Clinical Trials/NCT00949091

NCT00949091

Completed

Phase 1

A Phase 1, Double-Blind, Randomized, Placebo-Controlled, Sequential, Multiple Ascending-Dose Study to Evaluate the Pharmacokinetics and Pharmacodynamics of TAK-875 in Subjects With Type 2 Diabetes

Takeda0 sites60 target enrollmentJanuary 2009

ConditionsDiabetes Mellitus, Type 2

InterventionsTAK-875

DrugsTAK-875

Overview

Phase: Phase 1
Intervention: TAK-875
Conditions: Diabetes Mellitus, Type 2
Sponsor: Takeda
Enrollment: 60
Primary Endpoint: TAK-875 maximum observed plasma concentration (Cmax)
Status: Completed
Last Updated: 15 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Similar Trials

Overview

Brief Summary

The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of multiple ascending-doses of TAK-875 in subjects with type 2 diabetes mellitus.

Detailed Description

TAK-875 is being developed as an adjunct to diet and exercise to improve glycemic control in patients with type 2 diabetes mellitus. Nonclinical data suggest that TAK-875 stimulates insulin secretion only at elevated blood glucose levels, with the potential for low hypoglycemic side effects. The purpose of this phase 1, multiple ascending-dose study is to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of once daily oral doses of TAK-875 for 14 days in subjects with type 2 diabetes mellitus. Participants will be housed for a total of 8 consecutive overnight stays in the clinic, and will undergo oral glucose tolerance tests and standardized meal tests with multiple blood sampling throughout their clinic stay.

Registry

clinicaltrials.gov

Start Date

January 2009

End Date

July 2009

Last Updated

15 years ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

Takeda

Eligibility Criteria

Inclusion Criteria

•Participants with type 2 diabetes who are newly diagnosed, managed with diet and exercise alone, or taking up to 2 oral antidiabetic agents (except thiazolidinediones) and willing to discontinue the antidiabetic medication(s) 2 weeks prior to randomization.
•Meets one of the following glycosylated hemoglobin criteria (diagnosis must be based on current American Diabetes Association criteria) at Screening:
•If treatment naïve, should have a glycosylated hemoglobin concentration greater than or equal to 6.5% and less than or equal to 10.0%.
•If on a single antidiabetic agent (stable dose for at least 28 days), should have a glycosylated hemoglobin greater than or equal to 6% and less than or equal to 9.5%.
•If on a combination of up to 2 antidiabetic agents (stable doses for at least 28 days), should have a glycosylated hemoglobin greater than or equal to 6% and less than or equal to 9.0%.
•Has fasting plasma glucose greater than 126 mg/dL and less than 260 mg/dL if not on any antidiabetic medication, or less than 220 mg/dL if on any single antidiabetic agent, and less than 200 mg/dL if on any combination of 2 oral antidiabetic agents at Screening.
•Has fasting C-peptide concentration greater than or equal to 0.8 ng/mL at Screening.
•Weighs at least 50 kg (110 lb) and has a body mass index between 18 and 40 kg/m2, inclusive at Screening.
•Has not received treatment with weight-loss drugs within the 3 months prior to Screening.
•Has a systolic blood pressure less than or equal to 160 mm Hg and a diastolic blood pressure of less than or equal to 100 mm Hg at Screening and at Check-in (Day -2).

Exclusion Criteria

•Has a history of abdominal surgery (except laparoscopic cholecystectomy or uncomplicated appendectomy), thoracic, or nonperipheral vascular surgery within 6 months prior to Check-in.
•Has a known hypersensitivity to TAK-875, or other related compounds.
•Has a history of cardiac arrhythmia, systolic dysfunction congestive heart failure, angina, myocardial ischemia or infarction, or stroke within 1 year prior to Screening, or the presence of an abnormal electrocardiogram that, in the investigator's opinion, is clinically significant.
•Has a history of drug abuse or a history of alcohol abuse within 2 years prior to Screening.
•Has used any tobacco (ie, nicotine) products within 90 days prior to Check-in, and is unwilling to abstain from these products for the duration of the study.
•Has a history of cancer that has not been in remission for at least 5 years prior to the first dose of study drug. This criterion does not apply to basal cell or stage I squamous cell carcinoma of the skin.
•Has an alanine aminotransferase, alkaline phosphatase or aspartate aminotransferase level greater than or equal to 2 times the upper limit normal for the testing laboratory, active liver disease, or jaundice at Screening or Check-in.
•Has a total bilirubin greater than 2 mg/dL at Screening or Check-in.
•Has donated blood or experienced acute blood loss (including plasmapheresis) of greater than 500 mL within 90 days prior to the first dose of study drug.
•Participant is on any insulin treatment.

Arms & Interventions

1

Intervention: TAK-875

Outcomes

Primary Outcomes

TAK-875 maximum observed plasma concentration (Cmax)

Time Frame: Day 14

TAK-875 time at which Cmax occurred (Tmax)

Time Frame: Day 14

TAK-875 area under the plasma concentration-time curve from time 0 to time tau, where tau is the length of a dosing interval AUC(0-tau)

Time Frame: Day 14

TAK-875 renal clearance (CLr)

Time Frame: Day 14

TAK-875 metabolite (M-I) Cmax

Time Frame: Day 14

TAK-875 M-I Tmax

Time Frame: Day 14

TAK-875 M-I AUC(0-tau)

Time Frame: Day 14

TAK-875 M-I renal clearance CLr

Time Frame: Day 14

Secondary Outcomes

TAK-875 Cmax(Day 1)
TAK-875 Tmax(Day 1)
TAK-875 AUC(0-tau)(Day 1)
TAK-875 renal clearance CLr(Day 1)
M-I Tmax(Day 1)
M-I Cmax(Day 1)
M-I AUC(0-tau)(Day 1)
M-I renal clearance CLr(Day 1)
TAK-875 and M-I Cmax ratio(Day 14)
TAK-875 and M-I AUC(0-tau) ratio(Day 14)
Percent changes from baseline to Day 14 in mean 4-hour concentration values for plasma glucose(Day 14)
Percent changes from baseline to Day 14 in mean 4- hour concentration values for insulin(Day 14)
Percent changes from baseline to Day 14 in mean 4- hour concentration values for proinsulin(Day 14)
Percent changes from baseline to Day 14 in mean 4- hour concentration values for C-peptide(Day 14)
Percent changes from baseline to Day 14 in mean 4- hour concentration values for glucagon(Day 14)
Percent changes from baseline to Day 14 in mean 4- hour concentration values for total gastric inhibitory polypeptide (GIP)(Day 14)
Percent changes from baseline to Day 14 in mean 4- hour concentration values for total glucagon-like peptide-1 (GLP-1)(Day 14)
Percent changes from baseline to Day 14 in mean 24-hour concentration values for plasma glucose(Day 14)
Percent changes from baseline to Day 14 in mean 24- hour concentration values for insulin(Day 14)
Percent changes from baseline to Day 14 in mean 24- hour concentration values for proinsulin(Day 14)
Percent changes from baseline to Day 14 in mean 24- hour concentration values for C-peptide(Day 14)
Percent changes from baseline to Day 14 in mean 24- hour concentration values for glucagon(Day 14)
Percent changes from baseline to Day 14 in mean 24- hour concentration values for total gastric inhibitory polypeptide (GIP)(Day 14)
Percent changes from baseline to Day 14 in mean 24- hour concentration values for total glucagon-like peptide-1 (GLP-1)(Day 14)
Absolute changes from baseline to Day 14 in mean 4-hour concentration values for plasma glucose(Day 14)
Absolute changes from baseline to Day 14 in mean 4- hour concentration values for insulin(Day 14)
Absolute changes from baseline to Day 14 in mean 4- hour concentration values for proinsulin(Day 14)
Absolute changes from baseline to Day 14 in mean 4- hour concentration values for C-peptide(Day 14)
Absolute changes from baseline to Day 14 in mean 4- hour concentration values for glucagon(Day 14)
Absolute changes from baseline to Day 14 in mean 4- hour concentration values for total gastric inhibitory polypeptide (GIP)(Day 14)
Absolute changes from baseline to Day 14 in mean 4- hour concentration values for total glucagon-like peptide-1 (GLP-1)(Day 14)
Absolute changes from baseline to Day 14 in mean 24-hour concentration values for plasma glucose(Day 14)
Absolute changes from baseline to Day 14 in mean 24- hour concentration values for insulin(Day 14)
Absolute changes from baseline to Day 14 in mean 24- hour concentration values for proinsulin(Day 14)
Absolute changes from baseline to Day 14 in mean 24- hour concentration values for C-peptide(Day 14)
Absolute changes from baseline to Day 14 in mean 24- hour concentration values for glucagon(Day 14)
Absolute changes from baseline to Day 14 in mean 24- hour concentration values for total gastric inhibitory polypeptide (GIP)(Day 14)
Absolute changes from baseline to Day 14 in mean 24- hour concentration values for total glucagon-like peptide-1 (GLP-1)(Day 14)
Percent change from baseline to 24-hours post Day 13 dose in homeostasis model assessment of ß-cell function(Day 13)
Percent change from baseline to 24-hours post Day 14 dose in homeostasis model assessment of ß-cell function(Day 14)
Absolute change from baseline to 24-hours post Day 13 dose in homeostasis model assessment of ß-cell function(Day 13)
Absolute change from baseline to 24-hours post Day 14 dose in homeostasis model assessment of ß-cell function(Day 14)
Percent change from baseline to Day 14 in insulinogenic index(Day 14)
Absolute change from baseline to Day 14 in insulinogenic index(Day 14)