A Study of Interaction of Zasocitinib (TAK-279) With Other Medicines in Healthy Adults

A Phase 1, Open-Label, 4-Part Trial to Assess the Drug-Drug Interaction Between Zasocitinib and Combined Oral Contraceptives, a MATE Substrate, a P-gp Substrate, and a Proton-Pump Inhibitor in Healthy Participants

The main aim of this study is to find out how zasocitinib (TAK-279) interacts with other medicines taken by mouth (orally). This will be examined by how the body processes medicines, which is called pharmacokinetics or PK. In this study, other medicines that will be administered together with zasocitinib include a contraceptive (levonorgestrel (LNG) and ethinyl estradiol [EE]), a medicine for diabetes (metformin), a medicine used for heart problems (digoxin), and a medicine that blocks the production of stomach acid (esomeprazole).

Another aim is to learn about the side effects of zasocitinib and how well it is tolerated when taken alone and together with these other medicines.

During the study, participants will need to stay at the clinic for up to 27 days.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers
• Intervention / Treatment: Drug: Zasocitinib; Drug: COC; Drug: Metformin; Drug: Digoxin; Drug: Esomeprazole

Detailed Description

The drug being tested in this study is called zasocitinib.

Zasocitinib is being tested to assess the effect of zasocitinib on the pharmacokinetics of Combined Oral Contraceptive (COC [containing LNG and EE] in Part 1), multidrug and toxic compound extrusion (MATE) substrate (metformin in Part 2), and a P-glycoprotein (P-gp) substrate (digoxin in Part 3). Additionally, the effect of proton-pump inhibitor (PPI) (esomeprazole in Part 4) on the pharmacokinetics of zasocitinib is being evaluated in healthy participants.

The study will enroll approximately 78 participants. Participants will be enrolled in one of the four parts to evaluate the following treatments:

• Part 1: COC (LNG and EE) + Zasocitinib
• Part 2: Metformin + Zasocitinib
• Part 3: Digoxin + Zasocitinib
• Part 4: Zasocitinib + Esomeprazole

The overall time (including screening and follow-up periods) to participate is approximately 68 days for Part 1, 54 days for Part 2, 62 days for Part 3 and 56 days for Part 4. All participants will be followed up for up to 14 days after the last dose of Period 2 in each Part.

• Study Type: Interventional
• Enrollment (Actual): 78
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Tempe, Arizona, United States, 85283
      • Celerion

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion criteria:

1. Body mass index (BMI) greater than or equal to (>=) 18.0 and less than or equal to (<=) 32.0 kilograms per square meter (kg/m^2) at the screening visit.

2. Medically healthy with no clinically significant medical history, physical examination, laboratory profiles, vital signs, and Electrocardiograms (ECGs) as outlined in the protocol.

   Part 1 Only:

3. Healthy, adult, female, aged 18 to 65 years, inclusive, at the screening visit.

   Parts 2-4 Only:

4. Healthy, adult, male or female, aged 18 to 55 years, inclusive, at the screening visit.

Exclusion criteria:

1. Positive urine drug or alcohol results at the screening visit or at check-in.

2. Unable to refrain from or anticipates the use of:

   • Any drugs, including prescription and non-prescription medications, herbal remedies, or vitamin supplements and other drugs outlined in protocol.
   • Any drugs known to be inducers of Cytochrome P450 3A4 (CYP3A4) and/or P-gp, including St. John's Wort, for 28 days prior to the first dosing.
3. Has been on a diet incompatible with the on-trial diet, in the opinion of the investigator or designee, within the 30 days prior to first dosing and throughout the trial.
4. Has made a donation of blood or had significant blood loss within 56 days prior to first dosing.
5. Has made a plasma donation within 7 days prior to first dosing.
6. Participated in another clinical trial within 30 days prior to first dosing. The 30-day window will be derived from the date of the last dosing in the previous trial to Day 1 of Period 1 of the current trial.
7. Has herpes infections.
8. Positive results for non-herpetic viral diseases at the screening visit.

9. Positive results for tuberculosis (TB) at the screening visit.

   Part 1:

10. Unable to refrain from or anticipates the use of:

    • Any drugs known to increase or decrease levels of sex hormone-binding globulin (SHBG), including any oral, topical, or intravaginal hormone-containing product, within 12 weeks prior to the first dosing.
    • Any injectable or implantable hormone-containing product within 1 year prior to the first dosing.

    Part 2 Only:

11. Hemoglobin A1c (HbA1c) greater than (>) ULN (5.7 percentage [%]) and deemed clinically significant by the investigator or designee at the screening visit.

    Part 3 Only:

12. Has or is at risk for major cardiac events or dysfunction.

    Part 4 Only:

13. Had diarrhea or vomiting within 48 hours prior to check-in.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1: COC (LNG and EE) + Zasocitinib	Drug: Zasocitinib; Zasocitinib tablets specified doses on specified days.; Other Names: TAK- 279; Drug: COC; COC tablets (containing LNG and EE) specified doses on specified days.
Experimental: Part 2: Metformin + Zasocitinib	Drug: Zasocitinib; Zasocitinib tablets specified doses on specified days.; Other Names: TAK- 279; Drug: Metformin; Metformin tablets specified doses on specified days.
Experimental: Part 3: Digoxin + Zasocitinib	Drug: Zasocitinib; Zasocitinib tablets specified doses on specified days.; Other Names: TAK- 279; Drug: Digoxin; Digoxin tablets specified doses on specified days.
Experimental: Part 4: Zasocitinib + Esomeprazole	Drug: Zasocitinib; Zasocitinib tablets specified doses on specified days.; Other Names: TAK- 279; Drug: Esomeprazole; Esomeprazole capsules specified doses on specified days.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Part 1: Cmax: Maximum Observed Plasma Concentration for LNG and EE When Administered Alone and With Zasocitinib	Up to 144 hours
Part 1: AUCinf: Area Under the Plasma Concentration-time Curve from Time 0 to Infinity for LNG and EE When Administered Alone and With Zasocitinib	Up to 144 hours
Part 1: AUClast: Area Under the Plasma Concentration-Time Curve from Time 0 to the Time of the Last Quantifiable Concentration for LNG and EE When Administered Alone and With Zasocitinib	Up to 144 hours
Part 2: Cmax for Metformin When Administered Alone and With Zasocitinib	Up to 48 hours
Part 2: AUCinf for Metformin When Administered Alone and With Zasocitinib	Up to 48 hours
Part 2: AUClast for Metformin When Administered Alone and With Zasocitinib	Up to 48 hours
Part 3: Cmax for Digoxin When Administered Alone and With Zasocitinib	Up to 144 hours
Part 3: AUCinf for Digoxin When Administered Alone and With Zasocitinib	Up to 144 hours
Part 3: AUClast for Digoxin When Administered Alone and With Zasocitinib	Up to 144 hours
Part 4: Cmax for Zasocitinib When Administered Alone and With Esomeprazole	Up to 120 hours
Part 4: AUCinf for Zasocitinib When Administered Alone and With Esomeprazole	Up to 120 hours
Part 4: AUClast for Zasocitinib When Administered Alone and With Esomeprazole	Up to 120 hours

Secondary Outcome Measures

Outcome Measure	Time Frame
Parts 1, 2, 3 and 4: Number of Participants with Treatment-emergent Adverse Events (TEAEs) and Adverse Events of Special Interest (AESIs)	Part 1: Up to 33 days; Part 2: Up to 23 days; Part 3: Up to 27 days; Part 4: Up to 23 days

Collaborators and Investigators

• Sponsor: Takeda
• Investigators: Study Director: Study Director, Takeda

Publications and helpful links

Helpful Links

• Click here for more information about this trial in easy-to-understand language, including a Plain Language Summary of the results if the trial has been completed.

Study record dates

Study Major Dates

• Study Start (Actual): January 23, 2025
• Primary Completion (Actual): March 11, 2025
• Study Completion (Actual): March 30, 2025

Study Registration Dates

• First Submitted: January 21, 2025
• First Submitted That Met QC Criteria: January 21, 2025
• First Posted (Actual): January 27, 2025

Study Record Updates

• Last Update Posted (Actual): April 4, 2025
• Last Update Submitted That Met QC Criteria: April 3, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Keywords: Drug Therapy
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Hypoglycemic Agents; Gastrointestinal Agents; Enzyme Inhibitors; Anti-Arrhythmia Agents; Protective Agents; Cardiotonic Agents; Anti-Ulcer Agents; Proton Pump Inhibitors; Digoxin; Metformin; Esomeprazole
• Other Study ID Numbers: TAK-279-1011

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.
• IPD Sharing Access Criteria: IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No