Trial Outcomes & Findings for A Study of an Investigational Regimen Combining FDA Approved HIV Drugs in HIV-Infected Subjects (NCT NCT00363142)

NCT ID: NCT00363142

Last Updated: 2010-11-05

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

211 participants

Primary outcome timeframe

Week 24

Results posted on

2010-11-05

Participant Flow

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.

Participant milestones

Participant milestones
Measure
FPV/r100
Fosamprenavir (FPV)/ritonavir (RTV) 1400mg/100mg once a day (QD)
FPV/r200
FPV/RTV (either 700mg/100mg twice a day \[BID\] or 1400mg/200mg QD)
Overall Study
STARTED
140
69
Overall Study
COMPLETED
133
66
Overall Study
NOT COMPLETED
7
3

Reasons for withdrawal

Reasons for withdrawal
Measure
FPV/r100
Fosamprenavir (FPV)/ritonavir (RTV) 1400mg/100mg once a day (QD)
FPV/r200
FPV/RTV (either 700mg/100mg twice a day \[BID\] or 1400mg/200mg QD)
Overall Study
Adverse Event
2
0
Overall Study
Lack of Efficacy
0
1
Overall Study
Lost to Follow-up
1
0
Overall Study
Non-compliance
1
1
Overall Study
Withdrawal by Subject
3
1

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
FPV/r100
n=140 Participants
Fosamprenavir (FPV)/ritonavir (RTV) 1400mg/100mg once a day (QD)
FPV/r200
n=69 Participants
FPV/RTV (either 700mg/100mg twice a day \[BID\] or 1400mg/200mg QD)
Total
n=209 Participants
Total of all reporting groups
Age Continuous
44.9 years
STANDARD_DEVIATION 10.52 • n=5 Participants
44.3 years
STANDARD_DEVIATION 8.9 • n=7 Participants
44.7 years
STANDARD_DEVIATION 10.00 • n=5 Participants
Sex: Female, Male
Female
33 Participants
n=5 Participants
9 Participants
n=7 Participants
42 Participants
n=5 Participants
Sex: Female, Male
Male
107 Participants
n=5 Participants
60 Participants
n=7 Participants
167 Participants
n=5 Participants
Race/Ethnicity, Customized
African American/African heritage
42 participants
n=5 Participants
20 participants
n=7 Participants
62 participants
n=5 Participants
Race/Ethnicity, Customized
American Indian/Alaskan native
1 participants
n=5 Participants
0 participants
n=7 Participants
1 participants
n=5 Participants
Race/Ethnicity, Customized
Asian - South East Asian
0 participants
n=5 Participants
2 participants
n=7 Participants
2 participants
n=5 Participants
Race/Ethnicity, Customized
Native Hawaiian or Other Pacific Islander
0 participants
n=5 Participants
1 participants
n=7 Participants
1 participants
n=5 Participants
Race/Ethnicity, Customized
White - Arabic/North African
0 participants
n=5 Participants
2 participants
n=7 Participants
2 participants
n=5 Participants
Race/Ethnicity, Customized
White - White/Caucasian/European
95 participants
n=5 Participants
44 participants
n=7 Participants
139 participants
n=5 Participants
Race/Ethnicity, Customized
Mixed race
1 participants
n=5 Participants
0 participants
n=7 Participants
1 participants
n=5 Participants
Race/Ethnicity, Customized
Other
1 participants
n=5 Participants
0 participants
n=7 Participants
1 participants
n=5 Participants
Ethnicity (NIH/OMB)
Hispanic or Latino
31 Participants
n=5 Participants
11 Participants
n=7 Participants
42 Participants
n=5 Participants
Ethnicity (NIH/OMB)
Not Hispanic or Latino
109 Participants
n=5 Participants
58 Participants
n=7 Participants
167 Participants
n=5 Participants
Ethnicity (NIH/OMB)
Unknown or Not Reported
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants

PRIMARY outcome

Timeframe: Week 24

Population: Intent-to-Treat Exposed (ITT-E) Population. Subjects who received at least one dose of investigational product.

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.

Outcome measures

Outcome measures
Measure
FPV/r100
n=140 Participants
Fosamprenavir (FPV)/ritonavir (RTV) 1400mg/100mg once a day (QD)
FPV/r200
n=69 Participants
FPV/RTV (either 700mg/100mg twice a day \[BID\] or 1400mg/200mg QD)
FPV/RTV 700/100 mg BID
Twice daily FPV regimen boosted with a reduced dose of RTV 100 mg
Percentage of Participants Not Meeting the Definition of Virologic Failure at or Prior to Week 24
92.1 Percentage of participants
94.2 Percentage of participants

SECONDARY outcome

Timeframe: Week 24

Population: ITT-E Population

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.

Outcome measures

Outcome measures
Measure
FPV/r100
n=140 Participants
Fosamprenavir (FPV)/ritonavir (RTV) 1400mg/100mg once a day (QD)
FPV/r200
n=69 Participants
FPV/RTV (either 700mg/100mg twice a day \[BID\] or 1400mg/200mg QD)
FPV/RTV 700/100 mg BID
Twice daily FPV regimen boosted with a reduced dose of RTV 100 mg
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
Plasma HIV-1 RNA <400 copies/mL
92 Percentage of participants
94.2 Percentage of participants
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
HIV-1 RNA greater than or equal to 400 copies/mL
8 Percentage of participants
5.8 Percentage of participants

SECONDARY outcome

Timeframe: Week 24

Population: ITT-E Population

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.

Outcome measures

Outcome measures
Measure
FPV/r100
n=140 Participants
Fosamprenavir (FPV)/ritonavir (RTV) 1400mg/100mg once a day (QD)
FPV/r200
n=69 Participants
FPV/RTV (either 700mg/100mg twice a day \[BID\] or 1400mg/200mg QD)
FPV/RTV 700/100 mg BID
Twice daily FPV regimen boosted with a reduced dose of RTV 100 mg
Percentage of Participants With Plasma HIV-1 RNA <50 Copies/mL at Week 24, TLOVR Analysis
Plasma HIV-1 RNA <50 copies/mL
82.9 Percentage of participants
84.6 Percentage of participants
Percentage of Participants With Plasma HIV-1 RNA <50 Copies/mL at Week 24, TLOVR Analysis
HIV-1 RNA greater than or equal to 50 copies/mL
17.1 Percentage of participants
15.4 Percentage of participants

SECONDARY outcome

Timeframe: Baseline and Week 24

Population: ITT-E Population - Observed Analysis, available data from those subjects who had values at baseline and at Week 24

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.

Outcome measures

Outcome measures
Measure
FPV/r100
n=131 Participants
Fosamprenavir (FPV)/ritonavir (RTV) 1400mg/100mg once a day (QD)
FPV/r200
n=66 Participants
FPV/RTV (either 700mg/100mg twice a day \[BID\] or 1400mg/200mg QD)
FPV/RTV 700/100 mg BID
Twice daily FPV regimen boosted with a reduced dose of RTV 100 mg
Mean Change From Baseline of log10 Copies/mL Plasma HIV-1 RNA Levels at Week 24, Observed Analysis
-0.015 log10 copies/mL
Standard Deviation 0.388
-0.022 log10 copies/mL
Standard Deviation 0.130

SECONDARY outcome

Timeframe: Baseline and Week 24

Population: ITT-E Population - Observed Analysis, available data from those subjects who had values at baseline and at Week 24

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.

Outcome measures

Outcome measures
Measure
FPV/r100
n=132 Participants
Fosamprenavir (FPV)/ritonavir (RTV) 1400mg/100mg once a day (QD)
FPV/r200
n=67 Participants
FPV/RTV (either 700mg/100mg twice a day \[BID\] or 1400mg/200mg QD)
FPV/RTV 700/100 mg BID
Twice daily FPV regimen boosted with a reduced dose of RTV 100 mg
Median Change From Baseline of CD4+ Cell Count at Week 24, Observed Analysis
11.5 cells/mm3
Full Range 0.073 • Interval -386.0 to 407.0
15 cells/mm3
Full Range 0.194 • Interval -201.0 to 454.0

SECONDARY outcome

Timeframe: Baseline through Week 24

Population: Safety Population: all randomized subjects who consumed at least one dose of study drug and was analyzed according to the treatment received.

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.

Outcome measures

Outcome measures
Measure
FPV/r100
n=142 Participants
Fosamprenavir (FPV)/ritonavir (RTV) 1400mg/100mg once a day (QD)
FPV/r200
n=67 Participants
FPV/RTV (either 700mg/100mg twice a day \[BID\] or 1400mg/200mg QD)
FPV/RTV 700/100 mg BID
Twice daily FPV regimen boosted with a reduced dose of RTV 100 mg
Number of Participants Who Discontinued Treatment Due to Adverse Events Through Week 24
Any event
2 participants
0 participants
Number of Participants Who Discontinued Treatment Due to Adverse Events Through Week 24
Alanine aminotransferase increased
1 participants
0 participants
Number of Participants Who Discontinued Treatment Due to Adverse Events Through Week 24
Aspartate aminotransferase increased
1 participants
0 participants
Number of Participants Who Discontinued Treatment Due to Adverse Events Through Week 24
Metastatic neoplasms
1 participants
0 participants
Number of Participants Who Discontinued Treatment Due to Adverse Events Through Week 24
Central nervous system lesion
1 participants
0 participants

SECONDARY outcome

Timeframe: Baseline through Week 24

Population: Safety Population

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.

Outcome measures

Outcome measures
Measure
FPV/r100
n=142 Participants
Fosamprenavir (FPV)/ritonavir (RTV) 1400mg/100mg once a day (QD)
FPV/r200
n=67 Participants
FPV/RTV (either 700mg/100mg twice a day \[BID\] or 1400mg/200mg QD)
FPV/RTV 700/100 mg BID
Twice daily FPV regimen boosted with a reduced dose of RTV 100 mg
Number of Participants With Grade 2-4 Adverse Events Occurring in Greater Than or Equal to 2% of Subjects Through Week 24
Insomnia
0 participants
2 participants
Number of Participants With Grade 2-4 Adverse Events Occurring in Greater Than or Equal to 2% of Subjects Through Week 24
Nausea
3 participants
1 participants
Number of Participants With Grade 2-4 Adverse Events Occurring in Greater Than or Equal to 2% of Subjects Through Week 24
Any event
48 participants
24 participants
Number of Participants With Grade 2-4 Adverse Events Occurring in Greater Than or Equal to 2% of Subjects Through Week 24
Diarrhea
8 participants
2 participants
Number of Participants With Grade 2-4 Adverse Events Occurring in Greater Than or Equal to 2% of Subjects Through Week 24
Bronchitis
3 participants
3 participants
Number of Participants With Grade 2-4 Adverse Events Occurring in Greater Than or Equal to 2% of Subjects Through Week 24
Sinusitis
3 participants
1 participants
Number of Participants With Grade 2-4 Adverse Events Occurring in Greater Than or Equal to 2% of Subjects Through Week 24
Upper respiratory tract infection
4 participants
0 participants
Number of Participants With Grade 2-4 Adverse Events Occurring in Greater Than or Equal to 2% of Subjects Through Week 24
Blood glucose increased
3 participants
0 participants
Number of Participants With Grade 2-4 Adverse Events Occurring in Greater Than or Equal to 2% of Subjects Through Week 24
Depression
1 participants
2 participants
Number of Participants With Grade 2-4 Adverse Events Occurring in Greater Than or Equal to 2% of Subjects Through Week 24
Headache
1 participants
2 participants
Number of Participants With Grade 2-4 Adverse Events Occurring in Greater Than or Equal to 2% of Subjects Through Week 24
Influenza
1 participants
2 participants
Number of Participants With Grade 2-4 Adverse Events Occurring in Greater Than or Equal to 2% of Subjects Through Week 24
Low density lipoprotein increased
3 participants
0 participants
Number of Participants With Grade 2-4 Adverse Events Occurring in Greater Than or Equal to 2% of Subjects Through Week 24
Nasopharyngitis
3 participants
0 participants
Number of Participants With Grade 2-4 Adverse Events Occurring in Greater Than or Equal to 2% of Subjects Through Week 24
Otitis media
1 participants
2 participants
Number of Participants With Grade 2-4 Adverse Events Occurring in Greater Than or Equal to 2% of Subjects Through Week 24
Back pain
0 participants
2 participants
Number of Participants With Grade 2-4 Adverse Events Occurring in Greater Than or Equal to 2% of Subjects Through Week 24
Hypercholesterolemia
0 participants
2 participants

SECONDARY outcome

Timeframe: Baseline and Week 24

Population: Safety Population

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%.

Outcome measures

Outcome measures
Measure
FPV/r100
n=123 Participants
Fosamprenavir (FPV)/ritonavir (RTV) 1400mg/100mg once a day (QD)
FPV/r200
n=60 Participants
FPV/RTV (either 700mg/100mg twice a day \[BID\] or 1400mg/200mg QD)
FPV/RTV 700/100 mg BID
Twice daily FPV regimen boosted with a reduced dose of RTV 100 mg
Percent Change From Baseline in Total Cholesterol, High Density Lipoprotein (HDL), and Triglycerides at Week 24
Total cholesterol
-0.5 Percent change
Interval -41.8 to 31.3
0.7 Percent change
Interval -35.4 to 91.0
Percent Change From Baseline in Total Cholesterol, High Density Lipoprotein (HDL), and Triglycerides at Week 24
HDL
-2.1 Percent change
Interval -34.8 to 47.4
0 Percent change
Interval -34.1 to 31.7
Percent Change From Baseline in Total Cholesterol, High Density Lipoprotein (HDL), and Triglycerides at Week 24
Triglycerides
-13.5 Percent change
Interval -87.7 to 169.2
-0.6 Percent change
Interval -52.2 to 191.1

SECONDARY outcome

Timeframe: Baseline and Week 24

Population: Safety Population

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%.

Outcome measures

Outcome measures
Measure
FPV/r100
n=115 Participants
Fosamprenavir (FPV)/ritonavir (RTV) 1400mg/100mg once a day (QD)
FPV/r200
n=56 Participants
FPV/RTV (either 700mg/100mg twice a day \[BID\] or 1400mg/200mg QD)
FPV/RTV 700/100 mg BID
Twice daily FPV regimen boosted with a reduced dose of RTV 100 mg
Percent Change From Baseline in Low Density Lipoprotein (LDL) at Week 24
0 Percent change
Interval -47.0 to 103.8
2.1 Percent change
Interval -60.5 to 142.2

SECONDARY outcome

Timeframe: Baseline through Week 24

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

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.

Outcome measures

Outcome measures
Measure
FPV/r100
Fosamprenavir (FPV)/ritonavir (RTV) 1400mg/100mg once a day (QD)
FPV/r200
n=1 Participants
FPV/RTV (either 700mg/100mg twice a day \[BID\] or 1400mg/200mg QD)
FPV/RTV 700/100 mg BID
Twice daily FPV regimen boosted with a reduced dose of RTV 100 mg
Number of Participants With Plasma HIV-1 RNA Genotypic Mutations and Phenotypic Resistance at Time of Virologic Failure Not Present at Baseline
0 Participants

SECONDARY outcome

Timeframe: Weeks 12 and 24

Population: PK Parameter (Ctau) Population - Participants in the ITT-E Population who underwent PK sampling and had evaluable APV or RTV Ctau data.

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.

Outcome measures

Outcome measures
Measure
FPV/r100
n=61 Participants
Fosamprenavir (FPV)/ritonavir (RTV) 1400mg/100mg once a day (QD)
FPV/r200
n=17 Participants
FPV/RTV (either 700mg/100mg twice a day \[BID\] or 1400mg/200mg QD)
FPV/RTV 700/100 mg BID
n=17 Participants
Twice daily FPV regimen boosted with a reduced dose of RTV 100 mg
Steady-State Plasma Levels of Amprenavir (APV) and Ritonavir (RTV) Ctau at Weeks 12 and 24
Week 12 APV Ctau
1.38 micrograms/mL
Interval 1.09 to 1.74
1.28 micrograms/mL
Interval 0.69 to 2.37
1.35 micrograms/mL
Interval 0.44 to 4.11
Steady-State Plasma Levels of Amprenavir (APV) and Ritonavir (RTV) Ctau at Weeks 12 and 24
Week 12 RTV Ctau
0.026 micrograms/mL
Interval 0.0 to 0.286
0.050 micrograms/mL
Interval 0.0 to 0.346
0.228 micrograms/mL
Interval 0.0 to 0.568
Steady-State Plasma Levels of Amprenavir (APV) and Ritonavir (RTV) Ctau at Weeks 12 and 24
Week 24 APV Ctau
1.27 micrograms/mL
Interval 0.99 to 1.62
1.49 micrograms/mL
Interval 1.02 to 2.18
2.38 micrograms/mL
Interval 1.68 to 3.37
Steady-State Plasma Levels of Amprenavir (APV) and Ritonavir (RTV) Ctau at Weeks 12 and 24
Week 24 RTV Ctau
0.022 micrograms/mL
Interval 0.0 to 2.49
0.056 micrograms/mL
Interval 0.0 to 0.634
0.203 micrograms/mL
Interval 0.0 to 1.1

Adverse Events

FPV/r100

Serious events: 7 serious events
Other events: 18 other events
Deaths: 0 deaths

FPV/r200

Serious events: 1 serious events
Other events: 6 other events
Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure
FPV/r100
Fosamprenavir (FPV)/ritonavir (RTV) 1400mg/100mg once a day (QD)
FPV/r200
FPV/RTV (either 700mg/100mg twice a day \[BID\] or 1400mg/200mg QD)
Gastrointestinal disorders
Pancreatitis chronic
0.70%
1/142
0.00%
0/67
Gastrointestinal disorders
Peptic ulcer
0.70%
1/142
0.00%
0/67
Infections and infestations
Appendicitis
0.70%
1/142
0.00%
0/67
Infections and infestations
Cellulitis
0.70%
1/142
0.00%
0/67
Nervous system disorders
Central nervous system lesion
0.70%
1/142
0.00%
0/67
Nervous system disorders
Cerebrovascular accident
0.70%
1/142
0.00%
0/67
Cardiac disorders
Cardiac failure congestive
0.70%
1/142
0.00%
0/67
General disorders
Chest pain
0.00%
0/142
1.5%
1/67
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastatic neoplasm
0.70%
1/142
0.00%
0/67

Other adverse events

Other adverse events
Measure
FPV/r100
Fosamprenavir (FPV)/ritonavir (RTV) 1400mg/100mg once a day (QD)
FPV/r200
FPV/RTV (either 700mg/100mg twice a day \[BID\] or 1400mg/200mg QD)
Gastrointestinal disorders
Diarrhea
6.3%
9/142
6.0%
4/67
Infections and infestations
Upper respiratory tract infection
7.0%
10/142
3.0%
2/67

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