NCT02891954

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.

Trial Health

83
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
700

participants targeted

Target at P75+ for phase_1 diabetes-mellitus-type-2

Timeline
8mo left

Started Sep 2016

Longer than P75 for phase_1 diabetes-mellitus-type-2

Status
active not recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress94%
Sep 2016Dec 2026

First Submitted

Initial submission to the registry

August 30, 2016

Completed
2 days until next milestone

Study Start

First participant enrolled

September 1, 2016

Completed
7 days until next milestone

First Posted

Study publicly available on registry

September 8, 2016

Completed
7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

September 25, 2023

Completed
3.3 years until next milestone

Study Completion

Last participant's last visit for all outcomes

December 25, 2026

Expected
Last Updated

December 18, 2025

Status Verified

December 1, 2025

Enrollment Period

7.1 years

First QC Date

August 30, 2016

Last Update Submit

December 16, 2025

Conditions

Diabetes Mellitus, Type 2

Keywords

GlucosuriaSGLT2 inhibitorsCanagliflozinFGF23Parathyroid hormone1,25-Dihydroxyvitamin DGlucagonKetone bodiesUric acidPharmacogenomics

Outcome Measures

Primary Outcomes (1)

  • Urinary glucose excretion (during the time interval 24-48 hours after first administration of canagliflozin)

    Urine collection will be initiated 24 hours after initiation of canagliflozin treatment, and continued for an additional 24 hours.

    24-48 hours

Secondary Outcomes (6)

  • 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

  • +1 more secondary outcomes

Study Arms (1)

Single arm

EXPERIMENTAL

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

Drug: Canagliflozin

Interventions

CanagliflozinDRUG

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

Also known as: Invokana (brand name for canagliflozin)
Single arm

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Of Amish descent
  • Age 18 or older
  • BMI: 18-40 kg/m2

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Related Publications (9)

  • Taylor SI, Blau JE, Rother KI. Possible adverse effects of SGLT2 inhibitors on bone. Lancet Diabetes Endocrinol. 2015 Jan;3(1):8-10. doi: 10.1016/S2213-8587(14)70227-X. Epub 2014 Dec 16. No abstract available.

    PMID: 25523498BACKGROUND

  • Taylor SI, Blau JE, Rother KI. SGLT2 Inhibitors May Predispose to Ketoacidosis. J Clin Endocrinol Metab. 2015 Aug;100(8):2849-52. doi: 10.1210/jc.2015-1884. Epub 2015 Jun 18.

    PMID: 26086329BACKGROUND

  • Blau JE, Bauman V, Conway EM, Piaggi P, Walter MF, Wright EC, Bernstein S, Courville AB, Collins MT, Rother KI, Taylor SI. Canagliflozin triggers the FGF23/1,25-dihydroxyvitamin D/PTH axis in healthy volunteers in a randomized crossover study. JCI Insight. 2018 Apr 19;3(8):e99123. doi: 10.1172/jci.insight.99123. eCollection 2018 Apr 19.

    PMID: 29669938BACKGROUND

  • Blau JE, Taylor SI. Adverse effects of SGLT2 inhibitors on bone health. Nat Rev Nephrol. 2018 Aug;14(8):473-474. doi: 10.1038/s41581-018-0028-0.

    PMID: 29875481BACKGROUND

  • Beitelshees AL, Leslie BR, Taylor SI. Sodium-Glucose Cotransporter 2 Inhibitors: A Case Study in Translational Research. Diabetes. 2019 Jun;68(6):1109-1120. doi: 10.2337/dbi18-0006.

    PMID: 31109940BACKGROUND

  • Shahidzadeh Yazdi Z, Streeten EA, Whitlatch HB, Montasser ME, Beitelshees AL, Taylor SI. Vitamin D Deficiency Increases Vulnerability to Canagliflozin-induced Adverse Effects on 1,25-Dihydroxyvitamin D and PTH. J Clin Endocrinol Metab. 2024 Jan 18;109(2):e646-e656. doi: 10.1210/clinem/dgad554.

    PMID: 37738423RESULT

  • Shahidzadeh Yazdi Z, Streeten EA, Whitlatch HB, Montasser ME, Beitelshees AL, Taylor SI. Critical Role for 24-Hydroxylation in Homeostatic Regulation of Vitamin D Metabolism. J Clin Endocrinol Metab. 2025 Jan 21;110(2):e443-e455. doi: 10.1210/clinem/dgae156.

    PMID: 38481375RESULT

  • Shahidzadeh Yazdi Z, Streeten EA, Whitlatch HB, Bargal SA, Beitelshees AL, Taylor SI. Value of Vitamin D Metabolite Ratios in 3 Patients as Diagnostic Criteria to Assess Vitamin D Status. JCEM Case Rep. 2024 Jun 28;2(7):luae095. doi: 10.1210/jcemcr/luae095. eCollection 2024 Jul.

    PMID: 38947416RESULT

  • Taylor SI, Cherng HR, Shahidzadeh Yazdi Z, Montasser ME, Whitlatch HB, Mitchell BD, Shuldiner AR, Streeten EA, Beitelshees AL. Pharmacogenetics of sodium-glucose co-transporter-2 inhibitors: Validation of a sex-agnostic pharmacodynamic biomarker. Diabetes Obes Metab. 2023 Dec;25(12):3512-3520. doi: 10.1111/dom.15246. Epub 2023 Aug 22.

    PMID: 37608471DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 2Glycosuria

Interventions

Canagliflozin

Condition Hierarchy (Ancestors)

Diabetes MellitusGlucose Metabolism DisordersMetabolic DiseasesNutritional and Metabolic DiseasesEndocrine System DiseasesUrination DisordersUrologic DiseasesFemale Urogenital DiseasesFemale Urogenital Diseases and Pregnancy ComplicationsUrogenital DiseasesMale Urogenital Diseases

Intervention Hierarchy (Ancestors)

ThiophenesSulfur CompoundsOrganic ChemicalsHeterocyclic Compounds, 1-RingHeterocyclic CompoundsGlucosidesGlycosidesCarbohydrates

Study Officials

  • Simeon I Taylor, MD, PhD

    Unversity of Maryland School of Medicine

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NA
Masking
NONE
Purpose
BASIC SCIENCE
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Professor of Medicine

Study Record Dates

First Submitted

August 30, 2016

First Posted

September 8, 2016

Study Start

September 1, 2016

Primary Completion

September 25, 2023

Study Completion (Estimated)

December 25, 2026

Last Updated

December 18, 2025

Record last verified: 2025-12

Data Sharing

IPD Sharing
Will not share