A Study of the Effect of RG1662 on Metformin in Healthy Volunteers

Study Overview
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Brief Summary
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This single-center, non-randomized, open-label, two treatment, two period, fixed sequence crossover study will investigate the effect of RG1662 treatment on the activity of key renal transporters in healthy male and female participants using metformin. The effect of RG1662 on other renal function parameters will also be explored.

Conditions
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Healthy Volunteer

Intervention / Treatment
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* Other: Omnipaque 300
* Drug: RG1662
* Drug: metformin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy male or female participants, aged 18 to 60 years, inclusive A body mass index between 18 to 32 kg/m2, inclusive Informed consent and agreement to comply with study restrictions Exclusion Criteria: A history of epilepsy, convulsions or significant head injury Significant history of drug allergy or a known hypersensitivity to any of the ingredients of any of the study treatments Pregnant or lactating Impaired renal function or clinically relevant hematuria A history of lactic acidosis, or risk factors for lactic acidosis Any other clinically relevant abnormalities, concomitant diseases or ongoing medical conditions

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 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

Allocation: Non-Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: RG1662 plus metformin<br> | Other: Omnipaque 300<br>* 647 mg/mL of iohexol, equivalent to 300 mg/mL of iodine, used for assessment of glomerular function and other measure of renal function<br>Drug: RG1662<br>* Oral administration twice daily<br>Drug: metformin<br>* Single 850 mg dose of metformin<br>|
| Experimental: metformin alone<br> | Other: Omnipaque 300<br>* 647 mg/mL of iohexol, equivalent to 300 mg/mL of iodine, used for assessment of glomerular function and other measure of renal function<br>Drug: metformin<br>* Single 850 mg dose of metformin<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic parameters of metformin derived from plasma and urine concentrations of metformin: area under the concentration-time curve (AUC), maximum concentration (Cmax), renal clearance (CLr) [composite outcome measure] |  | Up to 9 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic parameters derived from plasma concentrations of RG1662: AUC, Cmax, time to maximum concentration (Tmax), and minimum concentration (Ctrough)[composite outcome measure] |  | Up to 9 weeks | 
| Pharmacodynamics: renal function measured by derivation of glomerular filtration rate (GFR) from plasma concentrations of iohexol. |  | Up to 9 weeks | 
| Incidence of adverse events (AEs) |  | Up to 9 weeks |