Pharmacogenetics of SGLT2 Inhibitors | NCT02462421

ID	Type	Description	Link
R21DK105401	U.S. NIH Grant/Contract		View source

Pharmacogenetics of SGLT2 Inhibitors | NCT02462421 | Trialant

Sponsor/Collaborators Module

Name	Class
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)	NIH

Description Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Wild type genotype	Active Comparator	Research subjects with wild type genotypes at three candidate genes encoding sodium-dependent glucose transporter-3, sodium-dependent glucose transporter-4, and glucose transporter-9 (abbreviated as SLC5A4, SLC5A9, SLC2A9, respectively) will be studied before and after canagliflozin treatment.	Drug: Canagliflozin
Nonsense mutation in SLC5A4	Experimental	Research subjects who are homozygous for nonsense mutation in SLC5A4 (sodium-dependent glucose transporter-3) will be studied before and after canagliflozin treatment.	Drug: Canagliflozin
Nonsense mutation in SLC5A9	Experimental	Research subjects who are homozygous for nonsense mutation in SLC5A9 (sodium-dependent glucose transporter-4) will be studied before and after canagliflozin treatment.	Drug: Canagliflozin
Missense variant in SLC2A9	Experimental	Research subjects who are homozygous for nonsynonymous variant in glucose transporter-9 (SLC2A9) will be studied before and after canagliflozin treatment.	Drug: Canagliflozin

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Canagliflozin	Drug	A single dose of canagliflozin (300 mg, p.o.) will be administered prior to assessing pharmacodynamic response.	Missense variant in SLC2A9 Nonsense mutation in SLC5A4

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Urinary Excretion of Glucose (Measured During the 24 Hours Following Administration of Canagliflozin)	The pharmacodynamic response to canagliflozin will be assessed by measuring the increase in 24 hour urinary glucose excretion.	24 hours after administration of canagliflozin
Change in Fractional Excretion of Uric Acid (the Difference Between Data After Administration of Canagliflozin Minus Data Before Administration of Canagliflozin)	For the study arm focused on individuals with a genetic variant in SLC2A9, the pharmacodynamic response to canagliflozin will be assessed by measuring the absolute change in fractional excretion of uric acid in the urine. Fractional excretion of uric acid represents the fraction of the calculated filtered uric acid load (serum uric acid level multiplied by the measured creatinine clearance rate) that was excreted in the urine.	24 hour urine collection after administration of canagliflozin

Secondary Outcomes

Measure	Description	Time Frame
Canagliflozin-induced Change in Urinary Excretion of Sodium	The pharmacodynamic response to canagliflozin will be assessed by measuring the % increase in 24 hour urinary excretion of sodium.	24 hours after administration of canagliflozin
Canagliflozin-induced Change in Serum Creatinine

Name	Affiliation	Role
Simeon I Taylor, MD, PhD	University of Maryland, Baltimore	Study Chair

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
36993363	Derived	Taylor SI, Montasser ME, Yuen AH, Fan H, Yazdi ZS, Whitlatch HB, Mitchell BD, Shuldiner AR, Muniyappa R, Streeten EA, Beitelshees AL. Acute pharmacodynamic responses to exenatide: Drug-induced increases in insulin secretion and glucose effectiveness. medRxiv [Preprint]. 2023 May 3:2023.03.15.23287166. doi: 10.1101/2023.03.15.23287166.
36945579	Derived	Taylor SI, Cherng HR, Yazdi ZS, Montasser ME, Whitlatch HB, Mitchell BD, Shuldiner AR, Streeten EA, Beitelshees AL. Pharmacogenetics of SGLT2 Inhibitors: Validation of a sex-agnostic pharmacodynamic biomarker. medRxiv [Preprint]. 2023 Jun 12:2023.03.07.23286875. doi: 10.1101/2023.03.07.23286875.

Arm/Group Information

ID	Title	Description
FG000	Wild Type Genotype	Research subjects with wild type genotypes at three candidate genes encoding sodium-dependent glucose transporter-3, sodium-dependent glucose transporter-4, and glucose transporter-9 (abbreviated as SLC5A4, SLC5A9, SLC2A9, respectively) will be studied before and after canagliflozin treatment. Canagliflozin: A single dose of canagliflozin (300 mg, p.o.) will be administered prior to assessing pharmacodynamic response.
FG001	Nonsense Mutation in SLC5A4	Research subjects who are homozygous for nonsense mutation in SLC5A4 (sodium-dependent glucose transporter-3) will be studied before and after canagliflozin treatment. Canagliflozin: A single dose of canagliflozin (300 mg, p.o.) will be administered prior to assessing pharmacodynamic response.
FG002	Nonsense Mutation in SLC5A9	Research subjects who are homozygous for nonsense mutation in SLC5A9 (sodium-dependent glucose transporter-4) will be studied before and after canagliflozin treatment. Canagliflozin: A single dose of canagliflozin (300 mg, p.o.) will be administered prior to assessing pharmacodynamic response.
FG003	Missense Variant in SLC2A9	Research subjects who are homozygous for nonsynonymous variant in glucose transporter-9 (SLC2A9) will be studied before and after canagliflozin treatment. Canagliflozin: A single dose of canagliflozin (300 mg, p.o.) will be administered prior to assessing pharmacodynamic response.

Periods

Title

Milestones

Reasons Not Completed

Overall Study

Type	Comment	Milestone Data
STARTED		FG00013 subjects FG0014 subjects FG0026 subjects FG0037 subjects
COMPLETED		FG00013 subjects FG0014 subjects FG0026 subjects FG0037 subjects
NOT COMPLETED		FG0000 subjects FG0010 subjects FG0020 subjects FG0030 subjects

Baseline Characteristics Module

Arm/Group Information

ID	Title	Description
BG000	Wild Type Genotype	Research subjects with wild type genotypes at three candidate genes encoding sodium-dependent glucose transporter-3, sodium-dependent glucose transporter-4, and glucose transporter-9 (abbreviated as SLC5A4, SLC5A9, SLC2A9, respectively) will be studied before and after canagliflozin treatment. Canagliflozin: A single dose of canagliflozin (300 mg, p.o.) will be administered prior to assessing pharmacodynamic response.

Units	Counts
Participants	BG000

Title	Description	Population Description	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Denominator Units Selected	Denominators	Classes
Age, Continuous			Mean

Outcome Measures Module

Outcome Measures

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Urinary Excretion of Glucose (Measured During the 24 Hours Following Administration of Canagliflozin)

The pharmacodynamic response to canagliflozin will be assessed by measuring the increase in 24 hour urinary glucose excretion.

The entire population of 30 research participants comprised the database for this analysis.

Posted

Mean

Standard Error

glucose (g)/creatinine (g)

24 hours after administration of canagliflozin

ID	Title	Description
OG000	Wild Type Genotype	Research subjects with wild type genotypes at three candidate genes encoding sodium-dependent glucose transporter-3, sodium-dependent glucose transporter-4, and glucose transporter-9 (abbreviated as SLC5A4, SLC5A9, SLC2A9, respectively) will be studied before and after canagliflozin treatment. Canagliflozin: A single dose of canagliflozin (300 mg, p.o.) will be administered prior to assessing pharmacodynamic response.

Adverse Events Module

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Total Population of Participants in the Clinical Trial	All individuals received the same intervention. With such a small trial and so few adverse events, it is not meaningful to report adverse events for each arm separately. Adverse events were not collected or analyzed according to genotype status.

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Accident while driving a horse-drawn buggy	Musculoskeletal and connective tissue disorders		Non-systematic Assessment	At a time when the participant was not taking the study drug (canagliflozin), the patient was driving a horse-drawn buggy and she experienced an accident without any significant injury.

More Info Module

Certain Agreements

Title	Organization	Phone	Extension	Email
Dr. Simeon Taylor (Professor of Medicine)	University of Maryland School of Medicine	410-706-6439		staylor2@som.umaryland.edu

Uploaded Document Information

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot_SAP	Yes	Yes	No	Study Protocol and Statistical Analysis Plan	May 16, 2022	May 16, 2022	Prot_SAP_000.pdf

Condition Browse Module

ID	Term
D003920	Diabetes Mellitus
D006073	Gout
D033461	Hyperuricemia

ID	Term
D044882	Glucose Metabolism Disorders
D008659	Metabolic Diseases
D009750	Nutritional and Metabolic Diseases
D004700	Endocrine System Diseases

Intervention Browse Module

ID	Term
D000068896	Canagliflozin

ID	Term
D013876	Thiophenes
D013457	Sulfur Compounds
D009930	Organic Chemicals
D006573	Heterocyclic Compounds, 1-Ring

Ethnicity (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Hispanic or Latino	BG0000 BG0010 BG0020 BG0030 BG0040
Not Hispanic or Latino	BG00013 BG0014 BG0026 BG0037 BG004
Unknown or Not Reported	BG0000 BG0010 BG0020 BG0030 BG004

Race (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
American Indian or Alaska Native	BG0000 BG0010 BG0020 BG0030 BG0040
Asian	BG0000 BG0010 BG0020 BG0030 BG004
Native Hawaiian or Other Pacific Islander	BG0000 BG0010 BG0020 BG0030 BG004
Black or African American	BG0000 BG0010 BG0020 BG0030 BG004
White	BG00013 BG0014 BG0026 BG0037 BG004
More than one race	BG0000 BG0010 BG0020 BG0030 BG004
Unknown or Not Reported	BG0000 BG0010 BG0020 BG0030 BG004

Fractional excretion of uric acid

Mean

Standard Deviation

% of filtered uric acid that is excreted

Title

Denominators

Categories

Title	Measurements
	BG0008.0± 1.3 BG0019.4± 3.7 BG0026.2± 1.5 BG0039.8± 2.9 BG0048.5± 2.4

Group IDs	Group Description	Statistical Method	P-Value	P-Value Comment	Non-Inferiority Type	Non-Inferiority Comment
OG000 OG001	Each of the variant genotypes was compared to the control group (homozygous for major alleles at all three genetic loci) in an unpaired t-test. The study was terminated early because it was clear that we would not meet our recruitment targets and that the study was likely underpowered. Null hypothesis: pharmacodynamic response is the same in the control group and homozygotes for the genetic variant.	t-test, 2 sided	0.92	No adjustment for multiple comparisons. Viewed as unnecessary inasmuch as none of the comparisons achieved p<0.05.	Other	Probability that the observed difference was the result of random variation rather than a difference between the two populations.
OG000 OG002	Null hypothesis: pharmacodynamic response is the same in the control group and homozygotes for the genetic variant.	t-test, 2 sided	0.63	Not corrected for multiple comparisons	Other	Probability that the observed difference was the result of random variation rather than a difference between the two populations.
OG000 OG003	Null hypothesis: pharmacodynamic response is the same in the control group and homozygotes for the genetic variant.	t-test, 2 sided	0.86	Not adjusted for multiple comparisons	Other	Probability that the observed difference was the result of random variation rather than a difference between the two populations.

Primary

Change in Fractional Excretion of Uric Acid (the Difference Between Data After Administration of Canagliflozin Minus Data Before Administration of Canagliflozin)

For the study arm focused on individuals with a genetic variant in SLC2A9, the pharmacodynamic response to canagliflozin will be assessed by measuring the absolute change in fractional excretion of uric acid in the urine. Fractional excretion of uric acid represents the fraction of the calculated filtered uric acid load (serum uric acid level multiplied by the measured creatinine clearance rate) that was excreted in the urine.

Data from all 30 patients are summarized. The primary statistical analysis is based on comparison of the 13 "wild type" genotype versus the 7 patients who are homozygous for the variant in SLC2A9 (GLUT9).

Posted

Mean

Standard Error

absolute change in fractional excretion

24 hour urine collection after administration of canagliflozin

ID	Title	Description
OG000	Wild Type Genotype	Research subjects with wild type genotypes at three candidate genes encoding sodium-dependent glucose transporter-3, sodium-dependent glucose transporter-4, and glucose transporter-9 (abbreviated as SLC5A4, SLC5A9, SLC2A9, respectively) will be studied before and after canagliflozin treatment. Canagliflozin: A single dose of canagliflozin (300 mg, p.o.) will be administered prior to assessing pharmacodynamic response.
OG001	Nonsense Mutation in SLC5A4	Research subjects who are homozygous for nonsense mutation in SLC5A4 (sodium-dependent glucose transporter-3) will be studied before and after canagliflozin treatment. Canagliflozin: A single dose of canagliflozin (300 mg, p.o.) will be administered prior to assessing pharmacodynamic response.
OG002	Nonsense Mutation in SLC5A9	Research subjects who are homozygous for nonsense mutation in SLC5A9 (sodium-dependent glucose transporter-4) will be studied before and after canagliflozin treatment. Canagliflozin: A single dose of canagliflozin (300 mg, p.o.) will be administered prior to assessing pharmacodynamic response.
OG003	Missense Variant in SLC2A9	Research subjects who are homozygous for nonsynonymous variant in glucose transporter-9 (SLC2A9) will be studied before and after canagliflozin treatment. Canagliflozin: A single dose of canagliflozin (300 mg, p.o.) will be administered prior to assessing pharmacodynamic response.
OG004	Total Population	Aggregate of all research participants in the four genotypes comprising the four arms of the study.

Units	Counts
Participants	OG00013 OG0014 OG0026 OG003

Title

Denominators

Categories

Title	Measurements
	OG0000.25± 0.02 OG0010.25± 0.02 OG0020.28± 0.04 OG003

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG003	The study was terminated early because of slow recruitment. As a result the study did not achieve the statistical power that had been planned.	t-test, 2 sided		0.04	Because the study was terminated early, we did not have sufficient statistical power to adjust for multiple comparisons. We are reporting a nominal p-value without adjusting for multiple comparisons													Other	We compared the two groups ("wild type" versus SLC2A9 variant homozygotes. Null hypothesis: there are no differences between the two groups with respect to the pharmacodynamic effect of canagliflozin on fractional excretion of uric acid in the urine.

Secondary

Canagliflozin-induced Change in Urinary Excretion of Sodium

The pharmacodynamic response to canagliflozin will be assessed by measuring the % increase in 24 hour urinary excretion of sodium.

Posted

Mean

Standard Error

% increase in urinary Na excretion

24 hours after administration of canagliflozin

ID	Title	Description
OG000	Wild Type Genotype	Research subjects with wild type genotypes at three candidate genes encoding sodium-dependent glucose transporter-3, sodium-dependent glucose transporter-4, and glucose transporter-9 (abbreviated as SLC5A4, SLC5A9, SLC2A9, respectively) will be studied before and after canagliflozin treatment. Canagliflozin: A single dose of canagliflozin (300 mg, p.o.) will be administered prior to assessing pharmacodynamic response.
OG001	Nonsense Mutation in SLC5A4	Research subjects who are homozygous for nonsense mutation in SLC5A4 (sodium-dependent glucose transporter-3) will be studied before and after canagliflozin treatment. Canagliflozin: A single dose of canagliflozin (300 mg, p.o.) will be administered prior to assessing pharmacodynamic response.
OG002	Nonsense Mutation in SLC5A9	Research subjects who are homozygous for nonsense mutation in SLC5A9 (sodium-dependent glucose transporter-4) will be studied before and after canagliflozin treatment. Canagliflozin: A single dose of canagliflozin (300 mg, p.o.) will be administered prior to assessing pharmacodynamic response.
OG003	Missense Variant in SLC2A9	Research subjects who are homozygous for nonsynonymous variant in glucose transporter-9 (SLC2A9) will be studied before and after canagliflozin treatment. Canagliflozin: A single dose of canagliflozin (300 mg, p.o.) will be administered prior to assessing pharmacodynamic response.
OG004	Total Population	Aggregate of all participants in the five study arms

Units	Counts
Participants	OG00013 OG0014 OG0026 OG003

Title

Denominators

Categories

Title	Measurements
	OG00020± 12 OG00166± 17 OG00218± 10 OG003

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	Null hypothesis: pharmacodynamic response is the same in the control group and homozygotes for the genetic variant.	t-test, 2 sided		0.07	Not corrected for multiple comparisons													Other	Probability that the observed difference was the result of random variation rather than a difference between the two populations.

Secondary

Canagliflozin-induced Change in Serum Creatinine

The pharmacodynamic response to canagliflozin will be assessed by measuring changes in serum creatinine

Posted

Mean

Standard Error

mg/dL

24 hours after administration of canagliflozin

ID	Title	Description
OG000	Wild Type Genotype	Research subjects with wild type genotypes at three candidate genes encoding sodium-dependent glucose transporter-3, sodium-dependent glucose transporter-4, and glucose transporter-9 (abbreviated as SLC5A4, SLC5A9, SLC2A9, respectively) will be studied before and after canagliflozin treatment. Canagliflozin: A single dose of canagliflozin (300 mg, p.o.) will be administered prior to assessing pharmacodynamic response.
OG001	Nonsense Mutation in SLC5A4	Research subjects who are homozygous for nonsense mutation in SLC5A4 (sodium-dependent glucose transporter-3) will be studied before and after canagliflozin treatment. Canagliflozin: A single dose of canagliflozin (300 mg, p.o.) will be administered prior to assessing pharmacodynamic response.
OG002	Nonsense Mutation in SLC5A9	Research subjects who are homozygous for nonsense mutation in SLC5A9 (sodium-dependent glucose transporter-4) will be studied before and after canagliflozin treatment. Canagliflozin: A single dose of canagliflozin (300 mg, p.o.) will be administered prior to assessing pharmacodynamic response.
OG003	Missense Variant in SLC2A9	Research subjects who are homozygous for nonsynonymous variant in glucose transporter-9 (SLC2A9) will be studied before and after canagliflozin treatment. Canagliflozin: A single dose of canagliflozin (300 mg, p.o.) will be administered prior to assessing pharmacodynamic response.
OG004	Total Population	Aggregate of all participants in the five study arms

Units	Counts
Participants	OG00013 OG0014 OG0026 OG003

Title

Denominators

Categories

Title	Measurements
	OG0000.06± 0.02 OG001-0.03± 0.02 OG0020.07± 0.02 OG003

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	Null hypothesis: pharmacodynamic response is the same in the control group and homozygotes for the genetic variant.	t-test, 2 sided		<0.01	Not corrected for multiple comparisons.													Other	Probability that the observed difference was the result of random variation rather than a difference between the two populations.

Secondary

Canagliflozin-induced Change in Serum Uric Acid

The pharmacodynamic response to canagliflozin will be assessed by measuring changes in serum uric acid level

Data from all 30 research participants will be summarized. Statistical analysis will focus on comparisons between the 13 participants who are homozygous for the major alleles at all three loci versus the three groups who are homozygous for each of the three other genetic variants.

Posted

Mean

Standard Error

% change in serum uric acid level

24 hours after administration of canagliflozin

ID	Title	Description
OG000	Wild Type Genotype	Research subjects with wild type genotypes at three candidate genes encoding sodium-dependent glucose transporter-3, sodium-dependent glucose transporter-4, and glucose transporter-9 (abbreviated as SLC5A4, SLC5A9, SLC2A9, respectively) will be studied before and after canagliflozin treatment. Canagliflozin: A single dose of canagliflozin (300 mg, p.o.) will be administered prior to assessing pharmacodynamic response.
OG001	Nonsense Mutation in SLC5A4	Research subjects who are homozygous for nonsense mutation in SLC5A4 (sodium-dependent glucose transporter-3) will be studied before and after canagliflozin treatment. Canagliflozin: A single dose of canagliflozin (300 mg, p.o.) will be administered prior to assessing pharmacodynamic response.
OG002	Nonsense Mutation in SLC5A9	Research subjects who are homozygous for nonsense mutation in SLC5A9 (sodium-dependent glucose transporter-4) will be studied before and after canagliflozin treatment. Canagliflozin: A single dose of canagliflozin (300 mg, p.o.) will be administered prior to assessing pharmacodynamic response.
OG003	Missense Variant in SLC2A9	Research subjects who are homozygous for nonsynonymous variant in glucose transporter-9 (SLC2A9) will be studied before and after canagliflozin treatment. Canagliflozin: A single dose of canagliflozin (300 mg, p.o.) will be administered prior to assessing pharmacodynamic response.
OG004	Total Study Population	Aggregate of research participants in all four arms of the study

Units	Counts
Participants	OG00013 OG0014 OG0026 OG003

Title

Denominators

Categories

Title	Measurements
	OG000-22± 1.9 OG001-29± 4.2 OG002-12± 2.6 OG003

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	The "wild type" genotype group was compared to homozygotes for each of the three other genotypes.	t-test, 2 sided		0.20	Because the study was terminated early, the study does not have sufficient statistical power to adjust for multiple comparisons. Accordingly, nominal p-values are reported.													Other	Null hypothesis: None of the three genotypes is associated with an alteration in the pharmacodynamic effect of canagliflozin on urinary Na excretion

Secondary

Canagliflozin-induced Change in Fasting Plasma Glucose

The magnitude of the change in fasting plasma glucose 24 hours after administration of canagliflozin (300 mg)

Posted

Mean

Standard Error

mg/dL

24 hrs

ID	Title	Description
OG000	Wild Type Genotype	Research subjects with wild type genotypes at three candidate genes encoding sodium-dependent glucose transporter-3, sodium-dependent glucose transporter-4, and glucose transporter-9 (abbreviated as SLC5A4, SLC5A9, SLC2A9, respectively) will be studied before and after canagliflozin treatment. Canagliflozin: A single dose of canagliflozin (300 mg, p.o.) will be administered prior to assessing pharmacodynamic response.
OG001	Nonsense Mutation in SLC5A4	Research subjects who are homozygous for nonsense mutation in SLC5A4 (sodium-dependent glucose transporter-3) will be studied before and after canagliflozin treatment. Canagliflozin: A single dose of canagliflozin (300 mg, p.o.) will be administered prior to assessing pharmacodynamic response.
OG002	Nonsense Mutation in SLC5A9	Research subjects who are homozygous for nonsense mutation in SLC5A9 (sodium-dependent glucose transporter-4) will be studied before and after canagliflozin treatment. Canagliflozin: A single dose of canagliflozin (300 mg, p.o.) will be administered prior to assessing pharmacodynamic response.
OG003	Missense Variant in SLC2A9	Research subjects who are homozygous for nonsynonymous variant in glucose transporter-9 (SLC2A9) will be studied before and after canagliflozin treatment. Canagliflozin: A single dose of canagliflozin (300 mg, p.o.) will be administered prior to assessing pharmacodynamic response.
OG004	Total Study Population	Aggregate of research participants in all four arms of the study

Units	Counts
Participants	OG00013 OG0014 OG0026 OG003

Title

Denominators

Categories

Title	Measurements
	OG000-5.0± 1.5 OG001-2.0± 1.6 OG002-4.7± 2.8 OG003

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	Null hypothesis: pharmacodynamic response is the same in the control group and homozygotes for the genetic variant.	t-test, 2 sided		0.21	Not corrected for multiple comparisons.													Other	Probability that the observed difference was the result of random variation rather than a difference between the two populations.