Trial Outcomes & Findings for Omadacycline vs Moxifloxacin for the Treatment of CABP (EudraCT #2013-004071-13) (NCT NCT02531438)

Last Updated: 2019-01-16

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

774 participants

Primary outcome timeframe

Screening; 72 to 120 hours after the first dose of test article

Results posted on

2019-01-16

Participant Flow

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.

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.

Participant milestones

Participant milestones
Measure	Omadacycline 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.	Moxifloxacin 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.
Overall Study STARTED	386	388
Overall Study COMPLETED	356	362
Overall Study NOT COMPLETED	30	26

Reasons for withdrawal

Reasons for withdrawal
Measure	Omadacycline 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.	Moxifloxacin 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.
Overall Study Adverse Event	7	9
Overall Study Lost to Follow-up	0	3
Overall Study Withdrawal by Subject	7	8
Overall Study Physician Decision	0	1
Overall Study Death	6	3
Overall Study Randomized, but Not Treated	4	0
Overall Study Missed EOT/PTE Visit	5	2
Overall Study Randomized with Exclusion Criteria	1	0

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Omadacycline n=386 Participants 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.	Moxifloxacin n=388 Participants 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 n=774 Participants Total of all reporting groups
Age, Customized 18 to 45 years old	62 Participants n=5 Participants	61 Participants n=7 Participants	123 Participants n=5 Participants
Age, Customized >45 to 65 years old	172 Participants n=5 Participants	155 Participants n=7 Participants	327 Participants n=5 Participants
Age, Customized >65 years old	152 Participants n=5 Participants	172 Participants n=7 Participants	324 Participants n=5 Participants
Age, Customized >75 years old	75 Participants n=5 Participants	83 Participants n=7 Participants	158 Participants n=5 Participants
Sex: Female, Male Female	178 Participants n=5 Participants	169 Participants n=7 Participants	347 Participants n=5 Participants
Sex: Female, Male Male	208 Participants n=5 Participants	219 Participants n=7 Participants	427 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) Asian	17 Participants n=5 Participants	18 Participants n=7 Participants	35 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	11 Participants n=5 Participants	7 Participants n=7 Participants	18 Participants n=5 Participants
Race (NIH/OMB) White	356 Participants n=5 Participants	355 Participants n=7 Participants	711 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	2 Participants n=5 Participants	6 Participants n=7 Participants	8 Participants n=5 Participants

PRIMARY outcome

Timeframe: Screening; 72 to 120 hours after the first dose of test article

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

Outcome measures

Outcome measures
Measure	Omadacycline n=386 Participants 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.	Moxifloxacin n=388 Participants 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.
Number of Participants With Early Clinical Response Clinical success	313 Participants	321 Participants
Number of Participants With Early Clinical Response Clinical failure	49 Participants	47 Participants
Number of Participants With Early Clinical Response Indeterminate	24 Participants	20 Participants

SECONDARY outcome

Timeframe: Screening; 5 to 10 days after the last day of therapy

Population: ITT Population

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.

Outcome measures

Outcome measures
Measure	Omadacycline n=386 Participants 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.	Moxifloxacin n=388 Participants 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.
Number of Participants With the Indicated Investigator Assessment of Clinical Response in the ITT Population at the Post Therapy Evaluation (PTE) Visit Indeterminate	16 Participants	16 Participants
Number of Participants With the Indicated Investigator Assessment of Clinical Response in the ITT Population at the Post Therapy Evaluation (PTE) Visit Clinical success	338 Participants	330 Participants
Number of Participants With the Indicated Investigator Assessment of Clinical Response in the ITT Population at the Post Therapy Evaluation (PTE) Visit Clinical failure	32 Participants	42 Participants

SECONDARY outcome

Timeframe: Screening; 5 to 10 days after the last day of therapy

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

Outcome measures

Outcome measures
Measure	Omadacycline n=340 Participants 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.	Moxifloxacin n=345 Participants 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.
Number of Participants With the Indicated Investigator Assessment of Clinical Response in the Clinically Evaluable-Post Therapy Evaluation (CT-PTE) Population Clinical success	316 Participants	312 Participants
Number of Participants With the Indicated Investigator Assessment of Clinical Response in the Clinically Evaluable-Post Therapy Evaluation (CT-PTE) Population Clinical failure	24 Participants	33 Participants

Adverse Events

Omadacycline

Serious events: 23 serious events

Other events: 63 other events

Deaths: 8 deaths

Moxifloxacin

Serious events: 26 serious events

Other events: 94 other events

Deaths: 4 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Omadacycline n=382 participants at risk 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.	Moxifloxacin n=388 participants at risk 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.
Gastrointestinal disorders Vomiting	2.6% 10/382 • 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 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.	1.5% 6/388 • 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 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.
Gastrointestinal disorders Constipation	2.4% 9/382 • 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 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.	1.5% 6/388 • 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 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.
Gastrointestinal disorders Nausea	2.4% 9/382 • 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 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.	5.4% 21/388 • 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 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.
Gastrointestinal disorders Diarrhea	1.0% 4/382 • 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 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.	8.0% 31/388 • 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 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.
Investigations Alanine aminotransferase increased	3.7% 14/382 • 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 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.	4.6% 18/388 • 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 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.
Investigations Gamma-glutamyl transferase increased	2.6% 10/382 • 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 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.	2.1% 8/388 • 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 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.
Investigations Aspartate aminotransferase increased	2.1% 8/382 • 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 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.	3.6% 14/388 • 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 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.
Nervous system disorders Headache	2.1% 8/382 • 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 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.	1.3% 5/388 • 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 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.
Psychiatric disorders Insomnia	2.6% 10/382 • 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 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.	2.1% 8/388 • 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 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.
Vascular disorders Hypertension	3.4% 13/382 • 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 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.	2.8% 11/388 • 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 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.

Additional Information

Dr. Paul McGovern; Vice President, Clinical Affairs

Paratek Pharmaceuticals, Inc.

Phone: 484-751-4935

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee 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.
Publication restrictions are in place

Restriction type: OTHER