Trial Outcomes & Findings for A 12-Week Efficacy Study of Paracetamol 1000mg Sustained-release Tablets in Patients With Osteoarthritis (NCT NCT02311881)
NCT ID: NCT02311881
Last Updated: 2017-04-07
Results Overview
The WOMAC Osteoarthritis Index is a 24-item questionnaire that assesses pain, physical function, and stiffness in the target joint. WOMAC Pain was measured using visual analogue scale (VAS) ranging from 0mm (no pain) to 100mm (extreme pain) at baseline and at week 1, 2, 4, 8, and 12. Lower values represent a better outcome. At each time point the assessment included 5 WOMAC Pain items: 1-walking on flat, 2-going up down stairs, 3-at night while in bed, 4-sitting or lying; 5-standing upright. Mean WOMAC Pain subscale score was calculated at each visit as the sum of 5 pain category scores divided by 5. Change from baseline was calculated for each visit as the mean WOMAC Pain subscale score minus the mean baseline WOMAC Pain subscale score. A negative change from Baseline indicated improvement. The time-weighted mean change was calculated as the area under the curve of change from baseline divided by the nominal time of the last on-therapy visit (week 12) from randomization (baseline).
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
960 participants
Primary outcome timeframe
Baseline up to week 12
Results posted on
2017-04-07
Participant Flow
This study was conducted in 57 centers in United States.
A total of 1531 participants were screened for study. Out of which only 960 participants who completed screening visit \& took part in wash-out period were enrolled. Out of 960 enrolled participants, only 708 were randomized. 252 were not randomized because they did not fulfill specific inclusion criterion measured at the end of the wash-out period.
Participant milestones
| Measure |
Paracetamol 2000 mg Twice Daily (BID)
Participants were instructed to take two active paracetamol 1000 milligram (mg) sustained release (SR) tablets twice daily (with 10-12 hours between adjacent doses) and two placebo to match paracetamol 665 mg SR tablets thrice daily (with 6-8 hours between adjacent doses) orally with approximately 8 ounces ( ̴240 milliliter \[mL\]) of water/dose for 12 weeks.
|
Paracetamol 1330 mg Thrice Daily (TID)
Participants were instructed to take two active paracetamol 665 mg SR tablets orally thrice daily (with 6-8 hours between adjacent doses) and two placebo to match paracetamol 1000 mg SR tablets orally twice daily (with 10-12 hours between adjacent doses) orally with approximately 8 ounces ( ̴240 mL) of water/dose for 12 weeks.
|
Placebo
Participants were instructed to take two placebo to match paracetamol 1000 mg SR tablets twice daily (with 10-12 hours between adjacent doses) and two placebo to match paracetamol 665 mg SR tablets thrice daily (with 6-8 hours between adjacent doses) orally with approximately 8 ounces ( ̴240 mL) of water/dose for 12 weeks.
|
|---|---|---|---|
|
Overall Study
STARTED
|
235
|
236
|
237
|
|
Overall Study
Safety Population
|
234
|
236
|
237
|
|
Overall Study
COMPLETED
|
200
|
193
|
196
|
|
Overall Study
NOT COMPLETED
|
35
|
43
|
41
|
Reasons for withdrawal
| Measure |
Paracetamol 2000 mg Twice Daily (BID)
Participants were instructed to take two active paracetamol 1000 milligram (mg) sustained release (SR) tablets twice daily (with 10-12 hours between adjacent doses) and two placebo to match paracetamol 665 mg SR tablets thrice daily (with 6-8 hours between adjacent doses) orally with approximately 8 ounces ( ̴240 milliliter \[mL\]) of water/dose for 12 weeks.
|
Paracetamol 1330 mg Thrice Daily (TID)
Participants were instructed to take two active paracetamol 665 mg SR tablets orally thrice daily (with 6-8 hours between adjacent doses) and two placebo to match paracetamol 1000 mg SR tablets orally twice daily (with 10-12 hours between adjacent doses) orally with approximately 8 ounces ( ̴240 mL) of water/dose for 12 weeks.
|
Placebo
Participants were instructed to take two placebo to match paracetamol 1000 mg SR tablets twice daily (with 10-12 hours between adjacent doses) and two placebo to match paracetamol 665 mg SR tablets thrice daily (with 6-8 hours between adjacent doses) orally with approximately 8 ounces ( ̴240 mL) of water/dose for 12 weeks.
|
|---|---|---|---|
|
Overall Study
Did not meet the study criteria
|
2
|
2
|
0
|
|
Overall Study
Adverse Event
|
7
|
15
|
8
|
|
Overall Study
Lost to Follow-up
|
3
|
3
|
2
|
|
Overall Study
Protocol Violation
|
1
|
2
|
3
|
|
Overall Study
Withdrawal of consent
|
14
|
16
|
17
|
|
Overall Study
Other
|
0
|
0
|
1
|
|
Overall Study
Lack of Efficacy
|
1
|
2
|
0
|
|
Overall Study
Subject has border line pregnancy test
|
1
|
0
|
0
|
|
Overall Study
Withdrawal by Subject
|
3
|
1
|
4
|
|
Overall Study
Sponsor Decision
|
1
|
1
|
1
|
|
Overall Study
Protocol Deviation
|
1
|
0
|
0
|
|
Overall Study
Non-Compliance
|
1
|
0
|
2
|
|
Overall Study
Physician Decision
|
0
|
0
|
1
|
|
Overall Study
Medical Monitor Discretion
|
0
|
0
|
1
|
|
Overall Study
Participant taking another medication
|
0
|
0
|
1
|
|
Overall Study
Serious Adverse Event
|
0
|
1
|
0
|
Baseline Characteristics
A 12-Week Efficacy Study of Paracetamol 1000mg Sustained-release Tablets in Patients With Osteoarthritis
Baseline characteristics by cohort
| Measure |
Paracetamol 2000 mg Twice Daily (BID)
n=234 Participants
Participants were instructed to take two active paracetamol 1000 mg SR tablets twice daily (with 10-12 hours between adjacent doses) and two placebo to match paracetamol 665 mg SR tablets thrice daily (with 6-8 hours between adjacent doses) orally with approximately 8 ounces ( ̴240 mL) of water/dose for 12 weeks.
|
Paracetamol 1330 mg Thrice Daily (TID)
n=236 Participants
Participants were instructed to take two active paracetamol 665 mg SR tablets orally thrice daily (with 6-8 hours between adjacent doses) and two placebo to match paracetamol 1000 mg SR tablets orally twice daily (with 10-12 hours between adjacent doses) orally with approximately 8 ounces ( ̴240 mL) of water/dose for 12 weeks.
|
Placebo
n=237 Participants
Participants were instructed to take two placebo to match paracetamol 1000 mg SR tablets twice daily (with 10-12 hours between adjacent doses) and two placebo to match paracetamol 665 mg SR tablets thrice daily (with 6-8 hours between adjacent doses) orally with approximately 8 ounces ( ̴240 mL) of water/dose for 12 weeks.
|
Total
n=707 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
60.27 Years
STANDARD_DEVIATION 8.544 • n=5 Participants
|
60.47 Years
STANDARD_DEVIATION 8.410 • n=7 Participants
|
61.46 Years
STANDARD_DEVIATION 8.187 • n=5 Participants
|
60.73 Years
STANDARD_DEVIATION 8.385 • n=4 Participants
|
|
Sex: Female, Male
Female
|
146 Participants
n=5 Participants
|
147 Participants
n=7 Participants
|
150 Participants
n=5 Participants
|
443 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
88 Participants
n=5 Participants
|
89 Participants
n=7 Participants
|
87 Participants
n=5 Participants
|
264 Participants
n=4 Participants
|
|
Race/Ethnicity, Customized
Hispanic or Latino
|
77 number of participants
n=5 Participants
|
81 number of participants
n=7 Participants
|
95 number of participants
n=5 Participants
|
253 number of participants
n=4 Participants
|
|
Race/Ethnicity, Customized
Not Hispanic or Latino
|
157 number of participants
n=5 Participants
|
155 number of participants
n=7 Participants
|
142 number of participants
n=5 Participants
|
454 number of participants
n=4 Participants
|
PRIMARY outcome
Timeframe: Baseline up to week 12Population: Modified intent to treat (mITT) population which included all participants included in the ITT population (included all randomized participants that received the study treatment \& had at least one post-baseline efficacy assessment), except participants randomized in a site where good clinical practice issues were identified.
The WOMAC Osteoarthritis Index is a 24-item questionnaire that assesses pain, physical function, and stiffness in the target joint. WOMAC Pain was measured using visual analogue scale (VAS) ranging from 0mm (no pain) to 100mm (extreme pain) at baseline and at week 1, 2, 4, 8, and 12. Lower values represent a better outcome. At each time point the assessment included 5 WOMAC Pain items: 1-walking on flat, 2-going up down stairs, 3-at night while in bed, 4-sitting or lying; 5-standing upright. Mean WOMAC Pain subscale score was calculated at each visit as the sum of 5 pain category scores divided by 5. Change from baseline was calculated for each visit as the mean WOMAC Pain subscale score minus the mean baseline WOMAC Pain subscale score. A negative change from Baseline indicated improvement. The time-weighted mean change was calculated as the area under the curve of change from baseline divided by the nominal time of the last on-therapy visit (week 12) from randomization (baseline).
Outcome measures
| Measure |
Paracetamol 2000 mg Twice Daily (BID)
n=224 Participants
Participants were instructed to take two active paracetamol 1000 mg SR tablets twice daily (with 10-12 hours between adjacent doses) and two placebo to match paracetamol 665 mg SR tablets thrice daily (with 6-8 hours between adjacent doses) orally with approximately 8 ounces ( ̴240 mL) of water/dose for 12 weeks.
|
Paracetamol 1330 mg Thrice Daily (TID)
n=225 Participants
Participants were instructed to take two active paracetamol 665 mg SR tablets orally thrice daily (with 6-8 hours between adjacent doses) and two placebo to match paracetamol 1000 mg SR tablets orally twice daily (with 10-12 hours between adjacent doses) orally with approximately 8 ounces ( ̴240 mL) of water/dose for 12 weeks.
|
Placebo
n=227 Participants
Participants were instructed to take two placebo to match paracetamol 1000 mg SR tablets twice daily (with 10-12 hours between adjacent doses) and two placebo to match paracetamol 665 mg SR tablets thrice daily (with 6-8 hours between adjacent doses) orally with approximately 8 ounces ( ̴240 mL) of water/dose for 12 weeks.
|
|---|---|---|---|
|
Time-weighted Mean Change From Baseline in Western Ontario McMaster (WOMAC) Pain Through Week 12 of Treatment
|
-28.25 millimeter(mm)
Standard Error 1.697
|
-25.89 millimeter(mm)
Standard Error 1.714
|
-25.74 millimeter(mm)
Standard Error 1.713
|
SECONDARY outcome
Timeframe: Baseline up to Week 12Population: Analysis for this outcome was conducted on mITT population which included all participants included in the ITT population (included all randomized participants that received the study treatment \& had at least one post-baseline efficacy assessment), except participants randomized in a site where good clinical practices issues were identified.
The WOMAC Osteoarthritis Index is a 24-item questionnaire that assesses pain, physical function, and stiffness in the target joint. WOMAC Physical function was measured using VAS ranging from 0mm (no difficulty) to 100mm (extreme difficulty) at baseline and at week 1, 2, 4, 8, and 12. Lower values represent a better outcome. At each time point the assessment included 17 WOMAC Physical function categories. Mean WOMAC Physical function was calculated for baseline and each time point (sum of scores for 17 physical function categories divided by 17). Change from baseline was calculated for each visit as mean WOMAC physical function subscale score minus mean baseline WOMAC physical function subscale score. A negative change from Baseline indicated improvement. The time-weighted mean change was calculated as the area under the curve of change from baseline divided by the nominal time of the last on-therapy visit (week 12) from randomization (baseline).
Outcome measures
| Measure |
Paracetamol 2000 mg Twice Daily (BID)
n=224 Participants
Participants were instructed to take two active paracetamol 1000 mg SR tablets twice daily (with 10-12 hours between adjacent doses) and two placebo to match paracetamol 665 mg SR tablets thrice daily (with 6-8 hours between adjacent doses) orally with approximately 8 ounces ( ̴240 mL) of water/dose for 12 weeks.
|
Paracetamol 1330 mg Thrice Daily (TID)
n=225 Participants
Participants were instructed to take two active paracetamol 665 mg SR tablets orally thrice daily (with 6-8 hours between adjacent doses) and two placebo to match paracetamol 1000 mg SR tablets orally twice daily (with 10-12 hours between adjacent doses) orally with approximately 8 ounces ( ̴240 mL) of water/dose for 12 weeks.
|
Placebo
n=227 Participants
Participants were instructed to take two placebo to match paracetamol 1000 mg SR tablets twice daily (with 10-12 hours between adjacent doses) and two placebo to match paracetamol 665 mg SR tablets thrice daily (with 6-8 hours between adjacent doses) orally with approximately 8 ounces ( ̴240 mL) of water/dose for 12 weeks.
|
|---|---|---|---|
|
Time Weighted Mean Change From Baseline in WOMAC Physical Function Through Week 12 of Treatment
|
-28.24 mm
Standard Deviation 21.341
|
-26.23 mm
Standard Deviation 22.028
|
-26.68 mm
Standard Deviation 20.137
|
SECONDARY outcome
Timeframe: Baseline up to week 12Population: Analysis for this outcome was conducted on mITT population which included all participants included in the ITT population (included all randomized participants that received the study treatment \& had at least one post-baseline efficacy assessment), except participants randomized in a site where good clinical practices issues were identified.
The WOMAC Osteoarthritis Index is a 24-item questionnaire that assesses pain, physical function, and stiffness in the target joint. WOMAC stiffness was measured using VAS ranging from 0mm (no stiffness) to 100mm (maximum stiffness) at baseline and at week 1, 2, 4, 8, and 12. Lower values represent a better outcome. At each time point the assessment included 2 WOMAC stiffness categories: 1- after awakening in the morning; 2- later in the day. Mean WOMAC stiffness was calculated for baseline and each time point (sum of scores for 2 stiffness categories divided by 2). Change from baseline was calculated for each visit as mean WOMAC stiffness subscale score at specific time point minus mean WOMAC stiffness subscale score at baseline. A negative change from Baseline indicated improvement. The time-weighted mean change from baseline was calculated as area under the curve of change from baseline divided by nominal time of the last on-therapy visit (week 12) from randomization (baseline).
Outcome measures
| Measure |
Paracetamol 2000 mg Twice Daily (BID)
n=224 Participants
Participants were instructed to take two active paracetamol 1000 mg SR tablets twice daily (with 10-12 hours between adjacent doses) and two placebo to match paracetamol 665 mg SR tablets thrice daily (with 6-8 hours between adjacent doses) orally with approximately 8 ounces ( ̴240 mL) of water/dose for 12 weeks.
|
Paracetamol 1330 mg Thrice Daily (TID)
n=225 Participants
Participants were instructed to take two active paracetamol 665 mg SR tablets orally thrice daily (with 6-8 hours between adjacent doses) and two placebo to match paracetamol 1000 mg SR tablets orally twice daily (with 10-12 hours between adjacent doses) orally with approximately 8 ounces ( ̴240 mL) of water/dose for 12 weeks.
|
Placebo
n=227 Participants
Participants were instructed to take two placebo to match paracetamol 1000 mg SR tablets twice daily (with 10-12 hours between adjacent doses) and two placebo to match paracetamol 665 mg SR tablets thrice daily (with 6-8 hours between adjacent doses) orally with approximately 8 ounces ( ̴240 mL) of water/dose for 12 weeks.
|
|---|---|---|---|
|
Time Weighted Mean Change From Baseline in WOMAC Stiffness Through Week 12 of Treatment
|
-27.68 mm
Standard Deviation 21.579
|
-25.61 mm
Standard Deviation 22.238
|
-26.16 mm
Standard Deviation 21.554
|
SECONDARY outcome
Timeframe: Baseline up to week 12Population: Analysis for this outcome was conducted on mITT population which included all participants included in the ITT population (included all randomized participants that received the study treatment \& had at least one post-baseline efficacy assessment), except participants randomized in a site where good clinical practices issues were identified.
The WOMAC Osteoarthritis Index is a 24-item questionnaire that assesses pain, physical function, and stiffness in the target joint. The Total Index Score included the WOMAC Pain Score (5 questions about pain where: 0=no pain to 100=extreme pain), the WOMAC Physical Function score (17 questions about the difficulty of daily activities where: 0=no difficulty to 100=extreme difficulty) and the WOMAC Stiffness Score (2 questions about stiffness where: 0=no stiffness to 100=extreme stiffness). WOMAC Total Index was calculated at baseline and each time point as sum of scores of all 24 WOMAC questions divided by 2400, ranging from 0 (no pain/difficulty/stiffness) to 1 (extreme pain/ difficulty/stiffness). Change from baseline was calculated as WOMAC Total Index at specific time point minus WOMAC Total Index at baseline. A negative change from Baseline indicated improvement.
Outcome measures
| Measure |
Paracetamol 2000 mg Twice Daily (BID)
n=224 Participants
Participants were instructed to take two active paracetamol 1000 mg SR tablets twice daily (with 10-12 hours between adjacent doses) and two placebo to match paracetamol 665 mg SR tablets thrice daily (with 6-8 hours between adjacent doses) orally with approximately 8 ounces ( ̴240 mL) of water/dose for 12 weeks.
|
Paracetamol 1330 mg Thrice Daily (TID)
n=225 Participants
Participants were instructed to take two active paracetamol 665 mg SR tablets orally thrice daily (with 6-8 hours between adjacent doses) and two placebo to match paracetamol 1000 mg SR tablets orally twice daily (with 10-12 hours between adjacent doses) orally with approximately 8 ounces ( ̴240 mL) of water/dose for 12 weeks.
|
Placebo
n=227 Participants
Participants were instructed to take two placebo to match paracetamol 1000 mg SR tablets twice daily (with 10-12 hours between adjacent doses) and two placebo to match paracetamol 665 mg SR tablets thrice daily (with 6-8 hours between adjacent doses) orally with approximately 8 ounces ( ̴240 mL) of water/dose for 12 weeks.
|
|---|---|---|---|
|
Time-weighted Mean Change From Baseline in WOMAC Total Index Through Week 12 of Treatment
|
-0.28 mm
Standard Deviation 0.209
|
-0.26 mm
Standard Deviation 0.217
|
-0.27 mm
Standard Deviation 0.200
|
SECONDARY outcome
Timeframe: Baseline, Week 4, Week 8, Week 12Population: Analysis for this outcome was conducted on mITT population which included all participants included in the ITT population (included all randomized participants that received the study treatment \& had at least one post-baseline efficacy assessment), except participants randomized in a site where good clinical practice issues were identified.
Participants performed an instantaneous GPAOA via a 0-100mm VAS, ranging from 0 (best ever) to 100 (worst ever) with respect to "With respect to your arthritis condition, how would you describe yourself now?" GPAOA was calculated periodically during the 12 week treatment period.
Outcome measures
| Measure |
Paracetamol 2000 mg Twice Daily (BID)
n=224 Participants
Participants were instructed to take two active paracetamol 1000 mg SR tablets twice daily (with 10-12 hours between adjacent doses) and two placebo to match paracetamol 665 mg SR tablets thrice daily (with 6-8 hours between adjacent doses) orally with approximately 8 ounces ( ̴240 mL) of water/dose for 12 weeks.
|
Paracetamol 1330 mg Thrice Daily (TID)
n=225 Participants
Participants were instructed to take two active paracetamol 665 mg SR tablets orally thrice daily (with 6-8 hours between adjacent doses) and two placebo to match paracetamol 1000 mg SR tablets orally twice daily (with 10-12 hours between adjacent doses) orally with approximately 8 ounces ( ̴240 mL) of water/dose for 12 weeks.
|
Placebo
n=227 Participants
Participants were instructed to take two placebo to match paracetamol 1000 mg SR tablets twice daily (with 10-12 hours between adjacent doses) and two placebo to match paracetamol 665 mg SR tablets thrice daily (with 6-8 hours between adjacent doses) orally with approximately 8 ounces ( ̴240 mL) of water/dose for 12 weeks.
|
|---|---|---|---|
|
Mean Change From Baseline in Global Patient Assessment of Arthritis (GPAOA)
Change from baseline at Week 12
|
-36.15 mm
Standard Deviation 26.192
|
-33.04 mm
Standard Deviation 29.547
|
-34.31 mm
Standard Deviation 25.521
|
|
Mean Change From Baseline in Global Patient Assessment of Arthritis (GPAOA)
At Baseline
|
68.23 mm
Standard Deviation 16.965
|
69.20 mm
Standard Deviation 16.607
|
69.79 mm
Standard Deviation 16.734
|
|
Mean Change From Baseline in Global Patient Assessment of Arthritis (GPAOA)
At Week 4
|
39.34 mm
Standard Deviation 20.605
|
41.46 mm
Standard Deviation 22.330
|
42.93 mm
Standard Deviation 21.856
|
|
Mean Change From Baseline in Global Patient Assessment of Arthritis (GPAOA)
Change from baseline at Week 4
|
-29.02 mm
Standard Deviation 22.343
|
-27.78 mm
Standard Deviation 26.398
|
-26.83 mm
Standard Deviation 24.229
|
|
Mean Change From Baseline in Global Patient Assessment of Arthritis (GPAOA)
At Week 8
|
36.08 mm
Standard Deviation 22.662
|
37.62 mm
Standard Deviation 23.523
|
39.09 mm
Standard Deviation 21.858
|
|
Mean Change From Baseline in Global Patient Assessment of Arthritis (GPAOA)
Change from baseline at Week 8
|
-32.51 mm
Standard Deviation 24.429
|
-31.15 mm
Standard Deviation 28.064
|
-31.00 mm
Standard Deviation 23.649
|
|
Mean Change From Baseline in Global Patient Assessment of Arthritis (GPAOA)
At Week 12
|
32.41 mm
Standard Deviation 23.737
|
36.04 mm
Standard Deviation 23.848
|
35.44 mm
Standard Deviation 20.546
|
SECONDARY outcome
Timeframe: Baseline, Week 12Population: Analysis for this outcome was conducted on mITT population which included all participants included in the ITT population (included all randomized participants that received the study treatment \& had at least one post-baseline efficacy assessment), except participants randomized in a site where good clinical practice issues were identified.
A participant was considered a "responder" if his/her improvement from baseline (change from baseline at week 12) satisfied at least one of the two criteria high' or 'moderate' improvement as follows:- High improvement: 50% improvement from baseline in the last available WOMAC pain score or 60% improvement from baseline in the last available WOMAC physical function score. Moderate improvement: Fulfills two out of three criteria: 30% improvement from baseline in the last available WOMAC Pain score, 20% improvement from baseline in the last available WOMAC Physical Function score, 25% improvement from baseline in the last available GPAOA.
Outcome measures
| Measure |
Paracetamol 2000 mg Twice Daily (BID)
n=224 Participants
Participants were instructed to take two active paracetamol 1000 mg SR tablets twice daily (with 10-12 hours between adjacent doses) and two placebo to match paracetamol 665 mg SR tablets thrice daily (with 6-8 hours between adjacent doses) orally with approximately 8 ounces ( ̴240 mL) of water/dose for 12 weeks.
|
Paracetamol 1330 mg Thrice Daily (TID)
n=225 Participants
Participants were instructed to take two active paracetamol 665 mg SR tablets orally thrice daily (with 6-8 hours between adjacent doses) and two placebo to match paracetamol 1000 mg SR tablets orally twice daily (with 10-12 hours between adjacent doses) orally with approximately 8 ounces ( ̴240 mL) of water/dose for 12 weeks.
|
Placebo
n=227 Participants
Participants were instructed to take two placebo to match paracetamol 1000 mg SR tablets twice daily (with 10-12 hours between adjacent doses) and two placebo to match paracetamol 665 mg SR tablets thrice daily (with 6-8 hours between adjacent doses) orally with approximately 8 ounces ( ̴240 mL) of water/dose for 12 weeks.
|
|---|---|---|---|
|
Number of Participants Classified as Responder
|
157 participants
|
148 participants
|
159 participants
|
SECONDARY outcome
Timeframe: Baseline, Week 12Population: Analysis for this outcome was conducted on mITT population which included all participants included in the ITT population (included all randomized participants that received the study treatment \& had at least one post-baseline efficacy assessment), except participants randomized in a site where good clinical practices issues were identified.
Participants assessed their daily pain and stiffness each morning (upon awakening) during the 12-week treatment period using an 11-point Numerical Rating Scale (NRS), ranging from 0 (no pain / no stiffness) to 10 (extreme pain / extreme stiffness). Composite daily pain/stiffness score was calculated as sum of scores of pain and stiffness each morning divided by 2, ranging from 0 (no pain/stiffness) to 10 (extreme pain/stiffness). The mean of pain, mean of stiffness, and mean pain /stiffness composite score was calculated. Change from baseline was calculated as the difference between Daily Pain, stiffness and composite score each morning with that at baseline and was presented per week. A negative change from Baseline indicated improvement.
Outcome measures
| Measure |
Paracetamol 2000 mg Twice Daily (BID)
n=224 Participants
Participants were instructed to take two active paracetamol 1000 mg SR tablets twice daily (with 10-12 hours between adjacent doses) and two placebo to match paracetamol 665 mg SR tablets thrice daily (with 6-8 hours between adjacent doses) orally with approximately 8 ounces ( ̴240 mL) of water/dose for 12 weeks.
|
Paracetamol 1330 mg Thrice Daily (TID)
n=225 Participants
Participants were instructed to take two active paracetamol 665 mg SR tablets orally thrice daily (with 6-8 hours between adjacent doses) and two placebo to match paracetamol 1000 mg SR tablets orally twice daily (with 10-12 hours between adjacent doses) orally with approximately 8 ounces ( ̴240 mL) of water/dose for 12 weeks.
|
Placebo
n=227 Participants
Participants were instructed to take two placebo to match paracetamol 1000 mg SR tablets twice daily (with 10-12 hours between adjacent doses) and two placebo to match paracetamol 665 mg SR tablets thrice daily (with 6-8 hours between adjacent doses) orally with approximately 8 ounces ( ̴240 mL) of water/dose for 12 weeks.
|
|---|---|---|---|
|
Mean Change From Baseline in Daily Pain, Daily Stiffness and Pain/Stiffness (Composite) at Week 12
Pain at Baseline (n= 224, 225, 227)
|
6.39 score on a scale
Standard Deviation 1.902
|
6.27 score on a scale
Standard Deviation 1.942
|
6.63 score on a scale
Standard Deviation 1.774
|
|
Mean Change From Baseline in Daily Pain, Daily Stiffness and Pain/Stiffness (Composite) at Week 12
Pain at Week 12(n= 176, 175, 177)
|
3.80 score on a scale
Standard Deviation 2.454
|
3.80 score on a scale
Standard Deviation 2.197
|
3.82 score on a scale
Standard Deviation 2.056
|
|
Mean Change From Baseline in Daily Pain, Daily Stiffness and Pain/Stiffness (Composite) at Week 12
Pain, Change at Week 12 (n= 176, 175, 177)
|
-2.54 score on a scale
Standard Deviation 2.301
|
-2.49 score on a scale
Standard Deviation 2.457
|
-2.91 score on a scale
Standard Deviation 2.442
|
|
Mean Change From Baseline in Daily Pain, Daily Stiffness and Pain/Stiffness (Composite) at Week 12
Stiffness at Baseline (n= 224, 225, 227)
|
6.20 score on a scale
Standard Deviation 2.015
|
6.13 score on a scale
Standard Deviation 1.908
|
6.38 score on a scale
Standard Deviation 1.842
|
|
Mean Change From Baseline in Daily Pain, Daily Stiffness and Pain/Stiffness (Composite) at Week 12
Stiffness at Week 12(n= 176, 175, 177)
|
3.56 score on a scale
Standard Deviation 2.383
|
3.63 score on a scale
Standard Deviation 2.246
|
3.72 score on a scale
Standard Deviation 2.145
|
|
Mean Change From Baseline in Daily Pain, Daily Stiffness and Pain/Stiffness (Composite) at Week 12
Stiffness, Change at Week 12(n= 176, 175, 177
|
-2.56 score on a scale
Standard Deviation 2.227
|
-2.44 score on a scale
Standard Deviation 2.361
|
-2.76 score on a scale
Standard Deviation 2.500
|
|
Mean Change From Baseline in Daily Pain, Daily Stiffness and Pain/Stiffness (Composite) at Week 12
Composite at Baseline (n= 224, 225, 227)
|
6.30 score on a scale
Standard Deviation 1.883
|
6.20 score on a scale
Standard Deviation 1.817
|
6.51 score on a scale
Standard Deviation 1.729
|
|
Mean Change From Baseline in Daily Pain, Daily Stiffness and Pain/Stiffness (Composite) at Week 12
Composite at Week 12(n= 176, 175, 177)
|
3.68 score on a scale
Standard Deviation 2.361
|
3.71 score on a scale
Standard Deviation 2.150
|
3.77 score on a scale
Standard Deviation 2.043
|
|
Mean Change From Baseline in Daily Pain, Daily Stiffness and Pain/Stiffness (Composite) at Week 12
Composite, Change at Week 12(n= 176, 175, 177
|
-2.55 score on a scale
Standard Deviation 2.209
|
-2.46 score on a scale
Standard Deviation 2.347
|
-2.83 score on a scale
Standard Deviation 2.410
|
SECONDARY outcome
Timeframe: every day up to 12 weeksPopulation: Analysis for this outcome was conducted on mITT population which included all participants included in the ITT population (included all randomized participants that received the study treatment \& had at least one post-baseline efficacy assessment), except participant randomized in a site where good clinical practice issues were identified.
Participants recorded use of rescue medication daily in their patient diary. The mean number of doses of rescue medications taken per day during the 12-week treatment period was calculated.
Outcome measures
| Measure |
Paracetamol 2000 mg Twice Daily (BID)
n=224 Participants
Participants were instructed to take two active paracetamol 1000 mg SR tablets twice daily (with 10-12 hours between adjacent doses) and two placebo to match paracetamol 665 mg SR tablets thrice daily (with 6-8 hours between adjacent doses) orally with approximately 8 ounces ( ̴240 mL) of water/dose for 12 weeks.
|
Paracetamol 1330 mg Thrice Daily (TID)
n=225 Participants
Participants were instructed to take two active paracetamol 665 mg SR tablets orally thrice daily (with 6-8 hours between adjacent doses) and two placebo to match paracetamol 1000 mg SR tablets orally twice daily (with 10-12 hours between adjacent doses) orally with approximately 8 ounces ( ̴240 mL) of water/dose for 12 weeks.
|
Placebo
n=227 Participants
Participants were instructed to take two placebo to match paracetamol 1000 mg SR tablets twice daily (with 10-12 hours between adjacent doses) and two placebo to match paracetamol 665 mg SR tablets thrice daily (with 6-8 hours between adjacent doses) orally with approximately 8 ounces ( ̴240 mL) of water/dose for 12 weeks.
|
|---|---|---|---|
|
Mean Number of Rescue Medication Pills Taken Per Day up to 12 Weeks
|
0.356 number of rescue medication pills/day
Standard Deviation 1.7910
|
0.200 number of rescue medication pills/day
Standard Deviation 0.8052
|
0.337 number of rescue medication pills/day
Standard Deviation 1.1254
|
SECONDARY outcome
Timeframe: Baseline, Week 4, Week 8, Week 12Population: Analysis for this outcome was conducted on mITT population which included all participants included in the ITT population (included all randomized participants that received the study treatment \& had at least one post-baseline efficacy assessment), except participant randomized in a site where good clinical practice issues were identified.
Chronic Pain Sleep Inventory (CPSI) was assessed, based on the three questions: CPSI-1-'Trouble falling asleep': How often the participant had trouble falling asleep? , CPSI-3-'Awakening due to pain at night': How often the subject was awakened by pain during the night, CPSI-4- Awakening due to pain in the morning': How often the participant was awakened by pain in the morning? The participants responded to these questions via 0-100mm VAS, ranging from 0 (never) to 100 (always). Sleep problem index (SPI) was calculated as mean of these three CPSI questions, ranging from 0 (never affected by pain during sleep) to 100 (always affected by pain during sleep).
Outcome measures
| Measure |
Paracetamol 2000 mg Twice Daily (BID)
n=224 Participants
Participants were instructed to take two active paracetamol 1000 mg SR tablets twice daily (with 10-12 hours between adjacent doses) and two placebo to match paracetamol 665 mg SR tablets thrice daily (with 6-8 hours between adjacent doses) orally with approximately 8 ounces ( ̴240 mL) of water/dose for 12 weeks.
|
Paracetamol 1330 mg Thrice Daily (TID)
n=225 Participants
Participants were instructed to take two active paracetamol 665 mg SR tablets orally thrice daily (with 6-8 hours between adjacent doses) and two placebo to match paracetamol 1000 mg SR tablets orally twice daily (with 10-12 hours between adjacent doses) orally with approximately 8 ounces ( ̴240 mL) of water/dose for 12 weeks.
|
Placebo
n=227 Participants
Participants were instructed to take two placebo to match paracetamol 1000 mg SR tablets twice daily (with 10-12 hours between adjacent doses) and two placebo to match paracetamol 665 mg SR tablets thrice daily (with 6-8 hours between adjacent doses) orally with approximately 8 ounces ( ̴240 mL) of water/dose for 12 weeks.
|
|---|---|---|---|
|
Mean Change From Baseline in Chronic Pain Sleep Inventory (CPSI)
At Week 4, Sleep Problems Index
|
32.16 mm
Standard Deviation 24.845
|
28.96 mm
Standard Deviation 26.102
|
33.52 mm
Standard Deviation 24.004
|
|
Mean Change From Baseline in Chronic Pain Sleep Inventory (CPSI)
At Week 4, Change in Sleep Problems Index
|
-27.04 mm
Standard Deviation 23.458
|
-27.59 mm
Standard Deviation 26.860
|
-27.53 mm
Standard Deviation 24.930
|
|
Mean Change From Baseline in Chronic Pain Sleep Inventory (CPSI)
At Week 8, CPSI-1
|
30.53 mm
Standard Deviation 26.672
|
29.22 mm
Standard Deviation 26.468
|
30.84 mm
Standard Deviation 24.277
|
|
Mean Change From Baseline in Chronic Pain Sleep Inventory (CPSI)
At Week 8, Change in CPSI-1
|
-29.98 mm
Standard Deviation 26.601
|
-27.45 mm
Standard Deviation 28.842
|
-31.34 mm
Standard Deviation 25.290
|
|
Mean Change From Baseline in Chronic Pain Sleep Inventory (CPSI)
At Week 8, CPSI-3
|
30.25 mm
Standard Deviation 27.329
|
29.45 mm
Standard Deviation 27.286
|
29.71 mm
Standard Deviation 24.478
|
|
Mean Change From Baseline in Chronic Pain Sleep Inventory (CPSI)
At Week 8, Change at CPSI-3
|
-29.16 mm
Standard Deviation 27.321
|
-26.91 mm
Standard Deviation 28.210
|
-30.83 mm
Standard Deviation 25.892
|
|
Mean Change From Baseline in Chronic Pain Sleep Inventory (CPSI)
At Week 8, CPSI-4
|
30.33 mm
Standard Deviation 26.856
|
29.12 mm
Standard Deviation 27.444
|
31.02 mm
Standard Deviation 24.625
|
|
Mean Change From Baseline in Chronic Pain Sleep Inventory (CPSI)
At Week 8, Change at CPSI-4
|
-28.19 mm
Standard Deviation 27.359
|
-26.78 mm
Standard Deviation 29.961
|
-30.11 mm
Standard Deviation 25.874
|
|
Mean Change From Baseline in Chronic Pain Sleep Inventory (CPSI)
At Week 8, Sleep Problems Index
|
30.33 mm
Standard Deviation 26.206
|
29.20 mm
Standard Deviation 26.533
|
30.50 mm
Standard Deviation 23.868
|
|
Mean Change From Baseline in Chronic Pain Sleep Inventory (CPSI)
At Week 8, Change in Sleep Problems Index
|
-29.15 mm
Standard Deviation 25.838
|
-27.11 mm
Standard Deviation 27.784
|
-30.78 mm
Standard Deviation 24.315
|
|
Mean Change From Baseline in Chronic Pain Sleep Inventory (CPSI)
At Week 12, CPSI-1
|
26.73 mm
Standard Deviation 25.302
|
26.90 mm
Standard Deviation 25.288
|
27.64 mm
Standard Deviation 21.977
|
|
Mean Change From Baseline in Chronic Pain Sleep Inventory (CPSI)
At Week 12, Change in CPSI-1
|
-33.12 mm
Standard Deviation 27.859
|
-30.17 mm
Standard Deviation 30.532
|
-34.43 mm
Standard Deviation 25.975
|
|
Mean Change From Baseline in Chronic Pain Sleep Inventory (CPSI)
At Week 12, CPSI-3
|
26.95 mm
Standard Deviation 25.124
|
26.63 mm
Standard Deviation 25.684
|
27.42 mm
Standard Deviation 21.827
|
|
Mean Change From Baseline in Chronic Pain Sleep Inventory (CPSI)
At Week 12, Change in CPSI-3
|
-32.23 mm
Standard Deviation 29.228
|
-29.99 mm
Standard Deviation 29.859
|
-33.01 mm
Standard Deviation 27.116
|
|
Mean Change From Baseline in Chronic Pain Sleep Inventory (CPSI)
At Week 12, CPSI-4
|
27.26 mm
Standard Deviation 25.887
|
26.85 mm
Standard Deviation 25.812
|
27.79 mm
Standard Deviation 22.581
|
|
Mean Change From Baseline in Chronic Pain Sleep Inventory (CPSI)
At Week 12, Change in CPSI-4
|
-30.90 mm
Standard Deviation 29.052
|
-29.73 mm
Standard Deviation 30.967
|
-32.97 mm
Standard Deviation 27.357
|
|
Mean Change From Baseline in Chronic Pain Sleep Inventory (CPSI)
At Week 12, Sleep Problems Index
|
26.96 mm
Standard Deviation 24.709
|
26.72 mm
Standard Deviation 25.135
|
27.61 mm
Standard Deviation 21.593
|
|
Mean Change From Baseline in Chronic Pain Sleep Inventory (CPSI)
At Week 12, Change in Sleep Problems Index
|
-32.11 mm
Standard Deviation 27.489
|
-30.03 mm
Standard Deviation 29.275
|
-33.48 mm
Standard Deviation 25.485
|
|
Mean Change From Baseline in Chronic Pain Sleep Inventory (CPSI)
At Baseline, CPSI-1
|
60.40 mm
Standard Deviation 26.089
|
57.77 mm
Standard Deviation 27.705
|
61.30 mm
Standard Deviation 25.500
|
|
Mean Change From Baseline in Chronic Pain Sleep Inventory (CPSI)
At Baseline, CPSI-3
|
59.21 mm
Standard Deviation 26.980
|
57.19 mm
Standard Deviation 28.829
|
60.50 mm
Standard Deviation 25.532
|
|
Mean Change From Baseline in Chronic Pain Sleep Inventory (CPSI)
At Baseline, CPSI-4
|
58.49 mm
Standard Deviation 27.759
|
56.94 mm
Standard Deviation 28.834
|
61.30 mm
Standard Deviation 25.773
|
|
Mean Change From Baseline in Chronic Pain Sleep Inventory (CPSI)
At Baseline, Sleep Problems Index
|
59.36 mm
Standard Deviation 25.886
|
57.26 mm
Standard Deviation 27.384
|
61.04 mm
Standard Deviation 24.156
|
|
Mean Change From Baseline in Chronic Pain Sleep Inventory (CPSI)
At Week 4, CPSI-1
|
32.32 mm
Standard Deviation 25.396
|
29.23 mm
Standard Deviation 26.718
|
34.01 mm
Standard Deviation 24.701
|
|
Mean Change From Baseline in Chronic Pain Sleep Inventory (CPSI)
At Week 4, Change in CPSI-1
|
-27.87 mm
Standard Deviation 24.563
|
-27.61 mm
Standard Deviation 28.248
|
-27.44 mm
Standard Deviation 26.746
|
|
Mean Change From Baseline in Chronic Pain Sleep Inventory (CPSI)
At Week 4, CPSI-3
|
32.54 mm
Standard Deviation 26.437
|
28.94 mm
Standard Deviation 27.232
|
32.75 mm
Standard Deviation 24.833
|
|
Mean Change From Baseline in Chronic Pain Sleep Inventory (CPSI)
At Week 4, Change in CPSI-3
|
-26.63 mm
Standard Deviation 25.621
|
-27.51 mm
Standard Deviation 28.497
|
-27.69 mm
Standard Deviation 26.257
|
|
Mean Change From Baseline in Chronic Pain Sleep Inventory (CPSI)
At Week 4, CPSI-4
|
31.70 mm
Standard Deviation 25.667
|
28.85 mm
Standard Deviation 26.365
|
33.80 mm
Standard Deviation 25.749
|
|
Mean Change From Baseline in Chronic Pain Sleep Inventory (CPSI)
At Week 4, Change in CPSI-4
|
-26.55 mm
Standard Deviation 25.230
|
-27.52 mm
Standard Deviation 28.135
|
-27.47 mm
Standard Deviation 27.265
|
SECONDARY outcome
Timeframe: Week 4, Week 8, Week 12Population: Analysis for this outcome was conducted on mITT population which included all participants included in the ITT population (included all randomized participants that received the study treatment \& had at least one post-baseline efficacy assessment), except participants randomized in a site where good clinical practice issues were identified.
The PGART is a global assessment of the participant's response to therapy, was measured using on a 5 point Likert scale as follows: 0=None (no good at all, ineffective), 1= Poor (some effect, but unsatisfactory), 2= Fair (reasonable effect, but could be better), 3= Good (satisfactory effect with occasional episodes of pain and/or stiffness), 4= Excellent (ideal response, virtually pain-free). Mean PGART scores from 5 point Likert scale was calculated periodically (at Week 4, Week 8, Week 12) for the 12 week treatment period.
Outcome measures
| Measure |
Paracetamol 2000 mg Twice Daily (BID)
n=224 Participants
Participants were instructed to take two active paracetamol 1000 mg SR tablets twice daily (with 10-12 hours between adjacent doses) and two placebo to match paracetamol 665 mg SR tablets thrice daily (with 6-8 hours between adjacent doses) orally with approximately 8 ounces ( ̴240 mL) of water/dose for 12 weeks.
|
Paracetamol 1330 mg Thrice Daily (TID)
n=225 Participants
Participants were instructed to take two active paracetamol 665 mg SR tablets orally thrice daily (with 6-8 hours between adjacent doses) and two placebo to match paracetamol 1000 mg SR tablets orally twice daily (with 10-12 hours between adjacent doses) orally with approximately 8 ounces ( ̴240 mL) of water/dose for 12 weeks.
|
Placebo
n=227 Participants
Participants were instructed to take two placebo to match paracetamol 1000 mg SR tablets twice daily (with 10-12 hours between adjacent doses) and two placebo to match paracetamol 665 mg SR tablets thrice daily (with 6-8 hours between adjacent doses) orally with approximately 8 ounces ( ̴240 mL) of water/dose for 12 weeks.
|
|---|---|---|---|
|
Patient Global Assessment of Response to Therapy (PGART)
At Week 4 (n=197, 188, 202)
|
2.50 score on a scale
Standard Deviation 0.867
|
2.43 score on a scale
Standard Deviation 0.871
|
2.25 score on a scale
Standard Deviation 0.900
|
|
Patient Global Assessment of Response to Therapy (PGART)
At Week 8(n=196, 184, 192)
|
2.58 score on a scale
Standard Deviation 0.852
|
2.40 score on a scale
Standard Deviation 0.998
|
2.44 score on a scale
Standard Deviation 0.958
|
|
Patient Global Assessment of Response to Therapy (PGART)
At Week 12(n=189, 182, 181)
|
2.62 score on a scale
Standard Deviation 0.870
|
2.46 score on a scale
Standard Deviation 1.022
|
2.43 score on a scale
Standard Deviation 1.045
|
Adverse Events
Paracetamol 2000 mg Twice Daily (BID)
Serious events: 4 serious events
Other events: 67 other events
Deaths: 0 deaths
Paracetamol 1330 mg Thrice Daily (TID)
Serious events: 5 serious events
Other events: 69 other events
Deaths: 0 deaths
Placebo
Serious events: 0 serious events
Other events: 51 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Paracetamol 2000 mg Twice Daily (BID)
n=234 participants at risk
Participants were instructed to take two active paracetamol 1000 mg SR tablets twice daily (with 10-12 hours between adjacent doses) and two placebo to match paracetamol 665 mg SR tablets thrice daily (with 6-8 hours between adjacent doses) orally with approximately 8 ounces ( ̴240 mL) of water/dose for 12 weeks.
|
Paracetamol 1330 mg Thrice Daily (TID)
n=236 participants at risk
Participants were instructed to take two active paracetamol 665 mg SR tablets orally thrice daily (with 6-8 hours between adjacent doses) and two placebo to match paracetamol 1000 mg SR tablets orally twice daily (with 10-12 hours between adjacent doses) orally with approximately 8 ounces ( ̴240 mL) of water/dose for 12 weeks.
|
Placebo
n=237 participants at risk
Participants were instructed to take two placebo to match paracetamol 1000 mg SR tablets twice daily (with 10-12 hours between adjacent doses) and two placebo to match paracetamol 665 mg SR tablets thrice daily (with 6-8 hours between adjacent doses) orally with approximately 8 ounces ( ̴240 mL) of water/dose for 12 weeks.
|
|---|---|---|---|
|
General disorders
CHEST PAIN
|
0.43%
1/234 • throughout the study completion (up to 408 days)
|
0.00%
0/236 • throughout the study completion (up to 408 days)
|
0.00%
0/237 • throughout the study completion (up to 408 days)
|
|
Gastrointestinal disorders
ABDOMINAL PAIN
|
0.43%
1/234 • throughout the study completion (up to 408 days)
|
0.00%
0/236 • throughout the study completion (up to 408 days)
|
0.00%
0/237 • throughout the study completion (up to 408 days)
|
|
Metabolism and nutrition disorders
DEHYDRATION
|
0.43%
1/234 • throughout the study completion (up to 408 days)
|
0.00%
0/236 • throughout the study completion (up to 408 days)
|
0.00%
0/237 • throughout the study completion (up to 408 days)
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
COLON CANCER
|
0.43%
1/234 • throughout the study completion (up to 408 days)
|
0.00%
0/236 • throughout the study completion (up to 408 days)
|
0.00%
0/237 • throughout the study completion (up to 408 days)
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
OESOPHAGEAL CARCINOMA
|
0.00%
0/234 • throughout the study completion (up to 408 days)
|
0.42%
1/236 • throughout the study completion (up to 408 days)
|
0.00%
0/237 • throughout the study completion (up to 408 days)
|
|
Hepatobiliary disorders
CHOLELITHIASIS
|
0.00%
0/234 • throughout the study completion (up to 408 days)
|
0.42%
1/236 • throughout the study completion (up to 408 days)
|
0.00%
0/237 • throughout the study completion (up to 408 days)
|
|
Injury, poisoning and procedural complications
GUN SHOT WOUND
|
0.00%
0/234 • throughout the study completion (up to 408 days)
|
0.42%
1/236 • throughout the study completion (up to 408 days)
|
0.00%
0/237 • throughout the study completion (up to 408 days)
|
|
Injury, poisoning and procedural complications
MULTIPLE INJURIES
|
0.00%
0/234 • throughout the study completion (up to 408 days)
|
0.42%
1/236 • throughout the study completion (up to 408 days)
|
0.00%
0/237 • throughout the study completion (up to 408 days)
|
|
Nervous system disorders
CEREBROVASCULAR ACCIDENT
|
0.00%
0/234 • throughout the study completion (up to 408 days)
|
0.42%
1/236 • throughout the study completion (up to 408 days)
|
0.00%
0/237 • throughout the study completion (up to 408 days)
|
Other adverse events
| Measure |
Paracetamol 2000 mg Twice Daily (BID)
n=234 participants at risk
Participants were instructed to take two active paracetamol 1000 mg SR tablets twice daily (with 10-12 hours between adjacent doses) and two placebo to match paracetamol 665 mg SR tablets thrice daily (with 6-8 hours between adjacent doses) orally with approximately 8 ounces ( ̴240 mL) of water/dose for 12 weeks.
|
Paracetamol 1330 mg Thrice Daily (TID)
n=236 participants at risk
Participants were instructed to take two active paracetamol 665 mg SR tablets orally thrice daily (with 6-8 hours between adjacent doses) and two placebo to match paracetamol 1000 mg SR tablets orally twice daily (with 10-12 hours between adjacent doses) orally with approximately 8 ounces ( ̴240 mL) of water/dose for 12 weeks.
|
Placebo
n=237 participants at risk
Participants were instructed to take two placebo to match paracetamol 1000 mg SR tablets twice daily (with 10-12 hours between adjacent doses) and two placebo to match paracetamol 665 mg SR tablets thrice daily (with 6-8 hours between adjacent doses) orally with approximately 8 ounces ( ̴240 mL) of water/dose for 12 weeks.
|
|---|---|---|---|
|
Gastrointestinal disorders
NAUSEA
|
3.4%
8/234 • throughout the study completion (up to 408 days)
|
2.1%
5/236 • throughout the study completion (up to 408 days)
|
1.7%
4/237 • throughout the study completion (up to 408 days)
|
|
Gastrointestinal disorders
DIARRHOEA
|
2.6%
6/234 • throughout the study completion (up to 408 days)
|
3.0%
7/236 • throughout the study completion (up to 408 days)
|
0.84%
2/237 • throughout the study completion (up to 408 days)
|
|
Gastrointestinal disorders
FLATULENCE
|
1.7%
4/234 • throughout the study completion (up to 408 days)
|
0.00%
0/236 • throughout the study completion (up to 408 days)
|
0.42%
1/237 • throughout the study completion (up to 408 days)
|
|
Gastrointestinal disorders
DYSPEPSIA
|
1.3%
3/234 • throughout the study completion (up to 408 days)
|
1.3%
3/236 • throughout the study completion (up to 408 days)
|
0.00%
0/237 • throughout the study completion (up to 408 days)
|
|
Gastrointestinal disorders
ABDOMINAL DISCOMFORT
|
0.85%
2/234 • throughout the study completion (up to 408 days)
|
0.85%
2/236 • throughout the study completion (up to 408 days)
|
1.7%
4/237 • throughout the study completion (up to 408 days)
|
|
Gastrointestinal disorders
ABDOMINAL PAIN UPPER
|
0.85%
2/234 • throughout the study completion (up to 408 days)
|
0.00%
0/236 • throughout the study completion (up to 408 days)
|
0.00%
0/237 • throughout the study completion (up to 408 days)
|
|
Gastrointestinal disorders
DRY MOUTH
|
0.85%
2/234 • throughout the study completion (up to 408 days)
|
0.42%
1/236 • throughout the study completion (up to 408 days)
|
0.42%
1/237 • throughout the study completion (up to 408 days)
|
|
Gastrointestinal disorders
VOMITING
|
0.85%
2/234 • throughout the study completion (up to 408 days)
|
0.85%
2/236 • throughout the study completion (up to 408 days)
|
0.84%
2/237 • throughout the study completion (up to 408 days)
|
|
Gastrointestinal disorders
ABDOMINAL PAIN
|
0.43%
1/234 • throughout the study completion (up to 408 days)
|
0.42%
1/236 • throughout the study completion (up to 408 days)
|
0.00%
0/237 • throughout the study completion (up to 408 days)
|
|
Gastrointestinal disorders
ABDOMINAL PAIN LOWER
|
0.43%
1/234 • throughout the study completion (up to 408 days)
|
0.42%
1/236 • throughout the study completion (up to 408 days)
|
0.00%
0/237 • throughout the study completion (up to 408 days)
|
|
Gastrointestinal disorders
CONSTIPATION
|
0.43%
1/234 • throughout the study completion (up to 408 days)
|
2.5%
6/236 • throughout the study completion (up to 408 days)
|
0.84%
2/237 • throughout the study completion (up to 408 days)
|
|
Gastrointestinal disorders
DENTAL CARIES
|
0.43%
1/234 • throughout the study completion (up to 408 days)
|
0.00%
0/236 • throughout the study completion (up to 408 days)
|
0.00%
0/237 • throughout the study completion (up to 408 days)
|
|
Gastrointestinal disorders
HAEMATOCHEZIA
|
0.43%
1/234 • throughout the study completion (up to 408 days)
|
0.00%
0/236 • throughout the study completion (up to 408 days)
|
0.00%
0/237 • throughout the study completion (up to 408 days)
|
|
Gastrointestinal disorders
ODYNOPHAGIA
|
0.43%
1/234 • throughout the study completion (up to 408 days)
|
0.00%
0/236 • throughout the study completion (up to 408 days)
|
0.00%
0/237 • throughout the study completion (up to 408 days)
|
|
Gastrointestinal disorders
ABDOMINAL DISTENSION
|
0.00%
0/234 • throughout the study completion (up to 408 days)
|
0.85%
2/236 • throughout the study completion (up to 408 days)
|
0.00%
0/237 • throughout the study completion (up to 408 days)
|
|
Gastrointestinal disorders
FAECES DISCOLOURED
|
0.00%
0/234 • throughout the study completion (up to 408 days)
|
0.42%
1/236 • throughout the study completion (up to 408 days)
|
0.42%
1/237 • throughout the study completion (up to 408 days)
|
|
Gastrointestinal disorders
GASTROOESOPHAGEAL REFLUX DISEASE
|
0.00%
0/234 • throughout the study completion (up to 408 days)
|
0.00%
0/236 • throughout the study completion (up to 408 days)
|
0.42%
1/237 • throughout the study completion (up to 408 days)
|
|
Infections and infestations
GASTROENTERITIS
|
2.6%
6/234 • throughout the study completion (up to 408 days)
|
0.42%
1/236 • throughout the study completion (up to 408 days)
|
0.42%
1/237 • throughout the study completion (up to 408 days)
|
|
Infections and infestations
UPPER RESPIRATORY TRACT INFECTION
|
2.1%
5/234 • throughout the study completion (up to 408 days)
|
1.3%
3/236 • throughout the study completion (up to 408 days)
|
0.84%
2/237 • throughout the study completion (up to 408 days)
|
|
Infections and infestations
BRONCHITIS
|
0.43%
1/234 • throughout the study completion (up to 408 days)
|
0.42%
1/236 • throughout the study completion (up to 408 days)
|
0.42%
1/237 • throughout the study completion (up to 408 days)
|
|
Infections and infestations
CONJUNCTIVITIS
|
0.43%
1/234 • throughout the study completion (up to 408 days)
|
0.00%
0/236 • throughout the study completion (up to 408 days)
|
0.00%
0/237 • throughout the study completion (up to 408 days)
|
|
Infections and infestations
INFLUENZA
|
0.43%
1/234 • throughout the study completion (up to 408 days)
|
0.85%
2/236 • throughout the study completion (up to 408 days)
|
0.84%
2/237 • throughout the study completion (up to 408 days)
|
|
Infections and infestations
NASOPHARYNGITIS
|
0.43%
1/234 • throughout the study completion (up to 408 days)
|
1.3%
3/236 • throughout the study completion (up to 408 days)
|
0.84%
2/237 • throughout the study completion (up to 408 days)
|
|
Infections and infestations
SINUSITIS
|
0.43%
1/234 • throughout the study completion (up to 408 days)
|
0.42%
1/236 • throughout the study completion (up to 408 days)
|
1.7%
4/237 • throughout the study completion (up to 408 days)
|
|
Infections and infestations
ACUTE SINUSITIS
|
0.00%
0/234 • throughout the study completion (up to 408 days)
|
0.00%
0/236 • throughout the study completion (up to 408 days)
|
0.42%
1/237 • throughout the study completion (up to 408 days)
|
|
Infections and infestations
CELLULITIS
|
0.00%
0/234 • throughout the study completion (up to 408 days)
|
0.42%
1/236 • throughout the study completion (up to 408 days)
|
0.00%
0/237 • throughout the study completion (up to 408 days)
|
|
Infections and infestations
DIVERTICULITIS
|
0.00%
0/234 • throughout the study completion (up to 408 days)
|
0.00%
0/236 • throughout the study completion (up to 408 days)
|
0.42%
1/237 • throughout the study completion (up to 408 days)
|
|
Infections and infestations
FOLLICULITIS
|
0.00%
0/234 • throughout the study completion (up to 408 days)
|
0.42%
1/236 • throughout the study completion (up to 408 days)
|
0.00%
0/237 • throughout the study completion (up to 408 days)
|
|
Infections and infestations
FUNGAL INFECTION
|
0.00%
0/234 • throughout the study completion (up to 408 days)
|
0.42%
1/236 • throughout the study completion (up to 408 days)
|
0.00%
0/237 • throughout the study completion (up to 408 days)
|
|
Infections and infestations
GASTROENTERITIS VIRAL
|
0.00%
0/234 • throughout the study completion (up to 408 days)
|
0.85%
2/236 • throughout the study completion (up to 408 days)
|
0.42%
1/237 • throughout the study completion (up to 408 days)
|
|
Infections and infestations
LOWER RESPIRATORY TRACT INFECTION
|
0.00%
0/234 • throughout the study completion (up to 408 days)
|
0.00%
0/236 • throughout the study completion (up to 408 days)
|
0.42%
1/237 • throughout the study completion (up to 408 days)
|
|
Infections and infestations
PNEUMONIA
|
0.00%
0/234 • throughout the study completion (up to 408 days)
|
0.42%
1/236 • throughout the study completion (up to 408 days)
|
0.00%
0/237 • throughout the study completion (up to 408 days)
|
|
Infections and infestations
TOOTH ABSCESS
|
0.00%
0/234 • throughout the study completion (up to 408 days)
|
0.00%
0/236 • throughout the study completion (up to 408 days)
|
0.42%
1/237 • throughout the study completion (up to 408 days)
|
|
Infections and infestations
URINARY TRACT INFECTION
|
0.00%
0/234 • throughout the study completion (up to 408 days)
|
0.00%
0/236 • throughout the study completion (up to 408 days)
|
0.84%
2/237 • throughout the study completion (up to 408 days)
|
|
Infections and infestations
VIRAL UPPER RESPIRATORY TRACT INFECTION
|
0.00%
0/234 • throughout the study completion (up to 408 days)
|
0.42%
1/236 • throughout the study completion (up to 408 days)
|
0.00%
0/237 • throughout the study completion (up to 408 days)
|
|
Musculoskeletal and connective tissue disorders
BACK PAIN
|
0.85%
2/234 • throughout the study completion (up to 408 days)
|
1.3%
3/236 • throughout the study completion (up to 408 days)
|
0.42%
1/237 • throughout the study completion (up to 408 days)
|
|
Musculoskeletal and connective tissue disorders
PAIN IN EXTREMITY
|
1.3%
3/234 • throughout the study completion (up to 408 days)
|
0.00%
0/236 • throughout the study completion (up to 408 days)
|
0.42%
1/237 • throughout the study completion (up to 408 days)
|
|
Musculoskeletal and connective tissue disorders
MUSCLE SPASMS
|
0.85%
2/234 • throughout the study completion (up to 408 days)
|
0.00%
0/236 • throughout the study completion (up to 408 days)
|
0.42%
1/237 • throughout the study completion (up to 408 days)
|
|
Musculoskeletal and connective tissue disorders
MYALGIA
|
0.85%
2/234 • throughout the study completion (up to 408 days)
|
0.00%
0/236 • throughout the study completion (up to 408 days)
|
0.00%
0/237 • throughout the study completion (up to 408 days)
|
|
Musculoskeletal and connective tissue disorders
ARTHRALGIA
|
0.43%
1/234 • throughout the study completion (up to 408 days)
|
1.3%
3/236 • throughout the study completion (up to 408 days)
|
0.42%
1/237 • throughout the study completion (up to 408 days)
|
|
Musculoskeletal and connective tissue disorders
JOINT SWELLING
|
0.43%
1/234 • throughout the study completion (up to 408 days)
|
0.42%
1/236 • throughout the study completion (up to 408 days)
|
0.00%
0/237 • throughout the study completion (up to 408 days)
|
|
Musculoskeletal and connective tissue disorders
MUSCULOSKELETAL CHEST PAIN
|
0.43%
1/234 • throughout the study completion (up to 408 days)
|
0.00%
0/236 • throughout the study completion (up to 408 days)
|
0.00%
0/237 • throughout the study completion (up to 408 days)
|
|
Musculoskeletal and connective tissue disorders
MUSCULOSKELETAL PAIN
|
0.43%
1/234 • throughout the study completion (up to 408 days)
|
0.00%
0/236 • throughout the study completion (up to 408 days)
|
0.84%
2/237 • throughout the study completion (up to 408 days)
|
|
Musculoskeletal and connective tissue disorders
TENDONITIS
|
0.43%
1/234 • throughout the study completion (up to 408 days)
|
0.85%
2/236 • throughout the study completion (up to 408 days)
|
0.00%
0/237 • throughout the study completion (up to 408 days)
|
|
Musculoskeletal and connective tissue disorders
JOINT STIFFNESS
|
0.00%
0/234 • throughout the study completion (up to 408 days)
|
0.00%
0/236 • throughout the study completion (up to 408 days)
|
0.42%
1/237 • throughout the study completion (up to 408 days)
|
|
Musculoskeletal and connective tissue disorders
OSTEOARTHRITIS
|
0.00%
0/234 • throughout the study completion (up to 408 days)
|
0.42%
1/236 • throughout the study completion (up to 408 days)
|
0.00%
0/237 • throughout the study completion (up to 408 days)
|
|
Nervous system disorders
HEADACHE
|
2.1%
5/234 • throughout the study completion (up to 408 days)
|
2.1%
5/236 • throughout the study completion (up to 408 days)
|
2.1%
5/237 • throughout the study completion (up to 408 days)
|
|
Nervous system disorders
DIZZINESS
|
1.3%
3/234 • throughout the study completion (up to 408 days)
|
1.3%
3/236 • throughout the study completion (up to 408 days)
|
0.42%
1/237 • throughout the study completion (up to 408 days)
|
|
Nervous system disorders
TENSION HEADACHE
|
0.85%
2/234 • throughout the study completion (up to 408 days)
|
0.00%
0/236 • throughout the study completion (up to 408 days)
|
0.00%
0/237 • throughout the study completion (up to 408 days)
|
|
Nervous system disorders
CEREBROVASCULAR ACCIDENT
|
0.00%
0/234 • throughout the study completion (up to 408 days)
|
0.42%
1/236 • throughout the study completion (up to 408 days)
|
0.00%
0/237 • throughout the study completion (up to 408 days)
|
|
Nervous system disorders
DYSGEUSIA
|
0.00%
0/234 • throughout the study completion (up to 408 days)
|
0.00%
0/236 • throughout the study completion (up to 408 days)
|
0.42%
1/237 • throughout the study completion (up to 408 days)
|
|
Nervous system disorders
PARAESTHESIA
|
0.00%
0/234 • throughout the study completion (up to 408 days)
|
0.00%
0/236 • throughout the study completion (up to 408 days)
|
0.42%
1/237 • throughout the study completion (up to 408 days)
|
|
General disorders
FATIGUE
|
1.3%
3/234 • throughout the study completion (up to 408 days)
|
0.00%
0/236 • throughout the study completion (up to 408 days)
|
0.84%
2/237 • throughout the study completion (up to 408 days)
|
|
General disorders
ASTHENIA
|
0.43%
1/234 • throughout the study completion (up to 408 days)
|
0.00%
0/236 • throughout the study completion (up to 408 days)
|
0.00%
0/237 • throughout the study completion (up to 408 days)
|
|
General disorders
CHEST PAIN
|
0.43%
1/234 • throughout the study completion (up to 408 days)
|
0.00%
0/236 • throughout the study completion (up to 408 days)
|
0.00%
0/237 • throughout the study completion (up to 408 days)
|
|
General disorders
CHILLS
|
0.43%
1/234 • throughout the study completion (up to 408 days)
|
0.00%
0/236 • throughout the study completion (up to 408 days)
|
0.00%
0/237 • throughout the study completion (up to 408 days)
|
|
General disorders
OEDEMA PERIPHERAL
|
0.43%
1/234 • throughout the study completion (up to 408 days)
|
0.42%
1/236 • throughout the study completion (up to 408 days)
|
0.84%
2/237 • throughout the study completion (up to 408 days)
|
|
General disorders
PERIPHERAL SWELLING
|
0.43%
1/234 • throughout the study completion (up to 408 days)
|
0.00%
0/236 • throughout the study completion (up to 408 days)
|
0.42%
1/237 • throughout the study completion (up to 408 days)
|
|
General disorders
INFLUENZA LIKE ILLNESS
|
0.00%
0/234 • throughout the study completion (up to 408 days)
|
0.00%
0/236 • throughout the study completion (up to 408 days)
|
0.42%
1/237 • throughout the study completion (up to 408 days)
|
|
General disorders
PYREXIA
|
0.00%
0/234 • throughout the study completion (up to 408 days)
|
0.42%
1/236 • throughout the study completion (up to 408 days)
|
0.00%
0/237 • throughout the study completion (up to 408 days)
|
|
Investigations
ALANINE AMINOTRANSFERASE INCREASED
|
3.0%
7/234 • throughout the study completion (up to 408 days)
|
1.7%
4/236 • throughout the study completion (up to 408 days)
|
0.00%
0/237 • throughout the study completion (up to 408 days)
|
|
Investigations
PROSTATIC SPECIFIC ANTIGEN INCREASED
|
0.43%
1/234 • throughout the study completion (up to 408 days)
|
0.00%
0/236 • throughout the study completion (up to 408 days)
|
0.00%
0/237 • throughout the study completion (up to 408 days)
|
|
Investigations
BLOOD PRESSURE INCREASED
|
0.00%
0/234 • throughout the study completion (up to 408 days)
|
0.42%
1/236 • throughout the study completion (up to 408 days)
|
0.42%
1/237 • throughout the study completion (up to 408 days)
|
|
Investigations
HEPATIC ENZYME INCREASED
|
0.00%
0/234 • throughout the study completion (up to 408 days)
|
1.3%
3/236 • throughout the study completion (up to 408 days)
|
0.00%
0/237 • throughout the study completion (up to 408 days)
|
|
Investigations
HEPATITIS C VIRUS TEST POSITIVE
|
0.00%
0/234 • throughout the study completion (up to 408 days)
|
0.00%
0/236 • throughout the study completion (up to 408 days)
|
0.42%
1/237 • throughout the study completion (up to 408 days)
|
|
Investigations
LIVER FUNCTION TEST INCREASED
|
0.00%
0/234 • throughout the study completion (up to 408 days)
|
0.42%
1/236 • throughout the study completion (up to 408 days)
|
0.00%
0/237 • throughout the study completion (up to 408 days)
|
|
Investigations
LYMPHOCYTE COUNT INCREASED
|
0.00%
0/234 • throughout the study completion (up to 408 days)
|
0.00%
0/236 • throughout the study completion (up to 408 days)
|
0.42%
1/237 • throughout the study completion (up to 408 days)
|
|
Investigations
WHITE BLOOD CELL COUNT INCREASED
|
0.00%
0/234 • throughout the study completion (up to 408 days)
|
0.00%
0/236 • throughout the study completion (up to 408 days)
|
0.42%
1/237 • throughout the study completion (up to 408 days)
|
|
Vascular disorders
HYPERTENSION
|
2.6%
6/234 • throughout the study completion (up to 408 days)
|
0.85%
2/236 • throughout the study completion (up to 408 days)
|
0.42%
1/237 • throughout the study completion (up to 408 days)
|
|
Vascular disorders
HOT FLUSH
|
0.43%
1/234 • throughout the study completion (up to 408 days)
|
0.00%
0/236 • throughout the study completion (up to 408 days)
|
0.00%
0/237 • throughout the study completion (up to 408 days)
|
|
Respiratory, thoracic and mediastinal disorders
OROPHARYNGEAL PAIN
|
0.85%
2/234 • throughout the study completion (up to 408 days)
|
0.85%
2/236 • throughout the study completion (up to 408 days)
|
0.00%
0/237 • throughout the study completion (up to 408 days)
|
|
Respiratory, thoracic and mediastinal disorders
DRY THROAT
|
0.43%
1/234 • throughout the study completion (up to 408 days)
|
0.00%
0/236 • throughout the study completion (up to 408 days)
|
0.00%
0/237 • throughout the study completion (up to 408 days)
|
|
Respiratory, thoracic and mediastinal disorders
DYSPNOEA
|
0.43%
1/234 • throughout the study completion (up to 408 days)
|
0.00%
0/236 • throughout the study completion (up to 408 days)
|
0.00%
0/237 • throughout the study completion (up to 408 days)
|
|
Respiratory, thoracic and mediastinal disorders
NASAL CONGESTION
|
0.43%
1/234 • throughout the study completion (up to 408 days)
|
0.00%
0/236 • throughout the study completion (up to 408 days)
|
0.00%
0/237 • throughout the study completion (up to 408 days)
|
|
Respiratory, thoracic and mediastinal disorders
SINUS CONGESTION
|
0.43%
1/234 • throughout the study completion (up to 408 days)
|
0.00%
0/236 • throughout the study completion (up to 408 days)
|
0.00%
0/237 • throughout the study completion (up to 408 days)
|
|
Respiratory, thoracic and mediastinal disorders
CHRONIC OBSTRUCTIVE PULMONARY DISEASE
|
0.00%
0/234 • throughout the study completion (up to 408 days)
|
0.00%
0/236 • throughout the study completion (up to 408 days)
|
0.42%
1/237 • throughout the study completion (up to 408 days)
|
|
Respiratory, thoracic and mediastinal disorders
COUGH
|
0.00%
0/234 • throughout the study completion (up to 408 days)
|
0.00%
0/236 • throughout the study completion (up to 408 days)
|
0.42%
1/237 • throughout the study completion (up to 408 days)
|
|
Respiratory, thoracic and mediastinal disorders
RHINORRHOEA
|
0.00%
0/234 • throughout the study completion (up to 408 days)
|
0.42%
1/236 • throughout the study completion (up to 408 days)
|
0.00%
0/237 • throughout the study completion (up to 408 days)
|
|
Injury, poisoning and procedural complications
CONTUSION
|
0.43%
1/234 • throughout the study completion (up to 408 days)
|
0.85%
2/236 • throughout the study completion (up to 408 days)
|
0.00%
0/237 • throughout the study completion (up to 408 days)
|
|
Injury, poisoning and procedural complications
ANIMAL BITE
|
0.43%
1/234 • throughout the study completion (up to 408 days)
|
0.42%
1/236 • throughout the study completion (up to 408 days)
|
0.00%
0/237 • throughout the study completion (up to 408 days)
|
|
Injury, poisoning and procedural complications
TENDON RUPTURE
|
0.43%
1/234 • throughout the study completion (up to 408 days)
|
0.00%
0/236 • throughout the study completion (up to 408 days)
|
0.00%
0/237 • throughout the study completion (up to 408 days)
|
|
Injury, poisoning and procedural complications
GUN SHOT WOUND
|
0.00%
0/234 • throughout the study completion (up to 408 days)
|
0.42%
1/236 • throughout the study completion (up to 408 days)
|
0.00%
0/237 • throughout the study completion (up to 408 days)
|
|
Injury, poisoning and procedural complications
JOINT INJURY
|
0.00%
0/234 • throughout the study completion (up to 408 days)
|
0.42%
1/236 • throughout the study completion (up to 408 days)
|
0.00%
0/237 • throughout the study completion (up to 408 days)
|
|
Injury, poisoning and procedural complications
LIGAMENT SPRAIN
|
0.00%
0/234 • throughout the study completion (up to 408 days)
|
0.42%
1/236 • throughout the study completion (up to 408 days)
|
0.00%
0/237 • throughout the study completion (up to 408 days)
|
|
Injury, poisoning and procedural complications
MULTIPLE INJURIES
|
0.00%
0/234 • throughout the study completion (up to 408 days)
|
0.42%
1/236 • throughout the study completion (up to 408 days)
|
0.00%
0/237 • throughout the study completion (up to 408 days)
|
|
Injury, poisoning and procedural complications
PATELLA FRACTURE
|
0.00%
0/234 • throughout the study completion (up to 408 days)
|
0.42%
1/236 • throughout the study completion (up to 408 days)
|
0.00%
0/237 • throughout the study completion (up to 408 days)
|
|
Injury, poisoning and procedural complications
RIB FRACTURE
|
0.00%
0/234 • throughout the study completion (up to 408 days)
|
0.42%
1/236 • throughout the study completion (up to 408 days)
|
0.00%
0/237 • throughout the study completion (up to 408 days)
|
|
Skin and subcutaneous tissue disorders
RASH
|
0.85%
2/234 • throughout the study completion (up to 408 days)
|
0.00%
0/236 • throughout the study completion (up to 408 days)
|
0.00%
0/237 • throughout the study completion (up to 408 days)
|
|
Skin and subcutaneous tissue disorders
PRURITUS
|
0.43%
1/234 • throughout the study completion (up to 408 days)
|
0.85%
2/236 • throughout the study completion (up to 408 days)
|
0.00%
0/237 • throughout the study completion (up to 408 days)
|
|
Skin and subcutaneous tissue disorders
URTICARIA
|
0.43%
1/234 • throughout the study completion (up to 408 days)
|
0.00%
0/236 • throughout the study completion (up to 408 days)
|
0.00%
0/237 • throughout the study completion (up to 408 days)
|
|
Skin and subcutaneous tissue disorders
DIABETIC FOOT
|
0.00%
0/234 • throughout the study completion (up to 408 days)
|
0.00%
0/236 • throughout the study completion (up to 408 days)
|
0.42%
1/237 • throughout the study completion (up to 408 days)
|
|
Skin and subcutaneous tissue disorders
MILIARIA
|
0.00%
0/234 • throughout the study completion (up to 408 days)
|
0.00%
0/236 • throughout the study completion (up to 408 days)
|
0.42%
1/237 • throughout the study completion (up to 408 days)
|
|
Cardiac disorders
ARTERIOSCLEROSIS CORONARY ARTERY
|
0.43%
1/234 • throughout the study completion (up to 408 days)
|
0.00%
0/236 • throughout the study completion (up to 408 days)
|
0.00%
0/237 • throughout the study completion (up to 408 days)
|
|
Cardiac disorders
CORONARY ARTERY DISEASE
|
0.43%
1/234 • throughout the study completion (up to 408 days)
|
0.00%
0/236 • throughout the study completion (up to 408 days)
|
0.00%
0/237 • throughout the study completion (up to 408 days)
|
|
Cardiac disorders
CORONARY ARTERY STENOSIS
|
0.43%
1/234 • throughout the study completion (up to 408 days)
|
0.00%
0/236 • throughout the study completion (up to 408 days)
|
0.00%
0/237 • throughout the study completion (up to 408 days)
|
|
Renal and urinary disorders
NEPHROLITHIASIS
|
0.43%
1/234 • throughout the study completion (up to 408 days)
|
0.00%
0/236 • throughout the study completion (up to 408 days)
|
0.00%
0/237 • throughout the study completion (up to 408 days)
|
|
Renal and urinary disorders
RENAL FAILURE
|
0.43%
1/234 • throughout the study completion (up to 408 days)
|
0.00%
0/236 • throughout the study completion (up to 408 days)
|
0.00%
0/237 • throughout the study completion (up to 408 days)
|
|
Renal and urinary disorders
URINE FLOW DECREASED
|
0.43%
1/234 • throughout the study completion (up to 408 days)
|
0.00%
0/236 • throughout the study completion (up to 408 days)
|
0.00%
0/237 • throughout the study completion (up to 408 days)
|
|
Renal and urinary disorders
POLLAKIURIA
|
0.00%
0/234 • throughout the study completion (up to 408 days)
|
0.85%
2/236 • throughout the study completion (up to 408 days)
|
0.42%
1/237 • throughout the study completion (up to 408 days)
|
|
Renal and urinary disorders
RENAL PAIN
|
0.00%
0/234 • throughout the study completion (up to 408 days)
|
0.42%
1/236 • throughout the study completion (up to 408 days)
|
0.00%
0/237 • throughout the study completion (up to 408 days)
|
|
Renal and urinary disorders
URINARY INCONTINENCE
|
0.00%
0/234 • throughout the study completion (up to 408 days)
|
0.42%
1/236 • throughout the study completion (up to 408 days)
|
0.00%
0/237 • throughout the study completion (up to 408 days)
|
|
Renal and urinary disorders
URINARY RETENTION
|
0.00%
0/234 • throughout the study completion (up to 408 days)
|
0.42%
1/236 • throughout the study completion (up to 408 days)
|
0.00%
0/237 • throughout the study completion (up to 408 days)
|
|
Renal and urinary disorders
URINE ODOUR ABNORMAL
|
0.00%
0/234 • throughout the study completion (up to 408 days)
|
0.42%
1/236 • throughout the study completion (up to 408 days)
|
0.00%
0/237 • throughout the study completion (up to 408 days)
|
|
Ear and labyrinth disorders
TINNITUS
|
0.43%
1/234 • throughout the study completion (up to 408 days)
|
0.42%
1/236 • throughout the study completion (up to 408 days)
|
0.42%
1/237 • throughout the study completion (up to 408 days)
|
|
Ear and labyrinth disorders
VERTIGO
|
0.00%
0/234 • throughout the study completion (up to 408 days)
|
0.00%
0/236 • throughout the study completion (up to 408 days)
|
0.42%
1/237 • throughout the study completion (up to 408 days)
|
|
Eye disorders
DRY EYE
|
0.43%
1/234 • throughout the study completion (up to 408 days)
|
0.00%
0/236 • throughout the study completion (up to 408 days)
|
0.00%
0/237 • throughout the study completion (up to 408 days)
|
|
Immune system disorders
RUBBER SENSITIVITY
|
0.43%
1/234 • throughout the study completion (up to 408 days)
|
0.00%
0/236 • throughout the study completion (up to 408 days)
|
0.00%
0/237 • throughout the study completion (up to 408 days)
|
|
Metabolism and nutrition disorders
DEHYDRATION
|
0.43%
1/234 • throughout the study completion (up to 408 days)
|
0.00%
0/236 • throughout the study completion (up to 408 days)
|
0.00%
0/237 • throughout the study completion (up to 408 days)
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
COLON CANCER
|
0.43%
1/234 • throughout the study completion (up to 408 days)
|
0.00%
0/236 • throughout the study completion (up to 408 days)
|
0.00%
0/237 • throughout the study completion (up to 408 days)
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
OESOPHAGEAL CARCINOMA
|
0.00%
0/234 • throughout the study completion (up to 408 days)
|
0.42%
1/236 • throughout the study completion (up to 408 days)
|
0.00%
0/237 • throughout the study completion (up to 408 days)
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
UTERINE LEIOMYOMA
|
0.00%
0/234 • throughout the study completion (up to 408 days)
|
0.42%
1/236 • throughout the study completion (up to 408 days)
|
0.00%
0/237 • throughout the study completion (up to 408 days)
|
|
Psychiatric disorders
INSOMNIA
|
0.43%
1/234 • throughout the study completion (up to 408 days)
|
0.42%
1/236 • throughout the study completion (up to 408 days)
|
0.00%
0/237 • throughout the study completion (up to 408 days)
|
|
Blood and lymphatic system disorders
RED BLOOD CELL ABNORMALITY
|
0.00%
0/234 • throughout the study completion (up to 408 days)
|
0.42%
1/236 • throughout the study completion (up to 408 days)
|
0.00%
0/237 • throughout the study completion (up to 408 days)
|
|
Hepatobiliary disorders
CHOLELITHIASIS
|
0.00%
0/234 • throughout the study completion (up to 408 days)
|
0.42%
1/236 • throughout the study completion (up to 408 days)
|
0.00%
0/237 • throughout the study completion (up to 408 days)
|
|
Reproductive system and breast disorders
HYDROMETRA
|
0.00%
0/234 • throughout the study completion (up to 408 days)
|
0.42%
1/236 • throughout the study completion (up to 408 days)
|
0.00%
0/237 • throughout the study completion (up to 408 days)
|
|
Reproductive system and breast disorders
MENORRHAGIA
|
0.00%
0/234 • throughout the study completion (up to 408 days)
|
0.00%
0/236 • throughout the study completion (up to 408 days)
|
0.42%
1/237 • throughout the study completion (up to 408 days)
|
|
Reproductive system and breast disorders
PROSTATOMEGALY
|
0.00%
0/234 • throughout the study completion (up to 408 days)
|
0.42%
1/236 • throughout the study completion (up to 408 days)
|
0.00%
0/237 • throughout the study completion (up to 408 days)
|
|
Reproductive system and breast disorders
VULVOVAGINAL DRYNESS
|
0.00%
0/234 • throughout the study completion (up to 408 days)
|
0.00%
0/236 • throughout the study completion (up to 408 days)
|
0.42%
1/237 • throughout the study completion (up to 408 days)
|
Additional Information
GSK Response Center
GlaxoSmithKline
Phone: 866-435-7343
Results disclosure agreements
- Principal investigator is a sponsor employee GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
- Publication restrictions are in place
Restriction type: OTHER