Low Back Pain
Conditions
Keywords
chronic low back pain, hydrocodone bitartrate, opioids
Brief summary
The primary objective of this study is to evaluate the efficacy of hydrocodone bitartrate extended-release tablets at doses of 30 to 90 mg every 12 hours compared with placebo in alleviating moderate to severe pain in patients with chronic low back pain. Patients may be opioid-naïve or opioid-experienced.
Detailed description
The study consisted of a screening period of approximately 7 to 14 days, an open label titration period of up to 6 weeks, and a double blind treatment period of 12 weeks. The objective of the open label titration period was to find the successful dose of hydrocodone extended release (ER) tablets that produced stable pain relief without unacceptable adverse events (AEs). Stable pain relief was defined as an average pain intensity (API) score over the previous 24 hours of 4 or less and a worst pain intensity (WPI) score of 6 or less on the 11-point numerical rating scale (NRS-11) (0=no pain to 10=worst pain imaginable) for either 4 consecutive days or 4 out of 7 consecutive days, while the same dose of study drug was maintained for up to 7 days. Scores for WPI and API were recorded daily in individual patient electronic diaries. Patients returned to the study center prior to each dose adjustment. The starting dose of hydrocodone ER tablets depended on whether the subject was opioid-naïve or opioid-experienced. Opioid-naïve participants started at a 15-mg dose of hydrocodone ER tablets every 12 hours. For opioid-experienced participants, the starting dose of hydrocodone ER tablets was to be approximately equivalent to 50% of the dose of opioid analgesic that they were receiving at screening and administered every 12 hours. Investigators switched participants from previous opioid therapy to hydrocodone ER tablets on the basis of predefined dose equivalents. Participants who met the criterion of a stabilized dose were randomly assigned into the 12 week, double-blind, placebo controlled treatment period on the final day of the open label titration period (baseline visit). Participants began treatment with double blind study drug at the effective dose of hydrocodone ER tablets achieved during the titration period or matching placebo. Rescue medication was permitted in addition to the study drug during the double blind treatment period. Participants who participated in the study in compliance with the protocol and complete 12 weeks of double-blind treatment with study drug, were considered to have completed the study and could have been eligible to enroll in a 6-month open-label study (study C32337/3104, NCT01922739).
Interventions
DRUGHydrocodone ER
During the open-label, titration period, all participants were administered hydrocodone ER tablets at dosages of 15, 30, 45, 60, or 90 mg every 12 hours to identify a dosage deemed successful for managing their pain. Hydrocodone ER was taken by participants randomized to the hydrocodone ER treatment arm during the double-blind treatment period at the dose level identified during the titration period. Participants were instructed to take tablets with a glass of water on an empty stomach at least 1 hour before or 2 hours after eating.
DRUGPlacebo
Placebo matching the active drug dose identified during the titration period was taken by participants randomized to the placebo treatment arm during the double-blind treatment period. Participants were instructed to take intervention with a glass of water on an empty stomach at least 1 hour before or 2 hours after eating.
Sponsors
Teva Branded Pharmaceutical Products R&D, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* The patient has had moderate to severe chronic low back pain for at least 3 months duration before screening. * The patient is able to speak English and is willing to provide written informed consent, including a written opioid agreement, to participate in this study. * The patient is willing and able to successfully self-administer the study drug, comply with study restrictions, complete the electronic diary, and return to the study center for scheduled study visits, as specified in the protocol. * The patient is 18 through 80 years of age at the time of screening. * Women of childbearing potential (not surgically sterile or 2 years postmenopausal) must use a medically accepted method of contraception, agree to continue use of this method for the duration of the study and for 30 days after participation in the study, and have a negative pregnancy test at screening. - Acceptable methods of contraception include barrier method with spermicide, intrauterine device (IUD), or steroidal contraceptive (oral, transdermal, implanted, and injected) in conjunction with a barrier method. NOTE: A woman will be considered surgically sterile if she has had a tubal ligation, hysterectomy, bilateral salpingo-oophorectomy or bilateral oophorectomy, or hysterectomy with bilateral salpingo-oophorectomy. * Other criteria apply.
Exclusion criteria
* The patient is taking a total of more than 135 mg/day of oxycodone, or equivalent, during the 14 days before screening. * The patient's primary painful condition under study is related to any source of chronic pain other than low back pain. * The patient has radicular (nerve compression) pain or another type of purely neuropathic pain. * The patient has known or suspected hypersensitivities, allergies, or other contraindications to any ingredient in the study drug. * The patient has a recent history (within 5 years) or current evidence of alcohol or other substance abuse, with the exception of nicotine. * The patient has medical or psychiatric disease that, in the opinion of the investigator, would compromise collected data. * Other criteria apply.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to Week 12 of the Treatment Period in Weekly Average of Daily Worst Pain Intensity (WPI) | Days -6 to 0 of Treatment Period (baseline), Week 12 of Treatment Period | The WPI was recorded daily by participants in an electronic diary using an 11-point numerical rating scale (NRS-11), a Likert-type scale in which 0=no pain and 10=the worst pain imaginable. Participants selected the number that best described their worst pain intensity over the last 24 hours. Weekly WPI scores averaged daily scores collected over the previous 7 days for each analysis visit. Negative change from baseline scores indicate improvement in pain control. The analysis included WPI data observed before discontinuation of study drug and was based on the multiple imputations (MI) method to handle missing scores at week 12. Consistent with the recommendations of the National Academy of Sciences (NAS) report (Panel on Handling Missing Data in Clinical Trials 2010), the MI method includes an assumption of missing at random (MAR) and takes into account a potential bias toward the active-drug treatment group for patients who discontinued study drug because of adverse events. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Kaplan-Meier Estimates for Time to Loss of Efficacy | Day 1 to Week 12 of Treatment Period | Time to loss of efficacy was defined as discontinuation of study drug for lack of efficacy or the start of excessive rescue medication while taking study drug. Excessive rescue medication usage was defined as 10 or more days of rescue medication usage in any 14 consecutive days at a total of 15 mg (hydrocodone-equivalent) or higher each day during the post 2-week tapering period of the double-blind treatment period. |
| Percentage of Participants With a 30% or Greater Increase in Weekly Average Pain Intensity (API) From Baseline to Week 12 Visit, and an Average API Score of 5 or Higher at Week 12 | Days -6 to 0 of Treatment Period (baseline), Week 12 | The API over the last 24 hours was recorded daily by participants in an electronic diary using an 11-point numerical rating scale (NRS-11), a Likert-type scale in which 0=no pain and 10=the worst pain imaginable. Participants selected the number that best described the average pain intensity over the last 24 hours. Weekly API scores averaged daily scores collected over the previous 7 days for each analysis visit. |
| Change From Baseline to Final On-Treatment Visit in Roland Morris Disability Questionnaire (RMDQ) Score | Days 7-14 of Titration Period (baseline), Week 12 or end of study visit during the Treatment Period | The RMDQ is a patient-rated, 24-question evaluation used to assess acute disability associated with low back pain. Each question is answered with a YES or NO response, and each YES response is given 1 point. Scores on the RMDQ range from 0 to 24, with higher scores indicating greater disability. Negative change from baseline scores indicate improvement in level of disability. |
| Participants With Adverse Events During Open-Label Titration and Double-Blind Treatment Periods | Day 1 of Titration Period up to Week 12 of Treatment Period (maximum treatment duration was 127 days) | An adverse event (AE) was defined in the protocol as any untoward medical occurrence that develops or worsens in severity during the conduct of a clinical study and does not necessarily have a causal relationship to the study drug. Severity was rated by the investigator on a scale of mild, moderate and severe, with severe= an inability to carry out usual activities. Relation of AE to treatment was determined by the investigator. Serious AEs include death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, OR an important medical event that jeopardized the patient and required medical intervention to prevent the previously listed serious outcomes. |
| Participants With Clinically Significant Hearing Changes From Baseline to Final Assessment in Pure Tone Audiometry Test Results | Days 7-14 of Titration Period (baseline), Day 0 of Treatment Period (last day of Titration Period), Week 12 or end of study visit during the Treatment Period | Pure tone audiometry was performed by a qualified audiologist and was not done at the study center. During the test, the patient wore headphones and was seated in a quiet room; trained personnel manipulated the audiometry equipment to test the patient's hearing. For serial audiograms, the criteria for a clinically significant (CS) hearing change were based on the guidance from the American Speech-Language Hearing Association (ASHA) 1994 (Konrad-Martin et al 2005). These criteria included the following: greater than 20 decibels (dB) pure tone threshold shift at 1 frequency; greater than 10 dB shift at 2 consecutive test frequencies; or threshold response shifting to no response at 3 consecutive test frequencies. |
| Change From Baseline to Week 12 of the Treatment Period in Weekly Average Pain Intensity (API) | Days -6 to 0 of Treatment Period (baseline), Week 12 | The API over the last 24 hours was recorded daily by patients in an electronic diary using an 11-point numerical rating scale (NRS-11), a Likert-type scale in which 0=no pain and 10=the worst pain imaginable. Participants selected the number that best described the average pain intensity over the last 24 hours. Weekly API scores averaged daily scores collected over the previous 7 days for each analysis visit. Negative change from baseline scores indicate improvement in pain control. The analysis included API data observed before discontinuation of study drug and was based on the MI method to handle missing scores at week 12. Consistent with the recommendations of the National Academy of Sciences (NAS) report (Panel on Handling Missing Data in Clinical Trials 2010), the MI method includes an assumption of missing at random (MAR) and takes into account a potential bias toward the active-drug treatment group for patients who discontinued study drug because of adverse events. |
| Clinical Opiate Withdrawal Scales (COWS) Total Scores During the Double-Blind Treatment Period | Weeks 1, 2, 4 and Endpoint of the Treatment Period | COWS is a clinician-rated scale used to measure a participant's signs and symptoms of withdrawal from opiates, with ratings based only on apparent relationship to withdrawal. The COWS was performed at weeks 1, 2, 4, and 12 (double blind treatment period) or early termination. The scale contained 11 signs/symptoms whose intensity the clinician rated on a scale of 0 to 4 or 5. A total score was calculated as the sum of the responses to the 11 signs/symptoms for a total range of 0-48. Withdrawal severity was classified, based on the total score, as follows: * 0 to 4=normal * 5 to 12=mild * 13 to 24=moderate * 25 to 36=moderately severe * 36=severe |
| Participants With Potentially Clinically Significant Abnormal Laboratory Values During the Double-Blind Treatment Period | Day 1 up to Week 12 of the Treatment Period | Data represents participants with potentially clinically significant abnormal serum chemistry, hematology and urinalysis values. Significance criteria: * Blood urea nitrogen: \>=10.71 mmol/L * Creatinine: \>=177 μmol/L * Uric acid: M\>=625, F\>=506 μmol/L * Alanine aminotransferase (ALT): \>=3\* upper limit of normal (ULN) * Gamma-glutamyl transpeptidase (GGT): \>=3\* upper limit of normal (ULN) * Serum white blood cells: \<=3.0 \* 10\^9/L * Hemoglobin: M\<=115, F\<=95 g/dL * Hematocrit: M\<0.37, F\<0.32 L/L * Eosinophils: \>=10.0 % * Absolute neutrophils: \<=1.0 \* 10\^9/L * Urinalysis: Glucose: \>=2 unit increase from baseline |
| Participants With Potentially Clinically Significant Abnormal Vital Sign Values During the Double-Blind Treatment Period | Day 1 to Week 12 of the Treatment Period | Data represents participants with potentially clinically significant (PCS) vital sign values. Significance criteria * Pulse - high: \>=120 and increase of \>= 15 beats/minute from baseline * Pulse - low: \<=50 and decrease of \>=15 beats/minute * Systolic blood pressure - high: \>=180 and increase \>=20 mmHg * Systolic blood pressure - low: \<=90 and decrease \>=20 mmHg * Diastolic blood pressure - high: \>=105 and increase of \>=15 mmHg * Diastolic blood pressure - low: \<=50 and decrease of \>=15 mmHg |
| Participants With Potentially Clinically Significant Abnormal Electrocardiogram Findings During the Double-Blind Treatment Period | Final study visit (week 12 or end of treatment visit) | Data represents the number of participants with potentially clinically significant (PCS) electrocardiogram findings on the final study visit. |
| Subjective Opiate Withdrawal Scales (SOWS) Total Scores During the Double-Blind Treatment Period | Weeks 1, 2, 4 and Endpoint of the Treatment Period | The results of the SOWS were collected in the e-diary daily during the first 4 weeks of the double blind treatment period and then during clinic visits at week 12 or early termination. The SOWS was a self-administered questionnaire used to measure a participant's signs and symptoms of withdrawal from opiates. The scale contained 16 symptoms (such as my nose is running; I feel restless), the participant rated the intensity on a scale of 0 (not at all) to 4 (extremely) for a total score of 0-64. The daily total score for the first 4 weeks was the largest score observed during the time period preceding that visit. For example, the week 1 score for each participant was the largest total score on any day between baseline and the night before the week 1 visit; the week 4 score for each participant was the largest score observed between the week 2 visit and the night before the week 4 visit. |
Countries
United States
Participant flow
Recruitment details
A total of 845 patients with moderate to severe chronic low back pain were screened at 78 centers in the U.S.
Pre-assignment details
Of the 625 patients enrolled, 2 patients withdrew consent before taking any study drug. Of 623 patients who were enrolled and received study drug, 371 patients achieved a successful dose of hydrocodone extended-release (ER) tablets and were randomly assigned to receive hydrocodone ER or placebo during the double-blind treatment period
Participants by arm
| Arm | Count |
|---|---|
| Placebo (Double-blind Treatment Period) Participants were administered placebo tablets every 12 hours that matched the dosage deemed successful for managing their pain during the titration period. A step wise, double-blind tapering schedule was implemented during the first 2 weeks of the 12 week, double blind, placebo controlled treatment period to reduce the risk of withdrawal effects in patients randomly assigned to placebo. | 180 |
| Hydrocodone ER (Double-blind Treatment Period) Participants were administered extended-release hydrocodone tablets at a dosage deemed successful for managing their pain during the titration period. Dosages of 15, 30, 45, 60, or 90 mg every 12 hours were given for 12 weeks during the double-blind period. | 191 |
| Total | 371 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Double-blind Treatment Period (12 Weeks) | Adverse Event | 0 | 9 | 15 |
| Double-blind Treatment Period (12 Weeks) | Dropped out prior to dosing | 0 | 1 | 0 |
| Double-blind Treatment Period (12 Weeks) | Lack of Efficacy | 0 | 17 | 5 |
| Double-blind Treatment Period (12 Weeks) | Lost to Follow-up | 0 | 1 | 2 |
| Double-blind Treatment Period (12 Weeks) | Noncompliance to study drug admin | 0 | 2 | 2 |
| Double-blind Treatment Period (12 Weeks) | Noncompliance with study procedures | 0 | 2 | 1 |
| Double-blind Treatment Period (12 Weeks) | Other | 0 | 1 | 3 |
| Double-blind Treatment Period (12 Weeks) | Pregnancy | 0 | 1 | 0 |
| Double-blind Treatment Period (12 Weeks) | Protocol Violation | 0 | 9 | 7 |
| Double-blind Treatment Period (12 Weeks) | Withdrawal by Subject | 0 | 7 | 9 |
| Open-label Titration Period | Adverse Event | 68 | 0 | 0 |
| Open-label Titration Period | Dropped out prior to dosing | 2 | 0 | 0 |
| Open-label Titration Period | Lack of Efficacy | 31 | 0 | 0 |
| Open-label Titration Period | Lost to Follow-up | 5 | 0 | 0 |
| Open-label Titration Period | Noncompliance to study drug admin | 11 | 0 | 0 |
| Open-label Titration Period | Noncompliance with study procedures | 8 | 0 | 0 |
| Open-label Titration Period | Noncompliance with study rescue meds | 2 | 0 | 0 |
| Open-label Titration Period | Other | 76 | 0 | 0 |
| Open-label Titration Period | Pregnancy | 2 | 0 | 0 |
| Open-label Titration Period | Protocol Violation | 18 | 0 | 0 |
| Open-label Titration Period | Withdrawal by Subject | 31 | 0 | 0 |
Baseline characteristics
| Characteristic | Placebo (Double-blind Treatment Period) | Hydrocodone ER (Double-blind Treatment Period) | Total |
|---|---|---|---|
| Age, Continuous | 51.8 years STANDARD_DEVIATION 12.51 | 51.7 years STANDARD_DEVIATION 13.48 | 51.8 years STANDARD_DEVIATION 13 |
| Age, Customized <= 65 years | 154 Participants | 156 Participants | 310 Participants |
| Age, Customized > 65 years | 26 Participants | 35 Participants | 61 Participants |
| Average Daily Hydrocodone Equivalent Dose | 18.2 mg STANDARD_DEVIATION 28.55 | 22.1 mg STANDARD_DEVIATION 30.18 | 20.2 mg STANDARD_DEVIATION 29.43 |
| Body Mass Index | 31.5 kg/m^2 STANDARD_DEVIATION 8.22 | 31.3 kg/m^2 STANDARD_DEVIATION 7.37 | 31.4 kg/m^2 STANDARD_DEVIATION 7.78 |
| Duration of Opioid Therapy | 2.9 years STANDARD_DEVIATION 3.76 | 3.5 years STANDARD_DEVIATION 4.85 | 3.2 years STANDARD_DEVIATION 4.37 |
| Duration Since Diagnosis of Chronic Low Back Pain | 11.5 years STANDARD_DEVIATION 10.35 | 11.3 years STANDARD_DEVIATION 10.29 | 11.4 years STANDARD_DEVIATION 10.31 |
| Ethnicity Hispanic or Latino | 23 Participants | 24 Participants | 47 Participants |
| Ethnicity Non-Hispanic and non-Latino | 156 Participants | 167 Participants | 323 Participants |
| Ethnicity Unknown | 1 Participants | 0 Participants | 1 Participants |
| Participant Opioid Status Opioid-experienced | 75 Participants | 81 Participants | 156 Participants |
| Participant Opioid Status Opioid-naive | 105 Participants | 110 Participants | 215 Participants |
| Race American Indian or Alaska Native | 2 Participants | 2 Participants | 4 Participants |
| Race Asian | 8 Participants | 13 Participants | 21 Participants |
| Race Black | 41 Participants | 39 Participants | 80 Participants |
| Race Native Hawaiian or other Pacific Islander | 0 Participants | 1 Participants | 1 Participants |
| Race Other | 0 Participants | 3 Participants | 3 Participants |
| Race White | 129 Participants | 133 Participants | 262 Participants |
| Sex: Female, Male Female | 92 Participants | 97 Participants | 189 Participants |
| Sex: Female, Male Male | 88 Participants | 94 Participants | 182 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 211 / 623 | 41 / 179 | 58 / 191 |
| serious Total, serious adverse events | 10 / 623 | 3 / 179 | 3 / 191 |
Outcome results
Primary
Change From Baseline to Week 12 of the Treatment Period in Weekly Average of Daily Worst Pain Intensity (WPI)
The WPI was recorded daily by participants in an electronic diary using an 11-point numerical rating scale (NRS-11), a Likert-type scale in which 0=no pain and 10=the worst pain imaginable. Participants selected the number that best described their worst pain intensity over the last 24 hours. Weekly WPI scores averaged daily scores collected over the previous 7 days for each analysis visit. Negative change from baseline scores indicate improvement in pain control. The analysis included WPI data observed before discontinuation of study drug and was based on the multiple imputations (MI) method to handle missing scores at week 12. Consistent with the recommendations of the National Academy of Sciences (NAS) report (Panel on Handling Missing Data in Clinical Trials 2010), the MI method includes an assumption of missing at random (MAR) and takes into account a potential bias toward the active-drug treatment group for patients who discontinued study drug because of adverse events.
Time frame: Days -6 to 0 of Treatment Period (baseline), Week 12 of Treatment Period
Population: The full analysis set, which includes all randomized participants who received at least 1 dose of study drug and had at least 1 post-baseline efficacy observation.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Double-blind Treatment Period) | Change From Baseline to Week 12 of the Treatment Period in Weekly Average of Daily Worst Pain Intensity (WPI) | 0.71 units on a scale | Standard Error 0.145 |
| Hydrocodone ER (Double-blind Treatment Period) | Change From Baseline to Week 12 of the Treatment Period in Weekly Average of Daily Worst Pain Intensity (WPI) | 0.07 units on a scale | Standard Error 0.134 |
Comparison: The least squares means of the change from baseline to week 12 in WPI were compared between the active drug and placebo treatment groups.p-value: <0.00195% CI: [0.26, 1]ANCOVA
Secondary
Change From Baseline to Final On-Treatment Visit in Roland Morris Disability Questionnaire (RMDQ) Score
The RMDQ is a patient-rated, 24-question evaluation used to assess acute disability associated with low back pain. Each question is answered with a YES or NO response, and each YES response is given 1 point. Scores on the RMDQ range from 0 to 24, with higher scores indicating greater disability. Negative change from baseline scores indicate improvement in level of disability.
Time frame: Days 7-14 of Titration Period (baseline), Week 12 or end of study visit during the Treatment Period
Population: Full analysis set, including participants with RMDQ score for the final on-treatment visit.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Double-blind Treatment Period) | Change From Baseline to Final On-Treatment Visit in Roland Morris Disability Questionnaire (RMDQ) Score | -1.9 units on a scale | Standard Deviation 4.47 |
| Hydrocodone ER (Double-blind Treatment Period) | Change From Baseline to Final On-Treatment Visit in Roland Morris Disability Questionnaire (RMDQ) Score | -1.5 units on a scale | Standard Deviation 4.7 |
p-value: 0.55795% CI: [-1.2, 0.65]ANCOVA
Secondary
Change From Baseline to Week 12 of the Treatment Period in Weekly Average Pain Intensity (API)
The API over the last 24 hours was recorded daily by patients in an electronic diary using an 11-point numerical rating scale (NRS-11), a Likert-type scale in which 0=no pain and 10=the worst pain imaginable. Participants selected the number that best described the average pain intensity over the last 24 hours. Weekly API scores averaged daily scores collected over the previous 7 days for each analysis visit. Negative change from baseline scores indicate improvement in pain control. The analysis included API data observed before discontinuation of study drug and was based on the MI method to handle missing scores at week 12. Consistent with the recommendations of the National Academy of Sciences (NAS) report (Panel on Handling Missing Data in Clinical Trials 2010), the MI method includes an assumption of missing at random (MAR) and takes into account a potential bias toward the active-drug treatment group for patients who discontinued study drug because of adverse events.
Time frame: Days -6 to 0 of Treatment Period (baseline), Week 12
Population: The full analysis set, which includes all randomized participants who received at least 1 dose of study drug and had at least 1 post-baseline efficacy observation.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Double-blind Treatment Period) | Change From Baseline to Week 12 of the Treatment Period in Weekly Average Pain Intensity (API) | 0.57 units on a scale | Standard Error 0.126 |
| Hydrocodone ER (Double-blind Treatment Period) | Change From Baseline to Week 12 of the Treatment Period in Weekly Average Pain Intensity (API) | 0.02 units on a scale | Standard Error 0.116 |
Comparison: The least squares means of the change from baseline to week 12 in API were compared between the active drug and placebo treatment groups.p-value: <0.00195% CI: [0.25, 0.91]ANCOVA
Secondary
Clinical Opiate Withdrawal Scales (COWS) Total Scores During the Double-Blind Treatment Period
COWS is a clinician-rated scale used to measure a participant's signs and symptoms of withdrawal from opiates, with ratings based only on apparent relationship to withdrawal. The COWS was performed at weeks 1, 2, 4, and 12 (double blind treatment period) or early termination. The scale contained 11 signs/symptoms whose intensity the clinician rated on a scale of 0 to 4 or 5. A total score was calculated as the sum of the responses to the 11 signs/symptoms for a total range of 0-48. Withdrawal severity was classified, based on the total score, as follows: * 0 to 4=normal * 5 to 12=mild * 13 to 24=moderate * 25 to 36=moderately severe * 36=severe
Time frame: Weeks 1, 2, 4 and Endpoint of the Treatment Period
Population: Full analysis set. Participants contributing to each time point are listed in the time point label.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo (Double-blind Treatment Period) | Clinical Opiate Withdrawal Scales (COWS) Total Scores During the Double-Blind Treatment Period | Week 1 | 0.9 units on a scale | Standard Deviation 1.66 |
| Placebo (Double-blind Treatment Period) | Clinical Opiate Withdrawal Scales (COWS) Total Scores During the Double-Blind Treatment Period | Week 2 | 0.8 units on a scale | Standard Deviation 1.52 |
| Placebo (Double-blind Treatment Period) | Clinical Opiate Withdrawal Scales (COWS) Total Scores During the Double-Blind Treatment Period | Week 4 | 0.8 units on a scale | Standard Deviation 1.33 |
| Placebo (Double-blind Treatment Period) | Clinical Opiate Withdrawal Scales (COWS) Total Scores During the Double-Blind Treatment Period | Endpoint | 0.9 units on a scale | Standard Deviation 1.49 |
| Hydrocodone ER (Double-blind Treatment Period) | Clinical Opiate Withdrawal Scales (COWS) Total Scores During the Double-Blind Treatment Period | Endpoint | 0.7 units on a scale | Standard Deviation 1.12 |
| Hydrocodone ER (Double-blind Treatment Period) | Clinical Opiate Withdrawal Scales (COWS) Total Scores During the Double-Blind Treatment Period | Week 1 | 0.8 units on a scale | Standard Deviation 1.33 |
| Hydrocodone ER (Double-blind Treatment Period) | Clinical Opiate Withdrawal Scales (COWS) Total Scores During the Double-Blind Treatment Period | Week 4 | 0.6 units on a scale | Standard Deviation 1.03 |
| Hydrocodone ER (Double-blind Treatment Period) | Clinical Opiate Withdrawal Scales (COWS) Total Scores During the Double-Blind Treatment Period | Week 2 | 0.7 units on a scale | Standard Deviation 1.13 |
Secondary
Kaplan-Meier Estimates for Time to Loss of Efficacy
Time to loss of efficacy was defined as discontinuation of study drug for lack of efficacy or the start of excessive rescue medication while taking study drug. Excessive rescue medication usage was defined as 10 or more days of rescue medication usage in any 14 consecutive days at a total of 15 mg (hydrocodone-equivalent) or higher each day during the post 2-week tapering period of the double-blind treatment period.
Time frame: Day 1 to Week 12 of Treatment Period
Population: The full analysis set, which includes all randomized participants who received at least 1 dose of study drug and had at least 1 post-baseline efficacy observation.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo (Double-blind Treatment Period) | Kaplan-Meier Estimates for Time to Loss of Efficacy | NA days |
| Hydrocodone ER (Double-blind Treatment Period) | Kaplan-Meier Estimates for Time to Loss of Efficacy | NA days |
p-value: 0.05995% CI: [0.5, 1.01]Wald chi-square
Secondary
Participants With Adverse Events During Open-Label Titration and Double-Blind Treatment Periods
An adverse event (AE) was defined in the protocol as any untoward medical occurrence that develops or worsens in severity during the conduct of a clinical study and does not necessarily have a causal relationship to the study drug. Severity was rated by the investigator on a scale of mild, moderate and severe, with severe= an inability to carry out usual activities. Relation of AE to treatment was determined by the investigator. Serious AEs include death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, OR an important medical event that jeopardized the patient and required medical intervention to prevent the previously listed serious outcomes.
Time frame: Day 1 of Titration Period up to Week 12 of Treatment Period (maximum treatment duration was 127 days)
Population: Safety analysis set (Titration Period) and Full analysis set (Treatment Period)
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo (Double-blind Treatment Period) | Participants With Adverse Events During Open-Label Titration and Double-Blind Treatment Periods | Any adverse event | 196 Participants |
| Placebo (Double-blind Treatment Period) | Participants With Adverse Events During Open-Label Titration and Double-Blind Treatment Periods | Severe adverse event | 13 Participants |
| Placebo (Double-blind Treatment Period) | Participants With Adverse Events During Open-Label Titration and Double-Blind Treatment Periods | Treatment-related adverse event | 166 Participants |
| Placebo (Double-blind Treatment Period) | Participants With Adverse Events During Open-Label Titration and Double-Blind Treatment Periods | Deaths | 0 Participants |
| Placebo (Double-blind Treatment Period) | Participants With Adverse Events During Open-Label Titration and Double-Blind Treatment Periods | Serious adverse event | 6 Participants |
| Placebo (Double-blind Treatment Period) | Participants With Adverse Events During Open-Label Titration and Double-Blind Treatment Periods | Discontinued study drug treatment due to AE | 53 Participants |
| Hydrocodone ER (Double-blind Treatment Period) | Participants With Adverse Events During Open-Label Titration and Double-Blind Treatment Periods | Discontinued study drug treatment due to AE | 22 Participants |
| Hydrocodone ER (Double-blind Treatment Period) | Participants With Adverse Events During Open-Label Titration and Double-Blind Treatment Periods | Deaths | 0 Participants |
| Hydrocodone ER (Double-blind Treatment Period) | Participants With Adverse Events During Open-Label Titration and Double-Blind Treatment Periods | Any adverse event | 117 Participants |
| Hydrocodone ER (Double-blind Treatment Period) | Participants With Adverse Events During Open-Label Titration and Double-Blind Treatment Periods | Treatment-related adverse event | 81 Participants |
| Hydrocodone ER (Double-blind Treatment Period) | Participants With Adverse Events During Open-Label Titration and Double-Blind Treatment Periods | Severe adverse event | 5 Participants |
| Hydrocodone ER (Double-blind Treatment Period) | Participants With Adverse Events During Open-Label Titration and Double-Blind Treatment Periods | Serious adverse event | 4 Participants |
| Placebo (Double-blind Treatment Period) | Participants With Adverse Events During Open-Label Titration and Double-Blind Treatment Periods | Severe adverse event | 3 Participants |
| Placebo (Double-blind Treatment Period) | Participants With Adverse Events During Open-Label Titration and Double-Blind Treatment Periods | Treatment-related adverse event | 50 Participants |
| Placebo (Double-blind Treatment Period) | Participants With Adverse Events During Open-Label Titration and Double-Blind Treatment Periods | Deaths | 0 Participants |
| Placebo (Double-blind Treatment Period) | Participants With Adverse Events During Open-Label Titration and Double-Blind Treatment Periods | Discontinued study drug treatment due to AE | 7 Participants |
| Placebo (Double-blind Treatment Period) | Participants With Adverse Events During Open-Label Titration and Double-Blind Treatment Periods | Serious adverse event | 3 Participants |
| Placebo (Double-blind Treatment Period) | Participants With Adverse Events During Open-Label Titration and Double-Blind Treatment Periods | Any adverse event | 88 Participants |
| Hydrocodone ER (Double-blind Treatment Period) | Participants With Adverse Events During Open-Label Titration and Double-Blind Treatment Periods | Serious adverse event | 3 Participants |
| Hydrocodone ER (Double-blind Treatment Period) | Participants With Adverse Events During Open-Label Titration and Double-Blind Treatment Periods | Discontinued study drug treatment due to AE | 11 Participants |
| Hydrocodone ER (Double-blind Treatment Period) | Participants With Adverse Events During Open-Label Titration and Double-Blind Treatment Periods | Severe adverse event | 9 Participants |
| Hydrocodone ER (Double-blind Treatment Period) | Participants With Adverse Events During Open-Label Titration and Double-Blind Treatment Periods | Deaths | 0 Participants |
| Hydrocodone ER (Double-blind Treatment Period) | Participants With Adverse Events During Open-Label Titration and Double-Blind Treatment Periods | Any adverse event | 106 Participants |
| Hydrocodone ER (Double-blind Treatment Period) | Participants With Adverse Events During Open-Label Titration and Double-Blind Treatment Periods | Treatment-related adverse event | 67 Participants |
Secondary
Participants With Clinically Significant Hearing Changes From Baseline to Final Assessment in Pure Tone Audiometry Test Results
Pure tone audiometry was performed by a qualified audiologist and was not done at the study center. During the test, the patient wore headphones and was seated in a quiet room; trained personnel manipulated the audiometry equipment to test the patient's hearing. For serial audiograms, the criteria for a clinically significant (CS) hearing change were based on the guidance from the American Speech-Language Hearing Association (ASHA) 1994 (Konrad-Martin et al 2005). These criteria included the following: greater than 20 decibels (dB) pure tone threshold shift at 1 frequency; greater than 10 dB shift at 2 consecutive test frequencies; or threshold response shifting to no response at 3 consecutive test frequencies.
Time frame: Days 7-14 of Titration Period (baseline), Day 0 of Treatment Period (last day of Titration Period), Week 12 or end of study visit during the Treatment Period
Population: Safety analysis set (entire study), Full analysis set (treatment period)
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo (Double-blind Treatment Period) | Participants With Clinically Significant Hearing Changes From Baseline to Final Assessment in Pure Tone Audiometry Test Results | >= 1 CS value during study | 29 Participants |
| Placebo (Double-blind Treatment Period) | Participants With Clinically Significant Hearing Changes From Baseline to Final Assessment in Pure Tone Audiometry Test Results | >= CS value during open-label titration period | 13 Participants |
| Placebo (Double-blind Treatment Period) | Participants With Clinically Significant Hearing Changes From Baseline to Final Assessment in Pure Tone Audiometry Test Results | >= 1 CS during double-blind treatment period | NA Participants |
| Placebo (Double-blind Treatment Period) | Participants With Clinically Significant Hearing Changes From Baseline to Final Assessment in Pure Tone Audiometry Test Results | >=CS value at endpoint | NA Participants |
| Hydrocodone ER (Double-blind Treatment Period) | Participants With Clinically Significant Hearing Changes From Baseline to Final Assessment in Pure Tone Audiometry Test Results | >=CS value at endpoint | 8 Participants |
| Hydrocodone ER (Double-blind Treatment Period) | Participants With Clinically Significant Hearing Changes From Baseline to Final Assessment in Pure Tone Audiometry Test Results | >= 1 CS value during study | 10 Participants |
| Hydrocodone ER (Double-blind Treatment Period) | Participants With Clinically Significant Hearing Changes From Baseline to Final Assessment in Pure Tone Audiometry Test Results | >= 1 CS during double-blind treatment period | 8 Participants |
| Hydrocodone ER (Double-blind Treatment Period) | Participants With Clinically Significant Hearing Changes From Baseline to Final Assessment in Pure Tone Audiometry Test Results | >= CS value during open-label titration period | 5 Participants |
| Placebo (Double-blind Treatment Period) | Participants With Clinically Significant Hearing Changes From Baseline to Final Assessment in Pure Tone Audiometry Test Results | >=CS value at endpoint | 7 Participants |
| Placebo (Double-blind Treatment Period) | Participants With Clinically Significant Hearing Changes From Baseline to Final Assessment in Pure Tone Audiometry Test Results | >= CS value during open-label titration period | 2 Participants |
| Placebo (Double-blind Treatment Period) | Participants With Clinically Significant Hearing Changes From Baseline to Final Assessment in Pure Tone Audiometry Test Results | >= 1 CS during double-blind treatment period | 6 Participants |
| Placebo (Double-blind Treatment Period) | Participants With Clinically Significant Hearing Changes From Baseline to Final Assessment in Pure Tone Audiometry Test Results | >= 1 CS value during study | 8 Participants |
Secondary
Participants With Potentially Clinically Significant Abnormal Electrocardiogram Findings During the Double-Blind Treatment Period
Data represents the number of participants with potentially clinically significant (PCS) electrocardiogram findings on the final study visit.
Time frame: Final study visit (week 12 or end of treatment visit)
Population: Full analysis set
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo (Double-blind Treatment Period) | Participants With Potentially Clinically Significant Abnormal Electrocardiogram Findings During the Double-Blind Treatment Period | 2 Participants |
| Hydrocodone ER (Double-blind Treatment Period) | Participants With Potentially Clinically Significant Abnormal Electrocardiogram Findings During the Double-Blind Treatment Period | 2 Participants |
Secondary
Participants With Potentially Clinically Significant Abnormal Laboratory Values During the Double-Blind Treatment Period
Data represents participants with potentially clinically significant abnormal serum chemistry, hematology and urinalysis values. Significance criteria: * Blood urea nitrogen: \>=10.71 mmol/L * Creatinine: \>=177 μmol/L * Uric acid: M\>=625, F\>=506 μmol/L * Alanine aminotransferase (ALT): \>=3\* upper limit of normal (ULN) * Gamma-glutamyl transpeptidase (GGT): \>=3\* upper limit of normal (ULN) * Serum white blood cells: \<=3.0 \* 10\^9/L * Hemoglobin: M\<=115, F\<=95 g/dL * Hematocrit: M\<0.37, F\<0.32 L/L * Eosinophils: \>=10.0 % * Absolute neutrophils: \<=1.0 \* 10\^9/L * Urinalysis: Glucose: \>=2 unit increase from baseline
Time frame: Day 1 up to Week 12 of the Treatment Period
Population: Full analysis set including participants with laboratory assessments. Participants with a postbaseline result for that test are counted in each laboratory tests' label.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo (Double-blind Treatment Period) | Participants With Potentially Clinically Significant Abnormal Laboratory Values During the Double-Blind Treatment Period | ALT | 1 Participants |
| Placebo (Double-blind Treatment Period) | Participants With Potentially Clinically Significant Abnormal Laboratory Values During the Double-Blind Treatment Period | Hemoglobin | 1 Participants |
| Placebo (Double-blind Treatment Period) | Participants With Potentially Clinically Significant Abnormal Laboratory Values During the Double-Blind Treatment Period | Uric acid | 3 Participants |
| Placebo (Double-blind Treatment Period) | Participants With Potentially Clinically Significant Abnormal Laboratory Values During the Double-Blind Treatment Period | Hematocrit | 6 Participants |
| Placebo (Double-blind Treatment Period) | Participants With Potentially Clinically Significant Abnormal Laboratory Values During the Double-Blind Treatment Period | GGT | 6 Participants |
| Placebo (Double-blind Treatment Period) | Participants With Potentially Clinically Significant Abnormal Laboratory Values During the Double-Blind Treatment Period | Eosinophils | 1 Participants |
| Placebo (Double-blind Treatment Period) | Participants With Potentially Clinically Significant Abnormal Laboratory Values During the Double-Blind Treatment Period | Creatinine | 0 Participants |
| Placebo (Double-blind Treatment Period) | Participants With Potentially Clinically Significant Abnormal Laboratory Values During the Double-Blind Treatment Period | Absolute neutrophils | 1 Participants |
| Placebo (Double-blind Treatment Period) | Participants With Potentially Clinically Significant Abnormal Laboratory Values During the Double-Blind Treatment Period | White blood cells | 1 Participants |
| Placebo (Double-blind Treatment Period) | Participants With Potentially Clinically Significant Abnormal Laboratory Values During the Double-Blind Treatment Period | Urine glucose | 2 Participants |
| Placebo (Double-blind Treatment Period) | Participants With Potentially Clinically Significant Abnormal Laboratory Values During the Double-Blind Treatment Period | Blood urea nitrogen | 3 Participants |
| Hydrocodone ER (Double-blind Treatment Period) | Participants With Potentially Clinically Significant Abnormal Laboratory Values During the Double-Blind Treatment Period | Urine glucose | 3 Participants |
| Hydrocodone ER (Double-blind Treatment Period) | Participants With Potentially Clinically Significant Abnormal Laboratory Values During the Double-Blind Treatment Period | Blood urea nitrogen | 1 Participants |
| Hydrocodone ER (Double-blind Treatment Period) | Participants With Potentially Clinically Significant Abnormal Laboratory Values During the Double-Blind Treatment Period | Creatinine | 1 Participants |
| Hydrocodone ER (Double-blind Treatment Period) | Participants With Potentially Clinically Significant Abnormal Laboratory Values During the Double-Blind Treatment Period | Uric acid | 4 Participants |
| Hydrocodone ER (Double-blind Treatment Period) | Participants With Potentially Clinically Significant Abnormal Laboratory Values During the Double-Blind Treatment Period | ALT | 2 Participants |
| Hydrocodone ER (Double-blind Treatment Period) | Participants With Potentially Clinically Significant Abnormal Laboratory Values During the Double-Blind Treatment Period | GGT | 5 Participants |
| Hydrocodone ER (Double-blind Treatment Period) | Participants With Potentially Clinically Significant Abnormal Laboratory Values During the Double-Blind Treatment Period | White blood cells | 0 Participants |
| Hydrocodone ER (Double-blind Treatment Period) | Participants With Potentially Clinically Significant Abnormal Laboratory Values During the Double-Blind Treatment Period | Hemoglobin | 2 Participants |
| Hydrocodone ER (Double-blind Treatment Period) | Participants With Potentially Clinically Significant Abnormal Laboratory Values During the Double-Blind Treatment Period | Hematocrit | 3 Participants |
| Hydrocodone ER (Double-blind Treatment Period) | Participants With Potentially Clinically Significant Abnormal Laboratory Values During the Double-Blind Treatment Period | Eosinophils | 2 Participants |
| Hydrocodone ER (Double-blind Treatment Period) | Participants With Potentially Clinically Significant Abnormal Laboratory Values During the Double-Blind Treatment Period | Absolute neutrophils | 2 Participants |
Secondary
Participants With Potentially Clinically Significant Abnormal Vital Sign Values During the Double-Blind Treatment Period
Data represents participants with potentially clinically significant (PCS) vital sign values. Significance criteria * Pulse - high: \>=120 and increase of \>= 15 beats/minute from baseline * Pulse - low: \<=50 and decrease of \>=15 beats/minute * Systolic blood pressure - high: \>=180 and increase \>=20 mmHg * Systolic blood pressure - low: \<=90 and decrease \>=20 mmHg * Diastolic blood pressure - high: \>=105 and increase of \>=15 mmHg * Diastolic blood pressure - low: \<=50 and decrease of \>=15 mmHg
Time frame: Day 1 to Week 12 of the Treatment Period
Population: Full analysis set
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo (Double-blind Treatment Period) | Participants With Potentially Clinically Significant Abnormal Vital Sign Values During the Double-Blind Treatment Period | Diastolic BP - high | 0 Participants |
| Placebo (Double-blind Treatment Period) | Participants With Potentially Clinically Significant Abnormal Vital Sign Values During the Double-Blind Treatment Period | Diastolic BP - low | 0 Participants |
| Placebo (Double-blind Treatment Period) | Participants With Potentially Clinically Significant Abnormal Vital Sign Values During the Double-Blind Treatment Period | Pulse - high | 2 Participants |
| Placebo (Double-blind Treatment Period) | Participants With Potentially Clinically Significant Abnormal Vital Sign Values During the Double-Blind Treatment Period | Pulse - low | 1 Participants |
| Placebo (Double-blind Treatment Period) | Participants With Potentially Clinically Significant Abnormal Vital Sign Values During the Double-Blind Treatment Period | Systolic BP - high | 1 Participants |
| Placebo (Double-blind Treatment Period) | Participants With Potentially Clinically Significant Abnormal Vital Sign Values During the Double-Blind Treatment Period | Systolic BP - low | 2 Participants |
| Hydrocodone ER (Double-blind Treatment Period) | Participants With Potentially Clinically Significant Abnormal Vital Sign Values During the Double-Blind Treatment Period | Systolic BP - high | 2 Participants |
| Hydrocodone ER (Double-blind Treatment Period) | Participants With Potentially Clinically Significant Abnormal Vital Sign Values During the Double-Blind Treatment Period | Diastolic BP - high | 3 Participants |
| Hydrocodone ER (Double-blind Treatment Period) | Participants With Potentially Clinically Significant Abnormal Vital Sign Values During the Double-Blind Treatment Period | Pulse - low | 1 Participants |
| Hydrocodone ER (Double-blind Treatment Period) | Participants With Potentially Clinically Significant Abnormal Vital Sign Values During the Double-Blind Treatment Period | Diastolic BP - low | 2 Participants |
| Hydrocodone ER (Double-blind Treatment Period) | Participants With Potentially Clinically Significant Abnormal Vital Sign Values During the Double-Blind Treatment Period | Systolic BP - low | 3 Participants |
| Hydrocodone ER (Double-blind Treatment Period) | Participants With Potentially Clinically Significant Abnormal Vital Sign Values During the Double-Blind Treatment Period | Pulse - high | 1 Participants |
Secondary
Percentage of Participants With a 30% or Greater Increase in Weekly Average Pain Intensity (API) From Baseline to Week 12 Visit, and an Average API Score of 5 or Higher at Week 12
The API over the last 24 hours was recorded daily by participants in an electronic diary using an 11-point numerical rating scale (NRS-11), a Likert-type scale in which 0=no pain and 10=the worst pain imaginable. Participants selected the number that best described the average pain intensity over the last 24 hours. Weekly API scores averaged daily scores collected over the previous 7 days for each analysis visit.
Time frame: Days -6 to 0 of Treatment Period (baseline), Week 12
Population: Full analysis set, including participants with observed weekly average API for week 12
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo (Double-blind Treatment Period) | Percentage of Participants With a 30% or Greater Increase in Weekly Average Pain Intensity (API) From Baseline to Week 12 Visit, and an Average API Score of 5 or Higher at Week 12 | API increase >=30% and API >=5 | 18.8 percentage of participants |
| Placebo (Double-blind Treatment Period) | Percentage of Participants With a 30% or Greater Increase in Weekly Average Pain Intensity (API) From Baseline to Week 12 Visit, and an Average API Score of 5 or Higher at Week 12 | API increase >=30% | 36.1 percentage of participants |
| Placebo (Double-blind Treatment Period) | Percentage of Participants With a 30% or Greater Increase in Weekly Average Pain Intensity (API) From Baseline to Week 12 Visit, and an Average API Score of 5 or Higher at Week 12 | API >=5 | 24.1 percentage of participants |
| Hydrocodone ER (Double-blind Treatment Period) | Percentage of Participants With a 30% or Greater Increase in Weekly Average Pain Intensity (API) From Baseline to Week 12 Visit, and an Average API Score of 5 or Higher at Week 12 | API increase >=30% and API >=5 | 12.5 percentage of participants |
| Hydrocodone ER (Double-blind Treatment Period) | Percentage of Participants With a 30% or Greater Increase in Weekly Average Pain Intensity (API) From Baseline to Week 12 Visit, and an Average API Score of 5 or Higher at Week 12 | API increase >=30% | 21.1 percentage of participants |
| Hydrocodone ER (Double-blind Treatment Period) | Percentage of Participants With a 30% or Greater Increase in Weekly Average Pain Intensity (API) From Baseline to Week 12 Visit, and an Average API Score of 5 or Higher at Week 12 | API >=5 | 16.4 percentage of participants |
Comparison: API increase \>=30% and API \>=5p-value: 0.029395% CI: [0.47, 0.96]Regression, Logistic
Secondary
Subjective Opiate Withdrawal Scales (SOWS) Total Scores During the Double-Blind Treatment Period
The results of the SOWS were collected in the e-diary daily during the first 4 weeks of the double blind treatment period and then during clinic visits at week 12 or early termination. The SOWS was a self-administered questionnaire used to measure a participant's signs and symptoms of withdrawal from opiates. The scale contained 16 symptoms (such as my nose is running; I feel restless), the participant rated the intensity on a scale of 0 (not at all) to 4 (extremely) for a total score of 0-64. The daily total score for the first 4 weeks was the largest score observed during the time period preceding that visit. For example, the week 1 score for each participant was the largest total score on any day between baseline and the night before the week 1 visit; the week 4 score for each participant was the largest score observed between the week 2 visit and the night before the week 4 visit.
Time frame: Weeks 1, 2, 4 and Endpoint of the Treatment Period
Population: Full analysis set. Participants contributing to each time point are listed in the time point label.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo (Double-blind Treatment Period) | Subjective Opiate Withdrawal Scales (SOWS) Total Scores During the Double-Blind Treatment Period | Week 1 | 6.9 units on a scale | Standard Deviation 7.03 |
| Placebo (Double-blind Treatment Period) | Subjective Opiate Withdrawal Scales (SOWS) Total Scores During the Double-Blind Treatment Period | Week 2 | 5.1 units on a scale | Standard Deviation 6.1 |
| Placebo (Double-blind Treatment Period) | Subjective Opiate Withdrawal Scales (SOWS) Total Scores During the Double-Blind Treatment Period | Week 4 | 5.0 units on a scale | Standard Deviation 5.52 |
| Placebo (Double-blind Treatment Period) | Subjective Opiate Withdrawal Scales (SOWS) Total Scores During the Double-Blind Treatment Period | Endpoint | 5.7 units on a scale | Standard Deviation 6.7 |
| Hydrocodone ER (Double-blind Treatment Period) | Subjective Opiate Withdrawal Scales (SOWS) Total Scores During the Double-Blind Treatment Period | Endpoint | 6.1 units on a scale | Standard Deviation 7.63 |
| Hydrocodone ER (Double-blind Treatment Period) | Subjective Opiate Withdrawal Scales (SOWS) Total Scores During the Double-Blind Treatment Period | Week 1 | 6.6 units on a scale | Standard Deviation 7.36 |
| Hydrocodone ER (Double-blind Treatment Period) | Subjective Opiate Withdrawal Scales (SOWS) Total Scores During the Double-Blind Treatment Period | Week 4 | 5.5 units on a scale | Standard Deviation 6.58 |
| Hydrocodone ER (Double-blind Treatment Period) | Subjective Opiate Withdrawal Scales (SOWS) Total Scores During the Double-Blind Treatment Period | Week 2 | 5.1 units on a scale | Standard Deviation 6.89 |