Ignite Creation Date:
2024-05-05 @ 11:27 AM
Last Modification Date:
2024-10-26 @ 9:07 AM
Study NCT ID:
NCT00042289
Status:
COMPLETED
Last Update Posted:
2022-07-22
First Post:
2002-07-26
Brief Title:
Pharmacokinetic Study of Antiretroviral Drugs and Related Drugs During and After Pregnancy
Sponsor:
National Institute of Allergy and Infectious Diseases NIAID
Organization:
National Institute of Allergy and Infectious Diseases NIAID
Study Overview
Official Title:
Pharmacokinetic Properties of Antiretroviral and Related Drugs During Pregnancy and Postpartum
Status:
COMPLETED
Status Verified Date:
2022-06
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
IMPAACT P1026s is a Phase IV prospective clinical study to evaluate the pharmacokinetics PKs of antiretroviral ARV and tuberculosis TB medications in pregnant women and their infants Pharmacokinetics are the various interactions between a drug and the body This study also evaluated the PKs of certain ARVs in postpartum women before and after starting hormonal contraceptives The PKs of these drugs were evaluated by measuring the amount of medicine present in blood andor vaginal secretions
Detailed Description:
Pregnant women experience unique physiological changes that may result in clinically significant alterations in drug PKs Unfortunately there have been few clinical trials to study the PKs of ARV TB and hormonal contraceptive drugs in pregnant women The development of appropriate dosing regimens for the HIV-infected pregnant woman is critical to the health of both mother and fetus Overdosing may lead to maternal adverse events and increased risk of fetal toxicity while underdosing may lead to inadequate virologic control increased risk of developing drug resistance mutations and a higher rate of perinatal HIV transmission This study evaluated the PKs of ARVs used during pregnancy the PKs of TB drugs used during pregnancy both in women who are HIV-positive and also taking ARVs and in women who are HIV-negative and not taking ARVs and the PKs of hormonal contraceptive medications taken along with ARVs
P1026s is a Phase IV clinical study Participants were not assigned to the drugs under study but were already receiving the drugs for clinical care by prescription of their clinical care providers They were enrolled into study arms according to the drugs they were receiving through clinical care and if on multiple drugs of interest were able to enroll into multiple arms simultaneously No drugs were provided as part of this study This observational study was added to an existing investigational new drug IND number because several of the drugs were studied at a higher does than the approved dose after the PK results for the approved dose were found to be inadequate
P1026s went through 10 protocol versions with the first and last versions of the protocol finalized in 2002 and 2016 respectively New study arms were added and analyzed separately with each update of the protocol version In general there were five main groups of study arms HIV-infected pregnant women taking ARVs without TB treatment HIV-infected pregnant women taking ARVs with first-line TB treatment HIV-uninfected pregnant women taking no ARVs with first-line TB treatment HIV-infected and HIV-uninfected pregnant women with or without ARVs with second-line TB treatment for drug-resistant TB and HIV-infected postpartum women taking ARVs and hormonal contraceptives The primary analysis of each arm was designed and conducted as a separate single arm evaluation of the drug or combination of drugs of interest
Women who were 20 07 weeks to 37 67 weeks pregnant were enrolled in this study and remained in the study for up to 12 weeks after delivery Postpartum women were enrolled at 2 to 12 weeks after delivery and followed until 6 to 7 weeks after starting contraceptives Infants were enrolled in-utero and followed for 16 to 24 weeks of life At all study visits participants underwent a medical history a physical exam and blood collection At some visits women in some arms underwent a vaginal swab Blood collection from the mother and the detached umbilical cord occurred during delivery Intensive PK sampling was performed at study visits during the second and third trimester of pregnancy andor postpartum depending on the study arm Additional study visits may have occurred depending on the ARV drug regimen prescribed Infant washout PK samples were collected at 2-10 18-28 36-72 hours after birth and 5-9 days of life
There are a total of 49 study arms across all versions of P1026s protocols Out of the 49 study arms 2 did not have PK data didanosine delayed release DDI and lopinavirritonavir LPVRTV African sites only 2 never enrolled any participants amprenavir APV and nevirapinerifampicin NVPRIF with at least one first line TB drug 9 are in the line to be testedanalyzed due to batched analysis which has to be done after the end of the study the lengthy process of development validation and approval regulatory burdens and laboratory delays related to the COVID-19 pandemic all TB arms and all but 3 contraceptive arms atazanavirritonavirtenofovir ATVRTVTFV with etonogestrel ENG efavirenz EFV with ENG and LPVRTV with ENG and 8 had completion dates earlier than December 26 2007 nevirapine NVP abacavir ABC LPVRTV 400100 mg twice daily bid LPVRTV 400100mg then 533133mg bid nelfinavir NFV emtricitabine FTC indinavirritonavir IDVRTV and tipranavirritonavir In this submission the Results Section presents participant flow baseline characteristics and adverse events for all study arms except the 2 arms that never enrolled and outcome measure results for the 28 remaining study arms that have been completed and have final results available For study arms completed prior to December 26 2007 refer to the study publications in the References section for outcome measures
For arms with very low enrollment N3 some results throughout the record eg baseline characteristics and outcome measures were not reported in order to avoid making individual participant data identifiable
In the Outcome Measures section there could be multiple outcome measures for same PK parameters eg AUC12 depending on different units or summary statistics used in the analyses such as median with range vs median with interquartile range IQR
P1026s is a Phase IV clinical study Participants were not assigned to the drugs under study but were already receiving the drugs for clinical care by prescription of their clinical care providers They were enrolled into study arms according to the drugs they were receiving through clinical care and if on multiple drugs of interest were able to enroll into multiple arms simultaneously No drugs were provided as part of this study This observational study was added to an existing investigational new drug IND number because several of the drugs were studied at a higher does than the approved dose after the PK results for the approved dose were found to be inadequate
P1026s went through 10 protocol versions with the first and last versions of the protocol finalized in 2002 and 2016 respectively New study arms were added and analyzed separately with each update of the protocol version In general there were five main groups of study arms HIV-infected pregnant women taking ARVs without TB treatment HIV-infected pregnant women taking ARVs with first-line TB treatment HIV-uninfected pregnant women taking no ARVs with first-line TB treatment HIV-infected and HIV-uninfected pregnant women with or without ARVs with second-line TB treatment for drug-resistant TB and HIV-infected postpartum women taking ARVs and hormonal contraceptives The primary analysis of each arm was designed and conducted as a separate single arm evaluation of the drug or combination of drugs of interest
Women who were 20 07 weeks to 37 67 weeks pregnant were enrolled in this study and remained in the study for up to 12 weeks after delivery Postpartum women were enrolled at 2 to 12 weeks after delivery and followed until 6 to 7 weeks after starting contraceptives Infants were enrolled in-utero and followed for 16 to 24 weeks of life At all study visits participants underwent a medical history a physical exam and blood collection At some visits women in some arms underwent a vaginal swab Blood collection from the mother and the detached umbilical cord occurred during delivery Intensive PK sampling was performed at study visits during the second and third trimester of pregnancy andor postpartum depending on the study arm Additional study visits may have occurred depending on the ARV drug regimen prescribed Infant washout PK samples were collected at 2-10 18-28 36-72 hours after birth and 5-9 days of life
There are a total of 49 study arms across all versions of P1026s protocols Out of the 49 study arms 2 did not have PK data didanosine delayed release DDI and lopinavirritonavir LPVRTV African sites only 2 never enrolled any participants amprenavir APV and nevirapinerifampicin NVPRIF with at least one first line TB drug 9 are in the line to be testedanalyzed due to batched analysis which has to be done after the end of the study the lengthy process of development validation and approval regulatory burdens and laboratory delays related to the COVID-19 pandemic all TB arms and all but 3 contraceptive arms atazanavirritonavirtenofovir ATVRTVTFV with etonogestrel ENG efavirenz EFV with ENG and LPVRTV with ENG and 8 had completion dates earlier than December 26 2007 nevirapine NVP abacavir ABC LPVRTV 400100 mg twice daily bid LPVRTV 400100mg then 533133mg bid nelfinavir NFV emtricitabine FTC indinavirritonavir IDVRTV and tipranavirritonavir In this submission the Results Section presents participant flow baseline characteristics and adverse events for all study arms except the 2 arms that never enrolled and outcome measure results for the 28 remaining study arms that have been completed and have final results available For study arms completed prior to December 26 2007 refer to the study publications in the References section for outcome measures
For arms with very low enrollment N3 some results throughout the record eg baseline characteristics and outcome measures were not reported in order to avoid making individual participant data identifiable
In the Outcome Measures section there could be multiple outcome measures for same PK parameters eg AUC12 depending on different units or summary statistics used in the analyses such as median with range vs median with interquartile range IQR
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| IMPAACT P1026s | Registry Identifier | DAIDS ES | None |
| 10040 | REGISTRY | None | None |