Open-Label Safety and PK Study of ER Hydromorphone Tablets in Opioid-Tolerant Pediatric Chronic Pain Patients

An Open-Label, Safety and Pharmacokinetic Study of Hydromorphone Hydrochloride Extended-Release Tablets (Once-Daily Hydromorphone) in Opioid-Tolerant Pediatric Subjects With Chronic Pain

This pediatric study is designed to provide safety information, dosing guidelines, and a pharmacokinetic (PK) evaluation of once-daily hydromorphone hydrochloride (HCl) extended-release (ER) tablets in children with chronic painful conditions who are "opioid-tolerant" prior to enrollment under the Pediatric Research Equity Act (PREA) of 2003.

Study Overview

• Status: Terminated
• Conditions: Chronic Pain
• Intervention / Treatment: Drug: Hydromorphone HCl ER Tablets

• Study Type: Interventional
• Enrollment (Actual): 5
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Florida
    • Miami, Florida, United States, 33165
      • Medical Professional Clinical Research
    • Miami, Florida, United States, 33136
      • Jackson Memorial Hospital, University of Miami
    • Tampa, Florida, United States, 33617
      • Clinical Pharmacology Services, Inc.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 7 years to 17 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion:

1. Male or female subjects aged 7 to 17 years.
2. Chronic cancer or noncancer pain (requiring around-the-clock opioid treatment) currently managed with stable dose of oral or injectable opioid corresponding to at least 6 mg of hydromorphone per day for at least 5 days prior to first dose.
3. Female subjects of child bearing potential must have negative serum pregnancy test result at Screening and Day 1. If sexually active must be surgically sterilized at least 12 months prior to Screening or use contraception at least 30 days prior to Screening and for the duration of study participation and for at least 30 days after the last dose of study drug.
4. Male subjects, with reproductive potential, who are sexually active must agree to use an acceptable method of contraception for the duration of the study.
5. Opioid-tolerant.
6. Subjects must have established a favorable response to opioid therapy in reducing pain.
7. Subjects must require a minimum dose of 4 mg (1 JURNISTA tablet) and a maximum dose of 16 mg (1 EXALGO tablet) after determining 66% of the converted dose of hydromorphone HCl per day from an established conversion table.
8. Able to swallow a whole tablet without breaking, crushing, chewing or dissolving.
9. Expected to require extended opioid treatment for at least 1 week.
10. Subjects must be able to communicate effectively with study personnel.
11. Subjects and parents/legal guardian must be able and willing to follow all protocol requirements and study restrictions.

Exclusion:

1. Life expectancy of less than 4 weeks.
2. History of allergy or any significant intolerance with opioid treatment or allergies to sulfites.
3. Currently using opioid (transcutaneous) analgesic patches.
4. History of drug or alcohol dependence.
5. History of renal, hepatic, cardiovascular, or respiratory conditions that would contraindicate participation in this study.
6. Plan to undergo a surgical procedure within 3 days of Day 1 and for the duration of subject participation in the study. Subjects undergoing minor surgical procedures (eg, central line insertion, biopsies) will be eligible for participation in the study.
7. Exhibit hemodynamic instability.
8. Have dysphagia, or difficulty swallowing whole tablets.
9. Narrowing of the digestive tract, Short gut syndrome, inflammatory bowel disease, peritonitis, cystic fibrosis, Meckel's diverticulum, or past GI surgery.
10. Hypothyroidism, Addison's disease, asthma (including exercise induced asthma) requiring daily inhalers, an enlarged prostate, epilepsy, low blood pressure, seizure disorder, high intracranial brain pressure, gallbladder problems, pancreatic disease, liver disease, or kidney disease.
11. Ileostomy or paralytic ileus.
12. Blood-product transfusion within 2 weeks of enrollment or expected to require transfusion during study.
13. Participated in a study with an investigational drug or device in the past 30 days prior to screening.
14. Known history of human immunodeficiency virus (HIV), hepatitis C virus (HCV) or hepatitis B virus.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Hydromorphone HCl ER Tablets; Participants receive Hydromorphone HCl ER Tablets (4-16 mg, based on standard conversion ratios for common opioids)	Drug: Hydromorphone HCl ER Tablets; Hydromorphone hydrochloride (HCl) extended release tablet; Other Names: Exalgo, Jurnista

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Adverse Events (AEs)	Clinically significant changes in vital signs, pulse oximetry, and/or clinical laboratory assessments, were recorded as AEs	28 days

Collaborators and Investigators

• Sponsor: Mallinckrodt

Study record dates

Study Major Dates

• Study Start (Actual): March 11, 2017
• Primary Completion (Actual): February 4, 2019
• Study Completion (Actual): February 4, 2019

Study Registration Dates

• First Submitted: December 12, 2014
• First Submitted That Met QC Criteria: December 19, 2014
• First Posted (Estimate): December 22, 2014

Study Record Updates

• Last Update Posted (Actual): May 21, 2020
• Last Update Submitted That Met QC Criteria: May 20, 2020
• Last Verified: May 1, 2020

More Information

Terms related to this study

• Keywords: Pediatric
• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Chronic Pain; Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Opioid; Narcotics; Hydromorphone
• Other Study ID Numbers: COV02520124

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No