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

Sponsor
Bausch Health Americas, Inc. (Industry)
Overall Status
Completed
CT.gov ID
NCT03515044
Collaborator
(none)
76
Enrollment
34
Locations
5
Arms
17.9
Actual Duration (Months)
2.2
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

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).

Condition or Disease Intervention/Treatment Phase
  • 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
  • Drug: lactulose
 Phase 2

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 Design

Study Type:
Interventional
Actual Enrollment :
76 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Intervention Model Description:
Randomized, Double-Blind, Placebo-Controlled, Dose-Ranging, Multicenter StudyRandomized, Double-Blind, Placebo-Controlled, Dose-Ranging, Multicenter Study
Masking:
Triple (Participant, Care Provider, Investigator)
Masking Description:
Blinding will be maintained in the QD SSD cohorts by administering placebo as the second daily dose.
Primary Purpose:
Treatment
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)
Actual Study Start Date :
Sep 13, 2018
Actual Primary Completion Date :
Mar 12, 2020
Actual Study Completion Date :
Mar 12, 2020

Arms and Interventions

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) and lactulose

Drug: lactulose
to be taken in the recommended adult size dosage.
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) and lactulose

Drug: lactulose
to be taken in the recommended adult size dosage.
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) and lactulose

Drug: lactulose
to be taken in the recommended adult size dosage.
Experimental: Cohort 4 80 mg Rifaximin SSD twice daiy

Cohort 4 80 mg Rifaximin SSD twice daily (BID) and lactulose

Drug: 80 mg Rifaximin SSD twice daily
SSD twice daily (BID) and lactulose

Drug: lactulose
to be taken in the recommended adult size dosage.
Experimental: Cohort 5 Placebo twice daily

SSD placebo twice daily (BID) and lactulose

Drug: Placebo
Administered twice daily (BID) and lactulose

Drug: lactulose
to be taken in the recommended adult size dosage.

Outcome Measures

Primary Outcome Measures

  1. Time to OHE resolution determined using the Hepatic Encephalopathy Grading Instrument (HEGI). [3 to 12 hours after administration]

    Major diagnostic criteria include: (1) disorientation (time, place, and/or person), or (2) presence of both lethargy and asterixis, or (3) coma. Inter- and intra-rater HEGI reproducibility

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years to 75 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
Yes
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).

Contacts and Locations

Locations

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

Sponsors and Collaborators

  • Bausch Health Americas, Inc.

Investigators

  • Study Director: Angela Bulawski, Bausch Health

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Bausch Health Americas, Inc.
ClinicalTrials.gov Identifier:
NCT03515044
Other Study ID Numbers:
  • RNHE2041
First Posted:
May 3, 2018
Last Update Posted:
Mar 11, 2021
Last Verified:
Mar 1, 2021
Individual Participant Data (IPD) Sharing Statement:
Undecided
Plan to Share IPD:
Undecided
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Additional relevant MeSH terms:
Hepatic Encephalopathy
Brain Diseases
Rifaximin
Lactulose

Study Results

No Results Posted as of Mar 11, 2021