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

Novartis

Status and phase: Withdrawn; Phase 1

Conditions: Renal Impairment

Treatments: Drug: TNO155

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT05541159

CTNO155A12105

Details and patient eligibility

About

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

Full 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.

Sex: All

Ages: 18 to 75 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Diagnostic

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

0 participants in 4 patient groups

Group 1

Experimental group

Description:

Healthy control participants with normal renal function

Treatment:

Drug: TNO155

Group 2

Experimental group

Description:

Mild renal impairment

Treatment:

Drug: TNO155

Group 3

Experimental group

Description:

Moderate renal impairment

Treatment:

Drug: TNO155

Group 4

Experimental group

Description:

Severe renal impairment

Treatment:

Drug: TNO155