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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT01428583
First received: September 2, 2011
Last updated: September 28, 2016
Last verified: June 2016
  Purpose
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.

Condition Intervention Phase
Chronic Noncancer Pain
Drug: oxycodone HCl and naltrexone HCl extended-release capsules
Phase 3

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Masking: Open Label
Primary Purpose: Supportive Care
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

Resource links provided by NLM:


Further study details as provided by Pfizer:

Primary Outcome Measures:
  • 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) ] [ Designated as safety issue: Yes ]
    An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An AE that was attributed to study drug in a participant who received study drug was defined as an adverse reaction. Treatment-emergent are events between first dose of study drug and up to end of study (2 weeks post-end of month 12) that were absent before treatment or that worsened relative to pretreatment state.


Secondary Outcome Measures:
  • 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) ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: Yes ]
    The presence and level of clinical opiate withdrawal signs or symptoms was determined by participant-reported instrument, subjective opiate withdrawal scale (SOWS). It contains 16 symptoms of opiate withdrawal rated by the participant (anxiety, yawning, sweating, tearing, running nose, goose bumps, shaking, hot flashes, cold flashes, bone or muscle aches, restlessness, nauseous, vomiting, muscle twitch, stomach cramps and feel like using now). Each item is rated on a 5-point scale (0= not at all, 1= a little, 2= moderate, 3= quite a bit, 4= extreme). The total score is the sum of all items, ranging from 0 to 64, higher score indicated severe withdrawal.


Other Outcome Measures:
  • Observed Steady-state Plasma Concentrations (Cobs) of Oxycodone [ Time Frame: Week 1, 4, Month 2, 3, 6, 9, 12 or early termination ] [ Designated as safety issue: No ]
  • Observed Steady-state Plasma Concentrations (Cobs) of Noroxycodone [ Time Frame: Week 1, 4, Month 2, 3, 6, 9, 12 or early termination ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
  • Observed Steady-state Plasma Concentrations (Cobs) of 6-Beta-naltrexol [ Time Frame: Week 1, 4, Month 2, 3, 6, 9, 12 or early termination ] [ Designated as safety issue: No ]
    6-Beta-naltrexol was a metabolite of naltrexone.

  • Time to Stabilization of Study Medication [ Time Frame: Baseline up to Month 12 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]
  • 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) ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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.


Enrollment: 395
Study Start Date: December 2010
Study Completion Date: May 2012
Primary Completion Date: May 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: ALO-02

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01428583

  Show 32 Study Locations
Sponsors and Collaborators
Pfizer
Investigators
Study Director: Pfizer CT.gov Call Center Pfizer
  More Information

Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT01428583     History of Changes
Other Study ID Numbers: ALO-02-10-3001  B4531001 
Study First Received: September 2, 2011
Results First Received: September 28, 2016
Last Updated: September 28, 2016
Health Authority: United States: Food and Drug Administration

Keywords provided by Pfizer:
Chronic noncancer pain
oxycodone
naltrexone

Additional relevant MeSH terms:
Naltrexone
Oxycodone
Narcotic Antagonists
Physiological Effects of Drugs
Sensory System Agents
Peripheral Nervous System Agents
Analgesics, Opioid
Narcotics
Central Nervous System Depressants
Analgesics

ClinicalTrials.gov processed this record on December 08, 2016