Rifaximin Soluble Solid Dispersion (SSD) Tablets Plus Lactulose for the Treatment of Overt Hepatic Encephalopathy (OHE) (OHE)

A Randomized, Double-Blind, Placebo-Controlled, Dose-Ranging, Multicenter Study to Assess the Efficacy and Safety of Rifaximin Soluble Solid Dispersion (SSD) Tablets Plus Lactulose for the Treatment of Overt Hepatic Encephalopathy (OHE)

Study to Assess the Efficacy and Safety of Rifaximin Soluble Solid Dispersion (SSD) Tablets Plus Lactulose for the Treatment of Overt Hepatic Encephalopathy (OHE).

Study Overview

• Status: Completed
• Conditions: Overt Hepatic Encephalopathy
• Intervention / Treatment: Drug: 40 mg Rifaximin SSD once daily; Drug: 40 mg Rifaximin SSD twice daily; Drug: 80 mg Rifaximin SSD once daily; Drug: 80 mg Rifaximin SSD twice daily; Drug: Placebo

Detailed Description

The primary objective of this study is to assess the efficacy of rifaximin SSD plus lactulose versus placebo plus lactulose for the treatment of overt hepatic encephalopathy (OHE). The secondary objectives of this study are to assess the safety of rifaximin SSD in subjects with OHE and to assess the effects of treatment with rifaximin SSD on key secondary endpoints.

• Study Type: Interventional
• Enrollment (Actual): 71
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Corona Del Mar, California, United States, 92118
      • Bausch Health Site 18
    • Los Angeles, California, United States, 90033
      • Bausch Health Site 15
    • Los Angeles, California, United States, 90048
      • Bausch Health Site 19
    • San Francisco, California, United States, 94143
      • Bausch Health Site 04
  • Connecticut
    • Bristol, Connecticut, United States, 06010
      • Bausch Health Site 13
  • Florida
    • Miami, Florida, United States, 33136
      • Bausch Health Site 08
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Bausch Health Site 05
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • Bausch Health Site 33
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Bausch Health Site 03
  • Michigan
    • Detroit, Michigan, United States, 48109
      • Bausch Health Site 07
    • Detroit, Michigan, United States, 48127
      • Bausch Health 01
  • Mississippi
    • Tupelo, Mississippi, United States, 38801
      • Bausch Health Site 25
  • Missouri
    • Saint Louis, Missouri, United States, 63104
      • Bausch Health Site 24
  • New Jersey
    • Newark, New Jersey, United States, 07102
      • Bausch Health Site 27
  • New York
    • Brooklyn, New York, United States, 11215
      • Bausch Health Site 36
    • New York, New York, United States, 10029
      • Bausch Health Site 09
    • New York, New York, United States, 10065
      • Bausch Health Site 28
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • Bausch Health Site 17
    • Columbus, Ohio, United States, 43210
      • Bausch Health Site 23
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Bausch Health Site 11
    • Philadelphia, Pennsylvania, United States, 19107
      • Bausch Health Site 26
    • Philadelphia, Pennsylvania, United States, 19141
      • Bausch Health Site 10
    • Pittsburgh, Pennsylvania, United States, 15213
      • Bausch Health Site 12
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Bausch Health Site 16
  • Texas
    • Dallas, Texas, United States, 75203
      • Bausch Health Site 22
    • Dallas, Texas, United States, 75246
      • Bausch Health Site 35
    • Dallas, Texas, United States, 75390
      • Bausch Health Site 31
    • Houston, Texas, United States, 77001
      • Bausch Health Site 02
    • Houston, Texas, United States, 77030
      • Bausch Health Site 37
  • Virginia
    • Richmond, Virginia, United States, 23226
      • Bausch Health Site 30
    • Richmond, Virginia, United States, 23249
      • Bausch Health Site 06
  • Washington
    • Seattle, Washington, United States, 98104
      • Bausch Health Site 21
    • Seattle, Washington, United States, 98195
      • Bausch Health Site 14
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Bausch Health Site 20

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Male or female age 18 to 75 years of age (inclusive) at the time of screening.
• Females of childbearing potential, defined as a female who is fertile following menarche, must have a negative serum pregnancy test at screening and agree to use an acceptable method of contraception throughout their participation in the study.

Note: Female subjects who have been surgically sterilized (e.g., hysterectomy or bilateral tubal ligation) or who are postmenopausal (defined as total cessation of menses for > 1 year) will not be considered "female subjects of childbearing potential".

• Subject is hospitalized with liver cirrhosis and/or OHE and has a confirmed diagnosis of OHE at Baseline.
• Subject has a Grade 2 or Grade 3 HE episode according to the HE Grading Instrument (HEGI) following 8 to 12 hours of intravenous (IV) hydration and lactulose treatment.

Exclusion Criteria:

• Subject has an uncontrolled major psychiatric disorder including major depression or psychoses as determined by the investigator.
• Subject has been diagnosed with an infection for which they are currently taking oral or parenteral antibiotics, which cannot be discontinued at time of enrollment. Note: Subjects currently taking Rifaximin are not excluded
• Subject shows presence of intestinal obstruction or has inflammatory bowel disease.
• Subject has uncontrolled Type 1 or Type 2 diabetes. Note: Subjects with controlled diabetes may be enrolled if they are on stable doses of oral hypoglycemic drugs for at least 3 months prior to screening, and demonstrate clinically acceptable blood glucose control at Baseline, as determined by the investigator.
• Subject has an active malignancy (exceptions: non-melanoma skin cancers).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1 40 mg Rifaximin SSD once daily; 40 mg Rifaximin immediate release (IR) rifaximin SSD once daily (QD) and lactulose	Drug: 40 mg Rifaximin SSD once daily; SSD once daily (QD)
Experimental: Cohort 2 40 mg Rifaximin SSD twice daily; 40 mg Rifaximin immediate release (IR) rifaximin SSD twice daily (BID) and lactulose	Drug: 40 mg Rifaximin SSD twice daily; SSD twice daily (BID)
Experimental: Cohort 3 80 mg Rifaximin SSD once daily; 80 mg Rifaximin sustained extended release (SER) rifaximin SSD once daily (QD) and lactulose	Drug: 80 mg Rifaximin SSD once daily; SSD once daily (QD)
Experimental: Cohort 4 80 mg Rifaximin SSD twice daiy; 80 mg Rifaximin sustained extended release (SER) rifaximin SSD twice daily (BID) and lactulose	Drug: 80 mg Rifaximin SSD twice daily; SSD twice daily (BID)
Experimental: Cohort 5 Placebo twice daily; SSD placebo twice daily (BID) and lactulose	Drug: Placebo; Administered twice daily (BID)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Overt Hepatic Encephalopathy (OHE) Resolution Determined Using the Hepatic Encephalopathy Grading Instrument (HEGI), Defined as HEGI Score < 2	A participant was considered to have an overt HE episode if at least one of the following applied: (1) Disorientated to time or place or person, (2) Lethargic and has asterixis, (3) Inability to assess the patient due to disorientation to time and place and person; and/or somnolence, and/or coma. Severity of OHE episodes was graded using the HEGI scale, where Grade 1 is no clinical findings of OHE, and Grade 4 is comatose. Higher scores on the scale have higher severity (worse outcome).	14 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Improvement in Hepatic Encephalopathy Grading Instrument (HEGI) Score, Defined as at Least One Grade Decrease (Improvement)	A participant was considered to have an overt HE episode if at least one of the following applied: (1) Disorientated to time or place or person, (2) Lethargic and has asterixis, (3) Inability to assess the patient due to disorientation to time and place and person; and/or somnolence, and/or coma. Severity of OHE episodes was graded using the HEGI scale, where Grade 1 is no clinical findings of OHE, and Grade 4 is comatose. Higher scores on the scale have higher severity (worse outcome).	14 days
Time to Hospital Discharge	Time in days until discharge from the hospital	14 days

Collaborators and Investigators

• Sponsor: Bausch Health Americas, Inc.

Publications and helpful links

General Publications

• Streng BMM, Bont M, Delemarre EM, Binnendijk RS, Smit G, den Hartog G, Coppus AMW, de Vries E, Weijerman ME, Lamberts R, de Graaf G, van der Klis FR, Vidarsson G, Rave N, Bont LJ, Wildenbeest JG. Decreased Antibody Response After Severe Acute Respiratory Syndrome Coronavirus 2 Vaccination in Patients With Down Syndrome. J Infect Dis. 2022 Sep 4;226(4):673-677. doi: 10.1093/infdis/jiac235.

Study record dates

Study Major Dates

• Study Start (Actual): September 13, 2018
• Primary Completion (Actual): March 12, 2020
• Study Completion (Actual): March 12, 2020

Study Registration Dates

• First Submitted: April 12, 2018
• First Submitted That Met QC Criteria: May 2, 2018
• First Posted (Actual): May 3, 2018

Study Record Updates

• Last Update Posted (Actual): April 13, 2023
• Last Update Submitted That Met QC Criteria: March 17, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Failure; Hepatic Insufficiency; Metabolic Diseases; Central Nervous System Diseases; Nervous System Diseases; Liver Diseases; Brain Diseases, Metabolic; Hepatic Encephalopathy; Brain Diseases; Anti-Infective Agents; Gastrointestinal Agents; Anti-Bacterial Agents; Rifaximin
• Other Study ID Numbers: RNHE2041

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No