡͼᴟᴒⱲ꞉ᴠᴡᴟᴦͼԜꜜᴑͼԜꜞꜞᴟꜝԜᴐⱳͼᴡꜝͼᴡⱳᴒͼꜞᴟᴒᴣԜꞌᴒꜜᴐᴒͼ꞉ꜜͼ
ᴀꜞԜ꞉ꜜ᷅ͼⱨꜜꜜͼⱨꞌꞌᴒᴟⱲᴦͼⱨᴠᴡⱳꜛԜͼⱷꜛꜛᴢꜜꜝꞌ᷅ͼ᷿᷉᷇᷇ⱢⱠ᷾ӿ᷾Ԑⱡ᷾Ⱡ˲᷿᷊᷄᷇᷅
ᴇᴢᴟԜᴤͼⱩꜙ᷅ͼⱪꞌ꞉ꜜ꞉ᴐԜꞌͼꜞᴟԜᴐᴡ꞉ᴐᴒ᷅ͼⱶᴒᴟᴒᴑ꞉ᴡԜᴟᴦͼԜꜜⱲ꞉ꜝᴒᴑᴒꜛԜ᷅ͼ꜠ͼⱬꜜⱲꞌͼꜗͼꜚᴒᴑ᷅ͼ᷉᷇᷇˲Ɫ᷊᷿Ⱡӿ᷈᷇Ԑⱡ᷈᷇᷉ⅎ᷊᷄⅍᷅
ᴇᴢᴟԜᴤͼⱩꜙԓͼⱩԜꜜᴒᴟ꞊꞉ͼⱨԓͼⱩᴒᴟꜜᴠᴡᴒ꞉ꜜͼꜗⱨԓͼⱩᴢᴠᴠᴒͼ͟ꜗԓͼⱪⱳᴟ꞉ᴠᴡ꞉ԜꜜᴠᴒꜜͼᴀⱪԓͼⱫԜᴣ꞉ᴠ᷄ꜙꜝᴟᴡꜝꜜͼꜚԓͼᴒᴡͼԜꞌ᷅ͼᴂᴀͼ
ⱶᴒᴟᴒᴑ꞉ᴡԜᴟᴦͼⱨꜜⱲ꞉ꜝᴒᴑᴒꜛԜͼⱨᴠᴠꜝᴐ꞉Ԝᴡ꞉ꜝꜜͼꜚᴒᴑ꞉ᴐԜꞌͼⱨᴑᴣ꞉ᴠꜝᴟᴦͼⱩꜝԜᴟᴑͼ᷊᷉᷇᷈ͼϸᴒᴐꜝꜛꜛᴒꜜᴑԜᴡ꞉ꜝꜜᴠͼⱱꜝᴟͼᴡⱳᴒͼ
ꜚԜꜜԜⱲᴒꜛᴒꜜᴡͼꜝⱱͼⱶᴒᴟᴒᴑ꞉ᴡԜᴟᴦͼⱨꜜⱲ꞉ꜝᴒᴑᴒꜛԜͼⱫᴢᴒͼᴡꜝͼⱪ᷈ͼⱷꜜⱳ꞉ԝ꞉ᴡꜝᴟͼⱫᴒⱱ꞉ᴐ꞉ᴒꜜᴐᴦ᷅ͼꜗͼⱨꞌꞌᴒᴟⱲᴦͼⱪꞌ꞉ꜜͼ
ⱷꜛꜛᴢꜜꜝꞌͼ͟ᴟԜᴐᴡ᷅ͼ᷊᷉᷇᷈Ɫ᷈ӿ᷿Ԑⱡ᷿᷾˲᷄⅍ⅎ᷅
ᴇᴢᴟԜᴤͼⱩꜙԓͼⱩᴒᴟꜜᴠᴡᴒ꞉ꜜͼꜗⱨԓͼꜙԜꜜⱲͼⱫꜚԓͼⱪᴟԜ꞉ⱲͼᴁԓͼⱫᴟᴒᴦⱱᴢᴠͼⱫԓͼⱶᴠ꞉ᴒⱳͼⱴԓͼᴒᴡͼԜꞌ᷅ͼⱨͼⱱꜝᴐᴢᴠᴒᴑͼꜞԜᴟԜꜛᴒᴡᴒᴟͼ
ᴢꜞᴑԜᴡᴒⱡͼⱶᴒᴟᴒᴑ꞉ᴡԜᴟᴦͼԜꜜⱲ꞉ꜝᴒᴑᴒꜛԜԓͼԜᴐꜟᴢ꞉ᴟᴒᴑͼⱪ᷈ͼ꞉ꜜⱳ꞉ԝ꞉ᴡꜝᴟͼᴑᴒⱱ꞉ᴐ꞉ᴒꜜᴐᴦԓͼԜꜜᴑͼԜꜜⱲ꞉ꜝᴡᴒꜜᴠ꞉ꜜ᷄ᴐꜝꜜᴣᴒᴟᴡ꞉ꜜⱲͼ
ᴒꜜᴧᴦꜛᴒͼ꞉ꜜⱳ꞉ԝ꞉ᴡꜝᴟ᷄Ԝᴠᴠꜝᴐ꞉ԜᴡᴒᴑͼԜꜜⱲ꞉ꜝᴒᴑᴒꜛԜ᷅ͼꜗͼⱨꞌꞌᴒᴟⱲᴦͼⱪꞌ꞉ꜜͼⱷꜛꜛᴢꜜꜝꞌ᷅ͼ᷊᷉᷇᷈Ɫ᷊᷈᷈ӿ⅍Ԑⱡ᷈᷾Ⱡ᷈᷄᷈᷾Ⱡ᷊ͼᴒ᷿᷉᷅

Ⱬᴅ᷄᷉Ⱡ᷊᷇
ⱪꞌ꞉ꜜ꞉ᴐԜꞌͼᴁᴟ꞉Ԝꞌͼ͟ᴟꜝᴡꜝᴐꜝꞌⱡͼⱫᴅ᷄᷉Ⱡ᷊᷊᷇᷄᷇
ⱨꜛᴒꜜᴑꜛᴒꜜᴡͼ᷊᷅᷇ͼⱴ꞉ꜜԜꞌⱡͼ᷇ⱠͼꜗԜꜜᴢԜᴟᴦ᷉᷇᷈ⅎ
ⱪꜝꜜⱱ꞉ᴑᴒꜜᴡ꞉Ԝꞌ
͟ԜⱲᴒͼⱠ᷊
ⱫᴦԜᴥͼⱪꜝᴟꜞ᷅
12 APPENDICES
ⱨꜞꜞᴒꜜᴑ꞉ᴥͼ᷈
͟ᴟꜝᴡꜝᴐꜝꞌͼⱶ꞉ᴠᴡꜝᴟᴦ
ⱨꜞꜞᴒꜜᴑ꞉ᴥͼ᷉
꜠Ԝᴡ꞉ꜝꜜԜꞌͼⱷꜜᴠᴡ꞉ᴡᴢᴡᴒͼꜝⱱͼⱨꞌꞌᴒᴟⱲᴦͼԜꜜᴑͼⱷꜜⱱᴒᴐᴡ꞉ꜝᴢᴠͼⱫ꞉ᴠᴒԜᴠᴒᴠԓͼⱫ꞉ᴣ꞉ᴠ꞉ꜝꜜͼꜝⱱͼꜚ꞉ᴐᴟꜝԝ꞉ꜝꞌꜝⱲᴦͼ
Ԝꜜᴑͼⱷꜜⱱᴒᴐᴡ꞉ꜝᴢᴠͼⱫ꞉ᴠᴒԜᴠᴒᴠͼӿⱫꜚⱷⱫԐͼⱨᴑᴢꞌᴡͼᴁꜝᴥ꞉ᴐ꞉ᴡᴦͼᴁԜԝꞌᴒͼӿꜚꜝᴑ꞉ⱱ꞉ᴒᴑԐͼӿᴂᴀͼ꜠Ԝᴡ꞉ꜝꜜԜꞌͼ
ⱷꜜᴠᴡ꞉ᴡᴢᴡᴒᴠͼꜝⱱͼⱶᴒԜꞌᴡⱳⱢͼ꜠Ԝᴡ꞉ꜝꜜԜꞌͼⱷꜜᴠᴡ꞉ᴡᴢᴡᴒͼꜝⱱͼⱨꞌꞌᴒᴟⱲᴦͼԜꜜᴑͼⱷꜜⱱᴒᴐᴡ꞉ꜝᴢᴠͼⱫ꞉ᴠᴒԜᴠᴒᴠ
ⱨꜞꜞᴒꜜᴑ꞉ᴥͼ᷊
꜠Ԝᴡ꞉ꜝꜜԜꞌͼⱷꜜᴠᴡ꞉ᴡᴢᴡᴒͼꜝⱱͼⱨꞌꞌᴒᴟⱲᴦͼԜꜜᴑͼⱷꜜⱱᴒᴐᴡ꞉ꜝᴢᴠͼⱫ꞉ᴠᴒԜᴠᴒᴠԓͼⱫ꞉ᴣ꞉ᴠ꞉ꜝꜜͼꜝⱱͼꜚ꞉ᴐᴟꜝԝ꞉ꜝꞌꜝⱲᴦͼ
Ԝꜜᴑͼⱷꜜⱱᴒᴐᴡ꞉ꜝᴢᴠͼⱫ꞉ᴠᴒԜᴠᴒᴠͼӿⱫꜚⱷⱫԐͼ͟ᴒᴑ꞉Ԝᴡᴟ꞉ᴐͼᴁꜝᴥ꞉ᴐ꞉ᴡᴦͼᴁԜԝꞌᴒᴠͼӿꜚꜝᴑ꞉ⱱ꞉ᴒᴑԐͼӿᴂᴀͼ
꜠Ԝᴡ꞉ꜝꜜԜꞌͼⱷꜜᴠᴡ꞉ᴡᴢᴡᴒᴠͼꜝⱱͼⱶᴒԜꞌᴡⱳⱢͼ꜠Ԝᴡ꞉ꜝꜜԜꞌͼⱷꜜᴠᴡ꞉ᴡᴢᴡᴒͼꜝⱱͼⱨꞌꞌᴒᴟⱲᴦͼԜꜜᴑͼⱷꜜⱱᴒᴐᴡ꞉ꜝᴢᴠͼⱫ꞉ᴠᴒԜᴠᴒᴠ
ⱨꜞꜞᴒꜜᴑ꞉ᴥͼ᷾
ⱶⱨⱬͼⱨᴡᴡԜᴐꞋͼⱨᴠᴠᴒᴠᴠꜛᴒꜜᴡͼԜꜜᴑͼϸᴒꜞꜝᴟᴡ꞉ꜜⱲͼ͟ᴟꜝᴐᴒᴑᴢᴟᴒᴠͼӿⱶⱨⱨϸ͟Ԑ

Ⱬᴅ᷄᷉Ⱡ᷊᷇
ⱪꞌ꞉ꜜ꞉ᴐԜꞌͼᴁᴟ꞉Ԝꞌͼ͟ᴟꜝᴡꜝᴐꜝꞌⱡͼⱫᴅ᷄᷉Ⱡ᷊᷊᷇᷄᷇
ⱨꜛᴒꜜᴑꜛᴒꜜᴡͼ᷊᷅᷇ͼⱴ꞉ꜜԜꞌⱡͼ᷇ⱠͼꜗԜꜜᴢԜᴟᴦͼ᷉᷇᷈ⅎ
ⱪꜝꜜⱱ꞉ᴑᴒꜜᴡ꞉Ԝꞌ
͟ԜⱲᴒͼⱠ᷾
ⱫᴦԜᴥͼⱪꜝᴟꜞ᷅
Appendix 1
Protocol History
Document
Date
Global/Country/Site Specific
Original Protocol
᷈᷾ͼᴀᴒꜞᴡᴒꜛԝᴒᴟͼ᷿᷉᷇᷈
ⱵꞌꜝԝԜꞌ
Amendment 1.0
᷈᷾ͼⱫᴒᴐᴒꜛԝᴒᴟͼ᷿᷉᷇᷈
ⱵꞌꜝԝԜꞌ
Amendment 2.0
᷉᷈ͼⱨꜞᴟ꞉ꞌͼ᷉᷇᷈⅍
ⱵꞌꜝԝԜꞌ
Amendment 3.0
᷇ⱠͼꜗԜꜜᴢԜᴟᴦ᷉᷇᷈ⅎ
ⱵꞌꜝԝԜꞌ
ᴁⱳᴒͼ͟ᴟꜝᴡꜝᴐꜝꞌͼⱨꜛᴒꜜᴑꜛᴒꜜᴡͼ᷉᷅᷇ͼ꞉ꜜᴐꞌᴢᴑᴒᴠͼᴐⱳԜꜜⱲᴒᴠͼᴡꜝͼᴡⱳᴒͼ͟ᴟꜝᴡꜝᴐꜝꞌͼⱨꜛᴒꜜᴑꜛᴒꜜᴡͼ᷈᷅᷇ԓͼᴠᴢꜛꜛԜᴟ꞉ᴧᴒᴑͼ
Ԝᴠͼⱱꜝꞌꞌꜝᴤᴠⱡ

ⱨꜜͼᴒᴥᴐꞌᴢᴠ꞉ꜝꜜͼᴐᴟ꞉ᴡᴒᴟ꞉ꜝꜜͼᴤԜᴠͼԜᴑᴑᴒᴑͼᴡꜝͼᴒᴥᴐꞌᴢᴑᴒͼᴠᴢԝ꞊ᴒᴐᴡᴠͼᴤⱳꜝͼꜛԜᴦͼⱳԜᴣᴒͼꜞԜᴟᴡ꞉ᴐ꞉ꜞԜᴡᴒᴑͼ꞉ꜜͼԜ
ꜞᴟ꞉ꜝᴟͼⱫᴅ᷄᷉Ⱡ᷊᷇ͼᴠᴡᴢᴑᴦͼᴡꜝͼᴒꞌ꞉ꜛ꞉ꜜԜᴡᴒͼꜜꜝꜜ᷄ꜜԜᵴᴣᴒͼⱱᴟꜝꜛͼᴡⱳᴒͼᴠᴡᴢᴑᴦͼԜꜜԜꞌᴦᴠ꞉ᴠⱢͼᴐꜝꜜᴠᴒꜟᴢᴒꜜᴡꞌᴦԓͼ
ᴠᴡᴟԜᴡ꞉ⱱ꞉ᴐԜᴡ꞉ꜝꜜͼԝᴦͼꜜԜᵴᴣᴒͼᴣᴒᴟᴠᴢᴠͼꜜꜝꜜ᷄ꜜԜᵴᴣᴒͼᴠᴢԝ꞊ᴒᴐᴡᴠͼᴤԜᴠͼᴟᴒꜛꜝᴣᴒᴑͼⱱᴟꜝꜛͼᴡⱳᴒͼᴟԜꜜᴑꜝꜛ꞉ᴧԜᴡ꞉ꜝꜜͼ
ꜞꞌԜꜜͼⱱꜝᴟͼᴡⱳᴒͼᴠᴡᴢᴑᴦ᷅

ᴀ꞉ꜜᴐᴒͼꜜꜝͼᴑԜᴡԜͼꜝꜜͼᴒꜛԝᴟᴦꜝ᷄ⱱᴒᴡԜꞌͼᴑᴒᴣᴒꞌꜝꜞꜛᴒꜜᴡͼᴡꜝᴥ꞉ᴐ꞉ᴡᴦͼԜᴟᴒͼԜᴣԜ꞉ꞌԜԝꞌᴒԓͼꜞᴒᴟͼᴡⱳᴒͼᴐꞌ꞉ꜜ꞉ᴐԜꞌͼᴡᴟ꞉Ԝꞌͼ
ⱱԜᴐ꞉ꞌ꞉ᴡԜᴡ꞉ꜝꜜͼⱲᴟꜝᴢꜞᶳᴠͼӿⱪᴁⱴⱵԐͼᴟᴒᴐꜝꜛꜛᴒꜜᴑԜᴡ꞉ꜝꜜᴠͼᴟᴒꞌԜᴡᴒᴑͼᴡꜝͼᴐꜝꜜᴡᴟԜᴐᴒꜞᴡ꞉ꜝꜜͼԜꜜᴑͼꜞᴟᴒⱲꜜԜꜜᴐᴦͼ
ᴡᴒᴠᴡ꞉ꜜⱲͼ꞉ꜜͼᴐꞌ꞉ꜜ꞉ᴐԜꞌͼᴡᴟ꞉Ԝꞌᴠԓͼᴡⱳᴒͼⱳ꞉Ⱳⱳᴒᴠᴡͼᴟ꞉ᴠꞋͼ꞉ᴠͼԜᴠᴠᴢꜛᴒᴑ᷅ͼᴁⱳᴒᴟᴒⱱꜝᴟᴒԓͼᴡⱳᴒͼ꞉ꜜᴐꞌᴢᴠ꞉ꜝꜜͼᴐᴟ꞉ᴡᴒᴟ꞉ꜝꜜͼ
ⱱꜝᴟͼᴐꜝꜜᴡᴟԜᴐᴒꜞᴡ꞉ꜝꜜͼᴟᴒꜟᴢ꞉ᴟᴒꜛᴒꜜᴡᴠͼᴤԜᴠͼꜛꜝᴑ꞉ⱱ꞉ᴒᴑͼᴡꜝͼᴒꜛꜞⱳԜᴠ꞉ᴧᴒͼᴡⱳᴒᴢᴠᴒͼꜝⱱͼⱳ꞉Ⱳⱳꞌᴦͼᴒⱱⱱᴒᴐᴡ꞉ᴣᴒͼ
ᴐꜝꜜᴡᴟԜᴐᴒꜞᴡ꞉ᴣᴒͼꜛᴒԜᴠᴢᴟᴒᴠͼᴑᴢᴟ꞉ꜜⱲͼᴡᴟᴒԜᴡꜛᴒꜜᴡͼԜꜜᴑͼᴢꜜᴡ꞉ꞌͼᴡⱳᴒͼᴒꜜᴑͼꜝⱱͼᴟᴒꞌᴒᴣԜꜜᴡͼᴠᴦᴠᴡᴒꜛ꞉ᴐͼ
ᴒᴥꜞꜝᴠᴢᴟᴒͼⱱꜝᴟͼᴤꜝꜛᴒꜜͼꜝⱱͼᴐⱳ꞉ꞌᴑԝᴒԜᴟ꞉ꜜⱲͼꜞꜝᴡᴒꜜᴡ꞉Ԝꞌ᷅ͼⱷᴡͼᴤԜᴠͼԜꞌᴠꜝͼᴐꞌԜᴟ꞉ⱱ꞉ᴒᴑͼᴡⱳԜᴡͼᴡⱳᴒͼᴢᴠᴒͼꜝⱱͼԜͼ
ꜛԜꞌᴒͼᴐꜝꜜᴑꜝꜛͼᴤ꞉ᴡⱳͼꜝᴟͼᴤ꞉ᴡⱳꜝᴢᴡͼᴠꜞᴒᴟꜛ꞉ᴐ꞉ᴑᴒͼꜝᴟͼᴐᴒᴟᴣ꞉ᴐԜꞌͼᴐԜꜞԓͼᴑ꞉ԜꜞⱳᴟԜⱲꜛԓ ꜝᴟͼᴠꜞꜝꜜⱲᴒͼᴤ꞉ᴡⱳͼ
ᴠꜞᴒᴟꜛ꞉ᴐ꞉ᴑᴒͼꜝᴟͼԜͼᴐꜝꜛԝ꞉ꜜԜᴡ꞉ꜝꜜͼӿᴑꜝᴢԝꞌᴒ᷄ԝԜᴟᴟ꞉ᴒᴟͼꜛᴒᴡⱳꜝᴑᴠԐͼ꞉ᴠͼꜜꜝᴡͼᴐꜝꜜᴠ꞉ᴑᴒᴟᴒᴑͼⱳ꞉Ⱳⱳꞌᴦͼ
ᴒⱱⱱᴒᴐᴡ꞉ᴣᴒ᷅

ⱴꜝᴢᴟͼԜᴑᴑ꞉ᴡ꞉ꜝꜜԜꞌͼꜞᴟᴒⱲꜜԜꜜᴐᴦͼᴡᴒᴠᴡᴠͼӿᴢᴟ꞉ꜜᴒͼꜝᴟͼᴠᴒᴟᴢꜛԐͼᴤᴒᴟᴒͼᴠᴐⱳᴒᴑᴢꞌᴒᴑͼꜝꜜͼⱫԜᴦᴠͼ᷉˲ԓͼ᷿⅍ԓͼ᷈᷉⅍ԓͼ
Ԝꜜᴑͼ᷿᷈᷾ͼⱱꜝᴟͼꜛꜝꜜ꞉ᴡꜝᴟ꞉ꜜⱲͼꜝⱱͼꜞᴟᴒⱲꜜԜꜜᴐᴦͼᴑᴢᴟ꞉ꜜⱲͼᴡᴟᴒԜᴡꜛᴒꜜᴡ᷅
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͟ᴒᴟͼⱴꜝꜝᴡꜜꜝᴡᴒӺⅎͼ꞉ꜜͼᴡⱳᴒͼᶰᴀᴡᴢᴑᴦͼⱨᴐᴡ꞉ᴣ꞉ᴡ꞉ᴒᴠͼᴀᴐⱳᴒᴑᴢꞌᴒԓᶱͼԜͼᴐꜝᴟᴟᴒᴐᴡ꞉ꜝꜜͼᴤԜᴠͼꜛԜᴑᴒͼ꞉ꜜͼᴀᴒᴐᴡ꞉ꜝꜜͼ
ⅎͼӿᴀᴡᴢᴑᴦͼⱨᴐᴡ꞉ᴣ꞉ᴡ꞉ᴒᴠԐͼᴡⱳԜᴡͼԜͼᴠᴒᴟᴢꜛ᷄ꜝᴟͼᴢᴟ꞉ꜜᴒ᷄ԝԜᴠᴒᴑͼꜞᴟᴒⱲꜜԜꜜᴐᴦͼᴡᴒᴠᴡͼᴤ꞉ꞌꞌͼԝᴒͼꜞᴒᴟⱱꜝᴟꜛᴒᴑͼԜᴡͼ
ᴡⱳᴒͼⱴ꞉ꜜԜꞌͼⱴꜝꞌꞌꜝᴤ᷄ᴢꜞͼᴃ꞉ᴠ꞉ᴡͼӿᴀᴢԝ꞊ᴒᴐᴡᴠͼ꜠ꜝᴡͼⱪꜝꜜᴡ꞉ꜜᴢ꞉ꜜⱲͼ꞉ꜜͼ꜡ꜞᴒꜜ᷄ꜙԜԝᴒꞌͼⱬᴥᴡᴒꜜᴠ꞉ꜝꜜͼᴀᴡᴢᴑᴦԐⱡͼ
ᴃ꞉ᴠ꞉ᴡͼ᷈⅍ԓͼⱫԜᴦͼ᷊᷉˲ͼᶐͼⱫԜᴦᴠ᷅
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ⱷᴡͼᴤԜᴠͼᴐꞌԜᴟ꞉ⱱ꞉ᴒᴑͼᴡⱳԜᴡͼꜜꜝͼ꞉ꜜᴡᴒᴟ꞉ꜛͼԜꜜԜꞌᴦᴠ꞉ᴠͼ꞉ᴠͼꜞꞌԜꜜꜜᴒᴑ᷅
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ⱨꜜͼ꞉ꜜᴑᴒꜞᴒꜜᴑᴒꜜᴡͼⱫԜᴡԜͼᴀԜⱱᴒᴡᴦͼꜚꜝꜜ꞉ᴡꜝᴟ꞉ꜜⱲͼⱩꜝԜᴟᴑͼӿⱫᴀꜚⱩԐͼᴟᴒꜞꞌԜᴐᴒᴑͼᴡⱳᴒͼ꞉ꜜᴡᴒᴟꜜԜꞌͼᴠᴡᴢᴑᴦͼ
ᴠԜⱱᴒᴡᴦͼᴐꜝꜛꜛ꞉ᴡᴡᴒᴒͼӿᴀᴀⱪԐԓͼԜꜜᴑͼ꞉ᴡᴠͼꜞᴟꜝᴐᴒᴑᴢᴟᴒᴠͼᴤᴒᴟᴒͼᴐꞌԜᴟ꞉ⱱ꞉ᴒᴑ᷅
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ᴁⱳᴒͼꜞᴒᴟ꞉ꜝᴑͼⱱꜝᴟͼᴟᴒꜞꜝᴟᴡ꞉ꜜⱲͼⱶⱨⱬͼԜᴡᴡԜᴐꞋᴠͼԜⱱᴡᴒᴟͼᴡⱳᴒͼⱱ꞉ꜜԜꞌⱱꜝꞌꞌꜝᴤ᷄ᴢꜞͼᴣ꞉ᴠ꞉ᴡͼᴤԜᴠͼᴐꞌԜᴟ꞉ⱱ꞉ᴒᴑ᷅
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ⱴꜝᴟͼᴡⱳᴒͼꜛԜꜜԜⱲᴒꜛᴒꜜᴡͼꜝⱱͼԜᴐᴢᴡᴒͼⱶⱨⱬͼԜᴡᴡԜᴐꞋᴠԓͼ꞉ᴡͼᴤԜᴠͼᴐꞌԜᴟ꞉ⱱ꞉ᴒᴑͼᴡⱳԜᴡͼԜᴑꜛ꞉ꜜ꞉ᴠᴡᴟԜᴡ꞉ꜝꜜͼꜝⱱͼᴡⱳᴒͼ
꞉ꜜᴣᴒᴠᴡ꞉ⱲԜᴡ꞉ꜝꜜԜꞌͼꜞᴟꜝᴑᴢᴐᴡͼԜꜜᴑͼᴠᴡᴢᴑᴦͼꜞᴟꜝᴐᴒᴑᴢᴟᴒᴠͼᴤ꞉ꞌꞌͼᴐꜝꜜᴡ꞉ꜜᴢᴒͼᴤ꞉ᴡⱳꜝᴢᴡͼԜꞌᴡᴒᴟԜᴡ꞉ꜝꜜͼᴡꜝͼᴡⱳᴒͼ
ꜞᴟꜝᴡꜝᴐꜝꞌ᷄ᴠꜞᴒᴐ꞉ⱱ꞉ᴒᴑͼᴠᴡᴢᴑᴦͼᴠᴐⱳᴒᴑᴢꞌᴒԓͼᴒᴣᴒꜜͼ꞉ⱱͼᴡⱳᴒͼꜞԜᴡ꞉ᴒꜜᴡᴟᴒᴐᴒ꞉ᴣᴒᴠͼԜꜜᴦͼᴡᴟᴒԜᴡꜛᴒꜜᴡͼⱱꜝᴟͼԜꜜͼ
ⱶⱨⱬͼԜᴡᴡԜᴐꞋ᷅
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ⱴꜝᴟͼᴐꜝꞌꞌᴒᴐᴡ꞉ꜝꜜͼꜝⱱͼⱶⱨⱬͼԜᴡᴡԜᴐꞋͼᴑԜᴡԜԓͼ꞉ᴡͼᴤԜᴠͼᴐꞌԜᴟ꞉ⱱ꞉ᴒᴑͼᴡⱳԜᴡͼᴤᴒᴒꞋꞌᴦͼᴐꜝꜛꜛᴢꜜ꞉ᴐԜᴡ꞉ꜝꜜͼ
ԝᴒᴡᴤᴒᴒꜜͼᴡⱳᴒͼꜞԜᴡ꞉ᴒꜜᴡᴠͼԜꜜᴑͼᴡⱳᴒͼᴠ꞉ᴡᴒԓͼ꞉ꜜᴐꞌᴢᴑ꞉ꜜⱲͼᴟᴒꜞꜝᴟᴡᴠͼꜝⱱͼⱶⱨⱬͼԜᴡᴡԜᴐꞋᴠԓͼꜛᴢᴠᴡͼԝᴒͼ
ᴑꜝᴐᴢꜛᴒꜜᴡᴒᴑͼ꞉ꜜͼᴡⱳᴒͼᴒⱪϸⱴ᷅
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ⱨͼᴡᴒᴟᴡ꞉Ԝᴟᴦͼꜝԝ꞊ᴒᴐᴡ꞉ᴣᴒͼᴡꜝͼᴒᴣԜꞌᴢԜᴡᴒͼᴡⱳᴒͼᴒⱱⱱᴒᴐᴡͼꜝⱱͼⱫᴅ᷄᷉Ⱡ᷊᷇ͼꜝꜜͼⱳᴒԜꞌᴡⱳ᷄ᴟᴒꞌԜᴡᴒᴑͼꜟᴢԜꞌ꞉ᴡᴦͼꜝⱱͼꞌ꞉ⱱᴒͼ
ӿϷꜝꜙԐͼᴤԜᴠͼᴟᴒꜞⱳᴟԜᴠᴒᴑͼⱱꜝᴟͼᴐꞌԜᴟ꞉ᴡᴦ᷅
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ⱴꜝᴢᴟͼԜᴑᴑ꞉ᴡ꞉ꜝꜜԜꞌͼϷꜝꜙͼԜᴠᴠᴒᴠᴠꜛᴒꜜᴡᴠͼᴢᴠ꞉ꜜⱲͼᴡⱳᴒͼⱨꜜⱲ꞉ꜝᴒᴑᴒꜛԜ᷄ϷᴢԜꞌ꞉ᴡᴦͼꜝⱱͼꜙ꞉ⱱᴒͼӿⱨⱬ᷄ϷꜝꜙԐͼ
Ϸᴢᴒᴠᴡ꞉ꜝꜜꜜԜ꞉ᴟᴒͼᴤᴒᴟᴒͼԜᴑᴑᴒᴑͼԜᴡͼⱫԜᴦͼ᷉˲ͼᶐ᷊ԓͼⱫԜᴦͼ᷿⅍ͼᶐ᷊ԓͼⱫԜᴦͼ᷈᷉⅍ͼᶐ᷊ԓͼⱫԜᴦͼ᷿᷈᷾ͼᶐ᷊ͼ꞉ꜜͼᴡᴒᴥᴡͼ

Ⱬᴅ᷄᷉Ⱡ᷊᷇
ⱪꞌ꞉ꜜ꞉ᴐԜꞌͼᴁᴟ꞉Ԝꞌͼ͟ᴟꜝᴡꜝᴐꜝꞌⱡͼⱫᴅ᷄᷉Ⱡ᷊᷊᷇᷄᷇
ⱨꜛᴒꜜᴑꜛᴒꜜᴡͼ᷊᷅᷇ͼⱴ꞉ꜜԜꞌⱡͼ᷇ⱠͼꜗԜꜜᴢԜᴟᴦͼ᷉᷇᷈ⅎ
ⱪꜝꜜⱱ꞉ᴑᴒꜜᴡ꞉Ԝꞌ
͟ԜⱲᴒͼⱠ᷿
ⱫᴦԜᴥͼⱪꜝᴟꜞ᷅
Ԝꜜᴑͼ꞉ꜜͼᴡⱳᴒͼᴀᴡᴢᴑᴦͼⱨᴐᴡ꞉ᴣ꞉ᴡ꞉ᴒᴠͼᴀᴐⱳᴒᴑᴢꞌᴒͼⱱꜝᴟͼԜͼԝᴒᴡᴡᴒᴟͼꜛᴒԜᴠᴢᴟᴒͼԜꜜᴑͼᴐꜝꜛꜞԜᴟ꞉ᴠꜝꜜͼꜝⱱͼᴡⱳᴒͼᴑԜᴡԜͼ
ԜᴣԜ꞉ꞌԜԝꞌᴒͼⱱᴟꜝꜛͼᴡⱳᴒͼᴠᴡᴢᴑᴦ᷅
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ⱷᴡͼᴤԜᴠͼᴠꜞᴒᴐ꞉ⱱ꞉ᴒᴑͼ꞉ꜜͼᴀᴒᴐᴡ꞉ꜝꜜͼⅎ᷅᷈ͼӿᴀᴡᴢᴑᴦͼⱨᴐᴡ꞉ᴣ꞉ᴡ꞉ᴒᴠ᷄ᴀᴐᴟᴒᴒꜜ꞉ꜜⱲԐͼᴡⱳԜᴡͼᴡⱳᴒͼᴤԜᴠⱳꜝᴢᴡͼԜⱱᴡᴒᴟͼᴡⱳᴒͼ
ꞌꜝꜜⱲ᷄ᴡᴒᴟꜛͼꜞᴟꜝꜞⱳᴦꞌԜᴐᴡ꞉ᴐͼӿꜙᴁ͟ԐͼᴡⱳᴒᴟԜꜞᴦͼ꞉ᴠͼꜞᴒᴟꜛ꞉ᴡᴡᴒᴑͼԜᴠͼꞌꜝꜜⱲͼԜᴠͼᴡⱳᴒͼⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟͼ
ᴑᴒᴡᴒᴟꜛ꞉ꜜᴒᴑͼᴡⱳԜᴡͼᴑꜝ꞉ꜜⱲͼᴠꜝͼᴤꜝᴢꞌᴑͼꜜꜝᴡͼꜞꞌԜᴐᴒͼᴡⱳᴒͼᴠᴢԝ꞊ᴒᴐᴡͼԜᴡͼԜꜜᴦͼᴢꜜᴑᴢᴒͼᴠԜⱱᴒᴡᴦͼᴟ꞉ᴠꞋͼԜꜜᴑͼ
ᴤꜝᴢꞌᴑͼԝᴒͼԜꜞꜞꞌ꞉ᴐԜԝꞌᴒͼᴡꜝͼᴠᴢԝ꞊ᴒᴐᴡᴠͼᴤⱳꜝͼԜᴟᴒͼԜᴡͼꞌᴒԜᴠᴡͼ᷈˲ͼᴦᴒԜᴟᴠͼꜝⱱͼԜⱲᴒ᷅
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ⱨͼᴠԜⱱᴒᴡᴦͼԜᴠᴠᴒᴠᴠꜛᴒꜜᴡԓͼ᷈᷉᷄ꞌᴒԜᴑͼᴒꞌᴒᴐᴡᴟꜝᴐԜᴟᴑ꞉ꜝⱲᴟԜꜛͼӿⱬⱪⱵԐԓͼᴤԜᴠͼԜᴑᴑᴒᴑͼԜᴡͼᴃ꞉ᴠ꞉ᴡͼ᷈⅍᷆ⱫԜᴦͼ
᷊᷉˲ͼ꞉ꜜͼᴡⱳᴒͼᴡԜԝꞌᴒᴠͼⱱꜝᴟͼᶰᴠᴡᴢᴑᴦͼԜᴐᴡ꞉ᴣ꞉ᴡ꞉ᴒᴠͼᴠᴐⱳᴒᴑᴢꞌᴒᴠᶱͼᴡꜝͼԝᴒͼᴐꜝꜜᴠ꞉ᴠᴡᴒꜜᴡͼᴤ꞉ᴡⱳͼᴀᴒᴐᴡ꞉ꜝꜜͼⅎ᷅᷈ⅎԓͼ
ⱴ꞉ꜜԜꞌͼⱴꜝꞌꞌꜝᴤ᷄ᴢꜞͼᴃ꞉ᴠ꞉ᴡͼӿᴠᴢԝ꞊ᴒᴐᴡᴠͼꜜꜝᴡͼᴐꜝꜜᴡ꞉ꜜᴢ꞉ꜜⱲͼ꞉ꜜͼ꜡ꜞᴒꜜ᷄ꜙԜԝᴒꞌͼⱬᴥᴡᴒꜜᴠ꞉ꜝꜜͼᴀᴡᴢᴑᴦԐ᷅
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ᴁⱳᴒͼᴒⱱⱱ꞉ᴐԜᴐᴦͼᴒᴣԜꞌᴢԜᴡ꞉ꜝꜜͼꜞᴒᴟ꞉ꜝᴑͼᴤԜᴠͼᴢꜞᴑԜᴡᴒᴑͼᴡꜝͼԝᴒⱲ꞉ꜜͼԜᴡͼⱫԜᴦͼ᷇ͼ꞉ꜜᴠᴡᴒԜᴑͼꜝⱱͼⱫԜᴦͼ᷈᷾ͼᴡꜝͼԝᴒͼ
ᴐꜝꜜᴠ꞉ᴠᴡᴒꜜᴡͼᴤ꞉ᴡⱳͼᴡⱳᴒͼ꞉ꜜᴡᴒꜜᴡ᷄ᴡꜝ᷄ᴡᴟᴒԜᴡͼԜꜜԜꞌᴦᴠ꞉ᴠͼꜞᴟ꞉ꜜᴐ꞉ꜞꞌᴒ᷅
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ᴁⱳᴒͼᴑᴒᴠᴐᴟ꞉ꜞᴡ꞉ꜝꜜͼꜝⱱͼᴡⱳᴒͼꜞᴟ꞉ꜛԜᴟᴦͼᴒꜜᴑꜞꜝ꞉ꜜᴡͼᴤԜᴠͼꜛꜝᴑ꞉ⱱ꞉ᴒᴑͼⱱꜝᴟͼԜᴠᴠᴒᴠᴠꜛᴒꜜᴡͼᴑᴢᴟ꞉ꜜⱲͼᴡⱳᴒͼ
ᴒⱱⱱ꞉ᴐԜᴐᴦͼᴒᴣԜꞌᴢԜᴡ꞉ꜝꜜͼꜞᴒᴟ꞉ꜝᴑͼᴟԜᴡⱳᴒᴟͼᴡⱳԜꜜͼꜞᴒᴟͼᴤᴒᴒꞋͼⱱꜝᴟͼᴐꜝꜜᴠ꞉ᴠᴡᴒꜜᴐᴦͼᴤ꞉ᴡⱳͼᴡⱳᴒͼᴠᴡԜᴡ꞉ᴠᴡ꞉ᴐԜꞌͼ
ꜛꜝᴑᴒꞌ᷅ͼᴁⱳᴒͼᴢꜜ꞉ᴡͼꜝⱱͼꜛᴒԜᴠᴢᴟᴒꜛᴒꜜᴡͼ꞉ᴠͼ꞉ᴟᴟᴒꞌᴒᴣԜꜜᴡͼⱱꜝᴟͼᴡⱳᴒͼᴠᴡԜᴡ꞉ᴠᴡ꞉ᴐԜꞌͼꜛꜝᴑᴒꞌͼԜᴠͼᴡⱳᴒͼ
ⱳᴦꜞꜝᴡⱳᴒᴠ꞉ᴠͼᴡᴒᴠᴡͼ꞉ᴠͼԝԜᴠᴒᴑͼꜝꜜͼᴡⱳᴒͼᴟԜᴡᴒͼᴟԜᴡ꞉ꜝ᷅ͼϸᴒᴠᴢꞌᴡᴠͼⱱᴟꜝꜛͼᴡⱳᴒͼᴠᴡԜᴡ꞉ᴠᴡ꞉ᴐԜꞌͼꜛꜝᴑᴒꞌͼᴤ꞉ꞌꞌͼԝᴒͼ
ᴟᴒꜞꜝᴟᴡᴒᴑͼ꞉ꜜͼԝꜝᴡⱳͼᴤᴒᴒꞋᴠͼԜꜜᴑͼꜛꜝꜜᴡⱳᴠͼᴡꜝͼⱱԜᴐ꞉ꞌ꞉ᴡԜᴡᴒͼᴐꞌ꞉ꜜ꞉ᴐԜꞌͼ꞉ꜜᴡᴒᴟꜞᴟᴒᴡԜᴡ꞉ꜝꜜ᷅
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ᴁⱳᴒͼᴠᴒᴐꜝꜜᴑԜᴟᴦͼᴒꜜᴑꜞꜝ꞉ꜜᴡͼᶰᴁ꞉ꜛᴒͼᴡꜝͼⱱ꞉ᴟᴠᴡͼԜᴡᴡԜᴐꞋԓͼ꞉᷅ᴒ᷅ԓͼᴑᴢᴟԜᴡ꞉ꜝꜜͼᴡⱳԜᴡͼԜͼᴠᴢԝ꞊ᴒᴐᴡͼ꞉ᴠͼԜᴡᴡԜᴐꞋͼⱱᴟᴒᴒͼ
ᴢꜜᴡ꞉ꞌͼᴡⱳᴒ꞉ᴟͼⱱ꞉ᴟᴠᴡͼԜᴡᴡԜᴐꞋᶱͼᴤԜᴠͼᴟᴒꜛꜝᴣᴒᴑͼⱱᴟꜝꜛͼᴡⱳᴒͼᴟԜꜜꞋͼꜝᴟᴑᴒᴟͼԜꜜᴑͼᴤ꞉ꞌꞌͼԝᴒͼᴐꜝꜜᴠ꞉ᴑᴒᴟᴒᴑͼԜꜜͼ
ᴒᴥꜞꞌꜝᴟԜᴡꜝᴟᴦͼᴒꜜᴑꜞꜝ꞉ꜜᴡ᷅ͼⱷᴡͼᴤԜᴠͼꜛꜝᴑ꞉ⱱ꞉ᴒᴑͼᴡꜝͼᶰᴁ꞉ꜛᴒͼᴡꜝͼⱱ꞉ᴟᴠᴡͼⱶⱨⱬͼԜᴡᴡԜᴐꞋͼԜⱱᴡᴒᴟͼⱫԜᴦͼ᷈᷾ԓͼ꞉ᴒԓͼ
ᴑᴢᴟԜᴡ꞉ꜝꜜͼᴡⱳԜᴡͼԜͼᴠᴢԝ꞊ᴒᴐᴡͼ꞉ᴠͼԜᴡᴡԜᴐꞋͼⱱᴟᴒᴒͼԜⱱᴡᴒᴟͼⱫԜᴦͼ᷈᷾ᶱͼᴡꜝͼԜꞌꞌꜝᴤͼᴒꜜꜝᴢⱲⱳͼᴡ꞉ꜛᴒͼᴡꜝͼⱱ꞉ᴟᴠᴡͼԜᴡᴡԜᴐꞋͼ
ⱱꜝᴟͼᴡⱳ꞉ᴠͼᴒꜜᴑꜞꜝ꞉ꜜᴡͼԜᴠᴠᴒᴠᴠꜛᴒꜜᴡ᷅

ᴁⱳᴒͼᴠᴒᴐꜝꜜᴑԜᴟᴦͼᴒꜜᴑꜞꜝ꞉ꜜᴡͼᶰ꜠ᴢꜛԝᴒᴟͼꜝⱱͼⱳ꞉Ⱳⱳ᷄ꜛꜝᴟԝ꞉ᴑ꞉ᴡᴦͼⱶⱨⱬͼԜᴡᴡԜᴐꞋᴠᶱͼᴟᴒꜛꜝᴣᴒᴑͼⱱᴟꜝꜛͼᴡⱳᴒͼ
ᴟԜꜜꞋͼꜝᴟᴑᴒᴟͼԜꜜᴑͼᴤ꞉ꞌꞌͼԝᴒͼᴐꜝꜜᴠ꞉ᴑᴒᴟᴒᴑͼԜꜜͼᴒᴥꜞꞌꜝᴟԜᴡꜝᴟᴦͼᴒꜜᴑꜞꜝ꞉ꜜᴡ᷅

ᴁⱳᴒͼᴑᴒᴠᴐᴟ꞉ꜞᴡ꞉ꜝꜜͼꜝⱱͼᴡⱳᴒͼᴠᴒᴐꜝꜜᴑԜᴟᴦͼᴒꜜᴑꜞꜝ꞉ꜜᴡᴠͼᴤԜᴠͼꜛꜝᴑ꞉ⱱ꞉ᴒᴑͼⱱꜝᴟͼԜᴠᴠᴒᴠᴠꜛᴒꜜᴡͼᴑᴢᴟ꞉ꜜⱲͼᴡⱳᴒͼ
ᴒⱱⱱ꞉ᴐԜᴐᴦͼᴒᴣԜꞌᴢԜᴡ꞉ꜝꜜͼꜞᴒᴟ꞉ꜝᴑͼᴟԜᴡⱳᴒᴟͼᴡⱳԜꜜͼꜞᴒᴟͼᴤᴒᴒꞋͼᴡꜝͼⱱꜝᴟͼᴐꜝꜜᴠ꞉ᴠᴡᴒꜜᴐᴦͼᴤ꞉ᴡⱳͼᴡⱳᴒͼᴠᴡԜᴡ꞉ᴠᴡ꞉ᴐԜꞌͼ
ꜛꜝᴑᴒꞌ᷅ͼᴁⱳᴒͼᴢꜜ꞉ᴡͼꜝⱱͼꜛᴒԜᴠᴢᴟᴒꜛᴒꜜᴡͼ꞉ᴠͼ꞉ᴟᴟᴒꞌᴒᴣԜꜜᴡͼⱱꜝᴟͼᴡⱳᴒͼᴠᴡԜᴡ꞉ᴠᴡ꞉ᴐԜꞌͼꜛꜝᴑᴒꞌͼԜᴠͼᴡⱳᴒͼ
ⱳᴦꜞꜝᴡⱳᴒᴠ꞉ᴠͼᴡᴒᴠᴡͼ꞉ᴠͼԝԜᴠᴒᴑͼꜝꜜͼᴡⱳᴒͼᴟԜᴡᴒͼᴟԜᴡ꞉ꜝ᷅ͼϸᴒᴠᴢꞌᴡᴠͼⱱᴟꜝꜛͼᴡⱳᴒͼᴠᴡԜᴡ꞉ᴠᴡ꞉ᴐԜꞌͼꜛꜝᴑᴒꞌͼᴤ꞉ꞌꞌͼԝᴒͼ
ᴟᴒꜞꜝᴟᴡᴒᴑͼ꞉ꜜͼԝꜝᴡⱳͼᴤᴒᴒꞋᴠͼԜꜜᴑͼꜛꜝꜜᴡⱳᴠͼᴡꜝͼⱱԜᴐ꞉ꞌ꞉ᴡԜᴡᴒͼᴐꞌ꞉ꜜ꞉ᴐԜꞌͼ꞉ꜜᴡᴒᴟꜞᴟᴒᴡԜᴡ꞉ꜝꜜ᷅

ᴀᴡԜᴡ꞉ᴠᴡ꞉ᴐԜꞌͼꜛᴒᴡⱳꜝᴑᴠͼᴤᴒᴟᴒͼᴢꜞᴑԜᴡᴒᴑͼᴡꜝͼᴢᴠᴒͼԜͼⱲᴒꜜᴒᴟԜꞌ꞉ᴧᴒᴑͼꞌ꞉ꜜᴒԜᴟͼꜛꜝᴑᴒꞌͼᴟԜᴡⱳᴒᴟͼᴡⱳԜꜜͼ
ⱲᴒꜜᴒᴟԜꞌ꞉ᴧᴒᴑͼᴒᴠᴡ꞉ꜛԜᴡ꞉ꜜⱲͼᴒꜟᴢԜᴡ꞉ꜝꜜͼꜛꜝᴑᴒꞌͼⱱꜝᴟͼᴡⱳᴒͼꜞᴟ꞉ꜛԜᴟᴦͼԜꜜԜꞌᴦᴠ꞉ᴠ᷅ͼᴁⱳ꞉ᴠͼᴢꜞᴑԜᴡᴒᴑͼԜꜜԜꞌᴦᴠ꞉ᴠͼ
ԜꜞꜞᴟꜝԜᴐⱳͼԜꞌᴠꜝͼԜꜞꜞꞌ꞉ᴒᴠͼᴡꜝͼᴡⱳᴒͼᴠᴒᴐꜝꜜᴑԜᴟᴦͼᴒꜜᴑꜞꜝ꞉ꜜᴡᴠ᷅

ꜚᴢꞌᴡ꞉ꜞꞌ꞉ᴐ꞉ᴡᴦͼꜞᴟꜝᴐᴒᴑᴢᴟᴒᴠͼᴤᴒᴟᴒͼᴠꜞᴒᴐ꞉ⱱ꞉ᴒᴑͼ꞉ꜜͼⱲᴟᴒԜᴡᴒᴟͼᴑᴒᴡԜ꞉ꞌ᷅ͼᴀꜞᴒᴐ꞉ⱱ꞉ᴐԜꞌꞌᴦԓͼԜͼⱲᴒꜜᴒᴟԜꞌͼ
ⱲԜᴡᴒꞋᴒᴒꜞ꞉ꜜⱲͼꜞᴟꜝᴐᴒᴑᴢᴟᴒͼᴤ꞉ꞌꞌͼԝᴒͼᴢᴠᴒᴑͼᴡꜝͼᴠᴡᴟꜝꜜⱲꞌᴦͼᴐꜝꜜᴡᴟꜝꞌͼᴡⱳᴒͼⱲꞌꜝԝԜꞌͼⱱԜꜛ꞉ꞌᴦ᷄ᴤ꞉ᴠᴒͼᴁᴦꜞᴒͼⱷͼ
ᴒᴟᴟꜝᴟͼᴟԜᴡᴒͼӿⱴᴄⱬϸԐͼ꞉ꜜͼᴡⱳᴒͼⱳ꞉ᴒᴟԜᴟᴐⱳ꞉ᴐԜꞌͼᴡᴒᴠᴡ꞉ꜜⱲͼꜝⱱͼᴡⱳᴒͼꜞᴟ꞉ꜛԜᴟᴦͼԜꜜᴑͼᴠᴒᴐꜝꜜᴑԜᴟᴦͼᴒꜜᴑꜞꜝ꞉ꜜᴡᴠͼ
ᴐꜝꜜᴑᴢᴐᴡᴒᴑͼԜᴡͼᴡⱳᴒͼ᷈᷅⅍ⅎӼͼᴠ꞉Ⱳꜜ꞉ⱱ꞉ᴐԜꜜᴐᴒͼꞌᴒᴣᴒꞌͼⱱꜝᴟͼᴒԜᴐⱳͼԜᴐᴡ꞉ᴣᴒͼᴡᴟᴒԜᴡꜛᴒꜜᴡͼⱲᴟꜝᴢꜞͼᴐꜝꜛꜞԜᴟᴒᴑͼ
ᴤ꞉ᴡⱳͼᴡⱳᴒͼꜞꞌԜᴐᴒԝꜝͼⱲᴟꜝᴢꜞ᷅

ⱷꜜͼⱲᴒꜜᴒᴟԜꞌԓͼᴡⱳᴒͼᴠᴡԜᴡ꞉ᴠᴡ꞉ᴐԜꞌͼꜛᴒᴡⱳꜝᴑᴠͼᴤᴒᴟᴒͼᴑᴒᴠᴐᴟ꞉ԝᴒᴑͼᴤ꞉ᴡⱳͼԜᴑᴑ꞉ᴡ꞉ꜝꜜԜꞌͼ꞉ꜜⱱꜝᴟꜛԜᴡ꞉ꜝꜜͼ
ᴟᴒⱲԜᴟᴑ꞉ꜜⱲͼᴡⱳᴒͼⱲᴒꜜᴒᴟԜꞌͼᴠᴡԜᴡ꞉ᴠᴡ꞉ᴐԜꞌͼᴐꜝꜜᴠ꞉ᴑᴒᴟԜᴡ꞉ꜝꜜᴠͼԜꜜᴑͼᴠᴡԜᴡ꞉ᴠᴡ꞉ᴐԜꞌ᷆ԜꜜԜꞌᴦᴡ꞉ᴐԜꞌͼ꞉ᴠᴠᴢᴒᴠͼӿᴒⱲԓͼ
Ԝᴑ꞊ᴢᴠᴡꜛᴒꜜᴡͼⱱꜝᴟͼᴐꜝᴣԜᴟ꞉ԜᴡᴒᴠԓͼⱳԜꜜᴑꞌ꞉ꜜⱲͼꜝⱱͼᴑᴟꜝꜞꜝᴢᴡᴠͼԜꜜᴑͼᴑԜᴡԜͼꜛꜝꜜ꞉ᴡꜝᴟ꞉ꜜⱲԓͼⱳԜꜜᴑꞌ꞉ꜜⱲͼꜝⱱͼ
ᴑᴟꜝꜞꜝᴢᴡᴠͼꜝᴟͼꜛ꞉ᴠᴠ꞉ꜜⱲͼᴑԜᴡԜԓͼ꞉ꜜᴡᴒᴟ꞉ꜛͼԜꜜԜꞌᴦᴠ꞉ᴠͼԜꜜᴑͼᴑԜᴡԜͼꜛꜝꜜ꞉ᴡꜝᴟ꞉ꜜⱲԓͼꜛᴢꞌᴡ꞉ᴐᴒꜜᴡᴒᴟͼᴠᴡᴢᴑ꞉ᴒᴠԓͼ
Ԝꜜᴑͼᴠᴒꜜᴠ꞉ᴡ꞉ᴣ꞉ᴡᴦͼԜꜜԜꞌᴦᴠᴒᴠԐ᷅

ᴀԜꜛꜞꞌᴒᴠ꞉ᴧᴒͼᴑᴒᴡᴒᴟꜛ꞉ꜜԜᴡ꞉ꜝꜜͼᴤԜᴠͼᴢꜞᴑԜᴡᴒᴑͼᴡꜝͼԝᴒͼᴐꜝꜜᴠ꞉ᴠᴡᴒꜜᴡͼᴤ꞉ᴡⱳͼᴡⱳᴒͼᴢꜞᴑԜᴡᴒᴑͼᴠᴡԜᴡ꞉ᴠᴡ꞉ᴐԜꞌͼ
ꜛᴒᴡⱳꜝᴑᴠ᷅ͼ

ᴀᴒᴐᴡ꞉ꜝꜜͼ᷈᷇᷅Ⱡԓͼ͟ᴟᴒꜛԜᴡᴢᴟᴒͼⱪꞌꜝᴠᴢᴟᴒͼꜝⱱͼᴡⱳᴒͼᴀᴡᴢᴑᴦԓͼᴤԜᴠͼԜᴑᴑᴒᴑͼᴡꜝͼ꞉ꜜᴐꞌᴢᴑᴒͼᴐꜝꜜᴑ꞉ᴡ꞉ꜝꜜᴠͼᴡⱳԜᴡͼ
ꜛԜᴦͼᴤԜᴟᴟԜꜜᴡͼᴡᴒᴟꜛ꞉ꜜԜᴡ꞉ꜝꜜͼꜝⱱͼᴡⱳᴒͼᴠᴡᴢᴑᴦͼꜝᴟͼᴠ꞉ᴡᴒ᷅

Ⱬᴅ᷄᷉Ⱡ᷊᷇
ⱪꞌ꞉ꜜ꞉ᴐԜꞌͼᴁᴟ꞉Ԝꞌͼ͟ᴟꜝᴡꜝᴐꜝꞌⱡͼⱫᴅ᷄᷉Ⱡ᷊᷊᷇᷄᷇
ⱨꜛᴒꜜᴑꜛᴒꜜᴡͼ᷊᷅᷇ͼⱴ꞉ꜜԜꞌⱡͼ᷇ⱠͼꜗԜꜜᴢԜᴟᴦͼ᷉᷇᷈ⅎ
ⱪꜝꜜⱱ꞉ᴑᴒꜜᴡ꞉Ԝꞌ
͟ԜⱲᴒͼⱠ⅍
ⱫᴦԜᴥͼⱪꜝᴟꜞ᷅

ᴀᴒᴐᴡ꞉ꜝꜜͼ᷈᷇᷅᷈᷉ԓͼⱫԜᴡԜͼⱶԜꜜᴑꞌ꞉ꜜⱲͼⱪꜝꜜᴠ꞉ᴑᴒᴟԜᴡ꞉ꜝꜜᴠԓͼᴤԜᴠͼԜᴑᴑᴒᴑͼᴡꜝͼ꞉ꜜᴐꞌᴢᴑᴒͼᴠꜞᴒᴐ꞉ⱱ꞉ᴐᴠͼ
ᴟᴒⱲԜᴟᴑ꞉ꜜⱲͼⱳԜꜜᴑꞌ꞉ꜜⱲͼꜝⱱͼᴑԜᴡԜͼᴡꜝͼꜞᴟᴒᴣᴒꜜᴡͼꜞꜝᴡᴒꜜᴡ꞉Ԝꞌͼᴢꜜԝꞌ꞉ꜜᴑ꞉ꜜⱲ᷅

ⱷꜜͼᴀᴒᴐᴡ꞉ꜝꜜͼ᷈᷇᷅᷈᷾ԓͼⱱ꞉ꜜԜꜜᴐ꞉Ԝꞌͼᴑ꞉ᴠᴐꞌꜝᴠᴢᴟᴒͼꞌԜꜜⱲᴢԜⱲᴒͼᴤԜᴠͼᴢꜞᴑԜᴡᴒᴑͼᴡꜝͼԝᴒͼᴐꜝꜜᴠ꞉ᴠᴡᴒꜜᴡͼᴤ꞉ᴡⱳͼ᷉᷈ͼ
ⱪⱴϸͼ᷿᷾ͼ᷉ӿԝԐͼӿ᷈ⱠⱠ˲Ԑ᷅

ᴀᴒᴐᴡ꞉ꜝꜜͼ᷿᷈᷇᷅᷈ԓͼᴀᴡᴢᴑᴦͼϸᴒᴠᴢꞌᴡᴠ᷆͟ᴢԝꞌ꞉ᴐԜᴡ꞉ꜝꜜͼ͟ꜝꞌ꞉ᴐᴦԓͼᴤԜᴠͼᴢꜞᴑԜᴡᴒᴑͼᴡꜝͼ꞉ꜜᴐꞌᴢᴑᴒͼꞌԜꜜⱲᴢԜⱲᴒͼ
ᴟᴒⱲԜᴟᴑ꞉ꜜⱲͼꜞꜝᴠᴡ꞉ꜜⱲͼꜝⱱͼԜꜞꜞᴟꜝꜞᴟ꞉Ԝᴡᴒͼᴠᴡᴢᴑᴦͼ꞉ꜜⱱꜝᴟꜛԜᴡ꞉ꜝꜜͼꜝꜜͼԜꜞꜞꞌ꞉ᴐԜԝꞌᴒͼᴤᴒԝᴠ꞉ᴡᴒᴠͼԝᴦͼᴡⱳᴒͼ
ᴀꜞꜝꜜᴠꜝᴟ᷅

ᴀꜞꜝꜜᴠꜝᴟԓͼᴀꜞꜝꜜᴠꜝᴟͼᴐꜝꜜᴡԜᴐᴡԓͼꜛᴒᴑ꞉ᴐԜꞌͼᴑ꞉ᴟᴒᴐᴡꜝᴟԓͼԜꜜᴑͼꜛᴒᴑ꞉ᴐԜꞌͼꜛꜝꜜ꞉ᴡꜝᴟͼ꞉ꜜⱱꜝᴟꜛԜᴡ꞉ꜝꜜͼᴤԜᴠͼ
ᴢꜞᴑԜᴡᴒᴑͼᴤⱳᴒᴟᴒͼᴟᴒꞌᴒᴣԜꜜᴡ᷅

ꜚ꞉ꜜꜝᴟͼᴠꜞᴒꞌꞌ꞉ꜜⱲͼᴐⱳԜꜜⱲᴒͼᴤԜᴠͼꜛԜᴑᴒͼᴐⱳԜꜜⱲ꞉ꜜⱲͼᶰԜᴡⱳꜝᴢⱲⱳᶱͼᴡꜝͼᶰԜꞌᴡⱳꜝᴢⱲⱳ᷅ᶱ
Protocol Amendments
Summary of Change(s) Since Last Version of Approved Protocol
Amendment Number
2.0
Amendment Date
21 April 2016
Global/Country/Site 
Specific
Global
Description of Change
Section(s) Affected by 
Change
ᴀᴡԜᴡ꞉ᴠᴡ꞉ᴐԜꞌͼꜛᴒᴡⱳꜝᴑᴠͼᴤᴒᴟᴒͼᴢꜞᴑԜᴡᴒᴑͼᴡꜝͼᴢᴠᴒͼԜͼⱲᴒꜜᴒᴟԜꞌ꞉ᴧᴒᴑͼꞌ꞉ꜜᴒԜᴟͼꜛꜝᴑᴒꞌͼᴟԜᴡⱳᴒᴟͼᴡⱳԜꜜͼ
ⱲᴒꜜᴒᴟԜꞌ꞉ᴧᴒᴑͼᴒᴠᴡ꞉ꜛԜᴡ꞉ꜜⱲͼᴒꜟᴢԜᴡ꞉ꜝꜜͼꜛꜝᴑᴒꞌͼⱱꜝᴟͼᴡⱳᴒͼꜞᴟ꞉ꜛԜᴟᴦͼԜꜜԜꞌᴦᴠ꞉ᴠ᷅ͼᴁⱳ꞉ᴠͼᴢꜞᴑԜᴡᴒᴑͼ
ԜꜜԜꞌᴦᴠ꞉ᴠͼԜꜞꜞᴟꜝԜᴐⱳͼԜꞌᴠꜝͼԜꜞꜞꞌ꞉ᴒᴠͼᴡꜝͼᴡⱳᴒͼᴠᴒᴐꜝꜜᴑԜᴟᴦͼᴒꜜᴑꜞꜝ꞉ꜜᴡᴠ᷅ͼ
ᴀᴡᴢᴑᴦͼᴀᴦꜜꜝꜞᴠ꞉ᴠԓͼᴀᴡԜᴡ꞉ᴠᴡ꞉ᴐԜꞌͼ
ꜚᴒᴡⱳꜝᴑᴠ
ᴀᴀⱪꜛꜝꜜ꞉ᴡꜝᴟ꞉ꜜⱲͼᴟᴒꜞꞌԜᴐᴒᴑͼԝᴦͼⱫᴀꜚⱩⱢͼᴐꞌԜᴟ꞉ⱱ꞉ᴒᴑͼᴡⱳԜᴡͼꜜꜝͼ꞉ꜜᴡᴒᴟ꞉ꜛͼԜꜜԜꞌᴦᴠ꞉ᴠͼ꞉ᴠͼꜞꞌԜꜜꜜᴒᴑͼ
ⱱꜝᴟͼᴡⱳ꞉ᴠͼᴠᴡᴢᴑᴦ᷅
ᴀᴡᴢᴑᴦͼᴀᴦꜜꜝꜞᴠ꞉ᴠԓͼᴁⱳᴒͼ
ⱫᴀꜚⱩͼᴟᴒꜞꞌԜᴐᴒᴠͼᴡⱳᴒͼᴀᴀⱪ᷅
ⱨᴑᴑ꞉ᴡ꞉ꜝꜜͼᴡꜝͼԝᴒͼᴐꜝꜜᴠ꞉ᴠᴡᴒꜜᴡͼᴤ꞉ᴡⱳͼᴡⱳᴒͼⱬⱪⱵͼᴠᴐⱳᴒᴑᴢꞌᴒͼ꞉ꜜͼᴀᴒᴐᴡ꞉ꜝꜜͼⅎ᷅᷈ⅎԓͼⱴ꞉ꜜԜꞌͼⱴꜝꞌꞌꜝᴤ᷄ᴢꜞͼ
ᴃ꞉ᴠ꞉ᴡͼӿᴀᴢԝ꞊ᴒᴐᴡᴠͼꜜꜝᴡͼᴐꜝꜜᴡ꞉ꜜᴢ꞉ꜜⱲͼ꞉ꜜͼ꜡ꜞᴒꜜ᷄ꜙԜԝᴒꞌͼⱬᴥᴡᴒꜜᴠ꞉ꜝꜜͼᴀᴡᴢᴑᴦԐͼᴃ꞉ᴠ꞉ᴡ᷈⅍ԓͼ
ⱫԜᴦ᷊᷉˲ᶐ᷊ᴑԜᴦᴠ
ᴀᴡᴢᴑᴦͼⱨᴐᴡ꞉ᴣ꞉ᴡ꞉ᴒᴠͼᴀᴐⱳᴒᴑᴢꞌᴒͼ
ӿᴀᴦꜜꜝꜞᴠ꞉ᴠͼԜꜜᴑͼⱨꜞꜞᴒꜜᴑ꞉ᴥ᷈Ԑ
ᴂꜞᴑԜᴡᴒᴑͼᴡⱳᴒͼԜԝԝᴟᴒᴣ꞉Ԝᴡ꞉ꜝꜜͼꞌ꞉ᴠᴡͼԝԜᴠᴒᴑͼꜝꜜͼᴡⱳᴒͼᴐⱳԜꜜⱲᴒᴠͼᴡꜝͼᴡⱳᴒͼꜞᴟꜝᴡꜝᴐꜝꞌ᷅
ꜙ꞉ᴠᴡͼꜝⱱͼⱨԝԝᴟᴒᴣ꞉Ԝᴡ꞉ꜝꜜᴠ
ϸᴒꜞⱳᴟԜᴠᴒᴑͼⱱꜝᴟͼᴐꞌԜᴟ꞉ᴡᴦ᷅ͼᶰᴁꜝͼᴒᴣԜꞌᴢԜᴡᴒͼᴡⱳᴒͼᴒⱱⱱᴒᴐᴡͼꜝⱱͼⱫᴅ᷄᷉Ⱡ᷊᷇ͼꜝꜜͼⱳᴒԜꞌᴡⱳͼᴟᴒꞌԜᴡᴒᴑ
ꜟᴢԜꞌ꞉ᴡᴦͼꜝⱱͼꞌ꞉ⱱᴒͼӿϷꜝꜙԐᶱ
ᴀᴡᴢᴑᴦͼᴀᴦꜜꜝꜞᴠ꞉ᴠԓͼᴀᴒᴐᴡ꞉ꜝꜜͼ
᷊᷉᷅ԓͼᴁᴒᴟᴡ꞉Ԝᴟᴦͼ꜡ԝ꞊ᴒᴐᴡ꞉ᴣᴒᴠ
ϸᴒꜛꜝᴣᴒᴑͼᴡⱳᴒͼᴡᴒᴥᴡͼԜᴟꜝᴢꜜᴑͼᴟԜꜜᴑꜝꜛ꞉ᴧԜᴡ꞉ꜝꜜͼԝԜᴠᴒᴑͼꜝꜜͼꜜԜᵴᴣᴒͼᴣᴒᴟᴠᴢᴠͼꜜꜝꜜ᷄ꜜԜᵴᴣᴒͼᴠᴢԝ꞊ᴒᴐᴡᴠͼ
ᴡꜝͼԜꞌ꞉Ⱳꜜͼᴤ꞉ᴡⱳͼᴡⱳᴒͼꜜᴒᴤͼᴒᴥᴐꞌᴢᴠ꞉ꜝꜜͼᴐᴟ꞉ᴡᴒᴟ꞉ꜝꜜͼᴡꜝͼᴒᴥᴐꞌᴢᴑᴒͼᴠᴢԝ꞊ᴒᴐᴡᴠͼᴤⱳꜝͼꜛԜᴦͼⱳԜᴣᴒͼ
ꜞԜᴟᴡ꞉ᴐ꞉ꜞԜᴡᴒᴑͼ꞉ꜜͼԜͼꜞᴟ꞉ꜝᴟͼⱫᴅ᷄᷉Ⱡ᷊᷇
ᴀᴡᴢᴑᴦͼᴀᴦꜜꜝꜞᴠ꞉ᴠⱢͼᴀᴒᴐᴡ꞉ꜝꜜͼ
᷊᷊᷅᷈᷅᷈᷅ԓͼᴁᴟᴒԜᴡꜛᴒꜜᴡͼ͟ᴒᴟ꞉ꜝᴑⱢͼ
ᴀᴒᴐᴡ꞉ꜝꜜͼ⅍᷊᷅᷈ԓͼ
ϸԜꜜᴑꜝꜛ꞉ᴧԜᴡ꞉ꜝꜜ
ᴁⱳᴒͼꜞᴒᴟ꞉ꜝᴑͼⱱꜝᴟͼᴟᴒꜞꜝᴟᴡ꞉ꜜⱲͼⱶⱨⱬͼԜᴡᴡԜᴐꞋᴠͼԜⱱᴡᴒᴟͼᴡⱳᴒͼⱱ꞉ꜜԜꞌͼⱱꜝꞌꞌꜝᴤ᷄ᴢꜞͼᴣ꞉ᴠ꞉ᴡͼᴤԜᴠͼᴐꞌԜᴟ꞉ⱱ꞉ᴒᴑ᷅
ᴀᴡᴢᴑᴦͼᴀᴦꜜꜝꜞᴠ꞉ᴠⱢͼᴀᴒᴐᴡ꞉ꜝꜜͼ
᷊᷿᷅᷈᷅᷈᷅ԓͼⱴꜝꞌꞌꜝᴤ᷄ᴢꜞͼ͟ᴒᴟ꞉ꜝᴑ
ᴀᴀⱪͼꜛꜝꜜ꞉ᴡꜝᴟ꞉ꜜⱲͼᴟᴒꜞꞌԜᴐᴒᴑͼԝᴦͼⱫᴀꜚⱩ᷅
ᴀᴒᴐᴡ꞉ꜝꜜͼ᷊᷅᷈᷅᷉᷅᷈ԓͼⱷꜜᴡᴒᴟ꞉ꜛͼ
ⱨꜜԜꞌᴦᴠ꞉ᴠͼԜꜜᴑͼⱫԜᴡԜͼᴀԜⱱᴒᴡᴦͼ
ꜚꜝꜜ꞉ᴡꜝᴟ꞉ꜜⱲͼⱩꜝԜᴟᴑͼӿⱫᴀꜚⱩԐ
ᴁᴒᴥᴡͼᴢꜞᴑԜᴡᴒᴑͼᴡꜝͼᴟᴒⱱꞌᴒᴐᴡͼᴡⱳᴒͼᴒᴥᴐꞌᴢᴠ꞉ꜝꜜͼꜝⱱͼᴠᴢԝ꞊ᴒᴐᴡᴠͼᴤⱳꜝͼꜛԜᴦͼⱳԜᴣᴒͼꜞԜᴟᴡ꞉ᴐ꞉ꜞԜᴡᴒᴑͼ꞉ꜜͼԜͼ
ꜞᴟ꞉ꜝᴟͼⱫᴅ᷄᷉Ⱡ᷊᷇ͼᴠᴡᴢᴑᴦ
ᴀᴡᴢᴑᴦͼᴀᴦꜜꜝꜞᴠ꞉ᴠⱢͼᴀᴒᴐᴡ꞉ꜝꜜͼ
᷾᷅᷈ԓͼᴀᴡᴢᴑᴦͼ͟ꜝꜞᴢꞌԜᴡ꞉ꜝꜜ
ᴁᴒᴥᴡͼᴢꜞᴑԜᴡᴒᴑͼᴡꜝͼᴟᴒⱱꞌᴒᴐᴡͼᴡⱳᴒͼᴒᴥᴐꞌᴢᴠ꞉ꜝꜜͼꜝⱱͼᴠᴢԝ꞊ᴒᴐᴡᴠͼᴤⱳꜝͼꜛԜᴦͼⱳԜᴣᴒͼꜞԜᴟᴡ꞉ᴐ꞉ꜞԜᴡᴒᴑͼ꞉ꜜͼԜͼ
ꜞᴟ꞉ꜝᴟͼⱫᴅ᷄᷉Ⱡ᷊᷇ͼᴠᴡᴢᴑᴦ
ᴀᴡᴢᴑᴦͼᴀᴦꜜꜝꜞᴠ꞉ᴠⱢͼᴀᴒᴐᴡ꞉ꜝꜜͼ
᷾᷅᷉ԓͼⱪᴟ꞉ᴡᴒᴟ꞉Ԝͼⱱꜝᴟͼⱷꜜᴐꞌᴢᴠ꞉ꜝꜜ

Ⱬᴅ᷄᷉Ⱡ᷊᷇
ⱪꞌ꞉ꜜ꞉ᴐԜꞌͼᴁᴟ꞉Ԝꞌͼ͟ᴟꜝᴡꜝᴐꜝꞌⱡͼⱫᴅ᷄᷉Ⱡ᷊᷊᷇᷄᷇
ⱨꜛᴒꜜᴑꜛᴒꜜᴡͼ᷊᷅᷇ͼⱴ꞉ꜜԜꞌⱡͼ᷇ⱠͼꜗԜꜜᴢԜᴟᴦͼ᷉᷇᷈ⅎ
ⱪꜝꜜⱱ꞉ᴑᴒꜜᴡ꞉Ԝꞌ
͟ԜⱲᴒͼⱠⅎ
ⱫᴦԜᴥͼⱪꜝᴟꜞ᷅
Protocol Amendments
Summary of Change(s) Since Last Version of Approved Protocol
Amendment Number
2.0
Amendment Date
21 April 2016
Global/Country/Site 
Specific
Global
Description of Change
Section(s) Affected by 
Change
ᴀ꞉ꜜᴐᴒͼꜜꜝͼᴑԜᴡԜͼꜝꜜͼᴒꜛԝᴟᴦꜝ᷄ⱱᴒᴡԜꞌͼᴑᴒᴣᴒꞌꜝꜞꜛᴒꜜᴡͼᴡꜝᴥ꞉ᴐ꞉ᴡᴦͼԜᴟᴒͼԜᴣԜ꞉ꞌԜԝꞌᴒԓͼꜞᴒᴟͼᴡⱳᴒͼᴐꞌ꞉ꜜ꞉ᴐԜꞌͼ
ᴡᴟ꞉ԜꞌͼⱱԜᴐ꞉ꞌ꞉ᴡԜᴡ꞉ꜝꜜͼⱲᴟꜝᴢꜞᶳᴠͼӿⱪᴁⱴⱵԐͼᴟᴒᴐꜝꜛꜛᴒꜜᴑԜᴡ꞉ꜝꜜᴠͼᴟᴒꞌԜᴡᴒᴑͼᴡꜝͼᴐꜝꜜᴡᴟԜᴐᴒꜞᴡ꞉ꜝꜜͼԜꜜᴑͼ
ꜞᴟᴒⱲꜜԜꜜᴐᴦͼᴡᴒᴠᴡ꞉ꜜⱲͼ꞉ꜜͼᴐꞌ꞉ꜜ꞉ᴐԜꞌͼᴡᴟ꞉Ԝꞌᴠԓͼⱳ꞉Ⱳⱳᴒᴠᴡͼᴟ꞉ᴠꞋͼ꞉ᴠͼԜᴠᴠᴢꜛᴒᴑ᷅ͼᴁⱳᴒᴟᴒⱱꜝᴟᴒԓͼᴡⱳᴒͼ
꞉ꜜᴐꞌᴢᴠ꞉ꜝꜜͼᴐᴟ꞉ᴡᴒᴟ꞉ꜝꜜͼⱱꜝᴟͼᴐꜝꜜᴡᴟԜᴐᴒꜞᴡ꞉ꜝꜜͼᴟᴒꜟᴢ꞉ᴟᴒꜛᴒꜜᴡᴠͼᴤԜᴠͼꜛꜝᴑ꞉ⱱ꞉ᴒᴑͼᴡꜝͼᴒꜛꜞⱳԜᴠ꞉ᴧᴒͼᴡⱳᴒͼ
ᴢᴠᴒͼꜝⱱͼⱳ꞉Ⱳⱳꞌᴦͼᴒⱱⱱᴒᴐᴡ꞉ᴣᴒͼᴐꜝꜜᴡᴟԜᴐᴒꜞᴡ꞉ᴣᴒͼꜛᴒԜᴠᴢᴟᴒᴠͼᴑᴢᴟ꞉ꜜⱲͼᴡᴟᴒԜᴡꜛᴒꜜᴡͼԜꜜᴑͼᴢꜜᴡ꞉ꞌͼᴡⱳᴒͼᴒꜜᴑͼ
ꜝⱱͼᴟᴒꞌᴒᴣԜꜜᴡͼᴠᴦᴠᴡᴒꜛ꞉ᴐͼᴒᴥꜞꜝᴠᴢᴟᴒͼⱱꜝᴟͼᴤꜝꜛᴒꜜͼꜝⱱͼᴐⱳ꞉ꞌᴑͼԝᴒԜᴟ꞉ꜜⱲͼꜞꜝᴡᴒꜜᴡ꞉ԜꞌⱢͼⱷᴡͼᴤԜᴠͼԜꞌᴠꜝͼ
ᴐꞌԜᴟ꞉ⱱ꞉ᴒᴑͼᴡⱳԜᴡͼᴡⱳᴒͼᴢᴠᴒͼꜝⱱͼԜͼꜛԜꞌᴒͼᴐꜝꜜᴑꜝꜛͼᴤ꞉ᴡⱳͼꜝᴟͼᴤ꞉ᴡⱳꜝᴢᴡͼᴠꜞᴒᴟꜛ꞉ᴐ꞉ᴑᴒͼꜝᴟͼᴐᴒᴟᴣ꞉ᴐԜꞌͼ
ᴐԜꜞԓͼᴑ꞉ԜꜞⱳᴟԜⱲꜛͼꜝᴟͼᴠꜞꜝꜜⱲᴒͼᴤ꞉ᴡⱳͼᴠꜞᴒᴟꜛ꞉ᴐ꞉ᴑᴒͼꜝᴟͼԜͼᴐꜝꜛԝ꞉ꜜԜᴡ꞉ꜝꜜͼӿᴑꜝᴢԝꞌᴒͼԝԜᴟᴟ꞉ᴒᴟͼ
ꜛᴒᴡⱳꜝᴑᴠԐͼ꞉ᴠͼꜜꜝᴡͼᴐꜝꜜᴠ꞉ᴑᴒᴟᴒᴑͼⱳ꞉Ⱳⱳꞌᴦͼᴒⱱⱱᴒᴐᴡ꞉ᴣᴒ᷅
ᴀᴡᴢᴑᴦͼᴀᴦꜜꜝꜞᴠ꞉ᴠⱢ
ᴀᴒᴐᴡ꞉ꜝꜜͼ᷾᷅᷉ԓͼⱪᴟ꞉ᴡᴒᴟ꞉Ԝͼⱱꜝᴟͼ
ⱷꜜᴐꞌᴢᴠ꞉ꜝꜜ
ⱨᴑᴑᴒᴑͼԜͼꜜᴒᴤͼᴒᴥᴐꞌᴢᴠ꞉ꜝꜜͼᴐᴟ꞉ᴡᴒᴟ꞉ꜝꜜͼᴡꜝͼᴒᴥᴐꞌᴢᴑᴒͼᴠᴢԝ꞊ᴒᴐᴡᴠͼᴤⱳꜝͼꜛԜᴦͼⱳԜᴣᴒͼꜞԜᴟᴡ꞉ᴐ꞉ꜞԜᴡᴒᴑͼ
꞉ꜜͼԜͼꜞᴟ꞉ꜝᴟͼⱫᴅ᷄᷉Ⱡ᷊᷇ͼᴠᴡᴢᴑᴦͼ꞉ꜜͼꜝᴟᴑᴒᴟͼᴡꜝͼᴒꞌ꞉ꜛ꞉ꜜԜᴡᴒͼꜜꜝꜜ᷄ꜜԜᵴᴣᴒͼⱱᴟꜝꜛͼᴡⱳ꞉ᴠͼᴠᴡᴢᴑᴦ᷅ⱨꞌᴠꜝԓͼ
ᴡⱳᴒͼꜝᴡⱳᴒᴟͼᴒᴥᴐꞌᴢᴠ꞉ꜝꜜͼᴐᴟ꞉ᴡᴒᴟ꞉Ԝͼᴤᴒᴟᴒͼᴟᴒꜜᴢꜛԝᴒᴟᴒᴑ
ᴀᴡᴢᴑᴦͼᴀᴦꜜꜝꜞᴠ꞉ᴠⱢͼᴀᴒᴐᴡ꞉ꜝꜜͼ
᷊᷾᷅ԓͼⱬᴥᴐꞌᴢᴠ꞉ꜝꜜͼⱪᴟ꞉ᴡᴒᴟ꞉Ԝ
ⱪꞌԜᴟ꞉ⱱ꞉ᴒᴠͼᴢꜜԝꞌ꞉ꜜᴑ꞉ꜜⱲͼꜞᴟꜝᴐᴒᴑᴢᴟᴒᴠ᷅
ᴀᴒᴐᴡ꞉ꜝꜜͼ᷿᷅᷾ԓͼⱩꞌ꞉ꜜᴑ꞉ꜜⱲͼԜꜜᴑͼ
ᴂꜜԝꞌ꞉ꜜᴑ꞉ꜜⱲ
ⱴꜝᴟͼᴡⱳᴒͼꜛԜꜜԜⱲᴒꜛᴒꜜᴡͼꜝⱱͼԜᴐᴢᴡᴒͼⱶⱨⱬͼԜᴡᴡԜᴐꞋᴠԓͼ꞉ᴡͼᴤԜᴠͼᴐꞌԜᴟ꞉ⱱ꞉ᴒᴑͼᴡⱳԜᴡͼԜᴑꜛ꞉ꜜ꞉ᴠᴡᴟԜᴡ꞉ꜝꜜͼꜝⱱͼ
ᴡⱳᴒͼ꞉ꜜᴣᴒᴠᴡ꞉ⱲԜᴡ꞉ꜝꜜԜꞌͼꜞᴟꜝᴑᴢᴐᴡͼԜꜜᴑͼᴠᴡᴢᴑᴦͼꜞᴟꜝᴐᴒᴑᴢᴟᴒᴠͼᴤ꞉ꞌꞌͼᴐꜝꜜᴡ꞉ꜜᴢᴒͼᴤ꞉ᴡⱳꜝᴢᴡͼԜꞌᴡᴒᴟԜᴡ꞉ꜝꜜͼ
ᴡꜝͼᴡⱳᴒͼꜞᴟꜝᴡꜝᴐꜝꞌͼᴠꜞᴒᴐ꞉ⱱ꞉ᴒᴑͼᴠᴡᴢᴑᴦͼᴠᴐⱳᴒᴑᴢꞌᴒԓͼᴒᴣᴒꜜͼ꞉ⱱͼᴡⱳᴒͼꜞԜᴡ꞉ᴒꜜᴡͼᴟᴒᴐᴒ꞉ᴣᴒᴠͼԜꜜᴦͼᴡᴟᴒԜᴡꜛᴒꜜᴡͼ
ⱱꜝᴟͼԜꜜͼⱶⱨⱬͼԜᴡᴡԜᴐꞋ᷅
ᴀᴡᴢᴑᴦͼᴀᴦꜜꜝꜞᴠ꞉ᴠԓͼⱶⱨⱬͼ
ⱨᴡᴡԜᴐꞋͼꜚԜꜜԜⱲᴒꜛᴒꜜᴡԐⱢͼ
ᴀᴒᴐᴡ꞉ꜝꜜͼ᷿᷿᷅᷅᷈ԓͼⱨꞌꞌꜝᴤᴒᴑͼ
ᴁⱳᴒᴟԜꜞ꞉ᴒᴠ
ⱫᴦԜᴥͼᴟᴒꜞꞌԜᴐᴒᴑͼᴤ꞉ᴡⱳͼᴡⱳᴒͼⱲᴒꜜᴒᴟԜꞌͼᴡᴒᴟꜛͼᶰᴀꜞꜝꜜᴠꜝᴟᶱͼᴡⱳᴟꜝᴢⱲⱳꜝᴢᴡͼᴡⱳᴒͼꜞᴟꜝᴡꜝᴐꜝꞌ᷅ͼ
ᴀᴒᴐᴡ꞉ꜝꜜͼ᷿᷅˲ԓͼ͟ԜᴐꞋԜⱲ꞉ꜜⱲͼԜꜜᴑͼ
ꜙԜԝᴒꞌ꞉ꜜⱲⱢͼᴀᴒᴐᴡ꞉ꜝꜜͼ⅍᷅᷈⅍᷅᷈᷅⅍ԓͼ
ⱨᴑᴣᴒᴟᴠᴒͼⱬᴣᴒꜜᴡᴠͼꜝⱱͼᴀꜞᴒᴐ꞉Ԝꞌͼ
ⱷꜜᴡᴒᴟᴒᴠᴡⱢͼᴀᴒᴐᴡ꞉ꜝꜜͼ⅍᷅᷈⅍᷊᷊᷅᷅ԓͼ
ⱨᴠᴠᴒᴠᴠꜛᴒꜜᴡͼꜝⱱͼⱪꞌ꞉ꜜ꞉ᴐԜꞌͼ
ᴀ꞉Ⱳꜜ꞉ⱱ꞉ᴐԜꜜᴐᴒͼӿԜꜜᴑͼᴤⱳᴒᴟᴒᴣᴒᴟͼ
ᴟᴒꞌᴒᴣԜꜜᴡͼᴒᴥᴐᴒꜞᴡͼᴡⱳᴒͼᴡ꞉ᴡꞌᴒͼ
ꜞԜⱲᴒԓͼⱱ꞉ᴟᴠᴡͼᴟꜝᴤͼꜝⱱͼᴡⱳᴒͼᴀᴡᴢᴑᴦͼ
ᴀᴦꜜꜝꜞᴠ꞉ᴠԓͼԜꜜᴑͼᴁԜԝꞌᴒͼ᷉ͼ꞉ꜜͼ
ᴀᴒᴐᴡ꞉ꜝꜜͼ᷈᷇ͼᴈⱬᴢᴟꜝꜞᴒͼ
ꜛꜝꜜ꞉ᴡꜝᴟ꞉ꜜⱲͼᴟᴒᴠꜞꜝꜜᴠ꞉ԝ꞉ꞌ꞉ᴡᴦᴊԐ

Ⱬᴅ᷄᷉Ⱡ᷊᷇
ⱪꞌ꞉ꜜ꞉ᴐԜꞌͼᴁᴟ꞉Ԝꞌͼ͟ᴟꜝᴡꜝᴐꜝꞌⱡͼⱫᴅ᷄᷉Ⱡ᷊᷊᷇᷄᷇
ⱨꜛᴒꜜᴑꜛᴒꜜᴡͼ᷊᷅᷇ͼⱴ꞉ꜜԜꞌⱡͼ᷇ⱠͼꜗԜꜜᴢԜᴟᴦͼ᷉᷇᷈ⅎ
ⱪꜝꜜⱱ꞉ᴑᴒꜜᴡ꞉Ԝꞌ
͟ԜⱲᴒͼⱠ˲
ⱫᴦԜᴥͼⱪꜝᴟꜞ᷅
Protocol Amendments
Summary of Change(s) Since Last Version of Approved Protocol
Amendment Number
2.0
Amendment Date
21 April 2016
Global/Country/Site 
Specific
Global
Description of Change
Section(s) Affected by 
Change
ᴁⱳᴒͼᴒⱱⱱ꞉ᴐԜᴐᴦͼᴒᴣԜꞌᴢԜᴡ꞉ꜝꜜͼꜞᴒᴟ꞉ꜝᴑͼᴢꜞᴑԜᴡᴒᴑͼⱱᴟꜝꜛͼⱫԜᴦͼ᷇ͼᴡꜝͼⱫԜᴦͼ᷈᷾ͼᴡꜝͼԝᴒͼᴐꜝꜜᴠ꞉ᴠᴡᴒꜜᴡͼ
ᴤ꞉ᴡⱳͼᴡⱳᴒͼ꞉ꜜᴡᴒꜜᴡ᷄ᴡꜝ᷄ᴡᴟᴒԜᴡͼԜꜜԜꞌᴦᴠ꞉ᴠͼꜞᴟ꞉ꜜᴐ꞉ꜞꞌᴒ᷅ͼ
ᴁⱳᴒͼᴑᴒᴠᴐᴟ꞉ꜞᴡ꞉ꜝꜜͼꜝⱱͼᴡⱳᴒͼꜞᴟ꞉ꜛԜᴟᴦͼᴒꜜᴑꜞꜝ꞉ꜜᴡͼᴤԜᴠͼꜛꜝᴑ꞉ⱱ꞉ᴒᴑͼⱱꜝᴟͼԜᴠᴠᴒᴠᴠꜛᴒꜜᴡͼᴑᴢᴟ꞉ꜜⱲͼᴡⱳᴒͼ
ᴒⱱⱱ꞉ᴐԜᴐᴦͼᴒᴣԜꞌᴢԜᴡ꞉ꜝꜜͼꜞᴒᴟ꞉ꜝᴑͼᴟԜᴡⱳᴒᴟͼᴡⱳԜꜜͼꜞᴒᴟͼᴤᴒᴒꞋͼⱱꜝᴟͼᴐꜝꜜᴠ꞉ᴠᴡᴒꜜᴐᴦͼᴤ꞉ᴡⱳͼᴡⱳᴒͼᴠᴡԜᴡ꞉ᴠᴡ꞉ᴐԜꞌͼ
ꜛꜝᴑᴒꞌ᷅ͼ
ᴁⱳᴒͼᴠᴒᴐꜝꜜᴑԜᴟᴦͼᴒꜜᴑꜞꜝ꞉ꜜᴡͼᶰᴁ꞉ꜛᴒͼᴡꜝͼⱱ꞉ᴟᴠᴡͼԜᴡᴡԜᴐꞋԓͼ꞉᷅ᴒ᷅ԓͼᴑᴢᴟԜᴡ꞉ꜝꜜͼᴡⱳԜᴡͼԜͼᴠᴢԝ꞊ᴒᴐᴡͼ꞉ᴠͼ
ԜᴡᴡԜᴐꞋ᷄ⱱᴟᴒᴒͼᴢꜜᴡ꞉ꞌͼᴡⱳᴒ꞉ᴟͼⱱ꞉ᴟᴠᴡͼԜᴡᴡԜᴐꞋᶱͼᴤԜᴠͼᴟᴒꜛꜝᴣᴒᴑͼⱱᴟꜝꜛͼᴡⱳᴒͼᴟԜꜜꞋͼꜝᴟᴑᴒᴟͼԜꜜᴑͼᴤ꞉ꞌꞌͼԝᴒͼ
ᴐꜝꜜᴠ꞉ᴑᴒᴟᴒᴑͼԜꜜͼᴒᴥꜞꞌꜝᴟԜᴡꜝᴟᴦͼᴒꜜᴑꜞꜝ꞉ꜜᴡ᷅ͼⱷᴡͼᴤԜᴠͼꜛꜝᴑ꞉ⱱ꞉ᴒᴑͼᴡꜝͼᶰᴁ꞉ꜛᴒͼᴡꜝͼⱱ꞉ᴟᴠᴡͼⱶⱨⱬͼԜᴡᴡԜᴐꞋͼ
ԜⱱᴡᴒᴟͼⱫԜᴦͼ᷈᷾ԓͼ꞉᷅ᴒ᷅ԓͼᴑᴢᴟԜᴡ꞉ꜝꜜͼᴡⱳԜᴡͼԜͼᴠᴢԝ꞊ᴒᴐᴡͼ꞉ᴠͼԜᴡᴡԜᴐꞋ᷄ⱱᴟᴒᴒͼԜⱱᴡᴒᴟͼⱫԜᴦͼ᷈᷾ᶱͼᴡꜝͼԜꞌꞌꜝᴤͼ
ᴒꜜꜝᴢⱲⱳͼᴡ꞉ꜛᴒͼᴡꜝͼⱱ꞉ᴟᴠᴡͼԜᴡᴡԜᴐꞋͼⱱꜝᴟͼᴡⱳ꞉ᴠͼᴒꜜᴑꜞꜝ꞉ꜜᴡͼԜᴠᴠᴒᴠᴠꜛᴒꜜᴡ᷅
ᴁⱳᴒͼᴠᴒᴐꜝꜜᴑԜᴟᴦͼᴒꜜᴑꜞꜝ꞉ꜜᴡͼᶰ꜠ᴢꜛԝᴒᴟͼꜝⱱͼⱳ꞉Ⱳⱳ᷄ꜛꜝᴟԝ꞉ᴑ꞉ᴡᴦͼⱶⱨⱬͼԜᴡᴡԜᴐꞋᴠᶱͼᴟᴒꜛꜝᴣᴒᴑͼⱱᴟꜝꜛͼ
ᴡⱳᴒͼᴟԜꜜꞋͼꜝᴟᴑᴒᴟͼԜꜜᴑͼᴤ꞉ꞌꞌͼԝᴒͼᴐꜝꜜᴠ꞉ᴑᴒᴟᴒᴑͼԜꜜͼᴒᴥꜞꞌꜝᴟԜᴡꜝᴟᴦͼᴒꜜᴑꜞꜝ꞉ꜜᴡ᷅
ᴁⱳᴒͼᴑᴒᴠᴐᴟ꞉ꜞᴡ꞉ꜝꜜͼꜝⱱͼᴡⱳᴒͼᴠᴒᴐꜝꜜᴑԜᴟᴦͼᴒꜜᴑꜞꜝ꞉ꜜᴡᴠͼᴤԜᴠͼꜛꜝᴑ꞉ⱱ꞉ᴒᴑͼⱱꜝᴟͼԜᴠᴠᴒᴠᴠꜛᴒꜜᴡͼᴑᴢᴟ꞉ꜜⱲͼ
ᴡⱳᴒͼᴒⱱⱱ꞉ᴐԜᴐᴦͼᴒᴣԜꞌᴢԜᴡ꞉ꜝꜜꜞᴒᴟ꞉ꜝᴑͼᴟԜᴡⱳᴒᴟͼᴡⱳԜꜜͼꜞᴒᴟͼᴤᴒᴒꞋͼⱱꜝᴟͼᴐꜝꜜᴠ꞉ᴠᴡᴒꜜᴐᴦͼᴤ꞉ᴡⱳͼᴡⱳᴒͼ
ᴠᴡԜᴡ꞉ᴠᴡ꞉ᴐԜꞌͼꜛꜝᴑᴒꞌ᷅ͼᴁⱳᴒͼᴢꜜ꞉ᴡͼꜝⱱͼꜛᴒԜᴠᴢᴟᴒꜛᴒꜜᴡͼ꞉ᴠͼ꞉ᴟᴟᴒꞌᴒᴣԜꜜᴡͼⱱꜝᴟͼᴡⱳᴒͼᴠᴡԜᴡ꞉ᴠᴡ꞉ᴐԜꞌͼꜛꜝᴑᴒꞌͼԜᴠͼ
ᴡⱳᴒͼⱳᴦꜞꜝᴡⱳᴒᴠ꞉ᴠͼᴡᴒᴠᴡͼ꞉ᴠͼԝԜᴠᴒᴑͼꜝꜜͼᴡⱳᴒͼᴟԜᴡᴒͼᴟԜᴡ꞉ꜝ᷅ͼϸᴒᴠᴢꞌᴡᴠͼⱱᴟꜝꜛͼᴡⱳᴒͼᴠᴡԜᴡ꞉ᴠᴡ꞉ᴐԜꞌͼꜛꜝᴑᴒꞌͼ
ᴤ꞉ꞌꞌͼԝᴒͼᴟᴒꜞꜝᴟᴡᴒᴑͼ꞉ꜜͼԝꜝᴡⱳͼᴤᴒᴒꞋᴠͼԜꜜᴑͼꜛꜝꜜᴡⱳᴠͼᴡꜝͼⱱԜᴐ꞉ꞌ꞉ᴡԜᴡᴒͼᴐꞌ꞉ꜜ꞉ᴐԜꞌͼ꞉ꜜᴡᴒᴟꜞᴟᴒᴡԜᴡ꞉ꜝꜜ᷅
ᴀᴡᴢᴑᴦͼᴀᴦꜜꜝꜞᴠ꞉ᴠԓͼⱪᴟ꞉ᴡᴒᴟ꞉Ԝͼ
ⱱꜝᴟͼⱬᴣԜꞌᴢԜᴡ꞉ꜝꜜⱢͼᴀᴒᴐᴡ꞉ꜝꜜͼ
⅍᷅᷾᷅᷈ԓͼ͟ᴟ꞉ꜛԜᴟᴦͼԜꜜᴑͼ
ᴀᴒᴐꜝꜜᴑԜᴟᴦͼⱬꜜᴑꜞꜝ꞉ꜜᴡᴠ
ⱴꜝᴟͼᴡⱳᴒͼᴐꜝꞌꞌᴒᴐᴡ꞉ꜝꜜͼꜝⱱͼⱶⱨⱬͼԜᴡᴡԜᴐꞋͼᴑԜᴡԜԓͼ꞉ᴡͼᴤԜᴠͼᴐꞌԜᴟ꞉ⱱ꞉ᴒᴑͼᴡⱳԜᴡͼᴤᴒᴒꞋꞌᴦͼᴐꜝꜛꜛᴢꜜ꞉ᴐԜᴡ꞉ꜝꜜͼ
ԝᴒᴡᴤᴒᴒꜜͼᴡⱳᴒͼꜞԜᴡ꞉ᴒꜜᴡᴠͼԜꜜᴑͼᴡⱳᴒͼᴠ꞉ᴡᴒԓͼ꞉ꜜᴐꞌᴢᴑ꞉ꜜⱲͼᴟᴒꜞꜝᴟᴡᴠͼꜝⱱͼⱶⱨⱬͼԜᴡᴡԜᴐꞋᴠԓͼꜛᴢᴠᴡͼԝᴒͼ
ᴑꜝᴐᴢꜛᴒꜜᴡᴒᴑͼ꞉ꜜͼᴡⱳᴒͼᴒⱪϸⱴ᷅
ᴀᴡᴢᴑᴦͼᴀᴦꜜꜝꜞᴠ꞉ᴠԓͼⱪꜝꞌꞌᴒᴐᴡ꞉ꜝꜜͼ
ꜝⱱͼⱶⱨⱬͼⱨᴡᴡԜᴐꞋͼⱫԜᴡԜⱢͼ
ᴀᴒᴐᴡ꞉ꜝꜜͼ⅍᷅᷾᷅᷉᷅ͼⱶⱨⱬͼⱨᴡᴡԜᴐꞋͼ
ⱷꜜⱱꜝᴟꜛԜᴡ꞉ꜝꜜͼⱪꜝꞌꞌᴒᴐᴡ꞉ꜝꜜ
ϸᴒꜛꜝᴣᴒᴑͼᴡ꞉ꜛᴒͼԝꜝᴢꜜᴑͼꜝⱱͼⅎͼᴑԜᴦᴠ᷅
ᴀᴡᴢᴑᴦͼᴀᴦꜜꜝꜞᴠ꞉ᴠԓͼⱪꜝꞌꞌᴒᴐᴡ꞉ꜝꜜͼ
ꜝⱱͼⱶⱨⱬͼⱨᴡᴡԜᴐꞋͼⱫԜᴡԜⱢͼ
ᴀᴒᴐᴡ꞉ꜝꜜͼ⅍᷅᷾᷅᷉ԓͼⱶⱨⱬͼⱨᴡᴡԜᴐꞋͼ
ⱷꜜⱱꜝᴟꜛԜᴡ꞉ꜝꜜͼⱪꜝꞌꞌᴒᴐᴡ꞉ꜝꜜ
ᴁᴒᴥᴡͼᴢꜞᴑԜᴡᴒᴑͼᴡꜝͼᴟᴒⱱꞌᴒᴐᴡͼᴡⱳᴒͼᴒᴥᴐꞌᴢᴠ꞉ꜝꜜͼꜝⱱͼᴠᴢԝ꞊ᴒᴐᴡᴠͼᴤⱳꜝͼꜛԜᴦͼⱳԜᴣᴒͼꜞԜᴟᴡ꞉ᴐ꞉ꜞԜᴡᴒᴑͼ꞉ꜜͼԜͼ
ꜞᴟ꞉ꜝᴟͼⱫᴅ᷄᷉Ⱡ᷊᷇ͼᴠᴡᴢᴑᴦ᷅
ᴀᴡᴢᴑᴦͼᴀᴦꜜꜝꜞᴠ꞉ᴠⱢͼᴀᴡᴢᴑᴦͼ
ⱨᴐᴡ꞉ᴣ꞉ᴡ꞉ᴒᴠͼᴀᴐⱳᴒᴑᴢꞌᴒͼ
ӿⱴꜝꜝᴡꜜꜝᴡᴒͼ⅍ԐⱢͼᴀᴒᴐᴡ꞉ꜝꜜͼ
⅍᷅˲᷅᷈᷅ⅎԓͼⱪ᷈᷄ⱷ꜠ⱶͼ
ⱴᴢꜜᴐᴡ꞉ꜝꜜԜꞌͼⱨᴠᴠԜᴦⱢͼᴀᴒᴐᴡ꞉ꜝꜜͼ
⅍᷅˲᷅᷈᷅˲ԓͼⱪ᷾ͼⱨᴠᴠԜᴦⱢͼᴀᴒᴐᴡ꞉ꜝꜜͼ
⅍᷅˲᷅᷈᷅Ⱡԓͼⱪ᷈ꜟͼⱨᴠᴠԜᴦ
ⱨᴑᴑᴒᴑͼԜᴑᴑ꞉ᴡ꞉ꜝꜜԜꞌͼⱨꜜⱲ꞉ꜝᴒᴑᴒꜛԜ᷄ϷᴢԜꞌ꞉ᴡᴦͼꜝⱱͼꜙ꞉ⱱᴒͼӿⱨⱬ᷄ϷꜝꜙԐͼϷᴢᴒᴠᴡ꞉ꜝꜜꜜԜ꞉ᴟᴒͼ
ԜᴠᴠᴒᴠᴠꜛᴒꜜᴡᴠͼꜝꜜͼⱫԜᴦᴠͼ᷉˲ᶐ᷊ԓͼ᷿⅍ᶐ᷊ԓͼ᷈᷉⅍ᶐ᷊ԓͼԜꜜᴑͼ᷿᷈᷾ᶐ᷊ͼⱱꜝᴟͼԜͼԝᴒᴡᴡᴒᴟͼꜛᴒԜᴠᴢᴟᴒͼԜꜜᴑͼ
ᴐꜝꜛꜞԜᴟ꞉ᴠꜝꜜͼꜝⱱͼᴑԜᴡԜͼԜᴣԜ꞉ꞌԜԝꞌᴒͼⱱᴟꜝꜛͼᴡⱳ꞉ᴠͼᴠᴡᴢᴑᴦ᷅ͼ
ᴀᴦꜜꜝꜞᴠ꞉ᴠⱢͼᴀᴡᴢᴑᴦͼⱨᴐᴡ꞉ᴣ꞉ᴡ꞉ᴒᴠͼ
ᴀᴐⱳᴒᴑᴢꞌᴒⱢͼᴀᴒᴐᴡ꞉ꜝꜜͼ⅍᷿᷅᷈ԓͼ
ϷᴢԜꞌ꞉ᴡᴦͼꜝⱱͼꜙ꞉ⱱᴒͼ
ⱨᴠᴠᴒᴠᴠꜛᴒꜜᴡᴠⱢͼᴀᴒᴐᴡ꞉ꜝꜜⱠ᷅᷈᷈ԓͼ
ⱨꜜԜꞌᴦᴠ꞉ᴠͼꜝⱱͼϷᴢԜꞌ꞉ᴡᴦͼꜝⱱͼꜙ꞉ⱱᴒͼ
ⱨᴠᴠᴒᴠᴠꜛᴒꜜᴡᴠ
ᴀᴀⱪͼᴟᴒꜞꞌԜᴐᴒᴑͼᴤ꞉ᴡⱳͼⱫᴀꜚⱩ
ᴀᴒᴐᴡ꞉ꜝꜜͼ⅍᷅᷈⅍᷊᷊᷅᷅ԓͼ
ⱨᴠᴠᴒᴠᴠꜛᴒꜜᴡͼꜝⱱͼⱪꞌ꞉ꜜ꞉ᴐԜꞌͼ
ᴀ꞉Ⱳꜜ꞉ⱱ꞉ᴐԜꜜᴐᴒ
ᴂꜞᴑԜᴡᴒᴑͼᴐꜝꜜᴡԜᴐᴡᴠ
ᴀᴒᴐᴡ꞉ꜝꜜͼ⅍᷅᷈⅍᷿᷿᷅᷅ԓͼᴀԜⱱᴒᴡᴦͼ
ⱪꜝꜜᴡԜᴐᴡͼⱷꜜⱱꜝᴟꜛԜᴡ꞉ꜝꜜͼ

Ⱬᴅ᷄᷉Ⱡ᷊᷇
ⱪꞌ꞉ꜜ꞉ᴐԜꞌͼᴁᴟ꞉Ԝꞌͼ͟ᴟꜝᴡꜝᴐꜝꞌⱡͼⱫᴅ᷄᷉Ⱡ᷊᷊᷇᷄᷇
ⱨꜛᴒꜜᴑꜛᴒꜜᴡͼ᷊᷅᷇ͼⱴ꞉ꜜԜꞌⱡͼ᷇ⱠͼꜗԜꜜᴢԜᴟᴦͼ᷉᷇᷈ⅎ
ⱪꜝꜜⱱ꞉ᴑᴒꜜᴡ꞉Ԝꞌ
͟ԜⱲᴒͼⱠⱠ
ⱫᴦԜᴥͼⱪꜝᴟꜞ᷅
Protocol Amendments
Summary of Change(s) Since Last Version of Approved Protocol
Amendment Number
2.0
Amendment Date
21 April 2016
Global/Country/Site 
Specific
Global
Description of Change
Section(s) Affected by 
Change
ᴁⱳᴟꜝᴢⱲⱳꜝᴢᴡͼᴡⱳᴒꜞᴟꜝᴡꜝᴐꜝꞌԓͼԜᴠͼ꞉ꜜͼᴡⱳ꞉ᴠͼᴠᴒᴐᴡ꞉ꜝꜜԓͼⱫᴦԜᴥͼᴤԜᴠͼᴟᴒꜞꞌԜᴐᴒᴑͼԝᴦͼᶰᴡⱳᴒͼᴀꜞꜝꜜᴠꜝᴟ᷅ᶱ
ᴀᴒᴐᴡ꞉ꜝꜜͼ⅍᷅᷈⅍᷅᷈᷅⅍ԓͼⱨᴑᴣᴒᴟᴠᴒͼ
ⱬᴣᴒꜜᴡᴠͼꜝⱱͼᴀꜞᴒᴐ꞉Ԝꞌͼⱷꜜᴡᴒᴟᴒᴠᴡͼ
ӿⱨⱬᴀⱷԐ
ⱫᴀꜚⱩͼᴟᴒꜞꞌԜᴐᴒᴠͼᴀᴀⱪ
ᴀᴒᴐᴡ꞉ꜝꜜͼ⅍᷅᷈ⅎԓͼᴀᴢԝ꞊ᴒᴐᴡͼ
ᴄ꞉ᴡⱳᴑᴟԜᴤԜꞌ
ⱷᴡͼᴤԜᴠͼᴠꜞᴒᴐ꞉ⱱ꞉ᴒᴑͼᴡⱳԜᴡͼᴡⱳᴒͼᴤԜᴠⱳꜝᴢᴡͼԜⱱᴡᴒᴟͼᴡⱳᴒͼꜙᴁ͟ͼᴡⱳᴒᴟԜꜞᴦͼ꞉ᴠͼꜞᴒᴟꜛ꞉ᴡᴡᴒᴑͼԜᴠͼꞌꜝꜜⱲͼԜᴠͼᴡⱳᴒͼ
ⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟͼᴑᴒᴡᴒᴟꜛ꞉ꜜᴒᴑͼᴡⱳԜᴡͼᴑꜝ꞉ꜜⱲͼᴠꜝͼᴤꜝᴢꞌᴑͼꜜꜝᴡͼꜞꞌԜᴐᴒͼᴡⱳᴒͼᴠᴢԝ꞊ᴒᴐᴡͼԜᴡͼԜꜜᴦͼᴢꜜᴑᴢᴒͼ
ᴠԜⱱᴒᴡᴦͼᴟ꞉ᴠꞋͼԜꜜᴑͼᴤꜝᴢꞌᴑͼԝᴒͼԜꜞꜞꞌ꞉ᴐԜԝꞌᴒͼᴡꜝͼᴠᴢԝ꞊ᴒᴐᴡᴠͼᴤⱳꜝͼԜᴟᴒͼԜᴡͼꞌᴒԜᴠᴡͼ᷈˲ͼᴦᴒԜᴟᴠͼꜝⱱͼԜⱲᴒ᷅
ᴀᴒᴐᴡ꞉ꜝꜜͼⅎ᷅᷈ԓͼᴀᴐᴟᴒᴒꜜ꞉ꜜⱲ
ⱴꜝᴢᴟͼԜᴑᴑ꞉ᴡ꞉ꜝꜜԜꞌͼꜞᴟᴒⱲꜜԜꜜᴐᴦͼᴡᴒᴠᴡᴠͼӿᴢᴟ꞉ꜜᴒͼꜝᴟͼᴠᴒᴟᴢꜛԐͼᴤᴒᴟᴒͼᴠᴐⱳᴒᴑᴢꞌᴒᴑͼꜝꜜͼⱫԜᴦᴠ᷉˲ԓͼ᷿⅍ԓͼ
᷈᷉˲ԓͼԜꜜᴑͼ᷿᷈᷾ͼⱱꜝᴟͼꜛꜝꜜ꞉ᴡꜝᴟ꞉ꜜⱲͼꜞᴟᴒⱲꜜԜꜜᴐᴦͼᴑᴢᴟ꞉ꜜⱲͼᴡᴟᴒԜᴡꜛᴒꜜᴡ᷅
ᴀᴡᴢᴑᴦͼⱨᴐᴡ꞉ᴣ꞉ᴡ꞉ᴒᴠͼᴀᴐⱳᴒᴑᴢꞌᴒԓͼ
͟ᴟᴒⱲꜜԜꜜᴐᴦͼᴁᴒᴠᴡͼӿⱱᴒꜛԜꞌᴒᴠԐͼ
ԜꜜᴑͼⱴꜝꜝᴡꜜꜝᴡᴒͼӺⅎⱢͼᴀᴒᴐᴡ꞉ꜝꜜᴠͼ
ⅎ᷅⅍ԓͼⅎ᷅˲ԓͼⅎ᷅᷈᷈ԓͼԜꜜᴑͼⅎ᷅᷈᷾
ᴀꜞᴒᴐ꞉ⱱ꞉ᴒᴑͼᴡⱳᴒͼ꞉ꜜᴠᴡᴟᴢꜛᴒꜜᴡᴠͼӿⱬϷ᷿ⱫͼԜꜜᴑͼⱨⱬ᷄ϷꜝꜙԐͼᴢᴠᴒᴑͼⱱꜝᴟͼꜟᴢԜꞌ꞉ᴡᴦͼꜝⱱͼꞌ꞉ⱱᴒͼ
ԜᴠᴠᴒᴠᴠꜛᴒꜜᴡᴠͼꜝꜜͼⱫԜᴦᴠͼ᷇ԓͼⱠ˲ᶐ᷊ԓͼ᷈˲᷉ᶐ᷊ԓͼԜꜜᴑͼ᷊᷉˲ᶐ᷊᷅
ᴀᴒᴐᴡ꞉ꜝꜜͼⅎ᷊᷅ͼӿᴀᴡԜᴟᴡͼꜝⱱͼ
ᴁᴟᴒԜᴡꜛᴒꜜᴡͼ͟ᴒᴟ꞉ꜝᴑԐⱢͼ
ᴀᴒᴐᴡ꞉ꜝꜜᴠⅎ᷅᷈᷇ͼԜꜜᴑⅎ᷿᷅᷈ͼ
ӿⱪꜝꜜᴡ꞉ꜜᴢԜᴡ꞉ꜝꜜͼꜝⱱͼᴁᴟᴒԜᴡꜛᴒꜜᴡͼ
͟ᴒᴟ꞉ꜝᴑԐⱢͼᴀᴒᴐᴡ꞉ꜝꜜⅎ᷅᷈ⅎͼ
ӿⱴ꞉ꜜԜꞌͼⱴꜝꞌꞌꜝᴤ᷄ᴢꜞͼᴃ꞉ᴠ꞉ᴡԐ
ᴀꜞᴒᴐ꞉ⱱ꞉ᴒᴑͼᴡⱳᴒͼԜᴑᴑ꞉ᴡ꞉ꜝꜜԜꞌͼԜᴠᴠᴒᴠᴠꜛᴒꜜᴡᴠͼⱱꜝᴟͼⱨⱬ᷄ϷꜝꜙͼꜝꜜͼⱫԜᴦᴠͼ᷉˲ᶐ᷊ԓͼ᷿⅍ᶐ᷊ԓͼ᷈᷉⅍ᶐ᷊ԓͼ
Ԝꜜᴑͼ᷿᷈᷾ᶐ᷊ͼⱱꜝᴟͼᴐꞌᴒԜᴟͼᴑᴒꜛԜᴟᴐԜᴡ꞉ꜝꜜ᷅
ᴀᴒᴐᴡ꞉ꜝꜜᴠͼⅎ᷅⅍ԓ ⅎ᷅˲ԓͼⅎ᷅᷈᷈᷅ͼͼ
ⅎ᷅᷈᷾
ⱫᴀꜚⱩͼᴟᴒꜞꞌԜᴐᴒᴠͼᴀᴀⱪ᷅
ᴀᴒᴐᴡ꞉ꜝꜜᴠⅎ᷅Ⱡԓͼⅎ᷅᷈᷇ԓͼⅎ᷅᷈᷈ԓͼ
ⅎ᷅᷈᷉ԓͼⅎ᷅᷈᷾
ᴁᴒᴥᴡͼԜᴑᴑᴒᴑͼᴡꜝͼꜞᴟꜝᴣ꞉ᴑᴒͼԜꜜͼꜝᴣᴒᴟᴣ꞉ᴒᴤͼꜝⱱͼᴡⱳᴒͼⱲᴒꜜᴒᴟԜꞌͼꜞꞌԜꜜͼⱱꜝᴟͼᴡⱳᴒͼᴠᴡԜᴡ꞉ᴠᴡ꞉ᴐԜꞌͼԜꜜԜꞌᴦᴠᴒᴠ᷅ͼ
ᴀᴒᴐᴡ꞉ꜝꜜͼⱠ᷅᷈ԓͼⱵᴒꜜᴒᴟԜꞌͼ
ⱪꜝꜜᴠ꞉ᴑᴒᴟԜᴡ꞉ꜝꜜᴠ
ᴁᴒᴥᴡͼⱱꜝᴟᶰᴠԜꜛꜞꞌᴒͼᴠ꞉ᴧᴒͼᴑᴒᴡᴒᴟꜛ꞉ꜜԜᴡ꞉ꜝꜜᶱͼᴤԜᴠͼᴢꜞᴑԜᴡᴒᴑͼᴡꜝͼԝᴒͼᴐꜝꜜᴠ꞉ᴠᴡᴒꜜᴡͼᴤ꞉ᴡⱳͼᴡⱳᴒͼ
ᴢꜞᴑԜᴡᴒᴑͼᴠᴡԜᴡ꞉ᴠᴡ꞉ᴐԜꞌͼꜛᴒᴡⱳꜝᴑᴠ᷅
ᴀᴡᴢᴑᴦͼᴀᴦꜜꜝꜞᴠ꞉ᴠⱢͼᴀᴒᴐᴡ꞉ꜝꜜͼ
Ⱡ᷅᷉ԓͼᴀԜꜛꜞꞌᴒͼᴀ꞉ᴧᴒͼ
Ⱬᴒᴡᴒᴟꜛ꞉ꜜԜᴡ꞉ꜝꜜͼ
ⱨᴑᴑᴒᴑͼᴐꜝꜜᴠꜝꞌ꞉ᴑԜᴡᴒᴑͼ꞉ꜜⱱꜝᴟꜛԜᴡ꞉ꜝꜜͼᴟᴒⱲԜᴟᴑ꞉ꜜⱲͼᴟԜꜜᴑꜝꜛ꞉ᴧԜᴡ꞉ꜝꜜͼԜꜜᴑͼᴠᴡᴟԜᴡ꞉ⱱ꞉ᴐԜᴡ꞉ꜝꜜͼ꞉ꜜͼᴡⱳᴒͼ
ᴀᴡԜᴡ꞉ᴠᴡ꞉ᴐԜꞌͼⱨꜜԜꞌᴦᴠ꞉ᴠͼᴠᴒᴐᴡ꞉ꜝꜜͼꜝⱱͼᴡⱳᴒͼꜞᴟꜝᴡꜝᴐꜝꞌ᷅
ᴀᴒᴐᴡ꞉ꜝꜜͼⱠ᷊᷅ԓͼꜚᴒᴡⱳꜝᴑͼꜝⱱͼ
ⱨᴠᴠ꞉Ⱳꜜ꞉ꜜⱲͼᴀᴡᴢᴑᴦͼᴀᴢԝ꞊ᴒᴐᴡᴠͼ
ᴡꜝͼᴁᴟᴒԜᴡꜛᴒꜜᴡͼⱵᴟꜝᴢꜞᴠ
ᴁᴒᴥᴡͼԜᴑᴑᴒᴑͼᴡꜝͼᴐꞌԜᴟ꞉ⱱᴦͼᴡⱳԜᴡͼᴡⱳᴒͼᴠᴢԝ꞊ᴒᴐᴡᴠͼᴤ꞉ꞌꞌͼԝᴒͼԜꜜԜꞌᴦᴧᴒᴑͼԜᴐᴐꜝᴟᴑ꞉ꜜⱲͼᴡꜝͼᴡⱳᴒ꞉ᴟͼ
ᴟԜꜜᴑꜝꜛ꞉ᴧᴒᴑͼᴡᴟᴒԜᴡꜛᴒꜜᴡͼԜᴠᴠ꞉Ⱳꜜꜛᴒꜜᴡ᷅
ᴀᴒᴐᴡ꞉ꜝꜜͼⱠ᷅᷾ԓͼⱨꜜԜꞌᴦᴠ꞉ᴠͼ
͟ꜝꜞᴢꞌԜᴡ꞉ꜝꜜ
ⱨᴑᴑᴒᴑͼᴡⱳᴒͼꜞꜝꜞᴢꞌԜᴡ꞉ꜝꜜᴠͼⱱꜝᴟͼᴐꞌԜᴟ꞉ᴡᴦ᷅
ᴀᴒᴐᴡ꞉ꜝꜜͼⱠ᷿᷅ԓͼⱨꜜԜꞌᴦᴠ꞉ᴠͼꜝⱱͼ
Ⱬ꞉ᴠꜞꜝᴠ꞉ᴡ꞉ꜝꜜ
ⱪꞌԜᴟ꞉ⱱ꞉ᴒᴠͼᴡⱳᴒͼԜꜜԜꞌᴦᴠ꞉ᴠͼꜞꜝꜞᴢꞌԜᴡ꞉ꜝꜜ᷅
ᴀᴒᴐᴡ꞉ꜝꜜͼⱠ᷅⅍ԓͼⱫᴒꜛꜝⱲᴟԜꜞⱳ꞉ᴐᴠͼ
ԜꜜᴑͼⱩԜᴠᴒꞌ꞉ꜜᴒͼ
ⱪⱳԜᴟԜᴐᴡᴒᴟ꞉ᴠᴡ꞉ᴐᴠͼⱨꜜԜꞌᴦᴠᴒᴠ
ⱨᴑᴑᴒᴑͼᴡⱳᴒͼꜛᴒᴡⱳꜝᴑͼꜝⱱͼᴑᴒᴠᴐᴟ꞉ԝ꞉ꜜⱲͼᴡᴟᴒԜᴡꜛᴒꜜᴡͼᴐꜝꜛꜞꞌ꞉ԜꜜᴐᴒͼԜꜜᴑͼᴒᴥᴡᴒꜜᴡͼꜝⱱͼᴒᴥꜞꜝᴠᴢᴟᴒ᷅ͼ
ᴀᴒᴐᴡ꞉ꜝꜜͼⱠ᷅ⅎԓͼᴁᴟᴒԜᴡꜛᴒꜜᴡͼ
ⱪꜝꜛꜞꞌ꞉ԜꜜᴐᴒͼԜꜜᴑͼⱬᴥᴡᴒꜜᴡͼꜝⱱͼ
ⱬᴥꜞꜝᴠᴢᴟᴒ
ⱬⱱⱱ꞉ᴐԜᴐᴦͼᴒꜜᴑꜞꜝ꞉ꜜᴡͼꜞᴒᴟ꞉ꜝᴑͼԝᴒⱲ꞉ꜜꜜ꞉ꜜⱲͼꜝꜜͼⱫԜᴦͼ᷇ͼ꞉ꜜᴠᴡᴒԜᴑͼꜝⱱͼⱫԜᴦͼ᷈᷾᷅ͼ
ϸᴒᴠᴢꞌᴡᴠͼⱱᴟꜝꜛͼᴡⱳᴒͼᴠᴡԜᴡ꞉ᴠᴡ꞉ᴐԜꞌͼꜛꜝᴑᴒꞌͼᴤ꞉ꞌꞌͼԝᴒͼᴟᴒꜞꜝᴟᴡᴒᴑͼ꞉ꜜͼԝꜝᴡⱳͼᴤᴒᴒꞋᴠͼԜꜜᴑͼꜛꜝꜜᴡⱳᴠͼᴡꜝͼ
ᴀᴒᴐᴡ꞉ꜝꜜͼⱠ᷅˲ԓ ⱨꜜԜꞌᴦᴠ꞉ᴠͼꜝⱱͼ
͟ᴟ꞉ꜛԜᴟᴦͼԜꜜᴑͼᴀᴒᴐꜝꜜᴑԜᴟᴦͼ
ⱬⱱⱱ꞉ᴐԜᴐᴦͼⱬꜜᴑꜞꜝ꞉ꜜᴡᴠ

Ⱬᴅ᷄᷉Ⱡ᷊᷇
ⱪꞌ꞉ꜜ꞉ᴐԜꞌͼᴁᴟ꞉Ԝꞌͼ͟ᴟꜝᴡꜝᴐꜝꞌⱡͼⱫᴅ᷄᷉Ⱡ᷊᷊᷇᷄᷇
ⱨꜛᴒꜜᴑꜛᴒꜜᴡͼ᷊᷅᷇ͼⱴ꞉ꜜԜꞌⱡͼ᷇ⱠͼꜗԜꜜᴢԜᴟᴦͼ᷉᷇᷈ⅎ
ⱪꜝꜜⱱ꞉ᴑᴒꜜᴡ꞉Ԝꞌ
͟ԜⱲᴒͼ᷈᷇᷇
ⱫᴦԜᴥͼⱪꜝᴟꜞ᷅
Protocol Amendments
Summary of Change(s) Since Last Version of Approved Protocol
Amendment Number
2.0
Amendment Date
21 April 2016
Global/Country/Site 
Specific
Global
Description of Change
Section(s) Affected by 
Change
ⱱԜᴐ꞉ꞌ꞉ᴡԜᴡᴒͼᴐꞌ꞉ꜜ꞉ᴐԜꞌͼ꞉ꜜᴡᴒᴟꜞᴟᴒᴡԜᴡ꞉ꜝꜜ᷅
ᴀᴡԜᴡ꞉ᴠᴡ꞉ᴐԜꞌͼꜛᴒᴡⱳꜝᴑᴠͼᴤᴒᴟᴒͼᴢꜞᴑԜᴡᴒᴑͼᴡꜝͼᴢᴠᴒͼԜͼⱲᴒꜜᴒᴟԜꞌ꞉ᴧᴒᴑͼꞌ꞉ꜜᴒԜᴟͼꜛꜝᴑᴒꞌͼᴟԜᴡⱳᴒᴟͼᴡⱳԜꜜͼ
ⱲᴒꜜᴒᴟԜꞌ꞉ᴧᴒᴑͼᴒᴠᴡ꞉ꜛԜᴡ꞉ꜜⱲͼᴒꜟᴢԜᴡ꞉ꜝꜜͼꜛꜝᴑᴒꞌͼⱱꜝᴟͼᴡⱳᴒͼꜞᴟ꞉ꜛԜᴟᴦͼԜꜜԜꞌᴦᴠ꞉ᴠ᷅ͼᴁⱳ꞉ᴠͼᴢꜞᴑԜᴡᴒᴑͼ
ԜꜜԜꞌᴦᴠ꞉ᴠͼԜꜞꜞᴟꜝԜᴐⱳͼԜꞌᴠꜝͼԜꜞꜞꞌ꞉ᴒᴠͼᴡꜝͼᴡⱳᴒͼᴠᴒᴐꜝꜜᴑԜᴟᴦͼᴒꜜᴑꜞꜝ꞉ꜜᴡᴠ᷅
ⱬᴥꜞꞌԜ꞉ꜜᴠͼᴒꜜᴑꜞꜝ꞉ꜜᴡͼԜꜜԜꞌᴦᴠᴒᴠͼԝԜᴠᴒᴑͼꜝꜜͼⱲᴒꜜᴒᴟԜꞌ꞉ᴧᴒᴑͼꞌ꞉ꜜᴒԜᴟͼꜛꜝᴑᴒꞌ᷅
ᴁⱳᴒͼᴠᴒᴐꜝꜜᴑԜᴟᴦͼᴒꜜᴑꜞꜝ꞉ꜜᴡͼᶰᴁ꞉ꜛᴒͼᴡꜝͼⱱ꞉ᴟᴠᴡͼԜᴡᴡԜᴐꞋԓͼ꞉ᴒԓͼᴑᴢᴟԜᴡ꞉ꜝꜜͼᴡⱳԜᴡͼԜͼᴠᴢԝ꞊ᴒᴐᴡͼ꞉ᴠͼԜᴡᴡԜᴐꞋͼ
ⱱᴟᴒᴒͼᴢꜜᴡ꞉ꞌͼᴡⱳᴒ꞉ᴟͼⱱ꞉ᴟᴠᴡͼԜᴡᴡԜᴐꞋᶱͼᴤԜᴠͼᴟᴒꜛꜝᴣᴒᴑͼⱱᴟꜝꜛͼᴡⱳᴒͼᴟԜꜜꞋͼꜝᴟᴑᴒᴟͼԜꜜᴑͼᴤ꞉ꞌꞌͼԝᴒͼ
ᴐꜝꜜᴠ꞉ᴑᴒᴟᴒᴑͼԜꜜͼᴒᴥꜞꞌꜝᴟԜᴡꜝᴟᴦͼᴒꜜᴑꜞꜝ꞉ꜜᴡ᷅ͼⱷᴡͼᴤԜᴠͼꜛꜝᴑ꞉ⱱ꞉ᴒᴑͼᴡꜝͼᶰᴁ꞉ꜛᴒͼᴡꜝͼⱱ꞉ᴟᴠᴡͼⱶⱨⱬͼԜᴡᴡԜᴐꞋͼ
ԜⱱᴡᴒᴟͼⱫԜᴦͼ᷈᷾ԓͼ꞉᷅ᴒ᷅ԓͼᴑᴢᴟԜᴡ꞉ꜝꜜͼᴡⱳԜᴡͼԜͼᴠᴢԝ꞊ᴒᴐᴡͼ꞉ᴠͼԜᴡᴡԜᴐꞋ᷄ⱱᴟᴒᴒͼԜⱱᴡᴒᴟͼⱫԜᴦͼ᷈᷾ᶱͼᴡꜝͼԜꞌꞌꜝᴤͼ
ᴒꜜꜝᴢⱲⱳͼᴡ꞉ꜛᴒͼᴡꜝͼⱱ꞉ᴟᴠᴡͼԜᴡᴡԜᴐꞋͼⱱꜝᴟͼᴡⱳ꞉ᴠͼᴒꜜᴑꜞꜝ꞉ꜜᴡͼԜᴠᴠᴒᴠᴠꜛᴒꜜᴡ᷅
ᴁⱳᴒͼᴠᴒᴐꜝꜜᴑԜᴟᴦͼᴒꜜᴑꜞꜝ꞉ꜜᴡͼᶰ꜠ᴢꜛԝᴒᴟͼꜝⱱͼⱳ꞉Ⱳⱳ᷄ꜛꜝᴟԝ꞉ᴑ꞉ᴡᴦͼⱶⱨⱬͼԜᴡᴡԜᴐꞋᴠᶱͼᴟᴒꜛꜝᴣᴒᴑͼⱱᴟꜝꜛ
ᴡⱳᴒͼᴟԜꜜꞋͼꜝᴟᴑᴒᴟͼԜꜜᴑͼᴤ꞉ꞌꞌͼԝᴒͼᴐꜝꜜᴠ꞉ᴑᴒᴟᴒᴑͼԜꜜͼᴒᴥꜞꞌꜝᴟԜᴡꜝᴟᴦͼᴒꜜᴑꜞꜝ꞉ꜜᴡ᷅
ᴀᴒᴐᴡ꞉ꜝꜜͼⱠ᷅˲ԓͼᴀᴒᴐꜝꜜᴑԜᴟᴦͼ
ⱬⱱⱱ꞉ᴐԜᴐᴦͼⱬꜜᴑꜞꜝ꞉ꜜᴡᴠ
ⱨᴑᴑᴒᴑͼԜᴑᴑ꞉ᴡ꞉ꜝꜜԜꞌͼᴑᴒᴡԜ꞉ꞌᴠͼⱱꜝᴟͼᴡⱳᴒͼᴠᴡԜᴡ꞉ᴠᴡ꞉ᴐԜꞌͼԜꜜԜꞌᴦᴠ꞉ᴠⱢͼᴐꞌԜᴟ꞉ⱱ꞉ᴒᴑͼꜜꜝͼꜞꞌԜꜜͼⱱꜝᴟͼ꞉ꜜᴡᴒᴟ꞉ꜛͼ
ԜꜜԜꞌᴦᴠ꞉ᴠͼԜꜜᴑͼꜞꞌԜꜜᴠͼⱱꜝᴟͼⱫᴀꜚⱩ᷅ͼ
ⱷꜜͼⱲᴒꜜᴒᴟԜꞌԓͼᴡⱳᴒͼᴠᴡԜᴡ꞉ᴠᴡ꞉ᴐԜꞌͼꜛᴒᴡⱳꜝᴑᴠͼᴤᴒᴟᴒͼᴑᴒᴠᴐᴟ꞉ԝᴒᴑͼᴤ꞉ᴡⱳͼԜᴑᴑ꞉ᴡ꞉ꜝꜜԜꞌͼ꞉ꜜⱱꜝᴟꜛԜᴡ꞉ꜝꜜͼ
ᴟᴒⱲԜᴟᴑ꞉ꜜⱲͼᴡⱳᴒͼⱲᴒꜜᴒᴟԜꞌͼᴠᴡԜᴡ꞉ᴠᴡ꞉ᴐԜꞌͼᴐꜝꜜᴠ꞉ᴑᴒᴟԜᴡ꞉ꜝꜜᴠͼԜꜜᴑͼᴠᴡԜᴡ꞉ᴠᴡ꞉ᴐԜꞌ᷆ԜꜜԜꞌᴦᴡ꞉ᴐԜꞌͼ꞉ᴠᴠᴢᴒᴠͼӿᴒⱲԓͼ
Ԝᴑ꞊ᴢᴠᴡꜛᴒꜜᴡͼⱱꜝᴟͼᴐꜝᴣԜᴟ꞉ԜᴡᴒᴠԓͼⱳԜꜜᴑꞌ꞉ꜜⱲͼꜝⱱͼᴑᴟꜝꜞꜝᴢᴡᴠͼԜꜜᴑͼᴑԜᴡԜͼꜛꜝꜜ꞉ᴡꜝᴟ꞉ꜜⱲԓͼⱳԜꜜᴑꞌ꞉ꜜⱲͼꜝⱱͼ
ᴑᴟꜝꜞꜝᴢᴡᴠͼꜝᴟͼꜛ꞉ᴠᴠ꞉ꜜⱲͼᴑԜᴡԜԓͼ꞉ꜜᴡᴒᴟ꞉ꜛͼԜꜜԜꞌᴦᴠ꞉ᴠԜꜜᴑͼᴑԜᴡԜͼꜛꜝꜜ꞉ᴡꜝᴟ꞉ꜜⱲԓͼꜛᴢꞌᴡ꞉ᴐᴒꜜᴡᴒᴟͼ
ᴠᴡᴢᴑ꞉ᴒᴠԓͼԜꜜᴑͼᴠᴒꜜᴠ꞉ᴡ꞉ᴣ꞉ᴡᴦͼԜꜜԜꞌᴦᴠᴒᴠԐ᷅
ᴀᴒᴐᴡ꞉ꜝꜜͼⱠ᷅᷈᷉ԓͼ
ᴀᴡԜᴡ꞉ᴠᴡ꞉ᴐԜꞌ᷆ⱨꜜԜꞌᴦᴡ꞉ᴐͼⱷᴠᴠᴢᴒᴠ
ꜚᴢꞌᴡ꞉ꜞꞌ꞉ᴐ꞉ᴡᴦͼꜞᴟꜝᴐᴒᴑᴢᴟᴒᴠͼᴤᴒᴟᴒͼᴠꜞᴒᴐ꞉ⱱ꞉ᴒᴑͼ꞉ꜜͼⱲᴟᴒԜᴡᴒᴟͼᴑᴒᴡԜ꞉ꞌ᷅ͼᴀꜞᴒᴐ꞉ⱱ꞉ᴐԜꞌꞌᴦԓͼԜͼⱲᴒꜜᴒᴟԜꞌͼ
ⱲԜᴡᴒꞋᴒᴒꜞ꞉ꜜⱲͼꜞᴟꜝᴐᴒᴑᴢᴟᴒͼᴤ꞉ꞌꞌͼԝᴒͼᴢᴠᴒᴑͼᴡꜝͼᴠᴡᴟꜝꜜⱲꞌᴦͼᴐꜝꜜᴡᴟꜝꞌͼᴡⱳᴒͼⱲꞌꜝԝԜꞌͼⱴᴄⱬϸͼ꞉ꜜͼᴡⱳᴒͼ
ⱳ꞉ᴒᴟԜᴟᴐⱳ꞉ᴐԜꞌͼᴡᴒᴠᴡ꞉ꜜⱲͼꜝⱱͼᴡⱳᴒͼꜞᴟ꞉ꜛԜᴟᴦͼԜꜜᴑͼᴠᴒᴐꜝꜜᴑԜᴟᴦͼᴒꜜᴑꜞꜝ꞉ꜜᴡᴠͼᴐꜝꜜᴑᴢᴐᴡᴒᴑͼԜᴡͼᴡⱳᴒͼ
᷈᷅⅍ⅎӼͼᴠ꞉Ⱳꜜ꞉ⱱ꞉ᴐԜꜜᴐᴒͼꞌᴒᴣᴒꞌͼⱱꜝᴟͼᴒԜᴐⱳͼԜᴐᴡ꞉ᴣᴒͼᴡᴟᴒԜᴡꜛᴒꜜᴡͼⱲᴟꜝᴢꜞͼᴐꜝꜛꜞԜᴟᴒᴑͼᴤ꞉ᴡⱳͼᴡⱳᴒͼ
ꜞꞌԜᴐᴒԝꜝͼⱲᴟꜝᴢꜞ᷅
ᴀᴒᴐᴡ꞉ꜝꜜͼⱠ᷅᷈᷉ԓͼ
ᴀᴡԜᴡ꞉ᴠᴡ꞉ᴐԜꞌ᷆ⱨꜜԜꞌᴦᴡ꞉ᴐͼⱷᴠᴠᴢᴒᴠ
ⱨᴑᴑᴒᴑͼᴡꜝͼԝᴟ꞉ᴒⱱꞌᴦͼ꞉ꜜᴡᴟꜝᴑᴢᴐᴒͼᴡⱳᴒͼꜞꞌԜꜜͼⱱꜝᴟͼᴠᴒꜜᴠ꞉ᴡ꞉ᴣ꞉ᴡᴦͼԜꜜԜꞌᴦᴠ꞉ᴠԓͼᴤⱳ꞉ᴐⱳͼᴤ꞉ꞌꞌͼԝᴒͼ
ᴑᴒᴠᴐᴟ꞉ԝᴒᴑͼ꞉ꜜͼᴡⱳᴒͼᴠᴡԜᴡ꞉ᴠᴡ꞉ᴐԜꞌͼԜꜜԜꞌᴦᴠ꞉ᴠͼꜞꞌԜꜜ᷅
ᴀᴒᴐᴡ꞉ꜝꜜͼⱠ᷅᷈᷉᷅⅍ԓͼᴀᴡԜᴡ꞉ᴠᴡ꞉ᴐԜꞌ
ⱨꜜԜꞌᴦᴠᴒᴠ
ᴀᴡᴢᴑᴦͼᴐꜝꜜᴡԜᴐᴡͼԜꜜᴑͼꜚᴒᴑ꞉ᴐԜꞌͼⱫ꞉ᴟᴒᴐᴡꜝᴟͼᴢꜞᴑԜᴡᴒᴑͼ꞉ꜜͼᴁԜԝꞌᴒͼ᷉᷅ͼ
ᴀᴒᴐᴡ꞉ꜝꜜͼ᷈᷇ԓͼᴀᴡᴢᴑᴦ
ⱨᴑꜛ꞉ꜜ꞉ᴠᴡᴟԜᴡ꞉ᴣᴒͼᴀᴡᴟᴢᴐᴡᴢᴟᴒ
ⱪꞌԜᴟ꞉ⱱ꞉ᴒᴠͼⱫᴀꜚⱩͼꜞᴟꜝᴐᴒᴑᴢᴟᴒᴠ᷅
ᴀᴒᴐᴡ꞉ꜝꜜͼ᷈᷇᷅ⅎԓͼⱫԜᴡԜͼᴀԜⱱᴒᴡᴦ
ꜚꜝꜜ꞉ᴡꜝᴟ꞉ꜜⱲ
꜠ᴒᴤͼᴡᴒᴥᴡ
꜠ᴒᴤͼᴀᴒᴐᴡ꞉ꜝꜜⱡͼᴀᴒᴐᴡ꞉ꜝꜜͼ᷈᷇᷅Ⱡԓ
͟ᴟᴒꜛԜᴡᴢᴟᴒͼⱪꞌꜝᴠᴢᴟᴒͼꜝⱱͼᴡⱳᴒ
ᴀᴡᴢᴑᴦ
ⱪꞌԜᴟ꞉ⱱ꞉ᴒᴠͼᴑԜᴡԜͼⱳԜꜜᴑꞌ꞉ꜜⱲͼᴐꜝꜜᴠ꞉ᴑᴒᴟԜᴡ꞉ꜝꜜᴠᴡꜝͼꜞᴟᴒᴣᴒꜜᴡͼꜞꜝᴡᴒꜜᴡ꞉Ԝꞌͼᴢꜜԝꞌ꞉ꜜᴑ꞉ꜜⱲ᷅
꜠ᴒᴤͼᴀᴒᴐᴡ꞉ꜝꜜⱡͼᴀᴒᴐᴡ꞉ꜝꜜ
᷈᷇᷅᷈᷉ԓͼⱫԜᴡԜͼⱶԜꜜᴑꞌ꞉ꜜⱲ
ⱪꜝꜜᴠ꞉ᴑᴒᴟԜᴡ꞉ꜝꜜᴠ

Ⱬᴅ᷄᷉Ⱡ᷊᷇
ⱪꞌ꞉ꜜ꞉ᴐԜꞌͼᴁᴟ꞉Ԝꞌͼ͟ᴟꜝᴡꜝᴐꜝꞌⱡͼⱫᴅ᷄᷉Ⱡ᷊᷊᷇᷄᷇
ⱨꜛᴒꜜᴑꜛᴒꜜᴡͼ᷊᷅᷇ͼⱴ꞉ꜜԜꞌⱡͼ᷇ⱠͼꜗԜꜜᴢԜᴟᴦͼ᷉᷇᷈ⅎ
ⱪꜝꜜⱱ꞉ᴑᴒꜜᴡ꞉Ԝꞌ
͟ԜⱲᴒͼ᷈᷇᷈
ⱫᴦԜᴥͼⱪꜝᴟꜞ᷅
Protocol Amendments
Summary of Change(s) Since Last Version of Approved Protocol
Amendment Number
2.0
Amendment Date
21 April 2016
Global/Country/Site 
Specific
Global
Description of Change
Section(s) Affected by 
Change
ⱨᴑᴑᴒᴑͼᴡᴒᴥᴡᴡꜝͼԝᴒͼᴐꜝꜜᴠ꞉ᴠᴡᴒꜜᴡͼᴤ꞉ᴡⱳͼ᷉᷈ͼⱪⱴϸͼ᷿᷾ͼ᷉ӿԝԐͼӿ᷈ⱠⱠ˲Ԑ᷅ͼ
꜠ᴒᴤͼᴀᴒᴐᴡ꞉ꜝꜜⱡͼᴀᴒᴐᴡ꞉ꜝꜜ
᷈᷇᷅᷈᷾ԓͼⱴ꞉ꜜԜꜜᴐ꞉Ԝꞌ
Ⱬ꞉ᴠᴐꞌꜝᴠᴢᴟᴒ
ⱨᴑᴑᴒᴑͼᴡᴒᴥᴡͼᴡꜝͼԜꞌ꞉Ⱳꜜͼᴤ꞉ᴡⱳͼꜞꜝᴡᴒꜜᴡ꞉Ԝꞌͼᴑ꞉ᴠᴐꞌꜝᴠᴢᴟᴒͼꜝⱱͼᴠᴡᴢᴑᴦͼᴟᴒᴠᴢꞌᴡᴠ᷅
ᴀᴒᴐᴡ꞉ꜝꜜͼ᷿᷈᷇᷅᷈ԓͼ͟ᴢԝꞌ꞉ᴐԜᴡ꞉ꜝꜜ
ԜꜜᴑͼⱫ꞉ᴠᴐꞌꜝᴠᴢᴟᴒͼ͟ꜝꞌ꞉ᴐᴦ
ᴁⱳᴒͼ͟ᴟꜝᴡꜝᴐꜝꞌͼⱨꜛᴒꜜᴑꜛᴒꜜᴡͼ᷈᷅᷇ͼ꞉ꜜᴐꞌᴢᴑᴒᴠͼᴐⱳԜꜜⱲᴒᴠᴡꜝͼᴡⱳᴒͼꜝᴟ꞉Ⱳ꞉ꜜԜꞌͼꜞᴟꜝᴡꜝᴐꜝꞌԓͼᴠᴢꜛꜛԜᴟ꞉ᴧᴒᴑͼԜᴠͼ
ⱱꜝꞌꞌꜝᴤᴠⱡ

ᴁⱳᴒͼꞌ꞉ᴠᴡͼꜝⱱͼ꞉ꜜԜᴐᴡ꞉ᴣᴒͼ꞉ꜜⱲᴟᴒᴑ꞉ᴒꜜᴡᴠͼԜꜜᴑͼᴑᴒᴠᴐᴟ꞉ꜞᴡ꞉ꜝꜜͼꜝⱱͼᴡᴟᴒԜᴡꜛᴒꜜᴡᴠͼ꞉ꜜͼᴡⱳᴒͼᴠᴦꜜꜝꜞᴠ꞉ᴠͼԜꜜᴑͼ꞉ꜜͼ
ᴀᴒᴐᴡ꞉ꜝꜜͼ᷿᷅᷈ͼ꞉ᴠͼᴢꜞᴑԜᴡᴒᴑͼᴡꜝͼᴟᴒⱱꞌᴒᴐᴡͼᴡⱳᴒͼᴢᴠᴒͼꜝⱱͼ᷿᷈᷇ͼꜛⱲ᷆ꜛꜙͼᴐꜝꜜᴐᴒꜜᴡᴟԜᴡ꞉ꜝꜜͼⱫᴅ᷄᷉Ⱡ᷊᷇ͼ
꞉ꜜᴠᴡᴒԜᴑͼꜝⱱͼ᷈᷇᷇ͼꜛⱲ᷆ꜛꜙͼᴐꜝꜜᴐᴒꜜᴡᴟԜᴡ꞉ꜝꜜͼⱫᴅ᷄᷉Ⱡ᷊᷇᷅ꜚ꞉ꜜꜝᴟͼᴢꜞᴑԜᴡᴒᴠͼԜᴟᴒͼꜛԜᴑᴒͼᴡꜝͼᴡⱳᴒͼ
ᴐꜝꜛꜞꜝꜜᴒꜜᴡᴠͼꜝⱱͼԝꜝᴡⱳͼⱫᴅ᷄᷉Ⱡ᷊᷇ͼԜꜜᴑͼ͟ꞌԜᴐᴒԝꜝ᷅ͼᴁⱳᴒͼꜜᴢꜛԝᴒᴟͼꜝⱱͼ꞉ꜜ꞊ᴒᴐᴡ꞉ꜝꜜᴠͼԜꜜᴑͼᴡⱳᴒͼᴣꜝꞌᴢꜛᴒͼ
ꜝⱱͼᴒԜᴐⱳͼ꞉ꜜ꞊ᴒᴐᴡ꞉ꜝꜜͼꜝⱱͼⱫᴅ᷄᷉Ⱡ᷊᷇ͼԜꜜᴑͼ͟ꞌԜᴐᴒԝꜝͼԜᴟᴒͼᴢꜞᴑԜᴡᴒᴑͼᴡꜝͼᴟᴒⱱꞌᴒᴐᴡͼᴡⱳᴒͼᴐⱳԜꜜⱲᴒͼ꞉ꜜͼ
ᴐꜝꜜᴐᴒꜜᴡᴟԜᴡ꞉ꜝꜜ᷅

ᴁⱳᴒͼ᷈ͼꜛꜝꜜᴡⱳͼꜜꜝꜜ᷄ⱳᴢꜛԜꜜͼꜞᴟ꞉ꜛԜᴡᴒͼᴑԜᴡԜͼ꞉ꜜͼᴡⱳᴒͼᴀԜⱱᴒᴡᴦͼϸԜᴡ꞉ꜝꜜԜꞌᴒͼⱱꜝᴟͼⱫᴅ᷄᷉Ⱡ᷊᷇ͼⱳԜᴠͼԝᴒᴒꜜͼ
ᴟᴒꜞꞌԜᴐᴒᴑͼᴤ꞉ᴡⱳͼ⅍ͼꜛꜝꜜᴡⱳͼꜜꜝꜜ᷄ⱳᴢꜛԜꜜͼꜞᴟ꞉ꜛԜᴡᴒͼᴑԜᴡԜͼԜᴠͼᴡⱳᴒͼ⅍ͼꜛꜝꜜᴡⱳͼᴑԜᴡԜͼ꞉ᴠͼԜᴣԜ꞉ꞌԜԝꞌᴒͼԜꜜᴑͼ
ꜛꜝᴟᴒͼᴟᴒꞌᴒᴣԜꜜᴡͼⱱꜝᴟͼᴡⱳ꞉ᴠͼꞌꜝꜜⱲ᷄ᴡᴒᴟꜛͼꜞᴟꜝꜞⱳᴦꞌԜᴥ꞉ᴠͼᴡᴟ꞉Ԝꞌ᷅ͼᴁⱳᴒͼᴑᴒᴠᴐᴟ꞉ꜞᴡ꞉ꜝꜜͼꜝⱱͼᴡⱳᴒͼᴟᴢꜜ᷄꞉ꜜͼꜞᴒᴟ꞉ꜝᴑͼ
꞉ᴠͼᴢꜞᴑԜᴡᴒᴑͼᴡꜝͼᴐꞌԜᴟ꞉ⱱᴦͼᴡⱳԜᴡͼ꞉ⱱͼԜͼᴠᴢԝ꞊ᴒᴐᴡᶳᴠͼᴟᴢꜜ᷄꞉ꜜͼꜞᴒᴟ꞉ꜝᴑͼᴒᴥᴡᴒꜜᴑᴒᴑͼᴡꜝͼ˲ͼᴤᴒᴒꞋᴠͼᴡⱳᴒꜜͼ꞉ꜜͼꜝᴟᴑᴒᴟͼ
ᴡꜝͼԝᴒͼᴒꞌ꞉Ⱳ꞉ԝꞌᴒͼⱱꜝᴟͼᴒꜜᴟꜝꞌꞌꜛᴒꜜᴡͼᴡⱳᴒᴦͼꜛᴢᴠᴡͼᴐꜝꜛꜞꞌᴒᴡᴒͼᴡⱳᴒͼⱱᴢꞌꞌͼ˲ͼᴤᴒᴒꞋᴠͼꜞᴟ꞉ꜝᴟͼᴡꜝͼᴒꜜᴡᴒᴟ꞉ꜜⱲͼᴡⱳᴒͼ
ᴡᴟᴒԜᴡꜛᴒꜜᴡͼꜞᴒᴟ꞉ꜝᴑ
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ⱷꜜᴑ꞉ᴣ꞉ᴑᴢԜꞌͼᴠᴡᴢᴑᴦͼꜞԜᴟᴡ꞉ᴐ꞉ꜞԜꜜᴡͼᴠᴡꜝꜞꜞ꞉ꜜⱲͼᴟᴢꞌᴒᴠͼԜᴟᴒͼᴢꜞᴑԜᴡᴒᴑͼᴡꜝͼᴐꞌԜᴟ꞉ⱱᴦͼᴡⱳԜᴡͼᴡⱳᴒͼⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟͼ
ⱳԜᴠͼᴠꜝꞌᴒͼᴑ꞉ᴠᴐᴟᴒᴡ꞉ꜝꜜͼᴡꜝͼᴑ꞉ᴠᴐꜝꜜᴡ꞉ꜜᴢᴒͼᴠᴢԝ꞊ᴒᴐᴡͼᴑꜝᴠ꞉ꜜⱲͼԜꜜᴑͼᴡⱳԜᴡͼᴡⱳᴒͼꜚᴒᴑ꞉ᴐԜꞌͼꜚꜝꜜ꞉ᴡꜝᴟͼ꞉ᴠͼ
ԜᴣԜ꞉ꞌԜԝꞌᴒͼⱱꜝᴟͼᴐꜝꜜᴠᴢꞌᴡԜᴡ꞉ꜝꜜ᷅

ᴁⱳᴒͼᴒᴥꜞᴒᴐᴡᴒᴑͼꜜᴢꜛԝᴒᴟͼꜝⱱͼᴠᴢԝ꞊ᴒᴐᴡᴠͼԜⱲᴒͼ᷈᷉ͼᴡꜝͼ᷈ⅎͼᴡꜝͼԝᴒͼᴒꜜᴟꜝꞌꞌᴒᴑͼ꞉ꜜͼᴡⱳᴒͼᴠᴡᴢᴑᴦͼ꞉ᴠͼԜᴑᴑᴒᴑ᷅

ᴁⱳᴒͼԝꞌ꞉ꜜᴑ꞉ꜜⱲͼԜꜜᴑͼᴢꜜԝꞌ꞉ꜜᴑ꞉ꜜⱲͼᴡᴒᴥᴡͼ꞉ᴠͼᴢꜞᴑԜᴡᴒᴑͼᴡꜝͼᴐꞌԜᴟ꞉ⱱᴦͼᴡⱳԜᴡͼᴡⱳᴒͼⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟͼⱳԜᴠͼᴠꜝꞌᴒͼ
ᴑ꞉ᴠᴐᴟᴒᴡ꞉ꜝꜜͼᴡꜝͼԝᴟᴒԜꞋͼᴡⱳᴒͼᴡᴟᴒԜᴡꜛᴒꜜᴡͼᴐꜝᴑᴒͼ꞉ꜜͼԜꜜͼᴒꜛᴒᴟⱲᴒꜜᴐᴦͼᴠ꞉ᴡᴢԜᴡ꞉ꜝꜜͼᴡⱳᴟꜝᴢⱲⱳͼ꞉ꜛꜛᴒᴑ꞉Ԝᴡᴒͼ
Ԝꜜᴑͼᴢꜜᴟᴒᴠᴡᴟ꞉ᴐᴡᴒᴑͼԜᴐᴐᴒᴠᴠͼᴡꜝͼᴡⱳᴒͼⱷᴄϸᴀͼᴠᴦᴠᴡᴒꜛ᷅ͼᴁⱳᴒͼᴡᴒᴥᴡͼ꞉ᴠͼⱱᴢᴟᴡⱳᴒᴟͼᴢꜞᴑԜᴡᴒᴑͼᴡꜝͼᴐꞌԜᴟ꞉ⱱᴦͼᴡⱳԜᴡͼ
ᴡⱳᴒͼⱫᴦԜᴥͼ͟ⱳԜᴟꜛԜᴐꜝᴣ꞉Ⱳ꞉ꞌԜꜜᴐᴒͼӿ͟ᴃԐͼⱫᴒꜞԜᴟᴡꜛᴒꜜᴡͼᴤ꞉ꞌꞌͼԝᴒͼꜞᴟꜝᴣ꞉ᴑᴒᴑͼᴤ꞉ᴡⱳͼᴡᴟᴒԜᴡꜛᴒꜜᴡͼ
Ԝᴠᴠ꞉Ⱳꜜꜛᴒꜜᴡᴠͼⱱꜝᴟͼᴠᴢԝ꞊ᴒᴐᴡᴠͼᴤⱳꜝͼᴒᴥꜞᴒᴟ꞉ᴒꜜᴐᴒͼᴑᴟᴢⱲͼᴟᴒꞌԜᴡᴒᴑԓͼᴠᴒᴟ꞉ꜝᴢᴠԓͼᴢꜜᴒᴥꜞᴒᴐᴡᴒᴑͼԜᴑᴣᴒᴟᴠᴒͼ
ᴒᴣᴒꜜᴡᴠͼⱱꜝᴟͼᴡⱳᴒͼꜞᴢᴟꜞꜝᴠᴒͼꜝⱱͼᴟᴒⱲᴢꞌԜᴡꜝᴟᴦͼᴟᴒꜞꜝᴟᴡ꞉ꜜⱲ᷅
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ᴁⱳᴒͼꜝᴟᴑᴒᴟͼꜝⱱͼᴡⱳᴒͼᴠԜꜛꜞꞌᴒͼᴐꜝꞌꞌᴒᴐᴡ꞉ꜝꜜᴠͼᴤⱳᴒꜜͼꜛᴢꞌᴡ꞉ꜞꞌᴒͼᴠԜꜛꜞꞌᴒͼᴡᴦꜞᴒᴠͼԜᴟᴒͼᴐꜝꞌꞌᴒᴐᴡᴒᴑͼԜᴡͼᴡⱳᴒͼ
ᴠԜꜛᴒͼᴡ꞉ꜛᴒͼꜞꜝ꞉ꜜᴡͼ꞉ᴠͼᴢꜞᴑԜᴡᴒᴑͼᴡꜝͼᴐꜝᴟᴟᴒᴠꜞꜝꜜᴑͼᴡꜝͼᴡⱳᴒͼꜙԜԝꜝᴟԜᴡꜝᴟᴦꜚԜꜜᴢԜꞌ᷅
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ᴁⱳᴒͼᴠᴡᴢᴑᴦͼᴑԜᴦͼᴡⱳᴟꜝᴢⱲⱳͼᴤⱳ꞉ᴐⱳͼᴡᴟᴒԜᴡꜛᴒꜜᴡͼᴒꜛᴒᴟⱲᴒꜜᴡͼⱨⱬᴠͼԜᴟᴒͼᴑᴒⱱ꞉ꜜᴒᴑͼ꞉ᴠͼᴢꜞᴑԜᴡᴒᴑͼᴠꜝͼԜᴠͼᴡꜝͼ
ԝᴒͼᴐꜝꜜᴠ꞉ᴠᴡᴒꜜᴡͼᴤ꞉ᴡⱳͼꜝᴡⱳᴒᴟͼᴠᴒᴐᴡ꞉ꜝꜜᴠͼꜝⱱͼᴡⱳᴒͼꜞᴟꜝᴡꜝᴐꜝꞌ᷅
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ᴀᴢԝ꞊ᴒᴐᴡͼᴤ꞉ᴡⱳᴑᴟԜᴤԜꞌͼᴡᴒᴥᴡͼ꞉ᴠͼᴢꜞᴑԜᴡᴒᴑͼᴡꜝͼꜛꜝᴟᴒͼᴐꞌᴒԜᴟꞌᴦͼᴑ꞉ᴠᴡ꞉ꜜⱲᴢ꞉ᴠⱳͼԝᴒᴡᴤᴒᴒꜜͼ
ᴑ꞉ᴠᴐꜝꜜᴡ꞉ꜜᴢԜᴡ꞉ꜝꜜͼⱱᴟꜝꜛͼᴑꜝᴠ꞉ꜜⱲͼԜꜜᴑͼᴑ꞉ᴠᴐꜝꜜᴡ꞉ꜜᴢԜᴡ꞉ꜝꜜͼⱱᴟꜝꜛͼᴡⱳᴒͼᴠᴡᴢᴑᴦԓͼԜᴠͼᴤᴒꞌꞌͼԜᴠͼᴡꜝͼᴐꞌԜᴟ꞉ⱱᴦͼ
ᴡⱳԜᴡͼᴡⱳᴒͼᴢᴠᴒͼꜝⱱͼꜞᴟꜝⱳ꞉ԝ꞉ᴡ꞉ᴣᴒͼꜛᴒᴑ꞉ᴐԜᴡ꞉ꜝꜜᴠͼꜛԜᴦͼԝᴒͼⱲᴟꜝᴢꜜᴑᴠͼⱱꜝᴟͼᴤ꞉ᴡⱳᴑᴟԜᴤԜꞌͼԝᴦͼᴡⱳᴒͼ

Ⱬᴅ᷄᷉Ⱡ᷊᷇
ⱪꞌ꞉ꜜ꞉ᴐԜꞌͼᴁᴟ꞉Ԝꞌͼ͟ᴟꜝᴡꜝᴐꜝꞌⱡͼⱫᴅ᷄᷉Ⱡ᷊᷊᷇᷄᷇
ⱨꜛᴒꜜᴑꜛᴒꜜᴡͼ᷊᷅᷇ͼⱴ꞉ꜜԜꞌⱡͼ᷇ⱠͼꜗԜꜜᴢԜᴟᴦͼ᷉᷇᷈ⅎ
ⱪꜝꜜⱱ꞉ᴑᴒꜜᴡ꞉Ԝꞌ
͟ԜⱲᴒͼ᷈᷇᷉
ⱫᴦԜᴥͼⱪꜝᴟꜞ᷅
ⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟ᷅ͼᴁⱳᴒͼᴡᴒᴥᴡͼ꞉ᴠͼⱱᴢᴟᴡⱳᴒᴟͼᴢꜞᴑԜᴡᴒᴑͼᴡꜝͼᴐꞌԜᴟ꞉ⱱᴦͼᴡⱳԜᴡͼᴡⱳᴒͼⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟͼⱳԜᴠͼᴠꜝꞌᴒͼ
ᴑ꞉ᴠᴐᴟᴒᴡ꞉ꜝꜜͼᴡꜝͼᴤ꞉ᴡⱳᴑᴟԜᴤͼԜͼᴠᴢԝ꞊ᴒᴐᴡͼⱱꜝᴟͼᴠԜⱱᴒᴡᴦͼᴟᴒꞌԜᴡᴒᴑ꞉ᴠᴠᴢᴒᴠͼԜꜜᴑͼᴡⱳԜᴡͼᴡⱳᴒͼꜚᴒᴑ꞉ᴐԜꞌͼꜚꜝꜜ꞉ᴡꜝᴟͼ
꞉ᴠͼԜᴣԜ꞉ꞌԜԝꞌᴒͼⱱꜝᴟͼᴐꜝꜜᴠᴢꞌᴡԜᴡ꞉ꜝꜜ᷅
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ⱨͼꜛ꞉ꜜꜝᴟͼᴠꜞᴒꞌꞌ꞉ꜜⱲͼᴐꜝᴟᴟᴒᴐᴡ꞉ꜝꜜͼ꞉ᴠͼꜛԜᴑᴒͼᴐⱳԜꜜⱲ꞉ꜜⱲͼᶲꜛᴒᴑ꞉Ԝᴡ꞉ꜝꜜᴠᶳͼᴡꜝͼᶲꜛᴒᴑ꞉ᴐԜᴡ꞉ꜝꜜᴠᶳ
Protocol Amendments
Summary of Change(s) Since Last Version of Approved Protocol
Amendment Number
1.0
Amendment Date
14 December 2015
Global/Country/Site 
Specific
Global
Description of Change
Section(s) Affected by 
Change
ⱪꞌԜᴟ꞉ⱱ꞉ᴒᴠͼᴡⱳᴒͼԜᴐᴡᴢԜꞌͼ꞉ꜜⱲᴟᴒᴑ꞉ᴒꜜᴡᴠͼᴡⱳԜᴡͼԜᴟᴒͼᴟᴒⱱᴒᴟᴒꜜᴐᴒᴑͼ꞉ꜜͼᴡⱳᴒͼᴒᴥᴐ꞉ꜞ꞉ᴒꜜᴡͼꞌ꞉ᴠᴡ᷅
͟ԜⱲᴒͼ᷊ͼꜝⱱͼᴡⱳᴒͼᴀᴡᴢᴑᴦͼ
ᴀᴦꜜꜝꜞᴠ꞉ᴠԓͼⱷꜜԜᴐᴡ꞉ᴣᴒͼ
ⱷꜜⱲᴟᴒᴑ꞉ᴒꜜᴡᴠ
ⱪꞌԜᴟ꞉ⱱ꞉ᴒᴠͼᴡⱳᴒͼꜜԜᴡᴢᴟᴒͼꜝⱱͼᴡⱳᴒͼ͟ꜘͼԜꜜᴑͼ͟ⱫͼꜛᴒԜᴠᴢᴟᴒᴠͼꜝⱱͼᴒᴣԜꞌᴢԜᴡ꞉ꜝꜜ᷅ͼ
͟ԜⱲᴒͼ᷊᷈ͼꜝⱱͼᴡⱳᴒͼᴀᴡᴢᴑᴦͼ
ᴀᴦꜜꜝꜞᴠ꞉ᴠԓͼⱪᴟ꞉ᴡᴒᴟ꞉Ԝͼⱱꜝᴟͼ
ⱬᴣԜꞌᴢԜᴡ꞉ꜝꜜ
ⱫԜᴡԜͼⱱᴟꜝꜛͼᴡⱳᴒͼ⅍᷄ꜛꜝꜜᴡⱳͼᴠᴡᴢᴑᴦͼ꞉ᴠͼԜᴣԜ꞉ꞌԜԝꞌᴒͼԜꜜᴑͼꜛꜝᴟᴒͼᴟᴒꞌᴒᴣԜꜜᴡͼⱱꜝᴟͼᴡⱳ꞉ᴠͼꞌꜝꜜⱲ᷄ᴡᴒᴟꜛͼ
ꜞᴟꜝꜞⱳᴦꞌԜᴥ꞉ᴠͼᴡᴟ꞉Ԝꞌ᷅
͟ԜⱲᴒͼ᷉˲ԓͼᴀᴒᴐᴡ꞉ꜝꜜͼ᷈᷅᷾ͼᴀԜⱱᴒᴡᴦͼ
ϸԜᴡ꞉ꜝꜜԜꞌᴒͼⱱꜝᴟͼⱫᴅ᷄᷉Ⱡ᷊᷇
꜠ᴒᴢᴡᴟԜꞌ꞉ᴧ꞉ꜜⱲͼԜꜜᴡ꞉ԝꜝᴑᴦͼᴑԜᴡԜͼⱱᴟꜝꜛͼⱫᴅ᷄᷉Ⱡ᷊᷇᷄᷇᷉ͼ꞉ᴠͼꜜꜝᴤͼԜᴣԜ꞉ꞌԜԝꞌᴒ᷅ͼ
͟ԜⱲᴒͼ᷊᷈ԓͼᴀᴒᴐᴡ꞉ꜝꜜͼ᷈᷅⅍᷅᷉ͼ
ꜚᴢꞌᴡ꞉ꜞꞌᴒͼⱨᴠᴐᴒꜜᴑ꞉ꜜⱲͼⱫꜝᴠᴒͼ
ᴀᴡᴢᴑᴦͼ꞉ꜜͼⱶⱨⱬͼ͟Ԝᴡ꞉ᴒꜜᴡᴠͼ
ӿⱫᴅ᷄᷉Ⱡ᷊᷇᷄᷇᷉Ԑ
ⱪꞌԜᴟ꞉ⱱ꞉ᴒᴠͼᴡⱳᴒͼᴟᴒꜟᴢ꞉ᴟᴒꜛᴒꜜᴡᴠͼⱱꜝᴟͼᴒᴥᴡᴒꜜᴑᴒᴑͼᴟᴢꜜ᷄꞉ꜜͼꜞᴒᴟ꞉ꜝᴑᴠ᷅
͟ԜⱲᴒᴠͼ᷾ԓͼ᷈᷇ͼԜꜜᴑͼ᷈ⅎͼꜝⱱͼ
ᴀᴡᴢᴑᴦͼᴀᴦꜜꜝꜞᴠ꞉ᴠ
͟ԜⱲᴒͼ᷊᷾ԓͼᴀᴒᴐᴡ꞉ꜝꜜͼ᷊᷅᷈᷅᷈ԓͼ
꜡ᴣᴒᴟԜꞌꞌͼᴀᴡᴢᴑᴦͼⱫᴒᴠ꞉ⱲꜜͼԜꜜᴑͼ
͟ꞌԜꜜͼӿ꜡ᴣᴒᴟᴣ꞉ᴒᴤԐ
͟ԜⱲᴒͼ᷾˲ԓͼᴀᴒᴐᴡ꞉ꜝꜜͼ⅍᷅᷾᷅᷉ԓͼ
ⱶⱨⱬͼⱨᴡᴡԜᴐꞋͼⱷꜜⱱꜝᴟꜛԜᴡ꞉ꜝꜜͼ
ⱪꜝꞌꞌᴒᴐᴡ꞉ꜝꜜ
ⱨꜞꜞᴒꜜᴑ꞉ᴥͼ᷈ͼᴀᴡᴢᴑᴦͼ
ⱨᴐᴡ꞉ᴣ꞉ᴡ꞉ᴒᴠͼᴀᴐⱳᴒᴑᴢꞌᴒ
ⱪꞌԜᴟ꞉ⱱ꞉ᴒᴠͼᴡⱳᴒͼꜜᴢꜛԝᴒᴟͼꜝⱱͼᴠᴢԝ꞊ᴒᴐᴡᴠͼᴡⱳԜᴡͼꜛԜᴦͼԝᴒͼᴒꜜᴟꜝꞌꞌᴒᴑͼԝԜᴠᴒᴑͼꜝꜜͼᴡⱳᴒͼꜜᴢꜛԝᴒᴟͼꜝⱱͼ
ᴠᴢԝ꞊ᴒᴐᴡᴠͼᴒᴥꜞᴒᴐᴡᴒᴑͼᴡꜝͼᴐꜝꜛꜞꞌᴒᴡᴒ᷅
͟ԜⱲᴒͼ᷿ͼꜝⱱͼᴀᴡᴢᴑᴦͼᴀᴦꜜꜝꜞᴠ꞉ᴠ
͟ԜⱲᴒͼ᷊᷾ԓͼᴀᴒᴐᴡ꞉ꜝꜜͼ᷊᷅᷈᷅᷈ԓͼ
꜡ᴣᴒᴟԜꞌꞌͼᴀᴡᴢᴑᴦͼⱫᴒᴠ꞉ⱲꜜͼԜꜜᴑͼ
͟ꞌԜꜜͼӿ꜡ᴣᴒᴟᴣ꞉ᴒᴤԐ
ⱪꞌԜᴟ꞉ⱱ꞉ᴒᴠͼᴡⱳᴒͼⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟᶳᴠͼᴟꜝꞌᴒͼ꞉ꜜͼᴑ꞉ᴠᴐꜝꜜᴡ꞉ꜜᴢ꞉ꜜⱲͼᴠᴢԝ꞊ᴒᴐᴡͼᴑꜝᴠ꞉ꜜⱲ᷅
͟ԜⱲᴒͼ᷈᷉ͼꜝⱱͼᴀᴡᴢᴑᴦͼᴀᴦꜜꜝꜞᴠ꞉ᴠ
͟ԜⱲᴒͼ᷊˲ԓͼᴀᴒᴐᴡ꞉ꜝꜜͼ᷊᷊᷅᷈᷅᷉᷅ͼ
ⱷꜜᴑ꞉ᴣ꞉ᴑᴢԜꞌͼᴀᴡꜝꜞꜞ꞉ꜜⱲͼϸᴢꞌᴒᴠ
ⱪꞌԜᴟ꞉ⱱ꞉ᴒᴠᴡⱳᴒͼꜜᴢꜛԝᴒᴟͼꜝⱱͼᴠᴢԝ꞊ᴒᴐᴡᴠͼᴡⱳԜᴡͼꜛԜᴦͼԝᴒͼᴒꜜᴟꜝꞌꞌᴒᴑͼԝԜᴠᴒᴑͼꜝꜜͼᴡⱳᴒͼꜜᴢꜛԝᴒᴟͼꜝⱱͼ
ᴠᴢԝ꞊ᴒᴐᴡᴠͼᴒᴥꜞᴒᴐᴡᴒᴑͼᴡꜝͼᴐꜝꜛꜞꞌᴒᴡᴒ᷅
͟ԜⱲᴒͼ᷾᷇ԓͼᴀᴒᴐᴡ꞉ꜝꜜͼ᷾᷅᷈ͼᴀᴡᴢᴑᴦͼ
͟ꜝꜞᴢꞌԜᴡ꞉ꜝꜜ
͟ᴒᴟͼᴟᴒꜟᴢᴒᴠᴡͼԝᴦͼⱬᴢᴟꜝꜞᴒԜꜜͼϸᴒⱲᴢꞌԜᴡꜝᴟᴦͼⱨᴢᴡⱳꜝᴟ꞉ᴡ꞉ᴒᴠ᷅
͟ԜⱲᴒͼ᷿ͼꜝⱱͼᴀᴡᴢᴑᴦͼᴀᴦꜜꜝꜞᴠ꞉ᴠ
͟ԜⱲᴒͼ᷾᷇ԓͼᴀᴒᴐᴡ꞉ꜝꜜͼ᷾᷅᷈ͼᴀᴡᴢᴑᴦͼ
͟ꜝꜞᴢꞌԜᴡ꞉ꜝꜜ

Ⱬᴅ᷄᷉Ⱡ᷊᷇
ⱪꞌ꞉ꜜ꞉ᴐԜꞌͼᴁᴟ꞉Ԝꞌͼ͟ᴟꜝᴡꜝᴐꜝꞌⱡͼⱫᴅ᷄᷉Ⱡ᷊᷊᷇᷄᷇
ⱨꜛᴒꜜᴑꜛᴒꜜᴡͼ᷊᷅᷇ͼⱴ꞉ꜜԜꞌⱡͼ᷇ⱠͼꜗԜꜜᴢԜᴟᴦͼ᷉᷇᷈ⅎ
ⱪꜝꜜⱱ꞉ᴑᴒꜜᴡ꞉Ԝꞌ
͟ԜⱲᴒͼ᷊᷈᷇
ⱫᴦԜᴥͼⱪꜝᴟꜞ᷅
Protocol Amendments
Summary of Change(s) Since Last Version of Approved Protocol
Amendment Number
1.0
Amendment Date
14 December 2015
Global/Country/Site 
Specific
Global
Description of Change
Section(s) Affected by 
Change
ϸᴒⱱꞌᴒᴐᴡ꞉ᴣᴒͼꜝⱱͼᴐⱳԜꜜⱲᴒᴠͼᴡꜝͼᴡⱳᴒͼꜛԜꜜᴢⱱԜᴐᴡᴢᴟᴒͼꜝⱱͼⱷ͟ͼⱱᴟꜝꜛͼ᷈᷇᷇ͼꜛⱲ᷆ͼꜛꜙͼᴡꜝͼ᷿᷈᷇ͼꜛⱲ᷆ͼꜛꜙͼ
Ⱬᴅ᷉Ⱡ᷊᷇᷅
͟ԜⱲᴒͼⅎͼꜝⱱͼᴡⱳᴒͼᴀᴡᴢᴑᴦͼ
ᴀᴦꜜꜝꜞᴠ꞉ᴠ
͟ԜⱲᴒͼ᷾᷉ԓͼᴀᴒᴐᴡ꞉ꜝꜜͼ᷿᷅᷈ԓͼ
Ⱬᴒᴠᴐᴟ꞉ꜞᴡ꞉ꜝꜜͼꜝⱱͼᴁᴟᴒԜᴡꜛᴒꜜᴡᴠ
ⱪꞌԜᴟ꞉ⱱ꞉ᴒᴠͼᴡⱳᴒͼⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟᶳᴠͼᴟꜝꞌᴒͼ꞉ꜜͼԝᴟᴒԜꞋ꞉ꜜⱲͼᴡⱳᴒͼԝꞌ꞉ꜜᴑͼԜꜜᴑͼꜝԝᴡԜ꞉ꜜ꞉ꜜⱲͼᴡⱳᴒͼᴡᴟᴒԜᴡꜛᴒꜜᴡͼ
Ԝᴠᴠ꞉Ⱳꜜꜛᴒꜜᴡͼ꞉ꜜͼᴒꜛᴒᴟⱲᴒꜜᴐᴦͼᴠ꞉ᴡᴢԜᴡ꞉ꜝꜜᴠ᷅ͼ
ⱪꞌԜᴟ꞉ⱱ꞉ᴒᴠͼᴡⱳԜᴡͼⱫᴦԜᴥͼ͟ᴃͼᴤ꞉ꞌꞌͼꜝԝᴡԜ꞉ꜜͼᴡᴟᴒԜᴡꜛᴒꜜᴡͼԜᴠᴠ꞉ⱲꜜꜛᴒꜜᴡͼⱱꜝᴟͼᴟᴒⱲᴢꞌԜᴡꜝᴟᴦͼᴟᴒꜞꜝᴟᴡ꞉ꜜⱲͼ
ꜝⱱͼᴑᴟᴢⱲ᷄ᴟᴒꞌԜᴡᴒᴑԓͼᴠᴒᴟ꞉ꜝᴢᴠԓͼᴢꜜᴒᴥꜞᴒᴐᴡᴒᴑͼⱨⱬᴠ᷅
͟ԜⱲᴒͼ᷊᷾ԓͼᴀᴒᴐᴡ꞉ꜝꜜͼ᷿᷅᷾ͼ
Ⱪꞌ꞉ꜜᴑ꞉ꜜⱲͼԜꜜᴑͼᴂꜜԝꞌ꞉ꜜᴑ꞉ꜜⱲ
ⱪꞌԜᴟ꞉ⱱ꞉ᴒᴠͼᴡⱳᴒͼᴡ꞉ꜛ꞉ꜜⱲͼꜝⱱͼᴡⱳᴒͼᴒⱱⱱ꞉ᴐԜᴐᴦͼᴒᴣԜꞌᴢԜᴡ꞉ꜝꜜͼꜞᴒᴟ꞉ꜝᴑ᷅
͟ԜⱲᴒͼ᷈᷉ͼꜝⱱͼᴡⱳᴒͼᴀᴡᴢᴑᴦͼ
ᴀᴦꜜꜝꜞᴠ꞉ᴠ
͟ԜⱲᴒͼ᷾⅍ԓͼᴀᴒᴐᴡ꞉ꜝꜜͼ⅍᷅᷾᷅᷈ͼ
͟ᴟ꞉ꜛԜᴟᴦͼԜꜜᴑͼᴀᴒᴐꜝꜜᴑԜᴟᴦͼ
ⱬꜜᴑꜞꜝ꞉ꜜᴡᴠ
ⱪꜝᴟᴟᴒᴐᴡᴠͼᴡⱳᴒͼꜝᴟᴑᴒᴟͼꜝⱱͼᴠԜꜛꜞꞌᴒͼᴑᴟԜᴤᴠͼԜᴡͼᴡ꞉ꜛᴒͼꜞꜝ꞉ꜜᴡᴠͼᴤⱳᴒꜜͼꜛᴢꞌᴡ꞉ꜞꞌᴒͼᴠԜꜛꜞꞌᴒᴠͼԜᴟᴒͼ
ᴑᴟԜᴤꜜ᷅
͟ԜⱲᴒͼ᷿᷇ԓͼᴀᴒᴐᴡ꞉ꜝꜜͼ⅍᷅˲᷅᷈ͼ
ꜙԜԝꜝᴟԜᴡꜝᴟᴦͼ͟ԜᴟԜꜛᴒᴡᴒᴟᴠ
ⱪꞌԜᴟ꞉ⱱ꞉ᴒᴠͼᴡⱳᴒͼᴠᴡᴢᴑᴦͼᴑԜᴦͼᴡⱳᴟꜝᴢⱲⱳͼᴤⱳ꞉ᴐⱳͼᴁⱬⱨⱬᴠͼԜᴟᴒͼᴐԜꜞᴡᴢᴟᴒᴑͼᴡꜝͼԝᴒͼᴐꜝꜜᴠ꞉ᴠᴡᴒꜜᴡͼᴤ꞉ᴡⱳͼ
ꜝᴡⱳᴒᴟͼᴠᴒᴐᴡ꞉ꜝꜜᴠͼꜝⱱͼᴡⱳᴒͼꜞᴟꜝᴡꜝᴐꜝꞌ᷅ͼ
͟ԜⱲᴒͼ᷿᷿ԓͼᴀᴒᴐᴡ꞉ꜝꜜͼ⅍᷅᷈⅍᷿᷅᷈᷅ͼ
ᴁᴟᴒԜᴡꜛᴒꜜᴡͼⱬꜛᴒᴟⱲᴒꜜᴡͼ
ⱨᴑᴣᴒᴟᴠᴒͼⱬᴣᴒꜜᴡᴠͼӿᴁⱬⱨⱬᴠԐ
ⱪꞌԜᴟ꞉ⱱ꞉ᴒᴠͼᴡⱳᴒͼᴠᴡᴢᴑᴦͼᴑԜᴦͼᴡⱳᴟꜝᴢⱲⱳͼᴤⱳ꞉ᴐⱳͼᴁⱬⱨⱬᴠͼԜᴟᴒͼᴐԜꜞᴡᴢᴟᴒᴑͼᴡꜝͼԝᴒͼᴐꜝꜜᴠ꞉ᴠᴡᴒꜜᴡͼᴤ꞉ᴡⱳͼ
ꜝᴡⱳᴒᴟͼᴠᴒᴐᴡ꞉ꜝꜜᴠͼꜝⱱͼᴡⱳᴒͼꜞᴟꜝᴡꜝᴐꜝꞌ᷅
͟ԜⱲᴒͼ᷿⅍ԓͼᴀᴒᴐᴡ꞉ꜝꜜͼ⅍᷅᷈⅍᷅᷉᷅᷈ͼ
ꜚꜝꜜ꞉ᴡꜝᴟ꞉ꜜⱲͼꜝⱱͼⱨᴑᴣᴒᴟᴠᴒͼ
ⱬᴣᴒꜜᴡᴠ
ⱪꞌԜᴟ꞉ⱱ꞉ᴒᴠͼᴡⱳᴒͼⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟᶳᴠͼᴟꜝꞌᴒͼ꞉ꜜͼᴤ꞉ᴡⱳᴑᴟԜᴤ꞉ꜜⱲͼᴠᴢԝ꞊ᴒᴐᴡᴠͼⱱꜝᴟͼᴠԜⱱᴒᴡᴦͼᴟᴒꞌԜᴡᴒᴑͼᴟᴒԜᴠꜝꜜᴠ᷅
͟ᴟꜝᴣ꞉ᴑᴒᴠͼԝᴒᴡᴡᴒᴟͼᴑ꞉ᴠᴡ꞉ꜜᴐᴡ꞉ꜝꜜͼԝᴒᴡᴤᴒᴒꜜͼᴑ꞉ᴠᴐꜝꜜᴡ꞉ꜜᴢԜᴡ꞉ꜝꜜͼⱱᴟꜝꜛͼᴑꜝᴠ꞉ꜜⱲͼԜꜜᴑͼ
ᴑ꞉ᴠᴐꜝꜜᴡ꞉ꜜᴢԜᴡ꞉ꜝꜜͼⱱᴟꜝꜛͼᴠᴡᴢᴑᴦ᷅
ⱪꞌԜᴟ꞉ⱱ꞉ᴒᴠͼᴡⱳԜᴡͼᴢᴠᴒͼꜝⱱͼꜞᴟꜝⱳ꞉ԝ꞉ᴡ꞉ᴣᴒͼꜛᴒᴑ꞉ᴐԜᴡ꞉ꜝꜜᴠͼꜛԜᴦͼԝᴒͼⱲᴟꜝᴢꜜᴑᴠͼⱱꜝᴟͼᴤ꞉ᴡⱳᴑᴟԜᴤԜꞌͼԝᴦͼ
ⱷꜜᴣᴒᴠᴡ꞉ⱲԜᴡꜝᴟ᷅
͟ԜⱲᴒͼ⅍᷈ԓͼᴀᴒᴐᴡ꞉ꜝꜜͼ⅍᷅᷈ⅎͼ
ᴀᴢԝ꞊ᴒᴐᴡͼᴄ꞉ᴡⱳᴑᴟԜᴤԜꞌ
ⱪꞌԜᴟ꞉ⱱ꞉ᴒᴠͼᴡⱳᴒͼꜜԜᴡᴢᴟᴒͼꜝⱱͼᴡⱳᴒͼ͟ꜘͼԜᴠᴠᴒᴠᴠꜛᴒꜜᴡᴠͼᴡꜝͼԝᴒͼᴒᴣԜꞌᴢԜᴡᴒᴑͼ꞉ꜜͼᴡⱳ꞉ᴠͼᴠᴡᴢᴑᴦ᷅
͟ԜⱲᴒͼⅎ᷿ԓͼᴀᴒᴐᴡ꞉ꜝꜜͼⱠ᷿᷅᷅᷈ͼ
͟ⱳԜᴟꜛԜᴐꜝꞋ꞉ꜜᴒᴡ꞉ᴐͼ
ⱨᴠᴠᴒᴠᴠꜛᴒꜜᴡᴠ
ⱪꞌԜᴟ꞉ⱱ꞉ᴒᴠͼᴡⱳᴒͼꜜԜᴡᴢᴟᴒͼꜝⱱͼᴡⱳᴒͼ͟ⱫͼԜᴠᴠᴒᴠᴠꜛᴒꜜᴡᴠͼᴡꜝͼԝᴒͼᴒᴣԜꞌᴢԜᴡᴒᴑͼ꞉ꜜͼᴡⱳ꞉ᴠͼᴠᴡᴢᴑᴦ
͟ԜⱲᴒͼⅎ᷿ԓͼᴀᴒᴐᴡ꞉ꜝꜜͼⱠ᷿᷅᷅᷉ͼ
͟ⱳԜᴟꜛԜᴐꜝᴑᴦꜜԜꜛ꞉ᴐͼ
ⱨᴠᴠᴒᴠᴠꜛᴒꜜᴡᴠ
ꜚ꞉ꜜꜝᴟͼᴠꜞᴒꞌꞌ꞉ꜜⱲͼᴐꜝᴟᴟᴒᴐᴡ꞉ꜝꜜ᷅
͟ԜⱲᴒͼ᷿᷈ͼꜝⱱͼᴡⱳᴒͼᴀᴡᴢᴑᴦͼ
ᴀᴦꜜꜝꜞᴠ꞉ᴠ
͟ԜⱲᴒͼⅎ˲ԓͼᴀᴒᴐᴡ꞉ꜝꜜͼⱠ᷅ⅎͼᴀԜⱱᴒᴡᴦͼ
ⱨꜜԜꞌᴦᴠ꞉ᴠ

Ⱬᴅ᷄᷉Ⱡ᷊᷇
ⱪꞌ꞉ꜜ꞉ᴐԜꞌͼᴁᴟ꞉Ԝꞌͼ͟ᴟꜝᴡꜝᴐꜝꞌⱡͼⱫᴅ᷄᷉Ⱡ᷊᷊᷇᷄᷇
ⱨꜛᴒꜜᴑꜛᴒꜜᴡͼ᷊᷅᷇ͼⱴ꞉ꜜԜꞌⱡͼ᷇ⱠͼꜗԜꜜᴢԜᴟᴦ᷉᷇᷈ⅎ
ⱪꜝꜜⱱ꞉ᴑᴒꜜᴡ꞉Ԝꞌ
͟ԜⱲᴒͼ᷈᷇᷾
ⱫᴦԜᴥͼⱪꜝᴟꜞ᷅
Appendix 2
National Institute of Allergy and Infectious Diseases, 
Division of Microbiology and Infectious Diseases 
(DMID) Adult Toxicity Table (Modified) (US National 
Institutes of Health; National Institute of Allergy and 
Infectious Diseases)

DIVISION OF MICROBIOLOGY AND INFECTIOUS 
DISEASES (DMID) ADULT TOXICITY TABLE
NOVEMBER 2007
DRAFT"
"
Note:  The following toxicity table is a DRAFT and designed to provide general guidance 
on parameters for monitoring safety in clinical trials. This toxicity table is not comprehensive and 
should not be applied directly to all trials. "
""
When selecting a toxicity table, the following are some of the items that must be taken into 
consideration:"
""
‚
The population being studied "
o
Does the clinical trial evaluate healthy subjects, subjects with a particular disease 
or condition? "
‚
The stage of test article development "
o
Is the clinical trial a Phase I, II, III or IV?"
‚
The type of test article "
o
Does the clinical trial evaluate a drug, device, vaccine or other biologic agent? "
‚
The prior human and preclinical experience with the test article"
o
Are there any specific findings that require adjustment of the toxicity table? "
""
Single site clinical trials evaluating healthy subjects should conform to the laboratory normal 
values at the single site. Multi-center clinical trials should reconcile among their laboratory normal 
values when evaluating a healthy volunteer population."
""
Please confer with the DMID protocol team and DMID's Office of Clinical Research Affairs when 
selecting or developing a toxicity table for a DMID-sponsored trial."
"
Page 105
Ⱬᴅ᷄᷉Ⱡ᷊᷇
ⱪꞌ꞉ꜜ꞉ᴐԜꞌͼᴁᴟ꞉Ԝꞌͼ͟ᴟꜝᴡꜝᴐꜝꞌⱡͼⱫᴅ᷄᷉Ⱡ᷊᷊᷇᷄᷇
ⱨꜛᴒꜜᴑꜛᴒꜜᴡͼ᷊᷅᷇ⱴ꞉ꜜԜꞌⱡͼ᷇ⱠͼꜗԜꜜᴢԜᴟᴦ᷉᷇᷈ⅎ
ⱪꜝꜜⱱ꞉ᴑᴒꜜᴡ꞉Ԝꞌ
ⱫᴦԜᴥͼⱪꜝᴟꜞ᷅

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Page 106
';
&OLQLFDO7ULDO3URWRFRO';
$PHQGPHQW )LQDO-DQXDU\ 
&RQILGHQWLDO
'\D[&RUS

DIVISION OF MICROBIOLOGY AND INFECTIOUS 
DISEASES (DMID) ADULT TOXICITY TABLE
NOVEMBER 2007
DRAFT"
"
"
HEMATOLOGY"
"
"
"
Itcfg"3""
"
Itcfg"4""
"
Itcfg"5""
"
Itcfg"6""
"
Jgoqinqdkp"
"
;07"/"3207"io1fN"
"
:02""/";06io1fN"
"
"807"/"90;"io1fN"
"
>"807"io1fN"
"
Cduqnwvg"Pgwvtqrjkn"Eqwpv"
"
3222/37221oo5"
"
972/;;;1oo5"
"
722/96;1oo5"
"
>7221oo5"
"
Rncvgngvu"
"
97.222/
;;.;;;1oo5"
"
72.222/
96.;;;1oo5"
"
42.222/6;.;;;1oo5"
"
>42.2221oo5"
YDEu"
33.222/35.2221"
oo5"
35.222/"
37.222"1oo5"
37.222/"
52.2221oo5"
@52.222"qt"
>3.222"1oo5"
'"Rqn{oqtrjqpwengct"
Ngweqe{vgu"-"Dcpf"Egnnu"
"@":2'"
;2"Î";7'"
@;7'"
//////////"
"
"
Cdpqtocn"
Hkdtkpqigp"
Nqy<"
322/422"oi1fN""
"
Jkij<"
622/822"oi1fN"
Nqy<"
>322"oi1fN""
"
Jkij<"
@822"oi1fN"
Nqy<"
>"72"oi1fN"
"
"
""""//////////"
Hkdtkpqigp"
cuuqekcvgf"ykvj"
itquu"dnggfkpi"qt"
ykvj"
fkuugokpcvgf"
eqciwncvkqp"
"
Hkdtkp"Urnkv"Rtqfwev"
"
42/62"oei1on"
"
63/72"oei1on"
"
73/82"oei1on"
"
@"82"oei1on"
"
Rtqvjtqodkp""
Vkog"*RV+"
"
3023"/"3047"z"WNP"
"
3048/307"z"WNP"
"
3073"/502"z"WNP"
"
@5"z"WNP"
"
Cevkxcvgf"Rctvkcn"
Vjtqodqrncuvkp"*CRRV+"
"
3023"/3088"z"WNP"
"
3089"/"4055"z"
WNP"
"
4056"/"5"z"WNP"
"
@"5"z"WNP"
"
Ogvjgoqinqdkp"
"
702"/";0;"'"
"
3202"/"360;"'"
"
3702"/"3;0;'"
"
@"4202"'"
Page 107
Ⱬᴅ᷄᷉Ⱡ᷊᷇
ⱪꞌ꞉ꜜ꞉ᴐԜꞌͼᴁᴟ꞉Ԝꞌͼ͟ᴟꜝᴡꜝᴐꜝꞌⱡͼⱫᴅ᷄᷉Ⱡ᷊᷊᷇᷄᷇
ⱨꜛᴒꜜᴑꜛᴒꜜᴡͼ᷊᷅᷇ⱴ꞉ꜜԜꞌⱡͼ᷇ⱠͼꜗԜꜜᴢԜᴟᴦ᷉᷇᷈ⅎ
ⱪꜝꜜⱱ꞉ᴑᴒꜜᴡ꞉Ԝꞌ
ⱫᴦԜᴥͼⱪꜝᴟꜞ᷅

DIVISION OF MICROBIOLOGY AND INFECTIOUS 
DISEASES (DMID) ADULT TOXICITY TABLE
NOVEMBER 2007
DRAFT"
"
"
CHEMISTRIES"
""
"
Itcfg"3""
"
Itcfg"4""
"
Itcfg"5""
"
Itcfg"6""
"
J{rqpcvtgokc"
"
352/357"oGs1N"
"
"345/34;"
oGs1N"
"
338/344"oGs1N"
"
>"338"oGs1N"qt"
cdpqtocn"uqfkwo"
with"ogpvcn"
uvcvwu"ejcpigu"qt"
ugk¦wtgu"
"
J{rgtpcvtgokc"
"
368/372"oGs1N"
"
373/379"oGs1N"
"
37:/387"oGs1N"
"
@"387"oGs1N"qt"
cdpqtocn"uqfkwo"
with ogpvcn"
uvcvwu"ejcpigu"qt"
ugk¦wtgu"
"
J{rqmcngokc"
"
502"/"506"oGs1N"
"
407"/"40;"oGs1N"
"
402"/"406"oGs1N""
qt"kpvgpukxg"
tgrncegogpv"
vjgtcr{"qt"
jqurkvcnk¦cvkqp"
tgswktgf"
"
>"402"oGs1N qt"
cdpqtocn"
rqvcuukwowith"
"rctguku."kngwu"qt"
nkhg/vjtgcvgpkpi"
cttj{vjokc"
"
J{rgtmcngokc"
"
708"/"802"oGs1N"
"
803"/"807"oGs1N"
"
808"/"902"oGs1n"
"
@"902"oGs1N"
qt"cdpqtocn"
rqvcuukwo" with 
nkhg/vjtgcvgpkpi"
cttj{vjokc"
"
J{rqin{egokc"
"
77/86"oi1fN"
"
62/76"oi1fN"
"
52/5;"oi1fN"
"
>52"oi1fN"qt"
cdpqtocn"inwequg"
with"ogpvcn"
uvcvwu"ejcpigu"qt"
eqoc"
"
J{rgtin{egokc"
*pqphcuvkpi"cpf"pq"rtkqt"
fkcdgvgu+"
"
338"/"382"oi1fN"
"
383/"472"
oi1fN"
"
473"/"722"oi1fN"
"
@"722"oi1fN qt
cdpqtocn"inwequg"
with mgvqcekfquku"
"qt"ugk¦wtgu"
"
J{rqecnegokc"
*eqttgevgf"hqt"cndwokp+"
"
:06"/"90:"oi1fN"
"
909"/"902"oi1fN"
"
80;"/"803"oi1fN"
"
>"803"oi1fN"
qt"cdpqtocn"
ecnekwo"with"nkhg"
vjtgcvgpkpi"
cttj{vjokc"qt"
vgvcp{"
"
"
"
"
"
"
Page 108
Ⱬᴅ᷄᷉Ⱡ᷊᷇
ⱪꞌ꞉ꜜ꞉ᴐԜꞌͼᴁᴟ꞉Ԝꞌͼ͟ᴟꜝᴡꜝᴐꜝꞌⱡͼⱫᴅ᷄᷉Ⱡ᷊᷊᷇᷄᷇
ⱨꜛᴒꜜᴑꜛᴒꜜᴡͼ᷊᷅᷇ⱴ꞉ꜜԜꞌⱡͼ᷇ⱠͼꜗԜꜜᴢԜᴟᴦ᷉᷇᷈ⅎ
ⱪꜝꜜⱱ꞉ᴑᴒꜜᴡ꞉Ԝꞌ
ⱫᴦԜᴥͼⱪꜝᴟꜞ᷅

DIVISION OF MICROBIOLOGY AND INFECTIOUS 
DISEASES (DMID) ADULT TOXICITY TABLE
NOVEMBER 2007
DRAFT"
CHEMISTRIES (continued)"
"
"
Itcfg"3""
"
Itcfg"4""
"
Itcfg"5""
"
Itcfg"6""
"
J{rgtecnegokc"
*eqttgev"hqt"cndwokp+"
"
3208"/"3307"oi1fN"
"
3308"/"3407"
oi1fN"
"
3408"/"3507"oi1fN"
"
@"3507"oi1fN"qt
cdpqtocn"ecnekwo"
with nkhg"
vjtgcvgpkpi"
cttj{vjokc"
"
J{rqocipgugokc"
"
306"/"304"oGs1N"
"
303"/"20;"oGs1N"
"
20:"/"208"oGs1N"
"
>"208"oGs1N"qt
cdpqtocn"
ocipgukwo"with 
nkhg/vjtgcvgpkpi"
cttj{vjokc"
"
J{rqrjqurjcvgokc"
"
402"/"406"oi1fN"
"
307"/30;"oi1fN"
qt"
tgrncegogpv"Tz"
tgswktgf"
"
302"/306"oi1fN""
kpvgpukxg"vjgtcr{""
qt"
jqurkvcnk¦cvkqp"
tgswktgf"
"
>"302"oi1fN"qt"
cdpqtocn"
rjqurjcvg"with 
nkhg/vjtgcvgpkpi"
cttj{vjokc"
"
J{rgtdknktwdkpgokc"*yjgp"
ceeqorcpkgf"d{"cp{"kpetgcug"
kp"qvjgt"nkxgt"hwpevkqp"vguv+"
"
303"/">3047"z"WNP"
"
3047"/">307"z"
WNP"
"
307"Î"3097"z"WNP"
"
@"3097"z"WNP"
"
J{rgtdknktwdkpgokc"*yjgp"
qvjgt"nkxgt"hwpevkqp"ctg"kp"vjg""
pqtocn"tcpig+"
"
303"/">307"z"WNP"
"
307"/">402"z"
WNP"
"
402"Î"502"z"WNP"
"
@"502"z"WNP"
"
DWP"
"
3047"/"407"z"WNP"
"
408"/"7"z"WNP"
"
703"/"32"z"WNP"
"
@"32"z"WNP"
J{rgtwtkegokc"*wtke"cekf+"
907"Î"3202"oi1fN"
3203"Î"3402"
oi1fN"
3403"Î"3702"oi1fN"
@3702"oi1fN"
"
"
"
Etgcvkpkpg"
"
303"/"307"z"WNP""
"
308"/"502"z"WNP"
"
503"/"8"z"WNP"
"
@"8"z"WNP"qt"
fkcn{uku"tgswktgf"
Page 109
Ⱬᴅ᷄᷉Ⱡ᷊᷇
ⱪꞌ꞉ꜜ꞉ᴐԜꞌͼᴁᴟ꞉Ԝꞌͼ͟ᴟꜝᴡꜝᴐꜝꞌⱡͼⱫᴅ᷄᷉Ⱡ᷊᷊᷇᷄᷇
ⱨꜛᴒꜜᴑꜛᴒꜜᴡͼ᷊᷅᷇ⱴ꞉ꜜԜꞌⱡͼ᷇ⱠͼꜗԜꜜᴢԜᴟᴦ᷉᷇᷈ⅎ
ⱪꜝꜜⱱ꞉ᴑᴒꜜᴡ꞉Ԝꞌ
ⱫᴦԜᴥͼⱪꜝᴟꜞ᷅

DIVISION OF MICROBIOLOGY AND INFECTIOUS 
DISEASES (DMID) ADULT TOXICITY TABLE
NOVEMBER 2007
DRAFT"
"
"
ENZYMES
"
"
Itcfg"3""
"
Itcfg"4""
"
Itcfg"5""
"
Itcfg"6""
"
CUV"*UIQV+"
"
303"/">402"z"WNP"
"
402"Î">502"z"WNP"
"
502"Î":02"z"WNP"
"
@":"z"WNP"
"
CNV"*UIRV+"
"
303"/">402"z"WNP"
"
402"Î">502"z"WNP"
"
502"Î":02"z"WNP"
"
@":"z"WNP"
"
IIV"
"
303"/">402"z"WNP"
"
402"Î">502"z"WNP"
"
502"Î":02"z"WNP"
"
@":"z"WNP"
"
Cnmcnkpg"Rjqurjcvcug"
"
303"/">402"z"WNP"
"
402"Î">502"z"WNP"
"
502"Î":02"z"WNP"
"
@":"z"WNP"
"
Co{ncug"
"
303"/"307"z"WNP"
"
308"/"402"z"WNP"
"
403"/"702"z"WNP"
"
@"703"z"WNP"
Nkrcug""
"
303"/"307"z"WNP"
"
308"/"402"z"WNP"
"
403"/"702"z"WNP"
"
@"703"z"WNP"
"
"
URINALYSIS
"
"
Itcfg"3""
"
Itcfg"4""
"
Itcfg"5""
"
Itcfg"6""
Rtqvgkpwtkc"
"
3-"
"qt""
422"oi"/"3"io"
nquu1fc{"
"
4/5-""
qt""
3/"4"io"
nquu1fc{"
"
6-"
"qt""
4/507"io"nquu1fc{"
"
pgrjtqvke"
u{pftqog""
qt"
@"507"io"nquu1fc{"
Jgocvwtkc"
"
oketqueqrke"qpn{"
>32"tde1jrh"
"
itquu."pq"enqvu"
@32"tde1jrh"
"
itquu."ykvj"qt"
ykvjqwv"enqvu."QT"
tgf"dnqqf"egnn"ecuvu"
"
qduvtwevkxg"qt"
tgswktgf"
vtcpuhwukqp"
Page 110
Ⱬᴅ᷄᷉Ⱡ᷊᷇
ⱪꞌ꞉ꜜ꞉ᴐԜꞌͼᴁᴟ꞉Ԝꞌͼ͟ᴟꜝᴡꜝᴐꜝꞌⱡͼⱫᴅ᷄᷉Ⱡ᷊᷊᷇᷄᷇
ⱨꜛᴒꜜᴑꜛᴒꜜᴡͼ᷊᷅᷇ⱴ꞉ꜜԜꞌⱡͼ᷇ⱠͼꜗԜꜜᴢԜᴟᴦ᷉᷇᷈ⅎ
ⱪꜝꜜⱱ꞉ᴑᴒꜜᴡ꞉Ԝꞌ
ⱫᴦԜᴥͼⱪꜝᴟꜞ᷅

DIVISION OF MICROBIOLOGY AND INFECTIOUS 
DISEASES (DMID) ADULT TOXICITY TABLE
NOVEMBER 2007
DRAFT"
"
"
CARDIOVASCULAR"
"
"
Itcfg"3""
"
Itcfg"4""
"
Itcfg"5""
"
Itcfg"6""
"
Ectfkce"Tj{vjo"
"
"
"
cu{orvqocvke."
vtcpukgpv"ukipu."
pq"
Tz"tgswktgf"
"
tgewttgpv1rgtukuvgpv="
u{orvqocvke"Tz"
tgswktgf"
"
wpuvcdng"
f{ut{vjokc="
jqurkvcnk¦cvkqp"
cpf"vtgcvogpv"
tgswktgf"
"
J{rgtvgpukqp"
"
vtcpukgpv"kpetgcug"
@"42"oo1Ji="pq"
vtgcvogpv"
"
tgewttgpv."
ejtqpke"
kpetgcug"
"@"42oo1Ji0"
1vtgcvogpv"
tgswktgf"
"
cewvg"vtgcvogpv"
tgswktgf="qwvrcvkgpv"
vtgcvogpv"qt"
jqurkvcnk¦cvkqp"
rquukdng"
"
gpf"qticp"
fcocig"qt"
jqurkvcnk¦cvkqp"
tgswktgf"
"
J{rqvgpukqp"
"
vtcpukgpv"
qtvjquvcvke"
j{rqvgpukqp"ykvj"
jgctv"tcvg"kpetgcugf"
d{">42"dgcv1okp"qt"
fgetgcugf"d{">32"
oo"Ji"u{uvqnke"
DR."Pq"vtgcvogpv"
tgswktgf"
"
u{orvqou"fwg"
vq"qtvjquvcvke"
j{rqvgpukqp"qt"
DR"fgetgcugf"
d{">42"oo"Ji"
u{uvqnke="
eqttgevcdng"
ykvj"qtcn"hnwkf"
vtgcvogpv"
"
tgswktgu"KX"hnwkfu="
pq"jqurkvcnk¦cvkqp"
tgswktgf"
"
ogcp"ctvgtkcn"
rtguuwtg""
>82oo1"Ji qt"
gpf"qticp"
fcocig"qt"ujqem="""
tgswktgu"
jqurkvcnk¦cvkqp"
cpf"xcuqrtguuqt"
vtgcvogpv"
"
Rgtkectfkvku"
"
okpkocn"ghhwukqp"
"
oknf1oqfgtcvg"
cu{orvqocvke"
ghhwukqp."pq"
vtgcvogpv"
"
u{orvqocvke"
ghhwukqp="rckp="
GMI"ejcpigu"
"
vcorqpcfg="
rgtkectfkqegpvguku"
qt"uwtigt{"
tgswktgf"
"
Jgoqttjcig."Dnqqf"Nquu"
"
oketqueqrke1qeewnv"
"
oknf."pq"
vtcpuhwukqp"
"
itquu"dnqqf"nquu="
3/4"wpkvu"vtcpuhwugf"
"
ocuukxg"dnqqf"
nquu="@"5"wpkvu"
vtcpuhwugf"
Page 111
Ⱬᴅ᷄᷉Ⱡ᷊᷇
ⱪꞌ꞉ꜜ꞉ᴐԜꞌͼᴁᴟ꞉Ԝꞌͼ͟ᴟꜝᴡꜝᴐꜝꞌⱡͼⱫᴅ᷄᷉Ⱡ᷊᷊᷇᷄᷇
ⱨꜛᴒꜜᴑꜛᴒꜜᴡͼ᷊᷅᷇ⱴ꞉ꜜԜꞌⱡͼ᷇ⱠͼꜗԜꜜᴢԜᴟᴦ᷉᷇᷈ⅎ
ⱪꜝꜜⱱ꞉ᴑᴒꜜᴡ꞉Ԝꞌ
ⱫᴦԜᴥͼⱪꜝᴟꜞ᷅

DIVISION OF MICROBIOLOGY AND INFECTIOUS 
DISEASES (DMID) ADULT TOXICITY TABLE
NOVEMBER 2007
DRAFT"
"
RESPIRATORY
""
"
Itcfg"3""
"
Itcfg"4""
"
Itcfg"5""
"
Itcfg"6""
"
Eqwij""
"
vtcpukgpv/"pq"
vtgcvogpv"
"
rgtukuvgpv"
eqwij="
vtgcvogpv"
tgurqpukxg"
"
Rctqz{uocn"eqwij="
wpeqpvtqnngf"ykvj"
vtgcvogpv"
////////////////////"
"
Dtqpejqurcuo."Cewvg"
"
vtcpukgpv="pq"
vtgcvogpv="
92'"/":2'"HGX3 "
qh"rgcm"hnqy"
"
tgswktgu"
vtgcvogpv="
pqtocnk¦gu"ykvj"
dtqpejqfkncvqt="
HGX3"72'"/"
92'"
*qh"rgcm"hnqy+"
"
pq"pqtocnk¦cvkqp"
ykvj"
dtqpejqfkncvqt="
HGX3"47'"/"72'"
qh"rgcm"hnqy="qt""
tgvtcevkqpu"rtgugpv"
"
e{cpquku<"HGX3"
>"47'"
qh"rgcm"hnqy"qt"
kpvwdcvkqp"
pgeguuct{"
F{urpgc"
"
f{urpgc"qp"
gzgtvkqp"
f{urpgc"ykvj"
pqtocn"cevkxkv{"
f{urpgc"cv"tguv"
f{urpgc"tgswktkpi"
Qz{igp"vjgtcr{"
Page 112
Ⱬᴅ᷄᷉Ⱡ᷊᷇
ⱪꞌ꞉ꜜ꞉ᴐԜꞌͼᴁᴟ꞉Ԝꞌͼ͟ᴟꜝᴡꜝᴐꜝꞌⱡͼⱫᴅ᷄᷉Ⱡ᷊᷊᷇᷄᷇
ⱨꜛᴒꜜᴑꜛᴒꜜᴡͼ᷊᷅᷇ⱴ꞉ꜜԜꞌⱡͼ᷇ⱠͼꜗԜꜜᴢԜᴟᴦ᷉᷇᷈ⅎ
ⱪꜝꜜⱱ꞉ᴑᴒꜜᴡ꞉Ԝꞌ
ⱫᴦԜᴥͼⱪꜝᴟꜞ᷅

DIVISION OF MICROBIOLOGY AND INFECTIOUS 
DISEASES (DMID) ADULT TOXICITY TABLE
NOVEMBER 2007
DRAFT"
"
"
GASTROINTESTINAL"
"
"
Itcfg"3""
"
Itcfg"4""
"
Itcfg"5""
"
Itcfg"6""
"
Pcwugc"
"
oknf"qt"vtcpukgpv="
ockpvckpu"
tgcuqpcdng"kpvcmg"
"
oqfgtcvg"
fkueqohqtv="
kpvcmg"
fgetgcugf"
ukipkhkecpvn{="
uqog"cevkxkv{"
nkokvgf"
"
pq"ukipkhkecpv"
kpvcmg="tgswktgu"KX"
hnwkfu"
jqurkvcnk¦cvkqp"
tgswktgf="
"
Xqokvkpi"
"
3"grkuqfg"kp"46"
jqwtu"
4/7"grkuqfgu"kp"
46"jqwtu"
@8"grkuqfgu"kp"46"
jqwtu"qt"pggfkpi"
KX"hnwkfu"
"
"
"
rj{ukqnqike"
eqpugswgpegu"
tgswktkpi"
jqurkvcnk¦cvkqp"qt"
tgswktkpi"
rctgpvgtcn"
pwvtkvkqp"
"
Eqpuvkrcvkqp"
"
tgswktkpi"uvqqn"
uqhvgpgt"qt"fkgvct{"
oqfkhkecvkqp"
tgswktkpi"
nczcvkxgu"
qduvkrcvkqp"
tgswktkpi"ocpwcn"
gxcewcvkqp"qt"
gpgoc"
"
qduvtwevkqp"qt
vqzke"ogiceqnqp"
"
Fkcttjgc"
"
oknf"qt"vtcpukgpv="
5/6"nqqug"
uvqqnu1fc{"qt"oknf"
fkcttjgc"ncuv">"3"
yggm"
"
oqfgtcvg"qt"
rgtukuvgpv="7/9"
nqqug"uvqqnu1fc{"
qt"fkcttjgc"
ncuvkpi"@3"yggm"
@9"nqqug"uvqqnu1fc{"
qt"dnqqf{"fkcttjgc="
qt"qtvjquvcvke"
j{rqvgpukqp"qt"
gngevtqn{vg"
kodcncpeg"qt"@4N"
KX"hnwkfu"tgswktgf""
"
"
j{rqvgpukxg"
ujqem qt"
rj{ukqnqike"
eqpugswgpegu"
tgswktkpi"
jqurkvcnk¦cvkqp"""
"
Qtcn"Fkueqohqtv1F{urjcikc"
"
oknf"fkueqohqtv="
pq"fkhhkewnv{"
uycnnqykpi"
"
uqog"nkokvu"qp"
gcvkpi1ftkpmkpi"
"
gcvkpi1vcnmkpi"xgt{"
nkokvgf="wpcdng"vq"
uycnnqy"uqnkf"
hqqfu"
"
wpcdng"vq"ftkpm"
hnwkfu="tgswktgu"
KX"hnwkfu"
"
"
Page 113
Ⱬᴅ᷄᷉Ⱡ᷊᷇
ⱪꞌ꞉ꜜ꞉ᴐԜꞌͼᴁᴟ꞉Ԝꞌͼ͟ᴟꜝᴡꜝᴐꜝꞌⱡͼⱫᴅ᷄᷉Ⱡ᷊᷊᷇᷄᷇
ⱨꜛᴒꜜᴑꜛᴒꜜᴡͼ᷊᷅᷇ⱴ꞉ꜜԜꞌⱡͼ᷇ⱠͼꜗԜꜜᴢԜᴟᴦ᷉᷇᷈ⅎ
ⱪꜝꜜⱱ꞉ᴑᴒꜜᴡ꞉Ԝꞌ
ⱫᴦԜᴥͼⱪꜝᴟꜞ᷅

DIVISION OF MICROBIOLOGY AND INFECTIOUS 
DISEASES (DMID) ADULT TOXICITY TABLE
NOVEMBER 2007
DRAFT"
"
"
NEUROLOGICAL
""
"
Itcfg"3""
"
Itcfg"4""
"
Itcfg"5""
"
Itcfg"6""
"
Pgwtq/Egtgdgnnct"
"
unkijv"
kpeqqtfkpcvkqp"
f{ufkcfqejqmkpguku"
"
kpvgpvkqp"
vtgoqt."
f{uogvtkc."
unwttgf"urggej="
p{uvciowu"
"
nqeqoqvqt"cvczkc"
"
kpecrcekvcvgf"
"
Ru{ejkcvtke"
"
oknf"cpzkgv{"qt"
fgrtguukqp"
"
oqfgtcvg"
cpzkgv{"qt"
fgrtguukqp="
vjgtcr{"
tgswktgf="
ejcpig"kp"
pqtocn"tqwvkpg"
"
ugxgtg"oqqf"
ejcpigu"tgswktkpi""
vjgtcr{="qt"uwkekfcn"
kfgcvkqp=""qt"
ciitguukxg"kfgcvkqp"
"
cewvg"ru{ejquku"
tgswktkpi"
jqurkvcnk¦cvkqp=""
qt"uwkekfcn"
iguvwtg1cvvgorv"
qt"jcnnwekpcvkqpu"
"
Owueng"Uvtgpivj"
"
uwdlgevkxg"
ygcmpguu"
pq"qdlgevkxg"
u{orvqou1"ukipu"
"
oknf"qdlgevkxg""
ukipu1u{orvqou"
pq"fgetgcug"kp"
hwpevkqp"
"
qdlgevkxg"ygcmpguu"
hwpevkqp"nkokvgf"
"
rctcn{uku"
Rctguvjgukc"*dwtpkpi."vkpinkpi."
gve0+"
oknf"fkueqohqtv="
pq"vtgcvogpv""
tgswktgf"
oqfgtcvg"
fkueqohqtv="
pqp/pcteqvke"
cpcnigukc"
tgswktgf"
ugxgtg"fkueqohqtv="
qt"pcteqvke"
cpcnigukc"tgswktgf"
ykvj"u{orvqocvke"
kortqxgogpv"
kpecrcekvcvkpi="qt"
pqv"tgurqpukxg"vq"
pcteqvke"cpcnigukc"
Pgwtq/ugpuqt{"
oknf"korcktogpv"kp"
ugpucvkqp"
*fgetgcugf"
ugpucvkqp."g0i0."
xkdtcvqt{."rkprtkem."
jqv1eqnf"kp"itgcv"
vqgu+"kp"hqecn"ctgc"
qt"u{oogvtkecn"
fkuvtkdwvkqp="qt"
ejcpig"kp"vcuvg."
uognn."xkukqp"
cpf1qt"jgctkpi"
oqfgtcvg"
korcktogpv"
*oqf"fgetgcugf"
ugpucvkqp."g0i0."
xkdtcvqt{."
rkprtkem."
jqv1eqnf"vq"
cpmngu+"cpf1qt"
lqkpv"rqukvkqp"qt"
oknf"
korcktogpv"vjcv"
ku"pqv"
u{oogvtkecn"
ugxgtg"korcktogpv"
*fgetgcugf"qt"nquu"
qh"ugpucvkqp"vq"
mpggu"qt"ytkuvu+"qt"
nquu"qh"ugpucvkqp"qh"
cv"ngcuv"oqf"fgitgg"
kp"ownvkrng"
fkhhgtgpv"dqf{"
ctgcu"*k0g0."wrrgt"
cpf"nqygt"
gzvtgokvkgu+"
ugpuqt{"nquu"
kpxqnxgu"nkodu"
cpf"vtwpm="
rctcn{uku=""qt
ugk¦wtgu"
Page 114
Ⱬᴅ᷄᷉Ⱡ᷊᷇
ⱪꞌ꞉ꜜ꞉ᴐԜꞌͼᴁᴟ꞉Ԝꞌͼ͟ᴟꜝᴡꜝᴐꜝꞌⱡͼⱫᴅ᷄᷉Ⱡ᷊᷊᷇᷄᷇
ⱨꜛᴒꜜᴑꜛᴒꜜᴡͼ᷊᷅᷇ⱴ꞉ꜜԜꞌⱡͼ᷇ⱠͼꜗԜꜜᴢԜᴟᴦ᷉᷇᷈ⅎ
ⱪꜝꜜⱱ꞉ᴑᴒꜜᴡ꞉Ԝꞌ
ⱫᴦԜᴥͼⱪꜝᴟꜞ᷅

DIVISION OF MICROBIOLOGY AND INFECTIOUS 
DISEASES (DMID) ADULT TOXICITY TABLE
NOVEMBER 2007
DRAFT"
"
"
MUSCULOSKELATEL
"
"
Itcfg"3""
"
Itcfg"4""
"
Itcfg"5""
"
Itcfg"6""
Ctvjtcnikc"
*lqkpv"rckp+"
oknf"rckp"pqv"
kpvgthgtkpi"ykvj"
hwpevkqp"
oqfgtcvg"rckp."
cpcnigukeu"
cpf1qt"rckp"
kpvgthgtkpi"ykvj"
hwpevkqp"dwv"pqv"
ykvj"cevkxkvkgu"
qh"fckn{"nkxkpi"
ugxgtg"rckp="rckp"
cpf1qt"cpcnigukeu"
kpvgthgtkpi"ykvj"
cevkxkvkgu"qh"fckn{"
nkxkpi"
fkucdnkpi"rckp"
Ctvjtkvku"
oknf"rckp"ykvj"
kphncoocvkqp."
gt{vjgoc"qt"lqkpv"
uygnnkpi"Î"dwv"pqv"
kpvgthgtkpi"ykvj"
hwpevkqp"
oqfgtcvg"rckp"
ykvj"
kphncoocvkqp."
gt{vjgoc"qt"
lqkpv"uygnnkpi"Î"
kpvgthgtkpi"ykvj"
hwpevkqp."dwv"
pqv"ykvj"
cevkxkvkgu"qh"
fckn{"nkxkpi"
ugxgtg"rckp"ykvj"
kphncoocvkqp."
gt{vjgoc"qt"lqkpv"
uygnnkpi"Îcpf"
kpvgthgtkpi"ykvj"
cevkxkvkgu"qh"fckn{"
nkxkpi"
rgtocpgpv"cpf1qt"
fkucdnkpi"lqkpv"
fkuvtwevkqp"
O{cnikc"
o{cnikc" ykvj" pq"
nkokvcvkqp"qh""
cevkxkv{"
owueng"
vgpfgtpguu"*cv"
qvjgt"vjcp"
kplgevkqp"ukvg+"
qt"ykvj"
oqfgtcvg"
korcktogpv"qh"
cevkxkv{"
ugxgtg"owueng"
vgpfgtpguu"ykvj"
octmgf"korcktogpv"
qh"cevkxkv{"
htcpm"
o{qpgetquku"
"
"
"
"
"
"
"
"
"
"
"
"
"
"
"
"
"
"
"
"
"
"
Page 115
Ⱬᴅ᷄᷉Ⱡ᷊᷇
ⱪꞌ꞉ꜜ꞉ᴐԜꞌͼᴁᴟ꞉Ԝꞌͼ͟ᴟꜝᴡꜝᴐꜝꞌⱡͼⱫᴅ᷄᷉Ⱡ᷊᷊᷇᷄᷇
ⱨꜛᴒꜜᴑꜛᴒꜜᴡͼ᷊᷅᷇ⱴ꞉ꜜԜꞌⱡͼ᷇ⱠͼꜗԜꜜᴢԜᴟᴦ᷉᷇᷈ⅎ
ⱪꜝꜜⱱ꞉ᴑᴒꜜᴡ꞉Ԝꞌ
ⱫᴦԜᴥͼⱪꜝᴟꜞ᷅

DIVISION OF MICROBIOLOGY AND INFECTIOUS 
DISEASES (DMID) ADULT TOXICITY TABLE
NOVEMBER 2007
DRAFT"
"
SKIN"
"
"
Itcfg"3""
"
Itcfg"4""
"
Itcfg"5""
"
Itcfg"6""
Oweqewvcpgqwu"
gt{vjgoc="rtwtkvwu"
fkhhwug."ocewnq"
rcrwnct"tcuj."
ft{"
fguswcocvkqp"
xgukewncvkqp qt"
oqkuv"
fguswcocvkqp"qt"
wnegtcvkqp"
gzhqnkcvkxg"
fgtocvkvku."
oweqwu"
ogodtcpg"
kpxqnxgogpv qt"
gt{vjgoc."
ownvkhqtog"qt"
uwurgevgf"
Uvgxgpu/Lqjpuqp"
qt""pgetquku"
tgswktkpi"uwtigt{"
Kpfwtcvkqp"
< 37oo""
37/52"oo"
@52oo"
"
Gt{vjgoc"
< 37oo""
37/52"oo"
@52oo"
"
Gfgoc"
< 37oo""
37/52"oo"
@52oo"
"
Tcuj"cv"Kplgevkqp"Ukvg"
< 37oo""
37/52"oo"
@52oo"
"
Rtwtkvwu"
unkijv"kvejkpi"cv"
kplgevkqp"ukvg"
oqfgtcvg"
kvejkpi"cv"
kplgevkqp"
gzvtgokv{"
kvejkpi"qxgt"gpvktg"
dqf{"
"
"
"
"
SYSTEMIC"
"
Itcfg"3""
"
Itcfg"4""
"
Itcfg"5""
"
Itcfg"6""
"
Cnngtike"Tgcevkqp"
"
rtwtkvwu"ykvjqwv"
tcuj"
"
nqecnk¦gf"
wtvkectkc"
"
igpgtcnk¦gf"
wtvkectkc="
cpikqgfgoc"
"
cpcrj{nczku"
Jgcfcejg"
oknf."pq"vtgcvogpv"
tgswktgf"
vtcpukgpv."
oqfgtcvg="
vtgcvogpv"
tgswktgf"
ugxgtg="tgurqpfu"vq"
kpkvkcn"pcteqvke"
vjgtcr{"
kpvtcevcdng="
tgswktgu"tgrgcvgf"
pcteqvke"vjgtcr{"
"
Hgxgt<"qtcn"
"
5909"/"5:07"E"qt""
32202"/"32307"H"
"
5:08"/"5;07"E"qt"
32308"/"3240;"H"
"
5;08"/"6207"E"qt"
325"/"327"H"
"
@"62"E"qt"
@"327"H"
"
Hcvkiwg"
"
pqtocn"cevkxkv{"
tgfwegf">"6:"jqwtu"
"
"pqtocn"cevkxkv{"
fgetgcugf"47/"
72'"@"6:"jqwtu"
"
pqtocn"cevkxkv{"
fgetgcugf"@"72'"
ecpÓv"yqtm"
"
wpcdng"vq"ectg"hqt"
ugnh"
"
"
 
 
 
 
 
 
 
"
Page 116
Ⱬᴅ᷄᷉Ⱡ᷊᷇
ⱪꞌ꞉ꜜ꞉ᴐԜꞌͼᴁᴟ꞉Ԝꞌͼ͟ᴟꜝᴡꜝᴐꜝꞌⱡͼⱫᴅ᷄᷉Ⱡ᷊᷊᷇᷄᷇
ⱨꜛᴒꜜᴑꜛᴒꜜᴡͼ᷊᷅᷇ⱴ꞉ꜜԜꞌⱡͼ᷇ⱠͼꜗԜꜜᴢԜᴟᴦ᷉᷇᷈ⅎ
ⱪꜝꜜⱱ꞉ᴑᴒꜜᴡ꞉Ԝꞌ
ⱫᴦԜᴥͼⱪꜝᴟꜞ᷅

"
Appendix 3 
National Institute of Allergy and Infectious Diseases, 
Division of Microbiology and Infectious Diseases 
(DMID) Pediatric Toxicity Tables (Modified) (US 
National Institutes of Health; National Institute of 
Allergy and Infectious Diseases)
"
"
Page 117
Ⱬᴅ᷄᷉Ⱡ᷊᷇
ⱪꞌ꞉ꜜ꞉ᴐԜꞌͼᴁᴟ꞉Ԝꞌͼ͟ᴟꜝᴡꜝᴐꜝꞌⱡͼⱫᴅ᷄᷉Ⱡ᷊᷊᷇᷄᷇
ⱨꜛᴒꜜᴑꜛᴒꜜᴡͼ᷊᷅᷇ⱴ꞉ꜜԜꞌⱡͼ᷇ⱠͼꜗԜꜜᴢԜᴟᴦ᷉᷇᷈ⅎ
ⱪꜝꜜⱱ꞉ᴑᴒꜜᴡ꞉Ԝꞌ
ⱫᴦԜᴥͼⱪꜝᴟꜞ᷅

DIVISION OF MICROBIOLOGY AND INFECTIOUS 
DISEASES (DMID) PEDIATRIC  TOXICITY TABLES
NOVEMBER  2007 
DRAFT"
"
"
Note:  The following toxicity table is a DRAFT and designed to provide general guidance 
on parameters for monitoring safety in clinical trials. This toxicity table is not comprehensive and should 
not be applied directly to all trials. "
""
When selecting a toxicity table, the following are some of the items that must be taken into consideration:"
""
‚
The population being studied "
o
Does the clinical trial evaluate healthy subjects, subjects with a particular disease or 
condition? "
‚
The stage of test article development "
o
Is the clinical trial a Phase I (is it for the fisrt time in human subjects?) , II, III or IV?"
‚
The type of test article "
o
Does the clinical trial evaluate a drug, device, vaccine or other biologic agent? "
‚
The prior human and preclinical experience with the test article"
o
Are there any specific findings that require adjustment of the toxicity table? "
o
Has it been approved for this indication in adult population?"
""
Single site clinical trials evaluating healthy subjects should conform to the laboratory normal values at the 
single site. Multi-center clinical trials should reconcile among their laboratory normal values when 
evaluating a healthy volunteer population."
""
Please confer with the DMID protocol team and DMID's Office of Clinical Research Affairs when selecting 
or developing a toxicity table for a DMID-sponsored trial."
"
Page 118
Ⱬᴅ᷄᷉Ⱡ᷊᷇
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NOVEMBER  2007 
DRAFT"
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Page 121
Ⱬᴅ᷄᷉Ⱡ᷊᷇
ⱪꞌ꞉ꜜ꞉ᴐԜꞌͼᴁᴟ꞉Ԝꞌͼ͟ᴟꜝᴡꜝᴐꜝꞌⱡͼⱫᴅ᷄᷉Ⱡ᷊᷊᷇᷄᷇
ⱨꜛᴒꜜᴑꜛᴒꜜᴡͼ᷊᷅᷇ⱴ꞉ꜜԜꞌⱡͼ᷇ⱠͼꜗԜꜜᴢԜᴟᴦ᷉᷇᷈ⅎ
ⱪꜝꜜⱱ꞉ᴑᴒꜜᴡ꞉Ԝꞌ
ⱫᴦԜᴥͼⱪꜝᴟꜞ᷅

DIVISION OF MICROBIOLOGY AND INFECTIOUS 
DISEASES (DMID) PEDIATRIC  TOXICITY TABLES
NOVEMBER  2007 
DRAFT"
"
(Greater than 3 months of age) 
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Page 122
Ⱬᴅ᷄᷉Ⱡ᷊᷇
ⱪꞌ꞉ꜜ꞉ᴐԜꞌͼᴁᴟ꞉Ԝꞌͼ͟ᴟꜝᴡꜝᴐꜝꞌⱡͼⱫᴅ᷄᷉Ⱡ᷊᷊᷇᷄᷇
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ⱪꜝꜜⱱ꞉ᴑᴒꜜᴡ꞉Ԝꞌ
ⱫᴦԜᴥͼⱪꜝᴟꜞ᷅

DIVISION OF MICROBIOLOGY AND INFECTIOUS 
DISEASES (DMID) PEDIATRIC  TOXICITY TABLES
NOVEMBER  2007 
DRAFT"
 (Greater than 3 months of age)  
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Page 123
Ⱬᴅ᷄᷉Ⱡ᷊᷇
ⱪꞌ꞉ꜜ꞉ᴐԜꞌͼᴁᴟ꞉Ԝꞌͼ͟ᴟꜝᴡꜝᴐꜝꞌⱡͼⱫᴅ᷄᷉Ⱡ᷊᷊᷇᷄᷇
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ⱪꜝꜜⱱ꞉ᴑᴒꜜᴡ꞉Ԝꞌ
ⱫᴦԜᴥͼⱪꜝᴟꜞ᷅

DIVISION OF MICROBIOLOGY AND INFECTIOUS 
DISEASES (DMID) PEDIATRIC  TOXICITY TABLES
NOVEMBER  2007 
DRAFT"
(Greater than 3 months of age) 
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Page 124
Ⱬᴅ᷄᷉Ⱡ᷊᷇
ⱪꞌ꞉ꜜ꞉ᴐԜꞌͼᴁᴟ꞉Ԝꞌͼ͟ᴟꜝᴡꜝᴐꜝꞌⱡͼⱫᴅ᷄᷉Ⱡ᷊᷊᷇᷄᷇
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ⱪꜝꜜⱱ꞉ᴑᴒꜜᴡ꞉Ԝꞌ
ⱫᴦԜᴥͼⱪꜝᴟꜞ᷅

DIVISION OF MICROBIOLOGY AND INFECTIOUS 
DISEASES (DMID) PEDIATRIC  TOXICITY TABLES
NOVEMBER  2007 
DRAFT"
 (Greater than 3 months of age)  
"
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GRADE 3
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Page 125
Ⱬᴅ᷄᷉Ⱡ᷊᷇
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ⱨꜛᴒꜜᴑꜛᴒꜜᴡͼ᷊᷅᷇ⱴ꞉ꜜԜꞌⱡͼ᷇ⱠͼꜗԜꜜᴢԜᴟᴦ᷉᷇᷈ⅎ
ⱪꜝꜜⱱ꞉ᴑᴒꜜᴡ꞉Ԝꞌ
ⱫᴦԜᴥͼⱪꜝᴟꜞ᷅

DIVISION OF MICROBIOLOGY AND INFECTIOUS 
DISEASES (DMID) PEDIATRIC  TOXICITY TABLES
NOVEMBER  2007 
DRAFT"
"
 (Greater than 3 months of age)  
"
ELECTROLYTES"
GRADE 1
GRADE 2
GRADE 3
GRADE 4
J{rgtpcvtgokc"
>367/36;"oGs1N"
372/377"oGs1N"
@377"oGs1N"qt"
cdpqtocn"uqfkwo"
CPF"ogpvcn"uvcvwu"
ejcpigu"
J{rqpcvtgokc
"
352/357"oGs1N"
34;/346"oGs1N
>346"oGs1N"qt"
cdpqtocn"uqfkwo"
CPF"ogpvcn"uvcvwu"
ejcpigu
J{rgtmcngokc"
702/70;"oGs1N"
802/806"oGs1N"
807/902"oGs1N"
@902"oGs1N"qt"
cdpqtocn"rqvcuukwo"
CPF"ectfkce"
cttj{vjcokc"
J{rqmcngokc
502/5/7"oGs1N"
407/40;"oGs1N
402/406"oGs1N
>402"oGs1N"qt"
cdpqtocn"rqvcuukwo"
CPF"ectfkce"
cttj{vjokc
J{rgtecnegokc
3207/3304oi1fN"
3305/330;"oi1fN
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902/909"oi1fN"
802/80;"oi1fN"
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J{rqocipgugokc"
304/306"oGs1N"
20;/303"oGs1N"
208/20:"oGs1N"
>208"oGs1N"qt"
cdpqtocn"ocipgukwo"
CPF"ectfkce"
cttj{vjokc"
J{rqin{egokc"
77/87"oi1fN"
62/76"oi1fN"
52/5;"oi1fN"
>52"oi1fN"qt"
cdpqtocn"inwequg"
CPF"ogpvcn"uvcvwu"
ejcpigu"
J{rgtin{egokc"
338/37;"oi1fN"
382/46;"oi1fN"
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@622"oi1fN"qt"
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"
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Page 126
Ⱬᴅ᷄᷉Ⱡ᷊᷇
ⱪꞌ꞉ꜜ꞉ᴐԜꞌͼᴁᴟ꞉Ԝꞌͼ͟ᴟꜝᴡꜝᴐꜝꞌⱡͼⱫᴅ᷄᷉Ⱡ᷊᷊᷇᷄᷇
ⱨꜛᴒꜜᴑꜛᴒꜜᴡͼ᷊᷅᷇ⱴ꞉ꜜԜꞌⱡͼ᷇ⱠͼꜗԜꜜᴢԜᴟᴦ᷉᷇᷈ⅎ
ⱪꜝꜜⱱ꞉ᴑᴒꜜᴡ꞉Ԝꞌ
ⱫᴦԜᴥͼⱪꜝᴟꜞ᷅

DIVISION OF MICROBIOLOGY AND INFECTIOUS 
DISEASES (DMID) PEDIATRIC  TOXICITY TABLES
NOVEMBER  2007 
DRAFT"
egnnu1jrh"
egnnu1jrh"
"
Page 127
Ⱬᴅ᷄᷉Ⱡ᷊᷇
ⱪꞌ꞉ꜜ꞉ᴐԜꞌͼᴁᴟ꞉Ԝꞌͼ͟ᴟꜝᴡꜝᴐꜝꞌⱡͼⱫᴅ᷄᷉Ⱡ᷊᷊᷇᷄᷇
ⱨꜛᴒꜜᴑꜛᴒꜜᴡͼ᷊᷅᷇ⱴ꞉ꜜԜꞌⱡͼ᷇ⱠͼꜗԜꜜᴢԜᴟᴦ᷉᷇᷈ⅎ
ⱪꜝꜜⱱ꞉ᴑᴒꜜᴡ꞉Ԝꞌ
ⱫᴦԜᴥͼⱪꜝᴟꜞ᷅

DIVISION OF MICROBIOLOGY AND INFECTIOUS 
DISEASES (DMID) PEDIATRIC  TOXICITY TABLES
NOVEMBER  2007 
DRAFT"
"
 (Greater than 3 months of age) 
"
CENTRAL NERVOUS SYSTEM (CNS)
GRADE 1
GRADE 2
GRADE 3
GRADE 4
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"
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Page 128
Ⱬᴅ᷄᷉Ⱡ᷊᷇
ⱪꞌ꞉ꜜ꞉ᴐԜꞌͼᴁᴟ꞉Ԝꞌͼ͟ᴟꜝᴡꜝᴐꜝꞌⱡͼⱫᴅ᷄᷉Ⱡ᷊᷊᷇᷄᷇
ⱨꜛᴒꜜᴑꜛᴒꜜᴡͼ᷊᷅᷇ⱴ꞉ꜜԜꞌⱡͼ᷇ⱠͼꜗԜꜜᴢԜᴟᴦ᷉᷇᷈ⅎ
ⱪꜝꜜⱱ꞉ᴑᴒꜜᴡ꞉Ԝꞌ
ⱫᴦԜᴥͼⱪꜝᴟꜞ᷅

"
kphqtocvkqp0"Cp{"uwdlgev/tgrqtvgf"cvvcem"pqv"eqphktogf"d{"vjg"Kpxguvkicvqt"owuv"jcxg"cp"
cnvgtpcvg"CG"fkcipquku"tgeqtfgf0""Cnn"uwdlgev/tgrqtvgf"cpf"Kpxguvkicvqt/eqphktogf"JCG"
cvvcemu"yknn"dg"tgeqtfgf"kp"vjg"gETH0"
4
INVESTIGATOR ATTACK ASSESSMENT 
Vjg"Rtkpekrcn"Kpxguvkicvqt"hqt"c"uvwf{"ukvg"oc{"kfgpvkh{"c"rj{ukekcp"fgukipgg"vq"cuuguu"rcvkgpv"
u{orvqo"kphqtocvkqp"cpf"ocmg"cvvcem"fgvgtokpcvkqpu0"Ukvgu"ujqwnf"dg"nkokvgf"vq"vyq"
kpfkxkfwcnu"tgurqpukdng"hqt"cuuguukpi"cvvcemu."qpg"qh"vjgo"dgkpi"vjg"Rtkpekrcn"Kpxguvkicvqt0"
Cuuguuqtu"owuv"dg"gzrgtkgpegf"ykvj"JCG"cpf"hcoknkct"ykvj"vjg"uvwf{"uwdlgevÓu"fkugcug"
jkuvqt{0""
Vjg"cuuguuqt"owuv"tgxkgy"vjg"kphqtocvkqp"cpf"fgvgtokpg"yjgvjgt"vjg"gxgpv"ku"cp"cevwcn"cvvcem"
qt"pqv0"Kh"pggfgf."vjg"cuuguuqt"ecp"eqpvcev"vjg"uwdlgev"cpf1qt"ectgikxgt"vq"enctkh{"kphqtocvkqp"
qt"cum"hqt"cp{"cffkvkqpcn"fgvckn0"Vjg"fgvgtokpcvkqp"yknn"dg"fqewogpvgf"cnqpi"ykvj"vjg"fcvg"
cpf"vkog"vjg"fgvgtokpcvkqp"ycu"ocfg0"Cp{"gxgpv"fggogf"pqv"cp"cvvcem"owuv"dg"ceeqorcpkgf"
d{"cp"gzrncpcvkqp"cpf"cnvgtpcvkxg"fkcipquku"d{"vjg"cuuguuqt0""
Yjgp"tgxkgykpi"uwdlgev"kphqtocvkqp."vjg"cuuguuqt"yknn"hqnnqy"vjg"fghkpkvkqpu"qh"cp"cvvcem"cu"
qwvnkpgf"kp"vjgug"rtqegfwtgu"cpf."vcmkpi"cnn"cxckncdng"kphqtocvkqp"cdqwv"vjg"gxgpv"kpvq"
eqpukfgtcvkqp."yknn"fgvgtokpg"kh"kv"ku"c"eqphktogf"cvvcem0"Vjg"cuuguuogpv"qh"vjg"cvvcem"ku"vjg"
Kpxguvkicvqt"qt"fgukipggÓu"qyp."cpf"pqv"vjg"qrkpkqp"qh"vjg"uwdlgev."vjg"uwdlgevÓu"ectgikxgt"qt"
cp{"qvjgt"ukvg"rgtuqppgn0"Cuuguuqtu"oc{"eqpuwnv"ykvj"qpg"cpqvjgt"cdqwv"c"rctvkewnct"uwdlgevÓu"
cvvcem"dwv"qpn{"qpg"cuuguuqt"ocmgu"vjg"fqewogpvgf"fgvgtokpcvkqp0"Kv"ku"rquukdng"hqt"dqvj"vjg"
Rtkpekrcn"Kpxguvkicvqt"cpf"rj{ukekcp"fgukipgg"vq"cuuguu"fkhhgtgpv"cvvcemu"hqt"vjg"ucog"uwdlgev0"
Page 129
Ⱬᴅ᷄᷉Ⱡ᷊᷇
ⱪꞌ꞉ꜜ꞉ᴐԜꞌͼᴁᴟ꞉Ԝꞌͼ͟ᴟꜝᴡꜝᴐꜝꞌⱡͼⱫᴅ᷄᷉Ⱡ᷊᷊᷇᷄᷇
ⱨꜛᴒꜜᴑꜛᴒꜜᴡͼ᷊᷅᷇ⱴ꞉ꜜԜꞌⱡͼ᷇ⱠͼꜗԜꜜᴢԜᴟᴦ᷉᷇᷈ⅎ
ⱪꜝꜜⱱ꞉ᴑᴒꜜᴡ꞉Ԝꞌ
ⱫᴦԜᴥͼⱪꜝᴟꜞ᷅

DIVISION OF MICROBIOLOGY AND INFECTIOUS 
DISEASES (DMID) PEDIATRIC  TOXICITY TABLES
NOVEMBER  2007 
DRAFT"
 (Greater than 3 months of age)  
"
OTHER 
GRADE 1
GRADE 2
GRADE 3
GRADE 4
Cnngti{
Rtwtkvwu"ykvjqwv"Tcuj
Rtwtkvke"Tcuj
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0
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32305"Î"32602H
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Itgcvgt"vjcp"32602H
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62E"*32602H+"hqt"
nqpigt"vjcp"7"fc{u
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Tcuj"
Igpgtcnk¦gf"wtvkectkc
Uvgxgpu/Lqjpuqp"
U{pftqog"qt"Gt{vjgoc"
ownvkhqtog
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Rckphwn."fkhhkewnv{"
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"
"
"
Page 130
Ⱬᴅ᷄᷉Ⱡ᷊᷇
ⱪꞌ꞉ꜜ꞉ᴐԜꞌͼᴁᴟ꞉Ԝꞌͼ͟ᴟꜝᴡꜝᴐꜝꞌⱡͼⱫᴅ᷄᷉Ⱡ᷊᷊᷇᷄᷇
ⱨꜛᴒꜜᴑꜛᴒꜜᴡͼ᷊᷅᷇ⱴ꞉ꜜԜꞌⱡͼ᷇ⱠͼꜗԜꜜᴢԜᴟᴦ᷉᷇᷈ⅎ
ⱪꜝꜜⱱ꞉ᴑᴒꜜᴡ꞉Ԝꞌ
ⱫᴦԜᴥͼⱪꜝᴟꜞ᷅

"
Appendix 4 
HAE Attack Assessment and Reporting Procedures 
(HAARP) 
"
Page 131
Ⱬᴅ᷄᷉Ⱡ᷊᷇
ⱪꞌ꞉ꜜ꞉ᴐԜꞌͼᴁᴟ꞉Ԝꞌͼ͟ᴟꜝᴡꜝᴐꜝꞌⱡͼⱫᴅ᷄᷉Ⱡ᷊᷊᷇᷄᷇
ⱨꜛᴒꜜᴑꜛᴒꜜᴡͼ᷊᷅᷇ⱴ꞉ꜜԜꞌⱡͼ᷇ⱠͼꜗԜꜜᴢԜᴟᴦ᷉᷇᷈ⅎ
ⱪꜝꜜⱱ꞉ᴑᴒꜜᴡ꞉Ԝꞌ
ⱫᴦԜᴥͼⱪꜝᴟꜞ᷅

"
"
HAE Attack Assessment and Reporting Procedures 
(HAARP)
Title:
JCG"Cvvcem"Cuuguuogpv"cpf"Tgrqtvkpi"Rtqegfwtgu"*JCCTR+"
Product Name:
FZ/4;52"
Indication:
Rtgxgpvkqp"qh"cpikqgfgoc"cvvcemu"kp"rcvkgpvu"ykvj"JCG"
Sponsor:
F{cz"Eqtr0""
77"Pgvyqtm"Ftkxg"
Dwtnkpivqp."OC"23:25"
Original Date:
36"Ugrvgodgt"4237"
Version:
x302"
"
Confidentiality Statement
Vjku"fqewogpv"ku"vjg"rtqrgtv{"qh"F{cz"Eqtr0"Vjg"kphqtocvkqp"kp"vjku"fqewogpv"eqpvckpu"vtcfg"ugetgvu"cpf"
eqoogtekcn"kphqtocvkqp"vjcv"ctg"rtkxkngigf"qt"eqphkfgpvkcn"cpf"oc{"pqv"dg"fkuenqugf"ykvjqwv"vjg"gzrtguu"ytkvvgp"
rgtokuukqp"qh"F{cz"wpnguu"tgswktgf"d{"hgfgtcn"qt"uvcvg"ncy"qt"tgiwncvkqpu0"Cp{"rgtuqp"vq"yjqo"vjg"kphqtocvkqp"
ku"fkuenqugf"owuv"dg"kphqtogf"vjcv"vjg"kphqtocvkqp"ku"rtkxkngigf"qt"eqphkfgpvkcn"cpf"oc{"pqv"dg"hwtvjgt"fkuenqugf"
d{"vjgo0"Vjgug"tguvtkevkqpu"qp"fkuenquwtg"yknn"crrn{"gswcnn{"vq"cnn"hwvwtg"kphqtocvkqp"uwrrnkgf"vq"{qw"vjcv"ku"
kpfkecvgf"cu"rtkxkngigf"qt"eqphkfgpvkcn0"
"
Page 132
Ⱬᴅ᷄᷉Ⱡ᷊᷇
ⱪꞌ꞉ꜜ꞉ᴐԜꞌͼᴁᴟ꞉Ԝꞌͼ͟ᴟꜝᴡꜝᴐꜝꞌⱡͼⱫᴅ᷄᷉Ⱡ᷊᷊᷇᷄᷇
ⱨꜛᴒꜜᴑꜛᴒꜜᴡͼ᷊᷅᷇ⱴ꞉ꜜԜꞌⱡͼ᷇ⱠͼꜗԜꜜᴢԜᴟᴦ᷉᷇᷈ⅎ
ⱪꜝꜜⱱ꞉ᴑᴒꜜᴡ꞉Ԝꞌ
ⱫᴦԜᴥͼⱪꜝᴟꜞ᷅

"
TABLE OF CONTENTS
3 
RWTRQUG"000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000005 
4 
FGHKPKVKQP"QH"CP"CVVCEM"0000000000000000000000000000000000000000000000000000000000000000000000000000000000000005 
5 
TGRQTVKPI"CPF"CUUGUUOGPV"QH"CVVCEM"FCVC"0000000000000000000000000000000000000000000005 
503 
Uwdlgev/Tgrqtvgf"U{orvqou"000000000000000000000000000000000000000000000000000000000000000000000000000000000006 
50303 
Cvvcem"Kphqtocvkqp"000000000000000000000000000000000000000000000000000000000000000000000000000000000000000006 
50304 
Yqtugpkpi"U{orvqou"0000000000000000000000000000000000000000000000000000000000000000000000000000000000007 
50305 
Uwdlgev"Vtckpkpi"0000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000007 
50306 
Tgrqtvkpi"Ownvkrng"Cvvcemu00000000000000000000000000000000000000000000000000000000000000000000000000007 
50307 
Ectgikxgt"Tgrqtv"000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000007 
50308 
Uwdlgev"Eqpvcev"ykvj"Ukvgu"000000000000000000000000000000000000000000000000000000000000000000000000000007 
504 
Ukvg"Eqpvcev"ykvj"vjg"Uwdlgev"000000000000000000000000000000000000000000000000000000000000000000000000000000000007 
50403 
Tgxkgy"qh"uwdlgev"tgrqtv"qh"u{orvqou"00000000000000000000000000000000000000000000000000000000008 
50404 
Fqewogpvkpi"c"Tgrqtvgf"Cvvcem"000000000000000000000000000000000000000000000000000000000000000000008 
50405 
Ukvg"Vtckpkpi0000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000009 
505 
JCG"cvvcemu"cu"Cfxgtug"Gxgpvu"00000000000000000000000000000000000000000000000000000000000000000000000000000009 
6 
KPXGUVKICVQT"CVVCEM"CUUGUUOGPV"000000000000000000000000000000000000000000000000000000000000000000: 
"
"
Page 133
Ⱬᴅ᷄᷉Ⱡ᷊᷇
ⱪꞌ꞉ꜜ꞉ᴐԜꞌͼᴁᴟ꞉Ԝꞌͼ͟ᴟꜝᴡꜝᴐꜝꞌⱡͼⱫᴅ᷄᷉Ⱡ᷊᷊᷇᷄᷇
ⱨꜛᴒꜜᴑꜛᴒꜜᴡͼ᷊᷅᷇ⱴ꞉ꜜԜꞌⱡͼ᷇ⱠͼꜗԜꜜᴢԜᴟᴦ᷉᷇᷈ⅎ
ⱪꜝꜜⱱ꞉ᴑᴒꜜᴡ꞉Ԝꞌ
ⱫᴦԜᴥͼⱪꜝᴟꜞ᷅

"
1 
PURPOSE 
Vjku"fqewogpv"crrnkgu"vq"enkpkecn"vtkcnu"vjcv"kpxqnxg"kpxguvkicvqt"cflwfkecvkqp1cuuguuogpv"qh"
cpikqgfgoc"cvvcemu0"Vjg"rwtrqug"qh"vjku"fqewogpv"ku"vq"rtqxkfg"c"fghkpkvkqp"qh"cp"JCG"
cvvcem"cpf"vq"fghkpg"c"uvcpfctfk¦gf"ugv"qh"rtqegfwtgu"hqt"vjg"tgrqtvkpi"cpf"cuuguuogpv"qh"
gxgpvu"tgrqtvgf"d{"uwdlgevu"vq"fgvgtokpg"yjgvjgt"vjqug"gxgpvu"ctg"vtwg"JCG"cvvcemu0"
2
DEFINITION OF AN ATTACK
Vq"dg"eqphktogf"cu"cp"JCG"cvvcem."vjg"gxgpv"owuv"jcxg"u{orvqou"qt"ukipu"eqpukuvgpv"ykvj"
cp"cvvcem"kp"cv"ngcuv"qpg"qh"vjg"hqnnqykpi"nqecvkqpu<""
‚
Rgtkrjgtcn"cpikqgfgoc<"ewvcpgqwu"uygnnkpi"kpxqnxkpi"cp"gzvtgokv{."vjg"hceg."pgem."vqtuq."
cpf1qt"igpkvqwtkpct{"tgikqp"
‚
Cdfqokpcn"cpikqgfgoc<"cdfqokpcn"rckp."ykvj"qt"ykvjqwv"cdfqokpcn"fkuvgpvkqp."pcwugc."
xqokvkpi."qt"fkcttjgc"
‚
Nct{pigcn"cpikqgfgoc<"uvtkfqt."f{urpgc."fkhhkewnv{"urgcmkpi."fkhhkewnv{"uycnnqykpi."vjtqcv"
vkijvgpkpi."qt"uygnnkpi"qh"vjg"vqpiwg."rcncvg."wxwnc."qt"nct{pz"
Fgurkvg"vjg"rtgugpeg"qh"vjgug"u{orvqou."vjg"kpxguvkicvqt"oc{"uvknn"fgvgtokpg"enkpkecnn{"vjcv"
vjg"gxgpv"fkf"pqv"tgrtgugpv"cp"JCG"cvvcem"kh"vjgtg"ctg"hgcvwtgu"vjcv"uvtqpin{"tghwvg"uwej"c"
fkcipquku0"Hqt"gzcorng."vjg"tgrqtvgf"gxgpv"ku"ceeqorcpkgf"d{"u{orvqou"vjcv"ctg"pqv"
eqpukuvgpv"ykvj"cp"cvvcem"*g0i0."wtvkectkc+."vjg"tgrqtvgf"gxgpv"rgtukuvu"ygnn"dg{qpf"vjg"v{rkecn"
vkog"eqwtug"qh"cp"cvvcem"*g0i0."itgcvgt"vjcp"9"fc{u+."qt"vjgtg"ku"c"nkmgn{"cnvgtpcvg"gvkqnqi{"hqt"
vjg"gxgpv"*g0i0."vjg"uwdlgevÓu"cdfqokpcn"u{orvqou"ctg"cvvtkdwvcdng"vq"c"xktcn"icuvtqgpvgtkvku"
qwvdtgcm"kp"vjg"jqwugjqnf+0"
Vq"dg"eqwpvgf"cu"c"wpkswg"cvvcem"fkuvkpev"htqo"vjgkt"rtgxkqwu"cvvcem."vjg"pgy"u{orvqou"owuv"
qeewt"cv"ngcuv"46"jqwtu"chvgt"tguqnwvkqp"qh"vjg"rtkqt"cvvcemÓu"u{orvqou0""
Cvvcem"tguqnwvkqp"ku"fghkpgf"cu"vjg"uwdlgev"pq"nqpigt"jcxkpi"u{orvqou"qh"vjg"cvvcem0"
Rtqftqocn"u{orvqou"d{"vjgougnxgu"ctg"pqv"eqpukfgtgf"cp"cvvcem0"
Rcvkgpv"tgrqtv"qh"wug"qh"cewvg"JCG"cvvcem"vtgcvogpv"hqt"cp"cvvcem"d{"kvugnh"ku"pqv"eqphktocvkqp"
vjcv"cp"cvvcem"qeewttgf0"
3
REPORTING AND ASSESSMENT OF ATTACK DATA
Cv"uetggpkpi"hqt"crrnkecdng"enkpkecn"vtkcnu."uwdlgev"JCG"cvvcem"jkuvqt{"yknn"dg"eqnngevgf"d{"vjg"
ukvg"hqt"gpvt{"kpvq"vjg"enkpkecn"fcvcdcug0"Kphqtocvkqp"eqnngevgf"yknn"kpenwfg"cp{"rtkqt"jkuvqt{"qh"
nct{pigcn"cvvcemu."cvvcem"htgswgpe{."cxgtcig"ugxgtkv{."rtgfqokpcpv"nqecvkqp*u+."cxgtcig"
fwtcvkqp."cewvg"cvvcem"vjgtcr{"wug."cpf"jkuvqt{"qh"nqpi/vgto"rtqrj{nczku0"
Fwtkpi"vjg"tgngxcpv"uvwf{"rgtkqfu."cu"fghkpgf"kp"vjg"crrnkecdng"uvwf{"rtqvqeqn."uwdlgevu"*qt"
ectgikxgtu."hqt"uwdlgevu">"3:"{gctu"qnf+"yknn"dg"kpuvtwevgf"vq"eqpvcev"vjg"ukvg"ykvjkp"94"jqwtu"
qh"vjg"uvctv"qh"u{orvqou"qh"cp"cvvcem0"Kp"vjg"ukvwcvkqp"vjcv"c"uwdlgev"ku"kpecrcekvcvgf"cpf"ku"
"
Page 134
Ⱬᴅ᷄᷉Ⱡ᷊᷇
ⱪꞌ꞉ꜜ꞉ᴐԜꞌͼᴁᴟ꞉Ԝꞌͼ͟ᴟꜝᴡꜝᴐꜝꞌⱡͼⱫᴅ᷄᷉Ⱡ᷊᷊᷇᷄᷇
ⱨꜛᴒꜜᴑꜛᴒꜜᴡͼ᷊᷅᷇ⱴ꞉ꜜԜꞌⱡͼ᷇ⱠͼꜗԜꜜᴢԜᴟᴦ᷉᷇᷈ⅎ
ⱪꜝꜜⱱ꞉ᴑᴒꜜᴡ꞉Ԝꞌ
ⱫᴦԜᴥͼⱪꜝᴟꜞ᷅

"
wpcdng"vq"eqpvcev"vjg"ukvg."c"hcokn{"ogodgt"qt"qvjgt"kpfkxkfwcn"ykvj"fgvckngf"mpqyngfig"qh"
vjg"gxgpv"ecp"rtqxkfg"vjg"kphqtocvkqp0"Kh"fguktgf"d{"vjg"uwdlgev."ogoqt{"ckfu"oc{"dg"
rtqxkfgf"vq"cuukuv"kp"vtcemkpi"cp{"JCG"cvvcemu"uwdlgevÓu"gzrgtkgpeg0"Cp{"vqqnu"qt"fgxkegu"vjg"
uwdlgev"wugu"vq"vtcem"vjku"kphqtocvkqp"ctg"pqv"kpvgpfgf"vq"ugtxg"cu"uqwteg"fqewogpvu"hqt"vjg"
uvwf{0""
Ukvg"rgtuqppgn"yknn"tgxkgy"vjg"kphqtocvkqp"rtqxkfgf"d{"vjg"uwdlgev"qt"ectgikxgt"cpf"uqnkekv"
cffkvkqpcn"kphqtocvkqp"cu"pgeguuct{"vq"fqewogpv"vjg"cvvcem0""Kphqtocvkqp"fqewogpvgf"d{"vjg"
ukvg"yknn"dg"eqpukfgtgf"uqwteg"hqt"vjg"uvwf{0""
C"fgukipcvgf"kpfkxkfwcn"cv"vjg"ukvg"*vjg"eqnngevqt+"yknn"eqpvcev"vjg"uwdlgev"qt"ectgikxgt"qp"c"
tgiwnct"dcuku"cu"fghkpgf"kp"vjg"uvwf{"rtqvqeqn."tgictfnguu"qh"yjgvjgt"qt"pqv"vjg"uwdlgev"jcu"
tgrqtvgf"cp{"cvvcemu."kp"qtfgt"vq"uqnkekv"hqt"cp{"cvvcemu"vjcv"oc{"jcxg"qeewttgf"dwv"ygtg"pqv"
tgrqtvgf0"Kp"cffkvkqp."fwtkpi"gcej"uvwf{"xkukv."ukvg"rgtuqppgn"yknn"uqnkekv"hqt"cp{"pgy"cvvcem"
kphqtocvkqp"vjcv"ycu"pqv"rtqxkfgf"vjtqwij"rtgxkqwu"eqpvcev"ykvj"vjg"uwdlgev"qt"ectgikxgt0"
Vjg"Kpxguvkicvqt"qt"fgukipgg"*vjg"cuuguuqt+"yknn"tgxkgy"vjg"cvvcem"kphqtocvkqp"cpf"gxcnwcvg"kh"
vjg"gxgpv"tgrtgugpvu"c"eqphktogf"JCG"cvvcem0"Kh"pgeguuct{"hqt"vjg"gxcnwcvkqp."vjg"kpxguvkicvqt"
qt"fgukipgg"oc{"eqpvcev"vjg"uwdlgev"vq"tgegkxg"cffkvkqpcn"kphqtocvkqp0""
3.1 
Subject-Reported Symptoms 
Uwdlgevu"cpf"ectgikxgtu"ecp"wug"cp{"gzkuvkpi"ogvjqfu"d{"yjkej"vjg{"vtcem"kphqtocvkqp"cdqwv"
vjgkt"cvvcemu."qt."kh"tgswguvgf."ogoqt{"ckfu"ecp"dg"rtqxkfgf"d{"vjg"uvwf{"ukvg0"Jqygxgt."
uwdlgevu"*qt"c"ectgikxgt+"yknn"pggf"vq"vtcem"cvvcemu"kp"uwej"c"yc{"cu"vq"dg"cdng"vq"eqpvcev"vjg"
uvwf{"ukvg"cu"uqqp"cu"rquukdng."dwv"pqv"ncvgt"vjcp"94"jqwtu"*5"hwnn"fc{u+"chvgt"vjg"hktuv"
u{orvqou"crrgct."vq"tgrqtv"vjg"kphqtocvkqp0"
3.1.1
Attack Information
Vjg"hqnnqykpi"kphqtocvkqp"ujqwnf"dg"rtqxkfgf"d{"vjg"uwdlgev"*qt"ectgikxgt+"cv"vjg"vkog"vjg{"
ctg"tgrqtvkpi"cp"cvvcem"vq"vjg"ukvg<"
‚
Fcvg"cpf"vkog"u{orvqou"qh"cp"cvvcem"ygtg"hktuv"gzrgtkgpegf"
‚
Fguetkrvkqp"qh"u{orvqou"gzrgtkgpegf."kpenwfkpi"nqecvkqp*u+"
‚
Korcev"qp"cevkxkv{"cpf"yjgvjgt"cp{"cuukuvcpeg"qt"ogfkecn"kpvgtxgpvkqp"ycu"tgswktgf."
kpenwfkpi"jqurkvcnk¦cvkqpu"qt"gogtigpe{"fgrctvogpv"xkukvu"
‚
Cp{"ogfkecvkqpu"wugf"vq"vtgcv"vjg"cvvcem"
‚
Kh"vjg"cvvcem"tguqnxgf."fcvg"cpf"vkog"vjg"uwdlgev"ycu"pq"nqpigt"gzrgtkgpekpi"u{orvqou""
Uwdlgevu"fq"pqv"jcxg"vq"yckv"hqt"vjgkt"u{orvqou"vq"eqorngvgn{"tguqnxg"vq"tgrqtv"cp"cvvcem0"
Kphqtocvkqp"cdqwv"qpiqkpi"u{orvqou"ecp"dg"qdvckpgf"d{"vjg"ukvg"fwtkpi"vjg"ejgem/kp"ecnn"
cpf1"qt"cv"c"uejgfwngf"uvwf{"xkukv0"Uwdlgevu"ujqwnf"pqv"ykvjjqnf"qt"fgnc{"cp{"vtgcvogpv"vjg{"
yqwnf"pqtocnn{"tgegkxg"vq"vtgcv"vjgkt"cvvcem"kp"qtfgt"eqpvcev"vjg"ukvg0"
Page 135
Ⱬᴅ᷄᷉Ⱡ᷊᷇
ⱪꞌ꞉ꜜ꞉ᴐԜꞌͼᴁᴟ꞉Ԝꞌͼ͟ᴟꜝᴡꜝᴐꜝꞌⱡͼⱫᴅ᷄᷉Ⱡ᷊᷊᷇᷄᷇
ⱨꜛᴒꜜᴑꜛᴒꜜᴡͼ᷊᷅᷇ⱴ꞉ꜜԜꞌⱡͼ᷇ⱠͼꜗԜꜜᴢԜᴟᴦ᷉᷇᷈ⅎ
ⱪꜝꜜⱱ꞉ᴑᴒꜜᴡ꞉Ԝꞌ
ⱫᴦԜᴥͼⱪꜝᴟꜞ᷅

"
3.1.2
Worsening Symptoms
Vjg"ukvg"oc{"tgswguv"vjg"uwdlgev"ecnn"vjgo"dcem"kh"vjg{"gzrgtkgpeg"yqtugpkpi"u{orvqou"
cpf1"qt"pgy"u{orvqou"hqt"c"tgrqtvgf"cvvcem0"Qvjgtykug."vjg"pgy"kphqtocvkqp"yknn"dg"ecrvwtgf"
fwtkpi"vjg"pgzv"ejgem/kp"ecnn"qt"uejgfwngf"uvwf{"xkukv0"Uwdlgevu"oc{"eqpvcev"vjg"ukvg"qp"vjgkt"
qyp"vq"rtqxkfg"kphqtocvkqp"cdqwv"cp{"yqtugpkpi"u{orvqou0"
3.1.3
Subject Training
Fwtkpi"uetggpkpi."ukvg"rgtuqppgn"yknn"vtckp"uwdlgevu"qp"kfgpvkh{kpi"u{orvqou"qh"cp"cvvcem."vjg"
tgswktgogpvu"hqt"tgrqtvkpi"cvvcemu"cpf"vjg"kphqtocvkqp"vjg{"yknn"dg"gzrgevgf"vq"rtqxkfg0""Vjg"
rcvkgpv"yknn"eqphkto"vjgkt"wpfgtuvcpfkpi"qh"yjcv"ku"tgswktgf"qh"vjgo"hqt"tgrqtvkpi"cvvcemu"vq"
vjg"ukvg0""Ukvgu"yknn"cuuguu"vjg"uwdlgevÓu"eqornkcpeg"ykvj"vjg"tgrqtvkpi"tgswktgogpvu"
vjtqwijqwv"vjg"uvwf{"cpf"oc{"tgvtckp"vjg"uwdlgev"kh"pgeguuct{"kp"qtfgt"vq"ockpvckp"vjg"
kpvgitkv{"qh"vjg"fcvc"rtqxkfgf"vq"vjg"ukvg0"
3.1.4
Reporting Multiple Attacks
Kh"c"uwdlgev"gzrgtkgpegu"u{orvqou"vjg{"cvvtkdwvg"vq"oqtg"vjcp"qpg"wpkswg"cvvcem"vjg{"ecp"
tgrqtv"vjku"cu"ownvkrng"cvvcemu"vq"vjg"ukvg0""Dcugf"qp"vjg"fghkpkvkqp"qh"cp"cvvcem"cu"uvcvgf"kp"
Ugevkqp"4."kv"yknn"dg"vjg"fgvgtokpcvkqp"qh"vjg"kpxguvkicvqt"qt"fgukipgg"cu"vq"yjgvjgt"gxgpvu"
tgrqtvgf"cu"dgkpi"ugrctcvg"ctg"eqphktogf"cu"ugrctcvg"cvvcemu"qt"pqv0"
3.1.5
Caregiver Report
Fwtkpi"uetggpkpi."ukvg"rgtuqppgn"yknn"vtckp"uwdlgev"ectgikxgtu"*kh"crrnkecdng+"qp"kfgpvkh{kpi"
u{orvqou"qh"cp"cvvcem."vjg"tgswktgogpvu"hqt"tgrqtvkpi"cvvcemu"cpf"vjg"kphqtocvkqp"vjg{"yknn"
dg"gzrgevgf"vq"rtqxkfg0""Vjg"ectgikxgt"yknn"eqphkto"vjgkt"wpfgtuvcpfkpi"qh"yjcv"ku"tgswktgf"qh"
vjgo"hqt"tgrqtvkpi"cvvcemu"vq"vjg"ukvg0"Ukvgu"yknn"cuuguu"vjg"ectgikxgtÓu"eqornkcpeg"ykvj"vjg"
tgrqtvkpi"tgswktgogpvu"vjtqwijqwv"vjg"uvwf{"cpf"oc{"tgvtckp"vjg"ectgikxgt"kh"pgeguuct{"kp"
qtfgt"vq"ockpvckp"vjg"kpvgitkv{"qh"vjg"fcvc"rtqxkfgf"vq"vjg"ukvg0"
3.1.6
Subject Contact with Sites
Ukvg"rgtuqppgn"yknn"guvcdnkuj"c"tgeqoogpfgf"ogvjqf"cpf"vkog"ykpfqy"hqt"gcej"uwdlgev"vq"
eqpvcev"vjg"ukvg"vq"tgrqtv"cp{"u{orvqou"qh"cp"cvvcem0"Ukvgu"yknn"guvcdnkuj"c"rtkoct{"eqpvcev"
rgtuqp"cpf."kh"rquukdng."c"dcem/wr"rgtuqp."ykvj"eqpvcev"kphqtocvkqp0"Dcem/wr"rncpu."kpenwfkpi"
ecnn"dcemu"cpf1"qt"wug"qh"dcem/wr"eqpvcevu."ujqwnf"dg"guvcdnkujgf"kp"ecug"vjg"uwdlgev"ku"wpcdng"
vq"tgcej"uqogqpg"cv"vjg"ukvg0""
3.2 
Site Contact with the Subject 
Ukvgu"yknn"guvcdnkuj"c"tgeqoogpfgf"fc{"cpf"vkog"ykpfqy"hqt"ejgem/kp"ecnnu"dgvyggp"uvwf{"
xkukvu0"Vjg"fcvg"cpf"vkog"hqt"ejgem/kpu"ecp"dg"oqfkhkgf"dcugf"qp"yjgp"vjg"ncuv"eqpvcev"ykvj"
vjg"uwdlgev"ycu"ocfg."cu"qwvnkpgf"kp"vjg"uvwf{"rtqvqeqn0"Yjgp"vjg"ukvg"ku"eqpvcevgf"d{"c"
uwdlgev"tgrqtvkpi"u{orvqou"qh"cp"cvvcem"vjg"ukvg"ujqwnf"ocmg"uwtg"vjg{"jcxg"vjg"cdknkv{"vq"
tgeqtf"vjg"kphqtocvkqp"rtqxkfgf"kp"c"eqorngvg"cpf"ceewtcvg"yc{0"Dcem/wr"rncpu"ujqwnf"dg"
Page 136
Ⱬᴅ᷄᷉Ⱡ᷊᷇
ⱪꞌ꞉ꜜ꞉ᴐԜꞌͼᴁᴟ꞉Ԝꞌͼ͟ᴟꜝᴡꜝᴐꜝꞌⱡͼⱫᴅ᷄᷉Ⱡ᷊᷊᷇᷄᷇
ⱨꜛᴒꜜᴑꜛᴒꜜᴡͼ᷊᷅᷇ⱴ꞉ꜜԜꞌⱡͼ᷇ⱠͼꜗԜꜜᴢԜᴟᴦ᷉᷇᷈ⅎ
ⱪꜝꜜⱱ꞉ᴑᴒꜜᴡ꞉Ԝꞌ
ⱫᴦԜᴥͼⱪꜝᴟꜞ᷅

"
guvcdnkujgf"kp"ecug"vjg"uwdlgev"okuugu"c"ecnn"htqo"vjg"ukvg0"C"uvwf{"uejgfwng"hqt"gcej"uwdlgevÓu"
qp/ukvg"xkukvu"yknn"dg"rtqxkfgf"vq"vjg"uwdlgev"d{"vjg"ukvg0"
3.2.1
Review of subject report of symptoms
Fwtkpi"eqpvcev"ykvj"vjg"uwdlgev."yjgvjgt"uwdlgev/kpkvkcvgf"qt"c"tgiwnct"ejgem/kp."ukvg"
rgtuqppgn"ujqwnf"cum"vjg"uwdlgev"vq"rtqxkfg"vjgo"kphqtocvkqp"cdqwv"pgy"qt"qpiqkpi"JCG"
cvvcemu"gzrgtkgpegf0"
Vjg"ukvg"yknn"vt{"vq"qdvckp"cnn"kphqtocvkqp"pgeguuct{"vq"fqewogpv"vjg"cvvcem"eqorngvgn{0"
Okuukpi"kphqtocvkqp"oc{"korcev"vjg"cuuguuogpv"qh"cp{"cvvcem"cpf"ujqwnf"dg"cxqkfgf"
yjgpgxgt"rquukdng0"
3.2.2
Documenting a Reported Attack
Eqorngvg"cpf"ceewtcvg"fqewogpvcvkqp"qh"gcej"tgrqtvgf"cvvcem"ku"korqtvcpv"vq"ocmkpi"cp"
Kpxguvkicvqt"cuuguuogpv"qh"vjg"cvvcem0"Vjg"ukvg"ujqwnf"fqewogpv"vjg"hqnnqykpi"kphqtocvkqp"
cdqwv"gcej"cvvcem"tgrqtvgf"d{"vjg"uwdlgev"qt"ectgikxgt<""
‚
Fcvg"cpf"vkog"qh"eqpvcev"ykvj"vjg"uwdlgev"
‚
Fcvg"cpf"vkog"vjg"uwdlgev"hktuv"gzrgtkgpegf"u{orvqou"
‚
Fguetkrvkqp"qh"u{orvqou"gzrgtkgpegf."kpenwfkpi"nqecvkqp*u+"
‚
Korcev"qp"cevkxkv{"cpf"yjgvjgt"cp{"cuukuvcpeg"ycu"tgswktgf"
‚
Kh"vjg"cvvcem"jcu"tguqnxgf"qt"ku"qpiqkpi0""Kh"vjg"cvvcem"jcu"tguqnxgf."vjg"fcvg"cpf"vkog"vjg"
uwdlgev"ycu"pq"nqpigt"gzrgtkgpekpi"cp{"u{orvqou"qh"vjg"cvvcem""""
‚
Pcogu"qh"cp{"ogfkecvkqpu"wugf"vq"vtgcv"vjg"cvvcem"kpenwfkpi"JCG"cewvg"vjgtcr{"qt"qvjgt"
pqp/JCG"vtgcvogpvu"
‚
Kh"jqurkvcnk¦cvkqp"qeewttgf"
‚
Kh"c"vtkr"vq"vjg"gogtigpe{"fgrctvogpv"qeewttgf"
Cffkvkqpcn"rtqdkpi"swguvkqpu"cdqwv"yjcv"vjg"uwdlgev"gzrgtkgpegf"vq"fgvgtokpg<"
‚
Kh"vjg"uwdlgev"qpn{"gzrgtkgpegf"rtqftqocn"u{orvqou"
‚
Kh""vjg"uwdlgev"gzrgtkgpegf"cp{vjkpi"fkhhgtgpv"vjcp"vjgkt"v{rkecn"cvvcem"""
‚
Kh"vjgtg"ygtg"cp{"rquukdng"cnvgtpcvkxg"gvkqnqikgu"qh"vjg"u{orvqou0"Hqt"gzcorng."c"xktcn"
icuvtqgpvgtkvku"qwvdtgcm"kp"vjg"jqwugjqnf"eqwnf"gzrnckp"cdfqokpcn"u{orvqou""
Vjg"qxgtcnn"ugxgtkv{"qh"vjg"uwdlgevÓu"cvvcem"yknn"dg"fgvgtokpgf"d{"vjg"ukvg"wukpi"vjg"hqnnqykpi"
fghkpkvkqpu<"
/
Oknf<"Vtcpukgpv"qt"oknf"fkueqohqtv""
/
Oqfgtcvg<"Oknf"vq"oqfgtcvg"nkokvcvkqp"kp"cevkxkv{"/"uqog"cuukuvcpeg"pggfgf"
/
Ugxgtg<"Octmgf"nkokvcvkqp"kp"cevkxkv{."cuukuvcpeg"tgswktgf"
"
Page 137
Ⱬᴅ᷄᷉Ⱡ᷊᷇
ⱪꞌ꞉ꜜ꞉ᴐԜꞌͼᴁᴟ꞉Ԝꞌͼ͟ᴟꜝᴡꜝᴐꜝꞌⱡͼⱫᴅ᷄᷉Ⱡ᷊᷊᷇᷄᷇
ⱨꜛᴒꜜᴑꜛᴒꜜᴡͼ᷊᷅᷇ⱴ꞉ꜜԜꞌⱡͼ᷇ⱠͼꜗԜꜜᴢԜᴟᴦ᷉᷇᷈ⅎ
ⱪꜝꜜⱱ꞉ᴑᴒꜜᴡ꞉Ԝꞌ
ⱫᴦԜᴥͼⱪꜝᴟꜞ᷅

"
Vjg"ukvg"yknn"cnuq"fqewogpv"vjg"fcvg"cpf"vkog"qh"kpxguvkicvqt"qt"fgukipgg"tgxkgy."vjg"qhhkekcn"
fgukipcvkqp"qh"vjg"gxgpv"cu"cp"cvvcem"qt"pqv."cpf"kh"crrnkecdng."vjg"tgcuqp"yj{"cp"gxgpv"ku"pqv"
eqpukfgtgf"cp"cvvcem0""
Cnn"tgrqtvgf"cvvcemu"yknn"dg"gpvgtgf"d{"ukvg"rgtuqppgn"kpvq"vjg"gngevtqpke"ecug"tgrqtv"hqto"
*gETH+0"
3.2.3
Site Training
Ukvg"rgtuqppgn"tgurqpukdng"hqt"eqnngevkpi"cvvcem"kphqtocvkqp"cdqwv"uwdlgev"JCG"cvvcemu"yknn"
pggf"vq"rcuu"c"ÐEqnngevqtÑ"vtckpkpi"cuuguuogpv"eqxgtkpi"vjg"hqnnqykpi<"
‚
fghkpkvkqp"qh"cp"JCG"cvvcem"
‚
tgswktgogpvu"qh"uwdlgevu"cpf"ectgvcmgtu"hqt"tgrqtvkpi"cvvcemu"
‚
tgrqtvkpi"yqtugpkpi"u{orvqou"cpf"ownvkrng"cvvcemu"
‚
kphqtocvkqp"vq"dg"eqnngevgf"htqo"uwdlgevu"cpf"ectgikxgtu"cu"ygnn"cu"vjg"cffkvkqpcn"rtqdkpi"
swguvkqpu"vq"icvjgt"eqpvgzv"hqt"vjg"cvvcem"kphqtocvkqp"rtqxkfgf"
‚
cuuguuogpv"qh"cvvcem"ugxgtkv{"
‚
gpvt{"qh"vjg"cvvcem"fcvc"kpvq"vjg"gETH"
‚
tgrqtvkpi"JCG"cvvcemu"cu"cfxgtug"gxgpvu""
‚
tgswktgogpvu"hqt"Kpxguvkicvqt"cuuguuogpv"qh"cvvcemu"
Vtckpkpiu"yknn"dg"eqpfwevgf"rtkqt"vq"ukvgu"uetggpkpi"uwdlgevu0""Vtckpkpiu"yknn"dg"fqewogpvgf"
kp"vjg"Vtkcn"Ocuvgt"Hkng0"Kpxguvkicvqtu"cpf"fgukipggu"yknn"dg"vtckpgf"qp"vjgug"rtqegfwtgu"cu"
ygnn"cpf"owuv"rcuu"cp"ÐCuuguuqtÑ"vtckpkpi"kp"qtfgt"vq"qhhkekcnn{"cuuguu"cvvcemu"hqt"vjku"uvwf{0""
Cnn"tgurqpukdng"rgtuqpu"kpxqnxgf"kp"vjg"eqnngevkqp"qh"kphqtocvkqp"htqo"uwdlgevu"qt"cuuguukpi"
cvvcemu"owuv"dg"nkuvgf"qp"HFC"Hqto"37940"
3.3
HAE attacks as Adverse Events
Cv"vjg"vkog"qh"gcej"eqpvcev"cpf"uejgfwngf"uvwf{"xkukv."ukvg"rgtuqppgn"yknn"cum"kh"vjg"uwdlgev"
gzrgtkgpegf"cp{"cfxgtug"gxgpvu"qt"ejcpigu"vq"vjg"ogfkecvkqpu"vjg{"ctg"vcmkpi0"
JCG"cvvcemu"yknn"dg"ecrvwtgf"cu"CGu0""Cnn"CGu."tgictfnguu"qh"ugtkqwupguu."ugxgtkv{."qt"ecwucn"
tgncvkqpujkr"vq"uvwf{"ftwi."yknn"dg"tgeqtfgf"qp"vjg"CG"rcig"qh"vjg"gETH0"
Cp{"CG"tgrqtvgf"vq"vjg"ukvg"oggvkpi"etkvgtkc"hqt"c"ugtkqwu"cfxgtug"gxgpv"owuv"dg"tgrqtvgf"vq"
F{cz"wukpi"vjg"UCG"Tgrqtvkpi"Hqto"kp"vjg"GFE"u{uvgo"ykvjkp"46"jqwtu"qh"dgeqokpi"cyctg"
qh"vjg"gxgpv0""Hqt"cnn"ugtkqwu"cfxgtug"gxgpvu"vjcv"ctg"tgrqtvgf"cu"JCG"cvvcemu."vjg"Rtkpekrcn"
Kpxguvkicvqt"qt"rj{ukekcp"fgukipgg"yknn"tgxkgy"vjg"gxgpv"ykvjkp"46"jqwtu"qh"kpkvkcn"pqvkhkecvkqp"
cpf."kp"ceeqtfcpeg"ykvj"JCCTR."gxcnwcvg"kh"kv"tgrtgugpvgf"c"eqphktogf"JCG"cvvcem0"
Hqt"cnn"pqp/ugtkqwu"CGu"vjcv"ctg"tgrqtvgf"cu"JCG"cvvcemu."vjg"Rtkpekrcn"Kpxguvkicvqt"qt"
rj{ukekcp"fgukipgg"yknn"tgxkgy"vjg"gxgpv"ykvjkp"5"fc{u"qh"kpkvkcn"pqvkhkecvkqp"cpf."kp"
ceeqtfcpeg"ykvj"JCCTR."gxcnwcvg"kh"kv"tgrtgugpvgf"c"eqphktogf"JCG"cvvcem0"Kh"pgeguuct{"hqt"
vjg"gxcnwcvkqp."vjg"Kpxguvkicvqt"qt"fgukipgg"oc{"eqpvcev"vjg"uwdlgev"hqt"cffkvkqpcn"
0"
Page 138
Ⱬᴅ᷄᷉Ⱡ᷊᷇
ⱪꞌ꞉ꜜ꞉ᴐԜꞌͼᴁᴟ꞉Ԝꞌͼ͟ᴟꜝᴡꜝᴐꜝꞌⱡͼⱫᴅ᷄᷉Ⱡ᷊᷊᷇᷄᷇
ⱨꜛᴒꜜᴑꜛᴒꜜᴡͼ᷊᷅᷇ⱴ꞉ꜜԜꞌⱡͼ᷇ⱠͼꜗԜꜜᴢԜᴟᴦ᷉᷇᷈ⅎ
ⱪꜝꜜⱱ꞉ᴑᴒꜜᴡ꞉Ԝꞌ
ⱫᴦԜᴥͼⱪꜝᴟꜞ᷅

"
kphqtocvkqp0"Cp{"uwdlgev/tgrqtvgf"cvvcem"pqv"eqphktogf"d{"vjg"Kpxguvkicvqt"owuv"jcxg"cp"
cnvgtpcvg"CG"fkcipquku"tgeqtfgf0""Cnn"uwdlgev/tgrqtvgf"cpf"Kpxguvkicvqt/eqphktogf"JCG"
cvvcemu"yknn"dg"tgeqtfgf"kp"vjg"gETH0"
4
INVESTIGATOR ATTACK ASSESSMENT 
Vjg"Rtkpekrcn"Kpxguvkicvqt"hqt"c"uvwf{"ukvg"oc{"kfgpvkh{"c"rj{ukekcp"fgukipgg"vq"cuuguu"rcvkgpv"
u{orvqo"kphqtocvkqp"cpf"ocmg"cvvcem"fgvgtokpcvkqpu0"Ukvgu"ujqwnf"dg"nkokvgf"vq"vyq"
kpfkxkfwcnu"tgurqpukdng"hqt"cuuguukpi"cvvcemu."qpg"qh"vjgo"dgkpi"vjg"Rtkpekrcn"Kpxguvkicvqt0"
Cuuguuqtu"owuv"dg"gzrgtkgpegf"ykvj"JCG"cpf"hcoknkct"ykvj"vjg"uvwf{"uwdlgevÓu"fkugcug"
jkuvqt{0""
Vjg"cuuguuqt"owuv"tgxkgy"vjg"kphqtocvkqp"cpf"fgvgtokpg"yjgvjgt"vjg"gxgpv"ku"cp"cevwcn"cvvcem"
qt"pqv0"Kh"pggfgf."vjg"cuuguuqt"ecp"eqpvcev"vjg"uwdlgev"cpf1qt"ectgikxgt"vq"enctkh{"kphqtocvkqp"
qt"cum"hqt"cp{"cffkvkqpcn"fgvckn0"Vjg"fgvgtokpcvkqp"yknn"dg"fqewogpvgf"cnqpi"ykvj"vjg"fcvg"
cpf"vkog"vjg"fgvgtokpcvkqp"ycu"ocfg0"Cp{"gxgpv"fggogf"pqv"cp"cvvcem"owuv"dg"ceeqorcpkgf"
d{"cp"gzrncpcvkqp"cpf"cnvgtpcvkxg"fkcipquku"d{"vjg"cuuguuqt0""
Yjgp"tgxkgykpi"uwdlgev"kphqtocvkqp."vjg"cuuguuqt"yknn"hqnnqy"vjg"fghkpkvkqpu"qh"cp"cvvcem"cu"
qwvnkpgf"kp"vjgug"rtqegfwtgu"cpf."vcmkpi"cnn"cxckncdng"kphqtocvkqp"cdqwv"vjg"gxgpv"kpvq"
eqpukfgtcvkqp."yknn"fgvgtokpg"kh"kv"ku"c"eqphktogf"cvvcem0"Vjg"cuuguuogpv"qh"vjg"cvvcem"ku"vjg"
Kpxguvkicvqt"qt"fgukipggÓu"qyp."cpf"pqv"vjg"qrkpkqp"qh"vjg"uwdlgev."vjg"uwdlgevÓu"ectgikxgt"qt"
cp{"qvjgt"ukvg"rgtuqppgn0"Cuuguuqtu"oc{"eqpuwnv"ykvj"qpg"cpqvjgt"cdqwv"c"rctvkewnct"uwdlgevÓu"
cvvcem"dwv"qpn{"qpg"cuuguuqt"ocmgu"vjg"fqewogpvgf"fgvgtokpcvkqp0"Kv"ku"rquukdng"hqt"dqvj"vjg"
Rtkpekrcn"Kpxguvkicvqt"cpf"rj{ukekcp"fgukipgg"vq"cuuguu"fkhhgtgpv"cvvcemu"hqt"vjg"ucog"uwdlgev0"
"
Page 139
Ⱬᴅ᷄᷉Ⱡ᷊᷇
ⱪꞌ꞉ꜜ꞉ᴐԜꞌͼᴁᴟ꞉Ԝꞌͼ͟ᴟꜝᴡꜝᴐꜝꞌⱡͼⱫᴅ᷄᷉Ⱡ᷊᷊᷇᷄᷇
ⱨꜛᴒꜜᴑꜛᴒꜜᴡͼ᷊᷅᷇ⱴ꞉ꜜԜꞌⱡͼ᷇ⱠͼꜗԜꜜᴢԜᴟᴦ᷉᷇᷈ⅎ
ⱪꜝꜜⱱ꞉ᴑᴒꜜᴡ꞉Ԝꞌ
ⱫᴦԜᴥͼⱪꜝᴟꜞ᷅