Effects of Canagliflozin on Intravascular Volume and Hemodynamics

NCT03190798 | Withdrawn Phase 4 DMC FDA Drug

• 2 other identifiers: HSC20170151HDIA4028
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Type2 Diabetes Mellitus; Cardiovascular Diseases

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• Change in Pulmonary capillary wedge pressure (PCWP)

  4 weeks

Study Arms (2)

Canagliflozin Group

ACTIVE COMPARATOR

Assuming a 25% dropout rate, 16 individuals in the canagliflozin group

Drug: Canagliflozin 300mg

Placebo Group

PLACEBO COMPARATOR

Assuming a 25% dropout rate, 11 individuals in the placebo group

Drug: Placebo

Interventions

Canagliflozin 300mg DRUG

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.

Also known as: Invokana

Canagliflozin Group

Placebo DRUG

Placebo for Canagliflozin

Also known as: Canagliflozin Placebo

Placebo Group

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

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

Study Sites (1)

The University of Texas Health Science Center at San Antonio

San Antonio, Texas, 78229, United States

Location

MeSH Terms

Conditions

Cardiovascular Diseases

Interventions

Canagliflozin

Intervention Hierarchy (Ancestors)

Thiophenes; Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Glucosides; Glycosides; Carbohydrates

Study Officials

• Devjit Tripathy, MD

  The University of Texas Health Science Center at San Antonio

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Randomized, Double-Blind, Placebo-Controlled, Single-Center, Mechanistic Study

Study Record Dates

• First Submitted: June 15, 2017
• First Posted: June 19, 2017
• Study Start: September 1, 2017
• Primary Completion: August 1, 2018
• Study Completion: August 1, 2018
• Last Updated: October 12, 2017

Record last verified: 2017-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)