Pharmacokinetic Study of Icenticaftor in Participants With Hepatic Impairment

NCT04587622 | Completed Phase 1 FDA Drug

• 1 other identifier: CQBW251A2104
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 2

Brief Summary

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

Conditions

Hepatic Failure

Keywords

Hepatic impairment; Child-Pugh classification; Icenticaftor; QBW251

Outcome Measures

Primary Outcomes (7)

• Maximum observed icenticaftor plasma concentration (Cmax) after single oral dose

  Icenticaftor plasma concentrations will be determined by a validated liquid chromatography with tandem mass spectrometry (LC-MS/MS) method. Cmax of icenticaftor will be determined with Phoenix WinNonlin (Version 6.4 or higher).

  pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose

• Area under the plasma concentration-time curve from time zero to the last measurable concentration sampling time (AUClast) of icenticaftor after single oral dose

  AUClast of icenticaftor will be determined using non-compartment methods with Phoenix WinNonlin (Version 6.4 or higher). The linear trapezoidal rule will be used for AUClast calculation.

  pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose

• Area under the plasma concentration-time curve from time zero to infinity (AUCinf) of icenticaftor after single oral dose

  AUCinf of icenticaftor will be determined using non-compartment methods with Phoenix WinNonlin (Version 6.4 or higher). The linear trapezoidal rule will be used for AUCinf calculation.

  pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose

• Time to reach maximum icenticaftor plasma concentration (Tmax) after single oral dose

  Icenticaftor plasma concentrations will be determined by a validated liquid chromatography with tandem mass spectrometry (LC-MS/MS) method. Tmax of icenticaftor will be determined with Phoenix WinNonlin (Version 6.4 or higher).

  pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose

• Apparent plasma clearance (CL/F) of icenticaftor after single oral dose

  CL/F of icenticaftor will be determined using non-compartment methods with Phoenix WinNonlin (Version 6.4 or higher).

  pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose

• Apparent volume of distribution during terminal phase (Vz/F) of icenticaftor after single oral dose

  Vz/F of icenticaftor will be determined using non-compartment methods with Phoenix WinNonlin (Version 6.4 or higher).

  pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose

• Elimination half-life (T1/2) of icenticaftor after single oral dose

  T1/2 of icenticaftor will be determined using non-compartment methods with Phoenix WinNonlin (Version 6.4 or higher). Regression analysis of the terminal plasma elimination phase will be used for T1/2 calculation.

  pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose

Secondary Outcomes (5)

• Plasma protein binding free fraction (unbound fraction [fu]) of icenticaftor

  3 hours post-dose

• Cmax of unbound icenticaftor (Cmax,u)

  pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose

• AUClast of unbound icenticaftor (AUClast,u)

  pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose

• AUCinf of unbound icenticaftor (AUCinf,u)

  pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose

• CL/F of unbound icenticaftor (CL/F,u)

  pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose

Study Arms (4)

Group 1 - Healthy subjects with normal hepatic function

EXPERIMENTAL

Healthy subjects with normal hepatic function - Control

Drug: Icenticaftor

Group 2 - Mild Hepatic Impairment

EXPERIMENTAL

Mild hepatic impairment: Child-Pugh A (Score 5-6)

Drug: Icenticaftor

Group 3 - Moderate Hepatic Impairment

EXPERIMENTAL

Moderate hepatic impairment: Child-Pugh B (Score 7-9)

Drug: Icenticaftor

Group 4 - Severe Hepatic Impairment

EXPERIMENTAL

Severe hepatic impairment: Child-Pugh C (Score 10-15)

Drug: Icenticaftor

Interventions

Icenticaftor DRUG

Single oral dose of 300 mg of icenticaftor (QBW251)

Also known as: QBW251

Group 1 - Healthy subjects with normal hepatic function; Group 2 - Mild Hepatic Impairment; Group 3 - Moderate Hepatic Impairment; Group 4 - Severe Hepatic Impairment

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male and non-child bearing potential female participants, 18 to 75 years of age (inclusive) at Screening.
• Participants must weigh at least 50.0 kg and must have a body mass index (BMI) within the range of 18.0 to 38.0 kg/m2, inclusive, at Screening.
• Must be a non-smoker or agree to smoke no more than 5 cigarettes (or equivalent) per day from Screening until the End of Study. Participants must maintain the same smoking status throughout the study (i.e. smoker or non smoker).

You may not qualify if:

• Use of other investigational drugs within 5 half-lives prior to dosing of study treatment, or within 30 days, whichever is longer; or longer if required by local regulations.
• Are taking medications prohibited to be taken with the study treatment
• Known history of, or current clinically significant arrhythmias. Have clinically significant ECG abnormality or history of long-QT syndrome or whose QT interval corrected by Fridericia's formula (QTcF) is prolonged (\> 480 msec) at Screening. Participants having myocardial infarction ≥ 5 years ago are eligible to participate.
• Major gastrointestinal tract surgery such as gastrectomy, gastroenterostomy, or bowel resection.
• Healthy Participants:
• Each participant must match in age (± 10 years), gender, weight (± 15%), and smoking status to participants in Group 2, 3, or 4.
• Seated vital signs must be within the following ranges at Screening and Baseline:
• Body temperature, 35.0 to 37.5°C, inclusive.
• Systolic blood pressure, 89 to 149 mmHg, inclusive.
• Diastolic blood pressure, 50 to 89 mmHg, inclusive.
• Pulse rate, 40 to 90 bpm, inclusive.
• Participants must be in good health as determined by medical history, physical examination, ECG, and clinical laboratory tests at Screening.
• Liver disease or liver injury as indicated by abnormal liver function tests.
• Chronic infection with HBV or HCV.
• History or presence of impaired renal function.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (2)

Novartis Investigative Site

Miami, Florida, 33014-3616, United States

Location

Novartis Investigative Site

Orlando, Florida, 32809, United States

Location

Related Links

• Results for CQBW251A2104 from the Novartis Clinical Trials Website
• Patient Lay Trial Summary

MeSH Terms

Conditions

Liver Failure

Interventions

icenticaftor

Condition Hierarchy (Ancestors)

Hepatic Insufficiency; Liver Diseases; Digestive System Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 29, 2020
• First Posted: October 14, 2020
• Study Start: October 30, 2020
• Primary Completion: September 15, 2022
• Study Completion: September 15, 2022
• Last Updated: June 20, 2024

Record last verified: 2024-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)