Trial Outcomes & Findings for A Phase 2 Dose-finding Study of TAK-272 in Participants With Type 2 Diabetes Mellitus and Microalbuminuria (NCT NCT02332824)

Last Updated: 2018-08-13

Results Overview

The first morning void urine (the first urine immediately after rising prior to activities in standing position in the morning) samples on the day of each visit, and 1 day and 2 days before the day of each visit (3 consecutive days) were collected to calculate UACR.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

415 participants

Primary outcome timeframe

Week 0 and Week 12

Results posted on

2018-08-13

Participant Flow

Participants took part in the study at 81 investigative sites in Japan from 16 Oct 2014 to 18 Aug 2016.

Participants with a diagnosis of type 2 diabetes mellitus and microalbuminuria (early-stage nephropathy \[Stage 2\] patients with type 2 diabetes mellitus) were randomized in 1:1:1:1:1:1 to either of TAK-272 5 mg, 20 mg, 40 mg, 80 mg, candesartan cilexetil 8 mg or Placebo and administered tablets orally once daily for 12 weeks in double-blind manner.

Participant milestones

Participant milestones
Measure	Placebo TAK-272 placebo, 4 tablets, and Candesartan cilexetil placebo one tablet, orally, once daily for up to 12 weeks. Participants were administered TAK-272 placebo 4 tablets and Candesartan cilexetil placebo one tablet for 4 weeks (Week -4 to 0) in placebo run-in period and follow-up period (Week 12-14).	TAK-272 5 mg TAK-272 5 mg, one tablet, TAK-272 placebo 3 tablets, and Candesartan cilexetil placebo one tablet, orally, once daily for up to 12 weeks. Participants were administered TAK-272 placebo 4 tablets and Candesartan cilexetil placebo one tablet for 4 weeks (Week -4 to 0) in placebo run-in period and follow-up period (Week 12-14).	TAK-272 20 mg TAK-272 20 mg, one tablet, TAK-272 placebo 3 tablets, and Candesartan cilexetil placebo one tablet, orally, once daily for up to 12 weeks. Participants were administered TAK-272 placebo 4 tablets and Candesartan cilexetil placebo one tablet for 4 weeks (Week -4 to 0) in placebo run-in period and follow-up period (Week 12-14).	TAK-272 40 mg TAK-272 20 mg, 2 tablets, TAK-272 placebo 2 tablets, and Candesartan cilexetil placebo one tablet, orally, once daily for up to 12 weeks. Participants were administered TAK-272 placebo 4 tablets and Candesartan cilexetil placebo one tablet for 4 weeks (Week -4 to 0) in placebo run-in period and follow-up period (Week 12-14).	TAK-272 80 mg TAK-272 20 mg, 4 tablets, and Candesartan cilexetil placebo one tablet, orally, once daily for up to 12 weeks. Participants were administered TAK-272 placebo 4 tablets and Candesartan cilexetil placebo one tablet for 4 weeks (Week -4 to 0) in placebo run-in period and follow-up period (Week 12-14).	Candesartan Cilexetil 8 mg Candesartan cilexetil 8 mg, one tablet, and TAK-272 placebo 4 tablets, orally, once daily for up to 12 weeks. Participants were administered TAK-272 placebo 4 tablets and Candesartan cilexetil placebo one tablet for 4 weeks (Week -4 to 0) in placebo run-in period and follow-up period (Week 12-14).
Overall Study STARTED	67	67	74	68	69	70
Overall Study COMPLETED	61	66	72	66	65	69
Overall Study NOT COMPLETED	6	1	2	2	4	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo TAK-272 placebo, 4 tablets, and Candesartan cilexetil placebo one tablet, orally, once daily for up to 12 weeks. Participants were administered TAK-272 placebo 4 tablets and Candesartan cilexetil placebo one tablet for 4 weeks (Week -4 to 0) in placebo run-in period and follow-up period (Week 12-14).	TAK-272 5 mg TAK-272 5 mg, one tablet, TAK-272 placebo 3 tablets, and Candesartan cilexetil placebo one tablet, orally, once daily for up to 12 weeks. Participants were administered TAK-272 placebo 4 tablets and Candesartan cilexetil placebo one tablet for 4 weeks (Week -4 to 0) in placebo run-in period and follow-up period (Week 12-14).	TAK-272 20 mg TAK-272 20 mg, one tablet, TAK-272 placebo 3 tablets, and Candesartan cilexetil placebo one tablet, orally, once daily for up to 12 weeks. Participants were administered TAK-272 placebo 4 tablets and Candesartan cilexetil placebo one tablet for 4 weeks (Week -4 to 0) in placebo run-in period and follow-up period (Week 12-14).	TAK-272 40 mg TAK-272 20 mg, 2 tablets, TAK-272 placebo 2 tablets, and Candesartan cilexetil placebo one tablet, orally, once daily for up to 12 weeks. Participants were administered TAK-272 placebo 4 tablets and Candesartan cilexetil placebo one tablet for 4 weeks (Week -4 to 0) in placebo run-in period and follow-up period (Week 12-14).	TAK-272 80 mg TAK-272 20 mg, 4 tablets, and Candesartan cilexetil placebo one tablet, orally, once daily for up to 12 weeks. Participants were administered TAK-272 placebo 4 tablets and Candesartan cilexetil placebo one tablet for 4 weeks (Week -4 to 0) in placebo run-in period and follow-up period (Week 12-14).	Candesartan Cilexetil 8 mg Candesartan cilexetil 8 mg, one tablet, and TAK-272 placebo 4 tablets, orally, once daily for up to 12 weeks. Participants were administered TAK-272 placebo 4 tablets and Candesartan cilexetil placebo one tablet for 4 weeks (Week -4 to 0) in placebo run-in period and follow-up period (Week 12-14).
Overall Study Pretreatment Event/Adverse Event	4	0	1	1	4	1
Overall Study Voluntary Withdrawal	1	0	0	0	0	0
Overall Study Inconvenient schedule	1	1	0	0	0	0
Overall Study Transfer	0	0	1	1	0	0

Baseline Characteristics

The analyzed numbers for each arm were participants who were evaluable for this baseline characteristic.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=67 Participants TAK-272 placebo, 4 tablets, and Candesartan cilexetil placebo one tablet, orally, once daily for up to 12 weeks. Participants were administered TAK-272 placebo 4 tablets and Candesartan cilexetil placebo one tablet for 4 weeks (Week -4 to 0) in placebo run-in period and follow-up period (Week 12-14).	TAK-272 5 mg n=67 Participants TAK-272 5 mg, one tablet, TAK-272 placebo 3 tablets, and Candesartan cilexetil placebo one tablet, orally, once daily for up to 12 weeks. Participants were administered TAK-272 placebo 4 tablets and Candesartan cilexetil placebo one tablet for 4 weeks (Week -4 to 0) in placebo run-in period and follow-up period (Week 12-14).	TAK-272 20 mg n=74 Participants TAK-272 20 mg, one tablet, TAK-272 placebo 3 tablets, and Candesartan cilexetil placebo one tablet, orally, once daily for up to 12 weeks. Participants were administered TAK-272 placebo 4 tablets and Candesartan cilexetil placebo one tablet for 4 weeks (Week -4 to 0) in placebo run-in period and follow-up period (Week 12-14).	TAK-272 40 mg n=68 Participants TAK-272 20 mg, 2 tablets, TAK-272 placebo 2 tablets, and Candesartan cilexetil placebo one tablet, orally, once daily for up to 12 weeks. Participants were administered TAK-272 placebo 4 tablets and Candesartan cilexetil placebo one tablet for 4 weeks (Week -4 to 0) in placebo run-in period and follow-up period (Week 12-14).	TAK-272 80 mg n=69 Participants TAK-272 20 mg, 4 tablets, and Candesartan cilexetil placebo one tablet, orally, once daily for up to 12 weeks. Participants were administered TAK-272 placebo 4 tablets and Candesartan cilexetil placebo one tablet for 4 weeks (Week -4 to 0) in placebo run-in period and follow-up period (Week 12-14).	Candesartan Cilexetil 8 mg n=70 Participants Candesartan cilexetil 8 mg, one tablet, and TAK-272 placebo 4 tablets, orally, once daily for up to 12 weeks. Participants were administered TAK-272 placebo 4 tablets and Candesartan cilexetil placebo one tablet for 4 weeks (Week -4 to 0) in placebo run-in period and follow-up period (Week 12-14).	Total n=415 Participants Total of all reporting groups
Age, Continuous	62.2 years STANDARD_DEVIATION 8.38 • n=67 Participants	61.8 years STANDARD_DEVIATION 8.90 • n=67 Participants	60.9 years STANDARD_DEVIATION 9.57 • n=74 Participants	59.6 years STANDARD_DEVIATION 10.22 • n=68 Participants	61.2 years STANDARD_DEVIATION 9.95 • n=69 Participants	62.4 years STANDARD_DEVIATION 9.29 • n=70 Participants	61.3 years STANDARD_DEVIATION 9.40 • n=415 Participants
Sex: Female, Male Female	16 Participants n=67 Participants	11 Participants n=67 Participants	17 Participants n=74 Participants	13 Participants n=68 Participants	18 Participants n=69 Participants	14 Participants n=70 Participants	89 Participants n=415 Participants
Sex: Female, Male Male	51 Participants n=67 Participants	56 Participants n=67 Participants	57 Participants n=74 Participants	55 Participants n=68 Participants	51 Participants n=69 Participants	56 Participants n=70 Participants	326 Participants n=415 Participants
Region of Enrollment Japan	67 participants n=67 Participants	67 participants n=67 Participants	74 participants n=74 Participants	68 participants n=68 Participants	69 participants n=69 Participants	70 participants n=70 Participants	415 participants n=415 Participants
Body Mass Index (BMI)	25.93 kg/m^2 STANDARD_DEVIATION 4.024 • n=67 Participants • The analyzed numbers for each arm were participants who were evaluable for this baseline characteristic.	26.41 kg/m^2 STANDARD_DEVIATION 4.208 • n=67 Participants • The analyzed numbers for each arm were participants who were evaluable for this baseline characteristic.	26.91 kg/m^2 STANDARD_DEVIATION 5.035 • n=73 Participants • The analyzed numbers for each arm were participants who were evaluable for this baseline characteristic.	26.39 kg/m^2 STANDARD_DEVIATION 4.580 • n=68 Participants • The analyzed numbers for each arm were participants who were evaluable for this baseline characteristic.	26.41 kg/m^2 STANDARD_DEVIATION 3.543 • n=69 Participants • The analyzed numbers for each arm were participants who were evaluable for this baseline characteristic.	26.60 kg/m^2 STANDARD_DEVIATION 5.483 • n=70 Participants • The analyzed numbers for each arm were participants who were evaluable for this baseline characteristic.	26.45 kg/m^2 STANDARD_DEVIATION 4.518 • n=414 Participants • The analyzed numbers for each arm were participants who were evaluable for this baseline characteristic.
Duration of Type 2 Diabetes Mellitus	12.24 years STANDARD_DEVIATION 8.164 • n=67 Participants	11.48 years STANDARD_DEVIATION 7.355 • n=67 Participants	11.06 years STANDARD_DEVIATION 7.708 • n=74 Participants	11.19 years STANDARD_DEVIATION 7.151 • n=68 Participants	10.88 years STANDARD_DEVIATION 7.363 • n=69 Participants	10.38 years STANDARD_DEVIATION 7.046 • n=70 Participants	11.19 years STANDARD_DEVIATION 7.450 • n=415 Participants
Concurrent Medical Condition Hypertension - Yes	50 Participants n=67 Participants	46 Participants n=67 Participants	60 Participants n=74 Participants	48 Participants n=68 Participants	60 Participants n=69 Participants	52 Participants n=70 Participants	316 Participants n=415 Participants
Concurrent Medical Condition Hypertension - No	17 Participants n=67 Participants	21 Participants n=67 Participants	14 Participants n=74 Participants	20 Participants n=68 Participants	9 Participants n=69 Participants	18 Participants n=70 Participants	99 Participants n=415 Participants
Concurrent Medical Condition Dyslipidemia - Yes	45 Participants n=67 Participants	41 Participants n=67 Participants	58 Participants n=74 Participants	51 Participants n=68 Participants	56 Participants n=69 Participants	46 Participants n=70 Participants	297 Participants n=415 Participants
Concurrent Medical Condition Dyslipidemia - No	22 Participants n=67 Participants	26 Participants n=67 Participants	16 Participants n=74 Participants	17 Participants n=68 Participants	13 Participants n=69 Participants	24 Participants n=70 Participants	118 Participants n=415 Participants
Previous Medication Renin-angiotensin system (RAS) Inhibitor - Yes	30 Participants n=67 Participants	31 Participants n=67 Participants	33 Participants n=74 Participants	25 Participants n=68 Participants	36 Participants n=69 Participants	35 Participants n=70 Participants	190 Participants n=415 Participants
Previous Medication RAS Inhibitor - No	37 Participants n=67 Participants	36 Participants n=67 Participants	41 Participants n=74 Participants	43 Participants n=68 Participants	33 Participants n=69 Participants	35 Participants n=70 Participants	225 Participants n=415 Participants
Previous Medication Sodium Glucose Co-transporter (SGLT2)Inhibitor-Yes	1 Participants n=67 Participants	2 Participants n=67 Participants	3 Participants n=74 Participants	1 Participants n=68 Participants	2 Participants n=69 Participants	0 Participants n=70 Participants	9 Participants n=415 Participants
Previous Medication SGLT2 Inhibitor - No	66 Participants n=67 Participants	65 Participants n=67 Participants	71 Participants n=74 Participants	67 Participants n=68 Participants	67 Participants n=69 Participants	70 Participants n=70 Participants	406 Participants n=415 Participants
Previous Medication Potassium-Sparing Diuretic - Yes	0 Participants n=67 Participants	1 Participants n=67 Participants	0 Participants n=74 Participants	1 Participants n=68 Participants	0 Participants n=69 Participants	1 Participants n=70 Participants	3 Participants n=415 Participants
Previous Medication Potassium-Sparing Diuretic - No	67 Participants n=67 Participants	66 Participants n=67 Participants	74 Participants n=74 Participants	67 Participants n=68 Participants	69 Participants n=69 Participants	69 Participants n=70 Participants	412 Participants n=415 Participants
Restricted Medication Anti-Hypertension Drug - Yes	40 Participants n=67 Participants	34 Participants n=67 Participants	46 Participants n=74 Participants	33 Participants n=68 Participants	44 Participants n=69 Participants	45 Participants n=70 Participants	242 Participants n=415 Participants
Restricted Medication Anti-Hypertension Drug - No	27 Participants n=67 Participants	33 Participants n=67 Participants	28 Participants n=74 Participants	35 Participants n=68 Participants	25 Participants n=69 Participants	25 Participants n=70 Participants	173 Participants n=415 Participants
Restricted Medication Anti-Diabetic Drug - Yes	64 Participants n=67 Participants	64 Participants n=67 Participants	66 Participants n=74 Participants	65 Participants n=68 Participants	65 Participants n=69 Participants	66 Participants n=70 Participants	390 Participants n=415 Participants
Restricted Medication Anti-Diabetic Drug - No	3 Participants n=67 Participants	3 Participants n=67 Participants	8 Participants n=74 Participants	3 Participants n=68 Participants	4 Participants n=69 Participants	4 Participants n=70 Participants	25 Participants n=415 Participants
Restricted Medication HMG-CoA Reductase Inhibitor - Yes	30 Participants n=67 Participants	27 Participants n=67 Participants	35 Participants n=74 Participants	31 Participants n=68 Participants	44 Participants n=69 Participants	27 Participants n=70 Participants	194 Participants n=415 Participants
Restricted Medication HMG-CoA Reductase Inhibitor - No	37 Participants n=67 Participants	40 Participants n=67 Participants	39 Participants n=74 Participants	37 Participants n=68 Participants	25 Participants n=69 Participants	43 Participants n=70 Participants	221 Participants n=415 Participants
Urine albumin/Creatinine ratio	119.95 mg/gCR n=67 Participants • The analyzed numbers for each arm were participants who were evaluable for this baseline characteristic.	93.45 mg/gCR n=67 Participants • The analyzed numbers for each arm were participants who were evaluable for this baseline characteristic.	96.03 mg/gCR n=73 Participants • The analyzed numbers for each arm were participants who were evaluable for this baseline characteristic.	116.43 mg/gCR n=68 Participants • The analyzed numbers for each arm were participants who were evaluable for this baseline characteristic.	86.87 mg/gCR n=69 Participants • The analyzed numbers for each arm were participants who were evaluable for this baseline characteristic.	96.33 mg/gCR n=70 Participants • The analyzed numbers for each arm were participants who were evaluable for this baseline characteristic.	100.26 mg/gCR n=414 Participants • The analyzed numbers for each arm were participants who were evaluable for this baseline characteristic.
eGFRcreat	77.17 mL/min/1.73m^2 STANDARD_DEVIATION 18.828 • n=67 Participants • The analyzed numbers for each arm were participants who were evaluable for this baseline characteristic.	81.81 mL/min/1.73m^2 STANDARD_DEVIATION 19.788 • n=67 Participants • The analyzed numbers for each arm were participants who were evaluable for this baseline characteristic.	79.19 mL/min/1.73m^2 STANDARD_DEVIATION 19.449 • n=72 Participants • The analyzed numbers for each arm were participants who were evaluable for this baseline characteristic.	80.51 mL/min/1.73m^2 STANDARD_DEVIATION 20.292 • n=68 Participants • The analyzed numbers for each arm were participants who were evaluable for this baseline characteristic.	77.81 mL/min/1.73m^2 STANDARD_DEVIATION 18.425 • n=69 Participants • The analyzed numbers for each arm were participants who were evaluable for this baseline characteristic.	83.27 mL/min/1.73m^2 STANDARD_DEVIATION 22.777 • n=70 Participants • The analyzed numbers for each arm were participants who were evaluable for this baseline characteristic.	79.97 mL/min/1.73m^2 STANDARD_DEVIATION 19.980 • n=413 Participants • The analyzed numbers for each arm were participants who were evaluable for this baseline characteristic.
Haemoglobin A1c (HbA1c)	7.02 percentage of glycated haemoglobin STANDARD_DEVIATION 0.789 • n=67 Participants • The analyzed numbers for each arm were participants who were evaluable for this baseline characteristic.	7.03 percentage of glycated haemoglobin STANDARD_DEVIATION 0.772 • n=67 Participants • The analyzed numbers for each arm were participants who were evaluable for this baseline characteristic.	7.06 percentage of glycated haemoglobin STANDARD_DEVIATION 0.770 • n=73 Participants • The analyzed numbers for each arm were participants who were evaluable for this baseline characteristic.	7.03 percentage of glycated haemoglobin STANDARD_DEVIATION 0.789 • n=68 Participants • The analyzed numbers for each arm were participants who were evaluable for this baseline characteristic.	6.90 percentage of glycated haemoglobin STANDARD_DEVIATION 0.834 • n=69 Participants • The analyzed numbers for each arm were participants who were evaluable for this baseline characteristic.	7.02 percentage of glycated haemoglobin STANDARD_DEVIATION 0.731 • n=70 Participants • The analyzed numbers for each arm were participants who were evaluable for this baseline characteristic.	7.01 percentage of glycated haemoglobin STANDARD_DEVIATION 0.778 • n=414 Participants • The analyzed numbers for each arm were participants who were evaluable for this baseline characteristic.
Trough Sitting Diastolic Blood Pressure	80.6 mmHg STANDARD_DEVIATION 9.29 • n=67 Participants • The analyzed numbers for each arm were participants who were evaluable for this baseline characteristic.	80.6 mmHg STANDARD_DEVIATION 8.80 • n=67 Participants • The analyzed numbers for each arm were participants who were evaluable for this baseline characteristic.	80.6 mmHg STANDARD_DEVIATION 8.99 • n=73 Participants • The analyzed numbers for each arm were participants who were evaluable for this baseline characteristic.	79.3 mmHg STANDARD_DEVIATION 9.26 • n=68 Participants • The analyzed numbers for each arm were participants who were evaluable for this baseline characteristic.	81.9 mmHg STANDARD_DEVIATION 8.90 • n=69 Participants • The analyzed numbers for each arm were participants who were evaluable for this baseline characteristic.	80.5 mmHg STANDARD_DEVIATION 8.89 • n=70 Participants • The analyzed numbers for each arm were participants who were evaluable for this baseline characteristic.	80.6 mmHg STANDARD_DEVIATION 9.00 • n=414 Participants • The analyzed numbers for each arm were participants who were evaluable for this baseline characteristic.
Trough Sitting Systolic Blood Pressure	141.1 mmHg STANDARD_DEVIATION 7.01 • n=67 Participants • The analyzed numbers for each arm were participants who were evaluable for this baseline characteristic.	139.0 mmHg STANDARD_DEVIATION 8.41 • n=67 Participants • The analyzed numbers for each arm were participants who were evaluable for this baseline characteristic.	138.2 mmHg STANDARD_DEVIATION 7.09 • n=73 Participants • The analyzed numbers for each arm were participants who were evaluable for this baseline characteristic.	139.0 mmHg STANDARD_DEVIATION 7.64 • n=68 Participants • The analyzed numbers for each arm were participants who were evaluable for this baseline characteristic.	140.3 mmHg STANDARD_DEVIATION 7.77 • n=69 Participants • The analyzed numbers for each arm were participants who were evaluable for this baseline characteristic.	140.6 mmHg STANDARD_DEVIATION 7.65 • n=70 Participants • The analyzed numbers for each arm were participants who were evaluable for this baseline characteristic.	139.7 mmHg STANDARD_DEVIATION 7.63 • n=414 Participants • The analyzed numbers for each arm were participants who were evaluable for this baseline characteristic.

PRIMARY outcome

Timeframe: Week 0 and Week 12

Population: Full analysis set (FAS) included all participants who were randomized and received at least one dose of the study drug for the treatment period. Here number of participants analyzed are participants evaluable for this outcome measure.

Outcome measures

Outcome measures
Measure	Placebo n=66 Participants TAK-272 placebo, 4 tablets, and Candesartan cilexetil placebo one tablet, orally, once daily for up to 12 weeks. Participants were administered TAK-272 placebo 4 tablets and Candesartan cilexetil placebo one tablet for 4 weeks (Week -4 to 0) in placebo run-in period and follow-up period (Week 12-14).	TAK-272 5 mg n=67 Participants TAK-272 5 mg, one tablet, TAK-272 placebo 3 tablets, and Candesartan cilexetil placebo one tablet, orally, once daily for up to 12 weeks. Participants were administered TAK-272 placebo 4 tablets and Candesartan cilexetil placebo one tablet for 4 weeks (Week -4 to 0) in placebo run-in period and follow-up period (Week 12-14).	TAK-272 20 mg n=73 Participants TAK-272 20 mg, one tablet, TAK-272 placebo 3 tablets, and Candesartan cilexetil placebo one tablet, orally, once daily for up to 12 weeks. Participants were administered TAK-272 placebo 4 tablets and Candesartan cilexetil placebo one tablet for 4 weeks (Week -4 to 0) in placebo run-in period and follow-up period (Week 12-14).	TAK-272 40 mg n=67 Participants TAK-272 20 mg, 2 tablets, TAK-272 placebo 2 tablets, and Candesartan cilexetil placebo one tablet, orally, once daily for up to 12 weeks. Participants were administered TAK-272 placebo 4 tablets and Candesartan cilexetil placebo one tablet for 4 weeks (Week -4 to 0) in placebo run-in period and follow-up period (Week 12-14).	TAK-272 80 mg n=69 Participants TAK-272 20 mg, 4 tablets, and Candesartan cilexetil placebo one tablet, orally, once daily for up to 12 weeks. Participants were administered TAK-272 placebo 4 tablets and Candesartan cilexetil placebo one tablet for 4 weeks (Week -4 to 0) in placebo run-in period and follow-up period (Week 12-14).	Candesartan Cilexetil 8 mg n=70 Participants Candesartan cilexetil 8 mg, one tablet, and TAK-272 placebo 4 tablets, orally, once daily for up to 12 weeks. Participants were administered TAK-272 placebo 4 tablets and Candesartan cilexetil placebo one tablet for 4 weeks (Week -4 to 0) in placebo run-in period and follow-up period (Week 12-14).
Change From End of Pre-treatment Period (Week 0) in Log-transformed Urine Albumin/Creatinine Ratio (UACR) at the End of Treatment Period (Week 12)	0.152 log (mg/gCr) Interval 0.0389 to 0.2655	-0.173 log (mg/gCr) Interval -0.2848 to -0.0602	-0.317 log (mg/gCr) Interval -0.4245 to -0.2095	-0.478 log (mg/gCr) Interval -0.5904 to -0.3661	-0.497 log (mg/gCr) Interval -0.6081 to -0.3867	-0.377 log (mg/gCr) Interval -0.4872 to -0.2678

SECONDARY outcome

Timeframe: Weeks 2, 4, 8, 12, follow-up (Week 14) and End of Treatment

Population: The FAS included all participants who were randomized and received at least one dose of the study drug for the treatment period. The analyzed numbers for each arm were participants who were evaluable for this outcome measure at particular timepoint.

Outcome measures

Outcome measures
Measure	Placebo n=67 Participants TAK-272 placebo, 4 tablets, and Candesartan cilexetil placebo one tablet, orally, once daily for up to 12 weeks. Participants were administered TAK-272 placebo 4 tablets and Candesartan cilexetil placebo one tablet for 4 weeks (Week -4 to 0) in placebo run-in period and follow-up period (Week 12-14).	TAK-272 5 mg n=67 Participants TAK-272 5 mg, one tablet, TAK-272 placebo 3 tablets, and Candesartan cilexetil placebo one tablet, orally, once daily for up to 12 weeks. Participants were administered TAK-272 placebo 4 tablets and Candesartan cilexetil placebo one tablet for 4 weeks (Week -4 to 0) in placebo run-in period and follow-up period (Week 12-14).	TAK-272 20 mg n=74 Participants TAK-272 20 mg, one tablet, TAK-272 placebo 3 tablets, and Candesartan cilexetil placebo one tablet, orally, once daily for up to 12 weeks. Participants were administered TAK-272 placebo 4 tablets and Candesartan cilexetil placebo one tablet for 4 weeks (Week -4 to 0) in placebo run-in period and follow-up period (Week 12-14).	TAK-272 40 mg n=68 Participants TAK-272 20 mg, 2 tablets, TAK-272 placebo 2 tablets, and Candesartan cilexetil placebo one tablet, orally, once daily for up to 12 weeks. Participants were administered TAK-272 placebo 4 tablets and Candesartan cilexetil placebo one tablet for 4 weeks (Week -4 to 0) in placebo run-in period and follow-up period (Week 12-14).	TAK-272 80 mg n=69 Participants TAK-272 20 mg, 4 tablets, and Candesartan cilexetil placebo one tablet, orally, once daily for up to 12 weeks. Participants were administered TAK-272 placebo 4 tablets and Candesartan cilexetil placebo one tablet for 4 weeks (Week -4 to 0) in placebo run-in period and follow-up period (Week 12-14).	Candesartan Cilexetil 8 mg n=70 Participants Candesartan cilexetil 8 mg, one tablet, and TAK-272 placebo 4 tablets, orally, once daily for up to 12 weeks. Participants were administered TAK-272 placebo 4 tablets and Candesartan cilexetil placebo one tablet for 4 weeks (Week -4 to 0) in placebo run-in period and follow-up period (Week 12-14).
Urine Albumin/Creatinine Ratio (UACR) at Each Assessment Point Week 2	1.04 mg/gCr Interval 0.979 to 1.112	0.84 mg/gCr Interval 0.767 to 0.929	0.80 mg/gCr Interval 0.736 to 0.873	0.73 mg/gCr Interval 0.678 to 0.795	0.72 mg/gCr Interval 0.659 to 0.797	0.76 mg/gCr Interval 0.708 to 0.812
Urine Albumin/Creatinine Ratio (UACR) at Each Assessment Point Week 4	1.03 mg/gCr Interval 0.93 to 1.132	0.82 mg/gCr Interval 0.742 to 0.901	0.80 mg/gCr Interval 0.731 to 0.881	0.66 mg/gCr Interval 0.605 to 0.722	0.71 mg/gCr Interval 0.638 to 0.781	0.72 mg/gCr Interval 0.668 to 0.782
Urine Albumin/Creatinine Ratio (UACR) at Each Assessment Point Week 8	1.07 mg/gCr Interval 0.974 to 1.182	0.85 mg/gCr Interval 0.772 to 0.942	0.75 mg/gCr Interval 0.686 to 0.817	0.63 mg/gCr Interval 0.569 to 0.688	0.62 mg/gCr Interval 0.552 to 0.69	0.71 mg/gCr Interval 0.639 to 0.786
Urine Albumin/Creatinine Ratio (UACR) at Each Assessment Point Week 12	1.13 mg/gCr Interval 1.025 to 1.238	0.85 mg/gCr Interval 0.76 to 0.947	0.71 mg/gCr Interval 0.631 to 0.793	0.61 mg/gCr Interval 0.546 to 0.685	0.59 mg/gCr Interval 0.519 to 0.672	0.70 mg/gCr Interval 0.63 to 0.776
Urine Albumin/Creatinine Ratio (UACR) at Each Assessment Point Follow-up (Week 14)	1.11 mg/gCr Interval 0.985 to 1.255	0.92 mg/gCr Interval 0.83 to 1.031	0.95 mg/gCr Interval 0.861 to 1.055	0.80 mg/gCr Interval 0.725 to 0.872	0.86 mg/gCr Interval 0.77 to 0.966	0.85 mg/gCr Interval 0.771 to 0.936
Urine Albumin/Creatinine Ratio (UACR) at Each Assessment Point End of treatment	1.15 mg/gCr Interval 1.048 to 1.267	0.85 mg/gCr Interval 0.76 to 0.947	0.72 mg/gCr Interval 0.644 to 0.815	0.62 mg/gCr Interval 0.552 to 0.693	0.61 mg/gCr Interval 0.54 to 0.698	0.69 mg/gCr Interval 0.616 to 0.765

SECONDARY outcome

Timeframe: Week 12

Population: The FAS included all participants who were randomized and received at least one dose of the study drug for the treatment period. Here number of participants analyzed are participants evaluable for this outcome measure.

Remission rate is defined as percentage of participants who have UACR \<30 mg/gCr and whose UACR decreased by ≥30% from the value at the end of the pre-treatment period (Week 0).

Outcome measures

Outcome measures
Measure	Placebo n=66 Participants TAK-272 placebo, 4 tablets, and Candesartan cilexetil placebo one tablet, orally, once daily for up to 12 weeks. Participants were administered TAK-272 placebo 4 tablets and Candesartan cilexetil placebo one tablet for 4 weeks (Week -4 to 0) in placebo run-in period and follow-up period (Week 12-14).	TAK-272 5 mg n=67 Participants TAK-272 5 mg, one tablet, TAK-272 placebo 3 tablets, and Candesartan cilexetil placebo one tablet, orally, once daily for up to 12 weeks. Participants were administered TAK-272 placebo 4 tablets and Candesartan cilexetil placebo one tablet for 4 weeks (Week -4 to 0) in placebo run-in period and follow-up period (Week 12-14).	TAK-272 20 mg n=74 Participants TAK-272 20 mg, one tablet, TAK-272 placebo 3 tablets, and Candesartan cilexetil placebo one tablet, orally, once daily for up to 12 weeks. Participants were administered TAK-272 placebo 4 tablets and Candesartan cilexetil placebo one tablet for 4 weeks (Week -4 to 0) in placebo run-in period and follow-up period (Week 12-14).	TAK-272 40 mg n=67 Participants TAK-272 20 mg, 2 tablets, TAK-272 placebo 2 tablets, and Candesartan cilexetil placebo one tablet, orally, once daily for up to 12 weeks. Participants were administered TAK-272 placebo 4 tablets and Candesartan cilexetil placebo one tablet for 4 weeks (Week -4 to 0) in placebo run-in period and follow-up period (Week 12-14).	TAK-272 80 mg n=69 Participants TAK-272 20 mg, 4 tablets, and Candesartan cilexetil placebo one tablet, orally, once daily for up to 12 weeks. Participants were administered TAK-272 placebo 4 tablets and Candesartan cilexetil placebo one tablet for 4 weeks (Week -4 to 0) in placebo run-in period and follow-up period (Week 12-14).	Candesartan Cilexetil 8 mg n=70 Participants Candesartan cilexetil 8 mg, one tablet, and TAK-272 placebo 4 tablets, orally, once daily for up to 12 weeks. Participants were administered TAK-272 placebo 4 tablets and Candesartan cilexetil placebo one tablet for 4 weeks (Week -4 to 0) in placebo run-in period and follow-up period (Week 12-14).
Remission Rate From Early-Stage Nephropathy (Stage 2) to Pre-Nephropathy Stage (Stage 1) at the End of Treatment (Week 12)	0.0 percentage of participants Interval 0.0 to 5.436	9.0 percentage of participants Interval 3.358 to 18.48	9.5 percentage of participants Interval 3.888 to 18.524	17.9 percentage of participants Interval 9.612 to 29.196	24.6 percentage of participants Interval 15.055 to 36.49	14.3 percentage of participants Interval 7.069 to 24.707

SECONDARY outcome

Timeframe: Week 12

Progression rate is defined as percentage of participants who have UACR ≥300 mg/gCr and whose UACR increased by ≥30% from the value at the end of the pre-treatment period \[Week 0\]. Meanwhile, the definition of transition to overt nephropathy also includes the case that UACR decreased to \<300 mg/gCr after the transition to overt nephropathy.

Outcome measures

Outcome measures
Measure	Placebo n=66 Participants TAK-272 placebo, 4 tablets, and Candesartan cilexetil placebo one tablet, orally, once daily for up to 12 weeks. Participants were administered TAK-272 placebo 4 tablets and Candesartan cilexetil placebo one tablet for 4 weeks (Week -4 to 0) in placebo run-in period and follow-up period (Week 12-14).	TAK-272 5 mg n=67 Participants TAK-272 5 mg, one tablet, TAK-272 placebo 3 tablets, and Candesartan cilexetil placebo one tablet, orally, once daily for up to 12 weeks. Participants were administered TAK-272 placebo 4 tablets and Candesartan cilexetil placebo one tablet for 4 weeks (Week -4 to 0) in placebo run-in period and follow-up period (Week 12-14).	TAK-272 20 mg n=74 Participants TAK-272 20 mg, one tablet, TAK-272 placebo 3 tablets, and Candesartan cilexetil placebo one tablet, orally, once daily for up to 12 weeks. Participants were administered TAK-272 placebo 4 tablets and Candesartan cilexetil placebo one tablet for 4 weeks (Week -4 to 0) in placebo run-in period and follow-up period (Week 12-14).	TAK-272 40 mg n=67 Participants TAK-272 20 mg, 2 tablets, TAK-272 placebo 2 tablets, and Candesartan cilexetil placebo one tablet, orally, once daily for up to 12 weeks. Participants were administered TAK-272 placebo 4 tablets and Candesartan cilexetil placebo one tablet for 4 weeks (Week -4 to 0) in placebo run-in period and follow-up period (Week 12-14).	TAK-272 80 mg n=69 Participants TAK-272 20 mg, 4 tablets, and Candesartan cilexetil placebo one tablet, orally, once daily for up to 12 weeks. Participants were administered TAK-272 placebo 4 tablets and Candesartan cilexetil placebo one tablet for 4 weeks (Week -4 to 0) in placebo run-in period and follow-up period (Week 12-14).	Candesartan Cilexetil 8 mg n=70 Participants Candesartan cilexetil 8 mg, one tablet, and TAK-272 placebo 4 tablets, orally, once daily for up to 12 weeks. Participants were administered TAK-272 placebo 4 tablets and Candesartan cilexetil placebo one tablet for 4 weeks (Week -4 to 0) in placebo run-in period and follow-up period (Week 12-14).
Progression Rate From Early-Stage Nephropathy (Stage 2) to Overt Nephropathy (Stage 3) During the Treatment Period (Week 12)	18.2 percentage of participants Interval 9.764 to 29.607	3.0 percentage of participants Interval 0.364 to 10.371	0.0 percentage of participants Interval 0.0 to 4.863	0.0 percentage of participants Interval 0.0 to 5.357	0.0 percentage of participants Interval 0.0 to 5.206	1.4 percentage of participants Interval 0.036 to 7.704

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to Week 14

Population: Safety analysis set included all participants who received at least one dose of the study drug for the treatment period.

An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. A treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug.

Outcome measures

Outcome measures
Measure	Placebo n=67 Participants TAK-272 placebo, 4 tablets, and Candesartan cilexetil placebo one tablet, orally, once daily for up to 12 weeks. Participants were administered TAK-272 placebo 4 tablets and Candesartan cilexetil placebo one tablet for 4 weeks (Week -4 to 0) in placebo run-in period and follow-up period (Week 12-14).	TAK-272 5 mg n=67 Participants TAK-272 5 mg, one tablet, TAK-272 placebo 3 tablets, and Candesartan cilexetil placebo one tablet, orally, once daily for up to 12 weeks. Participants were administered TAK-272 placebo 4 tablets and Candesartan cilexetil placebo one tablet for 4 weeks (Week -4 to 0) in placebo run-in period and follow-up period (Week 12-14).	TAK-272 20 mg n=74 Participants TAK-272 20 mg, one tablet, TAK-272 placebo 3 tablets, and Candesartan cilexetil placebo one tablet, orally, once daily for up to 12 weeks. Participants were administered TAK-272 placebo 4 tablets and Candesartan cilexetil placebo one tablet for 4 weeks (Week -4 to 0) in placebo run-in period and follow-up period (Week 12-14).	TAK-272 40 mg n=68 Participants TAK-272 20 mg, 2 tablets, TAK-272 placebo 2 tablets, and Candesartan cilexetil placebo one tablet, orally, once daily for up to 12 weeks. Participants were administered TAK-272 placebo 4 tablets and Candesartan cilexetil placebo one tablet for 4 weeks (Week -4 to 0) in placebo run-in period and follow-up period (Week 12-14).	TAK-272 80 mg n=69 Participants TAK-272 20 mg, 4 tablets, and Candesartan cilexetil placebo one tablet, orally, once daily for up to 12 weeks. Participants were administered TAK-272 placebo 4 tablets and Candesartan cilexetil placebo one tablet for 4 weeks (Week -4 to 0) in placebo run-in period and follow-up period (Week 12-14).	Candesartan Cilexetil 8 mg n=70 Participants Candesartan cilexetil 8 mg, one tablet, and TAK-272 placebo 4 tablets, orally, once daily for up to 12 weeks. Participants were administered TAK-272 placebo 4 tablets and Candesartan cilexetil placebo one tablet for 4 weeks (Week -4 to 0) in placebo run-in period and follow-up period (Week 12-14).
Number of Participants Who Experience at Least One Treatment Emergent Adverse Event (TEAE)	28 Participants	22 Participants	26 Participants	28 Participants	36 Participants	30 Participants

Adverse Events

Placebo

Serious events: 2 serious events

Other events: 7 other events

Deaths: 0 deaths

TAK-272 5 mg

Serious events: 0 serious events

Other events: 7 other events

Deaths: 0 deaths

TAK-272 20 mg

Serious events: 0 serious events

Other events: 8 other events

Deaths: 0 deaths

TAK-272 40 mg

Serious events: 0 serious events

Other events: 9 other events

Deaths: 0 deaths

TAK-272 80 mg

Serious events: 2 serious events

Other events: 11 other events

Deaths: 0 deaths

Candesartan Cilexetil 8 mg

Serious events: 1 serious events

Other events: 11 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Placebo n=67 participants at risk TAK-272 placebo, 4 tablets, and Candesartan cilexetil placebo one tablet, orally, once daily for up to 12 weeks. Participants were administered TAK-272 placebo 4 tablets and Candesartan cilexetil placebo one tablet for 4 weeks (Week -4 to 0) in placebo run-in period and follow-up period (Week 12-14).	TAK-272 5 mg n=67 participants at risk TAK-272 5 mg, one tablet, TAK-272 placebo 3 tablets, and Candesartan cilexetil placebo one tablet, orally, once daily for up to 12 weeks. Participants were administered TAK-272 placebo 4 tablets and Candesartan cilexetil placebo one tablet for 4 weeks (Week -4 to 0) in placebo run-in period and follow-up period (Week 12-14).	TAK-272 20 mg n=74 participants at risk TAK-272 20 mg, one tablet, TAK-272 placebo 3 tablets, and Candesartan cilexetil placebo one tablet, orally, once daily for up to 12 weeks. Participants were administered TAK-272 placebo 4 tablets and Candesartan cilexetil placebo one tablet for 4 weeks (Week -4 to 0) in placebo run-in period and follow-up period (Week 12-14).	TAK-272 40 mg n=68 participants at risk TAK-272 20 mg, 2 tablets, TAK-272 placebo 2 tablets, and Candesartan cilexetil placebo one tablet, orally, once daily for up to 12 weeks. Participants were administered TAK-272 placebo 4 tablets and Candesartan cilexetil placebo one tablet for 4 weeks (Week -4 to 0) in placebo run-in period and follow-up period (Week 12-14).	TAK-272 80 mg n=69 participants at risk TAK-272 20 mg, 4 tablets, and Candesartan cilexetil placebo one tablet, orally, once daily for up to 12 weeks. Participants were administered TAK-272 placebo 4 tablets and Candesartan cilexetil placebo one tablet for 4 weeks (Week -4 to 0) in placebo run-in period and follow-up period (Week 12-14).	Candesartan Cilexetil 8 mg n=70 participants at risk Candesartan cilexetil 8 mg, one tablet, and TAK-272 placebo 4 tablets, orally, once daily for up to 12 weeks. Participants were administered TAK-272 placebo 4 tablets and Candesartan cilexetil placebo one tablet for 4 weeks (Week -4 to 0) in placebo run-in period and follow-up period (Week 12-14).
Gastrointestinal disorders Diverticulum intestinal haemorrhagic	0.00% 0/67 • Up to Week 14 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/67 • Up to Week 14 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/74 • Up to Week 14 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/68 • Up to Week 14 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	1.4% 1/69 • Up to Week 14 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/70 • Up to Week 14 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Adenocarcinoma gastric	1.5% 1/67 • Up to Week 14 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/67 • Up to Week 14 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/74 • Up to Week 14 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/68 • Up to Week 14 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/69 • Up to Week 14 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/70 • Up to Week 14 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Hepatocellular carcinoma	1.5% 1/67 • Up to Week 14 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/67 • Up to Week 14 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/74 • Up to Week 14 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/68 • Up to Week 14 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/69 • Up to Week 14 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/70 • Up to Week 14 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Prostate cancer	0.00% 0/67 • Up to Week 14 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/67 • Up to Week 14 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/74 • Up to Week 14 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/68 • Up to Week 14 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	1.4% 1/69 • Up to Week 14 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/70 • Up to Week 14 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Nervous system disorders Cerebral infarction	0.00% 0/67 • Up to Week 14 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/67 • Up to Week 14 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/74 • Up to Week 14 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/68 • Up to Week 14 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/69 • Up to Week 14 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	1.4% 1/70 • Up to Week 14 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.

Other adverse events

Other adverse events
Measure	Placebo n=67 participants at risk TAK-272 placebo, 4 tablets, and Candesartan cilexetil placebo one tablet, orally, once daily for up to 12 weeks. Participants were administered TAK-272 placebo 4 tablets and Candesartan cilexetil placebo one tablet for 4 weeks (Week -4 to 0) in placebo run-in period and follow-up period (Week 12-14).	TAK-272 5 mg n=67 participants at risk TAK-272 5 mg, one tablet, TAK-272 placebo 3 tablets, and Candesartan cilexetil placebo one tablet, orally, once daily for up to 12 weeks. Participants were administered TAK-272 placebo 4 tablets and Candesartan cilexetil placebo one tablet for 4 weeks (Week -4 to 0) in placebo run-in period and follow-up period (Week 12-14).	TAK-272 20 mg n=74 participants at risk TAK-272 20 mg, one tablet, TAK-272 placebo 3 tablets, and Candesartan cilexetil placebo one tablet, orally, once daily for up to 12 weeks. Participants were administered TAK-272 placebo 4 tablets and Candesartan cilexetil placebo one tablet for 4 weeks (Week -4 to 0) in placebo run-in period and follow-up period (Week 12-14).	TAK-272 40 mg n=68 participants at risk TAK-272 20 mg, 2 tablets, TAK-272 placebo 2 tablets, and Candesartan cilexetil placebo one tablet, orally, once daily for up to 12 weeks. Participants were administered TAK-272 placebo 4 tablets and Candesartan cilexetil placebo one tablet for 4 weeks (Week -4 to 0) in placebo run-in period and follow-up period (Week 12-14).	TAK-272 80 mg n=69 participants at risk TAK-272 20 mg, 4 tablets, and Candesartan cilexetil placebo one tablet, orally, once daily for up to 12 weeks. Participants were administered TAK-272 placebo 4 tablets and Candesartan cilexetil placebo one tablet for 4 weeks (Week -4 to 0) in placebo run-in period and follow-up period (Week 12-14).	Candesartan Cilexetil 8 mg n=70 participants at risk Candesartan cilexetil 8 mg, one tablet, and TAK-272 placebo 4 tablets, orally, once daily for up to 12 weeks. Participants were administered TAK-272 placebo 4 tablets and Candesartan cilexetil placebo one tablet for 4 weeks (Week -4 to 0) in placebo run-in period and follow-up period (Week 12-14).
Infections and infestations Nasopharyngitis	10.4% 7/67 • Up to Week 14 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	10.4% 7/67 • Up to Week 14 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	10.8% 8/74 • Up to Week 14 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	13.2% 9/68 • Up to Week 14 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	15.9% 11/69 • Up to Week 14 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	15.7% 11/70 • Up to Week 14 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.

Additional Information

Medical Director

Takeda

Phone: +1-877-825-3327

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The first study related publication will be a multi-center publication submitted within 24 months after conclusion or termination of a study at all sites. After such multi site publication, all proposed site publications and presentations will be submitted to sponsor for review 60 days in advance of publication. Site will remove Sponsor confidential information unrelated to study results. Sponsor can delay a proposed publication for another 60 days to preserve intellectual property.
Publication restrictions are in place

Restriction type: OTHER