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

Studies

Study First Submitted Date 2022-09-12
Study First Posted Date 2022-09-15
Last Update Posted Date 2023-07-28
Start Month Year February 15, 2024
Primary Completion Month Year June 12, 2024
Verification Month Year July 2023
Verification Date 2023-07-31
Last Update Posted Date 2023-07-28

Detailed Descriptions

Sequence: 20849337
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.

Conditions

Sequence: 52499510
Name Renal Impairment
Downcase Name renal impairment

Id Information

Sequence: 40393388
Id Source org_study_id
Id Value CTNO155A12105

Design Groups

Sequence: 55955608 Sequence: 55955609 Sequence: 55955610 Sequence: 55955611
Group Type Experimental Group Type Experimental Group Type Experimental Group Type Experimental
Title Group 1 Title Group 2 Title Group 3 Title Group 4
Description Healthy control participants with normal renal function Description Mild renal impairment Description Moderate renal impairment Description Severe renal impairment

Interventions

Sequence: 52807662
Intervention Type Drug
Name TNO155
Description Single oral dose of TNO155 on Day 1

Keywords

Sequence: 80313823 Sequence: 80313824 Sequence: 80313825
Name TNO155 Name renal Impairment Name SHP2
Downcase Name tno155 Downcase Name renal impairment Downcase Name shp2

Design Outcomes

Sequence: 178605182 Sequence: 178605183 Sequence: 178605184 Sequence: 178605185 Sequence: 178605186 Sequence: 178605187 Sequence: 178605188 Sequence: 178605189 Sequence: 178605190 Sequence: 178605191 Sequence: 178605192 Sequence: 178605193 Sequence: 178605194 Sequence: 178605195 Sequence: 178605196 Sequence: 178605197 Sequence: 178605198
Outcome Type primary Outcome Type primary Outcome Type primary Outcome Type primary Outcome Type primary Outcome Type primary Outcome Type primary Outcome Type primary Outcome Type primary Outcome Type secondary Outcome Type secondary Outcome Type secondary Outcome Type secondary Outcome Type secondary Outcome Type secondary Outcome Type secondary Outcome Type secondary
Measure Area under the concentration-versus-time curve (AUC) from time zero to the last measurable plasma concentration (AUClast) of TNO155 Measure AUC from time zero to time "t" (AUC0-t) of TNO155 Measure AUC from time zero to infinity (AUCinf) of TNO155 Measure Maximum (peak) observed plasma concentration (Cmax) of TNO155 Measure Time to reach maximum observed plasma concentration (Tmax) of TNO155 Measure Elimination half-life (T1/2) of TNO155 Measure Sampling time of the last measurable plasma concentration (Tlast) of TNO155 Measure Apparent plasma clearance (CL/F) of TNO155 Measure Apparent volume of distribution during terminal phase (Vz/F) of TNO155 Measure Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs) Measure Unbound Cmax (Cmax,u) of TNO155 Measure Unbound AUClast (AUClast,u) of TNO155 Measure Unbound AUCinf (AUCinf,u) of TNO155 Measure Unbound CL/F (CL/F,u) of TNO155 Measure Renal clearance (CLr) of TNO155 Measure Apparent non-renal clearance (CLNR/F) of TNO155 Measure Fraction of dose excreted in urine (fe) of TNO155
Time Frame Up to 240 hours post single dose Time Frame AUC from time zero to time "t" (AUC0-t) of TNO155 Time Frame Up to 240 hours post single dose Time Frame Up to 240 hours post single dose Time Frame Up to 240 hours post single dose Time Frame Up to 240 hours post single dose Time Frame Up to 240 hours post single dose Time Frame Up to 240 hours post single dose Time Frame Up to 240 hours post single dose Time Frame Up to 30 days post single dose Time Frame Up to 240 hours post single dose Time Frame Up to 240 hours post single dose Time Frame Up to 240 hours post single dose Time Frame Up to 240 hours post single dose Time Frame Up to 240 hours post single dose Time Frame Up to 240 hours post single dose Time Frame Up to 240 hours post single dose
Description AUClast will be calculated based on TNO155 plasma concentrations and non-compartmental methods. Description 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. Description AUCinf will be calculated based on TNO155 plasma concentrations and non-compartmental methods. Description Cmax will be calculated based on TNO155 plasma concentrations and non-compartmental methods. Description Tmax will be calculated based on TNO155 plasma concentrations and non-compartmental methods Description T1/2 will be calculated based on TNO155 plasma concentrations and non-compartmental methods. Description Tlast will be calculated based on TNO155 plasma concentrations and non-compartmental methods. Description CL/F will be calculated based on TNO155 plasma concentrations and non-compartmental methods. Description Vz/F will be calculated based on TNO155 plasma concentrations and non-compartmental methods. Description Incidence of AEs and SAEs, including changes in vital signs, electrocardiograms (ECGs) and laboratory results qualifying and reported as AEs. Description Cmax,u will be calculated based on the unbound fraction of TNO155 in plasma. Description AUClast,u will be calculated based on the unbound fraction of TNO155 in plasma. Description AUCinf,u will be calculated based on the unbound fraction of TNO155 in plasma Description CL/F,u will be calculated based on the unbound fraction of TNO155 in plasma. Description CLr will be calculated based on urinary excretion data of TNO155. Description CLNR/F will be calculated based on urinary excretion data of TNO155. Description Fe will be calculated based on urinary excretion data of TNO155.

Browse Conditions

Sequence: 194739357 Sequence: 194739358 Sequence: 194739359 Sequence: 194739360 Sequence: 194739361 Sequence: 194739362 Sequence: 194739363
Mesh Term Renal Insufficiency Mesh Term Kidney Diseases Mesh Term Urologic Diseases Mesh Term Female Urogenital Diseases Mesh Term Female Urogenital Diseases and Pregnancy Complications Mesh Term Urogenital Diseases Mesh Term Male Urogenital Diseases
Downcase Mesh Term renal insufficiency Downcase Mesh Term kidney diseases Downcase Mesh Term urologic diseases Downcase Mesh Term female urogenital diseases Downcase Mesh Term female urogenital diseases and pregnancy complications Downcase Mesh Term urogenital diseases Downcase Mesh Term male urogenital diseases
Mesh Type mesh-list Mesh Type mesh-ancestor Mesh Type mesh-ancestor Mesh Type mesh-ancestor Mesh Type mesh-ancestor Mesh Type mesh-ancestor Mesh Type mesh-ancestor

Sponsors

Sequence: 48623586 Sequence: 48623587
Agency Class INDUSTRY Agency Class OTHER
Lead Or Collaborator lead Lead Or Collaborator collaborator
Name Novartis Pharmaceuticals Name Pharmaceutical Research Associates

Overall Officials

Sequence: 29456726
Role Study Director
Name Novartis Pharmaceuticals
Affiliation Novartis Pharmaceuticals

Central Contacts

Sequence: 12093579 Sequence: 12093580
Contact Type primary Contact Type backup
Name Novartis Pharmaceuticals Name Novartis Pharmaceuticals
Phone 1-888-669-6682
Email novartis.email@novartis.com
Role Contact Role Contact

Design Group Interventions

Sequence: 68596492 Sequence: 68596493 Sequence: 68596494 Sequence: 68596495
Design Group Id 55955608 Design Group Id 55955609 Design Group Id 55955610 Design Group Id 55955611
Intervention Id 52807662 Intervention Id 52807662 Intervention Id 52807662 Intervention Id 52807662

Eligibilities

Sequence: 30952757
Gender All
Minimum Age 18 Years
Maximum Age 75 Years
Healthy Volunteers Accepts Healthy Volunteers
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
Adult True
Child False
Older Adult True

Calculated Values

Sequence: 253876507
Registered In Calendar Year 2022
Were Results Reported False
Has Single Facility False
Minimum Age Num 18
Maximum Age Num 75
Minimum Age Unit Years
Maximum Age Unit Years
Number Of Primary Outcomes To Measure 9
Number Of Secondary Outcomes To Measure 8

Designs

Sequence: 30698341
Allocation Non-Randomized
Intervention Model Parallel Assignment
Observational Model
Primary Purpose Diagnostic
Time Perspective
Masking None (Open Label)
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.

Responsible Parties

Sequence: 29065102
Responsible Party Type Sponsor