Effects of Canagliflozin on Intravascular Volume and Hemodynamics

Cardiovascular Diseases Clinical Trial

Official title:

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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT03190798
• Other study ID #: HSC20170151H
• Secondary ID: DIA4028
• Status: Withdrawn
• Phase: Phase 4
• First received: June 15, 2017
• Last updated: October 10, 2017
• Start date: September 1, 2017
• Est. completion date: August 1, 2018

Study information

• Verified date: July 2017
• Source: The University of Texas Health Science Center at San Antonio
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: August 1, 2018
• Est. primary completion date: August 1, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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], ß-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

Related Conditions & MeSH terms

• Cardiovascular Diseases
• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Type2 Diabetes Mellitus

Intervention

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.
• Placebo
Placebo for Canagliflozin

Locations

Country	Name	City	State
United States	The University of Texas Health Science Center at San Antonio	San Antonio	Texas

Sponsors (2)

Lead Sponsor	Collaborator
The University of Texas Health Science Center at San Antonio	Janssen Scientific Affairs, LLC

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Change in Pulmonary capillary wedge pressure (PCWP)	The key secondary endpoint will be change in PCWP from baseline to 4 weeks.	4 weeks