Efficacy and Safety of Voglibose Compared With Acarbose in Participants With Type 2 Diabetes

A Randomized, Open-label, Non-inferiority Study to Compare the Efficacy and Safety of Voglibose and Acarbose in Patients With Type 2 Diabetes Mellitus With Poor Control of Metformin

Status

Completed

Phases

Phase 4

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT02049814

Enrollment

494

Registered

2014-01-30

Start date

2014-05-09

Completion date

2016-06-28

Last updated

2019-03-13

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Type 2 Diabetes Mellitus

Keywords

Drug therapy

Brief summary

The primary purpose of this study is to evaluate the efficacy of voglibose versus acarbose combined with metformin in participants with type 2 diabetes mellitus (T2DM) by evaluating levels of glycosylated hemoglobin.

Detailed description

The drug being tested in this study is called voglibose. Voglibose is being tested to treat type 2 diabetes in people who have diabetes that is inadequately controlled on metformin alone. This study will look at glycemic control in people who take voglibose. The study will enroll 494 patients. All participants will be enrolled in a 2-week screening phase and a metformin run-in phase. Eligible participants will be randomly assigned (by chance, like flipping a coin) to one of the two treatment groups: * Metformin and Voglibose 0.2 mg * Metformin and Acarbose 50 mg All participants will be asked to take their current dose of metformin tablets and either voglibose or acarbose tablets three times a day throughout the study. This multi-center trial will be conducted in China. The overall time to participate in this study is up to 20 weeks and participants will make 8 visits to the clinic.

Interventions

DRUGMetformin

Metformin tablets

DRUGVoglibose

Voglibose tablets

DRUGAcarbose

Acarbose tablets

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to 75 Years

Healthy volunteers

Inclusion criteria

1. Has a historical diagnosis of type 2 diabetes mellitus (T2DM) for at least 6 months prior to the screening visit (V1). 2. Is male or female and aged from 18 to 75 years, inclusively. 3. Has a body mass index (BMI) between 20 and 45 kg/m\^2, inclusively. 4. Is experiencing inadequate glycemic control with a glycosylated hemoglobin (HbA1c) concentration between 7.0% and 10.0%, inclusively. 5. Has been treated with Metformin for at least 3 months and at a stable dose (≥1000 mg/day) for at least 8 weeks prior to Screening, unless there is documentation that the participant's current dose is his or her maximum tolerated dose (MTD) and MTD is ≤1000 mg/day. 6. Keeps constant body weight with fluctuation range no more than 10% over for at least 3 months before screening. 7. Hemoglobin levels of the participant are ≥12 g/dL (≥120 g/L) in male and≥ 10 g/dL (≥100 g/L) in female at screening visit. 8. Male serum creatinine \<1.5 mg/dL and female serum creatinine \<1.4 mg/dL, or estimated glomerular filtration rate (eGFR) \>60 ml/min/1.73m\^2 based on calculation using the Modification of Diet in Renal Disease (MDRD) approximation at Screening. 9. In the opinion of the investigator, the participant is capable of understanding and complying with protocol requirements. 10. The participant or, when applicable, the participant's legally acceptable representative signs and dates a written informed consent form and any required privacy authorization prior to the initiation of any study procedures.

Exclusion criteria

1. Type 1 diabetes mellitus. 2. Has received insulin, voglibose, acarbose or other oral hypoglycemic drugs (except Metformin) for accumulative total of more than 7 days within the latest 3 months prior to Visit 1. 3. Has a history of cardiovascular disease: acute myocardial infarction, class III or IV heart failure, or cerebrovascular accident (stroke) within the latest 3 months prior to Visit 1. 4. The participant's liver function is damaged and has a significant clinical sign or symptom of hepatopathy, acute or chronic hepatitis, or the value of alanine aminotransferase (ALT) or aspartate aminotransferase (AST) is 3 times more than the upper limit of normal level at Visit 1. 5. Has an active proliferative retinopathy or macular degeneration that need to have an urgent treatment in the opinion of investigators. 6. Has a frequent attack of hypoglycemia or loses consciousness due to hypoglycemia in the opinion of investigators. 7. Has one or more times ketoacidosis or hyperosmotic status/coma. 8. Is receiving long-term (\>14days) systemic glucocorticoid treatment (except the medicine: local, intraocular, inhalation or via the nose) or has received such treatment for 4 weeks at Visit 1. 9. Has a hematopathy (e.g. hemolytic anemia, drepanocytosis) that may interfere with the HbA1c test. 10. Has other liabilities (e.g. drug abuse, alcoholism or mental disorder) that may hinder the participant to follow and complete the study. 11. Has participated in another clinical study within the past 90 days or has received any investigational compound within 30 days prior to randomization. 12. Is unsuitable for this study in the opinion of investigators. 13. Has a disease need to use other taboo or caution drugs that is not listed in this study. 14. If female, is pregnant or lactating or intending to become pregnant before, during, or within 30 days after participating in this study.

Design outcomes

Primary

Measure	Time frame	Description
Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 12	Baseline, Week 12	The change in the value of glycosylated hemoglobin (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) collected at week 12 or final visit relative to baseline.

Secondary

Measure	Time frame	Description
Change From Baseline in Fasting Blood Glucose Over Time	Baseline, Weeks 6 and 12	The change between the fasting blood glucose value collected at weeks 6 and 12 or final visit relative to baseline.
Change From Baseline in Postprandial Plasma Glucose (PPG) Over Time	1 and 2 hours after meal at Baseline, Weeks 6 and 12	The change between the value of glucose after 1 and 2 hours of meal, measured by the meal tolerance test collected at Weeks 6 and 12 or relative to baseline.
Change From Baseline in Fasting Insulin at Week 12	Baseline, Week 12	The change between the fasting insulin value collected at week 12 or final visit relative to baseline.
Change From Baseline in Postprandial Serum Insulin at Week 12	1 and 2 hours after meal at Baseline and Week 12	The change from Baseline in postprandial serum insulin, after 1 and 2 hours of meal collected at Week 12 relative to baseline.
Change From Baseline in HbA1c at Week 6	Baseline and Week 6	The change in the value of glycosylated hemoglobin (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) collected at week 6 relative to baseline.
Change From Baseline in Postprandial Serum Glucagon at Week 12	1 and 2 hours after meal at Baseline and Week 12	The change from Baseline in postprandial serum glucagon, after 1 and 2 hours of meal collected at Week 12 relative to baseline.
Change From Baseline in Calculated Homeostatic Model Assessment Insulin Resistance (HOMA IR) at Week 12	Baseline, Week 12	The change between the value of HOMA-IR collected at Week 12 and HOMA-IR collected at Baseline. HOMA IR measures insulin resistance based on fasting glucose and insulin measurements: HOMA IR = fasting plasma insulin (µIU/mL) \* fasting plasma glucose (mmol/L) / 22.5. A higher number indicates a greater insulin resistance.
Change From Baseline in Insulin Homeostatic Model Assessment Beta Cell Function (HOMA β) at Week 12	Baseline, Week 12	The change between the value of HOMA-beta cell function collected at Week 12 and HOMA-beta cell function collected at Baseline. The homeostatic model assessment estimates steady state beta cell function as a percentage of a normal reference population (%B). HOMA %B = 20 \* insulin (µIU/mL) / fasting plasma glucose (mmol/L) - 3.5.
Change From Baseline in Body Weight Over Time	Baseline, Weeks 2, 6 and 12	The change between body weight at weeks 2, 6 and 12 or relative to baseline.
Change From Baseline in Fasting Glucagon at Week 12	Baseline, Week 12	The change between the fasting glucagon value collected at week 12 or final visit relative to baseline.

Countries

China

Participant flow

Recruitment details

Participants took part in the study at 22 investigative sites in China from 09 May 2014 to 28 June 2016.

Pre-assignment details

Participants with a diagnosis of type 2 diabetes mellitus (T2DM) were enrolled in 1:1 to receive voglibose combined with metformin or acarbose combined with metformin.

Participants by arm

Arm	Count
Metformin + Voglibose 0.2 mg Metformin tablets, at the maximum tolerated dose ≥1000 mg/day, orally, for 12 weeks, in addition to voglibose 0.2 mg, tablets, orally, three times daily, for Weeks 1 and 2, followed by voglibose 0.3 mg, tablets, orally, three times daily, Weeks 3 through 12.	236
Metformin + Acarbose 50 mg Metformin tablets, at the maximum tolerated dose ≥1000 mg/day, orally, for 12 weeks, in addition to acarbose 50 mg, tablets, orally, three times daily, Weeks 1 and 2, then acarbose 100 mg, tablets, orally, three times daily, Weeks 3 through 12.	233
Total	469

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Lost to Follow-up	2	3
Overall Study	Pregnancy	1	0
Overall Study	Pretreatment event/Adverse Event (AE)	8	5
Overall Study	Reason not Specified	4	3
Overall Study	Serious Protocol Violation	5	7
Overall Study	Study Termination	0	1
Overall Study	Voluntary withdrawal	9	8

Baseline characteristics

Characteristic	Metformin + Acarbose 50 mg	Total	Metformin + Voglibose 0.2 mg
Age, Continuous	54.82 years STANDARD_DEVIATION 9.386	54.62 years STANDARD_DEVIATION 9.305	54.41 years STANDARD_DEVIATION 9.239
Baseline Diastolic Blood Pressure (DBP)	77.7 mmHg STANDARD_DEVIATION 8.28	77.1 mmHg STANDARD_DEVIATION 8	76.5 mmHg STANDARD_DEVIATION 7.69
Baseline Pulse	75.4 bpm STANDARD_DEVIATION 8.47	74.9 bpm STANDARD_DEVIATION 8.12	74.3 bpm STANDARD_DEVIATION 7.73
Baseline Systolic Blood Pressure (SBP)	127.5 mmHg STANDARD_DEVIATION 12.69	126.8 mmHg STANDARD_DEVIATION 12.46	126.2 mmHg STANDARD_DEVIATION 12.22
Baseline Temperature	36.4 °C STANDARD_DEVIATION 0.25	36.3 °C STANDARD_DEVIATION 0.26	36.3 °C STANDARD_DEVIATION 0.27
Baseline Weight	72.0 kg STANDARD_DEVIATION 12.09	71.8 kg STANDARD_DEVIATION 11.87	71.6 kg STANDARD_DEVIATION 11.68
Body Mass Index	26.4 kg/m^2 STANDARD_DEVIATION 3.63	26.4 kg/m^2 STANDARD_DEVIATION 3.45	26.4 kg/m^2 STANDARD_DEVIATION 3.27
Height	165.2 cm STANDARD_DEVIATION 8.07	165.0 cm STANDARD_DEVIATION 8.05	164.8 cm STANDARD_DEVIATION 8.05
Race/Ethnicity, Customized Ethnic Chinese	233 participants	469 participants	236 participants
Region of Enrollment China	233 participants	469 participants	236 participants
Sex: Female, Male Female	108 Participants	222 Participants	114 Participants
Sex: Female, Male Male	125 Participants	247 Participants	122 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	— / —	— / —
other Total, other adverse events	38 / 248	41 / 245
serious Total, serious adverse events	3 / 248	5 / 245

Outcome results

Primary

Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 12

The change in the value of glycosylated hemoglobin (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) collected at week 12 or final visit relative to baseline.

Time frame: Baseline, Week 12

Population: Per Protocol Set (PPS) is a subset of FAS, including participants who completed treatment as was prescribed in protocol and had no important protocol deviation.

Arm	Measure	Value (LEAST_SQUARES_MEAN)	Dispersion
Metformin + Voglibose 0.2 mg	Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 12	-0.6982 percentage of glycated hemoglobin	Standard Error 0.0742
Metformin + Acarbose 50 mg	Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 12	-0.9335 percentage of glycated hemoglobin	Standard Error 0.0764

p-value: 0.0001Paired t-test

Secondary