ClinicalTrials.gov
ClinicalTrials.gov Menu

Cardiovascular Outcomes Study of Naltrexone SR/Bupropion SR in Overweight and Obese Subjects With Cardiovascular Risk Factors (The Light Study)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT01601704
Recruitment Status : Terminated
First Posted : May 18, 2012
Results First Posted : February 27, 2017
Last Update Posted : February 27, 2017
Sponsor:
Information provided by (Responsible Party):
Orexigen Therapeutics, Inc

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Conditions Obesity
Overweight
Interventions Drug: NB32
Drug: PBO
Behavioral: Weight Management Program
Enrollment 8910
Recruitment Details  
Pre-assignment Details  
Arm/Group Title NB32 Placebo
Hide Arm/Group Description

NB32: Naltrexone SR 32 mg/Bupropion SR 360 mg/day. Administered in addition to the weight management program.

Weight Management Program: A comprehensive weight management program will be administered in addition to the subject's study medication assignment. The program includes internet counseling by an accredited health and fitness professional and a nutrition and exercise program with goal setting and educational and tracking tools.

Administered in addition to the weight management program.

Weight Management Program: A comprehensive weight management program will be administered in addition to the subject's study medication assignment. The program includes internet counseling by an accredited health and fitness professional and a nutrition and exercise program with goal setting and educational and tracking tools.

Period Title: Overall Study
Started [1] 4456 4454
Treated [2] 4455 4450
Completed [3] 4455 4450
Not Completed 1 4
Reason Not Completed
Randomized but not dispensed study med             1             4
[1]
Represents number of participants randomized
[2]
Represents number of participants included in the ITT analysis
[3]
Completed indicates treated participants. Represents number of participants in the ITT analysis.
Arm/Group Title NB32 Placebo Total
Hide Arm/Group Description

NB32: Naltrexone SR 32 mg/Bupropion SR 360 mg/day. Administered in addition to the weight management program.

Weight Management Program: A comprehensive weight management program will be administered in addition to the subject's study medication assignment. The program includes internet counseling by an accredited health and fitness professional and a nutrition and exercise program with goal setting and educational and tracking tools.

Administered in addition to the weight management program.

Weight Management Program: A comprehensive weight management program will be administered in addition to the subject's study medication assignment. The program includes internet counseling by an accredited health and fitness professional and a nutrition and exercise program with goal setting and educational and tracking tools.

Total of all reporting groups
Overall Number of Baseline Participants 4455 4450 8905
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 4455 participants 4450 participants 8905 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
2973
  66.7%
3053
  68.6%
6026
  67.7%
>=65 years
1482
  33.3%
1397
  31.4%
2879
  32.3%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 4455 participants 4450 participants 8905 participants
61.1  (7.27) 60.9  (7.38) 61.0  (7.33)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 4455 participants 4450 participants 8905 participants
Female
2437
  54.7%
2419
  54.4%
4856
  54.5%
Male
2018
  45.3%
2031
  45.6%
4049
  45.5%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 4455 participants 4450 participants 8905 participants
Hispanic or Latino
279
   6.3%
291
   6.5%
570
   6.4%
Not Hispanic or Latino
4174
  93.7%
4156
  93.4%
8330
  93.5%
Unknown or Not Reported
2
   0.0%
3
   0.1%
5
   0.1%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 4455 participants 4450 participants 8905 participants
American Indian or Alaska Native
11
   0.2%
20
   0.4%
31
   0.3%
Asian
19
   0.4%
27
   0.6%
46
   0.5%
Native Hawaiian or Other Pacific Islander
6
   0.1%
6
   0.1%
12
   0.1%
Black or African American
656
  14.7%
648
  14.6%
1304
  14.6%
White
3738
  83.9%
3698
  83.1%
7436
  83.5%
More than one race NA [1]  NA [1]  NA [2] 
Unknown or Not Reported
25
   0.6%
51
   1.1%
76
   0.9%
[1]
Selection of multiple race categories was not permissible by the participants. Participants advised to select the most appropriate category.
[2]
Total not calculated because data are not available (NA) in one or more arms.
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
United States Number Analyzed 4455 participants 4450 participants 8905 participants
4455
 100.0%
4450
 100.0%
8905
 100.0%
Weight  
Mean (Standard Deviation)
Unit of measure:  Kilogram
Number Analyzed 4455 participants 4450 participants 8905 participants
105.6  (19.09) 106.3  (19.18) 106.0  (19.14)
Body Mass Index (BMI)   [1] 
Mean (Standard Deviation)
Unit of measure:  Kg/m^2
Number Analyzed 4452 participants 4450 participants 8902 participants
37.2  (5.26) 37.4  (5.44) 37.3  (5.35)
[1]
Measure Analysis Population Description: BMI was calculated at the site. Data are missing for 3 participants for whom the site did not calculate BMI, although weight and height were measured.
Cardiovascular (CV) risk group  
Measure Type: Count of Participants
Unit of measure:  Participants
CV disease without T2DM (type 2 diabetes mellitus) Number Analyzed 4455 participants 4450 participants 8905 participants
670
  15.0%
646
  14.5%
1316
  14.8%
CV disease with T2DM Number Analyzed 4455 participants 4450 participants 8905 participants
745
  16.7%
801
  18.0%
1546
  17.4%
T2DM without CV disease Number Analyzed 4455 participants 4450 participants 8905 participants
3039
  68.2%
3002
  67.5%
6041
  67.8%
Hypertension  
Measure Type: Count of Participants
Unit of measure:  Participants
Yes Number Analyzed 4455 participants 4450 participants 8905 participants
4162
  93.4%
4117
  92.5%
8279
  93.0%
No Number Analyzed 4455 participants 4450 participants 8905 participants
293
   6.6%
333
   7.5%
626
   7.0%
Dyslipidemia  
Measure Type: Count of Participants
Unit of measure:  Participants
Yes Number Analyzed 4455 participants 4450 participants 8905 participants
4100
  92.0%
4070
  91.5%
8170
  91.7%
No Number Analyzed 4455 participants 4450 participants 8905 participants
355
   8.0%
380
   8.5%
735
   8.3%
History of Depression  
Measure Type: Count of Participants
Unit of measure:  Participants
Yes Number Analyzed 4455 participants 4450 participants 8905 participants
1031
  23.1%
995
  22.4%
2026
  22.8%
No Number Analyzed 4455 participants 4450 participants 8905 participants
3424
  76.9%
3455
  77.6%
6879
  77.2%
Baseline Antidepressant Medication Use  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 4455 participants 4450 participants 8905 participants
1042
  23.4%
1015
  22.8%
2057
  23.1%
1.Primary Outcome
Title Percentage of Participants With a Confirmed Occurrence of Major Adverse Cardiovascular Event (MACE)
Hide Description The primary endpoint is the time from randomization to the first confirmed occurrence of any event within the primary MACE composite (defined as cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke). Due to early termination of the study, pre-planned 50% interim analysis is considered the primary analysis for outcome measures. The pre-planned 50% interim analysis was conducted when 50% of the total planned MACE were observed.
Time Frame Confirmed occurrence of event between Day 1 (randomization) and up to a maximum of 4 years of follow-up
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat (ITT) population is defined as subjects who undergo randomization into the Treatment Period (TP) and are dispensed study medication. Treatment refers to the treatment assigned during TP randomization rather than the actual treatment received. ITT population is the primary analysis population for the primary and secondary endpoints.
Arm/Group Title NB32 Placebo
Hide Arm/Group Description:

NB32: Naltrexone SR 32 mg/Bupropion SR 360 mg/day. Administered in addition to the weight management program.

Weight Management Program: A comprehensive weight management program will be administered in addition to the subject's study medication assignment. The program includes internet counseling by an accredited health and fitness professional and a nutrition and exercise program with goal setting and educational and tracking tools.

Administered in addition to the weight management program.

Weight Management Program: A comprehensive weight management program will be administered in addition to the subject's study medication assignment. The program includes internet counseling by an accredited health and fitness professional and a nutrition and exercise program with goal setting and educational and tracking tools.

Overall Number of Participants Analyzed 4455 4450
Measure Type: Count of Participants
Unit of Measure: Participants
90
   2.0%
102
   2.3%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection NB32, Placebo
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments At the pre-planned 50% interim analysis, a non-inferiority analysis was conducted based on the estimated hazard ratio (NB32/Placebo) for the time to the first confirmed occurrence of MACE. The upper-bound of the 99.7% confidence interval for the hazard ratio was compared to 1.4, the non-inferiority margin.
Method of Estimation Estimation Parameter Cox Proportional Hazard
Estimated Value 0.88
Confidence Interval (2-Sided) 99.7%
0.57 to 1.34
Estimation Comments Hazard ratio is based on CPH model with treatment as a factor.
2.Secondary Outcome
Title Percentage of Participants With a Confirmed Occurrence of Cardiovascular Death, Nonfatal Myocardial Infarction, Nonfatal Stroke, or Nonfatal Unstable Angina Requiring Hospitalization
Hide Description Due to early termination of the study, the pre-planned 50% interim analysis is considered the primary analysis for outcome measures.
Time Frame Confirmed occurrence of event between Day 1 (randomization) and up to a maximum of 4 years of follow-up
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat (ITT) population is defined as subjects who undergo randomization into the Treatment Period (TP) and are dispensed study medication. Treatment refers to the treatment assigned during TP randomization rather than the actual treatment received. ITT population is the primary analysis population for the primary and secondary endpoints.
Arm/Group Title NB32 Placebo
Hide Arm/Group Description:

NB32: Naltrexone SR 32 mg/Bupropion SR 360 mg/day. Administered in addition to the weight management program.

Weight Management Program: A comprehensive weight management program will be administered in addition to the subject's study medication assignment. The program includes internet counseling by an accredited health and fitness professional and a nutrition and exercise program with goal setting and educational and tracking tools.

Administered in addition to the weight management program.

Weight Management Program: A comprehensive weight management program will be administered in addition to the subject's study medication assignment. The program includes internet counseling by an accredited health and fitness professional and a nutrition and exercise program with goal setting and educational and tracking tools.

Overall Number of Participants Analyzed 4455 4450
Measure Type: Count of Participants
Unit of Measure: Participants
133
   3.0%
142
   3.2%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection NB32, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Cox Proportional Hazard
Estimated Value 0.93
Confidence Interval (2-Sided) 99.7%
0.66 to 1.33
Estimation Comments Hazard ratio is based on CPH model with treatment as a factor.
3.Secondary Outcome
Title Percentage of Participants With a Confirmed Occurrence of Cardiovascular Death (Including Fatal Myocardial Infarction, Fatal Stroke)
Hide Description Due to early termination of the study, the pre-planned 50% interim analysis is considered the primary analysis for outcome measures.
Time Frame Confirmed occurrence of event between Day 1 (randomization) and up to a maximum of 4 years of follow-up
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat (ITT) population is defined as subjects who undergo randomization into the Treatment Period (TP) and are dispensed study medication. Treatment refers to the treatment assigned during TP randomization rather than the actual treatment received. ITT population is the primary analysis population for the primary and secondary endpoints.
Arm/Group Title NB32 Placebo
Hide Arm/Group Description:

NB32: Naltrexone SR 32 mg/Bupropion SR 360 mg/day. Administered in addition to the weight management program.

Weight Management Program: A comprehensive weight management program will be administered in addition to the subject's study medication assignment. The program includes internet counseling by an accredited health and fitness professional and a nutrition and exercise program with goal setting and educational and tracking tools.

Administered in addition to the weight management program.

Weight Management Program: A comprehensive weight management program will be administered in addition to the subject's study medication assignment. The program includes internet counseling by an accredited health and fitness professional and a nutrition and exercise program with goal setting and educational and tracking tools.

Overall Number of Participants Analyzed 4455 4450
Measure Type: Count of Participants
Unit of Measure: Participants
17
   0.4%
34
   0.8%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection NB32, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Cox Proportional Hazard
Estimated Value 0.50
Confidence Interval (2-Sided) 99.7%
0.21 to 1.19
Estimation Comments Hazard ratio is based on CPH model with treatment as a factor.
4.Secondary Outcome
Title Percentage of Participants With a Confirmed Occurrence of Myocardial Infarction (Nonfatal or Fatal)
Hide Description Due to early termination of the study, the pre-planned 50% interim analysis is considered the primary analysis for outcome measures.
Time Frame Confirmed occurrence of event between Day 1 (randomization) and up to a maximum of 4 years of follow-up
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat (ITT) population is defined as subjects who undergo randomization into the Treatment Period (TP) and are dispensed study medication. Treatment refers to the treatment assigned during TP randomization rather than the actual treatment received. ITT population is the primary analysis population for the primary and secondary endpoints.
Arm/Group Title NB32 Placebo
Hide Arm/Group Description:

NB32: Naltrexone SR 32 mg/Bupropion SR 360 mg/day. Administered in addition to the weight management program.

Weight Management Program: A comprehensive weight management program will be administered in addition to the subject's study medication assignment. The program includes internet counseling by an accredited health and fitness professional and a nutrition and exercise program with goal setting and educational and tracking tools.

Administered in addition to the weight management program.

Weight Management Program: A comprehensive weight management program will be administered in addition to the subject's study medication assignment. The program includes internet counseling by an accredited health and fitness professional and a nutrition and exercise program with goal setting and educational and tracking tools.

Overall Number of Participants Analyzed 4455 4450
Measure Type: Count of Participants
Unit of Measure: Participants
55
   1.2%
57
   1.3%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection NB32, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Cox Proportional Hazard
Estimated Value 0.96
Confidence Interval (2-Sided) 99.7%
0.55 to 1.67
Estimation Comments Hazard ratio is based on CPH model with treatment as a factor.
5.Secondary Outcome
Title Percentage of Participants With a Confirmed Occurrence of Stroke (Nonfatal or Fatal)
Hide Description Due to early termination of the study, the pre-planned 50% interim analysis is considered the primary analysis for outcome measures.
Time Frame Confirmed occurrence of event between Day 1 (randomization) and up to a maximum of 4 years of follow-up
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat (ITT) population is defined as subjects who undergo randomization into the Treatment Period (TP) and are dispensed study medication. Treatment refers to the treatment assigned during TP randomization rather than the actual treatment received. ITT population is the primary analysis population for the primary and secondary endpoints.
Arm/Group Title NB32 Placebo
Hide Arm/Group Description:

NB32: Naltrexone SR 32 mg/Bupropion SR 360 mg/day. Administered in addition to the weight management program.

Weight Management Program: A comprehensive weight management program will be administered in addition to the subject's study medication assignment. The program includes internet counseling by an accredited health and fitness professional and a nutrition and exercise program with goal setting and educational and tracking tools.

Administered in addition to the weight management program.

Weight Management Program: A comprehensive weight management program will be administered in addition to the subject's study medication assignment. The program includes internet counseling by an accredited health and fitness professional and a nutrition and exercise program with goal setting and educational and tracking tools.

Overall Number of Participants Analyzed 4455 4450
Measure Type: Count of Participants
Unit of Measure: Participants
22
   0.5%
21
   0.5%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection NB32, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Cox Proportional Hazard
Estimated Value 1.04
Confidence Interval (2-Sided) 99.7%
0.43 to 2.55
Estimation Comments Hazard ratio is based on CPH model with treatment as a factor.
Time Frame Treatment-emergent serious adverse events and treatment-emergent adverse events leading to study medication discontinuation are defined as those events with onset coincident with treatment period randomization starting at Visit 3 (Day 1) and through end of study or 30 days after discontinuation of study medication (whichever one is earlier).
Adverse Event Reporting Description Safety data is based on all available data at the time of database lock, which occurred after the pre-planned 50% interim analysis.
 
Arm/Group Title NB32 Placebo
Hide Arm/Group Description

NB32: Naltrexone SR 32 mg/Bupropion SR 360 mg/day. Administered in addition to the weight management program.

Weight Management Program: A comprehensive weight management program will be administered in addition to the subject's study medication assignment. The program includes internet counseling by an accredited health and fitness professional and a nutrition and exercise program with goal setting and educational and tracking tools.

Administered in addition to the weight management program.

Weight Management Program: A comprehensive weight management program will be administered in addition to the subject's study medication assignment. The program includes internet counseling by an accredited health and fitness professional and a nutrition and exercise program with goal setting and educational and tracking tools.

All-Cause Mortality
NB32 Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
NB32 Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   463/4455 (10.39%)      386/4450 (8.67%)    
Blood and lymphatic system disorders     
Anaemia  2/4455 (0.04%)  3 2/4450 (0.04%)  2
Haemorrhagic anaemia  0/4455 (0.00%)  0 1/4450 (0.02%)  1
Iron deficiency anaemia  1/4455 (0.02%)  1 1/4450 (0.02%)  1
Lymphadenopathy  1/4455 (0.02%)  1 1/4450 (0.02%)  1
Cardiac disorders     
Accelerated idioventricular rhythm  0/4455 (0.00%)  0 1/4450 (0.02%)  1
Acute coronary syndrome  4/4455 (0.09%)  6 3/4450 (0.07%)  3
Acute myocardial infarction  11/4455 (0.25%)  11 7/4450 (0.16%)  7
Angina pectoris  17/4455 (0.38%)  17 15/4450 (0.34%)  15
Angina unstable  22/4455 (0.49%)  25 15/4450 (0.34%)  16
Aortic valve disease  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Arrhythmia  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Arteriosclerosis coronary artery  2/4455 (0.04%)  2 1/4450 (0.02%)  1
Atrial fibrillation  12/4455 (0.27%)  12 15/4450 (0.34%)  15
Atrial flutter  4/4455 (0.09%)  5 2/4450 (0.04%)  2
Atrial tachycardia  2/4455 (0.04%)  2 0/4450 (0.00%)  0
Atrial thrombosis  0/4455 (0.00%)  0 1/4450 (0.02%)  1
Atrioventricular block  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Atrioventricular block complete  1/4455 (0.02%)  1 2/4450 (0.04%)  2
Cardiac arrest  2/4455 (0.04%)  2 1/4450 (0.02%)  1
Cardiac failure  2/4455 (0.04%)  3 1/4450 (0.02%)  1
Cardiac failure acute  0/4455 (0.00%)  0 2/4450 (0.04%)  2
Cardiac failure congestive  13/4455 (0.29%)  16 8/4450 (0.18%)  11
Cardio-respiratory arrest  1/4455 (0.02%)  1 2/4450 (0.04%)  2
Chronotropic incompetence  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Congestive cardiomyopathy  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Coronary artery disease  21/4455 (0.47%)  22 21/4450 (0.47%)  21
Coronary artery occlusion  0/4455 (0.00%)  0 5/4450 (0.11%)  5
Coronary artery stenosis  1/4455 (0.02%)  1 1/4450 (0.02%)  1
Ischaemic cardiomyopathy  1/4455 (0.02%)  1 2/4450 (0.04%)  2
Myocardial infarction  14/4455 (0.31%)  14 13/4450 (0.29%)  13
Myocardial ischaemia  2/4455 (0.04%)  2 2/4450 (0.04%)  2
Palpitations  0/4455 (0.00%)  0 1/4450 (0.02%)  1
Pericardial effusion  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Sick sinus syndrome  2/4455 (0.04%)  2 1/4450 (0.02%)  1
Supraventricular tachycardia  1/4455 (0.02%)  1 1/4450 (0.02%)  1
Tachycardia  2/4455 (0.04%)  2 1/4450 (0.02%)  1
Ventricular fibrillation  0/4455 (0.00%)  0 1/4450 (0.02%)  1
Ventricular tachycardia  3/4455 (0.07%)  3 2/4450 (0.04%)  2
Congenital, familial and genetic disorders     
Haemorrhagic arteriovenous malformation  0/4455 (0.00%)  0 1/4450 (0.02%)  1
Porphyria acute  0/4455 (0.00%)  0 1/4450 (0.02%)  1
Ear and labyrinth disorders     
Vertigo  1/4455 (0.02%)  1 2/4450 (0.04%)  2
Endocrine disorders     
Adrenal insufficiency  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Goitre  0/4455 (0.00%)  0 1/4450 (0.02%)  1
Hyperparathyroidism  0/4455 (0.00%)  0 2/4450 (0.04%)  2
Gastrointestinal disorders     
Abdominal adhesions  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Abdominal hernia  1/4455 (0.02%)  1 2/4450 (0.04%)  2
Abdominal hernia obstructive  0/4455 (0.00%)  0 1/4450 (0.02%)  1
Abdominal pain  2/4455 (0.04%)  2 3/4450 (0.07%)  3
Abdominal pain lower  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Abdominal pain upper  0/4455 (0.00%)  0 1/4450 (0.02%)  1
Abdominal strangulated hernia  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Colitis  3/4455 (0.07%)  3 0/4450 (0.00%)  0
Colitis ischaemic  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Constipation  2/4455 (0.04%)  2 0/4450 (0.00%)  0
Crohn's disease  0/4455 (0.00%)  0 1/4450 (0.02%)  1
Diverticulum intestinal haemorrhagic  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Duodenal ulcer haemorrhage  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Duodenitis  0/4455 (0.00%)  0 1/4450 (0.02%)  1
Enteritis  2/4455 (0.04%)  2 0/4450 (0.00%)  0
Gastric ulcer haemorrhage  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Gastritis  0/4455 (0.00%)  0 2/4450 (0.04%)  2
Gastrointestinal haemorrhage  1/4455 (0.02%)  1 1/4450 (0.02%)  1
Gastrointestinal ulcer  1/4455 (0.02%)  1 1/4450 (0.02%)  1
Gastrointestinal ulcer haemorrhage  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Gastrooesophageal reflux disease  2/4455 (0.04%)  2 1/4450 (0.02%)  1
Haematochezia  2/4455 (0.04%)  2 0/4450 (0.00%)  0
Hiatus hernia  2/4455 (0.04%)  2 1/4450 (0.02%)  1
Hiatus hernia, obstructive  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Impaired gastric emptying  1/4455 (0.02%)  2 0/4450 (0.00%)  0
Inguinal hernia  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Intestinal perforation  0/4455 (0.00%)  0 1/4450 (0.02%)  1
Large intestine polyp  0/4455 (0.00%)  0 1/4450 (0.02%)  1
Lower gastrointestinal haemorrhage  2/4455 (0.04%)  2 0/4450 (0.00%)  0
Nausea  1/4455 (0.02%)  2 0/4450 (0.00%)  0
Obstruction gastric  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Oesophageal spasm  0/4455 (0.00%)  0 1/4450 (0.02%)  1
Oesophagitis  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Oesophagitis haemorrhagic  0/4455 (0.00%)  0 1/4450 (0.02%)  1
Pancreatitis  3/4455 (0.07%)  3 4/4450 (0.09%)  4
Pancreatitis acute  3/4455 (0.07%)  3 1/4450 (0.02%)  1
Peptic ulcer  0/4455 (0.00%)  0 1/4450 (0.02%)  1
Retroperitoneal haemorrhage  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Small intestinal obstruction  9/4455 (0.20%)  10 3/4450 (0.07%)  5
Umbilical hernia  1/4455 (0.02%)  1 1/4450 (0.02%)  1
Umbilical hernia, obstructive  0/4455 (0.00%)  0 2/4450 (0.04%)  2
Upper gastrointestinal haemorrhage  0/4455 (0.00%)  0 1/4450 (0.02%)  1
Vomiting  2/4455 (0.04%)  3 0/4450 (0.00%)  0
General disorders     
Asthenia  0/4455 (0.00%)  0 1/4450 (0.02%)  1
Chest discomfort  0/4455 (0.00%)  0 2/4450 (0.04%)  2
Chest pain  15/4455 (0.34%)  15 9/4450 (0.20%)  9
Cyst  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Death  4/4455 (0.09%)  4 2/4450 (0.04%)  2
Device dislocation  1/4455 (0.02%)  1 1/4450 (0.02%)  1
Device malfunction  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Fat tissue increased  0/4455 (0.00%)  0 1/4450 (0.02%)  1
Ischaemic ulcer  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Non-cardiac chest pain  22/4455 (0.49%)  22 13/4450 (0.29%)  13
Pyrexia  0/4455 (0.00%)  0 2/4450 (0.04%)  2
Sudden cardiac death  0/4455 (0.00%)  0 1/4450 (0.02%)  1
Surgical failure  0/4455 (0.00%)  0 1/4450 (0.02%)  1
Systemic inflammatory response syndrome  1/4455 (0.02%)  1 1/4450 (0.02%)  1
Unevaluable event  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Hepatobiliary disorders     
Bile duct stone  1/4455 (0.02%)  1 1/4450 (0.02%)  1
Biliary colic  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Biliary dyskinesia  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Cholecystitis  2/4455 (0.04%)  2 4/4450 (0.09%)  4
Cholecystitis acute  4/4455 (0.09%)  4 5/4450 (0.11%)  5
Cholecystitis chronic  1/4455 (0.02%)  1 1/4450 (0.02%)  1
Cholelithiasis  2/4455 (0.04%)  2 2/4450 (0.04%)  2
Drug-induced liver injury  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Gallbladder disorder  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Gallbladder polyp  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Hepatic cyst  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Immune system disorders     
Anaphylactic reaction  0/4455 (0.00%)  0 1/4450 (0.02%)  1
Hypersensitivity  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Infections and infestations     
Abdominal wall abscess  0/4455 (0.00%)  0 1/4450 (0.02%)  1
Abscess  0/4455 (0.00%)  0 2/4450 (0.04%)  2
Abscess limb  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Appendicitis  1/4455 (0.02%)  1 3/4450 (0.07%)  3
Appendicitis perforated  0/4455 (0.00%)  0 1/4450 (0.02%)  1
Arthritis bacterial  0/4455 (0.00%)  0 1/4450 (0.02%)  1
Bronchitis  1/4455 (0.02%)  1 2/4450 (0.04%)  2
Bursitis infective staphylococcal  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Cellulitis  16/4455 (0.36%)  17 8/4450 (0.18%)  8
Cellulitis of male external genital organ  0/4455 (0.00%)  0 1/4450 (0.02%)  1
Cellulitis staphylococcal  0/4455 (0.00%)  0 1/4450 (0.02%)  1
Clostridium difficile colitis  1/4455 (0.02%)  1 1/4450 (0.02%)  1
Clostridium difficile infection  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Colonic abscess  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Diverticulitis  3/4455 (0.07%)  3 6/4450 (0.13%)  7
Escherichia bacteraemia  0/4455 (0.00%)  0 1/4450 (0.02%)  1
Gastroenteritis  3/4455 (0.07%)  5 2/4450 (0.04%)  2
Gastroenteritis bacterial  0/4455 (0.00%)  0 1/4450 (0.02%)  1
Gastroenteritis viral  0/4455 (0.00%)  0 1/4450 (0.02%)  1
Human ehrlichiosis  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Infected bites  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Infection  0/4455 (0.00%)  0 1/4450 (0.02%)  1
Influenza  1/4455 (0.02%)  1 1/4450 (0.02%)  1
Intervertebral discitis  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Lobar pneumonia  1/4455 (0.02%)  1 1/4450 (0.02%)  1
Lung infection  0/4455 (0.00%)  0 1/4450 (0.02%)  1
Osteomyelitis  3/4455 (0.07%)  3 1/4450 (0.02%)  1
Perirectal abscess  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Pharyngeal abscess  0/4455 (0.00%)  0 1/4450 (0.02%)  1
Pneumonia  12/4455 (0.27%)  13 10/4450 (0.22%)  10
Pneumonia staphylococcal  0/4455 (0.00%)  0 1/4450 (0.02%)  1
Pyelonephritis  0/4455 (0.00%)  0 1/4450 (0.02%)  1
Sepsis  2/4455 (0.04%)  2 5/4450 (0.11%)  5
Septic shock  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Staphylococcal infection  1/4455 (0.02%)  1 1/4450 (0.02%)  1
Upper respiratory tract infection  0/4455 (0.00%)  0 1/4450 (0.02%)  1
Urinary tract infection  2/4455 (0.04%)  2 3/4450 (0.07%)  3
Urinary tract infection bacterial  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Urosepsis  0/4455 (0.00%)  0 1/4450 (0.02%)  1
Wound abscess  0/4455 (0.00%)  0 1/4450 (0.02%)  1
Injury, poisoning and procedural complications     
Acetabulum fracture  0/4455 (0.00%)  0 1/4450 (0.02%)  1
Ankle fracture  5/4455 (0.11%)  5 4/4450 (0.09%)  4
Cervical vertebral fracture  2/4455 (0.04%)  2 0/4450 (0.00%)  0
Concussion  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Craniocerebral injury  2/4455 (0.04%)  2 0/4450 (0.00%)  0
Cystitis radiation  0/4455 (0.00%)  0 1/4450 (0.02%)  1
Fall  2/4455 (0.04%)  2 0/4450 (0.00%)  0
Femoral neck fracture  0/4455 (0.00%)  0 1/4450 (0.02%)  1
Femur fracture  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Gastrointestinal stoma complication  0/4455 (0.00%)  0 1/4450 (0.02%)  1
Gun shot wound  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Head injury  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Hip fracture  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Humerus fracture  1/4455 (0.02%)  1 2/4450 (0.04%)  2
Incisional hernia  2/4455 (0.04%)  2 1/4450 (0.02%)  1
Joint dislocation  1/4455 (0.02%)  1 2/4450 (0.04%)  2
Joint injury  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Lower limb fracture  0/4455 (0.00%)  0 1/4450 (0.02%)  1
Meniscus injury  0/4455 (0.00%)  0 1/4450 (0.02%)  1
Multiple injuries  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Postoperative ileus  0/4455 (0.00%)  0 1/4450 (0.02%)  1
Postoperative respiratory failure  0/4455 (0.00%)  0 1/4450 (0.02%)  1
Procedural pain  1/4455 (0.02%)  2 0/4450 (0.00%)  0
Radius fracture  2/4455 (0.04%)  2 0/4450 (0.00%)  0
Rib fracture  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Road traffic accident  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Skull fracture  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Spinal column injury  0/4455 (0.00%)  0 1/4450 (0.02%)  1
Spinal cord injury  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Spinal fracture  2/4455 (0.04%)  2 2/4450 (0.04%)  2
Subdural haematoma  2/4455 (0.04%)  2 0/4450 (0.00%)  0
Tendon rupture  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Thermal burn  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Ulna fracture  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Upper limb fracture  0/4455 (0.00%)  0 2/4450 (0.04%)  2
Wound dehiscence  0/4455 (0.00%)  0 1/4450 (0.02%)  1
Wrist fracture  0/4455 (0.00%)  0 1/4450 (0.02%)  1
Investigations     
Anticoagulation drug level below therapeutic  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Blood potassium decreased  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Blood potassium increased  0/4455 (0.00%)  0 1/4450 (0.02%)  1
Blood pressure increased  2/4455 (0.04%)  2 0/4450 (0.00%)  0
Thyroid function test abnormal  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Troponin increased  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Metabolism and nutrition disorders     
Alkalosis hypochloraemic  0/4455 (0.00%)  0 1/4450 (0.02%)  1
Dehydration  6/4455 (0.13%)  6 1/4450 (0.02%)  1
Diabetes mellitus inadequate control  1/4455 (0.02%)  1 1/4450 (0.02%)  1
Fluid overload  0/4455 (0.00%)  0 1/4450 (0.02%)  1
Hyperglycaemia  1/4455 (0.02%)  1 1/4450 (0.02%)  1
Hypoglycaemia  5/4455 (0.11%)  5 1/4450 (0.02%)  1
Hypokalaemia  1/4455 (0.02%)  1 1/4450 (0.02%)  1
Hyponatraemia  1/4455 (0.02%)  1 3/4450 (0.07%)  3
Metabolic acidosis  0/4455 (0.00%)  0 1/4450 (0.02%)  1
Obesity  1/4455 (0.02%)  1 4/4450 (0.09%)  4
Musculoskeletal and connective tissue disorders     
Arthralgia  3/4455 (0.07%)  3 1/4450 (0.02%)  1
Arthritis  4/4455 (0.09%)  4 1/4450 (0.02%)  1
Back pain  0/4455 (0.00%)  0 1/4450 (0.02%)  1
Bursitis  1/4455 (0.02%)  1 1/4450 (0.02%)  1
Cervical spinal stenosis  1/4455 (0.02%)  2 1/4450 (0.02%)  1
Exostosis  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Intervertebral disc compression  0/4455 (0.00%)  0 1/4450 (0.02%)  1
Intervertebral disc degeneration  3/4455 (0.07%)  3 2/4450 (0.04%)  2
Intervertebral disc disorder  0/4455 (0.00%)  0 1/4450 (0.02%)  1
Intervertebral disc protrusion  5/4455 (0.11%)  5 1/4450 (0.02%)  1
Lumbar spinal stenosis  8/4455 (0.18%)  9 1/4450 (0.02%)  1
Musculoskeletal chest pain  1/4455 (0.02%)  1 1/4450 (0.02%)  1
Musculoskeletal pain  0/4455 (0.00%)  0 1/4450 (0.02%)  1
Neck pain  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Osteoarthritis  40/4455 (0.90%)  42 41/4450 (0.92%)  44
Osteoarthropathy  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Osteonecrosis  0/4455 (0.00%)  0 1/4450 (0.02%)  1
Pain in extremity  1/4455 (0.02%)  2 0/4450 (0.00%)  0
Resorption bone increased  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Rheumatoid arthritis  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Rotator cuff syndrome  1/4455 (0.02%)  1 1/4450 (0.02%)  1
Spinal column stenosis  2/4455 (0.04%)  2 4/4450 (0.09%)  4
Spinal ligament ossification  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Spinal osteoarthritis  3/4455 (0.07%)  3 1/4450 (0.02%)  1
Spondylolisthesis  4/4455 (0.09%)  4 1/4450 (0.02%)  1
Synovial cyst  2/4455 (0.04%)  2 1/4450 (0.02%)  1
Vertebral osteophyte  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Acute myeloid leukaemia  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Adenocarcinoma gastric  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Adenocarcinoma pancreas  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Adenoma benign  1/4455 (0.02%)  1 0/4450 (0.00%)  0
B-cell lymphoma  0/4455 (0.00%)  0 1/4450 (0.02%)  1
B-cell unclassifiable lymphoma high grade  0/4455 (0.00%)  0 1/4450 (0.02%)  1
Basal cell carcinoma  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Benign lung neoplasm  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Bladder cancer  0/4455 (0.00%)  0 1/4450 (0.02%)  1
Bladder transitional cell carcinoma  1/4455 (0.02%)  1 1/4450 (0.02%)  1
Bowen's disease  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Breast cancer  6/4455 (0.13%)  6 5/4450 (0.11%)  5
Cholangiocarcinoma  0/4455 (0.00%)  0 1/4450 (0.02%)  1
Clear cell renal cell carcinoma  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Colon adenoma  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Colon cancer  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Colon cancer metastatic  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Endometrial adenocarcinoma  2/4455 (0.04%)  2 0/4450 (0.00%)  0
Endometrial cancer  2/4455 (0.04%)  2 1/4450 (0.02%)  1
Glioblastoma  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Glioblastoma multiforme  0/4455 (0.00%)  0 1/4450 (0.02%)  1
Invasive ductal breast carcinoma  1/4455 (0.02%)  1 1/4450 (0.02%)  1
Leukaemia  0/4455 (0.00%)  0 1/4450 (0.02%)  1
Lung adenocarcinoma  0/4455 (0.00%)  0 1/4450 (0.02%)  1
Lung neoplasm malignant  0/4455 (0.00%)  0 1/4450 (0.02%)  1
Malignant melanoma  1/4455 (0.02%)  1 1/4450 (0.02%)  1
Malignant melanoma in situ  0/4455 (0.00%)  0 1/4450 (0.02%)  1
Mesothelioma  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Metastases to liver  0/4455 (0.00%)  0 1/4450 (0.02%)  1
Metastases to spleen  0/4455 (0.00%)  0 1/4450 (0.02%)  1
Metastatic neoplasm  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Metastatic squamous cell carcinoma  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Non-Hodgkin's lymphoma  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Oesophageal adenocarcinoma  0/4455 (0.00%)  0 2/4450 (0.04%)  2
Oesophageal cancer metastatic  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Ovarian cancer  0/4455 (0.00%)  0 1/4450 (0.02%)  1
Ovarian granulosa cell tumour  0/4455 (0.00%)  0 1/4450 (0.02%)  1
Pancreatic carcinoma  1/4455 (0.02%)  1 3/4450 (0.07%)  3
Phaeochromocytoma  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Prostate cancer  3/4455 (0.07%)  3 6/4450 (0.13%)  6
Prostate cancer stage II  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Renal cancer  2/4455 (0.04%)  2 2/4450 (0.04%)  2
Renal cell carcinoma  1/4455 (0.02%)  1 3/4450 (0.07%)  3
Squamous cell carcinoma of skin  0/4455 (0.00%)  0 1/4450 (0.02%)  1
Thymoma  0/4455 (0.00%)  0 1/4450 (0.02%)  1
Thyroid neoplasm  2/4455 (0.04%)  2 1/4450 (0.02%)  1
Tongue neoplasm malignant stage unspecified  0/4455 (0.00%)  0 1/4450 (0.02%)  1
Tonsil cancer  0/4455 (0.00%)  0 1/4450 (0.02%)  1
Uterine cancer  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Uterine leiomyoma  0/4455 (0.00%)  0 3/4450 (0.07%)  3
Nervous system disorders     
Aphasia  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Brain stem stroke  0/4455 (0.00%)  0 1/4450 (0.02%)  1
Carotid artery disease  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Carotid artery occlusion  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Carotid artery stenosis  2/4455 (0.04%)  2 2/4450 (0.04%)  2
Cerebellar haemorrhage  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Cerebral infarction  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Cerebrovascular accident  7/4455 (0.16%)  7 5/4450 (0.11%)  5
Complicated migraine  0/4455 (0.00%)  0 1/4450 (0.02%)  1
Convulsion  2/4455 (0.04%)  2 0/4450 (0.00%)  0
Dementia with Lewy bodies  0/4455 (0.00%)  0 1/4450 (0.02%)  1
Diabetic hyperosmolar coma  0/4455 (0.00%)  0 1/4450 (0.02%)  1
Dizziness  4/4455 (0.09%)  4 1/4450 (0.02%)  1
Encephalopathy  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Haemorrhage intracranial  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Headache  0/4455 (0.00%)  0 1/4450 (0.02%)  1
Hemiparesis  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Hydrocephalus  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Hypoaesthesia  0/4455 (0.00%)  0 1/4450 (0.02%)  1
Ischaemic stroke  2/4455 (0.04%)  2 0/4450 (0.00%)  0
Lacunar infarction  2/4455 (0.04%)  2 1/4450 (0.02%)  1
Lumbar radiculopathy  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Metabolic encephalopathy  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Nerve root compression  0/4455 (0.00%)  0 1/4450 (0.02%)  1
Normal pressure hydrocephalus  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Paraesthesia  0/4455 (0.00%)  0 1/4450 (0.02%)  1
Presyncope  0/4455 (0.00%)  0 1/4450 (0.02%)  1
Spondylitic myelopathy  2/4455 (0.04%)  2 0/4450 (0.00%)  0
Subarachnoid haemorrhage  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Syncope  7/4455 (0.16%)  7 6/4450 (0.13%)  6
Transient ischaemic attack  2/4455 (0.04%)  3 4/4450 (0.09%)  4
VIIth nerve paralysis  0/4455 (0.00%)  0 2/4450 (0.04%)  2
Psychiatric disorders     
Alcohol withdrawal syndrome  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Bipolar disorder  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Delirium  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Depression  0/4455 (0.00%)  0 1/4450 (0.02%)  1
Hallucination  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Major depression  3/4455 (0.07%)  3 0/4450 (0.00%)  0
Mental status changes  2/4455 (0.04%)  2 0/4450 (0.00%)  0
Suicidal ideation  0/4455 (0.00%)  0 1/4450 (0.02%)  1
Renal and urinary disorders     
Acute prerenal failure  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Haematuria  0/4455 (0.00%)  0 1/4450 (0.02%)  1
Nephrolithiasis  2/4455 (0.04%)  2 4/4450 (0.09%)  4
Nephrosclerosis  0/4455 (0.00%)  0 1/4450 (0.02%)  1
Obstructive uropathy  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Renal failure  1/4455 (0.02%)  1 2/4450 (0.04%)  2
Renal failure acute  8/4455 (0.18%)  8 11/4450 (0.25%)  11
Renal failure chronic  0/4455 (0.00%)  0 2/4450 (0.04%)  2
Urinary retention  0/4455 (0.00%)  0 1/4450 (0.02%)  1
Reproductive system and breast disorders     
Benign prostatic hyperplasia  2/4455 (0.04%)  2 1/4450 (0.02%)  1
Cystocele  1/4455 (0.02%)  1 2/4450 (0.04%)  2
Endometrial hyperplasia  2/4455 (0.04%)  2 0/4450 (0.00%)  0
Ovarian mass  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Pelvic prolapse  0/4455 (0.00%)  0 1/4450 (0.02%)  1
Rectocele  1/4455 (0.02%)  1 1/4450 (0.02%)  1
Uterine prolapse  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Uterovaginal prolapse  0/4455 (0.00%)  0 1/4450 (0.02%)  1
Respiratory, thoracic and mediastinal disorders     
Acute pulmonary oedema  0/4455 (0.00%)  0 1/4450 (0.02%)  1
Acute respiratory failure  4/4455 (0.09%)  4 2/4450 (0.04%)  2
Asthma  1/4455 (0.02%)  1 3/4450 (0.07%)  3
Bronchospasm  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Chronic obstructive pulmonary disease  6/4455 (0.13%)  10 4/4450 (0.09%)  5
Dyspnoea  1/4455 (0.02%)  1 1/4450 (0.02%)  1
Dyspnoea exertional  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Hypoxia  0/4455 (0.00%)  0 1/4450 (0.02%)  1
Pleural effusion  1/4455 (0.02%)  1 1/4450 (0.02%)  1
Pleurisy  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Pleuritic pain  2/4455 (0.04%)  2 0/4450 (0.00%)  0
Pneumothorax  1/4455 (0.02%)  1 1/4450 (0.02%)  1
Pulmonary embolism  2/4455 (0.04%)  2 6/4450 (0.13%)  7
Pulmonary haemorrhage  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Pulmonary hypertension  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Pulmonary thrombosis  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Respiratory distress  0/4455 (0.00%)  0 1/4450 (0.02%)  1
Respiratory failure  4/4455 (0.09%)  5 1/4450 (0.02%)  1
Skin and subcutaneous tissue disorders     
Angioedema  0/4455 (0.00%)  0 1/4450 (0.02%)  1
Skin ulcer  0/4455 (0.00%)  0 1/4450 (0.02%)  1
Subcutaneous emphysema  0/4455 (0.00%)  0 1/4450 (0.02%)  1
Surgical and medical procedures     
Gastrectomy  0/4455 (0.00%)  0 1/4450 (0.02%)  1
Hip surgery  0/4455 (0.00%)  0 1/4450 (0.02%)  1
Vascular disorders     
Accelerated hypertension  0/4455 (0.00%)  0 1/4450 (0.02%)  1
Aortic aneurysm  1/4455 (0.02%)  1 1/4450 (0.02%)  1
Aortic stenosis  0/4455 (0.00%)  0 2/4450 (0.04%)  2
Arterial occlusive disease  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Deep vein thrombosis  3/4455 (0.07%)  3 1/4450 (0.02%)  1
Haematoma  2/4455 (0.04%)  2 0/4450 (0.00%)  0
Hypertensive crisis  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Hypotension  2/4455 (0.04%)  2 4/4450 (0.09%)  4
Iliac artery occlusion  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Orthostatic hypotension  3/4455 (0.07%)  3 0/4450 (0.00%)  0
Peripheral artery thrombosis  0/4455 (0.00%)  0 1/4450 (0.02%)  1
Peripheral ischaemia  0/4455 (0.00%)  0 1/4450 (0.02%)  1
Peripheral vascular disorder  1/4455 (0.02%)  1 1/4450 (0.02%)  1
Subclavian artery stenosis  0/4455 (0.00%)  0 1/4450 (0.02%)  1
1
Term from vocabulary, MedDRA 15.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
NB32 Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   1157/4455 (25.97%)      282/4450 (6.34%)    
Cardiac disorders     
Angina pectoris  4/4455 (0.09%)  4 1/4450 (0.02%)  1
Atrial fibrillation  0/4455 (0.00%)  0 1/4450 (0.02%)  1
Bradycardia  3/4455 (0.07%)  3 0/4450 (0.00%)  0
Cardiac discomfort  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Cardiac failure congestive  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Cardiac flutter  2/4455 (0.04%)  2 0/4450 (0.00%)  0
Extrasystoles  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Palpitations  20/4455 (0.45%)  20 5/4450 (0.11%)  5
Tachycardia  3/4455 (0.07%)  3 2/4450 (0.04%)  2
Ear and labyrinth disorders     
Hearing impaired  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Tinnitus  5/4455 (0.11%)  5 1/4450 (0.02%)  1
Vertigo  11/4455 (0.25%)  11 1/4450 (0.02%)  1
Vertigo positional  0/4455 (0.00%)  0 1/4450 (0.02%)  1
Eye disorders     
Blepharospasm  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Diplopia  2/4455 (0.04%)  2 0/4450 (0.00%)  0
Vision blurred  2/4455 (0.04%)  2 0/4450 (0.00%)  0
Visual acuity reduced  0/4455 (0.00%)  0 1/4450 (0.02%)  1
Gastrointestinal disorders     
Abdominal discomfort  27/4455 (0.61%)  27 3/4450 (0.07%)  3
Abdominal distension  4/4455 (0.09%)  4 1/4450 (0.02%)  1
Abdominal pain  18/4455 (0.40%)  18 6/4450 (0.13%)  6
Abdominal pain lower  2/4455 (0.04%)  2 0/4450 (0.00%)  0
Abdominal pain upper  18/4455 (0.40%)  18 4/4450 (0.09%)  4
Bowel movement irregularity  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Coeliac disease  0/4455 (0.00%)  0 2/4450 (0.04%)  2
Colitis  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Constipation  129/4455 (2.90%)  129 15/4450 (0.34%)  15
Diarrhoea  35/4455 (0.79%)  35 21/4450 (0.47%)  21
Diverticulum  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Dry mouth  21/4455 (0.47%)  21 2/4450 (0.04%)  2
Dyspepsia  12/4455 (0.27%)  12 1/4450 (0.02%)  1
Dysphagia  3/4455 (0.07%)  3 0/4450 (0.00%)  0
Epigastric discomfort  0/4455 (0.00%)  0 1/4450 (0.02%)  1
Eructation  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Faecal incontinence  0/4455 (0.00%)  0 1/4450 (0.02%)  1
Flatulence  3/4455 (0.07%)  3 1/4450 (0.02%)  1
Frequent bowel movements  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Gastritis  2/4455 (0.04%)  2 0/4450 (0.00%)  0
Gastrointestinal hypermotility  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Gastrooesophageal reflux disease  6/4455 (0.13%)  6 3/4450 (0.07%)  3
Haematemesis  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Haematochezia  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Haemorrhoids  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Hypoaesthesia oral  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Intestinal obstruction  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Irritable bowel syndrome  2/4455 (0.04%)  2 2/4450 (0.04%)  2
Lip swelling  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Nausea  346/4455 (7.77%)  346 21/4450 (0.47%)  21
Oesophageal rupture  0/4455 (0.00%)  0 1/4450 (0.02%)  1
Pancreatitis  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Retching  3/4455 (0.07%)  3 1/4450 (0.02%)  1
Stomatitis  2/4455 (0.04%)  2 0/4450 (0.00%)  0
Upper gastrointestinal haemorrhage  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Vomiting  89/4455 (2.00%)  89 1/4450 (0.02%)  1
Vomiting projectile  1/4455 (0.02%)  1 0/4450 (0.00%)  0
General disorders     
Asthenia  2/4455 (0.04%)  2 2/4450 (0.04%)  2
Chest discomfort  2/4455 (0.04%)  2 1/4450 (0.02%)  1
Chest pain  0/4455 (0.00%)  0 1/4450 (0.02%)  1
Drug intolerance  3/4455 (0.07%)  3 2/4450 (0.04%)  2
Fatigue  13/4455 (0.29%)  13 1/4450 (0.02%)  1
Feeling abnormal  7/4455 (0.16%)  7 0/4450 (0.00%)  0
Feeling cold  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Feeling jittery  16/4455 (0.36%)  16 1/4450 (0.02%)  1
Feeling of body temperature change  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Gait disturbance  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Generalised oedema  0/4455 (0.00%)  0 1/4450 (0.02%)  1
Influenza like illness  3/4455 (0.07%)  3 0/4450 (0.00%)  0
Local swelling  0/4455 (0.00%)  0 1/4450 (0.02%)  1
Mucosal dryness  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Non-cardiac chest pain  3/4455 (0.07%)  3 1/4450 (0.02%)  1
Oedema peripheral  0/4455 (0.00%)  0 1/4450 (0.02%)  1
Pain  2/4455 (0.04%)  2 0/4450 (0.00%)  0
Hepatobiliary disorders     
Cholelithiasis  0/4455 (0.00%)  0 2/4450 (0.04%)  2
Hepatic cirrhosis  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Immune system disorders     
Drug hypersensitivity  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Hypersensitivity  0/4455 (0.00%)  0 1/4450 (0.02%)  1
Infections and infestations     
Acute sinusitis  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Bronchitis  1/4455 (0.02%)  1 1/4450 (0.02%)  1
Bronchopneumonia  0/4455 (0.00%)  0 1/4450 (0.02%)  1
Diverticulitis  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Gastroenteritis  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Helicobacter infection  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Impetigo  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Influenza  1/4455 (0.02%)  1 2/4450 (0.04%)  2
Pharyngitis streptococcal  0/4455 (0.00%)  0 1/4450 (0.02%)  1
Pneumonia  2/4455 (0.04%)  2 1/4450 (0.02%)  1
Sinusitis  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Upper respiratory tract infection  1/4455 (0.02%)  1 1/4450 (0.02%)  1
Urinary tract infection  1/4455 (0.02%)  1 1/4450 (0.02%)  1
Viral infection  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Injury, poisoning and procedural complications     
Ankle fracture  0/4455 (0.00%)  0 1/4450 (0.02%)  1
Foot fracture  0/4455 (0.00%)  0 1/4450 (0.02%)  1
Humerus fracture  1/4455 (0.02%)  1 1/4450 (0.02%)  1
Joint injury  0/4455 (0.00%)  0 1/4450 (0.02%)  1
Ligament rupture  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Lower limb fracture  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Meniscus injury  1/4455 (0.02%)  1 1/4450 (0.02%)  1
Muscle injury  2/4455 (0.04%)  2 0/4450 (0.00%)  0
Muscle strain  0/4455 (0.00%)  0 1/4450 (0.02%)  1
Procedural pain  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Rib fracture  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Tendon injury  0/4455 (0.00%)  0 1/4450 (0.02%)  1
Tendon rupture  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Upper limb fracture  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Investigations     
Alanine aminotransferase increased  0/4455 (0.00%)  0 2/4450 (0.04%)  2
Aspartate aminotransferase increased  0/4455 (0.00%)  0 1/4450 (0.02%)  1
Blood creatinine increased  4/4455 (0.09%)  4 1/4450 (0.02%)  1
Blood glucose decreased  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Blood glucose increased  1/4455 (0.02%)  1 2/4450 (0.04%)  2
Blood pressure increased  20/4455 (0.45%)  20 14/4450 (0.31%)  14
Blood pressure systolic increased  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Grip strength decreased  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Heart rate increased  2/4455 (0.04%)  2 1/4450 (0.02%)  1
Hepatic enzyme increased  1/4455 (0.02%)  1 0/4450 (0.00%)  0
International normalised ratio increased  0/4455 (0.00%)  0 1/4450 (0.02%)  1
Prostatic specific antigen increased  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Weight increased  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Metabolism and nutrition disorders     
Decreased appetite  2/4455 (0.04%)  2 0/4450 (0.00%)  0
Diabetes mellitus  0/4455 (0.00%)  0 1/4450 (0.02%)  1
Gout  0/4455 (0.00%)  0 1/4450 (0.02%)  1
Hyperphagia  0/4455 (0.00%)  0 1/4450 (0.02%)  1
Hypoglycaemia  3/4455 (0.07%)  3 2/4450 (0.04%)  2
Increased appetite  0/4455 (0.00%)  0 1/4450 (0.02%)  1
Musculoskeletal and connective tissue disorders     
Arthralgia  6/4455 (0.13%)  6 5/4450 (0.11%)  5
Arthritis  0/4455 (0.00%)  0 1/4450 (0.02%)  1
Back pain  4/4455 (0.09%)  4 11/4450 (0.25%)  11
Intervertebral disc degeneration  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Intervertebral disc protrusion  2/4455 (0.04%)  2 1/4450 (0.02%)  1
Muscle spasms  5/4455 (0.11%)  5 1/4450 (0.02%)  1
Muscle twitching  3/4455 (0.07%)  3 0/4450 (0.00%)  0
Muscular weakness  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Musculoskeletal chest pain  0/4455 (0.00%)  0 1/4450 (0.02%)  1
Musculoskeletal pain  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Musculoskeletal stiffness  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Myalgia  2/4455 (0.04%)  2 2/4450 (0.04%)  2
Neck pain  0/4455 (0.00%)  0 1/4450 (0.02%)  1
Osteoporosis  0/4455 (0.00%)  0 1/4450 (0.02%)  1
Pain in extremity  3/4455 (0.07%)  3 4/4450 (0.09%)  4
Polymyalgia rheumatica  0/4455 (0.00%)  0 1/4450 (0.02%)  1
Rotator cuff syndrome  0/4455 (0.00%)  0 4/4450 (0.09%)  4
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Benign breast neoplasm  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Breast cancer  2/4455 (0.04%)  2 0/4450 (0.00%)  0
Malignant melanoma  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Nervous system disorders     
Altered state of consciousness  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Amnesia  3/4455 (0.07%)  3 4/4450 (0.09%)  4
Balance disorder  2/4455 (0.04%)  2 0/4450 (0.00%)  0
Burning sensation  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Carpal tunnel syndrome  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Disturbance in attention  7/4455 (0.16%)  7 2/4450 (0.04%)  2
Dizziness  64/4455 (1.44%)  67 8/4450 (0.18%)  8
Dizziness postural  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Dysgeusia  16/4455 (0.36%)  16 0/4450 (0.00%)  0
Dysgraphia  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Dyskinesia  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Essential tremor  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Headache  51/4455 (1.14%)  51 15/4450 (0.34%)  15
Hypoaesthesia  1/4455 (0.02%)  1 1/4450 (0.02%)  1
Lethargy  4/4455 (0.09%)  4 2/4450 (0.04%)  2
Memory impairment  3/4455 (0.07%)  3 4/4450 (0.09%)  4
Migraine  1/4455 (0.02%)  1 1/4450 (0.02%)  1
Multiple sclerosis  1/4455 (0.02%)  1 1/4450 (0.02%)  1
Muscle contractions involuntary  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Nerve compression  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Neurodegenerative disorder  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Paraesthesia  3/4455 (0.07%)  3 0/4450 (0.00%)  0
Parkinson's disease  0/4455 (0.00%)  0 1/4450 (0.02%)  1
Restless legs syndrome  0/4455 (0.00%)  0 1/4450 (0.02%)  1
Sciatica  0/4455 (0.00%)  0 1/4450 (0.02%)  1
Somnolence  2/4455 (0.04%)  2 2/4450 (0.04%)  2
Spinal meningeal cyst  0/4455 (0.00%)  0 1/4450 (0.02%)  1
Tremor  80/4455 (1.80%)  81 0/4450 (0.00%)  0
VIIth nerve paralysis  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Psychiatric disorders     
Abnormal behaviour  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Abnormal dreams  5/4455 (0.11%)  5 0/4450 (0.00%)  0
Affect lability  3/4455 (0.07%)  3 3/4450 (0.07%)  3
Agitation  1/4455 (0.02%)  1 1/4450 (0.02%)  1
Anger  1/4455 (0.02%)  1 1/4450 (0.02%)  1
Anxiety  26/4455 (0.58%)  26 8/4450 (0.18%)  8
Apathy  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Aversion  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Bruxism  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Confusional state  5/4455 (0.11%)  5 2/4450 (0.04%)  2
Depression  5/4455 (0.11%)  5 10/4450 (0.22%)  10
Disorientation  4/4455 (0.09%)  4 0/4450 (0.00%)  0
Fear  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Hallucination  10/4455 (0.22%)  10 0/4450 (0.00%)  0
Hallucination, auditory  2/4455 (0.04%)  2 0/4450 (0.00%)  0
Hallucination, visual  2/4455 (0.04%)  2 0/4450 (0.00%)  0
Insomnia  38/4455 (0.85%)  38 16/4450 (0.36%)  16
Irritability  7/4455 (0.16%)  7 2/4450 (0.04%)  2
Libido decreased  2/4455 (0.04%)  2 0/4450 (0.00%)  0
Major depression  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Mental disorder  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Middle insomnia  2/4455 (0.04%)  2 0/4450 (0.00%)  0
Mood altered  2/4455 (0.04%)  2 0/4450 (0.00%)  0
Mood swings  1/4455 (0.02%)  1 1/4450 (0.02%)  1
Nervousness  8/4455 (0.18%)  8 0/4450 (0.00%)  0
Nightmare  6/4455 (0.13%)  6 2/4450 (0.04%)  2
Obsessive-compulsive disorder  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Panic attack  2/4455 (0.04%)  2 0/4450 (0.00%)  0
Paranoia  0/4455 (0.00%)  0 1/4450 (0.02%)  1
Personality change  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Psychomotor retardation  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Restlessness  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Sleep disorder  2/4455 (0.04%)  2 0/4450 (0.00%)  0
Sleep talking  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Sleep terror  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Suicidal ideation  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Renal and urinary disorders     
Dysuria  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Glomerulosclerosis  0/4455 (0.00%)  0 1/4450 (0.02%)  1
Haematuria  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Nephrolithiasis  3/4455 (0.07%)  3 0/4450 (0.00%)  0
Pollakiuria  0/4455 (0.00%)  0 1/4450 (0.02%)  1
Renal colic  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Renal failure chronic  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Renal impairment  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Urinary hesitation  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Reproductive system and breast disorders     
Benign prostatic hyperplasia  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Ejaculation disorder  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Erectile dysfunction  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Vaginal prolapse  0/4455 (0.00%)  0 1/4450 (0.02%)  1
Respiratory, thoracic and mediastinal disorders     
Asthma  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Choking sensation  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Dysphonia  2/4455 (0.04%)  2 0/4450 (0.00%)  0
Dyspnoea  4/4455 (0.09%)  4 2/4450 (0.04%)  2
Dyspnoea exertional  1/4455 (0.02%)  1 1/4450 (0.02%)  1
Epistaxis  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Nasal discomfort  0/4455 (0.00%)  0 1/4450 (0.02%)  1
Oropharyngeal pain  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Paranasal sinus hypersecretion  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Pleural effusion  0/4455 (0.00%)  0 1/4450 (0.02%)  1
Pleurisy  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Pulmonary fibrosis  0/4455 (0.00%)  0 1/4450 (0.02%)  1
Sinus congestion  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Wheezing  0/4455 (0.00%)  0 1/4450 (0.02%)  1
Skin and subcutaneous tissue disorders     
Alopecia  8/4455 (0.18%)  8 3/4450 (0.07%)  3
Angioedema  0/4455 (0.00%)  0 1/4450 (0.02%)  1
Dermatitis  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Dermatitis contact  0/4455 (0.00%)  0 1/4450 (0.02%)  1
Drug eruption  2/4455 (0.04%)  2 0/4450 (0.00%)  0
Hyperhidrosis  6/4455 (0.13%)  6 1/4450 (0.02%)  1
Night sweats  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Pruritus  4/4455 (0.09%)  4 3/4450 (0.07%)  3
Pruritus generalised  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Rash  10/4455 (0.22%)  10 3/4450 (0.07%)  3
Skin irritation  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Skin reaction  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Swelling face  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Urticaria  6/4455 (0.13%)  6 3/4450 (0.07%)  3
Surgical and medical procedures     
Cardioversion  0/4455 (0.00%)  0 1/4450 (0.02%)  1
Knee arthroplasty  1/4455 (0.02%)  1 0/4450 (0.00%)  0
Vascular disorders     
Flushing  3/4455 (0.07%)  3 1/4450 (0.02%)  1
Hot flush  10/4455 (0.22%)  10 2/4450 (0.04%)  2
Hypertension  25/4455 (0.56%)  25 11/4450 (0.25%)  11
Hypotension  3/4455 (0.07%)  3 0/4450 (0.00%)  0
Labile blood pressure  0/4455 (0.00%)  0 1/4450 (0.02%)  1
1
Term from vocabulary, MedDRA 15.0
The study was terminated early. Outcome measures data is based on the 50% interim analysis, designated as the primary analysis. Safety data is based on all available data at the time of database lock, which occurred after the 50% interim analysis.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
If not already published by Sponsor as part of a multi-center publication, 24 months after conclusion, abandonment or termination of the study or notification that there will be no such multi-center publication, PI may publish the results for PI's study center individually. Prior to such publication, PI must provide Sponsor with at least 90 days to review and comment on the proposed publication. Sponsor may delay publication for up to an additional 6-month period to file for patent protection.
Results Point of Contact
Name/Title: Global Head of Development
Organization: Orexigen Therapeutics, Inc.
Phone: 858-875-8600
Responsible Party: Orexigen Therapeutics, Inc
ClinicalTrials.gov Identifier: NCT01601704     History of Changes
Other Study ID Numbers: NB-CVOT
The Light Study ( Other Identifier: Takeda )
U1111-1162-4981 ( Registry Identifier: WHO )
First Submitted: May 14, 2012
First Posted: May 18, 2012
Results First Submitted: December 11, 2016
Results First Posted: February 27, 2017
Last Update Posted: February 27, 2017