A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study to Investigate the Safety, Tolerability, Pharmacodynamics and Pharmacokinetics of JNJ-39588146 in Subjects with Heart Failure - N/A

• Register: EUCTR
• Last refreshed on: 21 August 2017
• Main ID: EUCTR2009-013929-42-BE
• Date of registration: 23/02/2010
• Prospective Registration: Yes
• Primary sponsor: Janssen-Cilag International NV
• Public title: A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study to Investigate the Safety, Tolerability, Pharmacodynamics and Pharmacokinetics of JNJ-39588146 in Subjects with Heart Failure - N/A
• Scientific title: A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study to Investigate the Safety, Tolerability, Pharmacodynamics and Pharmacokinetics of JNJ-39588146 in Subjects with Heart Failure - N/A
• Date of first enrolment: 03/05/2010
• Target sample size: 60
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2009-013929-42
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Belgium, Germany, Italy

Key inclusion & exclusion criteria

Inclusion criteria:
1. Subjects must have signed an informed consent document indicating that they
understand the purpose of the study and the procedures required for the study and are willing to participate in the study.

2a. Subjects must have systolic dysfunction (LVEF =0.35, documented within the
6 months prior to dosing by any quantitative method) and Heart Failure (New York
Heart Association [NYHA] functional class II-IV). Subjects considered by the
principal investigator as having end-stage or refractory heart failure characterized by
severe cachexia, restriction to bed rest, hospice status or are in imminent need (within the next 30 days) of a left ventricular assist device or heart transplant should not be considered for the study.

2b. Have a pulmonary capillary wedge pressure =20 mm Hg immediately prior to the initiation of the infusion (average of 3 measurements).

3. Have a cardiac index =2.5 L/min/m2 immediately prior to the initiation of the
infusion (average of 3 measurements).

4. Subjects must have supine blood pressure (after resting for 5 min) between the range of 95 - 160 mm Hg systolic (inclusive), and 50 - 89 mm Hg diastolic (inclusive) at screening and Day 1 pre-dose.

5. Criterion modified per amendment
5.1 Must not have received intravenous heart failure medications including inotropes,
vasodilators or diuretics, for at least 18 hours prior to initiation of study
infusion. Subjects requiring intravenous medications to control their heart
failure (such as inotropes and/or vasodilators within the next 48 hours and/or
diuretics within the next 24 hours) should not participate in the study. If there is
a planned elective evaluation of a subject’s cardiac response to
inotropes/vasodilators, they may participate in the study if the planned elective
treatment with these agents is =4 hours after the end of the study drug infusion.

6. Criterion modified per amendment
6.1 Serum potassium within normal limits confirmed within 2 week of the study drug
infusion. If there has been a change in diuretic therapy within these past 2
weeks, serum potassium must be within normal limits within 24 hours of dosing.

7. Criterion modified per amendment
7.1 Subjects must have a body mass index (BMI) between 18 to 35 kg/m2 (inclusive)
and with a minimum body weight of 50 kg.

8. Female subjects must be of non-childbearing potential, defined as either being:
- postmenopausal (for at least 24 months) or,
- surgically sterile for more than 6 months prior to participation in the study
(have had a hysterectomy or bilateral oophorectomy, tubal ligation, or
otherwise be incapable of pregnancy), and must have a negative serum ß-human chorionic gonadotropin (ß-hCG) pregnancy test at screening; and a negative urine pregnancy test on admission to the clinical study unit.

9. Male subjects must consent to utilize a medically acceptable method of contraception throughout the study and for 3 months after the last dose of study drug and to not donate sperm during the study and for 3 months after receiving the last dose of study drug. Medically acceptable methods of contraception that may be used by the subject and/or the partner include double barrier method (condom, diaphragm, or cervical cap used with intravaginal spermicidal foam, cream, or gel), IUD, surgical sterilization (6 months post surgery), post-menopausal partner (not experiencing a menstrual period for a minimum of two years) and hormonal contraceptives (which must be used consistently for 3 months prior t
Exclusion criteria:
1. Subjects without bundle branch block with confirmed screening QTcF interval >450
msec in males or > 470 msec in females. Subjects with bundle branch block or
receiving amiodarone with confirmed screening QTcF interval >500 msec. Subjects
with a history of additional risk factors for torsades de pointe (eg, hypokalemia, family history of Long QT Syndrome), or the use of concomitant medications that
prolong the QT/QTc interval.

2. Subjects with atrial fibrillation, sinus tachycardia, sustained ventricular tachycardia,
ventricular fibrillation within the last 30 days or third degree heart block at screening
or check-in.

3. Subjects with a resting heart rate less than 50 or greater than 100 beats per minute (via ECG output pre-dose).

4. Criterion modified per amendment
4.1 Acute coronary syndrome, myocardial infarction or coronary revascularization
(CABG or percutaneous coronary intervention) within 1 month or history of
resuscitated sudden death or systemic shock.

5. Subjects with a left-ventricular assist device or heart transplant or mechanical
ventilation.

6. Subjects with hemodynamically-significant primary valvular heart disease.

7. Subjects with serum digoxin concentrations (minimum levels) >1.5 ng/ml at
screening.

8. Subjects in whom the PA catheter is being placed solely for study measurements,
with an INR >1.5 when femoral, subclavian or jugular approach is used.

9. History of transient ischemic attack within the 6 months before screening.

10. History of clinically significant chronic hepatic, reproductive, gastrointestinal,
primary renal, hematologic, pulmonary, neurologic, respiratory or psychiatric
disorders, and oncologic conditions or acute or chronic infection.

11. Subjects with uncontrolled hypertension or/and uncontrolled diabetes.

12. Criterion modified per amendment
12.1 Subjects with ALT or AST greater than 3 times the upper limit of normal at
screening may not participate in the study.

13. Subjects with creatinine clearance <30 mL/min at screening or subjects requiring dialysis or serum ultra-filtration.

14. Any condition that, in the opinion of the Investigator, would compromise the well
being of the subject or the study or prevent the subject from meeting or performing
study requirements.

15. Subjects for which there is a concern of right intra-ventricular lead displacement
including subjects who have had placement of pacemaker or ICD within the past
3 months before screening.

16. Subjects with heart failure caused by myositis, lung disease, congenital heart disease, constrictive pericarditis, or hypertrophic or restrictive cardiomyopathy.

17. Subjects planning to parent a child during the study or within 3 months after the last dose of study drug.

18. Pregnant or breast-feeding females.

19. Employees of the Investigator or study center, with direct involvement in the
proposed study or other studies under the direction of that Investigator or study
center, as well as family members of the employees or the Investigator.

20. Known allergies, hypersensitivity, or intolerance to JNJ-39588146 or its excipients
(refer to Section 14.1, Physical Description of Study Drug(s)), or urocortin or
urocortin 2.

21. Received an investigational drug (including vaccines) or used an investigational
medical device within 30 days before the planned start of treatment, or within a
period of less than ten times the drug’s half-life, whichever is longer.

22. Subjects who have donated blood or plasma, or have had blo

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

JNJ-39588146 is being developed for the treatment of heart failure.
MedDRA version: 12.1 Level: LLT Classification code 10019279 Term: Heart failure

Intervention(s)

Product Name: JNJ-39588146 - solution for infusion - 0.2 mg/mL
Product Code: JNJ-39588146
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: not assigned
CAS Number: not assigned
Current Sponsor code: JNJ-39588146
Other descriptive name: Stresscopin Acetate
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 0.2-
Pharmaceutical form of the placebo: Solution for infusion
Route of administration of the placebo: Intravenous use

Primary Outcome(s)

Primary end point(s): Two primary endpoints are the post-baseline changes (at 1-hour, 2 hours and 3 hours post infusion initiation) in pulmonary capillary wedge pressure and cardiac index. The two primary endpoints will be used separately to compare JNJ-39588146 with placebo.

Main Objective: Assess the hemodynamic effects, the safety and the tolerability of JNJ-39588146 when administered by intravenous infusion to male subjects and female subjects of non-childbearing potential with New York Heart Association (NYHA) Class II-IV heart failure.

Secondary Objective: Characterize the pharmacokinetics of JNJ-39588146 in subjects with heart failure.

Secondary ID(s)

2009-013929-42-DE

N/A

39588146AHF2001