Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Ascending Single- and Multiple-Doses of TAK-020 in Healthy Volunteers

Sponsor
Takeda (Industry)
Overall Status
Completed
CT.gov ID
NCT02413255
Collaborator
(none)
120
1
17
25.6
4.7

Study Details

Study Description

Brief Summary

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.

Condition or Disease Intervention/Treatment Phase
Phase 1

Detailed Description

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.

Study Design

Study Type:
Interventional
Actual Enrollment :
120 participants
Allocation:
Randomized
Intervention Model:
Sequential Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
A Phase 1, Randomized, Double-Blind, Placebo-Controlled, Sequential-Panel, Ascending Single- and Multiple-Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of TAK-020 in Healthy Volunteers
Actual Study Start Date :
Mar 18, 2015
Actual Primary Completion Date :
May 4, 2017
Actual Study Completion Date :
May 4, 2017

Arms and Interventions

Arm Intervention/Treatment
Placebo Comparator: Part 1 Cohort 1-9: Placebo

TAK-020 placebo-matching solution, orally, once on Day 1.

Drug: TAK-020 Placebo
TAK-020 placebo-matching oral solution

Experimental: Part 1 Cohort 1: TAK-020 0.1 mg

TAK-020 0.1 mg, solution, orally once on Day 1.

Drug: TAK-020
TAK-020 oral solution

Experimental: 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.

Drug: TAK-020
TAK-020 oral solution

Experimental: 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.

Drug: TAK-020
TAK-020 oral solution

Experimental: 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.

Drug: TAK-020
TAK-020 oral solution

Experimental: 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.

Drug: TAK-020
TAK-020 oral solution

Experimental: 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.

Drug: TAK-020
TAK-020 oral solution

Experimental: Part 1 Cohort 7: TAK-020 35 mg

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.

Drug: TAK-020
TAK-020 oral solution

Experimental: Part 1 Cohort 8: TAK-020 70 mg

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.

Drug: TAK-020
TAK-020 oral solution

Experimental: Part 1 Cohort 9: TAK-020 105 mg

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.

Drug: TAK-020
TAK-020 oral solution

Placebo Comparator: Part 2 Cohort 1-6: Placebo

TAK-020 placebo-matching solution, orally, once on Day 1 and Days 3 to 9.

Drug: TAK-020 Placebo
TAK-020 placebo-matching oral solution

Experimental: 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.

Drug: TAK-020
TAK-020 oral solution

Experimental: 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 will be determined based on data from Part 1 and review of safety, tolerability and PK data from Cohort 1 in Part 2.

Drug: TAK-020
TAK-020 oral solution

Experimental: 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 will be determined based on data from Part 1 and review of safety, tolerability and PK data from Cohort 2 in Part 2.

Drug: TAK-020
TAK-020 oral solution

Experimental: 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 will be determined based on data from Part 1 and review of safety, tolerability and PK data from Cohort 3 in Part 2.

Drug: TAK-020
TAK-020 oral solution

Experimental: 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.

Drug: TAK-020
TAK-020 oral solution

Experimental: 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.

Drug: TAK-020
TAK-020 oral solution

Outcome Measures

Primary Outcome Measures

  1. Percentage of Participants Who Experience at Least One Treatment-emergent Adverse Event (TEAE) in Part 1 Single-rising Dose (SRD) [First dose of study drug up to and including 30 days after last dose of study drug (Up to 31 days) for Part 1]

    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.

  2. Percentage of Participants With Markedly Abnormal Values (MAV) for Safety Laboratory Findings at Least Once Post-dose in Part 1 (SRD) [From Day 1 to Day 14 of Part 1]

    Safety laboratory tests includes hematology, serum chemistries, and urinalysis.

  3. Percentage of Participants With MAV for Vital Sign Measurements at Least Once Post-dose in Part 1 (SRD) [From Day 1 to Day 14 of Part 1]

    Vital signs include oral temperature, respiratory rate, sitting blood pressure (after 5 minutes resting) and pulse beats per minute (bpm).

  4. Percentage of Participants With MAV for Safety Electrocardiogram (ECG) Parameters at Least Once Post-dose in Part 1 (SRD) [From Day 1 to Day 14 in Part 1]

    A standard 12-lead ECG was performed. Change from baseline=CFB.

  5. Percentage of Participants Who Experience at Least One Treatment-emergent Adverse Event (TEAE) in Part 2 Multiple-rising Dose (MRD) [First dose of study drug up to and including 30 days after last dose of study drug (Up to 39 days) in Part 2]

    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.

  6. Percentage of Participants With MAV for Safety Laboratory Findings at Least Once Post-dose in Part 2 (MRD) [From Day 1 to Day 17 in Part 2]

    Safety laboratory tests include hematology, and serum chemistries.

  7. Percentage of Participants With MAV for Vital Sign Measurements at Least Once Post-dose in Part 2 (MRD) [From Day 1 to Day 17 in Part 2]

    Vital signs include oral temperature respiratory rate, sitting blood pressure (after 5 minutes resting) and pulse (bpm).

  8. Percentage of Participants With MAV for Safety ECG Parameters at Least Once Post-dose in Part 2 (MRD) [From Day 1 to Day 17 in Part 2]

    A standard 12-lead ECG was performed.

Secondary Outcome Measures

  1. 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]

  2. 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]

  3. 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]

  4. 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]

  5. 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]

  6. 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]

  7. 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]

  8. 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]

  9. 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]

  10. 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]

  11. 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]

  12. 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]

  13. 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]

  14. 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]

  15. 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]

  16. 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]

  17. 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]

  18. 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]

  19. 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]

  20. 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]

  21. 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]

  22. 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]

  23. CL/F: Apparent Clearance After Extravascular Administration Calculated Using the Observed Value of the Last Quantifiable Concentration of TAK-020 in Part 1 (SRD) [Pre-dose and multiple timepoints (up to 96 hours) post-dose in Part 1]

    CL/F was calculated as dose/AUC∞.

  24. CL/F: Apparent Clearance After Extravascular Administration Calculated Using the Observed Value of the Last Quantifiable Concentration of 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]

    CL/F was calculated as dose/AUCτ.

  25. 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) [Pre-dose and multiple timepoints (up to 96 hours) post-dose in Part 1]

    Vz/F was calculated as (CL/F)/λz.

  26. 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) [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]

    Vz/F was calculated as (CL/F)/λz.

  27. Ae(0-24) : Amount of Drug Excreted in Urine During a 24-hour Dosing Interval for TAK-020 in Part 1 (SRD) [Pre-dose and multiple timepoints (up to 24 hours) post-dose in Part 1]

    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.

  28. Ae(0-24): Amount of Drug Excreted in Urine During a 24-hour Dosing Interval for TAK-020 in Part 2 (MRD) [Pre-dose and multiple timepoints (up to 24 hours) post-dose on Day 1 and Day 9 in Part 2]

    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.

  29. 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]

  30. Fe(0-24): Fraction of Drug Excreted in Urine for TAK-020 in Part 1 (SRD) [Pre-dose and multiple timepoints (up to 24 hours) post-dose in Part 1]

    Fe was calculated as (Aet/dose)*100.

  31. Fe(0-24): Fraction of Drug Excreted in Urine for TAK-020 in Part 2 (MRD) [Pre-dose and multiple timepoints (up to 24 hours) post-dose on Day 1 and Day 9 in Part 2]

    Fe was calculated as (Aet/dose)*100.

  32. Fe(0-96): Fraction of Drug Excreted in Urine for TAK-020 in Part 1 (SRD) [Pre-dose and multiple timepoints (up to 96 hours) post-dose in Part 1]

    Fe was calculated as (Aet/dose)*100.

  33. Renal Clearance (CLr) for TAK-020 in Part 1 (SRD) [Pre-dose and multiple timepoints (up to 96 hours) post-dose in Part 1]

    CLr was calculated as (Ae96/AUCt)*100.

  34. Renal Clearance (CLr) 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]

    CLr was calculated as (Ae24/AUC24)*100.

  35. 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]

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years to 55 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
Yes

Inclusion Criteria

Participant eligibility is determined according to the following criteria prior to entry into the study:

  1. In the opinion of the investigator, the participant is capable of understanding and complying with protocol requirements.

  2. Participant or, when applicable, the participant's legally acceptable representative signs and dates a written, informed consent form and any required privacy authorization prior to the initiation of any study procedures including requesting that a participant fast for any laboratory evaluations.

  3. Participant is a healthy adult male or female.

  4. The participant is a health adult male or female aged 18 to 55 years, inclusive, at the time of informed consent and first study medication dose.

  5. The participant weighs at least 45 kilogram (kg) and has a body mass index (BMI) between 18.0 and 32.0 kilogram per square meter (kg/m^2), inclusive at Screening and Day -1.

  6. A male participant who is nonsterilized and sexually active with a female partner of childbearing potential agrees to use adequate contraception from signing of informed consent throughout the duration of the study and for 12 weeks after last dose.

  7. A female participant of childbearing potential who is sexually active with a nonsterilized male partner agrees to use adequate contraception from signing of informed consent throughout the duration of the study and until the next menstrual period or 30 days after last dose, whichever is first. If the next menstrual period is delayed, a pregnancy test will be required for exclusion of pregnancy.

Exclusion Criteria

Any participant who meets any of the following criteria will not qualify for entry into the study:

  1. The participant has received any investigational compound within 30 days prior to Screening.

  2. 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.

  3. Participant has a known hypersensitivity to any component of the formulation of TAK-020, Captisol or related compounds.

  4. The participant has a positive urine drug result for drugs of abuse at Screening or Check-in (Day -1).

  5. 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.

  6. Participant has taken any excluded medication, supplements, or food products, Prohibited Medications and Dietary Products.

  7. 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.

  8. If male, the participant intends to donate sperm during the course of this study or for 12 weeks thereafter.

  9. 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.

  10. 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]).

  11. Participant has a history of cancer, except basal cell carcinoma which has been in remission for at least 5 years prior to Day 1.

  12. 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).

  13. The participant has poor peripheral venous access.

  14. 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.

  15. Vaccination with any live vaccine within 4 weeks of study drug administration.

  16. 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.

  17. 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).

  18. Participant has abnormal Screening or Day -1 laboratory values that suggest a clinically significant underlying disease or participant with the following lab abnormalities:

  19. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >1.2* the upper limit of normal (ULN).

  20. Positive screen test for drugs of abuse.

  21. Positive blood screen for hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV), or human immunodeficiency virus-1 or -2 antibodies.

  22. A positive test for tuberculosis (TB) (QuantiFERON).

Contacts and Locations

Locations

Site City State Country Postal Code
1 Glendale California United States

Sponsors and Collaborators

  • Takeda

Investigators

  • Study Director: Medical Director Clinical Science, Takeda

Study Documents (Full-Text)

More Information

Publications

None provided.
Responsible Party:
Takeda
ClinicalTrials.gov Identifier:
NCT02413255
Other Study ID Numbers:
  • TAK-020-1001
  • U1111-1163-9637
First Posted:
Apr 9, 2015
Last Update Posted:
Jan 7, 2019
Last Verified:
Jun 1, 2018
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by Takeda

Study Results

Participant Flow

Recruitment Details Participants took part in the study at 1 investigative sites in the United States from 18 March 2015 to 04 May 2017.
Pre-assignment Detail 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.
Arm/Group Title Part 1 Cohort 1-9: Placebo Part 1 Cohort 1: TAK-020 0.1 mg Part 1 Cohort 2: TAK-020 0.5 mg Part 1 Cohort 3: TAK-020 2.5 mg Part 1 Cohort 4: TAK-020 4.4 mg Part 1 Cohort 5: TAK-020 8.8 mg Part 1 Cohort 6: TAK-020 17.5 mg Part 1 Cohort 7: TAK-020 35 mg Part 1 Cohort 8: TAK-020 70 mg Part 1 Cohort 9: TAK-020 105 mg Part 2 Cohort 1-6: Placebo Part 2 Cohort 1: TAK-020 3.75 mg Part 2 Cohort 2: TAK-020 5.75 mg Part 2 Cohort 3: TAK-020 13 mg Part 2 Cohort 4: TAK-020 25 mg Part 2 Cohort 5: TAK-020 45 mg Part 2 Cohort 6: TAK-020 60 mg
Arm/Group Description TAK-020 placebo-matching solution, orally, once on Day 1. TAK-020 0.1 milligram (mg), solution, orally once on Day 1. TAK-020 0.5 mg, solution, orally, once on Day 1 following review of safety, tolerability and pharmacokinetic (PK) data from Cohort 1. TAK-020 2.5 mg, solution, orally once on Day 1 following review of safety, tolerability and PK data from Cohort 2. TAK-020 4.4 mg, solution, orally once on Day 1 following review of safety, tolerability and PK data from Cohort 3. TAK-020 8.8 mg, solution, orally once on Day 1 following review of safety, tolerability and PK data from Cohort 4. TAK-020 17.5 mg, solution, orally once on Day 1 following review of safety, tolerability and PK data from Cohort 5. 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. 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. 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. TAK-020 placebo-matching solution, orally, once on Day 1 and Days 3 to 9. 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. 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. 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. 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. 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. 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.
Period Title: Overall Study
STARTED 18 6 6 6 6 6 6 6 6 6 12 6 6 6 6 6 6
COMPLETED 18 6 6 6 6 6 6 6 6 6 12 6 6 6 5 6 6
NOT COMPLETED 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1 0 0

Baseline Characteristics

Arm/Group Title Part 1 Cohort 1-9: Placebo Part 1 Cohort 1: TAK-020 0.1 mg Part 1 Cohort 2: TAK-020 0.5 mg Part 1 Cohort 3: TAK-020 2.5 mg Part 1 Cohort 4: TAK-020 4.4 mg Part 1 Cohort 5: TAK-020 8.8 mg Part 1 Cohort 6: TAK-020 17.5 mg Part 1 Cohort 7: TAK-020 35 mg Part 1 Cohort 8: TAK-020 70 mg Part 1 Cohort 9: TAK-020 105 mg Part 2 Cohort 1-6: Placebo Part 2 Cohort 1: TAK-020 3.75 mg Part 2 Cohort 2: TAK-020 5.75 mg Part 2 Cohort 3: TAK-020 13 mg Part 2 Cohort 4: TAK-020 25 mg Part 2 Cohort 5: TAK-020 45 mg Part 2 Cohort 6: TAK-020 60 mg Total
Arm/Group Description TAK-020 placebo-matching solution, orally, once on Day 1. TAK-020 0.1 milligram (mg), solution, orally once on Day 1. TAK-020 0.5 mg, solution, orally, once on Day 1 following review of safety, tolerability and pharmacokinetic (PK) data from Cohort 1. TAK-020 2.5 mg, solution, orally once on Day 1 following review of safety, tolerability and PK data from Cohort 2. TAK-020 4.4 mg, solution, orally once on Day 1 following review of safety, tolerability and PK data from Cohort 3. TAK-020 8.8 mg, solution, orally once on Day 1 following review of safety, tolerability and PK data from Cohort 4. TAK-020 17.5 mg, solution, orally once on Day 1 following review of safety, tolerability and PK data from Cohort 5. 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. 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. 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. TAK-020 placebo-matching solution, orally, once on Day 1 and Days 3 to 9. 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. 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. 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. 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. 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. 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. Total of all reporting groups
Overall Participants 18 6 6 6 6 6 6 6 6 6 12 6 6 6 6 6 6 120
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]
35.1
(10.93)
46.0
(10.06)
38.0
(11.15)
38.0
(11.82)
29.0
(11.82)
35.8
(11.44)
38.2
(12.56)
33.7
(8.24)
34.3
(12.61)
34.8
(7.81)
37.0
(8.83)
34.2
(8.59)
43.2
(9.02)
29.3
(9.40)
35.7
(9.40)
36.2
(11.96)
34.8
(10.01)
36.0
(10.38)
Sex: Female, Male (Count of Participants)
Female
11
61.1%
2
33.3%
0
0%
3
50%
5
83.3%
3
50%
3
50%
1
16.7%
2
33.3%
0
0%
5
41.7%
0
0%
3
50%
0
0%
1
16.7%
1
16.7%
0
0%
40
33.3%
Male
7
38.9%
4
66.7%
6
100%
3
50%
1
16.7%
3
50%
3
50%
5
83.3%
4
66.7%
6
100%
7
58.3%
6
100%
3
50%
6
100%
5
83.3%
5
83.3%
6
100%
80
66.7%
Race/Ethnicity, Customized (Count of Participants)
Hispanic or Latino
2
11.1%
0
0%
0
0%
0
0%
3
50%
1
16.7%
1
16.7%
1
16.7%
2
33.3%
2
33.3%
2
16.7%
1
16.7%
4
66.7%
3
50%
1
16.7%
2
33.3%
0
0%
25
20.8%
Non-Hispanic and Latino
16
88.9%
6
100%
6
100%
6
100%
3
50%
5
83.3%
5
83.3%
5
83.3%
4
66.7%
4
66.7%
10
83.3%
5
83.3%
2
33.3%
3
50%
5
83.3%
4
66.7%
6
100%
95
79.2%
Race/Ethnicity, Customized (Count of Participants)
Asian
1
5.6%
0
0%
0
0%
1
16.7%
0
0%
0
0%
0
0%
0
0%
0
0%
1
16.7%
0
0%
0
0%
0
0%
0
0%
1
16.7%
1
16.7%
1
16.7%
6
5%
Black or African American
7
38.9%
4
66.7%
1
16.7%
1
16.7%
1
16.7%
2
33.3%
3
50%
1
16.7%
2
33.3%
1
16.7%
7
58.3%
3
50%
1
16.7%
1
16.7%
1
16.7%
1
16.7%
1
16.7%
38
31.7%
Native Hawaiian or Other Pacific Islander
0
0%
0
0%
0
0%
0
0%
0
0%
1
16.7%
0
0%
0
0%
0
0%
0
0%
0
0%
1
16.7%
0
0%
0
0%
1
16.7%
0
0%
0
0%
3
2.5%
White
8
44.4%
2
33.3%
5
83.3%
4
66.7%
5
83.3%
3
50%
3
50%
4
66.7%
4
66.7%
3
50%
5
41.7%
2
33.3%
5
83.3%
4
66.7%
3
50%
3
50%
4
66.7%
67
55.8%
Multiracial
2
11.1%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
1
16.7%
0
0%
1
16.7%
0
0%
0
0%
0
0%
1
16.7%
0
0%
1
16.7%
0
0%
6
5%
Region of Enrollment (Count of Participants)
United States
18
100%
6
100%
6
100%
6
100%
6
100%
6
100%
6
100%
6
100%
6
100%
6
100%
12
100%
6
100%
6
100%
6
100%
6
100%
6
100%
6
100%
120
100%
Body Mass Index (BMI) (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]
26.18
(3.741)
27.04
(3.823)
27.24
(3.308)
25.77
(4.359)
23.91
(3.221)
23.23
(2.549)
25.87
(3.332)
23.98
(1.408)
24.47
(2.263)
26.89
(1.468)
25.36
(2.645)
27.26
(3.516)
24.97
(4.563)
25.83
(2.707)
28.64
(2.935)
25.07
(2.124)
27.05
(2.851)
25.82
(3.223)
Smoking History (Count of Participants)
Never Smoked
16
88.9%
5
83.3%
4
66.7%
6
100%
6
100%
5
83.3%
4
66.7%
6
100%
6
100%
5
83.3%
11
91.7%
6
100%
4
66.7%
5
83.3%
5
83.3%
6
100%
6
100%
106
88.3%
Ex-smoker
2
11.1%
1
16.7%
2
33.3%
0
0%
0
0%
1
16.7%
2
33.3%
0
0%
0
0%
1
16.7%
1
8.3%
0
0%
2
33.3%
1
16.7%
1
16.7%
0
0%
0
0%
14
11.7%
Alcohol History (Count of Participants)
Never drank
14
77.8%
5
83.3%
6
100%
4
66.7%
6
100%
6
100%
3
50%
3
50%
4
66.7%
6
100%
9
75%
4
66.7%
5
83.3%
6
100%
4
66.7%
5
83.3%
6
100%
96
80%
Current drinker
4
22.2%
1
16.7%
0
0%
2
33.3%
0
0%
0
0%
3
50%
3
50%
2
33.3%
0
0%
2
16.7%
2
33.3%
0
0%
0
0%
2
33.3%
1
16.7%
0
0%
22
18.3%
Ex- drinker
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
1
8.3%
0
0%
1
16.7%
0
0%
0
0%
0
0%
0
0%
2
1.7%
Alcohol Participant Consumed (Count of Participants)
Count of Participants [Participants]
4
22.2%
1
16.7%
0
0%
2
33.3%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
2
16.7%
2
33.3%
0
0%
0
0%
2
33.3%
1
16.7%
0
0%
14
11.7%
Caffeine Consumption (Count of Participants)
Yes
1
5.6%
3
50%
1
16.7%
1
16.7%
1
16.7%
2
33.3%
0
0%
0
0%
2
33.3%
0
0%
3
25%
2
33.3%
2
33.3%
0
0%
2
33.3%
2
33.3%
1
16.7%
23
19.2%
No
17
94.4%
3
50%
5
83.3%
5
83.3%
5
83.3%
4
66.7%
6
100%
6
100%
4
66.7%
6
100%
9
75%
4
66.7%
4
66.7%
6
100%
4
66.7%
4
66.7%
5
83.3%
97
80.8%
Xanthine Consumption (Count of Participants)
Yes
1
5.6%
3
50%
1
16.7%
0
0%
0
0%
2
33.3%
0
0%
0
0%
2
33.3%
0
0%
3
25%
2
33.3%
2
33.3%
0
0%
2
33.3%
2
33.3%
1
16.7%
21
17.5%
No
17
94.4%
3
50%
5
83.3%
6
100%
6
100%
4
66.7%
6
100%
6
100%
4
66.7%
6
100%
9
75%
4
66.7%
4
66.7%
6
100%
4
66.7%
4
66.7%
5
83.3%
99
82.5%
Female Reproductive Status (Count of Participants)
Postmenopausal
2
11.1%
1
16.7%
0
0%
0
0%
0
0%
0
0%
1
16.7%
0
0%
1
16.7%
0
0%
1
8.3%
0
0%
0
0%
0
0%
0
0%
1
16.7%
0
0%
7
5.8%
Surgically Sterile
0
0%
0
0%
0
0%
0
0%
0
0%
1
16.7%
0
0%
0
0%
0
0%
0
0%
1
8.3%
0
0%
1
16.7%
0
0%
1
16.7%
0
0%
0
0%
4
3.3%
Female of Childbearing Potential
9
50%
1
16.7%
0
0%
3
50%
5
83.3%
2
33.3%
2
33.3%
1
16.7%
1
16.7%
0
0%
3
25%
0
0%
2
33.3%
0
0%
0
0%
0
0%
0
0%
29
24.2%
Not Applicable (Participant was Male)
7
38.9%
4
66.7%
6
100%
3
50%
1
16.7%
3
50%
3
50%
5
83.3%
4
66.7%
6
100%
7
58.3%
6
100%
3
50%
6
100%
5
83.3%
5
83.3%
6
100%
80
66.7%

Outcome Measures

1. Primary Outcome
Title Percentage of Participants Who Experience at Least One Treatment-emergent Adverse Event (TEAE) in Part 1 Single-rising Dose (SRD)
Description 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.
Time Frame First dose of study drug up to and including 30 days after last dose of study drug (Up to 31 days) for Part 1

Outcome Measure Data

Analysis Population Description
Safety Analysis Set was comprised of all participants who received study drug.
Arm/Group Title Part 1 Cohort 1-9: Placebo Part 1 Cohort 1: TAK-020 0.1 mg Part 1 Cohort 2: TAK-020 0.5 mg Part 1 Cohort 3: TAK-020 2.5 mg Part 1 Cohort 4: TAK-020 4.4 mg Part 1 Cohort 5: TAK-020 8.8 mg Part 1 Cohort 6: TAK-020 17.5 mg Part 1 Cohort 7: TAK-020 35 mg Part 1 Cohort 8: TAK-020 70 mg Part 1 Cohort 9: TAK-020 105 mg
Arm/Group Description TAK-020 placebo-matching solution, orally, once on Day 1. TAK-020 0.1 milligram (mg), solution, orally once on Day 1. TAK-020 0.5 mg, solution, orally, once on Day 1 following review of safety, tolerability and pharmacokinetic (PK) data from Cohort 1. TAK-020 2.5 mg, solution, orally once on Day 1 following review of safety, tolerability and PK data from Cohort 2. TAK-020 4.4 mg, solution, orally once on Day 1 following review of safety, tolerability and PK data from Cohort 3. TAK-020 8.8 mg, solution, orally once on Day 1 following review of safety, tolerability and PK data from Cohort 4. TAK-020 17.5 mg, solution, orally once on Day 1 following review of safety, tolerability and PK data from Cohort 5. 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. 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. 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.
Measure Participants 18 6 6 6 6 6 6 6 6 6
Number [percentage of participants]
11.1
61.7%
0
0%
0
0%
16.7
278.3%
0
0%
16.7
278.3%
0
0%
0
0%
50
833.3%
16.7
278.3%
2. Primary Outcome
Title Percentage of Participants With Markedly Abnormal Values (MAV) for Safety Laboratory Findings at Least Once Post-dose in Part 1 (SRD)
Description Safety laboratory tests includes hematology, serum chemistries, and urinalysis.
Time Frame From Day 1 to Day 14 of Part 1

Outcome Measure Data

Analysis Population Description
Safety Analysis Set was comprised of all participants who received study drug.
Arm/Group Title Part 1 Cohort 1-9: Placebo Part 1 Cohort 1: TAK-020 0.1 mg Part 1 Cohort 2: TAK-020 0.5 mg Part 1 Cohort 3: TAK-020 2.5 mg Part 1 Cohort 4: TAK-020 4.4 mg Part 1 Cohort 5: TAK-020 8.8 mg Part 1 Cohort 6: TAK-020 17.5 mg Part 1 Cohort 7: TAK-020 35 mg Part 1 Cohort 8: TAK-020 70 mg Part 1 Cohort 9: TAK-020 105 mg
Arm/Group Description TAK-020 placebo-matching solution, orally, once on Day 1. TAK-020 0.1 milligram (mg), solution, orally once on Day 1. TAK-020 0.5 mg, solution, orally, once on Day 1 following review of safety, tolerability and pharmacokinetic (PK) data from Cohort 1. TAK-020 2.5 mg, solution, orally once on Day 1 following review of safety, tolerability and PK data from Cohort 2. TAK-020 4.4 mg, solution, orally once on Day 1 following review of safety, tolerability and PK data from Cohort 3. TAK-020 8.8 mg, solution, orally once on Day 1 following review of safety, tolerability and PK data from Cohort 4. TAK-020 17.5 mg, solution, orally once on Day 1 following review of safety, tolerability and PK data from Cohort 5. 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. 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. 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.
Measure Participants 18 6 6 6 6 6 6 6 6 6
Hematology
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
Sodium <130 mmol/L
0
0%
0
0%
16.7
278.3%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
Sodium >150 mmol/L
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
Bilirubin Total >34.2 umol/L
0
0%
0
0%
16.7
278.3%
0
0%
0
0%
0
0%
0
0%
16.7
278.3%
0
0%
0
0%
Triglycerides >2.5*ULN
0
0%
0
0%
16.7
278.3%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
Blood Urea Nitrogen (BUN) >10.7 mmol/L
0
0%
0
0%
16.7
278.3%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
3. Primary Outcome
Title Percentage of Participants With MAV for Vital Sign Measurements at Least Once Post-dose in Part 1 (SRD)
Description Vital signs include oral temperature, respiratory rate, sitting blood pressure (after 5 minutes resting) and pulse beats per minute (bpm).
Time Frame From Day 1 to Day 14 of Part 1

Outcome Measure Data

Analysis Population Description
Safety Analysis Set was comprised of all participants who received study drug.
Arm/Group Title Part 1 Cohort 1-9: Placebo Part 1 Cohort 1: TAK-020 0.1 mg Part 1 Cohort 2: TAK-020 0.5 mg Part 1 Cohort 3: TAK-020 2.5 mg Part 1 Cohort 4: TAK-020 4.4 mg Part 1 Cohort 5: TAK-020 8.8 mg Part 1 Cohort 6: TAK-020 17.5 mg Part 1 Cohort 7: TAK-020 35 mg Part 1 Cohort 8: TAK-020 70 mg Part 1 Cohort 9: TAK-020 105 mg
Arm/Group Description TAK-020 placebo-matching solution, orally, once on Day 1. TAK-020 0.1 milligram (mg), solution, orally once on Day 1. TAK-020 0.5 mg, solution, orally, once on Day 1 following review of safety, tolerability and pharmacokinetic (PK) data from Cohort 1. TAK-020 2.5 mg, solution, orally once on Day 1 following review of safety, tolerability and PK data from Cohort 2. TAK-020 4.4 mg, solution, orally once on Day 1 following review of safety, tolerability and PK data from Cohort 3. TAK-020 8.8 mg, solution, orally once on Day 1 following review of safety, tolerability and PK data from Cohort 4. TAK-020 17.5 mg, solution, orally once on Day 1 following review of safety, tolerability and PK data from Cohort 5. 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. 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. 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.
Measure Participants 18 6 6 6 6 6 6 6 6 6
Pulse <50 bpm
11.1
61.7%
0
0%
16.7
278.3%
16.7
278.3%
16.7
278.3%
0
0%
0
0%
0
0%
50
833.3%
0
0%
Pulse >120 bpm
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
Systolic Blood Pressure <85 mm Hg
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
Systolic Blood Pressure >180 mm Hg
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
Diastolic Blood Pressure <50 mm Hg
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
Diastolic Blood Pressure >110 mm Hg
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
Body Temperature <35.6 C
0
0%
0
0%
0
0%
0
0%
16.7
278.3%
0
0%
0
0%
0
0%
0
0%
16.7
278.3%
Body Temperature >37.7 C
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
4. Primary Outcome
Title Percentage of Participants With MAV for Safety Electrocardiogram (ECG) Parameters at Least Once Post-dose in Part 1 (SRD)
Description A standard 12-lead ECG was performed. Change from baseline=CFB.
Time Frame From Day 1 to Day 14 in Part 1

Outcome Measure Data

Analysis Population Description
Safety Analysis Set was comprised of all participants who received study drug.
Arm/Group Title Part 1 Cohort 1-9: Placebo Part 1 Cohort 1: TAK-020 0.1 mg Part 1 Cohort 2: TAK-020 0.5 mg Part 1 Cohort 3: TAK-020 2.5 mg Part 1 Cohort 4: TAK-020 4.4 mg Part 1 Cohort 5: TAK-020 8.8 mg Part 1 Cohort 6: TAK-020 17.5 mg Part 1 Cohort 7: TAK-020 35 mg Part 1 Cohort 8: TAK-020 70 mg Part 1 Cohort 9: TAK-020 105 mg
Arm/Group Description TAK-020 placebo-matching solution, orally, once on Day 1. TAK-020 0.1 milligram (mg), solution, orally once on Day 1. TAK-020 0.5 mg, solution, orally, once on Day 1 following review of safety, tolerability and pharmacokinetic (PK) data from Cohort 1. TAK-020 2.5 mg, solution, orally once on Day 1 following review of safety, tolerability and PK data from Cohort 2. TAK-020 4.4 mg, solution, orally once on Day 1 following review of safety, tolerability and PK data from Cohort 3. TAK-020 8.8 mg, solution, orally once on Day 1 following review of safety, tolerability and PK data from Cohort 4. TAK-020 17.5 mg, solution, orally once on Day 1 following review of safety, tolerability and PK data from Cohort 5. 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. 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. 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.
Measure Participants 18 6 6 6 6 6 6 6 6 6
Heart Rate (beats/min) <50
44.4
246.7%
16.7
278.3%
16.7
278.3%
50.0
833.3%
16.7
278.3%
16.7
278.3%
0
0%
16.7
278.3%
50.0
833.3%
33.3
555%
Heart Rate (beats/min) >120
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
PR Interval (msec[ms]) <=80
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
PR Interval (ms) >= 200
5.6
31.1%
0
0%
0
0%
16.7
278.3%
0
0%
16.7
278.3%
16.7
278.3%
50.0
833.3%
0
0%
33.3
555%
QT Interval (ms) <=300
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
QT Interval (ms) >=460
5.6
31.1%
0
0%
16.7
278.3%
33.3
555%
16.7
278.3%
16.7
278.3%
0
0%
0
0%
16.7
278.3%
0
0%
QTcB Interval (ms) <=300
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
QTcB Interval (ms) ≥500/ ≥30 CFB and ≥450
11.1
61.7%
0
0%
0
0%
0
0%
16.7
278.3%
0
0%
0
0%
0
0%
16.7
278.3%
0
0%
QTcF Interval (ms) <= 300
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
QTcF Interval (ms) ≥500/≥30 CFB and >= 450
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
QRS Interval (ms) <= 80
38.9
216.1%
16.7
278.3%
16.7
278.3%
66.7
1111.7%
83.3
1388.3%
33.3
555%
83.3
1388.3%
0
0%
16.7
278.3%
50.0
833.3%
QRS Interval (ms) >= 180
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
5. Primary Outcome
Title Percentage of Participants Who Experience at Least One Treatment-emergent Adverse Event (TEAE) in Part 2 Multiple-rising Dose (MRD)
Description 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.
Time Frame First dose of study drug up to and including 30 days after last dose of study drug (Up to 39 days) in Part 2

Outcome Measure Data

Analysis Population Description
Safety Analysis Set was comprised of all participants who received study drug.
Arm/Group Title Part 2 Cohort 1-6: Placebo Part 2 Cohort 1: TAK-020 3.75 mg Part 2 Cohort 2: TAK-020 5.75 mg Part 2 Cohort 3: TAK-020 13 mg Part 2 Cohort 4: TAK-020 25 mg Part 2 Cohort 5: TAK-020 45 mg Part 2 Cohort 6: TAK-020 60 mg
Arm/Group Description TAK-020 placebo-matching solution, orally, once on Day 1 and Days 3 to 9. 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. 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. 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. 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. 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. 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.
Measure Participants 12 6 6 6 6 6 6
Number [percentage of participants]
41.7
231.7%
16.7
278.3%
50.0
833.3%
50.0
833.3%
33.3
555%
16.7
278.3%
16.7
278.3%
6. Primary Outcome
Title Percentage of Participants With MAV for Safety Laboratory Findings at Least Once Post-dose in Part 2 (MRD)
Description Safety laboratory tests include hematology, and serum chemistries.
Time Frame From Day 1 to Day 17 in Part 2

Outcome Measure Data

Analysis Population Description
Safety Analysis Set included all participants who received study drug.
Arm/Group Title Part 2 Cohort 1-6: Placebo Part 2 Cohort 1: TAK-020 3.75 mg Part 2 Cohort 2: TAK-020 5.75 mg Part 2 Cohort 3: TAK-020 13 mg Part 2 Cohort 4: TAK-020 25 mg Part 2 Cohort 5: TAK-020 45 mg Part 2 Cohort 6: TAK-020 60 mg
Arm/Group Description TAK-020 placebo-matching solution, orally, once on Day 1 and Days 3 to 9. 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. 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. 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. 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. 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. 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.
Measure Participants 12 6 6 6 6 6 6
Hematology
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
Creatine Kinase >5*ULN (U/L)
0
0%
16.7
278.3%
0
0%
0
0%
0
0%
0
0%
16.7
278.3%
Lipase >3*ULN (U/L)
0
0%
0
0%
0
0%
0
0%
16.7
278.3%
0
0%
0
0%
7. Primary Outcome
Title Percentage of Participants With MAV for Vital Sign Measurements at Least Once Post-dose in Part 2 (MRD)
Description Vital signs include oral temperature respiratory rate, sitting blood pressure (after 5 minutes resting) and pulse (bpm).
Time Frame From Day 1 to Day 17 in Part 2

Outcome Measure Data

Analysis Population Description
Safety Analysis Set included all participants who received study drug.
Arm/Group Title Part 2 Cohort 1-6: Placebo Part 2 Cohort 1: TAK-020 3.75 mg Part 2 Cohort 2: TAK-020 5.75 mg Part 2 Cohort 3: TAK-020 13 mg Part 2 Cohort 4: TAK-020 25 mg Part 2 Cohort 5: TAK-020 45 mg Part 2 Cohort 6: TAK-020 60 mg
Arm/Group Description TAK-020 placebo-matching solution, orally, once on Day 1 and Days 3 to 9. 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. 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. 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. 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. 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. 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.
Measure Participants 12 6 6 6 6 6 6
Pulse <50 bpm
8.3
46.1%
0
0%
16.7
278.3%
0
0%
16.7
278.3%
0
0%
16.7
278.3%
Pulse >120 bpm
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
16.7
278.3%
Systolic Blood Pressure <85 mm Hg
0
0%
0
0%
16.7
278.3%
0
0%
0
0%
0
0%
0
0%
Systolic Blood Pressure >180 mm Hg
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
Diastolic Blood Pressure <50 mm Hg
0
0%
0
0%
0
0%
0
0%
0
0%
16.7
278.3%
0
0%
Diastolic Blood Pressure >110 mm Hg
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
Body Temperature <35.6 C
33.3
185%
16.7
278.3%
33.3
555%
33.3
555%
16.7
278.3%
16.7
278.3%
0
0%
Body Temperature >37.7 C
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
16.7
278.3%
8. Primary Outcome
Title Percentage of Participants With MAV for Safety ECG Parameters at Least Once Post-dose in Part 2 (MRD)
Description A standard 12-lead ECG was performed.
Time Frame From Day 1 to Day 17 in Part 2

Outcome Measure Data

Analysis Population Description
Safety Analysis Set included all participants who received study drug.
Arm/Group Title Part 2 Cohort 1-6: Placebo Part 2 Cohort 1: TAK-020 3.75 mg Part 2 Cohort 2: TAK-020 5.75 mg Part 2 Cohort 3: TAK-020 13 mg Part 2 Cohort 4: TAK-020 25 mg Part 2 Cohort 5: TAK-020 45 mg Part 2 Cohort 6: TAK-020 60 mg
Arm/Group Description TAK-020 placebo-matching solution, orally, once on Day 1 and Days 3 to 9. 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. 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. 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. 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. 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. 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.
Measure Participants 12 6 6 6 6 6 6
Heart Rate (beats/min) <50
16.7
92.8%
16.7
278.3%
16.7
278.3%
50.0
833.3%
50.0
833.3%
16.7
278.3%
16.7
278.3%
Heart Rate (beats/min) >120
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
PR Interval (msec) <=80
16.7
92.8%
16.7
278.3%
0
0%
0
0%
0
0%
0
0%
0
0%
PR Interval (msec) >=200
16.7
92.8%
16.7
278.3%
0
0%
0
0%
16.7
278.3%
0
0%
16.7
278.3%
QT Interval (msec) <=300
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
QT Interval (msec) >=460
16.7
92.8%
0
0%
0
0%
16.7
278.3%
33.3
555%
16.7
278.3%
16.7
278.3%
QTcB Interval (msec) <=300
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
QTcB Interval (ms) ≥500/≥ 30 CFB and ≥450
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
QTcF Interval (msec) <=300
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
QTcF Interval (ms) ≥500/≥30 CFB and >= 450
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
QRS Interval (msec) <=80
50.0
277.8%
33.3
555%
50.0
833.3%
16.7
278.3%
0
0%
16.7
278.3%
50.0
833.3%
QRS Interval (msec) >=180
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
9. Secondary Outcome
Title Cmax: Maximum Observed Plasma Concentration for TAK-020 in Part 1 (SRD)
Description
Time Frame Pre-dose and multiple timepoints (up to 96 hours) post-dose in Part 1

Outcome Measure Data

Analysis Population Description
Pharmacokinetic set included all participants who received study drug and had at least one measurable plasma concentration or amount of drug in the urine.
Arm/Group Title Part 1 Cohort 1: TAK-020 0.1 mg Part 1 Cohort 2: TAK-020 0.5 mg Part 1 Cohort 3: TAK-020 2.5 mg Part 1 Cohort 4: TAK-020 4.4 mg Part 1 Cohort 5: TAK-020 8.8 mg Part 1 Cohort 6: TAK-020 17.5 mg Part 1 Cohort 7: TAK-020 35 mg Part 1 Cohort 8: TAK-020 70 mg Part 1 Cohort 9: TAK-020 105 mg
Arm/Group Description TAK-020 0.1 milligram (mg), solution, orally once on Day 1. TAK-020 0.5 mg, solution, orally, once on Day 1 following review of safety, tolerability and pharmacokinetic (PK) data from Cohort 1. TAK-020 2.5 mg, solution, orally once on Day 1 following review of safety, tolerability and PK data from Cohort 2. TAK-020 4.4 mg, solution, orally once on Day 1 following review of safety, tolerability and PK data from Cohort 3. TAK-020 8.8 mg, solution, orally once on Day 1 following review of safety, tolerability and PK data from Cohort 4. TAK-020 17.5 mg, solution, orally once on Day 1 following review of safety, tolerability and PK data from Cohort 5. 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. 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. 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.
Measure Participants 6 6 6 6 6 6 6 6 6
Geometric Mean (Geometric Coefficient of Variation) [ng/mL]
0.4631
(36.3)
1.5529
(25.2)
13.5475
(40.7)
24.2013
(29.5)
42.8329
(43.3)
105.7708
(33.3)
155.6549
(31.8)
446.1922
(50.9)
345.4612
(51.6)
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part 1 Cohort 1-9: Placebo, Part 1 Cohort 1: TAK-020 0.1 mg, Part 1 Cohort 2: TAK-020 0.5 mg, Part 1 Cohort 3: TAK-020 2.5 mg, Part 1 Cohort 4: TAK-020 4.4 mg, Part 1 Cohort 5: TAK-020 8.8 mg, Part 1 Cohort 6: TAK-020 17.5 mg, Part 1 Cohort 7: TAK-020 35 mg, Part 1 Cohort 8: TAK-020 70 mg
Comments
Type of Statistical Test Equivalence
Comments 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.
Statistical Test of Hypothesis p-Value 0.465
Comments
Method Power Model
Comments
Method of Estimation Estimation Parameter Slope
Estimated Value 1.0195
Confidence Interval (2-Sided) 90%
0.9752 to 1.0637
Parameter Dispersion Type:
Value:
Estimation Comments
10. Secondary Outcome
Title Cmax: Maximum Observed Plasma Concentration for TAK-020 in Part 2 (MRD)
Description
Time Frame 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

Outcome Measure Data

Analysis Population Description
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.
Arm/Group Title Part 2 Cohort 1: TAK-020 3.75 mg Part 2 Cohort 2: TAK-020 5.75 mg Part 2 Cohort 3: TAK-020 13 mg Part 2 Cohort 4: TAK-020 25 mg Part 2 Cohort 5: TAK-020 45 mg Part 2 Cohort 6: TAK-020 60 mg
Arm/Group Description 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. 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. 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. 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. 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. 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.
Measure Participants 6 6 6 6 6 6
Day 1
16.4167
(46.7)
40.3204
(14.4)
64.7590
(73.3)
161.9015
(47.1)
300.8684
(33.3)
423.8189
(46.9)
Day 9
17.6976
(34.2)
39.6336
(17.7)
63.6636
(34.5)
160.6945
(33.0)
279.6237
(34.1)
433.4214
(43.7)
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part 1 Cohort 1-9: Placebo, Part 1 Cohort 1: TAK-020 0.1 mg, Part 1 Cohort 2: TAK-020 0.5 mg, Part 1 Cohort 3: TAK-020 2.5 mg, Part 1 Cohort 4: TAK-020 4.4 mg, Part 1 Cohort 5: TAK-020 8.8 mg
Comments Day 1
Type of Statistical Test Equivalence
Comments 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.
Statistical Test of Hypothesis p-Value 0.126
Comments
Method Power Model
Comments
Method of Estimation Estimation Parameter Slope
Estimated Value 1.1124
Confidence Interval (2-Sided) 90%
0.9913 to 1.2336
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Part 1 Cohort 1-9: Placebo, Part 1 Cohort 1: TAK-020 0.1 mg, Part 1 Cohort 2: TAK-020 0.5 mg, Part 1 Cohort 3: TAK-020 2.5 mg, Part 1 Cohort 4: TAK-020 4.4 mg, Part 1 Cohort 5: TAK-020 8.8 mg
Comments Day 9
Type of Statistical Test Equivalence
Comments 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.
Statistical Test of Hypothesis p-Value 0.114
Comments
Method Power Model
Comments
Method of Estimation Estimation Parameter Slope
Estimated Value 1.0900
Confidence Interval (2-Sided) 90%
0.9962 to 1.1838
Parameter Dispersion Type:
Value:
Estimation Comments
11. Secondary Outcome
Title Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-020 in Part 1 (SRD)
Description
Time Frame Pre-dose and multiple timepoints (up to 96 hours) post-dose in Part 1

Outcome Measure Data

Analysis Population Description
Pharmacokinetic set included all participants who received study drug and had at least one measurable plasma concentration or amount of drug in the urine.
Arm/Group Title Part 1 Cohort 1: TAK-020 0.1 mg Part 1 Cohort 2: TAK-020 0.5 mg Part 1 Cohort 3: TAK-020 2.5 mg Part 1 Cohort 4: TAK-020 4.4 mg Part 1 Cohort 5: TAK-020 8.8 mg Part 1 Cohort 6: TAK-020 17.5 mg Part 1 Cohort 7: TAK-020 35 mg Part 1 Cohort 8: TAK-020 70 mg Part 1 Cohort 9: TAK-020 105 mg
Arm/Group Description TAK-020 0.1 milligram (mg), solution, orally once on Day 1. TAK-020 0.5 mg, solution, orally, once on Day 1 following review of safety, tolerability and pharmacokinetic (PK) data from Cohort 1. TAK-020 2.5 mg, solution, orally once on Day 1 following review of safety, tolerability and PK data from Cohort 2. TAK-020 4.4 mg, solution, orally once on Day 1 following review of safety, tolerability and PK data from Cohort 3. TAK-020 8.8 mg, solution, orally once on Day 1 following review of safety, tolerability and PK data from Cohort 4. TAK-020 17.5 mg, solution, orally once on Day 1 following review of safety, tolerability and PK data from Cohort 5. 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. 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. 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.
Measure Participants 6 6 6 6 6 6 6 6 6
Median (Full Range) [hr]
0.750
0.700
0.745
0.825
0.780
1.010
0.630
0.725
0.750
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part 1 Cohort 1-9: Placebo, Part 1 Cohort 1: TAK-020 0.1 mg, Part 1 Cohort 2: TAK-020 0.5 mg, Part 1 Cohort 3: TAK-020 2.5 mg, Part 1 Cohort 4: TAK-020 4.4 mg, Part 1 Cohort 5: TAK-020 8.8 mg, Part 1 Cohort 6: TAK-020 17.5 mg, Part 1 Cohort 7: TAK-020 35 mg, Part 1 Cohort 8: TAK-020 70 mg
Comments
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.5402
Comments
Method ANOVA
Comments Statistical analysis results were obtained using Analysis of Variance (ANOVA) with dose level as a fixed effect.
12. Secondary Outcome
Title Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-020 in Part 2 (MRD)
Description
Time Frame 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

Outcome Measure Data

Analysis Population Description
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.
Arm/Group Title Part 2 Cohort 1: TAK-020 3.75 mg Part 2 Cohort 2: TAK-020 5.75 mg Part 2 Cohort 3: TAK-020 13 mg Part 2 Cohort 4: TAK-020 25 mg Part 2 Cohort 5: TAK-020 45 mg Part 2 Cohort 6: TAK-020 60 mg
Arm/Group Description 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. 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. 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. 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. 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. 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.
Measure Participants 6 6 6 6 6 6
Day 1
0.750
0.750
0.750
0.750
0.500
0.640
Day 9
0.750
1.000
0.750
0.750
0.750
0.875
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part 1 Cohort 1-9: Placebo, Part 1 Cohort 1: TAK-020 0.1 mg, Part 1 Cohort 2: TAK-020 0.5 mg, Part 1 Cohort 3: TAK-020 2.5 mg, Part 1 Cohort 4: TAK-020 4.4 mg, Part 1 Cohort 5: TAK-020 8.8 mg
Comments Day 1
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.7824
Comments
Method ANOVA
Comments Statistical analysis results were obtained using ANOVA with dose level as a fixed effect.
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Part 1 Cohort 1-9: Placebo, Part 1 Cohort 1: TAK-020 0.1 mg, Part 1 Cohort 2: TAK-020 0.5 mg, Part 1 Cohort 3: TAK-020 2.5 mg, Part 1 Cohort 4: TAK-020 4.4 mg, Part 1 Cohort 5: TAK-020 8.8 mg
Comments Day 9
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.4056
Comments
Method ANOVA
Comments Statistical analysis results were obtained using ANOVA with dose level as a fixed effect.
13. Secondary Outcome
Title AUC24: Area Under the Plasma Concentration-time Curve From Time 0 to Time 24 Hours for TAK-020 in Part 1 (SRD)
Description
Time Frame Pre-dose and multiple timepoints (up to 24 hours) post-dose in Part 1

Outcome Measure Data

Analysis Population Description
Pharmacokinetic set included all participants who received study drug and had at least one measurable plasma concentration or amount of drug in the urine.
Arm/Group Title Part 1 Cohort 1: TAK-020 0.1 mg Part 1 Cohort 2: TAK-020 0.5 mg Part 1 Cohort 3: TAK-020 2.5 mg Part 1 Cohort 4: TAK-020 4.4 mg Part 1 Cohort 5: TAK-020 8.8 mg Part 1 Cohort 6: TAK-020 17.5 mg Part 1 Cohort 7: TAK-020 35 mg Part 1 Cohort 8: TAK-020 70 mg Part 1 Cohort 9: TAK-020 105 mg
Arm/Group Description TAK-020 0.1 milligram (mg), solution, orally once on Day 1. TAK-020 0.5 mg, solution, orally, once on Day 1 following review of safety, tolerability and pharmacokinetic (PK) data from Cohort 1. TAK-020 2.5 mg, solution, orally once on Day 1 following review of safety, tolerability and PK data from Cohort 2. TAK-020 4.4 mg, solution, orally once on Day 1 following review of safety, tolerability and PK data from Cohort 3. TAK-020 8.8 mg, solution, orally once on Day 1 following review of safety, tolerability and PK data from Cohort 4. TAK-020 17.5 mg, solution, orally once on Day 1 following review of safety, tolerability and PK data from Cohort 5. 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. 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. 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.
Measure Participants 6 6 6 6 6 6 6 6 6
Geometric Mean (Geometric Coefficient of Variation) [ng*hr/mL]
0.7599
(45.6)
3.6691
(28.2)
29.7502
(48.1)
63.1772
(31.3)
98.8228
(34.6)
272.3381
(39.5)
372.5881
(35.2)
1009.0958
(32.3)
875.0011
(15.9)
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part 1 Cohort 1-9: Placebo, Part 1 Cohort 1: TAK-020 0.1 mg, Part 1 Cohort 2: TAK-020 0.5 mg, Part 1 Cohort 3: TAK-020 2.5 mg, Part 1 Cohort 4: TAK-020 4.4 mg, Part 1 Cohort 5: TAK-020 8.8 mg, Part 1 Cohort 6: TAK-020 17.5 mg, Part 1 Cohort 7: TAK-020 35 mg, Part 1 Cohort 8: TAK-020 70 mg
Comments
Type of Statistical Test Equivalence
Comments 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.
Statistical Test of Hypothesis p-Value 0.019
Comments
Method Power Model
Comments
Method of Estimation Estimation Parameter Slope
Estimated Value 1.0606
Confidence Interval (2-Sided) 90%
1.0187 to 1.1026
Parameter Dispersion Type:
Value:
Estimation Comments
14. Secondary Outcome
Title AUC24: Area Under the Plasma Concentration-time Curve From Time 0 to Time 24 Hours for TAK-020 in Part 2 (MRD)
Description
Time Frame 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

Outcome Measure Data

Analysis Population Description
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.
Arm/Group Title Part 2 Cohort 1: TAK-020 3.75 mg Part 2 Cohort 2: TAK-020 5.75 mg Part 2 Cohort 3: TAK-020 13 mg Part 2 Cohort 4: TAK-020 25 mg Part 2 Cohort 5: TAK-020 45 mg Part 2 Cohort 6: TAK-020 60 mg
Arm/Group Description 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. 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. 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. 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. 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. 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.
Measure Participants 6 6 6 6 6 6
Day 1
34.6177
(50.4)
86.4177
(18.5)
148.6319
(64.8)
389.8000
(43.0)
576.1987
(31.5)
808.3223
(39.1)
Day 9
39.0653
(43.9)
100.2960
(21.2)
147.1828
(47.8)
400.5548
(27.6)
648.9853
(25.3)
1011.2702
(44.9)
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part 1 Cohort 1-9: Placebo, Part 1 Cohort 1: TAK-020 0.1 mg, Part 1 Cohort 2: TAK-020 0.5 mg, Part 1 Cohort 3: TAK-020 2.5 mg, Part 1 Cohort 4: TAK-020 4.4 mg, Part 1 Cohort 5: TAK-020 8.8 mg
Comments Day 1
Type of Statistical Test Equivalence
Comments 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.
Statistical Test of Hypothesis p-Value 0.258
Comments
Method Power Model
Comments
Method of Estimation Estimation Parameter Slope
Estimated Value 1.0789
Confidence Interval (2-Sided) 90%
0.9628 to 1.1950
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Part 1 Cohort 1-9: Placebo, Part 1 Cohort 1: TAK-020 0.1 mg, Part 1 Cohort 2: TAK-020 0.5 mg, Part 1 Cohort 3: TAK-020 2.5 mg, Part 1 Cohort 4: TAK-020 4.4 mg, Part 1 Cohort 5: TAK-020 8.8 mg
Comments Day 9
Type of Statistical Test Equivalence
Comments 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.
Statistical Test of Hypothesis p-Value 0.144
Comments
Method Power Model
Comments
Method of Estimation Estimation Parameter Slope
Estimated Value 1.0929
Confidence Interval (2-Sided) 90%
0.9878 to 1.1980
Parameter Dispersion Type:
Value:
Estimation Comments
15. Secondary Outcome
Title 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)
Description
Time Frame Pre-dose and multiple timepoints (up to 24 hours) post-dose in Part 1

Outcome Measure Data

Analysis Population Description
Pharmacokinetic set included all participants who received study drug and had at least one measurable plasma concentration or amount of drug in the urine.
Arm/Group Title Part 1 Cohort 1: TAK-020 0.1 mg Part 1 Cohort 2: TAK-020 0.5 mg Part 1 Cohort 3: TAK-020 2.5 mg Part 1 Cohort 4: TAK-020 4.4 mg Part 1 Cohort 5: TAK-020 8.8 mg Part 1 Cohort 6: TAK-020 17.5 mg Part 1 Cohort 7: TAK-020 35 mg Part 1 Cohort 8: TAK-020 70 mg Part 1 Cohort 9: TAK-020 105 mg
Arm/Group Description TAK-020 0.1 milligram (mg), solution, orally once on Day 1. TAK-020 0.5 mg, solution, orally, once on Day 1 following review of safety, tolerability and pharmacokinetic (PK) data from Cohort 1. TAK-020 2.5 mg, solution, orally once on Day 1 following review of safety, tolerability and PK data from Cohort 2. TAK-020 4.4 mg, solution, orally once on Day 1 following review of safety, tolerability and PK data from Cohort 3. TAK-020 8.8 mg, solution, orally once on Day 1 following review of safety, tolerability and PK data from Cohort 4. TAK-020 17.5 mg, solution, orally once on Day 1 following review of safety, tolerability and PK data from Cohort 5. 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. 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. 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.
Measure Participants 6 6 6 6 6 6 6 6 6
Geometric Mean (Geometric Coefficient of Variation) [ng*hr/mL/mg]
7.5994
(45.6)
7.3382
(28.2)
11.9001
(48.1)
14.3584
(31.3)
11.2299
(34.6)
15.5622
(39.5)
10.6454
(35.2)
14.4157
(32.3)
8.3333
(15.9)
16. Secondary Outcome
Title 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)
Description
Time Frame 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

Outcome Measure Data

Analysis Population Description
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.
Arm/Group Title Part 2 Cohort 1: TAK-020 3.75 mg Part 2 Cohort 2: TAK-020 5.75 mg Part 2 Cohort 3: TAK-020 13 mg Part 2 Cohort 4: TAK-020 25 mg Part 2 Cohort 5: TAK-020 45 mg Part 2 Cohort 6: TAK-020 60 mg
Arm/Group Description 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. 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. 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. 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. 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. 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.
Measure Participants 6 6 6 6 6 6
Day 1
9.2314
(50.4)
15.0292
(18.5)
11.4332
(64.8)
15.5920
(43.0)
12.8044
(31.5)
13.4720
(39.1)
Day 9
10.4174
(43.9)
17.4428
(21.2)
11.3218
(47.8)
16.0222
(27.6)
14.4219
(25.3)
16.8545
(44.9)
17. Secondary Outcome
Title AUCt: Area Under the Plasma Concentration-time Curve From Time 0 to Time t Over the Dosing Interval for TAK-020 (SRD)
Description
Time Frame Pre-dose and multiple timepoints (up to 96 hours) post-dose in Part 1

Outcome Measure Data

Analysis Population Description
Pharmacokinetic set included all participants who received study drug and had at least one measurable plasma concentration or amount of drug in the urine.
Arm/Group Title Part 1 Cohort 1: TAK-020 0.1 mg Part 1 Cohort 2: TAK-020 0.5 mg Part 1 Cohort 3: TAK-020 2.5 mg Part 1 Cohort 4: TAK-020 4.4 mg Part 1 Cohort 5: TAK-020 8.8 mg Part 1 Cohort 6: TAK-020 17.5 mg Part 1 Cohort 7: TAK-020 35 mg Part 1 Cohort 8: TAK-020 70 mg Part 1 Cohort 9: TAK-020 105 mg
Arm/Group Description TAK-020 0.1 milligram (mg), solution, orally once on Day 1. TAK-020 0.5 mg, solution, orally, once on Day 1 following review of safety, tolerability and pharmacokinetic (PK) data from Cohort 1. TAK-020 2.5 mg, solution, orally once on Day 1 following review of safety, tolerability and PK data from Cohort 2. TAK-020 4.4 mg, solution, orally once on Day 1 following review of safety, tolerability and PK data from Cohort 3. TAK-020 8.8 mg, solution, orally once on Day 1 following review of safety, tolerability and PK data from Cohort 4. TAK-020 17.5 mg, solution, orally once on Day 1 following review of safety, tolerability and PK data from Cohort 5. 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. 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. 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.
Measure Participants 6 6 6 6 6 6 6 6 6
Geometric Mean (Geometric Coefficient of Variation) [ng*hr/mL]
0.6674
(50.3)
3.5250
(30.3)
29.4206
(48.1)
62.4593
(31.9)
98.6610
(34.4)
273.0083
(40.0)
378.3179
(35.5)
1024.5599
(32.5)
903.9858
(14.6)
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part 1 Cohort 1-9: Placebo, Part 1 Cohort 1: TAK-020 0.1 mg, Part 1 Cohort 2: TAK-020 0.5 mg, Part 1 Cohort 3: TAK-020 2.5 mg, Part 1 Cohort 4: TAK-020 4.4 mg, Part 1 Cohort 5: TAK-020 8.8 mg, Part 1 Cohort 6: TAK-020 17.5 mg, Part 1 Cohort 7: TAK-020 35 mg, Part 1 Cohort 8: TAK-020 70 mg
Comments
Type of Statistical Test Equivalence
Comments 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.
Statistical Test of Hypothesis p-Value 0.003
Comments
Method Power Model
Comments
Method of Estimation Estimation Parameter Slope
Estimated Value 1.0799
Confidence Interval (2-Sided) 90%
1.0371 to 1.1227
Parameter Dispersion Type:
Value:
Estimation Comments
18. Secondary Outcome
Title 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)
Description
Time Frame 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

Outcome Measure Data

Analysis Population Description
Pharmacokinetic set included all participants who received study drug and had at least one measurable plasma concentration or amount of drug in the urine.
Arm/Group Title Part 2 Cohort 1: TAK-020 3.75 mg Part 2 Cohort 2: TAK-020 5.75 mg Part 2 Cohort 3: TAK-020 13 mg Part 2 Cohort 4: TAK-020 25 mg Part 2 Cohort 5: TAK-020 45 mg Part 2 Cohort 6: TAK-020 60 mg
Arm/Group Description 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. 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. 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. 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. 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. 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.
Measure Participants 6 6 6 6 6 6
Geometric Mean (Geometric Coefficient of Variation) [ng*hr/mL]
34.1425
(50.2)
85.7708
(18.3)
148.6319
(64.8)
391.5478
(43.2)
583.7178
(32.2)
823.3525
(39.0)
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part 1 Cohort 1-9: Placebo, Part 1 Cohort 1: TAK-020 0.1 mg, Part 1 Cohort 2: TAK-020 0.5 mg, Part 1 Cohort 3: TAK-020 2.5 mg, Part 1 Cohort 4: TAK-020 4.4 mg, Part 1 Cohort 5: TAK-020 8.8 mg
Comments
Type of Statistical Test Equivalence
Comments 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.
Statistical Test of Hypothesis p-Value 0.201
Comments
Method Power Model
Comments
Method of Estimation Estimation Parameter Slope
Estimated Value 1.0897
Confidence Interval (2-Sided) 90%
0.9735 to 1.2060
Parameter Dispersion Type:
Value:
Estimation Comments
19. Secondary Outcome
Title 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)
Description
Time Frame Pre-dose and multiple timepoints (up to 96 hours) post-dose in Part 1

Outcome Measure Data

Analysis Population Description
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.
Arm/Group Title Part 1 Cohort 1: TAK-020 0.1 mg Part 1 Cohort 2: TAK-020 0.5 mg Part 1 Cohort 3: TAK-020 2.5 mg Part 1 Cohort 4: TAK-020 4.4 mg Part 1 Cohort 5: TAK-020 8.8 mg Part 1 Cohort 6: TAK-020 17.5 mg Part 1 Cohort 7: TAK-020 35 mg Part 1 Cohort 8: TAK-020 70 mg Part 1 Cohort 9: TAK-020 105 mg
Arm/Group Description TAK-020 0.1 milligram (mg), solution, orally once on Day 1. TAK-020 0.5 mg, solution, orally, once on Day 1 following review of safety, tolerability and pharmacokinetic (PK) data from Cohort 1. TAK-020 2.5 mg, solution, orally once on Day 1 following review of safety, tolerability and PK data from Cohort 2. TAK-020 4.4 mg, solution, orally once on Day 1 following review of safety, tolerability and PK data from Cohort 3. TAK-020 8.8 mg, solution, orally once on Day 1 following review of safety, tolerability and PK data from Cohort 4. TAK-020 17.5 mg, solution, orally once on Day 1 following review of safety, tolerability and PK data from Cohort 5. 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. 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. 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.
Measure Participants 6 6 6 6 6 6 6 6 6
Geometric Mean (Geometric Coefficient of Variation) [ng*hr/mL]
1.3733
(32.1)
3.8341
(26.8)
29.9808
(47.4)
69.3298
(24.2)
100.2928
(34.3)
275.1708
(39.6)
380.2423
(35.2)
1030.7508
(32.3)
907.7704
(14.5)
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part 1 Cohort 1-9: Placebo, Part 1 Cohort 1: TAK-020 0.1 mg, Part 1 Cohort 2: TAK-020 0.5 mg, Part 1 Cohort 3: TAK-020 2.5 mg, Part 1 Cohort 4: TAK-020 4.4 mg, Part 1 Cohort 5: TAK-020 8.8 mg, Part 1 Cohort 6: TAK-020 17.5 mg, Part 1 Cohort 7: TAK-020 35 mg, Part 1 Cohort 8: TAK-020 70 mg
Comments
Type of Statistical Test Equivalence
Comments 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.
Statistical Test of Hypothesis p-Value 0.490
Comments
Method Power Model
Comments
Method of Estimation Estimation Parameter Slope
Estimated Value 1.0188
Confidence Interval (2-Sided) 90%
0.9734 to 1.0642
Parameter Dispersion Type:
Value:
Estimation Comments
20. Secondary Outcome
Title 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)
Description
Time Frame Pre-dose and multiple timepoints (up to 48 hours) post-dose on Day 1 in Part 2

Outcome Measure Data

Analysis Population Description
Pharmacokinetic set included all participants who received study drug and had at least one measurable plasma concentration or amount of drug in the urine.
Arm/Group Title Part 2 Cohort 1: TAK-020 3.75 mg Part 2 Cohort 2: TAK-020 5.75 mg Part 2 Cohort 3: TAK-020 13 mg Part 2 Cohort 4: TAK-020 25 mg Part 2 Cohort 5: TAK-020 45 mg Part 2 Cohort 6: TAK-020 60 mg
Arm/Group Description 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. 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. 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. 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. 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. 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.
Measure Participants 6 6 6 6 6 6
Geometric Mean (Geometric Coefficient of Variation) [ng*hr/mL]
34.8469
(49.8)
86.7892
(18.1)
149.9419
(64.5)
393.8737
(43.2)
587.4204
(31.8)
825.6238
(38.9)
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part 1 Cohort 1-9: Placebo, Part 1 Cohort 1: TAK-020 0.1 mg, Part 1 Cohort 2: TAK-020 0.5 mg, Part 1 Cohort 3: TAK-020 2.5 mg, Part 1 Cohort 4: TAK-020 4.4 mg, Part 1 Cohort 5: TAK-020 8.8 mg
Comments
Type of Statistical Test Equivalence
Comments 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.
Statistical Test of Hypothesis p-Value 0.224
Comments
Method Power Model
Comments
Method of Estimation Estimation Parameter Slope
Estimated Value 1.0846
Confidence Interval (2-Sided) 90%
0.9690 to 1.2002
Parameter Dispersion Type:
Value:
Estimation Comments
21. Secondary Outcome
Title Rac(AUC): Accumulation Ratio Based on AUC Calculated as AUC24 at Steady State/AUC24 After a Single Dose for TAK-020 (MRD)
Description
Time Frame Pre-dose and multiple timepoints (up to 24 hours) post-dose on Day 9 in Part 2

Outcome Measure Data

Analysis Population Description
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.
Arm/Group Title Part 2 Cohort 1: TAK-020 3.75 mg Part 2 Cohort 2: TAK-020 5.75 mg Part 2 Cohort 3: TAK-020 13 mg Part 2 Cohort 4: TAK-020 25 mg Part 2 Cohort 5: TAK-020 45 mg Part 2 Cohort 6: TAK-020 60 mg
Arm/Group Description 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. 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. 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. 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. 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. 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.
Measure Participants 6 6 6 6 6 6
Geometric Mean (Geometric Coefficient of Variation) [ratio]
1.1285
(21.9)
1.1606
(8.9)
0.9903
(18.7)
1.0628
(23.3)
1.1263
(10.7)
1.2511
(15.6)
22. Secondary Outcome
Title Rac(Cmax): Accumulation Ratio Based on Cmax Calculated as Cmax at Steady State/Cmax After a Single Dose for TAK-020 (MRD)
Description
Time Frame Pre-dose and multiple timepoints (up to 24 hours) post-dose on Day 9 in Part 2

Outcome Measure Data

Analysis Population Description
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.
Arm/Group Title Part 2 Cohort 1: TAK-020 3.75 mg Part 2 Cohort 2: TAK-020 5.75 mg Part 2 Cohort 3: TAK-020 13 mg Part 2 Cohort 4: TAK-020 25 mg Part 2 Cohort 5: TAK-020 45 mg Part 2 Cohort 6: TAK-020 60 mg
Arm/Group Description 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. 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. 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. 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. 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. 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.
Measure Participants 6 6 6 6 6 6
Geometric Mean (Geometric Coefficient of Variation) [ratio]
1.0780
(22.9)
0.9830
(10.5)
0.9831
(39.4)
0.9379
(29.2)
0.9294
(16.3)
1.0227
(29.5)
23. Secondary Outcome
Title Cmax/D: Maximum Observed Plasma Concentration Divided by TAK-020 Dose for TAK-020 (SRD)
Description
Time Frame Pre-dose and multiple timepoints (up to 96 hours) post-dose in Part 1

Outcome Measure Data

Analysis Population Description
Pharmacokinetic set included all participants who received study drug and had at least one measurable plasma concentration or amount of drug in the urine.
Arm/Group Title Part 1 Cohort 1: TAK-020 0.1 mg Part 1 Cohort 2: TAK-020 0.5 mg Part 1 Cohort 3: TAK-020 2.5 mg Part 1 Cohort 4: TAK-020 4.4 mg Part 1 Cohort 5: TAK-020 8.8 mg Part 1 Cohort 6: TAK-020 17.5 mg Part 1 Cohort 7: TAK-020 35 mg Part 1 Cohort 8: TAK-020 70 mg Part 1 Cohort 9: TAK-020 105 mg
Arm/Group Description TAK-020 0.1 milligram (mg), solution, orally once on Day 1. TAK-020 0.5 mg, solution, orally, once on Day 1 following review of safety, tolerability and pharmacokinetic (PK) data from Cohort 1. TAK-020 2.5 mg, solution, orally once on Day 1 following review of safety, tolerability and PK data from Cohort 2. TAK-020 4.4 mg, solution, orally once on Day 1 following review of safety, tolerability and PK data from Cohort 3. TAK-020 8.8 mg, solution, orally once on Day 1 following review of safety, tolerability and PK data from Cohort 4. TAK-020 17.5 mg, solution, orally once on Day 1 following review of safety, tolerability and PK data from Cohort 5. 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. 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. 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.
Measure Participants 6 6 6 6 6 6 6 6 6
Geometric Mean (Geometric Coefficient of Variation) [ng/mL/mg]
4.6312
(36.3)
3.1058
(25.2)
5.4190
(40.7)
5.5003
(29.5)
4.8674
(43.3)
6.0440
(33.3)
4.4473
(31.8)
6.3742
(50.9)
3.2901
(51.6)
24. Secondary Outcome
Title Cmax/D: Maximum Observed Plasma Concentration Divided by TAK-020 Dose for TAK-020 (MRD)
Description
Time Frame 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

Outcome Measure Data

Analysis Population Description
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.
Arm/Group Title Part 2 Cohort 1: TAK-020 3.75 mg Part 2 Cohort 2: TAK-020 5.75 mg Part 2 Cohort 3: TAK-020 13 mg Part 2 Cohort 4: TAK-020 25 mg Part 2 Cohort 5: TAK-020 45 mg Part 2 Cohort 6: TAK-020 60 mg
Arm/Group Description 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. 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. 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. 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. 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. 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.
Measure Participants 6 6 6 6 6 6
Day 1
4.3778
(46.7)
7.0123
(14.4)
4.9815
(73.3)
6.4761
(47.1)
6.6860
(33.3)
7.0636
(46.9)
Day 9
4.7194
(34.2)
6.8928
(17.7)
4.8972
(34.5)
6.4278
(33.0)
6.2139
(34.1)
7.2237
(43.7)
25. Secondary Outcome
Title Terminal Disposition Phase Half-life for TAK-020 in Part 1 (SRD)
Description
Time Frame Pre-dose and multiple timepoints (up to 96 hours) post-dose in Part 1

Outcome Measure Data

Analysis Population Description
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.
Arm/Group Title Part 1 Cohort 1: TAK-020 0.1 mg Part 1 Cohort 2: TAK-020 0.5 mg Part 1 Cohort 3: TAK-020 2.5 mg Part 1 Cohort 4: TAK-020 4.4 mg Part 1 Cohort 5: TAK-020 8.8 mg Part 1 Cohort 6: TAK-020 17.5 mg Part 1 Cohort 7: TAK-020 35 mg Part 1 Cohort 8: TAK-020 70 mg Part 1 Cohort 9: TAK-020 105 mg
Arm/Group Description TAK-020 0.1 milligram (mg), solution, orally once on Day 1. TAK-020 0.5 mg, solution, orally, once on Day 1 following review of safety, tolerability and pharmacokinetic (PK) data from Cohort 1. TAK-020 2.5 mg, solution, orally once on Day 1 following review of safety, tolerability and PK data from Cohort 2. TAK-020 4.4 mg, solution, orally once on Day 1 following review of safety, tolerability and PK data from Cohort 3. TAK-020 8.8 mg, solution, orally once on Day 1 following review of safety, tolerability and PK data from Cohort 4. TAK-020 17.5 mg, solution, orally once on Day 1 following review of safety, tolerability and PK data from Cohort 5. 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. 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. 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.
Measure Participants 6 6 6 6 6 6 6 6 6
Mean (Standard Deviation) [hr]
1.1251
(0.16347)
1.5323
(0.28359)
2.2093
(0.41162)
3.0159
(0.70963)
4.8384
(1.06916)
4.2946
(1.18227)
6.0601
(1.55255)
6.1098
(1.65014)
9.0275
(4.78526)
26. Secondary Outcome
Title T1/2z : Terminal Disposition Phase Half-life (T1/2z) for TAK-020 in Part 2 (MRD)
Description
Time Frame 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

Outcome Measure Data

Analysis Population Description
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.
Arm/Group Title Part 2 Cohort 1: TAK-020 3.75 mg Part 2 Cohort 2: TAK-020 5.75 mg Part 2 Cohort 3: TAK-020 13 mg Part 2 Cohort 4: TAK-020 25 mg Part 2 Cohort 5: TAK-020 45 mg Part 2 Cohort 6: TAK-020 60 mg
Arm/Group Description 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. 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. 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. 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. 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. 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.
Measure Participants 6 6 6 6 6 6
Day 1
2.5948
(0.42162)
3.3397
(0.96341)
4.1895
(0.40518)
4.8507
(2.21078)
6.0124
(2.30297)
6.2971
(1.82711)
Day 9
2.1537
(0.42833)
3.2089
(0.77467)
4.1335
(0.51741)
3.7934
(0.70657)
5.1273
(1.58301)
5.4635
(1.47268)
27. Secondary Outcome
Title Lambda z (Λz): Terminal Disposition Phase Rate Constant for TAK-020 (SRD)
Description
Time Frame Pre-dose and multiple timepoints (up to 96 hours) post-dose in Part 1

Outcome Measure Data

Analysis Population Description
Pharmacokinetic set included all participants who received study drug and had at least one measurable plasma concentration or amount of drug in the urine.
Arm/Group Title Part 1 Cohort 1: TAK-020 0.1 mg Part 1 Cohort 2: TAK-020 0.5 mg Part 1 Cohort 3: TAK-020 2.5 mg Part 1 Cohort 4: TAK-020 4.4 mg Part 1 Cohort 5: TAK-020 8.8 mg Part 1 Cohort 6: TAK-020 17.5 mg Part 1 Cohort 7: TAK-020 35 mg Part 1 Cohort 8: TAK-020 70 mg Part 1 Cohort 9: TAK-020 105 mg
Arm/Group Description TAK-020 0.1 milligram (mg), solution, orally once on Day 1. TAK-020 0.5 mg, solution, orally, once on Day 1 following review of safety, tolerability and pharmacokinetic (PK) data from Cohort 1. TAK-020 2.5 mg, solution, orally once on Day 1 following review of safety, tolerability and PK data from Cohort 2. TAK-020 4.4 mg, solution, orally once on Day 1 following review of safety, tolerability and PK data from Cohort 3. TAK-020 8.8 mg, solution, orally once on Day 1 following review of safety, tolerability and PK data from Cohort 4. TAK-020 17.5 mg, solution, orally once on Day 1 following review of safety, tolerability and PK data from Cohort 5. 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. 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. 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.
Measure Participants 6 6 6 6 6 6 6 6 6
Mean (Standard Deviation) [1/hr]
0.6226
(0.09046)
0.4659
(0.08893)
0.3223
(0.05573)
0.2402
(0.05603)
0.1496
(0.03468)
0.1745
(0.05957)
0.1202
(0.02831)
0.1216
(0.03677)
0.1004
(0.06068)
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part 1 Cohort 1-9: Placebo, Part 1 Cohort 1: TAK-020 0.1 mg, Part 1 Cohort 2: TAK-020 0.5 mg, Part 1 Cohort 3: TAK-020 2.5 mg, Part 1 Cohort 4: TAK-020 4.4 mg, Part 1 Cohort 5: TAK-020 8.8 mg, Part 1 Cohort 6: TAK-020 17.5 mg, Part 1 Cohort 7: TAK-020 35 mg, Part 1 Cohort 8: TAK-020 70 mg
Comments
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value <.0001
Comments
Method ANOVA
Comments Statistical analysis results were obtained using ANOVA with dose level as a fixed effect.
28. Secondary Outcome
Title Lamda z (Λz):Terminal Disposition Phase Rate Constant for TAK-020 (MRD)
Description
Time Frame 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

Outcome Measure Data

Analysis Population Description
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.
Arm/Group Title Part 2 Cohort 1: TAK-020 3.75 mg Part 2 Cohort 2: TAK-020 5.75 mg Part 2 Cohort 3: TAK-020 13 mg Part 2 Cohort 4: TAK-020 25 mg Part 2 Cohort 5: TAK-020 45 mg Part 2 Cohort 6: TAK-020 60 mg
Arm/Group Description 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. 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. 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. 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. 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. 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.
Measure Participants 6 6 6 6 6 6
Day 1
0.2732
(0.04550)
0.2231
(0.06562)
0.1667
(0.01608)
0.1655
(0.05994)
0.1263
(0.03599)
0.1216
(0.04880)
Day 9
0.3325
(0.07185)
0.2264
(0.05325)
0.1699
(0.02117)
0.1880
(0.03581)
0.1471
(0.04752)
0.1363
(0.04310)
29. Secondary Outcome
Title Tlag: Lag Time to First Quantifiable Concentration for TAK-020 (SRD)
Description
Time Frame Pre-dose and multiple timepoints (up to 96 hours) post-dose in Part 1

Outcome Measure Data

Analysis Population Description
Pharmacokinetic set included all participants who received study drug and had at least one measurable plasma concentration or amount of drug in the urine.
Arm/Group Title Part 1 Cohort 1: TAK-020 0.1 mg Part 1 Cohort 2: TAK-020 0.5 mg Part 1 Cohort 3: TAK-020 2.5 mg Part 1 Cohort 4: TAK-020 4.4 mg Part 1 Cohort 5: TAK-020 8.8 mg Part 1 Cohort 6: TAK-020 17.5 mg Part 1 Cohort 7: TAK-020 35 mg Part 1 Cohort 8: TAK-020 70 mg Part 1 Cohort 9: TAK-020 105 mg
Arm/Group Description TAK-020 0.1 milligram (mg), solution, orally once on Day 1. TAK-020 0.5 mg, solution, orally, once on Day 1 following review of safety, tolerability and pharmacokinetic (PK) data from Cohort 1. TAK-020 2.5 mg, solution, orally once on Day 1 following review of safety, tolerability and PK data from Cohort 2. TAK-020 4.4 mg, solution, orally once on Day 1 following review of safety, tolerability and PK data from Cohort 3. TAK-020 8.8 mg, solution, orally once on Day 1 following review of safety, tolerability and PK data from Cohort 4. TAK-020 17.5 mg, solution, orally once on Day 1 following review of safety, tolerability and PK data from Cohort 5. 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. 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. 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.
Measure Participants 6 6 6 6 6 6 6 6 6
Median (Full Range) [hr]
0.0000
0.0000
0.0000
0.0000
0.0000
0.0000
0.0000
0.0000
0.0000
30. Secondary Outcome
Title Tlag: Lag Time to First Quantifiable Concentration for TAK-020 (MRD)
Description
Time Frame 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

Outcome Measure Data

Analysis Population Description
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.
Arm/Group Title Part 2 Cohort 1: TAK-020 3.75 mg Part 2 Cohort 2: TAK-020 5.75 mg Part 2 Cohort 3: TAK-020 13 mg Part 2 Cohort 4: TAK-020 25 mg Part 2 Cohort 5: TAK-020 45 mg Part 2 Cohort 6: TAK-020 60 mg
Arm/Group Description 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. 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. 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. 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. 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. 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.
Measure Participants 6 6 6 6 6 6
Day 1
0.0000
0.0000
0.0000
0.0000
0.0000
0.0000
Day 9
0.0000
0.0000
0.0000
0.0000
0.0000
0.0000
31. Secondary Outcome
Title CL/F: Apparent Clearance After Extravascular Administration Calculated Using the Observed Value of the Last Quantifiable Concentration of TAK-020 in Part 1 (SRD)
Description CL/F was calculated as dose/AUC∞.
Time Frame Pre-dose and multiple timepoints (up to 96 hours) post-dose in Part 1

Outcome Measure Data

Analysis Population Description
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.
Arm/Group Title Part 1 Cohort 1: TAK-020 0.1 mg Part 1 Cohort 2: TAK-020 0.5 mg Part 1 Cohort 3: TAK-020 2.5 mg Part 1 Cohort 4: TAK-020 4.4 mg Part 1 Cohort 5: TAK-020 8.8 mg Part 1 Cohort 6: TAK-020 17.5 mg Part 1 Cohort 7: TAK-020 35 mg Part 1 Cohort 8: TAK-020 70 mg Part 1 Cohort 9: TAK-020 105 mg
Arm/Group Description TAK-020 0.1 milligram (mg), solution, orally once on Day 1. TAK-020 0.5 mg, solution, orally, once on Day 1 following review of safety, tolerability and pharmacokinetic (PK) data from Cohort 1. TAK-020 2.5 mg, solution, orally once on Day 1 following review of safety, tolerability and PK data from Cohort 2. TAK-020 4.4 mg, solution, orally once on Day 1 following review of safety, tolerability and PK data from Cohort 3. TAK-020 8.8 mg, solution, orally once on Day 1 following review of safety, tolerability and PK data from Cohort 4. TAK-020 17.5 mg, solution, orally once on Day 1 following review of safety, tolerability and PK data from Cohort 5. 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. 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. 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.
Measure Participants 6 6 6 6 6 6 6 6 6
Mean (Standard Deviation) [L/h]
74.6058
(22.96089)
134.3327
(36.96594)
90.8722
(42.30328)
64.9449
(15.91608)
92.1842
(34.02451)
67.4975
(25.25161)
96.6058
(32.53095)
70.7695
(22.35098)
116.6389
(16.07341)
32. Secondary Outcome
Title CL/F: Apparent Clearance After Extravascular Administration Calculated Using the Observed Value of the Last Quantifiable Concentration of TAK-020 in Part 2 (MRD)
Description CL/F was calculated as dose/AUCτ.
Time Frame 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

Outcome Measure Data

Analysis Population Description
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.
Arm/Group Title Part 2 Cohort 1: TAK-020 3.75 mg Part 2 Cohort 2: TAK-020 5.75 mg Part 2 Cohort 3: TAK-020 13 mg Part 2 Cohort 4: TAK-020 25 mg Part 2 Cohort 5: TAK-020 45 mg Part 2 Cohort 6: TAK-020 60 mg
Arm/Group Description 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. 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. 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. 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. 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. 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.
Measure Participants 6 6 6 6 6 6
Day 1
118.3171
(58.62331)
67.1355
(11.81065)
100.6915
(62.33954)
68.2909
(29.74598)
79.5377
(22.34558)
76.9650
(28.27771)
Day 9
103.2882
(42.85829)
58.3884
(12.20159)
96.5521
(46.88638)
64.1696
(16.00068)
71.1027
(16.99648)
64.2873
(29.63651)
33. Secondary Outcome
Title 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)
Description Vz/F was calculated as (CL/F)/λz.
Time Frame Pre-dose and multiple timepoints (up to 96 hours) post-dose in Part 1

Outcome Measure Data

Analysis Population Description
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.
Arm/Group Title Part 1 Cohort 1: TAK-020 0.1 mg Part 1 Cohort 2: TAK-020 0.5 mg Part 1 Cohort 3: TAK-020 2.5 mg Part 1 Cohort 4: TAK-020 4.4 mg Part 1 Cohort 5: TAK-020 8.8 mg Part 1 Cohort 6: TAK-020 17.5 mg Part 1 Cohort 7: TAK-020 35 mg Part 1 Cohort 8: TAK-020 70 mg Part 1 Cohort 9: TAK-020 105 mg
Arm/Group Description TAK-020 0.1 milligram (mg), solution, orally once on Day 1. TAK-020 0.5 mg, solution, orally, once on Day 1 following review of safety, tolerability and pharmacokinetic (PK) data from Cohort 1. TAK-020 2.5 mg, solution, orally once on Day 1 following review of safety, tolerability and PK data from Cohort 2. TAK-020 4.4 mg, solution, orally once on Day 1 following review of safety, tolerability and PK data from Cohort 3. TAK-020 8.8 mg, solution, orally once on Day 1 following review of safety, tolerability and PK data from Cohort 4. TAK-020 17.5 mg, solution, orally once on Day 1 following review of safety, tolerability and PK data from Cohort 5. 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. 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. 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.
Measure Participants 6 6 6 6 6 6 6 6 6
Mean (Standard Deviation) [L]
118.3923
(19.67518)
292.2714
(78.43782)
290.5190
(160.50093)
281.7423
(101.64610)
655.4794
(320.11459)
416.8746
(183.79449)
807.4773
(200.14983)
594.3399
(149.97225)
1573.1600
(901.24407)
34. Secondary Outcome
Title 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)
Description Vz/F was calculated as (CL/F)/λz.
Time Frame 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

Outcome Measure Data

Analysis Population Description
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.
Arm/Group Title Part 2 Cohort 1: TAK-020 3.75 mg Part 2 Cohort 2: TAK-020 5.75 mg Part 2 Cohort 3: TAK-020 13 mg Part 2 Cohort 4: TAK-020 25 mg Part 2 Cohort 5: TAK-020 45 mg Part 2 Cohort 6: TAK-020 60 mg
Arm/Group Description 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. 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. 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. 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. 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. 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.
Measure Participants 6 6 6 6 6 6
Day 1
442.5900
(248.99792)
329.6057
(135.47030)
632.4288
(438.98268)
460.7824
(218.14865)
698.3679
(373.79793)
715.0788
(414.96986)
Day 9
366.8037
(178.07012)
266.5672
(68.21454)
565.3577
(252.08686)
352.4564
(114.45822)
530.4696
(211.00235)
503.3324
(298.76176)
35. Secondary Outcome
Title Ae(0-24) : Amount of Drug Excreted in Urine During a 24-hour Dosing Interval for TAK-020 in Part 1 (SRD)
Description 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.
Time Frame Pre-dose and multiple timepoints (up to 24 hours) post-dose in Part 1

Outcome Measure Data

Analysis Population Description
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.
Arm/Group Title Part 1 Cohort 1: TAK-020 0.1 mg Part 1 Cohort 2: TAK-020 0.5 mg Part 1 Cohort 3: TAK-020 2.5 mg Part 1 Cohort 4: TAK-020 4.4 mg Part 1 Cohort 5: TAK-020 8.8 mg Part 1 Cohort 6: TAK-020 17.5 mg Part 1 Cohort 7: TAK-020 35 mg Part 1 Cohort 8: TAK-020 70 mg Part 1 Cohort 9: TAK-020 105 mg
Arm/Group Description TAK-020 0.1 milligram (mg), solution, orally once on Day 1. TAK-020 0.5 mg, solution, orally, once on Day 1 following review of safety, tolerability and pharmacokinetic (PK) data from Cohort 1. TAK-020 2.5 mg, solution, orally once on Day 1 following review of safety, tolerability and PK data from Cohort 2. TAK-020 4.4 mg, solution, orally once on Day 1 following review of safety, tolerability and PK data from Cohort 3. TAK-020 8.8 mg, solution, orally once on Day 1 following review of safety, tolerability and PK data from Cohort 4. TAK-020 17.5 mg, solution, orally once on Day 1 following review of safety, tolerability and PK data from Cohort 5. 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. 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. 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.
Measure Participants 6 6 6 6 6 6 6 6 6
Mean (Standard Deviation) [mg]
0.002473
(0.0008033)
0.009898
(0.0049671)
0.069183
(0.0289653)
0.128195
(0.0412071)
0.227985
(0.0762743)
0.507260
(0.1109721)
0.963253
(0.3108451)
2.010763
(0.3615714)
1.925176
(0.6269670)
36. Secondary Outcome
Title Ae(0-24): Amount of Drug Excreted in Urine During a 24-hour Dosing Interval for TAK-020 in Part 2 (MRD)
Description 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.
Time Frame Pre-dose and multiple timepoints (up to 24 hours) post-dose on Day 1 and Day 9 in Part 2

Outcome Measure Data

Analysis Population Description
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.
Arm/Group Title Part 2 Cohort 1: TAK-020 3.75 mg Part 2 Cohort 2: TAK-020 5.75 mg Part 2 Cohort 3: TAK-020 13 mg Part 2 Cohort 4: TAK-020 25 mg Part 2 Cohort 5: TAK-020 45 mg Part 2 Cohort 6: TAK-020 60 mg
Arm/Group Description 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. 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. 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. 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. 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. 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.
Measure Participants 6 6 6 6 6 6
Day 1
0.086153
(0.0362135)
0.149595
(0.0378613)
0.418761
(0.1666534)
1.095832
(0.4029873)
1.186754
(0.3087747)
1.569498
(0.3542760)
Day 9
0.089955
(0.0423540)
0.181305
(0.0555997)
0.385163
(0.1034764)
1.004047
(0.2138181)
1.370011
(0.3414174)
2.165337
(0.3525765)
37. Secondary Outcome
Title Ae(0-96): Amount of Drug Excreted in Urine From Time 0 to Time 96 Hours for TAK-020 in Part 1 (SRD)
Description
Time Frame Pre-dose and multiple timepoints (up to 96 hours) post-dose in Part 1

Outcome Measure Data

Analysis Population Description
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.
Arm/Group Title Part 1 Cohort 1: TAK-020 0.1 mg Part 1 Cohort 2: TAK-020 0.5 mg Part 1 Cohort 3: TAK-020 2.5 mg Part 1 Cohort 4: TAK-020 4.4 mg Part 1 Cohort 5: TAK-020 8.8 mg Part 1 Cohort 6: TAK-020 17.5 mg Part 1 Cohort 7: TAK-020 35 mg Part 1 Cohort 8: TAK-020 70 mg Part 1 Cohort 9: TAK-020 105 mg
Arm/Group Description TAK-020 0.1 milligram (mg), solution, orally once on Day 1. TAK-020 0.5 mg, solution, orally, once on Day 1 following review of safety, tolerability and pharmacokinetic (PK) data from Cohort 1. TAK-020 2.5 mg, solution, orally once on Day 1 following review of safety, tolerability and PK data from Cohort 2. TAK-020 4.4 mg, solution, orally once on Day 1 following review of safety, tolerability and PK data from Cohort 3. TAK-020 8.8 mg, solution, orally once on Day 1 following review of safety, tolerability and PK data from Cohort 4. TAK-020 17.5 mg, solution, orally once on Day 1 following review of safety, tolerability and PK data from Cohort 5. 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. 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. 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.
Measure Participants 6 6 6 6 6 6 6 6 6
Mean (Standard Deviation) [mg]
0.002473
(0.0008033)
0.009999
(0.0049464)
0.069676
(0.0288376)
0.128604
(0.0411008)
0.229946
(0.0763608)
0.514036
(0.1144776)
0.977421
(0.3148372)
2.062580
(0.3829068)
1.988120
(0.6152605)
38. Secondary Outcome
Title Fe(0-24): Fraction of Drug Excreted in Urine for TAK-020 in Part 1 (SRD)
Description Fe was calculated as (Aet/dose)*100.
Time Frame Pre-dose and multiple timepoints (up to 24 hours) post-dose in Part 1

Outcome Measure Data

Analysis Population Description
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.
Arm/Group Title Part 1 Cohort 1: TAK-020 0.1 mg Part 1 Cohort 2: TAK-020 0.5 mg Part 1 Cohort 3: TAK-020 2.5 mg Part 1 Cohort 4: TAK-020 4.4 mg Part 1 Cohort 5: TAK-020 8.8 mg Part 1 Cohort 6: TAK-020 17.5 mg Part 1 Cohort 7: TAK-020 35 mg Part 1 Cohort 8: TAK-020 70 mg Part 1 Cohort 9: TAK-020 105 mg
Arm/Group Description TAK-020 0.1 milligram (mg), solution, orally once on Day 1. TAK-020 0.5 mg, solution, orally, once on Day 1 following review of safety, tolerability and pharmacokinetic (PK) data from Cohort 1. TAK-020 2.5 mg, solution, orally once on Day 1 following review of safety, tolerability and PK data from Cohort 2. TAK-020 4.4 mg, solution, orally once on Day 1 following review of safety, tolerability and PK data from Cohort 3. TAK-020 8.8 mg, solution, orally once on Day 1 following review of safety, tolerability and PK data from Cohort 4. TAK-020 17.5 mg, solution, orally once on Day 1 following review of safety, tolerability and PK data from Cohort 5. 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. 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. 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.
Measure Participants 6 6 6 6 6 6 6 6 6
Mean (Standard Deviation) [percentage of TAK-020 dose]
2.4733
(0.80334)
1.9796
(0.99341)
2.7673
(1.15861)
2.9135
(0.93653)
2.5907
(0.86675)
2.8986
(0.63413)
2.7522
(0.88813)
2.8725
(0.51653)
1.8335
(0.59711)
39. Secondary Outcome
Title Fe(0-24): Fraction of Drug Excreted in Urine for TAK-020 in Part 2 (MRD)
Description Fe was calculated as (Aet/dose)*100.
Time Frame Pre-dose and multiple timepoints (up to 24 hours) post-dose on Day 1 and Day 9 in Part 2

Outcome Measure Data

Analysis Population Description
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.
Arm/Group Title Part 2 Cohort 1: TAK-020 3.75 mg Part 2 Cohort 2: TAK-020 5.75 mg Part 2 Cohort 3: TAK-020 13 mg Part 2 Cohort 4: TAK-020 25 mg Part 2 Cohort 5: TAK-020 45 mg Part 2 Cohort 6: TAK-020 60 mg
Arm/Group Description 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. 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. 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. 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. 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. 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.
Measure Participants 6 6 6 6 6 6
Day 1
2.2974
(0.96569)
2.6016
(0.65846)
3.2212
(1.28195)
4.3833
(1.61195)
2.6372
(0.68617)
2.6158
(0.59046)
Day 9
2.3988
(1.12944)
3.1531
(0.96695)
2.9628
(0.79597)
4.0162
(0.85527)
3.0445
(0.75871)
3.6089
(0.58763)
40. Secondary Outcome
Title Fe(0-96): Fraction of Drug Excreted in Urine for TAK-020 in Part 1 (SRD)
Description Fe was calculated as (Aet/dose)*100.
Time Frame Pre-dose and multiple timepoints (up to 96 hours) post-dose in Part 1

Outcome Measure Data

Analysis Population Description
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.
Arm/Group Title Part 1 Cohort 1: TAK-020 0.1 mg Part 1 Cohort 2: TAK-020 0.5 mg Part 1 Cohort 3: TAK-020 2.5 mg Part 1 Cohort 4: TAK-020 4.4 mg Part 1 Cohort 5: TAK-020 8.8 mg Part 1 Cohort 6: TAK-020 17.5 mg Part 1 Cohort 7: TAK-020 35 mg Part 1 Cohort 8: TAK-020 70 mg Part 1 Cohort 9: TAK-020 105 mg
Arm/Group Description TAK-020 0.1 milligram (mg), solution, orally once on Day 1. TAK-020 0.5 mg, solution, orally, once on Day 1 following review of safety, tolerability and pharmacokinetic (PK) data from Cohort 1. TAK-020 2.5 mg, solution, orally once on Day 1 following review of safety, tolerability and PK data from Cohort 2. TAK-020 4.4 mg, solution, orally once on Day 1 following review of safety, tolerability and PK data from Cohort 3. TAK-020 8.8 mg, solution, orally once on Day 1 following review of safety, tolerability and PK data from Cohort 4. TAK-020 17.5 mg, solution, orally once on Day 1 following review of safety, tolerability and PK data from Cohort 5. 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. 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. 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.
Measure Participants 6 6 6 6 6 6 6 6 6
Mean (Standard Deviation) [percentage of TAK-020 dose]
2.4733
(0.80334)
1.9999
(0.98928)
2.7870
(1.15351)
2.9228
(0.93411)
2.6130
(0.86774)
2.9373
(0.65416)
2.7926
(0.89953)
2.9465
(0.54701)
1.8934
(0.58596)
41. Secondary Outcome
Title Renal Clearance (CLr) for TAK-020 in Part 1 (SRD)
Description CLr was calculated as (Ae96/AUCt)*100.
Time Frame Pre-dose and multiple timepoints (up to 96 hours) post-dose in Part 1

Outcome Measure Data

Analysis Population Description
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.
Arm/Group Title Part 1 Cohort 1: TAK-020 0.1 mg Part 1 Cohort 2: TAK-020 0.5 mg Part 1 Cohort 3: TAK-020 2.5 mg Part 1 Cohort 4: TAK-020 4.4 mg Part 1 Cohort 5: TAK-020 8.8 mg Part 1 Cohort 6: TAK-020 17.5 mg Part 1 Cohort 7: TAK-020 35 mg Part 1 Cohort 8: TAK-020 70 mg Part 1 Cohort 9: TAK-020 105 mg
Arm/Group Description TAK-020 0.1 milligram (mg), solution, orally once on Day 1. TAK-020 0.5 mg, solution, orally, once on Day 1 following review of safety, tolerability and pharmacokinetic (PK) data from Cohort 1. TAK-020 2.5 mg, solution, orally once on Day 1 following review of safety, tolerability and PK data from Cohort 2. TAK-020 4.4 mg, solution, orally once on Day 1 following review of safety, tolerability and PK data from Cohort 3. TAK-020 8.8 mg, solution, orally once on Day 1 following review of safety, tolerability and PK data from Cohort 4. TAK-020 17.5 mg, solution, orally once on Day 1 following review of safety, tolerability and PK data from Cohort 5. 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. 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. 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.
Measure Participants 6 6 6 6 6 6 6 6 6
Mean (Standard Deviation) [L/h]
3.6856
(1.20477)
2.6010
(0.62075)
2.5250
(1.30987)
2.0190
(0.47688)
2.2159
(0.15331)
1.8896
(0.60426)
2.6108
(1.03807)
2.0007
(0.28823)
2.1898
(0.63728)
42. Secondary Outcome
Title Renal Clearance (CLr) for TAK-020 in Part 2 (MRD)
Description CLr was calculated as (Ae24/AUC24)*100.
Time Frame 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

Outcome Measure Data

Analysis Population Description
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.
Arm/Group Title Part 2 Cohort 1: TAK-020 3.75 mg Part 2 Cohort 2: TAK-020 5.75 mg Part 2 Cohort 3: TAK-020 13 mg Part 2 Cohort 4: TAK-020 25 mg Part 2 Cohort 5: TAK-020 45 mg Part 2 Cohort 6: TAK-020 60 mg
Arm/Group Description 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. 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. 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. 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. 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. 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.
Measure Participants 6 6 6 6 6 6
Day 1
2.3165
(0.35669)
1.7168
(0.42806)
2.8969
(1.50559)
2.6497
(0.42235)
2.1525
(0.83694)
1.9597
(0.52835)
Day 9
2.0802
(0.36760)
1.7732
(0.41318)
2.6754
(1.08869)
2.5311
(0.65737)
2.2053
(0.80067)
2.2405
(0.82268)
43. Secondary Outcome
Title R: Linearity Index Calculated as AUC24 at Steady State/AUC∞ After a Single Dose for TAK-020 in Part 2 (MRD)
Description
Time Frame 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

Outcome Measure Data

Analysis Population Description
Pharmacokinetic set included all participants who received study drug and had at least one measurable plasma concentration or amount of drug in the urine.
Arm/Group Title Part 2 Cohort 1: TAK-020 3.75 mg Part 2 Cohort 2: TAK-020 5.75 mg Part 2 Cohort 3: TAK-020 13 mg Part 2 Cohort 4: TAK-020 25 mg Part 2 Cohort 5: TAK-020 45 mg Part 2 Cohort 6: TAK-020 60 mg
Arm/Group Description 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. 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. 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. 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. 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. 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.
Measure Participants 6 6 6 6 6 6
Day 1
3.551
(0.1578)
4.463
(0.1578)
5.010
(0.1578)
5.940
(0.1728)
6.376
(0.1578)
6.716
(0.1578)
Day 9
3.665
(0.1578)
4.608
(0.1578)
4.992
(0.1578)
5.993
(0.1728)
6.475
(0.1578)
6.919
(0.1578)
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part 1 Cohort 1-9: Placebo
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Estimated Ratio
Estimated Value 1.121
Confidence Interval (2-Sided) 90%
0.772 to 1.628
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Part 1 Cohort 1: TAK-020 0.1 mg
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Estimated Ratio
Estimated Value 1.156
Confidence Interval (2-Sided) 90%
0.796 to 1.678
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Part 1 Cohort 2: TAK-020 0.5 mg
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Estimated Ratio
Estimated Value 0.982
Confidence Interval (2-Sided) 90%
0.676 to 1.425
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Part 1 Cohort 3: TAK-020 2.5 mg
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Estimated Ratio
Estimated Value 1.055
Confidence Interval (2-Sided) 90%
0.701 to 1.587
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Part 1 Cohort 4: TAK-020 4.4 mg
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Estimated Ratio
Estimated Value 1.105
Confidence Interval (2-Sided) 90%
0.761 to 1.604
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Part 1 Cohort 5: TAK-020 8.8 mg
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Estimated Ratio
Estimated Value 1.225
Confidence Interval (2-Sided) 90%
0.844 to 1.778
Parameter Dispersion Type:
Value:
Estimation Comments

Adverse Events

Time Frame 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)
Adverse Event Reporting Description At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Arm/Group Title Part 1 Cohort 1-9: Placebo Part 1 Cohort 1: TAK-020 0.1 mg Part 1 Cohort 2: TAK-020 0.5 mg Part 1 Cohort 3: TAK-020 2.5 mg Part 1 Cohort 4: TAK-020 4.4 mg Part 1 Cohort 5: TAK-020 8.8 mg Part 1 Cohort 6: TAK-020 17.5 mg Part 1 Cohort 7: TAK-020 35 mg Part 1 Cohort 8: TAK-020 70 mg Part 1 Cohort 9: TAK-020 105 mg Part 2 Cohort 1-6: Placebo Part 2 Cohort 1: TAK-020 3.75 mg Part 2 Cohort 2: TAK-020 5.75 mg Part 2 Cohort 3: TAK-020 13 mg Part 2 Cohort 4: TAK-020 25 mg Part 2 Cohort 5: TAK-020 45 mg Part 2 Cohort 6: TAK-020 60 mg
Arm/Group Description TAK-020 placebo-matching solution, orally, once on Day 1. TAK-020 0.1 milligram (mg), solution, orally once on Day 1. TAK-020 0.5 mg, solution, orally, once on Day 1 following review of safety, tolerability and pharmacokinetic (PK) data from Cohort 1. TAK-020 2.5 mg, solution, orally once on Day 1 following review of safety, tolerability and PK data from Cohort 2. TAK-020 4.4 mg, solution, orally once on Day 1 following review of safety, tolerability and PK data from Cohort 3. TAK-020 8.8 mg, solution, orally once on Day 1 following review of safety, tolerability and PK data from Cohort 4. TAK-020 17.5 mg, solution, orally once on Day 1 following review of safety, tolerability and PK data from Cohort 5. 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. 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. 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. TAK-020 placebo-matching solution, orally, once on Day 1 and Days 3 to 9. 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. 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. 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. 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. 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. 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.
All Cause Mortality
Part 1 Cohort 1-9: Placebo Part 1 Cohort 1: TAK-020 0.1 mg Part 1 Cohort 2: TAK-020 0.5 mg Part 1 Cohort 3: TAK-020 2.5 mg Part 1 Cohort 4: TAK-020 4.4 mg Part 1 Cohort 5: TAK-020 8.8 mg Part 1 Cohort 6: TAK-020 17.5 mg Part 1 Cohort 7: TAK-020 35 mg Part 1 Cohort 8: TAK-020 70 mg Part 1 Cohort 9: TAK-020 105 mg Part 2 Cohort 1-6: Placebo Part 2 Cohort 1: TAK-020 3.75 mg Part 2 Cohort 2: TAK-020 5.75 mg Part 2 Cohort 3: TAK-020 13 mg Part 2 Cohort 4: TAK-020 25 mg Part 2 Cohort 5: TAK-020 45 mg Part 2 Cohort 6: TAK-020 60 mg
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 0/18 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/12 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%)
Serious Adverse Events
Part 1 Cohort 1-9: Placebo Part 1 Cohort 1: TAK-020 0.1 mg Part 1 Cohort 2: TAK-020 0.5 mg Part 1 Cohort 3: TAK-020 2.5 mg Part 1 Cohort 4: TAK-020 4.4 mg Part 1 Cohort 5: TAK-020 8.8 mg Part 1 Cohort 6: TAK-020 17.5 mg Part 1 Cohort 7: TAK-020 35 mg Part 1 Cohort 8: TAK-020 70 mg Part 1 Cohort 9: TAK-020 105 mg Part 2 Cohort 1-6: Placebo Part 2 Cohort 1: TAK-020 3.75 mg Part 2 Cohort 2: TAK-020 5.75 mg Part 2 Cohort 3: TAK-020 13 mg Part 2 Cohort 4: TAK-020 25 mg Part 2 Cohort 5: TAK-020 45 mg Part 2 Cohort 6: TAK-020 60 mg
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 0/18 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/12 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%)
Other (Not Including Serious) Adverse Events
Part 1 Cohort 1-9: Placebo Part 1 Cohort 1: TAK-020 0.1 mg Part 1 Cohort 2: TAK-020 0.5 mg Part 1 Cohort 3: TAK-020 2.5 mg Part 1 Cohort 4: TAK-020 4.4 mg Part 1 Cohort 5: TAK-020 8.8 mg Part 1 Cohort 6: TAK-020 17.5 mg Part 1 Cohort 7: TAK-020 35 mg Part 1 Cohort 8: TAK-020 70 mg Part 1 Cohort 9: TAK-020 105 mg Part 2 Cohort 1-6: Placebo Part 2 Cohort 1: TAK-020 3.75 mg Part 2 Cohort 2: TAK-020 5.75 mg Part 2 Cohort 3: TAK-020 13 mg Part 2 Cohort 4: TAK-020 25 mg Part 2 Cohort 5: TAK-020 45 mg Part 2 Cohort 6: TAK-020 60 mg
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 2/18 (11.1%) 0/6 (0%) 0/6 (0%) 1/6 (16.7%) 0/6 (0%) 1/6 (16.7%) 0/6 (0%) 0/6 (0%) 3/6 (50%) 1/6 (16.7%) 5/12 (41.7%) 1/6 (16.7%) 3/6 (50%) 3/6 (50%) 2/6 (33.3%) 1/6 (16.7%) 1/6 (16.7%)
Gastrointestinal disorders
Abdominal distension 0/18 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 1/6 (16.7%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/12 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%)
Abdominal pain upper 0/18 (0%) 0/6 (0%) 0/6 (0%) 1/6 (16.7%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/12 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%)
Nausea 0/18 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 1/6 (16.7%) 0/6 (0%) 1/12 (8.3%) 1/6 (16.7%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%)
Diarrhoea 0/18 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/12 (0%) 1/6 (16.7%) 1/6 (16.7%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%)
Lip dry 0/18 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/12 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 1/6 (16.7%) 0/6 (0%) 0/6 (0%)
General disorders
Axillary pain 0/18 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/12 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 1/6 (16.7%) 0/6 (0%)
Infections and infestations
Upper respiratory tract infection 0/18 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 2/12 (16.7%) 0/6 (0%) 0/6 (0%) 1/6 (16.7%) 0/6 (0%) 0/6 (0%) 1/6 (16.7%)
Metabolism and nutrition disorders
Decreased appetite 0/18 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 1/6 (16.7%) 0/6 (0%) 0/12 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%)
Musculoskeletal and connective tissue disorders
Musculoskeletal discomfort 0/18 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/12 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 1/6 (16.7%)
Nervous system disorders
Headache 1/18 (5.6%) 0/6 (0%) 0/6 (0%) 1/6 (16.7%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 3/12 (25%) 0/6 (0%) 2/6 (33.3%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%)
Dizziness 1/18 (5.6%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 2/12 (16.7%) 0/6 (0%) 0/6 (0%) 1/6 (16.7%) 0/6 (0%) 1/6 (16.7%) 0/6 (0%)
Hypoaesthesia 0/18 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/12 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 1/6 (16.7%) 0/6 (0%)
Somnolence 0/18 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/12 (0%) 0/6 (0%) 0/6 (0%) 1/6 (16.7%) 0/6 (0%) 0/6 (0%) 0/6 (0%)
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain 1/18 (5.6%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/12 (0%) 0/6 (0%) 2/6 (33.3%) 1/6 (16.7%) 0/6 (0%) 0/6 (0%) 0/6 (0%)
Cough 0/18 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 2/12 (16.7%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 1/6 (16.7%) 0/6 (0%) 0/6 (0%)
Nasal congestion 0/18 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 1/12 (8.3%) 0/6 (0%) 1/6 (16.7%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%)
Rhinorrhoea 0/18 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/12 (0%) 0/6 (0%) 1/6 (16.7%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%)
Sinus congestion 0/18 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/12 (0%) 0/6 (0%) 1/6 (16.7%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%)
Throat irritation 0/18 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/12 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 1/6 (16.7%) 0/6 (0%) 0/6 (0%)
Skin and subcutaneous tissue disorders
Ecchymosis 1/18 (5.6%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/12 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%)
Pruritus 0/18 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/12 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 1/6 (16.7%) 0/6 (0%)
Vascular disorders
Phlebitis 0/18 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 1/6 (16.7%) 0/12 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%)
Phlebitis superficial 0/18 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 1/6 (16.7%) 0/6 (0%) 0/12 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Research Organization shall not publish any articles or papers nor make any presentations, nor assist any other person in publishing any articles or papers or in making any presentations relating or referring to the Study or any results, data or insights from or any data, information or materials obtained or generated in the performance of its obligations without the prior written consent of Takeda, which consent may be granted or withheld in Takeda's sole discretion.

Results Point of Contact

Name/Title Medical Director
Organization Takeda
Phone +1-877-825-3327
Email trialdisclosures@takeda.com
Responsible Party:
Takeda
ClinicalTrials.gov Identifier:
NCT02413255
Other Study ID Numbers:
  • TAK-020-1001
  • U1111-1163-9637
First Posted:
Apr 9, 2015
Last Update Posted:
Jan 7, 2019
Last Verified:
Jun 1, 2018