Management of Chronic Pain
Conditions
Keywords
Hydromorphone, Hydromorphone Hydrochloride, Pain Management, Non-narcotic analgesics
Brief summary
The purpose of this study is to determine the safety and efficacy of hydromorphone hydrochloride by intrathecal administration using a programmable implantable pump.
Detailed description
A Controlled, Two-Arm, Parallel Group, Randomized Withdrawal Study to Assess the Safety and Efficacy of Hydromorphone Hydrochloride Delivered by Intrathecal Administration Using a Programmable Implantable Pump
Interventions
Opioid for chronic pain
Programmable Implantable pump delivering intrathecal hydromorphone
Sponsors
Piramal Critical Care, Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
DOUBLE (Subject, Investigator)
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. Subject must be at least 18 years of age and no more than 75 years old. 2. Clinically diagnosed with chronic pain for at least a 6-month period. 3. Subject is presently on intrathecal pain medication and has a SynchroMed II Implantable pump or meets clinical criteria for implantation of a SynchroMed II Implantable pump. Subjects who are naïve to intrathecal therapy, may be enrolled 2-weeks after pump implantation. 4. Subject agrees to sign a Pain Treatment Agreement (Narcotic Contract) limiting narcotic prescriptions to the study physician. 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 with existing SynchroMed II Implantable pumps and are reasonably expected to benefit from intrathecal opioid therapy only. 8. Subjects who are capable of receiving an MRI with or without contrast or CT myelogram, if required by the study protocol. 9. Provides written Ethics Committee approved informed consent. 10. 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 are breast-feeding 2. Subjects who have participated in an investigational drug or device trial within 4 weeks prior to enrollment. 3. Subject has any known or suspected allergy to hydromorphone or to the materials of the infusion pump or intrathecal catheter. 4. Subject is scheduled for a pump or catheter replacement within 6 months of their enrollment into the trial. 5. Subject has a history of dependence and abuse of opioids, stimulants, alcohol, or benzodiazepines, as defined by 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). 6. Subjects who show signs of active systemic infection. 7. Subjects with a metastatic cancer to the spinal canal or a known central nervous system contraindication to intrathecal therapy. 8. Subject has a condition requiring diathermy procedures. 9. Subject has a life expectancy of less than 12 months. 10. Subject cannot independently comprehend and participate in the required assessments, including responding to the VASPI, Short-form McGill Pain Questionnaire (SF-MPQ), Clinical Opiate Withdrawal Scale (COWS), Subjective Opiate Withdrawal Scale (SOWS), BPI and patient global impression of change (PGIC) measurement tools. 11. Subject is not considered to be medically or psychologically appropriate for pump implantation. 12. Subjects who are unable or unwilling to return to all of the required follow-up visits. 13. Subjects with active implanted devices such as pacemakers, defibrillators, and cochlear implants or other medical device use, if in the opinion of the investigator the device would interfere with the ability to perform an MRI or CT myelogram. 14. As a result of medical review and physical examination, the Investigator considers the subject unfit for the study. 15. Pain located above the shoulders in the head or neck region (e.g. trigeminal neuralgia), central pain syndromes or any other condition in which it is judged to be unlikely that the subject would benefit from intrathecal administration of the drug product. 16. Subjects who have previously been unresponsive to intrathecal hydromorphone therapy.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Subjects Who Are Treatment Failures During the Double-blind Randomized Withdrawal Period | 5 weeks [Baseline (Day 84) to Day 119 Visit] | Treatment failure during the Randomized Phase is defined as at least one of the following: a) increase of \>= 20mm VASPI vs. baseline over 5 days; b) intolerable pain that in investigator's opinion requires intervention; or c) pain-related interventions that violate protocol from Day 84 to Day 119. Note: Baseline pain for the randomized phase is defined as the average of the last 5 days with daily pain measurements while on an optimal intrathecal dose of Hydromorphone, between Days 77 and 83 of the open label dosing period. Note: A subject who does not have sufficient data for evaluation, drops out for any other reasons that are not listed above or who experiences withdrawal syndrome as identified by COWS \> 12 during the randomized phase will not be classified as a treatment failure. Note: Analysis period is from beginning of randomization phase (Day 84) to end of study. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Brief Pain Inventory (BPI): Pain Severity Average | 5 Weeks [Baseline (Day 84) to Day 119] | 'Average' pain experienced in the past 24 hours. The Brief Pain Inventory (BPI): Scale: 0 = No Pain, 10 = Pain as bad as you can imagine; a high score indicates a worse outcome. |
| Brief Pain Inventory (BPI): Pain Severity Summary Measure | 5 Weeks [Baseline (Day 84) to Day 119] | Pain severity will be evaluated by rating pain on a scale from 0 (no pain) to 10 (pain as bad as you can imagine) for the 'worst', 'least', and 'average' pain experienced in the past 24 hours, as well as, the pain experienced 'now'. In addition, a calculated mean pain severity score will be based on the sum of all 4 of the pain scores divided by 4. If any of the 4 questions are missing, then the calculated mean pain severity score will be considered missing. High values indicate worse outcome. |
| Brief Pain Inventory: Interference With Function Summary Measure | 5 Weeks [Baseline (Day 84) to Day 119] | Pain interference with daily functioning will be evaluated by rating interference on a scale from 0 (does not interfere) to 10 (completely interferes) for 'general activity', 'mood', 'walking ability', 'normal work', 'relation with other people', 'sleep', and 'enjoyment of life'. A calculated mean pain interference will be based on the sum of non-missing interference questions answered divided by the number of questions answered. The mean should be set to missing if fewer than 4 pain interference questions are answered. A high score is worse. |
| Short-Form McGill Pain Questionnaire (SF-MPQ): Summary Score | 5 Weeks [Baseline (Day 84) to Day 119] | The SF-MPQ consists of a 15 item pain rating index. The severity of each item will be scored as None (0), Mild (1), Moderate (2), or Severe (3). The total SF-MPQ score is the sum of the severity scores for each item. The total score can range from 0 to 45; high score is worse. |
| Brief Pain Inventory (BPI): Pain Severity, Worst | 5 Weeks [Baseline (Day 84) to Day 119 Visit] | 'Worst' pain experienced in the past 24 hours. Brief Pain Inventory (BPI): Scale: 0 = No Pain, 10 = Pain as bad as you can imagine; a high score indicates a worse outcome. |
| Patient Global Impression of Change (PGIC) | 5 Weeks [Baseline (Day 84) to Day 119 / Treatment Failure] | The PGIC rating represents observed changes (if any) from the subject's Baseline Visit in activity limitations, symptoms, emotions, and overall quality of life, related to the subject's painful condition. Change is rated on a 7-point Likert-type scale from 1 (no change) through 7 (a great deal better). High score is better outcome. |
| Oral Opioid Supplement Consumption | 5 Weeks [Baseline (Day 84) to Day 119] | Total consumption (mg) = The total number of milligrams consumed of any oral opioid product from Day 84 (Baseline) through the end of study will be calculated for each subject. |
| Time to Rescue - Rescue Medication Given | 5 Weeks [Baseline (Day 84) to Day 119] | Number of subjects with rescue medication given |
| Time to Rescue Medication After Randomization (Days) | 5 Weeks [Baseline (Day 84) to Day 119] | The number of days to rescue will be calculated by calculating the number of hours between the time of randomization and the time of rescue. The number of hours will then be divided by 24 to obtain the number of days. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Hydromorphone Hydrochloride (Randomized/Double-Blind) Subjects stay on their current dose of Hydromorphone Hydrochloride administered via intrathecal (IT) pump; depending on the subject's starting dose on hydromorphone hydrochloride, either a 2 mg/mL or 10 mg/mL formulation may be used.
Programmable Implantable pump: Programmable Implantable pump delivering intrathecal hydromorphone | 41 |
| Hydromorphone Titrated Downward/Control (Randomized/Double-Blind) Subjects have their current dose of Hydromorphone Hydrochloride dose titrated downward; administered via Intrathecal pump | 40 |
| Not Randomized (Open Label Only) Enrolled but Not Randomized, dropped out during Open Label phase. Open Label treatment only of their current dose of Hydromorphone Hydrochloride administered via intrathecal (IT) pump; depending on the subject's starting dose on hydromorphone hydrochloride, either a 2 mg/mL or 10 mg/mL formulation may be used.
Hydromorphone Hydrochloride: Opioid for chronic pain
Device: Programmable Implantable pump delivering intrathecal hydromorphone hydrochloride | 72 |
| Total | 153 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Open Label Phase | Adverse Event | 0 | 0 | 8 |
| Open Label Phase | Changes In The Subject's Condition Render The Subject Unacceptable For Further Treatment | 0 | 0 | 1 |
| Open Label Phase | Inadequate Pain Control | 0 | 0 | 37 |
| Open Label Phase | Investigator Decision | 0 | 0 | 1 |
| Open Label Phase | Non-compliance With Study Drug | 0 | 0 | 3 |
| Open Label Phase | Other, Specify in text field in database | 0 | 0 | 14 |
| Open Label Phase | Protocol Violation | 0 | 0 | 1 |
| Open Label Phase | Sponsor Decision | 0 | 0 | 2 |
| Open Label Phase | Withdrawal by Subject | 0 | 0 | 5 |
| Randomized Phase | Adverse Event | 0 | 1 | 0 |
| Randomized Phase | Inadequate Pain Control | 1 | 2 | 0 |
| Randomized Phase | Lost to Follow-up | 1 | 0 | 0 |
| Randomized Phase | Other, Specify text field in database | 1 | 3 | 0 |
Baseline characteristics
| Characteristic | Hydromorphone Hydrochloride (Randomized/Double-Blind) | Total | Not Randomized (Open Label Only) | Hydromorphone Titrated Downward/Control (Randomized/Double-Blind) |
|---|---|---|---|---|
| Age, Continuous | 53.6 years STANDARD_DEVIATION 11.5 | 55.6 years STANDARD_DEVIATION 10 | 57.1 years STANDARD_DEVIATION 9.7 | 54.8 years STANDARD_DEVIATION 8.3 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 6 Participants | 3 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 40 Participants | 147 Participants | 69 Participants | 38 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 8 Participants | 2 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 38 Participants | 144 Participants | 70 Participants | 36 Participants |
| Region of Enrollment United States | 41 participants | 153 participants | 72 participants | 40 participants |
| Sex: Female, Male Female | 27 Participants | 92 Participants | 40 Participants | 25 Participants |
| Sex: Female, Male Male | 14 Participants | 61 Participants | 32 Participants | 15 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 41 | 0 / 40 | 0 / 72 | 0 / 153 |
| other Total, other adverse events | 35 / 41 | 36 / 40 | 56 / 72 | 127 / 153 |
| serious Total, serious adverse events | 2 / 41 | 6 / 40 | 9 / 72 | 17 / 153 |
Outcome results
Primary
Proportion of Subjects Who Are Treatment Failures During the Double-blind Randomized Withdrawal Period
Treatment failure during the Randomized Phase is defined as at least one of the following: a) increase of \>= 20mm VASPI vs. baseline over 5 days; b) intolerable pain that in investigator's opinion requires intervention; or c) pain-related interventions that violate protocol from Day 84 to Day 119. Note: Baseline pain for the randomized phase is defined as the average of the last 5 days with daily pain measurements while on an optimal intrathecal dose of Hydromorphone, between Days 77 and 83 of the open label dosing period. Note: A subject who does not have sufficient data for evaluation, drops out for any other reasons that are not listed above or who experiences withdrawal syndrome as identified by COWS \> 12 during the randomized phase will not be classified as a treatment failure. Note: Analysis period is from beginning of randomization phase (Day 84) to end of study.
Time frame: 5 weeks [Baseline (Day 84) to Day 119 Visit]
Population: Intent-to-Treat - Randomized Subjects. Subjects in the Open Label Phase of the study who discontinued the study prior to the Randomization Phase and/or did not meet the criteria for randomization are not included in this analysis as they were not randomized to a treatment group.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Hydromorphone Hydrochloride (Randomized/Double-Blind) | Proportion of Subjects Who Are Treatment Failures During the Double-blind Randomized Withdrawal Period | 18 Participants |
| Hydromorphone Hydrochloride Titrated Downward/Control (Randomized/Double-Blind) | Proportion of Subjects Who Are Treatment Failures During the Double-blind Randomized Withdrawal Period | 24 Participants |
Comparison: Superiority of intrathecal hydromorphone hydrochloride as compared to a control arm.p-value: 0.147Chi-squared
Secondary
Brief Pain Inventory (BPI): Pain Severity Average
'Average' pain experienced in the past 24 hours. The Brief Pain Inventory (BPI): Scale: 0 = No Pain, 10 = Pain as bad as you can imagine; a high score indicates a worse outcome.
Time frame: 5 Weeks [Baseline (Day 84) to Day 119]
Population: Intent-to-Treat - Randomized. Subjects in the Open Label Phase of the study who discontinued the study prior to the Randomization Phase and/or did not meet the criteria for randomization are not included in this analysis as they were not randomized to a treatment group.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Hydromorphone Hydrochloride (Randomized/Double-Blind) | Brief Pain Inventory (BPI): Pain Severity Average | 4.09 score on a scale | Standard Error 0.34 |
| Hydromorphone Hydrochloride Titrated Downward/Control (Randomized/Double-Blind) | Brief Pain Inventory (BPI): Pain Severity Average | 4.78 score on a scale | Standard Error 0.35 |
Comparison: P-value by ANCOVA, with randomization group as the factor and initial parameter value as covariate.~Note: For subjects with missing endpoint on Day 119, value is imputed using the Last Observation Carried Forward (LOCF).~Note: Baseline for this analysis is the Day 84 visit.p-value: 0.1642ANCOVA
Secondary
Brief Pain Inventory (BPI): Pain Severity Summary Measure
Pain severity will be evaluated by rating pain on a scale from 0 (no pain) to 10 (pain as bad as you can imagine) for the 'worst', 'least', and 'average' pain experienced in the past 24 hours, as well as, the pain experienced 'now'. In addition, a calculated mean pain severity score will be based on the sum of all 4 of the pain scores divided by 4. If any of the 4 questions are missing, then the calculated mean pain severity score will be considered missing. High values indicate worse outcome.
Time frame: 5 Weeks [Baseline (Day 84) to Day 119]
Population: Intent-to-Treat - Randomized. Subjects in the Open Label Phase of the study who discontinued the study prior to the Randomization Phase and/or did not meet the criteria for randomization are not included in this analysis as they were not randomized to a treatment group.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Hydromorphone Hydrochloride (Randomized/Double-Blind) | Brief Pain Inventory (BPI): Pain Severity Summary Measure | 4.19 score on scale | Standard Error 0.35 |
| Hydromorphone Hydrochloride Titrated Downward/Control (Randomized/Double-Blind) | Brief Pain Inventory (BPI): Pain Severity Summary Measure | 5.24 score on scale | Standard Error 0.36 |
Comparison: P-value by ANCOVA, with randomization group as the factor and initial parameter value as covariate.~Note: For subjects with missing endpoint on Day 119, value is imputed using the Last Observation Carried Forward (LOCF).~Note: Baseline for this analysis is the Day 84 visit.p-value: 0.016ANCOVA
Secondary
Brief Pain Inventory (BPI): Pain Severity, Worst
'Worst' pain experienced in the past 24 hours. Brief Pain Inventory (BPI): Scale: 0 = No Pain, 10 = Pain as bad as you can imagine; a high score indicates a worse outcome.
Time frame: 5 Weeks [Baseline (Day 84) to Day 119 Visit]
Population: Intent-to-Treat - Randomized. Subjects in the Open Label Phase of the study who discontinued the study prior to the Randomization Phase and/or did not meet the criteria for randomization are not included in this analysis as they were not randomized to a treatment group.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Hydromorphone Hydrochloride (Randomized/Double-Blind) | Brief Pain Inventory (BPI): Pain Severity, Worst | 5.62 score on a scale | Standard Error 0.42 |
| Hydromorphone Hydrochloride Titrated Downward/Control (Randomized/Double-Blind) | Brief Pain Inventory (BPI): Pain Severity, Worst | 6.62 score on a scale | Standard Error 0.43 |
Comparison: P-value by ANCOVA, with randomization group as the factor and initial parameter value as covariate.~Note: For subjects with missing endpoint on Day 119, value is imputed using the Last Observation Carried Forward (LOCF).~Note: Baseline for this analysis is the Day 84 visit.p-value: 0.0342ANCOVA
Secondary
Brief Pain Inventory: Interference With Function Summary Measure
Pain interference with daily functioning will be evaluated by rating interference on a scale from 0 (does not interfere) to 10 (completely interferes) for 'general activity', 'mood', 'walking ability', 'normal work', 'relation with other people', 'sleep', and 'enjoyment of life'. A calculated mean pain interference will be based on the sum of non-missing interference questions answered divided by the number of questions answered. The mean should be set to missing if fewer than 4 pain interference questions are answered. A high score is worse.
Time frame: 5 Weeks [Baseline (Day 84) to Day 119]
Population: Intent-to-Treat - Randomized. Subjects in the Open Label Phase of the study who discontinued the study prior to the Randomization Phase and/or did not meet the criteria for randomization are not included in this analysis as they were not randomized to a treatment group.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Hydromorphone Hydrochloride (Randomized/Double-Blind) | Brief Pain Inventory: Interference With Function Summary Measure | 3.76 score on scale | Standard Error 0.44 |
| Hydromorphone Hydrochloride Titrated Downward/Control (Randomized/Double-Blind) | Brief Pain Inventory: Interference With Function Summary Measure | 5.54 score on scale | Standard Error 0.45 |
Comparison: P-value by ANCOVA, with randomization group as the factor and initial parameter value as covariate.~Note: For subjects with missing endpoint on Day 119, value is imputed using the Last Observation Carried Forward (LOCF).~Note: Baseline for this analysis is the Day 84 visit.p-value: 0.0007ANCOVA
Secondary
Oral Opioid Supplement Consumption
Total consumption (mg) = The total number of milligrams consumed of any oral opioid product from Day 84 (Baseline) through the end of study will be calculated for each subject.
Time frame: 5 Weeks [Baseline (Day 84) to Day 119]
Population: Intent-to-Treat - Randomized. Subjects in the Open Label Phase of the study who discontinued the study prior to the Randomization Phase and/or did not meet the criteria for randomization are not included in this analysis as they were not randomized to a treatment group.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Hydromorphone Hydrochloride (Randomized/Double-Blind) | Oral Opioid Supplement Consumption | 6916.88 milligrams (mg) | Standard Deviation 14102.91 |
| Hydromorphone Hydrochloride Titrated Downward/Control (Randomized/Double-Blind) | Oral Opioid Supplement Consumption | 1732.84 milligrams (mg) | Standard Deviation 5984.53 |
Secondary
Patient Global Impression of Change (PGIC)
The PGIC rating represents observed changes (if any) from the subject's Baseline Visit in activity limitations, symptoms, emotions, and overall quality of life, related to the subject's painful condition. Change is rated on a 7-point Likert-type scale from 1 (no change) through 7 (a great deal better). High score is better outcome.
Time frame: 5 Weeks [Baseline (Day 84) to Day 119 / Treatment Failure]
Population: Intent-to-Treat - Randomized. Subjects in the Open Label Phase of the study who discontinued the study prior to the Randomization Phase and/or did not meet the criteria for randomization are not included in this analysis as they were not randomized to a treatment group.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Hydromorphone Hydrochloride (Randomized/Double-Blind) | Patient Global Impression of Change (PGIC) | 4.95 score on a scale | Standard Deviation 1.7 |
| Hydromorphone Hydrochloride Titrated Downward/Control (Randomized/Double-Blind) | Patient Global Impression of Change (PGIC) | 3.73 score on a scale | Standard Deviation 2.04 |
Comparison: P-value by the Cochran-Mantel-Haenszel mean score test (using equally spaced scores).p-value: 0.0335Cochran-Mantel-Haenszel
Secondary
Short-Form McGill Pain Questionnaire (SF-MPQ): Summary Score
The SF-MPQ consists of a 15 item pain rating index. The severity of each item will be scored as None (0), Mild (1), Moderate (2), or Severe (3). The total SF-MPQ score is the sum of the severity scores for each item. The total score can range from 0 to 45; high score is worse.
Time frame: 5 Weeks [Baseline (Day 84) to Day 119]
Population: Intent-to-Treat - Randomized. Subjects in the Open Label Phase of the study who discontinued the study prior to the Randomization Phase and/or did not meet the criteria for randomization are not included in this analysis as they were not randomized to a treatment group.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Hydromorphone Hydrochloride (Randomized/Double-Blind) | Short-Form McGill Pain Questionnaire (SF-MPQ): Summary Score | 11.05 score on a scale, summed across 15 quest | Standard Error 1.53 |
| Hydromorphone Hydrochloride Titrated Downward/Control (Randomized/Double-Blind) | Short-Form McGill Pain Questionnaire (SF-MPQ): Summary Score | 16.95 score on a scale, summed across 15 quest | Standard Error 1.55 |
Comparison: P-value by ANCOVA, with randomization group as the factor and initial parameter value as covariate.~Note: For subjects with missing endpoint on Day 119, value is imputed using the Last Observation Carried Forward (LOCF).~Note: Baseline for this analysis is the Day 84 visit.p-value: 0.0088ANCOVA
Secondary
Time to Rescue Medication After Randomization (Days)
The number of days to rescue will be calculated by calculating the number of hours between the time of randomization and the time of rescue. The number of hours will then be divided by 24 to obtain the number of days.
Time frame: 5 Weeks [Baseline (Day 84) to Day 119]
Population: Intent-to-Treat - Randomized. Subjects in the Open Label Phase of the study who discontinued the study prior to the Randomization Phase and/or did not meet the criteria for randomization are not included in this analysis as they were not randomized to a treatment group.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Hydromorphone Hydrochloride (Randomized/Double-Blind) | Time to Rescue Medication After Randomization (Days) | 28.85 days | Standard Deviation 6.32 |
| Hydromorphone Hydrochloride Titrated Downward/Control (Randomized/Double-Blind) | Time to Rescue Medication After Randomization (Days) | 24.35 days | Standard Deviation 9.67 |
p-value: 0.011Log Rank
Secondary
Time to Rescue - Rescue Medication Given
Number of subjects with rescue medication given
Time frame: 5 Weeks [Baseline (Day 84) to Day 119]
Population: Intent-to-Treat - Randomized. Subjects in the Open Label Phase of the study who discontinued the study prior to the Randomization Phase and/or did not meet the criteria for randomization are not included in this analysis as they were not randomized to a treatment group.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Hydromorphone Hydrochloride (Randomized/Double-Blind) | Time to Rescue - Rescue Medication Given | 16 Participants |
| Hydromorphone Hydrochloride Titrated Downward/Control (Randomized/Double-Blind) | Time to Rescue - Rescue Medication Given | 27 Participants |
p-value: 0.01Chi-squared