ClinicalTrials.gov
ClinicalTrials.gov Menu

Placebo-controlled Trial With OROS Hydromorphone Hydrochloride to Treat Patients With Moderate to Severe Pain Induced by Osteoarthritis of the Hip or the Knee

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: NCT00980798
Recruitment Status : Completed
First Posted : September 21, 2009
Results First Posted : September 6, 2010
Last Update Posted : April 25, 2014
Sponsor:
Information provided by (Responsible Party):
Janssen-Cilag International NV

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Conditions Pain
Osteoarthritis, Hip
Osteoarthritis, Knee
Interventions Drug: OROS hydromorphone HCl
Drug: Placebo
Enrollment 288

Recruitment Details The first subject attended the first study visit on 05 October 2007, and the last subject completed the last study visit on 24 November 2008.
Pre-assignment Details  
Arm/Group Title Placebo OROS Hydromorphone HCl
Hide Arm/Group Description Placebo daily for 16 weeks 4 to 32 mg taken orally once daily for 16 weeks
Period Title: Overall Study
Started 149 139
Completed 116 84
Not Completed 33 55
Reason Not Completed
Adverse Event             7             36
Lack of Efficacy             16             5
Lost to Follow-up             0             1
Physician Decision             2             1
Withdrawal by Subject             8             11
Other             0             1
Arm/Group Title Placebo OROS Hydromorphone HCl Total
Hide Arm/Group Description Placebo daily for 16 weeks 4 to 32 mg taken orally once daily for 16 weeks Total of all reporting groups
Overall Number of Baseline Participants 149 139 288
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 149 participants 139 participants 288 participants
64.9  (10.37) 65.1  (9.96) 65  (10.16)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 149 participants 139 participants 288 participants
Female
101
  67.8%
107
  77.0%
208
  72.2%
Male
48
  32.2%
32
  23.0%
80
  27.8%
1.Primary Outcome
Title Analgesic Effect as Assessed by Brief Pain Inventory (BPI) Item 5 Score (Pain on Average)
Hide Description The analgesic effect was assessed by the BPI item 5 “pain on average” using a 0 to 10 numeric rating scale, with 0 being "no pain" and 10 being "pain as bad as you can imagine".
Time Frame At each study visit from screening to week 16
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The primary population for the efficacy analyses was the intention to treat (ITT) population: all randomised patients who received at least one dose of study drug excluding patients who had no post-baseline efficacy data. This population included patients who discontinued early owing to lack of efficacy or other reasons.
Arm/Group Title Placebo OROS Hydromorphone HCl
Hide Arm/Group Description:
Placebo daily for 16 weeks
4 to 32 mg taken orally once daily for 16 weeks
Overall Number of Participants Analyzed 143 132
Mean (Standard Deviation)
Unit of Measure: units on a scale
Screening 6.4  (0.94) 6.4  (1.05)
Baseline (Visit 1) 6.5  (0.94) 6.6  (1.04)
Visit 2 5.2  (1.43) 5.0  (1.63)
Visit 3 4.8  (1.66) 4.6  (1.66)
Visit 4 4.3  (1.72) 4.0  (1.85)
Visit 5 3.9  (1.9) 3.9  (2.02)
Visit 6 3.7  (1.97) 3.5  (1.88)
Visit 7 3.6  (1.99) 3.4  (1.96)
Visit 8 4.0  (2.3) 4.1  (2.2)
Visit 9 4.2  (2.27) 4.4  (2.23)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, OROS Hydromorphone HCl
Comments The F test for treatment tested the null hypothesis of no treatment difference. Assuming that 3 baseline measures and 7 post baseline measures were collected 81 patients were required per group to detect a difference of 1 point in the BPI measure with 90% power at a significance level of 5%. To allow for a drop-out rate of approximately 40%, the study planned to recruit 135 patients per group (i.e. 270 in total).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1212
Comments No adjustment for multiple comparisons necessary, as only 1 primary hypothesis was tested. Threshold for statistical significance was 0.05.
Method Mixed-model regression analysis
Comments The difference above is presented as the difference OROS hydromorphone HCl minus placebo, so negative scores favour OROS hydromorphone HCl.
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.2365
Confidence Interval (2-Sided) 95%
-0.5357 to 0.0627
Estimation Comments The analysis was adjusted for baseline BPI item 5 score, time on study, and whether the primary affected joint was the hip or knee.
2.Secondary Outcome
Title The Number of Patients Discontinuing From the Trial Due to the Occurrence of an Adverse Event
Hide Description The number of patients dropping out of the study owing to adverse events will be presented for each treatment group.
Time Frame At each study visit from baseline until week 16
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Safety population: All randomised patients who received at least one dose of study drug.
Arm/Group Title Placebo OROS Hydromorphone HCl
Hide Arm/Group Description:
Placebo daily for 16 weeks
4 to 32 mg taken orally once daily for 16 weeks
Overall Number of Participants Analyzed 149 139
Measure Type: Number
Unit of Measure: participants
7 36
Time Frame Adverse were collected from signing of informed consent until the end of the study (week 16 or later after complete tapering off of study medication)
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Placebo OROS Hydromorphone HCl
Hide Arm/Group Description Placebo daily for 16 weeks 4 to 32 mg taken orally once daily for 16 weeks
All-Cause Mortality
Placebo OROS Hydromorphone HCl
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Placebo OROS Hydromorphone HCl
Affected / at Risk (%) Affected / at Risk (%)
Total   7/149 (4.70%)   4/139 (2.88%) 
Cardiac disorders     
Atrial fibrillation * 1  1/149 (0.67%)  0/139 (0.00%) 
Myocardial infarction * 1  1/149 (0.67%)  0/139 (0.00%) 
Supraventricular tachycardia * 1  1/149 (0.67%)  0/139 (0.00%) 
Gastrointestinal disorders     
Dyspepsia * 1  0/149 (0.00%)  2/139 (1.44%) 
Abdominal pain upper * 1  0/149 (0.00%)  1/139 (0.72%) 
Diarrhoea * 1  0/149 (0.00%)  1/139 (0.72%) 
Nausea * 1  0/149 (0.00%)  1/139 (0.72%) 
General disorders     
Asthenia * 1  0/149 (0.00%)  1/139 (0.72%) 
Infections and infestations     
Pyelonephritis acute * 1  1/149 (0.67%)  0/139 (0.00%) 
Injury, poisoning and procedural complications     
Skin laceration * 1  0/149 (0.00%)  1/139 (0.72%) 
Road traffic accident * 1  1/149 (0.67%)  0/139 (0.00%) 
Metabolism and nutrition disorders     
Hyperglycaemia * 1  1/149 (0.67%)  0/139 (0.00%) 
Nervous system disorders     
Cerebrovascular accident * 1  1/149 (0.67%)  1/139 (0.72%) 
Skin and subcutaneous tissue disorders     
Dermatitis allergic * 1  1/149 (0.67%)  0/139 (0.00%) 
Surgical and medical procedures     
Cardioversion * 1  1/149 (0.67%)  0/139 (0.00%) 
Vascular disorders     
Hypertensive crisis * 1  0/149 (0.00%)  1/139 (0.72%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA 11.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Placebo OROS Hydromorphone HCl
Affected / at Risk (%) Affected / at Risk (%)
Total   50/149 (33.56%)   106/139 (76.26%) 
Ear and labyrinth disorders     
Vertigo * 1  4/149 (2.68%)  10/139 (7.19%) 
Gastrointestinal disorders     
Constipation * 1  10/149 (6.71%)  63/139 (45.32%) 
Nausea * 1  10/149 (6.71%)  41/139 (29.50%) 
Vomiting * 1  2/149 (1.34%)  15/139 (10.79%) 
Dry mouth * 1  7/149 (4.70%)  11/139 (7.91%) 
Metabolism and nutrition disorders     
Anorexia * 1  1/149 (0.67%)  8/139 (5.76%) 
Nervous system disorders     
Somnolence * 1  22/149 (14.77%)  45/139 (32.37%) 
Dizziness * 1  5/149 (3.36%)  15/139 (10.79%) 
Headache * 1  4/149 (2.68%)  8/139 (5.76%) 
Skin and subcutaneous tissue disorders     
Pruritus * 1  1/149 (0.67%)  10/139 (7.19%) 
Hyperhidrosis * 1  0/149 (0.00%)  7/139 (5.04%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA 11.0
Concomitant and rescue medication were permitted in the study. This may be why the results in the placebo arm so closely resemble those in the treatment arm. Patients were also less severely impacted by the underlying disease than in other studies.
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: EMEA Medical Affairs Director Analgesia
Organization: Janssen-Cilag Ireland
Phone: 0035 878 339174
Responsible Party: Janssen-Cilag International NV
ClinicalTrials.gov Identifier: NCT00980798     History of Changes
Other Study ID Numbers: CR012601
HOP Trial
First Submitted: September 18, 2009
First Posted: September 21, 2009
Results First Submitted: August 12, 2010
Results First Posted: September 6, 2010
Last Update Posted: April 25, 2014