Effect of LIK066 on Reduction of Fatty Content in Livers of Obese Patients

NCT03205150 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: CLIK066X22042017-002046-71
• Study Type: interventional
• Target: 107
• Locations: 8 countries
• Sites: 15

Brief Summary

The purpose of this study was to assess the effects of LIK066 on a variety of metabolic and inflammation biomarkers in patients with non-alcoholic steatohepatitis (NASH)

Conditions

Obese Patients With Non-alcoholic Steatohepatitis (NASH)

Keywords

non-alcoholic steatohepatitis; NASH; Obese; Type 2 diabetes mellitus; non-alcoholic fatty liver disease

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in Alanine Aminotransferase (ALT) at Week 12

  Alanine aminotransferase (ALT) is an enzyme found primarily in the liver. ALT is increased with liver damage. In this study, the blood levels of ALT was used to detect liver injury. Baseline is defined as the mean of measurements taken at the Screening and Baseline visits.

  Baseline, Week 12

Secondary Outcomes (10)

• Change From Baseline in Percent Liver Fat at Week 12

  Baseline, Week 12

• Percent Change From Baseline in Total Body Weight at Week 12

  Baseline, Week 12

• Change From Baseline in Non-invasive Markers of Hepatic Fibrosis: Enhanced Liver Fibrosis Test (ELF) Score at Week 12

  Baseline, Week 12

• Change From Baseline in the Concentration of Hyaluronic Acid at Week 12.

  Baseline, Week 12

• Change From Baseline in the Concentration of Procollagen Type Iii N-Terminal Peptide (PIIINP) at Week 12.

  Baseline, Week 12

Study Arms (3)

LIK066 30 mg

EXPERIMENTAL

Film coated tablet of LIK066 30 mg was mostly administered once daily before lunch, except on Day 56 when it was administered before breakfast and in fasted state on Day 84.

Drug: LIK066

LIK066 150 mg

EXPERIMENTAL

Film coated tablet of LIK066 150 mg was mostly administered once daily before lunch, except on Day 56 when it was administered before breakfast and in fasted state on Day 84

Drug: LIK066

Placebo

EXPERIMENTAL

LIK066 0 mg film-coated tablet(Placebo matching tablets) was mostly administered once daily before lunch, except on Day 56 when it was administered before breakfast and in fasted state on Day 84.

Drug: Placebo

Interventions

LIK066 DRUG

Film coated tablet of LIK066 either 30mg or 150 mg was mostly administered once daily before lunch, except on Day 56 when it was administered before breakfast and in fasted state on Day 84

LIK066 150 mg; LIK066 30 mg

Placebo DRUG

LIK066 0 mg film-coated tablet(Placebo matching tablets) was mostly administered once daily before lunch, except on Day 56 when it was administered before breakfast and in fasted state on Day 84.

Placebo

Eligibility Criteria

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

You may qualify if:

• EITHER
• Histologic confirmed NASH based on liver biopsy obtained 2 years or less before randomization with a fibrosis level of F1, F2 or F3 in the absence of a histological diagnosis of alternative chronic liver disease AND ALT greater than or equal to 50 IU/L (males) or greater than or equal to 35 IU/L (females) at screening.
• Phenotypic diagnosis of NASH based on presence of ALL three of the following at screening:
• ALT greater than or equal to 50IU/L (males) or greater than or equal to 35 IU/L (females) AND
• BMI greater than or equal to 27 kg/m\^2 (in patients with a self-identified race other than Asian) or greater than or equal to 23 kg/m\^2 (in patients with a self identified Asian race) AND
• Diagnosis of Type 2 diabetes mellitus by HbA1c: greater than or equal to 6.5 % and less than or equal to 10%
• Patients must weigh no more than 150 kg (330 lbs) to participate in the study.
• Male and female patients 18 years or older at the time of screening visit.

You may not qualify if:

• History or presence of other concomitant liver diseases
• History or current diagnosis of ECG abnormalities
• Use of GLP-1 agonists, SGLT2 inhibitors, TZDs, FXR agonists and any pharmacologically active weight loss drugs within 6 weeks of screening and until end of study
• Patients with contraindications to MRI imaging
• Current or history of significant alcohol consumption
• Clinical evidence of hepatic decompensation or severe liver impairment
• Women of child bearing potential (unless on basic contraception methods)
• Presence of liver cirrhosis

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (15)

Novartis Investigative Site

Baton Rouge, Louisiana, 70808, United States

Location

Novartis Investigative Site

St Louis, Missouri, 63110, United States

Location

Novartis Investigative Site

Knoxville, Tennessee, 37920, United States

Location

Novartis Investigative Site

Live Oak, Texas, 78233, United States

Location

Novartis Investigative Site

CABA, Buenos Aires, C1056ABJ, Argentina

Location

Novartis Investigative Site

Buenos Aires, C1120AAC, Argentina

Location

Novartis Investigative Site

Montreal, Quebec, H3P 3P1, Canada

Location

Novartis Investigative Site

Haifa, 343621, Israel

Location

Novartis Investigative Site

Ramat Gan, Israel

Location

Novartis Investigative Site

Tel Aviv, 64239, Israel

Location

Novartis Investigative Site

Leiden, 2333 CL, Netherlands

Location

Novartis Investigative Site

Saint Petersburg, 194358, Russia

Location

Novartis Investigative Site

Chiayi City, 60002, Taiwan

Location

Novartis Investigative Site

Tainan, 70403, Taiwan

Location

Novartis Investigative Site

Bangkok, 10700, Thailand

Location

Related Publications (1)

• Harrison SA, Manghi FP, Smith WB, Alpenidze D, Aizenberg D, Klarenbeek N, Chen CY, Zuckerman E, Ravussin E, Charatcharoenwitthaya P, Cheng PN, Katchman H, Klein S, Ben-Ari Z, Mendonza AE, Zhang Y, Martic M, Ma S, Kao S, Tanner S, Pachori A, Badman MK, He Y, Ukomadu C, Sicard E. Licogliflozin for nonalcoholic steatohepatitis: a randomized, double-blind, placebo-controlled, phase 2a study. Nat Med. 2022 Jul;28(7):1432-1438. doi: 10.1038/s41591-022-01861-9. Epub 2022 Jun 20.

  PMID: 35725922 DERIVED

Related Links

• A Plain Language Trial Summary is available on novartisclinicaltrials.com

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease; Obesity; Diabetes Mellitus, Type 2

Interventions

licogliflozin

Condition Hierarchy (Ancestors)

Fatty Liver; Liver Diseases; Digestive System Diseases; Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

Novartis.email@novartis.com

862-778-8300

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
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 28, 2017
• First Posted: July 2, 2017
• Study Start: October 4, 2017
• Primary Completion: November 11, 2019
• Study Completion: November 14, 2019
• Last Updated: October 8, 2021
• Results First Posted: January 6, 2021

Record last verified: 2021-10

Data Sharing

• IPD Sharing: Will share

Locations

CA (1); TH (1); TW (2); US (4); IL (3); NL (1); RU (1); AR (2)