Ignite Creation Date:
2024-05-05 @ 5:34 PM
Last Modification Date:
2024-10-26 @ 9:33 AM
Study NCT ID:
NCT00485264
Status:
COMPLETED
Last Update Posted:
2021-11-02
First Post:
2007-06-11
Brief Title:
Safety and Pharmacokinetics PK of Raltegravir in HIV Human Immunodeficiency Virus-Infected 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:
A Phase III Multicenter Open-Label Noncomparative Study of the International Maternal Pediatric Adolescent AIDS Clinical Trials IMPAACT Group to Evaluate the Safety Tolerability Pharmacokinetics and Antiviral Activity of Raltegravir Isentress MK-0518 in HIV-1 Infected Children and Adolescents
Status:
COMPLETED
Status Verified Date:
2021-10
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:
Integrase is 1 of 3 HIV Human Immunodeficiency Virus-1 enzymes required for viral replication Raltegravir is a drug that prevents integrase from working properly This drug has been tested for safety and efficacy in adults but this is the first study to examine raltegravir in children and adolescents The purpose of this study was to determine the appropriate dose for raltegravir across the pediatric age range from 4 weeks to 18 years of age by acquiring short and long term safety data intensive and population pharmacokinetic PK data and efficacy experience with raltegravir in HIV-infected children and adolescents
Detailed Description:
Integrase is one of three enzymes necessary for HIV replication Integrase allows for the integration of HIV DNA deoxyribonucleic acid into the human genome Raltegravir is a strong and selective inhibitor of HIV integrase In adults raltegravir has shown significant antiretroviral activity in clinical trials and is well tolerated The purpose of this study was to determine the appropriate dose for raltegravir across the pediatric age range from 4 weeks 30 days to 18 years of age by acquiring short and long term safety data intensive and population PK data and efficacy experience with raltegravir in treatment-experienced HIV-infected children and adolescents
The study consisted of two sequential Stages I and II The dose finding period of Stage I was intended to examine the pharmacokinetics and short term tolerability and safety of raltegravir in a limited number of participants to permit dose selection for further study in Stage II The dose finding algorithm required a preliminary assessment of data from the first 4 patients of each cohort termed a mini-cohort Failure to meet PK targets required dose adjustments contingent upon the mini-cohorts dose having met safety criteria followed by reassessment of safety and PK data from the new mini-cohort dose When a mini-cohort dose had passed both safety and PK criteria further accrual to and an assessment of results from the full cohort could occur Again failure to meet PK targets required dose adjustments contingent upon the full cohorts dose having met safety criteria with subsequent PK and safety evaluation of data from a new cohort taking the new dose
Chronic dosing which includes Stage I extension the period after Stage I dose finding and Stage II additional participants enrolled was intended to provide longer term safety and antiviral activity data in a larger sample of participants Participants accrued into Stage I and treated only at the dose ultimately selected for their cohorts were combined with those accrued into Stage II where all patients received only the final selected doses for their respective cohorts This group is denoted as the Final Dose Population and results from this group are considered primary since they reflect only the age-specific doses proposed for commercial use The group with all participants exposed to raltegravir at any dose is denoted as the All Treated Population
Stage I lasted for a minimum of 48 weeks Stage II was for 48 weeks and a long-term follow-up period lasted for 5 years from initial exposure ie 48 weeks of treatment plus 4 years of follow-up Participants were stratified by age and assigned to one of six cohorts Participants in Cohort I were between the ages of 12 and 18 years and received poloxamer film coated raltegravir tablets Participants in Cohort IIA were between the ages of 6 and 11 years weighed at least 25 kg and received poloxamer film coated raltegravir tablets Participants in Cohort IIB were between the ages of 6 and 11 years and received chewable raltegravir tablets Participants in Cohort III were between the ages of 2 and 5 years and received chewable raltegravir tablets Participants in Cohort IV were between the ages of 6 months defined as 180 days and 23 months and received oral granules for suspension Participants in Cohort V were between the ages of 4 weeks defined as 30 days and 5 months and received oral granules for suspension
Enrollment for Stage I of this study began with Cohort I and progressed to the other cohorts once preliminary dosage had been determined and safety data were reviewed When this information had been determined for Cohort I Cohorts IIA and IIB began enrollment Once safety and dose data for these cohorts were reviewed enrollment into Cohort III began Once safety and dose data for Cohort III were reviewed enrollment into Cohort IV began and once safety and dose data for Cohort IV were reviewed enrollment into Cohort V began
During Stage II of this study participants took raltegravir at the dosage determined as safe and reaching PK targets based on the the Stage I data The purpose of Stage II was to determine long-term safety of raltegravir once a safe dose meeting PK targets has been determined
Participants whose Stage I dose was different from the dose determined for Stage II and who had not had individual dose adjustments because of extreme PK values had their raltegravir dose changed to the selected Stage II dose once it was determined If individualizing the dose for participants in this manner resulted in a dose increase these participants had an additional safety visit 4 weeks after the dose modification and then continued on study visits with no further changes in the visit schedule
There were at least 9 study visits for participants in this study occurring during the 48-week raltegravir treatment period For participants who completed 48 weeks of study and appeared to have benefited from receiving study drug raltegravir was provided until five years after initial raltegravir exposure For participants who opted to continue on study-provided raltegravir extended provision of drug was implemented as part of a protocol extension involving visits every 4 months for five years after initial raltegravir exposure Participants who did not continue on study-provided raltegravir were followed with annual visits for five years after initial raltegravir exposure ie 48 weeks of raltegravir treatment plus 4 years follow-up At each visit a physical exam blood collection and determination of treatment adherence occurred At some visits urine collection and Tanner staging occurred Selected cohorts underwent a taste evaluation at 1 of 2 visits Participants aged 2 to less than 6 years of age were asked to participate in an additional PK substudy in which blood was collected two times over a 12-hour visit or if more convenient this assessment may have been completed in 2 separate visits in order to collect additional Cmin PK data Participants were re-registered into the same cohort if a dose change was recommended
Current pediatric Food and Drug Administration approval and dosing recommendations are based upon evaluations in 122 Final Dose participants aged 4 weeks to 18 years enrolled in this study
The results present safety and efficacy results of the complete 5 year follow up data primary and key secondary endpoints of the participants from IMPAACT P1066 the Final Dose Population By the date on which most of the data were frozen 24 July 2017 all participants enrolled had Week 24 data ie had either completed the Week 24 visit or for those who discontinued before Week 24 had the potential to have experienced the Week 24 visit had also completed or had the potential to have experienced the Week 48 visit and had either completed 240 weeks of study and were subsequently taken off study or had prematurely discontinued study and were no longer in follow up
The study consisted of two sequential Stages I and II The dose finding period of Stage I was intended to examine the pharmacokinetics and short term tolerability and safety of raltegravir in a limited number of participants to permit dose selection for further study in Stage II The dose finding algorithm required a preliminary assessment of data from the first 4 patients of each cohort termed a mini-cohort Failure to meet PK targets required dose adjustments contingent upon the mini-cohorts dose having met safety criteria followed by reassessment of safety and PK data from the new mini-cohort dose When a mini-cohort dose had passed both safety and PK criteria further accrual to and an assessment of results from the full cohort could occur Again failure to meet PK targets required dose adjustments contingent upon the full cohorts dose having met safety criteria with subsequent PK and safety evaluation of data from a new cohort taking the new dose
Chronic dosing which includes Stage I extension the period after Stage I dose finding and Stage II additional participants enrolled was intended to provide longer term safety and antiviral activity data in a larger sample of participants Participants accrued into Stage I and treated only at the dose ultimately selected for their cohorts were combined with those accrued into Stage II where all patients received only the final selected doses for their respective cohorts This group is denoted as the Final Dose Population and results from this group are considered primary since they reflect only the age-specific doses proposed for commercial use The group with all participants exposed to raltegravir at any dose is denoted as the All Treated Population
Stage I lasted for a minimum of 48 weeks Stage II was for 48 weeks and a long-term follow-up period lasted for 5 years from initial exposure ie 48 weeks of treatment plus 4 years of follow-up Participants were stratified by age and assigned to one of six cohorts Participants in Cohort I were between the ages of 12 and 18 years and received poloxamer film coated raltegravir tablets Participants in Cohort IIA were between the ages of 6 and 11 years weighed at least 25 kg and received poloxamer film coated raltegravir tablets Participants in Cohort IIB were between the ages of 6 and 11 years and received chewable raltegravir tablets Participants in Cohort III were between the ages of 2 and 5 years and received chewable raltegravir tablets Participants in Cohort IV were between the ages of 6 months defined as 180 days and 23 months and received oral granules for suspension Participants in Cohort V were between the ages of 4 weeks defined as 30 days and 5 months and received oral granules for suspension
Enrollment for Stage I of this study began with Cohort I and progressed to the other cohorts once preliminary dosage had been determined and safety data were reviewed When this information had been determined for Cohort I Cohorts IIA and IIB began enrollment Once safety and dose data for these cohorts were reviewed enrollment into Cohort III began Once safety and dose data for Cohort III were reviewed enrollment into Cohort IV began and once safety and dose data for Cohort IV were reviewed enrollment into Cohort V began
During Stage II of this study participants took raltegravir at the dosage determined as safe and reaching PK targets based on the the Stage I data The purpose of Stage II was to determine long-term safety of raltegravir once a safe dose meeting PK targets has been determined
Participants whose Stage I dose was different from the dose determined for Stage II and who had not had individual dose adjustments because of extreme PK values had their raltegravir dose changed to the selected Stage II dose once it was determined If individualizing the dose for participants in this manner resulted in a dose increase these participants had an additional safety visit 4 weeks after the dose modification and then continued on study visits with no further changes in the visit schedule
There were at least 9 study visits for participants in this study occurring during the 48-week raltegravir treatment period For participants who completed 48 weeks of study and appeared to have benefited from receiving study drug raltegravir was provided until five years after initial raltegravir exposure For participants who opted to continue on study-provided raltegravir extended provision of drug was implemented as part of a protocol extension involving visits every 4 months for five years after initial raltegravir exposure Participants who did not continue on study-provided raltegravir were followed with annual visits for five years after initial raltegravir exposure ie 48 weeks of raltegravir treatment plus 4 years follow-up At each visit a physical exam blood collection and determination of treatment adherence occurred At some visits urine collection and Tanner staging occurred Selected cohorts underwent a taste evaluation at 1 of 2 visits Participants aged 2 to less than 6 years of age were asked to participate in an additional PK substudy in which blood was collected two times over a 12-hour visit or if more convenient this assessment may have been completed in 2 separate visits in order to collect additional Cmin PK data Participants were re-registered into the same cohort if a dose change was recommended
Current pediatric Food and Drug Administration approval and dosing recommendations are based upon evaluations in 122 Final Dose participants aged 4 weeks to 18 years enrolled in this study
The results present safety and efficacy results of the complete 5 year follow up data primary and key secondary endpoints of the participants from IMPAACT P1066 the Final Dose Population By the date on which most of the data were frozen 24 July 2017 all participants enrolled had Week 24 data ie had either completed the Week 24 visit or for those who discontinued before Week 24 had the potential to have experienced the Week 24 visit had also completed or had the potential to have experienced the Week 48 visit and had either completed 240 weeks of study and were subsequently taken off study or had prematurely discontinued study and were no longer in follow up
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 P1066 | OTHER | IMPAACT | None |
| 10495 | REGISTRY | None | None |