Clinical Trial to Evaluate Safety and pK Profile of Metformin Glycinate in Healthy Volunteers

Study Overview
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Brief Summary
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Metformin Glycinate is a novel biguanide compound developed as a potential candidate for the treatment of type 2 diabetes. Metformin Glycinate was found to improve metabolic control in naive patients with type 2 diabetes. The objective of this study is to evaluate the safety, tolerability and pK profile of Metformin Glycinate 620 mg QD, 1240 mg QD, 2480 mg QD, after administration of one single dose, in step A. In step A will be included 25 volunteers. In step B the objective is to evaluate Safety, tolerability and pK profile of Metformin Glycinate 620 mg BID, after administration of multiple dose during 8 days. In step B will be included 24 volunteers.

Official Title
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Randomized Clinical Trial to Evaluate Safety, Tolerability and PK-PD Profile of Metformin Glycinate 620 mg,1240 mg, 2480 mg and Metformin Chlorhydrate 1000 mg of One Single Dose, Multiple Dose and After Food Intake.

Conditions
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Healthy

Intervention / Treatment
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* Drug: Step A: metformin glycinate 620 mg single dose
* Drug: Step A: metformin glycinate 1240 mg single dose
* Drug: Step A: metformin glycinate 2480 mg single dose
* Drug: Step A: metformin hydrochloride 1000 mg single dose
* Drug: Step A: metformin glycinate 1240 mg,food intake
* Drug: Step B: metformin glycinate 620 mg BID
* Drug: Step B: metformin hydrochloride 500 mg BID


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age between 18 and 45 years. Weight within normal ranges (Quetelet index between 21 and 26) (weight (kg)/height (m2). Adequate physical examination and clinical history No organic and psychiatric disorder Normal Blood pressure, Pulse Rate, temperature and ECG. Lab test within normal values according to reference lab values of Biochemistry lab of Hospital Santa Creu I Sant Pau. It will be allowed changes according to clinical criteria of the clinical staff of ICIM-SANT PAU Females of childbearing potential with adequate contraceptive precautions, other than oral contraceptives and negative urine pregnancy test. No participation in any other clinical trial within the previous two months before the initiation of this study. No blood donation within the previous four weeks before the initiation of this study. Signed informed consent. Exclusion Criteria: Drugs or alcohol abuse. Consumer of stimulant drinks (> 5 coffees, teas, cola drinks). Smokers (> 10 cigars). Precedents of drugs allergy or hypersensitivity Intake of any other medication within the previous 15 days before this study. Positive HIV, HBV or HCV. Chronic disease (cardiovascular, respiratory, endocrine, gastrointestinal, hematologic, neurologic or others). Prior surgery within the previous six months before the initiation of this study. Pregnant women or breastfeeding or females of childbearing potential with no adequate contraceptive precautions, other than oral contraceptives.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Step A: metformin glycinate 620 mg<br>620mg single dose by mouth | Drug: Step A: metformin glycinate 620 mg single dose<br>* metformin glycinate 620 mg single dose<br>|
| Experimental: Step A: metformin glycinate 1240 mg<br>1240mg single dose by mouth | Drug: Step A: metformin glycinate 1240 mg single dose<br>* metformin glycinate 1240 mg single dose<br>|
| Experimental: Step A: metformin glycinate 2480 mg<br>2480mg single dose by mouth | Drug: Step A: metformin glycinate 2480 mg single dose<br>* metformin glycinate 2480 mg single dose<br>|
| Active Comparator: Step A: metformin hydrochloride 1000 mg<br>1000mg single dose by mouth | Drug: Step A: metformin hydrochloride 1000 mg single dose<br>* metformin Chlorhydrate 1000 mg single dose<br>|
| Experimental: Step A: metformin glycinate 1240 mg, food intake<br>1240mg single dose by mouth after food intake | Drug: Step A: metformin glycinate 1240 mg,food intake<br>* metformin glycinate 1240 mg, intake of food<br>|
| Experimental: Step B: metformin glycinate 620 mg BID<br>620mg BID for 8 days | Drug: Step B: metformin glycinate 620 mg BID<br>* metformin glycinate 620 mg BID, 8 days<br>|
| Active Comparator: Step B: metformin hydrochloride 500 mg BID<br>500mg tablets BID for 8 days | Drug: Step B: metformin hydrochloride 500 mg BID<br>* metformin Chlorhydrate 500 mg BID, 8 days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Step A: Number of Adverse Events of Metformin Glycinate 620 mg QD, 1240 mg QD, 2480 mg QD, after administration of one single dose | Tolerability: adverse events, systolic and diastolic blood pressure, pulse rate and temperature pulse rate and ECG alterations alterations in haematology, plasma chemistry, and urine analyses | 35 days | 
| Step B: Number of Adverse Events of Metformin Glycinate 620 mg BID, after administration of multiple dose during 8 days | Tolerability: adverse events, systolic and diastolic blood pressure, pulse rate and temperature pulse rate and ECG alterations alterations in haematology, plasma chemistry, and urine analyses | 25 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Step A: Bioavailability (AUC) of metformin glycinate 620 mg QD, 1240 mg QD, 2480 mg QD after administration of one single dose with metformin Chlorhydrate 1000 mg QD. |  | 36 hours | 
| Step A: Linear and dose-proportional (AUC) pharmacokinetic of 620 mg, 1240 mg and 2480 strengths of metformin glycinate |  | 36 hours | 
| Step A: Bioavailability (AUC) of metformin glycinate 1240 mg QD in fasted subjects and after the intake of fat rich breakfast |  | 36 hours | 
| Step A: Pharmacokinetic profile (AUC) of metformin glycinate 620mg QD, 1240 mg QD, 2480 mg QD after administration one single dose and pharmacokinetic profile of metformin chlorhydrate 1000mg QD. |  | 36 hours | 
| Step B: Bioavailability (AUC) of metformin glycinate 620 mg BID and bioavailability of metformin chlorhydrate 500mg BID, after administration of multiple doses during 8 days. |  | 8 days | 
| Step B: Pharmacokinetic profile (AUC) of metformin glycinate 620mg BID after administration of multiple doses during 8 days |  | 8 days | 
| Step A: Bioavailability (Cmax) of metformin glycinate 620 mg QD, 1240 mg QD, 2480 mg QD after administration of one single dose with metformin Chlorhydrate 1000 mg QD. |  | 36 hours | 
| Step A: Linear and dose-proportional pharmacokinetic (Cmax) of 620 mg, 1240 mg and 2480 strengths of metformin glycinate |  | 36 hours | 
| Step A: Bioavailability (Cmax) of metformin glycinate 1240 mg QD in fasted subjects and after the intake of fat rich breakfast |  | 36 hours | 
| Step A: Pharmacokinetic profile (Cmax) of metformin glycinate 620mg QD, 1240 mg QD, 2480 mg QD after administration one single dose and pharmacokinetic profile of metformin chlorhydrate 1000mg QD. |  | 36 hours | 
| Step B: Bioavailability (Cmax) of metformin glycinate 620 mg BID and bioavailability of metformin chlorhydrate 500mg BID, after administration of multiple doses during 8 days. |  | 8 days | 
| Step B: Pharmacokinetic profile (Cmax) of metformin glycinate 620mg BID after administration of multiple doses during 8 days |  | 8 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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metformin glycinate, pharmacokinetics, pharmacodynamics