A Phase 1 Study to Evaluate the Pharmacokinetics of JDQ443 in Participants With Hepatic Impairment Compared to Matched Healthy Control Participants.
Primary Purpose
Small Cell Lung Carcinoma
Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
JDQ443
Sponsored by
About this trial
This is an interventional treatment trial for Small Cell Lung Carcinoma focused on measuring JDQ443, pharmacokinetics, Child-Pugh classification, hepatic impairment
Eligibility Criteria
Key inclusion Criteria:
- Written informed consent must be obtained before any assessment is performed.
- Participants must weigh at least 50.0 kg to participate in the study and must have a body mass index (BMI) within the range of 18 to 40 kg/m2.
- Ability to communicate well with the investigator, to understand and comply with the requirements of the study.
- Participant must be willing to remain in the clinical research unit as required by the protocol.
Key exclusion Criteria:
- Use of other investigational drugs within the last 30 days or 5 half-lives prior to dosing, whichever is longer.
- Use of drugs (prescription, non-prescription and herbal remedies such as St John's wort) known to affect cytochrome p (CYP)3A, including both strong and moderate inhibitors and inducers, within 2 weeks prior to dosing until completion of the EOS Visit.
- Contradiction or hypersensitivity to the investigational compound/compound class or its excipients being used in this study.
- Pregnant or nursing (lactating) women. Pregnancy is defined as the state of a female after conception and until termination of gestation, confirmed by a positive human chorionic gonadotropin (hCG) laboratory test.
- Known history of, or current clinically significant arrhythmias, history of prolonged QT correction formula (QTcF) interval or QTcF >480 msec
Other inclusion/exclusion criteria may apply
Sites / Locations
- Orlando Clinical Research CenterRecruiting
- Texas Liver InstituteRecruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Experimental
Experimental
Experimental
Experimental
Arm Label
Normal hepatic function
Mild hepatic impairment
Moderate hepatic impairment
Severe hepatic impairment
Arm Description
Matched healthy participants with normal hepatic function
Mild hepatic impaired participants with Child-Pugh A (score of 5 to 6)
Moderate hepatic impairment with Child Pugh B (score from 7 to 9)
Severe hepatic impairment with Child Pugh C (score from 10 to 15)
Outcomes
Primary Outcome Measures
Area Under the Plasma Concentration-time Curve From Time Zero to the Last Quantifiable Concentration (AUClast) of JDQ443
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
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
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.
Time to Reach the Maximum Concentration of JDQ443 After Drug Administration (Tmax) of JDQ443
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
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.
Terminal Elimination Half-life (T1/2) of JDQ443
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.
Apparent Total Body Clearance From Plasma (CL/F) of JDQ443 following Drug Administration
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.
Apparent Volume of Distribution of JDQ443 during Terminal Phase (Vz/F)
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
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.
Latest pharmacokinetic sampling time with a measurable concentration (Tlast) of JDQ443
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
Maximum Observed Plasma Concentration (Cmax) of unbound JDQ443
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
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 Infinity (AUCinf) of unbound JDQ443
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.
Area Under the Plasma Concentration-time Curve From Time Zero to time "t" (AUC0-t) of unbound JDQ443
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.
Apparent Total Body Clearance From Plasma (CL/F) of unbound JDQ443
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.
Full Information
NCT ID
NCT05329623
First Posted
March 29, 2022
Last Updated
October 20, 2023
Sponsor
Novartis Pharmaceuticals
1. Study Identification
Unique Protocol Identification Number
NCT05329623
Brief Title
A Phase 1 Study to Evaluate the Pharmacokinetics of JDQ443 in Participants With Hepatic Impairment Compared to Matched Healthy Control Participants.
Official Title
A Phase 1, Open-label, Single-dose, Multi-center, Parallel Group Study to Evaluate the Pharmacokinetics of JDQ443 in Participants With Mild, Moderate or Severe Hepatic Impairment Compared to Matched Healthy Control Participants.
Study Type
Interventional
2. Study Status
Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
May 3, 2022 (Actual)
Primary Completion Date
April 30, 2024 (Anticipated)
Study Completion Date
April 30, 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novartis Pharmaceuticals
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Small Cell Lung Carcinoma
Keywords
JDQ443, pharmacokinetics, Child-Pugh classification, hepatic impairment
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
48 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Normal hepatic function
Arm Type
Experimental
Arm Description
Matched healthy participants with normal hepatic function
Arm Title
Mild hepatic impairment
Arm Type
Experimental
Arm Description
Mild hepatic impaired participants with Child-Pugh A (score of 5 to 6)
Arm Title
Moderate hepatic impairment
Arm Type
Experimental
Arm Description
Moderate hepatic impairment with Child Pugh B (score from 7 to 9)
Arm Title
Severe hepatic impairment
Arm Type
Experimental
Arm Description
Severe hepatic impairment with Child Pugh C (score from 10 to 15)
Intervention Type
Drug
Intervention Name(s)
JDQ443
Intervention Description
All the participants will receive a single oral dose of JDQ443.
Primary Outcome Measure Information:
Title
Area Under the Plasma Concentration-time Curve From Time Zero to the Last Quantifiable Concentration (AUClast) of JDQ443
Description
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.
Time Frame
Day 1 (Pre-dose), 0.5, 1, 1.5, 2, 3 , 4 , 6 , 8 , 12 , 24 , 36 , 48 and 72 hours post-dose
Title
Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUCinf) of JDQ443
Description
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.
Time Frame
Day 1 (Pre-dose), 0.5, 1, 1.5, 2, 3 , 4 , 6 , 8 , 12 , 24 , 36 , 48 and 72 hours post-dose
Title
Maximum Observed Plasma Concentration (Cmax) of JDQ443
Description
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.
Time Frame
Day 1 (Pre-dose), 0.5, 1, 1.5, 2, 3 , 4 , 6 , 8 , 12 , 24 , 36 , 48 and 72 hours post-dose
Title
Time to Reach the Maximum Concentration of JDQ443 After Drug Administration (Tmax) of JDQ443
Description
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 Frame
Day 1 (Pre-dose), 0.5, 1, 1.5, 2, 3 , 4 , 6 , 8 , 12 , 24 , 36 , 48 and 72 hours post-dose
Title
Time of observation prior to the first observation with a measurable concentration (Tlag) of JDQ443
Description
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.
Time Frame
Day 1 (Pre-dose), 0.5, 1, 1.5, 2, 3 , 4 , 6 , 8 , 12 , 24 , 36 , 48 and 72 hours post-dose
Title
Terminal Elimination Half-life (T1/2) of JDQ443
Description
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.
Time Frame
Day 1 (Pre-dose), 0.5, 1, 1.5, 2, 3 , 4 , 6 , 8 , 12 , 24 , 36 , 48 and 72 hours post-dose
Title
Apparent Total Body Clearance From Plasma (CL/F) of JDQ443 following Drug Administration
Description
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.
Time Frame
Day 1 (Pre-dose), 0.5, 1, 1.5, 2, 3 , 4 , 6 , 8 , 12 , 24 , 36 , 48 and 72 hours post-dose
Title
Apparent Volume of Distribution of JDQ443 during Terminal Phase (Vz/F)
Description
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.
Time Frame
Day 1 (Pre-dose), 0.5, 1, 1.5, 2, 3 , 4 , 6 , 8 , 12 , 24 , 36 , 48 and 72 hours post-dose
Title
Area Under the Plasma Concentration-time Curve from Time Zero to time "t" (AUC0-t) of JDQ443
Description
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 Frame
Day 1 (Pre-dose), 0.5, 1, 1.5, 2, 3 , 4 , 6 , 8 , 12 , 24 , 36 , 48 and 72 hours post-dose
Title
Latest pharmacokinetic sampling time with a measurable concentration (Tlast) of JDQ443
Description
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.
Time Frame
Day 1 (Pre-dose), 0.5, 1, 1.5, 2, 3 , 4 , 6 , 8 , 12 , 24 , 36 , 48 and 72 hours post-dose
Secondary Outcome Measure Information:
Title
Maximum Observed Plasma Concentration (Cmax) of unbound JDQ443
Description
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.
Time Frame
Day 1 (Pre-dose), 0.5, 1, 1.5, 2, 3 , 4 , 6 , 8 , 12 , 24 , 36 , 48 and 72 hours post-dose
Title
Area Under the Plasma Concentration-time Curve From Time Zero to the Last Quantifiable Concentration (AUClast) of unbound JDQ443
Description
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.
Time Frame
Day 1 (Pre-dose), 0.5, 1, 1.5, 2, 3 , 4 , 6 , 8 , 12 , 24 , 36 , 48 and 72 hours post-dose
Title
Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUCinf) of unbound JDQ443
Description
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.
Time Frame
Day 1 (Pre-dose), 0.5, 1, 1.5, 2, 3 , 4 , 6 , 8 , 12 , 24 , 36 , 48 and 72 hours post-dose
Title
Area Under the Plasma Concentration-time Curve From Time Zero to time "t" (AUC0-t) of unbound JDQ443
Description
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.
Time Frame
Day 1 (Pre-dose), 0.5, 1, 1.5, 2, 3 , 4 , 6 , 8 , 12 , 24 , 36 , 48 and 72 hours post-dose
Title
Apparent Total Body Clearance From Plasma (CL/F) of unbound JDQ443
Description
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.
Time Frame
Day 1 (Pre-dose), 0.5, 1, 1.5, 2, 3 , 4 , 6 , 8 , 12 , 24 , 36 , 48 and 72 hours post-dose
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Key inclusion Criteria:
Written informed consent must be obtained before any assessment is performed.
Participants must weigh at least 50.0 kg to participate in the study and must have a body mass index (BMI) within the range of 18 to 40 kg/m2.
Ability to communicate well with the investigator, to understand and comply with the requirements of the study.
Participant must be willing to remain in the clinical research unit as required by the protocol.
Key exclusion Criteria:
Use of other investigational drugs within the last 30 days or 5 half-lives prior to dosing, whichever is longer.
Use of drugs (prescription, non-prescription and herbal remedies such as St John's wort) known to affect cytochrome p (CYP)3A, including both strong and moderate inhibitors and inducers, within 2 weeks prior to dosing until completion of the EOS Visit.
Contradiction or hypersensitivity to the investigational compound/compound class or its excipients being used in this study.
Pregnant or nursing (lactating) women. Pregnancy is defined as the state of a female after conception and until termination of gestation, confirmed by a positive human chorionic gonadotropin (hCG) laboratory test.
Known history of, or current clinically significant arrhythmias, history of prolonged QT correction formula (QTcF) interval or QTcF >480 msec
Other inclusion/exclusion criteria may apply
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Novartis Pharmaceuticals
Phone
1-888-669-6682
Email
novartis.email@novartis.com
First Name & Middle Initial & Last Name or Official Title & Degree
Novartis Pharmaceuticals
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Novartis Pharmaceuticals
Organizational Affiliation
Novartis Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
Orlando Clinical Research Center
City
Orlando
State/Province
Florida
ZIP/Postal Code
32809
Country
United States
Individual Site Status
Recruiting
Facility Contact:
Phone
407-472-0227
First Name & Middle Initial & Last Name & Degree
Thomas C Marbury
Facility Name
Texas Liver Institute
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78215
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Eric J Lawitz
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
A Phase 1 Study to Evaluate the Pharmacokinetics of JDQ443 in Participants With Hepatic Impairment Compared to Matched Healthy Control Participants.
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