| Eligibility |
Inclusion Criteria:
1. Male or female subjects 18 to 55 years of age, inclusive.
2. Subjects are in good health as indicated by medical history, PE, vital signs, oxygen
saturation, clinical laboratory tests, and 12-lead ECG. A status of good health will
be defined by the absence of evidence of any clinically significant, active or chronic
disease based on these assessments, in the opinion of the investigator.
3. Subjects with a body mass index (BMI) of 18.0 to 33.0 kg/m2, inclusive, and body
weight greater than 50 kg, inclusive.
4. Subject is able to speak, read, and understand English and voluntarily provide written
informed consent to participate in the study.
5. Subjects have healthy oral mucosa as determined by examination at screening and
admission to the clinical facility.
6. Subject must be a recreational opioid user who is not currently dependent on opioids
(based on self-reported DSM-5 criteria and a Clinical Opiate Withdrawal Scale [COWS]
score =5 on the Naloxone Challenge) but has experience in the use of opioids for
non-therapeutic purposes (ie, for psychoactive effects) on at least 10 occasions
within the last year and at least once in the 12 weeks prior to the screening visit.
7. Subject demonstrates adequate VRH at screening during VRH assessment, defined as a
minimum increase in ETCO2 of 10 mmHg and an increase in minute ventilation appropriate
per investigator's discretion.
8. Ability and willingness to abstain from alcohol-, caffeine-, and xanthine-containing
beverages or food (eg, coffee, tea, cola, chocolate, energy drinks) as well as poppy
seeds from 48 hours (2 days) prior to each admission to the clinical facility until
study discharge (including clinic furloughs).
9. Female subjects who are non-pregnant, non-lactating, and either postmenopausal for at
least 1 year or surgically sterile for at least 3 months, or, if of childbearing
potential, will agree to use adequate contraception from 28 days and/or their last
confirmed menstrual period prior to study enrollment (whichever is longer) until 90
days after the follow-up visit. Male subjects, if not surgically sterilized, must
agree to use adequate contraception and not donate sperm from first admission to the
clinical research center until 90 days after the follow-up visit. Adequate
contraception (for both males and females) is defined as using spermicide with a
single barrier method: diaphragm, cervical cap, or condom. For female participants and
female partners of male participants, being surgically sterilized or using hormonal
contraception or an intrauterine device is also acceptable. Also, total abstinence, in
accordance with the lifestyle of the subject, is acceptable.
10. For female subjects: a negative pregnancy test at screening and Day -1 of each
treatment period.
11. Postmenopausal females: defined as 12 months with no menses prior to screening and a
serum follicle stimulating hormone (FSH) >40 IU/L at screening.
12. All prescribed medications, over-the-counter (OTC) medications, dietary supplements or
herbal supplements (eg, St. John's Wort extract) must have been stopped at least 14
days prior to the first admission to the clinical research center. An exception is
made for acetaminophen, which is allowed up to admission to the clinical research
center. An exception is also made for hormonal contraceptives, which may be used
throughout the study. Antiemetics may be allowed after the 4-hour VRH assessments
while confined in the clinical research unit.
Exclusion Criteria:
1. Employee of PRA or the Sponsor.
2. Women who are pregnant, lactating, or planning to attempt to become pregnant during
this study or within 90 days after the follow-up visit.
3. Male subjects with female partners who are pregnant, lactating, or planning to attempt
to become pregnant during this study or within 90 days after the follow-up visit.
4. Has received study medication in another clinical trial within 30 days prior to the
first dose of study medication.
5. Having any disease that, in the opinion of the investigator, poses an unacceptable
risk to the subjects.
6. History of drug allergy diagnosed by a physician. Confirmatory circumstances would
include treatment with epinephrine or an Emergency Department.
7. Subjects who have smoked on a daily basis within 30 days prior to the first dose of
study medication. Occasional nicotine use in the form of cigarettes, cigars, or vape
pen is allowable (defined as less than half a pack of cigarettes [10 cigarettes],
equivalent vaping [100 puffs], or no more than 2 cigars per week). Nicotine
replacement therapies (ie, patches and/or gum) may be used without restriction.
8. Routine or chronic use of more than 3 grams of acetaminophen daily.
9. Strenuous activity and contact sports within 48 hours (2 days) prior to first
admission to the clinical facility and for the duration of the study.
10. History of donation of more than 450 mL of blood within 60 days prior to dosing in the
clinical research center or planned donation before 30 days has elapsed since intake
of study drug.
11. Plasma or platelet donation within 7 days of first dose administration and throughout
the entire study.
12. History of or presence of alcohol dependence. This includes subjects who have never
been to a drug rehabilitation program. Alcohol consumption will be prohibited 48 hours
prior to admission to the clinical facility and throughout the entire study until
discharge.
13. Positive screening test for hepatitis B surface antigen (HBsAg), anti-hepatitis C
virus (HCV) antibodies, or antihuman immunodeficiency virus (HIV)-1 and -2 antibodies.
14. History or presence of clinically significant cardiovascular, pulmonary, hepatic,
renal, hematologic, gastrointestinal, endocrine, immunologic, dermatologic,
neurologic, oncologic, or psychiatric disease, or any other condition, which, in the
opinion of the investigator, would jeopardize the safety of the subject or the
validity of the study results.
15. Has any condition in which an opioid is contraindicated (eg, significant respiratory
depression, acute or severe bronchial asthma or hypercarbia, or has or is suspected of
having paralytic ileus).
16. Have a history of chronic obstructive pulmonary disease or any other lung disease (eg,
asthma, bronchitis, obstructive sleep apnea, exercise-induced asthma) that would cause
CO2 retention.
17. Has participated in (within the last 5 years), is currently participating in, or is
seeking treatment for substance-related disorders (excluding nicotine and caffeine).
18. A positive result for drugs of abuse (amphetamines, methamphetamines, barbiturates,
benzodiazepines, cocaine, and opioids, including oxycodone) at screening is acceptable
as long as the urine drug screen is negative for these drugs at admission to the
clinical facility. A positive test for THC is not exclusionary at screening or at
admission to the clinical facility. If a subject has a positive urine drug screen
(except THC) upon admission to the clinic (V3-V7) the subject will be dismissed from
the clinic and will be allowed to return at a later date (+14 days) to participate in
the missed treatment period. A subject may only test positive once (except THC) and be
allowed to return.
19. Has oral sores, mucositis, or inflammation in oral cavity at screening and check-in.
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