Omadacycline vs Moxifloxacin for the Treatment of CABP (EudraCT #2013-004071-13)

• Sponsor: Paratek Pharmaceuticals Inc (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02531438
• Collaborator: (none)
• Enrollment: 774
• Locations: 140
• Arms: 2
• Actual Duration (Months): 16.3
• Patients Per Site: 5.5
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the safety and efficacy of omadacycline as compared to moxifloxacin in the treatment of adults with community-acquired bacterial pneumonia.

Condition or Disease	Intervention/Treatment	Phase
Bacterial Pneumonia; Community-Acquired Infections	Drug: Omadacycline; Drug: Moxifloxacin	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 774 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase 3 Randomized, Double-Blind, Multi-Center Study to Compare the Safety and Efficacy of Omadacycline Intravenous (IV)/Oral (PO) to Moxifloxacin IV/PO for Treating Adults Subjects With Community-Acquired Bacterial Pneumonia
• Actual Study Start Date: Nov 1, 2015
• Actual Primary Completion Date: Feb 5, 2017
• Actual Study Completion Date: Mar 10, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Omadacycline Omadacycline IV; Omadacycline tablets	Drug: Omadacycline; Injection for IV; Oral tablets
Active Comparator: Moxifloxacin Moxifloxacin IV; Moxifloxacin tablets	Drug: Moxifloxacin; IV solution; Oral tablets; Other Names: Avelox

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Early Clinical Response [Screening; 72 to 120 hours after the first dose of test article]

   Early clinical response is defined as clinical success, categorized by survival with improvement of at least 1 level compared to Baseline in at least 2 CABP symptoms (cough, sputum production, pleuritic chest pain, and dyspnea) with no worsening in the other CABP symptoms. Response was determined programmatically using the investigator's assessment of the CABP symptoms. The severity of the participant's CABP symptoms was evaluated on a 4-point scale (absent, mild, moderate, or severe) based upon the CABP Subject Symptom Severity Guidance Framework for Investigator Assessment. An indeterminate response is defined as one that could not be adequately inferred because the participant was not assessed because they withdrew consent, were lost to follow-up, or other specified reason. Clinical failure is defined as no improvement by at least 1 level in CABP symptoms, worsening of any CABP symptom, alternative antibacterial treatment for CABP, discontinuation due to adverse event, or death.

Secondary Outcome Measures

1. Number of Participants With the Indicated Investigator Assessment of Clinical Response in the ITT Population at the Post Therapy Evaluation (PTE) Visit [Screening; 5 to 10 days after the last day of therapy]

   At the PTE Visit the investigator indicated one of the following outcomes relating to the primary infection under study: Clinical Success: survival after completion of a test article regimen without receiving any systemic antibacterial therapy other than test article, resolution of signs/symptoms of the infection present at Screening with no new symptoms/complications attributable to CABP and no need for further antibacterial therapy. Clinical Failure: alternative antibacterial treatment for CABP was required prior to the PTE Visit related to either (a) progression/development of new CABP symptoms or (b) development of infectious complications of CABP. Other reasons for clinical failure: participant received antibiotics that may have been effective for the infection under study for a different infection from the one under study; death prior to the PTE Visit. Indeterminate: the clinical response to test article could not be adequately inferred.

2. Number of Participants With the Indicated Investigator Assessment of Clinical Response in the Clinically Evaluable-Post Therapy Evaluation (CT-PTE) Population [Screening; 5 to 10 days after the last day of therapy]

   At the PTE Visit the investigator indicated one of the following outcomes relating to the primary infection under study: Clinical Success: survival after completion of a test article regimen without receiving any systemic antibacterial therapy other than test article, resolution of signs/symptoms of the infection present at Screening with no new symptoms/complications attributable to CABP and no need for further antibacterial therapy. Clinical Failure: alternative antibacterial treatment for CABP was required prior to the PTE Visit related to either (a) progression/development of new CABP symptoms or (b) development of infectious complications of CABP. Other reasons for clinical failure: participant received antibiotics that may have been effective for the infection under study for a different infection from the one under study; death prior to the PTE Visit.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Patients, ages 18 years or older who have signed the informed consent

• Has qualifying bacterial pneumonia

• Female patients must not be pregnant at the time of enrollment

• Must agree to a reliable method of birth control during the study and for 30 days following the last dose of study drug

Exclusion Criteria:

• Known or suspected hospital-acquired pneumonia

• Evidence of significant immunological disease

• Has a history of hypersensitivity or allergic reaction to any tetracycline or to any fluoroquinolone antibiotic

• Has received an investigational drug within past 30 days

• Women who are pregnant or nursing

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Site 514	Birmingham	Alabama	United States	35215
2	Site 501	Mobile	Alabama	United States	36608
3	Site 508	Laguna Hills	California	United States	92653
4	Site 505	Ventura	California	United States	93003
5	Site 513	Stamford	Connecticut	United States	06902
6	Site 511	Zachary	Louisiana	United States	70791
7	Site 503	Detroit	Michigan	United States	48202
8	Site 520	Saint Paul	Minnesota	United States	55101
9	Site 512	Saint Louis	Missouri	United States	63110
10	Site 506	Buffalo	New York	United States	14215
11	Site 509	Dayton	Ohio	United States	45409
12	Site 516	Huntington	West Virginia	United States	25701
13	Site 220	Liege		Belgium
14	Site 276	Belo Horizonte	Minas Gerais	Brazil
15	Site 277	Passo Fundo	Rio Grande Do Sul	Brazil
16	Site 274	Porto Alegre	Rio Grande Do Sul	Brazil
17	Site 279	São José Do Rio Preto	São Paulo	Brazil
18	Site 305	Kyustendil		Bulgaria
19	Site 303	Pernik		Bulgaria
20	Site 304	Plovdiv		Bulgaria
21	Site 306	Sliven		Bulgaria
22	Site 301	Sofia		Bulgaria
23	Site 302	Sofia		Bulgaria
24	Site 307	Sofia		Bulgaria
25	Site 250	Požega		Croatia
26	Site 205	Slavonski Brod		Croatia
27	Site 212	Zadar		Croatia
28	Site 201	Zagreb		Croatia
29	Site 202	Zagreb		Croatia
30	Site 203	Zagreb		Croatia
31	Site 251	Zagreb		Croatia
32	Site 405	Zagreb		Croatia
33	Site 412	Kyjov		Czechia
34	Site 411	Praha 10		Czechia
35	Site 410	Praha 5		Czechia
36	Site 414	Trebic		Czechia
37	Site 392	T'bilisi		Georgia
38	Site 390	Tbilisi		Georgia
39	Site 391	Tbilisi		Georgia
40	Site 393	Tbilisi		Georgia
41	Site 394	Tbilisi		Georgia
42	Site 415	Heidelberg		Germany
43	Site 416	Jena		Germany
44	Site 417	Paderborn		Germany
45	Site 207	Athens	Attika	Greece
46	Site 420	Athens	Attika	Greece
47	Site 210	Athens		Greece
48	Site 421	Athens		Greece
49	Site 208	Thessaloniki		Greece
50	Site 310	Budapest		Hungary
51	Site 311	Budapest		Hungary
52	Site 312	Budapest		Hungary
53	Site 314	Debrecen		Hungary
54	Site 316	Miskolc		Hungary
55	Site 313	Nyíregyháza		Hungary
56	Site 315	Szekesfehervar		Hungary
57	Site 213	Holon		Israel
58	Site 214	Nazareth		Israel
59	Site 217	Petach-Tikwa		Israel
60	Site 215	Ramat-Gan		Israel
61	Site 216	Safed		Israel
62	Site 293	Daegu		Korea, Republic of
63	Site 291	Seoul		Korea, Republic of
64	Site 292	Seoul		Korea, Republic of
65	Site 294	Seoul		Korea, Republic of
66	Site 322	Daugavpils		Latvia
67	Site 323	Liepaja		Latvia
68	Site 320	Riga		Latvia
69	Site 321	Riga		Latvia
70	Site 228	Guadalajara	Jalisco	Mexico
71	Site 472	Guadalajara	Jalisco	Mexico
72	Site 227	Monterrey	Nuevo Leon	Mexico
73	Site 471	Monterrey	Nuevo Leon	Mexico
74	Site 230	Xalapa	Veracruz	Mexico
75	Site 234	Cusco		Peru
76	Site 233	Lima		Peru
77	Site 236	Lima		Peru
78	Site 238	Lima		Peru
79	Site 239	Lima		Peru
80	Site 481	Lima		Peru
81	Site 237	Trujillo		Peru
82	Site 555	Caloocan City		Philippines
83	552	Iloilo City		Philippines
84	554	Manila City		Philippines
85	Site 551	Quezon City		Philippines
86	Site 553	Quezon City		Philippines
87	Site 332	Chrzanow		Poland
88	Site 333	Katowice		Poland
89	Site 334	Leczna		Poland
90	Site 331	Wroclaw		Poland
91	Site 330	Łódź		Poland
92	Site 344	Brasov		Romania
93	Site 340	Bucharest		Romania
94	Site 342	Bucharest		Romania
95	Site 343	Bucharest		Romania
96	Site 345	Craiova		Romania
97	Site 341	Timisoara		Romania
98	352	Moscow		Russian Federation
99	Site 350	Moscow		Russian Federation
100	Site 351	Moscow		Russian Federation
101	Site 353	Saint Petersburg		Russian Federation
102	Site 354	Saint Petersburg		Russian Federation
103	Site 355	Saint Petersburg		Russian Federation
104	Site 356	Saint Petersburg		Russian Federation
105	357	Sestroretsk		Russian Federation
106	Site 358	Vsevolozhsk		Russian Federation
107	Site 359	Zelenograd		Russian Federation
108	Site 431	Bratislava		Slovakia
109	Site 430	Levice		Slovakia
110	Site 432	Martin		Slovakia
111	Site 433	Nitra		Slovakia
112	Site 241	Benoni	Gauteng	South Africa
113	Site 436	Centurion	Gauteng	South Africa
114	Site 242	Pretoria	Guateng	South Africa
115	Site 244	Thabazimbi	Limpopo	South Africa
116	Site 245	Middelburg	Mpumalanga	South Africa
117	Site 437	Somerset West	Western Cape	South Africa
118	Site 225	Elche	Alicante	Spain
119	Site 221	Barcelona	Cataluña	Spain
120	Site 440	Barcelona	Cataluña	Spain
121	Site 224	Alcira	Valencia	Spain
122	Site 226	Alicante		Spain
123	Site 299	Kaohsiung		Taiwan
124	Site 297	Tainan		Taiwan
125	Site 295	Taipei		Taiwan
126	Site 296	Taipei		Taiwan
127	Site 298	Taipei		Taiwan
128	Site 247	Ankara		Turkey
129	Site 248	Ankara		Turkey
130	Site 249	Ankara		Turkey
131	Site 246	Trabzon		Turkey
132	Site 380	Dnipropetrovs'k		Ukraine
133	Site 373	Dnipropetrovsk		Ukraine
134	Site 374	Kharkiv		Ukraine
135	Site 375	Kharkiv		Ukraine
136	Site 370	Kyiv		Ukraine
137	Site 372	Kyiv		Ukraine
138	Site 378	Kyiv		Ukraine
139	Site 379	Kyiv		Ukraine
140	Site 376	Zaporizhia		Ukraine

Sponsors and Collaborators

• Paratek Pharmaceuticals Inc

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Mar 17, 2017

More Information

Publications

None provided.

• Responsible Party: Paratek Pharmaceuticals Inc
• ClinicalTrials.gov Identifier: NCT02531438
• Other Study ID Numbers: PTK0796-CABP-1200
• First Posted: Aug 24, 2015
• Last Update Posted: Jan 16, 2019
• Last Verified: Jan 1, 2019

• Additional relevant MeSH terms: Pneumonia; Pneumonia, Bacterial; Community-Acquired Infections; Moxifloxacin

Study Results

Participant Flow

Recruitment Details	Participant randomization was stratified by Pneumonia Outcomes Research Team (PORT) Risk Class (II or III/IV), receipt of an allowed antibacterial therapy in the 72 hours prior to study treatment, and geographic region. All participants were expected to present with CABP severe enough to require at least 3 days of intravenous (IV) treatment.
Pre-assignment Detail	Participants who met inclusion criteria and did not meet exclusion criteria were randomly assigned to a treatment group, and received their first dose of test article within 4 hours after randomization. All participants were expected to present with CABP PORT Risk Class II, III, or IV to require a minimum of at least 3 days of IV treatment.

Arm/Group Title	Omadacycline	Moxifloxacin
Arm/Group Description	Participants received omadacycline 100 milligrams (mg) intravenously (IV) every 12 hours (q12h) (first 2 doses), followed by 100 mg IV every 24 hours (q24h) (starting 24 hours after the first dose), with the option to switch to a 300 mg (two 150 mg omadacycline tablets and 1 over-encapsulated placebo tablet matching moxifloxacin) oral administration q24h after at least 3 days (4 doses) of IV treatment. The total duration of test article therapy (IV plus oral administration) for all participants was at least 7 days and no more than 14 days.	Participants received moxifloxacin 400 mg IV q24h (with a single placebo infusion to match the omadacycline dosing regimen 12 hours after the first dose on Day 1) with the option to switch to a 400 mg (one 400 mg moxifloxacin over-encapsulated tablet and 2 placebo tablets matching omadacycline tablets) oral administration q24h after at least 3 days (4 doses) of IV treatment. The total duration of test article therapy (IV plus oral administration) for all participants was at least 7 days and no more than 14 days.
Period Title: Overall Study
STARTED	386	388
COMPLETED	356	362
NOT COMPLETED	30	26

Baseline Characteristics

Arm/Group Title	Omadacycline	Moxifloxacin	Total
Arm/Group Description	Participants received omadacycline 100 milligrams (mg) intravenously (IV) every 12 hours (q12h) (first 2 doses), followed by 100 mg IV every 24 hours (q24h) (starting 24 hours after the first dose), with the option to switch to a 300 mg (two 150 mg omadacycline tablets and 1 over-encapsulated placebo tablet matching moxifloxacin) oral administration q24h after at least 3 days (4 doses) of IV treatment. The total duration of test article therapy (IV plus oral administration) for all participants was at least 7 days and no more than 14 days.	Participants received moxifloxacin 400 mg IV q24h (with a single placebo infusion to match the omadacycline dosing regimen 12 hours after the first dose on Day 1) with the option to switch to a 400 mg (one 400 mg moxifloxacin over-encapsulated tablet and 2 placebo tablets matching omadacycline tablets) oral administration q24h after at least 3 days (4 doses) of IV treatment. The total duration of test article therapy (IV plus oral administration) for all participants was at least 7 days and no more than 14 days.	Total of all reporting groups
Overall Participants	386	388	774
Age, Customized (Count of Participants)
18 to 45 years old	62 16.1%	61 15.7%	123 15.9%
>45 to 65 years old	172 44.6%	155 39.9%	327 42.2%
>65 years old	152 39.4%	172 44.3%	324 41.9%
>75 years old	75 19.4%	83 21.4%	158 20.4%
Sex: Female, Male (Count of Participants)
Female	178 46.1%	169 43.6%	347 44.8%
Male	208 53.9%	219 56.4%	427 55.2%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	2 0.5%	2 0.3%
Asian	17 4.4%	18 4.6%	35 4.5%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	11 2.8%	7 1.8%	18 2.3%
White	356 92.2%	355 91.5%	711 91.9%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	2 0.5%	6 1.5%	8 1%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Early Clinical Response
Description	Early clinical response is defined as clinical success, categorized by survival with improvement of at least 1 level compared to Baseline in at least 2 CABP symptoms (cough, sputum production, pleuritic chest pain, and dyspnea) with no worsening in the other CABP symptoms. Response was determined programmatically using the investigator's assessment of the CABP symptoms. The severity of the participant's CABP symptoms was evaluated on a 4-point scale (absent, mild, moderate, or severe) based upon the CABP Subject Symptom Severity Guidance Framework for Investigator Assessment. An indeterminate response is defined as one that could not be adequately inferred because the participant was not assessed because they withdrew consent, were lost to follow-up, or other specified reason. Clinical failure is defined as no improvement by at least 1 level in CABP symptoms, worsening of any CABP symptom, alternative antibacterial treatment for CABP, discontinuation due to adverse event, or death.
Time Frame	Screening; 72 to 120 hours after the first dose of test article

Outcome Measure Data

Analysis Population Description

Intent-to-Treat (ITT) Population: all randomized participants regardless of whether or not the participant received the test article

Arm/Group Title	Omadacycline	Moxifloxacin
Arm/Group Description	Participants received omadacycline 100 milligrams (mg) intravenously (IV) every 12 hours (q12h) (first 2 doses), followed by 100 mg IV every 24 hours (q24h) (starting 24 hours after the first dose), with the option to switch to a 300 mg (two 150 mg omadacycline tablets and 1 over-encapsulated placebo tablet matching moxifloxacin) oral administration q24h after at least 3 days (4 doses) of IV treatment. The total duration of test article therapy (IV plus oral administration) for all participants was at least 7 days and no more than 14 days.	Participants received moxifloxacin 400 mg IV q24h (with a single placebo infusion to match the omadacycline dosing regimen 12 hours after the first dose on Day 1) with the option to switch to a 400 mg (one 400 mg moxifloxacin over-encapsulated tablet and 2 placebo tablets matching omadacycline tablets) oral administration q24h after at least 3 days (4 doses) of IV treatment. The total duration of test article therapy (IV plus oral administration) for all participants was at least 7 days and no more than 14 days.
Measure Participants	386	388
Clinical success	313 81.1%	321 82.7%
Clinical failure	49 12.7%	47 12.1%
Indeterminate	24 6.2%	20 5.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Omadacycline, Moxifloxacin
	Comments
	Type of Statistical Test	Non-Inferiority
	Comments	A non-inferiority margin of 10% was used for the analysis.
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%; -7.1 to 3.8
	Parameter Dispersion	Type: Value:
	Estimation Comments	The 95% confidence interval was constructed based on the Miettinen and Nurminen method without stratification. Treatment difference for a response of clinical success was calculated as omadacycline minus moxifloxacin.

2. Secondary Outcome

Title	Number of Participants With the Indicated Investigator Assessment of Clinical Response in the ITT Population at the Post Therapy Evaluation (PTE) Visit
Description	At the PTE Visit the investigator indicated one of the following outcomes relating to the primary infection under study: Clinical Success: survival after completion of a test article regimen without receiving any systemic antibacterial therapy other than test article, resolution of signs/symptoms of the infection present at Screening with no new symptoms/complications attributable to CABP and no need for further antibacterial therapy. Clinical Failure: alternative antibacterial treatment for CABP was required prior to the PTE Visit related to either (a) progression/development of new CABP symptoms or (b) development of infectious complications of CABP. Other reasons for clinical failure: participant received antibiotics that may have been effective for the infection under study for a different infection from the one under study; death prior to the PTE Visit. Indeterminate: the clinical response to test article could not be adequately inferred.
Time Frame	Screening; 5 to 10 days after the last day of therapy

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	Omadacycline	Moxifloxacin
Arm/Group Description	Participants received omadacycline 100 milligrams (mg) intravenously (IV) every 12 hours (q12h) (first 2 doses), followed by 100 mg IV every 24 hours (q24h) (starting 24 hours after the first dose), with the option to switch to a 300 mg (two 150 mg omadacycline tablets and 1 over-encapsulated placebo tablet matching moxifloxacin) oral administration q24h after at least 3 days (4 doses) of IV treatment. The total duration of test article therapy (IV plus oral administration) for all participants was at least 7 days and no more than 14 days.	Participants received moxifloxacin 400 mg IV q24h (with a single placebo infusion to match the omadacycline dosing regimen 12 hours after the first dose on Day 1) with the option to switch to a 400 mg (one 400 mg moxifloxacin over-encapsulated tablet and 2 placebo tablets matching omadacycline tablets) oral administration q24h after at least 3 days (4 doses) of IV treatment. The total duration of test article therapy (IV plus oral administration) for all participants was at least 7 days and no more than 14 days.
Measure Participants	386	388
Clinical success	338 87.6%	330 85.1%
Clinical failure	32 8.3%	42 10.8%
Indeterminate	16 4.1%	16 4.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Omadacycline, Moxifloxacin
	Comments
	Type of Statistical Test	Non-Inferiority
	Comments	A non-inferiority margin of 10% was used for the analysis.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	treatment difference
	Estimated Value	2.5
	Confidence Interval	(2-Sided) 95%; -2.4 to 7.4
	Parameter Dispersion	Type: Value:
	Estimation Comments	The 95% confidence interval was constructed based on the Miettinen and Nurminen method without stratification. Treatment difference for a response of clinical success was calculated as omadacycline minus moxifloxacin.

3. Secondary Outcome

Title	Number of Participants With the Indicated Investigator Assessment of Clinical Response in the Clinically Evaluable-Post Therapy Evaluation (CT-PTE) Population
Description	At the PTE Visit the investigator indicated one of the following outcomes relating to the primary infection under study: Clinical Success: survival after completion of a test article regimen without receiving any systemic antibacterial therapy other than test article, resolution of signs/symptoms of the infection present at Screening with no new symptoms/complications attributable to CABP and no need for further antibacterial therapy. Clinical Failure: alternative antibacterial treatment for CABP was required prior to the PTE Visit related to either (a) progression/development of new CABP symptoms or (b) development of infectious complications of CABP. Other reasons for clinical failure: participant received antibiotics that may have been effective for the infection under study for a different infection from the one under study; death prior to the PTE Visit.
Time Frame	Screening; 5 to 10 days after the last day of therapy

Outcome Measure Data

Analysis Population Description

CE-PTE Population: all participants in the ITT Population meeting additional pre-defined criteria

Arm/Group Title	Omadacycline	Moxifloxacin
Arm/Group Description	Participants received omadacycline 100 milligrams (mg) intravenously (IV) every 12 hours (q12h) (first 2 doses), followed by 100 mg IV every 24 hours (q24h) (starting 24 hours after the first dose), with the option to switch to a 300 mg (two 150 mg omadacycline tablets and 1 over-encapsulated placebo tablet matching moxifloxacin) oral administration q24h after at least 3 days (4 doses) of IV treatment. The total duration of test article therapy (IV plus oral administration) for all participants was at least 7 days and no more than 14 days.	Participants received moxifloxacin 400 mg IV q24h (with a single placebo infusion to match the omadacycline dosing regimen 12 hours after the first dose on Day 1) with the option to switch to a 400 mg (one 400 mg moxifloxacin over-encapsulated tablet and 2 placebo tablets matching omadacycline tablets) oral administration q24h after at least 3 days (4 doses) of IV treatment. The total duration of test article therapy (IV plus oral administration) for all participants was at least 7 days and no more than 14 days.
Measure Participants	340	345
Clinical success	316 81.9%	312 80.4%
Clinical failure	24 6.2%	33 8.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Omadacycline, Moxifloxacin
	Comments
	Type of Statistical Test	Non-Inferiority
	Comments	A non-inferiority margin of 10% was used for the analysis.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	treatment difference
	Estimated Value	2.5
	Confidence Interval	(2-Sided) 95%; -1.7 to 6.8
	Parameter Dispersion	Type: Value:
	Estimation Comments	The 95% confidence interval was constructed based on the Miettinen and Nurminen method without stratification. Treatment difference for a response of clinical success was calculated as omadacycline minus moxifloxacin.

Adverse Events

Time Frame	Adverse events were assessed from the signing of Informed Consent Form to the time of the Final Follow-up assessment (up to 30 to 37 days after the start of the first infusion of test article)
Adverse Event Reporting Description	Adverse events are reported for members of the Safety Population, comprised of all randomized participants who received test article (either active or placebo). Treatment-emergent adverse events, defined as events occurring after the first dose of active test article, are reported.
Arm/Group Title	Omadacycline		Moxifloxacin
Arm/Group Description	Participants received omadacycline 100 milligrams (mg) intravenously (IV) every 12 hours (q12h) (first 2 doses), followed by 100 mg IV every 24 hours (q24h) (starting 24 hours after the first dose), with the option to switch to a 300 mg (two 150 mg omadacycline tablets and 1 over-encapsulated placebo tablet matching moxifloxacin) oral administration q24h after at least 3 days (4 doses) of IV treatment. The total duration of test article therapy (IV plus oral administration) for all participants was at least 7 days and no more than 14 days.		Participants received moxifloxacin 400 mg IV q24h (with a single placebo infusion to match the omadacycline dosing regimen 12 hours after the first dose on Day 1) with the option to switch to a 400 mg (one 400 mg moxifloxacin over-encapsulated tablet and 2 placebo tablets matching omadacycline tablets) oral administration q24h after at least 3 days (4 doses) of IV treatment. The total duration of test article therapy (IV plus oral administration) for all participants was at least 7 days and no more than 14 days.
All Cause Mortality
	Omadacycline		Moxifloxacin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	8/382 (2.1%)		4/388 (1%)
Serious Adverse Events
	Omadacycline		Moxifloxacin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	23/382 (6%)		26/388 (6.7%)
Cardiac disorders
Acute Myocardial Infarction	2/382 (0.5%)		0/388 (0%)
Cardiogenic Shock	2/382 (0.5%)		1/388 (0.3%)
Cardiac Arrest	1/382 (0.3%)		0/388 (0%)
Cardiac Failure	1/382 (0.3%)		1/388 (0.3%)
Cardio-Respiratory Arrest	1/382 (0.3%)		0/388 (0%)
Tachycardia	1/382 (0.3%)		0/388 (0%)
Pericardial Effusion	0/382 (0%)		1/388 (0.3%)
Right Ventricular Failure	0/382 (0%)		1/388 (0.3%)
Gastrointestinal disorders
Colitis	0/382 (0%)		1/388 (0.3%)
General disorders
Multi-Organ Failure	1/382 (0.3%)		0/388 (0%)
Hepatobiliary disorders
Cholecystitis Acute	1/382 (0.3%)		0/388 (0%)
Hepatic Failure	1/382 (0.3%)		0/388 (0%)
Hepatic Congestion	0/382 (0%)		1/388 (0.3%)
Infections and infestations
Influenza	3/382 (0.8%)		0/388 (0%)
Pneumonia	2/382 (0.5%)		6/388 (1.5%)
Cellulitis	1/382 (0.3%)		0/388 (0%)
Infectious Pleural Effusion	1/382 (0.3%)		1/388 (0.3%)
Septic Shock	1/382 (0.3%)		2/388 (0.5%)
Atypical Mycobacterial Pneumonia	0/382 (0%)		1/388 (0.3%)
Clostridium Difficile Colitis	0/382 (0%)		1/388 (0.3%)
Clostridium Difficile Infection	0/382 (0%)		2/388 (0.5%)
human Immunodeficiency Virus (HIV) Infection	0/382 (0%)		1/388 (0.3%)
Infective Exacerbation Of Bronchiectasis	0/382 (0%)		1/388 (0.3%)
Lung Abscess	0/382 (0%)		1/388 (0.3%)
Pneumonia Viral	0/382 (0%)		1/388 (0.3%)
Injury, poisoning and procedural complications
Bladder Injury	0/382 (0%)		1/388 (0.3%)
Metabolism and nutrition disorders
Decreased Appetite	1/382 (0.3%)		0/388 (0%)
Musculoskeletal and connective tissue disorders
Back Pain	1/382 (0.3%)		0/388 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lung Neoplasm	2/382 (0.5%)		2/388 (0.5%)
Adenocarcinoma	0/382 (0%)		1/388 (0.3%)
Chronic Lymphocytic Leukaemia	0/382 (0%)		1/388 (0.3%)
Colon Cancer Metastatic	0/382 (0%)		1/388 (0.3%)
Pancreatic Carcinoma	0/382 (0%)		1/388 (0.3%)
Nervous system disorders
Cerebrovascular Accident	2/382 (0.5%)		0/388 (0%)
Psychiatric disorders
Anxiety	1/382 (0.3%)		0/388 (0%)
Renal and urinary disorders
Renal Failure Acute	0/382 (0%)		2/388 (0.5%)
Respiratory, thoracic and mediastinal disorders
Pleural Effusion	3/382 (0.8%)		0/388 (0%)
Acute Respiratory Distress Syndrome	2/382 (0.5%)		0/388 (0%)
Acute Respiratory Failure	2/382 (0.5%)		3/388 (0.8%)
Acute Pulmonary Oedema	1/382 (0.3%)		0/388 (0%)
Vascular disorders
Aortic Aneurysm Rupture	1/382 (0.3%)		0/388 (0%)
Peripheral Ischaemia	0/382 (0%)		1/388 (0.3%)
Other (Not Including Serious) Adverse Events
	Omadacycline		Moxifloxacin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	63/382 (16.5%)		94/388 (24.2%)
Gastrointestinal disorders
Vomiting	10/382 (2.6%)		6/388 (1.5%)
Constipation	9/382 (2.4%)		6/388 (1.5%)
Nausea	9/382 (2.4%)		21/388 (5.4%)
Diarrhea	4/382 (1%)		31/388 (8%)
Investigations
Alanine aminotransferase increased	14/382 (3.7%)		18/388 (4.6%)
Gamma-glutamyl transferase increased	10/382 (2.6%)		8/388 (2.1%)
Aspartate aminotransferase increased	8/382 (2.1%)		14/388 (3.6%)
Nervous system disorders
Headache	8/382 (2.1%)		5/388 (1.3%)
Psychiatric disorders
Insomnia	10/382 (2.6%)		8/388 (2.1%)
Vascular disorders
Hypertension	13/382 (3.4%)		11/388 (2.8%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The only disclosure restriction on the Principal Investigator is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days from the time submitted to the sponsor for review. The sponsor can request changes to the communication and require the removal of confidential information.