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.
Panoramica dello studio
Stato
Intervento / Trattamento
Descrizione dettagliata
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).
Tipo di studio
Iscrizione (Stimato)
Fase
- Fase 1
Contatti e Sedi
Contatto studio
- Nome: Novartis Pharmaceuticals
- Numero di telefono: 1-888-669-6682
- Email: novartis.email@novartis.com
Backup dei contatti dello studio
- Nome: Novartis Pharmaceuticals
Luoghi di studio
-
-
Florida
-
Miami, Florida, Stati Uniti, 33136
- Reclutamento
- University of Miami
-
Contatto:
- Dyal Garg
- Numero di telefono: +1 305 355 5111
- Email: dgarg8838@aol.com
-
Investigatore principale:
- Richard A Preston
-
Orlando, Florida, Stati Uniti, 32809
- Reclutamento
- Orlando Clinical Research Center Inc
-
Investigatore principale:
- Thomas C Marbury
-
Contatto:
- Cindy Brown
- Email: cbrown@ocrc.net
-
Tampa, Florida, Stati Uniti, 33614
- Reclutamento
- Genesis Clinical Research
-
Investigatore principale:
- Jesus Navarro
-
Contatto:
- Lauren Navarro
- Email: lnavarro@genesistrials.com
-
-
Criteri di partecipazione
Criteri di ammissibilità
Età idonea allo studio
Accetta volontari sani
Sessi ammissibili allo studio
Descrizione
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
Piano di studio
Come è strutturato lo studio?
Dettagli di progettazione
- Scopo principale: Trattamento
- Assegnazione: Non randomizzato
- Modello interventistico: Assegnazione parallela
- Mascheramento: Nessuno (etichetta aperta)
Armi e interventi
Gruppo di partecipanti / Arm |
Intervento / Trattamento |
|---|---|
|
Sperimentale: Group 1
PKN605 in participants with moderate renal impairment |
PKN605 orally as a tablet under fasted conditions |
|
Sperimentale: Group 2
PKN605 in participants with severe renal impairment |
PKN605 orally as a tablet under fasted conditions |
|
Sperimentale: Group 3
PKN605 in healthy participants with normal renal function |
PKN605 orally as a tablet under fasted conditions |
Cosa sta misurando lo studio?
Misure di risultato primarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
|---|---|---|
|
Primary plasma PK parameters: Cmax
Lasso di tempo: Up to 5 days
|
Cmax: The maximum (peak) observed plasma concentration |
Up to 5 days
|
|
Primary plasma PK parameters: AUClast
Lasso di tempo: Up to 5 days
|
AUClast: The AUC from time zero to the last measurable concentration sampling time (Tlast) |
Up to 5 days
|
|
Primary plasma PK parameters: AUCinf
Lasso di tempo: Up to 5 days
|
AUCinf: The AUC from time zero to infinity |
Up to 5 days
|
|
Secondary plasma PK parameters: Tmax
Lasso di tempo: Up to 5 days
|
Tmax: The time to reach maximum (peak) plasma concentration |
Up to 5 days
|
|
Secondary plasma PK parameters: AUC0-t
Lasso di tempo: Up to 5 days
|
AUC0-t: The AUC from time zero to time t |
Up to 5 days
|
|
Secondary plasma PK parameters: T1/2
Lasso di tempo: Up to 5 days
|
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
Lasso di tempo: Up to 5 days
|
Tlast: The last measurable concentration sampling time |
Up to 5 days
|
|
Secondary plasma PK parameters: CL/F
Lasso di tempo: Up to 5 days
|
CL/F: The apparent total body clearance of drug from the plasma |
Up to 5 days
|
|
Secondary plasma PK parameters: Vz/F
Lasso di tempo: Up to 5 days
|
Vz/F: The apparent volume of distribution during terminal phase (associated with λz) |
Up to 5 days
|
Misure di risultato secondarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
|---|---|---|
|
Number of participants with Adverse Events (AEs)
Lasso di tempo: Up to 35 days
|
Number of participants with Adverse Events (AEs), including abnormal vital signs, electrocardiograms (ECGs) and safety laboratory parameters |
Up to 35 days
|
Collaboratori e investigatori
Sponsor
Investigatori
- Direttore dello studio: Novartis Pharmaceuticals, Novartis Pharmaceuticals
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Inizio studio (Effettivo)
Completamento primario (Stimato)
Completamento dello studio (Stimato)
Date di iscrizione allo studio
Primo inviato
Primo inviato che soddisfa i criteri di controllo qualità
Primo Inserito (Effettivo)
Aggiornamenti dei record di studio
Ultimo aggiornamento pubblicato (Effettivo)
Ultimo aggiornamento inviato che soddisfa i criteri QC
Ultimo verificato
Maggiori informazioni
Termini relativi a questo studio
Parole chiave
Termini MeSH pertinenti aggiuntivi
Altri numeri di identificazione dello studio
- CPKN605A02104
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