Clinical trial NCT05541159: Pharmacokinetics Study of TNO155 in Participants With Mild, Moderate, or Severe Renal Impairment Compared to Matched Healthy Participants
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
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE1
Conditions: Renal Impairment
Keywords: TNO155
renal Impairment
SHP2
Lead sponsor: Novartis
Sponsor class: INDUSTRY
Collaborators: name: Pharmaceutical Research Associates
First posted: 2022-09-15
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 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.
Primary purpose: DIAGNOSTIC

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

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Area under the concentration-versus-time curve (AUC) from time zero to the last measurable plasma concentration (AUClast) of TNO155
timeFrame: Up to 240 hours post single dose
measure: AUC from time zero to time "t" (AUC0-t) of TNO155
timeFrame: AUC from time zero to time "t" (AUC0-t) of TNO155
measure: AUC from time zero to infinity (AUCinf) of TNO155
timeFrame: Up to 240 hours post single dose
measure: Maximum (peak) observed plasma concentration (Cmax) of TNO155
timeFrame: Up to 240 hours post single dose
measure: Time to reach maximum observed plasma concentration (Tmax) of TNO155
timeFrame: Up to 240 hours post single dose
measure: Elimination half-life (T1/2) of TNO155
timeFrame: Up to 240 hours post single dose
measure: Sampling time of the last measurable plasma concentration (Tlast) of TNO155
timeFrame: Up to 240 hours post single dose
measure: Apparent plasma clearance (CL/F) of TNO155
timeFrame: Up to 240 hours post single dose
measure: Apparent volume of distribution during terminal phase (Vz/F) of TNO155
timeFrame: Up to 240 hours post single dose
Secondary outcomes:
measure: Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: Up to 30 days post single dose
measure: Unbound Cmax (Cmax,u) of TNO155
timeFrame: Up to 240 hours post single dose
measure: Unbound AUClast (AUClast,u) of TNO155
timeFrame: Up to 240 hours post single dose
measure: Unbound AUCinf (AUCinf,u) of TNO155
timeFrame: Up to 240 hours post single dose
measure: Unbound CL/F (CL/F,u) of TNO155
timeFrame: Up to 240 hours post single dose
measure: Renal clearance (CLr) of TNO155
timeFrame: Up to 240 hours post single dose
measure: Apparent non-renal clearance (CLNR/F) of TNO155
timeFrame: Up to 240 hours post single dose
measure: Fraction of dose excreted in urine (fe) of TNO155
timeFrame: Up to 240 hours post single dose
Other outcomes:
Locations:
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: