Study of PF614 Compared to OxyContin® in Healthy Volunteers (PF614-101)

NCT02454712 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: PF614-101
• Study Type: interventional
• Target: 64
• Locations: 1 country
• Sites: 1

Brief Summary

PF614 is an oxycodone prodrug that is designed for extended-release of oxycodone comparable to OxyContin. This Single Ascending Dose (SAD) study is designed to assess the safety and pharmacokinetics (PK) of PF614 in comparison to standard doses of OxyContin.

Conditions

Healthy

Keywords

Prodrug; PF614; oxycodone extended-release; oral

Outcome Measures

Primary Outcomes (1)

• Safety

  Adverse events

  30 days

Secondary Outcomes (9)

• Pharmacokinetics (Cmax)

  Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60 and 72 hours post dose

• Pharmacokinetics (Tmax)

  Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60 and 72 hours post dose

• Pharmacokinetics (AUC)

  Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60 and 72 hours post dose

• Dose Selection (Identify doses of PF614 with pharmacokinetics comparable to OxyContin)

  4 days

• Prodrug Fragments (plasma concentration)

  Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60 and 72 hours post dose

Study Arms (2)

PF614

EXPERIMENTAL

PF614 is the drug under evaluation. Doses may range from 15 mg to 640 mg. N=6 subjects per cohort. For Cohort 7, N=16 subjects in crossover study ± naltrexone.

Drug: PF614; Drug: Naltrexone Hydrochloride

Oxycodone extended-release (OxyContin)

ACTIVE COMPARATOR

Initial dose (Cohort 1) will be 10 mg. Subsequent doses will be 10, 20, 40, or 80 mg. N=2 subjects per cohort. Active comparator will not be used in Cohort 7.

Drug: Oxycodone extended-release; Drug: Naltrexone Hydrochloride

Interventions

PF614 DRUG

PF614 is an oxycodone prodrug

Also known as: PRF06104

PF614

Oxycodone extended-release DRUG

Oxycodone extended-release is the comparator drug

Also known as: OxyContin

Oxycodone extended-release (OxyContin)

Naltrexone Hydrochloride DRUG

Naltrexone HCl tablets, 50 mg, will be used to block high dose opioid effects in healthy volunteers

Also known as: ReVia

Oxycodone extended-release (OxyContin); PF614

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Males and females, ages 18-50 years (inclusive) in good general health;
• Body mass index (BMI) between 18.0 and 32.0 kg/m2 (inclusive);
• Minimum weight of 50.0 kg, inclusive;
• Subjects must have a negative screen for drugs of abuse, cotinine, alcohol, hepatitis B-surface antigen, hepatitis C antibody and antibodies against HIV 1 and 2;
• Female subjects must have a negative serum pregnancy test at screening and a negative pregnancy test on Day -1;
• Females of childbearing potential and males and their female partner(s) of childbearing potential must agree to use 2 forms of contraception, 1 of which must be a barrier method, during the study and for 90 days after the last drug administration. Acceptable barrier forms of contraception are condom and diaphragm. Acceptable nonbarrier forms of contraception for this study are a nonhormonal intrauterine device (IUD), oral contraceptives and/or spermicide;
• Male subjects must agree not to donate sperm throughout the study and for 90 days after the last study drug administration;
• Subjects must have normal or no evidence of clinically significant findings in physical examination and 12-lead electrocardiogram (ECG) according to the Investigator, and normal vital signs (respiratory rate between 10 and 18 breaths per minute, blood pressure between 100-139/50-89 mmHg, heart rate between 40-100 beats per minute, temperature between 96.44°F and 100.04°F (between 35.8°C and 37.8°C), and oxygen saturation (SpO2) \> 97% in the absence of supplemental oxygen;
• Clinical laboratory values must be within the normal limits as defined by the clinical laboratory, unless the Investigator decides that out-of-range values are not clinically significant;
• Subjects must be able to provide meaningful written informed consent;
• Subjects must be willing and able to follow study instructions and be likely to complete all study requirements.

You may not qualify if:

• History of allergy or sensitivity to oxycodone, OxyContin, any other opiate, naltrexone, or naloxone;
• History of loud snoring or sleep apnea;
• History of medical problems encountered with opioid therapy;
• Urinary cotinine levels indicative of smoking or history of regular use of tobacco-containing or nicotine-containing products within 2 months prior to screening;
• History of alcoholism or drug abuse (prescription or illicit drugs) according to Diagnostic and Statistical Manual IV-Text Revision (DSM IV-TR) criteria;
• Use of prescription medications within 14 days of study drug administration, except for contraceptive medications used by female subjects; use of over-the-counter (OTC) medications within 7 days prior to study drug administration;
• Use of any opioid within 30 days prior to screening;
• Donation of blood within 60 days prior to screening;
• Donation of plasma, platelets, or white blood cells within 7 days prior to dosing;
• Acute illness (eg, gastrointestinal illness, infection such as influenza, upper respiratory tract infection, or known inflammatory process) within 7 days of dosing
• History of gastrointestinal disturbance requiring frequent use of antacid;
• History of clinically significant gastrointestinal disease and/or surgery which would result in the subject's inability to absorb or metabolize the study drug (eg, gastrectomy, gastric bypass, cholecystectomy);
• Anticipated need for surgery or hospitalization during the study or follow-up period;
• Dosing with an investigational drug or participation in an investigation device study within 30 days or 5 half-lives of first dose of the study drug;
• Women who are lactating;

Sponsors & Collaborators

• Ensysce Biosciences: lead
• PRA Health Sciences: collaborator

Study Sites (1)

PRA Health Sciences - Early Development Services

Lenexa, Kansas, 66219, United States

Location

Related Publications (2)

• Schmidt WK, Dickerson DS, Fisher DM, Kirkpatrick DL. First-in-human pharmacokinetics & safety study of PF614: orally activated oxycodone prodrug. Anesth Analg. 2017;124(5):752-753.

  BACKGROUND

• Kirkpatrick DL, Evans C, Pestano LA, Millard J, Johnston M, Mick E, Schmidt WK. Clinical evaluation of PF614, a novel TAAP prodrug of oxycodone, versus OxyContin in a multi-ascending dose study with a bioequivalence arm in healthy volunteers. Clin Transl Sci. 2024 Mar;17(3):e13765. doi: 10.1111/cts.13765.

  PMID: 38511523 BACKGROUND

MeSH Terms

Interventions

Oxycodone; Naltrexone

Intervention Hierarchy (Ancestors)

Codeine; Morphine Derivatives; Morphinans; Opiate Alkaloids; Alkaloids; Heterocyclic Compounds; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds; Naloxone

Study Officials

• William K Schmidt, PhD

  Ensysce Biosciences

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 12, 2015
• First Posted: May 27, 2015
• Study Start: November 16, 2016
• Primary Completion: January 18, 2018
• Study Completion: January 18, 2018
• Last Updated: October 2, 2024

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)