ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 7 of 146 for:    Hydrocodone

Study to Evaluate the Efficacy and Safety of Hydrocodone Bitartrate Extended-Release Tablets (CEP-33237) for Relief of Moderate to Severe Pain in Patients With Osteoarthritis or Low Back Pain Who Require Opioid Treatment for an Extended Period of Time

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT01240863
Recruitment Status : Completed
First Posted : November 15, 2010
Results First Posted : June 5, 2017
Last Update Posted : June 5, 2017
Sponsor:
Information provided by (Responsible Party):
Teva Pharmaceutical Industries ( Teva Branded Pharmaceutical Products, R&D Inc. )

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Chronic Pain
Interventions Drug: Hydrocodone ER
Drug: Placebo
Enrollment 391
Recruitment Details A total of 519 patients with osteoarthritis or low back pain were screened for enrollment into the study; of these, 391 patients at 71 centers in the US met entry criteria and were enrolled into the titration period of the study.
Pre-assignment Details Of the 389 patients enrolled and treated during the titration period, 294 (75%) patients identified a successful dose and therefore completed the open-label titration period, and were randomly assigned to receive hydrocodone extended-release (ER) tablets (146 patients) or placebo (148 patients) in the double-blind treatment period.
Arm/Group Title Hydrocodone ER (Open-Label Titration Period) Placebo (Double-blind Treatment Period) Hydrocodone ER (Double-blind Treatment Period)
Hide Arm/Group Description All enrolled participants entered the open label titration period and received hydrocodone extended release (ER) tablets beginning with 15 mg every 12 hours for 3 to 7 days. Dosages were titrated upward until pain was effectively controlled. If an effective dosage between 15 mg - 90 mg twice a day was not identified within 6 week, the participant was withdrawn. Participants were administered placebo tablets twice a day 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. Participants were administered hydrocodone ER 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.
Period Title: Open-label Titration Period
Started 391 0 0
Safety Analysis Set 389 0 0
Completed 294 0 0
Not Completed 97 0 0
Reason Not Completed
Adverse Event             47             0             0
Lack of Efficacy             19             0             0
Withdrawal by Subject             9             0             0
Protocol Violation             7             0             0
Noncompliance to study drug admin             3             0             0
Noncompliance to study procedures             3             0             0
Dropped out prior to dosing             2             0             0
Not specified             7             0             0
Period Title: Double-blind Treatment Period (12 Weeks)
Started 0 148 146
Full Analysis and Safety Analysis Sets 0 147 146
Completed 0 102 94
Not Completed 0 46 52
Reason Not Completed
Adverse Event             0             4             10
Lack of Efficacy             0             17             5
Withdrawal by Subject             0             3             5
Protocol Violation             0             9             14
Noncompliance to study drug admin             0             9             11
Noncompliance to study procedures             0             2             2
Not specified             0             1             5
Physician Decision             0             1             0
Arm/Group Title Placebo (Double-blind Treatment Period) Hydrocodone ER (Double-blind Treatment Period) Total
Hide Arm/Group Description 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. Participants were administered hydrocodone ER 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. Total of all reporting groups
Overall Number of Baseline Participants 148 146 294
Hide Baseline Analysis Population Description
Randomized participants
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 148 participants 146 participants 294 participants
52.7  (12.09) 53.6  (10.38) 53.1  (11.26)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 148 participants 146 participants 294 participants
Female
88
  59.5%
87
  59.6%
175
  59.5%
Male
60
  40.5%
59
  40.4%
119
  40.5%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
White Number Analyzed 148 participants 146 participants 294 participants
105
  70.9%
115
  78.8%
220
  74.8%
Black Number Analyzed 148 participants 146 participants 294 participants
41
  27.7%
28
  19.2%
69
  23.5%
Other Number Analyzed 148 participants 146 participants 294 participants
2
   1.4%
3
   2.1%
5
   1.7%
Asian Number Analyzed 148 participants 146 participants 294 participants
0
   0.0%
0
   0.0%
0
   0.0%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Hispanic or Latino Number Analyzed 148 participants 146 participants 294 participants
3
   2.0%
9
   6.2%
12
   4.1%
Non-Hispanic and non-Latino Number Analyzed 148 participants 146 participants 294 participants
144
  97.3%
137
  93.8%
281
  95.6%
Unknown Number Analyzed 148 participants 146 participants 294 participants
1
   0.7%
0
   0.0%
1
   0.3%
Age group  
Measure Type: Count of Participants
Unit of measure:  Participants
<=65 years Number Analyzed 148 participants 146 participants 294 participants
133
  89.9%
126
  86.3%
259
  88.1%
>65 years Number Analyzed 148 participants 146 participants 294 participants
15
  10.1%
20
  13.7%
35
  11.9%
Body Mass Index  
Mean (Standard Deviation)
Unit of measure:  Kg/m^2
Number Analyzed 148 participants 146 participants 294 participants
32.8  (7.33) 33.0  (8.16) 32.9  (7.74)
Type of Pain  
Measure Type: Count of Participants
Unit of measure:  Participants
Low back pain Number Analyzed 148 participants 146 participants 294 participants
107
  72.3%
104
  71.2%
211
  71.8%
Osteoarthritis Number Analyzed 148 participants 146 participants 294 participants
41
  27.7%
42
  28.8%
83
  28.2%
Duration since Diagnosis  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 148 participants 146 participants 294 participants
12.5  (9.06) 12.1  (9.97) 12.3  (9.51)
Participants on Opioid Therapy  
Measure Type: Count of Participants
Unit of measure:  Participants
On opioid therapy Number Analyzed 148 participants 146 participants 294 participants
103
  69.6%
100
  68.5%
203
  69.0%
Not on opioid therapy Number Analyzed 148 participants 146 participants 294 participants
45
  30.4%
46
  31.5%
91
  31.0%
Duration of Opioid Therapy   [1] 
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 103 participants 100 participants 203 participants
4.1  (4.90) 3.9  (4.76) 4.0  (4.82)
[1]
Measure Analysis Population Description: Includes participants with duration of opioid therapy data available.
1.Primary Outcome
Title Change From Baseline to Week 12 in Weekly Average Pain Intensity (wAPI)
Hide Description

The primary efficacy variable was the change from baseline to week 12 in the wAPI. The API over the previous 24 hours, based on the 11-point Numerical Rating Scale (NRS 11), was collected daily by e-diary. The Week 12 wAPI scores from the previous 7 days were calculated for each study visit and averaged. The baseline wAPI score was calculated by averaging API scores from 3 to 12 days when the successful dose of hydrocodone extended release was confirmed at the end of the open label titration period, before patients were randomly assigned study drug. In the case of missing week-12 data due to early withdrawal from the study, or excessive rescue medication usage, the wAPI for week 12 was imputed.

The Numeric Rating Scale (NRS-11) is an 11–point scale for patient self-reporting of pain on a Likert-type scale in which 0 is no pain and 10 is the worst pain imaginable. Negative change from baseline values indicate lessening in pain intensity.

Time Frame Baseline (end of Open-Label Titration Period), Week 12 of Double-blind Treatment Period
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Full analysis set (FAS). One placebo patient was withdrawn from the study prior to receiving drug in the Double-blind Treatment period and is not included in the FAS. In the case of missing week-12 data due to early withdrawal from the study, or excessive rescue medication usage, the wAPI for week 12 was imputed.
Arm/Group Title Placebo (Double-blind Treatment Period) Hydrocodone ER (Double-blind Treatment Period)
Hide Arm/Group Description:
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.
Participants were administered hydrocodone ER 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.
Overall Number of Participants Analyzed 147 146
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
0.14  (0.169) -0.22  (0.176)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo (Double-blind Treatment Period), Hydrocodone ER (Double-blind Treatment Period)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.134
Comments statistical significance level of 0.05.
Method ANCOVA
Comments Treatment and stratification (opioid naïve/opioid experienced) factors as the fixed effects; screening and baseline APIs as covariates.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.35
Confidence Interval (2-Sided) 95%
-0.11 to 0.82
Estimation Comments placebo - hydrocodone
2.Secondary Outcome
Title Percentage of Participants Withdrawn From the Study During the Double-Blind Treatment Period By Reason
Hide Description Percentage of participants who withdrew from the study during the double-blind treatment period. Withdrawal is due to any cause, including lack of efficacy.
Time Frame Day 1 to Week 12 of the double-blind treatment period
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Full analysis set
Arm/Group Title Placebo (Double-blind Treatment Period) Hydrocodone ER (Double-blind Treatment Period)
Hide Arm/Group Description:
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.
Participants were administered hydrocodone ER 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.
Overall Number of Participants Analyzed 147 146
Measure Type: Number
Unit of Measure: percentage of participants
Total withdrawn from study period 31 36
Lack of efficacy 12 3
Adverse event 3 7
Consent withdrawn 2 3
Lost to follow-up 0 0
Protocol violation 6 10
Noncompliance to study procedures 1 1
Noncompliance to study drug admin 6 8
Other 1 3
3.Secondary Outcome
Title Kaplan-Meier Estimates for Time to Discontinuation From the Study
Hide Description Kaplan-Meier estimates for time to discontinuation from the study (due to any cause) was calculated as the number of days since participants were randomly assigned to study drug treatment, ie, the difference between the date the participants withdrew and the date participants were randomly assigned to study drug treatment. The censoring flag was set to 0 if a participant was withdrawn from study drug treatment early and was set to 1 if the participant completed the 12 week treatment period. Censoring time was calculated as the difference of treatment completion date (ie, date of last study drug administration) and date participant was randomly assigned to study drug treatment.
Time Frame Day 1 to Week 12 of the double-blind treatment period
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Full analysis set
Arm/Group Title Placebo (Double-blind Treatment Period) Hydrocodone ER (Double-blind Treatment Period)
Hide Arm/Group Description:
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.
Participants were administered hydrocodone ER 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.
Overall Number of Participants Analyzed 147 146
Median (Inter-Quartile Range)
Unit of Measure: days
99
(48 to 99)
NA [1] 
(35 to NA)
[1]
not estimable due to low rate of discontinuation
4.Secondary Outcome
Title Participants With a Weekly Average Pain Intensity (wAPI) Increase From Baseline Exceeding 33%
Hide Description

The API over the previous 24 hours, based on the 11-point Numerical Rating Scale (NRS 11), was collected daily by e-diary. The wAPI scores from the previous 7 days were calculated for each study visit and averaged. The baseline wAPI score was calculated by averaging API scores from 3 to 12 days when the successful dose of hydrocodone extended release was confirmed at the end of the open label titration period, before patients were randomly assigned study drug.

The Numeric Rating Scale (NRS-11) is an 11–point scale for patient self-reporting of pain on a Likert-type scale in which 0 is no pain and 10 is the worst pain imaginable.

Time Frame Baseline (end of Open-Label Titration Period), Weeks 1, 2, 4, 8, and 12 of the Double-blind treatment period
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Full analysis set. Participants contributing to each time point are included in the number analyzed.
Arm/Group Title Placebo (Double-blind Treatment Period) Hydrocodone ER (Double-blind Treatment Period)
Hide Arm/Group Description:
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.
Participants were administered hydrocodone ER 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.
Overall Number of Participants Analyzed 147 146
Measure Type: Count of Participants
Unit of Measure: Participants
Week 1 Number Analyzed 147 participants 146 participants
14
   9.5%
13
   8.9%
Week 2 Number Analyzed 140 participants 134 participants
31
  22.1%
15
  11.2%
Week 4 Number Analyzed 128 participants 126 participants
32
  25.0%
17
  13.5%
Week 8 Number Analyzed 111 participants 106 participants
26
  23.4%
9
   8.5%
Week 12 Number Analyzed 98 participants 96 participants
24
  24.5%
11
  11.5%
5.Secondary Outcome
Title Participants With a Weekly Average Pain Intensity (wAPI) Increase From Baseline Exceeding 50%
Hide Description

The API over the previous 24 hours, based on the 11-point Numerical Rating Scale (NRS 11), was collected daily by e-diary. The wAPI scores from the previous 7 days were calculated for each study visit and averaged. The baseline wAPI score was calculated by averaging API scores from 3 to 12 days when the successful dose of hydrocodone extended release was confirmed at the end of the open label titration period, before patients were randomly assigned study drug.

The Numeric Rating Scale (NRS-11) is an 11–point scale for patient self-reporting of pain on a Likert-type scale in which 0 is no pain and 10 is the worst pain imaginable.

Time Frame Baseline (end of Open-Label Titration Period), Weeks 1, 2, 4, 8, and 12 of the Double-blind treatment period
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Full analysis set. Participants contributing to each time point are included in the number analyzed.
Arm/Group Title Placebo (Double-blind Treatment Period) Hydrocodone ER (Double-blind Treatment Period)
Hide Arm/Group Description:
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.
Participants were administered hydrocodone ER 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.
Overall Number of Participants Analyzed 147 146
Measure Type: Count of Participants
Unit of Measure: Participants
Week 1 Number Analyzed 147 participants 146 participants
7
   4.8%
9
   6.2%
Week 2 Number Analyzed 140 participants 134 participants
16
  11.4%
9
   6.7%
Week 4 Number Analyzed 128 participants 126 participants
19
  14.8%
9
   7.1%
Week 8 Number Analyzed 111 participants 106 participants
20
  18.0%
6
   5.7%
Week 12 Number Analyzed 98 participants 96 participants
15
  15.3%
6
   6.3%
6.Secondary Outcome
Title Weekly Average Pain Intensity (wAPI) Scores During the Double-blind Treatment Period
Hide Description

The API over the previous 24 hours, based on the 11-point Numerical Rating Scale (NRS 11), was collected daily by e-diary. The wAPI scores from the previous 7 days were calculated for each study visit and averaged. The baseline wAPI score was calculated by averaging API scores from 3 to 12 days when the successful dose of hydrocodone extended release was confirmed at the end of the open label titration period, before patients were randomly assigned study drug.

The Numeric Rating Scale (NRS-11) is an 11–point scale for patient self-reporting of pain on a Likert-type scale in which 0 is no pain and 10 is the worst pain imaginable.

Time Frame Baseline (end of Open-Label Titration Period), Weeks 1, 2, 4, 8, and 12 of the Double-blind treatment period
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Full analysis set. Participants contributing to each time point are included in the number analyzed.
Arm/Group Title Placebo (Double-blind Treatment Period) Hydrocodone ER (Double-blind Treatment Period)
Hide Arm/Group Description:
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.
Participants were administered hydrocodone ER 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.
Overall Number of Participants Analyzed 147 146
Mean (Standard Deviation)
Unit of Measure: units on a scale
Baseline Number Analyzed 147 participants 146 participants
3.75  (0.903) 3.79  (0.981)
Week 1 Number Analyzed 147 participants 146 participants
3.73  (1.319) 3.67  (1.291)
Week 2 Number Analyzed 140 participants 134 participants
3.89  (1.498) 3.58  (1.433)
Week 4 Number Analyzed 128 participants 126 participants
3.78  (1.702) 3.48  (1.447)
Week 8 Number Analyzed 111 participants 106 participants
3.68  (1.823) 3.16  (1.461)
Week 12 Number Analyzed 98 participants 96 participants
3.61  (1.783) 3.30  (1.638)
7.Secondary Outcome
Title Weekly Average Worst Pain Intensity (WPI) Scores During the Double-blind Treatment Period
Hide Description

The WPI was recorded by the patient in the e-diary daily throughout the study, based on the Numeric Rating Scale (NRS-11). Participants were asked to select the number that best described their WPI over the previous 24 hours. Values were averaged for each week.

The Numeric Rating Scale (NRS-11) is an 11–point scale for patient self-reporting of pain on a Likert-type scale in which 0 is no pain and 10 is the worst pain imaginable.

Time Frame Baseline (end of Open-Label Titration Period), Weeks 1, 2, 4, 8, and 12 of the Double-blind treatment period
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Full analysis set. Participants contributing to each time point are included in the number analyzed.
Arm/Group Title Placebo (Double-blind Treatment Period) Hydrocodone ER (Double-blind Treatment Period)
Hide Arm/Group Description:
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.
Participants were administered hydrocodone ER 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.
Overall Number of Participants Analyzed 147 146
Mean (Standard Deviation)
Unit of Measure: units on a scale
Baseline Number Analyzed 147 participants 146 participants
4.75  (1.369) 4.85  (1.265)
Week 1 Number Analyzed 147 participants 146 participants
4.79  (1.776) 4.79  (1.636)
Week 2 Number Analyzed 140 participants 134 participants
5.02  (1.951) 4.65  (1.781)
Week 4 Number Analyzed 128 participants 126 participants
4.77  (2.099) 4.55  (1.832)
Week 8 Number Analyzed 111 participants 106 participants
4.57  (2.228) 4.18  (1.892)
Week 12 Number Analyzed 98 participants 96 participants
4.57  (2.210) 4.22  (1.873)
8.Secondary Outcome
Title Clinician Assessment of Patient Function (CAPF) at Week 4
Hide Description

Clinicians assessed participants across 5 dimensions:

  • Patients general activities
  • Patients walking ability
  • Patients ability to work/perform activities of daily living
  • Patients relationships with others
  • Patients enjoyment of life

Assessments are rated on a 7-point scale, in which 1 is very much worsened and 7 is very much improved since the start of the study.

Time Frame Week 4 of the Double-blind Treatment Period
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
FAS of participants with assessments at the timeframe
Arm/Group Title Placebo (Double-blind Treatment Period) Hydrocodone ER (Double-blind Treatment Period)
Hide Arm/Group Description:
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.
Participants were administered hydrocodone ER 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.
Overall Number of Participants Analyzed 110 105
Measure Type: Count of Participants
Unit of Measure: Participants
General Activities: Very much worsened
0
   0.0%
0
   0.0%
General Activities: Much worsened
1
   0.9%
1
   1.0%
General Activities: Slightly worsened
8
   7.3%
3
   2.9%
General Activities: Unchanged
31
  28.2%
23
  21.9%
General Activities: Slightly improved
33
  30.0%
38
  36.2%
General Activities: Much improved
31
  28.2%
29
  27.6%
General Activities: Very much improved
6
   5.5%
11
  10.5%
Walking ability: Very much worsened
0
   0.0%
1
   1.0%
Walking ability: Much worsened
0
   0.0%
0
   0.0%
Walking ability: Slightly worsened
8
   7.3%
3
   2.9%
Walking ability: Unchanged
35
  31.8%
27
  25.7%
Walking ability: Slightly improved
36
  32.7%
36
  34.3%
Walking ability: Much improved
26
  23.6%
28
  26.7%
Walking ability: Very much improved
5
   4.5%
10
   9.5%
Daily living: Very much worsened
0
   0.0%
0
   0.0%
Daily living: Much worsened
0
   0.0%
2
   1.9%
Daily living: Slightly worsened
6
   5.5%
3
   2.9%
Daily living: Unchanged
36
  32.7%
24
  22.9%
Daily living: Slightly improved
32
  29.1%
39
  37.1%
Daily living: Much improved
29
  26.4%
29
  27.6%
Daily living: Very much improved
7
   6.4%
8
   7.6%
Relationships: Very much worsened
0
   0.0%
0
   0.0%
Relationships: Much worsened
0
   0.0%
1
   1.0%
Relationships: Slightly worsened
3
   2.7%
1
   1.0%
Relationships: Unchanged
72
  65.5%
60
  57.1%
Relationships: Slightly improved
13
  11.8%
18
  17.1%
Relationships: Much improved
16
  14.5%
18
  17.1%
Relationships: Very much improved
6
   5.5%
7
   6.7%
Enjoyment: Very much worsened
0
   0.0%
1
   1.0%
Enjoyment: Much worsened
0
   0.0%
0
   0.0%
Enjoyment: Slightly worsened
8
   7.3%
2
   1.9%
Enjoyment: Unchanged
48
  43.6%
39
  37.1%
Enjoyment: Slightly improved
26
  23.6%
26
  24.8%
Enjoyment: Much improved
19
  17.3%
28
  26.7%
Enjoyment: Very much improved
9
   8.2%
9
   8.6%
9.Secondary Outcome
Title Clinician Assessment of Patient Function (CAPF) at Week 8
Hide Description

Clinicians assessed participants across 5 dimensions:

  • Patients general activities
  • Patients walking ability
  • Patients ability to work/perform activities of daily living
  • Patients relationships with others
  • Patients enjoyment of life

Assessments are rated on a 7-point scale, in which 1 is very much worsened and 7 is very much improved since the start of the study.

Time Frame Week 8 of the Double-blind Treatment Period
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
FAS of participants with assessments at the timeframe
Arm/Group Title Placebo (Double-blind Treatment Period) Hydrocodone ER (Double-blind Treatment Period)
Hide Arm/Group Description:
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.
Participants were administered hydrocodone ER 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.
Overall Number of Participants Analyzed 98 91
Measure Type: Count of Participants
Unit of Measure: Participants
General Activities: Very much worsened
0
   0.0%
1
   1.1%
General Activities: Much worsened
1
   1.0%
1
   1.1%
General Activities: Slightly worsened
6
   6.1%
2
   2.2%
General Activities: Unchanged
34
  34.7%
23
  25.3%
General Activities: Slightly improved
21
  21.4%
24
  26.4%
General Activities: Much improved
27
  27.6%
32
  35.2%
General Activities: Very much improved
9
   9.2%
8
   8.8%
Walking ability: Very much worsened
0
   0.0%
1
   1.1%
Walking ability: Much worsened
2
   2.0%
1
   1.1%
Walking ability: Slightly worsened
5
   5.1%
1
   1.1%
Walking ability: Unchanged
41
  41.8%
30
  33.0%
Walking ability: Slightly improved
19
  19.4%
26
  28.6%
Walking ability: Much improved
24
  24.5%
26
  28.6%
Walking ability: Very much improved
7
   7.1%
6
   6.6%
Daily living: Very much worsened
0
   0.0%
2
   2.2%
Daily living: Much worsened
1
   1.0%
1
   1.1%
Daily living: Slightly worsened
7
   7.1%
0
   0.0%
Daily living: Unchanged
38
  38.8%
25
  27.5%
Daily living: Slightly improved
22
  22.4%
35
  38.5%
Daily living: Much improved
24
  24.5%
21
  23.1%
Daily living: Very much improved
6
   6.1%
7
   7.7%
Relationships: Very much worsened
0
   0.0%
0
   0.0%
Relationships: Much worsened
0
   0.0%
0
   0.0%
Relationships: Slightly worsened
1
   1.0%
2
   2.2%
Relationships: Unchanged
68
  69.4%
49
  53.8%
Relationships: Slightly improved
12
  12.2%
19
  20.9%
Relationships: Much improved
16
  16.3%
17
  18.7%
Relationships: Very much improved
3
   3.1%
4
   4.4%
Enjoyment: Very much worsened
1
   1.0%
0
   0.0%
Enjoyment: Much worsened
0
   0.0%
0
   0.0%
Enjoyment: Slightly worsened
7
   7.1%
1
   1.1%
Enjoyment: Unchanged
38
  38.8%
38
  41.8%
Enjoyment: Slightly improved
19
  19.4%
20
  22.0%
Enjoyment: Much improved
27
  27.6%
25
  27.5%
Enjoyment: Very much improved
6
   6.1%
7
   7.7%
10.Secondary Outcome
Title Clinician Assessment of Patient Function (CAPF) at Week 12
Hide Description

Clinicians assessed participants across 5 dimensions:

  • Patients general activities
  • Patients walking ability
  • Patients ability to work/perform activities of daily living
  • Patients relationships with others
  • Patients enjoyment of life

Assessments are rated on a 7-point scale, in which 1 is very much worsened and 7 is very much improved since the start of the study.

Time Frame Week 12 of the Double-blind Treatment Period
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
FAS of participants with assessments at the timeframe
Arm/Group Title Placebo (Double-blind Treatment Period) Hydrocodone ER (Double-blind Treatment Period)
Hide Arm/Group Description:
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.
Participants were administered hydrocodone ER 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.
Overall Number of Participants Analyzed 92 86
Measure Type: Count of Participants
Unit of Measure: Participants
General Activities: Very much worsened
0
   0.0%
0
   0.0%
General Activities: Much worsened
0
   0.0%
3
   3.5%
General Activities: Slightly worsened
4
   4.3%
2
   2.3%
General Activities: Unchanged
29
  31.5%
20
  23.3%
General Activities: Slightly improved
29
  31.5%
27
  31.4%
General Activities: Much improved
19
  20.7%
27
  31.4%
General Activities: Very much improved
11
  12.0%
7
   8.1%
Walking ability: Very much worsened
0
   0.0%
1
   1.2%
Walking ability: Much worsened
0
   0.0%
2
   2.3%
Walking ability: Slightly worsened
3
   3.3%
3
   3.5%
Walking ability: Unchanged
38
  41.3%
24
  27.9%
Walking ability: Slightly improved
26
  28.3%
24
  27.9%
Walking ability: Much improved
18
  19.6%
27
  31.4%
Walking ability: Very much improved
7
   7.6%
5
   5.8%
Daily living: Very much worsened
0
   0.0%
0
   0.0%
Daily living: Much worsened
0
   0.0%
3
   3.5%
Daily living: Slightly worsened
6
   6.5%
1
   1.2%
Daily living: Unchanged
30
  32.6%
28
  32.6%
Daily living: Slightly improved
26
  28.3%
22
  25.6%
Daily living: Much improved
20
  21.7%
26
  30.2%
Daily living: Very much improved
10
  10.9%
6
   7.0%
Relationships: Very much worsened
0
   0.0%
0
   0.0%
Relationships: Much worsened
0
   0.0%
0
   0.0%
Relationships: Slightly worsened
1
   1.1%
1
   1.2%
Relationships: Unchanged
59
  64.1%
47
  54.7%
Relationships: Slightly improved
13
  14.1%
18
  20.9%
Relationships: Much improved
15
  16.3%
14
  16.3%
Relationships: Very much improved
4
   4.3%
6
   7.0%
Enjoyment: Very much worsened
0
   0.0%
0
   0.0%
Enjoyment: Much worsened
0
   0.0%
2
   2.3%
Enjoyment: Slightly worsened
5
   5.4%
3
   3.5%
Enjoyment: Unchanged
42
  45.7%
31
  36.0%
Enjoyment: Slightly improved
16
  17.4%
23
  26.7%
Enjoyment: Much improved
21
  22.8%
21
  24.4%
Enjoyment: Very much improved
8
   8.7%
6
   7.0%
11.Secondary Outcome
Title Clinician Assessment of Patient Function (CAPF) at Endpoint
Hide Description

Clinicians assessed participants across 5 dimensions:

  • Patients general activities
  • Patients walking ability
  • Patients ability to work/perform activities of daily living
  • Patients relationships with others
  • Patients enjoyment of life

Assessments are rated on a 7-point scale, in which 1 is very much worsened and 7 is very much improved since the start of the study.

Endpoint values are the last observed postbaseline data.

Time Frame Endpoint of the Double-blind Treatment Period (up to week 12)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
FAS of participants with assessments at the timeframe
Arm/Group Title Placebo (Double-blind Treatment Period) Hydrocodone ER (Double-blind Treatment Period)
Hide Arm/Group Description:
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.
Participants were administered hydrocodone ER 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.
Overall Number of Participants Analyzed 131 132
Measure Type: Count of Participants
Unit of Measure: Participants
General Activities: Very much worsened
1
   0.8%
0
   0.0%
General Activities: Much worsened
4
   3.1%
5
   3.8%
General Activities: Slightly worsened
9
   6.9%
4
   3.0%
General Activities: Unchanged
46
  35.1%
38
  28.8%
General Activities: Slightly improved
36
  27.5%
37
  28.0%
General Activities: Much improved
24
  18.3%
40
  30.3%
General Activities: Very much improved
11
   8.4%
8
   6.1%
Walking ability: Very much worsened
1
   0.8%
1
   0.8%
Walking ability: Much worsened
2
   1.5%
4
   3.0%
Walking ability: Slightly worsened
7
   5.3%
5
   3.8%
Walking ability: Unchanged
59
  45.0%
45
  34.1%
Walking ability: Slightly improved
34
  26.0%
32
  24.2%
Walking ability: Much improved
21
  16.0%
19
  14.4%
Walking ability: Very much improved
7
   5.3%
6
   4.5%
Daily living: Very much worsened
1
   0.8%
0
   0.0%
Daily living: Much worsened
4
   3.1%
6
   4.5%
Daily living: Slightly worsened
10
   7.6%
3
   2.3%
Daily living: Unchanged
49
  37.4%
46
  34.8%
Daily living: Slightly improved
33
  25.2%
33
  25.0%
Daily living: Much improved
24
  18.3%
36
  27.3%
Daily living: Very much improved
10
   7.6%
8
   6.1%
Relationships: Very much worsened
0
   0.0%
0
   0.0%
Relationships: Much worsened
1
   0.8%
2
   1.5%
Relationships: Slightly worsened
3
   2.3%
4
   3.0%
Relationships: Unchanged
90
  68.7%
78
  59.1%
Relationships: Slightly improved
15
  11.5%
26
  19.7%
Relationships: Much improved
18
  13.7%
15
  11.4%
Relationships: Very much improved
4
   3.1%
7
   5.3%
Enjoyment: Very much worsened
1
   0.8%
0
   0.0%
Enjoyment: Much worsened
2
   1.5%
5
   3.8%
Enjoyment: Slightly worsened
9
   6.9%
5
   3.8%
Enjoyment: Unchanged
66
  50.4%
57
  43.2%
Enjoyment: Slightly improved
20
  15.3%
31
  23.5%
Enjoyment: Much improved
25
  19.1%
27
  20.5%
Enjoyment: Very much improved
8
   6.1%
7
   5.3%
12.Secondary Outcome
Title Patient Assessment of Function (PAF) at Week 4
Hide Description

The PAF is a self-administered questionnaire used to measure patients’ assessment of their own ability to function in normal activities. Answers to the 7 questions were rated on a 7 point scale in which 1 was very much worsened and 7 were very much improved since the start of the study.

The seven functional areas are:

  • ability to go to work
  • ability to perform at work (includes both work outside the home and housework)
  • ability to walk
  • ability to exercise
  • ability to participate in social events
  • ability to have sex
  • ability to enjoy life
Time Frame Week 4 of the Double-blind Treatment Period
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Full analysis set. Participants contributing to each time point are included in the number analyzed.
Arm/Group Title Placebo (Double-blind Treatment Period) Hydrocodone ER (Double-blind Treatment Period)
Hide Arm/Group Description:
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.
Participants were administered hydrocodone ER 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.
Overall Number of Participants Analyzed 147 146
Measure Type: Count of Participants
Unit of Measure: Participants
Go to Work: Very much worsened Number Analyzed 75 participants 73 participants
0
   0.0%
1
   1.4%
Go to Work: Much worsened Number Analyzed 75 participants 73 participants
2
   2.7%
2
   2.7%
Go to Work: Slightly worsened Number Analyzed 75 participants 73 participants
8
  10.7%
1
   1.4%
Go to Work: Unchanged Number Analyzed 75 participants 73 participants
34
  45.3%
25
  34.2%
Go to Work: Slightly improved Number Analyzed 75 participants 73 participants
13
  17.3%
17
  23.3%
Go to Work: Much improved Number Analyzed 75 participants 73 participants
12
  16.0%
19
  26.0%
Go to Work: Very much improved Number Analyzed 75 participants 73 participants
6
   8.0%
8
  11.0%
Perform Work: Very much worsened Number Analyzed 108 participants 103 participants
0
   0.0%
1
   1.0%
Perform Work: Much worsened Number Analyzed 108 participants 103 participants
3
   2.8%
4
   3.9%
Perform Work: Slightly worsened Number Analyzed 108 participants 103 participants
11
  10.2%
0
   0.0%
Perform Work: Unchanged Number Analyzed 108 participants 103 participants
33
  30.6%
20
  19.4%
Perform Work: Slightly improved Number Analyzed 108 participants 103 participants
32
  29.6%
38
  36.9%
Perform Work: Much improved Number Analyzed 108 participants 103 participants
22
  20.4%
31
  30.1%
Perform Work: Very much improved Number Analyzed 108 participants 103 participants
7
   6.5%
9
   8.7%
Walk: Very much worsened Number Analyzed 109 participants 104 participants
0
   0.0%
0
   0.0%
Walk: Much worsened Number Analyzed 109 participants 104 participants
0
   0.0%
1
   1.0%
Walk: Slightly worsened Number Analyzed 109 participants 104 participants
7
   6.4%
5
   4.8%
Walk: Unchanged Number Analyzed 109 participants 104 participants
37
  33.9%
24
  23.1%
Walk: Slightly improved Number Analyzed 109 participants 104 participants
32
  29.4%
34
  32.7%
Walk: Much improved Number Analyzed 109 participants 104 participants
27
  24.8%
30
  28.8%
Walk: Very much improved Number Analyzed 109 participants 104 participants
6
   5.5%
10
   9.6%
Exercise: Very much worsened Number Analyzed 109 participants 104 participants
1
   0.9%
2
   1.9%
Exercise: Much worsened Number Analyzed 109 participants 104 participants
4
   3.7%
2
   1.9%
Exercise: Slightly worsened Number Analyzed 109 participants 104 participants
6
   5.5%
2
   1.9%
Exercise: Unchanged Number Analyzed 109 participants 104 participants
46
  42.2%
31
  29.8%
Exercise: Slightly improved Number Analyzed 109 participants 104 participants
30
  27.5%
39
  37.5%
Exercise: Much improved Number Analyzed 109 participants 104 participants
18
  16.5%
20
  19.2%
Exercise: Very much improved Number Analyzed 109 participants 104 participants
4
   3.7%
8
   7.7%
Social events: Very much worsened Number Analyzed 109 participants 104 participants
1
   0.9%
0
   0.0%
Social events: Much worsened Number Analyzed 109 participants 104 participants
0
   0.0%
1
   1.0%
Social events: Slightly worsened Number Analyzed 109 participants 104 participants
8
   7.3%
3
   2.9%
Social events: Unchanged Number Analyzed 109 participants 104 participants
52
  47.7%
37
  35.6%
Social events: Slightly improved Number Analyzed 109 participants 104 participants
26
  23.9%
28
  26.9%
Social events: Much improved Number Analyzed 109 participants 104 participants
14
  12.8%
22
  21.2%
Social events: Very much improved Number Analyzed 109 participants 104 participants
8
   7.3%
13
  12.5%
Sex: Very much worsened Number Analyzed 107 participants 101 participants
1
   0.9%
2
   2.0%
Sex: Much worsened Number Analyzed 107 participants 101 participants
5
   4.7%
2
   2.0%
Sex: Slightly worsened Number Analyzed 107 participants 101 participants
8
   7.5%
4
   4.0%
Sex: Unchanged Number Analyzed 107 participants 101 participants
66
  61.7%
64
  63.4%
Sex: Slightly improved Number Analyzed 107 participants 101 participants
18
  16.8%
7
   6.9%
Sex: Much improved Number Analyzed 107 participants 101 participants
5
   4.7%
15
  14.9%
Sex: Very much improved Number Analyzed 107 participants 101 participants
4
   3.7%
7
   6.9%
Enjoy life: Very much worsened Number Analyzed 109 participants 104 participants
1
   0.9%
0
   0.0%
Enjoy life: Much worsened Number Analyzed 109 participants 104 participants
0
   0.0%
2
   1.9%
Enjoy life: Slightly worsened Number Analyzed 109 participants 104 participants
8
   7.3%
4
   3.8%
Enjoy life: Unchanged Number Analyzed 109 participants 104 participants
41
  37.6%
34
  32.7%
Enjoy life: Slightly improved Number Analyzed 109 participants 104 participants
28
  25.7%
27
  26.0%
Enjoy life: Much improved Number Analyzed 109 participants 104 participants
20
  18.3%
28
  26.9%
Enjoy life: Very much improved Number Analyzed 109 participants 104 participants
11
  10.1%
9
   8.7%
13.Secondary Outcome
Title Patient Assessment of Function (PAF) at Week 8
Hide Description

The PAF is a self-administered questionnaire used to measure patients’ assessment of their own ability to function in normal activities. Answers to the 7 questions were rated on a 7 point scale in which 1 was very much worsened and 7 were very much improved since the start of the study.

The seven functional areas are:

  • ability to go to work
  • ability to perform at work (includes both work outside the home and housework)
  • ability to walk
  • ability to exercise
  • ability to participate in social events
  • ability to have sex
  • ability to enjoy life
Time Frame Week 8 of the Double-blind Treatment Period
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Full analysis set. Participants contributing to each time point are included in the number analyzed.
Arm/Group Title Placebo (Double-blind Treatment Period) Hydrocodone ER (Double-blind Treatment Period)
Hide Arm/Group Description:
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.
Participants were administered hydrocodone ER 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.
Overall Number of Participants Analyzed 147 146
Measure Type: Count of Participants
Unit of Measure: Participants
Go to Work: Very much worsened Number Analyzed 65 participants 64 participants
0
   0.0%
2
   3.1%
Go to Work: Much worsened Number Analyzed 65 participants 64 participants
0
   0.0%
0
   0.0%
Go to Work: Slightly worsened Number Analyzed 65 participants 64 participants
7
  10.8%
3
   4.7%
Go to Work: Unchanged Number Analyzed 65 participants 64 participants
31
  47.7%
29
  45.3%
Go to Work: Slightly improved Number Analyzed 65 participants 64 participants
10
  15.4%
9
  14.1%
Go to Work: Much improved Number Analyzed 65 participants 64 participants
14
  21.5%
18
  28.1%
Go to Work: Very much improved Number Analyzed 65 participants 64 participants
3
   4.6%
3
   4.7%
Perform Work: Very much worsened Number Analyzed 97 participants 93 participants
1
   1.0%
2
   2.2%
Perform Work: Much worsened Number Analyzed 97 participants 93 participants
3
   3.1%
0
   0.0%
Perform Work: Slightly worsened Number Analyzed 97 participants 93 participants
7
   7.2%
6
   6.5%
Perform Work: Unchanged Number Analyzed 97 participants 93 participants
38
  39.2%
22
  23.7%
Perform Work: Slightly improved Number Analyzed 97 participants 93 participants
22
  22.7%
25
  26.9%
Perform Work: Much improved Number Analyzed 97 participants 93 participants
17
  17.5%
33
  35.5%
Perform Work: Very much improved Number Analyzed 97 participants 93 participants
9
   9.3%
5
   5.4%
Walk: Very much worsened Number Analyzed 98 participants 93 participants
0
   0.0%
1
   1.1%
Walk: Much worsened Number Analyzed 98 participants 93 participants
2
   2.0%
2
   2.2%
Walk: Slightly worsened Number Analyzed 98 participants 93 participants
7
   7.1%
4
   4.3%
Walk: Unchanged Number Analyzed 98 participants 93 participants
40
  40.8%
22
  23.7%
Walk: Slightly improved Number Analyzed 98 participants 93 participants
23
  23.5%
27
  29.0%
Walk: Much improved Number Analyzed 98 participants 93 participants
17
  17.3%
27
  29.0%
Walk: Very much improved Number Analyzed 98 participants 93 participants
9
   9.2%
10
  10.8%
Exercise: Very much worsened Number Analyzed 98 participants 93 participants
0
   0.0%
2
   2.2%
Exercise: Much worsened Number Analyzed 98 participants 93 participants
3
   3.1%
1
   1.1%
Exercise: Slightly worsened Number Analyzed 98 participants 93 participants
8
   8.2%
8
   8.6%
Exercise: Unchanged Number Analyzed 98 participants 93 participants
42
  42.9%
28
  30.1%
Exercise: Slightly improved Number Analyzed 98 participants 93 participants
23
  23.5%
28
  30.1%
Exercise: Much improved Number Analyzed 98 participants 93 participants
16
  16.3%
21
  22.6%
Exercise: Very much improved Number Analyzed 98 participants 93 participants
6
   6.1%
5
   5.4%
Social events: Very much worsened Number Analyzed 98 participants 93 participants
1
   1.0%
0
   0.0%
Social events: Much worsened Number Analyzed 98 participants 93 participants
1
   1.0%
2
   2.2%
Social events: Slightly worsened Number Analyzed 98 participants 93 participants
3
   3.1%
2
   2.2%
Social events: Unchanged Number Analyzed 98 participants 93 participants
48
  49.0%
42
  45.2%
Social events: Slightly improved Number Analyzed 98 participants 93 participants
18
  18.4%
19
  20.4%
Social events: Much improved Number Analyzed 98 participants 93 participants
18
  18.4%
19
  20.4%
Social events: Very much improved Number Analyzed 98 participants 93 participants
9
   9.2%
9
   9.7%
Sex: Very much worsened Number Analyzed 95 participants 91 participants
0
   0.0%
1
   1.1%
Sex: Much worsened Number Analyzed 95 participants 91 participants
1
   1.1%
0
   0.0%
Sex: Slightly worsened Number Analyzed 95 participants 91 participants
3
   3.2%
9
   9.9%
Sex: Unchanged Number Analyzed 95 participants 91 participants
74
  77.9%
52
  57.1%
Sex: Slightly improved Number Analyzed 95 participants 91 participants
9
   9.5%
12
  13.2%
Sex: Much improved Number Analyzed 95 participants 91 participants
4
   4.2%
14
  15.4%
Sex: Very much improved Number Analyzed 95 participants 91 participants
4
   4.2%
3
   3.3%
Enjoy life: Very much worsened Number Analyzed 98 participants 93 participants
1
   1.0%
0
   0.0%
Enjoy life: Much worsened Number Analyzed 98 participants 93 participants
1
   1.0%
1
   1.1%
Enjoy life: Slightly worsened Number Analyzed 98 participants 93 participants
6
   6.1%
3
   3.2%
Enjoy life: Unchanged Number Analyzed 98 participants 93 participants
41
  41.8%
34
  36.6%
Enjoy life: Slightly improved Number Analyzed 98 participants 93 participants
24
  24.5%
25
  26.9%
Enjoy life: Much improved Number Analyzed 98 participants 93 participants
23
  23.5%
23
  24.7%
Enjoy life: Very much improved Number Analyzed 98 participants 93 participants
3
   3.1%
7
   7.5%
14.Secondary Outcome
Title Patient Assessment of Function (PAF) at Week 12
Hide Description

The PAF is a self-administered questionnaire used to measure patients’ assessment of their own ability to function in normal activities. Answers to the 7 questions were rated on a 7 point scale in which 1 was very much worsened and 7 were very much improved since the start of the study.

The seven functional areas are:

  • ability to go to work
  • ability to perform at work (includes both work outside the home and housework)
  • ability to walk
  • ability to exercise
  • ability to participate in social events
  • ability to have sex
  • ability to enjoy life
Time Frame Week 12 of the Double-blind Treatment Period
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Full analysis set. Participants contributing to each time point are included in the number analyzed.
Arm/Group Title Placebo (Double-blind Treatment Period) Hydrocodone ER (Double-blind Treatment Period)
Hide Arm/Group Description:
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.
Participants were administered hydrocodone ER 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.
Overall Number of Participants Analyzed 147 146
Measure Type: Count of Participants
Unit of Measure: Participants
Go to Work: Very much worsened Number Analyzed 60 participants 61 participants
0
   0.0%
1
   1.6%
Go to Work: Much worsened Number Analyzed 60 participants 61 participants
2
   3.3%
1
   1.6%
Go to Work: Slightly worsened Number Analyzed 60 participants 61 participants
5
   8.3%
3
   4.9%
Go to Work: Unchanged Number Analyzed 60 participants 61 participants
27
  45.0%
19
  31.1%
Go to Work: Slightly improved Number Analyzed 60 participants 61 participants
7
  11.7%
18
  29.5%
Go to Work: Much improved Number Analyzed 60 participants 61 participants
13
  21.7%
17
  27.9%
Go to Work: Very much improved Number Analyzed 60 participants 61 participants
6
  10.0%
2
   3.3%
Perform Work: Very much worsened Number Analyzed 91 participants 84 participants
1
   1.1%
1
   1.2%
Perform Work: Much worsened Number Analyzed 91 participants 84 participants
0
   0.0%
3
   3.6%
Perform Work: Slightly worsened Number Analyzed 91 participants 84 participants
10
  11.0%
5
   6.0%
Perform Work: Unchanged Number Analyzed 91 participants 84 participants
26
  28.6%
20
  23.8%
Perform Work: Slightly improved Number Analyzed 91 participants 84 participants
26
  28.6%
26
  31.0%
Perform Work: Much improved Number Analyzed 91 participants 84 participants
21
  23.1%
25
  29.8%
Perform Work: Very much improved Number Analyzed 91 participants 84 participants
7
   7.7%
4
   4.8%
Walk: Very much worsened Number Analyzed 91 participants 85 participants
1
   1.1%
1
   1.2%
Walk: Much worsened Number Analyzed 91 participants 85 participants
2
   2.2%
2
   2.4%
Walk: Slightly worsened Number Analyzed 91 participants 85 participants
10
  11.0%
5
   5.9%
Walk: Unchanged Number Analyzed 91 participants 85 participants
29
  31.9%
20
  23.5%
Walk: Slightly improved Number Analyzed 91 participants 85 participants
20
  22.0%
27
  31.8%
Walk: Much improved Number Analyzed 91 participants 85 participants
23
  25.3%
23
  27.1%
Walk: Very much improved Number Analyzed 91 participants 85 participants
6
   6.6%
7
   8.2%
Exercise: Very much worsened Number Analyzed 91 participants 85 participants
2
   2.2%
1
   1.2%
Exercise: Much worsened Number Analyzed 91 participants 85 participants
2
   2.2%
3
   3.5%
Exercise: Slightly worsened Number Analyzed 91 participants 85 participants
9
   9.9%
4
   4.7%
Exercise: Unchanged Number Analyzed 91 participants 85 participants
34
  37.4%
30
  35.3%
Exercise: Slightly improved Number Analyzed 91 participants 85 participants
23
  25.3%
26
  30.6%
Exercise: Much improved Number Analyzed 91 participants 85 participants
15
  16.5%
14
  16.5%
Exercise: Very much improved Number Analyzed 91 participants 85 participants
6
   6.6%
7
   8.2%
Social events: Very much worsened Number Analyzed 91 participants 85 participants
1
   1.1%
0
   0.0%
Social events: Much worsened Number Analyzed 91 participants 85 participants
0
   0.0%
2
   2.4%
Social events: Slightly worsened Number Analyzed 91 participants 85 participants
7
   7.7%
6
   7.1%
Social events: Unchanged Number Analyzed 91 participants 85 participants
45
  49.5%
29
  34.1%
Social events: Slightly improved Number Analyzed 91 participants 85 participants
16
  17.6%
25
  29.4%
Social events: Much improved Number Analyzed 91 participants 85 participants
17
  18.7%
16
  18.8%
Social events: Very much improved Number Analyzed 91 participants 85 participants
5
   5.5%
7
   8.2%
Sex: Very much worsened Number Analyzed 91 participants 82 participants
2
   2.2%
0
   0.0%
Sex: Much worsened Number Analyzed 91 participants 82 participants
2
   2.2%
4
   4.9%
Sex: Slightly worsened Number Analyzed 91 participants 82 participants
7
   7.7%
7
   8.5%
Sex: Unchanged Number Analyzed 91 participants 82 participants
64
  70.3%
46
  56.1%
Sex: Slightly improved Number Analyzed 91 participants 82 participants
7
   7.7%
11
  13.4%
Sex: Much improved Number Analyzed 91 participants 82 participants
6
   6.6%
12
  14.6%
Sex: Very much improved Number Analyzed 91 participants 82 participants
3
   3.3%
2
   2.4%
Enjoy life: Very much worsened Number Analyzed 91 participants 85 participants
1
   1.1%
0
   0.0%
Enjoy life: Much worsened Number Analyzed 91 participants 85 participants
0
   0.0%
4
   4.7%
Enjoy life: Slightly worsened Number Analyzed 91 participants 85 participants
7
   7.7%
4
   4.7%
Enjoy life: Unchanged Number Analyzed 91 participants 85 participants
36
  39.6%
27
  31.8%
Enjoy life: Slightly improved Number Analyzed 91 participants 85 participants
21
  23.1%
18
  21.2%
Enjoy life: Much improved Number Analyzed 91 participants 85 participants
18
  19.8%
24
  28.2%
Enjoy life: Very much improved Number Analyzed 91 participants 85 participants
8
   8.8%
8
   9.4%
15.Secondary Outcome
Title Patient Assessment of Function (PAF) at Endpoint
Hide Description

The PAF is a self-administered questionnaire used to measure patients’ assessment of their own ability to function in normal activities. Answers to the 7 questions were rated on a 7 point scale in which 1 was very much worsened and 7 were very much improved since the start of the study.

The seven functional areas are:

  • ability to go to work
  • ability to perform at work (includes both work outside the home and housework)
  • ability to walk
  • ability to exercise
  • ability to participate in social events
  • ability to have sex
  • ability to enjoy life

Endpoint values are the last observed postbaseline data.

Time Frame Endpoint of the Double-blind Treatment Period (up to week 12)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Full analysis set. Participants contributing to each time point are included in the number analyzed.
Arm/Group Title Placebo (Double-blind Treatment Period) Hydrocodone ER (Double-blind Treatment Period)
Hide Arm/Group Description:
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.
Participants were administered hydrocodone ER 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.
Overall Number of Participants Analyzed 147 146
Measure Type: Count of Participants
Unit of Measure: Participants
Go to Work: Very much worsened Number Analyzed 99 participants 106 participants
0
   0.0%
1
   0.9%
Go to Work: Much worsened Number Analyzed 99 participants 106 participants
4
   4.0%
2
   1.9%
Go to Work: Slightly worsened Number Analyzed 99 participants 106 participants
10
  10.1%
6
   5.7%
Go to Work: Unchanged Number Analyzed 99 participants 106 participants
47
  47.5%
39
  36.8%
Go to Work: Slightly improved Number Analyzed 99 participants 106 participants
11
  11.1%
26
  24.5%
Go to Work: Much improved Number Analyzed 99 participants 106 participants
21
  21.2%
26
  24.5%
Go to Work: Very much improved Number Analyzed 99 participants 106 participants
6
   6.1%
6
   5.7%
Perform Work: Very much worsened Number Analyzed 131 participants 133 participants
2
   1.5%
2
   1.5%
Perform Work: Much worsened Number Analyzed 131 participants 133 participants
3
   2.3%
5
   3.8%
Perform Work: Slightly worsened Number Analyzed 131 participants 133 participants
17
  13.0%
12
   9.0%
Perform Work: Unchanged Number Analyzed 131 participants 133 participants
43
  32.8%
34
  25.6%
Perform Work: Slightly improved Number Analyzed 131 participants 133 participants
31
  23.7%
39
  29.3%
Perform Work: Much improved Number Analyzed 131 participants 133 participants
27
  20.6%
34
  25.6%
Perform Work: Very much improved Number Analyzed 131 participants 133 participants
8
   6.1%
7
   5.3%
Walk: Very much worsened Number Analyzed 131 participants 133 participants
1
   0.8%
1
   0.8%
Walk: Much worsened Number Analyzed 131 participants 133 participants
7
   5.3%
4
   3.0%
Walk: Slightly worsened Number Analyzed 131 participants 133 participants
13
   9.9%
10
   7.5%
Walk: Unchanged Number Analyzed 131 participants 133 participants
47
  35.9%
36
  27.1%
Walk: Slightly improved Number Analyzed 131 participants 133 participants
28
  21.4%
40
  30.1%
Walk: Much improved Number Analyzed 131 participants 133 participants
28
  21.4%
32
  24.1%
Walk: Very much improved Number Analyzed 131 participants 133 participants
7
   5.3%
10
   7.5%
Exercise: Very much worsened Number Analyzed 131 participants 133 participants
4
   3.1%
3
   2.3%
Exercise: Much worsened Number Analyzed 131 participants 133 participants
6
   4.6%
5
   3.8%
Exercise: Slightly worsened Number Analyzed 131 participants 133 participants
13
   9.9%
9
   6.8%
Exercise: Unchanged Number Analyzed 131 participants 133 participants
52
  39.7%
51
  38.3%
Exercise: Slightly improved Number Analyzed 131 participants 133 participants
30
  22.9%
30
  22.6%
Exercise: Much improved Number Analyzed 131 participants 133 participants
19
  14.5%
24
  18.0%
Exercise: Very much improved Number Analyzed 131 participants 133 participants
7
   5.3%
9
   6.8%
Social events: Very much worsened Number Analyzed 131 participants 133 participants
1
   0.8%
1
   0.8%
Social events: Much worsened Number Analyzed 131 participants 133 participants
3
   2.3%
4
   3.0%
Social events: Slightly worsened Number Analyzed 131 participants 133 participants
10
   7.6%
12
   9.0%
Social events: Unchanged Number Analyzed 131 participants 133 participants
67
  51.1%
51
  38.3%
Social events: Slightly improved Number Analyzed 131 participants 133 participants
23
  17.6%
30
  22.6%
Social events: Much improved Number Analyzed 131 participants 133 participants
21
  16.0%
25
  18.8%
Social events: Very much improved Number Analyzed 131 participants 133 participants
6
   4.6%
10
   7.5%
Sex: Very much worsened Number Analyzed 131 participants 129 participants
3
   2.3%
0
   0.0%
Sex: Much worsened Number Analyzed 131 participants 129 participants
6
   4.6%
6
   4.7%
Sex: Slightly worsened Number Analyzed 131 participants 129 participants
10
   7.6%
12
   9.3%
Sex: Unchanged Number Analyzed 131 participants 129 participants
88
  67.2%
76
  58.9%
Sex: Slightly improved Number Analyzed 131 participants 129 participants
12
   9.2%
13
  10.1%
Sex: Much improved Number Analyzed 131 participants 129 participants
8
   6.1%
18
  14.0%
Sex: Very much improved Number Analyzed 131 participants 129 participants
4
   3.1%
4
   3.1%
Enjoy life: Very much worsened Number Analyzed 131 participants 132 participants
2
   1.5%
0
   0.0%
Enjoy life: Much worsened Number Analyzed 131 participants 132 participants
3
   2.3%
7
   5.3%
Enjoy life: Slightly worsened Number Analyzed 131 participants 132 participants
10
   7.6%
9
   6.8%
Enjoy life: Unchanged Number Analyzed 131 participants 132 participants
59
  45.0%
45
  34.1%
Enjoy life: Slightly improved Number Analyzed 131 participants 132 participants
27
  20.6%
25
  18.9%
Enjoy life: Much improved Number Analyzed 131 participants 132 participants
21
  16.0%
35
  26.5%
Enjoy life: Very much improved Number Analyzed 131 participants 132 participants
9
   6.9%
11
   8.3%
16.Secondary Outcome
Title Clinician Global Impression of Severity (CGI-S) of Illness Scores During the Double-blind Treatment Period
Hide Description

The CGI-S is a clinician-rated scale that assesses the severity of the patient’s pain condition and response to the treatment. Severity of illness, as related to moderate to severe pain, consists of the following 7 categories:

  • 1 normal–shows no sign of illness,
  • 2 borderline ill,
  • 3 mildly (slightly) ill,
  • 4 moderately ill,
  • 5 markedly ill,
  • 6 severely ill, and
  • 7 among the most extremely ill (Guy 1976).

The clinician assesses the severity of the patient’s condition, based on the clinician’s total clinical experience with patients with this condition, in response to treatment.

Endpoint values are the last observed postbaseline data.

Time Frame Baseline (end of Open-Label Titration Period), Weeks 1, 2, 4, 8, and 12 of the Double-blind treatment period
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Full analysis set. Participants contributing to each time point are included in the number analyzed.
Arm/Group Title Placebo (Double-blind Treatment Period) Hydrocodone ER (Double-blind Treatment Period)
Hide Arm/Group Description:
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.
Participants were administered hydrocodone ER 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.
Overall Number of Participants Analyzed 147 146
Mean (Standard Deviation)
Unit of Measure: units on a scale
Baseline Number Analyzed 147 participants 146 participants
3.0  (1.19) 2.8  (1.07)
Week 1 Number Analyzed 136 participants 132 participants
2.9  (1.16) 2.9  (1.10)
Week 2 Number Analyzed 127 participants 122 participants
2.9  (1.20) 2.8  (1.07)
Week 4 Number Analyzed 110 participants 105 participants
2.9  (1.26) 2.7  (1.03)
Week 8 Number Analyzed 98 participants 93 participants
2.8  (1.21) 2.7  (1.01)
Week 12 Number Analyzed 92 participants 86 participants
2.8  (1.19) 2.7  (1.08)
Endpoint Number Analyzed 146 participants 143 participants
2.9  (1.18) 2.8  (1.12)
17.Secondary Outcome
Title Short-Form Health Survey (SF-36) Physical and Mental Component Summary Scores at Baseline, Week 12 and Endpoint
Hide Description SF-36 is a generic 36-item questionnaire measuring health-related quality of life (HRQL) covering 2 summary measures: physical component summary (PCS) and mental component summary (MCS). The SF-36 consists of 8 subscales. The PCS is represented by 4 subscales: physical function, role limitations due to physical problems, pain, and general health perception. The MCS is represented by 4 subscales: vitality, social function, role limitations due to emotional problems, and mental health. Participants self-report on items in a subscale that have between 2-6 choices per item using Likert-type responses (e.g. none of the time, some of the time, etc.). PCS and MCS scores are constructed as a T-score with a mean of 50 and standard deviation of 10 and no minimum or maximum score; higher scores indicate better health status.
Time Frame Baseline (end of Open-Label Titration Period), Week 12 and Endpoint (last visit up to week 12) of the Double-blind treatment period
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Full analysis set. Participants contributing to each time point are included in the number analyzed.
Arm/Group Title Placebo (Double-blind Treatment Period) Hydrocodone ER (Double-blind Treatment Period)
Hide Arm/Group Description:
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.
Participants were administered hydrocodone ER 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.
Overall Number of Participants Analyzed 147 146
Mean (Standard Deviation)
Unit of Measure: units on a scale
PCS - Baseline Number Analyzed 147 participants 146 participants
35.5  (8.96) 35.8  (9.28)
PCS - Week 12 Number Analyzed 93 participants 84 participants
36.9  (10.04) 37.6  (9.04)
PCS - Endpoint Number Analyzed 120 participants 122 participants
35.9  (10.13) 36.9  (9.16)
MCS - Baseline Number Analyzed 147 participants 146 participants
52.8  (9.99) 52.8  (10.47)
MCS - Week 12 Number Analyzed 93 participants 84 participants
54.7  (9.71) 53.6  (8.06)
MCS - Endpoint Number Analyzed 120 participants 122 participants
54.0  (10.27) 52.6  (9.22)
18.Secondary Outcome
Title Brief Pain Inventory – Short Form (BPI-SF) Pain Interference Mean Score During the Double-Blind Treatment Period
Hide Description For pain interference, the BPI-SF used numerical scales to measure how much pain had interfered with 7 daily activities, including general activity, walking, work, mood, enjoyment of life, relations with others, and sleep in the past 24 hours. The scale used an 11 point Likert scale; range: 0 [does not interfere] to 10 [completely interferes]. BPI pain interference was typically scored as the mean of the 7 interference items. This mean could be used if at least 4 of 7 items had been completed on a given administration.
Time Frame Baseline (end of Open-Label Titration Period), Weeks 1, 2, 4, 8, 12 and Endpoint (last visit up to week 12) of the Double-blind treatment period
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Full analysis set. Participants contributing to each time point are included in the number analyzed.
Arm/Group Title Placebo (Double-blind Treatment Period) Hydrocodone ER (Double-blind Treatment Period)
Hide Arm/Group Description:
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.
Participants were administered ER 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.
Overall Number of Participants Analyzed 147 146
Mean (Standard Deviation)
Unit of Measure: units on a scale
Baseline Number Analyzed 147 participants 146 participants
2.9  (2.09) 2.8  (2.05)
Week 1 Number Analyzed 136 participants 130 participants
3.0  (2.23) 3.1  (2.22)
Week 2 Number Analyzed 130 participants 123 participants
2.9  (2.25) 2.7  (2.19)
Week 4 Number Analyzed 115 participants 111 participants
2.9  (2.39) 2.8  (2.06)
Week 8 Number Analyzed 106 participants 100 participants
2.9  (2.37) 2.9  (2.23)
Week 12 Number Analyzed 102 participants 94 participants
3.0  (2.31) 3.3  (2.30)
Endpoint Number Analyzed 146 participants 144 participants
3.5  (2.45) 3.3  (2.28)
19.Secondary Outcome
Title Participants With Adverse Events
Hide Description 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 up to Day 52 in Open-Label Titration; Day 1 up to Day 128 in Double-Blind Treatment period
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set (Open-Label Titration) and FAS (Double-Blind Treatment)
Arm/Group Title Open-Label Titration: Opioid Naive Open-Label Titration: Opioid Experienced Placebo (Double-blind Treatment Period) Hydrocodone ER (Double-blind Treatment Period)
Hide Arm/Group Description:
During the open label titration period, all participants received hydrocodone extended release tablets on an open-label basis. Opioid naïve participants (ie, those taking less than 10 mg/day of oxycodone or equivalent, during the 14 days before screening) started at a 15 mg dose of hydrocodone extended release, administered every 12 hours. A decision regarding dose adjustment was made based on whether the criterion of successful dose (ie, dose that produced stable pain relief) was met. In general, dose escalation stepped from 15 mg to 30 mg, 45 mg, 60 mg, and 90 mg every 12 hours until stable pain relief was obtained.

During the open label titration period, all participants received hydrocodone extended release tablets on an open-label basis. Opioid experienced participants switched from their current opioid medications to the calculated dose of hydrocodone extended release tablets based on an equianalgesic dose-conversion scheme.

A decision regarding dose adjustment was made based on whether the criterion of successful dose (ie, dose that produced stable pain relief) was met. In general, dose escalation stepped to 30 mg or 45 mg or 60 mg, or 90 mg every 12 hours until stable pain relief was obtained. The escalated dose was dependent upon the initial calculated equivalent dose.

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.
Participants were administered hydrocodone ER 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.
Overall Number of Participants Analyzed 189 200 147 146
Measure Type: Count of Participants
Unit of Measure: Participants
Any adverse event
111
  58.7%
116
  58.0%
91
  61.9%
93
  63.7%
Severe adverse event
9
   4.8%
8
   4.0%
7
   4.8%
9
   6.2%
Treatment-related adverse event
90
  47.6%
72
  36.0%
28
  19.0%
48
  32.9%
Deaths
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Serious adverse event
0
   0.0%
2
   1.0%
3
   2.0%
3
   2.1%
Withdrawals from treatment due to AE
33
  17.5%
15
   7.5%
3
   2.0%
9
   6.2%
20.Secondary Outcome
Title Participants With Potentially Clinically Significant Abnormal Vital Signs Values During the Double-Blind Treatment Period
Hide Description

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 up to Day 128 in Double-Blind Treatment period
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
FAS
Arm/Group Title Placebo (Double-blind Treatment Period) Hydrocodone ER (Double-blind Treatment Period)
Hide Arm/Group Description:
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.
Participants were administered hydrocodone ER 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.
Overall Number of Participants Analyzed 147 146
Measure Type: Count of Participants
Unit of Measure: Participants
At least one clinically significant vital sign
2
   1.4%
5
   3.4%
Pulse - high
0
   0.0%
0
   0.0%
Pulse - low
0
   0.0%
0
   0.0%
Systolic blood pressure - high
1
   0.7%
0
   0.0%
Systolic blood pressure - low
1
   0.7%
3
   2.1%
Diastolic blood pressure - high
0
   0.0%
2
   1.4%
Diastolic blood pressure - low
0
   0.0%
1
   0.7%
21.Secondary Outcome
Title Participants With Potentially Clinically Significant Abnormal Laboratory Values During the Double-Blind Treatment Period
Hide Description

Data represents participants with potentially clinically significant abnormal serum chemistry, hematology and urinalysis values.

Significance criteria:

  • Blood urea nitrogen: >=10.71 mmol/L
  • Uric acid: M>=625, F>=506 μmol/L
  • Hemoglobin: M<=115, F<=95 g/dL
  • Hematocrit: M<0.37, F<0.32 %
  • Urinalysis: blood (hemoglobin) and total protein: >=2 unit increase from baseline
Time Frame Day 1 up to Day 128 in Double-Blind Treatment period
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Full analysis set including participants with laboratory assessments
Arm/Group Title Placebo (Double-blind Treatment Period) Hydrocodone ER (Double-blind Treatment Period)
Hide Arm/Group Description:
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.
Participants were administered hydrocodone ER 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.
Overall Number of Participants Analyzed 147 146
Measure Type: Count of Participants
Unit of Measure: Participants
Blood urea nitrogen Number Analyzed 145 participants 144 participants
1
   0.7%
4
   2.8%
Uric acid Number Analyzed 145 participants 144 participants
2
   1.4%
5
   3.5%
Hemoglobin Number Analyzed 146 participants 143 participants
1
   0.7%
3
   2.1%
Hematocrit Number Analyzed 144 participants 141 participants
1
   0.7%
5
   3.5%
Urine blood Number Analyzed 146 participants 139 participants
2
   1.4%
3
   2.2%
Urine total protein Number Analyzed 146 participants 139 participants
1
   0.7%
0
   0.0%
22.Secondary Outcome
Title Subjective Opiate Withdrawal Scales (SOWS) Scores During the Double-Blind Treatment Period
Hide Description 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 weeks 8 and 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 (eg, 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, 8, 12 and Endpoint (last visit up to Week 12) of the Double-blind treatment period
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Full analysis set. Participants contributing to each time point are included in the number analyzed.
Arm/Group Title Placebo (Double-blind Treatment Period) Hydrocodone ER (Double-blind Treatment Period)
Hide Arm/Group Description:
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.
Participants were administered hydrocodone ER 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.
Overall Number of Participants Analyzed 147 146
Mean (Standard Deviation)
Unit of Measure: units on a scale
Week 1 Number Analyzed 143 participants 142 participants
5.9  (5.39) 6.1  (5.93)
Week 2 Number Analyzed 135 participants 128 participants
5.4  (5.59) 4.4  (5.10)
Week 4 Number Analyzed 130 participants 123 participants
5.5  (6.16) 5.3  (5.37)
Week 8 Number Analyzed 106 participants 99 participants
3.4  (4.68) 3.2  (4.23)
Week 12 Number Analyzed 100 participants 94 participants
3.2  (4.73) 3.6  (5.29)
Endpoint Number Analyzed 147 participants 146 participants
3.6  (4.96) 4.3  (6.30)
23.Secondary Outcome
Title Clinical Opiate Withdrawal Scales (COWS) Scores During the Double-Blind Treatment Period
Hide Description

The COWS was 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 day 0 and weeks 1, 2, 4, 8, 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 Baseline (end of Open-Label Titration Period), Weeks 1, 2, 4, 8, 12 and Endpoint (last visit up to Week 12) of the Double-blind treatment period
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Full analysis set. Participants contributing to each time point are included in the number analyzed.
Arm/Group Title Placebo (Double-blind Treatment Period) Hydrocodone ER (Double-blind Treatment Period)
Hide Arm/Group Description:
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.
Participants were administered hydrocodone ER 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.
Overall Number of Participants Analyzed 147 146
Mean (Standard Deviation)
Unit of Measure: units on a scale
Baseline Number Analyzed 146 participants 146 participants
0.5  (0.90) 0.5  (0.90)
Week 1 Number Analyzed 136 participants 132 participants
0.8  (1.51) 0.7  (1.29)
Week 2 Number Analyzed 130 participants 123 participants
0.7  (1.33) 0.5  (0.92)
Week 4 Number Analyzed 116 participants 111 participants
0.8  (1.58) 0.6  (1.22)
Week 8 Number Analyzed 106 participants 100 participants
0.7  (1.34) 0.6  (1.15)
Week 12 Number Analyzed 101 participants 94 participants
0.5  (0.92) 0.8  (1.76)
Endpoint Number Analyzed 147 participants 146 participants
0.7  (1.13) 1.1  (2.02)
24.Secondary Outcome
Title Addiction Behavior Checklist (ABC) Total Scores During Both the Open-Label Titration and Double-Blind Treatment Periods
Hide Description

The ABC was a clinician rated scale that consisted of a brief (20 item) questionnaire designed to track behaviors characteristic of addiction related to prescription opioid medications in chronic pain populations. Items were focused on observable behaviors noted both during and between clinic visits. Each affirmative response was counted as one point, and points were added to calculate the total score, consequently resulting in scores ranging from 0 to 20 (0=no addiction-related behaviors seen and higher scores indicating an increasing number of addition-related behaviors seen).

The ABC was to be performed at visits 2 and 7 (beginning and end of Open-label Titration period) and weeks 1, 4, 8, and 12 (Double-blind Treatment period) or early termination.

Time Frame Baseline for Open-Label Titration period, Baseline for Double-Blind Treatment period (which is also the end of the Open-Label Titration period), Weeks 1, 4, 8, 12, and Endpoint (last visit up to Week 12) of the Double-blind Treatment period
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Full analysis set. Participants contributing to each time point are included in the number analyzed.
Arm/Group Title Placebo (Double-blind Treatment Period) Hydrocodone ER (Double-blind Treatment Period)
Hide Arm/Group Description:
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.
Participants were administered hydrocodone ER 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.
Overall Number of Participants Analyzed 147 146
Mean (Standard Deviation)
Unit of Measure: units on a scale
Baseline Open-Label Titration Number Analyzed 146 participants 143 participants
0.3  (0.65) 0.3  (0.70)
Baseline Double-blind Treatment Number Analyzed 147 participants 146 participants
0.1  (0.39) 0.2  (0.43)
Week 1 Number Analyzed 136 participants 132 participants
0.2  (0.47) 0.2  (0.50)
Week 4 Number Analyzed 116 participants 111 participants
0.1  (0.40) 0.3  (0.70)
Week 8 Number Analyzed 106 participants 100 participants
0.1  (0.36) 0.2  (0.47)
Week 12 Number Analyzed 102 participants 94 participants
0.1  (0.38) 0.1  (0.38)
Endpoint Number Analyzed 147 participants 146 participants
0.3  (0.75) 0.3  (0.73)
25.Secondary Outcome
Title Current Opioid Misuse Measures (COMM) Total Scores During Both the Open-Label Titration and Double-Blind Treatment Periods
Hide Description

The COMM was a clinician rated scale developed as a brief self report measure of current aberrant drug-related behavior for patients with chronic pain who were already on long term opioid therapy. A total score was calculated as the sum of the 17 questions. The total score ranged from 0 to 68. A score of 0 indicates no aberrant drug-related behaviors were seen. Patients with a total score of 9 or greater were classified as exhibiting aberrant drug-related behavior.

The COMM was to be performed at visits 2 and 7 (beginning and end of Open-label Titration period) and weeks 1, 4, 8, and 12 (Double-blind Treatment period) or early termination.

Time Frame Baseline for Open-Label Titration period, Baseline for Double-Blind Treatment period (which is also the end of the Open-Label Titration period), Weeks 1, 4, 8, 12, and Endpoint (last visit up to Week 12) of the Double-blind Treatment period
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Full analysis set. Participants contributing to each time point are included in the number analyzed.
Arm/Group Title Placebo (Double-blind Treatment Period) Hydrocodone ER (Double-blind Treatment Period)
Hide Arm/Group Description:
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.
Participants were administered hydrocodone ER 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.
Overall Number of Participants Analyzed 147 146
Mean (Standard Deviation)
Unit of Measure: units on a scale
Baseline Open-Label Titration Number Analyzed 146 participants 146 participants
3.7  (4.10) 4.2  (4.14)
Baseline Double-blind Treatment Number Analyzed 147 participants 146 participants
3.7  (4.12) 3.9  (4.29)
Week 1 Number Analyzed 136 participants 131 participants
2.9  (3.70) 3.1  (3.10)
Week 4 Number Analyzed 115 participants 111 participants
2.4  (3.10) 2.8  (3.31)
Week 8 Number Analyzed 106 participants 100 participants
2.5  (3.51) 2.2  (2.87)
Week 12 Number Analyzed 102 participants 93 participants
2.8  (3.51) 3.0  (3.53)
Endpoint Number Analyzed 147 participants 146 participants
3.0  (3.67) 3.3  (3.78)
26.Secondary Outcome
Title Change From Baseline to Endpoint in the Double-Blind Treatment Phase in Electrocardiogram (ECG) Parameters
Hide Description A 12-lead ECG was conducted at baseline and the last visit during the double-blind treatment period (week 12, or early termination).
Time Frame Baseline (end of Open-Label Titration Period), Endpoint (last visit up to Week 12) of the Double-blind treatment period
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
FAS of participants contributing baseline and endpoint data.
Arm/Group Title Placebo (Double-blind Treatment Period) Hydrocodone ER (Double-blind Treatment Period)
Hide Arm/Group Description:
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.
Participants were administered hydrocodone ER 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.
Overall Number of Participants Analyzed 146 142
Mean (Standard Deviation)
Unit of Measure: msec
PR interval -1.8  (16.27) -2.4  (29.30)
QRS interval -0.1  (15.96) 0.6  (10.43)
QT interval -3.1  (27.08) 2.2  (28.28)
QTc interval (Bazett) -1.0  (20.34) 4.2  (22.74)
QTc interval (Fridericia) -2.5  (21.10) 2.9  (21.70)
Time Frame Day 1 up to Day 52 in Open-Label Titration; Day 1 up to Day 128 in Double-Blind Treatment period
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Hydrocodone ER (Open-Label Titration Period) Placebo (Double-blind Treatment Period) Hydrocodone ER (Double-blind Treatment Period)
Hide Arm/Group Description All enrolled participants entered the open label titration period and received hydrocodone extended release (ER) tablets beginning with 15 mg every 12 hours for 3 to 7 days. Dosages were titrated upward until pain was effectively controlled. If an effective dosage between 15 mg - 90 mg twice a day was not identified within 6 week, the participant was withdrawn. Participants were administered placebo tablets twice a day 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. Participants were administered hydrocodone ER 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.
All-Cause Mortality
Hydrocodone ER (Open-Label Titration Period) Placebo (Double-blind Treatment Period) Hydrocodone ER (Double-blind Treatment Period)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Hydrocodone ER (Open-Label Titration Period) Placebo (Double-blind Treatment Period) Hydrocodone ER (Double-blind Treatment Period)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   2/389 (0.51%)      3/147 (2.04%)      3/146 (2.05%)    
Gastrointestinal disorders       
Oesophagitis  1  0/389 (0.00%)  0 0/147 (0.00%)  0 1/146 (0.68%)  1
Pancreatitis  1  0/389 (0.00%)  0 0/147 (0.00%)  0 1/146 (0.68%)  2
General disorders       
Hernia obstructive  1  0/389 (0.00%)  0 0/147 (0.00%)  0 1/146 (0.68%)  1
Immune system disorders       
Anaphylactic reaction  1  0/389 (0.00%)  0 0/147 (0.00%)  0 1/146 (0.68%)  1
Injury, poisoning and procedural complications       
Hip fracture  1  0/389 (0.00%)  0 1/147 (0.68%)  1 0/146 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Basal cell carcinoma  1  0/389 (0.00%)  0 1/147 (0.68%)  2 0/146 (0.00%)  0
Bladder cancer recurrent  1  0/389 (0.00%)  0 1/147 (0.68%)  1 0/146 (0.00%)  0
Renal and urinary disorders       
Renal failure acute  1  1/389 (0.26%)  1 0/147 (0.00%)  0 0/146 (0.00%)  0
Vascular disorders       
Deep vein thrombosis  1  1/389 (0.26%)  1 0/147 (0.00%)  0 0/146 (0.00%)  0
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (13.0)
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Hydrocodone ER (Open-Label Titration Period) Placebo (Double-blind Treatment Period) Hydrocodone ER (Double-blind Treatment Period)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   167/389 (42.93%)      24/147 (16.33%)      45/146 (30.82%)    
Gastrointestinal disorders       
Constipation  1  55/389 (14.14%)  61 7/147 (4.76%)  8 19/146 (13.01%)  19
Nausea  1  70/389 (17.99%)  75 9/147 (6.12%)  11 19/146 (13.01%)  20
Vomiting  1  25/389 (6.43%)  26 5/147 (3.40%)  6 9/146 (6.16%)  9
Nervous system disorders       
Dizziness  1  22/389 (5.66%)  23 1/147 (0.68%)  1 3/146 (2.05%)  3
Headache  1  43/389 (11.05%)  50 8/147 (5.44%)  8 10/146 (6.85%)  13
Somnolence  1  45/389 (11.57%)  51 1/147 (0.68%)  1 3/146 (2.05%)  3
Skin and subcutaneous tissue disorders       
Pruritus  1  20/389 (5.14%)  23 1/147 (0.68%)  1 3/146 (2.05%)  4
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (13.0)
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Sponsor has the right 60 days before submission for publication to review/provide comments. If the Sponsor’s review shows that potentially patentable subject matter would be disclosed, publication or public disclosure shall be delayed for up to 90 additional days in order for the Sponsor, or Sponsor’s designees, to file the necessary patent applications. In multicenter trials, each PI will postpone single center publications until after disclosure or publication of multicenter data.
Results Point of Contact
Name/Title: Director, Clinical Research
Organization: Teva Branded Pharmaceutical Products, R&D Inc
Phone: 215-591-3000
Responsible Party: Teva Pharmaceutical Industries ( Teva Branded Pharmaceutical Products, R&D Inc. )
ClinicalTrials.gov Identifier: NCT01240863     History of Changes
Other Study ID Numbers: C33237/3079
First Submitted: November 10, 2010
First Posted: November 15, 2010
Results First Submitted: February 19, 2017
Results First Posted: June 5, 2017
Last Update Posted: June 5, 2017