A Pharmacokinetic and Pharmacodynamic Study of Metformin and Canagliflozin in Healthy Adult Volunteers

Study Overview
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Brief Summary
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The purpose of the study is to investigate the potential interaction between multiple oral doses of canagliflozin and a single oral dose of metformin in healthy adult volunteers.

Detailed Description
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This is an open-label (volunteers will know the names of treatments they are assigned) single-center study of canagliflozin and metformin in healthy adult volunteers. Canagliflozin (a Sodium-Glucose Cotransporter 2 inhibitor) is currently under development to lower blood sugar levels in patients with type 2 diabetes mellitus (T2DM) and metformin is an approved treatment for patients with T2DM. Canagliflozin will be administered orally (by mouth) as a single 300-mg tablet on Days 4, 5, 6, 7, and 8 and metformin will be administered orally as two 1,000 mg tablets on Days 1 and 8. Both canagliflozin and metformin tablets will be taken with 8 ounces (240 mL) of water.

Official Title
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An Open-Label, Fixed Sequence Study to Investigate the Potential for Pharmacokinetic and Pharmacodynamic Interaction Between Single-Dose Metformin and Multiple-Dose Canagliflozin in Healthy Subjects

Conditions
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Healthy

Intervention / Treatment
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* Drug: Canagliflozin/Metformin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy volunteers with a body mass index (BMI, a measure of a person's weight in relation to height) between 18 and 30 kg/m2, inclusive. Exclusion Criteria: History of or current clinically significant medical illness as determined by the Investigator History of clinically significant allergies, especially known hypersensitivity or intolerance to lactose Known allergy to canagliflozin or metformin or any of the excipients of the formulation of canagliflozin or metformin Known allergy to heparin or history of heparin induced thrombocytopenia.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 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: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 001<br>Canagliflozin/Metformin Two 1000-mg tablets of metformin on Day 1 followed by one 300-mg tablet of canagliflozin once daily on Days 4 through 8 followed by two 1000-mg tablets of metformin and one 300-mg tablet of canagliflozin on Day 8. | Drug: Canagliflozin/Metformin<br>* Two 1000-mg tablets of metformin on Day 1 followed by one 300-mg tablet of canagliflozin once daily on Days 4 through 8, followed by two 1000-mg tablets of metformin and one 300-mg tablet of canagliflozin on Day 8.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma concentrations of canagliflozin |  | At protocol-specified times up to Day 11 | 
| Plasma concentrations of metformin |  | At protocol-specified times up to Day 11) | 
| Urine concentrations of metformin |  | At protocol-specified times up to Day 10) | 
| Plasma concentrations of glucose |  | Up to Day 9 | 
| Urinary glucose excretion (UGE) |  | Up to Day 11 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The number and type of adverse events reported |  | Up to Day 8 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Canagliflozin, Metformin (GLUCOPHAGE IR), Pharmacokinetics, Pharmacodynamics