NCT03515044

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).

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
71

participants targeted

Target at P50-P75 for phase_2

Timeline
Completed

Started Sep 2018

Shorter than P25 for phase_2

Geographic Reach
1 country

34 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

April 12, 2018

Completed
21 days until next milestone

First Posted

Study publicly available on registry

May 3, 2018

Completed
4 months until next milestone

Study Start

First participant enrolled

September 13, 2018

Completed
1.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 12, 2020

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

March 12, 2020

Completed
3.1 years until next milestone

Results Posted

Study results publicly available

April 13, 2023

Completed
Last Updated

April 13, 2023

Status Verified

March 1, 2023

Enrollment Period

1.5 years

First QC Date

April 12, 2018

Results QC Date

February 21, 2023

Last Update Submit

March 17, 2023

Conditions

Overt Hepatic Encephalopathy

Outcome Measures

Primary Outcomes (1)

  • 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 Outcomes (2)

  • Time to Improvement in Hepatic Encephalopathy Grading Instrument (HEGI) Score, Defined as at Least One Grade Decrease (Improvement)

    14 days

  • Time to Hospital Discharge

    14 days

Study Arms (5)

Cohort 1 40 mg Rifaximin SSD once daily

EXPERIMENTAL

40 mg Rifaximin immediate release (IR) rifaximin SSD once daily (QD) and lactulose

Drug: 40 mg Rifaximin SSD once daily

Cohort 2 40 mg Rifaximin SSD twice daily

EXPERIMENTAL

40 mg Rifaximin immediate release (IR) rifaximin SSD twice daily (BID) and lactulose

Drug: 40 mg Rifaximin SSD twice daily

Cohort 3 80 mg Rifaximin SSD once daily

EXPERIMENTAL

80 mg Rifaximin sustained extended release (SER) rifaximin SSD once daily (QD) and lactulose

Drug: 80 mg Rifaximin SSD once daily

Cohort 4 80 mg Rifaximin SSD twice daiy

EXPERIMENTAL

80 mg Rifaximin sustained extended release (SER) rifaximin SSD twice daily (BID) and lactulose

Drug: 80 mg Rifaximin SSD twice daily

Cohort 5 Placebo twice daily

EXPERIMENTAL

SSD placebo twice daily (BID) and lactulose

Drug: Placebo

Interventions

40 mg Rifaximin SSD once dailyDRUG

SSD once daily (QD)

Cohort 1 40 mg Rifaximin SSD once daily
40 mg Rifaximin SSD twice dailyDRUG

SSD twice daily (BID)

Cohort 2 40 mg Rifaximin SSD twice daily
80 mg Rifaximin SSD once dailyDRUG

SSD once daily (QD)

Cohort 3 80 mg Rifaximin SSD once daily
80 mg Rifaximin SSD twice dailyDRUG

SSD twice daily (BID)

Cohort 4 80 mg Rifaximin SSD twice daiy
PlaceboDRUG

Administered twice daily (BID)

Cohort 5 Placebo twice daily

Eligibility Criteria

Age18 Years - 75 Years
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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.

You may not qualify if:

  • 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).

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (34)

Bausch Health Site 18

Corona del Mar, California, 92118, United States

Location

Bausch Health Site 15

Los Angeles, California, 90033, United States

Location

Bausch Health Site 19

Los Angeles, California, 90048, United States

Location

Bausch Health Site 04

San Francisco, California, 94143, United States

Location

Bausch Health Site 13

Bristol, Connecticut, 06010, United States

Location

Bausch Health Site 08

Miami, Florida, 33136, United States

Location

Bausch Health Site 05

Chicago, Illinois, 60611, United States

Location

Bausch Health Site 33

Iowa City, Iowa, 52242, United States

Location

Bausch Health Site 03

Boston, Massachusetts, 02215, United States

Location

Bausch Health Site 07

Detroit, Michigan, 48109, United States

Location

Bausch Health 01

Detroit, Michigan, 48127, United States

Location

Bausch Health Site 25

Tupelo, Mississippi, 38801, United States

Location

Bausch Health Site 24

St Louis, Missouri, 63104, United States

Location

Bausch Health Site 27

Newark, New Jersey, 07102, United States

Location

Bausch Health Site 36

Brooklyn, New York, 11215, United States

Location

Bausch Health Site 09

New York, New York, 10029, United States

Location

Bausch Health Site 28

New York, New York, 10065, United States

Location

Bausch Health Site 17

Cincinnati, Ohio, 45219, United States

Location

Bausch Health Site 23

Columbus, Ohio, 43210, United States

Location

Bausch Health Site 11

Philadelphia, Pennsylvania, 19104, United States

Location

Bausch Health Site 26

Philadelphia, Pennsylvania, 19107, United States

Location

Bausch Health Site 10

Philadelphia, Pennsylvania, 19141, United States

Location

Bausch Health Site 12

Pittsburgh, Pennsylvania, 15213, United States

Location

Bausch Health Site 16

Charleston, South Carolina, 29425, United States

Location

Bausch Health Site 22

Dallas, Texas, 75203, United States

Location

Bausch Health Site 35

Dallas, Texas, 75246, United States

Location

Bausch Health Site 31

Dallas, Texas, 75390, United States

Location

Bausch Health Site 02

Houston, Texas, 77001, United States

Location

Bausch Health Site 37

Houston, Texas, 77030, United States

Location

Bausch Health Site 30

Richmond, Virginia, 23226, United States

Location

Bausch Health Site 06

Richmond, Virginia, 23249, United States

Location

Bausch Health Site 21

Seattle, Washington, 98104, United States

Location

Bausch Health Site 14

Seattle, Washington, 98195, United States

Location

Bausch Health Site 20

Milwaukee, Wisconsin, 53226, United States

Location

Related Publications (1)

  • 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.

    PMID: 35750249DERIVED

Results Point of Contact

Title
Study Director
Organization
Bausch Health Americas, Inc
susan.harris@bauschhealth.com
19083009920

Study Officials

  • Angela Bulawski

    Bausch Health

    STUDY DIRECTOR

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
OTHER
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
TRIPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR
Masking Details
Blinding will be maintained in the QD SSD cohorts by administering placebo as the second daily dose.
Purpose
TREATMENT
Intervention Model
PARALLEL
Model Details: Randomized, Double-Blind, Placebo-Controlled, Dose-Ranging, Multicenter Study
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

April 12, 2018

First Posted

May 3, 2018

Study Start

September 13, 2018

Primary Completion

March 12, 2020

Study Completion

March 12, 2020

Last Updated

April 13, 2023

Results First Posted

April 13, 2023

Record last verified: 2023-03

Locations

US(34)