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

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ClinicalTrials.gov Identifier: NCT00450580
Recruitment Status : Completed
First Posted : March 22, 2007
Results First Posted : September 2, 2009
Last Update Posted : June 7, 2012
Sponsor:
Collaborator:
GlaxoSmithKline
Information provided by (Responsible Party):
ViiV Healthcare

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Infection, Human Immunodeficiency Virus I
HIV-1 Infection
Intervention Drug: fosamprenavir/ritonavir
Enrollment 212
Recruitment Details  
Pre-assignment Details  
Arm/Group Title FPV/RTV 1400/100 mg Once Daily (QD) + ABC/3TC FDC 600/300 mg Q FPV/RTV 700/100 mg BID + ABC/3TC FDC 600/300 mg QD
Hide Arm/Group Description 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 mg/100 mg twice daily administered with ABC/3TC FDC 600/300 mg once daily
Period Title: Overall Study
Started 106 106
Completed 90 90
Not Completed 16 16
Reason Not Completed
Adverse Event             5             7
Lost to Follow-up             4             5
Withdrawal by Subject             2             2
Protocol Violation             1             1
Protocol-defined virologic failure             1             0
Could not comply with scheduled visits             1             0
Patient went to Brazil             1             0
Patient could not swallow Norvir             1             0
Withdrawal due to pregnancy             0             1
Arm/Group Title FPV/RTV 1400/100 mg Once Daily (QD) + ABC/3TC FDC 600/300 mg Q FPV/RTV 700/100 mg BID + ABC/3TC FDC 600/300 mg QD Total
Hide Arm/Group Description 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 mg/100 mg twice daily administered with ABC/3TC FDC 600/300 mg once daily Total of all reporting groups
Overall Number of Baseline Participants 106 106 212
Hide Baseline Analysis Population Description
[Not Specified]
Age, Customized  
Mean (Full Range)
Unit of measure:  Years
Number Analyzed 106 participants 106 participants 212 participants
37
(18 to 70)
38
(19 to 69)
38
(18 to 70)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 106 participants 106 participants 212 participants
Female
27
  25.5%
29
  27.4%
56
  26.4%
Male
79
  74.5%
77
  72.6%
156
  73.6%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 106 participants 106 participants 212 participants
African American/African heritage 23 22 45
American Indian/Alaskan native 3 3 6
Asian - South East Asian 2 2 4
White - Arabic/North African 1 1 2
White - White/Caucasian/European 75 78 153
Mixed race 2 0 2
1.Primary Outcome
Title Percentage of Participants With HIV-1 RNA <400 and >=400 Copies/mL Over 48 Weeks
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat-Exposed (ITT-E) Population: All randomised participants who received at least one dose of study medication
Arm/Group Title FPV/RTV 1400/100 mg Once Daily (QD) + ABC/3TC FDC 600/300 mg Q FPV/RTV 700/100 mg BID + ABC/3TC FDC 600/300 mg QD
Hide Arm/Group Description:
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 mg/100 mg twice daily administered with ABC/3TC FDC 600/300 mg once daily
Overall Number of Participants Analyzed 106 106
Measure Type: Number
Unit of Measure: Percentage of participants
HIV-1 RNA <400 copies/mL 81 82
HIV-1 RNA >=400 copies/mL 19 18
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection FPV/RTV 1400/100 mg Once Daily (QD) + ABC/3TC FDC 600/300 mg Q, FPV/RTV 700/100 mg BID + ABC/3TC FDC 600/300 mg QD
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments Non-inferiority can be concluded if the lower bound of a two-sided 95% confidence interval for the difference in response rates between the two treatment arms is greater than -12%.
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value -0.9
Confidence Interval 95%
-11.4 to 9.5
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Percentage of Participants With HIV-1 RNA <50 and >=50 Copies/mL by Visit Over 48 Weeks
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
ITT-E Population
Arm/Group Title FPV/RTV 1400/100 mg Once Daily (QD) + ABC/3TC FDC 600/300 mg Q FPV/RTV 700/100 mg BID + ABC/3TC FDC 600/300 mg QD
Hide Arm/Group Description:
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 mg/100 mg twice daily administered with ABC/3TC FDC 600/300 mg once daily
Overall Number of Participants Analyzed 106 106
Measure Type: Number
Unit of Measure: Percentage of participants
HIV-1 RNA <50 copies/mL 76 77
HIV-1 RNA >=50 copies/mL 24 23
3.Secondary Outcome
Title Number of Participants With HIV-1 RNA <400 Copies/mL (Primary Endpoint) at Week 48 Categorised by Baseline Viral Load, TLOVR Analysis
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
ITT-E Population
Arm/Group Title FPV/RTV 1400/100 mg Once Daily (QD) + ABC/3TC FDC 600/300 mg Q FPV/RTV 700/100 mg BID + ABC/3TC FDC 600/300 mg QD
Hide Arm/Group Description:
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 mg/100 mg twice daily administered with ABC/3TC FDC 600/300 mg once daily
Overall Number of Participants Analyzed 106 106
Measure Type: Number
Unit of Measure: Participants
<50000 cp/mL (n=35, 40) 26 37
>=50000 to <100000 cp/mL (n=21, 19) 18 15
>=100000 to <200000 cp/mL (n=25, 17) 21 11
>=200000 cp/mL (n=25, 30) 21 24
4.Secondary Outcome
Title Number of Participants With HIV-1 RNA <400 Copies/mL (Primary Endpoint) at Week 48 Categorised by Baseline CD4+ Count, TLOVR Analysis
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
ITT-E Population
Arm/Group Title FPV/RTV 1400/100 mg Once Daily (QD) + ABC/3TC FDC 600/300 mg Q FPV/RTV 700/100 mg BID + ABC/3TC FDC 600/300 mg QD
Hide Arm/Group Description:
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 mg/100 mg twice daily administered with ABC/3TC FDC 600/300 mg once daily
Overall Number of Participants Analyzed 106 106
Measure Type: Number
Unit of Measure: Participants
<150 cells/mm3 (n=24, 23) 18 16
>=150 to <250 cells/mm3 (n=29, 31) 24 26
>=250 to <350 cell/mm3 (n=29, 31) 23 26
>=350 cell/mm3 (n=24, 21) 21 19
5.Secondary Outcome
Title Change From Baseline in Non-HDL Cholesterol at Week 48
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population: all participants who received at least one dose of study medication
Arm/Group Title FPV/RTV 1400/100 mg Once Daily (QD) + ABC/3TC FDC 600/300 mg Q FPV/RTV 700/100 mg BID + ABC/3TC FDC 600/300 mg QD
Hide Arm/Group Description:
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 mg/100 mg twice daily administered with ABC/3TC FDC 600/300 mg once daily
Overall Number of Participants Analyzed 77 80
Mean (Standard Deviation)
Unit of Measure: mmol/L (millimoles/Liter)
1.10  (0.81) 1.26  (0.90)
6.Secondary Outcome
Title Number of Protocol-defined Virological Failures With Genotypic and Phenotypic Resistance Changes
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the ITT-E Population who met the definition of virological failure
Arm/Group Title FPV/RTV 1400/100 mg Once Daily (QD) + ABC/3TC FDC 600/300 mg Q FPV/RTV 700/100 mg BID + ABC/3TC FDC 600/300 mg QD
Hide Arm/Group Description:
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 mg/100 mg twice daily administered with ABC/3TC FDC 600/300 mg once daily
Overall Number of Participants Analyzed 2 1
Measure Type: Number
Unit of Measure: Participants
Treatment-Emergent Major HIV RT Mutations (M184V) 1 0
Treatment-Emergent Major HIV Protease Mutations 0 0
7.Secondary Outcome
Title Steady-state Levels of Amprenavir (APV) and Ritonavir (RTV) Ctau at Weeks 4, 12, and 24
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
PK parameter (Ctau) Population - Participants in the ITT-E population who underwent PK sampling and had evaluable APV Ctau or RTV Ctau data
Arm/Group Title FPV/RTV 1400/100 mg Once Daily (QD) + ABC/3TC FDC 600/300 mg Q FPV/RTV 700/100 mg BID + ABC/3TC FDC 600/300 mg QD
Hide Arm/Group Description:
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 mg/100 mg twice daily administered with ABC/3TC FDC 600/300 mg once daily
Overall Number of Participants Analyzed 79 97
Geometric Mean (95% Confidence Interval)
Unit of Measure: micrograms/mL
Week 4 APV Ctau
1.11
(0.909 to 1.35)
1.99
(1.76 to 2.26)
Week 12 APV Ctau
0.913
(0.747 to 1.17)
1.87
(1.66 to 2.12)
Week 24 APV Ctau
1.08
(0.869 to 1.34)
2.00
(1.78 to 2.25)
Week 4 RTV Ctau
0.0369
(0.0264 to 0.0516)
0.166
(0.137 to 0.201)
Week 12 RTV Ctau
0.0285
(0.0215 to 0.0379)
0.175
(0.150 to 0.205)
Week 24 RTV Ctau
0.0363
(0.0241 to 0.0545)
0.170
(0.143 to 0.202)
8.Secondary Outcome
Title Study Endpoints for a Subset of Subjects Receiving Study Drug Beyond 48 Weeks
Hide Description 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
Outcome Measure Data Not Reported
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title FPV/RTV 1400/100 mg Once Daily (QD) + ABC/3TC FDC 600/300 mg Q FPV/RTV 700/100 mg BID + ABC/3TC FDC 600/300 mg QD
Hide Arm/Group Description 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 mg/100 mg twice daily administered with ABC/3TC FDC 600/300 mg once daily
All-Cause Mortality
FPV/RTV 1400/100 mg Once Daily (QD) + ABC/3TC FDC 600/300 mg Q FPV/RTV 700/100 mg BID + ABC/3TC FDC 600/300 mg QD
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Hide Serious Adverse Events
FPV/RTV 1400/100 mg Once Daily (QD) + ABC/3TC FDC 600/300 mg Q FPV/RTV 700/100 mg BID + ABC/3TC FDC 600/300 mg QD
Affected / at Risk (%) Affected / at Risk (%)
Total   19   18 
Blood and lymphatic system disorders     
Lymphadenopathy  1  0/106 (0.00%)  1/106 (0.94%) 
Cardiac disorders     
Angina pectoris  1  1/106 (0.94%)  0/106 (0.00%) 
Myocardial infarction  1  0/106 (0.00%)  1/106 (0.94%) 
Gastrointestinal disorders     
Pancreatitis  1  1/106 (0.94%)  0/106 (0.00%) 
Hepatobiliary disorders     
Hepatitis acute  1  0/106 (0.00%)  1/106 (0.94%) 
Immune system disorders     
Drug Hypersensitivity  1  15/106 (14.15%)  8/106 (7.55%) 
Immune reconstitution syndrome  1  0/106 (0.00%)  1/106 (0.94%) 
Infections and infestations     
Pneumonia  1  2/106 (1.89%)  1/106 (0.94%) 
Atypical mycobacterial infection  1  0/106 (0.00%)  1/106 (0.94%) 
Cat scratch disease  1  0/106 (0.00%)  1/106 (0.94%) 
Hepatitis C  1  0/106 (0.00%)  1/106 (0.94%) 
Mycobacterium avium complex infection  1  0/106 (0.00%)  1/106 (0.94%) 
Respiratory tract infection  1  0/106 (0.00%)  1/106 (0.94%) 
Sepsis  1  1/106 (0.94%)  0/106 (0.00%) 
Staphylococcal sepsis  1  0/106 (0.00%)  1/106 (0.94%) 
Superinfection  1  0/106 (0.00%)  1/106 (0.94%) 
Investigations     
Alanine aminotransferase increased  1  0/106 (0.00%)  1/106 (0.94%) 
Aspartate aminotransferase increased  1  1/106 (0.94%)  0/106 (0.00%) 
Metabolism and nutrition disorders     
Diabetes mellitus inadequate control  1  1/106 (0.94%)  0/106 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Burkitt's lymphoma  1  1/106 (0.94%)  0/106 (0.00%) 
Nervous system disorders     
Facial paresis  1  1/106 (0.94%)  0/106 (0.00%) 
Psychiatric disorders     
Depression  1  0/106 (0.00%)  1/106 (0.94%) 
Respiratory, thoracic and mediastinal disorders     
Chronic obstructive pulmonary disease  1  1/106 (0.94%)  0/106 (0.00%) 
Lung disorder  1  0/106 (0.00%)  1/106 (0.94%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
FPV/RTV 1400/100 mg Once Daily (QD) + ABC/3TC FDC 600/300 mg Q FPV/RTV 700/100 mg BID + ABC/3TC FDC 600/300 mg QD
Affected / at Risk (%) Affected / at Risk (%)
Total   79   72 
Gastrointestinal disorders     
Diarrhoea  1  45/106 (42.45%)  49/106 (46.23%) 
Nausea  1  18/106 (16.98%)  9/106 (8.49%) 
Vomiting  1  8/106 (7.55%)  5/106 (4.72%) 
Dyspepsia  1  5/106 (4.72%)  2/106 (1.89%) 
General disorders     
Fatigue  1  7/106 (6.60%)  6/106 (5.66%) 
Immune system disorders     
Drug hypersensitivity  1  15/106 (14.15%)  8/106 (7.55%) 
Infections and infestations     
Nasopharyngitis  1  18/106 (16.98%)  7/106 (6.60%) 
Metabolism and nutrition disorders     
Hypercholesterolaemia  1  6/106 (5.66%)  8/106 (7.55%) 
Hypertriglyceridaemia  1  2/106 (1.89%)  9/106 (8.49%) 
Skin and subcutaneous tissue disorders     
Rash  1  11/106 (10.38%)  13/106 (12.26%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
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.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: GSK Response Center
Organization: GlaxoSmithKline
Phone: 866-435-7343
Publications:
Ross LL, Robinson MD, Carosi G, et al. Impact of HIV subtype on response and resistance in antiretroviral-naïve adults comparing treatment with once daily versus twice daily Ritonavir boosted Fosamprenavir in combination with Abacavir/Lamivudine. [Drugs Ther Stud]. 2012;2(e1):
Carosi G, Lazzarin A, Stellbrink H, et al. Efficacy and Safety of Fosamprenavir + Ritonavir (FPV/RTV) 700mg/100mg Twice Daily (BID) Versus FPV/RTV 1400mg/100mg Once Daily (QD) with ABC/3TC QD over 24 Weeks. Abstract H-1244, 48th Interscience Conference on Antimicrobial Agents and Chemotherapy, Washington, DC, 2008.
Layout table for additonal information
Responsible Party: ViiV Healthcare
ClinicalTrials.gov Identifier: NCT00450580    
Other Study ID Numbers: APV109141
First Submitted: March 21, 2007
First Posted: March 22, 2007
Results First Submitted: July 24, 2009
Results First Posted: September 2, 2009
Last Update Posted: June 7, 2012