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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

Tracking Information
First Submitted Date  ICMJE May 12, 2015
First Posted Date  ICMJE May 27, 2015
Last Update Posted Date July 26, 2018
Actual Study Start Date  ICMJE November 16, 2016
Actual Primary Completion Date January 8, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 25, 2018)
Safety [ Time Frame: 30 days ]
Adverse events
Original Primary Outcome Measures  ICMJE
 (submitted: May 22, 2015)
Safety and tolerability (Number of participants with adverse events) [ Time Frame: 30 days ]
Number of participants with adverse events including out-of-range clinical laboratory measures, vital signs, ECG, and spontaneous adverse event reports throughout the 30 day study period.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: December 2, 2017)
  • 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
  • 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
  • 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
  • Dose Selection (Identify doses of PF614 with pharmacokinetics comparable to OxyContin) [ Time Frame: 4 days ]
    Identify doses of PF614 with pharmacokinetics comparable to OxyContin
  • 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
  • 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
  • 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
  • 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
  • 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
Original Secondary Outcome Measures  ICMJE
 (submitted: May 22, 2015)
  • 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
  • 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
  • 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
  • Dose Selection (Identify doses of PF614 with pharmacokinetics comparable to OxyContin) [ Time Frame: 4 days ]
    Identify doses of PF614 with pharmacokinetics comparable to OxyContin
  • Food Effect (Ratio of Cmax in Fed vs. Fasted states) [ Time Frame: 4 days ]
    Preliminary assessment of the effect of food on the single dose Cmax of oxycodone derived from PF614 and oxycodone
  • Food Effect (Ratio of AUC in Fed vs. Fasted states) [ Time Frame: 4 days ]
    Preliminary assessment of the effect of food on the single dose Area Under the Curve (AUC) plasma concentrations of oxycodone derived from PF614 and oxycodone
  • 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
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of PF614 Compared to OxyContin® in Healthy Volunteers
Official Title  ICMJE 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®
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.
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Healthy
Intervention  ICMJE
  • Drug: PF614
    PF614 is an oxycodone prodrug
    Other Name: PRF06104
  • 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
Study Arms  ICMJE
  • 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.
    Interventions:
    • Drug: PF614
    • Drug: Naltrexone Hydrochloride
  • 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.
    Interventions:
    • Drug: Oxycodone extended-release
    • Drug: Naltrexone Hydrochloride
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: December 2, 2017)
64
Original Estimated Enrollment  ICMJE
 (submitted: May 22, 2015)
60
Actual Study Completion Date  ICMJE January 10, 2018
Actual Primary Completion Date January 8, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 50 Years   (Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02454712
Other Study ID Numbers  ICMJE PF614-101
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Ensysce Biosciences
Study Sponsor  ICMJE Ensysce Biosciences
Collaborators  ICMJE PRA Health Sciences
Investigators  ICMJE
Study Director: William K Schmidt, PhD Ensysce Biosciences
PRS Account Ensysce Biosciences
Verification Date July 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP