E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Hyponatremia in NYHA Class III/IV Cardiac Patient |
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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 | 10021036 |
E.1.2 | Term | Hyponatraemia |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main 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 in the full study cohort with patients with baseline in HF subjects with volume overload and hyponatremia (Baseline serum sodium ≥ 120 mEq/L to <130 mEq/L) |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives of this study are to determine whether: Administration of lixivaptan can effectively and safely produce an increase in serum sodium from in the full study cohort of subjects, baseline in HF subjects with volume overload and hyponatremia (Baseline serum sodium ≥ 120 mEq/L to <135 mEq/L). In subjects with Baseline serum sodium ≥ 120 mEq/L to <135 mEq/L, lixivaptan administration is associated with an improvement in clinical status as measured by days dead or hospitalized for cardiovascular causes within 60 days of randomization. Lixivaptan therapy demonstrates acute effects on body weight |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
1. The subject, or the subjects legally authorized representative, has provided written informed consent prior to initiation of any study-related procedures. 2. Male or female subject; females must be postmenopausal (at least 12 months since last menstrual period); surgically sterile (hysterectomy or tubal ligation at least 6 months prior to enrollment); using an intrauterine device; or a double barrier (e.g., diaphragm plus spermicide) non-hormonal contraceptive therapy for 2 weeks prior to Screening and agree to continue non-hormonal contraceptive therapy and must have a negative serum pregnancy test at the Screening visit. Abstinence is also an acceptable method of birth control. 3. The subject is 18 years of age or older. 4. The subject has either ischemic or non-ischemic cardiomyopathy (left ventricular dilatation and reduced systolic function) with a history of symptoms of New York Heart Association (NYHA) Class III or IV chronic heart failure (HF) (Appendix III). 5. The subject is currently hospitalized (from the time of screening) and has been hospitalized for no more than 3 days (72 hours). 6. The subject has at least a 3 month history of HF. The clinical diagnosis of HF must have been made at least 3 months prior to enrollment. A subject must have been hospitalized for HF within the previous 12 months. |
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E.4 | Principal exclusion criteria |
1. The subject was previously randomized to this study protocol. 2. If female, the subject is pregnant, breast feeding or using hormonal contraceptive therapy (injectable or topical contraceptives within 90 days of Screening or subcutaneous contraceptives within one year of Screening); or the subject is using oral hormonal contraceptive therapy during the 2 weeks prior to the Screening Visit. 3. The subject is unable to take oral medications. 4. The subject has severe hyponatremia (serum sodium < 120 mEq/L) or symptomatic hyponatremia (e.g., severe lethargy, coma, seizures, mental status changes attributable to hyponatremia). 5. The subject has uncontrolled diabetes mellitus (glucose ≥220 mg/dL). 6. The subject has acute pulmonary edema and is currently receiving any of the following: nitroprusside, nesiritide, intravenous nitroglycerine, IV inotrope or invasive hemodynamic monitoring with a pulmonary artery catheter |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy endpoint, time-normalized AUC for change from Baseline in serum sodium over the time course of 0 72 hours (nAUC0 72) (details for determination of nAUC0 72 are described in Section 7.10.1) will be calculated for the Modified Intent-to-Treat (MITT) subjects with Baseline serum sodium of <130 mEq/L |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Information not present in EudraCT |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | 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.8.5 | The trial involves multiple Member States | Yes |
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 |
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E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
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
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 9 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 9 |