A Study to Investigate the Pharmacokinetics and Safety of PKN605 in Participants With Moderate and Severe Renal Impairment Compared to Matched Control Subjects With Normal Renal Function

A Phase 1, Single-dose, Open-label Study to Investigate the Pharmacokinetics and Safety of PKN605 in Participants With Moderate and Severe Renal Impairment Compared to Matched Control Healthy Participants With Normal Renal Function

The purpose of this trial is to assess any potential exposure increases of PKN605 in participants with reduced renal function to support decisions on participant eligibility and dosing in subsequent clinical trials of PKN605.

Study Overview

• Status: Not yet recruiting
• Conditions: Participants With Moderate and Severe Renal Impairment and Healthy Participants
• Intervention / Treatment: Drug: PKN605

Detailed Description

This is a Phase 1, single-dose, open-label, non-randomized renal impairment study to assess the PK after a single administration of PKN605 in participants with moderate (Group 1) and severe (Group 2) renal impairment and matched healthy participants with normal renal function (Group 3).

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Novartis Pharmaceuticals; Phone Number: 1-888-669-6682
• Study Contact Backup: Name: Novartis Pharmaceuticals; Phone Number: +41613241111; Email: novartis.email@novartis.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

All participants (Group 1, 2 & 3)

• Male and female participants 18 to 80 years of age (inclusive).
• Weigh at least 50 kg with a body mass index (BMI) within the range of 18 to 42.0 kg/m2, inclusive, at Screening.

Participants with moderate and severe RI (Group 1 & 2)

• Have impaired renal function as determined by the mean eGFR calculated using the CKD EPI Creatinine - Cystatin C equation (2021) (refer to Section 8.5.1 for equation), and fall into one of the following groups:
• Group 1: moderate RI; eGFR 30 to 60 mL/min, inclusive.
• Group 2: severe RI; eGFR <30 mL/min, not requiring dialysis.
• *The mean eGFR will be calculated from 2 values: one obtained at Screening and a second obtained at least 72 hours later, either at Screening or at the Baseline visit. The mean of these 2 values will be used to assign the renal impairment group.
• Have stable renal function with no clinically significant change (no change ≥25% from Screening 1 to Screening 2 or Baseline value) in renal status prior to first dosing of study treatment as determined by the Investigator and is not currently or has not been previously on hemodialysis for at least 1 year.

Healthy control participants (Group 3)

• Each healthy participant must match the age (±10 years), body weight (±15%), and sex of an individual participant in Group 1 and/or Group 2.
• Has normal renal function with eGFR ≥90 mL/min, determined using the CKD-EPI Creatinine - Cystatin C equation (2021) at Screening.

Exclusion Criteria:

All participants (Group 1, 2 & 3)

• Women of childbearing potential (as defined in the protocol) need to use an effective contraception method during the course of this trial.
• History or current diagnosis of ECG or cardiac abnormalities indicating significant risk of safety for participants such as:
• Clinically significant ECG abnormalities that, in the opinion of the Investigator, would place the participant at increased risk.
• Concomitant clinically significant cardiac arrhythmias, e.g., sustained ventricular tachycardia, and clinically significant second or third degree atrioventricular block without a pacemaker.
• History of long QT syndrome or known family history of ventricular arrhythmia or sudden cardiac death.
• QT interval corrected by Fridericia's formula (QTcF) >450 milliseconds (ms) for males and >460 ms for females, unless considered not clinically significant and not associated with increased arrhythmic risk by the Investigator, with appropriate safety oversight; QTcF must not exceed 470 ms in males and 480 ms in females.
• Use of agents known to prolong the QT interval unless they can be discontinued for the duration of study.
• Initiation or dose adjustment within <4 weeks of screening of medications known to cause acute changes in eGFR (e.g., angiotensin-converting-enzyme [ACE] inhibitors, angiotensin II receptor blockers [ARBs], sodium/glucose cotransporter 2 [SGLT2] inhibitors, diuretics, nonsteroidal anti-inflammatory drugs [NSAIDs]). Note: NSAIDs are excluded for use in participants with moderate and severe renal impairment (refer to Exclusion criterion 23).
• Renal transplant recipients or has had a nephrectomy. Participants with moderate and severe RI (Group 1 & 2)
• Participants requiring dialysis.
• Participants taking erythropoiesis-stimulating agents (ESAs) within the last 6 months of Screening and until end of study (EoS) visit.

Healthy control participants (Group 3)

• History or presence of impaired renal function as indicated by clinically significantly abnormal creatinine or blood urea nitrogen and/or urea values, or abnormal urinary constituents or eGFR <90 mL/min in medical history or at Screening.

Other protocol-defined inclusion/exclusion criteria may apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group 1; PKN605 in participants with moderate renal impairment	Drug: PKN605; PKN605 orally as a tablet under fasted conditions
Experimental: Group 2; PKN605 in participants with severe renal impairment	Drug: PKN605; PKN605 orally as a tablet under fasted conditions
Experimental: Group 3; PKN605 in healthy participants with normal renal function	Drug: PKN605; PKN605 orally as a tablet under fasted conditions

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Primary plasma PK parameters: Cmax	Cmax: The maximum (peak) observed plasma concentration	Up to 5 days
Primary plasma PK parameters: AUClast	AUClast: The AUC from time zero to the last measurable concentration sampling time (Tlast)	Up to 5 days
Primary plasma PK parameters: AUCinf	AUCinf: The AUC from time zero to infinity	Up to 5 days
Secondary plasma PK parameters: Tmax	Tmax: The time to reach maximum (peak) plasma concentration	Up to 5 days
Secondary plasma PK parameters: AUC0-t	AUC0-t: The AUC from time zero to time t	Up to 5 days
Secondary plasma PK parameters: T1/2	T1/2: The elimination half-life associated with the terminal slope (λz) of a semi-logarithmic concentration-time curve (time)	Up to 5 days
Secondary plasma PK parameters: Tlast	Tlast: The last measurable concentration sampling time	Up to 5 days
Secondary plasma PK parameters: CL/F	CL/F: The apparent total body clearance of drug from the plasma	Up to 5 days
Secondary plasma PK parameters: Vz/F	Vz/F: The apparent volume of distribution during terminal phase (associated with λz)	Up to 5 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with Adverse Events (AEs)	Number of participants with Adverse Events (AEs), including abnormal vital signs, electrocardiograms (ECGs) and safety laboratory parameters	Up to 35 days

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals
• Investigators: Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Estimated): September 1, 2026
• Primary Completion (Estimated): February 18, 2027
• Study Completion (Estimated): February 18, 2027

Study Registration Dates

• First Submitted: August 26, 2026
• First Submitted That Met QC Criteria: August 26, 2026
• First Posted (Actual): September 1, 2026

Study Record Updates

• Last Update Posted (Actual): September 1, 2026
• Last Update Submitted That Met QC Criteria: August 26, 2026
• Last Verified: August 1, 2026

More Information

Terms related to this study

• Keywords: tolerability; safety; PK; renal impairment; PKN605
• Additional Relevant MeSH Terms: Urogenital Diseases; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Renal Insufficiency
• Other Study ID Numbers: CPKN605A02104

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No