Safety, Tolerability, and Anti-HIV Activity of DMP 266 (Efavirenz) in Combination With Nelfinavir in HIV-Positive Children
NCT ID: NCT00000893
Last Updated: 2021-10-29
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.
COMPLETED
PHASE1
103 participants
INTERVENTIONAL
1997-10-31
2002-12-31
Brief Summary
Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.
Detailed Description
Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.
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.
Conditions
See the medical conditions and disease areas that this research is targeting or investigating.
Keywords
Explore important study keywords that can help with search, categorization, and topic discovery.
Study Design
Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.
TREATMENT
Interventions
Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.
Nelfinavir mesylate
Efavirenz
Eligibility Criteria
Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.
Inclusion Criteria
* Are HIV-positive.
* Are between 3 months and 16 years old (consent of parent or legal guardian required). (These age requirements reflect a change.)
* Have a plasma viral load of at least 400 copies/ml at screening.
* Agree to practice abstinence or use effective methods of birth control during the study.
* Are able to take oral medication and comply with study requirements.
* Are taking at least 1 nucleoside reverse transcriptase inhibitor (NRTI), such as zidovudine (ZDV) or stavudine (d4T). Patients can begin taking NRTIs at the beginning of the study.
Exclusion Criteria
* Have had more than 2 episodes of moderate to severe diarrhea or vomiting lasting more than 4 days within 3 months prior to study entry.
* Are allergic to EFZ or NFV.
* Have any disease, including hepatitis, cancer, or an active opportunistic (HIV-associated) infection.
* Are pregnant or breast-feeding.
* Are taking any other experimental drugs or certain medications.
* Have ever taken protease inhibitors (PIs) or nonnucleoside reverse transcriptase inhibitors (NNRTIs).
3 Months
16 Years
ALL
No
Sponsors
Meet the organizations funding or collaborating on the study and learn about their roles.
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
NIH
National Institute of Allergy and Infectious Diseases (NIAID)
NIH
Responsible Party
Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.
Principal Investigators
Learn about the lead researchers overseeing the trial and their institutional affiliations.
Courtney Fletcher
Role: STUDY_CHAIR
Stuart Starr
Role: STUDY_CHAIR
Locations
Explore where the study is taking place and check the recruitment status at each participating site.
Long Beach Memorial Med. Ctr., Miller Children's Hosp.
Long Beach, California, United States
UCLA-Los Angeles/Brazil AIDS Consortium (LABAC) CRS
Los Angeles, California, United States
Usc La Nichd Crs
Los Angeles, California, United States
Children's Hosp. & Research Ctr. Oakland, Ped. Clinical Research Ctr. & Research Lab.
Oakland, California, United States
UCSD Maternal, Child, and Adolescent HIV CRS
San Diego, California, United States
Harbor - UCLA Med. Ctr. - Dept. of Peds., Div. of Infectious Diseases
Torrance, California, United States
Howard Univ. Washington DC NICHD CRS
Washington D.C., District of Columbia, United States
Univ. of Florida Jacksonville NICHD CRS
Jacksonville, Florida, United States
Tulane/LSU Maternal/Child CRS
New Orleans, Louisiana, United States
Univ. of Maryland Med. Ctr., Div. of Ped. Immunology & Rheumatology
Baltimore, Maryland, United States
HMS - Children's Hosp. Boston, Div. of Infectious Diseases
Boston, Massachusetts, United States
WNE Maternal Pediatric Adolescent AIDS CRS
Worcester, Massachusetts, United States
Univ. of Mississippi Med. Ctr Children's Hosp.
Jackson, Mississippi, 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
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
Bronx-Lebanon Hosp. IMPAACT CRS
The Bronx, New York, United States
The Children's Hosp. of Philadelphia IMPAACT CRS
Philadelphia, Pennsylvania, United States
St. Christopher's Hosp. for Children
Philadelphia, Pennsylvania, United States
St. Jude/UTHSC CRS
Memphis, Tennessee, United States
Texas Children's Hosp. CRS
Houston, Texas, United States
Seattle Children's Hospital CRS
Seattle, Washington, United States
UW School of Medicine - CHRMC
Seattle, Washington, United States
Univ. of Puerto Rico Ped. HIV/AIDS Research Program CRS
San Juan, , Puerto Rico
San Juan City Hosp. PR NICHD CRS
San Juan, , Puerto Rico
Countries
Review the countries where the study has at least one active or historical site.
References
Explore related publications, articles, or registry entries linked to this study.
Brundage RC, Fletcher CV, Fiske WD, Kornhauser DM, McNamara J, Mofenson L, Starr SE. Pharmacokinetics of an efavirenz suspension in children. Conf Retroviruses Opportunistic Infect. 1999 Jan 31-Feb 4;6th:147 (abstract no 424)
Fletcher CV, Fenton T, Powell C, Anderson PL, Brundage RC, Spector SA, Starr SE. Pharmacologic characteristics of efavirenz (EFV) and nelfinavir (NFV) associated with virologic response in HIV-infected children. 8th Conf Retro and Opportun Infect. 2001 Feb 4-8 (abstract no 259)
Saitoh A, Hsia K, Fenton T, Powell C, Christopherson C, Fletcher CV, Starr SE, Spector SA. HIV-1 DNA persists in PBMC of children on HAART despite prolonged suppression of plasma HIV-1 RNA. 8th Conf Retro and Opportun Infect. 2001 Feb 4-8 (abstract no 685B)
Fletcher CV, Brundage RC, Fenton T, Fiske WD, Kornhauser D, McNamara J, Mofenson L, Starr SE. Efavirenz (EFV) and nelfinavir (NFV) pharmacokinetics (PK) in HIV-infected children participating in an area under the curve (AUC) controlled trial. Conf Retroviruses Opportunistic Infect. 1999 Jan 31-Feb 4;6th:136 (abstract no 366)
Starr SE, Fletcher CV, Spector SA, Yong FH, Fenton T, Brundage RC, Manion D, Ruiz N, Gersten M, Becker M, McNamara J, Mofenson LM, Purdue L, Siminski S, Graham B, Kornhauser DM, Fiske W, Vincent C, Lischner HW, Dankner WM, Flynn PM. Combination therapy with efavirenz, nelfinavir, and nucleoside reverse-transcriptase inhibitors in children infected with human immunodeficiency virus type 1. Pediatric AIDS Clinical Trials Group 382 Team. N Engl J Med. 1999 Dec 16;341(25):1874-81. doi: 10.1056/NEJM199912163412502.
Spector SA, Hsia K, Yong FH, Cabral S, Fenton T, Fletcher CV, McNamara J, Mofenson LM, Starr SE. Patterns of plasma human immunodeficiency virus type 1 RNA response to highly active antiretroviral therapy in infected children. J Infect Dis. 2000 Dec;182(6):1769-73. doi: 10.1086/317621. Epub 2000 Oct 26.
Saitoh A, Singh KK, Powell CA, Fenton T, Fletcher CV, Brundage R, Starr S, Spector SA. An MDR1-3435 variant is associated with higher plasma nelfinavir levels and more rapid virologic response in HIV-1 infected children. AIDS. 2005 Mar 4;19(4):371-80. doi: 10.1097/01.aids.0000161766.13782.2f.
Saitoh A, Fenton T, Alvero C, Fletcher CV, Spector SA. Impact of nucleoside reverse transcriptase inhibitors on mitochondria in human immunodeficiency virus type 1-infected children receiving highly active antiretroviral therapy. Antimicrob Agents Chemother. 2007 Dec;51(12):4236-42. doi: 10.1128/AAC.00893-07. Epub 2007 Sep 24.
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
10105
Identifier Type: REGISTRY
Identifier Source: secondary_id
PACTG 382
Identifier Type: -
Identifier Source: secondary_id
ACTG 382
Identifier Type: -
Identifier Source: org_study_id