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Study to Evaluate the Pharmacokinetics, Safety, and Pharmacodynamics of INCB054707 in Participants With Normal and Impaired Renal Function and Participants on Hemodialysis

Primary Purpose

Renal Insufficiency, Kidney Diseases

Status
Recruiting
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 - 82 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria: Classification at screening by renal function based on eGFR as calculated by the MDRD formula and requirement for HD (Group 5). Participants eligible for Group 5 with ESRD have received HD for at least 3 months prior to screening. Participants eligible for Group 1 should be in good health as determined by no clinically significant deviations from normal for medical history, physical examination, vital signs, 12-lead ECGs, or clinical laboratory determinations at screening or Day -1. Participants eligible for Groups 2 through 5 may have medical findings consistent with their degree of renal dysfunction, as determined by medical history, physical examination, vital signs, 12-lead ECGs, and clinical laboratory determinations at screening and Day -1 (Groups 2 through 4) or Period 1 Day -1 (Group 5). Body mass index within the range of 18.0 to 40.0 kg/m2 (inclusive) at screening. Willingness to avoid pregnancy or fathering children Exclusion Criteria: History of uncontrolled or unstable cardiovascular, respiratory, hepatic, GI, endocrine, hematopoietic, psychiatric, and/or neurological disease within 6 months of screening or evidence of rapidly deteriorating renal function. Current, functioning organ transplant or a cheduled organ transplant within 6 weeks after 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. Eligible for Group 1 and have a history of renal disease or renal injury as indicated by an abnormal, clinically significant renal function profile at screening or Day -1. Eligible for Groups 2 through 5 and have had a change in disease status within 30 days of screening, as documented by the participant's medical history and deemed clinically significant by the investigator. 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 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 Day -1 (for Groups 1 through 4) or Period 1 Day -1 (Group 5). Chronic or current active infectious disease requiring systemic antibiotic, antifungal, or antiviral treatment. Positive test and symptomatic for HBV, HCV, or HIV. Participants whose results are compatible with prior immunization for or immunity due to infection with HBV may be included at the discretion of the investigator. Eligible for Group 1 and have a history of using tobacco- or nicotine-containing products within 6 months of screening. Eligible for Groups 2 through 5 and smoke > 10 cigarettes per day or equivalent use of other tobacco- or nicotine-containing products and are unwilling to refrain from tobacco or nicotine use on dosing days and abide by CRU restrictions. History of alcohol dependency within 3 months of screening. Positive breath test for ethanol or positive urine or saliva screen for drugs of abuse (confirmed by repeat test) at screening or check-in that are not otherwise explained by permitted concomitant medications. Current treatment or treatment within 30 days or 5 half-lives (whichever is longer) of study drug administration with another investigational medication or current enrollment in another investigational drug study. Current treatment or treatment within 15 days or 5 half-lives (whichever is longer) before the first dose of study drug with moderate and potent inducers or inhibitors of CYP3A4 (refer to the Drug Interaction Database Program [University of Washington School of Pharmacy 2002] for prohibited drugs). Consumption of Seville oranges, grapefruit or grapefruit juice, pomelos, exotic citrus fruits, grapefruit hybrids, or fruit juices within 72 hours before the first dose of study drug. Eligible for Group 1 and have used prescription drugs within 14 days of study drug administration or nonprescription medications/products (including vitamins, minerals, and hytotherapeutic/herbal/plant-derived preparations) within 7 days of study drug administration. However, occasional use of acetaminophen and ibuprofen is permitted (see Section 6.6.1). Eligible for Groups 2 through 5 and have used prescription drugs within 14 days of study drug administration, with the exception of established therapy for renal disease and the treatment of associated disorders that have been stable for at least 7 days prior to study drug administration, as approved by the investigator and in consultation with the sponsor's medical monitor. Current or recent history (within 30 days before screening) of a clinically significant bacterial, fungal, parasitic, or mycobacterial infection, currently receiving systemic antibiotics, or having a current clinically significant viral infection at screening or check-in. History of any significant drug allergy (such as anaphylaxis or hepatotoxicity) deemed clinically relevant by the investigator. Inability to undergo venipuncture or tolerate venous access. Eligible for Group 5 and not expected to continue HD treatment for the duration of the study. Women who are pregnant or breastfeeding. Use of hormonal contraception QTcF > 450 milliseconds for Groups 1 through 3 and QTcF > 470 milliseconds for Group 4. Eligible for Group 1 and have abnormal LFT values, defined as aspartate aminotransferase, alanine aminotransferase, and serum (total and direct) bilirubin, as well as amylase and lipase above the upper limit of the normal range at screening. Eligible for Groups 2 through 4 and have values outside the normal ranges for LFTs; however, values may be acceptable if they are consistent with the participant's renal condition (if stable for 1 month prior to screening) and if the investigator (or designee) and the sponsor feel that the results are not clinically significant (based on age and renal impairment status). Receipt of live (including attenuated) vaccines within 3 months of check-in or anticipation of need for such a vaccine during the study (Note: Nonlive or inactivated vaccines are allowed up to 2 weeks prior to the first dose of study drug). Known hypersensitivity or severe reaction to INCB054707 or excipients of INCB054707 (refer to the IB).

Sites / Locations

  • Orlando Clinical Research CenterRecruiting
  • Apex GmbhRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm Type

Experimental

Experimental

Experimental

Experimental

Experimental

Arm Label

Group 1: Normal Renal Function

Group 2: Mild Renal Impairment

Group 3: Moderate Renal Impairment

Group 4: Severe Renal Impairment

Group 5: Kidney Failure

Arm Description

Participants with normal levels of renal function will receive a single oral dose of INCB054707 75 mg on Day 1.

Participants with mild levels of renal function will receive a single oral dose of INCB054707 75 mg on Day 1.

Participants with moderate levels of renal function will receive a single oral dose of INCB054707 75 mg on Day 1.

Participants with severe levels of renal function will receive a single oral dose of INCB054707 75 mg on Day 1.

Group 5 participants with ESRD maintained on HD will receive a single dose of INCB054707 across 2 treatment periods before (Period 1) and after (Period 2) an HD session in order to study the effects of HD on INCB054707.

Outcomes

Primary Outcome Measures

Pharmacokinetics Parameter: Cmax of INCB054707
Defined as maximum observed plasma concentration of INCB054707
Pharmacokinetics Parameter: AUC0-t of INCB054707
Area Under the concentration- time curve up to the last measurable concentration of INCB054707
Pharmacokinetics Parameter: AUC0-∞ of INCB54707
Defined as under the concentration-time curve up to the last measurable concentration 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; during dialysis for Group 5 Period 1.
Pharmacokinetics Parameter: t½ of INCB054707
Defined as apparent terminal-phase disposition half-life of INCB054707; during dialysis for Group 5 Period 1.
Pharmacokinetics Parameter: CL/F of INCB054707
Defined as oral dose clearance of INCB054707; during dialysis for Group 5 Period 1.
Pharmacokinetics Parameter: Vz/F of INCB054707
Defined as apparent oral dose volume of distribution; during dialysis for Group 5 Period 1.
Pharmacokinetics Parameter: AUC3-7 of INCB054707
Defined as area under the concentration-time curve from 1 to 5 of INCB054707; during dialysis for Group 5 Period 1.

Full Information

First Posted
January 12, 2023
Last Updated
February 17, 2023
Sponsor
Incyte Corporation
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1. Study Identification

Unique Protocol Identification Number
NCT05694195
Brief Title
Study to Evaluate the Pharmacokinetics, Safety, and Pharmacodynamics of INCB054707 in Participants With Normal and Impaired Renal Function and Participants on Hemodialysis
Official Title
A Phase 1, Open-label Study to Evaluate the Pharmacokinetics, Safety, and Pharmacodynamics of INCB054707 in Participants With Normal and Impaired Renal Function and Participants on Hemodialysis
Study Type
Interventional

2. Study Status

Record Verification Date
February 2023
Overall Recruitment Status
Recruiting
Study Start Date
January 12, 2023 (Actual)
Primary Completion Date
May 15, 2023 (Anticipated)
Study Completion Date
August 4, 2023 (Anticipated)

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 multi-center, open-label, parallel-group study to evaluate oral doses of 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)
Allocation
Non-Randomized
Enrollment
24 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Group 1: Normal Renal Function
Arm Type
Experimental
Arm Description
Participants with normal levels of renal function will receive a single oral dose of INCB054707 75 mg on Day 1.
Arm Title
Group 2: Mild Renal Impairment
Arm Type
Experimental
Arm Description
Participants with mild levels of renal function will receive a single oral dose of INCB054707 75 mg on Day 1.
Arm Title
Group 3: Moderate Renal Impairment
Arm Type
Experimental
Arm Description
Participants with moderate levels of renal function will receive a single oral dose of INCB054707 75 mg on Day 1.
Arm Title
Group 4: Severe Renal Impairment
Arm Type
Experimental
Arm Description
Participants with severe levels of renal function will receive a single oral dose of INCB054707 75 mg on Day 1.
Arm Title
Group 5: Kidney Failure
Arm Type
Experimental
Arm Description
Group 5 participants with ESRD maintained on HD will receive a single dose of INCB054707 across 2 treatment periods before (Period 1) and after (Period 2) an HD session in order to study the effects of HD on INCB054707.
Intervention Type
Drug
Intervention Name(s)
INCB054707
Other Intervention Name(s)
Povorcitinib
Intervention Description
INCB054707 75 mg will be administered orally
Primary Outcome Measure Information:
Title
Pharmacokinetics Parameter: Cmax of INCB054707
Description
Defined as maximum observed plasma concentration of INCB054707
Time Frame
Days 1-4
Title
Pharmacokinetics Parameter: AUC0-t of INCB054707
Description
Area Under the concentration- time curve up to the last measurable concentration of INCB054707
Time Frame
Days 1-4
Title
Pharmacokinetics Parameter: AUC0-∞ of INCB54707
Description
Defined as under the concentration-time curve up to the last measurable concentration of INCB054707
Time Frame
Days 1-4
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 21 days
Title
Pharmacokinetics Parameter: tmax of INCB054707
Description
Defined as time to reach maximum plasma concentration of INCB054707; during dialysis for Group 5 Period 1.
Time Frame
Days 1-4
Title
Pharmacokinetics Parameter: t½ of INCB054707
Description
Defined as apparent terminal-phase disposition half-life of INCB054707; during dialysis for Group 5 Period 1.
Time Frame
Days 1-4
Title
Pharmacokinetics Parameter: CL/F of INCB054707
Description
Defined as oral dose clearance of INCB054707; during dialysis for Group 5 Period 1.
Time Frame
Days 1-4
Title
Pharmacokinetics Parameter: Vz/F of INCB054707
Description
Defined as apparent oral dose volume of distribution; during dialysis for Group 5 Period 1.
Time Frame
Days 1-4
Title
Pharmacokinetics Parameter: AUC3-7 of INCB054707
Description
Defined as area under the concentration-time curve from 1 to 5 of INCB054707; during dialysis for Group 5 Period 1.
Time Frame
Days 1-4

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
82 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Classification at screening by renal function based on eGFR as calculated by the MDRD formula and requirement for HD (Group 5). Participants eligible for Group 5 with ESRD have received HD for at least 3 months prior to screening. Participants eligible for Group 1 should be in good health as determined by no clinically significant deviations from normal for medical history, physical examination, vital signs, 12-lead ECGs, or clinical laboratory determinations at screening or Day -1. Participants eligible for Groups 2 through 5 may have medical findings consistent with their degree of renal dysfunction, as determined by medical history, physical examination, vital signs, 12-lead ECGs, and clinical laboratory determinations at screening and Day -1 (Groups 2 through 4) or Period 1 Day -1 (Group 5). Body mass index within the range of 18.0 to 40.0 kg/m2 (inclusive) at screening. Willingness to avoid pregnancy or fathering children Exclusion Criteria: History of uncontrolled or unstable cardiovascular, respiratory, hepatic, GI, endocrine, hematopoietic, psychiatric, and/or neurological disease within 6 months of screening or evidence of rapidly deteriorating renal function. Current, functioning organ transplant or a cheduled organ transplant within 6 weeks after 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. Eligible for Group 1 and have a history of renal disease or renal injury as indicated by an abnormal, clinically significant renal function profile at screening or Day -1. Eligible for Groups 2 through 5 and have had a change in disease status within 30 days of screening, as documented by the participant's medical history and deemed clinically significant by the investigator. 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 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 Day -1 (for Groups 1 through 4) or Period 1 Day -1 (Group 5). Chronic or current active infectious disease requiring systemic antibiotic, antifungal, or antiviral treatment. Positive test and symptomatic for HBV, HCV, or HIV. Participants whose results are compatible with prior immunization for or immunity due to infection with HBV may be included at the discretion of the investigator. Eligible for Group 1 and have a history of using tobacco- or nicotine-containing products within 6 months of screening. Eligible for Groups 2 through 5 and smoke > 10 cigarettes per day or equivalent use of other tobacco- or nicotine-containing products and are unwilling to refrain from tobacco or nicotine use on dosing days and abide by CRU restrictions. History of alcohol dependency within 3 months of screening. Positive breath test for ethanol or positive urine or saliva screen for drugs of abuse (confirmed by repeat test) at screening or check-in that are not otherwise explained by permitted concomitant medications. Current treatment or treatment within 30 days or 5 half-lives (whichever is longer) of study drug administration with another investigational medication or current enrollment in another investigational drug study. Current treatment or treatment within 15 days or 5 half-lives (whichever is longer) before the first dose of study drug with moderate and potent inducers or inhibitors of CYP3A4 (refer to the Drug Interaction Database Program [University of Washington School of Pharmacy 2002] for prohibited drugs). Consumption of Seville oranges, grapefruit or grapefruit juice, pomelos, exotic citrus fruits, grapefruit hybrids, or fruit juices within 72 hours before the first dose of study drug. Eligible for Group 1 and have used prescription drugs within 14 days of study drug administration or nonprescription medications/products (including vitamins, minerals, and hytotherapeutic/herbal/plant-derived preparations) within 7 days of study drug administration. However, occasional use of acetaminophen and ibuprofen is permitted (see Section 6.6.1). Eligible for Groups 2 through 5 and have used prescription drugs within 14 days of study drug administration, with the exception of established therapy for renal disease and the treatment of associated disorders that have been stable for at least 7 days prior to study drug administration, as approved by the investigator and in consultation with the sponsor's medical monitor. Current or recent history (within 30 days before screening) of a clinically significant bacterial, fungal, parasitic, or mycobacterial infection, currently receiving systemic antibiotics, or having a current clinically significant viral infection at screening or check-in. History of any significant drug allergy (such as anaphylaxis or hepatotoxicity) deemed clinically relevant by the investigator. Inability to undergo venipuncture or tolerate venous access. Eligible for Group 5 and not expected to continue HD treatment for the duration of the study. Women who are pregnant or breastfeeding. Use of hormonal contraception QTcF > 450 milliseconds for Groups 1 through 3 and QTcF > 470 milliseconds for Group 4. Eligible for Group 1 and have abnormal LFT values, defined as aspartate aminotransferase, alanine aminotransferase, and serum (total and direct) bilirubin, as well as amylase and lipase above the upper limit of the normal range at screening. Eligible for Groups 2 through 4 and have values outside the normal ranges for LFTs; however, values may be acceptable if they are consistent with the participant's renal condition (if stable for 1 month prior to screening) and if the investigator (or designee) and the sponsor feel that the results are not clinically significant (based on age and renal impairment status). Receipt of live (including attenuated) vaccines within 3 months of check-in or anticipation of need for such a vaccine during the study (Note: Nonlive or inactivated vaccines are allowed up to 2 weeks prior to the first dose of study drug). Known hypersensitivity or severe reaction to INCB054707 or excipients of INCB054707 (refer to the IB).
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Incyte Corporation Call Center (US)
Phone
1.855.463.3463
Email
medinfo@incyte.com
First Name & Middle Initial & Last Name or Official Title & Degree
Incyte Corporation Call Center (ex-US)
Phone
+800 00027423
Email
eumedinfo@incyte.com
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 Name
Apex Gmbh
City
Munich
ZIP/Postal Code
D-81241
Country
Germany
Individual Site Status
Recruiting

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

Study to Evaluate the Pharmacokinetics, Safety, and Pharmacodynamics of INCB054707 in Participants With Normal and Impaired Renal Function and Participants on Hemodialysis

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