A Study to Evaluate Safety, Tolerability and Pharmacokinetics of Ascending Oral Single Dose of TAK-418 in Healthy Participants
Sponsor
Takeda (Industry)
Overall Status
Completed
CT.gov ID
NCT03228433
Collaborator
(none)
40
1
6
9.7
4.1
Study Details
Study Description
Brief Summary
The purpose of this study is to evaluate the safety and tolerability of TAK-418 following single oral doses in healthy participants.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
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
Study Type:
Interventional
Actual Enrollment
:
40 participants
Allocation:
Randomized
Intervention Model:
Sequential Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Other
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
Actual Study Start Date
:
Jul 21, 2017
Actual Primary Completion Date
:
May 12, 2018
Actual Study Completion Date
:
May 12, 2018
Arms and Interventions
| 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.
|
Outcome Measures
Primary Outcome Measures
- 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
- 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 [Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose]
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.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
to 55 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
Yes
Inclusion Criteria:
-
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.
Exclusion Criteria:
-
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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | PAREXEL International | Glendale | California | United States | 91206 |
Sponsors and Collaborators
- Takeda
Investigators
- Study Director: Medical Director, Takeda
Study Documents (Full-Text)
More Information
Publications
None provided.Responsible Party:
Takeda
ClinicalTrials.gov Identifier:
NCT03228433
Other Study ID Numbers:
- TAK-418-1001
- U1111-1195-7777
First Posted:
Jul 24, 2017
Last Update Posted:
Sep 9, 2019
Last Verified:
Aug 1, 2019
Individual Participant Data (IPD) Sharing Statement:
Yes
Plan to Share IPD:
Yes
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by Takeda
Study Results
Participant Flow
| Recruitment Details | Participants took part in the study at single site in the United States from 21 July 2017 to 12 May 2018. |
|---|---|
| Pre-assignment Detail | Healthy participants were randomized to receive TAK-418 or matching placebo in Cohorts 1 to 5. |
| Arm/Group Title | Cohorts 1-5: Placebo | 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 |
|---|---|---|---|---|---|---|
| Arm/Group Description | TAK-418 placebo-matching, capsule, orally, once on Day 1. | TAK-418 5 milligram (mg), capsule, orally, once on Day 1. | TAK-418 15 mg, capsule, orally, once on Day 1. | 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. | TAK-418 40 mg, capsule, orally, once on Day 1. | TAK-418 60 mg, capsule, orally, once on Day 1. |
| Period Title: Overall Study | ||||||
| STARTED | 10 | 6 | 6 | 6 | 6 | 6 |
| COMPLETED | 9 | 6 | 6 | 5 | 6 | 6 |
| NOT COMPLETED | 1 | 0 | 0 | 1 | 0 | 0 |
Baseline Characteristics
| Arm/Group Title | Cohorts 1-5: Placebo | 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 | Total |
|---|---|---|---|---|---|---|---|
| Arm/Group Description | TAK-418 placebo-matching, capsule, orally, once on Day 1. | TAK-418 5 mg, capsule, orally, once on Day 1. | TAK-418 15 mg, capsule, orally, once on Day 1. | 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. | TAK-418 40 mg, capsule, orally, once on Day 1. | TAK-418 60 mg, capsule, orally, once on Day 1. | Total of all reporting groups |
| Overall Participants | 10 | 6 | 6 | 6 | 6 | 6 | 40 |
| Age (years) [Mean (Standard Deviation) ] | |||||||
| Mean (Standard Deviation) [years] |
36.4
(9.63)
|
37.2
(10.42)
|
33.3
(10.80)
|
40.0
(10.60)
|
33.2
(6.49)
|
38.7
(10.03)
|
36.5
(9.43)
|
| Sex: Female, Male (Count of Participants) | |||||||
| Female |
2
20%
|
2
33.3%
|
0
0%
|
1
16.7%
|
0
0%
|
3
50%
|
8
20%
|
| Male |
8
80%
|
4
66.7%
|
6
100%
|
5
83.3%
|
6
100%
|
3
50%
|
32
80%
|
| Ethnicity (NIH/OMB) (Count of Participants) | |||||||
| Hispanic or Latino |
1
10%
|
2
33.3%
|
2
33.3%
|
0
0%
|
1
16.7%
|
1
16.7%
|
7
17.5%
|
| Not Hispanic or Latino |
9
90%
|
4
66.7%
|
4
66.7%
|
6
100%
|
5
83.3%
|
5
83.3%
|
33
82.5%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Race (NIH/OMB) (Count of Participants) | |||||||
| American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
16.7%
|
0
0%
|
1
2.5%
|
| Asian |
1
10%
|
1
16.7%
|
2
33.3%
|
1
16.7%
|
1
16.7%
|
0
0%
|
6
15%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
16.7%
|
1
2.5%
|
| Black or African American |
5
50%
|
1
16.7%
|
1
16.7%
|
0
0%
|
2
33.3%
|
0
0%
|
9
22.5%
|
| White |
4
40%
|
4
66.7%
|
3
50%
|
4
66.7%
|
2
33.3%
|
5
83.3%
|
22
55%
|
| More than one race |
0
0%
|
0
0%
|
0
0%
|
1
16.7%
|
0
0%
|
0
0%
|
1
2.5%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Region of Enrollment (Count of Participants) | |||||||
| United States |
10
100%
|
6
100%
|
6
100%
|
6
100%
|
6
100%
|
6
100%
|
40
100%
|
| Weight (kilogram (kg)) [Mean (Standard Deviation) ] | |||||||
| Mean (Standard Deviation) [kilogram (kg)] |
81.2
(12.34)
|
76.0
(13.58)
|
81.8
(6.83)
|
82.5
(4.22)
|
80.0
(12.43)
|
76.1
(15.23)
|
79.8
(11.0)
|
| Height (centimeter (cm)) [Mean (Standard Deviation) ] | |||||||
| Mean (Standard Deviation) [centimeter (cm)] |
173.4
(8.66)
|
171.0
(8.10)
|
174.8
(3.19)
|
172.5
(5.09)
|
181.2
(5.08)
|
171.5
(11.78)
|
174.0
(7.89)
|
| Body mass index (BMI) (kilogram per square meter (kg/m^2)) [Mean (Standard Deviation) ] | |||||||
| Mean (Standard Deviation) [kilogram per square meter (kg/m^2)] |
26.94
(3.065)
|
25.82
(2.440)
|
26.83
(2.835)
|
27.83
(2.414)
|
24.32
(2.988)
|
25.73
(2.992)
|
26.32
(2.864)
|
Outcome Measures
| Title | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) |
|---|---|
| Description | |
| Time Frame | Baseline Up to Day 184 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The safety analysis set included all randomized participants who received at least 1 dose of study drug. |
| Arm/Group Title | Cohorts 1-5: Placebo | Cohort 1: TAK-418 5 mg | Cohort 2: TAK-418 15 mg | Cohort 3A: TAK-418 30 mg Fasted | Cohort 3B: TAK-418 30 mg Fed | Cohort 4: TAK-418 40 mg | Cohort 5: TAK-418 60 mg |
|---|---|---|---|---|---|---|---|
| Arm/Group Description | TAK-418 placebo-matching, capsule, orally, once on Day 1. | TAK-418 5 mg, capsule, orally, once on Day 1. | TAK-418 15 mg, capsule, orally, once on Day 1. | TAK-418 30 mg, capsule, in fasted state, orally, once on Day 1. | TAK-418 30 mg, capsule, in fed state, orally, once on Day 1. | TAK-418 40 mg, capsule, orally, once on Day 1. | TAK-418 60 mg, capsule, orally, once on Day 1. |
| Measure Participants | 10 | 6 | 6 | 6 | 5 | 6 | 6 |
| Number [participants] |
4
40%
|
2
33.3%
|
2
33.3%
|
3
50%
|
1
16.7%
|
3
50%
|
3
7.5%
|
| Title | Number of Participants Who Discontinued Due to an Adverse Event (AE) |
|---|---|
| Description | |
| Time Frame | Baseline Up to Day 184 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The safety analysis set included all randomized participants who received at least 1 dose of study drug. |
| Arm/Group Title | Cohorts 1-5: Placebo | Cohort 1: TAK-418 5 mg | Cohort 2: TAK-418 15 mg | Cohort 3A: TAK-418 30 mg Fasted | Cohort 3B: TAK-418 30 mg Fed | Cohort 4: TAK-418 40 mg | Cohort 5: TAK-418 60 mg |
|---|---|---|---|---|---|---|---|
| Arm/Group Description | TAK-418 placebo-matching, capsule, orally, once on Day 1. | TAK-418 5 mg, capsule, orally, once on Day 1. | TAK-418 15 mg, capsule, orally, once on Day 1. | TAK-418 30 mg, capsule, in fasted state, orally, once on Day 1. | TAK-418 30 mg, capsule, in fed state, orally, once on Day 1. | TAK-418 40 mg, capsule, orally, once on Day 1. | TAK-418 60 mg, capsule, orally, once on Day 1. |
| Measure Participants | 10 | 6 | 6 | 6 | 5 | 6 | 6 |
| Number [participants] |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Title | Number of Participants Who Meet the Markedly Abnormal Criteria for Neurological Assessment Measurements at Least Once Post Dose |
|---|---|
| Description | |
| Time Frame | Baseline Up to Day 184 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The safety analysis set included all randomized participants who received at least 1 dose of study drug. |
| Arm/Group Title | Cohorts 1-5: Placebo | Cohort 1: TAK-418 5 mg | Cohort 2: TAK-418 15 mg | Cohort 3A: TAK-418 30 mg Fasted | Cohort 3B: TAK-418 30 mg Fed | Cohort 4: TAK-418 40 mg | Cohort 5: TAK-418 60 mg |
|---|---|---|---|---|---|---|---|
| Arm/Group Description | TAK-418 placebo-matching, capsule, orally, once on Day 1. | TAK-418 5 mg, capsule, orally, once on Day 1. | TAK-418 15 mg, capsule, orally, once on Day 1. | TAK-418 30 mg, capsule, in fasted state, orally, once on Day 1. | TAK-418 30 mg, capsule, in fed state, orally, once on Day 1. | TAK-418 40 mg, capsule, orally, once on Day 1. | TAK-418 60 mg, capsule, orally, once on Day 1. |
| Measure Participants | 10 | 6 | 6 | 6 | 5 | 6 | 6 |
| Number [participants] |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Title | Number of Participants Who Meet the Markedly Abnormal Criteria for Safety Laboratory Tests at Least Once Post Dose |
|---|---|
| Description | |
| Time Frame | Baseline Up to Day 184 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The safety analysis set included all randomized participants who received at least 1 dose of study drug. |
| Arm/Group Title | Cohorts 1-5: Placebo | Cohort 1: TAK-418 5 mg | Cohort 2: TAK-418 15 mg | Cohort 3A: TAK-418 30 mg Fasted | Cohort 3B: TAK-418 30 mg Fed | Cohort 4: TAK-418 40 mg | Cohort 5: TAK-418 60 mg |
|---|---|---|---|---|---|---|---|
| Arm/Group Description | TAK-418 placebo-matching, capsule, orally, once on Day 1. | TAK-418 5 mg, capsule, orally, once on Day 1. | TAK-418 15 mg, capsule, orally, once on Day 1. | TAK-418 30 mg, capsule, in fasted state, orally, once on Day 1. | TAK-418 30 mg, capsule, in fed state, orally, once on Day 1. | TAK-418 40 mg, capsule, orally, once on Day 1. | TAK-418 60 mg, capsule, orally, once on Day 1. |
| Measure Participants | 10 | 6 | 6 | 6 | 5 | 6 | 6 |
| Number [participants] |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Title | Number of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post Dose |
|---|---|
| Description | |
| Time Frame | Baseline Up to day 184 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The safety analysis set included all randomized participants who received at least 1 dose of study drug. |
| Arm/Group Title | Cohorts 1-5: Placebo | Cohort 1: TAK-418 5 mg | Cohort 2: TAK-418 15 mg | Cohort 3A: TAK-418 30 mg Fasted | Cohort 3B: TAK-418 30 mg Fed | Cohort 4: TAK-418 40 mg | Cohort 5: TAK-418 60 mg |
|---|---|---|---|---|---|---|---|
| Arm/Group Description | TAK-418 placebo-matching, capsule, orally, once on Day 1. | TAK-418 5 mg, capsule, orally, once on Day 1. | TAK-418 15 mg, capsule, orally, once on Day 1. | TAK-418 30 mg, capsule, in fasted state, orally, once on Day 1. | TAK-418 30 mg, capsule, in fed state, orally, once on Day 1. | TAK-418 40 mg, capsule, orally, once on Day 1. | TAK-418 60 mg, capsule, orally, once on Day 1. |
| Measure Participants | 10 | 6 | 6 | 6 | 5 | 6 | 6 |
| Diastolic blood pressure less than (<) 50 mmHg |
0
0%
|
1
16.7%
|
1
16.7%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Systolic blood pressure < 85 mmHg |
0
0%
|
0
0%
|
1
16.7%
|
0
0%
|
1
16.7%
|
0
0%
|
0
0%
|
| Temperature < 35.6 degrees celsius (°C) |
0
0%
|
0
0%
|
0
0%
|
1
16.7%
|
1
16.7%
|
1
16.7%
|
0
0%
|
| Temperature greater than (>) 37.7 (°C) |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
2
5%
|
| Title | Number of Participants Who Meet the Markedly Abnormal Criteria for Safety 12-lead Electrocardiogram (ECG) Parameters at Least Once Post Dose |
|---|---|
| Description | |
| Time Frame | Baseline Up to Day 14 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Cohorts 1-5: Placebo | Cohort 1: TAK-418 5 mg | Cohort 2: TAK-418 15 mg | Cohort 3A: TAK-418 30 mg Fasted | Cohort 3B: TAK-418 30 mg Fed | Cohort 4: TAK-418 40 mg | Cohort 5: TAK-418 60 mg |
|---|---|---|---|---|---|---|---|
| Arm/Group Description | TAK-418 placebo-matching, capsule, orally, once on Day 1. | TAK-418 5 mg, capsule, orally, once on Day 1. | TAK-418 15 mg, capsule, orally, once on Day 1. | TAK-418 30 mg, capsule, in fasted state, orally, once on Day 1. | TAK-418 30 mg, capsule, in fed state, orally, once on Day 1. | TAK-418 40 mg, capsule, orally, once on Day 1. | TAK-418 60 mg, capsule, orally, once on Day 1. |
| Measure Participants | 10 | 6 | 6 | 6 | 5 | 6 | 6 |
| ECG ventricular rate(Beats/ minute) |
1
10%
|
2
33.3%
|
1
16.7%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| QT interval (Milliseconds) |
0
0%
|
1
16.7%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
2.5%
|
| Title | 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) |
|---|---|
| Description | |
| Time Frame | Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | Cohort 1: TAK-418 5 mg | Cohort 2: TAK-418 15 mg | Cohort 3A: TAK-418 30 mg Fasted | Cohort 3B: TAK-418 30 mg Fed | Cohort 4: TAK-418 40 mg | Cohort 5: TAK-418 60 mg |
|---|---|---|---|---|---|---|
| Arm/Group Description | TAK-418 5 mg, capsule, orally, once on Day 1. | TAK-418 15 mg, capsule, orally, once on Day 1. | TAK-418 30 mg, capsule, in fasted state, orally, once on Day 1. | TAK-418 30 mg, capsule, in fed state, orally, once on Day 1. | TAK-418 40 mg, capsule, orally, once on Day 1. | TAK-418 60 mg, capsule, orally, once on Day 1. |
| Measure Participants | 6 | 6 | 6 | 5 | 6 | 6 |
| Geometric Mean (Geometric Coefficient of Variation) [hour nanogram per milliliter (h*ng/mL)] |
77.3
(47.1)
|
290.4
(21.8)
|
649.4
(8.5)
|
616.2
(23.1)
|
674.1
(27.0)
|
1576.3
(33.5)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Cohort 2: TAK-418 15 mg, Cohort 3A: TAK-418 30 mg Fasted |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Equivalence | |
| Comments | A linear mixed effect model on the natural log-transformed parameters was performed with a fixed effect for regimen and random effect for participant. The least squares(LS) means and difference of least squares (LS) means for the log-transformed parameters were exponentiated to obtain the point estimates (Geometric LS means) of the food effect and 90% confidence intervals (CIs). | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Least Squares (LS) Mean Difference |
| Estimated Value | 0.951 | |
| Confidence Interval |
(2-Sided) 90% 0.823 to 1.099 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Cohorts 1-5: Placebo, Cohort 1: TAK-418 5 mg, Cohort 2: TAK-418 15 mg, Cohort 3B: TAK-418 30 mg Fed, Cohort 4: TAK-418 40 mg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Equivalence | |
| Comments | A linear regression model (power model), log (ln) (parameter) equal to (=) intercept plus (+) slope*ln (dose), was fit to describe the relationship between each parameter and the corresponding dose levels. Dose Proportionality was declared if the 90% CI of the slope lied entirely within the critical region as defined by 1 - ln(0.8) per (/)l n(r) to 1 + ln(1.25)/ln(r), where r was the ratio of the highest and lowest dose in the study. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Slope |
| Estimated Value | 1.14 | |
| Confidence Interval |
(2-Sided) 90% 1.04 to 1.25 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-418F |
|---|---|
| Description | |
| Time Frame | Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | Cohort 1: TAK-418 5 mg | Cohort 2: TAK-418 15 mg | Cohort 3A: TAK-418 30 mg Fasted | Cohort 3B: TAK-418 30 mg Fed | Cohort 4: TAK-418 40 mg | Cohort 5: TAK-418 60 mg |
|---|---|---|---|---|---|---|
| Arm/Group Description | TAK-418 5 mg, capsule, orally, once on Day 1. | TAK-418 15 mg, capsule, orally, once on Day 1. | TAK-418 30 mg, capsule, in fasted state, orally, once on Day 1. | TAK-418 30 mg, capsule, in fed state, orally, once on Day 1. | TAK-418 40 mg, capsule, orally, once on Day 1. | TAK-418 60 mg, capsule, orally, once on Day 1. |
| Measure Participants | 6 | 6 | 6 | 5 | 6 | 6 |
| Geometric Mean (Geometric Coefficient of Variation) [h*ng/mL] |
84.9
(47.4)
|
296.3
(22.1)
|
659.6
(8.0)
|
626.0
(22.7)
|
681.0
(26.9)
|
1519.9
(33.3)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Cohort 2: TAK-418 15 mg, Cohort 3A: TAK-418 30 mg Fasted |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Equivalence | |
| Comments | Bioequivalence interval of 627.51 to 659.59 | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | 0.951 | |
| Confidence Interval |
(2-Sided) 90% 0.825 to 1.097 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Cohorts 1-5: Placebo, Cohort 1: TAK-418 5 mg, Cohort 2: TAK-418 15 mg, Cohort 3B: TAK-418 30 mg Fed, Cohort 4: TAK-418 40 mg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Equivalence | |
| Comments | A linear regression model (power model), ln (parameter) = intercept + slope*ln (dose), was fit to describe the relationship between each parameter and the corresponding dose levels. Dose Proportionality was declared if the 90% CI of the slope lied entirely within the critical region as defined by 1 - ln (0.8)/l n(r) to 1 + ln (1.25)/ln(r), where r was the ratio of the highest and lowest dose in the study. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Slope |
| Estimated Value | 1.11 | |
| Confidence Interval |
(2-Sided) 90% 1.00 to 1.22 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Cmax: Maximum Observed Plasma Concentration for TAK-418F |
|---|---|
| Description | |
| Time Frame | Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | Cohort 1: TAK-418 5 mg | Cohort 2: TAK-418 15 mg | Cohort 3A: TAK-418 30 mg Fasted | Cohort 3B: TAK-418 30 mg Fed | Cohort 4: TAK-418 40 mg | Cohort 5: TAK-418 60 mg |
|---|---|---|---|---|---|---|
| Arm/Group Description | TAK-418 5 mg, capsule, orally, once on Day 1. | TAK-418 15 mg, capsule, orally, once on Day 1. | TAK-418 30 mg, capsule, in fasted state, orally, once on Day 1. | TAK-418 30 mg, capsule, in fed state, orally, once on Day 1. | TAK-418 40 mg, capsule, orally, once on Day 1. | TAK-418 60 mg, capsule, orally, once on Day 1. |
| Measure Participants | 6 | 6 | 6 | 5 | 6 | 6 |
| Geometric Mean (Geometric Coefficient of Variation) [nanogram per millilitre (ng/mL)] |
21.54
(35.9)
|
61.90
(26.6)
|
163.64
(20.9)
|
94.93
(33.8)
|
155.32
(34.3)
|
321.52
(14.1)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Cohort 2: TAK-418 15 mg, Cohort 3A: TAK-418 30 mg Fasted |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Equivalence | |
| Comments | A linear mixed effect model on the natural log-transformed parameters was performed with a fixed effect for regimen and random effect for participant. The LS means and difference of LS means for the log-transformed parameters were exponentiated to obtain the point estimates (Geometric LS means) of the food effect and 90% confidence intervals CIs. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | 0.580 | |
| Confidence Interval |
(2-Sided) 90% 0.431 to 0.781 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Cohorts 1-5: Placebo, Cohort 1: TAK-418 5 mg, Cohort 2: TAK-418 15 mg, Cohort 3B: TAK-418 30 mg Fed, Cohort 4: TAK-418 40 mg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Equivalence | |
| Comments | A linear regression model (power model), ln (parameter) = intercept + slope*ln (dose), was fit to describe the relationship between each parameter and the corresponding dose levels. Dose Proportionality was declared if the 90% CI of the slope lied entirely within the critical region as defined by 1 - ln (0.8)/l n(r) to 1 + ln (1.25)/ln(r), where r was the ratio of the highest and lowest dose in the study. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Slope |
| Estimated Value | 1.06 | |
| Confidence Interval |
() 90% 0.96 to 1.17 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-418F |
|---|---|
| Description | 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. |
| Time Frame | Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Cohort 1: TAK-418 5 mg | Cohort 2: TAK-418 15 mg | Cohort 3A: TAK-418 30 mg Fasted | Cohort 3B: TAK-418 30 mg Fed | Cohort 4: TAK-418 40 mg | Cohort 5: TAK-418 60 mg |
|---|---|---|---|---|---|---|
| Arm/Group Description | TAK-418 5 mg, capsule, orally, once on Day 1. | TAK-418 15 mg, capsule, orally, once on Day 1. | TAK-418 30 mg, capsule, in fasted state, orally, once on Day 1. | TAK-418 30 mg, capsule, in fed state, orally, once on Day 1. | TAK-418 40 mg, capsule, orally, once on Day 1. | TAK-418 60 mg, capsule, orally, once on Day 1. |
| Measure Participants | 6 | 6 | 6 | 5 | 6 | 6 |
| Median (Full Range) [hour] |
1.000
|
1.000
|
1.000
|
3.000
|
1.250
|
1.000
|
Adverse Events
| Time Frame | Treatment-emergent adverse events are adverse events that started after the first dose of the study drug up to Day 184 | |||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. | |||||||||||||
| Arm/Group Title | Cohorts 1-5: Placebo | Cohort 1: TAK-418 5 mg | Cohort 2: TAK-418 15 mg | Cohort 3A: TAK-418 30 mg Fasted | Cohort 3B: TAK-418 30 mg Fed | Cohort 4: TAK-418 40 mg | Cohort 5: TAK-418 60 mg | |||||||
| Arm/Group Description | TAK-418 placebo-matching, capsule, orally, once on Day 1. | TAK-418 5 mg, capsule, orally, once on Day 1. | TAK-418 15 mg, capsule, orally, once on Day 1. | TAK-418 30 mg, capsule, in fasted state, orally, once on Day 1. | TAK-418 30 mg, capsule, in fed state, orally, once on Day 1. | TAK-418 40 mg, capsule, orally, once on Day 1. | TAK-418 60 mg, capsule, orally, once on Day 1. | |||||||
All Cause Mortality |
||||||||||||||
| Cohorts 1-5: Placebo | Cohort 1: TAK-418 5 mg | Cohort 2: TAK-418 15 mg | Cohort 3A: TAK-418 30 mg Fasted | Cohort 3B: TAK-418 30 mg Fed | Cohort 4: TAK-418 40 mg | Cohort 5: TAK-418 60 mg | ||||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/10 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/6 (0%) | |||||||
Serious Adverse Events |
||||||||||||||
| Cohorts 1-5: Placebo | Cohort 1: TAK-418 5 mg | Cohort 2: TAK-418 15 mg | Cohort 3A: TAK-418 30 mg Fasted | Cohort 3B: TAK-418 30 mg Fed | Cohort 4: TAK-418 40 mg | Cohort 5: TAK-418 60 mg | ||||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/10 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/6 (0%) | |||||||
Other (Not Including Serious) Adverse Events |
||||||||||||||
| Cohorts 1-5: Placebo | Cohort 1: TAK-418 5 mg | Cohort 2: TAK-418 15 mg | Cohort 3A: TAK-418 30 mg Fasted | Cohort 3B: TAK-418 30 mg Fed | Cohort 4: TAK-418 40 mg | Cohort 5: TAK-418 60 mg | ||||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 4/10 (40%) | 2/6 (33.3%) | 2/6 (33.3%) | 3/6 (50%) | 1/5 (20%) | 3/6 (50%) | 3/6 (50%) | |||||||
| Eye disorders | ||||||||||||||
| Eye irritation | 0/10 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/6 (0%) | |||||||
| Gastrointestinal disorders | ||||||||||||||
| Nausea | 0/10 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/5 (0%) | 1/6 (16.7%) | 0/6 (0%) | |||||||
| Dental caries | 0/10 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 1/6 (16.7%) | 0/6 (0%) | |||||||
| Vomiting | 0/10 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/6 (0%) | |||||||
| Abdominal pain | 1/10 (10%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/6 (0%) | |||||||
| Infections and infestations | ||||||||||||||
| Upper respiratory tract infection | 0/10 (0%) | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/5 (0%) | 0/6 (0%) | 2/6 (33.3%) | |||||||
| Musculoskeletal and connective tissue disorders | ||||||||||||||
| Groin pain | 0/10 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 1/6 (16.7%) | 0/6 (0%) | |||||||
| Limb discomfort | 0/10 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/6 (0%) | |||||||
| Muscle spasms | 1/10 (10%) | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/6 (0%) | |||||||
| Back pain | 0/10 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/6 (0%) | |||||||
| Arthralgia | 0/10 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/5 (20%) | 0/6 (0%) | 0/6 (0%) | |||||||
| Nervous system disorders | ||||||||||||||
| Headache | 1/10 (10%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 1/6 (16.7%) | 0/6 (0%) | |||||||
| Dizziness | 0/10 (0%) | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 1/5 (20%) | 0/6 (0%) | 0/6 (0%) | |||||||
| Somnolence | 1/10 (10%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 1/6 (16.7%) | |||||||
| Reproductive system and breast disorders | ||||||||||||||
| Testicular pain | 0/10 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/5 (0%) | 1/6 (16.7%) | 0/6 (0%) | |||||||
| Erectile dysfunction | 0/10 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 1/6 (16.7%) | 0/6 (0%) | |||||||
| Respiratory, thoracic and mediastinal disorders | ||||||||||||||
| Nasal congestion | 1/10 (10%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/6 (0%) | |||||||
| Skin and subcutaneous tissue disorders | ||||||||||||||
| Dermatitis contact | 1/10 (10%) | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/5 (0%) | 0/6 (0%) | 0/6 (0%) | |||||||
| Dry skin | 0/10 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/6 (0%) | |||||||
| Night sweats | 0/10 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/6 (0%) | |||||||
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
Research Organization shall not publish any articles or papers nor make any presentations, nor assist any other person in publishing any articles or papers or in making any presentations relating or referring to the Study or any results, data or insights from or any data, information or materials obtained or generated in the performance of its obligations without the prior written consent of Takeda, which consent may be granted or withheld in Takeda's sole discretion .
Results Point of Contact
| Name/Title | Medical Director |
|---|---|
| Organization | Takeda |
| Phone | +1-877-825-3327 |
| trialdisclosures@takeda.com |
Responsible Party:
Takeda
ClinicalTrials.gov Identifier:
NCT03228433
Other Study ID Numbers:
- TAK-418-1001
- U1111-1195-7777
First Posted:
Jul 24, 2017
Last Update Posted:
Sep 9, 2019
Last Verified:
Aug 1, 2019