The relationship between genetic polymorphisms in the organic cation transporter genes and the pharmacokinetics and pharmacodynamics of metformin - The genetics of metformin excretio

Phase 1

• Conditions: Type 2 diabetes mellitus

• Registration Number: EUCTR2005-000619-85-GB
• Lead Sponsor: The University of Liverpool

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2005-05-04
• Last Update Posted: 27 July 2020

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 200

Inclusion Criteria

1. Subject is aged between 25 and 85 years of age inclusive.
2. Subject has given signed informed consent (written and witnessed).
3. Subject has a diagnosis of type 2 diabetes mellitus, regardless of how and when that diagnosis was established.
4. Subject’s anti-hyperglycaemic medication consists of metformin monotherapy, at a dosage of 500mg three times daily and that dosage has been established for a period of at least 3 months.
5. Subject has not missed any metformin doses for a period of at least 5 days and compliance has been assessed through a validated compliance questionnaire.
6. Subject is able to recall at least approximate timing of dosing (within 30 minutes).
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1. Subject is, in the opinion of the Investigator, not suitable to participate in the study.
2. Subject has a diagnosis of pernicious anaemia.
3. Subject is also prescribed additional anti-hyperglycaemic medication such as sulphonylureas, meglitinide analogues, thiazolidinediones or insulin.
4. Subject has taken any known inhibitor of OCT1 or OCT2, such as amantadine, cimetidine, clonidine, desipramine, midazolam, procainamide, quinidine, quinine, or verapamil in the last 4 weeks.
5. Subject has participated in strenuous physical activity, defined as more than typical walking pace, for a period of 8 hours prior to study entry.
6. Subject has an alcohol intake greater than the recommended weekly safe drinking limits (>21 units in men; >14 units in women).

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To characterise the relationship between plasma metformin pharmacokinetics and the presence of polymorphisms in human organic cation transporter genes in patients with type 2 diabetes mellitus on chronic metformin therapy.;Secondary Objective: To characterise the relationship between the plasma pharmacokinetics and the levels of vitamin B12 and lactate in patients with type 2 diabetes mellitus on chronic metformin therapy.;Primary end point(s): 1. OCT1 and OCT2 genotype<br>Identification of the following SNPs will be undertaken:<br>a) OCT1-M408V<br>b) OCT1-M420del<br>c) OCT1-R61C<br>d) OCT2-A270S<br>2. Metformin pharmacokinetic (PK) parameters:<br>a) Plasma metformin concentration (co-primary outcome measure)<br>b) Predicted metformin clearance (co-primary outcome measure)<br>c) Predicted metformin AUC (area under the plasma concentration-time curve)<br>d) Predicted metformin Cmax<br>