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A Study of an Investigational Regimen Combining FDA Approved HIV Drugs in HIV-Infected Subjects

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ClinicalTrials.gov Identifier: NCT00363142
Recruitment Status : Completed
First Posted : August 15, 2006
Results First Posted : September 24, 2009
Last Update Posted : November 5, 2010
Sponsor:
Information provided by:
GlaxoSmithKline

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions HIV Infection
Infection, Human Immunodeficiency Virus
Interventions Drug: Half-boosted Fosamprenavir
Drug: Full Boosted Fosamprenavir
Enrollment 211
Recruitment Details  
Pre-assignment Details Participants were stratified prior to randomization according to baseline regimen (700 milligrams [mg]/100 mg twice a day [BID] or 1400 mg/200 mg once a day [QD]) and previous regimen (no other prior protease inhibitor [PI], non-boosted PI, or boosted PI). Results are reported for the 209 participants (out of 211 enrolled) receiving study drug.
Arm/Group Title FPV/r100 FPV/r200
Hide Arm/Group Description Fosamprenavir (FPV)/ritonavir (RTV) 1400mg/100mg once a day (QD) FPV/RTV (either 700mg/100mg twice a day [BID] or 1400mg/200mg QD)
Period Title: Overall Study
Started 140 69
Completed 133 66
Not Completed 7 3
Reason Not Completed
Adverse Event             2             0
Lack of Efficacy             0             1
Lost to Follow-up             1             0
Non-compliance             1             1
Withdrawal by Subject             3             1
Arm/Group Title FPV/r100 FPV/r200 Total
Hide Arm/Group Description Fosamprenavir (FPV)/ritonavir (RTV) 1400mg/100mg once a day (QD) FPV/RTV (either 700mg/100mg twice a day [BID] or 1400mg/200mg QD) Total of all reporting groups
Overall Number of Baseline Participants 140 69 209
Hide Baseline Analysis Population Description
[Not Specified]
Age Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 140 participants 69 participants 209 participants
44.9  (10.52) 44.3  (8.9) 44.7  (10.00)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 140 participants 69 participants 209 participants
Female
33
  23.6%
9
  13.0%
42
  20.1%
Male
107
  76.4%
60
  87.0%
167
  79.9%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 140 participants 69 participants 209 participants
African American/African heritage 42 20 62
American Indian/Alaskan native 1 0 1
Asian - South East Asian 0 2 2
Native Hawaiian or Other Pacific Islander 0 1 1
White - Arabic/North African 0 2 2
White - White/Caucasian/European 95 44 139
Mixed race 1 0 1
Other 1 0 1
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 140 participants 69 participants 209 participants
Hispanic or Latino
31
  22.1%
11
  15.9%
42
  20.1%
Not Hispanic or Latino
109
  77.9%
58
  84.1%
167
  79.9%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
1.Primary Outcome
Title Percentage of Participants Not Meeting the Definition of Virologic Failure at or Prior to Week 24
Hide Description Virologic failure was defined as two consecutive plasma HIV-1 RNA measures greater than 400 copies/milliliter (mL) separated by at least 2 to 4 week. The percentage of participants not meeting the virologic failure definition was estimated with stratification by the six randomization strata using Mantel-Haenszel weights and the missing/discontinuation equals failure (MD=F) analysis. Missing/discontinuation values were considered failures.
Time Frame Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat Exposed (ITT-E) Population. Subjects who received at least one dose of investigational product.
Arm/Group Title FPV/r100 FPV/r200
Hide Arm/Group Description:
Fosamprenavir (FPV)/ritonavir (RTV) 1400mg/100mg once a day (QD)
FPV/RTV (either 700mg/100mg twice a day [BID] or 1400mg/200mg QD)
Overall Number of Participants Analyzed 140 69
Measure Type: Number
Unit of Measure: Percentage of participants
92.1 94.2
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection FPV/r100, FPV/r200
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments Non-inferiority of FPV/r100 to FPV/r200 would be declared if the lower limit of the 2-sided 95% confidence interval on the difference in percentage of participants not meeting the virologic failure definition [FPV/r100 minus FPV/r200] was -12% or greater.
Method of Estimation Estimation Parameter Difference in the percentages
Estimated Value -2.12
Confidence Interval 95%
-9.36 to 5.12
Estimation Comments Difference in percentages = percentage in Arm 1 minus percentage in Arm 2
2.Secondary Outcome
Title Percentage of Participants With Plasma Human Immunodeficiency Virus, Type 1, Ribonucleic Acid (HIV-1 RNA) <400 Copies/mL at Week 24, Time to Loss of Virologic Response (TLOVR) Analysis
Hide Description A blood sample was drawn to determine the amount of plasma HIV-1 RNA virus in copies/mL at week 24. The percentage of participants with plasma HIV-1 RNA <400 copies/mL at Week 24 were determined by the TLOVR algorithm with stratification by the six randomization strata.
Time Frame Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
ITT-E Population
Arm/Group Title FPV/r100 FPV/r200
Hide Arm/Group Description:
Fosamprenavir (FPV)/ritonavir (RTV) 1400mg/100mg once a day (QD)
FPV/RTV (either 700mg/100mg twice a day [BID] or 1400mg/200mg QD)
Overall Number of Participants Analyzed 140 69
Measure Type: Number
Unit of Measure: Percentage of participants
Plasma HIV-1 RNA <400 copies/mL 92 94.2
HIV-1 RNA greater than or equal to 400 copies/mL 8 5.8
3.Secondary Outcome
Title Percentage of Participants With Plasma HIV-1 RNA <50 Copies/mL at Week 24, TLOVR Analysis
Hide Description A blood sample was drawn to determine the amount of plasma HIV-1 RNA virus in copies/mL at week 24. The percentage of participants plasma with HIV-1 RNA <50 copies/mL at Week 24 were determined by the TLOVR algorithm with stratification by the six randomization strata.
Time Frame Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
ITT-E Population
Arm/Group Title FPV/r100 FPV/r200
Hide Arm/Group Description:
Fosamprenavir (FPV)/ritonavir (RTV) 1400mg/100mg once a day (QD)
FPV/RTV (either 700mg/100mg twice a day [BID] or 1400mg/200mg QD)
Overall Number of Participants Analyzed 140 69
Measure Type: Number
Unit of Measure: Percentage of participants
Plasma HIV-1 RNA <50 copies/mL 82.9 84.6
HIV-1 RNA greater than or equal to 50 copies/mL 17.1 15.4
4.Secondary Outcome
Title Mean Change From Baseline of log10 Copies/mL Plasma HIV-1 RNA Levels at Week 24, Observed Analysis
Hide Description A blood sample was drawn to determine the amount of plasma HIV-1 RNA virus in copies/mL at week 24. Change from baseline was defined as plasma HIV-1 RNA level at Week 24 minus plasma HIV-1 RNA level at baseline.
Time Frame Baseline and Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
ITT-E Population - Observed Analysis, available data from those subjects who had values at baseline and at Week 24
Arm/Group Title FPV/r100 FPV/r200
Hide Arm/Group Description:
Fosamprenavir (FPV)/ritonavir (RTV) 1400mg/100mg once a day (QD)
FPV/RTV (either 700mg/100mg twice a day [BID] or 1400mg/200mg QD)
Overall Number of Participants Analyzed 131 66
Mean (Standard Deviation)
Unit of Measure: log10 copies/mL
-0.015  (0.388) -0.022  (0.130)
5.Secondary Outcome
Title Median Change From Baseline of CD4+ Cell Count at Week 24, Observed Analysis
Hide Description A blood sample was drawn to determine the CD4+ cell count at week 24. Change from baseline was defined as CD4+ cell count at Week 24 minus CD4+ cell count at baseline.
Time Frame Baseline and Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
ITT-E Population - Observed Analysis, available data from those subjects who had values at baseline and at Week 24
Arm/Group Title FPV/r100 FPV/r200
Hide Arm/Group Description:
Fosamprenavir (FPV)/ritonavir (RTV) 1400mg/100mg once a day (QD)
FPV/RTV (either 700mg/100mg twice a day [BID] or 1400mg/200mg QD)
Overall Number of Participants Analyzed 132 67
Median (Full Range)
Unit of Measure: cells/mm3
11.5
(-386 to 407)
15
(-201 to 454)
6.Secondary Outcome
Title Number of Participants Who Discontinued Treatment Due to Adverse Events Through Week 24
Hide Description The number of participants who prematurely discontinued study drug due to adverse events was tabulated. Data are summarized by individual adverse event. Adverse events were defined as any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
Time Frame Baseline through Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population: all randomized subjects who consumed at least one dose of study drug and was analyzed according to the treatment received.
Arm/Group Title FPV/r100 FPV/r200
Hide Arm/Group Description:
Fosamprenavir (FPV)/ritonavir (RTV) 1400mg/100mg once a day (QD)
FPV/RTV (either 700mg/100mg twice a day [BID] or 1400mg/200mg QD)
Overall Number of Participants Analyzed 142 67
Measure Type: Number
Unit of Measure: participants
Any event 2 0
Alanine aminotransferase increased 1 0
Aspartate aminotransferase increased 1 0
Metastatic neoplasms 1 0
Central nervous system lesion 1 0
7.Secondary Outcome
Title Number of Participants With Grade 2-4 Adverse Events Occurring in Greater Than or Equal to 2% of Subjects Through Week 24
Hide Description The number of participants who experienced any grades 2 to 4 adverse events was tabulated. Adverse events were graded based on the Division of Acquired Immunodeficiency Syndrome (AIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events.
Time Frame Baseline through Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population
Arm/Group Title FPV/r100 FPV/r200
Hide Arm/Group Description:
Fosamprenavir (FPV)/ritonavir (RTV) 1400mg/100mg once a day (QD)
FPV/RTV (either 700mg/100mg twice a day [BID] or 1400mg/200mg QD)
Overall Number of Participants Analyzed 142 67
Measure Type: Number
Unit of Measure: participants
Any event 48 24
Diarrhea 8 2
Bronchitis 3 3
Nausea 3 1
Sinusitis 3 1
Upper respiratory tract infection 4 0
Blood glucose increased 3 0
Depression 1 2
Headache 1 2
Influenza 1 2
Low density lipoprotein increased 3 0
Nasopharyngitis 3 0
Otitis media 1 2
Back pain 0 2
Hypercholesterolemia 0 2
Insomnia 0 2
8.Secondary Outcome
Title Percent Change From Baseline in Total Cholesterol, High Density Lipoprotein (HDL), and Triglycerides at Week 24
Hide Description A blood sample was drawn to determine the cholesterol, HDL, triglycerides levels at Week 24. Percent change in total blood cholesterol, HDL, and triglycerides was defined as (lipid level at Week 24 minus level at baseline) divided by level at baseline x 100%.
Time Frame Baseline and Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population
Arm/Group Title FPV/r100 FPV/r200
Hide Arm/Group Description:
Fosamprenavir (FPV)/ritonavir (RTV) 1400mg/100mg once a day (QD)
FPV/RTV (either 700mg/100mg twice a day [BID] or 1400mg/200mg QD)
Overall Number of Participants Analyzed 123 60
Median (Full Range)
Unit of Measure: Percent change
Total cholesterol
-0.5
(-41.8 to 31.3)
0.7
(-35.4 to 91)
HDL
-2.1
(-34.8 to 47.4)
0
(-34.1 to 31.7)
Triglycerides
-13.5
(-87.7 to 169.2)
-0.6
(-52.2 to 191.1)
9.Secondary Outcome
Title Percent Change From Baseline in Low Density Lipoprotein (LDL) at Week 24
Hide Description A blood sample was drawn to determine the LDL level at Week 24. Percent change in LDL was defined as (LDL level at Week 24 minus level at baseline) divided by level at baseline x 100%.
Time Frame Baseline and Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population
Arm/Group Title FPV/r100 FPV/r200
Hide Arm/Group Description:
Fosamprenavir (FPV)/ritonavir (RTV) 1400mg/100mg once a day (QD)
FPV/RTV (either 700mg/100mg twice a day [BID] or 1400mg/200mg QD)
Overall Number of Participants Analyzed 115 56
Median (Full Range)
Unit of Measure: Percent change
0
(-47 to 103.8)
2.1
(-60.5 to 142.2)
10.Secondary Outcome
Title Number of Participants With Plasma HIV-1 RNA Genotypic Mutations and Phenotypic Resistance at Time of Virologic Failure Not Present at Baseline
Hide Description A blood sample was drawn for subjects failing to respond to therapy and the mutations present in the virus were identified. For each subject, 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.
Time Frame Baseline through Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the ITT-E Population who met the virologic failure definition
Arm/Group Title FPV/r100 FPV/r200
Hide Arm/Group Description:
Fosamprenavir (FPV)/ritonavir (RTV) 1400mg/100mg once a day (QD)
FPV/RTV (either 700mg/100mg twice a day [BID] or 1400mg/200mg QD)
Overall Number of Participants Analyzed 0 1
Measure Type: Number
Unit of Measure: Participants
0
11.Secondary Outcome
Title Steady-State Plasma Levels of Amprenavir (APV) and Ritonavir (RTV) Ctau at Weeks 12 and 24
Hide Description Blood samples were drawn at weeks 12 and 24 to determine the plasma levels of APV and RTV. Concentration at the end of the dosing interval at steady state (Ctau) was presented.
Time Frame Weeks 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 or RTV Ctau data.
Arm/Group Title FPV/r100 FPV/r200 FPV/RTV 700/100 mg BID
Hide Arm/Group Description:
Fosamprenavir (FPV)/ritonavir (RTV) 1400/100mg once a day (QD)
FPV/RTV (either 700/100mg twice a day [BID] or 1400/200mg QD)
Twice daily FPV regimen boosted with a reduced dose of RTV 100 mg
Overall Number of Participants Analyzed 61 17 17
Geometric Mean (95% Confidence Interval)
Unit of Measure: micrograms/mL
Week 12 APV Ctau
1.38
(1.09 to 1.74)
1.28
(0.69 to 2.37)
1.35
(0.44 to 4.11)
Week 24 APV Ctau
1.27
(0.99 to 1.62)
1.49
(1.02 to 2.18)
2.38
(1.68 to 3.37)
Week 12 RTV Ctau
0.026
(0 to 0.286)
0.050
(0 to 0.346)
0.228
(0 to 0.568)
Week 24 RTV Ctau
0.022
(0 to 2.49)
0.056
(0 to 0.634)
0.203
(0 to 1.10)
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title FPV/r100 FPV/r200
Hide Arm/Group Description Fosamprenavir (FPV)/ritonavir (RTV) 1400mg/100mg once a day (QD) FPV/RTV (either 700mg/100mg twice a day [BID] or 1400mg/200mg QD)
All-Cause Mortality
FPV/r100 FPV/r200
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
FPV/r100 FPV/r200
Affected / at Risk (%) Affected / at Risk (%)
Total   7   1 
Cardiac disorders     
Cardiac failure congestive  1  1/142 (0.70%)  0/67 (0.00%) 
Gastrointestinal disorders     
Pancreatitis chronic  1  1/142 (0.70%)  0/67 (0.00%) 
Peptic ulcer  1  1/142 (0.70%)  0/67 (0.00%) 
General disorders     
Chest pain  1  0/142 (0.00%)  1/67 (1.49%) 
Infections and infestations     
Appendicitis  1  1/142 (0.70%)  0/67 (0.00%) 
Cellulitis  1  1/142 (0.70%)  0/67 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Metastatic neoplasm  1  1/142 (0.70%)  0/67 (0.00%) 
Nervous system disorders     
Central nervous system lesion  2  1/142 (0.70%)  0/67 (0.00%) 
Cerebrovascular accident  1  1/142 (0.70%)  0/67 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA
2
Term from vocabulary, MeDRA
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
FPV/r100 FPV/r200
Affected / at Risk (%) Affected / at Risk (%)
Total   18   6 
Gastrointestinal disorders     
Diarrhea  1  9/142 (6.34%)  4/67 (5.97%) 
Infections and infestations     
Upper respiratory tract infection  1  10/142 (7.04%)  2/67 (2.99%) 
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
Name/Title: GSK Response Center
Organization: GlaxoSmithKline
Phone: 866-435-7343
Responsible Party: E.D. Derilus; Clinical Disclosure Advisor, GSK Clinical Disclosure
ClinicalTrials.gov Identifier: NCT00363142     History of Changes
Other Study ID Numbers: LEX106430
First Submitted: August 11, 2006
First Posted: August 15, 2006
Results First Submitted: June 11, 2009
Results First Posted: September 24, 2009
Last Update Posted: November 5, 2010