Pharmacokinetics Study of TNO155 in Participants With Mild, Moderate, or Severe Renal Impairment Compared to Matched Healthy Participants

Renal Impairment Clinical Trial

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 Renal Impairment Compared to Matched Healthy Control Participants

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT05541159
• Other study ID #: CTNO155A12105
• Status: Withdrawn
• Phase: Phase 1
• Start date: March 19, 2025
• Est. completion date: July 15, 2025

Study information

• Verified date: February 2024
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this Phase 1 study is to evaluate the effect of various degrees of renal 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 renal impairment

Description:

This is a study to evaluate the PK of TNO155 in participants with mild, moderate or severe renal impairment compared to matched healthy control participants with normal renal function. The study will be divided into 2 parts. Participants in the renal impairment groups will be staged by their respective degree of renal function (mild, moderate, or severe) according to the estimated glomerular filtration rate (eGFR) determined at the screening visit. Each renal impairment participant must be matched to a healthy control participant with respect to age (±10 years), body weight (±20%) and sex. Each participant in the healthy control group (Group 1) can be matched to one or more participants from any renal impairment group (Groups 2, 3, and 4).

On Day 1 morning, participants will receive a single oral dose of TNO155 .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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: July 15, 2025
• Est. primary completion date: July 15, 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

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. Must be a non-smoker or and agree to remain a non-smoker from screening until the End of Study.

Group 1

•eGFR as determined by Chronic Kidney Disease Epidemiology Collaboration [CKD EPI] equation and conversion within normal range as determined by GFR 90 mL/min at screening and baseline.

Groups 2 to 4

• Participants with different levels of impaired renal function satisfying criteria for renal impairment as determined at screening by the eGFR at screening

• Participants must have documented stable renal disease without evidence of renal progressive disease

Exclusion Criteria:

All Participants

• Use of drugs (prescription, non-prescription and herbal remedies such as St John's wort), within 4 weeks prior to dosing until completion of the End of Study Visit.

• Participant has received a renal transplant at any time in the past and is on immunosuppressant therapy Left ventricular ejection fraction (LVEF) < 50% or below the institutional standard lower limit, at screening or baseline.

• Uncontrolled hypertension despite medical treatment at screening or baseline. Group 1

• Significant illness, which has not been resolved within 2 weeks prior to dosing of study treatment.

• History or presence of renal disease or kidney injury Groups 2, 3 and 4

• Severe albuminuria

• Other laboratory values grade 2 severity according to NCI Common Terminology Criteria for Adverse Events (NCI-CTCAE)

• Participants undergoing any method of dialysis.

• Participants with renal impairment due to hepatic disease (hepatorenal syndrome).

Other protocol-defined inclusion/exclusion criteria may apply

Related Conditions & MeSH terms

• Renal Impairment
• Renal Insufficiency

Intervention

Drug:
• TNO155
Single oral dose of TNO155 on Day 1

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals	Pharmaceutical Research Associates

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Up to 240 hours post single dose
Primary	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.	AUC from time zero to time "t" (AUC0-t) of TNO155
Primary	AUC from time zero to infinity (AUCinf) of TNO155	AUCinf will be calculated based on TNO155 plasma concentrations and non-compartmental methods.	Up to 240 hours post single dose
Primary	Maximum (peak) observed plasma concentration (Cmax) of TNO155	Cmax will be calculated based on TNO155 plasma concentrations and non-compartmental methods.	Up to 240 hours post single dose
Primary	Time to reach maximum observed plasma concentration (Tmax) of TNO155	Tmax will be calculated based on TNO155 plasma concentrations and non-compartmental methods	Up to 240 hours post single dose
Primary	Elimination half-life (T1/2) of TNO155	T1/2 will be calculated based on TNO155 plasma concentrations and non-compartmental methods.	Up to 240 hours post single dose
Primary	Sampling time of the last measurable plasma concentration (Tlast) of TNO155	Tlast will be calculated based on TNO155 plasma concentrations and non-compartmental methods.	Up to 240 hours post single dose
Primary	Apparent plasma clearance (CL/F) of TNO155	CL/F will be calculated based on TNO155 plasma concentrations and non-compartmental methods.	Up to 240 hours post single dose
Primary	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.	Up to 240 hours post single dose
Secondary	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.	Up to 30 days post single dose
Secondary	Unbound Cmax (Cmax,u) of TNO155	Cmax,u will be calculated based on the unbound fraction of TNO155 in plasma.	Up to 240 hours post single dose
Secondary	Unbound AUClast (AUClast,u) of TNO155	AUClast,u will be calculated based on the unbound fraction of TNO155 in plasma.	Up to 240 hours post single dose
Secondary	Unbound AUCinf (AUCinf,u) of TNO155	AUCinf,u will be calculated based on the unbound fraction of TNO155 in plasma	Up to 240 hours post single dose
Secondary	Unbound CL/F (CL/F,u) of TNO155	CL/F,u will be calculated based on the unbound fraction of TNO155 in plasma.	Up to 240 hours post single dose
Secondary	Renal clearance (CLr) of TNO155	CLr will be calculated based on urinary excretion data of TNO155.	Up to 240 hours post single dose
Secondary	Apparent non-renal clearance (CLNR/F) of TNO155	CLNR/F will be calculated based on urinary excretion data of TNO155.	Up to 240 hours post single dose
Secondary	Fraction of dose excreted in urine (fe) of TNO155	Fe will be calculated based on urinary excretion data of TNO155.	Up to 240 hours post single dose