A Phase 1/2 interventional study of Rifapentine (RPT) and Isoniazid (INH) in Tuberculosis, sponsored by National Institute of Allergy and Infectious Diseases (NIAID). Completed at 5 sites in 5 countries. Open to female participants aged 18 Years and older, including healthy volunteers. Per ClinicalTrials.gov, last updated 2021-11-04.
Sponsored by National Institute of Allergy and Infectious Diseases (NIAID) · Phase 1/2, Interventional, and Treatment
The purpose of this study was to evaluate the pharmacokinetics (PK), tolerability, and safety of once-weekly doses of rifapentine (RPT) and isoniazid (INH) in HIV-1-infected and HIV-1-uninfected pregnant and postpartum women with latent tuberculosis (TB).
TB is a major cause of illness and death in women of reproductive age. Pregnant and postpartum women with latent TB are at higher risk of developing active TB. This study evaluated the pharmacokinetics, tolerability, and safety of 12 once-weekly doses of RPT and INH in HIV-1-infected and HIV-1-uninfected pregnant and postpartum women with latent TB.
This study enrolled HIV-1-infected and HIV-1-uninfected pregnant women with latent TB and their infants into two cohorts based on gestation. Cohort 1 participants were enrolled in their second trimester (greater than or equal to 14 to less than 28 weeks), and Cohort 2 participants were enrolled in their third trimester (greater than or equal to 28 to less than or equal to 34 weeks). All participants received 12 directly observed once-weekly doses of RPT, INH, and pyridoxine (vitamin B6) at study entry and at 11 weekly follow-up visits. Study researchers would perform an interim analysis to assess the PK of RPT during the study, and a dose adjustment could have been recommended based on this analysis.
Study visits occurred at days 0-3, once a week through week 11, and once a month until 24 weeks after delivery. Visits would include physical examinations, obstetrical exams, and blood collection. Infants were followed monthly until 24 weeks after birth.
1,170 studies on the registry are indexed under Tuberculosis; 175 are open to participants now.
This study's enrollment of 50 is below the median of 150 across 820 interventional studies indexed under Tuberculosis.
Browse Tuberculosis studies →National Institute of Allergy and Infectious Diseases (NIAID) is the lead sponsor of 2,446 studies on the registry; 179 are open to participants now.
Of its 405 completed or terminated interventional studies of FDA-regulated products, 302 (75%) have results posted.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Had at least one of the following risk factors for TB:
NOTE: A household contact was defined as a person who currently lives or lived in the same dwelling unit and shares or shared the same housekeeping arrangements and who reported exposure within the past two years to an adult index case with pulmonary TB. Shared housekeeping arrangements were defined as sleeping under the same roof as the index TB case for at least seven consecutive days during the one month prior to the index case TB diagnosis.
Documented laboratory values obtained within 14 days prior to enrollment:
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.
Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.
The number of neutrophils, white blood cells that help fight infection, in a given amount of blood. Too few raises the risk of infection.
It is a count, not a percentage of the white cells. Limits are written in units that mean the same: ≥ 1.5 × 10⁹/L is ≥ 1,500 per mm³ (µL). Each lab has its own reference range.
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HIV
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hemoglobin (Hb)
The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ALT and AST (liver enzymes)
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ULN (upper limit of normal)
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Bilirubin
A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.
Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Absolute neutrophil count (ANC)
The number of neutrophils, white blood cells that help fight infection, in a given amount of blood. Too few raises the risk of infection.
It is a count, not a percentage of the white cells. Limits are written in units that mean the same: ≥ 1.5 × 10⁹/L is ≥ 1,500 per mm³ (µL). Each lab has its own reference range.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Platelets
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hypersensitivity
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Participants received 12 directly observed once-weekly doses of RPT, INH, and pyridoxine (vitamin B6) at study entry and at 11 weekly follow-up visits.
Drug: Rifapentine (RPT) · Drug: Isoniazid (INH) · Dietary Supplement: Pyridoxine (vitamin B6)
Participants received 12 directly observed once-weekly doses of RPT, INH, and pyridoxine (vitamin B6) at study entry and at 11 weekly follow-up visits.
Drug: Rifapentine (RPT) · Drug: Isoniazid (INH) · Dietary Supplement: Pyridoxine (vitamin B6)
900 mg of RPT
Also known as: Rifamycin
900 mg of INH
Also known as: isonicotinyl hydrazine,
25 mg to 100 mg of pyridoxine, based on the current local, national, or international dosing guidelines.
Also known as: Vitamin B6
Clearance Relative to Bioavailability (CL/F) for Rifapentine (RPT) for Intensive and Sparse PK
PK parameters were determined from plasma concentration-time profiles using a nonlinear mixed effects model (version 7.4; ICON PLC, Dublin, Ireland). * Developed a 1 compartment PK model with transit compartments for oral absorption * Calculated an average CL for all women in the 2nd trimester (cohort I) and all women in the 3rd trimester (cohort II)
Time frame: Data used in the population PK analysis included the intensive PK visit (pre-dose (t0) and 0.5, 1, 2. 4, 5, 8, 12, 24, 48, 72 hours post-dose) and sparse PK visit (1, 4, 24, 48 hours post-dose).
Clearance Relative to Bioavailability (CLmet/F) for Desacetyl Rifapentine (Des-RPT)
PK parameters were determined from plasma concentration-time profiles using a nonlinear mixed effects model (version 7.4; ICON PLC, Dublin, Ireland). * Developed a 1 compartment PK model with transit compartments for oral absorption and a separate compartment for metabolite formation * Estimated a single des-RPT CLmet/F for the whole population Note: that the mean stated below is actually the value that is obtained from a population analysis and represents a population estimate with the relative standard error
Time frame: Data used in the population PK analysis included the intensive PK visit (pre-dose (t0) and 0.5, 1, 2. 4, 5, 8, 12, 24, 48, 72 hours post-dose) and sparse PK visit (1, 4, 24, 48 hours post-dose).
Absorption Rate Constant (ka) for Rifapentine (RPT)
PK parameters were determined from plasma concentration-time profiles using a nonlinear mixed effects model (version 7.4; ICON PLC, Dublin, Ireland). * Developed a 1 compartment PK model with transit compartments for oral absorption * Estimated the transit compartment rate constant (ktr), which is synonymous with the absorption constant (ka), for the whole population Note that the mean stated below is actually the value that is obtained from a population analysis and represents a population estimate
Time frame: Data used in the population PK analysis included the intensive PK visit (pre-dose (t0) and 0.5, 1, 2. 4, 5, 8, 12, 24, 48, 72 hours post-dose) and sparse PK visit (1, 4, 24, 48 hours post-dose).
Volume of Distribution Relative to Bioavailability (Vc/F) for Rifapentine (RPT)
PK parameters were determined from plasma concentration-time profiles using a nonlinear mixed effects model (version 7.4; ICON PLC, Dublin, Ireland). * Developed a 1 compartment PK model with transit compartments for oral absorption * Estimated a single RPT Vc/F for for the whole population Note: that the mean stated below is actually the value that is obtained from a population analysis and represents a population estimate with the relative standard error
Time frame: Data used in the population PK analysis included the intensive PK visit (pre-dose (t0) and 0.5, 1, 2. 4, 5, 8, 12, 24, 48, 72 hours post-dose) and sparse PK visit (1, 4, 24, 48 hours post-dose).
Incidence of Related Serious Adverse Events (SAEs) in Pregnant and Postpartum Women Taking Once-weekly RPT + INH
At entry and follow-up, all lab results, sign and symptoms, and diagnoses were recorded. Also, during follow-up grade 2 events related to pregnancy complications, hepatotoxicity, hemorrhage, or peripheral neuropathy, and all grade 3 or events that resulted in discontinuation of study drug regimen, and that met criteria for EAE reporting would further be evaluated and recorded. The DAIDS Table for Grading Adult and Pediatric Adverse Events (V 2.0) and Expedited AE Manual (V 2.0) were used.
Time frame: Measured from entry through participants' last study visit at 24 weeks after delivery
Percentage of Participants With Grade 2 Adverse Events (AEs) Judged to be Related to Study Drug Regimen
At entry and follow-up, all lab results, sign and symptoms, and diagnoses were recorded. Also, during follow-up grade 2 events related to pregnancy complications, hepatotoxicity, hemorrhage, or peripheral neuropathy, and all grade 3 or events that resulted in discontinuation of study drug regimen, and that met criteria for EAE reporting would further be evaluated and recorded. The DAIDS Table for Grading Adult and Pediatric Adverse Events (V 2.0) and Expedited AE Manual (V 2.0) and were used.
Time frame: Measured from study entry through participants' last study visit at 24 weeks after delivery
Percentage of Participants With All Grade 3 and 4 AEs
At entry and follow-up, all lab results, sign and symptoms, and diagnoses were recorded. Also, during follow-up grade 2 events related to pregnancy complications, hepatotoxicity, hemorrhage, or peripheral neuropathy, and all grade 3 or events that resulted in discontinuation of study drug regimen, and that met criteria for EAE reporting would further be evaluated and recorded. The DAIDS Table for Grading Adult and Pediatric Adverse Events (V 2.0) and Expedited AE Manual (V 2.0) were used.
Time frame: Measured from study entry through participants' last study visit at 24 weeks after delivery
Percentage of Participants With All Serious AEs
At entry and follow-up, all lab results, sign and symptoms, and diagnoses were recorded. Also, during follow-up grade 2 events related to pregnancy complications, hepatotoxicity, hemorrhage, or peripheral neuropathy, and all grade 3 or events that resulted in discontinuation of study drug regimen, and that met criteria for EAE reporting would further be evaluated and recorded. The DAIDS Table for Grading Adult and Pediatric Adverse Events (V 2.0) and Expedited AE Manual (V 2.0) were used.
Time frame: Measured from study entry through participants' last study visit at 24 weeks after delivery
Percentage of Participants With All AEs Leading to Permanent Discontinuation of Study Drug Regimen (i.e., RPT, INH, and Pyridoxine)
At entry and follow-up, all lab results, sign and symptoms, and diagnoses were recorded. Also, during follow-up grade 2 events related to pregnancy complications, hepatotoxicity, hemorrhage, or peripheral neuropathy, and all grade 3 or events that resulted in discontinuation of study drug regimen, and that met criteria for EAE reporting would further be evaluated and recorded. The DAIDS Table for Grading Adult and Pediatric Adverse Events (V 2.0) and Expedited AE Manual (V 2.0) were used.
Time frame: Measured from study entry through participants' last study treatment dispensation (approximately for 12 weeks)
Percentage of Participants With Related Serious Adverse Events (AEs) in Infants Born to Women Taking Once-weekly RPT + INH
At entry and follow-up, all lab results, sign and symptoms, and diagnoses were recorded. Also, during follow-up grade 2 events related to pregnancy complications, hepatotoxicity, hemorrhage, or peripheral neuropathy, and all grade 3 or events that resulted in discontinuation of study drug regimen, and that met criteria for EAE reporting would further be evaluated and recorded. The DAIDS Table for Grading Adult and Pediatric Adverse Events (V 2.0) and Expedited AE Manual (V 2.0) were used.
Time frame: Measured from birth through infants' last study visit at 24 weeks after birth
Clearance Relative to Bioavailability (CL/F) for Rifapentine (RPT)
PK parameters from postpartum women were determined from plasma concentration-time profiles using a nonlinear mixed effects model (version 7.4; ICON PLC, Dublin, Ireland). * Developed a 1 compartment PK model with transit compartments for oral absorption * Calculated an average CL for all post-partum individuals
Time frame: Data used in the population PK analysis for postpartum women included the intensive PK visit (pre-dose (t0) and 0.5, 1, 2. 4, 5, 8, 12, 24, 48, 72 hours post-dose) and sparse PK visit (1, 4, 24, 48 hours post-dose).
Area Under the Curve From 0 to 24 Hours (AUC0-24) for RPT and Area Under the Curve From 0 to 24 Hours (AUC0-24) for Des-RPT Pregnant Women in 2nd and 3rd Trimester
PK parameters were determined from plasma concentration-time profiles using a nonlinear mixed effects model (version 7.4; ICON PLC, Dublin, Ireland). * Developed a 1 compartment PK model with transit compartments for oral absorption * Obtained AUC by model-based integration
Time frame: Data used in the population PK analysis included the intensive PK visit (pre-dose (t0) and 0.5, 1, 2. 4, 5, 8, 12, 24, 48, 72 hours post-dose) and sparse PK visit (1, 4, 24, 48 hours post-dose).
Maximum Concentration (Cmax) for RPT Maximum Concentration (Cmax) for Des-RPT Pregnant Women in 2nd and 3rd Trimester
PK parameters were determined from plasma concentration-time profiles using a nonlinear mixed effects model (version 7.4; ICON PLC, Dublin, Ireland). * Developed a 1 compartment PK model with transit compartments for oral absorption * Obtained Cmax by model-based estimation
Time frame: Data used in the population PK analysis included the intensive PK visit (pre-dose (t0) and 0.5, 1, 2. 4, 5, 8, 12, 24, 48, 72 hours post-dose) and sparse PK visit (1, 4, 24, 48 hours post-dose).
Maximum Concentration (Cmin) for RPT and Maximum Concentration (Cmin) for Des-RPT Pregnant Women in 2nd and 3rd Trimester
PK parameters were determined from plasma concentration-time profiles using a nonlinear mixed effects model (version 7.4; ICON PLC, Dublin, Ireland). * Developed a 1 compartment PK model with transit compartments for oral absorption * Obtained Cmin by model-based estimation
Time frame: Data used in the population PK analysis included the intensive PK visit (pre-dose (t0) and 0.5, 1, 2. 4, 5, 8, 12, 24, 48, 72 hours post-dose) and sparse PK visit (1, 4, 24, 48 hours post-dose).
Cord Blood Concentrations of Rifapentine (RPT) Among Infants
Cord blood concentrations were summarized using using R (version 3.5.1).
Time frame: at delivery - (within 3 days of life for infants)
Plasma Concentrations of Rifapentine (RPT) Among Infants
Plasma concentrations were summarized using using R (version 3.5.1).
Time frame: at delivery - (within 3 days of life for infants).
Cord Blood Concentrations of Desacetyl Rifapentine (Des-RPT) Among Infants
Cord blood concentrations were summarized using using R (version 3.5.1).
Time frame: at delivery (within 3 days of life for infants).
Plasma Concentrations of Desacetyl Rifapentine (Des-RPT) Among Infants
Plasma blood concentrations were summarized using using R (version 3.5.1).
Time frame: at delivery - (within 3 days of life for infants).
Number of Participants With Discontinuation of Study Drug Due to Intolerance (Tolerability of Study Drug Regimen - i.e., RPT, INH, and Pyridoxine)
At entry and follow-up, all lab results, sign and symptoms, and diagnoses will be recorded. Also, during follow-up grade 2 events related to pregnancy complications, hepatotoxicity, hemorrhage, or peripheral neuropathy, and all grade 3 or events that result in discontinuation of study drug regimen, and that meet criteria for EAE reporting will be further evaluated and recorded. The DAIDS Table for Grading Adult and Pediatric Adverse Events (V 2.0) and Expedited AE Manual (V 2.0) were used.
Time frame: Measured from study entry through participants' last study visit at 24 weeks after delivery
Number of Mothers With Active TB up to 24 Weeks Postpartum
Based on site-specified confirmatory TB test. If women and infants were diagnosed with active TB during study they would be referred to local care for TB management and treatment.
Time frame: Measured from study entry through participants' last study visit at 24 weeks after delivery
Number of Infants With Active TB up to 24 Weeks of Life
Based on site-specified confirmatory TB test. If women and infants were diagnosed with active TB during study they would be referred to local care for TB management and treatment.
Time frame: Measured from birth through participants' last study visit at 24 weeks after delivery
Clearance (CL/F) of INH
PK parameters were determined from plasma concentration-time profiles using a nonlinear mixed effects model (version 7.4; ICON PLC, Dublin, Ireland). * Developed a 1 compartment PK model with 2 mixtures to characterize subpopulations based on acetylation status * Estimated a separate INH CL/F based on acetylation status (fast, slow)
Time frame: Data used in the population PK analysis included the intensive PK visit (pre-dose (t0) and 0.5, 1, 2. 4, 5, 8, 12, 24, 48, 72 hours post-dose) and sparse PK visit (1, 4, 24, 48 hours post-dose).
Absorption (ka) of INH
PK parameters were determined from plasma concentration-time profiles using a nonlinear mixed effects model (version 7.4; ICON PLC, Dublin, Ireland). • Estimated a single absorption rate constant (ka) for the whole population
Time frame: Data used in the population PK analysis included the intensive PK visit (pre-dose (t0) and 0.5, 1, 2. 4, 5, 8, 12, 24, 48, 72 hours post-dose) and sparse PK visit (1, 4, 24, 48 hours post-dose).
Volume of Distribution of INH
PK parameters were determined from plasma concentration-time profiles using a nonlinear mixed effects model (version 7.4; ICON PLC, Dublin, Ireland). • Estimated a single INH Vc/F for the whole population
Time frame: Data used in the population PK analysis included the intensive PK visit (pre-dose (t0) and 0.5, 1, 2. 4, 5, 8, 12, 24, 48, 72 hours post-dose) and sparse PK visit (1, 4, 24, 48 hours post-dose).
The first participant was enrolled on March 13, 2017 and accrual was completed on June 12, 2018 across the following sites: Siriraj Hospital, Mahidol University NIC (CRS 5115), Kenya Medical Research Institute/Walter Reed Project (CRS 5121), Malawi (CRS 12001), the Les Centres GHESKIO INLR (CRS 30022), and Harare Family Care (CRS 31890).
| Milestone | Cohort 1 (Pregnant Women Enrolled in the Second Trimester) | Cohort 2 (Pregnant Women Enrolled in the Third Trimester) |
|---|---|---|
| Started | 25 | 25 |
| Completed | 25 | 25 |
| Not completed | 0 | 0 |
PK parameters were determined from plasma concentration-time profiles using a nonlinear mixed effects model (version 7.4; ICON PLC, Dublin, Ireland). * Developed a 1 compartment PK model with transit compartments for oral absorption * Calculated an average CL for all women in the 2nd trimester (cohort I) and all women in the 3rd trimester (cohort II)
| L/hr | Cohort 1 (Pregnant Women Enrolled in the Second Trimester) | Cohort 2 (Pregnant Women Enrolled in the Third Trimester) |
|---|---|---|
| Clearance Relative to Bioavailability (CL/F) for Rifapentine (RPT) for Intensive and Sparse PK | 1.4 (1.26 to 1.60) | 1.50 (1.25 to 1.66) |
PK parameters were determined from plasma concentration-time profiles using a nonlinear mixed effects model (version 7.4; ICON PLC, Dublin, Ireland). * Developed a 1 compartment PK model with transit compartments for oral absorption and a separate compartment for metabolite formation * Estimated a single des-RPT CLmet/F for the whole population Note: that the mean stated below is actually the value that is obtained from a population analysis and represents a population estimate with the relative standard error
| L/hr | All Cohorts |
|---|---|
| Clearance Relative to Bioavailability (CLmet/F) for Desacetyl Rifapentine (Des-RPT) | 2.82 ± 7 |
PK parameters were determined from plasma concentration-time profiles using a nonlinear mixed effects model (version 7.4; ICON PLC, Dublin, Ireland). * Developed a 1 compartment PK model with transit compartments for oral absorption * Estimated the transit compartment rate constant (ktr), which is synonymous with the absorption constant (ka), for the whole population Note that the mean stated below is actually the value that is obtained from a population analysis and represents a population estimate
| hr-1 | All Cohorts |
|---|---|
| Absorption Rate Constant (ka) for Rifapentine (RPT) | 1.43 ± NA |
PK parameters were determined from plasma concentration-time profiles using a nonlinear mixed effects model (version 7.4; ICON PLC, Dublin, Ireland). * Developed a 1 compartment PK model with transit compartments for oral absorption * Estimated a single RPT Vc/F for for the whole population Note: that the mean stated below is actually the value that is obtained from a population analysis and represents a population estimate with the relative standard error
| L | All Cohorts |
|---|---|
| Volume of Distribution Relative to Bioavailability (Vc/F) for Rifapentine (RPT) | 30.1 ± 5 |
At entry and follow-up, all lab results, sign and symptoms, and diagnoses were recorded. Also, during follow-up grade 2 events related to pregnancy complications, hepatotoxicity, hemorrhage, or peripheral neuropathy, and all grade 3 or events that resulted in discontinuation of study drug regimen, and that met criteria for EAE reporting would further be evaluated and recorded. The DAIDS Table for Grading Adult and Pediatric Adverse Events (V 2.0) and Expedited AE Manual (V 2.0) were used.
| Participants | Cohort 1 (Pregnant Women Enrolled in the Second Trimester) | Cohort 2 (Pregnant Women Enrolled in the Third Trimester) |
|---|---|---|
| Incidence of Related Serious Adverse Events (SAEs) in Pregnant and Postpartum Women Taking Once-weekly RPT + INH | 0 | 0 |
At entry and follow-up, all lab results, sign and symptoms, and diagnoses were recorded. Also, during follow-up grade 2 events related to pregnancy complications, hepatotoxicity, hemorrhage, or peripheral neuropathy, and all grade 3 or events that resulted in discontinuation of study drug regimen, and that met criteria for EAE reporting would further be evaluated and recorded. The DAIDS Table for Grading Adult and Pediatric Adverse Events (V 2.0) and Expedited AE Manual (V 2.0) and were used.
| percent of participants | Cohort 1 (Pregnant Women Enrolled in the Second Trimester) | Cohort 2 (Pregnant Women Enrolled in the Third Trimester) |
|---|---|---|
| Percentage of Participants With Grade 2 Adverse Events (AEs) Judged to be Related to Study Drug Regimen | 4 (0.1 to 20) | 0 (0 to 14) |
At entry and follow-up, all lab results, sign and symptoms, and diagnoses were recorded. Also, during follow-up grade 2 events related to pregnancy complications, hepatotoxicity, hemorrhage, or peripheral neuropathy, and all grade 3 or events that resulted in discontinuation of study drug regimen, and that met criteria for EAE reporting would further be evaluated and recorded. The DAIDS Table for Grading Adult and Pediatric Adverse Events (V 2.0) and Expedited AE Manual (V 2.0) were used.
| percent of participants | Cohort 1 (Pregnant Women Enrolled in the Second Trimester) | Cohort 2 (Pregnant Women Enrolled in the Third Trimester) |
|---|---|---|
| Percentage of Participants With All Grade 3 and 4 AEs | 20 (7 to 41) | 16 (5 to 36) |
At entry and follow-up, all lab results, sign and symptoms, and diagnoses were recorded. Also, during follow-up grade 2 events related to pregnancy complications, hepatotoxicity, hemorrhage, or peripheral neuropathy, and all grade 3 or events that resulted in discontinuation of study drug regimen, and that met criteria for EAE reporting would further be evaluated and recorded. The DAIDS Table for Grading Adult and Pediatric Adverse Events (V 2.0) and Expedited AE Manual (V 2.0) were used.
| percent of participants | Cohort 1 (Pregnant Women Enrolled in the Second Trimester) | Cohort 2 (Pregnant Women Enrolled in the Third Trimester) |
|---|---|---|
| Percentage of Participants With All Serious AEs | 8 (1 to 26) | 12 (3 to 31) |
At entry and follow-up, all lab results, sign and symptoms, and diagnoses were recorded. Also, during follow-up grade 2 events related to pregnancy complications, hepatotoxicity, hemorrhage, or peripheral neuropathy, and all grade 3 or events that resulted in discontinuation of study drug regimen, and that met criteria for EAE reporting would further be evaluated and recorded. The DAIDS Table for Grading Adult and Pediatric Adverse Events (V 2.0) and Expedited AE Manual (V 2.0) were used.
| percent of participants | Cohort 1 (Pregnant Women Enrolled in the Second Trimester) | Cohort 2 (Pregnant Women Enrolled in the Third Trimester) |
|---|---|---|
| Percentage of Participants With All AEs Leading to Permanent Discontinuation of Study Drug Regimen (i.e., RPT, INH, and Pyridoxine) | 0 (0 to 14) | 0 (0 to 14) |
At entry and follow-up, all lab results, sign and symptoms, and diagnoses were recorded. Also, during follow-up grade 2 events related to pregnancy complications, hepatotoxicity, hemorrhage, or peripheral neuropathy, and all grade 3 or events that resulted in discontinuation of study drug regimen, and that met criteria for EAE reporting would further be evaluated and recorded. The DAIDS Table for Grading Adult and Pediatric Adverse Events (V 2.0) and Expedited AE Manual (V 2.0) were used.
| percent of participants | Cohort 1 (Infants Born to Women Enrolled in Second Trimester) | Cohort 2 (Infants Born to Women Enrolled in Third Trimester) |
|---|---|---|
| Percentage of Participants With Related Serious Adverse Events (AEs) in Infants Born to Women Taking Once-weekly RPT + INH | 0 (0 to 14) | 0 (0 to 14) |
PK parameters from postpartum women were determined from plasma concentration-time profiles using a nonlinear mixed effects model (version 7.4; ICON PLC, Dublin, Ireland). * Developed a 1 compartment PK model with transit compartments for oral absorption * Calculated an average CL for all post-partum individuals
| L/hr | All Cohorts |
|---|---|
| Clearance Relative to Bioavailability (CL/F) for Rifapentine (RPT) | 1.64 (1.6 to 1.68) |
PK parameters were determined from plasma concentration-time profiles using a nonlinear mixed effects model (version 7.4; ICON PLC, Dublin, Ireland). * Developed a 1 compartment PK model with transit compartments for oral absorption * Obtained AUC by model-based integration
| hour*mg/L | Cohort 1 (Pregnant Women Enrolled in the Second Trimester) | Cohort 2 (Pregnant Women Enrolled in the Third Trimester) |
|---|---|---|
| AUC (0-24) for RPT | 424.7 (341.7 to 514.1) | 406.8 (334.8 to 471.7) |
| AUC (0-24) for des-RPT | 158.7 (118.9 to 184.3) | 153.7 (123.1 to 186.4) |
PK parameters were determined from plasma concentration-time profiles using a nonlinear mixed effects model (version 7.4; ICON PLC, Dublin, Ireland). * Developed a 1 compartment PK model with transit compartments for oral absorption * Obtained Cmax by model-based estimation
| mg/L | Cohort 1 (Pregnant Women Enrolled in the Second Trimester) | Cohort 2 (Pregnant Women Enrolled in the Third Trimester) |
|---|---|---|
| Cmax for RPT | 30.2 (25.1 to 36.1) | 28.6 (24.7 to 32.1) |
| Cmax for des-RPT | 8.76 (5.91 to 10.8) | 8.50 (6.82 to 10.0) |
PK parameters were determined from plasma concentration-time profiles using a nonlinear mixed effects model (version 7.4; ICON PLC, Dublin, Ireland). * Developed a 1 compartment PK model with transit compartments for oral absorption * Obtained Cmin by model-based estimation
| mg/L | Cohort 1 (Pregnant Women Enrolled in the Second Trimester) | Cohort 2 (Pregnant Women Enrolled in the Third Trimester) |
|---|---|---|
| Cmin for RPT | 1.45 (0.84 to 1.98) | 1.58 (0.66 to 2.29) |
| Cmin for des-RPT | 1.06 (0.63 to 1.25) | 1.20 (0.79 to 1.74) |
Cord blood concentrations were summarized using using R (version 3.5.1).
| mcg/mL | All Cohorts |
|---|---|
| Cord Blood Concentrations of Rifapentine (RPT) Among Infants | 2.97 (1.94 to 4.26) |
Plasma concentrations were summarized using using R (version 3.5.1).
| mcg/mL | All Cohorts |
|---|---|
| Plasma Concentrations of Rifapentine (RPT) Among Infants | 2.47 (1.49 to 3.30) |
Cord blood concentrations were summarized using using R (version 3.5.1).
| mcg/mL | All Cohorts |
|---|---|
| Cord Blood Concentrations of Desacetyl Rifapentine (Des-RPT) Among Infants | 3.24 (1.03 to 5.17) |
Plasma blood concentrations were summarized using using R (version 3.5.1).
| mcg/mL | All Cohorts |
|---|---|
| Plasma Concentrations of Desacetyl Rifapentine (Des-RPT) Among Infants | 5.31 (3.73 to 7.37) |
At entry and follow-up, all lab results, sign and symptoms, and diagnoses will be recorded. Also, during follow-up grade 2 events related to pregnancy complications, hepatotoxicity, hemorrhage, or peripheral neuropathy, and all grade 3 or events that result in discontinuation of study drug regimen, and that meet criteria for EAE reporting will be further evaluated and recorded. The DAIDS Table for Grading Adult and Pediatric Adverse Events (V 2.0) and Expedited AE Manual (V 2.0) were used.
| Participants | Cohort 1 (Pregnant Women Enrolled in the Second Trimester) | Cohort 2 (Pregnant Women Enrolled in the Third Trimester) |
|---|---|---|
| Number of Participants With Discontinuation of Study Drug Due to Intolerance (Tolerability of Study Drug Regimen - i.e., RPT, INH, and Pyridoxine) | 0 | 0 |
Based on site-specified confirmatory TB test. If women and infants were diagnosed with active TB during study they would be referred to local care for TB management and treatment.
| Participants | Cohort 1 (Pregnant Women Enrolled in the Second Trimester) | Cohort 2 (Pregnant Women Enrolled in the Third Trimester) |
|---|---|---|
| Number of Mothers With Active TB up to 24 Weeks Postpartum | 0 | 0 |
Based on site-specified confirmatory TB test. If women and infants were diagnosed with active TB during study they would be referred to local care for TB management and treatment.
| Participants | Cohort 1(Infants Born to Women Enrolled in Second Trimester) | Cohort 2 (Infants Born to Women Enrolled in Third Trimester) |
|---|---|---|
| Number of Infants With Active TB up to 24 Weeks of Life | 0 | 0 |
PK parameters were determined from plasma concentration-time profiles using a nonlinear mixed effects model (version 7.4; ICON PLC, Dublin, Ireland). * Developed a 1 compartment PK model with 2 mixtures to characterize subpopulations based on acetylation status * Estimated a separate INH CL/F based on acetylation status (fast, slow)
| L/hr | All Cohorts |
|---|---|
| CL/F (slow acetylators) | 8.98 ± 47 |
| CL/F (fast acetylators) | 32.7 ± 10 |
PK parameters were determined from plasma concentration-time profiles using a nonlinear mixed effects model (version 7.4; ICON PLC, Dublin, Ireland). • Estimated a single absorption rate constant (ka) for the whole population
| hr-1 | All Cohorts |
|---|---|
| Absorption (ka) of INH | 1.74 ± 49 |
PK parameters were determined from plasma concentration-time profiles using a nonlinear mixed effects model (version 7.4; ICON PLC, Dublin, Ireland). • Estimated a single INH Vc/F for the whole population
| L | All Cohorts |
|---|---|
| Volume of Distribution of INH | 107 ± 12 |
Collected over Measured from study entry through participants last study visit at 24 weeks after delivery. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Cohort 1 (Pregnant Women Enrolled in Their Second Trimester) | 1/25 (4%) | 2/25 (8%) | 24/25 (96%) |
| Cohort 2 (Pregnant Women Enrolled in Their Third Trimester) | 0/25 (0%) | 3/25 (12%) | 25/25 (100%) |
| Event | Cohort 1 (Pregnant Women Enrolled in Their Second Trimester) | Cohort 2 (Pregnant Women Enrolled in Their Third Trimester) |
|---|---|---|
| Gestational hypertensionPregnancy, puerperium and perinatal conditions | 0/25 | 2/25 |
| Premature separation of placentaPregnancy, puerperium and perinatal conditions | 2/25 | 0/25 |
| Postpartum haemorrhagePregnancy, puerperium and perinatal conditions | 0/25 | 1/25 |
| Event | Cohort 1 (Pregnant Women Enrolled in Their Second Trimester) | Cohort 2 (Pregnant Women Enrolled in Their Third Trimester) |
|---|---|---|
| Blood albumin decreasedInvestigations | 20/25 | 21/25 |
| Haemoglobin decreasedInvestigations | 15/25 | 10/25 |
| Pelvic painReproductive system and breast disorders | 8/25 | 4/25 |
| Aspartate aminotransferase increasedInvestigations | 6/25 | 7/25 |
| HeadacheNervous system disorders | 6/25 | 5/25 |
| Abdominal painGastrointestinal disorders | 5/25 | 3/25 |
| Abdominal pain upperGastrointestinal disorders | 5/25 | 2/25 |
| MalaiseGeneral disorders | 5/25 | 0/25 |
| Alanine aminotransferase increasedInvestigations | 4/25 | 5/25 |
| Blood pressure increasedInvestigations | 5/25 | 3/25 |
| Age, Categorical(Participants) | Cohort 1 (Pregnant Women Enrolled in the Second Trimester) | Cohort 2 (Pregnant Women Enrolled in the Third Trimester) | Total |
|---|---|---|---|
| <=18 years | 1 | 3 | 4 |
| Between 18 and 65 years | 24 | 22 | 46 |
| >=65 years | 0 | 0 | 0 |
| Age, Continuous(years) | Cohort 1 (Pregnant Women Enrolled in the Second Trimester) | Cohort 2 (Pregnant Women Enrolled in the Third Trimester) | Total |
|---|---|---|---|
| Median | 26 (22 to 33) | 27 (20 to 31) | 27 (20 to 32) |
| Sex: Female, Male(Participants) | Cohort 1 (Pregnant Women Enrolled in the Second Trimester) | Cohort 2 (Pregnant Women Enrolled in the Third Trimester) | Total |
|---|---|---|---|
| Female | 25 | 25 | 50 |
| Male | 0 | 0 | 0 |
| Race/Ethnicity, Customized(Participants) | Cohort 1 (Pregnant Women Enrolled in the Second Trimester) | Cohort 2 (Pregnant Women Enrolled in the Third Trimester) | Total |
|---|---|---|---|
| Black Non-Hispanic | 24 | 23 | 47 |
| Asian, Pacific Islander | 1 | 2 | 3 |
| Region of Enrollment(participants) | Cohort 1 (Pregnant Women Enrolled in the Second Trimester) | Cohort 2 (Pregnant Women Enrolled in the Third Trimester) | Total |
|---|---|---|---|
| Haiti | 11 | 5 | 16 |
| Malawi | 2 | 1 | 3 |
| Zimbabwe | 9 | 12 | 21 |
| Kenya | 2 | 5 | 7 |
| Thailand | 1 | 2 | 3 |
| HIV-1 status(Participants) | Cohort 1 (Pregnant Women Enrolled in the Second Trimester) | Cohort 2 (Pregnant Women Enrolled in the Third Trimester) | Total |
|---|---|---|---|
| HIV-1 uninfected | 15 | 15 | 30 |
| HIV-1 infected | 10 | 10 | 20 |
| Absolute CD4 count(cells/mm^3) | Cohort 1 (Pregnant Women Enrolled in the Second Trimester) | Cohort 2 (Pregnant Women Enrolled in the Third Trimester) | Total |
|---|---|---|---|
| Median | 586 (415 to 846) | 489 (368 to 952) | 510 (390 to 877) |
| World Health Organization (WHO) clinical stage(Participants) | Cohort 1 (Pregnant Women Enrolled in the Second Trimester) | Cohort 2 (Pregnant Women Enrolled in the Third Trimester) | Total |
|---|---|---|---|
| Clinical Stage 1 | 10 | 10 | 20 |
| Clinical Stage 2 | 0 | 0 | 0 |
| Clinical Stage 3 | 0 | 0 | 0 |
| Clinical Stage 4 | 0 | 0 | 0 |
6 further baseline measures are reported on the registry.
PDFs hosted by the registry, ClinicalTrials.gov.
Ran from Mar 2017 to primary completion in Apr 2019, 24 months.
Results were first posted in May 2020, 1 year after primary completion.
Of 18 phase 1/2 interventional studies under Tuberculosis, half reached primary completion within 39 months of starting (the median), counting those still running; a quarter within 25 and three quarters within 53. This study's 24 months is below that.
How these figures are worked out, and which studies are left out of them.
This study is completed, as verified in May 2020. You cannot join it, but the record below documents what was studied.
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Studies of the drugs tested here: Rifapentine · Isoniazid
National Institute of Allergy and Infectious Diseases (NIAID) →