A Dose Escalation Study of MK-1775 in Combination With Either Gemcitabine, Cisplatin, or Carboplatin in Adults With Advanced Solid Tumors (MK-1775-001)
Sponsor
Merck Sharp & Dohme LLC (Industry)
Overall Status
Completed
CT.gov ID
NCT00648648
Collaborator
(none)
206
28
70.4
Study Details
Study Description
Brief Summary
This study will investigate the safety, tolerability, pharmacokinetic (PK), and pharmacodynamic (PD) activity of MK-1775, both as monotherapy and in combination with gemcitabine, cisplatin, or carboplatin in participants with advanced solid tumors. Dose limiting toxicities (DLT) of MK-1775 in combination with gemcitabine, cisplatin, or carboplatin will also be assessed. The primary hypotheses of the study are as follows: 1) Oral administration of MK-1775 both as monotherapy and in combination with either gemcitabine, cisplatin, or carboplatin in patients with advanced solid tumors will be safe and tolerable, 2) The side effects observed in participants with advanced solid tumors after administration of MK-1775 combined with each of the chemotherapies (gemcitabine, cisplatin and carboplatin) will allow for the definition of a single dose combination Maximum Administered Dose (MAD)/Maximum Tolerated Dose (MTD) and a multiple dose combination Biologically Effective Dose (BED)/MTD for each of the 3 combinations, 3) At a tolerated dose, MK-1775 plasma exposure will exceed target thresholds established in preclinical models, and 4) At a tolerated dose, PD markers of MK-1775 activity in combination with either gemcitabine, cisplatin, or carboplatin (in surrogate tissue and/or tumor) will meet or exceed the target threshold established in preclinical models.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1 |
Detailed Description
Part 1 consists of single dose MK-1775 monotherapy. If well tolerated, participants in Part 1 will continue on to one of three treatment arms in Part 2-A which consists of a single lower dose of MK-1775 in combination with standard chemotherapy: 1) MK-1775 +Gemcitabine (1000 mg/m2), 2) MK-1775 + Cisplatin (75 mg/m2) or 3) MK-1775 +Carboplatin at an area under the time curve concentration of 5 mg/min/ml (AUC5). Following completion of Part 2-A, MK-1775 will be administered twice daily (BID) for 2.5 days (multi-dose) starting concomitantly with each administration of chemotherapy in Part 2-B. After a preliminary combination MTD of MK-1775 and chemotherapy has been established in Part 2B, the MTD confirmation expansion will occur in Part 3.
Study Design
Study Type:
Interventional
Actual Enrollment
:
206 participants
Allocation:
Non-Randomized
Intervention Model:
Sequential Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase I Dose Escalation Study Evaluating MK-1775 in Both Monotherapy and in Combination With Either Gemcitabine, Cisplatin, or Carboplatin in Adult Subjects With Advanced Solid Tumors
Actual Study Start Date
:
Feb 25, 2008
Actual Primary Completion Date
:
Jan 6, 2014
Actual Study Completion Date
:
Jan 6, 2014
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: MK-1775 325 mg Single Dose Participants received MK-1775 325 mg, orally, on Day 1. |
Drug: MK-1775
MK-1775 administered as an oral formulation as either monotherapy or in combination with either gemcitabine, cisplatin, or carboplatin.
|
| Experimental: MK-1775 650 mg Single Dose Participants received MK-1775 650 mg, orally, on Day 1. |
Drug: MK-1775
MK-1775 administered as an oral formulation as either monotherapy or in combination with either gemcitabine, cisplatin, or carboplatin.
|
| Experimental: MK-1775 1300 mg Single Dose Participants received MK-1775 1300 mg, orally, on Day 1. |
Drug: MK-1775
MK-1775 administered as an oral formulation as either monotherapy or in combination with either gemcitabine, cisplatin, or carboplatin.
|
| Experimental: MK-1775 100 mg Single Dose + Gemcitabine 1000 mg/m^2 Participants received gemcitabine 1000 mg/m^2 as an intravenous (IV) infusion on Days 1, 8, and 15 in each 4-week cycle plus MK-1775 100 mg single dose, orally, on Day 2 of each cycle. |
Drug: MK-1775
MK-1775 administered as an oral formulation as either monotherapy or in combination with either gemcitabine, cisplatin, or carboplatin.
Drug: gemcitabine
Gemcitabine administered at 1000 mg/m^2 by IV infusion in a 28-day cycle.
|
| Experimental: MK-1775 200 mg Single Dose + Gemcitabine 1000 mg/m^2 Participants received gemcitabine 1000 mg/m^2 as an IV infusion on Days 1, 8, and 15 in each 4-week cycle plus MK-1775 200 mg single dose, orally, on Day 2 of each cycle. |
Drug: MK-1775
MK-1775 administered as an oral formulation as either monotherapy or in combination with either gemcitabine, cisplatin, or carboplatin.
Drug: gemcitabine
Gemcitabine administered at 1000 mg/m^2 by IV infusion in a 28-day cycle.
|
| Experimental: MK-1775 100 mg Single Dose + Cisplatin 75 mg/ m^2 Participants received cisplatin 75 mg/ m^2 as an IV infusion on Day 1 of each 3 week cycle plus MK-1775 100 mg single dose orally, on Day 2 of each cycle. |
Drug: MK-1775
MK-1775 administered as an oral formulation as either monotherapy or in combination with either gemcitabine, cisplatin, or carboplatin.
Drug: cisplatin
Cisplatin administered at 75 mg/m^2 by IV infusion in a 21-day cycle.
|
| Experimental: MK-1775 200 mg Single Dose + Cisplatin 75 mg/ m^2 Participants received cisplatin 75 mg/ m^2 as an IV infusion on Day 1 of each 3 week cycle plus MK-1775 200 mg single dose orally, on Day 2 of each cycle. |
Drug: MK-1775
MK-1775 administered as an oral formulation as either monotherapy or in combination with either gemcitabine, cisplatin, or carboplatin.
Drug: cisplatin
Cisplatin administered at 75 mg/m^2 by IV infusion in a 21-day cycle.
|
| Experimental: MK-1775 100 mg Single Dose + Carboplatin AUC 5 Participants received carboplatin at an area under the time curve concentration of 5 mg/min/ml (AUC5) as an IV infusion on Day 1 of each 3 week cycle plus MK-1775 100 mg single dose orally, on Day 2 of each cycle. |
Drug: MK-1775
MK-1775 administered as an oral formulation as either monotherapy or in combination with either gemcitabine, cisplatin, or carboplatin.
Drug: carboplatin
Carboplatin administered at AUC/time curve of 5 mg/min/mL (AUC5) by IV infusion in a 21-day cycle.
|
| Experimental: MK-1775 200 mg Single Dose + Carboplatin AUC 5 Participants received carboplatin AUC5 as an IV infusion on Day 1 of each 3 week cycle plus MK-1775 200 mg single dose orally, on Day 2 of each cycle. |
Drug: MK-1775
MK-1775 administered as an oral formulation as either monotherapy or in combination with either gemcitabine, cisplatin, or carboplatin.
Drug: carboplatin
Carboplatin administered at AUC/time curve of 5 mg/min/mL (AUC5) by IV infusion in a 21-day cycle.
|
| Experimental: MK-1775 325 mg Single Dose + Carboplatin AUC 5 Participants received carboplatin AUC5 as an IV infusion on Day 1 of each 3 week cycle plus MK-1775 325 mg single dose orally, on Day 2 of each cycle. |
Drug: MK-1775
MK-1775 administered as an oral formulation as either monotherapy or in combination with either gemcitabine, cisplatin, or carboplatin.
Drug: carboplatin
Carboplatin administered at AUC/time curve of 5 mg/min/mL (AUC5) by IV infusion in a 21-day cycle.
|
| Experimental: MK-1775 25 mg BID x2.5 Multi Dose + Gemcitabine 1000 mg/ m^2 Participants received gemcitabine 1000 mg/m^2 as an IV infusion on Days 1, 8, and 15 of each 4-week cycle plus MK-1775 25 mg orally twice daily (BID) for 2.5 days, starting concomitantly with the IV infusion of gemcitabine on Day 1 and followed by 4 additional doses of MK-1775 25 mg at approximately 12 hour intervals on Days 1-3, 8-9, and 15-17 of each cycle. |
Drug: MK-1775
MK-1775 administered as an oral formulation as either monotherapy or in combination with either gemcitabine, cisplatin, or carboplatin.
Drug: gemcitabine
Gemcitabine administered at 1000 mg/m^2 by IV infusion in a 28-day cycle.
|
| Experimental: MK-1775 50/25 mg BID x2.5 Multi + Gemcitabine 1000 mg/ m^2 Participants received gemcitabine 1000 mg/m^2 as an IV infusion on Days 1, 8, and 15 of each 4 week cycle plus MK-1775 50 mg orally BID for 2.5 days, starting concomitantly with the IV infusion of gemcitabine on Day 1 and followed by 4 doses of MK-1775 25 mg at approximately 12 hour intervals on Days 1-3, 8-9, and 15-17 of each 4 week cycle. |
Drug: MK-1775
MK-1775 administered as an oral formulation as either monotherapy or in combination with either gemcitabine, cisplatin, or carboplatin.
Drug: gemcitabine
Gemcitabine administered at 1000 mg/m^2 by IV infusion in a 28-day cycle.
|
| Experimental: MK-1775 50 mg BID x2.5 Multi + Gemcitabine 1000 mg/ m^2 Participants received gemcitabine 1000 mg/m^2 as an IV infusion given once weekly for 3 consecutive weeks of a 4 week cycle plus MK-1775 50 mg orally BID for 2.5 days, starting concomitantly with the IV infusion of gemcitabine on Day 1 and followed by 4 additional doses of MK-1775 50 mg at approximately 12 hour intervals on Days 1-3, 8-9, and 15-17 of each 4 week cycle. |
Drug: MK-1775
MK-1775 administered as an oral formulation as either monotherapy or in combination with either gemcitabine, cisplatin, or carboplatin.
Drug: gemcitabine
Gemcitabine administered at 1000 mg/m^2 by IV infusion in a 28-day cycle.
|
| Experimental: MK-1775 100 mg QD x2 Multi + Gemcitabine 1000 mg/ m^2 Participants received gemcitabine 1000 mg/m^2 as an IV infusion on Days 1, 8, and 15 of each 4 week cycle plus MK-1775 100 mg orally once daily (QD) on Days 1, 2, 8, 9, 15, and 16 of each 4 week cycle. |
Drug: MK-1775
MK-1775 administered as an oral formulation as either monotherapy or in combination with either gemcitabine, cisplatin, or carboplatin.
Drug: gemcitabine
Gemcitabine administered at 1000 mg/m^2 by IV infusion in a 28-day cycle.
|
| Experimental: MK-1775 125 mg QD x2 Multi + Gemcitabine 1000 mg/ m^2 Participants received gemcitabine 1000 mg/m^2 as an IV infusion on Days 1, 8, and 15 of each 4 week cycle plus MK-1775 125 mg orally QD on Days 1, 2, 8, 9, 15, and 16 of each 4 week cycle. |
Drug: MK-1775
MK-1775 administered as an oral formulation as either monotherapy or in combination with either gemcitabine, cisplatin, or carboplatin.
Drug: gemcitabine
Gemcitabine administered at 1000 mg/m^2 by IV infusion in a 28-day cycle.
|
| Experimental: MK-1775 150 mg QD x2 Multi + Gemcitabine 1000 mg/ m^2 Participants received gemcitabine 1000 mg/m^2 as an IV infusion on Days 1, 8, and 15 of each 4 week cycle plus MK-1775 150 mg orally QD on Days 1, 2, 8, 9, 15, and 16 of each 4 week cycle. |
Drug: MK-1775
MK-1775 administered as an oral formulation as either monotherapy or in combination with either gemcitabine, cisplatin, or carboplatin.
Drug: gemcitabine
Gemcitabine administered at 1000 mg/m^2 by IV infusion in a 28-day cycle.
|
| Experimental: MK-1775 175 mg QD x2 Multi Dose + Gemcitabine 1000 mg/ m^2 Participants received gemcitabine 1000 mg/m^2 as an IV infusion given on Days 1, 8, and 15 of each 4 week cycle plus MK-1775 175 mg orally QD on Days 1, 2, 8, 9, 15, and 16 of each 4 week cycle. |
Drug: MK-1775
MK-1775 administered as an oral formulation as either monotherapy or in combination with either gemcitabine, cisplatin, or carboplatin.
Drug: gemcitabine
Gemcitabine administered at 1000 mg/m^2 by IV infusion in a 28-day cycle.
|
| Experimental: MK-1775 200 mg QD x2 Multi Dose + Gemcitabine 1000 mg/ m^2 Participants received gemcitabine 1000 mg/m^2 as an IV infusion on Days 1, 8, and 15 of each 4 week cycle plus MK-1775 200 mg orally QD on Days 1, 2, 8, 9, 15, and 16 of each 4 week cycle. |
Drug: MK-1775
MK-1775 administered as an oral formulation as either monotherapy or in combination with either gemcitabine, cisplatin, or carboplatin.
Drug: gemcitabine
Gemcitabine administered at 1000 mg/m^2 by IV infusion in a 28-day cycle.
|
| Experimental: MK-1775 50 mg BID x2.5 Multi Dose + Cisplatin 75 mg/ m^2 Participants received cisplatin 75 mg/ m^2 as an IV infusion on Day 1 of each 3 week cycle plus MK-1775 50 mg orally BID for 2.5 days, starting concomitantly with the administration of cisplatin on Day 1 and then at 12 hour intervals on Days 1-3 of each 3 week cycle. |
Drug: MK-1775
MK-1775 administered as an oral formulation as either monotherapy or in combination with either gemcitabine, cisplatin, or carboplatin.
Drug: cisplatin
Cisplatin administered at 75 mg/m^2 by IV infusion in a 21-day cycle.
|
| Experimental: MK-1775 100 mg BID x2.5 Multi Dose + Cisplatin 75 mg/ m^2 Participants received cisplatin 75 mg/ m^2 as an IV infusion on Day 1 of each 3 week cycle plus MK-1775 100 mg orally BID for 2.5 days, starting concomitantly with the administration of cisplatin on Day 1 and then at 12 hour intervals on Days 1-3 of each 3 week cycle. |
Drug: MK-1775
MK-1775 administered as an oral formulation as either monotherapy or in combination with either gemcitabine, cisplatin, or carboplatin.
Drug: cisplatin
Cisplatin administered at 75 mg/m^2 by IV infusion in a 21-day cycle.
|
| Experimental: MK-1775 125 mg BID x2.5 Multi Dose + Cisplatin 75 mg/ m^2 Participants received cisplatin 75 mg/ m^2 as an IV infusion on Day 1 of each 3 week cycle plus MK-1775 125 mg orally BID for 2.5 days, starting concomitantly with the administration of cisplatin on Day 1 and then at 12 hour intervals on Days 1-3 of each 3 week cycle. |
Drug: MK-1775
MK-1775 administered as an oral formulation as either monotherapy or in combination with either gemcitabine, cisplatin, or carboplatin.
Drug: cisplatin
Cisplatin administered at 75 mg/m^2 by IV infusion in a 21-day cycle.
|
| Experimental: MK-1775 150 mg BID x2.5 Multi Dose + Cisplatin 75 mg/ m^2 Participants received cisplatin 75 mg/ m^2 as an IV infusion on Day 1 of each 3 week cycle plus MK-1775 150 mg orally BID for 2.5 days, starting concomitantly with the administration of cisplatin on Day 1 and then at 12 hour intervals on Days 1-3 of each 3 week cycle. |
Drug: MK-1775
MK-1775 administered as an oral formulation as either monotherapy or in combination with either gemcitabine, cisplatin, or carboplatin.
Drug: cisplatin
Cisplatin administered at 75 mg/m^2 by IV infusion in a 21-day cycle.
|
| Experimental: MK-1775 200 mg BID x2.5 Multi Dose + Cisplatin 75 mg/ m^2 Participants received cisplatin 75 mg/ m^2 as an IV infusion on Day 1 of each 3 week cycle plus MK-1775 200 mg orally BID for 2.5 days, starting concomitantly with the administration of cisplatin on Day 1 and then at 12 hour intervals on Days 1-3 of each 3 week cycle. |
Drug: MK-1775
MK-1775 administered as an oral formulation as either monotherapy or in combination with either gemcitabine, cisplatin, or carboplatin.
Drug: cisplatin
Cisplatin administered at 75 mg/m^2 by IV infusion in a 21-day cycle.
|
| Experimental: MK-1775 250 mg BID x2.5 Multi Dose + Cisplatin 75 mg/ m^2 Participants received cisplatin 75 mg/ m^2 as an IV infusion on Day 1 of each 3 week cycle plus MK-1775 250 mg orally BID for 2.5 days, starting concomitantly with the administration of cisplatin on Day 1 and then at 12 hour intervals on Days 1-3 of each 3 week cycle. |
Drug: MK-1775
MK-1775 administered as an oral formulation as either monotherapy or in combination with either gemcitabine, cisplatin, or carboplatin.
Drug: cisplatin
Cisplatin administered at 75 mg/m^2 by IV infusion in a 21-day cycle.
|
| Experimental: MK-1775 75 mg BID x2.5 Multi Dose + Carboplatin AUC 5 Participants received carboplatin AUC 5 as an IV infusion on Day 1 of each 3 week cycle plus MK-1775 75 mg orally BID for 2.5 days, starting concomitantly with the administration of carboplatin on Day 1 and then at 12 hour intervals on Days 1-3 of each 3 week cycle. |
Drug: MK-1775
MK-1775 administered as an oral formulation as either monotherapy or in combination with either gemcitabine, cisplatin, or carboplatin.
Drug: carboplatin
Carboplatin administered at AUC/time curve of 5 mg/min/mL (AUC5) by IV infusion in a 21-day cycle.
|
| Experimental: MK-1775 150 mg BID x 2.5 Multi Dose + Carboplatin AUC 5 Participants received carboplatin AUC 5 as an IV infusion on Day 1 of each 3 week cycle plus MK-1775 150 mg orally BID for 2.5 days, starting concomitantly with the administration of carboplatin on Day 1 and then at 12 hour intervals on Days 1-3 of each 3 week cycle. |
Drug: MK-1775
MK-1775 administered as an oral formulation as either monotherapy or in combination with either gemcitabine, cisplatin, or carboplatin.
Drug: carboplatin
Carboplatin administered at AUC/time curve of 5 mg/min/mL (AUC5) by IV infusion in a 21-day cycle.
|
| Experimental: MK-1775 225 mg BID x2.5 Multi Dose + Carboplatin AUC 5 Participants received carboplatin AUC 5 as an IV infusion on Day 1 of each 3 week cycle plus MK-1775 225 mg orally BID for 2.5 days, starting concomitantly with the administration of carboplatin on Day 1 and then at 12 hour intervals on Days 1-3 of each 3 week cycle. |
Drug: MK-1775
MK-1775 administered as an oral formulation as either monotherapy or in combination with either gemcitabine, cisplatin, or carboplatin.
Drug: carboplatin
Carboplatin administered at AUC/time curve of 5 mg/min/mL (AUC5) by IV infusion in a 21-day cycle.
|
| Experimental: MK-1775 325 mg BID x2.5 Multi Dose + Carboplatin AUC 5 Participants received carboplatin AUC 5 as an IV infusion on Day 1 of each 3 week cycle plus MK-1775 325 mg orally BID for 2.5 days, starting concomitantly with the administration of carboplatin on Day 1 and then at 12 hour intervals on Days 1-3 of each 3 week cycle. |
Drug: MK-1775
MK-1775 administered as an oral formulation as either monotherapy or in combination with either gemcitabine, cisplatin, or carboplatin.
Drug: carboplatin
Carboplatin administered at AUC/time curve of 5 mg/min/mL (AUC5) by IV infusion in a 21-day cycle.
|
Outcome Measures
Primary Outcome Measures
- Number of Participants Experiencing Dose-Limiting Toxicities (DLTs) [Part 1: Up to 14 days, Part 2: Up to 28 days]
DLTs were adverse events (AEs) considered at least possibly related to study drug that prevented escalation of the drug dose. Hematologic DLTs were any grade (Gr) 4-5 toxicity EXCEPT: Gr 4 anemia and Gr 4 leukopenia, Gr 4 neutropenia lasting for <7 days, Gr 4 thrombocytopenia lasting for <4 days except if a platelet transfusion is required, and Gr 3/Gr 4 neutropenia with fever >38.5°C and/or infection requiring antibiotic or anti-fungal treatment. Non-hematologic DLT was defined as any Gr 3, 4, or 5 non-hematologic toxicity EXCEPT: nausea, vomiting, diarrhea, or dehydration (all Gr 3) occurring in a setting of inadequate compliance with supportive care measures and lasting for <48 hours, alopecia of any grade, inadequately treated hypersensitivity reactions, and clinically non-significant, treatable or reversible lab abnormalities including liver function tests, uric acid, etc.
- Percentage of Total Cyclin-dependent Kinase (CDC2)-Positive Cells That Were Phosphorylated (pCDC2) in Skin Cells at Baseline and 8 Hours After MK-1775 Dosing [Baseline, 8 hours after first MK-1775 dose]
The pCDC2 level in skin cells was used as a marker to evaluate MK-1775 activity. Analysis was done by immunohistochemistry and the percentage of total CDC2-positive cells that were pCDC2 positive (% pCDC2-positive cells) at baseline and 8 hours after MK-1775 dosing were reported for participants in Part 1, 2-A, and 2-B/3 treatment groups with available data per protocol.
- Percentage of Total pCDC2 in Skin Cells at Baseline and 24 Hours After MK-1775 Dosing [Baseline, 24 hours after first MK-1775 dose]
The pCDC2 level in skin cells was used as a marker to evaluate MK-1775 activity. Analysis was done by immunohistochemistry and the percentage of total pCDC2 at baseline and 24 hours after MK-1775 dosing were reported for participants in the Part 2-B/3 MK-1775 QD x2 Multi Dose plus Gemcitabine treatment groups with available data per protocol.
- Percentage of Total pCDC2 in Skin Cells at Baseline and 48 Hours After MK-1775 Dosing [Baseline, 48 hours after first MK-1775 dose]
The pCDC2 level in skin cells was used as a marker to evaluate MK-1775 activity. Analysis was done by immunohistochemistry and the percentage of total pCDC2 at baseline and at 48 hours after MK-1775 dosing were reported for participants in the Part 2-B/3 MK-1775 (150 mg, 200 mg, 250) BID x 2.5 Multi Dose plus cisplatin 75 mg/m^2 groups and the 325 mg BID x2.5 Multi Dose + Carboplatin group with available data per protocol.
- Plasma Concentration of MK-1775 at 8 Hours After Administration (C8hr) of Single or Multiple Oral Doses [8 hours after MK-1775 dose]
MK-1775 was measured in the plasma at 8 hours after dosing (Day 1 for single dose of monotherapy, Day 2 of single-dose combination therapy and QD x 2 Combination dosing, and Day 3 dose for BID X 2.5 combination dosing) for participants with available data.
- Mean Urine Excretion of MK-1775 24 Hours After the Day 1 Monotherapy Dose [At 0-4 hours, 4-8 hours, and 12-24 hours post Day 1 dose of monotherapy]
The mean cumulative amount of MK-1775 excreted unchanged in urine after a single oral dose was measured during the initial monotherapy cycle of the study. For this outcome measure, samples were collected and analyzed only for the MK-1775 monotherapy arms of the study at defined intervals after the Day 1 dose of monotherapy. Part 2 MK-1775 combination arms were not sampled per protocol.
Secondary Outcome Measures
- Best Overall Response as Per Response Evaluation Criteria in Solid Tumors (RECIST) Criteria [From Day 1 up through discontinuation of study treatment (up to ~11.2 months)]
Best overall response achieved by a participant. Starting at Day 1, participants in Part 2 were evaluated for tumor response every 6-8 weeks until discontinuation from study treatment according to RECIST criteria; which are based on radiographic imaging. Recorded responses were either confirmed by Central Review or unconfirmed (Investigator assessment only), and included complete response (CR; defined as disappearance of all target lesions), partial response (PR; at least a 30% decrease in the sum of the longest diameter [LD] of target lesions, taking as reference the baseline sum LD), stable disease (SD; neither sufficient shrinkage to qualify for PR nor sufficient growth to qualify for PD, taking as reference the smallest sum LD since the treatment started), or progressive disease (PD; ≥20% increase in sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started, or the appearance of one or more new lesions).
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Must have a histologically confirmed metastatic or locally advanced solid tumor, progressed despite standard therapy, or for which standard therapy does not exist
-
Must have performance status of <=1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale
-
Female participants must not be pregnant
Exclusion Criteria:
-
Has had chemotherapy, radiotherapy, or biological therapy within 4 weeks prior to entering the study or who has not recovered from adverse events due to agents given more than 4 weeks earlier
-
Is participating or has participated in a study with an investigational compound or device within 30 days
-
Has active central nervous system (CNS) metastases and/or carcinomatous meningitis. However, participants with CNS metastases who have completed a course of therapy would be eligible for the study provided they are clinically stable for 1 month prior to entry
-
Has a primary central nervous system tumor
-
Is allergic to any of the components of the combination study therapy or its analogs
-
Participant has had prescription or non-prescription drugs or other products known to be metabolized by Cytochrome P450 3A4 (CYP3A4) that cannot be discontinued prior to Day 1 of dosing and withheld throughout the study until 2 weeks after the last dose of study medication. Medications of particular concern are inhibitors of CYP3A4 (azole antifungals [ketoconazole, itraconazole], macrolide antibiotics [erythromycin, clarithromycin], cimetidine, aprepitant, Human Immunodeficiency Virus (HIV) protease inhibitors, nefrazodone, and the following inducers of CYP3A4: phenytoin, barbiturates and rifampicin, and substrates of CYP3A4 including statins (lovastatin, simvastatin), midazolam, terfenadine, astemizole, and cisapride
-
Is a regular user (including "recreational use") of any illicit drugs or had a recent history (within the last year) of drug or alcohol abuse
-
Pregnant or breastfeeding, or expecting to get pregnant during the time the study will be ongoing
-
HIV-positive
-
History of Hepatitis B or C
-
Has symptomatic ascites or pleural effusion. A participant who is clinically stable following treatment for these conditions is eligible
-
Participant must not have prior radiation therapy to more than 30% of the bone marrow and must have recovered for at least 3 weeks from the hematologic toxicity of prior radiotherapy
-
Has had a prior stem cell or bone marrow transplant
-
Has received more than 4 prior cytotoxic chemotherapy regimens
-
Has a history suggestive of Li-Fraumeni Syndrome
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
Publications
None provided.Responsible Party:
Merck Sharp & Dohme LLC
ClinicalTrials.gov Identifier:
NCT00648648
Other Study ID Numbers:
- 1775-001
- 2007_611
- 2007-005304-40
- MK-1775-001
First Posted:
Apr 1, 2008
Last Update Posted:
Apr 5, 2019
Last Verified:
Jan 1, 2019
Individual Participant Data (IPD) Sharing Statement:
Yes
Plan to Share IPD:
Yes
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail | 206 participants were allocated to one of 28 treatment arms (3 Part 1 arms and 25 Part 2 arms). 8 participants from the Part 1 MK-1775 monotherapy arms continued into Part 2 of the study and received single dose (SD) combination treatment. For disposition purposes these participants are counted under Part 1 only. |
| Arm/Group Title | MK-1775 325 mg Single Dose | MK-1775 650 mg Single Dose | MK-1775 1300 mg Single Dose | MK-1775 100 mg Single Dose + Gemcitabine 1000 mg/m^2 | MK-1775 200 mg Single Dose + Gemcitabine 1000 mg/m^2 | MK-1775 100 mg Single Dose + Cisplatin 75 mg/ m^2 | MK-1775 200 mg Single Dose + Cisplatin 75 mg/ m^2 | MK-1775 100 mg Single Dose + Carboplatin AUC 5 | MK-1775 200 mg Single Dose + Carboplatin AUC 5 | MK-1775 325 mg Single Dose + Carboplatin AUC 5 | MK-1775 25 mg BID x2.5 Multi Dose + Gemcitabine 1000 mg/ m^2 | MK-1775 50/25 mg BID x2.5 Multi + Gemcitabine 1000 mg/ m^2 | MK-1775 50 mg BID x2.5 Multi + Gemcitabine 1000 mg/ m^2 | MK-1775 100 mg QD x2 Multi + Gemcitabine 1000 mg/ m^2 | MK-1775 125 mg QD x2 Multi + Gemcitabine 1000 mg/ m^2 | MK-1775 150 mg QD x2 Multi + Gemcitabine 1000 mg/ m^2 | MK-1775 175 mg QD x2 Multi Dose + Gemcitabine 1000 mg/ m^2 | MK-1775 200 mg QD x2 Multi Dose + Gemcitabine 1000 mg/ m^2 | MK-1775 50 mg BID x2.5 Multi Dose + Cisplatin 75 mg/ m^2 | MK-1775 100 mg BID x2.5 Multi Dose + Cisplatin 75 mg/ m^2 | MK-1775 125 mg BID x2.5 Multi Dose + Cisplatin 75 mg/ m^2 | MK-1775 150 mg BID x2.5 Multi Dose + Cisplatin 75 mg/ m^2 | MK-1775 200 mg BID x2.5 Multi Dose + Cisplatin 75 mg/ m^2 | MK-1775 250 mg BID x2.5 Multi Dose + Cisplatin 75 mg/ m^2 | MK-1775 75 mg BID x2.5 Multi Dose + Carboplatin AUC 5 | MK-1775 150 mg BID x 2.5 Multi Dose + Carboplatin AUC 5 | MK-1775 225 mg BID x2.5 Multi Dose + Carboplatin AUC 5 | MK-1775 325 mg BID x2.5 Multi Dose + Carboplatin AUC 5 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants received MK-1775 325 mg, orally, on Day 1. | Participants received MK-1775 650 mg, orally, on Day 1. | Participants received MK-1775 1300 mg, orally, on Day 1. | Participants received gemcitabine 1000 mg/m^2 as an intravenous (IV) infusion on Days 1, 8, and 15 in each 4-week cycle plus MK-1775 100 mg single dose, orally, on Day 2 of each cycle. | Participants received gemcitabine 1000 mg/m^2 as an IV infusion on Days 1, 8, and 15 in each 4-week cycle plus MK-1775 200 mg single dose, orally, on Day 2 of each cycle. | Participants received cisplatin 75 mg/ m^2 as an IV infusion on Day 1 of each 3 week cycle plus MK-1775 100 mg single dose orally, on Day 2 of each cycle. | Participants received cisplatin 75 mg/ m^2 as an IV infusion on Day 1 of each 3 week cycle plus MK-1775 200 mg single dose orally, on Day 2 of each cycle. | Participants received carboplatin at an area under the time curve concentration of 5 mg/min/ml (AUC5) as an IV infusion on Day 1 of each 3 week cycle plus MK-1775 100 mg single dose orally, on Day 2 of each cycle. | Participants received carboplatin AUC5 as an IV infusion on Day 1 of each 3 week cycle plus MK-1775 200 mg single dose orally, on Day 2 of each cycle. | Participants received carboplatin AUC5 as an IV infusion on Day 1 of each 3 week cycle plus MK-1775 325 mg single dose orally, on Day 2 of each cycle. | Participants received gemcitabine 1000 mg/m^2 as an IV infusion on Days 1, 8, and 15 of each 4-week cycle plus MK-1775 25 mg orally twice daily (BID) for 2.5 days, starting concomitantly with the IV infusion of gemcitabine on Day 1 and followed by 4 additional doses of MK-1775 25 mg at approximately 12 hour intervals on Days 1-3, 8-9, and 15-17 of each cycle. | Participants received gemcitabine 1000 mg/m^2 as an IV infusion on Days 1, 8, and 15 of each 4 week cycle plus MK-1775 50 mg orally BID for 2.5 days, starting concomitantly with the IV infusion of gemcitabine on Day 1 and followed by 4 doses of MK-1775 25 mg at approximately 12 hour intervals on Days 1-3, 8-9, and 15-17 of each 4 week cycle. | Participants received gemcitabine 1000 mg/m^2 as an IV infusion given once weekly for 3 consecutive weeks of a 4 week cycle plus MK-1775 50 mg orally BID for 2.5 days, starting concomitantly with the IV infusion of gemcitabine on Day 1 and followed by 4 additional doses of MK-1775 50 mg at approximately 12 hour intervals on Days 1-3, 8-9, and 15-17 of each 4 week cycle. | Participants received gemcitabine 1000 mg/m^2 as an IV infusion on Days 1, 8, and 15 of each 4 week cycle plus MK-1775 100 mg orally once daily (QD) on Days 1, 2, 8, 9, 15, and 16 of each 4 week cycle. | Participants received gemcitabine 1000 mg/m^2 as an IV infusion on Days 1, 8, and 15 of each 4 week cycle plus MK-1775 125 mg orally QD on Days 1, 2, 8, 9, 15, and 16 of each 4 week cycle. | Participants received gemcitabine 1000 mg/m^2 as an IV infusion on Days 1, 8, and 15 of each 4 week cycle plus MK-1775 150 mg orally QD on Days 1, 2, 8, 9, 15, and 16 of each 4 week cycle. | Participants received gemcitabine 1000 mg/m^2 as an IV infusion given on Days 1, 8, and 15 of each 4 week cycle plus MK-1775 175 mg orally QD on Days 1, 2, 8, 9, 15, and 16 of each 4 week cycle. | Participants received gemcitabine 1000 mg/m^2 as an IV infusion on Days 1, 8, and 15 of each 4 week cycle plus MK-1775 200 mg orally QD on Days 1, 2, 8, 9, 15, and 16 of each 4 week cycle. | Participants received cisplatin 75 mg/ m^2 as an IV infusion on Day 1 of each 3 week cycle plus MK-1775 50 mg orally BID for 2.5 days, starting concomitantly with the administration of cisplatin on Day 1 and then at 12 hour intervals on Days 1-3 of each 3 week cycle. | Participants received cisplatin 75 mg/ m^2 as an IV infusion on Day 1 of each 3 week cycle plus MK-1775 100 mg orally BID for 2.5 days, starting concomitantly with the administration of cisplatin on Day 1 and then at 12 hour intervals on Days 1-3 of each 3 week cycle. | Participants received cisplatin 75 mg/ m^2 as an IV infusion on Day 1 of each 3 week cycle plus MK-1775 125 mg orally BID for 2.5 days, starting concomitantly with the administration of cisplatin on Day 1 and then at 12 hour intervals on Days 1-3 of each 3 week cycle. | Participants received cisplatin 75 mg/ m^2 as an IV infusion on Day 1 of each 3 week cycle plus MK-1775 150 mg orally BID for 2.5 days, starting concomitantly with the administration of cisplatin on Day 1 and then at 12 hour intervals on Days 1-3 of each 3 week cycle. | Participants received cisplatin 75 mg/ m^2 as an IV infusion on Day 1 of each 3 week cycle plus MK-1775 200 mg orally BID for 2.5 days, starting concomitantly with the administration of cisplatin on Day 1 and then at 12 hour intervals on Days 1-3 of each 3 week cycle. | Participants received cisplatin 75 mg/ m^2 as an IV infusion on Day 1 of each 3 week cycle plus MK-1775 250 mg orally BID for 2.5 days, starting concomitantly with the administration of cisplatin on Day 1 and then at 12 hour intervals on Days 1-3 of each 3 week cycle. | Participants received carboplatin AUC 5 as an IV infusion on Day 1 of each 3 week cycle plus MK-1775 75 mg orally BID for 2.5 days, starting concomitantly with the administration of carboplatin on Day 1 and then at 12 hour intervals on Days 1-3 of each 3 week cycle. | Participants received carboplatin AUC 5 as an IV infusion on Day 1 of each 3 week cycle plus MK-1775 150 mg orally BID for 2.5 days, starting concomitantly with the administration of carboplatin on Day 1 and then at 12 hour intervals on Days 1-3 of each 3 week cycle. | Participants received carboplatin AUC 5 as an IV infusion on Day 1 of each 3 week cycle plus MK-1775 225 mg orally BID for 2.5 days, starting concomitantly with the administration of carboplatin on Day 1 and then at 12 hour intervals on Days 1-3 of each 3 week cycle. | Participants received carboplatin AUC 5 as an IV infusion on Day 1 of each 3 week cycle plus MK-1775 325 mg orally BID for 2.5 days, starting concomitantly with the administration of carboplatin on Day 1 and then at 12 hour intervals on Days 1-3 of each 3 week cycle. |
| Period Title: Overall Study | ||||||||||||||||||||||||||||
| STARTED | 3 | 3 | 3 | 4 | 9 | 1 | 10 | 1 | 3 | 10 | 6 | 13 | 6 | 5 | 4 | 11 | 16 | 6 | 5 | 7 | 6 | 10 | 14 | 4 | 4 | 4 | 26 | 12 |
| Treated | 3 | 3 | 3 | 4 | 8 | 1 | 9 | 1 | 3 | 9 | 6 | 13 | 6 | 5 | 4 | 11 | 16 | 6 | 4 | 7 | 6 | 10 | 14 | 4 | 4 | 4 | 26 | 12 |
| COMPLETED | 3 | 3 | 3 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| NOT COMPLETED | 0 | 0 | 0 | 4 | 9 | 1 | 10 | 1 | 3 | 10 | 6 | 13 | 6 | 5 | 4 | 11 | 14 | 6 | 5 | 7 | 6 | 10 | 14 | 4 | 4 | 4 | 26 | 12 |
Baseline Characteristics
| Arm/Group Title | MK-1775 325 mg Single Dose | MK-1775 650 mg Single Dose | MK-1775 1300 mg Single Dose | MK-1775 100 mg Single Dose + Gemcitabine 1000 mg/m^2 | MK-1775 200 mg Single Dose + Gemcitabine 1000 mg/m^2 | MK-1775 100 mg Single Dose + Cisplatin 75 mg/ m^2 | MK-1775 200 mg Single Dose + Cisplatin 75 mg/ m^2 | MK-1775 100 mg Single Dose + Carboplatin AUC 5 | MK-1775 200 mg Single Dose + Carboplatin AUC 5 | MK-1775 325 mg Single Dose + Carboplatin AUC 5 | MK-1775 25 mg BID x2.5 Multi Dose + Gemcitabine 1000 mg/ m^2 | MK-1775 50/25 mg BID x2.5 Multi + Gemcitabine 1000 mg/ m^2 | MK-1775 50 mg BID x2.5 Multi + Gemcitabine 1000 mg/ m^2 | MK-1775 100 mg QD x2 Multi + Gemcitabine 1000 mg/ m^2 | MK-1775 125 mg QD x2 Multi + Gemcitabine 1000 mg/ m^2 | MK-1775 150 mg QD x2 Multi + Gemcitabine 1000 mg/ m^2 | MK-1775 175 mg QD x2 Multi Dose + Gemcitabine 1000 mg/ m^2 | MK-1775 200 mg QD x2 Multi Dose + Gemcitabine 1000 mg/ m^2 | MK-1775 50 mg BID x2.5 Multi Dose + Cisplatin 75 mg/ m^2 | MK-1775 100 mg BID x2.5 Multi Dose + Cisplatin 75 mg/ m^2 | MK-1775 125 mg BID x2.5 Multi Dose + Cisplatin 75 mg/ m^2 | MK-1775 150 mg BID x2.5 Multi Dose + Cisplatin 75 mg/ m^2 | MK-1775 200 mg BID x2.5 Multi Dose + Cisplatin 75 mg/ m^2 | MK-1775 250 mg BID x2.5 Multi Dose + Cisplatin 75 mg/ m^2 | MK-1775 75 mg BID x2.5 Multi Dose + Carboplatin AUC 5 | MK-1775 150 mg BID x 2.5 Multi Dose + Carboplatin AUC 5 | MK-1775 225 mg BID x2.5 Multi Dose + Carboplatin AUC 5 | MK-1775 325 mg BID x2.5 Multi Dose + Carboplatin AUC 5 | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants received MK-1775 325 mg, orally, on Day 1. | Participants received MK-1775 650 mg, orally, on Day 1. | Participants received MK-1775 1300 mg, orally, on Day 1. | Participants received gemcitabine 1000 mg/m^2 as an intravenous (IV) infusion on Days 1, 8, and 15 in each 4-week cycle plus MK-1775 100 mg single dose, orally, on Day 2 of each cycle. | Participants received gemcitabine 1000 mg/m^2 as an IV infusion on Days 1, 8, and 15 in each 4-week cycle plus MK-1775 200 mg single dose, orally, on Day 2 of each cycle. | Participants received cisplatin 75 mg/ m^2 as an IV infusion on Day 1 of each 3 week cycle plus MK-1775 100 mg single dose orally, on Day 2 of each cycle. | Participants received cisplatin 75 mg/ m^2 as an IV infusion on Day 1 of each 3 week cycle plus MK-1775 200 mg single dose orally, on Day 2 of each cycle. | Participants received carboplatin at an area under the time curve concentration of 5 mg/min/ml (AUC5) as an IV infusion on Day 1 of each 3 week cycle plus MK-1775 100 mg single dose orally, on Day 2 of each cycle. | Participants received carboplatin AUC5 as an IV infusion on Day 1 of each 3 week cycle plus MK-1775 200 mg single dose orally, on Day 2 of each cycle. | Participants received carboplatin AUC5 as an IV infusion on Day 1 of each 3 week cycle plus MK-1775 325 mg single dose orally, on Day 2 of each cycle. | Participants received gemcitabine 1000 mg/m^2 as an IV infusion on Days 1, 8, and 15 of each 4-week cycle plus MK-1775 25 mg orally twice daily (BID) for 2.5 days, starting concomitantly with the IV infusion of gemcitabine on Day 1 and followed by 4 additional doses of MK-1775 25 mg at approximately 12 hour intervals on Days 1-3, 8-9, and 15-17 of each cycle. | Participants received gemcitabine 1000 mg/m^2 as an IV infusion on Days 1, 8, and 15 of each 4 week cycle plus MK-1775 50 mg orally BID for 2.5 days, starting concomitantly with the IV infusion of gemcitabine on Day 1 and followed by 4 doses of MK-1775 25 mg at approximately 12 hour intervals on Days 1-3, 8-9, and 15-17 of each 4 week cycle. | Participants received gemcitabine 1000 mg/m^2 as an IV infusion given once weekly for 3 consecutive weeks of a 4 week cycle plus MK-1775 50 mg orally BID for 2.5 days, starting concomitantly with the IV infusion of gemcitabine on Day 1 and followed by 4 additional doses of MK-1775 50 mg at approximately 12 hour intervals on Days 1-3, 8-9, and 15-17 of each 4 week cycle. | Participants received gemcitabine 1000 mg/m^2 as an IV infusion on Days 1, 8, and 15 of each 4 week cycle plus MK-1775 100 mg orally once daily (QD) on Days 1, 2, 8, 9, 15, and 16 of each 4 week cycle. | Participants received gemcitabine 1000 mg/m^2 as an IV infusion on Days 1, 8, and 15 of each 4 week cycle plus MK-1775 125 mg orally QD on Days 1, 2, 8, 9, 15, and 16 of each 4 week cycle. | Participants received gemcitabine 1000 mg/m^2 as an IV infusion on Days 1, 8, and 15 of each 4 week cycle plus MK-1775 150 mg orally QD on Days 1, 2, 8, 9, 15, and 16 of each 4 week cycle. | Participants received gemcitabine 1000 mg/m^2 as an IV infusion given on Days 1, 8, and 15 of each 4 week cycle plus MK-1775 175 mg orally QD on Days 1, 2, 8, 9, 15, and 16 of each 4 week cycle. | Participants received gemcitabine 1000 mg/m^2 as an IV infusion on Days 1, 8, and 15 of each 4 week cycle plus MK-1775 200 mg orally QD on Days 1, 2, 8, 9, 15, and 16 of each 4 week cycle. | Participants received cisplatin 75 mg/ m^2 as an IV infusion on Day 1 of each 3 week cycle plus MK-1775 50 mg orally BID for 2.5 days, starting concomitantly with the administration of cisplatin on Day 1 and then at 12 hour intervals on Days 1-3 of each 3 week cycle. | Participants received cisplatin 75 mg/ m^2 as an IV infusion on Day 1 of each 3 week cycle plus MK-1775 100 mg orally BID for 2.5 days, starting concomitantly with the administration of cisplatin on Day 1 and then at 12 hour intervals on Days 1-3 of each 3 week cycle. | Participants received cisplatin 75 mg/ m^2 as an IV infusion on Day 1 of each 3 week cycle plus MK-1775 125 mg orally BID for 2.5 days, starting concomitantly with the administration of cisplatin on Day 1 and then at 12 hour intervals on Days 1-3 of each 3 week cycle. | Participants received cisplatin 75 mg/ m^2 as an IV infusion on Day 1 of each 3 week cycle plus MK-1775 150 mg orally BID for 2.5 days, starting concomitantly with the administration of cisplatin on Day 1 and then at 12 hour intervals on Days 1-3 of each 3 week cycle. | Participants received cisplatin 75 mg/ m^2 as an IV infusion on Day 1 of each 3 week cycle plus MK-1775 200 mg orally BID for 2.5 days, starting concomitantly with the administration of cisplatin on Day 1 and then at 12 hour intervals on Days 1-3 of each 3 week cycle. | Participants received cisplatin 75 mg/ m^2 as an IV infusion on Day 1 of each 3 week cycle plus MK-1775 250 mg orally BID for 2.5 days, starting concomitantly with the administration of cisplatin on Day 1 and then at 12 hour intervals on Days 1-3 of each 3 week cycle. | Participants received carboplatin AUC 5 as an IV infusion on Day 1 of each 3 week cycle plus MK-1775 75 mg orally BID for 2.5 days, starting concomitantly with the administration of carboplatin on Day 1 and then at 12 hour intervals on Days 1-3 of each 3 week cycle. | Participants received carboplatin AUC 5 as an IV infusion on Day 1 of each 3 week cycle plus MK-1775 150 mg orally BID for 2.5 days, starting concomitantly with the administration of carboplatin on Day 1 and then at 12 hour intervals on Days 1-3 of each 3 week cycle. | Participants received carboplatin AUC 5 as an IV infusion on Day 1 of each 3 week cycle plus MK-1775 225 mg orally BID for 2.5 days, starting concomitantly with the administration of carboplatin on Day 1 and then at 12 hour intervals on Days 1-3 of each 3 week cycle. | Participants received carboplatin AUC 5 as an IV infusion on Day 1 of each 3 week cycle plus MK-1775 325 mg orally BID for 2.5 days, starting concomitantly with the administration of carboplatin on Day 1 and then at 12 hour intervals on Days 1-3 of each 3 week cycle. | Total of all reporting groups |
| Overall Participants | 3 | 3 | 3 | 4 | 9 | 1 | 10 | 1 | 3 | 10 | 6 | 13 | 6 | 5 | 4 | 11 | 16 | 6 | 5 | 7 | 6 | 10 | 14 | 4 | 4 | 4 | 26 | 12 | 206 |
| Age (years) [Mean (Standard Deviation) ] | |||||||||||||||||||||||||||||
| Mean (Standard Deviation) [years] |
64.0
(13.7)
|
44.0
(8.5)
|
67.7
(19.5)
|
47.0
(19.6)
|
60.6
(12.6)
|
58.0
(0)
|
61.5
(10.2)
|
75.0
(0)
|
64.7
(4.0)
|
55.6
(13.0)
|
56.2
(6.8)
|
55.1
(12.5)
|
64.5
(10.7)
|
49.8
(18.4)
|
60.5
(8.3)
|
64.7
(9.1)
|
64.8
(8.9)
|
57.8
(8.8)
|
55.2
(7.5)
|
56.1
(14.6)
|
48.8
(12.4)
|
51.5
(8.8)
|
52.6
(9.4)
|
62.3
(3.3)
|
61.0
(9.6)
|
65.8
(8.8)
|
56.2
(12.8)
|
58.5
(12.6)
|
57.9
(11.9)
|
| Sex: Female, Male (Count of Participants) | |||||||||||||||||||||||||||||
| Female |
2
66.7%
|
2
66.7%
|
2
66.7%
|
2
50%
|
8
88.9%
|
0
0%
|
4
40%
|
0
0%
|
0
0%
|
5
50%
|
3
50%
|
10
76.9%
|
3
50%
|
3
60%
|
1
25%
|
5
45.5%
|
11
68.8%
|
3
50%
|
3
60%
|
2
28.6%
|
3
50%
|
5
50%
|
10
71.4%
|
4
100%
|
2
50%
|
2
50%
|
14
53.8%
|
7
58.3%
|
116
56.3%
|
| Male |
1
33.3%
|
1
33.3%
|
1
33.3%
|
2
50%
|
1
11.1%
|
1
100%
|
6
60%
|
1
100%
|
3
100%
|
5
50%
|
3
50%
|
3
23.1%
|
3
50%
|
2
40%
|
3
75%
|
6
54.5%
|
5
31.3%
|
3
50%
|
2
40%
|
5
71.4%
|
3
50%
|
5
50%
|
4
28.6%
|
0
0%
|
2
50%
|
2
50%
|
12
46.2%
|
5
41.7%
|
90
43.7%
|
Outcome Measures
| Title | Number of Participants Experiencing Dose-Limiting Toxicities (DLTs) |
|---|---|
| Description | DLTs were adverse events (AEs) considered at least possibly related to study drug that prevented escalation of the drug dose. Hematologic DLTs were any grade (Gr) 4-5 toxicity EXCEPT: Gr 4 anemia and Gr 4 leukopenia, Gr 4 neutropenia lasting for <7 days, Gr 4 thrombocytopenia lasting for <4 days except if a platelet transfusion is required, and Gr 3/Gr 4 neutropenia with fever >38.5°C and/or infection requiring antibiotic or anti-fungal treatment. Non-hematologic DLT was defined as any Gr 3, 4, or 5 non-hematologic toxicity EXCEPT: nausea, vomiting, diarrhea, or dehydration (all Gr 3) occurring in a setting of inadequate compliance with supportive care measures and lasting for <48 hours, alopecia of any grade, inadequately treated hypersensitivity reactions, and clinically non-significant, treatable or reversible lab abnormalities including liver function tests, uric acid, etc. |
| Time Frame | Part 1: Up to 14 days, Part 2: Up to 28 days |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received at least one dose of study treatment and were evaluable for DLT. |
| Arm/Group Title | MK-1775 325 mg Single Dose | MK-1775 650 mg Single Dose | MK-1775 1300 mg Single Dose | MK-1775 100 mg Single Dose + Gemcitabine 1000 mg/m^2 | MK-1775 200 mg Single Dose + Gemcitabine 1000 mg/m^2 | MK-1775 100 mg Single Dose + Cisplatin 75 mg/ m^2 | MK-1775 200 mg Single Dose + Cisplatin 75 mg/ m^2 | MK-1775 100 mg Single Dose + Carboplatin AUC 5 | MK-1775 200 mg Single Dose + Carboplatin AUC 5 | MK-1775 325 mg Single Dose + Carboplatin AUC 5 | MK-1775 25 mg BID x2.5 Multi Dose + Gemcitabine 1000 mg/ m^2 | MK-1775 50/25 mg BID x2.5 Multi + Gemcitabine 1000 mg/ m^2 | MK-1775 50 mg BID x2.5 Multi + Gemcitabine 1000 mg/ m^2 | MK-1775 100 mg QD x2 Multi + Gemcitabine 1000 mg/ m^2 | MK-1775 125 mg QD x2 Multi + Gemcitabine 1000 mg/ m^2 | MK-1775 150 mg QD x2 Multi + Gemcitabine 1000 mg/ m^2 | MK-1775 175 mg QD x2 Multi Dose + Gemcitabine 1000 mg/ m^2 | MK-1775 200 mg QD x2 Multi Dose + Gemcitabine 1000 mg/ m^2 | MK-1775 50 mg BID x2.5 Multi Dose + Cisplatin 75 mg/ m^2 | MK-1775 100 mg BID x2.5 Multi Dose + Cisplatin 75 mg/ m^2 | MK-1775 125 mg BID x2.5 Multi Dose + Cisplatin 75 mg/ m^2 | MK-1775 150 mg BID x2.5 Multi Dose + Cisplatin 75 mg/ m^2 | MK-1775 200 mg BID x2.5 Multi Dose + Cisplatin 75 mg/ m^2 | MK-1775 250 mg BID x2.5 Multi Dose + Cisplatin 75 mg/ m^2 | MK-1775 75 mg BID x2.5 Multi Dose + Carboplatin AUC 5 | MK-1775 150 mg BID x 2.5 Multi Dose + Carboplatin AUC 5 | MK-1775 225 mg BID x2.5 Multi Dose + Carboplatin AUC 5 | MK-1775 325 mg BID x2.5 Multi Dose + Carboplatin AUC 5 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants received MK-1775 325 mg, orally, on Day 1. | Participants received MK-1775 650 mg, orally, on Day 1. | Participants received MK-1775 1300 mg, orally, on Day 1. | Participants received gemcitabine 1000 mg/m^2 as an intravenous (IV) infusion on Days 1, 8, and 15 in each 4-week cycle plus MK-1775 100 mg single dose, orally, on Day 2 of each cycle. | Participants received gemcitabine 1000 mg/m^2 as an IV infusion on Days 1, 8, and 15 in each 4-week cycle plus MK-1775 200 mg single dose, orally, on Day 2 of each cycle. | Participants received cisplatin 75 mg/ m^2 as an IV infusion on Day 1 of each 3 week cycle plus MK-1775 100 mg single dose orally, on Day 2 of each cycle. | Participants received cisplatin 75 mg/ m^2 as an IV infusion on Day 1 of each 3 week cycle plus MK-1775 200 mg single dose orally, on Day 2 of each cycle. | Participants received carboplatin at an area under the time curve concentration of 5 mg/min/ml (AUC5) as an IV infusion on Day 1 of each 3 week cycle plus MK-1775 100 mg single dose orally, on Day 2 of each cycle. | Participants received carboplatin AUC5 as an IV infusion on Day 1 of each 3 week cycle plus MK-1775 200 mg single dose orally, on Day 2 of each cycle. | Participants received carboplatin AUC5 as an IV infusion on Day 1 of each 3 week cycle plus MK-1775 325 mg single dose orally, on Day 2 of each cycle. | Participants received gemcitabine 1000 mg/m^2 as an IV infusion on Days 1, 8, and 15 of each 4-week cycle plus MK-1775 25 mg orally twice daily (BID) for 2.5 days, starting concomitantly with the IV infusion of gemcitabine on Day 1 and followed by 4 additional doses of MK-1775 25 mg at approximately 12 hour intervals on Days 1-3, 8-9, and 15-17 of each cycle. | Participants received gemcitabine 1000 mg/m^2 as an IV infusion on Days 1, 8, and 15 of each 4 week cycle plus MK-1775 50 mg orally BID for 2.5 days, starting concomitantly with the IV infusion of gemcitabine on Day 1 and followed by 4 doses of MK-1775 25 mg at approximately 12 hour intervals on Days 1-3, 8-9, and 15-17 of each 4 week cycle. | Participants received gemcitabine 1000 mg/m^2 as an IV infusion given once weekly for 3 consecutive weeks of a 4 week cycle plus MK-1775 50 mg orally BID for 2.5 days, starting concomitantly with the IV infusion of gemcitabine on Day 1 and followed by 4 additional doses of MK-1775 50 mg at approximately 12 hour intervals on Days 1-3, 8-9, and 15-17 of each 4 week cycle. | Participants received gemcitabine 1000 mg/m^2 as an IV infusion on Days 1, 8, and 15 of each 4 week cycle plus MK-1775 100 mg orally once daily (QD) on Days 1, 2, 8, 9, 15, and 16 of each 4 week cycle. | Participants received gemcitabine 1000 mg/m^2 as an IV infusion on Days 1, 8, and 15 of each 4 week cycle plus MK-1775 125 mg orally QD on Days 1, 2, 8, 9, 15, and 16 of each 4 week cycle. | Participants received gemcitabine 1000 mg/m^2 as an IV infusion on Days 1, 8, and 15 of each 4 week cycle plus MK-1775 150 mg orally QD on Days 1, 2, 8, 9, 15, and 16 of each 4 week cycle. | Participants received gemcitabine 1000 mg/m^2 as an IV infusion given on Days 1, 8, and 15 of each 4 week cycle plus MK-1775 175 mg orally QD on Days 1, 2, 8, 9, 15, and 16 of each 4 week cycle. | Participants received gemcitabine 1000 mg/m^2 as an IV infusion on Days 1, 8, and 15 of each 4 week cycle plus MK-1775 200 mg orally QD on Days 1, 2, 8, 9, 15, and 16 of each 4 week cycle. | Participants received cisplatin 75 mg/ m^2 as an IV infusion on Day 1 of each 3 week cycle plus MK-1775 50 mg orally BID for 2.5 days, starting concomitantly with the administration of cisplatin on Day 1 and then at 12 hour intervals on Days 1-3 of each 3 week cycle. | Participants received cisplatin 75 mg/ m^2 as an IV infusion on Day 1 of each 3 week cycle plus MK-1775 100 mg orally BID for 2.5 days, starting concomitantly with the administration of cisplatin on Day 1 and then at 12 hour intervals on Days 1-3 of each 3 week cycle. | Participants received cisplatin 75 mg/ m^2 as an IV infusion on Day 1 of each 3 week cycle plus MK-1775 125 mg orally BID for 2.5 days, starting concomitantly with the administration of cisplatin on Day 1 and then at 12 hour intervals on Days 1-3 of each 3 week cycle. | Participants received cisplatin 75 mg/ m^2 as an IV infusion on Day 1 of each 3 week cycle plus MK-1775 150 mg orally BID for 2.5 days, starting concomitantly with the administration of cisplatin on Day 1 and then at 12 hour intervals on Days 1-3 of each 3 week cycle. | Participants received cisplatin 75 mg/ m^2 as an IV infusion on Day 1 of each 3 week cycle plus MK-1775 200 mg orally BID for 2.5 days, starting concomitantly with the administration of cisplatin on Day 1 and then at 12 hour intervals on Days 1-3 of each 3 week cycle. | Participants received cisplatin 75 mg/ m^2 as an IV infusion on Day 1 of each 3 week cycle plus MK-1775 250 mg orally BID for 2.5 days, starting concomitantly with the administration of cisplatin on Day 1 and then at 12 hour intervals on Days 1-3 of each 3 week cycle. | Participants received carboplatin AUC 5 as an IV infusion on Day 1 of each 3 week cycle plus MK-1775 75 mg orally BID for 2.5 days, starting concomitantly with the administration of carboplatin on Day 1 and then at 12 hour intervals on Days 1-3 of each 3 week cycle. | Participants received carboplatin AUC 5 as an IV infusion on Day 1 of each 3 week cycle plus MK-1775 150 mg orally BID for 2.5 days, starting concomitantly with the administration of carboplatin on Day 1 and then at 12 hour intervals on Days 1-3 of each 3 week cycle. | Participants received carboplatin AUC 5 as an IV infusion on Day 1 of each 3 week cycle plus MK-1775 225 mg orally BID for 2.5 days, starting concomitantly with the administration of carboplatin on Day 1 and then at 12 hour intervals on Days 1-3 of each 3 week cycle. | Participants received carboplatin AUC 5 as an IV infusion on Day 1 of each 3 week cycle plus MK-1775 325 mg orally BID for 2.5 days, starting concomitantly with the administration of carboplatin on Day 1 and then at 12 hour intervals on Days 1-3 of each 3 week cycle. |
| Measure Participants | 3 | 3 | 3 | 6 | 8 | 3 | 10 | 3 | 4 | 9 | 6 | 13 | 6 | 5 | 4 | 11 | 16 | 6 | 4 | 7 | 6 | 10 | 14 | 4 | 4 | 4 | 26 | 12 |
| Count of Participants [Participants] |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
2
22.2%
|
0
0%
|
2
20%
|
0
0%
|
0
0%
|
0
0%
|
1
16.7%
|
2
15.4%
|
5
83.3%
|
0
0%
|
0
0%
|
2
18.2%
|
1
6.3%
|
3
50%
|
0
0%
|
1
14.3%
|
0
0%
|
0
0%
|
4
28.6%
|
3
75%
|
0
0%
|
0
0%
|
7
26.9%
|
6
50%
|
| Title | Percentage of Total Cyclin-dependent Kinase (CDC2)-Positive Cells That Were Phosphorylated (pCDC2) in Skin Cells at Baseline and 8 Hours After MK-1775 Dosing |
|---|---|
| Description | The pCDC2 level in skin cells was used as a marker to evaluate MK-1775 activity. Analysis was done by immunohistochemistry and the percentage of total CDC2-positive cells that were pCDC2 positive (% pCDC2-positive cells) at baseline and 8 hours after MK-1775 dosing were reported for participants in Part 1, 2-A, and 2-B/3 treatment groups with available data per protocol. |
| Time Frame | Baseline, 8 hours after first MK-1775 dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants in Parts 1, 2-A, and 2-B/3 with ≥1 dose treatment and evaluable CDC2 data at 8 hours post dosing. Per protocol the MK-1775 QD x2.5 Multi Dose + Gemcitabine groups, MK-1775 150, 200, and 250 mg BID x 2.5 Multi Dose + cisplatin 75 mg/m^2 groups, and MK-1775 325 mg BID x 2.5 Multi Dose + carboplatin AUC 5 group did not have data reported |
| Arm/Group Title | MK-1775 325 mg Single Dose | MK-1775 650 mg Single Dose | MK-1775 1300 mg Single Dose | MK-1775 100 mg Single Dose + Gemcitabine 1000 mg/m^2 | MK-1775 200 mg Single Dose + Gemcitabine 1000 mg/m^2 | MK-1775 100 mg Single Dose + Cisplatin 75 mg/ m^2 | MK-1775 200 mg Single Dose + Cisplatin 75 mg/ m^2 | MK-1775 100 mg Single Dose + Carboplatin AUC 5 | MK-1775 200 mg Single Dose + Carboplatin AUC 5 | MK-1775 325 mg Single Dose + Carboplatin AUC 5 | MK-1775 25 mg BID x2.5 Multi Dose + Gemcitabine 1000 mg/ m^2 | MK-1775 50/25 mg BID x2.5 Multi + Gemcitabine 1000 mg/ m^2 | MK-1775 50 mg BID x2.5 Multi + Gemcitabine 1000 mg/ m^2 | MK-1775 100 mg QD x2 Multi + Gemcitabine 1000 mg/ m^2 | MK-1775 125 mg QD x2 Multi + Gemcitabine 1000 mg/ m^2 | MK-1775 150 mg QD x2 Multi + Gemcitabine 1000 mg/ m^2 | MK-1775 175 mg QD x2 Multi Dose + Gemcitabine 1000 mg/ m^2 | MK-1775 200 mg QD x2 Multi Dose + Gemcitabine 1000 mg/ m^2 | MK-1775 50 mg BID x2.5 Multi Dose + Cisplatin 75 mg/ m^2 | MK-1775 100 mg BID x2.5 Multi Dose + Cisplatin 75 mg/ m^2 | MK-1775 125 mg BID x2.5 Multi Dose + Cisplatin 75 mg/ m^2 | MK-1775 150 mg BID x2.5 Multi Dose + Cisplatin 75 mg/ m^2 | MK-1775 200 mg BID x2.5 Multi Dose + Cisplatin 75 mg/ m^2 | MK-1775 250 mg BID x2.5 Multi Dose + Cisplatin 75 mg/ m^2 | MK-1775 75 mg BID x2.5 Multi Dose + Carboplatin AUC 5 | MK-1775 150 mg BID x 2.5 Multi Dose + Carboplatin AUC 5 | MK-1775 225 mg BID x2.5 Multi Dose + Carboplatin AUC 5 | MK-1775 325 mg BID x2.5 Multi Dose + Carboplatin AUC 5 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants received MK-1775 325 mg, orally, on Day 1. | Participants received MK-1775 650 mg, orally, on Day 1. | Participants received MK-1775 1300 mg, orally, on Day 1. | Participants received gemcitabine 1000 mg/m^2 as an intravenous (IV) infusion on Days 1, 8, and 15 in each 4-week cycle plus MK-1775 100 mg single dose, orally, on Day 2 of each cycle. | Participants received gemcitabine 1000 mg/m^2 as an IV infusion on Days 1, 8, and 15 in each 4-week cycle plus MK-1775 200 mg single dose, orally, on Day 2 of each cycle. | Participants received cisplatin 75 mg/ m^2 as an IV infusion on Day 1 of each 3 week cycle plus MK-1775 100 mg single dose orally, on Day 2 of each cycle. | Participants received cisplatin 75 mg/ m^2 as an IV infusion on Day 1 of each 3 week cycle plus MK-1775 200 mg single dose orally, on Day 2 of each cycle. | Participants received carboplatin at an area under the time curve concentration of 5 mg/min/ml (AUC5) as an IV infusion on Day 1 of each 3 week cycle plus MK-1775 100 mg single dose orally, on Day 2 of each cycle. | Participants received carboplatin AUC5 as an IV infusion on Day 1 of each 3 week cycle plus MK-1775 200 mg single dose orally, on Day 2 of each cycle. | Participants received carboplatin AUC5 as an IV infusion on Day 1 of each 3 week cycle plus MK-1775 325 mg single dose orally, on Day 2 of each cycle. | Participants received gemcitabine 1000 mg/m^2 as an IV infusion on Days 1, 8, and 15 of each 4-week cycle plus MK-1775 25 mg orally twice daily (BID) for 2.5 days, starting concomitantly with the IV infusion of gemcitabine on Day 1 and followed by 4 additional doses of MK-1775 25 mg at approximately 12 hour intervals on Days 1-3, 8-9, and 15-17 of each cycle. | Participants received gemcitabine 1000 mg/m^2 as an IV infusion on Days 1, 8, and 15 of each 4 week cycle plus MK-1775 50 mg orally BID for 2.5 days, starting concomitantly with the IV infusion of gemcitabine on Day 1 and followed by 4 doses of MK-1775 25 mg at approximately 12 hour intervals on Days 1-3, 8-9, and 15-17 of each 4 week cycle. | Participants received gemcitabine 1000 mg/m^2 as an IV infusion given once weekly for 3 consecutive weeks of a 4 week cycle plus MK-1775 50 mg orally BID for 2.5 days, starting concomitantly with the IV infusion of gemcitabine on Day 1 and followed by 4 additional doses of MK-1775 50 mg at approximately 12 hour intervals on Days 1-3, 8-9, and 15-17 of each 4 week cycle. | Participants received gemcitabine 1000 mg/m^2 as an IV infusion on Days 1, 8, and 15 of each 4 week cycle plus MK-1775 100 mg orally once daily (QD) on Days 1, 2, 8, 9, 15, and 16 of each 4 week cycle. | Participants received gemcitabine 1000 mg/m^2 as an IV infusion on Days 1, 8, and 15 of each 4 week cycle plus MK-1775 125 mg orally QD on Days 1, 2, 8, 9, 15, and 16 of each 4 week cycle. | Participants received gemcitabine 1000 mg/m^2 as an IV infusion on Days 1, 8, and 15 of each 4 week cycle plus MK-1775 150 mg orally QD on Days 1, 2, 8, 9, 15, and 16 of each 4 week cycle. | Participants received gemcitabine 1000 mg/m^2 as an IV infusion given on Days 1, 8, and 15 of each 4 week cycle plus MK-1775 175 mg orally QD on Days 1, 2, 8, 9, 15, and 16 of each 4 week cycle. | Participants received gemcitabine 1000 mg/m^2 as an IV infusion on Days 1, 8, and 15 of each 4 week cycle plus MK-1775 200 mg orally QD on Days 1, 2, 8, 9, 15, and 16 of each 4 week cycle. | Participants received cisplatin 75 mg/ m^2 as an IV infusion on Day 1 of each 3 week cycle plus MK-1775 50 mg orally BID for 2.5 days, starting concomitantly with the administration of cisplatin on Day 1 and then at 12 hour intervals on Days 1-3 of each 3 week cycle. | Participants received cisplatin 75 mg/ m^2 as an IV infusion on Day 1 of each 3 week cycle plus MK-1775 100 mg orally BID for 2.5 days, starting concomitantly with the administration of cisplatin on Day 1 and then at 12 hour intervals on Days 1-3 of each 3 week cycle. | Participants received cisplatin 75 mg/ m^2 as an IV infusion on Day 1 of each 3 week cycle plus MK-1775 125 mg orally BID for 2.5 days, starting concomitantly with the administration of cisplatin on Day 1 and then at 12 hour intervals on Days 1-3 of each 3 week cycle. | Participants received cisplatin 75 mg/ m^2 as an IV infusion on Day 1 of each 3 week cycle plus MK-1775 150 mg orally BID for 2.5 days, starting concomitantly with the administration of cisplatin on Day 1 and then at 12 hour intervals on Days 1-3 of each 3 week cycle. | Participants received cisplatin 75 mg/ m^2 as an IV infusion on Day 1 of each 3 week cycle plus MK-1775 200 mg orally BID for 2.5 days, starting concomitantly with the administration of cisplatin on Day 1 and then at 12 hour intervals on Days 1-3 of each 3 week cycle. | Participants received cisplatin 75 mg/ m^2 as an IV infusion on Day 1 of each 3 week cycle plus MK-1775 250 mg orally BID for 2.5 days, starting concomitantly with the administration of cisplatin on Day 1 and then at 12 hour intervals on Days 1-3 of each 3 week cycle. | Participants received carboplatin AUC 5 as an IV infusion on Day 1 of each 3 week cycle plus MK-1775 75 mg orally BID for 2.5 days, starting concomitantly with the administration of carboplatin on Day 1 and then at 12 hour intervals on Days 1-3 of each 3 week cycle. | Participants received carboplatin AUC 5 as an IV infusion on Day 1 of each 3 week cycle plus MK-1775 150 mg orally BID for 2.5 days, starting concomitantly with the administration of carboplatin on Day 1 and then at 12 hour intervals on Days 1-3 of each 3 week cycle. | Participants received carboplatin AUC 5 as an IV infusion on Day 1 of each 3 week cycle plus MK-1775 225 mg orally BID for 2.5 days, starting concomitantly with the administration of carboplatin on Day 1 and then at 12 hour intervals on Days 1-3 of each 3 week cycle. | Participants received carboplatin AUC 5 as an IV infusion on Day 1 of each 3 week cycle plus MK-1775 325 mg orally BID for 2.5 days, starting concomitantly with the administration of carboplatin on Day 1 and then at 12 hour intervals on Days 1-3 of each 3 week cycle. |
| Measure Participants | 3 | 3 | 3 | 4 | 7 | 1 | 9 | 1 | 3 | 8 | 6 | 6 | 6 | 0 | 0 | 0 | 0 | 0 | 3 | 7 | 1 | 0 | 0 | 0 | 4 | 4 | 8 | 0 |
| Baseline percentage |
40.8
|
35.1
|
36.2
|
53.2
|
40.7
|
16.1
|
28.6
|
34.4
|
17.6
|
22.4
|
28.1
|
18.3
|
30.8
|
16.4
|
24.1
|
21.4
|
15.7
|
27
|
21
|
|||||||||
| Percentage after dosing |
18
|
13.4
|
20.6
|
28.9
|
35.7
|
14.8
|
22.1
|
41.9
|
20.9
|
17.1
|
20.1
|
13.7
|
16.6
|
17.8
|
14.4
|
19.9
|
12.1
|
16.8
|
11.5
|
| Title | Percentage of Total pCDC2 in Skin Cells at Baseline and 24 Hours After MK-1775 Dosing |
|---|---|
| Description | The pCDC2 level in skin cells was used as a marker to evaluate MK-1775 activity. Analysis was done by immunohistochemistry and the percentage of total pCDC2 at baseline and 24 hours after MK-1775 dosing were reported for participants in the Part 2-B/3 MK-1775 QD x2 Multi Dose plus Gemcitabine treatment groups with available data per protocol. |
| Time Frame | Baseline, 24 hours after first MK-1775 dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants in the Part 2-B/3 MK-1775 QD x2 Multi Dose plus Gemcitabine treatment groups who received at least one dose of study treatment and had evaluable CDC2 data at 24 hours post dosing. Per protocol, the Part 1, Part 2-A, and Part 2-B/3 MK-1775 BID treatment groups did not have data reported for this time point. |
| Arm/Group Title | MK-1775 325 mg Single Dose | MK-1775 650 mg Single Dose | MK-1775 1300 mg Single Dose | MK-1775 100 mg Single Dose + Gemcitabine 1000 mg/m^2 | MK-1775 200 mg Single Dose + Gemcitabine 1000 mg/m^2 | MK-1775 100 mg Single Dose + Cisplatin 75 mg/ m^2 | MK-1775 200 mg Single Dose + Cisplatin 75 mg/ m^2 | MK-1775 100 mg Single Dose + Carboplatin AUC 5 | MK-1775 200 mg Single Dose + Carboplatin AUC 5 | MK-1775 325 mg Single Dose + Carboplatin AUC 5 | MK-1775 25 mg BID x2.5 Multi Dose + Gemcitabine 1000 mg/ m^2 | MK-1775 50/25 mg BID x2.5 Multi + Gemcitabine 1000 mg/ m^2 | MK-1775 50 mg BID x2.5 Multi + Gemcitabine 1000 mg/ m^2 | MK-1775 100 mg QD x2 Multi + Gemcitabine 1000 mg/ m^2 | MK-1775 125 mg QD x2 Multi + Gemcitabine 1000 mg/ m^2 | MK-1775 150 mg QD x2 Multi + Gemcitabine 1000 mg/ m^2 | MK-1775 175 mg QD x2 Multi Dose + Gemcitabine 1000 mg/ m^2 | MK-1775 200 mg QD x2 Multi Dose + Gemcitabine 1000 mg/ m^2 | MK-1775 50 mg BID x2.5 Multi Dose + Cisplatin 75 mg/ m^2 | MK-1775 100 mg BID x2.5 Multi Dose + Cisplatin 75 mg/ m^2 | MK-1775 125 mg BID x2.5 Multi Dose + Cisplatin 75 mg/ m^2 | MK-1775 150 mg BID x2.5 Multi Dose + Cisplatin 75 mg/ m^2 | MK-1775 200 mg BID x2.5 Multi Dose + Cisplatin 75 mg/ m^2 | MK-1775 250 mg BID x2.5 Multi Dose + Cisplatin 75 mg/ m^2 | MK-1775 75 mg BID x2.5 Multi Dose + Carboplatin AUC 5 | MK-1775 150 mg BID x 2.5 Multi Dose + Carboplatin AUC 5 | MK-1775 225 mg BID x2.5 Multi Dose + Carboplatin AUC 5 | MK-1775 325 mg BID x2.5 Multi Dose + Carboplatin AUC 5 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants received MK-1775 325 mg, orally, on Day 1. | Participants received MK-1775 650 mg, orally, on Day 1. | Participants received MK-1775 1300 mg, orally, on Day 1. | Participants received gemcitabine 1000 mg/m^2 as an intravenous (IV) infusion on Days 1, 8, and 15 in each 4-week cycle plus MK-1775 100 mg single dose, orally, on Day 2 of each cycle. | Participants received gemcitabine 1000 mg/m^2 as an IV infusion on Days 1, 8, and 15 in each 4-week cycle plus MK-1775 200 mg single dose, orally, on Day 2 of each cycle. | Participants received cisplatin 75 mg/ m^2 as an IV infusion on Day 1 of each 3 week cycle plus MK-1775 100 mg single dose orally, on Day 2 of each cycle. | Participants received cisplatin 75 mg/ m^2 as an IV infusion on Day 1 of each 3 week cycle plus MK-1775 200 mg single dose orally, on Day 2 of each cycle. | Participants received carboplatin at an area under the time curve concentration of 5 mg/min/ml (AUC5) as an IV infusion on Day 1 of each 3 week cycle plus MK-1775 100 mg single dose orally, on Day 2 of each cycle. | Participants received carboplatin AUC5 as an IV infusion on Day 1 of each 3 week cycle plus MK-1775 200 mg single dose orally, on Day 2 of each cycle. | Participants received carboplatin AUC5 as an IV infusion on Day 1 of each 3 week cycle plus MK-1775 325 mg single dose orally, on Day 2 of each cycle. | Participants received gemcitabine 1000 mg/m^2 as an IV infusion on Days 1, 8, and 15 of each 4-week cycle plus MK-1775 25 mg orally twice daily (BID) for 2.5 days, starting concomitantly with the IV infusion of gemcitabine on Day 1 and followed by 4 additional doses of MK-1775 25 mg at approximately 12 hour intervals on Days 1-3, 8-9, and 15-17 of each cycle. | Participants received gemcitabine 1000 mg/m^2 as an IV infusion on Days 1, 8, and 15 of each 4 week cycle plus MK-1775 50 mg orally BID for 2.5 days, starting concomitantly with the IV infusion of gemcitabine on Day 1 and followed by 4 doses of MK-1775 25 mg at approximately 12 hour intervals on Days 1-3, 8-9, and 15-17 of each 4 week cycle. | Participants received gemcitabine 1000 mg/m^2 as an IV infusion given once weekly for 3 consecutive weeks of a 4 week cycle plus MK-1775 50 mg orally BID for 2.5 days, starting concomitantly with the IV infusion of gemcitabine on Day 1 and followed by 4 additional doses of MK-1775 50 mg at approximately 12 hour intervals on Days 1-3, 8-9, and 15-17 of each 4 week cycle. | Participants received gemcitabine 1000 mg/m^2 as an IV infusion on Days 1, 8, and 15 of each 4 week cycle plus MK-1775 100 mg orally once daily (QD) on Days 1, 2, 8, 9, 15, and 16 of each 4 week cycle. | Participants received gemcitabine 1000 mg/m^2 as an IV infusion on Days 1, 8, and 15 of each 4 week cycle plus MK-1775 125 mg orally QD on Days 1, 2, 8, 9, 15, and 16 of each 4 week cycle. | Participants received gemcitabine 1000 mg/m^2 as an IV infusion on Days 1, 8, and 15 of each 4 week cycle plus MK-1775 150 mg orally QD on Days 1, 2, 8, 9, 15, and 16 of each 4 week cycle. | Participants received gemcitabine 1000 mg/m^2 as an IV infusion given on Days 1, 8, and 15 of each 4 week cycle plus MK-1775 175 mg orally QD on Days 1, 2, 8, 9, 15, and 16 of each 4 week cycle. | Participants received gemcitabine 1000 mg/m^2 as an IV infusion on Days 1, 8, and 15 of each 4 week cycle plus MK-1775 200 mg orally QD on Days 1, 2, 8, 9, 15, and 16 of each 4 week cycle. | Participants received cisplatin 75 mg/ m^2 as an IV infusion on Day 1 of each 3 week cycle plus MK-1775 50 mg orally BID for 2.5 days, starting concomitantly with the administration of cisplatin on Day 1 and then at 12 hour intervals on Days 1-3 of each 3 week cycle. | Participants received cisplatin 75 mg/ m^2 as an IV infusion on Day 1 of each 3 week cycle plus MK-1775 100 mg orally BID for 2.5 days, starting concomitantly with the administration of cisplatin on Day 1 and then at 12 hour intervals on Days 1-3 of each 3 week cycle. | Participants received cisplatin 75 mg/ m^2 as an IV infusion on Day 1 of each 3 week cycle plus MK-1775 125 mg orally BID for 2.5 days, starting concomitantly with the administration of cisplatin on Day 1 and then at 12 hour intervals on Days 1-3 of each 3 week cycle. | Participants received cisplatin 75 mg/ m^2 as an IV infusion on Day 1 of each 3 week cycle plus MK-1775 150 mg orally BID for 2.5 days, starting concomitantly with the administration of cisplatin on Day 1 and then at 12 hour intervals on Days 1-3 of each 3 week cycle. | Participants received cisplatin 75 mg/ m^2 as an IV infusion on Day 1 of each 3 week cycle plus MK-1775 200 mg orally BID for 2.5 days, starting concomitantly with the administration of cisplatin on Day 1 and then at 12 hour intervals on Days 1-3 of each 3 week cycle. | Participants received cisplatin 75 mg/ m^2 as an IV infusion on Day 1 of each 3 week cycle plus MK-1775 250 mg orally BID for 2.5 days, starting concomitantly with the administration of cisplatin on Day 1 and then at 12 hour intervals on Days 1-3 of each 3 week cycle. | Participants received carboplatin AUC 5 as an IV infusion on Day 1 of each 3 week cycle plus MK-1775 75 mg orally BID for 2.5 days, starting concomitantly with the administration of carboplatin on Day 1 and then at 12 hour intervals on Days 1-3 of each 3 week cycle. | Participants received carboplatin AUC 5 as an IV infusion on Day 1 of each 3 week cycle plus MK-1775 150 mg orally BID for 2.5 days, starting concomitantly with the administration of carboplatin on Day 1 and then at 12 hour intervals on Days 1-3 of each 3 week cycle. | Participants received carboplatin AUC 5 as an IV infusion on Day 1 of each 3 week cycle plus MK-1775 225 mg orally BID for 2.5 days, starting concomitantly with the administration of carboplatin on Day 1 and then at 12 hour intervals on Days 1-3 of each 3 week cycle. | Participants received carboplatin AUC 5 as an IV infusion on Day 1 of each 3 week cycle plus MK-1775 325 mg orally BID for 2.5 days, starting concomitantly with the administration of carboplatin on Day 1 and then at 12 hour intervals on Days 1-3 of each 3 week cycle. |
| Measure Participants | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 4 | 4 | 11 | 0 | 4 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Baseline percentage |
47.5
|
27.9
|
18.7
|
11.6
|
||||||||||||||||||||||||
| Percentage after dosing |
29.9
|
17.7
|
12.7
|
6.3
|
| Title | Percentage of Total pCDC2 in Skin Cells at Baseline and 48 Hours After MK-1775 Dosing |
|---|---|
| Description | The pCDC2 level in skin cells was used as a marker to evaluate MK-1775 activity. Analysis was done by immunohistochemistry and the percentage of total pCDC2 at baseline and at 48 hours after MK-1775 dosing were reported for participants in the Part 2-B/3 MK-1775 (150 mg, 200 mg, 250) BID x 2.5 Multi Dose plus cisplatin 75 mg/m^2 groups and the 325 mg BID x2.5 Multi Dose + Carboplatin group with available data per protocol. |
| Time Frame | Baseline, 48 hours after first MK-1775 dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants in Part 2-B/3 MK-1775 (150 mg, 200 mg, 250) BID x 2.5 Multi Dose plus cisplatin 75 mg/m^2 groups and 325 mg BID x2.5 Multi Dose + carboplatin group who received ≥1 dose of study treatment and had evaluable CDC2 data at 48 hours post dose. Per protocol, Part 1, Part 2-A, and remaining Part 2-B/3 groups did not have data reported. |
| Arm/Group Title | MK-1775 325 mg Single Dose | MK-1775 650 mg Single Dose | MK-1775 1300 mg Single Dose | MK-1775 100 mg Single Dose + Gemcitabine 1000 mg/m^2 | MK-1775 200 mg Single Dose + Gemcitabine 1000 mg/m^2 | MK-1775 100 mg Single Dose + Cisplatin 75 mg/ m^2 | MK-1775 200 mg Single Dose + Cisplatin 75 mg/ m^2 | MK-1775 100 mg Single Dose + Carboplatin AUC 5 | MK-1775 200 mg Single Dose + Carboplatin AUC 5 | MK-1775 325 mg Single Dose + Carboplatin AUC 5 | MK-1775 25 mg BID x2.5 Multi Dose + Gemcitabine 1000 mg/ m^2 | MK-1775 50/25 mg BID x2.5 Multi + Gemcitabine 1000 mg/ m^2 | MK-1775 50 mg BID x2.5 Multi + Gemcitabine 1000 mg/ m^2 | MK-1775 100 mg QD x2 Multi + Gemcitabine 1000 mg/ m^2 | MK-1775 125 mg QD x2 Multi + Gemcitabine 1000 mg/ m^2 | MK-1775 150 mg QD x2 Multi + Gemcitabine 1000 mg/ m^2 | MK-1775 175 mg QD x2 Multi Dose + Gemcitabine 1000 mg/ m^2 | MK-1775 200 mg QD x2 Multi Dose + Gemcitabine 1000 mg/ m^2 | MK-1775 50 mg BID x2.5 Multi Dose + Cisplatin 75 mg/ m^2 | MK-1775 100 mg BID x2.5 Multi Dose + Cisplatin 75 mg/ m^2 | MK-1775 125 mg BID x2.5 Multi Dose + Cisplatin 75 mg/ m^2 | MK-1775 150 mg BID x2.5 Multi Dose + Cisplatin 75 mg/ m^2 | MK-1775 200 mg BID x2.5 Multi Dose + Cisplatin 75 mg/ m^2 | MK-1775 250 mg BID x2.5 Multi Dose + Cisplatin 75 mg/ m^2 | MK-1775 75 mg BID x2.5 Multi Dose + Carboplatin AUC 5 | MK-1775 150 mg BID x 2.5 Multi Dose + Carboplatin AUC 5 | MK-1775 225 mg BID x2.5 Multi Dose + Carboplatin AUC 5 | MK-1775 325 mg BID x2.5 Multi Dose + Carboplatin AUC 5 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants received MK-1775 325 mg, orally, on Day 1. | Participants received MK-1775 650 mg, orally, on Day 1. | Participants received MK-1775 1300 mg, orally, on Day 1. | Participants received gemcitabine 1000 mg/m^2 as an intravenous (IV) infusion on Days 1, 8, and 15 in each 4-week cycle plus MK-1775 100 mg single dose, orally, on Day 2 of each cycle. | Participants received gemcitabine 1000 mg/m^2 as an IV infusion on Days 1, 8, and 15 in each 4-week cycle plus MK-1775 200 mg single dose, orally, on Day 2 of each cycle. | Participants received cisplatin 75 mg/ m^2 as an IV infusion on Day 1 of each 3 week cycle plus MK-1775 100 mg single dose orally, on Day 2 of each cycle. | Participants received cisplatin 75 mg/ m^2 as an IV infusion on Day 1 of each 3 week cycle plus MK-1775 200 mg single dose orally, on Day 2 of each cycle. | Participants received carboplatin at an area under the time curve concentration of 5 mg/min/ml (AUC5) as an IV infusion on Day 1 of each 3 week cycle plus MK-1775 100 mg single dose orally, on Day 2 of each cycle. | Participants received carboplatin AUC5 as an IV infusion on Day 1 of each 3 week cycle plus MK-1775 200 mg single dose orally, on Day 2 of each cycle. | Participants received carboplatin AUC5 as an IV infusion on Day 1 of each 3 week cycle plus MK-1775 325 mg single dose orally, on Day 2 of each cycle. | Participants received gemcitabine 1000 mg/m^2 as an IV infusion on Days 1, 8, and 15 of each 4-week cycle plus MK-1775 25 mg orally twice daily (BID) for 2.5 days, starting concomitantly with the IV infusion of gemcitabine on Day 1 and followed by 4 additional doses of MK-1775 25 mg at approximately 12 hour intervals on Days 1-3, 8-9, and 15-17 of each cycle. | Participants received gemcitabine 1000 mg/m^2 as an IV infusion on Days 1, 8, and 15 of each 4 week cycle plus MK-1775 50 mg orally BID for 2.5 days, starting concomitantly with the IV infusion of gemcitabine on Day 1 and followed by 4 doses of MK-1775 25 mg at approximately 12 hour intervals on Days 1-3, 8-9, and 15-17 of each 4 week cycle. | Participants received gemcitabine 1000 mg/m^2 as an IV infusion given once weekly for 3 consecutive weeks of a 4 week cycle plus MK-1775 50 mg orally BID for 2.5 days, starting concomitantly with the IV infusion of gemcitabine on Day 1 and followed by 4 additional doses of MK-1775 50 mg at approximately 12 hour intervals on Days 1-3, 8-9, and 15-17 of each 4 week cycle. | Participants received gemcitabine 1000 mg/m^2 as an IV infusion on Days 1, 8, and 15 of each 4 week cycle plus MK-1775 100 mg orally once daily (QD) on Days 1, 2, 8, 9, 15, and 16 of each 4 week cycle. | Participants received gemcitabine 1000 mg/m^2 as an IV infusion on Days 1, 8, and 15 of each 4 week cycle plus MK-1775 125 mg orally QD on Days 1, 2, 8, 9, 15, and 16 of each 4 week cycle. | Participants received gemcitabine 1000 mg/m^2 as an IV infusion on Days 1, 8, and 15 of each 4 week cycle plus MK-1775 150 mg orally QD on Days 1, 2, 8, 9, 15, and 16 of each 4 week cycle. | Participants received gemcitabine 1000 mg/m^2 as an IV infusion given on Days 1, 8, and 15 of each 4 week cycle plus MK-1775 175 mg orally QD on Days 1, 2, 8, 9, 15, and 16 of each 4 week cycle. | Participants received gemcitabine 1000 mg/m^2 as an IV infusion on Days 1, 8, and 15 of each 4 week cycle plus MK-1775 200 mg orally QD on Days 1, 2, 8, 9, 15, and 16 of each 4 week cycle. | Participants received cisplatin 75 mg/ m^2 as an IV infusion on Day 1 of each 3 week cycle plus MK-1775 50 mg orally BID for 2.5 days, starting concomitantly with the administration of cisplatin on Day 1 and then at 12 hour intervals on Days 1-3 of each 3 week cycle. | Participants received cisplatin 75 mg/ m^2 as an IV infusion on Day 1 of each 3 week cycle plus MK-1775 100 mg orally BID for 2.5 days, starting concomitantly with the administration of cisplatin on Day 1 and then at 12 hour intervals on Days 1-3 of each 3 week cycle. | Participants received cisplatin 75 mg/ m^2 as an IV infusion on Day 1 of each 3 week cycle plus MK-1775 125 mg orally BID for 2.5 days, starting concomitantly with the administration of cisplatin on Day 1 and then at 12 hour intervals on Days 1-3 of each 3 week cycle. | Participants received cisplatin 75 mg/ m^2 as an IV infusion on Day 1 of each 3 week cycle plus MK-1775 150 mg orally BID for 2.5 days, starting concomitantly with the administration of cisplatin on Day 1 and then at 12 hour intervals on Days 1-3 of each 3 week cycle. | Participants received cisplatin 75 mg/ m^2 as an IV infusion on Day 1 of each 3 week cycle plus MK-1775 200 mg orally BID for 2.5 days, starting concomitantly with the administration of cisplatin on Day 1 and then at 12 hour intervals on Days 1-3 of each 3 week cycle. | Participants received cisplatin 75 mg/ m^2 as an IV infusion on Day 1 of each 3 week cycle plus MK-1775 250 mg orally BID for 2.5 days, starting concomitantly with the administration of cisplatin on Day 1 and then at 12 hour intervals on Days 1-3 of each 3 week cycle. | Participants received carboplatin AUC 5 as an IV infusion on Day 1 of each 3 week cycle plus MK-1775 75 mg orally BID for 2.5 days, starting concomitantly with the administration of carboplatin on Day 1 and then at 12 hour intervals on Days 1-3 of each 3 week cycle. | Participants received carboplatin AUC 5 as an IV infusion on Day 1 of each 3 week cycle plus MK-1775 150 mg orally BID for 2.5 days, starting concomitantly with the administration of carboplatin on Day 1 and then at 12 hour intervals on Days 1-3 of each 3 week cycle. | Participants received carboplatin AUC 5 as an IV infusion on Day 1 of each 3 week cycle plus MK-1775 225 mg orally BID for 2.5 days, starting concomitantly with the administration of carboplatin on Day 1 and then at 12 hour intervals on Days 1-3 of each 3 week cycle. | Participants received carboplatin AUC 5 as an IV infusion on Day 1 of each 3 week cycle plus MK-1775 325 mg orally BID for 2.5 days, starting concomitantly with the administration of carboplatin on Day 1 and then at 12 hour intervals on Days 1-3 of each 3 week cycle. |
| Measure Participants | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 8 | 9 | 4 | 0 | 0 | 0 | 9 |
| Baseline percentage |
28.6
|
31.5
|
31.5
|
33.5
|
||||||||||||||||||||||||
| Percentage after dosing |
15.7
|
7.4
|
11.1
|
15.1
|
| Title | Plasma Concentration of MK-1775 at 8 Hours After Administration (C8hr) of Single or Multiple Oral Doses |
|---|---|
| Description | MK-1775 was measured in the plasma at 8 hours after dosing (Day 1 for single dose of monotherapy, Day 2 of single-dose combination therapy and QD x 2 Combination dosing, and Day 3 dose for BID X 2.5 combination dosing) for participants with available data. |
| Time Frame | 8 hours after MK-1775 dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| All treated participants with available C8hr data. |
| Arm/Group Title | MK-1775 325 mg Single Dose | MK-1775 650 mg Single Dose | MK-1775 1300 mg Single Dose | MK-1775 100 mg Single Dose + Gemcitabine 1000 mg/m^2 | MK-1775 200 mg Single Dose + Gemcitabine 1000 mg/m^2 | MK-1775 100 mg Single Dose + Cisplatin 75 mg/ m^2 | MK-1775 200 mg Single Dose + Cisplatin 75 mg/ m^2 | MK-1775 100 mg Single Dose + Carboplatin AUC 5 | MK-1775 200 mg Single Dose + Carboplatin AUC 5 | MK-1775 325 mg Single Dose + Carboplatin AUC 5 | MK-1775 25 mg BID x2.5 Multi Dose + Gemcitabine 1000 mg/ m^2 | MK-1775 50/25 mg BID x2.5 Multi + Gemcitabine 1000 mg/ m^2 | MK-1775 50 mg BID x2.5 Multi + Gemcitabine 1000 mg/ m^2 | MK-1775 100 mg QD x2 Multi + Gemcitabine 1000 mg/ m^2 | MK-1775 125 mg QD x2 Multi + Gemcitabine 1000 mg/ m^2 | MK-1775 150 mg QD x2 Multi + Gemcitabine 1000 mg/ m^2 | MK-1775 175 mg QD x2 Multi Dose + Gemcitabine 1000 mg/ m^2 | MK-1775 200 mg QD x2 Multi Dose + Gemcitabine 1000 mg/ m^2 | MK-1775 50 mg BID x2.5 Multi Dose + Cisplatin 75 mg/ m^2 | MK-1775 100 mg BID x2.5 Multi Dose + Cisplatin 75 mg/ m^2 | MK-1775 125 mg BID x2.5 Multi Dose + Cisplatin 75 mg/ m^2 | MK-1775 150 mg BID x2.5 Multi Dose + Cisplatin 75 mg/ m^2 | MK-1775 200 mg BID x2.5 Multi Dose + Cisplatin 75 mg/ m^2 | MK-1775 250 mg BID x2.5 Multi Dose + Cisplatin 75 mg/ m^2 | MK-1775 75 mg BID x2.5 Multi Dose + Carboplatin AUC 5 | MK-1775 150 mg BID x 2.5 Multi Dose + Carboplatin AUC 5 | MK-1775 225 mg BID x2.5 Multi Dose + Carboplatin AUC 5 | MK-1775 325 mg BID x2.5 Multi Dose + Carboplatin AUC 5 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants received MK-1775 325 mg, orally, on Day 1. | Participants received MK-1775 650 mg, orally, on Day 1. | Participants received MK-1775 1300 mg, orally, on Day 1. | Participants received gemcitabine 1000 mg/m^2 as an intravenous (IV) infusion on Days 1, 8, and 15 in each 4-week cycle plus MK-1775 100 mg single dose, orally, on Day 2 of each cycle. | Participants received gemcitabine 1000 mg/m^2 as an IV infusion on Days 1, 8, and 15 in each 4-week cycle plus MK-1775 200 mg single dose, orally, on Day 2 of each cycle. | Participants received cisplatin 75 mg/ m^2 as an IV infusion on Day 1 of each 3 week cycle plus MK-1775 100 mg single dose orally, on Day 2 of each cycle. | Participants received cisplatin 75 mg/ m^2 as an IV infusion on Day 1 of each 3 week cycle plus MK-1775 200 mg single dose orally, on Day 2 of each cycle. | Participants received carboplatin at an area under the time curve concentration of 5 mg/min/ml (AUC5) as an IV infusion on Day 1 of each 3 week cycle plus MK-1775 100 mg single dose orally, on Day 2 of each cycle. | Participants received carboplatin AUC5 as an IV infusion on Day 1 of each 3 week cycle plus MK-1775 200 mg single dose orally, on Day 2 of each cycle. | Participants received carboplatin AUC5 as an IV infusion on Day 1 of each 3 week cycle plus MK-1775 325 mg single dose orally, on Day 2 of each cycle. | Participants received gemcitabine 1000 mg/m^2 as an IV infusion on Days 1, 8, and 15 of each 4-week cycle plus MK-1775 25 mg orally twice daily (BID) for 2.5 days, starting concomitantly with the IV infusion of gemcitabine on Day 1 and followed by 4 additional doses of MK-1775 25 mg at approximately 12 hour intervals on Days 1-3, 8-9, and 15-17 of each cycle. | Participants received gemcitabine 1000 mg/m^2 as an IV infusion on Days 1, 8, and 15 of each 4 week cycle plus MK-1775 50 mg orally BID for 2.5 days, starting concomitantly with the IV infusion of gemcitabine on Day 1 and followed by 4 doses of MK-1775 25 mg at approximately 12 hour intervals on Days 1-3, 8-9, and 15-17 of each 4 week cycle. | Participants received gemcitabine 1000 mg/m^2 as an IV infusion given once weekly for 3 consecutive weeks of a 4 week cycle plus MK-1775 50 mg orally BID for 2.5 days, starting concomitantly with the IV infusion of gemcitabine on Day 1 and followed by 4 additional doses of MK-1775 50 mg at approximately 12 hour intervals on Days 1-3, 8-9, and 15-17 of each 4 week cycle. | Participants received gemcitabine 1000 mg/m^2 as an IV infusion on Days 1, 8, and 15 of each 4 week cycle plus MK-1775 100 mg orally once daily (QD) on Days 1, 2, 8, 9, 15, and 16 of each 4 week cycle. | Participants received gemcitabine 1000 mg/m^2 as an IV infusion on Days 1, 8, and 15 of each 4 week cycle plus MK-1775 125 mg orally QD on Days 1, 2, 8, 9, 15, and 16 of each 4 week cycle. | Participants received gemcitabine 1000 mg/m^2 as an IV infusion on Days 1, 8, and 15 of each 4 week cycle plus MK-1775 150 mg orally QD on Days 1, 2, 8, 9, 15, and 16 of each 4 week cycle. | Participants received gemcitabine 1000 mg/m^2 as an IV infusion given on Days 1, 8, and 15 of each 4 week cycle plus MK-1775 175 mg orally QD on Days 1, 2, 8, 9, 15, and 16 of each 4 week cycle. | Participants received gemcitabine 1000 mg/m^2 as an IV infusion on Days 1, 8, and 15 of each 4 week cycle plus MK-1775 200 mg orally QD on Days 1, 2, 8, 9, 15, and 16 of each 4 week cycle. | Participants received cisplatin 75 mg/ m^2 as an IV infusion on Day 1 of each 3 week cycle plus MK-1775 50 mg orally BID for 2.5 days, starting concomitantly with the administration of cisplatin on Day 1 and then at 12 hour intervals on Days 1-3 of each 3 week cycle. | Participants received cisplatin 75 mg/ m^2 as an IV infusion on Day 1 of each 3 week cycle plus MK-1775 100 mg orally BID for 2.5 days, starting concomitantly with the administration of cisplatin on Day 1 and then at 12 hour intervals on Days 1-3 of each 3 week cycle. | Participants received cisplatin 75 mg/ m^2 as an IV infusion on Day 1 of each 3 week cycle plus MK-1775 125 mg orally BID for 2.5 days, starting concomitantly with the administration of cisplatin on Day 1 and then at 12 hour intervals on Days 1-3 of each 3 week cycle. | Participants received cisplatin 75 mg/ m^2 as an IV infusion on Day 1 of each 3 week cycle plus MK-1775 150 mg orally BID for 2.5 days, starting concomitantly with the administration of cisplatin on Day 1 and then at 12 hour intervals on Days 1-3 of each 3 week cycle. | Participants received cisplatin 75 mg/ m^2 as an IV infusion on Day 1 of each 3 week cycle plus MK-1775 200 mg orally BID for 2.5 days, starting concomitantly with the administration of cisplatin on Day 1 and then at 12 hour intervals on Days 1-3 of each 3 week cycle. | Participants received cisplatin 75 mg/ m^2 as an IV infusion on Day 1 of each 3 week cycle plus MK-1775 250 mg orally BID for 2.5 days, starting concomitantly with the administration of cisplatin on Day 1 and then at 12 hour intervals on Days 1-3 of each 3 week cycle. | Participants received carboplatin AUC 5 as an IV infusion on Day 1 of each 3 week cycle plus MK-1775 75 mg orally BID for 2.5 days, starting concomitantly with the administration of carboplatin on Day 1 and then at 12 hour intervals on Days 1-3 of each 3 week cycle. | Participants received carboplatin AUC 5 as an IV infusion on Day 1 of each 3 week cycle plus MK-1775 150 mg orally BID for 2.5 days, starting concomitantly with the administration of carboplatin on Day 1 and then at 12 hour intervals on Days 1-3 of each 3 week cycle. | Participants received carboplatin AUC 5 as an IV infusion on Day 1 of each 3 week cycle plus MK-1775 225 mg orally BID for 2.5 days, starting concomitantly with the administration of carboplatin on Day 1 and then at 12 hour intervals on Days 1-3 of each 3 week cycle. | Participants received carboplatin AUC 5 as an IV infusion on Day 1 of each 3 week cycle plus MK-1775 325 mg orally BID for 2.5 days, starting concomitantly with the administration of carboplatin on Day 1 and then at 12 hour intervals on Days 1-3 of each 3 week cycle. |
| Measure Participants | 3 | 3 | 3 | 6 | 7 | 3 | 8 | 2 | 4 | 8 | 6 | 13 | 5 | 4 | 3 | 11 | 11 | 6 | 4 | 7 | 5 | 7 | 10 | 3 | 4 | 4 | 13 | 11 |
| Mean (Standard Deviation) [nM] |
585
(262)
|
1130
(73.2)
|
2190
(791)
|
129
(46.5)
|
235
(136)
|
108
(62.7)
|
310
(168)
|
119
(0.706)
|
262
(52.1)
|
425
(190)
|
41.7
(16.3)
|
65.4
(26.1)
|
138
(38.8)
|
188
(47.6)
|
241
(92.3)
|
355
(230)
|
346
(144)
|
407
(183)
|
113
(97.7)
|
388
(149)
|
748
(234)
|
920
(439)
|
1070
(528)
|
2010
(581)
|
184
(101)
|
295
(161)
|
985
(301)
|
1960
(651)
|
| Title | Mean Urine Excretion of MK-1775 24 Hours After the Day 1 Monotherapy Dose |
|---|---|
| Description | The mean cumulative amount of MK-1775 excreted unchanged in urine after a single oral dose was measured during the initial monotherapy cycle of the study. For this outcome measure, samples were collected and analyzed only for the MK-1775 monotherapy arms of the study at defined intervals after the Day 1 dose of monotherapy. Part 2 MK-1775 combination arms were not sampled per protocol. |
| Time Frame | At 0-4 hours, 4-8 hours, and 12-24 hours post Day 1 dose of monotherapy |
Outcome Measure Data
| Analysis Population Description |
|---|
| All treated Part 1 participants with available urine sample data. |
| Arm/Group Title | MK-1775 325 mg Single Dose | MK-1775 650 mg Single Dose | MK-1775 1300 mg Single Dose | MK-1775 100 mg Single Dose + Gemcitabine 1000 mg/m^2 | MK-1775 200 mg Single Dose + Gemcitabine 1000 mg/m^2 | MK-1775 100 mg Single Dose + Cisplatin 75 mg/ m^2 | MK-1775 200 mg Single Dose + Cisplatin 75 mg/ m^2 | MK-1775 100 mg Single Dose + Carboplatin AUC 5 | MK-1775 200 mg Single Dose + Carboplatin AUC 5 | MK-1775 325 mg Single Dose + Carboplatin AUC 5 | MK-1775 25 mg BID x2.5 Multi Dose + Gemcitabine 1000 mg/ m^2 | MK-1775 50/25 mg BID x2.5 Multi + Gemcitabine 1000 mg/ m^2 | MK-1775 50 mg BID x2.5 Multi + Gemcitabine 1000 mg/ m^2 | MK-1775 100 mg QD x2 Multi + Gemcitabine 1000 mg/ m^2 | MK-1775 125 mg QD x2 Multi + Gemcitabine 1000 mg/ m^2 | MK-1775 150 mg QD x2 Multi + Gemcitabine 1000 mg/ m^2 | MK-1775 175 mg QD x2 Multi Dose + Gemcitabine 1000 mg/ m^2 | MK-1775 200 mg QD x2 Multi Dose + Gemcitabine 1000 mg/ m^2 | MK-1775 50 mg BID x2.5 Multi Dose + Cisplatin 75 mg/ m^2 | MK-1775 100 mg BID x2.5 Multi Dose + Cisplatin 75 mg/ m^2 | MK-1775 125 mg BID x2.5 Multi Dose + Cisplatin 75 mg/ m^2 | MK-1775 150 mg BID x2.5 Multi Dose + Cisplatin 75 mg/ m^2 | MK-1775 200 mg BID x2.5 Multi Dose + Cisplatin 75 mg/ m^2 | MK-1775 250 mg BID x2.5 Multi Dose + Cisplatin 75 mg/ m^2 | MK-1775 75 mg BID x2.5 Multi Dose + Carboplatin AUC 5 | MK-1775 150 mg BID x 2.5 Multi Dose + Carboplatin AUC 5 | MK-1775 225 mg BID x2.5 Multi Dose + Carboplatin AUC 5 | MK-1775 325 mg BID x2.5 Multi Dose + Carboplatin AUC 5 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants received MK-1775 325 mg, orally, on Day 1. | Participants received MK-1775 650 mg, orally, on Day 1. | Participants received MK-1775 1300 mg, orally, on Day 1. | Participants received gemcitabine 1000 mg/m^2 as an intravenous (IV) infusion on Days 1, 8, and 15 in each 4-week cycle plus MK-1775 100 mg single dose, orally, on Day 2 of each cycle. | Participants received gemcitabine 1000 mg/m^2 as an IV infusion on Days 1, 8, and 15 in each 4-week cycle plus MK-1775 200 mg single dose, orally, on Day 2 of each cycle. | Participants received cisplatin 75 mg/ m^2 as an IV infusion on Day 1 of each 3 week cycle plus MK-1775 100 mg single dose orally, on Day 2 of each cycle. | Participants received cisplatin 75 mg/ m^2 as an IV infusion on Day 1 of each 3 week cycle plus MK-1775 200 mg single dose orally, on Day 2 of each cycle. | Participants received carboplatin at an area under the time curve concentration of 5 mg/min/ml (AUC5) as an IV infusion on Day 1 of each 3 week cycle plus MK-1775 100 mg single dose orally, on Day 2 of each cycle. | Participants received carboplatin AUC5 as an IV infusion on Day 1 of each 3 week cycle plus MK-1775 200 mg single dose orally, on Day 2 of each cycle. | Participants received carboplatin AUC5 as an IV infusion on Day 1 of each 3 week cycle plus MK-1775 325 mg single dose orally, on Day 2 of each cycle. | Participants received gemcitabine 1000 mg/m^2 as an IV infusion on Days 1, 8, and 15 of each 4-week cycle plus MK-1775 25 mg orally twice daily (BID) for 2.5 days, starting concomitantly with the IV infusion of gemcitabine on Day 1 and followed by 4 additional doses of MK-1775 25 mg at approximately 12 hour intervals on Days 1-3, 8-9, and 15-17 of each cycle. | Participants received gemcitabine 1000 mg/m^2 as an IV infusion on Days 1, 8, and 15 of each 4 week cycle plus MK-1775 50 mg orally BID for 2.5 days, starting concomitantly with the IV infusion of gemcitabine on Day 1 and followed by 4 doses of MK-1775 25 mg at approximately 12 hour intervals on Days 1-3, 8-9, and 15-17 of each 4 week cycle. | Participants received gemcitabine 1000 mg/m^2 as an IV infusion given once weekly for 3 consecutive weeks of a 4 week cycle plus MK-1775 50 mg orally BID for 2.5 days, starting concomitantly with the IV infusion of gemcitabine on Day 1 and followed by 4 additional doses of MK-1775 50 mg at approximately 12 hour intervals on Days 1-3, 8-9, and 15-17 of each 4 week cycle. | Participants received gemcitabine 1000 mg/m^2 as an IV infusion on Days 1, 8, and 15 of each 4 week cycle plus MK-1775 100 mg orally once daily (QD) on Days 1, 2, 8, 9, 15, and 16 of each 4 week cycle. | Participants received gemcitabine 1000 mg/m^2 as an IV infusion on Days 1, 8, and 15 of each 4 week cycle plus MK-1775 125 mg orally QD on Days 1, 2, 8, 9, 15, and 16 of each 4 week cycle. | Participants received gemcitabine 1000 mg/m^2 as an IV infusion on Days 1, 8, and 15 of each 4 week cycle plus MK-1775 150 mg orally QD on Days 1, 2, 8, 9, 15, and 16 of each 4 week cycle. | Participants received gemcitabine 1000 mg/m^2 as an IV infusion given on Days 1, 8, and 15 of each 4 week cycle plus MK-1775 175 mg orally QD on Days 1, 2, 8, 9, 15, and 16 of each 4 week cycle. | Participants received gemcitabine 1000 mg/m^2 as an IV infusion on Days 1, 8, and 15 of each 4 week cycle plus MK-1775 200 mg orally QD on Days 1, 2, 8, 9, 15, and 16 of each 4 week cycle. | Participants received cisplatin 75 mg/ m^2 as an IV infusion on Day 1 of each 3 week cycle plus MK-1775 50 mg orally BID for 2.5 days, starting concomitantly with the administration of cisplatin on Day 1 and then at 12 hour intervals on Days 1-3 of each 3 week cycle. | Participants received cisplatin 75 mg/ m^2 as an IV infusion on Day 1 of each 3 week cycle plus MK-1775 100 mg orally BID for 2.5 days, starting concomitantly with the administration of cisplatin on Day 1 and then at 12 hour intervals on Days 1-3 of each 3 week cycle. | Participants received cisplatin 75 mg/ m^2 as an IV infusion on Day 1 of each 3 week cycle plus MK-1775 125 mg orally BID for 2.5 days, starting concomitantly with the administration of cisplatin on Day 1 and then at 12 hour intervals on Days 1-3 of each 3 week cycle. | Participants received cisplatin 75 mg/ m^2 as an IV infusion on Day 1 of each 3 week cycle plus MK-1775 150 mg orally BID for 2.5 days, starting concomitantly with the administration of cisplatin on Day 1 and then at 12 hour intervals on Days 1-3 of each 3 week cycle. | Participants received cisplatin 75 mg/ m^2 as an IV infusion on Day 1 of each 3 week cycle plus MK-1775 200 mg orally BID for 2.5 days, starting concomitantly with the administration of cisplatin on Day 1 and then at 12 hour intervals on Days 1-3 of each 3 week cycle. | Participants received cisplatin 75 mg/ m^2 as an IV infusion on Day 1 of each 3 week cycle plus MK-1775 250 mg orally BID for 2.5 days, starting concomitantly with the administration of cisplatin on Day 1 and then at 12 hour intervals on Days 1-3 of each 3 week cycle. | Participants received carboplatin AUC 5 as an IV infusion on Day 1 of each 3 week cycle plus MK-1775 75 mg orally BID for 2.5 days, starting concomitantly with the administration of carboplatin on Day 1 and then at 12 hour intervals on Days 1-3 of each 3 week cycle. | Participants received carboplatin AUC 5 as an IV infusion on Day 1 of each 3 week cycle plus MK-1775 150 mg orally BID for 2.5 days, starting concomitantly with the administration of carboplatin on Day 1 and then at 12 hour intervals on Days 1-3 of each 3 week cycle. | Participants received carboplatin AUC 5 as an IV infusion on Day 1 of each 3 week cycle plus MK-1775 225 mg orally BID for 2.5 days, starting concomitantly with the administration of carboplatin on Day 1 and then at 12 hour intervals on Days 1-3 of each 3 week cycle. | Participants received carboplatin AUC 5 as an IV infusion on Day 1 of each 3 week cycle plus MK-1775 325 mg orally BID for 2.5 days, starting concomitantly with the administration of carboplatin on Day 1 and then at 12 hour intervals on Days 1-3 of each 3 week cycle. |
| Measure Participants | 1 | 3 | 1 | 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 |
| Mean (Standard Deviation) [mg] |
16.7
(NA)
|
35.4
(9.86)
|
154
(NA)
|
| Title | Best Overall Response as Per Response Evaluation Criteria in Solid Tumors (RECIST) Criteria |
|---|---|
| Description | Best overall response achieved by a participant. Starting at Day 1, participants in Part 2 were evaluated for tumor response every 6-8 weeks until discontinuation from study treatment according to RECIST criteria; which are based on radiographic imaging. Recorded responses were either confirmed by Central Review or unconfirmed (Investigator assessment only), and included complete response (CR; defined as disappearance of all target lesions), partial response (PR; at least a 30% decrease in the sum of the longest diameter [LD] of target lesions, taking as reference the baseline sum LD), stable disease (SD; neither sufficient shrinkage to qualify for PR nor sufficient growth to qualify for PD, taking as reference the smallest sum LD since the treatment started), or progressive disease (PD; ≥20% increase in sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started, or the appearance of one or more new lesions). |
| Time Frame | From Day 1 up through discontinuation of study treatment (up to ~11.2 months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| All treated participants in Part 2 with measurable disease at baseline per RECIST criteria. Participants who were originally treated in Part 1 and continued in Part 2 were included in their respective Part 2 arms. Participants who could not be evaluated after treatment are categorized as "not evaluable (NE). |
| Arm/Group Title | MK-1775 325 mg Single Dose | MK-1775 650 mg Single Dose | MK-1775 1300 mg Single Dose | MK-1775 100 mg Single Dose + Gemcitabine 1000 mg/m^2 | MK-1775 200 mg Single Dose + Gemcitabine 1000 mg/m^2 | MK-1775 100 mg Single Dose + Cisplatin 75 mg/ m^2 | MK-1775 200 mg Single Dose + Cisplatin 75 mg/ m^2 | MK-1775 100 mg Single Dose + Carboplatin AUC 5 | MK-1775 200 mg Single Dose + Carboplatin AUC 5 | MK-1775 325 mg Single Dose + Carboplatin AUC 5 | MK-1775 25 mg BID x2.5 Multi Dose + Gemcitabine 1000 mg/ m^2 | MK-1775 50/25 mg BID x2.5 Multi + Gemcitabine 1000 mg/ m^2 | MK-1775 50 mg BID x2.5 Multi + Gemcitabine 1000 mg/ m^2 | MK-1775 100 mg QD x2 Multi + Gemcitabine 1000 mg/ m^2 | MK-1775 125 mg QD x2 Multi + Gemcitabine 1000 mg/ m^2 | MK-1775 150 mg QD x2 Multi + Gemcitabine 1000 mg/ m^2 | MK-1775 175 mg QD x2 Multi Dose + Gemcitabine 1000 mg/ m^2 | MK-1775 200 mg QD x2 Multi Dose + Gemcitabine 1000 mg/ m^2 | MK-1775 50 mg BID x2.5 Multi Dose + Cisplatin 75 mg/ m^2 | MK-1775 100 mg BID x2.5 Multi Dose + Cisplatin 75 mg/ m^2 | MK-1775 125 mg BID x2.5 Multi Dose + Cisplatin 75 mg/ m^2 | MK-1775 150 mg BID x2.5 Multi Dose + Cisplatin 75 mg/ m^2 | MK-1775 200 mg BID x2.5 Multi Dose + Cisplatin 75 mg/ m^2 | MK-1775 250 mg BID x2.5 Multi Dose + Cisplatin 75 mg/ m^2 | MK-1775 75 mg BID x2.5 Multi Dose + Carboplatin AUC 5 | MK-1775 150 mg BID x 2.5 Multi Dose + Carboplatin AUC 5 | MK-1775 225 mg BID x2.5 Multi Dose + Carboplatin AUC 5 | MK-1775 325 mg BID x2.5 Multi Dose + Carboplatin AUC 5 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants received MK-1775 325 mg, orally, on Day 1. | Participants received MK-1775 650 mg, orally, on Day 1. | Participants received MK-1775 1300 mg, orally, on Day 1. | Participants received gemcitabine 1000 mg/m^2 as an intravenous (IV) infusion on Days 1, 8, and 15 in each 4-week cycle plus MK-1775 100 mg single dose, orally, on Day 2 of each cycle. | Participants received gemcitabine 1000 mg/m^2 as an IV infusion on Days 1, 8, and 15 in each 4-week cycle plus MK-1775 200 mg single dose, orally, on Day 2 of each cycle. | Participants received cisplatin 75 mg/ m^2 as an IV infusion on Day 1 of each 3 week cycle plus MK-1775 100 mg single dose orally, on Day 2 of each cycle. | Participants received cisplatin 75 mg/ m^2 as an IV infusion on Day 1 of each 3 week cycle plus MK-1775 200 mg single dose orally, on Day 2 of each cycle. | Participants received carboplatin at an area under the time curve concentration of 5 mg/min/ml (AUC5) as an IV infusion on Day 1 of each 3 week cycle plus MK-1775 100 mg single dose orally, on Day 2 of each cycle. | Participants received carboplatin AUC5 as an IV infusion on Day 1 of each 3 week cycle plus MK-1775 200 mg single dose orally, on Day 2 of each cycle. | Participants received carboplatin AUC5 as an IV infusion on Day 1 of each 3 week cycle plus MK-1775 325 mg single dose orally, on Day 2 of each cycle. | Participants received gemcitabine 1000 mg/m^2 as an IV infusion on Days 1, 8, and 15 of each 4-week cycle plus MK-1775 25 mg orally twice daily (BID) for 2.5 days, starting concomitantly with the IV infusion of gemcitabine on Day 1 and followed by 4 additional doses of MK-1775 25 mg at approximately 12 hour intervals on Days 1-3, 8-9, and 15-17 of each cycle. | Participants received gemcitabine 1000 mg/m^2 as an IV infusion on Days 1, 8, and 15 of each 4 week cycle plus MK-1775 50 mg orally BID for 2.5 days, starting concomitantly with the IV infusion of gemcitabine on Day 1 and followed by 4 doses of MK-1775 25 mg at approximately 12 hour intervals on Days 1-3, 8-9, and 15-17 of each 4 week cycle. | Participants received gemcitabine 1000 mg/m^2 as an IV infusion given once weekly for 3 consecutive weeks of a 4 week cycle plus MK-1775 50 mg orally BID for 2.5 days, starting concomitantly with the IV infusion of gemcitabine on Day 1 and followed by 4 additional doses of MK-1775 50 mg at approximately 12 hour intervals on Days 1-3, 8-9, and 15-17 of each 4 week cycle. | Participants received gemcitabine 1000 mg/m^2 as an IV infusion on Days 1, 8, and 15 of each 4 week cycle plus MK-1775 100 mg orally once daily (QD) on Days 1, 2, 8, 9, 15, and 16 of each 4 week cycle. | Participants received gemcitabine 1000 mg/m^2 as an IV infusion on Days 1, 8, and 15 of each 4 week cycle plus MK-1775 125 mg orally QD on Days 1, 2, 8, 9, 15, and 16 of each 4 week cycle. | Participants received gemcitabine 1000 mg/m^2 as an IV infusion on Days 1, 8, and 15 of each 4 week cycle plus MK-1775 150 mg orally QD on Days 1, 2, 8, 9, 15, and 16 of each 4 week cycle. | Participants received gemcitabine 1000 mg/m^2 as an IV infusion given on Days 1, 8, and 15 of each 4 week cycle plus MK-1775 175 mg orally QD on Days 1, 2, 8, 9, 15, and 16 of each 4 week cycle. | Participants received gemcitabine 1000 mg/m^2 as an IV infusion on Days 1, 8, and 15 of each 4 week cycle plus MK-1775 200 mg orally QD on Days 1, 2, 8, 9, 15, and 16 of each 4 week cycle. | Participants received cisplatin 75 mg/ m^2 as an IV infusion on Day 1 of each 3 week cycle plus MK-1775 50 mg orally BID for 2.5 days, starting concomitantly with the administration of cisplatin on Day 1 and then at 12 hour intervals on Days 1-3 of each 3 week cycle. | Participants received cisplatin 75 mg/ m^2 as an IV infusion on Day 1 of each 3 week cycle plus MK-1775 100 mg orally BID for 2.5 days, starting concomitantly with the administration of cisplatin on Day 1 and then at 12 hour intervals on Days 1-3 of each 3 week cycle. | Participants received cisplatin 75 mg/ m^2 as an IV infusion on Day 1 of each 3 week cycle plus MK-1775 125 mg orally BID for 2.5 days, starting concomitantly with the administration of cisplatin on Day 1 and then at 12 hour intervals on Days 1-3 of each 3 week cycle. | Participants received cisplatin 75 mg/ m^2 as an IV infusion on Day 1 of each 3 week cycle plus MK-1775 150 mg orally BID for 2.5 days, starting concomitantly with the administration of cisplatin on Day 1 and then at 12 hour intervals on Days 1-3 of each 3 week cycle. | Participants received cisplatin 75 mg/ m^2 as an IV infusion on Day 1 of each 3 week cycle plus MK-1775 200 mg orally BID for 2.5 days, starting concomitantly with the administration of cisplatin on Day 1 and then at 12 hour intervals on Days 1-3 of each 3 week cycle. | Participants received cisplatin 75 mg/ m^2 as an IV infusion on Day 1 of each 3 week cycle plus MK-1775 250 mg orally BID for 2.5 days, starting concomitantly with the administration of cisplatin on Day 1 and then at 12 hour intervals on Days 1-3 of each 3 week cycle. | Participants received carboplatin AUC 5 as an IV infusion on Day 1 of each 3 week cycle plus MK-1775 75 mg orally BID for 2.5 days, starting concomitantly with the administration of carboplatin on Day 1 and then at 12 hour intervals on Days 1-3 of each 3 week cycle. | Participants received carboplatin AUC 5 as an IV infusion on Day 1 of each 3 week cycle plus MK-1775 150 mg orally BID for 2.5 days, starting concomitantly with the administration of carboplatin on Day 1 and then at 12 hour intervals on Days 1-3 of each 3 week cycle. | Participants received carboplatin AUC 5 as an IV infusion on Day 1 of each 3 week cycle plus MK-1775 225 mg orally BID for 2.5 days, starting concomitantly with the administration of carboplatin on Day 1 and then at 12 hour intervals on Days 1-3 of each 3 week cycle. | Participants received carboplatin AUC 5 as an IV infusion on Day 1 of each 3 week cycle plus MK-1775 325 mg orally BID for 2.5 days, starting concomitantly with the administration of carboplatin on Day 1 and then at 12 hour intervals on Days 1-3 of each 3 week cycle. |
| Measure Participants | 0 | 0 | 0 | 6 | 6 | 3 | 9 | 3 | 3 | 9 | 5 | 9 | 5 | 4 | 4 | 10 | 13 | 5 | 3 | 5 | 5 | 10 | 11 | 4 | 4 | 4 | 24 | 12 |
| CR |
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%
|
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%
|
| Confirmed PR |
0
0%
|
0
0%
|
0
0%
|
1
25%
|
0
0%
|
0
0%
|
1
10%
|
0
0%
|
0
0%
|
1
10%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
6.3%
|
0
0%
|
0
0%
|
2
28.6%
|
0
0%
|
0
0%
|
1
7.1%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Unconfirmed PR |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
100%
|
0
0%
|
0
0%
|
0
0%
|
1
10%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
6.3%
|
1
16.7%
|
0
0%
|
0
0%
|
0
0%
|
2
20%
|
1
7.1%
|
1
25%
|
0
0%
|
0
0%
|
2
7.7%
|
0
0%
|
| SD |
0
0%
|
0
0%
|
0
0%
|
3
75%
|
5
55.6%
|
0
0%
|
7
70%
|
0
0%
|
0
0%
|
3
30%
|
4
66.7%
|
4
30.8%
|
4
66.7%
|
2
40%
|
2
50%
|
8
72.7%
|
8
50%
|
3
50%
|
2
40%
|
1
14.3%
|
1
16.7%
|
4
40%
|
6
42.9%
|
2
50%
|
2
50%
|
3
75%
|
14
53.8%
|
6
50%
|
| PD |
0
0%
|
0
0%
|
0
0%
|
1
25%
|
1
11.1%
|
2
200%
|
1
10%
|
3
300%
|
3
100%
|
3
30%
|
1
16.7%
|
5
38.5%
|
1
16.7%
|
2
40%
|
2
50%
|
2
18.2%
|
3
18.8%
|
1
16.7%
|
1
20%
|
2
28.6%
|
4
66.7%
|
4
40%
|
3
21.4%
|
1
25%
|
2
50%
|
1
25%
|
8
30.8%
|
6
50%
|
| NE |
0
0%
|
0
0%
|
0
0%
|
1
25%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
10%
|
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%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Adverse Events
| Time Frame | Up to 30 days after the last dose of study drug (up to ~11.7 months) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | All participants receiving at least one dose of study medication. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Arm/Group Title | MK-1775 325 mg Single Dose | MK-1775 650 mg Single Dose | MK-1775 1300 mg Single Dose | MK-1775 100 mg Single Dose + Gemcitabine 1000 mg/m2 | MK-1775 200 mg Single Dose + Gemcitabine 1000 mg/m2 | MK-1775 100 mg Single Dose + Cisplatin 75 mg/m2 | MK-1775 200 mg Single Dose + Cisplatin 75 mg/m2 | MK-1775 100 mg Single Dose + Carboplatin AUC 5 | MK-1775 200 mg Single Dose + Carboplatin AUC 5 | MK-1775 325 mg Single Dose + Carboplatin AUC 5 | MK-1775 25 mg BID x2.5 Multi Dose + Gemcitabine 1000 mg/m2 | MK-1775 50/25 mg BID x2.5 Multi Dose + Gemcitabine 1000 mg/m2 | MK-1775 50 mg BID x2.5 Multi Dose + Gemcitabine 1000 mg/m2 | MK-1775 100 mg QD x2 Multi Dose + Gemcitabine 1000 mg/m2 | MK-1775 125 mg QD x2 Multi Dose + Gemcitabine 1000 mg/m2 | MK-1775 150 mg QD x2 Multi Dose + Gemcitabine 1000 mg/m2 | MK-1775 175 mg QD x2 Multi Dose + Gemcitabine 1000 mg/m2 | MK-1775 200 mg QD x2 Multi Dose + Gemcitabine 1000 mg/m2 | MK-1775 50 mg BID x2.5 Multi Dose + Cisplatin 75 mg/m2 | MK-1775 100 mg BID x2.5 Multi Dose + Cisplatin 75 mg/m2 | MK-1775 125 mg BID x2.5 Multi Dose + Cisplatin 75 mg/m2 | MK-1775 150 mg BID x2.5 Multi Dose + Cisplatin 75 mg/m2 | MK-1775 200 mg BID x2.5 Multi Dose + Cisplatin 75 mg/m2 | MK-1775 250 mg BID x2.5 Multi Dose + Cisplatin 75 mg/m2 | MK-1775 75 mg BID x2.5 Multi Dose + Carboplatin AUC 5 | MK-1775 150 mg BID x2.5 Multi Dose + Carboplatin AUC 5 | MK-1775 225 mg BID x2.5 Multi Dose + Carboplatin AUC 5 | MK-1775 325 mg BID x2.5 Multi Dose + Carboplatin AUC 5 | ||||||||||||||||||||||||||||
| Arm/Group Description | Participants received MK-1775 325 mg, orally, on Day 1. | Participants received MK-1775 650 mg, orally | Participants received MK-1775 1300 mg, orally, on Day 1. | Participants received gemcitabine 1000 mg/m^2 as an intravenous (IV) infusion on Days 1, 8, and 15 in each 4-week cycle plus MK-1775 100 mg single dose, orally, on Day 2 of each cycle. | Participants received gemcitabine 1000 mg/m^2 as an IV infusion on Days 1, 8, and 15 in each 4-week cycle plus MK-1775 200 mg single dose, orally, on Day 2 of each cycle. | Participants received cisplatin 75 mg/ m^2 as an IV infusion on Day 1 of each 3 week cycle plus MK-1775 100 mg single dose orally, on Day 2 of each cycle. | Participants received cisplatin 75 mg/ m^2 as an IV infusion on Day 1 of each 3 week cycle plus MK-1775 200 mg single dose orally, on Day 2 of each cycle. | Participants received carboplatin at an area under the time curve concentration of 5 mg/min/ml (AUC5) as an IV infusion on Day 1 of each 3 week cycle plus MK-1775 100 mg single dose orally, on Day 2 of each cycle. | Participants received carboplatin AUC5 as an IV infusion on Day 1 of each 3 week cycle plus MK-1775 200 mg single dose orally, on Day 2 of each cycle. | Participants received carboplatin AUC5 as an IV infusion on Day 1 of each 3 week cycle plus MK-1775 325 mg single dose orally, on Day 2 of each cycle. | Participants received gemcitabine 1000 mg/m^2 as an IV infusion on Days 1, 8, and 15 of each 4-week cycle plus MK-1775 25 mg orally twice daily (BID) for 2.5 days, starting concomitantly with the IV infusion of gemcitabine on Day 1 and followed by 4 additional doses of MK-1775 25 mg at approximately 12 hour intervals on Days 1-3, 8-9, and 15-17 of each cycle. | Participants received gemcitabine 1000 mg/m^2 as an IV infusion on Days 1, 8, and 15 of each 4 week cycle plus MK-1775 50 mg orally BID for 2.5 days, starting concomitantly with the IV infusion of gemcitabine on Day 1 and followed by 4 doses of MK-1775 25 mg at approximately 12 hour intervals on Days 1-3, 8-9, and 15-17 of each 4 week cycle. | Participants received gemcitabine 1000 mg/m^2 as an IV infusion given once weekly for 3 consecutive weeks of a 4 week cycle plus MK-1775 50 mg orally BID for 2.5 days, starting concomitantly with the IV infusion of gemcitabine on Day 1 and followed by 4 additional doses of MK-1775 50 mg at approximately 12 hour intervals on Days 1-3, 8-9, and 15-17 of each 4 week cycle. | Participants received gemcitabine 1000 mg/m^2 as an IV infusion on Days 1, 8, and 15 of each 4 week cycle plus MK-1775 100 mg orally once daily (QD) on Days 1, 2, 8, 9, 15, and 16 of each 4 week cycle. | Participants received gemcitabine 1000 mg/m^2 as an IV infusion on Days 1, 8, and 15 of each 4 week cycle plus MK-1775 125 mg orally QD on Days 1, 2, 8, 9, 15, and 16 of each 4 week cycle. | Participants received gemcitabine 1000 mg/m^2 as an IV infusion on Days 1, 8, and 15 of each 4 week cycle plus MK-1775 150 mg orally QD on Days 1, 2, 8, 9, 15, and 16 of each 4 week cycle. | Participants received gemcitabine 1000 mg/m^2 as an IV infusion given on Days 1, 8, and 15 of each 4 week cycle plus MK-1775 175 mg orally QD on Days 1, 2, 8, 9, 15, and 16 of each 4 week cycle. | Participants received gemcitabine 1000 mg/m^2 as an IV infusion on Days 1, 8, and 15 of each 4 week cycle plus MK-1775 200 mg orally QD on Days 1, 2, 8, 9, 15, and 16 of each 4 week cycle. | Participants received cisplatin 75 mg/ m^2 as an IV infusion on Day 1 of each 3 week cycle plus MK-1775 50 mg orally BID for 2.5 days, starting concomitantly with the administration of cisplatin on Day 1 and then at 12 hour intervals on Days 1-3 of each 3 week cycle. | Participants received cisplatin 75 mg/ m^2 as an IV infusion on Day 1 of each 3 week cycle plus MK-1775 100 mg orally BID for 2.5 days, starting concomitantly with the administration of cisplatin on Day 1 and then at 12 hour intervals on Days 1-3 of each 3 week cycle. | Participants received cisplatin 75 mg/ m^2 as an IV infusion on Day 1 of each 3 week cycle plus MK-1775 125 mg orally BID for 2.5 days, starting concomitantly with the administration of cisplatin on Day 1 and then at 12 hour intervals on Days 1-3 of each 3 week cycle. | Participants received cisplatin 75 mg/ m^2 as an IV infusion on Day 1 of each 3 week cycle plus MK-1775 150 mg orally BID for 2.5 days, starting concomitantly with the administration of cisplatin on Day 1 and then at 12 hour intervals on Days 1-3 of each 3 week cycle. | Participants received cisplatin 75 mg/ m^2 as an IV infusion on Day 1 of each 3 week cycle plus MK-1775 200 mg orally BID for 2.5 days, starting concomitantly with the administration of cisplatin on Day 1 and then at 12 hour intervals on Days 1-3 of each 3 week cycle. | Participants received cisplatin 75 mg/ m^2 as an IV infusion on Day 1 of each 3 week cycle plus MK-1775 250 mg orally BID for 2.5 days, starting concomitantly with the administration of cisplatin on Day 1 and then at 12 hour intervals on Days 1-3 of each 3 week cycle. | Participants received carboplatin AUC 5 as an IV infusion on Day 1 of each 3 week cycle plus MK-1775 75 mg orally BID for 2.5 days, starting concomitantly with the administration of carboplatin on Day 1 and then at 12 hour intervals on Days 1-3 of each 3 week cycle. | Participants received carboplatin AUC 5 as an IV infusion on Day 1 of each 3 week cycle plus MK-1775 150 mg orally BID for 2.5 days, starting concomitantly with the administration of carboplatin on Day 1 and then at 12 hour intervals on Days 1-3 of each 3 week cycle. | Participants received carboplatin AUC 5 as an IV infusion on Day 1 of each 3 week cycle plus MK-1775 225 mg orally BID for 2.5 days, starting concomitantly with the administration of carboplatin on Day 1 and then at 12 hour intervals on Days 1-3 of each 3 week cycle. | Participants received carboplatin AUC 5 as an IV infusion on Day 1 of each 3 week cycle plus MK-1775 325 mg orally BID for 2.5 days, starting concomitantly with the administration of carboplatin on Day 1 and then at 12 hour intervals on Days 1-3 of each 3 week cycle. | ||||||||||||||||||||||||||||
All Cause Mortality |
||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| MK-1775 325 mg Single Dose | MK-1775 650 mg Single Dose | MK-1775 1300 mg Single Dose | MK-1775 100 mg Single Dose + Gemcitabine 1000 mg/m2 | MK-1775 200 mg Single Dose + Gemcitabine 1000 mg/m2 | MK-1775 100 mg Single Dose + Cisplatin 75 mg/m2 | MK-1775 200 mg Single Dose + Cisplatin 75 mg/m2 | MK-1775 100 mg Single Dose + Carboplatin AUC 5 | MK-1775 200 mg Single Dose + Carboplatin AUC 5 | MK-1775 325 mg Single Dose + Carboplatin AUC 5 | MK-1775 25 mg BID x2.5 Multi Dose + Gemcitabine 1000 mg/m2 | MK-1775 50/25 mg BID x2.5 Multi Dose + Gemcitabine 1000 mg/m2 | MK-1775 50 mg BID x2.5 Multi Dose + Gemcitabine 1000 mg/m2 | MK-1775 100 mg QD x2 Multi Dose + Gemcitabine 1000 mg/m2 | MK-1775 125 mg QD x2 Multi Dose + Gemcitabine 1000 mg/m2 | MK-1775 150 mg QD x2 Multi Dose + Gemcitabine 1000 mg/m2 | MK-1775 175 mg QD x2 Multi Dose + Gemcitabine 1000 mg/m2 | MK-1775 200 mg QD x2 Multi Dose + Gemcitabine 1000 mg/m2 | MK-1775 50 mg BID x2.5 Multi Dose + Cisplatin 75 mg/m2 | MK-1775 100 mg BID x2.5 Multi Dose + Cisplatin 75 mg/m2 | MK-1775 125 mg BID x2.5 Multi Dose + Cisplatin 75 mg/m2 | MK-1775 150 mg BID x2.5 Multi Dose + Cisplatin 75 mg/m2 | MK-1775 200 mg BID x2.5 Multi Dose + Cisplatin 75 mg/m2 | MK-1775 250 mg BID x2.5 Multi Dose + Cisplatin 75 mg/m2 | MK-1775 75 mg BID x2.5 Multi Dose + Carboplatin AUC 5 | MK-1775 150 mg BID x2.5 Multi Dose + Carboplatin AUC 5 | MK-1775 225 mg BID x2.5 Multi Dose + Carboplatin AUC 5 | MK-1775 325 mg BID x2.5 Multi Dose + Carboplatin AUC 5 | |||||||||||||||||||||||||||||
| 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 | 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 | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 1/8 (12.5%) | 0/3 (0%) | 0/10 (0%) | 0/3 (0%) | 0/4 (0%) | 0/9 (0%) | 1/6 (16.7%) | 2/13 (15.4%) | 0/6 (0%) | 0/5 (0%) | 1/4 (25%) | 0/11 (0%) | 0/16 (0%) | 1/6 (16.7%) | 0/4 (0%) | 0/7 (0%) | 0/6 (0%) | 0/10 (0%) | 2/14 (14.3%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/26 (0%) | 1/12 (8.3%) | ||||||||||||||||||||||||||||
Serious Adverse Events |
||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| MK-1775 325 mg Single Dose | MK-1775 650 mg Single Dose | MK-1775 1300 mg Single Dose | MK-1775 100 mg Single Dose + Gemcitabine 1000 mg/m2 | MK-1775 200 mg Single Dose + Gemcitabine 1000 mg/m2 | MK-1775 100 mg Single Dose + Cisplatin 75 mg/m2 | MK-1775 200 mg Single Dose + Cisplatin 75 mg/m2 | MK-1775 100 mg Single Dose + Carboplatin AUC 5 | MK-1775 200 mg Single Dose + Carboplatin AUC 5 | MK-1775 325 mg Single Dose + Carboplatin AUC 5 | MK-1775 25 mg BID x2.5 Multi Dose + Gemcitabine 1000 mg/m2 | MK-1775 50/25 mg BID x2.5 Multi Dose + Gemcitabine 1000 mg/m2 | MK-1775 50 mg BID x2.5 Multi Dose + Gemcitabine 1000 mg/m2 | MK-1775 100 mg QD x2 Multi Dose + Gemcitabine 1000 mg/m2 | MK-1775 125 mg QD x2 Multi Dose + Gemcitabine 1000 mg/m2 | MK-1775 150 mg QD x2 Multi Dose + Gemcitabine 1000 mg/m2 | MK-1775 175 mg QD x2 Multi Dose + Gemcitabine 1000 mg/m2 | MK-1775 200 mg QD x2 Multi Dose + Gemcitabine 1000 mg/m2 | MK-1775 50 mg BID x2.5 Multi Dose + Cisplatin 75 mg/m2 | MK-1775 100 mg BID x2.5 Multi Dose + Cisplatin 75 mg/m2 | MK-1775 125 mg BID x2.5 Multi Dose + Cisplatin 75 mg/m2 | MK-1775 150 mg BID x2.5 Multi Dose + Cisplatin 75 mg/m2 | MK-1775 200 mg BID x2.5 Multi Dose + Cisplatin 75 mg/m2 | MK-1775 250 mg BID x2.5 Multi Dose + Cisplatin 75 mg/m2 | MK-1775 75 mg BID x2.5 Multi Dose + Carboplatin AUC 5 | MK-1775 150 mg BID x2.5 Multi Dose + Carboplatin AUC 5 | MK-1775 225 mg BID x2.5 Multi Dose + Carboplatin AUC 5 | MK-1775 325 mg BID x2.5 Multi Dose + Carboplatin AUC 5 | |||||||||||||||||||||||||||||
| 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 | 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 | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/6 (16.7%) | 3/8 (37.5%) | 1/3 (33.3%) | 3/10 (30%) | 1/3 (33.3%) | 1/4 (25%) | 1/9 (11.1%) | 3/6 (50%) | 6/13 (46.2%) | 0/6 (0%) | 2/5 (40%) | 3/4 (75%) | 4/11 (36.4%) | 4/16 (25%) | 5/6 (83.3%) | 1/4 (25%) | 0/7 (0%) | 3/6 (50%) | 5/10 (50%) | 6/14 (42.9%) | 2/4 (50%) | 1/4 (25%) | 0/4 (0%) | 13/26 (50%) | 7/12 (58.3%) | ||||||||||||||||||||||||||||
| Blood and lymphatic system disorders | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Anaemia | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 1/6 (16.7%) | 2 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 1/14 (7.1%) | 1 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 2/26 (7.7%) | 2 | 0/12 (0%) | 0 |
| Febrile neutropenia | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 2/6 (33.3%) | 2 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 2/26 (7.7%) | 2 | 1/12 (8.3%) | 1 |
| Leukopenia | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 1/11 (9.1%) | 1 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 |
| Neutropenia | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 1/12 (8.3%) | 1 |
| Thrombocytopenia | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 1/14 (7.1%) | 1 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/26 (3.8%) | 1 | 0/12 (0%) | 0 |
| Cardiac disorders | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Myocardial infarction | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 2/16 (12.5%) | 2 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 |
| Palpitations | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 1/5 (20%) | 1 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 |
| Supraventricular tachycardia | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 1/10 (10%) | 1 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 |
| Gastrointestinal disorders | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Abdominal pain | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 1/3 (33.3%) | 1 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 1/4 (25%) | 1 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 1/14 (7.1%) | 1 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 |
| Abdominal pain upper | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/26 (3.8%) | 1 | 0/12 (0%) | 0 |
| Colitis | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 1/4 (25%) | 1 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 |
| Constipation | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/26 (3.8%) | 1 | 0/12 (0%) | 0 |
| Diarrhoea | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 1/10 (10%) | 1 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 3/26 (11.5%) | 3 | 1/12 (8.3%) | 1 |
| Faecaloma | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 1/4 (25%) | 2 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 |
| Gastric perforation | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 1/16 (6.3%) | 1 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 |
| Gastric ulcer | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 1/10 (10%) | 1 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 |
| Haematemesis | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 1/6 (16.7%) | 1 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 |
| Haemorrhoidal haemorrhage | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/26 (3.8%) | 3 | 0/12 (0%) | 0 |
| Nausea | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 1/3 (33.3%) | 3 | 1/10 (10%) | 1 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 1/10 (10%) | 1 | 2/14 (14.3%) | 2 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 2/26 (7.7%) | 2 | 0/12 (0%) | 0 |
| Small intestinal obstruction | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 1/14 (7.1%) | 1 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 |
| Vomiting | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 1/3 (33.3%) | 1 | 1/10 (10%) | 1 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 2/14 (14.3%) | 2 | 0/4 (0%) | 0 | 1/4 (25%) | 1 | 0/4 (0%) | 0 | 1/26 (3.8%) | 1 | 1/12 (8.3%) | 1 |
| General disorders | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Asthenia | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 1/11 (9.1%) | 1 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 |
| Chest pain | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 1/12 (8.3%) | 1 |
| Drug withdrawal syndrome | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 1/12 (8.3%) | 1 |
| Non-cardiac chest pain | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 1/16 (6.3%) | 1 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 |
| Pain | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 1/12 (8.3%) | 1 |
| Pyrexia | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 1/8 (12.5%) | 1 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 1/6 (16.7%) | 2 | 1/13 (7.7%) | 1 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 1/11 (9.1%) | 1 | 0/16 (0%) | 0 | 1/6 (16.7%) | 1 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 1/6 (16.7%) | 1 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/26 (3.8%) | 1 | 0/12 (0%) | 0 |
| Hepatobiliary disorders | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Hepatitis | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 1/9 (11.1%) | 1 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 |
| Hyperbilirubinaemia | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 1/13 (7.7%) | 1 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 |
| Infections and infestations | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Abdominal abscess | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 1/6 (16.7%) | 1 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 |
| Cellulitis | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 1/11 (9.1%) | 1 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 |
| Gastroenteritis | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 1/13 (7.7%) | 1 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 |
| Influenza | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 1/14 (7.1%) | 1 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 |
| Osteomyelitis | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 1/11 (9.1%) | 1 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 |
| Pneumonia | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 2/13 (15.4%) | 2 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 1/6 (16.7%) | 1 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 |
| Urinary tract infection | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 1/16 (6.3%) | 1 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 1/4 (25%) | 1 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 |
| Injury, poisoning and procedural complications | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Pelvic fracture | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 1/11 (9.1%) | 1 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 |
| Recall phenomenon | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 1/11 (9.1%) | 1 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 |
| Investigations | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Blood creatinine increased | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 1/10 (10%) | 1 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/26 (3.8%) | 1 | 0/12 (0%) | 0 |
| Electrocardiogram ST-T segment elevation | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 1/16 (6.3%) | 1 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 |
| Metabolism and nutrition disorders | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Dehydration | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 1/14 (7.1%) | 1 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 1/12 (8.3%) | 1 |
| Electrolyte imbalance | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 1/6 (16.7%) | 1 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 |
| Hypercalcaemia | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 1/6 (16.7%) | 1 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 |
| Hypoglycaemia | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 1/14 (7.1%) | 1 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 |
| Hyponatraemia | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 1/12 (8.3%) | 1 |
| Hypophosphataemia | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/26 (3.8%) | 1 | 0/12 (0%) | 0 |
| Musculoskeletal and connective tissue disorders | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Pain in extremity | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/26 (3.8%) | 1 | 0/12 (0%) | 0 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Colon cancer | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 1/3 (33.3%) | 1 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 |
| Malignant melanoma | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/26 (3.8%) | 1 | 0/12 (0%) | 0 |
| Malignant neoplasm progression | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 1/6 (16.7%) | 1 | 1/13 (7.7%) | 1 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 1/10 (10%) | 1 | 2/14 (14.3%) | 2 | 0/4 (0%) | 0 | 1/4 (25%) | 1 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 1/12 (8.3%) | 1 |
| Metastases to spine | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 1/8 (12.5%) | 1 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 |
| Nervous system disorders | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Hemiparesis | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 1/10 (10%) | 1 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 |
| Spinal cord compression | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 1/5 (20%) | 1 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 |
| Transient ischaemic attack | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 1/10 (10%) | 1 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 |
| Psychiatric disorders | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Agitation | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/26 (3.8%) | 1 | 0/12 (0%) | 0 |
| Renal and urinary disorders | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Renal failure | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 1/11 (9.1%) | 1 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 1/14 (7.1%) | 1 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 |
| Renal failure acute | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 1/13 (7.7%) | 1 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 |
| Renal impairment | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 1/6 (16.7%) | 1 | 1/10 (10%) | 1 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 |
| Urinary retention | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 1/5 (20%) | 1 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 |
| Reproductive system and breast disorders | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Female genital tract fistula | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/26 (3.8%) | 1 | 0/12 (0%) | 0 |
| Respiratory, thoracic and mediastinal disorders | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Dyspnoea | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 1/3 (33.3%) | 1 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 1/5 (20%) | 1 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 1/16 (6.3%) | 1 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 1/12 (8.3%) | 1 |
| Hypoxia | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 1/8 (12.5%) | 1 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 |
| Lung infiltration | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 1/4 (25%) | 1 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 |
| Pleural effusion | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 1/4 (25%) | 1 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 1/4 (25%) | 1 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 |
| Pulmonary embolism | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 1/13 (7.7%) | 1 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 |
| Respiratory failure | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 1/13 (7.7%) | 1 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 |
| Vascular disorders | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Haemorrhage | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 1/4 (25%) | 1 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 |
| Thrombophlebitis | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 1/3 (33.3%) | 1 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 |
Other (Not Including Serious) Adverse Events |
||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| MK-1775 325 mg Single Dose | MK-1775 650 mg Single Dose | MK-1775 1300 mg Single Dose | MK-1775 100 mg Single Dose + Gemcitabine 1000 mg/m2 | MK-1775 200 mg Single Dose + Gemcitabine 1000 mg/m2 | MK-1775 100 mg Single Dose + Cisplatin 75 mg/m2 | MK-1775 200 mg Single Dose + Cisplatin 75 mg/m2 | MK-1775 100 mg Single Dose + Carboplatin AUC 5 | MK-1775 200 mg Single Dose + Carboplatin AUC 5 | MK-1775 325 mg Single Dose + Carboplatin AUC 5 | MK-1775 25 mg BID x2.5 Multi Dose + Gemcitabine 1000 mg/m2 | MK-1775 50/25 mg BID x2.5 Multi Dose + Gemcitabine 1000 mg/m2 | MK-1775 50 mg BID x2.5 Multi Dose + Gemcitabine 1000 mg/m2 | MK-1775 100 mg QD x2 Multi Dose + Gemcitabine 1000 mg/m2 | MK-1775 125 mg QD x2 Multi Dose + Gemcitabine 1000 mg/m2 | MK-1775 150 mg QD x2 Multi Dose + Gemcitabine 1000 mg/m2 | MK-1775 175 mg QD x2 Multi Dose + Gemcitabine 1000 mg/m2 | MK-1775 200 mg QD x2 Multi Dose + Gemcitabine 1000 mg/m2 | MK-1775 50 mg BID x2.5 Multi Dose + Cisplatin 75 mg/m2 | MK-1775 100 mg BID x2.5 Multi Dose + Cisplatin 75 mg/m2 | MK-1775 125 mg BID x2.5 Multi Dose + Cisplatin 75 mg/m2 | MK-1775 150 mg BID x2.5 Multi Dose + Cisplatin 75 mg/m2 | MK-1775 200 mg BID x2.5 Multi Dose + Cisplatin 75 mg/m2 | MK-1775 250 mg BID x2.5 Multi Dose + Cisplatin 75 mg/m2 | MK-1775 75 mg BID x2.5 Multi Dose + Carboplatin AUC 5 | MK-1775 150 mg BID x2.5 Multi Dose + Carboplatin AUC 5 | MK-1775 225 mg BID x2.5 Multi Dose + Carboplatin AUC 5 | MK-1775 325 mg BID x2.5 Multi Dose + Carboplatin AUC 5 | |||||||||||||||||||||||||||||
| 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 | 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 | 2/3 (66.7%) | 3/3 (100%) | 1/3 (33.3%) | 6/6 (100%) | 8/8 (100%) | 3/3 (100%) | 10/10 (100%) | 3/3 (100%) | 2/4 (50%) | 9/9 (100%) | 6/6 (100%) | 13/13 (100%) | 6/6 (100%) | 5/5 (100%) | 4/4 (100%) | 11/11 (100%) | 16/16 (100%) | 6/6 (100%) | 4/4 (100%) | 7/7 (100%) | 6/6 (100%) | 10/10 (100%) | 13/14 (92.9%) | 4/4 (100%) | 4/4 (100%) | 4/4 (100%) | 26/26 (100%) | 12/12 (100%) | ||||||||||||||||||||||||||||
| Blood and lymphatic system disorders | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Anaemia | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 2/6 (33.3%) | 7 | 4/8 (50%) | 4 | 0/3 (0%) | 0 | 3/10 (30%) | 5 | 1/3 (33.3%) | 1 | 0/4 (0%) | 0 | 4/9 (44.4%) | 6 | 4/6 (66.7%) | 11 | 9/13 (69.2%) | 15 | 2/6 (33.3%) | 4 | 1/5 (20%) | 9 | 1/4 (25%) | 1 | 8/11 (72.7%) | 18 | 3/16 (18.8%) | 4 | 2/6 (33.3%) | 5 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 2/6 (33.3%) | 3 | 4/10 (40%) | 5 | 3/14 (21.4%) | 4 | 2/4 (50%) | 4 | 1/4 (25%) | 1 | 0/4 (0%) | 0 | 13/26 (50%) | 25 | 5/12 (41.7%) | 18 | |||
| Leukocytosis | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 1/13 (7.7%) | 1 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/26 (3.8%) | 1 | 0/12 (0%) | 0 | |||
| Leukopenia | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 4/8 (50%) | 5 | 0/3 (0%) | 0 | 1/10 (10%) | 2 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 2/9 (22.2%) | 5 | 2/6 (33.3%) | 4 | 3/13 (23.1%) | 4 | 1/6 (16.7%) | 3 | 1/5 (20%) | 1 | 1/4 (25%) | 1 | 3/11 (27.3%) | 6 | 2/16 (12.5%) | 3 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 1/6 (16.7%) | 1 | 1/10 (10%) | 1 | 0/14 (0%) | 0 | 3/4 (75%) | 5 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 3/26 (11.5%) | 9 | 3/12 (25%) | 8 | |||
| Neutropenia | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/6 (16.7%) | 3 | 3/8 (37.5%) | 4 | 1/3 (33.3%) | 1 | 3/10 (30%) | 6 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 2/9 (22.2%) | 7 | 2/6 (33.3%) | 2 | 1/13 (7.7%) | 1 | 4/6 (66.7%) | 18 | 0/5 (0%) | 0 | 1/4 (25%) | 1 | 7/11 (63.6%) | 21 | 10/16 (62.5%) | 20 | 4/6 (66.7%) | 6 | 0/4 (0%) | 0 | 3/7 (42.9%) | 4 | 0/6 (0%) | 0 | 4/10 (40%) | 4 | 4/14 (28.6%) | 10 | 1/4 (25%) | 1 | 1/4 (25%) | 1 | 0/4 (0%) | 0 | 10/26 (38.5%) | 14 | 5/12 (41.7%) | 14 | |||
| Pancytopenia | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/26 (3.8%) | 1 | 2/12 (16.7%) | 2 | |||
| Thrombocytopenia | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/6 (16.7%) | 1 | 3/8 (37.5%) | 5 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 1/3 (33.3%) | 1 | 0/4 (0%) | 0 | 5/9 (55.6%) | 12 | 3/6 (50%) | 8 | 8/13 (61.5%) | 16 | 4/6 (66.7%) | 14 | 2/5 (40%) | 7 | 3/4 (75%) | 13 | 8/11 (72.7%) | 34 | 9/16 (56.3%) | 21 | 4/6 (66.7%) | 7 | 0/4 (0%) | 0 | 1/7 (14.3%) | 1 | 2/6 (33.3%) | 2 | 3/10 (30%) | 3 | 5/14 (35.7%) | 18 | 4/4 (100%) | 12 | 1/4 (25%) | 1 | 1/4 (25%) | 2 | 19/26 (73.1%) | 53 | 6/12 (50%) | 25 | |||
| Thrombocytosis | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 1/13 (7.7%) | 1 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 1/10 (10%) | 1 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/26 (3.8%) | 2 | 0/12 (0%) | 0 | |||
| Cardiac disorders | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Angina pectoris | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 1/16 (6.3%) | 1 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 | |||
| Cardiomegaly | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 1/4 (25%) | 1 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 | |||
| Palpitations | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 1/4 (25%) | 1 | 2/11 (18.2%) | 2 | 1/16 (6.3%) | 1 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 1/12 (8.3%) | 1 | |||
| Sinus bradycardia | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 1/6 (16.7%) | 1 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 1/4 (25%) | 1 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 | |||
| Sinus tachycardia | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 1/10 (10%) | 1 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 1/12 (8.3%) | 1 | |||
| Supraventricular extrasystoles | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 1/5 (20%) | 1 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 | |||
| Tachycardia | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 1/13 (7.7%) | 1 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 1/6 (16.7%) | 1 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/26 (3.8%) | 1 | 0/12 (0%) | 0 | |||
| Ear and labyrinth disorders | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cerumen impaction | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 1/16 (6.3%) | 1 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 | |||
| Deafness | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 1/16 (6.3%) | 1 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 | |||
| Deafness bilateral | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 1/6 (16.7%) | 1 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 1/7 (14.3%) | 1 | 0/6 (0%) | 0 | 1/10 (10%) | 1 | 1/14 (7.1%) | 1 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 | |||
| Deafness unilateral | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/4 (25%) | 1 | 1/26 (3.8%) | 1 | 0/12 (0%) | 0 | |||
| Ear congestion | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 1/12 (8.3%) | 1 | |||
| Ear pain | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 1/10 (10%) | 1 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 | |||
| External ear pain | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 1/13 (7.7%) | 1 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 | |||
| Hypoacusis | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 1/10 (10%) | 1 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 1/7 (14.3%) | 1 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 1/14 (7.1%) | 1 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 | |||
| Tinnitus | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 2/3 (66.7%) | 2 | 1/10 (10%) | 1 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 2/7 (28.6%) | 2 | 3/6 (50%) | 3 | 3/10 (30%) | 5 | 2/14 (14.3%) | 2 | 1/4 (25%) | 1 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/26 (3.8%) | 1 | 0/12 (0%) | 0 | |||
| Eye disorders | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cataract | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 1/4 (25%) | 1 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 | |||
| Conjunctivitis | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 1/12 (8.3%) | 1 | |||
| Deposit eye | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 1/9 (11.1%) | 1 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 | |||
| Diplopia | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 1/10 (10%) | 1 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 | |||
| Eye discharge | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 1/6 (16.7%) | 1 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 | |||
| Eye pain | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 1/13 (7.7%) | 1 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/26 (3.8%) | 1 | 0/12 (0%) | 0 | |||
| Eye swelling | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 3/11 (27.3%) | 4 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 | |||
| Lacrimation increased | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 1/11 (9.1%) | 2 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 1/10 (10%) | 1 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/4 (25%) | 1 | 0/26 (0%) | 0 | 0/12 (0%) | 0 | |||
| Ophthalmoplegia | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 1/13 (7.7%) | 3 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 | |||
| Photophobia | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 1/13 (7.7%) | 1 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 | |||
| Photopsia | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 1/13 (7.7%) | 1 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 | |||
| Scleral haemorrhage | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 1/13 (7.7%) | 1 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 | |||
| Vision blurred | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 2/6 (33.3%) | 2 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 1/7 (14.3%) | 2 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/26 (3.8%) | 1 | 1/12 (8.3%) | 1 | |||
| Visual impairment | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 2/10 (20%) | 2 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 | |||
| Gastrointestinal disorders | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Abdominal discomfort | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 1/13 (7.7%) | 1 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 1/7 (14.3%) | 1 | 0/6 (0%) | 0 | 2/10 (20%) | 2 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/26 (3.8%) | 2 | 0/12 (0%) | 0 | |||
| Abdominal distension | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/6 (16.7%) | 1 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 1/10 (10%) | 1 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 1/13 (7.7%) | 1 | 1/6 (16.7%) | 1 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 1/6 (16.7%) | 1 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 1/10 (10%) | 1 | 2/14 (14.3%) | 3 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/4 (25%) | 1 | 0/26 (0%) | 0 | 3/12 (25%) | 5 | |||
| Abdominal hernia | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 1/8 (12.5%) | 1 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 1/13 (7.7%) | 1 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 | |||
| Abdominal pain | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 2/6 (33.3%) | 3 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 1/3 (33.3%) | 1 | 0/4 (0%) | 0 | 3/9 (33.3%) | 3 | 0/6 (0%) | 0 | 3/13 (23.1%) | 4 | 1/6 (16.7%) | 2 | 0/5 (0%) | 0 | 2/4 (50%) | 5 | 0/11 (0%) | 0 | 5/16 (31.3%) | 7 | 2/6 (33.3%) | 5 | 2/4 (50%) | 2 | 0/7 (0%) | 0 | 1/6 (16.7%) | 1 | 3/10 (30%) | 3 | 3/14 (21.4%) | 6 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/4 (25%) | 2 | 0/26 (0%) | 0 | 4/12 (33.3%) | 6 | |||
| Abdominal pain lower | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 1/13 (7.7%) | 1 | 1/6 (16.7%) | 1 | 1/5 (20%) | 1 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 1/6 (16.7%) | 1 | 0/10 (0%) | 0 | 1/14 (7.1%) | 1 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/26 (3.8%) | 1 | 0/12 (0%) | 0 | |||
| Abdominal pain upper | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 1/8 (12.5%) | 1 | 0/3 (0%) | 0 | 1/10 (10%) | 1 | 0/3 (0%) | 0 | 1/4 (25%) | 1 | 1/9 (11.1%) | 1 | 1/6 (16.7%) | 1 | 1/13 (7.7%) | 1 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 1/16 (6.3%) | 1 | 2/6 (33.3%) | 2 | 0/4 (0%) | 0 | 1/7 (14.3%) | 1 | 0/6 (0%) | 0 | 3/10 (30%) | 3 | 1/14 (7.1%) | 3 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/26 (3.8%) | 1 | 1/12 (8.3%) | 1 | |||
| Anal fissure | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 1/11 (9.1%) | 1 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 | |||
| Anal inflammation | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 1/13 (7.7%) | 1 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 | |||
| Anorectal discomfort | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 1/6 (16.7%) | 2 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 1/4 (25%) | 1 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 | |||
| Ascites | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 1/13 (7.7%) | 1 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 1/11 (9.1%) | 1 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 1/14 (7.1%) | 2 | 1/4 (25%) | 1 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 | |||
| Chapped lips | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 1/11 (9.1%) | 1 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 | |||
| Cheilitis | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 2/6 (33.3%) | 3 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 1/7 (14.3%) | 1 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 | |||
| Colitis ischaemic | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 1/11 (9.1%) | 1 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 | |||
| Constipation | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 3/6 (50%) | 3 | 0/8 (0%) | 0 | 2/3 (66.7%) | 2 | 2/10 (20%) | 2 | 0/3 (0%) | 0 | 1/4 (25%) | 1 | 3/9 (33.3%) | 6 | 1/6 (16.7%) | 1 | 6/13 (46.2%) | 6 | 2/6 (33.3%) | 3 | 2/5 (40%) | 2 | 3/4 (75%) | 3 | 2/11 (18.2%) | 10 | 6/16 (37.5%) | 10 | 3/6 (50%) | 8 | 3/4 (75%) | 6 | 3/7 (42.9%) | 4 | 0/6 (0%) | 0 | 8/10 (80%) | 14 | 7/14 (50%) | 10 | 1/4 (25%) | 2 | 0/4 (0%) | 0 | 1/4 (25%) | 3 | 13/26 (50%) | 24 | 3/12 (25%) | 6 | |||
| Diarrhoea | 0/3 (0%) | 2/3 (66.7%) | 2 | 0/3 (0%) | 2 | 1/6 (16.7%) | 1 | 2/8 (25%) | 4 | 1/3 (33.3%) | 1 | 5/10 (50%) | 8 | 1/3 (33.3%) | 1 | 1/4 (25%) | 1 | 3/9 (33.3%) | 4 | 2/6 (33.3%) | 3 | 5/13 (38.5%) | 6 | 5/6 (83.3%) | 8 | 2/5 (40%) | 3 | 1/4 (25%) | 1 | 5/11 (45.5%) | 7 | 5/16 (31.3%) | 7 | 4/6 (66.7%) | 8 | 1/4 (25%) | 2 | 3/7 (42.9%) | 13 | 2/6 (33.3%) | 2 | 6/10 (60%) | 12 | 6/14 (42.9%) | 14 | 3/4 (75%) | 3 | 2/4 (50%) | 2 | 3/4 (75%) | 4 | 18/26 (69.2%) | 47 | 11/12 (91.7%) | 20 | |
| Dry mouth | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 1/14 (7.1%) | 1 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 2/12 (16.7%) | 2 | |||
| Duodenitis | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 1/14 (7.1%) | 1 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 | |||
| Dyspepsia | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 1/3 (33.3%) | 1 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 1/9 (11.1%) | 4 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 1/6 (16.7%) | 1 | 1/5 (20%) | 1 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 2/7 (28.6%) | 2 | 0/6 (0%) | 0 | 1/10 (10%) | 1 | 2/14 (14.3%) | 2 | 1/4 (25%) | 1 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 5/26 (19.2%) | 10 | 2/12 (16.7%) | 3 | |||
| Dysphagia | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 1/8 (12.5%) | 1 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 2/6 (33.3%) | 2 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 1/6 (16.7%) | 1 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 1/14 (7.1%) | 1 | 0/4 (0%) | 0 | 1/4 (25%) | 1 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 | |||
| Eructation | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 1/5 (20%) | 1 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 3/10 (30%) | 4 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 1/12 (8.3%) | 1 | |||
| Faecal incontinence | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 1/13 (7.7%) | 1 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 | |||
| Flatulence | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 1/10 (10%) | 1 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 1/13 (7.7%) | 1 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 1/11 (9.1%) | 1 | 1/16 (6.3%) | 1 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 1/14 (7.1%) | 1 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 1/12 (8.3%) | 1 | |||
| Gastritis | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 1/6 (16.7%) | 1 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 | |||
| Gastrointestinal haemorrhage | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 1/6 (16.7%) | 2 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 1/16 (6.3%) | 1 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 | |||
| Gastrointestinal ulcer | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 1/14 (7.1%) | 1 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 | |||
| Gastrooesophageal reflux disease | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 1/8 (12.5%) | 1 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 | |||
| Haematochezia | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 1/13 (7.7%) | 1 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 1/11 (9.1%) | 1 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 | |||
| Haemorrhoids | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 1/13 (7.7%) | 1 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 1/11 (9.1%) | 1 | 1/16 (6.3%) | 1 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 | |||
| Hyperchlorhydria | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 1/12 (8.3%) | 1 | |||
| Ileus | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 1/12 (8.3%) | 1 | |||
| Melaena | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 1/6 (16.7%) | 1 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 | |||
| Nausea | 1/3 (33.3%) | 1 | 0/3 (0%) | 1 | 0/3 (0%) | 1 | 4/6 (66.7%) | 7 | 5/8 (62.5%) | 13 | 1/3 (33.3%) | 3 | 8/10 (80%) | 14 | 1/3 (33.3%) | 1 | 1/4 (25%) | 1 | 5/9 (55.6%) | 11 | 4/6 (66.7%) | 14 | 7/13 (53.8%) | 14 | 4/6 (66.7%) | 5 | 4/5 (80%) | 8 | 4/4 (100%) | 6 | 9/11 (81.8%) | 15 | 9/16 (56.3%) | 15 | 4/6 (66.7%) | 11 | 4/4 (100%) | 9 | 6/7 (85.7%) | 13 | 6/6 (100%) | 10 | 10/10 (100%) | 25 | 12/14 (85.7%) | 46 | 4/4 (100%) | 8 | 3/4 (75%) | 4 | 3/4 (75%) | 11 | 17/26 (65.4%) | 38 | 8/12 (66.7%) | 20 |
| Oesophageal pain | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 1/6 (16.7%) | 1 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 | |||
| Oral pain | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 1/6 (16.7%) | 1 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 2/7 (28.6%) | 2 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 | |||
| Oral pruritus | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 1/12 (8.3%) | 1 | |||
| Paraesthesia oral | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 1/6 (16.7%) | 1 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/26 (3.8%) | 1 | 0/12 (0%) | 0 | |||
| Periodontal disease | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 1/16 (6.3%) | 1 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 | |||
| Post-tussive vomiting | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 1/6 (16.7%) | 1 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 | |||
| Proctalgia | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 1/11 (9.1%) | 1 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 1/12 (8.3%) | 1 | |||
| Rectal haemorrhage | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 1/11 (9.1%) | 1 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 | |||
| Retching | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 1/14 (7.1%) | 1 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 1/12 (8.3%) | 1 | |||
| Sensitivity of teeth | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 1/9 (11.1%) | 1 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 1/14 (7.1%) | 1 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 | |||
| Stomatitis | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 2/8 (25%) | 3 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 1/13 (7.7%) | 2 | 0/6 (0%) | 0 | 1/5 (20%) | 2 | 1/4 (25%) | 1 | 3/11 (27.3%) | 4 | 2/16 (12.5%) | 2 | 1/6 (16.7%) | 2 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 1/6 (16.7%) | 1 | 1/10 (10%) | 1 | 2/14 (14.3%) | 2 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/4 (25%) | 1 | 4/26 (15.4%) | 6 | 3/12 (25%) | 3 | |||
| Vomiting | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/6 (16.7%) | 2 | 4/8 (50%) | 10 | 1/3 (33.3%) | 1 | 5/10 (50%) | 9 | 0/3 (0%) | 0 | 1/4 (25%) | 1 | 2/9 (22.2%) | 4 | 1/6 (16.7%) | 10 | 3/13 (23.1%) | 4 | 1/6 (16.7%) | 1 | 2/5 (40%) | 3 | 2/4 (50%) | 3 | 3/11 (27.3%) | 4 | 4/16 (25%) | 4 | 4/6 (66.7%) | 8 | 2/4 (50%) | 2 | 5/7 (71.4%) | 9 | 1/6 (16.7%) | 1 | 6/10 (60%) | 15 | 8/14 (57.1%) | 13 | 3/4 (75%) | 3 | 3/4 (75%) | 3 | 3/4 (75%) | 5 | 11/26 (42.3%) | 15 | 7/12 (58.3%) | 14 | |||
| General disorders | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Asthenia | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 1/9 (11.1%) | 1 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 1/16 (6.3%) | 1 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 2/10 (20%) | 2 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/4 (25%) | 1 | 0/26 (0%) | 0 | 1/12 (8.3%) | 1 | |||
| Axillary pain | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 1/9 (11.1%) | 1 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 | |||
| Catheter site pain | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 1/13 (7.7%) | 1 | 1/6 (16.7%) | 1 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 1/12 (8.3%) | 1 | |||
| Chest pain | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 1/6 (16.7%) | 1 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 1/5 (20%) | 1 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 1/7 (14.3%) | 1 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/4 (25%) | 2 | 0/26 (0%) | 0 | 1/12 (8.3%) | 1 | |||
| Chills | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 1/8 (12.5%) | 2 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 1/6 (16.7%) | 1 | 2/13 (15.4%) | 3 | 1/6 (16.7%) | 1 | 0/5 (0%) | 0 | 1/4 (25%) | 2 | 1/11 (9.1%) | 3 | 0/16 (0%) | 0 | 2/6 (33.3%) | 4 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 4/14 (28.6%) | 4 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 2/26 (7.7%) | 2 | 1/12 (8.3%) | 3 | |||
| Face oedema | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 1/10 (10%) | 1 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 | |||
| Fatigue | 0/3 (0%) | 1/3 (33.3%) | 1 | 1/3 (33.3%) | 1 | 5/6 (83.3%) | 12 | 5/8 (62.5%) | 7 | 2/3 (66.7%) | 2 | 6/10 (60%) | 13 | 2/3 (66.7%) | 2 | 1/4 (25%) | 1 | 4/9 (44.4%) | 7 | 6/6 (100%) | 18 | 6/13 (46.2%) | 10 | 4/6 (66.7%) | 11 | 3/5 (60%) | 4 | 3/4 (75%) | 6 | 6/11 (54.5%) | 20 | 10/16 (62.5%) | 15 | 5/6 (83.3%) | 14 | 3/4 (75%) | 7 | 5/7 (71.4%) | 9 | 3/6 (50%) | 3 | 8/10 (80%) | 11 | 8/14 (57.1%) | 29 | 3/4 (75%) | 5 | 2/4 (50%) | 3 | 3/4 (75%) | 6 | 18/26 (69.2%) | 40 | 7/12 (58.3%) | 15 | |
| Feeling cold | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 1/10 (10%) | 1 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 | |||
| Gait disturbance | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 1/6 (16.7%) | 1 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 1/4 (25%) | 1 | 1/4 (25%) | 1 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 | |||
| Hernia pain | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 1/8 (12.5%) | 1 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 | |||
| Influenza like illness | 0/3 (0%) | 1/3 (33.3%) | 1 | 0/3 (0%) | 1 | 0/6 (0%) | 0 | 1/8 (12.5%) | 1 | 0/3 (0%) | 0 | 1/10 (10%) | 1 | 0/3 (0%) | 0 | 1/4 (25%) | 1 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 3/13 (23.1%) | 5 | 1/6 (16.7%) | 1 | 3/5 (60%) | 4 | 0/4 (0%) | 0 | 1/11 (9.1%) | 2 | 2/16 (12.5%) | 2 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 1/10 (10%) | 1 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 2/26 (7.7%) | 2 | 0/12 (0%) | 0 | |
| Local swelling | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/6 (16.7%) | 1 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 1/6 (16.7%) | 1 | 0/13 (0%) | 0 | 1/6 (16.7%) | 1 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 | |||
| Localised oedema | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 1/3 (33.3%) | 1 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 | |||
| Malaise | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 3/8 (37.5%) | 3 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 4/13 (30.8%) | 4 | 0/6 (0%) | 0 | 1/5 (20%) | 1 | 0/4 (0%) | 0 | 1/11 (9.1%) | 1 | 3/16 (18.8%) | 3 | 0/6 (0%) | 0 | 1/4 (25%) | 1 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 1/4 (25%) | 1 | 0/4 (0%) | 0 | 2/4 (50%) | 2 | 4/26 (15.4%) | 5 | 5/12 (41.7%) | 6 | |||
| Mucosal inflammation | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 2/13 (15.4%) | 2 | 1/6 (16.7%) | 1 | 1/5 (20%) | 1 | 0/4 (0%) | 0 | 1/11 (9.1%) | 1 | 0/16 (0%) | 0 | 1/6 (16.7%) | 2 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 | |||
| Non-cardiac chest pain | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/6 (16.7%) | 1 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 1/10 (10%) | 1 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 1/11 (9.1%) | 1 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 1/7 (14.3%) | 1 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/26 (3.8%) | 1 | 0/12 (0%) | 0 | |||
| Oedema peripheral | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 2/10 (20%) | 3 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 1/6 (16.7%) | 4 | 6/13 (46.2%) | 6 | 3/6 (50%) | 3 | 1/5 (20%) | 1 | 1/4 (25%) | 3 | 2/11 (18.2%) | 2 | 2/16 (12.5%) | 2 | 2/6 (33.3%) | 3 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 1/6 (16.7%) | 1 | 2/10 (20%) | 2 | 1/14 (7.1%) | 1 | 2/4 (50%) | 2 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 1/12 (8.3%) | 1 | |||
| Pain | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 1/8 (12.5%) | 1 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 1/9 (11.1%) | 1 | 0/6 (0%) | 0 | 1/13 (7.7%) | 1 | 2/6 (33.3%) | 4 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 1/11 (9.1%) | 3 | 1/16 (6.3%) | 2 | 1/6 (16.7%) | 1 | 0/4 (0%) | 0 | 1/7 (14.3%) | 1 | 0/6 (0%) | 0 | 1/10 (10%) | 1 | 1/14 (7.1%) | 1 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/26 (3.8%) | 1 | 1/12 (8.3%) | 1 | |||
| Pyrexia | 0/3 (0%) | 1/3 (33.3%) | 1 | 0/3 (0%) | 1 | 3/6 (50%) | 7 | 3/8 (37.5%) | 5 | 2/3 (66.7%) | 2 | 0/10 (0%) | 0 | 1/3 (33.3%) | 3 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 2/6 (33.3%) | 13 | 3/13 (23.1%) | 10 | 5/6 (83.3%) | 14 | 1/5 (20%) | 2 | 3/4 (75%) | 5 | 5/11 (45.5%) | 9 | 4/16 (25%) | 10 | 4/6 (66.7%) | 9 | 1/4 (25%) | 1 | 1/7 (14.3%) | 1 | 4/6 (66.7%) | 5 | 2/10 (20%) | 2 | 2/14 (14.3%) | 2 | 0/4 (0%) | 0 | 1/4 (25%) | 1 | 1/4 (25%) | 1 | 8/26 (30.8%) | 11 | 2/12 (16.7%) | 4 | |
| Hepatobiliary disorders | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Hepatic pain | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 1/6 (16.7%) | 1 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 | |||
| Hepatitis | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 1/13 (7.7%) | 1 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 | |||
| Hepatotoxicity | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 2/8 (25%) | 4 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 | |||
| Hyperbilirubinaemia | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 1/9 (11.1%) | 1 | 1/6 (16.7%) | 1 | 1/13 (7.7%) | 1 | 0/6 (0%) | 0 | 1/5 (20%) | 1 | 0/4 (0%) | 0 | 1/11 (9.1%) | 2 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/26 (3.8%) | 1 | 0/12 (0%) | 0 | |||
| Immune system disorders | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Drug hypersensitivity | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 1/9 (11.1%) | 1 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 1/16 (6.3%) | 1 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 1/6 (16.7%) | 1 | 1/10 (10%) | 1 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 3/26 (11.5%) | 3 | 1/12 (8.3%) | 1 | |||
| Hypersensitivity | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/4 (25%) | 1 | 0/26 (0%) | 0 | 0/12 (0%) | 0 | |||
| Seasonal allergy | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 1/5 (20%) | 1 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 | |||
| Infections and infestations | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cellulitis | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/6 (16.7%) | 2 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 2/6 (33.3%) | 4 | 0/5 (0%) | 0 | 1/4 (25%) | 1 | 3/11 (27.3%) | 8 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 | |||
| Cystitis | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 1/6 (16.7%) | 1 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/26 (3.8%) | 2 | 0/12 (0%) | 0 | |||
| Diverticulitis | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 1/5 (20%) | 1 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 | |||
| Gastroenteritis viral | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 1/3 (33.3%) | 1 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 1/5 (20%) | 1 | 0/4 (0%) | 0 | 1/11 (9.1%) | 1 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 | |||
| Gastrointestinal infection | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 1/16 (6.3%) | 1 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 | |||
| Herpes virus infection | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 1/9 (11.1%) | 1 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 | |||
| Herpes zoster | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/6 (16.7%) | 1 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 1/4 (25%) | 1 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 1/7 (14.3%) | 1 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 | |||
| Infection | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 1/4 (25%) | 1 | 0/11 (0%) | 0 | 1/16 (6.3%) | 1 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 1/14 (7.1%) | 1 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 | |||
| Influenza | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/4 (25%) | 1 | 0/26 (0%) | 0 | 0/12 (0%) | 0 | |||
| Nasopharyngitis | 0/3 (0%) | 1/3 (33.3%) | 1 | 0/3 (0%) | 1 | 0/6 (0%) | 0 | 1/8 (12.5%) | 1 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 1/5 (20%) | 1 | 0/4 (0%) | 0 | 2/11 (18.2%) | 3 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 2/4 (50%) | 3 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 1/10 (10%) | 1 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 2/26 (7.7%) | 2 | 1/12 (8.3%) | 2 | |
| Oral candidiasis | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 1/8 (12.5%) | 1 | 0/3 (0%) | 0 | 1/10 (10%) | 1 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/26 (3.8%) | 1 | 0/12 (0%) | 0 | |||
| Periodontitis | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 1/6 (16.7%) | 1 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 | |||
| Pneumonia | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/6 (16.7%) | 1 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 1/11 (9.1%) | 1 | 2/16 (12.5%) | 2 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 1/12 (8.3%) | 2 | |||
| Postoperative wound infection | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 1/12 (8.3%) | 1 | |||
| Rhinitis | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 1/6 (16.7%) | 1 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 2/11 (18.2%) | 3 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/26 (3.8%) | 1 | 0/12 (0%) | 0 | |||
| Sinusitis | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 1/11 (9.1%) | 2 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 1/4 (25%) | 1 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 | |||
| Skin infection | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/6 (16.7%) | 1 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 1/6 (16.7%) | 2 | 0/13 (0%) | 0 | 1/6 (16.7%) | 1 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/26 (3.8%) | 1 | 0/12 (0%) | 0 | |||
| Upper respiratory tract infection | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 1/10 (10%) | 1 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 1/11 (9.1%) | 1 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 1/6 (16.7%) | 1 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/26 (3.8%) | 1 | 0/12 (0%) | 0 | |||
| Urinary tract infection | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 1/6 (16.7%) | 1 | 1/5 (20%) | 1 | 0/4 (0%) | 0 | 1/11 (9.1%) | 1 | 1/16 (6.3%) | 1 | 1/6 (16.7%) | 1 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 1/6 (16.7%) | 1 | 0/10 (0%) | 0 | 2/14 (14.3%) | 2 | 1/4 (25%) | 1 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 | |||
| Wound infection | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 1/11 (9.1%) | 1 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 | |||
| Injury, poisoning and procedural complications | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Contusion | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 1/9 (11.1%) | 1 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 | |||
| Excoriation | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 1/11 (9.1%) | 1 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 1/7 (14.3%) | 1 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/4 (25%) | 1 | 1/26 (3.8%) | 1 | 0/12 (0%) | 0 | |||
| Fall | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 1/13 (7.7%) | 1 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 1/11 (9.1%) | 2 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 1/4 (25%) | 1 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 | |||
| Infusion related reaction | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 1/14 (7.1%) | 3 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 | |||
| Ligament sprain | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 1/6 (16.7%) | 1 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 1/11 (9.1%) | 1 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 | |||
| Pelvic fracture | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 1/11 (9.1%) | 1 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 | |||
| Periorbital haemorrhage | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 1/6 (16.7%) | 1 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 | |||
| Post procedural complication | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 1/9 (11.1%) | 1 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 | |||
| Postoperative wound complication | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 1/6 (16.7%) | 1 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 | |||
| Procedural pain | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 1/9 (11.1%) | 1 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 3/26 (11.5%) | 3 | 0/12 (0%) | 0 | |||
| Transfusion reaction | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 1/14 (7.1%) | 1 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 | |||
| Wound | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 1/6 (16.7%) | 2 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 | |||
| Investigations | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Activated partial thromboplastin time prolonged | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 1/9 (11.1%) | 1 | 0/6 (0%) | 0 | 1/13 (7.7%) | 2 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 | |||
| Alanine aminotransferase decreased | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 1/14 (7.1%) | 1 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 | |||
| Alanine aminotransferase increased | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 2/6 (33.3%) | 3 | 2/8 (25%) | 2 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 3/6 (50%) | 10 | 1/13 (7.7%) | 1 | 1/6 (16.7%) | 6 | 3/5 (60%) | 3 | 2/4 (50%) | 2 | 1/11 (9.1%) | 2 | 1/16 (6.3%) | 1 | 3/6 (50%) | 5 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 4/14 (28.6%) | 8 | 1/4 (25%) | 6 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 | |||
| Aspartate aminotransferase decreased | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 1/14 (7.1%) | 1 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 | |||
| Aspartate aminotransferase increased | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 2/6 (33.3%) | 3 | 2/8 (25%) | 2 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 3/6 (50%) | 7 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 1/5 (20%) | 1 | 2/4 (50%) | 2 | 1/11 (9.1%) | 3 | 1/16 (6.3%) | 1 | 1/6 (16.7%) | 2 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 3/14 (21.4%) | 3 | 1/4 (25%) | 3 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 | |||
| Blood alkaline phosphatase increased | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 1/9 (11.1%) | 1 | 0/6 (0%) | 0 | 1/13 (7.7%) | 1 | 0/6 (0%) | 0 | 1/5 (20%) | 4 | 1/4 (25%) | 1 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 1/6 (16.7%) | 1 | 1/10 (10%) | 1 | 0/14 (0%) | 0 | 1/4 (25%) | 1 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 2/26 (7.7%) | 2 | 0/12 (0%) | 0 | |||
| Blood bicarbonate decreased | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 1/6 (16.7%) | 1 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 | |||
| Blood bilirubin increased | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 1/6 (16.7%) | 1 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 | |||
| Blood creatinine increased | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 3/10 (30%) | 5 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 1/6 (16.7%) | 1 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 2/11 (18.2%) | 2 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 1/6 (16.7%) | 2 | 2/10 (20%) | 3 | 4/14 (28.6%) | 12 | 2/4 (50%) | 3 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 | |||
| Blood lactate dehydrogenase increased | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 1/14 (7.1%) | 1 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 | |||
| Blood magnesium decreased | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 1/10 (10%) | 1 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 | |||
| Blood potassium decreased | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 1/14 (7.1%) | 2 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 | |||
| Blood urea increased | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 1/12 (8.3%) | 1 | |||
| Body temperature increased | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/6 (16.7%) | 1 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 | |||
| Breath sounds abnormal | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 1/10 (10%) | 1 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 | |||
| Lymphocyte count decreased | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 1/16 (6.3%) | 1 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 | |||
| Neutrophil count decreased | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 3/13 (23.1%) | 4 | 0/6 (0%) | 0 | 1/5 (20%) | 1 | 1/4 (25%) | 1 | 1/11 (9.1%) | 1 | 1/16 (6.3%) | 3 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 1/7 (14.3%) | 1 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 2/14 (14.3%) | 2 | 3/4 (75%) | 7 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/26 (3.8%) | 1 | 1/12 (8.3%) | 4 | |||
| Platelet count decreased | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 1/16 (6.3%) | 3 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 1/4 (25%) | 1 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/26 (3.8%) | 1 | 0/12 (0%) | 0 | |||
| Weight decreased | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/6 (16.7%) | 1 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 1/6 (16.7%) | 1 | 1/13 (7.7%) | 1 | 1/6 (16.7%) | 1 | 1/5 (20%) | 1 | 1/4 (25%) | 1 | 1/11 (9.1%) | 1 | 1/16 (6.3%) | 1 | 1/6 (16.7%) | 1 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 1/6 (16.7%) | 1 | 2/10 (20%) | 2 | 1/14 (7.1%) | 2 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/26 (3.8%) | 1 | 1/12 (8.3%) | 1 | |||
| White blood cell count decreased | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 1/13 (7.7%) | 1 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 1/16 (6.3%) | 2 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/26 (3.8%) | 1 | 0/12 (0%) | 0 | |||
| Metabolism and nutrition disorders | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Decreased appetite | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 3/6 (50%) | 3 | 1/8 (12.5%) | 1 | 1/3 (33.3%) | 1 | 1/10 (10%) | 1 | 1/3 (33.3%) | 1 | 0/4 (0%) | 0 | 1/9 (11.1%) | 1 | 1/6 (16.7%) | 2 | 4/13 (30.8%) | 4 | 3/6 (50%) | 4 | 1/5 (20%) | 1 | 2/4 (50%) | 2 | 3/11 (27.3%) | 3 | 3/16 (18.8%) | 3 | 3/6 (50%) | 4 | 2/4 (50%) | 2 | 3/7 (42.9%) | 5 | 2/6 (33.3%) | 2 | 2/10 (20%) | 2 | 3/14 (21.4%) | 5 | 1/4 (25%) | 1 | 0/4 (0%) | 0 | 1/4 (25%) | 1 | 6/26 (23.1%) | 7 | 1/12 (8.3%) | 1 | |||
| Dehydration | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 1/8 (12.5%) | 1 | 0/3 (0%) | 0 | 2/10 (20%) | 5 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 2/9 (22.2%) | 2 | 1/6 (16.7%) | 1 | 1/13 (7.7%) | 1 | 1/6 (16.7%) | 1 | 1/5 (20%) | 1 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 1/16 (6.3%) | 3 | 2/6 (33.3%) | 2 | 0/4 (0%) | 0 | 1/7 (14.3%) | 1 | 0/6 (0%) | 0 | 2/10 (20%) | 2 | 1/14 (7.1%) | 4 | 2/4 (50%) | 4 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 2/12 (16.7%) | 2 | |||
| Electrolyte imbalance | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 1/12 (8.3%) | 1 | |||
| Fluid overload | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 1/4 (25%) | 1 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 | |||
| Hyperalbuminaemia | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 1/4 (25%) | 1 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 | |||
| Hypercalcaemia | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 1/9 (11.1%) | 1 | 1/6 (16.7%) | 1 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 1/16 (6.3%) | 2 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 | |||
| Hyperglycaemia | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 1/8 (12.5%) | 1 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 1/9 (11.1%) | 1 | 1/6 (16.7%) | 1 | 3/13 (23.1%) | 4 | 0/6 (0%) | 0 | 1/5 (20%) | 2 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 2/10 (20%) | 2 | 1/14 (7.1%) | 1 | 2/4 (50%) | 2 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/26 (3.8%) | 1 | 1/12 (8.3%) | 1 | |||
| Hyperkalaemia | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 1/6 (16.7%) | 1 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 1/5 (20%) | 1 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 1/16 (6.3%) | 1 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 1/14 (7.1%) | 2 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/26 (3.8%) | 1 | 1/12 (8.3%) | 2 | |||
| Hyperphosphataemia | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 1/5 (20%) | 1 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 | |||
| Hyperuricaemia | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 1/11 (9.1%) | 1 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 1/14 (7.1%) | 1 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 | |||
| Hypoalbuminaemia | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 1/8 (12.5%) | 1 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 3/13 (23.1%) | 3 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 1/10 (10%) | 1 | 1/14 (7.1%) | 1 | 2/4 (50%) | 2 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 2/26 (7.7%) | 2 | 0/12 (0%) | 0 | |||
| Hypocalcaemia | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/6 (16.7%) | 1 | 1/8 (12.5%) | 1 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 1/13 (7.7%) | 1 | 0/6 (0%) | 0 | 1/5 (20%) | 1 | 1/4 (25%) | 1 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 1/14 (7.1%) | 1 | 3/4 (75%) | 4 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/26 (3.8%) | 1 | 1/12 (8.3%) | 1 | |||
| Hypokalaemia | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 1/8 (12.5%) | 1 | 0/3 (0%) | 0 | 3/10 (30%) | 4 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 1/9 (11.1%) | 1 | 1/6 (16.7%) | 1 | 3/13 (23.1%) | 4 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 1/4 (25%) | 1 | 1/11 (9.1%) | 1 | 1/16 (6.3%) | 1 | 1/6 (16.7%) | 2 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 2/6 (33.3%) | 2 | 1/10 (10%) | 1 | 1/14 (7.1%) | 1 | 3/4 (75%) | 5 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 4/26 (15.4%) | 5 | 0/12 (0%) | 0 | |||
| Hypomagnesaemia | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 1/8 (12.5%) | 1 | 0/3 (0%) | 0 | 2/10 (20%) | 3 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 2/9 (22.2%) | 4 | 0/6 (0%) | 0 | 2/13 (15.4%) | 2 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 1/4 (25%) | 1 | 1/11 (9.1%) | 1 | 2/16 (12.5%) | 2 | 1/6 (16.7%) | 1 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 1/6 (16.7%) | 1 | 4/10 (40%) | 4 | 2/14 (14.3%) | 2 | 3/4 (75%) | 4 | 0/4 (0%) | 0 | 1/4 (25%) | 1 | 2/26 (7.7%) | 2 | 2/12 (16.7%) | 4 | |||
| Hyponatraemia | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 2/13 (15.4%) | 2 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 1/11 (9.1%) | 1 | 2/16 (12.5%) | 3 | 1/6 (16.7%) | 2 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 1/10 (10%) | 1 | 1/14 (7.1%) | 3 | 2/4 (50%) | 5 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/26 (3.8%) | 7 | 2/12 (16.7%) | 3 | |||
| Hypophosphataemia | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 3/9 (33.3%) | 5 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 1/4 (25%) | 1 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 1/6 (16.7%) | 1 | 2/10 (20%) | 2 | 1/14 (7.1%) | 1 | 1/4 (25%) | 2 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 | |||
| Musculoskeletal and connective tissue disorders | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Arthralgia | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 2/6 (33.3%) | 2 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 2/9 (22.2%) | 3 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 1/6 (16.7%) | 1 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 1/10 (10%) | 1 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/4 (25%) | 1 | 2/26 (7.7%) | 3 | 1/12 (8.3%) | 3 | |||
| Arthritis | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 1/6 (16.7%) | 1 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 | |||
| Back pain | 0/3 (0%) | 1/3 (33.3%) | 1 | 0/3 (0%) | 1 | 2/6 (33.3%) | 3 | 1/8 (12.5%) | 1 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 3/6 (50%) | 4 | 1/13 (7.7%) | 4 | 1/6 (16.7%) | 1 | 2/5 (40%) | 3 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 3/16 (18.8%) | 3 | 2/6 (33.3%) | 2 | 0/4 (0%) | 0 | 1/7 (14.3%) | 2 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 3/14 (21.4%) | 3 | 0/4 (0%) | 0 | 2/4 (50%) | 3 | 0/4 (0%) | 0 | 2/26 (7.7%) | 2 | 3/12 (25%) | 3 | |
| Bone pain | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 1/11 (9.1%) | 1 | 0/16 (0%) | 0 | 1/6 (16.7%) | 1 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 | |||
| Bursitis | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 1/16 (6.3%) | 1 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 | |||
| Finger deformity | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 1/13 (7.7%) | 1 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 | |||
| Flank pain | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 1/6 (16.7%) | 1 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 1/10 (10%) | 1 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 1/12 (8.3%) | 1 | |||
| Gouty arthritis | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 1/6 (16.7%) | 1 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 | |||
| Groin pain | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 1/10 (10%) | 1 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 1/6 (16.7%) | 2 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 1/11 (9.1%) | 1 | 0/16 (0%) | 0 | 1/6 (16.7%) | 1 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 | |||
| Joint swelling | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 1/6 (16.7%) | 2 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 1/11 (9.1%) | 1 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 | |||
| Limb discomfort | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 1/11 (9.1%) | 1 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 | |||
| Muscle spasms | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/6 (16.7%) | 1 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 2/10 (20%) | 3 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 1/9 (11.1%) | 1 | 0/6 (0%) | 0 | 1/13 (7.7%) | 2 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 1/11 (9.1%) | 2 | 1/16 (6.3%) | 1 | 1/6 (16.7%) | 1 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 1/10 (10%) | 1 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/4 (25%) | 1 | 1/26 (3.8%) | 1 | 0/12 (0%) | 0 | |||
| Muscle twitching | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 1/11 (9.1%) | 1 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 | |||
| Muscular weakness | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 1/6 (16.7%) | 1 | 1/13 (7.7%) | 1 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 1/4 (25%) | 1 | 1/11 (9.1%) | 2 | 1/16 (6.3%) | 1 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 1/14 (7.1%) | 3 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 | |||
| Musculoskeletal chest pain | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 2/9 (22.2%) | 2 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 1/6 (16.7%) | 1 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 1/10 (10%) | 1 | 1/14 (7.1%) | 1 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 | |||
| Musculoskeletal discomfort | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 1/6 (16.7%) | 1 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 1/12 (8.3%) | 1 | |||
| Musculoskeletal pain | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 1/10 (10%) | 1 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 1/9 (11.1%) | 1 | 1/6 (16.7%) | 1 | 1/13 (7.7%) | 4 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 1/11 (9.1%) | 2 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 3/7 (42.9%) | 3 | 0/6 (0%) | 0 | 1/10 (10%) | 1 | 1/14 (7.1%) | 1 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/26 (3.8%) | 1 | 0/12 (0%) | 0 | |||
| Musculoskeletal stiffness | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 1/16 (6.3%) | 1 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 | |||
| Myalgia | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 1/8 (12.5%) | 1 | 1/3 (33.3%) | 1 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 3/13 (23.1%) | 5 | 1/6 (16.7%) | 2 | 1/5 (20%) | 1 | 1/4 (25%) | 1 | 1/11 (9.1%) | 1 | 2/16 (12.5%) | 2 | 1/6 (16.7%) | 1 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/4 (25%) | 1 | 3/26 (11.5%) | 7 | 1/12 (8.3%) | 1 | |||
| Neck pain | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 1/6 (16.7%) | 1 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 1/4 (25%) | 1 | 1/11 (9.1%) | 1 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 | |||
| Pain in extremity | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/6 (16.7%) | 1 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 2/10 (20%) | 2 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 2/6 (33.3%) | 6 | 3/13 (23.1%) | 3 | 2/6 (33.3%) | 3 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 1/11 (9.1%) | 1 | 1/16 (6.3%) | 2 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 1/10 (10%) | 1 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/4 (25%) | 1 | 2/26 (7.7%) | 2 | 1/12 (8.3%) | 3 | |||
| Pain in jaw | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 1/6 (16.7%) | 1 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 | |||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Tumour pain | 1/3 (33.3%) | 2 | 0/3 (0%) | 2 | 0/3 (0%) | 2 | 0/6 (0%) | 2 | 0/8 (0%) | 2 | 0/3 (0%) | 2 | 0/10 (0%) | 2 | 0/3 (0%) | 2 | 0/4 (0%) | 2 | 0/9 (0%) | 2 | 0/6 (0%) | 2 | 0/13 (0%) | 2 | 0/6 (0%) | 2 | 0/5 (0%) | 2 | 0/4 (0%) | 2 | 0/11 (0%) | 2 | 0/16 (0%) | 2 | 0/6 (0%) | 2 | 0/4 (0%) | 2 | 0/7 (0%) | 2 | 0/6 (0%) | 2 | 0/10 (0%) | 2 | 0/14 (0%) | 2 | 0/4 (0%) | 2 | 0/4 (0%) | 2 | 0/4 (0%) | 2 | 0/26 (0%) | 2 | 0/12 (0%) | 2 |
| Neoplasm | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 1/16 (6.3%) | 1 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 | |||
| Seborrhoeic keratosis | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 1/7 (14.3%) | 1 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 | |||
| Nervous system disorders | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Amnesia | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 1/10 (10%) | 1 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 | |||
| Asterixis | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 1/11 (9.1%) | 2 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 | |||
| Balance disorder | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 1/12 (8.3%) | 1 | |||
| Burning sensation | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 1/6 (16.7%) | 1 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 1/12 (8.3%) | 1 | |||
| Cognitive disorder | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 1/6 (16.7%) | 1 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 1/10 (10%) | 2 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 | |||
| Dizziness | 1/3 (33.3%) | 1 | 0/3 (0%) | 1 | 0/3 (0%) | 1 | 2/6 (33.3%) | 2 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 2/10 (20%) | 3 | 0/3 (0%) | 0 | 1/4 (25%) | 1 | 2/9 (22.2%) | 2 | 0/6 (0%) | 0 | 2/13 (15.4%) | 2 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 1/16 (6.3%) | 1 | 0/6 (0%) | 0 | 1/4 (25%) | 1 | 1/7 (14.3%) | 1 | 1/6 (16.7%) | 1 | 0/10 (0%) | 0 | 3/14 (21.4%) | 4 | 2/4 (50%) | 2 | 1/4 (25%) | 2 | 1/4 (25%) | 1 | 4/26 (15.4%) | 6 | 4/12 (33.3%) | 4 |
| Dysgeusia | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 1/13 (7.7%) | 1 | 1/6 (16.7%) | 1 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 1/11 (9.1%) | 1 | 1/16 (6.3%) | 2 | 1/6 (16.7%) | 1 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 1/10 (10%) | 1 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/26 (3.8%) | 2 | 1/12 (8.3%) | 1 | |||
| Head discomfort | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 1/9 (11.1%) | 1 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 | |||
| Headache | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 3/8 (37.5%) | 3 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 1/4 (25%) | 1 | 1/9 (11.1%) | 1 | 1/6 (16.7%) | 1 | 5/13 (38.5%) | 6 | 2/6 (33.3%) | 3 | 1/5 (20%) | 2 | 1/4 (25%) | 2 | 3/11 (27.3%) | 15 | 2/16 (12.5%) | 2 | 2/6 (33.3%) | 2 | 1/4 (25%) | 1 | 2/7 (28.6%) | 2 | 0/6 (0%) | 0 | 2/10 (20%) | 2 | 3/14 (21.4%) | 4 | 0/4 (0%) | 0 | 1/4 (25%) | 1 | 1/4 (25%) | 1 | 4/26 (15.4%) | 4 | 2/12 (16.7%) | 3 | |||
| Horner's syndrome | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 1/11 (9.1%) | 1 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 | |||
| Hyperaesthesia | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 1/12 (8.3%) | 1 | |||
| Hypoaesthesia | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 1/13 (7.7%) | 2 | 1/6 (16.7%) | 1 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 1/6 (16.7%) | 1 | 0/10 (0%) | 0 | 1/14 (7.1%) | 1 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 | |||
| Memory impairment | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 1/4 (25%) | 1 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 1/14 (7.1%) | 1 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 | |||
| Neuropathy peripheral | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/6 (16.7%) | 1 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 1/10 (10%) | 1 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 1/6 (16.7%) | 1 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 3/5 (60%) | 4 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 2/16 (12.5%) | 2 | 2/6 (33.3%) | 2 | 0/4 (0%) | 0 | 1/7 (14.3%) | 1 | 0/6 (0%) | 0 | 2/10 (20%) | 2 | 0/14 (0%) | 0 | 2/4 (50%) | 2 | 1/4 (25%) | 1 | 0/4 (0%) | 0 | 6/26 (23.1%) | 7 | 4/12 (33.3%) | 5 | |||
| Paraesthesia | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/6 (16.7%) | 1 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 1/9 (11.1%) | 1 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 2/6 (33.3%) | 3 | 1/5 (20%) | 1 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 1/6 (16.7%) | 1 | 1/10 (10%) | 1 | 1/14 (7.1%) | 1 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 | |||
| Peripheral motor neuropathy | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 1/10 (10%) | 1 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 | |||
| Peripheral sensory neuropathy | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 1/6 (16.7%) | 1 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 1/7 (14.3%) | 1 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 1/14 (7.1%) | 1 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/4 (25%) | 1 | 0/26 (0%) | 0 | 0/12 (0%) | 0 | |||
| Restless legs syndrome | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 1/16 (6.3%) | 1 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 | |||
| Sinus headache | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 1/11 (9.1%) | 3 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 | |||
| Somnolence | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 1/10 (10%) | 1 | 1/14 (7.1%) | 1 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 | |||
| Speech disorder | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 1/5 (20%) | 1 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 | |||
| Syncope | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 1/3 (33.3%) | 2 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 1/10 (10%) | 1 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 2/26 (7.7%) | 2 | 1/12 (8.3%) | 1 | |||
| Transient ischaemic attack | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 1/10 (10%) | 1 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 | |||
| Psychiatric disorders | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Agitation | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 1/10 (10%) | 1 | 1/14 (7.1%) | 1 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 | |||
| Anxiety | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 1/13 (7.7%) | 1 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 1/4 (25%) | 1 | 0/11 (0%) | 0 | 1/16 (6.3%) | 1 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 1/10 (10%) | 1 | 1/14 (7.1%) | 2 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 | |||
| Anxiety disorder | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 1/6 (16.7%) | 1 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 | |||
| Confusional state | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 1/8 (12.5%) | 1 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 1/9 (11.1%) | 1 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 2/11 (18.2%) | 3 | 1/16 (6.3%) | 1 | 1/6 (16.7%) | 1 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/26 (3.8%) | 1 | 0/12 (0%) | 0 | |||
| Delusion | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 1/3 (33.3%) | 1 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 | |||
| Depression | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 1/9 (11.1%) | 1 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 1/6 (16.7%) | 1 | 0/5 (0%) | 0 | 1/4 (25%) | 1 | 1/11 (9.1%) | 1 | 1/16 (6.3%) | 2 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 | |||
| Insomnia | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 1/10 (10%) | 1 | 1/3 (33.3%) | 1 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 2/5 (40%) | 2 | 0/4 (0%) | 0 | 1/11 (9.1%) | 1 | 1/16 (6.3%) | 1 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 1/7 (14.3%) | 1 | 2/6 (33.3%) | 2 | 2/10 (20%) | 2 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 1/12 (8.3%) | 1 | |||
| Renal and urinary disorders | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Bladder spasm | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 1/16 (6.3%) | 1 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 | |||
| Dysuria | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 1/8 (12.5%) | 1 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 2/6 (33.3%) | 2 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 1/14 (7.1%) | 1 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/26 (3.8%) | 1 | 0/12 (0%) | 0 | |||
| Haematuria | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 1/6 (16.7%) | 1 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 1/12 (8.3%) | 1 | |||
| Hydronephrosis | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 1/6 (16.7%) | 1 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 | |||
| Nephropathy | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 1/14 (7.1%) | 1 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 | |||
| Neurogenic bladder | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 1/11 (9.1%) | 1 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 | |||
| Nocturia | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 2/6 (33.3%) | 3 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 | |||
| Pollakiuria | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 1/9 (11.1%) | 1 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 1/4 (25%) | 1 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/26 (3.8%) | 1 | 1/12 (8.3%) | 1 | |||
| Renal failure acute | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 1/10 (10%) | 1 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 | |||
| Renal impairment | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 2/10 (20%) | 2 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/26 (3.8%) | 1 | 0/12 (0%) | 0 | |||
| Urinary hesitation | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 1/11 (9.1%) | 1 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 | |||
| Urinary incontinence | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 1/13 (7.7%) | 1 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 1/6 (16.7%) | 1 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 | |||
| Urinary retention | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 1/9 (11.1%) | 1 | 0/6 (0%) | 0 | 1/13 (7.7%) | 1 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 | |||
| Urinary tract obstruction | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 1/10 (10%) | 1 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 | |||
| Urinary tract pain | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 1/11 (9.1%) | 1 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 | |||
| Reproductive system and breast disorders | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Breast pain | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 1/6 (16.7%) | 1 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 | |||
| Female genital tract fistula | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 1/6 (16.7%) | 1 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 | |||
| Pelvic pain | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 1/10 (10%) | 1 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 | |||
| Scrotal oedema | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 1/3 (33.3%) | 1 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 | |||
| Scrotal swelling | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 1/11 (9.1%) | 1 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 | |||
| Vulvovaginal pain | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 1/16 (6.3%) | 1 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 | |||
| Vulvovaginal pruritus | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 1/8 (12.5%) | 1 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 | |||
| Respiratory, thoracic and mediastinal disorders | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Bronchospasm | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 1/13 (7.7%) | 1 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 | |||
| Cough | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/6 (16.7%) | 1 | 2/8 (25%) | 3 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 1/9 (11.1%) | 2 | 1/6 (16.7%) | 1 | 2/13 (15.4%) | 2 | 1/6 (16.7%) | 2 | 1/5 (20%) | 1 | 1/4 (25%) | 1 | 2/11 (18.2%) | 3 | 1/16 (6.3%) | 1 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 1/7 (14.3%) | 1 | 0/6 (0%) | 0 | 2/10 (20%) | 2 | 3/14 (21.4%) | 3 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/4 (25%) | 1 | 5/26 (19.2%) | 6 | 4/12 (33.3%) | 4 | |||
| Diaphragmalgia | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 1/13 (7.7%) | 1 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 1/16 (6.3%) | 1 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 | |||
| Dysphonia | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 2/13 (15.4%) | 3 | 1/6 (16.7%) | 1 | 1/5 (20%) | 1 | 1/4 (25%) | 1 | 2/11 (18.2%) | 2 | 1/16 (6.3%) | 1 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 1/10 (10%) | 1 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 2/26 (7.7%) | 2 | 0/12 (0%) | 0 | |||
| Dyspnoea | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/6 (16.7%) | 1 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 1/3 (33.3%) | 1 | 1/4 (25%) | 1 | 0/9 (0%) | 0 | 2/6 (33.3%) | 2 | 3/13 (23.1%) | 3 | 1/6 (16.7%) | 1 | 2/5 (40%) | 2 | 4/4 (100%) | 6 | 0/11 (0%) | 0 | 1/16 (6.3%) | 1 | 3/6 (50%) | 3 | 2/4 (50%) | 2 | 2/7 (28.6%) | 2 | 1/6 (16.7%) | 1 | 3/10 (30%) | 3 | 2/14 (14.3%) | 3 | 2/4 (50%) | 2 | 1/4 (25%) | 1 | 2/4 (50%) | 2 | 3/26 (11.5%) | 3 | 3/12 (25%) | 4 | |||
| Dyspnoea exertional | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 1/8 (12.5%) | 1 | 0/3 (0%) | 0 | 1/10 (10%) | 1 | 0/3 (0%) | 0 | 1/4 (25%) | 1 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 1/13 (7.7%) | 1 | 0/6 (0%) | 0 | 1/5 (20%) | 1 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 3/26 (11.5%) | 5 | 0/12 (0%) | 0 | |||
| Epistaxis | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/6 (16.7%) | 1 | 0/8 (0%) | 0 | 1/3 (33.3%) | 1 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 1/6 (16.7%) | 1 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 1/11 (9.1%) | 1 | 0/16 (0%) | 0 | 1/6 (16.7%) | 1 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/4 (25%) | 1 | 1/26 (3.8%) | 1 | 1/12 (8.3%) | 2 | |||
| Haemoptysis | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 1/13 (7.7%) | 1 | 0/6 (0%) | 0 | 1/5 (20%) | 1 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 1/16 (6.3%) | 1 | 1/6 (16.7%) | 1 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 | |||
| Hiccups | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 1/10 (10%) | 1 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 2/6 (33.3%) | 4 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 1/6 (16.7%) | 1 | 0/4 (0%) | 0 | 1/7 (14.3%) | 1 | 1/6 (16.7%) | 2 | 0/10 (0%) | 0 | 1/14 (7.1%) | 1 | 1/4 (25%) | 1 | 0/4 (0%) | 0 | 1/4 (25%) | 2 | 2/26 (7.7%) | 2 | 3/12 (25%) | 3 | |||
| Hypoxia | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 1/13 (7.7%) | 1 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 | |||
| Nasal congestion | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/6 (16.7%) | 1 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 1/9 (11.1%) | 1 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 1/5 (20%) | 1 | 0/4 (0%) | 0 | 1/11 (9.1%) | 1 | 1/16 (6.3%) | 1 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 | |||
| Oropharyngeal pain | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 1/9 (11.1%) | 2 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 2/6 (33.3%) | 2 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 1/11 (9.1%) | 1 | 0/16 (0%) | 0 | 1/6 (16.7%) | 1 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 1/6 (16.7%) | 1 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 2/26 (7.7%) | 2 | 1/12 (8.3%) | 1 | |||
| Painful respiration | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 1/10 (10%) | 1 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 | |||
| Pleural effusion | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 1/13 (7.7%) | 1 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 | |||
| Pleurisy | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 1/10 (10%) | 1 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 | |||
| Productive cough | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 1/12 (8.3%) | 1 | |||
| Pulmonary artery thrombosis | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 1/4 (25%) | 1 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 | |||
| Pulmonary embolism | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 1/13 (7.7%) | 1 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 1/10 (10%) | 1 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/26 (3.8%) | 1 | 0/12 (0%) | 0 | |||
| Pulmonary hypertension | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 1/13 (7.7%) | 1 | 0/6 (0%) | 0 | 1/5 (20%) | 1 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 | |||
| Rhinorrhoea | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 1/13 (7.7%) | 1 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 1/16 (6.3%) | 1 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 1/12 (8.3%) | 1 | |||
| Upper-airway cough syndrome | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 1/6 (16.7%) | 1 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/26 (3.8%) | 1 | 0/12 (0%) | 0 | |||
| Wheezing | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 1/13 (7.7%) | 1 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 1/14 (7.1%) | 1 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/26 (3.8%) | 1 | 1/12 (8.3%) | 1 | |||
| Skin and subcutaneous tissue disorders | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Acne | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 1/6 (16.7%) | 1 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 | |||
| Alopecia | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 2/8 (25%) | 2 | 1/3 (33.3%) | 1 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 1/9 (11.1%) | 1 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 2/6 (33.3%) | 2 | 0/5 (0%) | 0 | 1/4 (25%) | 1 | 3/11 (27.3%) | 4 | 6/16 (37.5%) | 6 | 3/6 (50%) | 4 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 1/10 (10%) | 1 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 1/4 (25%) | 1 | 1/4 (25%) | 1 | 1/26 (3.8%) | 1 | 1/12 (8.3%) | 1 | |||
| Blister | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/6 (16.7%) | 1 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 1/6 (16.7%) | 1 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 | |||
| Decubitus ulcer | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 2/11 (18.2%) | 4 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 | |||
| Dermatitis acneiform | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 1/6 (16.7%) | 2 | 0/13 (0%) | 0 | 1/6 (16.7%) | 2 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 | |||
| Dermatitis allergic | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 1/4 (25%) | 1 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 | |||
| Dermatitis contact | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 1/4 (25%) | 1 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 | |||
| Dry skin | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 1/4 (25%) | 1 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 2/6 (33.3%) | 2 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 1/12 (8.3%) | 1 | |||
| Ecchymosis | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/26 (3.8%) | 1 | 1/12 (8.3%) | 1 | |||
| Erythema | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 1/8 (12.5%) | 1 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 1/6 (16.7%) | 1 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 1/11 (9.1%) | 2 | 0/16 (0%) | 0 | 1/6 (16.7%) | 1 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/26 (3.8%) | 1 | 1/12 (8.3%) | 1 | |||
| Hyperhidrosis | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/6 (16.7%) | 1 | 1/8 (12.5%) | 1 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 1/6 (16.7%) | 1 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 1/10 (10%) | 1 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/26 (3.8%) | 1 | 2/12 (16.7%) | 2 | |||
| Nail disorder | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 1/6 (16.7%) | 1 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 | |||
| Night sweats | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 1/16 (6.3%) | 1 | 1/6 (16.7%) | 1 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 2/26 (7.7%) | 3 | 1/12 (8.3%) | 1 | |||
| Pain of skin | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 1/16 (6.3%) | 1 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 | |||
| Petechiae | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 1/6 (16.7%) | 1 | 0/13 (0%) | 0 | 1/6 (16.7%) | 1 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 1/12 (8.3%) | 1 | |||
| Plantar erythema | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 1/6 (16.7%) | 1 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 | |||
| Pruritus | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 1/6 (16.7%) | 2 | 0/13 (0%) | 0 | 2/6 (33.3%) | 2 | 1/5 (20%) | 1 | 0/4 (0%) | 0 | 3/11 (27.3%) | 3 | 1/16 (6.3%) | 2 | 1/6 (16.7%) | 1 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 1/4 (25%) | 1 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 1/12 (8.3%) | 1 | |||
| Pruritus generalised | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 1/6 (16.7%) | 2 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 | |||
| Purpura | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 1/6 (16.7%) | 1 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 | |||
| Rash | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 2/6 (33.3%) | 2 | 1/8 (12.5%) | 1 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 1/9 (11.1%) | 2 | 2/6 (33.3%) | 2 | 3/13 (23.1%) | 3 | 2/6 (33.3%) | 7 | 1/5 (20%) | 1 | 2/4 (50%) | 2 | 3/11 (27.3%) | 6 | 5/16 (31.3%) | 6 | 2/6 (33.3%) | 3 | 1/4 (25%) | 1 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 1/10 (10%) | 1 | 0/14 (0%) | 0 | 1/4 (25%) | 1 | 1/4 (25%) | 1 | 0/4 (0%) | 0 | 3/26 (11.5%) | 4 | 1/12 (8.3%) | 1 | |||
| Rash generalised | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/6 (16.7%) | 1 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 | |||
| Rash maculo-papular | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 2/13 (15.4%) | 4 | 1/6 (16.7%) | 1 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 1/11 (9.1%) | 1 | 0/16 (0%) | 0 | 2/6 (33.3%) | 6 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 1/10 (10%) | 1 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 | |||
| Rash pruritic | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 2/6 (33.3%) | 2 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/26 (3.8%) | 1 | 0/12 (0%) | 0 | |||
| Skin discolouration | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 1/7 (14.3%) | 1 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 | |||
| Skin haemorrhage | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/6 (16.7%) | 1 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 | |||
| Skin hyperpigmentation | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 1/13 (7.7%) | 1 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 | |||
| Skin ulcer | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 1/11 (9.1%) | 1 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 | |||
| Swelling face | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 1/11 (9.1%) | 1 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 | |||
| Urticaria | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 1/13 (7.7%) | 1 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/26 (3.8%) | 1 | 0/12 (0%) | 0 | |||
| Vascular disorders | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Deep vein thrombosis | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 1/11 (9.1%) | 1 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 | |||
| Flushing | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 1/5 (20%) | 1 | 0/4 (0%) | 0 | 1/11 (9.1%) | 1 | 1/16 (6.3%) | 1 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 1/10 (10%) | 1 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 2/12 (16.7%) | 2 | |||
| Haematoma | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 1/9 (11.1%) | 1 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 1/6 (16.7%) | 1 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/26 (3.8%) | 1 | 0/12 (0%) | 0 | |||
| Hot flush | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 1/6 (16.7%) | 1 | 1/13 (7.7%) | 1 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 1/11 (9.1%) | 1 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 1/14 (7.1%) | 1 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 | |||
| Hypertension | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 3/14 (21.4%) | 4 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/26 (3.8%) | 1 | 0/12 (0%) | 0 | |||
| Hypotension | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 1/13 (7.7%) | 1 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 1/6 (16.7%) | 1 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/26 (3.8%) | 1 | 0/12 (0%) | 0 | |||
| Intra-abdominal haematoma | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 1/9 (11.1%) | 1 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 | |||
| Lymphoedema | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 1/10 (10%) | 1 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 | |||
| Orthostatic hypotension | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 1/12 (8.3%) | 1 | |||
| Peripheral vascular disorder | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 1/10 (10%) | 1 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 | |||
| Phlebitis | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 1/13 (7.7%) | 1 | 2/6 (33.3%) | 2 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 | |||
| Thrombosis | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 1/6 (16.7%) | 1 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 1/14 (7.1%) | 1 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (0%) | 0 | |||
| Vena cava thrombosis | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/13 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 1/6 (16.7%) | 1 | 0/10 (0%) | 0 | 0/14 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/26 (0%) | 0 | 0/12 (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 60 days prior to submission for publication/presentation. Any information identified by the SPONSOR as confidential must be deleted prior to submission. SPONSOR review can be expedited to meet publication timelines.
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:
NCT00648648
Other Study ID Numbers:
- 1775-001
- 2007_611
- 2007-005304-40
- MK-1775-001
First Posted:
Apr 1, 2008
Last Update Posted:
Apr 5, 2019
Last Verified:
Jan 1, 2019