An Open-Label, Single-Dose Study to Evaluate the Pharmacokinetics of MK-8527 in Participants With Moderate and Severe Renal Impairment
Phase: PHASE1
Conditions: Renal Impairment
Sponsor: Merck Sharp & Dohme LLC

Official Protocol Title:
NCT Number:  
    NCT06295796
Document Date:
An Open-Label, Single-Dose Study to Evaluate 
the Pharmacokinetics of MK-8527 in 
Participants with Moderate and Severe Renal 
Impairment 
11-Dec-2023

Page 1 
Clinical Protocol 
An Open-Label, Single-Dose Study to Evaluate the Pharmacokinetics of MK-8527 in 
Participants with Moderate and Severe Renal Impairment 
Celerion Project No.: CA42394 
Sponsor Project No.: MK-8527-008-00 
US FDA IND No.: 165,532 
Study Phase: Phase 1 
Final Protocol Date: 11 December 2023 
Good Clinical Practices (GCP) Statement 
This study is to be performed in full compliance with the protocol, GCP, and applicable 
regulatory requirements. All required study documentation will be archived as required by 
regulatory authorities. 
Confidentiality Statement 
This document is confidential. It contains proprietary information of Merck Sharp & 
Dohme LLC and/or Celerion. Any viewing or disclosure of such information that is not 
authorized in writing by Merck Sharp & Dohme LLC and/or Celerion is strictly prohibited. 
Such information may be used solely for the purpose of reviewing or performing this 
study. 
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PROTOCOL REVISION HISTORY 
Date/Name 
Description 
11Dec2023 
by 
 
Final Protocol 
 
 
 
 
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PRINCIPAL INVESTIGATOR – SIGNATORY 
 
An Open-Label, Single-Dose Study to Evaluate the Pharmacokinetics of MK-8527 in 
Participants with Moderate and Severe Renal Impairment 
 
If the protocol is executed using the Veeva platform, the e-signature page will be found at the 
end of the PDF document. 
 
Signature:   
 
Date: _________________ 
Printed name: 
 
Title: 
 
Address: 
 
 
 
 
 
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SPONSOR AND SPONSOR’S REPRESENTATIVE – SIGNATORY 
 
An Open-Label, Single-Dose Study to Evaluate the Pharmacokinetics of MK-8527 in 
Participants with Moderate and Severe Renal Impairment 
 
If the protocol is executed using the Veeva platform, the e-signature page will be found at the 
end of the PDF document. 
Merck Sharp & Dohme LLC (hereafter called the Sponsor or MSD) 
126 East Lincoln Avenue 
PO Box 2000 
Rahway, New Jersey 07065, USA 
 
Signature:   
 
Date: _________________ 
 
Principal Scientist 
Tel.: 
 
E-mail: 
 
 
 
 
 
PPD
PPD
PPD
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ADDITIONAL KEY CONTACTS FOR THE STUDY 
Sponsor Contact for Serious 
Adverse Event Reporting 
Details to be provided in the Investigator Site File 
 
 
Protocol Author 
 
Senior Scientist 
Celerion 
100 Alexis-Nihon Boulevard, Suite 360 
Montreal, Quebec H4M 2N8, Canada 
Tel.: 
 
E-mail: 
 
 
Certified Clinical Laboratory 
To be provided separately 
 
Bioanalytical Laboratory 
To be provided separately 
 
Laboratory for 
Immunophenotyping 
 
To be provided separately 
 
Pharmacokinetic and Statistical 
Analyses 
Celerion 
621 Rose Street 
Lincoln, Nebraska 68502, USA 
Tel.: +1 402 476-2811 
 
 
PPD
PPD
PPD
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TABLE OF CONTENTS 
PROTOCOL REVISION HISTORY ................................................................................... 2 
PRINCIPAL INVESTIGATOR – SIGNATORY ................................................................ 3 
SPONSOR AND SPONSOR’S REPRESENTATIVE – SIGNATORY ............................. 4 
ADDITIONAL KEY CONTACTS FOR THE STUDY ...................................................... 5 
TABLE OF CONTENTS ....................................................................................................... 6 
ABBREVIATIONS ............................................................................................................... 10 
1 PROTOCOL SUMMARY ............................................................................................. 12 
1.1 
Protocol Synopsis .................................................................................................... 12 
1.2 
Study Schema .......................................................................................................... 14 
1.3 
Schedule of Activities ............................................................................................. 15 
2 INTRODUCTION........................................................................................................... 17 
2.1 
MK-8527 ................................................................................................................. 17 
2.2 
Rationale .................................................................................................................. 18 
2.2.1 
Rationale for this Study and Study Design ............................................... 18 
2.2.2 
Rationale for the Dose Selection ............................................................... 18 
2.2.3 
Rationale for Endpoints ............................................................................ 18 
2.3 
Risks and/or Benefits to Participants ...................................................................... 19 
3 STUDY OBJECTIVES AND ENDPOINTS ................................................................. 20 
4 STUDY DESIGN ............................................................................................................. 22 
4.1 
Description of Study Design ................................................................................... 22 
4.1.1 
Confinement, Return Visits, and Follow-Up ............................................ 22 
4.1.2 
Study Duration .......................................................................................... 22 
4.2 
Beginning and End of Study ................................................................................... 23 
4.2.1 
Clinical Criteria for Early Study Termination .......................................... 23 
4.3 
Study Design/Dosing/Procedures Modifications Permitted Within Protocol 
Parameter ................................................................................................................. 23 
5 STUDY POPULATION ................................................................................................. 25 
5.1 
Inclusion Criteria ..................................................................................................... 25 
5.2 
Exclusion Criteria .................................................................................................... 27 
5.3 
Lifestyle Considerations .......................................................................................... 29 
5.3.1 
Meals and Dietary Restrictions ................................................................. 29 
5.3.1.1 
Meals ........................................................................................ 29 
5.3.1.2 
Dietary Restrictions .................................................................. 29 
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5.3.2 
Caffeine, Alcohol, and Tobacco Restrictions ........................................... 29 
5.3.3 
Activity Restrictions ................................................................................. 30 
5.3.4 
Contraception Requirements ..................................................................... 30 
5.3.4.1 
Definitions ................................................................................ 30 
5.3.4.2 
Guidance for Female Participants ............................................ 31 
5.3.4.3 
Guidance for Male Participants ................................................ 31 
6 STUDY TREATMENTS AND CONCOMITANT THERAPY ................................. 33 
6.1 
Description of Study Treatments ............................................................................. 33 
6.2 
Drug Supplies, Storage, and Accountability ........................................................... 34 
6.3 
Study Dose Modification ........................................................................................ 34 
6.3.1 
Stopping Rules .......................................................................................... 34 
6.4 
Participant Assignment and Randomization ........................................................... 34 
6.4.1 
Participant Identification Card .................................................................. 35 
6.5 
Blinding ................................................................................................................... 35 
6.6 
Study Treatment Compliance .................................................................................. 35 
6.7 
Concomitant Therapy .............................................................................................. 35 
7 DISCONTINUATION 
OF 
STUDY 
DRUG 
AND 
PARTICIPANT 
WITHDRAWAL ............................................................................................................. 37 
7.1 
Discontinuation of Study Drug ............................................................................... 37 
7.2 
Participant Withdrawal from the Study ................................................................... 37 
7.2.1 
Withdrawal From Future Biomedical Research ....................................... 37 
7.3 
Lost to Follow-up .................................................................................................... 38 
8 STUDY ASSESSMENTS AND PROCEDURES ......................................................... 39 
8.1 
Screening Assessments and Procedures .................................................................. 39 
8.1.1 
Screen Failures .......................................................................................... 39 
8.2 
Safety Assessments and Procedures ........................................................................ 40 
8.2.1 
Physical Examination................................................................................ 40 
8.2.2 
Vital Signs ................................................................................................. 40 
8.2.3 
Electrocardiograms ................................................................................... 40 
8.2.4 
Clinical Laboratory Assessments .............................................................. 41 
8.2.5 
Immunophenotyping ................................................................................. 41 
8.2.6 
Adverse Events and Serious Adverse Events ........................................... 42 
8.2.6.1 
Definition of Adverse Event .................................................... 42 
8.2.6.2 
Definition of Serious Adverse Event ....................................... 43 
8.2.6.3 
Monitoring ............................................................................... 44 
8.2.6.4 
Reporting .................................................................................. 44 
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8.2.6.5 
Reporting for SAEs .................................................................. 47 
8.2.7 
Additional Events Reported ...................................................................... 47 
8.2.8 
Events of Clinical Interest ......................................................................... 47 
8.2.9 
Treatment of Overdose ............................................................................. 48 
8.3 
Pharmacokinetic Assessments ................................................................................. 48 
8.3.1 
Blood Sampling and Processing ............................................................... 48 
8.3.2 
Plasma and PBMC Pharmacokinetic Parameters ..................................... 49 
8.3.3 
Urine Sampling and Processing ................................................................ 50 
8.3.4 
Urine Pharmacokinetic Parameters ........................................................... 50 
8.3.5 
Long Term Storage and Use ..................................................................... 50 
8.3.6 
Analytical Method .................................................................................... 51 
8.4 
Planned Exploratory Biomarker Research .............................................................. 51 
8.4.1 
Biomarkers ................................................................................................ 51 
8.4.1.1 
Planned Genetic Analysis ........................................................ 51 
8.4.1.1.1 
Planned Genetic Analysis Sample Collection ................. 51 
8.4.2 
Future Biomedical Research ..................................................................... 52 
8.4.2.1 
Future Biomedical Research Sample Collection...................... 52 
8.5 
Blood Volume Drawn for Study Assessments ........................................................ 53 
9 STATISTICAL CONSIDERATIONS .......................................................................... 54 
9.1 
Sample Size Determination ..................................................................................... 54 
9.2 
Population for Analyses .......................................................................................... 54 
9.3 
Statistical Analyses ................................................................................................. 54 
9.3.1 
Pharmacokinetic Analyses ........................................................................ 55 
9.3.1.1 
Descriptive Statistics ................................................................ 55 
9.3.1.2 
Renal Function Categorization ................................................. 55 
9.3.1.3 
Statistical Analyses for Plasma MK-8527 and PBMC 
MK-8527-TP ............................................................................ 56 
9.3.1.4 
Statistical Analysis for Urine MK-8527 .................................. 57 
9.3.1.5 
Multiplicity ............................................................................... 57 
9.3.2 
Safety Analyses ......................................................................................... 57 
9.3.3 
Interim Analysis ........................................................................................ 57 
10 STUDY ADMINISTRATION........................................................................................ 58 
10.1 Ethics ....................................................................................................................... 58 
10.1.1 
Institutional Review Board ....................................................................... 58 
10.1.2 
Ethical Conduct of the Study .................................................................... 58 
10.1.3 
Participant Informed Consent ................................................................... 58 
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10.1.3.1 General Informed Consent ....................................................... 58 
10.1.3.2 Consent and Collection of Specimens for Future 
Biomedical Research ................................................................ 59 
10.1.4 
Confidentiality .......................................................................................... 59 
10.2 Study Termination ................................................................................................... 59 
10.3 Data Management ................................................................................................... 59 
10.3.1 
Data Entry and Verification ...................................................................... 60 
10.3.2 
Data Validation ......................................................................................... 60 
10.3.3 
Database Lock ........................................................................................... 60 
10.4 Direct Access to Source Data/Documents .............................................................. 60 
10.5 Reporting of the Study ............................................................................................ 61 
10.5.1 
Case Report Forms .................................................................................... 61 
10.5.2 
Record Keeping ........................................................................................ 61 
10.5.3 
Report Format ........................................................................................... 61 
10.6 Publication Policy ................................................................................................... 61 
11 REFERENCES ................................................................................................................ 62 
12 APPENDICES ................................................................................................................. 63 
12.1 Appendix 1: Collection and Management of Specimens for Future 
Biomedical Research ............................................................................................... 63 
 
LIST OF TABLES 
Table 1: 
Study Drugs ................................................................................................... 33 
Table 2: 
Window for PK Blood Sample Collection .................................................... 49 
Table 3: 
Blood Volume during the Study .................................................................... 53 
 
LIST OF FIGURES 
Figure 1: 
Overall Study Workflow ................................................................................ 14 
Figure 2: 
Schematic of Study Design for Each Group .................................................. 14 
 
 
 
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ABBREVIATIONS 
Pharmacokinetic parameter abbreviations and definitions are found in Section 8.3.2 and 
Section 8.3.4 International units of measurement are not included in this list. 
AE 
Adverse event 
AIDS 
Acquired immunodeficiency syndrome 
ALT 
Alanine aminotransferase 
APaT 
All Participants as Treated 
AST 
Aspartate aminotransferase 
BMI 
Body mass index 
BSA 
Body surface area 
CFR 
Code of Federal Regulations 
CI 
Confidence interval 
CKD-EPI 
Chronic Kidney Disease Epidemiology Collaboration 
COVID-19 
Coronavirus disease-2019 
CRF 
Case report form 
CRU 
Clinical research unit 
CSR 
Clinical study report 
CV 
Coefficient of variation 
DMP 
Data Management Plan 
DNA 
Deoxyribonucleic acid 
ECG 
Electrocardiogram 
ECI 
Event of clinical interest 
eGFR 
Estimated glomerular filtration rate 
FBR 
Future Biomedical Research 
FDA 
Food and Drug Administration 
FSH 
Follicle-stimulating hormone 
GCP 
Good Clinical Practice 
GMR 
Geometric mean ratio 
HBsAg 
Hepatitis B surface antigen 
HCV 
Hepatitis C virus 
HIV 
Human immunodeficiency virus 
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IB 
Investigator’s Brochure 
ICF 
Informed Consent Form 
ICH 
International Council for Harmonisation 
IND 
Investigational New Drug 
IRB 
Institutional Review Board 
IUD 
Intrauterine device 
ln 
Natural logarithm 
LSM 
Least-squares mean 
No. 
Number 
PBMC 
Peripheral blood mononuclear cell 
PI 
Principal Investigator 
PK 
Pharmacokinetic(s) 
PP 
Per-Protocol 
PrEP 
Pre-exposure prophylaxis 
QA 
Quality Assurance 
QTcF 
Corrected value of the interval between the Q and T waves on the 
electrocardiogram tracing, corrected using Fridericia formula 
RI 
Renal impairment 
RNA 
Ribonucleic acid 
SAE 
Serious adverse event 
SAP 
Statistical analysis plan 
TEAE 
Treatment-emergent adverse event 
TP 
Triphosphate 
ULN 
Upper limit of normal 
US 
United States 
USA 
United States of America 
 
 
 
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1 
PROTOCOL SUMMARY 
1.1 
Protocol Synopsis 
Protocol Title: 
An Open-Label, Single-Dose Study to Evaluate the 
Pharmacokinetics of MK-8527 in Participants with Moderate and 
Severe Renal Impairment 
Short Title: 
MK-8527 Renal Impairment Study 
Compound: 
MK-8527 
Study Phase: 
Phase 1 
Study Objectives: 
Primary objective: 
• To evaluate the plasma pharmacokinetics (PK) of MK-8527 
in participants with moderate and severe renal impairment 
(RI) compared to healthy matched control participants. 
Estimation: In participants with moderate and severe RI, 
plasma PK (e.g., AUC0-inf, Cmax) of MK-8527 following a 
single 6 mg dose of MK-8527 will be estimated and 
compared to those observed in healthy matched control 
participants. 
Secondary objectives: 
• To evaluate the safety and tolerability of MK-8527 in 
participants with moderate and severe RI. 
• To evaluate the intracellular PK of MK-8527 triphosphate 
(MK-8527-TP) in peripheral blood mononuclear cells 
(PBMCs) in participants with moderate and severe RI 
compared to healthy matched control participants. 
Estimation: In participants with moderate and severe RI, 
intracellular PK (e.g., AUC0-inf, Cmax) of MK-8527-TP in 
PBMCs following a single 6 mg dose of MK-8527 will be 
estimated and compared to those observed in healthy matched 
control participants. 
Study Design: 
This is a multi-site, open-label, single-dose study to evaluate the 
effect of moderate and severe RI on the PK, safety, and 
tolerability of MK-8527. 
Participants will receive a single oral dose of MK-8527 on Day 1. 
PK sampling will be performed predose and up to 168 hours 
postdose for plasma MK-8527 and predose and up to 672 hours 
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postdose for PBMC MK-8527-TP. Urine will be collected 
predose and up to 48 hours postdose for MK-8527 PK. 
All participants who received the study drug (including 
participants who terminate the study early) will return to the 
clinical research unit (CRU) on Day 29 (±1 day) for follow-up 
procedures and to determine if any adverse event (AE) has 
occurred since the last study visit. 
Study Duration: 
The total planned study duration (from screening to follow-up) 
for each participant is approximately 8 weeks. 
Number of 
Participants: 
A total of approximately 18 adult male and female participants 
will be enrolled, with 6 participants with moderate RI, 
6 participants with severe RI, and 6 healthy matched control 
participants. 
Healthy control participants will be enrolled after all moderate 
and severe RI participants have been dosed and will be matched 
by the mean age (± 15 years), mean body mass index (BMI; 
± 3.5 kg/m2), and sex (± 2) of participants with moderate and 
severe RI. 
At least 1 participant of each sex will be enrolled in each group. 
Dosage, Dosage Form, 
Route, and Dose 
Regimen: 
All participants will receive a single oral dose of 6 mg MK-8527 
(1 x 1 mg capsule + 1 x 5 mg capsule) on Day 1. 
Key Assessments: 
Pharmacokinetics: 
The following PK parameters, as appropriate, will be calculated: 
MK-8527 in plasma: AUC0-last, AUC0-inf, Cmax, Tmax, t½, 
CL/F, and Vz/F. 
MK-8527-TP in PMBC: AUC0-last, AUC0-inf, Cmax, C168, 
C672, Tmax, and t½. 
MK-8527 in urine: Ae, CLr, and fe. 
Safety: 
Safety will be monitored through AEs, clinical laboratory tests, 
total lymphocytes and CD4+ T cell counts, vital signs, 12-lead 
electrocardiograms (ECGs), and physical examination. 
Treatment-emergent AEs (TEAEs) will be tabulated and 
summary statistics for the clinical laboratory tests, total 
lymphocytes and CD4+ T cell counts, vital signs, and 12-lead 
ECGs will be computed and provided, as deemed appropriate. 
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1.2 
Study Schema 
Figure 1: Overall Study Workflow 
 
Abbreviations: n = sample size, RI = renal impairment. 
 
Figure 2: Schematic of Study Design for Each Group 
 
a: 
All participants who received the study drug (including participants who terminate the study early) will 
return to the CRU on Day 29 (±1 day) for follow-up procedures and to determine if any AE has occurred 
since the last study visit. 
Abbreviations: AE = adverse event, CRU = clinical research unit, PK = pharmacokinetic(s). 
 
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1.3 
Schedule of Activities 
Study Procedures a 
Scr b 
Study Days 
Days → 
-1 
1 
2 
3 
4 
5 
6 
7 
8 
15 ±1 
22 ±1 
29 ±1 
Hours → 
C-I c 
0 
0.25 
0.5 
1 
1.5 
2 
4 
6 
8 12 24 48 72 96 120 
144 
168 
336 
504 
672 
Administrative Procedures 
Informed Consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Informed Consent for FBR 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Inclusion/Exclusion Criteria 
X 
X 
X d 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medical History 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Participant ID Card 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
 
 
 
Safety Evaluations 
Full Physical Examination 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
 
 
X e 
Height 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Weight 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Vital Signs (HR, BP, RR, and T) 
X 
 
X f 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
 
 
X e 
12-Lead ECG 
X 
 
X f 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
 
 
X e 
Hem, Chem g, and UA  
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
 
 
X e 
Pregnancy Test (♀ only) h 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Serum FSH (PMP ♀ only) 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Urine/Saliva Drug Screen 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Urine/Breath Alcohol Screen 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
HIV/Hepatitis Screen 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
COVID-19 Screen 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Blood for Immunophenotyping 
 
 
X d 
 
 
 
 
 
 
 
 
 
 
X 
 
 
 
 
X 
 
 
X e 
AE Monitoring 
X 
X 
Concomitant Medication Monitoring 
X 
X 
Study Drug Dosing / PK / Biomarkers 
Participant Assignment 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
MK-8527 Dosing 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Blood for MK-8527 PK 
 
 
X d 
X 
X 
X 
X 
X X X X 
X 
X 
X 
X 
X 
X 
 
X 
 
 
 
Blood for MK-8527-TP PK 
 
 
X d 
 
 
 
 
 
X 
 
 
X 
X 
X 
 
X 
X 
X 
X 
X 
X 
X 
Urine for MK-8527 PK 
 
 
X i 
 
 
 
 
 
 
 
 
Blood for Genetic Analysis 
 
 
X j 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Other Procedures 
Confinement in the CRU k 
 
X 
 
 
 
Visit and Return Visits 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
X 
X 
Follow-up 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X l 
 
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a 
For details on procedures, refer to Section 8. 
b 
Within 28 days prior to dosing. 
c 
Participants will be admitted to the CRU on Day -1, at the time indicated by the CRU. 
d 
To be performed prior to dosing. 
e 
To be performed on Day 29 (±1 day) or prior to early termination from the study. 
f 
To be performed within 3 hours prior to dosing. 
g 
Samples for serum chemistry will be obtained after a fast of at least 8 hours, however, in case of discontinuations or rechecks, participants may not have 
fasted for 8 hours prior to when the serum chemistry sample is taken. 
h 
Serum pregnancy test(s) will be performed at screening. Serum or urine pregnancy tests will be performed at all other scheduled time points. 
i 
Urine collection intervals are predose, 0-4 hours, 4-8 hours, 8-12 hours, 12-24 hours, and 24-48 hours postdose. Urine samples will be collected per schedule 
whenever possible, as some participants with RI may not be able to produce urine during each collection interval. 
j 
To be obtained predose on Day 1, but may be collected at the next scheduled blood draw, if needed. 
k 
As per site preference, participants may be confined longer at the discretion of the PI or designee, and/or confined for additional short periods throughout the 
study (e.g., to facilitate attendance at return visits). 
l 
All participants who received the study drug (including participants who terminate the study early) will return to the CRU on Day 29 (±1 day) for follow-up 
procedures and to determine if any AE has occurred since the last study visit. 
 
 
Abbreviations: ♀ = Females, AE = Adverse event(s), BP = Blood pressure, C-I = Check-in, Chem = Chemistry, COVID-19 = Coronavirus disease 2019, 
CRU = Clinical research unit, ECG = Electrocardiogram, FBR = Future biomedical research, FSH = Follicle-stimulating hormone, Hem = Hematology, 
HIV = Human immunodeficiency virus, HR = Heart rate, ID = Identification, PI = Principal Investigator, PK = Pharmacokinetics, PMP = Postmenopausal, 
RI = Renal impairment, RR = Respiratory rate, Scr = Screening, T = Temperature, UA = Urinalysis.  
 
 
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2 
INTRODUCTION 
2.1 
MK-8527 
Human immunodeficiency virus (HIV)-1 is the etiologic agent of acquired 
immunodeficiency syndrome (AIDS). While there are effective antiretroviral treatments for 
HIV-1, productive infection with HIV-1 results in the establishment of a life-long, persistent 
infection characterized by low level viremia even with therapy due to virus integration into 
the host. The estimated number of people living with HIV-1 worldwide was approximately 
39 million in 2022 (UNAIDS, 2023). Although effective antiretroviral therapy halts disease 
progression, reduces mortality, and decreases the likelihood of HIV-1 transmission, the 
incidence of new infections is still high, with an estimated 1.3 million people newly infected 
in 2022. Access to reliable and highly effective pre-exposure prophylaxis (PrEP) is crucial to 
reduce the rate of new HIV-1 infections, and there is a clear need for new, effective means of 
preventing HIV-1 infection with PrEP. An oral PrEP regimen that can be taken once monthly 
is viewed widely as a promising long-acting option for HIV PrEP due to the ease of 
implementation. An oral monthly dosing regimen is anticipated to improve adherence, 
thereby offering the potential to be highly effective in the prevention of new HIV-1 
infections. 
MK-8527 is a novel potent deoxyadenosine analog being developed for HIV-1 PrEP. 
MK-8527 is converted intracellularly to the active triphosphate anabolite (MK-8527-TP) that 
is highly potent and has a long t½, enabling monthly dosing. 
MK-8527 has been studied in 3 completed Phase 1 studies, 2 ongoing Phase 1 studies, and 
1 ongoing Phase 2 study. The completed studies were MK-8527-001 (a single ascending dose 
study in healthy male participants), MK-8527-002 (a single-dose study in treatment naïve 
participants with HIV-1), and MK-8527-003 (a multiple ascending dose study in male and 
female participants of non-childbearing potential). MK-8527-004 is an ongoing Phase 1 
study and is evaluating single doses at additional dose levels in treatment naïve participants 
with HIV-1. MK-8527-006 is a drug-drug interaction study between MK-8527 and the 
combination oral contraceptive levonorgestrel/ethinylestradiol. MK-8527-007 is a Phase 2 
study to evaluate once monthly MK-8527 in participants at low risk for HIV-1 infection. 
As of 15-Sep-2023, MK-8527 has been administered to a total of 101 study participants 
(70 healthy adults and 31 people living with HIV-1) and has generally been well tolerated 
following administration of single oral doses up to 200 mg and 3 weekly doses up to 40 mg. 
MK-8527 has also shown efficacy in reduction of viral load as monotherapy in treatment 
naïve HIV-1 infected individuals with single doses as low as 0.5 mg. 
Following oral administration, MK-8527 was rapidly absorbed with a median Tmax of 0.5 to 
1 hour. Plasma concentrations decreased in a biphasic manner with t½ of approximately 36 to 
81 hours and exposures appeared to increase in an approximately dose-proportional manner. 
The active MK-8527-TP moiety reached intracellular Cmax at a median Tmax of 10 to 
48 hours and the concentrations in PBMC declined with a t½ of approximately 94 to 
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291 hours across doses. MK-8527-TP exposures showed less than dose-proportional 
increases over the dose range studied. 
In clinical studies, the most frequently reported AEs were headache and nasopharyngitis, 
with all MK-8527-related AEs being mild to moderate in intensity and resolved by the end of 
the study. 
Refer to the Investigator’s Brochure (IB) for detailed background information on MK-8527. 
2.2 
Rationale 
2.2.1 Rationale for this Study and Study Design 
There are large numbers of people using PrEP worldwide and it is expected that a substantial 
number of these individuals accumulate co-morbidities, including chronic medical conditions 
such as diabetes and hypertension that can lead to renal insufficiency. Preclinical and clinical 
studies indicate that renal excretion plays a prominent role in the elimination of MK-8527, 
with the balance eliminated primarily through glucuronidation. In MK-8527-001 and 
MK-8527-003 studies, urine samples were collected for PK assessment after single or 
multiple weekly doses of MK-8527. Urine fe (fraction excreted) in these studies ranged from 
28% to 38%. As such, this study is being conducted to assess the impact of moderate and 
severe RI on the PK of MK-8527 and MK-8527-TP. 
The PK study design selected for this study is in accordance with Food and Drug 
Administration (FDA) recommendations for PK studies in participants with impaired renal 
function (FDA, 2020). Healthy matched control participants with normal renal function will 
be enrolled in the study as controls to detect any clinically relevant PK differences between 
healthy control participants with normal renal function and participants with moderate and 
severe RI. Healthy participants will be matched to the combined mean age, mean BMI, and 
sex of participants with moderate and severe RI. In addition, at least 1 participant of each sex 
will be enrolled in each group (i.e., moderate RI, severe RI, and healthy control). 
2.2.2 Rationale for the Dose Selection 
The single dose of 6 mg MK-8527 selected for this study is expected to be safe and well 
tolerated for participants. Multiple doses of 6 mg MK-8527 given monthly are being studied 
in an ongoing Phase 2 study (MK-8527-007). PK of MK-8527 and MK-8527-TP is 
dose-proportional across doses ranging up to 100 mg and thus increases up to 2-fold in 
renally impaired participants would not be expected to exceed the exposures at the 12 mg top 
dose in the MK-8527-007 study. 
2.2.3 Rationale for Endpoints 
Plasma MK-8527 PK (AUC0-last, AUC0-inf, Cmax, Tmax, t½, CL/F, and Vz/F) is the 
primary endpoint as MK-8527 is renally excreted and will be the primary PK parameter that 
will be monitored in Phase 3 studies. Intracellular MK-8527-TP PK will be a secondary 
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endpoint as it is important to evaluate the impact of RI on the active metabolite MK-8527-TP 
levels. 
2.3 
Risks and/or Benefits to Participants 
The dose of MK-8527 administered in this study is not expected to induce any potential risk 
to participants in this study, as it was generally well-tolerated in prior clinical studies. 
Dose-dependent decreases in total lymphocyte and lymphocyte subset counts were observed 
in clinical studies with islatravir (MK-8591), another investigational nucleoside reverse 
transcriptase inhibitor agent, in development for HIV treatment by the Sponsor. 
 
 It is 
expected that the risk of lymphocyte reductions is low at the levels of MK-8527-TP obtained 
following a 6 mg single dose of MK-8527, based on available nonclinical and clinical data. 
In the MK-8527 clinical studies to date, there have been no AEs associated with lymphocyte 
reductions, and mean lymphocyte counts were unchanged in both single and multiple 
ascending dose studies. As precautionary safety measures, however, lymphocyte parameters 
(e.g., total lymphocytes counts, CD4+ T cell counts) will be monitored in this study for any 
potential reductions. 
The safety monitoring practices employed by this protocol (i.e., AEs, clinical laboratory 
tests, total lymphocytes and CD4+ T cell counts, vital signs, 12-lead ECG, and physical 
examination) are adequate to protect the participants’ safety and are appropriate for this stage 
of development based on the existing safety and tolerability profile. 
There will be no direct therapeutic benefit for study participants from receipt of study drug, 
as clinical studies are designed to provide information about the safety and properties of an 
investigational medicine. A potential indirect health benefit to the participants enrolled in this 
study is the free medical tests received at screening and during the study. 
 
 
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3 
STUDY OBJECTIVES AND ENDPOINTS 
Objectives 
Endpoints 
Primary 
• To evaluate the plasma PK of MK-8527 
in participants with moderate and severe 
RI compared to healthy matched control 
participants. 
Estimation: In participants with 
moderate and severe RI, plasma PK 
(e.g., AUC0-inf, Cmax) of MK-8527 
following a single 6 mg dose of 
MK-8527 will be estimated and 
compared to those observed in healthy 
matched control participants. 
• AUC0-last, AUC0-inf, Cmax, Tmax, 
t½, CL/F, and Vz/F for MK-8527 in 
plasma. 
Secondary 
• To evaluate the safety and tolerability of 
MK-8527 in participants with moderate 
and severe RI. 
• AEs and discontinuations due to AEs. 
• To evaluate the intracellular PK of 
MK-8527-TP in PBMCs in participants 
with moderate and severe RI compared 
to healthy matched control participants. 
Estimation: In participants with 
moderate and severe RI, intracellular PK 
(e.g., AUC0-inf, Cmax) of MK-8527-TP 
in PBMCs following a single 6 mg dose 
of MK-8527 will be estimated and 
compared to those observed in healthy 
matched control participants. 
• AUC0-last, AUC0-inf, Cmax, C168, 
C672, Tmax, and t½ for MK-8527-TP 
in PBMCs. 
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Objectives 
Endpoints 
Exploratory 
• To explore the relationship between 
genetic variation and response to the 
treatment(s) administered, and 
mechanisms of disease. Variation across 
the human genome may be analyzed for 
association with clinical data collected in 
the study. 
• Germline genetic variation and 
association to clinical data collected in 
this study. 
• To evaluate urinary excretion of intact 
MK-8527 in participants with moderate 
and severe RI compared to healthy 
matched control participants. 
• Ae, CLr, and fe for MK-8527 in urine. 
 
 
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4 
STUDY DESIGN 
4.1 
Description of Study Design 
This is a multi-site, open-label, single-dose study to evaluate the effect of moderate and 
severe RI on the PK, safety, and tolerability of MK-8527. 
A total of approximately 18 adult male and female participants will be enrolled, with 
6 participants with moderate RI, 6 participants with severe RI, and 6 healthy matched control 
participants. Healthy control participants will be enrolled after all moderate and severe RI 
participants have been dosed and will be matched by the mean age (± 15 years), mean BMI 
(± 3.5 kg/m2), and sex (± 2) of participants with moderate and severe RI. At least 1 
participant of each sex will be enrolled in each group. 
Screening of participants will occur within 28 days prior to dosing. 
Participants will receive a single oral dose of MK-8527 on Day 1. PK sampling will be 
performed predose and up to 168 hours postdose for plasma MK-8527 and predose and up to 
672 hours postdose for PBMC MK-8527-TP. Urine will be collected predose and up to 
48 hours postdose for MK-8527 PK. 
Safety will be monitored throughout the study by repeated clinical and laboratory 
evaluations. 
Discontinued participants may be replaced at the discretion of the Sponsor. 
4.1.1 Confinement, Return Visits, and Follow-Up 
Participants will be housed on Day -1, at the time indicated by the CRU, until completion of 
study procedures on Day 8. Participants will return for study procedures as indicated in the 
Schedule of Activities (Section 1.3). 
As per site preference, participants may be confined longer at the discretion of the Principal 
Investigator (PI) or designee, and/or confined for additional short periods throughout the 
study (e.g., to facilitate attendance at return visits). 
All participants who received the study drug (including participants who terminate the study 
early) will return to the CRU on Day 29 (±1 day) for follow-up procedures and to determine 
if any AE has occurred since the last study visit. 
4.1.2 Study Duration 
The total planned study duration (from screening to follow-up) for each participant is 
approximately 8 weeks. 
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4.2 
Beginning and End of Study 
The overall study begins when the first participant provides documented informed consent. 
The overall study ends when the last participant completes the last study-related contact, 
withdraws consent, or is lost to follow-up. 
The end of study is defined as the date of the last scheduled procedure. If there is an 
unresolved AE, end date of concomitant medication, or an assessment date that is after the 
end of study, the date of study completion will be inclusive of that resolution/assessment 
date. 
A participant is considered to have completed the study if the participant completed dosing, 
did not terminate the study early, and has completed the last scheduled procedure i.e., the 
follow-up visit shown in the Schedule of Activities (Section 1.3). 
The study may be paused during review of newly available preclinical/clinical safety, PK, 
pharmacodynamic, efficacy, or biologic data or other items of interest, prior to a final 
decision on continuation or termination of the study. It may be necessary to keep the study 
open for gathering/reviewing of additional supportive data to optimally complete the 
objective(s) of the study. If necessary, the appropriate amendment(s) to the protocol and/or 
appropriate communication(s) will be generated. If the decision has been made to end the 
study following this review period, the study end will be defined as the date of the Sponsor 
decision, and this end of study date supersedes the definitions outlined above. The 
Competent Authority(ies) and institutional review board(s) (IRB[s]) will be apprised of the 
maximum duration of the study beyond the last participant out and the justification for 
keeping the study open. 
4.2.1 Clinical Criteria for Early Study Termination 
There are no prespecified criteria for terminating the study early. 
4.3 
Study Design/Dosing/Procedures Modifications Permitted Within Protocol 
Parameter 
This is a Phase 1 assessment of MK-8527 in humans, and the PK, pharmacodynamic, and 
safety profiles of the compound are still being elucidated. This protocol is written with some 
flexibility to accommodate the inherent dynamic nature of Phase 1 clinical studies. 
Modifications to the dose and/or clinical or laboratory procedures currently outlined may be 
required to achieve the scientific goals of the study objectives and/or to ensure appropriate 
safety monitoring of the study participants. 
As such, some alterations from the currently outlined design may be permitted based on 
newly available data: 
• Alteration of the dose, but it cannot exceed the one currently outlined in the protocol 
• Addition of PK pause 
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• Instructions to take study drug with or without food or drink may also be modified based 
on newly available data 
• Modification of the PK/pharmacodynamic sample processing and shipping details based 
on newly available data 
• Modification of urine sample collection 
The PK/pharmacodynamic sampling scheme currently outlined in the protocol may be 
modified during the study based on newly available PK/pharmacodynamic data (e.g., to 
obtain data closer to the time of peak plasma concentrations). If indicated, these collected 
samples may also be assayed in an exploratory manner for metabolites and/or additional 
pharmacodynamic markers. 
The total blood volume withdrawn from any single participant will not exceed the maximum 
allowable volume during his/her participation in the entire study (Table 3). 
The timing of procedures for assessment of safety procedures (e.g., vital signs, ECG, safety 
laboratory tests, total lymphocytes and CD4+ T cell counts, etc.) may be modified during the 
study based on newly available data. Additional laboratory safety tests may be added to 
blood samples previously drawn to obtain additional safety information. These changes will 
not increase the number of study procedures for a given participant during his/her 
participation in the entire study. 
It is understood that the current study may use some or none of the alterations described 
above. Any alteration made to this protocol to meet the study objectives must be detailed by 
the Sponsor in a letter to the Study File and forwarded to the PI for retention. The letter may 
be forwarded to the IRB at the discretion of the PI. 
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5 
STUDY POPULATION 
Prospective approval of protocol deviations to recruitment and enrollment criteria, also 
known as protocol waivers or exemptions, is not permitted. 
5.1 
Inclusion Criteria 
Participants must fulfill all of the following inclusion criteria to be eligible for participation 
in the study: 
All Participants: 
1. The participant is an adult, male or female, 18 to 75 years of age, inclusive, at screening. 
2. Female and male participants must follow protocol-specified contraception guidance as 
described in Section 5.3.4. 
3. The participant is a continuous non-smoker or moderate smoker (≤ 10 cigarettes per day 
or equivalent) for at least 3 months prior to dosing. Participant must agree to maintain the 
same smoking status (i.e., smoker or non-smoker) from screening and until after the last 
PK sample collection. Smokers must agree to smoke no more than 5 cigarettes (or 
equivalent) per day from check-in until after the last PK sample collection. 
4. The participant has a BMI ≥ 18.0 and ≤ 40.0 kg/m2 at screening. 
5. The participant understands the study procedures in the informed consent form (ICF), and 
is willing and able to comply with the protocol. 
6. The participant has provided documented informed consent for the study. The participant 
may also provide consent for Future Biomedical Research (FBR). However, the 
participant may participate in the study without participating in FBR. 
Participants with Moderate and Severe RI (Groups 1 and 2): 
7. With the exception of RI, the participant is sufficiently healthy for study participation 
based on medical history, physical examination, vital signs, and ECGs, as deemed by the 
PI or designee, including the following: 
• Heart rate is ≥ 40 bpm and ≤ 110 bpm at screening. 
• QTcF interval is ≤ 500 msec and has ECG findings considered normal or not 
clinically significant by the PI or designee at screening. 
Participants with stable, chronic medical or psychiatric conditions, including but not 
limited to hypertension, cardiac disease, hypercholesterolemia, non-insulin dependent 
diabetes mellitus, hyper- or hypothyroidism, gout, and chronic anxiety or depression may 
be included at the discretion of the PI or designee and the Sponsor. 
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8. With the exception of RI, the participant is sufficiently healthy for study participation 
based on clinical laboratory profiles at screening and check-in. 
9. The participant has impaired renal function as determined by estimated glomerular 
filtration rate (eGFR) using the 2021 Chronic Kidney Disease Epidemiology 
Collaboration (CKD-EPI) creatinine equation at screening, as follows: 
• Group 1 (moderate RI): eGFR 30 to 59 mL/min, inclusive. 
• Group 2 (severe RI): eGFR 15 to 29 mL/min, inclusive. 
The baseline eGFR will be obtained by taking the mean of two eGFR values obtained 
≥ 72 hours apart during screening. The second baseline eGFR sample may be obtained at 
the time of check-in. 
2021 CKD-EPI Creatinine Equation: 
eGFR = 142 X min(Scr/k,1)α X max(Scr/k,1)-1.200 X 0.994age  X 1.012 [if female] 
where Scr is serum creatinine, k is 0.7 for females and 0.9 males, α is -0.241 for 
females and -0.302 for males, min indicates the minimum of Scr/k or 1, max indicates 
the maximum of Scr/k or 1. 
The eGFR for eligibility will use de-indexed values to correct for participant’s body 
surface area (BSA). To convert indexed eGFR expressed as mL/min/1.73 m2, the indexed 
eGFR value will be multiplied by participant’s BSA and this value will be divided by 
1.73 and expressed as mL/min. The DuBois formula will be used to calculate BSA: 
BSA (m2) = Weight (kg)0.425 x Height (cm)0.725 x 0.007184 
10. The participant has stable renal function as determined by historical measurements. 
Stable renal function is defined as ≤ 30% difference between two measurements of eGFR 
taken ≥ 72 hours apart during screening. 
Healthy Control Participants (Group 3): 
11. The participant must match the mean age (± 15 years) of participants with moderate and 
severe RI (Groups 1 and 2). 
12. The participant must match the mean BMI (± 3.5 kg/m2) of participants with moderate 
and severe RI (Groups 1 and 2). 
13. The participant is medically healthy with no clinically significant medical history, 
physical examination, vital signs, and ECGs, as deemed by the PI or designee, at 
screening. 
14. The participant is medically healthy with no clinically significant clinical laboratory 
profiles, as deemed by the PI or designee, at screening and check-in. 
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15. The participant has normal renal function with eGFR ≥ 90 mL/min, determined using the 
2021 CKD-EPI creatinine equation at screening. Healthy participants who have an eGFR 
of 80 to 89 mL/min may be enrolled in the study at the discretion of the PI or designee.  
The baseline eGFR will be obtained by taking the mean of two eGFR values obtained 
≥ 72 hours apart during screening. The second baseline eGFR sample may be obtained at 
the time of check-in. 
The eGFR for eligibility will use de-indexed values to correct for participant’s BSA. To 
convert indexed eGFR expressed as mL/min/1.73 m2, the indexed eGFR value will be 
multiplied by participant’s BSA and this value will be divided by 1.73 and expressed as 
mL/min. The DuBois formula will be used to calculate BSA: 
BSA (m2) = Weight (kg)0.425 x Height (cm)0.725 x 0.007184 
5.2 
Exclusion Criteria 
Participants must not be enrolled in the study if they meet any of the following criteria: 
All Participants: 
1. The participant is mentally or legally incapacitated or has significant emotional problems 
at the time of screening or expected during the conduct of the study. 
2. The participant has a history or presence of alcohol or drug abuse (except for cannabis) 
within the past 2 years prior to dosing. 
3. The participant has a history or presence of hypersensitivity or idiosyncratic reaction to 
the study drug or related compounds. 
4. The participant has a history of cancer (malignancy). Participants with adequately treated 
disease deemed as “cured,” or who, in the opinion of the PI or designee, are highly 
unlikely to sustain a recurrence for the duration of the study may be enrolled at the 
discretion of the PI or designee. 
5. The participant is a female participant with a positive pregnancy test at screening or at 
check-in or who is lactating. 
6. The participant has a positive drug result at screening or check-in, unless the positive 
drug screen is due to prescription drug use that is approved by the PI or designee and 
Sponsor. 
7. The participant has a positive alcohol result at screening or check-in. 
8. The participant consumes greater than 3 servings of alcoholic beverages (1 serving is 
approximately equivalent to: beer [354 mL/12 oz], wine [118 mL/4 oz], or distilled spirits 
[29.5 mL/1 oz]) per day. Participants who consume 4 servings of alcoholic beverages per 
day may be enrolled at the discretion of the PI or designee. 
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9. The participant consumes excessive amounts, defined as greater than 6 servings 
(1 serving is approximately equivalent to 120 mg of caffeine), of coffee, tea, cola, energy 
drinks, or other caffeinated beverages per day. 
10. The participant has positive results for HIV, hepatitis B surface antigen (HBsAg), or 
hepatitis C virus (HCV) at screening. 
11. The participant has a positive coronavirus disease 2019 (COVID-19) result at check-in. 
12. The participant is unable to refrain from or anticipates the use of any drugs (except for 
permitted medication as detailed in Section 6.7), including prescription and 
non-prescription medications, herbal remedies, or vitamin supplements, as indicated in 
Section 6.7. 
13. The participant has been on a diet incompatible with the on-study diet, in the opinion of 
the PI or designee, within the 30 days prior to dosing. 
14. The participant has had major surgery and/or donated or lost significant volume of blood 
within 56 days prior to dosing. 
15. The participant has donated plasma within 7 days prior to dosing. 
16. The participant has been in another clinical study within 30 days or within 5 half-lives (if 
known), prior to dosing, whichever is longer. The 30-day window will be derived from 
the date of the last blood collection or dosing, whichever is later, in the previous study to 
Day 1 of the current study. 
17. The participant is or has an immediate family member (e.g., spouse, parent/legal 
guardian, sibling, or child) who is CRU or Sponsor staff directly involved with this study. 
Participants with Moderate and Severe RI (Groups 1 and 2): 
18. With the exception of RI, the participant has a history or presence of clinically significant 
medical or psychiatric condition or disease, any illness that, in the opinion of the PI or 
designee, might confound the results of the study or poses an additional risk to the 
participant by their participation in the study. 
19. The participant has had a failed renal transplant or has had a nephrectomy. 
20. The participant has end stage renal disease requiring dialysis. 
21. The participant has any significant arrhythmia or conduction abnormality (including but 
not specific to atrioventricular block [second degree or higher], Wolff-Parkinson-White 
syndrome [unless curative radio ablation therapy]), which, in the opinion of the PI and 
Sponsor, could interfere with the safety for the individual participant. 
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22. The participant has non-sustained or sustained ventricular tachycardia (> 2 consecutive 
ventricular ectopic beats at a rate of > 1.7/second). 
Healthy Control Participants (Group 3): 
23. The participant has a history or presence of clinically significant medical or psychiatric 
condition or disease, or any illness that, in the opinion of the PI or designee, might 
confound the results of the study or poses an additional risk to the participant by their 
participation in the study. 
5.3 
Lifestyle Considerations 
5.3.1 Meals and Dietary Restrictions 
5.3.1.1 Meals 
Water (except water provided with dosing) will be restricted 1 hour prior to and 1 hour after 
dosing, but will be allowed ad libitum at all other times. Other fluids may be given as part of 
meals and snacks but will be restricted at all other times throughout the confinement period. 
Participants will be required to fast overnight for at least 10 hours prior to dosing and will 
continue to fast for at least 4 hours postdose. 
Each meal and/or snacks served at the CRU will be standardized and of similar caloric 
content and composition and will be taken at approximately the same time on each day. 
When confined, standard meals and snacks will be provided at appropriate times, except 
when participants are required to fast. When confined in the CRU, participants will be 
required to fast from all food and drink except water between meals and snacks. 
5.3.1.2 Dietary Restrictions 
The consumption of foods and beverages containing grapefruit and/or Seville orange will be 
prohibited from 14 days prior to dosing and until completion of study procedures on Day 8. 
5.3.2 Caffeine, Alcohol, and Tobacco Restrictions 
Participants will refrain to use the following: 
• Xanthines/Caffeine-containing foods or beverages: 24 hours prior to dosing and until 
completion of study procedures on Day 8 (small amounts of caffeine derived from 
normal foodstuffs e.g., 250 mL/8 oz/1 cup decaffeinated coffee or other decaffeinated 
beverage, per day, with the exception of espresso; 45 g/1.5 oz chocolate bar, per day, 
would not be considered a deviation to this restriction). 
• Alcohol-containing foods or beverages: 48 hours prior to dosing and until completion of 
study procedures on Day 8, and 24 hours prior to each subsequent visit on Days 15 (±1 
day), 22 (±1 day), and 29 (±1 day). 
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• Tobacco/nicotine containing products: Participant must agree to maintain the same 
smoking status (i.e., smoker or non-smoker) from screening and until after the last PK 
sample collection. Depending on the CRU rules and regulations, participants may be 
prohibited from smoking during their confinement or during portions of their 
confinement. 
5.3.3 Activity Restrictions 
Participants will remain ambulatory or seated upright for the first 4 hours postdose, except 
when they are supine or semi-reclined for study procedures. 
Should AEs occur at any time, participants may be placed in an appropriate position or will 
be permitted to lie down on their right side. 
Specific measures will be taken to prevent the participant from missing a urine collection by 
strictly controlling and providing access to designated restrooms only. Participants will be 
asked to void prior to entering the shower. 
Participants will be instructed to refrain from strenuous physical activity which could cause 
muscle aches or injury, including contact sports at any time from screening until the last 
blood sample collection. 
Participants will be cautioned against activities requiring mental alertness, judgment and 
physical coordination such as driving, operating machinery, or power equipment for a period 
of 24 hours postdose. 
5.3.4 Contraception Requirements 
5.3.4.1 
Definitions 
Females of childbearing potential are defined as all females physiologically capable of 
becoming pregnant.  
Females of non-childbearing potential are defined as follows: 
• Females who have undergone one of the following sterilization procedures at least 
6 months prior to dosing/the dosing administered to the male partner: 
o Hysteroscopic sterilization. 
o Bilateral tubal ligation or bilateral salpingectomy. 
o Hysterectomy. 
o Bilateral oophorectomy 
or 
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• Females who are postmenopausal with amenorrhea for at least 1 year prior to the 
dosing/the dosing administered to the male partner and have follicle-stimulating hormone 
(FSH) serum levels consistent with postmenopausal status at screening. 
5.3.4.2 Guidance for Female Participants 
Female participants of non-childbearing potential are not required to use any contraception 
methods. 
Female participants of childbearing potential must agree to one of the following methods of 
contraception: 
• Sexually inactive for at least 28 days prior to dosing. 
• Non-hormonal releasing intrauterine device (IUD) or hormonal contraceptives 
(e.g., oral, IUD, vaginal ring, transdermal patch, depot, implantable, etc.) for at least 
3 months prior to dosing. 
• Surgical sterilization of the partner (vasectomy for 4 months minimum prior to dosing). 
• Physical barrier method (e.g., condom, diaphragm) with spermicide for at least 14 days 
prior to dosing. 
A female participant who claims to be sexually inactive, but becomes sexually active during 
the course of the study must agree to use a physical barrier method (e.g., condom, 
diaphragm) with spermicide from the time of the start of sexual activity and until at least 
28 days after dosing. 
In addition, female participants of childbearing potential will be advised to remain sexually 
inactive or to keep the same birth control method for at least 28 days after dosing. 
Female participant must agree not to donate ova from dosing until at least 28 days after 
dosing. 
5.3.4.3 Guidance for Male Participants 
If capable of producing sperm, the male participant must agree to the following from dosing 
until at least 28 days after dosing of study drug: 
• Refrains from donating sperm. 
PLUS either: 
• Abstains from penile-vaginal intercourse as their preferred and usual lifestyle (abstinent 
on a long-term and persistent basis) and agrees to remain abstinent. 
OR 
• Uses contraception as detailed below unless confirmed to be azoospermic (vasectomized 
for at least 4 months prior to dosing or secondary to medical cause, documented from the 
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site personnel’s review of the participant’s medical records, medical examination, or 
medical history interview) as detailed below: 
o Uses a penile/external condom when having penile-vaginal intercourse with a female 
partner of childbearing potential who is not currently pregnant and should also be 
advised of the benefit for that partner to use an additional method of contraception, as 
a condom may break or leak. 
Note: Participants capable of producing ejaculate whose partner is pregnant or 
breastfeeding must agree to use a penile/external condom during each episode of 
sexual activity in which the partner is at risk of drug exposure via ejaculate. 
o Contraceptive use by participants capable of producing sperm should be consistent 
with local regulations regarding the methods of contraception for those participating 
in clinical studies. If the contraception requirements in the local label for any of the 
study drugs are more stringent than the requirements above, the local label 
requirements are to be followed. 
 
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6 
STUDY TREATMENTS AND CONCOMITANT THERAPY 
6.1 
Description of Study Treatments 
The study drug to be used in this study is outlined in Table 1. 
Study drug assignments are described in Section 6.3.1. 
Table 1: Study Drugs 
Group Name 
Treatment 
Type 
Study Drug 
Name 
Study 
Drug 
Type 
Dose 
Formulation 
Unit Dose 
Strength(s) 
Dosage 
Level(s) 
Route of 
Administration 
Regimen/ 
Treatment 
Period 
Use 
IMP/ 
NIMP/ 
AxMP 
Sourcing 
Moderate RI 
(Group 1) 
Experimental 
MK-8527 
Drug 
Capsule 
1 mg 
5 mg 
6 mg 
Oral 
Single dose, 
Day 1 
Test 
product 
IMP 
Sponsor 
Severe RI 
(Group 2) 
Healthy Control 
(Group 3) 
Abbreviations: IMP = investigational medicinal product, NIMP/AxMP = non-investigational/auxiliary medicinal product. 
The study drug will be administered orally with approximately 240 mL of water. 
Participants will be instructed not to crush, split, or chew the study drug. 
The pharmacy at the CRU will provide the dose in individual unit dose containers for each participant. 
The exact clock time of dosing will be recorded. 
 
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6.2 
Drug Supplies, Storage, and Accountability 
The Sponsor will supply sufficient quantities of MK-8527 to allow completion of this study. 
The lot numbers and expiration dates (where available) of the study drugs supplied will be 
recorded in the clinical study report (CSR). 
All study drugs must be stored in a secure, temperature controlled, and monitored area in 
accordance with the study drugs storage requirements, with access limited to the PI and 
designated CRU personnel. 
Records will be made of the receipt and dispensing of the study drugs supplied. At the 
conclusion of the study, any unused study drug will be retained by Celerion, returned to the 
Sponsor or designee, or destroyed, as per Sponsor instructions. 
6.3 
Study Dose Modification 
Refer to Section 4.3. 
6.3.1 Stopping Rules 
The following stopping rules will be used during the conduct of this study. 
If any of the below stopping rules are met, the study will be paused, and no further dosing 
will occur until the Sponsor has reviewed the totality of data available. To continue the study 
(on joint agreement with the Sponsor and PI), a substantial amendment will be submitted for 
approval. 
1. An individual participant reports an SAE considered related to the study drug by the PI. 
2. Two (2) or more participants report Severe Nonserious AEs considered related to the 
study drug by the PI. 
6.4 
Participant Assignment and Randomization 
All participants will receive a single oral dose of 6 mg MK-8527 (1 x 1 mg capsule + 
1 x 5 mg capsule) on Day 1. 
Each participant will be assigned a unique identification number upon screening. Participants 
who complete the study screening assessments and meet all the eligibility criteria will be 
assigned a unique identification number, different from the screening number, and will 
receive the study drug. 
No randomization will be performed in this study. All participants will receive the study 
drug. 
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6.4.1 Participant Identification Card 
Prior to first discharge from the CRU, participants who received any portion of study drug 
will be given a participant identification card identifying them as participants in a research 
study. The card will contain the identification number and CRU contact information 
(including direct telephone numbers) to be used in the event of an emergency. 
6.5 
Blinding 
This is an open-label study. 
6.6 
Study Treatment Compliance 
A qualified designee will be responsible for monitoring the administration of the timed oral 
dose. Once a participant has finished the dosing water, the qualified designee will use a 
flashlight and a tongue depressor to check the participant’s mouth to ensure that the 
participant has swallowed the study drug. Participants’ hands will also be verified to ensure 
that the study drug was ingested. 
6.7 
Concomitant Therapy 
Participants with Moderate and Severe RI (Groups 1 and 2): 
In general, the use of any concomitant medication/therapy required to treat the current 
disease of a participant may be permitted following consultation with the Sponsor (except 
when specifically prohibited). 
Participants who are taking medications to treat manifestations of renal disease or 
medications needed to treat stable diseases (e.g., angiotensin converting enzyme inhibitors, 
angiotensin II receptor antagonists, beta-blockers, diuretics, metformin, insulin, 
thiazolidinediones, sulfonylureas, dipeptidyl peptidase-4 inhibitors, alpha-glucosidase 
inhibitors, sodium-glucose cotransporter 2 inhibitors, statins) that are common in patients 
with RI will be allowed to participate in the study at the discretion of the PI or designee and 
following consultation with the Sponsor. Participants must be on a stable dose (steady dose, 
drug, and regimen) for at least 14 days before MK-8527 dosing (at least 28 days prior to 
MK-8527 dosing for diuretic treatment, and at least 3 months prior to MK-8527 dosing for 
thyroid hormone replacement medication) and able to withhold the use of their maintenance 
medication until at least 4 hours after MK-8527 dosing. 
Phosphate binders containing aluminum, calcium, or lanthanum salts; iron supplements or 
other metal cations; H2-receptor antagonists (except cimetidine); or multivitamins containing 
iron or zinc must be withheld at least 8 hours before MK-8527 dosing and at least 4 hours 
postdose. Any medication (including over-the-counter) that would significantly alter eGFR, 
which, by the determination of the PI or designee, might interfere with the study 
(e.g., cimetidine) must be discontinued at least 2 weeks prior to MK-8527 dosing and 
throughout the study. 
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Changes to medication that require frequent dose adjustments, such as insulin, furosemide 
(Lasix), spironolactone (Aldactone), or analgesic, may be made at least 14 days prior to 
MK-8527 dosing and may be considered if medically necessary thereafter, at the discretion 
of the PI and following consultation with the Sponsor. 
If a participant is prescribed prohibited medication, upon discussion between the Sponsor and 
the PI, the PI may substitute the previously prescribed medication to an allowed one for the 
purpose of this study. 
Healthy Control Participants (Group 3): 
Any drugs, including prescription and non-prescription medications (with the exception of 
oral contraception, hormone replacement therapy, and thyroid hormone replacement 
medication), vitamins, or herbal and dietary supplements, are prohibited beginning 14 days 
prior to MK-8527 dosing and until after the last PK sample collection. However, healthy 
participants who are on stable medication for at least 30 days prior to MK-8527 dosing may 
be enrolled upon approval by the PI or designee and the Sponsor. 
Certain medications may be deemed acceptable at the discretion of the PI and following 
consultation with the Sponsor, but participants must be on a stable regimen for at least 
28 days prior to MK-8527 dosing. If a participant is prescribed prohibited medication, upon 
discussion between the Sponsor and the PI, the PI may substitute the previously prescribed 
medication to an allowed one for the purpose of this study. 
All Participants: 
Birth control methods are allowed as described in Section 5.3.4.2. 
Hormone replacement therapy and thyroid hormone replacement medication will be allowed, 
if the participant has been on the same stable dose for at least 3 months prior to dosing. 
After dosing, acetaminophen (up to 2 g per 24-hour period) may be administered at the 
discretion of the PI or designee. Administration of other concomitant medication will be 
permitted for the treatment of AEs, only when deemed necessary and when agreed by the PI 
and Sponsor, unless appropriate medical care necessitates that therapy should begin before 
the PI and Sponsor can be consulted. 
COVID-19 and flu vaccines may be allowed if administered at least 72 hours before dosing 
or at least 48 hours after dosing. 
If deviations occur, the PI or designee in consultation with the Sponsor, if needed, will decide 
on a case-by-case basis whether the participant may continue participation in the study. 
All medications taken by participants beginning 2 weeks prior to screening and during the 
course of the study will be recorded. 
 
 
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7 
DISCONTINUATION OF STUDY DRUG AND PARTICIPANT WITHDRAWAL 
7.1 
Discontinuation of Study Drug 
Not applicable. 
7.2 
Participant Withdrawal from the Study 
Participants are free to withdraw from the study at any time for any reason. If a participant 
withdraws from the study, they will no longer receive study drug or be followed at scheduled 
protocol visits. 
In addition, participants may be withdrawn from the study by the PI or designee or the 
Sponsor for the following reasons but not limited to: 
• AEs. 
• Pregnancy. 
• Difficulties in blood collection. 
• Positive drug or alcohol test. 
• Enrollment into the study is inappropriate. 
• Non-compliance. 
• Protocol violation. 
• Study terminated by Sponsor. 
The PI or designee must notify the Sponsor when a participant has discontinued or 
withdrawn from the study. If a participant discontinues or withdraws prior to study 
completion, efforts should be made to perform all procedures scheduled for early termination 
as outlined in the Schedule of Activities (Section 1.3), as well as specific details regarding 
withdrawal from FBR, are outlined in Section 7.2.1. 
7.2.1 Withdrawal From Future Biomedical Research 
Participants may withdraw their consent for FBR. Participants may withdraw consent at any 
time by contacting the PI or designee. If medical records for the study are still available, the 
PI or designee will contact the Sponsor using the designated mailbox 
(clinical.specimen.management@MSD.com). Subsequently, the participant’s consent for 
FBR will be withdrawn. A letter will be sent from the Sponsor to the PI confirming the 
withdrawal. It is the responsibility of the PI or designee to inform the participant of 
completion of withdrawal. Any analyses in progress at the time of request for withdrawal or 
already performed before the request being received by the Sponsor will continue to be used 
as part of the overall research study data and results. No new analyses would be generated 
after the request is received. 
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If the medical records for the study are no longer available (e.g., if the PI is no longer 
required by regulatory authorities to retain the study records) or the specimens have been 
completely anonymized, there will no longer be a link between the participant’s personal 
information and their specimens. In this situation, the request for specimen withdrawal 
cannot be processed. 
7.3 
Lost to Follow-up 
If a participant fails to return to the CRU for a required study visit and/or if the CRU is 
unable to contact the participant, the following procedures are to be performed: 
• The CRU must attempt to contact the participant and reschedule the missed visit. If the 
participant is contacted, the participant should be counseled on the importance of 
maintaining the protocol-specified visit schedule. 
• The PI or designee must make every effort to regain contact with the participant at each 
missed visit (e.g., telephone calls and/or a certified letter to the participant’s last known 
mailing address or locally equivalent methods). These contact attempts should be 
documented in the participant’s medical record. 
• Note: A participant is not considered lost to follow-up until the last scheduled visit for the 
individual participant. The missing data for the participant will be managed via the 
prespecified statistical data handling and analysis guidelines. 
 
 
 
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8 
STUDY ASSESSMENTS AND PROCEDURES 
The Schedule of Activities (Section 1.3) summarizes the clinical procedures to be performed 
at each visit. Individual clinical procedures will be carried out as per CRU standard operating 
procedures and are described briefly below. Additional evaluations/testing may be deemed 
necessary by the PI or designee and/or the Sponsor for reasons related to participant safety. 
For this study, the blood collection for MK-8527 is the critical parameter and needs to be 
collected as close to the exact time point as possible. All other procedures should be 
completed as close to the prescribed/scheduled time as possible, but can be performed prior 
or after the prescribed/scheduled time.  
Any nonscheduled procedures required for urgent evaluation of safety concerns take 
precedence over all routine scheduled procedures. 
8.1 
Screening Assessments and Procedures 
Within 28 days prior to dosing, medical history and demographic data, including name, sex, 
age, race, ethnicity, body weight (kg), height (cm), BMI (kg/m2), and history of tobacco use 
(including number of cigarettes smoked per day) will be recorded. At screening, each 
participant will be assessed by collection of clinical laboratory tests, vital sign measurements 
(heart rate, blood pressure, temperature, and respiratory rate), 12-lead ECG, and a physical 
examination. 
Participants who do not qualify based on a reversible condition or mild intercurrent illness 
may be re-evaluated after further testing/examination or re-screened after the condition is 
resolved. Screening tests may be repeated per the PI’s discretion and upon approval of the 
Sponsor. In the event that participation of a participant in the study is delayed and some or all 
screening procedures had been performed outside the prescribed screening window, outdated 
screening procedures will be repeated. Inclusion and categorization laboratory assessments 
that are deemed inconsistent with the usual stage of RI may be repeated at the discretion of 
the PI. 
For eligibility purposes, abnormal laboratory test results may be repeated at the discretion of 
the PI if an abnormal result is observed at the initial reading. 
8.1.1 Screen Failures 
Screen failures are defined as participants who consent to participate in the clinical study but 
are not subsequently entered in the study. The data from participants who fail at screening 
will not be reported in the case report forms (CRFs). 
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8.2 
Safety Assessments and Procedures 
8.2.1 Physical Examination 
A full physical examination will be performed as outlined in the Schedule of Activities 
(Section 1.3). Additional physical examinations may be performed at other times, if deemed 
necessary by the PI or designee.  
8.2.2 Vital Signs 
Single measurements of body temperature, respiratory rate, blood pressure, and heart rate 
will be measured as outlined in the Schedule of Activities (Section 1.3). Additional vital 
signs may be taken at any other times, if deemed necessary by the PI or designee. 
Blood pressure and heart rate measurements will be performed with participants in a seated 
position for 5 minutes, except when they are supine or semi-reclined because of study 
procedures and/or AEs (e.g. nausea, dizziness) or if deemed necessary by the PI or designee. 
The same method must be used for all body temperature measurements for each individual 
participant and should be the same for all participants. 
Vital signs will be measured within 3 hours prior to Day 1 dosing. When scheduled postdose, 
vital signs will be performed within ± 2 hours (for ≤ 168 hours postdose) and within ± 1 day 
(for > 168 hours and ≤ 672 hours postdose) of the scheduled time point. 
8.2.3 Electrocardiograms 
Single 12-lead ECGs will be performed will be performed within an approximately 5-minute 
time window as outlined in the Schedule of Activities (Section 1.3). Additional ECGs may be 
taken at any other times, if deemed necessary by the PI or designee. 
ECGs will be performed with participants in a supine position for 5 minutes. All ECG 
tracings will be reviewed by the PI or designee. 
ECGs will be measured within 3 hours prior to Day 1 dosing. When scheduled postdose, 
ECGs will be performed within ± 2 hours (for ≤ 168 hours postdose) and within ± 1 day (for 
> 168 hours and ≤ 672 hours postdose) of the scheduled time point. 
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8.2.4 Clinical Laboratory Assessments 
All tests listed below will be performed as outlined in the Schedule of Activities 
(Section 1.3). In addition, laboratory safety tests may be performed at various unscheduled 
time points, if deemed necessary by the PI or designee. 
Hematology 
 
Serum Chemistry * 
• 
Hemoglobin 
• 
Hematocrit  
• 
Total and differential leukocyte 
count 
• 
Red blood cell count 
• 
Platelet count 
 
 
• 
Blood urea nitrogen 
• 
Bilirubin (total and direct) 
• 
Alkaline phosphatase 
• 
Aspartate aminotransferase (AST) 
• 
Alanine aminotransferase (ALT) 
• 
Albumin 
• 
Sodium 
• 
Potassium 
• 
Chloride 
• 
Glucose (fasting) 
• 
Creatinine ** 
• 
Creatine phosphokinase 
 
Urinalysis 
 
Additional Tests 
• 
pH 
• 
Specific gravity 
• 
Protein *** 
• 
Glucose 
• 
Ketones 
• 
Bilirubin 
• 
Blood *** 
• 
Nitrite*** 
• 
Urobilinogen 
• 
Leukocyte esterase *** 
 
• 
HIV test 
• 
HBsAg 
• 
HCV 
• 
Urine/saliva drug screen 
 Opiates 
 Opioids 
 Amphetamines 
 Cocaine 
 Barbiturates 
 Benzodiazepines 
• 
Urine/breath alcohol screen 
• 
COVID-19 screen 
• 
Serum/urine pregnancy test (for females only) 
• 
Serum FSH (for postmenopausal females only) 
 
* 
Serum chemistry tests will be performed after at least an 8-hour fast; however, in case of discontinuations or 
rechecks, participants may not have fasted for 8 hours prior to when the serum chemistry sample is taken. 
** At screening, eGFR will be calculated. 
*** If urinalysis is abnormal for protein, blood, nitrite and/or leukocyte esterase, a microscopic examination (for 
red blood cells, white blood cells, bacteria, casts, and epithelial cells) will be performed. 
8.2.5 Immunophenotyping 
For all participants, blood samples for immunophenotyping (total lymphocyte counts and 
CD4+ T cell counts) will be collected at scheduled time points as delineated in the Schedule 
of Activities (Section 1.3). 
Instructions for blood sampling, collection, processing, and sample shipment will be 
provided separately. 
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8.2.6 Adverse Events and Serious Adverse Events 
8.2.6.1 Definition of Adverse Event 
An AE means any untoward medical occurrence associated with the use of a drug in humans, 
whether or not considered drug related. An AE will be considered treatment-emergent if the 
onset date and time is at the time of or after study drug administration. 
A suspected adverse reaction means any AE for which there is a reasonable possibility that 
the drug caused the AE. Reasonable possibility means there is evidence to suggest a causal 
relationship between the drug and the AE.  
An AE can therefore be any unfavorable and unintended sign (including an abnormal 
laboratory finding), symptom, or disease temporally associated with the use of a medicinal 
(investigational) product, whether or not related to the medicinal (investigational) product. 
Note: For purposes of AE definition, study drug includes any pharmaceutical product, 
biological product, vaccine, diagnostic agent, medical device, combination product, or 
protocol-specified procedure whether investigational or marketed (including placebo, active 
comparator product, or run-in treatment), manufactured by, licensed by, provided by, or 
distributed by the Sponsor for human use in this study. 
Events meeting the AE definition 
• Any abnormal laboratory test results (hematology, clinical chemistry, or urinalysis) or 
other safety assessments (e.g., ECG, radiological scans, vital signs measurements), 
including those that worsen from baseline, considered clinically significant in the medical 
and scientific judgment of the PI or designee. 
• Exacerbation of a chronic or intermittent preexisting condition including either an 
increase in frequency and/or intensity of the condition. 
• New conditions detected or diagnosed after study drug administration even though it may 
have been present before the start of the study. 
• Signs, symptoms, or the clinical sequelae of a suspected drug-drug interaction as 
determined by the PI or designee. 
• Signs, symptoms, or the clinical sequelae of a suspected overdose of either study drug or 
a concomitant medication as determined by the PI or designee. 
• For all reports of overdose (whether accidental or intentional) with an associated AE, the 
AE term should reflect the clinical symptoms or abnormal test result. An overdose 
without any associated clinical symptoms or abnormal laboratory results is reported using 
the terminology “accidental or intentional overdose without adverse effect.” 
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Events NOT meeting the AE definition 
• Medical or surgical procedure (e.g., endoscopy, appendectomy): the condition that leads 
to the procedure is the AE. 
• Situations in which an untoward medical occurrence did not occur (social and/or 
convenience admission to a hospital). 
• Anticipated day-to-day fluctuations of preexisting disease(s) or condition(s) present or 
detected at the start of the study that do not worsen. 
• Surgical procedure(s) planned prior to informed consent to treat a preexisting condition 
that has not worsened. 
8.2.6.2 Definition of Serious Adverse Event 
A serious adverse event (SAE) is any AE or suspected adverse reaction that in the view of 
either the PI or designee or Sponsor, results in any of the following outcomes: Death, a 
life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, a 
persistent or significant incapacity or substantial disruption of the ability to conduct normal 
life functions, or a congenital anomaly/birth defect. Important medical events that may not 
result in death, be life-threatening, or require hospitalization may be considered serious 
when, based upon appropriate medical judgment, they may jeopardize the patient or 
participant and may require medical or surgical intervention to prevent one of the outcomes 
listed in the above definition. Examples of such medical events include allergic 
bronchospasm requiring intensive treatment in an emergency room or at home, blood 
dyscrasias or convulsions that do not result in inpatient hospitalization, or the development of 
drug dependency or drug abuse. 
Life-threatening is defined as an AE or suspected adverse reaction that in the view of the PI 
or designee or Sponsor, its occurrence places the patient or participant at immediate risk of 
death. It does not include an AE or suspected adverse reaction that, had it occurred in a more 
severe form, might have caused death. 
Hospitalization is defined as an inpatient admission, regardless of length of stay, even if the 
hospitalization is a precautionary measure for continued observation. (Note: Hospitalization 
for an elective procedure to treat a preexisting condition that has not worsened is not an 
SAE.) A preexisting condition is a clinical condition that is diagnosed prior to the use of a 
Sponsor product and is documented in the participant’s medical history. 
Unexpected is defined as an AE or suspected adverse reaction that is not listed in the IB or is 
not listed at the specificity or severity that has been observed; or is not consistent with the 
risk information described in the general investigational plan or elsewhere in the current 
application, as amended. 
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8.2.6.3 Monitoring 
Participants will be monitored for adverse reactions to the study drug and/or procedures from 
the time of signing the ICF until the follow-up visit. Prior to release, participants will be 
asked how they are feeling. At each subsequent visit, participants will be queried with an 
open-ended question such as: ‘How have you been feeling since your last visit?’ 
AEs (whether serious or non-serious) and clinically significant abnormal laboratory test 
value(s) will be evaluated by the PI or designee and treated and/or followed up until the 
symptoms or value(s) return to normal, or acceptable levels, as judged by the PI or designee. 
Treatment of SAEs will be performed by a licensed health care professional, either at 
Celerion or at a nearby hospital emergency room where appropriate medical test(s) and/or 
examination(s) will be performed to document resolution of event(s). Outcome may be 
classified as fatal, not recovered/not resolved, recovered/resolved, recovered/resolved with 
sequelae, or recovering/resolving. 
8.2.6.4 Reporting 
All AEs that occur during this clinical study will be recorded. All clinically significant 
abnormal laboratory results should be reported as AEs. 
AEs, SAEs, and other reportable safety events that occur after the participant provides 
documented informed consent, but before dosing, must be reported by the PI or designee 
under any of the following circumstances: 
• If the participant is receiving placebo run-in or other run-in treatment. 
• If the event causes the participant to be excluded from the study. 
• If it is the result of a protocol-specified treatment, including but not limited to washout or 
discontinuation of usual therapy, diet, placebo, or a procedure. 
From the time of dosing through approximately 28 days after cessation of study drug, all 
AEs, SAEs, and other reportable safety events must be reported by the PI. 
Additionally, any SAE brought to the attention of the PI any time outside the period specified 
in the previous paragraph also must be reported immediately to the Sponsor if the event is 
considered related to study drug. 
PIs are not obligated to actively seek AEs or SAEs or other reportable safety events in former 
study participants. However, if the PI learns of any SAE, including a death, at any time after 
a participant has been discharged from the study, and the PI considers the event to be 
reasonably related to the study drug or study participation, the PI must promptly notify the 
Sponsor. 
Exception: A positive pregnancy test at the time of initial screening is not a reportable event 
unless the participant has received the study drug. 
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Assessment of causality 
• Did the study drug cause the AE? 
• The determination of the likelihood that the study drug caused the AE will be provided 
by a PI who is a qualified physician. The PI’s signed/dated initials on the source 
document or worksheet that supports the causality noted on the AE form, ensures that a 
medically qualified assessment of causality was done. This initialed document must be 
retained for the required regulatory time frame. The criteria below are intended as 
reference guidelines to assist the PI in assessing the likelihood of a relationship between 
the test product and the AE based upon the available information. 
• The following components are to be used to assess the relationship between the 
study drug and the AE; the greater the correlation with the components and their 
respective elements (in number and/or intensity), the more likely the study drug 
caused the AE: 
o Exposure: Is there evidence that the participant was actually exposed to the study 
drug such as: reliable history, acceptable compliance assessment (pill count, diary, 
etc.), expected pharmacologic effect, or measurement of drug/metabolite in bodily 
specimen? 
o Time Course: Did the AE follow in a reasonable temporal sequence from 
administration of the study drug? Is the time of onset of the AE compatible with a 
drug-induced effect (applies to studies with investigational medicinal product)? 
o Likely Cause: Is the AE not reasonably explained by another etiology such as 
underlying disease, other drug(s)/vaccine(s), or other host or environmental factors. 
o Dechallenge: Was the study drug discontinued or dose/exposure/frequency reduced? 
 If yes, did the AE resolve or improve? 
 If yes, this is a positive dechallenge. 
 If no, this is a negative dechallenge. 
(Note: This criterion is not applicable if: (1) the AE resulted in death or permanent 
disability; (2) the AE resolved/improved despite continuation of the study drug; 
(3) the study is a single-dose drug study; or (4) study drug(s) is/are only used 1 time.) 
o Rechallenge: Was the participant re-exposed to the study drug in this study? 
 If yes, did the AE recur or worsen? 
 If yes, this is a positive rechallenge. 
 If no, this is a negative rechallenge. 
(Note: This criterion is not applicable if: (1) the initial AE resulted in death or 
permanent disability, or (2) the study is a single-dose drug study; or (3) study drug(s) 
is/are used only 1 time.) 
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NOTE: IF A RECHALLENGE IS PLANNED FOR AN AE THAT WAS SERIOUS AND 
MAY HAVE BEEN CAUSED BY THE STUDY DRUG, OR IF RE-EXPOSURE TO THE 
STUDY DRUG POSES ADDITIONAL POTENTIAL SIGNIFICANT RISK TO THE 
PARTICIPANT THEN THE RECHALLENGE MUST BE APPROVED IN ADVANCE BY 
THE SPONSOR CLINICAL DIRECTOR, AND IF REQUIRED, THE IRB. 
• Consistency with study drug profile: Is the clinical/pathological presentation of the AE 
consistent with previous knowledge regarding the study drug or drug class pharmacology 
or toxicology? 
• The assessment of relationship will be reported on the CRFs/worksheets by a PI who is a 
qualified physician according to their best clinical judgment, including consideration of 
the above elements. 
• Use the following scale of criteria as guidance (not all criteria must be present to be 
indicative of a study drug relationship). 
o Yes, there is a reasonable possibility of study drug relationship: 
 There is evidence of exposure to the study drug. The temporal sequence of the AE 
onset relative to the administration of the study drug is reasonable. The AE is 
more likely explained by the study drug than by another cause. 
o No, there is not a reasonable possibility of study drug relationship: 
 Participant did not receive the study drug OR temporal sequence of the AE onset 
relative to administration of the study drug is not reasonable OR the AE is more 
likely explained by another cause than the study drug. (Also entered for a 
participant with overdose without an associated AE.) 
• The PI must review and provide an assessment of causality for each AE/SAE and 
document this in the medical notes. 
• There may be situations in which an SAE has occurred and the PI has minimal 
information to include in the initial report to the Sponsor. However, it is very important 
that the PI always make an assessment of causality for every event before the initial 
transmission of the SAE data to the Sponsor. 
• The PI may change their opinion of causality in light of follow-up information and send 
an SAE follow-up report with the updated causality assessment. 
• The causality assessment is 1 of the criteria used when determining regulatory reporting 
requirements. 
Assessment of intensity/toxicity 
Each sign or symptom reported will be graded on a 3-point severity scale (mild, moderate, or 
severe), and the date of onset, time of onset, and outcome of each event will be noted. 
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The following definitions will be used for rating the severity of AEs: 
Mild 
The AE is easily tolerated and does not interfere with daily activity. 
Moderate 
The AE interferes with daily activity, but the participant is still able to 
function. Medical intervention may be considered. 
Severe 
The AE is incapacitating and requires medical intervention. 
8.2.6.5 Reporting for SAEs 
If any AEs are serious, as defined by the FDA Code of Federal Regulations (CFR), Chapter 
21, special procedures will be followed. All SAEs will be reported to the Sponsor via fax or 
e-mail within 24 hours of becoming aware of the event, whether or not the serious events are 
deemed drug-related. This will be followed by the SAE Report within 24 hours. All serious 
event reporting will adhere to 21 CFR 312.32 for Investigational New Drugs (IND) and to 
the Guidance for Industry and Investigators: Safety Reporting Requirements for INDs and 
BA/BE, dated December 2012. The IRB will be notified of the Alert Reports as per FDA 
regulations. 
If an SAE occurs to a participant on this study, contact the Sponsor personnel listed in the 
Additional Key Contacts for the Study section. 
8.2.7 Additional Events Reported 
Additional events that require reporting 
In addition to the above criteria, AEs meeting either of the below criteria, although not 
serious per International Council for Harmonisation (ICH) definition, are reportable to the 
Sponsor. 
• Is a cancer. 
• Is associated with an overdose. 
8.2.8 Events of Clinical Interest 
Selected serious and non-serious AEs are also known as events of clinical interest (ECIs) and 
must be reported to the Sponsor. 
ECIs for this study include: 
1. An overdose of study drug, as defined in Section 8.2.9. 
2. Potential drug-induced liver injury events defined as an elevated AST or ALT laboratory 
value that is greater than or equal to 3x the upper limit of normal (ULN) and an elevated 
total bilirubin laboratory value that is greater than or equal to 2x the ULN and, at the 
same time, an alkaline phosphatase laboratory value that is less than 2x the ULN, as 
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determined by way of protocol-specified laboratory testing or unscheduled laboratory 
testing.* 
*Note: These criteria are based on available regulatory guidance documents. The purpose 
of the criteria is to specify a threshold of abnormal hepatic tests that may require an 
additional evaluation for an underlying etiology. The study-site guidance for assessment 
and follow-up of these criteria can be found in the Investigator Study File Binder (or 
equivalent). 
It may also be appropriate to conduct additional evaluation for an underlying etiology in 
the setting of abnormalities of liver blood tests including AST, ALT, bilirubin, and 
alkaline phosphatase that do not meet the criteria noted above. In these cases, the decision 
to proceed with additional evaluation will be made through consultation between the 
study investigators and the Sponsor Clinical Director. However, abnormalities of liver 
blood tests that do not meet the criteria noted above are not ECIs for this study. 
8.2.9 
Treatment of Overdose 
For purposes of this study, an overdose will be defined as any dose of any drug administered 
as part of the study exceeding the dose prescribed by the protocol. It is up to the PI or the 
reporting physician to decide whether a dose is to be considered an overdose, in consultation 
with the Sponsor. 
Refer to the IB for specific treatment of overdose. Decisions regarding dose interruptions or 
modifications will be made by the PI or designee in consultation with the Sponsor Clinical 
Director based on the clinical evaluation of the participant. 
8.3 
Pharmacokinetic Assessments 
8.3.1 
Blood Sampling and Processing 
For all participants, blood samples for the determination of MK-8527 and MK-8527-TP will 
be collected at scheduled time points as delineated in the Schedule of Activities (Section 1.3). 
Instructions for blood sampling, collection, processing, and sample shipment will be 
provided separately. 
The allowed window for PK blood sampling is indicated in Table 2. 
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Table 2: Window for PK Blood Sample Collection 
Nominal Time 
Allowed Window 
Predose 
Within 30 minutes prior to dosing 
> 0 to < 1 hour 
≤ ± 5 minutes 
1 to < 2 hours 
≤ ± 10 minutes 
2 to < 24 hours 
≤ ± 15 minutes 
24 to < 48 hours 
≤ ± 1 hour 
48 to ≤ 168 hours 
≤ ± 4 hours 
> 168 to < 672 hours 
≤ ± 24 hours 
≥ 672 hours 
≤ ± 48 hours 
8.3.2 Plasma and PBMC Pharmacokinetic Parameters 
The following PK parameters for plasma MK-8527 and PBMC MK-8527-TP will be 
calculated, as appropriate: 
AUC0-last: 
Area under the concentration versus time curve from 0 to the time 
of the last quantifiable (above lower limit of quantitation) sample 
AUC0-inf: 
Area under the concentration versus time curve from 0 to infinity 
after single dosing 
AUC%extrap: 
Percent of AUC0-inf extrapolated 
CL/F: 
Apparent clearance (plasma MK-8527 only) 
Cmax: 
Maximum observed drug concentration after the administration of 
a given dose 
C168: 
Drug concentration at Hour 168 (PBMC MK-8527-TP only) 
C672: 
Drug concentration at Hour 672 (PBMC MK-8527-TP only) 
Tmax: 
Time to maximum observed drug concentration 
λz: 
Lambda z, Apparent terminal elimination rate constant 
t½: 
Apparent terminal half-life 
Vz/F: 
Apparent volume of distribution during terminal phase (plasma 
MK-8527 only) 
No value for λz, AUC0-inf, AUC%extrap, CL/F, Vz/F, or t½ will be reported for cases that 
do not exhibit a terminal log-linear phase in the concentration-time profile. 
PK parameters will not be calculated for participants with less than 3 consecutive postdose 
time points with quantifiable concentrations. 
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8.3.3 Urine Sampling and Processing 
Urine for PK assessments will be collected at the specified intervals delineated in the 
Schedule of Activities (Section 1.3). Urine samples will be collected per schedule whenever 
possible, as some participants with RI may not be able to produce urine during each 
collection interval. 
Prior to the predose sample, each participant will be instructed as to urine collection methods. 
All urine during an interval is to be collected. 
On Day 1, a spot collection will be obtained prior to dosing for the predose sample. 
Participants will be asked again to empty their bladder within approximately 15 minutes prior 
to dosing, and no urine will be collected at this time unless it is needed for the predose 
sample. Only one predose urine sample will be collected on Day 1. 
Participants will be encouraged to void at the end of each collection interval. If they do void 
at any time during the collection interval, the time should be documented. Should this be the 
case, participants need to void again at the end of the collection period, as scheduled. 
However, should participants be unable to void, this will be documented as well.  
Urine will be refrigerated during the collection intervals. At the end of each interval, urine 
will be pooled and thoroughly mixed. Total urine volume will be weighed and recorded.  
Instructions for urine sampling, collection, processing, and sample shipment will be provided 
separately. 
8.3.4 Urine Pharmacokinetic Parameters 
The following PK parameters for urine MK-8527 will be calculated, as appropriate: 
Ae: 
Amount of unchanged drug excreted in urine (cumulative or during a 
collection interval) 
CLr: 
Renal clearance calculated as Ae(t’-t”)/AUC(t’-t”) where t’-t” is the 
longest interval of time during which Ae and AUC are both obtained  
fe: 
Fraction (in percentage) of dose excreted in urine 
8.3.5 Long Term Storage and Use 
Any residual plasma, PBMC, and/or urine from the PK samples will be stored by the Sponsor 
or bioanalytical facility for up to 15 years after dosing and may be used for future analyses 
(e.g., PK assessment). Tubes will be identified with a barcode using an appropriate label. No 
diseases/conditions, deoxyribonucleic acid (DNA), or ribonucleic acid (RNA) will be the 
focus of these analyses. The analyses will only focus on analytes/biomarkers. Samples will 
not be submitted to a public database. The Sponsor and contract research organizations 
involved in the clinical conduct, bioanalytical analyses and PK and statistical analyses of the 
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data will have access to the samples and/or the data that resulted from the analysis, if 
performed. By signing the ICF, participants agree to the possible future analysis of these 
samples. Any additional research on these samples unspecified by this protocol will require 
approval from the participants. 
8.3.6 Analytical Method 
Samples from all participants will be assayed even if the participants do not complete the 
study. 
Samples will be analyzed for plasma MK-8527, PBMC MK-8527-TP, and urine MK-8527 
using validated bioanalytical methods. 
If indicated, these samples may also be measured and/or pooled for assay in an exploratory 
manner for metabolites and/or additional pharmacodynamic markers. 
8.4 
Planned Exploratory Biomarker Research 
8.4.1 Biomarkers 
8.4.1.1 Planned Genetic Analysis 
Genetic variation may impact a participant’s response to therapy, susceptibility to, severity, 
and progression of disease. Variable response to therapy may be due to genetic determinants 
that impact drug absorption, distribution, metabolism, and excretion; mechanism of action of 
the drug; disease etiology; and/or molecular subtype of the disease being treated. Therefore, 
where local regulations and IRB allow, a sample will be collected for DNA analysis from 
consenting participants. 
DNA samples may be used for research related to the study drug(s), the disease under study, 
or related diseases. They may also be used to develop tests/assays including diagnostic tests 
related to the disease under study, related diseases, and study drug(s). Genetic research may 
consist of the analysis of 1 or more candidate genes, the analysis of genetic markers 
throughout the genome, or analysis of the entire genome. Analysis may be conducted if it is 
hypothesized that this may help further understand the clinical data. 
The samples may be analyzed as part of a multistudy assessment of genetic factors involved 
in the response to understand study disease or related conditions. 
8.4.1.1.1 Planned Genetic Analysis Sample Collection 
The planned genetic analysis sample should be collected for planned analysis of the 
association between genetic variants in DNA and drug response. This sample will not be 
collected at the site if there is either a local law or regulation prohibiting collection, or if the 
IRB does not approve the collection of the sample for these purposes. If the sample is 
collected, leftover extracted DNA will be stored for FBR if the participant provides 
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documented informed consent for FBR. If the planned genetic analysis is not approved, but 
FBR is approved, this sample will be collected for the purpose of FBR. 
The planned genetic analysis sample should be obtained predose on Day 1, but may be 
collected at the next scheduled blood draw, if needed. Sample collection, storage, and 
shipment instructions for planned genetic analysis samples will be in the 
operations/laboratory manual. 
8.4.2 Future Biomedical Research 
The Sponsor will conduct FBR on DNA specimens for which consent was provided during 
this clinical study. 
Such research is for biomarker testing to address emergent questions not described elsewhere 
in the protocol and will only be conducted on specimens from appropriately consented 
participants. The objective of collecting/retaining specimens for FBR is to explore and 
identify biomarkers that inform the scientific understanding of diseases and/or their 
therapeutic treatments. The overarching goal is to use such information to develop safer, 
more effective drugs/vaccines, and/or to ensure participants receive the correct dose of the 
correct drug/vaccine at the correct time. The details of FBR research are presented in 
Appendix 1. 
8.4.2.1 Future Biomedical Research Sample Collection 
All sample collections for study-specific assessments shown in the Schedule of Activities 
(Section 1.3) are described within the main informed consent. 
If the participant has provided documented informed consent for FBR, leftover samples will 
be used for FBR. The following specimens will be included for FBR: 
• Leftover samples listed in Section 8.4.1 
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8.5 
Blood Volume Drawn for Study Assessments 
Table 3: Blood Volume during the Study 
Sample Type 
Number of 
Time 
Points 
Approximate 
Volume per Time 
Point * (mL) 
Approximate Sample 
Volume Over Course 
of Study (mL) 
Screening laboratory safety tests 
(including hematology, serum chemistry, 
and serology), FSH (for postmenopausal 
female participants only), and serum 
pregnancy (for female participants only) 
1 
12.5 
12.5 
Blood for planned genetic analysis 
1 
8.5 
8.5 
On-study hematology and serum 
chemistry (this includes serum pregnancy 
for female participants only when 
scheduled at the same time) 
3 
12.5 
37.5 
Blood for immunophenotyping 
4 
10 
40 
Blood for plasma MK-8527 
16 
3 
48 
Blood for PBMC MK-8527 
12 
16 
192 
Total Blood Volume (mL)→ 
338.5 ** 
* 
A smaller or larger collection tube size may be used if the present collection tube size is not available. 
** 
If additional blood is needed for safety or PK analysis, additional blood may be collected (up to a 
maximum of 500 mL for the study). 
 
 
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9 
STATISTICAL CONSIDERATIONS 
Data will be handled and processed according to Celerion Standard Operating Procedures, 
which are written based on the principles of GCP. 
9.1 
Sample Size Determination 
The between-participant standard deviations (on the natural log [ln] scale) for plasma 
MK-8527 AUC0-inf and Cmax, and for PBMC MK-8527-TP AUC0-inf and Cmax after 
administration of MK-8527 observed in a previous study (MK-8527-003) are 0.253 
ln(h*nmol/L), 0.313 ln(nmol/L), 0.213 ln(h*pmol/106 cells) and 0.262 ln(pmol/106 cells), 
respectively. Assuming the same variability for 6 mg MK-8527, with 6 severe RI 
participants, 6 moderate RI participants, and 6 healthy participants, the half-width of the 90% 
confidence intervals (CIs) of geometric mean ratios (GMRs) for plasma MK-8527 AUC0-inf 
and Cmax, and for PBMC MK-8527-TP AUC0-inf and Cmax on the log scale will be 0.196, 
0.242, 0.165, and 0.203 respectively. The lower and upper 90% confidence limits for the true 
GMRs will be given by OBS/1.21 and OBS*1.21 for plasma MK-8527 AUC0-inf, OBS/1.27, 
and OBS*1.27 for plasma MK-8527 Cmax, OBS/1.18 and OBS*1.18 for AUC0-inf 
MK-8527-TP in PBMC, OBS/1.22, and OBS*1.22 for Cmax MK-8527-TP in PBMC, where 
OBS is the observed least squares geometric mean ratio. 
9.2 
Population for Analyses 
The following populations are defined for the analysis and reporting of data. All participants 
will be reported, and their data analyzed, according to the treatment(s) they actually received. 
All Participants as Treated (APaT): The APaT Population consists of all participants who 
received the study drug. This population will be used for assessments of safety and 
tolerability. 
Per-Protocol (PP): The PP Population consists of the subset of participants who comply with 
the protocol sufficiently to ensure that generated data will be likely to exhibit the effects of 
treatment, according to the underlying scientific model. Compliance covers such 
considerations as exposure to study drug, availability of measurements and absence of 
important protocol deviations. Important protocol deviations will be identified to the extent 
possible prior to database lock. Any participants or data values excluded from analysis will 
be identified, along with their reason for exclusion, in the CSR. At the end of the study, all 
participants who are compliant with the study procedure as aforementioned and have 
available data considered sufficient to exhibit the effect of treatment will be included in the 
PP dataset. This population will be used for the PK analyses. 
9.3 
Statistical Analyses 
Detailed methodology for summary and statistical analyses of the data collected in this study 
will be documented in a Statistical Analysis Plan (SAP). The SAP will be prepared by 
Celerion and agreed upon with the Sponsor. This document may modify the plans outlined in 
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the protocol; however, any major modifications of the primary endpoints definition and/or its 
analysis will also be reflected in a protocol amendment. Additional statistical analyses other 
than those described in this section may be performed if deemed appropriate. 
The statistical analysis of the data obtained from this study will be conducted by, or under the 
direct auspices of, the Early Clinical Development Statistics Department in collaboration 
with the Quantitative Pharmacology and Pharmacometrics Department and Translational 
Medicine Department of the Sponsor. 
If, after the study has begun, changes are made to the statistical analysis stated below, then 
these deviations to the plan will be listed, along with an explanation as to why they occurred, 
in the Clinical Study Report. 
9.3.1 Pharmacokinetic Analyses 
9.3.1.1 Descriptive Statistics 
The plasma and urine MK-8527 and PBMC MK-8527-TP concentrations and the PK 
parameters listed in Section 8.3.2 and Section 8.3.4 will be summarized using the appropriate 
descriptive statistics which will be fully outlined in the SAP. 
9.3.1.2 Renal Function Categorization 
For study eligibility and primary analysis, participants will be categorized using de-indexed 
eGFR values (with eGFR expressed as mL/min) calculated at screening. 
For additional analyses, participants will also be re-categorized into renal function groups 
using indexed eGFR values from the 2021 CKD-EPI creatinine equation (with eGFR 
expressed as mL/min/1.73 m2), calculated from values collected at screening. 
Summary Statistics using De-indexed eGFR 
The participants will be categorized into different renal categories based on their de-indexed 
eGFR. Non-model based summary statistics by population will be provided for plasma MK-
8527 AUC0-last, AUC0-inf, Cmax, Tmax, t½, CL/F, and Vz/F, and for PBMC MK-8527 
AUC0-last, AUC0-inf, Cmax, C168, C672, Tmax, and t½. 
Summary Statistics using the 2021 CKD-EPI Creatinine Equation 
The participants will be re-categorized into different renal categories based on their indexed 
eGFR calculated using the 2021 CKD-EPI creatinine equation. Non-model based summary 
statistics by population will be provided for plasma MK-8527 AUC0-last, AUC0-inf, Cmax, 
Tmax, t½, CL/F, and Vz/F, and for PBMC MK-8527-TP AUC0-last, AUC0-inf, Cmax, 
C168, C672, Tmax, and t½. 
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9.3.1.3 Statistical Analyses for Plasma MK-8527 and PBMC MK-8527-TP 
Separately for each PK parameter, individual values of plasma MK-8527 AUC0-last, 
AUC0-inf, and Cmax, of PBMC MK-8527-TP AUC0-last, AUC0-inf, Cmax, C168, and 
C672, after a single-dose administration of MK-8527 to participants with severe and 
moderate RI and to healthy control participants will be ln-transformed and evaluated with a 
linear fixed effects model containing a categorical effect for population (participants with 
severe RI, with moderate RI, and healthy control participants). An unstructured covariance 
matrix will be used to allow for unequal population variances via the REPEATED and 
GROUP statement in SAS PROC MIXED. Kenward and Roger’s method will be used to 
calculate the denominator degrees of freedom for the fixed effect (DDFM=KR). Ninety-five 
percent (95%) CIs for the least-squares means (LSM) for each population will be constructed 
on the ln scale and will reference the t-distribution. Exponentiating the LSM and their 
corresponding 95% confidence limits will yield estimates for the population geometric means 
and CIs about the geometric means on the original scale. 
Sample SAS code is given below: 
proc mixed data=data; 
class population ; 
model lnpk = population /ddfm=kr; 
repeated/ group= population type=UN; 
lsmeans population /cl alpha=0.05; 
run; 
To address the primary and secondary estimation objectives and compare participants with 
severe RI or moderate RI to healthy control participants with normal renal function, a two-
sided 90% CI for the true difference in means (participants with severe RI – healthy control 
participants) and true difference in means (participants with moderate RI – healthy control 
participants) will be calculated for each PK parameter using the mean square error from the 
model and referencing a t-distribution. These confidence limits will be exponentiated to 
obtain the 90% CI for the true ratio of geometric means (participants with severe RI/healthy 
control participants) and (participants with moderate RI/healthy control participants) for each 
PK parameter. 
Individual values will be listed for each PK parameter (plasma MK-8527 AUC0-last, 
AUC0-inf, Cmax, Tmax, t½, CL/F, and Vz/F; PBMC MK-8527-TP AUC0-last, AUC0-inf, 
Cmax, C168, C672, Tmax, and t½) by population, and the following (non-model-based) 
descriptive statistics will be provided: n (number of participants with non-missing data), 
arithmetic mean, standard deviation, arithmetic percent coefficient of variation (CV; 
calculated as 100 x standard deviation/arithmetic mean), median, minimum, maximum, 
geometric mean, and geometric percent CV (calculated as 100 x sqrt(exp(s2) - 1), where s2 is 
the observed variance on the ln scale). 
Figures showing individual PK values with geometric means (95% CIs) by population, 
plotted on the ln scale, will be provided for plasma MK-8527 AUC0-last, AUC0-inf, and 
Cmax, and for PBMC MK-8527-TP AUC0-last, AUC0-inf, Cmax, C168, and C672. 
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Individual participant PK values will also be plotted against indexed eGFR using each 
individual’s BSA, using different symbols to identify participants from each population. For 
this analysis, eGFR will be calculated as the mean of the two values determined at screening. 
Additionally, plots of PK parameter values versus age, BMI, and/or sex may be provided. 
Statistical modelling of the relationship between renal function (based on de-indexed eGFR) 
and PK parameters using linear (and non-linear as appropriate) regression analysis of eGFR 
versus AUC and Cmax (total and unbound) may be performed. 
9.3.1.4 Statistical Analysis for Urine MK-8527 
The amount of MK-8527 excreted in the urine collection interval from the time of dosing 
through 48 hours (Ae0-48) will be determined from the urine concentration and volume data. 
The fraction, fe, of MK-8527 excreted in urine expressed as a % MK-8527 administered dose 
will be determined. CLr of MK-8527 will be calculated from the urine Ae and plasma AUC 
available for the same time period (e.g., Ae0-48 and AUC0-48). Urinary drug clearance for 
each urine collection interval will be calculated for each group (with de-indexed eGFR 
expressed as mL/min). A descriptive summary of MK-8527 urine collection may be 
provided. 
9.3.1.5 Multiplicity 
There is no pre-specified hypothesis; therefore, no multiplicity adjustment is needed. 
9.3.2 Safety Analyses 
AEs will be coded using the most current version of Medical Dictionary for Regulatory 
Activities available at Celerion and summarized by group for the number of participants 
reporting the TEAE and the number of TEAEs reported. A by-participant AE data listing 
including verbatim term, coded term, treatment, severity, action, and relationship to treatment 
will be provided.  
Safety data including clinical laboratory results, immunophenotyping results, vital sign 
assessments, and 12-lead ECGs will be summarized by time point of collection. 
Quantitative safety data as well as the change from baseline, when appropriate, will be 
summarized using the appropriate descriptive statistics. 
Concomitant medications will be listed by participant and coded using the most current 
version of World Health Organization Drug Dictionary available at Celerion. 
Medical history will be listed by participant. 
9.3.3 Interim Analysis 
Not applicable. 
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10 STUDY ADMINISTRATION  
10.1 Ethics 
10.1.1 Institutional Review Board 
This protocol will be reviewed by an IRB and the study will not start until the IRB has 
approved the protocol or a modification thereof. The IRB is constituted and operates in 
accordance with the principles and requirements described in the US Code of Federal 
Regulations (21 CFR Part 56). The IRB is ICH compliant. 
10.1.2 Ethical Conduct of the Study 
This research will be carried out in accordance with the protocol, US Code of Federal 
Regulations, 21 CFR Parts 50, 56, and 312, the ethical principles set forth in the Declaration 
of Helsinki, GCP, and the ICH harmonized tripartite guideline regarding GCP (E6[R2] Good 
Clinical Practice: Integrated Addendum to E6 [R1], November 2016). 
10.1.3 Participant Informed Consent 
The purpose of the study, the procedures to be carried out and the potential hazards will be 
described to the participants in non-technical terms. Participants will be required to read, sign 
and date an ICF summarizing the discussion prior to screening, and will be assured that they 
may withdraw from the study at any time without jeopardizing their medical care. 
10.1.3.1 General Informed Consent 
Informed consent given by the participant must be documented on a consent form. The form 
must include the study protocol number, study protocol title, dated signature, and agreement 
of the participant and of the person conducting the consent discussion. 
A copy of the signed and dated ICF will be given to the participant before participating in the 
study, or FBR. 
The initial ICF, any subsequent revised ICF, and any written information provided to the 
participant must receive the IRB’s approval/favorable opinion in advance of use. The 
participant or his/her legally acceptable representative should be informed in a timely manner 
if new information becomes available that may be relevant to the participant’s willingness to 
continue participation in the study. The communication of this information will be provided 
and documented via a revised consent form or addendum to the original consent form that 
captures the participant’s or the participant’s legally acceptable representative’s dated 
signature. 
Specifics about the study and the study population are to be included in the study informed 
consent form. 
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Informed consent will adhere to IRB requirements, applicable laws and regulations, and 
Sponsor requirements. 
10.1.3.2 Consent and Collection of Specimens for Future Biomedical Research 
The PI or designee will explain the FBR consent to the participant, answer all of his/her 
questions, and obtain documented informed consent before performing any procedure related 
to FBR. 
A copy of the signed and dated informed consent will be given to the participant before 
performing any procedure related to FBR. 
10.1.4 Confidentiality 
All clinical sites and vendors will have signed confidentiality agreements with Celerion. By 
signing this protocol, the PI and CRU staff will regard all information provided by the 
Sponsor and all information obtained during the course of the study as confidential.  
The clinical site and Celerion must guarantee the privacy of the participants taking part in the 
study. Participants will be identified throughout documentation and evaluation by a unique 
participant study number. Throughout the study, a participant’s source data will only be 
linked to the Sponsor’s clinical study database or documentation via a unique identification 
number. If participant name appears on any study document, it must be redacted before the 
copy of the documents is supplied to the Sponsor. Any information concerning the 
participants (clinical notes, identification numbers, etc.) must be kept on file by the PI or 
designee who will ensure that it is revealed only to the Sponsor, IRB, or regulatory 
authorities for the purposes of trial monitoring, auditing or official inspections. As required, 
in the case of an event where medical expenses are the responsibility of the Sponsor, personal 
information i.e., full name, social security details etc. may be released to the Sponsor. 
Appropriate precautions will be taken to maintain confidentiality of medical records and 
personal information in strictest confidence and in accordance with local data protection 
laws. 
10.2 Study Termination 
The CRU(s) reserves the right to terminate the study in the interest of participant welfare. 
The Sponsor reserves the right to suspend or terminate the study at any time. 
10.3 Data Management 
Data management activities will be detailed in the Data Management Plan (DMP). Each 
vendor involved with this study will adhere to Good Documentation Practices and their 
standard operating procedures covering their respective activities relevant to participation in 
this study, as applicable. The PI or designee will ensure that all data related to the conduct of 
this study is attributable, legible, contemporaneous, original, accurate, enduring, and readily 
accessible. 
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Standard operating procedures are available for all activities performed at the CRU relevant 
to the quality of this study. Designated personnel of the CRU will be responsible for 
implementing and maintaining quality assurance (QA) and quality control systems to ensure 
that the study is conducted, and that data are generated, documented and reported in 
compliance with the study protocol, and GCP requirements as well as applicable regulatory 
requirements and local laws, rules and regulations relating to the conduct of the clinical 
study. 
The Clinical Study Report will be audited by the QA department and the QA audit certificate 
will be included in the Clinical Study Report. 
10.3.1 Data Entry and Verification 
Data will be transcribed from original sources by the PI or designee into the CRF. Data 
received from external sources, as applicable, will be integrated into the Clinical Data 
Interchange Standards Consortium study data tabulation model datasets. 
10.3.2 Data Validation 
After the data have been entered, various edit checks (including manual review of listings) 
will be performed to ensure the accuracy, integrity and validation of the database against the 
CRF as described in the DMP.  
Inconsistencies that arise from these edit checks will be resolved with the PI or designee. 
10.3.3 Database Lock 
Upon study completion, after data entry is complete, the data has been pronounced clean, and 
the PI has reviewed and provided approval via signature, the database will be locked and 
final write access will be removed. 
The Sponsor will be required to provide database lock approval. 
Any changes to the data following database lock will be documented and approved by the 
Sponsor prior to unlocking the database to make changes to the data. 
The final transfer of all study data to the Sponsor will be in SAS format with supporting 
documentation as described in the DMP. 
10.4 Direct Access to Source Data/Documents 
All CRUs and vendors will ensure that the Sponsor, IRB and inspection by domestic and 
foreign regulatory authorities will have direct access to all study-related sites, source 
data/documents, and reports for the purpose of monitoring and auditing 
(ICH[E6][R2] 5.1.2 & 6.10). In the event that other study-related monitoring should be done 
by other parties, they will be required to sign a confidentiality agreement prior to any 
monitoring and auditing. 
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10.5 Reporting of the Study 
10.5.1 Case Report Forms 
A CRF is completed for each dosed participant whether or not the participant has completed 
the study. The PI will assure complete and accurate entries on the forms. Each CRF will be 
reviewed and signed by the PI. The final signed CRFs will be archived electronically at the 
end of study in a document repository system. Final CRFs will be provided to the Sponsor in 
the format and transfer method as decided between Celerion and the Sponsor which will be 
documented in the DMP. 
10.5.2 Record Keeping 
Records and documents, including participants’ documented informed consent, pertaining to 
the conduct of this study must be retained by the PI for 15 years after study completion 
unless local regulations or institutional policies require a longer retention period. No records 
may be destroyed during the retention period without the written approval of the Sponsor. No 
records may be transferred to another location or party without written notification to the 
Sponsor. 
It is the responsibility of the Sponsor to inform the PI/Institution as to when these documents 
no longer need to be retained. 
10.5.3 Report Format 
According to the ICH Harmonized Tripartite Guideline (Organization of the Common 
Technical Document for the Registration of Pharmaceuticals for Human Use M4 and the 
ICH M2 Expert Working Group), the final clinical study report will be written according to 
the ICH E3 Guideline (Structure and Content of Clinical Study Reports).  
10.6 Publication Policy 
All unpublished information given to Celerion and/or the CRU by the Sponsor shall not be 
published or disclosed to a third party without the prior written consent of the Sponsor. 
The data generated by this study are considered confidential information and the property of 
the Sponsor. This confidential information may be published only in collaboration with 
participating personnel from the Sponsor or upon Sponsor’s written consent to publish the 
article. 
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11 REFERENCES 
Food and Drug Administration: Center for Drug Evaluation and Research (CDER). Guidance 
for Industry. Pharmacokinetics in Patients with Impaired Renal Function - Study Design, 
Data Analysis, and Impact on Dosing. Draft Guidance. Sep 2020. 
Global HIV & AIDS statistics - Fact sheet. UNAIDS. https://www.unaids.org/en/resources/ 
fact-sheet. Published 2023. Accessed 26Oct2023. 
 
 
 
 
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12 APPENDICES 
12.1 Appendix 1: Collection and Management of Specimens for Future Biomedical 
Research 
1. Definitions 
a. Biomarker: A biological molecule found in blood, other body fluids, or tissues that is 
a sign of a normal or abnormal process or of a condition or disease. A biomarker may 
be used to see how well the body responds to a treatment for a disease or condition.1 
b. Pharmacogenomics: The investigation of variations of DNA and RNA characteristics 
as related to drug/vaccine response.2 
c. Pharmacogenetics: A subset of pharmacogenomics, pharmacogenetics is the influence 
of variations in DNA sequence on drug/vaccine response.2 
d. DNA: Deoxyribonucleic acid. 
e. RNA: Ribonucleic acid. 
2. Scope of Future Biomedical Research 3, 4 
The specimens consented and/or collected in this study as outlined in Section 8.4.1 will 
be used in various experiments to understand: 
• The biology of how drugs/vaccines work 
• Biomarkers responsible for how a drug/vaccine enters and is removed by the body 
• Other pathways with which drugs/vaccines may interact 
• The biology of disease 
The specimen(s) may be used for future assay development and/or drug/vaccine 
development. 
It is now well recognized that information obtained from studying and testing clinical 
specimens offers unique opportunities to enhance our understanding of how individuals 
respond to drugs/vaccines, enhance our understanding of human disease and ultimately 
improve public health through development of novel treatments targeted to populations 
with the greatest need. All specimens will be used by the Sponsor or those working for or 
with the Sponsor. 
3. Summary of Procedures for Future Biomedical Research 3, 4 
a. Participants for Enrollment 
All participants enrolled in the clinical study will be considered for enrollment in 
future biomedical research. 
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b. Informed Consent 
Informed consent for specimens (i.e., DNA, RNA, protein, etc.) will be obtained 
during screening for protocol enrollment from all participants at a study visit by the 
PI or designee. Informed consent for FBR should be presented to the participants on 
the visit designated in the Schedule of Activities (Section 1.3). If delayed, present 
consent at next possible Participant Visit. Consent forms signed by the participant 
will be kept at the clinical study site under secure storage for regulatory reasons. 
A template of each study site’s approved informed consent will be stored in the 
Sponsor’s clinical document repository. 
c. eCRF Documentation for Future Biomedical Research Specimens 
Documentation of participant consent for future biomedical research will be captured 
in the eCRFs. Any specimens for which such an informed consent cannot be verified 
will be destroyed. 
d. Future Biomedical Research Specimen(s) 
Collection of specimens for FBR will be performed as outlined in the Schedule of 
Activities (Section 1.3). In general, if additional blood specimens are being collected 
for FBR, these will usually be obtained at a time when the participant is having blood 
drawn for other study purposes. 
4. Confidential Participant Information for Future Biomedical Research 3, 4 
In order to optimize the research that can be conducted with FBR specimens, it is critical 
to link participants’ clinical information with future test results. In fact, little or no 
research can be conducted without connecting the clinical study data to the specimen. 
The clinical data allow specific analyses to be conducted. Knowing participant 
characteristics like sex, age, medical history, and intervention outcomes are critical to 
understanding clinical context of analytical results. 
To maintain privacy of information collected from specimens obtained for FBR, the 
Sponsor has developed secure policies and procedures. All specimens will be single 
coded per ICH E15 guidelines as described below. 
At the clinical study site, unique codes will be placed on the FBR specimens. This code is 
a random number which does not contain any personally identifying information 
embedded within it. The link (or key) between participant identifiers and this unique code 
will be held at the study site. No personal identifiers will appear on the specimen tube. 
5. Biorepository Specimen Usage 3, 4 
Specimens obtained for the Sponsor will be used for analyses using good scientific 
practices. Analyses using the future biomedical research specimens may be performed by 
the Sponsor, or an additional third party (e.g., a university investigator) designated by the 
Sponsor. The investigator conducting the analysis will follow the Sponsor’s privacy and 
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confidentiality requirements. Any contracted third party analyses will conform to the 
specific scope of analysis outlined in FBR protocol and consent. FBR specimens 
remaining with the third party after specific analysis is performed will be reported to the 
Sponsor. 
6. Withdrawal From Future Biomedical Research 3, 4 
Participants may withdraw their consent for FBR and ask that their biospecimens not be 
used for FBR. Participants may withdraw consent at any time by contacting the PI. If 
medical records for the study are still available, the PI will contact the Sponsor using the 
designated mailbox (clinical.specimen.management@merck.com). Subsequently, the 
participant’s specimens will be flagged in the biorepository and restricted to study use 
only. If specimens were collected from study participants specifically for FBR, these 
specimens will be removed from the biorepository and destroyed. Documentation will be 
sent to the PI confirming withdrawal and/or destruction, if applicable. It is the 
responsibility of the PI to inform the participant of completion of the withdrawal and/or 
destruction, if applicable. Any analyses in progress at the time of request for 
withdrawal/destruction or already performed before the request being received by the 
Sponsor will continue to be used as part of the overall research study data and results. No 
new analyses would be generated after the request is received. 
If the medical records for the study are no longer available (e.g., if the PI is no longer 
required by regulatory authorities to retain the study records) or the specimens have been 
completely anonymized, there will no longer be a link between the participant’s personal 
information and their specimens. In this situation, the request for withdrawal of consent 
and/or destruction cannot be processed. 
7. Retention of Specimens 
FBR specimens will be stored in the biorepository for potential analysis for up to 
20 years from the end of the study. Specimens may be stored for longer if a regulatory or 
governmental authority has active questions that are being answered. In this special 
circumstance, specimens will be stored until these questions have been adequately 
addressed. 
Specimens from the study site will be shipped to a central laboratory and then shipped to 
the Sponsor-designated biorepository. If a central laboratory is not utilized in a particular 
study, the study site will ship directly to the Sponsor-designated biorepository. The 
specimens will be stored under strict supervision in a limited access facility which 
operates to assure the integrity of the specimens. Specimens will be destroyed according 
to Sponsor policies and procedures and this destruction will be documented in the 
biorepository database. 
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8. Data Security 3, 4 
Databases containing specimen information and test results are accessible only to the 
authorized Sponsor representatives and the designated study administrator research 
personnel and/or collaborators. Database user authentication is highly secure, and is 
accomplished using network security policies and practices based on international 
standards to protect against unauthorized access. 
9. Reporting of Future Biomedical Research Data to Participants 3, 4 
No information obtained from exploratory laboratory studies will be reported to the 
participant, family, or physicians. Principle reasons not to inform or return results to the 
participant include: lack of relevance to participant health, limitations of predictive 
capability, and concerns regarding misinterpretation. 
If important research findings are discovered, the Sponsor may publish results, present 
results in national meetings, and make results accessible on a public website in order to 
rapidly report this information to doctors and participants. Participants will not be 
identified by name in any published reports about this study or in any other scientific 
publication or presentation. 
10. Future Biomedical Research Study Population 3, 4 
Every effort will be made to recruit all participants diagnosed and treated on Sponsor 
clinical studies for FBR. 
11. Risks Versus Benefits of Future Biomedical Research 3, 4 
For FBR, risks to the participant have been minimized and are described in the FBR 
informed consent. 
The Sponsor has developed strict security, policies, and procedures to address participant 
data privacy concerns. Data privacy risks are largely limited to rare situations involving 
possible breach of confidentiality. In this highly unlikely situation, there is risk that the 
information, like all medical information, may be misused. 
12. Questions 
Any questions related to the FBR should be emailed directly to 
clinical.specimen.management@merck.com. 
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13. References 
1. National Cancer Institute [Internet]: Available from 
https://www.cancer.gov/publications/dictionaries/cancer-terms?cdrid=45618 
2. International Council on Harmonisation [Internet]: E15: Definitions for Genomic 
Biomarkers, Pharmacogenomics, Pharmacogenetics, Genomic Data and Sample 
Coding Categories. Available from 
http://www.ich.org/products/guidelines/efficacy/efficacy-single/article/definitions-
for-genomic-biomarkers-pharmacogenomics-pharmacogenetics-genomic-data-and-
sample-cod.html  
3. Industry Pharmacogenomics Working Group [Internet]: Understanding the Intent, 
Scope and Public Health Benefits of Exploratory Biomarker Research: A Guide for 
IRBs/IECs and Investigational Site Staff. Available at http://i-pwg.org/  
4. Industry Pharmacogenomics Working Group [Internet]: Pharmacogenomics 
Informational Brochure for IRBs/IECs and Investigational Site Staff. Available at 
http://i-pwg.org/ 
 
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