A randomized, double blind, placebo controlled, phase II, dose-titration trial to explore the safety, tolerability, pharmacokinetic profile and efficacy of M0002 in cirrhotic subjects with ascites and hypo- or normonatremia.
- Conditions
- Cirrhotic subjects with ascites and hypo- or normonatraemiaMedDRA version: 9.1Level: LLTClassification code 10009213Term: Cirrhosis of liverMedDRA version: 9.1Level: LLTClassification code 10003445Term: AscitesMedDRA version: 9.1Level: LLTClassification code 10021038Term: Hyponatremia
- Registration Number
- EUCTR2007-001711-31-DE
- Lead Sponsor
- Movetis NV
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 12
1.Male or female. Female subjects should be postmenopausal: prior oophorectomy, amenorrheic for 12 months or more in the absence of chemotherapy, tamoxifen, toremifene or ovarian suppression and follicle stimulating hormone and plasma estradiol in the postmenopausal range.
2.18 – 75 years of age inclusive.
3.Subjects with any form of cirrhosis with ascites on diuretic treatment and who had at least 1 paracentesis of at least 4 liter in the last 6 months.
4.The diagnosis of cirrhosis must be confirmed by clinical findings such as evidence of portal hypertension (prominent abdominal wall veins, oesophageal varices, hypersplenism) and / or abnormal laboratory tests (LFTs, coagulation disorders (prolonged coagulation time), low platelet count, anaemia, low albumin, low total protein. The presence of ascites must be documented by ultrasound imaging. Duration since diagnosis should be noted.
5.Dose of diuretics of spironolactone and furosemide should be stable for at least one week prior to the screening visit.
6.Subjects must have been on a salt restricted diet (< 5.2 grams sodium/day, 90 mmol) during the screening period prior to the trial drug administration.
7.Subjects (or their legally acceptable representatives) must have read and signed the written informed consent form after the nature of the trial has been fully explained, indicating the subject understands the purpose of and procedures required for the trial and is willing to comply with trial procedures and restrictions.
8.Other treatment for the management of cirrhosis and ascites should be stable for at least 2 weeks prior to trial drug administration.
9.Child-Pugh B and C (< 12) liver cirrhosis.
10.Subjects with hyponatraemia with sodium level between 120 and 132 mmol/L or normonatraemia with sodium level between 133 and 145 mmol/L measured at screening visit and day 1.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range
1.Women of child bearing potential (WOCBP).
2.Alcohol or drug abuse 4 weeks prior to screening and/or positive test at screening.
3.Malignancy.
4.Known renal impairment (serum creatinine > 2 mg/dL or 24-h creatinine clearance < 40 ml/min).
5.Recent infection (e.g. urinary tract infection, bacteremia, pneumonia, cellulitis) requiring treatment with antibiotics (e.g. ciprofloxacin, norfloxicin) within 14 days prior to trial entry. Long term, prophylactic antibiotic use is not excluded.
6.Surgery requiring general anesthesia within 30 days prior to trial entry.
7.Major pulmonary insufficiency.
8.Head trauma in the past 2 weeks.
9.Adrenal insufficiency, active encephalopathy grade II, uncontrolled hypo- or hyperthyroidism, unstable diabetes.
10.Subjects with spontaneous bacterial peritonitis (confirmed by culture) within 10 days prior to trial drug administration.
11.Gastrointestinal bleed within 10 days prior to trial drug administration.
12.Functional transjugular intrahepatic portasystemic stent shunt (TIPS), peritoneovenous shunt
13.Liver transplantation.
14.Budd-Chiari syndrome
15.Evidence of intravascular hypovolemia or major hemodynamic instability defined as systolic arterial pressure < 80 mm Hg, orthostatic hypotension, and pulse rate > 120 beats per minute.
16.Any evidence of active myocardial ischemia, myocardial infarction in the last 6 months.
17.Subjects with clinically relevant abnormal ECG intervals of morphology of the ECG, QTc > 480 ms.
18.Positive HIV test.
19.Hemoglobin < 9 g/dL.
20.Unstable hepatic disease (acute hepatitis, AST or ALT > 5 x upper limit of normal, bilirubin > 10 mg/dL)
21.Serum potassium > 6.0 mmol/L or < 3 mmol/L, osmolality > 295 mOs/kg.
22.Platelet count < 40 x 10³ / mm³.
23.Significant coagulopathy such as INR > 2.
24.Participation in an investigational drug or device trial within 30 days prior to screening.
25.Use of the following therapeutic agents: salt tablets or hypertonic saline, NSAIDs, corticosteroids, anticoagulants, saline solution, vasopressin analogs, DDAVP, lithium, demeclocycline, oncologic agents, drugs with potent CYP 3A4 inhibitors (such as itraconazole, ketoconazole, erythromycin, ritonavir, indinavir, sequinavir, …) or drugs known to affect platelet function within 14 days prior to trial drug administration.
26.Psychological and/or emotional problems, which would render the informed consent invalid, or limit the ability of the subjects to comply with the trial requirements.
27.Any condition that in the opinion of the investigator(s) would complicate or compromise the trial or the well being of the subject or evidence of clinically relevant pathology that could interfere with the trial results or put the subject’s safety at risk.
28. Signs of clinical dehydration
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To assess the safety and tolerability of M0002 after multiple oral dosing compared with placebo. ;Secondary Objective: To assess the efficacy of M0002 after multiple oral dosing compared with placebo. <br><br>To assess the pharmacokinetic behavior and relationship of the plasma drug concentration with the required effect of M0002 after multiple doses. <br>;Primary end point(s): To assess the safety and tolerability of M0002 after multiple oral dosing compared with placebo
- Secondary Outcome Measures
Name Time Method