Non-alcoholic Fatty Liver DiseasePhase 1NCT03681457
Evaluation of the Pharmacokinetics of Tropifexor in Subjects With Mild, Moderate, or Severe Hepatic Impairment Compared to Healthy Control Subjects
A Phase 1 study testing LJN452 in people with Non-alcoholic Fatty Liver Disease, run by Novartis Pharmaceuticals at 3 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 70 yearsHealthy volunteers can take part
- Conditions the study is for
- Non-alcoholic Fatty Liver Disease
- What is being tested?
- LJN452
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 42 participants
- Where
- 3 sitesUnited States
- Study dates
- 24 Sep 2018to 25 Sep 2019
- Phase
- Phase 1
- 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 18 to 70 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- In good health as determined by past medical history, physical examination, ECG, laboratory tests, and urinalysis at Screening.
- Hepatic impairment as defined by the Child-Pugh classification for severity of liver disease
Who cannot join
- 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:
- Liver disease or liver injury
Show all 14Show fewer
- Chronic infection with Hepatitis B or Hepatitis C
- History or presence of impaired renal function
- Hepatically Impaired Subjects:
- 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 locations and contacts
3 sites in 1 country.
United States3 sites
Novartis Investigative Site
Knoxville, Tennessee, 37920
Novartis Investigative Site
Orlando, Florida, 32806
Novartis Investigative Site
Orlando, Florida, 32809
About this study
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
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.
- Conditions
- Non-alcoholic Fatty Liver Disease
- Being tested
- LJN452
- Keywords
- LJN452, tropifexor, PK, safety, healthy subjects, hepatically impaired, Nonalcoholic Steatohepatitis, Nonalcoholic Fatty Liver Disease, NAFLD
- 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.
LJN452Drug
Dose A single dose
| Study group | Role | What they receive |
|---|---|---|
| Group 1 - Normal Hepatic Function | Other | Normal hepatic function - Control - control group Receives: Drug: LJN452 |
| Group 2 - Mild Hepatic Impairment | Experimental | Mild hepatic impairment - Child-Pugh A (Score 5-6) Receives: Drug: LJN452 |
| Group 3 - Moderate Hepatic Impairment | Experimental | Moderate hepatic impairment - Child-Pugh B (Score 7-9) Receives: Drug: LJN452 |
| Group 4 - Severe Hepatic Impairment | Experimental | Severe hepatic impairment - Child-Pugh C (score 10-15) Receives: Drug: LJN452 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cmax
The maximum (peak) observed drug concentration after single dose administration (mass x volume-1)
Measured: Up to 8 days
Tmax
Time to reach the maximum (peak) plasma drug concentration after single dose administration (time)
Measured: Up to 8 days
AUClast
The area under the concentration-time curve from time zero to the time of the last quantifiable concentration sampling time (mass x time x volume-1)
Measured: Up to 8 days
AUCinf
The area under the concentration-time curve from time zero to infinity (mass x time x volume-1)
Measured: Up to 8 days
T1/2
The elimination half-life associated with the terminal slope of a semi-logarithmic concentration-time curve
Measured: Up to 8 days
CL/F
The apparent total body clearance of the drug from plasma (volume x time-1)
Measured: Up to 8 days
Vz/F
The apparent volume of distribution during the terminal phase
Measured: Up to 8 days
Secondary outcomes (5)
fu
Fraction of analyte unbound calculated in-vitro
Measured: Day 1
Cmax,u
The maximum (peak) observed plasma drug concentration after single dose administration (Cmax) of unbound drug (mass x time x volume-1), calculated as Cmax*fu
Measured: Day 1
AUClast,u
The area under the concentration-time curve from time zero to the last quantifiable concentration sampling time of unbound drug (mass x time x volume-1), calculated as AUClast*fu
Measured: Day 1
AUCinf,u
The area under the concentration-time curve from time zero to infinity of unbound drug (mass x time x volume-1), calculated as AUCinf*fu
Measured: Day 1
CL/F,u
The apparent total body clearance of drug from the plasma of unbound drug (volume x time-1), calculated as CL/F/fu
Measured: Day 1
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Sep 2018
- Study start24 Sep 2018
- Primary completion25 Sep 2019
- Study completion25 Sep 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Non-alcoholic Fatty Liver DiseaseStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 42 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03681457
- Sponsor's protocol ID
- CLJN452A2109
- Status last verified
- Sep 2020
- First submitted
- 11 Sep 2018
- Last updated
- 14 Dec 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 14 Dec 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03681457
- Acronym / sponsor ID
- CLJN452A2109
- Conditions
- Non-alcoholic Fatty Liver Disease
- Keywords
- LJN452, tropifexor, PK, safety, healthy subjects, hepatically impaired, Nonalcoholic Steatohepatitis, Nonalcoholic Fatty Liver Disease
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 42 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 24 Sep 2018 (actual)
- Primary completion
- 25 Sep 2019 (actual)
- Study completion
- 25 Sep 2019 (actual)
- First posted
- 24 Sep 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Group 1 - Normal Hepatic Function | Other | Drug: LJN452Normal hepatic function - Control - control group |
| Group 2 - Mild Hepatic Impairment | Experimental | Drug: LJN452Mild hepatic impairment - Child-Pugh A (Score 5-6) |
| Group 3 - Moderate Hepatic Impairment | Experimental | Drug: LJN452Moderate hepatic impairment - Child-Pugh B (Score 7-9) |
| Group 4 - Severe Hepatic Impairment | Experimental | Drug: LJN452Severe hepatic impairment - Child-Pugh C (score 10-15) |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- In good health as determined by past medical history, physical examination, ECG, laboratory tests, and urinalysis at Screening.
- Hepatic impairment as defined by the Child-Pugh classification for severity of liver disease
Key exclusion criteria (14 listed)
- 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
- Liver disease or liver injury
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| LJN452Dose A single dose | Drug | Group 1 - Normal Hepatic Function, Group 2 - Mild Hepatic Impairment, Group 3 - Moderate Hepatic Impairment, Group 4 - Severe Hepatic Impairment |
Primary outcome
Cmax
Time frame: Up to 8 days
The maximum (peak) observed drug concentration after single dose administration (mass x volume-1)
Tmax
Time frame: Up to 8 days
Time to reach the maximum (peak) plasma drug concentration after single dose administration (time)
AUClast
Time frame: Up to 8 days
The area under the concentration-time curve from time zero to the time of the last quantifiable concentration sampling time (mass x time x volume-1)
AUCinf
Time frame: Up to 8 days
The area under the concentration-time curve from time zero to infinity (mass x time x volume-1)
T1/2
Time frame: Up to 8 days
The elimination half-life associated with the terminal slope of a semi-logarithmic concentration-time curve
CL/F
Time frame: Up to 8 days
The apparent total body clearance of the drug from plasma (volume x time-1)
Vz/F
Time frame: Up to 8 days
The apparent volume of distribution during the terminal phase
5 secondary outcomes
fu
Time frame: Day 1
Cmax,u
Time frame: Day 1
AUClast,u
Time frame: Day 1
AUCinf,u
Time frame: Day 1
CL/F,u
Time frame: Day 1
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Dec 2020.
- Results for CCLJN452A2109 can be found on the Novartis Clinical Trial Results WebsiteLink provided by the sponsor.
- A Plain Language Trial Summary is available on novartisclinicaltrials.comLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing LJN452 in people with Non-alcoholic Fatty Liver Disease, run by Novartis Pharmaceuticals at 3 sites in United States.
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 2 inclusion and 14 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 14 Dec 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States. 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. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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?
Cmax (time frame: Up to 8 days). The study lists 7 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 14 Dec 2020.