A Clinical Study Of An Investigational Regimen Including Marketed HIV Drugs In HIV-1 Pediatric Subjects Ages 2-18 Years

NCT00040664 | Completed Phase 2 Results

• 1 other identifier: APV 20003
• Study Type: interventional
• Target: 69
• Locations: 7 countries
• Sites: 42

Brief Summary

This is a 48-week study to collect additional information on the safety, tolerability, pharmacokinetics, and antiviral activity of an investigational regimen (course of therapy) including FDA approved HIV drugs in HIV-infected patients 2 - 18 years old.

Conditions

HIV Infection

Keywords

pediatrics; HIV; protease inhibitors; ritonavir; fosamprenavir; LEXIVA; AGENERASE; amprenavir

Outcome Measures

Primary Outcomes (11)

• Number of Participants Who Discontinued Treatment Due to Adverse Events

  The number of participants who prematurely discontinued study drug due to adverse events was tabulated. Data are summarized by individual adverse event.

  Baseline through end of study (at least Week 168)

• Number of Participants With Any Drug-related Grade 2 to 4 Adverse Event

  The number of participants with drug-related adverse events coded as Grade 2 (mild), Grade 3 (severe), or Grade 4 (life-threatening).

  Baseline through end of study (at least Week 168)

• Number of Participants With Grade 3 or 4 Treatment-emergent Laboratory Abnormalities

  The number of participants with Grade 3 (severe) or Grade 4 (life-threatening) laboratory abnormalities while on study treatment.

  Baseline through end of study (at least Week 168)

• Geometric Mean of Steady State Plasma Amprenavir (APV) Parameter: AUC(0-tau)

  Geometric mean is a type of "average" that indicates the central tendency of a set of values and is calculated by multiplying all the numbers in a set, and then taking the nth root of the resulting product. AUC(0-tau)=area under the concentration curve from time 0 to tau.

  0, 1, 2, 4, 8, 12, and 24 hours post dosing at Week 4

• Geometric Mean of Steady State Plasma APV Parameter: Cmax

  Geometric mean is a type of "average" that indicates the central tendency of a set of values and is calculated by multiplying all the numbers in a set, and then taking the nth root of the resulting product. Cmax= concentration maximum.

  0, 1, 2, 4, 8, 12, and 24 hours post dosing at Week 4

• Median Steady State Plasma APV Tmax

  tmax: time after administration of the drug when maximum concentration is reached

  0, 1, 2, 4, 8, 12, and 24 hours post dosing at Week 4

• Geometric Mean of Steady State Plasma APV Parameter: CL/F

  Geometric mean is a type of "average" that indicates the central tendency of a set of values and is calculated by multiplying all the numbers in a set, and then taking the nth root of the resulting product. CL/F=apparent plasma clearance.

  0, 1, 2, 4, 8, 12, and 24 hours post dosing at Week 4

• Geometric Mean of Steady State Plasma APV Parameter: t1/2

  Geometric mean is a type of "average" that indicates the central tendency of a set of values and is calculated by multiplying all the numbers in a set, and then taking the nth root of the resulting product. t1/2=elimination half-life. t1/2=elimination half-life.

  0, 1, 2, 4, 8, 12, and 24 hours post dosing at Week 4

• Least Squares Mean of Plasma APV Parameter: AUC0-tau

  A blood sample was drawn on Week 4 over 24 hours (at 0, 1, 2, 4, 8, 12, and 24 hours post dosing). Ratio of geometric least squares mean (90% CI) are presented. Ctau=trough concentration. PK Parameters for QD and BID are compared with Historical adult data. Least squares mean (LSM) are the group means after having controlled for a covariate (i.e., holding it constant at some typical value of the covariate, such as its mean value). LSM is calculated by taking the average of the means within a treatment.

  0, 1, 2, 4, 8, 12, and 24 hours post dosing at Week 4

• Least Squares Mean of Plasma APV Parameter: Cmax

  A blood sample was drawn on Week 4 over 24 hours (at 0, 1, 2, 4, 8, 12, and 24 hours post dosing). Ratio of geometric least squares mean (90% CI) are presented. Ctau=trough concentration. PK Parameters for QD and BID are compared with Historical adult data. Least squares mean (LSM) are the group means after having controlled for a covariate (i.e., holding it constant at some typical value of the covariate, such as its mean value). LSM is calculated by taking the average of the means within a treatment.

  0, 1, 2, 4, 8, 12, and 24 hours post dosing at Week 4.

• Least Squares Mean of Plasma APV Parameter: Ctau

  A blood sample was drawn on Week 4 over 24 hours (at 0, 1, 2, 4, 8, 12, and 24 hours post dosing). Ratio of geometric least squares mean (90% CI) are presented. Ctau=trough concentration. PK Parameters for QD and BID are compared with Historical adult data. Least squares mean (LSM) are the group means after having controlled for a covariate (i.e., holding it constant at some typical value of the covariate, such as its mean value). LSM is calculated by taking the average of the means within a treatment.

  0, 1, 2, 4, 8, 12, and 24 hours post dosing at Week 4.

Secondary Outcomes (4)

• Percentage of Participants With HIV-1 RNA <400 Copies Per mL at Weeks 12, 48, 96, and 168 (Time to Loss of Virologic Response [TLOVR] Analysis)

  Weeks 12, 48, 96, and 168

• Median Change From Baseline HIV-1 RNA Values at Weeks 12, 48, 96, and 168 Visits

  Baseline and Weeks 12, 48, 96, and 168

• Median Change From Baseline in CD4+ Values at Week 12, 48, 96, and 168 Visits

  Baseline and Weeks 12, 48, 96, and 168

• Number of Participants With APV Resistance Associated HIV-1 RNA Genotypic Mutations and Phenotypic Resistance at Time of Virologic Failure Not Present at Baseline

  Time of virologic failure

Study Arms (3)

2 to 5 years (FPV/RTV)

EXPERIMENTAL

Two to five years. Fosamprenavir (FPV) 700 mg tablets or 50 mg/mL oral suspension/ritonavir (RTV) 100 mg capsules or 80 mg/mL oral solution once daily (QD)

Drug: ritonavir; Drug: fosamprenavir

6 to 11 years (FPV/RTV)

EXPERIMENTAL

Six to twelve years. Fosamprenavir (FPV) 700 mg tablets or 50 mg/mL oral suspension/ritonavir (RTV) 100 mg capsules or 80 mg/mL oral solution once daily (QD)

Drug: ritonavir; Drug: fosamprenavir

12 to 18 years (FPV/RTV)

EXPERIMENTAL

Twelve to Eighteen years. Fosamprenavir (FPV) 700 mg tablets or 50 mg/mL oral suspension/ritonavir (RTV) 100 mg capsules or 80 mg/mL oral solution once daily (QD)

Drug: ritonavir; Drug: fosamprenavir

Interventions

ritonavir DRUG

ritonavir oral capsules or oral solution

Also known as: fosamprenavir

12 to 18 years (FPV/RTV); 2 to 5 years (FPV/RTV); 6 to 11 years (FPV/RTV)

fosamprenavir DRUG

fosamprenavir oral suspension or tablet

12 to 18 years (FPV/RTV); 2 to 5 years (FPV/RTV); 6 to 11 years (FPV/RTV)

Eligibility Criteria

• Age: 2 Years - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Male or females 2 to 18 years of age
• A female is eligible to enter and participate in this study if she is of:
• a. non-childbearing potential (i.e., physiologically incapable of becoming pregnant, including any female who is pre-menarchial); or,
• b. child-bearing potential with a negative serum pregnancy test at screen, a negative urine pregnancy test on Day 1 and who agrees to use one of the following methods of contraception (any contraception method must be used consistently and correctly, i.e., in accordance with both the product label and the instructions of a physician). Note: hormonal contraceptives are not considered a sufficient form of contraceptive for this study.
• Complete abstinence from intercourse from 2 weeks prior to administration of study drugs, throughout the study and for 2 weeks after discontinuation of all study medications. Should a female subject of childbearing potential decide to become sexually active during the course of the study, she must be counselled and be willing to use one of the methods listed below:
• Double barrier contraception (male condom/spermicide, male condom/diaphragm, diaphragm/spermicide)
• Any intrauterine device (IUD) with published data showing that the expected failure rate is less than 1% per year (not all IUDs meet this criterion)
• Any other method with published data showing that the lowest expected failure rate for that method is less than 1% per year. All subjects participating in this study should be counselled on the practice of safe/safer sex.
• Parent or legal guardian (and subject whenever possible) has the ability to understand and provide written informed consent for the subject to participate in the trial. Verbal witnessed assent must be obtained from the subject whenever possible.
• Screening plasma HIV-1 RNA \> or =400copies/mL.
• Subject's who, in the investigator's opinion, and following resistance testing where appropriate, are able to construct an active NRTI backbone regimen consisting of 2 NRTIs.
• Subjects must meet one of the following criteria:
• ART-naïve subjects are defined as having had \< 4 weeks (28 days) therapy with an NRTI, no previous therapy with an NNRTI and \< 1 week therapy with an HIV PI.
• ART-experienced subjects are defined as having had greater than 4 weeks (28 days) therapy with any NRTI(s) and any length of therapy with any NNRTI(s) and/or a PI. PI-experienced subjects will be eligible if they have previously been treated with \< three PIs, excluding AGENERASE. Prior therapy with a RTV boosted PI regimen will be considered as only 1 prior PI as long as the RTV dose was below that recommended for use of RTV as an antiretroviral agent. This specific criterion is not applicable to subjects in screening and/or enrolling after approval of Amendment No. 4. - For subjects screening and/or enrolling after the approval of Amendment No.4, PI naive subjects are defined as ART experienced subjects having less than one week of therapy with a PI and no prior experience with AGENERASE. Prior treatment with NNRTIs and NRTIs is permitted (however, subjects will NOT be permitted to receive concurrent NNRTI therapy while participating in this study)

You may not qualify if:

• Prior history of having received amprenavir.
• Use of non-nucleoside reverse transcriptase inhibitor (NNRTI) therapy within 14 days of study Day 1 or anticipated need for concurrent NNRTI therapy during the study period.
• Have had an AIDS defining illness (acute CDC Category C event) within 28 days of screening.
• Pregnant or lactating.
• Non-nucleoside reverse transcriptase inhibitor therapy within 14 days prior to study drug administration or anticipated need for concurrent NNRTI therapy during the study period.
• Subjects who, in the investigator's opinion, are not able to comply with the requirements of the study.
• An acute CDC Category C event (per 1993/1994 classification) and/or serious bacterial infection(s) within 28 days prior to study drug administration.
• 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 and hepatitis) which, in the opinion of the investigator, might compromise the safety of the subject.
• Current grade 2 or higher serum lipase within 28 days prior to study drug administration and/or history of clinically relevant pancreatitis within the previous 6 months. - Grade 3 or 4 transaminase levels (ALT and/or 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, diazepin, dihydroergotamine, encainide, ergonovine, ergotamine, estazolam, flecainide, flurazepam, lovastatin, meperidine, methylergonovine, midazolam, pimozide, piroxicam, propafenone, propoxyphene, quinidine, rifabutin, simvastatin, terfenadine, triazolam, zolpidem (these drugs have been excluded for safety reasons).
• Carbamazepine, dexamethasone, phenobarbital, phenytoin, primidone, rifampin, St Johns Wort (these drugs have been excluded because they have the potential to decrease plasma protease inhibitor concentrations) - Systemic chemotherapeutic agents

Sponsors & Collaborators

• ViiV Healthcare: lead

Study Sites (42)

GSK Investigational Site

Birmingham, Alabama, 35233, United States

Location

GSK Investigational Site

Los Angeles, California, 90027, United States

Location

GSK Investigational Site

Jacksonville, Florida, 32209, United States

Location

GSK Investigational Site

Tampa, Florida, 33613, United States

Location

GSK Investigational Site

Chicago, Illinois, 60614, United States

Location

GSK Investigational Site

New Orleans, Louisiana, 70112, United States

Location

GSK Investigational Site

Boston, Massachusetts, 02118, United States

Location

GSK Investigational Site

New York, New York, 10016, United States

Location

GSK Investigational Site

New York, New York, 10021, United States

Location

GSK Investigational Site

Stony Brook, New York, 11794-8111, United States

Location

GSK Investigational Site

The Bronx, New York, 10457, United States

Location

GSK Investigational Site

Chapel Hill, North Carolina, 27599-7220, United States

Location

GSK Investigational Site

Durham, North Carolina, 27705, United States

Location

GSK Investigational Site

Cleveland, Ohio, 44106, United States

Location

GSK Investigational Site

Dallas, Texas, 75235, United States

Location

GSK Investigational Site

Fort Worth, Texas, 76104, United States

Location

GSK Investigational Site

Richmond, Virginia, 23298, United States

Location

GSK Investigational Site

Toronto, Ontario, M5G 1X8, Canada

Location

GSK Investigational Site

Montreal, Quebec, H3T 1C5, Canada

Location

GSK Investigational Site

Modena, Emilia-Romagna, 41150, Italy

Location

GSK Investigational Site

Rome, Lazio, 00165, Italy

Location

GSK Investigational Site

Genoa, Liguria, 16132, Italy

Location

GSK Investigational Site

Milan, Lombardy, 20122, Italy

Location

GSK Investigational Site

Milan, Lombardy, 20142, Italy

Location

GSK Investigational Site

Pavia, Lombardy, 27100, Italy

Location

GSK Investigational Site

Florence, Tuscany, 55100, Italy

Location

GSK Investigational Site

Padua, Veneto, 35128, Italy

Location

GSK Investigational Site

Rotterdam, 3015 GE, Netherlands

Location

GSK Investigational Site

Amadora, 2700, Portugal

Location

GSK Investigational Site

Lisbon, 1150, Portugal

Location

GSK Investigational Site

Lisbon, 1649-035, Portugal

Location

GSK Investigational Site

Bucharest, 021105, Romania

Location

GSK Investigational Site

Bucharest, 030303, Romania

Location

GSK Investigational Site

Barcelona, 08003, Spain

Location

GSK Investigational Site

Barcelona, 08035, Spain

Location

GSK Investigational Site

Barcelona, 08950, Spain

Location

GSK Investigational Site

Madrid, 28007, Spain

Location

GSK Investigational Site

Madrid, 28041, Spain

Location

GSK Investigational Site

Madrid, 28047, Spain

Location

GSK Investigational Site

Palma de Mallorca, 07014, Spain

Location

GSK Investigational Site

Seville, 41013, Spain

Location

GSK Investigational Site

Valencia, 46009, Spain

Location

MeSH Terms

Conditions

HIV Infections

Interventions

Ritonavir; fosamprenavir

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 5, 2002
• First Posted: July 10, 2002
• Study Start: July 1, 2002
• Primary Completion: October 1, 2008
• Study Completion: October 1, 2008
• Last Updated: March 3, 2017
• Results First Posted: February 23, 2010

Record last verified: 2017-01

Locations

IT (8); PT (3); RO (2); ES (9); US (17); CA (2); NL (1)