Effects of Canagliflozin on Intravascular Volume and Hemodynamics

A Randomized, Double-Blind, Placebo-Controlled, Single-Center, Mechanistic Study to Evaluate the Effects of Canagliflozin on Intravascular Volume and Hemodynamics in Subjects With Type 2 Diabetes Mellitus and Heart Failure

RESEARCH HYPOTHESIS

• In subjects with T2DM and HF, effect of canagliflozin will be superior to placebo for the change from baseline in PCWP after a single dose (6 hours post-dose) and after 4 weeks.
• Treatment with canagliflozin will be well tolerated over 4 weeks.

Study Overview

• Status: Withdrawn
• Conditions: Cardiovascular Diseases; Type2 Diabetes Mellitus
• Intervention / Treatment: Drug: Canagliflozin 300mg; Drug: Placebo

Detailed Description

This is a randomized, double-blind, placebo-controlled, parallel-group, single-center study (Figure 1). Thirty subjects will be randomized in a 3:2 randomization ratio to canagliflozin 300 mg once daily (QD) or placebo. The study will include a 3-week pretreatment screening phase and a 4-week double-blind treatment phase.

• Study Type: Interventional
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Texas
    • San Antonio, Texas, United States, 78229
      • The University of Texas Health Science Center at San Antonio

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• on stable doses (more than 3 months) of antihyperglycemic agents (except for an SGLT2 inhibitor and insulin)
• have an A1c ≥7% and ≤11%
• Estimated glomerular filtration rate (eGFR) must be ≥45 ml/min•1.73 m2
• have an NT-proBNP ≥500 pg/mL
• be on a stable dose of guideline-directed HF medication (i.e., angiotensin converting enzyme [ACE] inhibitor, angiotensin II receptor blocker [ARB], or angiotensin receptor neprilysin inhibitor [ARNI], β-blocker, diuretics, and/or mineralcorticoid receptor antagonist) for at least 4 weeks
• be on stable antihypertensive therapy for at least 2 months

Exclusion Criteria:

• T1DM
• repeated fasting plasma glucose (FPG) or fasting self-monitored blood glucose measurements ≥240 mg/dL or both
• during the pretreatment phase, NYHA Class IV HF status, uncontrolled hypertension as defined as systolic blood pressure (SBP) >160 or diastolic blood pressure (DBP) >100 mmHg
• liver disease (ALT or AST >3 x ULN)
• anemia Hb<10
• anticipated cardiac surgery or coronary intervention within the next 3 months
• severe unremediated valvular heart disease
• major CV event (e.g., MI, cerebrovascular accident) within 3 months prior to screening visit
• hospitalization for HF within 2 months prior to screening visit
• documented atrial fibrillation
• history of atraumatic amputation within past 12 months of screening or critical ischemia of the lower extremity within 6 months of screening
• an active skin ulcer, osteomyelitis, or gangrene
• have an allergy to iodocyanine green and inulin

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Canagliflozin Group; Assuming a 25% dropout rate, 16 individuals in the canagliflozin group	Drug: Canagliflozin 300mg; Canagliflozin is a sodium-glucose cotransporter 2 (SGLT2) inhibitor. It works by decreasing the amount of sugar the body absorbs, and increasing the amount of sugar that leaves the body in the urine. Administered in 300mg tablets.; Other Names: Invokana
Placebo Comparator: Placebo Group; Assuming a 25% dropout rate, 11 individuals in the placebo group	Drug: Placebo; Placebo for Canagliflozin; Other Names: Canagliflozin Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Pulmonary capillary wedge pressure (PCWP)	The primary efficacy endpoint will be change in PCWP from baseline to end of acute administration monitoring period (6 hours).	6 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Pulmonary capillary wedge pressure (PCWP)	The key secondary endpoint will be change in PCWP from baseline to 4 weeks.	4 weeks

Collaborators and Investigators

• Sponsor: The University of Texas Health Science Center at San Antonio
• Collaborators: Janssen Scientific Affairs, LLC

Study record dates

Study Major Dates

• Study Start (Anticipated): September 1, 2017
• Primary Completion (Anticipated): August 1, 2018
• Study Completion (Anticipated): August 1, 2018

Study Registration Dates

• First Submitted: June 15, 2017
• First Submitted That Met QC Criteria: June 15, 2017
• First Posted (Actual): June 19, 2017

Study Record Updates

• Last Update Posted (Actual): October 12, 2017
• Last Update Submitted That Met QC Criteria: October 10, 2017
• Last Verified: July 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Cardiovascular Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Sodium-Glucose Transporter 2 Inhibitors; Canagliflozin
• Other Study ID Numbers: HSC20170151H; DIA4028 (Other Grant/Funding Number: Janssen)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No