Clinical trial NCT06793943: A Study of Interaction of Zasocitinib (TAK-279) With Other Medicines in Healthy Adults
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteers
Keywords: Drug Therapy
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2025-01-27
Enrollment: 78
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Part 1: Cmax: Maximum Observed Plasma Concentration for LNG and EE When Administered Alone and With Zasocitinib
timeFrame: Up to 144 hours
measure: 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
timeFrame: Up to 144 hours
measure: 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
timeFrame: Up to 144 hours
measure: Part 2: Cmax for Metformin When Administered Alone and With Zasocitinib
timeFrame: Up to 48 hours
measure: Part 2: AUCinf for Metformin When Administered Alone and With Zasocitinib
timeFrame: Up to 48 hours
measure: Part 2: AUClast for Metformin When Administered Alone and With Zasocitinib
timeFrame: Up to 48 hours
measure: Part 3: Cmax for Digoxin When Administered Alone and With Zasocitinib
timeFrame: Up to 144 hours
measure: Part 3: AUCinf for Digoxin When Administered Alone and With Zasocitinib
timeFrame: Up to 144 hours
measure: Part 3: AUClast for Digoxin When Administered Alone and With Zasocitinib
timeFrame: Up to 144 hours
measure: Part 4: Cmax for Zasocitinib When Administered Alone and With Esomeprazole
timeFrame: Up to 120 hours
measure: Part 4: AUCinf for Zasocitinib When Administered Alone and With Esomeprazole
timeFrame: Up to 120 hours
measure: Part 4: AUClast for Zasocitinib When Administered Alone and With Esomeprazole
timeFrame: Up to 120 hours
Secondary outcomes:
measure: Parts 1, 2, 3 and 4: Number of Participants with Treatment-emergent Adverse Events (TEAEs) and Adverse Events of Special Interest (AESIs)
timeFrame: Part 1: Up to 33 days; Part 2: Up to 23 days; Part 3: Up to 27 days; Part 4: Up to 23 days
Other outcomes:
Locations:
city: Tempe
country: United States
facility: Celerion
state: Arizona
Study officials:
affiliation: Takeda
name: Study Director
role: STUDY_DIRECTOR
References: