Trial Outcomes & Findings for Efficacy And Safety Of Parecoxib 40mg vs. Ketoprofen 100mg In The Management Of Acute Renal Colic (NCT NCT00553605)

Last Updated: 2013-01-28

Results Overview

mPID score was obtained by summation of product of length of the interval and difference in pain intensity (PI) divided by summation of length of the interval. Summation was done from zero to 30 minutes. Difference in pain intensity was obtained by subtracting the Pain Intensity Visual Analogue Scale (PI-VAS) at Minute 30 from baseline PI-VAS score. PI-VAS assessed with response to the question "How much pain are you having right now?" on a 100 millimeter (mm) line, with 0 mm=no pain, 100 mm= worst possible pain. mPID score ranged from -100 to 100. Positive score= improved response in pain.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

340 participants

Primary outcome timeframe

Minute 30

Results posted on

2013-01-28

Participant Flow

Participant milestones

Participant milestones
Measure	Parecoxib Single dose of parecoxib 40 milligram (mg) solution intravenously by bolus injection followed by single dose of 100 milliliter (mL) solution of placebo matched to ketoprofen intravenously by slow injection over 20 minutes.	Ketoprofen Single bolus injection of 2 mL solution of placebo matched to parecoxib followed by single dose of ketoprofen 100 mg solution intravenously by slow injection over 20 minutes.
Overall Study STARTED	176	164
Overall Study Treated	174	164
Overall Study COMPLETED	172	161
Overall Study NOT COMPLETED	4	3

Reasons for withdrawal

Reasons for withdrawal
Measure	Parecoxib Single dose of parecoxib 40 milligram (mg) solution intravenously by bolus injection followed by single dose of 100 milliliter (mL) solution of placebo matched to ketoprofen intravenously by slow injection over 20 minutes.	Ketoprofen Single bolus injection of 2 mL solution of placebo matched to parecoxib followed by single dose of ketoprofen 100 mg solution intravenously by slow injection over 20 minutes.
Overall Study Did not meet entrance criteria	1	3
Overall Study Did not receive full dose	1	0
Overall Study Randomized but not treated	2	0

Baseline Characteristics

Efficacy And Safety Of Parecoxib 40mg vs. Ketoprofen 100mg In The Management Of Acute Renal Colic

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Parecoxib n=174 Participants Single dose of parecoxib 40 milligram (mg) solution intravenously by bolus injection followed by single dose of 100 milliliter (mL) solution of placebo matched to ketoprofen intravenously by slow injection over 20 minutes.	Ketoprofen n=164 Participants Single bolus injection of 2 mL solution of placebo matched to parecoxib followed by single dose of ketoprofen 100 mg solution intravenously by slow injection over 20 minutes.	Total n=338 Participants Total of all reporting groups
Age, Customized Less than (<) 18 years	1 participants n=5 Participants	0 participants n=7 Participants	1 participants n=5 Participants
Age, Customized 18 to 44 years	131 participants n=5 Participants	109 participants n=7 Participants	240 participants n=5 Participants
Age, Customized 45 to 64 years	41 participants n=5 Participants	54 participants n=7 Participants	95 participants n=5 Participants
Age, Customized Greater than or equal to (>=) 65 years	1 participants n=5 Participants	1 participants n=7 Participants	2 participants n=5 Participants
Sex: Female, Male Female	64 Participants n=5 Participants	61 Participants n=7 Participants	125 Participants n=5 Participants
Sex: Female, Male Male	110 Participants n=5 Participants	103 Participants n=7 Participants	213 Participants n=5 Participants

PRIMARY outcome

Timeframe: Minute 30

Population: Per-protocol (PP): all randomized participants who received at least 1 dose of study drug; had 1 post-baseline pain assessment; no major protocol violations; received appropriate dose of study drug; had valid baseline, 15 and 30 min VAS pain assessments; did not take rescue medications for 30 min; had confirmed diagnosis of nephrolithiasis.

Outcome measures

Outcome measures
Measure	Parecoxib n=156 Participants Single dose of parecoxib 40 milligram (mg) solution intravenously by bolus injection followed by single dose of 100 milliliter (mL) solution of placebo matched to ketoprofen intravenously by slow injection over 20 minutes.	Ketoprofen n=141 Participants Single bolus injection of 2 mL solution of placebo matched to parecoxib followed by single dose of ketoprofen 100 mg solution intravenously by slow injection over 20 minutes.
Mean Pain Intensity Difference at 30 Minutes (mPID30min)	34.147 mm Standard Error 3.35	35.266 mm Standard Error 3.46

SECONDARY outcome

Timeframe: Minute 120

Population: Modified intent- to-treat (mITT) included all randomized participants who received at least 1 dose of the study drug with at least 1 post-baseline pain assessment.

mPID score was obtained by summation of product of length of the interval and difference in pain intensity (PI) divided by summation of length of the interval. Summation was done from zero to 120 minutes. Difference in pain intensity was obtained by subtracting the Pain Intensity Visual Analogue Scale (PI-VAS) at Minute 120 from baseline PI-VAS score. PI-VAS assessed with response to the question "How much pain are you having right now?" on a 100 millimeter (mm) line, with 0 mm=no pain, 100 mm= worst possible pain. mPID score ranged from -100 to 100. Positive score= improved response in pain.

Outcome measures

Outcome measures
Measure	Parecoxib n=173 Participants Single dose of parecoxib 40 milligram (mg) solution intravenously by bolus injection followed by single dose of 100 milliliter (mL) solution of placebo matched to ketoprofen intravenously by slow injection over 20 minutes.	Ketoprofen n=164 Participants Single bolus injection of 2 mL solution of placebo matched to parecoxib followed by single dose of ketoprofen 100 mg solution intravenously by slow injection over 20 minutes.
Mean Pain Intensity Difference at 120 Min (mPID120min)	51.608 mm Standard Error 2.02	51.697 mm Standard Error 2.05

SECONDARY outcome

Timeframe: Baseline, Minute 15, 30, 45, 60, 90, 120

Population: mITT included all randomized participants who received at least 1 dose of the study drug with at least 1 post-baseline pain assessment. Here 'n' signifies participants who were evaluable at specific time point for each treatment arm respectively.

PI-VAS assessed with response to the question "How much pain are you having right now?" on a 100 mm line, with 0 mm=no pain, 100 mm= worst possible pain.

Outcome measures

Outcome measures
Measure	Parecoxib n=173 Participants Single dose of parecoxib 40 milligram (mg) solution intravenously by bolus injection followed by single dose of 100 milliliter (mL) solution of placebo matched to ketoprofen intravenously by slow injection over 20 minutes.	Ketoprofen n=164 Participants Single bolus injection of 2 mL solution of placebo matched to parecoxib followed by single dose of ketoprofen 100 mg solution intravenously by slow injection over 20 minutes.
Time-specific Pain Intensity (PI) VAS Score Baseline (n= 173, 164)	77.14 mm Standard Deviation 17.92	76.99 mm Standard Deviation 18.26
Time-specific Pain Intensity (PI) VAS Score Minute 15 (n= 173, 164)	50.42 mm Standard Deviation 26.92	50.95 mm Standard Deviation 24.65
Time-specific Pain Intensity (PI) VAS Score Minute 30 (n= 172, 162)	34.13 mm Standard Deviation 28.57	33.65 mm Standard Deviation 26.64
Time-specific Pain Intensity (PI) VAS Score Minute 45 (n= 163, 156)	21.75 mm Standard Deviation 24.89	23.15 mm Standard Deviation 24.93
Time-specific Pain Intensity (PI) VAS Score Minute 60 (n= 156, 152)	14.62 mm Standard Deviation 21.25	17.53 mm Standard Deviation 23.17
Time-specific Pain Intensity (PI) VAS Score Minute 90 (n= 151, 144)	9.80 mm Standard Deviation 17.16	12.27 mm Standard Deviation 20.22
Time-specific Pain Intensity (PI) VAS Score Minute 120 (n= 147, 139)	7.68 mm Standard Deviation 14.29	8.02 mm Standard Deviation 15.26

SECONDARY outcome

Timeframe: Baseline, Minute 15, 30, 45, 60, 90, 120

PID score was obtained by subtracting the PI-VAS at each time point from baseline PI score. PI-VAS assessed with response to the question "How much pain are you having right now?" on a 100 mm line, with 0 mm=no pain, 100 mm= worst possible pain. PID score ranged from -100 to 100. Positive score= improved response in pain.

Outcome measures

Outcome measures
Measure	Parecoxib n=173 Participants Single dose of parecoxib 40 milligram (mg) solution intravenously by bolus injection followed by single dose of 100 milliliter (mL) solution of placebo matched to ketoprofen intravenously by slow injection over 20 minutes.	Ketoprofen n=164 Participants Single bolus injection of 2 mL solution of placebo matched to parecoxib followed by single dose of ketoprofen 100 mg solution intravenously by slow injection over 20 minutes.
Time-specific Pain Intensity Difference (PID) at Minute 15, 30, 45, 60, 90 and 120 Minute 15 (n= 173, 164)	26.72 mm Standard Deviation 24.59	26.04 mm Standard Deviation 26.13
Time-specific Pain Intensity Difference (PID) at Minute 15, 30, 45, 60, 90 and 120 Minute 30 (n= 172, 162)	42.89 mm Standard Deviation 28.70	43.22 mm Standard Deviation 29.39
Time-specific Pain Intensity Difference (PID) at Minute 15, 30, 45, 60, 90 and 120 Minute 45 (n= 163, 156)	54.37 mm Standard Deviation 27.82	53.55 mm Standard Deviation 27.98
Time-specific Pain Intensity Difference (PID) at Minute 15, 30, 45, 60, 90 and 120 Minute 60 (n= 156, 152)	61.35 mm Standard Deviation 25.44	59.34 mm Standard Deviation 26.28
Time-specific Pain Intensity Difference (PID) at Minute 15, 30, 45, 60, 90 and 120 Minute 90 ( n= 151, 144)	65.99 mm Standard Deviation 22.88	64.33 mm Standard Deviation 25.05
Time-specific Pain Intensity Difference (PID) at Minute 15, 30, 45, 60, 90 and 120 Minute 120 (n= 147, 139)	68.07 mm Standard Deviation 21.14	68.51 mm Standard Deviation 21.21

SECONDARY outcome

Timeframe: Baseline through Minute 120

TOTPAR: time-weighted sum of Pain Relief (PR) over 120 min. TOTPAR score range was 0 (worst) to 480 (best). PR was assessed on a 5-point categorical pain relief rating scale wherein 0=No relief to 4=Complete relief.

Outcome measures

Outcome measures
Measure	Parecoxib n=171 Participants Single dose of parecoxib 40 milligram (mg) solution intravenously by bolus injection followed by single dose of 100 milliliter (mL) solution of placebo matched to ketoprofen intravenously by slow injection over 20 minutes.	Ketoprofen n=162 Participants Single bolus injection of 2 mL solution of placebo matched to parecoxib followed by single dose of ketoprofen 100 mg solution intravenously by slow injection over 20 minutes.
Time-weighted Sum of Pain Relief Score Over 120 Min (TOTPAR120min)	362.42 units on a scale Standard Error 10.65	352.29 units on a scale Standard Error 10.85

SECONDARY outcome

Timeframe: Minute 30, 120

Population: mITT included all randomized participants who received at least 1 dose of the study drug with at least 1 post-baseline pain assessment. Here 'N' (number of participants analyzed) signifies participants who were evaluable for this measure and 'n' signifies participants who were evaluable at specific time point for each treatment arm respectively.

PR was assessed on a 5-point categorical pain relief rating scale wherein 0= None, 1= a little, 2= Some, 3= a lot and 4= Complete relief.

Outcome measures

Outcome measures
Measure	Parecoxib n=171 Participants Single dose of parecoxib 40 milligram (mg) solution intravenously by bolus injection followed by single dose of 100 milliliter (mL) solution of placebo matched to ketoprofen intravenously by slow injection over 20 minutes.	Ketoprofen n=162 Participants Single bolus injection of 2 mL solution of placebo matched to parecoxib followed by single dose of ketoprofen 100 mg solution intravenously by slow injection over 20 minutes.
Number of Participants With Pain Relief (PR) Minute 30: none (n= 171, 162)	10 participants	9 participants
Number of Participants With Pain Relief (PR) Minute 30: a little (n= 171, 162)	21 participants	19 participants
Number of Participants With Pain Relief (PR) Minute 30: some (n= 171, 162)	35 participants	44 participants
Number of Participants With Pain Relief (PR) Minute 30: a lot (n= 171, 162)	74 participants	65 participants
Number of Participants With Pain Relief (PR) Minute 30: complete (n= 171, 162)	31 participants	25 participants
Number of Participants With Pain Relief (PR) Minute 120: none (n= 146, 139)	1 participants	1 participants
Number of Participants With Pain Relief (PR) Minute 120: a little (n= 146, 139)	0 participants	4 participants
Number of Participants With Pain Relief (PR) Minute 120: some (n= 146, 139)	16 participants	8 participants
Number of Participants With Pain Relief (PR) Minute 120: a lot (n= 146, 139)	40 participants	46 participants
Number of Participants With Pain Relief (PR) Minute 120: complete (n= 146, 139)	89 participants	80 participants

SECONDARY outcome

Timeframe: Minute 30

PI-VAS assessed with response to the question "How much pain are you having right now?" on a 100 mm line, with 0 mm=no pain, 100 mm= worst possible pain. Responders were those who had a decreased in VAS of at least 20 mm.

Outcome measures

Outcome measures
Measure	Parecoxib n=172 Participants Single dose of parecoxib 40 milligram (mg) solution intravenously by bolus injection followed by single dose of 100 milliliter (mL) solution of placebo matched to ketoprofen intravenously by slow injection over 20 minutes.	Ketoprofen n=162 Participants Single bolus injection of 2 mL solution of placebo matched to parecoxib followed by single dose of ketoprofen 100 mg solution intravenously by slow injection over 20 minutes.
Number of Participants With Response in Pain Intensity	132 participants	124 participants

SECONDARY outcome

Timeframe: Minute 30, 120

Participants' response to the question "How would you rate the study medication you received for pain?" on a 4-point categorical scale, 1=Poor, 2= Fair, 3=Good, 4=Excellent was evaluated.

Outcome measures

Outcome measures
Measure	Parecoxib n=172 Participants Single dose of parecoxib 40 milligram (mg) solution intravenously by bolus injection followed by single dose of 100 milliliter (mL) solution of placebo matched to ketoprofen intravenously by slow injection over 20 minutes.	Ketoprofen n=163 Participants Single bolus injection of 2 mL solution of placebo matched to parecoxib followed by single dose of ketoprofen 100 mg solution intravenously by slow injection over 20 minutes.
Patient's Global Evaluation of Study Medication Minute 30: poor	12 participants	10 participants
Patient's Global Evaluation of Study Medication Minute 30: fair	21 participants	17 participants
Patient's Global Evaluation of Study Medication Minute 30: good	76 participants	66 participants
Patient's Global Evaluation of Study Medication Minute 30: excellent	63 participants	70 participants
Patient's Global Evaluation of Study Medication Minute 120: poor	8 participants	5 participants
Patient's Global Evaluation of Study Medication Minute 120: fair	16 participants	16 participants
Patient's Global Evaluation of Study Medication Minute 120: good	49 participants	46 participants
Patient's Global Evaluation of Study Medication Minute 120: excellent	98 participants	96 participants

SECONDARY outcome

Timeframe: Minute 30, 120

Physicians' response to the question "How would you rate the study medication the patient received for pain?" on a 4-point categorical scale, 1=Poor, 2= Fair, 3=Good, 4=Excellent was evaluated.

Outcome measures

Outcome measures
Measure	Parecoxib n=172 Participants Single dose of parecoxib 40 milligram (mg) solution intravenously by bolus injection followed by single dose of 100 milliliter (mL) solution of placebo matched to ketoprofen intravenously by slow injection over 20 minutes.	Ketoprofen n=163 Participants Single bolus injection of 2 mL solution of placebo matched to parecoxib followed by single dose of ketoprofen 100 mg solution intravenously by slow injection over 20 minutes.
Physician's Global Evaluation of Study Medication Minute 30: poor	11 participants	11 participants
Physician's Global Evaluation of Study Medication Minute 30: fair	22 participants	23 participants
Physician's Global Evaluation of Study Medication Minute 30: good	69 participants	63 participants
Physician's Global Evaluation of Study Medication Minute 30: excellent	70 participants	66 participants
Physician's Global Evaluation of Study Medication Minute 120: poor	8 participants	8 participants
Physician's Global Evaluation of Study Medication Minute 120: fair	14 participants	15 participants
Physician's Global Evaluation of Study Medication Minute 120: good	45 participants	45 participants
Physician's Global Evaluation of Study Medication Minute 120: excellent	104 participants	95 participants

SECONDARY outcome

Timeframe: Up to Minute 120

Population: mITT included all randomized participants who received at least 1 dose of the study drug with at least 1 post-baseline pain assessment.

Rescue medications included intravenous 0.1 to 0.2 mg/kilogram (kg) of morphine or 1 mg/kg of pethidine or muscle relaxants.

Outcome measures

Outcome measures
Measure	Parecoxib n=173 Participants Single dose of parecoxib 40 milligram (mg) solution intravenously by bolus injection followed by single dose of 100 milliliter (mL) solution of placebo matched to ketoprofen intravenously by slow injection over 20 minutes.	Ketoprofen n=164 Participants Single bolus injection of 2 mL solution of placebo matched to parecoxib followed by single dose of ketoprofen 100 mg solution intravenously by slow injection over 20 minutes.
Number of Participants With Use of Rescue Medication (RM)	26 participants	25 participants

Adverse Events

Parecoxib

Serious events: 9 serious events

Other events: 47 other events

Deaths: 0 deaths

Ketoprofen

Serious events: 8 serious events

Other events: 55 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Parecoxib n=174 participants at risk Single dose of parecoxib 40 milligram (mg) solution intravenously by bolus injection followed by single dose of 100 milliliter (mL) solution of placebo matched to ketoprofen intravenously by slow injection over 20 minutes.	Ketoprofen n=164 participants at risk Single bolus injection of 2 mL solution of placebo matched to parecoxib followed by single dose of ketoprofen 100 mg solution intravenously by slow injection over 20 minutes.
Gastrointestinal disorders Abdominal pain	0.57% 1/174 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/164 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Colitis	0.57% 1/174 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/164 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
General disorders Condition aggravated	0.00% 0/174 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.61% 1/164 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Infections and infestations Urinary tract infection	0.57% 1/174 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/164 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Injury, poisoning and procedural complications Drug exposure during pregnancy	0.57% 1/174 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/164 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Renal and urinary disorders Calculus ureteric	0.57% 1/174 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/164 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Renal and urinary disorders Hydronephrosis	0.57% 1/174 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/164 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Renal and urinary disorders Renal colic	1.1% 2/174 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	4.3% 7/164 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Renal and urinary disorders Ureteric obstruction	0.57% 1/174 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/164 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.

Other adverse events

Additional Information

Pfizer ClinicalTrials.gov Call Center

Pfizer, Inc.

Phone: 1-800-718-1021

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
Publication restrictions are in place

Restriction type: OTHER

Measure	Parecoxib n=174 participants at risk Single dose of parecoxib 40 milligram (mg) solution intravenously by bolus injection followed by single dose of 100 milliliter (mL) solution of placebo matched to ketoprofen intravenously by slow injection over 20 minutes.	Ketoprofen n=164 participants at risk Single bolus injection of 2 mL solution of placebo matched to parecoxib followed by single dose of ketoprofen 100 mg solution intravenously by slow injection over 20 minutes.
Cardiac disorders Bradycardia	0.00% 0/174 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	1.2% 2/164 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Ear and labyrinth disorders Vertigo	0.00% 0/174 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.61% 1/164 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Abdominal pain	1.1% 2/174 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	2.4% 4/164 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Abdominal pain upper	0.00% 0/174 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.61% 1/164 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Constipation	0.00% 0/174 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.61% 1/164 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Diarrhoea	0.57% 1/174 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/164 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Flatulence	0.00% 0/174 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	2.4% 4/164 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Nausea	4.0% 7/174 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	3.0% 5/164 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Vomiting	2.3% 4/174 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	3.0% 5/164 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
General disorders Chills	0.57% 1/174 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	1.2% 2/164 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
General disorders Pain	3.4% 6/174 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	5.5% 9/164 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
General disorders Pyrexia	1.7% 3/174 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.61% 1/164 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
General disorders Vessel puncture site pain	0.00% 0/174 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.61% 1/164 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Infections and infestations Cystitis	0.00% 0/174 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.61% 1/164 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Infections and infestations Upper respiratory tract infection	0.00% 0/174 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.61% 1/164 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Metabolism and nutrition disorders Hyperglycaemia	0.00% 0/174 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.61% 1/164 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Musculoskeletal and connective tissue disorders Back pain	1.1% 2/174 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	1.8% 3/164 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Musculoskeletal and connective tissue disorders Myalgia	0.57% 1/174 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/164 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Nervous system disorders Dizziness	4.0% 7/174 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	1.2% 2/164 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Nervous system disorders Dizziness postural	0.57% 1/174 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/164 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Nervous system disorders Headache	1.7% 3/174 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	2.4% 4/164 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Nervous system disorders Paraesthesia	0.00% 0/174 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.61% 1/164 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Nervous system disorders Somnolence	0.00% 0/174 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.61% 1/164 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Renal and urinary disorders Dysuria	0.57% 1/174 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.61% 1/164 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Renal and urinary disorders Haematuria	0.57% 1/174 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.61% 1/164 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Renal and urinary disorders Renal colic	1.7% 3/174 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/164 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Renal and urinary disorders Renal pain	0.00% 0/174 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.61% 1/164 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Renal and urinary disorders Urethral pain	1.1% 2/174 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/164 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Skin and subcutaneous tissue disorders Pruritus	0.57% 1/174 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/164 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Vascular disorders Angiopathy	0.00% 0/174 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.61% 1/164 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Vascular disorders Hypotension	0.57% 1/174 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.61% 1/164 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.