Heart FailurePhase 1NCT00869115
Phase I Interaction Study of Istaroxime and Digoxin in Subjects With Stable Heart Failure
A Phase 1 study testing Istaroxime in people with Heart Failure, run by Debiopharm International SA.
Trial summary
This study explores a potential drug-drug interaction between istaroxime and digoxin in patients with stable CHF on chronic oral digoxin treatment. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Heart Failure
- What is being tested?
- Istaroxime
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- Jun 2009to not given
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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;
Who cannot join
- 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]);
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- 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.
About this study
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
This study explores a potential drug-drug interaction between istaroxime and digoxin in patients with stable CHF on chronic oral digoxin treatment.
Read the 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.
- Conditions
- Heart Failure
- Being tested
- Istaroxime
- Keywords
- Digoxin, Inotropes, Lusitropic agents, Istaroxime, Debio 0614
- Medical subject headings
- Heart Failure
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IstaroximeDrug
Istaroxime 0.5 μg/kg/min (30 μg/kg/h) continuous i.v. infusion for 24 hours
IstaroximeDrug
Istaroxime 1.0 μg/kg/min (60 μg/kg/h) continuous i.v. infusion for 24 hours
IstaroximeDrug
Istaroxime 1.5 μg/kg/min (90 μg/kg/h) continuous i.v. infusion for 24 hours
IstaroximeDrug
Placebo continuous i.v. infusion for 24 hours
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | TREATMENT 0.5 μg/kg/min Receives: Drug: Istaroxime |
| 2 | Experimental | TREATMENT 1.0 μg/kg/min Receives: Drug: Istaroxime |
| 3 | Experimental | TREATMENT 1.5 μg/kg/min Receives: Drug: Istaroxime |
| 4 | Placebo comparator | PLACEBO Receives: Drug: Istaroxime |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Mar 2009 (estimated)
- Study startJun 2009
Why it stopped: The study was not started due to a re-evaluation of the istaroxime development program
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Heart FailureStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Debiopharm International SA
- Sponsor type
- Industry (pharma, biotech, devices)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00869115
- Sponsor's protocol ID
- Debio 0614-106
- Other IDs
- PAREXEL Study Number : 98378
- Status last verified
- Oct 2014
- First submitted
- 24 Mar 2009
- Last updated
- 23 Oct 2014
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Gheorghiade M, Blair JE, Filippatos GS, Macarie C, Ruzyllo W, Korewicki J, Bubenek-Turconi SI, Ceracchi M, Bianchetti M, Carminati P, Kremastinos D, Valentini G, Sabbah HN; HORIZON-HF Investigators. Hemodynamic, echocardiographic, and neurohormonal effects of istaroxime, a novel intravenous inotropic and lusitropic agent: a randomized controlled trial in patients hospitalized with heart failure. J Am Coll Cardiol. 2008 Jun 10;51(23):2276-85. doi: 10.1016/j.jacc.2008.03.015. Epub 2008 Apr 9.
PubMed 18534276
Study at a glance
From the registry record, last updated by the sponsor on 23 Oct 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00869115
- Acronym / sponsor ID
- Debio 0614-106
- Conditions
- Heart Failure
- Keywords
- Digoxin, Inotropes, Lusitropic agents, Istaroxime, Debio 0614
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: The study was not started due to a re-evaluation of the istaroxime development program
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Debiopharm International SAIndustry (pharma, biotech, devices)
- Study start
- Jun 2009
- First posted
- 25 Mar 2009 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: IstaroximeTREATMENT 0.5 μg/kg/min |
| 2 | Experimental | Drug: IstaroximeTREATMENT 1.0 μg/kg/min |
| 3 | Experimental | Drug: IstaroximeTREATMENT 1.5 μg/kg/min |
| 4 | Placebo comparator | Drug: IstaroximePLACEBO |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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;
Key exclusion criteria (14 listed)
- 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]);
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| IstaroximeIstaroxime 0.5 μg/kg/min (30 μg/kg/h) continuous i.v. infusion for 24 hours | Drug | 1 |
| IstaroximeIstaroxime 1.0 μg/kg/min (60 μg/kg/h) continuous i.v. infusion for 24 hours | Drug | 2 |
| IstaroximeIstaroxime 1.5 μg/kg/min (90 μg/kg/h) continuous i.v. infusion for 24 hours | Drug | 3 |
| IstaroximePlacebo continuous i.v. infusion for 24 hours | Drug | 4 |
Primary outcome
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.
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Oct 2014.
- Background: PubMed 18534276Gheorghiade M, Blair JE, Filippatos GS, Macarie C, Ruzyllo W, Korewicki J, Bubenek-Turconi SI, Ceracchi M, Bianchetti M, Carminati P, Kremastinos D, Valentini G, Sabbah HN; HORIZON-HF Investigators. Hemodynamic, echocardiographic, and neurohormonal effects of istaroxime, a novel intravenous inotropic and lusitropic agent: a randomized controlled trial in patients hospitalized with heart failure. J Am Coll Cardiol. 2008 Jun 10;51(23):2276-85. doi: 10.1016/j.jacc.2008.03.015. Epub 2008 Apr 9.
- Related InfoLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Istaroxime in people with Heart Failure, run by Debiopharm International SA.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 23 Oct 2014. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Pharmacokinetic endpoints : Istaroxime PK parameters: - Istaroxime and Istaroxime metabolites (PST2915/2922/3093) plasma concentrations - Istaroxime and Istaroxime metabolites (PST2915/2922/3093) urine concentrations. The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00869115, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Oct 2014.