Chronic Noncancer Pain
Conditions
Keywords
Chronic noncancer pain, oxycodone, naltrexone
Brief summary
The study will provide information to assess the benefits versus risks of extended exposure to oxycodone HCl and naltrexone HCl extended-release capsules in a chronic noncancer pain population.
Interventions
DRUGoxycodone HCl and naltrexone HCl extended-release capsules
Daily dose range of 20 mg to 160 mg of the oxycodone component in a 24 hour time interval, administered twice daily approximately 12 hours apart (At the discretion of the Investigator, oxycodone HCl and naltrexone HCl extended-release capsules may be administered once daily, at 24 hour intervals.)
Sponsors
Pfizer
Study design
Primary purpose
SUPPORTIVE_CARE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Subject has moderate to severe chronic noncancer pain (duration of at least 3 months) requiring a continuous around-the-clock opioid analgesic for an extended period of time. Conditions may include, but are not limited to, osteoarthritis, chronic low back pain, or other opioid -responsive pain conditions. * Subject agrees to refrain from taking opioid medications other than study drug during the study. (The exception is during the Pre-Treatment Period when the subject may continue current opioid therapy to guide first 4 weeks of the Treatment Period when the subject may administer immediate-release oxycodone to support conversion to study drug.)
Exclusion criteria
* Subject has moderate or severe chronic pain due to cancer, migraine, recent trauma, infection, or other pain expected to be short-term (duration less than 3 months). * Subject has a documented history of alcohol or drug abuse within 1 year prior to study entry that in the Investigator's judgment would impact subject participation. * Subject has ongoing or active alcohol or drug abuse that in the Investigator's judgment would impact subject participation. * Subject has a positive urine drug test for illicit drug use or medications at screening without legitimate medical explanation. * Subject has a clinically significant medical condition (e.g., cardiovascular, neurological, renal, hepatic, pulmonary, gastrointestinal, endocrine, hematological, immunological, rheumatological, metabolic, or psychiatric) or physical examination, vital signs (VS), 12-lead electrocardiogram (ECG), clinical laboratory abnormalities that in the opinion of the Investigator would impact the safety of the subject during study participation. * If female, the subject is pregnant or breast-feeding. * Subject has a known history or known hypersensitivity to oxycodone, oxycodone salts, naltrexone or acetaminophen,or pharmacological similar compounds. * Subject is historically non-responsive to oxycodone treatment or requires greater than 160 mg oxycodone in a 24-hour time interval.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment-Emergent Adverse Events (AEs) and Adverse Reactions | Baseline up to end of study (2 weeks post-end of month 12) | An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An AE that was attributed to study drug in a participant who received study drug was defined as an adverse reaction. Treatment-emergent are events between first dose of study drug and up to end of study (2 weeks post-end of month 12) that were absent before treatment or that worsened relative to pretreatment state. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment Emergent (TE) Adverse Events (AEs) Based on Intensity | Baseline up to end of study (2 weeks post-end of month 12) | An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Intensity of adverse event was defined on the basis of severity of an event and was classified as; mild (does not interfere with participant's usual function), moderate (interferes to some extent with participant's usual function) and severe (interferes significantly with participant's usual function). Treatment-emergent are events between first dose of study drug and up to end of study (2 weeks post-end of month 12) that were absent before treatment or that worsened relative to pretreatment state. |
| Percentage of Participants With Clinical Opiate Withdrawal Scale (COWS) Score | Baseline up to Month 12 | The presence and level of clinical opiate withdrawal signs or symptoms was determined by clinician-administered, clinical opiate withdrawal scale (COWS). It contains 11 common opiate withdrawal signs or symptoms rated by clinician (resting pulse rate, gastrointestinal upset, sweating, tremor, restlessness, yawning, pupil size, anxiety or irritability, bone or joint aches, gooseflesh skin, runny nose or tearing), rated on either 3-point, 4-point or 5-point scale, higher score indicated more symptoms of withdrawal. The total score is the sum of all items, ranging from 0 to 48, higher score indicated severe withdrawal. Participants were categorized as less than mild (score 0-4) mild (score 5-12), moderate (score 13-24), moderately severe (score 25-36) or severe (score greater than 36). Percentage of participants with mild (score 5-12), moderate (score 13-24), moderately severe (score 25-36) or severe (score greater than 36) were reported. |
| Subjective Opiate Withdrawal Scale (SOWS) Score | Baseline, Week 1, 4, Month 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 | The presence and level of clinical opiate withdrawal signs or symptoms was determined by participant-reported instrument, subjective opiate withdrawal scale (SOWS). It contains 16 symptoms of opiate withdrawal rated by the participant (anxiety, yawning, sweating, tearing, running nose, goose bumps, shaking, hot flashes, cold flashes, bone or muscle aches, restlessness, nauseous, vomiting, muscle twitch, stomach cramps and feel like using now). Each item is rated on a 5-point scale (0= not at all, 1= a little, 2= moderate, 3= quite a bit, 4= extreme). The total score is the sum of all items, ranging from 0 to 64, higher score indicated severe withdrawal. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Time to Stabilization of Study Medication | Baseline up to Month 12 | Stabilization was considered to have occurred when: total daily dose of oxycodone and naltrexone remained unchanged for greater than or equal to (\>=) 3 consecutive days, daily acetaminophen used remained at 1 gram or less and immediate-release oxycodone was not being used as a rescue medication. Days to stabilization = date of stabilization - date of first dose + 1. |
| Duration of Exposure to Study Medication | Baseline up to 2 weeks after last dose | Duration of exposure to study medication during the course of the study was assessed. |
| Mean Daily Dose of Study Medication (Oxycodone Component) | Baseline- less than (<) Week 1, Week 1-<4, Week 4-<Month 2, Month 2-<3, Month 3-<4, Month 4-< 5, Month 5-<6, Month 6-<7, Month 7-<8, Month8-<9, Month 9-<10, Month 10-<11, Month 11-<12, Month 12-<End of study (2 weeks post end of Month 12) | — |
| Number of Participants With Rescue Medication (Acetaminophen Tablets) | Baseline- less than (<) Week 1, Week 1-<4, Week 4-<Month 2, Month 2-<3, Month 3-<4, Month 4-< 5, Month 5-<6, Month 6-<7, Month 7-<8, Month8-<9, Month 9-<10, Month 10-<11, Month 11-<12, Month 12-<End of study (2 weeks post end of Month 12) | Participants had acetaminophen up to 2 grams per day during the treatment period of the study as rescue medication. |
| Percentage of Participants With Response to Urine Drug Test | Screening, Week 4, Month 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 or early termination | Participants with a positive urine drug test for illicit drug substances (marijuana, cocaine, amphetamines, methamphetamines, phencyclidine, and ecstasy), or unexpected drug substances (those other than reported by the participant as therapeutic concomitant medications such as opiates and methadone), or a negative urine test for the expected opioid (oxycodone) was assessed. |
| Observed Steady-state Plasma Concentrations (Cobs) of 6-Beta-naltrexol | Week 1, 4, Month 2, 3, 6, 9, 12 or early termination | 6-Beta-naltrexol was a metabolite of naltrexone. |
| Mean Daily Dose of Immediate-release Oxycodone as Rescue Medication | Up to Week 4 | Immediate-release oxycodone as a single ingredient product was used as a rescue medication only during the first 4 weeks of the treatment period to support the initiation of oxycodone HCl and naltrexone HCl treatment. |
| Participants Global Assessment of Treatment Satisfaction | Week 1, 4, Month 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, end of treatment | Participant global assessment of treatment satisfaction was scored on a 5-point categorical scale based on response to the question Please rate your overall satisfaction with the study drug you received? where 1 = very dissatisfied, 2 = dissatisfied, 3 = neither satisfied nor dissatisfied, 4 = satisfied, 5 = very satisfied. |
| Mean Change From Baseline in Pain Right Now Score at Weeks 1, 4, Months 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 12 or Early Termination | Baseline, Week 1, 4, Months 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 12 or Early Termination (ET) | The pain intensity scale consisted of 4 questions (pain at its worst in the last 24 hours, pain at its least in the last 24 hours, pain on the average in the last 24 hours and pain right now) each scored on an 11-point numerical rating scale, where 0 = no pain and 10 = pain as bad as you can imagine. Pain right now was reported. |
| Mean Change From Baseline in Average Pain Score at Weeks 1, 4, Months 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 12 or Early Termination | Baseline, Week 1, 4, Months 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 12 or Early Termination | The pain intensity scale consisted of 4 questions (pain at its worst in the last 24 hours, pain at its least in the last 24 hours, pain on the average in the last 24 hours and pain right now) each scored on an 11-point numerical rating scale, where 0 = no pain and 10 = pain as bad as you can imagine. Pain on average in the last 24 hours was reported. |
| Mean Change From Baseline in Worst Pain Score at Weeks 1, 4, Months 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 12 or Early Termination | Baseline, Week 1, 4, Months 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 12 or Early Termination | The pain intensity scale consisted of 4 questions (pain at its worst in the last 24 hours, pain at its least in the last 24 hours, pain on the average in the last 24 hours and pain right now) each scored on an 11-point numerical rating scale, where 0 = no pain and 10 = pain as bad as you can imagine. Pain at its worst in the last 24 hours was reported. |
| Percentage of Participants With Current Opioid Misuse Measure (COMM) Score of 9 or Above | Baseline, Week 4, Month 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 or early termination | The COMM is a 17-item self-report questionnaire to monitor for aberrant medication-related behaviors among chronic pain participants. Participants are asked to indicate the frequency of individual behaviors on a scale from 0 to 4 (0 = never, 1 = seldom, 2 = sometimes, 3 = often, 4= very often). The total COMM score is the sum of the 17 item scores with a range from 0 to 68. Higher score indicated a higher risk for aberrant medication- related behavior. A score of 9 or higher was defined as high risk for aberrant medication- related behavior. |
| Observed Steady-state Plasma Concentrations (Cobs) of Oxycodone | Week 1, 4, Month 2, 3, 6, 9, 12 or early termination | — |
| Observed Steady-state Plasma Concentrations (Cobs) of Noroxycodone | Week 1, 4, Month 2, 3, 6, 9, 12 or early termination | Noroxycodone was a metabolite of Oxycodone. |
| Observed Steady-state Plasma Concentrations (Cobs) of Naltrexone | Week 1, 4, Month 2, 3, 6, 9, 12 or early termination | — |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Oxycodone Hydrochloride (HCl) and Naltrexone HCl Participants received oxycodone HCl and naltrexone HCl extended-release capsules at an allowable total daily dose range of 20 milligram (mg) oxycodone HCl /2.4 mg naltrexone HCl to 160 mg oxycodone HCl /19.2 mg naltrexone HCl, once daily or twice daily, as per investigators' discretion, for 12 months. Following Month 12, dose might be tapered from the current total daily dose of oxycodone HCl and naltrexone HCl extended-release capsules to the Investigator-determined standard of care based on investigator's discretion. | 395 |
| Total | 395 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 75 |
| Overall Study | Confirmed positive urine drug test | 8 |
| Overall Study | Death | 1 |
| Overall Study | Lack of Efficacy | 37 |
| Overall Study | Lost to Follow-up | 17 |
| Overall Study | Non-compliant | 25 |
| Overall Study | Other | 6 |
| Overall Study | Physician Decision | 12 |
| Overall Study | Pregnancy | 1 |
| Overall Study | Protocol Violation | 1 |
| Overall Study | Sponsor's request | 3 |
| Overall Study | Withdrawal by Subject | 51 |
Baseline characteristics
| Characteristic | Oxycodone Hydrochloride (HCl) and Naltrexone HCl |
|---|---|
| Age, Continuous | 53.8 years STANDARD_DEVIATION 12.1 |
| Sex: Female, Male Female | 203 Participants |
| Sex: Female, Male Male | 192 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 272 / 395 |
| serious Total, serious adverse events | 26 / 395 |
Outcome results
Primary
Number of Participants With Treatment-Emergent Adverse Events (AEs) and Adverse Reactions
An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An AE that was attributed to study drug in a participant who received study drug was defined as an adverse reaction. Treatment-emergent are events between first dose of study drug and up to end of study (2 weeks post-end of month 12) that were absent before treatment or that worsened relative to pretreatment state.
Time frame: Baseline up to end of study (2 weeks post-end of month 12)
Population: Safety analysis set included all enrolled participants who had at least 1 dose of oxycodone HCl and naltrexone HCl extended-release capsules.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Oxycodone Hydrochloride (HCl) and Naltrexone HCl | Number of Participants With Treatment-Emergent Adverse Events (AEs) and Adverse Reactions | Adverse event (all causalities) | 343 participants |
| Oxycodone Hydrochloride (HCl) and Naltrexone HCl | Number of Participants With Treatment-Emergent Adverse Events (AEs) and Adverse Reactions | Adverse reaction | 207 participants |
Secondary
Number of Participants With Treatment Emergent (TE) Adverse Events (AEs) Based on Intensity
An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Intensity of adverse event was defined on the basis of severity of an event and was classified as; mild (does not interfere with participant's usual function), moderate (interferes to some extent with participant's usual function) and severe (interferes significantly with participant's usual function). Treatment-emergent are events between first dose of study drug and up to end of study (2 weeks post-end of month 12) that were absent before treatment or that worsened relative to pretreatment state.
Time frame: Baseline up to end of study (2 weeks post-end of month 12)
Population: Safety analysis set included all enrolled participants who had at least 1 dose of oxycodone HCl and naltrexone HCl extended-release capsules.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Oxycodone Hydrochloride (HCl) and Naltrexone HCl | Number of Participants With Treatment Emergent (TE) Adverse Events (AEs) Based on Intensity | Mild | 94 participants |
| Oxycodone Hydrochloride (HCl) and Naltrexone HCl | Number of Participants With Treatment Emergent (TE) Adverse Events (AEs) Based on Intensity | Moderate | 202 participants |
| Oxycodone Hydrochloride (HCl) and Naltrexone HCl | Number of Participants With Treatment Emergent (TE) Adverse Events (AEs) Based on Intensity | Severe | 47 participants |
Secondary
Percentage of Participants With Clinical Opiate Withdrawal Scale (COWS) Score
The presence and level of clinical opiate withdrawal signs or symptoms was determined by clinician-administered, clinical opiate withdrawal scale (COWS). It contains 11 common opiate withdrawal signs or symptoms rated by clinician (resting pulse rate, gastrointestinal upset, sweating, tremor, restlessness, yawning, pupil size, anxiety or irritability, bone or joint aches, gooseflesh skin, runny nose or tearing), rated on either 3-point, 4-point or 5-point scale, higher score indicated more symptoms of withdrawal. The total score is the sum of all items, ranging from 0 to 48, higher score indicated severe withdrawal. Participants were categorized as less than mild (score 0-4) mild (score 5-12), moderate (score 13-24), moderately severe (score 25-36) or severe (score greater than 36). Percentage of participants with mild (score 5-12), moderate (score 13-24), moderately severe (score 25-36) or severe (score greater than 36) were reported.
Time frame: Baseline up to Month 12
Population: Safety analysis set included all enrolled participants who had at least 1 dose of oxycodone HCl and naltrexone HCl extended-release capsules.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Oxycodone Hydrochloride (HCl) and Naltrexone HCl | Percentage of Participants With Clinical Opiate Withdrawal Scale (COWS) Score | Mild (score 5-12) | 13.2 percentage of participants |
| Oxycodone Hydrochloride (HCl) and Naltrexone HCl | Percentage of Participants With Clinical Opiate Withdrawal Scale (COWS) Score | Moderate (score 13-24) | 0.0 percentage of participants |
| Oxycodone Hydrochloride (HCl) and Naltrexone HCl | Percentage of Participants With Clinical Opiate Withdrawal Scale (COWS) Score | Moderately severe (score 25-36) | 0.3 percentage of participants |
| Oxycodone Hydrochloride (HCl) and Naltrexone HCl | Percentage of Participants With Clinical Opiate Withdrawal Scale (COWS) Score | Severe (score greater than 36) | 0.0 percentage of participants |
Secondary
Subjective Opiate Withdrawal Scale (SOWS) Score
The presence and level of clinical opiate withdrawal signs or symptoms was determined by participant-reported instrument, subjective opiate withdrawal scale (SOWS). It contains 16 symptoms of opiate withdrawal rated by the participant (anxiety, yawning, sweating, tearing, running nose, goose bumps, shaking, hot flashes, cold flashes, bone or muscle aches, restlessness, nauseous, vomiting, muscle twitch, stomach cramps and feel like using now). Each item is rated on a 5-point scale (0= not at all, 1= a little, 2= moderate, 3= quite a bit, 4= extreme). The total score is the sum of all items, ranging from 0 to 64, higher score indicated severe withdrawal.
Time frame: Baseline, Week 1, 4, Month 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12
Population: Safety analysis set included all enrolled participants who had at least 1 dose of oxycodone HCl and naltrexone HCl extended-release capsules. Here n signifies those participants who were evaluable at specified time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Oxycodone Hydrochloride (HCl) and Naltrexone HCl | Subjective Opiate Withdrawal Scale (SOWS) Score | Baseline (n= 395) | 5.4 units on a scale | Standard Deviation 5.49 |
| Oxycodone Hydrochloride (HCl) and Naltrexone HCl | Subjective Opiate Withdrawal Scale (SOWS) Score | Week 1 (n= 362) | 4.6 units on a scale | Standard Deviation 6.15 |
| Oxycodone Hydrochloride (HCl) and Naltrexone HCl | Subjective Opiate Withdrawal Scale (SOWS) Score | Week 4 (n= 307) | 3.6 units on a scale | Standard Deviation 4.32 |
| Oxycodone Hydrochloride (HCl) and Naltrexone HCl | Subjective Opiate Withdrawal Scale (SOWS) Score | Month 2 (n= 252) | 3.6 units on a scale | Standard Deviation 4.7 |
| Oxycodone Hydrochloride (HCl) and Naltrexone HCl | Subjective Opiate Withdrawal Scale (SOWS) Score | Month 3 (n= 221) | 3.3 units on a scale | Standard Deviation 4.53 |
| Oxycodone Hydrochloride (HCl) and Naltrexone HCl | Subjective Opiate Withdrawal Scale (SOWS) Score | Month 4 (n= 210) | 2.9 units on a scale | Standard Deviation 4.3 |
| Oxycodone Hydrochloride (HCl) and Naltrexone HCl | Subjective Opiate Withdrawal Scale (SOWS) Score | Month 5 (n= 198) | 3.2 units on a scale | Standard Deviation 4.56 |
| Oxycodone Hydrochloride (HCl) and Naltrexone HCl | Subjective Opiate Withdrawal Scale (SOWS) Score | Month 6 (n= 190) | 2.5 units on a scale | Standard Deviation 3.27 |
| Oxycodone Hydrochloride (HCl) and Naltrexone HCl | Subjective Opiate Withdrawal Scale (SOWS) Score | Month 7 (n= 185) | 2.4 units on a scale | Standard Deviation 4.07 |
| Oxycodone Hydrochloride (HCl) and Naltrexone HCl | Subjective Opiate Withdrawal Scale (SOWS) Score | Month 8 (n= 180) | 2.5 units on a scale | Standard Deviation 3.74 |
| Oxycodone Hydrochloride (HCl) and Naltrexone HCl | Subjective Opiate Withdrawal Scale (SOWS) Score | Month 9 (n= 174) | 2.4 units on a scale | Standard Deviation 4.08 |
| Oxycodone Hydrochloride (HCl) and Naltrexone HCl | Subjective Opiate Withdrawal Scale (SOWS) Score | Month 10 (n= 167) | 2.2 units on a scale | Standard Deviation 3.25 |
| Oxycodone Hydrochloride (HCl) and Naltrexone HCl | Subjective Opiate Withdrawal Scale (SOWS) Score | Month 11 (n= 162) | 2.3 units on a scale | Standard Deviation 3.53 |
| Oxycodone Hydrochloride (HCl) and Naltrexone HCl | Subjective Opiate Withdrawal Scale (SOWS) Score | Month 12 (n= 154) | 2.4 units on a scale | Standard Deviation 4.09 |
Other Pre-specified
Duration of Exposure to Study Medication
Duration of exposure to study medication during the course of the study was assessed.
Time frame: Baseline up to 2 weeks after last dose
Population: Safety analysis set included all enrolled participants who had at least 1 dose of oxycodone HCl and naltrexone HCl extended-release capsules.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Oxycodone Hydrochloride (HCl) and Naltrexone HCl | Duration of Exposure to Study Medication | 171.0 days |
Other Pre-specified
Mean Change From Baseline in Average Pain Score at Weeks 1, 4, Months 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 12 or Early Termination
The pain intensity scale consisted of 4 questions (pain at its worst in the last 24 hours, pain at its least in the last 24 hours, pain on the average in the last 24 hours and pain right now) each scored on an 11-point numerical rating scale, where 0 = no pain and 10 = pain as bad as you can imagine. Pain on average in the last 24 hours was reported.
Time frame: Baseline, Week 1, 4, Months 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 12 or Early Termination
Population: ITT. Here N (number of participants analyzed) signifies those participants who were evaluable for this measure and n signifies those participants who were evaluable at specified time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Oxycodone Hydrochloride (HCl) and Naltrexone HCl | Mean Change From Baseline in Average Pain Score at Weeks 1, 4, Months 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 12 or Early Termination | Baseline (n= 384) | 5.9 unit on a scale | Standard Deviation 1.74 |
| Oxycodone Hydrochloride (HCl) and Naltrexone HCl | Mean Change From Baseline in Average Pain Score at Weeks 1, 4, Months 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 12 or Early Termination | Change at Week 1 (n= 357) | -0.6 unit on a scale | Standard Deviation 1.64 |
| Oxycodone Hydrochloride (HCl) and Naltrexone HCl | Mean Change From Baseline in Average Pain Score at Weeks 1, 4, Months 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 12 or Early Termination | Change at Week 4 (n= 303) | -1.2 unit on a scale | Standard Deviation 1.95 |
| Oxycodone Hydrochloride (HCl) and Naltrexone HCl | Mean Change From Baseline in Average Pain Score at Weeks 1, 4, Months 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 12 or Early Termination | Change at Month 2 (n= 250) | -1.5 unit on a scale | Standard Deviation 2.11 |
| Oxycodone Hydrochloride (HCl) and Naltrexone HCl | Mean Change From Baseline in Average Pain Score at Weeks 1, 4, Months 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 12 or Early Termination | Change at Month 3 (n= 219) | -1.7 unit on a scale | Standard Deviation 2.12 |
| Oxycodone Hydrochloride (HCl) and Naltrexone HCl | Mean Change From Baseline in Average Pain Score at Weeks 1, 4, Months 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 12 or Early Termination | Change at Month 4 (n= 206) | -1.7 unit on a scale | Standard Deviation 2.04 |
| Oxycodone Hydrochloride (HCl) and Naltrexone HCl | Mean Change From Baseline in Average Pain Score at Weeks 1, 4, Months 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 12 or Early Termination | Change at Month 5 (n= 196) | -1.7 unit on a scale | Standard Deviation 2.02 |
| Oxycodone Hydrochloride (HCl) and Naltrexone HCl | Mean Change From Baseline in Average Pain Score at Weeks 1, 4, Months 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 12 or Early Termination | Change at Month 6 (n= 189) | -1.7 unit on a scale | Standard Deviation 2.11 |
| Oxycodone Hydrochloride (HCl) and Naltrexone HCl | Mean Change From Baseline in Average Pain Score at Weeks 1, 4, Months 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 12 or Early Termination | Change at Month 7 (n= 184) | -1.7 unit on a scale | Standard Deviation 2.17 |
| Oxycodone Hydrochloride (HCl) and Naltrexone HCl | Mean Change From Baseline in Average Pain Score at Weeks 1, 4, Months 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 12 or Early Termination | Change at Month 8 (n= 180) | -1.9 unit on a scale | Standard Deviation 2.12 |
| Oxycodone Hydrochloride (HCl) and Naltrexone HCl | Mean Change From Baseline in Average Pain Score at Weeks 1, 4, Months 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 12 or Early Termination | Change at Month 9 (n= 173) | -1.8 unit on a scale | Standard Deviation 2.21 |
| Oxycodone Hydrochloride (HCl) and Naltrexone HCl | Mean Change From Baseline in Average Pain Score at Weeks 1, 4, Months 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 12 or Early Termination | Change at Month 10 (n= 166) | -1.7 unit on a scale | Standard Deviation 2.26 |
| Oxycodone Hydrochloride (HCl) and Naltrexone HCl | Mean Change From Baseline in Average Pain Score at Weeks 1, 4, Months 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 12 or Early Termination | Change at Month 11 (n= 161) | -1.8 unit on a scale | Standard Deviation 2.02 |
| Oxycodone Hydrochloride (HCl) and Naltrexone HCl | Mean Change From Baseline in Average Pain Score at Weeks 1, 4, Months 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 12 or Early Termination | Change at Month 12 (n= 153) | -1.9 unit on a scale | Standard Deviation 2.23 |
| Oxycodone Hydrochloride (HCl) and Naltrexone HCl | Mean Change From Baseline in Average Pain Score at Weeks 1, 4, Months 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 12 or Early Termination | Change at Month 12/ET (n= 372) | -1.3 unit on a scale | Standard Deviation 2.32 |
Other Pre-specified
Mean Change From Baseline in Pain Right Now Score at Weeks 1, 4, Months 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 12 or Early Termination
The pain intensity scale consisted of 4 questions (pain at its worst in the last 24 hours, pain at its least in the last 24 hours, pain on the average in the last 24 hours and pain right now) each scored on an 11-point numerical rating scale, where 0 = no pain and 10 = pain as bad as you can imagine. Pain right now was reported.
Time frame: Baseline, Week 1, 4, Months 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 12 or Early Termination (ET)
Population: ITT. Here N (number of participants analyzed) signifies those participants who were evaluable for this measure and n signifies those participants who were evaluable at specified time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Oxycodone Hydrochloride (HCl) and Naltrexone HCl | Mean Change From Baseline in Pain Right Now Score at Weeks 1, 4, Months 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 12 or Early Termination | Baseline (n= 386) | 5.6 units on a scale | Standard Deviation 2.17 |
| Oxycodone Hydrochloride (HCl) and Naltrexone HCl | Mean Change From Baseline in Pain Right Now Score at Weeks 1, 4, Months 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 12 or Early Termination | Change at Week 1 (n= 360) | -0.6 units on a scale | Standard Deviation 2.16 |
| Oxycodone Hydrochloride (HCl) and Naltrexone HCl | Mean Change From Baseline in Pain Right Now Score at Weeks 1, 4, Months 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 12 or Early Termination | Change at Week 4 (n= 306) | -1.3 units on a scale | Standard Deviation 2.29 |
| Oxycodone Hydrochloride (HCl) and Naltrexone HCl | Mean Change From Baseline in Pain Right Now Score at Weeks 1, 4, Months 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 12 or Early Termination | Change at Month 2 (n= 251) | -1.6 units on a scale | Standard Deviation 2.36 |
| Oxycodone Hydrochloride (HCl) and Naltrexone HCl | Mean Change From Baseline in Pain Right Now Score at Weeks 1, 4, Months 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 12 or Early Termination | Change at Month 3 (n= 218) | -1.7 units on a scale | Standard Deviation 2.34 |
| Oxycodone Hydrochloride (HCl) and Naltrexone HCl | Mean Change From Baseline in Pain Right Now Score at Weeks 1, 4, Months 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 12 or Early Termination | Change at Month 4 (n= 208) | -1.8 units on a scale | Standard Deviation 2.29 |
| Oxycodone Hydrochloride (HCl) and Naltrexone HCl | Mean Change From Baseline in Pain Right Now Score at Weeks 1, 4, Months 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 12 or Early Termination | Change at Month 5 (n= 197) | -1.8 units on a scale | Standard Deviation 2.29 |
| Oxycodone Hydrochloride (HCl) and Naltrexone HCl | Mean Change From Baseline in Pain Right Now Score at Weeks 1, 4, Months 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 12 or Early Termination | Change at Month 6 (n= 189) | -1.8 units on a scale | Standard Deviation 2.38 |
| Oxycodone Hydrochloride (HCl) and Naltrexone HCl | Mean Change From Baseline in Pain Right Now Score at Weeks 1, 4, Months 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 12 or Early Termination | Change at Month 7 (n= 184) | -1.7 units on a scale | Standard Deviation 2.4 |
| Oxycodone Hydrochloride (HCl) and Naltrexone HCl | Mean Change From Baseline in Pain Right Now Score at Weeks 1, 4, Months 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 12 or Early Termination | Change at Month 8 (n= 180) | -1.8 units on a scale | Standard Deviation 2.48 |
| Oxycodone Hydrochloride (HCl) and Naltrexone HCl | Mean Change From Baseline in Pain Right Now Score at Weeks 1, 4, Months 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 12 or Early Termination | Change at Month 9 (n= 172) | -1.8 units on a scale | Standard Deviation 2.39 |
| Oxycodone Hydrochloride (HCl) and Naltrexone HCl | Mean Change From Baseline in Pain Right Now Score at Weeks 1, 4, Months 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 12 or Early Termination | Change at Month 10 (n= 166) | -1.7 units on a scale | Standard Deviation 2.41 |
| Oxycodone Hydrochloride (HCl) and Naltrexone HCl | Mean Change From Baseline in Pain Right Now Score at Weeks 1, 4, Months 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 12 or Early Termination | Change at Month 11 (n= 161) | -1.9 units on a scale | Standard Deviation 2.31 |
| Oxycodone Hydrochloride (HCl) and Naltrexone HCl | Mean Change From Baseline in Pain Right Now Score at Weeks 1, 4, Months 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 12 or Early Termination | Change at Month 12 (n= 153) | -1.9 units on a scale | Standard Deviation 2.44 |
| Oxycodone Hydrochloride (HCl) and Naltrexone HCl | Mean Change From Baseline in Pain Right Now Score at Weeks 1, 4, Months 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 12 or Early Termination | Change at Month 12/ET (n= 373) | -1.4 units on a scale | Standard Deviation 2.58 |
Other Pre-specified
Mean Change From Baseline in Worst Pain Score at Weeks 1, 4, Months 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 12 or Early Termination
The pain intensity scale consisted of 4 questions (pain at its worst in the last 24 hours, pain at its least in the last 24 hours, pain on the average in the last 24 hours and pain right now) each scored on an 11-point numerical rating scale, where 0 = no pain and 10 = pain as bad as you can imagine. Pain at its worst in the last 24 hours was reported.
Time frame: Baseline, Week 1, 4, Months 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 12 or Early Termination
Population: ITT. Here N (number of participants analyzed) signifies those participants who were evaluable for this measure and n signifies those participants who were evaluable at specified time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Oxycodone Hydrochloride (HCl) and Naltrexone HCl | Mean Change From Baseline in Worst Pain Score at Weeks 1, 4, Months 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 12 or Early Termination | Baseline (n= 382) | 7.4 unit on a scale | Standard Deviation 1.63 |
| Oxycodone Hydrochloride (HCl) and Naltrexone HCl | Mean Change From Baseline in Worst Pain Score at Weeks 1, 4, Months 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 12 or Early Termination | Change at Week 1 (n= 354) | -0.7 unit on a scale | Standard Deviation 1.96 |
| Oxycodone Hydrochloride (HCl) and Naltrexone HCl | Mean Change From Baseline in Worst Pain Score at Weeks 1, 4, Months 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 12 or Early Termination | Change at Week 4 (n= 301) | -1.3 unit on a scale | Standard Deviation 2.24 |
| Oxycodone Hydrochloride (HCl) and Naltrexone HCl | Mean Change From Baseline in Worst Pain Score at Weeks 1, 4, Months 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 12 or Early Termination | Change at Month 2 (n= 248) | -1.6 unit on a scale | Standard Deviation 2.39 |
| Oxycodone Hydrochloride (HCl) and Naltrexone HCl | Mean Change From Baseline in Worst Pain Score at Weeks 1, 4, Months 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 12 or Early Termination | Change at Month 3 (n= 219) | -1.8 unit on a scale | Standard Deviation 2.32 |
| Oxycodone Hydrochloride (HCl) and Naltrexone HCl | Mean Change From Baseline in Worst Pain Score at Weeks 1, 4, Months 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 12 or Early Termination | Change at Month 4 (n= 208) | -1.9 unit on a scale | Standard Deviation 2.12 |
| Oxycodone Hydrochloride (HCl) and Naltrexone HCl | Mean Change From Baseline in Worst Pain Score at Weeks 1, 4, Months 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 12 or Early Termination | Change at Month 5 (n= 197) | -1.9 unit on a scale | Standard Deviation 2.41 |
| Oxycodone Hydrochloride (HCl) and Naltrexone HCl | Mean Change From Baseline in Worst Pain Score at Weeks 1, 4, Months 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 12 or Early Termination | Change at Month 6 (n= 189) | -2.0 unit on a scale | Standard Deviation 2.3 |
| Oxycodone Hydrochloride (HCl) and Naltrexone HCl | Mean Change From Baseline in Worst Pain Score at Weeks 1, 4, Months 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 12 or Early Termination | Change at Month 7 (n= 184) | -2.0 unit on a scale | Standard Deviation 2.43 |
| Oxycodone Hydrochloride (HCl) and Naltrexone HCl | Mean Change From Baseline in Worst Pain Score at Weeks 1, 4, Months 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 12 or Early Termination | Change at Month 8 (n= 180) | -2.0 unit on a scale | Standard Deviation 2.31 |
| Oxycodone Hydrochloride (HCl) and Naltrexone HCl | Mean Change From Baseline in Worst Pain Score at Weeks 1, 4, Months 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 12 or Early Termination | Change at Month 9 (n= 173) | -2.2 unit on a scale | Standard Deviation 2.48 |
| Oxycodone Hydrochloride (HCl) and Naltrexone HCl | Mean Change From Baseline in Worst Pain Score at Weeks 1, 4, Months 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 12 or Early Termination | Change at Month 10 (n= 166) | -2.1 unit on a scale | Standard Deviation 2.5 |
| Oxycodone Hydrochloride (HCl) and Naltrexone HCl | Mean Change From Baseline in Worst Pain Score at Weeks 1, 4, Months 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 12 or Early Termination | Change at Month 11 (n= 161) | -2.2 unit on a scale | Standard Deviation 2.41 |
| Oxycodone Hydrochloride (HCl) and Naltrexone HCl | Mean Change From Baseline in Worst Pain Score at Weeks 1, 4, Months 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 12 or Early Termination | Change at Month 12 (n= 153) | -2.2 unit on a scale | Standard Deviation 2.44 |
| Oxycodone Hydrochloride (HCl) and Naltrexone HCl | Mean Change From Baseline in Worst Pain Score at Weeks 1, 4, Months 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 12 or Early Termination | Change at Month 12/ET (n= 368) | -1.6 unit on a scale | Standard Deviation 2.52 |
Other Pre-specified
Mean Daily Dose of Immediate-release Oxycodone as Rescue Medication
Immediate-release oxycodone as a single ingredient product was used as a rescue medication only during the first 4 weeks of the treatment period to support the initiation of oxycodone HCl and naltrexone HCl treatment.
Time frame: Up to Week 4
Population: Data for mean daily dose of immediate-release oxycodone was not reported because as per protocol and analysis plan it was not planned to be summarized.
Other Pre-specified
Mean Daily Dose of Study Medication (Oxycodone Component)
Time frame: Baseline- less than (<) Week 1, Week 1-<4, Week 4-<Month 2, Month 2-<3, Month 3-<4, Month 4-< 5, Month 5-<6, Month 6-<7, Month 7-<8, Month8-<9, Month 9-<10, Month 10-<11, Month 11-<12, Month 12-<End of study (2 weeks post end of Month 12)
Population: Safety analysis set. Here N (number of participants analyzed) signifies those participants who were evaluable for this measure and n signifies those participants who were evaluable at specified time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Oxycodone Hydrochloride (HCl) and Naltrexone HCl | Mean Daily Dose of Study Medication (Oxycodone Component) | Baseline-less than (<) Week 1 (n= 378) | 38.6 milligram/day | Standard Deviation 81.27 |
| Oxycodone Hydrochloride (HCl) and Naltrexone HCl | Mean Daily Dose of Study Medication (Oxycodone Component) | Week 1-<4 (n= 344) | 51.7 milligram/day | Standard Deviation 35.53 |
| Oxycodone Hydrochloride (HCl) and Naltrexone HCl | Mean Daily Dose of Study Medication (Oxycodone Component) | Week 4-<Month 2 (n= 292) | 62.8 milligram/day | Standard Deviation 42.65 |
| Oxycodone Hydrochloride (HCl) and Naltrexone HCl | Mean Daily Dose of Study Medication (Oxycodone Component) | Month 2-< 3 (n= 238) | 66.1 milligram/day | Standard Deviation 40.35 |
| Oxycodone Hydrochloride (HCl) and Naltrexone HCl | Mean Daily Dose of Study Medication (Oxycodone Component) | Month 3-<4 (n= 217) | 68.0 milligram/day | Standard Deviation 40.36 |
| Oxycodone Hydrochloride (HCl) and Naltrexone HCl | Mean Daily Dose of Study Medication (Oxycodone Component) | Month 4-< 5 (n= 205) | 68.6 milligram/day | Standard Deviation 41.49 |
| Oxycodone Hydrochloride (HCl) and Naltrexone HCl | Mean Daily Dose of Study Medication (Oxycodone Component) | Month 5-<6 (n= 193) | 71.5 milligram/day | Standard Deviation 43.58 |
| Oxycodone Hydrochloride (HCl) and Naltrexone HCl | Mean Daily Dose of Study Medication (Oxycodone Component) | Month 6-<7 (n= 183) | 73.1 milligram/day | Standard Deviation 43.22 |
| Oxycodone Hydrochloride (HCl) and Naltrexone HCl | Mean Daily Dose of Study Medication (Oxycodone Component) | Month 7- <8 (n= 183) | 76.7 milligram/day | Standard Deviation 43.76 |
| Oxycodone Hydrochloride (HCl) and Naltrexone HCl | Mean Daily Dose of Study Medication (Oxycodone Component) | Month 8-<9 (n= 177) | 77.7 milligram/day | Standard Deviation 45.67 |
| Oxycodone Hydrochloride (HCl) and Naltrexone HCl | Mean Daily Dose of Study Medication (Oxycodone Component) | Month 9-<10 (n= 169) | 76.5 milligram/day | Standard Deviation 44.58 |
| Oxycodone Hydrochloride (HCl) and Naltrexone HCl | Mean Daily Dose of Study Medication (Oxycodone Component) | Month 10- <11 (n= 163) | 77.9 milligram/day | Standard Deviation 44.45 |
| Oxycodone Hydrochloride (HCl) and Naltrexone HCl | Mean Daily Dose of Study Medication (Oxycodone Component) | Month 11- <12 (n= 160) | 76.2 milligram/day | Standard Deviation 43.14 |
| Oxycodone Hydrochloride (HCl) and Naltrexone HCl | Mean Daily Dose of Study Medication (Oxycodone Component) | Month 12- <End of study (n= 82) | 26.9 milligram/day | Standard Deviation 22.79 |
Other Pre-specified
Number of Participants With Rescue Medication (Acetaminophen Tablets)
Participants had acetaminophen up to 2 grams per day during the treatment period of the study as rescue medication.
Time frame: Baseline- less than (<) Week 1, Week 1-<4, Week 4-<Month 2, Month 2-<3, Month 3-<4, Month 4-< 5, Month 5-<6, Month 6-<7, Month 7-<8, Month8-<9, Month 9-<10, Month 10-<11, Month 11-<12, Month 12-<End of study (2 weeks post end of Month 12)
Population: Intent-to-treat (ITT) included all participants in the safety analysis set who had at least 1 pain intensity score reported during treatment. Here n signifies those participants who were evaluable at specified time point.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Oxycodone Hydrochloride (HCl) and Naltrexone HCl | Number of Participants With Rescue Medication (Acetaminophen Tablets) | Month 10-<11 (n= 167) | 80 participants |
| Oxycodone Hydrochloride (HCl) and Naltrexone HCl | Number of Participants With Rescue Medication (Acetaminophen Tablets) | Month 11-<12 (n= 163) | 85 participants |
| Oxycodone Hydrochloride (HCl) and Naltrexone HCl | Number of Participants With Rescue Medication (Acetaminophen Tablets) | Month 12-<End of study (n= 95) | 30 participants |
| Oxycodone Hydrochloride (HCl) and Naltrexone HCl | Number of Participants With Rescue Medication (Acetaminophen Tablets) | Baseline-<Week 1 (n= 387) | 256 participants |
| Oxycodone Hydrochloride (HCl) and Naltrexone HCl | Number of Participants With Rescue Medication (Acetaminophen Tablets) | Week 1-<4 (n= 361) | 204 participants |
| Oxycodone Hydrochloride (HCl) and Naltrexone HCl | Number of Participants With Rescue Medication (Acetaminophen Tablets) | Week 4-<Month 2 (n= 305) | 167 participants |
| Oxycodone Hydrochloride (HCl) and Naltrexone HCl | Number of Participants With Rescue Medication (Acetaminophen Tablets) | Month 2-<3 (n= 252) | 124 participants |
| Oxycodone Hydrochloride (HCl) and Naltrexone HCl | Number of Participants With Rescue Medication (Acetaminophen Tablets) | Month 3-<4 (n= 222) | 120 participants |
| Oxycodone Hydrochloride (HCl) and Naltrexone HCl | Number of Participants With Rescue Medication (Acetaminophen Tablets) | Month 4-<5 (n= 209) | 112 participants |
| Oxycodone Hydrochloride (HCl) and Naltrexone HCl | Number of Participants With Rescue Medication (Acetaminophen Tablets) | Month 5-<6 (n= 199) | 104 participants |
| Oxycodone Hydrochloride (HCl) and Naltrexone HCl | Number of Participants With Rescue Medication (Acetaminophen Tablets) | Month 6-<7 (n= 191) | 96 participants |
| Oxycodone Hydrochloride (HCl) and Naltrexone HCl | Number of Participants With Rescue Medication (Acetaminophen Tablets) | Month 7-<8 (n= 185) | 96 participants |
| Oxycodone Hydrochloride (HCl) and Naltrexone HCl | Number of Participants With Rescue Medication (Acetaminophen Tablets) | Month8-<9 (n= 179) | 93 participants |
| Oxycodone Hydrochloride (HCl) and Naltrexone HCl | Number of Participants With Rescue Medication (Acetaminophen Tablets) | Month 9-<10 (n= 172) | 79 participants |
Other Pre-specified
Observed Steady-state Plasma Concentrations (Cobs) of 6-Beta-naltrexol
6-Beta-naltrexol was a metabolite of naltrexone.
Time frame: Week 1, 4, Month 2, 3, 6, 9, 12 or early termination
Population: Data was not available to report as PK parameters were plotted by individual participant listings but not summarized for analysis, as per planned analysis.
Other Pre-specified
Observed Steady-state Plasma Concentrations (Cobs) of Naltrexone
Time frame: Week 1, 4, Month 2, 3, 6, 9, 12 or early termination
Population: Data was not available to report as PK parameters were plotted by individual participant listings but not summarized for analysis, as per planned analysis.
Other Pre-specified
Observed Steady-state Plasma Concentrations (Cobs) of Noroxycodone
Noroxycodone was a metabolite of Oxycodone.
Time frame: Week 1, 4, Month 2, 3, 6, 9, 12 or early termination
Population: Data was not available to report as PK parameters were plotted by individual participant listings but not summarized for analysis, as per planned analysis.
Other Pre-specified
Observed Steady-state Plasma Concentrations (Cobs) of Oxycodone
Time frame: Week 1, 4, Month 2, 3, 6, 9, 12 or early termination
Population: Data was not available to report as PK parameters were plotted by individual participant listings but not summarized for analysis, as per planned analysis.
Other Pre-specified
Participants Global Assessment of Treatment Satisfaction
Participant global assessment of treatment satisfaction was scored on a 5-point categorical scale based on response to the question Please rate your overall satisfaction with the study drug you received? where 1 = very dissatisfied, 2 = dissatisfied, 3 = neither satisfied nor dissatisfied, 4 = satisfied, 5 = very satisfied.
Time frame: Week 1, 4, Month 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, end of treatment
Population: ITT. Here N (number of participants analyzed) signifies those participants who were evaluable for this measure and n signifies those participants who were evaluable at specified time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Oxycodone Hydrochloride (HCl) and Naltrexone HCl | Participants Global Assessment of Treatment Satisfaction | Week 1 (n= 361) | 3.3 unit on a scale | Standard Deviation 1.03 |
| Oxycodone Hydrochloride (HCl) and Naltrexone HCl | Participants Global Assessment of Treatment Satisfaction | Week 4 (n= 304) | 3.8 unit on a scale | Standard Deviation 0.99 |
| Oxycodone Hydrochloride (HCl) and Naltrexone HCl | Participants Global Assessment of Treatment Satisfaction | Month 2 (n= 251) | 3.9 unit on a scale | Standard Deviation 0.94 |
| Oxycodone Hydrochloride (HCl) and Naltrexone HCl | Participants Global Assessment of Treatment Satisfaction | Month 3 (n= 220) | 4.1 unit on a scale | Standard Deviation 0.88 |
| Oxycodone Hydrochloride (HCl) and Naltrexone HCl | Participants Global Assessment of Treatment Satisfaction | Month 4 (n= 209) | 4.1 unit on a scale | Standard Deviation 0.93 |
| Oxycodone Hydrochloride (HCl) and Naltrexone HCl | Participants Global Assessment of Treatment Satisfaction | Month 5 (n= 197) | 4.2 unit on a scale | Standard Deviation 0.9 |
| Oxycodone Hydrochloride (HCl) and Naltrexone HCl | Participants Global Assessment of Treatment Satisfaction | Month 6 (n= 190) | 4.2 unit on a scale | Standard Deviation 0.89 |
| Oxycodone Hydrochloride (HCl) and Naltrexone HCl | Participants Global Assessment of Treatment Satisfaction | Month 7 (n= 185) | 4.2 unit on a scale | Standard Deviation 0.81 |
| Oxycodone Hydrochloride (HCl) and Naltrexone HCl | Participants Global Assessment of Treatment Satisfaction | Month 8 (n= 181) | 4.2 unit on a scale | Standard Deviation 0.81 |
| Oxycodone Hydrochloride (HCl) and Naltrexone HCl | Participants Global Assessment of Treatment Satisfaction | Month 9 (n= 174) | 4.2 unit on a scale | Standard Deviation 0.96 |
| Oxycodone Hydrochloride (HCl) and Naltrexone HCl | Participants Global Assessment of Treatment Satisfaction | Month 10 (n= 167) | 4.3 unit on a scale | Standard Deviation 0.73 |
| Oxycodone Hydrochloride (HCl) and Naltrexone HCl | Participants Global Assessment of Treatment Satisfaction | Month 11 (n= 162) | 4.3 unit on a scale | Standard Deviation 0.79 |
| Oxycodone Hydrochloride (HCl) and Naltrexone HCl | Participants Global Assessment of Treatment Satisfaction | Month 12 (n= 154) | 4.2 unit on a scale | Standard Deviation 1.04 |
| Oxycodone Hydrochloride (HCl) and Naltrexone HCl | Participants Global Assessment of Treatment Satisfaction | End of treatment (n= 372) | 3.6 unit on a scale | Standard Deviation 1.27 |
Other Pre-specified
Percentage of Participants With Current Opioid Misuse Measure (COMM) Score of 9 or Above
The COMM is a 17-item self-report questionnaire to monitor for aberrant medication-related behaviors among chronic pain participants. Participants are asked to indicate the frequency of individual behaviors on a scale from 0 to 4 (0 = never, 1 = seldom, 2 = sometimes, 3 = often, 4= very often). The total COMM score is the sum of the 17 item scores with a range from 0 to 68. Higher score indicated a higher risk for aberrant medication- related behavior. A score of 9 or higher was defined as high risk for aberrant medication- related behavior.
Time frame: Baseline, Week 4, Month 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 or early termination
Population: Safety analysis set included all enrolled participants who had at least 1 dose of oxycodone HCl and naltrexone HCl extended-release capsules. Here n signifies those participants who were evaluable at specified time point.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Oxycodone Hydrochloride (HCl) and Naltrexone HCl | Percentage of Participants With Current Opioid Misuse Measure (COMM) Score of 9 or Above | Month 7 (n= 185) | 3.2 percentage of participants |
| Oxycodone Hydrochloride (HCl) and Naltrexone HCl | Percentage of Participants With Current Opioid Misuse Measure (COMM) Score of 9 or Above | Baseline (n= 395) | 21.3 percentage of participants |
| Oxycodone Hydrochloride (HCl) and Naltrexone HCl | Percentage of Participants With Current Opioid Misuse Measure (COMM) Score of 9 or Above | Week 4 (n= 302) | 8.9 percentage of participants |
| Oxycodone Hydrochloride (HCl) and Naltrexone HCl | Percentage of Participants With Current Opioid Misuse Measure (COMM) Score of 9 or Above | Month 2 (n= 250) | 10.0 percentage of participants |
| Oxycodone Hydrochloride (HCl) and Naltrexone HCl | Percentage of Participants With Current Opioid Misuse Measure (COMM) Score of 9 or Above | Month 3 (n= 217) | 8.3 percentage of participants |
| Oxycodone Hydrochloride (HCl) and Naltrexone HCl | Percentage of Participants With Current Opioid Misuse Measure (COMM) Score of 9 or Above | Month 4 (n= 208) | 6.7 percentage of participants |
| Oxycodone Hydrochloride (HCl) and Naltrexone HCl | Percentage of Participants With Current Opioid Misuse Measure (COMM) Score of 9 or Above | Month 5 (n= 197) | 5.1 percentage of participants |
| Oxycodone Hydrochloride (HCl) and Naltrexone HCl | Percentage of Participants With Current Opioid Misuse Measure (COMM) Score of 9 or Above | Month 6 (n= 189) | 2.6 percentage of participants |
| Oxycodone Hydrochloride (HCl) and Naltrexone HCl | Percentage of Participants With Current Opioid Misuse Measure (COMM) Score of 9 or Above | Month 8 (n= 181) | 5.0 percentage of participants |
| Oxycodone Hydrochloride (HCl) and Naltrexone HCl | Percentage of Participants With Current Opioid Misuse Measure (COMM) Score of 9 or Above | Month 9 (n= 174) | 5.7 percentage of participants |
| Oxycodone Hydrochloride (HCl) and Naltrexone HCl | Percentage of Participants With Current Opioid Misuse Measure (COMM) Score of 9 or Above | Month 10 (n= 167) | 4.8 percentage of participants |
| Oxycodone Hydrochloride (HCl) and Naltrexone HCl | Percentage of Participants With Current Opioid Misuse Measure (COMM) Score of 9 or Above | Month 11 (n= 162) | 3.7 percentage of participants |
| Oxycodone Hydrochloride (HCl) and Naltrexone HCl | Percentage of Participants With Current Opioid Misuse Measure (COMM) Score of 9 or Above | Month 12 or early termination (n= 333) | 15.3 percentage of participants |
Other Pre-specified
Percentage of Participants With Response to Urine Drug Test
Participants with a positive urine drug test for illicit drug substances (marijuana, cocaine, amphetamines, methamphetamines, phencyclidine, and ecstasy), or unexpected drug substances (those other than reported by the participant as therapeutic concomitant medications such as opiates and methadone), or a negative urine test for the expected opioid (oxycodone) was assessed.
Time frame: Screening, Week 4, Month 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 or early termination
Population: Safety analysis set. Here N (number of participants analyzed) signifies those participants who were evaluable for this measure and n signifies those participants who were evaluable at specified time point.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Oxycodone Hydrochloride (HCl) and Naltrexone HCl | Percentage of Participants With Response to Urine Drug Test | Screening (n= 393) | 86.8 percentage of participants |
| Oxycodone Hydrochloride (HCl) and Naltrexone HCl | Percentage of Participants With Response to Urine Drug Test | Week 4 (n= 302) | 41.7 percentage of participants |
| Oxycodone Hydrochloride (HCl) and Naltrexone HCl | Percentage of Participants With Response to Urine Drug Test | Month 2 (n= 251) | 43.0 percentage of participants |
| Oxycodone Hydrochloride (HCl) and Naltrexone HCl | Percentage of Participants With Response to Urine Drug Test | Month 3 (n= 222) | 43.2 percentage of participants |
| Oxycodone Hydrochloride (HCl) and Naltrexone HCl | Percentage of Participants With Response to Urine Drug Test | Month 4 (n= 211) | 39.3 percentage of participants |
| Oxycodone Hydrochloride (HCl) and Naltrexone HCl | Percentage of Participants With Response to Urine Drug Test | Month 5 (n= 198) | 41.4 percentage of participants |
| Oxycodone Hydrochloride (HCl) and Naltrexone HCl | Percentage of Participants With Response to Urine Drug Test | Month 6 (n= 190) | 44.2 percentage of participants |
| Oxycodone Hydrochloride (HCl) and Naltrexone HCl | Percentage of Participants With Response to Urine Drug Test | Month 7 (n= 184) | 41.8 percentage of participants |
| Oxycodone Hydrochloride (HCl) and Naltrexone HCl | Percentage of Participants With Response to Urine Drug Test | Month 8 (n= 179) | 44.1 percentage of participants |
| Oxycodone Hydrochloride (HCl) and Naltrexone HCl | Percentage of Participants With Response to Urine Drug Test | Month 9 (n= 174) | 44.8 percentage of participants |
| Oxycodone Hydrochloride (HCl) and Naltrexone HCl | Percentage of Participants With Response to Urine Drug Test | Month 10 (n= 167) | 44.3 percentage of participants |
| Oxycodone Hydrochloride (HCl) and Naltrexone HCl | Percentage of Participants With Response to Urine Drug Test | Month 11 (n= 161) | 50.3 percentage of participants |
| Oxycodone Hydrochloride (HCl) and Naltrexone HCl | Percentage of Participants With Response to Urine Drug Test | Month 12 or early termination (n= 343) | 57.1 percentage of participants |
Other Pre-specified
Time to Stabilization of Study Medication
Stabilization was considered to have occurred when: total daily dose of oxycodone and naltrexone remained unchanged for greater than or equal to (\>=) 3 consecutive days, daily acetaminophen used remained at 1 gram or less and immediate-release oxycodone was not being used as a rescue medication. Days to stabilization = date of stabilization - date of first dose + 1.
Time frame: Baseline up to Month 12
Population: Safety analysis set included all enrolled participants who had at least 1 dose of oxycodone HCl and naltrexone HCl extended-release capsules. Here N (number of participants analyzed) signifies those participants who were evaluable for this measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Oxycodone Hydrochloride (HCl) and Naltrexone HCl | Time to Stabilization of Study Medication | 11.0 days |