Phase II Dose Finding Study of RDEA3170 Versus Placebo in Japanese Patients With Gout or Asymptomatic Hyperuricemia

• Sponsor: AstraZeneca (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02078219
• Collaborator: Ardea Biosciences, Inc. (Industry)
• Enrollment: 204
• Locations: 14
• Arms: 5
• Actual Duration (Months): 14.2
• Patients Per Site: 14.6
• Patients Per Site Per Month: 1

Study Details

Study Description

Brief Summary

This study is to examine the hypothesis that administration of RDEA3170 to Japanese patients with gout or asymptomatic hyperuricemia in doses of 5 mg, 7.5 mg, 10 mg, 12.5 mg and 15 mg once daily, respectively will result in greater reduction of sUA compared to placebo.

Condition or Disease	Intervention/Treatment	Phase
Gout and Hyperuricemia	Drug: RDEA3170; Drug: Allopurinol; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 204 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Randomized, Double-Blind, Multicenter, Placebo-Controlled, Parallel Group, 24-Week Phase II Study to Evaluate Efficacy and Safety of RDEA3170 5 mg, 7.5 mg, 10 mg, 12.5 mg and 15 mg Versus Placebo and Open-Label Allopurinol 200 mg as a Reference Arm in Japanese Patients With Gout or Asymptomatic Hyperuricemia
• Actual Study Start Date: Jan 5, 2014
• Actual Primary Completion Date: Mar 13, 2015
• Actual Study Completion Date: Mar 13, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: RDEA3170 1 RDEA3170 5mg followed by RDEA3170 7.5mg	Drug: RDEA3170; Oral Treatment
Experimental: RDEA3170 2 RDEA3170 10mg followed by RDEA3170 12.5mg	Drug: RDEA3170; Oral Treatment
Experimental: RDEA3170 3 RDEA3170 12.5mg followed by RDEA3170 15mg	Drug: RDEA3170; Oral Treatment
Placebo Comparator: RDEA3170 4 RDEA3170 Placebo	Drug: Placebo; Oral Treatment
Other: Allopurinol Allopurinol 200mg	Drug: Allopurinol; Oral Treatment; Other Names: Allopurinol 200mg Sawai

Outcome Measures

Primary Outcome Measures

1. Percent Changes of Serum Uric Acid Levels From Baseline Levels [Baseline and Week 16]

   The primary objective of the study is to compare percent changes of serum uric acid levels from baseline levels after 16 weeks of dosing between RDEA3170 treatment groups and the placebo treatment group.

Secondary Outcome Measures

1. Percentage of Subjects With a Serum Uric Acid Level ≤6.0 mg/dL [Weeks 1,2,4,6,8,10,12,16,18,20,24]

   To compare the percentage of subjects whose serum uric acid levels are ≤ 6.0 mg/dL between RDEA3170 treatment groups and the placebo treatment group at each study visit

2. Percent Change in sUA [Baseline, Weeks 1,2,4,6,8,10,12,16,18,20,24]

   To compare percent change in sUA at each study visit.

3. Absolute Change of Serum Uric Acid Levels From Baseline Levels [Baseline, Weeks 1,2,4,6,8,10,12,16,18,20,24]

   To compare the absolute change of serum uric acid levels from baseline levels

Eligibility Criteria

Criteria

• Ages Eligible for Study: 20 Years to 70 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Subject meets any of the following criteria and with sUA ≤10.0 mg/dL:

1. sUA level of >7.0 mg/dL at 7 days prior to baseline with gout;

2. sUA level of ≥8.0 mg/dL at 7 days prior to baseline without gout but with complications (hypertension, ischemic heart disease, diabetes, metabolic syndrome);

3. sUA level of ≥9.0 mg/dL at 7 days prior to baseline without gout and complications.

Exclusion Criteria:

• Subject with an acute gout flare that has not resolved at least 14 days prior to the baseline visit.

• Subject has a history or suspicion of kidney stones.

• Subject has an estimated creatinine clearance <60 mL/min calculated by the Cockcroft Gault formula

• Subject is receiving strong or moderate CYP3A inhibitors

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Chofu-shi		Japan	182-0006
2	Research Site	Fukuoka-shi		Japan	812-0027
3	Research Site	Fukuoka-shi		Japan	819-0006
4	Research Site	Fukuoka-shi		Japan	819-8551
5	Research Site	Kitakyushu-shi		Japan	807-0857
6	Research Site	Matsudo-shi		Japan	270-0021
7	Research Site	Noda-shi		Japan	278-8501
8	Research Site	Ota-ku		Japan	144-0034
9	Research Site	Saitama-shi		Japan	339-8521
10	Research Site	Sendai-shi		Japan	980-0011
11	Research Site	Sendai-shi		Japan	981-0923
12	Research Site	Sendai-shi		Japan	983-0039
13	Research Site	Sendai-shi		Japan	983-0835
14	Research Site	Shinagawa-ku		Japan	141-6003

Sponsors and Collaborators

• AstraZeneca
• Ardea Biosciences, Inc.

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: AstraZeneca
• ClinicalTrials.gov Identifier: NCT02078219
• Other Study ID Numbers: D5491C00001; RDEA3170-203
• First Posted: Mar 5, 2014
• Last Update Posted: Sep 24, 2019
• Last Verified: Aug 1, 2019

• Additional relevant MeSH terms: Gout; Hyperuricemia; Allopurinol; Verinurad

Study Results

Participant Flow

Recruitment Details	Of the 381 subjects who were screened in the study, 204 were randomized into one of the treatment groups. All 204 randomized subjects received at least 1 dose of randomized study medication. The first patient was enrolled on 11 March 2014 and the last enrolled patient completed the Last visit on 13 March 2015.
Pre-assignment Detail	204 were randomized into one of the following treatment groups; allopurinol, placebo, RDEA3170 Group 1, Group 2 and Group 3. Of the enrolled subjects, 177 were withdrawn prior to randomization because of 'eligibility criteria not fulfill' (176 subjects) or 'patient decision' (1 subject).

Arm/Group Title	Allopurinol 200 mg Treatment Group	RDEA3170 Placebo Treatment Group	RDEA3170 Treatment Group 1	RDEA3170 Treatment Group 2	RDEA3170 Treatment Group 3
Arm/Group Description	100 mg qd for 4 weeks and allopurinol 100 mg bid for 20 weeks	RDEA3170 matching placebo qd for 24 weeks	RDEA3170 2.5 mg once daily (qd) for 4 weeks followed by RDEA3170 5 mg qd for 12 weeks followed by RDEA3170 7.5 mg qd for 8 weeks	RDEA3170 2.5 mg qd for 4 weeks followed by RDEA3170 5 mg qd for 4 weeks followed by RDEA3170 10 mg qd for 8 weeks followed by RDEA3170 12.5 mg qd for 8 weeks	RDEA3170 2.5 mg qd for 4 weeks followed by RDEA3170 5 mg qd for 4 weeks followed by RDEA3170 12.5 mg qd for 8 weeks followed by RDEA3170 15 mg qd for 8 weeks
Period Title: Overall Study
STARTED	41	40	41	41	41
COMPLETED	38	36	35	37	39
NOT COMPLETED	3	4	6	4	2

Baseline Characteristics

Arm/Group Title	Allopurinol 200 mg Treatment Group	RDEA3170 Placebo Treatment Group	RDEA3170 Treatment Group 1	RDEA3170 Treatment Group 2	RDEA3170 Treatment Group 3	Total
Arm/Group Description	100 mg qd for 4 weeks and allopurinol 100 mg bid for 20 weeks	RDEA3170 matching placebo qd for 24 weeks	RDEA3170 2.5 mg once daily (qd) for 4 weeks followed by RDEA3170 5 mg qd for 12 weeks followed by RDEA3170 7.5 mg qd for 8 weeks	RDEA3170 2.5 mg qd for 4 weeks followed by RDEA3170 5 mg qd for 4 weeks followed by RDEA3170 10 mg qd for 8 weeks followed by RDEA3170 12.5 mg qd for 8 weeks	RDEA3170 2.5 mg qd for 4 weeks followed by RDEA3170 5 mg qd for 4 weeks followed by RDEA3170 12.5 mg qd for 8 weeks followed by RDEA3170 15 mg qd for 8 weeks	Total of all reporting groups
Overall Participants	41	40	41	41	41	204
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	51.0 (10.6)	54.5 (10.3)	51.3 (9.3)	52.7 (10.0)	52.3 (10.7)	52.3 (10.2)
Sex: Female, Male (Count of Participants)
Female	0 0%	1 2.5%	0 0%	1 2.4%	2 4.9%	4 2%
Male	41 100%	39 97.5%	41 100%	40 97.6%	39 95.1%	200 98%

Outcome Measures

1. Primary Outcome

Title	Percent Changes of Serum Uric Acid Levels From Baseline Levels
Description	The primary objective of the study is to compare percent changes of serum uric acid levels from baseline levels after 16 weeks of dosing between RDEA3170 treatment groups and the placebo treatment group.
Time Frame	Baseline and Week 16

Outcome Measure Data

Analysis Population Description

Efficacy analysis set

Arm/Group Title	RDEA3170 Treatment Group 1	RDEA3170 Treatment Group 2	RDEA3170 Treatment Group 3	RDEA3170 Placebo Treatment Group	Allopurinol 200 mg Treatment Group
Arm/Group Description	RDEA3170 2.5 mg once daily (qd) for 4 weeks followed by RDEA3170 5 mg qd for 12 weeks followed by RDEA3170 7.5 mg qd for 8 weeks	RDEA3170 2.5 mg qd for 4 weeks followed by RDEA3170 5 mg qd for 4 weeks followed by RDEA3170 10 mg qd for 8 weeks followed by RDEA3170 12.5 mg qd for 8 weeks	RDEA3170 2.5 mg qd for 4 weeks followed by RDEA3170 5 mg qd for 4 weeks followed by RDEA3170 12.5 mg qd for 8 weeks followed by RDEA3170 15 mg qd for 8 weeks	RDEA3170 matching placebo qd for 24 weeks	Allopurinol 100 mg qd for 4 weeks followed by allopurinol 100 mg twice daily (bid) for 20 weeks
Measure Participants	41	41	41	40	41
Mean (Standard Deviation) [Percent change]	-30.93 (17.80)	-49.91 (18.38)	-54.32 (13.40)	-2.05 (9.29)	-39.09 (11.54)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	RDEA3170 Treatment Group 1, RDEA3170 Placebo Treatment Group
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA, LOCF
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-29.28
	Confidence Interval	(2-Sided) 95%; -36.99 to -21.57
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	RDEA3170 Treatment Group 2, RDEA3170 Placebo Treatment Group
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA, LOCF
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-49.25
	Confidence Interval	(2-Sided) 95%; -56.97 to -41.52
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	RDEA3170 Treatment Group 3, RDEA3170 Placebo Treatment Group
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA, LOCF
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-53.33
	Confidence Interval	(2-Sided) 95%; -61.00 to -45.67
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Percentage of Subjects With a Serum Uric Acid Level ≤6.0 mg/dL
Description	To compare the percentage of subjects whose serum uric acid levels are ≤ 6.0 mg/dL between RDEA3170 treatment groups and the placebo treatment group at each study visit
Time Frame	Weeks 1,2,4,6,8,10,12,16,18,20,24

Outcome Measure Data

Analysis Population Description

Efficacy analysis set

Arm/Group Title	RDEA3170 Treatment Group 1	RDEA3170 Treatment Group 2	RDEA3170 Treatment Group 3	RDEA3170 Placebo Treatment Group	Allopurinol 200 mg Treatment Group
Arm/Group Description	RDEA3170 2.5 mg once daily (qd) for 4 weeks followed by RDEA3170 5 mg qd for 12 weeks followed by RDEA3170 7.5 mg qd for 8 weeks	RDEA3170 2.5 mg qd for 4 weeks followed by RDEA3170 5 mg qd for 4 weeks followed by RDEA3170 10 mg qd for 8 weeks followed by RDEA3170 12.5 mg qd for 8 weeks	RDEA3170 2.5 mg qd for 4 weeks followed by RDEA3170 5 mg qd for 4 weeks followed by RDEA3170 12.5 mg qd for 8 weeks followed by RDEA3170 15 mg qd for 8 weeks	RDEA3170 matching placebo qd for 24 weeks	Allopurinol 100 mg qd for 4 weeks followed by allopurinol 100 mg twice daily (bid) for 20 weeks
Measure Participants	41	41	41	40	41
Week 1	26.8	31.7	39.0	0	19.5
Week 2	29.3	34.1	34.1	0	19.5
Week 4	26.8	31.7	39.0	0	17.1
Week 6	70.7	61.0	82.9	0	73.2
Week 8	53.7	56.1	78.0	0	65.9
Week 10	46.3	78.0	92.7	0	61.0
Week 12	53.7	85.4	92.7	0	75.6
Week 16	51.2	95.1	97.6	0	78.0
Week 18	63.4	92.7	95.1	0	73.2
Week 20	61.0	82.9	92.7	0	78.0
Week 24	68.3	82.9	87.8	0	75.6

3. Secondary Outcome

Title	Percent Change in sUA
Description	To compare percent change in sUA at each study visit.
Time Frame	Baseline, Weeks 1,2,4,6,8,10,12,16,18,20,24

Outcome Measure Data

Analysis Population Description

Efficacy analysis set

Arm/Group Title	RDEA3170 Treatment Group 1	RDEA3170 Treatment Group 2	RDEA3170 Treatment Group 3	RDEA3170 Placebo Treatment Group	Allopurinol 200 mg Treatment Group
Arm/Group Description	RDEA3170 2.5 mg once daily (qd) for 4 weeks followed by RDEA3170 5 mg qd for 12 weeks followed by RDEA3170 7.5 mg qd for 8 weeks	RDEA3170 2.5 mg qd for 4 weeks followed by RDEA3170 5 mg qd for 4 weeks followed by RDEA3170 10 mg qd for 8 weeks followed by RDEA3170 12.5 mg qd for 8 weeks	RDEA3170 2.5 mg qd for 4 weeks followed by RDEA3170 5 mg qd for 4 weeks followed by RDEA3170 12.5 mg qd for 8 weeks followed by RDEA3170 15 mg qd for 8 weeks	RDEA3170 matching placebo qd for 24 weeks	Allopurinol 100 mg qd for 4 weeks followed by allopurinol 100 mg twice daily (bid) for 20 weeks
Measure Participants	41	41	41	40	41
Week 1	-19.72 (10.93)	-20.29 (17.51)	-19.93 (22.98)	-0.25 (8.57)	-20.74 (7.72)
Week 2	-21.03 (11.87)	-20.28 (16.87)	-20.93 (10.68)	-0.53 (7.20)	-20.80 (9.37)
Week 4	-22.95 (10.86)	-19.66 (17.24)	-24.21 (10.69)	0.97 (8.70)	-20.60 (8.83)
Week 6	-32.05 (13.05)	-31.26 (19.83)	-35.24 (10.74)	-0.01 (9.86)	-37.06 (8.72)
Week 8	-27.94 (16.54)	-30.19 (19.22)	-32.11 (13.96)	0.55 (9.50)	-36.51 (11.14)
Week 10	-24.69 (18.81)	-37.61 (18.35)	-44.38 (12.33)	-0.27 (9.53)	-33.42 (11.28)
Week 12	-28.08 (18.22)	-45.77 (17.94)	-51.17 (16.19)	0.43 (7.89)	-37.96 (10.65)
Week 16	-30.93 (17.80)	-49.91 (18.38)	-54.32 (13.40)	-2.05 (9.29)	-39.09 (11.54)
Week 18	-32.94 (18.11)	-49.04 (19.19)	-54.70 (13.32)	-2.86 (8.55)	-38.59 (10.32)
Week 20	-32.96 (18.69)	-47.20 (21.46)	-53.60 (12.92)	-2.27 (8.76)	-38.00 (11.11)
Week 24	-35.73 (19.49)	-47.34 (21.39)	-54.46 (18.97)	-4.67 (10.36)	-37.77 (11.47)

4. Secondary Outcome

Title	Absolute Change of Serum Uric Acid Levels From Baseline Levels
Description	To compare the absolute change of serum uric acid levels from baseline levels
Time Frame	Baseline, Weeks 1,2,4,6,8,10,12,16,18,20,24

Outcome Measure Data

Analysis Population Description

Efficacy analysis set

Arm/Group Title	RDEA3170 Treatment Group 1	RDEA3170 Treatment Group 2	RDEA3170 Treatment Group 3	RDEA3170 Placebo Treatment Group	Allopurinol 200 mg Treatment Group
Arm/Group Description	RDEA3170 2.5 mg once daily (qd) for 4 weeks followed by RDEA3170 5 mg qd for 12 weeks followed by RDEA3170 7.5 mg qd for 8 weeks	RDEA3170 2.5 mg qd for 4 weeks followed by RDEA3170 5 mg qd for 4 weeks followed by RDEA3170 10 mg qd for 8 weeks followed by RDEA3170 12.5 mg qd for 8 weeks	RDEA3170 2.5 mg qd for 4 weeks followed by RDEA3170 5 mg qd for 4 weeks followed by RDEA3170 12.5 mg qd for 8 weeks followed by RDEA3170 15 mg qd for 8 weeks	RDEA3170 matching placebo qd for 24 weeks	Allopurinol 100 mg qd for 4 weeks followed by allopurinol 100 mg twice daily (bid) for 20 weeks
Measure Participants	41	41	41	40	41
Week 1	-1.68 (1.01)	-1.74 (1.48)	-1.68 (2.10)	-0.05 (0.77)	-1.82 (0.73)
Week 2	-1.81 (1.11)	-1.75 (1.45)	-1.78 (0.98)	-0.07 (0.64)	-1.83 (0.90)
Week 4	-2.01 (1.09)	-1.72 (1.48)	-2.07 (1.01)	0.06 (0.76)	-1.83 (0.89)
Week 6	-2.78 (1.34)	-2.66 (1.73)	-3.00 (1.09)	-0.04 (0.81)	-3.26 (0.93)
Week 8	-2.44 (1.48)	-2.61 (1.75)	-2.74 (1.23)	0.02 (0.85)	-3.22 (1.09)
Week 10	-2.19 (1.65)	-3.22 (1.78)	-3.75 (1.19)	-0.06 (0.79)	-2.96 (1.13)
Week 12	-2.44 (1.56)	-3.85 (1.62)	-4.33 (1.45)	0.02 (0.70)	-3.35 (1.09)
Week 16	-2.67 (1.48)	-4.24 (1.82)	-4.57 (1.28)	-0.22 (0.81)	-3.44 (1.10)
Week 18	-2.86 (1.54)	-4.17 (1.82)	-4.62 (1.27)	-0.27 (0.75)	-3.40 (1.06)
Week 20	-2.87 (1.61)	-3.98 (1.97)	-4.52 (1.15)	-0.22 (0.75)	-3.35 (1.15)
Week 24	-3.10 (1.67)	-3.99 (1.96)	-4.57 (1.64)	-0.42 (0.90)	-3.31 (1.10)

Adverse Events

Time Frame	Adverse Events and serious adverse events will be collected from the time of informed consent throughout the treatment period and the follow-up period.
Arm/Group Title	Allopurinol 200 mg Treatment Group		RDEA3170 Placebo Treatment Group		RDEA3170 Treatment Group 1		RDEA3170 Treatment Group 2		RDEA3170 Treatment Group 3
Arm/Group Description	allopurinol 100 mg qd for 4 weeks followed by allopurinol 100 mg twice daily (bid) for 20 weeks.		RDEA3170 matching placebo qd for 24 weeks		RDEA3170 2.5 mg once daily (qd) for 4 weeks followed by RDEA3170 5 mg qd for 12 weeks followed by RDEA3170 7.5 mg qd for 8 weeks		RDEA3170 2.5 mg qd for 4 weeks followed by RDEA3170 5 mg qd for 4 weeks followed by RDEA3170 10 mg qd for 8 weeks followed by RDEA3170 12.5 mg qd for 8 weeks		RDEA3170 2.5 mg qd for 4 weeks followed by RDEA3170 5 mg qd for 4 weeks followed by RDEA3170 12.5 mg qd for 8 weeks followed by RDEA3170 15 mg qd for 8 weeks
All Cause Mortality
	Allopurinol 200 mg Treatment Group		RDEA3170 Placebo Treatment Group		RDEA3170 Treatment Group 1		RDEA3170 Treatment Group 2		RDEA3170 Treatment Group 3
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Allopurinol 200 mg Treatment Group		RDEA3170 Placebo Treatment Group		RDEA3170 Treatment Group 1		RDEA3170 Treatment Group 2		RDEA3170 Treatment Group 3
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/41 (2.4%)		1/40 (2.5%)		1/41 (2.4%)		1/41 (2.4%)		0/41 (0%)
Cardiac disorders
Silent myocardial infarction	0/41 (0%)		0/40 (0%)		1/41 (2.4%)		0/41 (0%)		0/41 (0%)
Hepatobiliary disorders
Bile duct stone	1/41 (2.4%)		0/40 (0%)		0/41 (0%)		0/41 (0%)		0/41 (0%)
Injury, poisoning and procedural complications
Hand fracture	0/41 (0%)		1/40 (2.5%)		0/41 (0%)		0/41 (0%)		0/41 (0%)
Nervous system disorders
Subarachnoid haemorrhage	0/41 (0%)		0/40 (0%)		0/41 (0%)		1/41 (2.4%)		0/41 (0%)
VIIth nerve paralysis	0/41 (0%)		0/40 (0%)		0/41 (0%)		1/41 (2.4%)		0/41 (0%)
Other (Not Including Serious) Adverse Events
	Allopurinol 200 mg Treatment Group		RDEA3170 Placebo Treatment Group		RDEA3170 Treatment Group 1		RDEA3170 Treatment Group 2		RDEA3170 Treatment Group 3
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	22/41 (53.7%)		23/40 (57.5%)		26/41 (63.4%)		26/41 (63.4%)		21/41 (51.2%)
Cardiac disorders
Tachycardia	0/41 (0%)		0/40 (0%)		0/41 (0%)		0/41 (0%)		1/41 (2.4%)
Silent myocardial infarction	0/41 (0%)		0/40 (0%)		1/41 (2.4%)		0/41 (0%)		0/41 (0%)
Atrial fibrillation	1/41 (2.4%)		0/40 (0%)		0/41 (0%)		0/41 (0%)		0/41 (0%)
Ear and labyrinth disorders
Tinnitus	0/41 (0%)		1/40 (2.5%)		0/41 (0%)		0/41 (0%)		0/41 (0%)
Vertigo positional	0/41 (0%)		1/40 (2.5%)		0/41 (0%)		0/41 (0%)		0/41 (0%)
Eye disorders
Conjunctivitis	0/41 (0%)		0/40 (0%)		0/41 (0%)		1/41 (2.4%)		0/41 (0%)
Conjunctivitis allergic	0/41 (0%)		0/40 (0%)		0/41 (0%)		0/41 (0%)		1/41 (2.4%)
Dry eye	0/41 (0%)		0/40 (0%)		0/41 (0%)		1/41 (2.4%)		0/41 (0%)
Glaucoma	0/41 (0%)		0/40 (0%)		0/41 (0%)		0/41 (0%)		1/41 (2.4%)
Gastrointestinal disorders
Diarrhoea	1/41 (2.4%)		0/40 (0%)		1/41 (2.4%)		1/41 (2.4%)		2/41 (4.9%)
Constipation	0/41 (0%)		0/40 (0%)		1/41 (2.4%)		2/41 (4.9%)		0/41 (0%)
Abdominal discomfort	0/41 (0%)		0/40 (0%)		1/41 (2.4%)		0/41 (0%)		1/41 (2.4%)
Abdominal pain	0/41 (0%)		0/40 (0%)		1/41 (2.4%)		0/41 (0%)		1/41 (2.4%)
Enterocolitis	0/41 (0%)		0/40 (0%)		0/41 (0%)		1/41 (2.4%)		1/41 (2.4%)
Abdominal pain upper	2/41 (4.9%)		0/40 (0%)		0/41 (0%)		0/41 (0%)		1/41 (2.4%)
Gastritis	0/41 (0%)		2/40 (5%)		1/41 (2.4%)		0/41 (0%)		0/41 (0%)
Gastritis erosive	0/41 (0%)		0/40 (0%)		1/41 (2.4%)		0/41 (0%)		0/41 (0%)
Gastritis haemorrhagic	0/41 (0%)		0/40 (0%)		1/41 (2.4%)		0/41 (0%)		0/41 (0%)
Haemorrhoids	0/41 (0%)		0/40 (0%)		0/41 (0%)		0/41 (0%)		1/41 (2.4%)
Nausea	1/41 (2.4%)		0/40 (0%)		0/41 (0%)		1/41 (2.4%)		0/41 (0%)
Stomatitis	0/41 (0%)		0/40 (0%)		1/41 (2.4%)		0/41 (0%)		0/41 (0%)
Contact stomatitis	0/41 (0%)		0/40 (0%)		0/41 (0%)		0/41 (0%)		1/41 (2.4%)
Chronic gastritis	1/41 (2.4%)		0/40 (0%)		0/41 (0%)		0/41 (0%)		0/41 (0%)
Dyspepsia	0/41 (0%)		1/40 (2.5%)		0/41 (0%)		0/41 (0%)		0/41 (0%)
Gastric polyps	1/41 (2.4%)		0/40 (0%)		0/41 (0%)		0/41 (0%)		0/41 (0%)
General disorders
Fatigue	1/41 (2.4%)		0/40 (0%)		0/41 (0%)		1/41 (2.4%)		0/41 (0%)
Local swelling	0/41 (0%)		0/40 (0%)		0/41 (0%)		1/41 (2.4%)		0/41 (0%)
Oedema peripheral	0/41 (0%)		1/40 (2.5%)		0/41 (0%)		0/41 (0%)		0/41 (0%)
Pyrexia	1/41 (2.4%)		0/40 (0%)		0/41 (0%)		0/41 (0%)		0/41 (0%)
Hepatobiliary disorders
Bile duct stone	1/41 (2.4%)		0/40 (0%)		0/41 (0%)		0/41 (0%)		0/41 (0%)
Cholangitis acute	1/41 (2.4%)		0/40 (0%)		0/41 (0%)		0/41 (0%)		0/41 (0%)
Infections and infestations
Nasopharyngitis	7/41 (17.1%)		7/40 (17.5%)		9/41 (22%)		8/41 (19.5%)		6/41 (14.6%)
Pharyngitis	2/41 (4.9%)		0/40 (0%)		2/41 (4.9%)		1/41 (2.4%)		0/41 (0%)
Bronchitis	1/41 (2.4%)		0/40 (0%)		0/41 (0%)		2/41 (4.9%)		1/41 (2.4%)
Gastroenteritis	1/41 (2.4%)		0/40 (0%)		0/41 (0%)		0/41 (0%)		2/41 (4.9%)
Conjunctivitis viral	0/41 (0%)		0/40 (0%)		1/41 (2.4%)		0/41 (0%)		0/41 (0%)
Gingivitis	0/41 (0%)		0/40 (0%)		0/41 (0%)		1/41 (2.4%)		0/41 (0%)
Influenza	0/41 (0%)		0/40 (0%)		0/41 (0%)		1/41 (2.4%)		0/41 (0%)
Nasal vestibulitis	0/41 (0%)		0/40 (0%)		1/41 (2.4%)		0/41 (0%)		0/41 (0%)
Sinusitis	0/41 (0%)		0/40 (0%)		0/41 (0%)		1/41 (2.4%)		0/41 (0%)
Tonsillitis	1/41 (2.4%)		0/40 (0%)		1/41 (2.4%)		0/41 (0%)		0/41 (0%)
Urethritis	0/41 (0%)		0/40 (0%)		0/41 (0%)		0/41 (0%)		1/41 (2.4%)
Dermatitis infected	1/41 (2.4%)		0/40 (0%)		0/41 (0%)		0/41 (0%)		0/41 (0%)
Herpes virus infection	0/41 (0%)		1/40 (2.5%)		0/41 (0%)		0/41 (0%)		0/41 (0%)
Periodontitis	0/41 (0%)		1/40 (2.5%)		0/41 (0%)		0/41 (0%)		0/41 (0%)
Oral herpes	1/41 (2.4%)		0/40 (0%)		0/41 (0%)		0/41 (0%)		0/41 (0%)
Injury, poisoning and procedural complications
Contusion	1/41 (2.4%)		1/40 (2.5%)		1/41 (2.4%)		0/41 (0%)		1/41 (2.4%)
Ligament sprain	0/41 (0%)		0/40 (0%)		0/41 (0%)		0/41 (0%)		1/41 (2.4%)
Head injury	0/41 (0%)		0/40 (0%)		0/41 (0%)		1/41 (2.4%)		0/41 (0%)
Patella fracture	0/41 (0%)		0/40 (0%)		0/41 (0%)		0/41 (0%)		1/41 (2.4%)
Excoriation	0/41 (0%)		0/40 (0%)		1/41 (2.4%)		0/41 (0%)		0/41 (0%)
Thermal burn	0/41 (0%)		0/40 (0%)		0/41 (0%)		0/41 (0%)		1/41 (2.4%)
Muscle contusion	0/41 (0%)		0/40 (0%)		1/41 (2.4%)		0/41 (0%)		0/41 (0%)
Meniscus injury	0/41 (0%)		0/40 (0%)		1/41 (2.4%)		0/41 (0%)		0/41 (0%)
Fall	0/41 (0%)		1/40 (2.5%)		0/41 (0%)		0/41 (0%)		0/41 (0%)
Hand fracture	1/41 (2.4%)		1/40 (2.5%)		0/41 (0%)		0/41 (0%)		0/41 (0%)
Rib fracture	1/41 (2.4%)		0/40 (0%)		0/41 (0%)		0/41 (0%)		0/41 (0%)
Spinal compression fracture	0/41 (0%)		1/40 (2.5%)		0/41 (0%)		0/41 (0%)		0/41 (0%)
Venomous sting	0/41 (0%)		1/40 (2.5%)		0/41 (0%)		0/41 (0%)		0/41 (0%)
Procedural pain	0/41 (0%)		1/40 (2.5%)		0/41 (0%)		0/41 (0%)		0/41 (0%)
Foreign body	1/41 (2.4%)		0/40 (0%)		0/41 (0%)		0/41 (0%)		0/41 (0%)
Investigations
Blood creatinine increased	0/41 (0%)		0/40 (0%)		2/41 (4.9%)		1/41 (2.4%)		0/41 (0%)
Weight increased	1/41 (2.4%)		0/40 (0%)		0/41 (0%)		0/41 (0%)		0/41 (0%)
Metabolism and nutrition disorders
Dehydration	0/41 (0%)		0/40 (0%)		1/41 (2.4%)		0/41 (0%)		0/41 (0%)
Musculoskeletal and connective tissue disorders
Back pain	1/41 (2.4%)		1/40 (2.5%)		1/41 (2.4%)		4/41 (9.8%)		2/41 (4.9%)
Arthralgia	0/41 (0%)		2/40 (5%)		1/41 (2.4%)		2/41 (4.9%)		1/41 (2.4%)
Periarthritis	1/41 (2.4%)		0/40 (0%)		1/41 (2.4%)		1/41 (2.4%)		1/41 (2.4%)
Pain in extremity	0/41 (0%)		2/40 (5%)		0/41 (0%)		1/41 (2.4%)		1/41 (2.4%)
Arthritis	0/41 (0%)		0/40 (0%)		0/41 (0%)		1/41 (2.4%)		0/41 (0%)
Joint swelling	0/41 (0%)		0/40 (0%)		0/41 (0%)		1/41 (2.4%)		0/41 (0%)
Myalgia	0/41 (0%)		0/40 (0%)		1/41 (2.4%)		0/41 (0%)		0/41 (0%)
Tenosynovitis	0/41 (0%)		0/40 (0%)		0/41 (0%)		1/41 (2.4%)		0/41 (0%)
Intervertebral disc protrusion	1/41 (2.4%)		0/40 (0%)		0/41 (0%)		0/41 (0%)		1/41 (2.4%)
Tendon pain	0/41 (0%)		0/40 (0%)		0/41 (0%)		1/41 (2.4%)		0/41 (0%)
Arthropathy	1/41 (2.4%)		0/40 (0%)		0/41 (0%)		0/41 (0%)		0/41 (0%)
Lumbar spinal stenosis	0/41 (0%)		1/40 (2.5%)		0/41 (0%)		0/41 (0%)		0/41 (0%)
Neck pain	1/41 (2.4%)		0/40 (0%)		0/41 (0%)		0/41 (0%)		0/41 (0%)
Osteoarthritis	0/41 (0%)		2/40 (5%)		0/41 (0%)		0/41 (0%)		0/41 (0%)
Spondylolisthesis	1/41 (2.4%)		0/40 (0%)		0/41 (0%)		0/41 (0%)		0/41 (0%)
Nervous system disorders
Headache	1/41 (2.4%)		0/40 (0%)		1/41 (2.4%)		1/41 (2.4%)		0/41 (0%)
Somnolence	0/41 (0%)		0/40 (0%)		0/41 (0%)		1/41 (2.4%)		0/41 (0%)
Subarachnoid haemorrhage	0/41 (0%)		0/40 (0%)		0/41 (0%)		1/41 (2.4%)		0/41 (0%)
VIIth nerve paralysis	0/41 (0%)		0/40 (0%)		0/41 (0%)		1/41 (2.4%)		0/41 (0%)
Psychiatric disorders
Insomnia	0/41 (0%)		0/40 (0%)		1/41 (2.4%)		1/41 (2.4%)		0/41 (0%)
Depression	0/41 (0%)		0/40 (0%)		0/41 (0%)		0/41 (0%)		1/41 (2.4%)
Renal and urinary disorders
Renal impairment	0/41 (0%)		0/40 (0%)		0/41 (0%)		1/41 (2.4%)		0/41 (0%)
Dysuria	0/41 (0%)		0/40 (0%)		0/41 (0%)		0/41 (0%)		1/41 (2.4%)
Urinary retention	0/41 (0%)		0/40 (0%)		0/41 (0%)		0/41 (0%)		1/41 (2.4%)
Respiratory, thoracic and mediastinal disorders
Upper respiratory tract inflammation	1/41 (2.4%)		2/40 (5%)		1/41 (2.4%)		0/41 (0%)		2/41 (4.9%)
Epistaxis	0/41 (0%)		0/40 (0%)		0/41 (0%)		0/41 (0%)		1/41 (2.4%)
Skin and subcutaneous tissue disorders
Chronic pigmented purpura	0/41 (0%)		1/40 (2.5%)		0/41 (0%)		0/41 (0%)		0/41 (0%)
Rash	0/41 (0%)		0/40 (0%)		1/41 (2.4%)		1/41 (2.4%)		0/41 (0%)
Miliaria	0/41 (0%)		0/40 (0%)		1/41 (2.4%)		0/41 (0%)		0/41 (0%)
Eczema	0/41 (0%)		3/40 (7.5%)		0/41 (0%)		0/41 (0%)		0/41 (0%)
Pruritus	1/41 (2.4%)		0/40 (0%)		0/41 (0%)		0/41 (0%)		0/41 (0%)
Vascular disorders
Hypertension	2/41 (4.9%)		1/40 (2.5%)		1/41 (2.4%)		1/41 (2.4%)		1/41 (2.4%)
Peripheral arterial occlusive disease	0/41 (0%)		0/40 (0%)		1/41 (2.4%)		0/41 (0%)		0/41 (0%)

Limitations/Caveats

[Not Specified]

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Certain Agreements

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

There is NOT 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.