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

Overt Hepatic Encephalopathy Clinical Trial

— OHE  

Official title:

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03515044
• Other study ID #: RNHE2041
• Status: Completed
• Phase: Phase 2
• Start date: September 13, 2018
• Est. completion date: March 12, 2020

Study information

• Verified date: March 2023
• Source: Bausch Health Americas, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 71
• Est. completion date: March 12, 2020
• Est. primary completion date: March 12, 2020
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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).

Related Conditions & MeSH terms

• Brain Diseases
• Hepatic Encephalopathy
• Overt Hepatic Encephalopathy

Intervention

Drug:
• 40 mg Rifaximin SSD once daily
SSD once daily (QD)
• 40 mg Rifaximin SSD twice daily
SSD twice daily (BID)
• 80 mg Rifaximin SSD once daily
SSD once daily (QD)
• 80 mg Rifaximin SSD twice daily
SSD twice daily (BID)
• Placebo
Administered twice daily (BID)

Locations

Country	Name	City	State
United States	Bausch Health Site 03	Boston	Massachusetts
United States	Bausch Health Site 13	Bristol	Connecticut
United States	Bausch Health Site 36	Brooklyn	New York
United States	Bausch Health Site 16	Charleston	South Carolina
United States	Bausch Health Site 05	Chicago	Illinois
United States	Bausch Health Site 17	Cincinnati	Ohio
United States	Bausch Health Site 23	Columbus	Ohio
United States	Bausch Health Site 18	Corona Del Mar	California
United States	Bausch Health Site 22	Dallas	Texas
United States	Bausch Health Site 31	Dallas	Texas
United States	Bausch Health Site 35	Dallas	Texas
United States	Bausch Health 01	Detroit	Michigan
United States	Bausch Health Site 07	Detroit	Michigan
United States	Bausch Health Site 02	Houston	Texas
United States	Bausch Health Site 37	Houston	Texas
United States	Bausch Health Site 33	Iowa City	Iowa
United States	Bausch Health Site 15	Los Angeles	California
United States	Bausch Health Site 19	Los Angeles	California
United States	Bausch Health Site 08	Miami	Florida
United States	Bausch Health Site 20	Milwaukee	Wisconsin
United States	Bausch Health Site 09	New York	New York
United States	Bausch Health Site 28	New York	New York
United States	Bausch Health Site 27	Newark	New Jersey
United States	Bausch Health Site 10	Philadelphia	Pennsylvania
United States	Bausch Health Site 11	Philadelphia	Pennsylvania
United States	Bausch Health Site 26	Philadelphia	Pennsylvania
United States	Bausch Health Site 12	Pittsburgh	Pennsylvania
United States	Bausch Health Site 06	Richmond	Virginia
United States	Bausch Health Site 30	Richmond	Virginia
United States	Bausch Health Site 24	Saint Louis	Missouri
United States	Bausch Health Site 04	San Francisco	California
United States	Bausch Health Site 14	Seattle	Washington
United States	Bausch Health Site 21	Seattle	Washington
United States	Bausch Health Site 25	Tupelo	Mississippi

Sponsors (1)

Lead Sponsor	Collaborator
Bausch Health Americas, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	Time to Hospital Discharge	Time in days until discharge from the hospital	14 days