Phase 2 Study of TMX-049 in Subjects With Type 2 Diabetes... | NCT03449199

Label	Type	Description	Intervention Names
TMX-049 40 mg QD (Once Daily)	Experimental	TMX-049: 40 mg of TMX-049 to be taken orally, once daily	Drug: TMX-049
TMX-049 200 mg QD (Once Daily)	Experimental	TMX-049: 200 mg of TMX-049 to be taken orally, once daily	Drug: TMX-049
TMX-049 Placebo	Placebo Comparator		Drug: Placebo

Name	Type	Description	Arm Group Labels	Other Names
TMX-049	Drug	A certain dose of TMX-049 to be taken orally, once daily	TMX-049 200 mg QD (Once Daily) TMX-049 40 mg QD (Once Daily)

Measure	Description	Time Frame
Changes in Log-transformed Urinary Albumin-to-creatinine Ratio (UACR) at 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 and reported as a primary outcome.	Baseline and Week 12

Measure	Description	Time Frame
Changes in Estimated Glomerular Filtration Rate (GFR)	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.	Baseline and Week 2, 6, 12, 16 (Follow-up)

Name	Affiliation	Role
Michael Cressman, D.O.	Covance	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
AKDHC Medical Research Services, LLC		Flagstaff	Arizona	86001	United States
Aventiv Research Inc.

PubMed Identifier	Type	Citation	Retractions
35369650	Derived	Bakris GL, Mikami H, Hirata M, Nakajima A, Cressman MD. A Non-purine Xanthine Oxidoreductase Inhibitor Reduces Albuminuria in Patients with DKD: A Randomized Controlled Trial. Kidney360. 2021 Jun 30;2(8):1240-1250. doi: 10.34067/KID.0001672021. eCollection 2021 Aug 26.

ID	Title	Description
FG000	TMX-049 Placebo	Placebo: Matching placebo to be taken orally, once daily
FG001	TMX-049 40mg QD	TMX-049: 40mg of TMX-049 to be taken orally, once daily

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Feb 7, 2018	Apr 14, 2022

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Changes in Log-transformed Urinary Albumin-to-creatinine Ratio (UACR) at 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 and reported as a primary outcome.

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.

Posted

Least Squares Mean

Standard Error

Log(mg/g)

Baseline and Week 12

ID	Title	Description
OG000	TMX-049 Placebo	Placebo: Matching placebo to be taken orally, once daily, for 12 weeks
OG001	TMX-049 40 mg QD	TMX-049: 40 mg of TMX-049 to be taken orally, once daily for 12 weeks
OG002	TMX-049 200 mg QD	TMX-049: 200 mg of TMX-049 to be taken orally, once daily for 12 weeks

Units	Counts
Participants	OG00042 OG00143 OG00244

Title

Denominators

Categories

Title	Measurements
	OG000-0.10± 0.153 OG001-0.15± 0.151 OG002-0.53± 0.150

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	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.	ANCOVA		0.7953		LS Mean Difference	-0.05			2-Sided	95	-0.44	0.34					Superiority

Secondary

Changes in Estimated Glomerular Filtration Rate (GFR)

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.

Posted

Least Squares Mean

Standard Error

ml/min/1.73 m^2

Baseline and Week 2, 6, 12, 16 (Follow-up)

ID	Title	Description
OG000	TMX-049 Placebo	Placebo: Matching placebo to be taken orally, once daily for 12 weeks
OG001	TMX-049 40 mg QD	TMX-049:40 mg of TMX-049 to be taken orally, once daily for 12 weeks
OG002	TMX-049 200 mg QD	TMX-049: 200 mg of TMX-049 to be taken orally, once daily for 12 weeks

Secondary

Changes in Serum Uric Acid (sUA)

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.

Posted

Least Squares Mean

Standard Error

mg/dL

Baseline and Week 2, 6, 12, 16 (Follow-up)

ID	Title	Description
OG000	TMX-049 Placebo	Placebo: Matching placebo to be taken orally, once daily for 12 weeks
OG001	TMX-049 40 mg QD	TMX-049: 40 mg of TMX-049 to be taken orally, once daily for 12 weeks
OG002	TMX-049 200 mg QD	TMX-049: 200 mg of TMX-049 to be taken orally, once daily for 12 weeks

Units	Counts

Secondary

Changes in Urinary Albumin-to-Creatinine Ratio (UACR)

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

Posted

Least Squares Mean

Standard Error

mg/g

Baseline and Week 2, 6, 12, 16 (Follow-up)

ID	Title	Description
OG000	TMX-049 Placebo	Placebo: Matching placebo to be taken orally, once daily for 12 weeks
OG001	TMX-049 40 mg QD	TMX-049: 40 mg of TMX-049 to be taken orally, once daily for 12 weeks
OG002	TMX-049 200 mg QD	TMX-049: 200 mg of TMX-049 to be taken orally, once daily for 12 weeks

Units	Counts
Participants

Secondary

Proportion of Subjects With a Greater Than 30% Reduction From Baseline to Week 12 in Urinary Albumin-to-Creatinine Ratio

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.

Posted

Count of Participants

Participants

16 Weeks

ID	Title	Description
OG000	TMX-049 Placebo	Placebo: Matching placebo to be taken orally, once daily for 12 weeks
OG001	TMX-049 40 mg QD	TMX-049: 40 mg of TMX-049 to be taken orally, once daily for 12 weeks
OG002	TMX-049 200 mg QD	TMX-049: 200 mg of TMX-049 to be taken orally, once daily for 12 weeks

Secondary

Changes in Exploratory Blood Biomarkers (C Reactive Protein)

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.

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.

Posted

Mean

Standard Deviation

mg/dL

16 Weeks

ID	Title	Description
OG000	TMX-049 Placebo	Placebo: Matching placebo to be taken orally, once daily for 12 weeks
OG001	TMX-049 40 mg QD	TMX-049: 40 mg of TMX-049 to be taken orally, once daily for 12 weeks
OG002	TMX-049 200 mg QD	TMX-049: 200 mg of TMX-049 to be taken orally, once daily for 12 weeks

Units	Counts
Participants

Secondary

Changes in Exploratory Blood Biomarkers (Soluble TNF Receptor Type I)

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.

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.

Posted

Mean

Standard Deviation

ng/L

16 Weeks

ID	Title	Description
OG000	for 12 weeksTMX-049 Placebo	Placebo: Matching placebo to be taken orally, once daily for 12 weeks
OG001	TMX-049 40 mg QD	TMX-049: 40 mg of TMX-049 to be taken orally, once daily for 12 weeks
OG002	TMX-049 200 mg QD	TMX-049: 200 mg of TMX-049 to be taken orally, once daily for 12 weeks

Units	Counts
Participants

Secondary

Changes in Exploratory Renal Biomarkers (Creatinine-Corrected Fatty Acid Binding Protein 1)

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.

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.

Posted

Mean

Standard Deviation

ug/L/mg/dL

16 Weeks

ID	Title	Description
OG000	TMX-049 Placebo	Placebo: Matching placebo to be taken orally, once daily for 12 weeks
OG001	TMX-049 40 mg QD	TMX-049: 40 mg of TMX-049 to be taken orally, once daily for 12 weeks
OG002	TMX-049 200 mg QD	TMX-049: 200 mg of TMX-049 to be taken orally, once daily for 12 weeks

Units	Counts
Participants

Secondary

Changes in Exploratory Renal Biomarkers (Creatinine-Corrected Hydroxy Deoxyguanosine)

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.

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.

Posted

Mean

Standard Deviation

nmol/L/mg/dL

16 Weeks

ID	Title	Description
OG000	TMX-049 Placebo	Placebo: Matching placebo to be taken orally, once daily for 12 weeks
OG001	TMX-049 40 mg QD	TMX-049: 40 mg of TMX-049 to be taken orally, once daily for 12 weeks
OG002	TMX-049 200 mg QD	TMX-049: 200 mg of TMX-049 to be taken orally, once daily for 12 weeks

Units	Counts
Participants

Secondary

Changes in Exploratory Renal Biomarkers (Creatinine-Corrected Kidney Injury Molecule-1)

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.

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.

Posted

Mean

Standard Deviation

ug/L/mg/dL

16 Weeks

ID	Title	Description
OG000	TMX-049 Placebo	Placebo: Matching placebo to be taken orally, once daily for 12 weeks
OG001	TMX-049 40 mg QD	TMX-049: 40 mg of TMX-049 to be taken orally, once daily for 12 weeks
OG002	TMX-049 200 mg QD	TMX-049: 200 mg of TMX-049 to be taken orally, once daily for 12 weeks

Units	Counts
Participants

Secondary

Changes in Exploratory Renal Biomarkers (Creatinine-Corrected N-acetyl-beta-D-glucosaminidase)

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.

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.

Posted

Mean

Standard Deviation

U/L/mg/dL

16 Weeks

ID	Title	Description
OG000	TMX-049 Placebo	Placebo: Matching placebo to be taken orally, once daily for 12 weeks
OG001	TMX-049 40 mg QD	TMX-049: 40 mg of TMX-049 to be taken orally, once daily for 12 weeks
OG002	TMX-049 200 mg QD	TMX-049: 200 mg of TMX-049 to be taken orally, once daily for 12 weeks

Units	Counts
Participants

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA Version 20.1	Systematic Assessment	EG0001 affected42 at risk EG0011 affected44 at risk EG0020 affected44 at risk
Reticulocytosis	Blood and lymphatic system disorders	MedDRA Version 20.1	Systematic Assessment	EG0000 affected42 at risk EG0011 affected44 at risk EG0020 affected44 at risk
Bundle branch block right	Cardiac disorders	MedDRA Version 20.1	Systematic Assessment	EG0000 affected42 at risk EG0010 affected44 at risk EG0021 affected44 at risk
Palpitations	Cardiac disorders	MedDRA Version 20.1	Systematic Assessment	EG0001 affected42 at risk EG0010 affected44 at risk EG0020 affected44 at risk
Middle ear disorder	Ear and labyrinth disorders	MedDRA Version 20.1	Systematic Assessment	EG0000 affected42 at risk EG0010 affected44 at risk EG0021 affected44 at risk
Hypothyroidism	Endocrine disorders	MedDRA Version 20.1	Systematic Assessment	EG0000 affected42 at risk EG0012 affected44 at risk EG0020 affected44 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA Version 20.1	Systematic Assessment	EG0000 affected42 at risk EG0011 affected44 at risk EG0021 affected44 at risk
Abdominal pain lower	Gastrointestinal disorders	MedDRA Version 20.1	Systematic Assessment	EG0001 affected42 at risk EG0010 affected44 at risk EG0020 affected44 at risk
Constipation	Gastrointestinal disorders	MedDRA Version 20.1	Systematic Assessment	EG0001 affected42 at risk EG0011 affected44 at risk EG0020 affected44 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA Version 20.1	Systematic Assessment	EG0002 affected42 at risk EG0010 affected44 at risk EG0023 affected44 at risk
Dyspepsia	Gastrointestinal disorders	MedDRA Version 20.1	Systematic Assessment	EG0000 affected42 at risk EG0011 affected44 at risk EG0020 affected44 at risk
Haematemesis	Gastrointestinal disorders	MedDRA Version 20.1	Systematic Assessment	EG0000 affected42 at risk EG0011 affected44 at risk EG0020 affected44 at risk
Nausea	Gastrointestinal disorders	MedDRA Version 20.1	Systematic Assessment	EG0000 affected42 at risk EG0013 affected44 at risk EG0023 affected44 at risk
Oesophageal pain	Gastrointestinal disorders	MedDRA Version 20.1	Systematic Assessment	EG0000 affected42 at risk EG0010 affected44 at risk EG0021 affected44 at risk
Vomiting	Gastrointestinal disorders	MedDRA Version 20.1	Systematic Assessment	EG0001 affected42 at risk EG0011 affected44 at risk EG0021 affected44 at risk
Chest pain	General disorders	MedDRA Version 20.1	Systematic Assessment	EG0001 affected42 at risk EG0010 affected44 at risk EG0020 affected44 at risk
Drug interaction	General disorders	MedDRA Version 20.1	Systematic Assessment	EG0000 affected42 at risk EG0011 affected44 at risk EG0020 affected44 at risk
Oedema	General disorders	MedDRA Version 20.1	Systematic Assessment	EG0001 affected42 at risk EG0012 affected44 at risk EG0020 affected44 at risk
Oedema peripheral	General disorders	MedDRA Version 20.1	Systematic Assessment	EG0001 affected42 at risk EG0013 affected44 at risk EG0020 affected44 at risk
Pyrexia	General disorders	MedDRA Version 20.1	Systematic Assessment	EG0000 affected42 at risk EG0011 affected44 at risk EG0020 affected44 at risk
Drug hypersensitivity	Immune system disorders	MedDRA Version 20.1	Systematic Assessment	EG0000 affected42 at risk EG0010 affected44 at risk EG0021 affected44 at risk
Cellulitis	Infections and infestations	MedDRA Version 20.1	Systematic Assessment	EG0000 affected42 at risk EG0011 affected44 at risk EG0020 affected44 at risk
Gastroenteritis	Infections and infestations	MedDRA Version 20.1	Systematic Assessment	EG0000 affected42 at risk EG0011 affected44 at risk EG0020 affected44 at risk
Influenza	Infections and infestations	MedDRA Version 20.1	Systematic Assessment	EG0000 affected42 at risk EG0012 affected44 at risk EG0020 affected44 at risk
Lower respiratory tract infection	Infections and infestations	MedDRA Version 20.1	Systematic Assessment	EG0001 affected42 at risk EG0010 affected44 at risk EG0020 affected44 at risk
Nasopharyngitis	Infections and infestations	MedDRA Version 20.1	Systematic Assessment	EG0003 affected42 at risk EG0010 affected44 at risk EG0021 affected44 at risk
Sinusitis	Infections and infestations	MedDRA Version 20.1	Systematic Assessment	EG0001 affected42 at risk EG0011 affected44 at risk EG0020 affected44 at risk
Subcutaneous abscess	Infections and infestations	MedDRA Version 20.1	Systematic Assessment	EG0000 affected42 at risk EG0011 affected44 at risk EG0020 affected44 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA Version 20.1	Systematic Assessment	EG0000 affected42 at risk EG0012 affected44 at risk EG0020 affected44 at risk
Urinary tract infection	Infections and infestations	MedDRA Version 20.1	Systematic Assessment	EG0003 affected42 at risk EG0011 affected44 at risk EG0021 affected44 at risk
Urinary tract infection bacterial	Infections and infestations	MedDRA Version 20.1	Systematic Assessment	EG0000 affected42 at risk EG0010 affected44 at risk EG0021 affected44 at risk
Viral infection	Infections and infestations	MedDRA Version 20.1	Systematic Assessment	EG0001 affected42 at risk EG0010 affected44 at risk EG0020 affected44 at risk
Epicondylitis	Injury, poisoning and procedural complications	MedDRA Version 20.1	Systematic Assessment	EG0001 affected42 at risk EG0010 affected44 at risk EG0020 affected44 at risk
Eye contusion	Injury, poisoning and procedural complications	MedDRA Version 20.1	Systematic Assessment	EG0000 affected42 at risk EG0011 affected44 at risk EG0020 affected44 at risk
Fall	Injury, poisoning and procedural complications	MedDRA Version 20.1	Systematic Assessment	EG0000 affected42 at risk EG0011 affected44 at risk EG0020 affected44 at risk
Meniscus injury	Injury, poisoning and procedural complications	MedDRA Version 20.1	Systematic Assessment	EG0000 affected42 at risk EG0011 affected44 at risk EG0020 affected44 at risk
Rib fracture	Injury, poisoning and procedural complications	MedDRA Version 20.1	Systematic Assessment	EG0000 affected42 at risk EG0011 affected44 at risk EG0021 affected44 at risk
Sternal fracture	Injury, poisoning and procedural complications	MedDRA Version 20.1	Systematic Assessment	EG0000 affected42 at risk EG0010 affected44 at risk EG0021 affected44 at risk
Blood creatine phosphokinase increased	Investigations	MedDRA Version 20.1	Systematic Assessment	EG0001 affected42 at risk EG0010 affected44 at risk EG0020 affected44 at risk
Blood glucose increased	Investigations	MedDRA Version 20.1	Systematic Assessment	EG0001 affected42 at risk EG0010 affected44 at risk EG0020 affected44 at risk
Blood uric acid decreased	Investigations	MedDRA Version 20.1	Systematic Assessment	EG0000 affected42 at risk EG0010 affected44 at risk EG0022 affected44 at risk
Glomerular filtration rate decreased	Investigations	MedDRA Version 20.1	Systematic Assessment	EG0000 affected42 at risk EG0011 affected44 at risk EG0020 affected44 at risk
Haematology test abnormal	Investigations	MedDRA Version 20.1	Systematic Assessment	EG0000 affected42 at risk EG0011 affected44 at risk EG0020 affected44 at risk
Liver function test increased	Investigations	MedDRA Version 20.1	Systematic Assessment	EG0000 affected42 at risk EG0011 affected44 at risk EG0020 affected44 at risk
Weight increased	Investigations	MedDRA Version 20.1	Systematic Assessment	EG0000 affected42 at risk EG0012 affected44 at risk EG0020 affected44 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA Version 20.1	Systematic Assessment	EG0000 affected42 at risk EG0011 affected44 at risk EG0020 affected44 at risk
Diabetes mellitus	Metabolism and nutrition disorders	MedDRA Version 20.1	Systematic Assessment	EG0001 affected42 at risk EG0010 affected44 at risk EG0020 affected44 at risk
Diabetes mellitus inadequate control	Metabolism and nutrition disorders	MedDRA Version 20.1	Systematic Assessment	EG0000 affected42 at risk EG0011 affected44 at risk EG0021 affected44 at risk
Gout	Metabolism and nutrition disorders	MedDRA Version 20.1	Systematic Assessment	EG0000 affected42 at risk EG0010 affected44 at risk EG0022 affected44 at risk
Hypercalcaemia	Metabolism and nutrition disorders	MedDRA Version 20.1	Systematic Assessment	EG0000 affected42 at risk EG0010 affected44 at risk EG0021 affected44 at risk
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA Version 20.1	Systematic Assessment	EG0001 affected42 at risk EG0010 affected44 at risk EG0020 affected44 at risk
Hyperkalaemia	Metabolism and nutrition disorders	MedDRA Version 20.1	Systematic Assessment	EG0000 affected42 at risk EG0012 affected44 at risk EG0020 affected44 at risk
Hypoglycaemia	Metabolism and nutrition disorders	MedDRA Version 20.1	Systematic Assessment	EG0001 affected42 at risk EG0012 affected44 at risk EG0021 affected44 at risk
Hypokalaemia	Metabolism and nutrition disorders	MedDRA Version 20.1	Systematic Assessment	EG0000 affected42 at risk EG0011 affected44 at risk EG0020 affected44 at risk
Lactic acidosis	Metabolism and nutrition disorders	MedDRA Version 20.1	Systematic Assessment	EG0000 affected42 at risk EG0011 affected44 at risk EG0020 affected44 at risk
Type 2 diabetes mellitus	Metabolism and nutrition disorders	MedDRA Version 20.1	Systematic Assessment	EG0000 affected42 at risk EG0010 affected44 at risk EG0021 affected44 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA Version 20.1	Systematic Assessment	EG0000 affected42 at risk EG0010 affected44 at risk EG0022 affected44 at risk
Exostosis	Musculoskeletal and connective tissue disorders	MedDRA Version 20.1	Systematic Assessment	EG0001 affected42 at risk EG0010 affected44 at risk EG0020 affected44 at risk
Gouty arthritis	Musculoskeletal and connective tissue disorders	MedDRA Version 20.1	Systematic Assessment	EG0000 affected42 at risk EG0010 affected44 at risk EG0021 affected44 at risk
Intervertebral disc degeneration	Musculoskeletal and connective tissue disorders	MedDRA Version 20.1	Systematic Assessment	EG0001 affected42 at risk EG0010 affected44 at risk EG0020 affected44 at risk
Joint stiffness	Musculoskeletal and connective tissue disorders	MedDRA Version 20.1	Systematic Assessment	EG0001 affected42 at risk EG0010 affected44 at risk EG0020 affected44 at risk
Lumbar spinal stenosis	Musculoskeletal and connective tissue disorders	MedDRA Version 20.1	Systematic Assessment	EG0001 affected42 at risk EG0010 affected44 at risk EG0020 affected44 at risk
Muscle spasms	Musculoskeletal and connective tissue disorders	MedDRA Version 20.1	Systematic Assessment	EG0001 affected42 at risk EG0010 affected44 at risk EG0021 affected44 at risk
Musculoskeletal pain	Musculoskeletal and connective tissue disorders	MedDRA Version 20.1	Systematic Assessment	EG0000 affected42 at risk EG0010 affected44 at risk EG0021 affected44 at risk
Osteoarthritis	Musculoskeletal and connective tissue disorders	MedDRA Version 20.1	Systematic Assessment	EG0001 affected42 at risk EG0010 affected44 at risk EG0020 affected44 at risk
Spinal column stenosis	Musculoskeletal and connective tissue disorders	MedDRA Version 20.1	Systematic Assessment	EG0000 affected42 at risk EG0010 affected44 at risk EG0021 affected44 at risk
Spinal osteoarthritis	Musculoskeletal and connective tissue disorders	MedDRA Version 20.1	Systematic Assessment	EG0001 affected42 at risk EG0011 affected44 at risk EG0020 affected44 at risk
Synovial cyst	Musculoskeletal and connective tissue disorders	MedDRA Version 20.1	Systematic Assessment	EG0000 affected42 at risk EG0011 affected44 at risk EG0020 affected44 at risk
Tenosynovitis	Musculoskeletal and connective tissue disorders	MedDRA Version 20.1	Systematic Assessment	EG0001 affected42 at risk EG0010 affected44 at risk EG0020 affected44 at risk
Trigger finger	Musculoskeletal and connective tissue disorders	MedDRA Version 20.1	Systematic Assessment	EG0001 affected42 at risk EG0010 affected44 at risk EG0020 affected44 at risk
Amnesia	Nervous system disorders	MedDRA Version 20.1	Systematic Assessment	EG0000 affected42 at risk EG0010 affected44 at risk EG0021 affected44 at risk
Carpal tunnel syndrome	Nervous system disorders	MedDRA Version 20.1	Systematic Assessment	EG0000 affected42 at risk EG0010 affected44 at risk EG0021 affected44 at risk
Dizziness	Nervous system disorders	MedDRA Version 20.1	Systematic Assessment	EG0000 affected42 at risk EG0010 affected44 at risk EG0022 affected44 at risk
Headache	Nervous system disorders	MedDRA Version 20.1	Systematic Assessment	EG0002 affected42 at risk EG0010 affected44 at risk EG0021 affected44 at risk
Hyperaesthesia	Nervous system disorders	MedDRA Version 20.1	Systematic Assessment	EG0000 affected42 at risk EG0010 affected44 at risk EG0021 affected44 at risk
Loss of consciousness	Nervous system disorders	MedDRA Version 20.1	Systematic Assessment	EG0000 affected42 at risk EG0011 affected44 at risk EG0021 affected44 at risk
Lumbar radiculopathy	Nervous system disorders	MedDRA Version 20.1	Systematic Assessment	EG0001 affected42 at risk EG0010 affected44 at risk EG0020 affected44 at risk
Neuropathy peripheral	Nervous system disorders	MedDRA Version 20.1	Systematic Assessment	EG0000 affected42 at risk EG0011 affected44 at risk EG0020 affected44 at risk
Paraesthesia	Nervous system disorders	MedDRA Version 20.1	Systematic Assessment	EG0000 affected42 at risk EG0010 affected44 at risk EG0021 affected44 at risk
Sinus headache	Nervous system disorders	MedDRA Version 20.1	Systematic Assessment	EG0000 affected42 at risk EG0010 affected44 at risk EG0021 affected44 at risk
Micturition urgency	Renal and urinary disorders	MedDRA Version 20.1	Systematic Assessment	EG0000 affected42 at risk EG0011 affected44 at risk EG0020 affected44 at risk
Proteinuria	Renal and urinary disorders	MedDRA Version 20.1	Systematic Assessment	EG0001 affected42 at risk EG0010 affected44 at risk EG0020 affected44 at risk
Renal impairment	Renal and urinary disorders	MedDRA Version 20.1	Systematic Assessment	EG0001 affected42 at risk EG0011 affected44 at risk EG0020 affected44 at risk
Urinary retention	Renal and urinary disorders	MedDRA Version 20.1	Systematic Assessment	EG0001 affected42 at risk EG0010 affected44 at risk EG0020 affected44 at risk
Atelectasis	Respiratory, thoracic and mediastinal disorders	MedDRA Version 20.1	Systematic Assessment	EG0000 affected42 at risk EG0011 affected44 at risk EG0020 affected44 at risk
Chronic obstructive pulmonary disease	Respiratory, thoracic and mediastinal disorders	MedDRA Version 20.1	Systematic Assessment	EG0000 affected42 at risk EG0010 affected44 at risk EG0021 affected44 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA Version 20.1	Systematic Assessment	EG0000 affected42 at risk EG0011 affected44 at risk EG0020 affected44 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA Version 20.1	Systematic Assessment	EG0001 affected42 at risk EG0010 affected44 at risk EG0020 affected44 at risk
Nasal congestion	Respiratory, thoracic and mediastinal disorders	MedDRA Version 20.1	Systematic Assessment	EG0000 affected42 at risk EG0011 affected44 at risk EG0020 affected44 at risk
Rhinitis allergic	Respiratory, thoracic and mediastinal disorders	MedDRA Version 20.1	Systematic Assessment	EG0000 affected42 at risk EG0011 affected44 at risk EG0020 affected44 at risk
Rhonchi	Respiratory, thoracic and mediastinal disorders	MedDRA Version 20.1	Systematic Assessment	EG0000 affected42 at risk EG0010 affected44 at risk EG0021 affected44 at risk
Sinus congestion	Respiratory, thoracic and mediastinal disorders	MedDRA Version 20.1	Systematic Assessment	EG0000 affected42 at risk EG0011 affected44 at risk EG0020 affected44 at risk
Dermatitis contact	Skin and subcutaneous tissue disorders	MedDRA Version 20.1	Systematic Assessment	EG0001 affected42 at risk EG0010 affected44 at risk EG0020 affected44 at risk
Angiopathy	Vascular disorders	MedDRA Version 20.1	Systematic Assessment	EG0000 affected42 at risk EG0011 affected44 at risk EG0020 affected44 at risk
Hypertension	Vascular disorders	MedDRA Version 20.1	Systematic Assessment	EG0001 affected42 at risk EG0011 affected44 at risk EG0020 affected44 at risk
Peripheral arterial occlusive disease	Vascular disorders	MedDRA Version 20.1	Systematic Assessment	EG0000 affected42 at risk EG0011 affected44 at risk EG0020 affected44 at risk
Peripheral artery aneurysm	Vascular disorders	MedDRA Version 20.1	Systematic Assessment	EG0001 affected42 at risk EG0010 affected44 at risk EG0020 affected44 at risk
Abscess limb	Infections and infestations	MedDRA Version 20.1	Systematic Assessment	EG0000 affected42 at risk EG0010 affected44 at risk EG0021 affected44 at risk
Animal bite	Injury, poisoning and procedural complications	MedDRA Version 20.1	Systematic Assessment	EG0000 affected42 at risk EG0011 affected44 at risk EG0020 affected44 at risk

ID	Term
D007674	Kidney Diseases
D014570	Urologic Diseases
D052776	Female Urogenital Diseases
D005261	Female Urogenital Diseases and Pregnancy Complications
D000091642	Urogenital Diseases
D052801	Male Urogenital Diseases
D048909	Diabetes Complications
D003920	Diabetes Mellitus
D004700	Endocrine System Diseases

ID	Title	Description
BG000	TMX-049 Placebo	Placebo: Matching placebo to be taken orally, once daily
BG001	TMX-049 40 mg QD	TMX-049: 40 mg of TMX-049 to be taken orally, once daily
BG002	TMX-049 200 mg QD	TMX-049: 200 mg of TMX-049 to be taken orally, once daily
BG003	Total	Total of all reporting groups

ID	Title	Description	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	TMX-049 Placebo	Placebo: Matching placebo to be taken orally, once daily	42	4	42	18	42
EG001	TMX-049 40 mg QD	TMX-049: 40 mg of TMX-049 to be taken orally, once daily	44	4	44	19	44
EG002	TMX-049: 200 mg	TMX-049: 200 mg of TMX-049 to be taken orally, once daily	44	2	44	17	44

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Cardiac failure chronic	Cardiac disorders	MedDRA Version 20.1	Systematic Assessment	EG0001 affected42 at risk EG0010 affected44 at risk EG0020 affected44 at risk
Pancreatitis acute	Gastrointestinal disorders	MedDRA Version 20.1	Systematic Assessment	EG0000 affected42 at risk EG0011 affected44 at risk EG0020 affected44 at risk
Cholecystitis infective	Infections and infestations	MedDRA Version 20.1	Systematic Assessment	EG0001 affected42 at risk EG0010 affected44 at risk EG0020 affected44 at risk
Pneumonia	Infections and infestations	MedDRA Version 20.1	Systematic Assessment	EG0001 affected42 at risk EG0010 affected44 at risk EG0020 affected44 at risk
Sepsis	Infections and infestations	MedDRA Version 20.1	Systematic Assessment	EG0000 affected42 at risk EG0011 affected44 at risk EG0020 affected44 at risk
Hypoglycaemia	Metabolism and nutrition disorders	MedDRA Version 20.1	Systematic Assessment	EG0000 affected42 at risk EG0011 affected44 at risk EG0020 affected44 at risk
Myelodysplastic syndrome	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA Version 20.1	Systematic Assessment	EG0000 affected42 at risk EG0011 affected44 at risk EG0020 affected44 at risk
Loss of consciousness	Nervous system disorders	MedDRA Version 20.1	Systematic Assessment	EG0000 affected42 at risk EG0010 affected44 at risk EG0021 affected44 at risk
Lumbar radiculopathy	Nervous system disorders	MedDRA Version 20.1	Systematic Assessment	EG0001 affected42 at risk EG0010 affected44 at risk EG0020 affected44 at risk
Acute kidney injury	Renal and urinary disorders	MedDRA Version 20.1	Systematic Assessment	EG0001 affected42 at risk EG0011 affected44 at risk EG0020 affected44 at risk
Asthma	Respiratory, thoracic and mediastinal disorders	MedDRA Version 20.1	Systematic Assessment	EG0001 affected42 at risk EG0010 affected44 at risk EG0020 affected44 at risk
Chronic obstructive pulmonary disease	Respiratory, thoracic and mediastinal disorders	MedDRA Version 20.1	Systematic Assessment	EG0000 affected42 at risk EG0010 affected44 at risk EG0021 affected44 at risk
Respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA Version 20.1	Systematic Assessment	EG0001 affected42 at risk EG0010 affected44 at risk EG0020 affected44 at risk