Safety and Hemodynamic Effects and Pharmacokinetics of CXL-1020 in Patients With Stable Heart Failure

NCT01092325 | Completed Phase 1 DMC

• 1 other identifier: CXL-1020-01
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

Brief Summary

A Phase 1-2a Study of CXL-1020-01 in Patients with Stable Heart Failure

Conditions

Heart Failure

Keywords

Heart Failure

Outcome Measures

Primary Outcomes (1)

• Safety and Tolerability

  Safety is measured by assessment of multiple parameters including standard laboratory safety, changes in blood pressure and heart rate, changes in electrocardiogram, monitoring of heart rhythm via holter monitor, measurement of cardiac safety biomarkers such as plasma troponin as well as treatment emergent adverse events

  From initial exposure to 30 days following exposure

Secondary Outcomes (2)

• Hemodynamic Effects as Measured by Impedance Cardiography and Echocardiography

  before during and following the infusion of study medication

• Plasma and Urinary Pharmacokinetics

  From start of infusion until 18 hours post infusion

Study Arms (6)

Cohort 1 CXL-1020

EXPERIMENTAL

An intravenous infusion of CXL-1020 administered for a total of 4 hours over a total of 3 occasions separated by at least one week. Each of the 3 doses of CXL-1020 are different, starting with the lowest dose and increasing to the highest dose.

Drug: CXL-1020

Cohort 1 Placebo

PLACEBO COMPARATOR

A 4 hour infusion of Placebo administered one time randomly among the 3 active doses of CXL-1020 in cohort 1

Drug: Placebo for CXL-1020 Cohort 1

Cohort 2 CXL-1020

EXPERIMENTAL

An intravenous infusion of CXL-1020 administered for a total of 4 hours over a total of 3 occasions separated by at least one week. Each of the 3 doses of CXL-1020 are different, starting with the lowest dose and increasing to the highest dose.

Drug: CXL-1020

Cohort 2 Placebo

PLACEBO COMPARATOR

A 4 hour infusion of Placebo administered one time randomly among the 3 active doses of CXL-1020 in cohort 1

Drug: Placebo for CXL-1020 Cohort 2

Echo Cohort A CXL-1020

ACTIVE COMPARATOR

A 4 hour infusion of a fixed dose of CXL-1020 which was studied in Cohort 1 or Cohort 2 which is expected to be well tolerated and have hemodynamic effect

Drug: CXL-1020 Dose for Echo Cohort A

Echo Cohort B CXL-1020

ACTIVE COMPARATOR

CXL-1020 administered at a fixed rate for the initial 2 hours and at a higher fixed rate for the last 2 hours of a 4 hour infusion at doses which were studied in Cohort 1 or Cohort 2 and expected to be well tolerated and have hemodynamic effects

Drug: CXL-1020 Doses for Echo Cohort B

Interventions

CXL-1020 DRUG

Intravenous infusion of one of 3 active dosages of CXL-1020

Cohort 1 CXL-1020

Placebo for CXL-1020 Cohort 1 DRUG

A 4 hour infusion of a IV solution containing 5% Dextrose in water (Sugar Water)

Cohort 1 Placebo

Placebo for CXL-1020 Cohort 2 DRUG

A 4 hour infusion of a IV solution containing 5% Dextrose in water (Sugar Water)

Cohort 2 Placebo

CXL-1020 Dose for Echo Cohort A DRUG

A 4 hour fixed dose of CXL-1020 which was studied in Cohort 1 or 2 which was demonstrated to be safe and well tolerated and have some anticipated hemodynamic effect

Echo Cohort A CXL-1020

CXL-1020 Doses for Echo Cohort B DRUG

A 2 hour dose level of CXL-1020 which was studied in Cohort 1 or 2 which was demonstrated to be safe and well tolerated and have some anticipated hemodynamic effect followed by another higher 2 hour dose level of CXL-1020 which was studied in Cohort 1 or 2 which was demonstrated to be safe and well tolerated and have some anticipated hemodynamic effect

Echo Cohort B CXL-1020

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• In order to be eligible for randomization, a patient MUST:
• Be a male or post menopausal or surgically sterile female outpatient between 18 and 85 years of age
• Have chronic Systolic HF due to primary/idiopathic dilated cardiomyopathy, coronary artery disease or hypertension, and stable for at least 30 days prior to screening
• Have a core echo lab confirmed left ventricular ejection fraction ≤ 40% in a baseline 2D-Echocardiogram prior to and within 60 days of the first dose of study medication with evidence of at least minimal LV dilation on the basis of an observed LV-EDV index that is above normal
• Have a baseline NT-Pro-BNP of greater than or equal to the top of the normal reference range (124pg/ml) prior to and within 60 days of the first dose of study medication
• Be on unchanging doses of HF medications (with exception of diuretic dosage) for 2 weeks prior to randomization without planned initiation of new hemodynamically active therapy during the conduct of the study
• Be capable of understanding the nature of the trial and be willing to participate as documented by written informed consent
• Be willing and able to comply with the study protocol requirements for the duration of the study, including pharmacokinetic sampling
• If a post-menopausal or surgically sterile female, confirmation of sterility status (Post menopausal or surgically sterile for at least 6 months) - (Post-menopausal subjects will require a urine pregnancy test for confirmation prior to enrollment and urine pregnancy tests prior to each dosing)
• If a fertile male, must be using 2 approved contraceptive methods (a condom and a spermicidal agent, even if the partner is using birth control) for the duration of the study and for 3 months following participation in the study and further agree to not donate sperm for 3 months after participation in the study. Must have a negative urine test for drugs of abuse and a negative ethanol breath test at screening and before each dosing period

You may not qualify if:

• In order to be eligible for randomization, a patient MUST NOT:
• Have participated in any investigational drug study within 30 days preceding randomization or have previously received therapy with CXL-1020
• Have a heart rate \<50 or ≥ 90 BPM at baseline prior to randomization.
• Have a blood pressure \>150 Systolic and/or \>90 diastolic mmHg at baseline prior to randomization
• Have a systolic blood pressure of less than 100 mmHg at baseline prior to randomization
• Have QT/QTc prolongation \> 460 msec or \> 500msec in patients with preexisting bundle branch block (only applies to non-paced patients in sinus rhythm)
• Have experienced a documented symptomatic or electrocardiographically recorded episode of atrial fibrillation/flutter within 60 days before screening and be in normal sinus rhythm at each baseline before study drug is administered
• Have a history of sustained or hemodynamically significant VT or VF requiring cardioversion, or self-terminating VT associated with hypotension
• Have non-sustained VT (HR \> 120 bpm) of 10 beats or more during monitoring in the baseline monitoring period prior to each dose of study medication, or in any Holter or EKG recording within 1 year of first dose of study medication.
• Have a weight or height that exceeds the specifications for the ICG Device of (greater than 341 pounds or taller than 7 feet 2 inches.)
• Be post-successful cardiac resuscitation
• Have a history of worsening HF within 30 days prior to screening as defined by:
• Unscheduled ER or clinic visits relating to HF or hospital admission for management of HF
• Treatment with intravenous inotropic or vasodilator drugs
• Be diagnosed with acute coronary syndrome or acute myocardial infarction within three months prior to screening

Sponsors & Collaborators

• Bristol-Myers Squibb: lead
• Cardioxyl Pharmaceuticals, Inc: collaborator

Study Sites (1)

Orange County Clinical Research Center

Tustin, California, 92780, United States

Location

Related Publications (2)

• A Phase I/IIa First in Man Safety and Tolerability Study of a Novel HNO Donor, CXL-1020, in Patients with Stable Congestive Heart Failure. Monday, April 4, 2011; 9:30 a.m. - 12:30 p.m., Ernest N. Morial Convention Center, Hall F; Poster Board #42

  RESULT

• Sabbah HN, Tocchetti CG, Wang M, Daya S, Gupta RC, Tunin RS, Mazhari R, Takimoto E, Paolocci N, Cowart D, Colucci WS, Kass DA. Nitroxyl (HNO): A novel approach for the acute treatment of heart failure. Circ Heart Fail. 2013 Nov;6(6):1250-8. doi: 10.1161/CIRCHEARTFAILURE.113.000632. Epub 2013 Oct 9.

  PMID: 24107588 DERIVED

MeSH Terms

Conditions

Heart Failure

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

Study Officials

• Doug Cowart, Pharm D.

  Cardioxyl Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 23, 2010
• First Posted: March 24, 2010
• Study Start: June 1, 2009
• Primary Completion: May 1, 2010
• Study Completion: May 1, 2010
• Last Updated: July 1, 2016

Record last verified: 2016-06

Locations

US (1)