Clinical Trial Summary Template for Non-Interventional Studies

The study listed may include approved and non-approved uses, formulations or treatment regimens. The results reported in any single study may not reflect the overall results obtained on studies of a product. Before prescribing any product mentioned in this Register, healthcare professionals should consult prescribing information for the product approved in their country.

GSK Medicine: Contac Bien Z (Cetirizine HCl Tablet) Study Number: 200638 Title: Post Marketing Surveillance for Contac Bien Z in Japan. Rationale: This post-marketing surveillance (PMS) study was performed to collect and assess safety information on an over the counter (OTC) switched product as per the requirements of the Pharmaceutical and Medical Devices Agency (PMDA) in Japan. Study Period: 21 December 2012- 31 January 2016 (Surveillance Period) Objectives: The objective of the investigation was to collect and assess safety information on OTC cetirizine tablets by reviewing responses to the questionnaire provided by consumers who had purchased this product to relieve the symptoms of allergic rhinitis. Indication: Seasonal Allergic Rhinitis Study Investigator/Center: GSK CH Japan Research Method: Subjects (consumers), who had purchased OTC Contac Bien Z (Cetirizine Tablet) and agreed to participate in the study, received the questionnaire from a pharmacist. They completed the questionnaire after they used the product and then submitted the filled questionnaire to the pharmacist. Because it is an OTC drug, the observation period was not pre-fixed and allowed each respondent to decide. Data Source: Questionnaire (case report forms CRFs) Study Design: Post Marketing Surveillance (PMS) study Study Population: Subjects (consumers) who purchased OTC Contac Bien Z (Cetirizine Tablet) to relieve the symptoms associated with nasal allergy caused by pollen (sneezing, runny nose and nasal congestion) and agreed to take part in this PMS study. Study Outcomes: Primary: Safety outcome measure: incidence of adverse event (AEs) related to the drug (adverse drug reactions [ADRs]). Data Analysis Methods The AE incident rate was calculated based on the number of AEs against the total number of case reports collected through the questionnaires. Limitations: NA Study Results: During the surveillance period (21 December 2012- 31 January 2016) conducted with the questionnaires, 1,552 responses (cases) were collected from the 236 stores. According to the results, the number of adverse reaction cases (incidence rate) was 33 (2.13%) and the number of adverse reaction events was 51. Commonly reported symptoms of adverse reactions during the period of this post-marketing surveillance were 22 cases of nervous system disorders such as Somnolence, Headache and Dizziness and 12 cases of general disorders and administration site conditions including Thirst, Malaise and Feeling abnormal. None of these cases were considered serious as symptoms of adverse reactions. Demographics/Baseline Characteristics Total number of subjects (N) 1552 Age, years 15 - 90 Females: Males: Unknown, n (%) 911 (58.7%): 633 (40.8%): 8 (<1%)

Primary Outcome Table 1: Occurrence of Adverse Reactions by Category Surveillance before Cumulative total approval [1] after approval Facilities surveyed 923 stores 236 stores [2] Cases surveyed 7,155 cases 1,552 cases Adverse reaction cases 396 cases 33 cases

1 Adverse reaction occurrence 473 events 51 events Incidence of adverse reaction cases 5.53% 2.13% (3)÷2)×100) Distributed amount - 4,346,224 tablets

Number of adverse reactions Adverse reactions Surveillance before Cumulative total approval [1] after approval Infections and infestations 3 cases (0.04) - Furuncle 1 event (0.01) - Pharyngitis 2 events (0.03) - Sinusitis 1 event (0.01) - Immune system disorders 2 cases (0.03) - Hypersensitivity 1 event (0.01) - Allergic oedema 1 event (0.01) - Psychiatric disorders - 1 case (0.06) ＊Nightmare - 1 event (0.06) Metabolism and nutrition disorders 7 cases (0.10) - Decreased appetite 7 events (0.10) - Nervous system disorders 254 cases (3.55) 22 cases (1.42) Dizziness 9 events (0.13) 1 events (0.06) Dysgeusia 2 events (0.03) - Headache 12 events (0.17) 4 events (0.26)

Hypoaesthesia 5 events (0.07) - Sedation 1 event (0.01) - Somnolence 233 events (3.26) 22 events (1.42) Eye disorders 2 cases (0.03) 1 case (0.06) Vision blurred 1 event (0.01) - Conjunctival hyperaemia 1 event (0.01) - Eyelid oedema - 1 event (0.06) Ear and labyrinth disorders 2 cases (0.03) - Tinnitus 2 events (0.03) - Cardiac disorders 6 cases (0.08) - Arrhythmia 1 event (0.01) - Palpitations 4 events (0.06) - Tachycardia 1 event (0.01) - Vascular disorders 2 cases (0.03) - Hot flush 2 events (0.03) - Respiratory, thoracic and mediastinal 2 cases (0.03) 4 cases (0.26) disorders *Nasal dryness 1 event (0.01) - Respiratory distress 1 event (0.01) - Dry throat - 2 events (0.13) *Laryngeal discomfort - 1 event (0.06) Epistaxis - 1 event (0.06) Gastrointestinal disorders 49 cases (0.68) 2 cases (0.13) Abdominal discomfort 2 events (0.03) 2 events (0.13) Abdominal pain 3 events (0.04) - Abdominal pain upper 3 events (0.04) - Aphthous ulcer 1 event (0.01) - Cheilitis 1 event (0.01) - Constipation 2 events (0.03) - Diarrhoea 3 events (0.04) -

2 Dry mouth 2 events (0.03) - Dyspepsia 3 events (0.04) - Lip dry 2 events (0.03) 1 event (0.06) Nausea 10 events (0.14) - Abdominal discomfort 5 events (0.07) - Vomiting 1 event (0.01) - Buccal mucosal roughening 2 events (0.03) - Chapped lips 1 event (0.01) - Hypoaesthesia oral 1 event (0.01) - Abdominal symptom 1 event (0.01) - Hepatobiliary disorders 2 cases (0.03) - Hepatic function abnormal 2 events (0.03) - Skin and subcutaneous tissue 9 cases (0.13) 1 cases (0.06) disorders Dermatitis bullous 1 event (0.01) - Dermatitis contact 2 events (0.03) - Pruritus 2 events (0.03) - Rash 4 events (0.06) - Urticaria 1 event (0.01) - Eczema - 1 event (0.06) Musculoskeletal and connective 2 cases (0.03) 1 cases (0.06) tissue disorders Muscle spasms 1 event (0.01) Musculoskeletal stiffness 1 event (0.01) Myalgia 1 event (0.06) Renal and urinary disorders 2 cases (0.03) - Haematuria 1 event (0.01) - Pollakiuria 1 event (0.01) - Reproductive system and breast 2 cases (0.03) - disorders Menstruation irregular 2 events (0.03) - General disorders and administration 37 cases (0.52) 12 cases (0.77) site conditions Chest discomfort 1 event (0.01) - Chest pain 2 events (0.03) - Death 1 event (0.01) - Feeling abnormal 1 event (0.01) 3 events (0.19) Malaise 21 events (0.29) 4 events (0.26) Oedema 2 events (0.03) - Thirst 18 events (0.25) 6 events (0.39) Investigations 55 cases[3] - Alanine aminotransferase increased 19 events/6,940 cases - (0.27) Aspartate aminotransferase 18 events/6,941 cases - increased (0.25) Blood bilirubin increased 6 events/6,892 cases - (0.08) Blood pressure increased 1 event/7,155 cases - (0.01) Blood urea increased 4 events/6,931 cases - (0.06) Eosinophil count increased 9 events/6,873 cases - (0.13) Glucose urine present 2 events/6,822 cases - (0.03)

3 Lymphocyte count increased 2 events/6,876 cases - (0.03) Monocyte count increased 1 event/6,873 cases - (0.01) Neutrophil count decreased 3 events//6,873 cases - (0.04) White blood cell count decreased 2 events/6,934 cases - (0.03) Platelet count increased 1 event/6,907 cases - (0.01) Blood urine present 1 event/6,242 cases - (0.02) Protein urine present 4 events/6,822 cases - (0.06) Urobilinogen urine 1 event/6,816 cases - (0.01) Blood alkaline phosphatase 3 events/6,929 cases - increased (0.04) * Unexpected Adverse Reaction [1] It is the combined results from the clinical trials and the post marketing surveillance for the ethical drug of cetirizine hydrochloride. [2] Any duplicated facilities appearing in the first, second, third and fourth stages are aggregated. [3] No incident rate is generated due to different case number resulted from each clinical trial conducted before the approval performing different types of laboratory tests