Clinical Study to Evaluate the Effectiveness, Safety, and Tolerability of Oxymorphone Immediate Release (IR) Oral Liquid in Post Surgical Pediatric Subjects

An Open-Label Single-Dose And Randomized, Double-Blind, Placebo-Controlled Multiple-Dose Study To Evaluate The Efficacy, Safety, Tolerability, And Pharmacokinetics Of Oxymorphone Hydrochloride (HCl) For Acute Moderate To Severe Postoperative Pain In Pediatric Subjects

The purpose of the study is to evaluate the efficacy, tolerability, safety and pharmacokinetics of Oxymorphone HCl as an analgesic for acute moderate to severe post-operative pain in pediatric subjects.

Inclusion Criteria:

1. Is male or female <2 years of age at the time of surgery.

2. Must weigh at least 3 kg.

3. Is scheduled to have a surgical procedure for which opioid analgesia will be needed to manage postoperative pain for at least 18 hours following intraoperative and/or postoperative IV analgesia.

4. Is generally healthy as documented by medical history; physical examination (including, but not limited to, the cardiovascular, gastrointestinal, respiratory, and central nervous systems); vital sign assessments; 12-lead electrocardiograms (EKGs); clinical laboratory assessments; and general observations. Any abnormalities or deviations from the acceptable range that might be considered clinically relevant by the study physician or investigator will be evaluated on a case-by-case basis, agreed upon by the Principal Investigator (or sub-investigator), and documented in study files before enrolling the subject in the study.

5. The subject's parent or guardian has been informed of the nature of the study and has provided written informed consent.

   Postoperative:

6. Is anticipated to require an analgesic regimen using a short-acting opioid (non-oxycodone or non-oxymorphone) analgesic after surgery (according to standard of care (SOC) as defined in the protocol).

7. Is an inpatient expected to be hospitalized for 24 hours after dosing with study drug.

8. Has an indwelling access catheter for blood sampling.

9. For Groups A and B: Has demonstrated signs of tolerating oral intake. All infants and children should be able to demonstrate strong suck and swallow reflexes and neurologic alertness and stability sufficient to handle oral secretions.

10. Prior to administration of oxymorphone HCl oral solution, for Groups A and B, had demonstrated the ability to tolerate clear liquids, following surgery according to the SOC at each institution. All infants and children should be able to demonstrate strong suck and swallow reflexes and neurologic alertness and stability sufficient to handle oral secretions. The ability to tolerate small amounts (1 to 2 oz.) of clear liquids without emesis (over 30 to 60 minutes) would support readiness for study participation and oral intake once the physician has ordered the diet advanced to clear liquids and the subject has ingested fluids by mouth without nausea or vomiting.

Exclusion Criteria:

Subjects who meet any of the following criteria will not be eligible to participate in the study:

1. Has the presence or history of a clinically significant disorder involving the cardiovascular, respiratory, renal, gastrointestinal, immunologic, hematologic, endocrine, or nervous system(s) or psychiatric disease that would contraindicate participation, as determined by the Investigator.
2. Has any clinical laboratory test result outside the accepted range that has been confirmed upon re-examination and deemed to be clinically significant.
3. Has a clinically significant illness or condition any time before dosing with study drug that would contraindicate participation, as determined by the Investigator.
4. Has a life expectancy <8 weeks.
5. For age groups A and B: Has a malabsorption, gastroenterologic, or abdominal condition that would interfere with the absorption of study drug.
6. Has evidence of increased intracranial pressure.
7. Has a respiratory condition requiring intubation or resulting in active bronchiolitis, asthma, stridor, or difficulty breathing due to congestion and increased nasal secretions, including oxygen (O2) saturation ≤92%.
8. Has a history of seizures.
9. Subject (and/or mother if subject is nursing) has used medications with actions characteristic of monoamine oxidase inhibitors (MAOIs) within 14 days before the start of the study drug is prohibited. Standard daily pediatric multivitamins may be taken until enrollment into the study but will be restricted during the study.
10. Subject (and/or mother if subject is nursing) has received preoperative opioids for more than 72 consecutive hours.
11. Subject (and/or mother if subject is nursing) has received oxycodone or oxymorphone within 48 hours prior to screening.
12. Subject (and/or mother if subject is nursing) has ingested caffeine- or xanthine-containing products (eg, theophylline) within 48 prior to screening. These products are also prohibited during periods when blood samples are collected.
13. Has a history of relevant drug allergies, food allergies, or both (ie, allergy to oxymorphone or other opioid analgesics) that could interfere with the study.
14. Parent or legal guardian is unable to provide consent for any reason (eg, mental or physical disabilities, language barriers, or is unavailable).
15. Subject (and/or mother if subject is nursing) has participated in a clinical study of an unapproved drug within the previous 30 days.
16. Is not suitable for entry into the study in the opinion of the Investigator.