Phase 2 Study of TMX-049 in Subjects With Type 2 Diabetes and Albuminuria

• Sponsor: Teijin America, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03449199
• Collaborator: (none)
• Enrollment: 130
• Locations: 55
• Arms: 3
• Actual Duration (Months): 13.8
• Patients Per Site: 2.4
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

The primary objective of this study is to assess the effect of 2 dose levels of TMX-049 on urinary albumin excretion in subjects with Type 2 diabetes and albuminuria (a urinary albumin-to-creatinine ratio (UACR) 200 to 3000 mg/g and an estimated glomerular filtration rate (eGFR) ≥30 ml/min/1.73m2). Effects of each TMX-049 dose on UACR will be assessed in terms of ratios using log-transformed UACR at Baseline and after a 12-week period of treatment.

Condition or Disease	Intervention/Treatment	Phase
Diabetic Kidney Disease	Drug: TMX-049; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 130 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Randomized, Placebo-Controlled, Double-Blind, Multicenter, Phase 2 Study to Assess Safety, Tolerability, and Renal Effects of TMX-049 in Subjects With Type 2 Diabetes and Albuminuria
• Actual Study Start Date: Apr 10, 2018
• Actual Primary Completion Date: May 7, 2019
• Actual Study Completion Date: Jun 4, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: TMX-049 40 mg QD (Once Daily) TMX-049: 40 mg of TMX-049 to be taken orally, once daily	Drug: TMX-049; A certain dose of TMX-049 to be taken orally, once daily
Experimental: TMX-049 200 mg QD (Once Daily) TMX-049: 200 mg of TMX-049 to be taken orally, once daily	Drug: TMX-049; A certain dose of TMX-049 to be taken orally, once daily
Placebo Comparator: TMX-049 Placebo	Drug: Placebo; Matching placebo to be taken orally, once daily

Outcome Measures

Primary Outcome Measures

1. Changes in Log-transformed Urinary Albumin-to-creatinine Ratio (UACR) at Week 12 [Baseline and Week 12]

   UACR from Baseline to Weeks 2, 6, 12, and 16(Follow-up) were measured. The change from baseline at Week 12 in log-transformed UACR was analyzed.

Secondary Outcome Measures

1. Changes in Estimated Glomerular Filtration Rate (GFR) [Baseline and Week 2, 6, 12, 16 (Follow-up)]

   Estimated Glomerular Filtration Rate from Baseline to Weeks 2, 6, 12/early termination, and 16 (Follow-up) were measured. The eGFR (estimated glomerular filtration rate) was calculated using the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) formula based on the serum creatinine measurement.

2. Changes in Serum Uric Acid (sUA) [Baseline and Week 2, 6, 12, 16 (Follow-up)]

   Serum Uric Acid from Baseline to Weeks 2, 6, 12/early termination, and 16 (Follow-up) were measured in order to explore the sUA (Serum Uric Acid) lowering effect in DKD (diabetic kidney disease) patients and the relationship between sUA and efficacy to DKD.

3. Changes in Urinary Albumin-to-Creatinine Ratio (UACR) [Baseline and Week 2, 6, 12, 16 (Follow-up)]

   Urinary Albumin-to-Creatinine Ratio from Baseline to Weeks 2, 6, 12/early termination, and 16 (Follow-up) were measured.

4. Proportion of Subjects With a Greater Than 30% Reduction From Baseline to Week 12 in Urinary Albumin-to-Creatinine Ratio [16 Weeks]

   Changes in Proportion of Subjects With a Greater Than 30% Reduction From Baseline to Week 12 in Urinary Albumin-to-Creatinine Ratio were measured. Subject with greater than 30% reduction is estimated as responder, less than or equal to 30% reduction is estimated as non-responder.

5. Changes in Exploratory Blood Biomarkers (C Reactive Protein) [16 Weeks]

   Changes in Exploratory Blood Biomarkers for inflammation (C Reactive Protein) from Baseline to Weeks 2, 6, 12/early termination, and 16 (Follow-up) were measured.

6. Changes in Exploratory Blood Biomarkers (Soluble TNF Receptor Type I) [16 Weeks]

   Changes in Exploratory Blood Biomarkers for inflammation (Soluble TNF [tumor necrosis factor] Receptor Type I) from Baseline to Weeks 2, 6, 12/early termination, and 16 (Follow-up) were measured.

7. Changes in Exploratory Renal Biomarkers (Creatinine-Corrected Fatty Acid Binding Protein 1) [16 Weeks]

   Changes in Exploratory Renal Biomarkers for renal tubular diseases (Creatinine-Corrected Fatty Acid Binding Protein 1) from Baseline to Weeks 2, 6, 12/early termination, and 16 (Follow-up) were measured.

8. Changes in Exploratory Renal Biomarkers (Creatinine-Corrected Hydroxy Deoxyguanosine) [16 Weeks]

   Changes in Exploratory Renal Biomarkers for renal tubular diseases (Creatinine-Corrected Hydroxy Deoxyguanosine) from Baseline to Weeks 2, 6, 12/early termination, and 16 (Follow-up) were measured.

9. Changes in Exploratory Renal Biomarkers (Creatinine-Corrected Kidney Injury Molecule-1) [16 Weeks]

   Changes in Exploratory Renal Biomarkers for renal tubular diseases (Creatinine-Corrected Kidney Injury Molecule-1) from Baseline to Weeks 2, 6, 12/early termination, and 16 (Follow-up) were measured.

10. Changes in Exploratory Renal Biomarkers (Creatinine-Corrected N-acetyl-beta-D-glucosaminidase) [16 Weeks]

    Changes in Exploratory Renal Biomarkers for renal tubular diseases (Creatinine-Corrected N-acetyl-beta-D-glucosaminidase) from Baseline to Weeks 2, 6, 12/early termination, and 16 (Follow-up) were measured.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Type 2 diabetes treated with ≥1 glucose-lowering medication for at least 12 months

• UACR 200 to 3000 mg/g

• eGFR ≥30 ml/min/1.73m2

• Treated with at least the minimal recommended dose of an angiotensin converting enzyme inhibitor (ACEI) or an angiotensin II receptor blocker (ARB), but not both

Exclusion Criteria:

• History of Type 1 diabetes

• Women who are breast feeding

• Treatment with any uric acid-lowering therapy within previous 2 weeks

• History of intolerance to any XO (xanthine oxidase) inhibitor

• History of a gout flare requiring pharmacologic treatment

• History or presence of tophaceous gout

• History of immunosuppressant treatment for any known or suspected renal disorder

• History of a non-diabetic form of renal disease

• Glycosylated hemoglobin (HbA1c) >11%

• sUA <4.0 mg/dL or >10.0 mg/dL

• Positive urinary pregnancy test

• Dialysis for acute renal failure within previous 6 months

• Renal allograft in place or a scheduled kidney transplant within the next 22 weeks

• Congenital or acquired solitary kidney

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	AKDHC Medical Research Services, LLC	Flagstaff	Arizona	United States	86001
2	Aventiv Research Inc.	Mesa	Arizona	United States	85210
3	Comprehensive Research Institute	Alhambra	California	United States	91801
4	California Kidney Specialists	Covina	California	United States	91723
5	Torrance Clinical Research Institute, Inc.	Lomita	California	United States	90717
6	Valley Clinical Trials, Inc.	Northridge	California	United States	91325
7	Diabetes Associates Medical Group	Orange	California	United States	92868
8	Desert Oasis Healthcare Medical Group	Palm Springs	California	United States	92262
9	California Kidney Specialists	San Dimas	California	United States	91773
10	North America Research Institute	San Dimas	California	United States	91773
11	San Marcus Research Clinic, Inc.	Miami Lakes	Florida	United States	33014
12	Leon Medical Research	Miami	Florida	United States	33015
13	Endocrine Associates of Florida, P.A.	Ocoee	Florida	United States	34761
14	Pines Care Research Center	Pembroke Pines	Florida	United States	33026
15	Hanson Clinical Research Center	Port Charlotte	Florida	United States	33952
16	Nephrology Associates, PC	Augusta	Georgia	United States	30901
17	Southeastern Clinical Research Institute	Augusta	Georgia	United States	30909
18	East-West Medical Research Institute	Honolulu	Hawaii	United States	96814
19	Solaris Clinical Research, Llc	Meridian	Idaho	United States	83646
20	Associate in Endocrinology	Elgin	Illinois	United States	60124
21	Community Clinical Research Center	Anderson	Indiana	United States	46011
22	Community Hospital of Anderson and Madison County, Inc.	Anderson	Indiana	United States	46011
23	Iowa Kidney Physicians	Des Moines	Iowa	United States	50265
24	Iowa Diabetes and Endocrinology Research Center	West Des Moines	Iowa	United States	50265
25	My Kidney Center, LLC.	Manhattan	Kansas	United States	66502
26	Cotton O'Neil Clinical Research Center	Topeka	Kansas	United States	66606
27	Four Rivers Clincial Research	Paducah	Kentucky	United States	42003
28	Ochsner Clinic Foundation, Baton Rouge	Baton Rouge	Louisiana	United States	70809
29	Biolab Research LLC	Rockville	Maryland	United States	20852
30	Aa Mrc Llc	Flint	Michigan	United States	48504
31	Elite Research Center LLC	Flint	Michigan	United States	48532
32	Endocrine Consultants of Mid Michigan	Flint	Michigan	United States	48532
33	Seacost Kidney & Hypertension Specialists	Portsmouth	New Hampshire	United States	03801
34	Albany Medical College, Division of Community Endocinology	Albany	New York	United States	12206
35	Randolph Health Internal Medicine	Asheboro	North Carolina	United States	27203
36	Carteret Medical Group	Morehead City	North Carolina	United States	28557
37	PMG Research of Wilmington, LLC	Wilmington	North Carolina	United States	28401
38	Brookview Hills Research Associates, LLC	Winston-Salem	North Carolina	United States	27103
39	Synexus Clinical Research US, Inc. Centennial Health, PC	Oklahoma City	Oklahoma	United States	73111
40	Detweiler Family Medicine & Associates, PC	Lansdale	Pennsylvania	United States	19446
41	University Diabetes & Endocrine Consultants	Chattanooga	Tennessee	United States	37411
42	Knoxville Kidney Center, PLLC	Knoxville	Tennessee	United States	37923
43	Texas Health Physicians Group	Dallas	Texas	United States	75243
44	The Medical Group of Texas	Fort Worth	Texas	United States	76116
45	Rockwood Medical Clinic	Fort Worth	Texas	United States	76164
46	Endocrine Associates	Houston	Texas	United States	77004
47	Juno Research, LLC	Houston	Texas	United States	77040
48	The Endocrine Center	Houston	Texas	United States	77079
49	Pioneer Research Solutions INC	Houston	Texas	United States	77099
50	Houston Nephrology Research	Houston	Texas	United States	77429
51	Clinical Advancement Center, PLLC	San Antonio	Texas	United States	78212
52	BFHC Research	San Antonio	Texas	United States	78249
53	Carl R. Meisner Medical Clinic, PLLC	Sugar Land	Texas	United States	77478
54	University of Utah School of Medicine	Salt Lake City	Utah	United States	84108
55	Manassas Clinical Research Center	Manassas	Virginia	United States	20110

Sponsors and Collaborators

• Teijin America, Inc.

Investigators

• Study Director: Michael Cressman, D.O., Covance

Study Documents (Full-Text)

• Study Protocol - Feb 7, 2018
• Statistical Analysis Plan - Apr 12, 2019

More Information

Publications

None provided.

• Responsible Party: Teijin America, Inc.
• ClinicalTrials.gov Identifier: NCT03449199
• Other Study ID Numbers: TMX-049DN-201
• First Posted: Feb 28, 2018
• Last Update Posted: Aug 1, 2022
• Last Verified: Jul 1, 2022

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Teijin America, Inc.: Diabetic Kidney Disease; XO inhibitor; UACR
• Additional relevant MeSH terms: Kidney Diseases; Albuminuria; Diabetic Nephropathies

Study Results

Participant Flow

Arm/Group Title	TMX-049 Placebo	TMX-049 40mg QD	TMX-049 200mg QD
Arm/Group Description	Placebo: Matching placebo to be taken orally, once daily	TMX-049: 40mg of TMX-049 to be taken orally, once daily	TMX-049: 200 mg of TMX-049 to be taken orally, once daily
Period Title: Overall Study
STARTED	42	44	44
COMPLETED	41	43	42
NOT COMPLETED	1	1	2

Baseline Characteristics

Arm/Group Title	TMX-049 Placebo	TMX-049 40 mg QD	TMX-049 200 mg QD	Total
Arm/Group Description	Placebo: Matching placebo to be taken orally, once daily	TMX-049: 40 mg of TMX-049 to be taken orally, once daily	TMX-049: 200 mg of TMX-049 to be taken orally, once daily	Total of all reporting groups
Overall Participants	42	43	44	129
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	65 (10.3)	66 (10.7)	68 (10)	66 (10.3)
Sex: Female, Male (Count of Participants)
Female	18 42.9%	17 39.5%	18 40.9%	53 41.1%
Male	24 57.1%	26 60.5%	26 59.1%	76 58.9%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	1 2.3%	0 0%	1 0.8%
Asian	4 9.5%	2 4.7%	1 2.3%	7 5.4%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%
Black or African American	5 11.9%	2 4.7%	8 18.2%	15 11.6%
White	32 76.2%	38 88.4%	35 79.5%	105 81.4%
More than one race	1 2.4%	0 0%	0 0%	1 0.8%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%
Weight (kg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg]	90.1 (19.81)	95.9 (20.58)	98.8 (23.63)	95.0 (21.57)
BMI (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	31.6 (6.00)	33.6 (6.57)	34.3 (7.26)	32.2 (6.69)

Outcome Measures

1. Primary Outcome

Title	Changes in Log-transformed Urinary Albumin-to-creatinine Ratio (UACR) at Week 12
Description	UACR from Baseline to Weeks 2, 6, 12, and 16(Follow-up) were measured. The change from baseline at Week 12 in log-transformed UACR was analyzed.
Time Frame	Baseline and Week 12

Outcome Measure Data

Analysis Population Description

Modified Intention-to-Treat (mITT) Population consisted of all randomized subjects who had at least 1 post-randomization UACR assessment. Subjects in the mITT Population were analyzed according to their randomized treatment.

Arm/Group Title	TMX-049 Placebo	TMX-049 40 mg QD	TMX-049 200 mg QD
Arm/Group Description	Placebo: Matching placebo to be taken orally, once daily, for 12 weeks	TMX-049: 40 mg of TMX-049 to be taken orally, once daily for 12 weeks	TMX-049: 200 mg of TMX-049 to be taken orally, once daily for 12 weeks
Measure Participants	42	43	44
Least Squares Mean (Standard Error) [Log(mg/g)]	-0.10 (0.153)	-0.15 (0.151)	-0.53 (0.150)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	TMX-049 Placebo, TMX-049 40 mg QD
	Comments	Change from baseline in log-transformed UACR was analyzed using an ANCOVA model with randomized treatment, and randomization strata of sUA and UACR as independent variables. The last observation carried forward imputation was used for missing data. In this study, multiplicity was not considered since the study objective is exploratory.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.7953
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.05
	Confidence Interval	(2-Sided) 95%; -0.44 to 0.34
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	TMX-049 Placebo, TMX-049 200 mg QD
	Comments	Change from baseline in log-transformed UACR was analyzed using an ANCOVA model with randomized treatment, and randomization strata of sUA and UACR as independent variables. The last observation carried forward imputation was used for missing data. In this study, multiplicity was not considered since the study objective is exploratory.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0311
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.43
	Confidence Interval	(2-Sided) 95%; -0.82 to -0.04
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Changes in Estimated Glomerular Filtration Rate (GFR)
Description	Estimated Glomerular Filtration Rate from Baseline to Weeks 2, 6, 12/early termination, and 16 (Follow-up) were measured. The eGFR (estimated glomerular filtration rate) was calculated using the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) formula based on the serum creatinine measurement.
Time Frame	Baseline and Week 2, 6, 12, 16 (Follow-up)

Outcome Measure Data

Analysis Population Description

Modified Intention-to-Treat (mITT) Population consisted of all randomized subjects who had at least 1 post-randomization UACR assessment. Subjects in the mITT Population were analyzed according to their randomized treatment.

Arm/Group Title	TMX-049 Placebo	TMX-049 40 mg QD	TMX-049 200 mg QD
Arm/Group Description	Placebo: Matching placebo to be taken orally, once daily for 12 weeks	TMX-049:40 mg of TMX-049 to be taken orally, once daily for 12 weeks	TMX-049: 200 mg of TMX-049 to be taken orally, once daily for 12 weeks
Measure Participants	42	43	44
Visit 4 (Week 2)	-0.02 (1.591)	0.98 (1.601)	0.18 (1.561)
Visit 5 (Week 6)	-1.41 (1.757)	-1.06 (1.732)	0.00 (1.724)
Visit 6/ET (Week 12)	-2.34 (1.585)	-0.62 (1.563)	1.09 (1.556)
Visit 7/Follow up (Week 16)	-2.39 (1.726)	1.57 (1.702)	0.99 (1.695)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	TMX-049 Placebo, TMX-049 40 mg QD
	Comments	For Week 12 (visit of the primary outcome), ANCOVA model with treatment, randomization strata of sUA and UACR levels as independent variables, Baseline eGFR as covariate is fitted. The last observation carried forward imputation was used for missing data.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.4055
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	1.71
	Confidence Interval	(2-Sided) 95%; -2.35 to 5.78
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	TMX-049 Placebo, TMX-049 200 mg QD
	Comments	For Week 12 (visit of the primary outcome), an ANCOVA model with treatment, randomization strata of sUA and UACR levels as independent variables, Baseline eGFR as covariate is fitted. The last observation carried forward imputation was used for missing data.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0960
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	3.42
	Confidence Interval	(2-Sided) 95%; -0.62 to 7.46
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Changes in Serum Uric Acid (sUA)
Description	Serum Uric Acid from Baseline to Weeks 2, 6, 12/early termination, and 16 (Follow-up) were measured in order to explore the sUA (Serum Uric Acid) lowering effect in DKD (diabetic kidney disease) patients and the relationship between sUA and efficacy to DKD.
Time Frame	Baseline and Week 2, 6, 12, 16 (Follow-up)

Outcome Measure Data

Analysis Population Description

Modified Intention-to-Treat (mITT) Population consisted of all randomized subjects who had at least 1 post-randomization UACR assessment. Subjects in the mITT Population were analyzed according to their randomized treatment

Arm/Group Title	TMX-049 Placebo	TMX-049 40 mg QD	TMX-049 200 mg QD
Arm/Group Description	Placebo: Matching placebo to be taken orally, once daily for 12 weeks	TMX-049: 40 mg of TMX-049 to be taken orally, once daily for 12 weeks	TMX-049: 200 mg of TMX-049 to be taken orally, once daily for 12 weeks
Measure Participants	42	43	44
Visit 4 (Week 2)	-0.03 (0.238)	-2.57 (0.240)	-3.54 (0.234)
Visit 5 (Week 6)	-0.22 (0.256)	-2.54 (0.252)	-3.34 (0.251)
Visit 6/ET (Week 12)	-0.07 (0.269)	-2.51 (0.266)	-3.30 (0.265)
Visit 7/Follow up (Week 16)	0.21 (0.190)	-0.13 (0.188)	-0.33 (0.187)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	TMX-049 Placebo, TMX-049 40 mg QD
	Comments	For Week 12 (visit of the primary outcome), an ANCOVA model with treatment, randomization strata of UACR levels as independent variables is fitted. The last observation carried forward imputation was used for missing data.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-2.43
	Confidence Interval	(2-Sided) 95%; -3.13 to -1.74
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	TMX-049 Placebo, TMX-049 200 mg QD
	Comments	For Week 12 (visit of the primary outcome), an ANCOVA model with treatment, randomization strata of UACR levels as independent variables is fitted. The last observation carried forward imputation was used for missing data.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-3.23
	Confidence Interval	(2-Sided) 95%; -3.91 to -2.54
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Changes in Urinary Albumin-to-Creatinine Ratio (UACR)
Description	Urinary Albumin-to-Creatinine Ratio from Baseline to Weeks 2, 6, 12/early termination, and 16 (Follow-up) were measured.
Time Frame	Baseline and Week 2, 6, 12, 16 (Follow-up)

Outcome Measure Data

Analysis Population Description

Modified Intention-to-Treat (mITT) Population consisted of all randomized subjects who had at least 1 post-randomization UACR assessment. Subjects in the mITT Population were analyzed according to their randomized treatment

Arm/Group Title	TMX-049 Placebo	TMX-049 40 mg QD	TMX-049 200 mg QD
Arm/Group Description	Placebo: Matching placebo to be taken orally, once daily for 12 weeks	TMX-049: 40 mg of TMX-049 to be taken orally, once daily for 12 weeks	TMX-049: 200 mg of TMX-049 to be taken orally, once daily for 12 weeks
Measure Participants	42	43	44
Visit 4 (Week 2)	25.44 (69.166)	53.88 (68.229)	-86.20 (67.932)
Visit 5 (Week 6)	-81.90 (68.156)	-30.37 (67.233)	-86.12 (66.940)
Visit 6/ET (Week 12)	61.92 (92.291)	-40.10 (91.041)	-135.57 (90.645)
Visit 7/ Follow up (Week 16)	72.07 (90.045)	58.31 (88.825)	-8.27 (88.439)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	TMX-049 Placebo, TMX-049 40 mg QD
	Comments	For Week 12 (visit of the primary outcome), an ANCOVA model with treatment, randomization strata of UACR levels as independent variables is fitted. The last observation carried forward imputation was used for missing data.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.3955
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-102.02
	Confidence Interval	(2-Sided) 95%; -338.81 to 134.78
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	TMX-049 Placebo, TMX-049 200 mg QD
	Comments	For Week 12 (visit of the primary outcome), ANCOVA model with treatment, randomization strata of UACR levels as independent variables is fitted. The last observation carried forward imputation was used for missing data.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0991
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-197.49
	Confidence Interval	(2-Sided) 95%; -432.73 to 37.75
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

Title	Proportion of Subjects With a Greater Than 30% Reduction From Baseline to Week 12 in Urinary Albumin-to-Creatinine Ratio
Description	Changes in Proportion of Subjects With a Greater Than 30% Reduction From Baseline to Week 12 in Urinary Albumin-to-Creatinine Ratio were measured. Subject with greater than 30% reduction is estimated as responder, less than or equal to 30% reduction is estimated as non-responder.
Time Frame	16 Weeks

Outcome Measure Data

Analysis Population Description

Modified Intention-to-Treat (mITT) Population consisted of all randomized subjects who had at least 1 post-randomization UACR assessment. Subjects in the mITT Population were analyzed according to their randomized treatment.

Arm/Group Title	TMX-049 Placebo	TMX-049 40 mg QD	TMX-049 200 mg QD
Arm/Group Description	Placebo: Matching placebo to be taken orally, once daily for 12 weeks	TMX-049: 40 mg of TMX-049 to be taken orally, once daily for 12 weeks	TMX-049: 200 mg of TMX-049 to be taken orally, once daily for 12 weeks
Measure Participants	42	43	44
Responder	10 23.8%	14 32.6%	19 43.2%
Non-responder	32 76.2%	29 67.4%	25 56.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	TMX-049 Placebo
	Comments	Odds ratio, 95% CLs, and p-values are obtained from logistic regression model adjusting for treatment group, randomization strata of Baseline sUA (<6.0 vs ≥6.0 mg/dL) and Baseline UACR (200 to <300 mg/g vs 300 to ≤3000 mg/g), Baseline UACR and Baseline sUA levels. Odds ratio for a baseline covariate is the ratio of odds over one unit increase of the covariate and it is assumed constant. P-value represents the statistical significance level of odds ratio differing from 1.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.2791
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.72
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments	Missing observations at Study Week 12 are imputed as nonresponse.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	TMX-049 Placebo, TMX-049 200 mg QD
	Comments	Odds ratio, 95% CLs, and p-values are obtained from logistic regression model adjusting for treatment group, randomization strata of Baseline sUA (<6.0 vs ≥6.0 mg/dL) and Baseline UACR (200 to <300 mg/g vs 300 to ≤3000 mg/g), Baseline UACR and Baseline sUA levels. Odds ratio for a baseline covariate is the ratio of odds over one unit increase of the covariate and it is assumed constant. P-value represents the statistical significance level of odds ratio differing from 1.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0507
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	2.57
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

6. Secondary Outcome

Title	Changes in Exploratory Blood Biomarkers (C Reactive Protein)
Description	Changes in Exploratory Blood Biomarkers for inflammation (C Reactive Protein) from Baseline to Weeks 2, 6, 12/early termination, and 16 (Follow-up) were measured.
Time Frame	16 Weeks

Outcome Measure Data

Analysis Population Description

Safety Population consisted of all randomized subjects who received at least one study drug tablet or capsule. Subjects were analyzed according to the actual treatment received.

Arm/Group Title	TMX-049 Placebo	TMX-049 40 mg QD	TMX-049 200 mg QD
Arm/Group Description	Placebo: Matching placebo to be taken orally, once daily for 12 weeks	TMX-049: 40 mg of TMX-049 to be taken orally, once daily for 12 weeks	TMX-049: 200 mg of TMX-049 to be taken orally, once daily for 12 weeks
Measure Participants	42	44	44
Visit 4 (Week 2)	0.046 (0.5168)	0.014 (0.5384)	0.087 (0.6194)
Visit 5 (Week 6)	-0.011 (0.6443)	0.003 (0.3688)	-0.084 (0.4303)
Visit 6/ET (Week 12)	0.000 (0.7527)	-0.144 (0.3691)	0.000 (0.5176)
Visit 7/ Follow up (Week 16)	0.012 (0.6507)	-0.084 (0.3606)	-0.046 (0.3917)

7. Secondary Outcome

Title	Changes in Exploratory Blood Biomarkers (Soluble TNF Receptor Type I)
Description	Changes in Exploratory Blood Biomarkers for inflammation (Soluble TNF [tumor necrosis factor] Receptor Type I) from Baseline to Weeks 2, 6, 12/early termination, and 16 (Follow-up) were measured.
Time Frame	16 Weeks

Outcome Measure Data

Analysis Population Description

Safety Population consisted of all randomized subjects who received at least one study drug tablet or capsule. Subjects were analyzed according to the actual treatment received.

Arm/Group Title	for 12 weeksTMX-049 Placebo	TMX-049 40 mg QD	TMX-049 200 mg QD
Arm/Group Description	Placebo: Matching placebo to be taken orally, once daily for 12 weeks	TMX-049: 40 mg of TMX-049 to be taken orally, once daily for 12 weeks	TMX-049: 200 mg of TMX-049 to be taken orally, once daily for 12 weeks
Measure Participants	42	44	44
Visit 4 (Week 2)	-13.7 (367.11)	-92.3 (298.83)	38.7 (360.03)
Visit 5 (Week 6)	-77.1 (295.50)	47.6 (485.92)	60.7 (397.76)
Visit 6 (Week 12)	16.5 (371.88)	10.8 (455.11)	43.8 (265.35)
Visit 7/Follow up (Week 16)	-25.8 (366.94)	-36.3 (308.79)	13.8 (320.22)

8. Secondary Outcome

Title	Changes in Exploratory Renal Biomarkers (Creatinine-Corrected Fatty Acid Binding Protein 1)
Description	Changes in Exploratory Renal Biomarkers for renal tubular diseases (Creatinine-Corrected Fatty Acid Binding Protein 1) from Baseline to Weeks 2, 6, 12/early termination, and 16 (Follow-up) were measured.
Time Frame	16 Weeks

Outcome Measure Data

Analysis Population Description

Safety Population consisted of all randomized subjects who received at least one study drug tablet or capsule. Subjects were analyzed according to the actual treatment received.

Arm/Group Title	TMX-049 Placebo	TMX-049 40 mg QD	TMX-049 200 mg QD
Arm/Group Description	Placebo: Matching placebo to be taken orally, once daily for 12 weeks	TMX-049: 40 mg of TMX-049 to be taken orally, once daily for 12 weeks	TMX-049: 200 mg of TMX-049 to be taken orally, once daily for 12 weeks
Measure Participants	42	44	44
Visit 4 (Week 2)	0.03 (0.161)	0.01 (0.214)	-0.04 (0.201)
Visit 5 (Week 6)	-0.04 (0.309)	0.04 (0.258)	-0.04 (0.201)
Visit 6 (Week 12)	-0.01 (0.317)	-0.01 (0.136)	-0.01 (0.218)
Visit 7/Follow up (Week 16)	0.02 (0.321)	0.04 (0.289)	0.00 (0.188)

9. Secondary Outcome

Title	Changes in Exploratory Renal Biomarkers (Creatinine-Corrected Hydroxy Deoxyguanosine)
Description	Changes in Exploratory Renal Biomarkers for renal tubular diseases (Creatinine-Corrected Hydroxy Deoxyguanosine) from Baseline to Weeks 2, 6, 12/early termination, and 16 (Follow-up) were measured.
Time Frame	16 Weeks

Outcome Measure Data

Analysis Population Description

Safety Population consisted of all randomized subjects who received at least one study drug tablet or capsule. Subjects were analyzed according to the actual treatment received.

Arm/Group Title	TMX-049 Placebo	TMX-049 40 mg QD	TMX-049 200 mg QD
Arm/Group Description	Placebo: Matching placebo to be taken orally, once daily for 12 weeks	TMX-049: 40 mg of TMX-049 to be taken orally, once daily for 12 weeks	TMX-049: 200 mg of TMX-049 to be taken orally, once daily for 12 weeks
Measure Participants	42	44	44
Visit 4 (Week 2)	1.47 (4.266)	4.70 (4.123)	6.08 (5.809)
Visit 5 (Week 6)	1.72 (5.179)	3.22 (5.321)	4.88 (5.930)
Visit 6 (Week 12)	-1.86 (5.372)	3.75 (6.157)	6.87 (10.476)
Visit 7/ Follow up (Week 16)	1.20 (5.480)	-0.07 (5.647)	-3.14 (5.211)

10. Secondary Outcome

Title	Changes in Exploratory Renal Biomarkers (Creatinine-Corrected Kidney Injury Molecule-1)
Description	Changes in Exploratory Renal Biomarkers for renal tubular diseases (Creatinine-Corrected Kidney Injury Molecule-1) from Baseline to Weeks 2, 6, 12/early termination, and 16 (Follow-up) were measured.
Time Frame	16 Weeks

Outcome Measure Data

Analysis Population Description

Safety Population consisted of all randomized subjects who received at least one study drug tablet or capsule. Subjects were analyzed according to the actual treatment received.

Arm/Group Title	TMX-049 Placebo	TMX-049 40 mg QD	TMX-049 200 mg QD
Arm/Group Description	Placebo: Matching placebo to be taken orally, once daily for 12 weeks	TMX-049: 40 mg of TMX-049 to be taken orally, once daily for 12 weeks	TMX-049: 200 mg of TMX-049 to be taken orally, once daily for 12 weeks
Measure Participants	42	44	44
Visit 4 (Week 2)	0.00 (0.010)	0.00 (0.016)	0.00 (0.007)
Visit 5 (Week 6)	0.00 (0.010)	0.00 (0.015)	0.00 (0.006)
Visit 6 (Week 12)	0.00 (0.019)	0.00 (0.015)	0.00 (0.008)
Visit 7/Follow up (Week 16)	0.00 (0.009)	0.00 (0.0014)	0.00 (0.009)

11. Secondary Outcome

Title	Changes in Exploratory Renal Biomarkers (Creatinine-Corrected N-acetyl-beta-D-glucosaminidase)
Description	Changes in Exploratory Renal Biomarkers for renal tubular diseases (Creatinine-Corrected N-acetyl-beta-D-glucosaminidase) from Baseline to Weeks 2, 6, 12/early termination, and 16 (Follow-up) were measured.
Time Frame	16 Weeks

Outcome Measure Data

Analysis Population Description

Safety Population consisted of all randomized subjects who received at least one study drug tablet or capsule. Subjects were analyzed according to the actual treatment received.

Arm/Group Title	TMX-049 Placebo	TMX-049 40 mg QD	TMX-049 200 mg QD
Arm/Group Description	Placebo: Matching placebo to be taken orally, once daily for 12 weeks	TMX-049: 40 mg of TMX-049 to be taken orally, once daily for 12 weeks	TMX-049: 200 mg of TMX-049 to be taken orally, once daily for 12 weeks
Measure Participants	42	44	44
Visit 4 (Week 2)	-0.01 (0.129)	0.03 (0.136)	-0.01 (0.152)
Visit 5 (Week 6)	0.02 (0.154)	0.02 (0.121)	-0.02 (0.147)
Visit 6 (Week 12)	0.00 (0.123)	0.02 (0.143)	-0.02 (0.108)
Visit 7/Follow up (Week 16)	0.01 (0.089)	0.02 (0.116)	-0.01 (0.132)

Adverse Events

Time Frame	Adverse event (AE) reporting began from the time of informed consent and ends at the Follow-up Visit (Visit 7), up to 16 weeks. For subjects without the Follow-up Visit, the reporting ends 28 days after the last dose of the Investigational Medicinal Product, up to 12 weeks.
Adverse Event Reporting Description	Treatment-emergent AEs (TEAEs) were defined as any events with start date on or after the date of first dose of double-blind study drug and up to 30 days after date of last dose of double-blind study drug.
Arm/Group Title	TMX-049 Placebo		TMX-049 40 mg QD		TMX-049: 200 mg
Arm/Group Description	Placebo: Matching placebo to be taken orally, once daily		TMX-049: 40 mg of TMX-049 to be taken orally, once daily		TMX-049: 200 mg of TMX-049 to be taken orally, once daily
All Cause Mortality
	TMX-049 Placebo		TMX-049 40 mg QD		TMX-049: 200 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/42 (0%)		0/44 (0%)		0/44 (0%)
Serious Adverse Events
	TMX-049 Placebo		TMX-049 40 mg QD		TMX-049: 200 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/42 (9.5%)		4/44 (9.1%)		2/44 (4.5%)
Cardiac disorders
Cardiac failure chronic	1/42 (2.4%)		0/44 (0%)		0/44 (0%)
Gastrointestinal disorders
Pancreatitis acute	0/42 (0%)		1/44 (2.3%)		0/44 (0%)
Infections and infestations
Cholecystitis infective	1/42 (2.4%)		0/44 (0%)		0/44 (0%)
Pneumonia	1/42 (2.4%)		0/44 (0%)		0/44 (0%)
Sepsis	0/42 (0%)		1/44 (2.3%)		0/44 (0%)
Metabolism and nutrition disorders
Hypoglycaemia	0/42 (0%)		1/44 (2.3%)		0/44 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Myelodysplastic syndrome	0/42 (0%)		1/44 (2.3%)		0/44 (0%)
Nervous system disorders
Loss of consciousness	0/42 (0%)		0/44 (0%)		1/44 (2.3%)
Lumbar radiculopathy	1/42 (2.4%)		0/44 (0%)		0/44 (0%)
Renal and urinary disorders
Acute kidney injury	1/42 (2.4%)		1/44 (2.3%)		0/44 (0%)
Respiratory, thoracic and mediastinal disorders
Asthma	1/42 (2.4%)		0/44 (0%)		0/44 (0%)
Chronic obstructive pulmonary disease	0/42 (0%)		0/44 (0%)		1/44 (2.3%)
Respiratory failure	1/42 (2.4%)		0/44 (0%)		0/44 (0%)
Other (Not Including Serious) Adverse Events
	TMX-049 Placebo		TMX-049 40 mg QD		TMX-049: 200 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	18/42 (42.9%)		19/44 (43.2%)		17/44 (38.6%)
Blood and lymphatic system disorders
Anaemia	1/42 (2.4%)		1/44 (2.3%)		0/44 (0%)
Reticulocytosis	0/42 (0%)		1/44 (2.3%)		0/44 (0%)
Cardiac disorders
Bundle branch block right	0/42 (0%)		0/44 (0%)		1/44 (2.3%)
Palpitations	1/42 (2.4%)		0/44 (0%)		0/44 (0%)
Ear and labyrinth disorders
Middle ear disorder	0/42 (0%)		0/44 (0%)		1/44 (2.3%)
Endocrine disorders
Hypothyroidism	0/42 (0%)		2/44 (4.5%)		0/44 (0%)
Gastrointestinal disorders
Abdominal pain	0/42 (0%)		1/44 (2.3%)		1/44 (2.3%)
Abdominal pain lower	1/42 (2.4%)		0/44 (0%)		0/44 (0%)
Constipation	1/42 (2.4%)		1/44 (2.3%)		0/44 (0%)
Diarrhoea	2/42 (4.8%)		0/44 (0%)		3/44 (6.8%)
Dyspepsia	0/42 (0%)		1/44 (2.3%)		0/44 (0%)
Haematemesis	0/42 (0%)		1/44 (2.3%)		0/44 (0%)
Nausea	0/42 (0%)		3/44 (6.8%)		3/44 (6.8%)
Oesophageal pain	0/42 (0%)		0/44 (0%)		1/44 (2.3%)
Vomiting	1/42 (2.4%)		1/44 (2.3%)		1/44 (2.3%)
General disorders
Chest pain	1/42 (2.4%)		0/44 (0%)		0/44 (0%)
Drug interaction	0/42 (0%)		1/44 (2.3%)		0/44 (0%)
Oedema	1/42 (2.4%)		2/44 (4.5%)		0/44 (0%)
Oedema peripheral	1/42 (2.4%)		3/44 (6.8%)		0/44 (0%)
Pyrexia	0/42 (0%)		1/44 (2.3%)		0/44 (0%)
Immune system disorders
Drug hypersensitivity	0/42 (0%)		0/44 (0%)		1/44 (2.3%)
Infections and infestations
Cellulitis	0/42 (0%)		1/44 (2.3%)		0/44 (0%)
Gastroenteritis	0/42 (0%)		1/44 (2.3%)		0/44 (0%)
Influenza	0/42 (0%)		2/44 (4.5%)		0/44 (0%)
Lower respiratory tract infection	1/42 (2.4%)		0/44 (0%)		0/44 (0%)
Nasopharyngitis	3/42 (7.1%)		0/44 (0%)		1/44 (2.3%)
Sinusitis	1/42 (2.4%)		1/44 (2.3%)		0/44 (0%)
Subcutaneous abscess	0/42 (0%)		1/44 (2.3%)		0/44 (0%)
Upper respiratory tract infection	0/42 (0%)		2/44 (4.5%)		0/44 (0%)
Urinary tract infection	3/42 (7.1%)		1/44 (2.3%)		1/44 (2.3%)
Urinary tract infection bacterial	0/42 (0%)		0/44 (0%)		1/44 (2.3%)
Viral infection	1/42 (2.4%)		0/44 (0%)		0/44 (0%)
Abscess limb	0/42 (0%)		0/44 (0%)		1/44 (2.3%)
Injury, poisoning and procedural complications
Epicondylitis	1/42 (2.4%)		0/44 (0%)		0/44 (0%)
Eye contusion	0/42 (0%)		1/44 (2.3%)		0/44 (0%)
Fall	0/42 (0%)		1/44 (2.3%)		0/44 (0%)
Meniscus injury	0/42 (0%)		1/44 (2.3%)		0/44 (0%)
Rib fracture	0/42 (0%)		1/44 (2.3%)		1/44 (2.3%)
Sternal fracture	0/42 (0%)		0/44 (0%)		1/44 (2.3%)
Animal bite	0/42 (0%)		1/44 (2.3%)		0/44 (0%)
Investigations
Blood creatine phosphokinase increased	1/42 (2.4%)		0/44 (0%)		0/44 (0%)
Blood glucose increased	1/42 (2.4%)		0/44 (0%)		0/44 (0%)
Blood uric acid decreased	0/42 (0%)		0/44 (0%)		2/44 (4.5%)
Glomerular filtration rate decreased	0/42 (0%)		1/44 (2.3%)		0/44 (0%)
Haematology test abnormal	0/42 (0%)		1/44 (2.3%)		0/44 (0%)
Liver function test increased	0/42 (0%)		1/44 (2.3%)		0/44 (0%)
Weight increased	0/42 (0%)		2/44 (4.5%)		0/44 (0%)
Metabolism and nutrition disorders
Decreased appetite	0/42 (0%)		1/44 (2.3%)		0/44 (0%)
Diabetes mellitus	1/42 (2.4%)		0/44 (0%)		0/44 (0%)
Diabetes mellitus inadequate control	0/42 (0%)		1/44 (2.3%)		1/44 (2.3%)
Gout	0/42 (0%)		0/44 (0%)		2/44 (4.5%)
Hypercalcaemia	0/42 (0%)		0/44 (0%)		1/44 (2.3%)
Hyperglycaemia	1/42 (2.4%)		0/44 (0%)		0/44 (0%)
Hyperkalaemia	0/42 (0%)		2/44 (4.5%)		0/44 (0%)
Hypoglycaemia	1/42 (2.4%)		2/44 (4.5%)		1/44 (2.3%)
Hypokalaemia	0/42 (0%)		1/44 (2.3%)		0/44 (0%)
Lactic acidosis	0/42 (0%)		1/44 (2.3%)		0/44 (0%)
Type 2 diabetes mellitus	0/42 (0%)		0/44 (0%)		1/44 (2.3%)
Musculoskeletal and connective tissue disorders
Arthralgia	0/42 (0%)		0/44 (0%)		2/44 (4.5%)
Exostosis	1/42 (2.4%)		0/44 (0%)		0/44 (0%)
Gouty arthritis	0/42 (0%)		0/44 (0%)		1/44 (2.3%)
Intervertebral disc degeneration	1/42 (2.4%)		0/44 (0%)		0/44 (0%)
Joint stiffness	1/42 (2.4%)		0/44 (0%)		0/44 (0%)
Lumbar spinal stenosis	1/42 (2.4%)		0/44 (0%)		0/44 (0%)
Muscle spasms	1/42 (2.4%)		0/44 (0%)		1/44 (2.3%)
Musculoskeletal pain	0/42 (0%)		0/44 (0%)		1/44 (2.3%)
Osteoarthritis	1/42 (2.4%)		0/44 (0%)		0/44 (0%)
Spinal column stenosis	0/42 (0%)		0/44 (0%)		1/44 (2.3%)
Spinal osteoarthritis	1/42 (2.4%)		1/44 (2.3%)		0/44 (0%)
Synovial cyst	0/42 (0%)		1/44 (2.3%)		0/44 (0%)
Tenosynovitis	1/42 (2.4%)		0/44 (0%)		0/44 (0%)
Trigger finger	1/42 (2.4%)		0/44 (0%)		0/44 (0%)
Nervous system disorders
Amnesia	0/42 (0%)		0/44 (0%)		1/44 (2.3%)
Carpal tunnel syndrome	0/42 (0%)		0/44 (0%)		1/44 (2.3%)
Dizziness	0/42 (0%)		0/44 (0%)		2/44 (4.5%)
Headache	2/42 (4.8%)		0/44 (0%)		1/44 (2.3%)
Hyperaesthesia	0/42 (0%)		0/44 (0%)		1/44 (2.3%)
Loss of consciousness	0/42 (0%)		1/44 (2.3%)		1/44 (2.3%)
Lumbar radiculopathy	1/42 (2.4%)		0/44 (0%)		0/44 (0%)
Neuropathy peripheral	0/42 (0%)		1/44 (2.3%)		0/44 (0%)
Paraesthesia	0/42 (0%)		0/44 (0%)		1/44 (2.3%)
Sinus headache	0/42 (0%)		0/44 (0%)		1/44 (2.3%)
Renal and urinary disorders
Micturition urgency	0/42 (0%)		1/44 (2.3%)		0/44 (0%)
Proteinuria	1/42 (2.4%)		0/44 (0%)		0/44 (0%)
Renal impairment	1/42 (2.4%)		1/44 (2.3%)		0/44 (0%)
Urinary retention	1/42 (2.4%)		0/44 (0%)		0/44 (0%)
Respiratory, thoracic and mediastinal disorders
Atelectasis	0/42 (0%)		1/44 (2.3%)		0/44 (0%)
Chronic obstructive pulmonary disease	0/42 (0%)		0/44 (0%)		1/44 (2.3%)
Cough	0/42 (0%)		1/44 (2.3%)		0/44 (0%)
Dyspnoea	1/42 (2.4%)		0/44 (0%)		0/44 (0%)
Nasal congestion	0/42 (0%)		1/44 (2.3%)		0/44 (0%)
Rhinitis allergic	0/42 (0%)		1/44 (2.3%)		0/44 (0%)
Rhonchi	0/42 (0%)		0/44 (0%)		1/44 (2.3%)
Sinus congestion	0/42 (0%)		1/44 (2.3%)		0/44 (0%)
Skin and subcutaneous tissue disorders
Dermatitis contact	1/42 (2.4%)		0/44 (0%)		0/44 (0%)
Vascular disorders
Angiopathy	0/42 (0%)		1/44 (2.3%)		0/44 (0%)
Hypertension	1/42 (2.4%)		1/44 (2.3%)		0/44 (0%)
Peripheral arterial occlusive disease	0/42 (0%)		1/44 (2.3%)		0/44 (0%)
Peripheral artery aneurysm	1/42 (2.4%)		0/44 (0%)		0/44 (0%)

Limitations/Caveats

[Not Specified]

More Information

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.