Pain
Conditions
Keywords
Pain, Hydromorphone hydrochloride, Oxycodone hydrochloride
Brief summary
The purpose of this study is to compare the safety and efficacy of Oral Osmotic Therapeutic System (OROS) hydromorphone hydrochloride (HCl) with controlled-release oxycodone HCl in participants with cancer-related pain.
Detailed description
This is a double-blind (a medical research study in which neither the researchers nor the participants know what treatment the participants is receiving), randomized (study drug is assigned by chance), multi-center (when more than one hospital or medical school team work on a medical research study), comparative, parallel-group (a clinical trial comparing the response in two or more groups of participants receiving different treatments) study of OROS hydromorphone HCl compared with oxycodone HCl controlled-release in participants with moderate to severe cancer (abnormal tissue that grows and spreads in the body until it kills) pain. The study will consist of 3 phases: a screening period (up to 14 days before randomization), a dose titration phase (up to 8 days), and a dose maintenance phase (28 days). The study visits will be scheduled at weekly intervals. Eligible participants will be randomly assigned to receive either hydromorphone HCl once daily or oxycodone HCl twice daily (placebo will be administered when necessary for blinding). During titration phase, dosage of hydromorphone HCl or oxycodone HCl will be adjusted upward or downward to achieve stable pain control. It can be from 2 days to 8 days. Participants who complete dose titration will enter into the dose maintenance phase and will receive study treatment for 28 consecutive days. Morphine hydrochloride will be given as rescue analgesic (drug used to control pain) medication for breakthrough pain during the study. Primarily efficacy will be evaluated by measuring change in the score of Brief Pain Inventory (BPI) questionnaire item 'worst pain' at end of maintenance period. Participants' safety will be monitored throughout the study.
Interventions
DRUGHydromorphone HCl
Hydromorphone HCl will be administered in dose of 8, 16, 24, and 32 milligram (mg), once daily for 2 to 8 days of Titration phase and 28 days of Maintenance phase. Starting dose will be based on participant's previous daily opioid dose.
DRUGOxycodone HCl CR
Oxycodone HCl will be administered in dose of 10, 20, 30 and 40 mg, twice daily for 2 to 8 days of titration phase and 28 days of maintenance phase. Starting dose will be based on participant's previous daily opioids dose.
DRUGPlacebo
Placebo will be administered to the participants receiving hydromorphone HCl or oxycodone HCl CR along with the study treatment to maintain necessary blinding.
Sponsors
Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Participants receiving strong oral or transdermal (through the skin) opioid analgesics with inadequate control of moderate to severe (very serious, life threatening) cancer pain or who presented with cancer pain and will be eligible to move to Step 3 of the WHO analgesic ladder when receiving weak opioids * Participants who require or are expected to require between 40 mg and 184 mg of oral morphine or morphine equivalents every 24 hours for the chronic management of cancer pain * Participants who are reasonably expected to achieve a stable dose of opioid study medication during the study * Participants who are not expected to start a course of chemotherapy, radiotherapy, targeted cancer therapy, hormone therapy or diphosphates therapy after enrolment into the study. If participants are receiving long-term treatment including hormone therapy, target cancer therapy and diphosphate, the treatment should be kept stable as much as possible from 2 weeks before randomization and up to the completion of the study, encompassing the titration and maintenance phases * Female participants who are premenarchal, postmenopausal, or surgically sterile, abstinent or if sexually active, they must use a medically acceptable method of contraception and must be willing to continue to use the same method of contraception throughout the study
Exclusion criteria
* Participants with neuropathic pain or pain of unknown origin, or acute pain - Participants having pain only on movements * Participants requiring other opioid analgesics (apart from morphine hydrochloride (HCl), in immediate release formulation, allowed as rescue medication for breakthrough pain) * Participants with a recent history (within the previous 6 months) or current history of drug abuse or alcohol abuse * Women of childbearing potential who were pregnant or lactating, seeking pregnancy or failing to use an adequate contraceptive method
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Worst Pain in the Past 24 Hours Assessed by Brief Pain Inventory (BPI) Short Form Questionnaire Score at Day 29 | Baseline and Day 29 | The BPI is questionnaire for evaluating the degree of pain severity and the impact of pain in performing daily routines. Change in worst pain in the past 24 hours in BPI score was reported. The total score ranges from 0 to 10, wherein 0 indicates no pain and 10 indicates pain as bad as participants could imagine. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Pain at Its Least, in the Past 24 Hours Assessed by BPI Short Form Questionnaire Score at Day 29 | Baseline and Day 29 | The BPI is questionnaire for evaluating the degree of pain severity and the impact of pain in performing daily routines. Change in pain at its least, in the past 24 hours in BPI score was reported. The total score ranges from 0 to 10, wherein 0 indicates no pain and 10 indicates pain as bad as participants could imagine. |
| Change From Baseline in Average Pain, in the Past 24 Hours Assessed by BPI Short Form Questionnaire Score at Day 29 | Baseline and Day 29 | The BPI is questionnaire for evaluating the degree of pain severity and the impact of pain in performing daily routines. Change in average pain in the past 24 hours, in BPI score was reported. The score ranges from 0 to 10 wherein, 0 indicates no pain and 10 indicates pain as bad as participants could imagine. |
| Change From Baseline in Pain Right Now Assessed by BPI Short Form Questionnaire Score at Day 29 | Baseline and Day 29 | The BPI is questionnaire for evaluating the degree of pain severity and the impact of pain in performing daily routines. Change in Pain Right now in BPI was reported. The score ranges from 0=no pain to 10=pain as bad as participants could imagine. |
| Change From Baseline in Pain Relief, in the Past 24 Hour Recorded Assessed by BPI Short Form Questionnaire at Day 29 | Baseline and Day 29 | The BPI is questionnaire for evaluating the degree of pain severity and the impact of pain in performing daily routines. BPI comprises of total 9 items in total, and the 8th item consisting of 7 sub-items is a question asking the degree of disturbance due to pain. The score ranges from 0% to 100%, wherein 0% indicates no relief and 100% indicates complete relief. |
| Breakthrough Pain Medication (Rescue Medication) Doses Taken | Baseline up to Day 29 | Any breakthrough pain medication taken during the overall study was reported. Morphine hydrochloride was used as a rescue medication in case of breakthrough pain. |
Countries
China
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Hydromorphone Hydrochloride (HCl) Osmotic Release Oral System (OROS) hydromorphone HCl was administered in dose of 8, 16, 24, and 32 milligram (mg), once daily for 2 to 8 days of titration phase and 28 days of maintenance phase. Starting dose was based on participant's previous daily opioid dose. | 125 |
| Oxycodone HCl Controlled Release (CR) Oxycodone HCl was administered in dose of 10, 20, 30, and 40 mg, twice daily for 2 to 8 days of titration phase and 28 days of maintenance phase. Starting dose was based on participant's previous daily opioid dose. | 123 |
| Total | 248 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Between Titration & Maintenance Phase | Other | 0 | 4 |
| Maintenance Phase | Adverse Event | 3 | 7 |
| Maintenance Phase | Death | 4 | 4 |
| Maintenance Phase | Lost to Follow-up | 5 | 5 |
| Maintenance Phase | More than the maximum dosage required | 5 | 5 |
| Maintenance Phase | Other | 11 | 8 |
| Maintenance Phase | Prohibited drugs used | 1 | 0 |
| Maintenance Phase | Withdrawal by Subject | 8 | 11 |
| Titration Phase | Adverse Event | 5 | 3 |
| Titration Phase | Lost to Follow-up | 2 | 2 |
| Titration Phase | More than maximum dosage required | 2 | 3 |
| Titration Phase | No stable titration dose | 1 | 0 |
| Titration Phase | Other | 8 | 6 |
| Titration Phase | Withdrawal by Subject | 5 | 5 |
Baseline characteristics
| Characteristic | Hydromorphone Hydrochloride (HCl) | Oxycodone HCl Controlled Release (CR) | Total |
|---|---|---|---|
| Age, Continuous | 53.5 Years STANDARD_DEVIATION 10.86 | 52.7 Years STANDARD_DEVIATION 10.75 | 53.1 Years STANDARD_DEVIATION 10.79 |
| Sex: Female, Male Female | 43 Participants | 43 Participants | 86 Participants |
| Sex: Female, Male Male | 82 Participants | 80 Participants | 162 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 102 / 128 | 107 / 126 |
| serious Total, serious adverse events | 11 / 128 | 18 / 126 |
Outcome results
Primary
Change From Baseline in Worst Pain in the Past 24 Hours Assessed by Brief Pain Inventory (BPI) Short Form Questionnaire Score at Day 29
The BPI is questionnaire for evaluating the degree of pain severity and the impact of pain in performing daily routines. Change in worst pain in the past 24 hours in BPI score was reported. The total score ranges from 0 to 10, wherein 0 indicates no pain and 10 indicates pain as bad as participants could imagine.
Time frame: Baseline and Day 29
Population: Per protocol set (PPS) included all randomly assigned participants who had completed all efficacy evaluations, and participants who prematurely discontinued the study due to lack of efficacy were also included. Redefined last observation carried forward (LOCF) was applied. Redefined LOCF is LOCF prior to over dose rescue medication.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Hydromorphone Hydrochloride (HCl) | Change From Baseline in Worst Pain in the Past 24 Hours Assessed by Brief Pain Inventory (BPI) Short Form Questionnaire Score at Day 29 | Baseline | 6.7 Units on a scale | Standard Deviation 1.8 |
| Hydromorphone Hydrochloride (HCl) | Change From Baseline in Worst Pain in the Past 24 Hours Assessed by Brief Pain Inventory (BPI) Short Form Questionnaire Score at Day 29 | Change at Day 29 | -1.8 Units on a scale | Standard Deviation 2.79 |
| Oxycodone HCl Controlled Release (CR) | Change From Baseline in Worst Pain in the Past 24 Hours Assessed by Brief Pain Inventory (BPI) Short Form Questionnaire Score at Day 29 | Baseline | 6.9 Units on a scale | Standard Deviation 1.65 |
| Oxycodone HCl Controlled Release (CR) | Change From Baseline in Worst Pain in the Past 24 Hours Assessed by Brief Pain Inventory (BPI) Short Form Questionnaire Score at Day 29 | Change at Day 29 | -1.8 Units on a scale | Standard Deviation 2.95 |
p-value: 0.85595% CI: [-1.3, 1.1]ANCOVA
Secondary
Breakthrough Pain Medication (Rescue Medication) Doses Taken
Any breakthrough pain medication taken during the overall study was reported. Morphine hydrochloride was used as a rescue medication in case of breakthrough pain.
Time frame: Baseline up to Day 29
Population: The PPS included all randomly assigned participants who had completed all efficacy evaluations, have good compliance to the protocol without major protocol violations specified and who prematurely discontinued the study due to lack of efficacy. Redefined LOCF was applied. Here 'N' =number of participants who were evaluated for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Hydromorphone Hydrochloride (HCl) | Breakthrough Pain Medication (Rescue Medication) Doses Taken | 24.2 Doses | Standard Deviation 24.41 |
| Oxycodone HCl Controlled Release (CR) | Breakthrough Pain Medication (Rescue Medication) Doses Taken | 29.3 Doses | Standard Deviation 24.33 |
p-value: 0.276rank sum test, 2 sided
Secondary
Change From Baseline in Average Pain, in the Past 24 Hours Assessed by BPI Short Form Questionnaire Score at Day 29
The BPI is questionnaire for evaluating the degree of pain severity and the impact of pain in performing daily routines. Change in average pain in the past 24 hours, in BPI score was reported. The score ranges from 0 to 10 wherein, 0 indicates no pain and 10 indicates pain as bad as participants could imagine.
Time frame: Baseline and Day 29
Population: The PPS included all randomly assigned participants who had completed all efficacy evaluations, have good compliance to the protocol without major protocol violations specified and who prematurely discontinued the study due to lack of efficacy were also included. Redefined LOCF was applied.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Hydromorphone Hydrochloride (HCl) | Change From Baseline in Average Pain, in the Past 24 Hours Assessed by BPI Short Form Questionnaire Score at Day 29 | Baseline | 4.7 Units on a scale | Standard Deviation 1.35 |
| Hydromorphone Hydrochloride (HCl) | Change From Baseline in Average Pain, in the Past 24 Hours Assessed by BPI Short Form Questionnaire Score at Day 29 | Change at Day 29 | -1.8 Units on a scale | Standard Deviation 1.98 |
| Oxycodone HCl Controlled Release (CR) | Change From Baseline in Average Pain, in the Past 24 Hours Assessed by BPI Short Form Questionnaire Score at Day 29 | Baseline | 4.7 Units on a scale | Standard Deviation 1.46 |
| Oxycodone HCl Controlled Release (CR) | Change From Baseline in Average Pain, in the Past 24 Hours Assessed by BPI Short Form Questionnaire Score at Day 29 | Change at Day 29 | -1.4 Units on a scale | Standard Deviation 2.53 |
p-value: 0.62195% CI: [-1.1, 0.7]ANCOVA
Secondary
Change From Baseline in Pain at Its Least, in the Past 24 Hours Assessed by BPI Short Form Questionnaire Score at Day 29
The BPI is questionnaire for evaluating the degree of pain severity and the impact of pain in performing daily routines. Change in pain at its least, in the past 24 hours in BPI score was reported. The total score ranges from 0 to 10, wherein 0 indicates no pain and 10 indicates pain as bad as participants could imagine.
Time frame: Baseline and Day 29
Population: The PPS included all randomly assigned participants who had completed all efficacy evaluations, have good compliance to the protocol without major protocol violations specified and who prematurely discontinued the study due to lack of efficacy were also included. Redefined LOCF was applied.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Hydromorphone Hydrochloride (HCl) | Change From Baseline in Pain at Its Least, in the Past 24 Hours Assessed by BPI Short Form Questionnaire Score at Day 29 | Baseline | 2.4 Units on a scale | Standard Deviation 1.63 |
| Hydromorphone Hydrochloride (HCl) | Change From Baseline in Pain at Its Least, in the Past 24 Hours Assessed by BPI Short Form Questionnaire Score at Day 29 | Change at Day 29 | -0.8 Units on a scale | Standard Deviation 1.59 |
| Oxycodone HCl Controlled Release (CR) | Change From Baseline in Pain at Its Least, in the Past 24 Hours Assessed by BPI Short Form Questionnaire Score at Day 29 | Baseline | 2.3 Units on a scale | Standard Deviation 1.37 |
| Oxycodone HCl Controlled Release (CR) | Change From Baseline in Pain at Its Least, in the Past 24 Hours Assessed by BPI Short Form Questionnaire Score at Day 29 | Change at Day 29 | -0.5 Units on a scale | Standard Deviation 2.2 |
p-value: 0.61595% CI: [-1, 0.6]ANCOVA
Secondary
Change From Baseline in Pain Relief, in the Past 24 Hour Recorded Assessed by BPI Short Form Questionnaire at Day 29
The BPI is questionnaire for evaluating the degree of pain severity and the impact of pain in performing daily routines. BPI comprises of total 9 items in total, and the 8th item consisting of 7 sub-items is a question asking the degree of disturbance due to pain. The score ranges from 0% to 100%, wherein 0% indicates no relief and 100% indicates complete relief.
Time frame: Baseline and Day 29
Population: The PPS included all randomly assigned participants who had completed all efficacy evaluations, have good compliance to the protocol without major protocol violations specified and who prematurely discontinued the study due to lack of efficacy were also included. Redefined LOCF was applied.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Hydromorphone Hydrochloride (HCl) | Change From Baseline in Pain Relief, in the Past 24 Hour Recorded Assessed by BPI Short Form Questionnaire at Day 29 | Baseline | 48.8 Units on a scale | Standard Deviation 25.54 |
| Hydromorphone Hydrochloride (HCl) | Change From Baseline in Pain Relief, in the Past 24 Hour Recorded Assessed by BPI Short Form Questionnaire at Day 29 | Change at Day 29 | 15.8 Units on a scale | Standard Deviation 31.29 |
| Oxycodone HCl Controlled Release (CR) | Change From Baseline in Pain Relief, in the Past 24 Hour Recorded Assessed by BPI Short Form Questionnaire at Day 29 | Baseline | 48.0 Units on a scale | Standard Deviation 23.05 |
| Oxycodone HCl Controlled Release (CR) | Change From Baseline in Pain Relief, in the Past 24 Hour Recorded Assessed by BPI Short Form Questionnaire at Day 29 | Change at Day 29 | 14.1 Units on a scale | Standard Deviation 32.01 |
p-value: 0.304ANCOVA
Secondary
Change From Baseline in Pain Right Now Assessed by BPI Short Form Questionnaire Score at Day 29
The BPI is questionnaire for evaluating the degree of pain severity and the impact of pain in performing daily routines. Change in Pain Right now in BPI was reported. The score ranges from 0=no pain to 10=pain as bad as participants could imagine.
Time frame: Baseline and Day 29
Population: The PPS included all randomly assigned participants who had completed all efficacy evaluations, have good compliance to the protocol without major protocol violations specified and who prematurely discontinued the study due to lack of efficacy were also included. Redefined LOCF was applied.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Hydromorphone Hydrochloride (HCl) | Change From Baseline in Pain Right Now Assessed by BPI Short Form Questionnaire Score at Day 29 | Baseline | 4.1 Units on a scale | Standard Deviation 2.09 |
| Hydromorphone Hydrochloride (HCl) | Change From Baseline in Pain Right Now Assessed by BPI Short Form Questionnaire Score at Day 29 | Change at Day 29 | -1.4 Units on a scale | Standard Deviation 2.6 |
| Oxycodone HCl Controlled Release (CR) | Change From Baseline in Pain Right Now Assessed by BPI Short Form Questionnaire Score at Day 29 | Baseline | 4.1 Units on a scale | Standard Deviation 2.19 |
| Oxycodone HCl Controlled Release (CR) | Change From Baseline in Pain Right Now Assessed by BPI Short Form Questionnaire Score at Day 29 | Change at Day 29 | -1.4 Units on a scale | Standard Deviation 3 |
p-value: 0.832ANCOVA