The purpose of this study was to evaluate the efficacy and safety of 24-week treatment with metformin hydrochloride 500 mg once daily added on to alogliptin (SYR-322) 25 mg in type 2 diabetic patients with inadequate glycemic control despite treatment with alogliptin 25 mg in addition to diet and exercise therapy.
The drugs being tested in this study are called alogliptin and metformin hydrochloride. Alogliptin in combination with metformin hydrochloride was being tested to treat people who have Type 2 diabetes mellitus (T2DM) with inadequate glycemic control despite treatment with alogliptin in addition to diet and exercise. This study looked at the efficacy and safety of alogliptin 25 mg once daily (QD) + metformin hydrochloride 500 mg QD compared to alogliptin 25 mg QD + metformin hydrochloride 250 mg twice daily (BID) and alogliptin 25 mg QD administered alone. The study enrolled 374 patients. Participants were randomly assigned (by chance, like flipping a coin) to one of the three treatment groups-which remained undisclosed to the patient and study doctor during the study (unless there was an urgent medical need): * Alogliptin 25 mg QD + metformin hydrochloride 500 mg QD * Alogliptin 25 mg QD + metformin hydrochloride 250 mg BID * Alogliptin 25 mg QD This multi-center trial was conducted in Japan. The overall time to participate in this study was 36 weeks (12-week screening period and 24-week treatment period). Participants made multiple visits to the clinic including a final visit 24 weeks after the start of study medication.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
374
Alogliptin tablets
Metformin hydrochloride tablets
Metformin hydrochloride placebo-matching tablets
Unnamed facility
Nagoya, Aichi-ken, Japan
Unnamed facility
Chiba, Chiba, Japan
Unnamed facility
Fukuoka, Fukuoka, Japan
Unnamed facility
Kitakyushu-shi, Fukuoka, Japan
Unnamed facility
Kurume-shi, Fukuoka, Japan
Unnamed facility
Aki-gun, Hiroshima, Japan
Unnamed facility
Hiroshima, Hiroshima, Japan
Unnamed facility
Koga-shi, Ibaraki, Japan
Unnamed facility
Mito, Ibaraki, Japan
Unnamed facility
Tushiura-shi, Ibaraki, Japan
...and 17 more locations
Change From Baseline in Glycosylated Hemoglobin A1c (HbA1c) National Glycohemoglobin Standardization Program (NGSP) at the End of Treatment (EOT) Period
The change in the value of HbA1c (NGSP) (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) collected at End of Treatment Period relative to Baseline. A negative change from Baseline indicates improvement. An Analysis of Covariate (ANCOVA) model with change from Baseline as a dependent variable and Baseline and treatment as independent variables was used for main analyses.
Time frame: Baseline and End of Treatment (EOT) (Up to Week 24)
Change From Baseline in HbA1c (NGSP)
The change in the value of HbA1c (NGSP) (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) collected at Weeks 2, 4, 8, 12, 16, 20, 24, and EOT relative to Baseline. A negative change from Baseline indicates improvement.
Time frame: Baseline and Weeks 2, 4, 8, 12, 16, 20, 24 and EOT (Up to Week 24)
HbA1c (NGSP)
The value of HbA1c (NGSP) (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) collected at Baseline and Weeks 2, 4, 8, 12, 16, 20, 24, and EOT.
Time frame: Baseline and Weeks 2, 4, 8, 12, 16, 20, 24 and EOT (Up to Week 24)
Percentage of Participants Achieving Target HbA1c (NGSP) Levels at the EOT Period
HbA1c (NGSP) is the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound. The percentage of participants with HbA1c levels of ≥6.0, ≥7.0 and ≥8.0 at the end of Screening (Baseline) with change to target values \<6.0, \<7.0 and \<8.0 respectively at EOT.
Time frame: Baseline and EOT (Up to Week 24)
Change From Baseline in Fasting Blood Glucose
The change in the value of the fasting plasma glucose collected at Weeks 2, 4, 8, 12, 16, 20 and 24 relative to Baseline. A negative change from Baseline indicates improvement.
Time frame: Baseline and Weeks 2, 4, 8, 12, 16, 20, 24 and EOT (Up to Week 24)
Fasting Blood Glucose
The value of the fasting plasma glucose collected at Baseline and Weeks 2, 4, 8, 12, 16, 20, 24 and EOT.
Time frame: Baseline and Weeks 2, 4, 8, 12, 16, 20, 24 and EOT (Up to Week 24)
Percentage of Participants With Treatment-Emergent Adverse Events (TEAE)
An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (example, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. A treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug.
Time frame: 24 Weeks
Percentage of Participants With TEAEs Categorized Into Investigations System Organ Class (SOC) Related to Chemistry, Hematology or Urinalysis
The percentage of participants with any clinically relevant safety laboratory changes (chemistry, hematology and urinalysis) collected throughout study and recorded as AEs.
Time frame: 24 Weeks
Percentage of Participants With TEAEs Related to Vital Signs
Vital signs included sitting systolic and diastolic blood pressures (mmHg) (measured after resting for ≥ 5 minutes) and pulse rate (beats per minute \[bpm\]).
Time frame: 24 Weeks
Number of Participants Who Had Clinically Relevant Changes in 12-Lead Electrocardiogram (ECG) Findings
Number of participants who had ECG findings changed from "normal" or "abnormal but not clinically relevant" at Baseline to "abnormal and clinically relevant".
Time frame: Baseline and Weeks 12 and 24
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