Type II diabetes mellitus.
Conditions
Sponsors
Takeda Global Research & Development Center, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: In order to be eligible for this study, each of the following criteria must be satisfied with a “YES” answer (unless not applicable): • Males or females, 18 to 80 years of age, inclusive, with a historical diagnosis of type 2 diabetes mellitus who are currently treated with metformin alone but who are experiencing inadequate glycemic control. The subject should have received the metformin monotherapy for at least the 3 months prior to Screening; and the subject must have a stable dose =1500 mg metformin for at least 8 weeks prior to randomization. Subjects with a maximum tolerated dose that is documented to be less than 1500 mg of metformin may also be enrolled if this dose has been stable for 8 weeks prior to randomization. • No treatment with antidiabetic agents other than metformin within the 3 months prior to Screening. (Exception: if a subject has received other antidiabetic therapy for less than 7 days within the 3 months prior to Screening.) • Body mass index =23 kg/m2 and =45 kg/m2 • Fasting C-peptide concentration =0.8 ng/mL (=0.26 nmol/L). (If this screening criterion is not met, the subject still qualifies if C-peptide =1.5 ng/mL (=0.50 nmol/L) after a challenge test. See Appendix E.) • HbA1c concentration between 7.0% and 10.0%, inclusive • If regular use of other, nonexcluded medications, must be on a stable dose for at least the 4 weeks prior to Screening. However, PRN (as needed) use of prescription or over-the-counter medications is allowed at the discretion of the investigator. • Systolic blood pressure =180 mm Hg and diastolic pressure =110 mm Hg • Hemoglobin =12 g/dL (=120 gm/L) for males and =10 g/dL (=100 gm/L) for females • Alanine aminotransferase =3 x upper limit of normal • Serum creatinine <1.5 mg/dL (<133 micromol/L) for males and <1.4 mg/dL (<124 micromol/L) for females. • Thyroid-stimulating hormone level = the upper limit of the normal range and the subject is clinically euthyroid • Neither pregnant (confirmed by laboratory testing in females of childbearing potential) nor lactating • Female subjects of childbearing potential (ie, not surgically sterile and/or not postmenopausal) must be practicing adequate contraception. Methods of adequate contraception include the following: intrauterine device; doublebarrier device such as a diaphragm or condom plus spermicide; or a hormonal contraceptive (including injectable, implantable, or oral). Adequate contraception must be practiced for the duration of participation in the study. • Able and willing to monitor their own blood glucose concentrations with a home glucose monitor • No major illness or debility that in the investigator’s opinion prohibits the subject from completing the study • Able and willing to provide written informed consent Additional Inclusion Criteria for Randomization: In order to be eligible for randomization, each of the following additional criteria must be satisfied with a “YES” answer: • HbA1c concentration between 7.0% and 10.0%, inclusive at the Week -1 visit. (Of note, if the subject does not qualify for randomization based on this criterion, the assessment may be repeated on a weekly basis, for a maxi
Exclusion criteria
Exclusion criteria: In order to be eligible for this study, each of the following criteria must be satisfied with a “NO” answer: • Urine albumin/creatinine ratio of >1000 µg/mg (> 113 mg/mol) at Screening. If elevated, the subject may be rescreened within 1 week. • History of cancer, other than squamous cell or basal cell carcinoma of the skin, that has not been in full remission for at least 5 years prior to Screening. (A history of treated CIN I or CIN II [cervical intraepithelial neoplasia] is allowed.) • History of laser treatment for proliferative diabetic retinopathy within the 6 months prior to Screening • History of treated diabetic gastric paresis • New York Heart Association Class III or IV heart failure regardless of therapy. Currently treated subjects who are stable at Class I or II are candidates for the study (see Appendix F). • History of coronary angioplasty, coronary stent placement, coronary bypass surgery, or myocardial infarction within the 6 months prior to Screening • History of any hemoglobinopathy that may affect determination of HbA1c • History of infection with hepatitis B, hepatitis C, or human immunodeficiency virus • History of a psychiatric disorder that will affect the subject’s ability to participate in the study • History of angioedema in association with use of angiotensin-converting enzyme inhibitors or angiotensin-II receptor inhibitors • History of alcohol or substance abuse within the 2 years prior to Screening • Receipt of any investigational drug within the 30 days prior to Screening or a history of receipt of an investigational antidiabetic drug within the 3 months prior to Screening • Prior treatment in an investigational study of SYR-322
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Secondary Objective: • To evaluate other measures of glycemic control after treatment with SYR-322 in combination with metformin as compared with metformin alone • To evaluate changes in pancreatic function after treatment with SYR-322 in combination with metformin as compared with metformin alone • To evaluate changes in body weight following treatment with SYR-322 in combination with metformin as compared with metformin alone • To evaluate the safety of SYR-322 in combination with metformin as compared with metformin alone • To evaluate plasma concentrations of SYR-322 using a sparse sampling approach • To evaluate clinically meaningful levels of response in HbA1c after treatment with SYR-322 in combination with metformin as compared with metformin alone ;Main Objective: • To evaluate the efficacy of SYR-322 administered in combination with metformin as compared with metformin alone on glycosylated hemoglobin (HbA1c) change from baseline;Primary end point(s): The primary endpoint will be change from baseline in HbA1c at Week 26. | — |
Countries
Czech Republic, Germany, Hungary, Spain, United Kingdom
Outcome results
None listed