Study Of An Investigational Regimen Including FDA Approved HIV Drugs In HIV-Infected Pediatric Subjects

NCT ID: NCT00071760

Last Updated: 2023-10-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 59 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2003-10-23
• Study Completion Date: 2022-03-29

Brief Summary

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.

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.

Conditions

Infection, Human Immunodeficiency Virus; HIV Infections

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm A - 4weeks - less than 2 years 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)

Group Type: EXPERIMENTAL

GW433908

Intervention Type: DRUG

Fosamprenavir suspension bid

ritonavir

Intervention Type: DRUG

Ritonavir solution bid

Arm B- 4weeks - less than 2 years 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)

Group Type: EXPERIMENTAL

GW433908

Intervention Type: DRUG

Fosamprenavir suspension bid

Interventions

GW433908

Fosamprenavir suspension bid

Intervention Type: DRUG

ritonavir

Ritonavir solution bid

Intervention Type: DRUG

Other Intervention Names

GW433908

Eligibility 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 Nucleoside Reverse Transcriptase Inhibitor (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 APV.
• Non-Nucleoside Reverse Transcriptase Inhibitor (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 Centers for Disease Control and Prevention (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).

• Minimum Eligible Age: 4 Weeks
• Maximum Eligible Age: 2 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

GlaxoSmithKline

INDUSTRY

Sponsor Role: collaborator

ViiV Healthcare

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

GSK Clinical Trials

Role: STUDY_DIRECTOR

ViiV Healthcare

Locations

GSK Investigational Site

Jacksonville, Florida, United States

GSK Investigational Site

Durham, North Carolina, United States

GSK Investigational Site

Buenos Aires, , Argentina

GSK Investigational Site

Mexico City, , Mexico

GSK Investigational Site

México, , Mexico

GSK Investigational Site

Almada, , Portugal

GSK Investigational Site

Amadora, , Portugal

GSK Investigational Site

Lisbon, , Portugal

GSK Investigational Site

San Juan, , Puerto Rico

GSK Investigational Site

Moscow, , Russia

GSK Investigational Site

Moscow, , Russia

GSK Investigational Site

Saint Petersburg, , Russia

GSK Investigational Site

Durban, KwaZulu-Natal, South Africa

GSK Investigational Site

Parow Valley, Western Province, South Africa

GSK Investigational Site

Soweto, , South Africa

Countries

United States; Argentina; Mexico; Portugal; Puerto Rico; Russia; South Africa

References

Cotton M, Cassim H, Pavia-Ruz N, Garges HP, Perger T, Ford SL, Wire MB, Givens N, Ross LL, Lou Y, Sievers J, Cheng K. Pharmacokinetics, safety and antiviral activity of fosamprenavir/ritonavir-containing regimens in HIV-infected children aged 4 weeks to 2 years-48-week study data. Pediatr Infect Dis J. 2014 Jan;33(1):57-62. doi: 10.1097/INF.0b013e3182a1123a.

Reference Type: BACKGROUND

PMID: 23811743 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

APV20002

Identifier Type: -

Identifier Source: org_study_id