Ignite Creation Date:
2024-05-05 @ 10:00 AM
Last Modification Date:
2024-10-26 @ 9:02 AM
Study NCT ID:
NCT00000893
Status:
COMPLETED
Last Update Posted:
2021-10-29
First Post:
1999-11-02
Brief Title:
Safety Tolerability and Anti-HIV Activity of DMP 266 Efavirenz in Combination With Nelfinavir in HIV-Positive Children
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 Open-Label AUC-Controlled Study to Determine the Pharmacokinetics Safety Tolerability and Antiviral Activity of DMP 266 Efavirenz in Combination With Nelfinavir in Children
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:
Cohort I The purpose of this study is to see how safe it is to combine 2 anti-HIV medications efavirenz EFZ and nelfinavir NFV to treat HIV-positive children and to find an appropriate dose of EFZ to use in combination with NFV Cohort II The purpose of this study is to see how safe it is to give EFZ syrup combined with NFV and to measure the levels of EFZ and NFV in the blood This purpose reflects a change from the original since there are now 2 different cohorts of patients EFZ is an effective anti-HIV medication that easily can be combined with other drugs to treat HIV This is an early study to determine a safe and effective dose for HIV-positive children This study also will examine the correct dose of NFV to use in combination with EFZ
Detailed Description:
The demonstrated antiviral activity tolerability and pharmacokinetic properties of DMP 266 and its utility in combination with other agents make DMP 266 an attractive agent for use in HIV-infected pediatric patients However the tolerability of DMP 266 in the pediatric population must be evaluated and appropriate dosing instructions need to be developed By following the patients over time the antiviral activity of DMP 266-containing regimens will be documented Dosage guidelines for children can then be developed following analysis of the results
This is a 48-week AS PER AMENDMENT APA 122198104-week APA 5800 208-week study It is designed to minimize the chance that ineffective therapy is provided short dose-escalation phase and utilizes an area under the concentration time curve AUC to establish plasma levels of DMP 266 and nelfinavir in the pediatric population that are both tolerable and efficacious APA 52698 Patients are stratified by age into Cohorts I and II and receive EFV concurrently with NFV
APA 52698 The initial starting dose of DMP 266 for patients in Cohort II is higher than the initial starting dose for patients in Cohort I APA 122198 The initial starting dose for patients in Stratum 1 of Cohort II is higher than the initial starting dose for patients in Cohort I and Stratum 2 of Cohort II The initial target AUC for DMP 266 is between 190 and 380 micromolesh uMh The initial starting dose based on a 70 kg patient and adjusted for each patients weight for the first 6 patients is adjusted on the basis of tolerability and plasma concentrations of DMP 266 after 2 weeks of daily doses If at least 4 of the first 6 patients attain a tolerable dose dose at which no more than 2 of 6 patients experience Grade 3 or worse toxicity and target AUC additional patients may continue to be accrued However if any of the initial 6 patients experience life-threatening toxicity further accrual is suspended APA 52698 An assessment of the tolerability and plasma concentrations of EFV is not required in an initial group of Cohort II patients Individual dose is based on pharmacokinetic sampling Patients receive a given starting dose of DMP 266 and continue on that dose until individual dose adjustments are needed If a patients starting dose is tolerated but the target AUC is not achieved the dose is increased If the starting dose is well tolerated and target AUC achieved no adjustment in starting dose is given to future patients If no tolerated dose achieving at least an AUC of 150 micromolesh is reached in 4 of 6 patients the study is suspended and alternative dosing regimens eg twice-daily dosing are considered
A patients current dose of DMP 266 is adjusted based on how the dose is tolerated and whether the target AUC is achieved If a patient does not achieve an AUC of greater than 110 micromolesh and experiences Grade 3 or worse toxicity the patient is discontinued from the study
APA 122198 The dose of NFV is the same for patients in Cohort I and Stratum 2 of Cohort II the dose for patients in Stratum 1 of Cohort II is higher The minimum target AUC for NFV is 10 mg x hL Doses are adjusted for an individual child if AUC falls below threshold at Week 2 or 6 Children with weight no greater than 30 kg receive a lower dose than children with weight greater than 30 kg or Tanner Stage IV APA 5800 The first group of 6 patients receives the initial dose of NFV If none of the 6 patients falls below the target AUC the remainder of the sample is accrued and treated at this dose If more than 1 of the 6 patients fall below the target AUC then another group of 6 patients is accrued and treated at the next higher dose If exactly 1 of the 6 patients falls below the target AUC 2 more patients are accrued and treated at the same dose If 1 of these 2 patients falls below the target AUC another group of 6 patients is tested on the next higher dose If neither of these 2 patients falls below the target AUC then the remainder of the sample is accrued and treated at this dose The dose is escalated until a dose that meets the above criteria is achieved or further dose escalation is prohibited due to toxicity The duration of therapy is 48 APA 122198104 APA 5800 208 weeks
This is a 48-week AS PER AMENDMENT APA 122198104-week APA 5800 208-week study It is designed to minimize the chance that ineffective therapy is provided short dose-escalation phase and utilizes an area under the concentration time curve AUC to establish plasma levels of DMP 266 and nelfinavir in the pediatric population that are both tolerable and efficacious APA 52698 Patients are stratified by age into Cohorts I and II and receive EFV concurrently with NFV
APA 52698 The initial starting dose of DMP 266 for patients in Cohort II is higher than the initial starting dose for patients in Cohort I APA 122198 The initial starting dose for patients in Stratum 1 of Cohort II is higher than the initial starting dose for patients in Cohort I and Stratum 2 of Cohort II The initial target AUC for DMP 266 is between 190 and 380 micromolesh uMh The initial starting dose based on a 70 kg patient and adjusted for each patients weight for the first 6 patients is adjusted on the basis of tolerability and plasma concentrations of DMP 266 after 2 weeks of daily doses If at least 4 of the first 6 patients attain a tolerable dose dose at which no more than 2 of 6 patients experience Grade 3 or worse toxicity and target AUC additional patients may continue to be accrued However if any of the initial 6 patients experience life-threatening toxicity further accrual is suspended APA 52698 An assessment of the tolerability and plasma concentrations of EFV is not required in an initial group of Cohort II patients Individual dose is based on pharmacokinetic sampling Patients receive a given starting dose of DMP 266 and continue on that dose until individual dose adjustments are needed If a patients starting dose is tolerated but the target AUC is not achieved the dose is increased If the starting dose is well tolerated and target AUC achieved no adjustment in starting dose is given to future patients If no tolerated dose achieving at least an AUC of 150 micromolesh is reached in 4 of 6 patients the study is suspended and alternative dosing regimens eg twice-daily dosing are considered
A patients current dose of DMP 266 is adjusted based on how the dose is tolerated and whether the target AUC is achieved If a patient does not achieve an AUC of greater than 110 micromolesh and experiences Grade 3 or worse toxicity the patient is discontinued from the study
APA 122198 The dose of NFV is the same for patients in Cohort I and Stratum 2 of Cohort II the dose for patients in Stratum 1 of Cohort II is higher The minimum target AUC for NFV is 10 mg x hL Doses are adjusted for an individual child if AUC falls below threshold at Week 2 or 6 Children with weight no greater than 30 kg receive a lower dose than children with weight greater than 30 kg or Tanner Stage IV APA 5800 The first group of 6 patients receives the initial dose of NFV If none of the 6 patients falls below the target AUC the remainder of the sample is accrued and treated at this dose If more than 1 of the 6 patients fall below the target AUC then another group of 6 patients is accrued and treated at the next higher dose If exactly 1 of the 6 patients falls below the target AUC 2 more patients are accrued and treated at the same dose If 1 of these 2 patients falls below the target AUC another group of 6 patients is tested on the next higher dose If neither of these 2 patients falls below the target AUC then the remainder of the sample is accrued and treated at this dose The dose is escalated until a dose that meets the above criteria is achieved or further dose escalation is prohibited due to toxicity The duration of therapy is 48 APA 122198104 APA 5800 208 weeks
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 |
|---|---|---|---|
| PACTG 382 | Registry Identifier | DAIDS ES | None |
| 10105 | REGISTRY | None | None |