Clinical Trial to Evaluate Safety and pK Profile of Metformin Glycinate in Healthy Volunteers (NTC00940472)

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.

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.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: 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

• Study Type: Interventional
• Enrollment (Actual): 49
• Phase: Phase 1

Contacts and Locations

Study Locations

• Spain
  • Barcelona, Spain, 08025
    • Centre d'Investigació de Medicaments Hospital de la Santa Creu i Sant Pau

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

7

Arms and Interventions

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

What is the study measuring?

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	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

Collaborators and Investigators

• Sponsor: Laboratorios Silanes S.A. de C.V.
• Investigators: Study Chair: Rosa M Antonijoan, MD, Centre d'Investigació de Medicaments Hospital de la Santa Creu i Sant Pau

Study record dates

Study Major Dates

• Study Start: December 1, 2011
• Primary Completion (Actual): March 1, 2012
• Study Completion (Actual): March 1, 2013

Study Registration Dates

• First Submitted: February 9, 2012
• First Submitted That Met QC Criteria: March 20, 2012
• First Posted (Estimate): March 22, 2012

Study Record Updates

• Last Update Posted (Actual): January 30, 2018
• Last Update Submitted That Met QC Criteria: January 26, 2018
• Last Verified: January 1, 2018

More Information

Terms related to this study

• Keywords: pharmacokinetics; metformin glycinate; pharmacodynamics
• Additional Relevant MeSH Terms: Hypoglycemic Agents; Physiological Effects of Drugs; Metformin
• Other Study ID Numbers: NTC00940472