A Study to Evaluate the Effect of the Potent Cytochrome P-450 3A4 (CYP3A4) Inhibitor Itraconazole on the Pharmacokinetics (PK) of TAK-954 in Healthy Adult Participants

The drug being tested in this study is called TAK-954. TAK-954 is being tested in healthy participants in order to evaluate the effect of the potent CYP3A4 inhibitor itraconazole on the single-dose PK of TAK-954.

The study will enroll approximately 10 participants. Participants will receive the following treatment sequences:

• TAK-954 0.2 mg; Itraconazole 200 mg + TAK-954 0.2 mg

Participants will be given an intravenous infusion of TAK-954 on Day 1 of First Intervention Period (6 days) followed by minimum 7-day washout period, after which participants will be given Itraconazole capsule on Days 1 to 8 along with TAK-945 infusion on Day 4 of Second Intervention Period (9 days).

This single center trial will be conducted in the United States. The overall duration to participate in this study is 7 to 8 weeks. Participants will visit the clinic on Day -1 and remained confined until Day 6 (First Intervention Period) and Day 9 (Second Intervention Period). Participants will return for a Follow-up Visit 10 to 14 days after last dose of study drug (approximately up to Day 34).

• TAK-954 (Drug): TAK-954 Infusion
• Itraconazole (Drug): Itraconazole Capsule

Primary outcomes

• Cmax: Maximum Observed Plasma Concentration for TAK-954 [TAK-954 0.2 mg: Day 1 pre-dose and at multiple time points (up to 120 hours) post-dose; Itraconazole 200 mg and TAK-954 0.2 mg: Day 4 pre-dose and at multiple time points (up to 120 hours) post-dose]
• AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-954 [TAK-954 0.2 mg: Day 1 pre-dose and at multiple time points (up to 120 hours) post-dose; Itraconazole 200 mg and TAK-954 0.2mg: Day 1 pre-dose and at multiple time points (up to 120 hours) post-dose]

Sex: All, ages: 18 Years to 55 Years, accepts healthy volunteers

Inclusion Criteria:

1. Is a man or woman (with no child bearing potential) aged 18 to 55 years, inclusive, at the Screening Visit.
2. Has a body mass index (BMI) from greater than or equal to (>=) 18 and less than or equal to (<=) 30 kilogram per square meter (kg/m\^2) and has a body weight greater than (>) 50 kilogram (kg) at the Screening Visit.
3. Is a nonsmoker who has not used tobacco- or nicotine-containing products (example, nicotine patch) for at least 6 months before administration of the initial dose of trial drug/invasive procedure.

Exclusion Criteria:

1. Has a positive alcohol or drug screen.
2. Had major surgery, donated or lost 1 unit of blood (approximately 500 milliliter (mL)) within 8 weeks of the first dose of study drug.
3. Has a history of alcohol consumption exceeding 2 standard drinks per day on average (1 glass is approximately equivalent to: beer \[354 mL/12 ounces\], wine \[118 mL/4 ounces\], or distilled spirits \[29.5 mL/1 ounce\] per day).
4. Consumes excessive amounts, defined as greater than 6 servings (1 serving is approximately equivalent to 120 mg of caffeine) of coffee, tea, cola, energy drinks, or other caffeinated beverages per day.
5. Has a substance abuse disorder.

Participant flow

Outcome results

• Cmax: Maximum Observed Plasma Concentration for TAK-954 (Primary), Geometric mean, nanogram/milliliter (ng/mL): TAK-954 0.2 mg 2.642 +/- 0.4426; Itraconazole 200 mg and TAK-954 0.2 mg 2.840 +/- 0.6497
• AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-954 (Primary), Geometric mean, hour*nanogram per milliliter (hr*ng/mL): TAK-954 0.2 mg 28.59 +/- 6.550; Itraconazole 200 mg and TAK-954 0.2mg 43.15 +/- 10.265

Adverse events

Time frame: Treatment-emergent adverse events are adverse events that started after the first dose of study drug up to Day 9 of Second Intervention Period

Other adverse events by term

• Results publication: Chen C, Zhang L, Almansa C, Rosario M, Cwik M, Balani SK, Lock R. Evaluation of the Pharmacokinetics of Felcisetrag (TAK-954), a 5-HT4 Receptor Agonist, in the Presence and Absence of Itraconazole, a Potent CYP3A4 Inhibitor. Clin Pharmacol Drug Dev. 2022 Feb;11(2):142-149. doi: 10.1002/cpdd.1046. Epub 2022 Jan 6. PMID 34989180

• Study Protocol (PDF, 2017-05-03)
• Statistical Analysis Plan (PDF, 2017-08-08)

• Medical Director, Study director, Takeda

NIH grants: 2017