Postmarketing Clinical Study on AO-128

Study Overview
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Brief Summary
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The purpose of open-label study is to evaluate the efficacy and safety of AO-128 (Voglibose) 0.6 mg/day in patients with impaired glucose tolerance (IGT) who had been non-responsive to diet therapy and exercise therapy, and follow up the progress after the end of treatment in patients who was assessed as normoglycemic.

Detailed Description
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The α-glucosidase inhibitor voglibose was developed by Takeda Pharmaceutical Co. Ltd and is one of the most commonly used oral antidiabetic agents in Japan. Voglibose is used as first-line treatment for improvement of postprandial hyperglycemia in diabetic patients with inadequate response to diet and exercise therapy and as add-on treatment to other oral antidiabetic drugs and insulin. In 2009, voglibose was approved in Japan for the management of prediabetes (IGT). This study was a single-group, multi-center, open-label study. The study period consisted of a screening period of 1 week or less, a treatment period of 96 weeks or more, and a follow-up period of 48 weeks. However, if a patient was assessed as having type 2 diabetes mellitus or normoglycemia, the treatment period was to be ended, and only those assessed as normoglycemic were to proceed to follow-up. Follow-up was also to be terminated if patients were assessed as having IGT or type 2 diabetes mellitus during follow-up.

Official Title
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Postmarketing Clinical Study on AO-128

Conditions
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Impaired Glucose Tolerance (IGT)

Intervention / Treatment
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* Drug: AO-128


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients on diet therapy and exercise therapy for 3 to 6 months prior to the start of screening, with baseline (fasting ) plasma glucose < 126 mg/dL and 2-hour plasma glucose of 140 to 199 mg/dL (revised WHO criteria) during a 75 g oral glucose tolerance test (OGTT) in the screening period Patients meeting any of 1 through 4 below: 1) Comorbid hypertension or high normal blood pressure 2) Comorbid dyslipidemia 3) Comorbid obesity 4) Patients with up to a second-degree family history of type 2 diabetes mellitus Patients with HbA1c < 6.5% in the screening period Male or female patients at least 20 years of age at the time informed consent was obtained Treatment category: Outpatient Exclusion Criteria: Patients previously diagnosed with diabetes mellitus. Patients with apparent impaired glucose metabolism or with a disease or condition potentially involving impaired glucose metabolism. Patients with serious hepatic impairment. Patients with serious renal impairment. Patients with serious cardiac, cerebrovascular, pancreatic, hematologic, or other disease. Patients with a history of intestinal obstruction or a history of laparotomy within 6 months (24 weeks) before the start of screening.

Ages Eligible for Study
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Minimum Age: 20 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AO-128 0.6 mg<br>One AO-128 0.2 mg tablet was taken orally 3 times a day before meals. | Drug: AO-128<br>* AO-128 tablet<br>* Other names: BASEN;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assessment of Diabetic Status in the Treatment Period (Type 2 Diabetes Mellitus, Normoglycemia, or Impaired Glucose Tolerance (IGT) | Frequency tabulations of the assessment of diabetic status in the treatment period (Type 2 Diabetes mellitus, normoglycemia, or IGT) were prepared in the Full Analysis Set. | Treatment period: Up to 122 weeks. Treatment was to be ended when patients were assessed as Type 2 Diabetes Mellitus or normoglycemic. | 
| Assessment of Diabetic Status in Follow-up (Type 2 Diabetes Mellitus, Normoglycemia, or IGT) | Frequency tabulations of the assessment of diabetic status in the follow-up (Type 2 Diabetes mellitus, normoglycemia, or IGT) were prepared in patients who proceeded to the follow-up in the Full Analysis Set. | Follow-up at Week 12, 24, 36, and 48 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Progression to Type 2 Diabetes Mellitus in the Treatment Period Calculated by the Kaplan-Meier Method | The cumulative progression rate (percentage of participants) was calculated by the Kaplan-Meier method for the time to progression to Type 2 Diabetes mellitus in the treatment period in the Full Analysis Set. | Day 168, 336, 504, and 672 | 
| Time to Progression to Type 2 Diabetes Mellitus in the Treatment Period Calculated Using the Cumulative Incidence Function | The cumulative progression rate (percentage of participants) was calculated using the cumulative incidence function for the time to progression to type 2 diabetes mellitus in the treatment period in the Full Analysis Set. | Day 168, 336, 504, and 672 | 
| Time to Improvement to Normoglycemia in the Treatment Period Calculated by the Kaplan-Meier Method | The cumulative progression rate (percentage of participants) was calculated by the Kaplan-Meier method for the time to improvement to normoglycemia in the treatment period in the Full Analysis Set. | Day 168, 336, 504, and 672 | 
| Time to Improvement to Normoglycemia in the Treatment Period Measured Values by the Cumulative Incidence Function | The cumulative progression rate (percentage of participants) was calculated using the cumulative incidence function for the time to improvement to normoglycemia in the treatment period in the Full Analysis Set. | Day 168, 336, 504, and 672 | 
| 2-Hour Plasma Glucose During 75 g Oral Glucose Tolerance Test (OGTT) | Summary statistics were calculated at each assessment time point for the 2-hour plasma glucose during 75 g OGTT in the Full Analysis Set. | Week 0, 24, 48, 72, 96, 120, and the end of the treatment period | 
| 2-Hour Plasma Glucose During 75 g OGTT at Follow-up | Summary statistics were calculated at each assessment time point for the 2-hour plasma glucose during 75 g OGTT in participants who proceeded to the follow-up in the Full Analysis Set. | Follow-up at week 0, 12, 24, 36, and 48 | 
| Hemoglobin A1c (HbA1c) | Summary statistics were calculated at each assessment time point for the HbA1c in the Full Analysis Set. | Week 0, 12, 24, 48, 72, 96, 120, and the end of the treatment period. | 
| HbA1c at Follow-up | Summary statistics were calculated at each assessment time point for the HbA1c in patients who proceeded to the follow-up in the Full Analysis Set. | Follow-up at Week 0, 12, 24, 36, and 48 | 
| Body Weight | Summary statistics were calculated at each assessment time point for the body weight in the Full Analysis Set. | Week 0, 12, 24, 48, 72, 96, 120, and the end of the treatment period | 
| Body Weight at Follow-up | Summary statistics were calculated at each assessment time point for the HbA1c in patients who proceeded to the follow-up in the Full Analysis Set. | Follow-up at Week 0, 12, 24, 36, and 48 |