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

This study has been withdrawn prior to enrollment.
(The study was not started due to a re-evaluation of the istaroxime development program)
Sponsor:
Information provided by:
Debiopharm International SA
ClinicalTrials.gov Identifier:
NCT00869115
First received: March 24, 2009
Last updated: November 2, 2009
Last verified: November 2009
  Purpose

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


Condition Intervention Phase
Heart Failure
Drug: Istaroxime
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Masking: Double Blind (Subject, Caregiver, 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

Resource links provided by NLM:


Further study details as provided by Debiopharm International SA:

Primary Outcome Measures:
  • Pharmacokinetic endpoints : Istaroxime PK parameters: - Istaroxime and Istaroxime metabolites (PST2915/2922/3093) plasma concentrations - Istaroxime and Istaroxime metabolites (PST2915/2922/3093) urine concentrations [ Designated as safety issue: No ]
  • Pharmacokinetic endpoints : Digoxin PK parameters: - Digoxin plasma concentrations [ Designated as safety issue: No ]
  • 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 [ Designated as safety issue: No ]
  • Pharmacodynamic endpoints: - Change in echocardiographic parameters; - Change in SBP; - Change in non invasive cardiac output (Impedance cardiography) parameters. [ Designated as safety issue: No ]

Estimated Enrollment: 48
Study Start Date: June 2009
Arms Assigned Interventions
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
PLACEBO
Drug: Istaroxime
Placebo continuous i.v. infusion for 24 hours

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
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, see Learn About Clinical Studies.

No Contacts or Locations Provided
  More Information

Additional Information:
Publications:
Responsible Party: Hein Van Ingen, Medical Director, Debiopharm S.A.
ClinicalTrials.gov Identifier: NCT00869115     History of Changes
Other Study ID Numbers: Debio 0614-106, PAREXEL Study Number : 98378
Study First Received: March 24, 2009
Last Updated: November 2, 2009
Health Authority: South Africa: Medicines Control Council
United States: Food and Drug Administration

Keywords provided by Debiopharm International SA:
Digoxin
Inotropes
Lusitropic agents
Istaroxime
Debio 0614

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

ClinicalTrials.gov processed this record on August 26, 2014