Trial Outcomes & Findings for Point-of-care Pharmacogenomic Testing to Optimize Isoniazid Dosing for Tuberculosis Prevention (NCT NCT05413551)

Last Updated: 2026-06-15

Results Overview

Apparent clearance (CL) of isoniazid estimated from a population pharmacokinetic model using plasma concentration data collected at 1, 2, 8, and 24 hours post-dose on Days 7 and 14. Clearance values represent model-derived population parameter estimates. Data across the day 7 and day 14 time points are combined to provide an estimated value as a model parameter, representing the typical value per group.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

78 participants

Primary outcome timeframe

Days 7 and 14 (1, 2, 8, and 24 hours post-dose)

Results posted on

2026-06-15

Participant Flow

Participants were recruited in Brazil between March 2023 and June 2025 from clinical, community, and correctional facilities in Campo Grande. Eligible participants included individuals indicated for tuberculosis preventive therapy, including healthcare workers, household contacts, incarcerated individuals, and people living with HIV.

Participant milestones

Participant milestones
Measure	Rapid Acetylator Participants will receive 1 standard dose (Day 0), followed by 1 higher dose (Day 7), follow by 2 standard doses (Days 14 and 21).	Intermediate Acetylator Participants will receive 4 standard doses (Days 0, 7, 14 and 21).	Slow Acetylator Participants will receive 1 standard dose (Day 0), followed by 1 lower dose (Day 7), followed by 2 standard doses (Days 14 and 21).
Overall Study STARTED	10	34	34
Overall Study COMPLETED	9	27	26
Overall Study NOT COMPLETED	1	7	8

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Point-of-care Pharmacogenomic Testing to Optimize Isoniazid Dosing for Tuberculosis Prevention

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Rapid Acetylator n=10 Participants Participants will receive 1 standard dose (Day 0), followed by 1 higher dose (Day 7), follow by 2 standard doses (Days 14 and 21).	Intermediate Acetylator n=34 Participants Participants will receive 4 standard doses (Days 0, 7, 14 and 21).	Slow Acetylator n=34 Participants Participants will receive 1 standard dose (Day 0), followed by 1 lower dose (Day 7), followed by 2 standard doses (Days 14 and 21).	Total n=78 Participants Total of all reporting groups
Age, Continuous	40.3 Years n=20 Participants	45.3 Years n=20 Participants	38.3 Years n=40 Participants	41.6 Years n=5 Participants
Sex/Gender, Customized Sex · Female	2 Participants n=20 Participants	11 Participants n=20 Participants	12 Participants n=40 Participants	25 Participants n=5 Participants
Sex/Gender, Customized Sex · Male	8 Participants n=20 Participants	23 Participants n=20 Participants	22 Participants n=40 Participants	53 Participants n=5 Participants
Race/Ethnicity, Customized Race · White	3 Participants n=20 Participants	11 Participants n=20 Participants	17 Participants n=40 Participants	31 Participants n=5 Participants
Race/Ethnicity, Customized Race · Black	2 Participants n=20 Participants	6 Participants n=20 Participants	5 Participants n=40 Participants	13 Participants n=5 Participants
Race/Ethnicity, Customized Race · Mixed	3 Participants n=20 Participants	17 Participants n=20 Participants	9 Participants n=40 Participants	29 Participants n=5 Participants
Race/Ethnicity, Customized Race · Yellow	2 Participants n=20 Participants	0 Participants n=20 Participants	3 Participants n=40 Participants	5 Participants n=5 Participants
Region of Enrollment Brazil	10 Participants n=20 Participants	34 Participants n=20 Participants	34 Participants n=40 Participants	78 Participants n=5 Participants
Incarceration status	7 Participants n=20 Participants	12 Participants n=20 Participants	14 Participants n=40 Participants	33 Participants n=5 Participants
Smoking	4 Participants n=20 Participants	9 Participants n=20 Participants	5 Participants n=40 Participants	18 Participants n=5 Participants
Alcohol use	2 Participants n=20 Participants	10 Participants n=20 Participants	8 Participants n=40 Participants	20 Participants n=5 Participants
Drug-use	1 Participants n=20 Participants	1 Participants n=20 Participants	2 Participants n=40 Participants	4 Participants n=5 Participants

PRIMARY outcome

Timeframe: Days 7 and 14 (1, 2, 8, and 24 hours post-dose)

Area under the plasma concentration-time curve over 24 hours (AUC₀-₂₄) for isoniazid, estimated using a population pharmacokinetic model based on plasma concentrations collected at 1, 2, 8, and 24 hours post-dose on Days 7 and 14.

Outcome measures

Outcome measures
Measure	Rapid Acetylator n=10 Participants Participants will receive 1 standard dose (Day 0), followed by 1 higher dose (Day 7), follow by 2 standard doses (Days 14 and 21).	Intermediate Acetylator n=34 Participants Participants will receive 4 standard doses (Days 0, 7, 14 and 21).	Slow Acetylator n=34 Participants Participants will receive 1 standard dose (Day 0), followed by 1 lower dose (Day 7), followed by 2 standard doses (Days 14 and 21).
Isoniazid Plasma Area-under-the-curve 900 mg Flat Dosing (day 14 post-dose)	24.4 mg·h/L Interval 19.7 to 26.1	31.0 mg·h/L Interval 26.9 to 34.9	57.6 mg·h/L Interval 50.4 to 62.3
Isoniazid Plasma Area-under-the-curve Genotype-Based Dosing (day 7 post-dose)	40.7 mg·h/L Interval 32.9 to 43.6	30.6 mg·h/L Interval 27.1 to 34.9	18.3 mg·h/L Interval 16.3 to 20.3

PRIMARY outcome

Timeframe: Days 7 and 14 (1, 2, 8, and 24 hours post-dose)

Outcome measures

Outcome measures
Measure	Rapid Acetylator n=10 Participants Participants will receive 1 standard dose (Day 0), followed by 1 higher dose (Day 7), follow by 2 standard doses (Days 14 and 21).	Intermediate Acetylator n=34 Participants Participants will receive 4 standard doses (Days 0, 7, 14 and 21).	Slow Acetylator n=34 Participants Participants will receive 1 standard dose (Day 0), followed by 1 lower dose (Day 7), followed by 2 standard doses (Days 14 and 21).
Isoniazid Clearance	38.5 L/h Standard Error 9.78	30.3 L/h Standard Error 2.02	17.6 L/h Standard Error 2.09

SECONDARY outcome

Timeframe: Days 7 and 14 (1, 2, 8, and 24 hours post-dose)

Maximum observed plasma concentration (Cmax) of isoniazid following dosing, derived from serial plasma samples collected at 1, 2, 8, and 24 hours post-dose

Outcome measures

Outcome measures
Measure	Rapid Acetylator n=10 Participants Participants will receive 1 standard dose (Day 0), followed by 1 higher dose (Day 7), follow by 2 standard doses (Days 14 and 21).	Intermediate Acetylator n=34 Participants Participants will receive 4 standard doses (Days 0, 7, 14 and 21).	Slow Acetylator n=34 Participants Participants will receive 1 standard dose (Day 0), followed by 1 lower dose (Day 7), followed by 2 standard doses (Days 14 and 21).
Maximum Isoniazid Concentration (Cmax) Genotype-Based Dosing (day 7 post-dose)	12.8 µg/mL Interval 9.84 to 14.0	7.98 µg/mL Interval 6.83 to 9.38	3.13 µg/mL Interval 2.72 to 3.56
Maximum Isoniazid Concentration (Cmax) 900 mg Flat Dosing (day 14 post-dose)	7.70 µg/mL Interval 5.9 to 8.4	7.98 µg/mL Interval 6.83 to 9.38	9.38 µg/mL Interval 8.08 to 10.7

SECONDARY outcome

Timeframe: Days 7 and 14 (24 hours post-dose)

Isoniazid plasma concentration measured at 24 hours post-dose.

Outcome measures

Outcome measures
Measure	Rapid Acetylator n=10 Participants Participants will receive 1 standard dose (Day 0), followed by 1 higher dose (Day 7), follow by 2 standard doses (Days 14 and 21).	Intermediate Acetylator n=34 Participants Participants will receive 4 standard doses (Days 0, 7, 14 and 21).	Slow Acetylator n=34 Participants Participants will receive 1 standard dose (Day 0), followed by 1 lower dose (Day 7), followed by 2 standard doses (Days 14 and 21).
Isoniazid Concentration at 24 Hours 900 mg Flat Dosing (day 14 post-dose)	0.0116 µg/mL Interval 0.0106 to 0.012	0.0226 µg/mL Interval 0.0215 to 0.0237	0.137 µg/mL Interval 0.133 to 0.141
Isoniazid Concentration at 24 Hours Genotype-Based Dosing (day 7 post-dose)	0.0194 µg/mL Interval 0.0176 to 0.02	0.0226 µg/mL Interval 0.0215 to 0.0237	0.0457 µg/mL Interval 0.0442 to 0.0471

Adverse Events

Rapid Acetylator

Serious events: 0 serious events

Other events: 7 other events

Deaths: 0 deaths

Intermediate Acetylator

Serious events: 2 serious events

Other events: 22 other events

Deaths: 0 deaths

Slow Acetylator

Serious events: 0 serious events

Other events: 24 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Rapid Acetylator n=10 participants at risk Participants will receive 1 standard dose (Day 0), followed by 1 higher dose (Day 7), follow by 2 standard doses (Days 14 and 21).	Intermediate Acetylator n=34 participants at risk Participants will receive 4 standard doses (Days 0, 7, 14 and 21).	Slow Acetylator n=34 participants at risk Participants will receive 1 standard dose (Day 0), followed by 1 lower dose (Day 7), followed by 2 standard doses (Days 14 and 21).
Nervous system disorders Dizziness with presyncope	0.00% 0/10 • 12 weeks All adverse events were reported regardless of frequency	5.9% 2/34 • 12 weeks All adverse events were reported regardless of frequency	0.00% 0/34 • 12 weeks All adverse events were reported regardless of frequency
Cardiac disorders Palpitation	0.00% 0/10 • 12 weeks All adverse events were reported regardless of frequency	2.9% 1/34 • 12 weeks All adverse events were reported regardless of frequency	0.00% 0/34 • 12 weeks All adverse events were reported regardless of frequency

Other adverse events

Other adverse events
Measure	Rapid Acetylator n=10 participants at risk Participants will receive 1 standard dose (Day 0), followed by 1 higher dose (Day 7), follow by 2 standard doses (Days 14 and 21).	Intermediate Acetylator n=34 participants at risk Participants will receive 4 standard doses (Days 0, 7, 14 and 21).	Slow Acetylator n=34 participants at risk Participants will receive 1 standard dose (Day 0), followed by 1 lower dose (Day 7), followed by 2 standard doses (Days 14 and 21).
Musculoskeletal and connective tissue disorders Myalgia	10.0% 1/10 • 12 weeks All adverse events were reported regardless of frequency	23.5% 8/34 • 12 weeks All adverse events were reported regardless of frequency	14.7% 5/34 • 12 weeks All adverse events were reported regardless of frequency
Respiratory, thoracic and mediastinal disorders Cough	20.0% 2/10 • 12 weeks All adverse events were reported regardless of frequency	8.8% 3/34 • 12 weeks All adverse events were reported regardless of frequency	14.7% 5/34 • 12 weeks All adverse events were reported regardless of frequency
General disorders Fever	0.00% 0/10 • 12 weeks All adverse events were reported regardless of frequency	5.9% 2/34 • 12 weeks All adverse events were reported regardless of frequency	2.9% 1/34 • 12 weeks All adverse events were reported regardless of frequency
Cardiac disorders Palpitations	30.0% 3/10 • 12 weeks All adverse events were reported regardless of frequency	5.9% 2/34 • 12 weeks All adverse events were reported regardless of frequency	2.9% 1/34 • 12 weeks All adverse events were reported regardless of frequency
Skin and subcutaneous tissue disorders Oral ulcer	40.0% 4/10 • 12 weeks All adverse events were reported regardless of frequency	5.9% 2/34 • 12 weeks All adverse events were reported regardless of frequency	5.9% 2/34 • 12 weeks All adverse events were reported regardless of frequency
Nervous system disorders Headache	30.0% 3/10 • 12 weeks All adverse events were reported regardless of frequency	41.2% 14/34 • 12 weeks All adverse events were reported regardless of frequency	23.5% 8/34 • 12 weeks All adverse events were reported regardless of frequency
Nervous system disorders fatigue and somnolence	10.0% 1/10 • 12 weeks All adverse events were reported regardless of frequency	17.6% 6/34 • 12 weeks All adverse events were reported regardless of frequency	14.7% 5/34 • 12 weeks All adverse events were reported regardless of frequency
Renal and urinary disorders Renal colic	0.00% 0/10 • 12 weeks All adverse events were reported regardless of frequency	2.9% 1/34 • 12 weeks All adverse events were reported regardless of frequency	5.9% 2/34 • 12 weeks All adverse events were reported regardless of frequency
Gastrointestinal disorders Epigastric pain	40.0% 4/10 • 12 weeks All adverse events were reported regardless of frequency	29.4% 10/34 • 12 weeks All adverse events were reported regardless of frequency	35.3% 12/34 • 12 weeks All adverse events were reported regardless of frequency
Gastrointestinal disorders Nausea	0.00% 0/10 • 12 weeks All adverse events were reported regardless of frequency	5.9% 2/34 • 12 weeks All adverse events were reported regardless of frequency	2.9% 1/34 • 12 weeks All adverse events were reported regardless of frequency
Psychiatric disorders Anxiety	10.0% 1/10 • 12 weeks All adverse events were reported regardless of frequency	2.9% 1/34 • 12 weeks All adverse events were reported regardless of frequency	0.00% 0/34 • 12 weeks All adverse events were reported regardless of frequency

Additional Information

Jason Andrews, Professor

Stanford University

Phone: +16504972679

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place