A Study of the Interaction of TAK-279 With Substances That Have an Impact on Metabolism in Healthy Adults

Sponsor

Takeda (Industry)

Overall Status

Not yet recruiting

CT.gov ID

NCT05995249

Collaborator

(none)

Enrollment

Location

Arms

Anticipated Duration (Months)

16.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The main aim of this study is to find out how the body of a healthy adult processes TAK-279 (pharmacokinetics) when substances that either hinder or help the human metabolism such as erythromycin, phenytoin and efavirenz are given along with TAK-279. Other aim is to learn about side effects and how well it is tolerated when TAK-279 is given alone and together with substances that impact human metabolism.

The participants will need to stay at the clinic for up to 26 days.

Condition or Disease	Intervention/Treatment	Phase
Healthy Volunteers	Drug: TAK-279 Drug: Erythromycin Drug: Phenytoin Drug: Efavirenz	Phase 1

Detailed Description

The drug being tested in this study is called TAK-279. TAK-279 is being tested to assess the effect of a moderate CYP3A4 inhibitor (erythromycin- Part 1), and of strong (phenytoin- Part 2) and moderate (efavirenz- Part 3) CYP3A4 inducers on the pharmacokinetics of TAK-279 in healthy participants.

The study will enroll approximately 48 patients. Participants will be enrolled in one of the three parts to receive a single dose of TAK-279 in both Period 1 and Period 2 along with multiple doses of either erythromycin, phenytoin or efavirenz in Period 2 as given below:

Part 1, Treatment A + Treatment B: TAK-279 50 mg + Erythromycin 500 mg
Part 2, Treatment C + Treatment D: TAK-279 50 mg + Phenytoin 100 mg
Part 3, Treatment E + Treatment F: TAK-279 50 mg + Efavirenz 600 mg

All participants will be monitored for up to 14 days postdose in each Part. Based on an evaluation of the results from Parts 1 and 2, participants will be enrolled for Part 3.

This single-center trial will be conducted in the United States. The overall study duration is approximately 58 days for Part 1, 66 days for Part 2, and 63 days for Part 3.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

48 participants

Allocation:

Non-Randomized

Intervention Model:

Sequential Assignment

Masking:

None (Open Label)

Primary Purpose:

Prevention

Official Title:

A Phase 1, 3-Part, Open-label, Drug-Drug Interaction Study to Evaluate the Effect of a Moderate CYP3A4 Inhibitor, and of Strong and Moderate CYP3A4 Inducers on the Pharmacokinetics of TAK-279 in Healthy Subjects

Anticipated Study Start Date :

Aug 11, 2023

Anticipated Primary Completion Date :

Nov 9, 2023

Anticipated Study Completion Date :

Nov 9, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Part 1, Treatment A + Treatment B: TAK-279 50 mg + Erythromycin 500 mg Participants will receive single oral dose of TAK-279 50 mg, on Day 1 of Period 1. Following Period 1 participants will receive single oral dose of TAK-279 50 mg, on Day 5 and erythromycin 500 mg orally thrice daily (TID) on Day 1 through Day 10 of Period 2 in Part 1 of the study.	Drug: TAK-279 TAK-279 capsules Drug: Erythromycin Erythromycin tablets
Experimental: Part 2, Treatment C + Treatment D: TAK-279 50 mg + Phenytoin 100 mg Participants will receive single oral dose of TAK-279 50 mg, on Day 1 of Period 1. Following Period 1 participants will receive single oral dose of TAK-279 50 mg on Day 14 and phenytoin 100 mg orally TID on Day 1 through Day 18 of Period 2 in Part 2 of the study.	Drug: TAK-279 TAK-279 capsules Drug: Phenytoin Phenytoin capsules
Experimental: Part 3, Treatment E + Treatment F: TAK-279 50 mg + Efavirenz 600 mg Participants will receive single oral dose of TAK-279 50 mg, on Day 1 of Period 1. Following Period 1 participants will receive single oral dose of TAK-279 50 mg on Day 11 and efavirenz 600 mg orally once daily (QD) on Day 1 through Day 15 of Period 2 in Part 3 of the study.	Drug: TAK-279 TAK-279 capsules Drug: Efavirenz Efavirenz tablets

Arm

Intervention/Treatment

Experimental: Part 1, Treatment A + Treatment B: TAK-279 50 mg + Erythromycin 500 mg

Participants will receive single oral dose of TAK-279 50 mg, on Day 1 of Period 1. Following Period 1 participants will receive single oral dose of TAK-279 50 mg, on Day 5 and erythromycin 500 mg orally thrice daily (TID) on Day 1 through Day 10 of Period 2 in Part 1 of the study.

Drug: TAK-279

TAK-279 capsules

Drug: Erythromycin

Erythromycin tablets

Experimental: Part 2, Treatment C + Treatment D: TAK-279 50 mg + Phenytoin 100 mg

Participants will receive single oral dose of TAK-279 50 mg, on Day 1 of Period 1. Following Period 1 participants will receive single oral dose of TAK-279 50 mg on Day 14 and phenytoin 100 mg orally TID on Day 1 through Day 18 of Period 2 in Part 2 of the study.

Drug: TAK-279

TAK-279 capsules

Drug: Phenytoin

Phenytoin capsules

Experimental: Part 3, Treatment E + Treatment F: TAK-279 50 mg + Efavirenz 600 mg

Participants will receive single oral dose of TAK-279 50 mg, on Day 1 of Period 1. Following Period 1 participants will receive single oral dose of TAK-279 50 mg on Day 11 and efavirenz 600 mg orally once daily (QD) on Day 1 through Day 15 of Period 2 in Part 3 of the study.

Drug: TAK-279

TAK-279 capsules

Drug: Efavirenz

Efavirenz tablets

Outcome Measures

Primary Outcome Measures

Parts 1, 2, and 3: Cmax: Maximum Observed Plasma Concentration for TAK-279 [Predose and at multiple timepoints post dose from Day 1 up to Day 11 in Part 1, up to Day 19 in Part 2 and up to Day 16 in Part 3]
Parts 1, 2, and 3: AUC∞: Area Under the Plasma Concentration-time Curve from Time 0 to Infinity for TAK-279 [Predose and at multiple timepoints post dose from Day 1 up to Day 11 in Part 1, up to Day 19 in Part 2 and up to Day 16 in Part 3]
Parts 1, 2, and 3: AUClast: Area Under the Plasma Concentration-Time Curve from Time 0 to the Time of the Last Quantifiable Concentration for TAK-279 [Predose and at multiple timepoints post dose from Day 1 up to Day 11 in Part 1, up to Day 19 in Part 2 and up to Day 16 in Part 3]

Secondary Outcome Measures

Parts 1, 2, and 3: Number of Participants with Treatment-emergent Adverse Events (TEAEs) [From Day 1 of period 1 through Day 14 after the last dose in period 2 (up to approximately 66 days)]
Part 2 and Part 3: Number of Participants with Suicidal Ideation as per the Columbia-suicide Severity Rating Scale (C-SSRS) [Predose and at multiple timepoints post dose from Day 1 up to Day 11 in Part 1, up to Day 19 in Part 2 and up to Day 16 in Part 3]
The C-SSRS systematically tracks suicidal ideation and behavior. The total score range is 0 (no ideation is present) to 5 (active suicidal ideation with specific plan and intent). The higher the score, the greater one's suicidal ideation.
Parts 1, 2, and 3: Number of Participants with Abnormal Vital Signs [From Day 1 of period 1 through Day 14 after the last dose in period 2 (up to approximately 66 days)]
Abnormal vital sign assessment will include assessments of systolic and diastolic blood pressure, pulse rate, respiration rate, body temperature as determined by the investigator.
Parts 1, 2, and 3: Number of Participants with Abnormal Electrocardiogram Findings [From Day 1 of period 1 through Day 14 after the last dose in period 2 (up to approximately 66 days)]
Abnormal 12-lead ECG findings will include heart rate and measures PR, QRS, QT and QTcF intervals. 12-lead ECG recordings were obtained after the participants have rested for at least 5 minutes in supine position as determined by the investigator.
Parts 1, 2, and 3: Number of Participants with Abnormal Laboratory Values [From Day 1 of period 1 through Day 14 after the last dose in period 2 (up to approximately 66 days)]
Abnormal laboratory investigation will include hematology, chemistry, and urinalysis analysis as determined by the investigator.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 55 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion criteria:

Understands the study procedures in the informed consent form (ICF), and be willing and able to comply with the protocol.
Healthy, adult, male or female of non-childbearing potential, 18-55 years of age, inclusive, at the screening visit.
Male participants must follow protocol specified contraception guidance.
Continuous non-smoker who has not used nicotine- and tobacco-containing products for at least 3 months prior to the first dosing based on participant self-reporting.
Body mass index (BMI) ≥ 18.0 and ≤ 32.0 kg/m^2 at the screening visit.
Medically healthy with no clinically significant medical history, physical examination, laboratory profiles, vital signs, and electrocardiograms (ECGs), as deemed by the Investigator or designee, including the following:

Seated blood pressure (BP) is ≥ 90/40 millimeter of mercury (mmHg) and ≤ 140/90 mmHg at the screening visit.
Seated pulse rate is ≥ 40 beats per minute (bpm) and ≤ 99 bpm at the screening visit.
Part 1 only: QTcF interval is ≤ 450 msec (males and females) and has ECG findings considered normal or not clinically significant by the Investigator or designee at the screening visit.
Part 2 and 3: ECG findings considered normal or not clinically significant by the Investigator or designee at the screening visit.
Estimated glomerular filtration rate (eGFR) ≥ 80 mL/min/1.73m2 at the screening visit.
Liver function tests including Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Alkaline phosphatase (ALP), and total bilirubin ≤ upper limit of normal (ULN) at the screening visit and at check-in.
No clinically significant hypokalemia or hypomagnesemia at the screening visit.

Exclusion criteria:

Is mentally or legally incapacitated or has significant emotional problems at the time of the screening visit or expected during the conduct of the study.
History or presence of clinically significant medical or psychiatric condition or disease in the opinion of the Investigator or designee.
History of any illness that, in the opinion of the Investigator or designee, might confound the results of the study or poses an additional risk to the participant by their participation in the study.
Has a history of any of the following:

Active infection or febrile illness within 7 days prior to first dosing, as assessed by the Investigator or designee.
Symptoms suggestive of systemic or invasive infection requiring hospitalization or treatment within 8 weeks prior to first dosing.
Chronic or recurrent bacterial disease, including but not limited to chronic pyelonephritis or cystitis, chronic bronchitis/pneumonitis, osteomyelitis, or chronic skin ulcerations/infections or fungal infections (except superficial nailbed mycosis).
An infected joint prosthesis unless that prosthesis has been removed or replaced greater than 60 days prior to first dosing.
Opportunistic infections.
Cancer or lymphoproliferative disease within 5 years prior to first dosing.
Known or suspected condition/illness that is consistent with compromised immunity, including but not limited to any identified congenital or acquired immunodeficiency; splenectomy.
Liver or other solid organ transplant.

Has history or presence of alcoholism and/or drug abuse within the past 2 years prior to first dosing, as determined by the Investigator or designee.
History or presence of hypersensitivity or idiosyncratic reaction to the study drugs, including macrolide antibiotics (Part 1 only; eg, erythromycin) or anti-seizure agents (Part 2 only; eg, phenytoin) or anti-viral drugs (Part 3 only; eg, efavirenz).
Part 2 and Part 3 only: Any positive responses on the Columbia-Suicide Severity Rating Scale (C-SSRS) or has a risk of suicide according to the Investigator's or designee judgment based on the assessment of the C-SSRS at the screening visit or check-in or has made a suicide attempt within 12 months before the first dosing.
Part 2 only: History of seizure, epilepsy, severe head injury, multiple sclerosis, or other known neurological conditions which the Investigator or designee considers to be clinically significant.