A Phase 2 Dose-finding Study of TAK-272 in Participants With Type 2 Diabetes Mellitus and Microalbuminuria

Exclusion Criteria

• •The participant received TAK-272 in a previous clinical study.
• •The participant is an immediate family member, study site employee, or is in a dependent relationship with a study site employee who is involved in the conduct of this study (e.g., spouse, parent, child, sibling) or may consent to participate under duress.
• •The participant has a history of hypersensitivity or allergies to TAK-272, candesartan cilexetil and other renin-angiotensin system (RAS) inhibitors (angiotensin converting enzyme \[ACE\] inhibitors, angiotensin II receptor blocker \[ARBs\] or direct renin inhibitor \[DRIs\]).
• •The participant needs to take the prohibited medications during the study period.
• •The participant has hyperkalemia (e.g., serum potassium ≥ 5.0 mEq/L at the start of the pretreatment period (Week -8) and Week -4 or requiring regular use of a potassium adsorbent) or onset of hyperkalemia within 2 years prior to starting the pre-treatment period.
• •The participant has at least class II hypertension (e.g., sitting systolic blood pressure \[SBP\] ≥160 mmHg or sitting diastolic blood pressure \[DBP\] ≥100 mmHg in the pre-treatment period) or malignant hypertension.
• •The participant has a renal disease other than type 2 diabetic nephropathy (e.g., patients with renal sclerosis, acute or chronic glomerular nephritis, or polycystic kidney).
• •The participant has bilateral or unilateral renal artery stenosis.
• •The participant requires regular use of nonsteroidal anti-inflammatory drugs (excluding low-dose aspirin and locally-acting agents such as topical drugs) (e.g., rheumatoid arthritis patients, osteoarthritis patients, and low back pain patients).
• •The participant has a history of any of the cardiovascular diseases listed below within 2 years prior to starting the pre-treatment period:
• •* Cardiac diseases: myocardial infarction, coronary arterial revascularization
• •* Cerebrovascular diseases: cerebral infarction (excluding lacunar infarction), cerebral hemorrhage, transient ischemic attack
• •The participant has any of the cardiovascular diseases listed below:
• •* Cardiac diseases: angina pectoris, arrhythmia, and congested heart failure that requires medication
• •* Vascular diseases: arteriosclerosis obliterans with symptoms (e.g., intermittent claudication)
• •The participant has a clinically significant hepatic disorder (e.g., either of alanine aminotransferase \[ALT\] or aspartate aminotransferase \[AST\] is ≥ 2.5 times the upper limit of normal at the start of the pre-treatment period (Week -8) or at Week -4).
• •The participant has a complication of malignant tumor.
• •If female, the participant is pregnant, lactating, or is intending to become pregnant before, during or within 1 month after participating in this study; or intending to donate ova during such time period.
• •If male, the participant intends to donate sperm during the course of this study or for 12 weeks thereafter.
• •The participant is judged by the investigator or the sub-investigator as being ineligible for any other reason.
• •The participant has participated in another clinical study or post-marketing study within 30 days prior to starting the pre-treatment period.
• •The participant has received the study medication within 12 weeks prior to starting the pre-treatment period.
• •The participant has a history of drug abuse (defined as the use of an illicit drug) or history of alcohol abuse within 2 years prior to starting the pre-treatment period.
• •The participant has changed the renin angiotensin system (RAS) inhibitor (angiotensin-converting enzyme \[ACE\] inhibitor, angiotensin II receptor blocker \[ARB\] or direct renin inhibitors \[DRI\]) or its dose and regimen within 12 weeks prior to starting the pre-treatment period.
• •The participant is treated with any RAS inhibitor (ACE inhibitor, ARB or DRI) at signing of informed consent, and whose UACR is \<30 mg/gCr at the start of the pre-treatment period (Week -8).
• •The participant has hemoglobin A1c (HbA1c) (National Glycohemoglobin Standardization Program \[NGSP\]) ≥9.0% at Week -4.
• •The participant has change in HbA1c (NGSP) from the start of the pre-treatment period (Week -8) to Week -4 by ≥10.0%\* compared to the higher value of them.
• •The participant's sitting SBP and sitting DBP changed by ≥20 mmHg or ≥10 mmHg, respectively, at the end of the pre-treatment period (Week 0) compared to Week -2.
• •The participant's sitting SBP is \<130 mmHg at the end of the pre-treatment period (Week 0).
• •The participant's study drug compliance rate\* during the pre-treatment period is \<80.0%.
• •* Compliance rate (%)=(Prescribed amount-Retrieved amount)/ {(Completion date of study drug for the pre-treatment period-Starting date of study drug for the pre-treatment period+1)×5}×100, second decimal place to be rounded off.