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A Study to Evaluate the Pharmacokinetics and Safety of INCB054707 in Participants With Normal Hepatic Function and Participants With Hepatic Impairment

Primary Purpose

Renal Insufficiency, Kidney Diseases

Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
INCB054707
Sponsored by
Incyte Corporation
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Renal Insufficiency focused on measuring renal impairment, hemodialysis, Kidney failure, end-stage renal disease

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria: - Participants with hepatic impairment will be classified at screening based on Child-Pugh score. Classification will be repeated at check-in and should not be significantly different. If the hepatic function classification for the participant is not similar at the 2 timepoints, enrollment of the participant into a hepatic category group will be at the discretion of the investigator, in consultation with the sponsor's medical monitor. The enrollment group will be based on the results at screening. Participants eligible for Group 4 (normal hepatic function) should be in good health as determined by no clinically significant findings in the medical history, physical examination, vital signs, 12-lead ECGs, or laboratory examinations at screening or check-in. Participants eligible for Groups 1 through 3 may have medical findings consistent with their degree of hepatic dysfunction, as determined by medical history, physical examination, vital signs, 12-lead ECGs, and clinical laboratory examinations at screening and check-in. Participants with abnormal findings considered not clinically significant by the investigator are eligible. BMI within the range of 18.0 to 44.0 kg/m2 (inclusive) at screening. Willingness to avoid pregnancy or fathering children. Exclusion Criteria: the opinion of the principal investigator, history of uncontrolled or unstable cardiovascular, respiratory, renal, GI, endocrine, hematopoietic, psychiatric, and/or neurological disease within 6 months of screening or evidence of rapidly deteriorating hepatic function. Serum corrected calcium and phosphorus levels over the upper limits of the institutional normal ranges. History or current diagnosis of uncontrolled or significant cardiac disease indicating significant risk of safety for participation in the study, including any of the following: Recent myocardial infarction (within 6 months of check-in). New York Heart Association Class III or IV congestive heart failure. Unstable angina (within 6 months of check-in). Clinically significant (symptomatic) cardiac arrhythmias (eg, sustained ventricular tachycardia, second or third degree atrioventricular block without a pacemaker). Uncontrolled hypertension. A current, functioning organ transplant or a scheduled organ transplant in the next 6 weeks from check-in. History of malignancy within 5 years of screening, with the exception of cured basal cell carcinoma, squamous cell carcinoma of the skin, ductal carcinoma in situ, or Gleason 6 prostate cancer. History of clinically significant GI disease or surgery (cholecystectomy and appendectomy are allowed) that could impact the absorption of study drug. Severe ascites (ascites requiring paracentesis more than every 4 weeks) or an encephalopathy ≥ Grade 2 (precludes them from understanding and signing an informed consent). Any major surgery within 4 weeks of screening. Donation of blood to a blood bank within 4 weeks of screening (within 2 weeks for plasma only). Blood transfusion within 4 weeks of check-in. Current or recent history (within 30 days before screening) of a clinically significant bacterial, fungal, parasitic, or mycobacterial infection, or currently receiving systemic antibiotics or current clinically significant viral infection at screening or check-in. Positive serology for HBV (eg, HBsAg) or HIV. Participants whose results are compatible with immunity due to infection or prior immunization for HBV may be included at the discretion of the investigator.

Sites / Locations

  • Orange County Research Center
  • Orlando Clinical Research Center
  • Texas Liver Institute Tli the Liver Institute of South Texas List Downtown Office
  • Apex Gmbh

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Experimental

Experimental

Arm Label

Group 1: Severe Hepatic Impairment

Group 2: Moderate Hepatic Impairment

Group 3: Mild Hepatic Impairment

Group D: Normal Hepatic Function

Arm Description

Participants with severe hepatic impairment (Class C Child-Pugh score) will receive a single oral dose of INCB054707 on Day 1.

Participants with moderate hepatic impairment (Class B Child-Pugh score) will receive a single oral dose of INCB054707 on Day 1.

Participants with mild hepatic impairment (Class A Child-Pugh score) will receive a single oral dose of INCB054707 on Day 1.

Participants with normal hepatic function will receive a single oral dose of INCB054707 on Day 1.

Outcomes

Primary Outcome Measures

Pharmacokinetics Parameter: Cmax of INCBC054707
Defined as maximum observed plasma concentration of INCB054707
Pharmacokinetics Parameter: AUC(0-t) of INCB054707
Defined as the area under the concentration- time curve up to the last measurable concentration of INCB54707.
Pharmacokinetics Parameter: AUC(0-∞) of INCB054707
Defined as area under the concentration-time curve From 0 to Infinity of INCB054707

Secondary Outcome Measures

Number of Treatment Emergent Adverse Events (TEAE'S)
Adverse events reported for the first time or worsening of a pre-existing event after first dose of study drug/treatment.
Pharmacokinetics Parameter: tmax of INCB054707
Defined as time to reach maximum plasma concentration of INCB054707
Pharmacokinetics Parameter: t1/2 0f INCB054707
Defined as apparent terminal phase disposition half-life of INCB54707
Pharmacokinetics Parameter: CL/F of INCB054707
Defined as oral dose clearance of INCB054707
Pharmacokinetics Parameter:: Vz/F of INCB054707
Defined as apparent oral dose volume of distribution of INCB054707

Full Information

First Posted
November 11, 2022
Last Updated
August 31, 2023
Sponsor
Incyte Corporation
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1. Study Identification

Unique Protocol Identification Number
NCT05624710
Brief Title
A Study to Evaluate the Pharmacokinetics and Safety of INCB054707 in Participants With Normal Hepatic Function and Participants With Hepatic Impairment
Official Title
A Phase 1, Open-Label Study to Evaluate the Pharmacokinetics and Safety of INCB054707 in Participants With Normal Hepatic Function and Participants With Hepatic Impairment
Study Type
Interventional

2. Study Status

Record Verification Date
August 2023
Overall Recruitment Status
Completed
Study Start Date
December 8, 2022 (Actual)
Primary Completion Date
June 29, 2023 (Actual)
Study Completion Date
June 29, 2023 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Incyte Corporation

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
This is a multicenter, open-label, parallel-group study to evaluate INCB054707 in participants with varying levels of renal function or impairment.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Renal Insufficiency, Kidney Diseases
Keywords
renal impairment, hemodialysis, Kidney failure, end-stage renal disease

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Masking Description
open label study
Allocation
Non-Randomized
Enrollment
25 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Group 1: Severe Hepatic Impairment
Arm Type
Experimental
Arm Description
Participants with severe hepatic impairment (Class C Child-Pugh score) will receive a single oral dose of INCB054707 on Day 1.
Arm Title
Group 2: Moderate Hepatic Impairment
Arm Type
Experimental
Arm Description
Participants with moderate hepatic impairment (Class B Child-Pugh score) will receive a single oral dose of INCB054707 on Day 1.
Arm Title
Group 3: Mild Hepatic Impairment
Arm Type
Experimental
Arm Description
Participants with mild hepatic impairment (Class A Child-Pugh score) will receive a single oral dose of INCB054707 on Day 1.
Arm Title
Group D: Normal Hepatic Function
Arm Type
Experimental
Arm Description
Participants with normal hepatic function will receive a single oral dose of INCB054707 on Day 1.
Intervention Type
Drug
Intervention Name(s)
INCB054707
Other Intervention Name(s)
Povorcitinib
Intervention Description
INCB054707 75 mg will be administered orally on Day 1.
Primary Outcome Measure Information:
Title
Pharmacokinetics Parameter: Cmax of INCBC054707
Description
Defined as maximum observed plasma concentration of INCB054707
Time Frame
Days 1 - 5
Title
Pharmacokinetics Parameter: AUC(0-t) of INCB054707
Description
Defined as the area under the concentration- time curve up to the last measurable concentration of INCB54707.
Time Frame
Days 1 - 5
Title
Pharmacokinetics Parameter: AUC(0-∞) of INCB054707
Description
Defined as area under the concentration-time curve From 0 to Infinity of INCB054707
Time Frame
Days 1 - 5
Secondary Outcome Measure Information:
Title
Number of Treatment Emergent Adverse Events (TEAE'S)
Description
Adverse events reported for the first time or worsening of a pre-existing event after first dose of study drug/treatment.
Time Frame
up to 15 days
Title
Pharmacokinetics Parameter: tmax of INCB054707
Description
Defined as time to reach maximum plasma concentration of INCB054707
Time Frame
Days 1 - 5
Title
Pharmacokinetics Parameter: t1/2 0f INCB054707
Description
Defined as apparent terminal phase disposition half-life of INCB54707
Time Frame
Days 1 - 5
Title
Pharmacokinetics Parameter: CL/F of INCB054707
Description
Defined as oral dose clearance of INCB054707
Time Frame
Days 1 - 5
Title
Pharmacokinetics Parameter:: Vz/F of INCB054707
Description
Defined as apparent oral dose volume of distribution of INCB054707
Time Frame
Days 1 - 5

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: - Participants with hepatic impairment will be classified at screening based on Child-Pugh score. Classification will be repeated at check-in and should not be significantly different. If the hepatic function classification for the participant is not similar at the 2 timepoints, enrollment of the participant into a hepatic category group will be at the discretion of the investigator, in consultation with the sponsor's medical monitor. The enrollment group will be based on the results at screening. Participants eligible for Group 4 (normal hepatic function) should be in good health as determined by no clinically significant findings in the medical history, physical examination, vital signs, 12-lead ECGs, or laboratory examinations at screening or check-in. Participants eligible for Groups 1 through 3 may have medical findings consistent with their degree of hepatic dysfunction, as determined by medical history, physical examination, vital signs, 12-lead ECGs, and clinical laboratory examinations at screening and check-in. Participants with abnormal findings considered not clinically significant by the investigator are eligible. BMI within the range of 18.0 to 44.0 kg/m2 (inclusive) at screening. Willingness to avoid pregnancy or fathering children. Exclusion Criteria: the opinion of the principal investigator, history of uncontrolled or unstable cardiovascular, respiratory, renal, GI, endocrine, hematopoietic, psychiatric, and/or neurological disease within 6 months of screening or evidence of rapidly deteriorating hepatic function. Serum corrected calcium and phosphorus levels over the upper limits of the institutional normal ranges. History or current diagnosis of uncontrolled or significant cardiac disease indicating significant risk of safety for participation in the study, including any of the following: Recent myocardial infarction (within 6 months of check-in). New York Heart Association Class III or IV congestive heart failure. Unstable angina (within 6 months of check-in). Clinically significant (symptomatic) cardiac arrhythmias (eg, sustained ventricular tachycardia, second or third degree atrioventricular block without a pacemaker). Uncontrolled hypertension. A current, functioning organ transplant or a scheduled organ transplant in the next 6 weeks from check-in. History of malignancy within 5 years of screening, with the exception of cured basal cell carcinoma, squamous cell carcinoma of the skin, ductal carcinoma in situ, or Gleason 6 prostate cancer. History of clinically significant GI disease or surgery (cholecystectomy and appendectomy are allowed) that could impact the absorption of study drug. Severe ascites (ascites requiring paracentesis more than every 4 weeks) or an encephalopathy ≥ Grade 2 (precludes them from understanding and signing an informed consent). Any major surgery within 4 weeks of screening. Donation of blood to a blood bank within 4 weeks of screening (within 2 weeks for plasma only). Blood transfusion within 4 weeks of check-in. Current or recent history (within 30 days before screening) of a clinically significant bacterial, fungal, parasitic, or mycobacterial infection, or currently receiving systemic antibiotics or current clinically significant viral infection at screening or check-in. Positive serology for HBV (eg, HBsAg) or HIV. Participants whose results are compatible with immunity due to infection or prior immunization for HBV may be included at the discretion of the investigator.
Facility Information:
Facility Name
Orange County Research Center
City
Tustin
State/Province
California
ZIP/Postal Code
92780
Country
United States
Facility Name
Orlando Clinical Research Center
City
Orlando
State/Province
Florida
ZIP/Postal Code
32809
Country
United States
Facility Name
Texas Liver Institute Tli the Liver Institute of South Texas List Downtown Office
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78215
Country
United States
Facility Name
Apex Gmbh
City
Munich
ZIP/Postal Code
D-81241
Country
Germany

12. IPD Sharing Statement

Plan to Share IPD
No

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A Study to Evaluate the Pharmacokinetics and Safety of INCB054707 in Participants With Normal Hepatic Function and Participants With Hepatic Impairment

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