A Study to Evaluate Safety, Tolerability and Pharmacokinetics of Ascending Oral Single Dose of TAK-418 in Healthy Participants

A Randomized, Double-Blind, Placebo-Controlled, Ascending Oral Single Dose Trial to Evaluate the Safety, Tolerability, and Pharmacokinetics of TAK-418 in Healthy Subjects

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

Study Overview

• Status: Completed
• Conditions: Healthy Participants
• Intervention / Treatment: Drug: TAK-418; Drug: TAK-418 Placebo

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).

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Glendale, California, United States, 91206
      • PAREXEL International

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Quadruple

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1: TAK-418 5 mg; TAK-418 5 milligram (mg), capsule, orally, once on Day 1.	Drug: TAK-418; TAK-418 Capsule.
Experimental: Cohort 2: TAK-418 15 mg; TAK-418 15 mg, capsule, orally, once on Day 1. Actual dose of TAK-418 may vary based on safety, tolerability and PK data from previous Cohorts.	Drug: TAK-418; TAK-418 Capsule.
Experimental: Cohort 3: TAK-418 30 mg Fasted + TAK-418 30 mg Fed; TAK-418 30 mg, capsule, in fasted state, orally, once on Day 1, followed by a 28-day washout period, further followed by TAK-418 30 mg, capsule, in fed state, orally, once on Day 1. Actual dose of TAK-418 may vary based on safety, tolerability and PK data from previous Cohorts.	Drug: TAK-418; TAK-418 Capsule.
Experimental: Cohort 4: TAK-418 40 mg; TAK-418 40 mg, capsule, orally, once on Day 1. Actual dose of TAK-418 may vary based on safety, tolerability and PK data from previous Cohorts.	Drug: TAK-418; TAK-418 Capsule.
Experimental: Cohort 5: TAK-418 60 mg; TAK-418 60 mg, capsule, orally, once on Day 1. Actual dose of TAK-418 may vary based on safety, tolerability and PK data from previous Cohorts.	Drug: TAK-418; TAK-418 Capsule.
Placebo Comparator: Cohorts 1-5: Placebo; TAK-418 placebo-matching, capsule, orally, once on Day 1.	Drug: TAK-418 Placebo; TAK-418 placebo-matching capsules.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs)	Baseline Up to Day 184
Number of Participants Who Discontinued Due to an Adverse Event (AE)	Baseline Up to Day 184
Number of Participants Who Meet the Markedly Abnormal Criteria for Neurological Assessment Measurements at Least Once Post Dose	Baseline Up to Day 184
Number of Participants Who Meet the Markedly Abnormal Criteria for Safety Laboratory Tests at Least Once Post Dose	Baseline Up to Day 184
Number of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post Dose	Baseline Up to day 184
Number of Participants Who Meet the Markedly Abnormal Criteria for Safety 12-lead Electrocardiogram (ECG) Parameters at Least Once Post Dose	Baseline Up to Day 14

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)		Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose
AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-418F		Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose
Cmax: Maximum Observed Plasma Concentration for TAK-418F		Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose
Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-418F	The pharmacokinetic analysis set included all participants who received at least 1 dose of study drug and had at least one measurable plasma concentration or amount of drug in urine for TAK-418-F.	Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose

Collaborators and Investigators

• Sponsor: Takeda

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): July 21, 2017
• Primary Completion (Actual): May 12, 2018
• Study Completion (Actual): May 12, 2018

Study Registration Dates

• First Submitted: July 21, 2017
• First Submitted That Met QC Criteria: July 21, 2017
• First Posted (Actual): July 24, 2017

Study Record Updates

• Last Update Posted (Actual): September 9, 2019
• Last Update Submitted That Met QC Criteria: August 9, 2019
• Last Verified: August 1, 2019

More Information

Terms related to this study

• Keywords: Drug Therapy
• Other Study ID Numbers: TAK-418-1001; U1111-1195-7777 (Registry Identifier: WHO)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Takeda makes patient-level, de-identified data sets and associated documents available after applicable marketing approvals and commercial availability have been received, an opportunity for the primary publication of the research has been allowed, and other criteria have been met as set forth in Takeda's Data Sharing Policy (see www.TakedaClinicalTrials.com/Approach for details). To obtain access, researchers must submit a legitimate academic research proposal for adjudication by an independent review panel, who will review the scientific merit of the research and the requestor's qualifications and conflict of interest that can result in potential bias. Once approved, qualified researchers who sign a data sharing agreement are provided access to these data in a secure research environment.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No