Study of PF614 Compared to OxyContin® in Healthy Volunteers

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.

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.