Study of TAK-071 in Healthy Participants and Participants With Mild Cognitive Impairment/Mild Alzheimer Disease and Relative Bioavailability (BA) and Food Effect of TAK-071 in Healthy Participants

Sponsor
Takeda (Industry)
Overall Status
Terminated
CT.gov ID
NCT02769065
Collaborator
(none)
179
1
30
13.1
13.7

Study Details

Study Description

Brief Summary

The purpose of this study was to assess the safety, tolerability, and pharmacokinetic (PK) of TAK-071 when administered as single rising dose (SRD) and multiple rising dose (MRD) orally in healthy participants and participants with mild cognitive impairment (MCI) or mild Alzheimer disease (AD).

Condition or Disease Intervention/Treatment Phase
Phase 1

Detailed Description

TAK-071 was being tested to find a safe and well-tolerated dose in healthy participants (non-Japanese and Japanese) and participants with MCI or mild AD (non-Japanese).

The study enrolled 179 participants. The study consisted of 4 parts: Single-rising dose (SRD) part (Cohorts 1-6, and 18-22), multiple-rising dose (MRD) part (Cohorts 7-15), Cohort 16 with 2-arm parallel design, and Cohort 17 relative bioavailability and food effect 3 period crossover design.

Participants in each cohort were randomized to receive treatment with TAK-071 or matching placebo using drug-in-capsule (DIC) in the morning following a minimum fast of 8 hours. In Cohort 16, participants were assigned to 1 of 2 possible treatments, TAK-071 or matching placebo. In Cohort 17, participants were assigned to 1 of 3 treatment sequences (ABC, BCA, or CAB) with treatment A being fasted state and capsule formulation, treatment B being fasted state and tablet formulation, and treatment C being fed state and tablet formulation. In Cohorts 20-22, participants were administered as a single dose of TAK-071 or placebo on Day 1, and a single dose of donepezil or placebo approximately 24 hours later on Day 2.

This multi-center trial was conducted in United States. The overall time to participate in this study was approximately 41 days. Participants made multiple visits to the clinic and were also contacted for the follow-up through the telephone.

Study Design

Study Type:
Interventional
Actual Enrollment :
179 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
A Phase 1 Safety, Tolerability, and Pharmacokinetic Study of Escalating Single and Multiple Oral Doses of TAK-071 in Healthy Subjects and Subjects With Mild Cognitive Impairment/Mild Alzheimer Disease and Relative Bioavailability and Food Effect of TAK-071 in Healthy Subjects
Actual Study Start Date :
May 5, 2016
Actual Primary Completion Date :
Jun 8, 2017
Actual Study Completion Date :
Jun 8, 2017

Arms and Interventions

Arm Intervention/Treatment
Placebo Comparator: SRD: Placebo Cohorts 1-6, 18 and 19

TAK-071 placebo-matching capsules, orally, once on Day 1 to non-Japanese healthy participants in the single-rising dose (SRD) period.

Drug: TAK-071 Placebo
TAK-071 placebo-matching capsules

Experimental: SRD: Cohort 1: TAK-071 1 mg

TAK-071 1 mg, capsule, orally, once on Day 1 to non-Japanese healthy participants.

Drug: TAK-071
TAK-071 capsules

Experimental: SRD: Cohort 2: TAK-071 3 mg

TAK-071 3 mg capsule, orally, once on Day 1 to non-Japanese healthy participants. Dose of TAK-071 was based on the 24-hour post-dose safety, tolerability and pharmacokinetic (PK) data from cohort 1.

Drug: TAK-071
TAK-071 capsules

Experimental: SRD: Cohort 3: TAK-071 9 mg

TAK-071 9 mg capsule, orally, once on Day 1 to non-Japanese healthy participants. Dose of TAK-071 was based on 24-hour safety, tolerability, and preliminary plasma PK and 12-hour CSF PK data.

Drug: TAK-071
TAK-071 capsules

Experimental: SRD: Cohort 4: TAK-071 20 mg

TAK-071 20 mg capsule, orally, once on Day 1 to non-Japanese healthy participants. Dose of TAK-071 was based on the 24-hour post-dose safety and tolerability data from previous cohort.

Drug: TAK-071
TAK-071 capsules

Experimental: SRD: Cohort 5: TAK-071 40 mg

TAK-071 40 mg capsule, orally, once on Day 1 to non-Japanese healthy participants. Dose of TAK-071 will be based on 24-hour safety, tolerability, and preliminary plasma PK data from Cohort 4.

Drug: TAK-071
TAK-071 capsules

Experimental: SRD: Cohort 6: TAK-071 80 mg

TAK-071 80 mg capsules, orally, once on Day 1 to non-Japanese healthy participants. Dose of TAK-071 was based on 24-hour safety, tolerability, and preliminary plasma PK data from Cohort 5

Drug: TAK-071
TAK-071 capsules

Placebo Comparator: MRD: Placebo Cohorts 7-9

TAK-071 placebo-matching capsule, orally, once on Day 1 to non-Japanese healthy participants in the multiple-rising dose (MRD) period.

Drug: TAK-071 Placebo
TAK-071 placebo-matching capsules

Experimental: MRD: Cohort 7: TAK-071 3 mg

TAK-071 3 mg capsules, orally, once daily from Day 1 up to Day 21 to non-Japanese healthy participants. Dose of TAK-071 was based on 24-hour safety and tolerability from Cohort 4 and the 24-hour preliminary plasma PK and 12-hour CSF PK data from Cohort 3.

Drug: TAK-071
TAK-071 capsules

Experimental: MRD: Cohort 8: TAK-071 9 mg

TAK-071 9 mg capsules, orally, once daily from Day 1 up to Day 21 to non-Japanese healthy participants. Dose of TAK-071 was based on safety, tolerability and available PK data arising from the ongoing SRD part and previous MRD cohort.

Drug: TAK-071
TAK-071 capsules

Experimental: MRD: Cohort 9: TAK-071 15 mg

TAK-071 15 mg capsule, orally, once on Day 1, followed by a washout period of 7 days, then TAK-071 once daily for 21 days to non-Japanese healthy participants. Dose of TAK-071 will be based on safety, tolerability and available PK data arising from the ongoing SRD part and previous MRD cohort.

Drug: TAK-071
TAK-071 capsules

Placebo Comparator: MRD: TAK-071 Placebo Cohorts 10-12+Donepezil

TAK-071 placebo-matching capsule, orally, once daily along with donepezil 5 mg, tablets, orally, once daily from Day 1 up to Day 21 to non-Japanese healthy participants who were pre-treated with donepezil 5 mg, tablet, once daily for 3 weeks prior to administration of TAK-071.

Drug: Donepezil
Donepezil over-encapsulated tablet

Drug: TAK-071 Placebo
TAK-071 placebo-matching capsules

Experimental: MRD: Cohort 10: TAK-071 3 mg+Donepezil 5 mg

TAK-071 3 mg capsules, orally, once daily along with donepezil 5 mg, tablets, orally, once daily from Day 1 up to Day 21 to non-Japanese healthy participants who were pre-treated with donepezil 5 mg, tablet, once daily for 3 weeks prior to administration of TAK-071. Dose of TAK-071 was same as the dose used in MRD Cohort 7.

Drug: TAK-071
TAK-071 capsules

Drug: Donepezil
Donepezil over-encapsulated tablet

Experimental: MRD: Cohort 11: TAK-071 9 mg + Donepezil 5 mg

TAK-071 9 mg capsules, orally, once daily along with donepezil 5 mg, tablets, orally, once daily from Day 1 up to Day 21 to non-Japanese healthy participants who were pre-treated with donepezil 5 mg, tablet, once daily for 3 weeks prior to administration of TAK-071. Dose of TAK-071 was same as the dose used in MRD Cohort 8.

Drug: TAK-071
TAK-071 capsules

Drug: Donepezil
Donepezil over-encapsulated tablet

Experimental: MRD: Cohort 12: TAK-071 15 mg+Donepezil 5 mg

TAK-071 15 mg capsule, orally, once daily along with donepezil 5 mg, tablets, orally, once daily from Day 1 up to Day 21 to non-Japanese healthy participants who were pre-treated with donepezil 5 mg, tablet, once daily for 3 weeks prior to administration of TAK-071. Dose of TAK-071 was same as the dose used in MRD Cohort 9.

Drug: TAK-071
TAK-071 capsules

Drug: Donepezil
Donepezil over-encapsulated tablet

Experimental: MRD: Placebo Cohorts 13-15

TAK-071 placebo-matching capsule, orally, once on Day 1 to Japanese healthy participants.

Drug: TAK-071 Placebo
TAK-071 placebo-matching capsules

Experimental: MRD: Cohort 13: TAK-071 3 mg

TAK-071 3 mg capsule, orally, once on Day 1, followed by a washout period of 7 days, then TAK-071 once daily for 21 days to Japanese healthy participants. Dose of TAK-071 was same as the dose used in MRD Cohort 7.

Drug: TAK-071
TAK-071 capsules

Experimental: MRD: Cohort 14: TAK-071 9 mg

TAK-071 9 mg capsule or matching placebo, orally, once on Day 1, followed by a washout period of 7 days, then TAK-071 once daily for 21 days to Japanese healthy participants. Dose of TAK-071 was same as the dose used in MRD Cohort 8.

Drug: TAK-071
TAK-071 capsules

Experimental: MRD: Cohort 15: TAK-071 15 mg

TAK-071 15 mg capsule, orally, once on Day 1, followed by a washout period of 7 days, then TAK-071 once daily for 21 days to Japanese healthy participants. Dose of TAK-071 was same as the dose used in MRD Cohort 9.

Drug: TAK-071
TAK-071 capsules

Experimental: Cohort 16

Drug: TAK-071
TAK-071 capsules

Experimental: Bioavailability (BA)/Food Effect: Cohort 17 Sequence ABC

A: TAK-071 10 mg capsule, orally once on Day 1 in the fasted state in Period 1, followed by B: TAK-071 10 mg tablet, orally, once on Day 1 in the fasted state in Period 2, followed by C: TAK-071 10 mg tablet, orally, once on Day 1 in the fed state in Period 3 in non-Japanese healthy participants. There was a 21-day washout after each period.

Drug: TAK-071
TAK-071 capsules

Experimental: BA/Food Effect: Cohort 17 Sequence BCA

B: TAK-071 10 mg tablet, orally, once on Day 1 in the fasted state in Period 1, followed by C: TAK-071 10 mg tablet, orally, once on Day 1 in the Fed state in Period 2, followed by A: TAK-071 10 mg capsule, orally once on Day 1 in the fasted state Period 3 in non-Japanese healthy participants. There was a 21-day washout after each period.

Drug: TAK-071
TAK-071 capsules

Experimental: BA/Food Effect: Cohort 17 Sequence CAB

C: TAK-071 10 mg tablet, orally, once on Day 1 in the fed state in Period 1, followed by A: TAK-071 10 mg capsule, orally once on Day 1 in the fasted state in Period 2, followed by B: TAK-20 10 mg tablet, orally, once on Day 1 in the fasted state in Period 3 in non-Japanese healthy participants. There was a 21-day washout after each period.

Drug: TAK-071
TAK-071 capsules

Experimental: SRD: Cohort 18: TAK-071 120 mg

TAK-071 120 mg capsule, orally, once on Day 1 to non-Japanese healthy participants. Dose of TAK-071 was based on 24-hour safety, tolerability, and preliminary plasma PK data from Cohort 6.

Drug: TAK-071
TAK-071 capsules

Experimental: SRD: Cohort 19: TAK-071 160 mg

TAK-071 160 mg capsule, orally, once on Day 1 to non-Japanese healthy participants. Dose of TAK-071 was based on 24-hour safety, tolerability, and preliminary plasma PK data from Cohort 18.

Drug: TAK-071
TAK-071 capsules

Placebo Comparator: SRD: TAK-071 Placebo+Donepezil Placebo

TAK-071 placebo-matching capsule, orally, once on Day 1 followed by donepezil placebo-matching tablet, orally on Day 2 to non-Japanese healthy participants.

Drug: TAK-071 Placebo
TAK-071 placebo-matching capsules

Drug: Donepezil Placebo
Donepezil placebo-matching over-encapsulated tablet

Placebo Comparator: SRD: TAK-071 Placebo+Donepezil

TAK-071 placebo-matching capsule, orally, once on Day 1 followed by donepezil 10 mg tablet, orally, on Day 2 to non-Japanese healthy participants.

Drug: Donepezil
Donepezil over-encapsulated tablet

Drug: TAK-071 Placebo
TAK-071 placebo-matching capsules

Experimental: SRD: Cohort 20: TAK-071 40 mg+Donepezil

TAK-071 40 mg capsule, orally, once on Day 1 followed by donepezil 10 mg, tablets, orally, once on Day 2 to non-Japanese healthy participants. Dose of TAK-071 was based on 24-hour safety, tolerability, and preliminary plasma PK data from Cohort 19.

Drug: TAK-071
TAK-071 capsules

Drug: Donepezil
Donepezil over-encapsulated tablet

Experimental: SRD: Cohort 21: TAK-071 60 mg+Donepezil

TAK-071 60 mg capsule, orally, once on Day 1 followed by donepezil 10 mg, tablets, orally, once on Day 2 to non-Japanese healthy participants. Dose of TAK-071 was based on 24-hour safety and tolerability data from Cohort 20.

Drug: TAK-071
TAK-071 capsules

Drug: Donepezil
Donepezil over-encapsulated tablet

Experimental: SRD: Cohort 22: TAK-071 80 mg+Donepizil

TAK-071 80 mg capsule, orally, once on Day 1, followed by donepezil 10 mg, tablets, orally, once on Day 2 to non-Japanese healthy participants. Dose of TAK-071 was based on 24-hour safety and tolerability data from Cohort 21.

Drug: TAK-071
TAK-071 capsules

Drug: Donepezil
Donepezil over-encapsulated tablet

Outcome Measures

Primary Outcome Measures

  1. Percentage of Participants Who Experienced at Least One Treatment-Emergent Adverse Event (TEAE) [Day 1 up to Day 41]

    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 with an onset that occurs or gets worse after receiving study drug.

  2. Percentage of Participants Who Meet the Markedly Abnormal Criteria for Clinical Laboratory Tests at Least Once Post-dose [Day 1 up to Day 41]

    Clinical laboratory tests included serum chemistry, hematology, coagulation and urinalysis. ULN=upper limit of normal range.

  3. Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose [Day 1 up to Day 41]

    Vital Sign measurements included systolic blood pressure (SBP), diastolic blood presssure (DBP), pulse, temperature, orthostatic SBP, orthostatic DBP and orthostatic pulse.

  4. Percentage of Participants Who Meet the Markedly Abnormal Criteria for 12-lead Electrocardiogram (ECG) Parameters at Least Once Post-dose [Day 1 up to Day 41]

    A standard 12-lead electrocardiogram (ECG) was performed. The percentage of participants with markedly abnormal ECG findings during the study.

  5. Tmax: Time of First Occurrence of Cmax for TAK-071 Single-Rising Dose (SRD) Non-Japanese Participants [Pre-dose on Day 1 and at multiple time points (up to 168 hours) post-dose]

  6. Tmax: Time of First Occurrence of Cmax for TAK-071 Multiple-Rising Dose (MRD) Non-Japanese Participants [Day 1] [Pre-dose on Day 1 and multiple time points (up to 24 hours) post-dose]

  7. Tmax: Time of First Occurrence of Cmax for TAK-071 MRD Non-Japanese Participants [Day 21] [Pre-dose on Day 21 and multiple time points (up to 24 hours) post-dose]

  8. Tmax: Time of First Occurrence of Cmax for TAK-071 MRD Non-Japanese Participants [Day 1] [Pre-dose on Day 1 and multiple time points (up to 96 hours) post-dose]

  9. Tmax: Time of First Occurrence of Cmax for TAK-071 MRD Non-Japanese Participants [Day 8] [Pre-dose on Day 8 and multiple time points (up to 24 hour) post-dose]

  10. Tmax: Time of First Occurrence of Cmax for TAK-071 MRD Non-Japanese Participants [Day 28] [Pre-dose on Day 28 and multiple time points (up to 36 hours) post-dose]

  11. Tmax: Time of First Occurrence of Cmax for TAK-071 MRD Japanese Participants [Day 1] [Pre-dose on Day 1 and multiple time points (up to 96 hours) post-dose]

  12. Tmax: Time of First Occurrence of Cmax for TAK-071 MRD Japanese Participants [Day 8] [Pre-dose on Day 8 and multiple time points (up to 24 hours) post-dose]

  13. Tmax: Time of First Occurrence of Cmax for TAK-071 MRD Japanese Participants [Day 28] [Pre-dose on Day 28 and multiple time points (up to 24 hours) post-dose]

  14. Tmax: Time of First Occurrence of Cmax for TAK-071 MRD Non-Japanese Participants [Day 1] [Pre-dose on Day 1 and multiple time points (up to 24 hours) post-dose]

  15. Tmax: Time of First Occurrence of Cmax for TAK-071 Relative Bioavailability and Food Effect [Pre-dose on Day 21 and multiple time points (up to 168 hours) post-dose]

  16. Tmax: Time of First Occurrence of Cmax for TAK-071 SRD Non-Japanese Participants TAK-071+Donepezil [Pre-dose on Day 1 and at multiple time points (up to 168 hours) post-dose]

  17. Cmax: Maximum Observed Plasma Concentration for TAK-071 Single-Rising Dose (SRD) Non-Japanese Participants [Pre-dose on Day 1 and at multiple time points (up to 168 hours) post-dose]

  18. Cmax: Maximum Observed Plasma Concentration for TAK-071 Multiple-Rising Dose (MRD) Non-Japanese Participants [Day 1] [Pre-dose on Day 1 and multiple time points (up to 24 hours) post-dose]

  19. Cmax: Maximum Observed Plasma Concentration for TAK-071 MRD Non-Japanese Participants [Day 21] [Pre-dose on Day 21 and multiple time points (up to 24 hours) post-dose]

  20. Cmax: Maximum Observed Plasma Concentration for TAK-071 MRD Non-Japanese Participants [Day 1] [Pre-dose on Day 1 and multiple time points (up to 96 hours) post-dose]

  21. Cmax: Maximum Observed Plasma Concentration for TAK-071 MRD Non-Japanese Participants [Day 8] [Pre-dose on Day 8 and multiple time points (up to 24 hour) post-dose]

  22. Cmax: Maximum Observed Plasma Concentration for TAK-071 MRD Non-Japanese Participants [Day 28] [Pre-dose on Day 28 and multiple time points (up to 36 hours) post-dose]

  23. Cmax: Maximum Observed Plasma Concentration for TAK-071 MRD Japanese Participants [Day 1] [Pre-dose on Day 1 and multiple time points (up to 96 hours) post-dose]

  24. Cmax: Maximum Observed Plasma Concentration for TAK-071 MRD Japanese Participants [Day 8] [Pre-dose on Day 8 and multiple time points (up to 24 hours) post-dose]

  25. Cmax: Maximum Observed Plasma Concentration for TAK-071 MRD Japanese Participants [Day 28] [Pre-dose on Day 28 and multiple time points (up to 24 hours) post-dose]

  26. Cmax: Maximum Observed Plasma Concentration for TAK-071 MRD Non-Japanese Participants [Day 1] [Pre-dose on Day 1 and multiple time points (up to 24 hours) post-dose]

  27. Cmax: Maximum Observed Plasma Concentration for TAK-071 Relative Bioavailability and Food Effect [Pre-dose on Day 1 and multiple time points (up to 168 hours) post-dose]

  28. Cmax: Maximum Observed Plasma Concentration for TAK-071 SRD Non-Japanese Participants TAK-071+Donepezil [Pre-dose on Day 1 and at multiple time points (up to 168 hours) post-dose]

  29. AUC(0-24): Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours for TAK-071 Single-Rising Dose (SRD) Non-Japanese Participants [Pre-dose on Day 1 and at multiple time points (up to 168 hours) post-dose]

  30. AUC(0-24): Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours for TAK-071 Multiple-Rising Dose (MRD) Non-Japanese Participants [Day 1] [Pre-dose on Day 1 and multiple time points (up to 24 hours) post-dose]

  31. AUC(0-24): Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours for TAK-071 MRD Non-Japanese Participants [Day 21] [Pre-dose on Day 21 and multiple time points (up to 24 hours) post-dose]

  32. AUC(0-24): Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours for TAK-071 MRD Non-Japanese Participants [Day 1] [Pre-dose on Day 1 and multiple time points (up to 96 hours) post-dose]

  33. AUC(0-24): Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours for TAK-071 MRD Non-Japanese Participants [Day 8] [Pre-dose on Day 8 and multiple time points (up to 24 hour) post-dose]

  34. AUC(0-24): Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours for TAK-071 MRD Non-Japanese Participants [Day 28] [Pre-dose on Day 28 and multiple time points (up to 36 hours) post-dose]

  35. AUC(0-24): Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours for TAK-071 MRD Japanese Participants [Day 1] [Pre-dose on Day 1 and multiple time points (up to 96 hours) post-dose]

  36. AUC(0-24): Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours for TAK-071 MRD Japanese Participants [Day 8] [Pre-dose on Day 8 and multiple time points (up to 24 hours) post-dose]

  37. AUC(0-24): Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours for TAK-071 MRD Japanese Participants [Day 28] [Pre-dose on Day 28 and multiple time points (up to 24 hours) post-dose]

  38. AUC(0-24): Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours for TAK-071 MRD Non-Japanese Participants [Day 1] [Pre-dose on Day 1 and multiple time points (up to 24 hours) post-dose]

  39. AUC∞: Area Under the Plasma Concentration-Time Curve From Time 0 to Infinity for TAK-071 Relative Bioavailability and Food Effect [Pre-dose on Day 21 and multiple time points (up to 168 hours) post-dose]

  40. AUC(0-24): Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours for TAK-071 SRD Non-Japanese Participants TAK-071+Donepezil [Pre-dose on Day 1 and at multiple time points (up to 168 hours) post-dose]

  41. AUC∞: Area Under the Concentration-Time Curve From Time 0 to Infinity, Calculated Using the Observed Value of the Last Quantifiable Concentration for TAK-071 SRD Non-Japanese Participants [Pre-dose on Day 1 and at multiple time points [up to 168 hours] post-dose]

  42. AUC∞: Area Under the Concentration-Time Curve From Time 0 to Infinity, Calculated Using the Observed Value of the Last Quantifiable Concentration for TAK-071 SRD Non-Japanese Participants TAK-071 + Donepezil [Pre-dose on Day 1 and at multiple time points [up to 168 hours] post-dose]

Secondary Outcome Measures

  1. AUClast: Area Under the Concentration-time Curve From Time 0 to Time of the Last Quantifiable Concentration for TAK-071 MRD Non-Japanese Participants [Pre-dose on Day 1 and at multiple time points (up to 168 hours) post-dose]

  2. AUClast: Area Under the Concentration-time Curve From Time 0 to Time of the Last Quantifiable Concentration for TAK-071 MRD Non-Japanese Participants [Pre-dose on Day 1 and multiple timepoints (up to 24 hrs) post-dose for Cohorts 7 and 8 and Pre-dose on Day 1 and multiple timepoints (up to 96 hrs) post-dose for Cohort 9]

  3. AUClast: Area Under the Concentration-time Curve From Time 0 to Time of the Last Quantifiable Concentration for TAK-071 MRD Japanese Participants [Pre-dose on Day 1 and multiple time points (up to 96 hours) post-dose and Pre-dose on Day 8 and multiple time points (up to 24 hours) post-dose]

  4. AUClast: Area Under the Concentration-time Curve From Time 0 to Time of the Last Quantifiable Concentration for TAK-071 MRD Non-Japanese [Pre-dose on Day 1 and at multiple time points (up to 24 hours) post-dose]

  5. AUClast: Area Under the Concentration-time Curve From Time 0 to Time of the Last Quantifiable Concentration for TAK-071 Relative Bioavailability and Food Effect [Pre-dose on Day 1 and multiple time points (up to 168 hours) post-dose]

  6. AUClast: Area Under the Concentration-time Curve From Time 0 to Time of the Last Quantifiable Concentration for TAK-071 SRD Non-Japanese Participants TAK-071+Donepezil [Pre-dose on Day 1 and multiple time points (up to 168 hours) post-dose]

  7. Terminal Disposition Phase Half-life (t1/2z) for TAK-071 SRD Non-Japanese Participants [Pre-dose on Day 1 and at multiple time points (up to 168 hours) post-dose]

  8. Terminal Disposition Phase Half-life (t1/2z) for TAK-071 Relative Bioavailability and Food Effect [Pre-dose on Day 21 and multiple time points (up to 168 hours) post-dose]

  9. Terminal Disposition Phase Half-life (t1/2z) for TAK-071 SRD Non-Japanese Participants TAK-071+Donepezil [Pre-dose on Day 1 and multiple time points (up to 168 hours) post-dose]

  10. CL/F: Apparent Clearance After Extravascular Administration for TAK-071 SRD Non-Japanese Participants [Pre-dose on Day 1 and at multiple time points (up to 168 hours) post-dose]

  11. CL/F: Apparent Clearance After Extravascular Administration for TAK-071 Relative Bioavailability and Food Effect [Pre-dose on Day 21 and multiple time points (up to 168 hours) post-dose]

  12. CL/F: Apparent Clearance After Extravascular Administration for TAK-071 SRD Non-Japanese Participants TAK-071+Donepezil [Pre-dose on Day 1 and at multiple time points (up to 168 hours) post-dose]

  13. Vz/F: Apparent Volume of Distribution During the Terminal Disposition Phase After Extravascular Administration for TAK-071 SRD Non-Japanese Participants [Pre-dose on Day 1 and at multiple time points (up to 168 hours) post-dose]

  14. Vz/F: Apparent Volume of Distribution During the Terminal Disposition Phase After Extravascular Administration for TAK-071 Relative Bioavailability and Food Effect [Pre-dose on Day 21 and multiple time points (up to 168 hours) post-dose]

  15. Vz/F: Apparent Volume of Distribution During the Terminal Disposition Phase After Extravascular Administration for TAK-071 SRD Non-Japanese Participants TAK-071 + Donepezil [Pre-dose on Day 1 and at multiple time points (up to 168 hours) post-dose]

  16. Accumulation Ratio Based on AUCτ (Rac[AUC]) for TAK-071 MRD Non-Japanese Participants [Pre-dose on Day 21 and at multiple time points (up to 24 hours) post-dose for Cohorts 7 and 8 and Pre-dose on Day 28 and at multiple time points (up to 36 hours) post-dose for Cohort 9]

  17. Accumulation Ratio Based on AUCτ (Rac[AUC]) for TAK-071 MRD Japanese Participants [Pre-dose on Day 28 and at multiple time points [up to 24 hours] post-dose]

  18. Accumulation Ratio Based on AUCτ (Rac[AUC]) for TAK-071 MRD Non-Japanese Participants [Pre-dose on Day 21 and at multiple time points [up to 24 hours] post-dose]

  19. Accumulation Ratio Based on Plasma Cmax (Rac[Cmax]) for TAK-071 MRD Non-Japanese Participants [Pre-dose on Day 21 and at multiple time points [up to 24 hours] post-dose for Cohorts 7 and 8 and Pre-dose on Day 28 and at multiple time points (up to 36 hours) post-dose for Cohort 9]

  20. Accumulation Ratio Based on Plasma Cmax (Rac[Cmax]) for TAK-071 MRD Japanese Participants [Pre-dose on Day 28 and at multiple time points [up to 24 hours] post-dose]

  21. Accumulation Ratio Based on Plasma Cmax (Rac[Cmax]) for TAK-071 MRD Non-Japanese Participants [Pre-dose on Day 21 and at multiple time points [up to 24 hours] post-dose]

  22. AEt: Amount of Drug Excreted in Urine From Time 0 to Time t for TAK-071 SRD Non-Japanese Participants [Pre-dose on Day 1 and at multiple time points [up to 96 hours] post-dose]

  23. AEt: Amount of Drug Excreted in Urine From Time 0 to Time t for TAK-071 MRD Non-Japanese Participants [Pre-dose on Day 1 and 21 and at multiple time points (up to 24 hours) post-dose for Cohorts 7 and 8, and pre-dose on Day 1 and 28 and multiple time points (up to 96 hours) post-dose for Cohort 9]

  24. AEt: Amount of Drug Excreted in Urine From Time 0 to Time t for TAK-071 MRD Japanese Participants [Pre-dose on Day 1 and at multiple time points (up to 96 hours) post-dose and pre-dose on Day 28 and multiple time points (up to 24 hours) post-dose]

  25. Fet: Fraction of Administered Dose of Drug Excreted in Urine From Time 0 to Time t for TAK-071 SRD Non-Japanese Participants [Pre-dose on Day 1 and at multiple time points (up to 96 hours) post-dose]

  26. Fet: Fraction of Administered Dose of Drug Excreted in Urine From Time 0 to Time t for TAK-071 MRD Non-Japanese Participants [Pre-dose on Days 1 and 21 and at multiple time points (up to 24 hours) post-dose for Cohorts 7 and 8 and Pre-dose on Days 1 and 28 and multiple time points (up to 96 hours) post-dose for Cohort 9]

  27. Fet: Fraction of Administered Dose of Drug Excreted in Urine From Time 0 to Time t for TAK-071 MRD Japanese Participants [Pre-dose on Day 1 and at multiple time points (up to 96 hours) post-dose and pre-dose on Day 28 and multiple time points (up to 24 hours) post-dose]

  28. CLR: Renal Clearance for TAK-071 SRD Non-Japanese Participants [Pre-dose on Day 1 and at multiple time points [up to 96 hours] post-dose]

  29. CLR: Renal Clearance for TAK-071 MRD Non-Japanese Participants [Pre-dose on Days 1 and 21 and at multiple time points (up to 24 hours) post-dose for Cohorts 7 and 8 and Pre-dose on Days 1 and 28 multiple time points (up to 96 hours) post-dose for Cohort 9]

  30. CLR: Renal Clearance for TAK-071 MRD Japanese Participants [Pre-dose on Day 1 and at multiple time points (up to 96 hours) post-dose and pre-dose on Day 28 and multiple time points (up to 24 hours) post-dose]

  31. CSF Cmax: Maximum Observed Concentration in Cerebrospinal Fluid (CSF) for TAK-071 [Pre-dose on Day 1 and at multiple time points (up to 12 hours) post-dose]

  32. CSF Cmax: Maximum Observed Concentration in Cerebrospinal Fluid (CSF) for TAK-071 [Pre-dose on Day 28 and at multiple time points (up to 36 hours) post-dose]

  33. CSF AUC(0-12): Area Under the CSF Concentration-time Curve From Time 0 to 12 Hours for TAK-071 [Pre-dose on Day 1 and at multiple time points (up to 12 hours) post-dose]

  34. CSF AUC(0-36): Area Under the CSF Concentration-time Curve From Time 0 to 36 Hours for TAK-071 [Pre-dose on Day 28 and multiple time points (up to 36 hours) post-dose]

  35. Ratio of CSF AUC(0-12) to the Plasma AUC(0-12) for TAK-071 [Pre-dose on Day 1 and at multiple time points [up to 168 hours] post-dose]

  36. Ratio of CSF AUC(0-36) to the Plasma AUC(0-36) for TAK-071 [Pre-dose on Day 28 and multiple time points (up to 36 hours) post-dose Cohort 9]

  37. Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Donepezil MRD Non-Japanese Participants [Pre-dose on Days -1 and 21 and multiple time points (up to 24 hours) post-dose]

  38. Cmax: Maximum Observed Plasma Concentration for Donepezil MRD Non-Japanese Participants [Pre-dose on Days -1 and 21 and multiple time points (up to 24 hours) post-dose]

  39. AUC(0-24): Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours Post-dose for Donepezil [Pre-dose on Days -1 and 21 and multiple time points (up to 24 hours) post-dose]

  40. Ratio of Geometric Mean of Cmax for Donepezil After 21 Daily Doses of TAK-071 [Pre-dose on Days -1 and 21 and multiple time points (up to 24 hours) post-dose]

    A linear mixed effect model on the natural log-transformed parameters was performed with day as a fixed effect and participant as a random effect. Ratio is the exponentiated geometric mean value Day 21/Day -1 on the original scale.

  41. Ratio of Geometric Mean of AUC(0-24) for Donepezil After 21 Daily Doses of TAK-071 [Pre-dose on Days -1 and 21 and multiple time points (up to 24 hours) post-dose]

    A linear mixed effect model on the natural log-transformed parameters was performed with day as a fixed effect and participant as a random effect. Ratio is the exponentiated geometric mean value Day 21/Day -1 on the original scale.

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years to 90 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
Yes
Inclusion Criteria:
  1. Man or woman who weighs at least 50 kg and has a body mass index (BMI) from 18.0 to 30.0 kg/m^2, inclusive, at Screening. Participants should be aged 18 to 55 years, inclusive (nonelderly at the time of informed consent and first study drug dose) for Cohorts 1 to 12, and 17 to 22; 20 to 55 years, inclusive, for Cohorts 13 to 15; and 55 to 90 years, inclusive, for participants in Cohort 16.

  2. For Cohorts 13 to 15 only: First-generation Japanese, defined as having been born in Japan of Japanese parents and Japanese grandparents and living no more than 10 years outside of Japan, with no significant change in lifestyle, including diet, while living outside of Japan.

  3. Cohort 16 only: Healthy elderly or participants with MCI or mild AD, who must have Mini Mental State Examination (MMSE) score of 18 to 30, inclusive or 18 to 26 inclusive, respectively, and no biomarker data to contradict this diagnosis. Participants with documented diagnosis of MCI or mild AD must be receiving ongoing donepezil therapy (10 mg) in the evening for a minimum of 21 days prior to Check-in (Day -1) or must consent to take donepezil dose titrated to at least 21 days of treatment with 10 mg QD prior to Check-in.

Exclusion Criteria:
  1. Has clinically significant (Cohorts 1 to 15 and 17 to 22) or uncontrolled (Cohort 16) neurologic, cardiovascular, pulmonary, hepatic, renal, metabolic, gastrointestinal (GI), urologic, immunologic, endocrine, or psychiatric disease or other abnormality (other than the disease being studied), which may impact the ability of the participant to participate or potentially confound the study results.

  2. Has a history of type 1 diabetes (Cohorts 1 to 22) or type 2 diabetes (Cohorts 1 to 15, 17 to 22) or hemoglobin A1c >6.5% at Screening. Note: participants with controlled (hemoglobin A1c <7.0% at Screening) type 2 diabetes in Cohort 16 may participate in the study.

  3. Has a risk of suicide or suicidal ideation with intent and plan according to the investigator's clinical judgment (affirmative answer to questions 4 and 5 of the ideation section of the Columbia-Suicide Severity Rating Scale) or has made a suicide attempt in the previous 6 months.

  4. Cohort 16 only: Any significant neurologic disease (other than suspected incipient or mild AD), such as Parkinson disease, stroke, transient ischemic attack, multi-infarct dementia, Huntington disease, head trauma with clinically significant cognitive sequelae, or chronic central nervous system infection, per investigator discretion.

  5. Has current or recent (within 6 months) GI disease that would be expected to influence the absorption of drugs (ie, a history of malabsorption, any surgical intervention known to impact absorption [eg, bariatric surgery or bowel resection], esophageal reflux, peptic ulcer disease, erosive esophagitis, or frequent [more than once per week] occurrence of heartburn).

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:
NCT02769065
Other Study ID Numbers:
  • TAK-071-1001
  • U1111-1176-7435
First Posted:
May 11, 2016
Last Update Posted:
Jun 10, 2019
Last Verified:
Mar 1, 2019
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by Takeda
Additional relevant MeSH terms:

Study Results

Participant Flow

Recruitment Details Participants took part in the study at 1 investigative site in United States from 05 May 2016 to 08 June 2017.
Pre-assignment Detail Healthy participants (non-Japanese and Japanese) and participants with mild cognitive impairment (MCI) or mild Alzheimer disease (AD) (non-Japanese) were enrolled in cohorts: TAK-071 single-rising-dose (SRD), multiple-rising dose (MRD), Food Effect Crossover or in combination with donepezil.
Arm/Group Title SRD: Placebo Cohorts 1-6, 18 and 19 SRD: Cohort 1: TAK-071 1 mg SRD: Cohort 2: TAK-071 3 mg SRD: Cohort 3: TAK-071 9 mg SRD: Cohort 4: TAK-071 20 mg SRD: Cohort 5: TAK-071 40 mg SRD: Cohort 6: TAK-071 80 mg MRD: Placebo Cohorts 7-9 MRD: Cohort 7: TAK-071 3 mg MRD: Cohort 8: TAK-071 9 mg MRD: Cohort 9: TAK-071 15 mg MRD: TAK-071 Placebo Cohorts 10-12+Donepezil MRD: Cohort 10: TAK-071 3 mg+Donepezil 5 mg MRD: Cohort 11: TAK-071 9 mg + Donepezil 5 mg MRD: Cohort 12: TAK-071 15 mg+Donepezil 5 mg MRD: Placebo Cohorts 13-15 MRD: Cohort 13: TAK-071 3 mg MRD: Cohort 14: TAK-071 9 mg MRD: Cohort 15: TAK-071 15 mg Cohort 16 Bioavailability (BA)/Food Effect: Cohort 17 Sequence ABC BA/Food Effect: Cohort 17 Sequence BCA BA/Food Effect: Cohort 17 Sequence CAB SRD: Cohort 18: TAK-071 120 mg SRD: Cohort 19: TAK-071 160 mg SRD: TAK-071 Placebo+Donepezil Placebo SRD: TAK-071 Placebo+Donepezil SRD: Cohort 20: TAK-071 40 mg+Donepezil SRD: Cohort 21: TAK-071 60 mg+Donepezil SRD: Cohort 22: TAK-071 80 mg+Donepezil
Arm/Group Description TAK-071 placebo-matching capsules, orally, once on Day 1 to non-Japanese healthy participants in the single-rising dose (SRD) period. TAK-071 1 mg, capsule, orally, once on Day 1 to non-Japanese healthy participants. TAK-071 3 mg capsule, orally, once on Day 1 to non-Japanese healthy participants. Dose of TAK-071 was based on the 24-hour post-dose safety, tolerability and pharmacokinetic (PK) data from cohort 1. TAK-071 9 mg capsule, orally, once on Day 1 to non-Japanese healthy participants. Dose of TAK-071 was based on 24-hour safety, tolerability, and preliminary plasma PK and 12-hour CSF PK data. TAK-071 20 mg capsule, orally, once on Day 1 to non-Japanese healthy participants. Dose of TAK-071 was based on the 24-hour post-dose safety and tolerability data from previous cohort. TAK-071 40 mg capsule, orally, once on Day 1 to non-Japanese healthy participants. Dose of TAK-071 will be based on 24-hour safety, tolerability, and preliminary plasma PK data from Cohort 4. TAK-071 80 mg capsules, orally, once on Day 1 to non-Japanese healthy participants. Dose of TAK-071 was based on 24-hour safety, tolerability, and preliminary plasma PK data from Cohort 5 TAK-071 placebo-matching capsule, orally, once on Day 1 to non-Japanese healthy participants in the multiple-rising dose (MRD) period. TAK-071 3 mg capsules, orally, once daily from Day 1 up to Day 21 to non-Japanese healthy participants. Dose of TAK-071 was based on 24-hour safety and tolerability from Cohort 4 and the 24-hour preliminary plasma PK and 12-hour CSF PK data from Cohort 3. TAK-071 9 mg capsules, orally, once daily from Day 1 up to Day 21 to non-Japanese healthy participants. Dose of TAK-071 was based on safety, tolerability and available PK data arising from the ongoing SRD part and previous MRD cohort. TAK-071 15 mg capsule, orally, once on Day 1, followed by a washout period of 7 days, then TAK-071 once daily for 21 days to non-Japanese healthy participants. Dose of TAK-071 will be based on safety, tolerability and available PK data arising from the ongoing SRD part and previous MRD cohort. TAK-071 placebo-matching capsule, orally, once daily along with donepezil 5 mg, tablets, orally, once daily from Day 1 up to Day 21 to non-Japanese healthy participants who were pre-treated with donepezil 5 mg, tablet, once daily for 3 weeks prior to administration of TAK-071. TAK-071 3 mg capsules, orally, once daily along with donepezil 5 mg, tablets, orally, once daily from Day 1 up to Day 21 to non-Japanese healthy participants who were pre-treated with donepezil 5 mg, tablet, once daily for 3 weeks prior to administration of TAK-071. Dose of TAK-071 was same as the dose used in MRD Cohort 7. TAK-071 9 mg capsules, orally, once daily along with donepezil 5 mg, tablets, orally, once daily from Day 1 up to Day 21 to non-Japanese healthy participants who were pre-treated with donepezil 5 mg, tablet, once daily for 3 weeks prior to administration of TAK-071. Dose of TAK-071 was same as the dose used in MRD Cohort 8. TAK-071 15 mg capsule, orally, once daily along with donepezil 5 mg, tablets, orally, once daily from Day 1 up to Day 21 to non-Japanese healthy participants who were pre-treated with donepezil 5 mg, tablet, once daily for 3 weeks prior to administration of TAK-071. Dose of TAK-071 was same as the dose used in MRD Cohort 9. TAK-071 placebo-matching capsule, orally, once on Day 1 to Japanese healthy participants. TAK-071 3 mg capsule, orally, once on Day 1, followed by a washout period of 7 days, then TAK-071 once daily for 21 days to Japanese healthy participants. Dose of TAK-071 was same as the dose used in MRD Cohort 7. TAK-071 9 mg capsule or matching placebo, orally, once on Day 1, followed by a washout period of 7 days, then TAK-071 once daily for 21 days to Japanese healthy participants. Dose of TAK-071 was same as the dose used in MRD Cohort 8. TAK-071 15 mg capsule, orally, once on Day 1, followed by a washout period of 7 days, then TAK-071 once daily for 21 days to Japanese healthy participants. Dose of TAK-071 was same as the dose used in MRD Cohort 9. TAK-071 capsule, orally, once on Day 1 for 21 days, followed by a washout period of 21 days, or placebo matching tablets, orally, once on Day 1 for 21 days. Donepezil was delivered as 5 mg tablet, orally, once followed by 10 mg tablet, orally, once in run-in period. A: TAK-071 10 mg capsule, orally once on Day 1 in the fasted state in Period 1, followed by B: TAK-071 10 mg tablet, orally, once on Day 1 in the fasted state in Period 2, followed by C: TAK-071 10 mg tablet, orally, once on Day 1 in the fed state in Period 3 in non-Japanese healthy participants. There was a 21-day washout after each period. B: TAK-071 10 mg tablet, orally, once on Day 1 in the fasted state in Period 1, followed by C: TAK-071 10 mg tablet, orally, once on Day 1 in the Fed state in Period 2, followed by A: TAK-071 10 mg capsule, orally once on Day 1 in the fasted state Period 3 in non-Japanese healthy participants. There was a 21-day washout after each period. C: TAK-071 10 mg tablet, orally, once on Day 1 in the fed state in Period 1, followed by A: TAK-071 10 mg capsule, orally once on Day 1 in the fasted state in Period 2, followed by B: TAK-20 10 mg tablet, orally, once on Day 1 in the fasted state in Period 3 in non-Japanese healthy participants. There was a 21-day washout after each period. TAK-071 120 mg capsule, orally, once on Day 1 to non-Japanese healthy participants. Dose of TAK-071 was based on 24-hour safety, tolerability, and preliminary plasma PK data from Cohort 6. TAK-071 160 mg capsule, orally, once on Day 1 to non-Japanese healthy participants. Dose of TAK-071 was based on 24-hour safety, tolerability, and preliminary plasma PK data from Cohort 18. TAK-071 placebo-matching capsule, orally, once on Day 1 followed by donepezil placebo-matching tablet, orally on Day 2 to non-Japanese healthy participants. TAK-071 placebo-matching capsule, orally, once on Day 1 followed by donepezil 10 mg tablet, orally, on Day 2 to non-Japanese healthy participants. TAK-071 40 mg capsule, orally, once on Day 1 followed by donepezil 10 mg, tablets, orally, once on Day 2 to non-Japanese healthy participants. Dose of TAK-071 was based on 24-hour safety, tolerability, and preliminary plasma PK data from Cohort 19. TAK-071 60 mg capsule, orally, once on Day 1 followed by donepezil 10 mg, tablets, orally, once on Day 2 to non-Japanese healthy participants. Dose of TAK-071 was based on 24-hour safety and tolerability data from Cohort 20. TAK-071 80 mg capsule, orally, once on Day 1, followed by donepezil 10 mg, tablets, orally, once on Day 2 to non-Japanese healthy participants. Dose of TAK-071 was based on 24-hour safety and tolerability data from Cohort 21.
Period Title: Overall Study
STARTED 17 6 6 6 6 6 7 6 6 6 6 6 6 6 6 3 5 5 5 0 4 4 4 6 6 9 9 5 6 6
COMPLETED 16 6 6 6 6 6 6 6 6 6 5 6 6 6 6 3 5 5 5 0 4 4 4 6 6 9 9 5 6 6
NOT COMPLETED 1 0 0 0 0 0 1 0 0 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0

Baseline Characteristics

Arm/Group Title SRD: Placebo Cohorts 1-6, 18 and 19 SRD: Cohort 1: TAK-071 1 mg SRD: Cohort 2: TAK-071 3 mg SRD: Cohort 3: TAK-071 9 mg SRD: Cohort 4: TAK-071 20 mg SRD: Cohort 5: TAK-071 40 mg SRD: Cohort 6: TAK-071 80 mg MRD: Placebo Cohorts 7-9 MRD: Cohort 7: TAK-071 3 mg MRD: Cohort 8: TAK-071 9 mg MRD: Cohort 9: TAK-071 15 mg MRD: TAK-071 Placebo Cohorts 10-12+Donepezil MRD: Cohort 10: TAK-071 3 mg+Donepezil 5 mg MRD: Cohort 11: TAK-071 9 mg + Donepezil 5 mg MRD: Cohort 12: TAK-071 15 mg+Donepezil 5 mg MRD: Placebo Cohorts 13-15 MRD: Cohort 13: TAK-071 3 mg MRD: Cohort 14: TAK-071 9 mg MRD: Cohort 15: TAK-071 15 mg Cohort 16 Bioavailability (BA)/Food Effect: Cohort 17 Sequence ABC BA/Food Effect: Cohort 17 Sequence BCA BA/Food Effect: Cohort 17 Sequence CAB SRD: Cohort 18: TAK-071 120 mg SRD: Cohort 19: TAK-071 160 mg SRD: TAK-071 Placebo+Donepezil Placebo SRD: TAK-071 Placebo+Donepezil SRD: Cohort 20: TAK-071 40 mg+Donepezil SRD: Cohort 21: TAK-071 60 mg+Donepezil SRD: Cohort 22: TAK-071 80 mg+Donepezil Total
Arm/Group Description TAK-071 placebo-matching capsules, orally, once on Day 1 to non-Japanese healthy participants in the single-rising dose (SRD) period. TAK-071 1 mg, capsule, orally, once on Day 1 to non-Japanese healthy participants. TAK-071 3 mg capsule, orally, once on Day 1 to non-Japanese healthy participants. Dose of TAK-071 was based on the 24-hour post-dose safety, tolerability and pharmacokinetic (PK) data from cohort 1. TAK-071 9 mg capsule, orally, once on Day 1 to non-Japanese healthy participants. Dose of TAK-071 was based on 24-hour safety, tolerability, and preliminary plasma PK and 12-hour CSF PK data. TAK-071 20 mg capsule, orally, once on Day 1 to non-Japanese healthy participants. Dose of TAK-071 was based on the 24-hour post-dose safety and tolerability data from previous cohort. TAK-071 40 mg capsule, orally, once on Day 1 to non-Japanese healthy participants. Dose of TAK-071 will be based on 24-hour safety, tolerability, and preliminary plasma PK data from Cohort 4. TAK-071 80 mg capsules, orally, once on Day 1 to non-Japanese healthy participants. Dose of TAK-071 was based on 24-hour safety, tolerability, and preliminary plasma PK data from Cohort 5 TAK-071 placebo-matching capsule, orally, once on Day 1 to non-Japanese healthy participants in the multiple-rising dose (MRD) period. TAK-071 3 mg capsules, orally, once daily from Day 1 up to Day 21 to non-Japanese healthy participants. Dose of TAK-071 was based on 24-hour safety and tolerability from Cohort 4 and the 24-hour preliminary plasma PK and 12-hour CSF PK data from Cohort 3. TAK-071 9 mg capsules, orally, once daily from Day 1 up to Day 21 to non-Japanese healthy participants. Dose of TAK-071 was based on safety, tolerability and available PK data arising from the ongoing SRD part and previous MRD cohort. TAK-071 15 mg capsule, orally, once on Day 1, followed by a washout period of 7 days, then TAK-071 once daily for 21 days to non-Japanese healthy participants. Dose of TAK-071 will be based on safety, tolerability and available PK data arising from the ongoing SRD part and previous MRD cohort. TAK-071 placebo-matching capsule, orally, once daily along with donepezil 5 mg, tablets, orally, once daily from Day 1 up to Day 21 to non-Japanese healthy participants who were pre-treated with donepezil 5 mg, tablet, once daily for 3 weeks prior to administration of TAK-071. TAK-071 3 mg capsules, orally, once daily along with donepezil 5 mg, tablets, orally, once daily from Day 1 up to Day 21 to non-Japanese healthy participants who were pre-treated with donepezil 5 mg, tablet, once daily for 3 weeks prior to administration of TAK-071. Dose of TAK-071 was same as the dose used in MRD Cohort 7. TAK-071 9 mg capsules, orally, once daily along with donepezil 5 mg, tablets, orally, once daily from Day 1 up to Day 21 to non-Japanese healthy participants who were pre-treated with donepezil 5 mg, tablet, once daily for 3 weeks prior to administration of TAK-071. Dose of TAK-071 was same as the dose used in MRD Cohort 8. TAK-071 15 mg capsule, orally, once daily along with donepezil 5 mg, tablets, orally, once daily from Day 1 up to Day 21 to non-Japanese healthy participants who were pre-treated with donepezil 5 mg, tablet, once daily for 3 weeks prior to administration of TAK-071. Dose of TAK-071 was same as the dose used in MRD Cohort 9. TAK-071 placebo-matching capsule, orally, once on Day 1 to Japanese healthy participants. TAK-071 3 mg capsule, orally, once on Day 1, followed by a washout period of 7 days, then TAK-071 once daily for 21 days to Japanese healthy participants. Dose of TAK-071 was same as the dose used in MRD Cohort 7. TAK-071 9 mg capsule or matching placebo, orally, once on Day 1, followed by a washout period of 7 days, then TAK-071 once daily for 21 days to Japanese healthy participants. Dose of TAK-071 was same as the dose used in MRD Cohort 8. TAK-071 15 mg capsule, orally, once on Day 1, followed by a washout period of 7 days, then TAK-071 once daily for 21 days to Japanese healthy participants. Dose of TAK-071 was same as the dose used in MRD Cohort 9. TAK-071 capsule, orally, once on Day 1 for 21 days, followed by a washout period of 21 days, or placebo matching tablets, orally, once on Day 1 for 21 days. Donepezil was delivered as 5 mg tablet, orally, once followed by 10 mg tablet, orally, once in run-in period. A: TAK-071 10 mg capsule, orally once on Day 1 in the fasted state in Period 1, followed by B: TAK-071 10 mg tablet, orally, once on Day 1 in the fasted state in Period 2, followed by C: TAK-071 10 mg tablet, orally, once on Day 1 in the fed state in Period 3 in non-Japanese healthy participants. There was a 21-day washout after each period. B: TAK-071 10 mg tablet, orally, once on Day 1 in the fasted state in Period 1, followed by C: TAK-071 10 mg tablet, orally, once on Day 1 in the Fed state in Period 2, followed by A: TAK-071 10 mg capsule, orally once on Day 1 in the fasted state Period 3 in non-Japanese healthy participants. There was a 21-day washout after each period. C: TAK-071 10 mg tablet, orally, once on Day 1 in the fed state in Period 1, followed by A: TAK-071 10 mg capsule, orally once on Day 1 in the fasted state in Period 2, followed by B: TAK-20 10 mg tablet, orally, once on Day 1 in the fasted state in Period 3 in non-Japanese healthy participants. There was a 21-day washout after each period. TAK-071 120 mg capsule, orally, once on Day 1 to non-Japanese healthy participants. Dose of TAK-071 was based on 24-hour safety, tolerability, and preliminary plasma PK data from Cohort 6. TAK-071 160 mg capsule, orally, once on Day 1 to non-Japanese healthy participants. Dose of TAK-071 was based on 24-hour safety, tolerability, and preliminary plasma PK data from Cohort 18. TAK-071 placebo-matching capsule, orally, once on Day 1 followed by donepezil placebo-matching tablet, orally on Day 2 to non-Japanese healthy participants. TAK-071 placebo-matching capsule, orally, once on Day 1 followed by donepezil 10 mg tablet, orally, on Day 2 to non-Japanese healthy participants. TAK-071 40 mg capsule, orally, once on Day 1 followed by donepezil 10 mg, tablets, orally, once on Day 2 to non-Japanese healthy participants. Dose of TAK-071 was based on 24-hour safety, tolerability, and preliminary plasma PK data from Cohort 19. TAK-071 60 mg capsule, orally, once on Day 1 followed by donepezil 10 mg, tablets, orally, once on Day 2 to non-Japanese healthy participants. Dose of TAK-071 was based on 24-hour safety and tolerability data from Cohort 20. TAK-071 80 mg capsule, orally, once on Day 1, followed by donepezil 10 mg, tablets, orally, once on Day 2 to non-Japanese healthy participants. Dose of TAK-071 was based on 24-hour safety and tolerability data from Cohort 21. Total of all reporting groups
Overall Participants 16 6 6 6 6 6 6 6 6 6 6 6 6 6 6 3 5 5 5 0 4 4 4 6 6 9 9 5 6 6 177
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]
33.2
(6.46)
34.7
(4.32)
32.8
(9.43)
39.5
(11.33)
41.7
(9.33)
36.3
(8.16)
29.7
(8.12)
37.7
(6.56)
33.2
(7.78)
31.2
(8.59)
39.2
(6.71)
38.7
(6.31)
36.5
(6.53)
35.3
(7.17)
36.7
(9.54)
37.7
(3.79)
38.2
(10.99)
34.8
(6.42)
36.2
(8.67)
32.3
(7.37)
38.3
(8.88)
30.0
(2.45)
31.8
(10.26)
31.7
(6.95)
38.0
(9.18)
36.8
(9.82)
38.6
(13.20)
32.2
(6.77)
35.8
(9.47)
36.4
(9.36)
Sex: Female, Male (Count of Participants)
Female
1
6.3%
2
33.3%
0
0%
0
0%
2
33.3%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
NaN
0
0%
0
0%
0
0%
0
0%
2
33.3%
1
11.1%
1
11.1%
0
0%
2
33.3%
11
183.3%
Male
15
93.8%
4
66.7%
6
100%
6
100%
4
66.7%
6
100%
6
100%
6
100%
6
100%
6
100%
6
100%
6
100%
6
100%
6
100%
6
100%
3
100%
5
100%
5
100%
5
100%
4
Infinity
4
100%
4
100%
6
150%
6
100%
7
116.7%
8
88.9%
4
44.4%
6
120%
4
66.7%
166
2766.7%
Race/Ethnicity, Customized (Count of Participants)
Hispanic or Latino
2
12.5%
3
50%
0
0%
1
16.7%
2
33.3%
2
33.3%
3
50%
1
16.7%
0
0%
2
33.3%
3
50%
1
16.7%
2
33.3%
0
0%
2
33.3%
0
0%
0
0%
0
0%
0
0%
0
NaN
1
25%
1
25%
2
50%
1
16.7%
5
83.3%
2
22.2%
1
11.1%
1
20%
3
50%
41
683.3%
Not Hispanic or Latino
14
87.5%
3
50%
6
100%
5
83.3%
4
66.7%
4
66.7%
3
50%
5
83.3%
6
100%
4
66.7%
3
50%
5
83.3%
4
66.7%
6
100%
4
66.7%
3
100%
5
100%
5
100%
5
100%
4
Infinity
3
75%
3
75%
4
100%
5
83.3%
4
66.7%
7
77.8%
4
44.4%
5
100%
3
50%
136
2266.7%
Race/Ethnicity, Customized (Count of Participants)
American Indian or Alaska Native
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
NaN
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
Asian
2
12.5%
1
16.7%
0
0%
0
0%
0
0%
1
16.7%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
1
16.7%
1
16.7%
3
100%
5
100%
5
100%
5
100%
0
NaN
0
0%
0
0%
0
0%
1
16.7%
0
0%
1
11.1%
0
0%
1
20%
0
0%
27
450%
Black or African American
5
31.3%
1
16.7%
3
50%
3
50%
1
16.7%
0
0%
2
33.3%
2
33.3%
3
50%
2
33.3%
0
0%
4
66.7%
2
33.3%
2
33.3%
1
16.7%
0
0%
0
0%
0
0%
0
0%
2
Infinity
0
0%
1
25%
1
25%
1
16.7%
3
50%
2
22.2%
0
0%
2
40%
1
16.7%
44
733.3%
Native Hawaiian or Other Pacific Islander
0
0%
0
0%
1
16.7%
0
0%
1
16.7%
0
0%
1
16.7%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
NaN
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
1
11.1%
0
0%
0
0%
4
66.7%
White
8
50%
3
50%
2
33.3%
3
50%
4
66.7%
5
83.3%
3
50%
4
66.7%
2
33.3%
4
66.7%
5
83.3%
1
16.7%
4
66.7%
3
50%
4
66.7%
0
0%
0
0%
0
0%
0
0%
1
Infinity
4
100%
3
75%
5
125%
3
50%
6
100%
6
66.7%
3
33.3%
3
60%
5
83.3%
94
1566.7%
Multiracial
1
6.3%
1
16.7%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
1
16.7%
0
0%
1
16.7%
1
16.7%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
1
Infinity
0
0%
0
0%
0
0%
1
16.7%
0
0%
0
0%
1
11.1%
0
0%
0
0%
8
133.3%
Region of Enrollment (Count of Participants)
United States
16
100%
6
100%
6
100%
6
100%
6
100%
6
100%
6
100%
6
100%
6
100%
6
100%
6
100%
6
100%
6
100%
6
100%
6
100%
3
100%
5
100%
5
100%
5
100%
0
NaN
4
100%
4
100%
4
100%
6
100%
6
100%
9
100%
9
100%
5
100%
6
100%
6
100%
177
100%
Height (cm) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [cm]
175.8
(6.31)
169.0
(5.97)
175.0
(6.99)
179.3
(8.14)
172.3
(6.89)
175.8
(7.31)
179.8
(7.70)
173.0
(9.63)
178.8
(6.46)
172.8
(5.12)
174.7
(6.89)
175.3
(6.53)
177.0
(8.20)
176.2
(4.54)
168.0
(8.72)
172.3
(2.08)
171.2
(8.96)
172.8
(6.10)
178.2
(7.33)
178.8
(5.06)
175.8
(8.42)
175.3
(5.80)
173.0
(4.77)
174.8
(5.56)
175.2
(13.07)
173.9
(7.61)
178.4
(11.28)
174.7
(5.47)
170.8
(10.03)
174.5
(9.64)
Weight (kg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg]
80.77
(7.563)
71.80
(11.927)
73.25
(12.314)
85.35
(9.712)
80.35
(7.076)
82.58
(9.870)
80.00
(10.942)
78.05
(10.936)
84.22
(11.284)
76.73
(10.094)
75.33
(14.062)
81.93
(10.508)
76.55
(8.147)
76.23
(9.066)
76.72
(9.972)
69.63
(13.668)
69.52
(7.253)
67.72
(14.487)
74.72
(12.583)
79.73
(5.421)
83.85
(11.356)
75.53
(10.529)
78.63
(12.980)
78.42
(11.553)
77.58
(12.727)
77.66
(8.549)
87.28
(11.637)
72.25
(6.339)
70.78
(10.039)
77.09
(10.857)
Body Mass Index (BMI) (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]
26.18
(2.349)
24.99
(2.827)
23.82
(3.090)
26.50
(2.018)
27.13
(2.766)
26.65
(1.895)
24.65
(1.895)
26.04
(2.596)
26.30
(2.966)
25.71
(3.327)
24.58
(3.503)
26.59
(2.428)
24.46
(2.344)
24.52
(2.267)
27.10
(2.066)
23.38
(4.074)
23.69
(1.113)
22.56
(3.615)
23.45
(3.032)
24.95
(1.237)
27.06
(2.221)
24.66
(3.873)
26.19
(3.611)
25.60
(3.265)
25.21
(2.721)
25.66
(2.078)
27.36
(1.767)
23.73
(2.388)
24.65
(1.432)
25.30
(2.351)
Smoking Classification (Count of Participants)
Never Smoked
15
93.8%
6
100%
6
100%
4
66.7%
6
100%
5
83.3%
6
100%
5
83.3%
5
83.3%
5
83.3%
4
66.7%
5
83.3%
3
50%
5
83.3%
6
100%
2
66.7%
5
100%
3
60%
5
100%
4
Infinity
4
100%
4
100%
6
150%
4
66.7%
8
133.3%
8
88.9%
3
33.3%
6
120%
6
100%
154
2566.7%
Current Smoker
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
NaN
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
Ex-smoker
1
6.3%
0
0%
0
0%
2
33.3%
0
0%
1
16.7%
0
0%
1
16.7%
1
16.7%
1
16.7%
2
33.3%
1
16.7%
3
50%
1
16.7%
0
0%
1
33.3%
0
0%
2
40%
0
0%
0
NaN
0
0%
0
0%
0
0%
2
33.3%
1
16.7%
1
11.1%
2
22.2%
0
0%
0
0%
23
383.3%
Alcohol Classification (Count of Participants)
Never Drunk
12
75%
5
83.3%
6
100%
6
100%
6
100%
4
66.7%
6
100%
6
100%
5
83.3%
6
100%
4
66.7%
5
83.3%
6
100%
3
50%
5
83.3%
2
66.7%
4
80%
5
100%
4
80%
4
Infinity
4
100%
3
75%
6
150%
4
66.7%
8
133.3%
8
88.9%
5
55.6%
6
120%
6
100%
154
2566.7%
Current Drinker
4
25%
1
16.7%
0
0%
0
0%
0
0%
2
33.3%
0
0%
0
0%
1
16.7%
0
0%
2
33.3%
1
16.7%
0
0%
3
50%
1
16.7%
1
33.3%
1
20%
0
0%
1
20%
0
NaN
0
0%
1
25%
0
0%
2
33.3%
1
16.7%
1
11.1%
0
0%
0
0%
0
0%
23
383.3%
Ex-drinker
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
NaN
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
Xanthine/Caffeine Consumption (Count of Participants)
Yes
2
12.5%
0
0%
1
16.7%
2
33.3%
3
50%
1
16.7%
0
0%
0
0%
0
0%
0
0%
3
50%
1
16.7%
1
16.7%
0
0%
0
0%
3
100%
0
0%
1
20%
2
40%
1
Infinity
3
75%
1
25%
2
50%
3
50%
6
100%
2
22.2%
1
11.1%
1
20%
0
0%
40
666.7%
No
14
87.5%
6
100%
5
83.3%
4
66.7%
3
50%
5
83.3%
6
100%
6
100%
6
100%
6
100%
3
50%
5
83.3%
5
83.3%
6
100%
6
100%
0
0%
5
100%
4
80%
3
60%
3
Infinity
1
25%
3
75%
4
100%
3
50%
3
50%
7
77.8%
4
44.4%
5
100%
6
100%
137
2283.3%
Female Reproductive Status (Count of Participants)
Postmenopausal
0
0%
0
0%
0
0%
0
0%
1
16.7%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
NaN
0
0%
0
0%
0
0%
0
0%
2
33.3%
1
11.1%
1
11.1%
0
0%
1
16.7%
6
100%
Surgically Sterile
1
6.3%
2
33.3%
0
0%
0
0%
1
16.7%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
NaN
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
1
16.7%
5
83.3%
Female of Childbearing Potential
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
NaN
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
N/A (Subject is Male)
15
93.8%
4
66.7%
6
100%
6
100%
4
66.7%
6
100%
6
100%
6
100%
6
100%
6
100%
6
100%
6
100%
6
100%
6
100%
6
100%
3
100%
5
100%
5
100%
5
100%
4
Infinity
4
100%
4
100%
6
150%
6
100%
7
116.7%
8
88.9%
4
44.4%
6
120%
4
66.7%
166
2766.7%

Outcome Measures

1. Primary Outcome
Title Percentage of Participants Who Experienced at Least One Treatment-Emergent Adverse Event (TEAE)
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 with an onset that occurs or gets worse after receiving study drug.
Time Frame Day 1 up to Day 41

Outcome Measure Data

Analysis Population Description
Safety Analysis Set (SAS) included all randomized participants who received at least 1 dose of study drug.
Arm/Group Title SRD: Placebo Cohorts 1-6, 18 and 19 SRD: Cohort 1: TAK-071 1 mg SRD: Cohort 2: TAK-071 3 mg SRD: Cohort 3: TAK-071 9 mg SRD: Cohort 4: TAK-071 20 mg SRD: Cohort 5: TAK-071 40 mg SRD: Cohort 6: TAK-071 80 mg MRD: Placebo Cohorts 7-9 MRD: Cohort 7: TAK-071 3 mg MRD: Cohort 8: TAK-071 9 mg MRD: Cohort 9: TAK-071 15 mg MRD: TAK-071 Placebo Cohorts 10-12+Donepezil MRD: Cohort 10: TAK-071 3 mg+Donepezil 5 mg MRD: Cohort 11: TAK-071 9 mg + Donepezil 5 mg MRD: Cohort 12: TAK-071 15 mg+Donepezil 5 mg MRD: Placebo Cohorts 13-15 MRD: Cohort 13: TAK-071 3 mg MRD: Cohort 14: TAK-071 9 mg MRD: Cohort 15: TAK-071 15 mg Bioavailability (BA)/Food Effect: Cohort 17 Regimen A BA/Food Effect: Cohort 17 Regimen B BA/Food Effect: Cohort 17 Regimen C SRD: Cohort 18: TAK-071 120 mg SRD: Cohort 19: TAK-071 160 mg SRD: TAK-071 Placebo+Donepezil Placebo SRD: TAK-071 Placebo+Donepezil SRD: Cohort 20: TAK-071 40 mg+Donepezil SRD: Cohort 21: TAK-071 60 mg+Donepezil SRD: Cohort 22: TAK-071 80 mg+Donepezil
Arm/Group Description TAK-071 placebo-matching capsules, orally, once on Day 1 to non-Japanese healthy participants in the single-rising dose (SRD) period. TAK-071 1 mg, capsule, orally, once on Day 1 to non-Japanese healthy participants. TAK-071 3 mg capsule, orally, once on Day 1 to non-Japanese healthy participants. Dose of TAK-071 was based on the 24-hour post-dose safety, tolerability and pharmacokinetic (PK) data from cohort 1. TAK-071 9 mg capsule, orally, once on Day 1 to non-Japanese healthy participants. Dose of TAK-071 was based on 24-hour safety, tolerability, and preliminary plasma PK and 12-hour CSF PK data. TAK-071 20 mg capsule, orally, once on Day 1 to non-Japanese healthy participants. Dose of TAK-071 was based on the 24-hour post-dose safety and tolerability data from previous cohort. TAK-071 40 mg capsule, orally, once on Day 1 to non-Japanese healthy participants. Dose of TAK-071 will be based on 24-hour safety, tolerability, and preliminary plasma PK data from Cohort 4. TAK-071 80 mg capsules, orally, once on Day 1 to non-Japanese healthy participants. Dose of TAK-071 was based on 24-hour safety, tolerability, and preliminary plasma PK data from Cohort 5 TAK-071 placebo-matching capsule, orally, once on Day 1 to non-Japanese healthy participants in the multiple-rising dose (MRD) period. TAK-071 3 mg capsules, orally, once daily from Day 1 up to Day 21 to non-Japanese healthy participants. Dose of TAK-071 was based on 24-hour safety and tolerability from Cohort 4 and the 24-hour preliminary plasma PK and 12-hour CSF PK data from Cohort 3. TAK-071 9 mg capsules, orally, once daily from Day 1 up to Day 21 to non-Japanese healthy participants. Dose of TAK-071 was based on safety, tolerability and available PK data arising from the ongoing SRD part and previous MRD cohort. TAK-071 15 mg capsule, orally, once on Day 1, followed by a washout period of 7 days, then TAK-071 once daily for 21 days to non-Japanese healthy participants. Dose of TAK-071 will be based on safety, tolerability and available PK data arising from the ongoing SRD part and previous MRD cohort. TAK-071 placebo-matching capsule, orally, once daily along with donepezil 5 mg, tablets, orally, once daily from Day 1 up to Day 21 to non-Japanese healthy participants who were pre-treated with donepezil 5 mg, tablet, once daily for 3 weeks prior to administration of TAK-071. TAK-071 3 mg capsules, orally, once daily along with donepezil 5 mg, tablets, orally, once daily from Day 1 up to Day 21 to non-Japanese healthy participants who were pre-treated with donepezil 5 mg, tablet, once daily for 3 weeks prior to administration of TAK-071. Dose of TAK-071 was same as the dose used in MRD Cohort 7. TAK-071 9 mg capsules, orally, once daily along with donepezil 5 mg, tablets, orally, once daily from Day 1 up to Day 21 to non-Japanese healthy participants who were pre-treated with donepezil 5 mg, tablet, once daily for 3 weeks prior to administration of TAK-071. Dose of TAK-071 was same as the dose used in MRD Cohort 8. TAK-071 15 mg capsule, orally, once daily along with donepezil 5 mg, tablets, orally, once daily from Day 1 up to Day 21 to non-Japanese healthy participants who were pre-treated with donepezil 5 mg, tablet, once daily for 3 weeks prior to administration of TAK-071. Dose of TAK-071 was same as the dose used in MRD Cohort 9. TAK-071 placebo-matching capsule, orally, once on Day 1 to Japanese healthy participants. TAK-071 3 mg capsule, orally, once on Day 1, followed by a washout period of 7 days, then TAK-071 once daily for 21 days to Japanese healthy participants. Dose of TAK-071 was same as the dose used in MRD Cohort 7. TAK-071 9 mg capsule or matching placebo, orally, once on Day 1, followed by a washout period of 7 days, then TAK-071 once daily for 21 days to Japanese healthy participants. Dose of TAK-071 was same as the dose used in MRD Cohort 8. TAK-071 15 mg capsule, orally, once on Day 1, followed by a washout period of 7 days, then TAK-071 once daily for 21 days to Japanese healthy participants. Dose of TAK-071 was same as the dose used in MRD Cohort 9. TAK-071 10 mg capsule, orally once on Day 1 in the fasted state in Period 1 or Period 2 or Period 3 TAK-071 10 mg tablet, orally, once on Day 1 in the fasted state in Period 1 or Period 2 or Period 3 TAK-071 10 mg tablet, orally, once on Day 1 in the fed state in Period 1 or Period 2 or Period 3 TAK-071 120 mg capsule, orally, once on Day 1 to non-Japanese healthy participants. Dose of TAK-071 was based on 24-hour safety, tolerability, and preliminary plasma PK data from Cohort 6. TAK-071 160 mg capsule, orally, once on Day 1 to non-Japanese healthy participants. Dose of TAK-071 was based on 24-hour safety, tolerability, and preliminary plasma PK data from Cohort 18. TAK-071 placebo-matching capsule, orally, once on Day 1 followed by donepezil placebo-matching tablet, orally on Day 2 to non-Japanese healthy participants. TAK-071 placebo-matching capsule, orally, once on Day 1 followed by donepezil 10 mg tablet, orally, on Day 2 to non-Japanese healthy participants. TAK-071 40 mg capsule, orally, once on Day 1 followed by donepezil 10 mg, tablets, orally, once on Day 2 to non-Japanese healthy participants. Dose of TAK-071 was based on 24-hour safety, tolerability, and preliminary plasma PK data from Cohort 19. TAK-071 60 mg capsule, orally, once on Day 1 followed by donepezil 10 mg, tablets, orally, once on Day 2 to non-Japanese healthy participants. Dose of TAK-071 was based on 24-hour safety and tolerability data from Cohort 20. TAK-071 80 mg capsule, orally, once on Day 1, followed by donepezil 10 mg, tablets, orally, once on Day 2 to non-Japanese healthy participants. Dose of TAK-071 was based on 24-hour safety and tolerability data from Cohort 21.
Measure Participants 16 6 6 6 6 6 6 6 6 6 6 6 6 6 6 3 5 5 5 12 12 12 6 6 9 9 5 6 6
Number [percentage of participants]
25.0
156.3%
33.3
555%
0
0%
66.7
1111.7%
33.3
555%
0
0%
16.7
278.3%
50.0
833.3%
16.7
278.3%
16.7
278.3%
50.0
833.3%
33.3
555%
33.3
555%
50.0
833.3%
50.0
833.3%
66.7
2223.3%
40.0
800%
40.0
800%
60.0
1200%
16.7
Infinity
8.3
207.5%
8.3
207.5%
0
0%
33.3
555%
44.4
740%
55.6
617.8%
80.0
888.9%
100
2000%
83.3
1388.3%
2. Primary Outcome
Title Percentage of Participants Who Meet the Markedly Abnormal Criteria for Clinical Laboratory Tests at Least Once Post-dose
Description Clinical laboratory tests included serum chemistry, hematology, coagulation and urinalysis. ULN=upper limit of normal range.
Time Frame Day 1 up to Day 41

Outcome Measure Data

Analysis Population Description
SAS included all randomized participants who received at least 1 dose of study drug.
Arm/Group Title SRD: Placebo Cohorts 1-6, 18 and 19 SRD: Cohort 1: TAK-071 1 mg SRD: Cohort 2: TAK-071 3 mg SRD: Cohort 3: TAK-071 9 mg SRD: Cohort 4: TAK-071 20 mg SRD: Cohort 5: TAK-071 40 mg SRD: Cohort 6: TAK-071 80 mg MRD: Placebo Cohorts 7-9 MRD: Cohort 7: TAK-071 3 mg MRD: Cohort 8: TAK-071 9 mg MRD: Cohort 9: TAK-071 15 mg MRD: TAK-071 Placebo Cohorts 10-12+Donepezil MRD: Cohort 10: TAK-071 3 mg+Donepezil 5 mg MRD: Cohort 11: TAK-071 9 mg + Donepezil 5 mg MRD: Cohort 12: TAK-071 15 mg+Donepezil 5 mg MRD: Placebo Cohorts 13-15 MRD: Cohort 13: TAK-071 3 mg MRD: Cohort 14: TAK-071 9 mg MRD: Cohort 15: TAK-071 15 mg Bioavailability (BA)/Food Effect: Cohort 17 Regimen A BA/Food Effect: Cohort 17 Regimen B BA/Food Effect: Cohort 17 Regimen C SRD: Cohort 18: TAK-071 120 mg SRD: Cohort 19: TAK-071 160 mg SRD: TAK-071 Placebo+Donepezil Placebo SRD: TAK-071 Placebo+Donepezil SRD: Cohort 20: TAK-071 40 mg+Donepezil SRD: Cohort 21: TAK-071 60 mg+Donepezil SRD: Cohort 22: TAK-071 80 mg+Donepezil
Arm/Group Description TAK-071 placebo-matching capsules, orally, once on Day 1 to non-Japanese healthy participants in the single-rising dose (SRD) period. TAK-071 1 mg, capsule, orally, once on Day 1 to non-Japanese healthy participants. TAK-071 3 mg capsule, orally, once on Day 1 to non-Japanese healthy participants. Dose of TAK-071 was based on the 24-hour post-dose safety, tolerability and pharmacokinetic (PK) data from cohort 1. TAK-071 9 mg capsule, orally, once on Day 1 to non-Japanese healthy participants. Dose of TAK-071 was based on 24-hour safety, tolerability, and preliminary plasma PK and 12-hour CSF PK data. TAK-071 20 mg capsule, orally, once on Day 1 to non-Japanese healthy participants. Dose of TAK-071 was based on the 24-hour post-dose safety and tolerability data from previous cohort. TAK-071 40 mg capsule, orally, once on Day 1 to non-Japanese healthy participants. Dose of TAK-071 will be based on 24-hour safety, tolerability, and preliminary plasma PK data from Cohort 4. TAK-071 80 mg capsules, orally, once on Day 1 to non-Japanese healthy participants. Dose of TAK-071 was based on 24-hour safety, tolerability, and preliminary plasma PK data from Cohort 5 TAK-071 placebo-matching capsule, orally, once on Day 1 to non-Japanese healthy participants in the multiple-rising dose (MRD) period. TAK-071 3 mg capsules, orally, once daily from Day 1 up to Day 21 to non-Japanese healthy participants. Dose of TAK-071 was based on 24-hour safety and tolerability from Cohort 4 and the 24-hour preliminary plasma PK and 12-hour CSF PK data from Cohort 3. TAK-071 9 mg capsules, orally, once daily from Day 1 up to Day 21 to non-Japanese healthy participants. Dose of TAK-071 was based on safety, tolerability and available PK data arising from the ongoing SRD part and previous MRD cohort. TAK-071 15 mg capsule, orally, once on Day 1, followed by a washout period of 7 days, then TAK-071 once daily for 21 days to non-Japanese healthy participants. Dose of TAK-071 will be based on safety, tolerability and available PK data arising from the ongoing SRD part and previous MRD cohort. TAK-071 placebo-matching capsule, orally, once daily along with donepezil 5 mg, tablets, orally, once daily from Day 1 up to Day 21 to non-Japanese healthy participants who were pre-treated with donepezil 5 mg, tablet, once daily for 3 weeks prior to administration of TAK-071. TAK-071 3 mg capsules, orally, once daily along with donepezil 5 mg, tablets, orally, once daily from Day 1 up to Day 21 to non-Japanese healthy participants who were pre-treated with donepezil 5 mg, tablet, once daily for 3 weeks prior to administration of TAK-071. Dose of TAK-071 was same as the dose used in MRD Cohort 7. TAK-071 9 mg capsules, orally, once daily along with donepezil 5 mg, tablets, orally, once daily from Day 1 up to Day 21 to non-Japanese healthy participants who were pre-treated with donepezil 5 mg, tablet, once daily for 3 weeks prior to administration of TAK-071. Dose of TAK-071 was same as the dose used in MRD Cohort 8. TAK-071 15 mg capsule, orally, once daily along with donepezil 5 mg, tablets, orally, once daily from Day 1 up to Day 21 to non-Japanese healthy participants who were pre-treated with donepezil 5 mg, tablet, once daily for 3 weeks prior to administration of TAK-071. Dose of TAK-071 was same as the dose used in MRD Cohort 9. TAK-071 placebo-matching capsule, orally, once on Day 1 to Japanese healthy participants. TAK-071 3 mg capsule, orally, once on Day 1, followed by a washout period of 7 days, then TAK-071 once daily for 21 days to Japanese healthy participants. Dose of TAK-071 was same as the dose used in MRD Cohort 7. TAK-071 9 mg capsule or matching placebo, orally, once on Day 1, followed by a washout period of 7 days, then TAK-071 once daily for 21 days to Japanese healthy participants. Dose of TAK-071 was same as the dose used in MRD Cohort 8. TAK-071 15 mg capsule, orally, once on Day 1, followed by a washout period of 7 days, then TAK-071 once daily for 21 days to Japanese healthy participants. Dose of TAK-071 was same as the dose used in MRD Cohort 9. TAK-071 10 mg capsule, orally once on Day 1 in the fasted state in Period 1 or Period 2 or Period 3 TAK-071 10 mg tablet, orally, once on Day 1 in the fasted state in Period 1 or Period 2 or Period 3 TAK-071 10 mg tablet, orally, once on Day 1 in the fed state in Period 1 or Period 2 or Period 3 TAK-071 120 mg capsule, orally, once on Day 1 to non-Japanese healthy participants. Dose of TAK-071 was based on 24-hour safety, tolerability, and preliminary plasma PK data from Cohort 6. TAK-071 160 mg capsule, orally, once on Day 1 to non-Japanese healthy participants. Dose of TAK-071 was based on 24-hour safety, tolerability, and preliminary plasma PK data from Cohort 18. TAK-071 placebo-matching capsule, orally, once on Day 1 followed by donepezil placebo-matching tablet, orally on Day 2 to non-Japanese healthy participants. TAK-071 placebo-matching capsule, orally, once on Day 1 followed by donepezil 10 mg tablet, orally, on Day 2 to non-Japanese healthy participants. TAK-071 40 mg capsule, orally, once on Day 1 followed by donepezil 10 mg, tablets, orally, once on Day 2 to non-Japanese healthy participants. Dose of TAK-071 was based on 24-hour safety, tolerability, and preliminary plasma PK data from Cohort 19. TAK-071 60 mg capsule, orally, once on Day 1 followed by donepezil 10 mg, tablets, orally, once on Day 2 to non-Japanese healthy participants. Dose of TAK-071 was based on 24-hour safety and tolerability data from Cohort 20. TAK-071 80 mg capsule, orally, once on Day 1, followed by donepezil 10 mg, tablets, orally, once on Day 2 to non-Japanese healthy participants. Dose of TAK-071 was based on 24-hour safety and tolerability data from Cohort 21.
Measure Participants 16 6 6 6 6 6 6 6 6 6 6 6 6 6 6 3 5 5 5 12 12 12 6 6 9 9 5 6 6
Bilirubin (>2.0 mg/dL, >34.2 umol/L)
0
0%
0
0%
0
0%
16.7
278.3%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
NaN
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
Creatine Kinase (>5*ULN)
6.3
39.4%
0
0%
0
0%
16.7
278.3%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
8.3
Infinity
0
0%
8.3
207.5%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
Blood Urea Nitrogen (>30 mg/dL, >10.7 mmol/L)
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
16.7
278.3%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
NaN
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
Prothrombin Intl. Normalized Ratio (>1.5*ULN)
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
16.7
278.3%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
NaN
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
Aspartate Aminotransferase (>3*ULN)
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
NaN
0
0%
8.3
207.5%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
3. Primary Outcome
Title Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose
Description Vital Sign measurements included systolic blood pressure (SBP), diastolic blood presssure (DBP), pulse, temperature, orthostatic SBP, orthostatic DBP and orthostatic pulse.
Time Frame Day 1 up to Day 41

Outcome Measure Data

Analysis Population Description
SAS included all randomized participants who received at least 1 dose of study drug.
Arm/Group Title SRD: Placebo Cohorts 1-6, 18 and 19 SRD: Cohort 1: TAK-071 1 mg SRD: Cohort 2: TAK-071 3 mg SRD: Cohort 3: TAK-071 9 mg SRD: Cohort 4: TAK-071 20 mg SRD: Cohort 5: TAK-071 40 mg SRD: Cohort 6: TAK-071 80 mg MRD: Placebo Cohorts 7-9 MRD: Cohort 7: TAK-071 3 mg MRD: Cohort 8: TAK-071 9 mg MRD: Cohort 9: TAK-071 15 mg MRD: TAK-071 Placebo Cohorts 10-12+Donepezil MRD: Cohort 10: TAK-071 3 mg+Donepezil 5 mg MRD: Cohort 11: TAK-071 9 mg + Donepezil 5 mg MRD: Cohort 12: TAK-071 15 mg+Donepezil 5 mg MRD: Placebo Cohorts 13-15 MRD: Cohort 13: TAK-071 3 mg MRD: Cohort 14: TAK-071 9 mg MRD: Cohort 15: TAK-071 15 mg Bioavailability (BA)/Food Effect: Cohort 17 Regimen A BA/Food Effect: Cohort 17 Regimen B BA/Food Effect: Cohort 17 Regimen C SRD: Cohort 18: TAK-071 120 mg SRD: Cohort 19: TAK-071 160 mg SRD: TAK-071 Placebo+Donepezil Placebo SRD: TAK-071 Placebo+Donepezil SRD: Cohort 20: TAK-071 40 mg+Donepezil SRD: Cohort 21: TAK-071 60 mg+Donepezil SRD: Cohort 22: TAK-071 80 mg+Donepezil
Arm/Group Description TAK-071 placebo-matching capsules, orally, once on Day 1 to non-Japanese healthy participants in the single-rising dose (SRD) period. TAK-071 1 mg, capsule, orally, once on Day 1 to non-Japanese healthy participants. TAK-071 3 mg capsule, orally, once on Day 1 to non-Japanese healthy participants. Dose of TAK-071 was based on the 24-hour post-dose safety, tolerability and pharmacokinetic (PK) data from cohort 1. TAK-071 9 mg capsule, orally, once on Day 1 to non-Japanese healthy participants. Dose of TAK-071 was based on 24-hour safety, tolerability, and preliminary plasma PK and 12-hour CSF PK data. TAK-071 20 mg capsule, orally, once on Day 1 to non-Japanese healthy participants. Dose of TAK-071 was based on the 24-hour post-dose safety and tolerability data from previous cohort. TAK-071 40 mg capsule, orally, once on Day 1 to non-Japanese healthy participants. Dose of TAK-071 will be based on 24-hour safety, tolerability, and preliminary plasma PK data from Cohort 4. TAK-071 80 mg capsules, orally, once on Day 1 to non-Japanese healthy participants. Dose of TAK-071 was based on 24-hour safety, tolerability, and preliminary plasma PK data from Cohort 5 TAK-071 placebo-matching capsule, orally, once on Day 1 to non-Japanese healthy participants in the multiple-rising dose (MRD) period. TAK-071 3 mg capsules, orally, once daily from Day 1 up to Day 21 to non-Japanese healthy participants. Dose of TAK-071 was based on 24-hour safety and tolerability from Cohort 4 and the 24-hour preliminary plasma PK and 12-hour CSF PK data from Cohort 3. TAK-071 9 mg capsules, orally, once daily from Day 1 up to Day 21 to non-Japanese healthy participants. Dose of TAK-071 was based on safety, tolerability and available PK data arising from the ongoing SRD part and previous MRD cohort. TAK-071 15 mg capsule, orally, once on Day 1, followed by a washout period of 7 days, then TAK-071 once daily for 21 days to non-Japanese healthy participants. Dose of TAK-071 will be based on safety, tolerability and available PK data arising from the ongoing SRD part and previous MRD cohort. TAK-071 placebo-matching capsule, orally, once daily along with donepezil 5 mg, tablets, orally, once daily from Day 1 up to Day 21 to non-Japanese healthy participants who were pre-treated with donepezil 5 mg, tablet, once daily for 3 weeks prior to administration of TAK-071. TAK-071 3 mg capsules, orally, once daily along with donepezil 5 mg, tablets, orally, once daily from Day 1 up to Day 21 to non-Japanese healthy participants who were pre-treated with donepezil 5 mg, tablet, once daily for 3 weeks prior to administration of TAK-071. Dose of TAK-071 was same as the dose used in MRD Cohort 7. TAK-071 9 mg capsules, orally, once daily along with donepezil 5 mg, tablets, orally, once daily from Day 1 up to Day 21 to non-Japanese healthy participants who were pre-treated with donepezil 5 mg, tablet, once daily for 3 weeks prior to administration of TAK-071. Dose of TAK-071 was same as the dose used in MRD Cohort 8. TAK-071 15 mg capsule, orally, once daily along with donepezil 5 mg, tablets, orally, once daily from Day 1 up to Day 21 to non-Japanese healthy participants who were pre-treated with donepezil 5 mg, tablet, once daily for 3 weeks prior to administration of TAK-071. Dose of TAK-071 was same as the dose used in MRD Cohort 9. TAK-071 placebo-matching capsule, orally, once on Day 1 to Japanese healthy participants. TAK-071 3 mg capsule, orally, once on Day 1, followed by a washout period of 7 days, then TAK-071 once daily for 21 days to Japanese healthy participants. Dose of TAK-071 was same as the dose used in MRD Cohort 7. TAK-071 9 mg capsule or matching placebo, orally, once on Day 1, followed by a washout period of 7 days, then TAK-071 once daily for 21 days to Japanese healthy participants. Dose of TAK-071 was same as the dose used in MRD Cohort 8. TAK-071 15 mg capsule, orally, once on Day 1, followed by a washout period of 7 days, then TAK-071 once daily for 21 days to Japanese healthy participants. Dose of TAK-071 was same as the dose used in MRD Cohort 9. TAK-071 10 mg capsule, orally once on Day 1 in the fasted state in Period 1 or Period 2 or Period 3 TAK-071 10 mg tablet, orally, once on Day 1 in the fasted state in Period 1 or Period 2 or Period 3 TAK-071 10 mg tablet, orally, once on Day 1 in the fed state in Period 1 or Period 2 or Period 3 TAK-071 120 mg capsule, orally, once on Day 1 to non-Japanese healthy participants. Dose of TAK-071 was based on 24-hour safety, tolerability, and preliminary plasma PK data from Cohort 6. TAK-071 160 mg capsule, orally, once on Day 1 to non-Japanese healthy participants. Dose of TAK-071 was based on 24-hour safety, tolerability, and preliminary plasma PK data from Cohort 18. TAK-071 placebo-matching capsule, orally, once on Day 1 followed by donepezil placebo-matching tablet, orally on Day 2 to non-Japanese healthy participants. TAK-071 placebo-matching capsule, orally, once on Day 1 followed by donepezil 10 mg tablet, orally, on Day 2 to non-Japanese healthy participants. TAK-071 40 mg capsule, orally, once on Day 1 followed by donepezil 10 mg, tablets, orally, once on Day 2 to non-Japanese healthy participants. Dose of TAK-071 was based on 24-hour safety, tolerability, and preliminary plasma PK data from Cohort 19. TAK-071 60 mg capsule, orally, once on Day 1 followed by donepezil 10 mg, tablets, orally, once on Day 2 to non-Japanese healthy participants. Dose of TAK-071 was based on 24-hour safety and tolerability data from Cohort 20. TAK-071 80 mg capsule, orally, once on Day 1, followed by donepezil 10 mg, tablets, orally, once on Day 2 to non-Japanese healthy participants. Dose of TAK-071 was based on 24-hour safety and tolerability data from Cohort 21.
Measure Participants 16 6 6 6 6 6 6 6 6 6 6 6 6 6 6 3 5 5 5 12 12 12 6 6 9 9 5 6 6
Systolic Blood Pressure (SBP), Supine, <85 mmHg
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
16.7
278.3%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
NaN
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
SBP, Supine, >180 mmHg
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
NaN
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
SBP, 5 minutes (min) Supine, <85 mmHg,
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
16.7
278.3%
0
0%
0
0%
0
0%
16.7
278.3%
0
0%
0
0%
0
0%
0
0%
0
0%
0
NaN
0
0%
8.3
207.5%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
SBP, 5 min Supine, >180 mmHg
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
NaN
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
SBP, 1 min Standing, <85 mmHg
0
0%
0
0%
0
0%
0
0%
16.7
278.3%
0
0%
0
0%
0
0%
16.7
278.3%
16.7
278.3%
0
0%
0
0%
16.7
278.3%
0
0%
0
0%
0
0%
0
0%
0
0%
20.0
400%
8.3
Infinity
8.3
207.5%
0
0%
16.7
417.5%
0
0%
0
0%
11.1
123.3%
0
0%
0
0%
0
0%
SBP, 1 min Standing, >180 mmHg
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
NaN
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
SBP, 3 min Standing, <85 mmHg
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
16.7
278.3%
0
0%
0
0%
16.7
278.3%
0
0%
0
0%
16.7
278.3%
33.3
555%
0
0%
0
0%
0
0%
0
0%
20.0
400%
8.3
Infinity
8.3
207.5%
0
0%
0
0%
16.7
278.3%
0
0%
11.1
123.3%
0
0%
0
0%
0
0%
SBP, 3 min Standing, >180 mmHg
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
NaN
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
Diastolic Blood Pressure (DBP), Supine, <50 mmHg
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
16.7
278.3%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
NaN
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
DBP, Supine, >110 mmHg
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
NaN
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
DBP, 5 min supine, <50 mmHg
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
16.7
278.3%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
NaN
8.3
207.5%
0
0%
0
0%
0
0%
0
0%
11.1
123.3%
0
0%
0
0%
0
0%
DBP, 5 min Supine, >110 mmHg
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
NaN
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
DBP, 1 min Standing, <50 mmHg
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
16.7
278.3%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
8.3
Infinity
8.3
207.5%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
DBP, 1 min Standing, >110 mmHg
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
16.7
278.3%
0
0%
0
0%
0
0%
20.0
400%
0
NaN
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
DBP, 3 min Standing, <50 mmHg
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
16.7
278.3%
0
0%
0
0%
0
0%
0
0%
0
0%
0
NaN
0
0%
0
0%
0
0%
0
0%
0
0%
11.1
123.3%
0
0%
0
0%
0
0%
DBP, 3 min Standing, >110 mmHg
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
16.7
278.3%
0
0%
0
0%
20.0
400%
0
0%
0
NaN
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
Pulse, Supine, <50 beats/min (bpm)
6.3
39.4%
33.3
555%
0
0%
0
0%
0
0%
16.7
278.3%
16.7
278.3%
16.7
278.3%
0
0%
16.7
278.3%
0
0%
0
0%
33.3
555%
50.0
833.3%
50.0
833.3%
0
0%
0
0%
0
0%
0
0%
16.7
Infinity
16.7
417.5%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
Pulse, Supine, >120 beats/min
6.3
39.4%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
NaN
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
Pulse, 5 min Supine, <50 beats/min
25.0
156.3%
0
0%
16.7
278.3%
0
0%
33.3
555%
16.7
278.3%
16.7
278.3%
33.3
555%
0
0%
33.3
555%
0
0%
16.7
278.3%
33.3
555%
16.7
278.3%
16.7
278.3%
33.3
1110%
60.0
1200%
40.0
800%
20.0
400%
33.3
Infinity
41.7
1042.5%
25.0
625%
66.7
1667.5%
0
0%
44.4
740%
22.2
246.7%
40.0
444.4%
33.3
666%
16.7
278.3%
Pulse, 5 min Supine, >120 beats/min
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
20.0
400%
0
NaN
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
Pulse, 1 min Standing, <50 beats/min
0
0%
0
0%
0
0%
0
0%
0
0%
16.7
278.3%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
20.0
400%
0
0%
0
NaN
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
Pulse, 1 min Standing, >120 beats/min
6.3
39.4%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
16.7
278.3%
16.7
278.3%
0
0%
0
0%
0
0%
0
0%
20.0
400%
40.0
800%
0
NaN
0
0%
0
0%
0
0%
16.7
278.3%
11.1
185%
0
0%
20.0
222.2%
0
0%
0
0%
Pulse, 3 min Standing, <50 beats/min
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
20.0
400%
0
0%
0
NaN
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
Pulse, 3 min Standing, >120 beats/min
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
16.7
278.3%
0
0%
0
0%
0
0%
0
0%
0
0%
40.0
800%
0
NaN
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
20.0
222.2%
0
0%
0
0%
Temperature, <35.6 Celsius (C)
0
0%
0
0%
16.7
278.3%
0
0%
0
0%
0
0%
33.3
555%
50.0
833.3%
16.7
278.3%
33.3
555%
16.7
278.3%
16.7
278.3%
33.3
555%
0
0%
33.3
555%
66.7
2223.3%
40.0
800%
20.0
400%
60.0
1200%
25.0
Infinity
0
0%
8.3
207.5%
0
0%
0
0%
0
0%
0
0%
40.0
444.4%
0
0%
16.7
278.3%
Temperature, >37.7 C
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
20.0
400%
0
0%
0
NaN
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
Orthostatic SBP, 1 min Standing-Supine, <=-20 mmHg
12.5
78.1%
0
0%
0
0%
0
0%
16.7
278.3%
16.7
278.3%
0
0%
16.7
278.3%
16.7
278.3%
0
0%
0
0%
50.0
833.3%
50.0
833.3%
50.0
833.3%
16.7
278.3%
0
0%
20.0
400%
40.0
800%
60.0
1200%
16.7
Infinity
0
0%
8.3
207.5%
33.3
832.5%
16.7
278.3%
22.2
370%
0
0%
40.0
444.4%
0
0%
16.7
278.3%
Orthostatic SBP, 3 min Standing-Supine, <=-20 mmHg
6.3
39.4%
0
0%
0
0%
0
0%
0
0%
0
0%
33.3
555%
16.7
278.3%
0
0%
33.3
555%
0
0%
16.7
278.3%
33.3
555%
50.0
833.3%
0
0%
0
0%
20.0
400%
40.0
800%
40.0
800%
16.7
Infinity
8.3
207.5%
0
0%
16.7
417.5%
16.7
278.3%
0
0%
0
0%
40.0
444.4%
16.7
334%
0
0%
Orthostatic DBP, 1 min Standing-Supine, <=-10 mmHg
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
16.7
278.3%
0
0%
0
0%
0
0%
16.7
278.3%
0
0%
16.7
278.3%
0
0%
0
0%
0
0%
20.0
400%
8.3
Infinity
0
0%
0
0%
16.7
417.5%
0
0%
0
0%
0
0%
20.0
222.2%
0
0%
0
0%
Orthostatic DBP, 3 min Standing-Supine, <=-10 mmHg
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
16.7
278.3%
0
0%
0
0%
16.7
278.3%
33.3
555%
0
0%
0
0%
0
0%
20.0
400%
20.0
400%
8.3
Infinity
0
0%
0
0%
16.7
417.5%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
Orthostatic Pulse, 1 min Standing-Supine >10 bpm
75.0
468.8%
0
0%
100
1666.7%
0
0%
100
1666.7%
100
1666.7%
100
1666.7%
66.7
1111.7%
100
1666.7%
100
1666.7%
0
0%
100
1666.7%
100
1666.7%
100
1666.7%
100
1666.7%
100
3333.3%
100
2000%
100
2000%
100
2000%
100
Infinity
100
2500%
100
2500%
100
2500%
100
1666.7%
88.9
1481.7%
100
1111.1%
100
1111.1%
100
2000%
100
1666.7%
Orthostatic Pulse, 3 min Standing-Supine >10 bpm
75.0
468.8%
0
0%
100
1666.7%
0
0%
100
1666.7%
100
1666.7%
100
1666.7%
66.7
1111.7%
100
1666.7%
100
1666.7%
0
0%
100
1666.7%
100
1666.7%
100
1666.7%
100
1666.7%
100
3333.3%
100
2000%
100
2000%
100
2000%
100
Infinity
100
2500%
100
2500%
100
2500%
100
1666.7%
88.9
1481.7%
100
1111.1%
100
1111.1%
100
2000%
100
1666.7%
4. Primary Outcome
Title Percentage of Participants Who Meet the Markedly Abnormal Criteria for 12-lead Electrocardiogram (ECG) Parameters at Least Once Post-dose
Description A standard 12-lead electrocardiogram (ECG) was performed. The percentage of participants with markedly abnormal ECG findings during the study.
Time Frame Day 1 up to Day 41

Outcome Measure Data

Analysis Population Description
SAS included all randomized participants who received at least 1 dose of study drug.
Arm/Group Title SRD: Placebo Cohorts 1-6, 18 and 19 SRD: Cohort 1: TAK-071 1 mg SRD: Cohort 2: TAK-071 3 mg SRD: Cohort 3: TAK-071 9 mg SRD: Cohort 4: TAK-071 20 mg SRD: Cohort 5: TAK-071 40 mg SRD: Cohort 6: TAK-071 80 mg MRD: Placebo Cohorts 7-9 MRD: Cohort 7: TAK-071 3 mg MRD: Cohort 8: TAK-071 9 mg MRD: Cohort 9: TAK-071 15 mg MRD: TAK-071 Placebo Cohorts 10-12+Donepezil MRD: Cohort 10: TAK-071 3 mg+Donepezil 5 mg MRD: Cohort 11: TAK-071 9 mg + Donepezil 5 mg MRD: Cohort 12: TAK-071 15 mg+Donepezil 5 mg MRD: Placebo Cohorts 13-15 MRD: Cohort 13: TAK-071 3 mg MRD: Cohort 14: TAK-071 9 mg MRD: Cohort 15: TAK-071 15 mg Bioavailability (BA)/Food Effect: Cohort 17 Regimen A BA/Food Effect: Cohort 17 Regimen B BA/Food Effect: Cohort 17 Regimen C SRD: Cohort 18: TAK-071 120 mg SRD: Cohort 19: TAK-071 160 mg SRD: TAK-071 Placebo+Donepezil Placebo SRD: TAK-071 Placebo+Donepezil SRD: Cohort 20: TAK-071 40 mg+Donepezil SRD: Cohort 21: TAK-071 60 mg+Donepezil SRD: Cohort 22: TAK-071 80 mg+Donepezil
Arm/Group Description TAK-071 placebo-matching capsules, orally, once on Day 1 to non-Japanese healthy participants in the single-rising dose (SRD) period. TAK-071 1 mg, capsule, orally, once on Day 1 to non-Japanese healthy participants. TAK-071 3 mg capsule, orally, once on Day 1 to non-Japanese healthy participants. Dose of TAK-071 was based on the 24-hour post-dose safety, tolerability and pharmacokinetic (PK) data from cohort 1. TAK-071 9 mg capsule, orally, once on Day 1 to non-Japanese healthy participants. Dose of TAK-071 was based on 24-hour safety, tolerability, and preliminary plasma PK and 12-hour CSF PK data. TAK-071 20 mg capsule, orally, once on Day 1 to non-Japanese healthy participants. Dose of TAK-071 was based on the 24-hour post-dose safety and tolerability data from previous cohort. TAK-071 40 mg capsule, orally, once on Day 1 to non-Japanese healthy participants. Dose of TAK-071 will be based on 24-hour safety, tolerability, and preliminary plasma PK data from Cohort 4. TAK-071 80 mg capsules, orally, once on Day 1 to non-Japanese healthy participants. Dose of TAK-071 was based on 24-hour safety, tolerability, and preliminary plasma PK data from Cohort 5 TAK-071 placebo-matching capsule, orally, once on Day 1 to non-Japanese healthy participants in the multiple-rising dose (MRD) period. TAK-071 3 mg capsules, orally, once daily from Day 1 up to Day 21 to non-Japanese healthy participants. Dose of TAK-071 was based on 24-hour safety and tolerability from Cohort 4 and the 24-hour preliminary plasma PK and 12-hour CSF PK data from Cohort 3. TAK-071 9 mg capsules, orally, once daily from Day 1 up to Day 21 to non-Japanese healthy participants. Dose of TAK-071 was based on safety, tolerability and available PK data arising from the ongoing SRD part and previous MRD cohort. TAK-071 15 mg capsule, orally, once on Day 1, followed by a washout period of 7 days, then TAK-071 once daily for 21 days to non-Japanese healthy participants. Dose of TAK-071 will be based on safety, tolerability and available PK data arising from the ongoing SRD part and previous MRD cohort. TAK-071 placebo-matching capsule, orally, once daily along with donepezil 5 mg, tablets, orally, once daily from Day 1 up to Day 21 to non-Japanese healthy participants who were pre-treated with donepezil 5 mg, tablet, once daily for 3 weeks prior to administration of TAK-071. TAK-071 3 mg capsules, orally, once daily along with donepezil 5 mg, tablets, orally, once daily from Day 1 up to Day 21 to non-Japanese healthy participants who were pre-treated with donepezil 5 mg, tablet, once daily for 3 weeks prior to administration of TAK-071. Dose of TAK-071 was same as the dose used in MRD Cohort 7. TAK-071 9 mg capsules, orally, once daily along with donepezil 5 mg, tablets, orally, once daily from Day 1 up to Day 21 to non-Japanese healthy participants who were pre-treated with donepezil 5 mg, tablet, once daily for 3 weeks prior to administration of TAK-071. Dose of TAK-071 was same as the dose used in MRD Cohort 8. TAK-071 15 mg capsule, orally, once daily along with donepezil 5 mg, tablets, orally, once daily from Day 1 up to Day 21 to non-Japanese healthy participants who were pre-treated with donepezil 5 mg, tablet, once daily for 3 weeks prior to administration of TAK-071. Dose of TAK-071 was same as the dose used in MRD Cohort 9. TAK-071 placebo-matching capsule, orally, once on Day 1 to Japanese healthy participants. TAK-071 3 mg capsule, orally, once on Day 1, followed by a washout period of 7 days, then TAK-071 once daily for 21 days to Japanese healthy participants. Dose of TAK-071 was same as the dose used in MRD Cohort 7. TAK-071 9 mg capsule or matching placebo, orally, once on Day 1, followed by a washout period of 7 days, then TAK-071 once daily for 21 days to Japanese healthy participants. Dose of TAK-071 was same as the dose used in MRD Cohort 8. TAK-071 15 mg capsule, orally, once on Day 1, followed by a washout period of 7 days, then TAK-071 once daily for 21 days to Japanese healthy participants. Dose of TAK-071 was same as the dose used in MRD Cohort 9. TAK-071 10 mg capsule, orally once on Day 1 in the fasted state in Period 1 or Period 2 or Period 3 TAK-071 10 mg tablet, orally, once on Day 1 in the fasted state in Period 1 or Period 2 or Period 3 TAK-071 10 mg tablet, orally, once on Day 1 in the fed state in Period 1 or Period 2 or Period 3 TAK-071 120 mg capsule, orally, once on Day 1 to non-Japanese healthy participants. Dose of TAK-071 was based on 24-hour safety, tolerability, and preliminary plasma PK data from Cohort 6. TAK-071 160 mg capsule, orally, once on Day 1 to non-Japanese healthy participants. Dose of TAK-071 was based on 24-hour safety, tolerability, and preliminary plasma PK data from Cohort 18. TAK-071 placebo-matching capsule, orally, once on Day 1 followed by donepezil placebo-matching tablet, orally on Day 2 to non-Japanese healthy participants. TAK-071 placebo-matching capsule, orally, once on Day 1 followed by donepezil 10 mg tablet, orally, on Day 2 to non-Japanese healthy participants. TAK-071 40 mg capsule, orally, once on Day 1 followed by donepezil 10 mg, tablets, orally, once on Day 2 to non-Japanese healthy participants. Dose of TAK-071 was based on 24-hour safety, tolerability, and preliminary plasma PK data from Cohort 19. TAK-071 60 mg capsule, orally, once on Day 1 followed by donepezil 10 mg, tablets, orally, once on Day 2 to non-Japanese healthy participants. Dose of TAK-071 was based on 24-hour safety and tolerability data from Cohort 20. TAK-071 80 mg capsule, orally, once on Day 1, followed by donepezil 10 mg, tablets, orally, once on Day 2 to non-Japanese healthy participants. Dose of TAK-071 was based on 24-hour safety and tolerability data from Cohort 21.
Measure Participants 16 6 6 6 6 6 6 6 6 6 6 6 6 6 6 3 5 5 5 12 12 12 6 6 9 9 5 6 6
ECG Mean Heart Rate (HR), <50 beats/min
37.5
234.4%
33.3
555%
16.7
278.3%
16.7
278.3%
33.3
555%
33.3
555%
16.7
278.3%
33.3
555%
16.7
278.3%
33.3
555%
33.3
555%
16.7
278.3%
33.3
555%
50.0
833.3%
33.3
555%
66.7
2223.3%
40.0
800%
40.0
800%
40.0
800%
58.3
Infinity
41.7
1042.5%
33.3
832.5%
66.7
1667.5%
0
0%
44.4
740%
22.2
246.7%
60.0
666.7%
33.3
666%
50.0
833.3%
ECG Mean HR, >120 beats/min
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
20.0
400%
0
NaN
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
PR Interval, Aggregate, <=80 millisecond (msec)
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
NaN
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
PR Interval, Aggregate, >=200 msec
18.8
117.5%
0
0%
16.7
278.3%
0
0%
16.7
278.3%
16.7
278.3%
0
0%
0
0%
16.7
278.3%
0
0%
0
0%
16.7
278.3%
16.7
278.3%
16.7
278.3%
16.7
278.3%
66.7
2223.3%
0
0%
40.0
800%
20.0
400%
33.3
Infinity
25.0
625%
25.0
625%
0
0%
0
0%
11.1
185%
11.1
123.3%
20.0
222.2%
0
0%
16.7
278.3%
QRS Duration, Aggregate, <=80 msec
31.3
195.6%
33.3
555%
33.3
555%
0
0%
50.0
833.3%
16.7
278.3%
16.7
278.3%
33.3
555%
16.7
278.3%
16.7
278.3%
16.7
278.3%
50.0
833.3%
16.7
278.3%
16.7
278.3%
16.7
278.3%
33.3
1110%
40.0
800%
20.0
400%
40.0
800%
8.3
Infinity
16.7
417.5%
16.7
417.5%
16.7
417.5%
50.0
833.3%
11.1
185%
11.1
123.3%
20.0
222.2%
0
0%
16.7
278.3%
QRS Duration, Aggregate, >=180 msec
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
NaN
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
QT Interval, Aggregate, <=50 msec
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
NaN
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
QT Interval, Aggregate, >=460 msec
12.5
78.1%
33.3
555%
16.7
278.3%
0
0%
0
0%
0
0%
16.7
278.3%
0
0%
0
0%
16.7
278.3%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
20.0
400%
20.0
400%
20.0
400%
16.7
Infinity
16.7
417.5%
8.3
207.5%
16.7
417.5%
0
0%
11.1
185%
11.1
123.3%
40.0
444.4%
0
0%
0
0%
QTcB Interval, Aggregate, <=50 msec
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
NaN
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
QTcB Interval, Aggregate ≥500 OR ≥30 and ≥450 msec
0
0%
16.7
278.3%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
16.7
278.3%
16.7
278.3%
0
0%
0
0%
20.0
400%
20.0
400%
8.3
Infinity
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
20.0
222.2%
0
0%
0
0%
QTcF Interval, Aggregate, <=50 msec
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
NaN
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
QTcF Interval, Aggregate ≥500 OR ≥30 and ≥450 msec
0
0%
16.7
278.3%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
NaN
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
RR Interval, Aggregate, <=600 msec
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
16.7
278.3%
0
0%
0
0%
0
0%
20.0
400%
0
NaN
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
RR Interval, Aggregate, >=1440 msec
0
0%
16.7
278.3%
16.7
278.3%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
16.7
278.3%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
20.0
400%
20.0
400%
0
0%
0
NaN
0
0%
0
0%
16.7
417.5%
0
0%
11.1
185%
11.1
123.3%
0
0%
0
0%
0
0%
5. Primary Outcome
Title Tmax: Time of First Occurrence of Cmax for TAK-071 Single-Rising Dose (SRD) Non-Japanese Participants
Description
Time Frame Pre-dose on Day 1 and at multiple time points (up to 168 hours) post-dose

Outcome Measure Data

Analysis Population Description
Pharmacokinetic (PK) set included all participants who received study drug and had at least 1 measurable plasma concentration or amount of drug in the urine.
Arm/Group Title SRD: Cohort 1: TAK-071 1 mg SRD: Cohort 2: TAK-071 3 mg SRD: Cohort 3: TAK-071 9 mg SRD: Cohort 4: TAK-071 20 mg SRD: Cohort 5: TAK-071 40 mg SRD: Cohort 6: TAK-071 80 mg SRD: Cohort 18: TAK-071 120 mg SRD: Cohort 19: TAK-071 160 mg
Arm/Group Description TAK-071 1 mg, capsule, orally, once on Day 1 to non-Japanese healthy participants. TAK-071 3 mg capsule, orally, once on Day 1 to non-Japanese healthy participants. Dose of TAK-071 was based on the 24-hour post-dose safety, tolerability and pharmacokinetic (PK) data from cohort 1. TAK-071 9 mg capsule, orally, once on Day 1 to non-Japanese healthy participants. Dose of TAK-071 was based on 24-hour safety, tolerability, and preliminary plasma PK and 12-hour CSF PK data. TAK-071 20 mg capsule, orally, once on Day 1 to non-Japanese healthy participants. Dose of TAK-071 was based on the 24-hour post-dose safety and tolerability data from previous cohort. TAK-071 40 mg capsule, orally, once on Day 1 to non-Japanese healthy participants. Dose of TAK-071 will be based on 24-hour safety, tolerability, and preliminary plasma PK data from Cohort 4. TAK-071 80 mg capsules, orally, once on Day 1 to non-Japanese healthy participants. Dose of TAK-071 was based on 24-hour safety, tolerability, and preliminary plasma PK data from Cohort 5 TAK-071 120 mg capsule, orally, once on Day 1 to non-Japanese healthy participants. Dose of TAK-071 was based on 24-hour safety, tolerability, and preliminary plasma PK data from Cohort 6. TAK-071 160 mg capsule, orally, once on Day 1 to non-Japanese healthy participants. Dose of TAK-071 was based on 24-hour safety, tolerability, and preliminary plasma PK data from Cohort 18.
Measure Participants 6 6 6 6 6 6 6 6
Median (Full Range) [hours]
1.750
4.017
10.975
8.000
9.933
24.033
22.050
24.058
6. Primary Outcome
Title Tmax: Time of First Occurrence of Cmax for TAK-071 Multiple-Rising Dose (MRD) Non-Japanese Participants [Day 1]
Description
Time Frame Pre-dose on Day 1 and multiple time points (up to 24 hours) post-dose

Outcome Measure Data

Analysis Population Description
PK set included all participants who received study drug and had at least 1 measurable plasma concentration or amount of drug in the urine.
Arm/Group Title MRD: Cohort 7: TAK-071 3 mg MRD: Cohort 8: TAK-071 9 mg
Arm/Group Description TAK-071 3 mg capsules, orally, once daily from Day 1 up to Day 21 to non-Japanese healthy participants. Dose of TAK-071 was based on 24-hour safety and tolerability from Cohort 4 and the 24-hour preliminary plasma PK and 12-hour CSF PK data from Cohort 3. TAK-071 9 mg capsules, orally, once daily from Day 1 up to Day 21 to non-Japanese healthy participants. Dose of TAK-071 was based on safety, tolerability and available PK data arising from the ongoing SRD part and previous MRD cohort.
Measure Participants 6 6
Median (Full Range) [hours]
2.500
7.000
7. Primary Outcome
Title Tmax: Time of First Occurrence of Cmax for TAK-071 MRD Non-Japanese Participants [Day 21]
Description
Time Frame Pre-dose on Day 21 and multiple time points (up to 24 hours) post-dose

Outcome Measure Data

Analysis Population Description
PK set included all participants who received study drug and had at least 1 measurable plasma concentration or amount of drug in the urine.
Arm/Group Title MRD: Cohort 7: TAK-071 3 mg MRD: Cohort 8: TAK-071 9 mg
Arm/Group Description TAK-071 3 mg capsules, orally, once daily from Day 1 up to Day 21 to non-Japanese healthy participants. Dose of TAK-071 was based on 24-hour safety and tolerability from Cohort 4 and the 24-hour preliminary plasma PK and 12-hour CSF PK data from Cohort 3. TAK-071 9 mg capsules, orally, once daily from Day 1 up to Day 21 to non-Japanese healthy participants. Dose of TAK-071 was based on safety, tolerability and available PK data arising from the ongoing SRD part and previous MRD cohort.
Measure Participants 6 6
Median (Full Range) [hours]
2.500
4.000
8. Primary Outcome
Title Tmax: Time of First Occurrence of Cmax for TAK-071 MRD Non-Japanese Participants [Day 1]
Description
Time Frame Pre-dose on Day 1 and multiple time points (up to 96 hours) post-dose

Outcome Measure Data

Analysis Population Description
PK set included all participants who received study drug and had at least 1 measurable plasma concentration or amount of drug in the urine.
Arm/Group Title MRD: Cohort 9: TAK-071 15 mg
Arm/Group Description TAK-071 15 mg capsule, orally, once on Day 1, followed by a washout period of 7 days, then TAK-071 once daily for 21 days to non-Japanese healthy participants. Dose of TAK-071 will be based on safety, tolerability and available PK data arising from the ongoing SRD part and previous MRD cohort.
Measure Participants 6
Mean (Full Range) [hours]
24.058
9. Primary Outcome
Title Tmax: Time of First Occurrence of Cmax for TAK-071 MRD Non-Japanese Participants [Day 8]
Description
Time Frame Pre-dose on Day 8 and multiple time points (up to 24 hour) post-dose

Outcome Measure Data

Analysis Population Description
PK set included all participants who received study drug and had at least 1 measurable plasma concentration or amount of drug in the urine.
Arm/Group Title MRD: Cohort 9: TAK-071 15 mg
Arm/Group Description TAK-071 15 mg capsule, orally, once on Day 1, followed by a washout period of 7 days, then TAK-071 once daily for 21 days to non-Japanese healthy participants. Dose of TAK-071 will be based on safety, tolerability and available PK data arising from the ongoing SRD part and previous MRD cohort.
Measure Participants 6
Median (Full Range) [hours]
11.017
10. Primary Outcome
Title Tmax: Time of First Occurrence of Cmax for TAK-071 MRD Non-Japanese Participants [Day 28]
Description
Time Frame Pre-dose on Day 28 and multiple time points (up to 36 hours) post-dose

Outcome Measure Data

Analysis Population Description
PK set included all participants who received study drug and had at least 1 measurable plasma concentration or amount of drug in the urine.
Arm/Group Title MRD: Cohort 9: TAK-071 15 mg
Arm/Group Description TAK-071 15 mg capsule, orally, once on Day 1, followed by a washout period of 7 days, then TAK-071 once daily for 21 days to non-Japanese healthy participants. Dose of TAK-071 will be based on safety, tolerability and available PK data arising from the ongoing SRD part and previous MRD cohort.
Measure Participants 6
Mean (Full Range) [hours]
3.000
11. Primary Outcome
Title Tmax: Time of First Occurrence of Cmax for TAK-071 MRD Japanese Participants [Day 1]
Description
Time Frame Pre-dose on Day 1 and multiple time points (up to 96 hours) post-dose

Outcome Measure Data

Analysis Population Description
PK set included all participants who received study drug and had at least 1 measurable plasma concentration or amount of drug in the urine.
Arm/Group Title MRD: Cohort 13: TAK-071 3 mg MRD: Cohort 14: TAK-071 9 mg MRD: Cohort 15: TAK-071 15 mg
Arm/Group Description TAK-071 3 mg capsule, orally, once on Day 1, followed by a washout period of 7 days, then TAK-071 once daily for 21 days to Japanese healthy participants. Dose of TAK-071 was same as the dose used in MRD Cohort 7. TAK-071 9 mg capsule or matching placebo, orally, once on Day 1, followed by a washout period of 7 days, then TAK-071 once daily for 21 days to Japanese healthy participants. Dose of TAK-071 was same as the dose used in MRD Cohort 8. TAK-071 15 mg capsule, orally, once on Day 1, followed by a washout period of 7 days, then TAK-071 once daily for 21 days to Japanese healthy participants. Dose of TAK-071 was same as the dose used in MRD Cohort 9.
Measure Participants 5 5 5
Median (Full Range) [hours]
4.000
6.000
12.000
12. Primary Outcome
Title Tmax: Time of First Occurrence of Cmax for TAK-071 MRD Japanese Participants [Day 8]
Description
Time Frame Pre-dose on Day 8 and multiple time points (up to 24 hours) post-dose

Outcome Measure Data

Analysis Population Description
PK set included all participants who received study drug and had at least 1 measurable plasma concentration or amount of drug in the urine.
Arm/Group Title MRD: Cohort 13: TAK-071 3 mg MRD: Cohort 14: TAK-071 9 mg MRD: Cohort 15: TAK-071 15 mg
Arm/Group Description TAK-071 3 mg capsule, orally, once on Day 1, followed by a washout period of 7 days, then TAK-071 once daily for 21 days to Japanese healthy participants. Dose of TAK-071 was same as the dose used in MRD Cohort 7. TAK-071 9 mg capsule or matching placebo, orally, once on Day 1, followed by a washout period of 7 days, then TAK-071 once daily for 21 days to Japanese healthy participants. Dose of TAK-071 was same as the dose used in MRD Cohort 8. TAK-071 15 mg capsule, orally, once on Day 1, followed by a washout period of 7 days, then TAK-071 once daily for 21 days to Japanese healthy participants. Dose of TAK-071 was same as the dose used in MRD Cohort 9.
Measure Participants 5 5 5
Median (Full Range) [hours]
4.000
6.000
8.000
13. Primary Outcome
Title Tmax: Time of First Occurrence of Cmax for TAK-071 MRD Japanese Participants [Day 28]
Description
Time Frame Pre-dose on Day 28 and multiple time points (up to 24 hours) post-dose

Outcome Measure Data

Analysis Population Description
PK set included all participants who received study drug and had at least 1 measurable plasma concentration or amount of drug in the urine.
Arm/Group Title MRD: Cohort 13: TAK-071 3 mg MRD: Cohort 14: TAK-071 9 mg MRD: Cohort 15: TAK-071 15 mg
Arm/Group Description TAK-071 3 mg capsule, orally, once on Day 1, followed by a washout period of 7 days, then TAK-071 once daily for 21 days to Japanese healthy participants. Dose of TAK-071 was same as the dose used in MRD Cohort 7. TAK-071 9 mg capsule or matching placebo, orally, once on Day 1, followed by a washout period of 7 days, then TAK-071 once daily for 21 days to Japanese healthy participants. Dose of TAK-071 was same as the dose used in MRD Cohort 8. TAK-071 15 mg capsule, orally, once on Day 1, followed by a washout period of 7 days, then TAK-071 once daily for 21 days to Japanese healthy participants. Dose of TAK-071 was same as the dose used in MRD Cohort 9.
Measure Participants 5 5 5
Median (Full Range) [hours]
4.000
3.000
3.000
14. Primary Outcome
Title Tmax: Time of First Occurrence of Cmax for TAK-071 MRD Non-Japanese Participants [Day 1]
Description
Time Frame Pre-dose on Day 1 and multiple time points (up to 24 hours) post-dose

Outcome Measure Data

Analysis Population Description
PK set included all participants who received study drug and had at least 1 measurable plasma concentration or amount of drug in the urine.
Arm/Group Title MRD: Cohort 10: TAK-071 3 mg+Donepezil 5 mg MRD: Cohort 11: TAK-071 9 mg + Donepezil 5 mg MRD: Cohort 12: TAK-071 15 mg+Donepezil 5 mg
Arm/Group Description TAK-071 3 mg capsules, orally, once daily along with donepezil 5 mg, tablets, orally, once daily from Day 1 up to Day 21 to non-Japanese healthy participants who were pre-treated with donepezil 5 mg, tablet, once daily for 3 weeks prior to administration of TAK-071. Dose of TAK-071 was same as the dose used in MRD Cohort 7. TAK-071 9 mg capsules, orally, once daily along with donepezil 5 mg, tablets, orally, once daily from Day 1 up to Day 21 to non-Japanese healthy participants who were pre-treated with donepezil 5 mg, tablet, once daily for 3 weeks prior to administration of TAK-071. Dose of TAK-071 was same as the dose used in MRD Cohort 8. TAK-071 15 mg capsule, orally, once daily along with donepezil 5 mg, tablets, orally, once daily from Day 1 up to Day 21 to non-Japanese healthy participants who were pre-treated with donepezil 5 mg, tablet, once daily for 3 weeks prior to administration of TAK-071. Dose of TAK-071 was same as the dose used in MRD Cohort 9.
Measure Participants 6 6 6
Median (Full Range) [hours]
3.508
4.992
7.000
15. Primary Outcome
Title Tmax: Time of First Occurrence of Cmax for TAK-071 MRD Non-Japanese Participants [Day 21]
Description
Time Frame Pre-dose on Day 21 and multiple time points (up to 24 hours) post-dose

Outcome Measure Data

Analysis Population Description
PK set included all participants who received study drug and had at least 1 measurable plasma concentration or amount of drug in the urine.
Arm/Group Title MRD: Cohort 10: TAK-071 3 mg+Donepezil 5 mg MRD: Cohort 11: TAK-071 9 mg + Donepezil 5 mg MRD: Cohort 12: TAK-071 15 mg+Donepezil 5 mg
Arm/Group Description TAK-071 3 mg capsules, orally, once daily along with donepezil 5 mg, tablets, orally, once daily from Day 1 up to Day 21 to non-Japanese healthy participants who were pre-treated with donepezil 5 mg, tablet, once daily for 3 weeks prior to administration of TAK-071. Dose of TAK-071 was same as the dose used in MRD Cohort 7. TAK-071 9 mg capsules, orally, once daily along with donepezil 5 mg, tablets, orally, once daily from Day 1 up to Day 21 to non-Japanese healthy participants who were pre-treated with donepezil 5 mg, tablet, once daily for 3 weeks prior to administration of TAK-071. Dose of TAK-071 was same as the dose used in MRD Cohort 8. TAK-071 15 mg capsule, orally, once daily along with donepezil 5 mg, tablets, orally, once daily from Day 1 up to Day 21 to non-Japanese healthy participants who were pre-treated with donepezil 5 mg, tablet, once daily for 3 weeks prior to administration of TAK-071. Dose of TAK-071 was same as the dose used in MRD Cohort 9.
Measure Participants 6 6 6
Median (Full Range) [hours]
3.500
3.008
3.500
16. Primary Outcome
Title Tmax: Time of First Occurrence of Cmax for TAK-071 Relative Bioavailability and Food Effect
Description
Time Frame Pre-dose on Day 21 and multiple time points (up to 168 hours) post-dose

Outcome Measure Data

Analysis Population Description
PK set included all participants who received study drug and had at least 1 measurable plasma concentration or amount of drug in the urine.
Arm/Group Title Bioavailability (BA)/Food Effect: Cohort 17 Regimen A BA/Food Effect: Cohort 17 Regimen B BA/Food Effect: Cohort 17 Regimen C
Arm/Group Description TAK-071 10 mg capsule, orally once on Day 1 in the fasted state in Period 1 or Period 2 or Period 3 TAK-071 10 mg tablet, orally, once on Day 1 in the fasted state in Period 1 or Period 2 or Period 3 TAK-071 10 mg tablet, orally, once on Day 1 in the fed state in Period 1 or Period 2 or Period 3
Measure Participants 12 12 12
Median (Full Range) [hours]
4.983
2.000
6.000
17. Primary Outcome
Title Tmax: Time of First Occurrence of Cmax for TAK-071 SRD Non-Japanese Participants TAK-071+Donepezil
Description
Time Frame Pre-dose on Day 1 and at multiple time points (up to 168 hours) post-dose

Outcome Measure Data

Analysis Population Description
PK set included all participants who received study drug and had at least 1 measurable plasma concentration or amount of drug in the urine.
Arm/Group Title SRD: Cohort 20: TAK-071 40 mg+Donepezil SRD: Cohort 21: TAK-071 60 mg+Donepezil SRD: Cohort 22: TAK-071 80 mg+Donepezil
Arm/Group Description TAK-071 40 mg capsule, orally, once on Day 1 followed by donepezil 10 mg, tablets, orally, once on Day 2 to non-Japanese healthy participants. Dose of TAK-071 was based on 24-hour safety, tolerability, and preliminary plasma PK data from Cohort 19. TAK-071 60 mg capsule, orally, once on Day 1 followed by donepezil 10 mg, tablets, orally, once on Day 2 to non-Japanese healthy participants. Dose of TAK-071 was based on 24-hour safety and tolerability data from Cohort 20. TAK-071 80 mg capsule, orally, once on Day 1, followed by donepezil 10 mg, tablets, orally, once on Day 2 to non-Japanese healthy participants. Dose of TAK-071 was based on 24-hour safety and tolerability data from Cohort 21.
Measure Participants 3 6 5
Median (Full Range) [hours]
26.000
26.000
30.000
18. Primary Outcome
Title Cmax: Maximum Observed Plasma Concentration for TAK-071 Single-Rising Dose (SRD) Non-Japanese Participants
Description
Time Frame Pre-dose on Day 1 and at multiple time points (up to 168 hours) post-dose

Outcome Measure Data

Analysis Population Description
PK set included all participants who received study drug and had at least 1 measurable plasma concentration or amount of drug in the urine.
Arm/Group Title SRD: Cohort 1: TAK-071 1 mg SRD: Cohort 2: TAK-071 3 mg SRD: Cohort 3: TAK-071 9 mg SRD: Cohort 4: TAK-071 20 mg SRD: Cohort 5: TAK-071 40 mg SRD: Cohort 6: TAK-071 80 mg SRD: Cohort 18: TAK-071 120 mg SRD: Cohort 19: TAK-071 160 mg
Arm/Group Description TAK-071 1 mg, capsule, orally, once on Day 1 to non-Japanese healthy participants. TAK-071 3 mg capsule, orally, once on Day 1 to non-Japanese healthy participants. Dose of TAK-071 was based on the 24-hour post-dose safety, tolerability and pharmacokinetic (PK) data from cohort 1. TAK-071 9 mg capsule, orally, once on Day 1 to non-Japanese healthy participants. Dose of TAK-071 was based on 24-hour safety, tolerability, and preliminary plasma PK and 12-hour CSF PK data. TAK-071 20 mg capsule, orally, once on Day 1 to non-Japanese healthy participants. Dose of TAK-071 was based on the 24-hour post-dose safety and tolerability data from previous cohort. TAK-071 40 mg capsule, orally, once on Day 1 to non-Japanese healthy participants. Dose of TAK-071 will be based on 24-hour safety, tolerability, and preliminary plasma PK data from Cohort 4. TAK-071 80 mg capsules, orally, once on Day 1 to non-Japanese healthy participants. Dose of TAK-071 was based on 24-hour safety, tolerability, and preliminary plasma PK data from Cohort 5 TAK-071 120 mg capsule, orally, once on Day 1 to non-Japanese healthy participants. Dose of TAK-071 was based on 24-hour safety, tolerability, and preliminary plasma PK data from Cohort 6. TAK-071 160 mg capsule, orally, once on Day 1 to non-Japanese healthy participants. Dose of TAK-071 was based on 24-hour safety, tolerability, and preliminary plasma PK data from Cohort 18.
Measure Participants 6 6 6 6 6 6 6 6
Mean (Standard Deviation) [ng/mL]
25.65
(5.8589)
65.82
(5.4268)
162.2
(36.548)
328.0
(72.200)
485.7
(240.47)
901.7
(210.05)
1292
(315.30)
1387
(312.13)
19. Primary Outcome
Title Cmax: Maximum Observed Plasma Concentration for TAK-071 Multiple-Rising Dose (MRD) Non-Japanese Participants [Day 1]
Description
Time Frame Pre-dose on Day 1 and multiple time points (up to 24 hours) post-dose

Outcome Measure Data

Analysis Population Description
PK set included all participants who received study drug and had at least 1 measurable plasma concentration or amount of drug in the urine.
Arm/Group Title MRD: Cohort 7: TAK-071 3 mg MRD: Cohort 8: TAK-071 9 mg
Arm/Group Description TAK-071 3 mg capsules, orally, once daily from Day 1 up to Day 21 to non-Japanese healthy participants. Dose of TAK-071 was based on 24-hour safety and tolerability from Cohort 4 and the 24-hour preliminary plasma PK and 12-hour CSF PK data from Cohort 3. TAK-071 9 mg capsules, orally, once daily from Day 1 up to Day 21 to non-Japanese healthy participants. Dose of TAK-071 was based on safety, tolerability and available PK data arising from the ongoing SRD part and previous MRD cohort.
Measure Participants 6 6
Mean (Standard Deviation) [ng/mL]
74.33
(18.186)
196.2
(54.668)
20. Primary Outcome
Title Cmax: Maximum Observed Plasma Concentration for TAK-071 MRD Non-Japanese Participants [Day 21]
Description
Time Frame Pre-dose on Day 21 and multiple time points (up to 24 hours) post-dose

Outcome Measure Data

Analysis Population Description
PK set included all participants who received study drug and had at least 1 measurable plasma concentration or amount of drug in the urine.
Arm/Group Title MRD: Cohort 7: TAK-071 3 mg MRD: Cohort 8: TAK-071 9 mg
Arm/Group Description TAK-071 3 mg capsules, orally, once daily from Day 1 up to Day 21 to non-Japanese healthy participants. Dose of TAK-071 was based on 24-hour safety and tolerability from Cohort 4 and the 24-hour preliminary plasma PK and 12-hour CSF PK data from Cohort 3. TAK-071 9 mg capsules, orally, once daily from Day 1 up to Day 21 to non-Japanese healthy participants. Dose of TAK-071 was based on safety, tolerability and available PK data arising from the ongoing SRD part and previous MRD cohort.
Measure Participants 6 6
Mean (Standard Deviation) [ng/mL]
244.5
(66.163)
646.5
(95.032)
21. Primary Outcome
Title Cmax: Maximum Observed Plasma Concentration for TAK-071 MRD Non-Japanese Participants [Day 1]
Description
Time Frame Pre-dose on Day 1 and multiple time points (up to 96 hours) post-dose

Outcome Measure Data

Analysis Population Description
PK set included all participants who received study drug and had at least 1 measurable plasma concentration or amount of drug in the urine.
Arm/Group Title MRD: Cohort 9: TAK-071 15 mg
Arm/Group Description TAK-071 15 mg capsule, orally, once on Day 1, followed by a washout period of 7 days, then TAK-071 once daily for 21 days to non-Japanese healthy participants. Dose of TAK-071 will be based on safety, tolerability and available PK data arising from the ongoing SRD part and previous MRD cohort.
Measure Participants 6
Mean (Standard Deviation) [ng/mL]
264.8
(70.516)
22. Primary Outcome
Title Cmax: Maximum Observed Plasma Concentration for TAK-071 MRD Non-Japanese Participants [Day 8]
Description
Time Frame Pre-dose on Day 8 and multiple time points (up to 24 hour) post-dose

Outcome Measure Data

Analysis Population Description
PK set included all participants who received study drug and had at least 1 measurable plasma concentration or amount of drug in the urine.
Arm/Group Title MRD: Cohort 9: TAK-071 15 mg
Arm/Group Description TAK-071 15 mg capsule, orally, once on Day 1, followed by a washout period of 7 days, then TAK-071 once daily for 21 days to non-Japanese healthy participants. Dose of TAK-071 will be based on safety, tolerability and available PK data arising from the ongoing SRD part and previous MRD cohort.
Measure Participants 6
Mean (Standard Deviation) [ng/mL]
294.2
(57.007)
23. Primary Outcome
Title Cmax: Maximum Observed Plasma Concentration for TAK-071 MRD Non-Japanese Participants [Day 28]
Description
Time Frame Pre-dose on Day 28 and multiple time points (up to 36 hours) post-dose

Outcome Measure Data

Analysis Population Description
PK set included all participants who received study drug and had at least 1 measurable plasma concentration or amount of drug in the urine.
Arm/Group Title MRD: Cohort 9: TAK-071 15 mg
Arm/Group Description TAK-071 15 mg capsule, orally, once on Day 1, followed by a washout period of 7 days, then TAK-071 once daily for 21 days to non-Japanese healthy participants. Dose of TAK-071 will be based on safety, tolerability and available PK data arising from the ongoing SRD part and previous MRD cohort.
Measure Participants 5
Mean (Standard Deviation) [ng/mL]
936.4
(173.98)
24. Primary Outcome
Title Cmax: Maximum Observed Plasma Concentration for TAK-071 MRD Japanese Participants [Day 1]
Description
Time Frame Pre-dose on Day 1 and multiple time points (up to 96 hours) post-dose

Outcome Measure Data

Analysis Population Description
PK set included all participants who received study drug and had at least 1 measurable plasma concentration or amount of drug in the urine.
Arm/Group Title MRD: Cohort 13: TAK-071 3 mg MRD: Cohort 14: TAK-071 9 mg MRD: Cohort 15: TAK-071 15 mg
Arm/Group Description TAK-071 3 mg capsule, orally, once on Day 1, followed by a washout period of 7 days, then TAK-071 once daily for 21 days to Japanese healthy participants. Dose of TAK-071 was same as the dose used in MRD Cohort 7. TAK-071 9 mg capsule or matching placebo, orally, once on Day 1, followed by a washout period of 7 days, then TAK-071 once daily for 21 days to Japanese healthy participants. Dose of TAK-071 was same as the dose used in MRD Cohort 8. TAK-071 15 mg capsule, orally, once on Day 1, followed by a washout period of 7 days, then TAK-071 once daily for 21 days to Japanese healthy participants. Dose of TAK-071 was same as the dose used in MRD Cohort 9.
Measure Participants 5 5 5
Mean (Standard Deviation) [ng/mL]
78.98
(10.736)
208.4
(47.773)
278.0
(63.828)
25. Primary Outcome
Title Cmax: Maximum Observed Plasma Concentration for TAK-071 MRD Japanese Participants [Day 8]
Description
Time Frame Pre-dose on Day 8 and multiple time points (up to 24 hours) post-dose

Outcome Measure Data

Analysis Population Description
PK set included all participants who received study drug and had at least 1 measurable plasma concentration or amount of drug in the urine.
Arm/Group Title MRD: Cohort 13: TAK-071 3 mg MRD: Cohort 14: TAK-071 9 mg MRD: Cohort 15: TAK-071 15 mg
Arm/Group Description TAK-071 3 mg capsule, orally, once on Day 1, followed by a washout period of 7 days, then TAK-071 once daily for 21 days to Japanese healthy participants. Dose of TAK-071 was same as the dose used in MRD Cohort 7. TAK-071 9 mg capsule or matching placebo, orally, once on Day 1, followed by a washout period of 7 days, then TAK-071 once daily for 21 days to Japanese healthy participants. Dose of TAK-071 was same as the dose used in MRD Cohort 8. TAK-071 15 mg capsule, orally, once on Day 1, followed by a washout period of 7 days, then TAK-071 once daily for 21 days to Japanese healthy participants. Dose of TAK-071 was same as the dose used in MRD Cohort 9.
Measure Participants 5 5 5
Mean (Standard Deviation) [ng/mL]
81.16
(17.379)
235.4
(37.740)
329.6
(99.889)
26. Primary Outcome
Title Cmax: Maximum Observed Plasma Concentration for TAK-071 MRD Japanese Participants [Day 28]
Description
Time Frame Pre-dose on Day 28 and multiple time points (up to 24 hours) post-dose

Outcome Measure Data

Analysis Population Description
PK set included all participants who received study drug and had at least 1 measurable plasma concentration or amount of drug in the urine.
Arm/Group Title MRD: Cohort 13: TAK-071 3 mg MRD: Cohort 14: TAK-071 9 mg MRD: Cohort 15: TAK-071 15 mg
Arm/Group Description TAK-071 3 mg capsule, orally, once on Day 1, followed by a washout period of 7 days, then TAK-071 once daily for 21 days to Japanese healthy participants. Dose of TAK-071 was same as the dose used in MRD Cohort 7. TAK-071 9 mg capsule or matching placebo, orally, once on Day 1, followed by a washout period of 7 days, then TAK-071 once daily for 21 days to Japanese healthy participants. Dose of TAK-071 was same as the dose used in MRD Cohort 8. TAK-071 15 mg capsule, orally, once on Day 1, followed by a washout period of 7 days, then TAK-071 once daily for 21 days to Japanese healthy participants. Dose of TAK-071 was same as the dose used in MRD Cohort 9.
Measure Participants 5 5 5
Mean (Standard Deviation) [ng/mL]
235.6
(49.242)
680.2
(181.99)
895.2
(420.14)
27. Primary Outcome
Title Cmax: Maximum Observed Plasma Concentration for TAK-071 MRD Non-Japanese Participants [Day 1]
Description
Time Frame Pre-dose on Day 1 and multiple time points (up to 24 hours) post-dose

Outcome Measure Data

Analysis Population Description
PK set included all participants who received study drug and had at least 1 measurable plasma concentration or amount of drug in the urine.
Arm/Group Title MRD: Cohort 10: TAK-071 3 mg+Donepezil 5 mg MRD: Cohort 11: TAK-071 9 mg + Donepezil 5 mg MRD: Cohort 12: TAK-071 15 mg+Donepezil 5 mg
Arm/Group Description TAK-071 3 mg capsules, orally, once daily along with donepezil 5 mg, tablets, orally, once daily from Day 1 up to Day 21 to non-Japanese healthy participants who were pre-treated with donepezil 5 mg, tablet, once daily for 3 weeks prior to administration of TAK-071. Dose of TAK-071 was same as the dose used in MRD Cohort 7. TAK-071 9 mg capsules, orally, once daily along with donepezil 5 mg, tablets, orally, once daily from Day 1 up to Day 21 to non-Japanese healthy participants who were pre-treated with donepezil 5 mg, tablet, once daily for 3 weeks prior to administration of TAK-071. Dose of TAK-071 was same as the dose used in MRD Cohort 8. TAK-071 15 mg capsule, orally, once daily along with donepezil 5 mg, tablets, orally, once daily from Day 1 up to Day 21 to non-Japanese healthy participants who were pre-treated with donepezil 5 mg, tablet, once daily for 3 weeks prior to administration of TAK-071. Dose of TAK-071 was same as the dose used in MRD Cohort 9.
Measure Participants 6 6 6
Mean (Standard Deviation) [ng/mL]
79.12
(12.954)
194.2
(17.325)
303.7
(32.371)
28. Primary Outcome
Title Cmax: Maximum Observed Plasma Concentration for TAK-071 MRD Non-Japanese Participants [Day 21]
Description
Time Frame Pre-dose on Day 21 and multiple time points (up to 24 hours) post-dose

Outcome Measure Data

Analysis Population Description
PK set included all participants who received study drug and had at least 1 measurable plasma concentration or amount of drug in the urine.
Arm/Group Title MRD: Cohort 10: TAK-071 3 mg+Donepezil 5 mg MRD: Cohort 11: TAK-071 9 mg + Donepezil 5 mg MRD: Cohort 12: TAK-071 15 mg+Donepezil 5 mg
Arm/Group Description TAK-071 3 mg capsules, orally, once daily along with donepezil 5 mg, tablets, orally, once daily from Day 1 up to Day 21 to non-Japanese healthy participants who were pre-treated with donepezil 5 mg, tablet, once daily for 3 weeks prior to administration of TAK-071. Dose of TAK-071 was same as the dose used in MRD Cohort 7. TAK-071 9 mg capsules, orally, once daily along with donepezil 5 mg, tablets, orally, once daily from Day 1 up to Day 21 to non-Japanese healthy participants who were pre-treated with donepezil 5 mg, tablet, once daily for 3 weeks prior to administration of TAK-071. Dose of TAK-071 was same as the dose used in MRD Cohort 8. TAK-071 15 mg capsule, orally, once daily along with donepezil 5 mg, tablets, orally, once daily from Day 1 up to Day 21 to non-Japanese healthy participants who were pre-treated with donepezil 5 mg, tablet, once daily for 3 weeks prior to administration of TAK-071. Dose of TAK-071 was same as the dose used in MRD Cohort 9.
Measure Participants 6 6 6
Mean (Standard Deviation) [ng/mL]
232.8
(69.277)
678.0
(67.620)
970.7
(228.98)
29. Primary Outcome
Title Cmax: Maximum Observed Plasma Concentration for TAK-071 Relative Bioavailability and Food Effect
Description
Time Frame Pre-dose on Day 1 and multiple time points (up to 168 hours) post-dose

Outcome Measure Data

Analysis Population Description
PK set included all participants who received study drug and had at least 1 measurable plasma concentration or amount of drug in the urine.
Arm/Group Title Bioavailability (BA)/Food Effect: Cohort 17 Regimen A BA/Food Effect: Cohort 17 Regimen B BA/Food Effect: Cohort 17 Regimen C
Arm/Group Description TAK-071 10 mg capsule, orally once on Day 1 in the fasted state in Period 1 or Period 2 or Period 3 TAK-071 10 mg tablet, orally, once on Day 1 in the fasted state in Period 1 or Period 2 or Period 3 TAK-071 10 mg tablet, orally, once on Day 1 in the fed state in Period 1 or Period 2 or Period 3
Measure Participants 12 12 12
Mean (Standard Deviation) [ng/mL]
219.7
(46.986)
251.0
(41.946)
242.5
(41.513)
30. Primary Outcome
Title Cmax: Maximum Observed Plasma Concentration for TAK-071 SRD Non-Japanese Participants TAK-071+Donepezil
Description
Time Frame Pre-dose on Day 1 and at multiple time points (up to 168 hours) post-dose

Outcome Measure Data

Analysis Population Description
PK set included all participants who received study drug and had at least 1 measurable plasma concentration or amount of drug in the urine.
Arm/Group Title SRD: Cohort 20: TAK-071 40 mg+Donepezil SRD: Cohort 21: TAK-071 60 mg+Donepezil SRD: Cohort 22: TAK-071 80 mg+Donepezil
Arm/Group Description TAK-071 40 mg capsule, orally, once on Day 1 followed by donepezil 10 mg, tablets, orally, once on Day 2 to non-Japanese healthy participants. Dose of TAK-071 was based on 24-hour safety, tolerability, and preliminary plasma PK data from Cohort 19. TAK-071 60 mg capsule, orally, once on Day 1 followed by donepezil 10 mg, tablets, orally, once on Day 2 to non-Japanese healthy participants. Dose of TAK-071 was based on 24-hour safety and tolerability data from Cohort 20. TAK-071 80 mg capsule, orally, once on Day 1, followed by donepezil 10 mg, tablets, orally, once on Day 2 to non-Japanese healthy participants. Dose of TAK-071 was based on 24-hour safety and tolerability data from Cohort 21.
Measure Participants 3 6 5
Mean (Standard Deviation) [ng/mL]
1110
(85.440)
725.8
(186.03)
532.2
(28.508)
31. Primary Outcome
Title AUC(0-24): Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours for TAK-071 Single-Rising Dose (SRD) Non-Japanese Participants
Description
Time Frame Pre-dose on Day 1 and at multiple time points (up to 168 hours) post-dose

Outcome Measure Data

Analysis Population Description
PK set included all participants who received study drug and had at least 1 measurable plasma concentration or amount of drug in the urine.
Arm/Group Title SRD: Cohort 1: TAK-071 1 mg SRD: Cohort 2: TAK-071 3 mg SRD: Cohort 3: TAK-071 9 mg SRD: Cohort 4: TAK-071 20 mg SRD: Cohort 5: TAK-071 40 mg SRD: Cohort 6: TAK-071 80 mg SRD: Cohort 18: TAK-071 120 mg SRD: Cohort 19: TAK-071 160 mg
Arm/Group Description TAK-071 1 mg, capsule, orally, once on Day 1 to non-Japanese healthy participants. TAK-071 3 mg capsule, orally, once on Day 1 to non-Japanese healthy participants. Dose of TAK-071 was based on the 24-hour post-dose safety, tolerability and pharmacokinetic (PK) data from cohort 1. TAK-071 9 mg capsule, orally, once on Day 1 to non-Japanese healthy participants. Dose of TAK-071 was based on 24-hour safety, tolerability, and preliminary plasma PK and 12-hour CSF PK data. TAK-071 20 mg capsule, orally, once on Day 1 to non-Japanese healthy participants. Dose of TAK-071 was based on the 24-hour post-dose safety and tolerability data from previous cohort. TAK-071 40 mg capsule, orally, once on Day 1 to non-Japanese healthy participants. Dose of TAK-071 will be based on 24-hour safety, tolerability, and preliminary plasma PK data from Cohort 4. TAK-071 80 mg capsules, orally, once on Day 1 to non-Japanese healthy participants. Dose of TAK-071 was based on 24-hour safety, tolerability, and preliminary plasma PK data from Cohort 5 TAK-071 120 mg capsule, orally, once on Day 1 to non-Japanese healthy participants. Dose of TAK-071 was based on 24-hour safety, tolerability, and preliminary plasma PK data from Cohort 6. TAK-071 160 mg capsule, orally, once on Day 1 to non-Japanese healthy participants. Dose of TAK-071 was based on 24-hour safety, tolerability, and preliminary plasma PK data from Cohort 18.
Measure Participants 6 6 6 6 6 6 6 6
Mean (Standard Deviation) [h*ng/mL]
459.3
(111.88)
1197
(92.810)
3257
(634.89)
6383
(1162.4)
8905
(4529.9)
16300
(3468.9)
22350
(7203.2)
25660
(8297.7)
32. Primary Outcome
Title AUC(0-24): Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours for TAK-071 Multiple-Rising Dose (MRD) Non-Japanese Participants [Day 1]
Description
Time Frame Pre-dose on Day 1 and multiple time points (up to 24 hours) post-dose

Outcome Measure Data

Analysis Population Description
PK set included all participants who received study drug and had at least 1 measurable plasma concentration or amount of drug in the urine.
Arm/Group Title MRD: Cohort 7: TAK-071 3 mg MRD: Cohort 8: TAK-071 9 mg
Arm/Group Description TAK-071 3 mg capsules, orally, once daily from Day 1 up to Day 21 to non-Japanese healthy participants. Dose of TAK-071 was based on 24-hour safety and tolerability from Cohort 4 and the 24-hour preliminary plasma PK and 12-hour CSF PK data from Cohort 3. TAK-071 9 mg capsules, orally, once daily from Day 1 up to Day 21 to non-Japanese healthy participants. Dose of TAK-071 was based on safety, tolerability and available PK data arising from the ongoing SRD part and previous MRD cohort.
Measure Participants 6 6
Mean (Standard Deviation) [h*ng/mL]
1347
(302.98)
3550
(765.01)
33. Primary Outcome
Title AUC(0-24): Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours for TAK-071 MRD Non-Japanese Participants [Day 21]
Description
Time Frame Pre-dose on Day 21 and multiple time points (up to 24 hours) post-dose

Outcome Measure Data

Analysis Population Description
PK set included all participants who received study drug and had at least 1 measurable plasma concentration or amount of drug in the urine.
Arm/Group Title MRD: Cohort 7: TAK-071 3 mg MRD: Cohort 8: TAK-071 9 mg
Arm/Group Description TAK-071 3 mg capsules, orally, once daily from Day 1 up to Day 21 to non-Japanese healthy participants. Dose of TAK-071 was based on 24-hour safety and tolerability from Cohort 4 and the 24-hour preliminary plasma PK and 12-hour CSF PK data from Cohort 3. TAK-071 9 mg capsules, orally, once daily from Day 1 up to Day 21 to non-Japanese healthy participants. Dose of TAK-071 was based on safety, tolerability and available PK data arising from the ongoing SRD part and previous MRD cohort.
Measure Participants 6 6
Mean (Standard Deviation) [h*ng/mL]
4783
(1258.0)
12520
(2132.7)
34. Primary Outcome
Title AUC(0-24): Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours for TAK-071 MRD Non-Japanese Participants [Day 1]
Description
Time Frame Pre-dose on Day 1 and multiple time points (up to 96 hours) post-dose

Outcome Measure Data

Analysis Population Description
PK set included all participants who received study drug and had at least 1 measurable plasma concentration or amount of drug in the urine.
Arm/Group Title MRD: Cohort 9: TAK-071 15 mg
Arm/Group Description TAK-071 15 mg capsule, orally, once on Day 1, followed by a washout period of 7 days, then TAK-071 once daily for 21 days to non-Japanese healthy participants. Dose of TAK-071 will be based on safety, tolerability and available PK data arising from the ongoing SRD part and previous MRD cohort.
Measure Participants 6
Mean (Standard Deviation) [h*ng/mL]
5332
(1688.9)
35. Primary Outcome
Title AUC(0-24): Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours for TAK-071 MRD Non-Japanese Participants [Day 8]
Description
Time Frame Pre-dose on Day 8 and multiple time points (up to 24 hour) post-dose

Outcome Measure Data

Analysis Population Description
PK set included all participants who received study drug and had at least 1 measurable plasma concentration or amount of drug in the urine.
Arm/Group Title MRD: Cohort 9: TAK-071 15 mg
Arm/Group Description TAK-071 15 mg capsule, orally, once on Day 1, followed by a washout period of 7 days, then TAK-071 once daily for 21 days to non-Japanese healthy participants. Dose of TAK-071 will be based on safety, tolerability and available PK data arising from the ongoing SRD part and previous MRD cohort.
Measure Participants 6
Mean (Standard Deviation) [h*ng/mL]
5831
(998.50)
36. Primary Outcome
Title AUC(0-24): Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours for TAK-071 MRD Non-Japanese Participants [Day 28]
Description
Time Frame Pre-dose on Day 28 and multiple time points (up to 36 hours) post-dose

Outcome Measure Data

Analysis Population Description
PK set included all participants who received study drug and had at least 1 measurable plasma concentration or amount of drug in the urine.
Arm/Group Title MRD: Cohort 9: TAK-071 15 mg
Arm/Group Description TAK-071 15 mg capsule, orally, once on Day 1, followed by a washout period of 7 days, then TAK-071 once daily for 21 days to non-Japanese healthy participants. Dose of TAK-071 will be based on safety, tolerability and available PK data arising from the ongoing SRD part and previous MRD cohort.
Measure Participants 5
Mean (Standard Deviation) [h*ng/mL]
19920
(4563.7)
37. Primary Outcome
Title AUC(0-24): Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours for TAK-071 MRD Japanese Participants [Day 1]
Description
Time Frame Pre-dose on Day 1 and multiple time points (up to 96 hours) post-dose

Outcome Measure Data

Analysis Population Description
PK set included all participants who received study drug and had at least 1 measurable plasma concentration or amount of drug in the urine.
Arm/Group Title MRD: Cohort 13: TAK-071 3 mg MRD: Cohort 14: TAK-071 9 mg MRD: Cohort 15: TAK-071 15 mg
Arm/Group Description TAK-071 3 mg capsule, orally, once on Day 1, followed by a washout period of 7 days, then TAK-071 once daily for 21 days to Japanese healthy participants. Dose of TAK-071 was same as the dose used in MRD Cohort 7. TAK-071 9 mg capsule or matching placebo, orally, once on Day 1, followed by a washout period of 7 days, then TAK-071 once daily for 21 days to Japanese healthy participants. Dose of TAK-071 was same as the dose used in MRD Cohort 8. TAK-071 15 mg capsule, orally, once on Day 1, followed by a washout period of 7 days, then TAK-071 once daily for 21 days to Japanese healthy participants. Dose of TAK-071 was same as the dose used in MRD Cohort 9.
Measure Participants 5 5 5
Mean (Standard Deviation) [h*ng/mL]
1485
(271.95)
4201
(822.67)
5581
(1141.6)
38. Primary Outcome
Title AUC(0-24): Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours for TAK-071 MRD Japanese Participants [Day 8]
Description
Time Frame Pre-dose on Day 8 and multiple time points (up to 24 hours) post-dose

Outcome Measure Data

Analysis Population Description
PK set included all participants who received study drug and had at least 1 measurable plasma concentration or amount of drug in the urine.
Arm/Group Title MRD: Cohort 13: TAK-071 3 mg MRD: Cohort 14: TAK-071 9 mg MRD: Cohort 15: TAK-071 15 mg
Arm/Group Description TAK-071 3 mg capsule, orally, once on Day 1, followed by a washout period of 7 days, then TAK-071 once daily for 21 days to Japanese healthy participants. Dose of TAK-071 was same as the dose used in MRD Cohort 7. TAK-071 9 mg capsule or matching placebo, orally, once on Day 1, followed by a washout period of 7 days, then TAK-071 once daily for 21 days to Japanese healthy participants. Dose of TAK-071 was same as the dose used in MRD Cohort 8. TAK-071 15 mg capsule, orally, once on Day 1, followed by a washout period of 7 days, then TAK-071 once daily for 21 days to Japanese healthy participants. Dose of TAK-071 was same as the dose used in MRD Cohort 9.
Measure Participants 5 5 5
Mean (Standard Deviation) [h*ng/mL]
1529
(344.00)
4634
(787.02)
6110
(1217.2)
39. Primary Outcome
Title AUC(0-24): Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours for TAK-071 MRD Japanese Participants [Day 28]
Description
Time Frame Pre-dose on Day 28 and multiple time points (up to 24 hours) post-dose

Outcome Measure Data

Analysis Population Description
PK set included all participants who received study drug and had at least 1 measurable plasma concentration or amount of drug in the urine.
Arm/Group Title MRD: Cohort 13: TAK-071 3 mg MRD: Cohort 14: TAK-071 9 mg MRD: Cohort 15: TAK-071 15 mg
Arm/Group Description TAK-071 3 mg capsule, orally, once on Day 1, followed by a washout period of 7 days, then TAK-071 once daily for 21 days to Japanese healthy participants. Dose of TAK-071 was same as the dose used in MRD Cohort 7. TAK-071 9 mg capsule or matching placebo, orally, once on Day 1, followed by a washout period of 7 days, then TAK-071 once daily for 21 days to Japanese healthy participants. Dose of TAK-071 was same as the dose used in MRD Cohort 8. TAK-071 15 mg capsule, orally, once on Day 1, followed by a washout period of 7 days, then TAK-071 once daily for 21 days to Japanese healthy participants. Dose of TAK-071 was same as the dose used in MRD Cohort 9.
Measure Participants 5 5 5
Mean (Standard Deviation) [h*ng/mL]
4439
(1135.6)
13450
(3024.3)
17120
(8088.8)
40. Primary Outcome
Title AUC(0-24): Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours for TAK-071 MRD Non-Japanese Participants [Day 1]
Description
Time Frame Pre-dose on Day 1 and multiple time points (up to 24 hours) post-dose

Outcome Measure Data

Analysis Population Description
PK set included all participants who received study drug and had at least 1 measurable plasma concentration or amount of drug in the urine.
Arm/Group Title MRD: Cohort 10: TAK-071 3 mg+Donepezil 5 mg MRD: Cohort 11: TAK-071 9 mg + Donepezil 5 mg MRD: Cohort 12: TAK-071 15 mg+Donepezil 5 mg
Arm/Group Description TAK-071 3 mg capsules, orally, once daily along with donepezil 5 mg, tablets, orally, once daily from Day 1 up to Day 21 to non-Japanese healthy participants who were pre-treated with donepezil 5 mg, tablet, once daily for 3 weeks prior to administration of TAK-071. Dose of TAK-071 was same as the dose used in MRD Cohort 7. TAK-071 9 mg capsules, orally, once daily along with donepezil 5 mg, tablets, orally, once daily from Day 1 up to Day 21 to non-Japanese healthy participants who were pre-treated with donepezil 5 mg, tablet, once daily for 3 weeks prior to administration of TAK-071. Dose of TAK-071 was same as the dose used in MRD Cohort 8. TAK-071 15 mg capsule, orally, once daily along with donepezil 5 mg, tablets, orally, once daily from Day 1 up to Day 21 to non-Japanese healthy participants who were pre-treated with donepezil 5 mg, tablet, once daily for 3 weeks prior to administration of TAK-071. Dose of TAK-071 was same as the dose used in MRD Cohort 9.
Measure Participants 6 6 6
Mean (Standard Deviation) [h*ng/mL]
1442
(251.62)
3636
(286.83)
5832
(921.06)
41. Primary Outcome
Title AUC(0-24): Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours for TAK-071 MRD Non-Japanese Participants [Day 21]
Description
Time Frame Pre-dose on Day 21 and multiple time points (up to 24 hours) post-dose

Outcome Measure Data

Analysis Population Description
PK set included all participants who received study drug and had at least 1 measurable plasma concentration or amount of drug in the urine.
Arm/Group Title MRD: Cohort 10: TAK-071 3 mg+Donepezil 5 mg MRD: Cohort 11: TAK-071 9 mg + Donepezil 5 mg MRD: Cohort 12: TAK-071 15 mg+Donepezil 5 mg
Arm/Group Description TAK-071 3 mg capsules, orally, once daily along with donepezil 5 mg, tablets, orally, once daily from Day 1 up to Day 21 to non-Japanese healthy participants who were pre-treated with donepezil 5 mg, tablet, once daily for 3 weeks prior to administration of TAK-071. Dose of TAK-071 was same as the dose used in MRD Cohort 7. TAK-071 9 mg capsules, orally, once daily along with donepezil 5 mg, tablets, orally, once daily from Day 1 up to Day 21 to non-Japanese healthy participants who were pre-treated with donepezil 5 mg, tablet, once daily for 3 weeks prior to administration of TAK-071. Dose of TAK-071 was same as the dose used in MRD Cohort 8. TAK-071 15 mg capsule, orally, once daily along with donepezil 5 mg, tablets, orally, once daily from Day 1 up to Day 21 to non-Japanese healthy participants who were pre-treated with donepezil 5 mg, tablet, once daily for 3 weeks prior to administration of TAK-071. Dose of TAK-071 was same as the dose used in MRD Cohort 9.
Measure Participants 6 6 6
Mean (Standard Deviation) [h*ng/mL]
4467
(1461.6)
13570
(1647.0)
19210
(4669.4)
42. Primary Outcome
Title AUC∞: Area Under the Plasma Concentration-Time Curve From Time 0 to Infinity for TAK-071 Relative Bioavailability and Food Effect
Description
Time Frame Pre-dose on Day 21 and multiple time points (up to 168 hours) post-dose

Outcome Measure Data

Analysis Population Description
PK set included all participants who received study drug and had at least 1 measurable plasma concentration or amount of drug in the urine.
Arm/Group Title Bioavailability (BA)/Food Effect: Cohort 17 Regimen A BA/Food Effect: Cohort 17 Regimen B BA/Food Effect: Cohort 17 Regimen C
Arm/Group Description TAK-071 10 mg capsule, orally once on Day 1 in the fasted state in Period 1 or Period 2 or Period 3 TAK-071 10 mg tablet, orally, once on Day 1 in the fasted state in Period 1 or Period 2 or Period 3 TAK-071 10 mg tablet, orally, once on Day 1 in the fed state in Period 1 or Period 2 or Period 3
Measure Participants 12 12 12
Mean (Standard Deviation) [h*ng/mL]
16010
(4812.0)
15190
(4576.6)
16610
(5003.1)
43. Primary Outcome
Title AUC(0-24): Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours for TAK-071 SRD Non-Japanese Participants TAK-071+Donepezil
Description
Time Frame Pre-dose on Day 1 and at multiple time points (up to 168 hours) post-dose

Outcome Measure Data

Analysis Population Description
PK set included all participants who received study drug and had at least 1 measurable plasma concentration or amount of drug in the urine.
Arm/Group Title SRD: Cohort 20: TAK-071 40 mg+Donepezil SRD: Cohort 21: TAK-071 60 mg+Donepezil SRD: Cohort 22: TAK-071 80 mg+Donepezil
Arm/Group Description TAK-071 40 mg capsule, orally, once on Day 1 followed by donepezil 10 mg, tablets, orally, once on Day 2 to non-Japanese healthy participants. Dose of TAK-071 was based on 24-hour safety, tolerability, and preliminary plasma PK data from Cohort 19. TAK-071 60 mg capsule, orally, once on Day 1 followed by donepezil 10 mg, tablets, orally, once on Day 2 to non-Japanese healthy participants. Dose of TAK-071 was based on 24-hour safety and tolerability data from Cohort 20. TAK-071 80 mg capsule, orally, once on Day 1, followed by donepezil 10 mg, tablets, orally, once on Day 2 to non-Japanese healthy participants. Dose of TAK-071 was based on 24-hour safety and tolerability data from Cohort 21.
Measure Participants 3 6 5
Mean (Standard Deviation) [h*ng/mL]
18370
(2361.9)
12810
(2177.9)
9440
(1353.7)
44. Primary Outcome
Title AUC∞: Area Under the Concentration-Time Curve From Time 0 to Infinity, Calculated Using the Observed Value of the Last Quantifiable Concentration for TAK-071 SRD Non-Japanese Participants
Description
Time Frame Pre-dose on Day 1 and at multiple time points [up to 168 hours] post-dose

Outcome Measure Data

Analysis Population Description
PK set included all participants who received study drug and had at least 1 measurable plasma concentration or amount of drug in the urine.
Arm/Group Title SRD: Cohort 1: TAK-071 1 mg SRD: Cohort 2: TAK-071 3 mg SRD: Cohort 3: TAK-071 9 mg SRD: Cohort 4: TAK-071 20 mg SRD: Cohort 5: TAK-071 40 mg SRD: Cohort 6: TAK-071 80 mg SRD: Cohort 18: TAK-071 120 mg SRD: Cohort 19: TAK-071 160 mg
Arm/Group Description TAK-071 1 mg, capsule, orally, once on Day 1 to non-Japanese healthy participants. TAK-071 3 mg capsule, orally, once on Day 1 to non-Japanese healthy participants. Dose of TAK-071 was based on the 24-hour post-dose safety, tolerability and pharmacokinetic (PK) data from cohort 1. TAK-071 9 mg capsule, orally, once on Day 1 to non-Japanese healthy participants. Dose of TAK-071 was based on 24-hour safety, tolerability, and preliminary plasma PK and 12-hour CSF PK data. TAK-071 20 mg capsule, orally, once on Day 1 to non-Japanese healthy participants. Dose of TAK-071 was based on the 24-hour post-dose safety and tolerability data from previous cohort. TAK-071 40 mg capsule, orally, once on Day 1 to non-Japanese healthy participants. Dose of TAK-071 will be based on 24-hour safety, tolerability, and preliminary plasma PK data from Cohort 4. TAK-071 80 mg capsules, orally, once on Day 1 to non-Japanese healthy participants. Dose of TAK-071 was based on 24-hour safety, tolerability, and preliminary plasma PK data from Cohort 5 TAK-071 120 mg capsule, orally, once on Day 1 to non-Japanese healthy participants. Dose of TAK-071 was based on 24-hour safety, tolerability, and preliminary plasma PK data from Cohort 6. TAK-071 160 mg capsule, orally, once on Day 1 to non-Japanese healthy participants. Dose of TAK-071 was based on 24-hour safety, tolerability, and preliminary plasma PK data from Cohort 18.
Measure Participants 6 6 6 6 6 6 6 6
Mean (Standard Deviation) [h*ng/mL]
1651
(644.79)
5070
(3802.0)
15640
(5944.7)
30980
(5932.8)
49550
(33766)
106000
(19610)
132700
(46773)
162100
(69191)
45. Primary Outcome
Title AUC∞: Area Under the Concentration-Time Curve From Time 0 to Infinity, Calculated Using the Observed Value of the Last Quantifiable Concentration for TAK-071 SRD Non-Japanese Participants TAK-071 + Donepezil
Description
Time Frame Pre-dose on Day 1 and at multiple time points [up to 168 hours] post-dose

Outcome Measure Data

Analysis Population Description
PK set included all participants who received study drug and had at least 1 measurable plasma concentration or amount of drug in the urine.
Arm/Group Title SRD: Cohort 20: TAK-071 40 mg+Donepezil SRD: Cohort 21: TAK-071 60 mg+Donepezil SRD: Cohort 22: TAK-071 80 mg+Donepezil
Arm/Group Description TAK-071 40 mg capsule, orally, once on Day 1 followed by donepezil 10 mg, tablets, orally, once on Day 2 to non-Japanese healthy participants. Dose of TAK-071 was based on 24-hour safety, tolerability, and preliminary plasma PK data from Cohort 19. TAK-071 60 mg capsule, orally, once on Day 1 followed by donepezil 10 mg, tablets, orally, once on Day 2 to non-Japanese healthy participants. Dose of TAK-071 was based on 24-hour safety and tolerability data from Cohort 20. TAK-071 80 mg capsule, orally, once on Day 1, followed by donepezil 10 mg, tablets, orally, once on Day 2 to non-Japanese healthy participants. Dose of TAK-071 was based on 24-hour safety and tolerability data from Cohort 21.
Measure Participants 3 6 5
Mean (Standard Deviation) [h*ng/mL]
97640
(22123)
48750
(12598)
46370
(6094.8)
46. Secondary Outcome
Title AUClast: Area Under the Concentration-time Curve From Time 0 to Time of the Last Quantifiable Concentration for TAK-071 MRD Non-Japanese Participants
Description
Time Frame Pre-dose on Day 1 and at multiple time points (up to 168 hours) post-dose

Outcome Measure Data

Analysis Population Description
PK set included all participants who received study drug and had at least 1 measurable plasma concentration or amount of drug in the urine.
Arm/Group Title SRD: Cohort 1: TAK-071 1 mg SRD: Cohort 2: TAK-071 3 mg SRD: Cohort 3: TAK-071 9 mg SRD: Cohort 4: TAK-071 20 mg SRD: Cohort 5: TAK-071 40 mg SRD: Cohort 6: TAK-071 80 mg SRD: Cohort 18: TAK-071 120 mg SRD: Cohort 19: TAK-071 160 mg
Arm/Group Description TAK-071 1 mg, capsule, orally, once on Day 1 to non-Japanese healthy participants. TAK-071 3 mg capsule, orally, once on Day 1 to non-Japanese healthy participants. Dose of TAK-071 was based on the 24-hour post-dose safety, tolerability and pharmacokinetic (PK) data from cohort 1. TAK-071 9 mg capsule, orally, once on Day 1 to non-Japanese healthy participants. Dose of TAK-071 was based on 24-hour safety, tolerability, and preliminary plasma PK and 12-hour CSF PK data. TAK-071 20 mg capsule, orally, once on Day 1 to non-Japanese healthy participants. Dose of TAK-071 was based on the 24-hour post-dose safety and tolerability data from previous cohort. TAK-071 40 mg capsule, orally, once on Day 1 to non-Japanese healthy participants. Dose of TAK-071 will be based on 24-hour safety, tolerability, and preliminary plasma PK data from Cohort 4. TAK-071 80 mg capsules, orally, once on Day 1 to non-Japanese healthy participants. Dose of TAK-071 was based on 24-hour safety, tolerability, and preliminary plasma PK data from Cohort 5 TAK-071 120 mg capsule, orally, once on Day 1 to non-Japanese healthy participants. Dose of TAK-071 was based on 24-hour safety, tolerability, and preliminary plasma PK data from Cohort 6. TAK-071 160 mg capsule, orally, once on Day 1 to non-Japanese healthy participants. Dose of TAK-071 was based on 24-hour safety, tolerability, and preliminary plasma PK data from Cohort 18.
Measure Participants 6 6 6 6 6 6 6 6
Mean (Standard Deviation) [h*ng/mL]
1220
(397.35)
3945
(1784.9)
12450
(2466.5)
26010
(3656.6)
40240
(23644)
90350
(13944)
111700
(31926)
133000
(45126)
47. Secondary Outcome
Title AUClast: Area Under the Concentration-time Curve From Time 0 to Time of the Last Quantifiable Concentration for TAK-071 MRD Non-Japanese Participants
Description
Time Frame Pre-dose on Day 1 and multiple timepoints (up to 24 hrs) post-dose for Cohorts 7 and 8 and Pre-dose on Day 1 and multiple timepoints (up to 96 hrs) post-dose for Cohort 9

Outcome Measure Data

Analysis Population Description
PK set included all participants who received study drug and had at least 1 measurable plasma concentration or amount of drug in the urine.
Arm/Group Title MRD: Cohort 7: TAK-071 3 mg MRD: Cohort 8: TAK-071 9 mg MRD: Cohort 9: TAK-071 15 mg
Arm/Group Description TAK-071 3 mg capsules, orally, once daily from Day 1 up to Day 21 to non-Japanese healthy participants. Dose of TAK-071 was based on 24-hour safety and tolerability from Cohort 4 and the 24-hour preliminary plasma PK and 12-hour CSF PK data from Cohort 3. TAK-071 9 mg capsules, orally, once daily from Day 1 up to Day 21 to non-Japanese healthy participants. Dose of TAK-071 was based on safety, tolerability and available PK data arising from the ongoing SRD part and previous MRD cohort. TAK-071 15 mg capsule, orally, once on Day 1, followed by a washout period of 7 days, then TAK-071 once daily for 21 days to non-Japanese healthy participants. Dose of TAK-071 will be based on safety, tolerability and available PK data arising from the ongoing SRD part and previous MRD cohort.
Measure Participants 6 6 6
Mean (Standard Deviation) [h*ng/mL]
1347
(302.98)
3550
(765.01)
16880
(4514.9)
48. Secondary Outcome
Title AUClast: Area Under the Concentration-time Curve From Time 0 to Time of the Last Quantifiable Concentration for TAK-071 MRD Japanese Participants
Description
Time Frame Pre-dose on Day 1 and multiple time points (up to 96 hours) post-dose and Pre-dose on Day 8 and multiple time points (up to 24 hours) post-dose

Outcome Measure Data

Analysis Population Description
PK set included all participants who received study drug and had at least 1 measurable plasma concentration or amount of drug in the urine.
Arm/Group Title MRD: Cohort 13: TAK-071 3 mg MRD: Cohort 14: TAK-071 9 mg MRD: Cohort 15: TAK-071 15 mg
Arm/Group Description TAK-071 3 mg capsule, orally, once on Day 1, followed by a washout period of 7 days, then TAK-071 once daily for 21 days to Japanese healthy participants. Dose of TAK-071 was same as the dose used in MRD Cohort 7. TAK-071 9 mg capsule or matching placebo, orally, once on Day 1, followed by a washout period of 7 days, then TAK-071 once daily for 21 days to Japanese healthy participants. Dose of TAK-071 was same as the dose used in MRD Cohort 8. TAK-071 15 mg capsule, orally, once on Day 1, followed by a washout period of 7 days, then TAK-071 once daily for 21 days to Japanese healthy participants. Dose of TAK-071 was same as the dose used in MRD Cohort 9.
Measure Participants 5 5 5
Day 1
3773
(968.76)
11930
(2764.4)
15790
(3273.2)
Day 8
1529
(344.00)
4634
(787.02)
6110
(1217.2)
49. Secondary Outcome
Title AUClast: Area Under the Concentration-time Curve From Time 0 to Time of the Last Quantifiable Concentration for TAK-071 MRD Non-Japanese
Description
Time Frame Pre-dose on Day 1 and at multiple time points (up to 24 hours) post-dose

Outcome Measure Data

Analysis Population Description
PK set included all participants who received study drug and had at least 1 measurable plasma concentration or amount of drug in the urine.
Arm/Group Title MRD: Cohort 10: TAK-071 3 mg+Donepezil 5 mg MRD: Cohort 11: TAK-071 9 mg + Donepezil 5 mg MRD: Cohort 12: TAK-071 15 mg+Donepezil 5 mg
Arm/Group Description TAK-071 3 mg capsules, orally, once daily along with donepezil 5 mg, tablets, orally, once daily from Day 1 up to Day 21 to non-Japanese healthy participants who were pre-treated with donepezil 5 mg, tablet, once daily for 3 weeks prior to administration of TAK-071. Dose of TAK-071 was same as the dose used in MRD Cohort 7. TAK-071 9 mg capsules, orally, once daily along with donepezil 5 mg, tablets, orally, once daily from Day 1 up to Day 21 to non-Japanese healthy participants who were pre-treated with donepezil 5 mg, tablet, once daily for 3 weeks prior to administration of TAK-071. Dose of TAK-071 was same as the dose used in MRD Cohort 8. TAK-071 15 mg capsule, orally, once daily along with donepezil 5 mg, tablets, orally, once daily from Day 1 up to Day 21 to non-Japanese healthy participants who were pre-treated with donepezil 5 mg, tablet, once daily for 3 weeks prior to administration of TAK-071. Dose of TAK-071 was same as the dose used in MRD Cohort 9.
Measure Participants 6 6 6
Mean (Standard Deviation) [h*ng/mL]
1442
(251.62)
3636
(286.83)
5832
(921.06)
50. Secondary Outcome
Title AUClast: Area Under the Concentration-time Curve From Time 0 to Time of the Last Quantifiable Concentration for TAK-071 Relative Bioavailability and Food Effect
Description
Time Frame Pre-dose on Day 1 and multiple time points (up to 168 hours) post-dose

Outcome Measure Data

Analysis Population Description
PK set included all participants who received study drug and had at least 1 measurable plasma concentration or amount of drug in the urine.
Arm/Group Title Bioavailability (BA)/Food Effect: Cohort 17 Regimen A BA/Food Effect: Cohort 17 Regimen B BA/Food Effect: Cohort 17 Regimen C
Arm/Group Description TAK-071 10 mg capsule, orally once on Day 1 in the fasted state in Period 1 or Period 2 or Period 3 TAK-071 10 mg tablet, orally, once on Day 1 in the fasted state in Period 1 or Period 2 or Period 3 TAK-071 10 mg tablet, orally, once on Day 1 in the fed state in Period 1 or Period 2 or Period 3
Measure Participants 12 12 12
Mean (Standard Deviation) [h*ng/mL]
14210
(3392.5)
13260
(2983.9)
14610
(3324.3)
51. Secondary Outcome
Title AUClast: Area Under the Concentration-time Curve From Time 0 to Time of the Last Quantifiable Concentration for TAK-071 SRD Non-Japanese Participants TAK-071+Donepezil
Description
Time Frame Pre-dose on Day 1 and multiple time points (up to 168 hours) post-dose

Outcome Measure Data

Analysis Population Description
PK set included all participants who received study drug and had at least 1 measurable plasma concentration or amount of drug in the urine.
Arm/Group Title SRD: Cohort 20: TAK-071 40 mg+Donepezil SRD: Cohort 21: TAK-071 60 mg+Donepezil SRD: Cohort 22: TAK-071 80 mg+Donepezil
Arm/Group Description TAK-071 40 mg capsule, orally, once on Day 1 followed by donepezil 10 mg, tablets, orally, once on Day 2 to non-Japanese healthy participants. Dose of TAK-071 was based on 24-hour safety, tolerability, and preliminary plasma PK data from Cohort 19. TAK-071 60 mg capsule, orally, once on Day 1 followed by donepezil 10 mg, tablets, orally, once on Day 2 to non-Japanese healthy participants. Dose of TAK-071 was based on 24-hour safety and tolerability data from Cohort 20. TAK-071 80 mg capsule, orally, once on Day 1, followed by donepezil 10 mg, tablets, orally, once on Day 2 to non-Japanese healthy participants. Dose of TAK-071 was based on 24-hour safety and tolerability data from Cohort 21.
Measure Participants 3 6 5
Mean (Standard Deviation) [h*ng/mL]
85650
(13013)
45970
(10798)
41070
(4387.9)
52. Secondary Outcome
Title Terminal Disposition Phase Half-life (t1/2z) for TAK-071 SRD Non-Japanese Participants
Description
Time Frame Pre-dose on Day 1 and at multiple time points (up to 168 hours) post-dose

Outcome Measure Data

Analysis Population Description
PK set included all participants who received study drug and had at least 1 measurable plasma concentration or amount of drug in the urine.
Arm/Group Title SRD: Cohort 1: TAK-071 1 mg SRD: Cohort 2: TAK-071 3 mg SRD: Cohort 3: TAK-071 9 mg SRD: Cohort 4: TAK-071 20 mg SRD: Cohort 5: TAK-071 40 mg SRD: Cohort 6: TAK-071 80 mg SRD: Cohort 18: TAK-071 120 mg SRD: Cohort 19: TAK-071 160 mg
Arm/Group Description TAK-071 1 mg, capsule, orally, once on Day 1 to non-Japanese healthy participants. TAK-071 3 mg capsule, orally, once on Day 1 to non-Japanese healthy participants. Dose of TAK-071 was based on the 24-hour post-dose safety, tolerability and pharmacokinetic (PK) data from cohort 1. TAK-071 9 mg capsule, orally, once on Day 1 to non-Japanese healthy participants. Dose of TAK-071 was based on 24-hour safety, tolerability, and preliminary plasma PK and 12-hour CSF PK data. TAK-071 20 mg capsule, orally, once on Day 1 to non-Japanese healthy participants. Dose of TAK-071 was based on the 24-hour post-dose safety and tolerability data from previous cohort. TAK-071 40 mg capsule, orally, once on Day 1 to non-Japanese healthy participants. Dose of TAK-071 will be based on 24-hour safety, tolerability, and preliminary plasma PK data from Cohort 4. TAK-071 80 mg capsules, orally, once on Day 1 to non-Japanese healthy participants. Dose of TAK-071 was based on 24-hour safety, tolerability, and preliminary plasma PK data from Cohort 5 TAK-071 120 mg capsule, orally, once on Day 1 to non-Japanese healthy participants. Dose of TAK-071 was based on 24-hour safety, tolerability, and preliminary plasma PK data from Cohort 6. TAK-071 160 mg capsule, orally, once on Day 1 to non-Japanese healthy participants. Dose of TAK-071 was based on 24-hour safety, tolerability, and preliminary plasma PK data from Cohort 18.
Measure Participants 6 6 6 6 6 6 6 6
Median (Full Range) [hours]
50.894
35.567
54.998
57.504
53.219
55.246
51.933
58.165
53. Secondary Outcome
Title Terminal Disposition Phase Half-life (t1/2z) for TAK-071 Relative Bioavailability and Food Effect
Description
Time Frame Pre-dose on Day 21 and multiple time points (up to 168 hours) post-dose

Outcome Measure Data

Analysis Population Description
PK set included all participants who received study drug and had at least 1 measurable plasma concentration or amount of drug in the urine.
Arm/Group Title Bioavailability (BA)/Food Effect: Cohort 17 Regimen A BA/Food Effect: Cohort 17 Regimen B BA/Food Effect: Cohort 17 Regimen C
Arm/Group Description TAK-071 10 mg capsule, orally once on Day 1 in the fasted state in Period 1 or Period 2 or Period 3 TAK-071 10 mg tablet, orally, once on Day 1 in the fasted state in Period 1 or Period 2 or Period 3 TAK-071 10 mg tablet, orally, once on Day 1 in the fed state in Period 1 or Period 2 or Period 3
Measure Participants 12 12 12
Median (Full Range) [hours]
48.804
50.590
49.796
54. Secondary Outcome
Title Terminal Disposition Phase Half-life (t1/2z) for TAK-071 SRD Non-Japanese Participants TAK-071+Donepezil
Description
Time Frame Pre-dose on Day 1 and multiple time points (up to 168 hours) post-dose

Outcome Measure Data

Analysis Population Description
PK set included all participants who received study drug and had at least 1 measurable plasma concentration or amount of drug in the urine.
Arm/Group Title SRD: Cohort 20: TAK-071 40 mg+Donepezil SRD: Cohort 21: TAK-071 60 mg+Donepezil SRD: Cohort 22: TAK-071 80 mg+Donepezil
Arm/Group Description TAK-071 40 mg capsule, orally, once on Day 1 followed by donepezil 10 mg, tablets, orally, once on Day 2 to non-Japanese healthy participants. Dose of TAK-071 was based on 24-hour safety, tolerability, and preliminary plasma PK data from Cohort 19. TAK-071 60 mg capsule, orally, once on Day 1 followed by donepezil 10 mg, tablets, orally, once on Day 2 to non-Japanese healthy participants. Dose of TAK-071 was based on 24-hour safety and tolerability data from Cohort 20. TAK-071 80 mg capsule, orally, once on Day 1, followed by donepezil 10 mg, tablets, orally, once on Day 2 to non-Japanese healthy participants. Dose of TAK-071 was based on 24-hour safety and tolerability data from Cohort 21.
Measure Participants 3 6 5
Median (Full Range) [hours]
42.923
33.505
50.077
55. Secondary Outcome
Title CL/F: Apparent Clearance After Extravascular Administration for TAK-071 SRD Non-Japanese Participants
Description
Time Frame Pre-dose on Day 1 and at multiple time points (up to 168 hours) post-dose

Outcome Measure Data

Analysis Population Description
PK set included all participants who received study drug and had at least 1 measurable plasma concentration or amount of drug in the urine.
Arm/Group Title SRD: Cohort 1: TAK-071 1 mg SRD: Cohort 2: TAK-071 3 mg SRD: Cohort 3: TAK-071 9 mg SRD: Cohort 4: TAK-071 20 mg SRD: Cohort 5: TAK-071 40 mg SRD: Cohort 6: TAK-071 80 mg SRD: Cohort 18: TAK-071 120 mg SRD: Cohort 19: TAK-071 160 mg
Arm/Group Description TAK-071 1 mg, capsule, orally, once on Day 1 to non-Japanese healthy participants. TAK-071 3 mg capsule, orally, once on Day 1 to non-Japanese healthy participants. Dose of TAK-071 was based on the 24-hour post-dose safety, tolerability and pharmacokinetic (PK) data from cohort 1. TAK-071 9 mg capsule, orally, once on Day 1 to non-Japanese healthy participants. Dose of TAK-071 was based on 24-hour safety, tolerability, and preliminary plasma PK and 12-hour CSF PK data. TAK-071 20 mg capsule, orally, once on Day 1 to non-Japanese healthy participants. Dose of TAK-071 was based on the 24-hour post-dose safety and tolerability data from previous cohort. TAK-071 40 mg capsule, orally, once on Day 1 to non-Japanese healthy participants. Dose of TAK-071 will be based on 24-hour safety, tolerability, and preliminary plasma PK data from Cohort 4. TAK-071 80 mg capsules, orally, once on Day 1 to non-Japanese healthy participants. Dose of TAK-071 was based on 24-hour safety, tolerability, and preliminary plasma PK data from Cohort 5 TAK-071 120 mg capsule, orally, once on Day 1 to non-Japanese healthy participants. Dose of TAK-071 was based on 24-hour safety, tolerability, and preliminary plasma PK data from Cohort 6. TAK-071 160 mg capsule, orally, once on Day 1 to non-Japanese healthy participants. Dose of TAK-071 was based on 24-hour safety, tolerability, and preliminary plasma PK data from Cohort 18.
Measure Participants 6 6 6 6 6 6 6 6
Mean (Standard Deviation) [L/h]
0.7222
(0.36130)
0.7998
(0.36546)
0.6494
(0.24348)
0.6644
(0.12027)
3.844
(7.3558)
0.7762
(0.13868)
1.008
(0.36826)
1.141
(0.45838)
56. Secondary Outcome
Title CL/F: Apparent Clearance After Extravascular Administration for TAK-071 Relative Bioavailability and Food Effect
Description
Time Frame Pre-dose on Day 21 and multiple time points (up to 168 hours) post-dose

Outcome Measure Data

Analysis Population Description
PK set included all participants who received study drug and had at least 1 measurable plasma concentration or amount of drug in the urine.
Arm/Group Title Bioavailability (BA)/Food Effect: Cohort 17 Regimen A BA/Food Effect: Cohort 17 Regimen B BA/Food Effect: Cohort 17 Regimen C
Arm/Group Description TAK-071 10 mg capsule, orally once on Day 1 in the fasted state in Period 1 or Period 2 or Period 3 TAK-071 10 mg tablet, orally, once on Day 1 in the fasted state in Period 1 or Period 2 or Period 3 TAK-071 10 mg tablet, orally, once on Day 1 in the fed state in Period 1 or Period 2 or Period 3
Measure Participants 12 12 12
Mean (Standard Deviation) [L/h]
0.6925
(0.27468)
0.7232
(0.26191)
0.6663
(0.25695)
57. Secondary Outcome
Title CL/F: Apparent Clearance After Extravascular Administration for TAK-071 SRD Non-Japanese Participants TAK-071+Donepezil
Description
Time Frame Pre-dose on Day 1 and at multiple time points (up to 168 hours) post-dose

Outcome Measure Data

Analysis Population Description
PK set included all participants who received study drug and had at least 1 measurable plasma concentration or amount of drug in the urine.
Arm/Group Title SRD: Cohort 20: TAK-071 40 mg+Donepezil SRD: Cohort 21: TAK-071 60 mg+Donepezil SRD: Cohort 22: TAK-071 80 mg+Donepezil
Arm/Group Description TAK-071 40 mg capsule, orally, once on Day 1 followed by donepezil 10 mg, tablets, orally, once on Day 2 to non-Japanese healthy participants. Dose of TAK-071 was based on 24-hour safety, tolerability, and preliminary plasma PK data from Cohort 19. TAK-071 60 mg capsule, orally, once on Day 1 followed by donepezil 10 mg, tablets, orally, once on Day 2 to non-Japanese healthy participants. Dose of TAK-071 was based on 24-hour safety and tolerability data from Cohort 20. TAK-071 80 mg capsule, orally, once on Day 1, followed by donepezil 10 mg, tablets, orally, once on Day 2 to non-Japanese healthy participants. Dose of TAK-071 was based on 24-hour safety and tolerability data from Cohort 21.
Measure Participants 3 6 5
Mean (Standard Deviation) [L/h]
0.8453
(0.17228)
1.304
(0.34484)
0.8742
(0.11009)
58. Secondary Outcome
Title Vz/F: Apparent Volume of Distribution During the Terminal Disposition Phase After Extravascular Administration for TAK-071 SRD Non-Japanese Participants
Description
Time Frame Pre-dose on Day 1 and at multiple time points (up to 168 hours) post-dose

Outcome Measure Data

Analysis Population Description
PK set included all participants who received study drug and had at least 1 measurable plasma concentration or amount of drug in the urine.
Arm/Group Title SRD: Cohort 1: TAK-071 1 mg SRD: Cohort 2: TAK-071 3 mg SRD: Cohort 3: TAK-071 9 mg SRD: Cohort 4: TAK-071 20 mg SRD: Cohort 5: TAK-071 40 mg SRD: Cohort 6: TAK-071 80 mg SRD: Cohort 18: TAK-071 120 mg SRD: Cohort 19: TAK-071 160 mg
Arm/Group Description TAK-071 1 mg, capsule, orally, once on Day 1 to non-Japanese healthy participants. TAK-071 3 mg capsule, orally, once on Day 1 to non-Japanese healthy participants. Dose of TAK-071 was based on the 24-hour post-dose safety, tolerability and pharmacokinetic (PK) data from cohort 1. TAK-071 9 mg capsule, orally, once on Day 1 to non-Japanese healthy participants. Dose of TAK-071 was based on 24-hour safety, tolerability, and preliminary plasma PK and 12-hour CSF PK data. TAK-071 20 mg capsule, orally, once on Day 1 to non-Japanese healthy participants. Dose of TAK-071 was based on the 24-hour post-dose safety and tolerability data from previous cohort. TAK-071 40 mg capsule, orally, once on Day 1 to non-Japanese healthy participants. Dose of TAK-071 will be based on 24-hour safety, tolerability, and preliminary plasma PK data from Cohort 4. TAK-071 80 mg capsules, orally, once on Day 1 to non-Japanese healthy participants. Dose of TAK-071 was based on 24-hour safety, tolerability, and preliminary plasma PK data from Cohort 5 TAK-071 120 mg capsule, orally, once on Day 1 to non-Japanese healthy participants. Dose of TAK-071 was based on 24-hour safety, tolerability, and preliminary plasma PK data from Cohort 6. TAK-071 160 mg capsule, orally, once on Day 1 to non-Japanese healthy participants. Dose of TAK-071 was based on 24-hour safety, tolerability, and preliminary plasma PK data from Cohort 18.
Measure Participants 6 6 6 6 6 6 6 6
Mean (Standard Deviation) [L]
43.63
(10.532)
44.96
(5.7176)
48.10
(9.0985)
54.62
(9.8917)
321.0
(656.95)
59.54
(11.499)
70.25
(9.1042)
84.47
(16.851)
59. Secondary Outcome
Title Vz/F: Apparent Volume of Distribution During the Terminal Disposition Phase After Extravascular Administration for TAK-071 Relative Bioavailability and Food Effect
Description
Time Frame Pre-dose on Day 21 and multiple time points (up to 168 hours) post-dose

Outcome Measure Data

Analysis Population Description
PK set included all participants who received study drug and had at least 1 measurable plasma concentration or amount of drug in the urine.
Arm/Group Title Bioavailability (BA)/Food Effect: Cohort 17 Regimen A BA/Food Effect: Cohort 17 Regimen B BA/Food Effect: Cohort 17 Regimen C
Arm/Group Description TAK-071 10 mg capsule, orally once on Day 1 in the fasted state in Period 1 or Period 2 or Period 3 TAK-071 10 mg tablet, orally, once on Day 1 in the fasted state in Period 1 or Period 2 or Period 3 TAK-071 10 mg tablet, orally, once on Day 1 in the fed state in Period 1 or Period 2 or Period 3
Measure Participants 12 12 12
Mean (Standard Deviation) [L]
44.43
(7.1688)
46.74
(7.3595)
43.82
(6.3235)
60. Secondary Outcome
Title Vz/F: Apparent Volume of Distribution During the Terminal Disposition Phase After Extravascular Administration for TAK-071 SRD Non-Japanese Participants TAK-071 + Donepezil
Description
Time Frame Pre-dose on Day 1 and at multiple time points (up to 168 hours) post-dose

Outcome Measure Data

Analysis Population Description
PK set included all participants who received study drug and had at least 1 measurable plasma concentration or amount of drug in the urine.
Arm/Group Title SRD: Cohort 20: TAK-071 40 mg+Donepezil SRD: Cohort 21: TAK-071 60 mg+Donepezil SRD: Cohort 22: TAK-071 80 mg+Donepezil
Arm/Group Description TAK-071 40 mg capsule, orally, once on Day 1 followed by donepezil 10 mg, tablets, orally, once on Day 2 to non-Japanese healthy participants. Dose of TAK-071 was based on 24-hour safety, tolerability, and preliminary plasma PK data from Cohort 19. TAK-071 60 mg capsule, orally, once on Day 1 followed by donepezil 10 mg, tablets, orally, once on Day 2 to non-Japanese healthy participants. Dose of TAK-071 was based on 24-hour safety and tolerability data from Cohort 20. TAK-071 80 mg capsule, orally, once on Day 1, followed by donepezil 10 mg, tablets, orally, once on Day 2 to non-Japanese healthy participants. Dose of TAK-071 was based on 24-hour safety and tolerability data from Cohort 21.
Measure Participants 3 6 5
Mean (Standard Deviation) [L]
59.03
(5.5208)
62.40
(17.164)
63.52
(11.895)
61. Secondary Outcome
Title Accumulation Ratio Based on AUCτ (Rac[AUC]) for TAK-071 MRD Non-Japanese Participants
Description
Time Frame Pre-dose on Day 21 and at multiple time points (up to 24 hours) post-dose for Cohorts 7 and 8 and Pre-dose on Day 28 and at multiple time points (up to 36 hours) post-dose for Cohort 9

Outcome Measure Data

Analysis Population Description
PK set included all participants who received study drug and had at least 1 measurable plasma concentration or amount of drug in the urine.
Arm/Group Title MRD: Cohort 7: TAK-071 3 mg MRD: Cohort 8: TAK-071 9 mg MRD: Cohort 9: TAK-071 15 mg
Arm/Group Description TAK-071 3 mg capsules, orally, once daily from Day 1 up to Day 21 to non-Japanese healthy participants. Dose of TAK-071 was based on 24-hour safety and tolerability from Cohort 4 and the 24-hour preliminary plasma PK and 12-hour CSF PK data from Cohort 3. TAK-071 9 mg capsules, orally, once daily from Day 1 up to Day 21 to non-Japanese healthy participants. Dose of TAK-071 was based on safety, tolerability and available PK data arising from the ongoing SRD part and previous MRD cohort. TAK-071 15 mg capsule, orally, once on Day 1, followed by a washout period of 7 days, then TAK-071 once daily for 21 days to non-Japanese healthy participants. Dose of TAK-071 will be based on safety, tolerability and available PK data arising from the ongoing SRD part and previous MRD cohort.
Measure Participants 6 6 5
Mean (Standard Deviation) [Ratio]
3.568
(0.71765)
3.713
(1.1916)
3.778
(1.2626)
62. Secondary Outcome
Title Accumulation Ratio Based on AUCτ (Rac[AUC]) for TAK-071 MRD Japanese Participants
Description
Time Frame Pre-dose on Day 28 and at multiple time points [up to 24 hours] post-dose

Outcome Measure Data

Analysis Population Description
PK set included all participants who received study drug and had at least 1 measurable plasma concentration or amount of drug in the urine.
Arm/Group Title MRD: Cohort 13: TAK-071 3 mg MRD: Cohort 14: TAK-071 9 mg MRD: Cohort 15: TAK-071 15 mg
Arm/Group Description TAK-071 3 mg capsule, orally, once on Day 1, followed by a washout period of 7 days, then TAK-071 once daily for 21 days to Japanese healthy participants. Dose of TAK-071 was same as the dose used in MRD Cohort 7. TAK-071 9 mg capsule or matching placebo, orally, once on Day 1, followed by a washout period of 7 days, then TAK-071 once daily for 21 days to Japanese healthy participants. Dose of TAK-071 was same as the dose used in MRD Cohort 8. TAK-071 15 mg capsule, orally, once on Day 1, followed by a washout period of 7 days, then TAK-071 once daily for 21 days to Japanese healthy participants. Dose of TAK-071 was same as the dose used in MRD Cohort 9.
Measure Participants 5 5 5
Mean (Standard Deviation) [Ratio]
2.973
(0.38747)
3.241
(0.56613)
3.096
(1.4212)
63. Secondary Outcome
Title Accumulation Ratio Based on AUCτ (Rac[AUC]) for TAK-071 MRD Non-Japanese Participants
Description
Time Frame Pre-dose on Day 21 and at multiple time points [up to 24 hours] post-dose

Outcome Measure Data

Analysis Population Description
PK set included all participants who received study drug and had at least 1 measurable plasma concentration or amount of drug in the urine.
Arm/Group Title MRD: Cohort 10: TAK-071 3 mg+Donepezil 5 mg MRD: Cohort 11: TAK-071 9 mg + Donepezil 5 mg MRD: Cohort 12: TAK-071 15 mg+Donepezil 5 mg
Arm/Group Description TAK-071 3 mg capsules, orally, once daily along with donepezil 5 mg, tablets, orally, once daily from Day 1 up to Day 21 to non-Japanese healthy participants who were pre-treated with donepezil 5 mg, tablet, once daily for 3 weeks prior to administration of TAK-071. Dose of TAK-071 was same as the dose used in MRD Cohort 7. TAK-071 9 mg capsules, orally, once daily along with donepezil 5 mg, tablets, orally, once daily from Day 1 up to Day 21 to non-Japanese healthy participants who were pre-treated with donepezil 5 mg, tablet, once daily for 3 weeks prior to administration of TAK-071. Dose of TAK-071 was same as the dose used in MRD Cohort 8. TAK-071 15 mg capsule, orally, once daily along with donepezil 5 mg, tablets, orally, once daily from Day 1 up to Day 21 to non-Japanese healthy participants who were pre-treated with donepezil 5 mg, tablet, once daily for 3 weeks prior to administration of TAK-071. Dose of TAK-071 was same as the dose used in MRD Cohort 9.
Measure Participants 6 6 6
Mean (Standard Deviation) [Ratio]
3.099
(0.75130)
3.749
(0.55862)
3.350
(0.92710)
64. Secondary Outcome
Title Accumulation Ratio Based on Plasma Cmax (Rac[Cmax]) for TAK-071 MRD Non-Japanese Participants
Description
Time Frame Pre-dose on Day 21 and at multiple time points [up to 24 hours] post-dose for Cohorts 7 and 8 and Pre-dose on Day 28 and at multiple time points (up to 36 hours) post-dose for Cohort 9

Outcome Measure Data

Analysis Population Description
PK set included all participants who received study drug and had at least 1 measurable plasma concentration or amount of drug in the urine.
Arm/Group Title MRD: Cohort 7: TAK-071 3 mg MRD: Cohort 8: TAK-071 9 mg MRD: Cohort 9: TAK-071 15 mg
Arm/Group Description TAK-071 3 mg capsules, orally, once daily from Day 1 up to Day 21 to non-Japanese healthy participants. Dose of TAK-071 was based on 24-hour safety and tolerability from Cohort 4 and the 24-hour preliminary plasma PK and 12-hour CSF PK data from Cohort 3. TAK-071 9 mg capsules, orally, once daily from Day 1 up to Day 21 to non-Japanese healthy participants. Dose of TAK-071 was based on safety, tolerability and available PK data arising from the ongoing SRD part and previous MRD cohort. TAK-071 15 mg capsule, orally, once on Day 1, followed by a washout period of 7 days, then TAK-071 once daily for 21 days to non-Japanese healthy participants. Dose of TAK-071 will be based on safety, tolerability and available PK data arising from the ongoing SRD part and previous MRD cohort.
Measure Participants 6 6 5
Mean (Standard Deviation) [Ratio]
3.297
(0.59164)
3.578
(1.2955)
3.541
(0.86317)
65. Secondary Outcome
Title Accumulation Ratio Based on Plasma Cmax (Rac[Cmax]) for TAK-071 MRD Japanese Participants
Description
Time Frame Pre-dose on Day 28 and at multiple time points [up to 24 hours] post-dose

Outcome Measure Data

Analysis Population Description
PK set included all participants who received study drug and had at least 1 measurable plasma concentration or amount of drug in the urine.
Arm/Group Title MRD: Cohort 13: TAK-071 3 mg MRD: Cohort 14: TAK-071 9 mg MRD: Cohort 15: TAK-071 15 mg
Arm/Group Description TAK-071 3 mg capsule, orally, once on Day 1, followed by a washout period of 7 days, then TAK-071 once daily for 21 days to Japanese healthy participants. Dose of TAK-071 was same as the dose used in MRD Cohort 7. TAK-071 9 mg capsule or matching placebo, orally, once on Day 1, followed by a washout period of 7 days, then TAK-071 once daily for 21 days to Japanese healthy participants. Dose of TAK-071 was same as the dose used in MRD Cohort 8. TAK-071 15 mg capsule, orally, once on Day 1, followed by a washout period of 7 days, then TAK-071 once daily for 21 days to Japanese healthy participants. Dose of TAK-071 was same as the dose used in MRD Cohort 9.
Measure Participants 5 5 5
Mean (Standard Deviation) [Ratio]
2.960
(0.26180)
3.327
(0.74832)
3.285
(1.5406)
66. Secondary Outcome
Title Accumulation Ratio Based on Plasma Cmax (Rac[Cmax]) for TAK-071 MRD Non-Japanese Participants
Description
Time Frame Pre-dose on Day 21 and at multiple time points [up to 24 hours] post-dose

Outcome Measure Data

Analysis Population Description
PK set included all participants who received study drug and had at least 1 measurable plasma concentration or amount of drug in the urine.
Arm/Group Title MRD: Cohort 10: TAK-071 3 mg+Donepezil 5 mg MRD: Cohort 11: TAK-071 9 mg + Donepezil 5 mg MRD: Cohort 12: TAK-071 15 mg+Donepezil 5 mg
Arm/Group Description TAK-071 3 mg capsules, orally, once daily along with donepezil 5 mg, tablets, orally, once daily from Day 1 up to Day 21 to non-Japanese healthy participants who were pre-treated with donepezil 5 mg, tablet, once daily for 3 weeks prior to administration of TAK-071. Dose of TAK-071 was same as the dose used in MRD Cohort 7. TAK-071 9 mg capsules, orally, once daily along with donepezil 5 mg, tablets, orally, once daily from Day 1 up to Day 21 to non-Japanese healthy participants who were pre-treated with donepezil 5 mg, tablet, once daily for 3 weeks prior to administration of TAK-071. Dose of TAK-071 was same as the dose used in MRD Cohort 8. TAK-071 15 mg capsule, orally, once daily along with donepezil 5 mg, tablets, orally, once daily from Day 1 up to Day 21 to non-Japanese healthy participants who were pre-treated with donepezil 5 mg, tablet, once daily for 3 weeks prior to administration of TAK-071. Dose of TAK-071 was same as the dose used in MRD Cohort 9.
Measure Participants 6 6 6
Mean (Standard Deviation) [Ratio]
2.929
(0.55096)
3.527
(0.57233)
3.257
(0.95527)
67. Secondary Outcome
Title AEt: Amount of Drug Excreted in Urine From Time 0 to Time t for TAK-071 SRD Non-Japanese Participants
Description
Time Frame Pre-dose on Day 1 and at multiple time points [up to 96 hours] post-dose

Outcome Measure Data

Analysis Population Description
PK set included all participants who received study drug and had at least 1 measurable plasma concentration or amount of drug in the urine. Measurable TAK-071 was not detected in urine for Cohort 1 (TAK-071 1 mg). Here, number analyzed is the number of participants with data available for analysis at the given time-point.
Arm/Group Title SRD: Cohort 2: TAK-071 3 mg SRD: Cohort 3: TAK-071 9 mg SRD: Cohort 4: TAK-071 20 mg SRD: Cohort 5: TAK-071 40 mg SRD: Cohort 6: TAK-071 80 mg SRD: Cohort 18: TAK-071 120 mg SRD: Cohort 19: TAK-071 160 mg
Arm/Group Description TAK-071 3 mg capsule, orally, once on Day 1 to non-Japanese healthy participants. Dose of TAK-071 was based on the 24-hour post-dose safety, tolerability and pharmacokinetic (PK) data from cohort 1. TAK-071 9 mg capsule, orally, once on Day 1 to non-Japanese healthy participants. Dose of TAK-071 was based on 24-hour safety, tolerability, and preliminary plasma PK and 12-hour CSF PK data. TAK-071 20 mg capsule, orally, once on Day 1 to non-Japanese healthy participants. Dose of TAK-071 was based on the 24-hour post-dose safety and tolerability data from previous cohort. TAK-071 40 mg capsule, orally, once on Day 1 to non-Japanese healthy participants. Dose of TAK-071 will be based on 24-hour safety, tolerability, and preliminary plasma PK data from Cohort 4. TAK-071 80 mg capsules, orally, once on Day 1 to non-Japanese healthy participants. Dose of TAK-071 was based on 24-hour safety, tolerability, and preliminary plasma PK data from Cohort 5 TAK-071 120 mg capsule, orally, once on Day 1 to non-Japanese healthy participants. Dose of TAK-071 was based on 24-hour safety, tolerability, and preliminary plasma PK data from Cohort 6. TAK-071 160 mg capsule, orally, once on Day 1 to non-Japanese healthy participants. Dose of TAK-071 was based on 24-hour safety, tolerability, and preliminary plasma PK data from Cohort 18.
Measure Participants 5 6 6 6 5 6 6
Mean (Standard Deviation) [mg]
0.001731
(0.0015806)
0.01632
(0.0062545)
0.05753
(0.023868)
0.08559
(0.052157)
0.09052
(0.044805)
0.1652
(0.097242)
0.1505
(0.10905)
68. Secondary Outcome
Title AEt: Amount of Drug Excreted in Urine From Time 0 to Time t for TAK-071 MRD Non-Japanese Participants
Description
Time Frame Pre-dose on Day 1 and 21 and at multiple time points (up to 24 hours) post-dose for Cohorts 7 and 8, and pre-dose on Day 1 and 28 and multiple time points (up to 96 hours) post-dose for Cohort 9

Outcome Measure Data

Analysis Population Description
PK set included all participants who received study drug and had at least 1 measurable plasma concentration or amount of drug in the urine. Here, number analyzed is the number of participants with data available for analysis at the given time-point.
Arm/Group Title MRD: Cohort 7: TAK-071 3 mg MRD: Cohort 8: TAK-071 9 mg MRD: Cohort 9: TAK-071 15 mg
Arm/Group Description TAK-071 3 mg capsules, orally, once daily from Day 1 up to Day 21 to non-Japanese healthy participants. Dose of TAK-071 was based on 24-hour safety and tolerability from Cohort 4 and the 24-hour preliminary plasma PK and 12-hour CSF PK data from Cohort 3. TAK-071 9 mg capsules, orally, once daily from Day 1 up to Day 21 to non-Japanese healthy participants. Dose of TAK-071 was based on safety, tolerability and available PK data arising from the ongoing SRD part and previous MRD cohort. TAK-071 15 mg capsule, orally, once on Day 1, followed by a washout period of 7 days, then TAK-071 once daily for 21 days to non-Japanese healthy participants. Dose of TAK-071 will be based on safety, tolerability and available PK data arising from the ongoing SRD part and previous MRD cohort.
Measure Participants 6 6 6
Day 1
0.001501
(0.0017987)
0.005973
(0.0034636)
0.04929
(0.019263)
Day 21
0.009066
(0.0042349)
0.02393
(0.014412)
Day 28
0.1119
(0.079021)
69. Secondary Outcome
Title AEt: Amount of Drug Excreted in Urine From Time 0 to Time t for TAK-071 MRD Japanese Participants
Description
Time Frame Pre-dose on Day 1 and at multiple time points (up to 96 hours) post-dose and pre-dose on Day 28 and multiple time points (up to 24 hours) post-dose

Outcome Measure Data

Analysis Population Description
PK set included all participants who received study drug and had at least 1 measurable plasma concentration or amount of drug in the urine.
Arm/Group Title MRD: Cohort 13: TAK-071 3 mg MRD: Cohort 14: TAK-071 9 mg MRD: Cohort 15: TAK-071 15 mg
Arm/Group Description TAK-071 3 mg capsule, orally, once on Day 1, followed by a washout period of 7 days, then TAK-071 once daily for 21 days to Japanese healthy participants. Dose of TAK-071 was same as the dose used in MRD Cohort 7. TAK-071 9 mg capsule or matching placebo, orally, once on Day 1, followed by a washout period of 7 days, then TAK-071 once daily for 21 days to Japanese healthy participants. Dose of TAK-071 was same as the dose used in MRD Cohort 8. TAK-071 15 mg capsule, orally, once on Day 1, followed by a washout period of 7 days, then TAK-071 once daily for 21 days to Japanese healthy participants. Dose of TAK-071 was same as the dose used in MRD Cohort 9.
Measure Participants 5 5 5
Day 1
0.003436
(0.0031125)
0.02083
(0.0094853)
0.03224
(0.023202)
Day 28
0.01202
(0.010480)
0.03394
(0.022682)
0.06482
(0.062816)
70. Secondary Outcome
Title Fet: Fraction of Administered Dose of Drug Excreted in Urine From Time 0 to Time t for TAK-071 SRD Non-Japanese Participants
Description
Time Frame Pre-dose on Day 1 and at multiple time points (up to 96 hours) post-dose

Outcome Measure Data

Analysis Population Description
PK set included all participants who received study drug and had at least 1 measurable plasma concentration or amount of drug in the urine. Measurable TAK-071 was not detected in urine for Cohort 1 (TAK-071 1 mg). Here, number analyzed is the number of participants with data available for analysis at the given time-point.
Arm/Group Title SRD: Cohort 2: TAK-071 3 mg SRD: Cohort 3: TAK-071 9 mg SRD: Cohort 4: TAK-071 20 mg SRD: Cohort 5: TAK-071 40 mg SRD: Cohort 6: TAK-071 80 mg SRD: Cohort 18: TAK-071 120 mg SRD: Cohort 19: TAK-071 160 mg
Arm/Group Description TAK-071 3 mg capsule, orally, once on Day 1 to non-Japanese healthy participants. Dose of TAK-071 was based on the 24-hour post-dose safety, tolerability and pharmacokinetic (PK) data from cohort 1. TAK-071 9 mg capsule, orally, once on Day 1 to non-Japanese healthy participants. Dose of TAK-071 was based on 24-hour safety, tolerability, and preliminary plasma PK and 12-hour CSF PK data. TAK-071 20 mg capsule, orally, once on Day 1 to non-Japanese healthy participants. Dose of TAK-071 was based on the 24-hour post-dose safety and tolerability data from previous cohort. TAK-071 40 mg capsule, orally, once on Day 1 to non-Japanese healthy participants. Dose of TAK-071 will be based on 24-hour safety, tolerability, and preliminary plasma PK data from Cohort 4. TAK-071 80 mg capsules, orally, once on Day 1 to non-Japanese healthy participants. Dose of TAK-071 was based on 24-hour safety, tolerability, and preliminary plasma PK data from Cohort 5 TAK-071 120 mg capsule, orally, once on Day 1 to non-Japanese healthy participants. Dose of TAK-071 was based on 24-hour safety, tolerability, and preliminary plasma PK data from Cohort 6. TAK-071 160 mg capsule, orally, once on Day 1 to non-Japanese healthy participants. Dose of TAK-071 was based on 24-hour safety, tolerability, and preliminary plasma PK data from Cohort 18.
Measure Participants 5 6 6 6 5 6 6
Mean (Standard Deviation) [fraction of drug excreted]
0.05771
(0.052687)
0.1813
(0.069494)
0.2877
(0.11934)
0.2140
(0.13039)
0.1131
(0.056006)
0.1377
(0.081035)
0.09408
(0.068159)
71. Secondary Outcome
Title Fet: Fraction of Administered Dose of Drug Excreted in Urine From Time 0 to Time t for TAK-071 MRD Non-Japanese Participants
Description
Time Frame Pre-dose on Days 1 and 21 and at multiple time points (up to 24 hours) post-dose for Cohorts 7 and 8 and Pre-dose on Days 1 and 28 and multiple time points (up to 96 hours) post-dose for Cohort 9

Outcome Measure Data

Analysis Population Description
PK set included all participants who received study drug and had at least 1 measurable plasma concentration or amount of drug in the urine. Here, number analyzed is the number of participants with data available for analysis at the given time-point.
Arm/Group Title MRD: Cohort 7: TAK-071 3 mg MRD: Cohort 8: TAK-071 9 mg MRD: Cohort 9: TAK-071 15 mg
Arm/Group Description TAK-071 3 mg capsules, orally, once daily from Day 1 up to Day 21 to non-Japanese healthy participants. Dose of TAK-071 was based on 24-hour safety and tolerability from Cohort 4 and the 24-hour preliminary plasma PK and 12-hour CSF PK data from Cohort 3. TAK-071 9 mg capsules, orally, once daily from Day 1 up to Day 21 to non-Japanese healthy participants. Dose of TAK-071 was based on safety, tolerability and available PK data arising from the ongoing SRD part and previous MRD cohort. TAK-071 15 mg capsule, orally, once on Day 1, followed by a washout period of 7 days, then TAK-071 once daily for 21 days to non-Japanese healthy participants. Dose of TAK-071 will be based on safety, tolerability and available PK data arising from the ongoing SRD part and previous MRD cohort.
Measure Participants 6 6 6
Day 1
0.05003
(0.059956)
0.06636
(0.038484)
0.3286
(0.12842)
Day 21
0.3022
(0.14116)
0.2659
(0.16013)
Day 28
0.7460
(0.52680)
72. Secondary Outcome
Title Fet: Fraction of Administered Dose of Drug Excreted in Urine From Time 0 to Time t for TAK-071 MRD Japanese Participants
Description
Time Frame Pre-dose on Day 1 and at multiple time points (up to 96 hours) post-dose and pre-dose on Day 28 and multiple time points (up to 24 hours) post-dose

Outcome Measure Data

Analysis Population Description
PK set included all participants who received study drug and had at least 1 measurable plasma concentration or amount of drug in the urine.
Arm/Group Title MRD: Cohort 13: TAK-071 3 mg MRD: Cohort 14: TAK-071 9 mg MRD: Cohort 15: TAK-071 15 mg
Arm/Group Description TAK-071 3 mg capsule, orally, once on Day 1, followed by a washout period of 7 days, then TAK-071 once daily for 21 days to Japanese healthy participants. Dose of TAK-071 was same as the dose used in MRD Cohort 7. TAK-071 9 mg capsule or matching placebo, orally, once on Day 1, followed by a washout period of 7 days, then TAK-071 once daily for 21 days to Japanese healthy participants. Dose of TAK-071 was same as the dose used in MRD Cohort 8. TAK-071 15 mg capsule, orally, once on Day 1, followed by a washout period of 7 days, then TAK-071 once daily for 21 days to Japanese healthy participants. Dose of TAK-071 was same as the dose used in MRD Cohort 9.
Measure Participants 5 5 5
Day 1
0.1145
(0.10375)
0.2314
(0.10539)
0.2150
(0.15468)
Day 28
0.4005
(0.34935)
0.3771
(0.25202)
0.4321
(0.41878)
73. Secondary Outcome
Title CLR: Renal Clearance for TAK-071 SRD Non-Japanese Participants
Description
Time Frame Pre-dose on Day 1 and at multiple time points [up to 96 hours] post-dose

Outcome Measure Data

Analysis Population Description
PK set included all participants who received study drug and had at least 1 measurable plasma concentration or amount of drug in the urine. Measurable TAK-071 was not detected in urine for Cohort 1 (TAK-071 1 mg). Here, number analyzed is the number of participants with data available for analysis at the given time-point.
Arm/Group Title SRD: Cohort 2: TAK-071 3 mg SRD: Cohort 3: TAK-071 9 mg SRD: Cohort 4: TAK-071 20 mg SRD: Cohort 5: TAK-071 40 mg SRD: Cohort 6: TAK-071 80 mg SRD: Cohort 18: TAK-071 120 mg SRD: Cohort 19: TAK-071 160 mg
Arm/Group Description TAK-071 3 mg capsule, orally, once on Day 1 to non-Japanese healthy participants. Dose of TAK-071 was based on the 24-hour post-dose safety, tolerability and pharmacokinetic (PK) data from cohort 1. TAK-071 9 mg capsule, orally, once on Day 1 to non-Japanese healthy participants. Dose of TAK-071 was based on 24-hour safety, tolerability, and preliminary plasma PK and 12-hour CSF PK data. TAK-071 20 mg capsule, orally, once on Day 1 to non-Japanese healthy participants. Dose of TAK-071 was based on the 24-hour post-dose safety and tolerability data from previous cohort. TAK-071 40 mg capsule, orally, once on Day 1 to non-Japanese healthy participants. Dose of TAK-071 will be based on 24-hour safety, tolerability, and preliminary plasma PK data from Cohort 4. TAK-071 80 mg capsules, orally, once on Day 1 to non-Japanese healthy participants. Dose of TAK-071 was based on 24-hour safety, tolerability, and preliminary plasma PK data from Cohort 5 TAK-071 120 mg capsule, orally, once on Day 1 to non-Japanese healthy participants. Dose of TAK-071 was based on 24-hour safety, tolerability, and preliminary plasma PK data from Cohort 6. TAK-071 160 mg capsule, orally, once on Day 1 to non-Japanese healthy participants. Dose of TAK-071 was based on 24-hour safety, tolerability, and preliminary plasma PK data from Cohort 18.
Measure Participants 5 6 6 6 5 6 6
Mean (Standard Deviation) [L/h]
0.0006354
(0.00072647)
0.001668
(0.00058267)
0.002775
(0.00098052)
0.002453
(0.0015795)
0.001425
(0.00071797)
0.001870
(0.0010016)
0.001696
(0.0015594)
74. Secondary Outcome
Title CLR: Renal Clearance for TAK-071 MRD Non-Japanese Participants
Description
Time Frame Pre-dose on Days 1 and 21 and at multiple time points (up to 24 hours) post-dose for Cohorts 7 and 8 and Pre-dose on Days 1 and 28 multiple time points (up to 96 hours) post-dose for Cohort 9

Outcome Measure Data

Analysis Population Description
PK set included all participants who received study drug and had at least 1 measurable plasma concentration or amount of drug in the urine. Here, number analyzed is the number of participants with data available for analysis at the given time-point.
Arm/Group Title MRD: Cohort 7: TAK-071 3 mg MRD: Cohort 8: TAK-071 9 mg MRD: Cohort 9: TAK-071 15 mg
Arm/Group Description TAK-071 3 mg capsules, orally, once daily from Day 1 up to Day 21 to non-Japanese healthy participants. Dose of TAK-071 was based on 24-hour safety and tolerability from Cohort 4 and the 24-hour preliminary plasma PK and 12-hour CSF PK data from Cohort 3. TAK-071 9 mg capsules, orally, once daily from Day 1 up to Day 21 to non-Japanese healthy participants. Dose of TAK-071 was based on safety, tolerability and available PK data arising from the ongoing SRD part and previous MRD cohort. TAK-071 15 mg capsule, orally, once on Day 1, followed by a washout period of 7 days, then TAK-071 once daily for 21 days to non-Japanese healthy participants. Dose of TAK-071 will be based on safety, tolerability and available PK data arising from the ongoing SRD part and previous MRD cohort.
Measure Participants 6 6 6
Day 1
0.001133
(0.0015553)
0.001686
(0.00092928)
0.003163
(0.0016448)
Day 21
0.001937
(0.00099073)
0.001991
(0.0012947)
Day 28
0.005431
(0.0032772)
75. Secondary Outcome
Title CLR: Renal Clearance for TAK-071 MRD Japanese Participants
Description
Time Frame Pre-dose on Day 1 and at multiple time points (up to 96 hours) post-dose and pre-dose on Day 28 and multiple time points (up to 24 hours) post-dose

Outcome Measure Data

Analysis Population Description
PK set included all participants who received study drug and had at least 1 measurable plasma concentration or amount of drug in the urine.
Arm/Group Title MRD: Cohort 13: TAK-071 3 mg MRD: Cohort 14: TAK-071 9 mg MRD: Cohort 15: TAK-071 15 mg
Arm/Group Description TAK-071 3 mg capsule, orally, once on Day 1, followed by a washout period of 7 days, then TAK-071 once daily for 21 days to Japanese healthy participants. Dose of TAK-071 was same as the dose used in MRD Cohort 7. TAK-071 9 mg capsule or matching placebo, orally, once on Day 1, followed by a washout period of 7 days, then TAK-071 once daily for 21 days to Japanese healthy participants. Dose of TAK-071 was same as the dose used in MRD Cohort 8. TAK-071 15 mg capsule, orally, once on Day 1, followed by a washout period of 7 days, then TAK-071 once daily for 21 days to Japanese healthy participants. Dose of TAK-071 was same as the dose used in MRD Cohort 9.
Measure Participants 5 5 5
Day 1
0.0008641
(0.00063849)
0.001783
(0.00090441)
0.002093
(0.0016105)
Day 28
0.002494
(0.0014594)
0.002680
(0.0019001)
0.003426
(0.0021244)
76. Secondary Outcome
Title CSF Cmax: Maximum Observed Concentration in Cerebrospinal Fluid (CSF) for TAK-071
Description
Time Frame Pre-dose on Day 1 and at multiple time points (up to 12 hours) post-dose

Outcome Measure Data

Analysis Population Description
PK set included all participants who received study drug and had at least 1 measurable plasma concentration or amount of drug in the urine.
Arm/Group Title SRD: Cohort 3: TAK-071 9 mg
Arm/Group Description TAK-071 9 mg capsule, orally, once on Day 1 to non-Japanese healthy participants. Dose of TAK-071 was based on 24-hour safety, tolerability, and preliminary plasma PK and 12-hour CSF PK data.
Measure Participants 6
Mean (Standard Deviation) [ng/mL]
0.008988
(0.0051582)
77. Secondary Outcome
Title CSF Cmax: Maximum Observed Concentration in Cerebrospinal Fluid (CSF) for TAK-071
Description
Time Frame Pre-dose on Day 28 and at multiple time points (up to 36 hours) post-dose

Outcome Measure Data

Analysis Population Description
PK set included all participants who received study drug and had at least 1 measurable plasma concentration or amount of drug in the urine. Here, number analyzed is the number of participants with data available for analysis at the given time-point.
Arm/Group Title MRD: Cohort 9: TAK-071 15 mg
Arm/Group Description TAK-071 15 mg capsule, orally, once on Day 1, followed by a washout period of 7 days, then TAK-071 once daily for 21 days to non-Japanese healthy participants. Dose of TAK-071 will be based on safety, tolerability and available PK data arising from the ongoing SRD part and previous MRD cohort.
Measure Participants 3
Mean (Standard Deviation) [ng/mL]
0.01144
(0.0012682)
78. Secondary Outcome
Title CSF AUC(0-12): Area Under the CSF Concentration-time Curve From Time 0 to 12 Hours for TAK-071
Description
Time Frame Pre-dose on Day 1 and at multiple time points (up to 12 hours) post-dose

Outcome Measure Data

Analysis Population Description
PK set included all participants who received study drug and had at least 1 measurable plasma concentration or amount of drug in the urine. Here, number analyzed is the number of participants with data available for analysis at the given time-point.
Arm/Group Title SRD: Cohort 3: TAK-071 9 mg
Arm/Group Description TAK-071 9 mg capsule, orally, once on Day 1 to non-Japanese healthy participants. Dose of TAK-071 was based on 24-hour safety, tolerability, and preliminary plasma PK and 12-hour CSF PK data.
Measure Participants 5
Mean (Standard Deviation) [h*ng/mL]
13.68
(3.9324)
79. Secondary Outcome
Title CSF AUC(0-36): Area Under the CSF Concentration-time Curve From Time 0 to 36 Hours for TAK-071
Description
Time Frame Pre-dose on Day 28 and multiple time points (up to 36 hours) post-dose

Outcome Measure Data

Analysis Population Description
PK set included all participants who received study drug and had at least 1 measurable plasma concentration or amount of drug in the urine. Here, number analyzed is the number of participants with data available for analysis at the given time-point.
Arm/Group Title MRD: Cohort 9: TAK-071 15 mg
Arm/Group Description TAK-071 15 mg capsule, orally, once on Day 1, followed by a washout period of 7 days, then TAK-071 once daily for 21 days to non-Japanese healthy participants. Dose of TAK-071 will be based on safety, tolerability and available PK data arising from the ongoing SRD part and previous MRD cohort.
Measure Participants 3
Mean (Standard Deviation) [h*ng/mL]
360.9
(73.780)
80. Secondary Outcome
Title Ratio of CSF AUC(0-12) to the Plasma AUC(0-12) for TAK-071
Description
Time Frame Pre-dose on Day 1 and at multiple time points [up to 168 hours] post-dose

Outcome Measure Data

Analysis Population Description
PK set included all participants who received study drug and had at least 1 measurable plasma concentration or amount of drug in the urine. Here, number analyzed is the number of participants with data available for analysis at the given time-point.
Arm/Group Title SRD: Cohort 3: TAK-071 9 mg
Arm/Group Description TAK-071 9 mg capsule, orally, once on Day 1 to non-Japanese healthy participants. Dose of TAK-071 was based on 24-hour safety, tolerability, and preliminary plasma PK and 12-hour CSF PK data.
Measure Participants 5
Mean (Standard Deviation) [Ratio]
0.009098
(0.0034530)
81. Secondary Outcome
Title Ratio of CSF AUC(0-36) to the Plasma AUC(0-36) for TAK-071
Description
Time Frame Pre-dose on Day 28 and multiple time points (up to 36 hours) post-dose Cohort 9

Outcome Measure Data

Analysis Population Description
PK set included all participants who received study drug and had at least 1 measurable plasma concentration or amount of drug in the urine. Here, number analyzed is the number of participants with data available for analysis at the given time-point.
Arm/Group Title MRD: Cohort 9: TAK-071 15 mg
Arm/Group Description TAK-071 15 mg capsule, orally, once on Day 1, followed by a washout period of 7 days, then TAK-071 once daily for 21 days to non-Japanese healthy participants. Dose of TAK-071 will be based on safety, tolerability and available PK data arising from the ongoing SRD part and previous MRD cohort.
Measure Participants 3
Mean (Standard Deviation) [Ratio]
0.01140
(0.0014959)
82. Secondary Outcome
Title Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Donepezil MRD Non-Japanese Participants
Description
Time Frame Pre-dose on Days -1 and 21 and multiple time points (up to 24 hours) post-dose

Outcome Measure Data

Analysis Population Description
PK set included all participants who received study drug and had at least 1 measurable plasma concentration or amount of drug in the urine.
Arm/Group Title MRD: Cohort 10: TAK-071 3 mg+Donepezil 5 mg MRD: Cohort 11: TAK-071 9 mg + Donepezil 5 mg MRD: Cohort 12: TAK-071 15 mg+Donepezil 5 mg
Arm/Group Description TAK-071 3 mg capsules, orally, once daily along with donepezil 5 mg, tablets, orally, once daily from Day 1 up to Day 21 to non-Japanese healthy participants who were pre-treated with donepezil 5 mg, tablet, once daily for 3 weeks prior to administration of TAK-071. Dose of TAK-071 was same as the dose used in MRD Cohort 7. TAK-071 9 mg capsules, orally, once daily along with donepezil 5 mg, tablets, orally, once daily from Day 1 up to Day 21 to non-Japanese healthy participants who were pre-treated with donepezil 5 mg, tablet, once daily for 3 weeks prior to administration of TAK-071. Dose of TAK-071 was same as the dose used in MRD Cohort 8. TAK-071 15 mg capsule, orally, once daily along with donepezil 5 mg, tablets, orally, once daily from Day 1 up to Day 21 to non-Japanese healthy participants who were pre-treated with donepezil 5 mg, tablet, once daily for 3 weeks prior to administration of TAK-071. Dose of TAK-071 was same as the dose used in MRD Cohort 9.
Measure Participants 6 6 6
Day -1
3.000
3.000
3.008
Day 21
2.508
3.500
2.500
83. Secondary Outcome
Title Cmax: Maximum Observed Plasma Concentration for Donepezil MRD Non-Japanese Participants
Description
Time Frame Pre-dose on Days -1 and 21 and multiple time points (up to 24 hours) post-dose

Outcome Measure Data

Analysis Population Description
PK set included all participants who received study drug and had at least 1 measurable plasma concentration or amount of drug in the urine.
Arm/Group Title MRD: Cohort 10: TAK-071 3 mg+Donepezil 5 mg MRD: Cohort 11: TAK-071 9 mg + Donepezil 5 mg MRD: Cohort 12: TAK-071 15 mg+Donepezil 5 mg
Arm/Group Description TAK-071 3 mg capsules, orally, once daily along with donepezil 5 mg, tablets, orally, once daily from Day 1 up to Day 21 to non-Japanese healthy participants who were pre-treated with donepezil 5 mg, tablet, once daily for 3 weeks prior to administration of TAK-071. Dose of TAK-071 was same as the dose used in MRD Cohort 7. TAK-071 9 mg capsules, orally, once daily along with donepezil 5 mg, tablets, orally, once daily from Day 1 up to Day 21 to non-Japanese healthy participants who were pre-treated with donepezil 5 mg, tablet, once daily for 3 weeks prior to administration of TAK-071. Dose of TAK-071 was same as the dose used in MRD Cohort 8. TAK-071 15 mg capsule, orally, once daily along with donepezil 5 mg, tablets, orally, once daily from Day 1 up to Day 21 to non-Japanese healthy participants who were pre-treated with donepezil 5 mg, tablet, once daily for 3 weeks prior to administration of TAK-071. Dose of TAK-071 was same as the dose used in MRD Cohort 9.
Measure Participants 6 6 6
Day -1
23.07
(3.6855)
30.65
(5.9433)
22.63
(4.2697)
Day 21
26.58
(2.3659)
29.95
(6.4071)
25.97
(5.6163)
84. Secondary Outcome
Title AUC(0-24): Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours Post-dose for Donepezil
Description
Time Frame Pre-dose on Days -1 and 21 and multiple time points (up to 24 hours) post-dose

Outcome Measure Data

Analysis Population Description
PK set included all participants who received study drug and had at least 1 measurable plasma concentration or amount of drug in the urine.
Arm/Group Title MRD: Cohort 10: TAK-071 3 mg+Donepezil 5 mg MRD: Cohort 11: TAK-071 9 mg + Donepezil 5 mg MRD: Cohort 12: TAK-071 15 mg+Donepezil 5 mg
Arm/Group Description TAK-071 3 mg capsules, orally, once daily along with donepezil 5 mg, tablets, orally, once daily from Day 1 up to Day 21 to non-Japanese healthy participants who were pre-treated with donepezil 5 mg, tablet, once daily for 3 weeks prior to administration of TAK-071. Dose of TAK-071 was same as the dose used in MRD Cohort 7. TAK-071 9 mg capsules, orally, once daily along with donepezil 5 mg, tablets, orally, once daily from Day 1 up to Day 21 to non-Japanese healthy participants who were pre-treated with donepezil 5 mg, tablet, once daily for 3 weeks prior to administration of TAK-071. Dose of TAK-071 was same as the dose used in MRD Cohort 8. TAK-071 15 mg capsule, orally, once daily along with donepezil 5 mg, tablets, orally, once daily from Day 1 up to Day 21 to non-Japanese healthy participants who were pre-treated with donepezil 5 mg, tablet, once daily for 3 weeks prior to administration of TAK-071. Dose of TAK-071 was same as the dose used in MRD Cohort 9.
Measure Participants 6 6 6
Day -1
410.1
(79.220)
543.8
(113.62)
399.5
(96.519)
Day 21
472.5
(62.377)
567.2
(135.33)
430.5
(111.93)
85. Secondary Outcome
Title Ratio of Geometric Mean of Cmax for Donepezil After 21 Daily Doses of TAK-071
Description A linear mixed effect model on the natural log-transformed parameters was performed with day as a fixed effect and participant as a random effect. Ratio is the exponentiated geometric mean value Day 21/Day -1 on the original scale.
Time Frame Pre-dose on Days -1 and 21 and multiple time points (up to 24 hours) post-dose

Outcome Measure Data

Analysis Population Description
PK set included all participants who received study drug and had at least 1 measurable plasma concentration or amount of drug in the urine. Here, number analyzed is the number of participants with data available for analysis at the given time-point.
Arm/Group Title MRD: Cohort 10: TAK-071 3 mg+Donepezil 5 mg MRD: Cohort 11: TAK-071 9 mg + Donepezil 5 mg MRD: Cohort 12: TAK-071 15 mg+Donepezil 5 mg
Arm/Group Description TAK-071 3 mg capsules, orally, once daily along with donepezil 5 mg, tablets, orally, once daily from Day 1 up to Day 21 to non-Japanese healthy participants who were pre-treated with donepezil 5 mg, tablet, once daily for 3 weeks prior to administration of TAK-071. Dose of TAK-071 was same as the dose used in MRD Cohort 7. TAK-071 9 mg capsules, orally, once daily along with donepezil 5 mg, tablets, orally, once daily from Day 1 up to Day 21 to non-Japanese healthy participants who were pre-treated with donepezil 5 mg, tablet, once daily for 3 weeks prior to administration of TAK-071. Dose of TAK-071 was same as the dose used in MRD Cohort 8. TAK-071 15 mg capsule, orally, once daily along with donepezil 5 mg, tablets, orally, once daily from Day 1 up to Day 21 to non-Japanese healthy participants who were pre-treated with donepezil 5 mg, tablet, once daily for 3 weeks prior to administration of TAK-071. Dose of TAK-071 was same as the dose used in MRD Cohort 9.
Measure Participants 8 8 8
Number (90% Confidence Interval) [Ratio]
1.160
0.969
1.121
86. Secondary Outcome
Title Ratio of Geometric Mean of AUC(0-24) for Donepezil After 21 Daily Doses of TAK-071
Description A linear mixed effect model on the natural log-transformed parameters was performed with day as a fixed effect and participant as a random effect. Ratio is the exponentiated geometric mean value Day 21/Day -1 on the original scale.
Time Frame Pre-dose on Days -1 and 21 and multiple time points (up to 24 hours) post-dose

Outcome Measure Data

Analysis Population Description
PK set included all participants who received study drug and had at least 1 measurable plasma concentration or amount of drug in the urine. Here, number analyzed is the number of participants with data available for analysis at the given time-point.
Arm/Group Title MRD: Cohort 10: TAK-071 3 mg+Donepezil 5 mg MRD: Cohort 11: TAK-071 9 mg + Donepezil 5 mg MRD: Cohort 12: TAK-071 15 mg+Donepezil 5 mg
Arm/Group Description TAK-071 3 mg capsules, orally, once daily along with donepezil 5 mg, tablets, orally, once daily from Day 1 up to Day 21 to non-Japanese healthy participants who were pre-treated with donepezil 5 mg, tablet, once daily for 3 weeks prior to administration of TAK-071. Dose of TAK-071 was same as the dose used in MRD Cohort 7. TAK-071 9 mg capsules, orally, once daily along with donepezil 5 mg, tablets, orally, once daily from Day 1 up to Day 21 to non-Japanese healthy participants who were pre-treated with donepezil 5 mg, tablet, once daily for 3 weeks prior to administration of TAK-071. Dose of TAK-071 was same as the dose used in MRD Cohort 8. TAK-071 15 mg capsule, orally, once daily along with donepezil 5 mg, tablets, orally, once daily from Day 1 up to Day 21 to non-Japanese healthy participants who were pre-treated with donepezil 5 mg, tablet, once daily for 3 weeks prior to administration of TAK-071. Dose of TAK-071 was same as the dose used in MRD Cohort 9.
Measure Participants 8 8 8
Number (90% Confidence Interval) [Ratio]
1.155
1.055
1.106

Adverse Events

Time Frame Day 1 up to Day 41
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 SRD: Placebo Cohorts 1-6, 18 and 19 SRD: Cohort 1: TAK-071 1 mg SRD: Cohort 2: TAK-071 3 mg SRD: Cohort 3: TAK-071 9 mg SRD: Cohort 4: TAK-071 20 mg SRD: Cohort 5: TAK-071 40 mg SRD: Cohort 6: TAK-071 80 mg MRD: Placebo Cohorts 7-9 MRD: Cohort 7: TAK-071 3 mg MRD: Cohort 8: TAK-071 9 mg MRD: Cohort 9: TAK-071 15 mg MRD: TAK-071 Placebo Cohorts 10-12+Donepezil MRD: Cohort 10: TAK-071 3 mg+Donepezil 5 mg MRD: Cohort 11: TAK-071 9 mg + Donepezil 5 mg MRD: Cohort 12: TAK-071 15 mg+Donepezil 5 mg MRD: Placebo Cohorts 13-15 MRD: Cohort 13: TAK-071 3 mg MRD: Cohort 14: TAK-071 9 mg MRD: Cohort 15: TAK-071 15 mg Cohort 16 Bioavailability (BA)/Food Effect: Cohort 17 Regimen A BA/Food Effect: Cohort 17 Regimen B BA/Food Effect: Cohort 17 Regimen C SRD: Cohort 18: TAK-071 120 mg SRD: Cohort 19: TAK-071 160 mg SRD: TAK-071 Placebo+Donepezil Placebo SRD: TAK-071 Placebo+Donepezil SRD: Cohort 20: TAK-071 40 mg+Donepezil SRD: Cohort 21: TAK-071 60 mg+Donepezil SRD: Cohort 22: TAK-071 80 mg+Donepezil
Arm/Group Description TAK-071 placebo-matching capsules, orally, once on Day 1 to non-Japanese healthy participants in the single-rising dose (SRD) period. TAK-071 1 mg, capsule, orally, once on Day 1 to non-Japanese healthy participants. TAK-071 3 mg capsule, orally, once on Day 1 to non-Japanese healthy participants. Dose of TAK-071 was based on the 24-hour post-dose safety, tolerability and pharmacokinetic (PK) data from cohort 1. TAK-071 9 mg capsule, orally, once on Day 1 to non-Japanese healthy participants. Dose of TAK-071 was based on 24-hour safety, tolerability, and preliminary plasma PK and 12-hour CSF PK data. TAK-071 20 mg capsule, orally, once on Day 1 to non-Japanese healthy participants. Dose of TAK-071 was based on the 24-hour post-dose safety and tolerability data from previous cohort. TAK-071 40 mg capsule, orally, once on Day 1 to non-Japanese healthy participants. Dose of TAK-071 will be based on 24-hour safety, tolerability, and preliminary plasma PK data from Cohort 4. TAK-071 80 mg capsules, orally, once on Day 1 to non-Japanese healthy participants. Dose of TAK-071 was based on 24-hour safety, tolerability, and preliminary plasma PK data from Cohort 5 TAK-071 placebo-matching capsule, orally, once on Day 1 to non-Japanese healthy participants in the multiple-rising dose (MRD) period. TAK-071 3 mg capsules, orally, once daily from Day 1 up to Day 21 to non-Japanese healthy participants. Dose of TAK-071 was based on 24-hour safety and tolerability from Cohort 4 and the 24-hour preliminary plasma PK and 12-hour CSF PK data from Cohort 3. TAK-071 9 mg capsules, orally, once daily from Day 1 up to Day 21 to non-Japanese healthy participants. Dose of TAK-071 was based on safety, tolerability and available PK data arising from the ongoing SRD part and previous MRD cohort. TAK-071 15 mg capsule, orally, once on Day 1, followed by a washout period of 7 days, then TAK-071 once daily for 21 days to non-Japanese healthy participants. Dose of TAK-071 will be based on safety, tolerability and available PK data arising from the ongoing SRD part and previous MRD cohort. TAK-071 placebo-matching capsule, orally, once daily along with donepezil 5 mg, tablets, orally, once daily from Day 1 up to Day 21 to non-Japanese healthy participants who were pre-treated with donepezil 5 mg, tablet, once daily for 3 weeks prior to administration of TAK-071. TAK-071 3 mg capsules, orally, once daily along with donepezil 5 mg, tablets, orally, once daily from Day 1 up to Day 21 to non-Japanese healthy participants who were pre-treated with donepezil 5 mg, tablet, once daily for 3 weeks prior to administration of TAK-071. Dose of TAK-071 was same as the dose used in MRD Cohort 7. TAK-071 9 mg capsules, orally, once daily along with donepezil 5 mg, tablets, orally, once daily from Day 1 up to Day 21 to non-Japanese healthy participants who were pre-treated with donepezil 5 mg, tablet, once daily for 3 weeks prior to administration of TAK-071. Dose of TAK-071 was same as the dose used in MRD Cohort 8. TAK-071 15 mg capsule, orally, once daily along with donepezil 5 mg, tablets, orally, once daily from Day 1 up to Day 21 to non-Japanese healthy participants who were pre-treated with donepezil 5 mg, tablet, once daily for 3 weeks prior to administration of TAK-071. Dose of TAK-071 was same as the dose used in MRD Cohort 9. TAK-071 placebo-matching capsule, orally, once on Day 1 to Japanese healthy participants. TAK-071 3 mg capsule, orally, once on Day 1, followed by a washout period of 7 days, then TAK-071 once daily for 21 days to Japanese healthy participants. Dose of TAK-071 was same as the dose used in MRD Cohort 7. TAK-071 9 mg capsule or matching placebo, orally, once on Day 1, followed by a washout period of 7 days, then TAK-071 once daily for 21 days to Japanese healthy participants. Dose of TAK-071 was same as the dose used in MRD Cohort 8. TAK-071 15 mg capsule, orally, once on Day 1, followed by a washout period of 7 days, then TAK-071 once daily for 21 days to Japanese healthy participants. Dose of TAK-071 was same as the dose used in MRD Cohort 9. TAK-071 capsule, orally, once on Day 1 for 21 days, followed by a washout period of 21 days, or placebo matching tablets, orally, once on Day 1 for 21 days. Donepezil was delivered as 5 mg tablet, orally, once followed by 10 mg tablet, orally, once in run-in period. TAK-071 10 mg capsule, orally once on Day 1 in the fasted state in Period 1 or Period 2 or Period 3 TAK-071 10 mg tablet, orally, once on Day 1 in the fasted state in Period 1 or Period 2 or Period 3 TAK-071 10 mg tablet, orally, once on Day 1 in the fed state in Period 1 or Period 2 or Period 3 TAK-071 120 mg capsule, orally, once on Day 1 to non-Japanese healthy participants. Dose of TAK-071 was based on 24-hour safety, tolerability, and preliminary plasma PK data from Cohort 6. TAK-071 160 mg capsule, orally, once on Day 1 to non-Japanese healthy participants. Dose of TAK-071 was based on 24-hour safety, tolerability, and preliminary plasma PK data from Cohort 18. TAK-071 placebo-matching capsule, orally, once on Day 1 followed by donepezil placebo-matching tablet, orally on Day 2 to non-Japanese healthy participants. TAK-071 placebo-matching capsule, orally, once on Day 1 followed by donepezil 10 mg tablet, orally, on Day 2 to non-Japanese healthy participants. TAK-071 40 mg capsule, orally, once on Day 1 followed by donepezil 10 mg, tablets, orally, once on Day 2 to non-Japanese healthy participants. Dose of TAK-071 was based on 24-hour safety, tolerability, and preliminary plasma PK data from Cohort 19. TAK-071 60 mg capsule, orally, once on Day 1 followed by donepezil 10 mg, tablets, orally, once on Day 2 to non-Japanese healthy participants. Dose of TAK-071 was based on 24-hour safety and tolerability data from Cohort 20. TAK-071 80 mg capsule, orally, once on Day 1, followed by donepezil 10 mg, tablets, orally, once on Day 2 to non-Japanese healthy participants. Dose of TAK-071 was based on 24-hour safety and tolerability data from Cohort 21.
All Cause Mortality
SRD: Placebo Cohorts 1-6, 18 and 19 SRD: Cohort 1: TAK-071 1 mg SRD: Cohort 2: TAK-071 3 mg SRD: Cohort 3: TAK-071 9 mg SRD: Cohort 4: TAK-071 20 mg SRD: Cohort 5: TAK-071 40 mg SRD: Cohort 6: TAK-071 80 mg MRD: Placebo Cohorts 7-9 MRD: Cohort 7: TAK-071 3 mg MRD: Cohort 8: TAK-071 9 mg MRD: Cohort 9: TAK-071 15 mg MRD: TAK-071 Placebo Cohorts 10-12+Donepezil MRD: Cohort 10: TAK-071 3 mg+Donepezil 5 mg MRD: Cohort 11: TAK-071 9 mg + Donepezil 5 mg MRD: Cohort 12: TAK-071 15 mg+Donepezil 5 mg MRD: Placebo Cohorts 13-15 MRD: Cohort 13: TAK-071 3 mg MRD: Cohort 14: TAK-071 9 mg MRD: Cohort 15: TAK-071 15 mg Cohort 16 Bioavailability (BA)/Food Effect: Cohort 17 Regimen A BA/Food Effect: Cohort 17 Regimen B BA/Food Effect: Cohort 17 Regimen C SRD: Cohort 18: TAK-071 120 mg SRD: Cohort 19: TAK-071 160 mg SRD: TAK-071 Placebo+Donepezil Placebo SRD: TAK-071 Placebo+Donepezil SRD: Cohort 20: TAK-071 40 mg+Donepezil SRD: Cohort 21: TAK-071 60 mg+Donepezil SRD: Cohort 22: TAK-071 80 mg+Donepezil
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 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 0/16 (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%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/3 (0%) 0/5 (0%) 0/5 (0%) 0/5 (0%) 0/0 (NaN) 0/12 (0%) 0/12 (0%) 0/12 (0%) 0/6 (0%) 0/6 (0%) 0/9 (0%) 0/9 (0%) 0/5 (0%) 0/6 (0%) 0/6 (0%)
Serious Adverse Events
SRD: Placebo Cohorts 1-6, 18 and 19 SRD: Cohort 1: TAK-071 1 mg SRD: Cohort 2: TAK-071 3 mg SRD: Cohort 3: TAK-071 9 mg SRD: Cohort 4: TAK-071 20 mg SRD: Cohort 5: TAK-071 40 mg SRD: Cohort 6: TAK-071 80 mg MRD: Placebo Cohorts 7-9 MRD: Cohort 7: TAK-071 3 mg MRD: Cohort 8: TAK-071 9 mg MRD: Cohort 9: TAK-071 15 mg MRD: TAK-071 Placebo Cohorts 10-12+Donepezil MRD: Cohort 10: TAK-071 3 mg+Donepezil 5 mg MRD: Cohort 11: TAK-071 9 mg + Donepezil 5 mg MRD: Cohort 12: TAK-071 15 mg+Donepezil 5 mg MRD: Placebo Cohorts 13-15 MRD: Cohort 13: TAK-071 3 mg MRD: Cohort 14: TAK-071 9 mg MRD: Cohort 15: TAK-071 15 mg Cohort 16 Bioavailability (BA)/Food Effect: Cohort 17 Regimen A BA/Food Effect: Cohort 17 Regimen B BA/Food Effect: Cohort 17 Regimen C SRD: Cohort 18: TAK-071 120 mg SRD: Cohort 19: TAK-071 160 mg SRD: TAK-071 Placebo+Donepezil Placebo SRD: TAK-071 Placebo+Donepezil SRD: Cohort 20: TAK-071 40 mg+Donepezil SRD: Cohort 21: TAK-071 60 mg+Donepezil SRD: Cohort 22: TAK-071 80 mg+Donepezil
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 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 0/16 (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%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/3 (0%) 0/5 (0%) 0/5 (0%) 0/5 (0%) 0/0 (NaN) 0/12 (0%) 0/12 (0%) 0/12 (0%) 0/6 (0%) 0/6 (0%) 0/9 (0%) 0/9 (0%) 0/5 (0%) 0/6 (0%) 0/6 (0%)
Other (Not Including Serious) Adverse Events
SRD: Placebo Cohorts 1-6, 18 and 19 SRD: Cohort 1: TAK-071 1 mg SRD: Cohort 2: TAK-071 3 mg SRD: Cohort 3: TAK-071 9 mg SRD: Cohort 4: TAK-071 20 mg SRD: Cohort 5: TAK-071 40 mg SRD: Cohort 6: TAK-071 80 mg MRD: Placebo Cohorts 7-9 MRD: Cohort 7: TAK-071 3 mg MRD: Cohort 8: TAK-071 9 mg MRD: Cohort 9: TAK-071 15 mg MRD: TAK-071 Placebo Cohorts 10-12+Donepezil MRD: Cohort 10: TAK-071 3 mg+Donepezil 5 mg MRD: Cohort 11: TAK-071 9 mg + Donepezil 5 mg MRD: Cohort 12: TAK-071 15 mg+Donepezil 5 mg MRD: Placebo Cohorts 13-15 MRD: Cohort 13: TAK-071 3 mg MRD: Cohort 14: TAK-071 9 mg MRD: Cohort 15: TAK-071 15 mg Cohort 16 Bioavailability (BA)/Food Effect: Cohort 17 Regimen A BA/Food Effect: Cohort 17 Regimen B BA/Food Effect: Cohort 17 Regimen C SRD: Cohort 18: TAK-071 120 mg SRD: Cohort 19: TAK-071 160 mg SRD: TAK-071 Placebo+Donepezil Placebo SRD: TAK-071 Placebo+Donepezil SRD: Cohort 20: TAK-071 40 mg+Donepezil SRD: Cohort 21: TAK-071 60 mg+Donepezil SRD: Cohort 22: TAK-071 80 mg+Donepezil
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 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 4/16 (25%) 2/6 (33.3%) 0/6 (0%) 4/6 (66.7%) 2/6 (33.3%) 0/6 (0%) 1/6 (16.7%) 3/6 (50%) 1/6 (16.7%) 1/6 (16.7%) 3/6 (50%) 2/6 (33.3%) 2/6 (33.3%) 3/6 (50%) 3/6 (50%) 2/3 (66.7%) 2/5 (40%) 2/5 (40%) 3/5 (60%) 0/0 (NaN) 2/12 (16.7%) 1/12 (8.3%) 1/12 (8.3%) 0/6 (0%) 2/6 (33.3%) 4/9 (44.4%) 5/9 (55.6%) 4/5 (80%) 6/6 (100%) 5/6 (83.3%)
Cardiac disorders
Palpitations 0/16 (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%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/3 (0%) 0/5 (0%) 0/5 (0%) 1/5 (20%) 0/0 (NaN) 0/12 (0%) 0/12 (0%) 0/12 (0%) 0/6 (0%) 0/6 (0%) 0/9 (0%) 0/9 (0%) 0/5 (0%) 0/6 (0%) 0/6 (0%)
Gastrointestinal disorders
Abdominal pain upper 1/16 (6.3%) 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%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 2/6 (33.3%) 1/6 (16.7%) 0/3 (0%) 0/5 (0%) 0/5 (0%) 1/5 (20%) 0/0 (NaN) 0/12 (0%) 0/12 (0%) 0/12 (0%) 0/6 (0%) 1/6 (16.7%) 0/9 (0%) 1/9 (11.1%) 0/5 (0%) 0/6 (0%) 1/6 (16.7%)
Diarrhoea 0/16 (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%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/3 (0%) 0/5 (0%) 0/5 (0%) 0/5 (0%) 0/0 (NaN) 0/12 (0%) 0/12 (0%) 0/12 (0%) 0/6 (0%) 1/6 (16.7%) 1/9 (11.1%) 1/9 (11.1%) 1/5 (20%) 0/6 (0%) 2/6 (33.3%)
Flatulence 1/16 (6.3%) 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%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/3 (0%) 0/5 (0%) 0/5 (0%) 0/5 (0%) 0/0 (NaN) 0/12 (0%) 0/12 (0%) 0/12 (0%) 0/6 (0%) 0/6 (0%) 0/9 (0%) 0/9 (0%) 0/5 (0%) 0/6 (0%) 0/6 (0%)
Constipation 1/16 (6.3%) 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%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/3 (0%) 0/5 (0%) 0/5 (0%) 0/5 (0%) 0/0 (NaN) 0/12 (0%) 0/12 (0%) 0/12 (0%) 0/6 (0%) 0/6 (0%) 0/9 (0%) 0/9 (0%) 0/5 (0%) 0/6 (0%) 0/6 (0%)
Nausea 0/16 (0%) 0/6 (0%) 0/6 (0%) 1/6 (16.7%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 1/6 (16.7%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 1/6 (16.7%) 1/6 (16.7%) 0/6 (0%) 0/6 (0%) 1/3 (33.3%) 0/5 (0%) 0/5 (0%) 0/5 (0%) 0/0 (NaN) 0/12 (0%) 0/12 (0%) 0/12 (0%) 0/6 (0%) 0/6 (0%) 0/9 (0%) 3/9 (33.3%) 2/5 (40%) 6/6 (100%) 4/6 (66.7%)
Sensitivity of teeth 0/16 (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%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/3 (0%) 0/5 (0%) 0/5 (0%) 0/5 (0%) 0/0 (NaN) 0/12 (0%) 0/12 (0%) 0/12 (0%) 0/6 (0%) 0/6 (0%) 0/9 (0%) 0/9 (0%) 0/5 (0%) 0/6 (0%) 0/6 (0%)
Vomiting 0/16 (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%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/3 (0%) 0/5 (0%) 0/5 (0%) 1/5 (20%) 0/0 (NaN) 0/12 (0%) 0/12 (0%) 0/12 (0%) 0/6 (0%) 0/6 (0%) 0/9 (0%) 0/9 (0%) 0/5 (0%) 4/6 (66.7%) 3/6 (50%)
Dyspepsia 0/16 (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%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/3 (0%) 0/5 (0%) 0/5 (0%) 0/5 (0%) 0/0 (NaN) 0/12 (0%) 0/12 (0%) 0/12 (0%) 0/6 (0%) 0/6 (0%) 0/9 (0%) 0/9 (0%) 0/5 (0%) 0/6 (0%) 0/6 (0%)
Abdominal pain 0/16 (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%) 0/6 (0%) 1/6 (16.7%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/3 (0%) 0/5 (0%) 0/5 (0%) 0/5 (0%) 0/0 (NaN) 0/12 (0%) 0/12 (0%) 0/12 (0%) 0/6 (0%) 0/6 (0%) 0/9 (0%) 0/9 (0%) 0/5 (0%) 0/6 (0%) 0/6 (0%)
Abdominal discomfort 0/16 (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%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/3 (0%) 0/5 (0%) 0/5 (0%) 1/5 (20%) 0/0 (NaN) 0/12 (0%) 0/12 (0%) 0/12 (0%) 0/6 (0%) 0/6 (0%) 0/9 (0%) 0/9 (0%) 0/5 (0%) 0/6 (0%) 0/6 (0%)
Frequent bowel movements 0/16 (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%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 1/3 (33.3%) 0/5 (0%) 0/5 (0%) 0/5 (0%) 0/0 (NaN) 0/12 (0%) 0/12 (0%) 0/12 (0%) 0/6 (0%) 0/6 (0%) 0/9 (0%) 0/9 (0%) 0/5 (0%) 0/6 (0%) 0/6 (0%)
Toothache 0/16 (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%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/3 (0%) 0/5 (0%) 0/5 (0%) 0/5 (0%) 0/0 (NaN) 1/12 (8.3%) 0/12 (0%) 0/12 (0%) 0/6 (0%) 0/6 (0%) 0/9 (0%) 0/9 (0%) 0/5 (0%) 0/6 (0%) 0/6 (0%)
General disorders
Fatigue 0/16 (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%) 0/6 (0%) 0/6 (0%) 1/6 (16.7%) 0/6 (0%) 0/6 (0%) 0/3 (0%) 0/5 (0%) 0/5 (0%) 0/5 (0%) 0/0 (NaN) 0/12 (0%) 0/12 (0%) 0/12 (0%) 0/6 (0%) 0/6 (0%) 0/9 (0%) 1/9 (11.1%) 0/5 (0%) 0/6 (0%) 0/6 (0%)
Puncture site pain 1/16 (6.3%) 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%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/3 (0%) 0/5 (0%) 0/5 (0%) 0/5 (0%) 0/0 (NaN) 0/12 (0%) 0/12 (0%) 0/12 (0%) 0/6 (0%) 0/6 (0%) 0/9 (0%) 0/9 (0%) 0/5 (0%) 0/6 (0%) 0/6 (0%)
Vessel puncture site bruise 0/16 (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%) 1/6 (16.7%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/3 (0%) 0/5 (0%) 0/5 (0%) 0/5 (0%) 0/0 (NaN) 0/12 (0%) 0/12 (0%) 0/12 (0%) 0/6 (0%) 0/6 (0%) 0/9 (0%) 0/9 (0%) 0/5 (0%) 0/6 (0%) 0/6 (0%)
Injection site haematoma 0/16 (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%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 1/6 (16.7%) 0/6 (0%) 0/3 (0%) 0/5 (0%) 0/5 (0%) 0/5 (0%) 0/0 (NaN) 0/12 (0%) 0/12 (0%) 0/12 (0%) 0/6 (0%) 0/6 (0%) 0/9 (0%) 0/9 (0%) 0/5 (0%) 0/6 (0%) 0/6 (0%)
Chills 0/16 (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%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/3 (0%) 0/5 (0%) 0/5 (0%) 1/5 (20%) 0/0 (NaN) 0/12 (0%) 0/12 (0%) 0/12 (0%) 0/6 (0%) 0/6 (0%) 0/9 (0%) 0/9 (0%) 0/5 (0%) 0/6 (0%) 0/6 (0%)
Pyrexia 0/16 (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%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/3 (0%) 0/5 (0%) 0/5 (0%) 1/5 (20%) 0/0 (NaN) 0/12 (0%) 0/12 (0%) 0/12 (0%) 0/6 (0%) 0/6 (0%) 0/9 (0%) 0/9 (0%) 0/5 (0%) 0/6 (0%) 0/6 (0%)
Influenza like illness 0/16 (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%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/3 (0%) 0/5 (0%) 0/5 (0%) 0/5 (0%) 0/0 (NaN) 0/12 (0%) 0/12 (0%) 0/12 (0%) 0/6 (0%) 0/6 (0%) 0/9 (0%) 0/9 (0%) 0/5 (0%) 0/6 (0%) 1/6 (16.7%)
Infections and infestations
Upper respiratory tract infection 0/16 (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%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/3 (0%) 0/5 (0%) 1/5 (20%) 0/5 (0%) 0/0 (NaN) 0/12 (0%) 0/12 (0%) 0/12 (0%) 0/6 (0%) 0/6 (0%) 0/9 (0%) 0/9 (0%) 0/5 (0%) 0/6 (0%) 0/6 (0%)
Injury, poisoning and procedural complications
Post lumbar puncture syndrome 1/16 (6.3%) 0/6 (0%) 0/6 (0%) 2/6 (33.3%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 1/6 (16.7%) 0/6 (0%) 0/6 (0%) 1/6 (16.7%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/3 (0%) 0/5 (0%) 0/5 (0%) 0/5 (0%) 0/0 (NaN) 0/12 (0%) 0/12 (0%) 0/12 (0%) 0/6 (0%) 0/6 (0%) 0/9 (0%) 0/9 (0%) 0/5 (0%) 0/6 (0%) 0/6 (0%)
Arthropod bite 0/16 (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%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/3 (0%) 0/5 (0%) 0/5 (0%) 0/5 (0%) 0/0 (NaN) 0/12 (0%) 0/12 (0%) 0/12 (0%) 0/6 (0%) 0/6 (0%) 0/9 (0%) 0/9 (0%) 0/5 (0%) 0/6 (0%) 0/6 (0%)
Laceration 1/16 (6.3%) 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%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/3 (0%) 0/5 (0%) 0/5 (0%) 1/5 (20%) 0/0 (NaN) 0/12 (0%) 0/12 (0%) 0/12 (0%) 0/6 (0%) 0/6 (0%) 0/9 (0%) 0/9 (0%) 0/5 (0%) 0/6 (0%) 0/6 (0%)
Procedural pain 0/16 (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%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/3 (0%) 0/5 (0%) 0/5 (0%) 0/5 (0%) 0/0 (NaN) 0/12 (0%) 0/12 (0%) 0/12 (0%) 0/6 (0%) 0/6 (0%) 0/9 (0%) 0/9 (0%) 0/5 (0%) 0/6 (0%) 0/6 (0%)
Investigations
Weight decreased 0/16 (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%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/3 (0%) 0/5 (0%) 0/5 (0%) 1/5 (20%) 0/0 (NaN) 0/12 (0%) 0/12 (0%) 0/12 (0%) 0/6 (0%) 0/6 (0%) 0/9 (0%) 0/9 (0%) 0/5 (0%) 0/6 (0%) 0/6 (0%)
Metabolism and nutrition disorders
Decreased appetite 0/16 (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%) 0/6 (0%) 1/6 (16.7%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/3 (0%) 0/5 (0%) 0/5 (0%) 1/5 (20%) 0/0 (NaN) 0/12 (0%) 0/12 (0%) 0/12 (0%) 0/6 (0%) 0/6 (0%) 0/9 (0%) 0/9 (0%) 0/5 (0%) 0/6 (0%) 0/6 (0%)
Musculoskeletal and connective tissue disorders
Back pain 0/16 (0%) 0/6 (0%) 0/6 (0%) 2/6 (33.3%) 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%) 0/6 (0%) 0/6 (0%) 0/3 (0%) 0/5 (0%) 1/5 (20%) 0/5 (0%) 0/0 (NaN) 0/12 (0%) 0/12 (0%) 0/12 (0%) 0/6 (0%) 1/6 (16.7%) 0/9 (0%) 0/9 (0%) 0/5 (0%) 0/6 (0%) 0/6 (0%)
Neck pain 0/16 (0%) 0/6 (0%) 0/6 (0%) 2/6 (33.3%) 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%) 0/6 (0%) 0/6 (0%) 0/3 (0%) 0/5 (0%) 0/5 (0%) 0/5 (0%) 0/0 (NaN) 0/12 (0%) 0/12 (0%) 0/12 (0%) 0/6 (0%) 0/6 (0%) 0/9 (0%) 0/9 (0%) 0/5 (0%) 0/6 (0%) 0/6 (0%)
Muscle spasms 0/16 (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%) 1/6 (16.7%) 1/6 (16.7%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/3 (0%) 0/5 (0%) 0/5 (0%) 0/5 (0%) 0/0 (NaN) 0/12 (0%) 0/12 (0%) 0/12 (0%) 0/6 (0%) 0/6 (0%) 0/9 (0%) 0/9 (0%) 0/5 (0%) 0/6 (0%) 0/6 (0%)
Musculoskeletal pain 0/16 (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%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 1/6 (16.7%) 0/3 (0%) 0/5 (0%) 0/5 (0%) 0/5 (0%) 0/0 (NaN) 0/12 (0%) 0/12 (0%) 0/12 (0%) 0/6 (0%) 0/6 (0%) 0/9 (0%) 0/9 (0%) 0/5 (0%) 0/6 (0%) 0/6 (0%)
Pain in extremity 0/16 (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%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 1/3 (33.3%) 0/5 (0%) 0/5 (0%) 0/5 (0%) 0/0 (NaN) 0/12 (0%) 0/12 (0%) 0/12 (0%) 0/6 (0%) 0/6 (0%) 0/9 (0%) 0/9 (0%) 0/5 (0%) 0/6 (0%) 0/6 (0%)
Nervous system disorders
Headache 0/16 (0%) 1/6 (16.7%) 0/6 (0%) 3/6 (50%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 2/6 (33.3%) 1/6 (16.7%) 0/6 (0%) 2/6 (33.3%) 0/6 (0%) 2/6 (33.3%) 1/6 (16.7%) 1/6 (16.7%) 0/3 (0%) 0/5 (0%) 1/5 (20%) 2/5 (40%) 0/0 (NaN) 0/12 (0%) 0/12 (0%) 0/12 (0%) 0/6 (0%) 0/6 (0%) 1/9 (11.1%) 0/9 (0%) 0/5 (0%) 1/6 (16.7%) 1/6 (16.7%)
Paraesthesia 1/16 (6.3%) 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%) 1/6 (16.7%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/3 (0%) 0/5 (0%) 0/5 (0%) 0/5 (0%) 0/0 (NaN) 0/12 (0%) 0/12 (0%) 0/12 (0%) 0/6 (0%) 0/6 (0%) 0/9 (0%) 0/9 (0%) 0/5 (0%) 0/6 (0%) 0/6 (0%)
Somnolence 0/16 (0%) 1/6 (16.7%) 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%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/3 (0%) 0/5 (0%) 0/5 (0%) 0/5 (0%) 0/0 (NaN) 0/12 (0%) 0/12 (0%) 0/12 (0%) 0/6 (0%) 0/6 (0%) 0/9 (0%) 0/9 (0%) 0/5 (0%) 0/6 (0%) 1/6 (16.7%)
Dizziness 0/16 (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%) 1/6 (16.7%) 1/6 (16.7%) 0/6 (0%) 1/6 (16.7%) 0/6 (0%) 0/3 (0%) 0/5 (0%) 0/5 (0%) 1/5 (20%) 0/0 (NaN) 0/12 (0%) 0/12 (0%) 0/12 (0%) 0/6 (0%) 0/6 (0%) 0/9 (0%) 0/9 (0%) 2/5 (40%) 0/6 (0%) 0/6 (0%)
Parosmia 0/16 (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%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 1/6 (16.7%) 0/3 (0%) 0/5 (0%) 0/5 (0%) 0/5 (0%) 0/0 (NaN) 0/12 (0%) 0/12 (0%) 0/12 (0%) 0/6 (0%) 0/6 (0%) 0/9 (0%) 0/9 (0%) 0/5 (0%) 0/6 (0%) 0/6 (0%)
Hypoaesthesia 0/16 (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%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/3 (0%) 0/5 (0%) 1/5 (20%) 0/5 (0%) 0/0 (NaN) 0/12 (0%) 0/12 (0%) 0/12 (0%) 0/6 (0%) 0/6 (0%) 0/9 (0%) 1/9 (11.1%) 0/5 (0%) 0/6 (0%) 0/6 (0%)
Syncope 0/16 (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%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/3 (0%) 0/5 (0%) 0/5 (0%) 0/5 (0%) 0/0 (NaN) 1/12 (8.3%) 0/12 (0%) 0/12 (0%) 0/6 (0%) 0/6 (0%) 0/9 (0%) 0/9 (0%) 0/5 (0%) 0/6 (0%) 0/6 (0%)
Psychiatric disorders
Irritability 0/16 (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%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/3 (0%) 0/5 (0%) 0/5 (0%) 1/5 (20%) 0/0 (NaN) 0/12 (0%) 0/12 (0%) 0/12 (0%) 0/6 (0%) 0/6 (0%) 0/9 (0%) 0/9 (0%) 0/5 (0%) 0/6 (0%) 0/6 (0%)
Abnormal dreams 0/16 (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%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/3 (0%) 0/5 (0%) 0/5 (0%) 0/5 (0%) 0/0 (NaN) 0/12 (0%) 0/12 (0%) 1/12 (8.3%) 0/6 (0%) 0/6 (0%) 0/9 (0%) 0/9 (0%) 0/5 (0%) 0/6 (0%) 0/6 (0%)
Insomnia 0/16 (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%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/3 (0%) 0/5 (0%) 0/5 (0%) 0/5 (0%) 0/0 (NaN) 0/12 (0%) 1/12 (8.3%) 0/12 (0%) 0/6 (0%) 0/6 (0%) 0/9 (0%) 0/9 (0%) 0/5 (0%) 0/6 (0%) 0/6 (0%)
Respiratory, thoracic and mediastinal disorders
Cough 0/16 (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%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 1/6 (16.7%) 0/3 (0%) 1/5 (20%) 0/5 (0%) 0/5 (0%) 0/0 (NaN) 0/12 (0%) 0/12 (0%) 0/12 (0%) 0/6 (0%) 0/6 (0%) 0/9 (0%) 0/9 (0%) 0/5 (0%) 0/6 (0%) 0/6 (0%)
Epistaxis 0/16 (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%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/3 (0%) 0/5 (0%) 1/5 (20%) 0/5 (0%) 0/0 (NaN) 0/12 (0%) 0/12 (0%) 0/12 (0%) 0/6 (0%) 0/6 (0%) 0/9 (0%) 0/9 (0%) 0/5 (0%) 0/6 (0%) 0/6 (0%)
Nasal congestion 0/16 (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%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/3 (0%) 1/5 (20%) 0/5 (0%) 0/5 (0%) 0/0 (NaN) 0/12 (0%) 0/12 (0%) 0/12 (0%) 0/6 (0%) 0/6 (0%) 1/9 (11.1%) 0/9 (0%) 0/5 (0%) 0/6 (0%) 0/6 (0%)
Sneezing 0/16 (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%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/3 (0%) 1/5 (20%) 0/5 (0%) 0/5 (0%) 0/0 (NaN) 0/12 (0%) 0/12 (0%) 0/12 (0%) 0/6 (0%) 0/6 (0%) 0/9 (0%) 0/9 (0%) 0/5 (0%) 0/6 (0%) 0/6 (0%)
Increased upper airway secretion 0/16 (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%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/3 (0%) 0/5 (0%) 0/5 (0%) 0/5 (0%) 0/0 (NaN) 0/12 (0%) 0/12 (0%) 0/12 (0%) 0/6 (0%) 0/6 (0%) 0/9 (0%) 0/9 (0%) 0/5 (0%) 0/6 (0%) 1/6 (16.7%)
Skin and subcutaneous tissue disorders
Pruritus 0/16 (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%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/3 (0%) 0/5 (0%) 0/5 (0%) 0/5 (0%) 0/0 (NaN) 0/12 (0%) 0/12 (0%) 0/12 (0%) 0/6 (0%) 1/6 (16.7%) 0/9 (0%) 0/9 (0%) 0/5 (0%) 0/6 (0%) 0/6 (0%)
Rash generalised 0/16 (0%) 0/6 (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%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/3 (0%) 0/5 (0%) 0/5 (0%) 0/5 (0%) 0/0 (NaN) 0/12 (0%) 0/12 (0%) 0/12 (0%) 0/6 (0%) 0/6 (0%) 0/9 (0%) 0/9 (0%) 0/5 (0%) 0/6 (0%) 0/6 (0%)
Rash 0/16 (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%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 1/6 (16.7%) 1/6 (16.7%) 0/3 (0%) 0/5 (0%) 1/5 (20%) 0/5 (0%) 0/0 (NaN) 0/12 (0%) 0/12 (0%) 0/12 (0%) 0/6 (0%) 0/6 (0%) 0/9 (0%) 0/9 (0%) 0/5 (0%) 0/6 (0%) 0/6 (0%)
Pruritus generalised 0/16 (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%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 1/6 (16.7%) 1/6 (16.7%) 0/3 (0%) 0/5 (0%) 0/5 (0%) 0/5 (0%) 0/0 (NaN) 0/12 (0%) 0/12 (0%) 0/12 (0%) 0/6 (0%) 0/6 (0%) 0/9 (0%) 0/9 (0%) 0/5 (0%) 0/6 (0%) 0/6 (0%)
Papule 0/16 (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%) 0/6 (0%) 0/6 (0%) 1/6 (16.7%) 0/6 (0%) 0/6 (0%) 0/3 (0%) 0/5 (0%) 0/5 (0%) 0/5 (0%) 0/0 (NaN) 0/12 (0%) 0/12 (0%) 0/12 (0%) 0/6 (0%) 0/6 (0%) 0/9 (0%) 0/9 (0%) 0/5 (0%) 0/6 (0%) 0/6 (0%)
Vascular disorders
Hot flush 0/16 (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%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/3 (0%) 0/5 (0%) 0/5 (0%) 0/5 (0%) 0/0 (NaN) 0/12 (0%) 0/12 (0%) 0/12 (0%) 0/6 (0%) 0/6 (0%) 1/9 (11.1%) 1/9 (11.1%) 0/5 (0%) 0/6 (0%) 1/6 (16.7%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The first study related publication will be a multi-center publication submitted within 24 months after conclusion or termination of a study at all sites. After such multi site publication, all proposed site publications and presentations will be submitted to sponsor for review 60 days in advance of publication. Site will remove Sponsor confidential information unrelated to study results. Sponsor can delay a proposed publication for another 60 days to preserve intellectual property.

Results Point of Contact

Name/Title Medical Director, Clinical Science
Organization Takeda
Phone +1-877-825-3327
Email trialdisclosures@takeda.com
Responsible Party:
Takeda
ClinicalTrials.gov Identifier:
NCT02769065
Other Study ID Numbers:
  • TAK-071-1001
  • U1111-1176-7435
First Posted:
May 11, 2016
Last Update Posted:
Jun 10, 2019
Last Verified:
Mar 1, 2019