A Multicenter, 12 Week, Double-blind, Placebo-controlled, Randomized Withdrawal Study To Determine The Efficacy And Safety Of Alo-02 (Oxycodone Hydrochloride And Naltrexone Hydrochloride) Extended-release Capsules In Subjects With Moderate To Severe Chronic Low Back Pain

简要总结

主要结局

次要结局

• Change in Roland-Morris Disability Questionnaire (RMDQ) Total Score From Randomization Baseline to the End of Double-Blind Week 12 (or Final Visit).(Week 12)
• Percentage of Participants With Improvement in Weekly Average eDiary NRS-Pain Scores From Screening to Final 2 Weeks of the Double-Blind Treatment Period (Average of Weeks 11 and 12) by Cumulative Percent Reduction ≥30%(Weeks 11 and 12)
• Percentage of Participants With Improvement in Weekly Average eDiary NRS-Pain Scores From Screening to Final 2 Weeks of the Double-Blind Treatment Period (Average of Weeks 11 and 12) by Cumulative Percent Reduction ≥40%(Weeks 11 and 12)
• Percentage of Participants With Improvement in Weekly Average eDiary NRS-Pain Scores From Screening to Final 2 Weeks of the Double-Blind Treatment Period (Average of Weeks 11 and 12) by Cumulative Percent Reduction of Greater or Equal to (≥) 20%(Weeks 11 and 12)
• Percentage of Participants With Improvement in Weekly Average eDiary NRS-Pain Scores From Screening to Final 2 Weeks of the Double-Blind Treatment Period (Average of Weeks 11 and 12) by Cumulative Percent Reduction ≥50%(Weeks 11 and 12)
• Median Time to 20%, 30%, 40%, or 50% Analgesic Response From Screening Period to End of Open-Label Treatment(Screening, Week 4, 5, or 6)
• Percentage of Participants With a 20%, 30%, 40%, or 50% Analgesic Response From Screening Period to Randomization Baseline(Screening, Randomization Baseline (up to 6 weeks))
• Median Time to 20%, 30%, 40%, or 50% Analgesic Response From Screening Period to Randomization Baseline(Screening, Randomization Baseline (up to 6 weeks))
• Percentage of Participants With a 20%, 30%, 40%, or 50% Loss of Analgesic Response From Randomization Baseline During the Double-Blind Treatment Period(Randomization Baseline, up to Week 12)
• Percentage of Participants Discontinuing Treatment for Investigator-Reported Lack of Efficacy(Week 1 up to Week 12)
• SOWS Total Score During the Double-Blind Treatment Period(Randomization Baseline, Weeks 1, 2, 4, 8, and 12)
• Percentage (%) of Participants With Shift in Patient Global Assessment (PGA) by Category With Baseline PGA Score of Very Good (1), Good (2), Fair (3), Poor (4), Very Poor (5) From Randomization Baseline to End of Double-Blind Week 12 (or Final Visit).(Randomization Baseline, Week 12)
• Change From Screening Period to End of Open-Label Treatment in Brief Pain Inventory - Short Form (BPI-sf): Worst Pain, Least Pain, Average Pain, Pain Right Now, Pain Severity Index, Pain Interference Index(Screening, Week 4, 5, or 6)
• Change From Screening Period to Randomization Baseline in BPI-sf: Worst Pain, Least Pain, Average Pain, Pain Right Now, Pain Severity Index, Pain Interference Index(Screening, Randomization Baseline)
• Change From Randomization Baseline to End of Double-Blind Weeks 2, 4, 8, and 12 (or Final Visit) in BPI-sf Scores of Average Pain(Weeks 2, 4, 8, and 12)
• Change From Screening to End of Double-Blind Weeks 2, 4, 8, and 12 (or Final Visit) in BPI-sf Scores of Worst Pain(Weeks 2, 4, 8 and 12)
• Change From Screening to End of Double-Blind Weeks 2, 4, 8, and 12 (or Final Visit) in BPI-sf Scores of Least Pain(Weeks 2, 4, 8, and 12)
• Average Daily Use of Rescue Acetaminophen (Milligrams Per Day [mg/Day]) During the Double-Blind Treatment Period(Daily from Day 1 of the Double-Blind Period through Week 12)
• Change From Randomization Baseline to End of Double-Blind Weeks 2, 4, 8, and 12 (or Final Visit) in BPI-sf Scores of Worst Pain(Weeks 2, 4, 8, and 12)
• Change From Randomization Baseline to End of Double-Blind Weeks 2, 4, 8, and 12 (or Final Visit) in BPI-sf Scores of Least Pain(Weeks 2, 4, 8, and 12)
• Change From Randomization Baseline to End of Double-Blind Weeks 2, 4, 8, and 12 (or Final Visit) in BPI-sf Scores of Pain Right Now(Weeks 2, 4, 8, and 12)
• Change From Randomization Baseline to End of Double-Blind Weeks 2, 4, 8, and 12 (or Final Visit) in BPI-sf Scores of Pain Severity Index(Weeks 2, 4, 8, and 12)
• Change From Screening to End of Double-Blind Weeks 2, 4, 8, and 12 (or Final Visit) in BPI-sf Scores of Average Pain(Weeks 2, 4, 8, and 12)
• Change From Screening to End of Double-Blind Weeks 2, 4, 8, and 12 (or Final Visit) in BPI-sf Scores of Pain Right Now(Weeks 2, 4, 8, and 12)
• Change From Screening to End of Double-Blind Weeks 2, 4, 8, and 12 (or Final Visit) in BPI-sf Scores of Pain Severity Index(Weeks 2, 4, 8, and 12)
• Area Under the Curve (AUC) of eDiary NRS-Pain Scores From Randomization Baseline to Final 2 Weeks of the Double-Blind Treatment Period (Weeks 11 and 12)(Randomization Baseline, Weeks 11 and 12)
• Change From Randomization Baseline to End of Double-Blind Weeks 2, 4, 8, and 12 (or Final Visit) in BPI-sf Scores of Pain Interference Index(Weeks 2, 4, 8, and 12)
• Change From Screening to End of Double-Blind Weeks 2, 4, 8, and 12 (or Final Visit) in BPI-sf Scores of Pain Interference Index(Weeks 2, 4, 8, and 12)
• Percentage of Participants With a 20%, 30%, 40%, or 50% Analgesic Response From Screening Period to End of Open-Label Treatment(Screening, Week 4, 5 or 6)
• Percentage of Participants With Opiate Withdrawal During the Open-Label Titration Period by COWS Category(Screening, Weeks 1, 2, 3, 4, 5, 6 (or Early Termination))
• Median Time to 20%, 30%, 40%, or 50% Loss of Analgesic Response From Baseline During the Double-Blind Treatment Period(Randomization Baseline, up to Week 12)
• Median Time to Treatment Discontinuation for Investigator-Reported Lack of Efficacy During the Double-Blind Treatment Period(Week 1 up to Week 12)
• Clinical Opiate Withdrawal Scale (COWS) Total Score During the Open-Label Titration Period(Screening, Weeks 1, 2, 3, 4, 5, and 6)
• COWS Total Score During the Double-Blind Treatment Period(Randomization Baseline, Weeks 1, 2, 4, 8, and 12)
• COWS Total Score During the Post-Treatment Period(Follow-Up (FU) Weeks 1 and 2)
• Percentage of Participants With Opiate Withdrawal During the Double-Blind Treatment Period by COWS Category(Randomization Baseline, Weeks 1, 2, 4, 8, 12 (or Early Termination))
• Percentage of Participants With Opiate Withdrawal During Post-Treatment by COWS Category(Follow-Up Weeks 1 and 2)
• SOWS Total Score During the Post-Treatment Period(Follow-Up Weeks 1 and 2)
• Subjective Opiate Withdrawal Scale (SOWS) During the Open-Label Titration Period(Screening, Weeks 1, 2, 3, 4, 5, and 6)
• Change From Screening Period to End of Open-Label Titration Period in Roland-Morris Disability Questionnaire (RMDQ) Total Score for All Participants(Screening, Week 6 (or Early Termination))
• Percentage of Participants With Shift From Screening to the End of the Open-Label Titration Period in PGA of Low Back Pain by Category in Participants With Screening PGA Score of Very Good, Good, Fair, Poor, Very Poor(Screening, Randomization Baseline, or Early Termination)
• Change From Randomization Baseline to the End of Double-Blind Weeks 2, 4, and 8 in RMDQ Total Score(Randomization Baseline, Weeks 2, 4, and 8)
• Percentage of Participants With Shift From Randomization Baseline to End of Double-Blind Week 4 in PGA of Low Back Pain by Category in Participants With Randomization Baseline PGA Score of Very Good, Good, Fair, Poor, Very Poor(Randomization Baseline, Week 4)
• Satisfaction With Treatment at the End of Open-Label Titration Period for All Participants(End of Open-Label Titration Period (Week 4, 5, or 6 or Early Termination))
• Change From Screening Period to End of Double-Blind Week 12 (or Final Visit) in SF-36v2 Health Survey(Screening, Week 12)
• Change From Screening Period to the End of Open-Label Titration Period in Participant Assessment of Overall Health State Using the EQ-5D VAS(Screening, Week 6 (or Early Termination))
• Change From Screening Period to Randomization Baseline in Participant Assessment of Overall Health State Using the EQ-5D VAS(Screening, Randomization Baseline)
• Change From Randomization Baseline to End of Double-Blind Week 12 (or Final Visit) in Participant Assessment of Overall Health State Using the EQ-5D VAS(Randomization Baseline, Week 12)
• Change From Randomization Baseline to End of Double-Blind Weeks 4, 8, and 12 (or Final Visit) in WPAI:SHP Percent Impairment Due to Low Back Pain(Randomization Baseline, Weeks 4, 8, and 12)
• Change From Screening to End of Open-Label Titration Period in HRU Questionnaire: Money Spent on Physical Treatments in Past 4 Weeks(Screening, Week 6 (or Early Termination))
• Change From Screening Period to Randomization Baseline in RMDQ Total Score(Screening, Randomization Baseline)
• Change From Screening Period to End of Double-Blind Weeks 2, 4, 8, and 12 (or Final Visit) in RMDQ Total Score(Screening, Weeks 2, 4, 8, and 12)
• Percentage of Participants With Shift From Screening to Randomization Baseline in PGA of Low Back Pain by Category in Participants With Screening PGA Score of Very Good, Good, Fair, Poor, Very Poor(Screening, Randomization Baseline)
• Percentage of Participants With Shift From Randomization Baseline to End of Double-Blind Week 8 in PGA of Low Back Pain by Category in Participants With Randomization Baseline PGA Score of Very Good , Good, Fair, Poor, Very Poor(Randomization Baseline, Week 8)
• Satisfaction With Treatment at Randomization Baseline(Randomization Baseline)
• Percentage of Participants Who Reported Being Satisfied/Very Satisfied With Treatment on the Satisfaction With Treatment Questionnaire During the Double-Blind Treatment Period(Week 12 or Early Termination)
• Change From Screening Period to the End of Open-Label Titration Period in Short Form-36v2 (SF-36v2) Health Survey Score(Screening, Week 6 (or Early Termination))
• Change From Screening Period to Randomization Baseline in SF-36v2 Health Survey Score(Screening, Randomization Baseline)
• Change From Screening Period to the End of Open-Label Titration Period in Participant Assessment of Overall Health State Using the EuroQol 5-Dimensions (EQ-5D) Summary Index(Screening, Week 6 (or Early Termination))
• Change From Screening Period to Randomization Baseline in Participant Assessment of Overall Health State Using the EQ-5D Summary Index(Screening, Randomization Baseline)
• Change From Screening Period to End of Open-Label in Work Productivity and Activity Impairment Questionnaire: Specific Health Problem (WPAI:SHP): % Work Time Missed, % Impairment, % Overall Work Impairment, % Activity Impairment Due to Low Back Pain(Screening, Week 6 (or Early Termination))
• Change From Screening Period to End of Double-Blind Weeks 4, 8, and 12 (or Final Visit) in WPAI:SHP Percent Impairment Due to Low Back Pain(Screening, Weeks 4, 8, and 12)
• Change From Randomization Baseline to End of Double-Blind Weeks 4, 8 and 12 (or Final Visit) in HRU Questionnaire: Money Spent on Treatments(Randomization Baseline, Weeks 4, 8, and 12)
• Change From Randomization Baseline to End of Double-Blind Weeks 4, 8 and 12 (or Final Visit) in HRU Questionnaire: Nights Spent in Hospital(Randomization Baseline, Weeks 4, 8, and 12)
• Percentage of Participants With Shift From Screening Period to the End of Double-Blind Weeks 4, 8 and 12 (or Final Visit) in Hospitalization Because of Low Back Pain as Assessed Using the HRU Questionnaire(Screening, Weeks 4, 8, and 12)
• Mean Oxycodone Duration of Treatment During the Double-Blind Treatment Period(Double-Blind Period)
• Change From Randomization Baseline to the End of Double-Blind Week 12 (or Final Visit) in SF-36v2 Health Survey(Randomization Baseline, Week 12)
• Change From Screening Period to End of Double-Blind Week 12 (or Final Visit) in Participant Assessment of Overall Health State Using EQ-5D Summary Index(Screening, Week 12)
• Change From Screening Period to End of Double-Blind Week 12 (or Final Visit) in Participant Assessment of Overall Health State Using EQ-5D VAS(Screening, Week 12)
• Change From Screening Period to Randomization Baseline in WPAI:SHP: Percent Work Time Missed, Percent Impairment, Percent Overall Work Impairment, Percent Activity Impairment Due to Low Back Pain(Screening, Randomization Baseline)
• Change From Randomization Baseline to End of Double-Blind Weeks 4, 8, and 12 (or Final Visit) in WPAI:SHP Percent Work Time Missed Due to Low Back Pain(Randomization Baseline, Weeks 4, 8, and 12)
• Change From Randomization Baseline to End of Double-Blind Weeks 4, 8, and 12 (or Final Visit) in WPAI:SHP Percent Activity Impairment Due to Low Back Pain(Randomization Baseline, Weeks 4, 8, and 12)
• Change From Screening Period to End of Double-Blind Weeks 4, 8, and 12 (or Final Visit) in WPAI:SHP Percent Work Time Missed Due to Low Back Pain(Screening, Weeks 4, 8, and 12)
• Percentage of Participants With Shift From Screening Period to End of Open-Label Titration Period in Hospitalization Because of Low Back Pain as Assessed Using the Healthcare Resource Use (HRU) Questionnaire(Screening, Week 6 (or Early Termination))
• Change From Randomization Baseline to End of Double-Blind Week 12 (or Final Visit) in Participant Assessment of Overall Health State Using EQ-5D Summary Index(Randomization Baseline, Week 12)
• Change From Randomization Baseline to End of Double-Blind Weeks 4, 8, and 12 (or Final Visit) in WPAI:SHP Percent Overall Work Impairment Due to Low Back Pain(Randomization Baseline, Weeks 4, 8, and 12)
• Change From Screening Period to End of Double-Blind Weeks 4, 8, and 12 (or Final Visit) in WPAI:SHP Percent Overall Work Impairment Due to Low Back Pain(Screening, Weeks 4, 8, and 12)
• Change From Screening Period to End of Double-Blind Weeks 4, 8, and 12 (or Final Visit) in WPAI:SHP Percent Activity Impairment Due to Low Back Pain(Screening, Weeks 4, 8, and 12)
• Change From Randomization Baseline to End of Double-Blind Weeks 4, 8 and 12 (or Final Visit) in HRU Questionnaire: Number of Office Visits Related to or Medications Used for Chronic Low Back Pain(Randomization Baseline, Weeks 4, 8, and 12)
• Percentage of Participants With Shift From Screening Period to Randomization Baseline in Hospitalization Because of Low Back Pain as Assessed Using the HRU Questionnaire(Screening, Randomization Baseline)
• Change From Screening to Randomization Baseline in HRU Questionnaire: Number of Office Visits Directly Related or Any Medication Used for Chronic Low Back Pain(Screening, Randomization Baseline)
• Change From Screening to End of Open-Label Titration Period in HRU Questionnaire: Nights Stayed in Hospital(Screening, Week 6 (or Early Termination))
• Change From Screening to Randomization Baseline in HRU Questionnaire: Money Spent on Physical Treatments in Past 4 Weeks(Screening, Randomization Baseline)
• Change From Screening to Randomization Baseline in HRU Questionnaire: Nights Stayed in Hospital(Screening, Randomization Baseline)
• Change From Screening to End of Open-Label Titration Period in HRU Questionnaire: Number of Office Visits Directly Related or Any Medication Used for Chronic Low Back Pain(Screening, Week 6 (or Early Termination))
• Percentage of Participants With Shift From Randomization Baseline to End of Double-Blind Weeks 4, 8, and 12 (or Final Visit) in Hospitalization Because of Low Back Pain as Assessed Using the HRU Questionnaire(Randomization Baseline, Weeks 4, 8, and 12 (or Early Termination))
• Change From Screening Period to End of Double-Blind Weeks 4, 8 and 12 (or Final Visit) in HRU Questionnaire: Money Spent on Treatment for Chronic Low Back Pain(Screening, Weeks 4, 8, and 12)
• Change From Screening Period to End of Double-Blind Weeks 4, 8 and 12 (or Final Visit) in HRU Questionnaire: Nights in Hospital for Chronic Low Back Pain(Screening, Weeks 4, 8, and 12)
• Median Oxycodone Duration of Titration During the Open-Label Titration Period(Open-Label Period)
• Naltrexone and 6-β-naltrexol Observed Steady-State Plasma Concentration During the Double Blind Treatment Period(Blood samples were taken within +/-4 hours of the morning dose of study drug at Randomization Baseline, Weeks 4, 8, and 12)
• Change From Screening Period to End of Double-Blind Weeks 4, 8 and 12 (or Final Visit) in HRU Questionnaire: Number of Office Visits Related or Medication Used for Chronic Low Back Pain(Screening, Weeks 4, 8, and 12)
• Mean Oxycodone Average Daily Dose During the Open-Label Titration Period(Open-Label Period)
• Mean Oxycodone Duration of Titration During the Open-Label Titration Period(Open-Label Period)
• Median Oxycodone Average Daily Dose During the Open-Label Titration Period(Open-Label Period)
• Mean Oxycodone Average Daily Dose During the Double-Blind Treatment Period(Double-Blind Period)
• Median Oxycodone Average Daily Dose During the Double-Blind Treatment Period(Double-Blind Period)
• Naltrexone and 6-β-naltrexol Observed Steady-State Plasma Concentration During the Titration Period(Blood samples were taken within +/-4 hours of the morning dose of ALO-02 at Week 6/Early Termination, Randomization Baseline)
• Median Oxycodone Duration of Treatment During the Double-Blind Treatment Period(Double-Blind Period)
• Oxycodone and Noroxycodone Observed Steady-State Plasma Concentration During the Titration Period(Blood samples were taken within +/-4 hours of the morning dose of ALO-02 at Week 6/Early Termination, Randomization Baseline)
• Oxycodone and Noroxycodone Observed Steady-State Plasma Concentration During the Double-Blind Treatment Period(Blood samples were taken within +/-4 hours of the morning dose of study drug at Randomization Baseline, Weeks 4, 8, and 12)