Hepatic ImpairmentPhase 1NCT05490030
Pharmacokinetics of TNO155 in Participants With Mild, Moderate, or Severe Hepatic Impairment Compared to Matched Healthy Participants
A Phase 1 study testing TNO155 in people with Hepatic Impairment, run by Novartis Pharmaceuticals.
Trial summary
The purpose of this study is to evaluate the effect of various degrees of hepatic impairment on plasma pharmacokinetics (PK), safety and tolerability of TNO155. The results of this study will guide the Novartis recommendation regarding whether or not a dose adjustment may be needed when treating patients with hepatic… Read more about this study
- Who is it for?
- Ages 18 to 75 yearsHealthy volunteers can take part
- Conditions the study is for
- Hepatic Impairment
- What is being tested?
- TNO155
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- 6 Mar 2025to 26 Jun 2025
- 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 75 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- All participants Participants must weigh at least 50 kg and no more than 120 kg and must have a body mass index (BMI) within the range of 18.0 to 38.0 kg/m2, inclusive, for healthy participants. For participants with hepatic impairment without overt ascites, the BMI should be within the range of 18.0 to 40.0 kg/m2. For participants with hepatic impairment with overt ascites, the BMI should be within the range of 18.0 to 45.0 kg/m2.
- Group 1
- •Each healthy control participant must match in age (± 10 years), sex, body weight (± 20%), and smoking status to at least 1 hepatic impairment participant in Groups 2, 3 and/or 4.
- Groups 2 to 4 •Participants with mild, moderate or severe hepatic impairment must have a Child-Pugh score clinically determined at screening and confirmed unchanged at baseline calculated as per the Child-Pugh classification in line with the hepatic impairment status of each Group
Who cannot join
- All Participants
- Use of drugs (prescription, non-prescription and herbal remedies such as St John's wort) known to affect CYP3A or UGT1A3, including UGT1A3 inhibitors and inducers and strong and moderate CYP3A inhibitors and inducers, within 4 weeks prior to dosing until completion of the End of Study Visit.
- Acute or chronic hepatitis B or C infection or active infection requiring therapy that will not be completed before screening.
- Left ventricular ejection fraction (LVEF) < 50% or below the institutional standard lower limit, whichever is higher, as determined by multiple gated acquisition (MUGA) scan or Trans-thoracic echocardiography (TTE) at screening or baseline.
- •At screening, history of retinal vein occlusion (RVO) or presence of predisposing factors to RVO or central serous retinopathy, or any other clinically significant ophthalmologic abnormalities determined by an ophthalmologist.
- Group 1
Show all 14Show fewer
- Any single parameter of alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), or alkaline phosphatase (ALP) exceeding 2.5 × upper limit of normal (ULN) or total bilirubin ≥ 1.5 ULN OR any elevation above ULN of more than 1 parameter of ALT, AST, GGT, ALP, or serum bilirubin at screening or baseline.
- Impaired renal function as indicated by clinically significantly abnormal creatinine or blood urea nitrogen and/or other urea values outside local laboratory ranges or abnormal urinary constituents at screening or baseline.
- Groups 2 and 3
- Severe complications of liver disease within the preceding 3 months prior to dosing.
- Hospitalization due to liver disease within the preceding 1 month prior to dosing.
- Participant has received liver transplant at any time in the past and is on immunosuppressant therapy.
- Participants requiring paracentesis more than every 3 weeks for the management of ascites are excluded.
- Other protocol-defined inclusion/exclusion criteria may apply.
About this study
Official title: A Phase 1, Open-label, Single-dose, Multi-center, Parallel Group Study to Evaluate the Pharmacokinetics of TNO155 in Participants With Mild, Moderate, or Severe Hepatic Impairment Compared to Matched Healthy Control Participants
The purpose of this study is to evaluate the effect of various degrees of hepatic impairment on plasma pharmacokinetics (PK), safety and tolerability of TNO155.
The results of this study will guide the Novartis recommendation regarding whether or not a dose adjustment may be needed when treating patients with hepatic impairment.
Read the detailed description
This is a study to evaluate the PK of TNO155 in participants with mild, moderate or severe hepatic impairment compared to matched healthy control participants with normal hepatic function.
The study will be divided into 2 parts. Participants in the hepatic impairment groups will be staged by their respective degree of hepatic impairment (mild, moderate, or severe) according to a classification score determined at the screening visit and confirmed unchanged at the baseline visit.
Each participant in the healthy control group may be matched to 1 or more evaluable participants with hepatic impairment with respect to age (± 10 years), body weight (± 20%), sex and smoking status (smoker vs. non smoker). Each participant in the control group can be matched to participants from any hepatic impairment group but cannot be matched to more than 1 participant from the same hepatic impairment group.
All participants will be domiciled from Day -1 until Day 11. All participants should have a poststudy safety follow-up contact conducted approximately 30 days after administration of study treatment. The study will be considered complete once all the participants have finished the required assessments, dropped out, or been lost to follow-up before completing the required assessments.
- Conditions
- Hepatic Impairment
- Being tested
- TNO155
- Keywords
- Hepatic, Impairment, TNO155, Phase 1, pharmacokinetics, safety, Tolerability, Child-Pug
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TNO155Drug
Single oral dose of TNO155 on Day 1
| Study group | Role | What they receive |
|---|---|---|
| Group 1 (control) | Experimental | Healthy control participants with normal hepatic function Receives: Drug: TNO155 |
| Group 2 (score 5-6) | Experimental | Mild hepatic impairment: Child-Pugh A Receives: Drug: TNO155 |
| Group 3 (score 7-9) | Experimental | Moderate hepatic impairment: Child-Pugh B Receives: Drug: TNO155 |
| Group 4 (score 10-15) | Experimental | Severe hepatic impairment: Child-Pugh C. This group may be opened if allowed by the results of the interim analysis of the Groups 1 to 3. Receives: Drug: TNO155 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Area under the concentration-versus-time curve (AUC) from time zero to the last measurable plasma concentration (AUClast) of TNO155
AUClast will be calculated based on TNO155 plasma concentrations and non-compartmental methods.
Measured: Up to 240 hours post single dose
AUC from time zero to time "t" (AUC0-t) of TNO155
AUC0-t will be calculated as needed based on TNO155 plasma concentrations and non-compartmental methods. The definition of time "t" may be data-driven post-hoc to mitigate treatment bias due to within participant differences in Tlast between the treatments, or may be selected to allow between-study exposure comparisons that use a common time window.
Measured: Up to 240 hours post single dose
AUC from time zero to infinity (AUCinf) of TNO155
AUCinf will be calculated based on TNO155 plasma concentrations and non-compartmental methods.
Measured: Up to 240 hours post single dose
Maximum (peak) observed plasma concentration (Cmax) of TNO155
Cmax will be calculated based on TNO155 plasma concentrations and non-compartmental methods.
Measured: Up to 240 hours post single dose
Time to reach maximum observed plasma concentration (Tmax) of TNO155
Tmax will be calculated based on TNO155 plasma concentrations and non-compartmental methods
Measured: Up to 240 hours post single dose
Elimination half-life (T1/2) of TNO155
T1/2 will be calculated based on TNO155 plasma concentrations and non-compartmental methods.
Measured: Up to 240 hours post single dose
Sampling time of the last measurable plasma concentration (Tlast) of TNO155
Tlast will be calculated based on TNO155 plasma concentrations and non-compartmental methods.
Measured: Up to 240 hours post single dose
Apparent plasma clearance (CL/F) of TNO155
CL/F will be calculated based on TNO155 plasma concentrations and non-compartmental methods.
Measured: Up to 240 hours post single dose
Apparent volume of distribution during terminal phase (Vz/F) of TNO155
Vz/F will be calculated based on TNO155 plasma concentrations and non-compartmental methods.
Measured: Up to 240 hours post single dose
Secondary outcomes (8)
Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs)
Incidence of AEs and SAEs, including changes in vital signs, electrocardiograms (ECGs) and laboratory results qualifying and reported as AEs.
Measured: Up to 30 days post single dose
Unbound Cmax (Cmax,u) of TNO155
Cmax,u will be calculated based on the unbound fraction of TNO155 in plasma.
Measured: Up to 240 hours post single dose
Unbound AUClast (AUClast,u) of TNO155
AUClast,u will be calculated based on the unbound fraction of TNO155 in plasma.
Measured: Up to 240 hours post single dose
Unbound AUCinf (AUCinf,u) of TNO155
AUCinf,u will be calculated based on the unbound fraction of TNO155 in plasma
Measured: Up to 240 hours post single dose
Unbound CL/F (CL/F,u) of TNO155
CL/F,u will be calculated based on the unbound fraction of TNO155 in plasma.
Measured: Up to 240 hours post single dose
Renal clearance (CLr) of TNO155
CLr will be calculated based on urinary excretion data of TNO155.
Measured: Up to 240 hours post single dose
Apparent non-renal clearance (CLNR/F) of TNO155
CLNR/F will be calculated based on urinary excretion data of TNO155.
Measured: Up to 240 hours post single dose
Fraction of dose excreted in urine (fe) of TNO155
Fe will be calculated based on urinary excretion data of TNO155.
Measured: Up to 240 hours post single dose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Aug 2022
- Study start6 Mar 2025 (estimated)
- Primary completion26 Jun 2025 (estimated)
- Study completion26 Jun 2025 (estimated)
Why it stopped: Sponsor's decision
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hepatic ImpairmentStudies 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
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- The study will be divided into 2 parts. Participants in the hepatic impairment groups will be staged by their respective degree of hepatic impairment according to the Child Pugh classification score determined at the screening visit and confirmed unchanged at the baseline visit. Healthy participants who were identified and enrolled as matching partners for a hepatic impairment group in Part I can serve as matching partners for participants in hepatic impairment group in Part II if they fulfilled the matching criteria. Otherwise, additional matched healthy participants will be enrolled. Part I: will include participants with mild and moderate levels of hepatic impairment as well as healthy control participants assigned to the groups Part II: will include participants with severe hepatic impairment.
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Pharmaceutical Research Associates
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05490030
- Sponsor's protocol ID
- CTNO155A12106
- Status last verified
- Feb 2024
- First submitted
- 4 Aug 2022
- Last updated
- 29 Feb 2024
- 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 29 Feb 2024. 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 TNO155 in Participants With Mild, Moderate, or Severe Hepatic Impairment Compared to Matched Healthy Control Participants
- ClinicalTrials.gov ID
- NCT05490030
- Acronym / sponsor ID
- CTNO155A12106
- Conditions
- Hepatic Impairment
- Keywords
- Hepatic, Impairment, TNO155, Phase 1, pharmacokinetics, safety, Tolerability, Child-Pug
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Sponsor's decision
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Collaborators
- Pharmaceutical Research Associates
- Study start
- 6 Mar 2025 (estimated)
- Primary completion
- 26 Jun 2025 (estimated)
- Study completion
- 26 Jun 2025 (estimated)
- First posted
- 5 Aug 2022 (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 purpose of this study is to evaluate the effect of various degrees of hepatic impairment on plasma pharmacokinetics (PK), safety and tolerability of TNO155.
The results of this study will guide the Novartis recommendation regarding whether or not a dose adjustment may be needed when treating patients with hepatic impairment.
Detailed description
This is a study to evaluate the PK of TNO155 in participants with mild, moderate or severe hepatic impairment compared to matched healthy control participants with normal hepatic function.
The study will be divided into 2 parts. Participants in the hepatic impairment groups will be staged by their respective degree of hepatic impairment (mild, moderate, or severe) according to a classification score determined at the screening visit and confirmed unchanged at the baseline visit.
Each participant in the healthy control group may be matched to 1 or more evaluable participants with hepatic impairment with respect to age (± 10 years), body weight (± 20%), sex and smoking status (smoker vs. non smoker). Each participant in the control group can be matched to participants from any hepatic impairment group but cannot be matched to more than 1 participant from the same hepatic impairment group.
All participants will be domiciled from Day -1 until Day 11. All participants should have a poststudy safety follow-up contact conducted approximately 30 days after administration of study treatment. The study will be considered complete once all the participants have finished the required assessments, dropped out, or been lost to follow-up before completing the required assessments.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
- Model description
- The study will be divided into 2 parts. Participants in the hepatic impairment groups will be staged by their respective degree of hepatic impairment according to the Child Pugh classification score determined at the screening visit and confirmed unchanged at the baseline visit. Healthy participants who were identified and enrolled as matching partners for a hepatic impairment group in Part I can serve as matching partners for participants in hepatic impairment group in Part II if they fulfilled the matching criteria. Otherwise, additional matched healthy participants will be enrolled. Part I: will include participants with mild and moderate levels of hepatic impairment as well as healthy control participants assigned to the groups Part II: will include participants with severe hepatic impairment.
| Arm | Type | Receives |
|---|---|---|
| Group 1 (control) | Experimental | Drug: TNO155Healthy control participants with normal hepatic function |
| Group 2 (score 5-6) | Experimental | Drug: TNO155Mild hepatic impairment: Child-Pugh A |
| Group 3 (score 7-9) | Experimental | Drug: TNO155Moderate hepatic impairment: Child-Pugh B |
| Group 4 (score 10-15) | Experimental | Drug: TNO155Severe hepatic impairment: Child-Pugh C. This group may be opened if allowed by the results of the interim analysis of the Groups 1 to 3. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- All participants Participants must weigh at least 50 kg and no more than 120 kg and must have a body mass index (BMI) within the range of 18.0 to 38.0 kg/m2, inclusive, for healthy participants. For participants with hepatic impairment without overt ascites, the BMI should be within the range of 18.0 to 40.0 kg/m2. For participants with hepatic impairment with overt ascites, the BMI should be within the range of 18.0 to 45.0 kg/m2.
- Group 1
- •Each healthy control participant must match in age (± 10 years), sex, body weight (± 20%), and smoking status to at least 1 hepatic impairment participant in Groups 2, 3 and/or 4.
- Groups 2 to 4 •Participants with mild, moderate or severe hepatic impairment must have a Child-Pugh score clinically determined at screening and confirmed unchanged at baseline calculated as per the Child-Pugh classification in line with the hepatic impairment status of each Group
Key exclusion criteria (14 listed)
- All Participants
- Use of drugs (prescription, non-prescription and herbal remedies such as St John's wort) known to affect CYP3A or UGT1A3, including UGT1A3 inhibitors and inducers and strong and moderate CYP3A inhibitors and inducers, within 4 weeks prior to dosing until completion of the End of Study Visit.
- Acute or chronic hepatitis B or C infection or active infection requiring therapy that will not be completed before screening.
- Left ventricular ejection fraction (LVEF) < 50% or below the institutional standard lower limit, whichever is higher, as determined by multiple gated acquisition (MUGA) scan or Trans-thoracic echocardiography (TTE) at screening or baseline.
- •At screening, history of retinal vein occlusion (RVO) or presence of predisposing factors to RVO or central serous retinopathy, or any other clinically significant ophthalmologic abnormalities determined by an ophthalmologist.
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 |
|---|---|---|
| TNO155Single oral dose of TNO155 on Day 1 | Drug | Group 1 (control), Group 2 (score 5-6), Group 3 (score 7-9), Group 4 (score 10-15) |
Primary outcome
Area under the concentration-versus-time curve (AUC) from time zero to the last measurable plasma concentration (AUClast) of TNO155
Time frame: Up to 240 hours post single dose
AUClast will be calculated based on TNO155 plasma concentrations and non-compartmental methods.
AUC from time zero to time "t" (AUC0-t) of TNO155
Time frame: Up to 240 hours post single dose
AUC0-t will be calculated as needed based on TNO155 plasma concentrations and non-compartmental methods. The definition of time "t" may be data-driven post-hoc to mitigate treatment bias due to within participant differences in Tlast between the treatments, or may be selected to allow between-study exposure comparisons that use a common time window.
AUC from time zero to infinity (AUCinf) of TNO155
Time frame: Up to 240 hours post single dose
AUCinf will be calculated based on TNO155 plasma concentrations and non-compartmental methods.
Maximum (peak) observed plasma concentration (Cmax) of TNO155
Time frame: Up to 240 hours post single dose
Cmax will be calculated based on TNO155 plasma concentrations and non-compartmental methods.
Time to reach maximum observed plasma concentration (Tmax) of TNO155
Time frame: Up to 240 hours post single dose
Tmax will be calculated based on TNO155 plasma concentrations and non-compartmental methods
Elimination half-life (T1/2) of TNO155
Time frame: Up to 240 hours post single dose
T1/2 will be calculated based on TNO155 plasma concentrations and non-compartmental methods.
Sampling time of the last measurable plasma concentration (Tlast) of TNO155
Time frame: Up to 240 hours post single dose
Tlast will be calculated based on TNO155 plasma concentrations and non-compartmental methods.
Apparent plasma clearance (CL/F) of TNO155
Time frame: Up to 240 hours post single dose
CL/F will be calculated based on TNO155 plasma concentrations and non-compartmental methods.
Apparent volume of distribution during terminal phase (Vz/F) of TNO155
Time frame: Up to 240 hours post single dose
Vz/F will be calculated based on TNO155 plasma concentrations and non-compartmental methods.
8 secondary outcomes
Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time frame: Up to 30 days post single dose
Unbound Cmax (Cmax,u) of TNO155
Time frame: Up to 240 hours post single dose
Unbound AUClast (AUClast,u) of TNO155
Time frame: Up to 240 hours post single dose
Unbound AUCinf (AUCinf,u) of TNO155
Time frame: Up to 240 hours post single dose
Unbound CL/F (CL/F,u) of TNO155
Time frame: Up to 240 hours post single dose
Renal clearance (CLr) of TNO155
Time frame: Up to 240 hours post single dose
Apparent non-renal clearance (CLNR/F) of TNO155
Time frame: Up to 240 hours post single dose
Fraction of dose excreted in urine (fe) of TNO155
Time frame: Up to 240 hours post single dose
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Feb 2024.
- 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.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing TNO155 in people with Hepatic Impairment, run by Novartis Pharmaceuticals.
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 4 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: withdrawn, as of the sponsor's last update on 29 Feb 2024. Status can change between updates, so confirm with the study contact before making plans.
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 was withdrawn before enrolling participants, so there are no results.
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?
Area under the concentration-versus-time curve (AUC) from time zero to the last measurable plasma concentration (AUClast) of TNO155 (time frame: Up to 240 hours post single dose). The study lists 9 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 29 Feb 2024.