Human Papilloma Virus (HPV) Vaccine Efficacy Trial Against Cervical Pre-cancer in Young Adults With GlaxoSmithKline (GSK) Biologicals HPV-16/18

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00122681
First received: July 20, 2005
Last updated: July 11, 2013
Last verified: February 2012
Results First Received: November 30, 2009  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Investigator);   Primary Purpose: Prevention
Conditions: Human Papillomavirus (HPV) Infection
Cervical Neoplasia
Interventions: Biological: Cervarix™
Biological: Havrix™-based investigational formulation

  Participant Flow
  Hide Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Of the 18729 subjects enrolled in the study, 64 subjects were not vaccinated. Within the 18665 subjects vaccinated, 21 subjects from 1 center were excluded from all analyses because of potential data discrepancies identified at this center. As a result, a total of 18644 subjects are reported as started in the participant flow.

Reporting Groups
  Description
Havrix Group Subjects received 3 doses of GSK Biologicals' hepatitis A vaccine [HAV] (Havrix™-based investigational formulation) at Months 0, 1 and 6.
Cervarix Group Subjects received 3 doses of Cervarix™ (GSK Biologicals' human papillomavirus [HPV] vaccine) at Months 0, 1 and 6.

Participant Flow:   Overall Study
    Havrix Group     Cervarix Group  
STARTED     9325     9319  
COMPLETED     7811     7798  
NOT COMPLETED     1514     1521  
Adverse Event                 20                 16  
Lost to Follow-up                 1080                 1097  
Protocol Violation                 7                 10  
Withdrawal by Subject                 257                 251  
Personal reasons                 150                 147  



  Baseline Characteristics
  Hide Baseline Characteristics

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Havrix Group Subjects received 3 doses of GSK Biologicals' hepatitis A vaccine [HAV] (Havrix™-based investigational formulation) at Months 0, 1 and 6.
Cervarix Group Subjects received 3 doses of Cervarix™ (GSK Biologicals' human papillomavirus [HPV] vaccine) at Months 0, 1 and 6.
Total Total of all reporting groups

Baseline Measures
    Havrix Group     Cervarix Group     Total  
Number of Participants  
[units: participants]
  9325     9319     18644  
Age  
[units: years]
Mean ± Standard Deviation
  20.0  ± 3.12     20.0  ± 3.10     20.0  ± 3.11  
Gender  
[units: subjects]
     
Female     9325     9319     18644  
Male     0     0     0  



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Number of Subjects With Histopathologically-confirmed Cervical Intraepithelial Neoplasia (CIN)2+ Associated With HPV-16 and/or -18 Cervical Infection   [ Time Frame: Up to the moment when 36 cases of CIN2+ lesions associated with HPV-16 or HPV-18 infection had been detected, including at least 15 cases of CIN2+ associated with HPV-18 infection. Mean follow-up was 34.9 months post-dose 3 ]

2.  Primary:   Number of Subjects With Histopathologically-confirmed Cervical Intraepithelial Neoplasia (CIN)2+ Associated With HPV-16 and/or -18 Cervical Infection   [ Time Frame: at Month 48 ]

3.  Secondary:   Number of Subjects Reporting Solicited Local and General Symptoms   [ Time Frame: Within 7 days after any vaccination ]

4.  Secondary:   Number of Subjects Reporting Unsolicited Adverse Events   [ Time Frame: Within 30 days after any vaccination ]

5.  Secondary:   Number of Subjects Reporting Serious Adverse Events (SAEs)   [ Time Frame: Throughout the entire study period (Month 0 to Month 48) ]

6.  Secondary:   Number of Subjects Reporting New Onset of Chronic Disease (NOCDs)   [ Time Frame: Throughout the entire study (Month 0 to 48) ]

7.  Secondary:   Number of Subjects Reporting Medically Significant Conditions   [ Time Frame: Throughout entire study period (Month 0 to Month 48) ]

8.  Secondary:   Number of Subjects With Outcome of Pregnancies, Overall and Stratified by Initial (Month 0) HPV-16/18 DNA Status and According to HPV-16 or -18 Serostatus   [ Time Frame: Throughout the entire study period (Month 0 to Month 48) ]

9.  Secondary:   Number of Subjects With Persistent Infection (6-month Definition) With HPV-16 or HPV-18   [ Time Frame: Up to the moment when 36 cases of CIN2+ lesions associated with HPV-16 or HPV-18 infection had been detected, including at least 15 cases of CIN2+ associated with HPV-18 infection. Mean follow-up was 34.9 months post dose 3 ]

10.  Secondary:   Number of Subjects With Persistent Infection (6-month Definition) With HPV-16 or HPV-18   [ Time Frame: at Month 48 ]

11.  Secondary:   Number of Subjects With Persistent Infection (6-month Definition) With Oncogenic HPV Types   [ Time Frame: Up to the moment when 36 cases of CIN2+ lesions associated with HPV-16 or HPV-18 infection had been detected, including at least 15 cases of CIN2+ associated with HPV-18 infection. Mean follow-up was 34.9 months post dose 3 ]

12.  Secondary:   Number of Subjects With Persistent Infection (6-month Definition) With Oncogenic HPV Types   [ Time Frame: at Month 48 ]

13.  Secondary:   Number of Subjects With Histopathologically-confirmed Cervical Intraepithelial Neoplasia (CIN)1+ Associated With HPV-16 or HPV-18 Detected Within the Lesional Component of the Cervical Tissue Specimen   [ Time Frame: Up to the moment when 36 cases of CIN2+ lesions associated with HPV-16 or HPV-18 infection had been detected, including at least 15 cases of CIN2+ associated with HPV-18 infection. Mean follow-up was 34.9 months post dose 3 ]

14.  Secondary:   Number of Subjects With Histopathologically-confirmed Cervical Intraepithelial Neoplasia (CIN)1+ Associated With HPV-16 or HPV-18 Detected Within the Lesional Component of the Cervical Tissue Specimen   [ Time Frame: at Month 48 ]

15.  Secondary:   Number of Subjects Reporting Persistent Infection (12-month Definition) With HPV-16 or HPV-18   [ Time Frame: Up to the moment when 36 cases of CIN2+ lesions associated with HPV-16 or HPV-18 infection had been detected, including at least 15 cases of CIN2+ associated with HPV-18 infection. Mean follow-up was 34.9 months post dose 3 ]

16.  Secondary:   Number of Subjects Reporting Persistent Infection (12-month Definition) With HPV-16 or HPV-18   [ Time Frame: at Month 48 ]

17.  Secondary:   Number of Subjects With Histopathologically Confirmed Cervical Intraepithelial Neoplasia (CIN)1+ Associated With Oncogenic HPV Types Detected Within the Lesional Component of the Cervical Tissue Specimen   [ Time Frame: Up to the moment when 36 cases of CIN2+ lesions associated with HPV-16 or HPV-18 infection had been detected, including at least 15 cases of CIN2+ associated with HPV-18 infection. Mean follow-up was 34.9 months post dose 3 ]

18.  Secondary:   Number of Subjects With Histopathologically Confirmed Cervical Intraepithelial Neoplasia (CIN)1+ Associated With Oncogenic HPV Types Detected Within the Lesional Component of the Cervical Tissue Specimen   [ Time Frame: at Month 48 ]

19.  Secondary:   Number of Subjects With Histopathologically Confirmed Cervical Intraepithelial Neoplasia (CIN)2+ Associated With Oncogenic HPV Types Detected Within the Lesional Component of the Cervical Tissue Specimen   [ Time Frame: Up to the moment when 36 cases of CIN2+ lesions associated with HPV-16 or HPV-18 infection had been detected, including at least 15 cases of CIN2+ associated with HPV-18 infection. Mean follow-up was 34.9 months post dose 3 ]

20.  Secondary:   Number of Subjects With Histopathologically Confirmed Cervical Intraepithelial Neoplasia (CIN)2+ Associated With Oncogenic HPV Types Detected Within the Lesional Component of the Cervical Tissue Specimen   [ Time Frame: at Month 48 ]

21.  Secondary:   Number of Seropositive Subjects for Anti-HPV-16 and Anti-HPV-18 Antibody Titers by ELISA in the Immunogenicity Subset, According to Initial (Month 0) HPV-16 or HPV-18 Serostatus   [ Time Frame: At Months 6, 7, 12, 24, 36 & 48 ]

22.  Secondary:   Anti-HPV-16 and Anti-HPV-18 ELISA Titers in the Immunogenicity Subset   [ Time Frame: At Months 6, 7, 12, 24, 36 and 48 ]

23.  Secondary:   HPV-16 and HPV-18 Seroconversion (V5/J4 Monoclonal Inhibition Test)   [ Time Frame: Month 0, 7, 12 and 24 ]

24.  Secondary:   HPV-16 and HPV-18 Geometric Mean Titers (GMT) (V5/J4 Monoclonal Inhibition Test)   [ Time Frame: Month 0, 7, 12, 24 ]

25.  Secondary:   Number of Subjects Seropositive for Anti-HPV-16 and Anti-HPV-18 Antibodies Using Pseudovirion Based Neutralizing Assay (PBNA)   [ Time Frame: At Month 0, 7, 12, 24, 36 and 48 ]

26.  Secondary:   Titers for Anti-HPV-16 and Anti-HPV-18 Antibodies Using Pseudovirion Based Neutralizing Assay (PBNA)   [ Time Frame: At month 0, 7, 12, 24, 36 and 48 ]


  Serious Adverse Events
  Hide Serious Adverse Events

Time Frame No text entered.
Additional Description No text entered.

Reporting Groups
  Description
Havrix Group Subjects received 3 doses of GSK Biologicals' hepatitis A vaccine [HAV] (Havrix™-based investigational formulation) at Months 0, 1 and 6.
Cervarix Group Subjects received 3 doses of Cervarix™ (GSK Biologicals' human papillomavirus [HPV] vaccine) at Months 0, 1 and 6.

Serious Adverse Events
    Havrix Group     Cervarix Group  
Total, serious adverse events      
# participants affected / at risk     829/9325 (8.89%)     835/9319 (8.96%)  
Blood and lymphatic system disorders      
Anaemia * 1    
# participants affected / at risk     3/9325 (0.03%)     1/9319 (0.01%)  
Lymphadenitis * 1    
# participants affected / at risk     1/9325 (0.01%)     3/9319 (0.03%)  
Thrombocytopenia * 1    
# participants affected / at risk     1/9325 (0.01%)     1/9319 (0.01%)  
Hyperchromic anaemia * 1    
# participants affected / at risk     0/9325 (0.00%)     1/9319 (0.01%)  
Idiopathic thrombocytopenic purpura * 1    
# participants affected / at risk     0/9325 (0.00%)     1/9319 (0.01%)  
Iron deficiency anaemia * 1    
# participants affected / at risk     1/9325 (0.01%)     0/9319 (0.00%)  
Cardiac disorders      
Sinus tachycardia * 1    
# participants affected / at risk     1/9325 (0.01%)     2/9319 (0.02%)  
Supraventricular tachycardia * 1    
# participants affected / at risk     1/9325 (0.01%)     2/9319 (0.02%)  
Arrhythmia * 1    
# participants affected / at risk     0/9325 (0.00%)     2/9319 (0.02%)  
Cardio-respiratory arrest * 1    
# participants affected / at risk     2/9325 (0.02%)     0/9319 (0.00%)  
Atrial fibrillation * 1    
# participants affected / at risk     0/9325 (0.00%)     1/9319 (0.01%)  
Atrial flutter * 1    
# participants affected / at risk     0/9325 (0.00%)     1/9319 (0.01%)  
Cardiopulmonary failure * 1    
# participants affected / at risk     0/9325 (0.00%)     1/9319 (0.01%)  
Myocarditis * 1    
# participants affected / at risk     1/9325 (0.01%)     0/9319 (0.00%)  
Pericarditis * 1    
# participants affected / at risk     1/9325 (0.01%)     0/9319 (0.00%)  
Tachycardia * 1    
# participants affected / at risk     0/9325 (0.00%)     1/9319 (0.01%)  
Ventricular arrhythmia * 1    
# participants affected / at risk     0/9325 (0.00%)     1/9319 (0.01%)  
Wolff-parkinson-white syndrome * 1    
# participants affected / at risk     1/9325 (0.01%)     0/9319 (0.00%)  
Congenital, familial and genetic disorders      
Coarctation of the aorta * 1    
# participants affected / at risk     1/9325 (0.01%)     0/9319 (0.00%)  
Dermoid cyst * 1    
# participants affected / at risk     1/9325 (0.01%)     0/9319 (0.00%)  
Thyroglossal cyst * 1    
# participants affected / at risk     1/9325 (0.01%)     0/9319 (0.00%)  
Ventricular septal defect * 1    
# participants affected / at risk     1/9325 (0.01%)     0/9319 (0.00%)  
Ear and labyrinth disorders      
Deafness * 1    
# participants affected / at risk     0/9325 (0.00%)     1/9319 (0.01%)  
Deafness bilateral * 1    
# participants affected / at risk     1/9325 (0.01%)     0/9319 (0.00%)  
Meniere's disease * 1    
# participants affected / at risk     1/9325 (0.01%)     0/9319 (0.00%)  
Tympanic membrane perforation * 1    
# participants affected / at risk     1/9325 (0.01%)     0/9319 (0.00%)  
Vertigo * 1    
# participants affected / at risk     0/9325 (0.00%)     1/9319 (0.01%)  
Endocrine disorders      
Goitre * 1    
# participants affected / at risk     1/9325 (0.01%)     1/9319 (0.01%)  
Autoimmune thyroiditis * 1    
# participants affected / at risk     0/9325 (0.00%)     1/9319 (0.01%)  
Basedow’s disease * 1    
# participants affected / at risk     0/9325 (0.00%)     1/9319 (0.01%)  
Eye disorders      
Blindness unilateral * 1    
# participants affected / at risk     0/9325 (0.00%)     1/9319 (0.01%)  
Conjunctivitis * 1    
# participants affected / at risk     0/9325 (0.00%)     1/9319 (0.01%)  
Dacryostenosis acquired * 1    
# participants affected / at risk     0/9325 (0.00%)     1/9319 (0.01%)  
Retinal detachment * 1    
# participants affected / at risk     1/9325 (0.01%)     0/9319 (0.00%)  
Strabismus * 1    
# participants affected / at risk     1/9325 (0.01%)     0/9319 (0.00%)  
Vision blurred * 1    
# participants affected / at risk     0/9325 (0.00%)     1/9319 (0.01%)  
Gastrointestinal disorders      
Abdominal pain * 1    
# participants affected / at risk     15/9325 (0.16%)     16/9319 (0.17%)  
Gastritis * 1    
# participants affected / at risk     4/9325 (0.04%)     9/9319 (0.10%)  
Abdominal pain lower * 1    
# participants affected / at risk     4/9325 (0.04%)     4/9319 (0.04%)  
Abdominal pain upper * 1    
# participants affected / at risk     5/9325 (0.05%)     3/9319 (0.03%)  
Crohn's disease * 1    
# participants affected / at risk     3/9325 (0.03%)     1/9319 (0.01%)  
Pancreatitis * 1    
# participants affected / at risk     3/9325 (0.03%)     1/9319 (0.01%)  
Vomiting * 1    
# participants affected / at risk     2/9325 (0.02%)     2/9319 (0.02%)  
Colitis * 1    
# participants affected / at risk     2/9325 (0.02%)     1/9319 (0.01%)  
Diarrhoea * 1    
# participants affected / at risk     0/9325 (0.00%)     3/9319 (0.03%)  
Gastrooesophageal reflux disease * 1    
# participants affected / at risk     1/9325 (0.01%)     2/9319 (0.02%)  
Irritable bowel syndrome * 1    
# participants affected / at risk     1/9325 (0.01%)     2/9319 (0.02%)  
Tooth impacted * 1    
# participants affected / at risk     1/9325 (0.01%)     2/9319 (0.02%)  
Constipation * 1    
# participants affected / at risk     1/9325 (0.01%)     1/9319 (0.01%)  
Dyspepsia * 1    
# participants affected / at risk     2/9325 (0.02%)     0/9319 (0.00%)  
Haemorrhoids * 1    
# participants affected / at risk     0/9325 (0.00%)     2/9319 (0.02%)  
Hiatus hernia * 1    
# participants affected / at risk     1/9325 (0.01%)     1/9319 (0.01%)  
Nausea * 1    
# participants affected / at risk     0/9325 (0.00%)     2/9319 (0.02%)  
Oesophagitis * 1    
# participants affected / at risk     1/9325 (0.01%)     1/9319 (0.01%)  
Ascites * 1    
# participants affected / at risk     1/9325 (0.01%)     0/9319 (0.00%)  
Coeliac disease * 1    
# participants affected / at risk     0/9325 (0.00%)     1/9319 (0.01%)  
Colitis ulcerative * 1    
# participants affected / at risk     1/9325 (0.01%)     0/9319 (0.00%)  
Cyclic vomiting syndrome * 1    
# participants affected / at risk     1/9325 (0.01%)     0/9319 (0.00%)  
Duodenal ulcer * 1    
# participants affected / at risk     0/9325 (0.00%)     1/9319 (0.01%)  
Enteritis * 1    
# participants affected / at risk     0/9325 (0.00%)     1/9319 (0.01%)  
Faecaloma * 1    
# participants affected / at risk     1/9325 (0.01%)     0/9319 (0.00%)  
Faeces hard * 1    
# participants affected / at risk     1/9325 (0.01%)     0/9319 (0.00%)  
Food poisoning * 1    
# participants affected / at risk     1/9325 (0.01%)     0/9319 (0.00%)  
Gastritis erosive * 1    
# participants affected / at risk     0/9325 (0.00%)     1/9319 (0.01%)  
Gastrointestinal inflammation * 1    
# participants affected / at risk     0/9325 (0.00%)     1/9319 (0.01%)  
Ileitis * 1    
# participants affected / at risk     0/9325 (0.00%)     1/9319 (0.01%)  
Ileus * 1    
# participants affected / at risk     1/9325 (0.01%)     0/9319 (0.00%)  
Inflammatory bowel disease * 1    
# participants affected / at risk     0/9325 (0.00%)     1/9319 (0.01%)  
Inguinal hernia * 1    
# participants affected / at risk     0/9325 (0.00%)     1/9319 (0.01%)  
Intestinal mass * 1    
# participants affected / at risk     0/9325 (0.00%)     1/9319 (0.01%)  
Intestinal polyp * 1    
# participants affected / at risk     0/9325 (0.00%)     1/9319 (0.01%)  
Lower gastrointestinal haemorrhage * 1    
# participants affected / at risk     1/9325 (0.01%)     0/9319 (0.00%)  
Malocclusion * 1    
# participants affected / at risk     1/9325 (0.01%)     0/9319 (0.00%)  
Mouth cyst * 1    
# participants affected / at risk     1/9325 (0.01%)     0/9319 (0.00%)  
Pancreatitis acute * 1    
# participants affected / at risk     0/9325 (0.00%)     1/9319 (0.01%)  
Peritonitis * 1    
# participants affected / at risk     1/9325 (0.01%)     0/9319 (0.00%)  
Rectal polyp * 1    
# participants affected / at risk     1/9325 (0.01%)     0/9319 (0.00%)  
Reflux gastritis * 1    
# participants affected / at risk     1/9325 (0.01%)     0/9319 (0.00%)  
Reflux oesophagitis * 1    
# participants affected / at risk     1/9325 (0.01%)     0/9319 (0.00%)  
Tooth malformation * 1    
# participants affected / at risk     0/9325 (0.00%)     1/9319 (0.01%)  
Toothache * 1    
# participants affected / at risk     1/9325 (0.01%)     0/9319 (0.00%)  
Umbilical hernia * 1    
# participants affected / at risk     0/9325 (0.00%)     1/9319 (0.01%)  
General disorders      
Pyrexia * 1    
# participants affected / at risk     1/9325 (0.01%)     2/9319 (0.02%)  
Adverse drug reaction * 1    
# participants affected / at risk     1/9325 (0.01%)     0/9319 (0.00%)  
Chest pain * 1    
# participants affected / at risk     0/9325 (0.00%)     1/9319 (0.01%)  
Cyst * 1    
# participants affected / at risk     1/9325 (0.01%)     0/9319 (0.00%)  
Drowning * 1    
# participants affected / at risk     0/9325 (0.00%)     1/9319 (0.01%)  
Fatigue * 1    
# participants affected / at risk     0/9325 (0.00%)     1/9319 (0.01%)  
Hepatobiliary disorders      
Cholelithiasis * 1    
# participants affected / at risk     9/9325 (0.10%)     14/9319 (0.15%)  
Cholecystitis * 1    
# participants affected / at risk     4/9325 (0.04%)     6/9319 (0.06%)  
Cholecystitis acute * 1    
# participants affected / at risk     4/9325 (0.04%)     2/9319 (0.02%)  
Bile duct stone * 1    
# participants affected / at risk     1/9325 (0.01%)     2/9319 (0.02%)  
Cholecystitis chronic * 1    
# participants affected / at risk     0/9325 (0.00%)     3/9319 (0.03%)  
Biliary colic * 1    
# participants affected / at risk     0/9325 (0.00%)     1/9319 (0.01%)  
Biliary tract disorder * 1    
# participants affected / at risk     1/9325 (0.01%)     0/9319 (0.00%)  
Gallbladder disorder * 1    
# participants affected / at risk     1/9325 (0.01%)     0/9319 (0.00%)  
Gallbladder pain * 1    
# participants affected / at risk     0/9325 (0.00%)     1/9319 (0.01%)  
Gallbladder polyp * 1    
# participants affected / at risk     1/9325 (0.01%)     0/9319 (0.00%)  
Hepatitis alcoholic * 1    
# participants affected / at risk     0/9325 (0.00%)     1/9319 (0.01%)  
Hepatitis cholestatic * 1    
# participants affected / at risk     1/9325 (0.01%)     0/9319 (0.00%)  
Liver disorder * 1    
# participants affected / at risk     1/9325 (0.01%)     0/9319 (0.00%)  
Immune system disorders      
Hypersensitivity * 1    
# participants affected / at risk     5/9325 (0.05%)     2/9319 (0.02%)  
Food allergy * 1    
# participants affected / at risk     1/9325 (0.01%)     2/9319 (0.02%)  
Anaphylactic shock * 1    
# participants affected / at risk     0/9325 (0.00%)     2/9319 (0.02%)  
Anaphylactic reaction * 1    
# participants affected / at risk     1/9325 (0.01%)     0/9319 (0.00%)  
Infections and infestations      
Appendicitis * 1    
# participants affected / at risk     59/9325 (0.63%)     46/9319 (0.49%)  
Pyelonephritis * 1    
# participants affected / at risk     13/9325 (0.14%)     22/9319 (0.24%)  
Pneumonia * 1    
# participants affected / at risk     10/9325 (0.11%)     20/9319 (0.21%)  
Pyelonephritis acute * 1    
# participants affected / at risk     12/9325 (0.13%)     18/9319 (0.19%)  
Gastroenteritis * 1    
# participants affected / at risk     14/9325 (0.15%)     14/9319 (0.15%)  
tonsillitis * 1    
# participants affected / at risk     8/9325 (0.09%)     13/9319 (0.14%)  
Urinary tract infection * 1    
# participants affected / at risk     13/9325 (0.14%)     8/9319 (0.09%)  
Infectious mononucleosis * 1    
# participants affected / at risk     10/9325 (0.11%)     8/9319 (0.09%)  
Pelvic inflammatory disease * 1    
# participants affected / at risk     5/9325 (0.05%)     13/9319 (0.14%)  
Peritonsillar abscess * 1    
# participants affected / at risk     8/9325 (0.09%)     8/9319 (0.09%)  
Acute tonsillitis * 1    
# participants affected / at risk     7/9325 (0.08%)     7/9319 (0.08%)  
Cellulitis * 1    
# participants affected / at risk     7/9325 (0.08%)     2/9319 (0.02%)  
Chronic tonsillitis * 1    
# participants affected / at risk     6/9325 (0.06%)     2/9319 (0.02%)  
Dengue fever * 1    
# participants affected / at risk     3/9325 (0.03%)     3/9319 (0.03%)  
Upper respiratory tract infection * 1    
# participants affected / at risk     3/9325 (0.03%)     3/9319 (0.03%)  
Bronchitis * 1    
# participants affected / at risk     3/9325 (0.03%)     2/9319 (0.02%)  
Endometritis decidual * 1    
# participants affected / at risk     4/9325 (0.04%)     1/9319 (0.01%)  
Erysipelas * 1    
# participants affected / at risk     1/9325 (0.01%)     3/9319 (0.03%)  
Meningitis viral * 1    
# participants affected / at risk     1/9325 (0.01%)     3/9319 (0.03%)  
Appendicitis perforated * 1    
# participants affected / at risk     2/9325 (0.02%)     1/9319 (0.01%)  
Diverticulitis * 1    
# participants affected / at risk     1/9325 (0.01%)     2/9319 (0.02%)  
Genital herpes * 1    
# participants affected / at risk     1/9325 (0.01%)     2/9319 (0.02%)  
Infection * 1    
# participants affected / at risk     0/9325 (0.00%)     3/9319 (0.03%)  
Meningitis tuberculous * 1    
# participants affected / at risk     3/9325 (0.03%)     0/9319 (0.00%)  
Peritonsillitis * 1    
# participants affected / at risk     2/9325 (0.02%)     1/9319 (0.01%)  
Pharyngitis * 1    
# participants affected / at risk     1/9325 (0.01%)     2/9319 (0.02%)  
Pilonidal cyst * 1    
# participants affected / at risk     2/9325 (0.02%)     1/9319 (0.01%)  
Post abortion infection * 1    
# participants affected / at risk     2/9325 (0.02%)     1/9319 (0.01%)  
Post procedural infection * 1    
# participants affected / at risk     2/9325 (0.02%)     1/9319 (0.01%)  
Sinusitis * 1    
# participants affected / at risk     2/9325 (0.02%)     1/9319 (0.01%)  
Viral infection * 1    
# participants affected / at risk     2/9325 (0.02%)     1/9319 (0.01%)  
Abortion infected * 1    
# participants affected / at risk     1/9325 (0.01%)     1/9319 (0.01%)  
Bacterial infection * 1    
# participants affected / at risk     1/9325 (0.01%)     1/9319 (0.01%)  
Bronchopneumonia * 1    
# participants affected / at risk     2/9325 (0.02%)     0/9319 (0.00%)  
Cervicitis * 1    
# participants affected / at risk     1/9325 (0.01%)     1/9319 (0.01%)  
Chronic sinusitis * 1    
# participants affected / at risk     0/9325 (0.00%)     2/9319 (0.02%)  
Ear infection * 1    
# participants affected / at risk     2/9325 (0.02%)     0/9319 (0.00%)  
Endometritis * 1    
# participants affected / at risk     1/9325 (0.01%)     1/9319 (0.01%)  
Epidemic nephropathy * 1    
# participants affected / at risk     1/9325 (0.01%)     1/9319 (0.01%)  
Gastroenteritis viral * 1    
# participants affected / at risk     2/9325 (0.02%)     0/9319 (0.00%)  
Gynaecological chlamydia infection * 1    
# participants affected / at risk     1/9325 (0.01%)     1/9319 (0.01%)  
Hepatitis a * 1    
# participants affected / at risk     0/9325 (0.00%)     2/9319 (0.02%)  
Kidney infection * 1    
# participants affected / at risk     0/9325 (0.00%)     2/9319 (0.02%)  
Mastitis * 1    
# participants affected / at risk     1/9325 (0.01%)     1/9319 (0.01%)  
Parotitis * 1    
# participants affected / at risk     2/9325 (0.02%)     0/9319 (0.00%)  
Pneumonia mycoplasmal * 1    
# participants affected / at risk     1/9325 (0.01%)     1/9319 (0.01%)  
Pulmonary tuberculosis * 1    
# participants affected / at risk     1/9325 (0.01%)     1/9319 (0.01%)  
Salmonellosis * 1    
# participants affected / at risk     1/9325 (0.01%)     1/9319 (0.01%)  
Salpingitis * 1    
# participants affected / at risk     1/9325 (0.01%)     1/9319 (0.01%)  
Salpingo-oophoritis * 1    
# participants affected / at risk     0/9325 (0.00%)     2/9319 (0.02%)  
Tooth abscess * 1    
# participants affected / at risk     1/9325 (0.01%)     1/9319 (0.01%)  
Tooth infection * 1    
# participants affected / at risk     1/9325 (0.01%)     1/9319 (0.01%)  
Tubo-ovarian abscess * 1    
# participants affected / at risk     1/9325 (0.01%)     1/9319 (0.01%)  
Typhoid fever * 1    
# participants affected / at risk     0/9325 (0.00%)     2/9319 (0.02%)  
Varicella * 1    
# participants affected / at risk     1/9325 (0.01%)     1/9319 (0.01%)  
Vulvitis * 1    
# participants affected / at risk     2/9325 (0.02%)     0/9319 (0.00%)  
Wound infection * 1    
# participants affected / at risk     0/9325 (0.00%)     2/9319 (0.02%)  
Abdominal wall abscess * 1    
# participants affected / at risk     0/9325 (0.00%)     1/9319 (0.01%)  
Abscess * 1    
# participants affected / at risk     1/9325 (0.01%)     0/9319 (0.00%)  
Abscess limb * 1    
# participants affected / at risk     0/9325 (0.00%)     1/9319 (0.01%)  
Acquired immunodeficiency syndrome * 1    
# participants affected / at risk     1/9325 (0.01%)     0/9319 (0.00%)  
Acute sinusitis * 1    
# participants affected / at risk     0/9325 (0.00%)     1/9319 (0.01%)  
Appendiceal abscess * 1    
# participants affected / at risk     1/9325 (0.01%)     0/9319 (0.00%)  
Bacterial sepsis * 1    
# participants affected / at risk     0/9325 (0.00%)     1/9319 (0.01%)  
Bacterial toxaemia * 1    
# participants affected / at risk     0/9325 (0.00%)     1/9319 (0.01%)  
Bartholin’s abscess * 1    
# participants affected / at risk     1/9325 (0.01%)     0/9319 (0.00%)  
Beta haemolytic streptococcal infection * 1    
# participants affected / at risk     0/9325 (0.00%)     1/9319 (0.01%)  
Bone tuberculosis * 1    
# participants affected / at risk     1/9325 (0.01%)     0/9319 (0.00%)  
Breast abscess * 1    
# participants affected / at risk     0/9325 (0.00%)     1/9319 (0.01%)  
Carbuncle * 1    
# participants affected / at risk     1/9325 (0.01%)     0/9319 (0.00%)  
Cerebral toxoplasmosis * 1    
# participants affected / at risk     1/9325 (0.01%)     0/9319 (0.00%)  
Cystitis * 1    
# participants affected / at risk     0/9325 (0.00%)     1/9319 (0.01%)  
Cytomegalovirus infection * 1    
# participants affected / at risk     1/9325 (0.01%)     0/9319 (0.00%)  
Enteritis infectious * 1    
# participants affected / at risk     0/9325 (0.00%)     1/9319 (0.01%)  
Epiglottitis * 1    
# participants affected / at risk     1/9325 (0.01%)     0/9319 (0.00%)  
Epstein-barr virus infection * 1    
# participants affected / at risk     1/9325 (0.01%)     0/9319 (0.00%)  
Escherichia sepsis * 1    
# participants affected / at risk     0/9325 (0.00%)     1/9319 (0.01%)  
Extrapulmonary tuberculosis * 1    
# participants affected / at risk     0/9325 (0.00%)     1/9319 (0.01%)  
Eye infection toxoplasmal * 1    
# participants affected / at risk     0/9325 (0.00%)     1/9319 (0.01%)  
Gastroenteritis bacterial * 1    
# participants affected / at risk     1/9325 (0.01%)     0/9319 (0.00%)  
Gastrointestinal infection * 1    
# participants affected / at risk     0/9325 (0.00%)     1/9319 (0.01%)  
Haemorrhagic fever * 1    
# participants affected / at risk     1/9325 (0.01%)     0/9319 (0.00%)  
Hepatitis c * 1    
# participants affected / at risk     0/9325 (0.00%)     1/9319 (0.01%)  
Herpes oesophagitis * 1    
# participants affected / at risk     1/9325 (0.01%)     0/9319 (0.00%)  
Hordeolum * 1    
# participants affected / at risk     1/9325 (0.01%)     0/9319 (0.00%)  
Induced abortion infection * 1    
# participants affected / at risk     1/9325 (0.01%)     0/9319 (0.00%)  
Infected bites * 1    
# participants affected / at risk     1/9325 (0.01%)     0/9319 (0.00%)  
Infection parasitic * 1    
# participants affected / at risk     1/9325 (0.01%)     0/9319 (0.00%)  
Laryngitis * 1    
# participants affected / at risk     1/9325 (0.01%)     0/9319 (0.00%)  
Lobar pneumonia * 1    
# participants affected / at risk     1/9325 (0.01%)     0/9319 (0.00%)  
Meningitis bacterial * 1    
# participants affected / at risk     0/9325 (0.00%)     1/9319 (0.01%)  
Meningitis pneumococcal * 1    
# participants affected / at risk     0/9325 (0.00%)     1/9319 (0.01%)  
Neuroborreliosis * 1    
# participants affected / at risk     1/9325 (0.01%)     0/9319 (0.00%)  
Osteomyelitis * 1    
# participants affected / at risk     0/9325 (0.00%)     1/9319 (0.01%)  
Otitis media acute * 1    
# participants affected / at risk     1/9325 (0.01%)     0/9319 (0.00%)  
Ovarian abscess * 1    
# participants affected / at risk     0/9325 (0.00%)     1/9319 (0.01%)  
Parotid abscess * 1    
# participants affected / at risk     1/9325 (0.01%)     0/9319 (0.00%)  
Periorbital cellulitis * 1    
# participants affected / at risk     1/9325 (0.01%)     0/9319 (0.00%)  
Peritoneal tuberculosis * 1    
# participants affected / at risk     1/9325 (0.01%)     0/9319 (0.00%)  
Pneumococcal sepsis * 1    
# participants affected / at risk     0/9325 (0.00%)     1/9319 (0.01%)  
Pneumonia bacterial * 1    
# participants affected / at risk     1/9325 (0.01%)     0/9319 (0.00%)  
Pyoderma * 1    
# participants affected / at risk     1/9325 (0.01%)     0/9319 (0.00%)  
Respiratory tract infection * 1    
# participants affected / at risk     0/9325 (0.00%)     1/9319 (0.01%)  
Rhinitis * 1    
# participants affected / at risk     0/9325 (0.00%)     1/9319 (0.01%)  
Sepsis * 1    
# participants affected / at risk     0/9325 (0.00%)     1/9319 (0.01%)  
Skin infection * 1    
# participants affected / at risk     0/9325 (0.00%)     1/9319 (0.01%)  
Streptococcal infection * 1    
# participants affected / at risk     0/9325 (0.00%)     1/9319 (0.01%)  
Subcutaneous abscess * 1    
# participants affected / at risk     0/9325 (0.00%)     1/9319 (0.01%)  
Sweat gland infection * 1    
# participants affected / at risk     0/9325 (0.00%)     1/9319 (0.01%)  
Tonsillitis streptococcal * 1    
# participants affected / at risk     1/9325 (0.01%)     0/9319 (0.00%)  
Trichomoniasis * 1    
# participants affected / at risk     0/9325 (0.00%)     1/9319 (0.01%)  
Tuberculosis * 1    
# participants affected / at risk     0/9325 (0.00%)     1/9319 (0.01%)  
Urinary tract infection bacterial * 1    
# participants affected / at risk     1/9325 (0.01%)     0/9319 (0.00%)  
Vulval abscess * 1    
# participants affected / at risk     0/9325 (0.00%)     1/9319 (0.01%)  
Injury, poisoning and procedural complications      
Road traffic accident * 1    
# participants affected / at risk     10/9325 (0.11%)     9/9319 (0.10%)  
Concussion * 1    
# participants affected / at risk     6/9325 (0.06%)     7/9319 (0.08%)  
Ligament rupture * 1    
# participants affected / at risk     10/9325 (0.11%)     3/9319 (0.03%)  
Ankle fracture * 1    
# participants affected / at risk     7/9325 (0.08%)     2/9319 (0.02%)  
Joint dislocation * 1    
# participants affected / at risk     7/9325 (0.08%)     2/9319 (0.02%)  
Post procedural haemorrhage * 1    
# participants affected / at risk     4/9325 (0.04%)     5/9319 (0.05%)  
Wrist fracture * 1    
# participants affected / at risk     6/9325 (0.06%)     2/9319 (0.02%)  
Contusion * 1    
# participants affected / at risk     3/9325 (0.03%)     4/9319 (0.04%)  
Foot fracture * 1    
# participants affected / at risk     4/9325 (0.04%)     3/9319 (0.03%)  
Head injury * 1    
# participants affected / at risk     4/9325 (0.04%)     3/9319 (0.03%)  
Clavicle fracture * 1    
# participants affected / at risk     2/9325 (0.02%)     4/9319 (0.04%)  
Overdose * 1    
# participants affected / at risk     3/9325 (0.03%)     3/9319 (0.03%)  
Radius fracture * 1    
# participants affected / at risk     3/9325 (0.03%)     2/9319 (0.02%)  
Humerus fracture * 1    
# participants affected / at risk     1/9325 (0.01%)     3/9319 (0.03%)  
Limb injury * 1    
# participants affected / at risk     2/9325 (0.02%)     2/9319 (0.02%)  
Multiple fractures * 1    
# participants affected / at risk     2/9325 (0.02%)     2/9319 (0.02%)  
Tibia fracture * 1    
# participants affected / at risk     2/9325 (0.02%)     2/9319 (0.02%)  
Hand fracture * 1    
# participants affected / at risk     2/9325 (0.02%)     1/9319 (0.01%)  
Lower limb fracture * 1    
# participants affected / at risk     3/9325 (0.03%)     0/9319 (0.00%)  
Meniscus lesion * 1    
# participants affected / at risk     3/9325 (0.03%)     0/9319 (0.00%)  
Multiple injuries * 1    
# participants affected / at risk     0/9325 (0.00%)     3/9319 (0.03%)  
Thermal burn * 1    
# participants affected / at risk     2/9325 (0.02%)     1/9319 (0.01%)  
Upper limb fracture * 1    
# participants affected / at risk     1/9325 (0.01%)     2/9319 (0.02%)  
Abortion induced incomplete * 1    
# participants affected / at risk     2/9325 (0.02%)     0/9319 (0.00%)  
Accidental needle stick * 1    
# participants affected / at risk     1/9325 (0.01%)     1/9319 (0.01%)  
Accidental overdose * 1    
# participants affected / at risk     2/9325 (0.02%)     0/9319 (0.00%)  
Alcohol poisoning * 1    
# participants affected / at risk     1/9325 (0.01%)     1/9319 (0.01%)  
Brain contusion * 1    
# participants affected / at risk     1/9325 (0.01%)     1/9319 (0.01%)  
Excoriation * 1    
# participants affected / at risk     1/9325 (0.01%)     1/9319 (0.01%)  
Facial bones fracture * 1    
# participants affected / at risk     1/9325 (0.01%)     1/9319 (0.01%)  
Femur fracture * 1    
# participants affected / at risk     1/9325 (0.01%)     1/9319 (0.01%)  
Fibula fracture * 1    
# participants affected / at risk     2/9325 (0.02%)     0/9319 (0.00%)  
Gun shot wound * 1    
# participants affected / at risk     0/9325 (0.00%)     2/9319 (0.02%)  
Injury * 1    
# participants affected / at risk     0/9325 (0.00%)     2/9319 (0.02%)  
Jaw fracture * 1    
# participants affected / at risk     0/9325 (0.00%)     2/9319 (0.02%)  
Muscle strain * 1    
# participants affected / at risk     0/9325 (0.00%)     2/9319 (0.02%)  
Pelvic fracture * 1    
# participants affected / at risk     1/9325 (0.01%)     1/9319 (0.01%)  
Skin laceration * 1    
# participants affected / at risk     1/9325 (0.01%)     1/9319 (0.01%)  
Spinal compression fracture * 1    
# participants affected / at risk     1/9325 (0.01%)     1/9319 (0.01%)  
Ulna fracture * 1    
# participants affected / at risk     1/9325 (0.01%)     1/9319 (0.01%)  
Abortion induced complete complicated * 1    
# participants affected / at risk     0/9325 (0.00%)     1/9319 (0.01%)  
Accident * 1    
# participants affected / at risk     1/9325 (0.01%)     0/9319 (0.00%)  
Animal bite * 1    
# participants affected / at risk     0/9325 (0.00%)     1/9319 (0.01%)  
Arterial injury * 1    
# participants affected / at risk     0/9325 (0.00%)     1/9319 (0.01%)  
Arthropod bite * 1    
# participants affected / at risk     1/9325 (0.01%)     0/9319 (0.00%)  
Bone fissure * 1    
# participants affected / at risk     1/9325 (0.01%)     0/9319 (0.00%)  
Burns second degree * 1    
# participants affected / at risk     0/9325 (0.00%)     1/9319 (0.01%)  
Cartilage injury * 1    
# participants affected / at risk     0/9325 (0.00%)     1/9319 (0.01%)  
Colon injury * 1    
# participants affected / at risk     0/9325 (0.00%)     1/9319 (0.01%)  
Device occlusion * 1    
# participants affected / at risk     1/9325 (0.01%)     0/9319 (0.00%)  
Diaphragmatic injury * 1    
# participants affected / at risk     0/9325 (0.00%)     1/9319 (0.01%)  
Fracture * 1    
# participants affected / at risk     1/9325 (0.01%)     0/9319 (0.00%)  
Ilium fracture * 1    
# participants affected / at risk     1/9325 (0.01%)     0/9319 (0.00%)  
Joint injury * 1    
# participants affected / at risk     1/9325 (0.01%)     0/9319 (0.00%)  
Joint sprain * 1    
# participants affected / at risk     1/9325 (0.01%)     0/9319 (0.00%)  
Lumbar vertebral fracture * 1    
# participants affected / at risk     1/9325 (0.01%)     0/9319 (0.00%)  
Muscle injury * 1    
# participants affected / at risk     0/9325 (0.00%)     1/9319 (0.01%)  
Nerve injury * 1    
# participants affected / at risk     0/9325 (0.00%)     1/9319 (0.01%)  
Poisoning * 1    
# participants affected / at risk     1/9325 (0.01%)     0/9319 (0.00%)  
Post lumbar puncture syndrome * 1    
# participants affected / at risk     0/9325 (0.00%)     1/9319 (0.01%)  
Post procedural haematoma * 1    
# participants affected / at risk     0/9325 (0.00%)     1/9319 (0.01%)  
Procedural pain * 1    
# participants affected / at risk     1/9325 (0.01%)     0/9319 (0.00%)  
Rib fracture * 1    
# participants affected / at risk     0/9325 (0.00%)     1/9319 (0.01%)  
Scapula fracture * 1    
# participants affected / at risk     1/9325 (0.01%)     0/9319 (0.00%)  
Skeletal injury * 1    
# participants affected / at risk     0/9325 (0.00%)     1/9319 (0.01%)  
Skull fracture * 1    
# participants affected / at risk     0/9325 (0.00%)     1/9319 (0.01%)  
Snake bite * 1    
# participants affected / at risk     0/9325 (0.00%)     1/9319 (0.01%)  
Soft tissue injury * 1    
# participants affected / at risk     0/9325 (0.00%)     1/9319 (0.01%)  
Spinal fracture * 1    
# participants affected / at risk     1/9325 (0.01%)     0/9319 (0.00%)  
Splenic rupture * 1    
# participants affected / at risk     1/9325 (0.01%)     0/9319 (0.00%)  
Tendon injury * 1    
# participants affected / at risk     0/9325 (0.00%)     1/9319 (0.01%)  
Tendon rupture * 1    
# participants affected / at risk     1/9325 (0.01%)     0/9319 (0.00%)  
Thoracic vertebral fracture * 1    
# participants affected / at risk     0/9325 (0.00%)     1/9319 (0.01%)  
Traumatic liver injury * 1    
# participants affected / at risk     0/9325 (0.00%)     1/9319 (0.01%)  
Ulnar nerve injury * 1    
# participants affected / at risk     1/9325 (0.01%)     0/9319 (0.00%)  
Uterine perforation * 1    
# participants affected / at risk     1/9325 (0.01%)     0/9319 (0.00%)  
Uterine rupture * 1    
# participants affected / at risk     0/9325 (0.00%)     1/9319 (0.01%)  
Whiplash injury * 1    
# participants affected / at risk     1/9325 (0.01%)     0/9319 (0.00%)  
Investigations      
Weight increased * 1    
# participants affected / at risk     1/9325 (0.01%)     0/9319 (0.00%)  
Metabolism and nutrition disorders      
Dehydration * 1    
# participants affected / at risk     1/9325 (0.01%)     4/9319 (0.04%)  
Gestational diabetes * 1    
# participants affected / at risk     1/9325 (0.01%)     1/9319 (0.01%)  
Hypokalaemia * 1    
# participants affected / at risk     1/9325 (0.01%)     1/9319 (0.01%)  
Decreased appetite * 1    
# participants affected / at risk     1/9325 (0.01%)     0/9319 (0.00%)  
Diabetes mellitus * 1    
# participants affected / at risk     0/9325 (0.00%)     1/9319 (0.01%)  
Diabetic ketoacidosis * 1    
# participants affected / at risk     1/9325 (0.01%)     0/9319 (0.00%)  
Hypoglycaemia * 1    
# participants affected / at risk     1/9325 (0.01%)     0/9319 (0.00%)  
obesity * 1    
# participants affected / at risk     0/9325 (0.00%)     1/9319 (0.01%)  
Type 2 diabetes mellitus * 1    
# participants affected / at risk     0/9325 (0.00%)     1/9319 (0.01%)  
Musculoskeletal and connective tissue disorders      
Back pain * 1    
# participants affected / at risk     3/9325 (0.03%)     6/9319 (0.06%)  
Intervertebral disc protrusion * 1    
# participants affected / at risk     4/9325 (0.04%)     3/9319 (0.03%)  
Systemic lupus erythematosus * 1    
# participants affected / at risk     0/9325 (0.00%)     3/9319 (0.03%)  
Bone cyst * 1    
# participants affected / at risk     1/9325 (0.01%)     1/9319 (0.01%)  
Foot deformity * 1    
# participants affected / at risk     0/9325 (0.00%)     2/9319 (0.02%)  
Rheumatoid arthritis * 1    
# participants affected / at risk     1/9325 (0.01%)     1/9319 (0.01%)  
Arthritis * 1    
# participants affected / at risk     1/9325 (0.01%)     0/9319 (0.00%)  
Arthritis reactive * 1    
# participants affected / at risk     0/9325 (0.00%)     1/9319 (0.01%)  
Arthropathy * 1    
# participants affected / at risk     0/9325 (0.00%)     1/9319 (0.01%)  
Ligament disorder * 1    
# participants affected / at risk     0/9325 (0.00%)     1/9319 (0.01%)  
Musculoskeletal pain * 1    
# participants affected / at risk     1/9325 (0.01%)     0/9319 (0.00%)  
Myofascial pain syndrome * 1    
# participants affected / at risk     1/9325 (0.01%)     0/9319 (0.00%)  
Osteoarthritis * 1    
# participants affected / at risk     1/9325 (0.01%)     0/9319 (0.00%)  
Pain in extremity * 1    
# participants affected / at risk     0/9325 (0.00%)     1/9319 (0.01%)  
Psoriatic arthropathy * 1    
# participants affected / at risk     1/9325 (0.01%)     0/9319 (0.00%)  
Synovitis * 1    
# participants affected / at risk     0/9325 (0.00%)     1/9319 (0.01%)  
Neoplasms benign, malignant and unspecified (incl cysts and polyps)      
Uterine leiomyoma * 1    
# participants affected / at risk     6/9325 (0.06%)     1/9319 (0.01%)  
Ovarian germ cell teratoma benign * 1    
# participants affected / at risk     3/9325 (0.03%)     3/9319 (0.03%)  
Teratoma * 1    
# participants affected / at risk     2/9325 (0.02%)     3/9319 (0.03%)  
Benign hydatidiform mole * 1    
# participants affected / at risk     1/9325 (0.01%)     3/9319 (0.03%)  
Malignant melanoma * 1    
# participants affected / at risk     1/9325 (0.01%)     2/9319 (0.02%)  
Ovarian adenoma * 1    
# participants affected / at risk     1/9325 (0.01%)     2/9319 (0.02%)  
Fibroadenoma of breast * 1    
# participants affected / at risk     2/9325 (0.02%)     0/9319 (0.00%)  
Thyroid cancer * 1    
# participants affected / at risk     1/9325 (0.01%)     1/9319 (0.01%)  
Astrocytoma malignant * 1    
# participants affected / at risk     0/9325 (0.00%)     1/9319 (0.01%)  
Astrocytoma, low grade * 1    
# participants affected / at risk     1/9325 (0.01%)     0/9319 (0.00%)  
Basal cell carcinoma * 1    
# participants affected / at risk     0/9325 (0.00%)     1/9319 (0.01%)  
Bone sarcoma * 1    
# participants affected / at risk     1/9325 (0.01%)     0/9319 (0.00%)  
Carcinoid tumour of the appendix * 1    
# participants affected / at risk     1/9325 (0.01%)     0/9319 (0.00%)  
Gestational trophoblastic tumour * 1    
# participants affected / at risk     0/9325 (0.00%)     1/9319 (0.01%)  
Leiomyoma * 1    
# participants affected / at risk     1/9325 (0.01%)     0/9319 (0.00%)  
Metastases to lung * 1    
# participants affected / at risk     0/9325 (0.00%)     1/9319 (0.01%)  
Neoplasm * 1    
# participants affected / at risk     0/9325 (0.00%)     1/9319 (0.01%)  
Ovarian neoplasm * 1    
# participants affected / at risk     1/9325 (0.01%)     0/9319 (0.00%)  
Thyroid neoplasm * 1    
# participants affected / at risk     0/9325 (0.00%)     1/9319 (0.01%)  
Vulval cancer * 1    
# participants affected / at risk     0/9325 (0.00%)     1/9319 (0.01%)  
Nervous system disorders      
Epilepsy * 1    
# participants affected / at risk     3/9325 (0.03%)     3/9319 (0.03%)  
Headache * 1    
# participants affected / at risk     1/9325 (0.01%)     5/9319 (0.05%)  
Migraine * 1    
# participants affected / at risk     2/9325 (0.02%)     4/9319 (0.04%)  
Multiple sclerosis * 1    
# participants affected / at risk     1/9325 (0.01%)     3/9319 (0.03%)  
Optic neuritis * 1    
# participants affected / at risk     1/9325 (0.01%)     3/9319 (0.03%)  
Cerebrovascular accident * 1    
# participants affected / at risk     2/9325 (0.02%)     1/9319 (0.01%)  
Convulsion * 1    
# participants affected / at risk     0/9325 (0.00%)     3/9319 (0.03%)  
Facial palsy * 1    
# participants affected / at risk     1/9325 (0.01%)     2/9319 (0.02%)  
Cerebral haemorrhage * 1    
# participants affected / at risk     1/9325 (0.01%)     1/9319 (0.01%)  
Dizziness * 1    
# participants affected / at risk     0/9325 (0.00%)     2/9319 (0.02%)  
Grand mal convulsion * 1    
# participants affected / at risk     0/9325 (0.00%)     2/9319 (0.02%)  
Paraesthesia * 1    
# participants affected / at risk     1/9325 (0.01%)     1/9319 (0.01%)  
Subarachnoid haemorrhage * 1    
# participants affected / at risk     1/9325 (0.01%)     1/9319 (0.01%)  
Syncope * 1    
# participants affected / at risk     2/9325 (0.02%)     0/9319 (0.00%)  
Anoxic encephalopathy * 1    
# participants affected / at risk     0/9325 (0.00%)     1/9319 (0.01%)  
Aphasia * 1    
# participants affected / at risk     0/9325 (0.00%)     1/9319 (0.01%)  
Benign intracranial hypertension * 1    
# participants affected / at risk     1/9325 (0.01%)     0/9319 (0.00%)  
Brain injury * 1    
# participants affected / at risk     1/9325 (0.01%)     0/9319 (0.00%)  
Cubital tunnel syndrome * 1    
# participants affected / at risk     0/9325 (0.00%)     1/9319 (0.01%)  
Dystonia * 1    
# participants affected / at risk     0/9325 (0.00%)     1/9319 (0.01%)  
Facial paresis * 1    
# participants affected / at risk     0/9325 (0.00%)     1/9319 (0.01%)  
Hydrocephalus * 1    
# participants affected / at risk     1/9325 (0.01%)     0/9319 (0.00%)  
Intracranial aneurysm * 1    
# participants affected / at risk     1/9325 (0.01%)     0/9319 (0.00%)  
Intracranial venous sinus thrombosis * 1    
# participants affected / at risk     0/9325 (0.00%)     1/9319 (0.01%)  
Migraine with aura * 1    
# participants affected / at risk     1/9325 (0.01%)     0/9319 (0.00%)  
Neuropathy peripheral * 1    
# participants affected / at risk     1/9325 (0.01%)     0/9319 (0.00%)  
Peroneal nerve palsy * 1    
# participants affected / at risk     1/9325 (0.01%)     0/9319 (0.00%)  
Pleocytosis * 1    
# participants affected / at risk     1/9325 (0.01%)     0/9319 (0.00%)  
Polyneuropathy * 1    
# participants affected / at risk     0/9325 (0.00%)     1/9319 (0.01%)  
Sciatica * 1    
# participants affected / at risk     1/9325 (0.01%)     0/9319 (0.00%)  
Tension headache * 1    
# participants affected / at risk     0/9325 (0.00%)     1/9319 (0.01%)  
Pregnancy, puerperium and perinatal conditions      
Abortion spontaneous * 1    
# participants affected / at risk     59/9325 (0.63%)     70/9319 (0.75%)  
Abortion spontaneous incomplete * 1    
# participants affected / at risk     40/9325 (0.43%)     54/9319 (0.58%)  
Abortion spontaneous complete * 1    
# participants affected / at risk     46/9325 (0.49%)     43/9319 (0.46%)  
Abortion missed * 1    
# participants affected / at risk     27/9325 (0.29%)     20/9319 (0.21%)  
Premature labour * 1    
# participants affected / at risk     12/9325 (0.13%)     21/9319 (0.23%)  
Ectopic pregnancy * 1    
# participants affected / at risk     8/9325 (0.09%)     18/9319 (0.19%)  
Pre-eclampsia * 1    
# participants affected / at risk     11/9325 (0.12%)     10/9319 (0.11%)  
Blighted ovum * 1    
# participants affected / at risk     9/9325 (0.10%)     10/9319 (0.11%)  
Intra-uterine death * 1    
# participants affected / at risk     7/9325 (0.08%)     9/9319 (0.10%)  
Stillbirth * 1    
# participants affected / at risk     7/9325 (0.08%)     8/9319 (0.09%)  
Hyperemesis gravidarum * 1    
# participants affected / at risk     4/9325 (0.04%)     5/9319 (0.05%)  
Premature rupture of membranes * 1    
# participants affected / at risk     3/9325 (0.03%)     6/9319 (0.06%)  
Pregnancy induced hypertension * 1    
# participants affected / at risk     5/9325 (0.05%)     2/9319 (0.02%)  
Abortion threatened * 1    
# participants affected / at risk     2/9325 (0.02%)     3/9319 (0.03%)  
Premature baby * 1    
# participants affected / at risk     2/9325 (0.02%)     3/9319 (0.03%)  
Premature separation of placenta * 1    
# participants affected / at risk     1/9325 (0.01%)     4/9319 (0.04%)  
Chorioamnionitis * 1    
# participants affected / at risk     1/9325 (0.01%)     3/9319 (0.03%)  
Abortion incomplete * 1    
# participants affected / at risk     3/9325 (0.03%)     0/9319 (0.00%)  
Eclampsia * 1    
# participants affected / at risk     2/9325 (0.02%)     1/9319 (0.01%)  
Retained products of conception * 1    
# participants affected / at risk     1/9325 (0.01%)     2/9319 (0.02%)  
Ruptured ectopic pregnancy * 1    
# participants affected / at risk     1/9325 (0.01%)     2/9319 (0.02%)  
Threatened labour * 1    
# participants affected / at risk     3/9325 (0.03%)     0/9319 (0.00%)  
Breech presentation * 1    
# participants affected / at risk     1/9325 (0.01%)     1/9319 (0.01%)  
Placenta praevia * 1    
# participants affected / at risk     2/9325 (0.02%)     0/9319 (0.00%)  
Retained placenta or membranes * 1    
# participants affected / at risk     0/9325 (0.00%)     2/9319 (0.02%)  
Abortion complete * 1    
# participants affected / at risk     0/9325 (0.00%)     1/9319 (0.01%)  
Antepartum haemorrhage * 1    
# participants affected / at risk     0/9325 (0.00%)     1/9319 (0.01%)  
Arrested labour * 1    
# participants affected / at risk     1/9325 (0.01%)     0/9319 (0.00%)  
Cephalo-pelvic disproportion * 1    
# participants affected / at risk     0/9325 (0.00%)     1/9319 (0.01%)  
Face presentation * 1    
# participants affected / at risk     0/9325 (0.00%)     1/9319 (0.01%)  
False labour * 1    
# participants affected / at risk     1/9325 (0.01%)     0/9319 (0.00%)  
Foetal distress syndrome * 1    
# participants affected / at risk     0/9325 (0.00%)     1/9319 (0.01%)  
Foetal growth retardation * 1    
# participants affected / at risk     0/9325 (0.00%)     1/9319 (0.01%)  
Imminent abortion * 1    
# participants affected / at risk     1/9325 (0.01%)     0/9319 (0.00%)  
Induced labour * 1    
# participants affected / at risk     0/9325 (0.00%)     1/9319 (0.01%)  
Obstructed labour * 1    
# participants affected / at risk     0/9325 (0.00%)     1/9319 (0.01%)  
Oligohydramnios * 1    
# participants affected / at risk     0/9325 (0.00%)     1/9319 (0.01%)  
Placenta accreta * 1    
# participants affected / at risk     1/9325 (0.01%)     0/9319 (0.00%)  
Placenta praevia haemorrhage * 1    
# participants affected / at risk     1/9325 (0.01%)     0/9319 (0.00%)  
Postpartum uterine subinvolution * 1    
# participants affected / at risk     1/9325 (0.01%)     0/9319 (0.00%)  
Prolonged labour * 1    
# participants affected / at risk     1/9325 (0.01%)     0/9319 (0.00%)  
Small for dates baby * 1    
# participants affected / at risk     1/9325 (0.01%)     0/9319 (0.00%)  
Uterine inversion * 1    
# participants affected / at risk     1/9325 (0.01%)     0/9319 (0.00%)  
Psychiatric disorders      
Depression * 1    
# participants affected / at risk     19/9325 (0.20%)     20/9319 (0.21%)  
Suicide attempt * 1    
# participants affected / at risk     11/9325 (0.12%)     9/9319 (0.10%)  
Bipolar disorder * 1    
# participants affected / at risk     3/9325 (0.03%)     3/9319 (0.03%)  
Major depression * 1    
# participants affected / at risk     5/9325 (0.05%)     1/9319 (0.01%)  
Psychotic disorder * 1    
# participants affected / at risk     3/9325 (0.03%)     2/9319 (0.02%)  
Panic disorder * 1    
# participants affected / at risk     1/9325 (0.01%)     3/9319 (0.03%)  
Anorexia nervosa * 1    
# participants affected / at risk     0/9325 (0.00%)     3/9319 (0.03%)  
Completed suicide * 1    
# participants affected / at risk     3/9325 (0.03%)     0/9319 (0.00%)  
Drug dependence * 1    
# participants affected / at risk     1/9325 (0.01%)     2/9319 (0.02%)  
Alcoholism * 1    
# participants affected / at risk     0/9325 (0.00%)     2/9319 (0.02%)  
Anxiety * 1    
# participants affected / at risk     1/9325 (0.01%)     1/9319 (0.01%)  
Bipolar disorder * 1    
# participants affected / at risk     1/9325 (0.01%)     1/9319 (0.01%)  
Conversion disorder * 1    
# participants affected / at risk     0/9325 (0.00%)     2/9319 (0.02%)  
Eating disorder * 1    
# participants affected / at risk     2/9325 (0.02%)     0/9319 (0.00%)  
Abnormal behaviour * 1    
# participants affected / at risk     0/9325 (0.00%)     1/9319 (0.01%)  
Alcohol abuse * 1    
# participants affected / at risk     1/9325 (0.01%)     0/9319 (0.00%)  
Bipolar ii disorder * 1    
# participants affected / at risk     0/9325 (0.00%)     1/9319 (0.01%)  
Bulimia nervosa * 1    
# participants affected / at risk     0/9325 (0.00%)     1/9319 (0.01%)  
Confusional state * 1    
# participants affected / at risk     1/9325 (0.01%)     0/9319 (0.00%)  
Depression suicidal * 1    
# participants affected / at risk     1/9325 (0.01%)     0/9319 (0.00%)  
Dissociative disorder * 1    
# participants affected / at risk     0/9325 (0.00%)     1/9319 (0.01%)  
Drug abuse * 1    
# participants affected / at risk     1/9325 (0.01%)     0/9319 (0.00%)  
Dysthymic disorder * 1    
# participants affected / at risk     0/9325 (0.00%)     1/9319 (0.01%)  
Emotional distress * 1    
# participants affected / at risk     1/9325 (0.01%)     0/9319 (0.00%)  
Generalized anxiety disorder * 1    
# participants affected / at risk     1/9325 (0.01%)     0/9319 (0.00%)  
Histrionic personality disorder * 1    
# participants affected / at risk     0/9325 (0.00%)     1/9319 (0.01%)  
Intentional self-injury * 1    
# participants affected / at risk     1/9325 (0.01%)     0/9319 (0.00%)  
Mania * 1    
# participants affected / at risk     1/9325 (0.01%)     0/9319 (0.00%)  
Mental disorder * 1    
# participants affected / at risk     1/9325 (0.01%)     0/9319 (0.00%)  
Panic reaction * 1    
# participants affected / at risk     1/9325 (0.01%)     0/9319 (0.00%)  
Postpartum depression * 1    
# participants affected / at risk     0/9325 (0.00%)     1/9319 (0.01%)  
Schizophrenia * 1    
# participants affected / at risk     1/9325 (0.01%)     0/9319 (0.00%)  
Renal and urinary disorders      
Nephrolithiasis * 1    
# participants affected / at risk     1/9325 (0.01%)     2/9319 (0.02%)  
Calculus bladder * 1    
# participants affected / at risk     0/9325 (0.00%)     2/9319 (0.02%)  
Calculus ureteric * 1    
# participants affected / at risk     1/9325 (0.01%)     0/9319 (0.00%)  
Calculus urinary * 1    
# participants affected / at risk     1/9325 (0.01%)     0/9319 (0.00%)  
Glomerulonephritis acute * 1    
# participants affected / at risk     0/9325 (0.00%)     1/9319 (0.01%)  
Glomerulonephritis membranoproliferative * 1    
# participants affected / at risk     0/9325 (0.00%)     1/9319 (0.01%)  
Hydronephrosis * 1    
# participants affected / at risk     1/9325 (0.01%)     0/9319 (0.00%)  
Nephritis * 1    
# participants affected / at risk     1/9325 (0.01%)     0/9319 (0.00%)  
Nephrotic syndrome * 1    
# participants affected / at risk     1/9325 (0.01%)     0/9319 (0.00%)  
Renal failure * 1    
# participants affected / at risk     1/9325 (0.01%)     0/9319 (0.00%)  
Renal failure acute * 1    
# participants affected / at risk     0/9325 (0.00%)     1/9319 (0.01%)  
Urinary retention * 1    
# participants affected / at risk     1/9325 (0.01%)     0/9319 (0.00%)  
Reproductive system and breast disorders      
Ovarian cyst * 1    
# participants affected / at risk     10/9325 (0.11%)     11/9319 (0.12%)  
Ovarian cyst ruptured * 1    
# participants affected / at risk     11/9325 (0.12%)     4/9319 (0.04%)  
Endometriosis * 1    
# participants affected / at risk     6/9325 (0.06%)     2/9319 (0.02%)  
Cervical dysplasia * 1    
# participants affected / at risk     1/9325 (0.01%)     4/9319 (0.04%)  
Bartholinitis * 1    
# participants affected / at risk     2/9325 (0.02%)     2/9319 (0.02%)  
Haemorrhagic ovarian cyst * 1    
# participants affected / at risk     1/9325 (0.01%)     3/9319 (0.03%)  
Dysfunctional uterine bleeding * 1    
# participants affected / at risk     1/9325 (0.01%)     2/9319 (0.02%)  
Fallopian tube cyst * 1    
# participants affected / at risk     0/9325 (0.00%)     3/9319 (0.03%)  
Ovarian cyst torsion * 1    
# participants affected / at risk     2/9325 (0.02%)     1/9319 (0.01%)  
Dysmenorrhoea * 1    
# participants affected / at risk     1/9325 (0.01%)     1/9319 (0.01%)  
Parovarian cyst * 1    
# participants affected / at risk     1/9325 (0.01%)     1/9319 (0.01%)  
Vaginal haemorrhage * 1    
# participants affected / at risk     2/9325 (0.02%)     0/9319 (0.00%)  
Bartholin’s cyst * 1    
# participants affected / at risk     1/9325 (0.01%)     0/9319 (0.00%)  
Dyspareunia * 1    
# participants affected / at risk     1/9325 (0.01%)     0/9319 (0.00%)  
Ovarian adhesion * 1    
# participants affected / at risk     1/9325 (0.01%)     0/9319 (0.00%)  
Ovarian torsion * 1    
# participants affected / at risk     0/9325 (0.00%)     1/9319 (0.01%)  
Pelvic pain * 1    
# participants affected / at risk     0/9325 (0.00%)     1/9319 (0.01%)  
Polycystic ovaries * 1    
# participants affected / at risk     0/9325 (0.00%)     1/9319 (0.01%)  
Uterine atony * 1    
# participants affected / at risk     0/9325 (0.00%)     1/9319 (0.01%)  
Uterine malposition * 1    
# participants affected / at risk     0/9325 (0.00%)     1/9319 (0.01%)  
Uterine polyp * 1    
# participants affected / at risk     1/9325 (0.01%)     0/9319 (0.00%)  
Respiratory, thoracic and mediastinal disorders      
Asthma * 1    
# participants affected / at risk     8/9325 (0.09%)     8/9319 (0.09%)  
Nasal septum deviation * 1    
# participants affected / at risk     2/9325 (0.02%)     2/9319 (0.02%)  
Pulmonary embolism * 1    
# participants affected / at risk     0/9325 (0.00%)     3/9319 (0.03%)  
Tonsillar hypertrophy * 1    
# participants affected / at risk     2/9325 (0.02%)     1/9319 (0.01%)  
Pleural effusion * 1    
# participants affected / at risk     0/9325 (0.00%)     2/9319 (0.02%)  
Apnoeic attack * 1    
# participants affected / at risk     1/9325 (0.01%)     0/9319 (0.00%)  
Dyspnoea * 1    
# participants affected / at risk     0/9325 (0.00%)     1/9319 (0.01%)  
Hyperventilation * 1    
# participants affected / at risk     0/9325 (0.00%)     1/9319 (0.01%)  
Nasal turbinate hypertrophy * 1    
# participants affected / at risk     1/9325 (0.01%)     0/9319 (0.00%)  
Pneumothorax * 1    
# participants affected / at risk     1/9325 (0.01%)     0/9319 (0.00%)  
Pulmonary mass * 1    
# participants affected / at risk     0/9325 (0.00%)     1/9319 (0.01%)  
Pulmonary thrombosis * 1    
# participants affected / at risk     1/9325 (0.01%)     0/9319 (0.00%)  
Rhinitis hypertrophic * 1    
# participants affected / at risk     0/9325 (0.00%)     1/9319 (0.01%)  
Sleep apnoea syndrome * 1    
# participants affected / at risk     1/9325 (0.01%)     0/9319 (0.00%)  
Status asthmaticus * 1    
# participants affected / at risk     0/9325 (0.00%)     1/9319 (0.01%)  
Skin and subcutaneous tissue disorders      
Urticaria * 1    
# participants affected / at risk     2/9325 (0.02%)     1/9319 (0.01%)  
Henoch-schonlein purpura * 1    
# participants affected / at risk     0/9325 (0.00%)     2/9319 (0.02%)  
Dermatitis atopic * 1    
# participants affected / at risk     1/9325 (0.01%)     0/9319 (0.00%)  
Erythema nodosum * 1    
# participants affected / at risk     0/9325 (0.00%)     1/9319 (0.01%)  
Psoriasis * 1    
# participants affected / at risk     1/9325 (0.01%)     0/9319 (0.00%)  
Pyoderma gangrenosum * 1    
# participants affected / at risk     0/9325 (0.00%)     1/9319 (0.01%)  
Renal colic * 1    
# participants affected / at risk     0/9325 (0.00%)     1/9319 (0.01%)  
Skin disorder * 1    
# participants affected / at risk     0/9325 (0.00%)     1/9319 (0.01%)  
Skin necrosis * 1    
# participants affected / at risk     1/9325 (0.01%)     0/9319 (0.00%)  
Stevens-johnson syndrome * 1    
# participants affected / at risk     0/9325 (0.00%)     1/9319 (0.01%)  
Urticaria chronic * 1    
# participants affected / at risk     0/9325 (0.00%)     1/9319 (0.01%)  
Social circumstances      
Homicide * 1    
# participants affected / at risk     2/9325 (0.02%)     1/9319 (0.01%)  
Surgical and medical procedures      
Abortion induced * 1    
# participants affected / at risk     3/9325 (0.03%)     5/9319 (0.05%)  
Breech extraction * 1    
# participants affected / at risk     1/9325 (0.01%)     0/9319 (0.00%)  
Nail operation * 1    
# participants affected / at risk     1/9325 (0.01%)     0/9319 (0.00%)  
Vascular disorders      
Deep vein thrombosis * 1    
# participants affected / at risk     3/9325 (0.03%)     2/9319 (0.02%)  
Circulatory collapse * 1    
# participants affected / at risk     0/9325 (0.00%)     1/9319 (0.01%)  
Haemorrhage * 1    
# participants affected / at risk     1/9325 (0.01%)     0/9319 (0.00%)  
Hypertension * 1    
# participants affected / at risk     1/9325 (0.01%)     0/9319 (0.00%)  
Hypertensive crisis * 1    
# participants affected / at risk     0/9325 (0.00%)     1/9319 (0.01%)  
Hypotension * 1    
# participants affected / at risk     1/9325 (0.01%)     0/9319 (0.00%)  
Jugular vein thrombosis * 1    
# participants affected / at risk     1/9325 (0.01%)     0/9319 (0.00%)  
Pelvic venous thrombosis * 1    
# participants affected / at risk     0/9325 (0.00%)     1/9319 (0.01%)  
Thrombosis * 1    
# participants affected / at risk     1/9325 (0.01%)     0/9319 (0.00%)  
Varicose vein * 1    
# participants affected / at risk     0/9325 (0.00%)     1/9319 (0.01%)  
Vasculitis * 1    
# participants affected / at risk     1/9325 (0.01%)     0/9319 (0.00%)  
Venous thrombosis * 1    
# participants affected / at risk     1/9325 (0.01%)     0/9319 (0.00%)  
* Events were collected by non-systematic assessment
1 Term from vocabulary, MedDRA 10.0




  Other Adverse Events


  Limitations and Caveats
  Hide Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.


  More Information