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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00869115
Recruitment Status : Withdrawn (The study was not started due to a re-evaluation of the istaroxime development program)
First Posted : March 25, 2009
Last Update Posted : October 23, 2014
Information provided by:
Debiopharm International SA

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

Condition or disease Intervention/treatment Phase
Heart Failure Drug: Istaroxime Phase 1

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.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 0 participants
Allocation: Randomized
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 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
Study Start Date : June 2009

Resource links provided by the National Library of Medicine

Drug Information available for: Digoxin

Arm Intervention/treatment
Experimental: 1
TREATMENT 0.5 μg/kg/min
Drug: Istaroxime
Istaroxime 0.5 μg/kg/min (30 μg/kg/h) continuous i.v. infusion for 24 hours

Experimental: 2
TREATMENT 1.0 μg/kg/min
Drug: Istaroxime
Istaroxime 1.0 μg/kg/min (60 μg/kg/h) continuous i.v. infusion for 24 hours

Experimental: 3
TREATMENT 1.5 μg/kg/min
Drug: Istaroxime
Istaroxime 1.5 μg/kg/min (90 μg/kg/h) continuous i.v. infusion for 24 hours

Placebo Comparator: 4
Drug: Istaroxime
Placebo continuous i.v. infusion for 24 hours

Primary Outcome Measures :
  1. Pharmacokinetic endpoints : Istaroxime PK parameters: - Istaroxime and Istaroxime metabolites (PST2915/2922/3093) plasma concentrations - Istaroxime and Istaroxime metabolites (PST2915/2922/3093) urine concentrations
  2. Pharmacokinetic endpoints : Digoxin PK parameters: - Digoxin plasma concentrations
  3. 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
  4. Pharmacodynamic endpoints: - Change in echocardiographic parameters; - Change in SBP; - Change in non invasive cardiac output (Impedance cardiography) parameters.

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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 exclusion criteria :

  • Need for current or intermittent intravenous positive inotrope administration within the preceding 6 months, or hemodynamic support devices;
  • Acute coronary syndrome within the past 3 months;
  • Coronary artery bypass graft or percutaneous coronary intervention within the past 3 months;
  • Stroke within the past 6 months;
  • Atrial fibrillation or uncontrolled heart rate (HR) (> 100 beats per minute [bpm]);
  • Significant arrhythmia or second or third degree atrio-ventricular block;
  • Valvular disease as the primary cause of HF;
  • Significant ECG abnormalities as assessed by appropriately qualified physician or investigator including QTcF >450;
  • Positive testing for Human Immunodeficiency Virus (HIV), Hepatitis B and/or Hepatitis C;

Main randomization exclusion criteria:

  • HR > 100 bpm or < 50 bpm;
  • Serum potassium > 5.3 mmol/L or < 3.8 mmol/L and magnesium > 1.1 mmol/L or < 0.6 mmol/L,
  • TN I > ULN.

Additional Information:
Responsible Party: Hein Van Ingen, Medical Director, Debiopharm S.A. Identifier: NCT00869115     History of Changes
Other Study ID Numbers: Debio 0614-106
PAREXEL Study Number : 98378
First Posted: March 25, 2009    Key Record Dates
Last Update Posted: October 23, 2014
Last Verified: October 2014

Keywords provided by Debiopharm International SA:
Lusitropic agents
Debio 0614

Additional relevant MeSH terms:
Heart Failure
Heart Diseases
Cardiovascular Diseases
Anti-Arrhythmia Agents
Cardiotonic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Protective Agents
Physiological Effects of Drugs