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| ID | Type | Description | Link |
|---|---|---|---|
| U1111-1191-6949 | Registry Identifier | WHO | |
| CTR20170137 | Registry Identifier | CFDA |
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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.
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:
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| TAK-438 10 milligram (mg) Once Daily | Experimental | 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. |
|
| TAK-438 20 mg Once Daily | Experimental | 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. |
|
| TAK-438 20 mg Twice Daily | Experimental | 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| TAK-438 | Drug | TAK-438 tablets. |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Medical Director | Takeda | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Zhongshan Hospital Fudan University | Shanghai | 200032 | China |
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.
Participants took part in the study at 1 investigative site in China from 19 April 2017 to 17 August 2017.
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| ID | Title | Description |
|---|---|---|
| FG000 | TAK-438 10 mg Once Daily | 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. |
| FG001 | TAK-438 20 mg Once Daily | 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. |
| FG002 | TAK-438 20 mg Twice Daily | 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. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
The pharmacokinetic (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.
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| ID | Title | Description |
|---|---|---|
| BG000 | TAK-438 10 mg Once Daily | 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. |
| BG001 | TAK-438 20 mg Once Daily |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 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. |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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 | 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. | Posted | Mean | Standard Deviation | nanogram per milliliter (ng/mL) | Day 1 pre-dose and at multiple timepoints (up to 48 hours) post-dose |
|
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)
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.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | TAK-438 10 mg Once Daily | 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. |
Not provided
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Atrioventricular block first degree | Cardiac disorders | MedDRA (20.0) | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Medical Director | Takeda | +1-877-825-3327 | trialdisclosures@takeda.com |
Not provided
| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Dec 21, 2016 | Aug 15, 2018 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Aug 30, 2017 | Aug 15, 2018 | SAP_001.pdf |
Not provided
| ID | Term |
|---|---|
| C552956 | 1-(5-(2-fluorophenyl)-1-(pyridin-3-ylsulfonyl)-1H-pyrrol-3-yl)-N-methylmethanamine |
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| 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 |
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.
| BG002 | TAK-438 20 mg Twice Daily | 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. |
| BG003 | Total | Total of all reporting groups |
| Mean |
| Standard Deviation |
| years |
|
| Sex: Female, Male | 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. | Count of Participants | Participants |
|
| Race (NIH/OMB) | 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. | Count of Participants | Participants |
|
| Region of Enrollment | 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. | Count of Participants | Participants |
|
| Height | 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. | Mean | Standard Deviation | centimeter (cm) |
|
| Weight | 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. | Mean | Standard Deviation | kilogram (kg) |
|
| Body mass index (BMI) | 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. | Mean | Standard Deviation | kilogram per square meter (kg/m^2) |
|
| Smoking classification | 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. | Count of Participants | Participants |
|
| Alcohol consumption | 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. | Count of Participants | Participants |
|
| Caffeine consumption | 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. | Count of Participants | Participants |
|
| Cytochrome P450 2C19 (CYP2C19) Genotype | 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. | Count of Participants | Participants |
|
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. |
| OG002 | TAK-438 20 mg Twice Daily | 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. |
|
|
| Primary | 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 | 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. | Posted | Median | Full Range | hour | Day 1 pre-dose and at multiple timepoints (up to 48 hours) post-dose |
|
|
|
| Primary | 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 | 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. | Posted | Mean | Standard Deviation | hour*nanogram per milliliter (h*ng/mL) | Day 1 pre-dose and at multiple timepoints (up to 48 hours) post-dose |
|
|
|
| Primary | 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 | 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. | Posted | Mean | Standard Deviation | h*ng/mL | Day 1 pre-dose and at multiple timepoints (up to 48 hours) post-dose |
|
|
|
| Primary | 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 | 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. | Posted | Mean | Standard Deviation | hour | Day 1 pre-dose and at multiple timepoints (up to 48 hours) post-dose |
|
|
|
| Primary | 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 | 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. | Posted | Mean | Standard Deviation | ng/mL | 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 |
|
|
|
| Primary | 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 | 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. | Posted | Median | Full Range | hour | 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 |
|
|
|
| Primary | 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 | 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. | Posted | Mean | Standard Deviation | h*ng/mL | 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 |
|
|
|
| Primary | 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 | 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. | Posted | Mean | Standard Deviation | microgram (mcg) | Day 1 pre-dose and at multiple timepoints (up to 48 hours) post-dose |
|
|
|
| Primary | 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 | 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. | Posted | Mean | Standard Deviation | percentage of drug | Day 1 pre-dose and at multiple timepoints (up to 48 hours) post-dose |
|
|
|
| Primary | CLr: Renal Clearance for TAK-438F and Its Metabolites M-I, M-II, M-III and M-IV-Sul on Day 1 | 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. | Posted | Mean | Standard Deviation | liter per hour (L/h) | Day 1 pre-dose and at multiple timepoints (up to 48 hours) post-dose |
|
|
|
| Primary | 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 | 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. | Posted | Mean | Standard Deviation | mcg | 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 |
|
|
|
| Primary | 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 | 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. | Posted | Mean | Standard Deviation | percentage of drug | 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 |
|
|
|
| Primary | CLR: Renal Clearance for TAK-438F and Its Metabolites M-I, M-II, M-III and M-IV-Sul on Day 9 | 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. | Posted | Mean | Standard Deviation | L/h | 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 |
|
|
|
| 0 |
| 12 |
| 0 |
| 12 |
| 4 |
| 12 |
| EG001 | TAK-438 20 mg Once Daily | 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. | 0 | 11 | 0 | 11 | 6 | 11 |
| EG002 | TAK-438 20 mg Twice Daily | 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. | 0 | 10 | 0 | 10 | 4 | 10 |
| Abdominal pain upper | Gastrointestinal disorders | MedDRA (20.0) | Systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | MedDRA (20.0) | Systematic Assessment |
|
| Urinary tract infection | Infections and infestations | MedDRA (20.0) | Systematic Assessment |
|
| White blood cells urine positive | Investigations | MedDRA (20.0) | Systematic Assessment |
|
| Red blood cells urine positive | Investigations | MedDRA (20.0) | Systematic Assessment |
|
| Neutrophil count increased | Investigations | MedDRA (20.0) | Systematic Assessment |
|
| White blood cell count increased | Investigations | MedDRA (20.0) | Systematic Assessment |
|
| Alanine aminotransferase increased | Investigations | MedDRA (20.0) | Systematic Assessment |
|
| Aspartate aminotransferase increased | Investigations | MedDRA (20.0) | Systematic Assessment |
|
| Blood creatine phosphokinase increased | Investigations | MedDRA (20.0) | Systematic Assessment |
|
| Glucose urine present | Investigations | MedDRA (20.0) | Systematic Assessment |
|
| Protein urine present | Investigations | MedDRA (20.0) | Systematic Assessment |
|
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.
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