Ignite Creation Date:
2024-05-05 @ 10:17 AM
Last Modification Date:
2024-10-26 @ 9:05 AM
Study NCT ID:
NCT00006604
Status:
COMPLETED
Last Update Posted:
2021-11-05
First Post:
2000-12-06
Brief Title:
Atazanavir Used in Combination With Other Anti-HIV Drugs in HIV-Infected Infants Children and Adolescents
Sponsor:
National Institute of Allergy and Infectious Diseases NIAID
Organization:
National Institute of Allergy and Infectious Diseases NIAID
Study Overview
Official Title:
Phase III Open-Label Pharmacokinetic and Safety Study of a Novel Protease Inhibitor BMS 232632 Atazanavir ATV Reyataz in Combination Regimens in Antiretroviral Therapy ART-Naive and -Experienced HIV-Infected Infants Children and Adolescents
Status:
COMPLETED
Status Verified Date:
2016-03
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:
The purpose of this study was to find a safe and tolerable dose of the protease inhibitor PI atazanavir ATV with or without a low-dose boost of the PI ritonavir RTV when taken with other anti-HIV drugs in HIV infected infants children and adolescents
Advancements in anti-HIV drugs for HIV infected children and adolescents have been hard to make in part because these patients often do not take the drugs as prescribed ATV may be a better option because it is available in the form of powder which children and adolescents may be more willing to take regularly Using a low dose of RTV as a boosting agent for ATV may also increase the chances of virologic response of highly active antiretroviral treatment HAART-experienced patients This study aimed to find safe and tolerable doses of ATV with or without low-dose RTV boost in infants children and adolescents For this study participants were enrolled in the United States and South Africa
Advancements in anti-HIV drugs for HIV infected children and adolescents have been hard to make in part because these patients often do not take the drugs as prescribed ATV may be a better option because it is available in the form of powder which children and adolescents may be more willing to take regularly Using a low dose of RTV as a boosting agent for ATV may also increase the chances of virologic response of highly active antiretroviral treatment HAART-experienced patients This study aimed to find safe and tolerable doses of ATV with or without low-dose RTV boost in infants children and adolescents For this study participants were enrolled in the United States and South Africa
Detailed Description:
Advancements in HAART for HIV-infected children and adolescents are hindered by patient nonadherence The availability of a powder formulation and the once-daily dosing schedule make ATV an attractive agent for improved adherence in pediatric treatment regimens This study was designed to provide pharmacokinetic PK data to guide dosing recommendations for ATV when given concurrently with or without low-dose RTV boost in infants children and adolescents During the study the safety and tolerance of ATV with or without low-dose RTV were closely monitored and virologic efficacy data were obtained
There were two parts to this study Step I took place in the United States and South Africa and were further divided into two sets of groups Parts A and B Part A participants received ATV only and Part B participants received ATV with low-dose RTV boost All participants received ATV once a day with 2 other antiretroviral drugs not provided by the study In Part B only participants received ATV with a low dose of RTV Participants were placed into 1 of 8 groups Groups 1 to 4 for Part A Groups 5 to 8 for Part B with respect to age and study drug formulation Participants in Groups 1 and 5 were infants between ages 3 months and 1 day 91 days and 2 years less than or exactly 730 days and took ATV in powder form Participants in Groups 2 3 6 and 7 were children between 2 years and 1 day 731 days old and 13 years old Groups 2 and 6 received ATV in powder form while Groups 3 and 7 received the capsule form Patients in Groups 4 and 8 were adolescents between 13 years and 1 day old and 21 years old not including the 22nd birthday and took ATV in capsule form As of 01022008 a new group 5A was opened for enrollment Participants in Group 5A were between 3 months and 6 months old and took ATV in powder form plus a low-dose RTV booster
For each group enrollment started with five participants per group All participants were evaluated for PK and safety criteria adjusting the dose of ATV until one was found that passes both sets of criteria Then five additional participants were enrolled with enrollment continuing for each group once all participants within that group meet the PK criteria For groups receiving RTV Groups 5 to 8 additional criteria must be met for each dose of ATV studied In addition to the PK and safety evaluations 24-hour post-dose concentrations Cmin were monitored in the first 10 participants enrolled for a dose of ATV before more participants were enrolled and studied at that same dose Note that in Protocol Version 50 South African SA sites were allowed to enroll patients in study groups 345678 As a result the study design has been modified to further stratify study groups 3 4 5 6 7 8 at the final recommended dose by country ie USA versus SA such that 10 evaluable study subjects will be accrued in parallel to each study group-country cohort
Clinic visits will be every 4 weeks through Week 48 then every 8 weeks until the last participant to enroll in the study has reached Week 96 of hisher treatment If after 56 weeks a participant has a toxic reaction to a nucleosidetide reverse transcriptase inhibitor NRTI in their medication regimen the regimen may be changed to a different NRTI At every visit participants will undergo a complete medical history and physical exam cardiac conduction evaluation and urine and blood collection Participants of childbearing age will have a pregnancy test performed at each visit
Step II will only be open to South African subjects who are virologically responding to treatment when the last enrollee into either part of Step I Part A or Part B has completed 96 weeks of treatment end of Step I All such participants will be given ATV in capsule form at the same dose they received at the end of Step I as well as the other antiretrovirals they were receiving during Step I Step II will continue until ATV is approved in South Africa and readily available by individual prescription and participants will have a study visit every 12 weeks
Note that the following ATV doses were independently evaluated for each group during the dose-finding stage based on the description above Group 1 ATV Powder 310mgm2 620mgm2 Group 2 ATV Powder 310mgm2 620mgm2 Group 3 ATV Capsule 310mgm2 415mgm2 520mgm2 Group 4 ATV Capsule 310mgm2 520mgm2 620mgm2 Group 5 ATV Powder RTV 310mgm2 Group 6 ATV Powder RTV 310mgm2 Group 7 ATV Capsule RTV 310mgm2 205mgm2 Group 8 ATV Capsule RTV 310mgm2 205mgm2 Group 5A ATV Powder RTV 310mgm2 All these dosing groups are presented in Participant Flow groups to show the total number of participants enrolled but only the participants enrolled at the final group doses are presented in the subsequent results
The following groups satisfied the safety and PK guidelines specified in the protocol Groups 34678 Groups 5 and 5A did not satisfy the protocol-defined pharmacokinetic criteria There was considerable inter-subject variability in systemic exposures in this age group such that a dose escalation to 415mgm2 may have resulted in ATV exposures greater than 90000 nghrmL in some children Thus a further dose increase in Groups 5 and 5A was not attempted
These are the final dose for each group Groups 1 and 2 Final dose was not established Group 3 ATV Capsule 520mgm2 Group 4 ATV Capsule 620mgm2 Group 5 ATV Powder 310mgm2 RTV Group 6 ATV Powder 310mgm2 RTV Group 7 ATV Capsule 205mgm2 RTV Group 8 ATV Capsule 205mgm2 RTV Group 5A ATV Powder 310mgm2 RTV
There were two parts to this study Step I took place in the United States and South Africa and were further divided into two sets of groups Parts A and B Part A participants received ATV only and Part B participants received ATV with low-dose RTV boost All participants received ATV once a day with 2 other antiretroviral drugs not provided by the study In Part B only participants received ATV with a low dose of RTV Participants were placed into 1 of 8 groups Groups 1 to 4 for Part A Groups 5 to 8 for Part B with respect to age and study drug formulation Participants in Groups 1 and 5 were infants between ages 3 months and 1 day 91 days and 2 years less than or exactly 730 days and took ATV in powder form Participants in Groups 2 3 6 and 7 were children between 2 years and 1 day 731 days old and 13 years old Groups 2 and 6 received ATV in powder form while Groups 3 and 7 received the capsule form Patients in Groups 4 and 8 were adolescents between 13 years and 1 day old and 21 years old not including the 22nd birthday and took ATV in capsule form As of 01022008 a new group 5A was opened for enrollment Participants in Group 5A were between 3 months and 6 months old and took ATV in powder form plus a low-dose RTV booster
For each group enrollment started with five participants per group All participants were evaluated for PK and safety criteria adjusting the dose of ATV until one was found that passes both sets of criteria Then five additional participants were enrolled with enrollment continuing for each group once all participants within that group meet the PK criteria For groups receiving RTV Groups 5 to 8 additional criteria must be met for each dose of ATV studied In addition to the PK and safety evaluations 24-hour post-dose concentrations Cmin were monitored in the first 10 participants enrolled for a dose of ATV before more participants were enrolled and studied at that same dose Note that in Protocol Version 50 South African SA sites were allowed to enroll patients in study groups 345678 As a result the study design has been modified to further stratify study groups 3 4 5 6 7 8 at the final recommended dose by country ie USA versus SA such that 10 evaluable study subjects will be accrued in parallel to each study group-country cohort
Clinic visits will be every 4 weeks through Week 48 then every 8 weeks until the last participant to enroll in the study has reached Week 96 of hisher treatment If after 56 weeks a participant has a toxic reaction to a nucleosidetide reverse transcriptase inhibitor NRTI in their medication regimen the regimen may be changed to a different NRTI At every visit participants will undergo a complete medical history and physical exam cardiac conduction evaluation and urine and blood collection Participants of childbearing age will have a pregnancy test performed at each visit
Step II will only be open to South African subjects who are virologically responding to treatment when the last enrollee into either part of Step I Part A or Part B has completed 96 weeks of treatment end of Step I All such participants will be given ATV in capsule form at the same dose they received at the end of Step I as well as the other antiretrovirals they were receiving during Step I Step II will continue until ATV is approved in South Africa and readily available by individual prescription and participants will have a study visit every 12 weeks
Note that the following ATV doses were independently evaluated for each group during the dose-finding stage based on the description above Group 1 ATV Powder 310mgm2 620mgm2 Group 2 ATV Powder 310mgm2 620mgm2 Group 3 ATV Capsule 310mgm2 415mgm2 520mgm2 Group 4 ATV Capsule 310mgm2 520mgm2 620mgm2 Group 5 ATV Powder RTV 310mgm2 Group 6 ATV Powder RTV 310mgm2 Group 7 ATV Capsule RTV 310mgm2 205mgm2 Group 8 ATV Capsule RTV 310mgm2 205mgm2 Group 5A ATV Powder RTV 310mgm2 All these dosing groups are presented in Participant Flow groups to show the total number of participants enrolled but only the participants enrolled at the final group doses are presented in the subsequent results
The following groups satisfied the safety and PK guidelines specified in the protocol Groups 34678 Groups 5 and 5A did not satisfy the protocol-defined pharmacokinetic criteria There was considerable inter-subject variability in systemic exposures in this age group such that a dose escalation to 415mgm2 may have resulted in ATV exposures greater than 90000 nghrmL in some children Thus a further dose increase in Groups 5 and 5A was not attempted
These are the final dose for each group Groups 1 and 2 Final dose was not established Group 3 ATV Capsule 520mgm2 Group 4 ATV Capsule 620mgm2 Group 5 ATV Powder 310mgm2 RTV Group 6 ATV Powder 310mgm2 RTV Group 7 ATV Capsule 205mgm2 RTV Group 8 ATV Capsule 205mgm2 RTV Group 5A ATV Powder 310mgm2 RTV
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 |
|---|---|---|---|
| ACTG P1020-A | Registry Identifier | DAIDS ES | None |
| 10037 | REGISTRY | None | None |
| IMPAACT P1020A | None | None | None |
| PACTG P1020-A | None | None | None |