A Study of Pembrolizumab (MK-3475) in Combination With Chemotherapy or Immunotherapy in Participants With Non-small Cell Lung Cancer (MK-3475-021/KEYNOTE-021)
Sponsor
Merck Sharp & Dohme LLC (Industry)
Overall Status
Completed
CT.gov ID
NCT02039674
Collaborator
(none)
267
14
91.9
Study Details
Study Description
Brief Summary
The purpose of this study is to determine the safety, tolerability, and efficacy of pembrolizumab (MK-3475) in combination with chemotherapy or immunotherapy in participants with unresectable or metastatic non-small cell lung cancer (NSCLC).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1/Phase 2 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
267 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase I/II Study of MK-3475 (SCH900475) in Combination With Chemotherapy or Immunotherapy in Patients With Locally Advanced or Metastatic Non-Small Cell Lung Carcinoma
Study Start Date
:
Feb 21, 2014
Actual Primary Completion Date
:
Nov 7, 2016
Actual Study Completion Date
:
Oct 18, 2021
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Part1 CohortA2 (Pembro2mg/kg+Paclitaxel [Pa]+Carboplatin [C]) Cohort A participants receive pembrolizumab (2 mg/kg) via intravenous (IV) infusion on Day 1 of each 3-week cycle PLUS paclitaxel (200 mg/m^2) via IV infusion on Day 1 of each 3-week cycle PLUS carboplatin (Aare Under the Curve [AUC] 6 [6 mg/mL/min]) via IV infusion on Day 1 of each 3-week cycle. |
Biological: Pembrolizumab
IV on Day 1 of each 3-week cycle prior to chemo/immunotherapy
Other Names:
Drug: Paclitaxel
IV on Day 1 of each 3-week cycle for a maximum of 4 administrations
Other Names:
Drug: Carboplatin
IV on Day 1 of each 3-week cycle for a maximum of 4 administrations
Other Names:
|
| Experimental: Part 1 Cohort B2 (Pembro 2mg/kg+Pa+C+Bevacizumab [B]) Cohort B2 participants receive pembrolizumab (2 mg/kg) via IV infusion on Day 1 of each 3-week cycle PLUS paclitaxel (200 mg/m^2) via IV infusion on Day 1 of each 3-week cycle PLUS carboplatin (AUC 6 [6 mg/mL/min]) via IV infusion on Day 1 of each 3-week cycle PLUS bevacizumab (15 mg/kg) via IV infusion on Day 1 of each 3-week cycle. |
Biological: Pembrolizumab
IV on Day 1 of each 3-week cycle prior to chemo/immunotherapy
Other Names:
Drug: Paclitaxel
IV on Day 1 of each 3-week cycle for a maximum of 4 administrations
Other Names:
Drug: Carboplatin
IV on Day 1 of each 3-week cycle for a maximum of 4 administrations
Other Names:
Biological: Bevacizumab
IV on Day 1 of each 3-week cycle
Other Names:
|
| Experimental: Part 1 Cohort C2 (Pembro 2mg/kg+Pemetrexed [Pe]+C) Cohort C2 participants receive pembrolizumab (2 mg/kg) via IV infusion on Day 1 of each 3-week cycle PLUS pemetrexed (500 mg/m^2) via IV infusion on Day 1 of each 3-week cycle PLUS carboplatin (AUC 5 [5 mg/mL/min]) via IV infusion on Day 1 of each 3-week cycle. |
Biological: Pembrolizumab
IV on Day 1 of each 3-week cycle prior to chemo/immunotherapy
Other Names:
Drug: Carboplatin
IV on Day 1 of each 3-week cycle for a maximum of 4 administrations
Other Names:
Drug: Pemetrexed
IV on Day 1 of each 3-week cycle
Other Names:
|
| Experimental: Part 1 Cohort D1 (Pembro 10mg/kg+Ipilimumab [I]) Cohort D1 participants receive pembrolizumab (10 mg/kg) via IV infusion on Day 1 of each 3-week cycle PLUS ipilimumab (1 mg/kg) via IV infusion on Day 1 of each 3-week cycle. |
Biological: Pembrolizumab
IV on Day 1 of each 3-week cycle prior to chemo/immunotherapy
Other Names:
Biological: Ipilimumab
IV on Day 1 of each 3-week cycle for a maximum of 4 administrations
Other Names:
|
| Experimental: Part 1 Cohort E (Pembro 2mg/kg+Erlotinib) Cohort E participants receive pembrolizumab (2 mg/kg) via IV infusion on Day 1 of each 3-week cycle PLUS erlotinib (150 mg) via oral tablet once a day on every day of each 3-week cycle. |
Biological: Pembrolizumab
IV on Day 1 of each 3-week cycle prior to chemo/immunotherapy
Other Names:
Drug: Erlotinib
Orally tablet once daily
Other Names:
|
| Experimental: Part 1 Cohort F (Pembro 2mg/kg+Gefitinib) Cohort F participants receive pembrolizumab (2 mg/kg) via IV infusion on Day 1 of each 3-week cycle PLUS gefitinib (250 mg) via oral tablet once a day on every day of each 3-week cycle. |
Biological: Pembrolizumab
IV on Day 1 of each 3-week cycle prior to chemo/immunotherapy
Other Names:
Drug: Gefitinib
Oral tablet once daily
Other Names:
|
| Experimental: Part 2 Cohort G+ (Pembro 200mg+C+Pe) Cohort G+ participants receive pembrolizumab (200 mg) via IV infusion on Day 1 of each 3-week cycle PLUS carboplatin (AUC 5 [5 mg/mL/min]) via IV infusion on Day 1 of each 3-week cycle PLUS pemetrexed (500 mg/m^2) via IV infusion on Day 1 of each 3-week cycle. |
Biological: Pembrolizumab
IV on Day 1 of each 3-week cycle prior to chemo/immunotherapy
Other Names:
Drug: Carboplatin
IV on Day 1 of each 3-week cycle for a maximum of 4 administrations
Other Names:
Drug: Pemetrexed
IV on Day 1 of each 3-week cycle
Other Names:
|
| Experimental: Part 2 Cohort H (Pembro+I) Cohort H participants receive pembrolizumab (2 mg/kg) via IV infusion on Day 1 of each 3-week cycle PLUS ipilimumab (1 mg/kg) via IV infusion on Day 1 of each 3-week cycle (at the recommended Phase II dose determined in Cohort D). |
Biological: Pembrolizumab
IV on Day 1 of each 3-week cycle prior to chemo/immunotherapy
Other Names:
Biological: Ipilimumab
IV on Day 1 of each 3-week cycle for a maximum of 4 administrations
Other Names:
|
| Experimental: Part 1 Cohort A10 (Pembro+Paclitaxel [Pa]+Carboplatin [C]) Cohort A10 participants receive pembrolizumab (10 mg/kg) via IV infusion on Day 1 of each 3-week cycle PLUS paclitaxel (200 mg/m^2) via IV infusion on Day 1 of each 3-week cycle PLUS carboplatin (AUC 6 [mg/mL/min]) via IV infusion on Day 1 of each 3-week cycle. |
Biological: Pembrolizumab
IV on Day 1 of each 3-week cycle prior to chemo/immunotherapy
Other Names:
Drug: Paclitaxel
IV on Day 1 of each 3-week cycle for a maximum of 4 administrations
Other Names:
Drug: Carboplatin
IV on Day 1 of each 3-week cycle for a maximum of 4 administrations
Other Names:
|
| Experimental: Part 1 Cohort B10 (Pembro+Pa+C+Bevacizumab [B]) Cohort B10 participants receive pembrolizumab (10 mg/kg) via IV infusion on Day 1 of each 3-week cycle PLUS paclitaxel (200 mg/m^2) via IV infusion on Day 1 of each 3-week cycle PLUS carboplatin (AUC 6 [6 mg/mL/min]) via IV infusion on Day 1 of each 3-week cycle PLUS bevacizumab (15 mg/kg) via IV infusion on Day 1 of each 3-week cycle. |
Biological: Pembrolizumab
IV on Day 1 of each 3-week cycle prior to chemo/immunotherapy
Other Names:
Drug: Paclitaxel
IV on Day 1 of each 3-week cycle for a maximum of 4 administrations
Other Names:
Drug: Carboplatin
IV on Day 1 of each 3-week cycle for a maximum of 4 administrations
Other Names:
Biological: Bevacizumab
IV on Day 1 of each 3-week cycle
Other Names:
|
| Experimental: Part 1 Cohort C10 (Pembro 10mg/kg+Pemetrexed [Pe]+C) Cohort C10 participants receive pembrolizumab (10 mg/kg) via IV infusion on Day 1 of each 3-week cycle PLUS pemetrexed (500 mg/m^2) via IV infusion on Day 1 of each 3-week cycle PLUS carboplatin (AUC 5 [5 mg/mL/min]) via IV infusion on Day 1 of each 3-week cycle. |
Biological: Pembrolizumab
IV on Day 1 of each 3-week cycle prior to chemo/immunotherapy
Other Names:
Drug: Carboplatin
IV on Day 1 of each 3-week cycle for a maximum of 4 administrations
Other Names:
Drug: Pemetrexed
IV on Day 1 of each 3-week cycle
Other Names:
|
| Experimental: Part 2 Cohort G- (Placebo+C+Pe) Cohort G- participants receive placebo (normal saline solution) via IV infusion on Day 1 of each 3-week cycle PLUS carboplatin (AUC 5 [5 mg/mL/min]) via IV infusion on Day 1 of each 3-week cycle PLUS pemetrexed (500 mg/m^2) via IV infusion on Day 1 of each 3-week cycle PLUS. |
Drug: Carboplatin
IV on Day 1 of each 3-week cycle for a maximum of 4 administrations
Other Names:
Drug: Pemetrexed
IV on Day 1 of each 3-week cycle
Other Names:
|
| Experimental: Part 1 Cohort D2 (Pembro 10mg/kg+Ipilimumab [I]) Cohort D2 participants receive pembrolizumab (10 mg/kg) via IV infusion on Day 1 of each 3-week cycle PLUS ipilimumab (3 mg/kg) via IV infusion on Day 1 of each 3-week cycle. |
Biological: Pembrolizumab
IV on Day 1 of each 3-week cycle prior to chemo/immunotherapy
Other Names:
Biological: Ipilimumab
IV on Day 1 of each 3-week cycle for a maximum of 4 administrations
Other Names:
|
| Experimental: Part 1 Cohort D4 (Pembro 2mg/kg+Ipilimumab [I]) Cohort D1 participants receive pembrolizumab (2 mg/kg) via IV infusion on Day 1 of each 3-week cycle PLUS ipilimumab (1 mg/kg) via IV infusion on Day 1 of each 3-week cycle. |
Biological: Pembrolizumab
IV on Day 1 of each 3-week cycle prior to chemo/immunotherapy
Other Names:
Biological: Ipilimumab
IV on Day 1 of each 3-week cycle for a maximum of 4 administrations
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Part 2 Cohorts G+ and G-: Objective Response Rate (ORR) [Up to approximately 2 years]
ORR was defined as the percentage of participants in the analysis population who had a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) per Response Criteria in Solid Tumors version 1.1 (RECIST 1.1) as assessed by blinded independent central review (BICR).
- Part 2 Cohorts D4 and H: Objective Response Rate (ORR) [Up to approximately 2 years]
For participants who demonstrated a confirmed response (Complete Response [CR]: Disappearance of all target lesions or Partial Response [PR]: At least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1. Per RECIST 1.1, DOR was defined as the time from first documented evidence of CR or PR until disease progression or death. DOR was assessed by BICR.
- All Cohorts: Number of Participants Who Experienced a Dose-limiting Toxicity (DLT) [Cycle 1 (Up to 21 days)]
DLTs were assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events version 4. A DLT was defined as any of the following events: Grade 4 non-hematologic toxicity (not laboratory); Grade 4 hematologic toxicity lasting ≥7 days; Grade 3 non-hematologic toxicity (not laboratory, specifically nausea, vomiting and diarrhea) lasting >3 days despite optimal supportive care; Any Grade 3 or Grade 4 non-hematologic laboratory value requiring treatment or hospitalization, or persisting for >1 week; Febrile neutropenia Grade 3 or Grade 4; Qualifying thrombocytopenia <25,000/mm^3; Prolonged delay (>2 weeks) in initiating Cycle 2 due to treatment-related toxicity; Missing >10% of erlotinib or gefitinib doses as a result of adverse events (AEs) during the DLT window of observation; or Grade 5 toxicity.
Secondary Outcome Measures
- Part 2 Cohorts G+ and G-: Progression-Free Survival (PFS) [Up to approximately 2 years]
PFS was defined as the time from randomization to the first documented disease progression, or death due to any cause, whichever occurred first. Per RECIST 1.1, progressive disease was defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions was also considered progression. PFS was assessed by BICR.
- Part 2 Cohorts G+ and G-: Overall Survival (OS) [Up to approximately 2 years]
OS was defined as the time from randomization to death due to any cause.
- Part 2 Cohorts G+ and G-: Duration of Response (DOR) [Up to approximately 2 years]
For participants who demonstrated a confirmed response (Complete Response [CR]: Disappearance of all target lesions or Partial Response [PR]: At least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1. Per RECIST 1.1, DOR was defined as the time from first documented evidence of CR or PR until disease progression or death. DOR was assessed by BICR.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Stage IIIb/IV NSCLC
-
Disease progression >1 year after completing adjuvant therapy for Stage I-IIIA disease and no systemic therapy for the recurrent disease
-
Resolution of any toxic effects (excepting alopecia) of the most recent therapy
-
At least one radiographically measurable lesion
-
Performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Status scale
-
Female participants of reproductive potential must not be pregnant (negative urine or serum human chorionic gonadotropin test within 72 hours of study start)
-
Female and male participants of reproductive potential must agree to use adequate contraception throughout the study period and for up to 120 days after the last dose of study therapy and for up to 180 days after the last dose of chemotherapeutic agents or tyrosine kinase inhibitors
Exclusion Criteria:
-
Currently participating or has participated in a study of an investigational agent or using an investigational device within 4 weeks of administration of pembrolizumab
-
Expected to require any other form of antineoplastic therapy while on study
-
Is on chronic systemic steroid therapy or on any other form of immunosuppressive medication
-
Has received a live-virus vaccination within 30 days of planned treatment start
-
Clinically active diverticulitis, intra-abdominal abscess, gastrointestinal (GI) obstruction, or abdominal carcinomatosis (known risks factors for bowel perforation)
-
History of a hematologic malignancy, primary brain tumor or sarcoma, or of another primary solid tumor, unless the participant has undergone potentially curative therapy with no evidence of that disease for 5 years
-
Active central nervous system (CNS) metastases and/or carcinomatous meningitis
-
Severe hypersensitivity reaction to treatment with another monoclonal antibody (mAb)
-
Active autoimmune disease that has required systemic treatment in the past 2 years (replacement therapies for hormone deficiencies are allowed)
-
Prior treatment with any other anti-programmed cell death protein-1 (anti-PD-1), or PD Ligand-1 (PD-L1) or PD Ligand-2 (PD-L2) agent or an antibody targeting other immuno-regulatory receptors or mechanisms
-
Systemic cytotoxic chemotherapy, antineoplastic biologic therapy, or major surgery within 3 weeks of the first dose of study medication
-
Radiation therapy to lung >30 Gy within 6 months of first dose of study medication
-
Prior tyrosine kinase inhibitor therapy or palliative radiation within 7 days of first dose of study medication
-
Active infection requiring therapy
-
History of Human Immunodeficiency Virus (HIV)
-
Active Hepatitis B or C
-
Symptomatic ascites or pleural effusion
-
Interstitial lung disease or pneumonitis requiring oral or IV glucocorticoids
-
Pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the study
-
Psychiatric disorders and substance (drug/alcohol) abuse
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Merck Sharp & Dohme LLC
Investigators
- Study Director: Medical Director, Merck Sharp & Dohme LLC
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.Responsible Party:
Merck Sharp & Dohme LLC
ClinicalTrials.gov Identifier:
NCT02039674
Other Study ID Numbers:
- 3475-021
- MK-3475-021
- KEYNOTE-021
First Posted:
Jan 17, 2014
Last Update Posted:
Nov 3, 2021
Last Verified:
Oct 1, 2021
Individual Participant Data (IPD) Sharing Statement:
Yes
Plan to Share IPD:
Yes
Keywords provided by Merck Sharp & Dohme LLC
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | This results disclosure is based on efficacy data cutoff dates of 08-Aug-2016 for Cohorts C & G, & 07-Nov-2016 for Cohorts A, B, D, E, F & H, & a safety data cutoff date of 07-Nov-2016. As of 07-Nov-2016, 96 participants were still ongoing in the study. |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Part1CohortA2 (Pembro 2 mg/kg+Paclitaxel [Pa]+Carboplatin [C]) | Part1CohortA10 (Pembro10mg/kg+Pa+C) | Part 1 Cohort B2 (Pembro 2mg/kg+Pa+C+Bevacizumab [B]) | Part 1 Cohort B10 (Pembro 10 mg/kg+Pa+C+B) | Part 1 Cohort C2 (Pembro 2 mg/kg+Pemetrexed [Pe]+C) | Part 1 Cohort C10 (Pembro 10 mg/kg+Pe+C) | Part 1 Cohort D1 (Pembro 10 mg/kg+Ipilimumab [I]) | Part 1 Cohort D2 (Pembro 10 mg/kg+I) | Part 1 Cohort D4 (Pembro 2 mg/kg+I) | Part 1 Cohort E (Pembro 2 mg/kg+Erlotinib) | Part 1 Cohort F (Pembro 2 mg/kg+Gefitinib) | Part 2 Cohort G+ (Pembro 200 mg+Pe+C) | Part 2 Cohort G- (Placebo+Pe+C) | Part 2 Cohort H (Pembro 2mg/kg+I) |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Cohort A2 participants received pembrolizumab (Pembro 2 mg/kg) via intravenous (IV) infusion on Day 1 of each 3-week cycle PLUS paclitaxel (Pa 200 mg/m^2) via IV infusion on Day 1 of each 3-week cycle PLUS carboplatin (C Area Under the Curve [AUC] 6 [6 mg/mL/min]) via IV infusion on Day 1 of each 3-week cycle. | Cohort A10 participants received pembrolizumab (Pembro 10 mg/kg) via IV infusion on Day 1 of each 3-week cycle PLUS paclitaxel (Pa 200 mg/m^2) via IV infusion on Day 1 of each 3-week cycle PLUS carboplatin (C AUC 6 [6 mg/mL/min]) via IV infusion on Day 1 of each 3-week cycle. | Cohort B2 participants received pembrolizumab (Pembro 2 mg/kg) via IV infusion on Day 1 of each 3-week cycle PLUS paclitaxel (Pa 200 mg/m^2) via IV infusion on Day 1 of each 3-week cycle PLUS carboplatin (C AUC 6 [6 mg/mL/min]) via IV infusion on Day 1 of each 3-week cycle PLUS bevacizumab (B 15 mg/kg) via IV infusion on Day 1 of each 3-week cycle. | Cohort B10 participants received pembrolizumab (Pembro 10 mg/kg) via IV infusion on Day 1 of each 3-week cycle PLUS paclitaxel (Pa 200 mg/m^2 via IV infusion on Day 1 of each 3-week cycle PLUS carboplatin (C AUC 6 [6 mg/mL/min]) via IV infusion on Day 1 of each 3-week cycle PLUS bevacizumab (B 15 mg/kg) via IV infusion on Day 1 of each 3-week cycle. | Cohort C2 participants received pembrolizumab (Pembro 2 mg/kg) via IV infusion on Day 1 of each 3-week cycle PLUS pemetrexed (Pe 500 mg/m^2) via IV infusion on Day 1 of each 3-week cycle PLUS carboplatin (C AUC 5 [5 mg/mL/min]) via IV infusion on Day 1 of each 3-week cycle. | Cohort C10 participants received pembrolizumab (Pembro 10 mg/kg) via IV infusion on Day 1 of each 3-week cycle PLUS pemetrexed (Pe 500 mg/m^2) via IV infusion on Day 1 of each 3-week cycle PLUS carboplatin (C AUC 6 [6 mg/mL/min]) via IV infusion on Day 1 of each 3-week cycle. | Cohort D1 participants received pembrolizumab (Pembro 10 mg/kg) via IV infusion on Day 1 of each 3-week cycle PLUS iIpilimumab (I 1 mg/kg) via IV infusion on Day 1 of each 3-week cycle. | Cohort D2 participants received pembrolizumab (Pembro 10 mg/kg) via IV infusion on Day 1 of each 3-week cycle PLUS iIpilimumab (I 3 mg/kg) via IV infusion on Day 1 of each 3-week cycle. | Cohort D4 participants received pembrolizumab (Pembro 2 mg/kg) via IV infusion on Day 1 of each 3-week cycle PLUS iIpilimumab (I 1 mg/kg) via IV infusion on Day 1 of each 3-week cycle. | Cohort E participants received pembrolizumab (Pembro 2 mg/kg) via IV infusion on Day 1 of each 3-week cycle PLUS erlotinib (E 150 mg) via oral tablet once a day on every day of each 3-week cycle. | Cohort F participants received pembrolizumab (Pembro 2 mg/kg) via IV infusion on Day 1 of each 3-week cycle PLUS gefitinib (G 250 mg) via oral tablet once a day on every day of each 3-week cycle. | Cohort G+ participants received pembrolizumab (Pembro 200 mg) via IV infusion on Day 1 of each 3-week cycle PLUS pemetrexed (Pe 500 mg/m^2) via IV infusion on Day 1 of each 3-week cycle PLUS carboplatin (C AUC 5 [5 mg/mL/min]) via IV infusion on Day 1 of each 3-week cycle. | Cohort G- participants received placebo (normal saline solution) via IV infusion on Day 1 of each 3-week cycle PLUS pemetrexed (Pe 500 mg/m^2) via IV infusion on Day 1 of each 3-week cycle PLUS carboplatin AUC 5 (C 5 mg/mL/min) via IV infusion on Day 1 of each 3-week cycle. | Cohort H participants received pembrolizumab (Pembro 2 mg/kg) via IV infusion on Day 1 of each 3-week cycle PLUS ipilimumab (I 1 mg/kg) via IV infusion on Day 1 of each 3-week cycle (at the recommended Phase 2 dose determined in Cohort D). |
| Period Title: Overall Study | ||||||||||||||
| STARTED | 13 | 12 | 12 | 13 | 12 | 12 | 3 | 3 | 12 | 12 | 7 | 60 | 63 | 33 |
| Treated | 13 | 12 | 11 | 13 | 12 | 12 | 3 | 3 | 12 | 12 | 7 | 59 | 62 | 33 |
| COMPLETED | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| NOT COMPLETED | 12 | 12 | 12 | 13 | 12 | 12 | 3 | 3 | 12 | 12 | 7 | 60 | 63 | 33 |
Baseline Characteristics
| Arm/Group Title | Part1CohortA2 (Pembro 2 mg/kg+Paclitaxel [Pa]+Carboplatin [C]) | Part1CohortA10 (Pembro10mg/kg+Pa+C) | Part 1 Cohort B2 (Pembro 2mg/kg+Pa+C+Bevacizumab [B]) | Part 1 Cohort B10 (Pembro 10 mg/kg+Pa+C+B) | Part 1 Cohort C2 (Pembro 2 mg/kg+Pemetrexed [Pe]+C) | Part 1 Cohort C10 (Pembro 10 mg/kg+Pe+C) | Part 1 Cohort D1 (Pembro 10 mg/kg+Ipilimumab [I]) | Part 1 Cohort D2 (Pembro 10 mg/kg+I) | Part 1 Cohort D4 (Pembro 2 mg/kg+I) | Part 1 Cohort E (Pembro 2 mg/kg+Erlotinib) | Part 1 Cohort F (Pembro 2 mg/kg+Gefitinib) | Part 2 Cohort G+ (Pembro 200 mg+Pe+C) | Part 2 Cohort G- (Placebo+Pe+C) | Part 2 Cohort H (Pembro 2 mg/kg+I) | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Cohort A2 participants received pembrolizumab (Pembro 2 mg/kg) via intravenous (IV) infusion on Day 1 of each 3-week cycle PLUS paclitaxel (Pa 200 mg/m^2) via IV infusion on Day 1 of each 3-week cycle PLUS carboplatin (C Area Under the Curve [AUC] 6 [6 mg/mL/min]) via IV infusion on Day 1 of each 3-week cycle. | Cohort A10 participants received pembrolizumab (Pembro 10 mg/kg) via IV infusion on Day 1 of each 3-week cycle PLUS paclitaxel (Pa 200 mg/m^2) via IV infusion on Day 1 of each 3-week cycle PLUS carboplatin (C AUC 6 [6 mg/mL/min]) via IV infusion on Day 1 of each 3-week cycle. | Cohort B2 participants received pembrolizumab (Pembro 2 mg/kg) via IV infusion on Day 1 of each 3-week cycle PLUS paclitaxel (Pa 200 mg/m^2) via IV infusion on Day 1 of each 3-week cycle PLUS carboplatin (C AUC 6 [6 mg/mL/min]) via IV infusion on Day 1 of each 3-week cycle PLUS bevacizumab (B 15 mg/kg) via IV infusion on Day 1 of each 3-week cycle. | Cohort B10 participants received pembrolizumab (Pembro 10 mg/kg) via IV infusion on Day 1 of each 3-week cycle PLUS paclitaxel (Pa 200 mg/m^2 via IV infusion on Day 1 of each 3-week cycle PLUS carboplatin (C AUC 6 [6 mg/mL/min]) via IV infusion on Day 1 of each 3-week cycle PLUS bevacizumab (B 15 mg/kg) via IV infusion on Day 1 of each 3-week cycle. | Cohort C2 participants received pembrolizumab (Pembro 2 mg/kg) via IV infusion on Day 1 of each 3-week cycle PLUS pemetrexed (Pe 500 mg/m^2) via IV infusion on Day 1 of each 3-week cycle PLUS carboplatin (C AUC 5 [5 mg/mL/min]) via IV infusion on Day 1 of each 3-week cycle. | Cohort C10 participants received pembrolizumab (Pembro 10 mg/kg) via IV infusion on Day 1 of each 3-week cycle PLUS pemetrexed (Pe 500 mg/m^2) via IV infusion on Day 1 of each 3-week cycle PLUS carboplatin (C AUC 6 [6 mg/mL/min]) via IV infusion on Day 1 of each 3-week cycle. | Cohort D1 participants received pembrolizumab (Pembro 10 mg/kg) via IV infusion on Day 1 of each 3-week cycle PLUS ipilimumab (I 1 mg/kg) via IV infusion on Day 1 of each 3-week cycle. | Cohort D2 participants received pembrolizumab (Pembro 10 mg/kg) via IV infusion on Day 1 of each 3-week cycle PLUS ipilimumab (I 3 mg/kg) via IV infusion on Day 1 of each 3-week cycle. | Cohort D4 participants received pembrolizumab (Pembro 2 mg/kg) via IV infusion on Day 1 of each 3-week cycle PLUS ipilimumab (I 1 mg/kg) via IV infusion on Day 1 of each 3-week cycle. | Cohort E participants received pembrolizumab (Pembro 2 mg/kg) via IV infusion on Day 1 of each 3-week cycle PLUS erlotinib (E 150 mg) via oral tablet once a day on every day of each 3-week cycle. | Cohort F participants received pembrolizumab (Pembro 2 mg/kg) via IV infusion on Day 1 of each 3-week cycle PLUS gefitinib (G 250 mg) via oral tablet once a day on every day of each 3-week cycle. | Cohort G+ participants received pembrolizumab (Pembro 200 mg) via IV infusion on Day 1 of each 3-week cycle PLUS carboplatin (C AUC 5 [5 mg/mL/min]) via IV infusion on Day 1 of each 3-week cycle PLUS pemetrexed (Pe 500 mg/m^2) via IV infusion on Day 1 of each 3-week cycle. | Cohort G- participants received placebo (normal saline solution) via IV infusion on Day 1 of each 3-week cycle PLUS pemetrexed (Pe 500 mg/m^2) via IV infusion on Day 1 of each 3-week cycle PLUS carboplatin (C AUC 5 [5 mg/mL/min]) via IV infusion on Day 1 of each 3-week cycle. | Cohort H participants received pembrolizumab (Pembro 2 mg/kg) via IV infusion on Day 1 of each 3-week cycle PLUS ipilimumab (I 1 mg/kg) via IV infusion on Day 1 of each 3-week cycle (at the recommended Phase 2 dose determined in Cohort D). | Total of all reporting groups |
| Overall Participants | 13 | 12 | 12 | 13 | 12 | 12 | 3 | 3 | 12 | 12 | 7 | 60 | 63 | 33 | 267 |
| Age (Years) [Mean (Standard Deviation) ] | |||||||||||||||
| Mean (Standard Deviation) [Years] |
64.5
(8.0)
|
61.4
(9.2)
|
61.2
(5.1)
|
59.5
(9.1)
|
60.3
(11.0)
|
63.3
(8.4)
|
69.3
(6.0)
|
59.3
(5.5)
|
55.3
(14.0)
|
60.2
(8.0)
|
62.7
(12.0)
|
61.8
(9.2)
|
63.2
(9.6)
|
62.2
(9.7)
|
61.8
(9.5)
|
| Sex: Female, Male (Count of Participants) | |||||||||||||||
| Female |
5
38.5%
|
8
66.7%
|
6
50%
|
6
46.2%
|
6
50%
|
6
50%
|
2
66.7%
|
1
33.3%
|
4
33.3%
|
6
50%
|
4
57.1%
|
38
63.3%
|
37
58.7%
|
18
54.5%
|
147
55.1%
|
| Male |
8
61.5%
|
4
33.3%
|
6
50%
|
7
53.8%
|
6
50%
|
6
50%
|
1
33.3%
|
2
66.7%
|
8
66.7%
|
6
50%
|
3
42.9%
|
22
36.7%
|
26
41.3%
|
15
45.5%
|
120
44.9%
|
Outcome Measures
| Title | Part 2 Cohorts G+ and G-: Objective Response Rate (ORR) |
|---|---|
| Description | ORR was defined as the percentage of participants in the analysis population who had a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) per Response Criteria in Solid Tumors version 1.1 (RECIST 1.1) as assessed by blinded independent central review (BICR). |
| Time Frame | Up to approximately 2 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population consisted of all randomized Cohort G participants. |
| Arm/Group Title | Part 2 Cohort G+ (Pembro 200 mg+Pe+C) | Part 2 Cohort G- (Placebo+Pe+C) |
|---|---|---|
| Arm/Group Description | Cohort G+ participants received pembrolizumab (Pembro 200 mg) via IV infusion on Day 1 of each 3-week cycle PLUS carboplatin (C AUC 5 [5 mg/mL/min]) via IV infusion on Day 1 of each 3-week cycle PLUS pemetrexed (Pe 500 mg/m^2) via IV infusion on Day 1 of each 3-week cycle. | Cohort G- participants received placebo (normal saline solution) via IV infusion on Day 1 of each 3-week cycle PLUS pemetrexed (Pe 500 mg/m^2) via IV infusion on Day 1 of each 3-week cycle PLUS carboplatin (C AUC 5 [5 mg/mL/min]) via IV infusion on Day 1 of each 3-week cycle. |
| Measure Participants | 60 | 63 |
| Number (95% Confidence Interval) [Percentage of Participants] |
55.0
423.1%
|
28.6
238.3%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Part 2 Cohort G+ (Pembro 200 mg+Pe+C), Part 2 Cohort G- (Placebo+Pe+C) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0016 |
| Comments | ||
| Method | Miettinen & Nurminen Method | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in Percentages |
| Estimated Value | 26.3 | |
| Confidence Interval |
(2-Sided) 95% 8.9 to 42.1 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Part 2 Cohorts D4 and H: Objective Response Rate (ORR) |
|---|---|
| Description | For participants who demonstrated a confirmed response (Complete Response [CR]: Disappearance of all target lesions or Partial Response [PR]: At least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1. Per RECIST 1.1, DOR was defined as the time from first documented evidence of CR or PR until disease progression or death. DOR was assessed by BICR. |
| Time Frame | Up to approximately 2 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population consisted of all treated Cohort D4 and Cohort H participants. One Cohort H participant was excluded from the efficacy analysis population due to a protocol violation. This participant did not have non-small cell lung cancer. |
| Arm/Group Title | Part 2 Cohorts D4 & H (Pembro 2mg/kg+I) |
|---|---|
| Arm/Group Description | Cohort D4 and Cohort H participants received pembrolizumab (Pembro 2 mg/kg) via IV infusion on Day 1 of each 3-week cycle PLUS ipilimumab (I 1 mg/kg) via IV infusion on Day 1 of each 3-week cycle (at the recommended Phase 2 dose determined in Cohort D). |
| Measure Participants | 44 |
| Number (95% Confidence Interval) [Percentage of Participants] |
29.5
226.9%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Part 2 Cohort G+ (Pembro 200 mg+Pe+C) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0858 |
| Comments | ||
| Method | Exact binomial distribution for testing | |
| Comments | HO: ORR ≤20% versus H1: ORR >20% | |
| Title | All Cohorts: Number of Participants Who Experienced a Dose-limiting Toxicity (DLT) |
|---|---|
| Description | DLTs were assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events version 4. A DLT was defined as any of the following events: Grade 4 non-hematologic toxicity (not laboratory); Grade 4 hematologic toxicity lasting ≥7 days; Grade 3 non-hematologic toxicity (not laboratory, specifically nausea, vomiting and diarrhea) lasting >3 days despite optimal supportive care; Any Grade 3 or Grade 4 non-hematologic laboratory value requiring treatment or hospitalization, or persisting for >1 week; Febrile neutropenia Grade 3 or Grade 4; Qualifying thrombocytopenia <25,000/mm^3; Prolonged delay (>2 weeks) in initiating Cycle 2 due to treatment-related toxicity; Missing >10% of erlotinib or gefitinib doses as a result of adverse events (AEs) during the DLT window of observation; or Grade 5 toxicity. |
| Time Frame | Cycle 1 (Up to 21 days) |
Outcome Measure Data
| Analysis Population Description |
|---|
| The DLT evaluable population consisted of all participants who completed the first cycle of study treatment or who discontinued from the study due to a drug-related AE. |
| Arm/Group Title | Part1CohortA2 (Pembro 2 mg/kg+Paclitaxel [Pa]+Carboplatin [C]) | Part1CohortA10 (Pembro10mg/kg+Pa+C) | Part 1 Cohort B2 (Pembro 2mg/kg+Pa+C+Bevacizumab [B]) | Part 1 Cohort B10 (Pembro 10 mg/kg+Pa+C+B) | Part 1 Cohort C2 (Pembro 2 mg/kg+Pemetrexed [Pe]+C) | Part 1 Cohort C10 (Pembro 10 mg/kg+Pe+C) | Part 1 Cohort D1 (Pembro 10mg/kg+Ipilimumab [I]) | Part 1 Cohort D2 (Pembro 10 mg/kg+I) | Part 1 Cohort D4 (Pembro 2 mg/kg+I) | Part 1 Cohort E (Pembro 2 mg/kg+Erlotinib) | Part 1 Cohort F (Pembro 2 mg/kg+Gefitinib) | Part 2 Cohort G+ (Pembro 200 mg+Pe+C) | Part 2 Cohort G- (Placebo+Pe+C) | Part 2 Cohort H (Pembro 2 mg/kg+I) |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Cohort A2 participants received pembrolizumab (Pembro 2 mg/kg) via intravenous (IV) infusion on Day 1 of each 3-week cycle PLUS paclitaxel (Pa 200 mg/m^2) via IV infusion on Day 1 of each 3-week cycle PLUS carboplatin (C Area Under the Curve [AUC] 6 [6 mg/mL/min]) via IV infusion on Day 1 of each 3-week cycle. | Cohort A10 participants received pembrolizumab (Pembro 10 mg/kg) via IV infusion on Day 1 of each 3-week cycle PLUS paclitaxel (Pa 200 mg/m^2) via IV infusion on Day 1 of each 3-week cycle PLUS carboplatin (C AUC 6 [6 mg/mL/min]) via IV infusion on Day 1 of each 3-week cycle. | Cohort B2 participants received pembrolizumab (Pembro 2 mg/kg) via IV infusion on Day 1 of each 3-week cycle PLUS paclitaxel (Pa 200 mg/m^2) via IV infusion on Day 1 of each 3-week cycle PLUS carboplatin (C AUC 6 [6 mg/mL/min]) via IV infusion on Day 1 of each 3-week cycle PLUS bevacizumab (B 15 mg/kg) via IV infusion on Day 1 of each 3-week cycle. | Cohort B10 participants received pembrolizumab (Pembro 10 mg/kg) via IV infusion on Day 1 of each 3-week cycle PLUS paclitaxel (Pa 200 mg/m^2 via IV infusion on Day 1 of each 3-week cycle PLUS carboplatin (C AUC 6 [6 mg/mL/min]) via IV infusion on Day 1 of each 3-week cycle PLUS bevacizumab (B 15 mg/kg) via IV infusion on Day 1 of each 3-week cycle. | Cohort C2 participants received pembrolizumab (Pembro 2 mg/kg) via IV infusion on Day 1 of each 3-week cycle PLUS pemetrexed (Pe 500 mg/m^2) via IV infusion on Day 1 of each 3-week cycle PLUS carboplatin (C AUC 5 [5 mg/mL/min]) via IV infusion on Day 1 of each 3-week cycle. | Cohort C10 participants received pembrolizumab (Pembro 10 mg/kg) via IV infusion on Day 1 of each 3-week cycle PLUS pemetrexed (Pe 500 mg/m^2) via IV infusion on Day 1 of each 3-week cycle PLUS carboplatin (C AUC 6 [6 mg/mL/min]) via IV infusion on Day 1 of each 3-week cycle. | Cohort D1 participants received pembrolizumab (Pembro 10 mg/kg) via IV infusion on Day 1 of each 3-week cycle PLUS iIpilimumab (I 1 mg/kg) via IV infusion on Day 1 of each 3-week cycle. | Cohort D2 participants received pembrolizumab (Pembro 10 mg/kg) via IV infusion on Day 1 of each 3-week cycle PLUS ipilimumab (I 3 mg/kg) via IV infusion on Day 1 of each 3-week cycle. | Cohort D4 participants received pembrolizumab (Pembro 2 mg/kg) via IV infusion on Day 1 of each 3-week cycle PLUS ipilimumab (I 1 mg/kg) via IV infusion on Day 1 of each 3-week cycle. | Cohort E participants received pembrolizumab (Pembro 2 mg/kg) via IV infusion on Day 1 of each 3-week cycle PLUS erlotinib (E 150 mg) via oral tablet once a day on every day of each 3-week cycle. | Cohort F participants received pembrolizumab (Pembro 2 mg/kg) via IV infusion on Day 1 of each 3-week cycle PLUS gefitinib (G 250 mg) via oral tablet once a day on every day of each 3-week cycle. | Cohort G+ participants received pembrolizumab (Pembro 200 mg) via IV infusion on Day 1 of each 3-week cycle PLUS carboplatin (C AUC 5 [5 mg/mL/min]) via IV infusion on Day 1 of each 3-week cycle PLUS pemetrexed (Pe 500 mg/m^2) via IV infusion on Day 1 of each 3-week cycle. | Cohort G- participants received placebo (normal saline solution) via IV infusion on Day 1 of each 3-week cycle PLUS pemetrexed (Pe 500 mg/m^2) via IV infusion on Day 1 of each 3-week cycle PLUS carboplatin (C AUC 5 [5 mg/mL/min]) via IV infusion on Day 1 of each 3-week cycle. | Cohort H participants received pembrolizumab (Pembro 2 mg/kg) via IV infusion on Day 1 of each 3-week cycle PLUS ipilimumab (I 1 mg/kg) via IV infusion on Day 1 of each 3-week cycle (at the recommended Phase 2 dose determined in Cohort D). |
| Measure Participants | 13 | 12 | 11 | 13 | 12 | 12 | 3 | 3 | 12 | 12 | 7 | 59 | 62 | 33 |
| Count of Participants [Participants] |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Title | Part 2 Cohorts G+ and G-: Progression-Free Survival (PFS) |
|---|---|
| Description | PFS was defined as the time from randomization to the first documented disease progression, or death due to any cause, whichever occurred first. Per RECIST 1.1, progressive disease was defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions was also considered progression. PFS was assessed by BICR. |
| Time Frame | Up to approximately 2 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population consisted of all randomized Cohort G participants. |
| Arm/Group Title | Part 2 Cohort G+ (Pembro 200 mg+Pe+C) | Part 2 Cohort G- (Placebo+Pe+C) |
|---|---|---|
| Arm/Group Description | Cohort G+ participants received pembrolizumab (Pembro 200 mg) via IV infusion on Day 1 of each 3-week cycle PLUS carboplatin (C AUC 5 [5 mg/mL/min]) via IV infusion on Day 1 of each 3-week cycle PLUS pemetrexed (Pe 500 mg/m^2) via IV infusion on Day 1 of each 3-week cycle. | Cohort G- participants received placebo (normal saline solution) via IV infusion on Day 1 of each 3-week cycle PLUS pemetrexed (Pe 500 mg/m^2) via IV infusion on Day 1 of each 3-week cycle PLUS carboplatin (C AUC 5 [5 mg/mL/min]) via IV infusion on Day 1 of each 3-week cycle. |
| Measure Participants | 60 | 63 |
| Median (95% Confidence Interval) [Months] |
13.0
|
8.9
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Part 2 Cohort G+ (Pembro 200 mg+Pe+C), Part 2 Cohort G- (Placebo+Pe+C) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.01024 |
| Comments | ||
| Method | Log Rank | |
| Comments | One-sided p-value based on log-rank test | |
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.53 | |
| Confidence Interval |
(2-Sided) 95% 0.31 to 0.91 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Part 2 Cohorts G+ and G-: Overall Survival (OS) |
|---|---|
| Description | OS was defined as the time from randomization to death due to any cause. |
| Time Frame | Up to approximately 2 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population consisted of all randomized Cohort G participants. |
| Arm/Group Title | Part 2 Cohort G+ (Pembro 200 mg+Pe+C) | Part 2 Cohort G- (Placebo+Pe+C) |
|---|---|---|
| Arm/Group Description | Cohort G+ participants received pembrolizumab (Pembro 200 mg) via IV infusion on Day 1 of each 3-week cycle PLUS carboplatin (C AUC 5 [5 mg/mL/min]) via IV infusion on Day 1 of each 3-week cycle PLUS pemetrexed (Pe 500 mg/m^2) via IV infusion on Day 1 of each 3-week cycle. | Cohort G- participants received placebo (normal saline solution) via IV infusion on Day 1 of each 3-week cycle PLUS pemetrexed (Pe 500 mg/m^2) via IV infusion on Day 1 of each 3-week cycle PLUS carboplatin (C AUC 5 [5 mg/mL/min]) via IV infusion on Day 1 of each 3-week cycle. |
| Measure Participants | 60 | 63 |
| Median (95% Confidence Interval) [Months] |
NA
|
NA
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Part 2 Cohort G+ (Pembro 200 mg+Pe+C), Part 2 Cohort G- (Placebo+Pe+C) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.38912 |
| Comments | ||
| Method | Log Rank | |
| Comments | One-sided p-value based on log-rank test | |
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.90 | |
| Confidence Interval |
(2-Sided) 95% 0.42 to 1.91 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Part 2 Cohorts G+ and G-: Duration of Response (DOR) |
|---|---|
| Description | For participants who demonstrated a confirmed response (Complete Response [CR]: Disappearance of all target lesions or Partial Response [PR]: At least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1. Per RECIST 1.1, DOR was defined as the time from first documented evidence of CR or PR until disease progression or death. DOR was assessed by BICR. |
| Time Frame | Up to approximately 2 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population consisted of all randomized Cohort G participants who experienced a confirmed response (CR or PR). |
| Arm/Group Title | Part 2 Cohort G+ (Pembro 200 mg+Pe+C) | Part 2 Cohort G- (Placebo+Pe+C) |
|---|---|---|
| Arm/Group Description | Cohort G+ participants received pembrolizumab (Pembro 200 mg) via IV infusion on Day 1 of each 3-week cycle PLUS carboplatin (C AUC 5 [5 mg/mL/min]) via IV infusion on Day 1 of each 3-week cycle PLUS pemetrexed (Pe 500 mg/m^2) via IV infusion on Day 1 of each 3-week cycle. | Cohort G- participants received placebo (normal saline solution) via IV infusion on Day 1 of each 3-week cycle PLUS pemetrexed (Pe 500 mg/m^2) via IV infusion on Day 1 of each 3-week cycle PLUS carboplatin (C AUC 5 [5 mg/mL/min]) via IV infusion on Day 1 of each 3-week cycle. |
| Measure Participants | 33 | 18 |
| Median (Full Range) [Months] |
NA
|
NA
|
Adverse Events
| Time Frame | Serious AEs: Up to 90 days after last dose of study treatment (Up to 27 months) Non-serious AEs: Up to 30 days after last dose of study treatment (Up to 25 months) | |||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | Safety Population: All treated participants. All-Cause Mortality Population: All randomized participants. Per protocol, disease progression of cancer under study was not considered an adverse event (AE) unless considered related to study treatment. Thus, Medical Dictionary for Regulatory Activities (MedDRA) preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study treatment are excluded as AEs. | |||||||||||||||||||||||||||
| Arm/Group Title | Part1CohortA2 (Pembro 2mg/kg+Paclitaxel [Pa]+Carboplatin [C]) | Part1 CohortA10 (Pembro10mg/kg+Pa+C) | Part 1 Cohort B2 (Pembro 2mg/kg+Pa+C+Bevacizumab [B]) | Part 1 Cohort B10 (Pembro 10 mg/kg+Pa+C+B) | Part 1 Cohort C2 (Pembro 2 mg/kg+Pemetrexed [Pe]+C) | Part 1 Cohort C10 (Pembro 10 mg/kg+Pe+C) | Part 1 Cohort D1 (Pembro 10 mg/kg+Ipilimumab [I]) | Part 1 Cohort D2 (Pembro 10 mg/kg+I) | Part 1 Cohort D4 (Pembro 2 mg/kg+I) | Part 1 Cohort E (Pembro 2 mg/kg+Erlotinib) | Part 1 Cohort F (Pembro 2 mg/kg+Gefitinib) | Part 2 Cohort G+ (Pembro 200 mg+Pe+C) | Part 2 Cohort G- (Placebo+Pe+C) | Part 2 Cohort H (Pembro 2mg/kg+I) | ||||||||||||||
| Arm/Group Description | Cohort A2 participants received pembrolizumab (Pembro 2 mg/kg) via IV infusion on Day 1 of each 3-week cycle PLUS paclitaxel (Pa 200 mg/m^2) via IV infusion on Day 1 of each 3-week cycle PLUS carboplatin (C AUC 6 [6 mg/mL/min]) via IV infusion on Day 1 of each 3-week cycle. | Cohort A10 participants received pembrolizumab (Pembro 10 mg/kg) via IV infusion on Day 1 of each 3-week cycle PLUS paclitaxel (Pa 200 mg/m^2) via IV infusion on Day 1 of each 3-week cycle PLUS carboplatin (C AUC 6 [6 mg/mL/min]) via IV infusion on Day 1 of each 3-week cycle. | Cohort B2 participants received pembrolizumab (Pembro 2 mg/kg) via IV infusion on Day 1 of each 3-week cycle PLUS paclitaxel (Pa 200 mg/m^2) via IV infusion on Day 1 of each 3-week cycle PLUS carboplatin (C AUC 6 [6 mg/mL/min]) via IV infusion on Day 1 of each 3-week cycle PLUS bevacizumab (B 15 mg/kg) via IV infusion on Day 1 of each 3-week cycle. | Cohort B10 participants received pembrolizumab (Pembro 10 mg/kg) via IV infusion on Day 1 of each 3-week cycle PLUS paclitaxel (Pa 200 mg/m^2 via IV infusion on Day 1 of each 3-week cycle PLUS carboplatin (C AUC 6 [6 mg/mL/min]) via IV infusion on Day 1 of each 3-week cycle PLUS bevacizumab (B 15 mg/kg) via IV infusion on Day 1 of each 3-week cycle. | Cohort C2 participants received pembrolizumab (Pembro 2 mg/kg) via IV infusion on Day 1 of each 3-week cycle PLUS pemetrexed (Pe 500 mg/m^2) via IV infusion on Day 1 of each 3-week cycle PLUS carboplatin (C AUC 5 [5 mg/mL/min]) via IV infusion on Day 1 of each 3-week cycle. | Cohort C10 participants received pembrolizumab (Pembro 10 mg/kg) via IV infusion on Day 1 of each 3-week cycle PLUS pemetrexed (Pe 500 mg/m^2) via IV infusion on Day 1 of each 3-week cycle PLUS carboplatin (C AUC 6 [6 mg/mL/min]) via IV infusion on Day 1 of each 3-week cycle. | Cohort D1 participants received pembrolizumab (Pembro 10 mg/kg) via IV infusion on Day 1 of each 3-week cycle PLUS ipilimumab (I 1 mg/kg) via IV infusion on Day 1 of each 3-week cycle. | Cohort D2 participants received pembrolizumab (Pembro 10 mg/kg) via IV infusion on Day 1 of each 3-week cycle PLUS ipilimumab (I 3 mg/kg) via IV infusion on Day 1 of each 3-week cycle. | Cohort D4 participants received pembrolizumab (Pembro 2 mg/kg) via IV infusion on Day 1 of each 3-week cycle PLUS ipilimumab (I 1 mg/kg) via IV infusion on Day 1 of each 3-week cycle. | Cohort E participants received pembrolizumab (Pembro 2 mg/kg) via IV infusion on Day 1 of each 3-week cycle PLUS erlotinib (E 150 mg) via oral tablet once a day on every day of each 3-week cycle. | Cohort F participants received pembrolizumab (Pembro 2 mg/kg) via IV infusion on Day 1 of each 3-week cycle PLUS gefitinib (G 250 mg) via oral tablet once a day on every day of each 3-week cycle. | Cohort G+ participants received pembrolizumab (Pembro 200 mg) via IV infusion on Day 1 of each 3-week cycle PLUS carboplatin (C AUC 5 [5 mg/mL/min]) via IV infusion on Day 1 of each 3-week cycle PLUS pemetrexed (Pe 500 mg/m^2) via IV infusion on Day 1 of each 3-week cycle. | Cohort G- participants received placebo (normal saline solution) via IV infusion on Day 1 of each 3-week cycle PLUS pemetrexed (Pe 500 mg/m^2) via IV infusion on Day 1 of each 3-week cycle PLUS carboplatin (C AUC 5 [5 mg/mL/min]) via IV infusion on Day 1 of each 3-week cycle. | Cohort H participants received pembrolizumab (Pembro 2 mg/kg) via IV infusion on Day 1 of each 3-week cycle PLUS ipilimumab (I 1 mg/kg) via IV infusion on Day 1 of each 3-week cycle (at the recommended Phase 2 dose determined in Cohort D). | ||||||||||||||
All Cause Mortality |
||||||||||||||||||||||||||||
| Part1CohortA2 (Pembro 2mg/kg+Paclitaxel [Pa]+Carboplatin [C]) | Part1 CohortA10 (Pembro10mg/kg+Pa+C) | Part 1 Cohort B2 (Pembro 2mg/kg+Pa+C+Bevacizumab [B]) | Part 1 Cohort B10 (Pembro 10 mg/kg+Pa+C+B) | Part 1 Cohort C2 (Pembro 2 mg/kg+Pemetrexed [Pe]+C) | Part 1 Cohort C10 (Pembro 10 mg/kg+Pe+C) | Part 1 Cohort D1 (Pembro 10 mg/kg+Ipilimumab [I]) | Part 1 Cohort D2 (Pembro 10 mg/kg+I) | Part 1 Cohort D4 (Pembro 2 mg/kg+I) | Part 1 Cohort E (Pembro 2 mg/kg+Erlotinib) | Part 1 Cohort F (Pembro 2 mg/kg+Gefitinib) | Part 2 Cohort G+ (Pembro 200 mg+Pe+C) | Part 2 Cohort G- (Placebo+Pe+C) | Part 2 Cohort H (Pembro 2mg/kg+I) | |||||||||||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/13 (0%) | 0/12 (0%) | 1/12 (8.3%) | 2/13 (15.4%) | 0/12 (0%) | 2/12 (16.7%) | 0/3 (0%) | 0/3 (0%) | 0/12 (0%) | 0/12 (0%) | 1/7 (14.3%) | 1/60 (1.7%) | 0/63 (0%) | 8/33 (24.2%) | ||||||||||||||
Serious Adverse Events |
||||||||||||||||||||||||||||
| Part1CohortA2 (Pembro 2mg/kg+Paclitaxel [Pa]+Carboplatin [C]) | Part1 CohortA10 (Pembro10mg/kg+Pa+C) | Part 1 Cohort B2 (Pembro 2mg/kg+Pa+C+Bevacizumab [B]) | Part 1 Cohort B10 (Pembro 10 mg/kg+Pa+C+B) | Part 1 Cohort C2 (Pembro 2 mg/kg+Pemetrexed [Pe]+C) | Part 1 Cohort C10 (Pembro 10 mg/kg+Pe+C) | Part 1 Cohort D1 (Pembro 10 mg/kg+Ipilimumab [I]) | Part 1 Cohort D2 (Pembro 10 mg/kg+I) | Part 1 Cohort D4 (Pembro 2 mg/kg+I) | Part 1 Cohort E (Pembro 2 mg/kg+Erlotinib) | Part 1 Cohort F (Pembro 2 mg/kg+Gefitinib) | Part 2 Cohort G+ (Pembro 200 mg+Pe+C) | Part 2 Cohort G- (Placebo+Pe+C) | Part 2 Cohort H (Pembro 2mg/kg+I) | |||||||||||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 7/13 (53.8%) | 5/12 (41.7%) | 8/11 (72.7%) | 8/13 (61.5%) | 6/12 (50%) | 7/12 (58.3%) | 2/3 (66.7%) | 1/3 (33.3%) | 5/12 (41.7%) | 6/12 (50%) | 5/7 (71.4%) | 27/59 (45.8%) | 18/62 (29%) | 11/33 (33.3%) | ||||||||||||||
| Blood and lymphatic system disorders | ||||||||||||||||||||||||||||
| Anaemia | 0/13 (0%) | 0 | 1/12 (8.3%) | 1 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 2/12 (16.7%) | 2 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 1/59 (1.7%) | 1 | 2/62 (3.2%) | 2 | 0/33 (0%) | 0 |
| Febrile neutropenia | 2/13 (15.4%) | 3 | 0/12 (0%) | 0 | 2/11 (18.2%) | 2 | 1/13 (7.7%) | 1 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 1/59 (1.7%) | 1 | 1/62 (1.6%) | 1 | 0/33 (0%) | 0 |
| Neutropenia | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 1/13 (7.7%) | 1 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 1/62 (1.6%) | 1 | 0/33 (0%) | 0 |
| Pancytopenia | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 1/59 (1.7%) | 1 | 2/62 (3.2%) | 2 | 1/33 (3%) | 1 |
| Thrombocytopenia | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 1/59 (1.7%) | 1 | 1/62 (1.6%) | 1 | 0/33 (0%) | 0 |
| Cardiac disorders | ||||||||||||||||||||||||||||
| Aortic valve disease | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 1/12 (8.3%) | 1 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Arteriosclerosis coronary artery | 1/13 (7.7%) | 1 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Atrial fibrillation | 1/13 (7.7%) | 2 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 1/12 (8.3%) | 1 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 1/62 (1.6%) | 1 | 1/33 (3%) | 1 |
| Atrial flutter | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 1/12 (8.3%) | 1 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Cardiac failure congestive | 1/13 (7.7%) | 1 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/12 (8.3%) | 2 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 1/33 (3%) | 1 |
| Cardiac tamponade | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 1/59 (1.7%) | 1 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Cardiac ventricular thrombosis | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 1/62 (1.6%) | 1 | 0/33 (0%) | 0 |
| Cardiogenic shock | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/12 (8.3%) | 1 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Myocardial infarction | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 1/12 (8.3%) | 1 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 1/59 (1.7%) | 1 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Myocarditis | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/12 (8.3%) | 1 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Pericardial effusion | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 1/13 (7.7%) | 1 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/12 (8.3%) | 1 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Tachycardia | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 1/12 (8.3%) | 1 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Endocrine disorders | ||||||||||||||||||||||||||||
| Adrenal insufficiency | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/12 (8.3%) | 1 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Gastrointestinal disorders | ||||||||||||||||||||||||||||
| Abdominal pain | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 1/59 (1.7%) | 1 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Autoimmune colitis | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 1/11 (9.1%) | 1 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 1/12 (8.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Colitis | 0/13 (0%) | 0 | 1/12 (8.3%) | 1 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 1/12 (8.3%) | 1 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 1/33 (3%) | 2 |
| Constipation | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 1/33 (3%) | 1 |
| Diarrhoea | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 1/62 (1.6%) | 1 | 0/33 (0%) | 0 |
| Diarrhoea haemorrhagic | 0/13 (0%) | 0 | 1/12 (8.3%) | 1 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Diverticular perforation | 0/13 (0%) | 0 | 1/12 (8.3%) | 1 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 1/62 (1.6%) | 1 | 0/33 (0%) | 0 |
| Dysphagia | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 1/62 (1.6%) | 1 | 0/33 (0%) | 0 |
| Haematochezia | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 1/62 (1.6%) | 2 | 0/33 (0%) | 0 |
| Intestinal perforation | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Large intestine perforation | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 1/33 (3%) | 1 |
| Nausea | 1/13 (7.7%) | 1 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 1/59 (1.7%) | 1 | 1/62 (1.6%) | 1 | 0/33 (0%) | 0 |
| Pancreatitis | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 1/13 (7.7%) | 2 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/12 (8.3%) | 1 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Peptic ulcer | 1/13 (7.7%) | 1 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Retroperitoneal haematoma | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/12 (8.3%) | 1 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Small intestinal obstruction | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 1/11 (9.1%) | 1 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 1/59 (1.7%) | 1 | 2/62 (3.2%) | 2 | 0/33 (0%) | 0 |
| Vomiting | 1/13 (7.7%) | 1 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 1/59 (1.7%) | 3 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| General disorders | ||||||||||||||||||||||||||||
| Asthenia | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 1/59 (1.7%) | 1 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Death | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 1/11 (9.1%) | 1 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 2/12 (16.7%) | 2 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Fatigue | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 2/59 (3.4%) | 3 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Non-cardiac chest pain | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/12 (8.3%) | 1 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 1/59 (1.7%) | 1 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Pain | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 1/62 (1.6%) | 1 | 0/33 (0%) | 0 |
| Pyrexia | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 3/12 (25%) | 3 | 0/7 (0%) | 0 | 1/59 (1.7%) | 1 | 1/62 (1.6%) | 1 | 0/33 (0%) | 0 |
| Hepatobiliary disorders | ||||||||||||||||||||||||||||
| Hepatic function abnormal | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 1/13 (7.7%) | 1 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Hepatocellular injury | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 1/33 (3%) | 1 |
| Immune system disorders | ||||||||||||||||||||||||||||
| Anaphylactic reaction | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 1/59 (1.7%) | 1 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Drug hypersensitivity | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 1/13 (7.7%) | 2 | 1/12 (8.3%) | 1 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Hypersensitivity | 0/13 (0%) | 0 | 1/12 (8.3%) | 1 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Infections and infestations | ||||||||||||||||||||||||||||
| Bacteraemia | 1/13 (7.7%) | 1 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 1/7 (14.3%) | 1 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Cellulitis | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 1/12 (8.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 4/59 (6.8%) | 4 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Diverticulitis | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 1/11 (9.1%) | 1 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 1/62 (1.6%) | 1 | 0/33 (0%) | 0 |
| Gastroenteritis | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 1/62 (1.6%) | 1 | 1/33 (3%) | 1 |
| Infectious pleural effusion | 1/13 (7.7%) | 1 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Influenza | 1/13 (7.7%) | 1 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Periorbital cellulitis | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 1/62 (1.6%) | 1 | 0/33 (0%) | 0 |
| Pneumonia | 3/13 (23.1%) | 3 | 2/12 (16.7%) | 2 | 2/11 (18.2%) | 2 | 1/13 (7.7%) | 1 | 1/12 (8.3%) | 1 | 1/12 (8.3%) | 1 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 1/12 (8.3%) | 1 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 2/59 (3.4%) | 2 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Pyelonephritis acute | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 1/12 (8.3%) | 1 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Respiratory syncytial virus infection | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 1/11 (9.1%) | 1 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Sepsis | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 1/13 (7.7%) | 1 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 2/59 (3.4%) | 3 | 1/62 (1.6%) | 1 | 0/33 (0%) | 0 |
| Sepsis syndrome | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 1/59 (1.7%) | 1 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Septic shock | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 1/11 (9.1%) | 1 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Upper respiratory tract infection | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 1/59 (1.7%) | 1 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Urinary tract infection | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 1/59 (1.7%) | 1 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Urosepsis | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 1/59 (1.7%) | 1 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Injury, poisoning and procedural complications | ||||||||||||||||||||||||||||
| Radiation oesophagitis | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 1/12 (8.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Investigations | ||||||||||||||||||||||||||||
| Alanine aminotransferase increased | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 5/7 (71.4%) | 5 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 1/33 (3%) | 1 |
| Aspartate aminotransferase increased | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 1/12 (8.3%) | 1 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 5/7 (71.4%) | 5 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 1/33 (3%) | 1 |
| Blood pressure increased | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 1/11 (9.1%) | 1 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Liver function test increased | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 1/12 (8.3%) | 1 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Transaminases increased | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 1/59 (1.7%) | 1 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| White blood cell count decreased | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 1/13 (7.7%) | 1 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Metabolism and nutrition disorders | ||||||||||||||||||||||||||||
| Dehydration | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 1/12 (8.3%) | 1 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/12 (8.3%) | 1 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 1/59 (1.7%) | 1 | 1/62 (1.6%) | 1 | 0/33 (0%) | 0 |
| Diabetic ketoacidosis | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 1/33 (3%) | 1 |
| Musculoskeletal and connective tissue disorders | ||||||||||||||||||||||||||||
| Back pain | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 1/62 (1.6%) | 1 | 0/33 (0%) | 0 |
| Flank pain | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 1/62 (1.6%) | 1 | 0/33 (0%) | 0 |
| Musculoskeletal pain | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 1/62 (1.6%) | 1 | 0/33 (0%) | 0 |
| Neck pain | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 1/12 (8.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||||||||||||||||||||||
| Malignant pleural effusion | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 1/59 (1.7%) | 1 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Small cell lung cancer | 1/13 (7.7%) | 1 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Nervous system disorders | ||||||||||||||||||||||||||||
| Cerebrovascular accident | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 1/62 (1.6%) | 1 | 0/33 (0%) | 0 |
| Cerebrovascular disorder | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 1/59 (1.7%) | 1 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Encephalopathy | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 1/59 (1.7%) | 1 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Haemorrhage intracranial | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 1/59 (1.7%) | 1 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Headache | 0/13 (0%) | 0 | 1/12 (8.3%) | 1 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Neuralgic amyotrophy | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 1/12 (8.3%) | 1 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Syncope | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 1/62 (1.6%) | 1 | 1/33 (3%) | 1 |
| Transient ischaemic attack | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 1/62 (1.6%) | 1 | 0/33 (0%) | 0 |
| Psychiatric disorders | ||||||||||||||||||||||||||||
| Depression | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 1/59 (1.7%) | 1 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Mental status changes | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 1/59 (1.7%) | 1 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Renal and urinary disorders | ||||||||||||||||||||||||||||
| Acute kidney injury | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 6/59 (10.2%) | 6 | 1/62 (1.6%) | 1 | 0/33 (0%) | 0 |
| Respiratory, thoracic and mediastinal disorders | ||||||||||||||||||||||||||||
| Acute respiratory failure | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 1/12 (8.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Chronic obstructive pulmonary disease | 1/13 (7.7%) | 2 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 2/12 (16.7%) | 2 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 1/62 (1.6%) | 3 | 1/33 (3%) | 1 |
| Dyspnoea | 1/13 (7.7%) | 1 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 1/12 (8.3%) | 1 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 1/59 (1.7%) | 1 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Haemoptysis | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 1/59 (1.7%) | 1 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Hypoxia | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 1/33 (3%) | 1 |
| Lung infiltration | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 1/59 (1.7%) | 1 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Pleural effusion | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 3/59 (5.1%) | 3 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Pneumonia aspiration | 1/13 (7.7%) | 1 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Pneumonitis | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 1/11 (9.1%) | 1 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 1/59 (1.7%) | 1 | 0/62 (0%) | 0 | 2/33 (6.1%) | 2 |
| Pneumothorax | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 1/62 (1.6%) | 1 | 0/33 (0%) | 0 |
| Pulmonary embolism | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 1/11 (9.1%) | 1 | 1/13 (7.7%) | 1 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/12 (8.3%) | 1 | 1/12 (8.3%) | 1 | 0/7 (0%) | 0 | 1/59 (1.7%) | 1 | 1/62 (1.6%) | 1 | 0/33 (0%) | 0 |
| Skin and subcutaneous tissue disorders | ||||||||||||||||||||||||||||
| Rash | 1/13 (7.7%) | 1 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 1/12 (8.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 1/59 (1.7%) | 1 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Rash maculo-papular | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 1/12 (8.3%) | 1 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Urticaria | 1/13 (7.7%) | 1 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Vascular disorders | ||||||||||||||||||||||||||||
| Aortic stenosis | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/12 (8.3%) | 1 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Deep vein thrombosis | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 1/13 (7.7%) | 1 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Embolism | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 1/59 (1.7%) | 1 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
Other (Not Including Serious) Adverse Events |
||||||||||||||||||||||||||||
| Part1CohortA2 (Pembro 2mg/kg+Paclitaxel [Pa]+Carboplatin [C]) | Part1 CohortA10 (Pembro10mg/kg+Pa+C) | Part 1 Cohort B2 (Pembro 2mg/kg+Pa+C+Bevacizumab [B]) | Part 1 Cohort B10 (Pembro 10 mg/kg+Pa+C+B) | Part 1 Cohort C2 (Pembro 2 mg/kg+Pemetrexed [Pe]+C) | Part 1 Cohort C10 (Pembro 10 mg/kg+Pe+C) | Part 1 Cohort D1 (Pembro 10 mg/kg+Ipilimumab [I]) | Part 1 Cohort D2 (Pembro 10 mg/kg+I) | Part 1 Cohort D4 (Pembro 2 mg/kg+I) | Part 1 Cohort E (Pembro 2 mg/kg+Erlotinib) | Part 1 Cohort F (Pembro 2 mg/kg+Gefitinib) | Part 2 Cohort G+ (Pembro 200 mg+Pe+C) | Part 2 Cohort G- (Placebo+Pe+C) | Part 2 Cohort H (Pembro 2mg/kg+I) | |||||||||||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 13/13 (100%) | 12/12 (100%) | 11/11 (100%) | 12/13 (92.3%) | 12/12 (100%) | 12/12 (100%) | 3/3 (100%) | 3/3 (100%) | 12/12 (100%) | 12/12 (100%) | 6/7 (85.7%) | 58/59 (98.3%) | 60/62 (96.8%) | 30/33 (90.9%) | ||||||||||||||
| Blood and lymphatic system disorders | ||||||||||||||||||||||||||||
| Anaemia | 5/13 (38.5%) | 7 | 4/12 (33.3%) | 4 | 2/11 (18.2%) | 2 | 5/13 (38.5%) | 6 | 3/12 (25%) | 3 | 6/12 (50%) | 7 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 1/12 (8.3%) | 1 | 0/7 (0%) | 0 | 21/59 (35.6%) | 28 | 35/62 (56.5%) | 43 | 0/33 (0%) | 0 |
| Febrile neutropenia | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 1/12 (8.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Increased tendency to bruise | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 1/12 (8.3%) | 1 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Leukopenia | 2/13 (15.4%) | 2 | 0/12 (0%) | 0 | 1/11 (9.1%) | 1 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 2/12 (16.7%) | 2 | 0/7 (0%) | 0 | 1/59 (1.7%) | 1 | 2/62 (3.2%) | 2 | 0/33 (0%) | 0 |
| Lymphadenopathy | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/12 (8.3%) | 1 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Neutropenia | 2/13 (15.4%) | 2 | 1/12 (8.3%) | 1 | 2/11 (18.2%) | 2 | 1/13 (7.7%) | 1 | 2/12 (16.7%) | 2 | 1/12 (8.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 1/12 (8.3%) | 1 | 0/7 (0%) | 0 | 5/59 (8.5%) | 6 | 7/62 (11.3%) | 8 | 0/33 (0%) | 0 |
| Thrombocytopenia | 1/13 (7.7%) | 1 | 4/12 (33.3%) | 5 | 1/11 (9.1%) | 1 | 2/13 (15.4%) | 3 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/12 (8.3%) | 1 | 1/12 (8.3%) | 1 | 0/7 (0%) | 0 | 2/59 (3.4%) | 4 | 3/62 (4.8%) | 3 | 0/33 (0%) | 0 |
| Cardiac disorders | ||||||||||||||||||||||||||||
| Atrial fibrillation | 1/13 (7.7%) | 1 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 1/12 (8.3%) | 1 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 1/33 (3%) | 1 |
| Atrioventricular block second degree | 1/13 (7.7%) | 1 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Cardiac failure congestive | 1/13 (7.7%) | 1 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Cardiac ventricular thrombosis | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/12 (8.3%) | 1 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Diastolic dysfunction | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 1/12 (8.3%) | 1 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Myocardial infarction | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 1/13 (7.7%) | 1 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Palpitations | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 1/11 (9.1%) | 1 | 1/13 (7.7%) | 1 | 1/12 (8.3%) | 1 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 2/59 (3.4%) | 2 | 1/62 (1.6%) | 1 | 0/33 (0%) | 0 |
| Tachycardia | 0/13 (0%) | 0 | 1/12 (8.3%) | 1 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 2/12 (16.7%) | 2 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 3/59 (5.1%) | 3 | 0/62 (0%) | 0 | 1/33 (3%) | 1 |
| Ear and labyrinth disorders | ||||||||||||||||||||||||||||
| Deafness | 0/13 (0%) | 0 | 1/12 (8.3%) | 1 | 1/11 (9.1%) | 1 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 1/12 (8.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 1/59 (1.7%) | 1 | 1/62 (1.6%) | 1 | 0/33 (0%) | 0 |
| Ear pain | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 1/12 (8.3%) | 1 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/12 (8.3%) | 1 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 1/59 (1.7%) | 1 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Hypoacusis | 1/13 (7.7%) | 1 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 1/12 (8.3%) | 1 | 2/12 (16.7%) | 2 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/12 (8.3%) | 1 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 2/59 (3.4%) | 2 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Tinnitus | 1/13 (7.7%) | 1 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 1/12 (8.3%) | 1 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 1/12 (8.3%) | 1 | 0/7 (0%) | 0 | 1/59 (1.7%) | 1 | 1/62 (1.6%) | 1 | 0/33 (0%) | 0 |
| Vertigo | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 1/13 (7.7%) | 1 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 4/59 (6.8%) | 9 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Endocrine disorders | ||||||||||||||||||||||||||||
| Adrenal insufficiency | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 1/12 (8.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Autoimmune thyroiditis | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/12 (8.3%) | 1 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Cushingoid | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 1/12 (8.3%) | 1 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Hyperparathyroidism | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 1/12 (8.3%) | 1 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Hyperthyroidism | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 1/13 (7.7%) | 1 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/12 (8.3%) | 1 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 5/59 (8.5%) | 6 | 1/62 (1.6%) | 1 | 1/33 (3%) | 1 |
| Hypogonadism | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 1/11 (9.1%) | 1 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Hypothyroidism | 2/13 (15.4%) | 3 | 0/12 (0%) | 0 | 4/11 (36.4%) | 4 | 1/13 (7.7%) | 2 | 2/12 (16.7%) | 2 | 2/12 (16.7%) | 2 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 2/12 (16.7%) | 2 | 4/12 (33.3%) | 4 | 0/7 (0%) | 0 | 7/59 (11.9%) | 8 | 3/62 (4.8%) | 3 | 9/33 (27.3%) | 9 |
| Thyroiditis | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 1/11 (9.1%) | 1 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/12 (8.3%) | 1 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 2/33 (6.1%) | 2 |
| Eye disorders | ||||||||||||||||||||||||||||
| Asthenopia | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 1/12 (8.3%) | 1 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Blepharitis | 1/13 (7.7%) | 2 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 2/59 (3.4%) | 2 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Cataract | 1/13 (7.7%) | 1 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 1/12 (8.3%) | 1 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 1/12 (8.3%) | 1 | 0/7 (0%) | 0 | 1/59 (1.7%) | 1 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Corneal erosion | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 1/12 (8.3%) | 1 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Cystoid macular oedema | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 1/12 (8.3%) | 1 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Dry eye | 1/13 (7.7%) | 1 | 0/12 (0%) | 0 | 1/11 (9.1%) | 1 | 1/13 (7.7%) | 1 | 1/12 (8.3%) | 1 | 2/12 (16.7%) | 2 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 3/12 (25%) | 3 | 1/7 (14.3%) | 1 | 9/59 (15.3%) | 9 | 1/62 (1.6%) | 1 | 0/33 (0%) | 0 |
| Eye discharge | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 3/59 (5.1%) | 3 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Eye disorder | 1/13 (7.7%) | 1 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 2/59 (3.4%) | 2 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Eye irritation | 1/13 (7.7%) | 1 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 1/59 (1.7%) | 1 | 1/62 (1.6%) | 1 | 0/33 (0%) | 0 |
| Eye pruritus | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 1/12 (8.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Eye swelling | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 3/59 (5.1%) | 3 | 2/62 (3.2%) | 2 | 0/33 (0%) | 0 |
| Eyelid disorder | 1/13 (7.7%) | 1 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Eyelid rash | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 1/12 (8.3%) | 1 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Glaucoma | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 1/12 (8.3%) | 1 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Iritis | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 1/13 (7.7%) | 1 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Lacrimation increased | 1/13 (7.7%) | 1 | 0/12 (0%) | 0 | 1/11 (9.1%) | 1 | 1/13 (7.7%) | 1 | 1/12 (8.3%) | 1 | 2/12 (16.7%) | 3 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/12 (8.3%) | 1 | 1/12 (8.3%) | 1 | 0/7 (0%) | 0 | 11/59 (18.6%) | 12 | 8/62 (12.9%) | 9 | 1/33 (3%) | 1 |
| Periorbital oedema | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 1/12 (8.3%) | 1 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 2/62 (3.2%) | 2 | 0/33 (0%) | 0 |
| Uveitis | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/12 (0%) | 0 | 1/12 (8.3%) | 1 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Vision blurred | 0/13 (0%) | 0 | 2/12 (16.7%) | 2 | 2/11 (18.2%) | 2 | 0/13 (0%) | 0 | 1/12 (8.3%) | 1 | 1/12 (8.3%) | 1 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 5/59 (8.5%) | 5 | 5/62 (8.1%) | 5 | 1/33 (3%) | 1 |
| Visual impairment | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 1/12 (8.3%) | 1 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/12 (8.3%) | 1 | 1/12 (8.3%) | 1 | 0/7 (0%) | 0 | 1/59 (1.7%) | 1 | 1/62 (1.6%) | 1 | 1/33 (3%) | 1 |
| Vitreous floaters | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 1/12 (8.3%) | 1 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 2/33 (6.1%) | 2 |
| Gastrointestinal disorders | ||||||||||||||||||||||||||||
| Abdominal discomfort | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 1/12 (8.3%) | 1 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 1/62 (1.6%) | 1 | 1/33 (3%) | 1 |
| Abdominal distension | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 1/12 (8.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 1/7 (14.3%) | 1 | 3/59 (5.1%) | 4 | 4/62 (6.5%) | 4 | 0/33 (0%) | 0 |
| Abdominal pain | 2/13 (15.4%) | 2 | 3/12 (25%) | 3 | 1/11 (9.1%) | 1 | 1/13 (7.7%) | 1 | 1/12 (8.3%) | 1 | 1/12 (8.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 3/12 (25%) | 3 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 7/59 (11.9%) | 8 | 2/62 (3.2%) | 2 | 1/33 (3%) | 1 |
| Abdominal pain upper | 1/13 (7.7%) | 2 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 1/12 (8.3%) | 1 | 1/12 (8.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/12 (8.3%) | 1 | 0/12 (0%) | 0 | 1/7 (14.3%) | 1 | 4/59 (6.8%) | 4 | 0/62 (0%) | 0 | 2/33 (6.1%) | 2 |
| Anal haemorrhage | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 1/12 (8.3%) | 1 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Anorectal discomfort | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 1/11 (9.1%) | 1 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Ascites | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 1/12 (8.3%) | 1 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Chapped lips | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 1/12 (8.3%) | 1 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Cheilitis | 0/13 (0%) | 0 | 1/12 (8.3%) | 1 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Colitis | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 1/13 (7.7%) | 1 | 1/12 (8.3%) | 1 | 1/12 (8.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 1/12 (8.3%) | 1 | 0/7 (0%) | 0 | 1/59 (1.7%) | 1 | 0/62 (0%) | 0 | 1/33 (3%) | 2 |
| Constipation | 8/13 (61.5%) | 9 | 7/12 (58.3%) | 7 | 9/11 (81.8%) | 9 | 5/13 (38.5%) | 6 | 8/12 (66.7%) | 8 | 7/12 (58.3%) | 9 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 5/12 (41.7%) | 5 | 2/12 (16.7%) | 2 | 0/7 (0%) | 0 | 31/59 (52.5%) | 38 | 23/62 (37.1%) | 28 | 9/33 (27.3%) | 10 |
| Diarrhoea | 4/13 (30.8%) | 7 | 2/12 (16.7%) | 6 | 3/11 (27.3%) | 4 | 5/13 (38.5%) | 8 | 4/12 (33.3%) | 4 | 4/12 (33.3%) | 4 | 1/3 (33.3%) | 1 | 1/3 (33.3%) | 1 | 2/12 (16.7%) | 3 | 7/12 (58.3%) | 10 | 4/7 (57.1%) | 5 | 23/59 (39%) | 30 | 16/62 (25.8%) | 28 | 6/33 (18.2%) | 8 |
| Dry mouth | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 1/11 (9.1%) | 1 | 0/13 (0%) | 0 | 2/12 (16.7%) | 2 | 1/12 (8.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/12 (8.3%) | 1 | 2/12 (16.7%) | 2 | 0/7 (0%) | 0 | 4/59 (6.8%) | 7 | 4/62 (6.5%) | 4 | 2/33 (6.1%) | 2 |
| Dyspepsia | 0/13 (0%) | 0 | 1/12 (8.3%) | 1 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 1/12 (8.3%) | 1 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 1/12 (8.3%) | 1 | 0/7 (0%) | 0 | 7/59 (11.9%) | 11 | 2/62 (3.2%) | 3 | 1/33 (3%) | 1 |
| Dysphagia | 2/13 (15.4%) | 2 | 0/12 (0%) | 0 | 1/11 (9.1%) | 1 | 0/13 (0%) | 0 | 2/12 (16.7%) | 2 | 1/12 (8.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 1/59 (1.7%) | 1 | 4/62 (6.5%) | 4 | 2/33 (6.1%) | 2 |
| Enterocolitis | 1/13 (7.7%) | 1 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Flatulence | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 1/12 (8.3%) | 1 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 2/59 (3.4%) | 2 | 2/62 (3.2%) | 4 | 0/33 (0%) | 0 |
| Gastric ulcer | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 1/7 (14.3%) | 1 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Gastritis | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 1/13 (7.7%) | 1 | 0/12 (0%) | 0 | 1/12 (8.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 1/33 (3%) | 2 |
| Gastrooesophageal reflux disease | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 1/11 (9.1%) | 2 | 1/13 (7.7%) | 1 | 1/12 (8.3%) | 2 | 0/12 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 1/12 (8.3%) | 1 | 2/12 (16.7%) | 2 | 1/7 (14.3%) | 1 | 5/59 (8.5%) | 7 | 2/62 (3.2%) | 2 | 0/33 (0%) | 0 |
| Gingival bleeding | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 1/11 (9.1%) | 1 | 1/13 (7.7%) | 2 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Gingival pain | 1/13 (7.7%) | 1 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Haematemesis | 0/13 (0%) | 0 | 1/12 (8.3%) | 1 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Haematochezia | 0/13 (0%) | 0 | 1/12 (8.3%) | 1 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 1/12 (8.3%) | 1 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Haemorrhoids | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 1/13 (7.7%) | 1 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Hyperchlorhydria | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 1/12 (8.3%) | 1 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Lip disorder | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 1/12 (8.3%) | 1 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Mouth ulceration | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 1/7 (14.3%) | 1 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Nausea | 7/13 (53.8%) | 11 | 4/12 (33.3%) | 5 | 7/11 (63.6%) | 8 | 6/13 (46.2%) | 7 | 7/12 (58.3%) | 7 | 5/12 (41.7%) | 5 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 4/12 (33.3%) | 6 | 3/12 (25%) | 3 | 1/7 (14.3%) | 1 | 42/59 (71.2%) | 75 | 34/62 (54.8%) | 46 | 7/33 (21.2%) | 9 |
| Oral dysaesthesia | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 1/13 (7.7%) | 1 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Oral pain | 1/13 (7.7%) | 1 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 1/12 (8.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 2/59 (3.4%) | 2 | 2/62 (3.2%) | 2 | 3/33 (9.1%) | 3 |
| Oral papule | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 1/12 (8.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Proctalgia | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 1/13 (7.7%) | 1 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Rectal polyp | 1/13 (7.7%) | 1 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Rectal ulcer | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 1/13 (7.7%) | 1 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Stomatitis | 0/13 (0%) | 0 | 1/12 (8.3%) | 1 | 2/11 (18.2%) | 2 | 3/13 (23.1%) | 3 | 2/12 (16.7%) | 3 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 2/12 (16.7%) | 2 | 0/7 (0%) | 0 | 4/59 (6.8%) | 15 | 5/62 (8.1%) | 8 | 0/33 (0%) | 0 |
| Tongue discolouration | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 1/12 (8.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Toothache | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 2/11 (18.2%) | 2 | 0/13 (0%) | 0 | 1/12 (8.3%) | 1 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/12 (8.3%) | 1 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 2/33 (6.1%) | 3 |
| Vomiting | 1/13 (7.7%) | 2 | 2/12 (16.7%) | 2 | 4/11 (36.4%) | 4 | 2/13 (15.4%) | 3 | 0/12 (0%) | 0 | 2/12 (16.7%) | 2 | 1/3 (33.3%) | 2 | 1/3 (33.3%) | 1 | 5/12 (41.7%) | 7 | 2/12 (16.7%) | 4 | 1/7 (14.3%) | 1 | 25/59 (42.4%) | 44 | 17/62 (27.4%) | 18 | 8/33 (24.2%) | 9 |
| General disorders | ||||||||||||||||||||||||||||
| Asthenia | 1/13 (7.7%) | 1 | 0/12 (0%) | 0 | 1/11 (9.1%) | 1 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 1/7 (14.3%) | 1 | 1/59 (1.7%) | 1 | 4/62 (6.5%) | 4 | 1/33 (3%) | 1 |
| Catheter site pain | 1/13 (7.7%) | 1 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 1/59 (1.7%) | 1 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Chest discomfort | 1/13 (7.7%) | 2 | 1/12 (8.3%) | 1 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 1/12 (8.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 2/12 (16.7%) | 3 | 0/7 (0%) | 0 | 2/59 (3.4%) | 2 | 0/62 (0%) | 0 | 1/33 (3%) | 1 |
| Chest pain | 3/13 (23.1%) | 5 | 0/12 (0%) | 0 | 1/11 (9.1%) | 1 | 2/13 (15.4%) | 2 | 0/12 (0%) | 0 | 1/12 (8.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 2/12 (16.7%) | 2 | 1/12 (8.3%) | 1 | 0/7 (0%) | 0 | 1/59 (1.7%) | 1 | 5/62 (8.1%) | 5 | 0/33 (0%) | 0 |
| Chills | 2/13 (15.4%) | 2 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 2/13 (15.4%) | 2 | 1/12 (8.3%) | 2 | 0/12 (0%) | 0 | 2/3 (66.7%) | 2 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 2/12 (16.7%) | 2 | 0/7 (0%) | 0 | 4/59 (6.8%) | 5 | 2/62 (3.2%) | 2 | 0/33 (0%) | 0 |
| Face oedema | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 3/12 (25%) | 3 | 1/12 (8.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 1/59 (1.7%) | 1 | 1/62 (1.6%) | 1 | 0/33 (0%) | 0 |
| Facial pain | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 1/12 (8.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Fatigue | 8/13 (61.5%) | 12 | 8/12 (66.7%) | 8 | 8/11 (72.7%) | 8 | 5/13 (38.5%) | 5 | 6/12 (50%) | 6 | 11/12 (91.7%) | 11 | 2/3 (66.7%) | 2 | 3/3 (100%) | 3 | 4/12 (33.3%) | 5 | 7/12 (58.3%) | 7 | 0/7 (0%) | 0 | 40/59 (67.8%) | 68 | 33/62 (53.2%) | 39 | 16/33 (48.5%) | 21 |
| Feeling cold | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 1/12 (8.3%) | 1 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Gait disturbance | 1/13 (7.7%) | 1 | 0/12 (0%) | 0 | 1/11 (9.1%) | 1 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/12 (8.3%) | 1 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 1/59 (1.7%) | 1 | 3/62 (4.8%) | 3 | 1/33 (3%) | 1 |
| Generalised oedema | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 1/12 (8.3%) | 1 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 1/62 (1.6%) | 1 | 0/33 (0%) | 0 |
| Influenza like illness | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 1/12 (8.3%) | 2 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/12 (8.3%) | 1 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 2/59 (3.4%) | 2 | 1/62 (1.6%) | 1 | 0/33 (0%) | 0 |
| Infusion site phlebitis | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 1/12 (8.3%) | 1 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Localised oedema | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 3/59 (5.1%) | 3 | 1/62 (1.6%) | 1 | 0/33 (0%) | 0 |
| Malaise | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 1/13 (7.7%) | 1 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 1/7 (14.3%) | 1 | 3/59 (5.1%) | 3 | 2/62 (3.2%) | 5 | 0/33 (0%) | 0 |
| Mucosal inflammation | 1/13 (7.7%) | 1 | 0/12 (0%) | 0 | 2/11 (18.2%) | 2 | 1/13 (7.7%) | 1 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/12 (8.3%) | 1 | 1/12 (8.3%) | 1 | 0/7 (0%) | 0 | 5/59 (8.5%) | 5 | 1/62 (1.6%) | 3 | 2/33 (6.1%) | 2 |
| Non-cardiac chest pain | 1/13 (7.7%) | 1 | 0/12 (0%) | 0 | 1/11 (9.1%) | 1 | 1/13 (7.7%) | 1 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 5/59 (8.5%) | 6 | 0/62 (0%) | 0 | 1/33 (3%) | 1 |
| Oedema | 1/13 (7.7%) | 1 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 1/13 (7.7%) | 1 | 0/12 (0%) | 0 | 1/12 (8.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 3/59 (5.1%) | 4 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Oedema peripheral | 4/13 (30.8%) | 6 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 1/13 (7.7%) | 2 | 3/12 (25%) | 5 | 3/12 (25%) | 5 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 1/12 (8.3%) | 1 | 2/12 (16.7%) | 2 | 0/7 (0%) | 0 | 14/59 (23.7%) | 18 | 13/62 (21%) | 15 | 2/33 (6.1%) | 2 |
| Pain | 0/13 (0%) | 0 | 3/12 (25%) | 3 | 1/11 (9.1%) | 1 | 2/13 (15.4%) | 2 | 1/12 (8.3%) | 1 | 0/12 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 1/12 (8.3%) | 1 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 1/59 (1.7%) | 1 | 2/62 (3.2%) | 3 | 2/33 (6.1%) | 2 |
| Peripheral swelling | 1/13 (7.7%) | 1 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 1/12 (8.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Pyrexia | 4/13 (30.8%) | 6 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 3/13 (23.1%) | 4 | 0/12 (0%) | 0 | 2/12 (16.7%) | 2 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 1/12 (8.3%) | 1 | 4/12 (33.3%) | 5 | 1/7 (14.3%) | 1 | 5/59 (8.5%) | 9 | 3/62 (4.8%) | 3 | 3/33 (9.1%) | 3 |
| Temperature intolerance | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 1/12 (8.3%) | 1 | 0/7 (0%) | 0 | 2/59 (3.4%) | 2 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Xerosis | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 1/12 (8.3%) | 2 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Hepatobiliary disorders | ||||||||||||||||||||||||||||
| Autoimmune hepatitis | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 1/12 (8.3%) | 1 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Jaundice | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 1/7 (14.3%) | 1 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Immune system disorders | ||||||||||||||||||||||||||||
| Drug hypersensitivity | 0/13 (0%) | 0 | 1/12 (8.3%) | 1 | 0/11 (0%) | 0 | 1/13 (7.7%) | 1 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Hypersensitivity | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 2/13 (15.4%) | 2 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 1/62 (1.6%) | 1 | 0/33 (0%) | 0 |
| Seasonal allergy | 1/13 (7.7%) | 1 | 1/12 (8.3%) | 1 | 0/11 (0%) | 0 | 1/13 (7.7%) | 1 | 0/12 (0%) | 0 | 1/12 (8.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 1/59 (1.7%) | 1 | 1/62 (1.6%) | 1 | 0/33 (0%) | 0 |
| Infections and infestations | ||||||||||||||||||||||||||||
| Bacteraemia | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 1/7 (14.3%) | 1 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Bronchitis | 1/13 (7.7%) | 1 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 2/12 (16.7%) | 2 | 0/7 (0%) | 0 | 3/59 (5.1%) | 3 | 0/62 (0%) | 0 | 2/33 (6.1%) | 2 |
| Candida infection | 1/13 (7.7%) | 1 | 0/12 (0%) | 0 | 1/11 (9.1%) | 1 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 1/59 (1.7%) | 1 | 1/62 (1.6%) | 1 | 1/33 (3%) | 1 |
| Cellulitis | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 1/12 (8.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 1/12 (8.3%) | 1 | 0/7 (0%) | 0 | 3/59 (5.1%) | 9 | 1/62 (1.6%) | 1 | 1/33 (3%) | 1 |
| Conjunctivitis | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/12 (8.3%) | 1 | 1/12 (8.3%) | 2 | 1/7 (14.3%) | 1 | 7/59 (11.9%) | 10 | 2/62 (3.2%) | 2 | 0/33 (0%) | 0 |
| Cystitis | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 1/11 (9.1%) | 1 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Cystitis escherichia | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 1/11 (9.1%) | 1 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Diverticulitis | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 1/11 (9.1%) | 1 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 1/59 (1.7%) | 1 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Eye infection | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 1/12 (8.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Folliculitis | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 1/12 (8.3%) | 1 | 1/7 (14.3%) | 1 | 0/59 (0%) | 0 | 1/62 (1.6%) | 1 | 0/33 (0%) | 0 |
| Fungal infection | 1/13 (7.7%) | 1 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 1/59 (1.7%) | 2 | 1/62 (1.6%) | 1 | 0/33 (0%) | 0 |
| Fungal skin infection | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 1/12 (8.3%) | 2 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 1/33 (3%) | 1 |
| Furuncle | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 1/13 (7.7%) | 1 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 1/12 (8.3%) | 2 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Gastroenteritis viral | 1/13 (7.7%) | 1 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 1/59 (1.7%) | 1 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Giardiasis | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 1/12 (8.3%) | 1 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Gingival abscess | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 1/12 (8.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Herpes zoster | 2/13 (15.4%) | 2 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 1/7 (14.3%) | 1 | 2/59 (3.4%) | 2 | 3/62 (4.8%) | 3 | 0/33 (0%) | 0 |
| Hordeolum | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 1/13 (7.7%) | 1 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 1/59 (1.7%) | 1 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Influenza | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 1/12 (8.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Laryngitis | 1/13 (7.7%) | 1 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Mucosal infection | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 1/12 (8.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 1/59 (1.7%) | 1 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Nasopharyngitis | 1/13 (7.7%) | 3 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 1/12 (8.3%) | 1 | 0/7 (0%) | 0 | 1/59 (1.7%) | 1 | 2/62 (3.2%) | 2 | 2/33 (6.1%) | 2 |
| Oral candidiasis | 1/13 (7.7%) | 1 | 0/12 (0%) | 0 | 1/11 (9.1%) | 2 | 2/13 (15.4%) | 2 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 1/12 (8.3%) | 2 | 0/7 (0%) | 0 | 1/59 (1.7%) | 1 | 2/62 (3.2%) | 2 | 0/33 (0%) | 0 |
| Oral herpes | 0/13 (0%) | 0 | 1/12 (8.3%) | 1 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/12 (8.3%) | 1 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 1/59 (1.7%) | 1 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Paronychia | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 1/12 (8.3%) | 1 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Pharyngitis | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 1/11 (9.1%) | 1 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Pneumonia | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 1/11 (9.1%) | 1 | 2/13 (15.4%) | 2 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/12 (8.3%) | 1 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 2/59 (3.4%) | 2 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Pneumonia bacterial | 1/13 (7.7%) | 1 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Rash pustular | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 1/12 (8.3%) | 3 | 0/7 (0%) | 0 | 1/59 (1.7%) | 1 | 0/62 (0%) | 0 | 1/33 (3%) | 1 |
| Respiratory tract infection | 1/13 (7.7%) | 1 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Respiratory tract infection viral | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 1/13 (7.7%) | 1 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Rhinitis | 2/13 (15.4%) | 2 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 3/59 (5.1%) | 4 | 6/62 (9.7%) | 7 | 1/33 (3%) | 1 |
| Sinusitis | 0/13 (0%) | 0 | 1/12 (8.3%) | 1 | 2/11 (18.2%) | 3 | 1/13 (7.7%) | 1 | 1/12 (8.3%) | 3 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 1/12 (8.3%) | 1 | 0/7 (0%) | 0 | 5/59 (8.5%) | 6 | 1/62 (1.6%) | 1 | 1/33 (3%) | 1 |
| Skin bacterial infection | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 2/12 (16.7%) | 2 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Skin infection | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 1/12 (8.3%) | 1 | 1/12 (8.3%) | 1 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 2/59 (3.4%) | 3 | 1/62 (1.6%) | 1 | 1/33 (3%) | 1 |
| Subcutaneous abscess | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 1/13 (7.7%) | 1 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Tooth infection | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 1/13 (7.7%) | 1 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 1/59 (1.7%) | 1 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Upper respiratory tract infection | 2/13 (15.4%) | 2 | 1/12 (8.3%) | 2 | 3/11 (27.3%) | 4 | 1/13 (7.7%) | 1 | 3/12 (25%) | 4 | 3/12 (25%) | 5 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 2/12 (16.7%) | 2 | 3/12 (25%) | 7 | 0/7 (0%) | 0 | 14/59 (23.7%) | 15 | 3/62 (4.8%) | 3 | 1/33 (3%) | 1 |
| Urinary tract infection | 1/13 (7.7%) | 1 | 2/12 (16.7%) | 2 | 1/11 (9.1%) | 1 | 0/13 (0%) | 0 | 1/12 (8.3%) | 1 | 3/12 (25%) | 4 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/12 (0%) | 0 | 2/12 (16.7%) | 3 | 0/7 (0%) | 0 | 7/59 (11.9%) | 8 | 2/62 (3.2%) | 4 | 3/33 (9.1%) | 3 |
| Viral infection | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 1/11 (9.1%) | 1 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Vulvovaginal mycotic infection | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 1/13 (7.7%) | 2 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 1/59 (1.7%) | 1 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Injury, poisoning and procedural complications | ||||||||||||||||||||||||||||
| Arthropod bite | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/12 (8.3%) | 1 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Contusion | 0/13 (0%) | 0 | 1/12 (8.3%) | 1 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/12 (8.3%) | 1 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 3/59 (5.1%) | 3 | 1/62 (1.6%) | 1 | 1/33 (3%) | 1 |
| Fall | 1/13 (7.7%) | 1 | 0/12 (0%) | 0 | 1/11 (9.1%) | 1 | 0/13 (0%) | 0 | 1/12 (8.3%) | 1 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 7/59 (11.9%) | 7 | 2/62 (3.2%) | 2 | 3/33 (9.1%) | 3 |
| Foot fracture | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 1/11 (9.1%) | 1 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Laceration | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 1/12 (8.3%) | 1 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 3/59 (5.1%) | 3 | 1/62 (1.6%) | 1 | 0/33 (0%) | 0 |
| Radius fracture | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 2/33 (6.1%) | 2 |
| Tooth fracture | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 1/12 (8.3%) | 1 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/12 (8.3%) | 1 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 1/59 (1.7%) | 1 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Wound | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 1/12 (8.3%) | 1 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Investigations | ||||||||||||||||||||||||||||
| Alanine aminotransferase increased | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 2/13 (15.4%) | 2 | 4/12 (33.3%) | 8 | 4/12 (33.3%) | 4 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 4/12 (33.3%) | 5 | 0/7 (0%) | 0 | 10/59 (16.9%) | 12 | 10/62 (16.1%) | 14 | 1/33 (3%) | 1 |
| Aspartate aminotransferase increased | 1/13 (7.7%) | 1 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 2/13 (15.4%) | 3 | 3/12 (25%) | 7 | 3/12 (25%) | 3 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/12 (8.3%) | 1 | 4/12 (33.3%) | 5 | 0/7 (0%) | 0 | 11/59 (18.6%) | 13 | 13/62 (21%) | 17 | 1/33 (3%) | 1 |
| Bilirubin conjugated increased | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 1/11 (9.1%) | 1 | 1/13 (7.7%) | 1 | 0/12 (0%) | 0 | 1/12 (8.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Blood alkaline phosphatase increased | 1/13 (7.7%) | 1 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 1/13 (7.7%) | 2 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 3/59 (5.1%) | 4 | 6/62 (9.7%) | 6 | 2/33 (6.1%) | 2 |
| Blood bilirubin increased | 2/13 (15.4%) | 2 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/12 (8.3%) | 1 | 2/12 (16.7%) | 2 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 1/33 (3%) | 1 |
| Blood cholesterol increased | 2/13 (15.4%) | 3 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 2/13 (15.4%) | 2 | 0/12 (0%) | 0 | 1/12 (8.3%) | 2 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Blood creatinine increased | 1/13 (7.7%) | 1 | 0/12 (0%) | 0 | 2/11 (18.2%) | 4 | 0/13 (0%) | 0 | 1/12 (8.3%) | 1 | 4/12 (33.3%) | 4 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/12 (8.3%) | 1 | 2/12 (16.7%) | 2 | 0/7 (0%) | 0 | 12/59 (20.3%) | 13 | 5/62 (8.1%) | 6 | 2/33 (6.1%) | 2 |
| Blood glucose increased | 1/13 (7.7%) | 1 | 0/12 (0%) | 0 | 1/11 (9.1%) | 1 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/12 (8.3%) | 1 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 1/59 (1.7%) | 1 | 1/62 (1.6%) | 2 | 1/33 (3%) | 1 |
| Blood magnesium decreased | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 1/11 (9.1%) | 1 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Blood phosphorus decreased | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 1/12 (8.3%) | 1 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Blood potassium increased | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 1/11 (9.1%) | 1 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 2/62 (3.2%) | 2 | 0/33 (0%) | 0 |
| Blood thyroid stimulating hormone decreased | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 1/13 (7.7%) | 1 | 0/12 (0%) | 0 | 1/12 (8.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/12 (8.3%) | 1 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 1/59 (1.7%) | 1 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Blood thyroid stimulating hormone increased | 1/13 (7.7%) | 1 | 0/12 (0%) | 0 | 1/11 (9.1%) | 1 | 0/13 (0%) | 0 | 2/12 (16.7%) | 2 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/12 (8.3%) | 1 | 1/12 (8.3%) | 1 | 0/7 (0%) | 0 | 3/59 (5.1%) | 3 | 0/62 (0%) | 0 | 1/33 (3%) | 1 |
| Blood urea increased | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 1/13 (7.7%) | 1 | 0/12 (0%) | 0 | 1/12 (8.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 1/59 (1.7%) | 1 | 1/62 (1.6%) | 1 | 0/33 (0%) | 0 |
| Electrocardiogram QT prolonged | 1/13 (7.7%) | 1 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/12 (8.3%) | 1 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Glycosylated haemoglobin increased | 1/13 (7.7%) | 1 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Haemoglobin decreased | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 1/11 (9.1%) | 1 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 3/59 (5.1%) | 3 | 0/62 (0%) | 0 | 2/33 (6.1%) | 2 |
| Lymphocyte count decreased | 1/13 (7.7%) | 1 | 0/12 (0%) | 0 | 1/11 (9.1%) | 1 | 1/13 (7.7%) | 1 | 1/12 (8.3%) | 2 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 1/12 (8.3%) | 1 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 5/59 (8.5%) | 7 | 3/62 (4.8%) | 5 | 2/33 (6.1%) | 2 |
| Neutrophil count decreased | 1/13 (7.7%) | 1 | 2/12 (16.7%) | 2 | 3/11 (27.3%) | 3 | 4/13 (30.8%) | 5 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 11/59 (18.6%) | 14 | 8/62 (12.9%) | 10 | 1/33 (3%) | 1 |
| Platelet count decreased | 1/13 (7.7%) | 1 | 1/12 (8.3%) | 1 | 3/11 (27.3%) | 3 | 2/13 (15.4%) | 3 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 3/59 (5.1%) | 4 | 8/62 (12.9%) | 11 | 2/33 (6.1%) | 2 |
| Thyroxine free decreased | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/12 (8.3%) | 1 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Thyroxine free increased | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 1/11 (9.1%) | 1 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 1/59 (1.7%) | 1 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Tri-iodothyronine decreased | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 1/13 (7.7%) | 1 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Weight decreased | 3/13 (23.1%) | 3 | 2/12 (16.7%) | 2 | 1/11 (9.1%) | 1 | 1/13 (7.7%) | 1 | 1/12 (8.3%) | 1 | 2/12 (16.7%) | 3 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/12 (8.3%) | 1 | 2/12 (16.7%) | 2 | 1/7 (14.3%) | 1 | 7/59 (11.9%) | 7 | 8/62 (12.9%) | 8 | 5/33 (15.2%) | 6 |
| Weight increased | 3/13 (23.1%) | 3 | 1/12 (8.3%) | 1 | 0/11 (0%) | 0 | 1/13 (7.7%) | 1 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 1/12 (8.3%) | 1 | 0/7 (0%) | 0 | 5/59 (8.5%) | 6 | 3/62 (4.8%) | 3 | 1/33 (3%) | 1 |
| White blood cell count decreased | 2/13 (15.4%) | 4 | 1/12 (8.3%) | 1 | 0/11 (0%) | 0 | 4/13 (30.8%) | 10 | 0/12 (0%) | 0 | 1/12 (8.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 6/59 (10.2%) | 8 | 8/62 (12.9%) | 13 | 0/33 (0%) | 0 |
| White blood cells urine positive | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 1/12 (8.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Metabolism and nutrition disorders | ||||||||||||||||||||||||||||
| Cachexia | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 1/7 (14.3%) | 1 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Decreased appetite | 7/13 (53.8%) | 8 | 5/12 (41.7%) | 5 | 2/11 (18.2%) | 2 | 6/13 (46.2%) | 6 | 4/12 (33.3%) | 4 | 5/12 (41.7%) | 7 | 2/3 (66.7%) | 2 | 1/3 (33.3%) | 1 | 4/12 (33.3%) | 5 | 2/12 (16.7%) | 2 | 1/7 (14.3%) | 1 | 19/59 (32.2%) | 25 | 15/62 (24.2%) | 19 | 7/33 (21.2%) | 7 |
| Dehydration | 2/13 (15.4%) | 2 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 2/13 (15.4%) | 2 | 2/12 (16.7%) | 2 | 1/12 (8.3%) | 1 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 2/12 (16.7%) | 2 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 4/59 (6.8%) | 5 | 4/62 (6.5%) | 4 | 1/33 (3%) | 1 |
| Glucose tolerance impaired | 1/13 (7.7%) | 1 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Gout | 1/13 (7.7%) | 2 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Hypercalcaemia | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 1/12 (8.3%) | 1 | 1/12 (8.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 1/59 (1.7%) | 1 | 4/62 (6.5%) | 4 | 0/33 (0%) | 0 |
| Hypercholesterolaemia | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 1/12 (8.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 1/62 (1.6%) | 1 | 0/33 (0%) | 0 |
| Hyperglycaemia | 2/13 (15.4%) | 3 | 0/12 (0%) | 0 | 3/11 (27.3%) | 3 | 2/13 (15.4%) | 2 | 0/12 (0%) | 0 | 1/12 (8.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 1/12 (8.3%) | 1 | 0/7 (0%) | 0 | 12/59 (20.3%) | 15 | 6/62 (9.7%) | 9 | 2/33 (6.1%) | 2 |
| Hyperkalaemia | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 1/11 (9.1%) | 3 | 1/13 (7.7%) | 1 | 2/12 (16.7%) | 2 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Hypernatraemia | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 1/12 (8.3%) | 1 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 2/59 (3.4%) | 2 | 1/62 (1.6%) | 1 | 0/33 (0%) | 0 |
| Hypertriglyceridaemia | 3/13 (23.1%) | 5 | 0/12 (0%) | 0 | 2/11 (18.2%) | 2 | 2/13 (15.4%) | 2 | 0/12 (0%) | 0 | 2/12 (16.7%) | 2 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 1/59 (1.7%) | 1 | 1/62 (1.6%) | 1 | 1/33 (3%) | 1 |
| Hyperuricaemia | 1/13 (7.7%) | 1 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Hypoalbuminaemia | 1/13 (7.7%) | 1 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 2/13 (15.4%) | 2 | 0/12 (0%) | 0 | 2/12 (16.7%) | 2 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 2/12 (16.7%) | 2 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 3/59 (5.1%) | 3 | 1/62 (1.6%) | 3 | 2/33 (6.1%) | 2 |
| Hypocalcaemia | 1/13 (7.7%) | 1 | 0/12 (0%) | 0 | 1/11 (9.1%) | 1 | 3/13 (23.1%) | 4 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 6/59 (10.2%) | 6 | 1/62 (1.6%) | 1 | 0/33 (0%) | 0 |
| Hypokalaemia | 2/13 (15.4%) | 3 | 1/12 (8.3%) | 1 | 0/11 (0%) | 0 | 1/13 (7.7%) | 2 | 1/12 (8.3%) | 1 | 1/12 (8.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 4/12 (33.3%) | 4 | 0/7 (0%) | 0 | 8/59 (13.6%) | 11 | 7/62 (11.3%) | 7 | 3/33 (9.1%) | 3 |
| Hypomagnesaemia | 2/13 (15.4%) | 2 | 1/12 (8.3%) | 1 | 1/11 (9.1%) | 1 | 4/13 (30.8%) | 4 | 2/12 (16.7%) | 2 | 2/12 (16.7%) | 2 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 1/12 (8.3%) | 1 | 1/12 (8.3%) | 1 | 0/7 (0%) | 0 | 4/59 (6.8%) | 4 | 3/62 (4.8%) | 4 | 3/33 (9.1%) | 3 |
| Hyponatraemia | 3/13 (23.1%) | 4 | 1/12 (8.3%) | 1 | 0/11 (0%) | 0 | 4/13 (30.8%) | 4 | 0/12 (0%) | 0 | 3/12 (25%) | 3 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 1/12 (8.3%) | 1 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 3/59 (5.1%) | 3 | 3/62 (4.8%) | 3 | 1/33 (3%) | 2 |
| Hypophosphataemia | 3/13 (23.1%) | 3 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 1/12 (8.3%) | 1 | 2/12 (16.7%) | 2 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/12 (8.3%) | 1 | 1/12 (8.3%) | 1 | 0/7 (0%) | 0 | 6/59 (10.2%) | 10 | 3/62 (4.8%) | 3 | 1/33 (3%) | 1 |
| Musculoskeletal and connective tissue disorders | ||||||||||||||||||||||||||||
| Arthralgia | 6/13 (46.2%) | 10 | 4/12 (33.3%) | 4 | 5/11 (45.5%) | 5 | 5/13 (38.5%) | 8 | 4/12 (33.3%) | 4 | 3/12 (25%) | 5 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 2/12 (16.7%) | 2 | 4/12 (33.3%) | 4 | 0/7 (0%) | 0 | 9/59 (15.3%) | 16 | 15/62 (24.2%) | 19 | 5/33 (15.2%) | 5 |
| Arthritis | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 1/11 (9.1%) | 1 | 0/13 (0%) | 0 | 1/12 (8.3%) | 1 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/12 (8.3%) | 1 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 1/59 (1.7%) | 1 | 1/62 (1.6%) | 1 | 0/33 (0%) | 0 |
| Back pain | 3/13 (23.1%) | 3 | 3/12 (25%) | 3 | 2/11 (18.2%) | 2 | 3/13 (23.1%) | 3 | 4/12 (33.3%) | 4 | 1/12 (8.3%) | 1 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 3/12 (25%) | 3 | 1/12 (8.3%) | 1 | 1/7 (14.3%) | 1 | 10/59 (16.9%) | 11 | 6/62 (9.7%) | 7 | 3/33 (9.1%) | 3 |
| Bone pain | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 1/11 (9.1%) | 1 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 1/59 (1.7%) | 1 | 2/62 (3.2%) | 2 | 1/33 (3%) | 1 |
| Connective tissue disorder | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 1/12 (8.3%) | 1 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Flank pain | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 1/12 (8.3%) | 1 | 1/7 (14.3%) | 1 | 1/59 (1.7%) | 1 | 1/62 (1.6%) | 1 | 0/33 (0%) | 0 |
| Foot deformity | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 1/13 (7.7%) | 1 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Groin pain | 0/13 (0%) | 0 | 1/12 (8.3%) | 1 | 1/11 (9.1%) | 1 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Joint range of motion decreased | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 1/12 (8.3%) | 1 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Joint swelling | 1/13 (7.7%) | 1 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 1/12 (8.3%) | 1 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 1/62 (1.6%) | 1 | 0/33 (0%) | 0 |
| Limb discomfort | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 1/12 (8.3%) | 1 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 3/59 (5.1%) | 3 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Mobility decreased | 0/13 (0%) | 0 | 1/12 (8.3%) | 1 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Muscle spasms | 1/13 (7.7%) | 1 | 3/12 (25%) | 4 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 1/12 (8.3%) | 1 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 3/12 (25%) | 4 | 0/7 (0%) | 0 | 2/59 (3.4%) | 5 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Muscular weakness | 1/13 (7.7%) | 1 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 1/59 (1.7%) | 1 | 2/62 (3.2%) | 2 | 0/33 (0%) | 0 |
| Musculoskeletal chest pain | 2/13 (15.4%) | 2 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 2/13 (15.4%) | 3 | 2/12 (16.7%) | 2 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 4/59 (6.8%) | 4 | 3/62 (4.8%) | 3 | 0/33 (0%) | 0 |
| Musculoskeletal discomfort | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 1/12 (8.3%) | 1 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 1/33 (3%) | 1 |
| Musculoskeletal pain | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 3/11 (27.3%) | 4 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 1/12 (8.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/12 (8.3%) | 1 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 9/59 (15.3%) | 10 | 4/62 (6.5%) | 4 | 3/33 (9.1%) | 3 |
| Musculoskeletal stiffness | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 1/12 (8.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 1/59 (1.7%) | 1 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Myalgia | 2/13 (15.4%) | 2 | 0/12 (0%) | 0 | 1/11 (9.1%) | 1 | 2/13 (15.4%) | 2 | 0/12 (0%) | 0 | 1/12 (8.3%) | 1 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 2/12 (16.7%) | 2 | 1/12 (8.3%) | 1 | 0/7 (0%) | 0 | 6/59 (10.2%) | 7 | 1/62 (1.6%) | 1 | 1/33 (3%) | 1 |
| Myalgia intercostal | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 1/12 (8.3%) | 1 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Neck pain | 1/13 (7.7%) | 1 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 1/13 (7.7%) | 1 | 1/12 (8.3%) | 1 | 2/12 (16.7%) | 2 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/12 (8.3%) | 2 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 3/59 (5.1%) | 3 | 4/62 (6.5%) | 4 | 1/33 (3%) | 1 |
| Pain in extremity | 3/13 (23.1%) | 3 | 3/12 (25%) | 5 | 4/11 (36.4%) | 5 | 2/13 (15.4%) | 2 | 2/12 (16.7%) | 3 | 3/12 (25%) | 3 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 8/59 (13.6%) | 9 | 3/62 (4.8%) | 5 | 4/33 (12.1%) | 4 |
| Pain in jaw | 1/13 (7.7%) | 1 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 1/62 (1.6%) | 1 | 0/33 (0%) | 0 |
| Periarthritis | 1/13 (7.7%) | 1 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Spinal column stenosis | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 1/13 (7.7%) | 1 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Spinal osteoarthritis | 0/13 (0%) | 0 | 1/12 (8.3%) | 1 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Synovial cyst | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 1/12 (8.3%) | 1 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Tendonitis | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||||||||||||||||||||||
| Cancer pain | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 1/12 (8.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/12 (8.3%) | 1 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Corneoconjunctival intraepithelial neoplasia | 1/13 (7.7%) | 1 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Nervous system disorders | ||||||||||||||||||||||||||||
| Ageusia | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 1/12 (8.3%) | 1 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Balance disorder | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 1/12 (8.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 1/62 (1.6%) | 1 | 1/33 (3%) | 1 |
| Cognitive disorder | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 1/12 (8.3%) | 1 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 2/59 (3.4%) | 5 | 0/62 (0%) | 0 | 1/33 (3%) | 1 |
| Dizziness | 2/13 (15.4%) | 2 | 2/12 (16.7%) | 2 | 1/11 (9.1%) | 1 | 1/13 (7.7%) | 2 | 3/12 (25%) | 3 | 4/12 (33.3%) | 4 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 2/12 (16.7%) | 2 | 6/12 (50%) | 6 | 0/7 (0%) | 0 | 14/59 (23.7%) | 17 | 10/62 (16.1%) | 13 | 3/33 (9.1%) | 3 |
| Dizziness postural | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 1/13 (7.7%) | 1 | 0/12 (0%) | 0 | 1/12 (8.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 1/59 (1.7%) | 1 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Dysarthria | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 1/11 (9.1%) | 1 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Dysgeusia | 3/13 (23.1%) | 3 | 3/12 (25%) | 4 | 3/11 (27.3%) | 3 | 2/13 (15.4%) | 2 | 1/12 (8.3%) | 1 | 1/12 (8.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 3/12 (25%) | 3 | 0/7 (0%) | 0 | 12/59 (20.3%) | 19 | 7/62 (11.3%) | 9 | 0/33 (0%) | 0 |
| Head titubation | 1/13 (7.7%) | 1 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Headache | 3/13 (23.1%) | 3 | 1/12 (8.3%) | 1 | 4/11 (36.4%) | 4 | 2/13 (15.4%) | 2 | 3/12 (25%) | 3 | 2/12 (16.7%) | 2 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/12 (8.3%) | 1 | 2/12 (16.7%) | 4 | 1/7 (14.3%) | 1 | 18/59 (30.5%) | 23 | 10/62 (16.1%) | 10 | 6/33 (18.2%) | 6 |
| Hypoaesthesia | 1/13 (7.7%) | 1 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 1/13 (7.7%) | 1 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 2/59 (3.4%) | 3 | 1/62 (1.6%) | 1 | 1/33 (3%) | 1 |
| Hypogeusia | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 1/11 (9.1%) | 1 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Memory impairment | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 1/12 (8.3%) | 1 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 3/59 (5.1%) | 3 | 1/62 (1.6%) | 1 | 0/33 (0%) | 0 |
| Myasthenia gravis | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/12 (8.3%) | 1 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Neuropathy peripheral | 5/13 (38.5%) | 5 | 3/12 (25%) | 3 | 2/11 (18.2%) | 2 | 3/13 (23.1%) | 4 | 3/12 (25%) | 3 | 3/12 (25%) | 4 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/12 (8.3%) | 1 | 4/12 (33.3%) | 4 | 0/7 (0%) | 0 | 8/59 (13.6%) | 9 | 3/62 (4.8%) | 4 | 4/33 (12.1%) | 4 |
| Neurotoxicity | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 1/13 (7.7%) | 1 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Paraesthesia | 0/13 (0%) | 0 | 1/12 (8.3%) | 1 | 3/11 (27.3%) | 3 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 3/59 (5.1%) | 3 | 2/62 (3.2%) | 2 | 0/33 (0%) | 0 |
| Peripheral motor neuropathy | 1/13 (7.7%) | 1 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 2/59 (3.4%) | 2 | 0/62 (0%) | 0 | 1/33 (3%) | 1 |
| Peripheral sensory neuropathy | 3/13 (23.1%) | 3 | 3/12 (25%) | 3 | 5/11 (45.5%) | 5 | 3/13 (23.1%) | 3 | 1/12 (8.3%) | 1 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 2/59 (3.4%) | 2 | 4/62 (6.5%) | 4 | 1/33 (3%) | 1 |
| Post herpetic neuralgia | 1/13 (7.7%) | 3 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 1/59 (1.7%) | 1 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Seizure | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 1/11 (9.1%) | 1 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Sinus headache | 1/13 (7.7%) | 1 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Somnolence | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 1/12 (8.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 1/33 (3%) | 1 |
| Syncope | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 1/12 (8.3%) | 2 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 2/12 (16.7%) | 2 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 4/59 (6.8%) | 5 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Tremor | 1/13 (7.7%) | 1 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 1/62 (1.6%) | 1 | 1/33 (3%) | 1 |
| Vocal cord paralysis | 1/13 (7.7%) | 1 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Psychiatric disorders | ||||||||||||||||||||||||||||
| Anxiety | 0/13 (0%) | 0 | 1/12 (8.3%) | 1 | 2/11 (18.2%) | 2 | 1/13 (7.7%) | 1 | 4/12 (33.3%) | 4 | 1/12 (8.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/12 (8.3%) | 1 | 1/12 (8.3%) | 1 | 0/7 (0%) | 0 | 6/59 (10.2%) | 7 | 3/62 (4.8%) | 3 | 3/33 (9.1%) | 3 |
| Confusional state | 2/13 (15.4%) | 2 | 0/12 (0%) | 0 | 2/11 (18.2%) | 2 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 1/59 (1.7%) | 1 | 1/62 (1.6%) | 1 | 1/33 (3%) | 1 |
| Depressed mood | 1/13 (7.7%) | 1 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 1/33 (3%) | 1 |
| Depression | 3/13 (23.1%) | 3 | 1/12 (8.3%) | 1 | 1/11 (9.1%) | 1 | 0/13 (0%) | 0 | 2/12 (16.7%) | 2 | 1/12 (8.3%) | 1 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 2/12 (16.7%) | 2 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 2/59 (3.4%) | 2 | 7/62 (11.3%) | 7 | 1/33 (3%) | 1 |
| Emotional poverty | 1/13 (7.7%) | 1 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Insomnia | 2/13 (15.4%) | 2 | 0/12 (0%) | 0 | 2/11 (18.2%) | 2 | 3/13 (23.1%) | 3 | 2/12 (16.7%) | 2 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/12 (8.3%) | 1 | 1/12 (8.3%) | 1 | 0/7 (0%) | 0 | 15/59 (25.4%) | 20 | 9/62 (14.5%) | 11 | 2/33 (6.1%) | 2 |
| Irritability | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 1/12 (8.3%) | 1 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Libido decreased | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 1/12 (8.3%) | 1 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 1/59 (1.7%) | 1 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Personality change | 1/13 (7.7%) | 1 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 1/12 (8.3%) | 1 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Renal and urinary disorders | ||||||||||||||||||||||||||||
| Acute kidney injury | 1/13 (7.7%) | 1 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 1/12 (8.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 2/59 (3.4%) | 2 | 1/62 (1.6%) | 1 | 0/33 (0%) | 0 |
| Bladder prolapse | 0/13 (0%) | 0 | 1/12 (8.3%) | 1 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Dysuria | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 1/11 (9.1%) | 2 | 0/13 (0%) | 0 | 1/12 (8.3%) | 1 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/12 (0%) | 0 | 1/12 (8.3%) | 1 | 0/7 (0%) | 0 | 3/59 (5.1%) | 3 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Haematuria | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 3/11 (27.3%) | 3 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 1/12 (8.3%) | 1 | 1/7 (14.3%) | 1 | 3/59 (5.1%) | 3 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Incontinence | 1/13 (7.7%) | 1 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Nephrolithiasis | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 1/12 (8.3%) | 1 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Nocturia | 1/13 (7.7%) | 1 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Pollakiuria | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 1/13 (7.7%) | 1 | 0/12 (0%) | 0 | 1/12 (8.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 4/59 (6.8%) | 4 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Proteinuria | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 2/11 (18.2%) | 2 | 2/13 (15.4%) | 2 | 1/12 (8.3%) | 1 | 2/12 (16.7%) | 2 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 1/59 (1.7%) | 1 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Renal disorder | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 1/12 (8.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Renal pain | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 1/12 (8.3%) | 1 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Urinary incontinence | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 1/62 (1.6%) | 1 | 0/33 (0%) | 0 |
| Urine flow decreased | 1/13 (7.7%) | 1 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Reproductive system and breast disorders | ||||||||||||||||||||||||||||
| Menstruation irregular | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 1/12 (8.3%) | 1 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 1/62 (1.6%) | 1 | 0/33 (0%) | 0 |
| Respiratory, thoracic and mediastinal disorders | ||||||||||||||||||||||||||||
| Bronchial obstruction | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 1/12 (8.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Chronic obstructive pulmonary disease | 1/13 (7.7%) | 2 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 1/12 (8.3%) | 1 | 1/12 (8.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/12 (8.3%) | 1 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 1/59 (1.7%) | 1 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Cough | 7/13 (53.8%) | 11 | 3/12 (25%) | 3 | 3/11 (27.3%) | 4 | 7/13 (53.8%) | 8 | 4/12 (33.3%) | 4 | 5/12 (41.7%) | 6 | 2/3 (66.7%) | 2 | 0/3 (0%) | 0 | 4/12 (33.3%) | 4 | 6/12 (50%) | 8 | 1/7 (14.3%) | 1 | 16/59 (27.1%) | 21 | 13/62 (21%) | 16 | 6/33 (18.2%) | 7 |
| Dysphonia | 4/13 (30.8%) | 5 | 1/12 (8.3%) | 2 | 1/11 (9.1%) | 1 | 1/13 (7.7%) | 1 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 7/59 (11.9%) | 7 | 5/62 (8.1%) | 5 | 3/33 (9.1%) | 4 |
| Dyspnoea | 4/13 (30.8%) | 4 | 1/12 (8.3%) | 1 | 2/11 (18.2%) | 2 | 3/13 (23.1%) | 3 | 3/12 (25%) | 3 | 3/12 (25%) | 4 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 3/12 (25%) | 3 | 3/12 (25%) | 4 | 0/7 (0%) | 0 | 23/59 (39%) | 26 | 13/62 (21%) | 15 | 8/33 (24.2%) | 10 |
| Dyspnoea exertional | 1/13 (7.7%) | 1 | 1/12 (8.3%) | 1 | 1/11 (9.1%) | 1 | 1/13 (7.7%) | 1 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 1/59 (1.7%) | 1 | 3/62 (4.8%) | 3 | 1/33 (3%) | 1 |
| Epistaxis | 1/13 (7.7%) | 1 | 0/12 (0%) | 0 | 4/11 (36.4%) | 4 | 4/13 (30.8%) | 4 | 2/12 (16.7%) | 2 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 1/12 (8.3%) | 1 | 0/7 (0%) | 0 | 3/59 (5.1%) | 4 | 3/62 (4.8%) | 4 | 0/33 (0%) | 0 |
| Haemoptysis | 0/13 (0%) | 0 | 1/12 (8.3%) | 1 | 2/11 (18.2%) | 3 | 1/13 (7.7%) | 1 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 2/59 (3.4%) | 2 | 1/62 (1.6%) | 1 | 1/33 (3%) | 2 |
| Hiccups | 1/13 (7.7%) | 1 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 1/59 (1.7%) | 1 | 2/62 (3.2%) | 2 | 0/33 (0%) | 0 |
| Hypoxia | 1/13 (7.7%) | 1 | 0/12 (0%) | 0 | 1/11 (9.1%) | 1 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 1/62 (1.6%) | 1 | 2/33 (6.1%) | 2 |
| Interstitial lung disease | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 1/7 (14.3%) | 1 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Nasal congestion | 2/13 (15.4%) | 2 | 4/12 (33.3%) | 4 | 0/11 (0%) | 0 | 3/13 (23.1%) | 4 | 0/12 (0%) | 0 | 3/12 (25%) | 4 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 2/12 (16.7%) | 2 | 2/12 (16.7%) | 2 | 0/7 (0%) | 0 | 5/59 (8.5%) | 7 | 2/62 (3.2%) | 2 | 2/33 (6.1%) | 2 |
| Nasal dryness | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 1/11 (9.1%) | 1 | 1/13 (7.7%) | 1 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 1/59 (1.7%) | 1 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Oropharyngeal discomfort | 1/13 (7.7%) | 1 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Oropharyngeal pain | 0/13 (0%) | 0 | 1/12 (8.3%) | 1 | 1/11 (9.1%) | 1 | 2/13 (15.4%) | 2 | 1/12 (8.3%) | 1 | 1/12 (8.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/12 (8.3%) | 1 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 2/59 (3.4%) | 2 | 4/62 (6.5%) | 4 | 0/33 (0%) | 0 |
| Paranasal sinus discomfort | 1/13 (7.7%) | 1 | 0/12 (0%) | 0 | 1/11 (9.1%) | 1 | 0/13 (0%) | 0 | 1/12 (8.3%) | 1 | 2/12 (16.7%) | 2 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Paranasal sinus hypersecretion | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 1/12 (8.3%) | 1 | 1/12 (8.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 1/12 (8.3%) | 1 | 0/7 (0%) | 0 | 1/59 (1.7%) | 1 | 1/62 (1.6%) | 1 | 0/33 (0%) | 0 |
| Pleural effusion | 1/13 (7.7%) | 1 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 1/12 (8.3%) | 1 | 1/12 (8.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 2/12 (16.7%) | 2 | 0/7 (0%) | 0 | 2/59 (3.4%) | 2 | 0/62 (0%) | 0 | 2/33 (6.1%) | 2 |
| Pneumonitis | 1/13 (7.7%) | 1 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 3/59 (5.1%) | 3 | 0/62 (0%) | 0 | 1/33 (3%) | 1 |
| Pneumothorax | 1/13 (7.7%) | 2 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Productive cough | 1/13 (7.7%) | 1 | 0/12 (0%) | 0 | 1/11 (9.1%) | 1 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 1/12 (8.3%) | 1 | 0/7 (0%) | 0 | 2/59 (3.4%) | 2 | 1/62 (1.6%) | 1 | 1/33 (3%) | 1 |
| Pulmonary oedema | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 1/12 (8.3%) | 1 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Pulmonary pain | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 1/11 (9.1%) | 1 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Respiratory tract congestion | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 1/12 (8.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 1/59 (1.7%) | 1 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Rhinalgia | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 1/12 (8.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Rhinitis allergic | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 1/12 (8.3%) | 1 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/12 (0%) | 0 | 2/12 (16.7%) | 2 | 0/7 (0%) | 0 | 2/59 (3.4%) | 3 | 3/62 (4.8%) | 3 | 0/33 (0%) | 0 |
| Rhinorrhoea | 1/13 (7.7%) | 2 | 2/12 (16.7%) | 2 | 1/11 (9.1%) | 1 | 4/13 (30.8%) | 4 | 4/12 (33.3%) | 4 | 2/12 (16.7%) | 2 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 1/12 (8.3%) | 1 | 0/7 (0%) | 0 | 6/59 (10.2%) | 6 | 4/62 (6.5%) | 4 | 2/33 (6.1%) | 2 |
| Sinus congestion | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 1/11 (9.1%) | 1 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 2/12 (16.7%) | 2 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/12 (8.3%) | 1 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 1/62 (1.6%) | 1 | 0/33 (0%) | 0 |
| Sneezing | 1/13 (7.7%) | 1 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Sputum increased | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/12 (8.3%) | 1 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Upper respiratory tract congestion | 0/13 (0%) | 0 | 1/12 (8.3%) | 1 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Upper-airway cough syndrome | 1/13 (7.7%) | 1 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 4/59 (6.8%) | 4 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Wheezing | 1/13 (7.7%) | 1 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 1/12 (8.3%) | 1 | 1/12 (8.3%) | 3 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 1/12 (8.3%) | 1 | 0/7 (0%) | 0 | 3/59 (5.1%) | 3 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Skin and subcutaneous tissue disorders | ||||||||||||||||||||||||||||
| Acne cystic | 1/13 (7.7%) | 1 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Actinic keratosis | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Alopecia | 7/13 (53.8%) | 7 | 7/12 (58.3%) | 7 | 8/11 (72.7%) | 8 | 8/13 (61.5%) | 8 | 0/12 (0%) | 0 | 2/12 (16.7%) | 2 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 3/12 (25%) | 3 | 0/7 (0%) | 0 | 12/59 (20.3%) | 13 | 2/62 (3.2%) | 2 | 0/33 (0%) | 0 |
| Alopecia areata | 1/13 (7.7%) | 1 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Cold sweat | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/12 (8.3%) | 1 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 1/62 (1.6%) | 1 | 0/33 (0%) | 0 |
| Dermatitis acneiform | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 5/12 (41.7%) | 7 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Drug eruption | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/12 (8.3%) | 2 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Dry skin | 2/13 (15.4%) | 3 | 1/12 (8.3%) | 1 | 1/11 (9.1%) | 1 | 2/13 (15.4%) | 3 | 2/12 (16.7%) | 2 | 4/12 (33.3%) | 4 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/12 (8.3%) | 1 | 3/12 (25%) | 3 | 0/7 (0%) | 0 | 3/59 (5.1%) | 3 | 4/62 (6.5%) | 4 | 2/33 (6.1%) | 2 |
| Eczema | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 1/13 (7.7%) | 1 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 1/12 (8.3%) | 3 | 1/7 (14.3%) | 1 | 1/59 (1.7%) | 1 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Erythema | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 2/13 (15.4%) | 2 | 0/12 (0%) | 0 | 1/12 (8.3%) | 2 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 2/59 (3.4%) | 2 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Hair colour changes | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 1/12 (8.3%) | 1 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Hyperhidrosis | 1/13 (7.7%) | 1 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 3/59 (5.1%) | 4 | 0/62 (0%) | 0 | 1/33 (3%) | 1 |
| Ingrowing nail | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 2/12 (16.7%) | 2 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Ingrown hair | 1/13 (7.7%) | 1 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 1/59 (1.7%) | 1 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Lichenoid keratosis | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 1/12 (8.3%) | 1 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Macule | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 1/12 (8.3%) | 1 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Nail bed disorder | 1/13 (7.7%) | 1 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Nail discolouration | 2/13 (15.4%) | 2 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 1/59 (1.7%) | 1 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Nail disorder | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 1/12 (8.3%) | 1 | 0/7 (0%) | 0 | 1/59 (1.7%) | 1 | 1/62 (1.6%) | 1 | 0/33 (0%) | 0 |
| Nail ridging | 1/13 (7.7%) | 1 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Night sweats | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 1/12 (8.3%) | 1 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 1/12 (8.3%) | 1 | 0/7 (0%) | 0 | 1/59 (1.7%) | 1 | 2/62 (3.2%) | 2 | 0/33 (0%) | 0 |
| Papule | 0/13 (0%) | 0 | 1/12 (8.3%) | 1 | 1/11 (9.1%) | 1 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 1/33 (3%) | 1 |
| Petechiae | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 1/12 (8.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 1/62 (1.6%) | 1 | 0/33 (0%) | 0 |
| Pruritus | 3/13 (23.1%) | 3 | 1/12 (8.3%) | 1 | 1/11 (9.1%) | 1 | 2/13 (15.4%) | 2 | 2/12 (16.7%) | 2 | 5/12 (41.7%) | 6 | 0/3 (0%) | 0 | 1/3 (33.3%) | 2 | 3/12 (25%) | 4 | 5/12 (41.7%) | 5 | 2/7 (28.6%) | 2 | 15/59 (25.4%) | 19 | 3/62 (4.8%) | 4 | 4/33 (12.1%) | 5 |
| Pruritus generalised | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/12 (8.3%) | 1 | 0/12 (0%) | 0 | 1/7 (14.3%) | 1 | 0/59 (0%) | 0 | 1/62 (1.6%) | 1 | 0/33 (0%) | 0 |
| Purpura | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/12 (8.3%) | 1 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 1/59 (1.7%) | 1 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Rash | 4/13 (30.8%) | 5 | 2/12 (16.7%) | 2 | 3/11 (27.3%) | 3 | 5/13 (38.5%) | 6 | 3/12 (25%) | 4 | 4/12 (33.3%) | 5 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 3/12 (25%) | 4 | 6/12 (50%) | 16 | 2/7 (28.6%) | 2 | 19/59 (32.2%) | 29 | 10/62 (16.1%) | 12 | 2/33 (6.1%) | 3 |
| Rash erythematous | 1/13 (7.7%) | 1 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Rash generalised | 1/13 (7.7%) | 1 | 1/12 (8.3%) | 1 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 1/62 (1.6%) | 1 | 0/33 (0%) | 0 |
| Rash macular | 1/13 (7.7%) | 1 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 1/12 (8.3%) | 1 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 1/62 (1.6%) | 1 | 0/33 (0%) | 0 |
| Rash maculo-papular | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 1/11 (9.1%) | 1 | 1/13 (7.7%) | 1 | 4/12 (33.3%) | 4 | 2/12 (16.7%) | 2 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 2/12 (16.7%) | 4 | 3/12 (25%) | 4 | 0/7 (0%) | 0 | 6/59 (10.2%) | 6 | 2/62 (3.2%) | 2 | 1/33 (3%) | 2 |
| Rash papular | 0/13 (0%) | 0 | 1/12 (8.3%) | 1 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Rash pruritic | 1/13 (7.7%) | 1 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 1/59 (1.7%) | 1 | 0/62 (0%) | 0 | 1/33 (3%) | 1 |
| Rosacea | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 1/13 (7.7%) | 1 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 1/62 (1.6%) | 1 | 0/33 (0%) | 0 |
| Scab | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 1/12 (8.3%) | 1 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Seborrhoeic dermatitis | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 1/13 (7.7%) | 1 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Skin discolouration | 1/13 (7.7%) | 1 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 1/12 (8.3%) | 1 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 1/12 (8.3%) | 1 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Skin erosion | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 1/12 (8.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Skin exfoliation | 0/13 (0%) | 0 | 1/12 (8.3%) | 1 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/12 (8.3%) | 1 | 2/12 (16.7%) | 2 | 1/7 (14.3%) | 1 | 2/59 (3.4%) | 2 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Skin fissures | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 1/7 (14.3%) | 1 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Skin hyperpigmentation | 0/13 (0%) | 0 | 1/12 (8.3%) | 1 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Skin hypopigmentation | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 1/12 (8.3%) | 1 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Skin irritation | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 1/12 (8.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Skin lesion | 1/13 (7.7%) | 1 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 1/62 (1.6%) | 1 | 0/33 (0%) | 0 |
| Skin mass | 0/13 (0%) | 0 | 1/12 (8.3%) | 1 | 1/11 (9.1%) | 1 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Skin ulcer | 1/13 (7.7%) | 1 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 1/33 (3%) | 1 |
| Urticaria | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 1/12 (8.3%) | 1 | 0/7 (0%) | 0 | 2/59 (3.4%) | 2 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Vascular disorders | ||||||||||||||||||||||||||||
| Deep vein thrombosis | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 1/12 (8.3%) | 2 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 2/62 (3.2%) | 2 | 1/33 (3%) | 1 |
| Flushing | 1/13 (7.7%) | 2 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 1/13 (7.7%) | 1 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 5/59 (8.5%) | 5 | 2/62 (3.2%) | 2 | 2/33 (6.1%) | 2 |
| Hypertension | 0/13 (0%) | 0 | 2/12 (16.7%) | 2 | 0/11 (0%) | 0 | 2/13 (15.4%) | 2 | 3/12 (25%) | 3 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 8/59 (13.6%) | 11 | 3/62 (4.8%) | 3 | 1/33 (3%) | 1 |
| Hypotension | 1/13 (7.7%) | 1 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 1/13 (7.7%) | 1 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/12 (8.3%) | 1 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 2/59 (3.4%) | 3 | 2/62 (3.2%) | 2 | 0/33 (0%) | 0 |
| Pelvic venous thrombosis | 0/13 (0%) | 0 | 1/12 (8.3%) | 1 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Phlebitis | 2/13 (15.4%) | 3 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 1/13 (7.7%) | 1 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 1/62 (1.6%) | 1 | 0/33 (0%) | 0 |
| Poor venous access | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 1/13 (7.7%) | 1 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Thrombophlebitis | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 1/11 (9.1%) | 1 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
| Venous thrombosis | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/13 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 1/12 (8.3%) | 1 | 0/7 (0%) | 0 | 0/59 (0%) | 0 | 0/62 (0%) | 0 | 0/33 (0%) | 0 |
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The Sponsor must have the opportunity to review all proposed abstracts, manuscripts or presentations regarding this study 45 days prior to submission for publication/presentation. Any information identified by the Sponsor as confidential must be deleted prior to submission; this confidentiality does not include efficacy and safety results.
Results Point of Contact
| Name/Title | Senior Vice President, Global Clinical Development |
|---|---|
| Organization | Merck Sharp & Dohme Corp. |
| Phone | 1-800-672-6372 |
| ClinicalTrialsDisclosure@merck.com |
Responsible Party:
Merck Sharp & Dohme LLC
ClinicalTrials.gov Identifier:
NCT02039674
Other Study ID Numbers:
- 3475-021
- MK-3475-021
- KEYNOTE-021
First Posted:
Jan 17, 2014
Last Update Posted:
Nov 3, 2021
Last Verified:
Oct 1, 2021