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NCT02332824

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

Completed Phase 2 Results posted Last updated 13 August 2018
What this trial tests

Phase 2 trial testing TAK-272 in Type 2 Diabetes Mellitus and Microalbuminuria in 415 participants. Completed in 18 August 2016.

Timeline
16 October 2014
Primary endpoint
18 August 2016
18 August 2016

Quick facts

Lead sponsorTakeda
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingquadruple
Primary purposetreatment
Enrollment415
Start date16 October 2014
Primary completion18 August 2016
Estimated completion18 August 2016
Sites68 locations across Japan

Drugs / interventions tested

Conditions studied

Sponsor

Takeda — full company profile →

Who can join

Adults 20 to 74, any sex, with Type 2 Diabetes Mellitus and Microalbuminuria. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

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) Primary · Week 0 and 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.

GroupValue95% CI
Placebo0.1520.0389 – 0.2655
TAK-272 5 mg-0.173-0.2848 – -0.0602
TAK-272 20 mg-0.317-0.4245 – -0.2095
TAK-272 40 mg-0.478-0.5904 – -0.3661
TAK-272 80 mg-0.497-0.6081 – -0.3867
Candesartan Cilexetil 8 mg-0.377-0.4872 – -0.2678
Urine Albumin/Creatinine Ratio (UACR) at Each Assessment Point Secondary · Weeks 2, 4, 8, 12, follow-up (Week 14) and End of Treatment

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. Reported data is geometric mean ratio of UACR at each assessment point relative to Baseline.

Week 2
GroupValue95% CI
Placebo1.040.979 – 1.112
TAK-272 5 mg0.840.767 – 0.929
TAK-272 20 mg0.800.736 – 0.873
TAK-272 40 mg0.730.678 – 0.795
TAK-272 80 mg0.720.659 – 0.797
Candesartan Cilexetil 8 mg0.760.708 – 0.812
Week 4
GroupValue95% CI
Placebo1.030.930 – 1.132
TAK-272 5 mg0.820.742 – 0.901
TAK-272 20 mg0.800.731 – 0.881
TAK-272 40 mg0.660.605 – 0.722
TAK-272 80 mg0.710.638 – 0.781
Candesartan Cilexetil 8 mg0.720.668 – 0.782
Week 8
GroupValue95% CI
Placebo1.070.974 – 1.182
TAK-272 5 mg0.850.772 – 0.942
TAK-272 20 mg0.750.686 – 0.817
TAK-272 40 mg0.630.569 – 0.688
TAK-272 80 mg0.620.552 – 0.690
Candesartan Cilexetil 8 mg0.710.639 – 0.786
Week 12
GroupValue95% CI
Placebo1.131.025 – 1.238
TAK-272 5 mg0.850.760 – 0.947
TAK-272 20 mg0.710.631 – 0.793
TAK-272 40 mg0.610.546 – 0.685
TAK-272 80 mg0.590.519 – 0.672
Candesartan Cilexetil 8 mg0.700.630 – 0.776
Follow-up (Week 14)
GroupValue95% CI
Placebo1.110.985 – 1.255
TAK-272 5 mg0.920.830 – 1.031
TAK-272 20 mg0.950.861 – 1.055
TAK-272 40 mg0.800.725 – 0.872
TAK-272 80 mg0.860.770 – 0.966
Candesartan Cilexetil 8 mg0.850.771 – 0.936
End of treatment
GroupValue95% CI
Placebo1.151.048 – 1.267
TAK-272 5 mg0.850.760 – 0.947
TAK-272 20 mg0.720.644 – 0.815
TAK-272 40 mg0.620.552 – 0.693
TAK-272 80 mg0.610.540 – 0.698
Candesartan Cilexetil 8 mg0.690.616 – 0.765
Remission Rate From Early-Stage Nephropathy (Stage 2) to Pre-Nephropathy Stage (Stage 1) at the End of Treatment (Week 12) Secondary · Week 12

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).

GroupValue95% CI
Placebo0.00.000 – 5.436
TAK-272 5 mg9.03.358 – 18.480
TAK-272 20 mg9.53.888 – 18.524
TAK-272 40 mg17.99.612 – 29.196
TAK-272 80 mg24.615.055 – 36.490
Candesartan Cilexetil 8 mg14.37.069 – 24.707
Progression Rate From Early-Stage Nephropathy (Stage 2) to Overt Nephropathy (Stage 3) During the Treatment Period (Week 12) Secondary · 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.

GroupValue95% CI
Placebo18.29.764 – 29.607
TAK-272 5 mg3.00.364 – 10.371
TAK-272 20 mg0.00.000 – 4.863
TAK-272 40 mg0.00.000 – 5.357
TAK-272 80 mg0.00.000 – 5.206
Candesartan Cilexetil 8 mg1.40.036 – 7.704
Number of Participants Who Experience at Least One Treatment Emergent Adverse Event (TEAE) Secondary · Up to Week 14

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.

GroupValue95% CI
Placebo28
TAK-272 5 mg22
TAK-272 20 mg26
TAK-272 40 mg28
TAK-272 80 mg36
Candesartan Cilexetil 8 mg30

Adverse events — posted to ClinicalTrials.gov

Time frame: Up to Week 14. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Placebo
Serious: 2/67 (3%)
Deaths:
TAK-272 5 mg
Serious: 0/67 (0%)
Deaths:
TAK-272 20 mg
Serious: 0/74 (0%)
Deaths:
TAK-272 40 mg
Serious: 0/68 (0%)
Deaths:
TAK-272 80 mg
Serious: 2/69 (3%)
Deaths:
Candesartan Cilexetil 8 mg
Serious: 1/70 (1%)
Deaths:

Serious adverse events (5 terms)

ReactionSystemPlaceboTAK-272 5 mgTAK-272 20 mgTAK-272 40 mgTAK-272 80 mgCandesartan Cilexetil 8 mg
Diverticulum intestinal haemorrhagicGastrointestinal disorders
Adenocarcinoma gastricNeoplasms benign, malignant and unspecified (incl cysts and polyps)
Hepatocellular carcinomaNeoplasms benign, malignant and unspecified (incl cysts and polyps)
Prostate cancerNeoplasms benign, malignant and unspecified (incl cysts and polyps)
Cerebral infarctionNervous system disorders
Other adverse events (1 terms — click to expand)

ReactionSystemPlaceboTAK-272 5 mgTAK-272 20 mgTAK-272 40 mgTAK-272 80 mgCandesartan Cilexetil 8 mg
NasopharyngitisInfections and infestations

Most-reported serious reactions: Diverticulum intestinal haemorrhagic, Adenocarcinoma gastric, Hepatocellular carcinoma, Prostate cancer, Cerebral infarction.

Data from ClinicalTrials.gov NCT02332824 adverse events section.

Sponsor's own description

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.

Publications & conference data

2 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Efficacy and Safety of Imarikiren in Patients with Type 2 Diabetes and Microalbuminuria: A Randomized, Controlled Trial.
    Ito S, Kagawa T, Saiki T, Shimizu K, et al · · 2019 · cited 6× · PMID 30755452 · DOI 10.2215/cjn.07720618
  2. Patient and Public Involvement (PPI) in outcome selection in breast cancer and nephrology trials.
    Buckley C, Treweek S, Laidlaw L, Shiely F. · · 2023 · cited 2× · PMID 36747232 · DOI 10.1186/s13063-022-06980-9

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