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| ID | Type | Description | Link |
|---|---|---|---|
| U1111-1163-9637 | Registry Identifier | WHO |
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The purpose of this study is to evaluate the safety, tolerability, and pharmacokinetics of ascending single- and multiple-doses of TAK-020 in healthy participants.
The drug being tested in this study is called TAK-020. TAK-020 is being tested to evaluate safety and tolerability of single doses and 7 days multiple doses of TAK-020 in healthy volunteers. This study will look at the PK characteristics (how the drug acts throughout the body) of the drug and safety and tolerability (lab results, vital signs, ECG, and side effects) in healthy participants who take TAK-020.
The study will enroll a total of approximately 120 participants. This study is designed to consist of 2 sequential parts: Part 1-a SRD, and Part 2-a MRD. Healthy participants for Part 1 will be enrolled into 9 cohorts. Each cohort will have 8 randomized participants with receiving a single dose of TAK-020, and 2 receiving matching placebo under fasted conditions. In Cohorts 1-9 doses of 0.1, 0.5, 2.5, 4.4, 8.8, 17.5, 35, 70 and 105 mg will be evaluated.
Healthy participants for Part 2 will be enrolled into 7 cohorts. Each cohort will have 8 randomized participants, with participants receiving one dose of TAK-020 on Day 1, followed by a washout on Day 2, then daily dosing on Days 3-9 of TAK-020 with 2 participants receiving matching placebo under fasted conditions. In Cohorts 1-4 doses of 3.75, 5.75, 13 and 25 mg will be evaluated. For Cohorts 5-7, the subsequent dose level is to be determined based on data from Part 1 and review of safety, tolerability and PK data from Part 2 Cohorts 1-4.
This single-center trial will be conducted in the United States. The overall time to participate in this study is up to 45 days. Participants in Part 1 will make multiple visits to the clinic including a period of confinement to the clinic and will be contacted by telephone 14 days after the last dose of study drug for a follow-up assessment. Participants in Part 2 will make multiple visits to the clinic including a period of confinement to the clinic and will be observed at the clinic 17 days after the last dose of study drug for a follow-up assessment.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Part 1 Cohort 1-9: Placebo | Placebo Comparator | TAK-020 placebo-matching solution, orally, once on Day 1. |
|
| Part 1 Cohort 1: TAK-020 0.1 mg | Experimental | TAK-020 0.1 mg, solution, orally once on Day 1. |
|
| Part 1 Cohort 2: TAK-020 0.5 mg | Experimental | TAK-020 0.5 mg, solution, orally, once on Day 1 following review of safety, tolerability and pharmacokinetic (PK) data from Cohort 1. |
|
| Part 1 Cohort 3: TAK-020 2.5 mg | Experimental | TAK-020 2.5 mg, solution, orally once on Day 1 following review of safety, tolerability and PK data from Cohort 2. |
|
| Part 1 Cohort 4: TAK-020 4.4 mg | Experimental | TAK-020 4.4 mg, solution, orally once on Day 1 following review of safety, tolerability and PK data from Cohort 3. |
|
| Part 1 Cohort 5: TAK-020 8.8 mg |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| TAK-020 | Drug | TAK-020 oral solution |
|
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Participants Who Experience at Least One Treatment-emergent Adverse Event (TEAE) in Part 1 Single-rising Dose (SRD) | An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. A TEAE is defined as an adverse event that occurred or worsened after receiving study drug. | First dose of study drug up to and including 30 days after last dose of study drug (Up to 31 days) for Part 1 |
| Percentage of Participants With Markedly Abnormal Values (MAV) for Safety Laboratory Findings at Least Once Post-dose in Part 1 (SRD) | Safety laboratory tests includes hematology, serum chemistries, and urinalysis. | From Day 1 to Day 14 of Part 1 |
| Percentage of Participants With MAV for Vital Sign Measurements at Least Once Post-dose in Part 1 (SRD) | Vital signs include oral temperature, respiratory rate, sitting blood pressure (after 5 minutes resting) and pulse beats per minute (bpm). | From Day 1 to Day 14 of Part 1 |
| Percentage of Participants With MAV for Safety Electrocardiogram (ECG) Parameters at Least Once Post-dose in Part 1 (SRD) | A standard 12-lead ECG was performed. Change from baseline=CFB. | From Day 1 to Day 14 in Part 1 |
| Percentage of Participants Who Experience at Least One Treatment-emergent Adverse Event (TEAE) in Part 2 Multiple-rising Dose (MRD) | An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. A TEAE is defined as an adverse event that occurred or worsened after receiving study drug. |
| Measure | Description | Time Frame |
|---|---|---|
| Cmax: Maximum Observed Plasma Concentration for TAK-020 in Part 1 (SRD) | Pre-dose and multiple timepoints (up to 96 hours) post-dose in Part 1 | |
| Cmax: Maximum Observed Plasma Concentration for TAK-020 in Part 2 (MRD) | Pre-dose and multiple timepoints (up to 48 hours) post-dose on Day 1 and pre-dose and multiple timepoints (up to 24 hours) post-dose on Day 9 in Part 2 |
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Inclusion Criteria
Participant eligibility is determined according to the following criteria prior to entry into the study:
Exclusion Criteria
Any participant who meets any of the following criteria will not qualify for entry into the study:
The participant has received any investigational compound within 30 days prior to Screening.
The participant is an immediate family member, study site employee, or in a dependent relationship with a study site employee who is involved in the conduct of this study (example, spouse, parent, child, sibling) or may consent under duress.
Participant has a known hypersensitivity to any component of the formulation of TAK-020, Captisol or related compounds.
The participant has a positive urine drug result for drugs of abuse at Screening or Check-in (Day -1).
The participant has a history of drug abuse (defined as any illicit drug use) or a history of alcohol abuse (defined as 4 or more alcoholic beverages per day) within 1 year prior to the Screening visit or is unwilling to agree to abstain from alcohol and drugs throughout the study. One unit is equivalent to a half-pint of beer or 1 measure of spirits or 1 glass of wine.
Participant has taken any excluded medication, supplements, or food products, Prohibited Medications and Dietary Products.
If female, the participant is pregnant or lactating or intending to become pregnant before, during or within 1 month after exit from this study (30 days post last dose); or intending to donate ova during such time period.
If male, the participant intends to donate sperm during the course of this study or for 12 weeks thereafter.
Participant has evidence of current cardiovascular, central nervous system, hepatic, hematopoietic disease, renal dysfunction, metabolic or endocrine dysfunction, serious allergy, asthma hypoxemia, hypertension, seizures, or allergic skin rash. There is any finding in the participant's medical history, physical examination, or safety laboratory tests giving reasonable suspicion of a disease that would contraindicate taking TAK-020, or a similar drug in the same class, or that might interfere with the conduct of the study. This includes, but is not limited to, peptic ulcer disease, seizure disorders, and cardiac arrhythmias.
Participant has current or recent (within 6 months) gastrointestinal disease that would be expected to influence the absorption of drugs (that is, a history of malabsorption, esophageal reflux, peptic ulcer disease, erosive esophagitis frequent [more than once per week] occurrence of heartburn, or any surgical intervention [example, cholecystectomy]).
Participant has a history of cancer, except basal cell carcinoma which has been in remission for at least 5 years prior to Day 1.
Participant has used nicotine-containing products (including but not limited to cigarettes, pipes, cigars, chewing tobacco, nicotine patch or nicotine gum) within 28 days prior to Check-in Day -1. Cotinine test is positive at Screening or Check-in (Day -1).
The participant has poor peripheral venous access.
Participant has donated or lost 450 milliliter (mL) or more of his or her blood volume (including plasmapheresis), or had a transfusion of any blood product within 30 days prior to Day 1.
Vaccination with any live vaccine within 4 weeks of study drug administration.
Participant has a Screening or Check-in (Day -1) abnormal (clinically significant) ECG. Entry of any participant with an abnormal (not clinically significant) ECG must be approved, and documented by signature by the principal investigator medically qualified sub investigator.
Participant has QT interval with Fridericia correction method (QTcF) greater than (>) 450 millisecond (msec) for men and women or PR outside the range of 120 to 220 msec confirmed upon repeat testing within a maximum of 30 minutes, at the Screening Visit or Check-in (Day -1).
Participant has abnormal Screening or Day -1 laboratory values that suggest a clinically significant underlying disease or participant with the following lab abnormalities:
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| Name | Affiliation | Role |
|---|---|---|
| Medical Director Clinical Science | Takeda | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Glendale | California | United States |
Healthy volunteers were enrolled to receive TAK-020 oral solution Single Rising Doses (SRD) [0.1, 0.5, 2.5, 4.4, 8.8, 17.5, 35, 70, 105 milligrams (mgs)] or placebo in Part 1 or Multiple Rising Doses (MRD) [3.75, 5.75, 13, 25, 45, 60 mgs] or Placebo in Part 2.
Participants took part in the study at 1 investigative sites in the United States from 18 March 2015 to 04 May 2017.
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| ID | Title | Description |
|---|---|---|
| FG000 | Part 1 Cohort 1-9: Placebo | TAK-020 placebo-matching solution, orally, once on Day 1. |
| FG001 | Part 1 Cohort 1: TAK-020 0.1 mg | TAK-020 0.1 milligram (mg), solution, orally once on Day 1. |
| FG002 | Part 1 Cohort 2: TAK-020 0.5 mg | TAK-020 0.5 mg, solution, orally, once on Day 1 following review of safety, tolerability and pharmacokinetic (PK) data from Cohort 1. |
| FG003 | Part 1 Cohort 3: TAK-020 2.5 mg | TAK-020 2.5 mg, solution, orally once on Day 1 following review of safety, tolerability and PK data from Cohort 2. |
| FG004 | Part 1 Cohort 4: TAK-020 4.4 mg | TAK-020 4.4 mg, solution, orally once on Day 1 following review of safety, tolerability and PK data from Cohort 3. |
| FG005 | Part 1 Cohort 5: TAK-020 8.8 mg | TAK-020 8.8 mg, solution, orally once on Day 1 following review of safety, tolerability and PK data from Cohort 4. |
| FG006 | Part 1 Cohort 6: TAK-020 17.5 mg | TAK-020 17.5 mg, solution, orally once on Day 1 following review of safety, tolerability and PK data from Cohort 5. |
| FG007 | Part 1 Cohort 7: TAK-020 35 mg | TAK-020 35 mg, solution, orally once on Day 1. TAK-020 dose was determined based on review of safety, tolerability and PK data from Cohort 6. |
| FG008 | Part 1 Cohort 8: TAK-020 70 mg | TAK-020 70 mg, solution, orally once on Day 1. TAK-020 dose was determined based on review of safety, tolerability and PK data from Cohort 7. |
| FG009 | Part 1 Cohort 9: TAK-020 105 mg | TAK-020 105 mg, solution, orally once on Day 1. TAK-020 dose was determined based on review of safety, tolerability and PK data from Cohort 8. |
| FG010 | Part 2 Cohort 1-6: Placebo | TAK-020 placebo-matching solution, orally, once on Day 1 and Days 3 to 9. |
| FG011 | Part 2 Cohort 1: TAK-020 3.75 mg | TAK-020 3.75 mg, solution, orally once on Day 1 and Days 3-9. TAK-020 dose are determined based on data from Part 1 of the study. |
| FG012 | Part 2 Cohort 2: TAK-020 5.75 mg | TAK-020 5.75 mg, solution, orally once on Day 1 and Days 3-9. TAK-020 dose was determined based on data from Part 1 and review of safety, tolerability and PK data from Cohort 1 in Part 2. |
| FG013 | Part 2 Cohort 3: TAK-020 13 mg | TAK-020 13 mg, solution, orally once on Day 1 and Days 3-9. TAK-020 dose was determined based on data from Part 1 and review of safety, tolerability and PK data from Cohort 2 in Part 2. |
| FG014 | Part 2 Cohort 4: TAK-020 25 mg | TAK-020 25 mg, solution, orally once on Day 1 and Days 3-9. TAK-020 dose was determined based on data from Part 1 and review of safety, tolerability and PK data from Cohort 3 in Part 2. |
| FG015 | Part 2 Cohort 5: TAK-020 45 mg | TAK-020 45 mg, solution, orally once on Day 1 and Days 3-9. TAK-020 dose was determined based on data from Part 1 and review of safety, tolerability and PK data from Cohort 4 in Part 2. |
| FG016 | Part 2 Cohort 6: TAK-020 60 mg | TAK-020 60 mg, solution, orally once on Day 1 and Days 3-9. TAK-020 dose was determined based on data from Part 1 and review of safety, tolerability and PK data from Cohort 5 in Part 2. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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|
Safety Analysis Set was comprised of all participants who received study drug.
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| ID | Title | Description |
|---|---|---|
| BG000 | Part 1 Cohort 1-9: Placebo | TAK-020 placebo-matching solution, orally, once on Day 1. |
| BG001 | Part 1 Cohort 1: TAK-020 0.1 mg | TAK-020 0.1 milligram (mg), solution, orally once on Day 1. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| 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 | Percentage of Participants Who Experience at Least One Treatment-emergent Adverse Event (TEAE) in Part 1 Single-rising Dose (SRD) | An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. A TEAE is defined as an adverse event that occurred or worsened after receiving study drug. | Safety Analysis Set was comprised of all participants who received study drug. | Posted | Number | percentage of participants | First dose of study drug up to and including 30 days after last dose of study drug (Up to 31 days) for Part 1 |
|
First dose of study drug up to and including 30 days after last dose of study drug ( 31 Days for Part 1 and 39 days for Part 2)
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 | Part 1 Cohort 1-9: Placebo | TAK-020 placebo-matching solution, orally, once on Day 1. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Abdominal distension | Gastrointestinal disorders | MedDRA version: 19.0 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Medical Director | Takeda | +1-877-825-3327 | trialdisclosures@takeda.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Mar 27, 2017 | May 1, 2018 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | May 22, 2017 | May 1, 2018 | SAP_001.pdf |
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TAK-020 8.8 mg, solution, orally once on Day 1 following review of safety, tolerability and PK data from Cohort 4. |
|
| Part 1 Cohort 6: TAK-020 17.5 mg | Experimental | TAK-020 17.5 mg, solution, orally once on Day 1 following review of safety, tolerability and PK data from Cohort 5. |
|
| Part 1 Cohort 7: TAK-020 35 mg | Experimental | TAK-020 35 mg, solution, orally once on Day 1. TAK-020 dose will be determined based on review of safety, tolerability and PK data from Cohort 6. |
|
| Part 1 Cohort 8: TAK-020 70 mg | Experimental | TAK-020 70 mg, solution, orally once on Day 1. TAK-020 dose will be determined based on review of safety, tolerability and PK data from Cohort 7. |
|
| Part 1 Cohort 9: TAK-020 105 mg | Experimental | TAK-020 105 mg, solution, orally once on Day 1. TAK-020 dose will be determined based on review of safety, tolerability and PK data from Cohort 8. |
|
| Part 2 Cohort 1-6: Placebo | Placebo Comparator | TAK-020 placebo-matching solution, orally, once on Day 1 and Days 3 to 9. |
|
| Part 2 Cohort 1: TAK-020 3.75 mg | Experimental | TAK-020 3.75 mg, solution, orally once on Day 1 and Days 3-9. TAK-020 dose are determined based on data from Part 1 of the study. |
|
| Part 2 Cohort 2: TAK-020 5.75 mg | Experimental | TAK-020 5.75 mg, solution, orally once on Day 1 and Days 3-9. TAK-020 dose will be determined based on data from Part 1 and review of safety, tolerability and PK data from Cohort 1 in Part 2. |
|
| Part 2 Cohort 3: TAK-020 13 mg | Experimental | TAK-020 13 mg, solution, orally once on Day 1 and Days 3-9. TAK-020 dose will be determined based on data from Part 1 and review of safety, tolerability and PK data from Cohort 2 in Part 2. |
|
| Part 2 Cohort 4: TAK-020 25 mg | Experimental | TAK-020 25 mg, solution, orally once on Day 1 and Days 3-9. TAK-020 dose will be determined based on data from Part 1 and review of safety, tolerability and PK data from Cohort 3 in Part 2. |
|
| Part 2 Cohort 5: TAK-020 45 mg | Experimental | TAK-020 45 mg, solution, orally once on Day 1 and Days 3-9. TAK-020 dose was determined based on data from Part 1 and review of safety, tolerability and PK data from Cohort 4 in Part 2. |
|
| Part 2 Cohort 6: TAK-020 60 mg | Experimental | TAK-020 60 mg, solution, orally once on Day 1 and Days 3-9. TAK-020 dose was determined based on data from Part 1 and review of safety, tolerability and PK data from Cohort 5 in Part 2. |
|
| TAK-020 Placebo | Drug | TAK-020 placebo-matching oral solution |
|
| First dose of study drug up to and including 30 days after last dose of study drug (Up to 39 days) in Part 2 |
| Percentage of Participants With MAV for Safety Laboratory Findings at Least Once Post-dose in Part 2 (MRD) | Safety laboratory tests include hematology, and serum chemistries. | From Day 1 to Day 17 in Part 2 |
| Percentage of Participants With MAV for Vital Sign Measurements at Least Once Post-dose in Part 2 (MRD) | Vital signs include oral temperature respiratory rate, sitting blood pressure (after 5 minutes resting) and pulse (bpm). | From Day 1 to Day 17 in Part 2 |
| Percentage of Participants With MAV for Safety ECG Parameters at Least Once Post-dose in Part 2 (MRD) | A standard 12-lead ECG was performed. | From Day 1 to Day 17 in Part 2 |
| Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-020 in Part 1 (SRD) | Pre-dose and multiple timepoints (up to 96 hours) post-dose in Part 1 |
| Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-020 in Part 2 (MRD) | Pre-dose and multiple timepoints (up to 48 hours) post-dose on Day 1 and pre-dose and multiple time-points (up to 24 hours) post dose on Day 9 in Part 2 |
| AUC24: Area Under the Plasma Concentration-time Curve From Time 0 to Time 24 Hours for TAK-020 in Part 1 (SRD) | Pre-dose and multiple timepoints (up to 24 hours) post-dose in Part 1 |
| AUC24: Area Under the Plasma Concentration-time Curve From Time 0 to Time 24 Hours for TAK-020 in Part 2 (MRD) | Pre-dose and multiple timepoints (up to 24 hours) post-dose on Day 1 and pre-dose and multiple timepoints (up to 24 hours) post dose on Day 9 in Part 2 |
| AUC24/D: Area Under the Plasma Concentration-time Curve From Time 0 to Time 24 Hours Divided by TAK-020 Dose for TAK-020 in Part 1 (SRD) | Pre-dose and multiple timepoints (up to 24 hours) post-dose in Part 1 |
| AUC24/D: Area Under the Plasma Concentration-time Curve From Time 0 to Time 24 Hours Divided by TAK-020 Dose for TAK-020 in Part 2 (MRD) | Pre-dose and multiple timepoints (up to 24 Hours) post-dose on Day 1 and pre-dose and multiple timepoints (up to 24 hours) post-dose on Day 9 in Part 2 |
| AUCt: Area Under the Plasma Concentration-time Curve From Time 0 to Time t Over the Dosing Interval for TAK-020 (SRD) | Pre-dose and multiple timepoints (up to 96 hours) post-dose in Part 1 |
| AUCt: Area Under the Plasma Concentration-time Curve From Time 0 to Time t Over the Dosing Interval for TAK-020 in Part 2 (MRD) | Pre-dose and multiple timepoints (up to 48 hours) post-dose on Day 1 and pre-dose and multiple timepoints (up to 24 hours) post-dose on Day 9 in Part 2 |
| AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity Calculated Using the Observed Value for the Last Quantifiable Concentration for TAK-020 in Part 1 (SRD) | Pre-dose and multiple timepoints (up to 96 hours) post-dose in Part 1 |
| AUC∞:Area Under the Plasma Concentration-time Curve From Time 0 to Infinity Calculated Using the Observed Value for the Last Quantifiable Concentration for TAK-020 in Part 2 (MRD) | Pre-dose and multiple timepoints (up to 48 hours) post-dose on Day 1 in Part 2 |
| Rac(AUC): Accumulation Ratio Based on AUC Calculated as AUC24 at Steady State/AUC24 After a Single Dose for TAK-020 (MRD) | Pre-dose and multiple timepoints (up to 24 hours) post-dose on Day 9 in Part 2 |
| Rac(Cmax): Accumulation Ratio Based on Cmax Calculated as Cmax at Steady State/Cmax After a Single Dose for TAK-020 (MRD) | Pre-dose and multiple timepoints (up to 24 hours) post-dose on Day 9 in Part 2 |
| Cmax/D: Maximum Observed Plasma Concentration Divided by TAK-020 Dose for TAK-020 (SRD) | Pre-dose and multiple timepoints (up to 96 hours) post-dose in Part 1 |
| Cmax/D: Maximum Observed Plasma Concentration Divided by TAK-020 Dose for TAK-020 (MRD) | Pre-dose and multiple timepoints (up to 48 hours) post-dose on Day 1 and pre-dose and multiple timepoints (up to 24 hours) post-dose on Day 9 in Part 2 |
| Terminal Disposition Phase Half-life for TAK-020 in Part 1 (SRD) | Pre-dose and multiple timepoints (up to 96 hours) post-dose in Part 1 |
| T1/2z : Terminal Disposition Phase Half-life (T1/2z) for TAK-020 in Part 2 (MRD) | Pre-dose and multiple timepoints (up to 48 hours) post-dose on Day 1 and pre-dose and multiple timepoints (up to 24 hours) post-dose on Day 9 in Part 2 |
| Lambda z (Λz): Terminal Disposition Phase Rate Constant for TAK-020 (SRD) | Pre-dose and multiple timepoints (up to 96 hours) post-dose in Part 1 |
| Lamda z (Λz):Terminal Disposition Phase Rate Constant for TAK-020 (MRD) | From pre-dose to 96 hours post-dose in Part 1 and pre-dose and multiple timepoints (up to 24 hours) post-dose on Day 9 in Part 2 |
| Tlag: Lag Time to First Quantifiable Concentration for TAK-020 (SRD) | Pre-dose and multiple timepoints (up to 96 hours) post-dose in Part 1 |
| Tlag: Lag Time to First Quantifiable Concentration for TAK-020 (MRD) | Pre-dose and multiple timepoints (up to 48 hours) post-dose on Day 1 and pre-dose and multiple timepoints (up to 24 hours) post-dose on Day 9 in Part 2 |
| CL/F: Apparent Clearance After Extravascular Administration Calculated Using the Observed Value of the Last Quantifiable Concentration of TAK-020 in Part 1 (SRD) | CL/F was calculated as dose/AUC∞. | Pre-dose and multiple timepoints (up to 96 hours) post-dose in Part 1 |
| CL/F: Apparent Clearance After Extravascular Administration Calculated Using the Observed Value of the Last Quantifiable Concentration of TAK-020 in Part 2 (MRD) | CL/F was calculated as dose/AUCτ. | Pre-dose and multiple timepoints (up to 48 hours) post-dose on Day 1 and pre-dose and multiple timepoints (up to 24 hours) post-dose on Day 9 in Part 2 |
| Apparent Volume of Distribution (Vz/F) During the Terminal Disposition Phase After Extravascular Administration Calculated Using the Observed Value for the Last Quantifiable Concentration for TAK-020 in Part 1 (SRD) | Vz/F was calculated as (CL/F)/λz. | Pre-dose and multiple timepoints (up to 96 hours) post-dose in Part 1 |
| Apparent Volume of Distribution (Vz/F) During the Terminal Disposition Phase After Extravascular Administration Calculated Using the Observed Value for the Last Quantifiable Concentration for TAK-020 in Part 2 (MRD) | Vz/F was calculated as (CL/F)/λz. | Pre-dose and multiple timepoints (up to 48 hours) post-dose on Day 1 and pre-dose and multiple timepoints (up to 24 hours) post-dose on Day 9 in Part 2 |
| Ae(0-24) : Amount of Drug Excreted in Urine During a 24-hour Dosing Interval for TAK-020 in Part 1 (SRD) | Ae(0-24) was calculated as calculated as Cur*Vur, where Cur was the concentration of drug excreted in urine and Vur is the volume of urine excreted. | Pre-dose and multiple timepoints (up to 24 hours) post-dose in Part 1 |
| Ae(0-24): Amount of Drug Excreted in Urine During a 24-hour Dosing Interval for TAK-020 in Part 2 (MRD) | Ae(0-24) is calculated as calculated as Cur*Vur, where Cu was the concentration of drug excreted in urine and Vur is the volume of urine excreted. | Pre-dose and multiple timepoints (up to 24 hours) post-dose on Day 1 and Day 9 in Part 2 |
| Ae(0-96): Amount of Drug Excreted in Urine From Time 0 to Time 96 Hours for TAK-020 in Part 1 (SRD) | Pre-dose and multiple timepoints (up to 96 hours) post-dose in Part 1 |
| Fe(0-24): Fraction of Drug Excreted in Urine for TAK-020 in Part 1 (SRD) | Fe was calculated as (Aet/dose)*100. | Pre-dose and multiple timepoints (up to 24 hours) post-dose in Part 1 |
| Fe(0-24): Fraction of Drug Excreted in Urine for TAK-020 in Part 2 (MRD) | Fe was calculated as (Aet/dose)*100. | Pre-dose and multiple timepoints (up to 24 hours) post-dose on Day 1 and Day 9 in Part 2 |
| Fe(0-96): Fraction of Drug Excreted in Urine for TAK-020 in Part 1 (SRD) | Fe was calculated as (Aet/dose)*100. | Pre-dose and multiple timepoints (up to 96 hours) post-dose in Part 1 |
| Renal Clearance (CLr) for TAK-020 in Part 1 (SRD) | CLr was calculated as (Ae96/AUCt)*100. | Pre-dose and multiple timepoints (up to 96 hours) post-dose in Part 1 |
| Renal Clearance (CLr) for TAK-020 in Part 2 (MRD) | CLr was calculated as (Ae24/AUC24)*100. | Pre-dose and multiple timepoints (up to 48 hours) post-dose on Day 1 and pre-dose and multiple timepoints (up to 24 hours) post-dose on Day 9 in Part 2 |
| R: Linearity Index Calculated as AUC24 at Steady State/AUC∞ After a Single Dose for TAK-020 in Part 2 (MRD) | Pre-dose and multiple timepoints (Up to 48 hours) post-dose on Day 1 and pre-dose and multiple timepoints (up to 24 hours) post-dose on Day 9 in Part 2 |
| BG002 | Part 1 Cohort 2: TAK-020 0.5 mg | TAK-020 0.5 mg, solution, orally, once on Day 1 following review of safety, tolerability and pharmacokinetic (PK) data from Cohort 1. |
| BG003 | Part 1 Cohort 3: TAK-020 2.5 mg | TAK-020 2.5 mg, solution, orally once on Day 1 following review of safety, tolerability and PK data from Cohort 2. |
| BG004 | Part 1 Cohort 4: TAK-020 4.4 mg | TAK-020 4.4 mg, solution, orally once on Day 1 following review of safety, tolerability and PK data from Cohort 3. |
| BG005 | Part 1 Cohort 5: TAK-020 8.8 mg | TAK-020 8.8 mg, solution, orally once on Day 1 following review of safety, tolerability and PK data from Cohort 4. |
| BG006 | Part 1 Cohort 6: TAK-020 17.5 mg | TAK-020 17.5 mg, solution, orally once on Day 1 following review of safety, tolerability and PK data from Cohort 5. |
| BG007 | Part 1 Cohort 7: TAK-020 35 mg | TAK-020 35 mg, solution, orally once on Day 1. TAK-020 dose was determined based on review of safety, tolerability and PK data from Cohort 6. |
| BG008 | Part 1 Cohort 8: TAK-020 70 mg | TAK-020 70 mg, solution, orally once on Day 1. TAK-020 dose was determined based on review of safety, tolerability and PK data from Cohort 7. |
| BG009 | Part 1 Cohort 9: TAK-020 105 mg | TAK-020 105 mg, solution, orally once on Day 1. TAK-020 dose was determined based on review of safety, tolerability and PK data from Cohort 8. |
| BG010 | Part 2 Cohort 1-6: Placebo | TAK-020 placebo-matching solution, orally, once on Day 1 and Days 3 to 9. |
| BG011 | Part 2 Cohort 1: TAK-020 3.75 mg | TAK-020 3.75 mg, solution, orally once on Day 1 and Days 3-9. TAK-020 dose are determined based on data from Part 1 of the study. |
| BG012 | Part 2 Cohort 2: TAK-020 5.75 mg | TAK-020 5.75 mg, solution, orally once on Day 1 and Days 3-9. TAK-020 dose was determined based on data from Part 1 and review of safety, tolerability and PK data from Cohort 1 in Part 2. |
| BG013 | Part 2 Cohort 3: TAK-020 13 mg | TAK-020 13 mg, solution, orally once on Day 1 and Days 3-9. TAK-020 dose was determined based on data from Part 1 and review of safety, tolerability and PK data from Cohort 2 in Part 2. |
| BG014 | Part 2 Cohort 4: TAK-020 25 mg | TAK-020 25 mg, solution, orally once on Day 1 and Days 3-9. TAK-020 dose was determined based on data from Part 1 and review of safety, tolerability and PK data from Cohort 3 in Part 2. |
| BG015 | Part 2 Cohort 5: TAK-020 45 mg | TAK-020 45 mg, solution, orally once on Day 1 and Days 3-9. TAK-020 dose was determined based on data from Part 1 and review of safety, tolerability and PK data from Cohort 4 in Part 2. |
| BG016 | Part 2 Cohort 6: TAK-020 60 mg | TAK-020 60 mg, solution, orally once on Day 1 and Days 3-9. TAK-020 dose was determined based on data from Part 1 and review of safety, tolerability and PK data from Cohort 5 in Part 2. |
| BG017 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Count of Participants | Participants |
|
| Region of Enrollment | Count of Participants | Participants |
|
| Body Mass Index (BMI) | Body Mass Index = weight (kg)/[height (m)^2] | Mean | Standard Deviation | kg/m^2 |
|
| Smoking History | Count of Participants | Participants |
|
| Alcohol History | Count of Participants | Participants |
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| Alcohol Participant Consumed | Number of participants who consume alcohol <4 drinks/day is reported. | Assessment was performed on participants who were current drinkers. | Count of Participants | Participants |
|
| Caffeine Consumption | Count of Participants | Participants |
|
| Xanthine Consumption | Count of Participants | Participants |
|
| Female Reproductive Status | Count of Participants | Participants |
|
| Part 1 Cohort 1: TAK-020 0.1 mg |
TAK-020 0.1 milligram (mg), solution, orally once on Day 1. |
| OG002 | Part 1 Cohort 2: TAK-020 0.5 mg | TAK-020 0.5 mg, solution, orally, once on Day 1 following review of safety, tolerability and pharmacokinetic (PK) data from Cohort 1. |
| OG003 | Part 1 Cohort 3: TAK-020 2.5 mg | TAK-020 2.5 mg, solution, orally once on Day 1 following review of safety, tolerability and PK data from Cohort 2. |
| OG004 | Part 1 Cohort 4: TAK-020 4.4 mg | TAK-020 4.4 mg, solution, orally once on Day 1 following review of safety, tolerability and PK data from Cohort 3. |
| OG005 | Part 1 Cohort 5: TAK-020 8.8 mg | TAK-020 8.8 mg, solution, orally once on Day 1 following review of safety, tolerability and PK data from Cohort 4. |
| OG006 | Part 1 Cohort 6: TAK-020 17.5 mg | TAK-020 17.5 mg, solution, orally once on Day 1 following review of safety, tolerability and PK data from Cohort 5. |
| OG007 | Part 1 Cohort 7: TAK-020 35 mg | TAK-020 35 mg, solution, orally once on Day 1. TAK-020 dose was determined based on review of safety, tolerability and PK data from Cohort 6. |
| OG008 | Part 1 Cohort 8: TAK-020 70 mg | TAK-020 70 mg, solution, orally once on Day 1. TAK-020 dose was determined based on review of safety, tolerability and PK data from Cohort 7. |
| OG009 | Part 1 Cohort 9: TAK-020 105 mg | TAK-020 105 mg, solution, orally once on Day 1. TAK-020 dose was determined based on review of safety, tolerability and PK data from Cohort 8. |
|
|
| Primary | Percentage of Participants With Markedly Abnormal Values (MAV) for Safety Laboratory Findings at Least Once Post-dose in Part 1 (SRD) | Safety laboratory tests includes hematology, serum chemistries, and urinalysis. | Safety Analysis Set was comprised of all participants who received study drug. | Posted | Number | percentage of participants | From Day 1 to Day 14 of Part 1 |
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| Primary | Percentage of Participants With MAV for Vital Sign Measurements at Least Once Post-dose in Part 1 (SRD) | Vital signs include oral temperature, respiratory rate, sitting blood pressure (after 5 minutes resting) and pulse beats per minute (bpm). | Safety Analysis Set was comprised of all participants who received study drug. | Posted | Number | percentage of participants | From Day 1 to Day 14 of Part 1 |
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| Primary | Percentage of Participants With MAV for Safety Electrocardiogram (ECG) Parameters at Least Once Post-dose in Part 1 (SRD) | A standard 12-lead ECG was performed. Change from baseline=CFB. | Safety Analysis Set was comprised of all participants who received study drug. | Posted | Number | percentage of participants | From Day 1 to Day 14 in Part 1 |
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| Primary | Percentage of Participants Who Experience at Least One Treatment-emergent Adverse Event (TEAE) in Part 2 Multiple-rising Dose (MRD) | An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. A TEAE is defined as an adverse event that occurred or worsened after receiving study drug. | Safety Analysis Set was comprised of all participants who received study drug. | Posted | Number | percentage of participants | First dose of study drug up to and including 30 days after last dose of study drug (Up to 39 days) in Part 2 |
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| Primary | Percentage of Participants With MAV for Safety Laboratory Findings at Least Once Post-dose in Part 2 (MRD) | Safety laboratory tests include hematology, and serum chemistries. | Safety Analysis Set included all participants who received study drug. | Posted | Number | percentage of participants | From Day 1 to Day 17 in Part 2 |
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| Primary | Percentage of Participants With MAV for Vital Sign Measurements at Least Once Post-dose in Part 2 (MRD) | Vital signs include oral temperature respiratory rate, sitting blood pressure (after 5 minutes resting) and pulse (bpm). | Safety Analysis Set included all participants who received study drug. | Posted | Number | percentage of participants | From Day 1 to Day 17 in Part 2 |
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| Primary | Percentage of Participants With MAV for Safety ECG Parameters at Least Once Post-dose in Part 2 (MRD) | A standard 12-lead ECG was performed. | Safety Analysis Set included all participants who received study drug. | Posted | Number | percentage of participants | From Day 1 to Day 17 in Part 2 |
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| Secondary | Cmax: Maximum Observed Plasma Concentration for TAK-020 in Part 1 (SRD) | Pharmacokinetic set included all participants who received study drug and had at least one measurable plasma concentration or amount of drug in the urine. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | Pre-dose and multiple timepoints (up to 96 hours) post-dose in Part 1 |
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| Secondary | Cmax: Maximum Observed Plasma Concentration for TAK-020 in Part 2 (MRD) | Pharmacokinetic set included all participants who received study drug and had at least one measurable plasma concentration or amount of drug in the urine. Here, number analyzed are the participants who were evaluated for this outcome measure. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | Pre-dose and multiple timepoints (up to 48 hours) post-dose on Day 1 and pre-dose and multiple timepoints (up to 24 hours) post-dose on Day 9 in Part 2 |
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| Secondary | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-020 in Part 1 (SRD) | Pharmacokinetic set included all participants who received study drug and had at least one measurable plasma concentration or amount of drug in the urine. | Posted | Median | Full Range | hr | Pre-dose and multiple timepoints (up to 96 hours) post-dose in Part 1 |
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| Secondary | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-020 in Part 2 (MRD) | Pharmacokinetic set included all participants who received study drug and had at least one measurable plasma concentration or amount of drug in the urine. Here, number analyzed are the participants who were evaluated for this outcome measure. | Posted | Median | Full Range | hr | Pre-dose and multiple timepoints (up to 48 hours) post-dose on Day 1 and pre-dose and multiple time-points (up to 24 hours) post dose on Day 9 in Part 2 |
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| Secondary | AUC24: Area Under the Plasma Concentration-time Curve From Time 0 to Time 24 Hours for TAK-020 in Part 1 (SRD) | Pharmacokinetic set included all participants who received study drug and had at least one measurable plasma concentration or amount of drug in the urine. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng*hr/mL | Pre-dose and multiple timepoints (up to 24 hours) post-dose in Part 1 |
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| Secondary | AUC24: Area Under the Plasma Concentration-time Curve From Time 0 to Time 24 Hours for TAK-020 in Part 2 (MRD) | Pharmacokinetic set included all participants who received study drug and had at least one measurable plasma concentration or amount of drug in the urine. Here, number analyzed are the participants who were evaluated for this outcome measure. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng*hr/mL | Pre-dose and multiple timepoints (up to 24 hours) post-dose on Day 1 and pre-dose and multiple timepoints (up to 24 hours) post dose on Day 9 in Part 2 |
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| Secondary | AUC24/D: Area Under the Plasma Concentration-time Curve From Time 0 to Time 24 Hours Divided by TAK-020 Dose for TAK-020 in Part 1 (SRD) | Pharmacokinetic set included all participants who received study drug and had at least one measurable plasma concentration or amount of drug in the urine. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng*hr/mL/mg | Pre-dose and multiple timepoints (up to 24 hours) post-dose in Part 1 |
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| Secondary | AUC24/D: Area Under the Plasma Concentration-time Curve From Time 0 to Time 24 Hours Divided by TAK-020 Dose for TAK-020 in Part 2 (MRD) | Pharmacokinetic set included all participants who received study drug and had at least one measurable plasma concentration or amount of drug in the urine. Here, number analyzed are the participants who were evaluated for this outcome measure. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng*hr/mL/mg | Pre-dose and multiple timepoints (up to 24 Hours) post-dose on Day 1 and pre-dose and multiple timepoints (up to 24 hours) post-dose on Day 9 in Part 2 |
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| Secondary | AUCt: Area Under the Plasma Concentration-time Curve From Time 0 to Time t Over the Dosing Interval for TAK-020 (SRD) | Pharmacokinetic set included all participants who received study drug and had at least one measurable plasma concentration or amount of drug in the urine. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng*hr/mL | Pre-dose and multiple timepoints (up to 96 hours) post-dose in Part 1 |
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| Secondary | AUCt: Area Under the Plasma Concentration-time Curve From Time 0 to Time t Over the Dosing Interval for TAK-020 in Part 2 (MRD) | Pharmacokinetic set included all participants who received study drug and had at least one measurable plasma concentration or amount of drug in the urine. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng*hr/mL | Pre-dose and multiple timepoints (up to 48 hours) post-dose on Day 1 and pre-dose and multiple timepoints (up to 24 hours) post-dose on Day 9 in Part 2 |
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| Secondary | AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity Calculated Using the Observed Value for the Last Quantifiable Concentration for TAK-020 in Part 1 (SRD) | Pharmacokinetic set included all participants who received study drug and had at least one measurable plasma concentration or amount of drug in the urine. Here, number analyzed are the participants who were evaluated for this outcome measure. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng*hr/mL | Pre-dose and multiple timepoints (up to 96 hours) post-dose in Part 1 |
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| Secondary | AUC∞:Area Under the Plasma Concentration-time Curve From Time 0 to Infinity Calculated Using the Observed Value for the Last Quantifiable Concentration for TAK-020 in Part 2 (MRD) | Pharmacokinetic set included all participants who received study drug and had at least one measurable plasma concentration or amount of drug in the urine. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng*hr/mL | Pre-dose and multiple timepoints (up to 48 hours) post-dose on Day 1 in Part 2 |
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| Secondary | Rac(AUC): Accumulation Ratio Based on AUC Calculated as AUC24 at Steady State/AUC24 After a Single Dose for TAK-020 (MRD) | Pharmacokinetic set included all participants who received study drug and had at least one measurable plasma concentration or amount of drug in the urine. Here, number analyzed are the participants who were evaluated for this outcome measure. | Posted | Geometric Mean | Geometric Coefficient of Variation | ratio | Pre-dose and multiple timepoints (up to 24 hours) post-dose on Day 9 in Part 2 |
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| Secondary | Rac(Cmax): Accumulation Ratio Based on Cmax Calculated as Cmax at Steady State/Cmax After a Single Dose for TAK-020 (MRD) | Pharmacokinetic set included all participants who received study drug and had at least one measurable plasma concentration or amount of drug in the urine. Here, number analyzed are the participants who were evaluated for this outcome measure. | Posted | Geometric Mean | Geometric Coefficient of Variation | ratio | Pre-dose and multiple timepoints (up to 24 hours) post-dose on Day 9 in Part 2 |
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| Secondary | Cmax/D: Maximum Observed Plasma Concentration Divided by TAK-020 Dose for TAK-020 (SRD) | Pharmacokinetic set included all participants who received study drug and had at least one measurable plasma concentration or amount of drug in the urine. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL/mg | Pre-dose and multiple timepoints (up to 96 hours) post-dose in Part 1 |
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| Secondary | Cmax/D: Maximum Observed Plasma Concentration Divided by TAK-020 Dose for TAK-020 (MRD) | Pharmacokinetic set included all participants who received study drug and had at least one measurable plasma concentration or amount of drug in the urine. Here, number analyzed are the participants who were evaluated for this outcome measure. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL/mg | Pre-dose and multiple timepoints (up to 48 hours) post-dose on Day 1 and pre-dose and multiple timepoints (up to 24 hours) post-dose on Day 9 in Part 2 |
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| Secondary | Terminal Disposition Phase Half-life for TAK-020 in Part 1 (SRD) | Pharmacokinetic set included all participants who received study drug and had at least one measurable plasma concentration or amount of drug in the urine. Here, number analyzed are the participants who were evaluated for this outcome measure. | Posted | Mean | Standard Deviation | hr | Pre-dose and multiple timepoints (up to 96 hours) post-dose in Part 1 |
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| Secondary | T1/2z : Terminal Disposition Phase Half-life (T1/2z) for TAK-020 in Part 2 (MRD) | Pharmacokinetic set included all participants who received study drug and had at least one measurable plasma concentration or amount of drug in the urine. Here, number analyzed are the participants who were evaluated for this outcome measure. | Posted | Mean | Standard Deviation | hr | Pre-dose and multiple timepoints (up to 48 hours) post-dose on Day 1 and pre-dose and multiple timepoints (up to 24 hours) post-dose on Day 9 in Part 2 |
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| Secondary | Lambda z (Λz): Terminal Disposition Phase Rate Constant for TAK-020 (SRD) | Pharmacokinetic set included all participants who received study drug and had at least one measurable plasma concentration or amount of drug in the urine. | Posted | Mean | Standard Deviation | 1/hr | Pre-dose and multiple timepoints (up to 96 hours) post-dose in Part 1 |
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| Secondary | Lamda z (Λz):Terminal Disposition Phase Rate Constant for TAK-020 (MRD) | Pharmacokinetic set included all participants who received study drug and had at least one measurable plasma concentration or amount of drug in the urine. Here, number analyzed are the participants who were evaluated for this outcome measure. | Posted | Mean | Standard Deviation | 1/hr | From pre-dose to 96 hours post-dose in Part 1 and pre-dose and multiple timepoints (up to 24 hours) post-dose on Day 9 in Part 2 |
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| Secondary | Tlag: Lag Time to First Quantifiable Concentration for TAK-020 (SRD) | Pharmacokinetic set included all participants who received study drug and had at least one measurable plasma concentration or amount of drug in the urine. | Posted | Median | Full Range | hr | Pre-dose and multiple timepoints (up to 96 hours) post-dose in Part 1 |
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| Secondary | Tlag: Lag Time to First Quantifiable Concentration for TAK-020 (MRD) | Pharmacokinetic set included all participants who received study drug and had at least one measurable plasma concentration or amount of drug in the urine. Here, number analyzed are the participants who were evaluated for this outcome measure. | Posted | Median | Full Range | hr | Pre-dose and multiple timepoints (up to 48 hours) post-dose on Day 1 and pre-dose and multiple timepoints (up to 24 hours) post-dose on Day 9 in Part 2 |
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| Secondary | CL/F: Apparent Clearance After Extravascular Administration Calculated Using the Observed Value of the Last Quantifiable Concentration of TAK-020 in Part 1 (SRD) | CL/F was calculated as dose/AUC∞. | Pharmacokinetic set included all participants who received study drug and had at least one measurable plasma concentration or amount of drug in the urine. Here, number analyzed are the participants who were evaluated for this outcome measure. | Posted | Mean | Standard Deviation | L/h | Pre-dose and multiple timepoints (up to 96 hours) post-dose in Part 1 |
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| Secondary | CL/F: Apparent Clearance After Extravascular Administration Calculated Using the Observed Value of the Last Quantifiable Concentration of TAK-020 in Part 2 (MRD) | CL/F was calculated as dose/AUCτ. | Pharmacokinetic set included all participants who received study drug and had at least one measurable plasma concentration or amount of drug in the urine. Here, number analyzed are the participants who were evaluated for this outcome measure. | Posted | Mean | Standard Deviation | L/h | Pre-dose and multiple timepoints (up to 48 hours) post-dose on Day 1 and pre-dose and multiple timepoints (up to 24 hours) post-dose on Day 9 in Part 2 |
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| Secondary | Apparent Volume of Distribution (Vz/F) During the Terminal Disposition Phase After Extravascular Administration Calculated Using the Observed Value for the Last Quantifiable Concentration for TAK-020 in Part 1 (SRD) | Vz/F was calculated as (CL/F)/λz. | Pharmacokinetic set included all participants who received study drug and had at least one measurable plasma concentration or amount of drug in the urine. Here, number analyzed are the participants who were evaluated for this outcome measure. | Posted | Mean | Standard Deviation | L | Pre-dose and multiple timepoints (up to 96 hours) post-dose in Part 1 |
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| Secondary | Apparent Volume of Distribution (Vz/F) During the Terminal Disposition Phase After Extravascular Administration Calculated Using the Observed Value for the Last Quantifiable Concentration for TAK-020 in Part 2 (MRD) | Vz/F was calculated as (CL/F)/λz. | Pharmacokinetic set included all participants who received study drug and had at least one measurable plasma concentration or amount of drug in the urine. Here, number analyzed are the participants who were evaluated for this outcome measure. | Posted | Mean | Standard Deviation | L | Pre-dose and multiple timepoints (up to 48 hours) post-dose on Day 1 and pre-dose and multiple timepoints (up to 24 hours) post-dose on Day 9 in Part 2 |
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| Secondary | Ae(0-24) : Amount of Drug Excreted in Urine During a 24-hour Dosing Interval for TAK-020 in Part 1 (SRD) | Ae(0-24) was calculated as calculated as Cur*Vur, where Cur was the concentration of drug excreted in urine and Vur is the volume of urine excreted. | Pharmacokinetic set included all participants who received study drug and had at least one measurable plasma concentration or amount of drug in the urine. Here, number analyzed are the participants who were evaluated for this outcome measure. | Posted | Mean | Standard Deviation | mg | Pre-dose and multiple timepoints (up to 24 hours) post-dose in Part 1 |
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| Secondary | Ae(0-24): Amount of Drug Excreted in Urine During a 24-hour Dosing Interval for TAK-020 in Part 2 (MRD) | Ae(0-24) is calculated as calculated as Cur*Vur, where Cu was the concentration of drug excreted in urine and Vur is the volume of urine excreted. | Pharmacokinetic set included all participants who received study drug and had at least one measurable plasma concentration or amount of drug in the urine. Here, number analyzed are the participants who were evaluated for this outcome measure. | Posted | Mean | Standard Deviation | mg | Pre-dose and multiple timepoints (up to 24 hours) post-dose on Day 1 and Day 9 in Part 2 |
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| Secondary | Ae(0-96): Amount of Drug Excreted in Urine From Time 0 to Time 96 Hours for TAK-020 in Part 1 (SRD) | Pharmacokinetic set included all participants who received study drug and had at least one measurable plasma concentration or amount of drug in the urine. Here, number analyzed are the participants who were evaluated for this outcome measure. | Posted | Mean | Standard Deviation | mg | Pre-dose and multiple timepoints (up to 96 hours) post-dose in Part 1 |
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| Secondary | Fe(0-24): Fraction of Drug Excreted in Urine for TAK-020 in Part 1 (SRD) | Fe was calculated as (Aet/dose)*100. | Pharmacokinetic set included all participants who received study drug and had at least one measurable plasma concentration or amount of drug in the urine. Here, number analyzed are the participants who were evaluated for this outcome measure. | Posted | Mean | Standard Deviation | percentage of TAK-020 dose | Pre-dose and multiple timepoints (up to 24 hours) post-dose in Part 1 |
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| Secondary | Fe(0-24): Fraction of Drug Excreted in Urine for TAK-020 in Part 2 (MRD) | Fe was calculated as (Aet/dose)*100. | Pharmacokinetic set included all participants who received study drug and had at least one measurable plasma concentration or amount of drug in the urine. Here, number analyzed are the participants who were evaluated for this outcome measure. | Posted | Mean | Standard Deviation | percentage of TAK-020 dose | Pre-dose and multiple timepoints (up to 24 hours) post-dose on Day 1 and Day 9 in Part 2 |
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| Secondary | Fe(0-96): Fraction of Drug Excreted in Urine for TAK-020 in Part 1 (SRD) | Fe was calculated as (Aet/dose)*100. | Pharmacokinetic set included all participants who received study drug and had at least one measurable plasma concentration or amount of drug in the urine. Here, number analyzed are the participants who were evaluated for this outcome measure. | Posted | Mean | Standard Deviation | percentage of TAK-020 dose | Pre-dose and multiple timepoints (up to 96 hours) post-dose in Part 1 |
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| Secondary | Renal Clearance (CLr) for TAK-020 in Part 1 (SRD) | CLr was calculated as (Ae96/AUCt)*100. | Pharmacokinetic set included all participants who received study drug and had at least one measurable plasma concentration or amount of drug in the urine. Here, number analyzed are the participants who were evaluated for this outcome measure. | Posted | Mean | Standard Deviation | L/h | Pre-dose and multiple timepoints (up to 96 hours) post-dose in Part 1 |
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| Secondary | Renal Clearance (CLr) for TAK-020 in Part 2 (MRD) | CLr was calculated as (Ae24/AUC24)*100. | Pharmacokinetic set included all participants who received study drug and had at least one measurable plasma concentration or amount of drug in the urine. Here, number analyzed are the participants who were evaluated for this outcome measure. | Posted | Mean | Standard Deviation | L/h | Pre-dose and multiple timepoints (up to 48 hours) post-dose on Day 1 and pre-dose and multiple timepoints (up to 24 hours) post-dose on Day 9 in Part 2 |
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| Secondary | R: Linearity Index Calculated as AUC24 at Steady State/AUC∞ After a Single Dose for TAK-020 in Part 2 (MRD) | Pharmacokinetic set included all participants who received study drug and had at least one measurable plasma concentration or amount of drug in the urine. | Posted | Least Squares Mean | Standard Error | ratio | Pre-dose and multiple timepoints (Up to 48 hours) post-dose on Day 1 and pre-dose and multiple timepoints (up to 24 hours) post-dose on Day 9 in Part 2 |
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|
|
| 0 |
| 18 |
| 0 |
| 18 |
| 2 |
| 18 |
| EG001 | Part 1 Cohort 1: TAK-020 0.1 mg | TAK-020 0.1 milligram (mg), solution, orally once on Day 1. | 0 | 6 | 0 | 6 | 0 | 6 |
| EG002 | Part 1 Cohort 2: TAK-020 0.5 mg | TAK-020 0.5 mg, solution, orally, once on Day 1 following review of safety, tolerability and pharmacokinetic (PK) data from Cohort 1. | 0 | 6 | 0 | 6 | 0 | 6 |
| EG003 | Part 1 Cohort 3: TAK-020 2.5 mg | TAK-020 2.5 mg, solution, orally once on Day 1 following review of safety, tolerability and PK data from Cohort 2. | 0 | 6 | 0 | 6 | 1 | 6 |
| EG004 | Part 1 Cohort 4: TAK-020 4.4 mg | TAK-020 4.4 mg, solution, orally once on Day 1 following review of safety, tolerability and PK data from Cohort 3. | 0 | 6 | 0 | 6 | 0 | 6 |
| EG005 | Part 1 Cohort 5: TAK-020 8.8 mg | TAK-020 8.8 mg, solution, orally once on Day 1 following review of safety, tolerability and PK data from Cohort 4. | 0 | 6 | 0 | 6 | 1 | 6 |
| EG006 | Part 1 Cohort 6: TAK-020 17.5 mg | TAK-020 17.5 mg, solution, orally once on Day 1 following review of safety, tolerability and PK data from Cohort 5. | 0 | 6 | 0 | 6 | 0 | 6 |
| EG007 | Part 1 Cohort 7: TAK-020 35 mg | TAK-020 35 mg, solution, orally once on Day 1. TAK-020 dose was determined based on review of safety, tolerability and PK data from Cohort 6. | 0 | 6 | 0 | 6 | 0 | 6 |
| EG008 | Part 1 Cohort 8: TAK-020 70 mg | TAK-020 70 mg, solution, orally once on Day 1. TAK-020 dose was determined based on review of safety, tolerability and PK data from Cohort 7. | 0 | 6 | 0 | 6 | 3 | 6 |
| EG009 | Part 1 Cohort 9: TAK-020 105 mg | TAK-020 105 mg, solution, orally once on Day 1. TAK-020 dose was determined based on review of safety, tolerability and PK data from Cohort 8. | 0 | 6 | 0 | 6 | 1 | 6 |
| EG010 | Part 2 Cohort 1-6: Placebo | TAK-020 placebo-matching solution, orally, once on Day 1 and Days 3 to 9. | 0 | 12 | 0 | 12 | 5 | 12 |
| EG011 | Part 2 Cohort 1: TAK-020 3.75 mg | TAK-020 3.75 mg, solution, orally once on Day 1 and Days 3-9. TAK-020 dose are determined based on data from Part 1 of the study. | 0 | 6 | 0 | 6 | 1 | 6 |
| EG012 | Part 2 Cohort 2: TAK-020 5.75 mg | TAK-020 5.75 mg, solution, orally once on Day 1 and Days 3-9. TAK-020 dose was determined based on data from Part 1 and review of safety, tolerability and PK data from Cohort 1 in Part 2. | 0 | 6 | 0 | 6 | 3 | 6 |
| EG013 | Part 2 Cohort 3: TAK-020 13 mg | TAK-020 13 mg, solution, orally once on Day 1 and Days 3-9. TAK-020 dose was determined based on data from Part 1 and review of safety, tolerability and PK data from Cohort 2 in Part 2. | 0 | 6 | 0 | 6 | 3 | 6 |
| EG014 | Part 2 Cohort 4: TAK-020 25 mg | TAK-020 25 mg, solution, orally once on Day 1 and Days 3-9. TAK-020 dose was determined based on data from Part 1 and review of safety, tolerability and PK data from Cohort 3 in Part 2. | 0 | 6 | 0 | 6 | 2 | 6 |
| EG015 | Part 2 Cohort 5: TAK-020 45 mg | TAK-020 45 mg, solution, orally once on Day 1 and Days 3-9. TAK-020 dose was determined based on data from Part 1 and review of safety, tolerability and PK data from Cohort 4 in Part 2. | 0 | 6 | 0 | 6 | 1 | 6 |
| EG016 | Part 2 Cohort 6: TAK-020 60 mg | TAK-020 60 mg, solution, orally once on Day 1 and Days 3-9. TAK-020 dose was determined based on data from Part 1 and review of safety, tolerability and PK data from Cohort 5 in Part 2. | 0 | 6 | 0 | 6 | 1 | 6 |
| Abdominal pain upper | Gastrointestinal disorders | MedDRA version: 19.0 | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | MedDRA version: 19.0 | Systematic Assessment |
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| Decreased appetite | Metabolism and nutrition disorders | MedDRA version: 19.0 | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA version: 19.0 | Systematic Assessment |
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| Dizziness | Nervous system disorders | MedDRA version: 19.0 | Systematic Assessment |
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| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA version: 19.0 | Systematic Assessment |
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| Ecchymosis | Skin and subcutaneous tissue disorders | MedDRA version: 19.0 | Systematic Assessment |
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| Phlebitis | Vascular disorders | MedDRA version: 19.0 | Systematic Assessment |
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| Phlebitis superficial | Vascular disorders | MedDRA version: 19.0 | Systematic Assessment |
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| Diarrhoea | Gastrointestinal disorders | MedDRA version: 19.0 | Systematic Assessment |
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| Lip dry | Gastrointestinal disorders | MedDRA version: 19.0 | Systematic Assessment |
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| Axillary pain | General disorders | MedDRA version: 19.0 | Systematic Assessment |
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| Upper respiratory tract infection | Infections and infestations | MedDRA version: 19.0 | Systematic Assessment |
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| Musculoskeletal discomfort | Musculoskeletal and connective tissue disorders | MedDRA version: 19.0 | Systematic Assessment |
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| Hypoaesthesia | Nervous system disorders | MedDRA version: 19.0 | Systematic Assessment |
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| Somnolence | Nervous system disorders | MedDRA version: 19.0 | Systematic Assessment |
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| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA version: 19.0 | Systematic Assessment |
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| Nasal congestion | Respiratory, thoracic and mediastinal disorders | MedDRA version: 19.0 | Systematic Assessment |
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| Rhinorrhoea | Respiratory, thoracic and mediastinal disorders | MedDRA version: 19.0 | Systematic Assessment |
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| Sinus congestion | Respiratory, thoracic and mediastinal disorders | MedDRA version: 19.0 | Systematic Assessment |
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| Throat irritation | Respiratory, thoracic and mediastinal disorders | MedDRA version: 19.0 | Systematic Assessment |
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| Pruritus | Skin and subcutaneous tissue disorders | MedDRA version: 19.0 | Systematic Assessment |
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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.
| Male |
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| Sodium <130 mmol/L |
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| Sodium >150 mmol/L |
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| Bilirubin Total >34.2 umol/L |
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| Triglycerides >2.5*ULN |
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| Blood Urea Nitrogen (BUN) >10.7 mmol/L |
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| Pulse >120 bpm |
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| Systolic Blood Pressure <85 mm Hg |
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| Systolic Blood Pressure >180 mm Hg |
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| Diastolic Blood Pressure <50 mm Hg |
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| Diastolic Blood Pressure >110 mm Hg |
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| Body Temperature <35.6 C |
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| Body Temperature >37.7 C |
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| Heart Rate (beats/min) >120 |
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| PR Interval (msec[ms]) <=80 |
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| PR Interval (ms) >= 200 |
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| QT Interval (ms) <=300 |
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| QT Interval (ms) >=460 |
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| QTcB Interval (ms) <=300 |
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| QTcB Interval (ms) ≥500/ ≥30 CFB and ≥450 |
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| QTcF Interval (ms) <= 300 |
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| QTcF Interval (ms) ≥500/≥30 CFB and >= 450 |
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| QRS Interval (ms) <= 80 |
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| QRS Interval (ms) >= 180 |
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| Creatine Kinase >5*ULN (U/L) |
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| Lipase >3*ULN (U/L) |
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| Pulse >120 bpm |
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| Systolic Blood Pressure <85 mm Hg |
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| Systolic Blood Pressure >180 mm Hg |
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| Diastolic Blood Pressure <50 mm Hg |
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| Diastolic Blood Pressure >110 mm Hg |
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| Body Temperature <35.6 C |
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| Body Temperature >37.7 C |
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| Heart Rate (beats/min) >120 |
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| PR Interval (msec) <=80 |
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| PR Interval (msec) >=200 |
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| QT Interval (msec) <=300 |
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| QT Interval (msec) >=460 |
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| QTcB Interval (msec) <=300 |
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| QTcB Interval (ms) ≥500/≥ 30 CFB and ≥450 |
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| QTcF Interval (msec) <=300 |
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| QTcF Interval (ms) ≥500/≥30 CFB and >= 450 |
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| QRS Interval (msec) <=80 |
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| QRS Interval (msec) >=180 |
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| Day 9 |
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Day 9 |
| Power Model |
| 0.114 |
| Slope |
| 1.0900 |
| 2-Sided |
| 90 |
| 0.9962 |
| 1.1838 |
| Equivalence |
Dose proportionality is declared when the 90% confidence interval of the slope lies entirely within the critical region (0.9679, 1.0321) for the dose range of 0.1 mg to 105 mg. |
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| Day 9 |
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|
Day 9 |
| ANOVA |
Statistical analysis results were obtained using ANOVA with dose level as a fixed effect. |
| 0.4056 |
| Superiority |
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| Day 9 |
|
|
Day 9 |
| Power Model |
| 0.144 |
| Slope |
| 1.0929 |
| 2-Sided |
| 90 |
| 0.9878 |
| 1.1980 |
| Equivalence |
Dose proportionality is declared when the 90% confidence interval of the slope lies entirely within the critical region (0.9679, 1.0321) for the dose range of 0.1 mg to 105 mg. |
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| Day 9 |
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| Day 9 |
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| Day 9 |
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| Day 9 |
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| Day 9 |
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| Day 9 |
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| Day 9 |
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| Day 9 |
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| Day 9 |
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| Day 9 |
|
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| Day 9 |
|
| 1.156 |
| 2-Sided |
| 90 |
| 0.796 |
| 1.678 |
| Other |
| Estimated Ratio | 0.982 | 2-Sided | 90 | 0.676 | 1.425 | Other |
| Estimated Ratio | 1.055 | 2-Sided | 90 | 0.701 | 1.587 | Other |
| Estimated Ratio | 1.105 | 2-Sided | 90 | 0.761 | 1.604 | Other |
| Estimated Ratio | 1.225 | 2-Sided | 90 | 0.844 | 1.778 | Other |