LEAP2: Study to Compare Lefamulin to Moxifloxacin for the Treatment of Adults With Pneumonia

• Sponsor: Nabriva Therapeutics AG (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02813694
• Collaborator: (none)
• Enrollment: 738
• Locations: 155
• Arms: 2
• Actual Duration (Months): 17
• Patients Per Site: 4.8
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

This study evaluates the safety and efficacy of lefamulin, a pleuromutilin, for the treatment of adults with moderate community-acquired bacterial pneumonia

Condition or Disease	Intervention/Treatment	Phase
Community Acquired Pneumonia	Drug: lefamulin; Drug: Moxifloxacin	Phase 3

Detailed Description

Lefamulin is a potent, semi-synthetic antibacterial belonging to a novel class known as the pleuromutilins. The oral dosage form of lefamulin is under investigation in this study. Lefamulin's in vitro antibacterial profile includes the most important bacterial pathogens causing respiratory tract infection (RTI). The antibacterial spectrum comprises S. pneumoniae, H. influenzae, M. catarrhalis, the atypical respiratory pathogens L. pneumophila,

1. pneumoniae, and M. pneumoniae, S. aureus including MRSA and CA-MRSA, ß-haemolytic streptococci including S. pyogenes and S. agalactiae, and Enterococcus faecium including vancomycin-resistant enterococci (VRE). Moreover, as demonstrated in cross-resistance studies, lefamulin remains active against clinical isolates resistant to the following antimicrobial(s) (classes): macrolides, lincosamides, streptogramin B, oxazolidinones, tetracyclines, ß lactams, quinolones, trimethoprim-sulfametoxazole, mupirocin, and vancomycin.

Study Design

• Study Type: Interventional
• Actual Enrollment: 738 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official 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
• Actual Study Start Date: Aug 1, 2016
• Actual Primary Completion Date: Jan 1, 2018
• Actual Study Completion Date: Jan 1, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: lefamulin oral lefamulin, 600mg	Drug: lefamulin; antibacterial agent; Other Names: BC-3781
Active Comparator: Moxifloxacin oral moxifloxacin, 400mg	Drug: Moxifloxacin; antibacterial agent; Other Names: Avelox

Outcome Measures

Primary Outcome Measures

1. Early Clinical Response (ECR) [96 hours +/- 24 hours after first dose of study drug]

   ECR was defined as survival with improvement in at least 2 signs and symptoms of CABP (relative to baseline), no worsening of any CABP sign or symptom, and no use of concomitant antibiotics for the treatment of CABP through the ECR assessment

Secondary Outcome Measures

1. Investigator's Assessment of Clinical Response (IACR) [IACR was assessed at the Test-of-Cure Visit; 5 to 10 days after last dose of study drug]

   IACR was defined as resolution or improvement of a subject's clinical signs and symptoms such that no additional antibacterial therapy was administered for the treatment of the current episode of CABP

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

Each subject must:

1. Be male or female at least 18 years of age.

2. Provide written informed consent and be willing and able to adhere to the study-specified procedures and restrictions.

3. Have an acute illness (less than or equal to 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.

1. 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).

1. 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.

1. 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).

2. 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.

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.

2. Require concomitant systemic antibacterial therapy potentially effective against CABP pathogens.

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).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	1080	Beverly Hills	California	United States
2	Site 1065	Fresno	California	United States	93701
3	1078	Northridge	California	United States
4	Site 1072	Oxnard	California	United States	93030
5	Site 1070	Sacramento	California	United States	95817
6	1079	Sherman Oaks	California	United States
7	Site 1053	Sylmar	California	United States	91342
8	Site 1064	DeBary	Florida	United States	32713
9	Site 1052	DeLand	Florida	United States	32720
10	1076	Miami	Florida	United States
11	Site 1051	Michigan City	Indiana	United States	46360
12	Site 1057	Natchitoches	Louisiana	United States	71457
13	Site 1073	New Bedford	Massachusetts	United States	02740
14	Site 1055	Detroit	Michigan	United States	48201
15	Site 1062	Detroit	Michigan	United States	48235
16	Site 1068	Royal Oak	Michigan	United States	48073
17	Site 1058	Saint Louis	Missouri	United States	63110
18	Site 1054	Butte	Montana	United States	59701
19	Site 1067	Lima	Ohio	United States	45801
20	Site 1056	Rapid City	South Dakota	United States	57702
21	1077	Hendersonville	Tennessee	United States
22	Site 1060	Houston	Texas	United States	77070
23	Site 1069	Houston	Texas	United States	77093
24	Site 1066	Splendora	Texas	United States	77372
25	Site 1059	Charlottesville	Virginia	United States	22908
26	Site 3059	Buenos Aires AV		Argentina
27	Site 3056	Ciudad Autónoma de Buenos Aires		Argentina
28	Site 3054	Cordoba		Argentina	X5000EPU
29	Site 3052	Cordoba		Argentina
30	Site 3057	Cordoba		Argentina
31	Site 3058	General Pacheco		Argentina
32	Site 3051	La Plata		Argentina
33	Site 3053	La Plata		Argentina
34	Site 3154	Belo Horizonte		Brazil	30150-221
35	Site 3153	Passo Fundo		Brazil	99010-080
36	Site 3152	Sao Jose do Rio Preto		Brazil	15090-000
37	4162	Ruse		Bulgaria	7002
38	Site 4154	Sliven		Bulgaria	8800
39	Site 4160	Sofia		Bulgaria	1233
40	Site 4157	Sofia		Bulgaria	1336
41	Site 4153	Sofia		Bulgaria	1606
42	Site 4156	Sofia		Bulgaria	1606
43	Site 4161	Sofia		Bulgaria	1680
44	4163	Sofia		Bulgaria
45	4164	Sofia		Bulgaria
46	4165	Sofia		Bulgaria
47	Site 4158	Stara Zagora		Bulgaria	6000
48	Site 4159	Vidin		Bulgaria	3700
49	Site 4152	Vratsa		Bulgaria	3000
50	Site 3353	Santiago		Chile
51	Site 3356	Santiago		Chile
52	Site 3357	Santiago		Chile
53	Site 3354	Talca		Chile
54	Site 3352	Temuco		Chile
55	Site 3355	Valdivia		Chile
56	Site 4256	Batumi		Georgia
57	Site 4253	Tbilisi		Georgia	101
58	Site 4255	Tbilisi		Georgia	159
59	Site 4252	Tbilisi		Georgia	179
60	Site 4254	Tbilisi		Georgia	186
61	Site 4354	Budapest		Hungary	1122
62	Site 4353	Budapest		Hungary	1134
63	Site 4352	Matrahaza		Hungary	3233
64	Site 4351	Torokbalint		Hungary	2045
65	Site 2254	Uijeongbu Si	Gyeonggi-do	Korea, Republic of	11765
66	Site 2257	Bucheon-si		Korea, Republic of	14647
67	Site 2253	Daegu		Korea, Republic of	42415
68	Site 2255	Seoul		Korea, Republic of	143-914
69	Site 2256	Seoul		Korea, Republic of	152-703
70	Site 2251	Seoul		Korea, Republic of	2259
71	Site 2252	Seoul		Korea, Republic of	7985
72	Site 4451	Liepāja		Latvia	LV3414
73	Site 4453	Rīga		Latvia	LV-1002
74	Site 4452	Valmiera		Latvia	LV 4201
75	Site 1153	Aguascalientes		Mexico	20230
76	Site 1154	Guadalajara		Mexico	44280
77	Site 1151	Monterrey		Mexico	64460
78	Site 1152	Toluca		Mexico	52140
79	Site 3264	Grau	Lima	Peru
80	Site 3262	Arequipa		Peru
81	Site 3263	Cusco		Peru
82	Site 3261	Cuzco		Peru
83	Site 3254	Ica		Peru
84	Site 3259	Iquitos		Peru
85	Site 3251	La Libertad		Peru
86	Site 3258	Lima Lima		Peru
87	Site 3252	Lima		Peru
88	Site 3253	Lima		Peru
89	Site 3255	Lima		Peru
90	Site 3257	Lima		Peru
91	Site 3260	Lima		Peru
92	Site 3265	Lima		Peru
93	Site 3256	Piura		Peru
94	Site 2053	Caloocan City		Philippines	1400
95	Site 2055	Cebu		Philippines	6000
96	Site 2052	Iloilo City		Philippines	5000
97	Site 2056	Quezon City		Philippines	1100
98	Site 2051	Quezon City		Philippines
99	Site 2054	Quezon		Philippines	1109
100	Site 4755	Bochnia		Poland	32-700
101	Site 4754	Chodziez		Poland	64-800
102	Site 4753	Krakow		Poland	31-011
103	Site 4756	Kraków		Poland	31-202
104	Site 4757	Siedlce		Poland	08-110
105	Site 4858	Bucuresti		Romania	21659
106	Site 4855	Bucureşti		Romania	21105
107	Site 4854	Bucureşti		Romania	30303
108	Site 4853	Cluj-Napoca		Romania	400371
109	Site 4851	Codlea		Romania	505100
110	Site 4857	Craiova		Romania	200515
111	Site 4856	Timisoara		Romania	300310
112	Site 4953	Barnaul		Russian Federation	656045
113	Site 4957	Moscow		Russian Federation	117913
114	Site 4952	Moscow		Russian Federation	119192
115	Site 4954	Novosibirsk		Russian Federation	6300
116	Site 4959	Saratov		Russian Federation	410053
117	Site 4958	Smolensk		Russian Federation	214019
118	Site 4955	St. Petersburg		Russian Federation	1962
119	Site 4951	St. Petersburg		Russian Federation	198205
120	Site 5052	Belgrade		Serbia	11000
121	Site 5056	Belgrade		Serbia	11000
122	Site 5051	Belgrade		Serbia	11080
123	5057	Belgrade		Serbia
124	Site 5055	Knez Selo		Serbia	1820
125	Site 5054	Kragujevac		Serbia	34000
126	Site 5053	Sremska Kamenica		Serbia	21204
127	Site 5151	Bloemfontein		South Africa	9301
128	Site 5154	Krugersdorp		South Africa	1739
129	Site 5155	Middelburg		South Africa	1050
130	Site 5156	Pretoria		South Africa
131	Site 5152	Queenswood		South Africa	186
132	Site 5153	Witbank		South Africa	1035
133	Site 4554	Alicante		Spain	3203
134	Site 4556	Badalona		Spain	8916
135	Site 4552	Barcelona		Spain	8003
136	Site 4555	Barcelona		Spain	8035
137	Site 4553	Madrid		Spain	28040
138	Site 4551	Madrid		Spain	28046
139	Site 2352	Kaohsiung		Taiwan	82445
140	Site 2351	Kaohsiung		Taiwan
141	Site 2354	Taipei		Taiwan
142	Site 5264	Chernivtsi		Ukraine	58001
143	Site 5261	Ivano-Frankivs'k		Ukraine	76018
144	Site 5258	Ivano-Frankivs'k		Ukraine	7601
145	Site 5256	Kharkiv		Ukraine	61124
146	Site 5254	Kharkiv		Ukraine	61157
147	Site 5255	Kherson		Ukraine	73000
148	Site 5263	Kyiv		Ukraine	1133
149	SIte 5252	Kyiv		Ukraine	2091
150	Site 5251	Kyiv		Ukraine	3680
151	Site 5265	Kyiv		Ukraine	3680
152	Site 5259	Poltava		Ukraine	3603
153	Site 5260	Vinnytsya		Ukraine	21029
154	Site 5253	Zaporizhzhya		Ukraine	69035
155	Site 5257	Zaporizhzhya		Ukraine	69065

Sponsors and Collaborators

• Nabriva Therapeutics AG

Investigators

• Study Chair: Leanne Gasink, MD, Nabriva Therapeutics AG

Study Documents (Full-Text)

• Statistical Analysis Plan - May 7, 2018
• Study Protocol - Mar 17, 2016

More Information

Publications

None provided.

• Responsible Party: Nabriva Therapeutics AG
• ClinicalTrials.gov Identifier: NCT02813694
• Other Study ID Numbers: NAB-BC-3781-3102
• First Posted: Jun 27, 2016
• Last Update Posted: Oct 23, 2019
• Last Verified: Sep 1, 2019

• Keywords provided by Nabriva Therapeutics AG: Pneumonia; CABP; CAP; Community acquired bacterial pneumonia
• Additional relevant MeSH terms: Pneumonia; Moxifloxacin; Lefamulin

Study Results

Participant Flow

Recruitment Details	The study was designed to enroll adults with CABP for which oral antibacterial therapy was appropriate. Subjects with PORT score of II, III and IV were eligible. The first subject was randomized in August 2016 and the last subject was randomized in December 2017
Pre-assignment Detail	Subjects who met inclusion criteria and did not meet exclusion criteria were randomly assigned to a treatment group. Administration of study drug was expected to occur as soon as possible after the diagnosis of CABP with all Screening/baseline assessments expected to be completed within 24 hours before the first dose of study drug.

Arm/Group Title	Lefamulin	Moxifloxacin
Arm/Group Description	oral lefamulin, 600mg	oral moxifloxacin, 400mg
Period Title: Overall Study
STARTED	370	368
COMPLETED	353	354
NOT COMPLETED	17	14

Baseline Characteristics

Arm/Group Title	Lefamulin	Moxifloxacin	Total
Arm/Group Description	oral lefamulin, 600mg	oral moxifloxacin, 400mg	Total of all reporting groups
Overall Participants	370	368	738
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	57.4 (16.4)	57.7 (16.2)	57.5 (16.3)
Sex: Female, Male (Count of Participants)
Female	163 44.1%	188 51.1%	351 47.6%
Male	207 55.9%	180 48.9%	387 52.4%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	45 12.2%	38 10.3%	83 11.2%
Not Hispanic or Latino	325 87.8%	330 89.7%	655 88.8%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	24 6.5%	17 4.6%	41 5.6%
Asian	49 13.2%	53 14.4%	102 13.8%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	19 5.1%	22 6%	41 5.6%
White	274 74.1%	270 73.4%	544 73.7%
More than one race	4 1.1%	6 1.6%	10 1.4%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
Argentina	6 1.6%	7 1.9%	13 1.8%
Romania	11 3%	7 1.9%	18 2.4%
Hungary	13 3.5%	15 4.1%	28 3.8%
United States	11 3%	12 3.3%	23 3.1%
Philippines	35 9.5%	36 9.8%	71 9.6%
Ukraine	65 17.6%	63 17.1%	128 17.3%
Russia	31 8.4%	24 6.5%	55 7.5%
Spain	0 0%	1 0.3%	1 0.1%
South Korea	12 3.2%	14 3.8%	26 3.5%
Latvia	3 0.8%	0 0%	3 0.4%
Taiwan	0 0%	1 0.3%	1 0.1%
Poland	4 1.1%	3 0.8%	7 0.9%
Mexico	1 0.3%	3 0.8%	4 0.5%
South Africa	21 5.7%	34 9.2%	55 7.5%
Georgia	22 5.9%	19 5.2%	41 5.6%
Bulgaria	38 10.3%	42 11.4%	80 10.8%
Chile	2 0.5%	2 0.5%	4 0.5%
Serbia	66 17.8%	63 17.1%	129 17.5%
Peru	29 7.8%	22 6%	51 6.9%
Renal Status (Count of Participants)
Severe impairment (CrCl <30 mL/min)	4 1.1%	3 0.8%	7 0.9%
Moderate impairment (CrCl 30 to <60 mL/min)	64 17.3%	70 19%	134 18.2%
Mild impairment (CrCl 60 to <90 mL/min)	112 30.3%	117 31.8%	229 31%
Normal function (CrCl >/= 90 mL/min)	190 51.4%	178 48.4%	368 49.9%
Pneumonia Outcomes Research Team (PORT) Risk Class (Count of Participants)
I	1 0.3%	2 0.5%	3 0.4%
II	183 49.5%	189 51.4%	372 50.4%
III	145 39.2%	133 36.1%	278 37.7%
IV	40 10.8%	42 11.4%	82 11.1%
V	1 0.3%	2 0.5%	3 0.4%
CURB-65 Score (Count of Participants)
0	87 23.5%	80 21.7%	167 22.6%
1	197 53.2%	196 53.3%	393 53.3%
2	74 20%	77 20.9%	151 20.5%
3	12 3.2%	13 3.5%	25 3.4%
4	0 0%	2 0.5%	2 0.3%
5	0 0%	0 0%	0 0%
American Thoracic Society (ATS) Minor Severity Criteria (Count of Participants)
Count of Participants [Participants]	31 8.4%	37 10.1%	68 9.2%
Systemic inflammatory response syndrome (SIRS) Criteria (Count of Participants)
Count of Participants [Participants]	353 95.4%	342 92.9%	695 94.2%
Bacteremic (Count of Participants)
Count of Participants [Participants]	6 1.6%	9 2.4%	15 2%
Received Single Dose Short-Acting Antibacterial within 72 hrs of Randomization (Count of Participants)
Count of Participants [Participants]	77 20.8%	72 19.6%	149 20.2%

Outcome Measures

1. Primary Outcome

Title	Early Clinical Response (ECR)
Description	ECR was defined as survival with improvement in at least 2 signs and symptoms of CABP (relative to baseline), no worsening of any CABP sign or symptom, and no use of concomitant antibiotics for the treatment of CABP through the ECR assessment
Time Frame	96 hours +/- 24 hours after first dose of study drug

Outcome Measure Data

Analysis Population Description

Intent to Treat Analysis Set: All randomized subjects

Arm/Group Title	Lefamulin	Moxifloxacin
Arm/Group Description	oral lefamulin, 600mg	oral moxifloxacin, 400mg
Measure Participants	370	368
Responder	336 90.8%	334 90.8%
Non-responder	29 7.8%	31 8.4%
Indeterminate	5 1.4%	3 0.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lefamulin, Moxifloxacin
	Comments
	Type of Statistical Test	Non-Inferiority
	Comments	non-inferiority margin= 10%
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	0.1
	Confidence Interval	(2-Sided) 95%; -4.4 to 4.5
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference in percentage of Responders for ECR (Lefamulin - Moxifloxacin). Confidence interval computed using continuity-corrected Z-statistic

2. Secondary Outcome

Title	Investigator's Assessment of Clinical Response (IACR)
Description	IACR was defined as resolution or improvement of a subject's clinical signs and symptoms such that no additional antibacterial therapy was administered for the treatment of the current episode of CABP
Time Frame	IACR was assessed at the Test-of-Cure Visit; 5 to 10 days after last dose of study drug

Outcome Measure Data

Analysis Population Description

Modified ITT population: All randomized subjects who received any amount of study drug

Arm/Group Title	Lefamulin	Moxifloxacin
Arm/Group Description	oral lefamulin, 600mg	oral moxifloxacin, 400mg
Measure Participants	368	368
Success	322 87%	328 89.1%
Failure	44 11.9%	32 8.7%
Indeterminate	2 0.5%	8 2.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lefamulin, Moxifloxacin
	Comments
	Type of Statistical Test	Non-Inferiority
	Comments	non-inferiority margin = 10%
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	-1.6
	Confidence Interval	(2-Sided) 95%; -6.3 to 3.1
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference in Percentage of Success for IACR at test of cure visit (Lefamulin - Moxifloxacin). CI computed via Miettinen-Nurminen method, adjusted for prior antibiotic use [Y vs. N] and PORT risk class [III vs. IV/V], using CMH stratum weights.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Lefamulin, Moxifloxacin
	Comments
	Type of Statistical Test	Non-Inferiority
	Comments	non-inferiority margain = 10%
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	-1.6
	Confidence Interval	(2-Sided) 95%; -6.5 to 3.3
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference in percentage of Success for IACR at test of cure visit. Confidence interval computed using a continuity-corrected Z-test.

3. Secondary Outcome

Title	Investigator's Assessment of Clinical Response (IACR)
Description	IACR was defined as resolution or improvement of a subject's clinical signs and symptoms such that no additional antibacterial therapy was administered for the treatment of the current episode of CABP
Time Frame	IACR was assessed at the Test-of-Cure Visit; 5 to 10 days after last dose of study drug

Outcome Measure Data

Analysis Population Description

Clinically Evaluable population: Subset of ITT population having met additional pre-defined criteria.

Arm/Group Title	Lefamulin	Moxifloxacin
Arm/Group Description	oral lefamulin, 600mg	oral moxifloxacin, 400mg
Measure Participants	330	326
Success	296 80%	305 82.9%
Failure	34 9.2%	21 5.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lefamulin, Moxifloxacin
	Comments
	Type of Statistical Test	Non-Inferiority
	Comments	non-inferiority margain = 10%
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	-3.9
	Confidence Interval	(2-Sided) 95%; -8.2 to 0.5
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference in percentage of success for IACR at test of cure visit (Lefamulin - Moxifloxacin). CI computed via Miettinen-Nurminen method, adjusted for prior antibiotic use [Y vs. N]; PORT risk class [III vs. IV/V], using CMH stratum weights.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Lefamulin, Moxifloxacin
	Comments
	Type of Statistical Test	Non-Inferiority
	Comments	non-inferiority margin = 10%
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	-3.9
	Confidence Interval	(2-Sided) 95%; -8.4 to 0.7
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference in Percentage of Success for IACR at test of cure visit (Lefamulin - Moxifloxacin). Confidence interval computed using continuity-corrected Z-statistic.

Adverse Events

Time Frame	Adverse events were recorded from the time of informed consent through the completion of the Test-of-Cure (TOC) Visit (i.e., 5-10 days after the last dose of study drug). Serious adverse events were recorded from the time of informed consent to the Late Follow-Up Visit (approximately 30 days after the first dose of study drug).
Adverse Event Reporting Description	Adverse events are reported for randomized subjects who received at least one dose of study drug (Safety Population). Treatment-emergent adverse events, defined as events occurring after the first dose of study drug, are reported. Adverse events were recorded whether or not they were considered to be study drug related.
Arm/Group Title	Lefamulin		Moxifloxacin
Arm/Group Description	oral lefamulin, 600mg		oral moxifloxacin, 400mg
All Cause Mortality
	Lefamulin		Moxifloxacin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/368 (1.4%)		3/368 (0.8%)
Serious Adverse Events
	Lefamulin		Moxifloxacin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	17/368 (4.6%)		18/368 (4.9%)
Blood and lymphatic system disorders
Anaemia	0/368 (0%)		1/368 (0.3%)
Cardiac disorders
Acute Myocardial Infarction	1/368 (0.3%)		2/368 (0.5%)
Atrial Fibrillation	1/368 (0.3%)		0/368 (0%)
Myocardial Infarction	1/368 (0.3%)		0/368 (0%)
Gastrointestinal disorders
Inguinal Hernia Strangulated	0/368 (0%)		1/368 (0.3%)
General disorders
Death	0/368 (0%)		1/368 (0.3%)
Hepatobiliary disorders
Cholecystitis Acute	0/368 (0%)		1/368 (0.3%)
Infections and infestations
Empyema	1/368 (0.3%)		0/368 (0%)
Endocarditis	1/368 (0.3%)		0/368 (0%)
Lung Abscess	1/368 (0.3%)		2/368 (0.5%)
Pneumonia	4/368 (1.1%)		1/368 (0.3%)
Pneumonia Bacterial	1/368 (0.3%)		0/368 (0%)
Tuberculous Pleurisy	0/368 (0%)		1/368 (0.3%)
Urinary Tract Infection	1/368 (0.3%)		1/368 (0.3%)
Investigations
Hepatic Enzyme Increased	0/368 (0%)		1/368 (0.3%)
Nuclear Magnetic Resonance Imaging Brain Abnormal	1/368 (0.3%)		0/368 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Acute Myeloid Leukaemia	1/368 (0.3%)		0/368 (0%)
Renal Cancer	1/368 (0.3%)		0/368 (0%)
Small Cell Lung Cancer	0/368 (0%)		1/368 (0.3%)
Squamous Cell Carcinoma of Lung	0/368 (0%)		1/368 (0.3%)
Nervous system disorders
Cerebral Infarction	0/368 (0%)		1/368 (0.3%)
Cerebrovascular Accident	0/368 (0%)		1/368 (0.3%)
Embolic Stroke	0/368 (0%)		1/368 (0.3%)
Respiratory, thoracic and mediastinal disorders
Acute Respiratory Distress Syndrome	2/368 (0.5%)		0/368 (0%)
Acute Respiratory Failure	1/368 (0.3%)		0/368 (0%)
Pulmonary Oedema	1/368 (0.3%)		0/368 (0%)
Respiratory Failure	0/368 (0%)		1/368 (0.3%)
Skin and subcutaneous tissue disorders
Angioedema	0/368 (0%)		1/368 (0.3%)
Other (Not Including Serious) Adverse Events
	Lefamulin		Moxifloxacin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	61/368 (16.6%)		12/368 (3.3%)
Gastrointestinal disorders
Diarrhoea	45/368 (12.2%)		4/368 (1.1%)
Nausea	19/368 (5.2%)		7/368 (1.9%)
Vomiting	12/368 (3.3%)		3/368 (0.8%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

All data from the study is confidential information. Sponsor has the right to publish first. Thereafter, PI may publish data from the study, but PI must submit the publication to Sponsor for review at least 60 days prior to publication. Sponsor may remove any confidential and/or proprietary information. If Sponsor's publication is not submitted within 12 months after the study, or if Sponsor decides not to publish, PI may publish the data, subject to Sponsor's rights in the agreement.