Efficacy and Safety of Elobixibat in Combination With Cholestyramine for Nonalcoholic Fatty Liver Disease

NCT04235205 | Completed Phase 2 DMC

• 1 other identifier: YCU19002
• Study Type: interventional
• Target: 102
• Locations: 1 country
• Sites: 1

Brief Summary

The objective is to evaluate the efficacy and safety of once-daily oral doses of 10 mg elobixibat in combination with 9g cholestyramine powder (cholestyramine 4g) in patients with nonalcoholic fatty liver disease (NAFLD) or nonalcoholic steatohepatitis (NASH).

Conditions

Nonalcoholic Fatty Liver; Nonalcoholic Steatohepatitis

Keywords

Elobixibat; Cholestyramine; Nonalcoholic fatty liver disease; Nonalcoholic steatohepatitis; phase 2 trial; Combination therapy

Outcome Measures

Primary Outcomes (1)

• Absolute change from baseline in serum LDL-C at Week 16

  Serum

  Week 16

Secondary Outcomes (9)

• Absolute change from baseline to Week 16 in the liver fat fraction (%) as measured by MRI-PDFF

  Week 16

• Absolute change from baseline to Week 16 in hepatic fibrosis as measured by MRE

  Week 16

• Change from baseline to Week 16 in ALT level

  Week 16

• Change from baseline to Week 16 in AST level

  Week 16

• Change from baseline to Week 16 in γ-GTP level

  Week 16

Study Arms (4)

Elobixibat and cholestyramine

EXPERIMENTAL

The investigational product per dosing (elobixibat 10mg and cholestyramine powder 9g) are orally administered once daily for 16 weeks.

Drug: Elobixibat 10mg + cholestyramine powder 9g (cholestyramine 4g)

Elobixibat

EXPERIMENTAL

The investigational product per dosing (elobixibat 10mg and cholestyramine powder placebo) are orally administered once daily for 16 weeks.

Drug: Elobixibat 10mg + cholestyramine powder placebo

cholestyramine

EXPERIMENTAL

The investigational product per dosing (elobixibat placebo and cholestyramine powder 9g) are orally administered once daily for 16 weeks.

Drug: Elobixibat placebo + cholestyramine powder 9g (cholestyramine 4g)

Placebo

PLACEBO COMPARATOR

The investigational product per dosing (elobixibat placebo and cholestyramine powder placebo) are orally administered once daily for 16 weeks.

Drug: Elobixibat placebo + cholestyramine powder placebo

Interventions

Elobixibat 10mg + cholestyramine powder 9g (cholestyramine 4g) DRUG

Patients with nonalcoholic fatty liver disease are administered Elobixibat 10mg + cholestyramine powder 9g (cholestyramine 4g) for 16 weeks

Also known as: AJG533 10 mg + CTM27 9 g

Elobixibat and cholestyramine

Elobixibat 10mg + cholestyramine powder placebo DRUG

Patients with nonalcoholic fatty liver disease are administered Elobixibat 10mg+ cholestyramine powder placebo for 16 weeks

Also known as: AJG533 10 mg + CTM27 placebo

Elobixibat

Elobixibat placebo + cholestyramine powder 9g (cholestyramine 4g) DRUG

Patients with nonalcoholic fatty liver disease are administered Elobixibat placebo+ cholestyramine powder 9g (cholestyramine 4g) for 16 weeks

Also known as: AJG533 placebo + CTM27 9g

cholestyramine

Elobixibat placebo + cholestyramine powder placebo DRUG

Patients with nonalcoholic fatty liver disease are administered Elobixibat placebo+ cholestyramine powder placebo for 16 weeks

Also known as: AJG533 placebo + CTM27 placebo

Placebo

Eligibility Criteria

• Age: 20 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients who received adequate explanation about this study and provided written informed consent
• Patients who are ≥ 20 and \< 75 years of age at the time of informed consent
• Patients who have a current biopsy-confirmed NASH within 8 months of screening or a suspected diagnosis of NAFLD/NASH based on the criteria outlined below:
• Biopsy-confirmed NASH is defined as histological NASH diagnosis with fibrosis stage F1 through F3 and a NAFLD activity score (NAS) of ≥4 with a score of ≥1 in each of the NAS components below as assessed by a pathologist using the NASH Clinical Research Network criteria:
• i. Steatosis (scored 0 to 3)
• ii. Ballooning degeneration (scored 0 to 2)
• iii. Lobular inflammation (scored 0 to 3)
• The suspected diagnosis of NAFLD/NASH is based on the following criteria:
• i. Serum aspartate aminotransferase (AST) ≥20 U/L and alanine aminotransferase (ALT) ≥40 U/L in males or ≥28 U/L in females
• ii. Waist circumference ≥85 cm in males or ≥90 cm in females
• iii. Diagnosis of metabolic syndrome having 2 or more of the following 3 risk factors at Screening:
• Fasting plasma glucose ≥110 mg/dL or undergoing drug treatment for elevated glucose
• Systolic blood pressure ≥130 mmHg and/or diastolic blood pressure≥85mmHg or undergoing drug treatment for hypertension, or antihypertensive drug treatment in a patient with a history of hypertension
• Triglycerides (TGs) ≥150 mg/dL or undergoing drug treatment for elevated triglycerides,and/or high-density lipoprotein-cholesterol (HDL-C)\<40mg/dL or undergoing drug treatment for reduced HDL-C
• Screening Magnetic Resonance Imaging (MRI) -Proton Density Fat Fraction (PDFF) with ≥8% liver steatosis

You may not qualify if:

• Women who are pregnant, breastfeeding, possibly pregnant or do not agree to use birth control during the study
• Body mass index (BMI) \<23 kg/m²
• Magnetic Resonance Elastography (MRE) value \>6.7 kPa
• Any of the following laboratory abnormalities:
• ALT \>5 × upper limit normal (ULN) or AST \>5 × ULN
• Prothrombin time - international normalized ratio (PT-INR) ≥1.3 unless on anticoagulant therapy
• Total bilirubin \> ULN, except with an established diagnosis of Gilbert's syndrome
• Platelet count \< 80,000/μL
• eGFR \<45 as calculated by the body surface area (BSA) adjustment (normalized eGFR)
• Acute or chronic liver disease other than NAFLD/NASH including but not limited to the following:
• Hepatitis B (as defined by the presence of hepatitis B surface \[HBs\] antigen at Screening) or hepatitis C(as defined by the presence of hepatitis C virus \[HCV\] antibody \[anti-HCV\]) Patients with positive anti-HCV who test negative for HCV ribonucleic acid (HCV-RNA) at Screening will be allowed to participate in the study as long as there is evidence of viral negativity for a minimum of 12 months prior to Screening
• Evidence of autoimmune hepatitis
• History of primary biliary cholangitis, primary sclerosing cholangitis, Wilson's disease, alpha-1-anti-trypsin deficiency, hemochromatosis or iron overload, drug-induced or alcoholic liver disease, or known bile duct obstruction.
• Suspected or proven hepatocellular carcinoma
• Known history of human immunodeficiency virus (HIV)

Sponsors & Collaborators

• Yokohama City University: lead
• EA Pharma Co., Ltd.: collaborator

Study Sites (1)

Yokohama City University

Yokohama, Kanagawa, 236-0004, Japan

Location

Related Publications (2)

• Nakajima A, Seki M, Taniguchi S, Ohta A, Gillberg PG, Mattsson JP, Camilleri M. Safety and efficacy of elobixibat for chronic constipation: results from a randomised, double-blind, placebo-controlled, phase 3 trial and an open-label, single-arm, phase 3 trial. Lancet Gastroenterol Hepatol. 2018 Aug;3(8):537-547. doi: 10.1016/S2468-1253(18)30123-7. Epub 2018 May 25.

  PMID: 29805116 RESULT

• Kessoku T, Kobayashi T, Ozaki A, Iwaki M, Honda Y, Ogawa Y, Imajo K, Saigusa Y, Yamamoto K, Yamanaka T, Usuda H, Wada K, Yoneda M, Saito S, Nakajima A. Rationale and design of a randomised, double-blind, placebo-controlled, parallel-group, investigator-initiated phase 2a study to investigate the efficacy and safety of elobixibat in combination with cholestyramine for non-alcoholic fatty liver disease. BMJ Open. 2020 Sep 9;10(9):e037961. doi: 10.1136/bmjopen-2020-037961.

  PMID: 32907904 DERIVED

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease

Interventions

elobixibat; Cholestyramine Resin

Condition Hierarchy (Ancestors)

Fatty Liver; Liver Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Polystyrenes; Plastics; Polymers; Macromolecular Substances; Biomedical and Dental Materials; Manufactured Materials; Technology, Industry, and Agriculture

Study Officials

• Takaomi Kessoku, MD.,PhD.

  Yokohama City University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Department of palliative care center

Study Record Dates

• First Submitted: January 15, 2020
• First Posted: January 21, 2020
• Study Start: January 29, 2020
• Primary Completion: July 21, 2021
• Study Completion: September 30, 2021
• Last Updated: November 16, 2021

Record last verified: 2021-11

Data Sharing

• IPD Sharing: Will not share

Locations

JP (1)