Kliiniset tutkimukset Nct sivu

Summary
EudraCT Number:2006-002567-62
Sponsor's Protocol Code Number:CK-LX3401
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:2007-12-06
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
A. Protocol Information
A.1Member State ConcernedGermany - BfArM
A.2EudraCT number2006-002567-62
A.3Full title of the trial
THE BALANCE Study: Treatment of Hyponatremia Based on Lixivaptan in NYHA Class III/IV Cardiac Patient Evaluation
A.4.1Sponsor's protocol code numberCK-LX3401
A.7Trial is part of a Paediatric Investigation Plan Information not present in EudraCT
A.8EMA Decision number of Paediatric Investigation Plan
B. Sponsor Information
B.Sponsor: 1
B.1.1Name of SponsorCardiokine Biopharma, LLC
B.1.3.4CountryUnited States
B.3.1 and B.3.2Status of the sponsorCommercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1Name of organisation providing support
B.4.2Country
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1Name of organisation
B.5.2Functional name of contact point
D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3IMP RoleTest
D.2 Status of the IMP to be used in the clinical trial
D.2.1IMP to be used in the trial has a marketing authorisation No
D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
D.2.5.1Orphan drug designation number
D.3 Description of the IMP
D.3.1Product nameLixivaptan
D.3.4Pharmaceutical form Capsule, hard
D.3.4.1Specific paediatric formulation Information not present in EudraCT
D.3.7Routes of administration for this IMPOral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8INN - Proposed INNLixivaptan
D.3.9.1CAS number 168079-32-1
D.3.9.2Current sponsor codeVPA-985
D.3.10 Strength
D.3.10.1Concentration unit mg milligram(s)
D.3.10.2Concentration typeequal
D.3.10.3Concentration number25
D.3.11 The IMP contains an:
D.3.11.1Active substance of chemical origin Yes
D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
The IMP is a:
D.3.11.3Advanced Therapy IMP (ATIMP) Information not present in EudraCT
D.3.11.3.1Somatic cell therapy medicinal product No
D.3.11.3.2Gene therapy medical product No
D.3.11.3.3Tissue Engineered Product Information not present in EudraCT
D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) Information not present in EudraCT
D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy Information not present in EudraCT
D.3.11.5Radiopharmaceutical medicinal product No
D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
D.3.11.7Plasma derived medicinal product No
D.3.11.8Extractive medicinal product No
D.3.11.9Recombinant medicinal product Information not present in EudraCT
D.3.11.10Medicinal product containing genetically modified organisms No
D.3.11.11Herbal medicinal product No
D.3.11.12Homeopathic medicinal product No
D.3.11.13Another type of medicinal product No
D.IMP: 2
D.1.2 and D.1.3IMP RoleTest
D.2 Status of the IMP to be used in the clinical trial
D.2.1IMP to be used in the trial has a marketing authorisation No
D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
D.2.5.1Orphan drug designation number
D.3 Description of the IMP
D.3.1Product nameLixivaptan
D.3.4Pharmaceutical form Capsule, hard
D.3.4.1Specific paediatric formulation Information not present in EudraCT
D.3.7Routes of administration for this IMPOral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8INN - Proposed INNLixivaptan
D.3.9.1CAS number 168079-32-1
D.3.9.2Current sponsor codeVPA-985
D.3.10 Strength
D.3.10.1Concentration unit mg milligram(s)
D.3.10.2Concentration typeequal
D.3.10.3Concentration number50
D.3.11 The IMP contains an:
D.3.11.1Active substance of chemical origin Yes
D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
The IMP is a:
D.3.11.3Advanced Therapy IMP (ATIMP) Information not present in EudraCT
D.3.11.3.1Somatic cell therapy medicinal product No
D.3.11.3.2Gene therapy medical product No
D.3.11.3.3Tissue Engineered Product Information not present in EudraCT
D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) Information not present in EudraCT
D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy Information not present in EudraCT
D.3.11.5Radiopharmaceutical medicinal product No
D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
D.3.11.7Plasma derived medicinal product No
D.3.11.8Extractive medicinal product No
D.3.11.9Recombinant medicinal product Information not present in EudraCT
D.3.11.10Medicinal product containing genetically modified organisms No
D.3.11.11Herbal medicinal product No
D.3.11.12Homeopathic medicinal product No
D.3.11.13Another type of medicinal product No
D.8 Information on Placebo
D.8 Placebo: 1
D.8.1Is a Placebo used in this Trial?Yes
D.8.3Pharmaceutical form of the placeboCapsule, hard
D.8.4Route of administration of the placeboOral use
D.8 Placebo: 2
D.8.1Is a Placebo used in this Trial?Yes
D.8.3Pharmaceutical form of the placeboCapsule, hard
D.8.4Route of administration of the placeboOral use
E. General Information on the Trial
E.1 Medical condition or disease under investigation
E.1.1Medical condition(s) being investigated
Hyponatremia
MedDRA Classification
E.1.2 Medical condition or disease under investigation
E.1.2Version 9.1
E.1.2Level LLT
E.1.2Classification code 10021038
E.1.2Term Hyponatremia
E.1.3Condition being studied is a rare disease No
E.2 Objective of the trial
E.2.1Main objective of the trial
The primary objective of this study is to determine whether administration of lixivaptan can effectively and safely produce an increase in serum sodium from Baseline in HF patients with volume overload and hyponatremia.
E.2.2Secondary objectives of the trial
The secondary objectives of this study are that lixivaptan:
a. Demonstrates improvement in serum sodium concentrations (AUC) up to Day 60 within the double-blind on-therapy period for hyponatremic patients with serum sodium <135 mEq/L at Baseline.
b. Is associated with improvement in clinical status as measured by:
i. Changes in the Trail Making Test, part B following 28 days of dosing.
ii. Days alive and out of the hospital (for cardiovascular causes) within 60-Days of randomisation.
c. Prevents worsening of hyponatremia
d. Improves the percentage of patients with normalized serum sodium.
E.2.3Trial contains a sub-study Yes
E.2.3.1Full title, date and version of each sub-study and their related objectives
Pharmacoeconomic Study - US only. Full details and study objectives of the sub-study are contained in the protocol.
E.3Principal inclusion criteria
1. Men and Women with age greater than or equal to 18 years.
2. Baseline Serum sodium concentration < 135 mEq/L. Repeat measures of serum sodium are alllowed; the last serum sodium result within 24 hours prior to randomization will serve as the qualifying measurement.
3. Current hospitalization for worsening of chronic congestive heart failure.
a) Chronic heart failure is defined as requiring treatment for a minimum of 30-Days prior to hospitalization. Study patients are expected to be on standard background therapy for Congestive Heart Failure.
4. The patient has clinical evidence of volume overload with at least two of the following:
a) dyspnea,
b) pulmonary congestion (rales),
c) peripheral edema,
d) increased jugular venous pressure and/or hepatic congestion with ascites,
e) chest x-ray consistent with CHF, or
f) plasma BNP ≥ 150 pg/mL or NT pro-BNP ≥ 450 pg/mL.
5. The patient has documented Left Ventricular Ejection Fraction (LVEF) within the past year.
6. Supine systolic arterial blood pressure ≥ 90 mmHg.
E.4Principal exclusion criteria
1. Previous participation in this or any other lixivaptan clinical trial.
2. Participation in any other investigational study of drugs or devices within 30-Days prior to Screening.
3. Women who will not adhere to the reproductive precautions as outlined in section 4.3 of the protocol and in the informed consent form.
4. Positive urine pregnancy test.
5. Inability to provide informed consent.
6. Inability to respond to thirst.
7. Inability to take oral medications.
8. Acute severe hyponatremia.
9. Overt symptoms of hyponatremia requiring immediate medical intervention (e.g., severe lethargy, coma, seizures).
10. Hemodynamically significant uncorrected primary cardiac valvular disease.
11. Hypertrophic cardiomyopathy (obstructive or non-obstructive).
12. CHF due to uncorrected thyroid disease (i.e., T4 above or below the limits of the reference range), active myocarditis or known amyloid cardiomyopathy.
13. History of sustained ventricular tachycardia or ventricular fibrillation within 30 days, unless in the presence of an automatic implantable cardioverter defibrillator.
14. ST-segment elevation myocardial infarction (STEMI) within 30-Days or active myocardial ischemia at the time of enrollment.
15. History of stroke within 30-Days prior to screening.
16. History of a cardiac revascularization procedure within 30-Days prior to screening.
17. Subjects who are on cardiac mechanical support.
18. History of bi-ventricular pacer placement within the last 30-Days.
19. Planned revascularization procedures, electrophysiologic (EP) device implantation, cardiac mechanical support implantation, ultrafiltration or dialysis, or other cardiac surgery within 30 days following study enrollment.
20. Serum creatinine > 3.0 mg/dL/265.2 mol/L.
21. Uncontrolled diabetes mellitus as defined by the Investigator (e.g. HbA1c > 9%).
22. Adrenal insufficiency, whether treated or not. If serum cortisol is less than the lower limit of the reference range, the patient is excluded and should be referred for follow-up evaluation.
23. History of primary significant liver disease or acute hepatic failure, as defined by the Investigator.
24. History of chronic drug/medication abuse within the 6 months, or current alcohol abuse.
25. Co-morbid condition with an expected survival less than six months.

Specific requirements for females
Women of child-bearing potential must demonstrate a negative urine pregnancy test prior to randomization and at the final study visit 30 days after the last dose of study drug. In addition, women of child-bearing potential must agree to use one of the methods of birth control detailed in 4.3 of the protocol for the entire study period including screening, the titration and treatment phases and the 30-day follow-up period.
E.5 End points
E.5.1Primary end point(s)
The change from baseline in serum sodium concentrations at day 7 of the double-blind on-therapy period for hyponatremic patients with serum sodium of <135 mEq/L at baseline.
E.6 and E.7 Scope of the trial
E.6Scope of the trial
E.6.1Diagnosis No
E.6.2Prophylaxis No
E.6.3Therapy Yes
E.6.4Safety Yes
E.6.5Efficacy Yes
E.6.6Pharmacokinetic Yes
E.6.7Pharmacodynamic Yes
E.6.8Bioequivalence No
E.6.9Dose response No
E.6.10Pharmacogenetic No
E.6.11Pharmacogenomic No
E.6.12Pharmacoeconomic No
E.6.13Others No
E.7Trial type and phase
E.7.1Human pharmacology (Phase I) No
E.7.1.1First administration to humans Information not present in EudraCT
E.7.1.2Bioequivalence study Information not present in EudraCT
E.7.1.3Other Information not present in EudraCT
E.7.1.3.1Other trial type description
E.7.2Therapeutic exploratory (Phase II) No
E.7.3Therapeutic confirmatory (Phase III) Yes
E.7.4Therapeutic use (Phase IV) No
E.8 Design of the trial
E.8.1Controlled Yes
E.8.1.1Randomised Yes
E.8.1.2Open No
E.8.1.3Single blind No
E.8.1.4Double blind Yes
E.8.1.5Parallel group Yes
E.8.1.6Cross over No
E.8.1.7Other No
E.8.2 Comparator of controlled trial
E.8.2.1Other medicinal product(s) No
E.8.2.2Placebo Yes
E.8.2.3Other No
E.8.3 The trial involves single site in the Member State concerned No
E.8.4 The trial involves multiple sites in the Member State concerned Yes
E.8.4.1Number of sites anticipated in Member State concerned25
E.8.5The trial involves multiple Member States Yes
E.8.5.1Number of sites anticipated in the EEA100
E.8.6 Trial involving sites outside the EEA
E.8.6.1Trial being conducted both within and outside the EEA Yes
E.8.6.2Trial being conducted completely outside of the EEA Information not present in EudraCT
E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
E.8.7Trial 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
E.8.9 Initial estimate of the duration of the trial
E.8.9.1In the Member State concerned years2
E.8.9.1In the Member State concerned months0
E.8.9.1In the Member State concerned days0
E.8.9.2In all countries concerned by the trial years2
E.8.9.2In all countries concerned by the trial months0
E.8.9.2In all countries concerned by the trial days0
F. Population of Trial Subjects
F.1 Age Range
F.1.1Trial has subjects under 18 No
F.1.1.1In Utero Information not present in EudraCT
F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) Information not present in EudraCT
F.1.1.3Newborns (0-27 days) Information not present in EudraCT
F.1.1.4Infants and toddlers (28 days-23 months) Information not present in EudraCT
F.1.1.5Children (2-11years) Information not present in EudraCT
F.1.1.6Adolescents (12-17 years) Information not present in EudraCT
F.1.2Adults (18-64 years) Yes
F.1.3Elderly (>=65 years) Yes
F.2 Gender
F.2.1Female Yes
F.2.2Male Yes
F.3 Group of trial subjects
F.3.1Healthy volunteers No
F.3.2Patients Yes
F.3.3Specific vulnerable populations Yes
F.3.3.1Women of childbearing potential not using contraception For clinical trials recorded in the database before the 10th March 2011 this question read: "Women of childbearing potential" and did not include the words "not using contraception". An answer of yes could have included women of child bearing potential whether or not they would be using contraception. The answer should therefore be understood in that context. This trial was recorded in the database on 2007-12-06. Yes
F.3.3.2Women of child-bearing potential using contraception Yes
F.3.3.3Pregnant women No
F.3.3.4Nursing women No
F.3.3.5Emergency situation No
F.3.3.6Subjects incapable of giving consent personally No
F.3.3.7Others No
F.4 Planned number of subjects to be included
F.4.1In the member state100
F.4.2 For a multinational trial
F.4.2.1In the EEA 325
F.4.2.2In the whole clinical trial 650
G. Investigator Networks to be involved in the Trial
N. Review by the Competent Authority or Ethics Committee in the country concerned
N.Competent Authority Decision Authorised
N.Date of Competent Authority Decision2008-03-04
N.Ethics Committee Opinion of the trial applicationFavourable
N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
N.Date of Ethics Committee Opinion
P. End of Trial
P.End of Trial StatusCompleted
P.Date of the global end of the trial2010-06-17

Sponsorit ja yhteistyökumppanit

Sairaudet

Huumeiden interventiot

3
Tilaa