A Pharmacokinetic Study of TAK-438 in Healthy Adult Chinese Participants
Sponsor
Takeda (Industry)
Overall Status
Completed
CT.gov ID
NCT03085836
Collaborator
(none)
33
1
3
3.9
8.4
Study Details
Study Description
Brief Summary
The purpose of this study is to determine the pharmacokinetics (PK) of TAK-438 in healthy adult Chinese participants after both single and multiple dose administration.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1 |
Detailed Description
The drug being tested in this study is called TAK-438. TAK-438 is being tested in healthy participants in order to evaluate the PK of single and multiple oral dose.
The study will enroll approximately 36 healthy participants. Participants will be assigned to one of the three treatment groups:
-
TAK-438 10 mg tablet once daily
-
TAK-438 20 mg tablet once daily
-
TAK-438 20 mg tablet twice daily All participants will be asked to take TAK-438 tablet at the same time on Day 1 and Days 3-9.
This single-centre trial will be conducted in China. The overall time to participate in this study is 18 days. Participants will remain confined to the clinic from Day 1 up to Day 11 and will be followed-up by telephone or visit on Day 18.
Study Design
Study Type:
Interventional
Actual Enrollment
:
33 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Other
Official Title:
An Open-Label, Single-center, Parallel, Phase 1 Study to Determine the Pharmacokinetics of Single- and Multiple- Oral Doses of TAK-438 10 mg and 20 mg in Healthy Adult Chinese Subjects
Actual Study Start Date
:
Apr 19, 2017
Actual Primary Completion Date
:
Aug 17, 2017
Actual Study Completion Date
:
Aug 17, 2017
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: TAK-438 10 milligram (mg) Once Daily TAK-438 10 mg, tablets, orally, once daily on Days 1, 3-9. Participants were required to fast for a minimum of 10 hours prior administration of assigned treatment. |
Drug: TAK-438
TAK-438 tablets.
|
| Experimental: TAK-438 20 mg Once Daily TAK-438 20 mg, tablets, orally, once daily on Days 1, 3-9. Participants were asked to fast for a minimum of 10 hours prior administration of assigned treatment. |
Drug: TAK-438
TAK-438 tablets.
|
| Experimental: TAK-438 20 mg Twice Daily TAK-438 20 mg, tablets, orally, once on Day 1 and twice daily on Days 3-9. Participants were asked to fast for a minimum of 10 hours prior to breakfast, followed by administration of assigned treatment 0.5 hours after breakfast and dinner. |
Drug: TAK-438
TAK-438 tablets.
|
Outcome Measures
Primary Outcome Measures
- Cmax: Maximum Observed Plasma Concentration for Free Base of TAK-438 (TAK-438F) and Its Metabolites M-I, M-II, M-III and M-IV-Sul on Day 1 [Day 1 pre-dose and at multiple timepoints (up to 48 hours) post-dose]
- Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-438F and Its Metabolites M-I, M-II, M-III and M-IV-Sul on Day 1 [Day 1 pre-dose and at multiple timepoints (up to 48 hours) post-dose]
- AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-438F and Its Metabolites M-I, M-II, M-III and M-IV-Sul on Day 1 [Day 1 pre-dose and at multiple timepoints (up to 48 hours) post-dose]
- AUCτ: Area Under the Plasma Concentration-time Curve From Time 0 to Tau Over the Dosing Interval for TAK-438F and Its Metabolites M-I, M-II, M-III and M-IV-Sul on Day 1 [Day 1 pre-dose and at multiple timepoints (up to 48 hours) post-dose]
- T1/2z: Terminal Disposition Half-life for TAK-438F and Its Metabolites M-I, M-II, M-III and M-IV-Sul on Day 1 [Day 1 pre-dose and at multiple timepoints (up to 48 hours) post-dose]
- Cmax,ss: Maximum Observed Plasma Concentration, at Steady State for TAK-438F and Its Metabolites M-I, M-II, M-III and M-IV-Sul on Day 9 [Day 9 pre-dose and at multiple timepoints (up to 24 hours for TAK-483 10 mg once daily and 20 mg once daily; up to 12 hours for TAK-438 20 mg twice daily) post-dose]
- Tmax, ss: Time to Reach the Maximum Plasma Concentration (Cmax) at Steady State for TAK-438F and Its Metabolites M-I, M-II, M-III and M-IV-Sul on Day 9 [Day 9 pre-dose and at multiple timepoints (up to 24 hours for TAK-483 10 mg once daily and 20 mg once daily; up to 12 hours for TAK-438 20 mg twice daily) post-dose]
- AUCτ,ss: Area Under the Plasma Concentration-time Curve During a Dosing Interval, at Steady State for TAK-438F and Its Metabolites M-I, M-II, M-III and M-IV-Sul on Day 9 [Day 9 pre-dose and at multiple timepoints (up to 24 hours for TAK-483 10 mg once daily and 20 mg once daily; up to 12 hours for TAK-438 20 mg twice daily) post-dose]
- Aet: Total Amount of Drug Excreted in Urine From Time 0 to Time T for TAK-438F and Its Metabolites M-I, M-II, M-III and M-IV-Sul on Day 1 [Day 1 pre-dose and at multiple timepoints (up to 48 hours) post-dose]
- Fe,t: Fraction of Drug Excreted in Urine From Time 0 to Time t for TAK-438F and Its Metabolites M-I, M-II, M-III and M-IV-Sul on Day 1 [Day 1 pre-dose and at multiple timepoints (up to 48 hours) post-dose]
- CLr: Renal Clearance for TAK-438F and Its Metabolites M-I, M-II, M-III and M-IV-Sul on Day 1 [Day 1 pre-dose and at multiple timepoints (up to 48 hours) post-dose]
- Aeτ: Amount of Drug Excreted in Urine During a Dosing Interval for TAK-438F and Its Metabolites M-I, M-II, M-III and M-IV-Sul on Day 9 [Day 9 pre-dose and at multiple timepoints (up to 24 hours for TAK-483 10 mg once daily and 20 mg once daily; up to 12 hours for TAK-438 20 mg twice daily) post-dose]
- Fe,τ: Fraction of Administered Dose of Drug Excreted in Urine During a Dosing Interval for TAK-438F and Its Metabolites M-I, M-II, M-III and M-IV-Sul on Day 9 [Day 9 pre-dose and at multiple timepoints (up to 24 hours for TAK-483 10 mg once daily and 20 mg once daily; up to 12 hours for TAK-438 20 mg twice daily) post-dose]
- CLR: Renal Clearance for TAK-438F and Its Metabolites M-I, M-II, M-III and M-IV-Sul on Day 9 [Day 9 pre-dose and at multiple timepoints (up to 24 hours for TAK-483 10 mg once daily and 20 mg once daily; up to 12 hours for TAK-438 20 mg twice daily) post-dose]
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
to 45 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
Yes
Inclusion Criteria:
-
Is a healthy adult male or female Chinese participant.
-
Is aged 18 to 45 years, inclusive, at the time of signing the informed consent form.
-
Weighs at least 50 kilogram (kg) and has a body mass index (BMI) between 19 and 26 kilogram per square meter (kg/m^2), inclusive at Screening (Check-In Day -1).
-
Is willing to abstain from caffeine and alcohol from 72 hours before first dose (Day
- until the Follow-up Visit on Day 18.
-
Is willing to abstain from strenuous exercise from 72 hours before first dose (Day 1) until the Follow-up Visit on Day 18.
-
Is willing to provide a sample for pharmacogenetic analysis (for cytochrome [CYP2C19] genotyping).
Exclusion Criteria:
-
Has uncontrolled, clinically significant cardiovascular disease or other abnormality, which may impact the ability of the participant to participate or potentially confound the study results.
-
Is lactose intolerant or has a known hypersensitivity to any component of the formulation of TAK-438.
-
Has poor peripheral venous access.
-
Has donated or lost 400 milliliter (mL) or more of his or her blood volume (including plasmapheresis), or had a transfusion of any blood product within 90 days prior to Day 1; or participant has donated or lost more than 200 mL or more of his or her blood in the last 28 days.
-
Has a history of symptomatic gastroesophageal reflux disease (GERD), Erosive Esophagitis, duodenal ulcer (DU), gastric ulcer (GU), dyspepsia, Barrett's Esophagus, or Zollinger-Ellison (ZE) syndrome or has current or recent (within 6 months) gastrointestinal disease that would be expected to influence the absorption of drugs.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Zhongshan Hospital Fudan University | Shanghai | China | 200032 |
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:
NCT03085836
Other Study ID Numbers:
- TAK-438_114
- U1111-1191-6949
- CTR20170137
First Posted:
Mar 21, 2017
Last Update Posted:
Jan 30, 2019
Last Verified:
Aug 1, 2018
Studies a U.S. FDA-regulated Drug Product:
No
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 1 investigative site in China from 19 April 2017 to 17 August 2017. |
|---|---|
| Pre-assignment Detail | Healthy Chinese participants were enrolled in this study to receive treatment in one of the 3 treatment groups: TAK-438 10 milligram (mg) once daily or TAK-438 20 mg once daily or TAK-438-20 mg twice daily. |
| Arm/Group Title | TAK-438 10 mg Once Daily | TAK-438 20 mg Once Daily | TAK-438 20 mg Twice Daily |
|---|---|---|---|
| Arm/Group Description | TAK-438 10 mg, tablet, orally, once daily on Days 1, 3 to 9. Participants were required to fast for a minimum of 10 hours prior administration of assigned treatment. | TAK-438 20 mg, tablet, orally, once daily on Days 1, 3 to 9. Participants were required to fast for a minimum of 10 hours prior administration of assigned treatment. | TAK-438 20 mg, tablet, orally, twice daily on Days 1, 3 to 9. Participants were required to fast for a minimum of 10 hours prior to breakfast, followed by administration of assigned treatment 0.5 hours after breakfast and dinner. |
| Period Title: Overall Study | |||
| STARTED | 12 | 11 | 10 |
| COMPLETED | 12 | 11 | 10 |
| NOT COMPLETED | 0 | 0 | 0 |
Baseline Characteristics
| Arm/Group Title | TAK-438 10 mg Once Daily | TAK-438 20 mg Once Daily | TAK-438 20 mg Twice Daily | Total |
|---|---|---|---|---|
| Arm/Group Description | TAK-438 10 mg, tablet, orally, once daily on Days 1, 3 to 9. Participants were required to fast for a minimum of 10 hours prior administration of assigned treatment. | TAK-438 20 mg, tablet, orally, once daily on Days 1, 3 to 9. Participants were required to fast for a minimum of 10 hours prior administration of assigned treatment. | TAK-438 20 mg, tablet, orally, twice daily on Days 1, 3 to 9. Participants were required to fast for a minimum of 10 hours prior to breakfast, followed by administration of assigned treatment 0.5 hours after breakfast and dinner. | Total of all reporting groups |
| Overall Participants | 12 | 11 | 10 | 33 |
| Age (years) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [years] |
25.2
(2.95)
|
23.9
(3.99)
|
27.2
(4.83)
|
25.4
(4.04)
|
| Sex: Female, Male (Count of Participants) | ||||
| Female |
6
50%
|
5
45.5%
|
4
40%
|
15
45.5%
|
| Male |
6
50%
|
6
54.5%
|
6
60%
|
18
54.5%
|
| Race (NIH/OMB) (Count of Participants) | ||||
| American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Asian |
12
100%
|
11
100%
|
10
100%
|
33
100%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Black or African American |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| White |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| More than one race |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Region of Enrollment (Count of Participants) | ||||
| China |
12
100%
|
11
100%
|
10
100%
|
33
100%
|
| Height (centimeter (cm)) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [centimeter (cm)] |
166.35
(8.426)
|
169.59
(7.672)
|
164.31
(9.377)
|
166.81
(8.498)
|
| Weight (kilogram (kg)) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [kilogram (kg)] |
62.63
(7.601)
|
66.05
(8.501)
|
61.66
(6.449)
|
63.47
(7.597)
|
| Body mass index (BMI) (kilogram per square meter (kg/m^2)) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [kilogram per square meter (kg/m^2)] |
22.63
(2.086)
|
22.89
(1.711)
|
22.88
(2.110)
|
22.79
(1.918)
|
| Smoking classification (Count of Participants) | ||||
| Never smoked |
12
100%
|
11
100%
|
10
100%
|
33
100%
|
| Alcohol consumption (Count of Participants) | ||||
| Never drank |
12
100%
|
11
100%
|
10
100%
|
33
100%
|
| Caffeine consumption (Count of Participants) | ||||
| Had no caffeine consumption |
12
100%
|
11
100%
|
10
100%
|
33
100%
|
| Cytochrome P450 2C19 (CYP2C19) Genotype (Count of Participants) | ||||
| *1/*1 |
5
41.7%
|
4
36.4%
|
4
40%
|
13
39.4%
|
| *1/*2 |
4
33.3%
|
6
54.5%
|
5
50%
|
15
45.5%
|
| *1/*3 |
1
8.3%
|
0
0%
|
0
0%
|
1
3%
|
| *2/*2 |
1
8.3%
|
1
9.1%
|
0
0%
|
2
6.1%
|
| *2/*3 |
1
8.3%
|
0
0%
|
1
10%
|
2
6.1%
|
| *3/*3 |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Outcome Measures
| Title | Cmax: Maximum Observed Plasma Concentration for Free Base of TAK-438 (TAK-438F) and Its Metabolites M-I, M-II, M-III and M-IV-Sul on Day 1 |
|---|---|
| Description | |
| Time Frame | Day 1 pre-dose and at multiple timepoints (up to 48 hours) post-dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| The PK set included all participants who received the study drug, had sufficient plasma/urine concentration data to calculate at least 1 PK parameter, and completed the minimum protocol specified procedures with no significant protocol deviations. |
| Arm/Group Title | TAK-438 10 mg Once Daily | TAK-438 20 mg Once Daily | TAK-438 20 mg Twice Daily |
|---|---|---|---|
| Arm/Group Description | TAK-438 10 mg, tablet, orally, once daily on Days 1, 3 to 9. Participants were required to fast for a minimum of 10 hours prior administration of assigned treatment. | TAK-438 20 mg, tablet, orally, once daily on Days 1, 3 to 9. Participants were required to fast for a minimum of 10 hours prior administration of assigned treatment. | TAK-438 20 mg, tablet, orally, twice daily on Days 1, 3 to 9. Participants were required to fast for a minimum of 10 hours prior to breakfast, followed by administration of assigned treatment 0.5 hours after breakfast and dinner. |
| Measure Participants | 12 | 11 | 10 |
| TAK-438F |
9.148
(2.9972)
|
18.18
(4.4973)
|
25.23
(10.017)
|
| M-I |
38.32
(8.6143)
|
67.95
(23.388)
|
59.02
(18.443)
|
| M-II |
2.840
(1.0442)
|
5.155
(2.7868)
|
4.879
(2.2426)
|
| M-III |
15.42
(3.7788)
|
25.63
(7.8650)
|
25.67
(5.9219)
|
| M-IV-Sul |
28.29
(5.0563)
|
60.67
(16.499)
|
42.28
(9.1174)
|
| Title | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-438F and Its Metabolites M-I, M-II, M-III and M-IV-Sul on Day 1 |
|---|---|
| Description | |
| Time Frame | Day 1 pre-dose and at multiple timepoints (up to 48 hours) post-dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| The PK set included all participants who received the study drug, had sufficient plasma/urine concentration data to calculate at least 1 PK parameter, and completed the minimum protocol specified procedures with no significant protocol deviations. |
| Arm/Group Title | TAK-438 10 mg Once Daily | TAK-438 20 mg Once Daily | TAK-438 20 mg Twice Daily |
|---|---|---|---|
| Arm/Group Description | TAK-438 10 mg, tablet, orally, once daily on Days 1, 3 to 9. Participants were required to fast for a minimum of 10 hours prior administration of assigned treatment. | TAK-438 20 mg, tablet, orally, once daily on Days 1, 3 to 9. Participants were required to fast for a minimum of 10 hours prior administration of assigned treatment. | TAK-438 20 mg, tablet, orally, twice daily on Days 1, 3 to 9. Participants were required to fast for a minimum of 10 hours prior to breakfast, followed by administration of assigned treatment 0.5 hours after breakfast and dinner. |
| Measure Participants | 12 | 11 | 10 |
| TAK-438F |
1.750
|
2.000
|
2.500
|
| M-I |
1.500
|
1.500
|
2.000
|
| M-II |
4.010
|
6.000
|
10.00
|
| M-III |
1.750
|
2.000
|
2.000
|
| M-IV-Sul |
1.500
|
1.500
|
2.000
|
| Title | AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-438F and Its Metabolites M-I, M-II, M-III and M-IV-Sul on Day 1 |
|---|---|
| Description | |
| Time Frame | Day 1 pre-dose and at multiple timepoints (up to 48 hours) post-dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| The PK set included all participants who received the study drug, had sufficient plasma/urine concentration data to calculate at least 1 PK parameter, and completed the minimum protocol specified procedures with no significant protocol deviations. |
| Arm/Group Title | TAK-438 10 mg Once Daily | TAK-438 20 mg Once Daily | TAK-438 20 mg Twice Daily |
|---|---|---|---|
| Arm/Group Description | TAK-438 10 mg, tablet, orally, once daily on Days 1, 3 to 9. Participants were required to fast for a minimum of 10 hours prior administration of assigned treatment. | TAK-438 20 mg, tablet, orally, once daily on Days 1, 3 to 9. Participants were required to fast for a minimum of 10 hours prior administration of assigned treatment. | TAK-438 20 mg, tablet, orally, twice daily on Days 1, 3 to 9. Participants were required to fast for a minimum of 10 hours prior to breakfast, followed by administration of assigned treatment 0.5 hours after breakfast and dinner. |
| Measure Participants | 12 | 11 | 10 |
| TAK-438F |
84.38
(29.197)
|
188.1
(43.066)
|
226.8
(67.128)
|
| M-I |
305.7
(88.227)
|
617.2
(213.56)
|
578.7
(144.15)
|
| M-II |
52.97
(22.843)
|
106.3
(74.306)
|
117.8
(41.170)
|
| M-III |
92.83
(34.769)
|
178.7
(64.779)
|
193.7
(56.808)
|
| M-IV-Sul |
132.5
(44.602)
|
307.5
(89.884)
|
240.8
(82.555)
|
| Title | AUCτ: Area Under the Plasma Concentration-time Curve From Time 0 to Tau Over the Dosing Interval for TAK-438F and Its Metabolites M-I, M-II, M-III and M-IV-Sul on Day 1 |
|---|---|
| Description | |
| Time Frame | Day 1 pre-dose and at multiple timepoints (up to 48 hours) post-dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| The PK set included all participants who received the study drug, had sufficient plasma/urine concentration data to calculate at least 1 PK parameter, and completed the minimum protocol specified procedures with no significant protocol deviations. |
| Arm/Group Title | TAK-438 10 mg Once Daily | TAK-438 20 mg Once Daily | TAK-438 20 mg Twice Daily |
|---|---|---|---|
| Arm/Group Description | TAK-438 10 mg, tablet, orally, once daily on Days 1, 3 to 9. Participants were required to fast for a minimum of 10 hours prior administration of assigned treatment. | TAK-438 20 mg, tablet, orally, once daily on Days 1, 3 to 9. Participants were required to fast for a minimum of 10 hours prior administration of assigned treatment. | TAK-438 20 mg, tablet, orally, twice daily on Days 1, 3 to 9. Participants were required to fast for a minimum of 10 hours prior to breakfast, followed by administration of assigned treatment 0.5 hours after breakfast and dinner. |
| Measure Participants | 12 | 11 | 10 |
| TAK-438F |
74.91
(24.835)
|
168.6
(37.455)
|
154.8
(38.920)
|
| M-I |
251.4
(77.758)
|
528.8
(182.62)
|
344.1
(91.089)
|
| M-II |
31.77
(18.646)
|
79.07
(56.206)
|
41.55
(19.189)
|
| M-III |
87.98
(31.136)
|
169.2
(59.474)
|
149.1
(36.714)
|
| M-IV-Sul |
127.1
(43.648)
|
296.0
(86.359)
|
192.8
(57.176)
|
| Title | T1/2z: Terminal Disposition Half-life for TAK-438F and Its Metabolites M-I, M-II, M-III and M-IV-Sul on Day 1 |
|---|---|
| Description | |
| Time Frame | Day 1 pre-dose and at multiple timepoints (up to 48 hours) post-dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| The PK set included all participants who received the study drug, had sufficient plasma/urine concentration data to calculate at least 1 PK parameter, and completed the minimum protocol specified procedures with no significant protocol deviations. PK analysis population where data at specified time points were available. |
| Arm/Group Title | TAK-438 10 mg Once Daily | TAK-438 20 mg Once Daily | TAK-438 20 mg Twice Daily |
|---|---|---|---|
| Arm/Group Description | TAK-438 10 mg, tablet, orally, once daily on Days 1, 3 to 9. Participants were required to fast for a minimum of 10 hours prior administration of assigned treatment. | TAK-438 20 mg, tablet, orally, once daily on Days 1, 3 to 9. Participants were required to fast for a minimum of 10 hours prior administration of assigned treatment. | TAK-438 20 mg, tablet, orally, twice daily on Days 1, 3 to 9. Participants were required to fast for a minimum of 10 hours prior to breakfast, followed by administration of assigned treatment 0.5 hours after breakfast and dinner. |
| Measure Participants | 12 | 11 | 10 |
| TAK-438F |
7.879
(1.2352)
|
6.996
(1.0110)
|
7.116
(0.71638)
|
| M-I |
10.82
(4.0923)
|
8.256
(1.2964)
|
8.385
(0.73316)
|
| M-II |
10.52
(4.3311)
|
10.37
(2.9973)
|
12.29
(4.0538)
|
| M-III |
6.695
(1.3786)
|
6.335
(1.1833)
|
6.791
(0.89228)
|
| M-IV-Sul |
4.753
(2.4430)
|
5.698
(1.2625)
|
5.521
(2.2225)
|
| Title | Cmax,ss: Maximum Observed Plasma Concentration, at Steady State for TAK-438F and Its Metabolites M-I, M-II, M-III and M-IV-Sul on Day 9 |
|---|---|
| Description | |
| Time Frame | Day 9 pre-dose and at multiple timepoints (up to 24 hours for TAK-483 10 mg once daily and 20 mg once daily; up to 12 hours for TAK-438 20 mg twice daily) post-dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| The PK set included all participants who received the study drug, had sufficient plasma/urine concentration data to calculate at least 1 PK parameter, and completed the minimum protocol specified procedures with no significant protocol deviations. |
| Arm/Group Title | TAK-438 10 mg Once Daily | TAK-438 20 mg Once Daily | TAK-438 20 mg Twice Daily |
|---|---|---|---|
| Arm/Group Description | TAK-438 10 mg, tablet, orally, once daily on Days 1, 3 to 9. Participants were required to fast for a minimum of 10 hours prior administration of assigned treatment. | TAK-438 20 mg, tablet, orally, once daily on Days 1, 3 to 9. Participants were required to fast for a minimum of 10 hours prior administration of assigned treatment. | TAK-438 20 mg, tablet, orally, twice daily on Days 1, 3 to 9. Participants were required to fast for a minimum of 10 hours prior to breakfast, followed by administration of assigned treatment 0.5 hours after breakfast and dinner. |
| Measure Participants | 12 | 11 | 10 |
| TAK-438F |
11.01
(3.4863)
|
23.43
(6.1433)
|
37.88
(10.910)
|
| M-I |
43.39
(9.6528)
|
79.85
(22.119)
|
59.55
(15.512)
|
| M-II |
3.558
(1.4983)
|
6.554
(2.6078)
|
9.174
(2.8376)
|
| M-III |
16.62
(4.1919)
|
30.15
(7.3228)
|
33.01
(6.1638)
|
| M-IV-Sul |
25.33
(3.6619)
|
54.08
(13.927)
|
39.74
(7.1405)
|
| Title | Tmax, ss: Time to Reach the Maximum Plasma Concentration (Cmax) at Steady State for TAK-438F and Its Metabolites M-I, M-II, M-III and M-IV-Sul on Day 9 |
|---|---|
| Description | |
| Time Frame | Day 9 pre-dose and at multiple timepoints (up to 24 hours for TAK-483 10 mg once daily and 20 mg once daily; up to 12 hours for TAK-438 20 mg twice daily) post-dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| The PK set included all participants who received the study drug, had sufficient plasma/urine concentration data to calculate at least 1 PK parameter, and completed the minimum protocol specified procedures with no significant protocol deviations. |
| Arm/Group Title | TAK-438 10 mg Once Daily | TAK-438 20 mg Once Daily | TAK-438 20 mg Twice Daily |
|---|---|---|---|
| Arm/Group Description | TAK-438 10 mg, tablet, orally, once daily on Days 1, 3 to 9. Participants were required to fast for a minimum of 10 hours prior administration of assigned treatment. | TAK-438 20 mg, tablet, orally, once daily on Days 1, 3 to 9. Participants were required to fast for a minimum of 10 hours prior administration of assigned treatment. | TAK-438 20 mg, tablet, orally, twice daily on Days 1, 3 to 9. Participants were required to fast for a minimum of 10 hours prior to breakfast, followed by administration of assigned treatment 0.5 hours after breakfast and dinner. |
| Measure Participants | 12 | 11 | 10 |
| TAK-438F |
1.500
|
2.000
|
3.000
|
| M-I |
1.500
|
1.000
|
2.500
|
| M-II |
4.000
|
3.000
|
3.500
|
| M-III |
1.750
|
2.000
|
3.000
|
| M-IV-Sul |
2.000
|
1.500
|
3.000
|
| Title | AUCτ,ss: Area Under the Plasma Concentration-time Curve During a Dosing Interval, at Steady State for TAK-438F and Its Metabolites M-I, M-II, M-III and M-IV-Sul on Day 9 |
|---|---|
| Description | |
| Time Frame | Day 9 pre-dose and at multiple timepoints (up to 24 hours for TAK-483 10 mg once daily and 20 mg once daily; up to 12 hours for TAK-438 20 mg twice daily) post-dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| The PK set included all participants who received the study drug, had sufficient plasma/urine concentration data to calculate at least 1 PK parameter, and completed the minimum protocol specified procedures with no significant protocol deviations. PK analysis population where data at specified time points were available. |
| Arm/Group Title | TAK-438 10 mg Once Daily | TAK-438 20 mg Once Daily | TAK-438 20 mg Twice Daily |
|---|---|---|---|
| Arm/Group Description | TAK-438 10 mg, tablet, orally, once daily on Days 1, 3 to 9. Participants were required to fast for a minimum of 10 hours prior administration of assigned treatment. | TAK-438 20 mg, tablet, orally, once daily on Days 1, 3 to 9. Participants were required to fast for a minimum of 10 hours prior administration of assigned treatment. | TAK-438 20 mg, tablet, orally, twice daily on Days 1, 3 to 9. Participants were required to fast for a minimum of 10 hours prior to breakfast, followed by administration of assigned treatment 0.5 hours after breakfast and dinner. |
| Measure Participants | 12 | 11 | 10 |
| TAK-438F |
93.90
(28.053)
|
212.7
(57.214)
|
273.4
(71.830)
|
| M-I |
285.5
(77.884)
|
581.1
(198.14)
|
435.3
(92.064)
|
| M-II |
46.31
(24.298)
|
105.5
(51.688)
|
100.4
(27.966)
|
| M-III |
95.94
(29.719)
|
194.6
(53.749)
|
222.6
(49.670)
|
| M-IV-Sul |
117.1
(37.489)
|
256.1
(62.786)
|
225.7
(52.675)
|
| Title | Aet: Total Amount of Drug Excreted in Urine From Time 0 to Time T for TAK-438F and Its Metabolites M-I, M-II, M-III and M-IV-Sul on Day 1 |
|---|---|
| Description | |
| Time Frame | Day 1 pre-dose and at multiple timepoints (up to 48 hours) post-dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| The PK set included all participants who received the study drug, had sufficient plasma/urine concentration data to calculate at least 1 PK parameter, and completed the minimum protocol specified procedures with no significant protocol deviations. |
| Arm/Group Title | TAK-438 10 mg Once Daily | TAK-438 20 mg Once Daily | TAK-438 20 mg Twice Daily |
|---|---|---|---|
| Arm/Group Description | TAK-438 10 mg, tablet, orally, once daily on Days 1, 3 to 9. Participants were required to fast for a minimum of 10 hours prior administration of assigned treatment. | TAK-438 20 mg, tablet, orally, once daily on Days 1, 3 to 9. Participants were required to fast for a minimum of 10 hours prior administration of assigned treatment. | TAK-438 20 mg, tablet, orally, twice daily on Days 1, 3 to 9. Participants were required to fast for a minimum of 10 hours prior to breakfast, followed by administration of assigned treatment 0.5 hours after breakfast and dinner. |
| Measure Participants | 12 | 11 | 10 |
| TAK-438F |
448.5
(159.06)
|
890.3
(243.24)
|
1478
(405.32)
|
| M-I |
176.6
(79.813)
|
253.1
(118.69)
|
211.2
(124.21)
|
| M-II |
0.000
(0.0000)
|
0.000
(0.0000)
|
0.000
(0.0000)
|
| M-III |
0.000
(0.0000)
|
0.000
(0.0000)
|
0.5120
(1.6191)
|
| M-IV-Sul |
205.4
(61.587)
|
422.1
(143.24)
|
387.1
(142.06)
|
| Title | Fe,t: Fraction of Drug Excreted in Urine From Time 0 to Time t for TAK-438F and Its Metabolites M-I, M-II, M-III and M-IV-Sul on Day 1 |
|---|---|
| Description | |
| Time Frame | Day 1 pre-dose and at multiple timepoints (up to 48 hours) post-dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| The PK set included all participants who received the study drug, had sufficient plasma/urine concentration data to calculate at least 1 PK parameter, and completed the minimum protocol specified procedures with no significant protocol deviations. |
| Arm/Group Title | TAK-438 10 mg Once Daily | TAK-438 20 mg Once Daily | TAK-438 20 mg Twice Daily |
|---|---|---|---|
| Arm/Group Description | TAK-438 10 mg, tablet, orally, once daily on Days 1, 3 to 9. Participants were required to fast for a minimum of 10 hours prior administration of assigned treatment. | TAK-438 20 mg, tablet, orally, once daily on Days 1, 3 to 9. Participants were required to fast for a minimum of 10 hours prior administration of assigned treatment. | TAK-438 20 mg, tablet, orally, twice daily on Days 1, 3 to 9. Participants were required to fast for a minimum of 10 hours prior to breakfast, followed by administration of assigned treatment 0.5 hours after breakfast and dinner. |
| Measure Participants | 12 | 11 | 10 |
| TAK-438F |
4.485
(1.5906)
|
4.448
(1.2093)
|
7.399
(2.0335)
|
| M-I |
1.760
(0.79678)
|
1.262
(0.59122)
|
1.053
(0.61992)
|
| M-II |
0.000
(0.0000)
|
0.000
(0.0000)
|
0.000
(0.0000)
|
| M-III |
0.000
(0.0000)
|
0.000
(0.0000)
|
0.002460
(0.0077792)
|
| M-IV-Sul |
1.609
(0.48258)
|
1.650
(0.56108)
|
1.513
(0.55536)
|
| Title | CLr: Renal Clearance for TAK-438F and Its Metabolites M-I, M-II, M-III and M-IV-Sul on Day 1 |
|---|---|
| Description | |
| Time Frame | Day 1 pre-dose and at multiple timepoints (up to 48 hours) post-dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| The PK set included all participants who received the study drug, had sufficient plasma/urine concentration data to calculate at least 1 PK parameter, and completed the minimum protocol specified procedures with no significant protocol deviations. PK analysis population where data at specified time points were available. |
| Arm/Group Title | TAK-438 10 mg Once Daily | TAK-438 20 mg Once Daily | TAK-438 20 mg Twice Daily |
|---|---|---|---|
| Arm/Group Description | TAK-438 10 mg, tablet, orally, once daily on Days 1, 3 to 9. Participants were required to fast for a minimum of 10 hours prior administration of assigned treatment. | TAK-438 20 mg, tablet, orally, once daily on Days 1, 3 to 9. Participants were required to fast for a minimum of 10 hours prior administration of assigned treatment. | TAK-438 20 mg, tablet, orally, twice daily on Days 1, 3 to 9. Participants were required to fast for a minimum of 10 hours prior to breakfast, followed by administration of assigned treatment 0.5 hours after breakfast and dinner. |
| Measure Participants | 12 | 11 | 10 |
| TAK-438F |
5.443
(1.0398)
|
4.922
(1.4362)
|
6.733
(1.3109)
|
| M-I |
0.6235
(0.16437)
|
0.4465
(0.24193)
|
0.3753
(0.19679)
|
| M-II |
0.000
(0.0000)
|
0.000
(0.0000)
|
0.000
(0.0000)
|
| M-III |
0.000
(0.0000)
|
0.000
(0.0000)
|
0.001820
(0.0057553)
|
| M-IV-Sul |
1.748
(0.65948)
|
1.527
(0.77444)
|
1.707
(0.47416)
|
| Title | Aeτ: Amount of Drug Excreted in Urine During a Dosing Interval for TAK-438F and Its Metabolites M-I, M-II, M-III and M-IV-Sul on Day 9 |
|---|---|
| Description | |
| Time Frame | Day 9 pre-dose and at multiple timepoints (up to 24 hours for TAK-483 10 mg once daily and 20 mg once daily; up to 12 hours for TAK-438 20 mg twice daily) post-dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| The PK set included all participants who received the study drug, had sufficient plasma/urine concentration data to calculate at least 1 PK parameter, and completed the minimum protocol specified procedures with no significant protocol deviations. |
| Arm/Group Title | TAK-438 10 mg Once Daily | TAK-438 20 mg Once Daily | TAK-438 20 mg Twice Daily |
|---|---|---|---|
| Arm/Group Description | TAK-438 10 mg, tablet, orally, once daily on Days 1, 3 to 9. Participants were required to fast for a minimum of 10 hours prior administration of assigned treatment. | TAK-438 20 mg, tablet, orally, once daily on Days 1, 3 to 9. Participants were required to fast for a minimum of 10 hours prior administration of assigned treatment. | TAK-438 20 mg, tablet, orally, twice daily on Days 1, 3 to 9. Participants were required to fast for a minimum of 10 hours prior to breakfast, followed by administration of assigned treatment 0.5 hours after breakfast and dinner. |
| Measure Participants | 12 | 11 | 10 |
| TAK-438F |
437.7
(121.93)
|
859.9
(155.66)
|
1327
(274.04)
|
| M-I |
224.3
(79.531)
|
354.1
(165.88)
|
340.9
(181.71)
|
| M-II |
0.000
(0.0000)
|
0.000
(0.0000)
|
0.000
(0.0000)
|
| M-III |
0.000
(0.0000)
|
0.000
(0.0000)
|
0.000
(0.0000)
|
| M-IV-Sul |
205.2
(52.172)
|
390.7
(99.477)
|
446.4
(139.39)
|
| Title | Fe,τ: Fraction of Administered Dose of Drug Excreted in Urine During a Dosing Interval for TAK-438F and Its Metabolites M-I, M-II, M-III and M-IV-Sul on Day 9 |
|---|---|
| Description | |
| Time Frame | Day 9 pre-dose and at multiple timepoints (up to 24 hours for TAK-483 10 mg once daily and 20 mg once daily; up to 12 hours for TAK-438 20 mg twice daily) post-dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| The PK set included all participants who received the study drug, had sufficient plasma/urine concentration data to calculate at least 1 PK parameter, and completed the minimum protocol specified procedures with no significant protocol deviations. |
| Arm/Group Title | TAK-438 10 mg Once Daily | TAK-438 20 mg Once Daily | TAK-438 20 mg Twice Daily |
|---|---|---|---|
| Arm/Group Description | TAK-438 10 mg, tablet, orally, once daily on Days 1, 3 to 9. Participants were required to fast for a minimum of 10 hours prior administration of assigned treatment. | TAK-438 20 mg, tablet, orally, once daily on Days 1, 3 to 9. Participants were required to fast for a minimum of 10 hours prior administration of assigned treatment. | TAK-438 20 mg, tablet, orally, twice daily on Days 1, 3 to 9. Participants were required to fast for a minimum of 10 hours prior to breakfast, followed by administration of assigned treatment 0.5 hours after breakfast and dinner. |
| Measure Participants | 12 | 11 | 10 |
| TAK-438F |
4.377
(1.2193)
|
4.299
(0.77678)
|
6.634
(1.3737)
|
| M-I |
2.236
(0.79323)
|
1.765
(0.82755)
|
1.700
(0.90664)
|
| M-II |
0.000
(0.0000)
|
0.000
(0.0000)
|
0.000
(0.0000)
|
| M-III |
0.000
(0.0000)
|
0.000
(0.0000)
|
0.000
(0.0000)
|
| M-IV-Sul |
1.605
(0.40853)
|
1.528
(0.38946)
|
1.748
(0.54499)
|
| Title | CLR: Renal Clearance for TAK-438F and Its Metabolites M-I, M-II, M-III and M-IV-Sul on Day 9 |
|---|---|
| Description | |
| Time Frame | Day 9 pre-dose and at multiple timepoints (up to 24 hours for TAK-483 10 mg once daily and 20 mg once daily; up to 12 hours for TAK-438 20 mg twice daily) post-dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| The PK set included all participants who received the study drug, had sufficient plasma/urine concentration data to calculate at least 1 PK parameter, and completed the minimum protocol specified procedures with no significant protocol deviations. PK analysis population where data at specified time points were available. |
| Arm/Group Title | TAK-438 10 mg Once Daily | TAK-438 20 mg Once Daily | TAK-438 20 mg Twice Daily |
|---|---|---|---|
| Arm/Group Description | TAK-438 10 mg, tablet, orally, once daily on Days 1, 3 to 9. Participants were required to fast for a minimum of 10 hours prior administration of assigned treatment. | TAK-438 20 mg, tablet, orally, once daily on Days 1, 3 to 9. Participants were required to fast for a minimum of 10 hours prior administration of assigned treatment. | TAK-438 20 mg, tablet, orally, twice daily on Days 1, 3 to 9. Participants were required to fast for a minimum of 10 hours prior to breakfast, followed by administration of assigned treatment 0.5 hours after breakfast and dinner. |
| Measure Participants | 12 | 11 | 10 |
| TAK-438F |
4.848
(1.2372)
|
4.251
(1.1565)
|
4.977
(0.71952)
|
| M-I |
0.8126
(0.26393)
|
0.6207
(0.22632)
|
0.7943
(0.39001)
|
| M-II |
0.000
(0.0000)
|
0.000
(0.0000)
|
0.000
(0.0000)
|
| M-III |
0.000
(0.0000)
|
0.000
(0.0000)
|
0.000
(0.0000)
|
| M-IV-Sul |
1.931
(0.79907)
|
1.614
(0.58643)
|
2.067
(0.70761)
|
Adverse Events
| Time Frame | Treatment-emergent adverse events are adverse events that started after the first dose of study drug up to follow-up (Day 1 up to Day 18) | |||||
|---|---|---|---|---|---|---|
| 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 | TAK-438 10 mg Once Daily | TAK-438 20 mg Once Daily | TAK-438 20 mg Twice Daily | |||
| Arm/Group Description | TAK-438 10 mg, tablet, orally, once daily on Days 1, 3 to 9. Participants were required to fast for a minimum of 10 hours prior administration of assigned treatment. | TAK-438 20 mg, tablet, orally, once daily on Days 1, 3 to 9. Participants were required to fast for a minimum of 10 hours prior administration of assigned treatment. | TAK-438 20 mg, tablet, orally, twice daily on Days 1, 3 to 9. Participants were required to fast for a minimum of 10 hours prior to breakfast, followed by administration of assigned treatment 0.5 hours after breakfast and dinner. | |||
All Cause Mortality |
||||||
| TAK-438 10 mg Once Daily | TAK-438 20 mg Once Daily | TAK-438 20 mg Twice Daily | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/12 (0%) | 0/11 (0%) | 0/10 (0%) | |||
Serious Adverse Events |
||||||
| TAK-438 10 mg Once Daily | TAK-438 20 mg Once Daily | TAK-438 20 mg Twice Daily | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/12 (0%) | 0/11 (0%) | 0/10 (0%) | |||
Other (Not Including Serious) Adverse Events |
||||||
| TAK-438 10 mg Once Daily | TAK-438 20 mg Once Daily | TAK-438 20 mg Twice Daily | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 4/12 (33.3%) | 6/11 (54.5%) | 4/10 (40%) | |||
| Cardiac disorders | ||||||
| Atrioventricular block first degree | 0/12 (0%) | 1/11 (9.1%) | 0/10 (0%) | |||
| Gastrointestinal disorders | ||||||
| Abdominal pain upper | 0/12 (0%) | 1/11 (9.1%) | 1/10 (10%) | |||
| Abdominal pain | 1/12 (8.3%) | 0/11 (0%) | 0/10 (0%) | |||
| Infections and infestations | ||||||
| Urinary tract infection | 0/12 (0%) | 1/11 (9.1%) | 0/10 (0%) | |||
| Investigations | ||||||
| White blood cells urine positive | 1/12 (8.3%) | 2/11 (18.2%) | 2/10 (20%) | |||
| Red blood cells urine positive | 2/12 (16.7%) | 0/11 (0%) | 2/10 (20%) | |||
| Neutrophil count increased | 1/12 (8.3%) | 1/11 (9.1%) | 0/10 (0%) | |||
| White blood cell count increased | 1/12 (8.3%) | 1/11 (9.1%) | 0/10 (0%) | |||
| Alanine aminotransferase increased | 0/12 (0%) | 0/11 (0%) | 1/10 (10%) | |||
| Aspartate aminotransferase increased | 0/12 (0%) | 0/11 (0%) | 1/10 (10%) | |||
| Blood creatine phosphokinase increased | 0/12 (0%) | 0/11 (0%) | 1/10 (10%) | |||
| Glucose urine present | 0/12 (0%) | 0/11 (0%) | 1/10 (10%) | |||
| Protein urine present | 0/12 (0%) | 0/11 (0%) | 1/10 (10%) | |||
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:
NCT03085836
Other Study ID Numbers:
- TAK-438_114
- U1111-1191-6949
- CTR20170137
First Posted:
Mar 21, 2017
Last Update Posted:
Jan 30, 2019
Last Verified:
Aug 1, 2018