Multi-Dose Safety/Pharmacodynamic Study of SEL-212/SEL-037 in Subjects With Symptomatic Gout & Elevated Blood Uric Acid

• Sponsor: Selecta Biosciences, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02959918
• Collaborator: (none)
• Enrollment: 152
• Locations: 13
• Arms: 14
• Actual Duration (Months): 27
• Patients Per Site: 11.7
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

This is an open label multicenter study to evaluate the safety and tolerability of multiple doses (3 monthly IV infusions) of SEL-212 ( a combination of pegsiticase (SEL-037) and SVP-rapamycin (SEL-110)) followed by multiple doses (2 monthly IV infusions) of pegsiticase (SEL-037) alone for a total of 5 treatment cycles in subjects with symptomatic gout and hyperuricemia. Additional participants will be treated with multiple doses ( 5 monthly IV infusions) of pegsiticase (SEL-037) alone.

Participants will be monitored for safety endpoints through the 5th treatment cycle plus 30 days .Pharmacokinetic samples will be drawn at pre-determined time points in addition to weekly serum uric acid levels.

Condition or Disease	Intervention/Treatment	Phase
Gout Chronic; Hyperuricemia	Drug: SEL-212; Drug: SEL-037; Drug: SVP-rapamycin (SEL-110)	Phase 2

Detailed Description

This is an open label multicenter study to evaluate the safety and tolerability of multiple doses (3 monthly IV infusions) of SEL-212 ( a combination of pegsiticase ( SEL-037, also known as pegadricase) and SVP-rapamycin (SEL-110)) followed by multiple doses (2 monthly IV infusions) of pegsiticase (SEL-037) alone for a total of 5 treatment cycles in participants with symptomatic gout and hyperuricemia. Additional participants will be treated with multiple doses (5 monthly IV infusions) of pegsiticase (SEL-037) alone.

Uricase is an enzyme that converts uric acid to the readily soluble allantoin that is then excreted and SEL-110 is designed to prevent unwanted anti-drug-antibodies (ADAs) from forming. All participants will be monitored for safety and tolerability to drug throughout the study on a weekly schedule. Pharmacokinetic and pharmacodynamic parameters will at specific timepoints to monitor for continued efficacy. Pharmacodynamic parameters measured include uric acid levels and levels of ADAs.

The study duration per enrolled participant will be approximately 6 months including a 1 month screening period followed by 5 treatment cycles and an end of treatment visit which will occur 30 days after the last IV infusion .

Study Design

• Study Type: Interventional
• Actual Enrollment: 152 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open Label Phase II Multiple Dose Safety, Pharmacokinetic and Pharmacodynamics Study of SEL-212 Followed by Open Label Administration of SEL-037 in Subjects With Symptomatic Gout and Elevated Blood Uric Acid
• Actual Study Start Date: Oct 1, 2016
• Actual Primary Completion Date: Dec 1, 2018
• Actual Study Completion Date: Jan 1, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: SEL-037 Pegadricase LD (low dose) alone Pegadricase 0.2 mg/kg intravenous (IV) every 28 days for 5 treatments	Drug: SEL-037; SEL-037, biologic; Other Names: Pegadricase
Experimental: SEL-037 Pegadricase HD (high dose) alone Pegadricase 0.4 mg/kg intravenous (IV) every 28 days for 5 treatments	Drug: SEL-037; SEL-037, biologic; Other Names: Pegadricase
Experimental: SEL-212, Pegadricase LD & SEL-110 (1a) Pegadricase 0.2 mg/kg IV plus SEL-110 0.05 mg/kg IV every 28 days for 3 treatments, followed by pegadricase 0.2 mg/kg IV every 28 days for 2 treatments	Drug: SEL-212; SEL-212, biologic; Other Names: Pegadricase plus SVP-rapamycin ; Drug: SVP-rapamycin (SEL-110); SVP-rapamycin, biologic; Other Names: SEL-110
Experimental: SEL-212, Pegadricase HD & SEL-110 (1b) Pegadricase 0.4 mg/kg IV plus SEL-110 0.05 mg/kg IV every 28 days for 3 treatments, followed by pegadricase 0.4 mg/kg IV every 28 days for 2 treatments	Drug: SEL-212; SEL-212, biologic; Other Names: Pegadricase plus SVP-rapamycin ; Drug: SVP-rapamycin (SEL-110); SVP-rapamycin, biologic; Other Names: SEL-110
Experimental: SEL-212, Pegadricase LD & SEL-110 (2a) Pegadricase 0.2 mg/kg IV plus SEL-110 0.08 mg/kg IV every 28 days for 3 treatments, followed by pegadricase 0.2 mg/kg IV every 28 days for 2 treatments	Drug: SEL-212; SEL-212, biologic; Other Names: Pegadricase plus SVP-rapamycin ; Drug: SVP-rapamycin (SEL-110); SVP-rapamycin, biologic; Other Names: SEL-110
Experimental: SEL-212, Pegadricase HD & SEL-110 (2b) Pegadricase 0.4 mg/kg IV plus SEL-110 0.08 mg/kg IV every 28 days for 3 treatments, followed by pegadricase 0.4 mg/kg IV every 28 days for 2 treatments	Drug: SEL-212; SEL-212, biologic; Other Names: Pegadricase plus SVP-rapamycin ; Drug: SVP-rapamycin (SEL-110); SVP-rapamycin, biologic; Other Names: SEL-110
Experimental: SEL-212, Pegadricase HD & SEL-110 (3a) Pegadricase 0.2 mg/kg IV plus SEL-110 0.1 mg/kg IV every 28 days for 3 treatments, followed by pegadricase 0.2 mg/kg IV every 28 days for 2 treatments	Drug: SEL-212; SEL-212, biologic; Other Names: Pegadricase plus SVP-rapamycin ; Drug: SVP-rapamycin (SEL-110); SVP-rapamycin, biologic; Other Names: SEL-110
Experimental: SEL-212, Pegadricase HD & SEL-110 (3b) Pegadricase 0.4 mg/kg IV plus SEL-110 0.1 mg/kg IV every 28 days for 3 treatments, followed by pegadricase 0.4 mg/kg IV every 28 days for 2 treatments	Drug: SEL-212; SEL-212, biologic; Other Names: Pegadricase plus SVP-rapamycin ; Drug: SVP-rapamycin (SEL-110); SVP-rapamycin, biologic; Other Names: SEL-110
Experimental: SEL-212, Pegadricase HD & SEL-110 (4a) Pegadricase 0.4 mg/kg IV plus SEL-110 0.125 mg/kg IV every 28 days for 3 treatments, followed by pegadricase 0.4 mg/kg IV every 28 days for 2 treatments	Drug: SEL-212; SEL-212, biologic; Other Names: Pegadricase plus SVP-rapamycin ; Drug: SVP-rapamycin (SEL-110); SVP-rapamycin, biologic; Other Names: SEL-110
Experimental: SEL-212, Pegadricase HD & SEL-110 (4b) Pegadricase 0.2 mg/kg IV plus SEL-110 0.15 mg/kg IV every 28 days for 3 treatments, followed by pegadricase 0.2 mg/kg IV every 28 days for 2 treatments	Drug: SEL-212; SEL-212, biologic; Other Names: Pegadricase plus SVP-rapamycin ; Drug: SVP-rapamycin (SEL-110); SVP-rapamycin, biologic; Other Names: SEL-110
Experimental: SEL-212, Pegadricase HD & SEL-110 (5a) Pegadricase 0.4 mg/kg IV plus SEL-110 0.15 mg/kg IV every 28 days for 3 treatments, followed by pegadricase 0.4 mg/kg IV every 28 days for 2 treatments	Drug: SEL-212; SEL-212, biologic; Other Names: Pegadricase plus SVP-rapamycin ; Drug: SVP-rapamycin (SEL-110); SVP-rapamycin, biologic; Other Names: SEL-110
Experimental: SEL-212, Pegadricase HD & SEL-110 (5b) Pegadricase 0.2 mg/kg IV plus SEL-110 0.15 mg/kg IV every 28 days for 5 treatments	Drug: SEL-212; SEL-212, biologic; Other Names: Pegadricase plus SVP-rapamycin ; Drug: SVP-rapamycin (SEL-110); SVP-rapamycin, biologic; Other Names: SEL-110
Experimental: SEL-212, Pegadricase HD & SEL-110 (6a) Pegadricase 0.2 mg/kg IV plus SEL-110 0.10 mg/kg IV every 28 days for 1 treatment followed by pegadricase 0.2 mg/kg IV plus SEL-110 0.15 mg/kg IV every 28 days for 4 treatments	Drug: SEL-212; SEL-212, biologic; Other Names: Pegadricase plus SVP-rapamycin ; Drug: SVP-rapamycin (SEL-110); SVP-rapamycin, biologic; Other Names: SEL-110
Experimental: SEL-212, Pegadricase HD & SEL-110 (6b) Pegadricase 0.2 mg/kg IV plus SEL-110 0.1 mg/kg IV every 28 days for 5 treatments	Drug: SEL-212; SEL-212, biologic; Other Names: Pegadricase plus SVP-rapamycin ; Drug: SVP-rapamycin (SEL-110); SVP-rapamycin, biologic; Other Names: SEL-110

Outcome Measures

Primary Outcome Measures

1. Safety and Tolerability of Multiple Intravenous Infusions of SEL-037 or SEL-212 as Assessed by the Percentage of Participants Experiencing Serious Adverse Events and Those Adverse Events Reported by 5 Percentage or More in the Safety Analysis Set [Five monthly infusions]

   To determine the safety and tolerability of SEL-037 (pegadricase) after up to 5 monthly infusions, of SEL-212 for 3 monthly infusions followed by 2 monthly infusions of SEL-037 (pegadricase), or of SEL-212 for 5 monthly infusions as assessed by the percentage of participants in a treatment arm experiencing serious adverse events and percentage of participants experiencing those adverse events that were reported by 5 or more percentage of participants in any arm in the safety analysis set

Secondary Outcome Measures

1. Number of Participants With Reduced Serum Uric Acid After Multiple Monthly IV Infusions With or Without SEL-110 [3 and 5 months]

   Measurement of the number of participants with reduced serum uric acid after multiple monthly infusions with or without SEL-110 as determined by values of sUA < 6 mg/dL at the end of Treatment Period 3 and at the end of Treatment Period 5 in eligible subjects

Eligibility Criteria

Criteria

• Ages Eligible for Study: 21 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Adult (age 21-75 inclusive) men and women of non child bearing potential with established or symptomatic gout which is defined as having at least ONE of any of the 3 following factors:

2. ≥ 1 tophus

3. 1 gout flare within the last 6 months

4. Chronic gouty arthropathy

5. Screening serum uric acid of >6 mg/dL

6. On a gout flare prophylactic regimen for 7 days prior to first dose

7. Willing to provide written informed consent prior to first study procedure is performed.

8. Understands and is willing and able to comply with study requirements, including the schedule of follow-up visits.

Exclusion Criteria:

1. History of anaphylaxis or severe allergic reaction.

2. History of an allergy to pegylated products.

3. Women of child bearing potential, Defined as:

• <6 weeks after surgical bilateral salpingooperhectony with or without hysterectomy

• Pre or perimenopausal ( < less than 24 months of natural amenorrhea)

1. Initiation or change in dose of hormone-replacement therapy for menopausal women less than 1 month prior to the Screening Visit or during the Screening Phase would be exclusionary. If after being on a stable dose of hormone-replacement therapy for one month the patient may be considered for the study if she continues to meet all other inclusion and exclusion criteria

2. Uncontrolled diabetes with baseline HbA1c ≥8%;

3. Glucose-6-phosphate dehydrogenase deficiency;

4. Uncontrolled hypertension

5. Ongoing treatment for arrhythmia, including placement of an implantable defibrillator;

6. History of coronary artery disease, including myocardial infarction;

7. Congestive heart failure, New York Heart Association Class III or IV;

8. ECG with evidence of prior myocardial infarction, clinically significant arrhythmia, or other abnormalities that, in the opinion of the investigator, are consistent with significant underlying cardiac disease;

9. History of hematological or autoimmune disorders, is immunosuppressed or immunocompromised;

10. Prior exposure to any experimental or marketed uricase (e.g., rasburicase (Elitek, Fasturtec), pegloticase (Krystexxa®), pegsiticase (SEL-037)

11. History of malignancy within the last 5 years other than basal skin cancer;

12. Subjects who, in the opinion of the investigator, present with a condition that would compromise their safety or that would make study completion unlikely.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Anaheim Clinical Trials	Anaheim	California	United States	92801
2	Tri West Research Associates LLC	El Cajon	California	United States	92020
3	Irvine Center for Clinical Research Inc.	Irvine	California	United States	92614
4	Clinical Research of West Florida	Clearwater	Florida	United States	33765
5	Omega Research Consultants LLC	DeBary	Florida	United States	32713
6	Compass Research LLC	Orlando	Florida	United States	32806
7	East-West Medical Research Institute	Honolulu	Hawaii	United States	96814
8	Advanced Clinical Research	Boise	Idaho	United States	83642
9	L-MARC	Louisville	Kentucky	United States	40213
10	Triad Clinical Trials LLC	Greensboro	North Carolina	United States	27410
11	New Horizons Clinical Research	Cincinnati	Ohio	United States	45242
12	Altoona Center for Clinical Research	Duncansville	Pennsylvania	United States	16635
13	Advanced Clinical Research	West Jordan	Utah	United States	84088

Sponsors and Collaborators

• Selecta Biosciences, Inc.

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol - Mar 19, 2018
• Statistical Analysis Plan - Feb 12, 2019

More Information

Publications

None provided.

• Responsible Party: Selecta Biosciences, Inc.
• ClinicalTrials.gov Identifier: NCT02959918
• Other Study ID Numbers: SEL-212/201
• First Posted: Nov 9, 2016
• Last Update Posted: Feb 14, 2022
• Last Verified: Jan 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Additional relevant MeSH terms: Gout; Hyperuricemia; Sirolimus

Study Results

Participant Flow

Arm/Group Title	SEL-037 (Pegadricase) Low Dose	SEL-037 (Pegadricase) High Dose	SEL-212: SEL-110 (0.05 mg/kg) + SEL-037 Low Dose for 3 Doses Then SEL-037 Low Dose for 2 Doses	SEL-212: SEL-110 (0.05 mg/kg) + SEL-037 High Dose for 3 Doses Then SEL-037 High Dose for 2 Doses	SEL-212: SEL-110 (0.08 mg/kg) + SEL-037 Low Dose for 3 Doses Then SEL-037 Low Dose for 2 Doses	SEL-212: SEL-110 (0.08 mg/kg) + SEL-037 High Dose for 3 Doses Then SEL-037 High Dose for 2 Doses	SEL-212: SEL-110 (0.1 mg/kg) + SEL-037 Low Dose for 3 Doses Then SEL-037 Low Dose for 2 Doses	SEL-212: SEL-110 (0.1 mg/kg) + SEL-037 High Dose for 3 Doses Then SEL-037 High Dose for 2 Doses	SEL-212: SEL-110 (0.125 mg/kg) + SEL-037 High Dose for 3 Doses Then SEL-037 High Dose for 2 Doses	SEL-212: SEL-110 (0.15 mg/kg) + SEL-037 Low Dose for 3 Doses Then SEL-037 Low Dose for 2 Doses	SEL-212: SEL-110 (0.15 mg/kg) + SEL-037 High Dose for 3 Doses Then SEL-037 High Dose for 2 Doses	SEL-212: SEL-110 (0.15 mg/kg) + SEL-037 Low Dose for 5 Doses	SEL-212: SEL-110 0.15 mg/kg + SEL-037 Low 1 Dose Then SEL-110 0.1 mg/kg + SEL-037 Low for 4 Doses	SEL-212: SEL-110 (0.1 mg/kg) + SEL-037 Low Dose for 5 Doses
Arm/Group Description	Pegadricase 0.2 mg/kg IV every 28 days for up to 5 doses	Pegadricase 0.4mg/kg IV every 28 days for up to 5 doses	SEL-212 - Combination of SEL-110 (nanoparticle encapsulating rapamycin) 0.05 mg/kg + Pegadricase 0.2 mg/kg every 28 days for 3 doses followed by Pegadricase 0.2 mg/kg every 28 days for 2 doses	SEL-212 - Combination of SEL-110 (nanoparticle encapsulating rapamycin) 0.05 mg/kg + Pegadricase 0.4 mg/kg every 28 days for 3 doses followed by Pegadricase 0.4 mg/kg every 28 days for 2 doses	SEL-212 - Combination of SEL-110 (nanoparticle encapsulating rapamycin) 0.08 mg/kg + Pegadricase 0.2 mg/kg every 28 days for 3 doses followed by Pegadricase 0.2 mg/kg every 28 days for 2 doses	SEL-212 - Combination of SEL-110 (nanoparticle encapsulating rapamycin) 0.08 mg/kg + Pegadricase 0.4 mg/kg every 28 days for 3 doses followed by Pegadricase 0.4 mg/kg every 28 days for 2 doses	SEL-212 - Combination of SEL-110 (nanoparticle encapsulating rapamycin) 0.1 mg/kg + Pegadricase 0.2 mg/kg every 28 days for 3 doses followed by Pegadricase 0.2 mg/kg every 28 days for 2 doses	SEL-212 - Combination of SEL-110 (nanoparticle encapsulating rapamycin) 0.1 mg/kg + Pegadricase 0.4 mg/kg every 28 days for 3 doses followed by Pegadricase 0.4 mg/kg every 28 days for 2 doses	SEL-212 - Combination of SEL-110 (nanoparticle encapsulating rapamycin) 0.125 mg/kg + Pegadricase 0.4 mg/kg every 28 days for 3 doses followed by Pegadricase 0.4 mg/kg every 28 days for 2 doses	SEL-212 - Combination of SEL-110 (nanoparticle encapsulating rapamycin) 0.15 mg/kg + Pegadricase 0.2 mg/kg every 28 days for 3 doses followed by Pegadricase 0.2 mg/kg every 28 days for 2 doses	SEL-212 - Combination of SEL-110 (nanoparticle encapsulating rapamycin) 0.15 mg/kg + Pegadricase 0.4 mg/kg every 28 days for 3 doses followed by Pegadricase 0.4 mg/kg every 28 days for 2 doses	SEL-212 - Combination of SEL-110 (nanoparticle encapsulating rapamycin) 0.15 mg/kg + Pegadricase 0.2 mg/kg every 28 days for 5 doses	SEL-212 - Combination of SEL-110 (nanoparticle encapsulating rapamycin) 0.15 mg/kg + Pegadricase 0.2 mg/kg every 28 days for 1 dose then SEL-110 (0.1 mg/kg) + Pegadricase 0.2 mg/kg every 28 days for 4 doses	SEL-212 - Combination of SEL-110 (nanoparticle encapsulating rapamycin) 0.1 mg/kg + Pegadricase 0.2 mg/kg every 28 days for 5 doses
Period Title: Overall Study
STARTED	3	3	9	10	6	11	11	12	14	13	14	23	11	12
COMPLETED	0	0	1	1	1	5	6	6	7	7	8	11	4	6
NOT COMPLETED	3	3	8	9	5	6	5	6	7	6	6	12	7	6

Baseline Characteristics

Arm/Group Title	SEL-037 (Pegadricase) Low Dose	SEL-037 (Pegadricase) High Dose	SEL-212: SEL-110 (0.05 mg/kg) + SEL-037 Low Dose for 3 Doses Then SEL-037 Low Dose for 2 Doses	SEL-212: SEL-110 (0.05 mg/kg) + SEL-037 High Dose for 3 Doses Then SEL-037 High Dose for 2 Doses	SEL-212: SEL-110 (0.08 mg/kg) + SEL-037 Low Dose for 3 Doses Then SEL-037 Low Dose for 2 Doses	SEL-212: SEL-110 (0.08 mg/kg) + SEL-037 High Dose for 3 Doses Then SEL-037 High Dose for 2 Doses	SEL-212: SEL-110 (0.1 mg/kg) + SEL-037 Low Dose for 3 Doses Then SEL-037 Low Dose for 2 Doses	SEL-212: SEL-110 (0.1 mg/kg) + SEL-037 High Dose for 3 Doses Then SEL-037 High Dose for 2 Doses	SEL-212: SEL-110 (0.125 mg/kg) + SEL-037 High Dose for 3 Doses Then SEL-037 High Dose for 2 Doses	SEL-212: SEL-110 (0.15 mg/kg) + SEL-037 Low Dose for 3 Doses Then SEL-037 Low Dose for 2 Doses	SEL-212: SEL-110 (0.15 mg/kg) + SEL-037 High Dose for 3 Doses Then SEL-037 High Dose for 2 Doses	SEL-212: SEL-110 (0.15 mg/kg) + SEL-037 Low Dose for 5 Doses	SEL-212: SEL-110 (0.15 mg/kg) + SEL-037 Low for 1 Dose Then SEL-110 0.1 mg/kg + SEL-037 Low 4 Doses	SEL-212: SEL-110 (0.1 mg/kg) + SEL-037 Low Dose for 5 Doses	Total
Arm/Group Description	Pegardricase 0.2 mg/kg every 28 days for up to 5 doses	Pegardricase 0.4 mg/kg every 28 days for up to 5 doses	SEL-212 - Combination of SEL-110 (nanoparticle encapsulating rapamycin) 0.05 mg/kg + Pegadricase 0.2 mg/kg every 28 days for 3 doses followed by Pegadricase 0.2 mg/kg every 28 days for 2 doses	SEL-212 - Combination of SEL-110 (nanoparticle encapsulating rapamycin) 0.05 mg/kg + Pegadricase 0.4 mg/kg every 28 days for 3 doses followed by Pegadricase 0.4 mg/kg every 28 days for 2 doses	SEL-212 - Combination of SEL-110 (nanoparticle encapsulating rapamycin) 0.08 mg/kg + Pegadricase 0.2 mg/kg every 28 days for 3 doses followed by Pegadricase 0.2 mg/kg every 28 days for 2 doses	SEL-212 - Combination of SEL-110 (nanoparticle encapsulating rapamycin) 0.08 mg/kg + Pegadricase 0.4 mg/kg every 28 days for 3 doses followed by Pegadricase 0.4 mg/kg every 28 days for 2 doses	SEL-212 - Combination of SEL-110 (nanoparticle encapsulating rapamycin) 0.1 mg/kg + Pegadricase 0.2 mg/kg every 28 days for 3 doses followed by Pegadricase 0.2 mg/kg every 28 days for 2 doses	SEL-212 - Combination of SEL-110 (nanoparticle encapsulating rapamycin) 0.1 mg/kg + Pegadricase 0.4 mg/kg every 28 days for 3 doses followed by Pegadricase 0.4 mg/kg every 28 days for 2 doses	SEL-212 - Combination of SEL-110 (nanoparticle encapsulating rapamycin) 0.125 mg/kg + Pegadricase 0.4 mg/kg every 28 days for 3 doses followed by Pegadricase 0.4 mg/kg every 28 days for 2 doses	SEL-212 - Combination of SEL-110 (nanoparticle encapsulating rapamycin) 0.15 mg/kg + Pegadricase 0.2 mg/kg every 28 days for 3 doses followed by Pegadricase 0.2 mg/kg every 28 days for 2 doses	SEL-212 - Combination of SEL-110 (nanoparticle encapsulating rapamycin) 0.15 mg/kg + Pegadricase 0.4 mg/kg every 28 days for 3 doses followed by Pegadricase 0.4 mg/kg every 28 days for 2 doses	SEL-212 - Combination of SEL-110 (nanoparticle encapsulating rapamycin) 0.15 mg/kg + Pegadricase 0.2 mg/kg every 28 days for 5 doses	SEL-212: Combination of SEL-110 (nanoparticle encapsulating rapamycin) 0.15 mg/kg + Pegadricase 0.2 mg/kg every 28 days for 1 Dose Then SEL-110 0.1 mg/kg + Pegadricase 0.2 mg/kg every 28 days for 4 Doses	SEL-212 - Combination of SEL-110 (nanoparticle encapsulating rapamycin) 0.1 mg/kg + Pegadricase 0.2 mg/kg every 28 days for 5 doses	Total of all reporting groups
Overall Participants	3	3	9	10	6	11	11	12	14	13	14	23	11	12	152
Age (Count of Participants)
<=18 years	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%
Between 18 and 65 years	3 100%	3 100%	7 77.8%	9 90%	4 66.7%	6 54.5%	10 90.9%	10 83.3%	8 57.1%	12 92.3%	12 85.7%	21 91.3%	11 100%	10 83.3%	126 82.9%
>=65 years	0 0%	0 0%	2 22.2%	1 10%	2 33.3%	5 45.5%	1 9.1%	2 16.7%	6 42.9%	1 7.7%	2 14.3%	2 8.7%	0 0%	2 16.7%	26 17.1%
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%	1 10%	0 0%	3 27.3%	1 9.1%	2 16.7%	2 14.3%	1 7.7%	3 21.4%	1 4.3%	0 0%	0 0%	14 9.2%
Male	3 100%	3 100%	9 100%	9 90%	6 100%	8 72.7%	10 90.9%	10 83.3%	12 85.7%	12 92.3%	11 78.6%	22 95.7%	11 100%	12 100%	138 90.8%
Race/Ethnicity, Customized (Count of Participants)
American Indian or Alaska Native	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%
Asian	0 0%	0 0%	0 0%	1 10%	0 0%	0 0%	0 0%	0 0%	2 14.3%	0 0%	0 0%	1 4.3%	0 0%	0 0%	4 2.6%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	2 20%	0 0%	0 0%	0 0%	0 0%	0 0%	1 7.7%	0 0%	1 4.3%	0 0%	0 0%	4 2.6%
Black or African American	1 33.3%	2 66.7%	2 22.2%	2 20%	2 33.3%	2 18.2%	3 27.3%	4 33.3%	2 14.3%	6 46.2%	4 28.6%	7 30.4%	1 9.1%	2 16.7%	40 26.3%
White	2 66.7%	0 0%	7 77.8%	5 50%	4 66.7%	9 81.8%	8 72.7%	8 66.7%	10 71.4%	6 46.2%	10 71.4%	14 60.9%	10 90.9%	10 83.3%	103 67.8%
Unknown or Not Reported	0 0%	1 33.3%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	1 0.7%

Outcome Measures

1. Primary Outcome

Title	Safety and Tolerability of Multiple Intravenous Infusions of SEL-037 or SEL-212 as Assessed by the Percentage of Participants Experiencing Serious Adverse Events and Those Adverse Events Reported by 5 Percentage or More in the Safety Analysis Set
Description	To determine the safety and tolerability of SEL-037 (pegadricase) after up to 5 monthly infusions, of SEL-212 for 3 monthly infusions followed by 2 monthly infusions of SEL-037 (pegadricase), or of SEL-212 for 5 monthly infusions as assessed by the percentage of participants in a treatment arm experiencing serious adverse events and percentage of participants experiencing those adverse events that were reported by 5 or more percentage of participants in any arm in the safety analysis set
Time Frame	Five monthly infusions

Outcome Measure Data

Analysis Population Description

Safety analysis set, dosed subjects

Arm/Group Title	SEL-037 (Pegadricase) Low Dose	SEL-037 (Pegadricase) High Dose	SEL-212: SEL-110 (0.05 mg/kg) + SEL-037 Low Dose for 3 Doses Then SEL-037 Low Dose for 2 Doses	SEL-212: SEL-110(0.05 mg/kg) + SEL-037 High Dose for 3 Doses Then SEL-037(0.4 mg/kg) for 2 Doses	SEL-212: SEL-110 (0.08 mg/kg) + SEL-037 Low Dose for 3 Doses Then SEL-037 Low Dose for 2 Doses	SEL-212: SEL-110 (0.08 mg/kg) + SEL-037 High Dose for 3 Doses Then SEL-037 High Dose for 2 Doses	SEL-212: SEL-110 (0.1 mg/kg) + SEL-037 Low Dose for 3 Doses Then SEL-037 Low Dose for 2 Doses	SEL-212: SEL-110 (0.1 mg/kg) + SEL-037 High Dose for 3 Doses Then SEL-037 High Dose for 2 Doses	SEL-212: SEL-110 (0.125 mg/kg) + SEL-037 High Dose for 3 Doses Then SEL-037 High Dose for 2 Doses	SEL-212: SEL-110 (0.15 mg/kg) + SEL-037 Low Dose for 3 Doses Then SEL-037 Low Dose for 2 Doses	SEL-212: SEL-110 (0.15 mg/kg) + SEL-037 High Dose for 3 Doses Then SEL-037 High Dose for 2 Doses	SEL-212: SEL-110 (0.15 mg/kg) + SEL-037 Low Dose for 5 Doses	SEL-212: SEL-110 0.15 mg/kg + SEL-037 Low Dose x 1 Then SEL-110 0.1 mg/kg + SEL-037 Low x 4 Doses	SEL-212: SEL-110 (0.1 mg/kg) + SEL-037 Low Dose for 5 Doses
Arm/Group Description	Pegadricase 0.2 mg/kg IV every 28 days for up to 5 doses	Pegadricase 0.4mg/kg IV every 28 days for up to 5 doses	SEL-212 - Combination of SEL-110 (nanoparticle encapsulating rapamycin) 0.05 mg/kg + Pegadricase 0.2 mg/kg every 28 days for 3 doses followed by Pegadricase 0.2 mg/kg every 28 days for 2 doses	SEL-212 - Combination of SEL-110 (nanoparticle encapsulating rapamycin) 0.05 mg/kg + Pegadricase 0.4 mg/kg every 28 days for 3 doses followed by Pegadricase 0.4 mg/kg every 28 days for 2 doses	SEL-212 - Combination of SEL-110 (nanoparticle encapsulating rapamycin) 0.08 mg/kg + SEL-037 (pegadricase) 0.2 mg/kg every 28 days for 3 doses followed by SEL-037 0.2 mg/kg every 28 days for 2 doses	SEL-212 - Combination of SEL-110 (nanoparticle encapsulating rapamycin) 0.08 mg/kg + Pegadricase 0.4 mg/kg every 28 days for 3 doses followed by Pegadricase 0.4 mg/kg every 28 days for 2 doses	SEL-212 - Combination of SEL-110 (nanoparticle encapsulating rapamycin) 0.1 mg/kg + Pegadricase 0.2 mg/kg every 28 days for 3 doses followed by Pegadricase 0.2 mg/kg every 28 days for 2 doses	SEL-212 - Combination of SEL-110 (nanoparticle encapsulating rapamycin) 0.1 mg/kg + Pegadricase 0.4 mg/kg every 28 days for 3 doses followed by Pegadricase 0.4 mg/kg every 28 days for 2 doses	SEL-212 - Combination of SEL-110 (nanoparticle encapsulating rapamycin) 0.125 mg/kg + Pegadricase 0.4 mg/kg every 28 days for 3 doses followed by Pegadricase 0.4 mg/kg every 28 days for 2 doses	SEL-212 - Combination of SEL-110 (nanoparticle encapsulating rapamycin) 0.15 mg/kg + Pegadricase 0.2 mg/kg every 28 days for 3 doses followed by Pegadricase 0.2 mg/kg every 28 days for 2 doses	SEL-212 - Combination of SEL-110 (nanoparticle encapsulating rapamycin) 0.15 mg/kg + Pegadricase 0.4 mg/kg every 28 days for 3 doses followed by Pegadricase 0.4 mg/kg every 28 days for 2 doses	SEL-212 - Combination of SEL-110 (nanoparticle encapsulating rapamycin) 0.15 mg/kg + Pegadricase 0.2 mg/kg every 28 days for 5 doses	SEL-212: Combination of SEL-110 (nanoparticle encapsulating rapamycin) 0.15 mg/kg + Pegadricase 0.2 mg/kg x 1 Then SEL-110 0.1 mg/kg + Pegadricase 0.2 mg/kg x 4 Doses	SEL-212: Combination of SEL-110 (nanoparticle encapsulating rapamycin) 0.1 mg/kg + Pegadricase 0.2 mg/kg every 28 days for 5 doses
Measure Participants	3	3	9	10	6	11	11	12	14	13	14	23	11	12
Count of Participants [Participants]	3 100%	3 100%	9 100%	10 100%	6 100%	11 100%	11 100%	12 100%	14 100%	13 100%	14 100%	23 100%	11 100%	12 100%

2. Secondary Outcome

Title	Number of Participants With Reduced Serum Uric Acid After Multiple Monthly IV Infusions With or Without SEL-110
Description	Measurement of the number of participants with reduced serum uric acid after multiple monthly infusions with or without SEL-110 as determined by values of sUA < 6 mg/dL at the end of Treatment Period 3 and at the end of Treatment Period 5 in eligible subjects
Time Frame	3 and 5 months

Outcome Measure Data

Analysis Population Description

Eligible subjects are those who received the entire first dose, did not discontinue due to withdrawal of consent (during TP 1-4), a protocol deviation (during TP1-2) or a non-study drug-related SAE (during TP1-2). The outcome data is presented with arms combined by regimen (i.e. SEL-037 alone; SEL-212 for 3 doses & SEL-037 for 2 doses; or SEL-212 for 5 doses) rather than by dosing arm as the outcome is most effected by the SEL-212 combination which results in suppression of anti-drug antibodies.

Arm/Group Title	SEL-037 (Pegadricase)	SEL-212 for 3 Doses Followed by SEL-037 for 2 Doses	SEL-212 for 5 Doses
Arm/Group Description	SEL-037 every 28 days for up to 5 doses	SEL-212 - Combination of SEL-110 (nanoparticle encapsulating rapamycin) + SEL-037 (pegadricase) every 28 days for 3 doses followed by SEL-037 every 28 days for 2 doses	SEL-212 - Combination of SEL-110 (nanoparticle encapsulating rapamycin) + SEL-037 (pegadricase) every 28 days for 5 doses
Measure Participants	3	73	32
Treatment Period 3	0 0%	51 1700%	23 255.6%
Treatment Period 5	NA NaN	27 900%	21 233.3%

3. Secondary Outcome

Title	Number of Participants With Reduced Serum Uric Acid After Multiple Monthly IV Infusions With or Without SEL-110
Description	Measurement of the number of participants with reduced serum uric acid after multiple monthly infusions with or without SEL-110 as determined by values of sUA < 6 mg/dL at the end of Treatment Period 3 and at the end of Treatment Period 5 in eligible subjects
Time Frame	3 and 5 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	SEL-037 (Pegadricase) Low Dose	SEL-037 (Pegadricase) High Dose	SEL-212: SEL-110 (0.05 mg/kg) + SEL-037 Low Dose for 3 Doses Then SEL-037 Low Dose for 2 Doses	SEL-212: SEL-110(0.05 mg/kg) + SEL-037 High Dose for 3 Doses Then SEL-037(0.4 mg/kg) for 2 Doses	SEL-212: SEL-110 (0.08 mg/kg) + SEL-037 Low Dose for 3 Doses Then SEL-037 Low Dose for 2 Doses	SEL-212: SEL-110 (0.08 mg/kg) + SEL-037 High Dose for 3 Doses Then SEL-037 High Dose for 2 Doses	SEL-212: SEL-110 (0.1 mg/kg) + SEL-037 Low Dose for 3 Doses Then SEL-037 Low Dose for 2 Doses	SEL-212: SEL-110 (0.1 mg/kg) + SEL-037 High Dose for 3 Doses Then SEL-037 High Dose for 2 Doses	SEL-212: SEL-110 (0.125 mg/kg) + SEL-037 High Dose for 3 Doses Then SEL-037 High Dose for 2 Doses	SEL-212: SEL-110 (0.15 mg/kg) + SEL-037 Low Dose for 3 Doses Then SEL-037 Low Dose for 2 Doses	SEL-212: SEL-110 (0.15 mg/kg) + SEL-037 High Dose for 3 Doses Then SEL-037 High Dose for 2 Doses	SEL-212: SEL-110 (0.15 mg/kg) + SEL-037 Low Dose for 5 Doses	SEL-212: SEL-110 0.15 mg/kg + SEL-037 Low Dose x 1 Then SEL-110 0.1 mg/kg + SEL-037 Low x 4 Doses	SEL-212: SEL-110 (0.1 mg/kg) + SEL-037 Low Dose for 5 Doses
Arm/Group Description	Pegadricase 0.2 mg/kg IV every 28 days for up to 5 doses	Pegadricase 0.4mg/kg IV every 28 days for up to 5 doses	SEL-212 - Combination of SEL-110 (nanoparticle encapsulating rapamycin) 0.05 mg/kg + Pegadricase 0.2 mg/kg every 28 days for 3 doses followed by Pegadricase 0.2 mg/kg every 28 days for 2 doses	SEL-212 - Combination of SEL-110 (nanoparticle encapsulating rapamycin) 0.05 mg/kg + Pegadricase 0.4 mg/kg every 28 days for 3 doses followed by Pegadricase 0.4 mg/kg every 28 days for 2 doses	SEL-212 - Combination of SEL-110 (nanoparticle encapsulating rapamycin) 0.08 mg/kg + SEL-037 (pegadricase) 0.2 mg/kg every 28 days for 3 doses followed by SEL-037 0.2 mg/kg every 28 days for 2 doses	SEL-212 - Combination of SEL-110 (nanoparticle encapsulating rapamycin) 0.08 mg/kg + Pegadricase 0.4 mg/kg every 28 days for 3 doses followed by Pegadricase 0.4 mg/kg every 28 days for 2 doses	SEL-212 - Combination of SEL-110 (nanoparticle encapsulating rapamycin) 0.1 mg/kg + Pegadricase 0.2 mg/kg every 28 days for 3 doses followed by Pegadricase 0.2 mg/kg every 28 days for 2 doses	SEL-212 - Combination of SEL-110 (nanoparticle encapsulating rapamycin) 0.1 mg/kg + Pegadricase 0.4 mg/kg every 28 days for 3 doses followed by Pegadricase 0.4 mg/kg every 28 days for 2 doses	SEL-212 - Combination of SEL-110 (nanoparticle encapsulating rapamycin) 0.125 mg/kg + Pegadricase 0.4 mg/kg every 28 days for 3 doses followed by Pegadricase 0.4 mg/kg every 28 days for 2 doses	SEL-212 - Combination of SEL-110 (nanoparticle encapsulating rapamycin) 0.15 mg/kg + Pegadricase 0.2 mg/kg every 28 days for 3 doses followed by Pegadricase 0.2 mg/kg every 28 days for 2 doses	SEL-212 - Combination of SEL-110 (nanoparticle encapsulating rapamycin) 0.15 mg/kg + Pegadricase 0.4 mg/kg every 28 days for 3 doses followed by Pegadricase 0.4 mg/kg every 28 days for 2 doses	SEL-212 - Combination of SEL-110 (nanoparticle encapsulating rapamycin) 0.15 mg/kg + Pegadricase 0.2 mg/kg every 28 days for 5 doses	SEL-212: Combination of SEL-110 (nanoparticle encapsulating rapamycin) 0.15 mg/kg + Pegadricase 0.2 mg/kg x 1 Then SEL-110 0.1 mg/kg + Pegadricase 0.2 mg/kg x 4 Doses	SEL-212: Combination of SEL-110 (nanoparticle encapsulating rapamycin) 0.1 mg/kg + Pegadricase 0.2 mg/kg every 28 days for 5 doses
Measure Participants	2	1	6	5	6	8	10	10	8	9	11	18	6	8
Treatment Period 3	0 0%	0 0%	2 22.2%	1 10%	4 66.7%	6 54.5%	7 63.6%	7 58.3%	7 50%	8 61.5%	9 64.3%	12 52.2%	5 45.5%	6 50%
Treatment Period 5	NA NaN	NA NaN	1 11.1%	1 10%	0 0%	3 27.3%	3 27.3%	4 33.3%	5 35.7%	4 30.8%	6 42.9%	11 47.8%	4 36.4%	6 50%

Adverse Events

Time Frame	5 months
Arm/Group Title	SEL-037 (Pegadricase) Low Dose		SEL-037 (Pegadricase) High Dose		SEL-212: SEL-110 (0.05 mg/kg) + SEL-037 Low Dose for 3 Doses Then SEL-037 Low Dose for 2 Doses		SEL-212: SEL-110 (0.05 mg/kg) + SEL-037 High Dose for 3 Doses Then SEL-037 High Dose for 2 Doses		SEL-212: SEL-110 (0.08 mg/kg) + SEL-037 Low Dose for 3 Doses Then SEL-037 Low Dose for 2 Doses		SEL-212: SEL-110 (0.08 mg/kg) + SEL-037 High Dose for 3 Doses Then SEL-037 High Dose for 2 Doses		SEL-212: SEL-110 (0.1 mg/kg) + SEL-037 Low Dose for 3 Doses Then SEL-037 Low Dose for 2 Doses		SEL-212: SEL-110 (0.1 mg/kg) + SEL-037 High Dose for 3 Doses Then SEL-037 High Dose for 2 Doses		SEL-212: SEL-110 (0.125 mg/kg) + SEL-037 High Dose for 3 Doses Then SEL-037 High Dose for 2 Doses		SEL-212: SEL-110 (0.15 mg/kg) + SEL-037 Low Dose for 3 Doses Then SEL-037 Low Dose for 2 Doses		SEL-212: SEL-110 (0.15 mg/kg) + SEL-037 High Dose for 3 Doses Then SEL-037 High Dose for 2 Doses		SEL-212: SEL-110 (0.15 mg/kg) + SEL-037 Low Dose for 5 Doses		SEL-212: SEL-110 0.15 mg/kg + SEL-037 Low x 1 Then SEL-110 0.1 mg/kg + SEL-037 Low Dose x 4 Doses		SEL-212: SEL-110 (0.1 mg/kg) + SEL-037 Low Dose for 5 Doses
Arm/Group Description	Pegadricase 0.2 mg/kg IV every 28 days for up to 5 doses		Pegadricase 0.4 mg/kg IV every 28 days for up to 5 doses		SEL-212 - Combination of SEL-110 (nanoparticle encapsulating rapamycin) 0.05 mg/kg + Pegadricase 0.2 mg/kg IV every 28 days for 3 doses followed by Pegadricase 0.2 mg/kg IV every 28 days for 2 doses		SEL-212 - Combination of SEL-110 (nanoparticle encapsulating rapamycin) 0.05 mg/kg + Pegadricase 0.4 mg/kg IV every 28 days for 3 doses followed by Pegadricase 0.4 mg/kg IV every 28 days for 2 doses		SEL-212 - Combination of SEL-110 (nanoparticle encapsulating rapamycin) 0.08 mg/kg + Pegadricase 0.2 mg/kg IV every 28 days for 3 doses followed by Pegadricase 0.2 mg/kg IV every 28 days for 2 doses		SEL-212 - Combination of SEL-110 (nanoparticle encapsulating rapamycin) 0.08 mg/kg + Pegadricase 0.4 mg/kg IV every 28 days for 3 doses followed by Pegadricase 0.4 mg/kg IV every 28 days for 2 doses		SEL-212 - Combination of SEL-110 (nanoparticle encapsulating rapamycin) 0.1 mg/kg + Pegadricase 0.2 mg/kg IV every 28 days for 3 doses followed by Pegadricase 0.2 mg/kg IV every 28 days for 2 doses		SEL-212 - Combination of SEL-110 (nanoparticle encapsulating rapamycin) 0.1 mg/kg + Pegadricase 0.4 mg/kg IV every 28 days for 3 doses followed by Pegadricase 0.4 mg/kg IV every 28 days for 2 doses		SEL-212 - Combination of SEL-110 (nanoparticle encapsulating rapamycin) 0.125 mg/kg + Pegadricase 0.4 mg/kg IV every 28 days for 3 doses followed by Pegadricase 0.4 mg/kg IV every 28 days for 2 doses		SEL-212 - Combination of SEL-110 (nanoparticle encapsulating rapamycin) 0.15 mg/kg + Pegadricase 0.2 mg/kg IV every 28 days for 3 doses followed by Pegadricase 0.2 mg/kg IV every 28 days for 2 doses		SEL-212 - Combination of SEL-110 (nanoparticle encapsulating rapamycin) 0.15 mg/kg + Pegadricase 0.4 mg/kg IV every 28 days for 3 doses followed by Pegadricase 0.4 mg/kg IV every 28 days for 2 doses		SEL-212 - Combination of SEL-110 (nanoparticle encapsulating rapamycin) 0.15 mg/kg + Pegadricase 0.2 mg/kg IV every 28 days for 5 doses		SEL-212 - Combination of SEL-110 (nanoparticle encapsulating rapamycin) 0.15 mg/kg + Pegadricase 0.2 mg/kg x 1 dose then SEL-110 0.1 mg/kg + Pegadricase 0.2 mg/kg x 4 doses IV every 28 days		SEL-212 - Combination of SEL-110 (nanoparticle encapsulating rapamycin) 0.1 mg/kg + Pegadricase 0.2 mg/kg IV every 28 days for 5 doses
All Cause Mortality
	SEL-037 (Pegadricase) Low Dose		SEL-037 (Pegadricase) High Dose		SEL-212: SEL-110 (0.05 mg/kg) + SEL-037 Low Dose for 3 Doses Then SEL-037 Low Dose for 2 Doses		SEL-212: SEL-110 (0.05 mg/kg) + SEL-037 High Dose for 3 Doses Then SEL-037 High Dose for 2 Doses		SEL-212: SEL-110 (0.08 mg/kg) + SEL-037 Low Dose for 3 Doses Then SEL-037 Low Dose for 2 Doses		SEL-212: SEL-110 (0.08 mg/kg) + SEL-037 High Dose for 3 Doses Then SEL-037 High Dose for 2 Doses		SEL-212: SEL-110 (0.1 mg/kg) + SEL-037 Low Dose for 3 Doses Then SEL-037 Low Dose for 2 Doses		SEL-212: SEL-110 (0.1 mg/kg) + SEL-037 High Dose for 3 Doses Then SEL-037 High Dose for 2 Doses		SEL-212: SEL-110 (0.125 mg/kg) + SEL-037 High Dose for 3 Doses Then SEL-037 High Dose for 2 Doses		SEL-212: SEL-110 (0.15 mg/kg) + SEL-037 Low Dose for 3 Doses Then SEL-037 Low Dose for 2 Doses		SEL-212: SEL-110 (0.15 mg/kg) + SEL-037 High Dose for 3 Doses Then SEL-037 High Dose for 2 Doses		SEL-212: SEL-110 (0.15 mg/kg) + SEL-037 Low Dose for 5 Doses		SEL-212: SEL-110 0.15 mg/kg + SEL-037 Low x 1 Then SEL-110 0.1 mg/kg + SEL-037 Low Dose x 4 Doses		SEL-212: SEL-110 (0.1 mg/kg) + SEL-037 Low Dose for 5 Doses
	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%)		0/9 (0%)		0/10 (0%)		0/6 (0%)		0/11 (0%)		0/11 (0%)		0/12 (0%)		0/14 (0%)		0/13 (0%)		0/14 (0%)		0/23 (0%)		0/11 (0%)		0/12 (0%)
Serious Adverse Events
	SEL-037 (Pegadricase) Low Dose		SEL-037 (Pegadricase) High Dose		SEL-212: SEL-110 (0.05 mg/kg) + SEL-037 Low Dose for 3 Doses Then SEL-037 Low Dose for 2 Doses		SEL-212: SEL-110 (0.05 mg/kg) + SEL-037 High Dose for 3 Doses Then SEL-037 High Dose for 2 Doses		SEL-212: SEL-110 (0.08 mg/kg) + SEL-037 Low Dose for 3 Doses Then SEL-037 Low Dose for 2 Doses		SEL-212: SEL-110 (0.08 mg/kg) + SEL-037 High Dose for 3 Doses Then SEL-037 High Dose for 2 Doses		SEL-212: SEL-110 (0.1 mg/kg) + SEL-037 Low Dose for 3 Doses Then SEL-037 Low Dose for 2 Doses		SEL-212: SEL-110 (0.1 mg/kg) + SEL-037 High Dose for 3 Doses Then SEL-037 High Dose for 2 Doses		SEL-212: SEL-110 (0.125 mg/kg) + SEL-037 High Dose for 3 Doses Then SEL-037 High Dose for 2 Doses		SEL-212: SEL-110 (0.15 mg/kg) + SEL-037 Low Dose for 3 Doses Then SEL-037 Low Dose for 2 Doses		SEL-212: SEL-110 (0.15 mg/kg) + SEL-037 High Dose for 3 Doses Then SEL-037 High Dose for 2 Doses		SEL-212: SEL-110 (0.15 mg/kg) + SEL-037 Low Dose for 5 Doses		SEL-212: SEL-110 0.15 mg/kg + SEL-037 Low x 1 Then SEL-110 0.1 mg/kg + SEL-037 Low Dose x 4 Doses		SEL-212: SEL-110 (0.1 mg/kg) + SEL-037 Low Dose for 5 Doses
	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	1/3 (33.3%)		1/3 (33.3%)		2/9 (22.2%)		0/10 (0%)		0/6 (0%)		1/11 (9.1%)		2/11 (18.2%)		4/12 (33.3%)		2/14 (14.3%)		0/13 (0%)		1/14 (7.1%)		3/23 (13%)		1/11 (9.1%)		2/12 (16.7%)
Cardiac disorders
Acute Myocardial Infarction	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	0/6 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	1/14 (7.1%)	1	0/13 (0%)	0	0/14 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0
Atrioventricular block	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	0/6 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	1/12 (8.3%)	1	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0
Arrhythmia	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	0/6 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	1/23 (4.3%)	2	0/11 (0%)	0	0/12 (0%)	0
Cardiac failure	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	0/6 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	1/12 (8.3%)	2
Gastrointestinal disorders
Acute Pancreatitis	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	0/6 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	1/12 (8.3%)	1	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0
Dysphagia	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	0/6 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/23 (0%)	0	1/11 (9.1%)	2	0/12 (0%)	0
General disorders
Peripheral oedema	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	0/6 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	1/12 (8.3%)	1	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0
Hepatobiliary disorders
Acute cholecystitis	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	0/6 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	1/12 (8.3%)	1	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0
Cholecystitis	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	0/6 (0%)	0	0/11 (0%)	0	1/11 (9.1%)	1	0/12 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0
Immune system disorders
Anaphylactic reaction	1/3 (33.3%)	1	0/3 (0%)	0	1/9 (11.1%)	1	0/10 (0%)	0	0/6 (0%)	0	0/11 (0%)	0	1/11 (9.1%)	1	1/12 (8.3%)	1	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	1/23 (4.3%)	1	0/11 (0%)	0	0/12 (0%)	0
Anaphylactic shock	0/3 (0%)	0	1/3 (33.3%)	1	0/9 (0%)	0	0/10 (0%)	0	0/6 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0
Infections and infestations
Cellulitis	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	0/6 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	1/12 (8.3%)	1
Pneumonia	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	0/6 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	1/14 (7.1%)	1	0/13 (0%)	0	0/14 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0
Pyelonephritis	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	0/6 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	1/14 (7.1%)	1	1/23 (4.3%)	1	0/11 (0%)	0	0/12 (0%)	0
Soft tissue infection	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	0/6 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	1/12 (8.3%)	1
Injury, poisoning and procedural complications
Infusion related reaction	0/3 (0%)	0	0/3 (0%)	0	1/9 (11.1%)	1	0/10 (0%)	0	0/6 (0%)	0	1/11 (9.1%)	1	0/11 (0%)	0	0/12 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	1/12 (8.3%)	1
Metabolism and nutrition disorders
Dehydration	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	0/6 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/23 (0%)	0	1/11 (9.1%)	2	0/12 (0%)	0
Gout flare	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	0/6 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	1/14 (7.1%)	1	0/13 (0%)	0	0/14 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0
Renal and urinary disorders
Acute kidney injury	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	0/6 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	1/12 (8.3%)	1	0/14 (0%)	0	0/13 (0%)	0	1/14 (7.1%)	1	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0
Micturition disorder	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	0/6 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	1/12 (8.3%)	1	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0
Renal tubular necrosis	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	0/6 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	1/23 (4.3%)	1	0/11 (0%)	0	0/12 (0%)	0
Other (Not Including Serious) Adverse Events
	SEL-037 (Pegadricase) Low Dose		SEL-037 (Pegadricase) High Dose		SEL-212: SEL-110 (0.05 mg/kg) + SEL-037 Low Dose for 3 Doses Then SEL-037 Low Dose for 2 Doses		SEL-212: SEL-110 (0.05 mg/kg) + SEL-037 High Dose for 3 Doses Then SEL-037 High Dose for 2 Doses		SEL-212: SEL-110 (0.08 mg/kg) + SEL-037 Low Dose for 3 Doses Then SEL-037 Low Dose for 2 Doses		SEL-212: SEL-110 (0.08 mg/kg) + SEL-037 High Dose for 3 Doses Then SEL-037 High Dose for 2 Doses		SEL-212: SEL-110 (0.1 mg/kg) + SEL-037 Low Dose for 3 Doses Then SEL-037 Low Dose for 2 Doses		SEL-212: SEL-110 (0.1 mg/kg) + SEL-037 High Dose for 3 Doses Then SEL-037 High Dose for 2 Doses		SEL-212: SEL-110 (0.125 mg/kg) + SEL-037 High Dose for 3 Doses Then SEL-037 High Dose for 2 Doses		SEL-212: SEL-110 (0.15 mg/kg) + SEL-037 Low Dose for 3 Doses Then SEL-037 Low Dose for 2 Doses		SEL-212: SEL-110 (0.15 mg/kg) + SEL-037 High Dose for 3 Doses Then SEL-037 High Dose for 2 Doses		SEL-212: SEL-110 (0.15 mg/kg) + SEL-037 Low Dose for 5 Doses		SEL-212: SEL-110 0.15 mg/kg + SEL-037 Low x 1 Then SEL-110 0.1 mg/kg + SEL-037 Low Dose x 4 Doses		SEL-212: SEL-110 (0.1 mg/kg) + SEL-037 Low Dose for 5 Doses
	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	3/3 (100%)		3/3 (100%)		8/9 (88.9%)		8/10 (80%)		6/6 (100%)		10/11 (90.9%)		10/11 (90.9%)		12/12 (100%)		14/14 (100%)		12/13 (92.3%)		14/14 (100%)		21/23 (91.3%)		9/11 (81.8%)		12/12 (100%)
Blood and lymphatic system disorders
Anaemia	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	2/6 (33.3%)	2	3/11 (27.3%)	4	1/11 (9.1%)	2	4/12 (33.3%)	4	3/14 (21.4%)	4	1/13 (7.7%)	2	3/14 (21.4%)	3	1/23 (4.3%)	1	1/11 (9.1%)	1	2/12 (16.7%)	2
Leukopenia	0/3 (0%)	0	0/3 (0%)	0	1/9 (11.1%)	1	0/10 (0%)	0	1/6 (16.7%)	2	1/11 (9.1%)	1	1/11 (9.1%)	2	3/12 (25%)	3	1/14 (7.1%)	1	1/13 (7.7%)	3	2/14 (14.3%)	2	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0
Lymphopenia	0/3 (0%)	0	0/3 (0%)	0	1/9 (11.1%)	1	0/10 (0%)	0	1/6 (16.7%)	1	0/11 (0%)	0	0/11 (0%)	0	1/12 (8.3%)	1	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0
Hyperfibrinogenaemia	0/3 (0%)	0	0/3 (0%)	0	1/9 (11.1%)	1	0/10 (0%)	0	0/6 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0
Thrombocytosis	0/3 (0%)	0	0/3 (0%)	0	1/9 (11.1%)	1	0/10 (0%)	0	0/6 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0
Leukocytosis	0/3 (0%)	0	0/3 (0%)	0	1/9 (11.1%)	1	0/10 (0%)	0	0/6 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0
Lymphadenopathy	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	1/10 (10%)	1	0/6 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0
Thrombocytopenia	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	1/6 (16.7%)	1	1/11 (9.1%)	1	0/11 (0%)	0	0/12 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/23 (0%)	0	1/11 (9.1%)	1	0/12 (0%)	0
Neutropenia	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	0/6 (0%)	0	0/11 (0%)	0	1/11 (9.1%)	1	2/12 (16.7%)	2	0/14 (0%)	0	2/13 (15.4%)	3	1/14 (7.1%)	2	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0
Cardiac disorders
Tachycardia	0/3 (0%)	0	0/3 (0%)	0	2/9 (22.2%)	3	0/10 (0%)	0	0/6 (0%)	0	1/11 (9.1%)	1	0/11 (0%)	0	0/12 (0%)	0	1/14 (7.1%)	2	0/13 (0%)	0	1/14 (7.1%)	2	1/23 (4.3%)	3	0/11 (0%)	0	0/12 (0%)	0
Palpitations	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	0/6 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	2/12 (16.7%)	2	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0
atrioventricular block second degree	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	0/6 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	1/12 (8.3%)	1	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0
Prinzmetal angina	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	0/6 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	1/14 (7.1%)	1	0/13 (0%)	0	0/14 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0
Acute myocardial infarction	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	0/6 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	1/14 (7.1%)	1	0/13 (0%)	0	0/14 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0
Congenital, familial and genetic disorders
Buried penis syndrome	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	0/6 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	1/12 (8.3%)	1
Ear and labyrinth disorders
Tinnitus	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	0/6 (0%)	0	1/11 (9.1%)	3	0/11 (0%)	0	0/12 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0
Ear pain	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	0/6 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	1/14 (7.1%)	3	1/13 (7.7%)	1	0/14 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0
Eye disorders
Eye pain	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	0/6 (0%)	0	0/11 (0%)	0	1/11 (9.1%)	1	0/12 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0
Swelling of eyelid	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	0/6 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	1/12 (8.3%)	2	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0
Gastrointestinal disorders
Diarrhoea	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	1/10 (10%)	1	0/6 (0%)	0	0/11 (0%)	0	1/11 (9.1%)	1	1/12 (8.3%)	1	2/14 (14.3%)	3	2/13 (15.4%)	2	0/14 (0%)	0	4/23 (17.4%)	4	3/11 (27.3%)	5	1/12 (8.3%)	1
Stomatitis	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	1/6 (16.7%)	1	0/11 (0%)	0	0/11 (0%)	0	3/12 (25%)	3	3/14 (21.4%)	4	1/13 (7.7%)	1	4/14 (28.6%)	5	0/23 (0%)	0	1/11 (9.1%)	3	0/12 (0%)	0
Vomiting	0/3 (0%)	0	0/3 (0%)	0	1/9 (11.1%)	1	1/10 (10%)	1	1/6 (16.7%)	1	0/11 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	1/14 (7.1%)	1	0/13 (0%)	0	0/14 (0%)	0	1/23 (4.3%)	1	0/11 (0%)	0	0/12 (0%)	0
Paraesthesia oral	0/3 (0%)	0	0/3 (0%)	0	1/9 (11.1%)	1	0/10 (0%)	0	0/6 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0
Toothache	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	1/10 (10%)	1	0/6 (0%)	0	0/11 (0%)	0	1/11 (9.1%)	1	0/12 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	1/23 (4.3%)	1	0/11 (0%)	0	1/12 (8.3%)	1
Nausea	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	1/6 (16.7%)	1	0/11 (0%)	0	0/11 (0%)	0	1/12 (8.3%)	1	1/14 (7.1%)	1	1/13 (7.7%)	1	0/14 (0%)	0	3/23 (13%)	3	1/11 (9.1%)	2	1/12 (8.3%)	1
Bowel movement irregularity	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	1/6 (16.7%)	1	0/11 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0
Dyspepsia	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	1/6 (16.7%)	1	0/11 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	1/14 (7.1%)	1	0/13 (0%)	0	1/14 (7.1%)	1	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0
Oesophageal oedema	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	0/6 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/23 (0%)	0	1/11 (9.1%)	1	0/12 (0%)	0
Gastrooesophageal reflux disease	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	0/6 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	1/12 (8.3%)	1	0/14 (0%)	0	0/13 (0%)	0	1/14 (7.1%)	1	0/23 (0%)	0	0/11 (0%)	0	1/12 (8.3%)	1
Lip swelling	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	0/6 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	1/12 (8.3%)	1	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	1/23 (4.3%)	1	0/11 (0%)	0	0/12 (0%)	0
Pancreatitis acute	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	0/6 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	1/12 (8.3%)	1	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0
Abdominal pain	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	0/6 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	1/12 (8.3%)	1	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0
Oral mucosa haematoma	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	0/6 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	1/12 (8.3%)	1	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0
Aphthous ulcer	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	0/6 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	1/12 (8.3%)	2	3/14 (21.4%)	3	1/13 (7.7%)	1	2/14 (14.3%)	4	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0
Dental caries	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	0/6 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	1/12 (8.3%)	1	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0
Gingival pain	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	0/6 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	1/14 (7.1%)	1	0/13 (0%)	0	0/14 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0
Dry mouth	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	0/6 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/14 (0%)	0	1/13 (7.7%)	1	0/14 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0
Constipation	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	0/6 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/14 (0%)	0	1/13 (7.7%)	1	0/14 (0%)	0	0/23 (0%)	0	1/11 (9.1%)	1	0/12 (0%)	0
Diverticulum	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	0/6 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	1/14 (7.1%)	1	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0
Mouth ulceration	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	0/6 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	1/14 (7.1%)	1	0/23 (0%)	0	2/11 (18.2%)	2	1/12 (8.3%)	2
Oesophagitis	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	0/6 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/23 (0%)	0	1/11 (9.1%)	1	0/12 (0%)	0
Pancreatic atrophy	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	0/6 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/23 (0%)	0	1/11 (9.1%)	1	0/12 (0%)	0
Barrett's oesophagus	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	0/6 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/23 (0%)	0	1/11 (9.1%)	1	0/12 (0%)	0
Oesophageal stenosis	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	0/6 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/23 (0%)	0	1/11 (9.1%)	1	0/12 (0%)	0
General disorders
Chest discomfort	0/3 (0%)	0	0/3 (0%)	0	1/9 (11.1%)	1	0/10 (0%)	0	0/6 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/14 (0%)	0	1/13 (7.7%)	1	0/14 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0
Oedema peripheral	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	0/6 (0%)	0	1/11 (9.1%)	2	1/11 (9.1%)	1	2/12 (16.7%)	2	1/14 (7.1%)	1	0/13 (0%)	0	1/14 (7.1%)	2	1/23 (4.3%)	1	1/11 (9.1%)	1	1/12 (8.3%)	1
Infusion site extravasation	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	0/6 (0%)	0	1/11 (9.1%)	1	0/11 (0%)	0	0/12 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0
Catheter site pain	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	0/6 (0%)	0	0/11 (0%)	0	1/11 (9.1%)	1	0/12 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0
Pain	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	0/6 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	3/14 (21.4%)	4	0/13 (0%)	0	0/14 (0%)	0	1/23 (4.3%)	1	0/11 (0%)	0	1/12 (8.3%)	1
Pyrexia	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	0/6 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	1/14 (7.1%)	1	0/13 (0%)	0	0/14 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0
Chills	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	0/6 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/14 (0%)	0	1/13 (7.7%)	1	1/14 (7.1%)	1	1/23 (4.3%)	2	0/11 (0%)	0	0/12 (0%)	0
Fatigue	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	0/6 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	2/14 (14.3%)	3	0/23 (0%)	0	1/11 (9.1%)	1	0/12 (0%)	0
Malaise	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	0/6 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	1/14 (7.1%)	1	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0
Secretion discharge	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	0/6 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	1/14 (7.1%)	2	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0
Chest pain	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	0/6 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	1/14 (7.1%)	1	0/23 (0%)	0	1/11 (9.1%)	2	0/12 (0%)	0
Feeling hot	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	0/6 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/23 (0%)	0	1/11 (9.1%)	1	0/12 (0%)	0
Hepatobiliary disorders
Cholecystitis	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	0/6 (0%)	0	0/11 (0%)	0	1/11 (9.1%)	1	0/12 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0
Cholecystitis acute	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	0/6 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	1/12 (8.3%)	1	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0
Hepatomegaly	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	0/6 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/23 (0%)	0	1/11 (9.1%)	1	0/12 (0%)	0
Immune system disorders
Anaphylactic reaction	1/3 (33.3%)	1	0/3 (0%)	0	1/9 (11.1%)	1	0/10 (0%)	0	0/6 (0%)	0	0/11 (0%)	0	1/11 (9.1%)	1	1/12 (8.3%)	1	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	1/23 (4.3%)	1	0/11 (0%)	0	0/12 (0%)	0
Anaphylactic shock	0/3 (0%)	0	1/3 (33.3%)	1	0/9 (0%)	0	0/10 (0%)	0	0/6 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0
Seasonal allergy	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	0/6 (0%)	0	1/11 (9.1%)	1	0/11 (0%)	0	0/12 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0
Infections and infestations
Upper respiratory tract infection	0/3 (0%)	0	1/3 (33.3%)	1	1/9 (11.1%)	1	1/10 (10%)	1	0/6 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	1/12 (8.3%)	1	0/14 (0%)	0	3/13 (23.1%)	4	0/14 (0%)	0	3/23 (13%)	3	1/11 (9.1%)	1	0/12 (0%)	0
Rhinitis	0/3 (0%)	0	0/3 (0%)	0	1/9 (11.1%)	1	0/10 (0%)	0	0/6 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0
Sinusitis	0/3 (0%)	0	0/3 (0%)	0	1/9 (11.1%)	1	0/10 (0%)	0	0/6 (0%)	0	0/11 (0%)	0	1/11 (9.1%)	1	0/12 (0%)	0	1/14 (7.1%)	1	0/13 (0%)	0	1/14 (7.1%)	3	1/23 (4.3%)	3	0/11 (0%)	0	0/12 (0%)	0
Cellulitis	0/3 (0%)	0	0/3 (0%)	0	1/9 (11.1%)	1	0/10 (0%)	0	0/6 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	1/23 (4.3%)	1	0/11 (0%)	0	1/12 (8.3%)	1
Bronchitis	0/3 (0%)	0	0/3 (0%)	0	2/9 (22.2%)	2	0/10 (0%)	0	0/6 (0%)	0	1/11 (9.1%)	1	0/11 (0%)	0	0/12 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	1/14 (7.1%)	1	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0
Influenza	0/3 (0%)	0	0/3 (0%)	0	1/9 (11.1%)	1	0/10 (0%)	0	0/6 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	1/23 (4.3%)	1	0/11 (0%)	0	0/12 (0%)	0
Skin infection	0/3 (0%)	0	0/3 (0%)	0	1/9 (11.1%)	1	0/10 (0%)	0	0/6 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0
Nasopharyngitis	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	1/6 (16.7%)	1	0/11 (0%)	0	1/11 (9.1%)	1	0/12 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/23 (0%)	0	1/11 (9.1%)	1	0/12 (0%)	0
Laryngitis	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	1/6 (16.7%)	1	0/11 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0
Gingivitis	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	0/6 (0%)	0	1/11 (9.1%)	1	0/11 (0%)	0	0/12 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0
Trichomoniasis	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	0/6 (0%)	0	0/11 (0%)	0	1/11 (9.1%)	1	0/12 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0
urinary tract infection	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	0/6 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	1/12 (8.3%)	1	1/14 (7.1%)	1	0/13 (0%)	0	0/14 (0%)	0	1/23 (4.3%)	1	0/11 (0%)	0	0/12 (0%)	0
Tooth abscess	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	0/6 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	1/14 (7.1%)	1	0/13 (0%)	0	0/14 (0%)	0	1/23 (4.3%)	1	0/11 (0%)	0	0/12 (0%)	0
viral upper respiratory tract infection	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	0/6 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	2/14 (14.3%)	2	1/13 (7.7%)	1	0/14 (0%)	0	0/23 (0%)	0	1/11 (9.1%)	1	0/12 (0%)	0
Folliculitis	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	0/6 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	1/14 (7.1%)	1	1/13 (7.7%)	1	0/14 (0%)	0	1/23 (4.3%)	2	0/11 (0%)	0	0/12 (0%)	0
Prostate infection	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	0/6 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	1/14 (7.1%)	1	0/13 (0%)	0	0/14 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0
Pneumonia	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	0/6 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	1/14 (7.1%)	1	0/13 (0%)	0	0/14 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0
Tooth infection	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	0/6 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/14 (0%)	0	1/13 (7.7%)	1	0/14 (0%)	0	1/23 (4.3%)	1	0/11 (0%)	0	1/12 (8.3%)	1
otitis media	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	0/6 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/14 (0%)	0	1/13 (7.7%)	1	0/14 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0
Oral infection	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	0/6 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	1/14 (7.1%)	1	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0
Periodontitis	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	0/6 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	1/14 (7.1%)	1	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0
Pyelonephritis	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	0/6 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	1/14 (7.1%)	1	1/23 (4.3%)	1	0/11 (0%)	0	0/12 (0%)	0
Body tinea	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	0/6 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	1/14 (7.1%)	1	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0
Parotitis	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	0/6 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	1/14 (7.1%)	1	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0
Gastroenteritis	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	0/6 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	2/14 (14.3%)	2	1/23 (4.3%)	1	0/11 (0%)	0	1/12 (8.3%)	1
Pharyngitis	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	0/6 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	1/14 (7.1%)	1	1/23 (4.3%)	1	2/11 (18.2%)	3	0/12 (0%)	0
Conjunctivitis	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	0/6 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	1/14 (7.1%)	1	1/23 (4.3%)	1	0/11 (0%)	0	0/12 (0%)	0
Rash pustular	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	0/6 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	1/23 (4.3%)	1	0/11 (0%)	0	1/12 (8.3%)	1
Viral infection	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	0/6 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/23 (0%)	0	1/11 (9.1%)	1	0/12 (0%)	0
Gastroenteritis viral	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	0/6 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	1/12 (8.3%)	1
Oral herpes	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	0/6 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	1/12 (8.3%)	1
Tinea manuum	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	0/6 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	1/12 (8.3%)	1
Injury, poisoning and procedural complications
Infusion related reaction	0/3 (0%)	0	0/3 (0%)	0	1/9 (11.1%)	1	0/10 (0%)	0	0/6 (0%)	0	2/11 (18.2%)	2	1/11 (9.1%)	1	0/12 (0%)	0	1/14 (7.1%)	1	0/13 (0%)	0	0/14 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	1/12 (8.3%)	1
Skin laceration	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	1/6 (16.7%)	1	0/11 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0
Muscle strain	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	1/6 (16.7%)	1	0/11 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0
Joint injury	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	1/6 (16.7%)	1	0/11 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0
Tendon injury	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	1/6 (16.7%)	1	0/11 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0
Skin abrasion	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	0/6 (0%)	0	0/11 (0%)	0	1/11 (9.1%)	1	0/12 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	1/14 (7.1%)	1	1/23 (4.3%)	1	0/11 (0%)	0	0/12 (0%)	0
epicondylitis	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	0/6 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	1/12 (8.3%)	1	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0
Contusion	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	0/6 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	1/14 (7.1%)	1	0/13 (0%)	0	0/14 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0
Hand fracture	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	0/6 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/14 (0%)	0	1/13 (7.7%)	1	0/14 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0
Ear canal abrasion	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	0/6 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	1/14 (7.1%)	1	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0
Thermal burn	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	0/6 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	1/14 (7.1%)	1	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0
Post-traumatic neck syndrome	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	0/6 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	1/14 (7.1%)	1	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0
Ligament rupture	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	0/6 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	1/14 (7.1%)	1	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0
Ligament sprain	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	0/6 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	2/23 (8.7%)	3	0/11 (0%)	0	0/12 (0%)	0
Arthropod bite	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	0/6 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	1/23 (4.3%)	1	1/11 (9.1%)	1	0/12 (0%)	0
Investigations
Weight increased	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	1/6 (16.7%)	1	0/11 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0
Blood triglycerides increased	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	1/6 (16.7%)	1	0/11 (0%)	0	0/11 (0%)	0	1/12 (8.3%)	1	1/14 (7.1%)	1	2/13 (15.4%)	2	2/14 (14.3%)	2	3/23 (13%)	4	0/11 (0%)	0	2/12 (16.7%)	2
blood creatinine increased	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	0/6 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	1/12 (8.3%)	1	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0
Hepatic enzyme increased	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	0/6 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	1/12 (8.3%)	1	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0
Electrocardiogram QT prolonged	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	0/6 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	1/12 (8.3%)	1	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	1/23 (4.3%)	4	0/11 (0%)	0	0/12 (0%)	0
Alanine aminotransferase increased	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	0/6 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	1/14 (7.1%)	1	0/13 (0%)	0	0/14 (0%)	0	0/23 (0%)	0	1/11 (9.1%)	1	0/12 (0%)	0
aspartate aminotransferase increased	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	0/6 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	1/14 (7.1%)	1	0/13 (0%)	0	0/14 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0
Electrocardiogram T wave abnormal	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	0/6 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	1/14 (7.1%)	1	0/13 (0%)	0	0/14 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0
Heart rate increased	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	0/6 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/14 (0%)	0	1/13 (7.7%)	1	0/14 (0%)	0	1/23 (4.3%)	1	0/11 (0%)	0	0/12 (0%)	0
Blood pressure diastolic increased	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	0/6 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/14 (0%)	0	1/13 (7.7%)	1	0/14 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0
Blood pressure increased	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	0/6 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	1/12 (8.3%)	1	1/14 (7.1%)	1	0/13 (0%)	0	1/14 (7.1%)	1	1/23 (4.3%)	1	0/11 (0%)	0	0/12 (0%)	0
Semen volume decreased	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	0/6 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/23 (0%)	0	1/11 (9.1%)	1	0/12 (0%)	0
Low density lipoprotein increased	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	0/6 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	1/12 (8.3%)	1
Metabolism and nutrition disorders
Gout flare	3/3 (100%)	3	0/3 (0%)	0	2/9 (22.2%)	2	2/10 (20%)	2	2/6 (33.3%)	4	2/11 (18.2%)	3	4/11 (36.4%)	8	4/12 (33.3%)	10	6/14 (42.9%)	15	4/13 (30.8%)	10	4/14 (28.6%)	10	8/23 (34.8%)	23	5/11 (45.5%)	9	5/12 (41.7%)	21
Hyperglycaemia	0/3 (0%)	0	0/3 (0%)	0	1/9 (11.1%)	1	0/10 (0%)	0	2/6 (33.3%)	2	1/11 (9.1%)	1	1/11 (9.1%)	1	1/12 (8.3%)	1	1/14 (7.1%)	1	1/13 (7.7%)	1	0/14 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0
Hypophosphataemia	0/3 (0%)	0	0/3 (0%)	0	4/9 (44.4%)	5	0/10 (0%)	0	0/6 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/14 (0%)	0	1/13 (7.7%)	1	0/14 (0%)	0	0/23 (0%)	0	1/11 (9.1%)	1	0/12 (0%)	0
Hyperlipidaemia	0/3 (0%)	0	0/3 (0%)	0	1/9 (11.1%)	1	0/10 (0%)	0	1/6 (16.7%)	1	0/11 (0%)	0	1/11 (9.1%)	1	0/12 (0%)	0	1/14 (7.1%)	1	0/13 (0%)	0	0/14 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	1/12 (8.3%)	2
Hypertriglyceridaemia	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	2/6 (33.3%)	2	1/11 (9.1%)	1	1/11 (9.1%)	1	0/12 (0%)	0	2/14 (14.3%)	6	3/13 (23.1%)	4	1/14 (7.1%)	2	1/23 (4.3%)	1	2/11 (18.2%)	3	1/12 (8.3%)	2
Hypokalaemia	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	0/6 (0%)	0	2/11 (18.2%)	2	0/11 (0%)	0	1/12 (8.3%)	1	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0
Type 2 diabetes mellitus	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	0/6 (0%)	0	1/11 (9.1%)	1	0/11 (0%)	0	0/12 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	1/23 (4.3%)	1	0/11 (0%)	0	0/12 (0%)	0
Decreased appetite	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	0/6 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	1/12 (8.3%)	1	0/14 (0%)	0	0/13 (0%)	0	1/14 (7.1%)	1	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0
Hypercholesterolaemia	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	0/6 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	1/14 (7.1%)	1	0/13 (0%)	0	0/14 (0%)	0	1/23 (4.3%)	1	0/11 (0%)	0	0/12 (0%)	0
Vitamin D deficiency	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	0/6 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	1/14 (7.1%)	1	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0
Dehydration	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	0/6 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	1/14 (7.1%)	1	1/23 (4.3%)	1	1/11 (9.1%)	2	0/12 (0%)	0
Increased appetite	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	0/6 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	2/23 (8.7%)	2	3/11 (27.3%)	3	0/12 (0%)	0
Musculoskeletal and connective tissue disorders
Musculoskeletal stiffness	0/3 (0%)	0	1/3 (33.3%)	1	0/9 (0%)	0	0/10 (0%)	0	0/6 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	1/14 (7.1%)	2	1/13 (7.7%)	2	0/14 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	1/12 (8.3%)	1
Flank pain	0/3 (0%)	0	0/3 (0%)	0	1/9 (11.1%)	1	0/10 (0%)	0	1/6 (16.7%)	2	0/11 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0
Osteoarthritis	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	1/10 (10%)	1	0/6 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	1/14 (7.1%)	1	0/13 (0%)	0	0/14 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0
Patellofemoral pain syndrome	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	1/10 (10%)	1	0/6 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0
Back pain	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	2/6 (33.3%)	3	0/11 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	1/14 (7.1%)	2	0/13 (0%)	0	1/14 (7.1%)	1	0/23 (0%)	0	0/11 (0%)	0	2/12 (16.7%)	2
Pain in extremity	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	1/6 (16.7%)	1	0/11 (0%)	0	3/11 (27.3%)	4	2/12 (16.7%)	2	2/14 (14.3%)	2	0/13 (0%)	0	0/14 (0%)	0	2/23 (8.7%)	3	0/11 (0%)	0	0/12 (0%)	0
Arthralgia	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	1/6 (16.7%)	1	2/11 (18.2%)	3	2/11 (18.2%)	2	2/12 (16.7%)	3	1/14 (7.1%)	2	0/13 (0%)	0	2/14 (14.3%)	2	2/23 (8.7%)	2	2/11 (18.2%)	3	1/12 (8.3%)	1
Joint effusion	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	1/6 (16.7%)	1	0/11 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	1/12 (8.3%)	1
Musculoskeletal Pain	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	0/6 (0%)	0	0/11 (0%)	0	1/11 (9.1%)	1	0/12 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	1/12 (8.3%)	1
myalgia	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	0/6 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	2/12 (16.7%)	2	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	1/23 (4.3%)	1	0/11 (0%)	0	0/12 (0%)	0
Muscle spasms	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	0/6 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	1/12 (8.3%)	2	1/14 (7.1%)	1	1/13 (7.7%)	1	2/14 (14.3%)	2	2/23 (8.7%)	2	0/11 (0%)	0	0/12 (0%)	0
Plantar fasciitis	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	0/6 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	1/12 (8.3%)	1	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0
Tendonitis	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	0/6 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	1/12 (8.3%)	1	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0
Metatarsalgia	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	0/6 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	1/12 (8.3%)	1	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0
Joint stiffness	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	0/6 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	1/14 (7.1%)	3	0/13 (0%)	0	0/14 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	1/12 (8.3%)	1
Joint swelling	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	0/6 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	1/14 (7.1%)	1	0/13 (0%)	0	0/14 (0%)	0	0/23 (0%)	0	1/11 (9.1%)	1	0/12 (0%)	0
Neck pain	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	0/6 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	1/14 (7.1%)	1	0/23 (0%)	0	0/11 (0%)	0	1/12 (8.3%)	1
Groin pain	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	0/6 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/23 (0%)	0	1/11 (9.1%)	2	1/12 (8.3%)	1
Limb discomfort	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	0/6 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/23 (0%)	0	1/11 (9.1%)	1	0/12 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Seborrhoeic keratosis	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	0/6 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	1/14 (7.1%)	1	0/13 (0%)	0	0/14 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0
Nervous system disorders
Headache	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	4/10 (40%)	4	1/6 (16.7%)	1	1/11 (9.1%)	1	3/11 (27.3%)	5	3/12 (25%)	6	3/14 (21.4%)	5	1/13 (7.7%)	2	3/14 (21.4%)	4	4/23 (17.4%)	8	3/11 (27.3%)	8	3/12 (25%)	3
Paraesthesia	0/3 (0%)	0	0/3 (0%)	0	1/9 (11.1%)	1	0/10 (0%)	0	0/6 (0%)	0	0/11 (0%)	0	1/11 (9.1%)	1	2/12 (16.7%)	2	0/14 (0%)	0	1/13 (7.7%)	1	0/14 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0
Hypogeusia	0/3 (0%)	0	0/3 (0%)	0	1/9 (11.1%)	1	0/10 (0%)	0	0/6 (0%)	0	1/11 (9.1%)	2	0/11 (0%)	0	0/12 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0
Presyncope	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	2/6 (33.3%)	2	0/11 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0
Sciatica	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	0/6 (0%)	0	1/11 (9.1%)	1	0/11 (0%)	0	0/12 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/23 (0%)	0	1/11 (9.1%)	1	1/12 (8.3%)	1
Formication	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	0/6 (0%)	0	1/11 (9.1%)	1	0/11 (0%)	0	0/12 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0
Dysgeusia	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	0/6 (0%)	0	1/11 (9.1%)	2	0/11 (0%)	0	0/12 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	2/14 (14.3%)	2	2/23 (8.7%)	4	0/11 (0%)	0	0/12 (0%)	0
Dizziness	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	0/6 (0%)	0	0/11 (0%)	0	1/11 (9.1%)	1	0/12 (0%)	0	1/14 (7.1%)	1	0/13 (0%)	0	0/14 (0%)	0	1/23 (4.3%)	1	0/11 (0%)	0	1/12 (8.3%)	1
Migraine	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	0/6 (0%)	0	0/11 (0%)	0	1/11 (9.1%)	1	0/12 (0%)	0	0/14 (0%)	0	1/13 (7.7%)	1	0/14 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0
burning sensation	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	0/6 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	1/12 (8.3%)	1	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0
Diabetic neuropathy	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	0/6 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	1/12 (8.3%)	1	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0
Dysaesthesia	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	0/6 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	1/14 (7.1%)	1	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0
Depressed level of consciousness	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	0/6 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	1/14 (7.1%)	1	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0
Syncope	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	0/6 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	1/14 (7.1%)	1	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0
sinus headache	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	0/6 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	1/14 (7.1%)	1	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0
Memory impairment	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	0/6 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/23 (0%)	0	1/11 (9.1%)	1	0/12 (0%)	0
Aphasia	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	0/6 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/23 (0%)	0	1/11 (9.1%)	2	0/12 (0%)	0
Psychiatric disorders
Anxiety	0/3 (0%)	0	0/3 (0%)	0	1/9 (11.1%)	1	0/10 (0%)	0	0/6 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	1/12 (8.3%)	1	1/14 (7.1%)	1	0/13 (0%)	0	0/14 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0
Stress	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	1/6 (16.7%)	1	0/11 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0
Insomnia	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	0/6 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/14 (0%)	0	1/13 (7.7%)	1	1/14 (7.1%)	1	0/23 (0%)	0	2/11 (18.2%)	2	0/12 (0%)	0
Nervousness	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	0/6 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/23 (0%)	0	1/11 (9.1%)	2	0/12 (0%)	0
Libido decreased	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	0/6 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/23 (0%)	0	1/11 (9.1%)	1	0/12 (0%)	0
Renal and urinary disorders
Micturition urgency	0/3 (0%)	0	0/3 (0%)	0	1/9 (11.1%)	1	0/10 (0%)	0	0/6 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	1/12 (8.3%)	1	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0
Chromaturia	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	1/6 (16.7%)	2	1/11 (9.1%)	4	0/11 (0%)	0	0/12 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0
Pollakiuria	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	1/6 (16.7%)	1	0/11 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0
Urine odour abnormal	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	0/6 (0%)	0	1/11 (9.1%)	6	0/11 (0%)	0	0/12 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0
Nocturia	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	0/6 (0%)	0	0/11 (0%)	0	1/11 (9.1%)	1	0/12 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0
acute kidney injury	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	0/6 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	1/12 (8.3%)	1	0/14 (0%)	0	0/13 (0%)	0	1/14 (7.1%)	1	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0
Nephrolithiasis	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	0/6 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	1/12 (8.3%)	1
Reproductive system and breast disorders
Ovarian cyst	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	0/6 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	1/14 (7.1%)	1	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0
Ejaculation failure	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	0/6 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	1/14 (7.1%)	1	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0
Testicular pain	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	0/6 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/23 (0%)	0	1/11 (9.1%)	1	0/12 (0%)	0
Prostatitis	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	0/6 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	1/12 (8.3%)	1
Benign prostatic hyperplasia	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	0/6 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	1/12 (8.3%)	1
Respiratory, thoracic and mediastinal disorders
Asthma	0/3 (0%)	0	0/3 (0%)	0	1/9 (11.1%)	1	0/10 (0%)	0	0/6 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	1/14 (7.1%)	1	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0
Cough	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	1/10 (10%)	1	0/6 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	2/23 (8.7%)	2	1/11 (9.1%)	1	0/12 (0%)	0
Pleurisy	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	0/6 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	1/12 (8.3%)	1	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0
Dysphonia	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	0/6 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	1/14 (7.1%)	5	0/13 (0%)	0	0/14 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0
Epistaxis	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	0/6 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/14 (0%)	0	1/13 (7.7%)	1	2/14 (14.3%)	2	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0
Oropharyngeal pain	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	0/6 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	1/14 (7.1%)	1	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0
Sinus congestion	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	0/6 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	1/14 (7.1%)	1	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0
Haemoptysis	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	0/6 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	1/14 (7.1%)	1	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0
Dyspnoea	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	0/6 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	1/14 (7.1%)	1	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0
Skin and subcutaneous tissue disorders
Rash	0/3 (0%)	0	0/3 (0%)	0	1/9 (11.1%)	1	0/10 (0%)	0	0/6 (0%)	0	0/11 (0%)	0	1/11 (9.1%)	1	2/12 (16.7%)	2	0/14 (0%)	0	0/13 (0%)	0	1/14 (7.1%)	1	2/23 (8.7%)	3	1/11 (9.1%)	1	0/12 (0%)	0
Pruritus	0/3 (0%)	0	1/3 (33.3%)	1	0/9 (0%)	0	0/10 (0%)	0	0/6 (0%)	0	0/11 (0%)	0	1/11 (9.1%)	1	0/12 (0%)	0	1/14 (7.1%)	1	0/13 (0%)	0	1/14 (7.1%)	1	1/23 (4.3%)	1	0/11 (0%)	0	0/12 (0%)	0
Dermatitis contact	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	1/6 (16.7%)	1	0/11 (0%)	0	1/11 (9.1%)	1	0/12 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	1/23 (4.3%)	1	0/11 (0%)	0	0/12 (0%)	0
Hand dermatitis	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	0/6 (0%)	0	0/11 (0%)	0	1/11 (9.1%)	1	0/12 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0
alopecia	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	0/6 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	1/12 (8.3%)	1	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0
Rash papular	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	0/6 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	1/12 (8.3%)	1	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0
Dermatitis allergic	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	0/6 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	1/12 (8.3%)	1	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	1/23 (4.3%)	1	0/11 (0%)	0	1/12 (8.3%)	1
Night sweats	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	0/6 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	1/14 (7.1%)	1	0/13 (0%)	0	0/14 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0
Urticaria	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	0/6 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	2/14 (14.3%)	2	0/13 (0%)	0	0/14 (0%)	0	1/23 (4.3%)	1	0/11 (0%)	0	0/12 (0%)	0
Actinic keratosis	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	0/6 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	1/14 (7.1%)	1	0/13 (0%)	0	0/14 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0
Rash maculo-papular	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	0/6 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/14 (0%)	0	1/13 (7.7%)	1	1/14 (7.1%)	1	1/23 (4.3%)	3	0/11 (0%)	0	0/12 (0%)	0
Rash pruritic	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	0/6 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	1/14 (7.1%)	1	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0
Ecchymosis	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	0/6 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/23 (0%)	0	1/11 (9.1%)	1	0/12 (0%)	0
Dermal cyst	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	0/6 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	1/12 (8.3%)	1
Vascular disorders
Flushing	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	1/10 (10%)	1	1/6 (16.7%)	1	0/11 (0%)	0	0/11 (0%)	0	1/12 (8.3%)	1	1/14 (7.1%)	3	0/13 (0%)	0	1/14 (7.1%)	3	2/23 (8.7%)	5	1/11 (9.1%)	2	2/12 (16.7%)	3
Hypertension	0/3 (0%)	0	1/3 (33.3%)	1	0/9 (0%)	0	0/10 (0%)	0	1/6 (16.7%)	1	0/11 (0%)	0	0/11 (0%)	0	1/12 (8.3%)	1	1/14 (7.1%)	1	1/13 (7.7%)	1	0/14 (0%)	0	2/23 (8.7%)	2	0/11 (0%)	0	0/12 (0%)	0
Vasospasm	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	0/6 (0%)	0	0/11 (0%)	0	1/11 (9.1%)	2	0/12 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0
Phlebitis superficial	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	0/6 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	1/14 (7.1%)	1	0/13 (0%)	0	0/14 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0
Varicose vein	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	0/6 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	1/14 (7.1%)	1	0/13 (0%)	0	0/14 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0
Hypotension	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	0/6 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/23 (0%)	0	1/11 (9.1%)	1	1/12 (8.3%)	1
Hot flash	0/3 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	0/6 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/23 (0%)	0	1/11 (9.1%)	1	0/12 (0%)	0

Limitations/Caveats

[Not Specified]

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Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.