Pharmacokinetics and Pharmacodynamics of TAK-875 in Subjects With Type 2 Diabetes

NCT00949091 | Completed Phase 1

• 2 other identifiers: TAK-875_102U1111-1114-2888
• Study Type: interventional
• Target: 60
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Diabetes Mellitus, Type 2

Keywords

Diabetes Mellitus, Non Insulin Dependent; Diabetes Mellitus, Type II; Type 2 Diabetes Mellitus; Drug Therapy

Outcome Measures

Primary Outcomes (8)

• TAK-875 maximum observed plasma concentration (Cmax)

  Day 14

• TAK-875 time at which Cmax occurred (Tmax)

  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)

  Day 14

• TAK-875 renal clearance (CLr)

  Day 14

• TAK-875 metabolite (M-I) Cmax

  Day 14

• TAK-875 M-I Tmax

  Day 14

• TAK-875 M-I AUC(0-tau)

  Day 14

• TAK-875 M-I renal clearance CLr

  Day 14

Secondary Outcomes (46)

• 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

Study Arms (1)

1

EXPERIMENTAL

Drug: TAK-875

Interventions

TAK-875 DRUG

Randomized, multiple ascending-dose sequence over 14 consecutive days to include the following: TAK-875 25 mg tablets, orally TAK-875 50 mg tablets, orally TAK-875 100 mg tablets, orally TAK-875 200 mg tablets, orally TAK-875 400 mg tablets, orally TAK-875 placebo-matching tablets, orally.

1

Eligibility Criteria

• Age: 18 Years - 68 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).
• Female participant is not of child-bearing potential (ie, surgically sterile \[hysterectomy, bilateral oophorectomy, or 2 years post-tubal ligation\] or postmenopausal \[2 years since last menses\]).
• Is able and willing to monitor blood glucose concentrations with a home glucose monitor during the Washout Interval and record results in the daily diary.
• Has negative test results at Screening and Check-in for selected substances of abuse, including alcohol and cotinine.
• Has Screening and Check-in clinical laboratory evaluations \[including fasting clinical chemistry, hematology, and complete urinalysis (excluding glucose results)\] within the reference range for the testing laboratory, unless the investigator deems the out-of-range results to be not clinically significant.
• Has negative test results for hepatitis B surface antigen and antibody to hepatitis C virus, and no known history of human immunodeficiency virus.

You may not qualify if:

• 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.
• The subject has a history of proteinuria greater than 300 mg/day on a 12- or 24-hour urine collection or an albumin/creatinine ratio greater than 300 μg/mg at Screening. If elevated, the subject may be rescreened within 1 week, and may be included in study with agreement between Principal Investigator and the Takeda Global Research and Development Medical Monitor.
• Has a history of any clinically significant retinopathy, which is defined as more than moderate nonproliferative diabetic retinopathy or any stage of proliferative diabetic retinopathy or any history of laser-treated retinopathy.
• Has history of treated or clinically significant peripheral or autonomic neuropathy.
• The subject has a history of ulcerative colitis or Crohn's disease, or has undergone gastric resection.
• The subject has a history of a psychiatric disorder that will affect the subject's ability to participate in the study.

Sponsors & Collaborators

• Takeda: lead

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

TAK-875

Condition Hierarchy (Ancestors)

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

Study Officials

• Medical Director Clinical Science

  Takeda

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: July 28, 2009
• First Posted: July 30, 2009
• Study Start: January 1, 2009
• Primary Completion: July 1, 2009
• Study Completion: July 1, 2009
• Last Updated: June 11, 2010

Record last verified: 2010-06