Trial to Evaluate Steady State Pharmacokinetic Parameters, Efficacy and Safety of Nevirapine in Antiretroviral Drug naïve Pediatric Patients

This study has been completed.
Sponsor:
Information provided by:
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
NCT00273975
First received: January 9, 2006
Last updated: October 30, 2013
Last verified: October 2013
  Purpose

Trial to evaluate steady state pharmacokinetic parameters of nevirapine 150mg/m2 and nevirapine 4 or 7 mg/kg after 4 weeks, and efficacy and safety of the dosing when administered for 48 weeks in antiretroviral drug naïve paediatric patients.


Condition Intervention Phase
HIV Infections
Drug: Nevirapine
Drug: Lamivudine
Drug: Zidovudine
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Randomised Open Label Multi-centre Trial to Evaluate the Pharmacokinetic, Efficacy and Safety Parameters of Nevirapine 150mg/m2 and Nevirapine 4 or 7 mg/kg When Administered in Combination With AZT and 3TC for 48 Weeks in Antiretroviral naïve Paediatric Patients.

Resource links provided by NLM:


Further study details as provided by Boehringer Ingelheim:

Primary Outcome Measures:
  • Area under the concentration-time curve over one dosing interval (AUCτ) [ Time Frame: 1, 3 and 6 hours on Day 28 ] [ Designated as safety issue: No ]
  • Maximum observed concentration (Cmax) [ Time Frame: 1, 3 and 6 hours on Day 28 ] [ Designated as safety issue: No ]
  • Minimum observed concentration (Cmin) [ Time Frame: 1, 3 and 6 hours on Day 28 ] [ Designated as safety issue: No ]
  • Oral clearance (Dose/AUC) at steady state [ Time Frame: 1, 3 and 6 hours on Day 28 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Change in HIV-1 RNA count [ Time Frame: week 2, 4, 8, 12, 18, 24, 30, 36, 42,48 ] [ Designated as safety issue: No ]
  • Virologic Response [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
  • Time to Virologic Suppression [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
  • Virologic Failure [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
  • Time to Virologic Failure [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
  • Treatment Failure [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
  • Time to Treatment Failure [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
  • Change in CD4+ cell count [ Time Frame: week 2, 4, 8, 12, 18, 24, 30, 36, 42,48 ] [ Designated as safety issue: No ]
  • Change in CD4+ percent [ Time Frame: week 2, 4, 8, 12, 18, 24, 30, 36, 42,48 ] [ Designated as safety issue: No ]
  • Occurrence of Adverse Events [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
  • Occurrence of Rash [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]

Estimated Enrollment: 123
Study Start Date: January 2002
Estimated Study Completion Date: December 2004
Primary Completion Date: December 2004 (Final data collection date for primary outcome measure)
Detailed Description:

A randomised open label multi-centre trial to evaluate the pharmacokinetic, efficacy and safety parameters of nevirapine 150mg/m2 and nevirapine 4 or 7mg/kg when administered in combination with ZDV and 3TC for 48 weeks in antiretroviral naive pediatric patients.

Primary objective: To evaluate steady state pharmacokinetic parameters of nevirapine 150mg/m2 in antiretroviral drug naive pediatric patients.

Secondary objective: To assess efficacy and safety of nevirapine 150 mg/m2 and nevirapine 4/7mg/kg after 24 and 48 weeks of treatment

Study Hypothesis:

Evaluation of recent pharmacokinetic data has suggested that a dose based on body surface area rather than body weight might be a better therapeutic regimen to achieve steady state plasma concentrations. The goal in this study was to determine if a Nevirapine suspension dose of 150 mg/m2 BID, following a two week lead-in of 150 mg/m2 QD, produces plasma nevirapine steady state concentrations of 4 - 6 ?g/mL in all age groups as was observed in adult safety and efficacy trials.

Comparison(s):

ACTG 245

  Eligibility

Ages Eligible for Study:   3 Months to 16 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion:

  1. Male or female patients between 3 months and 16 years of age at day 28 of the study.
  2. Evidence of HIV-1 infection
  3. Patients who are antiretroviral drug naive
  4. Plasma viral load detectable
  5. CD4 >=50 cells/cc3
  6. Written informed permission
  7. Active assent given by the patient if the child is capable of understanding the given information
  8. Reasonable probability for completion of the trial

Exclusion:

  1. Any significant disease, other than HIV
  2. Any acute illness within 2 weeks prior to Day 0
  3. Patients requiring the continued use of inhibitors or inducers of P450 metabolic enzymes
  4. Patients requiring systematic treatment with CYP3A4 substrates
  5. Patients with malabsorption, severe chronic diarrhea
  6. Receipt of any cytotoxic therapy for malignancy
  7. Current grade 3 or 4 clinical or laboratory toxicity
  8. Pregnancy or breast-feeding
  9. Females of childbearing potential not using adequate contraception. allergy or known drug hypersensitivity to any of the study drugs intravenous drug abuse, alcohol or substance abuse
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00273975

Locations
South Africa
Groote Schuur Hospital
Cape Town, South Africa, 7900
Boehringer Ingelheim Investigational Site
Pretoria, South Africa
Boehringer Ingelheim Investigational Site
Soweto, South Africa, 2013
Boehringer Ingelheim Investigational Site
Tygerberg, South Africa, 7505
Sponsors and Collaborators
Boehringer Ingelheim
Investigators
Study Chair: Boehringer Ingelheim Study Coordinator B.I. South Africa (Pty.) Ltd.
  More Information

Additional Information:
No publications provided

ClinicalTrials.gov Identifier: NCT00273975     History of Changes
Other Study ID Numbers: 1100.1368
Study First Received: January 9, 2006
Last Updated: October 30, 2013
Health Authority: South Africa: Medicines Control Council

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Zidovudine
Nevirapine
Lamivudine
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Anti-HIV Agents

ClinicalTrials.gov processed this record on August 27, 2014