Trial Outcomes & Findings for A Study to Evaluate the Safety and Efficacy of TS-121 as an Adjunctive Treatment for Major Depressive Disorder (NCT NCT03093025)

Last Updated: 2020-07-14

Results Overview

The MADRS is a clinician-rated scale to assess depressive symptoms which consists from 10 items. The time frame for this scale is the past 7 days. Each item is scored on 7-point scale (0 \[absence of symptoms\] to 6 \[severe\]). The total score is the sum of 10 items and can take range from 0 to 60. A negative change from baseline indicates improvement.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

51 participants

Primary outcome timeframe

6 weeks

Results posted on

2020-07-14

Participant Flow

Participant milestones

Participant milestones
Measure	TS-121 10mg TS-121 10 mg: Orally taken once daily	TS-121 50mg TS-121 50 mg: Orally taken once daily	Placebo Placebo: Orally taken once daily
Overall Study STARTED	16	17	18
Overall Study COMPLETED	12	15	16
Overall Study NOT COMPLETED	4	2	2

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

A Study to Evaluate the Safety and Efficacy of TS-121 as an Adjunctive Treatment for Major Depressive Disorder

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	TS-121 10mg n=16 Participants TS-121 10 mg: Orally taken once daily	TS-121 50mg n=16 Participants TS-121 50 mg: Orally taken once daily	Placebo n=18 Participants Placebo: Orally taken once daily	Total n=50 Participants Total of all reporting groups
Age, Continuous	44.8 years STANDARD_DEVIATION 12.62 • n=5 Participants	44.8 years STANDARD_DEVIATION 12.93 • n=7 Participants	45.8 years STANDARD_DEVIATION 11.09 • n=5 Participants	45.1 years STANDARD_DEVIATION 11.95 • n=4 Participants
Sex: Female, Male Female	10 Participants n=5 Participants	11 Participants n=7 Participants	12 Participants n=5 Participants	33 Participants n=4 Participants
Sex: Female, Male Male	6 Participants n=5 Participants	5 Participants n=7 Participants	6 Participants n=5 Participants	17 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Asian	3 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants	6 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Black or African American	6 Participants n=5 Participants	4 Participants n=7 Participants	3 Participants n=5 Participants	13 Participants n=4 Participants
Race (NIH/OMB) White	7 Participants n=5 Participants	10 Participants n=7 Participants	12 Participants n=5 Participants	29 Participants n=4 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	2 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants

PRIMARY outcome

Timeframe: 6 weeks

Population: Participants who did not receive at least one dose of investigational product or did not have at least one post-dose assessments were not included in the analysis.

Outcome measures

Outcome measures
Measure	TS-121 10mg n=13 Participants TS-121 10 mg: Orally taken once daily	TS-121 50mg n=15 Participants TS-121 50 mg: Orally taken once daily	Placebo n=17 Participants Placebo: Orally taken once daily
Montgomery-Asberg Depression Rating Scale (MADRS)	-9.0 score on a scale Interval -13.9 to -4.1	-9.0 score on a scale Interval -13.4 to -4.5	-6.4 score on a scale Interval -10.7 to -2.2

SECONDARY outcome

Timeframe: 6 weeks

Population: Participants who did not receive at least one dose of investigational product or did not have at least one post-dose assessments were not included in the analysis.

The HAM-A is a clinician-rated scale to assess anxiety symptoms which consists from 14 items. The time frame for this scale is the past 7 days. Each item is scored on 5-point scale (0 \[absence of symptoms\] to 4 \[severe\]). The total score is the sum of 14 items and can take range from 0 to 56. A negative change from baseline indicates improvement.

Outcome measures

Outcome measures
Measure	TS-121 10mg n=13 Participants TS-121 10 mg: Orally taken once daily	TS-121 50mg n=15 Participants TS-121 50 mg: Orally taken once daily	Placebo n=17 Participants Placebo: Orally taken once daily
Hamilton Anxiety Scale (HAM-A)	-5.6 score on a scale Interval -8.1 to -3.1	-3.4 score on a scale Interval -5.7 to -1.2	-2.8 score on a scale Interval -5.0 to -0.6

SECONDARY outcome

Timeframe: 6 weeks

Population: Participants who did not receive at least one dose of investigational product or did not have at least one post-dose assessments were not included in the analysis.

The SDQ is a self-rated scale to assess the severity of symptoms across several subtypes of depression which consists from 44 items. The time frame for this scale is the past 7 days. Each item is scored on 6-point scale (1 \[better than normal\] to 6 \[severe\]). The total score is the sum of 44 items and can take range from 44 to 264. A negative change from baseline indicates improvement.

Outcome measures

Outcome measures
Measure	TS-121 10mg n=13 Participants TS-121 10 mg: Orally taken once daily	TS-121 50mg n=15 Participants TS-121 50 mg: Orally taken once daily	Placebo n=17 Participants Placebo: Orally taken once daily
Symptoms of Depression Questionnaire (SDQ)	-22.5 score on a scale Interval -34.1 to -11.0	-17.0 score on a scale Interval -27.5 to -6.5	-13.7 score on a scale Interval -23.8 to -3.7

SECONDARY outcome

Timeframe: 6 weeks

Population: Participants who did not receive at least one dose of investigational product or did not have at least one post-dose assessments were not included in the analysis.

The CGI-S is a clinician-rated scale to assess the severity of the disorder. The time frame for this scale is the past 7 days. The score ranges from 1 (Normal, not ill at all) to 7 (Among the most extremely ill patients).

Outcome measures

Outcome measures
Measure	TS-121 10mg n=13 Participants TS-121 10 mg: Orally taken once daily	TS-121 50mg n=15 Participants TS-121 50 mg: Orally taken once daily	Placebo n=17 Participants Placebo: Orally taken once daily
Clinical Global Impression-Severity (CGI-S)	-0.8 score on a scale Interval -1.4 to -0.3	-0.7 score on a scale Interval -1.2 to -0.2	-0.5 score on a scale Interval -1.0 to 0.0

SECONDARY outcome

Timeframe: 6 weeks

Percentage of MADRS responders (≥ 50% reduction in total score) at Week 6

Outcome measures

Outcome measures
Measure	TS-121 10mg n=12 Participants TS-121 10 mg: Orally taken once daily	TS-121 50mg n=15 Participants TS-121 50 mg: Orally taken once daily	Placebo n=16 Participants Placebo: Orally taken once daily
Montgomery-Asberg Depression Rating Scale (MADRS)	33.3 percentage of participants	20.0 percentage of participants	12.5 percentage of participants

SECONDARY outcome

Timeframe: 6 weeks

Percentage of CGI-I improvers ("Very much improved" or "Much improved") at Week 6

Outcome measures

Outcome measures
Measure	TS-121 10mg n=12 Participants TS-121 10 mg: Orally taken once daily	TS-121 50mg n=15 Participants TS-121 50 mg: Orally taken once daily	Placebo n=16 Participants Placebo: Orally taken once daily
Clinical Global Impression-Improvement (CGI-I)	33.3 percentage of participants	26.7 percentage of participants	18.8 percentage of participants

Adverse Events

TS-121 10mg

Serious events: 0 serious events

Other events: 7 other events

Deaths: 0 deaths

TS-121 50mg

Serious events: 0 serious events

Other events: 7 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 8 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Taisho Pharmaceutical R&D Inc. Study Director

Taisho Pharmaceutical R&D Inc.

Phone: 800-602-0203

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Other adverse events
Measure	TS-121 10mg n=16 participants at risk TS-121 10 mg: Orally taken once daily	TS-121 50mg n=16 participants at risk TS-121 50 mg: Orally taken once daily	Placebo n=18 participants at risk Placebo: Orally taken once daily
Eye disorders Diplopia	6.2% 1/16 • Number of events 1 • Onset date on or later than date of first dose of the randomized treatment through follow-up visit, an average of 8 weeks. One participant in TS-121 50 mg group did not take any dose of investigational product after randomization. Therefore, the participant was not included in analyses.	0.00% 0/16 • Onset date on or later than date of first dose of the randomized treatment through follow-up visit, an average of 8 weeks. One participant in TS-121 50 mg group did not take any dose of investigational product after randomization. Therefore, the participant was not included in analyses.	0.00% 0/18 • Onset date on or later than date of first dose of the randomized treatment through follow-up visit, an average of 8 weeks. One participant in TS-121 50 mg group did not take any dose of investigational product after randomization. Therefore, the participant was not included in analyses.
Eye disorders Eyelid oedema	0.00% 0/16 • Onset date on or later than date of first dose of the randomized treatment through follow-up visit, an average of 8 weeks. One participant in TS-121 50 mg group did not take any dose of investigational product after randomization. Therefore, the participant was not included in analyses.	6.2% 1/16 • Number of events 1 • Onset date on or later than date of first dose of the randomized treatment through follow-up visit, an average of 8 weeks. One participant in TS-121 50 mg group did not take any dose of investigational product after randomization. Therefore, the participant was not included in analyses.	0.00% 0/18 • Onset date on or later than date of first dose of the randomized treatment through follow-up visit, an average of 8 weeks. One participant in TS-121 50 mg group did not take any dose of investigational product after randomization. Therefore, the participant was not included in analyses.
Eye disorders Lenticular opacities	0.00% 0/16 • Onset date on or later than date of first dose of the randomized treatment through follow-up visit, an average of 8 weeks. One participant in TS-121 50 mg group did not take any dose of investigational product after randomization. Therefore, the participant was not included in analyses.	12.5% 2/16 • Number of events 2 • Onset date on or later than date of first dose of the randomized treatment through follow-up visit, an average of 8 weeks. One participant in TS-121 50 mg group did not take any dose of investigational product after randomization. Therefore, the participant was not included in analyses.	0.00% 0/18 • Onset date on or later than date of first dose of the randomized treatment through follow-up visit, an average of 8 weeks. One participant in TS-121 50 mg group did not take any dose of investigational product after randomization. Therefore, the participant was not included in analyses.
Eye disorders Vision blurred	6.2% 1/16 • Number of events 1 • Onset date on or later than date of first dose of the randomized treatment through follow-up visit, an average of 8 weeks. One participant in TS-121 50 mg group did not take any dose of investigational product after randomization. Therefore, the participant was not included in analyses.	0.00% 0/16 • Onset date on or later than date of first dose of the randomized treatment through follow-up visit, an average of 8 weeks. One participant in TS-121 50 mg group did not take any dose of investigational product after randomization. Therefore, the participant was not included in analyses.	0.00% 0/18 • Onset date on or later than date of first dose of the randomized treatment through follow-up visit, an average of 8 weeks. One participant in TS-121 50 mg group did not take any dose of investigational product after randomization. Therefore, the participant was not included in analyses.
Infections and infestations Cellulitis	6.2% 1/16 • Number of events 1 • Onset date on or later than date of first dose of the randomized treatment through follow-up visit, an average of 8 weeks. One participant in TS-121 50 mg group did not take any dose of investigational product after randomization. Therefore, the participant was not included in analyses.	0.00% 0/16 • Onset date on or later than date of first dose of the randomized treatment through follow-up visit, an average of 8 weeks. One participant in TS-121 50 mg group did not take any dose of investigational product after randomization. Therefore, the participant was not included in analyses.	0.00% 0/18 • Onset date on or later than date of first dose of the randomized treatment through follow-up visit, an average of 8 weeks. One participant in TS-121 50 mg group did not take any dose of investigational product after randomization. Therefore, the participant was not included in analyses.
Infections and infestations Gastroenteritis viral	0.00% 0/16 • Onset date on or later than date of first dose of the randomized treatment through follow-up visit, an average of 8 weeks. One participant in TS-121 50 mg group did not take any dose of investigational product after randomization. Therefore, the participant was not included in analyses.	0.00% 0/16 • Onset date on or later than date of first dose of the randomized treatment through follow-up visit, an average of 8 weeks. One participant in TS-121 50 mg group did not take any dose of investigational product after randomization. Therefore, the participant was not included in analyses.	5.6% 1/18 • Number of events 1 • Onset date on or later than date of first dose of the randomized treatment through follow-up visit, an average of 8 weeks. One participant in TS-121 50 mg group did not take any dose of investigational product after randomization. Therefore, the participant was not included in analyses.
Infections and infestations Haemorrhoid infection	0.00% 0/16 • Onset date on or later than date of first dose of the randomized treatment through follow-up visit, an average of 8 weeks. One participant in TS-121 50 mg group did not take any dose of investigational product after randomization. Therefore, the participant was not included in analyses.	0.00% 0/16 • Onset date on or later than date of first dose of the randomized treatment through follow-up visit, an average of 8 weeks. One participant in TS-121 50 mg group did not take any dose of investigational product after randomization. Therefore, the participant was not included in analyses.	5.6% 1/18 • Number of events 1 • Onset date on or later than date of first dose of the randomized treatment through follow-up visit, an average of 8 weeks. One participant in TS-121 50 mg group did not take any dose of investigational product after randomization. Therefore, the participant was not included in analyses.
Infections and infestations Influenza	6.2% 1/16 • Number of events 1 • Onset date on or later than date of first dose of the randomized treatment through follow-up visit, an average of 8 weeks. One participant in TS-121 50 mg group did not take any dose of investigational product after randomization. Therefore, the participant was not included in analyses.	0.00% 0/16 • Onset date on or later than date of first dose of the randomized treatment through follow-up visit, an average of 8 weeks. One participant in TS-121 50 mg group did not take any dose of investigational product after randomization. Therefore, the participant was not included in analyses.	5.6% 1/18 • Number of events 1 • Onset date on or later than date of first dose of the randomized treatment through follow-up visit, an average of 8 weeks. One participant in TS-121 50 mg group did not take any dose of investigational product after randomization. Therefore, the participant was not included in analyses.
Infections and infestations Localised infection	0.00% 0/16 • Onset date on or later than date of first dose of the randomized treatment through follow-up visit, an average of 8 weeks. One participant in TS-121 50 mg group did not take any dose of investigational product after randomization. Therefore, the participant was not included in analyses.	6.2% 1/16 • Number of events 1 • Onset date on or later than date of first dose of the randomized treatment through follow-up visit, an average of 8 weeks. One participant in TS-121 50 mg group did not take any dose of investigational product after randomization. Therefore, the participant was not included in analyses.	0.00% 0/18 • Onset date on or later than date of first dose of the randomized treatment through follow-up visit, an average of 8 weeks. One participant in TS-121 50 mg group did not take any dose of investigational product after randomization. Therefore, the participant was not included in analyses.
Infections and infestations Upper respiratory tract infection	0.00% 0/16 • Onset date on or later than date of first dose of the randomized treatment through follow-up visit, an average of 8 weeks. One participant in TS-121 50 mg group did not take any dose of investigational product after randomization. Therefore, the participant was not included in analyses.	0.00% 0/16 • Onset date on or later than date of first dose of the randomized treatment through follow-up visit, an average of 8 weeks. One participant in TS-121 50 mg group did not take any dose of investigational product after randomization. Therefore, the participant was not included in analyses.	11.1% 2/18 • Number of events 2 • Onset date on or later than date of first dose of the randomized treatment through follow-up visit, an average of 8 weeks. One participant in TS-121 50 mg group did not take any dose of investigational product after randomization. Therefore, the participant was not included in analyses.
Infections and infestations Urinary tract infection	0.00% 0/16 • Onset date on or later than date of first dose of the randomized treatment through follow-up visit, an average of 8 weeks. One participant in TS-121 50 mg group did not take any dose of investigational product after randomization. Therefore, the participant was not included in analyses.	12.5% 2/16 • Number of events 2 • Onset date on or later than date of first dose of the randomized treatment through follow-up visit, an average of 8 weeks. One participant in TS-121 50 mg group did not take any dose of investigational product after randomization. Therefore, the participant was not included in analyses.	0.00% 0/18 • Onset date on or later than date of first dose of the randomized treatment through follow-up visit, an average of 8 weeks. One participant in TS-121 50 mg group did not take any dose of investigational product after randomization. Therefore, the participant was not included in analyses.
Injury, poisoning and procedural complications Arthropod bite	0.00% 0/16 • Onset date on or later than date of first dose of the randomized treatment through follow-up visit, an average of 8 weeks. One participant in TS-121 50 mg group did not take any dose of investigational product after randomization. Therefore, the participant was not included in analyses.	6.2% 1/16 • Number of events 1 • Onset date on or later than date of first dose of the randomized treatment through follow-up visit, an average of 8 weeks. One participant in TS-121 50 mg group did not take any dose of investigational product after randomization. Therefore, the participant was not included in analyses.	0.00% 0/18 • Onset date on or later than date of first dose of the randomized treatment through follow-up visit, an average of 8 weeks. One participant in TS-121 50 mg group did not take any dose of investigational product after randomization. Therefore, the participant was not included in analyses.
Injury, poisoning and procedural complications Medication error	6.2% 1/16 • Number of events 1 • Onset date on or later than date of first dose of the randomized treatment through follow-up visit, an average of 8 weeks. One participant in TS-121 50 mg group did not take any dose of investigational product after randomization. Therefore, the participant was not included in analyses.	6.2% 1/16 • Number of events 2 • Onset date on or later than date of first dose of the randomized treatment through follow-up visit, an average of 8 weeks. One participant in TS-121 50 mg group did not take any dose of investigational product after randomization. Therefore, the participant was not included in analyses.	0.00% 0/18 • Onset date on or later than date of first dose of the randomized treatment through follow-up visit, an average of 8 weeks. One participant in TS-121 50 mg group did not take any dose of investigational product after randomization. Therefore, the participant was not included in analyses.
Nervous system disorders Disturbance in attention	0.00% 0/16 • Onset date on or later than date of first dose of the randomized treatment through follow-up visit, an average of 8 weeks. One participant in TS-121 50 mg group did not take any dose of investigational product after randomization. Therefore, the participant was not included in analyses.	6.2% 1/16 • Number of events 1 • Onset date on or later than date of first dose of the randomized treatment through follow-up visit, an average of 8 weeks. One participant in TS-121 50 mg group did not take any dose of investigational product after randomization. Therefore, the participant was not included in analyses.	0.00% 0/18 • Onset date on or later than date of first dose of the randomized treatment through follow-up visit, an average of 8 weeks. One participant in TS-121 50 mg group did not take any dose of investigational product after randomization. Therefore, the participant was not included in analyses.
Nervous system disorders Dizziness	0.00% 0/16 • Onset date on or later than date of first dose of the randomized treatment through follow-up visit, an average of 8 weeks. One participant in TS-121 50 mg group did not take any dose of investigational product after randomization. Therefore, the participant was not included in analyses.	6.2% 1/16 • Number of events 1 • Onset date on or later than date of first dose of the randomized treatment through follow-up visit, an average of 8 weeks. One participant in TS-121 50 mg group did not take any dose of investigational product after randomization. Therefore, the participant was not included in analyses.	0.00% 0/18 • Onset date on or later than date of first dose of the randomized treatment through follow-up visit, an average of 8 weeks. One participant in TS-121 50 mg group did not take any dose of investigational product after randomization. Therefore, the participant was not included in analyses.
Nervous system disorders Headache	6.2% 1/16 • Number of events 1 • Onset date on or later than date of first dose of the randomized treatment through follow-up visit, an average of 8 weeks. One participant in TS-121 50 mg group did not take any dose of investigational product after randomization. Therefore, the participant was not included in analyses.	6.2% 1/16 • Number of events 1 • Onset date on or later than date of first dose of the randomized treatment through follow-up visit, an average of 8 weeks. One participant in TS-121 50 mg group did not take any dose of investigational product after randomization. Therefore, the participant was not included in analyses.	0.00% 0/18 • Onset date on or later than date of first dose of the randomized treatment through follow-up visit, an average of 8 weeks. One participant in TS-121 50 mg group did not take any dose of investigational product after randomization. Therefore, the participant was not included in analyses.
Nervous system disorders Paraesthesia	0.00% 0/16 • Onset date on or later than date of first dose of the randomized treatment through follow-up visit, an average of 8 weeks. One participant in TS-121 50 mg group did not take any dose of investigational product after randomization. Therefore, the participant was not included in analyses.	0.00% 0/16 • Onset date on or later than date of first dose of the randomized treatment through follow-up visit, an average of 8 weeks. One participant in TS-121 50 mg group did not take any dose of investigational product after randomization. Therefore, the participant was not included in analyses.	5.6% 1/18 • Number of events 1 • Onset date on or later than date of first dose of the randomized treatment through follow-up visit, an average of 8 weeks. One participant in TS-121 50 mg group did not take any dose of investigational product after randomization. Therefore, the participant was not included in analyses.
Gastrointestinal disorders Constipation	6.2% 1/16 • Number of events 1 • Onset date on or later than date of first dose of the randomized treatment through follow-up visit, an average of 8 weeks. One participant in TS-121 50 mg group did not take any dose of investigational product after randomization. Therefore, the participant was not included in analyses.	0.00% 0/16 • Onset date on or later than date of first dose of the randomized treatment through follow-up visit, an average of 8 weeks. One participant in TS-121 50 mg group did not take any dose of investigational product after randomization. Therefore, the participant was not included in analyses.	0.00% 0/18 • Onset date on or later than date of first dose of the randomized treatment through follow-up visit, an average of 8 weeks. One participant in TS-121 50 mg group did not take any dose of investigational product after randomization. Therefore, the participant was not included in analyses.
Gastrointestinal disorders Nausea	6.2% 1/16 • Number of events 1 • Onset date on or later than date of first dose of the randomized treatment through follow-up visit, an average of 8 weeks. One participant in TS-121 50 mg group did not take any dose of investigational product after randomization. Therefore, the participant was not included in analyses.	0.00% 0/16 • Onset date on or later than date of first dose of the randomized treatment through follow-up visit, an average of 8 weeks. One participant in TS-121 50 mg group did not take any dose of investigational product after randomization. Therefore, the participant was not included in analyses.	5.6% 1/18 • Number of events 1 • Onset date on or later than date of first dose of the randomized treatment through follow-up visit, an average of 8 weeks. One participant in TS-121 50 mg group did not take any dose of investigational product after randomization. Therefore, the participant was not included in analyses.
Ear and labyrinth disorders Tinnitus	0.00% 0/16 • Onset date on or later than date of first dose of the randomized treatment through follow-up visit, an average of 8 weeks. One participant in TS-121 50 mg group did not take any dose of investigational product after randomization. Therefore, the participant was not included in analyses.	6.2% 1/16 • Number of events 1 • Onset date on or later than date of first dose of the randomized treatment through follow-up visit, an average of 8 weeks. One participant in TS-121 50 mg group did not take any dose of investigational product after randomization. Therefore, the participant was not included in analyses.	11.1% 2/18 • Number of events 2 • Onset date on or later than date of first dose of the randomized treatment through follow-up visit, an average of 8 weeks. One participant in TS-121 50 mg group did not take any dose of investigational product after randomization. Therefore, the participant was not included in analyses.
General disorders Oedema peripheral	0.00% 0/16 • Onset date on or later than date of first dose of the randomized treatment through follow-up visit, an average of 8 weeks. One participant in TS-121 50 mg group did not take any dose of investigational product after randomization. Therefore, the participant was not included in analyses.	6.2% 1/16 • Number of events 1 • Onset date on or later than date of first dose of the randomized treatment through follow-up visit, an average of 8 weeks. One participant in TS-121 50 mg group did not take any dose of investigational product after randomization. Therefore, the participant was not included in analyses.	0.00% 0/18 • Onset date on or later than date of first dose of the randomized treatment through follow-up visit, an average of 8 weeks. One participant in TS-121 50 mg group did not take any dose of investigational product after randomization. Therefore, the participant was not included in analyses.
Investigations Bacterial test positive	0.00% 0/16 • Onset date on or later than date of first dose of the randomized treatment through follow-up visit, an average of 8 weeks. One participant in TS-121 50 mg group did not take any dose of investigational product after randomization. Therefore, the participant was not included in analyses.	6.2% 1/16 • Number of events 1 • Onset date on or later than date of first dose of the randomized treatment through follow-up visit, an average of 8 weeks. One participant in TS-121 50 mg group did not take any dose of investigational product after randomization. Therefore, the participant was not included in analyses.	0.00% 0/18 • Onset date on or later than date of first dose of the randomized treatment through follow-up visit, an average of 8 weeks. One participant in TS-121 50 mg group did not take any dose of investigational product after randomization. Therefore, the participant was not included in analyses.
Investigations Blood creatinine increased	0.00% 0/16 • Onset date on or later than date of first dose of the randomized treatment through follow-up visit, an average of 8 weeks. One participant in TS-121 50 mg group did not take any dose of investigational product after randomization. Therefore, the participant was not included in analyses.	0.00% 0/16 • Onset date on or later than date of first dose of the randomized treatment through follow-up visit, an average of 8 weeks. One participant in TS-121 50 mg group did not take any dose of investigational product after randomization. Therefore, the participant was not included in analyses.	5.6% 1/18 • Number of events 1 • Onset date on or later than date of first dose of the randomized treatment through follow-up visit, an average of 8 weeks. One participant in TS-121 50 mg group did not take any dose of investigational product after randomization. Therefore, the participant was not included in analyses.
Investigations Crystal urine present	0.00% 0/16 • Onset date on or later than date of first dose of the randomized treatment through follow-up visit, an average of 8 weeks. One participant in TS-121 50 mg group did not take any dose of investigational product after randomization. Therefore, the participant was not included in analyses.	6.2% 1/16 • Number of events 1 • Onset date on or later than date of first dose of the randomized treatment through follow-up visit, an average of 8 weeks. One participant in TS-121 50 mg group did not take any dose of investigational product after randomization. Therefore, the participant was not included in analyses.	0.00% 0/18 • Onset date on or later than date of first dose of the randomized treatment through follow-up visit, an average of 8 weeks. One participant in TS-121 50 mg group did not take any dose of investigational product after randomization. Therefore, the participant was not included in analyses.
Musculoskeletal and connective tissue disorders Pain in extremity	6.2% 1/16 • Number of events 1 • Onset date on or later than date of first dose of the randomized treatment through follow-up visit, an average of 8 weeks. One participant in TS-121 50 mg group did not take any dose of investigational product after randomization. Therefore, the participant was not included in analyses.	0.00% 0/16 • Onset date on or later than date of first dose of the randomized treatment through follow-up visit, an average of 8 weeks. One participant in TS-121 50 mg group did not take any dose of investigational product after randomization. Therefore, the participant was not included in analyses.	0.00% 0/18 • Onset date on or later than date of first dose of the randomized treatment through follow-up visit, an average of 8 weeks. One participant in TS-121 50 mg group did not take any dose of investigational product after randomization. Therefore, the participant was not included in analyses.
Renal and urinary disorders Nephrolithiasis	0.00% 0/16 • Onset date on or later than date of first dose of the randomized treatment through follow-up visit, an average of 8 weeks. One participant in TS-121 50 mg group did not take any dose of investigational product after randomization. Therefore, the participant was not included in analyses.	6.2% 1/16 • Number of events 1 • Onset date on or later than date of first dose of the randomized treatment through follow-up visit, an average of 8 weeks. One participant in TS-121 50 mg group did not take any dose of investigational product after randomization. Therefore, the participant was not included in analyses.	0.00% 0/18 • Onset date on or later than date of first dose of the randomized treatment through follow-up visit, an average of 8 weeks. One participant in TS-121 50 mg group did not take any dose of investigational product after randomization. Therefore, the participant was not included in analyses.
Blood and lymphatic system disorders Anaemia	0.00% 0/16 • Onset date on or later than date of first dose of the randomized treatment through follow-up visit, an average of 8 weeks. One participant in TS-121 50 mg group did not take any dose of investigational product after randomization. Therefore, the participant was not included in analyses.	0.00% 0/16 • Onset date on or later than date of first dose of the randomized treatment through follow-up visit, an average of 8 weeks. One participant in TS-121 50 mg group did not take any dose of investigational product after randomization. Therefore, the participant was not included in analyses.	5.6% 1/18 • Number of events 1 • Onset date on or later than date of first dose of the randomized treatment through follow-up visit, an average of 8 weeks. One participant in TS-121 50 mg group did not take any dose of investigational product after randomization. Therefore, the participant was not included in analyses.
Psychiatric disorders Depression	0.00% 0/16 • Onset date on or later than date of first dose of the randomized treatment through follow-up visit, an average of 8 weeks. One participant in TS-121 50 mg group did not take any dose of investigational product after randomization. Therefore, the participant was not included in analyses.	0.00% 0/16 • Onset date on or later than date of first dose of the randomized treatment through follow-up visit, an average of 8 weeks. One participant in TS-121 50 mg group did not take any dose of investigational product after randomization. Therefore, the participant was not included in analyses.	5.6% 1/18 • Number of events 1 • Onset date on or later than date of first dose of the randomized treatment through follow-up visit, an average of 8 weeks. One participant in TS-121 50 mg group did not take any dose of investigational product after randomization. Therefore, the participant was not included in analyses.
Skin and subcutaneous tissue disorders Ingrowing nail	0.00% 0/16 • Onset date on or later than date of first dose of the randomized treatment through follow-up visit, an average of 8 weeks. One participant in TS-121 50 mg group did not take any dose of investigational product after randomization. Therefore, the participant was not included in analyses.	0.00% 0/16 • Onset date on or later than date of first dose of the randomized treatment through follow-up visit, an average of 8 weeks. One participant in TS-121 50 mg group did not take any dose of investigational product after randomization. Therefore, the participant was not included in analyses.	5.6% 1/18 • Number of events 1 • Onset date on or later than date of first dose of the randomized treatment through follow-up visit, an average of 8 weeks. One participant in TS-121 50 mg group did not take any dose of investigational product after randomization. Therefore, the participant was not included in analyses.