Trial Outcomes & Findings for Efficacy and Safety of Levofloxacin for the Treatment of MDR-TB (NCT NCT01918397)

NCT ID: NCT01918397

Last Updated: 2023-05-24

Results Overview

The primary efficacy endpoint is the time to sputum culture conversion from positive to negative for M. tuberculosis growth on solid medium. This is defined as the time from initiation of study treatment to the first of two successive negative cultures one study visit apart that are not followed by a culture-positive specimen within 28 weeks of treatment initiation. To ensure that each subject will be evaluable for the primary endpoint, bi-weekly sputum cultures will be collected for 12 weeks, then every 4 weeks through 24 weeks of treatment.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

111 participants

Primary outcome timeframe

28 weeks

Results posted on

2023-05-24

Participant Flow

Participant milestones

Participant milestones
Measure	Dose 1 Levofloxacin 11mg/kg daily + Optimized Background Regimen (OBR) Levofloxacin: Levofloxacin is a quinolone antibiotic used to treat lung, sinus, skin, and urinary tract infections caused by bacteria. The chemical name is (-)-(S)-9fluoro-2,3-dihydro-3-methyl-10-(4-methyl-1-piperazinyl)-7-oxo-7H-pyrido\[1,2,3-de\]-1,4benzoxazine-6-carboxylic acid hemihydrate. Optimized background regimen (OBR): For this study "OBR" will mean optimized background regimen, not including a quinolone. OBR will be selected at the discretion of the study investigator to conform with standards of care and local site guidelines. In general, the OBR regimen should include at least 3 drugs (other than levofloxacin) to which the patient's isolate is not expected to be resistant, with one of these being an injectable agent, at the usual recommended doses.	Dose 2 Levofloxacin 14mg/kg daily + Optimized Background Regimen (OBR) Levofloxacin: Levofloxacin is a quinolone antibiotic used to treat lung, sinus, skin, and urinary tract infections caused by bacteria. The chemical name is (-)-(S)-9fluoro-2,3-dihydro-3-methyl-10-(4-methyl-1-piperazinyl)-7-oxo-7H-pyrido\[1,2,3-de\]-1,4benzoxazine-6-carboxylic acid hemihydrate. Optimized background regimen (OBR): For this study "OBR" will mean optimized background regimen, not including a quinolone. OBR will be selected at the discretion of the study investigator to conform with standards of care and local site guidelines. In general, the OBR regimen should include at least 3 drugs (other than levofloxacin) to which the patient's isolate is not expected to be resistant, with one of these being an injectable agent, at the usual recommended doses.	Dose 3 Levofloxacin 17mg/kg daily + Optimized Background Regimen (OBR) Levofloxacin: Levofloxacin is a quinolone antibiotic used to treat lung, sinus, skin, and urinary tract infections caused by bacteria. The chemical name is (-)-(S)-9fluoro-2,3-dihydro-3-methyl-10-(4-methyl-1-piperazinyl)-7-oxo-7H-pyrido\[1,2,3-de\]-1,4benzoxazine-6-carboxylic acid hemihydrate. Optimized background regimen (OBR): For this study "OBR" will mean optimized background regimen, not including a quinolone. OBR will be selected at the discretion of the study investigator to conform with standards of care and local site guidelines. In general, the OBR regimen should include at least 3 drugs (other than levofloxacin) to which the patient's isolate is not expected to be resistant, with one of these being an injectable agent, at the usual recommended doses.	Dose 4 Levofloxacin 20mg/kg daily + Optimized Background Regimen (OBR) Levofloxacin: Levofloxacin is a quinolone antibiotic used to treat lung, sinus, skin, and urinary tract infections caused by bacteria. The chemical name is (-)-(S)-9fluoro-2,3-dihydro-3-methyl-10-(4-methyl-1-piperazinyl)-7-oxo-7H-pyrido\[1,2,3-de\]-1,4benzoxazine-6-carboxylic acid hemihydrate. Optimized background regimen (OBR): For this study "OBR" will mean optimized background regimen, not including a quinolone. OBR will be selected at the discretion of the study investigator to conform with standards of care and local site guidelines. In general, the OBR regimen should include at least 3 drugs (other than levofloxacin) to which the patient's isolate is not expected to be resistant, with one of these being an injectable agent, at the usual recommended doses.
Overall Study STARTED	27	29	28	27
Overall Study COMPLETED	16	21	20	20
Overall Study NOT COMPLETED	11	8	8	7

Reasons for withdrawal

Reasons for withdrawal
Measure	Dose 1 Levofloxacin 11mg/kg daily + Optimized Background Regimen (OBR) Levofloxacin: Levofloxacin is a quinolone antibiotic used to treat lung, sinus, skin, and urinary tract infections caused by bacteria. The chemical name is (-)-(S)-9fluoro-2,3-dihydro-3-methyl-10-(4-methyl-1-piperazinyl)-7-oxo-7H-pyrido\[1,2,3-de\]-1,4benzoxazine-6-carboxylic acid hemihydrate. Optimized background regimen (OBR): For this study "OBR" will mean optimized background regimen, not including a quinolone. OBR will be selected at the discretion of the study investigator to conform with standards of care and local site guidelines. In general, the OBR regimen should include at least 3 drugs (other than levofloxacin) to which the patient's isolate is not expected to be resistant, with one of these being an injectable agent, at the usual recommended doses.	Dose 2 Levofloxacin 14mg/kg daily + Optimized Background Regimen (OBR) Levofloxacin: Levofloxacin is a quinolone antibiotic used to treat lung, sinus, skin, and urinary tract infections caused by bacteria. The chemical name is (-)-(S)-9fluoro-2,3-dihydro-3-methyl-10-(4-methyl-1-piperazinyl)-7-oxo-7H-pyrido\[1,2,3-de\]-1,4benzoxazine-6-carboxylic acid hemihydrate. Optimized background regimen (OBR): For this study "OBR" will mean optimized background regimen, not including a quinolone. OBR will be selected at the discretion of the study investigator to conform with standards of care and local site guidelines. In general, the OBR regimen should include at least 3 drugs (other than levofloxacin) to which the patient's isolate is not expected to be resistant, with one of these being an injectable agent, at the usual recommended doses.	Dose 3 Levofloxacin 17mg/kg daily + Optimized Background Regimen (OBR) Levofloxacin: Levofloxacin is a quinolone antibiotic used to treat lung, sinus, skin, and urinary tract infections caused by bacteria. The chemical name is (-)-(S)-9fluoro-2,3-dihydro-3-methyl-10-(4-methyl-1-piperazinyl)-7-oxo-7H-pyrido\[1,2,3-de\]-1,4benzoxazine-6-carboxylic acid hemihydrate. Optimized background regimen (OBR): For this study "OBR" will mean optimized background regimen, not including a quinolone. OBR will be selected at the discretion of the study investigator to conform with standards of care and local site guidelines. In general, the OBR regimen should include at least 3 drugs (other than levofloxacin) to which the patient's isolate is not expected to be resistant, with one of these being an injectable agent, at the usual recommended doses.	Dose 4 Levofloxacin 20mg/kg daily + Optimized Background Regimen (OBR) Levofloxacin: Levofloxacin is a quinolone antibiotic used to treat lung, sinus, skin, and urinary tract infections caused by bacteria. The chemical name is (-)-(S)-9fluoro-2,3-dihydro-3-methyl-10-(4-methyl-1-piperazinyl)-7-oxo-7H-pyrido\[1,2,3-de\]-1,4benzoxazine-6-carboxylic acid hemihydrate. Optimized background regimen (OBR): For this study "OBR" will mean optimized background regimen, not including a quinolone. OBR will be selected at the discretion of the study investigator to conform with standards of care and local site guidelines. In general, the OBR regimen should include at least 3 drugs (other than levofloxacin) to which the patient's isolate is not expected to be resistant, with one of these being an injectable agent, at the usual recommended doses.
Overall Study Never started treatment	2	1	0	0
Overall Study Adverse Event	1	1	1	0
Overall Study Lack of compliance	2	2	3	0
Overall Study Pregnancy	0	1	0	0
Overall Study Rifampin susceptible	0	0	0	2
Overall Study Treatment failure	0	0	0	1
Overall Study Withdrawal by Subject	3	2	1	1
Overall Study XDR at baseline	0	0	1	0
Overall Study Lost to Follow-up	2	1	1	1
Overall Study Increased QTc	1	0	0	1
Overall Study Death	0	0	1	0
Overall Study Involved in another investigative trial	0	0	0	1

Baseline Characteristics

Efficacy and Safety of Levofloxacin for the Treatment of MDR-TB

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Dose 1 n=27 Participants Levofloxacin 11mg/kg daily + Optimized Background Regimen (OBR) Levofloxacin: Levofloxacin is a quinolone antibiotic used to treat lung, sinus, skin, and urinary tract infections caused by bacteria. The chemical name is (-)-(S)-9fluoro-2,3-dihydro-3-methyl-10-(4-methyl-1-piperazinyl)-7-oxo-7H-pyrido\[1,2,3-de\]-1,4benzoxazine-6-carboxylic acid hemihydrate. Optimized background regimen (OBR): For this study "OBR" will mean optimized background regimen, not including a quinolone. OBR will be selected at the discretion of the study investigator to conform with standards of care and local site guidelines. In general, the OBR regimen should include at least 3 drugs (other than levofloxacin) to which the patient's isolate is not expected to be resistant, with one of these being an injectable agent, at the usual recommended doses.	Dose 2 n=29 Participants Levofloxacin 14mg/kg daily + Optimized Background Regimen (OBR) Levofloxacin: Levofloxacin is a quinolone antibiotic used to treat lung, sinus, skin, and urinary tract infections caused by bacteria. The chemical name is (-)-(S)-9fluoro-2,3-dihydro-3-methyl-10-(4-methyl-1-piperazinyl)-7-oxo-7H-pyrido\[1,2,3-de\]-1,4benzoxazine-6-carboxylic acid hemihydrate. Optimized background regimen (OBR): For this study "OBR" will mean optimized background regimen, not including a quinolone. OBR will be selected at the discretion of the study investigator to conform with standards of care and local site guidelines. In general, the OBR regimen should include at least 3 drugs (other than levofloxacin) to which the patient's isolate is not expected to be resistant, with one of these being an injectable agent, at the usual recommended doses.	Dose 3 n=28 Participants Levofloxacin 17mg/kg daily + Optimized Background Regimen (OBR) Levofloxacin: Levofloxacin is a quinolone antibiotic used to treat lung, sinus, skin, and urinary tract infections caused by bacteria. The chemical name is (-)-(S)-9fluoro-2,3-dihydro-3-methyl-10-(4-methyl-1-piperazinyl)-7-oxo-7H-pyrido\[1,2,3-de\]-1,4benzoxazine-6-carboxylic acid hemihydrate. Optimized background regimen (OBR): For this study "OBR" will mean optimized background regimen, not including a quinolone. OBR will be selected at the discretion of the study investigator to conform with standards of care and local site guidelines. In general, the OBR regimen should include at least 3 drugs (other than levofloxacin) to which the patient's isolate is not expected to be resistant, with one of these being an injectable agent, at the usual recommended doses.	Dose 4 n=27 Participants Levofloxacin 20mg/kg daily + Optimized Background Regimen (OBR) Levofloxacin: Levofloxacin is a quinolone antibiotic used to treat lung, sinus, skin, and urinary tract infections caused by bacteria. The chemical name is (-)-(S)-9fluoro-2,3-dihydro-3-methyl-10-(4-methyl-1-piperazinyl)-7-oxo-7H-pyrido\[1,2,3-de\]-1,4benzoxazine-6-carboxylic acid hemihydrate. Optimized background regimen (OBR): For this study "OBR" will mean optimized background regimen, not including a quinolone. OBR will be selected at the discretion of the study investigator to conform with standards of care and local site guidelines. In general, the OBR regimen should include at least 3 drugs (other than levofloxacin) to which the patient's isolate is not expected to be resistant, with one of these being an injectable agent, at the usual recommended doses.	Total n=111 Participants Total of all reporting groups
Age, Customized	32 years n=5 Participants	25 years n=7 Participants	26 years n=5 Participants	31 years n=4 Participants	26 years n=21 Participants
Sex: Female, Male Female	10 Participants n=5 Participants	9 Participants n=7 Participants	10 Participants n=5 Participants	14 Participants n=4 Participants	43 Participants n=21 Participants
Sex: Female, Male Male	17 Participants n=5 Participants	20 Participants n=7 Participants	18 Participants n=5 Participants	13 Participants n=4 Participants	68 Participants n=21 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	14 Participants n=5 Participants	17 Participants n=7 Participants	16 Participants n=5 Participants	15 Participants n=4 Participants	62 Participants n=21 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	12 Participants n=5 Participants	12 Participants n=7 Participants	12 Participants n=5 Participants	12 Participants n=4 Participants	48 Participants n=21 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants
Race/Ethnicity, Customized Black	5 Participants n=5 Participants	7 Participants n=7 Participants	6 Participants n=5 Participants	6 Participants n=4 Participants	24 Participants n=21 Participants
Race/Ethnicity, Customized Other	22 Participants n=5 Participants	22 Participants n=7 Participants	22 Participants n=5 Participants	21 Participants n=4 Participants	87 Participants n=21 Participants
Region of Enrollment South Africa	12 Participants n=5 Participants	12 Participants n=7 Participants	12 Participants n=5 Participants	12 Participants n=4 Participants	48 Participants n=21 Participants
Region of Enrollment Peru	15 Participants n=5 Participants	17 Participants n=7 Participants	16 Participants n=5 Participants	15 Participants n=4 Participants	63 Participants n=21 Participants

PRIMARY outcome

Timeframe: 28 weeks

Population: A modified intention to treat (MITT) population n=98 was analyzed.

Outcome measures

Outcome measures
Measure	Dose 1 n=24 Participants Levofloxacin 11mg/kg daily + Optimized Background Regimen (OBR) Levofloxacin: Levofloxacin is a quinolone antibiotic used to treat lung, sinus, skin, and urinary tract infections caused by bacteria. The chemical name is (-)-(S)-9fluoro-2,3-dihydro-3-methyl-10-(4-methyl-1-piperazinyl)-7-oxo-7H-pyrido\[1,2,3-de\]-1,4benzoxazine-6-carboxylic acid hemihydrate. Optimized background regimen (OBR): For this study "OBR" will mean optimized background regimen, not including a quinolone. OBR will be selected at the discretion of the study investigator to conform with standards of care and local site guidelines. In general, the OBR regimen should include at least 3 drugs (other than levofloxacin) to which the patient's isolate is not expected to be resistant, with one of these being an injectable agent, at the usual recommended doses.	Dose 2 n=27 Participants Levofloxacin 14mg/kg daily + Optimized Background Regimen (OBR) Levofloxacin: Levofloxacin is a quinolone antibiotic used to treat lung, sinus, skin, and urinary tract infections caused by bacteria. The chemical name is (-)-(S)-9fluoro-2,3-dihydro-3-methyl-10-(4-methyl-1-piperazinyl)-7-oxo-7H-pyrido\[1,2,3-de\]-1,4benzoxazine-6-carboxylic acid hemihydrate. Optimized background regimen (OBR): For this study "OBR" will mean optimized background regimen, not including a quinolone. OBR will be selected at the discretion of the study investigator to conform with standards of care and local site guidelines. In general, the OBR regimen should include at least 3 drugs (other than levofloxacin) to which the patient's isolate is not expected to be resistant, with one of these being an injectable agent, at the usual recommended doses.	Dose 3 n=24 Participants Levofloxacin 17mg/kg daily + Optimized Background Regimen (OBR) Levofloxacin: Levofloxacin is a quinolone antibiotic used to treat lung, sinus, skin, and urinary tract infections caused by bacteria. The chemical name is (-)-(S)-9fluoro-2,3-dihydro-3-methyl-10-(4-methyl-1-piperazinyl)-7-oxo-7H-pyrido\[1,2,3-de\]-1,4benzoxazine-6-carboxylic acid hemihydrate. Optimized background regimen (OBR): For this study "OBR" will mean optimized background regimen, not including a quinolone. OBR will be selected at the discretion of the study investigator to conform with standards of care and local site guidelines. In general, the OBR regimen should include at least 3 drugs (other than levofloxacin) to which the patient's isolate is not expected to be resistant, with one of these being an injectable agent, at the usual recommended doses.	Dose 4 n=23 Participants Levofloxacin 20mg/kg daily + Optimized Background Regimen (OBR) Levofloxacin: Levofloxacin is a quinolone antibiotic used to treat lung, sinus, skin, and urinary tract infections caused by bacteria. The chemical name is (-)-(S)-9fluoro-2,3-dihydro-3-methyl-10-(4-methyl-1-piperazinyl)-7-oxo-7H-pyrido\[1,2,3-de\]-1,4benzoxazine-6-carboxylic acid hemihydrate. Optimized background regimen (OBR): For this study "OBR" will mean optimized background regimen, not including a quinolone. OBR will be selected at the discretion of the study investigator to conform with standards of care and local site guidelines. In general, the OBR regimen should include at least 3 drugs (other than levofloxacin) to which the patient's isolate is not expected to be resistant, with one of these being an injectable agent, at the usual recommended doses.
Time to Sputum Culture Conversion	5.9 weeks Interval 2.3 to 10.1	6.3 weeks Interval 4.1 to 10.0	6.1 weeks Interval 4.1 to 10.1	6.1 weeks Interval 4.0 to 8.1

PRIMARY outcome

Timeframe: 28 weeks

Population: Intention to treat analysis based on the number of participants that completed treatment (n=108).

The primary safety endpoint will be the number of grade 3, 4 and 5 adverse events (AEs), occurring up to and including the time on study drug plus four weeks post study drug completion.

Outcome measures

Outcome measures
Measure	Dose 1 n=421 Events Levofloxacin 11mg/kg daily + Optimized Background Regimen (OBR) Levofloxacin: Levofloxacin is a quinolone antibiotic used to treat lung, sinus, skin, and urinary tract infections caused by bacteria. The chemical name is (-)-(S)-9fluoro-2,3-dihydro-3-methyl-10-(4-methyl-1-piperazinyl)-7-oxo-7H-pyrido\[1,2,3-de\]-1,4benzoxazine-6-carboxylic acid hemihydrate. Optimized background regimen (OBR): For this study "OBR" will mean optimized background regimen, not including a quinolone. OBR will be selected at the discretion of the study investigator to conform with standards of care and local site guidelines. In general, the OBR regimen should include at least 3 drugs (other than levofloxacin) to which the patient's isolate is not expected to be resistant, with one of these being an injectable agent, at the usual recommended doses.	Dose 2 n=419 Events Levofloxacin 14mg/kg daily + Optimized Background Regimen (OBR) Levofloxacin: Levofloxacin is a quinolone antibiotic used to treat lung, sinus, skin, and urinary tract infections caused by bacteria. The chemical name is (-)-(S)-9fluoro-2,3-dihydro-3-methyl-10-(4-methyl-1-piperazinyl)-7-oxo-7H-pyrido\[1,2,3-de\]-1,4benzoxazine-6-carboxylic acid hemihydrate. Optimized background regimen (OBR): For this study "OBR" will mean optimized background regimen, not including a quinolone. OBR will be selected at the discretion of the study investigator to conform with standards of care and local site guidelines. In general, the OBR regimen should include at least 3 drugs (other than levofloxacin) to which the patient's isolate is not expected to be resistant, with one of these being an injectable agent, at the usual recommended doses.	Dose 3 n=461 Events Levofloxacin 17mg/kg daily + Optimized Background Regimen (OBR) Levofloxacin: Levofloxacin is a quinolone antibiotic used to treat lung, sinus, skin, and urinary tract infections caused by bacteria. The chemical name is (-)-(S)-9fluoro-2,3-dihydro-3-methyl-10-(4-methyl-1-piperazinyl)-7-oxo-7H-pyrido\[1,2,3-de\]-1,4benzoxazine-6-carboxylic acid hemihydrate. Optimized background regimen (OBR): For this study "OBR" will mean optimized background regimen, not including a quinolone. OBR will be selected at the discretion of the study investigator to conform with standards of care and local site guidelines. In general, the OBR regimen should include at least 3 drugs (other than levofloxacin) to which the patient's isolate is not expected to be resistant, with one of these being an injectable agent, at the usual recommended doses.	Dose 4 n=519 Events Levofloxacin 20mg/kg daily + Optimized Background Regimen (OBR) Levofloxacin: Levofloxacin is a quinolone antibiotic used to treat lung, sinus, skin, and urinary tract infections caused by bacteria. The chemical name is (-)-(S)-9fluoro-2,3-dihydro-3-methyl-10-(4-methyl-1-piperazinyl)-7-oxo-7H-pyrido\[1,2,3-de\]-1,4benzoxazine-6-carboxylic acid hemihydrate. Optimized background regimen (OBR): For this study "OBR" will mean optimized background regimen, not including a quinolone. OBR will be selected at the discretion of the study investigator to conform with standards of care and local site guidelines. In general, the OBR regimen should include at least 3 drugs (other than levofloxacin) to which the patient's isolate is not expected to be resistant, with one of these being an injectable agent, at the usual recommended doses.
Number of Grade 3,4, and 5 AEs	5 Events	4 Events	14 Events	13 Events

SECONDARY outcome

Timeframe: 24 weeks

The primary endpoint for the analysis of tolerability will be the ability to complete 24 weeks of treatment with the assigned levofloxacin dose (in mg/kg at enrollment).

Outcome measures

Outcome measures
Measure	Dose 1 n=25 Participants Levofloxacin 11mg/kg daily + Optimized Background Regimen (OBR) Levofloxacin: Levofloxacin is a quinolone antibiotic used to treat lung, sinus, skin, and urinary tract infections caused by bacteria. The chemical name is (-)-(S)-9fluoro-2,3-dihydro-3-methyl-10-(4-methyl-1-piperazinyl)-7-oxo-7H-pyrido\[1,2,3-de\]-1,4benzoxazine-6-carboxylic acid hemihydrate. Optimized background regimen (OBR): For this study "OBR" will mean optimized background regimen, not including a quinolone. OBR will be selected at the discretion of the study investigator to conform with standards of care and local site guidelines. In general, the OBR regimen should include at least 3 drugs (other than levofloxacin) to which the patient's isolate is not expected to be resistant, with one of these being an injectable agent, at the usual recommended doses.	Dose 2 n=28 Participants Levofloxacin 14mg/kg daily + Optimized Background Regimen (OBR) Levofloxacin: Levofloxacin is a quinolone antibiotic used to treat lung, sinus, skin, and urinary tract infections caused by bacteria. The chemical name is (-)-(S)-9fluoro-2,3-dihydro-3-methyl-10-(4-methyl-1-piperazinyl)-7-oxo-7H-pyrido\[1,2,3-de\]-1,4benzoxazine-6-carboxylic acid hemihydrate. Optimized background regimen (OBR): For this study "OBR" will mean optimized background regimen, not including a quinolone. OBR will be selected at the discretion of the study investigator to conform with standards of care and local site guidelines. In general, the OBR regimen should include at least 3 drugs (other than levofloxacin) to which the patient's isolate is not expected to be resistant, with one of these being an injectable agent, at the usual recommended doses.	Dose 3 n=28 Participants Levofloxacin 17mg/kg daily + Optimized Background Regimen (OBR) Levofloxacin: Levofloxacin is a quinolone antibiotic used to treat lung, sinus, skin, and urinary tract infections caused by bacteria. The chemical name is (-)-(S)-9fluoro-2,3-dihydro-3-methyl-10-(4-methyl-1-piperazinyl)-7-oxo-7H-pyrido\[1,2,3-de\]-1,4benzoxazine-6-carboxylic acid hemihydrate. Optimized background regimen (OBR): For this study "OBR" will mean optimized background regimen, not including a quinolone. OBR will be selected at the discretion of the study investigator to conform with standards of care and local site guidelines. In general, the OBR regimen should include at least 3 drugs (other than levofloxacin) to which the patient's isolate is not expected to be resistant, with one of these being an injectable agent, at the usual recommended doses.	Dose 4 n=27 Participants Levofloxacin 20mg/kg daily + Optimized Background Regimen (OBR) Levofloxacin: Levofloxacin is a quinolone antibiotic used to treat lung, sinus, skin, and urinary tract infections caused by bacteria. The chemical name is (-)-(S)-9fluoro-2,3-dihydro-3-methyl-10-(4-methyl-1-piperazinyl)-7-oxo-7H-pyrido\[1,2,3-de\]-1,4benzoxazine-6-carboxylic acid hemihydrate. Optimized background regimen (OBR): For this study "OBR" will mean optimized background regimen, not including a quinolone. OBR will be selected at the discretion of the study investigator to conform with standards of care and local site guidelines. In general, the OBR regimen should include at least 3 drugs (other than levofloxacin) to which the patient's isolate is not expected to be resistant, with one of these being an injectable agent, at the usual recommended doses.
Number of Patients Completing Treatment	23 Participants	26 Participants	27 Participants	24 Participants

Adverse Events

Dose 1

Serious events: 2 serious events

Other events: 24 other events

Deaths: 0 deaths

Dose 2

Serious events: 1 serious events

Other events: 28 other events

Deaths: 0 deaths

Dose 3

Serious events: 4 serious events

Other events: 28 other events

Deaths: 1 deaths

Dose 4

Serious events: 3 serious events

Other events: 27 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Dose 1 n=25 participants at risk Levofloxacin 11mg/kg daily + Optimized Background Regimen (OBR) Levofloxacin: Levofloxacin is a quinolone antibiotic used to treat lung, sinus, skin, and urinary tract infections caused by bacteria. The chemical name is (-)-(S)-9fluoro-2,3-dihydro-3-methyl-10-(4-methyl-1-piperazinyl)-7-oxo-7H-pyrido\[1,2,3-de\]-1,4benzoxazine-6-carboxylic acid hemihydrate. Optimized background regimen (OBR): For this study "OBR" will mean optimized background regimen, not including a quinolone. OBR will be selected at the discretion of the study investigator to conform with standards of care and local site guidelines. In general, the OBR regimen should include at least 3 drugs (other than levofloxacin) to which the patient's isolate is not expected to be resistant, with one of these being an injectable agent, at the usual recommended doses.	Dose 2 n=28 participants at risk Levofloxacin 14mg/kg daily + Optimized Background Regimen (OBR) Levofloxacin: Levofloxacin is a quinolone antibiotic used to treat lung, sinus, skin, and urinary tract infections caused by bacteria. The chemical name is (-)-(S)-9fluoro-2,3-dihydro-3-methyl-10-(4-methyl-1-piperazinyl)-7-oxo-7H-pyrido\[1,2,3-de\]-1,4benzoxazine-6-carboxylic acid hemihydrate. Optimized background regimen (OBR): For this study "OBR" will mean optimized background regimen, not including a quinolone. OBR will be selected at the discretion of the study investigator to conform with standards of care and local site guidelines. In general, the OBR regimen should include at least 3 drugs (other than levofloxacin) to which the patient's isolate is not expected to be resistant, with one of these being an injectable agent, at the usual recommended doses.	Dose 3 n=28 participants at risk Levofloxacin 17mg/kg daily + Optimized Background Regimen (OBR) Levofloxacin: Levofloxacin is a quinolone antibiotic used to treat lung, sinus, skin, and urinary tract infections caused by bacteria. The chemical name is (-)-(S)-9fluoro-2,3-dihydro-3-methyl-10-(4-methyl-1-piperazinyl)-7-oxo-7H-pyrido\[1,2,3-de\]-1,4benzoxazine-6-carboxylic acid hemihydrate. Optimized background regimen (OBR): For this study "OBR" will mean optimized background regimen, not including a quinolone. OBR will be selected at the discretion of the study investigator to conform with standards of care and local site guidelines. In general, the OBR regimen should include at least 3 drugs (other than levofloxacin) to which the patient's isolate is not expected to be resistant, with one of these being an injectable agent, at the usual recommended doses.	Dose 4 n=27 participants at risk Levofloxacin 20mg/kg daily + Optimized Background Regimen (OBR) Levofloxacin: Levofloxacin is a quinolone antibiotic used to treat lung, sinus, skin, and urinary tract infections caused by bacteria. The chemical name is (-)-(S)-9fluoro-2,3-dihydro-3-methyl-10-(4-methyl-1-piperazinyl)-7-oxo-7H-pyrido\[1,2,3-de\]-1,4benzoxazine-6-carboxylic acid hemihydrate. Optimized background regimen (OBR): For this study "OBR" will mean optimized background regimen, not including a quinolone. OBR will be selected at the discretion of the study investigator to conform with standards of care and local site guidelines. In general, the OBR regimen should include at least 3 drugs (other than levofloxacin) to which the patient's isolate is not expected to be resistant, with one of these being an injectable agent, at the usual recommended doses.
Psychiatric disorders Acute psychosis	0.00% 0/25 • Adverse events were collected from the signing of consent form to the final visit. For a typical participant that would be 28 weeks. The definitions do not differ from the clinicaltrials.gov definitions.	3.6% 1/28 • Number of events 1 • Adverse events were collected from the signing of consent form to the final visit. For a typical participant that would be 28 weeks. The definitions do not differ from the clinicaltrials.gov definitions.	0.00% 0/28 • Adverse events were collected from the signing of consent form to the final visit. For a typical participant that would be 28 weeks. The definitions do not differ from the clinicaltrials.gov definitions.	0.00% 0/27 • Adverse events were collected from the signing of consent form to the final visit. For a typical participant that would be 28 weeks. The definitions do not differ from the clinicaltrials.gov definitions.
Respiratory, thoracic and mediastinal disorders Bronchospasm	4.0% 1/25 • Number of events 1 • Adverse events were collected from the signing of consent form to the final visit. For a typical participant that would be 28 weeks. The definitions do not differ from the clinicaltrials.gov definitions.	0.00% 0/28 • Adverse events were collected from the signing of consent form to the final visit. For a typical participant that would be 28 weeks. The definitions do not differ from the clinicaltrials.gov definitions.	0.00% 0/28 • Adverse events were collected from the signing of consent form to the final visit. For a typical participant that would be 28 weeks. The definitions do not differ from the clinicaltrials.gov definitions.	0.00% 0/27 • Adverse events were collected from the signing of consent form to the final visit. For a typical participant that would be 28 weeks. The definitions do not differ from the clinicaltrials.gov definitions.
Respiratory, thoracic and mediastinal disorders Chronic Obstructive Pulmonary disease	4.0% 1/25 • Number of events 1 • Adverse events were collected from the signing of consent form to the final visit. For a typical participant that would be 28 weeks. The definitions do not differ from the clinicaltrials.gov definitions.	0.00% 0/28 • Adverse events were collected from the signing of consent form to the final visit. For a typical participant that would be 28 weeks. The definitions do not differ from the clinicaltrials.gov definitions.	0.00% 0/28 • Adverse events were collected from the signing of consent form to the final visit. For a typical participant that would be 28 weeks. The definitions do not differ from the clinicaltrials.gov definitions.	0.00% 0/27 • Adverse events were collected from the signing of consent form to the final visit. For a typical participant that would be 28 weeks. The definitions do not differ from the clinicaltrials.gov definitions.
Psychiatric disorders Delirium	0.00% 0/25 • Adverse events were collected from the signing of consent form to the final visit. For a typical participant that would be 28 weeks. The definitions do not differ from the clinicaltrials.gov definitions.	0.00% 0/28 • Adverse events were collected from the signing of consent form to the final visit. For a typical participant that would be 28 weeks. The definitions do not differ from the clinicaltrials.gov definitions.	3.6% 1/28 • Number of events 1 • Adverse events were collected from the signing of consent form to the final visit. For a typical participant that would be 28 weeks. The definitions do not differ from the clinicaltrials.gov definitions.	0.00% 0/27 • Adverse events were collected from the signing of consent form to the final visit. For a typical participant that would be 28 weeks. The definitions do not differ from the clinicaltrials.gov definitions.
Infections and infestations Gastroenteritis	0.00% 0/25 • Adverse events were collected from the signing of consent form to the final visit. For a typical participant that would be 28 weeks. The definitions do not differ from the clinicaltrials.gov definitions.	0.00% 0/28 • Adverse events were collected from the signing of consent form to the final visit. For a typical participant that would be 28 weeks. The definitions do not differ from the clinicaltrials.gov definitions.	0.00% 0/28 • Adverse events were collected from the signing of consent form to the final visit. For a typical participant that would be 28 weeks. The definitions do not differ from the clinicaltrials.gov definitions.	3.7% 1/27 • Number of events 1 • Adverse events were collected from the signing of consent form to the final visit. For a typical participant that would be 28 weeks. The definitions do not differ from the clinicaltrials.gov definitions.
Hepatobiliary disorders Hepatic function abnormal	0.00% 0/25 • Adverse events were collected from the signing of consent form to the final visit. For a typical participant that would be 28 weeks. The definitions do not differ from the clinicaltrials.gov definitions.	0.00% 0/28 • Adverse events were collected from the signing of consent form to the final visit. For a typical participant that would be 28 weeks. The definitions do not differ from the clinicaltrials.gov definitions.	3.6% 1/28 • Number of events 1 • Adverse events were collected from the signing of consent form to the final visit. For a typical participant that would be 28 weeks. The definitions do not differ from the clinicaltrials.gov definitions.	0.00% 0/27 • Adverse events were collected from the signing of consent form to the final visit. For a typical participant that would be 28 weeks. The definitions do not differ from the clinicaltrials.gov definitions.
Immune system disorders Immune reconstitution inflammatory syndrome	0.00% 0/25 • Adverse events were collected from the signing of consent form to the final visit. For a typical participant that would be 28 weeks. The definitions do not differ from the clinicaltrials.gov definitions.	0.00% 0/28 • Adverse events were collected from the signing of consent form to the final visit. For a typical participant that would be 28 weeks. The definitions do not differ from the clinicaltrials.gov definitions.	3.6% 1/28 • Number of events 1 • Adverse events were collected from the signing of consent form to the final visit. For a typical participant that would be 28 weeks. The definitions do not differ from the clinicaltrials.gov definitions.	0.00% 0/27 • Adverse events were collected from the signing of consent form to the final visit. For a typical participant that would be 28 weeks. The definitions do not differ from the clinicaltrials.gov definitions.
Nervous system disorders Ischaemic Stroke	0.00% 0/25 • Adverse events were collected from the signing of consent form to the final visit. For a typical participant that would be 28 weeks. The definitions do not differ from the clinicaltrials.gov definitions.	0.00% 0/28 • Adverse events were collected from the signing of consent form to the final visit. For a typical participant that would be 28 weeks. The definitions do not differ from the clinicaltrials.gov definitions.	3.6% 1/28 • Number of events 1 • Adverse events were collected from the signing of consent form to the final visit. For a typical participant that would be 28 weeks. The definitions do not differ from the clinicaltrials.gov definitions.	0.00% 0/27 • Adverse events were collected from the signing of consent form to the final visit. For a typical participant that would be 28 weeks. The definitions do not differ from the clinicaltrials.gov definitions.
General disorders Oedema peripheral	0.00% 0/25 • Adverse events were collected from the signing of consent form to the final visit. For a typical participant that would be 28 weeks. The definitions do not differ from the clinicaltrials.gov definitions.	0.00% 0/28 • Adverse events were collected from the signing of consent form to the final visit. For a typical participant that would be 28 weeks. The definitions do not differ from the clinicaltrials.gov definitions.	0.00% 0/28 • Adverse events were collected from the signing of consent form to the final visit. For a typical participant that would be 28 weeks. The definitions do not differ from the clinicaltrials.gov definitions.	3.7% 1/27 • Number of events 1 • Adverse events were collected from the signing of consent form to the final visit. For a typical participant that would be 28 weeks. The definitions do not differ from the clinicaltrials.gov definitions.
Musculoskeletal and connective tissue disorders Pain in extremily	0.00% 0/25 • Adverse events were collected from the signing of consent form to the final visit. For a typical participant that would be 28 weeks. The definitions do not differ from the clinicaltrials.gov definitions.	0.00% 0/28 • Adverse events were collected from the signing of consent form to the final visit. For a typical participant that would be 28 weeks. The definitions do not differ from the clinicaltrials.gov definitions.	0.00% 0/28 • Adverse events were collected from the signing of consent form to the final visit. For a typical participant that would be 28 weeks. The definitions do not differ from the clinicaltrials.gov definitions.	3.7% 1/27 • Number of events 1 • Adverse events were collected from the signing of consent form to the final visit. For a typical participant that would be 28 weeks. The definitions do not differ from the clinicaltrials.gov definitions.
Respiratory, thoracic and mediastinal disorders Pneumothorax	0.00% 0/25 • Adverse events were collected from the signing of consent form to the final visit. For a typical participant that would be 28 weeks. The definitions do not differ from the clinicaltrials.gov definitions.	0.00% 0/28 • Adverse events were collected from the signing of consent form to the final visit. For a typical participant that would be 28 weeks. The definitions do not differ from the clinicaltrials.gov definitions.	0.00% 0/28 • Adverse events were collected from the signing of consent form to the final visit. For a typical participant that would be 28 weeks. The definitions do not differ from the clinicaltrials.gov definitions.	3.7% 1/27 • Number of events 1 • Adverse events were collected from the signing of consent form to the final visit. For a typical participant that would be 28 weeks. The definitions do not differ from the clinicaltrials.gov definitions.
Respiratory, thoracic and mediastinal disorders Pulmonary fistula	0.00% 0/25 • Adverse events were collected from the signing of consent form to the final visit. For a typical participant that would be 28 weeks. The definitions do not differ from the clinicaltrials.gov definitions.	0.00% 0/28 • Adverse events were collected from the signing of consent form to the final visit. For a typical participant that would be 28 weeks. The definitions do not differ from the clinicaltrials.gov definitions.	0.00% 0/28 • Adverse events were collected from the signing of consent form to the final visit. For a typical participant that would be 28 weeks. The definitions do not differ from the clinicaltrials.gov definitions.	3.7% 1/27 • Number of events 1 • Adverse events were collected from the signing of consent form to the final visit. For a typical participant that would be 28 weeks. The definitions do not differ from the clinicaltrials.gov definitions.
Investigations Weight decreased	0.00% 0/25 • Adverse events were collected from the signing of consent form to the final visit. For a typical participant that would be 28 weeks. The definitions do not differ from the clinicaltrials.gov definitions.	0.00% 0/28 • Adverse events were collected from the signing of consent form to the final visit. For a typical participant that would be 28 weeks. The definitions do not differ from the clinicaltrials.gov definitions.	3.6% 1/28 • Number of events 1 • Adverse events were collected from the signing of consent form to the final visit. For a typical participant that would be 28 weeks. The definitions do not differ from the clinicaltrials.gov definitions.	0.00% 0/27 • Adverse events were collected from the signing of consent form to the final visit. For a typical participant that would be 28 weeks. The definitions do not differ from the clinicaltrials.gov definitions.

Other adverse events

Additional Information

Charles R Horsburgh, MD

Boston University School of Public Health

Phone: 617-414-1282

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place