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

NCT02687451 | Terminated Phase 3 Results DMC

• 1 other identifier: EN3319-304
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 3

Brief Summary

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.

Conditions

Post-Operative Pain; Acute Pain

Keywords

Surgical Pain; Acute Post-Surgical Pain

Outcome Measures

Primary Outcomes (2)

• Cumulative Total Amount of Morphine Rescue Medication Required for Analgesia in the Active Treatment Group (Single Dose)

  Up to 24 hours post dose

• Cumulative Total Amount of Morphine Rescue Medication Required for Analgesia in the Active Treatment Group Versus Placebo Group (Multiple Dose).

  Up to 24 hours post dose

Secondary Outcomes (3)

• Assessment of Pain Using the Age Appropriate Scale, Face, Legs, Activity, Cry, Consolability (FLACC) or the Neonatal Infant Pain Scale (NIPS).

  Single Dose Phase: at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6 and 8 hours post dose. Multiple Dose Phase: every 0.5 hours up to 24 hours post first dose.

• Pharmacokinetic Variable: Volume of Distribution (Vd)

  Single Dose Phase: at 0 (Baseline), 0.5, 1.0, 2.0, 3.0, 4.0, 8.0, and 24 hours post dose. Multiple Dose Phase: Baseline before each dose only

• Pharmacokinetic Variable: Clearance (CL)

  Single Dose Phase: at 0 (Baseline), 0.5, 1.0, 2.0, 3.0, 4.0, 8.0, and 24 hours post dose. Multiple Dose Phase: Baseline before each dose

Study Arms (3)

Oxymorphone HCl Open-Label Phase

EXPERIMENTAL

Oxymorphone HCl Immediate Release Oral Liquid and Oxymorphone HCl Injection; open-label, single-dose, dose selection phase.

Drug: Oxymorphone HCl

Oxymorphone HCl Multiple-Dose Phase

EXPERIMENTAL

Oxymorphone HCl Immediate Release Oral Liquid and Oxymorphone HCl Injection; placebo controlled, randomized, double-blinded multiple-dose phase.

Drug: Oxymorphone HCl

Placebo

PLACEBO COMPARATOR

Sodium Chloride 0.9% solution; comparator for multiple-dose phase.

Drug: Placebo

Interventions

Oxymorphone HCl DRUG

Oral liquid and injection; dose to be determined by Independent Data Monitoring Committee (IDMC).

Also known as: Opana

Oxymorphone HCl Multiple-Dose Phase; Oxymorphone HCl Open-Label Phase

Placebo DRUG

Placebo Comparator for the double-blinded, placebo-controlled multiple-dose phase.

Placebo

Eligibility Criteria

• Age: 0 Years - 2 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Is male or female \<2 years of age at the time of surgery.
• Must weigh at least 3 kg.
• 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.
• 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.
• The subject's parent or guardian has been informed of the nature of the study and has provided written informed consent.
• Postoperative:
• 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).
• Is an inpatient expected to be hospitalized for 24 hours after dosing with study drug.
• Has an indwelling access catheter for blood sampling.
• 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.
• 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.

You may not qualify if:

• Subjects who meet any of the following criteria will not be eligible to participate in the study:
• 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.
• Has any clinical laboratory test result outside the accepted range that has been confirmed upon re-examination and deemed to be clinically significant.
• Has a clinically significant illness or condition any time before dosing with study drug that would contraindicate participation, as determined by the Investigator.
• Has a life expectancy \<8 weeks.
• For age groups A and B: Has a malabsorption, gastroenterologic, or abdominal condition that would interfere with the absorption of study drug.
• Has evidence of increased intracranial pressure.
• 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%.
• Has a history of seizures.
• 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.
• Subject (and/or mother if subject is nursing) has received preoperative opioids for more than 72 consecutive hours.
• Subject (and/or mother if subject is nursing) has received oxycodone or oxymorphone within 48 hours prior to screening.
• 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.
• 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.
• Parent or legal guardian is unable to provide consent for any reason (eg, mental or physical disabilities, language barriers, or is unavailable).

Sponsors & Collaborators

• Endo Pharmaceuticals: lead

Study Sites (3)

Endo Clinical Trial Site #2

Durham, North Carolina, 27710, United States

Location

Endo Clinical Trial Site #1

Dallas, Texas, 75235, United States

Location

Endo Clinical Trial Site #4

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Pain, Postoperative; Acute Pain

Interventions

Oxymorphone

Condition Hierarchy (Ancestors)

Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Pain; Neurologic Manifestations; Signs and Symptoms

Intervention Hierarchy (Ancestors)

Morphine Derivatives; Morphinans; Opiate Alkaloids; Alkaloids; Heterocyclic Compounds; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds

Results Point of Contact

• Title: Saji Vijayan, MBBS
• Organization: Endo Pharmaceuticals

clinicaltrials@endo.com

800-462-3636

Study Officials

• Shannon Dalton

  Endo Pharmceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 14, 2016
• First Posted: February 22, 2016
• Study Start: April 1, 2016
• Primary Completion: July 1, 2020
• Study Completion: September 15, 2020
• Last Updated: October 26, 2021
• Results First Posted: October 26, 2021

Record last verified: 2021-01

Locations

US (3)