Genetics of Response to Canagliflozin

Pharmacogenomics to Predict Responses to SGLT2 Inhibitors

Sponsors

Lead Sponsor: University of Maryland, Baltimore

Collaborator: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Source University of Maryland, Baltimore
Brief Summary

Five daily doses of canagliflozin (300 mg) will be administered to healthy volunteers. Pharmacodynamic responses to canagliflozin will be assessed both at 2 days and 6 days after administration of the first dose of canagliflozin. A genome-wide association study (GWAS) will be conducted to search for genetic variants that are associated with each of the pharmacodynamic responses to canagliflozin.

Detailed Description

After obtaining informed consent, healthy Amish research subjects will be screened for eligibility. Immediately after obtaining blood samples for baseline clinical chemistry tests wills, patients will initiate 5 days of canagliflozin (300 mg) treatment. Fasting blood samples will be obtained to assess pharmacodynamic responses at both 48 hours and 120 hours after initiating canagliflozin. The principal pharmacodynamic responses will include 24 hour urinary excretion of glucose, serum chemistries (phosphorus, FGF23, 1,25-dihydroxyvitamin D, parathyroid hormone (PTH), glucagon, beta-hydroxybutyrate, acetoacetate, procollagen type I N-terminal peptide (P1NP), and beta-CTX). Research subjects will undergo genotyping, and a genome-wide association study will be conducted to search for genetic variants that are associated with pharmacodynamic responses to canagliflozin.

Overall Status Enrolling by invitation
Start Date September 2016
Completion Date June 30, 2024
Primary Completion Date June 30, 2023
Phase Phase 1
Study Type Interventional
Primary Outcome
Measure Time Frame
Urinary glucose excretion (during the time interval 24-48 hours after first administration of canagliflozin) 24-48 hours
Secondary Outcome
Measure Time Frame
Bone-related biomarkers 48 hrs
Bone-related biomarkers 120 hrs
Ketosis-related biomarkers 48 hrs
Ketosis-related biomarkers 120 hurs
Serum uric acid 48 hrs
Serum uric acid 120 hrs
Enrollment 700
Condition
Intervention

Intervention Type: Drug

Intervention Name: Canagliflozin

Description: Healthy volunteers will receive canagliflozin (300 mg per day) in the morning for five days.

Arm Group Label: Single arm

Other Name: Invokana (brand name for canagliflozin)

Eligibility

Criteria:

Inclusion Criteria:

- Of Amish descent

- Age 18 or older

- BMI: 18-40 kg/m2

Exclusion Criteria:

- Known allergy to canagliflozin

- History of diabetes, random glucose greater than 200 mg/dL, or HbA1c greater than or equal to 6.5%

- Currently taking diuretics, antihypertensive medication uric acid lowering medications, or other medication that the investigator judges will make interpretation of the results difficult

- Significant debilitating chronic cardiac, hepatic, pulmonary, or renal disease or other diseases that the investigator judges will make interpretation of the results difficult or increase the risk of participation

- Seizure disorder

- Unwilling to go off of vitamin supplements and over the counter medication (except for acetaminophen) for at least two weeks prior to the first home visit and agree to avoid these medications for the duration of the study.

- Positive urine human chorionic gonadotropin test or known pregnancy within 3 months of the start of the study

- Estimated glomerular filtration rate less than 60 mL/min

- Currently breast feeding or breast feeding within 3 month of the start of the study

- Liver function tests greater than 2 times the upper limit of normal

- Hematocrit less than 35%

- Abnormal thyroid hormone stimulating hormone

Gender: All

Minimum Age: 18 Years

Maximum Age: N/A

Healthy Volunteers: Accepts Healthy Volunteers

Overall Official
Last Name Role Affiliation
Simeon I Taylor, MD, PhD Principal Investigator Unversity of Maryland School of Medicine
Verification Date

August 2019

Responsible Party

Type: Principal Investigator

Investigator Affiliation: University of Maryland, Baltimore

Investigator Full Name: Simeon I. Taylor

Investigator Title: Professor of Medicine

Keywords
Has Expanded Access No
Condition Browse
Number Of Arms 1
Arm Group

Label: Single arm

Type: Experimental

Description: Healthy volunteers will receive canagliflozin to assess pharmacodynamic responses to drug.

Patient Data No
Study Design Info

Allocation: N/A

Intervention Model: Single Group Assignment

Primary Purpose: Basic Science

Masking: None (Open Label)

Source: ClinicalTrials.gov