A Study to Evaluate the Safety, Tolerability, Pharmacokinetics (PK), and Pharmacodynamics (PD) of Single and Multiple Oral Dose of TAK-418 in Healthy Female Participants

NCT03501069 | Terminated Phase 1 Results FDA Drug

• 2 other identifiers: TAK-418-1003U1111-1209-4647
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 2

Brief Summary

The purpose of this study is to characterize safety and tolerability of TAK-418 in non-Japanese and Japanese healthy female participants when administered at single or multiple (once daily \[QD\]) oral doses.

Conditions

Healthy Volunteers

Keywords

Drug Therapy

Outcome Measures

Primary Outcomes (8)

• Cohort 1: Number of Participants Who Experienced at Least One Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Event (SAE)

  Baseline up to Day 60

• Cohorts 2 to 5: Number of Participants Who Experienced at Least One TEAEs and SAE

  Baseline up to Day 70

• Cohort 1: Number of Participants With Markedly Abnormal Criteria for Clinical Laboratory Values at Least Once Postdose

  Baseline up to Day 60

• Cohorts 2 to 5: Number of Participants With Markedly Abnormal Criteria for Clinical Laboratory Values at Least Once Postdose

  Baseline up to Day 70

• Cohort 1: Number of Participants With Markedly Abnormal Criteria for Vital Signs at Least Once Postdose

  Baseline up to Day 60

• Cohorts 2 to 5: Number of Participants With Markedly Abnormal Criteria for Vital Signs at Least Once Postdose

  Baseline up to Day 70

• Cohort 1: Number of Participants Who Meet the Markedly Abnormal Values of 12-lead Electrocardiogram (ECG) Parameters at Least Once Post Dose

  Baseline up to Day 60

• Cohorts 2 to 5: Number of Participants Who Meet the Markedly Abnormal Values of 12-lead ECG Parameters at Least Once Post Dose

  Baseline up to Day 70

Secondary Outcomes (4)

• Cohort 1; AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-418 on Day 1

  Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose

• Cohort 2 to 5: AUCτ: Area Under the Plasma Concentration-time Curve From Time 0 to 24 Over the Dosing Interval for TAK-418 on Days 1 and 10

  Days 1 and 10 pre-dose and at multiple time points (up to 24 hours) post-dose

• Cmax: Maximum Observed Plasma Concentration for TAK-418

  Cohort 1: Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose; Cohorts 2 to 5: Days 1 and 10 pre-dose and at multiple time points (up to 48 hours) post-dose

• Tmax: Time to Reach the Cmax for TAK-418

  Cohort 1: Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose; Cohorts 2 to 5: Days 1 and 10 pre-dose and at multiple time points (up to 48 hours) post-dose

Study Arms (6)

Non-Japanese Cohort 1: TAK-418 120 mg and TAK-418 160 mg

EXPERIMENTAL

TAK-418 120 milligram (mg) or TAK-418 matching placebo, capsule, orally, once on Day 1 of Period A followed by a minimum of 14 days of washout period, followed by TAK-418 160 mg or TAK-418 matching placebo, capsule, orally, once on Day 1 of Period B. The actual TAK-418 dose for Period B will be determined based on safety, tolerability, and PK data available from the previous dose in Period A.

Drug: TAK-418; Drug: TAK-418 Matching Placebo

Non-Japanese Cohort 2: TAK-418 20 mg

EXPERIMENTAL

TAK-418 20 mg or TAK-418 matching placebo, capsule, orally, once daily for 10 days.

Drug: TAK-418; Drug: TAK-418 Matching Placebo

Non-Japanese Cohort 3: TAK-418 40 mg

EXPERIMENTAL

TAK-418 40 mg or TAK-418 matching placebo, capsule, orally, once daily for 10 days. The actual TAK-418 dose for Cohort 3 will be determined based on safety, tolerability, and PK data available from the previous doses.

Drug: TAK-418; Drug: TAK-418 Matching Placebo

Non-Japanese Cohort 4: TAK-418 60 mg

EXPERIMENTAL

TAK-418 60 mg or TAK-418 matching placebo, capsule, orally, once daily for 10 days. The actual TAK-418 dose for Cohort 4 will be determined based on safety, tolerability, and PK data available from the previous doses.

Drug: TAK-418; Drug: TAK-418 Matching Placebo

Japanese Cohort 5: TAK-418 20 mg

EXPERIMENTAL

TAK-418 20 mg or TAK-418 matching placebo, capsule, orally, once daily for 10 days. The actual TAK-418 dose for Cohort 5 will be determined based on safety, tolerability, and PK data available from the previous doses.

Drug: TAK-418; Drug: TAK-418 Matching Placebo

Japanese Cohort 6: TAK-418 40 mg

EXPERIMENTAL

TAK-418 40 mg or TAK-418 matching placebo, capsule, orally, once daily for 10 days. The actual TAK-418 dose for Cohort 6 will be determined based on safety, tolerability, and PK data available from the previous doses.

Drug: TAK-418; Drug: TAK-418 Matching Placebo

Interventions

TAK-418 DRUG

TAK-418 capsules.

Japanese Cohort 5: TAK-418 20 mg; Japanese Cohort 6: TAK-418 40 mg; Non-Japanese Cohort 1: TAK-418 120 mg and TAK-418 160 mg; Non-Japanese Cohort 2: TAK-418 20 mg; Non-Japanese Cohort 3: TAK-418 40 mg; Non-Japanese Cohort 4: TAK-418 60 mg

TAK-418 Matching Placebo DRUG

TAK-418 matching placebo capsules.

Japanese Cohort 5: TAK-418 20 mg; Japanese Cohort 6: TAK-418 40 mg; Non-Japanese Cohort 1: TAK-418 120 mg and TAK-418 160 mg; Non-Japanese Cohort 2: TAK-418 20 mg; Non-Japanese Cohort 3: TAK-418 40 mg; Non-Japanese Cohort 4: TAK-418 60 mg

Eligibility Criteria

• Age: 18 Years - 55 Years
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Has a body mass index (BMI) greater than or equal to (\>=) 18.5 and less than or equal to (\<=) 30.0 kilogram per square meter (kg/m\^2) at the Screening Visit. (Cohorts 1 to 4 only).
• Is a nonsmoker who has not used tobacco- or nicotine-containing products (example, nicotine patch) for at least 6 months before administration of the first dose of trial drug or invasive procedure.
• The participant either is of nonchildbearing potential, OR, if of childbearing potential, is using a highly effective method of contraception with low user dependency during the entire duration of the study.
• For Cohorts 5 and 6 (Japanese participants) only:
• \. Has a BMI \>=18.0 and \<= 26.0 kg/m\^2, at the Screening Visit.

You may not qualify if:

• Has a positive test result for hepatitis B surface antigen (HBsAg), hepatitis C antibody (HCV), or human immunodeficiency virus (HIV) antibody/antigen, at Screening.
• Had major surgery, donated or lost 1 unit of blood (approximately 500 milliliter \[mL\]) within 4 weeks before the Screening Visit.
• 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).
• 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.
• Has a substance abuse disorder.
• Has risk of suicide according to the investigator's clinical judgment per Columbia-Suicide Severity Rating Scale (C-SSRS) at Screening or has made a suicide attempt in the 6 months before Screening.
• Has luteinizing hormone (LH), follicle-stimulating hormone (FSH), or estradiol levels that are clinically abnormal.
• Has a resting heart rate outside of the range of 50 to 100 beats per minute, confirmed on repeat testing within a maximum of 30 minutes, at the Screening Visit or Check-in (Day -1).
• For Cohort 3 only (includes CSF sample collection):
• Has had CSF collection performed within 30 days before Check-in (Day -1).
• Has significant vertebral deformities (scoliosis or kyphosis) that, in the opinion of the investigator, may interfere with the lumbar puncture procedure.
• Has a local infection at the puncture site.
• Has thrombocytopenia or other suspected bleeding tendencies noted before the procedure.
• Has developed signs and symptoms of spinal radiculopathy, including lower extremity pain and paresthesia.
• Has any focal neurological deficit that might suggest an increase in intracranial pressure.

Sponsors & Collaborators

• Millennium Pharmaceuticals, Inc.: lead

Study Sites (2)

Parexel International

Glendale, California, 91206, United States

Location

PRA Health Sciences

Salt Lake City, Utah, 84124, United States

Location

Related Publications (1)

• 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.

  PMID: 33990969 DERIVED

MeSH Terms

Interventions

TAK-418

Results Point of Contact

• Title: Medical Director
• Organization: Takeda

trialdisclosures@takeda.com

+1-877-825-3327

Study Officials

• Medical Director

  Takeda

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: OTHER
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 10, 2018
• First Posted: April 18, 2018
• Study Start: May 30, 2018
• Primary Completion: December 26, 2018
• Study Completion: December 26, 2018
• Last Updated: June 16, 2020
• Results First Posted: June 16, 2020

Record last verified: 2020-06

Data Sharing

• IPD Sharing: Will share

Locations

US (2)