A Phase 3, Randomized, Double-Blind, Double-Dummy Study to Compare the Efficacy and Safety of Oral Lefamulin (BC 3781) Versus Oral Moxifloxacin in Adults With Community-Acquired Bacterial Pneumonia
Phase: PHASE3
Conditions: Community Acquired Pneumonia
Sponsor: Nabriva Therapeutics AG

Nabriva Therapeutics AG 
Clinical Protocol NAB-BC-3781-3102 
 
 
V3.0:  17-Mar-2016 
Page 1 of 102 
Confidential Information 
 
 
 
 
 
 
 
 
 
Clinical Protocol No. NAB-BC-3781-3102 
 
 
A Phase 3, Randomized, Double-Blind, Double-Dummy Study to Compare 
the Efficacy and Safety of Oral Lefamulin (BC-3781) Versus Oral 
Moxifloxacin in Adults With Community-Acquired Bacterial Pneumonia 
 
 
US IND 125546 (Oral) 
 
EudraCT Number 2015-004782-92 
 
 
 
 
 
 
 
Protocol Status 
Version 
Date 
Original 
1.0 
21-Dec-2015 
Amendment 1 
2.0 
17-Feb-2016 
Amendment 2 
3.0 
17-Mar-2016 
 
 
 
 
 
 
 
 
 
The information contained herein is the property of Nabriva Therapeutics AG and may not be 
produced, published, or disclosed to others without written authorization of Nabriva 
Therapeutics AG. 
 

Nabriva Therapeutics AG 
Clinical Protocol NAB-BC-3781-3102 
 
 
V3.0:  17-Mar-2016 
Page 2 of 102 
Confidential Information 
SPONSOR RELATED CONTACT DETAILS 
A Phase 3, Randomized, Double-Blind, Double-Dummy Study to Compare the Efficacy 
and Safety of Oral Lefamulin (BC-3781) Versus Oral Moxifloxacin in Adults With 
Community-Acquired Bacterial Pneumonia 
(Protocol NAB-BC-3781-3102 with Amendments 1 and 2) 
Sponsor: 
Nabriva Therapeutics AG 
Leberstraße 20 
1110 Vienna 
Austria 
Sponsor’s Study Managers: 
Patricia Spera, PhD 
Nabriva Therapeutics US, Inc. 
1000 Continental Drive, Suite 600 
King of Prussia, PA  19406 
USA 
Tel:  +1 610 816 6656 
Cell: +1 610 209 5574 
Email: patricia.spera@nabriva.com 
 
Claudia Lell, PhD 
Nabriva Therapeutics AG 
Leberstraße 20 
1110 Vienna 
Austria 
Tel:  +43 1 74093 1242 
Cell:  +43 664 9631469 
Email:  claudia.lell@nabriva.com 
Sponsor’s Medical Officer: 
 
Leanne Gasink, MD 
Senior Director, Clinical Development and Medical Affairs 
Nabriva Therapeutics AG  
Nabriva Therapeutics US, Inc. 
1000 Continental Drive, Suite 600 
King of Prussia, PA  19406 
USA 
Tel:  +1 610 816 6658 
Cell:  +1 215 880 6689 
Email: leanne.gasink@nabriva.com 
Covance’s Medical Officer: 
Norberto E. Soto, MD 
Senior Medical Director 
Clinical Development Services  
Covance, Inc. 
206 Carnegie Center 
Princeton, NJ  08540 
USA 
Tel:  +1 609 419 2529 
Cell:  +1 609 216 2430 
RightFax: +1 609 419 2803 
Email:  Norberto.Soto@Covance.com 
 

Nabriva Therapeutics AG 
Clinical Protocol NAB-BC-3781-3102 
 
 
V3.0:  17-Mar-2016 
Page 4 of 102 
Confidential Information 
INVESTIGATOR SIGNATURE PAGE 
A Phase 3, Randomized, Double-Blind, Double-Dummy Study to Compare the Efficacy 
and Safety of Oral Lefamulin (BC-3781) Versus Oral Moxifloxacin in Adults With 
Community-Acquired Bacterial Pneumonia 
(Protocol NAB-BC-3781-3102 with Amendments 1 and 2) 
In conducting this clinical study, I agree to be responsible for: 
• Ensuring that the clinical investigation is conducted according to the World Medical 
Association Declaration of Helsinki in its revised edition (Fortaleza, Brazil, October 
2013), the guidelines of International Conference on Harmonization (ICH) Good Clinical 
Practice (GCP) (CPMP/ICH/135/95), the signed Form Food and Drug Administration 
(FDA) 1572 Statement of Investigator (applies to all studies conducted under a United 
States Investigational New Drug Application) and other applicable local and national 
laws and requirements. 
• Protecting the rights, safety, and welfare of subjects under my care. 
• Maintaining control of the drugs under investigation. 
I also agree to conduct the study as detailed in the protocol and in accordance with Nabriva 
Therapeutics AG guidelines and all applicable government regulations.  These guidelines and 
regulations include, but are not limited to: 
• Permission to allow Nabriva Therapeutics AG and regulatory agencies to inspect study 
facilities and pertinent records at reasonable times and in a reasonable manner, which 
ensures subject confidentiality.  If I am notified that this study is to be inspected by a 
regulatory agency, I will notify Nabriva Therapeutics AG as soon as possible thereafter 
(no later than 1 week). 
• Submission of the proposed clinical investigation, including the protocol, the informed 
consent documents, and any other subject materials required for study conduct, to a duly 
constituted Independent Ethics Committee (IEC)/Institutional Review Board (IRB) for 
approval, and acquisition of written approval for each, prior to the use of the study drug. 
• Obtaining written informed consent only after ensuring that the subject, or his/her legal 
representative, is competent to make the decision, understands what is contained in the 
informed consent document, and is consenting voluntarily.  Written informed consent 
will be obtained prior to administration of study drug or any non-routine study-related 
procedures; the document contains all the essential elements of consent and has been 
previously approved by the sponsor and IEC/IRB.  Reference of written informed consent 
will be provided in source documentation. 
• Submission of any protocol amendment to the IEC/IRB.  If the protocol amendment 
change(s) increase risk to the study population, full IEC/IRB written approval must be 
obtained prior to implementation.  For changes that do not involve increased risk or affect 
the validity of the investigation or the subject's rights, prior IEC/IRB approval may be 
obtained by expedited review. 

Nabriva Therapeutics AG 
Clinical Protocol NAB-BC-3781-3102 
 
 
V3.0:  17-Mar-2016 
Page 5 of 102 
Confidential Information 
• Adherence to the study protocol.  Documentation and explanation of individual post-
enrollment protocol deviations will be recorded in the source documentation at the site 
and be provided to Nabriva Therapeutics AG. 
• Notification to Nabriva Therapeutics AG of all serious adverse events, regardless of 
relationship to study drug, as specified in the protocol.  Notification to the IEC/IRB of 
serious adverse events as specified in the protocol and per additional guidelines as 
provided by the IEC/IRB. 
• Notification to IEC/IRB of all unanticipated problems within the timeframe provided by 
the IEC/IRB.  For the purposes of this study, unanticipated problems are defined as any 
incident, experience, or subject outcome that meets all of the following criteria: (1) 
unexpected; (2) related or possibly related to participation in the study; (3) and suggests 
that the research places subjects or others at a greater risk of harm (including physical, 
psychological, economic, or social harm) than was previously known. 
• Provision of adequate study oversight by personally conducting or supervising the 
investigation, including, but not limited to: allotting sufficient time to properly conduct 
and complete the study within the agreed upon time period; having available an adequate 
number of qualified staff and adequate facilities for the expected duration of the study 
and to conduct the study properly and safely; and ensuring that all persons assisting with 
the study are adequately informed about the protocol and the investigational product(s) 
and are capable of performing their study-related duties and functions.  Qualifications of 
individuals assigned responsibility for the administration of the investigational product 
will be compliant with state and local law or national regulations, as applicable. 
• Submission of timely progress reports to the IEC/IRB and Nabriva Therapeutics AG at 
appropriate intervals not to exceed 1 year and submission of a final report to the IEC/IRB 
within the timeframe set by the IEC/IRB, but not later than 3 months after the completion 
or termination of the clinical investigation.  
• Maintenance of accurate source records from which case report forms are completed as 
well as drug accountability records that show the receipt and disposition (on an overall 
and per subject basis) of all study drug(s) shipped to the investigator by Nabriva 
Therapeutics AG. 
In addition, I agree to provide all the information requested in the eCRF presented to me by 
Nabriva Therapeutics AG by carefully following the completion guidelines provided as part 
of the eCRF. 
If I opt to terminate my participation in the study, the foregoing shall equally apply. 
 
 
 
 
Investigator’s Name (Please Print) 
 
 
 
 
 
Investigator’s Signature 
 
Date 
 

Nabriva Therapeutics AG 
Clinical Protocol NAB-BC-3781-3102 
 
 
V3.0:  17-Mar-2016 
Page 6 of 102 
Confidential Information 
AMENDMENT 2:  17-MAR-2016 
Amendment 2 addresses an inconsistency within the protocol.  In accordance with Appendix 
4 to the protocol, the use of strong P-glycoprotein inhibitors during study participation is 
prohibited.  Thus, progesterone-containing products (such as oral contraceptives) are 
prohibited.  In addition to revising the inclusion criterion associated with use of oral 
contraceptives, wording was added to the prohibited medications section for emphasis.  
These changes were made to the study synopsis, as applicable.  Added text is bolded; deleted 
text is struck through.   
Section 4.1 − Inclusion Criteria 
#8 If female, meets the following criteria: 
• 
Surgically sterile or ≥2 years postmenopausal, or if of childbearing potential (including being 
<2 years postmenopausal), has a negative pregnancy test, and if participating in sexual 
activity that may lead to pregnancy, agrees to use an effective dual method of contraception 
(e.g., condom plus diaphragm, condom plus spermicide, intrauterine device plus spermicide, 
oral contraceptive plus condom) during the study and for ≥28 days after the last dose of study 
drug.  If a male partner has been surgically sterile for ≥1 year, a single contraception method 
may be used.  NOTE:  The use of contraceptives containing progesterone is not 
permitted. 
Section 6.9 – Prohibited Medications 
Bullet #6 
• 
Strong p-glycoprotein inhibitors (see Appendix 4) [NOTE:  The use of contraceptives 
containing progesterone is not permitted.] 
 
AMENDMENT 1:  17-FEB-2016 
Amendment 1 addresses revisions to the protocol requested by the US Food and Drug 
Administration (FDA) at the Type C Meeting held on 27-Jan-2016 with respect to the non-
inferiority (NI) margin.  The change in NI margin resulted in the change of other statistical 
parameters including the randomization ratio and sample size.   
In addition, FDA requested (1) an increase in the number of subjects with a PORT Risk Class 
of III or IV; (2) methicillin-resistant Staphylococcus aureus (MRSA) be added to the list of 
pathogens that would exclude study eligibility; and (3) an increase in the number of 
pharmacokinetic sampling time points (i.e., the 8-9 h PK time point, which was previously 
optional for all subjects, is now required for inpatients and optional for outpatients).  An 
increase in the number of subjects with PORT Risk Class III or IV resulted in a change of the 
outcome rates used for determination of the sample size.  
These revisions were made to the protocol sections noted below as well as to the study 
synopsis and the Schedule of Assessments and Procedures (Table 1).  Added text is bolded; 
deleted text is struck through. 

Nabriva Therapeutics AG 
Clinical Protocol NAB-BC-3781-3102 
 
 
V3.0:  17-Mar-2016 
Page 7 of 102 
Confidential Information 
Section 3 – STUDY DESIGN 
Paragraph 1, Sentences 2 & 3:  The planned enrollment is 573 738 subjects (382 369 subjects 
in the lefamulin group and 191 369 subjects in the moxifloxacin group) with PORT Risk 
Class II, III, or IV.  Eligible subjects will be randomized 2 1:1 to lefamulin or moxifloxacin, 
using an interactive response technology (IRT).   
Section 4.2 – Exclusion Criteria 
Exclusion criterion #4:  Have confirmed or suspected CABP caused by a pathogen known to 
be resistant to any of the study drugs (e.g., MRSA, Pseudomonas aeruginosa, any pathogen 
of the Enterobacteriaceae Family) or attributable to etiologies other than 
community-acquired bacterial pathogens (e.g., ventilator-associated pneumonia, 
hospital-acquired bacterial pneumonia, bacterial aspiration pneumonia, Pneumocystis jiroveci 
pneumonia or other fungal pneumonia, viral or mycobacterial infection of the lung). 
Section 5.3 – Randomization 
Paragraph 1, Sentence 1:  Qualified subjects will be randomized to receive lefamulin or 
moxifloxacin in a 2 1:1 allocation ratio.   
Paragraph 2, Sentence 3:  A minimum of 25 50% of the total number of subjects randomized 
will have a PORT Risk Class of III or IV. 
Section 6.14 – Sample Collection for Pharmacokinetic Analysis 
Footnote “c” has been added to Table 5 (Sample Collection Time Points for the 
Determination of Lefamulin Plasma Concentrations following Oral Administration) in 
reference to the 8-9 h PK collection time point after the first dose of study drug, as follows: 
c: The 8-9h sample is required for inpatients.  The 8-9 h sample is optional for outpatients; 
however, should be obtained if logistically feasible. 
Section 9.2 – Sample Size Determination 
A total of 573 738 subjects will be randomized in a ratio of 21:1 (lefamulin:moxifloxacin) 
resulting in 382 369 subjects in the lefamulin arm and 191 369 in the moxifloxacin arm in 
this study.  The total number of subjects included in this study is sufficient to achieve the 
primary and secondary study objectives based on statistical considerations. 
Retrospective analyses of clinical study data for patients with CABP of varying severity as 
well as 2 recent clinical trials in CABP indicate the point estimates for an ECR responder at 
Days 3-5 range from 72% to 81% (FDA, 2011; Cempra, 2015a Barrera et al., 2016; 
Cempra, 2015b; Oldach et al., 2015).  Thus, it is reasonable to assume that in a prospective 
study of subjects with CABP, the proportion of subjects who are responders for ECR at 
96 ± 24 hours post first dose of study drug will be approximately 77 79%.   
The primary efficacy analysis variables used for NI analyses for the Marketing Authorization 
Application (MAA) to the EMA will be the proportion of subjects with an IACR of Success 
at TOC in the mITT and CE-TOC Analysis Sets.  In recent clinical studies, IACR success 
rates at the TOC Visit in the CE Analysis Set ranged from 77% to 93% (Cempra, 2015b) and 
in the ITT Analysis Set ranged from 85% to 89% depending on the antibiotics under study 
and the severity of the CABP.  Based on these data, an 87 85% IACR success rate in the CE-
TOC Analysis Set was chosen for determination of the sample size.  The success rate is 

Nabriva Therapeutics AG 
Clinical Protocol NAB-BC-3781-3102 
 
 
V3.0:  17-Mar-2016 
Page 8 of 102 
Confidential Information 
expected to be about 5% lower in the mITT Analysis set.  It is expected that <1% of subjects 
will be excluded from the mITT Analysis Set and thus, the sample size determination 
assumes the same number of subjects in the ITT and mITT Analysis Sets. 
Utilizing an anticipated ECR responder rate of 77 79% in the ITT Analysis Set, a 2 1:1 
randomization ratio, a two-sided alpha of 0.025, and a continuity corrected Z-test with 
unpooled variance, a sample size of 573 738 subjects (382 369 subjects in the lefamulin 
group and 191 369 in the moxifloxacin group) provides 90% power to establish the NI of 
lefamulin to moxifloxacin for ECR using a NI margin of 12.5 10.0% at the ECA.  Assuming 
an IACR success of 82 80% and 87 85% in the mITT and CE-TOC Analysis Sets, 
respectively, and a clinical evaluability rate of 80%, there is 80 91% power for demonstration 
of NI for IACR at the TOC Visit using a 10% NI margin. 
The calculated power in each analysis set for the primary and secondary outcomes is 
provided in Table 6 below. 
Table 6. 
Power Calculations for the Primary and Secondary Efficacy 
Outcomes 
 
Primary Outcome (FDA) 
(ECR 96 ± 24 hours After the First 
Dose of Study Drug) 
Secondary Outcome  
(Investigator’s Assessment of Clinical Response 
at TOC- Primary for EMA) 
Analysis Set 
ITT 
mITT 
CE-TOC 
NI Margin 
12.5 10% 
10% 
10% 
N 
573 738 (382:191 369:369) 
573 738 
459 590 
Outcome Rate 
77 79% 
82 80% 
87 85% 
Evaluability Rate 
NA 
NA 
80% 
Power 
90% 
80 91 % 
81 91% 
CE = clinically evaluable; ITT = intent to treat; mITT = modified ITT; TOC = test of cure 
Section 9.4.4 – Pharmacokinetic Analysis Variables 
Paragraph 1, Sentence 3:  Individual AUC values from Day 1 and Day 4 [i.e., 96  ±  24 hours 
post first dose] (collected pre-dose, 1-2 h post dose and 3-4 h post dose, and an optional time 
point at 8-9 h post dose [8-9 h post dose is required for inpatients; optional for 
outpatients]) will be used for the PK/PD analysis.   
Section 9.6.1 – Primary Efficacy Analysis 
Paragraph 3, Sentence 4:  If the lower limit of the 95 % CI for the difference in responder 
rates in the ITT Analysis Set is greater than -12.5% -10.0 %, the null hypothesis will be 
rejected and the NI of lefamulin to moxifloxacin will be concluded.   
In addition, the Sponsor has made the following revisions to the original protocol to provide 
clarity and to align this protocol with the Phase 3 IV/Oral Protocol (NAB-BC-3781-3101) for 
the treatment of CABP.  These changes will assist in statistical analysis at the time of 
submission for marketing approval.  These revisions were made to the protocol sections 
noted below as well as to the study synopsis and the Schedule of Assessments and 
Procedures (Table 1). Added text is bolded; deleted text is struck through.  None of these 
changes are expected to affect subject safety or the interpretation of study results. 

Nabriva Therapeutics AG 
Clinical Protocol NAB-BC-3781-3102 
 
 
V3.0:  17-Mar-2016 
Page 9 of 102 
Confidential Information 
Section 6.5 – Vital Signs and Oxygen Saturation 
[Rationale: Collection of supplemental oxygen therapy data has been added to the protocol 
and eCRF.]  
New paragraph (Paragraph 2) was added: 
In addition, if the subject is receiving supplemental oxygen therapy, the amount given 
will be recorded in the eCRF. 
Section 6.7 – Arterial Blood Gases 
[Rationale:  FiO2 is not being collected on the eCRF as part of the results of arterial blood 
gases.] 
Study sites are not required to measure arterial blood gases (PaO2, PaCO2) (and FiO2) or pH.  
However, if these data are available, they should be recorded in the eCRF.   
Section 6.15.8 – Nasopharyngeal Specimen 
[Rationale:  All S. pneumoniae will be tested.  H. influenzae testing will depend on validation 
of procedures using samples collected early in the trial.  It is possible that only some subjects 
will have testing for H. influenzae performed.] 
Paragraph 1, Sentences 1 and 2:  A nasopharyngeal specimen (1 swab) will be obtained at 
Screening and sent to the central laboratory/specialty laboratory for S. pneumoniae and H. 
influenzae culture, susceptibility testing, as well as identification by PCR.  Culture, 
susceptibility testing, as well as identification by PCR, may also be performed for 
H. influenzae.   
Section 7.5 – Other Reportable Events 
[Rationale:  All subjects who meet the criteria for potential Hy’s Law, regardless of whether 
it is an SAE, will complete the Hy’s Law eCRF.] 
• Potential Hy’s Law (PHL) [Sentences 1 and 2] 
The investigator is responsible for prompt reporting of any patients who has had both (1) 
AST or ALT > 3 x ULN and (2) total bilirubin > 2 x ULN at any point in the study (i.e., 
meets criteria for Potential Hy’s Law), unless the event is already reported as an SAE.  The 
investigator must complete the Hy’s Law eCRF.   
Section 9.4.4 – Pharmacokinetic Analysis Variables 
[Rationale:  PK analysis will include lefamulin’s main metabolite, BC-8041; also edits made 
to popPK anlaysis.] 
Paragraph 1, Sentence 2:  Calculated PK will enable descriptive statistical analysis of PK 
variables such as the maximum observed drug concentration (Cmax) and area under the 
concentration-time curve (AUC) for lefamulin and its main metabolite, BC-8041.   
Paragraph 1, Sentence 4: The population PK analysis based on population PK as well as a 
PK/PD analysis will be reported separately. 

Nabriva Therapeutics AG 
Clinical Protocol NAB-BC-3781-3102 
 
 
V3.0:  17-Mar-2016 
Page 10 of 102 
Confidential Information 
Section 9.4.5 – Other Variables 
[Rationale: A description of the disk inhibition zone diameter which would qualify as 
development of decreasing susceptibility is provided.]  
• Development of Decreasing Susceptibility: Increase in MIC (≥ 4x) or 6 mm decrease 
from baseline in disk inhibition zone diameter to the study drug received for a 
pathogen isolated at baseline and subsequently isolated from a blood or lower respiratory 
tract specimen. 
Section 9.7 – Safety Analyses 
[Rationale:  Across the lefamulin clinical development program, corrected QT interval will 
be summarized using the Frederica formula only.]  
Paragraph 5, Sentence 1:  Change from baseline to each scheduled evaluation and the overall 
worst post-baseline for RR interval, PR interval, QRS interval, QT interval, QT interval 
corrected with Bazzett, and QT interval corrected with Fridericia from the ECG will be 
summarized for each treatment group with the mean, standard deviation, minimum value, 
and maximum value. 
Section 19 - List of References 
Zeitlinger et al, 2014 (poster presentation) has been published in J Antimicrob Chemother.  
Reference and citations throughout the protocol have been updated to Zeitlinger et al, 2016. 
Cempra, 2015a (press release) has been published in Lancet.  Reference and citations 
throughout protocol have been updated to Barrera et al., 2016.  [Cempra, 2015b is now 
referenced and cited as Cempra, 2015.] 
In addition, the Sponsor has made correction of typographical errors (e.g., definition of ELF), 
updated information (e.g., increase in number of clinical isolates tested [Section 1.3, 
Paragraph 3, Sentence 1:  >13,400 vs. 13,600]), and consistency in formatting. 

Nabriva Therapeutics AG 
Clinical Protocol NAB-BC-3781-3102 
 
 
V3.0:  17-Mar-2016 
Page 11 of 102 
Confidential Information 
SYNOPSIS 
Study Title:  A Phase 3, Randomized, Double-Blind, Double-Dummy Study to Compare the 
Efficacy and Safety of Oral Lefamulin (BC-3781) Versus Oral Moxifloxacin in Adults With 
Community-Acquired Bacterial Pneumonia (Protocol NAB-BC-3781-3102 with 
Amendments 1 and 2). 
Study Objectives: 
Primary Objectives 
• Demonstrate the non-inferiority (NI) of lefamulin versus comparator with respect to the 
Early Clinical Response (96 ± 24 hours after the first dose of study drug) in the 
Intent-to-Treat (ITT) Analysis Set (FDA endpoint). 
• Demonstrate the NI of lefamulin versus comparator with respect to the Investigator’s 
Assessment of Clinical Response at Test of Cure (TOC) (i.e., 5-10 days after the last dose 
of study drug) in the modified-ITT (mITT) and Clinically Evaluable at TOC (CE-TOC) 
Analysis Sets (EMA endpoint). 
Secondary Objectives 
• Evaluate the Early Clinical Response in the Microbiological Intent-to-Treat (microITT) 
Analysis Set.   
• Evaluate the Investigator’s Assessment of Clinical Response at TOC in the microITT and 
Microbiologically Evaluable at TOC (ME-TOC) Analysis Sets. 
• Evaluate the By-Pathogen Microbiologic Response at TOC in the microITT and ME-
TOC Analysis Sets. 
• Evaluate the safety and tolerability of lefamulin versus comparator in the Safety Analysis 
Set. 
• Evaluate 28 day all-cause mortality in the ITT Analysis Set. 
Additional Objectives 
• Evaluate the Early Clinical Response by baseline pathogen in the microITT Analysis Set. 
• Evaluate the Investigator’s Assessment of Clinical Response at the End of Treatment 
(EOT) (i.e., within 2 days after the last dose of study drug) and at LFU in the mITT and 
CE Analysis Sets (CE-EOT for IACR at EOT and CE-LFU for IACR at LFU). 
• Evaluate the Investigator’s Assessment of Clinical Response by baseline pathogen at 
TOC and LFU in the microITT and ME- Analysis Sets (ME-TOC for IACR at TOC and 
ME-LFU for IACR at LFU). 
• Evaluate the By-Subject Microbiologic Response at TOC in the microITT and ME-TOC 
Analysis Sets. 
• Evaluate the Early Clinical Response PLUS improvement in vital signs in the ITT 
Analysis Set. 

Nabriva Therapeutics AG 
Clinical Protocol NAB-BC-3781-3102 
 
 
V3.0:  17-Mar-2016 
Page 12 of 102 
Confidential Information 
• Evaluate the plasma pharmacokinetics (PK) of lefamulin and its main metabolite, 
BC-8041, in the PK Analysis Set. 
• Explore a variety of health utilization variables and an investigational patient reported 
outcome (PRO) measure in subjects receiving lefamulin compared with subjects 
receiving comparator. 
Study Population: 
Inclusion Criteria   
Each subject must: 
1. Be male or female ≥ 18 years of age. 
2. Provide written informed consent and be willing and able to adhere to the study-specified 
procedures and restrictions.  NOTE:  Consent may be provided by the subject’s legally 
authorized representative in accordance with local regulations. 
3. Have an acute illness (≤ 7 days duration) with at least 3 of the following symptoms 
consistent with a lower respiratory tract infection (new or worsening): 
• Dyspnea. 
• New or increased cough. 
• Purulent sputum production. 
• Chest pain due to pneumonia. 
4. Have at least 2 of the following vital sign abnormalities:  
• Fever (body temperature > 38.0 °C (100.4 °F) measured orally or equivalent 
temperature from an alternate body site) or hypothermia (body temperature < 35.0 °C 
(95.0 °F) measured orally or equivalent temperature from an alternate body site). 
• Hypotension (systolic blood pressure < 90 mmHg). 
• Tachycardia (heart rate > 100 beats/min). 
• Tachypnea (respiratory rate > 20 breaths/min). 
5. Have at least 1 other clinical sign or laboratory finding of CABP: 
• Hypoxemia (i.e., O2 saturation < 90 % on room air or while receiving supplemental 
oxygen at subject’s baseline requirement or PaO2 < 60 mmHg). 
• Auscultatory and/or percussion findings consistent with pneumonia (e.g., crackles, 
egophony, dullness). 
• White blood cell (WBC) count > 10 000 cells/mm3 or < 4 500 cells/mm3 or > 15 % 
immature neutrophils (bands) regardless of total WBC count. 
6. Have radiographically-documented pneumonia within 48 hours before enrollment (i.e., 
infiltrates in a lobar or multilobar distribution or diffuse opacities on chest x-ray 
consistent with acute bacterial pneumonia).  NOTE: if a chest computed tomography scan 

Nabriva Therapeutics AG 
Clinical Protocol NAB-BC-3781-3102 
 
 
V3.0:  17-Mar-2016 
Page 13 of 102 
Confidential Information 
has been performed within 48 hours of enrollment and demonstrates findings consistent 
with pneumonia, it can be used in place of a chest x-ray. 
7. Have a Pneumonia Outcomes Research Team (PORT) Risk Class of II, III, or IV and be 
an appropriate candidate for oral antibiotic therapy as treatment for the current episode of 
CABP. 
8. If female, meets the following criteria: 
• Surgically sterile or ≥ 2 years postmenopausal, or if of childbearing potential 
(including being < 2 years postmenopausal), has a negative pregnancy test, and if 
participating in sexual activity that may lead to pregnancy, agrees to use an effective 
dual method of contraception (e.g., condom plus diaphragm, condom plus spermicide, 
intrauterine device plus spermicide) during the study and for ≥ 28 days after the last 
dose of study drug.  If a male partner has been surgically sterile for ≥ 1 year, a single 
contraception method may be used.  NOTE:  The use of contraceptives containing 
progesterone is not permitted. 
• Agrees not to breastfeed during the study and through ≥ 28 days after the last dose of 
study drug. 
9. If male, meets the following criteria: 
• If not surgically sterile and if participating in sexual activity that may lead to 
pregnancy, agrees to use an effective dual method of contraception (e.g., condom plus 
diaphragm, condom plus spermicide, intrauterine device plus spermicide, oral 
contraceptive plus condom) during the study and through ≥ 28 days after the last dose 
of study drug.  If surgically sterile for ≥ 1 year, a single contraception method may be 
used. 
Exclusion Criteria   
Each subject must NOT: 
1. Have received more than a single dose of a short-acting oral or IV antibacterial for CABP 
within 72 hours before randomization (See Appendix 2). 
• EXCEPTION:  Subjects who have received >48 hours of prior systemic antibacterial 
therapy for the current episode of CABP with unequivocal clinical evidence of 
treatment failure (i.e., worsening signs and symptoms) and isolation of an organism 
from blood or respiratory tract that is resistant to the prior systemic antibacterial 
therapy provided the organism is not resistant is to fluoroquinolones. 
2. Require concomitant systemic antibacterial therapy potentially effective against CABP 
pathogens (See Section 6.9). 
3. Have been hospitalized for 2 or more days within 90 days prior to the onset of symptoms 
or have resided in a nursing home or long-term healthcare facility within 30 days prior to 
the onset of symptoms.  NOTE:  Residence in an independent living facility is permitted. 
4. Have confirmed or suspected CABP caused by a pathogen known to be resistant to any of 
the study drugs (e.g., MRSA, Pseudomonas aeruginosa, any pathogen of the 
Enterobacteriaceae Family) or attributable to etiologies other than community-acquired 

Nabriva Therapeutics AG 
Clinical Protocol NAB-BC-3781-3102 
 
 
V3.0:  17-Mar-2016 
Page 14 of 102 
Confidential Information 
bacterial pathogens (e.g., ventilator-associated pneumonia, hospital-acquired bacterial 
pneumonia, bacterial aspiration pneumonia, Pneumocystis jiroveci pneumonia or other 
fungal pneumonia, viral or mycobacterial infection of the lung). 
5. Have a noninfectious cause of pulmonary infiltrates (e.g., pulmonary embolism, chemical 
pneumonitis from aspiration, hypersensitivity pneumonia, congestive heart failure, 
bronchial obstruction, lung cancer, cystic fibrosis). 
6. Have confirmed or suspected pleural empyema (does not include sterile parapneumonic 
effusions). 
7. Have or be at risk for major cardiac events or dysfunction including, but not limited to, 
the following: 
• Known prolonged QT interval or family history of long QT syndrome 
• Clinically significant hypokalemia which has not been treated prior to randomization 
• Clinically unstable cardiac disease, including: unstable atrial fibrillation, symptomatic 
bradycardia, unstable congestive heart failure, active myocardial ischemia, or 
indwelling pacemaker 
• Complete left bundle branch block 
• Receipt within 7 days before enrollment of Class IA or Class III anti-arrhythmic 
medication or, in the opinion of the Investigator, subject may require such medication 
during the study. (Class 1A: Quinidine, Procainamide, Disopyramide; Class III: 
Amiodarone, Dofetilide, Ibutilide, Sotalol) 
• Receipt within 7 days before enrollment of medication that has the potential of 
prolonging the QT interval or, in the opinion of the Investigator, subject may require 
such medication during the study (see Appendix 5). 
8. Be receiving a strong p-glycoprotein inhibitor or a strong CYP3A inducer or inhibitor 
(see Appendix 4). 
9. Have a history of tendon disease/disorder, myasthenia gravis, or known or suspected 
central nervous system (CNS) disorders (severe cerebrovascular arteriosclerosis, 
epilepsy, or other risk factors that may predispose to seizures).   
10. Have a history of any hypersensitivity or allergic reaction to any fluoroquinolone, or any 
drug in the pleuromutilin class (i.e., retapamulin). 
11. Have severely impaired renal function, defined as estimated creatinine clearance (CrCl) 
≤ 30 mL/min as calculated by the Cockcroft-Gault formula. 
12. Have evidence of significant hepatic, hematologic, or immunologic disease including any 
of the following:  
• Known acute hepatitis, including acute viral hepatitis. 
• Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) level > 5 times 
the upper limit of normal (ULN),  
• Total bilirubin > 3 times the ULN (unless known Gilbert’s disease). 

Nabriva Therapeutics AG 
Clinical Protocol NAB-BC-3781-3102 
 
 
V3.0:  17-Mar-2016 
Page 15 of 102 
Confidential Information 
• Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) level > 3 times 
the upper limit of normal (ULN) and total bilirubin > 2 times the ULN. 
• History of cirrhosis of the liver. 
• Manifestation of end-stage liver disease, such as ascites or hepatic encephalopathy. 
• Current or anticipated neutropenia (< 500 neutrophils/mm3). 
• Thrombocytopenia (< 50 000 platelets/mm3). 
• Known infection with human immunodeficiency virus and a CD4 count < 200/mm3. 
13. Have known severe immunosuppression, including but not limited to receipt of 
corticosteroid therapy (≥20 mg of prednisone/day or equivalent for >4 weeks) within the 
previous 8 weeks; solid organ or bone marrow transplantation within the previous 12 
months; or currently receiving cytotoxic chemotherapy. 
14. Have a life expectancy of ≤ 3 months because of any disease other than the current 
episode of CABP (e.g., current or impending respiratory failure, acute heart failure, 
shock, acute coronary syndrome, unstable arrhythmia, hypertensive emergency, clinically 
relevant gastrointestinal bleeding, profound metabolic abnormality, or acute 
cerebrovascular event). 
15. Have participated in any study involving administration of an investigational agent or 
device within 30 days or ≤ 5 terminal elimination half-lives of the previous 
investigational medicinal product, whichever is longer, before enrollment. 
16. Have been previously treated with lefamulin or previously enrolled in this study. 
17. Have any condition that, in the opinion of the Investigator, would compromise the safety 
of the subject or the quality of the data. 
Duration of Study:  Each subject will participate for approximately 4-5 weeks. 
Drug Products:  Drug products will be supplied as follows: 
Drug Product 
Route 
Dosage Form/Strength 
Lefamulin 
PO 
600 mg of lefamulin as a yellow oval film coated immediate-release tablet 
Moxifloxacin 
PO 
400 mg of moxifloxacin as an over-encapsulated film-coated tablet 
 
Study Drug Assignment:  Subjects will be randomized in a 1:1 ratio to either lefamulin or 
moxifloxacin. 
Study Drug Administration:  The duration of blinded study drug administration will be 
7 days.  Subjects randomized to lefamulin will receive oral lefamulin 600 mg q12h for 5 days 
(10 doses) and oral moxifloxacin placebo q24h for 7 days (7 doses).  Subjects randomized to 
moxifloxacin will receive oral moxifloxacin 400 mg q24h for 7 days (7 doses) and oral 
lefamulin placebo q12h for 5 days (10 doses).   
On Day 1, study personnel will administer the first dose of study drug at the study site to all 
subjects as soon as possible after the diagnosis of CABP and completion of all required 

Nabriva Therapeutics AG 
Clinical Protocol NAB-BC-3781-3102 
 
 
V3.0:  17-Mar-2016 
Page 16 of 102 
Confidential Information 
Day 1 procedures as outlined in Table 1.  While subjects are hospitalized, all doses of study 
drug will be administered by hospital staff or study personnel.   
For Outpatients, or in the event a subject is discharged from the hospital during the study 
drug administration period, an adequate supply of study drug will be dispensed for self-
administration at home.  Subjects will be provided instructions regarding the dosing 
schedule.  Subjects may self-administer oral study drug at home with the following 
exception:  Study personnel will advise subjects who are Outpatients that they must return to 
the study site to assess CABP signs and symptoms at 96 ± 24 hours after the first dose of 
study drug.  Study personnel will inform Outpatients as to the timing of this required study 
site visit.  Subjects will be advised not to take their first dose of study drug at home that day, 
rather to bring their blister packs (used and unused) to the study site, where they will take 
their dose while supervised so that specific assessments can be performed both prior to and 
after taking the dose (i.e., ECGs and PK). 
On Study Day 1, if q12h dosing is not feasible, the 1st and 2nd doses may be administered as 
close as 8 hours apart, in order to allow 2 doses to be given on Day 1.  In this circumstance, 
the subject’s dosing schedule should be adjusted on Day 2 to a regular q12h morning and 
evening schedule.  Subsequently, every effort should be made to maintain a q12h dosing 
schedule.  When this is not possible, it is acceptable to administer doses within 4 hours of the 
scheduled dosing time (i.e., a minimum of 8 hours between doses). 
Study drug should be administered at least 1 hour before a meal or 2 hours after a meal.  
However, in the event that a subject has taken any of the following − antacids containing 
aluminum, products containing iron, or multivitamins containing zinc − study drug should be 
administered 2 hours before or 4 hours after consuming any of these medications.  Doses 
should be administered with approximately 240 mL (8 ounces) of water.  
Blinding:  Study drug will be blinded using a double-dummy technique.   
A member(s) of the Sponsor’s Clinical Pharmacology group (or designee) will be unblinded 
to treatment assignment, as appropriate, in order to perform PK/PD assessments.  A Data 
Monitoring Committee (DMC) will review study data by treatment group in accordance with 
the DMC Charter.  In addition, as needed to meet regulatory reporting requirements on a 
country-by-country basis, designated pharmacovigilance personnel may be unblinded to 
treatment status of individual subjects.  In this circumstance, and if there are no other 
concerns, neither the Sponsor nor the study personnel will be unblinded to treatment status. 
Study Design:  This multicenter, multinational, randomized, double-blind, double-dummy, 
active-controlled efficacy and safety study in subjects with CABP will be conducted at 
approximately 160 centers.  The planned enrollment is 738 subjects (369 subjects in the 
lefamulin group and 369 subjects in the moxifloxacin group) with PORT Risk Class II, III, or 
IV.  Eligible subjects will be randomized 1:1 to lefamulin or moxifloxacin, using an 
interactive response technology (IRT).  Subject randomization will be stratified according to 
PORT Risk Class (Risk Class II vs. III/IV), geographic region (US vs. ex-US), and prior 
(single dose) short-acting antibiotic therapy for CABP vs. none.   

Nabriva Therapeutics AG 
Clinical Protocol NAB-BC-3781-3102 
 
 
V3.0:  17-Mar-2016 
Page 17 of 102 
Confidential Information 
Subjects will be consented for the study prior to study assessments being performed and 
confirmation of eligibility.  Screening assessments will be performed within 24 hours before 
first dose of study drug.   
Subjects will be assessed for response at the following time points during the study: 
• Early Clinical Assessment (ECA):  96 ± 24 hours after the first dose of study drug. 
• End of Treatment (EOT):  within 2 days after the last dose of study drug (NOTE: every 
attempt should be made to conduct the EOT visit within 1 day after the last dose of study 
drug.  However, if this is not logistically feasible [e.g., visit would need to be conducted 
over a weekend], then conducting the visit within 2 days is acceptable.). 
• Test of Cure (TOC):  5-10 days after the last dose of study drug. 
• Late Follow Up (LFU):  Day 30 (± 3 days). 
 
An overview of the study design is provided in Figure 1 below. 
Figure 1. 
Study Design Overview 
 
 
Assessment of the 4 cardinal symptoms of CABP (dyspnea, cough, purulent sputum 
production, and chest pain) will be conducted daily; an assessment at 96 ± 24 hours after the 
first dose of study drug will determine Early Clinical Response (ECR) (as defined in the 
Primary Objective - FDA).  NOTE:  ECR will be determined programmatically based upon 
the Investigator’s assessment of the 4 cardinal symptoms of CABP; the decision to maintain 
the subject on study drug therapy will be made by the Investigator, based on all available 
data and his or her best clinical judgment. In addition, the Investigator’s Assessment of 
Clinical Response (IACR) will be performed at the EOT, TOC and LFU visits (Success, 
Failure and Indeterminate at EOT and TOC; Sustained Success, Relapse and Indeterminate at 
LFU).   

Nabriva Therapeutics AG 
Clinical Protocol NAB-BC-3781-3102 
 
 
V3.0:  17-Mar-2016 
Page 18 of 102 
Confidential Information 
Microbiological assessments will be performed at Screening, and then subsequently 
throughout the study as clinically indicated.  Samples will be taken for Gram’s staining, for 
diagnostic tests (serology, urine antigen tests, molecular tests), and for culture and 
antimicrobial susceptibility testing.  Subjects who have confirmed S. aureus bacteremia must 
be withdrawn from the study. 
Safety will be assessed by monitoring vital signs, ECG measurements, safety laboratory 
parameters, and recording of adverse events (AEs).  A Data Monitoring Committee (DMC) 
will review the safety data throughout the study.  
Blood samples for PK analyses will be collected from all subjects.  
Exploratory evaluation of a variety of health utilization variables (e.g., length of hospital 
stay, duration of antibiotic therapy, discharge status, discharge destination) as well as a PRO 
instrument (SF-12) will be administered.  The schedule of study procedures is provided 
immediately following the synopsis (Table 1:  Schedule of Assessments and Procedures). 
Statistical Considerations: 
Sample Size:  Utilizing an anticipated ECR responder rate of 79% in the ITT Analysis Set, 
1:1 randomization ratio (lefamulin:moxifloxacin) and a two-sided alpha of 0.025, a sample 
size of 738 subjects (369 subjects in the lefamulin group and 369 in the moxifloxacin group) 
provides 90% power to establish the non-inferiority (NI) of lefamulin to moxifloxacin for 
ECR using a NI margin of 10.0 % at the ECA.  Assuming an IACR success rate of 80% and 
85% in the mITT and CE-TOC Analysis Sets, respectively, and a clinical evaluability rate of 
80%, there is 91% power for demonstration of NI for IACR at the TOC Visit using a 10% NI 
margin. 
Treatment Comparison of Interest:  All comparisons will be for lefamulin vs. comparator 
therapy (moxifloxacin). 
Analysis Populations: 
• Intent-to-treat (ITT) Analysis Set:  All randomized subjects regardless of whether or not 
the subject received study drug. A subject is considered randomized when an IRT-
generated randomization number has been assigned. 
• Modified ITT (mITT) Analysis Set: All randomized subjects who receive any amount of 
study drug. Subjects are analyzed based on the randomized (i.e., assigned) treatment 
group. 
• Microbiological ITT (microITT) Analysis Set:  All subjects in the ITT Analysis Set who 
have at least 1 baseline “typical” bacterial pathogen known to cause CABP, Legionella 
pneumophila from an appropriate microbiological specimen, or who have CABP caused 
by Mycoplasma pneumoniae or Chlamydophila pneumoniae.  
• Clinically Evaluable (CE) Analysis Sets (CE-EOT, CE-TOC, and CE-LFU):  A subset of 
the ITT Analysis Set that will include subjects who meet the criteria for CABP described 
in Inclusion criteria Nos. 3 - 7, and who received at least the pre-specified minimal 
amount of the intended dose of study drug and duration of treatment, do not have an 

Nabriva Therapeutics AG 
Clinical Protocol NAB-BC-3781-3102 
 
 
V3.0:  17-Mar-2016 
Page 19 of 102 
Confidential Information 
indeterminate response based on the IACR (at EOT for the CE-EOT Analysis Set,  at 
TOC for the CE-TOC Analysis Set. and at LFU for the CE-LFU Analysis Set), did not 
receive concomitant antibacterial therapy that is potentially effective against CABP 
pathogens (except in the case of clinical failure) from the first dose of study drug through 
the EOT Visit (CE-EOT Analysis Set),  through the TOC Visit (CE-TOC Analysis Set) 
and through the LFU Visit (CE-LFU Analysis Set), and for whom there are no other 
confounding factors that interfere with the assessment of the outcome.  
• Microbiologically Evaluable (ME) Analysis Sets (ME-EOT, ME-TOC, and ME-LFU):  
Subjects who meet the criteria for both the microITT and the CE-EOT (ME-EOT) 
Analysis Sets, the CE-TOC (ME-TOC) Analysis Set or CE-LFU (ME-LFU) Analysis 
Set.  
• Safety Analysis Set:  All randomized subjects who receive any amount of study drug. 
Subjects are analyzed based on the study drug actually received. All safety analyses will 
be conducted in this population. 
• Pharmacokinetic Analysis Set:  All subjects who receive any amount of study drug will 
be included in the formal analysis of PK parameters providing they have at least 1 
evaluable PK sample. 
Variables for Analysis 
Primary Efficacy Analysis Variable 
• Proportion of Responders for ECR at 96 ± 24 hours following the first dose of study drug 
in the ITT Analysis Set (FDA)  
- 
Subjects will be programmatically defined as a Responder if the following 4 criteria 
are met: 
◦ 
Alive 
◦ 
Improvement in at least 2 of the 4 cardinal symptoms of CABP (see Section 6.11) 
the subject presented with at Baseline.  Improvement is defined as a decrease by 
at least 1 level of severity. 
◦ 
No worsening of any of the 4 cardinal symptoms of CABP. Worsening is defined 
as an increase from Baseline by at least 1 level of severity of any symptom. 
◦ 
Did not receive a concomitant antibiotic for the treatment of CABP.  
- 
Subjects will be programmatically defined as a Non-Responder if any of the 
following criteria are met: 
◦ 
Did not show an improvement in at least 2 of the 4 cardinal symptoms of CABP 
the subject presented with at Baseline.  Improvement is defined as a decrease by 
at least 1 level in severity; or 
◦ 
Worsening of any of the 4 cardinal symptoms of CABP. Worsening is defined as 
an increase from Baseline by at least 1 level in severity for any symptom; or 
◦ 
Received a concomitant antibiotic for the treatment of CABP; or 
◦ 
Died from any cause. 

Nabriva Therapeutics AG 
Clinical Protocol NAB-BC-3781-3102 
 
 
V3.0:  17-Mar-2016 
Page 20 of 102 
Confidential Information 
- Subjects will be programmatically defined as Indeterminate if the following 
criterion is met: 
◦ 
The symptom data are missing such that a response or non-response cannot be 
determined. 
• Proportion of subjects with an IACR of Success at TOC in the mITT and CE-TOC 
Analysis Sets (IACR definitions are provided below) (Primary for EMA and secondary 
for FDA) 
- 
Success:  The subject’s clinical signs and symptoms have resolved or improved such 
that no additional antibacterial therapy is administered for the treatment of the current 
episode of CABP. 
- 
Failure:  A subject is a treatment failure if any of the following is met:  
◦ 
Signs and symptoms of CABP have not resolved, not improved, or have worsened 
such that non-study antibacterial therapy is administered for the treatment of the 
current episode of CABP. 
◦ 
Measures of inflammation such as temperature or elevated WBC have worsened 
or failed to improve such that non-study antibacterial therapy is administered for 
treatment of the current episode of CABP. 
◦ 
Bacteremia has worsened or failed to improve resulting in administration of non-
study antibacterial therapy. 
◦ 
The occurrence of an AE requiring discontinuation of study drug and institution 
of non-study antibacterial therapy for the treatment of the current episode of 
CABP. 
◦ 
Death from any cause. 
- 
Indeterminate: Insufficient information is available to determine Success or Failure, 
specifically lost to follow-up. 
Secondary Efficacy Analysis Variables 
Efficacy will be assessed by ECR, IACR and by Microbiological Response.  
Microbiological Assessment 
The By-Pathogen Microbiological Response will be assessed using the categories for 
outcome in the microITT and ME analysis sets as follows: 
• Success includes: 
− Eradication:  the baseline causative pathogen was absent from repeat culture(s). 
− Presumed Eradication:  the IACR was Success, and culture was not repeated.  
• Failure includes: 
− Persistence:  the baseline causative pathogen was isolated in repeat culture(s).  
− Presumed Persistence:  the IACR was Failure and a culture was not repeated. 

Nabriva Therapeutics AG 
Clinical Protocol NAB-BC-3781-3102 
 
 
V3.0:  17-Mar-2016 
Page 21 of 102 
Confidential Information 
• Indeterminate:  
− The IACR was Indeterminate and a culture was not repeated. 
Safety Analysis Variables 
Safety will be assessed by monitoring vital signs, ECG measurements, clinical laboratory 
parameters, and AEs. 
Pharmacokinetic Analysis Variables 
Population PK modeling will be performed to determine the model-predicted plasma 
concentration time curves of lefamulin for each subject.  Calculated PK parameters will 
enable descriptive statistical analysis of PK variables such as the maximum observed drug 
concentration (Cmax) and area under the concentration-time curve (AUC) for lefamulin.   
Individual AUC values from Day 1 [all subjects] and Day 4 [Inpatients] or 96  ±  24 hours 
post first dose [Outpatients] (collected pre-dose, 1-2 h post dose and 3-4 h post dose, and a 8-
9 h post dose (the 8-9 h sample is required for inpatients and optional for outpatients) will be 
used for the PK/PD analysis.  The PK analysis based on population PK as well as a PK/PD 
analysis will be reported separately. 
Other Variables 
Exploratory evaluation of a variety of health utilization variables (e.g., length of hospital 
stay, duration of antibiotic therapy, discharge status, discharge destination) as well as a PRO 
instrument will be performed. 
Statistical Methods: 
A 2-sided unstratified 95 % confidence interval (CI) for the observed difference between 
treatment groups (lefamulin minus moxifloxacin) in ECR responder rates at 96 ± 24 hours 
post first dose will be calculated using a continuity corrected Z-statistic.  Non-inferiority for 
the primary efficacy analysis variable (FDA) will be concluded if the lower limit of the 
2-sided 95% CI is greater than –10.0% in the ITT Analysis Set. 
For the efficacy outcome measure of IACR of Success at TOC in the mITT and CE-TOC 
Analysis Sets, unstratified 95% CIs will be calculated using a continuity corrected Z-statistic 
(FDA secondary efficacy outcome).  For the primary analysis for the EMA, a stratified (for 
the randomization stratification factors) 2-sided 95% CIs will be calculated using the method 
of Miettinen and Nurminen.  Non-inferiority for the primary efficacy analysis variable 
(EMA) will be concluded if the lower limit of the 2-sided stratified 95% CI is greater than -
10% for both the mITT and CE-TOC Analysis Sets. 
The number and percentage of subjects with an ECR of Responder at 96 ± 24 hours will also 
be presented for the microITT Analysis Set, and a 2-sided unstratified 95% CI for the 
difference in responder rate will be calculated using a continuity-corrected Z-statistic.  
However, the formal test of NI will be conducted in the weighted (based on the inverse 
variance of each effect size) pooled population from this study and a second study in CABP. 

Nabriva Therapeutics AG 
Clinical Protocol NAB-BC-3781-3102 
 
 
V3.0:  17-Mar-2016 
Page 22 of 102 
Confidential Information 
The incidence of treatment-emergent AEs (TEAEs), serious AEs (SAEs), deaths, and 
discontinuations of study drug due to an AE or SAE will be summarized by System Organ 
Class (SOC) and Preferred Term according to the Medical Dictionary for Regulatory 
Activities (MedDRA), by relationship to study drug, and by severity.  The incidence of 
potentially clinically significant laboratory results, vital signs, and ECGs will be summarized. 

Nabriva Therapeutics AG 
 
Clinical Protocol NAB-BC-3781-3102 
 
 
V3.0:  17-Mar-2016 
Page 23 of 102 
Confidential Information 
Table 1. 
Schedule of Assessments and Procedures 
Assessment or Procedure 
Screening/ 
Baseline a 
Study Drug Administration 
    EOT d 
Visit 
Follow-up Visits 
Day 1b 
Day 2 
Day 3 
Days 4 to 7 c 
TOC e 
LFU f 
Informed consent form completed g 
X 
 
 
 
 
 
 
 
Verify inclusion/exclusion criteria 
X 
 
 
 
 
 
 
 
Medical and surgical history 
X 
 
 
 
 
 
 
 
Determine PORT Risk Class 
X 
 
 
 
 
 
 
 
Height and weight 
X 
 
 
 
 
 
 
 
Randomization 
X 
 
 
 
 
 
 
Prior and concomitant medications 
X 
X 
X 
X 
Daily 
X 
X 
X 
Vital signs including oxygen saturation and supplemental oxygen i 
X 
X 
X 
X 
Daily 
X 
X 
 
CABP signs and symptoms j 
X 
X 
X 
X 
Daily j 
X 
X 
X 
AEs and SAEs k 
X 
X 
X 
X 
Daily 
X 
X 
X 
12-lead ECG l 
X 
X 
 
 
Day 4 m 
 
 
 
Physical examination n 
X 
 
 
 
Day 4 o 
X 
X 
 
Hematology, clinical chemistry, urinalysis, procalcitonin (Central Lab) p 
X h 
 
 
Day 4 q 
X 
X 
 
Urine and serum pregnancy tests r 
X 
X 
 
 
 
 
 
 
CXR or CT scan 
X 
 
 
 
 
 
 
 
Arterial blood gases (PaO2, PaCO2) and pH [optional; record data if available] 
if clinically indicated 
Calculate CrCl (Cockcroft-Gault formula) 
X 
if clinically indicated 
Urine sample for L. pneumophila and S. pneumoniae antigen tests 
X h 
 
 
 
 
 
 
Blood sample for serologic tests for M. pneumoniae, C. pneumoniae, and L. pneumophila s 
X h 
 
 
 
 
 
X 
Blood sample for culture t 
X h 
if clinically indicated 
Respiratory sample for Gram’s stain and culture u 
X h 
if clinically indicated 
Pleural fluid and/or bronchoalveolar lavage (BAL) sample for Gram’s stain and culture v 
if clinically indicated 
Oropharyngeal and nasopharyngeal samples w 
X h 
 
 
 
 
 
 
Administer SF-12 health status questionnaire  
X h 
 
 
 
 
X 
 
Study drug administration x 
 
X 
X 
X 
Daily 
 
 
 
Blood samples for PK analyses 
 
Day 1y 
 
 
Day 4 y 
 
 
 
Investigator’s Assessment of Clinical Response (IACR) z 
 
 
 
 
 
X 
X 
X 
NOTE:  Hospitalization is not a requirement for this study.  However, all subjects, including Outpatients, must be evaluated at the investigational site by study personnel at the following 
time points/visits:  Screening/Baseline; Day 1; Day 4 / 96 ± 24 hours after the first dose of study drug; EOT; TOC; and LFU. 

Nabriva Therapeutics AG 
 
Clinical Protocol NAB-BC-3781-3102 
 
 
V3.0:  17-Mar-2016 
Page 24 of 102 
Confidential Information 
a: 
Perform Screening/Baseline assessments within 24 hours before the first dose of study drug.  Administration of study drug should begin as soon as possible after the diagnosis of 
CABP.  See Footnote x.  Assessments performed as part of routine standard of care prior to consent (e.g., chest X-ray, blood culture) may be used to satisfy study screening 
requirements; however, no study specific procedures may be performed prior to informed consent. 
b: 
Day 1 is the first day of study drug administration; subsequent study days are consecutive calendar days.  Assessments/ procedures on Day 1 should be performed prior to first dose. 
c: 
INPATIENTS will be assessed daily while hospitalized; thus, data required for ECR Assessment (96 ± 24 hours after the first dose of study drug) will be collected.  
 
OUTPATIENTS must have a visit at the study site that is 96 ± 24 hours after the first dose of study drug to assess CABP signs and symptoms for calculation of ECR.  Study 
personnel will inform subjects as to the timing of this visit during the course of daily telephone contact.  In addition to the assessment of CABP signs/symptoms, subjects will also have 
the following procedures/assessments performed at that study site visit:  ECGs, physical examination, AE monitoring, review of concomitant medications, vital signs, oxygen 
saturation, and blood sampling for PK analysis and safety laboratory evaluations.  Importantly, study personnel will advise OUTPATIENTS not to take their first dose of study drug at 
home that day, rather to bring their blister packs (used and unused) to the study site where they will take their dose while supervised; thus, specific assessments can be performed both 
prior to and after taking the dose (i.e., ECGs and PK).  See Footnotes i, k, l, m, o, p, and y below for details. 
d: 
Perform End of Treatment (EOT) assessments at the study site within 1 day (up to 2 days permitted) after the last dose of study drug or at the time of premature discontinuation of study 
drug or early withdrawal from study.  EOT assessments resulting from premature discontinuation of study drug should be done in place of the regular study visit on Days 1 to 7. 
e: 
Perform Test of Cure (TOC) assessments at the study site 5–10 days after the last dose of study drug.  All subjects will have a TOC Visit irrespective of early clinical failure or receipt 
of an alternative antibiotic.   
f: 
Perform Late Follow Up (LFU) assessments at the study site on Day 30 ± 3 days.  All subjects will have a LFU Visit irrespective of early clinical failure or receipt of an alternative 
antibiotic.   
g: 
Obtain informed consent before initiating any study-specific assessments or procedures. 
h: 
Assessment or procedure may occur at either Screening OR prior to the first dose of study drug on Day 1 once eligibility has been determined. 
i: 
All subjects will have vital signs and O2 saturation evaluated at Screening/Baseline and Day 1.  If screening/baseline and Day 1 occur on the same calendar day, vital signs and O2 
saturation do not need to be repeated. All subjects will also have assessments at EOT and TOC; at LFU, vital signs should be performed if medically indicated.  If EOT and the last day 
of study drug are the same day, vital signs do not need to be repeated, they may be recorded once on that day (i.e., as part of the EOT assessment).  Record the vital signs associated 
with the highest temperature after the first dose of study drug. 
 
INPATIENTS:  Vital signs, O2 saturation, and supplemental O2 usage will be measured daily.  If multiple vital signs are taken on a study day, the highest temperature and the vital signs 
associated with that high temperature will be recorded.   
OUTPATIENTS: In addition to the above time points, vital signs, O2 saturation and, if applicable, supplemental O2 usage will be measured at the study visit scheduled 96 ± 24 hours 
after the first dose of study drug.   
j: 
Study personnel will evaluate signs and symptoms of CABP at Baseline, daily while on study therapy, and at EOT, TOC, and LFU Visits. NOTE:  If Screening and Day 1 are the same 
day, signs and symptoms of CABP do not need to be repeated on Day 1.  If EOT and the last day of study drug are the same day, signs and symptoms of CABP should be done only 
once on that day (i.e., as part of the EOT assessment).  Signs and symptoms are not obtained at TOC or LFU if the subject was previously deemed to have an IACR of Failure. 
 
OUTPATIENTS:  Study personnel will contact subjects daily by telephone to track signs and symptoms of CABP; however, subjects must report to the study site for the 
assessment of CABP signs/symptoms 96 ± 24 hours after the first dose of study drug.  See Footnote c.   
k: 
Record AEs from the signing of the ICF through TOC and SAEs from signing of the ICF through LFU.  Study personnel will follow unresolved AEs and SAEs present at LFU until 
resolution or stabilization.  In addition, study personnel will monitor AEs for OUTPATIENTS in conjunction with daily telephone contacts for CABP signs/symptoms and at the study 
site visit 96 ± 24 hours after the first dose of study drug.  See Footnote c. 
l: 
At each required time point, ECGs should be recorded in triplicate within a 5-minute interval.  The subject should be stabilized in a supine position for 5 min before recording the 
ECG.  If Screening and Day 1 are on the same day, the Screening ECG can serve as the Day 1 ECG prior to the first dose of study drug; an additional ECG must be performed 1-3 hours 
after administration of first dose.  See Footnote m.   
m:  INPATIENTS:  The Day 4 ECG in triplicate is required prior to the first dose of study drug and again within 1-3 hours after the first dose of study drug. 
 
OUTPATIENTS:  The Day 4 ECG can be performed at the required study site visit 96 ± 24 hours after the first dose.  See Footnote c.  The Day 4 ECG in triplicate is required prior to 
the first dose of study drug and again within 1-3 hours after the first dose of study drug.   
n: 
A complete physical examination is performed at Baseline and directed physical examinations are performed thereafter.  

Nabriva Therapeutics AG 
 
Clinical Protocol NAB-BC-3781-3102 
 
 
V3.0:  17-Mar-2016 
Page 25 of 102 
Confidential Information 
o: 
INPATIENTS:  On Day 4, a directed physical examination will be performed.. 
OUTPATIENTS:  A directed physical examination will be performed at the study site visit scheduled 96 ± 24 hours after the first dose.  See Footnote c.    
p: 
Blood samples sent to the local laboratory for the purposes of determining study eligibility must be repeated and sent to the central laboratory following enrollment. Collect blood 
and/or urine at LFU only if subject had an abnormal (high/low flag) result at TOC.   
q: 
INPATIENTS:  On Day 4, blood and urine samples will be collected for safety laboratory evaluations. 
OUTPATIENTS: Blood and urine samples will be collected for safety laboratory evaluations at the study site visit scheduled 96 ± 24 hours after the first dose.  See Footnote c.   
r: 
A urine pregnancy test will be performed at the site on all females unless surgically sterile or at least 2 years post-menopausal.  A negative urine pregnancy test is required prior to 
randomization.  Serum must be collected on Day 1 prior to 1st dose and sent to the central lab for confirmatory testing. 
s: 
Blood to be collected and sent to central laboratory for serologic tests for M. pneumoniae, C. pneumoniae and L. pneumophila.   
t: 
Collect blood samples (2 sets via peripheral venipuncture) for microbiologic culture and susceptibility testing at the local/regional lab at Baseline and as clinically indicated during the 
study.  Repeat blood cultures after a positive result until sterilization is documented.  If possible, subjects who are discontinued from study drug due to confirmed MRSA or MSSA 
bacteremia should have blood samples collected for microbiologic culture prior to switching to alternate appropriate therapy.  All organisms isolated from blood cultures which are not 
considered contaminants will be sent to the central laboratory for confirmatory identification and susceptibility testing. 
u: 
All lower respiratory tract and expectorated sputum samples should be sent to the local/regional laboratory for Gram’s stain, culture and susceptibility testing.  A sputum sample will be 
taken at Screening for Gram’s staining, culture and susceptibility testing at the local/regional laboratory.  If a subject is unable to produce an adequate (> 25 polymorphonuclear [PMN] 
cells AND < 10 squamous epithelial cells per LPF) sputum sample at Screening, a specimen should be obtained, if possible, within 24 hours after the first dose of study drug. Gram’s 
stain and culture results from the local/regional laboratory will be recorded in the eCRF. Slides (stained and unstained) will also be sent to the central laboratory for a confirmatory 
reading of the Gram’s stain.  If possible, subjects who are discontinued from study drug due to clinical failure should have repeat cultures collected for microbiologic culture prior to 
switching to alternate appropriate therapy.  All organisms isolated from sputum samples, which are not considered contaminants, will be sent to the central laboratory for confirmatory 
identification and susceptibility testing.  In addition, a portion of all Baseline sputum samples must be frozen until sent to the central laboratory for quantitative PCR.  Subjects with a 
urinary antigen positive for Legionella spp. will also have a portion of their sputum sample sent frozen to the central laboratory for isolation of L. pneumophila. 
v: 
Collect pleural fluid samples and/or BAL only if medically indicated.  Gram’s stain samples, culture, and test the isolated pathogens for susceptibility.  Pathogens isolated from pleural 
fluid and/or BAL samples will be sent to the central laboratory for confirmatory identification and susceptibility testing.  If possible, pleural fluid samples should be incubated in blood 
culture bottles for optimal pathogen recovery. 
w: An oropharyngeal specimen (2 swabs) and a nasopharyngeal specimen (1 swab) will be collected and frozen until sent to the central laboratory.  The oropharyngeal specimen will be 
used for culture of M. pneumoniae and identification by PCR.  The nasopharyngeal specimen will be used for culture and identification by PCR of S. pneumoniae, and potentially, H. 
influenzae.   
x: 
Study personnel will administer the first dose of study drug at the study site, as soon as possible after the diagnosis of CABP and completion of all required pre-dose Day 1 procedures. 
On Day 1, if q12h dosing is not feasible, the 1st and 2nd doses may be administered as close as 8 hours apart, in order to allow 2 doses to be given on Day 1.  In this circumstance, the 
subject’s dosing schedule should be adjusted on Day 2 to a regular q12h morning and evening schedule.  Subsequently, every effort should be made to maintain a q12h dosing schedule.  
When this is not possible, it is acceptable to administer doses within 4 hours of the scheduled dosing time (i.e., a minimum of 8 hours between doses).  For Outpatients, or in the event a 
subject is discharged from the hospital during the study drug administration period, an adequate supply of study drug will be dispensed for self-administration at home.  Subjects will be 
provided instructions regarding the dosing schedule.  Subjects may self-administer oral study drug at home with the following exception:  Study personnel will advise subjects who are 
Outpatients that they must return to the study site to assess CABP signs and symptoms at 96 ± 24 hours after the first dose of study drug.  See Footnote c.  Administration of study drug 
may occur on the same calendar day as EOT, and if so will be completed before EOT assessments begin. 
y: 
Collect blood samples for PK analysis relative to the first dose of study drug.  Blood will be collected within 1 h pre-dose, 1-2 h post dose, and 3-4 h post dose, and 8-9 h post dose.  
INPATIENTS:  PK sampling should occur on Day 4 but, if not feasible, it can be done relative to the first dose on Day 5; the 8-9 h post dose is required.  OUTPATIENTS:  PK 
sampling will be done during the 96 ± 24 hours post 1st dose visit. The 8-9 h post dose sample is optional; however, it should be obtained if logistically feasible.   
z: 
Investigator to determine IACR - Success, Failure or Indeterminate (i.e., subject lost to follow up) at EOT and TOC and Sustained Success, Relapse or Indeterminate at LFU.  The 
Investigator will not determine Clinical Response at TOC or LFU if the subject was previously deemed to have an IACR of Failure. 

Nabriva Therapeutics AG 
Clinical Protocol NAB-BC-3781-3102 
 
 
V3.0:  17-Mar-2016 
Page 26 of 102 
Confidential Information 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS 
 
Abbreviation 
Definition 
24 h AUC/MIC 
24 h AUC over the MIC 
24 h AUCELF/MIC ratio 
AUC at site of infection over the MIC 
ABPI 
Association of British Pharmaceutical Industry 
ABSSSI 
Acute bacterial skin and skin structure infection 
ADME 
Absorption, Distribution, Metabolism, and Elimination 
AE 
Adverse event 
AGP 
α1-acid glycoprotein 
ALT 
Alanine aminotransferase 
AST 
Aspartate aminotransferase 
ATS 
American Thoracic Society 
AUC 
Area under the drug concentration–time curve 
BAL 
Bronchoalveolar Lavage 
BP 
Blood pressure 
C 
Celsius 
CABP 
Community-acquired bacterial pneumonia 
CA-MRSA 
Community-acquired MRSA 
CBC 
Complete blood count 
CDC 
Centers for Disease Control and Prevention 
CE 
Clinically Evaluable 
CE-EOT 
Clinically Evaluable at End-of-Treatment 
CE-LFU 
Clinically Evaluable at Late Follow Up 
CE-TOC 
Clinically Evaluable at Test-of-Cure 
CFR 
Code of Federal Regulation 
CFU 
Colony Forming Unit 
CI 
Confidence interval 
Cmax 
Maximum observed plasma concentration 
Cmin 
Minimum observed plasma concentration 
CNS 
Central Nervous System 
CrCl 
Creatinine clearance 
CS 
Clinically significant 
CT 
Computerized tomography 
CXR 
Chest x-ray 
CV [%] 
Coefficient of variation [%] 
CYP3A4 
Cytochrome P450 3A4 
DMC 
Data Monitoring Committee 
DSS 
Drug Safety Services 
ECA 
Early Clinical Assessment 

Nabriva Therapeutics AG 
Clinical Protocol NAB-BC-3781-3102 
 
 
V3.0:  17-Mar-2016 
Page 27 of 102 
Confidential Information 
Abbreviation 
Definition 
ECG 
Electrocardiogram 
ECR 
Early Clinical Response 
eCRF 
Electronic Case Report Form 
EDC 
Electronic Data Capture 
ELF 
Epithelial Lining Fluid 
EMA 
European Medicines Agency 
EOT 
End-of-Treatment 
ESBL 
Extended-spectrum β-lactamase  
EU 
European Union 
F 
Fahrenheit 
fAUC 
Area under the concentration-time curve of the unbound fraction of the 
drug 
FDA 
US Food and Drug Administration  
GCP 
Good Clinical Practice 
GI 
Gastrointestinal 
hERG 
Human ether a go go related Gene 
HIPAA 
Health Insurance Portability and Accountability Act 
HR 
Heart rate 
HSA 
Human serum albumin 
IAC 
Interim Analysis Committee 
IACR 
Investigator’s Assessment of Clinical Response 
IC50 
Half-maximal inhibitory concentration 
ICF 
Informed Consent 
ICH 
International Conference on Harmonization 
ICU 
Intensive Care Unit  
IDSA 
Infectious Diseases Society of America 
IEC 
Independent Ethics Committee 
INR 
International normalized ratio  
IRB 
Institutional Review Board 
IRT 
Interactive Response Technology 
ITT 
Intent-to-Treat 
IV 
Intravenous 
K3EDTA 
Tripotassium ethylene diamine tetraacetic acid 
LFU 
Late Follow-up 
LLQ 
Lower limit of quantification  
MAA 
Marketing Authorization Application 
LPF 
Low power field 
ME 
Microbiologically Evaluable 
MedDRA 
Medical Dictionary for Regulatory Activities 
ME-EOT 
Microbiologically Evaluable at End-of-Treatment 

Nabriva Therapeutics AG 
Clinical Protocol NAB-BC-3781-3102 
 
 
V3.0:  17-Mar-2016 
Page 28 of 102 
Confidential Information 
Abbreviation 
Definition 
ME-LFU 
Microbiologically Evaluable at Late Follow Up 
ME-TOC 
Microbiologically Evaluable at Test-of-Cure 
mg 
Milligram 
MIC 
Minimum inhibitory concentration  
MIC90 
Concentration of drug required to inhibit growth of 90% of pathogens 
microITT 
Microbiological Intent-to-Treat 
mITT 
Modified Intent-to-Treat 
mL 
Milliliter 
mm 
Millimeter 
mmHg 
Millimeter of mercury 
MRSA 
Methicillin-resistant Staphylococcus aureus 
ms 
Millisecond 
MSSA 
Methicillin-susceptible Staphylococcus aureus 
n 
Group size, number of replicates 
NaCl 
Sodium chloride 
NCS 
Not clinically significant 
NI 
Non-inferiority 
NOAEL 
No Observed Adverse Effect Level  
O2 
Oxygen 
Pa O2 
Partial Pressure of Arterial Oxygen 
PCR 
Polymerase Chain Reaction 
PCS 
Potentially clinically significant 
PD 
Pharmacodynamics 
p-gp 
p-glycoprotein 
Ph. Eur. 
European Pharmacopoeia 
PHL 
Potential Hy’s Law 
PK 
Pharmacokinetic 
PMN 
Polymorphonuclear 
PO 
By mouth (oral) 
PORT 
Pneumonia Outcomes Research Team 
PRO 
Patient-reported outcome 
PT 
Prothrombin time 
PTT 
Partial thromboplastin time  
PV 
Pharmacovigilance 
q12h 
Every 12 hours  
q24h 
Every 24 hours  
QA 
Quality Assurance 
QTc 
QT interval corrected for heart rate 
QTcF 
QT interval corrected according to Fridericia 
ΔQTcF 
QTcF change from baseline 

Nabriva Therapeutics AG 
Clinical Protocol NAB-BC-3781-3102 
 
 
V3.0:  17-Mar-2016 
Page 29 of 102 
Confidential Information 
Abbreviation 
Definition 
rRNA 
Ribosomal ribonucleic acid 
SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
SENTRY 
SENTRY Antimicrobial Surveillance Program 
SOC 
System organ class 
STD 
Sexually Transmitted Diseases  
SUSAR 
Suspected Unexpected Serious Adverse Event 
T> MIC 
Time plasma concentration exceeds the MIC 
t1/2 
Half-life 
TEAE 
Treatment-emergent adverse event 
TOC 
Test-of-Cure 
tRNA 
Transfer ribonucleic acid 
ULN 
Upper Limit of Normal 
US 
United States  
USP 
United States Pharmacopeia 
VRE 
Vancomycin-resistant enterococcus 
WBC 
White Blood Cell Count  
NOTE:  Table includes a comprehensive list of abbreviations used in lefamulin regulatory documents. 
 
 
 

Nabriva Therapeutics AG 
Clinical Protocol NAB-BC-3781-3102 
 
 
V3.0:  17-Mar-2016 
Page 30 of 102 
Confidential Information 
TABLE OF CONTENTS 
SPONSOR RELATED CONTACT DETAILS .........................................................................2 
PROTOCOL REVIEW AND APPROVAL FORM ..................................................................3 
INVESTIGATOR SIGNATURE PAGE ...................................................................................4 
AMENDMENT 2:  17-MAR-2016 ............................................................................................6 
AMENDMENT 1:  17-FEB-2016 .............................................................................................6 
SYNOPSIS ...............................................................................................................................11 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS ..........................................26 
TABLE OF CONTENTS .........................................................................................................30 
1 
INTRODUCTION ...........................................................................................................34 
1.1 
Background of the Disease and Treatment Options ..............................................34 
1.2 
Background on Lefamulin and the Pleuromutilins ................................................35 
1.3 
Mechanism of Action and Non-Clinical Pharmacology ........................................35 
1.4 
Nonclinical Pharmacokinetics and Safety .............................................................37 
1.5 
Summary of Clinical Data .....................................................................................39 
1.5.1 
Pharmacokinetics in Humans .......................................................................39 
1.5.2 
Efficacy ........................................................................................................41 
1.5.3 
Safety ...........................................................................................................41 
2 
STUDY OBJECTIVES ....................................................................................................42 
2.1 
Primary Objectives.................................................................................................42 
2.2 
Secondary Objectives.............................................................................................43 
2.3 
Additional Objectives ............................................................................................43 
3 
STUDY DESIGN.............................................................................................................43 
3.1 
Study Rationale ......................................................................................................45 
4 
STUDY POPULATION ..................................................................................................45 
4.1 
Inclusion Criteria ...................................................................................................45 
4.2 
Exclusion Criteria ..................................................................................................47 
5 
STUDY DRUG ADMINISTRATION ............................................................................49 
5.1 
Selection of Lefamulin Doses ................................................................................49 
5.2 
Selection of Comparator ........................................................................................50 
5.3 
Randomization .......................................................................................................51 
5.4 
Study Drug Treatment............................................................................................51 
5.5 
Blinding..................................................................................................................52 
5.6 
Unblinding of Therapy Assignments .....................................................................52 
5.7 
Adherence ..............................................................................................................53 
5.8 
Occupational Safety ...............................................................................................53 
6 
STUDY ASSESSMENTS AND PROCEDURES ...........................................................53 
6.1 
Inpatient and Outpatient Assessments ...................................................................54 

Nabriva Therapeutics AG 
Clinical Protocol NAB-BC-3781-3102 
 
 
V3.0:  17-Mar-2016 
Page 31 of 102 
Confidential Information 
6.1.1 
Outpatient Visit for ECR Assessment and Other Site Procedures ...............54 
6.2 
Medical/Surgical History and Physical Examination ............................................55 
6.3 
PORT Risk Class Assessment ...............................................................................55 
6.4 
Electrocardiograms ................................................................................................57 
6.5 
Vital Signs and Oxygen Saturation ........................................................................57 
6.6 
Chest X-Ray or CT Scan........................................................................................58 
6.7 
Arterial Blood Gases ..............................................................................................58 
6.8 
Prior and Concomitant Medications ......................................................................58 
6.8.1 
Prior Medications .........................................................................................58 
6.8.2 
Concomitant Medication ..............................................................................58 
6.9 
Prohibited Medications ..........................................................................................59 
6.10 
Nonpharmacologic Treatments and Procedures ....................................................60 
6.11 
Assessment of Clinical Signs and Symptoms of CABP ........................................60 
6.12 
Investigator’s Assessment of Clinical Response (IACR) ......................................62 
6.12.1 
Investigator’s Assessment of Clinical Response (IACR) at End of 
Treatment and Test of Cure .........................................................................62 
6.12.2 
Investigator’s Assessment of Clinical Response (IACR) at Late Follow 
Up .................................................................................................................62 
6.13 
Clinical Laboratory Tests (Safety) .........................................................................63 
6.14 
Sample Collection for Pharmacokinetic Analysis .................................................63 
6.14.1 
Sample Collection Methodology .................................................................64 
6.14.2 
Assay Methodology .....................................................................................64 
6.15 
Microbiological Assessment ..................................................................................65 
6.15.1 
Sputum Samples...........................................................................................65 
6.15.2 
Bronchoalveolar Lavage Samples (BAL) ....................................................65 
6.15.3 
Pleural Fluid Samples ..................................................................................66 
6.15.4 
Blood Cultures .............................................................................................66 
6.15.5 
Serological Testing ......................................................................................66 
6.15.6 
Urine Antigen Test .......................................................................................66 
6.15.7 
Oropharyngeal Specimen .............................................................................66 
6.15.8 
Nasopharyngeal Specimen ...........................................................................67 
6.16 
Health Utilization and Patient Reported Outcome.................................................67 
6.17 
Food and Beverage Restrictions ............................................................................67 
6.18 
Discontinuation from Treatment or Study .............................................................67 
6.18.1 
Discontinuation from Treatment ..................................................................67 
6.18.2 
Discontinuation from Study .........................................................................68 
6.18.3 
Individual Stopping Criteria ........................................................................68 
6.18.4 
Lost to Follow-up .........................................................................................69 
7 
ADVERSE EVENTS .......................................................................................................69 

Nabriva Therapeutics AG 
Clinical Protocol NAB-BC-3781-3102 
 
 
V3.0:  17-Mar-2016 
Page 32 of 102 
Confidential Information 
7.1 
Assessment of Severity (Intensity) ........................................................................70 
7.2 
Assessment of Relationship to Study Drug ...........................................................70 
7.3 
Serious Adverse Events .........................................................................................71 
7.4 
Symptoms of the Disease Under Study .................................................................73 
7.5 
Other Reportable Events ........................................................................................73 
8 
DRUG SUPPLIES ...........................................................................................................74 
8.1 
Lefamulin (BC-3781).............................................................................................74 
8.2 
Moxifloxacin ..........................................................................................................74 
8.3 
Placebo ...................................................................................................................74 
8.3.1 
Packaging and Labeling ...............................................................................74 
8.3.2 
Storage of Study Drugs ................................................................................74 
8.3.3 
Product Accountability ................................................................................74 
9 
STATISTICAL ANALYSIS ...........................................................................................75 
9.1 
Treatment Comparison of Interest .........................................................................75 
9.2 
Sample Size Determination....................................................................................75 
9.3 
Analysis Populations ..............................................................................................76 
9.3.1 
Intent-to-Treat Analysis Set (ITT) ...............................................................76 
9.3.2 
Modified Intent-to-Treat Analysis Set (mITT) ............................................77 
9.3.3 
Safety Analysis Set ......................................................................................77 
9.3.4 
Microbiological Intent-to-Treat Analysis Set (microITT) ...........................77 
9.3.5 
Clinically Evaluable Analysis Set ................................................................77 
9.3.6 
Microbiologically Evaluable Analysis Set ...................................................77 
9.3.7 
Pharmacokinetic Analysis Set......................................................................77 
9.4 
Criteria for Evaluation ...........................................................................................78 
9.4.1 
Primary Efficacy Analysis Variable ............................................................78 
9.4.2 
Secondary Efficacy Analysis Variables .......................................................78 
9.4.2.1 
Clinical Outcome ...............................................................................78 
9.4.2.2 
Microbiological Assessment ..............................................................78 
9.4.3 
Safety Analysis Variables ............................................................................79 
9.4.4 
Pharmacokinetic Analysis Variables ...........................................................79 
9.4.5 
Other Variables ............................................................................................79 
9.5 
Demographic and Baseline Characteristics ...........................................................80 
9.6 
Efficacy Analysis ...................................................................................................80 
9.6.1 
Primary Efficacy Analysis ...........................................................................81 
9.6.2 
Secondary Efficacy Analyses ......................................................................82 
9.6.3 
Additional Efficacy Analyses ......................................................................83 
9.7 
Safety Analysis ......................................................................................................83 
9.8 
Handling of Missing Data ......................................................................................84 
9.9 
Pharmacokinetic Analyses .....................................................................................84 

Nabriva Therapeutics AG 
Clinical Protocol NAB-BC-3781-3102 
 
 
V3.0:  17-Mar-2016 
Page 33 of 102 
Confidential Information 
9.10 
Health Utilization Variables and Patient Reported Outcome ................................85 
10 STUDY MONITORING .................................................................................................85 
10.1 
Clinical Monitoring ................................................................................................85 
10.2 
Independent Data Monitoring Committee (DMC) ................................................85 
11 IEC/IRB APPROVAL .....................................................................................................86 
12 ETHICAL CONDUCT OF THE STUDY .......................................................................86 
13 INFORMED CONSENT .................................................................................................86 
14 QUALITY ASSURANCE AND QUALITY CONTROL ...............................................87 
15 DATA HANDLING AND RECORD KEEPING ...........................................................87 
15.1 
Data Handling ........................................................................................................87 
15.2 
Subject Confidentiality ..........................................................................................88 
15.3 
Computer Systems .................................................................................................88 
15.4 
Data Entry ..............................................................................................................88 
15.5 
Data Validation ......................................................................................................89 
15.6 
Record Keeping .....................................................................................................89 
16 TERMINATION OF STUDY .........................................................................................89 
17 FINANCING AND INSURANCE ..................................................................................90 
18 PUBLICATION POLICY ...............................................................................................90 
19 LIST OF REFERENCES .................................................................................................92 
20 APPENDICES .................................................................................................................96 
 
 
 

Nabriva Therapeutics AG 
Clinical Protocol NAB-BC-3781-3102 
 
 
V3.0:  17-Mar-2016 
Page 34 of 102 
Confidential Information 
1 
INTRODUCTION 
1.1 Background of the Disease and Treatment Options  
Community-acquired bacterial pneumonia (CABP) is a commonly occurring serious 
infection that requires systemic antibiotic therapy and is associated with substantial 
morbidity, mortality, and considerable healthcare costs.  It is the leading cause of death from 
infectious diseases in the United States (US) and, when combined with influenza, remains the 
eighth leading cause of death in the US (CDC, 2013).  In Europe, there are 44 cases of CABP 
for every 1 000 patients treated in a single general practice (Lim et al., 2009), while in the 
US, 5.6 million cases of CABP lead to as many as 1.1 million hospitalizations and > 53 000 
deaths annually (CDC, 2013). 
Community-acquired bacterial pneumonia is more common in the elderly, with an incidence 
that is 2- to 4-times greater in those > 60 years of age than in those ≤ 50 years.  The mortality 
rate in the US and Europe is < 1 % for individuals with CABP that do not require 
hospitalization; however, the average mortality rate is 12 % to 14 % among those 
hospitalized (Fine et al., 1996; Fine et al., 1997; Lim et al, 2009).  Individuals who are 
admitted to the intensive care unit (ICU), who are bacteremic, or who are admitted from a 
nursing home, have a mean mortality rate of 30% to 40% (Mandell et al., 2007; Lim et al., 
2009). 
The most common organisms of CABP identified by culture include Streptococcus 
pneumoniae, Haemophilus influenzae, Staphylococcus aureus, Moraxella catarrhalis, and 
selected Gram-negative pathogens.  The incidence of CABP due to atypical pathogens — 
Mycoplasma pneumoniae, Chlamydophila pneumoniae, and Legionella pneumophila — lies 
between 20% and 28% depending on the region (Arnold et al., 2007). 
The emergence of pathogens resistant to antimicrobials has become an increasingly 
complicating factor in the selection of empiric therapy for CABP.  Antimicrobial 
susceptibility data for respiratory pathogens in the US reveal high rates of resistance among 
S. pneumoniae and H. influenzae.  A surveillance program conducted between 2008 and 2010 
in the US showed that, of 3 329 S. pneumoniae strains, 21.1 % were penicillin non-
susceptible or resistant.  Increases in an already elevated resistance rate for erythromycin 
(38.4% to 41.7%) were also observed in the same study (Pfaller et al., 2012).  Recent global 
surveillance studies have revealed increased resistance to fluoroquinolones in all monitored 
bacterial species with the exception of S. pneumoniae and H. influenzae (Dalhoff, 2012). 
M. pneumoniae is a common pathogen of respiratory tract infection in children and 
adolescents and can cause serious pneumonia and extra-pulmonary complications (Waites 
and Talkington, 2004).  Current preferred treatment is with a macrolide antibiotic.  In recent 
years, however, many countries have reported the isolation of clinically drug-resistant strains, 
the main mechanism of resistance being a mutation in the 23S ribosomal ribonucleic acid 
(rRNA) gene which is the target of macrolide antibiotic action.  These resistant isolates 
remain susceptible to fluoroquinolones or tetracyclines, but use of these antibiotics is limited 
in children (Liu et al., 2014). 

Nabriva Therapeutics AG 
Clinical Protocol NAB-BC-3781-3102 
 
 
V3.0:  17-Mar-2016 
Page 35 of 102 
Confidential Information 
S. aureus, including methicillin-resistant S. aureus (MRSA), has emerged as an important 
pathogen in CABP.  In a retrospective analysis that included hospitalized patients with 
microbiologically-confirmed CABP, approximately 25.5% of these patients were culture-
positive for S. aureus and, among these patients, 6.3% had MRSA isolated (Kollef et al., 
2005).  In general, the hospitalized patients with pneumonia due to S. aureus in this study 
had an increased mortality rate.  These findings correlate with recent case series of CABP 
due to community-acquired MRSA (CA-MRSA), which describe severe, necrotizing 
pneumonia in previously healthy young individuals (Francis et al, 2005; Hidron et al., 2009).  
Optimal management for these patients is not yet clear, and even the best available treatment 
may still result in poor outcomes (Gillet et al., 2007).  Therefore, there is a need for more 
treatment options for CABP caused by MRSA. 
1.2 Background on Lefamulin and the Pleuromutilins 
Lefamulin is a potent, semi-synthetic antibacterial belonging to a novel class known as the 
pleuromutilins.  The oral formulation of lefamulin is under investigation in this study.  The 
first marketed representative of the pleuromutilin class for human use is retapamulin 
(GlaxoSmithKline), approved in 2007 in the US (AltabaxP®) for the topical treatment of 
impetigo and in Europe (Altargo®) for the topical short-term treatment of impetigo and 
infected small lacerations, abrasions or sutured wounds.  Tiamulin (Denagard®) and 
valnemulin (Econor®), two other semi-synthetic pleuromutilin derivatives, have been used 
systemically in veterinary medicine for many years. 
1.3 Mechanism of Action and Non-Clinical Pharmacology 
Lefamulin is a prokaryotic protein synthesis inhibitor.  Its novel mode of action is mediated 
by a unique interaction with the central part of domain V of 23S rRNA, subsequently 
preventing the correct positioning of the CCA-ends of transfer ribonucleic acid (tRNA) for 
peptide transfer (Davidovich et al., 2007).  The uniqueness of this mechanism implies a very 
low probability of cross-resistance with other antibacterial classes. 
Lefamulin’s in vitro antibacterial profile covers the most important bacterial pathogens 
causing community acquired bacterial pneumonia (CABP) acute bacterial skin and skin 
structure infection (ABSSSI) and sexually transmitted diseases (STD).  The antibacterial 
spectrum comprises S. aureus including MRSA and CA-MRSA, ß-haemolytic streptococci 
including S. pyogenes and S. agalactiae, Enterococcus faecium including vancomycin-
resistant enterococci (VRE), S. pneumoniae, H. influenzae, M. catarrhalis, the atypical 
respiratory pathogens L. pneumophila, C. pneumoniae, and M. pneumoniae, and organisms 
causing STD such as Neisseria gonorrhoeae, Chlamydia trachomatis, 
Mycoplasma genitalium among others.  Moreover, lefamulin remains active against clinical 
isolates resistant to the following antimicrobial(s) (classes):  macrolides, lincosamides, 
streptogramin B, oxazolidinones, tetracyclines, ß-lactams, quinolones, trimethoprim-
sulfamethoxazole, mupirocin, and vancomycin as demonstrated in cross-resistance studies.  
The only exceptions are the rarely encountered Staphylococcus spp. producing the Cfr-
methyltransferase and the Vga(A)-efflux pump, where lefamulin showed reduced activity.  
Although some linezolid-resistant isolates have a minimum inhibitory concentration (MIC) 
of >1 µg/mL for lefamulin, no consistent cross-resistance could be observed with linezolid.  

Nabriva Therapeutics AG 
Clinical Protocol NAB-BC-3781-3102 
 
 
V3.0:  17-Mar-2016 
Page 36 of 102 
Confidential Information 
Multiple interaction sites with the ribosomal target are the most likely explanation for the 
observed low mutation frequency of below 10-11.  In vitro resistance development was a slow 
and stepwise process with resistant S. aureus clones being selected at sub-MIC levels only 
after 22-42 passages, whereas no stable resistant clones could be selected for S. pyogenes and 
S. pneumoniae. 
Susceptibility testing of lefamulin was performed with >13,600 contemporary clinical 
isolates including >7800 staphylococcal strains (including MRSA and methicillin-susceptible 
S. aureus [MSSA] strains) collected from patients world-wide, including the SENTRY 
Antimicrobial Surveillance Program (SENTRY) in 2010 (Paukner et al, 2013).  Lefamulin 
demonstrated in vitro antibacterial activity (MIC90) against the most relevant respiratory 
pathogens including S. pneumoniae (0.25 µg/mL), H. influenzae (2 µg/mL), M. catarrhalis 
(0.25 µg/mL), L. pneumophila (0.5 µg/mL), M. pneumoniae (0.006 µg/mL), and 
C. pneumoniae (0.04 µg/mL).  When compared with other antibiotics used to treat bacterial 
pneumonia such as macrolides, ß-lactams, fluoroquinolones or doxycycline, lefamulin was 
among the most active compounds in vitro irrespective of resistance phenotype present in 
S. pneumoniae or H. influenzae.  Furthermore, lefamulin showed complete activity (100% 
susceptibility) against S. pneumoniae that are resistant to macrolides (36.2-37.4%; SENTRY 
2010) or to levofloxacin (1.0-1.1%; SENTRY 2010) (Sader et al., 2012; Paukner et al., 
2013).  
Analysis of in vitro bacterial-killing properties suggested that lefamulin exhibits bactericidal 
activity against S. pneumoniae and H. influenzae, while it is predominantly a bacteriostatic 
agent against S. aureus.  In vivo, the extent of bacterial killing in neutropenic mice was 
excellent for most strains of S. pneumoniae and moderate for strains of S. aureus. 
The potential for synergy/antagonism of lefamulin with various currently marketed 
antibiotics was evaluated using the broth microdilution technique according to CLSI (M7-
A9, 2012) for S. aureus (n = 6), S. pneumoniae (n = 6), ß-hemolytic S. pyogenes (n = 3), 
S. agalactiae (n = 3), H. influenzae (n = 6), Enterobacteriaceae (n = 10) and P. aeruginosa 
(n = 2).  Lefamulin was largely indifferent/additive when combined with other antibacterial 
agents and did not exhibit an antagonistic effect with any antibiotic against any bacterial 
strains tested, including those with important resistance phenotypes (e.g., MRSA and ESBL).   
No apparent synergy was observed with the exception of a trend towards synergy observed 
against S. aureus isolates when lefamulin was combined with doxycycline (in 5 of 6 tested 
isolates) and for all S. pneumoniae isolates (6 of 6 tested isolates) when lefamulin was 
combined with aztreonam.  Based on studies completed to date, there is no potential concern 
if lefamulin is used in combination with other antibacterial agents.  
Lefamulin accumulated 30- to 50-fold in murine macrophages at clinically relevant 
concentrations of 1 and 5 µg/mL.  The antimicrobial potency of lefamulin was unaffected by 
lung surfactant. 
A number of animal infection models have established the in vivo efficacy of lefamulin, 
including the septicemia, thigh infection, and pneumonia models in mice.  Lefamulin has 
proven to be highly efficacious against S. aureus (MSSA and MRSA) and S. pneumoniae 
(penicillin-susceptible and penicillin-resistant S. pneumoniae).  Evaluation of the 

Nabriva Therapeutics AG 
Clinical Protocol NAB-BC-3781-3102 
 
 
V3.0:  17-Mar-2016 
Page 37 of 102 
Confidential Information 
pharmacokinetic/pharmacodynamic (PK/PD) target associated with efficacy was performed 
using a neutropenic murine thigh and lung infection model.  The major parameters driving 
efficacy for both S. aureus and S. pneumoniae were the 24 h area under the drug 
concentration–time curve (AUC) over the MIC (24 h AUC/MIC) followed by the duration of 
time plasma concentrations exceeded the MIC (T > MIC).  The activity of the drug was only 
minimally diminished in immunocompromised mice in comparison to immuno-competent 
mice.  In lung infections caused by S. pneumoniae or S. aureus, lefamulin showed enhanced 
activity when compared to the outcome in the murine thigh infection model.  Investigations 
of the exposure levels in the epithelial lining fluid (ELF) in mice were consistent with the 
observed good efficacy against lung infections.  For the PK/PD analyses, the plasma 24 h 
fAUC/MIC ratio, as well as the AUC at site of infection over the MIC (24 h AUCELF/MIC 
ratio), were evaluated on the basis of murine lung infections caused by S. pneumoniae and S. 
aureus.  
1.4 Nonclinical Pharmacokinetics and Safety 
Pharmacokinetic studies after oral and IV administration demonstrated a dose proportional 
systemic exposure of lefamulin in all species tested.  Moderate to high plasma protein 
binding of 73 % to 88 % in humans and 61 % to 81 % in animals was observed.  However, 
lefamulin displayed low binding affinity to the 2 major drug binding human plasma proteins 
(human serum albumin [HSA] and α1-acid glycoprotein [AGP]) and, despite the observed 
moderate to high protein binding, its in vitro antimicrobial activity was maintained in the 
presence of serum.  This is suggestive of a weak and loose association of the drug with 
plasma proteins and probably explains the rapid tissue distribution observed across the 
species, including humans.  Quantitative whole body autoradiography in rats after IV bolus 
administration showed rapid distribution into tissues and organs consistent with the apparent 
low protein binding affinity observed in vitro.  The concentrations measured in the majority 
of the tissues including skin and soft tissues and lungs were higher compared to the amounts 
measured in blood.  
In vitro metabolic stability testing of lefamulin predicted a mild to moderate influence of 
Phase I reactions by CYP450 enzymes on its overall metabolism, while Phase II metabolism 
will have only a very limited effect.  Using isolated recombinant CYP450 isoenzymes, 
CYP3A4 and 3A5 were identified as lefamulin metabolizing enzymes.  Lefamulin did not 
inhibit CYP1A, 2B6, 2C9, 2C19, 2D6, 2C8, or 2E1 to a clinically relevant extent.  Lefamulin 
was identified as a p-glycoprotein (p-gp) substrate and a p-gp inhibitor and was capable of 
saturating its own efflux in Caco-2 cells.  This observation is in-line with the observed dose-
dependent increase in bioavailability, as seen in the oral single ascending dose study in 
humans (NAB-BC-3781-1101).  Lefamulin did not induce CYP1A2 and CYP3A4 in human 
hepatocytes.  Consequently, it is not expected that lefamulin will induce CYP1A2 and 
CYP3A4 or p-gp in a clinical setting. 
All data obtained so far suggest that the non-renal route of excretion drives the clearance of 
lefamulin.  Fecal excretion in the bile (and/or via the gut mucosa) is likely the most important 
route of elimination for this compound, as confirmed by a mass balance study in rats, 
showing 96 % total recovery, mainly in feces (82 %) and urine (14 %).  Furthermore, all 

Nabriva Therapeutics AG 
Clinical Protocol NAB-BC-3781-3102 
 
 
V3.0:  17-Mar-2016 
Page 38 of 102 
Confidential Information 
intra-organ radioactivities approached the lower limit of quantification (LLQ) within 72 h, 
indicating a total elimination of the drug and/or its metabolites.  
The safety of lefamulin has been investigated in a number of safety pharmacology and 
toxicology studies conducted in vitro and in vivo in different rodent and non-rodent animal 
species.  Safety and toxicology studies have been performed to support oral and IV use in 
human.  Studies include acute and repeated dose toxicity, local tolerance and genotoxicity 
testing, development and reproductive toxicity, safety pharmacology, and PK/toxicokinetic 
profiling in rodent and non-rodent species.  No clear differences between male and female 
animals were seen in toxicity or absorption, distribution, metabolism, and elimination 
(ADME) studies.  
Lefamulin did not show any effects on the central and autonomic nervous system in rats or 
on the respiratory system in cynomolgus monkeys.  A potential for QT/QTc interval 
prolongation was noted after a single IV dose of 40 mg/kg.  In vitro IKr (hERG) assays and a 
study using rabbit Purkinje fibers showed a potential for QT/QTc prolongation, but did not 
demonstrate any pro-arrhythmic potential for lefamulin at clinically relevant concentrations. 
Four-week, IV, repeat-dose toxicity studies in rats and monkeys resulted in NOAELs of 75 
and 120 mg/kg daily dose, respectively, the highest doses tested.  The NOAEL in pivotal 4-
week oral repeat-dose toxicity studies in rats and cynomolgus monkeys was 300 and 
70 mg/kg daily dose, respectively.  In both species, the pivotal repeat-dose toxicity studies 
did not indicate any systemic target organ toxicity. 
Intravenous administration to rats resulted in local effects at the infusion site.  These 
reversible local effects are likely induced by inflammatory irritation caused by the indwelling 
catheter together with lefamulin.  The effect might have been more pronounced due to the 
small vessel size and the lower blood flow/volume in rats.  Intravenous administrations to 
monkeys up to and including 120 mg/kg/day did not show any signs of local intolerance. 
Oral administrations in monkeys up to and including 70 mg/kg/day were well tolerated by the 
gastrointestinal (GI) tract.  Doses of 200 mg/kg/day caused emetic periods and diarrhea 
associated with body weight loss and poor physical condition.  Gastrointestinal tract 
intolerability following oral dosing of 600 and 450 mg/kg/day was also described in rats.  
The dose of 70 mg/kg/day corresponds to 4 200 mg daily in 60 kg humans and exceeds the 
maximum intended daily dose of 1 200 mg.  Lefamulin did not evidence any genotoxic 
potential, as demonstrated by in vitro and in vivo mutagenicity and clastogenicity assays. 
No treatment-related changes were noted in female or male reproductive organs of rats or 
monkeys following 14 or 28 days repeated dosing.  Embryo-fetal development toxicity 
studies with lefamulin performed in rats and rabbits did not indicate a potential for 
teratogenicity and the corresponding NOAELs were set at the highest doses tested, 100 and 
60 mg/kg/day (IV), respectively.  Fertility studies performed in rats did not show any adverse 
effect on reproductive indices and the NOAEL was established at 75 mg/kg/day (IV), the 
highest dose tested in both genders.  

Nabriva Therapeutics AG 
Clinical Protocol NAB-BC-3781-3102 
 
 
V3.0:  17-Mar-2016 
Page 39 of 102 
Confidential Information 
BC-8041, the main human metabolite of lefamulin, did not demonstrate a potential for 
QT/QTc prolongation (hERG assay) or genotoxicity (Ames and mouse lymphoma assay), 
and exhibited no teratogenicity in a rat embryo-fetal development toxicity study. 
The safety and toxicology program provided sufficient and pertinent information on the 
safety profile of lefamulin and its main human metabolite, BC-8041, concluding that the drug 
candidate has no indices of toxicity in animals that would preclude its use in humans.  These 
studies are described in more detail in the Investigator’s Brochure. 
1.5 Summary of Clinical Data 
Lefamulin has been administered as single or multiple-doses orally and by IV infusions to 
healthy subjects in 17 completed Phase 1 studies and IV to subjects with ABSSSI in a 
completed Phase 2 study.  In these studies, lefamulin was found to be well tolerated at the 
doses that exceed those to be used in the current study (i.e., 600 mg per oral administration).  
In the 17 Phase 1 studies, 321 male and female healthy subjects were exposed to lefamulin, 
12 of whom were ≥ 65 years of age.  In the Phase 2 study, 141 subjects (95 male, 46 female) 
were exposed to lefamulin, 7 of whom were ≥ 65 years of age (4 in the 100 mg group, 3 in 
the 150 mg group) (Prince et al., 2010; Prince et al., 2013; Wicha et al., 2010; Zeitlinger et 
al., 2011).  
1.5.1 
Pharmacokinetics in Humans 
Tissue distribution studies in healthy volunteers showed rapid lefamulin distribution 
achieving therapeutic exposures in relevant target tissues for the treatment of both respiratory 
tract and skin infections following IV and PO administration.  Following a single 150 mg IV 
infusion, lefamulin showed higher exposure in epithelial lining fluid (ELF) as compared to 
the penetration into skin tissues (Zeitlinger et al., 2016).  This pattern of tissue distribution 
has also been observed in ELF of mice.  Therefore, the exposures in plasma and in ELF were 
used for the determination of the AUC/MIC ratio for target attainment analyses.  
The plasma concentration-time curve of intravenously administered lefamulin in humans 
showed a multi-phasic decline.  Following the end of infusion (i.e., the maximal 
concentration [Cmax]), there is a rapid distribution phase over 0.5 h followed by an extended 
elimination phase with a mean half-life (t1/2) of 8.6 h to 11.8 h.  The major elimination route 
for lefamulin was non-renal.  There were no statistically significant effects of age, 
demographics (body weight, height, or body mass index) or gender on the PK parameters of 
lefamulin.  In addition, no significant influence of the health status on the total body 
clearance or drug distribution of lefamulin was observed.  
Oral administered lefamulin is characterized by a plasma concentration time curve with a 
rapid absorption describing a bimodal peak, suggesting a mixed order absorption.  The initial 
peak plasma concentration occurs 20-60 minutes after administration, followed by a second 
peak observed between 1-4 hours after dosing. Following every 12 hour intravenous infusion 
or oral administration, steady-state is achieved after two days and thereafter, trough levels 
(Cmin) remain consistently linear throughout the duration of the treatment. After oral 

Nabriva Therapeutics AG 
Clinical Protocol NAB-BC-3781-3102 
 
 
V3.0:  17-Mar-2016 
Page 40 of 102 
Confidential Information 
administration of an immediate-release (IR) tablet containing 600 mg of lefamulin, exposure 
— as measured by AUC (the driver of efficacy) — was equivalent to a 150 mg IV dose, the 
higher of 2 doses evaluated in the Phase 2 study of lefamulin in the treatment of ABSSSI 
(NAB-BC-3781-2001) (Wicha et al., 2013).  
Lefamulin was best absorbed when taken on an empty stomach. A food-effect study 
involving administration of lefamulin to healthy female and male volunteers under fasting 
conditions and with a high-fat meal indicated an effect of food on the absorption process and 
bioavailability of lefamulin. The CI90 % for both Cmax and AUC were outside of the 
recommended acceptance range of 80 %-125 %. While the reduced Cmax is seen as not 
clinically relevant in terms of efficacy, the effect of the decreased AUC was evaluated using 
PK/PD analysis. Exposure response (PK/PD) analysis based on an oral popPK model, robust 
surveillance data, and pre-clinically derived free plasma AUC/MIC ratio targets against 
S. pneumoniae and S. aureus showed a high probability of success of ≥ 99.4 % regardless of 
food. However, in the simulation of lung exposures in ELF (AUCELF/MIC) using the 
modified popPK model overall probability dropped down to ≥ 85.6 % in the fed population 
on Day 1, with a morning and an evening dose after a high fat, high calorie meal. Although 
we believe that the probability analysis based on the simulated fed state data represent a 
worst case scenario for oral absorption and that the prediction of ELF exposures might be 
underestimated, to mitigate any risk associated with co-administration of oral lefamulin with 
food during the Phase 3 oral trial, we plan to recommend in the protocol that study drug be 
administered at least 1 hour before a meal or 2 hours after a meal.  
Overall, lefamulin metabolism is low.  In general, the PK profiles of the metabolites in 
plasma resemble the profiles of the parent drug, resulting in similar or shorter terminal t1/2 
values.  BC-8041 was the only metabolite that could be identified exceeding the limit of 
10 % of total drug related systemic exposure at steady-state when lefamulin was given orally.  
Therefore, accumulation of any metabolite is unlikely.  BC-8041 exposure at steady-state in 
humans at lefamulin therapeutic doses is covered by toxicology studies in the cynomolgus 
monkey.  In drug-interaction studies performed with lefamulin, no issues of clinical 
significance have been identified so far.  In drug-interaction studies with midazolam or 
ketoconazole, lefamulin can be classified as having only a weak interaction with CYP3A 
after IV administration.  Oral co-administration of ketoconazole and lefamulin resulted in a 
moderate interaction, likely as a result of a reduced first-pass effect in the gut wall.  Based on 
the current safety profile of lefamulin and its main metabolite, BC-8041, it is not expected 
that a drug-drug interaction with potent CYP3A and p-gp inhibitors will be of sufficient 
clinical significance to justify a dose adjustment.  
Most recently, a Phase 1 study (NAB-BC 3781-1107) evaluating the safety, absolute and 
relative bioavailability, and the potential effect of co-administration of food on the 
pharmacokinetics of lefamulin administered as a 600 mg immediate release tablet compared 
with the IV formulation and a capsule formulation containing lefamulin API was completed. 
This study demonstrates that the AUC of lefamulin achieved with the 600 mg IR tablet 
formulation in the fasted state is comparable with that observed following administration of a 
150 mg IV dose. A lower Cmax (901 ng/mL), AUC0-inf (6 630 ng·h/mL), and bioavailability 
(21.0% versus 25.8 %) were observed with the 600 mg IR tablet in the fed compared with the 
fasted state. 

Nabriva Therapeutics AG 
Clinical Protocol NAB-BC-3781-3102 
 
 
V3.0:  17-Mar-2016 
Page 41 of 102 
Confidential Information 
1.5.2 
Efficacy 
The efficacy of lefamulin in humans has been demonstrated in a Phase 2 study of 
207 subjects with ABSSSI comparing 2 lefamulin doses (100 mg and 150 mg IV) with 
vancomycin (≥ 1000 mg) over 5-14 days.  This study enrolled subjects with moderate to 
severe skin infection, excluding any subjects with minor and uncomplicated infection.  In 
total, 90.8 % of subjects in the modified ITT population had S. aureus infection; 69.1 % of 
subjects had MRSA.  
In all populations evaluated, lefamulin 100 mg (IV) and 150 mg (IV) demonstrated 
consistently high clinical and microbiological success rates at several time points including 
the Early Clinical Response visit (Day 3) and Test of Cure (TOC), and 7 to 14 days after the 
completion of therapy (modified ITT population: 82.0 % and 82.4 % for 100 mg and 150 mg 
q12h treatment arms, respectively; 82.4 % for vancomycin).   
There were no significant differences in clinical success rates and microbiological 
eradication rates when assessed by baseline pathogen, particularly S. aureus and MRSA.  
Furthermore, no development of decreasing susceptibility was observed for lefamulin during 
the study (Paukner et al., 2012; Prince et al., 2013; Rubino et al., 2015).  
1.5.3 
Safety 
No changes in safety laboratory parameters, blood pressure (BP), heart rate (HR), or body 
temperature in any subject at any session in any study were of clinical concern.  After IV 
administration, pain and erythema at the infusion site were the most frequently reported 
findings.  The oral administration of lefamulin was generally well tolerated; infrequent mild 
and reversible gastrointestinal findings (nausea, abdominal pain and diarrhea) were reported.  
There were no systemic AEs of clinical concern and no drug-related SAEs in any study 
conducted to date.  None of the subjects met withdrawal or stopping criteria.    
In the Phase 2 study in subjects with ABSSSI, lefamulin (100 mg and 150 mg) administered 
intravenously over 5 to 14 days was generally well tolerated.  The incidence of treatment-
emergent adverse events (TEAEs) considered related to study drug was comparable across 
lefamulin treatment arms (34 % and 39 % in the 100 and 150 mg groups, respectively) versus 
subjects treated with vancomycin (53 %).  The types of TEAEs were consistent with a subject 
population under treatment for ABSSSI.  The most frequently reported treatment-related 
TEAEs in subjects receiving lefamulin were headache, nausea, and diarrhea.  Phlebitis at the 
infusion site was reported in 4 subjects in the lefamulin 100 mg group and 2 subjects in the 
150 mg group.  There was no increased incidence of phlebitis with increased dose.  The most 
frequently reported treatment-related TEAEs for the vancomycin group were headache, 
nausea, pruritus, generalized pruritus, and diarrhea.  All other related TEAEs were reported 
by 3 or fewer subjects in each treatment group.   
In the Phase 2 study, study drug was discontinued due to an AE for 6 subjects (8 events).  
These AEs were hyperhidrosis, vomiting, headache, respiratory failure (an SAE), cellulitis, 
infusion site pain, and dyspnea in the lefamulin groups; and drug eruption in the vancomycin 
group.  Six of these 8 events were considered related to study drug (hyperhidrosis, vomiting, 

Nabriva Therapeutics AG 
Clinical Protocol NAB-BC-3781-3102 
 
 
V3.0:  17-Mar-2016 
Page 42 of 102 
Confidential Information 
headache, infusion site pain, and dyspnea in the lefamulin groups and drug eruption in the 
vancomycin group).  Five subjects experienced an SAE; none was considered related to study 
drug.  These SAEs were abscess, respiratory failure, and cellulitis in the lefamulin groups; 
and accidental overdose (narcotics) and convulsion in the vancomycin group (Prince et al., 
2013). 
The effect of lefamulin on the cardiac conduction parameters of RR, QT, and QTcF has been 
closely monitored in all clinical studies.  A Cmax-dependent, predictable, and reproducible 
prolongation of the QT/QTcF interval has been observed.  A thorough analysis of ECGs in 
the Phase 2 study demonstrated that lefamulin prolonged cardiac depolarization and 
repolarization duration, but otherwise had a similar cardiac safety profile to that of 
vancomycin based on evaluations of 12-lead ECGs.  Therefore, it is expected that lefamulin 
will not produce large effects on cardiac de- and repolarization duration.  No drug-related 
cardiac AE — such as increase in ectopic ventricular activity or other cardiac arrhythmia — 
or clinically relevant ECG findings was reported during the conduct of the studies.  None of 
the protocol-defined stopping criteria (i.e., QTcF > 500 ms and ΔQTcF > 60 ms) was reached 
in any clinical study.  
In summary, the results of the Phase 2 study provide the first proof of concept for the 
systemic use of a pleuromutilin antibiotic in subjects and support the further clinical 
evaluation of lefamulin for therapy of serious infections.  Pharmacokinetic/ 
pharmacodynamic analyses suggest that lefamulin 150 mg IV q12h is an efficacious dosing 
regimen for Phase 3 studies.  Based on available safety data, lefamulin 150 mg IV q12h 
produced therapeutic exposures and demonstrated an acceptable benefit/risk profile for the 
treatment of infected subjects.  Oral doses of 600 mg lefamulin produced similar systemic 
exposures to 150 mg IV with a similar benefit/risk profile and were well tolerated in Phase 1 
studies with no signs or symptoms of clinical concern.  
This is the first Phase 3 study to be conducted in subjects with CABP to be treated only with 
oral administration of pleuromutilin antibiotic.  Subjects will receive treatment with either 
lefamulin or moxifloxacin, a standard of care treatment for CABP.  
2 
STUDY OBJECTIVES 
2.1 Primary Objectives 
• Demonstrate the non-inferiority (NI) of lefamulin versus comparator with respect to the 
Early Clinical Response (96 ± 24 hours after the first dose of study drug) in the 
Intent-to-Treat (ITT) Analysis Set (FDA endpoint). 
• Demonstrate the NI of lefamulin versus comparator with respect to the Investigator’s 
Assessment of Clinical Response at Test of Cure (TOC) (i.e., 5-10 days after the last dose 
of study drug) in the modified-ITT (mITT) and Clinically Evaluable at TOC (CE-TOC) 
Analysis Sets (EMA endpoint). 

Nabriva Therapeutics AG 
Clinical Protocol NAB-BC-3781-3102 
 
 
V3.0:  17-Mar-2016 
Page 43 of 102 
Confidential Information 
2.2 Secondary Objectives 
• Evaluate the Early Clinical Response in the Microbiological Intent-to-Treat (microITT) 
Analysis Set.   
• Evaluate the Investigator’s Assessment of Clinical Response at TOC in the microITT and 
Microbiologically Evaluable at TOC (ME-TOC) Analysis Sets. 
• Evaluate the By-Pathogen Microbiologic Response at TOC in the microITT and ME-
TOC Analysis Sets. 
• Evaluate the safety and tolerability of lefamulin versus comparator in the Safety Analysis 
Set. 
• Evaluate 28 day all-cause mortality in the ITT Analysis Set. 
2.3 Additional Objectives 
• Evaluate the Early Clinical Response by baseline pathogen in the microITT Analysis Set. 
• Evaluate the Investigator’s Assessment of Clinical Response at the End of Treatment 
(EOT) (i.e., within 2 days after the last dose of study drug) and at LFU in the mITT and 
CE Analysis Sets (CE-EOT for IACR at EOT and CE-LFU for IACR at LFU). 
• Evaluate the Investigator’s Assessment of Clinical Response by baseline pathogen at 
TOC and LFU in the microITT and ME Analysis Sets (ME-TOC for IACR at TOC and 
ME-LFU for IACR at LFU). 
• Evaluate the By-Subject Microbiologic Response at TOC in the microITT and ME-TOC 
Analysis Sets. 
• Evaluate the Early Clinical Response PLUS improvement in vital signs in the ITT 
Analysis Set. 
• Evaluate the plasma pharmacokinetics (PK) of lefamulin and its main metabolite, 
BC-8041, in the PK Analysis Set. 
• Explore a variety of health utilization variables and an investigational patient reported 
outcome (PRO) measure in subjects receiving lefamulin compared with subjects 
receiving comparator. 
 
3 
STUDY DESIGN 
This multicenter, multinational, randomized, double-blind, double-dummy, active-controlled 
efficacy and safety study in subjects with CABP will be conducted at approximately 160 
centers.  The planned enrollment is 738 subjects (369 subjects in the lefamulin group and 369 
subjects in the moxifloxacin group) with PORT Risk Class II, III, or IV.  Eligible subjects 
will be randomized 1:1 to lefamulin or moxifloxacin, using an interactive response 
technology (IRT).  Subject randomization will be stratified according to PORT Risk Class 
(Risk Class II vs. III/IV), geographic region (US vs. ex-US), and prior (single dose) short-
acting antibiotic therapy for CABP vs. none.   

Nabriva Therapeutics AG 
Clinical Protocol NAB-BC-3781-3102 
 
 
V3.0:  17-Mar-2016 
Page 44 of 102 
Confidential Information 
Subjects will be consented for the study prior to study assessments being performed and 
confirmation of eligibility (see Section 4).  Screening assessments will be performed within 
24 hours before first dose of study drug.   
Subjects will be assessed for response at the following time points during the study: 
• Early Clinical Assessment (ECA):  96 ± 24 hours after the first dose of study drug. 
• End of Treatment (EOT):  within 2 days after the last dose of study drug (NOTE: every 
attempt should be made to conduct the EOT visit within 1 day after the last dose of study 
drug.  However, if this is not logistically feasible [e.g., visit would need to be conducted 
over a weekend], then conducting the visit within 2 days is acceptable.). 
• Test of Cure (TOC):  5-10 days after the last dose of study drug. 
• Late Follow Up (LFU):  Day 30 (±3 days). 
 
As discussed in detail in Section 6.11, assessment of the 4 cardinal symptoms of CABP 
(dyspnea, cough, purulent sputum production, and chest pain) will be conducted daily; an 
assessment at 96 ± 24 hours after the first dose of study drug will determine Early Clinical 
Response (ECR) (as defined in the Primary Objective - FDA).  NOTE:  ECR will be 
determined programmatically based upon the Investigator’s assessment of the 4 cardinal 
symptoms of CABP; the decision to maintain the subject on study drug therapy will be made 
by the Investigator, based on all available data and his or her best clinical judgment.  In 
addition, as discussed in Section 6.12, the Investigator’s Assessment of Clinical Response 
(IACR) will be performed at the EOT, TOC and LFU visits (Success, Failure and 
Indeterminate at EOT and TOC; Sustained Success, Relapse and Indeterminate at LFU).   
Microbiological assessments will be performed at Screening, and throughout the study as 
clinically indicated (see Section 6.15).  Samples will be taken for Gram’s staining, for 
diagnostic tests (serology, urine antigen tests, molecular tests), and for culture and 
antimicrobial susceptibility testing.  Subjects who have confirmed S. aureus bacteremia must 
be withdrawn from the study.   
Safety will be assessed by monitoring vital signs and oxygen saturation, ECG measurements, 
safety laboratory parameters, and recording of adverse events (AEs) (see Sections 6.5, 6.4, 
6.13, and 7).  A Data Monitoring Committee (DMC) will review the safety data throughout 
the study (see Section 10.2).  
Blood samples for PK analyses will be collected from all subjects (see Section 6.14).  
Exploratory evaluation of a variety of health utilization variables (e.g., length of hospital 
stay, duration of antibiotic therapy, discharge status, discharge destination) as well as a PRO 
instrument (SF-12) will be administered.  The schedule of study procedures and an overview 
of study designs are provided in the synopsis (Table 1. Schedule of Assessments and 
Procedures and Figure 1. Study Design Overview). 

Nabriva Therapeutics AG 
Clinical Protocol NAB-BC-3781-3102 
 
 
V3.0:  17-Mar-2016 
Page 45 of 102 
Confidential Information 
3.1 Study Rationale 
Lefamulin (BC-3781), a semi-synthetic pleuromutilin, represents a new class of antibiotics 
for systemic use in the treatment of bacterial infections in humans.  Based on the antibacterial 
spectrum, safety and tolerability and PK in several Phase 1 and Phase 2 clinical studies, 
lefamulin should be a viable option for the treatment of CABP.  The adverse event profile 
observed in Phase 1 and 2 studies conducted to date demonstrates that lefamulin is well 
tolerated when administered IV at single doses up to 400 mg and q12h dosing for up to 
10 days.  Also, the oral safety profile observed in studies conducted to date demonstrates that 
600 mg of lefamulin is well tolerated when administered as single and repeat doses.  In the 
first study in which a systemically available pleuromutilin antibiotic was administered to a 
patient population, Study NAB-BC-3781-2001, lefamulin was found to be safe and effective 
in treating skin and skin structure infections and supported the continued clinical evaluation 
of lefamulin for serious infections.  In animal models of lung infections caused by 
S. pneumoniae or S. aureus, lefamulin showed enhanced activity when compared to the 
outcome in the murine thigh infection model.  Tissue distribution studies in healthy 
volunteers showed rapid lefamulin distribution, achieving therapeutic exposures in relevant 
target tissues for the treatment of both respiratory tract and skin infections.  Following a 
single 150 mg IV infusion, lefamulin showed higher exposure in epithelial lining fluid (ELF) 
as compared to the penetration into skin tissues (Zeitlinger et al., 2016).  Lefamulin is 
therefore being examined further in subjects with CABP. 
This study will examine whether lefamulin is non-inferior to moxifloxacin for the treatment 
of CABP in adults ≥ 18 years of age.  The comparison between lefamulin and comparator 
will be made with respect to the following assessments:  ECR (96 ± 24 hours after the first 
dose of study drug), as well as IACR at TOC.  The study will also compare safety between 
treatment groups and evaluate PK parameters of lefamulin in this population.  
This protocol is designed to address both the FDA and European Medicines Agency (EMA) 
regulatory requirements for the development of antibacterial agents to treat CABP, which 
differ regarding the preferred primary endpoint.  The EMA supports assessment of clinical 
response by Investigators at a test of cure (TOC) visit, while the FDA adopted assessment of 
clinical signs and symptoms of CABP on Days 3 to 5 as the recommended primary endpoint.  
To adequately accommodate these differences, 2 separate regional Statistical Analysis Plans 
(SAPs) will be utilized to analyze the data collected during this study.   
4 
STUDY POPULATION 
4.1 Inclusion Criteria  
Each subject must: 
1. Be male or female ≥ 18 years of age. 
2. Provide written informed consent and be willing and able to adhere to the study-specified 
procedures and restrictions.  NOTE:  Consent may be provided by the subject’s legally 
authorized representative in accordance with local regulations. 

Nabriva Therapeutics AG 
Clinical Protocol NAB-BC-3781-3102 
 
 
V3.0:  17-Mar-2016 
Page 46 of 102 
Confidential Information 
3. Have an acute illness (≤ 7 days duration) with at least 3 of the following symptoms 
consistent with a lower respiratory tract infection (new or worsening): 
• Dyspnea. 
• New or increased cough. 
• Purulent sputum production. 
• Chest pain due to pneumonia. 
4. Have at least 2 of the following vital sign abnormalities:  
• Fever (body temperature > 38.0 °C (100.4 °F) measured orally or equivalent 
temperature from an alternate body site) or hypothermia (body temperature < 35.0 °C 
(95.0 °F) measured orally or equivalent temperature from an alternate body site). 
• Hypotension (systolic blood pressure < 90 mmHg). 
• Tachycardia (heart rate > 100 beats/min). 
• Tachypnea (respiratory rate > 20 breaths/min). 
5. Have at least 1 other clinical sign or laboratory finding of CABP: 
• Hypoxemia (i.e., O2 saturation < 90 % on room air or while receiving supplemental 
oxygen at subject’s baseline requirement or PaO2 < 60 mmHg). 
• Auscultatory and/or percussion findings consistent with pneumonia (e.g., crackles, 
egophony, dullness). 
• White blood cell (WBC) count > 10 000 cells/mm3 or < 4 500 cells/mm3 or >15 % 
immature neutrophils (bands) regardless of total WBC count. 
6. Have radiographically-documented pneumonia within 48 hours before enrollment (i.e., 
infiltrates in a lobar or multilobar distribution or diffuse opacities on chest x-ray or chest 
computed tomography scan consistent with acute bacterial pneumonia). 
7. Have a Pneumonia Outcomes Research Team (PORT) Risk Class of II, III, or IV and be 
an appropriate candidate for oral antibiotic therapy as treatment for the current episode of 
CABP. 
8. If female, meets the following criteria: 
• Surgically sterile or ≥ 2 years postmenopausal, or if of childbearing potential 
(including being < 2 years postmenopausal), has a negative pregnancy test, and if 
participating in sexual activity that may lead to pregnancy, agrees to use an effective 
dual method of contraception (e.g., condom plus diaphragm, condom plus spermicide, 
intrauterine device plus spermicide) during the study and for ≥ 28 days after the last 
dose of study drug.  If a male partner has been surgically sterile for ≥ 1 year, a single 
contraception method may be used.  NOTE:  The use of contraceptives containing 
progesterone is not permitted. 
• Agrees not to breastfeed during the study and through ≥ 28 days after the last dose of 
study drug. 

Nabriva Therapeutics AG 
Clinical Protocol NAB-BC-3781-3102 
 
 
V3.0:  17-Mar-2016 
Page 47 of 102 
Confidential Information 
9. If male, meets the following criteria: 
• If not surgically sterile and if participating in sexual activity that may lead to 
pregnancy, agrees to use an effective dual method of contraception (e.g., condom plus 
diaphragm, condom plus spermicide, intrauterine device plus spermicide, oral 
contraceptive plus condom) during the study and through ≥ 28 days after the last dose 
of study drug.  If surgically sterile for ≥ 1 year, a single contraception method may be 
used. 
 
4.2 Exclusion Criteria   
Each subject must NOT: 
1. Have received more than a single dose of a short-acting oral or IV antibacterial for CABP 
within 72 hours before randomization (See Appendix 2).   
• EXCEPTION:  Subjects who have received > 48 hours of prior systemic antibacterial 
therapy for the current episode of CABP with unequivocal clinical evidence of 
treatment failure (i.e., worsening signs and symptoms) and isolation of an organism 
from blood or respiratory tract that is resistant to the prior systemic antibacterial 
therapy provided the organism is not resistant to fluoroquinolones. 
2. Require concomitant systemic antibacterial therapy potentially effective against CABP 
pathogens (See Section 6.9). 
3. Have been hospitalized for 2 or more days within 90 days prior to the onset of symptoms 
or have resided in a nursing home or long-term healthcare facility within 30 days prior to 
the onset of symptoms.  NOTE:  Residence in an independent living facility is permitted. 
4. Have confirmed or suspected CABP caused by a pathogen known to be resistant to any of 
the study drugs (e.g., MRSA, Pseudomonas aeruginosa, any pathogen of the 
Enterobacteriaceae Family) or attributable to etiologies other than community-acquired 
bacterial pathogens (e.g., ventilator-associated pneumonia, hospital-acquired bacterial 
pneumonia, bacterial aspiration pneumonia, Pneumocystis jiroveci pneumonia or other 
fungal pneumonia, viral or mycobacterial infection of the lung). 
5. Have a noninfectious cause of pulmonary infiltrates (e.g., pulmonary embolism, chemical 
pneumonitis from aspiration, hypersensitivity pneumonia, congestive heart failure, 
bronchial obstruction, lung cancer, cystic fibrosis). 
6. Have confirmed or suspected pleural empyema (does not include sterile parapneumonic 
effusions). 
7. Have or be at risk for major cardiac events or dysfunction including, but not limited to, 
the following: 
• Known prolonged QT interval or family history of long QT syndrome 
• Clinically significant hypokalemia which has not been treated prior to randomization 
• Clinically unstable cardiac disease, including: unstable atrial fibrillation, symptomatic 
bradycardia, unstable congestive heart failure, active myocardial ischemia, or 
indwelling pacemaker 

Nabriva Therapeutics AG 
Clinical Protocol NAB-BC-3781-3102 
 
 
V3.0:  17-Mar-2016 
Page 48 of 102 
Confidential Information 
• Complete left bundle branch block 
• Receipt within 7 days before enrollment of Class IA or Class III anti-arrhythmic 
medication or, in the opinion of the Investigator, subject may require such medication 
during the study. (Class 1A: Quinidine, Procainamide, Disopyramide; Class III: 
Amiodarone, Dofetilide, Ibutilide, Sotalol) 
• Receipt within 7 days before enrollment of medication that has the potential of 
prolonging the QT interval or, in the opinion of the Investigator, subject may require 
such medication during the study (see Appendix 5). 
8. Be receiving a strong p-glycoprotein inhibitor or a strong CYP3A inducer or inhibitor 
(see Appendix 4). 
9. Have a history of tendon disease/disorder, myasthenia gravis, or known or suspected 
central nervous system (CNS) disorders (severe cerebrovascular arteriosclerosis, 
epilepsy, or other risk factors that may predispose to seizures).   
10. Have a history of any hypersensitivity or allergic reaction to any fluoroquinolone, or any 
drug in the pleuromutilin class (i.e., retapamulin). 
11. Have severely impaired renal function, defined as estimated creatinine clearance (CrCl) 
≤30 mL/min as calculated by the Cockcroft-Gault formula. 
12. Have evidence of significant hepatic, hematologic, or immunologic disease including any 
of the following:  
• Known acute hepatitis, including acute viral hepatitis. 
• Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) level > 5 times 
the upper limit of normal (ULN),  
• Total bilirubin > 3 times the ULN (unless known Gilbert’s disease). 
• Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) level > 3 times 
the upper limit of normal (ULN) and total bilirubin > 2 times the ULN. 
• History of cirrhosis of the liver. 
• Manifestation of end-stage liver disease, such as ascites or hepatic encephalopathy. 
• Current or anticipated neutropenia (<500 neutrophils/mm3). 
• Thrombocytopenia (<50,000 platelets/mm3). 
• Known infection with human immunodeficiency virus and a CD4 count < 200/mm3. 
13. Have known severe immunosuppression, including but not limited to receipt of 
corticosteroid therapy (≥20 mg of prednisone/day or equivalent for >4 weeks) within the 
previous 8 weeks; solid organ or bone marrow transplantation within the previous 12 
months; or currently receiving cytotoxic chemotherapy. 
14. Have a life expectancy of ≤ 3 months because of any disease other than the current 
episode of CABP (e.g., current or impending respiratory failure, acute heart failure, 
shock, acute coronary syndrome, unstable arrhythmia, hypertensive emergency, clinically 

Nabriva Therapeutics AG 
Clinical Protocol NAB-BC-3781-3102 
 
 
V3.0:  17-Mar-2016 
Page 49 of 102 
Confidential Information 
relevant gastrointestinal bleeding, profound metabolic abnormality, or acute 
cerebrovascular event). 
15. Have participated in any study involving administration of an investigational agent or 
device within 30 days or ≤ 5 terminal elimination half-lives of the previous 
investigational medicinal product, whichever is longer, before enrollment. 
16. Have been previously treated with lefamulin or previously enrolled in this study. 
17. Have any condition that, in the opinion of the Investigator, would compromise the safety 
of the subject or the quality of the data. 
 
5 
STUDY DRUG ADMINISTRATION 
See Section 8 for a complete description of study drugs.  Instructions for the preparation of 
study drugs will be provided in a Pharmacy Manual. 
5.1 Selection of Lefamulin Doses 
This is the first study of an all oral regimen of lefamulin in subjects with CABP.  Based on 
results obtained from in vitro, animal and human experiments conducted to date, lefamulin is 
predicted to be well tolerated and efficacious in CABP.  To further explore and validate these 
findings, a pharmacometric approach was employed to assess a lefamulin dosing regimen of 
150mg IV q12h for the treatment of subjects with CABP caused by S. pneumoniae or 
S. aureus.  This approach has been utilized previously to support dose selection decisions in 
antibacterial drug development (Bhavnani et al., 2005; Bhavnani et al., 2009; Van Wart et al., 
2009).  An oral dose of 600 mg q12h (also being used in the IV-to-Oral Phase 3 study, NAB-
BC-3781-3101) has been shown to provide similar exposure (e.g., AUC) as the 150 mg IV 
dose.  Since the primary PD driver of lefamulin efficacy is total drug exposure (AUC), 
600 mg q12h given as an oral tablet is expected to provide equivalent therapeutic coverage as 
the 150 mg IV q12h regimen.  
A population PK model describing the disposition of lefamulin, non-clinical PK/PD targets 
for lefamulin activity against S. pneumoniae and S. aureus (derived from robust surveillance 
data for both pathogens), and Monte Carlo simulation were utilized to carry out PK/PD target 
attainment analyses. 
The population PK model used to conduct Monte Carlo simulations was developed using PK 
data from 11 Phase 1 studies of subjects who received IV or oral lefamulin and 1 Phase 2 
study of infected subjects with ABSSSI who received IV lefamulin.  Importantly, this dataset 
includes data describing the disposition of lefamulin in epithelial lining fluid (ELF) (obtained 
from a Phase 1 study; the relevant site for treatment of CABP) as well as in subjects 
experiencing active infection (the Phase 2 ABSSSI study).  Thus, the data used to construct 
the population PK model, the parameter estimates and associated variability incorporated into 
the Monte Carlo simulations are reflective of patients with CABP.  
Non-clinical PK/PD targets were identified using PK/PD relationships for efficacy derived 
from data from a neutropenic murine-lung infection model.  For these analyses, focus was 

Nabriva Therapeutics AG 
Clinical Protocol NAB-BC-3781-3102 
 
 
V3.0:  17-Mar-2016 
Page 50 of 102 
Confidential Information 
given to median 24 h AUC ELF/MIC ratio targets for S. pneumoniae and S. aureus associated 
with a 1-log10 CFU reduction from baseline as it has been demonstrated that patients with 
CABP who attain a 1-log10 CFU reduction from baseline have a higher rate of successful 
response compared to those patients who did not attain such PK/PD targets.  Lastly, in order 
to make inferences about dose for patients with S. pneumoniae or S. aureus bacteremia 
arising from CABP, the above-described analyses were also carried out using 24 h 
fAUC/MIC ratio targets for a 1-log10 CFU reduction from baseline efficacy for both 
pathogens.  The MIC distributions utilized were based on large, contemporary isolate 
libraries that represent > 1400 S. pneumoniae and > 5500 S. aureus isolates, accrued globally.  
Based on pharmacokinetic data derived from subjects receiving lefamulin 600 mg orally in 
the fasted state, the percent probabilities of attaining the median AUCELF/MIC ratio targets 
associated with a 1-log10 CFU reduction from baseline by MIC were >95 % at a MIC of 
0.5 µg/mL for S. pneumoniae and >97 % at a MIC of 0.25 µg/mL for S. aureus.  In the fed 
state (i.e. when subjects ingest a high-calorie, high-fat meal), the percent probabilities of 
achieving similar AUCELF/MIC ratio targets were >85% and >91% for S. pneumoniae and 
S. aureus, respectively.  Based upon these analyses, oral lefamulin will be administered in the 
current study either 1 hour before a meal or 2 hours after a subject ingests a meal to mitigate 
against any potential negative effect associated with co-administration with food. 
The results obtained from PK/PD target attainment analyses using a population PK model 
describing the disposition of lefamulin, non-clinical PK/PD targets for lefamulin against 
S. pneumoniae and S. aureus, robust surveillance data, and Monte Carlo simulation support 
the selection of lefamulin 600 mg PO q12h as well-tolerated, having a high probability of 
efficacy and an appropriate dosing regimen to be studied for the treatment of adult subjects 
with CABP.   
5.2 Selection of Comparator 
The Infectious Diseases Society of America (IDSA)/American Thoracic Society (ATS) 
treatment guidelines recommend the use of an anti-pneumococcal fluoroquinolone for 
hospitalized patients (not in the ICU) with CABP.  The guidelines also recommend a 
fluoroquinolone for outpatients with certain co-morbid conditions, outpatients who have used 
antimicrobials in the previous few months, and outpatients in regions with high rates of 
macrolide-resistant S. pneumonia regardless of co-morbidities or prior antibiotic use.  The 
European Society of Clinical Microbiology and Infectious Diseases also supports the use of 
fluoroquinolones for outpatient treatment of CABP in areas with increased bacterial 
resistance rates to tetracyclines and macrolides, as well as for empiric therapy in hospitalized 
patients with CABP.  These guidelines also note that respiratory quinolones may offer 
advantages over other therapy options for Legionella infection and that moxifloxacin has the 
highest antipneumococcal activity. 
Therefore, in order to provide a robust comparison of oral lefamulin to an oral CABP 
treatment regimen that would be appropriate in multiple regions and in patients with and 
without co-morbidities, respiratory fluoroquinolones were considered the comparator of 
choice.  Moxifloxacin was chosen over other respiratory fluoroquinolones because the labels 
of other fluoroquinolones have variable dose and/or treatment durations for CABP depending 

Nabriva Therapeutics AG 
Clinical Protocol NAB-BC-3781-3102 
 
 
V3.0:  17-Mar-2016 
Page 51 of 102 
Confidential Information 
on the specifics of approved labels in other countries.  In addition, other respiratory 
fluoroquinolones require adjustment in settings of renal dysfunction which would complicate 
treatment regimens and create challenges with maintaining the blind.    
5.3 Randomization 
Qualified subjects will be randomized to receive lefamulin or moxifloxacin in a 1:1 
allocation ratio.  Randomization may occur following the required assessments and prior to 
administration of the first dose of study drug. 
Randomization will be stratified by PORT Risk Class (Risk Class II vs. III and IV; see 
Section 6.3), geographic region (US vs. ex-US), and prior (single dose) short-acting 
antibiotic therapy for CABP vs. none using blocked randomization via IRT.  (NOTE:  No 
more than 25 % of randomized subjects will have received a single dose of a short-acting 
antibiotic).  A minimum of 50% of the total number of subjects randomized will have a 
PORT Risk Class of III or IV.   
The randomization schedule will be generated by Nabriva (or designee).  Subjects 
randomized into the study will be assigned the treatment corresponding to the next available 
number in the respective stratum of the computer-generated randomization schedule.  Prior to 
dosing, study personnel will contact the IRT system to obtain a treatment assignment.  
Subjects are considered randomized once a randomization number has been assigned 
regardless of whether the subject receives study drug.  Randomized subjects who do not 
receive study drug or who discontinue participation in the study for any reason will not be 
replaced.   
5.4 Study Drug Treatment 
The duration of blinded study drug administration will be 7 days.   
Subjects randomized to lefamulin will receive oral lefamulin 600 mg q12h for 5 days 
(10 doses) and oral moxifloxacin placebo q24h for 7 days (7 doses).  Subjects randomized to 
moxifloxacin will receive oral moxifloxacin 400 mg q24h for 7 days (7 doses) and oral 
lefamulin placebo q12h for 5 days (10 doses).   
On Day 1, study personnel will administer the first dose of study drug at the study site to all 
subjects, as soon as possible after the diagnosis of CABP and completion of all required 
Day 1 procedures as outlined in Table 1.  While subjects are hospitalized, all doses of study 
drug will be administered by hospital staff or study personnel.   
For Outpatients, or in the event a subject is discharged from the hospital during the study 
drug administration period, an adequate supply of study drug will be dispensed for self-
administration at home.  Subjects will be provided instructions regarding the dosing 
schedule.  Subjects may self-administer oral study drug at home with the following 
exception:  Study personnel will advise subjects who are Outpatients that they must return to 
the study site to assess CABP signs and symptoms at 96 ± 24 hours after the first dose of 
study drug (see Section 6.11).  Study personnel will inform Outpatients as to the timing of 

Nabriva Therapeutics AG 
Clinical Protocol NAB-BC-3781-3102 
 
 
V3.0:  17-Mar-2016 
Page 52 of 102 
Confidential Information 
this required study site visit.  Subjects will be advised not to take their first dose of study 
drug at home that day, rather to bring their blister packs (used and unused) to the study site 
where they will take their dose while supervised, so that specific assessments can be 
performed both prior to and after taking the dose (see Sections 6.4 [ECGs] and 6.14 [PK]). 
On Study Day 1, if q12h dosing is not feasible, the 1st and 2nd doses may be administered as 
close as 8 hours apart, in order to allow 2 doses to be given on Day 1.  In this circumstance, 
the subject’s dosing schedule should be adjusted on Day 2 to a regular q12h morning and 
evening schedule.  Subsequently, every effort should be made to maintain a q12h dosing 
schedule.  When this is not possible, it is acceptable to administer doses within 4 hours of the 
scheduled dosing time (i.e., a minimum of 8 hours between doses). 
Study drug should be administered at least 1 hour before a meal or 2 hours after a meal.  
However, in the event that a subject has taken any of the following − antacids containing 
aluminum, products containing iron, or multivitamins containing zinc − study drug should be 
administered 2 hours before or 4 hours after consuming any of these medications.  Doses 
should be administered with approximately 240 mL (8 ounces) of water.  
The lot numbers and expiration dates of all study drugs supplied will be recorded. 
5.5 Blinding 
This is a double-blind, double-dummy study.   
The study personnel, Sponsor (except as specified), and subject will not know what study 
drug is being administered.  
Study drugs will be provided in blister packs and all study drug administration will utilize a 
“double-dummy” technique.  Details about the double-dummy design and blinding are 
provided in a Study Procedure Manual.  Lefamulin or matching placebo tablets will be 
provided by the Sponsor.  Moxifloxacin will be over encapsulated; matching placebo tablets 
will also be provided by the Sponsor.   
A member(s) of the Sponsor’s Clinical Pharmacology group (or designee) will be unblinded 
to treatment assignment, as appropriate, in order to perform PK/PD assessments.  A Data 
Monitoring Committee (DMC) will review study data by masked treatment group in 
accordance with the DMC Charter.  In addition, as needed to meet regulatory reporting 
requirements on a country-by-country basis, designated pharmacovigilance personnel may be 
unblinded to treatment status of individual patients.  In this circumstance, and if there are no 
other concerns, neither the Sponsor nor study personnel will be unblinded to treatment status.   
5.6 Unblinding of Therapy Assignments 
Unblinding of therapy assignment may be requested in an emergency if unblinding is 
considered necessary for medical management of the subject.  In such a case, the Investigator 
must contact the Sponsor (or designee) and document the reason(s) for the request to unblind.   

Nabriva Therapeutics AG 
Clinical Protocol NAB-BC-3781-3102 
 
 
V3.0:  17-Mar-2016 
Page 53 of 102 
Confidential Information 
The Sponsor (or designee) must document any such communication with an Investigator.  
The IRT system will record the date of any unblinding of individual therapy assignments.   
The study will be unblinded for all analyses after the study database is locked, which will 
occur after the last subject randomized in the study has completed the 30-day post treatment 
follow-up assessment period.   
5.7 Adherence 
If subjects are Inpatient, hospital staff or study personnel will administer all doses of study 
drug and will record the date and time of dosing.  In addition, for Outpatients, any doses 
administered under supervision of study personnel in conjunction with assessments/ 
procedures (e.g., PK sampling, ECGs), study personnel will also record the date and time of 
those doses. 
Outpatient subjects will be instructed to bring all used and unused blister packs to each study 
visit so that drug accountability can be reviewed by study personnel.  Study personnel will 
collect all blister packs (empty or containing unused study drug) at the EOT visit (see Section 
8.3.3).  The total number of pills dispensed on Day 1 and returned at the EOT visit will be 
recorded in the eCRF. 
5.8 Occupational Safety 
Lefamulin and moxifloxacin being used in this study are not expected to pose a significant 
occupational safety risk to study personnel under normal conditions of use and 
administration.  
A Material Safety Data Sheet describing occupational hazards and recommended handling 
precautions either will be provided to the Investigator, where this is required by local laws, or 
is available upon request from Nabriva Therapeutics AG. 
6 
STUDY ASSESSMENTS AND PROCEDURES 
A schedule of study procedures is presented in Table 1.  Subjects meeting the eligibility 
criteria listed in Section 4 may be enrolled in the study after the nature and purpose of the 
protocol have been explained and written informed consent to participate has been 
voluntarily given by the subject or the subject’s legally authorized representative in 
accordance with local regulations.   
Study personnel must complete all screening procedures after informed consent is signed and 
prior to the first dose of study drug.  Note: Assessments performed as part of routine standard 
of care prior to consent (e.g., chest X-ray, blood culture) may be used to satisfy study 
screening requirements; however, no study specific procedures may be performed prior to 
informed consent.   
During the Study Drug Administration Period, the first dose of study drug is counted as 
0 Hour on Day 1.  The Investigator should make every effort to perform procedures at the 

Nabriva Therapeutics AG 
Clinical Protocol NAB-BC-3781-3102 
 
 
V3.0:  17-Mar-2016 
Page 54 of 102 
Confidential Information 
scheduled times and to record the actual time of the procedures, where appropriate, in the 
subject's eCRF.   
For subjects who are screened (i.e., those with signed written informed consent) but who are 
not randomized, the reason for screening failure will be recorded. 
6.1 Inpatient and Outpatient Assessments 
As shown in the Schedule of Assessments and Procedures (see Table 1), the timing of 
assessments and procedures during the Study Drug Administration Period (Days 1-7) may 
differ between subjects who are Inpatient versus Outpatient.   
Hospitalization is not a requirement for this study (i.e., subjects do not need to be admitted to 
the hospital to participate and those who are admitted may be discharged at any time at the 
discretion of the investigator).   
While Inpatient, all assessments and procedures (including daily study drug administration) 
will be conducted at the study site/hospital in accordance with the schedule shown in Table 1 
(Screening/Baseline through LFU).  While Outpatient, the study site must contact the 
subjects by telephone daily to assess CABP signs and symptoms, assess for the presence of 
AEs, and determine changes in concomitant medications (see Sections 6.11, 7, and 6.8.2).   
All subjects, including Outpatients, must be evaluated by at the investigational site by study 
personnel at the following time points/visits:  Screening/Baseline; Day 1; 96 ± 24 hours after 
the first dose of study drug; EOT; TOC; and LFU (see Table 1).  
6.1.1 
Outpatient Visit for ECR Assessment and Other Site Procedures 
Outpatients must return to the site for a face-to-face visit with study personnel 96 ± 24 hours 
(i.e., 72 to 120 hours) after the first dose of study drug.  Study personnel will inform 
Outpatients as to the timing of this required study site visit in the course of the daily 
telephone contacts. 
The purpose of this site visit is to assess CABP signs and symptoms which will be used to 
programmatically determine the ECR, as well as to perform other procedures that cannot be 
done by telephone (i.e., ECG, blood samples for PK analysis, blood samples for safety 
assessments, vital signs, and physical examination).  
ECGs and blood samples for PK analysis must be performed within specified time windows 
before and after study drug administration.  Therefore, it is critical that the subject be 
instructed to not take their first dose of study drug at home that day, rather to bring all their 
blister packs (used and unused) to the study site.  The dose associated with the outpatient 
visit for ECR assessment and other site procedures will be taken under supervision of study 
personnel.  In addition, as discussed in Sections 5.4 and 6.17, study personnel will remind 
subjects regarding adherence to the food and supplement restrictions when scheduling this 
visit.   

Nabriva Therapeutics AG 
Clinical Protocol NAB-BC-3781-3102 
 
 
V3.0:  17-Mar-2016 
Page 55 of 102 
Confidential Information 
6.2 Medical/Surgical History and Physical Examination 
A medical and surgical history will be taken at Screening.  All medical history findings that 
have been present or active within the 5 years prior to enrollment will be entered into the 
eCRF regardless of clinical relevance or presence at study start.  Medical history findings 
that have not been present within the 5 years prior to enrollment will be recorded if deemed 
clinically relevant by the Investigator to the conduct of the study.  The medical history should 
include drug allergy history, past and present smoking status, influenza virus and 
pneumococcal vaccination history, as well as the presence of influenza virus infection during 
the current illness.   
A complete physical examination will be performed by the Investigator at Screening.  At the 
time points specified in Table 1, subsequent directed physical examinations will be 
performed according to standard institutional practices and must be documented in source 
documents. 
Body weight and height will be measured at Screening only.   
6.3 PORT Risk Class Assessment 
Study personnel will determine the subject’s PORT Score (Table 2) and subsequent PORT 
Risk Class (Table 3) at Screening only. 

Nabriva Therapeutics AG 
Clinical Protocol NAB-BC-3781-3102 
 
 
V3.0:  17-Mar-2016 
Page 56 of 102 
Confidential Information 
Table 2. 
PORT Score Determination 
Patient Characteristic 
Point Assignment 
Age 
1 point for each year of age 
Female 
–10 if yes 
Neoplastic disease history 
+30 if yes 
Liver disease 
+20 if yes 
Congestive heart failure 
+10 if yes 
Cerebrovascular disease 
+10 if yes 
Renal disease 
+10 if yes 
Altered mental status 
+20 if yes 
Respiratory rate ≥ 30 breaths/min 
+20 if yes 
Systolic blood pressure < 90 mmHg 
+20 if yes 
Temperature < 35 ºC (95 ºF) or ≥ 40 ºC (104 ºF) 
+15 if yes 
Pulse ≥125 beats/min 
+10 if yes 
pH <7.35 (from ABG) 
+30 if yes 
(+0 if ABG not obtained) 
Blood urea nitrogen > 30 mg/dL (Urea > 11 mmol/L) 
+20 if yes 
Sodium < 130 mmol/L 
+20 if yes 
Glucose ≥ 250 mg/dL (≥14 mmol/L) 
+10 if yes 
Hematocrit < 30 % 
+10 if yes 
Partial pressure of arterial O2 < 60 mmHg (from ABG if 
medically indicated) or O2 saturation < 90 % (by pulse 
oximetry) 
+10 if yes 
Pleural effusion on radiograph 
+10 if yes 
 
 
 
PORT SCORE 
Sum of Applicable Numbers 
Above 
 
Table 3. 
PORT Risk Class Determination 
PORT Risk Class 
PORT Score 
I (Ineligible for Study) 
0-50 
II  
51-70 
III 
71-90 
IV 
91-130 
V (Ineligible for Study) 
> 130 
 

Nabriva Therapeutics AG 
Clinical Protocol NAB-BC-3781-3102 
 
 
V3.0:  17-Mar-2016 
Page 57 of 102 
Confidential Information 
6.4 Electrocardiograms 
Triplicate 12-lead ECGs will be performed within a 5-minute interval at time points specified 
in Table 1.  The subject should be stabilized in a supine position for 5 minutes before 
recording the ECG.  ECG recordings should allow a full assessment of QT intervals.  
Machine-read values for QTc/QTcF will be evaluated for determination of eligibility at 
Screening.  If the quality of the ECG is insufficient then it must be repeated.  All ECG data 
must be reviewed by the Investigator or designee and any findings of clinical significance 
found following Screening will be recorded as AEs in the eCRF.  In addition, advice may be 
sought from appropriate cardiologists, if necessary.  ECGs will be made available to the 
Sponsor for review and will be sent to a Cardiac Core Laboratory for further evaluation.  
If Screening and Day 1 are on the same day, the Screening ECG can serve as the Day 1 ECG 
prior to the first dose of study drug; an additional ECG must be performed 1-3 hours after 
administration of first dose.   
On Day 4 (Inpatients) or 96 ± 24 hour post first dose (Outpatients), ECGs in triplicate are 
required prior to the first dose of study drug and again within 1-3 hours after the first dose of 
study drug.  Thus, Outpatients will be advised not to take their first dose of study drug at 
home that day, rather to bring their blister packs (used and unused) to the study site where 
they will take their dose while supervised so that the ECGs can be performed both prior to 
and after taking the dose.  
As discussed in detail in Section 6.18.3, if at any time the subject demonstrates an average 
QTcF value > 500 ms (mean of 3 ECGs at any time point), or an average QTcF value 
> 480 ms with a concurrent increase in average QTcF value of > 60 ms (mean of 3 post-dose 
ECGs compared to mean pre-dose ECG’s taken on that day) study drug will be discontinued.   
6.5 Vital Signs and Oxygen Saturation 
Vital signs (HR, BP, respiratory rate and body temperature) and oxygen saturation will be 
recorded at time points specified in Table 1.  Blood pressure and heart rate assessments will 
be performed according to standard practice at the clinical sites.  Vital signs associated with 
the highest temperature after the first dose of study drug will be recorded in the eCRF.   
In addition, if the subject is receiving supplemental oxygen therapy, the amount given will be 
recorded in the eCRF. 
All subjects will have vital signs and O2 saturation evaluated at Screening/Baseline and 
Day 1.  If screening/baseline and Day 1 occur on the same calendar day, vital signs and O2 
saturation do not need to be repeated.  All subjects will also have assessments at EOT and 
TOC; at LFU, vital signs should be performed if medically indicated.  If EOT and the last 
day of study drug are the same day, vital signs do not need to be repeated, they may be 
recorded once on that day (i.e., as part of the EOT assessment). 
For Inpatients, in addition to the above time points, vital signs and O2 saturation will be 
measured daily and recorded.  If multiple vital signs are taken on a study day, the highest 

Nabriva Therapeutics AG 
Clinical Protocol NAB-BC-3781-3102 
 
 
V3.0:  17-Mar-2016 
Page 58 of 102 
Confidential Information 
temperature and the vital signs associated with that high temperature will be recorded.  For 
Outpatients, in addition to the above time points, vital signs and saturation will be measured 
at the study visit scheduled 96 ± 24 hour after the first dose of study drug (see Section 6.1.1).   
Vital signs measurements are to be repeated if clinically significant changes or machine 
errors occur.  Out of range BP and HR will be repeated at the Investigator’s discretion.  
Semi-supine BP and HR will be measured more frequently if warranted by the clinical 
condition of the subject.   
6.6 Chest X-Ray or CT Scan 
Chest x-ray will be performed at the Screening/Baseline visit as specified in Table 1 and 
evaluated by the Investigator (or designee) to qualify a subject for enrollment; however, the 
imaging study must also be interpreted by a radiologist.  If a chest computed tomography 
scan has been performed within 48 hours of enrollment and demonstrates findings consistent 
with pneumonia, it can be used in place of a chest x-ray.  The test type and date and the 
Investigator’s and radiologist’s reading/interpretation will be recorded in the eCRF.   
6.7 Arterial Blood Gases 
Study sites are not required to measure arterial blood gases (PaO2, PaCO2) or pH.  However, 
if these data are available, they should be recorded in the eCRF.   
6.8 Prior and Concomitant Medications 
Prior and concomitant medications that will be recorded include prescription medications, 
dietary supplements/vitamins, and over-the-counter medications.  Topical medications will 
be recorded only if used as treatment for an AE.  The minimum requirement is that drug 
name, indication and the stop and start dates of administration are to be recorded.  For the 
following agents, the drug dose, route and frequency will also be collected in the eCRF: 
• Systemic antibacterial agents 
• Corticosteroids 
Additionally, for systemic antibacterial agents start time and stop time will be recorded. 
6.8.1 
Prior Medications 
A medication history will be taken at Screening.  All medications taken within 1 week prior 
to Day 1 will be entered into the eCRF. 
6.8.2 
Concomitant Medication 
All concomitant medications taken during the study will be recorded in the subject's eCRF.  
In the case that additional antibiotic treatment is required for the current episode of CABP, 
the subject’s study drug will be discontinued and they will be considered to have an IACR of 

Nabriva Therapeutics AG 
Clinical Protocol NAB-BC-3781-3102 
 
 
V3.0:  17-Mar-2016 
Page 59 of 102 
Confidential Information 
Failure; however, subjects will continue to be followed for safety as detailed in Section 
6.18.1.  
Other systemic antibacterial agents that are potentially effective against pathogens associated 
with CABP should not be administered during the study except in the case of CABP 
treatment failure or when medically necessary for treatment of a concomitant infection.  The 
following antibacterial agents are permitted: 
• Anti-tuberculosis drugs isoniazid, ethambutol and pyrazinamide 
• Cinoxacin 
• Dapsone 
• Enoxacin 
• Fidaxomicin 
• Methenamine Mandelate 
• Metronidazole 
• Naladixic Acid 
• Nitrofurantoin 
• Norfloxacin 
• Oral Vancomycin 
Although all drugs that are metabolized by CYP3A4 are not prohibited, they should only be 
used when necessary and with appropriate subject monitoring.  In vitro studies demonstrated 
that lefamulin may inhibit the metabolism of substrates of CYP3A4; however, results 
obtained from Phase 1 drug interaction studies performed demonstrate that lefamulin has a 
marginal effect on CYP3A4 inhibition in humans and no change in lefamulin’s dose is 
required.  In addition, all drugs that are P-glycoprotein substrates are not prohibited; 
however, they should only be used when necessary and with appropriate subject monitoring. 
A list of drugs that are CYP3A4 substrates and P-glycoprotein substrates is provided in 
Appendix 3.   
Close monitoring is recommended in subjects who require medication that can reduce 
potassium levels (e.g., loop and thiazide-type diuretics, laxatives and enemas [high doses], 
corticosteroids, amphotericin B) or medication that is associated with clinically significant 
bradycardia. 
6.9 Prohibited Medications 
The following medications are prohibited:   
• Prior (within 72 hours before randomization) oral or IV antibacterials for CABP.   
- 
NOTE:  Up to 25 % of subjects may have a single dose of a short-acting antibiotic for 
the current episode of CABP within 72 hours of randomization.   

Nabriva Therapeutics AG 
Clinical Protocol NAB-BC-3781-3102 
 
 
V3.0:  17-Mar-2016 
Page 60 of 102 
Confidential Information 
- 
EXCEPTION:  A subject who has received > 48 hours of prior systemic antibacterial 
therapy for the current episode of CABP with unequivocal evidence of treatment 
failure (i.e., worsening signs and symptoms) and the isolation of an organism from 
blood or respiratory tract that is resistant to the prior systemic antibacterial therapy, 
provided the organism is not resistant to fluoroquinolones. 
• Agents that prolong the QT interval (see Appendix 5) 
• Systemic corticosteroids at a dose ≥ 20 mg per day (prednisone equivalent) 
• Anti-epilepsy or seizure medication 
• Strong p-glycoprotein inhibitors (see Appendix 4) [NOTE:  The use of contraceptives 
containing progesterone is not permitted.] 
• Strong CYP3A inhibitors or inducers (see Appendix 4) 
 
6.10 Nonpharmacologic Treatments and Procedures 
Nonpharmacologic treatments and procedures (e.g., surgical, diagnostic) that occur during 
the study will be entered into the eCRF, including the date and reason for the 
treatment/procedure. 
6.11 Assessment of Clinical Signs and Symptoms of CABP 
Clinical signs and symptoms of CABP will be assessed at the time points specified in 
Table 1.  Signs and symptoms are not obtained at TOC or LFU if the subject previously had 
an IACR of Failure.  
The intensity of each symptom (dyspnea, cough, sputum production, and chest pain) will be 
evaluated and recorded as absent, mild, moderate or severe based on the definitions in 
Table 4 below.  While Inpatient, all subjects will have clinical signs and symptom of CABP 
assessed daily.   
Subjects who are discharged to home will be contacted by phone to assess signs and 
symptoms of CABP daily while on study drug with the following exception:   
All subjects must have a study site visit 96 ± 24 hours after the first dose of 
study drug to assess CABP signs and symptoms.  Study personnel will inform 
Outpatients as to the timing of this required study site visit (see Section 6.1.1).   

Nabriva Therapeutics AG 
Clinical Protocol NAB-BC-3781-3102 
 
 
V3.0:  17-Mar-2016 
Page 61 of 102 
Confidential Information 
Table 4. 
Definitions of Symptom Intensity 
Symptom 
Absent (0) 
Mild (1) 
Moderate (2) 
Severe (3) 
Dyspnea 
Resolution (to pre-CABP 
baseline) or absence of 
dyspnea 
Dyspnea on 
exertion (e.g., 
climbing stairs) 
Dyspnea with 
normal/routine 
activities (e.g., 
walking) 
Dyspnea at rest or 
requiring oxygen 
therapy 
Cough 
Resolution (to pre-CABP 
baseline) or absence of 
cough 
Transient, does 
not interfere with 
normal activity 
Frequent, 
interferes with 
normal activity or 
sleep 
Constant, 
interferes with 
most or all activity 
or sleep 
Production of 
purulent sputum 
Resolution (to pre-CABP 
baseline) or absence of 
sputum production 
Sputum 
production rarely 
causes difficulty 
or distress 
Sputum production 
often causes 
difficulty or 
distress 
Constant difficulty 
with sputum 
production 
Chest pain 
Resolution or absence of 
chest pain related to 
CABP 
Transient, does 
not interfere with 
normal activity 
Frequent, 
interferes with 
normal activity or 
sleep 
Constant, 
interferes with 
most or all activity 
or sleep 
 
The assessment of the clinical signs and symptoms of CABP will be used to determine ECR 
which will be calculated programmatically.  The decision to maintain a subject on study 
drug therapy will be made by the Investigator, based on all available data and his or her best 
clinical judgment.  
Subjects will be programmatically defined as a Responder if the following 4 criteria are met: 
• Alive. 
• Improvement in at least 2 of the 4 cardinal symptoms of CABP the subject presented with 
at Baseline.  Improvement is defined as a decrease by at least 1 level of severity. 
• No worsening of any of the 4 cardinal symptoms of CABP. Worsening is defined as an 
increase by at least 1 level of severity of any symptom. 
• Did not receive a concomitant antibiotic for the treatment of CABP. 
Subjects will be programmatically defined as a Non-Responder if any of the following 
criteria are met: 
• Did not show an improvement in at least 2 of the 4 cardinal symptoms of CABP the 
subject presented with at Baseline. Improvement is defined as a decrease by at least 1 
level in severity; or 
• Worsening of any of the 4 cardinal symptoms of CABP. Worsening is defined as an 
increase by at least 1 level in severity for any symptom; or 
• Received a concomitant antibiotic for the treatment of CABP; or 
• Died from any cause. 

Nabriva Therapeutics AG 
Clinical Protocol NAB-BC-3781-3102 
 
 
V3.0:  17-Mar-2016 
Page 62 of 102 
Confidential Information 
Subjects will be programmatically defined as an Indeterminate if the following criterion is 
met: 
• The symptom data are missing such that a response or non-response cannot be 
determined.  
 
6.12 Investigator’s Assessment of Clinical Response (IACR) 
The Investigator will assess Clinical Response at time points specified in Table 1. 
6.12.1 
Investigator’s Assessment of Clinical Response (IACR) at End of Treatment 
and Test of Cure 
The Investigator’s Assessment of Clinical Response will be classified as Success, Failure or 
Indeterminate at EOT and TOC based on the following criteria: 
• Success:  The subject’s clinical signs and symptoms have resolved or improved such that 
no additional antibacterial therapy is administered for the treatment of the current episode 
of CABP. 
• Failure:  A subject is a treatment Failure if any of the following is met:  
- 
Signs and symptoms of CABP have not resolved, not improved, or have worsened 
such that non-study antibacterial therapy is administered for the treatment of the 
current episode of CABP. 
- 
Measures of inflammation such as temperature or elevated WBC have worsened or 
failed to improve such that non-study antibacterial therapy is administered for the 
treatment of the current episode of CABP. 
- 
Bacteremia has worsened or failed to improve resulting in administration of non-
study antibacterial therapy. 
- 
The occurrence of an AE requiring discontinuation of study drug and institution of 
non-study antibacterial therapy for the treatment of the current episode of CABP. 
- 
Death from any cause.  
• Indeterminate:  Insufficient information is available to determine Success or Failure, 
specifically lost to follow-up. 
NOTE:  Subjects who have an IACR of Failure at EOT will not have an IACR assessed at 
TOC and will be considered to have an IACR of Failure at TOC. 
6.12.2 
Investigator’s Assessment of Clinical Response (IACR) at Late Follow Up 
For subjects who do not have an IACR of Failure at TOC, a determination of Clinical 
Response (Sustained Success, Relapse or Indeterminate) will be made at LFU based on the 
following criteria: 

Nabriva Therapeutics AG 
Clinical Protocol NAB-BC-3781-3102 
 
 
V3.0:  17-Mar-2016 
Page 63 of 102 
Confidential Information 
• Sustained Success:  The subject’s clinical signs and symptoms remain resolved or 
further improved such that no additional antibacterial therapy has been administered for 
the treatment of the current episode of CABP. 
• Relapse:  The subject was a Clinical Success at TOC, however, any of the following are 
met:  
- 
Clinical signs and symptoms of CABP have recurred such that additional non-study 
antibacterial therapy is administered for the treatment of the current episode of 
CABP. 
- 
Measures of inflammation such as temperature or elevated WBC have recurred such 
that additional non-study antibacterial therapy is administered for the treatment of the 
current episode of CABP. 
- 
Recurrent bacteremia resulting in administration of non-study antibacterial therapy. 
- 
Death from any cause. 
• Indeterminate: Insufficient information is available to determine Sustained Success or 
Relapse, specifically lost to follow-up. 
 
6.13 Clinical Laboratory Tests (Safety) 
Safety laboratory tests will be performed at the time points specified in Table 1 and sent to a 
Central Laboratory. Blood samples sent to the local laboratory for the purposes of 
determining study eligibility must be repeated and sent to the central laboratory following 
enrollment.  Blood and/or urine will be collected at LFU only if the subject had an abnormal 
(high/low flag) result at TOC.  Additional tests may be performed at the discretion of the 
Investigator if deemed clinically appropriate.  Subjects treated as outpatients must agree to 
return to the site for blood draws as indicated in Table 1 (i.e., 96 ± 24 hour post first dose [see 
Section 6.1.1], EOT, and TOC visits). 
A full list of the clinical laboratory tests that will be performed and analyzed can be found in 
Appendix 1.  A urine pregnancy test will be performed at the site on all females unless 
surgically sterile or at least 2 years post-menopausal.  A negative urine pregnancy test is 
required prior to randomization.  Serum must be collected on Day 1 prior to 1st dose and sent 
to the central lab for confirmatory testing. 
Any safety laboratory results outside the normal range will be repeated at the discretion of 
the Investigator and will be evaluated by the Investigator or designee as “clinically 
significant” or “not clinically significant.”  Any clinically significant value should be 
repeated as necessary and followed until resolution. 
6.14 Sample Collection for Pharmacokinetic Analysis 
Blood samples for PK analysis of lefamulin and its main metabolite, BC-8041, will be 
collected in association with the first dose of study drug on Day 1 and Day 4 (see Table 5).   

Nabriva Therapeutics AG 
Clinical Protocol NAB-BC-3781-3102 
 
 
V3.0:  17-Mar-2016 
Page 64 of 102 
Confidential Information 
If PK sampling for Inpatients on Day 4 is not feasible, it can be done relative to the first dose 
on Day 5.  For Outpatients, PK sampling will be done during the 96 ± 24 hours post 1st dose 
visit.  Subjects will be instructed to not take their first dose of study drug at home that day, 
rather to bring all blister packs (used and unused) to the study site.  Following collection of 
the pre-dose blood sample, subjects will take their dose of study drug under supervision of 
study personnel, and subsequent PK blood samples will be collected.   
Table 5. 
Sample Collection Time Points for the Determination of Lefamulin 
Plasma Concentrations following Oral Administration 
PK Sample Time Point 
Day 1 and Day 4 or 96 ± 24 hours post 1st dose a,b 
Within 1 h prior to the first dose of study drug 
X 
1-2 h after the first dose of study drug 
X 
3-4 h after the first dose of study drug 
X 
8-9 h after the first dose of study drug c 
X 
a: 
Day 1 [all subjects] and Day 4 [Inpatients] or 96  ±  24 hours post first dose [Outpatients] 
b: 
If Day 4 PK sampling for Inpatients is not feasible, it can be done relative to the morning dose on Day 5. 
c: 
The 8-9 h sample is required for inpatients.  The 8-9 h sample is optional for outpatients; however, it 
should be obtained if logistically feasible. 
 
NOTE:  It is essential to record the exact time of dosing on those days when PK samples are 
obtained (see Section 5.7 – Adherence).  Documentation of the exact blood sampling time 
points for population PK analysis is also essential. 
6.14.1 
Sample Collection Methodology  
Blood samples for PK analysis will be collected into tubes containing K3EDTA, immediately 
chilled on crushed ice, and then centrifuged to separate plasma.  Promptly following 
centrifugation, plasma specimens (2 aliquots: 1 for bioanalysis and 1 for backup) will be 
immediately deep frozen and stored at -20 ºC or cooler until transported to the central 
laboratory.  The total time period from blood withdrawal to storage of plasma at -20 ºC 
should not exceed 60 minutes   
Additional information and instructions for blood sample collection is provided in the 
Laboratory Manual. 
6.14.2 
Assay Methodology  
Plasma samples from subjects who received lefamulin will be analyzed for the concentration 
of lefamulin and its main metabolite, BC-8041, using a validated liquid chromatography-
tandem mass spectrometry method at the bioanalytical laboratory A&M GmbH (Bergheim, 
Germany).  Samples from subjects who did not receive lefamulin (i.e., received the 
comparator) will not be analyzed.  Scientists at the bioanalytical laboratory will be unblinded 
before bioanalysis. 

Nabriva Therapeutics AG 
Clinical Protocol NAB-BC-3781-3102 
 
 
V3.0:  17-Mar-2016 
Page 65 of 102 
Confidential Information 
6.15 Microbiological Assessment 
The following microbiological assessments will be performed at the time points described in 
Table 1.  Details regarding storage of samples and shipment to the central laboratory can be 
found in the Laboratory Manual. 
6.15.1 
Sputum Samples 
• A sputum sample will be taken at Screening for Gram’s staining, culture and 
susceptibility testing at the local/regional laboratory.  If a subject is unable to produce an 
adequate (> 25 polymorphonuclear (PMN) cells AND < 10 squamous epithelial cells per 
LPF) sputum sample at Screening, a repeat specimen should be obtained, if possible, 
within 24 hours after the first dose of study drug. Gram’s stain and culture results from 
the local/regional laboratory will be recorded in the eCRF. 
• If possible, subjects who are discontinued from study drug due to clinical failure should 
have repeat cultures collected for microbiologic culture prior to switching to alternate 
appropriate therapy. 
• Sputum samples will only be taken at subsequent visits when clinically indicated.  
• All organisms isolated from sputum samples which are not considered contaminants will 
be sent to the central laboratory for confirmatory identification and susceptibility testing.  
The following organisms, if isolated, will always be sent to the central laboratory for 
confirmatory identification and susceptibility testing: S. pneumoniae, S. aureus, 
S. pyogenes, Haemophilus spp., M. catarrhalis, L. pneumophila, C. pneumoniae, and 
M. pneumoniae. Further details regarding organisms which should be sent to the central 
microbiology laboratory, including a list of organisms which if isolated will be classified 
as contaminants, can be found in the Laboratory Manual. 
• Gram’s stain slides will be sent to the central laboratory for a confirmatory reading.  The 
stained slide read by the local/regional laboratory as well as an unstained slide will be 
sent to the central laboratory. 
• A portion of each Screening sputum sample taken will be frozen until shipment to the 
central laboratory.  Frozen samples will be analyzed by the central microbiological 
laboratory using real-time quantitative PCR for common CABP pathogens.  Additionally, 
for subjects who have a positive urinary antigen test for Legionella spp. the frozen 
sputum will be utilized for L. pneumophila isolation and susceptibility testing.   
6.15.2 
Bronchoalveolar Lavage Samples (BAL)  
A BAL sample is not required per the protocol and will be collected only if clinically 
indicated per the Investigator, and sent to the local/regional laboratory for Gram’s staining, 
culture and susceptibility testing.  However, if the subject undergoes a repeat bronchoscopy 
as clinically warranted per the investigator, a repeat BAL sample should be sent for Gram’s 
staining and culture.  All organisms isolated from BAL samples, which are not considered 
contaminants, will be sent to the central laboratory for confirmatory identification and 

Nabriva Therapeutics AG 
Clinical Protocol NAB-BC-3781-3102 
 
 
V3.0:  17-Mar-2016 
Page 66 of 102 
Confidential Information 
susceptibility testing.  Culture results from the local/regional laboratory will be recorded in 
the eCRF. 
6.15.3 
Pleural Fluid Samples 
A pleural fluid sample is not required per the protocol, and will be collected only if clinically 
indicated per the Investigator and sent to the local/regional laboratory for Gram’s staining, 
culture and susceptibility testing.  However, if the subject undergoes a repeat thoracentesis as 
clinically warranted per the Investigator, a repeat pleural fluid sample should be sent for 
Gram’s staining and culture. If possible, pleural fluid samples should be incubated in blood 
culture bottles for optimal pathogen recovery.  All organisms isolated from pleural fluid 
samples which are not considered contaminants will be sent to the central laboratory for 
confirmatory identification and susceptibility testing.  Culture results from the local/regional 
laboratory will be recorded in the eCRF. 
6.15.4 
Blood Cultures 
Two sets of blood cultures via venipuncture will be obtained at Screening and sent to the 
local/regional laboratory.  Repeat blood samples for culture should be taken as clinically 
indicated during the study.  Blood cultures should be repeated after a positive result until 
sterilization is documented.  All organisms isolated from blood cultures which are not 
considered contaminants will be sent to the central laboratory for confirmatory identification 
and susceptibility testing.  Subjects who have confirmed bacteremia should have blood 
samples collected for microbiologic culture prior to switch to alternate appropriate therapy.  
Subjects who have confirmed S. aureus bacteremia must be withdrawn from the study.  
Culture results from the local/regional laboratory will be recorded in the eCRF. 
6.15.5 
Serological Testing 
Blood samples will be collected at Screening and LFU, and sent frozen to the central 
laboratory for serologic tests for M. pneumoniae, C. pneumoniae, and L. pneumophila.   
6.15.6 
Urine Antigen Test 
A urine sample will be taken at Screening and tested at the clinical site for L. pneumophila 
and S. pneumoniae antigen.  Results will be recorded in the eCRF. Clinical sites that are 
unable to perform urinary antigen testing will send urine to the central laboratory for testing.  
Subjects who have urinary antigen test positive for L. pneumophila at Screening, or sites that 
are sending urine to the central laboratory for urinary antigen testing, will have a portion of 
the sputum sample collected at Screening sent to the central laboratory for L. pneumophila 
testing as described above (Section 6.15.1). 
6.15.7 
Oropharyngeal Specimen 
An oropharyngeal specimen (2 swabs) will be obtained at Screening and sent to the central 
laboratory/specialty laboratory for M. pneumoniae culture, susceptibility testing, as well as 
identification by PCR.  Oropharyngeal specimens must be frozen until shipment to the 
central laboratory.   

Nabriva Therapeutics AG 
Clinical Protocol NAB-BC-3781-3102 
 
 
V3.0:  17-Mar-2016 
Page 67 of 102 
Confidential Information 
6.15.8 
Nasopharyngeal Specimen 
A nasopharyngeal specimen (1 swab) will be obtained at Screening and sent to the central 
laboratory/specialty laboratory for S. pneumoniae culture, susceptibility testing, as well as 
identification by PCR.  Culture, susceptibility testing, as well as identification by PCR may 
also be performed for H. influenzae.  Nasopharyngeal specimens must be frozen until 
shipment to the central laboratory.   
6.16 Health Utilization and Patient Reported Outcome 
Exploratory evaluation of a variety of health utilization variables (e.g., length of hospital 
stay, duration of antibiotic therapy, discharge status, discharge destination) as well as a PRO 
instrument (SF-12) will be administered.  Details for this exploratory analysis will be 
presented in a separate SAP and results will be presented in a stand-alone clinical study 
report. 
6.17 Food and Beverage Restrictions  
Subjects should refrain from drinking alcohol throughout study drug administration period. 
In addition, as discussed in Section 5.4, study drug should be administered at least 1 hour 
before a meal or 2 hours after a meal.  However, in the event that a subject has taken any of 
the following − antacids containing aluminum, products containing iron, or multivitamins 
containing zinc − study drug should be administered 2 hours before or 4 hours after 
consuming any of these medications.   
6.18 Discontinuation from Treatment or Study 
Subjects are free to withdraw from the study at any time for any reason.  Subjects may be 
withdrawn from study at the discretion of the Principal Investigator or Sub-Investigator at 
any time.  Once a subject has been withdrawn from the study they may not be re-entered.  
Subjects who withdraw or who are withdrawn from the study will not be replaced.  If a 
subject is discontinued from treatment or from the study, the reason for discontinuation will 
be collected in the eCRF. 
6.18.1 
Discontinuation from Treatment 
A subject may be discontinued prematurely from study drug treatment for the following 
reasons: 
• Lack of efficacy (i.e., requirement for additional non-study antibacterial therapy to treat 
the current episode of CABP) 
• Adverse event 
• Withdrawal by subject [specify reason in the eCRF] 
• Lost to follow-up 

Nabriva Therapeutics AG 
Clinical Protocol NAB-BC-3781-3102 
 
 
V3.0:  17-Mar-2016 
Page 68 of 102 
Confidential Information 
• Physician decision (i.e., Investigator decision based on protocol violation, assessment that 
it is not in the subject’s best interest to continue, or other reason) [specify reason in the 
eCRF] 
• Sponsor decision [specify reason in the eCRF] 
If a subject is prematurely withdrawn from study drug treatment, the Investigator should 
make every effort to retain the subject in the study and perform all procedures scheduled for 
the EOT, TOC, and LFU visits.  Any subject withdrawn from treatment due to an AE, SAE, 
or clinically significant abnormal laboratory test value will be evaluated by the Investigator, 
or a monitoring physician, and will be treated and/or followed up until the symptoms or 
values have either resolved or are assessed as stable by the Investigator.  
6.18.2 
Discontinuation from Study 
A subject may be discontinued prematurely from the study for the following reasons: 
• Withdrawal by subject [specify reason in the eCRF] 
• Lost to follow-up 
• Death 
• Physician decision (i.e., assessment that it is not in the subject’s best interest to continue, 
or other reason) [specify reason in the eCRF] 
• Sponsor decision [specify reason in the eCRF] 
Every attempt will be made to contact subjects who withdraw from the study in order to 
determine their vital status (alive or dead) at Day 28.   
6.18.3 Individual Stopping Criteria 
Subjects will be withdrawn from the study drug treatment for any of the following reasons: 
• The subject demonstrates an average QTcF value > 500 ms (mean of 3 ECG’s at any time 
point) as assessed locally by the Investigator.  Such subjects should be observed until the 
ECG normalizes with repeat ECG’s taken at the discretion of the investigator. 
• The subject demonstrates an average QTcF value > 480 ms with a concurrent increase in 
average QTcF value of > 60 ms (mean of 3 post-dose ECGs compared to mean pre-dose 
ECGs taken on that day) as assessed locally by the Investigator.   
• The subject has confirmed S. aureus bacteremia.   
If a subject is prematurely withdrawn from study treatment, the Investigator should make 
every effort to retain the subject in the study and to perform all procedures scheduled for the 
EOT, TOC, and LFU visits.  Any subject withdrawn from treatment due to an AE, SAE, or 
clinically significant abnormal laboratory test value will be evaluated by the Investigator, or a 

Nabriva Therapeutics AG 
Clinical Protocol NAB-BC-3781-3102 
 
 
V3.0:  17-Mar-2016 
Page 69 of 102 
Confidential Information 
monitoring physician, and will be treated and/or followed up until the symptoms or values 
have either resolved or are assessed as stable by the Investigator.  
6.18.4 
Lost to Follow-up 
Every reasonable attempt should be made to retain subjects in the study. If a subject does not 
report to the study site for a scheduled visit, study personnel will make 4 contact attempts:  3 
telephone contact attempts and, if these are unsuccessful, a certified letter will be sent to the 
subject.  The subject will be considered lost to follow-up if (1) upon receipt of delivery 
confirmation of the certified letter the subject does not contact the site or (2) the certified 
letter is returned as undeliverable.  Every attempt will be made to contact subjects who 
withdraw from the study in order to determine their status (alive or dead) at Day 28. 
7 
ADVERSE EVENTS 
An adverse event (AE) is any untoward medical occurrence in a subject or clinical 
investigation subject administered a pharmaceutical product that does not necessarily have a 
causal relationship with this treatment.  An AE can therefore be any unfavorable and 
unintended sign (including an abnormal laboratory finding), symptom, or disease temporally 
associated with the use of an investigational product, whether or not related to the 
investigational medicinal product.  
Any pre-existing conditions or signs and/or symptoms present in a subject prior to the start of 
the study (i.e., before informed consent) should be recorded as medical/surgical history.  Any 
medical occurrences which are new or worsened from the time of informed consent and up to 
and including the final visit must be reported as AEs or SAEs.  All AEs and SAEs must be 
recorded irrespective of whether they are considered drug related.  NOTE:  lack of 
efficacy/clinical failure does not have to be recorded as an AE unless it is an SAE. 
Subjects will be monitored throughout the study for adverse reactions to the study 
medications and/or procedures at each study visit.  Questions will be posed in a non-leading 
manner so as not to bias the response.  In addition to questioning at specific time points, 
subjects will be encouraged to spontaneously report any AEs.  Any subject with an AE, SAE 
or clinically significant abnormal laboratory test value will be evaluated by the Investigator, 
or a monitoring physician, and will be treated and/or followed up until the symptoms or 
values have resolved or are assessed as stable by the by the Investigator.  A physician, either 
at the Investigative site or at a nearby hospital emergency room, will administer treatment of 
any SAEs.  Where appropriate, medical tests and examinations may be performed to ensure 
that an AE has fully resolved.  
Adverse events will be monitored throughout the study from the time a subject is consented 
through the TOC visit; SAEs are to be collected from the time of consent through the LFU 
visit.  Study personnel will monitor AEs for subjects who are Outpatients in conjunction with 
daily telephone contacts for CABP signs/symptoms as well as at all site visits (see Table 1).  
Study personnel will follow unresolved AEs and SAEs present at LFU until resolution or 
stabilization.    

Nabriva Therapeutics AG 
Clinical Protocol NAB-BC-3781-3102 
 
 
V3.0:  17-Mar-2016 
Page 70 of 102 
Confidential Information 
Whenever possible, a specific disease or syndrome rather than individual associated signs 
and symptoms should be identified by the Investigator and recorded on the subject's eCRF.  
However, if an observed or reported sign or symptom is not considered a component of a 
specific disease or syndrome by the Investigator, it should be recorded as a separate AE on 
the subject's eCRF.  
Each AE or SAE reported will be assessed for intensity and the date and time of onset (if 
available), time relationship to dosing, duration, and outcome of each event will be noted. 
Laboratory abnormalities are not considered AEs unless they are associated with clinical 
signs and symptoms or require medical intervention.  Clinically significant abnormal clinical 
laboratory findings or other abnormal assessments that are associated with the disease being 
studied, unless judged by the Investigator as more severe than expected for the subject’s 
condition, or that are present or detected at the start of the study and do not worsen, will not 
be reported as AEs or SAEs. 
The Investigator will exercise medical and scientific judgment in deciding whether an 
abnormal clinical laboratory finding or other abnormal assessment is clinically significant.  
7.1 Assessment of Severity (Intensity) 
The following definitions for rating severity (intensity) will be used: 
Mild:  
A type of AE that is usually transient and may require only minimal 
treatment or therapeutic intervention. The event does not generally interfere 
with usual activities of daily living 
Moderate:  
A type of AE that is usually alleviated with specific therapeutic intervention. 
The event interferes with usual activities of daily living, causing discomfort 
but the subject is still able to function 
Severe: 
The type of AE that interrupts usual activities of daily living, or significantly 
affects clinical status, or may require intensive therapeutic intervention. 
7.2 Assessment of Relationship to Study Drug 
The Investigator will use his/her clinical judgment to explain each adverse event and 
determine its relationship, if any, to study drug treatment.  Alternative causes, such as natural 
history of the underlying diseases, concomitant therapy, other risk factors, and the temporal 
relationship of the event to the study drug will be considered and investigated.  The 
Investigator will also consult the Investigator’s Brochure in the determination of his/her 
assessment.  Causality should be assessed using the following categories: 
Not related  
The event could readily be explained by factors not involving the study 
drug and a temporal relationship with the study drug did not exist.  
Possibly Related  
There was some temporal relationship between the event and the 
administration of the study drug and the event was unlikely to be 
explained by the subject’s medical condition or other therapies. 

Nabriva Therapeutics AG 
Clinical Protocol NAB-BC-3781-3102 
 
 
V3.0:  17-Mar-2016 
Page 71 of 102 
Confidential Information 
Probably Related  
The temporal relationship between the event and the administration of 
the study drug was suggestive, and the event was less likely to be 
explained by the subject’s medical condition or other therapies.  
Definitely Related  The 
event 
followed 
a 
reasonable 
temporal 
sequence 
from 
administration of the study drug, followed a known or suspected 
response pattern to the study drug, was confirmed by improvement 
upon stopping the study drug (dechallenge) and reappeared upon 
repeated exposure (rechallenge).  (NOTE:  this was not to be construed 
as requiring re-exposure of the subject, however, a category of 
definitely related could only be used when recurrence was observed.). 
7.3 Serious Adverse Events 
An SAE is any untoward medical occurrence that: 
• Results in death. 
• Is life-threatening. NOTE: The term ‘life threatening’ in the definition of “serious” refers 
to an event in which the subject was at risk of death at the time of the event; it does not 
refer to an event which hypothetically might have caused death if it was more severe.  
• Results in persistent or significant disability/incapacity. 
• Requires in subject hospitalization or prolongation of existing hospitalization. 
NOTE: Hospitalizations, which are the result of elective or previously scheduled surgery 
for pre-existing conditions, which have not worsened after entry into the study, should 
not be classified as SAEs. For example, admission for a previously scheduled ventral 
hernia repair would not be classified as an SAE; however, complication(s) resulting from 
a hospitalization for an elective or previously scheduled surgery that meet(s) serious 
criteria must be reported as SAE(s). 
• Is a congenital anomaly/birth defect. 
• Is an important medical event. 
NOTE:  Medical or scientific judgment should be exercised in deciding whether reporting 
is appropriate in other situations, such as important medical events that may not be 
immediately life threatening or result in death or hospitalization but may jeopardize the 
subject or may require medical or surgical intervention to prevent one of the other 
outcomes listed in the above definition.  These should also be considered serious.  
Examples of such events are invasive or malignant cancers, intensive treatment in an 
emergency room or at home for allergic bronchospasm, blood dyscrasias, or convulsions 
that do not result in hospitalization, or development of drug dependency or drug abuse. 
 
All SAEs will be collected from the time of informed consent until 30 days after the last 
study treatment regardless of study drug relationship, and must be reported to Nabriva 
Therapeutics AG or their representative (Covance Pharmacovigilance & Drug Safety 
Services [PV & DSS]) within 24 hours of knowledge of the event (this refers to any AE that 
meets one or more of the aforementioned serious criteria). 

Nabriva Therapeutics AG 
Clinical Protocol NAB-BC-3781-3102 
 
 
V3.0:  17-Mar-2016 
Page 72 of 102 
Confidential Information 
Safety Contact Information (24 hours/day): 
 
Location 
Phone 
Fax 
United States 
+1-888-724-4908 
1-888-887-8097 
Latin America 
+55-11-3750-3900 
+0800-892-1513 
Europe 
+44-1628-548-171 
+44-1628-540028 
Asia Pacific 
+61-2-8879-2000 
+61-2-9888-8322 
 
When the SAE form is completed in EDC, Nabriva Therapeutics AG or their representative 
(Covance PV & DSS) will be notified electronically and will retrieve the form.  If the event 
meets serious criteria and it is not possible to access the system, sites must email or fax the 
completed paper SAE report form to Covance PV&DSS at drugsafety@covance.com.  The 
emailed report should include all available information requested on the SAE form.  The 
SAE form will collect data surrounding the event, e.g., the nature of the symptom(s), time of 
onset in relation to initiation of therapy, duration, intensity, and whether or not therapy was 
interrupted or discontinued.  The Investigator’s assessment of the probable cause of the event 
will also be included.  In addition, relevant medical history, concomitant medications, 
laboratory and diagnostic reports, and procedures, as well as all pertinent medical 
information related to the event, will also be collected. 
Covance PV&DSS will forward SAE queries directly to the Investigator requesting 
incomplete or missing information.  It is the Investigator’s responsibility to be diligent in 
providing this information back to the Covance PV&DSS as soon as it is available.  Initial 
reports of SAEs should never be left on telephone voicemails.  
There may be situations when an SAE has occurred and the Investigator has minimal 
information to include in the initial report to Nabriva Therapeutics AG, or their 
representative.  However, it is very important that the Investigator always makes an 
assessment of causality for every event prior to transmission of the SAE report form to 
Nabriva Therapeutics AG, or their representative.  The Investigator may change his/her 
opinion of causality in light of follow-up information, amending the SAE report form 
accordingly.  The causality assessment is one of the criteria used when determining 
regulatory reporting requirements. 
The Investigator will provide the assessment of causality as per instructions on the SAE form 
in the subject's eCRF.  SAEs that are determined by the Investigator to be related to the study 
drug must be reported even if more than 30 days after the last administration of study drug. 
The sponsor will not routinely unblind the therapy assignment for an individual subject in the 
event of a serious adverse event.  However, unblinding of an individual subject may occur if 
this information is requested by the Investigator, if the Sponsor determines that the 
information is necessary to adequately assess safety, or if this information is required for 
reporting to local regulatory authorities (see Section 5.6). 

Nabriva Therapeutics AG 
Clinical Protocol NAB-BC-3781-3102 
 
 
V3.0:  17-Mar-2016 
Page 73 of 102 
Confidential Information 
All serious adverse events and suspected unexpected serious adverse events (SUSARs) will 
be reported by the sponsor to the relevant competent authorities in accordance with the 
European Directive 2001/20/EC, as applicable. 
7.4 Symptoms of the Disease Under Study 
In this study, clinical signs and symptoms of pneumonia which are assessed daily per 
protocol (i.e., dyspnea, cough, sputum production, and chest pain) will not be reported as 
adverse events unless they meet the definition of a serious adverse event.  
7.5 Other Reportable Events 
Certain events that occur should be reported to the Sponsor as Other Reportable Events.  
These include the following: 
• Potential Hy’s Law (PHL) 
- 
The investigator is responsible for prompt reporting of any patients who has had both 
(1) AST or ALT > 3 x ULN and (2) total bilirubin > 2 x ULN at any point in the 
study (i.e., meets criteria for Potential Hy’s Law). The investigator must complete the 
Hy’s Law eCRF.  Liver laboratory results should be followed locally every several 
days until resolution or stabilization of the laboratory abnormalities and reported 
using an unscheduled laboratory eCRF.  If subsequent to the initial report of PHL, the 
investigator determines that the case meets serious criteria, it should be reported as an 
SAE using standard reporting procedures. 
• Pregnancy exposure (subject becomes pregnant while taking study drug) 
- 
Subjects who are pregnant at Screening are not permitted to take part in this study, 
however, Nabriva Therapeutics AG or their representative must be notified of any 
subjects that become pregnant while participating in this study (or the partner of a 
male subject).  Although pregnancy is not technically an AE, all pregnancies must be 
followed to conclusion to determine their outcome.  This information is important for 
both drug safety and public health concerns.  It is the responsibility of the Investigator 
or designee to report any pregnancy in a subject that occurs during this study to 
Nabriva Therapeutics AG or their representative.  
• Lactation exposure (subject was taking study drug while nursing an infant) 
• Accidental exposure (someone other than the study subject was exposed to study drug) 
• Overdose (subject received more than the prescribed dose of study drug within a given 
timeframe) 
• Other medication errors that potentially place subjects at a greater risk of harm than was 
previously known or recognized (e.g., study drug was administered by an incorrect 
route). 
 

Nabriva Therapeutics AG 
Clinical Protocol NAB-BC-3781-3102 
 
 
V3.0:  17-Mar-2016 
Page 74 of 102 
Confidential Information 
8 
DRUG SUPPLIES 
8.1 Lefamulin (BC-3781) 
The active substance being investigated in this study is lefamulin (BC-3781), present in the 
drug product as the acetate salt (BC-3781.Ac).  Physicochemical properties can be found in 
the Lefamulin Investigator’s Brochure. 
Oral lefamulin is supplied by the Sponsor as 600 mg yellow oval film coated immediate-
release tablets.  Details of the composition are provided in the Lefamulin Investigator’s 
Brochure. 
8.2 Moxifloxacin 
The oral dose of moxifloxacin is provided by the Sponsor as an over-encapsulated film 
coated tablet containing 400 mg as hydrochloride.  
Additional details regarding moxifloxacin are found in the product monograph.  
8.3 Placebo 
The following oral placebo tablets will be supplied by the Sponsor: lefamulin placebo tablet 
and moxifloxacin placebo capsule.  
Further details may be found in the Study Pharmacy Manual. 
8.3.1 
Packaging and Labeling 
Study drugs will be packaged and labeled in accordance with the applicable regulatory 
authority requirements. 
8.3.2 
Storage of Study Drugs 
Access to all study drugs at the site must be restricted to designated study personnel 
throughout the study. 
Oral study medication will be supplied in blister packs.  Two different blister packs will be 
provided: 
• Lefamulin tablets and moxifloxacin placebo capsules. 
• Over-encapsulated moxifloxacin tablets and lefamulin placebo tablets 
The two blister packs must be stored at controlled room temperature (15 to 25 °C). 
8.3.3 
Product Accountability 
The Investigator is responsible for study medication accountability, reconciliation, and record 
maintenance.  In accordance with all applicable regulatory requirements, the Investigator or 

Nabriva Therapeutics AG 
Clinical Protocol NAB-BC-3781-3102 
 
 
V3.0:  17-Mar-2016 
Page 75 of 102 
Confidential Information 
designated study personnel must maintain study drug accountability records throughout the 
course of the study.  This person(s) will document the amount of study drug received from 
the supplier, the amounts dispensed to subjects as well as lot numbers and expiration / retest 
date of study medications. 
At the conclusion of the study, any unused study drug will be returned to either a 
Sponsor-designated recipient or destroyed at the site after discussion with the Sponsor.  If no 
supplies remain, this will be recorded in the drug accountability section of the final 
monitoring report. 
9 
STATISTICAL ANALYSIS 
Inferential statistical analyses of the primary and secondary outcomes will be conducted as 
outlined below.  Descriptive statistics, including the numbers and percentages for categorical 
variables, and the numbers, means, standard deviations, medians, minimums, and maximums 
for continuous variables will be provided.  Additional statistical analyses, other than those 
described in this section, may be performed if deemed appropriate.  A description of the 
statistical analysis performed on the study data will be outlined in the SAP. 
As a consequence of differing regulatory requirements for the choice of primary efficacy 
analysis variable and statistical analyses of this study, 2 separate regional comprehensive 
SAPs will be prepared (FDA and EMA) and finalized before database lock and analysis of 
the data.   
Exploratory evaluation of a variety of health utilization variables (e.g., length of hospital 
stay, duration of antibiotic therapy, discharge status, discharge destination) as well as a PRO 
instrument will be performed. Details for this exploratory analysis will be presented in a 
separate SAP and results will be presented in a stand-alone clinical study report. 
9.1 Treatment Comparison of Interest 
All comparisons will be for lefamulin versus comparator therapy (moxifloxacin). 
9.2 Sample Size Determination 
A total of 738 subjects will be randomized in a ratio of 1:1 (lefamulin:moxifloxacin) 
resulting in 369 subjects in the lefamulin arm and 369 in the moxifloxacin arm in this study.  
The total number of subjects included in this study is sufficient to achieve the primary and 
secondary study objectives based on statistical considerations. 
Retrospective analyses of clinical study data for patients with CABP of varying severity as 
well as 2 recent clinical trials in CABP indicate the point estimates for an ECR responder at 
Days 3-5 range from 72% to 81% (FDA, 2011; Barrera et al., 2016; Cempra, 2015; Oldach et 
al., 2015).  Thus, it is reasonable to assume that in a prospective study of subjects with 
CABP, the proportion of subjects who are responders for ECR at 96 ± 24 hours post first dose 
of study drug will be approximately 79%.   

Nabriva Therapeutics AG 
Clinical Protocol NAB-BC-3781-3102 
 
 
V3.0:  17-Mar-2016 
Page 76 of 102 
Confidential Information 
The primary efficacy analysis variables used for NI analyses for the Marketing Authorization 
Application (MAA) to the EMA will be the proportion of subjects with an IACR of Success 
at TOC in the mITT and CE-TOC Analysis Sets.  In recent clinical studies, IACR success 
rates at the TOC Visit in the CE Analysis Set ranged from 77% to 93% (Cempra, 2015) and 
in the ITT Analysis Set ranged from 85% to 89% depending on the antibiotics under study 
and the severity of the CABP.  Based on these data, an 85% IACR success rate in the CE-
TOC Analysis Set was chosen for determination of the sample size.  The success rate is 
expected to be about 5% lower in the mITT Analysis set.  It is expected that <1% of subjects 
will be excluded from the mITT Analysis Set and thus, the sample size determination 
assumes the same number of subjects in the ITT and mITT Analysis Sets. 
Utilizing an anticipated ECR responder rate of 79% in the ITT Analysis Set, a 1:1 
randomization ratio, a two-sided alpha of 0.025, and a continuity corrected Z-test with 
unpooled variance, a sample size of 738 subjects (369 subjects in the lefamulin group and 
369 in the moxifloxacin group) provides 90% power to establish the NI of lefamulin to 
moxifloxacin for ECR using a NI margin of 10.0% at the ECA.  Assuming an IACR success 
of 80% and 85% in the mITT and CE-TOC Analysis Sets, respectively, and a clinical 
evaluability rate of 80%, there is 91% power for demonstration of NI for IACR at the TOC 
Visit using a 10% NI margin. 
The calculated power in each analysis set for the primary and secondary outcomes is 
provided in Table 6 below. 
Table 6. 
Power Calculations for the Primary and Secondary Efficacy 
Outcomes 
 
Primary Outcome (FDA) 
(ECR 96 ± 24 hours After the First 
Dose of Study Drug) 
Secondary Outcome  
(Investigator’s Assessment of Clinical Response at 
TOC- Primary for EMA) 
Analysis Set 
ITT 
mITT 
CE-TOC 
NI Margin 
10% 
10% 
10% 
N 
738 (369:369) 
738 
590 
Outcome Rate 
79% 
80% 
85% 
Evaluability Rate 
NA 
NA 
80% 
Power 
90% 
91 % 
91% 
CE = clinically evaluable; ITT = intent to treat; mITT = modified ITT; TOC = test of cure 
 
9.3 Analysis Populations 
9.3.1 
Intent-to-Treat Analysis Set (ITT) 
The ITT Analysis Set will consist of all randomized subjects regardless of whether or not the 
subject received study drug. A subject is considered randomized when an IRT-generated 
randomization number has been assigned. 

Nabriva Therapeutics AG 
Clinical Protocol NAB-BC-3781-3102 
 
 
V3.0:  17-Mar-2016 
Page 77 of 102 
Confidential Information 
9.3.2 
Modified Intent-to-Treat Analysis Set (mITT) 
The mITT Analysis Set will consist of all randomized subjects who receive any amount of 
study drug.  Subjects are analyzed based on the randomized (i.e., assigned) treatment group. 
9.3.3 
Safety Analysis Set 
The Safety Analysis Set will consist of all randomized subjects who receive any amount of 
study drug.  Subjects are analyzed based on the study drug actually received. All safety 
analyses will be conducted in this population.  
9.3.4 
Microbiological Intent-to-Treat Analysis Set (microITT) 
The microITT Analysis Set will consist of all subjects in the ITT Analysis Set who have at 
least 1 baseline “typical” bacterial pathogen known to cause CABP, Legionella pneumophila 
from an appropriate microbiological specimen, or who have CABP caused by Mycoplasma 
pneumoniae or Chlamydophila pneumoniae. 
9.3.5 
Clinically Evaluable Analysis Set  
The CE Analysis Sets (CE-EOT, CE-TOC and CE-LFU Analysis Sets) will be a subset of the 
ITT Analysis Set that will include subjects who meet the criteria for CABP described in 
Inclusion Criteria Nos. 3-7, and who received at least the pre-specified minimal amount of 
the intended dose of study drug and duration of treatment, do not have an indeterminate 
response based on the IACR (at EOT for the CE-EOT Analysis Set, at TOC for the CE-TOC 
Analysis Set and at LFU for the CE-LFU Analysis Set), did not receive concomitant 
antibacterial therapy that is potentially effective against CABP pathogens (except in the case 
of clinical failure) from the first dose of study drug through the EOT Visit (CE-EOT 
Analysis Set),  through the TOC Visit (CE-TOC Analysis Set) and through the LFU Visit 
(CE-LFU Analysis Set), and for whom there are no other confounding factors that interfere 
with the assessment of the outcome.  
9.3.6 
Microbiologically Evaluable Analysis Set 
The ME Analysis Sets (ME-EOT, ME-TOC and ME-LFU) will include all subjects who 
meet the criteria for inclusion in both the microITT and CE-EOT (ME-EOT) Analysis Sets, 
the CE-TOC (ME-TOC) Analysis Set, or the CE-LFU (ME-LFU) Analysis Set. 
9.3.7 
Pharmacokinetic Analysis Set 
All subjects who receive any amount of study drug will be included in the formal analysis of 
PK parameters providing they have at least 1 evaluable PK sample.   

Nabriva Therapeutics AG 
Clinical Protocol NAB-BC-3781-3102 
 
 
V3.0:  17-Mar-2016 
Page 78 of 102 
Confidential Information 
9.4 Criteria for Evaluation 
9.4.1 
Primary Efficacy Analysis Variable 
The primary efficacy variable (FDA) is the proportion of subjects in the ITT Analysis Set 
with an ECR of Responder at 96 ± 24 hours post first dose. 
Subjects will be defined as an ECR of Responder if the following 4 criteria are met: 
• Alive 
• Improvement in at least 2 of the 4 cardinal symptoms of CABP (Section 6.11), the 
subject presented with at Baseline. Improvement is defined as a decrease by at least 1 
level of severity. 
• No worsening of any of the 4 cardinal symptoms of CABP. Worsening is defined as an 
increase from Baseline by at least 1 level of severity of any symptom. 
• Did not receive a concomitant antibiotic for the treatment of CABP. 
The primary efficacy variable for the EMA (and secondary efficacy variable for the FDA) is 
the proportion of subjects with an IACR of Success at TOC in the mITT and CE-TOC 
Analysis Sets (see Section 6.12).  An IACR of Success is defined as a subject whose clinical 
signs and symptoms have resolved or improved such that no additional antibacterial therapy 
is administered for the treatment of the current episode of CABP. Subjects who have an 
IACR of Failure at EOT will not have an IACR assessed at TOC and will be considered to 
have an IACR of Failure at TOC. 
9.4.2 
Secondary Efficacy Analysis Variables 
9.4.2.1 
Clinical Outcome 
The Investigator’s Assessment of Clinical Response will be evaluated in the microITT and 
ME-TOC Analysis Sets at TOC as described in Section 6.12.  ECR will be evaluated in the 
microITT Analysis Set. All-cause mortality will be evaluated in the ITT Analysis Set. 
9.4.2.2 
Microbiological Assessment 
The By-Pathogen Microbiological Response will be assessed in the micro-ITT and ME 
Analysis Sets for each causative organism using the categories for outcome as follows.  
• Success includes: 
− Eradication:  the baseline causative pathogen was absent from repeat culture(s). 
− Presumed eradication:  the IACR was Success, and culture was not repeated.  
• Failure includes: 
− Persistence:  the baseline causative pathogen was isolated in repeat culture(s).  
− Presumed persistence:  the IACR was Failure and a culture was not repeated. 

Nabriva Therapeutics AG 
Clinical Protocol NAB-BC-3781-3102 
 
 
V3.0:  17-Mar-2016 
Page 79 of 102 
Confidential Information 
• Indeterminate:  
- 
The IACR was Indeterminate, and culture was not repeated. 
9.4.3 
Safety Analysis Variables 
Safety will be assessed by monitoring vital signs, ECG measurements, clinical laboratory 
parameters, and AEs.  
9.4.4 
Pharmacokinetic Analysis Variables 
Population PK modeling will be performed to determine the model-predicted plasma 
concentration time curves of lefamulin for each subject.  Calculated PK will enable 
descriptive statistical analysis of PK variables such as the maximum observed drug 
concentration (Cmax) and area under the concentration-time curve (AUC) for lefamulin and its 
main metabolite, BC-8041.  Individual AUC values from Day 1 and Day 4 [i.e., 96  ±  24 
hours post first dose] (collected pre-dose, 1-2 h post dose and 3-4 h post dose, and 8-9 h post 
dose (8-9 h post dose is required for inpatients; optional for outpatients) will be used for the 
PK/PD analysis.  The population PK analysis as well as a PK/PD analysis will be reported 
separately. 
9.4.5 
Other Variables 
The Investigator’s Assessment of Clinical Response at EOT and at LFU will be evaluated in 
the mITT and CE Analysis Sets. 
The By-Subject Microbiological Response will be programmatically determined at TOC for 
each subject using the By-Pathogen Microbiological Response for each baseline causative 
pathogen.  For a subject to have a By-Subject Microbiological Response of Success, the 
response for each baseline pathogen must be Success (i.e., Eradication or Presumed 
Eradication).  If the response for any Baseline pathogen is Failure (i.e., Persistence or 
Presumed Persistence), the subject will be considered to have a By-Subject Microbiological 
Response of Failure.  A By-Subject Microbiological Response of Indeterminate will be 
assigned if all baseline pathogens have a Microbiological Response of Indeterminate. 
New bacteria isolated from respiratory or blood culture will be assessed separately from the 
outcomes listed above as follows: 
• Superinfection: 
- 
New respiratory (i.e., from sputum, pleural fluid or BAL specimen) pathogen(s) (i.e., 
pathogen(s) not present at baseline) identified in post-baseline culture(s) through the 
TOC Visit with persistent signs and symptoms of CABP (i.e., IACR of Failure at the 
TOC Visit, such that additional antibacterial therapy is necessary for the current 
episode of CABP). 
• Colonization: 
- 
New respiratory (i.e., from sputum, pleural fluid or BAL specimen) pathogen(s), (i.e., 
pathogen(s) not present at baseline) identified in at least 2 post-baseline cultures 

Nabriva Therapeutics AG 
Clinical Protocol NAB-BC-3781-3102 
 
 
V3.0:  17-Mar-2016 
Page 80 of 102 
Confidential Information 
through the TOC Visit but signs and symptoms of CABP have resolved, (i.e., IACR 
of Success at the TOC Visit, such that no additional antibacterial therapy is necessary 
for the current episode of CABP). 
• Development of Decreasing Susceptibility: 
- 
Increase in MIC (≥ 4x) or 6 mm decrease from baseline in disk inhibition zone 
diameter to the study drug received for a pathogen isolated at baseline and 
subsequently isolated from a blood or lower respiratory tract specimen. 
ECR plus improvement in vital signs (i.e., body temperature, blood pressure, heart rate, 
respiratory rate), if abnormal at Baseline will be evaluated in the ITT Analysis set.  If vital 
signs are normal at Baseline (i.e., not abnormal as per the definitions below), none can have 
worsened. 
Abnormal vital signs are defined as: 
• Fever: [defined as body temperature > 38.0 °C (100.4 °F) measured orally, > 38.5 °C 
(101.3 °F) measured tympanically, or > 39.0 °C (102.2 °F) measured rectally]  
• Hypothermia: [defined as body temperature < 35.0 °C (95.0 °F) measured orally, 
< 35.5 °C (95.9 °F) measured tympanically, or < 36.0 °C (96.8 °F) measured rectally] 
• Hypotension: defined as systolic blood pressure < 90 mmHg  
• Tachycardia: defined as heart rate > 100 bpm 
• Tachypnea: defined as respiratory rate > 20 breaths/min 
 
Exploratory evaluation of a variety of health utilization variables (e.g., length of hospital 
stay, duration of antibiotic therapy, discharge status, discharge destination) as well as a PRO 
instrument will be performed. Details for this exploratory analysis will be presented in a 
separate SAP and results will be presented in a stand-alone clinical study report. 
9.5 Demographic and Baseline Characteristics 
Enrollment, protocol deviations, and discontinuations from the study drug and the study will 
be summarized by treatment group.  Demographics (age, race, ethnicity and sex), medical 
and surgical history, baseline assessment of the clinical signs and symptoms, microbiological 
assessment, and study drug administration will also be summarized by treatment group.  
Differences between treatment groups will be analyzed using the chi-square or Fisher’s exact 
test for dichotomous variables and the Wilcoxon Rank Sum test for ordinal and continuous 
variables.  
9.6 Efficacy Analysis 
For all efficacy analyses, subject data will be analyzed in the group to which the subject was 
randomized.  For the stratified analysis of the primary efficacy outcome and for the primary 

Nabriva Therapeutics AG 
Clinical Protocol NAB-BC-3781-3102 
 
 
V3.0:  17-Mar-2016 
Page 81 of 102 
Confidential Information 
analysis for the EMA, subjects who are randomized to the wrong stratum will be analyzed in 
the stratum to which they were randomized.   
9.6.1 
Primary Efficacy Analysis 
The primary efficacy outcome (FDA) is the proportion of responders for ECR at 
96 ± 24 hours following the first dose of study drug in the ITT Analysis Set.  Each subject 
will be programmatically categorized as a Responder, Non-responder or Indeterminate based 
on data on the eCRF assessments of CABP signs and symptoms Subjects who are missing 
data required to determine an ECR or who are lost to follow up are defined as Indeterminate 
for the primary analysis and are included in the denominator for the calculation of the 
responder rate.  Thus, subjects with an ECR of Indeterminate are considered non-responders 
for the primary analysis.  The number and percentage of subjects in each treatment group in 
each response category will be reported.   
The null and alternative hypotheses are: 
H0: P1 - P2 ≤ - ∆ 
H1: P1 - P2 > - ∆ 
Where P1 = the primary efficacy outcome rate in the lefamulin group 
P2 = the primary efficacy outcome rate in the moxifloxacin group 
∆ = the non-inferiority margin 
The NI hypothesis test is a 1-sided hypothesis test performed at the 2.5 % level of 
significance.  This is based on the lower limit of the 2-sided 95 % confidence interval (CI) for 
the observed difference in the ECR (lefamulin group minus the moxifloxacin group).  The CI 
will be calculated using an unadjusted continuity corrected Z-statistic.  If the lower limit of 
the 95 % CI for the difference in responder rates in the ITT Analysis Set is greater 
than -10.0 %, the null hypothesis will be rejected and the NI of lefamulin to moxifloxacin 
will be concluded.   
Additional analyses of the primary efficacy outcome will be conducted.  ECR will be 
assessed separately across the geographic regions, prior antibiotic use, and PORT risk class 
strata.  For each geographic region, prior antibiotic use, and PORT risk class stratum, a 2-
sided 95% CI for the observed difference in ECR responder rates will be calculated for the 
ITT Analysis Set.  Sensitivity analyses of ECR include determination of a stratified 95% CI 
(adjusted for the randomization stratification factors) and considering all subjects with 
missing data (i.e., Indeterminates) at 96 ± 24 hours after the first dose of study drug as 
responders for ECR (these subjects are considered non-responders in the primary analysis).  
For the second sensitivity analysis, an unstratified 95% CI will be computed for the 
difference in the responder rates between lefamulin and moxifloxacin.  Subgroup analyses of 
the primary efficacy outcome will also be conducted for descriptive purposes and will be 
detailed in the SAP. For both ECR and IACR, additional analyses will be conducted whereby 
failures will be reclassified as Indeterminate if they received less than 48 hours of study 
medication.  

Nabriva Therapeutics AG 
Clinical Protocol NAB-BC-3781-3102 
 
 
V3.0:  17-Mar-2016 
Page 82 of 102 
Confidential Information 
For the EMA primary analysis (secondary analysis for the FDA), the number and percentage 
of subjects in each treatment group with an IACR of Success, Failure and Indeterminate (by 
definition Indeterminates are not included in the CE-TOC Analysis Set) at TOC will be 
reported in the mITT and CE-TOC Analysis.  Subjects who have an IACR of Failure at EOT 
will be considered to have an IACR of Failure at TOC.  The primary analysis for the EMA 
will utilize 2-sided stratified (for the randomization stratification factors) 95% CIs calculated 
using the method of Miettinen-Nurminen.  If the lower limit of the 95% CI for the difference 
in success rates in both the mITT and CE-TOC Analysis Sets is greater than -10%, the NI of 
lefamulin to moxifloxacin will be concluded.  Two-sided unstratified 95% CIs will be 
calculated for the difference in success rates at TOC in the mITT and CE-TOC Analysis Sets 
(FDA secondary outcome). 
Additional analyses of the EMA primary efficacy outcome will be conducted.  IACR at TOC 
will be assessed separately across the geographic regions, prior antibiotic use, and PORT risk 
class strata in the mITT and CE-TOC Analysis Sets.  For each geographic region, prior 
antibiotic use, and PORT risk class stratum, a 2-sided 95% CI for the observed difference 
success rates will be calculated for the ITT and CE-TOC Analysis Sets.  Sensitivity analyses 
of IACR include determination of unstratified 95% CI  and considering all subjects with 
missing data (i.e., Indeterminates) as successes for IACR (these subjects are considered 
failures in the EMA primary analysis).  For the second sensitivity analysis, a stratified 95% 
CI will be computed for the difference in the success rates between lefamulin and 
moxifloxacin. Subgroup analyses of the EMA primary efficacy outcome will also be 
conducted for descriptive purposes and will be detailed in the EMA SAP. 
9.6.2 
Secondary Efficacy Analyses 
The number and percentage of subjects categorized as Responder, Non-responder and 
Indeterminate for the primary FDA efficacy outcome of ECR will also be presented for the 
microITT Analysis Set and a 2-sided unstratified 95 % CI for the difference in responder rate 
will be calculated using a continuity-corrected Z-statistic.  However, the formal test of NI 
will be conducted in the weighted (based on the inverse variance of each effect size) pooled 
population from this study and a second study in CABP. 
The number and percentage of subjects in each treatment group with an IACR of Success, 
Failure and Indeterminate (by definition Indeterminates are not included in the ME-TOC 
Analysis Set) at TOC will be reported in the microITT and ME-TOC Analysis Sets.  Subjects 
who have an IACR of Failure at EOT will be considered to have an IACR of Failure at TOC.  
Two-sided unstratified 95 % CIs will be calculated for the difference in success rates.   
The By-Pathogen Microbiologic Response (by definition, subjects with an Indeterminate 
Microbiologic Response are excluded from the ME-TOC Analysis Set) will be provided for 
the microITT and ME-TOC Analysis sets at TOC. 
All-cause mortality (ACM) through Day 28 will also be summarized in the ITT Analysis Set.  
Subjects who are lost to follow-up will be considered deceased for this analysis.  A 2-sided 
unstratified 95 % CI will be calculated for the treatment difference in ACM.   

Nabriva Therapeutics AG 
Clinical Protocol NAB-BC-3781-3102 
 
 
V3.0:  17-Mar-2016 
Page 83 of 102 
Confidential Information 
9.6.3 
Additional Efficacy Analyses 
Additional efficacy analyses will be conducted to support the efficacy findings for the 
primary and secondary outcomes.  Confidence intervals for proportions will be determined 
for descriptive purposes, as indicated below, but no conclusions of NI will be made. 
The number and percentage of subjects who are a Responder for ECR, the number and 
percentage of subjects who have an IACR of Success at TOC, and the number and 
percentage of subjects who are a sustained response at LFU will be presented by baseline 
pathogen in the microITT Analysis Set, ME-TOC (IACR only) and ME-LFU (sustained 
success only) Analysis Sets. 
The number and percentage of subjects in each treatment group with an IACR of Success, 
Failure and Indeterminate (by definition subjects with an IACR of Indeterminate are not 
included in the CE-EOT Analysis Set) at EOT in the mITT and CE-EOT Analysis Sets.  
Two-sided unstratified 95 % CIs will be calculated for the difference in IACR success rates.  
The number and percentage of subjects with a Sustained Success, Relapse, Failure and 
Indeterminate response as assessed by the Investigator at the LFU Visit will be summarized 
for the mITT and CE-LFU Analysis Sets.  Failure is defined as a subject who had an IACR 
of Failure at the TOC Visit. 
The By-Subject Microbiologic Response (by definition, subjects with an Indeterminate 
Microbiologic Response are excluded from the ME-TOC Analysis Set) will be provided for 
the microITT and ME-TOC Analysis sets at TOC.  Two-sided unstratified 95 % CIs will be 
provided for the difference in the By-Subject Microbiologic Response success rate. 
Early Clinical Response, including improvement in vital signs at 96 ± 24 hours after the first 
dose of study drug will be derived programmatically from the eCRF assessment of CABP 
signs and symptoms data.  The number and percentage of subjects who are a Responder 
(including vital signs) will be tabulated by treatment group in the ITT Analysis Set.  A 2-
sided unstratified 95 % CI will be calculated for the treatment difference for the responder 
rate. 
9.7 Safety Analysis 
Safety will be evaluated in the Safety Analysis Set by presenting summaries of AEs, routine 
clinical laboratory evaluations, ECGs, and vital signs in the 2 treatment groups.  Subjects 
who receive the wrong study drug for their entire course of treatment will be analyzed in the 
group based on the drug received.   
Summary tables will be provided for all TEAEs.  A TEAE is defined as an AE with a start 
date and time on or after the first dose of study drug.  Adverse events will be coded using the 
Medical Dictionary for Regulatory Activities (MedDRA®).  The number and percentage of 
subjects with TEAEs will be tabulated by system organ class (SOC) and MedDRA Preferred 
Term for each treatment group and by severity and relationship to treatment. 
Adverse events leading to premature discontinuation from the study drug and serious TEAEs 
will be presented either in a table or a listing. 

Nabriva Therapeutics AG 
Clinical Protocol NAB-BC-3781-3102 
 
 
V3.0:  17-Mar-2016 
Page 84 of 102 
Confidential Information 
Change from baseline to each scheduled evaluation and the overall worst post-baseline in 
clinical laboratory variables will be summarized by treatment group.  The number and 
percent of subjects with treatment-emergent potentially clinically significant (PCS) 
laboratory values will be tabulated for each treatment group.  Treatment-emergent PCS 
laboratory tests are those in which the Baseline value is not PCS and the post-baseline value 
is PCS.  PCS will be defined based on the pre-specified criteria outlined in the SAP.  
Change from baseline to each scheduled evaluation and the overall worst post-baseline for 
RR interval, PR interval, QRS interval, QT interval, and QT interval corrected with 
Fridericia from the ECG will be summarized for each treatment group with the mean, 
standard deviation, minimum value, and maximum value.  The triplicate values will be 
averaged for each subject before analysis.  An outlier analysis will also be provided based on 
the worst post-baseline value. 
Descriptive statistics of vital signs and the change from baseline to each scheduled evaluation 
will be summarized by treatment group at each study visit and the worst overall post-
baseline.  The number and percent of subjects with treatment-emergent PCS values will be 
tabulated for each treatment group. 
9.8 Handling of Missing Data 
For the primary outcome measure (FDA), if any data field needed to determine ECR is 
missing, the subject will be assigned a response of Indeterminate.  Imputations for the 
missing times will be provided in the SAP. For analyses of the primary outcome, subjects 
with an indeterminate response are included in the denominator, and thus are considered 
Non-responders.  A sensitivity analysis of the primary outcome will be conducted in which 
subjects with an indeterminate response are considered Responders.   
For the outcome measure of IACR at EOT, TOC and LFU, missing data are considered as a 
response of Indeterminate.  For analysis in the ITT, mITT and microITT Analysis Sets, 
indeterminate outcomes are included in the denominator and are thus, considered clinical 
Failures.  By definition, subjects with an IACR of Indeterminate are excluded from the CE-
EOT, CE-TOC, CE-LFU, ME-EOT, ME-TOC, and ME-LFU Analysis Sets.  
A missing microbiological response is considered a presumed response based on the IACR. 
For analysis in the microITT Analysis Set, indeterminate outcomes are included in the 
denominator and are thus, considered microbiological failures.  By definition, subjects with 
an IACR of Indeterminate are excluded from the ME Analysis Sets.   
Handling of missing data for other efficacy and safety outcomes will be presented in the 
SAP. 
9.9 Pharmacokinetic Analyses 
Measured plasma concentrations of lefamulin and its main metabolite, BC-8041, will be 
summarized descriptively by the actual time point of collection.  Summary statistics in the 

Nabriva Therapeutics AG 
Clinical Protocol NAB-BC-3781-3102 
 
 
V3.0:  17-Mar-2016 
Page 85 of 102 
Confidential Information 
tabulation will include n, mean, standard deviation, CV [%], median, minimum and 
maximum.  
Population PK modeling will be used to determine the individual model-predicted 
concentrations of lefamulin.  Simulation of model output will enable descriptive statistical 
analysis of PK variables such as the Cmax, Cmin and AUC for lefamulin. 
A description of the population PK analysis will be described in a separate SAP.  Results of 
this analysis will be reported separately. 
9.10 Health Utilization Variables and Patient Reported Outcome 
Exploratory evaluation of a variety of health utilization variables (e.g., length of hospital 
stay, duration of antibiotic therapy, discharge status, discharge destination) as well as a PRO 
instrument, the SF-12, will be performed.  In addition, other PRO instruments may be 
utilized in this study, as feasible.  Details for this exploratory analysis will be presented in a 
separate SAP and results will be presented in a stand-alone clinical study report  
10 STUDY MONITORING 
10.1 Clinical Monitoring 
All aspects of the study will be carefully monitored by the Sponsor’s authorized individuals, 
acting as agents of the sponsor with respect to current Good Clinical Practice and Standard 
Operating Procedures for compliance with applicable government regulations.  These 
individuals will have access to all records necessary to ensure integrity of the data and will 
periodically review the progress of the study with the principal investigator. 
Frequent communication between the study site and the Sponsor is essential to ensure that 
the subject safety is monitored adequately.  The Investigator will make safety assessments on 
an ongoing basis.  The Sponsor’s medical monitor will review safety information from all 
study sites as it becomes available throughout the study.  Should any safety concerns be 
identified, the Data Monitoring Committee (DMC) will be asked to review the data and 
determine what action is recommended. 
10.2 Independent Data Monitoring Committee (DMC) 
An independent DMC will be constituted for this study to monitor important aspects of study 
conduct, including safety results on an ongoing basis.  The DMC will consist of 3 members 
who will be selected by the Sponsor but will be independent from the Sponsor.  The 
clinicians on the committee will not participate in the study as Principal or Co-investigators, 
and should be isolated from the study if their institution is a study site.  The DMC members 
receive no financial incentives for their participation, but are reimbursed only for customary 
consultative and administrative support fees.  
DMC meeting frequency and conduct is outlined in a separate DMC Charter.  An 
independent unblinded statistician will provide the committee with masked data for review 

Nabriva Therapeutics AG 
Clinical Protocol NAB-BC-3781-3102 
 
 
V3.0:  17-Mar-2016 
Page 86 of 102 
Confidential Information 
(treatment A versus treatment B), but will not be a member of the committee.  All members 
of the DMC will treat study data, reports, meeting discussions, and conclusions as 
confidential. 
11 IEC/IRB APPROVAL 
The Principal Investigator agrees to provide the Independent Ethics Committee 
(IEC)/Institutional Review Board (IRB) with all appropriate material, including a copy of the 
informed consent.  The study will not be initiated until the Investigator obtains written 
approval of the research plan (protocol) and the informed consent document from the 
appropriate IEC/IRB and copies of these documents are received by Nabriva Therapeutics 
AG.   
It is the Investigator’s responsibility to obtain IEC/IRB approval for all subsequent major 
changes to the protocol, in compliance with local law.  Appropriate reports on the progress of 
this study will be made by the Investigator to the IEC/IRB and Sponsor in accordance with 
applicable government regulations and in agreement with policy established by the Sponsor. 
12 ETHICAL CONDUCT OF THE STUDY 
This clinical study will be conducted in compliance with this Protocol, the guidelines of the 
World Medical Association Declaration of Helsinki in its revised edition (Fortaleza, Brazil, 
October 2013), the guidelines of International Conference on Harmonization (ICH) Good 
Clinical Practice (GCP) (CPMP/ICH/135/95), European Union (EU) Clinical Trials Directive 
2001/20/EC, EU Commission Directive 2005/28/EC, and Code of Federal Regulation (CFR) 
Title 21, CFR Part 50, 56 and 312, designated Standard Operating Procedures, and with local 
laws and regulations relevant to the use of new therapeutic agents in the country of conduct. 
13 INFORMED CONSENT 
The International Conference on Harmonization (ICH) has issued guidelines to provide 
protection for human subjects in clinical investigations.  The ICH Tripartite Guideline for 
Good Clinical Practice establishes the general requirements for informed consent. 
A properly executed, written informed consent in compliance with the terms of these 
guidelines shall be obtained from each subject before entering the study, or before 
performing any unusual or non-routine procedure in relation to the study.  The purpose of the 
study, procedures to be carried out, and potential hazards will be described to each potential 
subjects in non-technical terms.  Subjects (or their legally authorized representative) will be 
required to read, voluntarily sign, and date an informed consent form summarizing the 
discussion at Screening, and will be assured that they may withdraw from the study at any 
time without jeopardizing their medical care. 
Subjects (or their legally authorized representative) will sign and date 1 copy of the informed 
consent form which will be photocopied.  In accordance with local regulations, the original 
and copies of the signed and dated consent may be retained by the subject (or their legally 
authorized representative) and/or retained on file by the Investigator, as applicable.  

Nabriva Therapeutics AG 
Clinical Protocol NAB-BC-3781-3102 
 
 
V3.0:  17-Mar-2016 
Page 87 of 102 
Confidential Information 
The consent form must be approved by the appropriate IEC/IRB and Sponsor before study 
initiation at a study site.  Any subsequent changes to the approved informed consent form 
must be reviewed and approved by the appropriate IEC/IRB and Sponsor before 
implementation. 
14 QUALITY ASSURANCE AND QUALITY CONTROL 
Standard Operating Procedures belonging to Nabriva Therapeutic AG or designee(s) will be 
adhered to for all activities relevant to the quality of the study and are routinely monitored by 
the Quality Assurance (QA) Division.  
Data will undergo quality control checks prior to clinical database lock.  Sponsor-designated, 
independent monitors will be responsible for the monitoring of the study and its data within 
the eCRFs. 
A QA audit of this study may be conducted by the Sponsor or Sponsor’s designee.  The QA 
auditor will have access to all medical records, the Investigator’s study-related files and 
correspondence, information in the informed consent documentation of this study, and study 
drug storage facilities.  
An inspection of this study may be conducted by a regulatory agency.  The Investigator 
agrees to contact the Sponsor as soon as possible, but not later than within 1 week, upon 
notification of an inspection by a regulatory agency.  The Investigator agrees to allow the 
Inspector direct access to all relevant documents and to allocate his/her time and that of study 
personnel to the Inspector to discuss findings in any relevant issues.  The Investigator will 
allow Sponsor personnel to be present as an observer during a regulatory inspection, if 
requested.  
15 DATA HANDLING AND RECORD KEEPING  
15.1 Data Handling 
Data will be recorded at sites using eCRFs and reviewed by the Sponsor or designee during 
monitoring visits.  The recorded data in the EDC system will be verified with source 
documents.  All corrections or changes made to any study data must be appropriately tracked 
in an audit trail in the EDC system.  eCRFs will be considered complete when all missing, 
incorrect, and/or inconsistent data has been accounted for.  Data collected at baseline will 
only be entered into the eCRF if the subject is eligible for study participation following 
review of the data by the Investigator or designee.  
Adverse events, concomitant medication data and clinical observations will be in the 
subjects’ hospital notes, or recorded on source data forms, and will be transferred into the 
eCRF after assessment by the Investigator or designee. 
Data produced by automatic devices with original print-outs (e.g., clinical laboratory test 
results, ECG traces, BP measurements) will be included in the source documentation.  
Clinical laboratory parameters are to be reviewed, signed and dated by the Investigator or 

Nabriva Therapeutics AG 
Clinical Protocol NAB-BC-3781-3102 
 
 
V3.0:  17-Mar-2016 
Page 88 of 102 
Confidential Information 
designee.  Any results outside the normal range should be designated by the Investigator or 
designee as not clinically significant (NCS) or clinically significant (CS). 
15.2 Subject Confidentiality 
Investigator and his/her staff will be required to manage subject data collected for the study 
in accordance with applicable laws and regulations on personal data protection.   
US:  All US-based investigational sites and laboratories or entities providing support for this 
study, must, where applicable, comply with the Health Insurance Portability and 
Accountability Act (HIPAA) of 1996.  An investigational site that is not a Covered Entity as 
defined by HIPAA must provide documentation of this fact to Nabriva Therapeutics AG. 
EU:  Data collected during this study may be used to support the development, registration or 
marketing of lefamulin.  Nabriva Therapeutics AG will control all data collected during the 
study, and will abide by the EU Directive on Data Privacy concerning the processing and use 
of subjects’ personal data.  For the purpose of data privacy legislation, Nabriva Therapeutics 
AG will be the data controller. 
After subjects have consented to take part in the study their medical records and the data 
collected during the study will be reviewed by Nabriva Therapeutics AG or its 
representatives.  These records and data may, in addition, be reviewed by the following: 
independent auditors who validate the data on behalf of Nabriva Therapeutics AG; third 
parties with whom Nabriva Therapeutics AG may develop, register or market lefamulin; 
national or local regulatory authorities and the IRB/IECs that gave approval for this study to 
proceed. 
Subjects will be known by a unique number; however, their date of birth can also be 
collected if not in contradiction with any requirements (e.g., from IECs) and used to assist 
Nabriva Therapeutics AG to verify the accuracy of the data, for example, that the laboratory 
results are assigned to the correct subject.  The results of this study may be recorded and 
transferred to and used in other countries throughout the world, which may not afford the 
same level of protection that applies within the EU.  The purpose of any such transfer would 
be to support regulatory submissions in other countries. 
15.3 Computer Systems 
Data will be processed using a validated computer system conforming to regulatory 
requirements. 
15.4 Data Entry 
Data must be recorded using the EDC system as the study is in progress.  All study personnel 
must log into the system using their secure user name and password in order to enter, review, 
or correct study data.  These procedures must comply with the Title 21 Code of Federal 
Regulations (21 CFR Part 11) for US sites and EU Directives 2001/20/EC and 2005/28/EC 
for EU sites.  All passwords will be strictly confidential.  

Nabriva Therapeutics AG 
Clinical Protocol NAB-BC-3781-3102 
 
 
V3.0:  17-Mar-2016 
Page 89 of 102 
Confidential Information 
15.5 Data Validation 
Validation checks programmed within the EDC system as well as supplemental validation 
performed via review of the downloaded data will be applied to the data in order to ensure 
accurate, consistent, and reliable data.  Data identified as erroneous, or data that are missing, 
will be referred to the investigative site for resolution through data queries. 
eCRFs must be reviewed and electronically signed by the Investigator who signed the 
protocol. 
15.6 Record Keeping  
Raw data generated in connection with this study as well as an original copy of the final 
clinical study report, will be retained in archive until at least 5 years after the last approval of 
a marketing application in an ICH region and until there are no pending or contemplated 
marketing applications in an ICH region or at least 5 years have elapsed since the formal 
discontinuation of clinical development of lefamulin.  These documents will be retained for a 
longer period if required by the applicable regulatory requirements or by an agreement with 
the Sponsor.  It is the responsibility of the Sponsor to inform the Investigator/Institution as to 
when these documents no longer need to be retained. 
As required under European Directive 2005/28/EC, Article 17, all ‘essential documents’ (as 
described in the ICH GCP Guidelines) must be retained by Nabriva Therapeutics AG and the 
Investigator for at least 5 years after the completion of the clinical study.  Therefore all 
studies, independent of where they were conducted in the world, must follow this 
requirement in the event a submission is ever made in the EU.  These documents may be 
retained for a longer period, however, if required by the applicable regulatory requirements 
or by an agreement with Nabriva Therapeutics AG.  It is the responsibility of Nabriva 
Therapeutics AG to inform the Investigator as to when these documents no longer need to be 
retained.  The Investigator must obtain written permission from Nabriva Therapeutics AG 
prior to the destruction of any study document.  
The retention of investigator study records is an investigator responsibility and Nabriva 
Therapeutics AG will neither arrange nor pay for this activity. Any transfer of ownership of 
the content of the clinical trial master file is the responsibility of the investigator or site 
representative, and shall be documented.  The new owner shall assume the responsibilities set 
forth in the applicable regulations. 
These records must be made available at reasonable times for inspection and duplication, if 
required, by a properly authorized representative of the US Food and Drug Administration 
(FDA) in accordance with 21 CFR 312.68 or other national or foreign Regulatory Authorities 
in accordance with regulatory requirements.  
16 TERMINATION OF STUDY 
The Sponsor reserves the right to discontinue this study at any time. 

Nabriva Therapeutics AG 
Clinical Protocol NAB-BC-3781-3102 
 
 
V3.0:  17-Mar-2016 
Page 90 of 102 
Confidential Information 
17 FINANCING AND INSURANCE 
The costs necessary to perform the study will be agreed with each Investigator and will be 
documented in a separate financial agreement that will be signed by the Investigator and 
Nabriva Therapeutics AG (or designee), prior to the start of the study.  A statement regarding 
insurance/indemnity such as Association of British Pharmaceutical Industry (ABPI) should 
also be included. 
The Investigator will be required to disclose any financial arrangement whereby the value of 
the compensation for conducting the study could be influenced by the results or outcome of 
the study.  The following information will be collected: any significant payments of other 
sorts from Nabriva Therapeutics AG, (e.g., money to fund ongoing research, compensation in 
the form of equipment, retainer for ongoing consultation or honoraria); any proprietary 
interest in lefamulin; any significant equity interest in Nabriva Therapeutics AG as defined in 
21 CFR 54 2(b). 
In consideration of participation in the study, Nabriva Therapeutics AG will pay the 
Investigator or nominated payee the sums set out in the payment schedule attached to the 
Investigator agreement.  
18 PUBLICATION POLICY 
It is intended that the results of the study may be published as scientific literature.  Results 
may also be used in submissions to Regulatory Authorities.  The following conditions are to 
protect commercial confidential materials (e.g., patents, etc.), not to restrict publication. 
All information concerning lefamulin (such as patent applications, formulae, manufacturing 
processes, basic scientific data, or formulation information supplied to the Investigator by 
Nabriva Therapeutics AG and not previously published) is considered confidential by 
Nabriva Therapeutics AG and shall remain the sole property of Nabriva Therapeutics AG.  
The Investigator agrees not to use it for other purposes without Nabriva Therapeutics AG 
written consent. 
It is understood by the Investigator that Nabriva Therapeutics AG will use the information 
developed in this clinical study in connection with the development of lefamulin and, 
therefore, may be disclosed as required to other Nabriva Therapeutics AG Investigators or 
any appropriate international Regulatory Authorities.  In order to allow for the use of 
information derived from this clinical study, the Investigator understands that he/she has an 
obligation to provide Nabriva Therapeutics AG with complete test results and all data 
developed during this study. 
All manuscripts, abstracts or other modes of presentation arising from the results of the study 
must be reviewed and approved in writing by Nabriva Therapeutics AG in advance of 
submission.  The review is aimed at protecting Nabriva Therapeutics AG's proprietary 
information existing either at the date of the commencement of the study or generated during 
the study. 

Nabriva Therapeutics AG 
Clinical Protocol NAB-BC-3781-3102 
 
 
V3.0:  17-Mar-2016 
Page 91 of 102 
Confidential Information 
The detailed obligations regarding the publication of any data shall be set out in the 
agreement between each Investigator and Nabriva Therapeutics AG. 
 
 

Nabriva Therapeutics AG 
Clinical Protocol NAB-BC-3781-3102 
 
 
V3.0:  17-Mar-2016 
Page 92 of 102 
Confidential Information 
19 LIST OF REFERENCES 
 
Arnold et al., 2007. 
Arnold FW, Summersgill JT, Lajoie AS, et al. A worldwide perspective of atypical 
pathogens in community-acquired pneumonia. Am J Respir Crit Care Med. 2007; 
175(10):1086-1093. 
 
Barrera et al., 2016. 
Barrera CM, Mykietiuk A, Metev H, et al. Efficacy and safety of oral solithromycin versus 
oral moxifloxacin for treatment of community-acquired bacterial pneumonia: a global, 
double-blind, multicentre, randomised, active-controlled, non-inferiority trial (SOLITAIRE-
ORAL). Lancet Infect Dis. 2016; Feb 4. pii: S1473-3099(16)00017-7. doi: 10.1016/S1473-
3099(16)00017-7. [Epub ahead of print] 
 
Bhavnani et al., 2005. 
Bhavnani SM, Hammell JP, Cirincione BB, Wikler MA, Ambrose PG. Use of 
pharmacokinetic-pharmacodynamic target attainment analyses to support Phase 2 and 3 
dosing strategies for doripenem. Antimicrob Agents Chemother. 2005; 49(9):3944-3947. 
 
Bhavnani et al., 2009. 
Bhavnani SM, Lawrence L, Burak E, Ambrose PG. Clinical trial dose selection for 
dalafloxacin (DFX) for complicated skin and skin-structure infections (cSSSI). Poster 
presented at: 49th ICAAC; 2009 Sep 12-15; San Francisco, CA, USA. A1-1942. 
 
CDC, 2013. 
CDC, Leading Causes of Death (2013). http://www.cdc.gov/nchs/fastats/leading-causes-of-
death.htm (last access: 29.10.2014). 
 
Cempra, 2015. 
Cempra, Inc. 16-Jan-2015. Cempra announces positive topline phase 3 clinical results for 
intravenous solithromycin in the treatment of community-acquired bacterial pneumonia 
[Press release]. Retrieved from 
http://investor.cempra.com/releasedetail.cfm?releaseid=936994 
 
Dalhoff, 2012. 
Dalhoff A. Resistance surveillance studies: a multifaceted problem–the fluoroquinolone 
example. Infection. 2012; 40(3):239-262. 
 
Davidovich et al., 2007. 
Davidovich C, Bashan A, Auerbach-Nevo T, Yaggie RD, Gontarek RR, Yonath A. Induced-
fit tightens pleuromutilins binding to ribosomes and remote interactions enable their 
selectivity. Proc Natl Acad Sci USA. 2007; 104(11):4291-4296. 
 

Nabriva Therapeutics AG 
Clinical Protocol NAB-BC-3781-3102 
 
 
V3.0:  17-Mar-2016 
Page 93 of 102 
Confidential Information 
FDA, 2011. 
FDA Anti-infective Drugs Advisory Committee (03-Nov-2011). Endpoints and clinical trial 
issues in community-acquired bacterial pneumonia. Recommendations to FDA for interim 
endpoints for clinical trials in community-acquired bacterial pneumonia (document dated, 
26-Aug-2011).  Prepared by: Foundations for the National Institutes of Health Biomarkers 
Consortium Project Team. CABP Docket ID: FDA-2009D0136. Available at: 
http://www.fda.gov/downloads/advisorycommittees/committeesmeetingmaterials/drugs/anti-
infectivedrugsadvisorycommittee/ucm275823.pdf.  
 
Fine et al., 1996. 
Fine MJ, Smith MA, Carson CA, et al. Prognosis and outcomes of patients with community-
acquired pneumonia. A meta-analysis. JAMA. 1996; 257(2):134-141. 
 
Fine et al., 1997. 
Fine MJ, Auble TE, Yealy DM, et al. A prediction rule to identify low-risk patients with 
community-acquired pneumonia. N Engl J Med. 1997; 336(4):243-250. 
 
Francis et al., 2005. 
Francis JS, Doherty MC, Lopatin U, et al. Severe community-onset pneumonia in healthy 
adults caused by methicillin-resistant Staphylococcus aureus carrying the Panton-Valentine 
leukocidin genes. Clin Infect Dis. 2005; 40(1):100-107. 
 
Gillet et al., 2007. 
Gillet Y, Vanhems P, Lina G, et al. Factors predicting mortality in necrotizing community-
acquired pneumonia caused by Staphylococcus aureus containing Panton-Valentine 
leukocidin. Clin Infect Dis. 2007; 45(3):315-321. 
 
Hidron et al., 2009. 
Hidron AI, Low CE, Honig EG, Blumberg HM. Emergence of community-acquired 
meticillin-resistant Staphylococcus aureus strain USA300 as a cause of necrotising 
community-onset pneumonia. Lancet Infect Dis. 2009; 9(6):384-392. 
 
Kollef et al., 2005. 
Kollef MH, Shorr A, Tabak YP, Gupta V, Liu LZ, Johannes RS. Epidemiology and outcomes 
of health-care-associated pneumonia: results from a large US database of culture-positive 
pneumonia. Chest. 2005; 128(6):3854-3862. 
 
Lim et al., 2009. 
Lim WS, Baudouin SV, George RC, et al. The British Thoracic Society guidelines for the 
management of community acquired pneumonia in adults: update 2009. Thorax. 2009; 
64(Suppl 3):iii1-iii50. 
 

Nabriva Therapeutics AG 
Clinical Protocol NAB-BC-3781-3102 
 
 
V3.0:  17-Mar-2016 
Page 94 of 102 
Confidential Information 
Liu et al., 2014. 
Liu X, Jiang Y, Chen X, Li J, Shi D, Xin D. Drug resistance mechanisms of Mycoplasma 
pneumoniae to macrolide antibiotics. BioMed Research International, vol. 2014, Article ID 
320801, 7 pages, 2014. doi:10.1155/2014/320801. 
 
Mandell et al., 2007. 
Mandell LA, Wunderink RG, Anzueto A, et al. Infectious Diseases Society of 
America/American Thoracic Society consensus guidelines on the management of 
community-acquired pneumonia in adults. Clin Infect Dis. 2007; 44(Suppl 2):S27-S72. 
 
Oldach et al., 2015.   
Oldach D, Barrera C, Mykietiuk A, Metev H, Nitu MF, Karimjee N, et al. SOLITAIRE-Oral: 
results of a global phase 3 trial comparing oral solithromycin versus oral moxifloxacin for 
treatment of community-acquired bacterial pneumonia (CABP) in adults.  Abstract (oral 
session) presented at: 25th ECCMID; 2015 Apr 25-28; Copenhagen, Denmark. LBOS0239c. 
 
Paukner et al., 2012. 
Paukner S, Ivezic-Schoenfeld Z, Tack KJ, Sahm D, Prince WT. Microbiological activity and 
outcome of the pleuromutilin BC-3781 in a clinical phase 2 trial in acute bacterial skin and 
skin structure infections (ABSSSI). Poster presented at: 52nd ICAAC; 2012 Sep 9-12; San 
Francisco, CA, USA. L-1660. 
 
Paukner et al., 2013. 
Paukner S, Sader HS, Ivezic-Schoenfeld Z, Jones RN. Antimicrobial activity of the 
pleuromutilin antibiotic BC-3781 against bacterial pathogens isolated in the SENTRY 
antimicrobial surveillance program in 2010. Antimicrob Agents Chemother. 2013; 
57(9):4489-4495. 
 
Pfaller et al., 2012. 
Pfaller MA, Farell DJ, Sader HS, Jones RN. AWARE Ceftaroline Surveillance Program 
(2008-2010): trends in resistance patterns among Streptococcus pneumoniae, Haemophilus 
influenzae, and Moraxella catarrhalis in the United States. Clin Infect Dis. 2012; 55 (Suppl 
3):S187-S193. 
 
Prince et al., 2010. 
Prince WT, Wicha WW, Strickmann DB, Moschetti V, Obermayr F, Novak R. Safety, 
tolerance and pharmacokinetics of single and repeat doses of BC-3781, a novel antimicrobial. 
Poster presented at: 20th ECCMID; 2010 Apr 10-12; Vienna, Austria. P906. 
 
Prince et al., 2013. 
Prince WT, Ivezic-Schoenfeld Z, Lell C, et al. Phase II clinical study of BC-3781, a 
pleuromutilin antibiotic, in treatment of patients with acute bacterial skin and skin structure 
infections. Antimicrob Agents Chemother. 2013; 57(5):2087-2094. 
 

Nabriva Therapeutics AG 
Clinical Protocol NAB-BC-3781-3102 
 
 
V3.0:  17-Mar-2016 
Page 95 of 102 
Confidential Information 
Rubino et al., 2015. 
Rubino CM, Xue B, Bhavnani SM, et al. Population pharmacokinetic analyses for BC-3781 
using phase 2 data from patients with acute bacterial skin and skin structure infections. 
Antimicrob Agents Chemother. 2015; 59(1):282-288. 
 
Sader et al., 2012. 
Sader HS, Paukner S, Ivezic-Schoenfeld Z, Biedenbach DJ, Schmitz FJ, Jones RN. 
Antimicrobial activity of the novel pleuromutilin antibiotic BC-3781 against organisms 
responsible for community-acquired respiratory tract infections (CARTIs). J Antimicrob 
Chemother. 2012; 67(5):1170-1175.  
 
Van Wart et al., 2009. 
Van Wart S, Andes DR, Ambrose PG, Bhavnani SM. Pharmacokinetic-pharmacodynamic 
modeling to support doripenem dose regimen optimization for critically ill patients. Diagn 
Microbiol Infect Dis. 2009; 63:409-414. 
 
Waites and Talkington, 2004. 
Waites KB, Talkington DF. Mycoplasma pneumoniae and its role as a human pathogen. Clin 
Microbiol Rev. 2004; 17(4):697-728. 
 
Wicha et al., 2010. 
Wicha WW, Lell C, Obermayr F, Logan DK, Prince WT. An age and gender study 
investigating the safety, tolerance and pharmacokinetics of BC-3781. Poster presented at: 
50th ICAAC; 2010 Sep 12-15; Boston, MA, USA. A1-019 
 
Wicha et al., 2013. 
Wicha WW, Lell C, Strickmann DB, Heilmayer W, Ivezic-Schoenfeld Z, Prince WT. Safety, 
tolerability and pharmacokinetics of orally administered BC 3781, a novel antimicrobial. 
Poster presented at: 53rd ICAAC; 2013 Sep 10-13; Denver, CO, USA. A-012. 
 
Zeitlinger et al., 2011. 
Zeitlinger M, Obermayr F, Burian A, et al. The pharmacokinetics of BC-3781 in muscle and 
adipose tissue in healthy subjects. Poster presented at: 51st ICAAC; 2011 Sep 17-20; 
Chicago, IL, USA. A1-1761a. 
 
Zeitlinger et al., 2016. 
Zeitlinger M, Schwameis R, Burian A, et al. Simultaneous assessment of the 
pharmacokinetics of a pleuromutilin, lefamulin, in plasma, soft tissues and pulmonary 
epithelial lining fluid. J Antimicrob Chemother. 2016; Jan 7. pii: dkv442. [Epub ahead of 
print] 
 
 
 

Nabriva Therapeutics AG 
Clinical Protocol NAB-BC-3781-3102 
 
 
V3.0:  17-Mar-2016 
Page 96 of 102 
Confidential Information 
20 APPENDICES 
 
Appendix 1 
Clinical Laboratory Tests (Safety) 
Appendix 2 
Short Acting Antibiotics 
Appendix 3 
Closely Monitored CYP3A4 Substrates and P-Glycoprotein Substrates 
(excluding strong CY3A inducers and inhibitors and excluding strong P-
glycoprotein inhibitors) 
Appendix 4 
Prohibited Strong P-Glycoprotein Inhibitors and Strong CYP3A Inducers 
and Inhibitors 
Appendix 5 
Drugs That Prolong QT 
 
 
 

Nabriva Therapeutics AG 
Clinical Protocol NAB-BC-3781-3102 
 
 
V3.0:  17-Mar-2016 
Page 97 of 102 
Confidential Information 
Appendix 1 
Clinical Laboratory Tests (Safety) 
Blood and urine samples for the following laboratory tests will be sent to a central 
laboratory for testing.    
 
Hematology 
Complete blood count (CBC) with RBC indices and WBC differential 
Platelet count 
Chemistry 
BUN 
Creatinine 
Glucose 
Sodium 
Potassium 
Chloride 
Calcium 
Magnesium 
Phosphorus 
AST 
ALT 
GGT 
Alkaline Phosphatase 
CPK 
Total Bilirubin 
Direct Bilirubin 
Uric Acid 
Albumin 
Total Protein 
Urinalysis 
Specific gravity 
pH, glucose, protein, blood, ketones, bilirubin and leukocyte esterase by dipstick 
Microscopic examination (all samples) 
Other tests 
Procalcitonin 
 
Testing at Screening Only 
Serum pregnancy test 
Urine pregnancy test (testing kit provided by central laboratory; test to be performed at 
the local site prior to randomization) 
 
 
 
 

Nabriva Therapeutics AG 
Clinical Protocol NAB-BC-3781-3102 
 
 
V3.0:  17-Mar-2016 
Page 98 of 102 
Confidential Information 
Appendix 2 
Short Acting versus Long Acting Antibiotics 
 
Short-acting 
Long-acting 
Cephalosporins 
Cefaclor, Cefadroxil, Cefdinir, Cefepime, 
Cefixime (200 mg), Cefotaxime, Cefpodoxime, 
Cefprozil, Ceftazadime, Ceftibuten, Cefditoren, 
Cefruoxime, Cephalexin, Loracarbef 
Cefixime (400 mg), Ceftriaxone 
Fluoroquinolones 
Ciprofloxacin, Norfloxacin 
Gatifloxacin, Gemifloxacin, Grepafloxacin, 
Levofloxacin, Moxifloxacin, Sparfloxacin 
Macrolides and Ketolides 
Clarithromycin, Erythromycin, Roxithromycin 
Azithromycin, Clarithromycin XL (extended 
release), Dirithromycin, Telithromycin 
Penicillins and Carbapenems 
Amoxicillin, Amoxicillin-Clavulanate, 
Amoxicillin-Sulbactam, Ampicillin, Ampicillin-
Sulbactam, Dicloxacillin, Imipenem, 
Meropenem, Nafcillin, Oxacillin, Penicillin-G, 
Penicillin-V, Piperacillin, Piperacillin-
Tazobactam, Ticaracillin-Clavulanate 
Ertapenem, Penicillin-G, Benzathine/Procaine 
Tetracyclines 
Doxycycline (100 mg), Minocycline, 
Tetracycline 
Doxycycline (200 mg), Minocycline Extended 
Release 
 
 
 
 

Nabriva Therapeutics AG 
Clinical Protocol NAB-BC-3781-3102 
 
 
V3.0:  17-Mar-2016 
Page 99 of 102 
Confidential Information 
Appendix 3 
Closely Monitored CYP3A4 Substrates and P-
Glycoprotein Substrates (excluding strong CY3A 
inducers and inhibitors and excluding strong P-
glycoprotein inhibitors) 
Closely Monitored CYP3A4 Substrates 
Alfentanyl 
Domperidone 
Pimozide 
Alprazolam 
Eplerenone 
Progesterone 
Amiodipine 
Estradiol 
Propranolol 
Aprepitant 
Fentanyl 
Quetiapine 
Aripiprazole 
Finasteride 
Quinine 
Astemizole 
Gleevec 
Reserpine 
Buspirone 
Haloperidol 
Salmeterol 
Cafergot 
Hydrocortisone 
Sildenafil 
Caffeine 
Lercanidipine 
Sirolimus 
Chlorpheniramine 
Lidocaine 
Terfenadine 
Cilostazol 
Methadone 
Testosterone 
Cocaine 
Midazolam 
Trazodone 
Codeine 
Nateglinide 
Triazolam 
Dapsone 
Nifedipine 
Zaleplon 
Dexamethasone 
Nisoldipine 
Ziprasidone 
Dextromethorphan 
Nitrendipine 
Zolpidem 
Docetaxel 
Ondansetron 
 
 
 

Nabriva Therapeutics AG 
Clinical Protocol NAB-BC-3781-3102 
 
 
V3.0:  17-Mar-2016 
Page 100 of 102 
Confidential Information 
 
Closely Monitored P-Glycoprotein Substrates 
Apixaban 
Fexofenadine 
Ranitidine 
Carvedilol 
Fosamprenavir 
Rivaroxaban 
Cimetidine 
Ivermectin 
Saxagliptin 
Colchicine 
Ledipasvir 
Silodosin 
Dabigatran 
Loperamide 
Sitagliptin 
Daclatasvir 
Losartan 
Sofosbuvir 
Dasabuvir 
Maraviroc 
Tetracycline  
Dexamethasone  
Methylprednisolone 
Tipranavir 
Digoxin  
Methotrexate  
Tolvaptan 
Domperidone 
Morphine 
Umeclidinium 
Edoxaban 
Ombitasvir 
Vecuronium  
Empagliflozin 
Paliperidone 
Vilanterol 
Estradiol 
Paritaprevir  
 
Ezetimibe 
Prazosin 
 
 
 
 

Nabriva Therapeutics AG 
Clinical Protocol NAB-BC-3781-3102 
 
 
V3.0:  17-Mar-2016 
Page 101 of 102 
Confidential Information 
Appendix 4 
Prohibited Strong P-Glycoprotein Inhibitors and Strong 
CYP3A Inducers and Inhibitors 
Prohibited Strong P-Glycoprotein Inhibitors 
Amiodarone  
Indinavir  
Ranolazine  
Atorvastatin  
Itraconazole  
Reserpine 
Boceprevir  
Ketoconazole  
Ritonavir  
Bromocriptine  
Linagliptin  
Saquinavir  
Captopril  
Lopinavir and ritonavir  
Simeprevir  
Carvedilol  
Lovastatin  
Simvastatin  
Cobicistat  
Meperidine  
Suvorexant  
Conivaptan  
Methadone 
Tacrolimus  
Cyclosporine  
Nelfinavir 
Tamoxifen  
Diltiazem  
Nicardipine  
Telaprevir  
Doxazosin  
Pentazocine  
Ticagrelor  
Dronedarone  
Progesterone 
Verapamil  
Felodipine  
Quercetin  
 
Fluvastatin  
Quinidine 
 
 
 
Prohibited Strong CYP3A Inhibitors 
Prohibited Strong CYP3A Inducers 
Indinavir 
Efavirenz 
Nelfinavir 
Nevirapine 
Ritonavir 
Phenobarbital 
Itraconazole 
Phenytoin 
Ketoconazole 
Pioglitazone 
Nefazodone 
Rifabutin 
Saquinavir 
Rifampin 
Suboxone 
St. John’s Wort 
Carbamazepine 
Troglitazone 
 

Nabriva Therapeutics AG 
Clinical Protocol NAB-BC-3781-3102 
 
 
V3.0:  17-Mar-2016 
Page 102 of 102 
Confidential Information 
Appendix 5 
Drugs That Prolong QT 
Anticonvulsants 
Fosphenytoin; Felbamate 
Antihistamines 
Azelastine, Clemastine 
Anti-infectives 
Amantadine, Clarithromycin, Chloroquine, Foscarnet, 
Erythromycin, Halofantrine, Mefloquine, Pentamidine, 
Sparfloxacin, Quinine, Trimethoprim-
Sulfamethoxazole, Ketoconazole 
Antineoplastics 
Tamoxifen 
Cardiovascular 
Antiarrhythmics 
Amiodarone, Bretylium, Disopyramide, Flecainide, 
Ibutilide, Procainamide, Quinidine, Sotalol, Dofetilide  
Calcium Channel Blockers 
Bepridil, Israpidine, Nicardipine 
Diuretics 
Indapamide, Moexipril/ hydrochlorothiazide 
Hormones 
Octreotide, Vasopressin 
Immunosuppressives 
Tacrolimus 
Migraine: Serotonin Receptor Agonists 
Zolmitriptan, Naratriptan, Sumatriptan 
Muscle Relaxants 
Tizanidine 
Narcotic Detoxification 
Levomethadyl 
Psycotherapeutics 
Antidepressants 
Amitriptyline, Desipramine, Fluoxetine, Imipramine, 
Venlafaxine 
Antipsychotics 
Chlorpromazine, Haloperidol, Pimozide, Quetiapine, 
Risperidone, Thioridazine 
Antianxiety 
Doxepin 
Antimanic 
Lithium 
Respiratory (Sympathomimetics) 
Salmeterol 
Sedative/Hypnotics 
Chloral hydrate 
Note: List not exhaustive