Efficacy and Safety Study of SYR-619 in Treating Subjects With Type 2 Diabetes Mellitus
Primary Purpose
Diabetes Mellitus
Status
Terminated
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
SYR-619
SYR-619
SYR-619
SYR-619
Placebo
Alogliptin
Sponsored by
About this trial
This is an interventional treatment trial for Diabetes Mellitus focused on measuring Glucose Metabolism Disorder, Dysmetabolic Syndrome, Type II Diabetes, Diabetes Mellitus, Lipoatrophic, Dyslipidemia, Drug Therapy
Eligibility Criteria
Inclusion Criteria:
- Male or female, with a historical diagnosis of type 2 diabetes mellitus.
- Treatment for diabetes with either lifestyle modification or metformin or sulfonylurea alone for at least the 2 months prior to Screening; and a stable dose of either metformin or sulfonylurea for at least 12 weeks prior to randomization for subjects receiving metformin or sulfonylurea at Screening.
- Those subjects receiving metformin or sulfonylurea monotherapy at randomization must have been at least 75% compliant with their metformin or sulfonylurea regimen during the run in/stabilization period, as assessed by subject diary and investigator assessment.
- No treatment with antidiabetic agents other than metformin alone or sulfonylurea alone within the 3 months prior to Screening.
- Glycosylated hemoglobin concentration between 7.0% and 10.0%, inclusive, and a fasting plasma glucose <275 mg/dL (<15.27 mmol/L) at the Week -1 visit.
- Body mass index ≥23 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).
- If regular use of other non-excluded medications, must be on a stable dose for at least the 4 weeks prior to Screening. However, as needed use of prescription or over-the-counter medications is allowed at the discretion of the investigator.
- Systolic blood pressure <160 mm Hg and diastolic pressure <100 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.
- Urine albumin/creatinine ratio of <1000 μg/mg (113 mg/mol) at Screening. If elevated, the subject may be rescreened within 1 week.
- Thyroid-stimulating hormone level ≤ the upper limit of the normal range and the subject has normal thyroid function (clinically euthyroid)
- A female subject of childbearing potential who is sexually active must agree to use adequate contraception, and must be neither pregnant nor lactating from Screening and throughout the duration of 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.
Exclusion Criteria:
- Concurrently treated with combined metformin and sulfonylurea antidiabetic therapy.
- 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.
- 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.
- 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 glycosylated hemoglobin.
- History of infection with hepatitis B, hepatitis C, or human immunodeficiency virus.
- History of a psychiatric disorder that in the investigator's opinion will affect the subject's ability to participate in the study.
- History of alcohol abuse or substance abuse within the 2 years prior to Screening.
The subject is required to take or intends to continue taking any disallowed medication, any prescription medication, herbal treatment or over-the counter medication that may interfere with evaluation of the study medication, including:
- Treatment with antidiabetic agents other than study drug or metformin or sulfonylurea is not allowed within the 3 months prior to Screening and through the completion of the end-of-treatment/early termination procedures.
- Treatment with weight-loss drugs, any investigational antidiabetic drugs, or oral or systemically injected glucocorticoids is not allowed from 3 months prior to randomization through the completion of the end-of-treatment/early termination procedures.
- 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-619 or alogliptin.
- The subject has a known hypersensitivity to any compound related to SYR-619 or alogliptin.
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm 6
Arm Type
Experimental
Experimental
Experimental
Experimental
Placebo Comparator
Active Comparator
Arm Label
SYR-619 12.5 mg QD
SYR-619 50 mg QD
SYR-619 100 mg QD
SYR-619 200 mg QD
Placebo QD
Alogliptin 25 mg QD
Arm Description
Outcomes
Primary Outcome Measures
Change from baseline in glycosylated hemoglobin.
Secondary Outcome Measures
Change from baseline in glycosylated hemoglobin.
Change from baseline in fasting plasma glucose.
Change from baseline in 1,5 anhydroglucitol.
Change from baseline in proinsulin.
Change from baseline in insulin.
Change from baseline in proinsulin/insulin ratio.
Change from baseline in C-peptide.
Homeostasis model assessment insulin resistance.
Homeostasis model assessment beta-cell function.
Incidence of marked hyperglycemia (fasting plasma glucose ≥200 mg/dL [≥11.10 mmol/L]).
Incidence of rescue.
Clinical response endpoint incidence of glycosylated hemoglobin ≤6.5%.
Clinical response endpoint incidence of glycosylated hemoglobin ≤7.0%.
Clinical response endpoint incidence of glycosylated hemoglobin improvement ≥1.0%.
Clinical response endpoint incidence of glycosylated hemoglobin improvement ≥1.5%.
Clinical response endpoint incidence of glycosylated hemoglobin improvement ≥2.0%.
Fasting lipids (triglycerides, total cholesterol, high-density lipoprotein and low-density lipoprotein cholesterol).
Postprandial area under the concentration-time curve and peak 2-hour values of plasma glucose, insulin and C-peptide during a 3-hour mixed-meal tolerance test in a subset of subjects.
Plasma concentration of SYR-619.
Physical examination findings (including a clinical examination of skin and digits).
Vital sign measurements.
Body temperature measurements.
12-lead electrocardiogram tracings.
Incidence of adverse events.
Incidence of hypoglycemia (blood glucose <60 mg/dL [<3.33 mmol/L]) in the presence of symptoms or blood glucose <50 mg/dL [<2.78 mmol/L]) regardless of symptoms).
Clinical laboratory evaluations (hematology and serum chemistry).
Clinical laboratory evaluation (urinalysis).
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00763347
Brief Title
Efficacy and Safety Study of SYR-619 in Treating Subjects With Type 2 Diabetes Mellitus
Official Title
A Phase 2, Double-Blind Randomized, Placebo-Controlled, Parallel Group, Multicenter Study to Evaluate Treatment With SYR-619 in Subjects With Type 2 Diabetes
Study Type
Interventional
2. Study Status
Record Verification Date
May 2012
Overall Recruitment Status
Terminated
Why Stopped
Voluntarily terminated based on preliminary non-clinical findings.
Study Start Date
November 2006 (undefined)
Primary Completion Date
February 2007 (Actual)
Study Completion Date
February 2007 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Takeda
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
The purpose of this study is to determine the efficacy and safety of SYR-619, once daily (QD), in subjects with type 2 diabetes mellitus who have not achieved glycemic control with diet and exercise, or by taking metformin.
Detailed Description
There are approximately 19 million people in the United States who have been diagnosed with diabetes mellitus, of which 90% to 95% is type 2. The prevalence of type 2 diabetes varies among racial and ethnic populations and has been shown to correlate with age, obesity, family history, history of gestational diabetes, and physical inactivity. Over the next decade, a marked increase in the number of adults with diabetes mellitus is expected, placing an ever increasing burden on families and the health care system.
SYR-619 is an inhibitor of the dipeptidyl peptidase IV enzyme. Dipeptidyl peptidase IV is thought to be primarily responsible for the in vivo degradation of 2 peptide hormones released in response to nutrient ingestion, namely glucagon-like peptide-1 and glucose-dependent insulinotropic peptide.
The aim of this study is to evaluate the dose-response efficacy, safety and tolerability of treatment with SYR-619 in subjects with type 2 diabetes who do not previously achieve adequate glycemic control with lifestyle modification (diet/exercise) or metformin or sulfonylurea oral antidiabetic monotherapy.
Individuals who want to participate in this study will be required to provide written informed consent. Study participation is anticipated to be about 14 Weeks. Multiple procedures will occur at each visit which may include fasting, blood collection, urine collection, vital signs including sitting and standing blood pressure and pulse, body height and weight, physical examinations, electrocardiogram.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Diabetes Mellitus
Keywords
Glucose Metabolism Disorder, Dysmetabolic Syndrome, Type II Diabetes, Diabetes Mellitus, Lipoatrophic, Dyslipidemia, Drug Therapy
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
82 (Actual)
8. Arms, Groups, and Interventions
Arm Title
SYR-619 12.5 mg QD
Arm Type
Experimental
Arm Title
SYR-619 50 mg QD
Arm Type
Experimental
Arm Title
SYR-619 100 mg QD
Arm Type
Experimental
Arm Title
SYR-619 200 mg QD
Arm Type
Experimental
Arm Title
Placebo QD
Arm Type
Placebo Comparator
Arm Title
Alogliptin 25 mg QD
Arm Type
Active Comparator
Intervention Type
Drug
Intervention Name(s)
SYR-619
Intervention Description
SYR-619 12.5 mg, tablets, orally, once daily for up to 12 weeks.
Intervention Type
Drug
Intervention Name(s)
SYR-619
Intervention Description
SYR-619 50 mg, tablets, orally, once daily for up to 12 weeks.
Intervention Type
Drug
Intervention Name(s)
SYR-619
Intervention Description
SYR-619 100 mg, tablets, orally, once daily for up to 12 weeks.
Intervention Type
Drug
Intervention Name(s)
SYR-619
Intervention Description
SYR-619 200 mg, tablets, orally, once daily for up to 12 weeks.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
SYR-619 placebo-matching tablets, orally, once daily for up to 12 weeks.
Intervention Type
Drug
Intervention Name(s)
Alogliptin
Other Intervention Name(s)
SYR-322
Intervention Description
Alogliptin 25 mg, tablets, orally, once daily for up to 12 weeks.
Primary Outcome Measure Information:
Title
Change from baseline in glycosylated hemoglobin.
Time Frame
Week 12 or Final Visit..
Secondary Outcome Measure Information:
Title
Change from baseline in glycosylated hemoglobin.
Time Frame
Weeks 4, 8 and 12 or Final Visit.
Title
Change from baseline in fasting plasma glucose.
Time Frame
Weeks: 1, 2, 4, 8 and 12 or Final Visit.
Title
Change from baseline in 1,5 anhydroglucitol.
Time Frame
Weeks 2, 4, 8 and 12 or Final Visit.
Title
Change from baseline in proinsulin.
Time Frame
Weeks 4, 8 and 12 or Final Visit.
Title
Change from baseline in insulin.
Time Frame
Weeks 4, 8 and 12 or Final Visit.
Title
Change from baseline in proinsulin/insulin ratio.
Time Frame
Weeks 4, 8 and 12 or Final Visit.
Title
Change from baseline in C-peptide.
Time Frame
Weeks 4, 8 and 12 or Final Visit.
Title
Homeostasis model assessment insulin resistance.
Time Frame
Weeks 4, 8 and 12 or Final Visit.
Title
Homeostasis model assessment beta-cell function.
Time Frame
Weeks 4, 8 and 12 or Final Visit.
Title
Incidence of marked hyperglycemia (fasting plasma glucose ≥200 mg/dL [≥11.10 mmol/L]).
Time Frame
Weeks 1, 2, 4, 8 and 12 or Final Visit.
Title
Incidence of rescue.
Time Frame
Weeks 1, 2, 4, 8 and 12 or Final Visit.
Title
Clinical response endpoint incidence of glycosylated hemoglobin ≤6.5%.
Time Frame
Week 12 or Final Visit.
Title
Clinical response endpoint incidence of glycosylated hemoglobin ≤7.0%.
Time Frame
Week 12 or Final Visit.
Title
Clinical response endpoint incidence of glycosylated hemoglobin improvement ≥1.0%.
Time Frame
Week 12 or Final Visit.
Title
Clinical response endpoint incidence of glycosylated hemoglobin improvement ≥1.5%.
Time Frame
Week 12 or Final Visit.
Title
Clinical response endpoint incidence of glycosylated hemoglobin improvement ≥2.0%.
Time Frame
Week 12 or Final Visit.
Title
Fasting lipids (triglycerides, total cholesterol, high-density lipoprotein and low-density lipoprotein cholesterol).
Time Frame
Weeks 4, 8, and 12 or Final Visit.
Title
Postprandial area under the concentration-time curve and peak 2-hour values of plasma glucose, insulin and C-peptide during a 3-hour mixed-meal tolerance test in a subset of subjects.
Time Frame
Week 12 or Final Visit.
Title
Plasma concentration of SYR-619.
Time Frame
Week 8.
Title
Physical examination findings (including a clinical examination of skin and digits).
Time Frame
At All Visits
Title
Vital sign measurements.
Time Frame
At All Visits
Title
Body temperature measurements.
Time Frame
Week 12 or Final Visit.
Title
12-lead electrocardiogram tracings.
Time Frame
Week 12 or Final Visit.
Title
Incidence of adverse events.
Time Frame
At All Visits
Title
Incidence of hypoglycemia (blood glucose <60 mg/dL [<3.33 mmol/L]) in the presence of symptoms or blood glucose <50 mg/dL [<2.78 mmol/L]) regardless of symptoms).
Time Frame
At All Visits
Title
Clinical laboratory evaluations (hematology and serum chemistry).
Time Frame
At All Visits
Title
Clinical laboratory evaluation (urinalysis).
Time Frame
Week 12 or Final Visit.
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Male or female, with a historical diagnosis of type 2 diabetes mellitus.
Treatment for diabetes with either lifestyle modification or metformin or sulfonylurea alone for at least the 2 months prior to Screening; and a stable dose of either metformin or sulfonylurea for at least 12 weeks prior to randomization for subjects receiving metformin or sulfonylurea at Screening.
Those subjects receiving metformin or sulfonylurea monotherapy at randomization must have been at least 75% compliant with their metformin or sulfonylurea regimen during the run in/stabilization period, as assessed by subject diary and investigator assessment.
No treatment with antidiabetic agents other than metformin alone or sulfonylurea alone within the 3 months prior to Screening.
Glycosylated hemoglobin concentration between 7.0% and 10.0%, inclusive, and a fasting plasma glucose <275 mg/dL (<15.27 mmol/L) at the Week -1 visit.
Body mass index ≥23 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).
If regular use of other non-excluded medications, must be on a stable dose for at least the 4 weeks prior to Screening. However, as needed use of prescription or over-the-counter medications is allowed at the discretion of the investigator.
Systolic blood pressure <160 mm Hg and diastolic pressure <100 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.
Urine albumin/creatinine ratio of <1000 μg/mg (113 mg/mol) at Screening. If elevated, the subject may be rescreened within 1 week.
Thyroid-stimulating hormone level ≤ the upper limit of the normal range and the subject has normal thyroid function (clinically euthyroid)
A female subject of childbearing potential who is sexually active must agree to use adequate contraception, and must be neither pregnant nor lactating from Screening and throughout the duration of 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.
Exclusion Criteria:
Concurrently treated with combined metformin and sulfonylurea antidiabetic therapy.
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.
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.
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 glycosylated hemoglobin.
History of infection with hepatitis B, hepatitis C, or human immunodeficiency virus.
History of a psychiatric disorder that in the investigator's opinion will affect the subject's ability to participate in the study.
History of alcohol abuse or substance abuse within the 2 years prior to Screening.
The subject is required to take or intends to continue taking any disallowed medication, any prescription medication, herbal treatment or over-the counter medication that may interfere with evaluation of the study medication, including:
Treatment with antidiabetic agents other than study drug or metformin or sulfonylurea is not allowed within the 3 months prior to Screening and through the completion of the end-of-treatment/early termination procedures.
Treatment with weight-loss drugs, any investigational antidiabetic drugs, or oral or systemically injected glucocorticoids is not allowed from 3 months prior to randomization through the completion of the end-of-treatment/early termination procedures.
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-619 or alogliptin.
The subject has a known hypersensitivity to any compound related to SYR-619 or alogliptin.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
VP Biological Sciences
Organizational Affiliation
Takeda
Official's Role
Study Director
12. IPD Sharing Statement
Learn more about this trial
Efficacy and Safety Study of SYR-619 in Treating Subjects With Type 2 Diabetes Mellitus
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