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Study Of An Investigational Regimen Including FDA Approved HIV Drugs In HIV-Infected Pediatric Subjects
This study is ongoing, but not recruiting participants.

First Received on October 30, 2003.   Last Updated on January 5, 2012   History of Changes
Sponsor: ViiV Healthcare
Collaborator: GlaxoSmithKline
Information provided by: ViiV Healthcare
ClinicalTrials.gov Identifier: NCT00071760
  Purpose

This is a 48-week study to evaluate the safety, tolerability, pharmacokinetics, and antiviral activity of an investigational regimen including FDA approved HIV drugs in HIV-infected pediatric subjects, ages 4 weeks to < 2 years old.


Condition Intervention Phase
HIV Infection
Infection, Human Immunodeficiency Virus
Drug: GW433908
Drug: ritonavir
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A 48 Week, Phase II, Open-label, 2-cohort, Multicenter Study to Evaluate the Pharmacokinetics, Safety, Tolerability and Antiviral Activity of GW433908 and GW433908/RTV When Administered to HIV-1 Infected Protease Inhibitor (PI) Naive and PI-experienced Pediatric Subjects Aged 4 Weeks to <2 Years.

Resource links provided by NLM:


Further study details as provided by ViiV Healthcare:

Primary Outcome Measures:
  • Plasma APV (amprenavir) pharmacokinetic parameters following multiple dose administration of GW433908 BID or GW433908/RTV (ritonavir) BID.Incidence and nature of clinical and laboratory adverse events. [ Time Frame: 48 Weeks ] [ Designated as safety issue: No ]
  • Proportion of subjects who permanently discontinue FPV or FPV/RTV due to adverse events. [ Time Frame: 48 Weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Proportions of subjects with plasma HIV-1 RNA levels <400 copies/mL at each study visit.Change from baseline in percentage of CD4+ lymphocytes.Plasma GW433908 concentrations.Incidence of viral resistance.Subject adherence. [ Time Frame: 48 Weeks ] [ Designated as safety issue: No ]
  • Change from Baseline in the percentage of CD4+ lymphocytes at each study visit (absolute values and time-averaged)Plasma FPV concentrationsPlasma RTV AUC,ss, Cmax,ss and C,ss following multiple dose administration of FPV/RTV BID [ Time Frame: 48 Weeks ] [ Designated as safety issue: No ]
  • Relationship of steady-state plasma APV PK parameters to changes in plasma HIV-1 RNA concentrations, CD4+ percentages and/or the occurrence of adverse events [ Time Frame: 48 Weeks ] [ Designated as safety issue: No ]
  • Subject adherence and parent/guardian perceptions of study medications Incidence of viral resistance (where permissible by blood volumes) [ Time Frame: 48 Weeks ] [ Designated as safety issue: No ]

Estimated Enrollment: 48
Study Start Date: October 2003
Estimated Study Completion Date: December 2012
Estimated Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm A - 4weeks - less than 2yrs old (FPV/RTV bid)

Cohort 2A - 4weeks - less than 6 months old. Fosamprenavir (FPV) 50 mg/mL oral suspension/ritonavir (RTV) 80 mg/mL oral solution twice daily (BID)

Cohort 1A - 6 months - less than 2yrs old. Fosamprenavir (FPV) 50 mg/mL oral suspension/ritonavir (RTV) 80 mg/mL oral solution twice daily (BID)

Drug: GW433908
Fosamprenavir suspension bid
Drug: ritonavir
Ritonavir solution bid
Other Names:
  • GW433908
  • ritonavir
Experimental: Arm B- 4weeks - less than 2yrs old (FPV bid)

Cohort 2B - 4weeks - less than 6 months old. Fosamprenavir (FPV) 50 mg/mL oral suspension twice daily (BID)

Cohort 1B - 6 months - less than 2yrs old. Fosamprenavir (FPV) 50 mg/mL oral suspension twice daily (BID)

Drug: GW433908
Fosamprenavir suspension bid

Detailed Description:

A 48 week, Phase II, open-label, 2-cohort, multicenter study to evaluate the pharmacokinetics, safety, tolerability and antiviral activity of GW433908 and GW433908/RTV when administered to HIV-1 infected protease inhibitor (PI) naive and PI-experienced pediatric subjects aged 4 weeks to <2 years.

ViiV Healthcare is the new sponsor of this study, and GlaxoSmithKline is in the process of updating systems to reflect the change in sponsorship.

  Eligibility

Ages Eligible for Study:   up to 2 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male or female 4 weeks to <2 years of age. Cohort 1 (6 months - <2 years): Subjects must be <2 years of age at the Week 2 visit therefore the maximum age at screening is 22 months.

Cohort 2 (4 weeks - <6 months): Subjects must be <6 months of age at the Week 2 visit, therefore the maximum age at screening is 4 months for entry into this cohort.

  • Parent or legal guardian is willing and able to provide written informed consent for the subject to participate in the trial.
  • Screening plasma HIV-1 RNA level 400copies/mL.
  • Subjects who, in the investigator's opinion, and following viral resistance testing if conducted, are able to construct an active NRTI backbone regimen consisting of 2 NRTIs.
  • Subjects must meet one of the following criteria:

Therapy-naïve or PI-naïve subjects (defined as having received less than one week of any PI).

PI-experienced subjects defined as having prior experience with no more than three PIs. Prior RTV-boosted PI therapy will be considered as only one PI as long as the RTV dose was lower than that recommended for use of RTV as an antiretroviral agent.

Exclusion Criteria:

  • Prior history of having received AGN.
  • NNRTI therapy within 14 days prior to study drug administration (single or multiple dose) or anticipated need for concurrent NNRTI therapy during the study period.
  • PI therapy within 5 days prior to study drug administration (applicable only for subjects undergoing single dose visits)
  • Subjects and/or parents/legal guardians who, in the investigator's opinion, are not able to comply with the requirements of the study.
  • Subject is in the initial acute phase of a CDC Clinical Category C event or infection (per 1994 classification) at Baseline. Subject may be enrolled provided they are receiving treatment for the infections, such treatment not being contraindicated with FPV, and subjects are clinically improving at the Baseline visit.
  • Presence of a malabsorption syndrome or other gastrointestinal dysfunction which might interfere with drug absorption or render the subject unable to take oral medication.
  • Presence of any serious medical condition (e.g., hemoglobinopathy, chronic anemia, diabetes, cardiac dysfunction, hepatitis, or clinically relevant pancreatitis) which, in the opinion of the investigator, might compromise the safety of the subject.
  • Any acute laboratory abnormality at screen which, in the opinion of the investigator, should preclude the subject's participation in the study of an investigational compound. If subjects are found to have an acute Grade 4 laboratory abnormality at screening, this test may be repeated once within the screening window. Any verified Grade 4 laboratory abnormality would exclude a subject from study participation.
  • Grade 3 or higher (>10x ULN) serum aminotransferase levels (alanine aminotransferase, ALT and/or aspartate aminotransferase, AST) within 28 days prior to study drug administration and / or clinically relevant hepatitis within the previous 6 months.
  • Treatment with radiation therapy or cytotoxic chemotherapeutic agents within 28 days of study drug administration or an anticipated need for such treatment within the study period.
  • Treatment with immunomodulating agents (e.g., systemic corticosteroids, interleukins, interferons) or any agent with known anti-HIV activity (e.g., hydroxyurea or foscarnet) within 28 days of study drug administration.
  • Treatment with any of the following medications within 28 days prior to receiving study medication or the anticipated need during the study:

Amiodarone, astemizole, bepridil, bupropion, cisapride, clorazepate, clozapine, diazepam, dihydroergotamine, encainide, ergonovine, ergotamine, estazolam, flecainide, flurazepam, lovastatin, meperidine, methylergonovine, midazolam, pimozide, piroxicam, propafenone, propoxyphene, quinidine, simvastatin, terfenadine, and triazolam (these drugs have been excluded for safety reasons).

Carbamazepine, dexamethasone, phenobarbital, primidone, rifampin, St Johns Wort, (these drugs have been excluded because they have the potential to decrease plasma protease inhibitor concentrations).

  • Treatment with other investigational drugs/therapies within 28 days prior to receiving study medication (note: treatments available through a Treatment IND or other expanded-access mechanism will be evaluated on a case-by-case basis in consultation with the sponsor).
  • History of drug or other allergy which, in the opinion of the investigator, contraindicates participation in the trial or known hypersensitivity to any study medications (e.g. documented hypersensitivity to a nucleoside analogue).
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00071760

Locations
United States, North Carolina
GSK Investigational Site
Durham, North Carolina, United States, 27705
Argentina
GSK Investigational Site
Buenos Aires, Argentina, 1405
Mexico
GSK Investigational Site
Mexico, Mexico, 6720
GSK Investigational Site
Mexico, D.F., Mexico, 06720
Portugal
GSK Investigational Site
Almada, Portugal, 2805-267
GSK Investigational Site
Lisboa, Portugal, 1649-035
Puerto Rico
GSK Investigational Site
San Juan, Puerto Rico, 00935
Russian Federation
GSK Investigational Site
Moscow, Russian Federation, 129110
GSK Investigational Site
Moscow, Russian Federation, 105275
GSK Investigational Site
St. Petersburg, Russian Federation, 196645
South Africa
GSK Investigational Site
Parow Valley, Western Province, South Africa, 7505
GSK Investigational Site
Soweto, South Africa, 2013
Sponsors and Collaborators
ViiV Healthcare
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials ViiV Healthcare
  More Information

No publications provided

Responsible Party: Cheri Hudson; Clinical Disclosure Advisor, GSK Clinical Disclosure
ClinicalTrials.gov Identifier: NCT00071760     History of Changes
Other Study ID Numbers: APV20002
Study First Received: October 30, 2003
Last Updated: January 5, 2012
Health Authority: Spain: Spanish Agency of Medicines
United States: Food and Drug Administration

Keywords provided by ViiV Healthcare:
pediatrics
ritonavir
amprenavir
AGENERASE
HIV
Lexiva
protease inhibitors
fosamprenavir

Additional relevant MeSH terms:
Acquired Immunodeficiency Syndrome
HIV Infections
Immunologic Deficiency Syndromes
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Slow Virus Diseases
Immune System Diseases
Protease Inhibitors
Ritonavir
Fosamprenavir
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
HIV Protease Inhibitors
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on May 21, 2012