48-Week Study Of GW433908 And Ritonavir Or GW433908 Alone, Twice Daily In Pediatric Patients With HIV Infection
Summary
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Plasma Amprenavir (APV) AUC (0-tau[τ]) |
22.3; NA; 24.1; NA; NA; 55.3 | — |
| PRIMARY Plasma APV Cmax |
7.15; NA; 6.52; NA; NA; 8.66 | — |
| PRIMARY Plasma APV Cτ |
0.55; NA; 0.70; NA; NA; 3.39 | — |
| PRIMARY Plasma APV CL/F Following Dosing Expressed in mg/kg |
19.3; NA; 23.4; NA; NA; 6.06 | — |
| PRIMARY Plasma APV CL/F Following Dosing Expressed in mg |
269; NA; 330; NA; NA; 91 | — |
| PRIMARY Plasma APV Tmax |
1.17; NA; 1.00; NA; NA; 1.25 | — |
| PRIMARY Plasma APV t1/2 |
3.03; NA; 3.18; NA; NA; 5.21 | — |
| PRIMARY Number of Participants Who Permanently Discontinued the Treatment Due to Any Adverse Event (AE) |
0; 4 | — |
| PRIMARY Change From Baseline in Triglycerides, Total Cholesterol, Low-density Lipoprotein (LDL) Cholesterol, High-density Lipoprotein (HDL) Cholesterol, and Serum Glucose at Week 48 |
0.1; 0.2; 1.1; 0.9; 0.4; 0.3 | — |
| PRIMARY Change From Baseline in Serum Lipase at Week 48 |
-2.0; -1.0 | — |
| PRIMARY Change From Baseline in Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) at Week 48 |
-3; -7; -6; -9 | — |
| PRIMARY Number of Participants With Treatment-emergent (TE) Grade 3/4 Clinical Chemistry Laboratory Abnormalities |
2; 2; 2; 2; 0; 2 | — |
| SECONDARY Plasma Ritonavir (RTV) AUC (0-τ) |
3.98; 7.13; 6.46; 5.74; 6.13 | — |
| SECONDARY Plasma RTV Cmax |
0.633; 1.100; 0.980; 0.750; 1.06 | — |
| SECONDARY Plasma RTV Cτ |
0.224; 0.297; 0.228; 0.263; 0.220 | — |
| SECONDARY Plasma RTV CL/F Following Dosing Expressed in mg/kg |
12.9; 6.81; 5.94; 8.61; 5.59 | — |
| SECONDARY Plasma RTV CL/F Following Dosing Expressed in mg |
195; 190; 258; 279; 272 | — |
| SECONDARY Plasma RTV Tmax |
3.92; 4.00; 4.01; 5.92; 3.96 | — |
| SECONDARY Plasma RTV t1/2 |
3.43; 3.39; 3.97; 2.84; 3.64 | — |
| SECONDARY Plasma FPV AUC (0-τ) |
— | — |
| SECONDARY Plasma FPV Cmax and Cτ |
— | — |
| SECONDARY Plasma FPV CL/F Following Dosing Expressed in mg/kg |
— | — |
| SECONDARY Plasma FPV CL/F Following Dosing Expressed in mg |
— | — |
| SECONDARY Plasma FPV Tmax |
— | — |
| SECONDARY Plasma FPV t1/2 |
— | — |
| SECONDARY Number of Participants (Par.) With Virological Outcome (Plasma HIV-1 Ribonucleic Acid [RNA] <400 Copies/mL) at Week 48 |
12; 36; NA; 19; 4; 3 | — |
| SECONDARY Number of Participants (Par.) With Plasma HIV-1 Ribonucleic Acid (RNA) <400 Copies Per Milliliter at Baseline and Weeks 2,12, 24, and 48 (MSD=F) |
0; 0; NA; 0; 3; 9 | — |
| SECONDARY Median Plasma HIV-1 RNA (log10 Copies/mL) at Baseline and Weeks 2, 12, 24, and 48 (Observed Analysis) |
5.13; 4.72; NA; 4.53; 3.27; 3.06 | — |
| SECONDARY Median Change From Plasma HIV-1 RNA (log10 Copies/mL) at Weeks 2, 12, 24, and 48 (Observed Analysis) |
-1.91; -1.84; NA; -1.58; -3.04; -2.77 | — |
| SECONDARY Number of Participants With at Least a 1.0 log10 HIV-1 RNA Decrease From Baseline at Weeks 2, 12, 24, and 48 (Observed Analysis) |
13; 35; NA; 22; 19; 41 | — |
| SECONDARY Cluster of Differentiation Antigen 4 (CD4+) Cell Count at Baseline and at Weeks 2, 12, 24, and 48 |
810; 370; 820; 450; 1040; 581 | — |
| SECONDARY Change From Baseline in CD4+ Cell Count at Weeks 2, 12, 24, and 48 |
20; 60; 170; 180; 350; 184 | — |
| SECONDARY Percentage of Total Lymphocytes (TLs) That Are CD4+ Cells at Baseline and Weeks 2, 12, 24, and 48 |
19; 21; 24; 23; 27; 25 | — |
| SECONDARY Change From Baseline in the Percentage of Total Lymphocytes (TLs) That Are CD4+ Cells at Weeks 2, 12, 24, and 48 |
3; 1; 6; 5; 7; 8 | — |
| SECONDARY Number of Confirmed Virologic Failure Participants (Par.) With Treatment-emergent HIV Genotypic Resistance in Reverse Transcriptase and Protease |
3; 0; 0; 1; 3; 0 | — |
| SECONDARY Number of Confirmed Virologic Failure Participants (Par.) Since the Week 48 Analysis With Treatment-emergent HIV Genotypic Resistance in Reverse Transcriptase and Protease |
1; 1; 2; 0; 0; 1 | — |
| SECONDARY Number of Confirmed Virologic Failure Participants (Par.) With Treatment-emergent Reductions in Drug Susceptibility (DS) |
3; 0; 0; 2; 1; 0 | — |
| SECONDARY Number of Confirmed Virologic Failure Participants (Par.) Since the Week 48 Analysis With Treatment-emergent Reductions in Drug Susceptibility (DS) |
1; 1; 3; 0; 0; 1 | — |
| SECONDARY Number of Participants Reporting Perfect Adherence Over the 3 Days Prior to the Study Visits at Weeks 2, 12, 24, and 48 as Assessed by Study Coordinator Using the Pediatric AIDS Clinical Trials Group (PACTG) Adherence Questionnaire |
15; 49; 15; 15; NA; 22 | — |
| SECONDARY Correlation Between Plasma APV Exposure and Plasma vRNA, CD4+ Cell Counts, and the Occurrence of Adverse Events |
— | — |
Eligibility Criteria
Inclusion criteria
- Males or females 2 to 18 years of age Cohorts 1A and 1B, up to one month before 6th birthday at Baseline/Day 1 Cohort 2, up to one month before 12th birthday at Baseline/Day 1 Cohort 3, up to one month before 19th birthday at Baseline/Day 1
- A female is eligible to enter and participate in this study if she is of:
- non-childbearing potential (i.e., physiologically incapable of becoming pregnant, including any female who is pre-menarchial); or,
- 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). Premenarchial females who develop child-bearing potential while on the study will be expected to follow one of the methods of contraception listed below.
Agreement for 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 counseled and be willing to use one of the contraception 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.
Hormonal contraception is not recommended, due to decreased efficacy of contraception as well as increased risk of hepatic transaminase elevation (see Section 8.2).
All subjects of childbearing potential or developing child-bearing potential while participating in this study should be counseled 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 >=400copies/mL.
- Subjects must meet one of the following criterion:
Antiretroviral therapy (ART)-naïve or PI-naïve subjects (defined as having received less than one week of any PI and any length of therapy with Nucleoside Reverse Transcriptase Inhibitors (NRTIs) and/or Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs)).
PI-experienced subjects (defined as having received greater than one week prior PI therapy 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 age
Exclusion criteria
- Prior history of having received APV or FPV for >7 days.
- NNRTI use within 14 days prior to study drug administration or anticipated need for concurrent NNRTI therapy during the treatment period of the study.
- Subjects 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 infection, such treatment not being contraindicated with FPV, and the 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.
- Pregnant or lactating females.
- Presence of any serious medical condition (e.g., hemoglobinopathy, chronic anemia, a history of insulin resistance, diabet
Data sourced from ClinicalTrials.gov (NCT00089583). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.