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

NCT05541159 | Withdrawn Phase 1 FDA Drug

• 1 other identifier: CTNO155A12105
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief 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

Conditions

Renal Impairment

Keywords

TNO155; renal Impairment; SHP2

Outcome Measures

Primary Outcomes (9)

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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 Outcomes (8)

• Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs)

  Up to 30 days post single dose

• Unbound Cmax (Cmax,u) of TNO155

  Up to 240 hours post single dose

• Unbound AUClast (AUClast,u) of TNO155

  Up to 240 hours post single dose

• Unbound AUCinf (AUCinf,u) of TNO155

  Up to 240 hours post single dose

• Unbound CL/F (CL/F,u) of TNO155

  Up to 240 hours post single dose

Study Arms (4)

Group 1

EXPERIMENTAL

Healthy control participants with normal renal function

Drug: TNO155

Group 2

EXPERIMENTAL

Mild renal impairment

Drug: TNO155

Group 3

EXPERIMENTAL

Moderate renal impairment

Drug: TNO155

Group 4

EXPERIMENTAL

Severe renal impairment

Drug: TNO155

Interventions

TNO155 DRUG

Single oral dose of TNO155 on Day 1

Group 1; Group 2; Group 3; Group 4

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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).

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead
• Pharmaceutical Research Associates: collaborator

MeSH Terms

Conditions

Renal Insufficiency

Condition Hierarchy (Ancestors)

Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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 determined at the screening visit. Healthy participants who were identified and enrolled as matching partners for a renal impairment group in Part I can serve as matching partners for participants in renal impairment group (Group 4) 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 renal impairment as well as healthy control participants Part II: will include participants with severe renal impairment, if allowed after results of interim analysis (IA) obtained for mild and moderate groups.

Study Record Dates

• First Submitted: September 12, 2022
• First Posted: September 15, 2022
• Study Start: March 19, 2025
• Primary Completion: July 15, 2025
• Study Completion: July 15, 2025
• Last Updated: February 29, 2024

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will not share