Safety, Tolerability, and Anti-HIV Activity of DMP 266 (Efavirenz) in Combination With Nelfinavir in HIV-Positive Children
- Conditions
- HIV Infections
- Registration Number
- NCT00000893
- 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 \[AS PER AMENDMENT (APA) 12/21/98:104-week\] \[APA 5/8/00: 208-week\] 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. \[APA 5/26/98: Patients are stratified by age into Cohorts I and II\] and receive EFV concurrently with NFV.
\[APA 5/26/98: The initial starting dose of DMP 266 for patients in Cohort II is higher than the initial starting dose for patients in Cohort I.\] \[APA 12/21/98: The initial starting dose for patients in Stratum 1 of Cohort II is higher than the initial starting dose for patients in Cohort I and Stratum 2 of Cohort II.\] The initial target AUC for DMP 266 is between 190 and 380 micromoles/h (uM/h). The initial starting dose (based on a 70 kg patient and adjusted for each patient's 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. \[APA 5/26/98: An assessment of the tolerability and plasma concentrations of EFV is not required in an initial group of Cohort II patients. Individual dose is based on pharmacokinetic sampling.\] Patients receive a given starting dose of DMP 266 and continue on that dose until individual dose adjustments are needed. If a patient's 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 micromoles/h is reached in 4 of 6 patients, the study is suspended and alternative dosing regimens, e.g., twice-daily dosing, are considered.
A patient's 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 micromoles/h and experiences Grade 3 or worse toxicity, the patient is discontinued from the study.
\[APA 12/21/98: The dose of NFV is the same for patients in Cohort I and Stratum 2 of Cohort II; the dose for patients in Stratum 1 of Cohort II is higher.\] The minimum target AUC for NFV is 10 mg x h/L. 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. \[APA 5/8/00: The first group of 6 patients receives the initial dose of NFV. If none of the 6 patients falls below the target AUC, the remainder of the sample is accrued and treated at this dose. If more than 1 of the 6 patients fall below the target AUC, then another group of 6 patients is accrued and treated at the next higher dose. If exactly 1 of the 6 patients falls below the target AUC, 2 more patients are accrued and treated at the same dose. If 1 of these 2 patients falls below the target AUC, another group of 6 patients is tested on the next higher dose. If neither of these 2 patients falls below the target AUC, then the remainder of the sample is accrued and treated at this dose. The dose is escalated until a dose that meets the above criteria is achieved or further dose escalation is prohibited due to toxicity.\] The duration of therapy is 48 \[APA 12/21/98:104\] \[APA 5/8/00: 208\] weeks.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 103
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (27)
The Children's Hosp. of Philadelphia IMPAACT CRS
🇺🇸Philadelphia, Pennsylvania, United States
UCLA-Los Angeles/Brazil AIDS Consortium (LABAC) CRS
🇺🇸Los Angeles, California, United States
Bronx-Lebanon Hosp. IMPAACT CRS
🇺🇸Bronx, New York, United States
St. Christopher's Hosp. for Children
🇺🇸Philadelphia, Pennsylvania, United States
Usc La Nichd Crs
🇺🇸Los Angeles, California, United States
Long Beach Memorial Med. Ctr., Miller Children's Hosp.
🇺🇸Long Beach, California, United States
Univ. of Puerto Rico Ped. HIV/AIDS Research Program CRS
🇵🇷San Juan, Puerto Rico
Children's Hosp. & Research Ctr. Oakland, Ped. Clinical Research Ctr. & Research Lab.
🇺🇸Oakland, California, United States
Seattle Children's Hospital CRS
🇺🇸Seattle, Washington, United States
UW School of Medicine - CHRMC
🇺🇸Seattle, Washington, United States
Harlem Hosp. Ctr. NY NICHD CRS
🇺🇸New York, New York, United States
NYU Med. Ctr., Dept. of Medicine
🇺🇸New York, New York, United States
Nyu Ny Nichd Crs
🇺🇸New York, New York, United States
Texas Children's Hosp. CRS
🇺🇸Houston, Texas, United States
HMS - Children's Hosp. Boston, Div. of Infectious Diseases
🇺🇸Boston, Massachusetts, United States
St. Jude/UTHSC CRS
🇺🇸Memphis, Tennessee, United States
Univ. of Mississippi Med. Ctr Children's Hosp.
🇺🇸Jackson, Mississippi, United States
San Juan City Hosp. PR NICHD CRS
🇵🇷San Juan, Puerto Rico
Howard Univ. Washington DC NICHD CRS
🇺🇸Washington, District of Columbia, United States
Univ. of Maryland Med. Ctr., Div. of Ped. Immunology & Rheumatology
🇺🇸Baltimore, Maryland, United States
Univ. of Florida Jacksonville NICHD CRS
🇺🇸Jacksonville, Florida, United States
WNE Maternal Pediatric Adolescent AIDS CRS
🇺🇸Worcester, Massachusetts, United States
Tulane/LSU Maternal/Child CRS
🇺🇸New Orleans, Louisiana, United States
Harbor - UCLA Med. Ctr. - Dept. of Peds., Div. of Infectious Diseases
🇺🇸Torrance, California, United States
UCSD Maternal, Child, and Adolescent HIV CRS
🇺🇸San Diego, California, United States
SUNY Downstate Med. Ctr., Children's Hosp. at Downstate NICHD CRS
🇺🇸Brooklyn, New York, United States
Metropolitan Hosp. Ctr.
🇺🇸New York, New York, United States