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Diabetes Mellitus, Type 2Phase 1NCT00949091

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

A Phase 1 study testing TAK-875 in people with Diabetes Mellitus, Type 2, run by Takeda.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 68 years
Conditions the study is for
Diabetes Mellitus, Type 2
What is being tested?
TAK-875
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
60 participants
Where
No sites listed yet
Study dates
Jan 2009to Jul 2009
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 68 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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.
  • Is willing to refrain from strenuous exercise from 72 hours before Check-in and throughout the study.
  • Is considered by the investigator to be in a good health (other than being diabetic) as determined during the medical history review, physical examination findings, electrocardiogram and vital sign results, and clinical laboratory evaluations.
  • Has creatinine clearance greater than 60 mL/min at Screening and Check-in.

Who cannot join

  • 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.
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  • 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.
  • Has a history of angioedema.
  • Had an acute, clinically significant illness within 30 days prior to Check-in, or any other condition or prior therapy that, in the opinion of the investigator, would make the subject unsuitable for the study.
  • Participant took or requires the use of any restricted medication or products within the timeframes listed.
  • Is participating in another investigational study or has taken any investigational drug within 30 days prior to Check-in.
  • Has poor venous access.
  • Has been randomized in a previous TAK-875 study within 6 months prior to the first dose of study drug.

About this study

Official title: 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

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.

Read the 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.

Being tested
TAK-875
Keywords
Diabetes Mellitus, Non Insulin Dependent, Diabetes Mellitus, Type II, Type 2 Diabetes Mellitus, Drug Therapy
Medical subject headings
Diabetes Mellitus, Type 2

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • TAK-875Drug

    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.

Study groups in NCT00949091
Study groupRoleWhat they receive
1ExperimentalNot described
Receives: Drug: TAK-875

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. TAK-875 maximum observed plasma concentration (Cmax)

    Measured: Day 14

  2. TAK-875 time at which Cmax occurred (Tmax)

    Measured: Day 14

  3. 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)

    Measured: Day 14

  4. TAK-875 renal clearance (CLr)

    Measured: Day 14

  5. TAK-875 metabolite (M-I) Cmax

    Measured: Day 14

  6. TAK-875 M-I Tmax

    Measured: Day 14

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

    Measured: Day 14

  8. TAK-875 M-I renal clearance CLr

    Measured: Day 14

Secondary outcomes (46)

  1. TAK-875 Cmax

    Measured: Day 1

  2. TAK-875 Tmax

    Measured: Day 1

  3. TAK-875 AUC(0-tau)

    Measured: Day 1

  4. TAK-875 renal clearance CLr

    Measured: Day 1

  5. M-I Tmax

    Measured: Day 1

  6. M-I Cmax

    Measured: Day 1

  7. M-I AUC(0-tau)

    Measured: Day 1

  8. M-I renal clearance CLr

    Measured: Day 1

  9. TAK-875 and M-I Cmax ratio

    Measured: Day 1

  10. TAK-875 and M-I Cmax ratio

    Measured: Day 14

  11. TAK-875 and M-I AUC(0-tau) ratio

    Measured: Day 1

  12. TAK-875 and M-I AUC(0-tau) ratio

    Measured: Day 14

  13. Percent changes from baseline to Day 14 in mean 4-hour concentration values for plasma glucose

    Measured: Day 14

  14. Percent changes from baseline to Day 14 in mean 4- hour concentration values for insulin

    Measured: Day 14

  15. Percent changes from baseline to Day 14 in mean 4- hour concentration values for proinsulin

    Measured: Day 14

  16. Percent changes from baseline to Day 14 in mean 4- hour concentration values for C-peptide

    Measured: Day 14

  17. Percent changes from baseline to Day 14 in mean 4- hour concentration values for glucagon

    Measured: Day 14

  18. Percent changes from baseline to Day 14 in mean 4- hour concentration values for total gastric inhibitory polypeptide (GIP)

    Measured: Day 14

  19. Percent changes from baseline to Day 14 in mean 4- hour concentration values for total glucagon-like peptide-1 (GLP-1)

    Measured: Day 14

  20. Percent changes from baseline to Day 14 in mean 24-hour concentration values for plasma glucose

    Measured: Day 14

  21. Percent changes from baseline to Day 14 in mean 24- hour concentration values for insulin

    Measured: Day 14

  22. Percent changes from baseline to Day 14 in mean 24- hour concentration values for proinsulin

    Measured: Day 14

  23. Percent changes from baseline to Day 14 in mean 24- hour concentration values for C-peptide

    Measured: Day 14

  24. Percent changes from baseline to Day 14 in mean 24- hour concentration values for glucagon

    Measured: Day 14

  25. Percent changes from baseline to Day 14 in mean 24- hour concentration values for total gastric inhibitory polypeptide (GIP)

    Measured: Day 14

  26. Percent changes from baseline to Day 14 in mean 24- hour concentration values for total glucagon-like peptide-1 (GLP-1)

    Measured: Day 14

  27. Absolute changes from baseline to Day 14 in mean 4-hour concentration values for plasma glucose

    Measured: Day 14

  28. Absolute changes from baseline to Day 14 in mean 4- hour concentration values for insulin

    Measured: Day 14

  29. Absolute changes from baseline to Day 14 in mean 4- hour concentration values for proinsulin

    Measured: Day 14

  30. Absolute changes from baseline to Day 14 in mean 4- hour concentration values for C-peptide

    Measured: Day 14

  31. Absolute changes from baseline to Day 14 in mean 4- hour concentration values for glucagon

    Measured: Day 14

  32. Absolute changes from baseline to Day 14 in mean 4- hour concentration values for total gastric inhibitory polypeptide (GIP)

    Measured: Day 14

  33. Absolute changes from baseline to Day 14 in mean 4- hour concentration values for total glucagon-like peptide-1 (GLP-1)

    Measured: Day 14

  34. Absolute changes from baseline to Day 14 in mean 24-hour concentration values for plasma glucose

    Measured: Day 14

  35. Absolute changes from baseline to Day 14 in mean 24- hour concentration values for insulin

    Measured: Day 14

  36. Absolute changes from baseline to Day 14 in mean 24- hour concentration values for proinsulin

    Measured: Day 14

  37. Absolute changes from baseline to Day 14 in mean 24- hour concentration values for C-peptide

    Measured: Day 14

  38. Absolute changes from baseline to Day 14 in mean 24- hour concentration values for glucagon

    Measured: Day 14

  39. Absolute changes from baseline to Day 14 in mean 24- hour concentration values for total gastric inhibitory polypeptide (GIP)

    Measured: Day 14

  40. Absolute changes from baseline to Day 14 in mean 24- hour concentration values for total glucagon-like peptide-1 (GLP-1)

    Measured: Day 14

  41. Percent change from baseline to 24-hours post Day 13 dose in homeostasis model assessment of ß-cell function

    Measured: Day 13

  42. Percent change from baseline to 24-hours post Day 14 dose in homeostasis model assessment of ß-cell function

    Measured: Day 14

  43. Absolute change from baseline to 24-hours post Day 13 dose in homeostasis model assessment of ß-cell function

    Measured: Day 13

  44. Absolute change from baseline to 24-hours post Day 14 dose in homeostasis model assessment of ß-cell function

    Measured: Day 14

  45. Percent change from baseline to Day 14 in insulinogenic index

    Measured: Day 14

  46. Absolute change from baseline to Day 14 in insulinogenic index

    Measured: Day 14

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted30 Jul 2009 (estimated)
  2. Study startJan 2009
  3. Primary completionJul 2009
  4. Study completionJul 2009

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Basic science
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
60 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00949091
Sponsor's protocol ID
TAK-875_102
Other IDs
U1111-1114-2888
Status last verified
Jun 2010
First submitted
28 Jul 2009
Last updated
11 Jun 2010
Results posted
No
Data monitoring committee
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing TAK-875 in people with Diabetes Mellitus, Type 2, run by Takeda.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 18 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 11 Jun 2010. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

TAK-875 maximum observed plasma concentration (Cmax) (time frame: Day 14). The study lists 8 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00949091.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Jun 2010.

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