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Safety and Effectiveness of Emtricitabine, Efavirenz, and Didanosine in HIV Infected Children Who Have Taken Few or No Anti-HIV Drugs

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT00016718
First Posted: August 31, 2001
Last Update Posted: October 17, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborator:
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
  Purpose
Treatment of HIV-infected patients involves combining drugs from different classes of anti-HIV drugs. One preferred regimen for adults is 2 nucleoside reverse transcriptase inhibitors (NRTIs) and 1 protease inhibitor (PI). For children, this regimen may be too complicated or the drugs may be too difficult to take by mouth. The purpose of this study was to determine the long-term safety and effectiveness of daily didanosine (ddI), efavirenz (EFV), and emtricitabine (FTC) in pediatric patients who had taken few or no anti-HIV drugs.

Condition Intervention Phase
HIV Infections Drug: Didanosine (ddI) Drug: Efavirenz (EFV) Drug: Emtricitabine (FTC) Phase 1 Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Masking Description:
open-label
Primary Purpose: Treatment
Official Title: An Open-Label Study to Evaluate the Safety, Tolerance, Antiviral Activity, and Pharmacokinetics of Emtricitabine in Combination With Efavirenz and Didanosine in a Once-Daily Regimen in HIV Infected, Antiretroviral Therapy Naive or Very Limited Antiretroviral Exposed Pediatric Subjects

Resource links provided by NLM:


Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Primary Outcome Measures:
  • Proportion of Participants Who Developed Grade 3 or 4 Adverse Events Attributed to the Study Treatment. [ Time Frame: At study entry, weeks 2 and 4, every 4 weeks up to week 96 and every 6 weeks thereafter for Group 1 participants and at study entry, weeks 2 and 4, every 4 weeks up to week 144 and every 12 weeks thereafter for Groups 2 and 3 ]

    Adverse events were graded using the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Version 1.0, December 2004, Clarification August 2009, which is available on the RCC website at (http://rcc.tech-res.com/). Adverse Events of Grade 3 or 4 laboratory abnormalities or signs and symptoms that were judged by the study team to be possibly or probably related to the study treatment.

    Comparisons between age groups were not required as per protocol.


  • Proportion of Participants With Suppression of HIV Viral Load to Less Than 400 Copies/ml at Week 16 [ Time Frame: At week 16 ]
    Proportion was calculated as number of participants with HIV-1 RNA <= 400 copies/ml relative to the number of participants with HIV-1 RNA measured at that time point.

  • Proportion of Participants With Suppression of HIV Viral Load to Less Than 50 Copies/ml at Week 16 [ Time Frame: At week 16 ]
    Proportion was calculated as number of participants with HIV-1 RNA <= 50 copies/ml relative to the number of participants with HIV-1 RNA measured at that time point.


Enrollment: 43
Study Start Date: August 2001
Study Completion Date: January 2009
Primary Completion Date: January 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Age Group 1: 90 days to < 3 years of age (FTC, EFV, ddI)
Emtricitabine (FTC), Efavirenz (EFV) and Didanosine (ddI) together once daily
Drug: Didanosine (ddI)
Antiretroviral Didanosine (ddI) : 240 mg/m^2 up to a maximum of 400 mg once daily
Other Name: Videx, Videx EC
Drug: Efavirenz (EFV)
Antiretroviral For Age Group 1 Efavirenz (EFV): dose adjusted for body size and for Age Groups 2 and 3 Efavirenz (EFV): up to a maximum of 600 mg once daily as a capsule ot 720 mg as an oral solution
Other Name: Sustiva
Drug: Emtricitabine (FTC)
Antiretroviral Emtricitabine (FTC): 6 mg/Kg up to a maximum of 200 mg once daily
Other Name: Emtriva
Experimental: Age Group 2: 3 to 12 years of age (FTC, EFV, ddI)
Emtricitabine (FTC), Efavirenz (EFV) and Didanosine (ddI) together once daily
Drug: Didanosine (ddI)
Antiretroviral Didanosine (ddI) : 240 mg/m^2 up to a maximum of 400 mg once daily
Other Name: Videx, Videx EC
Drug: Efavirenz (EFV)
Antiretroviral For Age Group 1 Efavirenz (EFV): dose adjusted for body size and for Age Groups 2 and 3 Efavirenz (EFV): up to a maximum of 600 mg once daily as a capsule ot 720 mg as an oral solution
Other Name: Sustiva
Drug: Emtricitabine (FTC)
Antiretroviral Emtricitabine (FTC): 6 mg/Kg up to a maximum of 200 mg once daily
Other Name: Emtriva
Experimental: Age Group 2: 13 to 21 years of age (FTC, EFV, ddI)
Emtricitabine (FTC), Efavirenz (EFV) and Didanosine (ddI) together once daily
Drug: Didanosine (ddI)
Antiretroviral Didanosine (ddI) : 240 mg/m^2 up to a maximum of 400 mg once daily
Other Name: Videx, Videx EC
Drug: Efavirenz (EFV)
Antiretroviral For Age Group 1 Efavirenz (EFV): dose adjusted for body size and for Age Groups 2 and 3 Efavirenz (EFV): up to a maximum of 600 mg once daily as a capsule ot 720 mg as an oral solution
Other Name: Sustiva
Drug: Emtricitabine (FTC)
Antiretroviral Emtricitabine (FTC): 6 mg/Kg up to a maximum of 200 mg once daily
Other Name: Emtriva

Detailed Description:

Anti-HIV treatment options are limited for pediatric patients because combination therapies recommended for adults may not be appropriate for children or adolescents. Few PIs are available in formulations appropriate for pediatric patients, and complex dosing schedules and food requirements may be detrimental to treatment adherence. A once-daily regimen of the NRTIs ddI and FTC and the nonnucleoside reverse transcriptase inhibitor (NNRTI) EFV has been shown safe and well tolerated in adults.

This Phase I/II open label study evaluated the long-term safety and efficacy of a ddI, FTC, and EFV regimen in pediatric patients. All study patients were either absolutely naive to antiretroviral therapy or had received less than or equal to 56 days perinatal prophylaxis or less than 7 days of cumulative antiretroviral therapy prior to study entry, and had a plasma screening plasma HIV-1 RNA levels >= 5000 copies/mL. This study was written to characterize the disposition of FTC, determine the PK data for ddI-EC QD, comparing the bio-availability of the enteric coated formulation with ddI pediatric powder for oral solution, and to provide insight into the age related pharmacokinetics differences observed in this and other studies.

HIV infected pediatric patients were stratified into three age Groups: Group 1: 90 days to <3 years of age; Group 2: 3 years to 12 years of age (inclusive); and Group 3: 13 to 21 years of age (inclusive). The initial study doses for the triple drug regimen was FTC, 6 mk/kg up to a maximum of 200 mg once daily, for EFV, the dose for age Group 1 was determined in PACTG 382 and dose adjusted for body size, and the doses for age Groups 2 and 3 were defined in the dosing table of the protocol of up to a maximum of 600 mg once daily as a capsule or 720 mg as an oral solution; for ddI, 240 mg/m2 up to a maximum of 400 mg once daily. Comparison of age groups was not required as per the protocol.

Patients were followed for a maximum of 192 weeks; all patients were to receive ddI, EFV, and FTC together once daily. Study visits occurred at study entry, Weeks 2,and 4, and every 4 weeks thereafter. Blood collection, medical history assessment, and a physical exam occurred at all visits; urine collection occurred at selected visits. Intensive pharmacokinetic (PK) studies was done at Weeks 2 and 12 to determine if dose adjustments were required for any of the drugs. If virologic failure was determined, PK studies was repeated 4 weeks after adjustments in therapy. Parents or guardians were asked to complete treatment adherence questionnaires at some visits. Some patients were also asked to participate in an additional PK study after Week 16 or week 96.

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   90 Days to 21 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • HIV infected
  • Antiretroviral naive OR have received no more than 56 days of drugs to prevent mother-to-child transmission of HIV OR have received less than 7 total days of antiretroviral therapy
  • Viral load of 5,000 copies/ml or more
  • Any Center for Disease Control (CDC) classification and immune status
  • Able to swallow study medications
  • Parent or guardian willing to provide informed consent, if applicable
  • Willing to use acceptable forms of contraception
  • female subjects of childbearing potential with a negative serum beta human chronic gonadotropin

Exclusion Criteria:

  • Allergic to study medications or their formulations
  • Kidney disease
  • Positive for hepatitis B or C
  • Acute opportunistic infection (OI) or bacterial infection requiring treatment at study entry
  • Taking drugs to treat tuberculosis
  • Taking anti-HIV drugs other than those included in this study
  • Hemoglobin >= grade 3 at screening
  • Absolute Neutrophil counts >= grade 2 at screening
  • Platelets >= Grade 2 at screening
  • Bilirubin >= Grade 2 at screening
  • SGOT (AST), SGPT(ALT) >= Grade 2 at screening
  • Non-fasting triglycerides >= Grade 2 at screening. Confirmed by a 2nd determination >=100 mg/dl at fasting state
  • Pancreatic amylase or total amylase+ lipase >= Grade 2 at screening
  • Taking any investigational drugs
  • Anti-cancer drugs within 1 year of study screening
  • Serious medical event within 21 days of study screening
  • Active or history of pancreatitis
  • Require certain medications. Patients requiring short courses of steroids (less than 14 days) for asthma are not excluded.
  • Active or history of significant peripheral neuropathy
  • Difficulty with food or severe chronic diarrhea within 30 days before study entry
  • Unable to eat at least 1 meal per day (or to feed at least 3 times per day, for infants) because of chronic nausea, vomiting, swallowing problems, or stomach upset
  • Unable to swallow oral medications
  • Pregnant or breastfeeding
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00016718


Locations
United States, California
UCSD Maternal, Child, and Adolescent HIV CRS
San Diego, California, United States
UCSF Pediatric AIDS CRS
San Francisco, California, United States, 941430105
United States, Colorado
Univ. of Colorado Denver NICHD CRS
Aurora, Colorado, United States, 802181088
United States, District of Columbia
Howard Univ. Washington DC NICHD CRS
Washington, D.C., District of Columbia, United States, 20060
United States, Florida
Univ. of Florida Jacksonville NICHD CRS
Jacksonville, Florida, United States, 32209
Univ. of Miami Ped. Perinatal HIV/AIDS CRS
Miami, Florida, United States, 33161
United States, Illinois
Chicago Children's CRS
Chicago, Illinois, United States, 606143394
Rush Univ. Cook County Hosp. Chicago NICHD CRS
Chicago, Illinois, United States
United States, Massachusetts
Children's Hosp. of Boston NICHD CRS
Boston, Massachusetts, United States, 021155724
WNE Maternal Pediatric Adolescent AIDS CRS
Worcester, Massachusetts, United States, 016550001
United States, New York
Nyu Ny Nichd Crs
New York, New York, United States, 10016
Harlem Hosp. Ctr. NY NICHD CRS
New York, New York, United States
SUNY Upstate Med. Univ., Dept. of Peds.
Syracuse, New York, United States, 13210
United States, North Carolina
DUMC Ped. CRS
Durham, North Carolina, United States, 277103499
United States, Tennessee
St. Jude/UTHSC CRS
Memphis, Tennessee, United States, 381052794
United States, Texas
Texas Children's Hosp. CRS
Houston, Texas, United States, 77030
Puerto Rico
Univ. of Puerto Rico Ped. HIV/AIDS Research Program CRS
San Juan, Puerto Rico, 009365067
San Juan City Hosp. PR NICHD CRS
San Juan, Puerto Rico, 009367344
Sponsors and Collaborators
National Institute of Allergy and Infectious Diseases (NIAID)
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Investigators
Study Chair: Ross E. McKinney, Jr., MD Duke University
Study Chair: Mobeen H. Rathore, MD Pediatric Infectious Diseases/Immunology, University of Florida Health Science Center
  More Information

Additional Information:
Publications:
Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00016718     History of Changes
Other Study ID Numbers: P1021
10038 ( Registry Identifier: DAIDS ES )
ACTG P1021
PACTG P1021
IMPAACT P1021
First Submitted: May 31, 2001
First Posted: August 31, 2001
Results First Submitted: August 1, 2017
Results First Posted: October 17, 2017
Last Update Posted: October 17, 2017
Last Verified: September 2017

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Didanosine
Drug Therapy, Combination
Drug Administration Schedule
Reverse Transcriptase Inhibitors
Anti-HIV Agents
Pharmacokinetics
Deoxycytidine
Efavirenz
Treatment Naive

Additional relevant MeSH terms:
HIV Infections
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Emtricitabine
Efavirenz
Didanosine
Antiviral Agents
Anti-Infective Agents
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Retroviral Agents
Anti-HIV Agents
Cytochrome P-450 CYP2C9 Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Cytochrome P-450 CYP2C19 Inhibitors
Cytochrome P-450 CYP2B6 Inducers
Cytochrome P-450 Enzyme Inducers
Cytochrome P-450 CYP3A Inducers
Antimetabolites