A Phase 1 Study to Evaluate the Pharmacokinetics of JDQ443 in Participants With Hepatic Impairment Compared to Matched Healthy Control Participants.

Phase 1

Terminated

• Conditions: Small Cell Lung Carcinoma
• Interventions: Drug: JDQ443

• Registration Number: NCT05329623
• Lead Sponsor: Novartis Pharmaceuticals

Brief Summary

The purpose of this study is to evaluate the effect of hepatic impairment on the systemic pharmacokinetics (PK), safety, and tolerability of JDQ443 in participants with varying degrees of hepatic impairment.

Detailed Description

This is a Phase 1, open-label, single-dose, multi-center, parallel group study to evaluate the PK of oral JDQ443 in participants with mild, moderate, and/or severe hepatic impairment compared to matched healthy control participants.

The study comprises a 28-day Screening period (Days -28 to -2), a baseline evaluation period (Day -1), a single dose administration of 200 mg of JDQ443 (Day 1), and a follow-up period of 4 days (Days 2 to 4) for PK sample collection. All participants should have a post-study safety follow-up contact conducted approximately 30 days after last administration of study treatment. The study will be considered complete once all the participants have finished the required assessments or have dropped out or been lost to follow-up.

A total of up to 48 participants will be enrolled in this study. Approximately 8 participants will be enrolled in each of mild (Child-Pugh A; Group 2), moderate (Child-Pugh B; Group 3), and severe (Child-Pugh C; Group 4) hepatic impairment groups (to have at least six evaluable participants in each group). Each participant in the healthy control group (Group 1) will be matched to one or more evaluable participants with hepatic impairment with respect to age, body weight and sex. All participants will receive a single JDQ443 dose. Upon completion of mild and moderate impairment groups, as well as matching control participants, an interim analysis will be conducted to compare the PK exposure of the two hepatic impaired groups (Groups 2 and 3) to that of the control participants. The interim analysis is to mitigate the potential safety risks in participants with severe hepatic impairment. If the interim analysis results do not show a clinically relevant increase in exposure of JDQ443 and is well tolerated from a safety perspective, then severe hepatic impairment participants may be enrolled. Participants with severe hepatic impairment will be enrolled only after the completion of the interim analysis.

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2022-03-29
• Study First Submitted QC: 2022-04-07
• Study First Posted: 2022-04-15
• Study Start: 2022-05-03
• Primary Completion: 2024-04-07
• Study Completion: 2024-04-07
• Status Verified: 2024-11
• Last Update Submitted: 2024-11-08
• Last Update Posted: 2024-11-11

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 33

Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Normal hepatic function	JDQ443	Matched healthy participants with normal hepatic function
Mild hepatic impairment	JDQ443	Mild hepatic impaired participants with Child-Pugh A (score of 5 to 6)
Moderate hepatic impairment	JDQ443	Moderate hepatic impairment with Child Pugh B (score from 7 to 9)
Severe hepatic impairment	JDQ443	Severe hepatic impairment with Child Pugh C (score from 10 to 15)

Primary Outcome Measures

Name	Time	Method
Terminal Elimination Half-life (T1/2) of JDQ443	Day 1 (Pre-dose), 0.5, 1, 1.5, 2, 3 , 4 , 6 , 8 , 12 , 24 , 36 , 48 and 72 hours post-dose	Blood samples will be collected for pharmacokinetics characterization. T1/2 will be calculated from plasma concentration-time data using non-compartmental methods and summarized using descriptive statistics.
Area Under the Plasma Concentration-time Curve From Time Zero to the Last Quantifiable Concentration (AUClast) of JDQ443	Day 1 (Pre-dose), 0.5, 1, 1.5, 2, 3 , 4 , 6 , 8 , 12 , 24 , 36 , 48 and 72 hours post-dose	Blood samples will be collected for pharmacokinetics characterization. AUClast will be calculated from plasma concentration-time data using non-compartmental methods and summarized using descriptive statistics.
Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUCinf) of JDQ443	Day 1 (Pre-dose), 0.5, 1, 1.5, 2, 3 , 4 , 6 , 8 , 12 , 24 , 36 , 48 and 72 hours post-dose	Blood samples will be collected for pharmacokinetics characterization. AUCinf will be calculated from plasma concentration-time data using non-compartmental methods and summarized using descriptive statistics.
Maximum Observed Plasma Concentration (Cmax) of JDQ443	Day 1 (Pre-dose), 0.5, 1, 1.5, 2, 3 , 4 , 6 , 8 , 12 , 24 , 36 , 48 and 72 hours post-dose	Blood samples will be collected for pharmacokinetics characterization. Cmax will be calculated from plasma concentration-time data using non-compartmental methods and summarized using descriptive statistics.
Apparent Volume of Distribution of JDQ443 during Terminal Phase (Vz/F)	Day 1 (Pre-dose), 0.5, 1, 1.5, 2, 3 , 4 , 6 , 8 , 12 , 24 , 36 , 48 and 72 hours post-dose	Blood samples will be collected for pharmacokinetics characterization. Vz/F will be calculated from plasma concentration-time data using non-compartmental methods and summarized using descriptive statistics.
Area Under the Plasma Concentration-time Curve from Time Zero to time "t" (AUC0-t) of JDQ443	Day 1 (Pre-dose), 0.5, 1, 1.5, 2, 3 , 4 , 6 , 8 , 12 , 24 , 36 , 48 and 72 hours post-dose	Blood samples will be collected for pharmacokinetics characterization. AUC0-t will be calculated from plasma concentration-time data using non-compartmental methods and summarized using descriptive statistics.
Time to Reach the Maximum Concentration of JDQ443 After Drug Administration (Tmax) of JDQ443	Day 1 (Pre-dose), 0.5, 1, 1.5, 2, 3 , 4 , 6 , 8 , 12 , 24 , 36 , 48 and 72 hours post-dose	Blood samples will be collected for pharmacokinetics characterization. Tmax will be calculated from plasma concentration-time data using non-compartmental methods based on the actual time of sample collection and summarized using descriptive statistics
Time of observation prior to the first observation with a measurable concentration (Tlag) of JDQ443	Day 1 (Pre-dose), 0.5, 1, 1.5, 2, 3 , 4 , 6 , 8 , 12 , 24 , 36 , 48 and 72 hours post-dose	Blood samples will be collected for pharmacokinetics characterization. Tlag will be calculated from plasma concentration-time data using non-compartmental methods and summarized using descriptive statistics.
Apparent Total Body Clearance From Plasma (CL/F) of JDQ443 following Drug Administration	Day 1 (Pre-dose), 0.5, 1, 1.5, 2, 3 , 4 , 6 , 8 , 12 , 24 , 36 , 48 and 72 hours post-dose	Blood samples will be collected for pharmacokinetics characterization. CL/F will be calculated from plasma concentration-time data using non-compartmental methods and summarized using descriptive statistics.
Latest pharmacokinetic sampling time with a measurable concentration (Tlast) of JDQ443	Day 1 (Pre-dose), 0.5, 1, 1.5, 2, 3 , 4 , 6 , 8 , 12 , 24 , 36 , 48 and 72 hours post-dose	Blood samples will be collected for pharmacokinetics characterization. Tlast will be calculated from plasma concentration-time data using non-compartmental methods and summarized using descriptive statistics.

Secondary Outcome Measures

Name	Time	Method
Maximum Observed Plasma Concentration (Cmax) of unbound JDQ443	Day 1 (Pre-dose), 0.5, 1, 1.5, 2, 3 , 4 , 6 , 8 , 12 , 24 , 36 , 48 and 72 hours post-dose	Blood samples will be collected for pharmacokinetics characterization. Cmax of unbound drug will be calculated from plasma concentration-time data using non-compartmental methods and summarized using descriptive statistics.
Area Under the Plasma Concentration-time Curve From Time Zero to the Last Quantifiable Concentration (AUClast) of unbound JDQ443	Day 1 (Pre-dose), 0.5, 1, 1.5, 2, 3 , 4 , 6 , 8 , 12 , 24 , 36 , 48 and 72 hours post-dose	Blood samples will be collected for pharmacokinetics characterization. AUClast of unbound drug will be calculated from plasma concentration-time data using non-compartmental methods and summarized using descriptive statistics.
Area Under the Plasma Concentration-time Curve From Time Zero to time "t" (AUC0-t) of unbound JDQ443	Day 1 (Pre-dose), 0.5, 1, 1.5, 2, 3 , 4 , 6 , 8 , 12 , 24 , 36 , 48 and 72 hours post-dose	Blood samples will be collected for pharmacokinetics characterization. AUC0-t of unbound drug will be calculated from plasma concentration-time data using non-compartmental methods and summarized using descriptive statistics.
Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUCinf) of unbound JDQ443	Day 1 (Pre-dose), 0.5, 1, 1.5, 2, 3 , 4 , 6 , 8 , 12 , 24 , 36 , 48 and 72 hours post-dose	Blood samples will be collected for pharmacokinetics characterization. AUCinf of unbound drug will be calculated from plasma concentration-time data using non-compartmental methods and summarized using descriptive statistics.
Apparent Total Body Clearance From Plasma (CL/F) of unbound JDQ443	Day 1 (Pre-dose), 0.5, 1, 1.5, 2, 3 , 4 , 6 , 8 , 12 , 24 , 36 , 48 and 72 hours post-dose	Blood samples will be collected for pharmacokinetics characterization. CL/F of unbound drug will be calculated from plasma concentration-time data using non-compartmental methods and summarized using descriptive statistics.

Trial Locations

Locations (2)

Orlando Clinical Research Center; 🇺🇸 Orlando, Florida, United States

Texas Liver Institute; 🇺🇸 San Antonio, Texas, United States