Recent Updates
Recently added Catalysts

TAK-272

Phase 2

Type 2 Diabetes Mellitus and Microalbuminuria | Small molecule | Metabolic |Takeda Pharmaceutical Company Limited|Last Updated: Aug 13, 2018

Success Probability

Subscribe to view

Market & Valuation

Subscribe to view

Trial Design

RandomizedDouble-BlindPLACEBO_CONTROLLED
Total Trials1
Total Enrollment415

FDA Designations

No designations recorded

Clinical trial landscape

TAK-272 · 3 trials · 4 indications

Phase 2 1Phase 1 2
NCT02332824A Phase 2 Dose-finding Study of TAK-272 in Participants With Type 2 Diabetes Mellitus and MicroalbuminuriaType 2 Diabetes Mellitus and Microalbuminuria
COMPLETED415 Analytics
PHASE2COMPLETED
A Phase 2 Dose-finding Study of TAK-272 in Participants With Type 2 Diabetes Mellitus and Microalbuminuria
Type 2 Diabetes Mellitus and MicroalbuminuriaUnlock trial analytics

Study Endpoints

Primary Endpoints

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)
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.

AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for Free Form of TAK-272 (TAK-272F) and Its Metabolite M-I
Day 1: Pre-dose and at multiple time points (0.5, 1, 1.5, 2, 3, 4, 5, 8, 10, 12, 14, 24, 36, 48, 72, 96, 120 hours post dose; up to 120 hours) post-dose
Cmax: Maximum Observed Plasma Concentration for TAK-272F and Its Metabolite M-I
Day 1: Pre-dose and at multiple time points (0.5, 1, 1.5, 2, 3, 4, 5, 8, 10, 12, 14, 24, 36, 48, 72, 96, 120 hours post dose; up to 120 hours) post-dose
AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-272F and Its Metabolite M-I
Day 1: Pre-dose and at multiple time points (0.5, 1, 1.5, 2, 3, 4, 5, 8, 10, 12, 14, 24, 36, 48, 72, 96, 120 hours post dose; up to 120 hours) post-dose
AUClast,u: Area Under the Unbound Plasma Concentration-time Curve From Time 0 to Time of Last Quantifiable Concentration for TAK-272F
Day 1: Pre-dose and at multiple time points (0.5, 1, 1.5, 2, 3, 4, 5, 8, 10, 12, 14, 24, 36, 48, 72, 96, 120 hours post dose; up to 120 hours) post-dose

AUClast,u is the area under the concentration-time curve of the unbound drug in plasma over the time interval from 0 to time of last quantifiable post-dose of TAK-272.

Cmax,u: Maximum Unbound Plasma Concentration for TAK-272F
Day 1: Pre-dose and at multiple time points (0.5, 1, 1.5, 2, 3, 4, 5, 8, 10, 12, 14, 24, 36, 48, 72, 96, 120 hours post dose; up to 120 hours) post-dose

Cmax,u is the peak unbound plasma concentration of a drug after administration, obtained directly from the unbound plasma concentration-time curve.

AUC∞,u: Area Under the Unbound Plasma Concentration-time Curve From Time 0 to Infinity for TAK-272F
Day 1: Pre-dose and at multiple time points (0.5, 1, 1.5, 2, 3, 4, 5, 8, 10, 12, 14, 24, 36, 48, 72, 96, 120 hours post dose; up to 120 hours) post-dose

AUC∞,u is the area under the concentration-time curve of the unbound drug in plasma over the time interval from 0 to infinity of TAK-272.

Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-272F and Its Metabolite M-I
Day 1: Pre-dose and at multiple time points (0.5, 1, 1.5, 2, 3, 4, 5, 8, 10, 12, 14, 24, 36, 48, 72, 96, 120 hours post dose; up to 120 hours) post-dose
Apparent Clearance (CL/F) for TAK-272F
Day 1: Pre-dose and at multiple time points (0.5, 1, 1.5, 2, 3, 4, 5, 8, 10, 12, 14, 24, 36, 48, 72, 96, 120 hours post dose; up to 120 hours) post-dose
CLu/F: Apparent Clearance for Unbound Drug After Extravascular Administration for TAK-272F
Day 1: Pre-dose and at multiple time points (0.5, 1, 1.5, 2, 3, 4, 5, 8, 10, 12, 14, 24, 36, 48, 72, 96, 120 hours post dose; up to 120 hours) post-dose

CLu/F is the apparent clearance for unbound drug after extravascular administration of TAK-272.

Cumulative Urinary Excretion Ratio of TAK-272F and Its Metabolite M-I From 0 to 72 Hours Post-dose in Cohorts 1R, 2R, 3R, 4R, 1H, 2H and 3H
Day 1: Pre-dose and at multiple time points (4, 8, 12, 24, 36, 48, 72 hours post dose; up to 72 hours) post-dose

Urinary excretion ratio (percentage \[%\] of dose) of TAK-272 and its metabolite M-I in urine was calculated for each participant.

Plasma Protein Binding Rate of TAK-272F in Cohorts 1R, 2R, 3R, 4R, 5R, 1H, 2H and 3H
Baseline

Plasma protein binding rate was the percentage of unbound fraction of TAK-272F in plasma protein.

Excretion Ratio of TAK-272F in Dialysate in Cohort 5R
Day 1: Pre-dose, up to 6 hours post-dose

Excretion ratio (% of dose) of TAK-272F in dialysis fluid was calculated for each participant.

Cmax: Maximum Observed Plasma Concentration for TAK 272F and TAK 272-Metabolite (M-I) in Cohort 1
Day 1 and Day 10: pre-dose and at multiple time-points (upto 72 hours) postdose; Day 1 for Cohort 1: TAK-272 and Day 10 for Cohort 1: TAK-272 + Itraconazole
AUC(0-inf): Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK 272F and TAK 272-M-I in Cohort 1
Day 1 and Day 10: pre-dose and at multiple time-points (upto 72 hours) postdose; Day 1 for Cohort 1: TAK-272 and Day 10 for Cohort 1: TAK-272 + Itraconazole
AUC(0-tlqc): Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK 272F and TAK 272-M-I in Cohort 1
Day 1 and Day 10: pre-dose and at multiple time-points (upto 72 hours) postdose; Day 1 for Cohort 1: TAK-272 and Day 10 for Cohort 1: TAK-272 + Itraconazole
Cumulative Urinary Excretion Ratio of TAK 272F and TAK 272-M-I From 0 to 72 Hours Postdose in Cohort 1
Day 1 and Day 10: pre-dose and at multiple time-points (upto 72 hours) postdose; Day 1 for Cohort 1: TAK-272 and Day 10 for Cohort 1: TAK-272 + Itraconazole
Cmax: Maximum Observed Plasma Concentration for Digoxin in Cohort 2
Day 1 and Day 7: pre-dose and at multiple time-points (upto 48 hours) postdose; Day 1 for Cohort 2: Digoxin and Day 7 for Cohort 2: Digoxin + TAK-272
AUC(0-inf): Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for Digoxin in Cohort 2
Day 1 and Day 7: pre-dose and at multiple time-points (upto 48 hours) postdose; Day 1 for Cohort 2: Digoxin and Day 7 for Cohort 2: Digoxin + TAK-272
AUC(0-tlqc): Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for Digoxin in Cohort 2
Day 1 and Day 7: pre-dose and at multiple time-points (upto 48 hours) postdose; Day 1 for Cohort 2: Digoxin and Day 7 for Cohort 2: Digoxin + TAK-272
Urinary Excretion Ratio of Digoxin From 0 to 48 Hours Postdose in Cohort 2
Day 1 and Day 7: pre-dose and at multiple time-points (upto 48 hours) postdose; Day 1 for Cohort 2: Digoxin and Day 7 for Cohort 2: Digoxin + TAK-272
Cmax: Maximum Observed Plasma Concentration for Midazolam and 1'Hydroxymidazolam in Cohort 2
Day 1 and Day 7: pre-dose and at multiple time-points (upto 24 hours) postdose; Day 1 for Cohort 2: Midazolam and Day 7 for Cohort 2: Midazolam + TAK-272
AUC(0-inf): Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for Midazolam and 1'Hydroxymidazolam in Cohort 2
Day 1 and Day 7: pre-dose and at multiple time-points (upto 24 hours) postdose; Day 1 for Cohort 2: Midazolam and Day 7 for Cohort 2: Midazolam + TAK-272
AUC(0-tlqc): Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for Midazolam and 1'Hydroxymidazolam in Cohort 2
Day 1 and Day 7: pre-dose and at multiple time-points (upto 24 hours) postdose; Day 1 for Cohort 2: Midazolam and Day 7 for Cohort 2: Midazolam + TAK-272
Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs)
Cohort 1: Baseline up to Day 19; Cohort 2: Baseline up to Day 15
Number of Participants With TEAEs Related to Vital Signs
Cohort 1: Baseline up to Day 19; Cohort 2: Baseline up to Day 15
Number of Participants With TEAEs Related to Body Weight
Cohort 1: Baseline up to Day 19; Cohort 2: Baseline up to Day 15
Number of Participants Who Had Clinically Significant Changes From Baseline in 12-lead Electrocardiograms
Cohort 1: Baseline up to Day 19; Cohort 2: Baseline up to Day 15

Number of participants who had ECG findings changed from "within normal limit" or "abnormal, clinically significant" to "abnormal and clinically significant" after study drug administration.

Number of Participants With TEAEs Categorized Into Investigations System Organ Class (SOC) Related to Chemistry, Hematology or Urinalysis
Cohort 1: Baseline up to Day 19; Cohort 2: Baseline up to Day 15
Number of Participants With Clinically Significant Change From Baseline in Continuous Pulse Oximetry (SpO2) in Cohort 2
Cohort 2: Baseline up to Day 15

Secondary Endpoints

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
Unlock Study Endpoints

Study Design & Arms

AllocationRANDOMIZED
MaskingQUADRUPLE
ModelPARALLEL
PurposeTREATMENT

Treatment Arms

ArmTypeDescription
PlaceboPLACEBO_COMPARATORTAK-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 mgEXPERIMENTALTAK-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 mgEXPERIMENTALTAK-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 mgEXPERIMENTALTAK-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 mgEXPERIMENTALTAK-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 mgACTIVE_COMPARATORTAK-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).
Participants with normal renal function: TAK-272 40 mgACTIVE_COMPARATORFasted single oral administration of TAK-272 40 milligram (mg)
Participants with mild renal impairment: TAK-272 40 mgEXPERIMENTALFasted single oral administration of TAK-272 40 mg
Participants with moderate renal impairment: TAK-272 40 mgEXPERIMENTALFasted single oral administration of TAK-272 40 mg
Participants with severe renal impairment: TAK-272 40 mgEXPERIMENTALFasted single oral administration of TAK-272 40 mg
Hemodialysis participants: TAK-272 40 mgEXPERIMENTALFasted single oral administration of TAK-272 40 mg
Participants with normal hepatic function: TAK-272 40 mgACTIVE_COMPARATORFasted single oral administration of TAK-272 40 mg
Participants with mild hepatic impairment: TAK-272 40 mgEXPERIMENTALFasted single oral administration of TAK-272 40 mg
Participants with moderate hepatic impairment: TAK-272 40 mgEXPERIMENTALFasted single oral administration of TAK-272 40 mg
Cohort 1: TAK-272 + ItraconazoleEXPERIMENTALTAK-272 40 mg, tablet, orally, once on Day 1 and 10, followed by Itraconazole 200 mg, solution, orally, twice on Day 4, further followed by Itraconazole 200 mg, solution, orally, once from Day 5 to 12.
Cohort 2: Midazolam + Digoxin + TAK-272EXPERIMENTALMidazolam 2 mg, syrup, and Digoxin 0.25 mg, tablet, orally, once on Day 1 and 7, followed by TAK-272 80 mg, tablet, orally, once from Day 3 to 8.

Interventions

NameTypeDescription
TAK-272DRUGTAK-272 tablets
TAK-272 PlaceboDRUGTAK-272 placebo-matching tablets
Candesartan cilexetilDRUGCandesartan cilexetil tablets
Candesartan cilexetil PlaceboDRUGCandesartan cilexetil placebo-matching tablets
DigoxinDRUGDigoxin tablet.
ItraconazoleDRUGItraconazole oral solution
MidazolamDRUGMidazolam syrup.
Unlock Study Design Details

Eligibility Criteria

Age Range20 Years to 74 Years
SexALL
Healthy VolunteersNo
Study Sites68

Inclusion Criteria: * 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 participa...

Countries:Japan
Unlock Eligibility Criteria

Frequently asked questions about TAK-272

What is TAK-272 used for?

TAK-272 is an investigational small molecule being studied for use in Type 2 Diabetes Mellitus with microalbuminuria, as well as in renal impairment, hepatic impairment, and in Japanese healthy adult males for pharmacokinetic and drug interaction studies. It is developed by Takeda Pharmaceutical Company Limited.

Who is developing TAK-272?

TAK-272 is being developed by Takeda Pharmaceutical Company Limited, whose stock trades under the ticker TAK. The company has conducted clinical trials of TAK-272 in Japan across multiple indications.

What phase is TAK-272 in?

TAK-272 has completed Phase 1 and Phase 2 clinical trials. The Phase 2 trial was a dose-finding study in participants with Type 2 Diabetes Mellitus and microalbuminuria, while Phase 1 trials evaluated pharmacokinetics and drug interactions. TAK-272 remains investigational and is not approved.

What clinical trials has TAK-272 been in?

TAK-272 has been studied in three completed trials in Japan. NCT02332824 was a Phase 2 dose-finding study in Type 2 Diabetes Mellitus with microalbuminuria. NCT02367872 was a Phase 1 pharmacokinetic study in renal or hepatic impairment. NCT02370615 was a Phase 1 drug-drug interaction study in healthy Japanese males.

Is TAK-272 the same as any other drug?

TAK-272 is the code name used by Takeda for this investigational compound. No alternative names are available in the clinical trial records, so it is referred to solely as TAK-272 in the studies conducted.