Evaluation of the Pharmacokinetics of Tropifexor in Subjects With Mild, Moderate, or Severe Hepatic Impairment Compared to Healthy Control Subjects

Novartis

Status and phase: Completed; Phase 1

Conditions: Non-alcoholic Fatty Liver Disease

Treatments: Drug: LJN452

Study type: Interventional

Funder types: Industry

Identifiers

NCT03681457

CLJN452A2109

Details and patient eligibility

About

The primary purpose of this study is to evaluate the effect of hepatic impairment on the systemic exposure of tropifexor and to evaluate the safety of tropifexor in subjects with hepatic impairment. The results of this study will support treatment and dosing decisions for patients with varying degrees of hepatic impairment.

Enrollment: 42 patients

Sex: All

Ages: 18 to 70 years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion criteria

All subjects:

Inclusions Criteria:

• Subjects must weight at least 50 kg, with a BMI within the range of 18 to 38 kg/m2
• Must be willing to remain in the clinical research unit as required by the protocol

Exclusion Criteria:

• Use of other study drugs at the time of enrollment, or within 5 half-lives of enrollment, or within 30 days, whichever is longer; or longer if required by local regulations
• History of hypersensitivity to the study treatment or to drugs of similar chemical classes
• Pregnant or nursing women
• Women of child-bearing potential

Healthy Volunteers:

Inclusion Criteria:

• In good health as determined by past medical history, physical examination, ECG, laboratory tests, and urinalysis at Screening.

Exclusion Criteria:

• Liver disease or liver injury
• Chronic infection with Hepatitis B or Hepatitis C
• History or presence of impaired renal function

Hepatically Impaired Subjects:

Inclusion Criteria:

• Hepatic impairment as defined by the Child-Pugh classification for severity of liver disease

Exclusion Criteria:

• Severe complications of liver disease within the preceding 3 months
• Emergency room visit or hospitalization due to liver disease within the preceding 3 months for mildly and moderately hepatically impaired subjects, and within the preceding 1 month for severely hepatically impaired subjects
• Subject has received liver transplant at any time in the past and is on immunosuppressant therapy
• Acute Hepatitis B or Hepatitis C infection

Other protocol-defined inclusion/exclusion criteria may apply.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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42 participants in 4 patient groups

Group 1 - Normal Hepatic Function

Other group

Description:

Normal hepatic function - Control - control group

Treatment:

Drug: LJN452

Group 2 - Mild Hepatic Impairment

Experimental group

Description:

Mild hepatic impairment - Child-Pugh A (Score 5-6)

Treatment:

Drug: LJN452

Group 3 - Moderate Hepatic Impairment

Experimental group

Description:

Moderate hepatic impairment - Child-Pugh B (Score 7-9)

Treatment:

Drug: LJN452

Group 4 - Severe Hepatic Impairment

Experimental group

Description:

Severe hepatic impairment - Child-Pugh C (score 10-15)

Treatment:

Drug: LJN452