Impaired Glucose Tolerance (IGT)
Conditions
Brief summary
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
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.
Interventions
DRUGAO-128
AO-128 tablet
Sponsors
Takeda
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Assessment of Diabetic Status in the Treatment Period (Type 2 Diabetes Mellitus, Normoglycemia, or Impaired Glucose Tolerance (IGT) | Treatment period: Up to 122 weeks. Treatment was to be ended when patients were assessed as Type 2 Diabetes Mellitus or normoglycemic. | 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. |
| Assessment of Diabetic Status in Follow-up (Type 2 Diabetes Mellitus, Normoglycemia, or IGT) | Follow-up at Week 12, 24, 36, and 48 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Improvement to Normoglycemia in the Treatment Period Calculated by the Kaplan-Meier Method | Day 168, 336, 504, and 672 | 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. |
| Time to Improvement to Normoglycemia in the Treatment Period Measured Values by the Cumulative Incidence Function | Day 168, 336, 504, and 672 | 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. |
| 2-Hour Plasma Glucose During 75 g Oral Glucose Tolerance Test (OGTT) | Week 0, 24, 48, 72, 96, 120, and the end of the treatment period | Summary statistics were calculated at each assessment time point for the 2-hour plasma glucose during 75 g OGTT in the Full Analysis Set. |
| 2-Hour Plasma Glucose During 75 g OGTT at Follow-up | Follow-up at week 0, 12, 24, 36, and 48 | 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. |
| Time to Progression to Type 2 Diabetes Mellitus in the Treatment Period Calculated by the Kaplan-Meier Method | Day 168, 336, 504, and 672 | 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. |
| HbA1c at Follow-up | Follow-up at Week 0, 12, 24, 36, and 48 | 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. |
| Body Weight | Week 0, 12, 24, 48, 72, 96, 120, and the end of the treatment period | Summary statistics were calculated at each assessment time point for the body weight in the Full Analysis Set. |
| Body Weight at Follow-up | Follow-up at Week 0, 12, 24, 36, and 48 | 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. |
| Hemoglobin A1c (HbA1c) | Week 0, 12, 24, 48, 72, 96, 120, and the end of the treatment period. | Summary statistics were calculated at each assessment time point for the HbA1c in the Full Analysis Set. |
| Time to Progression to Type 2 Diabetes Mellitus in the Treatment Period Calculated Using the Cumulative Incidence Function | Day 168, 336, 504, and 672 | 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. |
Participant flow
Recruitment details
Participants took part in the study at 30 investigative sites in Japan from 9 March 2010 to 15 November 2012.
Pre-assignment details
Participants with impaired glucose tolerance (IGT) who had been non-responsive to diet therapy and exercise therapy receive one AO-128 0.2 mg tablet orally 3 times a day before meals.
Participants by arm
| Arm | Count |
|---|---|
| AO-128 0.6 mg One AO-128 0.2 mg tablet was taken orally 3 times a day before meals. | 197 |
| Total | 197 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Follow-up | Lost to Follow-up | 1 |
| Follow-up | Voluntary Withdrawal | 2 |
| Treatment Period | Adverse Event | 17 |
| Treatment Period | Voluntary Withdrawal | 10 |
Baseline characteristics
| Characteristic | AO-128 0.6 mg |
|---|---|
| Age, Continuous | 59.2 years STANDARD_DEVIATION 9.35 |
| Age, Customized <65 years | 137 participants |
| Age, Customized ≥65 years | 60 participants |
| Region of Enrollment Japan | 197 participants |
| Sex: Female, Male Female | 68 Participants |
| Sex: Female, Male Male | 129 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 165 / 197 |
| serious Total, serious adverse events | 15 / 197 |
Outcome results
Primary
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.
Time frame: Follow-up at Week 12, 24, 36, and 48
Population: Participants from the Full Analysis Set, all participants who received at least 1 dose of open-label study drug, and continued to Follow-up.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| AO-128 0.6 mg | Assessment of Diabetic Status in Follow-up (Type 2 Diabetes Mellitus, Normoglycemia, or IGT) | Type 2 Diabetes mellitus | 3 participants |
| AO-128 0.6 mg | Assessment of Diabetic Status in Follow-up (Type 2 Diabetes Mellitus, Normoglycemia, or IGT) | Normoglycemia | 9 participants |
| AO-128 0.6 mg | Assessment of Diabetic Status in Follow-up (Type 2 Diabetes Mellitus, Normoglycemia, or IGT) | IGT | 94 participants |
Primary
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.
Time frame: Treatment period: Up to 122 weeks. Treatment was to be ended when patients were assessed as Type 2 Diabetes Mellitus or normoglycemic.
Population: Full Analysis Set - All participants who received at least 1 dose of open-label study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| AO-128 0.6 mg | Assessment of Diabetic Status in the Treatment Period (Type 2 Diabetes Mellitus, Normoglycemia, or Impaired Glucose Tolerance (IGT) | Type 2 Diabetes mellitus | 25 participants |
| AO-128 0.6 mg | Assessment of Diabetic Status in the Treatment Period (Type 2 Diabetes Mellitus, Normoglycemia, or Impaired Glucose Tolerance (IGT) | Normoglycemia | 106 participants |
| AO-128 0.6 mg | Assessment of Diabetic Status in the Treatment Period (Type 2 Diabetes Mellitus, Normoglycemia, or Impaired Glucose Tolerance (IGT) | IGT | 66 participants |
Secondary
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.
Time frame: Follow-up at week 0, 12, 24, 36, and 48
Population: Participants from the Full Analysis Set, all participants who received at least 1 dose of open-label study drug, and continued to Follow-up.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| AO-128 0.6 mg | 2-Hour Plasma Glucose During 75 g OGTT at Follow-up | Follow-up at Week 0 | 119.4 mg/dL | Standard Deviation 15.82 |
| AO-128 0.6 mg | 2-Hour Plasma Glucose During 75 g OGTT at Follow-up | Follow-up at Week 12 | 148.3 mg/dL | Standard Deviation 35.26 |
| AO-128 0.6 mg | 2-Hour Plasma Glucose During 75 g OGTT at Follow-up | Follow-up at Week 24 | 147.9 mg/dL | Standard Deviation 29.69 |
| AO-128 0.6 mg | 2-Hour Plasma Glucose During 75 g OGTT at Follow-up | Follow-up at Week 36 | 145.9 mg/dL | Standard Deviation 18.94 |
| AO-128 0.6 mg | 2-Hour Plasma Glucose During 75 g OGTT at Follow-up | Follow-up at Week 48 | 138.3 mg/dL | Standard Deviation 20.06 |
Secondary
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.
Time frame: Week 0, 24, 48, 72, 96, 120, and the end of the treatment period
Population: Full Analysis Set - All participants who received at least 1 dose of open-label study drug.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| AO-128 0.6 mg | 2-Hour Plasma Glucose During 75 g Oral Glucose Tolerance Test (OGTT) | Week 0 | 166.7 mg/dL | Standard Deviation 17.34 |
| AO-128 0.6 mg | 2-Hour Plasma Glucose During 75 g Oral Glucose Tolerance Test (OGTT) | Week 24 | 148.0 mg/dL | Standard Deviation 34.3 |
| AO-128 0.6 mg | 2-Hour Plasma Glucose During 75 g Oral Glucose Tolerance Test (OGTT) | Week 48 | 153.2 mg/dL | Standard Deviation 36.58 |
| AO-128 0.6 mg | 2-Hour Plasma Glucose During 75 g Oral Glucose Tolerance Test (OGTT) | Week 72 | 155.6 mg/dL | Standard Deviation 36.77 |
| AO-128 0.6 mg | 2-Hour Plasma Glucose During 75 g Oral Glucose Tolerance Test (OGTT) | Week 96 | 155.6 mg/dL | Standard Deviation 33.17 |
| AO-128 0.6 mg | 2-Hour Plasma Glucose During 75 g Oral Glucose Tolerance Test (OGTT) | Week 120 | 163.2 mg/dL | Standard Deviation 31.89 |
| AO-128 0.6 mg | 2-Hour Plasma Glucose During 75 g Oral Glucose Tolerance Test (OGTT) | The end of the treatment period | 142.8 mg/dL | Standard Deviation 37.73 |
Secondary
Body Weight
Summary statistics were calculated at each assessment time point for the body weight in the Full Analysis Set.
Time frame: Week 0, 12, 24, 48, 72, 96, 120, and the end of the treatment period
Population: Full Analysis Set - All participants who received at least 1 dose of open-label study drug.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| AO-128 0.6 mg | Body Weight | The end of the treatment period | 68.96 kg | Standard Deviation 13.892 |
| AO-128 0.6 mg | Body Weight | Week 0 | 70.74 kg | Standard Deviation 13.708 |
| AO-128 0.6 mg | Body Weight | Week 12 | 69.74 kg | Standard Deviation 13.659 |
| AO-128 0.6 mg | Body Weight | Week 24 | 69.91 kg | Standard Deviation 13.658 |
| AO-128 0.6 mg | Body Weight | Week 48 | 69.25 kg | Standard Deviation 13.632 |
| AO-128 0.6 mg | Body Weight | Week 72 | 70.03 kg | Standard Deviation 13.955 |
| AO-128 0.6 mg | Body Weight | Week 96 | 69.25 kg | Standard Deviation 14.484 |
| AO-128 0.6 mg | Body Weight | Week 120 | 68.82 kg | Standard Deviation 14.835 |
Secondary
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.
Time frame: Follow-up at Week 0, 12, 24, 36, and 48
Population: Participants from the Full Analysis Set, all participants who received at least 1 dose of open-label study drug, and continued to Follow-up.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| AO-128 0.6 mg | Body Weight at Follow-up | Follow-up at Week 0 | 67.60 kg | Standard Deviation 13.023 |
| AO-128 0.6 mg | Body Weight at Follow-up | Follow-up at Week 12 | 67.76 kg | Standard Deviation 13.035 |
| AO-128 0.6 mg | Body Weight at Follow-up | Follow-up at Week 24 | 68.87 kg | Standard Deviation 11.703 |
| AO-128 0.6 mg | Body Weight at Follow-up | Follow-up at Week 36 | 70.13 kg | Standard Deviation 11.754 |
| AO-128 0.6 mg | Body Weight at Follow-up | Follow-up at Week 48 | 68.72 kg | Standard Deviation 13.844 |
Secondary
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.
Time frame: Follow-up at Week 0, 12, 24, 36, and 48
Population: Participants from the Full Analysis Set, all participants who received at least 1 dose of open-label study drug, and continued to Follow-up.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| AO-128 0.6 mg | HbA1c at Follow-up | Follow-up at Week 12 | 5.27 percent | Standard Deviation 0.33 |
| AO-128 0.6 mg | HbA1c at Follow-up | Follow-up at Week 24 | 5.26 percent | Standard Deviation 0.326 |
| AO-128 0.6 mg | HbA1c at Follow-up | Follow-up at Week 36 | 5.20 percent | Standard Deviation 0.301 |
| AO-128 0.6 mg | HbA1c at Follow-up | Follow-up at Week 0 | 5.23 percent | Standard Deviation 0.292 |
| AO-128 0.6 mg | HbA1c at Follow-up | Follow-up at Week 48 | 5.28 percent | Standard Deviation 0.26 |
Secondary
Hemoglobin A1c (HbA1c)
Summary statistics were calculated at each assessment time point for the HbA1c in the Full Analysis Set.
Time frame: Week 0, 12, 24, 48, 72, 96, 120, and the end of the treatment period.
Population: Full Analysis Set - All participants who received at least 1 dose of open-label study drug.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| AO-128 0.6 mg | Hemoglobin A1c (HbA1c) | The end of the treatment period | 5.35 percent | Standard Deviation 0.323 |
| AO-128 0.6 mg | Hemoglobin A1c (HbA1c) | Week 0 | 5.45 percent | Standard Deviation 0.331 |
| AO-128 0.6 mg | Hemoglobin A1c (HbA1c) | Week 12 | 5.35 percent | Standard Deviation 0.305 |
| AO-128 0.6 mg | Hemoglobin A1c (HbA1c) | Week 24 | 5.30 percent | Standard Deviation 0.302 |
| AO-128 0.6 mg | Hemoglobin A1c (HbA1c) | Week 48 | 5.37 percent | Standard Deviation 0.317 |
| AO-128 0.6 mg | Hemoglobin A1c (HbA1c) | Week 72 | 5.34 percent | Standard Deviation 0.285 |
| AO-128 0.6 mg | Hemoglobin A1c (HbA1c) | Week 96 | 5.41 percent | Standard Deviation 0.269 |
| AO-128 0.6 mg | Hemoglobin A1c (HbA1c) | Week 120 | 5.45 percent | Standard Deviation 0.256 |
Secondary
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.
Time frame: Day 168, 336, 504, and 672
Population: Full Analysis Set - All participants who received at least 1 dose of open-label study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| AO-128 0.6 mg | Time to Improvement to Normoglycemia in the Treatment Period Calculated by the Kaplan-Meier Method | Day 168 | 18.9 percentage of participants |
| AO-128 0.6 mg | Time to Improvement to Normoglycemia in the Treatment Period Calculated by the Kaplan-Meier Method | Day 336 | 37.5 percentage of participants |
| AO-128 0.6 mg | Time to Improvement to Normoglycemia in the Treatment Period Calculated by the Kaplan-Meier Method | Day 504 | 50.2 percentage of participants |
| AO-128 0.6 mg | Time to Improvement to Normoglycemia in the Treatment Period Calculated by the Kaplan-Meier Method | Day 672 | 60.3 percentage of participants |
Secondary
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.
Time frame: Day 168, 336, 504, and 672
Population: Full Analysis Set - All participants who received at least 1 dose of open-label study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| AO-128 0.6 mg | Time to Improvement to Normoglycemia in the Treatment Period Measured Values by the Cumulative Incidence Function | Day 168 | 18.9 percentage of participants |
| AO-128 0.6 mg | Time to Improvement to Normoglycemia in the Treatment Period Measured Values by the Cumulative Incidence Function | Day 336 | 36.9 percentage of participants |
| AO-128 0.6 mg | Time to Improvement to Normoglycemia in the Treatment Period Measured Values by the Cumulative Incidence Function | Day 504 | 48.4 percentage of participants |
| AO-128 0.6 mg | Time to Improvement to Normoglycemia in the Treatment Period Measured Values by the Cumulative Incidence Function | Day 672 | 57.1 percentage of participants |
Secondary
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.
Time frame: Day 168, 336, 504, and 672
Population: Full Analysis Set - All participants who received at least 1 dose of open-label study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| AO-128 0.6 mg | Time to Progression to Type 2 Diabetes Mellitus in the Treatment Period Calculated by the Kaplan-Meier Method | Day 168 | 0.0 percentage of participants |
| AO-128 0.6 mg | Time to Progression to Type 2 Diabetes Mellitus in the Treatment Period Calculated by the Kaplan-Meier Method | Day 336 | 4.4 percentage of participants |
| AO-128 0.6 mg | Time to Progression to Type 2 Diabetes Mellitus in the Treatment Period Calculated by the Kaplan-Meier Method | Day 504 | 10.2 percentage of participants |
| AO-128 0.6 mg | Time to Progression to Type 2 Diabetes Mellitus in the Treatment Period Calculated by the Kaplan-Meier Method | Day 672 | 16.9 percentage of participants |
Secondary
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.
Time frame: Day 168, 336, 504, and 672
Population: Full Analysis Set - All participants who received at least 1 dose of open-label study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| AO-128 0.6 mg | Time to Progression to Type 2 Diabetes Mellitus in the Treatment Period Calculated Using the Cumulative Incidence Function | Day 168 | 0.0 percentage of participants |
| AO-128 0.6 mg | Time to Progression to Type 2 Diabetes Mellitus in the Treatment Period Calculated Using the Cumulative Incidence Function | Day 336 | 3.3 percentage of participants |
| AO-128 0.6 mg | Time to Progression to Type 2 Diabetes Mellitus in the Treatment Period Calculated Using the Cumulative Incidence Function | Day 504 | 6.9 percentage of participants |
| AO-128 0.6 mg | Time to Progression to Type 2 Diabetes Mellitus in the Treatment Period Calculated Using the Cumulative Incidence Function | Day 672 | 10.0 percentage of participants |