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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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Teva Pharmaceutical Industries ( Teva Branded Pharmaceutical Products, R&D Inc. )
ClinicalTrials.gov Identifier:
NCT01240863
First received: November 10, 2010
Last updated: June 2, 2017
Last verified: June 2017
Results First Received: February 19, 2017  
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

  Participant Flow
  Hide Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
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
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
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.

Reporting Groups
  Description
Hydrocodone ER (Open-Label Titration Period) 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 If an effective dosage between 15 mg - 90 mg twice a day was not identified within 6 week, the participant was withdrawn.
Placebo (Double-blind Treatment Period) 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.
Hydrocodone ER (Double-blind Treatment Period) 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.

Participant Flow for 2 periods

Period 1:   Open-label Titration Period
    Hydrocodone ER (Open-Label Titration Period)   Placebo (Double-blind Treatment Period)   Hydrocodone ER (Double-blind Treatment Period)
STARTED   391   0   0 
Safety Analysis Set   389   0   0 
COMPLETED   294   0   0 
NOT COMPLETED   97   0   0 
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 2:   Double-blind Treatment Period (12 Weeks)
    Hydrocodone ER (Open-Label Titration Period)   Placebo (Double-blind Treatment Period)   Hydrocodone ER (Double-blind Treatment Period)
STARTED   0   148   146 
Full Analysis and Safety Analysis Sets   0   147   146 
COMPLETED   0   102   94 
NOT COMPLETED   0   46   52 
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 



  Baseline Characteristics
  Hide Baseline Characteristics

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Randomized participants

Reporting Groups
  Description
Placebo (Double-blind Treatment Period) Participants were administered placebo tablets every 12 hours that matched the dosage deemed successful for managing their pain during the titration period. A step wise, double-blind tapering schedule was implemented during the first 2 weeks of the 12 week, double blind, placebo controlled treatment period to reduce the risk of withdrawal effects in patients randomly assigned to placebo.
Hydrocodone ER (Double-blind Treatment Period) 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 Total of all reporting groups

Baseline Measures
   Placebo (Double-blind Treatment Period)   Hydrocodone ER (Double-blind Treatment Period)   Total 
Overall Participants Analyzed 
[Units: Participants]
 148   146   294 
Age 
[Units: Years]
Mean (Standard Deviation)
     
Participants Analyzed 
[Units: Participants]
 148   146   294 
   52.7  (12.09)   53.6  (10.38)   53.1  (11.26) 
Sex: Female, Male 
[Units: Participants]
Count of Participants
     
Participants Analyzed 
[Units: Participants]
 148   146   294 
Female      88  59.5%      87  59.6%      175  59.5% 
Male      60  40.5%      59  40.4%      119  40.5% 
Race/Ethnicity, Customized 
[Units: Participants]
Count of Participants
     
White       
Participants Analyzed 
[Units: Participants]
 148   146   294 
White   105   115   220 
Black       
Participants Analyzed 
[Units: Participants]
 148   146   294 
Black   41   28   69 
Other       
Participants Analyzed 
[Units: Participants]
 148   146   294 
Other   2   3   5 
Asian       
Participants Analyzed 
[Units: Participants]
 148   146   294 
Asian   0   0   0 
Race/Ethnicity, Customized 
[Units: Participants]
Count of Participants
     
Hispanic or Latino       
Participants Analyzed 
[Units: Participants]
 148   146   294 
Hispanic or Latino   3   9   12 
Non-Hispanic and non-Latino       
Participants Analyzed 
[Units: Participants]
 148   146   294 
Non-Hispanic and non-Latino   144   137   281 
Unknown       
Participants Analyzed 
[Units: Participants]
 148   146   294 
Unknown   1   0   1 
Age group 
[Units: Participants]
Count of Participants
     
<=65 years       
Participants Analyzed 
[Units: Participants]
 148   146   294 
<=65 years   133   126   259 
>65 years       
Participants Analyzed 
[Units: Participants]
 148   146   294 
>65 years   15   20   35 
Body Mass Index 
[Units: Kg/m^2]
Mean (Standard Deviation)
     
Participants Analyzed 
[Units: Participants]
 148   146   294 
   32.8  (7.33)   33.0  (8.16)   32.9  (7.74) 
Type of Pain 
[Units: Participants]
Count of Participants
     
Low back pain       
Participants Analyzed 
[Units: Participants]
 148   146   294 
Low back pain   107   104   211 
Osteoarthritis       
Participants Analyzed 
[Units: Participants]
 148   146   294 
Osteoarthritis   41   42   83 
Duration since Diagnosis 
[Units: Years]
Mean (Standard Deviation)
     
Participants Analyzed 
[Units: Participants]
 148   146   294 
   12.5  (9.06)   12.1  (9.97)   12.3  (9.51) 
Participants on Opioid Therapy 
[Units: Participants]
Count of Participants
     
On opioid therapy       
Participants Analyzed 
[Units: Participants]
 148   146   294 
On opioid therapy   103   100   203 
Not on opioid therapy       
Participants Analyzed 
[Units: Participants]
 148   146   294 
Not on opioid therapy   45   46   91 
Duration of Opioid Therapy [1] 
[Units: Years]
Mean (Standard Deviation)
     
Participants Analyzed 
[Units: Participants]
 103   100   203 
   4.1  (4.90)   3.9  (4.76)   4.0  (4.82) 
[1] Includes participants with duration of opioid therapy data available.


  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Change From Baseline to Week 12 in Weekly Average Pain Intensity (wAPI)   [ Time Frame: Baseline (end of Open-Label Titration Period), Week 12 of Double-blind Treatment Period ]

2.  Secondary:   Percentage of Participants Withdrawn From the Study During the Double-Blind Treatment Period By Reason   [ Time Frame: Day 1 to Week 12 of the double-blind treatment period ]

3.  Secondary:   Kaplan-Meier Estimates for Time to Discontinuation From the Study   [ Time Frame: Day 1 to Week 12 of the double-blind treatment period ]

4.  Secondary:   Participants With a Weekly Average Pain Intensity (wAPI) Increase From Baseline Exceeding 33%   [ Time Frame: Baseline (end of Open-Label Titration Period), Weeks 1, 2, 4, 8, and 12 of the Double-blind treatment period ]

5.  Secondary:   Participants With a Weekly Average Pain Intensity (wAPI) Increase From Baseline Exceeding 50%   [ Time Frame: Baseline (end of Open-Label Titration Period), Weeks 1, 2, 4, 8, and 12 of the Double-blind treatment period ]

6.  Secondary:   Weekly Average Pain Intensity (wAPI) Scores During the Double-blind Treatment Period   [ Time Frame: Baseline (end of Open-Label Titration Period), Weeks 1, 2, 4, 8, and 12 of the Double-blind treatment period ]

7.  Secondary:   Weekly Average Worst Pain Intensity (WPI) Scores During the Double-blind Treatment Period   [ Time Frame: Baseline (end of Open-Label Titration Period), Weeks 1, 2, 4, 8, and 12 of the Double-blind treatment period ]

8.  Secondary:   Clinician Assessment of Patient Function (CAPF) at Week 4   [ Time Frame: Week 4 of the Double-blind Treatment Period ]

9.  Secondary:   Clinician Assessment of Patient Function (CAPF) at Week 8   [ Time Frame: Week 8 of the Double-blind Treatment Period ]

10.  Secondary:   Clinician Assessment of Patient Function (CAPF) at Week 12   [ Time Frame: Week 12 of the Double-blind Treatment Period ]

11.  Secondary:   Clinician Assessment of Patient Function (CAPF) at Endpoint   [ Time Frame: Endpoint of the Double-blind Treatment Period (up to week 12) ]

12.  Secondary:   Patient Assessment of Function (PAF) at Week 4   [ Time Frame: Week 4 of the Double-blind Treatment Period ]

13.  Secondary:   Patient Assessment of Function (PAF) at Week 8   [ Time Frame: Week 8 of the Double-blind Treatment Period ]

14.  Secondary:   Patient Assessment of Function (PAF) at Week 12   [ Time Frame: Week 12 of the Double-blind Treatment Period ]

15.  Secondary:   Patient Assessment of Function (PAF) at Endpoint   [ Time Frame: Endpoint of the Double-blind Treatment Period (up to week 12) ]

16.  Secondary:   Clinician Global Impression of Severity (CGI-S) of Illness Scores During the Double-blind Treatment Period   [ Time Frame: Baseline (end of Open-Label Titration Period), Weeks 1, 2, 4, 8, and 12 of the Double-blind treatment period ]

17.  Secondary:   Short-Form Health Survey (SF-36) Physical and Mental Component Summary Scores at Baseline, Week 12 and Endpoint   [ 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 ]

18.  Secondary:   Brief Pain Inventory – Short Form (BPI-SF) Pain Interference Mean Score During the Double-Blind Treatment Period   [ 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 ]

19.  Secondary:   Participants With Adverse Events   [ Time Frame: Day 1 up to Day 52 in Open-Label Titration; Day 1 up to Day 128 in Double-Blind Treatment period ]

20.  Secondary:   Participants With Potentially Clinically Significant Abnormal Vital Signs Values During the Double-Blind Treatment Period   [ Time Frame: Day 1 up to Day 128 in Double-Blind Treatment period ]

21.  Secondary:   Participants With Potentially Clinically Significant Abnormal Laboratory Values During the Double-Blind Treatment Period   [ Time Frame: Day 1 up to Day 128 in Double-Blind Treatment period ]

22.  Secondary:   Subjective Opiate Withdrawal Scales (SOWS) Scores During the Double-Blind Treatment Period   [ Time Frame: Weeks 1, 2, 4, 8, 12 and Endpoint (last visit up to Week 12) of the Double-blind treatment period ]

23.  Secondary:   Clinical Opiate Withdrawal Scales (COWS) Scores During the Double-Blind Treatment Period   [ 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 ]

24.  Secondary:   Addiction Behavior Checklist (ABC) Total Scores During Both the Open-Label Titration and Double-Blind Treatment Periods   [ 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 ]

25.  Secondary:   Current Opioid Misuse Measures (COMM) Total Scores During Both the Open-Label Titration and Double-Blind Treatment Periods   [ 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 ]

26.  Secondary:   Change From Baseline to Endpoint in the Double-Blind Treatment Phase in Electrocardiogram (ECG) Parameters   [ Time Frame: Baseline (end of Open-Label Titration Period), Endpoint (last visit up to Week 12) of the Double-blind treatment period ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
  Hide Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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  More Information
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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.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Director, Clinical Research
Organization: Teva Branded Pharmaceutical Products, R&D Inc
phone: 215-591-3000
e-mail: ustevatrials@tevapharm.com



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
Study First Received: November 10, 2010
Results First Received: February 19, 2017
Last Updated: June 2, 2017