A Phase 1, Single Part, Partially Randomised, Open-Label Study to Evaluate the Relative Bioavailability of a Taste-Masked Delafloxacin Powder for Oral Suspension With Oral Delafloxacin Tablet Reference in Healthy Subjects
Phase: PHASE1
Conditions: Healthy
Sponsor: Melinta Therapeutics, Inc.

Doc No:DOC-174016    
  Doc Name:QSC300553 Clinical Protocol 
Project Number:QSC300553 
 Version:1.0  
Status:Approved 
Governing SOP: DOC-02642 
CLINICAL STUDY PROTOCOL 
A Phase 1, Single Part, Partially Randomised, Open-Label 
Study to Evaluate the Relative Bioavailability of a Taste-Masked 
Delafloxacin Powder for Oral Suspension with Oral Delafloxacin 
Tablet Reference in Healthy Subjects  
Short Study Title: Evaluation of the Relative Bioavailability of a 
Taste-Masked Delafloxacin Powder for Oral Suspension with 
Oral Delafloxacin Tablet Reference  
Quotient Sciences Study Number: 
QSC300553 
Sponsor Study Number: 
ML-DEL-101-3727-1
IRAS ID: 
1009679 
Clinical Study Site: 
Quotient Sciences 
Mere Way 
Ruddington Fields 
Ruddington 
Nottingham NG11 6JS, UK 
Tel: 
 
Sponsor: 
Melinta Therapeutics, LLC 
300 Tri-State International, Suite 272 
Lincolnshire 
IL 60069, USA 
Tel:
 
Date of Protocol: 
19 Mar 2024 
Status of Protocol: 
Version 1.0 
SPONSOR/QUOTIENT SCIENCES CONFIDENTIAL 
This clinical protocol may not be reproduced or communicated to a third party 
without the written permission of Melinta Therapeutics, LLC. 
NCT #: NCT06612255

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Document History 
Protocol Version Number 
Classification 
Date  
1.0 
N/A  
19 Mar 2024 
 

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Study Contacts 
Principal Investigator: 
 
Quotient Sciences 
Mere Way 
Ruddington Fields 
Ruddington 
Nottingham NG11 6JS, UK 
Tel: 
 (day) 
Tel: 
 (out of hours emergency) 
Sub-Investigators: 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Quotient Sciences 
Tel: 
 (day) 
Tel: 
 (out of hours emergency) 
Scientific Lead: 
 
Quotient Sciences  
Tel: 
 (day)  
Programme Manager: 
 
Quotient Sciences 
Tel: 
 
Project Manager: 
 
Quotient Sciences 
Tel: 
 
Study Monitor: 
Bionical Emas 
Suite 209 
Spirella Building 
Bridge Road 
Letchworth Garden City 
Hertfordshire SG6 4ET, UK 
Tel: 
 

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Medical Monitor: 
 
Melinta Therapeutics, LLC 
389 Interpace Parkway, Suite 450 
Parsippany, NJ 07054, USA 
Tel: 
 
Pharmacovigilance 
Provider: 
Bionical Emas 
Suite 209 
Spirella Building 
Bridge Road 
Letchworth Garden City 
Hertfordshire SG6 4ET, UK 
Tel: 
 
Central Laboratory: 
The Doctors Laboratory 
The Halo Building 
1 Mabledon Place 
London WC1H 9AX, UK 
Tel: 
 
Bioanalytical 
Laboratory: 
PPD, Inc. (Part of Thermo Fischer Scientific) 
5516 Falmouth Street, Suite 301 ABC 
Richmond, VA 23230, USA 
Tel: 
 

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1 Table of Contents  
1 
Table of Contents ............................................................................................ 5 
2 
List of Tables and Figures ............................................................................... 9 
2.1 
Table of In-Text Tables ...................................................................... 9 
2.2 
Table of In-Text Figures ..................................................................... 9 
3 
Synopsis ....................................................................................................... 10 
4 
List of Abbreviations ...................................................................................... 15 
5 
Background Information ................................................................................ 17 
5.1 
Introduction ...................................................................................... 17 
5.2 
Investigational Medicinal Products ................................................... 17 
5.3 
Previous Study Findings .................................................................. 18 
 
Non-clinical Findings ....................................................................... 18 
 
Clinical Findings .............................................................................. 19 
6 
Rationale ....................................................................................................... 20 
6.1 
Study Rationale ............................................................................... 20 
6.2 
Dose Rationale ................................................................................ 21 
6.3 
Population Rationale ....................................................................... 21 
6.4 
Risks and Benefits ........................................................................... 22 
 
Risks Associated with Delafloxacin Administration .......................... 22 
 
COVID-19 Related Risks and Risk Mitigation Measures .................. 23 
 
General Risks and Overall Risk-Benefit Assessment ....................... 24 
7 
Objectives and Endpoints .............................................................................. 24 
8 
Study Design ................................................................................................. 24 
8.1 
Study Plan ....................................................................................... 24 
8.2 
Criteria for In-Study Decisions ......................................................... 27 
 
Decision Points ................................................................................ 27 
 
Criteria for Dose Level and Prandial Status Selection ...................... 27 
8.3 
Subject Withdrawal .......................................................................... 28 
8.4 
Subject Replacement ...................................................................... 29 
8.5 
Stopping Criteria .............................................................................. 29 
8.6 
Study Termination ........................................................................... 29 
8.7 
Lost to Follow-up ............................................................................. 30 
8.8 
Treatment Assignment and Randomisation ..................................... 30 
 
Subject Numbers ............................................................................. 30 
 
Blinding ........................................................................................... 31 
9 
Selection of Subjects ..................................................................................... 31 
9.1 
Informed Consent ............................................................................ 31 
9.2 
Inclusion Criteria .............................................................................. 31 
9.3 
Exclusion Criteria ............................................................................. 32 
9.4 
Contraception and Restrictions ........................................................ 33 
 
Sperm Donation............................................................................... 35 

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Egg Donation ................................................................................... 35 
9.5 
Pregnancy ....................................................................................... 35 
9.6 
Additional Study Restrictions ........................................................... 35 
10 
Study Procedures .......................................................................................... 36 
10.1 
Screening ........................................................................................ 36 
 
Subject Re-Screening ...................................................................... 36 
10.2 
Admission and Pre-dose Procedures ............................................... 36 
10.3 
Study Day Procedures ..................................................................... 37 
 
Blood Volume .................................................................................. 37 
 
Timing of Procedures ...................................................................... 37 
 
Discharge from the Clinical Unit ....................................................... 37 
 
Medical Supervision ........................................................................ 38 
 
Follow-up ......................................................................................... 38 
11 
Dosing of Subjects ........................................................................................ 38 
11.1 
Food and Fluid Intake ...................................................................... 38 
11.2 
Administration of Test Preparations ................................................. 39 
11.3 
Dosing Compliance ......................................................................... 40 
11.4 
Prior and Concomitant Medications ................................................. 40 
12 
Assessment of Efficacy ................................................................................. 40 
13 
Assessment 
of 
Pharmacokinetics, 
Taste/Palatability 
and 
Pharmacodynamics ....................................................................................... 40 
13.1 
Assessment of Pharmacokinetics .................................................... 40 
 
Pharmacokinetic Blood Sampling .................................................... 40 
13.2 
Assessment of Pharmacodynamics ................................................. 41 
13.3 
Taste/Palatability Evaluation ............................................................ 41 
14 
Assessment of Safety ................................................................................... 42 
14.1 
Definition and Classification of Adverse Events ............................... 42 
14.2 
Assessment of Causality ................................................................. 42 
14.3 
Recording Adverse Events .............................................................. 43 
14.4 
Serious Adverse Events .................................................................. 43 
 
Definition of Serious Adverse Events ............................................... 43 
 
Definition of Suspected Unexpected Serious Adverse 
Reactions ........................................................................................ 43 
14.5 
Laboratory Measurements ............................................................... 43 
 
Haematology and Clinical Chemistry ............................................... 44 
 
Virology ........................................................................................... 44 
 
Urinalysis ......................................................................................... 44 
 
Pregnancy Test ............................................................................... 44 
 
Follicle-Stimulating Hormone Test ................................................... 44 
 
Drug Screen .................................................................................... 45 
 
Alcohol Breath Test ......................................................................... 45 
 
Carbon Monoxide Breath Test ......................................................... 45 
 
SARS-CoV-2 Tests (If Required) ..................................................... 45 
 Abnormal Laboratory Findings ......................................................... 45 
14.6 
Vital Signs Measurements ............................................................... 46 

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14.7 
ECG Measurements ........................................................................ 46 
14.8 
Body Weight, Height and BMI .......................................................... 46 
14.9 
Physical Examination ...................................................................... 46 
14.10 
Additional Safety Procedures........................................................... 47 
15 
Statistics and Data Analysis .......................................................................... 47 
15.1 
Sample Size Justification ................................................................. 47 
15.2 
Data Management ........................................................................... 47 
15.3 
Pharmacokinetic Data Analysis ....................................................... 47 
15.4 
Statistical Data Analysis .................................................................. 48 
15.5 
Interim Analysis ............................................................................... 49 
16 
Safety Reporting to Regulatory Authorities and Ethics Committees............... 49 
16.1 
Events Requiring Expedited Reporting ............................................ 49 
16.2 
Urgent Safety Measures .................................................................. 50 
16.3 
Reporting ......................................................................................... 50 
 
Reporting Serious Adverse Events .................................................. 50 
 
Reporting of Suspected Unexpected Serious Adverse 
Reactions ........................................................................................ 50 
 
Expedited Reporting of Events ........................................................ 51 
 
Reporting of Urgent Safety Measures .............................................. 51 
 
Reporting of COVID-19 Vaccine-Related Adverse Events ............... 51 
16.4 
Serious Breaches ............................................................................ 51 
17 
Protocol Amendments and Deviations ........................................................... 51 
17.1 
Amendments ................................................................................... 51 
17.2 
Protocol Deviations .......................................................................... 52 
18 
Regulatory ..................................................................................................... 52 
18.1 
Compliance ..................................................................................... 52 
18.2 
MHRA and Ethical Approval ............................................................ 52 
18.3 
Source Data .................................................................................... 52 
18.4 
Declaration of the End of the Study ................................................. 53 
18.5 
Document Storage and Archiving .................................................... 53 
18.6 
Protection of Personal Data and Confidentiality ............................... 53 
18.7 
Data Security Breach ....................................................................... 54 
19 
Quality Control and Quality Assurance .......................................................... 54 
19.1 
Monitoring........................................................................................ 54 
20 
Finance and Insurance .................................................................................. 55 
21 
Publication .................................................................................................... 55 
22 
References .................................................................................................... 55 
Appendix 1 
Clinical Laboratory Parameters ........................................................ 57 
Appendix 2 
Schedule of Assessments ............................................................... 58 

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Appendix 3 
Example Taste/Palatability Questionnaire ....................................... 60 
Appendix 4 
Breakfast Content ............................................................................ 61 
Appendix 5 
Protocol Amendment Summary of Changes .................................... 62 
 

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2 List of Tables and Figures  
2.1 
Table of In-Text Tables  
Table 1 
Investigational Medicinal Products ............................................................ 18 
Table 2 
Description of Regimens ........................................................................... 25 
Table 3 
Plasma Pharmacokinetic Parameters ....................................................... 48 
 
2.2 
Table of In-Text Figures  
Figure 1 
Study Sequence ....................................................................................... 27 
 
 

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3 Synopsis  
 
Sponsor: 
Melinta Therapeutics, LLC 
Drug Substance: 
Baxdela® (delafloxacin) 
IRAS ID: 
1009679 
Title of Study: 
A Phase 1, Single Part, Partially Randomised, Open-Label Study to Evaluate the 
Relative Bioavailability of a Taste-Masked Delafloxacin Powder for Oral Suspension with 
Oral Delafloxacin Tablet Reference in Healthy Subjects 
Principal Investigator: 
 
Study Centre: 
Quotient Sciences, Mere Way, Ruddington Fields, Ruddington, Nottingham, NG11 6JS, 
UK 
Objectives and Endpoints: 
Objectives 
Endpoints 
Primary 
 
To determine the relative bioavailability of 
delafloxacin 
Powder 
for 
Oral 
Suspension 
compared to that of oral delafloxacin Tablet 
reference 
 
Results of the formal statistical analysis of overall 
exposure (AUC) for delafloxacin Powder for Oral 
Suspension, compared to oral delafloxacin Tablet 
reference 
Secondary 
To determine the PK of delafloxacin Powder for 
Oral Suspension formulation 
 
PK parameters for delafloxacin: Tlag, Tmax, 
Cmax, AUC(0-24), AUC(0-last), AUC(0-inf), 
lambda-z, Frel,T1/2, CL/F, Vz/F, and MRT, as 
applicable 
To determine the relative bioavailability of 
delafloxacin Powder for Oral Suspension in the 
fed and fasted state 
Results of the formal statistical analysis of overall 
exposure (AUC) for delafloxacin Powder for Oral 
Suspension in the fed state compared to the 
fasted state 
To provide additional safety and tolerability 
information for orally administered delafloxacin 
Assessment of adverse events (AEs), vital signs, 
electrocardiograms (ECGs), physical 
examinations, and clinical laboratory tests 
Exploratory 
To evaluate the taste/palatability attributes (smell, 
sweetness, bitterness, flavour, mouthfeel/texture, 
grittiness, and aftertaste) and overall acceptability 
of delafloxacin Powder for Oral Suspension 
 
Results of the taste questionnaire 
Methodology: 
This is a Phase 1, single centre, single part, partially randomised, open-label, relative 
bioavailability study in healthy subjects. 
It is planned to enrol approximately 16 healthy male and healthy non-pregnant, 
non-lactating female subjects.  

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It is planned to administer up to four regimens:  
Period 
Regimen 
Investigational Medicinal Product 
Dose 
Route of 
Administration 
1 and 2 
A 
delafloxacin Tablet (reference) 
450 mg 
Oral, Fasted 
B 
delafloxacin Powder for Oral Suspension, 
reconstituted with orange flavoured vehicle 
450 mg 
Oral, Fasted 
3 
C 
delafloxacin Powder for Oral Suspension, 
reconstituted with orange flavoured vehicle 
450 mg 
or 
XX mg 
Oral, Fed 
or 
Oral, Fasted 
4 (optional) 
D 
delafloxacin Powder for Oral Suspension, 
reconstituted with orange flavoured vehicle 
XX mg 
or 
YY mg 
Oral, Fed 
or 
Oral, Fasted 
The order in which regimens are dosed may be subject to change due to logistical reasons 
The effect of food on the PK of a novel delafloxacin Powder for Oral Suspension 
formulation may be explored in Period 3 or optional Period 4, by administering 
investigational medicinal product (IMP) after a high-fat breakfast. The effect of increasing 
or decreasing the dose level may also be explored. 
There will be an interim decision meeting after Periods 2 and 3 to review the PK and 
safety data for up to 48 hours post-dose from preceding periods, in order to determine 
the dose and prandial state for Regimen C and Regimen D (if applicable).  
There will be a minimum washout of 4 days between dosing in Periods 1 and 2. The 
intervals between Periods 2 and 3, and Period 3 and optional Period 4, will require a 
minimum of 14 days, to permit the interim decision process and IMP manufactures. 
Study Design: 
Subjects will undergo preliminary screening procedures for the study at the screening 
visit (Day -28 to Day -2).  
Periods 1 and 2 
Subjects will be admitted in the morning on the day before dosing (Day -1) in Period 1. 
Subjects will receive a snack in the evening, after which they will fast overnight from all 
food and drink (except water) for a minimum of 10 hours. Subjects will be administered 
IMP on the morning of Day 1 in the fasted state. Subjects will complete a written 
taste/palatability questionnaire individually and privately following IMP administration 
(Regimen B only). 
Subjects will be randomised in a 1:1 ratio to one of two sequences (AB or BA) 
immediately prior to dosing in Period 1, for allocation of regimens across Periods 1 and 2. 
Blood and urine samples will be collected at regular intervals for PK and safety analysis, 
as applicable, from admission until 48 hours post-dose during each period. Subjects will 
remain resident in the clinical unit during the washout period (minimum 4 days) between 
Periods 1 and 2. Subjects will be discharged from the clinical unit at 48 hours post-dose 
(Day 3) in Period 2.  
Following dosing of Regimens A and B, there will be an interim decision meeting to 
review available PK and safety data to decide the dose level and prandial state for 
Regimen C. The Investigator and Sponsor will decide whether to continue to evaluate a 
450 mg dose level of delafloxacin Powder for Oral Suspension following a high-fat 
breakfast, or to evaluate an alternative dose level in the fasted state.  
Period 3 
Subjects will be admitted in the evening on the day before dosing (Day -1). Subjects will 
fast overnight from all food and drink (except water) for a minimum of 10 hours, and will 

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be administered IMP on the morning of Day 1 in the fasted state (if a different dose level 
is selected), or approximately 30 minutes after a high-fat breakfast (if a change to 
prandial state is selected). Subjects will complete a written taste/palatability 
questionnaire individually and privately following IMP administration. 
Blood and urine samples will be collected at regular intervals for PK and safety analysis, 
as applicable, from admission until 48 hours post-dose (Day 3), at which time subjects 
will be discharged from the clinical unit.  
Following dosing of Regimen C, there will be an interim decision meeting to review 
available PK and safety data, to decide whether to proceed with optional Period 4 or 
whether to end the study. If it is decided to end the study, a follow-up phone call will take 
place on Day 6 ± 1 to ensure the ongoing wellbeing of subjects. If a subject reports any 
AEs that present a cause for concern, they will be required to attend the clinical unit for 
an (unscheduled) follow-up visit. End of study is defined as completion of the last 
follow-up phone call or unscheduled follow-up visit. If it is decided to proceed with 
optional Period 4, the dose level and prandial state for Regimen D will be determined; 
the Investigator and Sponsor will decide whether to continue to evaluate the dose level 
selected for Regimen C following a high-fat breakfast, or to evaluate an alternative dose 
level in the fasted state.  
Optional Period 4 
Subjects will be admitted in the evening on the day before dosing (Day -1). Subjects will 
fast overnight from all food and drink (except water) for a minimum of 10 hours, and may 
be administered IMP on the morning of Day 1 in the fasted state (if a different dose level 
is selected), or approximately 30 minutes after a high-fat breakfast (if a change to 
prandial state is selected). Subjects will complete a written taste/palatability 
questionnaire individually and privately following IMP administration. 
Blood and urine samples will be collected at regular intervals for PK and safety analysis, 
as applicable, from admission until 48 hours post-dose (Day 3), at which time subjects 
will be discharged from the clinical unit. A follow-up phone call will take place on 
Day 6 ± 1 to ensure the ongoing wellbeing of subjects. If a subject reports any AEs that 
present a cause for concern, they will be required to attend the clinical unit for an 
(unscheduled) follow-up visit; completion of the last follow-up phone call or unscheduled 
follow-up visit will be considered the end of the study. 
Number of Subjects Planned: 
The study is exploratory, and no formal sample size calculation has been made. Based 
on experience from previous studies of a similar design, a sample size of 16 subjects 
and a minimum of 12 evaluable subjects is considered sufficient to meet the objectives 
of the study. 
An evaluable subject for the relative bioavailability assessment will have received 
delafloxacin Powder for Oral Suspension (test) and the oral delafloxacin Tablet 
(reference) at the same dose level, in the fasted state, and have evaluable PK and safety 
data to 48 hours post-dose. 
An evaluable subject for the food effect assessment will have received delafloxacin 
Powder for Oral Suspension in the fed and fasted state, at the same dose level, and 
have evaluable PK and safety data to 48 hours post-dose. 
Subjects withdrawn due to an IMP-related AE will not be replaced.  
Subjects who are withdrawn for other reasons may be replaced as required, by 
agreement between the Investigator and the Sponsor, to ensure sufficient evaluable 
subjects. Up to 4 replacement subjects may be enrolled into the study. The maximum 
number of subjects that may be dosed is 20. 

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Duration of Study: 
Subjects will receive single administrations of delafloxacin on up to 4 separate occasions. 
The estimated time from screening until the follow-up phone call is approximately 
14 weeks. 
Investigational Medicinal Product, Dose and Mode of Administration: 
The following IMPs will be used in this clinical study: 
IMP Name 
Dose 
Route of Administration 
delafloxacin Tablet, 450 mg (reference) 
450 mga 
Oral, Fasted 
delafloxacin Powder for Oral Suspension,  
300 – 600 mgb 
300 mg – 600 mgc 
Oral, Fasted or Fed 
a Each oral delafloxacin Tablet contains 649.35 mg delafloxacin meglumine (salt form) equivalent of 450 mg 
free acid 
b Delafloxacin Powder for Oral Suspension will be reconstituted with orange flavoured vehicle 
c Delafloxacin Powder for Oral Suspension contains 439.5 mg to 878.9 mg delafloxacin meglumine (salt 
form) equivalent to 300 mg to 600 mg free form 
Oral tablets will be administered with a total of 240 mL of water. If required, additional 
water may be given with the IMP in 50 mL aliquots. 
Immediately after administration of delafloxacin Powder for Oral Suspension, the dosing 
vessel will be rinsed with water and subjects will consume the rinse solution. Subjects 
will then consume further water to a total volume of 240 mL (including the dosing volume 
and volume used to rinse the dosing vessel). If required, additional water may be given 
with the IMP in 50 mL aliquots. 
Study Assessments: 
The following blood and urine samples will be collected, and assessments performed, at 
specified time points: 
• 
Delafloxacin in plasma for PK analysis. 
• 
Taste/palatability questionnaire (following delafloxacin Powder for Oral Suspension 
[i.e., test] regimens only). 
• 
Safety assessments comprising AE monitoring, clinical laboratory tests (clinical 
chemistry, haematology and urinalysis), physical examinations, single 12-lead ECGs 
and vital signs. 
Statistical Analysis: 
PK parameters will be calculated using standard non-compartmental analysis to obtain 
at a minimum: Tlag, Tmax, Cmax, AUC(0-24), AUC(0-last), AUC(0-inf), Lambda-z, Frel, 
T1/2, CL/F, Vz/F, and MRT for delafloxacin in plasma, as applicable.  
Descriptive summaries for all PK, safety, and taste data by regimen, as applicable, will 
be provided (including changes from baseline as required). 
Formal statistical analysis will be performed on the PK parameters Cmax, AUC(0-last), 
and AUC(0-inf) to assess relative bioavailability. The PK parameters will undergo a 
natural logarithmic transformation and will be analysed using a mixed effect model, with 
terms for sequence and regimen as fixed effects, and subject within sequence as a 
random effect.  
Formal statistical analysis will also be performed on the PK parameters Cmax, 
AUC(0-last), and AUC(0-inf) to assess for the effects of food on delafloxacin Powder for 
Oral Suspension regimens administered at the same dose level. The PK parameters will 
undergo a natural logarithmic transformation and will be analysed using a mixed effect 
model, with terms for regimen as fixed effect, and subject as a random effect.  
Additionally, formal statistical analysis may be performed on the log-transformed, 
dose-corrected PK parameters Cmax, AUC(0-last), and AUC(0-inf) to assess dose 

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proportionality, if two dose levels of delafloxacin Powder for Oral Suspension are 
administered in the same prandial state, using a mixed effect model, with terms for 
regimen as a fixed effect and subject as a random effect.  
 

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4 List of Abbreviations 
Abbreviation 
Definition 
ABSSSI 
acute bacterial skin and skin structure infections 
ADR 
adverse drug reaction 
AE 
adverse event 
ALT 
alanine aminotransferase 
BID 
twice daily 
BMI 
body mass index 
CABP 
community acquired bacterial pneumonia 
CHMP 
Committee for Medicinal Products for Human Use 
CI 
confidence interval 
CNS 
central nervous system 
COVID-19 
Coronavirus Disease 2019 
CSPM 
Clinical Sample Processing Manual 
CV% 
coefficient of variation 
CYP 
cytochrome P450 
DMP 
data management plan 
EC 
ethics committee 
ECG 
electrocardiogram 
eCRF 
electronic case report form 
EMA 
European Medicines Agency  
FDA 
US Food and Drug Administration 
FSH 
follicle stimulating hormone 
GCP 
Good Clinical Practice 
GI 
gastrointestinal 
GMR 
geometric mean ratios 
HBsAg 
hepatitis B surface antigen 
HCV Ab 
hepatitis C virus antibody 
HIV 
human immunodeficiency virus 
HRT 
hormone replacement therapy 
IB 
Investigator’s Brochure 
ICF 
informed consent form 
ICH 
International Council for Harmonisation of Technical 
Requirements for Pharmaceuticals for Human Use 
IMP 
investigational medicinal product 
ISF 
Investigator Site File 

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IV 
intravenous 
MRSA 
methicillin resistant Staphylococcus aureus 
MHRA 
Medicines and Healthcare products Regulatory Agency 
PIS 
Participant Information Sheet 
PK 
pharmacokinetic(s) 
QA 
quality assurance 
QC 
quality control 
QTc 
corrected QT interval 
QTcF 
corrected QT interval by Fridericia’s formula 
RAP 
Reporting and Analysis Plan 
SAC 
safety advisory committee 
SAE 
serious adverse event 
SAR 
serious adverse reaction 
SARS-CoV-2 
severe acute respiratory syndrome coronavirus 2 
SOP 
standard operating procedure 
SUSAR 
suspected unexpected serious adverse reaction 
TEAE 
treatment-emergent adverse event 
The pharmacokinetic definitions used in this study are presented in Section 15.3. 
 

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5 Background Information  
5.1 
Introduction  
Delafloxacin (also noted as RX-3341, ABT-492, ABT-319492, or WQ-3034, and currently 
marketed in multiple countries, including in the US as Baxdela® [1], and in the EU as 
Quofenix® [2]) is an approved, broad-spectrum anionic fluoroquinolone antibiotic for the 
treatment of adults with acute bacterial skin and skin structure infections (ABSSSI) and 
community-acquired bacterial pneumonia (CABP). Melinta Therapeutics, LLC (Melinta; 
formerly Rib-X Pharmaceuticals) licensed Baxdela® from Wakunaga Pharmaceutical 
Company in Japan. Prior to its licensing by Melinta, the compound was developed by 
Abbott Laboratories as an oral formulation (ABT-492) for use in the treatment of 
community-acquired infections. 
Throughout the world, the incidence of antimicrobial resistance has increased for 
bacterial infections in hospital and community settings. Staphylococcus aureus, 
especially methicillin resistant S. aureus (MRSA), ranks as the most frequently isolated 
pathogen in hospital intensive care units in the US. The Centers for Disease Control and 
Prevention estimates that MRSA is responsible for more than 300,000 infections, 
resulting in more than 10000 deaths per year in the US [3]. The risk factors for MRSA 
are constantly evolving, and the distinction between community-acquired MRSA and 
hospital-acquired MRSA is becoming less clear from a therapeutic standpoint because 
of overlapping susceptibility patterns. 
Whilst gram-positive pathogens, including streptococci and staphylococci, are the most 
common bacteria associated with ABSSSI, gram-negative pathogens must also be 
considered as causative when selecting initial empiric therapy, particularly in patients 
with certain comorbid conditions such as diabetes, surgical site infections, anal and 
perianal region infections, and compromised vascular perfusion [4]. Drug-resistant 
bacteria are demonstrating alarming trends as causative pathogens in skin and soft 
tissue infections. Delafloxacin exhibits a concentration-dependent bactericidal activity 
against gram-positive and gram-negative bacteria in vitro [1]. 
Baxdela® is indicated in adults for the treatment of ABSSSIs and CABP, and can be 
administered as an intravenous (IV) infusion or as an oral tablet [1]. Melinta is developing 
an oral suspension formulation as a potential therapeutic for CABP in paediatric patients 
(target age group 2 months to 18 years). Safety and effectiveness in paediatric patients 
below the age of 18 years have not been established [5]. 
This study will evaluate the relative bioavailability of a novel powder for oral suspension 
formulation of Baxdela®, intended for weight-based paediatric dosing, relative to that of 
the licensed Baxdela® oral tablet, in approximately 16 healthy adults. Food effect and 
effect of a change in dose level on bioavailability of the novel powder for oral suspension 
will also be evaluated. 
5.2 
Investigational Medicinal Products  
The investigational medicinal products (IMPs) that will be used in this clinical study are 
presented in Table 1. 

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Table 1 
Investigational Medicinal Products  
IMP Name 
Dose 
Route of Administration 
delafloxacin Tablet, 450 mg (reference) 
450 mga 
Oral, Fasted 
delafloxacin Powder for Oral Suspension,  
300 – 600 mgb 
300 mg – 600 mgc 
Oral, Fasted or Fed 
a Each oral delafloxacin Tablet contains 649.35 mg delafloxacin meglumine (salt form) equivalent of 450 mg 
free acid 
b Delafloxacin Powder for Oral Suspension will be reconstituted with orange flavoured vehicle 
c Delafloxacin Powder for Oral Suspension contains 439.5 mg to 878.9 mg delafloxacin meglumine (salt 
form) equivalent to 300 mg to 600 mg free form 
Delafloxacin Powder for Oral Suspension is an un-licensed medicinal product for use 
only in the proposed clinical trial. 
The oral delafloxacin Tablets to be used in this study are marketed in the US (as 
Baxdela®). They are to be used in the clinical trial within the terms of the marketing 
authorisation, other than being administered to healthy volunteers. 
Only subjects enrolled in the study may receive study treatment and only authorised site 
staff may supply or administer study treatment. All study treatments will be stored in a 
secure, environmentally-controlled, and monitored (manual or automated) area in 
accordance with the labelled storage conditions with access limited to the Investigator 
and authorised site staff. 
Where Quotient Sciences is manufacturing the IMPs, suitability of the manufacturing 
process will be documented in a Pharmaceutical Development and Control Strategy 
Report. 
IMPs will be reconciled and destroyed in accordance with the study-specific quality 
agreement and technical addendum. 
5.3 
Previous Study Findings  
Full details of previous study findings can be found in the Investigator’s Brochure (IB) [5]. 
A summary of the non-clinical and clinical findings is provided below. 
 Non-clinical Findings  
Delafloxacin was demonstrated to have a favourable pharmacokinetic (PK) profile in 
non-clinical studies, with rapid absorption from the gastrointestinal (GI) tract following 
oral administration, and extensive distribution into tissues, but with essentially no 
retention of drug in tissues. The absorption, distribution, metabolism, and excretion study 
program demonstrated the rat and dog to be acceptable models for studying the 
non-clinical safety of delafloxacin. 
The non-clinical safety assessment of delafloxacin comprised studies of oral and IV 
acute and repeat-dose toxicology in mice (single dose only), rats, and dogs, and in vitro 
and in vivo genotoxicity tests and reproductive and developmental toxicity in rats and 
rabbits. Genotoxicity tests demonstrated a favourable safety margin for clastogenicity in 
vivo, and a single positive clastogenic finding in vitro. In addition, other evaluations were 
conducted to evaluate dose formulations and local tolerance and to qualify impurities. 
The order and timing of studies followed appropriate guidelines and regulatory feedback 
to allow testing in humans, including women of childbearing potential. Registration 
non-clinical studies of up to 3 months duration support the clinical treatment duration of 

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12-hour intervals (i.e., twice daily [BID]) for 5 to 14 days. Primary findings were related 
to GI effects and included abnormal stool, dilated caecum, decreased food consumption 
and/or body weights in rats, and emesis, salivation, and abnormal stool/diarrhoea in 
dogs. Additionally, in dog studies of ≥4-weeks duration, elevations in liver serum 
enzymes (primarily alanine aminotransferase [ALT] and alkaline phosphatase) without 
microscopic changes were seen in some dogs. Toxicokinetic measurements were done 
extensively throughout the programme. Designs for pivotal studies complied with US 
Food and Drug Administration (FDA) Good Laboratory Practice and International Council 
for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) 
guidelines applicable at the time the studies were conducted. 
The primary pharmacology of delafloxacin has been studied in vitro and in vivo with 
established models to define antimicrobial effects. Delafloxacin was demonstrated to 
have a favourable PK profile in non-clinical studies, with rapid absorption and extensive 
distribution into tissues, but with essentially no retention of drug in tissues. The 
non-clinical pharmacology results with delafloxacin support the use of this drug for the 
treatment of ABSSSI and other indications. 
An extensive core battery of central nervous system (CNS), cardiovascular, and 
respiratory evaluations was conducted with delafloxacin, including supplemental GI 
evaluations. These studies did not indicate a risk to human safety, with most effects 
restricted to high doses/concentrations, associated with delafloxacin plasma 
concentrations exceeding those observed in clinical studies. 
Further details of the non-clinical studies conducted can be found in the IB for 
delafloxacin [5].  
 Clinical Findings  
Delafloxacin is a broad-spectrum anionic fluoroquinolone antibiotic, approved for 
administration in adults as IV infusion and oral tablet formulations, and has been 
marketed for the treatment of adults with ABSSSI and CABP as Baxdela® [1] since 2017 
and 2019, respectively, in the US, and as Quofenix® [2] since 2019 and 2021, 
respectively, in the EU. A total of 32 clinical studies have been completed with oral and 
IV delafloxacin, including twenty-four Phase 1, four Phase 2 and four Phase 3 studies. 
In total, approximately 3117 subjects and patients have received delafloxacin in 
completed trials. 
Following oral tablet administration, peak plasma concentrations of delafloxacin occur at 
a median of 0.8 hours (range 0.5 hours to 4 hours). Delafloxacin maximum mean plasma 
concentration measured after dosing (Cmax) and area under the mean concentration 
time curve (AUC) increase proportionally to dose over the range of 50 mg to 1600 mg 
and 200 mg to 1600 mg, respectively. The absolute bioavailability of oral delafloxacin 
Tablet is 58.8%. The administration of delafloxacin with food delays absorption and 
reduces Cmax, but does not alter total absorption (AUC). Thus, delafloxacin can be given 
without regard to food. The 450 mg delafloxacin commercial tablet and 300 mg IV 
Captisol® lyophilised formulations are bioequivalent with regard to total exposure (AUC). 
Multiple oral BID dosing of delafloxacin 450 mg tablets to steady-state results in 1.35-fold 
higher concentrations of delafloxacin. Delafloxacin is well distributed after IV and oral 
tablet administration, with a mean volume of distribution at steady state of 34.2 L, which 
is just below total body water (42 L). Plasma protein binding is approximately 84%.  

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Delafloxacin is primarily metabolised by glucuronidation, with oxidative metabolism 
representing <1% of the dose. The glucuronidation of delafloxacin is primarily mediated 
by UGT1A1 and UGT1A3. Unchanged parent drug is the predominant component in 
plasma; no single metabolite represents ≥ 20% of circulating components. Delafloxacin 
is eliminated primarily by renal excretion, but biliary clearance and transintestinal 
elimination may also play a role. Metabolism accounts for about 20% of the elimination 
of delafloxacin. 
Ten Phase 1 studies have been conducted examining the safety, tolerability, and PK of 
various oral formulations in single and multiple doses over a range of 50 mg to 1600 mg. 
The treatment-emergent adverse events (TEAEs) experienced by ≥2% of the subjects in 
the oral Phase 1 studies were mostly GI related, including diarrhoea (13.5%), headache 
(8.7%), nausea (5.2%), and abdominal pain (2.8%). These were also the most frequently 
occurring (≥2%) TEAEs with possible, probable, or definite relatedness to delafloxacin 
(diarrhoea [12.3%], headache [5%], nausea [4.2%], and abdominal pain [2.8%]). There 
were no serious adverse events (SAEs) in these trials. Aggregate data suggest a dose 
response, with a greater frequency and severity of diarrhoea at higher dose levels.  
Electrocardiogram (ECG) tracings were routinely collected in all clinical trials conducted; 
no remarkable effects were noted, and delafloxacin has shown minimal potential to 
cause corrected QT interval (QTc) prolongation after once daily oral administration at 
doses of 200 mg, 800 mg, and 1200 mg.  
Delafloxacin does not inhibit cytochrome P450 (CYP) enzymes or transporters to any 
significant degree. In vitro, delafloxacin has been shown to be a mild inducer of CYP3A4; 
however, an in vivo clinical drug-drug interaction study demonstrated no interactions with 
midazolam, a sensitive CYP3A4 substrate. Hence, clinically significant drug-drug 
interactions due to inhibition of CYP-mediated biotransformation of co-administered 
drugs by delafloxacin are unlikely in humans. 
Delafloxacin, at 200 mg/day and 400 mg/day for 6 days, did not demonstrate clinically 
significant phototoxic potential at any wavelengths tested (295 nm to 430 nm). In 
particular, the classical pattern of fluoroquinolone phototoxicity as detected in previous 
phototoxicity studies (i.e., a UVA phenomenon maximal at 24 hours) was not seen. 
6 Rationale  
6.1 
Study Rationale  
This study will evaluate the relative bioavailability of a novel powder for oral suspension 
formulation of Baxdela® (delafloxacin), intended for weight-based paediatric dosing to 
treat CABP, relative to that of the licensed Baxdela® (delafloxacin) oral tablet, in 
approximately 16 healthy adults. The novel delafloxacin Powder for Oral Suspension in 
this study will be reconstituted with a sweetened, flavoured vehicle, selected from a 
previous basic science study (assessing the taste of an oral suspension with vehicles 
containing 
different 
sweeteners 
and 
sweetener/flavour 
combinations), 
which 
demonstrated the most promising taste/palatability profile. 
A Phase 1 study exploring food effect of a 900 mg oral delafloxacin tablet administered 
after a 10 hour fast, or after a high-fat meal, demonstrated no clinically significant food 
effect [5]. It is planned to explore food effect in this study to determine whether there is 
a food effect on bioavailability of the novel delafloxacin Powder for Oral Suspension 
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As PK and relative bioavailability of a novel formulation of delafloxacin Powder for Oral 
Suspension compared with the oral delafloxacin Tablet (reference) will be assessed, the 
study will be open-label.  
Randomisation will be used in Periods 1 and 2 to minimise bias in the assignment of 
subjects to regimens, to increase the likelihood that known and unknown subject 
attributes (e.g., demographic and baseline characteristics) are evenly balanced across 
regimens, and to enhance the validity of comparisons. As a single formulation/unit dose 
will be administered in Period 3 and optional Period 4, no randomisation is required for 
these periods.  
6.2 
Dose Rationale  
Oral delafloxacin is currently licensed for use at a dose of 450 mg BID [1]. Therefore, a 
single 450 mg dose has been selected for the relative bioavailability assessment in 
Periods 1 and 2.  
Single oral doses of up to 1600 mg and multiple oral doses of up to 1200 mg have been 
safely administered to healthy volunteers in previous Phase 1 clinical trials. Single oral 
doses of delafloxacin Powder for Oral Suspension administered to healthy subjects in 
either the fasted or fed state will not exceed the highest dose previously administered in 
healthy subjects (1600 mg), are expected to be safe and well tolerated, and will allow for 
the development of a dosing regimen for this prototype formulation with similar exposure 
to the 450 mg oral delafloxacin Tablet (reference) formulation. A food effect study has 
been conducted using the 900 mg oral delafloxacin Tablet formulation, and the results 
indicated no clinically significant food effect.  
6.3 
Population Rationale  
As this is a Phase 1 study assessing the PK, relative bioavailability, safety, and taste of 
delafloxacin, the most relevant population is healthy volunteers, as recommended by the 
US FDA [6] and the European Medicines Agency (EMA) [7]. Subjects who are 
non-smokers without a history of alcohol or drug abuse or regular co-medication (except 
hormonal contraception and hormone replacement therapy [HRT]) are proposed to avoid 
interaction on drug metabolism and to avoid non-compliance.  
Oral delafloxacin Tablet is currently licensed for use in both males and females [1]. 
Additionally, delafloxacin did not affect the fertility of male and female rats up to the 
highest IV dose tested (120 mg/kg/day) [8], which is approximately 5-fold the estimated 
human plasma exposure based on AUC. In embryo-foetal studies in rats and rabbits, 
orally administered delafloxacin demonstrated no teratogenic effects up to the highest 
doses tested (1600 mg/kg/day and 1.6 mg/kg/day, respectively). There was also no 
evidence of differences in tissue accumulation, distribution, or elimination of delafloxacin 
between repeat orally and intravenously administered delafloxacin in pregnant rats. 
However, the potential for delafloxacin to be excreted in human milk has not been 
studied. Therefore, females of childbearing potential will be allowed to participate in the 
study, as long as they comply with the contraception requirements detailed in 
Section 9.4; male subjects must also comply with these requirements. Additionally, 
pregnant or lactating females, or male subjects with pregnant or lactating female 
partners, will not be permitted take part in the study.  
Based on the above considerations and the target population, healthy male and healthy 
non-pregnant, non-lactating female subjects aged 18 to 55 years, inclusive, are 
considered suitable for this study. 

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6.4 
Risks and Benefits  
 Risks Associated with Delafloxacin Administration  
Delafloxacin is a fluoroquinolone; this class of antibacterial drugs have been associated 
with disabling and potentially irreversible serious adverse reactions (SARs) from different 
body systems that can occur together in the same patient. Commonly seen adverse 
reactions to fluroquinolones include tendinitis, tendon rupture, arthralgia, myalgia, 
peripheral neuropathy, and CNS effects (hallucinations, anxiety, depression, insomnia, 
severe headaches, and confusion). Serious and occasionally fatal hypersensitivity 
(anaphylactic) reactions have been reported in patients receiving fluoroquinolone 
therapy, including delafloxacin. Clostridium difficile-associated diarrhoea has also been 
reported in users of nearly all systemic antibacterial drugs, including delafloxacin, with 
severity ranging from mild diarrhoea to fatal colitis. Subjects will not be permitted to 
participate in the study if they experience SARs or serious hypersensitivity to any drug 
or formulation excipients, or any previous hypersensitivity to fluoroquinolones, including 
delafloxacin, or if they have acute diarrhoea or constipation in the 7 days before the 
predicted first study day.  
Fluoroquinolones have also been associated with disturbances of blood glucose, 
including symptomatic hyperglycaemia and hypoglycaemia, usually in diabetic patients 
receiving concomitant treatment with an oral hypoglycaemic agent (e.g., glyburide) or 
with insulin. Epidemiologic studies report an increased risk of aortic aneurysm and 
dissection within two months following use of fluoroquinolones, particularly in elderly 
patients. The cause for the increased risk has not been identified; therefore, only healthy 
subjects aged 18 to 55 years, inclusive, will be eligible to take part in the study. 
Unlike some other fluoroquinolones, in pre-clinical studies, delafloxacin does not prolong 
QTc, alter glucose levels, induce convulsions, cause phototoxicity, or lead to microscopic 
changes in the liver, kidney, bone marrow, or eye. Phase 1 clinical trials with delafloxacin 
have also demonstrated no effect on QTc, and no phototoxicity. Compared to other 
fluoroquinolones, the structural attributes of delafloxacin are unique, thereby potentially 
reducing the risk of adverse events (AEs) common to other fluoroquinolones. For 
example, delafloxacin does not bind melanin and was designed structurally to minimise 
the potential for phototoxicity. Delafloxacin has not shown an increase in AEs of special 
interest that have been associated with the quinolone class when compared to non-
quinolone comparators. The safety/general pharmacology and toxicology studies 
support the use of delafloxacin in the clinic and it is approved for the treatment of ABSSSI 
and CABP in patients. However, subjects participating in this study will undergo 
extensive safety assessments to monitor any potential risks associated with 
fluroquinolones, including the following: AE monitoring, physical examinations, vital 
signs, ECGs, and clinical laboratory tests (clinical chemistry, haematology and 
urinalysis). 
Due to its shape and anionic nature, delafloxacin at clinically relevant concentrations 
does not inhibit GABA/N-methyl-D-aspartate and muscarinic receptors, which have been 
associated with CNS events and/or tendinopathies. Therefore, CNS assessments, such 
as the Columbia-Suicide Severity Rating Scale assessment, are not considered 
necessary for this Phase 1 study in healthy subjects.  
Based on clinical trials previously conducted with delafloxacin, the expected adverse 
drug reactions (ADRs) occurring in >2% of subjects are nausea, vomiting, diarrhoea, 
transaminase elevation, and headache. Subjects will be monitored for TEAEs while 
resident in the clinical unit, until the end of the study, and will be treated symptomatically 

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(if required). Any subject experiencing significant increases in transaminases e.g., ALT 
concentration >3 × the upper limit of the reference range, will be withdrawn from further 
dosing (see Section 8.3 for further details).  
The potential effects of delafloxacin on the reproductive capacity of animals has been 
investigated in a number of non-clinical studies; additionally, oral delafloxacin Tablet 
(Baxdela®) is currently licensed for use in males and females [1]. Female subjects of 
childbearing potential who are not pregnant or lactating will be allowed to participate in 
the study, and all subjects will be required to comply with the contraception requirements 
in Section 9.4. 
 COVID-19 Related Risks and Risk Mitigation Measures  
The following risks and risk mitigating measures apply to the time in which the study is 
conducted during the Coronavirus Disease 2019 (COVID-19) pandemic. 
6.4.2.1 IMP Related Risk  
Against the background of the COVID-19 pandemic, the potential risk of a subject 
developing COVID-19 has been considered in terms of the risk-benefit evaluation. The 
mode of action of the IMP – as a fluoroquinolone antibacterial – has been considered 
alongside available pre-clinical and clinical data (including class effects) and it is 
considered that a subject would not be at increased risk of either becoming infected with 
severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2; the virus that causes 
COVID-19) or experiencing a more severe illness. That is, the IMP has no known 
immunomodulatory effect that would confer an increased risk to healthy subjects enrolled 
in the study. 
6.4.2.2 General COVID-19 Related Risk Mitigation Measures  
General risk mitigation against COVID-19 will be implemented in accordance with 
Quotient Sciences’ monitoring and prevention control measures. 
COVID-19 testing may be performed based on current infection rates and availability of 
tests. If required, testing will comprise an antigen test performed at screening and/or on 
Day -1 of each treatment period, prior to admission to the clinical unit, and discharge or 
the day before discharge from each treatment period. Testing time points may be 
changed and additional time points may be added throughout the study as required. The 
decision on COVID-19 testing and the definition of the testing time points are subject to 
change based on the current risk mitigation in place and will be agreed by the study team 
and documented in the Investigator Site File (ISF) via the Clinical Kick-Off Meeting 
minutes or in a file note if the study is ongoing. 
The risk mitigation measures, where applicable, will be amended based on emerging 
government guidance. 
6.4.2.3 COVID-19 Vaccine-Related Risk  
Based on the mechanism of action of the IMP – as a fluoroquinolone antibacterial – there 
is no perceived impact on the safety of the study subjects, or on the study objectives, for 
subjects who may receive these vaccines. It is also very unlikely that administration of 
the IMP would interfere with COVID-19 vaccination response; however, no specific 
pre-clinical or clinical investigations have been conducted at this point with delafloxacin. 
Therefore, subjects will not be permitted to receive a COVID-19 vaccination within 2 days 
(48 hours) prior to admission and for the duration of the study.  

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 General Risks and Overall Risk-Benefit Assessment  
Collecting a blood sample from a vein may cause pain, swelling, bruising, 
light-headedness, fainting, and very rarely, clot formation, nerve damage and/or infection 
at the site of the needle stick. 
During cannulation, more than one attempt may be needed to insert the cannula in a 
vein of a subject and it is possible that bruising and/or inflammation may be experienced 
at the site of cannulation.  
ECG stickers on the subjects' chests and limbs may cause some local irritation and may 
be uncomfortable to remove but subjects will be closely monitored to ensure any local 
irritation does not persist. 
There is no benefit to the subjects from taking part in this study. The development of a 
product to treat CABP in paediatric patients will be of benefit to paediatric patients with 
CABP. 
The overall risk benefit balance is therefore considered to be acceptable. 
7 Objectives and Endpoints  
Objectives 
Endpoints 
Primary 
 
To determine the relative bioavailability of 
delafloxacin 
Powder 
for 
Oral 
Suspension 
compared to that of oral delafloxacin Tablet 
reference 
 
Results of the formal statistical analysis of overall 
exposure (AUC) for delafloxacin Powder for Oral 
Suspension, compared to oral delafloxacin Tablet 
reference 
Secondary 
To determine the PK of delafloxacin Powder for 
Oral Suspension formulation 
 
PK parameters for delafloxacin: Tlag, Tmax, 
Cmax, AUC(0-24), AUC(0-last), AUC(0-inf), 
lambda-z, Frel,T1/2, CL/F, Vz/F, and MRT, as 
applicable 
To determine the relative bioavailability of 
delafloxacin Powder for Oral Suspension in the 
fed and fasted state 
Results of the formal statistical analysis of overall 
exposure (AUC) for delafloxacin Powder for Oral 
Suspension in the fed state compared to the 
fasted state 
To provide additional safety and tolerability 
information for orally administered delafloxacin 
Assessment of AEs, vital signs, ECGs, physical 
examinations, and clinical laboratory tests 
Exploratory 
To evaluate the taste/palatability attributes (smell, 
sweetness, bitterness, flavour, mouthfeel/texture, 
grittiness, and aftertaste) and overall acceptability 
of delafloxacin Powder for Oral Suspension 
 
Results of the taste questionnaire 
8 Study Design  
8.1 
Study Plan  
This is a Phase 1, single centre, single part, partially randomised, open-label, relative 
bioavailability study in healthy subjects. 
It is planned to enrol approximately 16 healthy male and healthy non-pregnant, 
non-lactating female subjects.  
An evaluable subject for the relative bioavailability assessment will have received 
delafloxacin Powder for Oral Suspension (test) and the oral delafloxacin Tablet 

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(reference) at the same dose level, in the fasted state, and have evaluable PK and safety 
data to 48 hours post-dose. 
An evaluable subject for the food effect assessment will have received delafloxacin 
Powder for Oral Suspension in the fed and fasted state, at the same dose level, and 
have evaluable PK and safety data to 48 hours post-dose. 
It is planned to administer up to four regimens (Table 2). 
Table 2 
Description of Regimens  
Period 
Regimen 
Investigational Medicinal Product 
Dose 
Route of 
Administration 
1 and 2 
A 
delafloxacin Tablet (reference) 
450 mg 
Oral, Fasted 
B 
delafloxacin Powder for Oral Suspension, 
reconstituted with orange flavoured vehicle 
450 mg 
Oral, Fasted 
3 
C 
delafloxacin Powder for Oral Suspension, 
reconstituted with orange flavoured vehicle 
450 mg 
or 
XX mg 
Oral, Fed 
or 
Oral, Fasted 
4 (optional) 
D 
delafloxacin Powder for Oral Suspension, 
reconstituted with orange flavoured vehicle 
XX mg 
or 
YY mg 
Oral, Fed 
or 
Oral, Fasted 
Details of the IMPs are provided in Section 5.2. The order in which regimens are dosed may be subject to 
change due to logistical reasons 
The effect of food on the PK of a novel delafloxacin Powder for Oral Suspension 
formulation may be explored in Period 3 or optional Period 4, by administering IMP after 
a high-fat breakfast. The effect of increasing or decreasing the dose level may also be 
explored. 
There will be an interim decision meeting after Periods 2 and 3 to review the PK and 
safety data for up to 48 hours post-dose from preceding periods, in order to determine 
the dose and prandial state for Regimen C and Regimen D (if applicable).  
There will be a minimum washout of 4 days between dosing in Periods 1 and 2. The 
intervals between Periods 2 and 3, and Period 3 and optional Period 4, will require a 
minimum of 14 days, to permit the interim decision process and IMP manufactures. 
The study will follow the design in Figure 1. 
Subjects will undergo preliminary screening procedures for the study at the screening 
visit (Day -28 to Day -2).  
Periods 1 and 2 
Subjects will be admitted in the morning on the day before dosing (Day -1) in Period 1. 
Subjects will receive a snack in the evening, after which they will fast overnight from all 
food and drink (except water) for a minimum of 10 hours. Subjects will be administered 
IMP on the morning of Day 1 in the fasted state. Subjects will complete a written 
taste/palatability questionnaire individually and privately following IMP administration 
(Regimen B only). 
Subjects will be randomised in a 1:1 ratio to one of two sequences (AB or BA) 
immediately prior to dosing in Period 1, for allocation of regimens across Periods 1 and 2. 

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Blood and urine samples will be collected at regular intervals for PK and safety analysis, 
as applicable, from admission until 48 hours post-dose during each period. Subjects will 
remain resident in the clinical unit during the washout period (minimum 4 days) between 
Periods 1 and 2. Subjects will be discharged from the clinical unit at 48 hours post-dose 
(Day 3) in Period 2. 
Following dosing of Regimens A and B, there will be an interim decision meeting to 
review available PK and safety data to decide the dose level and prandial state for 
Regimen C. The Investigator and Sponsor will decide whether to continue to evaluate a 
450 mg dose level of delafloxacin Powder for Oral Suspension following a high-fat 
breakfast, or to evaluate an alternative dose level in the fasted state. 
Period 3 
Subjects will be admitted in the evening on the day before dosing (Day -1). Subjects will 
fast overnight from all food and drink (except water) for a minimum of 10 hours, and will 
be administered IMP on the morning of Day 1 in the fasted state (if a different dose level 
is selected), or approximately 30 minutes after a high-fat breakfast (if a change to 
prandial state is selected). Subjects will complete a written taste/palatability 
questionnaire individually and privately following IMP administration. 
Blood and urine samples will be collected at regular intervals for PK and safety analysis, 
as applicable, from admission until 48 hours post-dose (Day 3), at which time subjects 
will be discharged from the clinical unit.  
Following dosing of Regimen C, there will be an interim decision meeting to review 
available PK and safety data, to decide whether to proceed with optional Period 4 or 
whether to end the study. If it is decided to end the study, a follow-up phone call will take 
place on Day 6 ± 1 to ensure the ongoing wellbeing of subjects. If a subject reports any 
AEs that present a cause for concern, they will be required to attend the clinical unit for 
an (unscheduled) follow-up visit. End of study is defined as completion of the last 
follow-up phone call or unscheduled follow-up visit. If it is decided to proceed with 
optional Period 4, the dose level and prandial state for Regimen D will be determined; 
the Investigator and Sponsor will decide whether to continue to evaluate the dose level 
selected for Regimen C following a high-fat breakfast, or to evaluate an alternative dose 
level in the fasted state.  
Optional Period 4 
Subjects will be admitted in the evening on the day before dosing (Day -1). Subjects will 
fast overnight from all food and drink (except water) for a minimum of 10 hours, and may 
be administered IMP on the morning of Day 1 in the fasted state (if a different dose level 
is selected), or approximately 30 minutes after a high-fat breakfast (if a change to 
prandial state is selected). Subjects will complete a written taste/palatability 
questionnaire individually and privately following IMP administration. 
Blood and urine samples will be collected at regular intervals for PK and safety analysis, 
as applicable, from admission until 48 hours post-dose (Day 3), at which time subjects 
will be discharged from the clinical unit. A follow-up phone call will take place on 
Day 6 ± 1 to ensure the ongoing wellbeing of subjects. If a subject reports any AEs that 
present a cause for concern, they will be required to attend the clinical unit for an 
(unscheduled) follow-up visit; completion of the last follow-up phone call or unscheduled 
follow-up visit will be considered the end of the study. 

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Figure 1 
Study Sequence  
Screening 
Day -28 to Day -2 
 
Periods 1 to 4b 
 
 
Admission 
Day -1a 
 
 
 
 
Dose 
Day 1 
 
 
 
Discharge 
Day 3c 
 
 
 
 
Follow-Up Phone Calld 
Day 6 ± 1 
 
a Subjects will be admitted to the clinical unit in the morning on the day before dosing (Day -1) in Period 1, 
and in the evening on the day before dosing (Day -1) in Period 3 and optional Period 4. Subjects will remain 
resident in the clinical unit between Periods 1 and 2; therefore, no admission procedures will be conducted 
for Period 2 
b Period 4 is optional 
c Periods 2 to 4 only. Subjects will remain resident in the clinical unit between Periods 1 and 2; there will be 
a minimum washout of 4 days between dosing in Periods 1 and 2 
d A follow-up phone call will take place on Day 6 ± 1 of the final treatment period, to ensure the ongoing 
wellbeing of the subjects. If a subject reports any AEs that present a cause for concern, they will be required 
to attend the clinical unit for an (unscheduled) follow-up visit 
8.2 
Criteria for In-Study Decisions  
In-study decisions will be made by the safety advisory committee (SAC), which will 
always comprise the Investigator, the Sponsor’s representative medical monitor or the 
Sponsor’s medically qualified designee who is familiar with the study protocol and IB, 
and a PK expert where appropriate. 
 Decision Points  
The following in-study decisions will be made during this study: 
• 
Dose level and prandial status selection for Regimen C. 
• 
Whether to proceed with optional Period 4. 
• 
Dose level and prandial status selection for Regimen D (if applicable). 
 Criteria for Dose Level and Prandial Status Selection  
Dose level and prandial status selection for Regimen C and Regimen D (if applicable) 
will only be made after a complete review of all data collected from the previous dose 
period(s). For dose level and prandial status selection to occur, data must be available 
from a minimum of 12 subjects who have completed the planned PK and safety 
assessments up to 48 hours after dosing. If data are not available for 12 subjects, the 
Investigator, Scientific Lead, and Sponsor will take a decision as to whether the data 
available are sufficient to support the dose level and prandial status selection decision. 
If data in fewer subjects are used in the decision process, additional subjects will not be 
dosed to increase the number of subjects in the completed regimen; however, additional 
subjects may be enrolled to achieve the target number of subjects for subsequent 
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Regimens C and D will only be administered in the fed state if the selected dose level 
has previously been administered in the fasted state. 
The following data are required: 
• 
AEs. 
• 
Vital signs. 
• 
ECGs. 
• 
Safety laboratory tests. 
• 
Plasma concentrations of delafloxacin. 
• 
PK parameter estimates (Cmax, Tmax, AUC(0-last), AUC(0-inf) and Frel 
comparisons) up to 48 hours post-dose. 
The dose(s) selected for Regimen C or Regimen D (if applicable) will only be selected 
from the design space of 300 mg to 600 mg. 
The decisions on dose level and prandial status will be made by the SAC. The decision 
will be documented and signed by the Investigator as per Quotient Sciences’ current 
standard operating procedure (SOP). Evidence of the decision will be retained in the ISF. 
8.3 
Subject Withdrawal  
If a subject wishes to leave the study at any time, they will be permitted to do so. Every 
reasonable effort will be made by Quotient Sciences to complete a final 
assessment/discharge procedures. Quotient Sciences will advise the Sponsor of the 
withdrawal of any subject from the study. 
Early withdrawal is defined as the date of the decision to withdraw the subject from the 
study. Subject completion is defined as the date of the last procedure conducted or last 
contact (e.g., follow-up phone call or unscheduled follow-up visit) for that subject. 
If a subject requests to leave the clinical unit earlier than the planned discharge time 
e.g., due to unforeseen personal circumstances, but aims to return to the clinical unit to 
complete the study, this will be documented as a subject self-discharge and a protocol 
deviation. The subject must complete the planned assessments/discharge procedures 
before discharge from the clinical unit, and may return for the next study 
period/assessments, as planned following agreement between the Sponsor and the 
Investigator.  
Subjects will be withdrawn from the study drug(s) for the following reasons: 
• 
Experiencing a serious or severe AE including but not limited to: 
− corrected QT interval by Fridericia’s formula (QTcF) of >500 msec or 
increase in QTcF interval of >60 msec from baseline (confirmed following 
a repeat ECG). 
− ALT concentration >3 × the upper limit of the reference range (confirmed 
following a repeat ALT blood test). 
• 
Pregnancy. 
• 
Termination of the study. 
• 
Upon the subject’s request (withdrawal of consent). 
• 
Significant deviation from the protocol. 
• 
Concurrent illness that would adversely affect subject safety or data integrity or 
requirement for prohibited medication. 

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• 
At the discretion of the Investigator. 
For the purpose of withdrawal criteria, baseline will be considered as the last available 
assessment prior to dosing in Period 1. 
For a subject who withdraws because of an IMP-related AE, every effort will be made to 
ensure the subject completes follow-up procedures. 
Early withdrawal of consent by the subject to participate in any further activities will be 
distinguished from withdrawal for any of the other above reasons. 
8.4 
Subject Replacement  
Withdrawn subjects may be replaced, at the discretion of the Investigator and Sponsor, 
with the aim of ensuring that the objectives of the trial can be met.  
Replacement subjects enrolled will be dosed with the next planned regimen of the 
withdrawn subject, and they will not receive any regimen that the withdrawn subject has 
already received, with the exception of the need to increase subject numbers to obtain 
the minimum number of evaluable subjects required for interim decisions, and to obtain 
data in any other regimen that is required for a valid comparison e.g., test vs reference, 
fed vs fasted. 
Any subject withdrawn due to an IMP-related AE will not be replaced. 
Subjects withdrawing for other reasons may be replaced. 
Up to 4 replacement subjects may be enrolled into the study. The maximum number of 
subjects that may be dosed is 20. 
8.5 
Stopping Criteria 
The study will be halted, and the risk to other subjects evaluated if any of the following 
criteria are met:  
• 
A SAR (i.e., a SAE considered at least possibly related to the IMP administration) in 
1 subject. 
• 
Severe non-serious adverse reactions (i.e., severe non-serious AE considered as at 
least possibly related to the IMP administration) in 2 subjects in the same cohort, 
independent of within or not within the same system organ class. 
Relatedness to IMP will be determined by the Investigator.  
If the study is halted, a temporary halt will be submitted to the Medicines and Healthcare 
products Regulatory Agency (MHRA) and ethics committee (EC) in the form of a 
substantial amendment. The study may be resumed or terminated; however, it will not 
be resumed until a further substantial amendment to resume the study is submitted and 
approved by MHRA and EC. 
8.6 
Study Termination  
After the start of protocol activities but prior to the commencement of dosing, the study 
may be terminated by the Sponsor and Investigator without consultation with the MHRA 
and EC. Notification of early termination must be provided to the MHRA and EC 

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immediately, and at the latest within 15 days after the study is terminated, clearly 
explaining the reasons. A description of follow-up measures taken for safety reasons, if 
applicable, will also be provided. 
If the study is abandoned prior to commencement of any protocol activities, the 
Investigator or Sponsor must notify the EC and MHRA by letter outlining the reasons for 
abandonment of the trial. 
8.7 
Lost to Follow-up  
A subject will be considered lost to follow-up if they fail to return for scheduled visits and 
cannot be contacted by the clinical unit.  
If a subject fails to return to the clinical unit for a required study visit: 
• 
The clinical unit must attempt to contact the subject and reschedule the missed visit 
as soon as possible. 
• 
Before a subject is deemed lost to follow-up, the Investigator or designee must make 
every effort to regain contact with the participant (e.g., three telephone calls on three 
separate occasions and, if necessary, an email or letter to the participant’s last known 
email/postal address). These contact attempts should be documented in the 
subject’s source. 
• 
If the subject cannot be contacted, they will be considered lost to follow-up. 
8.8 
Treatment Assignment and Randomisation  
Periods 1 and 2 are randomised; therefore, a randomisation schedule will be produced 
for these periods. 
Instructions to dispense and dose will be produced prior to dosing using the 
randomisation schedule and will be retained in the ISF. 
The original randomisation schedule and proof of quality control (QC) procedures will be 
held by the Data Sciences department at Quotient Sciences until the study is archived, at 
which time the randomisation materials will be retained in the ISF. 
Using a computer-generated randomisation schedule, subject numbers will be allocated to 
one of two sequences in a 1:1 ratio (AB or BA [see Table 2 for regimen details]). The 
allocation will be balanced, with 8 subjects receiving each sequence. 
Subjects will be randomised immediately prior to dosing in Period 1. 
Period 3 and optional Period 4 are non-randomised; therefore, a randomisation schedule 
will not be produced for these periods. Instructions to dispense and dose will be produced 
prior to dosing with IMP, which will dictate the order in which the treatments should be 
administered to each subject. The instructions to dispense and dose will be retained in 
the ISF. 
 Subject Numbers  
Subject numbers will be allocated on the morning of dosing according to the code 
 to 
 using the lowest number available. Replacement subjects will be allocated subject 
numbers 
 to 
 where the last two digits are the same as those of the original 
subject (e.g., if Subject 
 withdraws, the replacement will have the Subject 

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Number 
 and will receive any regimens which Subject 
 did not receive, in addition 
to any regimens which are required to make the required comparison of interest).  
 Blinding  
This is an open-label study and therefore blinding is not required.  
9 Selection of Subjects  
Subjects will be recruited from the Quotient Sciences panel or by direct advertising to the 
public.  
Before subjects are admitted to the clinical unit, The Over Volunteering Prevention 
System (TOPS) will be checked to ensure that each subject has not been dosed in a 
study within 90 days of the planned first dose date of this study, or less than 5 elimination 
half-lives prior to the planned first dose date of this study, whichever is longer.  
9.1 
Informed Consent  
Subjects will be provided with a written explanation of the study at least the day before 
the screening visit. Additionally, subjects may be provided with an information video 
before the screening visit that introduces them to the study. In the video and/or during 
the screening visit, a physician or nurse will explain to each subject the nature of the 
study, its purpose, expected duration and the benefits and risks involved in study 
participation. Subjects will be informed that, for safety reasons, brief details of their 
involvement in the study may be revealed to other units and companies that carry out 
clinical studies nationally. Subjects will then be given the opportunity to ask questions 
and will be informed of their right to withdraw from the study without prejudice. After this 
explanation and before entering the study, the subject will voluntarily sign an informed 
consent form (ICF). Until written consent has been obtained from the subject no study 
specific procedure or investigation will be performed. If an amendment is made to the 
participant information sheet (PIS), participants will be re-consented to the most current 
version of the ICF(s) where appropriate. 
9.2 
Inclusion Criteria  
Informed Consent and Compliance 
 Must provide written informed consent. 
 Must be willing and able to communicate and participate in the whole study. 
Demographics and Contraception  
 Aged 18 to 55 years inclusive at the time of signing informed consent. 
 Must agree to adhere to the contraception requirements defined in Section 9.4. 
Baseline Characteristics 
 Healthy males or non-pregnant, non-lactating healthy females. 
 Body mass index (BMI) of 18.0 to 32.0 kg/m2 as measured at screening. 
 Weight ≥50 kg at screening. 
Inclusion criteria 2, 4 and 5 from the list above will be re-assessed at admission/pre-dose 
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9.3 
Exclusion Criteria  
Medical/Surgical History and Mental Health 
 SAR (severe adverse reaction) or serious hypersensitivity to any drug or formulation 
excipients. 
 Any history of hypersensitivity to delafloxacin or any other fluroquinolones or previous 
history of tendon disorders related to fluroquinolone administration. 
 Presence or history of clinically significant allergy requiring treatment, as judged by 
the Investigator. Hay fever is allowed unless it is active. 
 History of clinically significant cardiovascular, renal, hepatic, respiratory, particularly 
GI disease, especially peptic ulceration, GI bleeding, ulcerative colitis, Crohn’s 
Disease or Irritable Bowel Syndrome, and neurological or psychiatric disorders. 
 Subjects with a history of cholecystectomy or gallstones. 
 Acute diarrhoea or constipation in the 7 days before the predicted Day 1. If screening 
occurs >7 days before the Day 1, this criterion will be determined on Day 1. Diarrhoea 
will be defined as the passage of liquid faeces and/or a stool frequency of greater 
than 3 times per day. Constipation will be defined as a failure to open the bowels 
more frequently than every other day. 
 Subject has a medical condition that may adversely affect taste or smell activity 
including but not limited to mouth ulcers, significant gum disease, and respiratory 
and/or sinus infection or cold. 
 Subject does not agree to the consumption of, or has any known allergies to, the 
formulation excipients. 
Physical Examination 
 Subjects who do not have suitable veins for multiple venepunctures/cannulation as 
assessed by the Investigator or delegate at screening or admission. 
Diagnostic Assessments 
 Clinically significant abnormal clinical chemistry, haematology or urinalysis as judged 
by the Investigator (laboratory parameters are listed in Appendix 1). Subjects with 
Gilbert’s Syndrome are not allowed. 
 Positive hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (HCV Ab), or 
human immunodeficiency virus (HIV) 1 and 2 antibody results. 
 Females who are pregnant or lactating (all female subjects must have a negative 
highly sensitive urine or serum pregnancy test). 
Prior Study Participation 
 Subjects who have received any IMP in a clinical research study within the 90 days 
of the planned first dose date, or less than 5 elimination half-lives prior to the planned 
first dose date, whichever is longer. 
 Donation of blood or plasma within the previous 3 months or loss of greater than 
400 mL of blood. 
Prior and Concomitant Medication 
 Subjects who are taking, or have taken, any prescribed or over-the-counter drug or 
herbal remedies (other than up to 4 g of paracetamol per day, hormonal 
contraception, or HRT) in the 14 days before the first dose of IMP (see Section 11.4). 
Exceptions may apply, as determined by the Investigator, if each of the following 
criteria are met: medication with a short half-life if the washout is such that no 
pharmacodynamic activity is expected by the time of dosing with IMP; and if the use 

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of medication does not jeopardise the safety of the trial subject; and if the use of 
medication is not considered to interfere with the objectives of the study. 
 Subjects who are taking, or have taken, any antibacterial medications, antacids, 
medications containing multivalent cations or metal cations, multivitamin 
preparations containing zinc or iron, or didanosine buffered tablets within 14 days 
prior to the first dose of IMP. 
 Subjects who have had a COVID-19 vaccine within 2 days (48 hours) prior to 
admission. 
Lifestyle Characteristics 
 History of any drug or alcohol abuse in the past 2 years. 
 Regular alcohol consumption in males >21 units per week and in females >14 units 
per week (1 unit = ½ pint beer, or a 25 mL shot of 40% spirit, 1.5 to 2 units = 125 mL 
glass of wine, depending on type). 
 A confirmed positive alcohol breath test at screening or admission. 
 Current smokers and those who have smoked within the last 12 months. 
 Current users of e-cigarettes and nicotine replacement products and those who have 
used these products within the last 12 months. 
 A confirmed breath carbon monoxide reading of greater than 10 ppm at screening or 
admission. 
 Confirmed positive drugs of abuse test result (drugs of abuse tests are listed in 
Appendix 1) at screening or admission. 
Other 
 Male subjects with pregnant or lactating partners. 
 Subjects who are, or are immediate family members of, a study site or Sponsor 
employee. 
 Subjects who do not agree to eat a high-fat breakfast. 
 Failure to satisfy the Investigator of fitness to participate for any other reason. 
Exclusion criteria 3, 6, 7, 9, 10, 12, 14, 15, 16, 17, 20, 23, 24, 25 and 28 from the list 
above will be re-assessed at admission/pre-dose in Period 1. 
Healthy subjects who do not meet the inclusion/exclusion criteria for the study will not be 
enrolled. 
9.4 
Contraception and Restrictions  
Male Subjects with Partners of Childbearing Potential 
Male subjects who are sexually active with a partner of childbearing potential must use, 
with their partner, a condom plus an approved method of highly effective contraception 
from the time of informed consent until 93 days after last IMP administration. This has 
been calculated based on 90 days (one cycle of spermatogenesis) plus 5 half-lives of 
the IMP. Five half-lives has been calculated as 3 days.  
The following methods are acceptable: 
• 
Partner’s use of combined (oestrogen and progestogen-containing) hormonal 
contraception associated with inhibition of ovulation:  
− oral 
− intravaginal 
− transdermal 

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• 
Partner’s use of progestogen-only hormonal contraception associated with inhibition 
of ovulation:  
− oral 
− injectable/implantable 
− intrauterine hormone-releasing system 
• 
Partner’s use of intrauterine device. 
• 
Vasectomised. 
• 
Partner’s bilateral tubal occlusion. 
These contraception requirements are considered to be more conservative than the 
guidance issued by the Heads of Medicines Agency: Clinical Trials Facilitation Group [9]. 
Males with Partners of Non-childbearing Potential 
There is a significant risk of drug exposure through the ejaculate (which also applies to 
vasectomised males) that might be harmful to sexual partners. Therefore, even if a male 
is sexually active with a partner of non-childbearing potential they will be required to use 
a condom from first administration of IMP until the follow-up phone call.  
Female Subjects of Childbearing Potential 
Female subjects who are sexually active and of childbearing potential must use, with 
their partner, an approved method of highly effective contraception from the time of 
informed consent until 33 days after last IMP administration. This has been calculated 
based on 30 days (one female menstrual cycle) plus 5 half-lives of the IMP. Five half-lives 
has been calculated as 3 days.  
The following highly effective methods are acceptable: 
• 
Combined (oestrogen and progestogen-containing) hormonal contraception 
associated with inhibition of ovulation:  
− oral  
− intravaginal  
− transdermal  
• 
Progestogen-only hormonal contraception associated with inhibition of ovulation. 
− oral  
− injectable/implantable 
− intrauterine hormone-releasing system  
• 
Intrauterine device. 
• 
Vasectomised partner. 
• 
Bilateral tubal occlusion. 
Female subjects are not required to use any of the above contraceptive methods if their 
sexual partner is female. 
These contraception requirements are considered to be more conservative than the 
guidance issued by the Heads of Medicines Agency: Clinical Trials Facilitation Group [9]. 

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All Male Subjects and Female Subjects of Childbearing Potential 
Alternatively, sexual abstinence is considered a highly effective method only if defined 
as refraining from heterosexual intercourse during the entire period of risk associated 
with the study treatments. The reliability of sexual abstinence needs to be evaluated in 
relation to the duration of the clinical trial and the preferred and usual lifestyle of the 
subject. 
Females of Non-Childbearing Potential  
Female subjects who are not of childbearing potential do not need to use any methods 
of contraception. A woman is considered of childbearing potential unless 
post-menopausal or permanently sterile. Permanent sterilisation methods include 
hysterectomy, bilateral salpingectomy and bilateral oophorectomy. A post-menopausal 
state is defined as no menses for 12 months without an alternative medical cause and 
confirmed by a follicle stimulating hormone (FSH) result of ≥40 IU/L. 
 Sperm Donation  
Male subjects should not donate sperm for the duration of the study and for 93 days after 
last IMP administration. 
 Egg Donation  
Female subjects should not participate in egg donation from dosing, for the duration of 
the study and for at least 33 days after last IMP administration. 
9.5 
Pregnancy  
Subjects will be instructed that if they/their partner becomes pregnant during the study 
this should be reported to the Investigator. The Investigator should also be notified of 
pregnancy occurring during the study but confirmed after completion of the study. In the 
event that a subject/subject’s partner is subsequently found to be pregnant after the 
subject is included in the study, then consent will be sought from the subject/subject’s 
partner and, if granted, any pregnancy will be followed and the status of mother and/or 
child(ren) will be reported to the Sponsor after delivery. Any subject reporting a 
pregnancy during the study will be discontinued from the study treatment and every 
reasonable effort will be made by Quotient Sciences to follow up the pregnancy until 
delivery. 
A pregnancy notification form and follow-up will be completed. 
9.6 
Additional Study Restrictions  
The following additional restrictions will be in place for the duration of the study: 
 Subjects must not eat anything likely to disturb GI transit (e.g., spicy or high-fat meals 
such as curry or fish and chips, or foods of a high-fibre content, such as All-Bran) for 
24 hours prior to each admission until discharge from the clinical unit. 
 Subjects must abstain from alcohol during the 24 hours prior to screening and the 
24 hours prior to each admission until discharge from the clinical unit. 
 Subjects must not drink liquids or eat food containing grapefruit, cranberry, caffeine 
or other xanthines from 24 hours prior to each admission until discharge from the 
clinical unit. 

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 Subjects should refrain from eating food containing poppy seeds for 48 hours prior 
to screening and for 48 hours prior to each admission until discharge from the clinical 
unit. 
 Subjects must not take part in any unaccustomed or strenuous exercise from the 
72 hours before the screening visit and then from 72 hours prior to each admission 
until discharge from the clinical unit. 
 Must not donate blood or plasma (outside of this study), from clinical unit admission, 
from screening, throughout the study duration, and for at least 90 days following last 
dose of study medication. 
The additional restrictions above are not exclusion criteria; if non-compliance occurs, a 
protocol deviation will be completed.  
10 Study Procedures  
Study procedures will be performed as detailed in the study schedule of assessments in 
Appendix 2, and in accordance with Quotient Sciences’ SOPs unless otherwise stated 
in this protocol. 
10.1 Screening  
Within the 28 days preceding first dose, all subjects will be required to undergo a 
screening visit. Screening procedures will be carried out in accordance with the schedule 
of assessments. 
If the start of the study is delayed for any reason so that the interval between screening 
and first dose exceeds 28 days, all or part of the screening procedures will be repeated 
at the discretion of the Investigator. 
Screening safety procedures such as clinical laboratory tests, ECGs, vital signs, alcohol 
breath tests, carbon monoxide breath tests and urinalysis can be repeated as clinically 
indicated under the discretion of the Investigator or Sub-investigator if there is a concern 
regarding a subject’s safety or eligibility to participate in the trial. 
 Subject Re-Screening  
This study permits the re-screening of a subject who has discontinued the study as a 
pre-treatment failure (i.e., subject has not been dosed with IMP); the reason for failure 
must be temporary and expected to resolve. If re-screened, the subject must be 
re-consented. 
10.2 Admission and Pre-dose Procedures  
The identity of the subjects will be confirmed at each admission and pre-dose.  
In addition, the ongoing eligibility of subjects will be re-assessed at admission/pre-dose, 
as described in Sections 9.2 and 9.3.  
Admission/pre-dose safety procedures such as clinical laboratory tests, ECGs, vital 
signs, urinalysis and drugs of abuse tests can be repeated as clinically indicated under 
the discretion of Investigator or Sub-investigator if there is a concern regarding a 
subject’s safety or eligibility to participate in the clinical trial. 
Reserve subjects for the first dose occasion, in any group, will not require admission 
procedures to be repeated, if dosing is within 2 days.  

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If dosing is delayed, subjects who have completed admission procedures do not need 
admission procedures to be repeated if dosing is within 2 days and the subjects have 
remained resident in the clinical unit. 
The subjects will be admitted to the clinical unit in the morning on the day before dosing 
(Day -1) in Period 1, and in the evening on the day before dosing (Day -1) in Period 3 
and optional Period 4. Subjects will remain resident in the clinical unit between Periods 1 
and 2; therefore, no admission procedures will be conducted for Period 2. 
In addition, subjects may be required to visit the clinical unit on Day -1 of Periods 1, 3, 
and optional Period 4, prior to admission to the clinical unit, for SARS-CoV-2 antigen 
tests (if required; see Sections 6.4.2.2 and 14.5.8).  
The admission and pre-dose procedures are presented in the schedule of assessments. 
10.3 Study Day Procedures  
 Blood Volume  
The number and timing of samples may be amended following any interim PK parameter 
estimations. However, in this case, the total blood volume for each subject will not exceed 
550 mL in a 4-week period.  
The first 0.5 mL of blood withdrawn via cannula will be discarded. 
 Timing of Procedures  
There are times where the protocol requires more than one procedure to be completed 
at the same time point. 
As guidance, the preferred order of assessments is: 
 
 
 
 
Nominal time 
 
 
ECGs 
 
Vitals 
 
PK blood 
sampling 
 
Other assessments e.g., 
physical examinations 
When scheduled at the same 
time point, ECGs should be 
taken prior to vital signs, and 
both ECGs and vital signs will 
be performed prior to the PK 
samples 
Every effort will be made to 
take the PK sample at the 
protocol-specified time 
Other assessments will be 
performed within the required time 
windows 
All safety assessments will be timed and performed relative to the start of dosing.  
 Discharge from the Clinical Unit  
A subject will be allowed to leave the premises without additional Investigator or 
Sub-investigator review, following completion of study-specific procedures providing 
that: 
• 
No AEs have been reported during the study visit  
• 
The subject responds in the affirmative when asked if they are feeling well 
Refer to Section 8.1 for further details, and the schedule of assessments for 
study-specific procedures at subject discharge. As subjects will remain resident in the 
clinical unit between Periods 1 and 2, discharge procedures will apply to Periods 2 to 4 
only. 

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If any of these conditions are not met, then the subject will only be allowed to leave the 
clinical unit with the authorisation of the Investigator or Sub-investigator. 
There will be no continued provision of the study intervention or treatment for subjects, 
as this study involves healthy volunteers only. 
 Medical Supervision  
A physician will be responsible for the clinical aspects of the study and will be available 
at all times during the study. In accordance with the current Association of the British 
Pharmaceutical Industry guidelines [10], each subject will receive a card stating the 
telephone number of the Investigator and the 24/7 contact details of the Quotient 
Sciences’ on-call physician. 
 Follow-up  
A follow-up phone call will take place on Day 6 ± 1 of the final treatment period, to ensure 
the ongoing wellbeing of the subjects. If a subject reports any AEs that present a cause 
for concern, they will be required to attend the clinical unit for an (unscheduled) follow-up 
visit; assessments may be performed at the unscheduled follow-up visit, as detailed in 
the schedule of assessments. Completion of the last follow-up phone call or unscheduled 
follow-up visit will be considered the end of the study. 
11 Dosing of Subjects  
Dosing will be performed at the time points detailed in the study schedule of assessments 
in Appendix 2. 
11.1 Food and Fluid Intake  
Subjects will be allowed water up to 1 hour before the scheduled dosing time and will be 
provided with 240 mL of water at 1 hour post-dose (to ensure adequate hydration) and 
thereafter, water will be allowed ad libitum after 1 hour post-dose. Decaffeinated fluids 
will be allowed ad libitum from lunch time on the day of dosing. 
If, for technical reasons, dosing is delayed for more than 2 hours beyond the expected 
dosing time, subjects will receive 200 mL of an electrolyte drink (e.g., Lucozade Sport) 
at the originally scheduled dosing time, or earlier if possible. 
Fasted Dosing 
Fasted dosing will apply to regimens in Periods 1 and 2, and may apply to regimens in 
Period 3 or optional Period 4, unless fed dosing is selected during the relevant interim 
decision meeting, based on available PK and safety data.  
The calorie/fat content of meals are not required to be controlled. Subjects will be 
provided with a standardised menu.  
Subjects will be provided with a snack and then fast from all food and drink (except water) 
for a minimum of 10 hours on the day prior to dosing until approximately 4 hours 
post-dose, at which time lunch will be provided. An evening meal will be provided at 
approximately 10 hours post-dose and an evening snack at approximately 14 hours 
post-dose. On subsequent days, meals will be provided at appropriate times. 

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Fed Dosing  
Fed dosing may be selected for regimens in Period 3 or optional Period 4. 
The calorie/fat content of breakfast will be controlled on Day 1 (refer to Appendix 4 for 
breakfast content). Subjects will be provided with a standardised menu for all other 
meals.  
For fed regimens, a high-fat breakfast will be given approximately 30 minutes before 
dosing. 
Subjects will be provided with a snack and will fast for a minimum of 10 hours from all 
food and drink (except water) until the following morning, when they will be provided with 
a high-fat breakfast.  
The breakfast should be consumed over a maximum period of 25 minutes, with dosing 
occurring 30 ± 5 minutes after the start of breakfast. Subjects should be encouraged to 
eat their meal evenly over the 25 minute period. It is acknowledged that some subjects 
will take less time to eat, but dosing should still occur 30 ± 5 minutes after the start of 
breakfast. Subjects must consume at least 90% of the pre-dose breakfast in order to be 
eligible for dosing. The start and stop time and percentage of the breakfast consumed 
must be recorded in the source.  
Lunch will be provided at approximately 4 hours post-dose, an evening meal at 
approximately 10 hours post-dose and an evening snack at approximately 14 hours 
post-dose. On subsequent days, meals will be provided at appropriate times. 
11.2 Administration of Test Preparations  
Specific details of IMPs, and doses to be administered, are provided in Section 5.2 and 
Section 8.1, respectively. Subjects will be dosed on the morning of Day 1 of each study 
period.  
The exact time of dosing will be decided based on logistics and will be documented in 
the source. The order in which regimens are dosed may be subject to change due to 
logistical reasons. 
The minimum washout period between regimens may be changed, if data collected 
during the study support the change. However, the minimum washout period will not be 
reduced to less than 5 half-lives of the IMP. 
Subjects will receive single administrations of delafloxacin on up to 4 separate occasions. 
Oral tablets will be administered with a total of 240 mL of water. If required, additional 
water may be given with the IMP in 50 mL aliquots and will be recorded in the source but 
will not be classed as a protocol deviation. 
Immediately after administration of delafloxacin Powder for Oral Suspension, the dosing 
vessel will be rinsed with water and subjects will consume the rinse solution. Subjects 
will then consume further water to a total volume of 240 mL (including the dosing volume 
and volume used to rinse the dosing vessel). If required, additional water may be given 
with the IMP in 50 mL aliquots and will be recorded in the source but will not be classed 
as a protocol deviation. 

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11.3 Dosing Compliance  
During all clinical phases of the study, subjects will be observed by study staff to assure 
compliance to all study procedures, including dose administration.  
Mouth and hand checks will be conducted after dosing, as applicable, to ensure that the 
IMP has been swallowed.  
The date and time that each subject is dosed will be recorded in the subject’s source 
data. Any violation of compliance will require evaluation by the Investigator and Sponsor 
to determine if the subject can continue in the study. 
11.4 Prior and Concomitant Medications  
No prescribed, over-the-counter medication or herbal remedies will be permitted from 
14 days before the first dose of IMP until the follow-up phone call, except up to 4 g of 
paracetamol per day, hormonal contraception, or HRT, and those deemed necessary by 
the Investigator to treat AEs (see also Section 9.3). Any medications used will be 
recorded in the source. 
Subjects are not permitted to receive antibacterial medications, antacids, medications 
containing multivalent cations or metal cations, multivitamin preparations containing zinc 
or iron, or didanosine buffered tablets in the 14 days before the first dose of IMP until the 
follow-up phone call.  
Subjects are not permitted to receive a COVID-19 vaccine within 2 days (48 hours) prior 
to each admission, so that by the time of dosing, any effects of the vaccine (e.g., pyrexia, 
fatigue, pain/stiffness at site of injection) are likely to have abated. Additionally, 
COVID-19 vaccines will not be accepted concomitant medications for the duration of the 
study.  
Emergency equipment and drugs will be available within the clinical unit as per current 
standard procedures. In the unlikely event that they are required, their use will be 
documented. 
Medication taken within 14 days of informed consent will be recorded in the source.  
12 Assessment of Efficacy  
Not applicable for this Phase 1 study.  
13 Assessment of Pharmacokinetics, Taste/Palatability and 
Pharmacodynamics  
PK assessments will be performed as detailed in the study schedule of assessments in 
Appendix 2. 
13.1 Assessment of Pharmacokinetics  
 Pharmacokinetic Blood Sampling  
Venous blood samples will be collected from the subjects by a trained member of the 
clinical team. Consent will be collected from the subjects for use of these samples for the 
purposes of the proposed study. Samples will be processed to isolate plasma and PK 
analysis will be carried out on plasma samples. 

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Plasma samples will be sent for laboratory testing in linked anonymised form (subject 
number only). This information is able to be linked directly to the volunteer by the 
Quotient Sciences research team and study monitor, however not by the laboratory staff 
or Sponsor. 
Venous blood samples will be withdrawn via an indwelling cannula or by venepuncture 
at the time points detailed in the schedule of assessments. 
All PK windows will be timed relative to the start of dosing for each period. 
The acceptable deviations from the nominal blood sampling times are as follows: 
• 
Day 1: The pre-dose sample will be taken ≤1 hour before dosing. 
• 
0 to 1 hour post-dose samples will be taken within ± 2 minutes of the nominal 
post-dose sampling time. 
• 
1.5 hours to 12 hours post-dose samples will be taken within ± 10 minutes of the 
nominal post-dose sampling time. 
• 
14 hours to 48 hours post-dose samples will be taken within ± 30 minutes of the 
nominal post-dose sampling time. 
The timing and number of the samples may be amended following any interim PK 
parameter estimations, including collection over a longer duration. Any changes to blood 
sampling time points would be documented in the interim dose decision report and 
retained in the ISF. 
Samples will be collected into appropriate tubes as specified by the bioanalytical 
laboratory. Details of sample tubes and processing will be contained in the Clinical 
Sample Processing Manual (CSPM). 
Samples will be shipped to PPD, Inc. for the analysis of delafloxacin. 
13.2 Assessment of Pharmacodynamics  
Not applicable for this Phase 1 study. 
13.3 Taste/Palatability Evaluation  
Taste/palatability will be assessed using a questionnaire (example provided in 
Appendix 3) at the time points detailed in the schedule of assessments. The 
questionnaire will ask subjects to rate the overall acceptability of taste/palatability of each 
of the delafloxacin Powder for Oral Suspension (i.e., test) regimens, with additional 
questions asked on specific taste/palatability attributes (smell, sweetness, bitterness, 
flavour, mouth feel/texture, grittiness, and aftertaste), on a 9-point scale [11]. The clinical 
staff will provide definitions and examples of each aspect that is being rated if required. 
Subjects will be asked to rate each test regimen independently of any previous 
taste/palatability questionnaires. 
Each subject will complete the questionnaire individually and privately following each test 
IMP administration.  
The questionnaire will be started within 10 minutes of test IMP administration. 

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14 Assessment of Safety  
Safety assessments will be performed as detailed in the study schedule of assessments 
in Appendix 2. 
14.1 Definition and Classification of Adverse Events  
An AE is any untoward medical occurrence in a subject that occurs either before dosing 
(referred to as a pre-dose AE) or once a medicinal product has been administered, 
including occurrences which are not necessarily caused by or related to that product.  
An ADR is any AE where a causal relationship with the IMP is at least a reasonable 
possibility (possibly related or related). 
AEs will be monitored from the time that the subject signs the ICF until after the follow-up 
phone call/unscheduled follow-up visit. The severity of AEs should be assessed as 
follows: 
Mild 
An AE that is easily tolerated by the subject, causes minimal discomfort and 
does not interfere with everyday activities. 
Moderate An AE that is sufficiently discomforting to interfere with normal everyday 
activities; intervention may be needed. 
Severe 
An AE that prevents normal everyday activities; treatment or other 
intervention usually needed. 
14.2 Assessment of Causality  
Every effort should be made by the Investigator to try to explain each AE and assess its 
relationship, if any, to the IMP. The temporal relationship of the event to IMP 
administration should be considered in the causality assessment (i.e., if the event starts 
soon after IMP administration and resolves when the IMP is stopped). 
Causality should be assessed using the following categories:  
Unrelated: 
Clinical event with an incompatible time relationship to IMP 
administration, and that could be explained by underlying 
disease or other drugs or chemicals or is incontrovertibly not 
related to the IMP. 
Possibly related: 
Clinical event with a reasonable time relationship to IMP 
administration, and that is unlikely to be attributed to concurrent 
disease or other drugs or chemicals. 
Related: 
Clinical event with plausible time relationship to IMP 
administration and that cannot be explained by concurrent 
disease or other drugs or chemicals. 
The degree of certainty with which an AE is attributed to IMP administration (or 
alternative causes, e.g., natural history of the underlying disease, concomitant therapy) 
will be determined by how well the experience can be understood in terms of one or more 
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• 
Known pharmacology of the IMP. 
• 
Reactions of a similar nature have been previously observed with the IMP or this 
class of drug. 
• 
The experience being related by time to IMP administration, terminating with IMP 
withdrawal or recurring on re-challenge. 
• 
Alternative cause. 
14.3 Recording Adverse Events 
AEs (including SAEs) will be recorded from the time of providing written informed consent 
until discharge from the study at the follow-up phone call/unscheduled follow-up visit. 
During each study visit, the subject will be questioned directly regarding the occurrence 
of any adverse medical event according to the schedule in the source. All AEs, whether 
ascribed to study procedures or not, will be documented immediately in the subject’s 
source. This will include the date and time of onset, a description of the AE, severity, 
seriousness, duration, actions taken, outcome and an Investigator’s current opinion on 
the relationship between the study drug and the event. A diagnosis and final opinion on 
the relationship between the study drug and the event will be provided at the end of the 
study by the Investigator.  
Any subject who withdraws from the study due to an AE will be followed up until the 
outcome is determined and written reports are provided by the Investigator. 
14.4 Serious Adverse Events  
 Definition of Serious Adverse Events  
A SAE is defined as any untoward medical occurrence that at any dose:  
• 
Results in death. 
• 
Is life-threatening. 
• 
Requires hospitalisation or prolongation of existing hospitalisation. 
• 
Results in persistent or significant disability or incapacity. 
• 
Consists of a congenital anomaly or birth defect. 
• 
An important medical event as recognised by the Investigator. 
 Definition of Suspected Unexpected Serious Adverse Reactions  
Suspected unexpected serious adverse reactions (SUSARs) are AEs that are believed 
to be related to an IMP and are both unexpected (i.e., the nature or severity is not 
expected from the information provided in the IB) and serious. SUSARs are subject to 
expedited reporting to the MHRA (see Section 16.3.2 for details on reporting SUSARs). 
14.5 Laboratory Measurements  
Venous blood and urine samples will be collected from the subjects by a trained member 
of the clinical team. Consent will be collected from the subjects for use of these samples 
for the purposes of the proposed study. 
Blood and urine samples are sent for laboratory testing in linked anonymised form 
(subject number, gender and date of birth for analytical reasons). This information is able 
to be linked directly to the volunteer by the Quotient Sciences research team and study 
monitor; however, not by the laboratory staff or Sponsor. 

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Safety laboratory tests and virology will be carried out on blood samples, and drugs of 
abuse tests and urinalysis will be carried out on urine samples. The research will not 
involve analysis or use of human DNA. 
Blood and urine samples results will be reviewed by a physician and acted upon before 
the subject is dosed or receives their next dose, or is released from the study, as is 
appropriate. A list of the laboratory parameters measured is presented in Appendix 1. 
 Haematology and Clinical Chemistry  
Laboratory tests will be performed by The Doctors Laboratory at the time points detailed 
in the schedule of assessments. Blood samples will be collected and processed as 
detailed in the CSPM. Scheduled blood samples will be taken following an 8 hour fast. 
The acceptable deviations from the nominal blood sampling time points for laboratory 
assessments are: 
• 
The pre-dose blood sample will be taken ≤2 hours before dosing. 
• 
Post-dose blood samples will be taken ± 1 hour from the nominal blood sampling 
time. 
 Virology  
HBsAg, HCV Ab, and HIV 1 and 2 tests will be performed from the clinical chemistry 
sample (see Section 14.5.1 for sample collection and processing information). 
 Urinalysis  
Urinalysis will be performed on-site using a dipstick at the time points detailed in the 
schedule of assessments. Urine samples will be collected and processed as detailed in 
the CSPM. If microscopy is required, a urine sample will be sent to The Doctors 
Laboratory.  
The acceptable deviations from the nominal blood sampling time points for urinalysis are: 
• 
The pre-dose urine sample will be the first void of the day or a sample collected 
≤3 hours before dosing. 
• 
Post-dose urine samples will be taken ± 2 hours from the nominal urine sampling 
time. 
 Pregnancy Test  
Serum and urine highly sensitive pregnancy tests will be performed at the time points 
detailed in the schedule of assessments. The samples will be collected and processed 
as detailed in the CSPM.  
 Follicle-Stimulating Hormone Test  
Serum FSH tests will be performed at the time points detailed in the schedule of 
assessments. The samples will be collected and processed as detailed in the CSPM. 

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 Drug Screen  
A urine drug screen will be performed on-site using a point of care testing method 
(e.g., Alere Drug Screen Test Cup) at the time points detailed in the schedule of 
assessments. The sample will be collected and processed as detailed in the CSPM. 
Subjects will be screened for the drugs of abuse listed in Appendix 1.  
 Alcohol Breath Test  
An alcohol breath test will be performed at the time points detailed in the schedule of 
assessments. A confirmed positive result will exclude the subject from dosing during that 
admission. 
 Carbon Monoxide Breath Test  
A carbon monoxide breath test will be performed at the time points detailed in the 
schedule of assessments. A confirmed result of greater than 10 ppm will exclude the 
subject from the study. 
 SARS-CoV-2 Tests (If Required)  
Testing for the SARS-CoV-2 virus may be performed based on current infection rates 
and availability of tests. If required, the samples will be collected and processed as 
detailed in the Screening Sample Processing Manual and CSPM, as applicable. 
Testing time points may be changed and additional time points may be added throughout 
the study as required. The decision on COVID-19 testing and the definition of the testing 
time points are subject to change based on the current risk mitigation in place and will 
be agreed by the study team and documented in the ISF via the Clinical Kick-Off Meeting 
minutes or in a file note if the study is ongoing. 
 
Abnormal Laboratory Findings  
In cases where laboratory findings are outside the normal range and the Investigator 
believes that the results may be of clinical significance, repeat sampling may be 
requested as clinically indicated. If the abnormal finding is clinically significant, 
appropriate actions will be taken, e.g., the subject will not be entered into the study, or 
the subject may be withdrawn from the study. The subject will be referred to their general 
practitioner or other appropriate provider for further care if necessary. The same will 
apply if the results of the HBsAg, HCV Ab, or HIV test are positive and, in addition, the 
Investigator will ensure that adequate counselling is available if requested. 
Abnormal results at follow-up assessments will also require repeat testing if the 
Investigator believes the results may be of clinical significance. 
Any clinically significant abnormality, including changes from baseline, must be reported 
as an AE. 
Additional blood and/or urine samples may be taken for safety tests. Furthermore, 
additional assays outside those specified in the protocol may be performed for safety 
reasons as requested by the Investigator or Sub-investigator. 

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14.6 Vital Signs Measurements  
Blood pressure and heart rate will be measured by an automated recorder after the 
subject has been in a supine position for a minimum of 5 minutes, and oral temperature 
and respiratory rate will be measured at the time points detailed in the schedule of 
assessments. The acceptable deviations from the nominal vital signs measurement time 
points are: 
• 
The pre-dose vital signs measurements will be taken ≤2 hours before dosing. 
• 
Post-dose vital signs measurements will be taken ± 15 minutes from the nominal 
post-dose time points. 
• 
Discharge vital signs measurements will be taken ± 1 hour from the nominal time 
point. 
If a subject shows an abnormal assessment at any stage, repeat measurements may be 
made and the abnormality followed to resolution if required. Additional measurements 
may be taken as deemed necessary by the Investigator or Sub-investigator. 
Any clinically significant abnormality, including changes from baseline, must be reported 
as an AE. 
14.7 ECG Measurements  
Single 12-lead ECGs will be measured after the subject has been in the supine position 
for a minimum of 5 min at the time points detailed in the schedule of assessments. The 
acceptable deviations from the nominal ECG measurement time points are: 
• 
The pre-dose ECG measurements will be taken ≤2 hours before dosing. 
• 
Post-dose ECG measurements will be taken ± 15 minutes from the nominal 
post-dose time point. 
• 
Discharge ECG measurements will be taken ± 1 hour from the nominal time point. 
If a subject shows an abnormal assessment at any stage, repeat measurements may be 
made and the abnormality followed to resolution if required. Additional measurements 
may be taken as deemed necessary by the Investigator or Sub-investigator. 
Any clinically significant abnormality, including changes from baseline, will be reported 
as an AE. 
14.8 Body Weight, Height and BMI  
The subject’s body weight and height will be measured, and their BMI will be calculated 
at the time points detailed in the schedule of assessments. 
14.9 Physical Examination  
Subjects will undergo a physical examination at the time points detailed in the schedule 
of assessments. 
In the targeted (symptom driven) physical examination, a physician will assess the 
subject; if the subject reports feeling unwell or has ongoing AEs, then the physician will 
examine the appropriate body system(s) if required. 

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14.10 Additional Safety Procedures  
Additional non-invasive procedures that are already specified in the protocol may be 
performed, if it is believed that an important effect of the IMP(s) is occurring or may occur 
at a time when no measurements are scheduled, or if extra procedures are needed in 
the interests of safety. 
Additional blood samples for safety assessments may be taken if required by the 
Investigator or Sub-investigator at any point. 
15 Statistics and Data Analysis  
15.1 Sample Size Justification  
The study is exploratory, and no formal sample size calculation has been made. Based 
on experience from previous studies of a similar design, a sample size of 16 subjects 
and a minimum of 12 evaluable subjects is considered sufficient to meet the objectives 
of the study. 
15.2 Data Management  
Data management will be performed by Quotient Sciences. 
Study data will be managed using a validated electronic case report form (eCRF) 
database system and subjected to data consistency and validation checks. Data queries 
will be raised within the study eCRF database by data management staff and resolved 
with the assistance of clinical staff. 
AEs, medical histories and medications will be coded using the Medical Dictionary for 
Regulatory Activities (MedDRA) (version to be specified in the Data Management Plan 
[DMP]) and the World Health Organization (WHO) Drug Dictionary Global Drug 
Reference (version to be specified in the DMP), respectively. An independent coding 
review will also be performed within the Data Sciences department. 
Clinical chemistry and haematology data (and other safety laboratory data) will be 
collected by a central laboratory (The Doctors Laboratory) and stored electronically in 
their clinical pathology system. The data will be transferred electronically to Quotient 
Sciences, and all demographic details and sample dates will be cross-referenced with 
the corresponding data on the study database. All queries will be resolved with the 
assistance of laboratory staff, or if necessary, clinical staff.  
The database will be closed after all queries have been resolved. The database will be 
locked when all criteria listed in the DMP are met.  
Further details are addressed in the DMP. 
15.3 Pharmacokinetic Data Analysis  
The plasma concentration data for delafloxacin provided by PPD, Inc. will be analysed 
by Quotient Sciences, using Phoenix WinNonlin v8.3 or a more recent version (Certara 
USA, Inc., USA). 
PK analysis of the concentration time data obtained will be performed using appropriate 
non-compartmental techniques to obtain estimates of the PK parameters presented in 
Table 3, where possible and appropriate. 

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Table 3 
Plasma Pharmacokinetic Parameters  
Parameter 
Definition 
Tlag 
Time prior to the first measurable concentration 
Tmax 
Time of maximum observed concentration 
Cmax 
Maximum observed concentration 
AUC(0-24) 
Area under the curve from time 0 to 24 h post-dose 
AUC(0-last) 
Area under the curve from time 0 to the time of last measurable concentration 
AUC(0-inf) 
Area under the curve from time 0 extrapolated to infinity 
AUCextrap 
Area under the curve from time of the last measurable concentration to infinity as a 
percentage of the area under the curve extrapolated to infinity 
T1/2  
Terminal elimination half-life 
Lambda-z 
First order rate constant associated with the terminal (log-linear) portion of the curve 
CL/F 
Total body clearance calculated after a single extravascular administration where F 
(fraction of dose bioavailable) is unknown 
Vz/F 
Apparent volume of distribution based on the terminal phase calculated using 
AUC(0-inf) after a single extravascular administration where F (fraction of dose 
bioavailable) is unknown 
MRT(0-last) 
Mean residence time from time 0 to time of the last measurable concentration 
MRT(0-inf) 
Mean residence time from time 0 extrapolated to infinity 
Frel Cmax 
Relative bioavailability based on Cmax 
Frel AUC(0-last) 
Relative bioavailability based on AUC(0-last) 
Frel AUC(0-inf) 
Relative bioavailability based on AUC(0-inf) 
Interim PK parameter estimations will be provided for dose level and prandial state 
selection purposes, as described in Section 8.2. 
Further details of the PK data analysis will be included in the reporting and analysis plan 
(RAP). 
15.4 Statistical Data Analysis  
Statistical analysis and production of summary tables, figures, and listings for this study 
will be performed by Quotient Sciences using the statistical package SAS (v9.4 or more 
recent version).  
In general terms, categorical data (including TEAEs) will be presented using counts and 
percentages, while continuous variables will be presented using the mean, median, 
standard deviation, minimum, and maximum. Additional statistics will be provided for 
PK-related data including coefficient of variation (CV%), geometric mean, and geometric 
CV%.  
Descriptive summaries for all safety data (AEs, vital signs, ECGs, and safety laboratory 
assessments) by regimen will be provided (including changes from baseline as required). 
Descriptive summaries for all PK and taste data by regimen, as applicable, will be 
provided.  
All PK, safety, and taste data will be listed. 

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Formal statistical analysis will be performed on the PK parameters Cmax, AUC(0-last), 
and AUC(0-inf) to assess relative bioavailability. The PK parameters will undergo a 
natural logarithmic transformation and will be analysed using a mixed effect model, with 
terms for sequence and regimen as fixed effects, and subject within sequence as a 
random effect. Adjusted geometric mean ratios (GMRs) and 90% confidence intervals 
(CIs) for the adjusted GMRs for the relevant comparison (i.e., Regimen A [reference] and 
Regimen B [test]) will be provided, where the ratios are defined as test/reference.  
Formal statistical analysis will also be performed on the PK parameters Cmax, 
AUC(0-last), and AUC(0-inf) to assess for the effects of food on delafloxacin Powder for 
Oral Suspension regimens administered at the same dose level. The PK parameters will 
undergo a natural logarithmic transformation and will be analysed using a mixed effect 
model, with terms for regimen as fixed effect, and subject as a random effect. Adjusted 
GMRs and 90% CIs for the adjusted GMRs for the comparison between fed and fasted 
regimens will be provided, where the ratios are defined as fed/fasted.  
Additionally, formal statistical analysis may be performed on log-transformed, 
dose-corrected PK parameters Cmax, AUC(0-last), and AUC(0-inf) to assess dose 
proportionality, if two dose levels of delafloxacin Powder for Oral Suspension are 
administered in the same prandial state, using a mixed effect model, with terms for 
regimen as a fixed effect and subject as a random effect. 
No formal hypothesis will be tested, and the results will be interpreted from GMRs and 
corresponding 90% CIs. 
Populations and analysis sets will be determined for PK, safety, and taste data after 
database lock, when the relevant data are available, using the criteria defined in the 
RAP; the RAP will be signed off prior to database lock. 
Further details relating to the statistical analysis will be included in the RAP including the 
following: 
• 
Criteria to be used to define each of the population and analysis sets. 
• 
Additional detail covering the analyses and/or description of primary and secondary 
analyses and safety data. 
• 
Handling of missing data, unused or spurious data. 
• 
Handling of data from withdrawn subjects. 
15.5 Interim Analysis  
No formal interim analyses are planned for this study. Interim data reviews will be 
performed as detailed in Section 8.2. 
16 Safety Reporting to Regulatory Authorities and Ethics 
Committees  
16.1 Events Requiring Expedited Reporting  
SUSARs (as defined in Section 14.4.2) are subject to expedited reporting to the 
appropriate regulatory authority. 
In addition to SUSARs, other safety issues may qualify for expedited reporting where 
they might materially alter the current benefit-risk assessment of an IMP or that would 

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be sufficient to consider changes in the IMPs’ administration or in the overall conduct of 
the study, for instance: 
• 
An increase in the rate of occurrence or a qualitative change of an expected SAR, 
which is judged to be clinically important. 
• 
SAEs that occur after the subject has completed the clinical study, where the Sponsor 
considers them to be a SUSAR. 
• 
New events related to the conduct of the study or the development of the IMPs and 
likely to affect the safety of the subjects, such as: 
− An SAE which could be associated with the study procedures, and which 
could modify the conduct of the study. 
− A major safety finding from a newly completed animal study (such as 
carcinogenicity). 
− Any anticipated end or temporary halt of a study for safety reasons and 
conducted with the same IMPs in another country by the same Sponsor. 
16.2 Urgent Safety Measures  
If Quotient Sciences, or any of its staff or contractors, becomes aware of an actual or 
potential urgent safety issue, then the Sponsor must be immediately contacted so that 
appropriate urgent safety measures can be agreed. An urgent safety issue is defined as:  
• 
An immediate hazard to the health or safety of subjects participating in a clinical study 
• 
A serious risk to human health or potentially a serious risk to human health 
An urgent safety issue may include issues with an investigational drug or comparators, 
study procedures, inter-current illness (including pandemic infections), concomitant 
medications, concurrent medical conditions, or any other issues related to the safe 
conduct of the study or that pose a risk to study subjects. 
In exceptional circumstances of imminent hazard and in order to safeguard the health or 
safety of individuals, Quotient Sciences may take urgent safety measures before 
informing the Sponsor, but the Sponsor must be informed immediately after the hazard 
has resolved.  
The Sponsor is responsible for informing the appropriate regulatory authorities, and the 
EC; the task of reporting urgent safety measures will be delegated to Quotient Sciences. 
16.3 Reporting  
 Reporting Serious Adverse Events  
The Investigator must notify the study Sponsor and pharmacovigilance provider of any 
SAE or SAR immediately, and in all cases within 24 hours of becoming aware of the 
event or reaction. A copy of the written report of the event should promptly be sent to the 
study Sponsor for information purposes, in accordance with ICH guidelines for Good 
Clinical Practice (GCP) [12]. 
 Reporting of Suspected Unexpected Serious Adverse Reactions  
It is the responsibility of the Sponsor to determine whether a reported SAE fits the 
classification of a SUSAR and to notify the Investigator of their decision as soon as 
possible. 

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 Expedited Reporting of Events  
It is the responsibility of the Sponsor to determine whether an event requires expedited 
reporting and to notify the Investigator of their decision as soon as possible. 
Where expedited reporting is required, the following procedures should be followed. 
Fatal or life-threatening SUSARs 
It is the responsibility of the Sponsor to report fatal or life-threatening SUSARs to the 
MHRA as soon as possible, but no later than 7 calendar days after they first became 
aware of the reaction. Any additional relevant information should be sent within 8 days 
of the report. The task of reporting fatal or life-threatening SUSARs may be delegated to 
the pharmacovigilance provider. A separate notification to the EC is not required. 
Other SUSARs 
It is the responsibility of the Sponsor to report other SUSARs to the MHRA as soon as 
possible, but no later than 15 calendar days after they first became aware of the reaction. 
The task of reporting other SUSARs may be delegated to the pharmacovigilance 
provider. A separate notification to the EC is not required. 
 Reporting of Urgent Safety Measures  
Quotient Sciences is required to notify the MHRA and the EC of an urgent safety 
measure immediately by telephone and follow-up in writing within 3 calendar days from 
the date the measures are taken. 
 Reporting of COVID-19 Vaccine-Related Adverse Events  
AEs considered by the Investigator to be related to COVID-19 vaccines will be reported 
to the MHRA via the Yellow Card system. 
16.4 Serious Breaches  
It is the responsibility of the Sponsor to notify the MHRA of any serious breach, which is 
likely to affect, to a significant degree, the safety or mental integrity of the subjects of the 
study or the scientific value of the study.  
All serious breaches will be notified to the MHRA within 7 days. The reporting will be 
performed by the party who suspects the serious breach. 
17 Protocol Amendments and Deviations  
17.1 Amendments  
After the protocol has been submitted to the MHRA and EC, any amendment must be 
agreed by the Investigator after discussion with the Sponsor and will be formally 
documented. 
All substantial amendments will be submitted to the MHRA and/or EC for approval and/or 
an opinion, respectively, as required by current regulations. 
If the PIS and ICF are updated as a result of the substantial amendment, the new 
approved versions will be used to re-consent currently enrolled subjects and must be 
provided to newly enrolled subjects prior to their entry into the study. 

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17.2 Protocol Deviations  
The study must be conducted in accordance with the Clinical Protocol. Should a protocol 
deviation occur, it must be promptly assessed in order to decide whether any of these 
non-compliances should be reported to the MHRA as a serious breach of GCP and the 
Clinical Protocol. 
Protocol waivers are not acceptable. 
Deviations from the protocol will be recorded in the source as noted by the clinical staff. 
If necessary, the Sponsor will be informed of the deviation. 
Any protocol deviations assessed as major will be discussed with the Sponsor in order 
to determine if the withdrawal criteria stated in Section 8.3 have been met. 
18 Regulatory  
18.1 Compliance  
This study will be conducted in accordance with the protocol and with the following 
legislation: 
• 
ICH GCP Guidelines approved by the Committee for Medicinal Products for Human 
Use (CHMP) on 17 Jul 1996, which came into force on 17 Jan 1997, updated Jul 
2002, Integrated Addendum E6 (R2) dated 09 Nov 2016 [12]. 
• 
ICH E8 (R1) General Considerations for Clinical Studies, dated Oct 2021 [13]. 
• 
The Medicines for Human Use (Clinical Trials) Regulations. Statutory Instruments 
2004 No. 1031 [14]. 
• 
The Medicines for Human Use (Clinical Trials) Amendment Regulations. Statutory 
Instruments 2006 No. 1928 [15]. 
• 
The Medicines for Human Use (Clinical Trials) Amendment (No. 2) Regulations. 
Statutory Instruments 2006 No. 2984 [16]. 
• 
The Medicines for Human Use (Clinical Trials) Amendment Regulations. Statutory 
Instruments 2008 No. 941 [17]. 
• 
The Medicines for Human Use (Clinical Trials) (Amendment) (EU Exit) Regulations. 
Statutory Instruments 2019 No. 744 [18]. 
In addition, the study will be performed according to the ethical principles outlined in the 
World Medical Association Declaration of Helsinki and its amendments [19]. 
18.2 MHRA and Ethical Approval  
Prior to the initiation of the study, the clinical trial of an investigational medicinal product 
(CTIMP) application, the protocol and associated documentation must be approved by 
the MHRA and given a favourable opinion by an EC. A copy of this written approval and 
any correspondence with the MHRA and EC will be available at the clinical site and will 
be provided to the Sponsor.  
18.3 Source Data  
A study-specific source document identification list will be finalised with the Sponsor prior 
to the start of the clinical phase of the study. The document will identify what data should 
be considered source data for this study.  

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For this study, electronic data capture will be used where possible, and data will be 
automatically recorded into an eCRF. In instances where paper source documents are 
used, data to be transcribed into the eCRF will be identified using a Source Document 
Identification List, as governed by Quotient Sciences’ SOPs. 
18.4 Declaration of the End of the Study  
The end of the study is defined as the point at which the Sponsor determines that any 
remaining optional groups are not required to meet the objectives of the trial i.e., signed 
dose decision document or the completion of the last follow-up phone call/unscheduled 
follow-up visit for the final period, whichever occurs later. If the optional group is utilised, 
completion of the last follow-up phone call/unscheduled follow-up visit will be considered 
the end of the study. Any changes to this definition will be notified as a substantial 
amendment (see Section 17.1). 
The EC and MHRA should be notified of the conclusion of the study within 90 days of 
the end of the study, or within 15 days if the study is terminated early, clearly explaining 
the reasons for the termination. 
18.5 Document Storage and Archiving  
All documentation and correspondence pertaining to the study (source data, raw data, 
letters, etc.) will be kept in accordance with the ICH guidelines for GCP 1996, updated 
2002, Integrated Addendum E6 (R2) dated 09 Nov 2016 (ICH GCP Section 4.9.5) [12], 
The Medicines for Human Use (Clinical Trials) Regulations 2004 [14], The Medicines for 
Human Use (Clinical Trials) Amendment Regulations 2006 [15][16] and The Medicines 
for Human Use (Clinical Trials) (Amendment) (EU Exit) Regulations [18]. 
All study related documents will be retained for a minimum period of 25 years. After this 
time, the Sponsor will be contacted to ascertain whether continued storage or destruction 
is required in accordance with current regulations. 
18.6 Protection of Personal Data and Confidentiality  
Personal data are securely stored to prevent unauthorised access, disclosure, 
dissemination, alteration or loss of information and unauthorised personal data 
processing. Access to personal information is restricted so that only personnel who are 
required to access personal data as part of their job role can do so. All personnel who 
access personal information are bound by a duty of confidentiality. 
Technical arrangements surrounding the electronic storage and use of data are as 
follows: 
• 
Computers storing electronic personal data are protected by antivirus software and 
the network on which computers are linked are protected by industry grade firewalls. 
• 
Off-site personnel can only access networked computers through a virtual private 
network. 
• 
Electronic access of data is limited according to user roles. 
• 
All data are stored on password protected computers. 
Organisational arrangements are as follows: 
• 
All buildings are secured by key-card access. 

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• 
Manual files of personal data are stored within locked cabinets/restricted areas of the 
clinical unit that can only be accessed by authorised personnel. 
• 
Data security and/or confidentiality provisions are utilised in agreements with third 
parties. 
• 
Documented back-up and disaster recovery procedures are in place. 
• 
Internal audit and compliance functions provide regulatory oversight. 
The personal data of volunteers will be pseudonymised in that they will only include 
health, initials, date of birth and demographics (gender and ethnicity) and cannot be 
linked back to the individual by the recipient. The Sponsor shall be the data controller in 
respect of the personal data of the study subjects collected in connection with the study, 
and shall act in accordance with the relevant data protection laws in relation to the 
collection and processing of those personal data. The study subjects’ pseudonymised 
personal data shall be collected and processed for the purposes of the study, and may 
also be added to research databases and used in the future by the Sponsor and its 
affiliates for certain additional clinical research, for product regulation and safety 
reporting purposes and for ensuring compliance with legal requirements. The study 
subjects’ pseudonymised personal data may be processed for such purposes by other 
parties including: the Sponsor’s affiliates and licensing partners, its business partners, 
regulatory agencies and other health authorities, and ECs. The study subjects’ 
authorisation for such use and disclosure shall be obtained by the study subjects signing 
the ICF for the study. 
Additionally, Quotient Sciences personnel are contractually bound by a duty of 
confidentiality and receive training on this matter. 
18.7 Data Security Breach  
Quotient Sciences has a comprehensive process in place for identifying, assessing, 
resolving and reporting any potential data security breach. All staff are trained in the 
identification of potential data security breaches. Potential breaches are managed by 
appropriately trained quality assurance (QA) personnel in accordance with Quotient 
Sciences’ SOPs. After robust assessment of data breaches, those deemed serious will 
be reported to the Sponsor and Information Commissioner’s Office, as applicable. 
19 Quality Control and Quality Assurance  
QC of all data collected from this study will be performed in accordance with Quotient 
Sciences’ SOPs. This study (or elements thereof) may be subject to Quotient Sciences 
QA audit, in line with current internal auditing procedures. Similarly, the study (or 
elements thereof) may be subject to Sponsor QA audit. 
19.1 Monitoring  
GCP requires that studies are adequately monitored. The Sponsor should determine the 
appropriate extent and nature of monitoring. A study monitor, independent of Quotient 
Sciences, will be appointed to verify that the study is conducted in accordance with 
current GCP, regulatory requirements, the protocol and that the data are authentic, 
accurate and complete.  
The Investigator agrees to receive visits from a study monitor and provide assistance to 
verify protocol implementation, source completion and transcription of data into the 
eCRF, document storage and AE reporting. 

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Quotient Sciences will extend the professional privilege of access to the subjects’ clinical 
source documents to the study monitor, EC, regulatory bodies or other authorised 
personnel (e.g., auditor) for the purposes of source data verification. 
Following completion of the study both study related documents and subject data may 
be sent to the Sponsor at a location outside of the UK where data protection laws differ. 
In the interests of confidentiality, subjects will not be identified on any such documents 
or data, and specific subject consent for such a disposition will be obtained. 
20 Finance and Insurance  
The Sponsor (Melinta Therapeutics, LLC) has funded this study. A no-fault clinical trials 
insurance has been obtained by the Sponsor. The Sponsor insurance will compensate 
subjects in accordance with the Association of the British Pharmaceutical Industry 
Guidelines for Phase I Clinical Trials 2018 edition [10]. 
21 Publication  
Please refer to the Master Services Agreement for information on publication.  
Quotient Sciences shall have the right to publish the results of the research, subject to 
the Sponsor’s (Melinta and the Biomedical Advanced Research and Development 
Authority) prior written consent, which shall not be unreasonably withheld or delayed. 
Following the receipt of such consent, Quotient Sciences shall submit a copy of the 
proposed publication to the Sponsor, who shall have 45 calendar days for manuscripts 
and 30 calendar days for abstracts in which to request amendments thereto which, to 
the extent that such proposed amendments are reasonable, Quotient Sciences shall be 
obliged to incorporate prior to such publication. 
The Sponsor undertakes that, prior to publication of any information, article, paper, report 
or other material concerning the research, it will submit a copy of such publication to 
Quotient Sciences, who shall have 30 days in which to request amendments thereto 
which, to the extent that such proposed amendment are reasonable, the Sponsor shall 
be obliged to incorporate prior to such publication. All such publications shall 
acknowledge contract support as follows: “This project has been funded in whole or in 
part with Federal funds from the Department of Health and Human Services; Office of 
the Administration for Strategic Preparedness and Response; Biomedical Advanced 
Research and Development Authority, under Prime Contract No. 75A50123C00022". 
22 References  
[1] 
Melinta Therapeutics, LLC. Prescribing Information for Baxdela® (Delafloxacin). 
Revised Jun 2021. Available at: https://baxdela.com/docs/baxdela-prescribing-
information.pdf.  
[2] 
Electronic Medicines Compendium. Quofenix® 450 mg Tablets Summary of 
Product 
Characteristics. 
09 Jan 2024. 
Available 
at: 
https://www.medicines.org.uk/emc/product/11482/smpc.  
[3] 
US Department of Health and Human Services: Centers for Disease Control and 
Prevention. Antibiotic Resistance Threats in the United States. Dec 2019. 
Available 
at: 
https://www.cdc.gov/drugresistance/pdf/threats-report/2019-ar-
threats-report-508.pdf.  

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[4] 
Dryden MS. Skin and soft tissue infection: microbiology and epidemiology. Int J 
Antimicrob Agents. 2009; 34 Suppl1:S2-7. 
[5] 
Melinta Therapeutics, LLC. Investigator’s Brochure for Delafloxacin (Baxdela®). 
Edition 24.0, 11 Mar 2024. 
[6] 
FDA Guidance for Industry: Bioavailability Studies Submitted in INDs and NDAs 
– General Considerations. 2022. 
[7] 
EMA – Guidance on the investigation of bioequivalence. 20 Jan 2010. 
[8] 
Melinta Therapeutics, LLC. An intravenous infusion (1-hour) study of fertility and 
early embryonic development to implantation of RX-3341 in rats. Report 
WIL-880002. Jan 2014. 
[9] 
Heads of Medicines Agency: Clinical Trials Facilitation Group. Recommendations 
related to contraception and pregnancy testing in clinical trials. 21 Sep 2020. 
https://www.hma.eu/fileadmin/dateien/Human_Medicines/01-
About_HMA/Working_Groups/CTFG/2020_09_HMA_CTFG_Contraception_gui
dance_Version_1.1_updated.pdf.  
[10] 
Guidelines for Phase I Clinical Trials. Association of the British Pharmaceutical 
Industry Guidelines. London, UK; 2018 Edition (publication date 29 May 2018). 
[11] 
Peryam DR, and Pilgrim FJ. Hedonic scale method of measuring food 
preferences. Food Technology. 1957; 11: Suppl., 9-14. 
[12] 
ICH GCP Guidelines approved by the CHMP on 17 Jul 1996, which came into 
force on 17 Jan 1997, updated Jul 2002, Integrated Addendum E6 (R2) dated 
09 Nov 2016. 
[13] 
ICH E8 (R1) General Considerations for Clinical Studies, dated Oct 2021. 
[14] 
The Medicines for Human Use (Clinical Trials) Regulations. Statutory 
Instruments 2004 No. 1031. 
[15] 
The Medicines for Human Use (Clinical Trials) Amendment Regulations. 
Statutory Instruments 2006 No. 1928. 
[16] 
The Medicines for Human Use (Clinical Trials) Amendment (No. 2) Regulations. 
Statutory Instruments 2006 No. 2984. 
[17] 
The Medicines for Human Use (Clinical Trials) Amendment Regulations. 
Statutory Instruments 2008 No. 941. 
[18] 
The Medicines for Human Use (Clinical Trials) (Amendment) (EU Exit) 
Regulations. Statutory Instruments 2019 No. 744. 
[19] 
World Medical Association, Declaration of Helsinki. Ethical Principles for Medical 
Research Involving Human Subjects (and all subsequent amendments). 
 

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Appendix 1 
Clinical Laboratory Parameters  
Haematology 
Clinical Chemistry 
Virology 
Urinalysis 
Drugs of Abuse 
Haemoglobin 
Haematocrit (HCT; packed cell 
volume [PCV]) 
Red blood cell (RBC; 
erythrocyte) count 
Mean corpuscular volume 
(MCV) 
Mean corpuscular 
haemoglobin (MCH) 
Mean corpuscular 
haemoglobin concentration 
(MCHC) 
Platelet count 
White blood cell (WBC; 
leukocytes) count 
Neutrophils 
Lymphocytes 
Monocytes 
Eosinophils 
Basophils 
 
Sodium 
Potassium 
Chloride 
Bicarbonate 
Urea 
Creatinine 
Bilirubin (total) 
Bilirubin (direct; only if total is 
elevated) 
Alkaline phosphatase 
Aspartate aminotransferase 
(AST) 
ALT 
Creatine kinase (CK) 
Gamma glutamyl transferase 
(GGT) 
Protein (Total) 
Albumin 
Calcium 
Corrected calcium 
Glucose (fasting) 
Glucose 
FSH (post-menopausal female 
subjects only)  
Beta human chorionic 
gonadotropin (β-hCG) (all 
female subjects) 
Hepatitis B surface antigen 
Hepatitis C virus antibody 
HIV 1 & 2 antibodies 
 
If Required: 
SARS-CoV-2 antigen 
Bilirubin 
Urobilinogen 
Ketones 
Glucose 
Protein 
Blood 
Nitrites 
pH 
Specific gravity 
Leukocytes 
 
At discretion of Investigator 
based on urinalysis results 
Microbiology  
Urine microscopy 
 
Urine Pregnancy 
Human chorionic 
gonadotropin (hCG) (all 
female subjects) 
Amphetamines 
Barbiturates 
Benzodiazepines 
Cocaine 
Marijuana/cannabis 
Methadone 
Methamphetamine/ 
ecstasy 
Morphine/opiates 
Phencyclidine 
Tricyclic antidepressants 
 

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Appendix 2 
Schedule of Assessments  
Study Day 
-28 
to -2 
-1 
1 
2 
3 
6 ± 1 
FUP Phone Call 
or 
Unscheduled 
FUP Visitc 
Times After Dosing (h) 
 
S 
Aa 
P 
0 
0.5 
1 
1.5 
2 
3 
4 
6 
8 
10 
12 
14 
16 
20 
24 
48b 
General Assessments 
 
Informed Consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medical History 
X 
Xd 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Weight, Height and BMI 
X 
Xe 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Vein Assessment 
X 
Xf 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Drug Screen 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Alcohol Breath Test 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Carbon Monoxide Breath Test 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Randomisationg 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
IMP Administration 
 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Safety Assessments 
 
Physical Examination 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Targeted (symptom driven) 
Physical Examinationh 
 
Xf 
Xi 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
 
X 
Clinical Laboratory Testsj 
X 
Xf 
Xi 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
X 
Urinalysis 
X 
Xf 
Xi 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
 
Serum Pregnancy Testk 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Urine Pregnancy Testk 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
X 
Single 12-Lead ECGs 
X 
X 
X 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
X 
X 
X 
Vital Signsl 
X 
X 
X 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
X 
X  
X 
Adverse Events 
< ---------------------------------------------------------------------------------X--------------------------------------------------------------------------------- > 
Prior and Concomitant Medication  < ---------------------------------------------------------------------------------X--------------------------------------------------------------------------------- > 
PK Assessments 
 
Plasma Samples for Delafloxacin 
 
 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Taste/Palatability Assessments 
 
Taste/Palatability Questionnairem 
 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
A = admission, FUP = follow-up, P = pre-dose, S = screening  
If replacement subjects are required, they will undergo screening assessments as detailed above 
All assessments/procedures to be completed for every period unless specified otherwise 

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a Subjects will be admitted to the clinical unit in the morning on the day before dosing (Day -1) in Period 1, and in the evening on the day before dosing (Day -1) in 
Period 3 and optional Period 4. Subjects will remain resident in the clinical unit between Periods 1 and 2; therefore, no admission procedures will be conducted for 
Period 2 
b Discharge from the clinical unit (Periods 2 to 4 only). There will be a minimum washout of 4 days between dosing in Periods 1 and 2. In the event of early 
withdrawal, discharge assessments should be completed 
c A follow-up phone call will take place on Day 6 ± 1 of the final treatment period, to ensure the ongoing wellbeing of the subjects. If a subject reports any AEs that 
present a cause for concern, they will be required to attend the clinical unit for a (unscheduled) follow-up visit. Assessments may be performed at the unscheduled 
follow-up visit as indicated 
d Update only 
e Weight only 
f Period 1 only 
g Subjects will be randomised immediately prior to dosing in Period 1, for allocation of regimens across Periods 1 and 2 
h Targeted (symptom driven) physical examination of the relevant body system(s) as clinically indicated, as per the Investigator’s judgement 
i Periods 2 to 4 only 
j Haematology and clinical chemistry at each time point including virology and FSH (post-menopausal female subjects only) at screening 
k All female subjects 
l Blood pressure, heart rate, oral temperature and respiratory rate will be measured at each time point 
m The taste/palatability questionnaire will be started within 10 minutes of each delafloxacin Powder for Oral Suspension (i.e., test) regimen administration. See 
Appendix 3 for details of the taste/palatability questionnaire 
 

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Appendix 3 
Example Taste/Palatability Questionnaire  
QSC300553 (ML-DEL-101-3727-1) Taste Questionnaire 
 
Study Period:  
 
Regimen:  
 
Subject Number:  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Subject Initials:  
 
 
Start time:  
 
  
 
 
 
 
 
 
 
 
 
 
(to be started within 10 minutes of dosing) 
 
Date:  
 
  
 
 
  
 
 
 
Question 1 
All aspects considered (smell, sweetness, bitterness, flavour, mouthfeel/texture, grittiness, and aftertaste), how would you rate your overall liking of this 
product:  
NOTE: Tick 1 box below in blue or black pen 
Question 2 
We want to know how much you like certain aspects of the product: smell, sweetness, bitterness, flavour, mouthfeel/texture, grittiness, and aftertaste. 
Please rate each test product independently of any previous taste questionnaires. NOTE: Tick 1 box in the row for each aspect 
 
Dislike 
extremely 
Dislike very 
much 
Dislike 
moderately 
Dislike 
slightly 
Neither like 
nor dislike 
Like slightly 
Like 
moderately 
Like very 
much 
Like 
extremely 
Not 
detectable 
Smell 
 
 
 
 
 
 
 
 
 
 
Sweetness 
 
 
 
 
 
 
 
 
 
 
Bitterness 
 
 
 
 
 
 
 
 
 
 
Flavour 
 
 
 
 
 
 
 
 
 
 
Mouthfeel/texture 
 
 
 
 
 
 
 
 
 
 
Grittiness 
 
 
 
 
 
 
 
 
 
 
Aftertaste 
 
 
 
 
 
 
 
 
 
 
Entered into eCRF by (initials): 
 
Date: 
 
QC checked by (initials): 
 
Date: 
 
 
Dislike 
extremely 
Dislike very 
much 
Dislike 
moderately 
Dislike slightly 
Neither like nor 
dislike 
Like slightly 
Like 
moderately 
Like very much 
Like extremely 
 
 
 
 
 
 
 
 
 
 

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Appendix 4 
Breakfast Content  
Meal Description 
Total 
Energy 
(kcal) 
Energy 
from Fat (%) 
Composition 
High-Fat Breakfast 
(FDA approved)a 
950 
58 
1 (40 g) hash brown, 2 (80 g) Unsmoked Rind less Streaky Bacon, 1 medium (45 g) egg fried in 
10 g of unsalted butter, 2 slices (95 g) of white sliced bread with 20 g of unsalted butter, 240 mL 
of full fat milk 
Values/content are approximate. Every effort will be made to include the items described above; however, items may be replaced as long as they contain the 
equivalent nutritional content as the item it has replaced 
a For FDA high-fat breakfast, if a replacement item is required it will be of comparable content, volume and viscosity 
 

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Appendix 5 
Protocol Amendment Summary of Changes  
This is the original protocol; no amendments have been performed to date. 

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Signatures for Quotient Sciences 
CONFIDENTIALITY AND GCP COMPLIANCE STATEMENT 
I confirm that I have read and that I understand this protocol, the Investigator’s Brochure, 
and any other product information provided by the Sponsor. I agree to conduct this study 
in accordance with the requirements of this protocol and also protect the rights, safety, 
privacy, and well-being of study subjects in accordance with the following: 
• 
The ethical principles that have their origin in the Declaration of Helsinki. 
• 
International 
Council 
for 
Harmonisation 
of 
Technical 
Requirements 
for 
Pharmaceuticals for Human Use E6 (R2) GCP: Consolidated Guideline. 
• 
All applicable laws and regulations, including, without limitation, data privacy laws 
and regulations. 
• 
Regulatory requirements for reporting serious adverse events defined in Section 16.3 
of this protocol. 
Information taken from the study protocol may not be disseminated or discussed with a 
third party without the express consent of the Sponsor.  
 
See electronic signature at the end of the 
document 
Principal Investigator 
Signature 
, UK 
 
 
 
Date 
 
 

Document Approvals
Approved Date: 22 Mar 2024
Document Author(s):  
 
Approval Task
Verdict:  Approve
Approval
22-Mar-2024 16:34:46 GMT+0000
Number: DOC-174016               Version: 1.0               Status: Approved    Approved Date: 22 Mar 2024
QSC300553 Clinical Protocol
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