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

• ClinicalTrials.gov Identifier: NCT01428583
• Recruitment Status: Completed
• First Posted: September 5, 2011
• Results First Posted: November 21, 2016
• Last Update Posted: November 21, 2016
• Sponsor: Pfizer
• Information provided by (Responsible Party): Pfizer

Tracking Information

• First Submitted Date: September 2, 2011
• First Posted Date: September 5, 2011
• Results First Submitted Date: September 28, 2016
• Results First Posted Date: November 21, 2016
• Last Update Posted Date: November 21, 2016
• Study Start Date: December 2010
• Actual Primary Completion Date: May 2012 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: September 28, 2016)

Number of Participants With Treatment-Emergent Adverse Events (AEs) and Adverse Reactions [ Time Frame: 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.

Original Primary Outcome Measures (submitted: September 2, 2011)

• Subjects with treatment-emergent adverse events [ Time Frame: up to 12 months ]
• Subjects with adverse reactions (AEs assessed by the investigator as treatment-related) [ Time Frame: up to 12 months ]

Current Secondary Outcome Measures (submitted: September 28, 2016)

• Number of Participants With Treatment Emergent (TE) Adverse Events (AEs) Based on Intensity [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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.

Original Secondary Outcome Measures (submitted: September 2, 2011)

• Subjects with treatment-emergent AEs by maximum intensity [ Time Frame: up to 12 months ]
• Mean change from baseline to 12 months or early discontinuation in heart rate [ Time Frame: baseline to 12 months or early discontinuation ]
• Mean change from baseline to 12 months or early discontinuation in systolic blood pressure [ Time Frame: baseline to 12 months or early discontinuation ]
• Mean change from baseline to 12 months or early discontinuation in diastolic blood pressure [ Time Frame: baseline to 12 months or early discontinuation ]
• Mean change from baseline to 12 months or early discontinuation in respiratory rate [ Time Frame: baseline to 12 months or early discontinuation ]
• Mean change from baseline to 12 months or early discontinuation in heart rate from 12-lead ECG [ Time Frame: baseline to 12 months or early discontinuation ]
• Mean change from baseline to 12 months or early discontinuation in QRS interval from 12-lead ECG [ Time Frame: baseline to 12 months or early discontinuation ]
• Mean change from baseline to 12 months or early discontinuation in QT interval from 12-lead ECG [ Time Frame: baseline to 12 months or early discontinuation ]
• Mean change from baseline to 12 months or early discontinuation in QTc interval (Bazett's correction) from 12-lead ECG [ Time Frame: baseline to 12 months or early discontinuation ]
• Mean change from baseline to 12 months or early discontinuation in PR interval from 12-lead ECG [ Time Frame: baseline to 12 months or early discontinuation ]
• Subjects with treatment-emergent abnormal clinically significant results from 12-lead ECG at 12 months or early discontinuation [ Time Frame: 12 months or early discontinuation ]
• Mean change from baseline to 12 months or early discontinuation from 12-lead ECG [ Time Frame: baseline to 12 months or early discontinuation ]
• Mean change from baseline to 12 months or early discontinuation in alanine aminotransferase (ALT) [ Time Frame: baseline to 12 months or early discontinuation ]
• Mean change from baseline to 12 months or early discontinuation in alkaline phosphatase [ Time Frame: baseline to 12 months or early discontinuation ]
• Mean change from baseline to 12 months or early discontinuation in aspartate aminotransferase (AST) [ Time Frame: baseline to 12 months or early discontinuation ]
• Mean change from baseline to 12 months or early discontinuation in total bilirubin [ Time Frame: baseline to 12 months or early discontinuation ]
• Mean change from baseline to 12 months or early discontinuation in blood urea nitrogen [ Time Frame: baseline to 12 months or early discontinuation ]
• Mean change from baseline to 12 months or early discontinuation in serum creatinine [ Time Frame: baseline to 12 months or early discontinuation ]
• Mean change from baseline to 12 months or early discontinuation in creatine phosphokinase [ Time Frame: baseline to 12 months or early discontinuation ]
• Mean change from baseline to 12 months or early discontinuation in potassium [ Time Frame: baseline to 12 months or early discontinuation ]
• Mean change from baseline to 12 months or early discontinuation in sodium [ Time Frame: baseline to 12 months or early discontinuation ]
• Mean change from baseline to 12 months or early discontinuation in hematocrit [ Time Frame: baseline to 12 months or early discontinuation ]
• Mean change from baseline to 12 months or early discontinuation in hemoglobin [ Time Frame: baseline to 12 months or early discontinuation ]
• Mean change from baseline to 12 months or early discontinuation in platelet count [ Time Frame: baseline to 12 months or early discontinuation ]
• Mean change from baseline to 12 months or early discontinuation in red blood cell count [ Time Frame: baseline to 12 months or early discontinuation ]
• Mean change from baseline to 12 months or early discontinuation in white blood cell count [ Time Frame: baseline to 12 months or early discontinuation ]
• Subjects with clinical opiate withdrawal by intensity, determined by Clinical Opiate Withdrawal Scale (COWS) assessment [ Time Frame: 12 months or early discontinuation ]
• Mean scores of clinical opiate withdrawal determined by Subjective Opiate Withdrawal Scale (SOWS) assessment [ Time Frame: 12 months or early discontinuation ]
• Mean change from baseline to 1 week in 'worst pain' score [ Time Frame: baseline to 1 week ]
• Mean change from baseline to 4 weeks in 'worst pain' score [ Time Frame: baseline to 4 weeks ]
• Mean change from baseline to 2 months in 'worst pain' score [ Time Frame: baseline to 2 months ]
• Mean change from baseline to 3 months in 'worst pain' score [ Time Frame: baseline to 3 months ]
• Mean change from baseline to 4 months in 'worst pain' score [ Time Frame: baseline to 4 months ]
• Mean change from baseline to 5 months in 'worst pain' score [ Time Frame: baseline to 5 months ]
• Mean change from baseline to 6 months in 'worst pain' score [ Time Frame: baseline to 6 months ]
• Mean change from baseline to 7 months in 'worst pain' score [ Time Frame: baseline to 7 months ]
• Mean change from baseline to 8 months in 'worst pain' score [ Time Frame: baseline to 8 months ]
• Mean change from baseline to 9 months in 'worst pain' score [ Time Frame: baseline to 9 months ]
• Mean change from baseline to 10 months in 'worst pain' score [ Time Frame: baseline to 10 months ]
• Mean change from baseline to 11 months in 'worst pain' score [ Time Frame: baseline to 11 months ]
• Mean change from baseline to 12 months in 'worst pain' score [ Time Frame: baseline to 12 months ]
• Mean change from baseline to 12 months or early discontinuation in 'worst pain' score [ Time Frame: baseline to 12 months or early discontinuation ]
• Mean change from baseline to 1 week in 'least pain' score [ Time Frame: baseline to 1 week ]
• Mean change from baseline to 4 weeks in 'least pain' score [ Time Frame: baseline to 4 weeks ]
• Mean change from baseline to 2 months in 'least pain' score [ Time Frame: baseline to 2 months ]
• Mean change from baseline to 3 months in 'least pain' score [ Time Frame: baseline to 3 months ]
• Mean change from baseline to 4 months in 'least pain' score [ Time Frame: baseline to 4 months ]
• Mean change from baseline to 5 months in 'least pain' score [ Time Frame: baseline to 5 months ]
• Mean change from baseline to 6 months in 'least pain' score [ Time Frame: baseline to 6 months ]
• Mean change from baseline to 7 months in 'least pain' score [ Time Frame: baseline to 7 months ]
• Mean change from baseline to 8 months in 'least pain' score [ Time Frame: baseline to 8 months ]
• Mean change from baseline to 9 months in 'least pain' score [ Time Frame: baseline to 9 months ]
• Mean change from baseline to 10 months in 'least pain' score [ Time Frame: baseline to 10 months ]
• Mean change from baseline to 11 months in 'least pain' score [ Time Frame: baseline to 11 months ]
• Mean change from baseline to 12 months in 'least pain' score [ Time Frame: baseline to 12 months ]
• Mean change from baseline to 12 months or early discontinuation in 'least pain' score [ Time Frame: baseline to 12 months or early discontinuation ]
• Mean change from baseline to 1 week in 'average pain' score [ Time Frame: baseline to 1 week ]
• Mean change from baseline to 4 weeks in 'average pain' score [ Time Frame: baseline to 4 weeks ]
• Mean change from baseline to 2 months in 'average pain' score [ Time Frame: baseline to 2 months ]
• Mean change from baseline to 3 months in 'average pain' score [ Time Frame: baseline to 3 months ]
• Mean change from baseline to 4 months in 'average pain' score [ Time Frame: baseline to 4 months ]
• Mean change from baseline to 5 months in 'average pain' score [ Time Frame: baseline to 5 months ]
• Mean change from baseline to 6 months in 'average pain' score [ Time Frame: baseline to 6 months ]
• Mean change from baseline to 7 months in 'average pain' score [ Time Frame: baseline to 7 months ]
• Mean change from baseline to 8 months in 'average pain' score [ Time Frame: baseline to 8 months ]
• Mean change from baseline to 9 months in 'average pain' score [ Time Frame: baseline to 9 months ]
• Mean change from baseline to 10 months in 'average pain' score [ Time Frame: baseline to 10 months ]
• Mean change from baseline to 11 months in 'average pain' score [ Time Frame: baseline to 11 months ]
• Mean change from baseline to 12 months in 'average pain' score [ Time Frame: baseline to 12 months ]
• Mean change from baseline to 12 months or early discontinuation in 'average pain' score [ Time Frame: baseline to 12 months or early discontinuation ]
• Mean change from baseline to 1 week in 'pain right now' score [ Time Frame: baseline to 1 week ]
• Mean change from baseline to 4 weeks in 'pain right now' score [ Time Frame: baseline to 4 weeks ]
• Mean change from baseline to 2 months in 'pain right now' score [ Time Frame: baseline to 2 months ]
• Mean change from baseline to 3 months in 'pain right now' score [ Time Frame: baseline to 3 months ]
• Mean change from baseline to 4 months in 'pain right now' score [ Time Frame: baseline to 4 months ]
• Mean change from baseline to 5 months in 'pain right now' score [ Time Frame: baseline to 5 months ]
• Mean change from baseline to 6 months in 'pain right now' score [ Time Frame: baseline to 6 months ]
• Mean change from baseline to 7 months in 'pain right now' score [ Time Frame: baseline to 7 months ]
• Mean change from baseline to 8 months in 'pain right now' score [ Time Frame: baseline to 8 months ]
• Mean change from baseline to 9 months in 'pain right now' score [ Time Frame: baseline to 9 months ]
• Mean change from baseline to 10 months in 'pain right now' score [ Time Frame: baseline to 10 months ]
• Mean change from baseline to 11 months in 'pain right now' score [ Time Frame: baseline to 11 months ]
• Mean change from baseline to 12 months in 'pain right now' score [ Time Frame: baseline to 12 months ]
• Mean change from baseline to 12 months or early discontinuation in 'pain right now' score [ Time Frame: baseline to 12 months or early discontinuation ]
• Subjects rating satisfied or very satisfied in global assessment of treatment satisfaction at 1 week [ Time Frame: 1 week ]
• Subjects rating satisfied or very satisfied in global assessment of treatment satisfaction at 4 weeks [ Time Frame: 4 weeks ]
• Subjects rating satisfied or very satisfied in global assessment of treatment satisfaction at 2 months [ Time Frame: 2 months ]
• Subjects rating satisfied or very satisfied in global assessment of treatment satisfaction at 3 months [ Time Frame: 3 months ]
• Subjects rating satisfied or very satisfied in global assessment of treatment satisfaction at 4 months [ Time Frame: 4 months ]
• Subjects rating satisfied or very satisfied in global assessment of treatment satisfaction at 5 months [ Time Frame: 5 months ]
• Subjects rating satisfied or very satisfied in global assessment of treatment satisfaction at 6 months [ Time Frame: 6 months ]
• Subjects rating satisfied or very satisfied in global assessment of treatment satisfaction at 7 months [ Time Frame: 7 months ]
• Subjects rating satisfied or very satisfied in global assessment of treatment satisfaction at 8 months [ Time Frame: 8 months ]
• Subjects rating satisfied or very satisfied in global assessment of treatment satisfaction at 9 months [ Time Frame: 9 months ]
• Subjects rating satisfied or very satisfied in global assessment of treatment satisfaction at 10 months [ Time Frame: 10 months ]
• Subjects rating satisfied or very satisfied in global assessment of treatment satisfaction at 11 months [ Time Frame: 11 months ]
• Subjects rating satisfied or very satisfied in global assessment of treatment satisfaction at 12 months [ Time Frame: 12 months ]
• Subjects rating satisfied or very satisfied in global assessment of treatment satisfaction at 12 months or early discontinuation [ Time Frame: 12 months or early discontinuation ]
• Mean daily dosage of immediate-release oxycodone as rescue medication during week 1 [ Time Frame: week 1 ]
• Mean daily dosage of immediate-release oxycodone as rescue medication during week 2 [ Time Frame: week 2 ]
• Mean daily dosage of immediate-release oxycodone as rescue medication during week 3 [ Time Frame: week 3 ]
• Mean daily dosage of immediate-release oxycodone as rescue medication during week 4 [ Time Frame: week 4 ]
• Mean number of acetaminophen tablets as rescue medication during week 1 [ Time Frame: week 1 ]
• Mean weekly number of acetaminophen tablets as rescue medication during first 4 weeks [ Time Frame: week 1 to week 4 ]
• Mean weekly number of acetaminophen tablets as rescue medication during month 2 [ Time Frame: month 2 ]
• Mean weekly number of acetaminophen tablets as rescue medication during month 3 [ Time Frame: month 3 ]
• Mean weekly number of acetaminophen tablets as rescue medication during month 4 [ Time Frame: month 4 ]
• Mean weekly number of acetaminophen tablets as rescue medication during month 5 [ Time Frame: month 5 ]
• Mean weekly number of acetaminophen tablets as rescue medication during month 6 [ Time Frame: month 6 ]
• Mean weekly number of acetaminophen tablets as rescue medication during month 7 [ Time Frame: month 7 ]
• Mean weekly number of acetaminophen tablets as rescue medication during month 8 [ Time Frame: month 8 ]
• Mean weekly number of acetaminophen tablets as rescue medication during month 9 [ Time Frame: month 9 ]
• Mean weekly number of acetaminophen tablets as rescue medication during month 10 [ Time Frame: month 10 ]
• Mean weekly number of acetaminophen tablets as rescue medication during month 11 [ Time Frame: month 11 ]
• Mean weekly number of acetaminophen tablets as rescue medication during month 12 [ Time Frame: month 12 ]
• Mean daily dose of study drug during week 1 [ Time Frame: week 1 ]
• Mean daily dose of study drug during first 4 weeks [ Time Frame: week 1 to week 4 ]
• Mean daily dose of study drug during month 2 [ Time Frame: month 2 ]
• Mean daily dose of study drug during month 3 [ Time Frame: month 3 ]
• Mean daily dose of study drug during month 4 [ Time Frame: month 4 ]
• Mean daily dose of study drug during month 5 [ Time Frame: month 5 ]
• Mean daily dose of study drug during month 6 [ Time Frame: month 6 ]
• Mean daily dose of study drug during month 7 [ Time Frame: month 7 ]
• Mean daily dose of study drug during month 8 [ Time Frame: month 8 ]
• Mean daily dose of study drug during month 9 [ Time Frame: month 9 ]
• Mean daily dose of study drug during month 10 [ Time Frame: month 10 ]
• Mean daily dose of study drug during month 11 [ Time Frame: month 11 ]
• Mean daily dose of study drug during month 12 [ Time Frame: month 12 ]
• Mean duration of exposure to study drug [ Time Frame: 12 months ]
• Mean time to stabilization of the total daily dose of study drug [ Time Frame: up to 12 months ]
• Mean observed steady-state plasma concentration (Cobs) of oxycodone at 1 week [ Time Frame: 1 week ]
• Mean Cobs of oxycodone at 4 weeks [ Time Frame: 4 weeks ]
• Mean Cobs of oxycodone at 2 months [ Time Frame: 2 months ]
• Mean Cobs of oxycodone at 3 months [ Time Frame: 3 months ]
• Mean Cobs of oxycodone at 6 months [ Time Frame: 6 months ]
• Mean Cobs of oxycodone at 9 months [ Time Frame: 9 months ]
• Mean Cobs of oxycodone at 12 months [ Time Frame: 12 months ]
• Mean Cobs of oxycodone at 12 months or early discontinuation [ Time Frame: 12 months or early discontinuation ]
• Mean Cobs of noroxycodone at 1 week [ Time Frame: 1 week ]
• Mean Cobs of noroxycodone at 4 weeks [ Time Frame: 4 weeks ]
• Mean Cobs of noroxycodone at 2 months [ Time Frame: 2 months ]
• Mean Cobs of noroxycodone at 3 months [ Time Frame: 3 months ]
• Mean Cobs of noroxycodone at 6 months [ Time Frame: 6 months ]
• Mean Cobs of noroxycodone at 9 months [ Time Frame: 9 months ]
• Mean Cobs of noroxycodone at 12 months [ Time Frame: 12 months ]
• Mean Cobs of noroxycodone at 12 months or early discontinuation [ Time Frame: 12 months or early discontinuation ]
• Mean Cobs of naltrexone at 1 week [ Time Frame: 1 week ]
• Mean Cobs of naltrexone at 4 weeks [ Time Frame: 4 weeks ]
• Mean Cobs of naltrexone at 2 months [ Time Frame: 2 months ]
• Mean Cobs of naltrexone at 3 months [ Time Frame: 3 months ]
• Mean Cobs of naltrexone at 6 months [ Time Frame: 6 months ]
• Mean Cobs of naltrexone at 9 months [ Time Frame: 9 months ]
• Mean Cobs of naltrexone at 12 months [ Time Frame: 12 months ]
• Mean Cobs of naltrexone at 12 months or early discontinuation [ Time Frame: 12 months or early discontinuation ]
• Mean Cobs of 6-β-naltrexol at 1 week [ Time Frame: 1 week ]
• Mean Cobs of 6-β-naltrexol at 4 weeks [ Time Frame: 4 weeks ]
• Mean Cobs of 6-β-naltrexol at 2 months [ Time Frame: 2 months ]
• Mean Cobs of 6-β-naltrexol at 3 months [ Time Frame: 3 months ]
• Mean Cobs of 6-β-naltrexol at 6 months [ Time Frame: 6 months ]
• Mean Cobs of 6-β-naltrexol at 9 months [ Time Frame: 9 months ]
• Mean Cobs of 6-β-naltrexol at 12 months [ Time Frame: 12 months ]
• Mean Cobs of 6-β-naltrexol at 12 months or early discontinuation [ Time Frame: 12 months or early discontinuation ]
• Subjects with a Current Opioid Misuse Measure (COMM) score of 9 or above [ Time Frame: up to 12 months ]
• Subjects with a positive urine drug test for illicit drug substances or unaccounted opioids, or a negative urine test for the expected opioid oxycodone [ Time Frame: up to 12 months ]

Current Other Pre-specified Outcome Measures (submitted: September 28, 2016)

• Observed Steady-state Plasma Concentrations (Cobs) of Oxycodone [ Time Frame: Week 1, 4, Month 2, 3, 6, 9, 12 or early termination ]
• Observed Steady-state Plasma Concentrations (Cobs) of Noroxycodone [ Time Frame: 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 [ Time Frame: Week 1, 4, Month 2, 3, 6, 9, 12 or early termination ]
• Observed Steady-state Plasma Concentrations (Cobs) of 6-Beta-naltrexol [ Time Frame: Week 1, 4, Month 2, 3, 6, 9, 12 or early termination ]
  6-Beta-naltrexol was a metabolite of naltrexone.
• Time to Stabilization of Study Medication [ Time Frame: 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 [ Time Frame: 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) [ 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) ]
• Number of Participants With Rescue Medication (Acetaminophen Tablets) [ 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) ]
  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 [ Time Frame: 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.
• Percentage of Participants With Current Opioid Misuse Measure (COMM) Score of 9 or Above [ Time Frame: 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.
• Mean Daily Dose of Immediate-release Oxycodone as Rescue Medication [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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.

• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Safety Study of Oxycodone Hydrochloride and Naltrexone Hydrochloride Extended-Release Capsules in Subjects With Moderate to Severe Chronic Noncancer Pain
• Official Title: A Multicenter, 12-month, Open-label, Single-arm, Safety Study Of Oxycodone Hydrochloride And Naltrexone Hydrochloride Extended-release Capsules In Subjects With Moderate To Severe Chronic Noncancer Pain
• 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Masking: None (Open Label); Primary Purpose: Supportive Care
• Condition: Chronic Noncancer Pain

Intervention

Drug: oxycodone 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.)

Other Name: ALO-02

Study Arms

Experimental: oxycodone HCl and naltrexone HCl extended-release capsules

Intervention: Drug: oxycodone HCl and naltrexone HCl extended-release capsules

Publications *

• Gimbel JS, Rauck RL, Bass A, Wilson J, Pixton G, Malhotra B, Wilson G, Wolfram G. Effects of naltrexone exposure observed in two phase three studies with ALO-02, an extended-release oxycodone surrounding sequestered naltrexone. J Opioid Manag. 2019 Sep/Oct;15(5):417-427. doi: 10.5055/jom.2019.0530.
• Wilson JG, Bass A, Pixton GC, Wolfram G, Rauck RL. Safety and tolerability of ALO-02 (oxycodone hydrochloride and sequestered naltrexone hydrochloride) extended-release capsules in older patients: a pooled analysis of two clinical trials. Curr Med Res Opin. 2020 Jan;36(1):91-99. doi: 10.1080/03007995.2019.1661679. Epub 2019 Sep 17.
• Arora S, Setnik B, Michael D, Hudson JD, Clemmer R, Meisner P, Pixton GC, Goli V, Sommerville KW. A multicenter, 12-month, open-label, single-arm safety study of oxycodone-hydrochloride/naltrexone-hydrochloride extended-release capsules (ALO-02) in patients with moderate-to-severe chronic noncancer pain. J Opioid Manag. 2014 Nov-Dec;10(6):423-36. doi: 10.5055/jom.2014.0239.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: September 2, 2011): 395
• Original Estimated Enrollment: Same as current
• Actual Study Completion Date: May 2012
• Actual Primary Completion Date: May 2012 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT01428583
• Other Study ID Numbers: ALO-02-10-3001; B4531001 ( Other Identifier: Alias Study Number )
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Pfizer
• Original Responsible Party: Alpharma Pharmaceuticals LLC, a subsidiary of Pfizer Inc.
• Current Study Sponsor: Pfizer
• Original Study Sponsor: Alpharma Pharmaceuticals LLC, a subsidiary of Pfizer Inc.
• Collaborators: Not Provided

Investigators

• Study Director: Pfizer CT.gov Call Center; Pfizer

• PRS Account: Pfizer
• Verification Date: June 2016