Chronic Pain
Conditions
Keywords
Hydromorphone Hydrochloride, Hydromorphone, Pain, Chronic Pain, Implantable Pump, Pump, Intrathecal
Brief summary
The purpose of this study is to evaluate the long-term safety of hydromorphone hydrochloride administered by intrathecal delivery.
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.
Interventions
Opioid for chronic pain
Device: Programmable Implantable pump Programmable Implantable pump delivering intrathecal hydromorphone
Sponsors
Piramal Critical Care, Ltd.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Granulomas | 12 months | Subjects with Clinical Signs and Symptoms of Granuloma \[Note: The primary endpoint of this trial is Safety. There is no formal efficacy assessment planned in this open-label safety study.\] |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Brief Pain Inventory (BPI) - Mean Pain Severity | Early Termination/Final Visit through 12 months | 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. |
| Patient Global Impression of Change (PGIC) | Early Termination/Final Visit through 12 months | 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. |
| Visual Analog Scale Pain Intensity (VASPI) | Early Termination/Final Visit through 12 months | 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. |
Countries
United States
Participant flow
Pre-assignment details
Protocol states, Approximately 350 subjects to be enrolled....... Additional subjects may be enrolled as deemed necessary to reach the study completion requirements for subjects on long term intrathecal hydromorphone hydrochloride therapy.
Participants by arm
| Arm | Count |
|---|---|
| Hydromorphone Hydrochloride Hydromorphone hydrochloride 0.1 mg/day to 10 mg/day based in dose titration, by intrathecal administration, 12 months safety evaluation
Hydromorphone Hydrochloride: Opioid for chronic pain
Programmable Implantable pump: Device: Programmable Implantable pump
Programmable Implantable pump delivering intrathecal hydromorphone | 364 |
| Total | 364 |
Baseline characteristics
| Characteristic | Hydromorphone Hydrochloride |
|---|---|
| Age, Continuous | 56.3 years STANDARD_DEVIATION 10.3 |
| Brief Pain Inventory (BPI) | 5.44 units on a scale STANDARD_DEVIATION 1.92 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 8 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 356 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Patient Global Impression of Change (PGIC) | 4.24 units on a scale STANDARD_DEVIATION 2.02 |
| Race/Ethnicity, Customized American Indian or Alaska Native | 4 participants |
| Race/Ethnicity, Customized Black or African American | 16 participants |
| Race/Ethnicity, Customized Multi-racial (no primary race) | 2 participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 1 participants |
| Race/Ethnicity, Customized Other | 3 participants |
| Race/Ethnicity, Customized White | 338 participants |
| Region of Enrollment United States | 364 Participants |
| Sex: Female, Male Female | 220 Participants |
| Sex: Female, Male Male | 144 Participants |
| Visual Analog Scale Pain Intensity (VASPI) | 48.16 mm STANDARD_DEVIATION 26.69 |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 7 / 364 |
| other Total, other adverse events | 308 / 364 |
| serious Total, serious adverse events | 71 / 364 |
Outcome results
Primary
Granulomas
Subjects with Clinical Signs and Symptoms of Granuloma \[Note: The primary endpoint of this trial is Safety. There is no formal efficacy assessment planned in this open-label safety study.\]
Time frame: 12 months
Population: All Enrolled Subjects
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Hydromorphone Hydrochloride | Granulomas | Subjects without Clinical Signs and Symptoms of Granuloma | 352 Participants |
| Hydromorphone Hydrochloride | Granulomas | MRI Confirms Granuloma | 0 Participants |
| Hydromorphone Hydrochloride | Granulomas | Subjects with Clinical Signs and Symptoms of Granuloma | 12 Participants |
| Hydromorphone Hydrochloride | Granulomas | Investigator Considers Signs and Symptoms to be Caused by Granuloma | 0 Participants |
Secondary
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.
Time frame: Early Termination/Final Visit through 12 months
Population: ITT (Intent to Treat) with non-missing Baseline and Early Termination/Final Visit assessment for computing change from baseline
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Hydromorphone Hydrochloride | Brief Pain Inventory (BPI) - Mean Pain Severity | -.20 units on a scale | Standard Deviation 1.8 |
Secondary
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.
Time frame: Early Termination/Final Visit through 12 months
Population: ITT (Intent to Treat) with non-missing Baseline and Final Visit assessment for computing change from baseline
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Hydromorphone Hydrochloride | Patient Global Impression of Change (PGIC) | 0.44 units on a scale | Standard Deviation 2.13 |
Secondary
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.
Time frame: Early Termination/Final Visit through 12 months
Population: ITT (Intent to Treat) with non-missing Baseline and Final Visit assessment for computing change from baseline
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Hydromorphone Hydrochloride | Visual Analog Scale Pain Intensity (VASPI) | -0.41 mm | Standard Deviation 26.1 |