Trial Outcomes & Findings for HIV-1 Infection Study of Once a Day Versus Twice a Day Protease Inhibitor in Antiretroviral Treatment Naive Adults (NCT NCT00450580)

Last Updated: 2012-06-07

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

212 participants

Primary outcome timeframe

Week 48

Results posted on

2012-06-07

Participant Flow

Participant milestones

Participant milestones
Measure	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	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
Overall Study STARTED	106	106
Overall Study COMPLETED	90	90
Overall Study NOT COMPLETED	16	16

Reasons for withdrawal

Reasons for withdrawal
Measure	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	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
Overall Study Adverse Event	5	7
Overall Study Lost to Follow-up	4	5
Overall Study Withdrawal by Subject	2	2
Overall Study Protocol Violation	1	1
Overall Study Protocol-defined virologic failure	1	0
Overall Study Could not comply with scheduled visits	1	0
Overall Study Patient went to Brazil	1	0
Overall Study Patient could not swallow Norvir	1	0
Overall Study Withdrawal due to pregnancy	0	1

Baseline Characteristics

HIV-1 Infection Study of Once a Day Versus Twice a Day Protease Inhibitor in Antiretroviral Treatment Naive Adults

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	FPV/RTV 1400/100 mg Once Daily (QD) + ABC/3TC FDC 600/300 mg Q n=106 Participants 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	FPV/RTV 700/100 mg BID + ABC/3TC FDC 600/300 mg QD n=106 Participants FPV/RTV 700 mg/100 mg twice daily administered with ABC/3TC FDC 600/300 mg once daily	Total n=212 Participants Total of all reporting groups
Age, Customized	37 years n=93 Participants	38 years n=4 Participants	38 years n=27 Participants
Sex: Female, Male Female	27 Participants n=93 Participants	29 Participants n=4 Participants	56 Participants n=27 Participants
Sex: Female, Male Male	79 Participants n=93 Participants	77 Participants n=4 Participants	156 Participants n=27 Participants
Race/Ethnicity, Customized African American/African heritage	23 participants n=93 Participants	22 participants n=4 Participants	45 participants n=27 Participants
Race/Ethnicity, Customized American Indian/Alaskan native	3 participants n=93 Participants	3 participants n=4 Participants	6 participants n=27 Participants
Race/Ethnicity, Customized Asian - South East Asian	2 participants n=93 Participants	2 participants n=4 Participants	4 participants n=27 Participants
Race/Ethnicity, Customized White - Arabic/North African	1 participants n=93 Participants	1 participants n=4 Participants	2 participants n=27 Participants
Race/Ethnicity, Customized White - White/Caucasian/European	75 participants n=93 Participants	78 participants n=4 Participants	153 participants n=27 Participants
Race/Ethnicity, Customized Mixed race	2 participants n=93 Participants	0 participants n=4 Participants	2 participants n=27 Participants

PRIMARY outcome

Timeframe: Week 48

Population: Intent-to-Treat-Exposed (ITT-E) Population: All randomised participants who received at least one dose of study medication

Outcome measures

Outcome measures
Measure	FPV/RTV 1400/100 mg Once Daily (QD) + ABC/3TC FDC 600/300 mg Q n=106 Participants 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	FPV/RTV 700/100 mg BID + ABC/3TC FDC 600/300 mg QD n=106 Participants FPV/RTV 700 mg/100 mg twice daily administered with ABC/3TC FDC 600/300 mg once daily
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	82 Percentage of participants
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	18 Percentage of participants

SECONDARY outcome

Timeframe: Week 48

Population: ITT-E Population

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

Outcome measures

Outcome measures
Measure	FPV/RTV 1400/100 mg Once Daily (QD) + ABC/3TC FDC 600/300 mg Q n=106 Participants 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	FPV/RTV 700/100 mg BID + ABC/3TC FDC 600/300 mg QD n=106 Participants FPV/RTV 700 mg/100 mg twice daily administered with ABC/3TC FDC 600/300 mg once daily
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	77 Percentage of participants
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	23 Percentage of participants

SECONDARY outcome

Timeframe: Week 48

Population: ITT-E Population

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).

Outcome measures

Outcome measures
Measure	FPV/RTV 1400/100 mg Once Daily (QD) + ABC/3TC FDC 600/300 mg Q n=106 Participants 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	FPV/RTV 700/100 mg BID + ABC/3TC FDC 600/300 mg QD n=106 Participants FPV/RTV 700 mg/100 mg twice daily administered with ABC/3TC FDC 600/300 mg once daily
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	37 Participants
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	15 Participants
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	11 Participants
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	24 Participants

SECONDARY outcome

Timeframe: Week 48

Population: ITT-E Population

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.

Outcome measures

Outcome measures
Measure	FPV/RTV 1400/100 mg Once Daily (QD) + ABC/3TC FDC 600/300 mg Q n=106 Participants 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	FPV/RTV 700/100 mg BID + ABC/3TC FDC 600/300 mg QD n=106 Participants FPV/RTV 700 mg/100 mg twice daily administered with ABC/3TC FDC 600/300 mg once daily
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	19 Participants
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	16 Participants
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	26 Participants
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	26 Participants

SECONDARY outcome

Timeframe: Week 48

Population: Safety Population: all participants who received at least one dose of study medication

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.

Outcome measures

Outcome measures
Measure	FPV/RTV 1400/100 mg Once Daily (QD) + ABC/3TC FDC 600/300 mg Q n=77 Participants 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	FPV/RTV 700/100 mg BID + ABC/3TC FDC 600/300 mg QD n=80 Participants FPV/RTV 700 mg/100 mg twice daily administered with ABC/3TC FDC 600/300 mg once daily
Change From Baseline in Non-HDL Cholesterol at Week 48	1.10 mmol/L (millimoles/Liter) Standard Deviation 0.81	1.26 mmol/L (millimoles/Liter) Standard Deviation 0.90

SECONDARY outcome

Timeframe: Time to virologic failure; Week 4 up to Week 48

Population: Participants in the ITT-E Population who met the definition of virological failure

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.

Outcome measures

Outcome measures
Measure	FPV/RTV 1400/100 mg Once Daily (QD) + ABC/3TC FDC 600/300 mg Q n=2 Participants 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	FPV/RTV 700/100 mg BID + ABC/3TC FDC 600/300 mg QD n=1 Participants FPV/RTV 700 mg/100 mg twice daily administered with ABC/3TC FDC 600/300 mg once daily
Number of Protocol-defined Virological Failures With Genotypic and Phenotypic Resistance Changes Treatment-Emergent Major HIV RT Mutations (M184V)	1 Participants	0 Participants
Number of Protocol-defined Virological Failures With Genotypic and Phenotypic Resistance Changes Treatment-Emergent Major HIV Protease Mutations	0 Participants	0 Participants

SECONDARY outcome

Timeframe: 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

Blood samples were drawn at Weeks 4, 12, and 24 to determine plasma concentrations (Ctau) of APV and RTV

Outcome measures

Outcome measures
Measure	FPV/RTV 1400/100 mg Once Daily (QD) + ABC/3TC FDC 600/300 mg Q n=79 Participants 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	FPV/RTV 700/100 mg BID + ABC/3TC FDC 600/300 mg QD n=97 Participants FPV/RTV 700 mg/100 mg twice daily administered with ABC/3TC FDC 600/300 mg once daily
Steady-state Levels of Amprenavir (APV) and Ritonavir (RTV) Ctau at Weeks 4, 12, and 24 Week 4 RTV Ctau	0.0369 micrograms/mL Interval 0.0264 to 0.0516	0.166 micrograms/mL Interval 0.137 to 0.201
Steady-state Levels of Amprenavir (APV) and Ritonavir (RTV) Ctau at Weeks 4, 12, and 24 Week 4 APV Ctau	1.11 micrograms/mL Interval 0.909 to 1.35	1.99 micrograms/mL Interval 1.76 to 2.26
Steady-state Levels of Amprenavir (APV) and Ritonavir (RTV) Ctau at Weeks 4, 12, and 24 Week 12 RTV Ctau	0.0285 micrograms/mL Interval 0.0215 to 0.0379	0.175 micrograms/mL Interval 0.15 to 0.205
Steady-state Levels of Amprenavir (APV) and Ritonavir (RTV) Ctau at Weeks 4, 12, and 24 Week 24 RTV Ctau	0.0363 micrograms/mL Interval 0.0241 to 0.0545	0.170 micrograms/mL Interval 0.143 to 0.202
Steady-state Levels of Amprenavir (APV) and Ritonavir (RTV) Ctau at Weeks 4, 12, and 24 Week 12 APV Ctau	0.913 micrograms/mL Interval 0.747 to 1.17	1.87 micrograms/mL Interval 1.66 to 2.12
Steady-state Levels of Amprenavir (APV) and Ritonavir (RTV) Ctau at Weeks 4, 12, and 24 Week 24 APV Ctau	1.08 micrograms/mL Interval 0.869 to 1.34	2.00 micrograms/mL Interval 1.78 to 2.25

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome data not reported

Adverse Events

FPV/RTV 1400/100 mg Once Daily (QD) + ABC/3TC FDC 600/300 mg Q

Serious events: 19 serious events

Other events: 79 other events

Deaths: 0 deaths

FPV/RTV 700/100 mg BID + ABC/3TC FDC 600/300 mg QD

Serious events: 18 serious events

Other events: 72 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	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	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
Immune system disorders Drug Hypersensitivity	14.2% 15/106	7.5% 8/106
Infections and infestations Pneumonia	1.9% 2/106	0.94% 1/106
Immune system disorders Immune reconstitution syndrome	0.00% 0/106	0.94% 1/106
Infections and infestations Atypical mycobacterial infection	0.00% 0/106	0.94% 1/106
Infections and infestations Cat scratch disease	0.00% 0/106	0.94% 1/106
Infections and infestations Hepatitis C	0.00% 0/106	0.94% 1/106
Infections and infestations Mycobacterium avium complex infection	0.00% 0/106	0.94% 1/106
Infections and infestations Respiratory tract infection	0.00% 0/106	0.94% 1/106
Infections and infestations Sepsis	0.94% 1/106	0.00% 0/106
Infections and infestations Staphylococcal sepsis	0.00% 0/106	0.94% 1/106
Infections and infestations Superinfection	0.00% 0/106	0.94% 1/106
Cardiac disorders Angina pectoris	0.94% 1/106	0.00% 0/106
Cardiac disorders Myocardial infarction	0.00% 0/106	0.94% 1/106
Investigations Alanine aminotransferase increased	0.00% 0/106	0.94% 1/106
Investigations Aspartate aminotransferase increased	0.94% 1/106	0.00% 0/106
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	0.94% 1/106	0.00% 0/106
Respiratory, thoracic and mediastinal disorders Lung disorder	0.00% 0/106	0.94% 1/106
Blood and lymphatic system disorders Lymphadenopathy	0.00% 0/106	0.94% 1/106
Gastrointestinal disorders Pancreatitis	0.94% 1/106	0.00% 0/106
Hepatobiliary disorders Hepatitis acute	0.00% 0/106	0.94% 1/106
Metabolism and nutrition disorders Diabetes mellitus inadequate control	0.94% 1/106	0.00% 0/106
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Burkitt's lymphoma	0.94% 1/106	0.00% 0/106
Nervous system disorders Facial paresis	0.94% 1/106	0.00% 0/106
Psychiatric disorders Depression	0.00% 0/106	0.94% 1/106

Other adverse events

Other adverse events
Measure	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	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
Skin and subcutaneous tissue disorders Rash	10.4% 11/106	12.3% 13/106
Metabolism and nutrition disorders Hypercholesterolaemia	5.7% 6/106	7.5% 8/106
Gastrointestinal disorders Vomiting	7.5% 8/106	4.7% 5/106
General disorders Fatigue	6.6% 7/106	5.7% 6/106
Gastrointestinal disorders Dyspepsia	4.7% 5/106	1.9% 2/106
Metabolism and nutrition disorders Hypertriglyceridaemia	1.9% 2/106	8.5% 9/106
Gastrointestinal disorders Diarrhoea	42.5% 45/106	46.2% 49/106
Gastrointestinal disorders Nausea	17.0% 18/106	8.5% 9/106
Infections and infestations Nasopharyngitis	17.0% 18/106	6.6% 7/106
Immune system disorders Drug hypersensitivity	14.2% 15/106	7.5% 8/106

Additional Information

GSK Response Center

GlaxoSmithKline

Phone: 866-435-7343

Results disclosure agreements

Principal investigator is a sponsor employee GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
Publication restrictions are in place

Restriction type: OTHER