Clinical Trials Register

Summary
EudraCT Number:	2008-008384-10
Sponsor's Protocol Code Number:	NIL-CDNP-CT005
National Competent Authority:	Germany - BfArM
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2009-03-03
Trial results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Germany - BfArM

A.2

EudraCT number

2008-008384-10

A.3

Full title of the trial

A MULTI CENTER, SINGLE‐BLIND, PLACEBO‐CONTROLLED PHASE 2
STUDY ASSESSING THE SAFETY AND EFFICACY OF INTRAVENOUS CD‐NP
IN THE TREATMENT OF PATIENTS WITH ACUTE DECOMPENSATED
HEART FAILURE (ADHF)

A.3.2

Name or abbreviated title of the trial where available

NIL-CDNP-CT005

A.4.1

Sponsor's protocol code number

NIL-CDNP-CT005

A.7

Trial is part of a Paediatric Investigation Plan

Information not present in EudraCT

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Nile Therapeutics, Inc.
B.1.3.4	Country	United States
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support
B.4.2	Country
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation
B.5.2	Functional name of contact point

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Chimeric natriuretic peptide - CDNP
D.3.2	Product code	CD-NP
D.3.4	Pharmaceutical form	Powder for solution for infusion
D.3.4.1	Specific paediatric formulation	Information not present in EudraCT
D.3.7	Routes of administration for this IMP	Intravenous drip use (Noncurrent)
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.2	Current sponsor code	CD-NP
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	1.0
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	Information not present in EudraCT
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	Information not present in EudraCT
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	Information not present in EudraCT
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Powder for solution for infusion
D.8.4	Route of administration of the placebo	Intravenous drip use (Noncurrent)

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Acute Decompensated Heart Failure

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	9.1
E.1.2	Level	LLT
E.1.2	Classification code	10064653
E.1.2	Term	Acute decompensated heart failure

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

To assess the safety and tolerability of CD-NP infusion

E.2.2

Secondary objectives of the trial

The secondary objectives of this study are to assess efficacy of CD-NP on improvement of clinical symptoms and major adverse cardiac and renal events, to explore dose relationship of CD-NP on biomarkers such as creatinine, Cystatin-C, NGAL, KIM1, and to explore relationship of CD-NP use to urine volume output, hospital readmission and medication intensification.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Be between 18 and 85 years of age, inclusive.
2. Systolic blood pressure ≥ 115 mmHg and ≤ 200 mmHg and diastolic blood pressure ≥ 60 mmHg and ≤ 110 mmHg at the time of screening.
3. Hospitalized for ADHF (decompensated chronic HF or acute HF). Patients who develop ADHF while hospitalized for another reason are not eligible.
4. The underlying primary etiology for ADHF should be cardiac rather than pulmonary disease. For this study, ADHF requires all of the following at the time of screening:
a. Dyspnea at rest (sitting or supine) or with minimal exertion (such as, talking, eating, etc.);
b. Pulmonary congestion on chest radiograph (X-ray) or on physical examination; and
c. BNP ≥ 300 pg/mL or NT-pro-BNP ≥ 1200 pg/mL.
5. Compromised renal function defined as CrCL from 30 to 89 mL/min (as estimated by either Cockcroft-Gault or Modification of Diet in Renal Disease (MDRD) Study
equations).
6. Able to begin study drug infusion within 24 hours from presentation to the hospital, including time spent in the emergency department.
7. Female patients must be post-menopausal or surgically sterile. A woman may be considered to be surgically sterilized if she has had a bilateral tubal ligation (for at least 6 months), bilateral oopherectomy or complete hysterectomy.
8. Be adequately informed of the nature and risks of the study and give written informed consent prior to receiving study medication.

The following criteria must continue to be met prior to study drug initiation:
1. Systolic blood pressure ≥ 115 mmHg and ≤ 200 mmHg and DBP ≥ 60 mmHg and ≤ 110 mmHg.
2. Has not received IV bolus dose of furosemide or equivalent loop diuretic including doses administered in the ambulance or emergency department, in excess of the following:
- 40 mg within 6 hours prior to study drug initiation
- 80 mg within 8 hours prior to study drug initiation
- 100 mg within 10 hours prior to study drug initiation
3. Has not received IV bolus dose of furosemide or equivalent loop diuretic within 2 hours prior to study drug initiation.
4. If receiving continuous IV infusion of diuretics or nitrates, the dose has not been up-titrated within 2 hours prior to dosing.
5. No morphine administration within 2 hours prior to dosing and able to withhold morphine administration for the first 6 hours after study drug initiation.

E.4

Principal exclusion criteria

1. Acute or suspected acute myocardial infarction (AMI) or troponin levels > 5X3X the upper limit of normal at the institution’s local laboratory.
2. Clinical diagnosis of acute coronary syndrome (ACS) within 30 days prior to screening.
3. Current or planned treatment with any of the following therapies prior to study drug initiation:
a. IV infusion of nesiritide, inotropic agents or vasopressors.
b. Received or planned to receive IV bolus dose(s) of furosemide or equivalent loop diuretic including doses administered in the ambulance or emergency
department, in excess of the following:
- 40 mg within 6 hours prior to study drug initiation
- 80 mg within 8 hours prior to study drug initiation
- 100 mg within 10 hours prior to study drug initiationin excess of 40 mg as a single dose
c. mechanical support (such as, intra-aortic balloon pumps, mechanical ventilation, or any ventricular assist device).
d. continuous positive positive airway pressure (CPAP).
e. intubation.
4. Cardiogenic shock.
5. Evidence of uncorrected volume depletion
6. Hyponatremia defined as serum Na ≤ 130 mEq/L.
7. Clinically significant aortic or mitral valve stenosis.
8. Temperature > 38°C (oral or equivalent), sepsis or active infection requiring IV anti-microbial treatment.
9. ADHF due to significant arrhythmias (ventricular tachycardia, bradyarrhythmias with ventricular rate < 45 beats per minute or atrial fibrillation/flutter with ventricular response of > 160 beats per minute).
10. Severe renal failure defined as creatinine clearance < 30 mL/min as estimated by
both the Cockcroft-Gault estimation and the MDRD equations
11. Current or planned ultrafiltration, hemofiltration, or dialysis.
12. Significant pulmonary disease (history of oral daily steroid dependency, history of CO2 retention or need for intubation for acute exacerbation, or currently receiving IV steroids).
13. Any organ transplant recipient, currently listed (anticipated in the next 60 days) for transplant, or admitted for cardiac transplantation.
14. Major surgery within 30 days.
15. Major neurologic event, including cerebrovascular events in the prior 60 days.
16. Acute myocarditis or hypertrophic obstructive, restrictive, or constrictive cardiomyopathy (not including restrictive mitral filling patterns).
17. Known hepatic impairment as indicated by any of the following:(total bilirubin > 3 mg/dL, albumin < 2.8 mg/dL, with other signs or symptoms of hepatic dysfunction or increased ammonia levels, if performed with other signs or symptoms of hepatic dysfunction ).
18. Received an investigational drug within 30 days prior to screening.
19. Women who are pregnant or breastfeeding.
20. Known hypersensitivity or allergy to natriuretic peptide or its components, nesiritide, other natriuretic peptides or related compounds.
21. Any condition which could interfere with, or for which the treatment might interfere with the conduct of the study, or which would unacceptably increase the risk of the patient's participation in the study. This may include, but is not limited to alcoholism, drug dependency or abuse, psychiatric disease, epilepsy, or any unexplained blackouts.
22. Patients diagnosed with Chagas’ cardiomyopathy.
23. Administration of IV contrast agent within the past 48 hours
24. Known predisposition to excessive vasodilatation in response to blood pressure lowering medications.

E.5 End points

E.5.1

Primary end point(s)

Key safety endpoints will include:
· The occurrence of symptomatic hypotension from start of study drug to within 6 hours after discontinuation of study drug
· The occurrence of either of the following from start of study drug to within 6 hours after discontinuation of study drug:
o a decrease in systolic blood pressure of at least 20 mm Hg to < 90 mmHg, or
o symptomatic hypotension.

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

Yes

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

Yes

E.8.2.3

Other

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

Information not present in EudraCT

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

E.8.7

Trial has a data monitoring committee

Yes

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

The end of the trial is defined by the last visit of the last subject, which occurs 30 to 33 days following the initiation of study drug infusion.

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.3

Elderly (>=65 years)

Yes

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

F.3.3.1

Women of childbearing potential not using contraception

Information not present in EudraCT

F.3.3.2

Women of child-bearing potential using contraception

Information not present in EudraCT

F.3.3.3

Pregnant women

Information not present in EudraCT

F.3.3.4

Nursing women

Information not present in EudraCT

F.3.3.5

Emergency situation

Information not present in EudraCT

F.3.3.6

Subjects incapable of giving consent personally

Information not present in EudraCT

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

F.4.2.2

In the whole clinical trial

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

Standard medical treatment

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2009-07-08

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2009-08-24

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2010-10-14

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