Pain
Conditions
Keywords
Phase II, Pain
Brief summary
The primary aim of this study is to investigate if AZD1386 is efficacious as an analgesic in patients with osteoarthritis of the knee and at what dose. This will be done by comparing the effect of AZD1386 to placebo (inactive substance) on pain.
Interventions
DRUGAZD1386
oral, during 4 weeks
DRUGPlacebo
Oral, during 4 weeks
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
40 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Patients with OA of the knee * Male or non pregnant females 40 and 80 years old
Exclusion criteria
* A current diagnosis of another form of arthritis, in addition to OA * History, and/or presence of somatic disease, which may interfere with the objectives
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean of Week 2 and Week 4 Changes From Baseline in Western Ontario and McMaster Universities Arthritis Index (WOMAC) Pain Subscale, 48 Hours Recall. | Baseline, week 2, week 4. | The WOMAC pain subscale is a self-administered electronic scale with 5 questions (Walking on flat surface, Going up or down stairs, At night while in bed, Sitting or lying, Standing upright). Responses were recorded on a 50-mm line with 100 units. 0 mm indicated no pain and 50 mm indicated extreme pain. The scores were then converted to a 100-mm scale. WOMAC pain was derived by calculating the mean of the VAS scores from the 5 questions with score scale ranging from 0 to 100, 0 being no pain and 100 extreme pain. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean of Week 2 and Week 4 Changes From Baseline in Western Ontario and McMaster Universities Arthritis Index (WOMAC) Function Subscale, 48 Hours Recall. | Baseline, Week 2 and Week 4. | The WOMAC VA 3.1. is a self-administered electronic questionnaire that assesses pain, stiffness and disability related to OA. The Function (daily activities) subscale consists of 17 questions. WOMAC function was derived by calculating the mean of the VAS scores from the 17 questions with scores ranging from 0 to 100, 0 = no difficulty in performing daily activities and 100 = extreme difficulty. |
| Mean of Week 2 and Week 4 Changes From Baseline in Western Ontario and McMaster Universities Arthritis Index (WOMAC) Stiffness Subscale, 48 Hours Recall. | Baseline, Week 2 and Week 4. | The WOMAC VA3.1. is a self-administered questionnaire that assesses pain, stiffness and disability related to osteoarthritis. The Stiffness subscale consists of 2 questions (Severity of stiffness after first awakening in the morning and severity of stiffnes after periods of inactivity later in the day). WOMAC stiffness was derived by calculating the mean of the VAS scores from the 2 questions with score scale ranging from 0 to 100, 0 being no stiffness and 100 extreme stiffness. |
| Mean of Week 2 and Week 4 Changes From Baseline in Western Ontario and McMaster Universities Arthritis Index (WOMAC) Total Score, 48 Hours Recall | Baseline, Week 2 and Week 4. | The WOMAC VA3.1. is a self-administered questionnaire that assesses pain, stiffness and disability related to osteoarthritis. It consists of a pain subscale (5 questions), function subscale (17 questions). and a stiffness subscale (2 questions). The total score was derived by calculating the mean of the VAS scores from all 24 questions with score scale ranging from 0 to 100, 0 being no pain, stiffness and difficulty in performing daily activities and 100 being extreme pain, stiffness and difficulty in performing daily activities. |
Countries
Bulgaria, Canada, Finland, Hungary, Japan, Poland, Slovakia
Participant flow
Recruitment details
International multi-center study, 41sites in North America, Japan and Europe recruited between March and July 2009. 327 participants enrolled into the study
Pre-assignment details
Patients with past or ongoing intolerability to NSAID´s/COX-2's or paracetamol/acetaminophen or patients with insufficient pain relief from these treatments were included in the study. The WOMAC pain on walking had to be ≥40 mm and ≤90 mm on a Visual Analogue Scale (VAS) at both enrolment and after 1 weeks wash-out of medication (randomisation)
Participants by arm
| Arm | Count |
|---|---|
| Experimental 90 mg AZD1386 90 mg twice a day (bid) for 4 weeks | 104 |
| Experimental 30 mg AZD1386 30 mg twice a day (bid) for 4 weeks | 44 |
| Placebo Control Placebo bid for 4 weeks | 93 |
| Total | 241 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Administrative | 0 | 0 | 1 |
| Overall Study | Adverse Event | 11 | 3 | 3 |
| Overall Study | Incorrect enrolment | 1 | 2 | 0 |
| Overall Study | Intake of prohibited concom. medication | 0 | 0 | 1 |
| Overall Study | Lack of Efficacy | 2 | 1 | 0 |
| Overall Study | Mis-randomisation of patient | 1 | 0 | 0 |
| Overall Study | Protocol Violation | 0 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 2 | 1 | 2 |
Baseline characteristics
| Characteristic | Total | Experimental 90 mg | Experimental 30 mg | Placebo Control |
|---|---|---|---|---|
| Age Continuous median and range | 62 Years | 62 Years | 61 Years | 61 Years |
| Sex: Female, Male Female | 167 Participants | 70 Participants | 32 Participants | 65 Participants |
| Sex: Female, Male Male | 74 Participants | 34 Participants | 12 Participants | 28 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 61 / 103 | 15 / 44 | 14 / 93 |
| serious Total, serious adverse events | 0 / 103 | 1 / 44 | 1 / 93 |
Outcome results
Primary
Mean of Week 2 and Week 4 Changes From Baseline in Western Ontario and McMaster Universities Arthritis Index (WOMAC) Pain Subscale, 48 Hours Recall.
The WOMAC pain subscale is a self-administered electronic scale with 5 questions (Walking on flat surface, Going up or down stairs, At night while in bed, Sitting or lying, Standing upright). Responses were recorded on a 50-mm line with 100 units. 0 mm indicated no pain and 50 mm indicated extreme pain. The scores were then converted to a 100-mm scale. WOMAC pain was derived by calculating the mean of the VAS scores from the 5 questions with score scale ranging from 0 to 100, 0 being no pain and 100 extreme pain.
Time frame: Baseline, week 2, week 4.
Population: Number of Participants Analyzed for the stated measure are defined according to the Modified Intention To Treat analysis set whereas numbers provided in the Participant Flow Module correspond to number of participants enrolled.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Experimental 90 mg | Mean of Week 2 and Week 4 Changes From Baseline in Western Ontario and McMaster Universities Arthritis Index (WOMAC) Pain Subscale, 48 Hours Recall. | -19.05 mm |
| Experimental 30 mg | Mean of Week 2 and Week 4 Changes From Baseline in Western Ontario and McMaster Universities Arthritis Index (WOMAC) Pain Subscale, 48 Hours Recall. | -20.05 mm |
| Placebo Control | Mean of Week 2 and Week 4 Changes From Baseline in Western Ontario and McMaster Universities Arthritis Index (WOMAC) Pain Subscale, 48 Hours Recall. | -17.54 mm |
Secondary
Mean of Week 2 and Week 4 Changes From Baseline in Western Ontario and McMaster Universities Arthritis Index (WOMAC) Function Subscale, 48 Hours Recall.
The WOMAC VA 3.1. is a self-administered electronic questionnaire that assesses pain, stiffness and disability related to OA. The Function (daily activities) subscale consists of 17 questions. WOMAC function was derived by calculating the mean of the VAS scores from the 17 questions with scores ranging from 0 to 100, 0 = no difficulty in performing daily activities and 100 = extreme difficulty.
Time frame: Baseline, Week 2 and Week 4.
Population: Number of Participants Analyzed for the stated measure are defined according to the Modified Intention To Treat analysis set whereas numbers provided in the Participant Flow Module correspond to number of participants enrolled.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Experimental 90 mg | Mean of Week 2 and Week 4 Changes From Baseline in Western Ontario and McMaster Universities Arthritis Index (WOMAC) Function Subscale, 48 Hours Recall. | -17.19 mm |
| Experimental 30 mg | Mean of Week 2 and Week 4 Changes From Baseline in Western Ontario and McMaster Universities Arthritis Index (WOMAC) Function Subscale, 48 Hours Recall. | -18.84 mm |
| Placebo Control | Mean of Week 2 and Week 4 Changes From Baseline in Western Ontario and McMaster Universities Arthritis Index (WOMAC) Function Subscale, 48 Hours Recall. | -17.12 mm |
Secondary
Mean of Week 2 and Week 4 Changes From Baseline in Western Ontario and McMaster Universities Arthritis Index (WOMAC) Stiffness Subscale, 48 Hours Recall.
The WOMAC VA3.1. is a self-administered questionnaire that assesses pain, stiffness and disability related to osteoarthritis. The Stiffness subscale consists of 2 questions (Severity of stiffness after first awakening in the morning and severity of stiffnes after periods of inactivity later in the day). WOMAC stiffness was derived by calculating the mean of the VAS scores from the 2 questions with score scale ranging from 0 to 100, 0 being no stiffness and 100 extreme stiffness.
Time frame: Baseline, Week 2 and Week 4.
Population: Number of Participants Analyzed for the stated measure are defined according to the Modified Intention To Treat analysis set whereas numbers provided in the Participant Flow Module correspond to number of participants enrolled.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Experimental 90 mg | Mean of Week 2 and Week 4 Changes From Baseline in Western Ontario and McMaster Universities Arthritis Index (WOMAC) Stiffness Subscale, 48 Hours Recall. | -16.05 mm |
| Experimental 30 mg | Mean of Week 2 and Week 4 Changes From Baseline in Western Ontario and McMaster Universities Arthritis Index (WOMAC) Stiffness Subscale, 48 Hours Recall. | -17.49 mm |
| Placebo Control | Mean of Week 2 and Week 4 Changes From Baseline in Western Ontario and McMaster Universities Arthritis Index (WOMAC) Stiffness Subscale, 48 Hours Recall. | -17.48 mm |
Secondary
Mean of Week 2 and Week 4 Changes From Baseline in Western Ontario and McMaster Universities Arthritis Index (WOMAC) Total Score, 48 Hours Recall
The WOMAC VA3.1. is a self-administered questionnaire that assesses pain, stiffness and disability related to osteoarthritis. It consists of a pain subscale (5 questions), function subscale (17 questions). and a stiffness subscale (2 questions). The total score was derived by calculating the mean of the VAS scores from all 24 questions with score scale ranging from 0 to 100, 0 being no pain, stiffness and difficulty in performing daily activities and 100 being extreme pain, stiffness and difficulty in performing daily activities.
Time frame: Baseline, Week 2 and Week 4.
Population: Number of Participants Analyzed for the stated measure are defined according to the Modified Intention To Treat analysis set whereas numbers provided in the Participant Flow Module correspond to number of participants enrolled.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Experimental 90 mg | Mean of Week 2 and Week 4 Changes From Baseline in Western Ontario and McMaster Universities Arthritis Index (WOMAC) Total Score, 48 Hours Recall | -17.48 mm |
| Experimental 30 mg | Mean of Week 2 and Week 4 Changes From Baseline in Western Ontario and McMaster Universities Arthritis Index (WOMAC) Total Score, 48 Hours Recall | -18.93 mm |
| Placebo Control | Mean of Week 2 and Week 4 Changes From Baseline in Western Ontario and McMaster Universities Arthritis Index (WOMAC) Total Score, 48 Hours Recall | -17.27 mm |