Postoperative Pain
Conditions
Brief summary
The efficacy and safety of oxycodone capsules compared with morphine tablets in hospitalized patients with moderate to severe pain following surgery.
Detailed description
To evaluate the efficacy and safety of oxycodone immediate-release capsules compared with morphine immediate-release tablets in hospitalized patients with moderate to severe pain following surgery.
Interventions
DRUGOxyNorm Capsules
dosage:5mg,l0mg and 20mg dosage form:capsule frequency:every 6h, duration:24 hours
OTHERMorphine tablet
dosage: 10mg and 20mg; dosage form: tablet; frequency: every 6h; duration: 24 hours.
Sponsors
Mundipharma (China) Pharmaceutical Co. Ltd
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
1. Patients of either sex aged 18 to 80 years inclusive. 2. Patients who have given written informed consent to participate in the study. 3. Able and willing to communicate with the investigator and his/her staff. 4. Free of anesthesia as assessed through question and answer interaction with nurse at which time oral medication is indicated. 5. Reporting moderate or severe pain (VAS ≥ 4) related to surgery and requesting analgesics for pain relief.
Exclusion criteria
1. Patients have developed tolerance to or dependence on narcotic analgesics and/or alcohol. 2. Patients with ASA ≥ 3 . 3. Have any concomitant medical condition that would be adversely affected by analgesics or confound the quantification of analgesia, or could affect the absorption, metabolism or excretion of the study drugs in any clinically significant fashion. 4. Have known hypersensitivity to any of the study medications or related agents. 5. Have taken analgesic medications within three hours (wash-out) prior to dosing. 6. Have developed complications from the surgical procedure that would confound the study. 7. Have a history of severe iatrogenic adverse experiences. 8. Mothers nursing their infant during the 24 hours following study drug administration, or pregnant women. 9. Patient with Nothing Per Os (NPO) as stated in patient's chart or physician's order. 10. Surgery in patients with epidural anesthesia 11. Patients with Severe impairment of liver at preoperative stage (ALT, AST ≥ 1.5 times upper limit) and abnormal renal function. 12. Patients with medical history of recovering from abnormal surgery anesthesia. 13. Patients with medical history of hypertension (Systolic blood pressure ≥ 180Hg, Diastolic blood pressure 110Hg). 14. Patients with shock. 15. Patients with COPD. 16. According to investigator to determine, patients are in addition the inclusion criteria and
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Visual Analogue Scale (VAS) in Resting Stage at 6hour (6hour±20 Minutes After Administration of First Dose) | Baseline and 6h (±20min) | To measure resting VAS at 6h(±20min) after administration of first dose, assessing the intensity of pain, and to conduct inter-group comparison Visual Analogue Scale 0 10 20 30 40 50 60 70 80 90 100 0 means no pain; 100 means pain as bad as you can image at resting stage |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The Use of Rescue Analgesics During the 24-hour Observation Period | 24 hours after the first dose. | To calculate the subject who used rescue analgesics during the 4 dose interval within the 24-hour observation period and to conduct inter-group comparison |
| VAS in Coughing Stage at 6h (6h±20min After Administration of First Dose) | Baseline and 6h (±20min) | To measure coughing VAS at 6h (±20min) after administration of first dose, assessing the intensity of pain, and to conduct inter-group comparison Visual Analogue Scale 0 10 20 30 40 50 60 70 80 90 100 0 means no pain; 100 means pain as bed as you can image applicable for both resting and coughing stage |
| VAS in Both Resting and Coughing Stage at 0.5h, 2h and 24h After Administration of First Dose | Baseline,0.5h (±5min), 2h (±10min) and 24h (±20min) | To measure the resting and coughing VAS as 0.5h (±5min), 2h (±10min) and 24h (±20min) after administration of first dose, assessing the intensity of pain and to conduct inter-group comparison |
| Satisfaction With Pain Control | 24 hours after administration of first dose | To assess the Satisfaction with pain control during 24 hours after administration of first dose and to conduct inter-group comparison 1. Very Satisfied 2. Satisfied 3. Fair 4. Not Satisfied 5. Not Satisfied at all |
| Comparison of the Total Amount of Study Drugs Used During the 24 Hours | 24 hours after administration of first dose | To calculate the total amount of study drugs used during the 24 hours and to conduct inter-group comparison The study drug administration is average 6 hours,so the maximal is use 4 times in 24 hours. The investigate to evaluate if the subject need to take the 2nd, 3rd and 4th dose after the mandatory the 1st dose. |
| Sleeping Quality Assessment | 24 hours after administration of first dose | To assess Sleeping quality assessment during 24 hours after administration of first dose and to conduct inter-group comparison Sleeping quality scale 1. Very Good 2. Good 3. Fair 4. Bad 5. Very Bad |
Participant flow
Recruitment details
This study is a randomized, double blind, double dummy, multicenter, parallel group, comparative study to compare the efficacy and safety of oxycodone capsule versus morphine tablet. The subject recruited from hospitalized patients poor with moderate to severe pain following surgery. The duration of the study from 2011 Jul to 2011 Dec.
Pre-assignment details
There is no run-in or wash out period involved in this study. On the protocol 240 subjects was planned to be enrolled, but actually 234 subjects was screened and all randomized. Zero screen failure is reasonable for the indication with this study design.
Participants by arm
| Arm | Count |
|---|---|
| OxyNorm Capsules To determine the efficacy and safety of OxyNorm Capsules.
OxyNorm Capsules: dosage:5mg,l0mg and 20mg dosage form:capsule frequency:every 6h, duration:24 hours | 117 |
| Morphine Tablet To determine the efficacy and safety of Morphine tablet.
Morphine tablet: dosage: 10mg and 20mg; dosage form: tablet; frequency: every 6h; duration: 24 hours. | 117 |
| Total | 234 |
Baseline characteristics
| Characteristic | OxyNorm Capsules | Total | Morphine Tablet |
|---|---|---|---|
| Age, Continuous | 43.44 years STANDARD_DEVIATION 11.06 | 43.37 years STANDARD_DEVIATION 10.77 | 43.29 years STANDARD_DEVIATION 10.53 |
| America Society of Anesthesiologist classification P1(Class I) | 61 Participants | 118 Participants | 57 Participants |
| America Society of Anesthesiologist classification P2(Class II) | 56 Participants | 116 Participants | 60 Participants |
| Electrocardiogram test abnormal,clinical significant | 0 Participants | 5 Participants | 5 Participants |
| Electrocardiogram test abnormal, not clinical significant | 29 Participants | 63 Participants | 34 Participants |
| Electrocardiogram test normal | 88 Participants | 164 Participants | 76 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 116 Participants | 233 Participants | 117 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment China | 117 Participants | 234 Participants | 117 Participants |
| Sex: Female, Male Female | 101 Participants | 194 Participants | 93 Participants |
| Sex: Female, Male Male | 16 Participants | 40 Participants | 24 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 117 | 0 / 117 |
| other Total, other adverse events | 35 / 117 | 35 / 117 |
| serious Total, serious adverse events | 0 / 117 | 0 / 117 |
Outcome results
Primary
Visual Analogue Scale (VAS) in Resting Stage at 6hour (6hour±20 Minutes After Administration of First Dose)
To measure resting VAS at 6h(±20min) after administration of first dose, assessing the intensity of pain, and to conduct inter-group comparison Visual Analogue Scale 0 10 20 30 40 50 60 70 80 90 100 0 means no pain; 100 means pain as bad as you can image at resting stage
Time frame: Baseline and 6h (±20min)
Population: 234 subjects in Full Analysis Set (FAS) in which 4 subjects from each group was excluded for Per Protocol(PP) population, so 113 subjects in PP population in each group for the primary endpoint analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| OxyNorm Capsules | Visual Analogue Scale (VAS) in Resting Stage at 6hour (6hour±20 Minutes After Administration of First Dose) | 6th hours Visual Analogue Scale | 20.21 units on a scale | Standard Deviation 15.66 |
| OxyNorm Capsules | Visual Analogue Scale (VAS) in Resting Stage at 6hour (6hour±20 Minutes After Administration of First Dose) | baseline of Visual Analogue Scale | 46.21 units on a scale | Standard Deviation 9.53 |
| Morphine Tablet | Visual Analogue Scale (VAS) in Resting Stage at 6hour (6hour±20 Minutes After Administration of First Dose) | 6th hours Visual Analogue Scale | 19.94 units on a scale | Standard Deviation 15.68 |
| Morphine Tablet | Visual Analogue Scale (VAS) in Resting Stage at 6hour (6hour±20 Minutes After Administration of First Dose) | baseline of Visual Analogue Scale | 45.48 units on a scale | Standard Deviation 7.94 |
Secondary
Comparison of the Total Amount of Study Drugs Used During the 24 Hours
To calculate the total amount of study drugs used during the 24 hours and to conduct inter-group comparison The study drug administration is average 6 hours,so the maximal is use 4 times in 24 hours. The investigate to evaluate if the subject need to take the 2nd, 3rd and 4th dose after the mandatory the 1st dose.
Time frame: 24 hours after administration of first dose
Population: 234 subjects in Full Analysis Set (FAS) in which 4 subjects from each group was excluded for Per Protocol(PP) population, so 113 subjects in PP population in each group for the primary endpoint analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| OxyNorm Capsules | Comparison of the Total Amount of Study Drugs Used During the 24 Hours | 18.50 mg | Standard Deviation 10.37 |
| Morphine Tablet | Comparison of the Total Amount of Study Drugs Used During the 24 Hours | 39.82 mg | Standard Deviation 21.79 |
Secondary
Satisfaction With Pain Control
To assess the Satisfaction with pain control during 24 hours after administration of first dose and to conduct inter-group comparison 1. Very Satisfied 2. Satisfied 3. Fair 4. Not Satisfied 5. Not Satisfied at all
Time frame: 24 hours after administration of first dose
Population: 234 subjects in Full Analysis Set (FAS) in which 4 subjects from each group was excluded for Per Protocol(PP) population, so 113 subjects in PP population in each group for the primary endpoint analysis.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| OxyNorm Capsules | Satisfaction With Pain Control | Very Satisfied | 38 Participants |
| OxyNorm Capsules | Satisfaction With Pain Control | Not Satisfied | 2 Participants |
| OxyNorm Capsules | Satisfaction With Pain Control | Satisfied | 54 Participants |
| OxyNorm Capsules | Satisfaction With Pain Control | Not Satisfied at all | 0 Participants |
| OxyNorm Capsules | Satisfaction With Pain Control | Fair | 19 Participants |
| Morphine Tablet | Satisfaction With Pain Control | Not Satisfied at all | 0 Participants |
| Morphine Tablet | Satisfaction With Pain Control | Very Satisfied | 43 Participants |
| Morphine Tablet | Satisfaction With Pain Control | Fair | 12 Participants |
| Morphine Tablet | Satisfaction With Pain Control | Not Satisfied | 0 Participants |
| Morphine Tablet | Satisfaction With Pain Control | Satisfied | 58 Participants |
Secondary
Sleeping Quality Assessment
To assess Sleeping quality assessment during 24 hours after administration of first dose and to conduct inter-group comparison Sleeping quality scale 1. Very Good 2. Good 3. Fair 4. Bad 5. Very Bad
Time frame: 24 hours after administration of first dose
Population: 234 subjects in Full Analysis Set (FAS) in which 4 subjects from each group was excluded for Per Protocol(PP) population, so 113 subjects in PP population in each group for the primary endpoint analysis.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| OxyNorm Capsules | Sleeping Quality Assessment | Good | 38 Participants |
| OxyNorm Capsules | Sleeping Quality Assessment | Bad | 5 Participants |
| OxyNorm Capsules | Sleeping Quality Assessment | Fair | 38 Participants |
| OxyNorm Capsules | Sleeping Quality Assessment | Very Bad | 1 Participants |
| OxyNorm Capsules | Sleeping Quality Assessment | Very Good | 31 Participants |
| Morphine Tablet | Sleeping Quality Assessment | Very Bad | 1 Participants |
| Morphine Tablet | Sleeping Quality Assessment | Very Good | 36 Participants |
| Morphine Tablet | Sleeping Quality Assessment | Good | 48 Participants |
| Morphine Tablet | Sleeping Quality Assessment | Fair | 26 Participants |
| Morphine Tablet | Sleeping Quality Assessment | Bad | 2 Participants |
Secondary
The Use of Rescue Analgesics During the 24-hour Observation Period
To calculate the subject who used rescue analgesics during the 4 dose interval within the 24-hour observation period and to conduct inter-group comparison
Time frame: 24 hours after the first dose.
Population: in FAS population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| OxyNorm Capsules | The Use of Rescue Analgesics During the 24-hour Observation Period | First dose interval(0-6h) | 7 Participants |
| OxyNorm Capsules | The Use of Rescue Analgesics During the 24-hour Observation Period | Second dose interval(7-12h) | 8 Participants |
| OxyNorm Capsules | The Use of Rescue Analgesics During the 24-hour Observation Period | Third dose interval(13-18) | 1 Participants |
| OxyNorm Capsules | The Use of Rescue Analgesics During the 24-hour Observation Period | Fourth dose interval(19-24h) | 3 Participants |
| Morphine Tablet | The Use of Rescue Analgesics During the 24-hour Observation Period | Fourth dose interval(19-24h) | 2 Participants |
| Morphine Tablet | The Use of Rescue Analgesics During the 24-hour Observation Period | First dose interval(0-6h) | 5 Participants |
| Morphine Tablet | The Use of Rescue Analgesics During the 24-hour Observation Period | Third dose interval(13-18) | 0 Participants |
| Morphine Tablet | The Use of Rescue Analgesics During the 24-hour Observation Period | Second dose interval(7-12h) | 2 Participants |
Secondary
VAS in Both Resting and Coughing Stage at 0.5h, 2h and 24h After Administration of First Dose
To measure the resting and coughing VAS as 0.5h (±5min), 2h (±10min) and 24h (±20min) after administration of first dose, assessing the intensity of pain and to conduct inter-group comparison
Time frame: Baseline,0.5h (±5min), 2h (±10min) and 24h (±20min)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| OxyNorm Capsules | VAS in Both Resting and Coughing Stage at 0.5h, 2h and 24h After Administration of First Dose | Resting baseline of Visual Analogue Scale | 46.21 units on a scale | Standard Deviation 9.53 |
| OxyNorm Capsules | VAS in Both Resting and Coughing Stage at 0.5h, 2h and 24h After Administration of First Dose | Resting VAS 24 hours after first dose | 9.73 units on a scale | Standard Deviation 12.52 |
| OxyNorm Capsules | VAS in Both Resting and Coughing Stage at 0.5h, 2h and 24h After Administration of First Dose | Coughing VAS 24hours after first dose | 17.11 units on a scale | Standard Deviation 13.51 |
| OxyNorm Capsules | VAS in Both Resting and Coughing Stage at 0.5h, 2h and 24h After Administration of First Dose | Coughing baseline of Visual Analogue Scale | 55.16 units on a scale | Standard Deviation 12.15 |
| OxyNorm Capsules | VAS in Both Resting and Coughing Stage at 0.5h, 2h and 24h After Administration of First Dose | Resting visual analogue scale before first dose | 46.21 units on a scale | Standard Deviation 9.53 |
| OxyNorm Capsules | VAS in Both Resting and Coughing Stage at 0.5h, 2h and 24h After Administration of First Dose | Coughing visual analogue scale before first dose | 55.20 units on a scale | Standard Deviation 12.12 |
| OxyNorm Capsules | VAS in Both Resting and Coughing Stage at 0.5h, 2h and 24h After Administration of First Dose | Resting VAS 0.5 hour after first dose | 29.87 units on a scale | Standard Deviation 13.59 |
| OxyNorm Capsules | VAS in Both Resting and Coughing Stage at 0.5h, 2h and 24h After Administration of First Dose | Coughing VAS 0.5 hour after first dose | 39.21 units on a scale | Standard Deviation 16.56 |
| OxyNorm Capsules | VAS in Both Resting and Coughing Stage at 0.5h, 2h and 24h After Administration of First Dose | Resting VAS 2 hours after first dose | 20.58 units on a scale | Standard Deviation 14.4 |
| OxyNorm Capsules | VAS in Both Resting and Coughing Stage at 0.5h, 2h and 24h After Administration of First Dose | Coughing VAS 2hours after first dose | 29.68 units on a scale | Standard Deviation 17.91 |
| Morphine Tablet | VAS in Both Resting and Coughing Stage at 0.5h, 2h and 24h After Administration of First Dose | Resting VAS 2 hours after first dose | 20.89 units on a scale | Standard Deviation 12.7 |
| Morphine Tablet | VAS in Both Resting and Coughing Stage at 0.5h, 2h and 24h After Administration of First Dose | Coughing VAS 2hours after first dose | 29.30 units on a scale | Standard Deviation 13.76 |
| Morphine Tablet | VAS in Both Resting and Coughing Stage at 0.5h, 2h and 24h After Administration of First Dose | Coughing VAS 24hours after first dose | 16.27 units on a scale | Standard Deviation 12.58 |
| Morphine Tablet | VAS in Both Resting and Coughing Stage at 0.5h, 2h and 24h After Administration of First Dose | Resting baseline of Visual Analogue Scale | 45.48 units on a scale | Standard Deviation 7.96 |
| Morphine Tablet | VAS in Both Resting and Coughing Stage at 0.5h, 2h and 24h After Administration of First Dose | Resting VAS 0.5 hour after first dose | 29.80 units on a scale | Standard Deviation 12.39 |
| Morphine Tablet | VAS in Both Resting and Coughing Stage at 0.5h, 2h and 24h After Administration of First Dose | Resting visual analogue scale before first dose | 45.48 units on a scale | Standard Deviation 7.96 |
| Morphine Tablet | VAS in Both Resting and Coughing Stage at 0.5h, 2h and 24h After Administration of First Dose | Resting VAS 24 hours after first dose | 9.75 units on a scale | Standard Deviation 11.19 |
| Morphine Tablet | VAS in Both Resting and Coughing Stage at 0.5h, 2h and 24h After Administration of First Dose | Coughing baseline of Visual Analogue Scale | 53.91 units on a scale | Standard Deviation 10.39 |
| Morphine Tablet | VAS in Both Resting and Coughing Stage at 0.5h, 2h and 24h After Administration of First Dose | Coughing visual analogue scale before first dose | 53.91 units on a scale | Standard Deviation 10.39 |
| Morphine Tablet | VAS in Both Resting and Coughing Stage at 0.5h, 2h and 24h After Administration of First Dose | Coughing VAS 0.5 hour after first dose | 37.96 units on a scale | Standard Deviation 13.61 |
Secondary
VAS in Coughing Stage at 6h (6h±20min After Administration of First Dose)
To measure coughing VAS at 6h (±20min) after administration of first dose, assessing the intensity of pain, and to conduct inter-group comparison Visual Analogue Scale 0 10 20 30 40 50 60 70 80 90 100 0 means no pain; 100 means pain as bed as you can image applicable for both resting and coughing stage
Time frame: Baseline and 6h (±20min)
Population: 234 subjects in Full Analysis Set (FAS) in which 4 subjects from each group was excluded for Per Protocol(PP) population, so 113 subjects in PP population in each group for the primary endpoint analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| OxyNorm Capsules | VAS in Coughing Stage at 6h (6h±20min After Administration of First Dose) | Visual Analogue Scale of baseline coughing | 55.16 units on a scale | Standard Deviation 12.15 |
| OxyNorm Capsules | VAS in Coughing Stage at 6h (6h±20min After Administration of First Dose) | Visual Analogue Scale after 6hours coughing | 28.81 units on a scale | Standard Deviation 17.58 |
| Morphine Tablet | VAS in Coughing Stage at 6h (6h±20min After Administration of First Dose) | Visual Analogue Scale of baseline coughing | 53.91 units on a scale | Standard Deviation 10.39 |
| Morphine Tablet | VAS in Coughing Stage at 6h (6h±20min After Administration of First Dose) | Visual Analogue Scale after 6hours coughing | 28.15 units on a scale | Standard Deviation 16.79 |