## Protocol Section
### Identification Module
**NCT ID:** NCT06416800

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

**Official Title:** An Open-Label Study to Assess the Effect of Povorcitinib on Digoxin, Rosuvastatin, and Metformin Pharmacokinetics When Administered Orally to Healthy Adult Participants

#### Organization Study ID Info
**ID:** INCB54707-110
#### Organization
**Class:** INDUSTRY
**Full Name:** Incyte Corporation
### Status Module
#### Completion Date
**Date:** 2024-08-10

**Type:** ESTIMATED

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2024-05-23

**Type:** ACTUAL

**Last Update Submit Date:** 2024-05-22

**Overall Status:** RECRUITING

#### Primary Completion Date
**Date:** 2024-08-10

**Type:** ESTIMATED

#### Start Date
**Date:** 2024-06-19

**Type:** ESTIMATED

**Status Verified Date:** 2024-05

#### Study First Post Date
**Date:** 2024-05-16
**Type:** ACTUAL
**Study First Submit Date:** 2024-04-29
**Study First Submit QC Date:** 2024-05-15
### Sponsor Collaborators Module

#### Lead Sponsor

**Class:** INDUSTRY

**Name:** Incyte Corporation

#### Responsible Party

**Type:** SPONSOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** True

### Description Module

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

### Conditions Module

**Conditions:**

- Healthy Participants

**Keywords:**

- INCB054707

### Design Module

#### Design Info

**Allocation:** RANDOMIZED

**Intervention Model:** PARALLEL

##### Masking Info

**Masking:** NONE

**Primary Purpose:** TREATMENT

#### Enrollment Info

**Count:** 54

**Type:** ESTIMATED

**Phases:**

- PHASE1

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** Digoxin and povorcitinib will be administered at protocol defined doses.

**Intervention Names:**

- Drug: Digoxin

- Drug: Povorcitinib

**Label:** Cohort 1: Dose

**Type:** EXPERIMENTAL

#### Arm Group 2

**Description:** Rosuvastatin and povorcitinib will be administered at protocol defined doses.

**Intervention Names:**

- Drug: Rosuvastatin

- Drug: Povorcitinib

**Label:** Cohort 2: Dose

**Type:** EXPERIMENTAL

#### Arm Group 3

**Description:** Metformin and povorcitinib will be administered at protocol defined doses.

**Intervention Names:**

- Drug: Metformin

- Drug: Povorcitinib

**Label:** Cohort 3: Dose

**Type:** EXPERIMENTAL

### Interventions

#### Intervention 1

**Arm Group Labels:**

- Cohort 1: Dose

**Description:** Oral; Tablet

**Name:** Digoxin

**Type:** DRUG

#### Intervention 2

**Arm Group Labels:**

- Cohort 2: Dose

**Description:** Oral; Tablet

**Name:** Rosuvastatin

**Type:** DRUG

#### Intervention 3

**Arm Group Labels:**

- Cohort 3: Dose

**Description:** Oral; Tablet

**Name:** Metformin

**Type:** DRUG

#### Intervention 4

**Arm Group Labels:**

- Cohort 1: Dose

- Cohort 2: Dose

- Cohort 3: Dose

**Description:** Oral; Tablet

**Name:** Povorcitinib

**Type:** DRUG

### Outcomes Module

#### Primary Outcomes

**Description:** Digoxin concentration in plasma.

**Measure:** Pharmacokinetic (PK) in plasma digoxin

**Time Frame:** Up to Day 15

**Description:** Rosuvastatin concentration in plasma.

**Measure:** PK in plasma rosuvastatin

**Time Frame:** Up to Day 11

**Description:** Metformin concentration in plasma.

**Measure:** PK in plasma metformin

**Time Frame:** Up to Day 14

#### Secondary Outcomes

**Description:** Defined as any adverse event, either reported for the first time or the worsening of a pre-existing event, occurring after first dose of study treatment.

**Measure:** Number of participants with Treatment-emergent Adverse Events (TEAEs)

**Time Frame:** Up to Day 25 (Cohorts 1 and 3), Up to Day 22 (Cohort 2)

**Description:** Additional digoxin concentration in plasma.

**Measure:** Additional digoxin PK parameters in plasma

**Time Frame:** Up to Day 15

**Description:** Additional rosuvastatin concentration in plasma.

**Measure:** Additional rosuvastatin PK parameters in plasma

**Time Frame:** Up to Day 11

**Description:** Additional metformin concentration in plasma.

**Measure:** Additional metformin PK parameters in plasma

**Time Frame:** Up to Day 14

**Description:** Povorcitinib concentration in plasma.

**Measure:** PK in plasma povorcitinib

**Time Frame:** Up to Day 15

### Eligibility Module

**Eligibility Criteria:** Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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.
* Hemoglobin, WBC count, platelet count, or absolute neutrophil count less than the laboratory LLN at screening or check-in, confirmed by repeat testing. Hemoglobin, WBC, platelet, and neutrophil abnormalities must also be clinically significant in the opinion of the investigator to be exclusionary.
* 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.
* Receipt of live (including attenuated) vaccines within 28 days before the first dose of study treatment or anticipation of need for such a vaccine during the study. Note: Nonlive or inactivated vaccines are allowed up to 2 weeks before the first dose of study treatment.
* History of significant alcohol use within 3 months before screening.
* Positive urine or breath test for ethanol or positive urine or serum screen for drugs of abuse that are not otherwise explained by permitted concomitant medications or diet.
* Current treatment, or treatment within 30 days or 5 half-lives (whichever is longer) before the first dose of study treatment, with another investigational medication or current enrollment in another investigational drug study.
* Current treatment, or treatment within 30 days or 5 half-lives (whichever is longer) before the first dose of study treatment, with an inducer or inhibitor of CYP3A4, P-gp, or BCRP (refer to the Drug Interaction Database \[2024\] 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 treatment.
* Current use of prohibited medication.
* History of any significant drug allergy (such as anaphylaxis or hepatotoxicity) deemed clinically relevant by the investigator.
* Known hypersensitivity or severe reaction to povorcitinib or any excipients of povorcitinib, digoxin, rosuvastatin, or metformin (refer to the IB and applicable package inserts).
* Inability to undergo venipuncture or tolerate venous access.
* History of tobacco- or nicotine-containing product-use within 1 month before screening. However, use of nicotine-containing products prior to screening that is equivalent to ≤ 2 cigarettes per week may be permitted at the discretion of the investigator.
* Use of prescription drugs (including hormonal contraceptives) within 14 days before study treatment administration or nonprescription medications/products (including vitamins, minerals, and phytotherapeutic/herbal/plant-derived preparations) within 7 days of study treatment administration. However, occasional paracetamol, ibuprofen, and standard-dose multivitamins are permitted.
* Women who are pregnant or breastfeeding.
* Any condition that would, in the investigator's judgment, interfere with full participation in the study, including administration of study treatment and attending required study visits; pose a significant risk to the participant; or interfere with interpretation of study data.
* An eGFR \< 90 mL/min/1.73 m2, based on the site's standard formula, at screening. A repeat measurement may be allowed at the investigator's discretion.

**Healthy Volunteers:** True

**Maximum Age:** 55 Years

**Minimum Age:** 18 Years

**Sex:** ALL

**Standard Ages:**

- ADULT

### Contacts Locations Module

#### Central Contacts

**Contact 1:**

**Email:** medinfo@incyte.com

**Name:** Incyte Corporation Call Center (US)

**Phone:** 1.855.463.3463

**Role:** CONTACT

**Contact 2:**

**Email:** eumedinfo@incyte.com

**Name:** Incyte Corporation Call Center (ex-US)

**Phone:** +800 00027423

**Role:** CONTACT

#### Locations

**Location 1:**

**City:** Dallas

**Country:** United States

**Facility:** Fortrea Clinical Research Unit

**State:** Texas

**Status:** RECRUITING

**Zip:** 75247

#### Overall Officials

**Official 1:**

**Affiliation:** Incyte Corporation

**Name:** Incyte Medical Monitor

**Role:** STUDY_DIRECTOR

### IPD Sharing Statement Module

**IPD Sharing:** NO

## Derived Section

### Intervention Browse Module - Ancestors

- ID: D000007004

- Term: Hypoglycemic Agents

- ID: D000045505

- Term: Physiological Effects of Drugs

- ID: D000000924

- Term: Anticholesteremic Agents

- ID: D000000960

- Term: Hypolipidemic Agents

- ID: D000000963

- Term: Antimetabolites

- ID: D000045504

- Term: Molecular Mechanisms of Pharmacological Action

- ID: D000057847

- Term: Lipid Regulating Agents

- ID: D000019161

- Term: Hydroxymethylglutaryl-CoA Reductase Inhibitors

- ID: D000004791

- Term: Enzyme Inhibitors

- ID: D000000889

- Term: Anti-Arrhythmia Agents

- ID: D000002316

- Term: Cardiotonic Agents

- ID: D000020011

- Term: Protective Agents

### Intervention Browse Module - Browse Branches

- Abbrev: Hypo

- Name: Hypoglycemic Agents

- Abbrev: All

- Name: All Drugs and Chemicals

- Abbrev: AnArAg

- Name: Anti-Arrhythmia Agents

- Abbrev: CaAg

- Name: Cardiotonic Agents

- Abbrev: Lipd

- Name: Lipid Regulating Agents

- Abbrev: BDCA

- Name: Bone Density Conservation Agents

### Intervention Browse Module - Browse Leaves

- ID: M11667

- Name: Metformin

- Relevance: HIGH

- As Found: Assessment

- ID: M7265

- Name: Digoxin

- Relevance: HIGH

- As Found: Fascia

- ID: M298

- Name: Rosuvastatin Calcium

- Relevance: HIGH

- As Found: Available

- ID: M5381

- Name: Calcium

- Relevance: LOW

- As Found: Unknown

- ID: M5398

- Name: Calcium, Dietary

- Relevance: LOW

- As Found: Unknown

- ID: M10054

- Name: Hypoglycemic Agents

- Relevance: LOW

- As Found: Unknown

- ID: M4243

- Name: Anticholesteremic Agents

- Relevance: LOW

- As Found: Unknown

- ID: M4278

- Name: Hypolipidemic Agents

- Relevance: LOW

- As Found: Unknown

- ID: M4281

- Name: Antimetabolites

- Relevance: LOW

- As Found: Unknown

- ID: M28883

- Name: Lipid Regulating Agents

- Relevance: LOW

- As Found: Unknown

- ID: M21155

- Name: Hydroxymethylglutaryl-CoA Reductase Inhibitors

- Relevance: LOW

- As Found: Unknown

- ID: M7951

- Name: Enzyme Inhibitors

- Relevance: LOW

- As Found: Unknown

- ID: M4213

- Name: Anti-Arrhythmia Agents

- Relevance: LOW

- As Found: Unknown

- ID: M5572

- Name: Cardiotonic Agents

- Relevance: LOW

- As Found: Unknown

- ID: M21869

- Name: Protective Agents

- Relevance: LOW

- As Found: Unknown

### Intervention Browse Module - Meshes

- ID: D000008687

- Term: Metformin

- ID: D000004077

- Term: Digoxin

- ID: D000068718

- Term: Rosuvastatin Calcium

### Misc Info Module

- Version Holder: 2024-05-31
