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

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

Detailed Description
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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.

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

Conditions
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Chronic Pain

Intervention / Treatment
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* Drug: Hydromorphone Hydrochloride
* Device: Programmable Implantable pump


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects must meet all of the following criteria to be included: Subjects must be at least 18 years of age and no more than 75 years old. Clinically diagnosed with severe chronic pain for at least a 6-month period. 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. Subject agrees to sign a Pain Treatment Agreement (Narcotic Contract) limiting narcotic prescriptions to the study medication prescribed by the investigator. Subject must be cognitively intact and, in the opinion of the investigator, capable of participation in the trial. Female subjects of child-bearing potential must agree to use a medically acceptable and effective double-barrier method of birth control. Subjects who can receive an MRI if required by the study protocol. Provides written Ethics Committee approved informed consent. Willing to comply with all study procedures and requirements. Exclusion Criteria: Subjects meeting any of the following criteria will be excluded: Women who are pregnant or breast-feeding. Subject has any known or suspected allergy to hydromorphone hydrochloride or to the materials of the infusion pump or intrathecal catheter. 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). Subjects who show signs of active systemic infection. Subjects with a metastatic cancer to the spinal canal or a known central nervous system contraindication to intrathecal therapy. Subjects have a condition requiring diathermy procedures. Subject has a life expectancy of less than 12 months. Subjects who are unable or unwilling to return to all of the required follow-up visits. As a result of medical review and physical examination, the Investigator considers the subject unfit for the study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Hydromorphone Hydrochloride<br>Hydromorphone hydrochloride for intrathecal administration, 12 months safety evaluation | Drug: Hydromorphone Hydrochloride<br>* Opioid for chronic pain<br>* Other names: Opioid;Device: Programmable Implantable pump<br>* Device: Programmable Implantable pump Programmable Implantable pump delivering intrathecal hydromorphone<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hydromorphone Hydrochloride, Hydromorphone, Pain, Chronic Pain, Implantable Pump, Pump, Intrathecal