Trial Outcomes & Findings for Study to Evaluate the Efficacy, Safety, Tolerability and Pharmacokinetics of AZD1386 in Patients With Osteoarthritis (OA) of the Knee (NCT NCT00878501)
NCT ID: NCT00878501
Last Updated: 2012-06-04
Results Overview
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.
TERMINATED
PHASE2
241 participants
Baseline, week 2, week 4.
2012-06-04
Participant Flow
International multi-center study, 41sites in North America, Japan and Europe recruited between March and July 2009. 327 participants enrolled into the study
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)
Participant milestones
| Measure |
Experimental 90 mg
AZD1386 90 mg twice a day (bid) for 4 weeks
|
Experimental 30 mg
AZD1386 30 mg twice a day (bid) for 4 weeks
|
Placebo Control
Placebo bid for 4 weeks
|
|---|---|---|---|
|
Overall Study
STARTED
|
104
|
44
|
93
|
|
Overall Study
Interim Analysis
|
83
|
37
|
81
|
|
Overall Study
COMPLETED
|
87
|
37
|
85
|
|
Overall Study
NOT COMPLETED
|
17
|
7
|
8
|
Reasons for withdrawal
| Measure |
Experimental 90 mg
AZD1386 90 mg twice a day (bid) for 4 weeks
|
Experimental 30 mg
AZD1386 30 mg twice a day (bid) for 4 weeks
|
Placebo Control
Placebo bid for 4 weeks
|
|---|---|---|---|
|
Overall Study
Adverse Event
|
11
|
3
|
3
|
|
Overall Study
Lack of Efficacy
|
2
|
1
|
0
|
|
Overall Study
Withdrawal by Subject
|
2
|
1
|
2
|
|
Overall Study
Protocol Violation
|
0
|
0
|
1
|
|
Overall Study
Incorrect enrolment
|
1
|
2
|
0
|
|
Overall Study
Intake of prohibited concom. medication
|
0
|
0
|
1
|
|
Overall Study
Mis-randomisation of patient
|
1
|
0
|
0
|
|
Overall Study
Administrative
|
0
|
0
|
1
|
Baseline Characteristics
Study to Evaluate the Efficacy, Safety, Tolerability and Pharmacokinetics of AZD1386 in Patients With Osteoarthritis (OA) of the Knee
Baseline characteristics by cohort
| Measure |
Experimental 90 mg
n=104 Participants
AZD1386 90 mg twice a day (bid) for 4 weeks
|
Experimental 30 mg
n=44 Participants
AZD1386 30 mg twice a day (bid) for 4 weeks
|
Placebo Control
n=93 Participants
Placebo bid for 4 weeks
|
Total
n=241 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age Continuous
median and range
|
62 Years
n=5 Participants
|
61 Years
n=7 Participants
|
61 Years
n=5 Participants
|
62 Years
n=4 Participants
|
|
Sex: Female, Male
Female
|
70 Participants
n=5 Participants
|
32 Participants
n=7 Participants
|
65 Participants
n=5 Participants
|
167 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
34 Participants
n=5 Participants
|
12 Participants
n=7 Participants
|
28 Participants
n=5 Participants
|
74 Participants
n=4 Participants
|
PRIMARY outcome
Timeframe: 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.
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.
Outcome measures
| Measure |
Experimental 90 mg
n=99 Participants
AZD1386 90 mg twice a day (bid) for 4 weeks
|
Experimental 30 mg
n=42 Participants
AZD1386 30 mg twice a day (bid) for 4 weeks
|
Placebo Control
n=90 Participants
Placebo bid for 4 weeks
|
|---|---|---|---|
|
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
Interval -22.89 to -15.21
|
-20.05 mm
Interval -25.75 to -14.34
|
-17.54 mm
Interval -21.55 to -13.52
|
SECONDARY outcome
Timeframe: 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.
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.
Outcome measures
| Measure |
Experimental 90 mg
n=99 Participants
AZD1386 90 mg twice a day (bid) for 4 weeks
|
Experimental 30 mg
n=42 Participants
AZD1386 30 mg twice a day (bid) for 4 weeks
|
Placebo Control
n=90 Participants
Placebo bid for 4 weeks
|
|---|---|---|---|
|
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
Interval -21.17 to -13.21
|
-18.84 mm
Interval -24.66 to -13.01
|
-17.12 mm
Interval -21.29 to -12.96
|
SECONDARY outcome
Timeframe: 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.
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.
Outcome measures
| Measure |
Experimental 90 mg
n=99 Participants
AZD1386 90 mg twice a day (bid) for 4 weeks
|
Experimental 30 mg
n=42 Participants
AZD1386 30 mg twice a day (bid) for 4 weeks
|
Placebo Control
n=90 Participants
Placebo bid for 4 weeks
|
|---|---|---|---|
|
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
Interval -20.19 to -11.91
|
-17.49 mm
Interval -23.62 to -11.37
|
-17.48 mm
Interval -21.82 to -13.14
|
SECONDARY outcome
Timeframe: 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.
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.
Outcome measures
| Measure |
Experimental 90 mg
n=99 Participants
AZD1386 90 mg twice a day (bid) for 4 weeks
|
Experimental 30 mg
n=42 Participants
AZD1386 30 mg twice a day (bid) for 4 weeks
|
Placebo Control
n=90 Participants
Placebo bid for 4 weeks
|
|---|---|---|---|
|
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
Interval -21.35 to -13.61
|
-18.93 mm
Interval -24.63 to -13.24
|
-17.27 mm
Interval -21.33 to -13.22
|
Adverse Events
Experimental 90 mg
Experimental 30 mg
Placebo Control
Serious adverse events
| Measure |
Experimental 90 mg
n=103 participants at risk
AZD1386 90 mg twice a day (bid) for 4 weeks
|
Experimental 30 mg
n=44 participants at risk
AZD1386 30 mg twice a day (bid) for 4 weeks
|
Placebo Control
n=93 participants at risk
Placebo bid for 4 weeks
|
|---|---|---|---|
|
Cardiac disorders
Acute Myocardial Infarction
|
0.00%
0/103
One participant in the Experimental 90 mg Arm did not receive study drug since incorrectly enrolled and is therefore not included.
|
0.00%
0/44
One participant in the Experimental 90 mg Arm did not receive study drug since incorrectly enrolled and is therefore not included.
|
1.1%
1/93
One participant in the Experimental 90 mg Arm did not receive study drug since incorrectly enrolled and is therefore not included.
|
|
Infections and infestations
Appendicitis
|
0.00%
0/103
One participant in the Experimental 90 mg Arm did not receive study drug since incorrectly enrolled and is therefore not included.
|
2.3%
1/44
One participant in the Experimental 90 mg Arm did not receive study drug since incorrectly enrolled and is therefore not included.
|
0.00%
0/93
One participant in the Experimental 90 mg Arm did not receive study drug since incorrectly enrolled and is therefore not included.
|
Other adverse events
| Measure |
Experimental 90 mg
n=103 participants at risk
AZD1386 90 mg twice a day (bid) for 4 weeks
|
Experimental 30 mg
n=44 participants at risk
AZD1386 30 mg twice a day (bid) for 4 weeks
|
Placebo Control
n=93 participants at risk
Placebo bid for 4 weeks
|
|---|---|---|---|
|
Nervous system disorders
Dysgeusia
|
14.6%
15/103
One participant in the Experimental 90 mg Arm did not receive study drug since incorrectly enrolled and is therefore not included.
|
4.5%
2/44
One participant in the Experimental 90 mg Arm did not receive study drug since incorrectly enrolled and is therefore not included.
|
1.1%
1/93
One participant in the Experimental 90 mg Arm did not receive study drug since incorrectly enrolled and is therefore not included.
|
|
Vascular disorders
Hot flush
|
7.8%
8/103
One participant in the Experimental 90 mg Arm did not receive study drug since incorrectly enrolled and is therefore not included.
|
11.4%
5/44
One participant in the Experimental 90 mg Arm did not receive study drug since incorrectly enrolled and is therefore not included.
|
3.2%
3/93
One participant in the Experimental 90 mg Arm did not receive study drug since incorrectly enrolled and is therefore not included.
|
|
Gastrointestinal disorders
Hypoaesthesia oral
|
9.7%
10/103
One participant in the Experimental 90 mg Arm did not receive study drug since incorrectly enrolled and is therefore not included.
|
4.5%
2/44
One participant in the Experimental 90 mg Arm did not receive study drug since incorrectly enrolled and is therefore not included.
|
3.2%
3/93
One participant in the Experimental 90 mg Arm did not receive study drug since incorrectly enrolled and is therefore not included.
|
|
Skin and subcutaneous tissue disorders
Hyperhidrosis
|
7.8%
8/103
One participant in the Experimental 90 mg Arm did not receive study drug since incorrectly enrolled and is therefore not included.
|
6.8%
3/44
One participant in the Experimental 90 mg Arm did not receive study drug since incorrectly enrolled and is therefore not included.
|
0.00%
0/93
One participant in the Experimental 90 mg Arm did not receive study drug since incorrectly enrolled and is therefore not included.
|
|
General disorders
Feeling cold
|
6.8%
7/103
One participant in the Experimental 90 mg Arm did not receive study drug since incorrectly enrolled and is therefore not included.
|
2.3%
1/44
One participant in the Experimental 90 mg Arm did not receive study drug since incorrectly enrolled and is therefore not included.
|
1.1%
1/93
One participant in the Experimental 90 mg Arm did not receive study drug since incorrectly enrolled and is therefore not included.
|
|
Nervous system disorders
Hypoaesthesia
|
5.8%
6/103
One participant in the Experimental 90 mg Arm did not receive study drug since incorrectly enrolled and is therefore not included.
|
2.3%
1/44
One participant in the Experimental 90 mg Arm did not receive study drug since incorrectly enrolled and is therefore not included.
|
1.1%
1/93
One participant in the Experimental 90 mg Arm did not receive study drug since incorrectly enrolled and is therefore not included.
|
|
Injury, poisoning and procedural complications
Thermal burn
|
3.9%
4/103
One participant in the Experimental 90 mg Arm did not receive study drug since incorrectly enrolled and is therefore not included.
|
6.8%
3/44
One participant in the Experimental 90 mg Arm did not receive study drug since incorrectly enrolled and is therefore not included.
|
0.00%
0/93
One participant in the Experimental 90 mg Arm did not receive study drug since incorrectly enrolled and is therefore not included.
|
|
Nervous system disorders
Headache
|
2.9%
3/103
One participant in the Experimental 90 mg Arm did not receive study drug since incorrectly enrolled and is therefore not included.
|
2.3%
1/44
One participant in the Experimental 90 mg Arm did not receive study drug since incorrectly enrolled and is therefore not included.
|
5.4%
5/93
One participant in the Experimental 90 mg Arm did not receive study drug since incorrectly enrolled and is therefore not included.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: OTHER