AzTrials
AzTrials

Healthy VolunteersPhase 1NCT03501069

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

A Phase 1 study testing TAK-418 in people with Healthy Volunteers, run by Millennium Pharmaceuticals, Inc. at 2 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 to 55 years, women onlyHealthy volunteers can take part
Conditions the study is for
Healthy Volunteers
What is being tested?
TAK-418
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
32 participants
Where
2 sitesUnited States
Study dates
30 May 2018to 26 Dec 2018
Phase
Phase 1
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 55 years
  • Women only
  • Healthy volunteers accepted
  • Adult

Who may be able to join

  • 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:
  • 1. Has a BMI >=18.0 and <= 26.0 kg/m^2, at the Screening Visit.

Who cannot join

  • 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.
Show all 19Show fewer
  • 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.
  • Has any abnormal finding on ophthalmological assessment/fundoscopy indicative of raised intracranial pressure (that is, optic disc swelling/edema; or [uncontrolled] hypertensive retinopathy).
  • Regularly has moderate-to-severe headaches requiring analgesics.
  • Has any bleeding abnormality or history of bleeding abnormalities.
  • Has abnormal coagulation tests (prothrombin time [PT]/international normalized ratio [INR], partial thromboplastin time [PTT]) at Screening.

Trial locations and contacts

2 sites in 1 country.

United States2 sites
  • Parexel International

    Glendale, California, 91206

  • PRA Health Sciences

    Salt Lake City, Utah, 84124

Other trials in United States

About this study

Official title: A Randomized, Double-Blind, Placebo-Controlled, Single and Multiple Oral Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of TAK-418 in Healthy Female Subjects

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.

Read the detailed description

The drug being tested in this study is called TAK-418. This study will assess the safety, tolerability, PK and PD of single and multiple rising doses of TAK-418 in healthy Japanese or non-Japanese females.

The study will enroll approximately 48 participants in 6 cohorts and each cohort will have 8 participants. The study will include 2 parts: single rising dose (SRD) in Cohort 1 and multiple rising dose (MRD) in Cohorts 2 to 6. Cohort 3 will include cerebrospinal fluid (CSF) collection. Participants will be randomly assigned (by chance, like flipping a coin) to one of the 6 cohorts.

This two-center trial will be conducted in the United States. The overall time to participate in Cohort 1 of this study is approximately 105 days and 98 days in Cohort 2. Participants will be contacted by telephone 14 days after last dose of study drug for a follow-up assessment.

Being tested
TAK-418, TAK-418 Matching Placebo
Keywords
Drug Therapy

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • TAK-418Drug

    TAK-418 capsules.

  • TAK-418 Matching PlaceboDrug

    TAK-418 matching placebo capsules.

Study groups in NCT03501069
Study groupRoleWhat they receive
Non-Japanese Cohort 1: TAK-418 120 mg and TAK-418 160 mgExperimentalTAK-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.
Receives: Drug: TAK-418; Drug: TAK-418 Matching Placebo
Non-Japanese Cohort 2: TAK-418 20 mgExperimentalTAK-418 20 mg or TAK-418 matching placebo, capsule, orally, once daily for 10 days.
Receives: Drug: TAK-418; Drug: TAK-418 Matching Placebo
Non-Japanese Cohort 3: TAK-418 40 mgExperimentalTAK-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.
Receives: Drug: TAK-418; Drug: TAK-418 Matching Placebo
Non-Japanese Cohort 4: TAK-418 60 mgExperimentalTAK-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.
Receives: Drug: TAK-418; Drug: TAK-418 Matching Placebo
Japanese Cohort 5: TAK-418 20 mgExperimentalTAK-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.
Receives: Drug: TAK-418; Drug: TAK-418 Matching Placebo
Japanese Cohort 6: TAK-418 40 mgExperimentalTAK-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.
Receives: Drug: TAK-418; Drug: TAK-418 Matching Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

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

    Measured: Baseline up to Day 60

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

    Measured: Baseline up to Day 70

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

    Measured: Baseline up to Day 60

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

    Measured: Baseline up to Day 70

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

    Measured: Baseline up to Day 60

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

    Measured: Baseline up to Day 70

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

    Measured: Baseline up to Day 60

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

    Measured: Baseline up to Day 70

Secondary outcomes (4)
  1. Cohort 1; AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-418 on Day 1

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

  2. 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

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

  3. Cmax: Maximum Observed Plasma Concentration for TAK-418

    Measured: 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

  4. Tmax: Time to Reach the Cmax for TAK-418

    Measured: 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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted18 Apr 2018
  2. Study start30 May 2018
  3. Primary completion26 Dec 2018
  4. Study completion26 Dec 2018

Why it stopped: Business Decision; no human safety concern; evaluating preclinical toxicology finding

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Other
Allocation
Randomised
Intervention model
Sequential
Masking
Triple blind
Who is masked
Participant, Investigator, Outcomes assessor
Enrolment
32 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03501069
Sponsor's protocol ID
TAK-418-1003
Other IDs
U1111-1209-4647
Status last verified
Jun 2020
First submitted
10 Apr 2018
Last updated
16 Jun 2020
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: Takeda makes patient-level, de-identified data sets and associated documents available for all interventional studies after applicable marketing approvals and commercial availability have been received (or program is completely terminated), an opportunity for the primary publication of the research and final report development has been allowed, and other criteria have been met as set forth in Takeda's Data Sharing Policy (see www.TakedaClinicalTrials.com 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.

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.

    PubMed 33990969

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing TAK-418 in people with Healthy Volunteers, run by Millennium Pharmaceuticals, Inc. at 2 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 16 Jun 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 16 Jun 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Cohort 1: Number of Participants Who Experienced at Least One Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Event (SAE) (time frame: Baseline up to Day 60). The study lists 8 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03501069, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Jun 2020.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in