Trial Outcomes & Findings for Safety Study of Oxycodone Hydrochloride and Naltrexone Hydrochloride Extended-Release Capsules in Subjects With Moderate to Severe Chronic Noncancer Pain (NCT NCT01428583)

Last Updated: 2016-11-21

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

395 participants

Primary outcome timeframe

Baseline up to end of study (2 weeks post-end of month 12)

Results posted on

2016-11-21

Participant Flow

Participant milestones

Participant milestones
Measure	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.
Overall Study STARTED	395
Overall Study COMPLETED	158
Overall Study NOT COMPLETED	237

Reasons for withdrawal

Reasons for withdrawal
Measure	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.
Overall Study Adverse Event	75
Overall Study Withdrawal by Subject	51
Overall Study Lack of Efficacy	37
Overall Study Lost to Follow-up	17
Overall Study Death	1
Overall Study Pregnancy	1
Overall Study Protocol Violation	1
Overall Study Physician Decision	12
Overall Study Non-compliant	25
Overall Study Confirmed positive urine drug test	8
Overall Study Sponsor's request	3
Overall Study Other	6

Baseline Characteristics

Safety Study of Oxycodone Hydrochloride and Naltrexone Hydrochloride Extended-Release Capsules in Subjects With Moderate to Severe Chronic Noncancer Pain

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Oxycodone Hydrochloride (HCl) and Naltrexone HCl n=395 Participants 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.
Age, Continuous	53.8 years STANDARD_DEVIATION 12.10 • n=5 Participants
Sex: Female, Male Female	203 Participants n=5 Participants
Sex: Female, Male Male	192 Participants n=5 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Oxycodone Hydrochloride (HCl) and Naltrexone HCl n=395 Participants 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.
Number of Participants With Treatment-Emergent Adverse Events (AEs) and Adverse Reactions Adverse event (all causalities)	343 participants
Number of Participants With Treatment-Emergent Adverse Events (AEs) and Adverse Reactions Adverse reaction	207 participants

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Oxycodone Hydrochloride (HCl) and Naltrexone HCl n=395 Participants 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.
Number of Participants With Treatment Emergent (TE) Adverse Events (AEs) Based on Intensity Mild	94 participants
Number of Participants With Treatment Emergent (TE) Adverse Events (AEs) Based on Intensity Moderate	202 participants
Number of Participants With Treatment Emergent (TE) Adverse Events (AEs) Based on Intensity Severe	47 participants

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Oxycodone Hydrochloride (HCl) and Naltrexone HCl n=395 Participants 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.
Percentage of Participants With Clinical Opiate Withdrawal Scale (COWS) Score Mild (score 5-12)	13.2 percentage of participants
Percentage of Participants With Clinical Opiate Withdrawal Scale (COWS) Score Moderate (score 13-24)	0.0 percentage of participants
Percentage of Participants With Clinical Opiate Withdrawal Scale (COWS) Score Moderately severe (score 25-36)	0.3 percentage of participants
Percentage of Participants With Clinical Opiate Withdrawal Scale (COWS) Score Severe (score greater than 36)	0.0 percentage of participants

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Oxycodone Hydrochloride (HCl) and Naltrexone HCl n=395 Participants 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.
Subjective Opiate Withdrawal Scale (SOWS) Score Baseline (n= 395)	5.4 units on a scale Standard Deviation 5.49
Subjective Opiate Withdrawal Scale (SOWS) Score Week 1 (n= 362)	4.6 units on a scale Standard Deviation 6.15
Subjective Opiate Withdrawal Scale (SOWS) Score Week 4 (n= 307)	3.6 units on a scale Standard Deviation 4.32
Subjective Opiate Withdrawal Scale (SOWS) Score Month 2 (n= 252)	3.6 units on a scale Standard Deviation 4.70
Subjective Opiate Withdrawal Scale (SOWS) Score Month 3 (n= 221)	3.3 units on a scale Standard Deviation 4.53
Subjective Opiate Withdrawal Scale (SOWS) Score Month 4 (n= 210)	2.9 units on a scale Standard Deviation 4.30
Subjective Opiate Withdrawal Scale (SOWS) Score Month 5 (n= 198)	3.2 units on a scale Standard Deviation 4.56
Subjective Opiate Withdrawal Scale (SOWS) Score Month 6 (n= 190)	2.5 units on a scale Standard Deviation 3.27
Subjective Opiate Withdrawal Scale (SOWS) Score Month 7 (n= 185)	2.4 units on a scale Standard Deviation 4.07
Subjective Opiate Withdrawal Scale (SOWS) Score Month 8 (n= 180)	2.5 units on a scale Standard Deviation 3.74
Subjective Opiate Withdrawal Scale (SOWS) Score Month 9 (n= 174)	2.4 units on a scale Standard Deviation 4.08
Subjective Opiate Withdrawal Scale (SOWS) Score Month 10 (n= 167)	2.2 units on a scale Standard Deviation 3.25
Subjective Opiate Withdrawal Scale (SOWS) Score Month 11 (n= 162)	2.3 units on a scale Standard Deviation 3.53
Subjective Opiate Withdrawal Scale (SOWS) Score Month 12 (n= 154)	2.4 units on a scale Standard Deviation 4.09

OTHER_PRE_SPECIFIED outcome

Timeframe: 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.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: 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.

Noroxycodone was a metabolite of Oxycodone.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: 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.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: 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.

6-Beta-naltrexol was a metabolite of naltrexone.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Oxycodone Hydrochloride (HCl) and Naltrexone HCl n=246 Participants 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.
Time to Stabilization of Study Medication	11.0 days Interval 3.0 to 133.0

OTHER_PRE_SPECIFIED outcome

Timeframe: 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.

Duration of exposure to study medication during the course of the study was assessed.

Outcome measures

Outcome measures
Measure	Oxycodone Hydrochloride (HCl) and Naltrexone HCl n=395 Participants 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.
Duration of Exposure to Study Medication	171.0 days Interval 1.0 to 406.0

OTHER_PRE_SPECIFIED outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Oxycodone Hydrochloride (HCl) and Naltrexone HCl n=395 Participants 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.
Mean Daily Dose of Study Medication (Oxycodone Component) Baseline-less than (<) Week 1 (n= 378)	38.6 milligram/day Standard Deviation 81.27
Mean Daily Dose of Study Medication (Oxycodone Component) Week 1-<4 (n= 344)	51.7 milligram/day Standard Deviation 35.53
Mean Daily Dose of Study Medication (Oxycodone Component) Week 4-<Month 2 (n= 292)	62.8 milligram/day Standard Deviation 42.65
Mean Daily Dose of Study Medication (Oxycodone Component) Month 2-< 3 (n= 238)	66.1 milligram/day Standard Deviation 40.35
Mean Daily Dose of Study Medication (Oxycodone Component) Month 3-<4 (n= 217)	68.0 milligram/day Standard Deviation 40.36
Mean Daily Dose of Study Medication (Oxycodone Component) Month 4-< 5 (n= 205)	68.6 milligram/day Standard Deviation 41.49
Mean Daily Dose of Study Medication (Oxycodone Component) Month 5-<6 (n= 193)	71.5 milligram/day Standard Deviation 43.58
Mean Daily Dose of Study Medication (Oxycodone Component) Month 6-<7 (n= 183)	73.1 milligram/day Standard Deviation 43.22
Mean Daily Dose of Study Medication (Oxycodone Component) Month 7- <8 (n= 183)	76.7 milligram/day Standard Deviation 43.76
Mean Daily Dose of Study Medication (Oxycodone Component) Month 8-<9 (n= 177)	77.7 milligram/day Standard Deviation 45.67
Mean Daily Dose of Study Medication (Oxycodone Component) Month 9-<10 (n= 169)	76.5 milligram/day Standard Deviation 44.58
Mean Daily Dose of Study Medication (Oxycodone Component) Month 10- <11 (n= 163)	77.9 milligram/day Standard Deviation 44.45
Mean Daily Dose of Study Medication (Oxycodone Component) Month 11- <12 (n= 160)	76.2 milligram/day Standard Deviation 43.14
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 outcome

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.

Participants had acetaminophen up to 2 grams per day during the treatment period of the study as rescue medication.

Outcome measures

Outcome measures
Measure	Oxycodone Hydrochloride (HCl) and Naltrexone HCl n=387 Participants 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.
Number of Participants With Rescue Medication (Acetaminophen Tablets) Month 2-<3 (n= 252)	124 participants
Number of Participants With Rescue Medication (Acetaminophen Tablets) Baseline-<Week 1 (n= 387)	256 participants
Number of Participants With Rescue Medication (Acetaminophen Tablets) Week 1-<4 (n= 361)	204 participants
Number of Participants With Rescue Medication (Acetaminophen Tablets) Week 4-<Month 2 (n= 305)	167 participants
Number of Participants With Rescue Medication (Acetaminophen Tablets) Month 3-<4 (n= 222)	120 participants
Number of Participants With Rescue Medication (Acetaminophen Tablets) Month 4-<5 (n= 209)	112 participants
Number of Participants With Rescue Medication (Acetaminophen Tablets) Month 5-<6 (n= 199)	104 participants
Number of Participants With Rescue Medication (Acetaminophen Tablets) Month 6-<7 (n= 191)	96 participants
Number of Participants With Rescue Medication (Acetaminophen Tablets) Month 7-<8 (n= 185)	96 participants
Number of Participants With Rescue Medication (Acetaminophen Tablets) Month8-<9 (n= 179)	93 participants
Number of Participants With Rescue Medication (Acetaminophen Tablets) Month 9-<10 (n= 172)	79 participants
Number of Participants With Rescue Medication (Acetaminophen Tablets) Month 10-<11 (n= 167)	80 participants
Number of Participants With Rescue Medication (Acetaminophen Tablets) Month 11-<12 (n= 163)	85 participants
Number of Participants With Rescue Medication (Acetaminophen Tablets) Month 12-<End of study (n= 95)	30 participants

OTHER_PRE_SPECIFIED outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Oxycodone Hydrochloride (HCl) and Naltrexone HCl n=395 Participants 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.
Percentage of Participants With Response to Urine Drug Test Screening (n= 393)	86.8 percentage of participants
Percentage of Participants With Response to Urine Drug Test Week 4 (n= 302)	41.7 percentage of participants
Percentage of Participants With Response to Urine Drug Test Month 2 (n= 251)	43.0 percentage of participants
Percentage of Participants With Response to Urine Drug Test Month 3 (n= 222)	43.2 percentage of participants
Percentage of Participants With Response to Urine Drug Test Month 4 (n= 211)	39.3 percentage of participants
Percentage of Participants With Response to Urine Drug Test Month 5 (n= 198)	41.4 percentage of participants
Percentage of Participants With Response to Urine Drug Test Month 6 (n= 190)	44.2 percentage of participants
Percentage of Participants With Response to Urine Drug Test Month 7 (n= 184)	41.8 percentage of participants
Percentage of Participants With Response to Urine Drug Test Month 8 (n= 179)	44.1 percentage of participants
Percentage of Participants With Response to Urine Drug Test Month 9 (n= 174)	44.8 percentage of participants
Percentage of Participants With Response to Urine Drug Test Month 10 (n= 167)	44.3 percentage of participants
Percentage of Participants With Response to Urine Drug Test Month 11 (n= 161)	50.3 percentage of participants
Percentage of Participants With Response to Urine Drug Test Month 12 or early termination (n= 343)	57.1 percentage of participants

OTHER_PRE_SPECIFIED outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Oxycodone Hydrochloride (HCl) and Naltrexone HCl n=395 Participants 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.
Percentage of Participants With Current Opioid Misuse Measure (COMM) Score of 9 or Above Baseline (n= 395)	21.3 percentage of participants
Percentage of Participants With Current Opioid Misuse Measure (COMM) Score of 9 or Above Week 4 (n= 302)	8.9 percentage of participants
Percentage of Participants With Current Opioid Misuse Measure (COMM) Score of 9 or Above Month 2 (n= 250)	10.0 percentage of participants
Percentage of Participants With Current Opioid Misuse Measure (COMM) Score of 9 or Above Month 3 (n= 217)	8.3 percentage of participants
Percentage of Participants With Current Opioid Misuse Measure (COMM) Score of 9 or Above Month 4 (n= 208)	6.7 percentage of participants
Percentage of Participants With Current Opioid Misuse Measure (COMM) Score of 9 or Above Month 5 (n= 197)	5.1 percentage of participants
Percentage of Participants With Current Opioid Misuse Measure (COMM) Score of 9 or Above Month 6 (n= 189)	2.6 percentage of participants
Percentage of Participants With Current Opioid Misuse Measure (COMM) Score of 9 or Above Month 7 (n= 185)	3.2 percentage of participants
Percentage of Participants With Current Opioid Misuse Measure (COMM) Score of 9 or Above Month 8 (n= 181)	5.0 percentage of participants
Percentage of Participants With Current Opioid Misuse Measure (COMM) Score of 9 or Above Month 9 (n= 174)	5.7 percentage of participants
Percentage of Participants With Current Opioid Misuse Measure (COMM) Score of 9 or Above Month 10 (n= 167)	4.8 percentage of participants
Percentage of Participants With Current Opioid Misuse Measure (COMM) Score of 9 or Above Month 11 (n= 162)	3.7 percentage of participants
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 outcome

Timeframe: 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.

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.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Oxycodone Hydrochloride (HCl) and Naltrexone HCl n=387 Participants 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.
Participants Global Assessment of Treatment Satisfaction Week 1 (n= 361)	3.3 unit on a scale Standard Deviation 1.03
Participants Global Assessment of Treatment Satisfaction Week 4 (n= 304)	3.8 unit on a scale Standard Deviation 0.99
Participants Global Assessment of Treatment Satisfaction Month 2 (n= 251)	3.9 unit on a scale Standard Deviation 0.94
Participants Global Assessment of Treatment Satisfaction Month 3 (n= 220)	4.1 unit on a scale Standard Deviation 0.88
Participants Global Assessment of Treatment Satisfaction Month 4 (n= 209)	4.1 unit on a scale Standard Deviation 0.93
Participants Global Assessment of Treatment Satisfaction Month 5 (n= 197)	4.2 unit on a scale Standard Deviation 0.90
Participants Global Assessment of Treatment Satisfaction Month 6 (n= 190)	4.2 unit on a scale Standard Deviation 0.89
Participants Global Assessment of Treatment Satisfaction Month 7 (n= 185)	4.2 unit on a scale Standard Deviation 0.81
Participants Global Assessment of Treatment Satisfaction Month 8 (n= 181)	4.2 unit on a scale Standard Deviation 0.81
Participants Global Assessment of Treatment Satisfaction Month 9 (n= 174)	4.2 unit on a scale Standard Deviation 0.96
Participants Global Assessment of Treatment Satisfaction Month 10 (n= 167)	4.3 unit on a scale Standard Deviation 0.73
Participants Global Assessment of Treatment Satisfaction Month 11 (n= 162)	4.3 unit on a scale Standard Deviation 0.79
Participants Global Assessment of Treatment Satisfaction Month 12 (n= 154)	4.2 unit on a scale Standard Deviation 1.04
Participants Global Assessment of Treatment Satisfaction End of treatment (n= 372)	3.6 unit on a scale Standard Deviation 1.27

OTHER_PRE_SPECIFIED outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Oxycodone Hydrochloride (HCl) and Naltrexone HCl n=387 Participants 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.
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
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
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
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
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
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
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
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
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 2.40
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
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
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
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
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
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 outcome

Timeframe: Baseline, Week 1, 4, Months 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 12 or Early Termination

Outcome measures

Outcome measures
Measure	Oxycodone Hydrochloride (HCl) and Naltrexone HCl n=387 Participants 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.
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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 outcome

Timeframe: Baseline, Week 1, 4, Months 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 12 or Early Termination

Outcome measures

Outcome measures
Measure	Oxycodone Hydrochloride (HCl) and Naltrexone HCl n=387 Participants 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.
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
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
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
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
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
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
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
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 2.30
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
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
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
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 2.50
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
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
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

Adverse Events

Oxycodone Hydrochloride (HCl) and Naltrexone HCl

Serious events: 26 serious events

Other events: 272 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Oxycodone Hydrochloride (HCl) and Naltrexone HCl n=395 participants at risk 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.
Blood and lymphatic system disorders Hypochromic anaemia	0.25% 1/395 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Cardiac disorders Acute myocardial infarction	0.51% 2/395 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Cardiac disorders Cardiac failure congestive	0.25% 1/395 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Abdominal pain	0.25% 1/395 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Hiatus hernia	0.25% 1/395 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Pancreatitis acute	0.25% 1/395 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Small intestinal obstruction	0.25% 1/395 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
General disorders Chest discomfort	0.25% 1/395 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
General disorders Chest pain	0.25% 1/395 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
General disorders Non-cardiac chest pain	0.51% 2/395 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Hepatobiliary disorders Cholecystitis	0.25% 1/395 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Hepatobiliary disorders Cholelithiasis	0.25% 1/395 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Infections and infestations Infected skin ulcer	0.25% 1/395 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Infections and infestations Osteomyelitis	0.25% 1/395 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Infections and infestations Pneumonia	0.51% 2/395 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Infections and infestations Urinary tract infection	0.25% 1/395 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Investigations Blood pressure increased	0.25% 1/395 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Metabolism and nutrition disorders Hypoglycaemia	0.25% 1/395 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Musculoskeletal and connective tissue disorders Intervertebral disc degeneration	0.25% 1/395 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Musculoskeletal and connective tissue disorders Muscular weakness	0.25% 1/395 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Anal cancer	0.25% 1/395 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Nervous system disorders Cerebrovascular accident	0.25% 1/395 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Nervous system disorders Convulsion	0.51% 2/395 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Psychiatric disorders Mental status changes	0.25% 1/395 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Renal and urinary disorders Nephrolithiasis	0.51% 2/395 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	0.25% 1/395 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Respiratory, thoracic and mediastinal disorders Lung infiltration	0.25% 1/395 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.25% 1/395 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.

Other adverse events

Other adverse events
Measure	Oxycodone Hydrochloride (HCl) and Naltrexone HCl n=395 participants at risk 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.
Gastrointestinal disorders Nausea	25.3% 100/395 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Constipation	21.3% 84/395 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Vomiting	13.9% 55/395 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Diarrhoea	9.1% 36/395 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
General disorders Fatigue	9.1% 36/395 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Infections and infestations Upper respiratory tract infection	6.1% 24/395 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Infections and infestations Influenza	5.1% 20/395 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Musculoskeletal and connective tissue disorders Back pain	6.3% 25/395 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Nervous system disorders Headache	11.6% 46/395 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Nervous system disorders Somnolence	9.4% 37/395 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Nervous system disorders Dizziness	8.6% 34/395 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Psychiatric disorders Anxiety	7.6% 30/395 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Psychiatric disorders Insomnia	5.1% 20/395 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Skin and subcutaneous tissue disorders Hyperhidrosis	6.1% 24/395 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Skin and subcutaneous tissue disorders Pruritus	5.3% 21/395 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.

Additional Information

Pfizer ClinicalTrials.gov Call Center

Pfizer, Inc.

Phone: 1-800-718-1021

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
Publication restrictions are in place

Restriction type: OTHER