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An Interaction Study to Assess Drug Levels in Fasting Healthy Adult Subjects

A Randomized, Open-Label, Six-Period, Drug Interaction Study to Assess Steady-State Plasma Amprenavir (APV) and Raltegravir (RTG) Pharmacokinetics Following Administration of RTG 400 mg BID for 14 Days Alone and in Combination With 14 Days of Either Fosamprenavir (FPV) 1400 mg BID, FPV 700 mg BID + RTV 100 mg BID or FPV 1400 mg + RTV 100 mg QD in Healthy Adult Subjects When Under Fasting Conditions

Status
Completed
Phases
NA
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT00802074
Enrollment
45
Registered
2008-12-04
Start date
2008-12-31
Completion date
2009-04-30
Last updated
2016-01-29

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Healthy

Keywords

Healthy Subjects, Pharmacokinetics study, Pharmacokinetics of medications

Brief summary

To date, no study has investigated whether there is a drug interaction between the protease inhibitor fosamprenavir and the integrase inhibitor raltegravir. COL112775 is a randomized, open-label, 6-arm, 3-period, drug interaction study to assess steady-state plasma amprenavir (APV) and raltegravir (RTG) pharmacokinetics in 48 healthy, fasting, HIV-negative adults after administration of a 7-day regimen of RTG 400mg BID alone and after 14-day regimens of unboosted fosamprenavir (FPV) 1400mg twice daily (BID), FPV 700mg/RTV 100mg BID, or FPV 1400mg/ritonavir (RTV) 100mg once daily (QD) with and without concurrent RTG 400mg BID. Blood samples for drug concentration measurement will be collected over 12 hours at the end of each dosing period. Subjects will undergo a physical examination, complete blood count (CBC) with differential, HIV test, hepatitis B/C test, liver function test, renal function analysis, and lipid panel at screening, and all of these tests, except those for HIV and hepatitis B/C, will be repeated at follow-up post-study. Adverse events and adherence (by pill count and medication diary) will be assessed by the investigator/study personnel at the end of each dosing period

Detailed description

This randomized, open-label, six-arm, three-period drug interaction study will recruit 48 healthy volunteers so as to obtain a minimum of 36 evaluable subjects at a single study center in the U.S. The study will have a screening visit, 3 treatment visits for pharmacokinetics (PK) sampling and a follow-up visit. The screening visit will be conducted within 30 days prior to receiving the first dose. Subjects will then be randomized into 1 of 6 treatment groups as shown below: Cohort Size Period 1 Period 2 Period 3 Sample Days 1 to 7 Days 1-14 Days 1-14 A 8 RTG 400mg BID, FPV 1400mg BID, FPV 1400mg BID + RTG 400mg BID B 8 RTG 400mg BID, FPV 1400mg BID + RTG 400mg BID , FPV 1400mg BID C 8 RTG 400mg BID, FPV 700mg BID + RTV 100mg BID, FPV 700mg BID + RTV 100mg BID + RTG 400mg BID D 8 RTG 400mg BID, FPV 700mg BID + RTV 100mg BID + RTG 400mg BID, FPV 700mg BID + RTV 100mg BID E 8 RTG 400mg BID, FPV 1400mg QD + RTV 100mg QD, FPV 1400mg QD + RTV 100mg QD + RTG 400mg BID F 8 RTG 400mg BID, FPV 1400mg QD + RTV 100mg QD + RTG 400mg BID, FPV 1400mg QD + RTV 100mg QD Study subjects will enter the clinic in the morning prior to dosing in a fasting state and remain at the center for 12 hours following each dose. Fourteen to 21 days following completion of the third dosing period, study subjects will return to the clinic for follow-up assessment. The total duration of the study will be approximately 86 days from screening through follow up. Blood samples for drug concentration measurement of amprenavir (APV) and raltegravir (RTG) concentrations will be collected over 12 hours at the end of each dosing period (at 0 \[baseline\], 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours post-dose). Subjects will undergo a physical examination, CBC with differential, HIV test, hepatitis B/C test, liver function test, renal function analysis, and lipid panel at screening, and all of these tests except those for HIV and hepatitis B/C will be repeated at follow-up post-study. Adverse events and adherence (by pill count and medication diary) will be assessed by the investigator/study personnel at the end of each dosing period. Evaluable patients will be required to have adhered to at least 95% of their study drug doses. Plasma APV concentrations will be analyzed using a validated high-performance liquid chromatography method with tandem mass spectrometric detection (HPLC/MS/MS) and plasma RTG concentrations by triple quadruple mass spectrometry. Plasma APV and RTG pharmacokinetic parameters measured will include maximum concentration (Cmax), time to maximum concentration (Tmax), minimum concentration (Cmin), and area under the concentration-time curve (AUC). All these parameters, except Tmax, will be log-transformed before statistical analysis. Analysis of variance, considering treatment as a fixed effect and subject as a random effect will be performed using Statistical Analysis Software (SAS), and assuming a treatment ratio for steady-state APV PK parameters as 1.0, the 90% confidence intervals will be within the range 0.81-1.24

Interventions

DRUGRaltegravir

400mg BID

DRUGFosamprenavir

1400mg BID, 700 mg BID or 1400 mg QD

DRUGRitonavir

100 mg BID or QD

Sponsors

GlaxoSmithKline
CollaboratorINDUSTRY
Garden State Infectious Disease Associates, PA
Lead SponsorOTHER

Study design

Allocation
RANDOMIZED
Intervention model
FACTORIAL
Masking
NONE

Eligibility

Sex/Gender
ALL
Age
18 Years to 64 Years
Healthy volunteers
Yes

Inclusion criteria

* Healthy subjects with no clinically significant abnormality identified by physician by evaluation of medical history, physical examination, clinical laboratory tests or vital signs. * Between 18 and 64 years. * A female subject is eligible to participate if she is neither pregnant nor lactating, and falls into one of the following categories: * non-childbearing potential including females with documented (medical report verification) hysterectomy or bilateral oophorectomy, or post-menopausal females defined as being amenorrheic for greater than 1 year and having estradiol and follicle stimulating hormone (FSH) levels consistent with menopause. * childbearing potential with a negative serum pregnancy test at screen and who agrees to use one of the following methods of contraception from screening or at least two weeks prior to the first dose (whichever is earlier) until the follow-up visit (any contraception method must be used consistently and correctly, i.e., in accordance with both the product label and the instructions of a physician). * Agreement for complete abstinence from intercourse. * Double barrier contraception (male condom/spermicide, male condom/diaphragm, diaphragm/spermicide). * Any intrauterine device (IUD) with published data showing that the expected failure rate is less than 1% per year (not all IUDs meet this criterion) * Any other method with published data showing that the lowest expected failure rate for that method is less than 1% per year. * Adequate renal function (calculated creatinine clearance via Cockcroft and Gault method (CrCl) \> 50 mL/min). * Adequate hepatic function (total bilirubin \< 2.5mg/dL; hepatic transaminases \< 5x normal). * Adequate hematologic function (absolute neutrophil count \[ANC\] \> 750 neutrophils/mm\^3; platelets \> 50,000/mm\^3; hematocrit \> 25%). * Non-smoker, defined as not having used nicotine-containing products within the past 6 months. * Willingness and ability to adhere to treatment and follow-up procedures. * The ability to understand and sign a written informed consent form. * Body weight \> or =50 kg for males and \> or=45 kg for females and body mass index (BMI) in the range of 19 to 30 kg/m\^2 (BMI = weight \[kg\]/(height \[m\])\^2).

Exclusion criteria

* Have an active infection that required parenteral antibiotics or hospitalization within 2 weeks prior to enrollment. * A history of or documented gastrointestinal diseases that impact drug absorption. * Have a significant documented sulfa allergy (e.g., Stevens-Johnson Syndrome) or a history of sensitivity to any of the study medications, or components thereof. * HIV, Hepatitis B or C positive . * Cigarette/cigar/pipe smokers. * History of alcohol/drug abuse or dependence within 12 months of the study, or a history of alcohol consumption in the past six months exceeding 7 units/week for women and 14 units/week for men (where 1 unit = 5 ounces of wine or 12 ounces of beer or 1.5 ounces of hard liquor). * Treatment with an investigational drug within 30 days or 5 half-lives (whichever is longer) preceding the first dose of study medication. * Use of prescription or non-prescription drugs (including aspirin and nonsteroidal anti-inflammatory drug (NSAIDs), vitamins, herbal and dietary supplements within 7 days (or 14 days if the drug is a potential enzyme inducer, such as St. John's Wort) or 5 half-lives (whichever is longer) prior to the first dose of study medication, unless in the opinion of the investigator the medication will not interfere with the study procedures or compromise subject safety. * Subjects who have donated plasma within 7 days prior to the screening visit or where participation in this study would result in donation of blood in excess of 500 mL of blood within 56 day period.

Design outcomes

Primary

MeasureTime frameDescription
CL/F: Fasting Steady-state Plasma Amprenavir (APV) Pharmacokinetics (PK) Following Administration of Fosamprenavir (FPV) 1400mg BID, FPV 700mg/Ritonavir (RTV) 100 mg BID, or FPV 1400mg/RTV 100mg QD With and Without Concurrent Raltegravir (RTG) 400mg BID.Day 14 of the FPV 1400mg BID, FPV 1400mg/RAL 400mg BID, FPV 700mg/RTV 100mg BID, FPV 700mg/RTV 100mg/RAL 400mg BID, FPV 1400mg/RTV 100mg QD, and FPV 1400mg/RTV 100mg QD plus RAL 400mg BID regimensAmprenavir (APV) is the active ingredient/metabolite of Fosamprenavir (FPV). APV minimum concentration (Cmin), maximum concentration (Cmax), area under the plasma concentration-time curve (AUC), and oral clearance (CL/F) as determined from APV concentrations observed in blood samples obtained at baseline, and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours during the BID regimens (FPV 1400mg BID, FPV 700mg/RTV 100 mg BID), and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 24 hours during the QD regimen (FPV 1400mg/RTV 100mg QD). As Groups A and B received the same regimens (albeit in different order), PK data for these two groups were collated, then assessed. For the same reason, PK data from Groups C and D regimens were collated before assessment, as were the PK data from Groups E and F.
Cmin/Cmax: Fasting Steady-state Plasma Amprenavir (APV) Pharmacokinetics (PK) Following Admin of Fosamprenavir (FPV) 1400mg BID, FPV 700mg/Ritonavir (RTV) 100 mg BID, or FPV 1400mg/RTV 100mg QD With and Without Concurrent Raltegravir (RTG) 400mg BID.Day 14 of the FPV 1400mg BID, FPV 1400mg/RAL 400mg BID, FPV 700mg/RTV 100mg BID, FPV 700mg/RTV 100mg/RAL 400mg BID, FPV 1400mg/RTV 100mg QD, and FPV 1400mg/RTV 100mg QD plus RAL 400mg BID regimensAmprenavir (APV) is the active ingredient/metabolite of Fosamprenavir (FPV). APV minimum concentration (Cmin), maximum concentration (Cmax), area under the plasma concentration-time curve (AUC), and oral clearance (CL/F) as determined from APV concentrations observed in blood samples obtained at baseline, and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours during the BID regimens (FPV 1400mg BID, FPV 700mg/RTV 100 mg BID), and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 24 hours during the QD regimen (FPV 1400mg/RTV 100mg QD). As Groups A and B received the same regimens (albeit in different order), PK data for these two groups were collated, then assessed. For the same reason, PK data from Groups C and D regimens were collated before assessment, as were the PK data from Groups E and F.
AUC: Fasting Steady-state Plasma Amprenavir (APV) Pharmacokinetics (PK) Following Administration of Fosamprenavir (FPV) 1400mg BID, FPV 700mg/Ritonavir (RTV) 100 mg BID, or FPV 1400mg/RTV 100mg QD With and Without Concurrent Raltegravir (RTG) 400mg BID.Day 14 of the FPV 1400mg BID, FPV 1400mg/RAL 400mg BID, FPV 700mg/RTV 100mg BID, FPV 700mg/RTV 100mg/RAL 400mg BID, FPV 1400mg/RTV 100mg QD, and FPV 1400mg/RTV 100mg QD plus RAL 400mg BID regimensAmprenavir (APV) is the active ingredient/metabolite of Fosamprenavir (FPV). APV minimum concentration (Cmin), maximum concentration (Cmax), area under the plasma concentration-time curve (AUC), and oral clearance (CL/F) as determined from APV concentrations observed in blood samples obtained at baseline, and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours during the BID regimens (FPV 1400mg BID, FPV 700mg/RTV 100 mg BID), and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 24 hours during the QD regimen (FPV 1400mg/RTV 100mg QD). As Groups A and B received the same regimens (albeit in different order), PK data for these two groups were collated, then assessed. For the same reason, PK data from Groups C and D regimens were collated before assessment, as were the PK data from Groups E and F.
CL/F: Steady-state Plasma RTG PK Following Administration of RTG 400mg BID Alone and Following Co-administration With FPV 1400mg BID, FPV 700mg/RTV 100 mg BID, or FPV 1400mg/RTV 100mg QDDay 7 of the RAL 400mg BID regimen and Day 14 of the RAL 400mg/FPV 1400mg BID, RAL 400mg/FPV 700mg/RTV 100mg BID, and RAL 400mg BID Plus FPV 1400mg/RTV 100mg QD regimensAmprenavir (APV) is the active ingredient/metabolite of Fosamprenavir (FPV). RAL minimum concentration (Cmin), maximum concentration (Cmax), area under the plasma concentration-time curve (AUC), and oral clearance (CL/F) as determined from RAL concentrations observed in blood samples obtained at baseline, and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours during the period when RAL 400mg BID was administered with the FPV-Containing BID regimens (FPV 1400mg BID, FPV 700mg/RTV 100 mg BID), and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 24 hours during the period when RAL 400mg BID was administered with the FPV QD regimen (FPV 1400mg/RTV 100mg QD). As Groups A and B received the same regimens (albeit in different order), PK data for these two groups were collated, then assessed. For the same reason, PK data from Groups C and D regimens were collated before assessment, as were the PK data from Groups E and F.
Cmin/Cmax: Steady-state Plasma RTG PK Following Admin of RTG 400mg BID Alone and Following Co-administration With FPV 1400mg BID, FPV 700mg/RTV 100 mg BID, or FPV 1400mg/RTV 100mg QDDay 7 of the RAL 400mg BID regimen and Day 14 of the RAL 400mg/FPV 1400mg BID, RAL 400mg/FPV 700mg/RTV 100mg BID, and RAL 400mg BID Plus FPV 1400mg/RTV 100mg QD regimensAmprenavir (APV) is the active ingredient/metabolite of Fosamprenavir (FPV). RAL minimum concentration (Cmin), maximum concentration (Cmax), area under the plasma concentration-time curve (AUC), and oral clearance (CL/F) as determined from RAL concentrations observed in blood samples obtained at baseline, and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours during the period when RAL 400mg BID was administered with the FPV-Containing BID regimens (FPV 1400mg BID, FPV 700mg/RTV 100 mg BID), and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 24 hours during the period when RAL 400mg BID was administered with the FPV QD regimen (FPV 1400mg/RTV 100mg QD). As Groups A and B received the same regimens (albeit in different order), PK data for these two groups were collated, then assessed. For the same reason, PK data from Groups C and D regimens were collated before assessment, as were the PK data from Groups E and F.
AUC: Steady-state Plasma RTG PK Following Administration of RTG 400mg BID Alone and Following Co-administration With FPV 1400mg BID, FPV 700mg/RTV 100 mg BID, or FPV 1400mg/RTV 100mg QDDay 7 of the RAL 400mg BID regimen and Day 14 of the RAL 400mg/FPV 1400mg BID, RAL 400mg/FPV 700mg/RTV 100mg BID, and RAL 400mg BID Plus FPV 1400mg/RTV 100mg QD regimensAmprenavir (APV) is the active ingredient/metabolite of Fosamprenavir (FPV). RAL minimum concentration (Cmin), maximum concentration (Cmax), area under the plasma concentration-time curve (AUC), and oral clearance (CL/F) as determined from RAL concentrations observed in blood samples obtained at baseline, and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours during the period when RAL 400mg BID was administered with the FPV-Containing BID regimens (FPV 1400mg BID, FPV 700mg/RTV 100 mg BID), and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 24 hours during the period when RAL 400mg BID was administered with the FPV QD regimen (FPV 1400mg/RTV 100mg QD). As Groups A and B received the same regimens (albeit in different order), PK data for these two groups were collated, then assessed. For the same reason, PK data from Groups C and D regimens were collated before assessment, as were the PK data from Groups E and F.

Secondary

MeasureTime frameDescription
Number of Participants Who Experienced Adverse EventsDay 0 through Day 49Safety/tolerability data included all adverse events (AEs) reported within the time frame of each regimen evaluated. The intent was to compare AE's for each sequence and not for each regimen. 3The regimens for which AE information was culled were: * RAL 400mg BID alone * FPV 1400mg BID alone * FPV 700mg/RTV 100 mg BID alone * FPV 1400mg/RTV 100mg QD alone * FPV 1400mg BID combined with RAL 400mg BID * FPV 700mg/RTV 100 mg BID combined with RAL 400mg BID * FPV 1400mg/RTV 100mg QD combined with RAL 400mg BID The severity of reported AEs was graded according to DAIDS criteria, Version 1.0 (National Institute of Allergy and Infectious Diseases (NIAID). Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 1.0. Division of Acquired Immunodeficiency Syndrome (DAIDS), Washington D.C.; 2004).

Countries

United States

Participant flow

Participants by arm

ArmCount
Group A
Period 1-Raltegravir 400mg BID Period 2- Fosamprenavir 1400mg BID Period 3- Fosamprenavir 1400mg BID + Raltegravir 400mg BID Raltegravir: 400mg BID Fosamprenavir: 1400mg BID, 700 mg BID or 1400 mg QD
7
Group B
Period 1-Raltegravir 400mg BID Period 2-Fosamprenavir 1400mg BID + Raltegravir 400mg BID Period 3 Fosamprenavir 1400mg BID Raltegravir: 400mg BID Fosamprenavir: 1400mg BID, 700 mg BID or 1400 mg QD
7
Group C
Period 1-Raltegravir 400mg BID Period2- Fosamprenavir 700mg BID + Ritonavir 100mg BID Period 3- Fosamprenavir 700mg BID + Ritonavir 100mg BID + Raltegravir 400mg BID Raltegravir: 400mg BID Fosamprenavir: 1400mg BID, 700 mg BID or 1400 mg QD
6
Group D
Period 1-Raltegravir 400mg BID Period 2- Fosamprenavir 700mg BID + Ritonavir 100mg BID + Raltegravir 400mg BID Period 3-Fosamprenavir 700mg BID + Ritonavir 100mg BID Raltegravir: 400mg BID Fosamprenavir: 1400mg BID, 700 mg BID or 1400 mg QD
7
Group E
Period 1-Raltegravir 400mg BID Period 2- Fosamprenavir 1400mg QD + Ritonavir 100mg QD Period 3- Fosamprenavir 1400mg QD + Ritonavir 100mg QD + Raltegravir 400mg BID Raltegravir: 400mg BID Fosamprenavir: 1400mg BID, 700 mg BID or 1400 mg QD
7
Group F
Period 1-Raltegravir 400mg BID Period 2-Fosamprenavir 1400mg QD + Ritonavir 100mg QD + Raltegravir 400mg BID Period 3-Fosamprenavir 1400mg QD + Ritonavir 100mg QD Raltegravir: 400mg BID Fosamprenavir: 1400mg BID, 700 mg BID or 1400 mg QD
7
Total41

Withdrawals & dropouts

PeriodReasonFG000FG001FG002FG003FG004FG005
Overall StudyAdverse Event111000
Overall StudyWithdrawal by Subject100000

Baseline characteristics

CharacteristicGroup AGroup BGroup CGroup DGroup EGroup FTotal
Age, Customized
18-25
4 participants4 participants3 participants3 participants3 participants3 participants20 participants
Age, Customized
26-33
2 participants0 participants2 participants1 participants4 participants3 participants12 participants
Age, Customized
34-41
0 participants2 participants1 participants1 participants0 participants0 participants4 participants
Age, Customized
42-49
1 participants0 participants0 participants1 participants0 participants0 participants2 participants
Age, Customized
50 and older
0 participants1 participants0 participants1 participants0 participants1 participants3 participants
Region of Enrollment
United States
7 participants7 participants6 participants7 participants7 participants7 participants41 participants
Sex: Female, Male
Female
3 Participants4 Participants2 Participants2 Participants3 Participants4 Participants18 Participants
Sex: Female, Male
Male
4 Participants3 Participants4 Participants5 Participants4 Participants3 Participants23 Participants

Adverse events

Event typeEG000
affected / at risk
EG001
affected / at risk
EG002
affected / at risk
EG003
affected / at risk
EG004
affected / at risk
EG005
affected / at risk
deaths
Total, all-cause mortality
— / —— / —— / —— / —— / —— / —
other
Total, other adverse events
3 / 73 / 74 / 64 / 75 / 75 / 7
serious
Total, serious adverse events
0 / 70 / 70 / 60 / 70 / 70 / 7

Outcome results

Primary

AUC: Fasting Steady-state Plasma Amprenavir (APV) Pharmacokinetics (PK) Following Administration of Fosamprenavir (FPV) 1400mg BID, FPV 700mg/Ritonavir (RTV) 100 mg BID, or FPV 1400mg/RTV 100mg QD With and Without Concurrent Raltegravir (RTG) 400mg BID.

Amprenavir (APV) is the active ingredient/metabolite of Fosamprenavir (FPV). APV minimum concentration (Cmin), maximum concentration (Cmax), area under the plasma concentration-time curve (AUC), and oral clearance (CL/F) as determined from APV concentrations observed in blood samples obtained at baseline, and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours during the BID regimens (FPV 1400mg BID, FPV 700mg/RTV 100 mg BID), and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 24 hours during the QD regimen (FPV 1400mg/RTV 100mg QD). As Groups A and B received the same regimens (albeit in different order), PK data for these two groups were collated, then assessed. For the same reason, PK data from Groups C and D regimens were collated before assessment, as were the PK data from Groups E and F.

Time frame: Day 14 of the FPV 1400mg BID, FPV 1400mg/RAL 400mg BID, FPV 700mg/RTV 100mg BID, FPV 700mg/RTV 100mg/RAL 400mg BID, FPV 1400mg/RTV 100mg QD, and FPV 1400mg/RTV 100mg QD plus RAL 400mg BID regimens

ArmMeasureValue (MEAN)
Group A & BAUC: Fasting Steady-state Plasma Amprenavir (APV) Pharmacokinetics (PK) Following Administration of Fosamprenavir (FPV) 1400mg BID, FPV 700mg/Ritonavir (RTV) 100 mg BID, or FPV 1400mg/RTV 100mg QD With and Without Concurrent Raltegravir (RTG) 400mg BID.0.64 ng•h/mL
Group C & DAUC: Fasting Steady-state Plasma Amprenavir (APV) Pharmacokinetics (PK) Following Administration of Fosamprenavir (FPV) 1400mg BID, FPV 700mg/Ritonavir (RTV) 100 mg BID, or FPV 1400mg/RTV 100mg QD With and Without Concurrent Raltegravir (RTG) 400mg BID.0.84 ng•h/mL
Group E & FAUC: Fasting Steady-state Plasma Amprenavir (APV) Pharmacokinetics (PK) Following Administration of Fosamprenavir (FPV) 1400mg BID, FPV 700mg/Ritonavir (RTV) 100 mg BID, or FPV 1400mg/RTV 100mg QD With and Without Concurrent Raltegravir (RTG) 400mg BID.0.76 ng•h/mL
Primary

AUC: Steady-state Plasma RTG PK Following Administration of RTG 400mg BID Alone and Following Co-administration With FPV 1400mg BID, FPV 700mg/RTV 100 mg BID, or FPV 1400mg/RTV 100mg QD

Amprenavir (APV) is the active ingredient/metabolite of Fosamprenavir (FPV). RAL minimum concentration (Cmin), maximum concentration (Cmax), area under the plasma concentration-time curve (AUC), and oral clearance (CL/F) as determined from RAL concentrations observed in blood samples obtained at baseline, and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours during the period when RAL 400mg BID was administered with the FPV-Containing BID regimens (FPV 1400mg BID, FPV 700mg/RTV 100 mg BID), and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 24 hours during the period when RAL 400mg BID was administered with the FPV QD regimen (FPV 1400mg/RTV 100mg QD). As Groups A and B received the same regimens (albeit in different order), PK data for these two groups were collated, then assessed. For the same reason, PK data from Groups C and D regimens were collated before assessment, as were the PK data from Groups E and F.

Time frame: Day 7 of the RAL 400mg BID regimen and Day 14 of the RAL 400mg/FPV 1400mg BID, RAL 400mg/FPV 700mg/RTV 100mg BID, and RAL 400mg BID Plus FPV 1400mg/RTV 100mg QD regimens

ArmMeasureValue (MEAN)
Group A & BAUC: Steady-state Plasma RTG PK Following Administration of RTG 400mg BID Alone and Following Co-administration With FPV 1400mg BID, FPV 700mg/RTV 100 mg BID, or FPV 1400mg/RTV 100mg QD0.63 ng*h/mL
Group C & DAUC: Steady-state Plasma RTG PK Following Administration of RTG 400mg BID Alone and Following Co-administration With FPV 1400mg BID, FPV 700mg/RTV 100 mg BID, or FPV 1400mg/RTV 100mg QD0.45 ng*h/mL
Group E & FAUC: Steady-state Plasma RTG PK Following Administration of RTG 400mg BID Alone and Following Co-administration With FPV 1400mg BID, FPV 700mg/RTV 100 mg BID, or FPV 1400mg/RTV 100mg QD0.85 ng*h/mL
Primary

CL/F: Fasting Steady-state Plasma Amprenavir (APV) Pharmacokinetics (PK) Following Administration of Fosamprenavir (FPV) 1400mg BID, FPV 700mg/Ritonavir (RTV) 100 mg BID, or FPV 1400mg/RTV 100mg QD With and Without Concurrent Raltegravir (RTG) 400mg BID.

Amprenavir (APV) is the active ingredient/metabolite of Fosamprenavir (FPV). APV minimum concentration (Cmin), maximum concentration (Cmax), area under the plasma concentration-time curve (AUC), and oral clearance (CL/F) as determined from APV concentrations observed in blood samples obtained at baseline, and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours during the BID regimens (FPV 1400mg BID, FPV 700mg/RTV 100 mg BID), and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 24 hours during the QD regimen (FPV 1400mg/RTV 100mg QD). As Groups A and B received the same regimens (albeit in different order), PK data for these two groups were collated, then assessed. For the same reason, PK data from Groups C and D regimens were collated before assessment, as were the PK data from Groups E and F.

Time frame: Day 14 of the FPV 1400mg BID, FPV 1400mg/RAL 400mg BID, FPV 700mg/RTV 100mg BID, FPV 700mg/RTV 100mg/RAL 400mg BID, FPV 1400mg/RTV 100mg QD, and FPV 1400mg/RTV 100mg QD plus RAL 400mg BID regimens

ArmMeasureValue (MEAN)
Group A & BCL/F: Fasting Steady-state Plasma Amprenavir (APV) Pharmacokinetics (PK) Following Administration of Fosamprenavir (FPV) 1400mg BID, FPV 700mg/Ritonavir (RTV) 100 mg BID, or FPV 1400mg/RTV 100mg QD With and Without Concurrent Raltegravir (RTG) 400mg BID.1.57 L/h
Group C & DCL/F: Fasting Steady-state Plasma Amprenavir (APV) Pharmacokinetics (PK) Following Administration of Fosamprenavir (FPV) 1400mg BID, FPV 700mg/Ritonavir (RTV) 100 mg BID, or FPV 1400mg/RTV 100mg QD With and Without Concurrent Raltegravir (RTG) 400mg BID.1.05 L/h
Group E & FCL/F: Fasting Steady-state Plasma Amprenavir (APV) Pharmacokinetics (PK) Following Administration of Fosamprenavir (FPV) 1400mg BID, FPV 700mg/Ritonavir (RTV) 100 mg BID, or FPV 1400mg/RTV 100mg QD With and Without Concurrent Raltegravir (RTG) 400mg BID.1.63 L/h
Primary

CL/F: Steady-state Plasma RTG PK Following Administration of RTG 400mg BID Alone and Following Co-administration With FPV 1400mg BID, FPV 700mg/RTV 100 mg BID, or FPV 1400mg/RTV 100mg QD

Amprenavir (APV) is the active ingredient/metabolite of Fosamprenavir (FPV). RAL minimum concentration (Cmin), maximum concentration (Cmax), area under the plasma concentration-time curve (AUC), and oral clearance (CL/F) as determined from RAL concentrations observed in blood samples obtained at baseline, and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours during the period when RAL 400mg BID was administered with the FPV-Containing BID regimens (FPV 1400mg BID, FPV 700mg/RTV 100 mg BID), and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 24 hours during the period when RAL 400mg BID was administered with the FPV QD regimen (FPV 1400mg/RTV 100mg QD). As Groups A and B received the same regimens (albeit in different order), PK data for these two groups were collated, then assessed. For the same reason, PK data from Groups C and D regimens were collated before assessment, as were the PK data from Groups E and F.

Time frame: Day 7 of the RAL 400mg BID regimen and Day 14 of the RAL 400mg/FPV 1400mg BID, RAL 400mg/FPV 700mg/RTV 100mg BID, and RAL 400mg BID Plus FPV 1400mg/RTV 100mg QD regimens

ArmMeasureValue (MEAN)
Group A & BCL/F: Steady-state Plasma RTG PK Following Administration of RTG 400mg BID Alone and Following Co-administration With FPV 1400mg BID, FPV 700mg/RTV 100 mg BID, or FPV 1400mg/RTV 100mg QD1.46 L/h
Group C & DCL/F: Steady-state Plasma RTG PK Following Administration of RTG 400mg BID Alone and Following Co-administration With FPV 1400mg BID, FPV 700mg/RTV 100 mg BID, or FPV 1400mg/RTV 100mg QD2.00 L/h
Group E & FCL/F: Steady-state Plasma RTG PK Following Administration of RTG 400mg BID Alone and Following Co-administration With FPV 1400mg BID, FPV 700mg/RTV 100 mg BID, or FPV 1400mg/RTV 100mg QD1.18 L/h
Primary

Cmin/Cmax: Fasting Steady-state Plasma Amprenavir (APV) Pharmacokinetics (PK) Following Admin of Fosamprenavir (FPV) 1400mg BID, FPV 700mg/Ritonavir (RTV) 100 mg BID, or FPV 1400mg/RTV 100mg QD With and Without Concurrent Raltegravir (RTG) 400mg BID.

Amprenavir (APV) is the active ingredient/metabolite of Fosamprenavir (FPV). APV minimum concentration (Cmin), maximum concentration (Cmax), area under the plasma concentration-time curve (AUC), and oral clearance (CL/F) as determined from APV concentrations observed in blood samples obtained at baseline, and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours during the BID regimens (FPV 1400mg BID, FPV 700mg/RTV 100 mg BID), and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 24 hours during the QD regimen (FPV 1400mg/RTV 100mg QD). As Groups A and B received the same regimens (albeit in different order), PK data for these two groups were collated, then assessed. For the same reason, PK data from Groups C and D regimens were collated before assessment, as were the PK data from Groups E and F.

Time frame: Day 14 of the FPV 1400mg BID, FPV 1400mg/RAL 400mg BID, FPV 700mg/RTV 100mg BID, FPV 700mg/RTV 100mg/RAL 400mg BID, FPV 1400mg/RTV 100mg QD, and FPV 1400mg/RTV 100mg QD plus RAL 400mg BID regimens

ArmMeasureGroupValue (MEAN)
Group A & BCmin/Cmax: Fasting Steady-state Plasma Amprenavir (APV) Pharmacokinetics (PK) Following Admin of Fosamprenavir (FPV) 1400mg BID, FPV 700mg/Ritonavir (RTV) 100 mg BID, or FPV 1400mg/RTV 100mg QD With and Without Concurrent Raltegravir (RTG) 400mg BID.Cmin (ng/mL)0.57 ng/mL
Group A & BCmin/Cmax: Fasting Steady-state Plasma Amprenavir (APV) Pharmacokinetics (PK) Following Admin of Fosamprenavir (FPV) 1400mg BID, FPV 700mg/Ritonavir (RTV) 100 mg BID, or FPV 1400mg/RTV 100mg QD With and Without Concurrent Raltegravir (RTG) 400mg BID.Cmax (ng/mL)0.73 ng/mL
Group C & DCmin/Cmax: Fasting Steady-state Plasma Amprenavir (APV) Pharmacokinetics (PK) Following Admin of Fosamprenavir (FPV) 1400mg BID, FPV 700mg/Ritonavir (RTV) 100 mg BID, or FPV 1400mg/RTV 100mg QD With and Without Concurrent Raltegravir (RTG) 400mg BID.Cmin (ng/mL)0.81 ng/mL
Group C & DCmin/Cmax: Fasting Steady-state Plasma Amprenavir (APV) Pharmacokinetics (PK) Following Admin of Fosamprenavir (FPV) 1400mg BID, FPV 700mg/Ritonavir (RTV) 100 mg BID, or FPV 1400mg/RTV 100mg QD With and Without Concurrent Raltegravir (RTG) 400mg BID.Cmax (ng/mL)0.86 ng/mL
Group E & FCmin/Cmax: Fasting Steady-state Plasma Amprenavir (APV) Pharmacokinetics (PK) Following Admin of Fosamprenavir (FPV) 1400mg BID, FPV 700mg/Ritonavir (RTV) 100 mg BID, or FPV 1400mg/RTV 100mg QD With and Without Concurrent Raltegravir (RTG) 400mg BID.Cmin (ng/mL)0.50 ng/mL
Group E & FCmin/Cmax: Fasting Steady-state Plasma Amprenavir (APV) Pharmacokinetics (PK) Following Admin of Fosamprenavir (FPV) 1400mg BID, FPV 700mg/Ritonavir (RTV) 100 mg BID, or FPV 1400mg/RTV 100mg QD With and Without Concurrent Raltegravir (RTG) 400mg BID.Cmax (ng/mL)0.82 ng/mL
Primary

Cmin/Cmax: Steady-state Plasma RTG PK Following Admin of RTG 400mg BID Alone and Following Co-administration With FPV 1400mg BID, FPV 700mg/RTV 100 mg BID, or FPV 1400mg/RTV 100mg QD

Amprenavir (APV) is the active ingredient/metabolite of Fosamprenavir (FPV). RAL minimum concentration (Cmin), maximum concentration (Cmax), area under the plasma concentration-time curve (AUC), and oral clearance (CL/F) as determined from RAL concentrations observed in blood samples obtained at baseline, and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours during the period when RAL 400mg BID was administered with the FPV-Containing BID regimens (FPV 1400mg BID, FPV 700mg/RTV 100 mg BID), and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 24 hours during the period when RAL 400mg BID was administered with the FPV QD regimen (FPV 1400mg/RTV 100mg QD). As Groups A and B received the same regimens (albeit in different order), PK data for these two groups were collated, then assessed. For the same reason, PK data from Groups C and D regimens were collated before assessment, as were the PK data from Groups E and F.

Time frame: Day 7 of the RAL 400mg BID regimen and Day 14 of the RAL 400mg/FPV 1400mg BID, RAL 400mg/FPV 700mg/RTV 100mg BID, and RAL 400mg BID Plus FPV 1400mg/RTV 100mg QD regimens

ArmMeasureGroupValue (MEAN)
Group A & BCmin/Cmax: Steady-state Plasma RTG PK Following Admin of RTG 400mg BID Alone and Following Co-administration With FPV 1400mg BID, FPV 700mg/RTV 100 mg BID, or FPV 1400mg/RTV 100mg QDCmin (ng/mL)0.62 ng/mL
Group A & BCmin/Cmax: Steady-state Plasma RTG PK Following Admin of RTG 400mg BID Alone and Following Co-administration With FPV 1400mg BID, FPV 700mg/RTV 100 mg BID, or FPV 1400mg/RTV 100mg QDCmax (ng/mL)0.72 ng/mL
Group C & DCmin/Cmax: Steady-state Plasma RTG PK Following Admin of RTG 400mg BID Alone and Following Co-administration With FPV 1400mg BID, FPV 700mg/RTV 100 mg BID, or FPV 1400mg/RTV 100mg QDCmin (ng/mL)0.64 ng/mL
Group C & DCmin/Cmax: Steady-state Plasma RTG PK Following Admin of RTG 400mg BID Alone and Following Co-administration With FPV 1400mg BID, FPV 700mg/RTV 100 mg BID, or FPV 1400mg/RTV 100mg QDCmax (ng/mL)0.49 ng/mL
Group E & FCmin/Cmax: Steady-state Plasma RTG PK Following Admin of RTG 400mg BID Alone and Following Co-administration With FPV 1400mg BID, FPV 700mg/RTV 100 mg BID, or FPV 1400mg/RTV 100mg QDCmin (ng/mL)0.75 ng/mL
Group E & FCmin/Cmax: Steady-state Plasma RTG PK Following Admin of RTG 400mg BID Alone and Following Co-administration With FPV 1400mg BID, FPV 700mg/RTV 100 mg BID, or FPV 1400mg/RTV 100mg QDCmax (ng/mL)1.06 ng/mL
Secondary

Number of Participants Who Experienced Adverse Events

Safety/tolerability data included all adverse events (AEs) reported within the time frame of each regimen evaluated. The intent was to compare AE's for each sequence and not for each regimen. 3The regimens for which AE information was culled were: * RAL 400mg BID alone * FPV 1400mg BID alone * FPV 700mg/RTV 100 mg BID alone * FPV 1400mg/RTV 100mg QD alone * FPV 1400mg BID combined with RAL 400mg BID * FPV 700mg/RTV 100 mg BID combined with RAL 400mg BID * FPV 1400mg/RTV 100mg QD combined with RAL 400mg BID The severity of reported AEs was graded according to DAIDS criteria, Version 1.0 (National Institute of Allergy and Infectious Diseases (NIAID). Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 1.0. Division of Acquired Immunodeficiency Syndrome (DAIDS), Washington D.C.; 2004).

Time frame: Day 0 through Day 49

ArmMeasureValue (NUMBER)
Group A & BNumber of Participants Who Experienced Adverse Events3 participants
Group C & DNumber of Participants Who Experienced Adverse Events3 participants
Group E & FNumber of Participants Who Experienced Adverse Events4 participants
Group DNumber of Participants Who Experienced Adverse Events4 participants
Group ENumber of Participants Who Experienced Adverse Events5 participants
Group FNumber of Participants Who Experienced Adverse Events5 participants

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026