Clinical trial NCT03681457: Evaluation of the Pharmacokinetics of Tropifexor in Subjects With Mild, Moderate, or Severe Hepatic Impairment Compared to Healthy Control Subjects
Official title: A Phase 1, Open-label, Single-dose, Multi-center, Parallel Group Study to Evaluate the Pharmacokinetics of Tropifexor (LJN452) in Subjects With Mild, Moderate or Severe Hepatic Impairment Compared to Healthy Control Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Non-alcoholic Fatty Liver Disease
Keywords: LJN452
tropifexor
PK
safety
healthy subjects
hepatically impaired
Nonalcoholic Steatohepatitis
Nonalcoholic Fatty Liver Disease
NAFLD
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2018-09-24
Enrollment: 42
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility 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.

Primary outcomes:
measure: Cmax
timeFrame: Up to 8 days
measure: Tmax
timeFrame: Up to 8 days
measure: AUClast
timeFrame: Up to 8 days
measure: AUCinf
timeFrame: Up to 8 days
measure: T1/2
timeFrame: Up to 8 days
measure: CL/F
timeFrame: Up to 8 days
measure: Vz/F
timeFrame: Up to 8 days
Secondary outcomes:
measure: fu
timeFrame: Day 1
measure: Cmax,u
timeFrame: Day 1
measure: AUClast,u
timeFrame: Day 1
measure: AUCinf,u
timeFrame: Day 1
measure: CL/F,u
timeFrame: Day 1
Other outcomes:
Locations:
city: Orlando
country: United States
facility: Novartis Investigative Site
state: Florida
city: Orlando
country: United States
facility: Novartis Investigative Site
state: Florida
city: Knoxville
country: United States
facility: Novartis Investigative Site
state: Tennessee
Study officials:
References: