A Study to Evaluate the Pharmacokinetics, Safety, Tolerability, and Antiviral Efficacy of TMC278 in Human Immunodeficiency Virus Infected Adolescents

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Janssen R&D Ireland
ClinicalTrials.gov Identifier:
NCT00799864
First received: November 26, 2008
Last updated: October 1, 2014
Last verified: October 2014
  Purpose

The purpose of this study is to evaluate the pharmacokinetics (what the body does to the drug), safety and effectiveness of TMC278 25 mg once daily in combination with an investigator-selected background regimen containing 2 nucleoside reverse transcriptase inhibitors (NRTIs) (zidovudine [AZT]/lamivudine [3TC] or abacavir [ABC]/3TC) in antiretroviral (ARV) treatment.


Condition Intervention Phase
Human Immuno Deficiency (HIV) Infections
Drug: TMC278
Drug: Zidovudine
Drug: Abacavir
Drug: Tenofovir disoproxil fumarate
Drug: Lamivudine
Drug: Emtricitabine
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II, Open Label, Single Arm Trial to Evaluate the Pharmacokinetics,Safety, Tolerability, and Antiviral Activity of TMC278 in Antiretroviral Naive HIV-1 Infected Adolescents Aged 12 to < 18 Years

Resource links provided by NLM:


Further study details as provided by Janssen R&D Ireland:

Primary Outcome Measures:
  • Pharmacokinetics of TMC278 as measured by maximum plasma concentration (Cmax) [ Time Frame: Up to 48 weeks ] [ Designated as safety issue: No ]
  • Pharmacokinetics of TMC278 as measured by area under the plasma concentration curve (AUC24) [ Time Frame: Up to 48 weeks ] [ Designated as safety issue: No ]
    AUC24 is defined area under the plasma concentration time curve from 0 to 24 hours post dosing of TMC278.

  • Pharmacokinetics of TMC278 as measured by time to reach the maximum plasma concentration (tmax) [ Time Frame: Up to 48 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Number of patients with adverse events (part 1 and part 2) [ Time Frame: Up to 244 weeks (including 4 week follow up visit) ] [ Designated as safety issue: No ]
    Safety measures include adverse events, vital signs, physical examination, hematology, biochemistry and electrocardiogram

  • Change in CD4+ cells and viral load (part 2) [ Time Frame: Screening (2 months prior to treatment) to Week 240 ] [ Designated as safety issue: No ]
    Change in the CD4+ cells will evaluate immunologic changes at week 24 and 48 weeks of treatment with TMC278

  • Evolution of viral genotype and phenotype (part 2) [ Time Frame: Up to post Week 48 extension (Week 240) ] [ Designated as safety issue: No ]
    This endpoint is measured at 24 and 48 weeks of treatment with TMC278.

  • Treatment adherence as measured by the Study Adherence Questionnaire (part 2) [ Time Frame: Up to 48 weeks ] [ Designated as safety issue: No ]
    This endpoint is measured by Study Adherence Questionnaire for children and teenagers. The adherence questionnaire should be completed by by the patient. Ths questionnaire includes questions about the medicine, it's color and dosage.

  • Assessment of pharmacokinetic-pharmacodynamic relationships [ Time Frame: Up to 48 weeks ] [ Designated as safety issue: No ]
    This endpoint evaluates pharmacokinetic-pharmacodynamic relationships for safety and efficacy of TMC278


Enrollment: 38
Study Start Date: January 2011
Estimated Study Completion Date: October 2018
Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: TMC278
The patients will receive TMC278 along with 2 nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) as a back ground regimen. The NRTIs includes zidovudine, abacavir, or tenofovir disoproxil fumarate in combination with lamivudine or emtricitabine
Drug: TMC278
Type=exact, form=tablet, unit=mg, number=25, route=oral. The patients will receive TMC278 once daily for 48 weeks.
Drug: Zidovudine
Type=exact, form=tablet, unit=mg, route=oral. The patients will receive this selected NRTI once daily for 48 weeks.
Drug: Abacavir
Type=exact, form=tablet, unit=mg, route=oral. The patients will receive this selected NRTI once daily for 48 weeks.
Drug: Tenofovir disoproxil fumarate
Type=exact, form=tablet, unit=mg, route=oral. The patients will receive this selected NRTI once daily for 48 weeks.
Drug: Lamivudine
Type=exact, form=tablet, unit=mg, route=oral. The patients will receive this selected NRTI once daily for 48 weeks.
Drug: Emtricitabine
Type=exact, form=tablet, unit=mg, route=oral. The patients will receive this selected NRTI once daily for 48 weeks.

Detailed Description:

This is a 48-week, Phase II, open-label (all people involved know the identity of the assigned drug) and single arm study. The study will consist of a screening period of maximum 6 weeks, a treatment period of maximum 48 weeks, and a 4 week follow-up period taking place regardless of the presence of serious adverse events (SAEs) if patients withdraw early (ie, before Week 48) or if patients do not participate in the extension after Week 48; also after Week 48, a 4-week follow-up visit is only required in case of ongoing SAEs at the final on treatment visit. The initial 48-week treatment period will be structured into 2 parts. The first part includes part 1a and part 1b. The first part of the trial is designed to evaluate the steady-state pharmacokinetic (PK) profile and the short-term safety and antiviral activity of TMC278 25 mg once daily when administered in combination with 2 NRTIs, in adolescents. At Week 2/4, intensive PK will be done and an analysis together with short-term safety and antiviral activity will be reviewed by a data monitoring committee (DMC). If the mean steady-state exposure in this first group of patients is comparable to that of the adult population (ie, is within 80-125 percentage of the mean exposure of the 25 mg once daily dose group in study, TMC278-C204), and the Week 2 safety and antiviral activity results have been reviewed and deemed satisfactory by the DMC, the second part of the trial will start. Week 12 interim analysis will be performed when all Part 1a and Part 1b patients have reached 12 weeks of treatment or discontinued earlier. If the mean exposure in adolescents is greater than 125 percentage of the mean exposure in adults, but antiviral activity results are satisfactory and there are no safety concerns, as judged by the DMC, the second part of the trial will start. If the mean exposure in adolescents is greater than 125 percentage of the mean exposure in adults, the antiviral activity is satisfactory, but there are safety concerns that potentially could be avoided by a lower exposure to TMC278, as judged by the IDMC, patients up to a certain body weight (determined based on the intensive PKresults) will be switched to a lower, weight adjusted dose of TMC278. However, if the mean exposure in adolescents is less than 80 percentage of the mean exposure in adults or the Week 2 results are not deemed satisfactory, all patients will be seen for a withdrawal visit, treatment with TMC278 will be stopped, patients will be switched to a locally available ARV regimen, and the trial will be stopped. The second part of the trial will evaluate long-term (48 weeks) safety, efficacy, and pharmacokinetics of TMC278 in combination with the background regimen of 2 NRTIs with a primary analysis time point at 24 weeks. In both parts of the trial, the ART will consist of TMC278 25 mg once daily and an investigator-selected background regimen containing 2 NRTIs. Patients safety will be monitored through out the study and during the follow up visits.

  Eligibility

Ages Eligible for Study:   12 Years to 18 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Has diagnosed with documented chronic human immuno deficiency virus (HIV-1) infection who is aware of his/her HIV-1 diagnosis
  • Must have weight greater than or equal to 32 kg
  • Must have HIV-1 plasma viral load at screening greater than equal to 5,000 HIV-1 ribonucleic acid (RNA) copies/mL
  • Have not received treatment with a therapeutic HIV vaccine or an HIV drug with the exception of a single dose of nevirapine (NVP) prior to screening
  • In the judgment of the investigator, it is appropriate to initiate anti retroviral therapy (ARV) therapy based on the patients medical condition and taking into account guidelines for the treatment of HIV-1 infection in children of this age group.

Exclusion Criteria:

  • Any previous use of ARVs with the exception of single dose NVP
  • Plasma viral load at screening greater than 100,000 HIV-1 ribonucleic acid (RNA) copies/mL
  • Documented genotypic evidence of non-nucleoside reverse transcriptase inhibitor (NNRTI) resistance at screening or from historical data available in the source documents
  • Use of disallowed concomitant therapy from 4 weeks prior to the baseline visit
  • Patient has any currently active Acquired Immunodeficiency Syndrome (AIDS) defining illness
  • Patient has active tuberculosis and/or is being treated for tuberculosis at screening
  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: NCT00799864

Locations
United States, New York
Syracuse, New York, United States
United States, Tennessee
Memphis, Tennessee, United States
India
Chennai, India
Mangalore, India
South Africa
Bloemfontein, South Africa
Dundee, South Africa
Port Elizabeth, South Africa
Pretoria, South Africa
Thailand
Bangkok, Thailand
Khon Kaen, Thailand
Uganda
Kampala, Uganda
Ukraine
Kiev, Ukraine
Sponsors and Collaborators
Janssen R&D Ireland
Investigators
Study Director: Janssen R&D Ireland Clinical Trial Janssen R&D Ireland
  More Information

No publications provided

Responsible Party: Janssen R&D Ireland
ClinicalTrials.gov Identifier: NCT00799864     History of Changes
Other Study ID Numbers: CR002677, TMC278-TiDP38-C213, 2008-001696-30
Study First Received: November 26, 2008
Last Updated: October 1, 2014
Health Authority: Europe: European Medicines Agency
United States: Food and Drug Administration
Ukraine: State Pharmacological Center - Ministry of Health

Keywords provided by Janssen R&D Ireland:
HIV Infections
Antiretroviral
HIV-1
AIDS
TMC278

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

ClinicalTrials.gov processed this record on October 29, 2014