Clinical trial NCT05329623: 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
Overall status: TERMINATED
Phase: PHASE1
Conditions: Small Cell Lung Carcinoma
Keywords: JDQ443
pharmacokinetics
Child-Pugh classification
hepatic impairment
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2022-04-15
Enrollment: 33
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Area Under the Plasma Concentration-time Curve From Time Zero to the Last Quantifiable Concentration (AUClast) of JDQ443
timeFrame: Day 1 (Pre-dose), 0.5, 1, 1.5, 2, 3 , 4 , 6 , 8 , 12 , 24 , 36 , 48 and 72 hours post-dose
measure: Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUCinf) of JDQ443
timeFrame: Day 1 (Pre-dose), 0.5, 1, 1.5, 2, 3 , 4 , 6 , 8 , 12 , 24 , 36 , 48 and 72 hours post-dose
measure: Maximum Observed Plasma Concentration (Cmax) of JDQ443
timeFrame: Day 1 (Pre-dose), 0.5, 1, 1.5, 2, 3 , 4 , 6 , 8 , 12 , 24 , 36 , 48 and 72 hours post-dose
measure: Time to Reach the Maximum Concentration of JDQ443 After Drug Administration (Tmax) of JDQ443
timeFrame: Day 1 (Pre-dose), 0.5, 1, 1.5, 2, 3 , 4 , 6 , 8 , 12 , 24 , 36 , 48 and 72 hours post-dose
measure: Time of observation prior to the first observation with a measurable concentration (Tlag) of JDQ443
timeFrame: Day 1 (Pre-dose), 0.5, 1, 1.5, 2, 3 , 4 , 6 , 8 , 12 , 24 , 36 , 48 and 72 hours post-dose
measure: Terminal Elimination Half-life (T1/2) of JDQ443
timeFrame: Day 1 (Pre-dose), 0.5, 1, 1.5, 2, 3 , 4 , 6 , 8 , 12 , 24 , 36 , 48 and 72 hours post-dose
measure: Apparent Total Body Clearance From Plasma (CL/F) of JDQ443 following Drug Administration
timeFrame: Day 1 (Pre-dose), 0.5, 1, 1.5, 2, 3 , 4 , 6 , 8 , 12 , 24 , 36 , 48 and 72 hours post-dose
measure: Apparent Volume of Distribution of JDQ443 during Terminal Phase (Vz/F)
timeFrame: Day 1 (Pre-dose), 0.5, 1, 1.5, 2, 3 , 4 , 6 , 8 , 12 , 24 , 36 , 48 and 72 hours post-dose
measure: Area Under the Plasma Concentration-time Curve from Time Zero to time "t" (AUC0-t) of JDQ443
timeFrame: Day 1 (Pre-dose), 0.5, 1, 1.5, 2, 3 , 4 , 6 , 8 , 12 , 24 , 36 , 48 and 72 hours post-dose
measure: Latest pharmacokinetic sampling time with a measurable concentration (Tlast) of JDQ443
timeFrame: Day 1 (Pre-dose), 0.5, 1, 1.5, 2, 3 , 4 , 6 , 8 , 12 , 24 , 36 , 48 and 72 hours post-dose
Secondary outcomes:
measure: Maximum Observed Plasma Concentration (Cmax) of unbound JDQ443
timeFrame: Day 1 (Pre-dose), 0.5, 1, 1.5, 2, 3 , 4 , 6 , 8 , 12 , 24 , 36 , 48 and 72 hours post-dose
measure: Area Under the Plasma Concentration-time Curve From Time Zero to the Last Quantifiable Concentration (AUClast) of unbound JDQ443
timeFrame: Day 1 (Pre-dose), 0.5, 1, 1.5, 2, 3 , 4 , 6 , 8 , 12 , 24 , 36 , 48 and 72 hours post-dose
measure: Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUCinf) of unbound JDQ443
timeFrame: Day 1 (Pre-dose), 0.5, 1, 1.5, 2, 3 , 4 , 6 , 8 , 12 , 24 , 36 , 48 and 72 hours post-dose
measure: Area Under the Plasma Concentration-time Curve From Time Zero to time "t" (AUC0-t) of unbound JDQ443
timeFrame: Day 1 (Pre-dose), 0.5, 1, 1.5, 2, 3 , 4 , 6 , 8 , 12 , 24 , 36 , 48 and 72 hours post-dose
measure: Apparent Total Body Clearance From Plasma (CL/F) of unbound JDQ443
timeFrame: Day 1 (Pre-dose), 0.5, 1, 1.5, 2, 3 , 4 , 6 , 8 , 12 , 24 , 36 , 48 and 72 hours post-dose
Other outcomes:
Locations:
city: Orlando
country: United States
facility: Orlando Clinical Research Center
state: Florida
city: San Antonio
country: United States
facility: Texas Liver Institute
state: Texas
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: