Clinical trial NCT03228433: A Study to Evaluate Safety, Tolerability and Pharmacokinetics of Ascending Oral Single Dose of TAK-418 in Healthy Participants
Official title: A Randomized, Double-Blind, Placebo-Controlled, Ascending Oral Single Dose Trial to Evaluate the Safety, Tolerability, and Pharmacokinetics of TAK-418 in Healthy Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Participants
Keywords: Drug Therapy
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2017-07-24
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: OTHER

Brief summary: The purpose of this study is to evaluate the safety and tolerability of TAK-418 following single oral doses in healthy participants.

Detailed description: The drug being tested in this study is called TAK-418. TAK-418 is being tested in healthy participants in order to evaluate the safety, tolerability, and pharmacokinetics (PK) of single oral doses.

The study will enroll approximately 40 healthy participants. The study consists of equally divided 5 sequential cohorts of 8 participants each. In each of the following cohorts, 6 participants will be randomized to receive TAK-418 and 2 participants will receive matching placebo-which will remain undisclosed to the participant and study doctor during the study (unless there is an urgent medical need):

* Cohort 1: TAK-418 5 mg
* Cohort 2: TAK-418 15 mg
* Cohort 3: TAK-418 30 mg Fasted + TAK-418 30 mg Fed
* Cohort 4: TAK-418 40 mg
* Cohort 5: TAK-418 60 mg

All participants will be asked to take TAK-418 or placebo-matching capsule once on Day 1 in each cohort. A washout period of 28-days will be maintained between the doses in Cohort 3.

This single center trial will be conducted in the United States. Participants in this study will be assigned to one of 5 possible dose cohorts. Male participants will return for additional outpatient visits on Days 91 and 93 (+/- 7 days) and may return for outpatient visits on Days 182 and 184 (+/- 7 days) (depending on results from the Day 93 Visit).

Eligibility criteria: Inclusion Criteria:

1. Is a male or female participants with a body mass index (BMI) within the range of 18.5 -30.0 kilogram per square meter (kg/m\^2) at the Screening Visit.
2. Is a nonsmoker who has not used tobacco or nicotine-containing products (example, nicotine patch) for at least 6 months before trial drug administration of the initial dose of trial drug or invasive procedure.
3. Must be judged to be in good health by the investigator, based on clinical evaluations including laboratory safety tests, medical history, physical examination, 12-lead ECG, and vital sign measurements performed at the Screening Visit and before administration of the initial dose of trial drug or invasive procedure as per principal investigator's judgment.
4. Female subjects with no childbearing potential, defined by at least 1 of the following criteria:

   * Postmenopausal (defined as 12 months of spontaneous amenorrhea in women aged greater than \[\>\]45 years, 6 months of spontaneous amenorrhea in women aged \>45 years with serum follicle-stimulating hormone \[FSH\] levels \>40 milli-international units per milliliter \[mIU/mL\]). Appropriate documentation of FSH levels is required.
   * Surgically sterile by hysterectomy and/or bilateral oophorectomy with appropriate documentation of surgical procedure.
   * Had a tubal ligation with appropriate documentation of surgical procedure.
   * Has a congenital condition resulting in no uterus.

Exclusion Criteria:

1. Has had major surgery, donated or lost 1 unit of blood (approximately 500 milliliter \[mL\]) within 4 weeks before the Screening Visit.
2. Has a risk of suicide according to the investigator's clinical judgment per the Columbia-Suicide Severity Rating Scale at Screening or has made a suicide attempt in the 6 months before Screening.

Primary outcomes:
measure: Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs)
timeFrame: Baseline Up to Day 184
measure: Number of Participants Who Discontinued Due to an Adverse Event (AE)
timeFrame: Baseline Up to Day 184
measure: Number of Participants Who Meet the Markedly Abnormal Criteria for Neurological Assessment Measurements at Least Once Post Dose
timeFrame: Baseline Up to Day 184
measure: Number of Participants Who Meet the Markedly Abnormal Criteria for Safety Laboratory Tests at Least Once Post Dose
timeFrame: Baseline Up to Day 184
measure: Number of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post Dose
timeFrame: Baseline Up to day 184
measure: Number of Participants Who Meet the Markedly Abnormal Criteria for Safety 12-lead Electrocardiogram (ECG) Parameters at Least Once Post Dose
timeFrame: Baseline Up to Day 14
Secondary outcomes:
measure: AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration of TAK-418F (TAK-418 Free Base)
timeFrame: Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose
measure: AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-418F
timeFrame: Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose
measure: Cmax: Maximum Observed Plasma Concentration for TAK-418F
timeFrame: Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose
measure: Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-418F
timeFrame: Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose
Other outcomes:
Locations:
city: Glendale
country: United States
facility: PAREXEL International
state: California
Study officials:
affiliation: Takeda
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: Yin W, Arkilo D, Khudyakov P, Hazel J, Gupta S, Quinton MS, Lin J, Hartman DS, Bednar MM, Rosen L, Wendland JR. Safety, pharmacokinetics and pharmacodynamics of TAK-418, a novel inhibitor of the epigenetic modulator lysine-specific demethylase 1A. Br J Clin Pharmacol. 2021 Dec;87(12):4756-4768. doi: 10.1111/bcp.14912. Epub 2021 Jun 10.