Phase I Interaction Study of Istaroxime and Digoxin in Subjects With Stable Heart Failure

A Randomized, Double-blind, Placebo-controlled Escalating Dose Phase I Interaction Study to Evaluate the Pharmacokinetics, Tolerability and Pharmacodynamics of Three Dose Levels of Debio 0614 (Istaroxime) as a 24-hour Constant Rate IV Infusion in Combination With Chronic Oral Digoxin Treatment in Patients With Controlled Cardiac Failure and Decreased Left Ventricular Systolic Function

Status

Withdrawn

Phases

Phase 1

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00869115

Enrollment

Registered

2009-03-25

Start date

2009-06-30

Completion date

Unknown

Last updated

2014-10-23

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Heart Failure

Keywords

Digoxin, Inotropes, Lusitropic agents, Istaroxime, Debio 0614

Brief summary

This study explores a potential drug-drug interaction between istaroxime and digoxin in patients with stable CHF on chronic oral digoxin treatment.

Detailed description

This is a single center, randomized, double blind, placebo controlled, escalating dose phase I interaction study. The three dose levels of istaroxime or placebo will be randomized sequentially to three cohorts (I to III) of 16 patients each (12 patients on istaroxime and 4 patients on placebo). Digoxin will be administered non blinded in all patients, once daily in the morning after a standardized breakfast, continuing with previously personalized dosage schedule during the screening period, treatment period, post treatment period and follow up period. Prior to accrual of cohorts II and III, a Data Monitoring Committee (DMC) will advise on the continuation to the next istaroxime dose, based on a predetermined safety review. This 37 day study includes a screening period (Days -21 to -1), a treatment period (Day 1), a post treatment period (Days 2-4), and a follow up period (which includes one patient visit on Day 14). Patients will be confined in the phase I research center from Day -2 to Day 4.

Interventions

DRUGIstaroxime

Istaroxime 0.5 μg/kg/min (30 μg/kg/h) continuous i.v. infusion for 24 hours

Study design

Allocation

RANDOMIZED

Primary purpose

TREATMENT

Masking

QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

Main screening inclusion criteria : * Signed informed consent; * Male or female patients ≥18 years; * Female patients of childbearing potential must not be pregnant; * Chronic stable cardiac function impairment (no change in heart failure medication over the last 3 months and without any dosage adjustment in the last 4 weeks); * Systolic blood pressure (SBP) of ≥ 90 mmHg and ≤ 140 mmHg; * LVEF ≤ 35% by any method (to be performed at screening if not measured within the last 12 months); * Chronic treatment (i.e. once daily dosing without interruption) with oral digoxin started at least 3 months prior to study entry and without any concomitant administration of other positive inotropic drugs;

Exclusion criteria

Main screening

Design outcomes

Primary

Measure	Time frame
Pharmacokinetic endpoints : Istaroxime PK parameters: - Istaroxime and Istaroxime metabolites (PST2915/2922/3093) plasma concentrations - Istaroxime and Istaroxime metabolites (PST2915/2922/3093) urine concentrations	—
Pharmacokinetic endpoints : Digoxin PK parameters: - Digoxin plasma concentrations	—
Safety endpoints: - Incidence of adverse events; - Change in vital signs; - Change in 12-lead ECG parameters; - Incidence of clinically or hemodynamically significant episodes of supraventricular or ventricular arrhythmias detected by continuous EC	—
Pharmacodynamic endpoints: - Change in echocardiographic parameters; - Change in SBP; - Change in non invasive cardiac output (Impedance cardiography) parameters.	—

Outcome results

None listed

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026