Postmarketing Clinical Study on AO-128

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.

Study Overview

• Status: Completed
• Conditions: Impaired Glucose Tolerance (IGT)
• Intervention / Treatment: Drug: AO-128

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 197
• Phase: Phase 4

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. 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

2. 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
3. Patients with HbA1c < 6.5% in the screening period
4. Male or female patients at least 20 years of age at the time informed consent was obtained
5. Treatment category: Outpatient

Exclusion Criteria:

1. Patients previously diagnosed with diabetes mellitus.
2. Patients with apparent impaired glucose metabolism or with a disease or condition potentially involving impaired glucose metabolism.
3. Patients with serious hepatic impairment.
4. Patients with serious renal impairment.
5. Patients with serious cardiac, cerebrovascular, pancreatic, hematologic, or other disease.
6. Patients with a history of intestinal obstruction or a history of laparotomy within 6 months (24 weeks) before the start of screening.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: AO-128 0.6 mg; One AO-128 0.2 mg tablet was taken orally 3 times a day before meals.	Drug: AO-128; AO-128 tablet; Other Names: Voglibose; BASEN

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Takeda

Study record dates

Study Major Dates

• Study Start: March 1, 2010
• Primary Completion (Actual): November 1, 2012
• Study Completion (Actual): November 1, 2012

Study Registration Dates

• First Submitted: October 22, 2014
• First Submitted That Met QC Criteria: November 5, 2014
• First Posted (Estimate): November 10, 2014

Study Record Updates

• Last Update Posted (Estimate): April 9, 2015
• Last Update Submitted That Met QC Criteria: April 8, 2015
• Last Verified: April 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Hyperglycemia; Glucose Intolerance; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Glycoside Hydrolase Inhibitors; Voglibose
• Other Study ID Numbers: AO-128/OCT-910; JapicCTI-101004 (Other Identifier: JapicCTI); U1111-1163-1618 (Registry Identifier: WHO)