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

NCT02332824 | Completed Phase 2 Results

• 3 other identifiers: TAK-272/CCT-101JapicCTI-142658U1111-1161-6858
• Study Type: interventional
• Target: 415
• Locations: 1 country
• Sites: 68

Brief Summary

The purpose of this study is to test the efficacy and safety on daily oral doses of TAK-272 5 mg, 20 mg, 40 mg and 80 mg in patients with type 2 diabetes mellitus and microalbuminuria by randomized, double-blind, placebo-controlled, parallel-group comparison in order to determine the clinical dose of TAK-272.

Conditions

Type 2 Diabetes Mellitus and Microalbuminuria

Keywords

Pharmacological therapy

Outcome Measures

Primary Outcomes (1)

• 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)

  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.

  Week 0 and Week 12

Secondary Outcomes (3)

• Urine Albumin/Creatinine Ratio (UACR) at Each Assessment Point

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

• Remission Rate From Early-Stage Nephropathy (Stage 2) to Pre-Nephropathy Stage (Stage 1) at the End of Treatment (Week 12)

  Week 12

• Progression Rate From Early-Stage Nephropathy (Stage 2) to Overt Nephropathy (Stage 3) During the Treatment Period (Week 12)

  Week 12

Other Outcomes (1)

• Number of Participants Who Experience at Least One Treatment Emergent Adverse Event (TEAE)

  Up to Week 14

Study Arms (6)

Placebo

PLACEBO COMPARATOR

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).

Drug: TAK-272 Placebo; Drug: Candesartan cilexetil Placebo

TAK-272 5 mg

EXPERIMENTAL

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).

Drug: TAK-272; Drug: TAK-272 Placebo; Drug: Candesartan cilexetil Placebo

TAK-272 20 mg

EXPERIMENTAL

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).

Drug: TAK-272; Drug: TAK-272 Placebo; Drug: Candesartan cilexetil Placebo

TAK-272 40 mg

EXPERIMENTAL

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).

Drug: TAK-272; Drug: TAK-272 Placebo; Drug: Candesartan cilexetil Placebo

TAK-272 80 mg

EXPERIMENTAL

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).

Drug: TAK-272; Drug: Candesartan cilexetil Placebo

Candesartan cilexetil 8 mg

ACTIVE COMPARATOR

TAK-272 placebo 4 tablets and Candesartan cilexetil 8 mg 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).

Drug: TAK-272 Placebo; Drug: Candesartan cilexetil

Interventions

TAK-272 DRUG

TAK-272 tablets

TAK-272 20 mg; TAK-272 40 mg; TAK-272 5 mg; TAK-272 80 mg

TAK-272 Placebo DRUG

TAK-272 placebo-matching tablets

Candesartan cilexetil 8 mg; Placebo; TAK-272 20 mg; TAK-272 40 mg; TAK-272 5 mg

Candesartan cilexetil DRUG

Candesartan cilexetil tablets

Candesartan cilexetil 8 mg

Candesartan cilexetil Placebo DRUG

Candesartan cilexetil placebo-matching tablets

Placebo; TAK-272 20 mg; TAK-272 40 mg; TAK-272 5 mg; TAK-272 80 mg

Eligibility Criteria

• Age: 20 Years - 74 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• In the opinion of the investigator or the sub-investigator, the participant is capable of understanding and complying with protocol requirements.
• The participant signs and dates a written, informed consent form prior to the initiation of any study procedures.
• The participant is either male or female and aged 20 to less than 75 years at signing of informed consent.
• The participant is an early-stage nephropathy (Stage 2) patient with type 2 diabetes mellitus.
• Inpatient/outpatient: outpatient
• The participant is a patient with type 2 diabetes mellitus on a certain diet therapy and/or exercise therapy (if any).
• The participant has stability controlled blood glucose, blood pressure and lipid, and does not need any change in the drug and the dose of any antihypertensive, antidiabetic and antidyslipidemia or antihyperlipidemic drugs throughout the study period as judged by the investigator or the sub-investigator.
• The participant has urine albumin/creatinine ratio (UACR) of the first morning urine (the first urine immediately after rising prior to activities in standing position in the morning) is ≥30 to \<300 mg/gCr on at least two of three measurements at the start of the pre-treatment period (Week -8), at Week -4 or Week -2.
• The participant has estimated glomerular filtration rate according to creatinine (eGFRcreat) ≥45 mL/min/1.73 m\^2 at Week -4.
• A male participant who is nonsterilized and sexually active with a female partner of childbearing potential agrees to use adequate contraception from signing of informed consent throughout the study period and for 12 weeks after the completion of the study.
• A female participant of childbearing potential who is sexually active with a nonsterilized male partner who agrees to routinely use adequate contraception from signing of informed consent until 1 month after the completion of the study.

You may not qualify if:

• 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)

Sponsors & Collaborators

• Takeda: lead

Study Sites (68)

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Nagoya, Aichi-ken, Japan

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Chiba, Chiba, Japan

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Kisarazu-shi, Chiba, Japan

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Fukuoka, Fukuoka, Japan

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Fukutsu-shi, Fukuoka, Japan

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Kitakyuushu-shi, Fukuoka, Japan

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Kouriyama-shi, Fukushima, Japan

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Anchu-shi, Gunma, Japan

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Ota-shi, Gunma, Japan

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Ishikari-shi, Hokkaido, Japan

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Obihiro-shi, Hokkaido, Japan

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Sapporo, Hokkaido, Japan

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Kobe, Hyōgo, Japan

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Nishinomiya-shi, Hyōgo, Japan

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Moriya-shi, Ibaragi, Japan

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Naka, Ibaragi, Japan

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Koga, Ibarakgi, Japan

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Koga-shi, Ibaraki, Japan

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Mito, Ibaraki, Japan

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Takamatsu, Kagawa-ken, Japan

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Ebina-shi, Kanagawa, Japan

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Hiratsuka-shi, Kanagawa, Japan

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Kawasaki-shi, Kanagawa, Japan

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Miura-shi, Kanagawa, Japan

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Shounann-shi, Kanagawa, Japan

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Yokohama, Kanagawa, Japan

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Kochi, Kochi, Japan

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Kumamoto, Kumamoto, Japan

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Yatsushiro-shi, Kumamoto, Japan

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Kyoto, Kyoto, Japan

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Uji-shi, Kyoto, Japan

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Sendai, Miyagi, Japan

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Miyazaki, Miyazaki, Japan

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Azumino-shi, Nagano, Japan

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Matsumoto-shi, Nagano, Japan

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Nakano-shi, Nagano, Japan

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Sasebo-shi, Nagasaki, Japan

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Kasaoka-shi, Okayama-ken, Japan

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Kurashiki-shi, Okayama-ken, Japan

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Naha, Okinawa, Japan

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Shimajiri-gun, Okinawa, Japan

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Tomigusuku-shi, Okinawa, Japan

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Kashiwara-shi, Osaka, Japan

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Matsubara-shi, Osaka, Japan

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Neyagawa, Osaka, Japan

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Osaka, Osaka, Japan

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Suita-shi, Osaka, Japan

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Tondabayashi-shi, Osaka, Japan

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Kawagoe-shi, Saitama, Japan

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Kyuki-shi, Saitama, Japan

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Saitama-shi, Saitama, Japan

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Hamamatsu, Shizuoka, Japan

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Shizuoka, Shizuoka, Japan

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Koyama-shi, Tochigi, Japan

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Shimono-shi, Tochigi, Japan

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Chiyoda-ku, Tokyo, Japan

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Chuo-ku, Tokyo, Japan

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Hachioji-shi, Tokyo, Japan

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Hino-shi, Tokyo, Japan

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Itabashi-ku, Tokyo, Japan

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Katsushika-ku, Tokyo, Japan

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Nerima-ku, Tokyo, Japan

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Ōta-ku, Tokyo, Japan

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Shibuya-ku, Tokyo, Japan

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Shinagawa-ku, Tokyo, Japan

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Shinjuku-ku, Tokyo, Japan

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Shinjyuku-ku, Tokyo, Japan

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Ube-shi, Yamaguchi, Japan

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Related Publications (1)

• Wang GM, Li LJ, Fan L, Xu M, Tang WL, Wright JM. Renin inhibitors versus angiotensin receptor blockers for primary hypertension. Cochrane Database Syst Rev. 2025 Feb 27;2(2):CD012570. doi: 10.1002/14651858.CD012570.pub2.

  PMID: 40013543 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

imarikiren hydrochloride; candesartan cilexetil

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Results Point of Contact

• Title: Medical Director
• Organization: Takeda

trialdisclosures@takeda.com

+1-877-825-3327

Study Officials

• Medical Director Clinical Science

  Takeda

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 26, 2014
• First Posted: January 7, 2015
• Study Start: October 16, 2014
• Primary Completion: August 18, 2016
• Study Completion: August 18, 2016
• Last Updated: August 13, 2018
• Results First Posted: August 13, 2018

Record last verified: 2017-11

Locations

JP (68)