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 insulin alone (with or without metformin). Metformin dose should have been stable for at least 8 weeks prior to randomization. • No treatment with antidiabetic agents other than insulin and metformin within the 8 weeks prior to Randomization. • Body mass index =23 kg/m2 and =45 kg/m2 • Fasting C-peptide concentration =0.8 ng/mL. (If this screening criterion is not met, the subject still qualifies if C-peptide =1.5 ng/mL after a challenge test. See Appendix E.) • HbA1c concentration =8.0% at Screening • Using a stable dose of insulin of at least 15 units but not more than 100 units per day for at least the last 8 weeks prior to Randomization. A dose of insulin that varies by up to 15% of the mean will be considered as stable. • 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 for males and =10 g/dL for females • Alanine aminotransferase =3 x upper limit of normal • Serum creatinine =2.0 mg/dL • 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 =8.0% 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 maximum of 4 additional weeks.) • Have been at least 75% compliant with the single-blind placebo regimen during the run-in/stabilization period, as assessed by tablet count • No use of oral or systemically injected glucocorticoids or use of weight-loss drugs is allowed within the 3 months prior to randomization. (Inhaled corticosteroids are allowed.) Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
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 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 |
|---|---|
| Main Objective: • To evaluate the efficacy of SYR-322 administered in combination with insulin as compared with insulin alone on glycosylated hemoglobin (HbA1c) change from baseline;Secondary Objective: • To evaluate other measures of glycemic control after treatment with SYR-322 in combination with insulin as compared with insulin alone • To evaluate changes in pancreatic function after treatment with SYR-322 in combination with insulin as compared with insulin alone • To evaluate changes in body weight following treatment with SYR-322 in combination with insulin as compared with insulin alone • To evaluate the safety of SYR-322 in combination with insulin as compared with insulin 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 insulin as compared with insulin alone;Primary end point(s): The primary endpoint will be change from baseline in HbA1c at Week 26. | — |
Countries
Czech Republic, Germany, Hungary, Spain
Outcome results
None listed