Healthy Volunteers
Conditions
Keywords
Prodrug, PF614, OxyContin, oral
Brief summary
This is a single-center study incorporating 2 parts: A Multiple Ascending Dose Study (Part A) and a comparative Bioavailability/Bioequivalence and Food Effect study (Part B). Both parts of the study will be conducted in healthy adult subjects.
Detailed description
This study is intended to evaluate the pharmacokinetics of OxyContin (oxycodone ER) and PF614, as well as PF614 fragments, following administration of multiple ascending doses of PF614, and to compare to steady-state pharmacokinetics to those of OxyContin. (Part A) In addition, oral bioavailability of oxycodone derived from single doses of PF614 of the to-be-marketed capsule formulation will be compared to that of the reference drug, OxyContin, in the fasted and fed condition. A pivotal food effect assessment will be incorporated into the study to determine the impact of a high fat meal on the bioavailability of oxycodone, following oral single-dose administration of PF614 (Part B).
Interventions
Sponsors
PRA Health Sciences
Ensysce Biosciences
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Part A will utilize a randomized, open label, multiple-ascending dose design with up to 3 separate dose groups of 8 subjects per group. Part B will utilize an open-label, single-dose, randomized, 4-way crossover design with 13 subjects in each treatment sequence.
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
Yes
Inclusion criteria
* Males or females, ages 18-50 years in good general health, * BMI between 18 and 32 kg/m (inclusive) * Subjects must have a negative screen for drugs of abuse, nicotine, alcohol, Hepatitis B, Hepatitis C, and HIV. * Female subjects of child bearing potential must have a negative serum pregnancy test at randomization * Females must be of non-child bearing potential (e.g. postmenopausal) or of childbearing potential and agree to use a highly effective form of contraception from the time of screening to two weeks after last dose of study medication. * Subjects must have normal findings in a physical examination and 12 lead ECG and normal Vital Signs * Clinical laboratory values must be Within Normal limits as defined by the clinical laboratory * Subjects must be able to provide coherent written informed consent * Subjects must be willing and able to follow study instructions and be likely to complete all study requirements.
Exclusion criteria
* History of allergy or sensitivity to oxycodone * History of loud snoring or sleep apnea * History of medical problems encountered with opioid therapy * Urinary cotinine levels indicative of smoking or history of smoking or regular tobacco use with 2 months prior to screening * History of alcoholism or drug abuse * Use of prescription medications within 14 days of study drug administration with exception of contraceptives used by female subjects * Use of any opioid within 30 days prior to screening * History of allergy or sensitivity to naltrexone * History of allergy or sensitivity to naloxone * Donation of blood within 30 days prior to screening * Donation of plasma within 30 days prior to screening * Acute illness at admission of clinical study unit * History of GI disturbance requiring use of antacid twice weekly or more * Females who are breastfeeding * Anticipated need for surgery or hospitalization during the study * Enrollment in an investigational drug study within 30 days prior to screening * Any condition that in the Investigator's opinion puts the subject at significant risk, could confound the study results, or may interfere significantly with the subject's participation in the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Bioavailability and Bioequivalence | PK sampling time points 0, 30 minutes; 1, 2, 3, 4, 6, 8, and 12 hours | Bioavailability and Bioequivalence of single oral doses of PF614 prodrug and oxycodone derived from from PF614 vs. oxycodone derived from OxyContin in healthy adult subjects (Part B) |
| Pharmacokinetics Cmax, Steady State | PK sampling time points 0, 30 minutes; 1, 2, 3, 4, 6, 8, and 12 hours | Maximum (peak) plasma concentration at steady-state on Day 5 |
| Pharmacokinetics Tmax, Steady State | PK sampling time points 0, 30 minutes; 1, 2, 3, 4, 6, 8, and 12 hours | Time to maximum plasma concentration on Day 5 |
| Pharmacokinetics t1/2 [Half-life] | PK sampling time points 0, 30 minutes; 1, 2, 3, 4, 6, 8, and 12 hours | Terminal elimination half-life |
| Pharmacokinetics Vz/F [Volume of Distribution] | PK sampling time points 0, 30 minutes; 1, 2, 3, 4, 6, 8, and 12 hours | Apparent volume of distribution during the terminal-elimination phase |
| Pharmacokinetics elimination rate | PK sampling time points 0, 30 minutes; 1, 2, 3, 4, 6, 8, and 12 hours | Terminal elimination rate/constant |
| Pharmacokinetics Ctrough [Minimum Plasma Concentration before next dose] | Prior to dosing on Days 2, 3, and 4 | Concentrations prior to dosing |
| Pharmacokinetics Part B AUC | PK sampling time points 0, 30 minutes; 1, 2, 3, 4, 6, 8, and 12 hours | Area under the concentration-time curve from the time of dosing extrapolated to time infinity in fed vs fasted state |
| Pharmacokinetics Part B AUC 0-t | PK sampling time points 0, 30 minutes; 1, 2, 3, 4, 6, 8, and 12 hours | Area under the concentration-time curve from the time of dosing to the last measurable concentration in fed vs fasted state |
| Pharmacokinetics Part B Cmax | PK sampling time points 0, 30 minutes; 1, 2, 3, 4, 6, 8, and 12 hours | Maximum (peak) plasma concentration in fed vs fasted state |
| Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] | 30 days | Adverse Events, Significant Adverse Events, Adverse Events leading to discontinuation |
| Pharmacokinetics AUC [Area Under the Curve] | Full PK sampling time points will be 0, 30 minutes; 1, 2, 3, 4, 6, 8, and 12 hours | Area under the concentration-time curve from the time of dosing to the start of the next dosing interval using PF614 concentrations and oxycodone concentrations in plasma. |
| Pharmacokinetics Cmax [Maximum Plasma Concentration] | PK sampling time points will be 0, 30 minutes; 1, 2, 3, 4, 6, 8, and 12 hours | Maximum (peak) plasma concentration first dose |
| Pharmacokinetics Tlag [Time to first measurable plasma concentration] | PK sampling time points will be 0, 30 minutes; 1, 2, 3, 4, 6, 8, and 12 hours | Time prior to the time corresponding to the first measurable (non-zero) concentration |
| Pharmacokinetics Tmax [Time to maximum plasma concentration] | PK sampling time points 30 minutes; 1, 2, 3, 4, 6, 8, and 12 hours | Time to maximum plasma concentration on Day 1 (first dose) |
| Pharmacokinetics AUC, Steady State | PK sampling time points 0, 30 minutes; 1, 2, 3, 4, 6, 8, and 12 hours | Steady-state (Day 5) area under the concentration-time curve from the time of dosing extrapolated to time infinity |
| Pharmacokinetics CL/F [Clearance] | PK sampling time points 0, 30 minutes; 1, 2, 3, 4, 6, 8, and 12 hours | Apparent total systemic clearance |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics Part B pAUC | PK sampling time points 0, 30 minutes; 1, 2, 3, 4, 6, 8, and 12 hours | Partial area under the concentration-time curve from the time of dosing to 12 hours post dose |
| Pharmacokinetics Part B Tlag | PK sampling time points 0, 30 minutes; 1, 2, 3, 4, 6, 8, and 12 hours | Time prior to the time corresponding to the first measurable dose (non-zero) concentration |
| Pharmacokinetics Part B Tmax | PK sampling time points 0, 30 minutes; 1, 2, 3, 4, 6, 8, and 12 hours | Time to maximum plasma concentration on Day 1 (first dose) |
| Pharmacokinetics Part B t1/2 | PK sampling time points 0, 30 minutes; 1, 2, 3, 4, 6, 8, and 12 hours | Terminal elimination half life |
| Pharmacokinetics Part B Vz/F | PK sampling time points 0, 30 minutes; 1, 2, 3, 4, 6, 8, and 12 hours | Apparent volume of distribution during the terminal elimination phase |
| Pharmacokinetics Part B Terminal elimination rate | PK sampling time points 0, 30 minutes; 1, 2, 3, 4, 6, 8, and 12 hours | Terminal elimination rate constant |
| Plasma Concentration of inactive metabolic fragment #1 | PK sampling time points 0, 30 minutes; 1, 2, 3, 4, 6, 8, and 12 hours | Evaluate plasma concentrations of PFR06082 (Part A only) |
| Plasma Concentration of inactive metabolic fragment #2 | PK sampling time points 0, 30 minutes; 1, 2, 3, 4, 6, 8, and 12 hours | Evaluate plasma concentrations of PFR06110 (Part A only) |
| Pharmacokinetics Part B CL/F | PK sampling time points 0, 30 minutes; 1, 2, 3, 4, 6, 8, and 12 hours | Apparent total systemic clearance |
Countries
United States
Outcome results
None listed