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PharmacokineticsPhase 1MPAR-101NCT05090280

Pharmacokinetics of Oxycodone and PF614 Co-Administered with Nafamostat (PF614-MPAR-101)

A Phase 1 study testing PF614 solution, Naltrexone Hydrochloride and Nafamostat Mesylate in people with Pharmacokinetics, run by Ensysce Biosciences at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 55 yearsHealthy volunteers can take part
Conditions the study is for
Pharmacokinetics
What is being tested?
PF614 solution, Naltrexone Hydrochloride and Nafamostat Mesylate
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
111 participants
Where
1 siteUnited States
Study dates
1 Dec 2021to 26 Apr 2023
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 55 years
  • All sexes
  • Healthy volunteers accepted
  • Adult

Who may be able to join

  • Healthy males or non-pregnant, non-lactating healthy females
  • Ages 18 to 55 years, inclusive, at time of signing informed consent
  • Body mass index of 18.0 to 32.0 kg/m2 as measured at screening or, if outside the range, considered not clinically significant by the investigator
  • Minimum weight of 50kg at screening
  • Must be willing and able to comply with all study requirements
  • Must be able to understand a written informed consent, which must be obtained prior to initiation of study procedures
  • Must agree to use an adequate method of contraception

Who cannot join

  • Subjects who have received any Investigational Medical Product (IMP) in a clinical research study within 5 half-lives or within 30 days prior to first dose
  • Subjects who are, or are immediate family members of, a study site or sponsor employee
  • Evidence of current SARS-CoV-2 infection
  • Subjects who have previously been administered IMP in this study
  • History of any drug or alcohol abuse in the past 2 years
  • Regular alcohol consumption in males >21 units per week and females >14 units per week
Show all 22Show fewer
  • A confirmed positive alcohol urine test at screening or admission
  • Current smokers and those who have smoked within the last 12 months. A confirmed positive urine cotinine test at screening or first admission
  • Current users of e-cigarettes and nicotine replacement products and those who have used these products within the last 12 months
  • Females of childbearing potential must have a negative serum pregnancy test at screening and negative urine pregnancy test at each admission
  • Females who are expected to have their menses during the dosing period
  • Male subjects with pregnant or lactating partners
  • Have poor venous access that limits phlebotomy
  • Clinically significant abnormal chemistry, hematology, coagulation, or urinalysis as judged by the investigator
  • Positive drugs of abuse test result
  • Positive hepatis B surface antigen, hepatitis C virus antibody or human immunodeficiency virus antibody results
  • History of clinically significant cardiovascular, renal, hepatic, chronic respiratory or GI disease, neurological or psychiatric disorder, as judged by the investigator
  • Subjects with a history of cholecystectomy or gall stones
  • Subjects with a history of seizures
  • Serious adverse reaction or serious hypersensitivity to any drug or the formulation excipients
  • Presence or history of clinically significant allergy requiring treatment, as judged by the investigator. Hay fever is allowed unless it is active
  • Donation of blood within 2 months or donation of plasma within 7 days prior to first dose of study medication -

Trial locations and contacts

1 site in 1 country.

United States1 site
  • Quotient Sciences

    Miami, Florida, 33126

Other trials in United States

About this study

Official title: A Single Dose Study to Evaluate the Pharmacokinetics of Oxycodone and PF614 When PF614 Solution is Co-Administered with Nafamostat, As an Immediate Release Solution And/or Extended Release (ER) Capsule Formulations in Healthy Subjects

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.

Read the 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.

Being tested
PF614 solution, Naltrexone Hydrochloride, Nafamostat Mesylate

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • PF614 solutionDrug

    Also called PRF06104, Oxycodone prodrug

    PF614 solution is an oxycodone prodrug

  • Naltrexone HydrochlorideDrug

    Also called ReVia

    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.

  • Nafamostat MesylateDrug

    Also called Futhan

    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.

Study groups in NCT05090280
Study groupRoleWhat they receive
PF614 solutionExperimentalCohort 1 and 6 will consist of 6 evaluable subjects. Subjects will receive the PF614 solution alone and concomitantly with nafamostat as an IR solution and/or ER prototype capsules. Subjects will receive naltrexone prior to and following each regimen. Cohorts 2 to 5 and Cohorts 7 to 10 will consist of 5 evaluable subjects in each cohort. Only 2 sentinel subjects will be dosed (one male and one female) in Period 2, Cohort 1. After review of the PK data and safety data, the safety advisory committee will decide the nafamostat dose level. After Cohorts 3 and 8 only: The fed vs fasted regimen will be determined for Cohorts 4 and 9.
Receives: Drug: PF614 solution; Drug: Naltrexone Hydrochloride
PF614 solution concomitantly with nafamostatExperimentalCohort 1 and 6 will consist of 6 evaluable subjects. Subjects will receive the PF614 solution alone and concomitantly with nafamostat as an IR solution and/or ER prototype capsules. Subjects will receive naltrexone prior to and following each regimen. Cohorts 2 to 5 and Cohorts 7 to 10 will consist of 5 evaluable subjects in each cohort. Only 2 sentinel subjects will be dosed (one male and one female) in Period 2, Cohort 1. After review of the PK data and safety data, the safety advisory committee will decide the nafamostat dose level. After Cohorts 3 and 8 only: The fed vs fasted regimen will be determined for Cohorts 4 and 9.
Receives: Drug: PF614 solution; Drug: Naltrexone Hydrochloride; Drug: Nafamostat Mesylate

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Pharmacokinetic Tmax [Time to Maximum Plasma Concentration]

    Time to maximum observed concentrations of oxycodone following administration of PF614 solution alone and with nafamostat

    Measured: pre-dose, 0.5,1,1.5,2,3,4,6,8,12,16,24,36,48 hours

  2. Pharmacokinetic Cmax [Maximum Plasma Concentration]

    Maximum (peak) observed concentration of oxycodone following administration of PF614 solution alone and with nafamostat

    Measured: pre-dose, 0.5,1,1.5,2,3,4,6,8,12,16,24,36,48 hours

  3. Pharmacokinetic C24 [Plasma concentration at 24 hours]

    Concentration of oxycodone at 24h post-dose following administration of PF614 solution alone and with nafamostat

    Measured: 24 hours

  4. Pharmacokinetic AUC [Area Under the Curve]

    Area under the concentration-time curve from time 0 to the time of last measurable concentrations of oxycodone following administration of PF614 solution alone and with nafamostat

    Measured: pre-dose, 0.5,1,1.5,2,3,4,6,8,12,16,24,36,48 hours

  5. Pharmacokinetic AUC(0-last)

    Area under the concentration-time curve from time 0 extrapolated to time-infinity of oxycodone following administration of PF614 solution alone and with nafamostat

    Measured: pre-dose, 0.5,1,1.5,2,3,4,6,8,12,16,24,36,48 hours

  6. Pharmacokinetic T1/2 [Half-life]

    Terminal elimination half-life concentrations of oxycodone following administration of PF614 solution alone and with nafamostat

    Measured: pre-dose, 0.5,1,1.5,2,3,4,6,8,12,16,24,36,48 hours

Secondary outcomes (4)
  1. Bioavailability Cmax

    Comparative evaluation of the bioavailability of oxycodone and PF614 based on Cmax when PF614 solution is co-administered with nafamostat in the fed state compared to the fasted state

    Measured: pre-dose, 0.5,1,1.5,2,3,4,6,8,12,16,24,36,48 hours

  2. Bioavailability AUC(0-last)

    Comparative evaluation of the bioavailability of oxycodone and PF614 based on AUC(0-last) when PF614 solution is co-administered with nafamostat in the fed state compared to the fasted state

    Measured: pre-dose, 0.5,1,1.5,2,3,4,6,8,12,16,24,36,48 hours

  3. Bioavailability AUC(0-inf)

    Comparative evaluation of the bioavailability of oxycodone and PF614 based on AUC(0-inf) when PF614 solution is co-administered with nafamostat in the fed state compared to the fasted state

    Measured: pre-dose, 0.5,1,1.5,2,3,4,6,8,12,16,24,36,48 hours

  4. Incidence of Treatment-Emergent Adverse Effects [Safety and Tolerability]

    Adverse events (AEs), Significant Adverse Events (SAEs), AEs leading to discontinuation

    Measured: 30 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted22 Oct 2021
  2. Study start1 Dec 2021
  3. Primary completion26 Apr 2023
  4. Study completion26 Apr 2023

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
111 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05090280
Sponsor's protocol ID
QSC203698
Other IDs
5UH3DA047682-04
Acronym
MPAR-101
Status last verified
Sep 2024
First submitted
28 Sep 2021
Last updated
24 Sep 2024
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 38511523
  • Kirkpatrick DL, Schmidt WK, Morales R, Cremin J, Seroogy J, Husfeld C, Jenkins T. In vitro and in vivo assessment of the abuse potential of PF614, a novel BIO-MD prodrug of oxycodone. J Opioid Manag. 2017 Jan/Feb;13(1):39-49. doi: 10.5055/jom.2017.0366.

    PubMed 28345745

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing PF614 solution, Naltrexone Hydrochloride and Nafamostat Mesylate in people with Pharmacokinetics, run by Ensysce Biosciences at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 24 Sep 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Pharmacokinetic Tmax [Time to Maximum Plasma Concentration] (time frame: pre-dose, 0.5,1,1.5,2,3,4,6,8,12,16,24,36,48 hours). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05090280, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Sep 2024.

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