E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Ascites complicating liver cirrhosis in males
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Ascites som komplikation til levercirros hos män |
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E.1.1.1 | Medical condition in easily understood language |
Fluid accumulation in the abdominal cavity due to cirrhosis of the liver in males |
Vätska i bukhålan hos manliga patienter med skrumplever |
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E.1.1.2 | Therapeutic area | Diseases [C] - Digestive System Diseases [C06] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10024667 |
E.1.2 | Term | Liver cirrhosis |
E.1.2 | System Organ Class | 100000004871 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10021038 |
E.1.2 | Term | Hyponatremia |
E.1.2 | System Organ Class | 100000004861 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10018800 |
E.1.2 | Term | Gynaecomastia |
E.1.2 | System Organ Class | 10038604 - Reproductive system and breast disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10003146 |
E.1.2 | Term | Arterial blood pressure decreased |
E.1.2 | System Organ Class | 100000004848 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10040409 |
E.1.2 | Term | Serum testosterone |
E.1.2 | System Organ Class | 100000004848 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 15.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10025522 |
E.1.2 | Term | Male sexual dysfunction NEC |
E.1.2 | System Organ Class | 10038604 - Reproductive system and breast disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10025503 |
E.1.2 | Term | Male erectile disorder |
E.1.2 | System Organ Class | 10038604 - Reproductive system and breast disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10064704 |
E.1.2 | Term | Decompensated cirrhosis |
E.1.2 | System Organ Class | 100000004871 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10023422 |
E.1.2 | Term | Kidney function abnormal |
E.1.2 | System Organ Class | 100000004857 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10020647 |
E.1.2 | Term | Hyperkalemia |
E.1.2 | System Organ Class | 100000004861 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10003445 |
E.1.2 | Term | Ascites |
E.1.2 | System Organ Class | 10017947 - Gastrointestinal disorders |
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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 |
To evaluate if therapy with eplerenone is non-inferior to spironolactone (both in combination with furosemide) regarding efficacy for mobilisation of ascites in male patients with cirrhosis of the liver. |
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E.2.2 | Secondary objectives of the trial |
To evaluate if therapy with eplerenone - in doses which control ascites - is superior to spironolactone (both in combination with furosemide) regarding antiandrogenic side effects (gynaecomastia, erectile dysfunction,reduced sexual arousal/desire, sex-related quality of life).
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. A written informed consent to participate in the study is signed before any study-related procedures are performed.
2. Male subject aged > 18 years and < 70 years
3. A definitive diagnosis of cirrhosis of the liver with clinically demonstrable ascites
4. A difference between plasma albumin concentration and ascites albumin concentration of > 10 g/liter
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E.4 | Principal exclusion criteria |
1. Therapy with spironolactone or eplerenone within 3 months prior to inclusion in the study (exception < 4 days of therapy with spironolactone immediately before inclusion in the study)
2. Prior/actual spontaneous bacterial peritonitis
3. Creatinine-clearance < 30 mL/min
4. Uncontrolled diabetes
5. Stroke within 6 months before inclusion in the study
6. Myocardial infarction within 6 months before inclusion in the study
7. Cardiac failure within 6 months before inclusion in the study
8. Known or suspected malignancies
9. Current therapy with drugs for erectile dysfunction
10. Current therapy with drugs for enlarged prostate
11. Current therapy with drugs interacting with spironolactone or eplerenone (Lithium, NSAID, ACE-inhibitors, AII-receptor blockers, trimethoprim, tricyclic antoidepressants, SSRI)
12. Current therapy with testosterone.
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E.5 End points |
E.5.1 | Primary end point(s) |
1. Absence of clinically detectable ascites.
2. Reduced clinical ascites with stable body weight +/- 1 kg from study week 12. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
1. Study week 24
2. Study week 24 |
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E.5.2 | Secondary end point(s) |
1. Absence or reduction of clinical ascites at week 12
2. Prevalence of refractory ascites at week 24 (defined according to international criteria – ref)
3. Alteration of breast tenderness > 1 degree from start of treatment to week 24
4. Alteration of gynaecomastia > 2 cm from start of treatment to week 24
5. Difference in score for sexual dysfunction from start of treatment to week 24
6. Difference in score for sexual dysfunction from start of treatment to week 24
7. Difference in score for sex-related QoL from start of treatment to week 24
8. Differences in serum hormoneconcentrations from start of treatment to week 24
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. Study week 12
2 - 8. Study week 24 |
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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 | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
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 | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
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) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
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.8.4.1 | Number of sites anticipated in Member State concerned | 7 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
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 | 2 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |