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

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

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.

Study Overview

• Status: Completed
• Conditions: Chronic Noncancer Pain
• Intervention / Treatment: Drug: oxycodone HCl and naltrexone HCl extended-release capsules

• Study Type: Interventional
• Enrollment (Actual): 395
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Florida
    • Deland, Florida, United States, 32720
      • Avail Clinical Research, LLC
    • Jacksonville, Florida, United States, 32257
      • Florida Institute of Medical Research
    • Jupiter, Florida, United States, 33458
      • Drug Study Institute
    • Ormond Beach, Florida, United States, 32174
      • Peninsula Research, Inc.
    • Ormond Beach, Florida, United States, 32174
      • Ormond Medical Arts Pharmaceutical Research Center
    • Port Orange, Florida, United States, 32129
      • Accord Clinical Research
    • Sarasota, Florida, United States, 34238
      • Sarasota Pain Medicine Research
    • Tampa, Florida, United States, 33603
      • Clinical Research of West Florida
  • Georgia
    • Atlanta, Georgia, United States, 30327
      • Center for Prospective Outcome Studies, Inc.
    • Marietta, Georgia, United States, 30060
      • Georgia Institute for Clinical Research, LLC
    • Marietta, Georgia, United States, 30060
      • Drug Studies America
  • Kentucky
    • Lexington, Kentucky, United States, 40503
      • The Pain Treatment Center of the Bluegrass
    • Madisonville, Kentucky, United States, 42431
      • Commonwealth BioMedical Research
  • Maryland
    • Owings Mills, Maryland, United States, 21117
      • Crossroads Research
  • Massachusetts
    • Springfield, Massachusetts, United States, 01103
      • DM Clinical Research
  • Minnesota
    • Edina, Minnesota, United States, 55435
      • MAPS Applied Research Center
  • Mississippi
    • Southaven, Mississippi, United States, 38671
      • Mid-South Anesthesia Consultants
  • Missouri
    • Hazelwood, Missouri, United States, 64042
      • Healthcare Research, LLC
  • Montana
    • Missoula, Montana, United States, 59802
      • Montana Neuroscience Institute
  • New Jersey
    • Berlin, New Jersey, United States, 08009
      • Comprehensive Clinical Research
  • New York
    • Hartsdale, New York, United States, 10530
      • Drug Trials America - New York
    • North Syracuse, New York, United States, 13212
      • New York Spine and Wellness Center
    • Williamsville, New York, United States, 14221
      • Upstate Clinical Research Associates
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27103
      • Center for Clinical Research, LLC - Winston-Salem
  • Ohio
    • Columbus, Ohio, United States, 43213
      • Columbus Clinical Research, Inc.
  • Pennsylvania
    • Altoona, Pennsylvania, United States, 16602
      • Allegheny Pain Management, PC
  • Texas
    • Austin, Texas, United States, 78731
      • FutureSearch Trials of Neurology
    • Dallas, Texas, United States, 75230
      • KRK Medical Research
    • Fort Worth, Texas, United States, 76135
      • Benchmark Research - Fort Worth
    • San Antonio, Texas, United States, 78209
      • Quality Research, Inc.
  • Utah
    • Salt Lake City, Utah, United States, 84106
      • Lifetree Clinical Research
  • Virginia
    • Roanoke, Virginia, United States, 24018
      • HypotheTest, LLC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: oxycodone HCl and naltrexone HCl extended-release capsules	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 Names: ALO-02

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Treatment-Emergent Adverse Events (AEs) and Adverse Reactions	An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An AE that was attributed to study drug in a participant who received study drug was defined as an adverse reaction. Treatment-emergent are events between first dose of study drug and up to end of study (2 weeks post-end of month 12) that were absent before treatment or that worsened relative to pretreatment state.	Baseline up to end of study (2 weeks post-end of month 12)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Treatment Emergent (TE) Adverse Events (AEs) Based on Intensity	An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Intensity of adverse event was defined on the basis of severity of an event and was classified as; mild (does not interfere with participant's usual function), moderate (interferes to some extent with participant's usual function) and severe (interferes significantly with participant's usual function). Treatment-emergent are events between first dose of study drug and up to end of study (2 weeks post-end of month 12) that were absent before treatment or that worsened relative to pretreatment state.	Baseline up to end of study (2 weeks post-end of month 12)
Percentage of Participants With Clinical Opiate Withdrawal Scale (COWS) Score	The presence and level of clinical opiate withdrawal signs or symptoms was determined by clinician-administered, clinical opiate withdrawal scale (COWS). It contains 11 common opiate withdrawal signs or symptoms rated by clinician (resting pulse rate, gastrointestinal upset, sweating, tremor, restlessness, yawning, pupil size, anxiety or irritability, bone or joint aches, gooseflesh skin, runny nose or tearing), rated on either 3-point, 4-point or 5-point scale, higher score indicated more symptoms of withdrawal. The total score is the sum of all items, ranging from 0 to 48, higher score indicated severe withdrawal. Participants were categorized as less than mild (score 0-4) mild (score 5-12), moderate (score 13-24), moderately severe (score 25-36) or severe (score greater than 36). Percentage of participants with mild (score 5-12), moderate (score 13-24), moderately severe (score 25-36) or severe (score greater than 36) were reported.	Baseline up to Month 12
Subjective Opiate Withdrawal Scale (SOWS) Score	The presence and level of clinical opiate withdrawal signs or symptoms was determined by participant-reported instrument, subjective opiate withdrawal scale (SOWS). It contains 16 symptoms of opiate withdrawal rated by the participant (anxiety, yawning, sweating, tearing, running nose, goose bumps, shaking, hot flashes, cold flashes, bone or muscle aches, restlessness, nauseous, vomiting, muscle twitch, stomach cramps and feel like using now). Each item is rated on a 5-point scale (0= not at all, 1= a little, 2= moderate, 3= quite a bit, 4= extreme). The total score is the sum of all items, ranging from 0 to 64, higher score indicated severe withdrawal.	Baseline, Week 1, 4, Month 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Observed Steady-state Plasma Concentrations (Cobs) of Oxycodone		Week 1, 4, Month 2, 3, 6, 9, 12 or early termination
Observed Steady-state Plasma Concentrations (Cobs) of Noroxycodone	Noroxycodone was a metabolite of Oxycodone.	Week 1, 4, Month 2, 3, 6, 9, 12 or early termination
Observed Steady-state Plasma Concentrations (Cobs) of Naltrexone		Week 1, 4, Month 2, 3, 6, 9, 12 or early termination
Observed Steady-state Plasma Concentrations (Cobs) of 6-Beta-naltrexol	6-Beta-naltrexol was a metabolite of naltrexone.	Week 1, 4, Month 2, 3, 6, 9, 12 or early termination
Time to Stabilization of Study Medication	Stabilization was considered to have occurred when: total daily dose of oxycodone and naltrexone remained unchanged for greater than or equal to (>=) 3 consecutive days, daily acetaminophen used remained at 1 gram or less and immediate-release oxycodone was not being used as a rescue medication. Days to stabilization = date of stabilization - date of first dose + 1.	Baseline up to Month 12
Duration of Exposure to Study Medication	Duration of exposure to study medication during the course of the study was assessed.	Baseline up to 2 weeks after last dose
Mean Daily Dose of Study Medication (Oxycodone Component)		Baseline- less than (<) Week 1, Week 1-<4, Week 4-<Month 2, Month 2-<3, Month 3-<4, Month 4-< 5, Month 5-<6, Month 6-<7, Month 7-<8, Month8-<9, Month 9-<10, Month 10-<11, Month 11-<12, Month 12-<End of study (2 weeks post end of Month 12)
Number of Participants With Rescue Medication (Acetaminophen Tablets)	Participants had acetaminophen up to 2 grams per day during the treatment period of the study as rescue medication.	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)
Percentage of Participants With Response to Urine Drug Test	Participants with a positive urine drug test for illicit drug substances (marijuana, cocaine, amphetamines, methamphetamines, phencyclidine, and ecstasy), or unexpected drug substances (those other than reported by the participant as therapeutic concomitant medications such as opiates and methadone), or a negative urine test for the expected opioid (oxycodone) was assessed.	Screening, Week 4, Month 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 or early termination
Percentage of Participants With Current Opioid Misuse Measure (COMM) Score of 9 or Above	The COMM is a 17-item self-report questionnaire to monitor for aberrant medication-related behaviors among chronic pain participants. Participants are asked to indicate the frequency of individual behaviors on a scale from 0 to 4 (0 = never, 1 = seldom, 2 = sometimes, 3 = often, 4= very often). The total COMM score is the sum of the 17 item scores with a range from 0 to 68. Higher score indicated a higher risk for aberrant medication- related behavior. A score of 9 or higher was defined as high risk for aberrant medication- related behavior.	Baseline, Week 4, Month 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 or early termination
Mean Daily Dose of Immediate-release Oxycodone as Rescue Medication	Immediate-release oxycodone as a single ingredient product was used as a rescue medication only during the first 4 weeks of the treatment period to support the initiation of oxycodone HCl and naltrexone HCl treatment.	Up to Week 4
Participants Global Assessment of Treatment Satisfaction	Participant global assessment of treatment satisfaction was scored on a 5-point categorical scale based on response to the question "Please rate your overall satisfaction with the study drug you received?" where 1 = very dissatisfied, 2 = dissatisfied, 3 = neither satisfied nor dissatisfied, 4 = satisfied, 5 = very satisfied.	Week 1, 4, Month 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, end of treatment
Mean Change From Baseline in Pain Right Now Score at Weeks 1, 4, Months 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 12 or Early Termination	The pain intensity scale consisted of 4 questions (pain at its worst in the last 24 hours, pain at its least in the last 24 hours, pain on the average in the last 24 hours and pain right now) each scored on an 11-point numerical rating scale, where 0 = no pain and 10 = pain as bad as you can imagine. "Pain right now" was reported.	Baseline, Week 1, 4, Months 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 12 or Early Termination (ET)
Mean Change From Baseline in Average Pain Score at Weeks 1, 4, Months 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 12 or Early Termination	The pain intensity scale consisted of 4 questions (pain at its worst in the last 24 hours, pain at its least in the last 24 hours, pain on the average in the last 24 hours and pain right now) each scored on an 11-point numerical rating scale, where 0 = no pain and 10 = pain as bad as you can imagine. Pain on average in the last 24 hours" was reported.	Baseline, Week 1, 4, Months 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 12 or Early Termination
Mean Change From Baseline in Worst Pain Score at Weeks 1, 4, Months 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 12 or Early Termination	The pain intensity scale consisted of 4 questions (pain at its worst in the last 24 hours, pain at its least in the last 24 hours, pain on the average in the last 24 hours and pain right now) each scored on an 11-point numerical rating scale, where 0 = no pain and 10 = pain as bad as you can imagine. "Pain at its worst in the last 24 hours" was reported.	Baseline, Week 1, 4, Months 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 12 or Early Termination

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

General 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.

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start: December 1, 2010
• Primary Completion (Actual): May 1, 2012
• Study Completion (Actual): May 1, 2012

Study Registration Dates

• First Submitted: September 2, 2011
• First Submitted That Met QC Criteria: September 2, 2011
• First Posted (Estimate): September 5, 2011

Study Record Updates

• Last Update Posted (Estimate): November 21, 2016
• Last Update Submitted That Met QC Criteria: September 28, 2016
• Last Verified: June 1, 2016

More Information

Terms related to this study

• Keywords: oxycodone; naltrexone; Chronic noncancer pain
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Opioid; Narcotics; Narcotic Antagonists; Alcohol Deterrents; Naltrexone; Oxycodone
• Other Study ID Numbers: ALO-02-10-3001; B4531001 (Other Identifier: Alias Study Number)