Osteoarthritis, Hip, Osteoarthritis, Knee, Pain
Conditions
Keywords
Osteoarthritis, Strong pain killer, Strong opioid, Low starting dose, Fewer side effects, Physical functioning, Pain control, Quality of life, Sleep quality
Brief summary
This clinical trial tests the pain relieving effectiveness of OROS hydromorphone, a once-daily formulation of a strong opioid against placebo in patients, who are suffering from pain due to osteoarthritis of the hip or the knee and who previously did not receive any strong opioids.The clinical trial tests the effect of the treatment on symptoms of pain, stiffness and physical function. The effect of the treatment on parameters on health related quality of life as well as quality of sleep will be measured.
Detailed description
In this clinical trial subjects are enrolled, who are suffering from pain due to osteoarthritis of the hip or the knee that is not sufficiently controlled with either a non steroidal anti-inflammatory drug (NSAID) or paracetamol or a weak opioid. This clinical trial tests the pain relieving effectiveness of OROS hydromorphone, a once-daily formulation of a strong opioid against placebo in patients, who previously did not receive any strong opioids. The drug class of opioid analgesics can broadly be classified into strong and weak. Weak opioids (for example tramadol, codeine, dihydrocodeine and tilidine) are useful for mild to moderate pain and the strong opioids (for example morphine, fentanyl and hydromorphone) are useful for moderate to severe pain of different origin. OROS hydromorphone is an opioid, which is available in a prolonged-release tablet in different dosage strengths. The primary aim of the study is to test the efficacy of OROS hydromorphone against placebo at an individual dose sufficient to control the pain and to establish the usefulness of a new low-dose formulation of OROS hydromorphone (4 mg hydromorphone per tablet) for initiating the treatment and for dose titration. The clinical trial tests the effect of the treatment on symptoms of pain, stiffness and physical function. The effect of the treatment on parameters on health related quality of life as well as quality of sleep will be measured. The safety of the treatment will be recorded by measuring blood pressure, heart rate, and respiratory rate.This clinical trial is a placebo-controlled trial, meaning that one group of patients will receive the drug to be tested (OROS hydromorphone) while the control group receives an optically identical tablet with no active ingredient, a so-called placebo. A total number of 270 patients will be enrolled in this clinical trial and assigned to one of two treatment arms at an equal ratio (i.e. 135 patients per treatment). Patients will be randomly assigned to one of the two treatment arms, like flipping a coin to decide which treatment they will receive. Neither the patient nor the doctor will know to which of the two treatment arms the patient is assigned to and neither the patient nor the doctor can influence the assignment to the treatment arm. During the whole treatment period paracetamol will be allowed to be taken as needed in case of pain. Medical history and physical exam will be conducted during the screening visit, followed in 1 week by the baseline visit where after completing several questionnaires assessing pain, physical functioning quality of life and sleep quality, the patient will be assigned to one of two treatment groups. After starting the study treatment the patient will visit the doctor 7 times: at week 1, 2, 3, 4, 8, 12, 16 and at a follow-up visit after the end of the treatment period at week 16. At week 16 questionnaires will again be completed and the results will be compared to the baseline findings. 4, 8, 12, 16, 24 or 32 mg of OROS hydromorphone tablets or matching placebo tablets taken for 16 weeks. All tablets are taken by mouth at the same time each day in the morning. Tablets have to be swallowed whole without chewing or crushing. After completion of the treatment duration (or at early withdrawal), the study medication is gradually tapered down over a maximum of 6 days.
Interventions
4 to 32 mg taken orally once daily for 16 weeks
DRUGPlacebo
placebo tablet once daily for 16 weeks
Sponsors
Janssen-Cilag International NV
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
40 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Documented Osteoarthritis of the hip or knee * Chronic pain for more than 3 months treated with daily analgesic for the last month * Moderate to severe OA pain of the target joint, which cannot be adequately treated with non-steroidal anti-inflamatory drugs or paracetamol * Moderate to severe pain by means of a mean weekly score of \>= 5 in the Brief Pain Invetory item 5 'pain on average'
Exclusion criteria
* Regular treatment with an opioid in the 4 weeks before screening visit (infrequent use of tramadol, codeine, tilidine, or dihydrocodeine for no more than 10 days in the 4 weeks before the screening visit is acceptable, however, treatment must be stopped at screening visit) * Diagnosis of major depression * Treatment for epilepsy * Corticosteroid injection within the last 3 months * Major surgery in the 3 months before the start of the study * Women who are pregnant or breast-feeding
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Analgesic Effect as Assessed by Brief Pain Inventory (BPI) Item 5 Score (Pain on Average) | At each study visit from screening to week 16 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The Number of Patients Discontinuing From the Trial Due to the Occurrence of an Adverse Event | At each study visit from baseline until week 16 | The number of patients dropping out of the study owing to adverse events will be presented for each treatment group. |
Countries
Czechia, Romania, Slovakia, United Kingdom
Participant flow
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.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Placebo daily for 16 weeks | 149 |
| OROS Hydromorphone HCl 4 to 32 mg taken orally once daily for 16 weeks | 139 |
| Total | 288 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 7 | 36 |
| Overall Study | Lack of Efficacy | 16 | 5 |
| Overall Study | Lost to Follow-up | 0 | 1 |
| Overall Study | Other | 0 | 1 |
| Overall Study | Physician Decision | 2 | 1 |
| Overall Study | Withdrawal by Subject | 8 | 11 |
Baseline characteristics
| Characteristic | Placebo | OROS Hydromorphone HCl | Total |
|---|---|---|---|
| Age, Continuous | 64.9 years STANDARD_DEVIATION 10.37 | 65.1 years STANDARD_DEVIATION 9.96 | 65 years STANDARD_DEVIATION 10.16 |
| Sex: Female, Male Female | 101 Participants | 107 Participants | 208 Participants |
| Sex: Female, Male Male | 48 Participants | 32 Participants | 80 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 50 / 149 | 106 / 139 |
| serious Total, serious adverse events | 7 / 149 | 4 / 139 |
Outcome results
Primary
Analgesic Effect as Assessed by Brief Pain Inventory (BPI) Item 5 Score (Pain on Average)
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
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Analgesic Effect as Assessed by Brief Pain Inventory (BPI) Item 5 Score (Pain on Average) | Visit 2 | 5.2 units on a scale | Standard Deviation 1.43 |
| Placebo | Analgesic Effect as Assessed by Brief Pain Inventory (BPI) Item 5 Score (Pain on Average) | Visit 5 | 3.9 units on a scale | Standard Deviation 1.9 |
| Placebo | Analgesic Effect as Assessed by Brief Pain Inventory (BPI) Item 5 Score (Pain on Average) | Baseline (Visit 1) | 6.5 units on a scale | Standard Deviation 0.94 |
| Placebo | Analgesic Effect as Assessed by Brief Pain Inventory (BPI) Item 5 Score (Pain on Average) | Visit 6 | 3.7 units on a scale | Standard Deviation 1.97 |
| Placebo | Analgesic Effect as Assessed by Brief Pain Inventory (BPI) Item 5 Score (Pain on Average) | Visit 3 | 4.8 units on a scale | Standard Deviation 1.66 |
| Placebo | Analgesic Effect as Assessed by Brief Pain Inventory (BPI) Item 5 Score (Pain on Average) | Visit 7 | 3.6 units on a scale | Standard Deviation 1.99 |
| Placebo | Analgesic Effect as Assessed by Brief Pain Inventory (BPI) Item 5 Score (Pain on Average) | Screening | 6.4 units on a scale | Standard Deviation 0.94 |
| Placebo | Analgesic Effect as Assessed by Brief Pain Inventory (BPI) Item 5 Score (Pain on Average) | Visit 8 | 4.0 units on a scale | Standard Deviation 2.3 |
| Placebo | Analgesic Effect as Assessed by Brief Pain Inventory (BPI) Item 5 Score (Pain on Average) | Visit 4 | 4.3 units on a scale | Standard Deviation 1.72 |
| Placebo | Analgesic Effect as Assessed by Brief Pain Inventory (BPI) Item 5 Score (Pain on Average) | Visit 9 | 4.2 units on a scale | Standard Deviation 2.27 |
| OROS Hydromorphone HCl | Analgesic Effect as Assessed by Brief Pain Inventory (BPI) Item 5 Score (Pain on Average) | Visit 9 | 4.4 units on a scale | Standard Deviation 2.23 |
| OROS Hydromorphone HCl | Analgesic Effect as Assessed by Brief Pain Inventory (BPI) Item 5 Score (Pain on Average) | Screening | 6.4 units on a scale | Standard Deviation 1.05 |
| OROS Hydromorphone HCl | Analgesic Effect as Assessed by Brief Pain Inventory (BPI) Item 5 Score (Pain on Average) | Baseline (Visit 1) | 6.6 units on a scale | Standard Deviation 1.04 |
| OROS Hydromorphone HCl | Analgesic Effect as Assessed by Brief Pain Inventory (BPI) Item 5 Score (Pain on Average) | Visit 2 | 5.0 units on a scale | Standard Deviation 1.63 |
| OROS Hydromorphone HCl | Analgesic Effect as Assessed by Brief Pain Inventory (BPI) Item 5 Score (Pain on Average) | Visit 3 | 4.6 units on a scale | Standard Deviation 1.66 |
| OROS Hydromorphone HCl | Analgesic Effect as Assessed by Brief Pain Inventory (BPI) Item 5 Score (Pain on Average) | Visit 4 | 4.0 units on a scale | Standard Deviation 1.85 |
| OROS Hydromorphone HCl | Analgesic Effect as Assessed by Brief Pain Inventory (BPI) Item 5 Score (Pain on Average) | Visit 5 | 3.9 units on a scale | Standard Deviation 2.02 |
| OROS Hydromorphone HCl | Analgesic Effect as Assessed by Brief Pain Inventory (BPI) Item 5 Score (Pain on Average) | Visit 6 | 3.5 units on a scale | Standard Deviation 1.88 |
| OROS Hydromorphone HCl | Analgesic Effect as Assessed by Brief Pain Inventory (BPI) Item 5 Score (Pain on Average) | Visit 7 | 3.4 units on a scale | Standard Deviation 1.96 |
| OROS Hydromorphone HCl | Analgesic Effect as Assessed by Brief Pain Inventory (BPI) Item 5 Score (Pain on Average) | Visit 8 | 4.1 units on a scale | Standard Deviation 2.2 |
Comparison: 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).p-value: 0.121295% CI: [-0.5357, 0.0627]Mixed-model regression analysis
Secondary
The Number of Patients Discontinuing From the Trial Due to the Occurrence of an Adverse Event
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
Population: Safety population: All randomised patients who received at least one dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | The Number of Patients Discontinuing From the Trial Due to the Occurrence of an Adverse Event | 7 participants |
| OROS Hydromorphone HCl | The Number of Patients Discontinuing From the Trial Due to the Occurrence of an Adverse Event | 36 participants |