Pharmacokinetics of Oxycodone and PF614 Co-Administered With Nafamostat
Condition: Pharmacokinetics
Study type: Interventional
Phase: Phase 1

Summary: 
      A single dose study to assess the pharmacokinetics (PK) of oxycodone, when PF614 is solution
      is administered alone and with nafamostat as an immediate-release (IR) solution and/or
      extended-release (ER) capsule prototypes.
    

Detailed description: 
      This is a single center, randomized, open-label formulation development study for the
      nafamostat formulation (IR solution and/or ER prototype capsules) and will have the option to
      assess the effect of food on a selected formulation of healthy subjects. Parts 1 and 2 are
      planned to enroll a total of 64 healthy subjects, with roughly equal number of males and an
      even number of females with roughly equal number of males and females in each cohort if
      possible. Subjects will be randomized to regimen stratified by gender prior to first dose.
      Cohort 1 and Cohort 6 will consist of 8 subjects who will receive dosing on two occasions in
      a 2-period sequential design. Cohorts 2 to 5 and Cohorts 7 to 10 will consist of 6 subjects
      in each cohort and they will receive dosing on a single occasion only. Cohorts 2 to 5 and
      Cohorts 7 to 10 can be dosed in parallel after Cohort 1 dosing.

      Part 1 (with naltrexone blockade) and Part 2 (without naltrexone), Cohorts 1-10, were later
      expanded to include 6-13 subjects each.

      In Cohort 1 and Cohort 6, subjects will receive the PF614 solution alone and concomitantly
      with nafamostat. In addition, prior to and following each regimen in all periods, subjects
      will receive blocking doses of the opiate antagonist naltrexone to reduce the opioid-related
      side effects.

      Interim reviews of the safety and PK data for oxycodone and PF614 to 48h post-dose will take
      place after Cohorts 1 and 6, Cohorts 2 and 7, Cohorts 3 and 8 and Cohorts 4 and 9 to decide
      upon the following: nafamostat formulation to dose in the subsequent period; After Cohorts 3
      and 8 only: The prandial status (fed vs fasted) for Cohort 4 and Cohort 9.

      Extended-release prototype capsule formulations will be selected from a 2-dimensional design
      space describing formulation variables for release rate and dose; however the maximum
      nafamostat dose to be administered with be 10 mg.

      Part 3 (N=12 subjects) was added as a 7-period open-label cross-over study to assess the
      selected combination of nafamostat IR solution and/or ER prototype capsule(s) identified from
      Part 2 who were administered with PF614 solution at increasing dose levels to simulate
      overdose. All subjects in Part 3 received naltrexone blockade.
    

Intervention name(s): PF614 solution; Naltrexone Hydrochloride; Nafamostat Mesylate
Intervention type(s): Drug; Drug; Drug
Intervention description(s): PF614 solution is an oxycodone prodrug; Naltrexone 50 mg has been selected to be administered on Day -1 (single dose), Day 1 (BID), and Day 2 (single-dose) to reduce opioid-related adverse effects.; Maximum dose of 10 mg nafamostat co-administered with PF614 solution. Nafamostat will be dosed as an immediate-release (IR) solution or as prototype extended-release (ER) capsules.
Other intervention name(s): PRF06104; Oxycodone prodrug; ReVia; Futhan
Intervention MeSH terms: Nafamostat; Naltrexone; Oxycodone
Allocation: Randomized
Intervention model: Sequential Assignment
Masking: None (Open Label)
Primary purpose: Treatment