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.
A 48 Week, Phase II, Open-label, Multi-Cohort, Multicenter Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Antiviral Activity of GW433908/Ritonavir QD and GW433908/Ritonavir BID when Administered to HIV-1 Infected, Antiretroviral Naive and Experience Pediatric Subjects 2 to 18 Years Old ViiV Healthcare is the new sponsor of this study, and GlaxoSmithKline is in the process of updating systems to reflect the change in sponsorship
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
69
ritonavir oral capsules or oral solution
fosamprenavir oral suspension or tablet
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.
Time frame: 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).
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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
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GSK Investigational Site
Birmingham, Alabama, United States
GSK Investigational Site
Los Angeles, California, United States
GSK Investigational Site
Jacksonville, Florida, United States
GSK Investigational Site
Tampa, Florida, United States
GSK Investigational Site
Chicago, Illinois, United States
GSK Investigational Site
New Orleans, Louisiana, United States
GSK Investigational Site
Boston, Massachusetts, United States
GSK Investigational Site
New York, New York, United States
GSK Investigational Site
New York, New York, United States
GSK Investigational Site
Stony Brook, New York, United States
...and 32 more locations
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 0, 1, 2, 4, 8, 12, and 24 hours post dosing at Week 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)
A blood sample was drawn to determine the amount of HIV-1 RNA virus in copies per milliliter (mL) at Weeks 12, 48, 96, and 196. The percentage of participants with HIV-1 RNA \<400 copies/mL at Weeks 12, 48, 96, 168 was determined by the TLOVR algorithm with stratification by the six randomization strata. TLOVR analysis categorizes participants by treatment response. Responders were participants with confirmed viral load \<400copies/mL on two consecutive visits.
Time frame: Weeks 12, 48, 96, and 168
Median Change From Baseline HIV-1 RNA Values at Weeks 12, 48, 96, and 168 Visits
A blood sample was drawn to determine the amount of HIV-1 RNA virus in copies/mL at Weeks 12, 24, 48, 96, and 168. Change from Baseline was defined as the HIV-1 RNA level at Weeks 12, 24, 48, 96, and 168 minus the HIV-1 RNA level at Baseline.
Time frame: Baseline and Weeks 12, 48, 96, and 168
Median Change From Baseline in CD4+ Values at Week 12, 48, 96, and 168 Visits
A blood sample was drawn to determine the CD4+ cell count at Weeks 24, 48, 96, and 168. Change from Baseline was defined as the CD4+ cell count at Weeks 24, 48, 96, and 168 minus the CD4+ cell count at Baseline.
Time frame: 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
A blood sample was drawn for participants failing to respond to therapy, and the mutations present in the virus were identified. For each participant, the mutations found at the time of failure were compared with any mutations found in the blood sample at baseline. New mutations that developed at the time of virologic failure were tabulated by drug class. Virologic failure is defined as HIV-1 RNA greater than or equal to 400 copies/mL.
Time frame: Time of virologic failure