A Study to Assess the Effect of Povorcitinib on Digoxin, Rosuvastatin, and Metformin Pharmacokinetics and the Effect of Probenecid on Povorcitinib Pharmacokinetics When Administered Orally to Healthy Adult Participants

NCT06416800 | Completed Phase 1 FDA Drug

• 1 other identifier: INCB54707-110
• Study Type: interventional
• Target: 71
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to Assess the Effect of Povorcitinib on Digoxin, Rosuvastatin, and Metformin Pharmacokinetics and the Effect of Probenecid on Povorcitinib Pharmacokinetics When Administered Orally to Healthy Adult Participants.

Conditions

Healthy Participants

Keywords

INCB054707

Outcome Measures

Primary Outcomes (4)

• Pharmacokinetic (PK) in plasma digoxin

  Digoxin concentration in plasma.

  Up to Day 15

• PK in plasma rosuvastatin

  Rosuvastatin concentration in plasma.

  Up to Day 11

• PK in plasma metformin

  Metformin concentration in plasma.

  Up to Day 14

• PK in plasma povorcitinib

  Povorcitinib concentration in plasma.

  Up to Day 17

Secondary Outcomes (5)

• Number of participants with Treatment-emergent Adverse Events (TEAEs)

  Up to Day 25 (Cohorts 1, 3 and 4), Up to Day 22 (Cohort 2)

• Additional digoxin PK parameters in plasma

  Up to Day 15

• Additional rosuvastatin PK parameters in plasma

  Up to Day 11

• Additional metformin PK parameters in plasma

  Up to Day 14

• PK in plasma povorcitinib

  Up to Day 15

Study Arms (4)

Cohort 1: Dose

EXPERIMENTAL

Digoxin and povorcitinib will be administered at protocol defined doses.

Drug: Digoxin; Drug: Povorcitinib

Cohort 2: Dose

EXPERIMENTAL

Rosuvastatin and povorcitinib will be administered at protocol defined doses.

Drug: Rosuvastatin; Drug: Povorcitinib

Cohort 3: Dose

EXPERIMENTAL

Metformin and povorcitinib will be administered at protocol defined doses.

Drug: Metformin; Drug: Povorcitinib

Cohort 4: Dose

EXPERIMENTAL

Probenecid and povorcitinib will be administered at protocol defined doses.

Drug: Povorcitinib; Drug: Probenecid

Interventions

Digoxin DRUG

Oral; Tablet

Cohort 1: Dose

Rosuvastatin DRUG

Oral; Tablet

Cohort 2: Dose

Metformin DRUG

Oral; Tablet

Cohort 3: Dose

Povorcitinib DRUG

Oral; Tablet

Cohort 1: Dose; Cohort 2: Dose; Cohort 3: Dose; Cohort 4: Dose

Probenecid DRUG

Oral; Tablet

Cohort 4: Dose

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Ability to comprehend and willingness to sign a written ICF for the study.
• Aged 18 to 55 years, inclusive, at the time of signing the ICF.
• BMI between 18.0 and 30.5 kg/m2, inclusive. Participants with a BMI up to 32.0 kg/m2 may be enrolled with the sponsor's approval.
• No clinically significant findings on screening evaluations (eg, clinical, laboratory, and ECG evaluations).
• Ability to swallow and retain oral medication.
• Willingness to avoid pregnancy or fathering children based on the criteria below:
• Male participants with reproductive potential must agree to take appropriate precautions to avoid fathering children from screening through 90 days (a spermatogenesis cycle) after the last dose of study treatment and must refrain from donating sperm during this period. Permitted methods in preventing pregnancy should be communicated to the participants and their understanding confirmed.
• Female participants must have a negative serum pregnancy test at screening and a negative urine pregnancy test at check-in on Day -1 and must agree to take appropriate precautions to avoid pregnancy from screening through 30 days (1 menstrual cycle) after the last dose of study treatment and must refrain from donating oocytes during this period. Permitted methods in preventing pregnancy should be communicated to the participants and their understanding confirmed.
• Female participants not considered to be of childbearing potential are eligible.

You may not qualify if:

• History of uncontrolled or unstable cardiovascular, respiratory, renal, gastrointestinal, endocrine, hematopoietic, psychiatric, and/or neurological disease within 6 months of screening.
• History of cardiovascular, cerebrovascular, peripheral vascular, or thrombotic disease or uncontrolled hypertension (ie, systolic blood pressure \> 140 mmHg or diastolic blood pressure \> 90 mmHg at screening, confirmed by repeat testing).
• History or presence of cardiovascular symptoms including but not limited to chest pain or pressure, palpitations, irregular heartbeat, syncope (excluding vasovagal from phlebotomy), dyspnea at rest or on exertion, lightheadedness, orthopnea, or paroxysmal nocturnal dyspnea that is considered clinically significant by the investigator.
• Resting pulse \< 40 bpm or \> 100 bpm at screening, confirmed by repeat testing.
• History or presence of an abnormal ECG before initial dose administration that, in the investigator's opinion, is clinically significant (ie, a QTcF interval \> 450 milliseconds for males and \> 470 milliseconds for females, QRS interval \> 120 milliseconds, and PR interval \> 220 milliseconds).
• Presence or history of a malabsorption syndrome (eg, Crohn's disease or chronic pancreatitis) that could affect drug absorption.
• Vitamin B12, folate, TSH, or parathyroid hormone levels less than the laboratory LLN at screening that are also clinically significant in the opinion of the investigator.
• ALT, AST, ALP, or total bilirubin \> 1.25 × the laboratory-defined ULN at screening or check-in, confirmed by repeat testing (except participants with Gilbert's disease, for whom total bilirubin must be ≤ 2.0 × ULN).
• History of malignancy within 5 years before screening, with the exception of cured basal cell or squamous cell carcinoma of the skin, ductal carcinoma in situ, or Gleason 6 prostate cancer.
• Current or recent (within 3 months before screening) clinically significant gastrointestinal disease or surgery (including cholecystectomy; excluding appendectomy) that could affect drug absorption.
• Any major surgery within 4 weeks of screening.
• Donation of blood to a blood bank or participation in a clinical study (except a screening visit) within 4 weeks before screening (within 2 weeks for plasma-only donation).
• Blood transfusion within 4 months before check-in (Day -1).
• Chronic or current active infectious disease requiring systemic antibiotic, antifungal, or antiviral treatment (includes latent treated tuberculosis).
• Positive test 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.

Sponsors & Collaborators

• Incyte Corporation: lead

Study Sites (1)

Fortrea Clinical Research Unit

Dallas, Texas, 75247, United States

Location

Related Links

• A Study to Assess the Effect of Povorcitinib on Digoxin, Rosuvastatin, and Metformin Pharmacokinetics and the Effect of Probenecid on Povorcitinib Pharmacokinetics When Administered Orally to Healthy Adult Participants

MeSH Terms

Interventions

Digoxin; Rosuvastatin Calcium; Metformin; Probenecid

Intervention Hierarchy (Ancestors)

Digitalis Glycosides; Cardenolides; Cardiac Glycosides; Cardanolides; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Glycosides; Carbohydrates; Sulfonamides; Amides; Organic Chemicals; Fluorobenzenes; Hydrocarbons, Fluorinated; Hydrocarbons, Halogenated; Hydrocarbons; Sulfones; Sulfur Compounds; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Biguanides; Guanidines; Amidines

Study Officials

• Incyte Medical Monitor

  Incyte Corporation

  STUDY DIRECTOR

Study Design

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

Study Record Dates

• First Submitted: April 29, 2024
• First Posted: May 16, 2024
• Study Start: June 19, 2024
• Primary Completion: January 15, 2025
• Study Completion: January 15, 2025
• Last Updated: February 6, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)