A Research Study of an Investigational Drug ALO-02 (Oxycodone Hydrochloride and Naltrexone Hydrochloride) in Patients With Moderate to Severe Chronic Low Back Pain

Study Overview
=================
Brief Summary
-----------------
The primary objective of the study is to determine the analgesic efficacy and safety of ALO-02 extended-release capsules, when compared to placebo, in subjects with moderate to severe chronic low back pain.

Official Title
-----------------
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

Conditions
-----------------
Chronic Pain, Low Back Pain, Analgesia

Intervention / Treatment
-----------------
* Drug: ALO-02
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Moderate-to-severe chronic low back pain present for at least 3 months. Require a continuous around-the-clock opioid analgesic for an extended period of time. Refrain from taking other opioid and non-opioid medications during the study. Exclusion Criteria: Active or within a past 2 years a history of lumbosacral radiculopathy or chronic low back pain due to other underlying disorders such as spinal stenosis with neurologic impairment, cancer, infection, or post-surgical intervention. Documented diagnosis of ongoing pain due to other chronic pain conditions which may interfere with assessment of chronic low back pain. Active or ongoing or history of alcohol or drug abuse.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ALO-02<br> | Drug: ALO-02<br>* 20 to 160mg total daily dose of oxycodone, divided into symmetric doses and administered twice daily<br>* Other names: oxycodone HCl and naltrexone HCl;|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* oral placebo, divided into symmetric doses and administered twice daily<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Weekly Average Electronic Diary (eDiary) Numeric Rating Scale -Pain (NRS-Pain) Score From Randomization Baseline to Final 2 Weeks (Average of Weeks 11 and 12) | Weekly average diary NRS-Pain scores were derived from the daily NRS-pain scale and calculated as the mean of the last 7 days. NRS-Pain scores based on an 11-point numerical rating scale from 0 (no pain) to 10 (worst possible pain). Higher scores indicate greater pain. | Weeks 11 and 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Roland-Morris Disability Questionnaire (RMDQ) Total Score From Randomization Baseline to the End of Double-Blind Week 12 (or Final Visit). | The RMDQ is a 24-item questionnaire designed to measure self-rated disability due to back pain. An individual participant's score can vary from 0 (no disability) to 24 (severe disability), with a lower score indicating better function; higher score indicating greater disability. | Week 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). | Measure represents the score at Randomization Baseline / score at Week 12 (or Early Termination) in PGA, a global evaluation that utilizes a 5-point Likert scale with a score of 1 being the best (Very Good) and a score of 5 being the worst (Very Poor). | Randomization Baseline, 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 of Greater or Equal to (≥) 20% | Weekly average Diary NRS-pain scores are derived from the daily pain NRS and calculated as the mean of the last 7 days. Scores range from 0 equals (=) no pain to 10 = worst possible pain. Higher scores indicate greater pain. | 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 ≥30% | Weekly average Diary NRS-pain scores are derived from the daily pain NRS and calculated as the mean of the last 7 days. Scores range from 0 = no pain to 10 = worst possible pain. Higher scores indicate greater pain. | 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% | Weekly average Diary NRS-pain scores are derived from the daily pain NRS and calculated as the mean of the last 7 days. Scores range from 0 = no pain to 10 = worst possible pain. Higher scores indicate greater pain. | 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% | Weekly average Diary NRS-pain scores are derived from the daily pain NRS and calculated as the mean of the last 7 days. Scores range from 0 = no pain to 10 = worst possible pain. Higher scores indicate greater pain. | Weeks 11 and 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 | BPI-sf is an 11-item self-report questionnaire that is designed to assess the severity and impact of pain on daily functions. BPI-sf includes 4 questions that assess pain intensity (worst, least, average, right now) and 7 questions that assess impact of pain on daily functions (general activity, mood, walking ability, normal work, relations with other people, sleep, enjoyment of life). BPI-sf scores range from 0=No pain to 10=Pain as bad as you can imagine; Higher scores indicate greater pain. Pain Severity Index is the mean of the 4 pain scores (worst, least, average, and right now) on the BPI-sf; range is 0=No pain to 10=Pain as bad as you can imagine; A higher score indicates greater pain severity. Pain Interference Index is the mean of the scores for the 7 items of the BPI-sf; range is 0=Does not interfere to 10=Completely interferes. | 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 | BPI-sf scores range from 0=No pain to 10=Pain as bad as you can imagine; Higher scores indicate greater pain. Pain Severity Index is the mean of the 4 pain scores (worst, least, average, and right now) on the BPI-sf; range is 0=No pain to 10=Pain as bad as you can imagine; A higher score indicates greater pain severity. Pain Interference Index is the mean of the scores for the 7 items of the BPI-sf; range is 0=Does not interfere to 10=Completely interferes. | 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 Worst Pain | BPI-sf scores range from 0=No pain to 10=Pain as bad as you can imagine; Higher scores indicate greater 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 | BPI-sf scores range from 0=No pain to 10=Pain as bad as you can imagine; Higher scores indicate greater 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 Average Pain | BPI-sf scores range from 0=No pain to 10=Pain as bad as you can imagine; Higher scores indicate greater 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 | BPI-sf scores range from 0=No pain to 10=Pain as bad as you can imagine; Higher scores indicate greater 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 Severity Index | Pain Severity Index is the mean of the 4 pain scores (worst, least, average, and right now) on the BPI-sf; range is 0=No pain to 10=Pain as bad as you can imagine; a higher score indicates greater pain severity. | 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 Interference Index | Pain Interference Index is the mean of the scores for the 7 items of the BPI-sf; range is 0=Does not interfere to 10=Completely interferes. | 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 | BPI-sf scores range from 0=No pain to 10=Pain as bad as you can imagine; Higher scores indicate greater 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 | BPI-sf scores range from 0=No pain to 10=Pain as bad as you can imagine; Higher scores indicate greater 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 Average Pain | BPI-sf scores range from 0=No pain to 10=Pain as bad as you can imagine; higher scores indicate greater 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 | BPI-sf scores range from 0=No pain to 10=Pain as bad as you can imagine; higher scores indicate greater 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 Severity Index | Pain Severity Index is the mean of the 4 pain scores (worst, least, average, and right now) on the BPI-sf; range is 0=No pain to 10=Pain as bad as you can imagine; a higher score indicates greater pain severity. | 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 | Pain Interference Index is the mean of the scores for the 7 items of the BPI-sf; range is 0=Does not interfere to 10=Completely interferes. | 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) | NRS-Pain scores based on an 11-point numerical rating scale from 0 (no pain) to 10 (worst possible pain). AUC was calculated using daily change from Baseline scores from Baseline until the last dose date in the Double-Blind Treatment Period. AUC was calculated for each participant using the linear trapezoidal method. Higher scores indicate greater pain. | Randomization Baseline, Weeks 11 and 12 | 
| Average Daily Use of Rescue Acetaminophen (Milligrams Per Day [mg/Day]) During the Double-Blind Treatment Period | The amount of acetaminophen administered for each treatment during the Double-Blind Treatment Period. Average daily use calculated as: total dose of rescue medication during Double-Blind Period divided by the number of days in Double-Blind Period. | Daily from Day 1 of the Double-Blind Period through Week 12 | 
| Percentage of Participants With a 20%, 30%, 40%, or 50% Analgesic Response From Screening Period to End of Open-Label Treatment | The percentage of analgesic response is defined as: (rolling 7-day mean pain score during Titration Period - Screening Period pain intensity score) divided by Screening Period pain intensity score times100. | Screening, Week 4, 5 or 6 | 
| Median Time to 20%, 30%, 40%, or 50% Analgesic Response From Screening Period to End of Open-Label Treatment | The percentage of analgesic response is defined as: (rolling 7-day mean pain score during Titration Period minus (-) Screening Period pain intensity score) divided by Screening Period pain intensity score times 100. An event was defined as a participant with 20, 30, 40, or 50% analgesic response from Screening. If there was no event for a participant, time to the event was considered censored at Day 42 of the Titration Period or before Day 42 of the Titration Period at the time of the last diary pain score. The survival duration begins on the date of first dose of study drug in the Titration Period and is calculated as the [date of event or last diary pain score - date of first dose in Titration Period +1]. | Screening, Week 4, 5, or 6 | 
| Percentage of Participants With a 20%, 30%, 40%, or 50% Analgesic Response From Screening Period to Randomization Baseline | The percentage of analgesic response is defined as: (rolling 7-day mean pain score during Titration Period - Screening Period pain intensity score) divided by Screening Period pain intensity score times 100. | Screening, Randomization Baseline (up to 6 weeks) | 
| Median Time to 20%, 30%, 40%, or 50% Analgesic Response From Screening Period to Randomization Baseline | The percentage of analgesic response is defined as: (rolling 7-day mean pain score during Titration Period - Screening Period pain intensity score) divided by Screening Period pain intensity score times 100. If there was no event for a participant, time to the event was considered censored at Day 42 of the Titration Period or before Day 42 of the Titration Period at the time of the last diary pain score. The survival duration begins on the date of first dose of study drug in the Titration Period and is calculated as the [date of event or last diary pain score - date of first dose in Titration Period +1]. | 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 | The percentage of lost analgesic response is defined as: (rolling 7-day mean pain score during Double-Blind Period - Randomization Baseline pain intensity score) divided by Randomization Baseline pain intensity score times 100. If there was no event for a participant, time to the event was considered censored at Day 84 or before Day 84 at the time of the last diary pain score. The survival duration began on the date of first dose of study drug in the Double-Blind Period and was calculated as the [date of event or last diary pain score - date of first dose in Double-Blind Treatment +1]. | Randomization Baseline, up to Week 12 | 
| Median Time to 20%, 30%, 40%, or 50% Loss of Analgesic Response From Baseline During the Double-Blind Treatment Period | The percentage of lost analgesic response was defined as: (rolling seven day mean pain score during Double-Blind Period - Randomization Baseline pain intensity score) divided by Randomization Baseline pain intensity score times 100. If there was no event for a participant, time to the event was considered censored at Day 84 or before Day 84 at the time of the last diary pain score. The survival duration began on the date of first dose of study drug in the Double-Blind Period and was calculated as the [date of event or last diary pain score - date of first dose in Double-Blind Treatment +1]. | Randomization Baseline, up to Week 12 | 
| Percentage of Participants Discontinuing Treatment for Investigator-Reported Lack of Efficacy | If there was no event for a participant, time to the event was considered censored at Day 84 or before Day 84 at time of treatment discontinuation for another reason. | Week 1 up to Week 12 | 
| Median Time to Treatment Discontinuation for Investigator-Reported Lack of Efficacy During the Double-Blind Treatment Period | If there was no event for a participant, time to the event was considered censored at Day 84 or before Day 84 at time of treatment discontinuation for another reason. The survival duration begins on the date of first dose in the Double-Blind period and is calculated as the [date of event or discontinuation - date of first dose in Double-Blind Period +1]. | Week 1 up to Week 12 | 
| Clinical Opiate Withdrawal Scale (COWS) Total Score During the Open-Label Titration Period | The COWS contains 11 common opiate withdrawal signs or symptoms rated by the investigator or designee who, for each item, checked the number that best described the participant's signs or symptoms. The minimum total COWS score is 0, the maximum is 48. Higher scores indicate a worse outcome. The summed score of the 11 items was used to assess a participant's level of opiate withdrawal. | Screening, Weeks 1, 2, 3, 4, 5, and 6 | 
| COWS Total Score During the Double-Blind Treatment Period | The COWS contains 11 common opiate withdrawal signs or symptoms rated by the investigator or designee who, for each item, checked the number that best described the participant's signs or symptoms. The minimum total COWS score is 0, the maximum is 48. Higher scores indicate a worse outcome. The summed score of the 11 items was used to assess a participant's level of opiate withdrawal. | Randomization Baseline, Weeks 1, 2, 4, 8, and 12 | 
| COWS Total Score During the Post-Treatment Period | The COWS contains 11 common opiate withdrawal signs or symptoms rated by the investigator or designee who, for each item, checked the number that best described the participant's signs or symptoms. The minimum total COWS score is 0, the maximum is 48. Higher scores indicate a worse outcome. The summed score of the 11 items was used to assess a participant's level of opiate withdrawal. | Follow-Up (FU) Weeks 1 and 2 | 
| Percentage of Participants With Opiate Withdrawal During the Open-Label Titration Period by COWS Category | The COWS contains 11 common opiate withdrawal signs or symptoms rated by the investigator or designee who, for each item, checked the number that best described the participant's signs or symptoms. The minimum total COWS score is 0, the maximum is 48. The summed score of the 11 items was used to assess a participant's level of opiate withdrawal. The scores are assessed as follows: 5-12 = mild; 13-24 = moderate; 25-36 = moderately severe; more than 36 = severe withdrawal. | Screening, Weeks 1, 2, 3, 4, 5, 6 (or Early Termination) | 
| Percentage of Participants With Opiate Withdrawal During the Double-Blind Treatment Period by COWS Category | The COWS contains 11 common opiate withdrawal signs or symptoms rated by the investigator or designee who, for each item, checked the number that best described the participant's signs or symptoms. The minimum total COWS score is 0, the maximum is 48. The summed score of the 11 items was used to assess a participant's level of opiate withdrawal. The scores are assessed as follows: 5-12 = mild; 13-24 = moderate; 25-36 = moderately severe; more than 36 = severe withdrawal. | Randomization Baseline, Weeks 1, 2, 4, 8, 12 (or Early Termination) | 
| Percentage of Participants With Opiate Withdrawal During Post-Treatment by COWS Category | The COWS contains 11 common opiate withdrawal signs or symptoms rated by the investigator or designee who, for each item, checked the number that best described the participant's signs or symptoms. The minimum total COWS score is 0, the maximum is 48. The summed score of the 11 items was used to assess a participant's level of opiate withdrawal. The scores are assessed as follows: 5-12 = mild; 13-24 = moderate; 25-36 = moderately severe; more than 36 = severe withdrawal. | Follow-Up Weeks 1 and 2 | 
| Subjective Opiate Withdrawal Scale (SOWS) During the Open-Label Titration Period | The SOWS was completed daily by the participant during any of the 2-week tapers from study drug, as well as at each study visit, using an eDiary device, and contains 16 symptoms of opiate withdrawal rated by the participant (Scale of 0 to 4: 0 = not at all, 1 = a little, 2= moderately, 3= quite a bit, 4 = extremely). The sum of the scores on each item was the total SOWS score; the minimum possible SOWS score was 0, the maximum 64. Higher scores indicate a worse outcome. | Screening, Weeks 1, 2, 3, 4, 5, and 6 | 
| SOWS Total Score During the Double-Blind Treatment Period | The SOWS was completed daily by the participant during any of the 2-week tapers from study drug, as well as at each study visit, using an eDiary device, and contains 16 symptoms of opiate withdrawal rated by the participant (Scale of 0 to 4: 0 = not at all, 1 = a little, 2= moderately, 3= quite a bit, 4 = extremely). The sum of the scores on each item was the total SOWS score; the minimum possible SOWS score was 0, the maximum 64. Higher scores indicate a worse outcome. | Randomization Baseline, Weeks 1, 2, 4, 8, and 12 | 
| SOWS Total Score During the Post-Treatment Period | The SOWS was completed daily by the participant during any of the 2-week tapers from study drug, as well as at each study visit, using an eDiary device, and contains 16 symptoms of opiate withdrawal rated by the participant (Scale of 0 to 4: 0 = not at all, 1 = a little, 2= moderately, 3= quite a bit, 4 = extremely). The sum of the scores on each item was the total SOWS score; the minimum possible SOWS score was 0, the maximum 64. Higher scores indicate a worse outcome. | Follow-Up Weeks 1 and 2 | 
| Change From Screening Period to End of Open-Label Titration Period in Roland-Morris Disability Questionnaire (RMDQ) Total Score for All Participants | RMDQ is a 24-item questionnaire designed to measure self-rated disability due to back pain the same day the questionnaire is completed. An individual participant's score could have ranged from 0 (no disability) to 24 (severe disability), with a lower score indicating better function; higher scores indicating greater disability. | Screening, Week 6 (or Early Termination) | 
| Change From Screening Period to Randomization Baseline in RMDQ Total Score | RMDQ is a 24-item questionnaire designed to measure self-rated disability due to back pain the same day the questionnaire is completed. An individual participant's score could have ranged from 0 (no disability) to 24 (severe disability), with a lower score indicating better function. | 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 | RMDQ is a 24-item questionnaire designed to measure self-rated disability due to back pain the same day the questionnaire is completed. An individual participant's score could have ranged from 0 (no disability) to 24 (severe disability), with a lower score indicating better function. | Screening, Weeks 2, 4, 8, and 12 | 
| Change From Randomization Baseline to the End of Double-Blind Weeks 2, 4, and 8 in RMDQ Total Score | RMDQ is a 24-item questionnaire designed to measure self-rated disability due to back pain the same day the questionnaire is completed. An individual participant's score could have ranged from 0 (no disability) to 24 (severe disability), with a lower score indicating better function. | Randomization Baseline, Weeks 2, 4, and 8 | 
| 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 | Represents the score at Screening / score at Randomization Baseline in PGA of low back pain, a global evaluation that utilizes a 5-point Likert scale with a score of: 1 = very good, asymptomatic and no limitation of normal activities; 2 = good, mild symptoms, and no limitation of normal activities; 3 = fair, moderate symptoms and limitation to some normal activities; 4 = poor, severe symptoms and inability to carry out most normal activities; and a score of 5 = very poor; very severe symptoms, which were intolerable and inability to carry out all normal activities. | Screening, Randomization Baseline | 
| 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 | Represents the score at Screening / score at to end of the titration period in PGA of low back pain, a global evaluation that utilizes a 5-point Likert scale with a score of: 1 = very good, asymptomatic and no limitation of normal activities; 2 = good, mild symptoms, and no limitation of normal activities; 3 = fair, moderate symptoms and limitation to some normal activities; 4 = poor, severe symptoms and inability to carry out most normal activities; and a score of 5 = very poor; very severe symptoms, which were intolerable and inability to carry out all normal activities. | Screening, Randomization Baseline, or Early Termination | 
| 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 | Represents the score at Randomization Baseline / score at Week 4 in PGA of low back pain, a global evaluation that utilizes a 5-point Likert scale with a score of: 1 = very good, asymptomatic and no limitation of normal activities; 2 = good, mild symptoms, and no limitation of normal activities; 3 = fair, moderate symptoms and limitation to some normal activities; 4 = poor, severe symptoms and inability to carry out most normal activities; and a score of 5 = very poor; very severe symptoms, which were intolerable and inability to carry out all normal activities. | Randomization Baseline, Week 4 | 
| 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 | Represents the score at Randomization Baseline / score at Week 8 in PGA of low back pain, a global evaluation that utilizes a 5-point Likert scale with a score of: 1 = very good, asymptomatic and no limitation of normal activities; 2 = good, mild symptoms, and no limitation of normal activities; 3 = fair, moderate symptoms and limitation to some normal activities; 4 = poor, severe symptoms and inability to carry out most normal activities; and a score of 5 = very poor; very severe symptoms, which were intolerable and inability to carry out all normal activities. | Randomization Baseline, Week 8 | 
| Satisfaction With Treatment at the End of Open-Label Titration Period for All Participants | Satisfaction with treatment is a single-item self-rated instrument that measures the participant's overall satisfaction with the study drug during study participation on a 5-point likert scale ranging from 1 = Very dissatisfied to 5 = Very satisfied. | End of Open-Label Titration Period (Week 4, 5, or 6 or Early Termination) | 
| Satisfaction With Treatment at Randomization Baseline | Satisfaction with treatment is a single-item self-rated instrument that measures the participant's overall satisfaction with the study drug during study participation on a 5-point likert scale ranging from 1 = Very dissatisfied to 5 = Very satisfied. | 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 | Participants used an electronic tablet at the center to rate their overall treatment satisfaction with study drug during study participation using a 5-point categorical scale (1 = very dissatisfied, 2 = dissatisfied, 3 = neither satisfied nor dissatisfied, 4 = satisfied, 5 = very satisfied). | 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 | SF-36v2 Health Survey is a self-administered questionnaire consisting of 36 questions, measuring 8 health aspects; physical functioning, role limitations due to physical problems, social functioning, bodily pain, mental health, role limitations due to emotional problems, vitality, and general health perception. These domains also combine to form two component summary scores evaluating mental health and physical health. The minimum score is 0 and the maximum score is 100. A higher scores indicates a better health state. | Screening, Week 6 (or Early Termination) | 
| Change From Screening Period to Randomization Baseline in SF-36v2 Health Survey Score | SF-36v2 Health Survey is a self-administered questionnaire consisting of 36 questions, measuring 8 health aspects; physical functioning, role limitations due to physical problems, social functioning, bodily pain, mental health, role limitations due to emotional problems, vitality, and general health perception. These domains also combine to form two component summary scores evaluating mental health and physical health. The minimum score is 0 and the maximum score is 100. A higher score indicate a better health state. | Screening, Randomization Baseline | 
| Change From Randomization Baseline to the End of Double-Blind Week 12 (or Final Visit) in SF-36v2 Health Survey | SF-36v2 Health Survey is a self-administered questionnaire consisting of 36 questions, measuring 8 health aspects; physical functioning, role limitations due to physical problems, social functioning, bodily pain, mental health, role limitations due to emotional problems, vitality, and general health perception. These domains also combine to form two component summary scores evaluating mental health and physical health. The minimum score is 0 and the maximum score is 100. A higher score indicate a better health state. | Randomization Baseline, Week 12 | 
| Change From Screening Period to End of Double-Blind Week 12 (or Final Visit) in SF-36v2 Health Survey | SF-36v2 Health Survey is a self-administered questionnaire consisting of 36 questions, measuring 8 health aspects; physical functioning, role limitations due to physical problems, social functioning, bodily pain, mental health, role limitations due to emotional problems, vitality, and general health perception. These domains also combine to form two component summary scores evaluating mental health and physical health. The minimum score is 0 and the maximum score is 100. A higher score indicate a better health state. | Screening, Week 12 | 
| 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 | The EQ 5D Health Questionnaire is a self completion standardized instrument for use as a measure of health-related quality of life in terms of a single index value or utility score that consisted of 5 dimensions (mobility, self-care, usual activities, pain/discomfort, anxiety/depression) each of which was rated on a 3-point response scale (no problems/some or moderate problems/extreme problems), and the scores are combined to form a single index utility value between 0 and 1 with higher scores indicating better health. | Screening, Week 6 (or Early Termination) | 
| Change From Screening Period to the End of Open-Label Titration Period in Participant Assessment of Overall Health State Using the EQ-5D VAS | The EQ-5D consists of a standard vertical 20cm visual analogue scale (EQ VAS), for recording a participant's rating for their current health related quality of life state; the scale went from 0 (worst imaginable health state) to 100 (best imaginable health state). Participants were asked to draw a line on the scale to indicate how good or bad your own health is today, in your opinion. | 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 | Self-completion standardized instrument for use as a measure of health-related quality of life in terms of a single index value or utility score that consisted of 5 dimensions (mobility, self-care, usual activities, pain/discomfort, anxiety/depression) each of which was rated on a 3-point response scale (no problems/some or moderate problems/extreme problems), and the scores are combined to form a single index utility value between 0 and 1 with higher scores indicating better health | Screening, Randomization Baseline | 
| Change From Screening Period to Randomization Baseline in Participant Assessment of Overall Health State Using the EQ-5D VAS | The EQ-5D consists of a standard vertical 20cm visual analogue scale (EQ VAS), for recording a participant's rating for their current health related quality of life state; the scale went from 0 (worst imaginable health state) to 100 (best imaginable health state). Participants were asked to draw a line on the scale to indicate how good or bad your own health is today, in your opinion. | 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 EQ-5D Summary Index | Self-completion standardized instrument for use as a measure of health-related quality of life in terms of a single index value or utility score that consisted of 5 dimensions (mobility, self-care, usual activities, pain/discomfort, anxiety/depression) each of which was rated on a 3-point response scale (no problems/some or moderate problems/extreme problems), and the scores are combined to form a single index utility value between 0 and 1 with higher scores indicating better health | Randomization Baseline, Week 12 | 
| 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 | The EQ-5D consists of a standard vertical 20cm visual analogue scale (EQ VAS), for recording a participant's rating for their current health related quality of life state; the scale went from 0 (worst imaginable health state) to 100 (best imaginable health state). Participants were asked to draw a line on the scale to indicate how good or bad your own health is today, in your opinion. | 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 | Self-completion standardized instrument for use as a measure of health-related quality of life in terms of a single index value or utility score that consisted of 5 dimensions (mobility, self-care, usual activities, pain/discomfort, anxiety/depression) each of which was rated on a 3-point response scale (no problems/some or moderate problems/extreme problems), and the scores are combined to form a single index utility value between 0 and 1 with higher scores indicating better health. | 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 | The EQ-5D consists of a standard vertical 20cm visual analogue scale (EQ VAS), for recording a participant's rating for their current health related quality of life state; the scale went from 0 (worst imaginable health state) to 100 (best imaginable health state). Participants were asked to draw a line on the scale to indicate how good or bad your own health is today, in your opinion. | Screening, Week 12 | 
| 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 | A self-reported measure of work productivity and impairment that yields 4 scores: Absenteeism (work time missed); Presenteeism (impairment at work/reduced on the job effectiveness); work productivity loss (overall work impairment /absenteeism+presenteeism); and activity impairment. work time missed - a measure of absenteeism, calculated as work time missed due to health problem (question 2) as a proportion of hours actually worked (question 4). impairment while working - a measure of presenteeism, the degree to which health problem impacted work (question 5). overall work impairment - a measure of overall work productivity loss due to health problem (absenteeism+presenteeism). activity impairment - a measure of the degree to which health problem has affected ability to do regular activities other than work at a job (question 6). Each score is expressed as a percentage (0-100%) with higher numbers indicating greater impairment and less productivity. | Screening, Week 6 (or Early Termination) | 
| 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 | A self-reported measure of work productivity and impairment that yields 4 scores: Absenteeism (work time missed); Presenteeism (impairment at work/reduced on the job effectiveness); work productivity loss (overall work impairment/absenteeism+presenteeism); and activity impairment. work time missed - a measure of absenteeism, calculated as work time missed due to health problem (question 2) as a proportion of hours actually worked (question 4). impairment while working - a measure of presenteeism, the degree to which health problem impacted work (question 5). overall work impairment - a measure of overall work productivity loss due to health problem (absenteeism+presenteeism). activity impairment - a measure of the degree to which health problem has affected ability to do regular activities other than work at a job (question 6). Each score is expressed as a percentage (0-100%) with higher numbers indicating greater impairment and less productivity. | 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 | A self-reported measure of work productivity and impairment that yields 4 scores: Absenteeism (work time missed); Presenteeism (impairment at work/reduced on the job effectiveness); work productivity loss (overall work impairment/absenteeism+presenteeism); and activity impairment. % work time missed - a measure of absenteeism, calculated as work time missed due to health problem (question 2) as a proportion of hours actually worked (question 4). Each score is expressed as a percentage (0-100%) with higher numbers indicating greater impairment and less productivity. | 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 Impairment Due to Low Back Pain | A self-reported measure of work productivity and impairment that yields 4 scores: Absenteeism (work time missed); Presenteeism (impairment at work/reduced on the job effectiveness); work productivity loss (overall work impairment/absenteeism+presenteeism); and activity impairment. % impairment while working - a measure of presenteeism, the degree to which health problem impacted work (question 5). Each score is expressed as a percentage (0-100%) with higher numbers indicating greater impairment and less productivity. | 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 Overall Work Impairment Due to Low Back Pain | A self-reported measure of work productivity and impairment that yields 4 scores: Absenteeism (work time missed); Presenteeism (impairment at work/reduced on the job effectiveness); work productivity loss (overall work impairment/absenteeism+presenteeism); and activity impairment. % overall work impairment - a measure of overall work productivity loss due to health problem (absenteeism+presenteeism). Each score is expressed as a percentage (0-100%) with higher numbers indicating greater impairment and less productivity. | 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 | A self-reported measure of work productivity and impairment that yields 4 scores: Absenteeism (work time missed); Presenteeism (impairment at work/reduced on the job effectiveness); work productivity loss (overall work impairment/absenteeism+presenteeism); and activity impairment. % activity impairment - a measure of the degree to which health problem has affected ability to do regular activities other than work at a job (question 6). Each score is expressed as a percentage (0-100%) with higher numbers indicating greater impairment and less productivity. | 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 | A self-reported measure of work productivity and impairment that yields 4 scores: Absenteeism (work time missed); Presenteeism (impairment at work/reduced on the job effectiveness); work productivity loss (overall work impairment/absenteeism+presenteeism); and activity impairment. % work time missed - a measure of absenteeism, calculated as work time missed due to health problem (question 2) as a proportion of hours actually worked (question 4). Each score is expressed as a percentage (0-100%) with higher numbers indicating greater impairment and less productivity. | 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 Impairment Due to Low Back Pain | A self-reported measure of work productivity and impairment that yields 4 scores: Absenteeism (work time missed); Presenteeism (impairment at work/reduced on the job effectiveness); work productivity loss (overall work impairment/absenteeism+presenteeism); and activity impairment. % impairment while working - a measure of presenteeism, the degree to which health problem impacted work (question 5). Each score is expressed as a percentage (0-100%) with higher numbers indicating greater impairment and less productivity. | 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 Overall Work Impairment Due to Low Back Pain | A self-reported measure of work productivity and impairment that yields 4 scores: Absenteeism (work time missed); Presenteeism (impairment at work/reduced on the job effectiveness); work productivity loss (overall work impairment/absenteeism+presenteeism); and activity impairment. % overall work impairment - a measure of overall work productivity loss due to health problem (absenteeism+presenteeism). Each score is expressed as a percentage (0-100%) with higher numbers indicating greater impairment and less productivity. | 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 | A self-reported measure of work productivity and impairment that yields 4 scores: Absenteeism (work time missed); Presenteeism (impairment at work/reduced on the job effectiveness); work productivity loss (overall work impairment/absenteeism+presenteeism); and activity impairment. % activity impairment - a measure of the degree to which health problem has affected ability to do regular activities other than work at a job (question 6). Each score is expressed as a percentage (0-100%) with higher numbers indicating greater impairment and less productivity. | 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 | Question 3a = In the past 4 weeks, have you been hospitalized due to chronic low back pain or any medication used for chronic low back pain? | Screening, Week 6 (or Early Termination) | 
| Percentage of Participants With Shift From Screening Period to Randomization Baseline in Hospitalization Because of Low Back Pain as Assessed Using the HRU Questionnaire | Question 3a = In the past 4 weeks, have you been hospitalized due to chronic low back pain or any medication used for chronic low back pain? | 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 | Question 1: number of office visits directly related to chronic low back pain or any medication used for chronic low back pain. | Screening, Randomization Baseline | 
| Change From Screening to Randomization Baseline in HRU Questionnaire: Money Spent on Physical Treatments in Past 4 Weeks | Question 2: Money (dollars) spent out-of-pocket on physical treatments in the past 4 weeks to manage chronic low back pain | Screening, Randomization Baseline | 
| Change From Screening to Randomization Baseline in HRU Questionnaire: Nights Stayed in Hospital | Question 3b: nights stayed in the hospital, if answer to Q3a was yes. | 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 | Question 1: number of office visits directly related to chronic low back pain or any medication used for chronic low back pain. | Screening, Week 6 (or Early Termination) | 
| Change From Screening to End of Open-Label Titration Period in HRU Questionnaire: Money Spent on Physical Treatments in Past 4 Weeks | Question 2: Money (dollars) spent out-of-pocket on physical treatments in the past 4 weeks to manage chronic low back pain | Screening, Week 6 (or Early Termination) | 
| Change From Screening to End of Open-Label Titration Period in HRU Questionnaire: Nights Stayed in Hospital | Question 3b: nights stayed in the hospital, if answer to Q3a was yes. | 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 | Question 3a = In the past 4 weeks, have you been hospitalized due to chronic low back pain or any medication used for chronic low back pain? | Randomization Baseline, Weeks 4, 8, and 12 (or Early Termination) | 
| 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 | Question 1: number of office visits directly related to chronic low back pain or any medication used for chronic 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 HRU Questionnaire: Money Spent on Treatments | Question 2: money (dollars) spent out-of-pocket on physical treatments in the past 4 weeks to manage chronic 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 HRU Questionnaire: Nights Spent in Hospital | Question 3b: nights stayed in the 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 | Question 3a = In the past 4 weeks, have you been hospitalized due to chronic low back pain or any medication used 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: Number of Office Visits Related or Medication Used for Chronic Low Back Pain | Question 1: number of office visits directly related to chronic low back pain or any medication used 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: Money Spent on Treatment for Chronic Low Back Pain | Question 2: money (dollars) spent out-of-pocket on physical treatments in the past 4 weeks to manage 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 | Question 3b: nights stayed in the hospital | 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 | 
| Median Oxycodone Duration of Titration During the Open-Label Titration Period |  | Open-Label Period | 
| Mean Oxycodone Average Daily Dose During the Double-Blind Treatment Period |  | Double-Blind Period | 
| Mean Oxycodone Duration of Treatment During the Double-Blind Treatment Period |  | Double-Blind Period | 
| Median Oxycodone Average Daily Dose During the Double-Blind Treatment Period |  | Double-Blind Period | 
| 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 | Observed steady-state plasma concentration (Cobs) of oxycodone and noroxycodone. | Blood samples were taken within +/-4 hours of the morning dose of ALO-02 at Week 6/Early Termination, Randomization Baseline | 
| Naltrexone and 6-β-naltrexol Observed Steady-State Plasma Concentration During the Titration Period | Cobs of naltrexone and 6-β-naltrexol | 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 | Observed steady-state plasma concentration (Cobs) of oxycodone and noroxycodone | Blood samples were taken within +/-4 hours of the morning dose of study drug at Randomization Baseline, Weeks 4, 8, and 12 | 
| Naltrexone and 6-β-naltrexol Observed Steady-State Plasma Concentration During the Double Blind Treatment Period | Observed steady-state plasma concentration (Cobs) of naltrexone and 6-β-naltrexol | Blood samples were taken within +/-4 hours of the morning dose of study drug at Randomization Baseline, Weeks 4, 8, and 12 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
oxycodone, naltrexone, chronic pain, low back pain