Clinical trial NCT03173170: 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
Official title: A Single-Sequence, Open-Label, 2-Period Crossover Trial to Evaluate the Effect of the Potent Cytochrome P-450 3A4 Inhibitor Itraconazole on the Pharmacokinetics of TAK-954 in Healthy Adult Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Participants
Keywords: Drug Therapy
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2017-06-01
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: OTHER

Brief summary: The purpose of this study is to evaluate the effect of the potent CYP3A4 inhibitor itraconazole on the single-dose PK of TAK-954.

Detailed description: 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).

Eligibility criteria: 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.

Primary outcomes:
measure: Cmax: Maximum Observed Plasma Concentration for TAK-954
timeFrame: 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
measure: AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-954
timeFrame: 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
Secondary outcomes:
Other outcomes:
Locations:
city: Lenexa
country: United States
facility: Pharmaceutical Research Associates, Inc.
state: Kansas
Study officials:
affiliation: Takeda
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: 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.