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

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
    

Intervention name(s): Raltegravir; Fosamprenavir; Ritonavir
Intervention type(s): Drug; Drug; Drug
Intervention description(s): 400mg BID; 1400mg BID, 700 mg BID or 1400 mg QD; 100 mg BID or QD
Other intervention name(s): Isentress; MK-0518; Lexiva; Norvir
Intervention MeSH terms: Ritonavir; Fosamprenavir; Raltegravir Potassium
Allocation: Randomized
Intervention model: Factorial Assignment
Masking: None (Open Label)
Keywords: Healthy Subjects; Pharmacokinetics study; Pharmacokinetics of medications