An Interaction Study to Assess Drug Levels in Healthy Adult Subjects
Condition: Healthy
Study type: Interventional
Phase: Phase 2

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.
    

Intervention name(s): Maraviroc; Fosamprenavir; Ritonavir
Intervention type(s): Drug; Drug; Drug
Intervention description(s): 300 mg BID; 1400 mg BID, 700 mg BID or 1400 mg QD; 100 mg BID, 100 mg QD
Other intervention name(s): Lexiva; Norvir
Intervention MeSH terms: Ritonavir; Fosamprenavir; Maraviroc
Allocation: Randomized
Intervention model: Factorial Assignment
Masking: None (Open Label)
Keywords: Healthy Subjects; Pharmacokinetics study; Pharmacokinetics of medications