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

Phase 2

Completed

• Conditions: Overt Hepatic Encephalopathy
• Interventions: Drug: 40 mg Rifaximin SSD twice daily; Drug: Placebo; Drug: 80 mg Rifaximin SSD once daily; Drug: 40 mg Rifaximin SSD once daily; Drug: 80 mg Rifaximin SSD twice daily

• Registration Number: NCT03515044
• Lead Sponsor: Bausch Health Americas, Inc.

Brief Summary

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

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 Timeline

• Study First Submitted: 2018-04-12
• Study First Submitted QC: 2018-05-02
• Study First Posted: 2018-05-03
• Study Start: 2018-09-13
• Primary Completion: 2020-03-12
• Study Completion: 2020-03-12
• Disposition First Submitted: 2021-03-10
• Results First Submitted: 2023-02-21
• Status Verified: 2023-03
• Results First Submitted QC: 2023-03-17
• Last Update Submitted: 2023-03-17
• Results First Posted: 2023-04-13
• Disposition First Posted: 2023-04-13
• Last Update Posted: 2023-04-13

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 71

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Cohort 2 40 mg Rifaximin SSD twice daily	40 mg Rifaximin SSD twice daily	40 mg Rifaximin immediate release (IR) rifaximin SSD twice daily (BID) and lactulose
Cohort 5 Placebo twice daily	Placebo	SSD placebo twice daily (BID) and lactulose
Cohort 3 80 mg Rifaximin SSD once daily	80 mg Rifaximin SSD once daily	80 mg Rifaximin sustained extended release (SER) rifaximin SSD once daily (QD) and lactulose
Cohort 1 40 mg Rifaximin SSD once daily	40 mg Rifaximin SSD once daily	40 mg Rifaximin immediate release (IR) rifaximin SSD once daily (QD) and lactulose
Cohort 4 80 mg Rifaximin SSD twice daiy	80 mg Rifaximin SSD twice daily	80 mg Rifaximin sustained extended release (SER) rifaximin SSD twice daily (BID) and lactulose

Primary Outcome Measures

Name	Time	Method
Time to Overt Hepatic Encephalopathy (OHE) Resolution Determined Using the Hepatic Encephalopathy Grading Instrument (HEGI), Defined as HEGI Score < 2	14 days	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).

Secondary Outcome Measures

Name	Time	Method
Time to Improvement in Hepatic Encephalopathy Grading Instrument (HEGI) Score, Defined as at Least One Grade Decrease (Improvement)	14 days	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).
Time to Hospital Discharge	14 days	Time in days until discharge from the hospital

Trial Locations

Locations (34)

Bausch Health Site 03; 🇺🇸 Boston, Massachusetts, United States

Bausch Health Site 08; 🇺🇸 Miami, Florida, United States

Bausch Health Site 16; 🇺🇸 Charleston, South Carolina, United States

Bausch Health Site 07; 🇺🇸 Detroit, Michigan, United States

Bausch Health Site 23; 🇺🇸 Columbus, Ohio, United States

Bausch Health Site 31; 🇺🇸 Dallas, Texas, United States

Bausch Health Site 18; 🇺🇸 Corona Del Mar, California, United States

Bausch Health Site 15; 🇺🇸 Los Angeles, California, United States

Bausch Health Site 19; 🇺🇸 Los Angeles, California, United States

Bausch Health Site 04; 🇺🇸 San Francisco, California, United States

Bausch Health Site 13; 🇺🇸 Bristol, Connecticut, United States

Bausch Health Site 05; 🇺🇸 Chicago, Illinois, United States

Bausch Health Site 33; 🇺🇸 Iowa City, Iowa, United States

Bausch Health 01; 🇺🇸 Detroit, Michigan, United States

Bausch Health Site 24; 🇺🇸 Saint Louis, Missouri, United States

Bausch Health Site 25; 🇺🇸 Tupelo, Mississippi, United States

Bausch Health Site 09; 🇺🇸 New York, New York, United States

Bausch Health Site 36; 🇺🇸 Brooklyn, New York, United States

Bausch Health Site 27; 🇺🇸 Newark, New Jersey, United States

Bausch Health Site 28; 🇺🇸 New York, New York, United States

Bausch Health Site 17; 🇺🇸 Cincinnati, Ohio, United States

Bausch Health Site 10; 🇺🇸 Philadelphia, Pennsylvania, United States

Bausch Health Site 26; 🇺🇸 Philadelphia, Pennsylvania, United States

Bausch Health Site 11; 🇺🇸 Philadelphia, Pennsylvania, United States

Bausch Health Site 12; 🇺🇸 Pittsburgh, Pennsylvania, United States

Bausch Health Site 22; 🇺🇸 Dallas, Texas, United States

Bausch Health Site 37; 🇺🇸 Houston, Texas, United States

Bausch Health Site 35; 🇺🇸 Dallas, Texas, United States

Bausch Health Site 30; 🇺🇸 Richmond, Virginia, United States

Bausch Health Site 02; 🇺🇸 Houston, Texas, United States

Bausch Health Site 21; 🇺🇸 Seattle, Washington, United States

Bausch Health Site 06; 🇺🇸 Richmond, Virginia, United States

Bausch Health Site 20; 🇺🇸 Milwaukee, Wisconsin, United States

Bausch Health Site 14; 🇺🇸 Seattle, Washington, United States