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Efficacy and Safety of Oxycodone/Naloxone Controlled-release Tablets (OXN) Compared to Placebo in Opioid-experienced Subjects With Moderate to Severe Chronic Low Back Pain

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ClinicalTrials.gov Identifier: NCT01358526
Recruitment Status : Completed
First Posted : May 23, 2011
Results First Posted : September 3, 2014
Last Update Posted : November 11, 2015
Sponsor:
Information provided by (Responsible Party):
Purdue Pharma LP

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Low Back Pain
Interventions Drug: Oxycodone/Naloxone Controlled-release
Drug: Placebo
Enrollment 1095
Recruitment Details First subject first visit: 25-May-2011; Last subject last visit: 15-Oct-2012. The study was conducted at 132 medical/research sites in the United States.
Pre-assignment Details Opioid-experienced subjects with moderate to severe pain due to chronic low back pain, who required around-the-clock opioid therapy.
Arm/Group Title Open-label Titration OXN OXN Group Placebo Group
Hide Arm/Group Description The open-label titration was designed to identify a stable, effective, and tolerable dose of OXN for each subject.

Oxycodone/Naloxone Controlled-release Tablets (OXN)

Oxycodone/Naloxone Controlled-release: Oxycodone/Naloxone Controlled-release tablets (10/5 mg, 20/10 mg, 30/15 mg, 40/20 mg) taken orally every 12 hours

Placebo tablets to match OXN

Placebo: Placebo tablets to match OXN taken orally every 12 hours

Period Title: Open-label Titration Period
Started 1095 0 0
Completed 601 [1] 0 0
Not Completed 494 0 0
Reason Not Completed
Adverse Event             95             0             0
Withdrawal by Subject             65             0             0
Lost to Follow-up             25             0             0
Lack of Efficacy             107             0             0
Confirmed or suspected diversion             16             0             0
Administrative             8             0             0
Did not qualify             178             0             0
[1]
1 subject was randomized but never received double-blind treatment: Randomized Safety Population=600
Period Title: Double-blind Phase
Started 0 298 [1] 302 [1]
Completed 0 218 181
Not Completed 0 80 121
Reason Not Completed
Adverse Event             0             24             23
Withdrawal by Subject             0             10             8
Lost to Follow-up             0             4             1
Lack of Efficacy             0             31             73
Confirmed or suspected diversion             0             5             6
Administrative             0             6             10
[1]
1 subject was randomized but never received double-blind treatment: Randomized Safety Population=600
Arm/Group Title OXN Group Placebo Group Total
Hide Arm/Group Description

Oxycodone/Naloxone Controlled-release Tablets (OXN)

Oxycodone/Naloxone Controlled-release: Oxycodone/Naloxone Controlled-release tablets (10/5 mg, 20/10 mg, 30/15 mg, 40/20 mg) taken orally every 12 hours

Placebo tablets to match OXN

Placebo: Placebo tablets to match OXN taken orally every 12 hours

Total of all reporting groups
Overall Number of Baseline Participants 298 302 600
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 298 participants 302 participants 600 participants
53.5  (11.69) 53.0  (10.97) 53.2  (11.33)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 298 participants 302 participants 600 participants
Female
162
  54.4%
176
  58.3%
338
  56.3%
Male
136
  45.6%
126
  41.7%
262
  43.7%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 298 participants 302 participants 600 participants
White 229 233 462
Black or African American 53 61 114
Asian 8 3 11
American Indian or Alaska Native 1 3 4
Other 7 2 9
1.Primary Outcome
Title The “Average Pain Over the Last 24 Hours” at Week 12 of the Double-blind Period
Hide Description The “average pain over the last 24 hours” score was collected using an 11-point numerical rating scale ranging from 0 to 10; where 0=no pain and 10=pain as bad as you can imagine.
Time Frame 24 hours (Week 12)
Hide Outcome Measure Data
Hide Analysis Population Description
The full analysis population for efficacy (N = 600) was the group of subjects who were randomized and received at least 1 dose of double-blind study drug
Arm/Group Title OXN Group Placebo Group
Hide Arm/Group Description:

Oxycodone/Naloxone Controlled-release Tablets (OXN)

Oxycodone/Naloxone Controlled-release: Oxycodone/Naloxone Controlled-release tablets (10/5 mg, 20/10 mg, 30/15 mg, 40/20 mg) taken orally every 12 hours

Placebo tablets to match OXN

Placebo: Placebo tablets to match OXN taken orally every 12 hours

Overall Number of Participants Analyzed 298 302
Mean (Standard Error)
Unit of Measure: units on a scale (0 - 10)
3.86  (0.116) 4.32  (0.115)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection OXN Group, Placebo Group
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0055
Comments A gate-keeping strategy and a Bonferroni-Holm method was used to control the family-wise (primary and secondary efficacy analysis) error rate at the 5% level.
Method Mixed Models Analysis
Comments Mixed-model repeated measures analysis of pain data using a pattern mixture model framework
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.45
Confidence Interval (2-Sided) 95%
0.13 to 0.77
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.163
Estimation Comments [Not Specified]
2.Secondary Outcome
Title The Sleep Disturbance Subscale of the MOS Sleep Scale at Weeks 4, 8, and 12
Hide Description The scale consists of 12 individual items (4 sleep disturbance, 2 sleep adequacy, 1 quantity of sleep, 3 somnolence, 1 snoring, 1 shortness of breath). Only Sleep Disturbance Subscale questions 1, 3, 7, and 8 were analyzed; scores range from 0 to 100, where higher scores indicate greater sleep disturbance.
Time Frame Weeks 4, 8, and 12
Hide Outcome Measure Data
Hide Analysis Population Description
The full analysis population for efficacy (N = 600) was the group of subjects who were randomized and received at least 1 dose of double-blind study drug
Arm/Group Title OXN Group Placebo Group
Hide Arm/Group Description:

Oxycodone/Naloxone Controlled-release Tablets (OXN)

Oxycodone/Naloxone Controlled-release: Oxycodone/Naloxone Controlled-release tablets (10/5 mg, 20/10 mg, 30/15 mg, 40/20 mg) taken orally every 12 hours

Placebo tablets to match OXN

Placebo: Placebo tablets to match OXN taken orally every 12 hours

Overall Number of Participants Analyzed 298 302
Mean (95% Confidence Interval)
Unit of Measure: units on a scale
Week 4
32.5
(29.4 to 35.7)
38.0
(34.8 to 41.3)
Week 8
30.8
(27.8 to 33.9)
36.8
(33.6 to 39.9)
Week 12
31.1
(28.1 to 34.2)
36.4
(33.2 to 39.7)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection OXN Group, Placebo Group
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0191
Comments [Not Specified]
Method Mixed Models Analysis
Comments Mixed-model repeated measures analysis
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 5.3
Confidence Interval (2-Sided) 95%
0.9 to 9.8
Parameter Dispersion
Type: Standard Error of the mean
Value: 2.26
Estimation Comments Mean difference (final values) is the treatment comparison estimated using mixed model repeated measures analysis with effect for treatment, time (weeks 4, 8, 12), treatment by time interaction, and prerandomization value. Subject is a random effect.
3.Secondary Outcome
Title Patient Global Impression of Change (PGIC)
Time Frame Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
The full analysis population for efficacy (N = 600) was the group of subjects who were randomized and received at least 1 dose of double-blind study drug
Arm/Group Title OXN Group Placebo Group
Hide Arm/Group Description:

Oxycodone/Naloxone Controlled-release Tablets (OXN)

Oxycodone/Naloxone Controlled-release: Oxycodone/Naloxone Controlled-release tablets (10/5 mg, 20/10 mg, 30/15 mg, 40/20 mg) taken orally every 12 hours

Placebo tablets to match OXN

Placebo: Placebo tablets to match OXN taken orally every 12 hours

Overall Number of Participants Analyzed 298 302
Measure Type: Number
Unit of Measure: participants (responders)
153 109
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection OXN Group, Placebo Group
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0002
Comments The proportion of subjects responding "much improved" and "very much improved" was summarized by treatment group and compared between groups using an exact test
Method Fisher Exact
Comments [Not Specified]
4.Other Pre-specified Outcome
Title Responder Analysis for Subjects With a ≥ 30% Reduction in Pain Compared to Baseline
Hide Description A subject’s response to treatment was defined as the percentage reduction from the screening mean pain score to the “average pain over the last 24 hours” score for week 12 of the double-blind period.
Time Frame Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
The full analysis population for efficacy (N = 600) was the group of subjects who were randomized and received at least 1 dose of double-blind study drug
Arm/Group Title OXN Group Placebo Group
Hide Arm/Group Description:

Oxycodone/Naloxone Controlled-release Tablets (OXN)

Oxycodone/Naloxone Controlled-release: Oxycodone/Naloxone Controlled-release tablets (10/5 mg, 20/10 mg, 30/15 mg, 40/20 mg) taken orally every 12 hours

Placebo tablets to match OXN

Placebo: Placebo tablets to match OXN taken orally every 12 hours

Overall Number of Participants Analyzed 298 302
Measure Type: Number
Unit of Measure: participants (responders)
164 124
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection OXN Group, Placebo Group
Comments Proportion of subjects with a response to treatment that is ≥ 30%
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0006
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments Cochran-Mantel-Haenszel test: responder as dependent variable, treatment as explanatory variable, dose at time of randomization as stratifying factor
5.Other Pre-specified Outcome
Title Responder Analysis for Subjects With a ≥ 50% Reduction in Pain Compared to Baseline
Hide Description A subject’s response to treatment was defined as the percentage reduction from the screening mean pain score to the “average pain over the last 24 hours” score for week 12 of the double-blind period.
Time Frame Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
The full analysis population for efficacy (N = 600) was the group of subjects who were randomized and received at least 1 dose of double-blind study drug
Arm/Group Title OXN Group Placebo Group
Hide Arm/Group Description:

Oxycodone/Naloxone Controlled-release Tablets (OXN)

Oxycodone/Naloxone Controlled-release: Oxycodone/Naloxone Controlled-release tablets (10/5 mg, 20/10 mg, 30/15 mg, 40/20 mg) taken orally every 12 hours

Placebo tablets to match OXN

Placebo: Placebo tablets to match OXN taken orally every 12 hours

Overall Number of Participants Analyzed 298 302
Measure Type: Number
Unit of Measure: participants (responders)
109 75
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection OXN Group, Placebo Group
Comments Proportion of subjects with a response to treatment that is ≥ 50%
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0018
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments Cochran-Mantel-Haenszel test: responder as dependent variable, treatment as explanatory variable, dose at time of randomization as stratifying factor
Time Frame Adverse events (AEs) were reported from start of study participation through the period beyond study completion.
Adverse Event Reporting Description AEs were learned of through spontaneous reports and/or subject interview, or were observed during physical examinations or other safety assessments. Ongoing AEs were followed until resolution or 30 days after last study drug dose. Serious AEs up to 30 days following the last study visit were followed until the AE or sequelae resolved or stabilized.
 
Arm/Group Title Open-label Titration OXN Double-blind Placebo Double-blind OXN
Hide Arm/Group Description

Oxycodone/Naloxone Controlled-release Tablets (OXN)

Oxycodone/Naloxone Controlled-release: Oxycodone/Naloxone Controlled-release tablets (10/5 mg, 20/10 mg, 30/15 mg, 40/20 mg) taken orally every 12 hours

Placebo tablets to match OXN

Placebo: Placebo tablets to match OXN taken orally every 12 hours

Oxycodone/Naloxone Controlled-release Tablets (OXN)

Oxycodone/Naloxone Controlled-release: Oxycodone/Naloxone Controlled-release tablets (10/5 mg, 20/10 mg, 30/15 mg, 40/20 mg) taken orally every 12 hours

All-Cause Mortality
Open-label Titration OXN Double-blind Placebo Double-blind OXN
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Open-label Titration OXN Double-blind Placebo Double-blind OXN
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   11/1095 (1.00%)   12/302 (3.97%)   19/298 (6.38%) 
Cardiac disorders       
Acute myocardial infarction  1  0/1095 (0.00%)  2/302 (0.66%)  0/298 (0.00%) 
Angina pectoris  1  0/1095 (0.00%)  0/302 (0.00%)  1/298 (0.34%) 
Atrial fibrillation  1  0/1095 (0.00%)  0/302 (0.00%)  1/298 (0.34%) 
Gastrointestinal disorders       
Abdominal pain  1  0/1095 (0.00%)  0/302 (0.00%)  1/298 (0.34%) 
Impaired gastric emptying  1  1/1095 (0.09%)  0/302 (0.00%)  0/298 (0.00%) 
Nausea  1  1/1095 (0.09%)  0/302 (0.00%)  0/298 (0.00%) 
Oesophageal stenosis  1  1/1095 (0.09%)  0/302 (0.00%)  0/298 (0.00%) 
Rectal perforation  1  0/1095 (0.00%)  0/302 (0.00%)  1/298 (0.34%) 
Vomiting  1  1/1095 (0.09%)  0/302 (0.00%)  0/298 (0.00%) 
General disorders       
Non-cardiac chest pain  1  0/1095 (0.00%)  0/302 (0.00%)  1/298 (0.34%) 
Hepatobiliary disorders       
Cholecystitis  1  0/1095 (0.00%)  0/302 (0.00%)  1/298 (0.34%) 
Cholecystitis acute  1  0/1095 (0.00%)  1/302 (0.33%)  0/298 (0.00%) 
Cholelithiasis  1  0/1095 (0.00%)  1/302 (0.33%)  0/298 (0.00%) 
Infections and infestations       
Cellulitis  1  0/1095 (0.00%)  0/302 (0.00%)  1/298 (0.34%) 
Gallbladder empyema  1  0/1095 (0.00%)  1/302 (0.33%)  0/298 (0.00%) 
Gangrene  1  0/1095 (0.00%)  1/302 (0.33%)  0/298 (0.00%) 
Ludwig angina  1  0/1095 (0.00%)  0/302 (0.00%)  1/298 (0.34%) 
Pneumonia  1  0/1095 (0.00%)  1/302 (0.33%)  1/298 (0.34%) 
Injury, poisoning and procedural complications       
Gun shot wound  1 [1]  0/1095 (0.00%)  1/302 (0.33%)  0/298 (0.00%) 
Overdose  1  1/1095 (0.09%)  0/302 (0.00%)  0/298 (0.00%) 
Investigations       
Drug screen positive  1  5/1095 (0.46%)  1/302 (0.33%)  9/298 (3.02%) 
Hepatic enzyme increased  1  0/1095 (0.00%)  1/302 (0.33%)  0/298 (0.00%) 
Metabolism and nutrition disorders       
Dehydration  1  1/1095 (0.09%)  0/302 (0.00%)  0/298 (0.00%) 
Hypokalaemia  1  0/1095 (0.00%)  0/302 (0.00%)  1/298 (0.34%) 
Musculoskeletal and connective tissue disorders       
Arthritis  1  1/1095 (0.09%)  0/302 (0.00%)  0/298 (0.00%) 
Systemic lupus erythematosus  1  0/1095 (0.00%)  1/302 (0.33%)  0/298 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Bladder cancer  1  0/1095 (0.00%)  0/302 (0.00%)  1/298 (0.34%) 
Nervous system disorders       
Syncope  1  0/1095 (0.00%)  0/302 (0.00%)  1/298 (0.34%) 
Psychiatric disorders       
Drug abuse  1  3/1095 (0.27%)  0/302 (0.00%)  0/298 (0.00%) 
Renal and urinary disorders       
Renal failure  1  0/1095 (0.00%)  1/302 (0.33%)  0/298 (0.00%) 
Social circumstances       
Substance abuse  1  0/1095 (0.00%)  2/302 (0.66%)  0/298 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (15.0)
[1]
Death
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Open-label Titration OXN Double-blind Placebo Double-blind OXN
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   79/1095 (7.21%)   34/302 (11.26%)   41/298 (13.76%) 
Gastrointestinal disorders       
Nausea  1  79/1095 (7.21%)  14/302 (4.64%)  25/298 (8.39%) 
Investigations       
Drug screen positive  1  23/1095 (2.10%)  20/302 (6.62%)  19/298 (6.38%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (15.0)
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.
Results Point of Contact
Name/Title: Clinical Leader
Organization: Purdue Pharma L.P.
Phone: 800-733-1333
Responsible Party: Purdue Pharma LP
ClinicalTrials.gov Identifier: NCT01358526     History of Changes
Other Study ID Numbers: ONU3701
First Submitted: May 20, 2011
First Posted: May 23, 2011
Results First Submitted: July 29, 2014
Results First Posted: September 3, 2014
Last Update Posted: November 11, 2015