Infection, Human Immunodeficiency Virus I, HIV-1 Infection
Conditions
Keywords
protease inhibitor,, HIV-1,, Fosamprenavir,, non-HDL cholesterol, ritonavir,, naive,
Brief summary
This is a Phase IIIB, 48 Week, multicentre, randomized, open-label, parallel group study comparing the safety and efficacy of fosamprenavir plus ritonavir 1400mg/100mg once-daily to fosamprenavir plus ritonavir 700mg/100mg twice-daily, both administered with abacavir/lamivudine 600mg/300mg once-daily in antiretroviral-naive HIV-1 infected adults. This study utilizes a group-sequential design with two stages: 1) an interim 24 week cohort analysis of approximately 200 subjects and 2) if study continuation criteria are met at this interim analysis, further enrolment of an additional 528 subjects, followed over a minimum of 48 weeks. The objectives of the study are to demonstrate 1) non-inferior antiviral activity of fosamprenavir/ritonavir 1400mg/100mg QD compared to fosamprenavir/ritonavir 700mg/100mg BID and 2) a superior fasting non-HDL lipid profile in subjects receiving fosamprenavir/ritonavir 1400mg/100mg QD.
Interventions
Fosamprenavir (FPV, TELZIR) is currently licensed in Europe for twice daily (BID) dosing in combination with ritonavir (RTV, Norvir) as a boosting agent
Sponsors
GlaxoSmithKline
ViiV Healthcare
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Subject is ≥18 years of age. * Subject is antiretroviral-naïve (defined as having ≤14 days of prior therapy with any antiretroviral agent). * Subject has plasma HIV-1 RNA ≥1,000 copies/mL at screening. * Subject is willing and able to understand and provide written informed consent prior to participation in this study. * A female is eligible to enter and participate in the study if she is of: 1. Non-childbearing potential (i.e., physiologically incapable of becoming pregnant, including any female who is post-menopausal); or, 2. Child-bearing potential, has a negative pregnancy test (serum b-HCG) at screen and agrees to one of the following methods of contraception (any contraception method must be used consistently and correctly, i.e., in accordance with both the approved product label and the instructions of a physician): * Complete abstinence from intercourse from 2 weeks prior to administration of the investigational products, throughout the study, and for at least 2 weeks after discontinuation of all study medications * Double barrier method (male condom/spermicide, male condom/diaphragm, diaphragm/spermicide). Hormonal contraception will not be permitted in this study * Any intrauterine device (IUD) with published data showing that the expected failure rate is \<1% per year. * Sterilization (female subject or male partner of female subject). All subjects participating in the study should be counselled on the practice of safer sex. * Prior to randomization, subjects entering Stage 2 must have been screened and be negative for the HLA-B\*5701 allele. Test may be performed by local laboratory and results must be available for source document verification according to local practices.
Exclusion criteria
* Subject is in the initial acute phase of a CDC Clinical Category C infection at Baseline. Subjects may be enrolled provided they are receiving treatment for such infections and are clinically improving at the Baseline visit. * Subject is enrolled in one or more investigational drug protocols, which may impact HIV RNA suppression. * Subject is, in the opinion of the Investigator, unable to complete the study dosing period and protocol evaluations and assessments. * Subject is either pregnant or breastfeeding. * Subject suffers from any serious medical condition (such as pancreatitis, diabetes, congestive heart failure, cardiomyopathy or other cardiac dysfunction) which in the opinion of the Investigator would compromise the safety of the subject. * Subject has a pre-existing mental, physical, or substance abuse disorder which, in the opinion of the Investigator, may interfere with the subject's ability to comply with the dosing schedule and protocol evaluations and assessments. * Subject has a history of inflammatory bowel disease or intestinal malignancy, intestinal ischemia, malabsorption, or other gastrointestinal dysfunction, which, in the opinion of the Investigator, may interfere with drug absorption or render the subject unable to take oral medication. * Subject has any acute laboratory abnormality at screening, which, in the opinion of the Investigator, would 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 45-day screening window. Any verified Grade 4 laboratory abnormality would exclude a subject from study participation. * Subject has an estimated creatinine clearance \< 50 mL/min via the Cockcroft-Gault method \[Cockcroft, 1976\]. This test may be repeated once within the 45-day screening window. NOTE: Creatinine clearance should be estimated using the following formula: For serum creatinine concentration in mg/dL: For serum creatinine concentration in µmol/L: * Alanine aminotransferase (ALT) \>5 times the upper limit of normal (ULN) or hepatic impairment as determined by Child-Pugh Score ≥ 5. * Subject is receiving, or has received within 90 days prior to screen, any lipid lowering agent, including drugs from the following classes: HMG-CoA reductase inhibitors (statins), niacin, fibrates, bile acid sequestrants, and/or fish oil supplements. Subjects anticipated to require initiation of therapy with these agents within 12 weeks of Baseline are not eligible to participate. * Subject has received treatment with radiation therapy or cytotoxic chemotherapeutic agents within 28 days prior to Screening, or has an anticipated need for these agents within the study period. * Subject has received treatment with an HIV-1 immunotherapeutic vaccine or any agents with documented activity against HIV-1 in vitro within 28 days prior Screening, or an anticipated need during the study. * Subjects who require treatment with any of the following medications within 28 days of commencement of investigational product, or an anticipated need during the study: * Amiodarone, astemizole, bepridil, cisapride, dihydroergotamine, ergonovine, ergotamine, flecainide, halofantrine, lidocaine, lovastatin, methylergonovine, midazolam, pimozide, propafenone, quinidine, simvastatin, terfenadine, triazolam. * Carbamazepine, dexamethasone, phenobarbital, phenytoin, primidone, rifampin, St Johns Wort (Hypericum perforatum), troglitazone. * Systemic interleukins or interferons. * Subject has a history of allergy to any of the investigational products or any excipients therein. * Subject has evidence of genotypic (as defined by the current ANRS AC-11 algorithm) resistance at screening or prior documented evidence of genotypic and/or phenotypic (above threshold for reduced susceptibility) resistance to amprenavir/ritonavir, abacavir or lamivudine. * Subjects recruited at sites in France will be excluded if: * The subject is not affiliated with or a beneficiary of a social security. * The subject has previously participated in an experimental drug and/or vaccine trial(s) within 60 days or 5 half-lives, or twice the duration of the biological effect of the experimental drug or vaccine - whichever is longer, prior to screening for the study. * The subject will participate simultaneously in another clinical study. Notwithstanding these minimum inclusion and
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With HIV-1 RNA <400 and >=400 Copies/mL Over 48 Weeks | Week 48 | A blood sample was drawn to determine the amount of HIV-1 RNA virus in copies/mL at week 48. The percentage of participants with HIV-1 RNA \<400 copies/mL at Week 48 was determined by the Time to Loss Of Virologic Response (TLOVR) algorithm. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With HIV-1 RNA <400 Copies/mL (Primary Endpoint) at Week 48 Categorised by Baseline Viral Load, TLOVR Analysis | Week 48 | The number of participants with HIV-1 RNA \<400 copies/mL at Week 48 was determined (by analysis of blood draw) and categorised by baseline viral load (BVL). |
| Number of Participants With HIV-1 RNA <400 Copies/mL (Primary Endpoint) at Week 48 Categorised by Baseline CD4+ Count, TLOVR Analysis | Week 48 | The number of participants with HIV-1 RNA \<400 copies/mL at week 48 was determined (by analysis of blood draw) and categorised by baseline CD4+ count. |
| Change From Baseline in Non-HDL Cholesterol at Week 48 | Week 48 | Blood samples were drawn to determine the non-HDL cholesterol levels at Week 48. The mean absolute change in non-HDL cholesterol was defined as the Week 48 levels minus levels at baseline. |
| Percentage of Participants With HIV-1 RNA <50 and >=50 Copies/mL by Visit Over 48 Weeks | Week 48 | A blood sample was drawn to determine the amount of HIV-1 RNA virus in copies/mL at week 48. The percentage of participants with HIV-1 RNA \<50 copies/mL at Week 48 was determined by the TLOVR algorithm |
| Steady-state Levels of Amprenavir (APV) and Ritonavir (RTV) Ctau at Weeks 4, 12, and 24 | Weeks 4, 12, and 24 | Blood samples were drawn at Weeks 4, 12, and 24 to determine plasma concentrations (Ctau) of APV and RTV |
| Study Endpoints for a Subset of Subjects Receiving Study Drug Beyond 48 Weeks | Up to 60 weeks | Adaptive two-stage design study up to 48 weeks. N=200, expanding to 728 if continuation criteria were achieved based on a 24-week interim analysis. The initial 200 participants would continue until the last subject of the expanded cohort reached 48 weeks and would constitute the subset. As continuation criteria were not achieved, the study did not proceed to the second stage, and full analysis was performed on the initial 200 participants only. |
| Number of Protocol-defined Virological Failures With Genotypic and Phenotypic Resistance Changes | Time to virologic failure; Week 4 up to Week 48 | A blood sample was drawn at the time of confirmation of virological failure, and mutations present in the virus were identified and compared to those found in the blood sample at baseline. New mutations were tabulated by drug class. RT, reverse transcriptase. Virological failure could occur anytime from Week 4 to Week 48. |
Countries
Belgium, France, Germany, Italy, Romania, Russia, Spain, Switzerland, United Kingdom
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| FPV/RTV 1400/100 mg Once Daily (QD) + ABC/3TC FDC 600/300 mg Q Fosamprenavir (FPV)/ritonavir (RTV) 1400 mg/100 mg once daily administered with abacavir/lamivudine fixed dose combination (ABC/3TC FDC) 600/300 mg once daily | 106 |
| FPV/RTV 700/100 mg BID + ABC/3TC FDC 600/300 mg QD FPV/RTV 700 mg/100 mg twice daily administered with ABC/3TC FDC 600/300 mg once daily | 106 |
| Total | 212 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 5 | 7 |
| Overall Study | Could not comply with scheduled visits | 1 | 0 |
| Overall Study | Lost to Follow-up | 4 | 5 |
| Overall Study | Patient could not swallow Norvir | 1 | 0 |
| Overall Study | Patient went to Brazil | 1 | 0 |
| Overall Study | Protocol-defined virologic failure | 1 | 0 |
| Overall Study | Protocol Violation | 1 | 1 |
| Overall Study | Withdrawal by Subject | 2 | 2 |
| Overall Study | Withdrawal due to pregnancy | 0 | 1 |
Baseline characteristics
| Characteristic | FPV/RTV 700/100 mg BID + ABC/3TC FDC 600/300 mg QD | Total | FPV/RTV 1400/100 mg Once Daily (QD) + ABC/3TC FDC 600/300 mg Q |
|---|---|---|---|
| Age, Customized | 38 years | 38 years | 37 years |
| Race/Ethnicity, Customized African American/African heritage | 22 participants | 45 participants | 23 participants |
| Race/Ethnicity, Customized American Indian/Alaskan native | 3 participants | 6 participants | 3 participants |
| Race/Ethnicity, Customized Asian - South East Asian | 2 participants | 4 participants | 2 participants |
| Race/Ethnicity, Customized Mixed race | 0 participants | 2 participants | 2 participants |
| Race/Ethnicity, Customized White - Arabic/North African | 1 participants | 2 participants | 1 participants |
| Race/Ethnicity, Customized White - White/Caucasian/European | 78 participants | 153 participants | 75 participants |
| Sex: Female, Male Female | 29 Participants | 56 Participants | 27 Participants |
| Sex: Female, Male Male | 77 Participants | 156 Participants | 79 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 79 / — | 72 / — |
| serious Total, serious adverse events | 19 / — | 18 / — |
Outcome results
Primary
Percentage of Participants With HIV-1 RNA <400 and >=400 Copies/mL Over 48 Weeks
A blood sample was drawn to determine the amount of HIV-1 RNA virus in copies/mL at week 48. The percentage of participants with HIV-1 RNA \<400 copies/mL at Week 48 was determined by the Time to Loss Of Virologic Response (TLOVR) algorithm.
Time frame: Week 48
Population: Intent-to-Treat-Exposed (ITT-E) Population: All randomised participants who received at least one dose of study medication
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| FPV/RTV 1400/100 mg Once Daily (QD) + ABC/3TC FDC 600/300 mg Q | Percentage of Participants With HIV-1 RNA <400 and >=400 Copies/mL Over 48 Weeks | HIV-1 RNA <400 copies/mL | 81 Percentage of participants |
| FPV/RTV 1400/100 mg Once Daily (QD) + ABC/3TC FDC 600/300 mg Q | Percentage of Participants With HIV-1 RNA <400 and >=400 Copies/mL Over 48 Weeks | HIV-1 RNA >=400 copies/mL | 19 Percentage of participants |
| FPV/RTV 700/100 mg BID + ABC/3TC FDC 600/300 mg QD | Percentage of Participants With HIV-1 RNA <400 and >=400 Copies/mL Over 48 Weeks | HIV-1 RNA <400 copies/mL | 82 Percentage of participants |
| FPV/RTV 700/100 mg BID + ABC/3TC FDC 600/300 mg QD | Percentage of Participants With HIV-1 RNA <400 and >=400 Copies/mL Over 48 Weeks | HIV-1 RNA >=400 copies/mL | 18 Percentage of participants |
95% CI: [-11.4, 9.5]
Secondary
Change From Baseline in Non-HDL Cholesterol at Week 48
Blood samples were drawn to determine the non-HDL cholesterol levels at Week 48. The mean absolute change in non-HDL cholesterol was defined as the Week 48 levels minus levels at baseline.
Time frame: Week 48
Population: Safety Population: all participants who received at least one dose of study medication
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| FPV/RTV 1400/100 mg Once Daily (QD) + ABC/3TC FDC 600/300 mg Q | Change From Baseline in Non-HDL Cholesterol at Week 48 | 1.10 mmol/L (millimoles/Liter) | Standard Deviation 0.81 |
| FPV/RTV 700/100 mg BID + ABC/3TC FDC 600/300 mg QD | Change From Baseline in Non-HDL Cholesterol at Week 48 | 1.26 mmol/L (millimoles/Liter) | Standard Deviation 0.9 |
Secondary
Number of Participants With HIV-1 RNA <400 Copies/mL (Primary Endpoint) at Week 48 Categorised by Baseline CD4+ Count, TLOVR Analysis
The number of participants with HIV-1 RNA \<400 copies/mL at week 48 was determined (by analysis of blood draw) and categorised by baseline CD4+ count.
Time frame: Week 48
Population: ITT-E Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| FPV/RTV 1400/100 mg Once Daily (QD) + ABC/3TC FDC 600/300 mg Q | Number of Participants With HIV-1 RNA <400 Copies/mL (Primary Endpoint) at Week 48 Categorised by Baseline CD4+ Count, TLOVR Analysis | <150 cells/mm3 (n=24, 23) | 18 Participants |
| FPV/RTV 1400/100 mg Once Daily (QD) + ABC/3TC FDC 600/300 mg Q | Number of Participants With HIV-1 RNA <400 Copies/mL (Primary Endpoint) at Week 48 Categorised by Baseline CD4+ Count, TLOVR Analysis | >=150 to <250 cells/mm3 (n=29, 31) | 24 Participants |
| FPV/RTV 1400/100 mg Once Daily (QD) + ABC/3TC FDC 600/300 mg Q | Number of Participants With HIV-1 RNA <400 Copies/mL (Primary Endpoint) at Week 48 Categorised by Baseline CD4+ Count, TLOVR Analysis | >=250 to <350 cell/mm3 (n=29, 31) | 23 Participants |
| FPV/RTV 1400/100 mg Once Daily (QD) + ABC/3TC FDC 600/300 mg Q | Number of Participants With HIV-1 RNA <400 Copies/mL (Primary Endpoint) at Week 48 Categorised by Baseline CD4+ Count, TLOVR Analysis | >=350 cell/mm3 (n=24, 21) | 21 Participants |
| FPV/RTV 700/100 mg BID + ABC/3TC FDC 600/300 mg QD | Number of Participants With HIV-1 RNA <400 Copies/mL (Primary Endpoint) at Week 48 Categorised by Baseline CD4+ Count, TLOVR Analysis | >=350 cell/mm3 (n=24, 21) | 19 Participants |
| FPV/RTV 700/100 mg BID + ABC/3TC FDC 600/300 mg QD | Number of Participants With HIV-1 RNA <400 Copies/mL (Primary Endpoint) at Week 48 Categorised by Baseline CD4+ Count, TLOVR Analysis | <150 cells/mm3 (n=24, 23) | 16 Participants |
| FPV/RTV 700/100 mg BID + ABC/3TC FDC 600/300 mg QD | Number of Participants With HIV-1 RNA <400 Copies/mL (Primary Endpoint) at Week 48 Categorised by Baseline CD4+ Count, TLOVR Analysis | >=250 to <350 cell/mm3 (n=29, 31) | 26 Participants |
| FPV/RTV 700/100 mg BID + ABC/3TC FDC 600/300 mg QD | Number of Participants With HIV-1 RNA <400 Copies/mL (Primary Endpoint) at Week 48 Categorised by Baseline CD4+ Count, TLOVR Analysis | >=150 to <250 cells/mm3 (n=29, 31) | 26 Participants |
Secondary
Number of Participants With HIV-1 RNA <400 Copies/mL (Primary Endpoint) at Week 48 Categorised by Baseline Viral Load, TLOVR Analysis
The number of participants with HIV-1 RNA \<400 copies/mL at Week 48 was determined (by analysis of blood draw) and categorised by baseline viral load (BVL).
Time frame: Week 48
Population: ITT-E Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| FPV/RTV 1400/100 mg Once Daily (QD) + ABC/3TC FDC 600/300 mg Q | Number of Participants With HIV-1 RNA <400 Copies/mL (Primary Endpoint) at Week 48 Categorised by Baseline Viral Load, TLOVR Analysis | <50000 cp/mL (n=35, 40) | 26 Participants |
| FPV/RTV 1400/100 mg Once Daily (QD) + ABC/3TC FDC 600/300 mg Q | Number of Participants With HIV-1 RNA <400 Copies/mL (Primary Endpoint) at Week 48 Categorised by Baseline Viral Load, TLOVR Analysis | >=50000 to <100000 cp/mL (n=21, 19) | 18 Participants |
| FPV/RTV 1400/100 mg Once Daily (QD) + ABC/3TC FDC 600/300 mg Q | Number of Participants With HIV-1 RNA <400 Copies/mL (Primary Endpoint) at Week 48 Categorised by Baseline Viral Load, TLOVR Analysis | >=100000 to <200000 cp/mL (n=25, 17) | 21 Participants |
| FPV/RTV 1400/100 mg Once Daily (QD) + ABC/3TC FDC 600/300 mg Q | Number of Participants With HIV-1 RNA <400 Copies/mL (Primary Endpoint) at Week 48 Categorised by Baseline Viral Load, TLOVR Analysis | >=200000 cp/mL (n=25, 30) | 21 Participants |
| FPV/RTV 700/100 mg BID + ABC/3TC FDC 600/300 mg QD | Number of Participants With HIV-1 RNA <400 Copies/mL (Primary Endpoint) at Week 48 Categorised by Baseline Viral Load, TLOVR Analysis | >=200000 cp/mL (n=25, 30) | 24 Participants |
| FPV/RTV 700/100 mg BID + ABC/3TC FDC 600/300 mg QD | Number of Participants With HIV-1 RNA <400 Copies/mL (Primary Endpoint) at Week 48 Categorised by Baseline Viral Load, TLOVR Analysis | <50000 cp/mL (n=35, 40) | 37 Participants |
| FPV/RTV 700/100 mg BID + ABC/3TC FDC 600/300 mg QD | Number of Participants With HIV-1 RNA <400 Copies/mL (Primary Endpoint) at Week 48 Categorised by Baseline Viral Load, TLOVR Analysis | >=100000 to <200000 cp/mL (n=25, 17) | 11 Participants |
| FPV/RTV 700/100 mg BID + ABC/3TC FDC 600/300 mg QD | Number of Participants With HIV-1 RNA <400 Copies/mL (Primary Endpoint) at Week 48 Categorised by Baseline Viral Load, TLOVR Analysis | >=50000 to <100000 cp/mL (n=21, 19) | 15 Participants |
Secondary
Number of Protocol-defined Virological Failures With Genotypic and Phenotypic Resistance Changes
A blood sample was drawn at the time of confirmation of virological failure, and mutations present in the virus were identified and compared to those found in the blood sample at baseline. New mutations were tabulated by drug class. RT, reverse transcriptase. Virological failure could occur anytime from Week 4 to Week 48.
Time frame: Time to virologic failure; Week 4 up to Week 48
Population: Participants in the ITT-E Population who met the definition of virological failure
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| FPV/RTV 1400/100 mg Once Daily (QD) + ABC/3TC FDC 600/300 mg Q | Number of Protocol-defined Virological Failures With Genotypic and Phenotypic Resistance Changes | Treatment-Emergent Major HIV RT Mutations (M184V) | 1 Participants |
| FPV/RTV 1400/100 mg Once Daily (QD) + ABC/3TC FDC 600/300 mg Q | Number of Protocol-defined Virological Failures With Genotypic and Phenotypic Resistance Changes | Treatment-Emergent Major HIV Protease Mutations | 0 Participants |
| FPV/RTV 700/100 mg BID + ABC/3TC FDC 600/300 mg QD | Number of Protocol-defined Virological Failures With Genotypic and Phenotypic Resistance Changes | Treatment-Emergent Major HIV RT Mutations (M184V) | 0 Participants |
| FPV/RTV 700/100 mg BID + ABC/3TC FDC 600/300 mg QD | Number of Protocol-defined Virological Failures With Genotypic and Phenotypic Resistance Changes | Treatment-Emergent Major HIV Protease Mutations | 0 Participants |
Secondary
Percentage of Participants With HIV-1 RNA <50 and >=50 Copies/mL by Visit Over 48 Weeks
A blood sample was drawn to determine the amount of HIV-1 RNA virus in copies/mL at week 48. The percentage of participants with HIV-1 RNA \<50 copies/mL at Week 48 was determined by the TLOVR algorithm
Time frame: Week 48
Population: ITT-E Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| FPV/RTV 1400/100 mg Once Daily (QD) + ABC/3TC FDC 600/300 mg Q | Percentage of Participants With HIV-1 RNA <50 and >=50 Copies/mL by Visit Over 48 Weeks | HIV-1 RNA <50 copies/mL | 76 Percentage of participants |
| FPV/RTV 1400/100 mg Once Daily (QD) + ABC/3TC FDC 600/300 mg Q | Percentage of Participants With HIV-1 RNA <50 and >=50 Copies/mL by Visit Over 48 Weeks | HIV-1 RNA >=50 copies/mL | 24 Percentage of participants |
| FPV/RTV 700/100 mg BID + ABC/3TC FDC 600/300 mg QD | Percentage of Participants With HIV-1 RNA <50 and >=50 Copies/mL by Visit Over 48 Weeks | HIV-1 RNA <50 copies/mL | 77 Percentage of participants |
| FPV/RTV 700/100 mg BID + ABC/3TC FDC 600/300 mg QD | Percentage of Participants With HIV-1 RNA <50 and >=50 Copies/mL by Visit Over 48 Weeks | HIV-1 RNA >=50 copies/mL | 23 Percentage of participants |
Secondary
Steady-state Levels of Amprenavir (APV) and Ritonavir (RTV) Ctau at Weeks 4, 12, and 24
Blood samples were drawn at Weeks 4, 12, and 24 to determine plasma concentrations (Ctau) of APV and RTV
Time frame: Weeks 4, 12, and 24
Population: PK parameter (Ctau) Population - Participants in the ITT-E population who underwent PK sampling and had evaluable APV Ctau or RTV Ctau data
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| FPV/RTV 1400/100 mg Once Daily (QD) + ABC/3TC FDC 600/300 mg Q | Steady-state Levels of Amprenavir (APV) and Ritonavir (RTV) Ctau at Weeks 4, 12, and 24 | Week 4 APV Ctau | 1.11 micrograms/mL |
| FPV/RTV 1400/100 mg Once Daily (QD) + ABC/3TC FDC 600/300 mg Q | Steady-state Levels of Amprenavir (APV) and Ritonavir (RTV) Ctau at Weeks 4, 12, and 24 | Week 12 APV Ctau | 0.913 micrograms/mL |
| FPV/RTV 1400/100 mg Once Daily (QD) + ABC/3TC FDC 600/300 mg Q | Steady-state Levels of Amprenavir (APV) and Ritonavir (RTV) Ctau at Weeks 4, 12, and 24 | Week 24 APV Ctau | 1.08 micrograms/mL |
| FPV/RTV 1400/100 mg Once Daily (QD) + ABC/3TC FDC 600/300 mg Q | Steady-state Levels of Amprenavir (APV) and Ritonavir (RTV) Ctau at Weeks 4, 12, and 24 | Week 4 RTV Ctau | 0.0369 micrograms/mL |
| FPV/RTV 1400/100 mg Once Daily (QD) + ABC/3TC FDC 600/300 mg Q | Steady-state Levels of Amprenavir (APV) and Ritonavir (RTV) Ctau at Weeks 4, 12, and 24 | Week 12 RTV Ctau | 0.0285 micrograms/mL |
| FPV/RTV 1400/100 mg Once Daily (QD) + ABC/3TC FDC 600/300 mg Q | Steady-state Levels of Amprenavir (APV) and Ritonavir (RTV) Ctau at Weeks 4, 12, and 24 | Week 24 RTV Ctau | 0.0363 micrograms/mL |
| FPV/RTV 700/100 mg BID + ABC/3TC FDC 600/300 mg QD | Steady-state Levels of Amprenavir (APV) and Ritonavir (RTV) Ctau at Weeks 4, 12, and 24 | Week 12 RTV Ctau | 0.175 micrograms/mL |
| FPV/RTV 700/100 mg BID + ABC/3TC FDC 600/300 mg QD | Steady-state Levels of Amprenavir (APV) and Ritonavir (RTV) Ctau at Weeks 4, 12, and 24 | Week 4 APV Ctau | 1.99 micrograms/mL |
| FPV/RTV 700/100 mg BID + ABC/3TC FDC 600/300 mg QD | Steady-state Levels of Amprenavir (APV) and Ritonavir (RTV) Ctau at Weeks 4, 12, and 24 | Week 4 RTV Ctau | 0.166 micrograms/mL |
| FPV/RTV 700/100 mg BID + ABC/3TC FDC 600/300 mg QD | Steady-state Levels of Amprenavir (APV) and Ritonavir (RTV) Ctau at Weeks 4, 12, and 24 | Week 12 APV Ctau | 1.87 micrograms/mL |
| FPV/RTV 700/100 mg BID + ABC/3TC FDC 600/300 mg QD | Steady-state Levels of Amprenavir (APV) and Ritonavir (RTV) Ctau at Weeks 4, 12, and 24 | Week 24 RTV Ctau | 0.170 micrograms/mL |
| FPV/RTV 700/100 mg BID + ABC/3TC FDC 600/300 mg QD | Steady-state Levels of Amprenavir (APV) and Ritonavir (RTV) Ctau at Weeks 4, 12, and 24 | Week 24 APV Ctau | 2.00 micrograms/mL |
Secondary
Study Endpoints for a Subset of Subjects Receiving Study Drug Beyond 48 Weeks
Adaptive two-stage design study up to 48 weeks. N=200, expanding to 728 if continuation criteria were achieved based on a 24-week interim analysis. The initial 200 participants would continue until the last subject of the expanded cohort reached 48 weeks and would constitute the subset. As continuation criteria were not achieved, the study did not proceed to the second stage, and full analysis was performed on the initial 200 participants only.
Time frame: Up to 60 weeks