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Evaluating PK, Tolerability, and Safety of Rifapentine and Isoniazid in Pregnant and Postpartum Women

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02651259
Recruitment Status : Completed
First Posted : January 8, 2016
Results First Posted : April 20, 2020
Last Update Posted : May 19, 2020
Sponsor:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)

Tracking Information
First Submitted Date  ICMJE January 7, 2016
First Posted Date  ICMJE January 8, 2016
Results First Submitted Date  ICMJE April 3, 2020
Results First Posted Date  ICMJE April 20, 2020
Last Update Posted Date May 19, 2020
Actual Study Start Date  ICMJE March 13, 2017
Actual Primary Completion Date April 10, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 5, 2020)
  • Clearance Relative to Bioavailability (CL/F) for Rifapentine (RPT) for Intensive and Sparse PK [ 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). ]
    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)
  • Clearance Relative to Bioavailability (CLmet/F) for Desacetyl Rifapentine (Des-RPT) [ 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). ]
    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
  • Absorption Rate Constant (ka) for Rifapentine (RPT) [ 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). ]
    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
  • Volume of Distribution Relative to Bioavailability (Vc/F) for Rifapentine (RPT) [ 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). ]
    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
  • Incidence of Related Serious Adverse Events (SAEs) in Pregnant and Postpartum Women Taking Once-weekly RPT + INH [ Time Frame: Measured from entry through participants' last study visit at 24 weeks after delivery ]
    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.
  • Percentage of Participants With Grade 2 Adverse Events (AEs) Judged to be Related to Study Drug Regimen [ Time Frame: Measured from study entry through participants' last study visit at 24 weeks after delivery ]
    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.
  • Percentage of Participants With All Grade 3 and 4 AEs [ Time Frame: Measured from study entry through participants' last study visit at 24 weeks after delivery ]
    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.
  • Percentage of Participants With All Serious AEs [ Time Frame: Measured from study entry through participants' last study visit at 24 weeks after delivery ]
    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.
  • Percentage of Participants With All AEs Leading to Permanent Discontinuation of Study Drug Regimen (i.e., RPT, INH, and Pyridoxine) [ Time Frame: Measured from study entry through participants' last study treatment dispensation (approximately for 12 weeks) ]
    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.
  • Percentage of Participants With Related Serious Adverse Events (AEs) in Infants Born to Women Taking Once-weekly RPT + INH [ Time Frame: Measured from birth through infants' last study visit at 24 weeks after birth ]
    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.
Original Primary Outcome Measures  ICMJE
 (submitted: January 7, 2016)
  • Composite of clearance (CL/F), absorption, and volume of distribution of RPT and its desacetyl-rifapentine metabolite (desRPT) [ Time Frame: Measured through participants' last study visit at 24 weeks after delivery ]
  • Incidence of Related Serious Adverse Events (SAEs) in Pregnant and Postpartum Women Taking Once-weekly RPT + INH [ Time Frame: Measured through participants' last study visit at 24 weeks after delivery ]
  • Incidence of Grade 2 adverse events (AEs) judged to be related to study drug regimen [ Time Frame: Measured through participants' last study visit at 24 weeks after delivery ]
  • Incidence of all Grade 3 and 4 AEs [ Time Frame: Measured through participants' last study visit at 24 weeks after delivery ]
  • Incidence of all serious AEs [ Time Frame: Measured through participants' last study visit at 24 weeks after delivery ]
  • Incidence of all AEs leading to permanent discontinuation of study drug regimen (i.e., RPT, INH, and pyridoxine) [ Time Frame: Measured through participants' last study visit at 24 weeks after delivery ]
  • Incidence of related serious adverse events (AEs) in infants born to women taking once-weekly RPT + INH [ Time Frame: Measured through infants' last study visit at 24 weeks after birth ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 22, 2020)
  • Clearance Relative to Bioavailability (CL/F) for Rifapentine (RPT) [ 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). ]
    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
  • 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 [ 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). ]
    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
  • Maximum Concentration (Cmax) for RPT Maximum Concentration (Cmax) for Des-RPT Pregnant Women in 2nd and 3rd Trimester [ 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). ]
    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
  • Maximum Concentration (Cmin) for RPT and Maximum Concentration (Cmin) for Des-RPT Pregnant Women in 2nd and 3rd Trimester [ 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). ]
    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
  • Cord Blood Concentrations of Rifapentine (RPT) Among Infants [ Time Frame: at delivery - (within 3 days of life for infants) ]
    Cord blood concentrations were summarized using using R (version 3.5.1).
  • Plasma Concentrations of Rifapentine (RPT) Among Infants [ Time Frame: at delivery - (within 3 days of life for infants). ]
    Plasma concentrations were summarized using using R (version 3.5.1).
  • Cord Blood Concentrations of Desacetyl Rifapentine (Des-RPT) Among Infants [ Time Frame: at delivery (within 3 days of life for infants). ]
    Cord blood concentrations were summarized using using R (version 3.5.1).
  • Plasma Concentrations of Desacetyl Rifapentine (Des-RPT) Among Infants [ Time Frame: at delivery - (within 3 days of life for infants). ]
    Plasma blood concentrations were summarized using using R (version 3.5.1).
  • Number of Participants With Discontinuation of Study Drug Due to Intolerance (Tolerability of Study Drug Regimen - i.e., RPT, INH, and Pyridoxine) [ Time Frame: Measured from study entry through participants' last study visit at 24 weeks after delivery ]
    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.
  • Number of Mothers With Active TB up to 24 Weeks Postpartum [ Time Frame: Measured from study entry through participants' last study visit at 24 weeks after delivery ]
    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.
  • Number of Infants With Active TB up to 24 Weeks of Life [ Time Frame: Measured from birth through participants' last study visit at 24 weeks after delivery ]
    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.
  • Clearance (CL/F) of INH [ 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). ]
    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)
  • Absorption (ka) of INH [ 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). ]
    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
  • Volume of Distribution of INH [ 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). ]
    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
Original Secondary Outcome Measures  ICMJE
 (submitted: January 7, 2016)
  • Composite of Vd, CL/F, Ka for pregnant women in their second or third trimester [ Time Frame: Measured through participants' last study visit at 24 weeks after delivery ]
  • RPT concentrations in infants born to women receiving once-weekly RPT + INH [ Time Frame: Measured through infants' last study visit at 24 weeks after birth ]
  • desRPT concentrations in infants born to women receiving once-weekly RPT + INH [ Time Frame: Measured through infants' last study visit at 24 weeks after birth ]
  • Permanent discontinuation of study drug regimen (i.e., RPT, INH, and pyridoxine) [ Time Frame: Measured through participants' last study visit at 24 weeks after delivery ]
  • Incidence of all AEs leading to permanent discontinuation of study drug regimen (i.e., RPT, INH, and pyridoxine) [ Time Frame: Measured through participants' last study visit at 24 weeks after delivery ]
  • RPT concentrations in breast milk of postpartum women receiving once-weekly RPT + INH [ Time Frame: Measured through participants' last study visit at 24 weeks after delivery ]
  • des-RPT concentrations in breast milk of postpartum women receiving once-weekly RPT + INH [ Time Frame: Measured through participants' last study visit at 24 weeks after delivery ]
  • Incidence of active TB in mother-infant pairs up to 24 weeks postpartum [ Time Frame: Measured through participants' last study visit at 24 weeks after delivery ]
  • Composite of CL/F, absorption, and volume of distribution of INH [ Time Frame: Measured through participants' last study visit at 24 weeks after delivery ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Evaluating PK, Tolerability, and Safety of Rifapentine and Isoniazid in Pregnant and Postpartum Women
Official Title  ICMJE A Phase I/II Trial of the Pharmacokinetics, Tolerability, and Safety of Once-Weekly Rifapentine and Isoniazid in HIV-1-infected and HIV-1-uninfected Pregnant and Postpartum Women With Latent Tuberculosis Infection
Brief Summary 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).
Detailed Description

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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Tuberculosis
Intervention  ICMJE
  • Drug: Rifapentine (RPT)
    900 mg of RPT
    Other Name: Rifamycin
  • Drug: Isoniazid (INH)
    900 mg of INH
    Other Name: isonicotinyl hydrazine,
  • Dietary Supplement: Pyridoxine (vitamin B6)
    25 mg to 100 mg of pyridoxine, based on the current local, national, or international dosing guidelines.
    Other Name: Vitamin B6
Study Arms  ICMJE
  • Experimental: 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.
    Interventions:
    • Drug: Rifapentine (RPT)
    • Drug: Isoniazid (INH)
    • Dietary Supplement: Pyridoxine (vitamin B6)
  • Experimental: 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.
    Interventions:
    • Drug: Rifapentine (RPT)
    • Drug: Isoniazid (INH)
    • Dietary Supplement: Pyridoxine (vitamin B6)
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: April 29, 2019)
50
Original Estimated Enrollment  ICMJE
 (submitted: January 7, 2016)
82
Actual Study Completion Date  ICMJE April 10, 2019
Actual Primary Completion Date April 10, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Age greater than or equal to 18 years, or minimum age of consent according to locally applicable laws or regulations at screening, verified per site standard operating procedures (SOPs); and able and willing to provide written informed consent for study at screening
  • At screening, evidence by ultrasound of a viable singleton pregnancy with an estimated gestational age at enrollment of greater than or equal to 14 weeks through less than or equal to 34 weeks as per screening ultrasound (see protocol for more information)
  • Had at least one of the following risk factors for TB:

    • Per participant report, the participant was a household contact (see NOTE below) of a known active pulmonary TB patient
    • Per medical records, confirmation of HIV-1 infection (see protocol for more information) and a single positive tuberculin skin test (TST) or interferon gamma release assay (IGRA) at any time in the past. If not available in medical record, perform at screening.

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.

  • Documentation of HIV-1 infection status, or confirmation of HIV-1 infection status (if unknown or undocumented). Confirmation of HIV-1 infection was defined as positive results from two samples (described in the protocol) collected at different time points. All samples tested must be whole blood, serum, or plasma. As this study was being conducted under an IND, all test methods should be FDA-approved, if available. If FDA-approved methods were not available, test methods should be verified according to Good Clinical Laboratory Practice (GCLP) and approved by the IMPAACT Laboratory Center. More information on this criterion was available in the protocol.
  • If HIV-1-infected, documented current prescription of efavirenz (EFV) + 2 nucleoside reverse transcriptase inhibitor (NRTI) regimen and reported taking regimen for at least two weeks prior to enrollment (regimens containing protease, integrase, or entry inhibitors were not permitted)
  • Documented laboratory values obtained within 14 days prior to enrollment:

    • Hemoglobin greater than or equal to 7.5 g/dL
    • White blood cell count greater than or equal to 1500 cells/mm^3
    • Alanine transaminase (ALT) less than 2.5 times the upper limit of normal (ULN)
    • Total bilirubin less than 1.6 times the ULN
    • Absolute neutrophil count (ANC) greater than or equal to 750 cells/mm^3
    • Platelet count greater than or equal to 100,000/mm^3
  • Per participant report at screening, intent to remain in the current geographical area of residence for the duration of the study
  • Per participant report at screening, able to swallow whole tablets
  • Per participant report, intention to keep the pregnancy
  • Per participant report, willingness to permit infant to participate in the study

Exclusion Criteria:

  • Evidence of confirmed or probable active TB disease per World Health Organization (WHO) symptom screen and confirmation by Gene Xpert, shielded chest x-ray, or sputum sample
  • Participant report of personal history of INH- or rifampin-resistant, multi-drug resistant (MDR), or extensively drug-resistant (XDR) TB
  • Participant report of personal history of active TB in the past 2 years
  • Participant report of previous treatment for latent tuberculosis infection (LTBI)
  • Household contact (as defined above) with known active MDR or XDR TB disease
  • Known major fetal abnormality as detected on ultrasound
  • Known allergy/sensitivity or any hypersensitivity to components of study drugs or their formulation
  • Known history of liver cirrhosis at any time prior to study entry
  • Per participant report and/or medical records, evidence of acute clinical hepatitis, such as a combination of abdominal pain, jaundice, dark urine, and/or light stools within 90 days prior to entry
  • Participant report and/or medical records of peripheral neuropathy Grade 2 or higher within 90 days prior to entry
  • Current use or history of active drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements
  • Participant report and/or clinical evidence of porphyria
  • Any other condition that, in the opinion of the investigator of record (IoR)/designee, would preclude informed consent, make study participation unsafe, complicate interpretation of study outcome data, or otherwise interfere with achieving the study objectives, including taking the study medication
  • Planned or current participation in an interventional drug study
  • Current use of any prohibited or precautionary medications (see protocol for more information), including didanosine (DDI) or stavudine (D4T)
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Haiti,   Kenya,   Malawi,   Thailand,   Zimbabwe
Removed Location Countries United States
 
Administrative Information
NCT Number  ICMJE NCT02651259
Other Study ID Numbers  ICMJE IMPAACT 2001
12026 ( Registry Identifier: DAIDS-ES )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party National Institute of Allergy and Infectious Diseases (NIAID)
Study Sponsor  ICMJE National Institute of Allergy and Infectious Diseases (NIAID)
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Chair: Jyoti S. Mathad, MD, MSc Weill Medical College of Cornell University
PRS Account National Institute of Allergy and Infectious Diseases (NIAID)
Verification Date May 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP