Study of Efficacy of a Vasopressin 2 Receptor Antagonist M0002 for Treatment of Ascites in Cirrhotic Subjects With Hypo- or Normonatraemia

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 Normonatraemia.

M0002, an orally active, selective non-peptidergic antagonist of the vasopressin V2 receptor inhibits vasopressin-induced water reabsorption from the kidney. Therefore the aquaretic effect of M0002 has a potential clinical benefit in the treatment of ascites and hyponatreamia in cirrhotic patients.

Study Overview

• Status: Completed
• Conditions: Cirrhotic Ascites
• Intervention / Treatment: Drug: Placebo; Drug: M0002

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Main Inclusion Criteria:

1. Subjects with any form of cirrhosis with ascites and who had at least 1 paracentesis of at least 4 liter in the last 6 months.
2. Dose of diuretics of spironolactone and furosemide was to be stable for at least one week prior to the screening visit or subject was refractory to diuretics.
3. Subjects had to have been on a salt restricted diet (< 5.2 grams sodium/day, 90 mmol) during the screening period prior to the trial drug administration.
4. Other treatment for the management of cirrhosis and ascites should be stable for at least 2 weeks prior to trial drug administration.
5. Child-Pugh B and C liver cirrhosis score lower than 12.
6. 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.

Main Exclusion Criteria:

1. Women of child bearing potential (WOCBP)
2. Functional transjugular intrahepatic portasystemic stent shunt (TIPS), peritoneovenous shunt
3. Liver transplantation
4. Budd-Chiari syndrome
5. Unstable hepatic disease (acute hepatitis, AST or ALT > 5 x upper limit of normal, bilirubin > 10 mg/dL)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Placebo	Drug: Placebo
ACTIVE_COMPARATOR: M0002; Started at 0.3 mg/day and increased every 3 days (to 1, 3 and 6 mg/day); for hyponatraemic subjects: dose was increased until the evening serum level was between 132 mmol/l and 145 mmol/l;; for normonatraemic subjects the dose was increased until a 500 ml increase in the 24-h urine volume compared with Day-1 was reached. Once the required response or max dose was achieved, subjects entered a maintenance phase where they remained on the same dose of M0002 or placebo until 15 days.	Drug: M0002

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Plasma sodium levels, weight, number of paracentesis	15 days

Collaborators and Investigators

• Sponsor: Movetis

Study record dates

Study Major Dates

• Study Start: June 1, 2007
• Primary Completion (ACTUAL): December 1, 2007
• Study Completion (ACTUAL): December 1, 2007

Study Registration Dates

• First Submitted: August 10, 2010
• First Submitted That Met QC Criteria: August 10, 2010
• First Posted (ESTIMATE): August 11, 2010

Study Record Updates

• Last Update Posted (ESTIMATE): August 11, 2010
• Last Update Submitted That Met QC Criteria: August 10, 2010
• Last Verified: July 1, 2010

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Ascites
• Other Study ID Numbers: M0002-BEL-C201