Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02454712
Recruitment Status : Completed
First Posted : May 27, 2015
Last Update Posted : July 26, 2018
Sponsor:
Collaborator:
PRA Health Sciences
Information provided by (Responsible Party):
Ensysce Biosciences

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.

Condition or disease Intervention/treatment Phase
Healthy Drug: PF614 Drug: Oxycodone extended-release Drug: Naltrexone Hydrochloride Phase 1

Detailed Description:
This will be a Phase 1 randomized, single-center, SAD study in 6 cohorts of 8 healthy male and/or female subjects each (Cohorts 1-6) plus 16 enrolled healthy male and/or female subjects (Cohort 7). The study will evaluate the safety and PK of PF614 and the PK of oxycodone at doses sufficient to characterize the extent to which plasma oxycodone is produced and maintained following oral ingestion of PF614. The PK of the prodrug fragments will also be evaluated. There will be a parallel study arm in each cohort dosed that will use oral OxyContin® as an active comparator. Subjects will receive PF614 (n=6) or OxyContin as comparator (n=2) orally in the fasted state. In addition, all subjects starting with Cohort 1C will receive naltrexone at 14 hours pre-dose, 2 hours pre-dose and 10 hours post dose to block the effects of oxycodone. The starting dose for administration of PF614 will be 15 mg. The lowest available dose of OxyContin, 10 mg, will be used as the comparator in the first cohort. PK assessments will be conducted after each cohort to compare the oxycodone area under curve (AUC) of PF614 and OxyContin to determine the most appropriate dose for the subsequent cohorts. In Cohort 6 (fed subjects), all subjects (n=8) will receive the same PF614 and naltrexone doses as administered in Cohort 5 to evaluate the PK and safety of PF614 in fed vs. fasted state. Subjects in Cohort 6 will receive a Food and Drug Administration-defined high-fat, high-calorie breakfast 30 minutes prior to study drug administration. In Cohort 7, treatments will be administered in a cross-over study design across 2 periods. All subjects (n=16 enrolled; estimated n=12 completers) will receive the same PF614 dose as administered in Cohort 1 (15 mg) with and without naltrexone to evaluate the potential effect of naltrexone on the plasma PK of PF614 and oxycodone. Cohort 7, Period 1 subjects may return for their cross-over treatments in Period 2 after a minimum of 12 days after receiving their initial Cohort 7 doses.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 64 participants
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1, Single-Center, Dose-Escalation Study to Determine the Safety and Pharmacokinetics of a Single Oral Dose of PF614 in Healthy Subjects Compared to OxyContin®
Actual Study Start Date : November 16, 2016
Actual Primary Completion Date : January 8, 2018
Actual Study Completion Date : January 10, 2018

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: PF614
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
PF614 is an oxycodone prodrug
Other Name: PRF06104

Drug: Naltrexone Hydrochloride
Naltrexone HCl tablets, 50 mg, will be used to block high dose opioid effects in healthy volunteers
Other Name: ReVia

Active Comparator: Oxycodone extended-release (OxyContin)
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
Oxycodone extended-release is the comparator drug
Other Name: OxyContin

Drug: Naltrexone Hydrochloride
Naltrexone HCl tablets, 50 mg, will be used to block high dose opioid effects in healthy volunteers
Other Name: ReVia




Primary Outcome Measures :
  1. Safety [ Time Frame: 30 days ]
    Adverse events


Secondary Outcome Measures :
  1. Pharmacokinetics (Cmax) [ Time Frame: 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 ]
    Peak plasma concentrations of oxycodone derived from PF614 and OxyContin

  2. Pharmacokinetics (Tmax) [ Time Frame: 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 ]
    Time to peak plasma concentrations of oxycodone derived from PF614 and OxyContin

  3. Pharmacokinetics (AUC) [ Time Frame: 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 ]
    Area under the plasma concentration vs. time curve (AUC) for oxycodone derived from PF614 and OxyContin

  4. Dose Selection (Identify doses of PF614 with pharmacokinetics comparable to OxyContin) [ Time Frame: 4 days ]
    Identify doses of PF614 with pharmacokinetics comparable to OxyContin

  5. Prodrug Fragments (plasma concentration) [ Time Frame: 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 ]
    Evaluate appearance and plasma concentrations of metabolic fragments derived from PF614

  6. Pharmacokinetics (Cmax) in fed vs. fasted state [ Time Frame: 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 ]
    Peak plasma concentrations of oxycodone derived from PF614

  7. Pharmacokinetics (Tmax) in fed vs. fasted state [ Time Frame: 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 ]
    Time to peak plasma concentrations of oxycodone derived from PF614

  8. Pharmacokinetics (AUC) in fed vs. fasted state [ Time Frame: 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 ]
    Area under the plasma concentration vs. time curve (AUC) for oxycodone derived from PF614

  9. Effect of naltrexone on PF614 and oxycodone plasma PK in a crossover design [ Time Frame: 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 ]
    Cmax and AUC of plasma oxycodone



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 50 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. Males and females, ages 18-50 years (inclusive) in good general health;
  2. Body mass index (BMI) between 18.0 and 32.0 kg/m2 (inclusive);
  3. Minimum weight of 50.0 kg, inclusive;
  4. 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;
  5. Female subjects must have a negative serum pregnancy test at screening and a negative pregnancy test on Day -1;
  6. 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;
  7. Male subjects must agree not to donate sperm throughout the study and for 90 days after the last study drug administration;
  8. 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;
  9. 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;
  10. Subjects must be able to provide meaningful written informed consent;
  11. Subjects must be willing and able to follow study instructions and be likely to complete all study requirements.

Exclusion Criteria:

  1. History of allergy or sensitivity to oxycodone, OxyContin, any other opiate, naltrexone, or naloxone;
  2. History of loud snoring or sleep apnea;
  3. History of medical problems encountered with opioid therapy;
  4. Urinary cotinine levels indicative of smoking or history of regular use of tobacco-containing or nicotine-containing products within 2 months prior to screening;
  5. History of alcoholism or drug abuse (prescription or illicit drugs) according to Diagnostic and Statistical Manual IV-Text Revision (DSM IV-TR) criteria;
  6. 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;
  7. Use of any opioid within 30 days prior to screening;
  8. Donation of blood within 60 days prior to screening;
  9. Donation of plasma, platelets, or white blood cells within 7 days prior to dosing;
  10. Acute illness (eg, gastrointestinal illness, infection such as influenza, upper respiratory tract infection, or known inflammatory process) within 7 days of dosing
  11. History of gastrointestinal disturbance requiring frequent use of antacid;
  12. 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);
  13. Anticipated need for surgery or hospitalization during the study or follow-up period;
  14. 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;
  15. Women who are lactating;
  16. Any other condition, that, in the Investigator's opinion, (i) puts the subject at increased risk, (ii) could confound the study results (iii) may interfere significantly with the subject's participation in the study or (IV) has the potential to limit the subject's ability to complete the study.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02454712


Locations
Layout table for location information
United States, Kansas
PRA Health Sciences - Early Development Services
Lenexa, Kansas, United States, 66219
Sponsors and Collaborators
Ensysce Biosciences
PRA Health Sciences
Investigators
Layout table for investigator information
Study Director: William K Schmidt, PhD Ensysce Biosciences
Layout table for additonal information
Responsible Party: Ensysce Biosciences
ClinicalTrials.gov Identifier: NCT02454712    
Other Study ID Numbers: PF614-101
First Posted: May 27, 2015    Key Record Dates
Last Update Posted: July 26, 2018
Last Verified: July 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Ensysce Biosciences:
Prodrug
PF614
oxycodone extended-release
oral
Additional relevant MeSH terms:
Layout table for MeSH terms
Naltrexone
Oxycodone
Analgesics, Opioid
Narcotics
Central Nervous System Depressants
Physiological Effects of Drugs
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Alcohol Deterrents
Narcotic Antagonists