Microdose Pharmacokinetic Study of PRX-P4-003 In Healthy Volunteers

Study Overview
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Brief Summary
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The goal of the present study is to confirm in humans the in-vivo bioconversion of a Prodrug (PRX-P4-003) to (-)-fencamfamine (FCF) the active moiety when orally administered as a single microdose. A second component of the study will evaluate effect of food on pharmacokinetics of PRX-P4-003.

Detailed Description
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A crossover study comparing blood concentrations after oral administration of microdoses of (-)-fencamfamine (FCF; 40 µg) or its prodrug form (PRX-P4-003; 100 µg)) in the fasted state will be carried out in 4 healthy male volunteers (Study A). This will be followed by determination of blood concentrations of (-)-fencamfamine in a separate cohort of 4 volunteers following oral administration of a microdose of PRX-P4-003 (100 µg) in a fed state (Study B).

Official Title
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A Phase 0, Open-Label, Crossover Microdose Pharmacokinetic Study of PRX-P4-003 In Healthy Volunteers

Conditions
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Healthy Volunteers

Intervention / Treatment
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* Drug: PRX-P4-003, (-)-FCF


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male aged 18 to 45 years. Willing to fast for at least 8 hours overnight and 4 hours after study drug dose (Study A). BMI within 18 - 32 kg/m2, inclusive. Willing/able to provide signed Informed Consent Form & HIPAA authorization for this study. Agreement to use a highly effective method of birth control with partners of childbearing potential during the study and for 1 month after study dosing such as, abstinence, barrier methods. Normal heart rate (50 to 100 bpm) and blood pressure (diastolic 60-85 mm Hg and systolic 90 to 130 mm Hg, inclusive) at Screening and Day 0. Nonsmoker or has not smoked within the past 6 months of Screening Visit 1 and throughout study participation. Use of recreational and/or medicinal marijuana are NOT permitted within 3 months prior to Screening and during the study. Marijuana use should not be initiated after Screening. Able to communicate well with the Investigator and to comply with the study procedures, requirements, restrictions, and directions of the clinic staff. Exclusion Criteria: Main Criteria for Exclusion: Subjects who meet the following criteria are excluded from study participation History or presence of clinically significant respiratory, GI, renal, hepatic, hematological, neurological (including history of seizure), cardiovascular, psychiatric (including known addictive disorders), musculoskeletal, genitourinary, immunological, or dermatological disorders. The existence of any surgical or medical condition that, in the judgment of the clinical Investigator, might jeopardize the subject's safety, tolerability or interfere with the absorption, distribution, metabolism or excretion of the study drug. Any history of suicide attempts or current suicidal ideation. Abnormal clinically significant laboratory, physical, or neurological findings during screening. Abnormal and clinically significant ECG (as determined by the Investigator or his/her designee) at Screening or Day -0. Abnormalities include, but are not limited to, QTc interval (average of three ECGs) greater than or equal to 450 msec based on 12 lead ECG at Screening or Day -1. Subjects with a history of congenitally prolonged QT interval. In the 14 days (or 5 half-lives, whichever is longer) prior to dosing, the need for prescription medications. Use of acetaminophen greater than a single dose of 1000 mg up to 3 days prior to Day 1. Use of any investigational drug or medical device within 3 months prior to study admission. Known hypersensitivity to, or intolerance of, drugs with the same mechanism of action as PRX-P4-003 or (-)-fencamfamine. Donation or loss of greater than 500 mL of blood in the 8 weeks before dosing. or planned donation of blood at any time during trial participation. History of alcohol abuse (defined as regular or daily consumption of more than 4 alcoholic drinks per day) or drug addiction within the past 2 years, as determined by the Investigator. A positive urine drug, or positive alcohol urine (or breath) test at Screening or Day-1. Unwillingness to refrain from alcohol, or illicit or recreational drugs, within 24 hours prior to Day -1and during inpatient period. Seropositive for Hepatitis B, Hepatitis C, (tested during screening) or known HIV infection. The subject is unwilling or unable to comply with the protocol or scheduled appointments. The subject is unable to understand verbal or written English or any other language for which a certified translation of the approved informed consent is available.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: In the first arm a fixed order crossover of a PRX-P4-003 followed by administration of the (-)-FCF after a washout period. In the second arm a separate cohort will be administered PRX-P4-003 under fed conditions.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Crossover (fasted)<br>On Day 1 subjects are dosed with 100 µg of PRX-P4-003 and PK samples are drawn according to protocol, on Day 15 subjects are dosed with 40 µg of (-)-FCF. Both treatment will be administered under the fasted conditions. | Drug: PRX-P4-003, (-)-FCF<br>* sequential study<br>* Other names: Stimulant;|
| Experimental: Single Group (fed)<br>On Day 1 subjects are dosed with 100 µg of PRX-P4-003 and PK samples are drawn according to protocol. The treatment will be administered under the fed condition. | Drug: PRX-P4-003, (-)-FCF<br>* sequential study<br>* Other names: Stimulant;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Outcome | Plasma (-)-FCF exposure (AUC 0-t) after Oral dosing of PRX-P4-003 and (-)-FCF | 24 hours |