Single-arm Study to Assess the Safety of Hydromorphone Hydrochloride by Intrathecal Administration

A Phase 3, Open-Label, Single-Arm Study To Assess The Safety Of Hydromorphone Hydrochloride Delivered By Intrathecal Administration

The purpose of this study is to evaluate the long-term safety of hydromorphone hydrochloride administered by intrathecal delivery.

Study Overview

• Status: Completed
• Conditions: Chronic Pain
• Intervention / Treatment: Drug: Hydromorphone Hydrochloride; Device: Programmable Implantable pump

Detailed Description

This is an open-label, single-arm safety study to evaluate the safety of hydromorphone hydrochloride given by continuous intrathecal infusion using an implantable pump device. This study will enroll both subjects on a current opioid intrathecal medication as well as naïve subjects now current on intrathecal opioid medications. All subjects currently on intrathecal opioid treatment will be converted from their current intrathecal therapy to intrathecal hydromorphone hydrochloride according to standard medical practice. After an optimal dose for pain relief is achieved, subjects will remain on therapy for a total of 12 months or until discontinuation from the study. During this continuous dosing period, dose adjustments (up or down) are permitted to manage pain or side effects provided a maximum dose of 10 mg/day is not exceeded. Subjects will be assessed for pain intensity using a visual analog scale of pain intensity (VASPI) instrument at each study visit.

Subjects will be evaluated for side effects and clinical complications associated with the use of intrathecal hydromorphone. Events will be classified by intrathecal drugs used and concentrations.

• Study Type: Interventional
• Enrollment (Actual): 364
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27103
      • The Center for Clinical Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Subjects must meet all of the following criteria to be included:

1. Subjects must be at least 18 years of age and no more than 75 years old.
2. Clinically diagnosed with severe chronic pain for at least a 6-month period.
3. Subject is reasonably expected to benefit from intrathecal pain medication and has a programmable implantable intrathecal pump or meets clinical criteria for implantation of an intrathecal pump per Standard of Care.
4. Subject agrees to sign a Pain Treatment Agreement (Narcotic Contract) limiting narcotic prescriptions to the study medication prescribed by the investigator.
5. Subject must be cognitively intact and, in the opinion of the investigator, capable of participation in the trial.
6. Female subjects of child-bearing potential must agree to use a medically acceptable and effective double-barrier method of birth control.
7. Subjects who can receive an MRI if required by the study protocol.
8. Provides written Ethics Committee approved informed consent.
9. Willing to comply with all study procedures and requirements.

Exclusion Criteria:

Subjects meeting any of the following criteria will be excluded:

1. Women who are pregnant or breast-feeding.
2. Subject has any known or suspected allergy to hydromorphone hydrochloride or to the materials of the infusion pump or intrathecal catheter.
3. Subject has a history of dependence and abuse of opioids, stimulants, alcohol, or benzodiazepines, as defined by Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) criteria, within the past year (physical dependence on prescribed opioid analgesics is allowed but abuse of opioids according to DSM-IV is not permitted, i.e. opioid addiction for recreational use).
4. Subjects who show signs of active systemic infection.
5. Subjects with a metastatic cancer to the spinal canal or a known central nervous system contraindication to intrathecal therapy.
6. Subjects have a condition requiring diathermy procedures.
7. Subject has a life expectancy of less than 12 months.
8. Subjects who are unable or unwilling to return to all of the required follow-up visits.
9. As a result of medical review and physical examination, the Investigator considers the subject unfit for the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Hydromorphone Hydrochloride; Hydromorphone hydrochloride for intrathecal administration, 12 months safety evaluation	Drug: Hydromorphone Hydrochloride; Opioid for chronic pain; Other Names: Hydromorphone; Opioid; Device: Programmable Implantable pump; Device: Programmable Implantable pump Programmable Implantable pump delivering intrathecal hydromorphone

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Granulomas	Subjects with Clinical Signs and Symptoms of Granuloma [Note: The primary endpoint of this trial is Safety. There is no formal efficacy assessment planned in this open-label safety study.]	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Brief Pain Inventory (BPI) - Mean Pain Severity	Change from Baseline in the Brief Pain Inventory (BPI). Pain Severity Measures, Scale: 0 = No Pain, 10 = Pain as bad as you can imagine; a high score indicates a worse outcome. Therefore, a negative change from baseline indicates a better outcome. Outcome is Mean Pain Severity score calculated as the arithmetic mean of the Worst, Least, Average and Now scores. A negative change indicates better outcome.	Early Termination/Final Visit through 12 months
Patient Global Impression of Change (PGIC)	Change from Baseline in the Patient Global Impression of Change (PGIC). Scale: 7-point Likert scale, from 1 = No Change through 7 = A great deal better; a high score indicates a better outcome. Therefore, a positive change from baseline indicates a better outcome.	Early Termination/Final Visit through 12 months
Visual Analog Scale Pain Intensity (VASPI)	Change from Baseline in Visual Analog Scale Pain Intensity (VASPI). Scale: 0 mm = No Pain, 100 mm = Unbearable Pain; high score is worse. Therefore, a negative change from baseline indicates a better outcome.	Early Termination/Final Visit through 12 months

Collaborators and Investigators

• Sponsor: Piramal Critical Care, Ltd.
• Investigators: Principal Investigator: Richard Rauck, MD, Carolinas Pain Institute

Study record dates

Study Major Dates

• Study Start (ACTUAL): June 1, 2013
• Primary Completion (ACTUAL): February 1, 2018
• Study Completion (ACTUAL): February 1, 2018

Study Registration Dates

• First Submitted: September 4, 2012
• First Submitted That Met QC Criteria: October 17, 2012
• First Posted (ESTIMATE): October 18, 2012

Study Record Updates

• Last Update Posted (ACTUAL): August 25, 2021
• Last Update Submitted That Met QC Criteria: August 23, 2021
• Last Verified: August 1, 2021

More Information

Terms related to this study

• Keywords: Pain; Chronic Pain; Hydromorphone; Implantable Pump; Pump; Intrathecal; Hydromorphone Hydrochloride
• 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: CNS-HYD202US

Plan for Individual participant data (IPD)

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