Healthy ParticipantsPhase 1NCT03228433
A Study to Evaluate Safety, Tolerability and Pharmacokinetics of Ascending Oral Single Dose of TAK-418 in Healthy Participants
A Phase 1 study testing TAK-418 in people with Healthy Participants, run by Takeda at 1 site in United States.
Trial summary
The purpose of this study is to evaluate the safety and tolerability of TAK-418 following single oral doses in healthy participants. Read more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Healthy Participants
- 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
- 40 participants
- Where
- 1 siteUnited States
- Study dates
- 21 Jul 2017to 12 May 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
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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.
- 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.
- 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.
- 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.
Who cannot join
- Has had major surgery, donated or lost 1 unit of blood (approximately 500 milliliter [mL]) within 4 weeks before the Screening Visit.
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
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
The purpose of this study is to evaluate the safety and tolerability of TAK-418 following single oral doses in healthy participants.
Read the 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).
- Conditions
- Healthy Participants
- Being tested
- TAK-418, TAK-418 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 Capsule.
TAK-418 PlaceboDrug
TAK-418 placebo-matching capsules.
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1: TAK-418 5 mg | Experimental | TAK-418 5 milligram (mg), capsule, orally, once on Day 1. Receives: Drug: TAK-418 |
| Cohort 2: TAK-418 15 mg | Experimental | 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. Receives: Drug: TAK-418 |
| Cohort 3: TAK-418 30 mg Fasted + TAK-418 30 mg Fed | Experimental | 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. Receives: Drug: TAK-418 |
| Cohort 4: TAK-418 40 mg | Experimental | 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. Receives: Drug: TAK-418 |
| Cohort 5: TAK-418 60 mg | Experimental | 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. Receives: Drug: TAK-418 |
| Cohorts 1-5: Placebo | Placebo comparator | TAK-418 placebo-matching, capsule, orally, once on Day 1. Receives: Drug: TAK-418 Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs)
Measured: Baseline Up to Day 184
Number of Participants Who Discontinued Due to an Adverse Event (AE)
Measured: Baseline Up to Day 184
Number of Participants Who Meet the Markedly Abnormal Criteria for Neurological Assessment Measurements at Least Once Post Dose
Measured: Baseline Up to Day 184
Number of Participants Who Meet the Markedly Abnormal Criteria for Safety Laboratory Tests at Least Once Post Dose
Measured: Baseline Up to Day 184
Number of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post Dose
Measured: 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
Measured: Baseline Up to Day 14
Secondary outcomes (4)
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)
Measured: 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
Measured: Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose
Cmax: Maximum Observed Plasma Concentration for TAK-418F
Measured: 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.
Measured: Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Jul 2017
- Study start21 Jul 2017
- Primary completion12 May 2018
- Study completion12 May 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Healthy ParticipantsStudies of the same condition, open and under way.
- More trials run by TakedaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 40 participants (actual)
Sponsor and investigators
- Lead sponsor
- Takeda
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Director, Study director, Takeda
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03228433
- Sponsor's protocol ID
- TAK-418-1001
- Other IDs
- U1111-1195-7777
- Status last verified
- Aug 2019
- First submitted
- 21 Jul 2017
- Last updated
- 9 Sep 2019
- Results posted
- Yes, on ClinicalTrials.gov
- 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 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.
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
Study at a glance
From the registry record, last updated by the sponsor on 9 Sep 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03228433
- Acronym / sponsor ID
- TAK-418-1001
- Conditions
- Healthy Participants
- Keywords
- Drug Therapy
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 40 participants (actual)
- Lead sponsor
- TakedaIndustry (pharma, biotech, devices)
- Study start
- 21 Jul 2017 (actual)
- Primary completion
- 12 May 2018 (actual)
- Study completion
- 12 May 2018 (actual)
- First posted
- 24 Jul 2017 (actual)
- Results
- Posted 9 Sep 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| Cohort 1: TAK-418 5 mg | Experimental | Drug: TAK-418TAK-418 5 milligram (mg), capsule, orally, once on Day 1. |
| Cohort 2: TAK-418 15 mg | Experimental | Drug: TAK-418TAK-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. |
| Cohort 3: TAK-418 30 mg Fasted + TAK-418 30 mg Fed | Experimental | Drug: TAK-418TAK-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. |
| Cohort 4: TAK-418 40 mg | Experimental | Drug: TAK-418TAK-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. |
| Cohort 5: TAK-418 60 mg | Experimental | Drug: TAK-418TAK-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. |
| Cohorts 1-5: Placebo | Placebo comparator | Drug: TAK-418 PlaceboTAK-418 placebo-matching, capsule, orally, once on Day 1. |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (8 listed)
- 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.
- 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.
- 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.
- Female subjects with no childbearing potential, defined by at least 1 of the following criteria:
Key exclusion criteria (2 listed)
- Has had major surgery, donated or lost 1 unit of blood (approximately 500 milliliter [mL]) within 4 weeks before the Screening Visit.
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TAK-418TAK-418 Capsule. | Drug | 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 |
| TAK-418 PlaceboTAK-418 placebo-matching capsules. | Drug | Cohorts 1-5: Placebo |
Primary outcome
Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs)
Time frame: Baseline Up to Day 184
Number of Participants Who Discontinued Due to an Adverse Event (AE)
Time frame: Baseline Up to Day 184
Number of Participants Who Meet the Markedly Abnormal Criteria for Neurological Assessment Measurements at Least Once Post Dose
Time frame: Baseline Up to Day 184
Number of Participants Who Meet the Markedly Abnormal Criteria for Safety Laboratory Tests at Least Once Post Dose
Time frame: Baseline Up to Day 184
Number of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post Dose
Time frame: 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
Time frame: Baseline Up to Day 14
4 secondary outcomes
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)
Time frame: 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
Time frame: Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose
Cmax: Maximum Observed Plasma Concentration for TAK-418F
Time frame: 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
Time frame: Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Sep 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 33990969Yin 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.
- Individual participant dataSharing planned: Yes. 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Medical Director study director
Takeda
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing TAK-418 in people with Healthy Participants, run by Takeda at 1 site 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 8 inclusion and 2 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: finished, as of the sponsor's last update on 9 Sep 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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. Some participants in this study may receive a placebo. 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 9 Sep 2019). 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?
Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) (time frame: Baseline Up to Day 184). The study lists 6 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 NCT03228433, 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 9 Sep 2019.