Type 2 Diabetes MellitusPhase 4NCT04349696
Pharmacokinetic and Pharmacodynamic Study of Glufast Tablets 10mg(Mitiglinide)
A Phase 4 study testing Mitiglinide in people with Type 2 Diabetes Mellitus and Liver Dysfunction, run by Orient Europharma Co., Ltd. at 2 sites in Taiwan.
Trial summary
This clinical trial is designed to assess the effect of hepatic impairment on the pharmacokinetic and pharmacodynamic of glufast tablets 10 mg. Read more about this study
- Who is it for?
- Ages 20 to 75 years
- Conditions the study is for
- Type 2 Diabetes Mellitus, Liver Dysfunction
- What is being tested?
- Mitiglinide
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 16 participants
- Where
- 2 sitesTaiwan
- Study dates
- 11 Feb 2014to Apr 2018
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 20 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Subjects between 20-75 years of age, inclusive.
- Body mass index (BMI) values within 20-35 kg/m2.
- Diagnosed as type 2 diabetes mellitus and have fasting plasma glucose (FPG) less than 200 mg/dL at screen visit (for subjects under antidiabetic treatment).
- Having 2-hour postprandial glucose (PPG) level higher than or equal to 200 mg/dL at screen visit (for subjects who are antidiabetic treatment-naïve).
- Having fasting plasma glucose (FPG) higher than or equal to 126 mg/dL and less than 200 mg/dL at screen visit (for subjects who are antidiabetic treatment-naïve).
- Having been treated with dietary and exercise therapy alone or with a stable regimen for diabetes, including mitiglinide, α-glucosidase inhibitors (such as acarbose and QPS Taiwan Protocol #: OEP-P2012-01 Version: 7.0 Confidential Page 19 of 32 miglitol), metformin, sulfonylureas, DPP-IV inhibitors, thiazolidinediones (such as pioglitazone and rosiglitazone), insulin preparations or with oral antidiabetic agents in combination with insulin preparations.
Show all 9Show fewer
- Have signed the written informed consent to participate in the study.
- For patients with normal hepatic function (Arm 1): characterized as normal hepatic function with laboratory tests, such as AST (SGOT), ALT (SGPT), -GT, alkaline phosphatase, total bilirubin and albumin, within the acceptable range or results with minor deviations determined to be not clinically significant by the investigator.
- For patients with moderate impaired hepatic function (Arm 2): patients who have been diagnosed as liver cirrhosis and have Child-Pugh system point between 7 and 9 within 3 months prior to screen visit or who have Child-Pugh system point between 7 and 9 during screening period.
Who cannot join
- Diagnosed as Type 1 (insulin-dependent) diabetes mellitus.
- Having 1-hour PPG or 2-hour PPG levels > 350 mg/dL at screen visit.
- History of diabetic ketoacidosis with or without coma.
- With unstable or rapidly progressive diabetic proliferative retinopathy or rapidly progressive diabetic neuropathy under investigator's judgment.
- Having clinically significant renal disease or dysfunction (e.g. serum creatinine >1.6 mg/dL) and concurrent anemia.
- Congestive heart failure (function class III to IV) or myocardial infarction within past 6 months.
Show all 20Show fewer
- Recent history of drug or alcohol addiction or abuse.
- History of allergic response(s) to mitiglinide or related drugs.
- Pregnant or lactating women or women of childbearing potential whom were not practicing a reliable form of birth control.
- Receiving any investigational drug within one month prior to screen visit.
- Taking high-dose sulfonylureas (e.g. taking doses exceeding 5 mg/day of glibenclamide or 80 mg/day of gliclazide or 4 mg/day of glimepiride or 5 mg/day glipizide).
- Any clinical condition or significant concurrent disease judged by the investigator to complicate the evaluation of the study treatment.
- Patients with normal hepatic function (Arm 1):
- A positive test for hepatitis B surface antigen or positive hepatitis C antibody.
- Presence of liver cirrhosis or liver carcinoma detected by hepatic ultrasound and deemed ineligible in the investigator's judgment.
- Patients with moderate impaired hepatic function (Arm 2):
- Having acute liver disease caused by infection or drug toxicity within one month prior to screen visit.
- History of liver transplantation.
- Having severe portal hypertension within one month prior to screen visit.
- Having fluctuating or rapidly deteriorating hepatic function based on clinical signs or laboratory tests during the screening period
Trial locations and contacts
2 sites in 1 country.
Taiwan2 sites
Chiayi Chang Gung Memorial Hospital
Chiayi City, 61363
Taipei Veterans General Hospital
Taipei, 11217
About this study
Official title: A Pharmacokinetic and Pharmacodynamic Study of Glufast Tablets 10 mg (Mitiglinide) in Type 2 Diabetes Mellitus Patients With Normal or Moderate Impaired Hepatic Function
This clinical trial is designed to assess the effect of hepatic impairment on the pharmacokinetic and pharmacodynamic of glufast tablets 10 mg.
Read the detailed description
Mitiglinide calcium hydrate (Glufast Tablets) is an insulinotropic agent of the glinide class with rapid onset and is chemically designated as (+)-monocalcium bis[(2S,3a,7a-cis)-α-benzylhexahydro-γ-oxo-2-isoindolinebutyrate] dihydrate.By transiently increasing insulin secretion, mitiglinide exerts a hypoglycemic effect with rapid onset and short duration of action.This effect results from the inhibitory effect of mitiglinide on the ATP-sensitive potassium (KATP) channel current through binding to sulfonylurea receptor in pancreatic cells.
In an in vitro study, it was confirmed that mitiglinide is metabolized in liver and kidney, and the glucuronide and hydroxyl metabolites are mainly produced by drug metabolizing enzyme,UGT1A9 and 1A3, and by CYP2C9, respectively.Considering that the patient population with T2DM to be targeted appears to have hepatic impairment and the effects of liver dysfunction on pharmacokinetics and pharmacodynamics of mitiglinide are still unknown, this study was designed to investigate the pharmacokinetics (PK), pharmacodynamics (PD) and safety of mitiglinide when administered to T2DM patients with impaired hepatic function.
- Conditions
- Type 2 Diabetes Mellitus, Liver Dysfunction
- Being tested
- Mitiglinide
- Keywords
- Type 2 DM, mitiglinide, Pharmacokinetics, Pharmacodynamics, liver dysfunction
- Medical subject headings
- Diabetes Mellitus, Type 2, Liver Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MitiglinideDrug
Also called glufast
Day 1: one tablet of Mitiglinide 10mg with 240 ml of water approximately 5 mins before breakfast. An indwelling non-heparin catheter will be placed in an antecubital vein of the forearm or direct venipuncture will be adopted for blood sample collection at belowing time point:
For PK evaluation:
-30 (Predose), 5, 10, 15, 20, 30 min, 1.0, 1.5, 2.0, 3.0, 4.0, 5.0, 6.0, 7.0, 8.0, 9.0, 10 hr post dose (a total of 17 samples per subject)
For PD evaluation:
-30 (Predose), 15, 30 min, 1.0, 1.5, 2.0, 3.0, 4.0 hours post dose (a total of 8 samples per subject)
| Study group | Role | What they receive |
|---|---|---|
| T2DM with Child-Pugh A | Active comparator | All subjects with T2DM with normal hepatic function received a Mitiglinide Tablets 10 mg.
Intervention: Drug: Mitiglinide Tablets 10 mg Receives: Drug: Mitiglinide |
| T2DM with Child-Pugh B | Experimental | All subjects with T2DM with moderate impaired hepatic function received a MitiglinideTablets 10 mg.
Intervention:Drug: Mitiglinide Tablets 10 mg Receives: Drug: Mitiglinide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Peak concentration (Cmax)
Pharmacokinetic of mitiglinide
Measured: 1 day
Time to reach peak concentration (Tmax)
Pharmacokinetic of mitiglinide
Measured: 1day
Area under plasma concentration -time curve from time zero to time of last quantifiable concentration (AUC0-t)
Pharmacokinetic of mitiglinide
Measured: 1 day
Area under the plasma concentration-time curve from time zero to infinity of mitiglinide
Pharmacokinetic of mitiglinide
Measured: 1 day
The elimination rate constant
Pharmacokinetic of mitiglinide
Measured: 1 day
Volume of distribution (Vd/F)
Pharmacokinetic of mitiglinide
Measured: 1 day
Terminal elimination half-life (T1/2)
Pharmacokinetic of mitiglinide
Measured: 1 day
Total body clearance (CL/F)
Pharmacokinetic of mitiglinide
Measured: 1 day
Ratio of AUC0-t to AUC0-infinity
Pharmacokinetic of mitiglinide
Measured: 1 day
Area under the blood glucose concentration-time curve from time zero to time of last blood sample (AUC0-t,GLU)
Pharmacokinetic of mitiglinide
Measured: 1 day
Area under the blood glucose concentration(change from baseline)-time curve from time zero to time of last blood sample (ΔAUC0-t,GLU)
Pharmacokinetic of mitiglinide
Measured: 1 day
Blood glucose concentration change from baseline at 2 hours after drug administration
Pharmacokinetic of mitiglinide
Measured: 1 day
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Apr 2020
- Study start11 Feb 2014
- Primary completionApr 2018
- Study completionApr 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Type 2 Diabetes MellitusStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 16 participants (actual)
Sponsor and investigators
- Lead sponsor
- Orient Europharma Co., Ltd.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Yi-Hsiang Huang, Ph.D, Principal investigator, Taipei Veterans General Hospital, TaiwanWei-Ming Chen, MD, Principal investigator, Chang Gung Memorial Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04349696
- Sponsor's protocol ID
- OEP-P2012-01
- Status last verified
- Apr 2021
- First submitted
- 3 Mar 2020
- Last updated
- 30 Apr 2021
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 30 Apr 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pharmacokinetic and Pharmacodynamic Study of Glufast Tablets 10 mg (Mitiglinide) in Type 2 Diabetes Mellitus Patients With Normal or Moderate Impaired Hepatic Function
- ClinicalTrials.gov ID
- NCT04349696
- Acronym / sponsor ID
- OEP-P2012-01
- Conditions
- Type 2 Diabetes Mellitus, Liver Dysfunction
- Keywords
- Type 2 DM, mitiglinide, Pharmacokinetics, Pharmacodynamics, liver dysfunction
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 16 participants (actual)
- Lead sponsor
- Orient Europharma Co., Ltd.Industry (pharma, biotech, devices)
- Study start
- 11 Feb 2014 (actual)
- Primary completion
- Apr 2018 (actual)
- Study completion
- Apr 2018 (actual)
- First posted
- 16 Apr 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This clinical trial is designed to assess the effect of hepatic impairment on the pharmacokinetic and pharmacodynamic of glufast tablets 10 mg.
Detailed description
Mitiglinide calcium hydrate (Glufast Tablets) is an insulinotropic agent of the glinide class with rapid onset and is chemically designated as (+)-monocalcium bis[(2S,3a,7a-cis)-α-benzylhexahydro-γ-oxo-2-isoindolinebutyrate] dihydrate.By transiently increasing insulin secretion, mitiglinide exerts a hypoglycemic effect with rapid onset and short duration of action.This effect results from the inhibitory effect of mitiglinide on the ATP-sensitive potassium (KATP) channel current through binding to sulfonylurea receptor in pancreatic cells.
In an in vitro study, it was confirmed that mitiglinide is metabolized in liver and kidney, and the glucuronide and hydroxyl metabolites are mainly produced by drug metabolizing enzyme,UGT1A9 and 1A3, and by CYP2C9, respectively.Considering that the patient population with T2DM to be targeted appears to have hepatic impairment and the effects of liver dysfunction on pharmacokinetics and pharmacodynamics of mitiglinide are still unknown, this study was designed to investigate the pharmacokinetics (PK), pharmacodynamics (PD) and safety of mitiglinide when administered to T2DM patients with impaired hepatic function.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| T2DM with Child-Pugh A | Active comparator | Drug: MitiglinideAll subjects with T2DM with normal hepatic function received a Mitiglinide Tablets 10 mg. Intervention: Drug: Mitiglinide Tablets 10 mg |
| T2DM with Child-Pugh B | Experimental | Drug: MitiglinideAll subjects with T2DM with moderate impaired hepatic function received a MitiglinideTablets 10 mg. Intervention:Drug: Mitiglinide Tablets 10 mg |
Who may qualify
- Ages
- 20 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Subjects between 20-75 years of age, inclusive.
- Body mass index (BMI) values within 20-35 kg/m2.
- Diagnosed as type 2 diabetes mellitus and have fasting plasma glucose (FPG) less than 200 mg/dL at screen visit (for subjects under antidiabetic treatment).
- Having 2-hour postprandial glucose (PPG) level higher than or equal to 200 mg/dL at screen visit (for subjects who are antidiabetic treatment-naïve).
- Having fasting plasma glucose (FPG) higher than or equal to 126 mg/dL and less than 200 mg/dL at screen visit (for subjects who are antidiabetic treatment-naïve).
Key exclusion criteria (20 listed)
- Diagnosed as Type 1 (insulin-dependent) diabetes mellitus.
- Having 1-hour PPG or 2-hour PPG levels > 350 mg/dL at screen visit.
- History of diabetic ketoacidosis with or without coma.
- With unstable or rapidly progressive diabetic proliferative retinopathy or rapidly progressive diabetic neuropathy under investigator's judgment.
- Having clinically significant renal disease or dysfunction (e.g. serum creatinine >1.6 mg/dL) and concurrent anemia.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MitiglinideAlso: glufastDay 1: one tablet of Mitiglinide 10mg with 240 ml of water approximately 5 mins before breakfast. An indwelling non-heparin catheter will be placed in an antecubital vein of the forearm or direct venipuncture will be adopted for blood sample collection at belowing time point: For PK evaluation: -30 (Predose), 5, 10, 15, 20, 30 min, 1.0, 1.5, 2.0, 3.0, 4.0, 5.0, 6.0, 7.0, 8.0, 9.0, 10 hr post dose (a total of 17 samples per subject) For PD evaluation: -30 (Predose), 15, 30 min, 1.0, 1.5, 2.0, 3.0, 4.0 hours post dose (a total of 8 samples per subject) | Drug | T2DM with Child-Pugh A, T2DM with Child-Pugh B |
Primary outcome
Peak concentration (Cmax)
Time frame: 1 day
Pharmacokinetic of mitiglinide
Time to reach peak concentration (Tmax)
Time frame: 1day
Pharmacokinetic of mitiglinide
Area under plasma concentration -time curve from time zero to time of last quantifiable concentration (AUC0-t)
Time frame: 1 day
Pharmacokinetic of mitiglinide
Area under the plasma concentration-time curve from time zero to infinity of mitiglinide
Time frame: 1 day
Pharmacokinetic of mitiglinide
The elimination rate constant
Time frame: 1 day
Pharmacokinetic of mitiglinide
Volume of distribution (Vd/F)
Time frame: 1 day
Pharmacokinetic of mitiglinide
Terminal elimination half-life (T1/2)
Time frame: 1 day
Pharmacokinetic of mitiglinide
Total body clearance (CL/F)
Time frame: 1 day
Pharmacokinetic of mitiglinide
Ratio of AUC0-t to AUC0-infinity
Time frame: 1 day
Pharmacokinetic of mitiglinide
Area under the blood glucose concentration-time curve from time zero to time of last blood sample (AUC0-t,GLU)
Time frame: 1 day
Pharmacokinetic of mitiglinide
Area under the blood glucose concentration(change from baseline)-time curve from time zero to time of last blood sample (ΔAUC0-t,GLU)
Time frame: 1 day
Pharmacokinetic of mitiglinide
Blood glucose concentration change from baseline at 2 hours after drug administration
Time frame: 1 day
Pharmacokinetic of mitiglinide
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Apr 2021.
- Individual participant dataSharing planned: No
Related trials for Type 2 Diabetes Mellitus
Not yet recruitingPhase 3
Efficacy and Safety of Once-Weekly SHR-3167 Compared With Once-Daily Insulin Glargine in Adults With Insulin-Naive Type 2 Diabetes
Type 2 Diabetes
Active, not recruiting
Digital Reinforcement of Motivational Interviewing Micro-Skills Among Primary Care Healthcare Professionals
Hypertension (Without Type 2 Diabetes Mellitus)
Recruiting
Investigating Vascular Properties of HEMI and SPG Signals in Individuals With or at Risk for Chronic Kidney Disease
Chronic Kidney Disease, Hypertension (HTN)
Not yet recruitingPhase 3
A Study to Evaluate the Effectiveness and Safety of the Drug AZD6234 for Managing Weight in Adults Who Are Obese or Overweight. These Participants May or May Not Also Have Type 2 Diabetes
Obesity, Overweight
Not yet recruiting
Impact of Endoscopic Sleeve Gastroplasty (ESG) in Obese Adults With Type 2 Diabetes (T2D)
Type 2 Diabetes Mellitus (T2D), Obesity (BMI>30)
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Yi-Hsiang Huang, Ph.D principal investigator
Taipei Veterans General Hospital, Taiwan
Wei-Ming Chen, MD principal investigator
Chang Gung Memorial Hospital
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Mitiglinide in people with Type 2 Diabetes Mellitus and Liver Dysfunction, run by Orient Europharma Co., Ltd. at 2 sites in Taiwan.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 30 Apr 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Taiwan. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Peak concentration (Cmax) (time frame: 1 day). The study lists 12 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Apr 2021.