Clinical trial NCT03515044: Rifaximin Soluble Solid Dispersion (SSD) Tablets Plus Lactulose for the Treatment of Overt Hepatic Encephalopathy (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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Overt Hepatic Encephalopathy
Lead sponsor: Bausch Health Americas, Inc.
Sponsor class: INDUSTRY
First posted: 2018-05-03
Enrollment: 71
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized, Double-Blind, Placebo-Controlled, Dose-Ranging, Multicenter Study
Primary purpose: TREATMENT

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.

Eligibility criteria: 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).

Primary outcomes:
measure: Time to Overt Hepatic Encephalopathy (OHE) Resolution Determined Using the Hepatic Encephalopathy Grading Instrument (HEGI), Defined as HEGI Score < 2
timeFrame: 14 days
Secondary outcomes:
measure: Time to Improvement in Hepatic Encephalopathy Grading Instrument (HEGI) Score, Defined as at Least One Grade Decrease (Improvement)
timeFrame: 14 days
measure: Time to Hospital Discharge
timeFrame: 14 days
Other outcomes:
Locations:
city: Corona Del Mar
country: United States
facility: Bausch Health Site 18
state: California
city: Los Angeles
country: United States
facility: Bausch Health Site 15
state: California
city: Los Angeles
country: United States
facility: Bausch Health Site 19
state: California
city: San Francisco
country: United States
facility: Bausch Health Site 04
state: California
city: Bristol
country: United States
facility: Bausch Health Site 13
state: Connecticut
city: Miami
country: United States
facility: Bausch Health Site 08
state: Florida
city: Chicago
country: United States
facility: Bausch Health Site 05
state: Illinois
city: Iowa City
country: United States
facility: Bausch Health Site 33
state: Iowa
city: Boston
country: United States
facility: Bausch Health Site 03
state: Massachusetts
city: Detroit
country: United States
facility: Bausch Health Site 07
state: Michigan
city: Detroit
country: United States
facility: Bausch Health 01
state: Michigan
city: Tupelo
country: United States
facility: Bausch Health Site 25
state: Mississippi
city: Saint Louis
country: United States
facility: Bausch Health Site 24
state: Missouri
city: Newark
country: United States
facility: Bausch Health Site 27
state: New Jersey
city: Brooklyn
country: United States
facility: Bausch Health Site 36
state: New York
city: New York
country: United States
facility: Bausch Health Site 09
state: New York
city: New York
country: United States
facility: Bausch Health Site 28
state: New York
city: Cincinnati
country: United States
facility: Bausch Health Site 17
state: Ohio
city: Columbus
country: United States
facility: Bausch Health Site 23
state: Ohio
city: Philadelphia
country: United States
facility: Bausch Health Site 11
state: Pennsylvania
city: Philadelphia
country: United States
facility: Bausch Health Site 26
state: Pennsylvania
city: Philadelphia
country: United States
facility: Bausch Health Site 10
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Bausch Health Site 12
state: Pennsylvania
city: Charleston
country: United States
facility: Bausch Health Site 16
state: South Carolina
city: Dallas
country: United States
facility: Bausch Health Site 22
state: Texas
city: Dallas
country: United States
facility: Bausch Health Site 35
state: Texas
city: Dallas
country: United States
facility: Bausch Health Site 31
state: Texas
city: Houston
country: United States
facility: Bausch Health Site 02
state: Texas
city: Houston
country: United States
facility: Bausch Health Site 37
state: Texas
city: Richmond
country: United States
facility: Bausch Health Site 30
state: Virginia
city: Richmond
country: United States
facility: Bausch Health Site 06
state: Virginia
city: Seattle
country: United States
facility: Bausch Health Site 21
state: Washington
city: Seattle
country: United States
facility: Bausch Health Site 14
state: Washington
city: Milwaukee
country: United States
facility: Bausch Health Site 20
state: Wisconsin
Study officials:
affiliation: Bausch Health
name: Angela Bulawski
role: STUDY_DIRECTOR
References:
citation: Bajaj JS, Hassanein TI, Pyrsopoulos NT, Sanyal AJ, Rahimi RS, Heimanson Z, Israel RJ, Rockey DC. Dosing of Rifaximin Soluble Solid Dispersion Tablets in Adults With Cirrhosis: 2 Randomized, Placebo-controlled Trials. Clin Gastroenterol Hepatol. 2023 Mar;21(3):723-731.e9. doi: 10.1016/j.cgh.2022.05.042. Epub 2022 Jun 22.