Trial Outcomes & Findings for Single-dose Study in Two Panels of Healthy Adult Participants to Assess Immediate-Release and Dispersible Formulations of Pretomanid (NCT NCT04309656)

NCT ID: NCT04309656

Last Updated: 2024-07-24

Results Overview

Relative bioavailability will be determined separately for each panel using Cmax

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

48 participants

Primary outcome timeframe

intake (pre-dose), and at 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72, and 96 hours post dose

Results posted on

2024-07-24

Participant Flow

Participant milestones

Participant milestones
Measure	Panel 1: Pretomanid After Meal Each participant will receive four single-dose treatments. Panel 1 will receive a required FDA standard high fat, high-calorie meal before dosing. Pretomanid: 1) Treatment A (reference) = 200 mg given as a single 200 mg tablet (using the immediate release formulation), orally administered. 2\) Treatment B (test) = 200 mg given as four 50-mg tablets (using the dispersible pediatric formulation), orally administered. 3\) Treatment C (test) = single 50-mg dispersible tablet, orally administered. 4) Treatment D (test) = single 10-mg dispersible tablet, orally administered.	Panel 2: Pretomanid After Fast Each participant will receive four single-dose treatments. Panel 2 will fast before dosing. Pretomanid: 1) Treatment A (reference) = 200 mg given as a single 200 mg tablet (using the immediate release formulation), orally administered. 2\) Treatment B (test) = 200 mg given as four 50-mg tablets (using the dispersible pediatric formulation), orally administered. 3\) Treatment C (test) = single 50-mg dispersible tablet, orally administered. 4) Treatment D (test) = single 10-mg dispersible tablet, orally administered.
Overall Study STARTED	24	24
Overall Study COMPLETED	24	24
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Single-dose Study in Two Panels of Healthy Adult Participants to Assess Immediate-Release and Dispersible Formulations of Pretomanid

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Panel 1: Pretomanid After Meal n=24 Participants Each participant will receive four single-dose treatments. Panel 1 will receive a required FDA standard high fat, high-calorie meal before dosing.	Panel 2: Pretomanid After Fast n=24 Participants Each participant will receive four single-dose treatments. Panel 2 will fast before dosing.	Total n=48 Participants Total of all reporting groups
Age, Continuous	37.7 years STANDARD_DEVIATION 8.5 • n=5 Participants	36.4 years STANDARD_DEVIATION 7.2 • n=7 Participants	37.0 years STANDARD_DEVIATION 7.82 • n=5 Participants
Sex: Female, Male Female	8 Participants n=5 Participants	8 Participants n=7 Participants	16 Participants n=5 Participants
Sex: Female, Male Male	16 Participants n=5 Participants	16 Participants n=7 Participants	32 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	13 Participants n=5 Participants	8 Participants n=7 Participants	21 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	11 Participants n=5 Participants	16 Participants n=7 Participants	27 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Black or African American	8 Participants n=5 Participants	15 Participants n=7 Participants	23 Participants n=5 Participants
Race (NIH/OMB) White	14 Participants n=5 Participants	9 Participants n=7 Participants	23 Participants n=5 Participants
Race (NIH/OMB) More than one race	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Height at Screening	170.70 centimeter STANDARD_DEVIATION 7.962 • n=5 Participants	170.96 centimeter STANDARD_DEVIATION 11.953 • n=7 Participants	170.83 centimeter STANDARD_DEVIATION 10.048 • n=5 Participants
Weight at Screening	79.06 kilogram STANDARD_DEVIATION 11.601 • n=5 Participants	78.49 kilogram STANDARD_DEVIATION 13.633 • n=7 Participants	78.77 kilogram STANDARD_DEVIATION 12.526 • n=5 Participants
BMI at Screening	27.08 kilogram per meter squared STANDARD_DEVIATION 2.882 • n=5 Participants	26.76 kilogram per meter squared STANDARD_DEVIATION 2.996 • n=7 Participants	26.92 kilogram per meter squared STANDARD_DEVIATION 2.913 • n=5 Participants

PRIMARY outcome

Timeframe: intake (pre-dose), and at 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72, and 96 hours post dose

Population: Quantifiable predose concentrations that were below 5% of the respective Cmax values were included in the pharmacokinetic analyses without adjustment. Data for subjects with quantifiable predose concentrations that were above 5% of the respective Cmax values were excluded from concentration-time descriptive statistics and mean concentration-time profiles

Relative bioavailability will be determined separately for each panel using Cmax

Outcome measures

Outcome measures
Measure	Treatment D Fed and Fasted Each participant will receive four single-dose treatments in both fed and fasted conditions Pretomanid: 1) Treatment D(reference) = 200 mg given as a single 200 mg tablet (using the immediate release formulation), orally administered.	Treatment A Fed and Fasted n=24 Participants Each participant will receive four single-dose treatments in both fed and fasted conditions. Treatment A (reference) = 200 mg pretomanid given as a single 200 mg tablet (using the immediate release formulation), orally administered	Treatment B Fed and Fasted n=24 Participants Each participant will receive four single-dose treatments in both fed and fasted conditions Treatment B (test) = 200 mg given as four 50-mg tablets (using the dispersible pediatric formulation), orally administered.	Treatment C Fed and Fasted Each participant will receive four single-dose treatments in both fed and fasted conditions Treatment C (test) = single 50-mg dispersible tablet, orally administered.	Panel 2:Treatment A Each participant received four single-dose treatments. Panel 2 fasted before dosing. Pretomanid: 1) Treatment A (reference) = 200 mg given as a single 200 mg tablet (using the immediate release formulation), orally administered. 2\) Treatment B (test) = 200 mg given as four 50-mg tablets (using the dispersible pediatric formulation), orally administered. 3\) Treatment C (test) = single 50-mg dispersible tablet, orally administered. 4) Treatment D (test) = single 10-mg dispersible tablet, orally administered	Panel 2: Treatment B Each participant received four single-dose treatments. Panel 2 fasted before dosing. Pretomanid: 1) Treatment A (reference) = 200 mg given as a single 200 mg tablet (using the immediate release formulation), orally administered. 2\) Treatment B (test) = 200 mg given as four 50-mg tablets (using the dispersible pediatric formulation), orally administered. 3\) Treatment C (test) = single 50-mg dispersible tablet, orally administered. 4) Treatment D (test) = single 10-mg dispersible tablet, orally administered	Panel 2: Treatment C Each participant received four single-dose treatments. Panel 2 fasted before dosing. Pretomanid: 1) Treatment A (reference) = 200 mg given as a single 200 mg tablet (using the immediate release formulation), orally administered. 2\) Treatment B (test) = 200 mg given as four 50-mg tablets (using the dispersible pediatric formulation), orally administered. 3\) Treatment C (test) = single 50-mg dispersible tablet, orally administered. 4) Treatment D (test) = single 10-mg dispersible tablet, orally administered	Panel 2: Treatment D Each participant received four single-dose treatments. Panel 2 fasted before dosing. Pretomanid: 1) Treatment A (reference) = 200 mg given as a single 200 mg tablet (using the immediate release formulation), orally administered. 2\) Treatment B (test) = 200 mg given as four 50-mg tablets (using the dispersible pediatric formulation), orally administered. 3\) Treatment C (test) = single 50-mg dispersible tablet, orally administered. 4) Treatment D (test) = single 10-mg dispersible tablet, orally administered
Relative Bioavailability - Cmax Treatment A	—	2170 ng/mL Standard Deviation 484	1180 ng/mL Standard Deviation 401	—	—	—	—	—
Relative Bioavailability - Cmax Treatment B	—	1850 ng/mL Standard Deviation 354	1090 ng/mL Standard Deviation 334	—	—	—	—	—
Relative Bioavailability - Cmax Treatment C	—	389 ng/mL Standard Deviation 58.8	427 ng/mL Standard Deviation 111	—	—	—	—	—
Relative Bioavailability - Cmax Treatment D	—	76.7 ng/mL Standard Deviation 14.2	110 ng/mL Standard Deviation 20.2	—	—	—	—	—

PRIMARY outcome

Timeframe: intake (pre-dose), and at 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72, and 96 hours post dose

Relative bioavailability will be determined separately for each panel using AUC 0-t (area under the time vs concentration curve from time 0 to time t : h\*ng/mL)

Outcome measures

Outcome measures
Measure	Treatment D Fed and Fasted Each participant will receive four single-dose treatments in both fed and fasted conditions Pretomanid: 1) Treatment D(reference) = 200 mg given as a single 200 mg tablet (using the immediate release formulation), orally administered.	Treatment A Fed and Fasted n=24 Participants Each participant will receive four single-dose treatments in both fed and fasted conditions. Treatment A (reference) = 200 mg pretomanid given as a single 200 mg tablet (using the immediate release formulation), orally administered	Treatment B Fed and Fasted n=24 Participants Each participant will receive four single-dose treatments in both fed and fasted conditions Treatment B (test) = 200 mg given as four 50-mg tablets (using the dispersible pediatric formulation), orally administered.	Treatment C Fed and Fasted Each participant will receive four single-dose treatments in both fed and fasted conditions Treatment C (test) = single 50-mg dispersible tablet, orally administered.	Panel 2:Treatment A Each participant received four single-dose treatments. Panel 2 fasted before dosing. Pretomanid: 1) Treatment A (reference) = 200 mg given as a single 200 mg tablet (using the immediate release formulation), orally administered. 2\) Treatment B (test) = 200 mg given as four 50-mg tablets (using the dispersible pediatric formulation), orally administered. 3\) Treatment C (test) = single 50-mg dispersible tablet, orally administered. 4) Treatment D (test) = single 10-mg dispersible tablet, orally administered	Panel 2: Treatment B Each participant received four single-dose treatments. Panel 2 fasted before dosing. Pretomanid: 1) Treatment A (reference) = 200 mg given as a single 200 mg tablet (using the immediate release formulation), orally administered. 2\) Treatment B (test) = 200 mg given as four 50-mg tablets (using the dispersible pediatric formulation), orally administered. 3\) Treatment C (test) = single 50-mg dispersible tablet, orally administered. 4) Treatment D (test) = single 10-mg dispersible tablet, orally administered	Panel 2: Treatment C Each participant received four single-dose treatments. Panel 2 fasted before dosing. Pretomanid: 1) Treatment A (reference) = 200 mg given as a single 200 mg tablet (using the immediate release formulation), orally administered. 2\) Treatment B (test) = 200 mg given as four 50-mg tablets (using the dispersible pediatric formulation), orally administered. 3\) Treatment C (test) = single 50-mg dispersible tablet, orally administered. 4) Treatment D (test) = single 10-mg dispersible tablet, orally administered	Panel 2: Treatment D Each participant received four single-dose treatments. Panel 2 fasted before dosing. Pretomanid: 1) Treatment A (reference) = 200 mg given as a single 200 mg tablet (using the immediate release formulation), orally administered. 2\) Treatment B (test) = 200 mg given as four 50-mg tablets (using the dispersible pediatric formulation), orally administered. 3\) Treatment C (test) = single 50-mg dispersible tablet, orally administered. 4) Treatment D (test) = single 10-mg dispersible tablet, orally administered
Relative Bioavailability - AUC 0-t Treatment A	—	54900 h*ng/mL Standard Deviation 10700	32900 h*ng/mL Standard Deviation 7580	—	—	—	—	—
Relative Bioavailability - AUC 0-t Treatment B	—	55200 h*ng/mL Standard Deviation 10800	30200 h*ng/mL Standard Deviation 9030	—	—	—	—	—
Relative Bioavailability - AUC 0-t Treatment C	—	12300 h*ng/mL Standard Deviation 2790	10900 h*ng/mL Standard Deviation 3150	—	—	—	—	—
Relative Bioavailability - AUC 0-t Treatment D	—	2040 h*ng/mL Standard Deviation 514	2460 h*ng/mL Standard Deviation 513	—	—	—	—	—

PRIMARY outcome

Timeframe: intake (pre-dose), and at 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72, and 96 hours post dose

Relative bioavailability will be determined separately for each panel using AUC 0-inf (area under the time vs concentration curve from time 0 to infinite time)

Outcome measures

Outcome measures
Measure	Treatment D Fed and Fasted Each participant will receive four single-dose treatments in both fed and fasted conditions Pretomanid: 1) Treatment D(reference) = 200 mg given as a single 200 mg tablet (using the immediate release formulation), orally administered.	Treatment A Fed and Fasted n=24 Participants Each participant will receive four single-dose treatments in both fed and fasted conditions. Treatment A (reference) = 200 mg pretomanid given as a single 200 mg tablet (using the immediate release formulation), orally administered	Treatment B Fed and Fasted n=24 Participants Each participant will receive four single-dose treatments in both fed and fasted conditions Treatment B (test) = 200 mg given as four 50-mg tablets (using the dispersible pediatric formulation), orally administered.	Treatment C Fed and Fasted Each participant will receive four single-dose treatments in both fed and fasted conditions Treatment C (test) = single 50-mg dispersible tablet, orally administered.	Panel 2:Treatment A Each participant received four single-dose treatments. Panel 2 fasted before dosing. Pretomanid: 1) Treatment A (reference) = 200 mg given as a single 200 mg tablet (using the immediate release formulation), orally administered. 2\) Treatment B (test) = 200 mg given as four 50-mg tablets (using the dispersible pediatric formulation), orally administered. 3\) Treatment C (test) = single 50-mg dispersible tablet, orally administered. 4) Treatment D (test) = single 10-mg dispersible tablet, orally administered	Panel 2: Treatment B Each participant received four single-dose treatments. Panel 2 fasted before dosing. Pretomanid: 1) Treatment A (reference) = 200 mg given as a single 200 mg tablet (using the immediate release formulation), orally administered. 2\) Treatment B (test) = 200 mg given as four 50-mg tablets (using the dispersible pediatric formulation), orally administered. 3\) Treatment C (test) = single 50-mg dispersible tablet, orally administered. 4) Treatment D (test) = single 10-mg dispersible tablet, orally administered	Panel 2: Treatment C Each participant received four single-dose treatments. Panel 2 fasted before dosing. Pretomanid: 1) Treatment A (reference) = 200 mg given as a single 200 mg tablet (using the immediate release formulation), orally administered. 2\) Treatment B (test) = 200 mg given as four 50-mg tablets (using the dispersible pediatric formulation), orally administered. 3\) Treatment C (test) = single 50-mg dispersible tablet, orally administered. 4) Treatment D (test) = single 10-mg dispersible tablet, orally administered	Panel 2: Treatment D Each participant received four single-dose treatments. Panel 2 fasted before dosing. Pretomanid: 1) Treatment A (reference) = 200 mg given as a single 200 mg tablet (using the immediate release formulation), orally administered. 2\) Treatment B (test) = 200 mg given as four 50-mg tablets (using the dispersible pediatric formulation), orally administered. 3\) Treatment C (test) = single 50-mg dispersible tablet, orally administered. 4) Treatment D (test) = single 10-mg dispersible tablet, orally administered
Relative Bioavailability - AUC 0-inf Treatment A	—	57400 h*ng/mL Standard Deviation 12300	34700 h*ng/mL Standard Deviation 8330	—	—	—	—	—
Relative Bioavailability - AUC 0-inf Treatment B	—	57900 h*ng/mL Standard Deviation 12400	31900 h*ng/mL Standard Deviation 10200	—	—	—	—	—
Relative Bioavailability - AUC 0-inf Treatment C	—	12700 h*ng/mL Standard Deviation 3210	11400 h*ng/mL Standard Deviation 3440	—	—	—	—	—
Relative Bioavailability - AUC 0-inf Treatment D	—	2100 h*ng/mL Standard Deviation 552	2530 h*ng/mL Standard Deviation 551	—	—	—	—	—

SECONDARY outcome

Timeframe: intake (pre-dose), and at 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72, and 96 hours post dose

Population: Ratio(%) = Geometric Mean (Test)/Geometric Mean (Ref). Quantifiable predose concentrations that were below 5% of the respective Cmax values were included in the pharmacokinetic analyses without adjustment. Data for subjects with quantifiable predose concentrations that were above 5% of the respective Cmax values were excluded from concentration-time descriptive statistics and mean concentration-time profiles

Food effect on bioavailability will be determined across panels using Cmax. Reported in Ratio(%) of the Geometric Mean (Fed)/Geometric Mean (Fasted) based on Least Squares Mean of log-transformed parameter values (ng/mL)

Outcome measures

Outcome measures
Measure	Treatment D Fed and Fasted n=34 Participants Each participant will receive four single-dose treatments in both fed and fasted conditions Pretomanid: 1) Treatment D(reference) = 200 mg given as a single 200 mg tablet (using the immediate release formulation), orally administered.	Treatment A Fed and Fasted n=48 Participants Each participant will receive four single-dose treatments in both fed and fasted conditions. Treatment A (reference) = 200 mg pretomanid given as a single 200 mg tablet (using the immediate release formulation), orally administered	Treatment B Fed and Fasted n=48 Participants Each participant will receive four single-dose treatments in both fed and fasted conditions Treatment B (test) = 200 mg given as four 50-mg tablets (using the dispersible pediatric formulation), orally administered.	Treatment C Fed and Fasted n=46 Participants Each participant will receive four single-dose treatments in both fed and fasted conditions Treatment C (test) = single 50-mg dispersible tablet, orally administered.	Panel 2:Treatment A Each participant received four single-dose treatments. Panel 2 fasted before dosing. Pretomanid: 1) Treatment A (reference) = 200 mg given as a single 200 mg tablet (using the immediate release formulation), orally administered. 2\) Treatment B (test) = 200 mg given as four 50-mg tablets (using the dispersible pediatric formulation), orally administered. 3\) Treatment C (test) = single 50-mg dispersible tablet, orally administered. 4) Treatment D (test) = single 10-mg dispersible tablet, orally administered	Panel 2: Treatment B Each participant received four single-dose treatments. Panel 2 fasted before dosing. Pretomanid: 1) Treatment A (reference) = 200 mg given as a single 200 mg tablet (using the immediate release formulation), orally administered. 2\) Treatment B (test) = 200 mg given as four 50-mg tablets (using the dispersible pediatric formulation), orally administered. 3\) Treatment C (test) = single 50-mg dispersible tablet, orally administered. 4) Treatment D (test) = single 10-mg dispersible tablet, orally administered	Panel 2: Treatment C Each participant received four single-dose treatments. Panel 2 fasted before dosing. Pretomanid: 1) Treatment A (reference) = 200 mg given as a single 200 mg tablet (using the immediate release formulation), orally administered. 2\) Treatment B (test) = 200 mg given as four 50-mg tablets (using the dispersible pediatric formulation), orally administered. 3\) Treatment C (test) = single 50-mg dispersible tablet, orally administered. 4) Treatment D (test) = single 10-mg dispersible tablet, orally administered	Panel 2: Treatment D Each participant received four single-dose treatments. Panel 2 fasted before dosing. Pretomanid: 1) Treatment A (reference) = 200 mg given as a single 200 mg tablet (using the immediate release formulation), orally administered. 2\) Treatment B (test) = 200 mg given as four 50-mg tablets (using the dispersible pediatric formulation), orally administered. 3\) Treatment C (test) = single 50-mg dispersible tablet, orally administered. 4) Treatment D (test) = single 10-mg dispersible tablet, orally administered
Food Effect - Ratio of Cmax Fed Vs Fasted	69.38 Ratio (%) Interval 61.96 to 77.68	187.65 Ratio (%) Interval 165.9 to 212.25	173.24 Ratio (%) Interval 153.26 to 195.82	93.25 Ratio (%) Interval 83.16 to 104.56	—	—	—	—

SECONDARY outcome

Timeframe: intake (pre-dose), and at 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72, and 96 hours post dose

Food effect on bioavailability was assessed across panels based on the 90% confidence intervals (CIs) for estimates of the geometric mean ratios between AUC 0-t of fed versus fasted across panels. An analysis of variance was used for each treatment with panel as the fixed effect.

Outcome measures

Outcome measures
Measure	Treatment D Fed and Fasted n=34 Participants Each participant will receive four single-dose treatments in both fed and fasted conditions Pretomanid: 1) Treatment D(reference) = 200 mg given as a single 200 mg tablet (using the immediate release formulation), orally administered.	Treatment A Fed and Fasted n=48 Participants Each participant will receive four single-dose treatments in both fed and fasted conditions. Treatment A (reference) = 200 mg pretomanid given as a single 200 mg tablet (using the immediate release formulation), orally administered	Treatment B Fed and Fasted n=48 Participants Each participant will receive four single-dose treatments in both fed and fasted conditions Treatment B (test) = 200 mg given as four 50-mg tablets (using the dispersible pediatric formulation), orally administered.	Treatment C Fed and Fasted n=46 Participants Each participant will receive four single-dose treatments in both fed and fasted conditions Treatment C (test) = single 50-mg dispersible tablet, orally administered.	Panel 2:Treatment A Each participant received four single-dose treatments. Panel 2 fasted before dosing. Pretomanid: 1) Treatment A (reference) = 200 mg given as a single 200 mg tablet (using the immediate release formulation), orally administered. 2\) Treatment B (test) = 200 mg given as four 50-mg tablets (using the dispersible pediatric formulation), orally administered. 3\) Treatment C (test) = single 50-mg dispersible tablet, orally administered. 4) Treatment D (test) = single 10-mg dispersible tablet, orally administered	Panel 2: Treatment B Each participant received four single-dose treatments. Panel 2 fasted before dosing. Pretomanid: 1) Treatment A (reference) = 200 mg given as a single 200 mg tablet (using the immediate release formulation), orally administered. 2\) Treatment B (test) = 200 mg given as four 50-mg tablets (using the dispersible pediatric formulation), orally administered. 3\) Treatment C (test) = single 50-mg dispersible tablet, orally administered. 4) Treatment D (test) = single 10-mg dispersible tablet, orally administered	Panel 2: Treatment C Each participant received four single-dose treatments. Panel 2 fasted before dosing. Pretomanid: 1) Treatment A (reference) = 200 mg given as a single 200 mg tablet (using the immediate release formulation), orally administered. 2\) Treatment B (test) = 200 mg given as four 50-mg tablets (using the dispersible pediatric formulation), orally administered. 3\) Treatment C (test) = single 50-mg dispersible tablet, orally administered. 4) Treatment D (test) = single 10-mg dispersible tablet, orally administered	Panel 2: Treatment D Each participant received four single-dose treatments. Panel 2 fasted before dosing. Pretomanid: 1) Treatment A (reference) = 200 mg given as a single 200 mg tablet (using the immediate release formulation), orally administered. 2\) Treatment B (test) = 200 mg given as four 50-mg tablets (using the dispersible pediatric formulation), orally administered. 3\) Treatment C (test) = single 50-mg dispersible tablet, orally administered. 4) Treatment D (test) = single 10-mg dispersible tablet, orally administered
Food Effect - Ratio of AUC 0-t Fed Vs Fasted	81.74 Ratio (%) Interval 71.53 to 93.42	167.96 Ratio (%) Interval 151.4 to 186.33	188.36 Ratio (%) Interval 165.6 to 214.26	114.09 Ratio (%) Interval 99.7 to 130.55	—	—	—	—

SECONDARY outcome

Timeframe: intake (pre-dose), and at 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72, and 96 hours post dose

Food effect on bioavailability was assessed across panels based on the 90% confidence intervals (CIs) for estimates of the geometric mean ratios between AUC 0-inf of fed versus fasted across panels. An analysis of variance was used for each treatment with panel as the fixed effect

Outcome measures

Outcome measures
Measure	Treatment D Fed and Fasted n=34 Participants Each participant will receive four single-dose treatments in both fed and fasted conditions Pretomanid: 1) Treatment D(reference) = 200 mg given as a single 200 mg tablet (using the immediate release formulation), orally administered.	Treatment A Fed and Fasted n=48 Participants Each participant will receive four single-dose treatments in both fed and fasted conditions. Treatment A (reference) = 200 mg pretomanid given as a single 200 mg tablet (using the immediate release formulation), orally administered	Treatment B Fed and Fasted n=48 Participants Each participant will receive four single-dose treatments in both fed and fasted conditions Treatment B (test) = 200 mg given as four 50-mg tablets (using the dispersible pediatric formulation), orally administered.	Treatment C Fed and Fasted n=46 Participants Each participant will receive four single-dose treatments in both fed and fasted conditions Treatment C (test) = single 50-mg dispersible tablet, orally administered.	Panel 2:Treatment A Each participant received four single-dose treatments. Panel 2 fasted before dosing. Pretomanid: 1) Treatment A (reference) = 200 mg given as a single 200 mg tablet (using the immediate release formulation), orally administered. 2\) Treatment B (test) = 200 mg given as four 50-mg tablets (using the dispersible pediatric formulation), orally administered. 3\) Treatment C (test) = single 50-mg dispersible tablet, orally administered. 4) Treatment D (test) = single 10-mg dispersible tablet, orally administered	Panel 2: Treatment B Each participant received four single-dose treatments. Panel 2 fasted before dosing. Pretomanid: 1) Treatment A (reference) = 200 mg given as a single 200 mg tablet (using the immediate release formulation), orally administered. 2\) Treatment B (test) = 200 mg given as four 50-mg tablets (using the dispersible pediatric formulation), orally administered. 3\) Treatment C (test) = single 50-mg dispersible tablet, orally administered. 4) Treatment D (test) = single 10-mg dispersible tablet, orally administered	Panel 2: Treatment C Each participant received four single-dose treatments. Panel 2 fasted before dosing. Pretomanid: 1) Treatment A (reference) = 200 mg given as a single 200 mg tablet (using the immediate release formulation), orally administered. 2\) Treatment B (test) = 200 mg given as four 50-mg tablets (using the dispersible pediatric formulation), orally administered. 3\) Treatment C (test) = single 50-mg dispersible tablet, orally administered. 4) Treatment D (test) = single 10-mg dispersible tablet, orally administered	Panel 2: Treatment D Each participant received four single-dose treatments. Panel 2 fasted before dosing. Pretomanid: 1) Treatment A (reference) = 200 mg given as a single 200 mg tablet (using the immediate release formulation), orally administered. 2\) Treatment B (test) = 200 mg given as four 50-mg tablets (using the dispersible pediatric formulation), orally administered. 3\) Treatment C (test) = single 50-mg dispersible tablet, orally administered. 4) Treatment D (test) = single 10-mg dispersible tablet, orally administered
Food Effect - Ratio of AUC 0-inf Fed Vs Fasted	81.57 Ratio (%) Interval 71.07 to 93.61	166.38 Ratio (%) Interval 149.07 to 185.69	187.54 Ratio (%) Interval 163.44 to 215.2	113.58 Ratio (%) Interval 98.52 to 130.95	—	—	—	—

SECONDARY outcome

Timeframe: throughout the study, approximately 33 days

Population: All participants randomized

All listed adverse events (AEs) are treatment emergent adverse events (TEAE) which are defined as AEs that started or worsened at or after the first administration of IMP up to and including