Clinical trial NCT00764465
Conditions: Healthy
Keywords: Healthy Subjects Pharmacokinetics study Pharmacokinetics of medications
Sponsor: Garden State Infectious Disease Associates, PA
Start date: 2008-10-01; Completion date: 2008-12-01
Enrollment: 45 participants; Allocation: RANDOMIZED; Intervention model: FACTORIAL

Brief summary:
To date, no study has investigated whether there is a drug interaction between the protease inhibitor fosamprenavir and the entry inhibitor maraviroc. COL112237 is a randomized, open-label, 6-arm, 3-period, drug interaction study to assess steady-state plasma amprenavir (APV) and maraviroc (MVC) pharmacokinetics in 48 healthy, HIV-negative adults after administration of a 7-day regimen of MVC 300mg 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 MVC 300mg 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 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 Days 1 to 7 Period 2 Days 1-14 Period 3 Days 1-14

A 8 MVC 300mg BID; FPV 1400mg BID; FPV 1400mg BID \& MVC 300mg BID

B 8 MVC 300mg BID; FPV 1400mg BID \& MVC 300mg BID; FPV 1400mg BID

C 8 MVC 300mg BID; FPV 700mg BID \& RTV 100mg BID; FPV 700mg BID \& RTV 100mg BID \&MVC 300mg BID

D 8 MVC 300mg BID; FPV 700mg BID \& RTV 100mg BID \& MVC 300mg BID; FPV 700mg BID \& RTV 100mg BID

E 8 MVC 300mg BID; FPV 1400mg QD \& RTV 100mg QD; FPV 1400mg QD \& RTV 100mg QD \& MVC 300mg BID

F 8 MVC 300mg BID; FPV 1400mg QD \& RTV 100mg QD \& MVC 300mg BID; FPV 1400mg QD \& RTV 100mg QD

Study subjects will enter the clinic in the morning prior to dosing 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 maraviroc(MVC) 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 and MVC concentrations will be analyzed using a validated high-performance liquid chromatography method with tandem mass spectrometric detection (HPLC/MS/MS). Plasma APV and MVC 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.

Arms: arm 1: Period 1-Maraviroc 300mg BID Period 2- Fosamprenavir 1400mg BID Period 3- Fosamprenavir 1400mg BID + Maraviroc 300mg BID arm 2: Period 1-Maraviroc 300mg BID Period 2-Fosamprenavir 1400mg BID + Maraviroc 300mg BID Period 3-Fosamprenavir 1400mg BID arm 3: Period 1-Maraviroc 300mg BID Period 2-Fosamprenavir 700mg BID + Ritonavir 100mg BID Period 3-Fosamprenavir 700mg BID + Ritonavir 100mg BID + Maraviroc 300mg BID arm 4: Period 1-Maraviroc 300mg BID Period 2-Fosamprenavir 700mg BID + Ritonavir 100mg BID + Maraviroc 300mg BID Period 3-Fosamprenavir 700mg BID + Ritonavir 100mg BID arm 5: Period 1-Maraviroc 300mg BID Period 2-Fosamprenavir 1400mg QD + Ritonavir 100mg QD Period 3- Fosamprenavir 1400mg QD + Ritonavir 100mg QD + Maraviroc 300mg BID arm 6: Period 1-Maraviroc 300mg BID Period 2-Fosamprenavir 1400mg QD + Ritonavir 100mg QD + Maraviroc 300mg BID Period 3-Fosamprenavir 1400mg QD + Ritonavir 100mg QD
Interventions: intervention 1: Maraviroc intervention 2: Fosamprenavir intervention 3: Ritonavir
Intervention descriptions: intervention 1: 300 mg BID intervention 2: 1400 mg BID, 700 mg BID or 1400 mg QD intervention 3: 100 mg BID, 100 mg QD

Protocol documents: