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.

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.