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Nonalcoholic Fatty LiverPhase 2NCT04235205

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

A Phase 2 study testing Elobixibat 10mg + cholestyramine powder 9g (cholestyramine 4g) in people with Nonalcoholic Fatty Liver and Nonalcoholic Steatohepatitis, run by Yokohama City University at 1 site in Japan.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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). Read more about this study

Who is it for?
Ages 20 to 75 years
What is being tested?
Elobixibat 10mg + cholestyramine powder 9g (cholestyramine 4g)
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
102 participants
Where
1 siteJapan
Study dates
29 Jan 2020to 30 Sep 2021
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 20 to 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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:
  • Steatosis (scored 0 to 3)
  • Ballooning degeneration (scored 0 to 2)
Show all 17Show fewer
  • Lobular inflammation (scored 0 to 3)
  • The suspected diagnosis of NAFLD/NASH is based on the following criteria:
  • Serum aspartate aminotransferase (AST) ≥20 U/L and alanine aminotransferase (ALT) ≥40 U/L in males or ≥28 U/L in females
  • Waist circumference ≥85 cm in males or ≥90 cm in females
  • 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
  • Fasting serum low density lipoprotein-cholesterol (LDL-C) >120 mg/dL or undergoing antidyslipidemic drugs
  • Be willing to maintain a stable diet and physical activity throughout the course of the study

Who cannot join

  • 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
Show all 40Show fewer
  • 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)
  • Medical history of liver cirrhosis
  • Clinical evidence of portal hypertension to include any history of ascites, hepatic encephalopathy, or presence of esophageal varices
  • Use of drugs historically associated with NAFLD (amiodarone, methotrexate, systemic glucocorticoids, tetracyclines,tamoxifen, estrogens at doses greater than those used for hormone replacement, anabolic steroids, or valproic acid) or other known hepatotoxins for ≥2 weeks in the year prior to Screening
  • Use of the following medications:
  • Glucagon-like peptide-1 (GLP-1) agonists unless on a stable dose 3 months prior to Screening or liver biopsy
  • Ursodeoxycholic acid or thiazolidinediones within 3 months prior to Screening
  • Antidyslipidemic drugs have been stable for ≥3 months prior to Screening
  • Oral antidiabetic drugs have been stable for ≥3 months prior to Screening
  • Agents (including herbal over-the-counter weight loss preparations) or medications known to significantly impact body weight within 3 months prior to Screening
  • History of significant alcohol consumption, defined as an average of≥20g/day in female patients and ≥30 g/day in male patients, for a period of >3 consecutive months within 1 year prior to Screening, hazardous alcohol use (Alcohol Use Disorders Identification Test score ≥8), or an inability to reliably quantify alcohol consumption but determined as alcohol polydipsia based upon judgment of the Investigator or subinvestigator
  • Weight change ≥10% within the 6 months prior to Screening or ≥5% within the 3 months prior to Screening
  • Surgery planned during the study period or after bariatric surgery (e.g., gastroplasty and roux-en-Y gastric bypass)
  • Type 1 diabetes by medical history
  • Uncontrolled Type 2 diabetes defined as hemoglobin A1c (HbA1c) >9.5% at Screening(patients with HbA1c >9.5% may be rescreened) or requiring insulin dose adjustment >10% within 2 months prior to Screening
  • Clinical hyperthyroidism or hypothyroidism or Screening hormone results pointing to thyroid dysfunction. Patients receiving dose-stable thyroid replacement therapy for ≥3 months prior to Screening will be allowed to participate in this study as long as thyroid tests show that the patient is euthyroid and stable
  • History of any condition causing malabsorption such as chronic pancreatitis, extensive bowel/small intestine surgery, celiac disease, or bile flow obstruction
  • History of any condition associated with acute or chronic diarrhea such as inflammatory bowel disease (IBD),functional diarrhea, irritable bowel syndrome (IBS) with predominant diarrhea, IBS with mixed bowel habits, or unclassified IBS
  • Uncontrolled hypertension (either treated or untreated) defined as systolic blood pressure >160 mmHg or a diastolic blood pressure >100 mmHg at Screening
  • History of New York Heart Association (NYHA) Class III or IV heart failure, or known left ventricular ejection fraction <30%
  • History of myocardial infarction, unstable angina, percutaneous coronary intervention, coronary artery bypass graft, or stroke or major surgery within 6 months prior to Screening
  • Active substance abuse, within 1 year prior to Screening
  • Participation in an investigational new drug trial in the 30 days prior to Screening or within 5 half-lives of an investigational agent, whichever is longer
  • Complication with malignancy Patients with a history of malignancies that have been treated with curative intent or completed chemotherapy may be eligible. Patients under evaluation for malignancy are not eligible
  • Known intolerance to MRI or conditions contraindicated for MRI procedures
  • Any other condition which is considered to be inappropriate for the study by the Investigator or subinvestigator

Trial locations and contacts

1 site in 1 country.

Japan1 site

  • Yokohama City University

    Yokohama, Kanagawa, 236-0004

Other trials in Japan

About this study

Official title: Efficacy and Safety of Elobixibat in Combination With Cholestyramine for Patients With Nonalcoholic Fatty Liver Disease: a Single Center, Double-blind, Randomized, Placebo-Controlled, Phase 2a Trial.

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).

Read the detailed description

This is a placebo-controlled, randomized, double-blind, parallel group, comparative study, when patients with nonalcoholic fatty liver disease (NAFLD) or nonalcoholic steatohepatitis (NASH), are administered elobixibat at 10 mg and cholestyramine powder at 9g( cholestyramine 4g) once daily for 16 weeks.

Being tested
Elobixibat 10mg + cholestyramine powder 9g (cholestyramine 4g), Elobixibat 10mg + cholestyramine powder placebo, Elobixibat placebo + cholestyramine powder 9g (cholestyramine 4g), Elobixibat placebo + cholestyramine powder placebo
Keywords
Elobixibat, Cholestyramine, Nonalcoholic fatty liver disease, Nonalcoholic steatohepatitis, phase 2 trial, Combination therapy
Medical subject headings
Non-alcoholic Fatty Liver Disease

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

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

    Also called AJG533 10 mg + CTM27 9 g

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

  • Elobixibat 10mg + cholestyramine powder placeboDrug

    Also called AJG533 10 mg + CTM27 placebo

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

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

    Also called AJG533 placebo + CTM27 9g

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

  • Elobixibat placebo + cholestyramine powder placeboDrug

    Also called AJG533 placebo + CTM27 placebo

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

Study groups in NCT04235205
Study groupRoleWhat they receive
Elobixibat and cholestyramineExperimentalThe investigational product per dosing (elobixibat 10mg and cholestyramine powder 9g) are orally administered once daily for 16 weeks.
Receives: Drug: Elobixibat 10mg + cholestyramine powder 9g (cholestyramine 4g)
ElobixibatExperimentalThe investigational product per dosing (elobixibat 10mg and cholestyramine powder placebo) are orally administered once daily for 16 weeks.
Receives: Drug: Elobixibat 10mg + cholestyramine powder placebo
cholestyramineExperimentalThe investigational product per dosing (elobixibat placebo and cholestyramine powder 9g) are orally administered once daily for 16 weeks.
Receives: Drug: Elobixibat placebo + cholestyramine powder 9g (cholestyramine 4g)
PlaceboPlacebo comparatorThe investigational product per dosing (elobixibat placebo and cholestyramine powder placebo) are orally administered once daily for 16 weeks.
Receives: Drug: Elobixibat placebo + cholestyramine powder placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

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

    Serum

    Measured: Week 16

Secondary outcomes (9)

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

    MRI-PDFF

    Measured: Week 16

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

    MRE

    Measured: Week 16

  3. Change from baseline to Week 16 in ALT level

    Serum

    Measured: Week 16

  4. Change from baseline to Week 16 in AST level

    Serum

    Measured: Week 16

  5. Change from baseline to Week 16 in γ-GTP level

    Serum

    Measured: Week 16

  6. Absolute change from baseline to Week 16 in HDL-C level

    Serum

    Measured: Week 16

  7. Change from baseline to Week 16 in non HDL-C level

    Serum

    Measured: Week 16

  8. Change from baseline to Week 16 in LDL-C/HDL-C ratio

    Serum

    Measured: Week 16

  9. Change from baseline to Week 16 in TG level

    Serum

    Measured: Week 16

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted21 Jan 2020
  2. Study start29 Jan 2020
  3. Primary completion21 Jul 2021
  4. Study completion30 Sep 2021

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Triple blind
Who is masked
Participant, Investigator, Outcomes assessor
Enrolment
102 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04235205
Sponsor's protocol ID
YCU19002
Status last verified
Nov 2021
First submitted
15 Jan 2020
Last updated
16 Nov 2021
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 29805116

  • 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.

    PubMed 32907904

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Elobixibat 10mg + cholestyramine powder 9g (cholestyramine 4g) in people with Nonalcoholic Fatty Liver and Nonalcoholic Steatohepatitis, run by Yokohama City University at 1 site in Japan.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 17 inclusion and 40 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 16 Nov 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Japan. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Absolute change from baseline in serum LDL-C at Week 16 (time frame: Week 16). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04235205, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Nov 2021.

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