| Primary | 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)
| All participants with intensive and sparse PK results at all doses in all stages of pregnancy were used for analysis. | Posted | | Mean | Inter-Quartile Range | L/hr | | 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). | | | | ID | Title | Description |
|---|
| OG000 | Cohort 1 (Pregnant Women Enrolled in the Second Trimester) | 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. | | OG001 | Cohort 2 (Pregnant Women Enrolled in the Third Trimester) | 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. |
| | | Title | Denominators | Categories |
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| | | Title | Measurements |
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| - OG0001.4(1.26 to 1.60)
- OG0011.50(1.25 to 1.66)
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|
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| Primary | 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
| All participants with intensive and sparse PK results at all doses in all stages of pregnancy were used for analysis. | Posted | | Mean | Standard Error | L/hr | | 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). | | | | ID | Title | Description |
|---|
| OG000 | All Cohorts | Combined for all women in Second and Third Trimester of pregnancy |
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| Primary | 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
| All participants with intensive and sparse PK results at all doses in all stages of pregnancy were used for analysis. | Posted | | Mean | Standard Error | hr-1 | | 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). | | | | ID | Title | Description |
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| OG000 | All Cohorts | Combined for all women in Second and Third Trimester of pregnancy |
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| Primary | 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
| All participants with intensive and sparse PK results at all doses in all stages of pregnancy were used for analysis. | Posted | | Mean | Standard Error | L | | 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). | | | | ID | Title | Description |
|---|
| OG000 | All Cohorts | Combined for all women in Second and Third Trimester of pregnancy |
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| Primary | 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. | All participants enrolled in the study | Posted | | Count of Participants | | Participants | | Measured from entry through participants' last study visit at 24 weeks after delivery | | | | ID | Title | Description |
|---|
| OG000 | Cohort 1 (Pregnant Women Enrolled in the Second Trimester) | 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. | | OG001 | Cohort 2 (Pregnant Women Enrolled in the Third Trimester) | 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. |
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| Primary | 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. | All participant enrolled on the study | Posted | | Number | 95% Confidence Interval | percent of participants | | Measured from study entry through participants' last study visit at 24 weeks after delivery | | | | ID | Title | Description |
|---|
| OG000 | Cohort 1 (Pregnant Women Enrolled in the Second Trimester) | 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. | | OG001 | Cohort 2 (Pregnant Women Enrolled in the Third Trimester) | 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. |
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| Primary | 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. | All participants enrolled on the study | Posted | | Number | 95% Confidence Interval | percent of participants | | Measured from study entry through participants' last study visit at 24 weeks after delivery | | | | ID | Title | Description |
|---|
| OG000 | Cohort 1 (Pregnant Women Enrolled in the Second Trimester) | 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. | | OG001 | Cohort 2 (Pregnant Women Enrolled in the Third Trimester) | 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. |
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| Primary | 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. | All participants enrolled on the study | Posted | | Number | 95% Confidence Interval | percent of participants | | Measured from study entry through participants' last study visit at 24 weeks after delivery | | | | ID | Title | Description |
|---|
| OG000 | Cohort 1 (Pregnant Women Enrolled in the Second Trimester) | 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. | | OG001 | Cohort 2 (Pregnant Women Enrolled in the Third Trimester) | 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. |
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| Primary | 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. | All participants enrolled on the study | Posted | | Number | 95% Confidence Interval | percent of participants | | Measured from study entry through participants' last study treatment dispensation (approximately for 12 weeks) | | | | ID | Title | Description |
|---|
| OG000 | Cohort 1 (Pregnant Women Enrolled in the Second Trimester) | 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. | | OG001 | Cohort 2 (Pregnant Women Enrolled in the Third Trimester) | 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. |
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| Primary | 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. | For the 49 live born infants to the women enrolled on the study | Posted | | Number | 95% Confidence Interval | percent of participants | | Measured from birth through infants' last study visit at 24 weeks after birth | | | | ID | Title | Description |
|---|
| OG000 | Cohort 1 (Infants Born to Women Enrolled in Second Trimester) | Infants born to women who received 12 directly observed once-weekly doses of RPT, INH, and pyridoxine (vitamin B6) at study entry and at 11 weekly follow-up visits. | | OG001 | Cohort 2 (Infants Born to Women Enrolled in Third Trimester) | Infants born to women who received 12 directly observed once-weekly doses of RPT, INH, and pyridoxine (vitamin B6) at study entry and at 11 weekly follow-up visits. |
| |
| Secondary | 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
| All participants with intensive and sparse PK results at all doses postpartum were used for analysis. | Posted | | Mean | Inter-Quartile Range | L/hr | | 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). | | | | ID | Title | Description |
|---|
| OG000 | All Cohorts | |
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| Secondary | 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
| All participants with intensive and sparse PK results for RPT at all doses in all stages of pregnancy were used for analysis | Posted | | Mean | Inter-Quartile Range | hour*mg/L | | 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). | | | | ID | Title | Description |
|---|
| OG000 | Cohort 1 (Pregnant Women Enrolled in the Second Trimester) | 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. | | OG001 | Cohort 2 (Pregnant Women Enrolled in the Third Trimester) | 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. |
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| Secondary | 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
| All participants with intensive and sparse PK results for RPT at all doses in all stages of pregnancy were used for analysis. | Posted | | Mean | Inter-Quartile Range | mg/L | | 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). | | | | ID | Title | Description |
|---|
| OG000 | Cohort 1 (Pregnant Women Enrolled in the Second Trimester) | 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. | | OG001 | Cohort 2 (Pregnant Women Enrolled in the Third Trimester) | 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. |
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| Secondary | 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
| All participants with intensive and sparse PK results for RPT at all doses in all stages of pregnancy were used for analysis. | Posted | | Mean | Inter-Quartile Range | mg/L | | 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). | | | | ID | Title | Description |
|---|
| OG000 | Cohort 1 (Pregnant Women Enrolled in the Second Trimester) | 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. | | OG001 | Cohort 2 (Pregnant Women Enrolled in the Third Trimester) | 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. |
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| Secondary | Cord Blood Concentrations of Rifapentine (RPT) Among Infants | Cord blood concentrations were summarized using using R (version 3.5.1). | All infants with available concentration data born to women on the study | Posted | | Mean | Inter-Quartile Range | mcg/mL | | at delivery - (within 3 days of life for infants) | | | | ID | Title | Description |
|---|
| OG000 | All Cohorts | Combined for all infants born to women in Second and Third Trimester of pregnancy |
| | |
| Secondary | Plasma Concentrations of Rifapentine (RPT) Among Infants | Plasma concentrations were summarized using using R (version 3.5.1). | All infants with available concentrations born to women on the study | Posted | | Mean | Inter-Quartile Range | mcg/mL | | at delivery - (within 3 days of life for infants). | | | | ID | Title | Description |
|---|
| OG000 | All Cohorts | Combined for all infants born to women in Second and Third Trimester of pregnancy |
| | |
| Secondary | Cord Blood Concentrations of Desacetyl Rifapentine (Des-RPT) Among Infants | Cord blood concentrations were summarized using using R (version 3.5.1). | All infants with available concentrations born to women on the study | Posted | | Mean | Inter-Quartile Range | mcg/mL | | at delivery (within 3 days of life for infants). | | | | ID | Title | Description |
|---|
| OG000 | All Cohorts | Combined for all infants born to women in Second and Third Trimester of pregnancy |
| | |
| Secondary | Plasma Concentrations of Desacetyl Rifapentine (Des-RPT) Among Infants | Plasma blood concentrations were summarized using using R (version 3.5.1). | All infants with available concentrations born to women on the study | Posted | | Mean | Inter-Quartile Range | mcg/mL | | at delivery - (within 3 days of life for infants). | | | | ID | Title | Description |
|---|
| OG000 | All Cohorts | Combined for all infants born to women in Second and Third Trimester of pregnancy |
| | |
| Secondary | 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. | All participants enrolled on the study | Posted | | Count of Participants | | Participants | | Measured from study entry through participants' last study visit at 24 weeks after delivery | | | | ID | Title | Description |
|---|
| OG000 | Cohort 1 (Pregnant Women Enrolled in the Second Trimester) | 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. | | OG001 | Cohort 2 (Pregnant Women Enrolled in the Third Trimester) | 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. |
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| Secondary | 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. | All participants enrolled on the study | Posted | | Count of Participants | | Participants | | Measured from study entry through participants' last study visit at 24 weeks after delivery | | | | ID | Title | Description |
|---|
| OG000 | Cohort 1 (Pregnant Women Enrolled in the Second Trimester) | 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. | | OG001 | Cohort 2 (Pregnant Women Enrolled in the Third Trimester) | 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. |
| |
| Secondary | 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. | All live born infants enrolled on the study | Posted | | Count of Participants | | Participants | | Measured from birth through participants' last study visit at 24 weeks after delivery | | | | ID | Title | Description |
|---|
| OG000 | Cohort 1(Infants Born to Women Enrolled in Second Trimester) | 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. | | OG001 | Cohort 2 (Infants Born to Women Enrolled in Third Trimester) | Participants will receive 12 directly observed once-weekly doses of RPT, INH, and pyridoxine (vitamin B6) at study entry and at 11 weekly follow-up visits. |
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| Secondary | 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)
| All participants with intensive and sparse PK results at all doses in all stages of pregnancy were used for analysis Note: the mean reported below is actually the value obtained from a population analysis and represents a population estimate with relative standard error | Posted | | Mean | Standard Error | L/hr | | 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). | | | | ID | Title | Description |
|---|
| OG000 | All Cohorts | All participants with intensive and sparse PK results at all doses in all stages of pregnancy were used for analysis |
| |
| Secondary | 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 | All participants with intensive and sparse PK results at all doses in all stages of pregnancy were used for analysis Note: the mean reported below is actually the value obtained from a population analysis and represents a population estimate with relative standard error | Posted | | Mean | Standard Error | hr-1 | | 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). | | | | ID | Title | Description |
|---|
| OG000 | All Cohorts | All participants with intensive and sparse PK results at all doses in all stages of pregnancy were used for analysis |
| |
| Secondary | 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 | All participants with intensive and sparse PK results at all doses in all stages of pregnancy were used for analysis Note: the mean reported below is actually the value obtained from a population analysis and represents a population estimate with relative standard error | Posted | | Mean | Standard Error | L | | 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). | | | | ID | Title | Description |
|---|
| OG000 | All Cohorts | All participants with intensive and sparse PK results at all doses in all stages of pregnancy were used for analysis |
| |