A Study to Assess the Relative Bioavailability and to Assess the Effect of Food on the Bioavailability of a TAK-648 Tablet in Healthy Participants

• Sponsor: Takeda (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02480439
• Collaborator: (none)
• Enrollment: 24
• Location: 1
• Arms: 3
• Duration (Months): 3
• Patients Per Site Per Month: 7.9

Study Details

Study Description

Brief Summary

The purpose of this study is to assess the relative bioavailability of a TAK-648 tablet compared with a TAK-648 oral solution, and to assess the effect of food on the bioavailability of a TAK-648 tablet in healthy participants.

Condition or Disease	Intervention/Treatment	Phase
Healthy Volunteers	Drug: TAK-648 Tablet; Drug: TAK-648 Oral Solution	Phase 1

Detailed Description

This study will assess the relative Bioavailability (BA) of TAK-648 tablet compared with that of TAK-648 solution and the effect of food on the BA of the TAK-648 tablet.

The study will enroll approximately 24 healthy participants. Participants will be randomly assigned to one of the three treatment sequences:

• TAK-648 tablet in fed state, followed by TAK-648 tablet in fasted state, followed by TAK-648 oral solution in fasted state

• TAK-648 tablet in fasted state, followed by TAK-648 oral solution in fasted state, followed by TAK-648 tablet in fed state

• TAK-648 oral solution in fasted state, TAK-648 tablet in fed state, TAK-648 tablet in fasted state The dosing in a period and the subsequent period will be separated by a minimum 7-day washout interval. Participants will be asked to take single dose of TAK-648 tablet or oral solution on Day 1 of each period.

This single-center trial will be conducted in the United States. Participants will make 4 visits to the clinic including three 4-day periods of confinement to the clinic, and will be contacted by telephone 30 days after last dose of study drug for a follow-up assessment.

Study Design

• Study Type: Interventional
• Actual Enrollment: 24 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 1, Randomized, Open-Label, Single-Dose, 3-Way Crossover Study to Assess the Relative Bioavailability of a TAK-648 Tablet Compared With a TAK-648 Oral Solution, and to Assess the Effect of Food on the Bioavailability of a TAK-648 Tablet in Healthy Participants
• Study Start Date: Jun 1, 2015
• Actual Primary Completion Date: Aug 1, 2015
• Actual Study Completion Date: Sep 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: TAK-648 Sequence ABC Regimen A TAK-648 0.3 mg, tablet, orally, 30 minutes after a high fat meal, once on Day 1 of Period 1, followed by at least 7 day washout period, followed by Regimen B TAK-648 0.3 mg, tablet, orally, in fasted state, once on Day 1 of Period 2, followed by at least 7 day washout period, followed by Regimen C TAK-648 0.3 mg, solution, orally, in fasted state, once on Day 1 of Period 3.	Drug: TAK-648 Tablet; Tak-648 tablet; Drug: TAK-648 Oral Solution; TAK-648 oral solution
Experimental: TAK-648 Sequence BCA Regimen B TAK-648 0.3 mg, tablet, orally, in fasted state, once on Day 1 of Period 1, followed by at least 7 day washout period, followed by Regimen C TAK-648 0.3 mg, solution, orally, in fasted state, once on Day 1 of Period 2, followed by at least 7 day washout period, followed by Regimen A TAK-648 0.3 mg, tablet, orally, 30 minutes after a high fat meal, once on Day 1 of Period 3.	Drug: TAK-648 Tablet; Tak-648 tablet; Drug: TAK-648 Oral Solution; TAK-648 oral solution
Experimental: TAK-648 Sequence CAB Regimen C TAK-648 0.3 mg, solution, orally, in fasted state, once on Day 1 of Period 1, followed by at least 7 day washout period, followed by Regimen A TAK-648 0.3 mg, tablet, orally, after a high fat meal, once on Day 1 of Period 2, followed by at least 7 day washout period, followed by Regimen B TAK-648 0.3 mg, tablet, orally, in fasted state, once on Day 1 of Period 3.	Drug: TAK-648 Tablet; Tak-648 tablet; Drug: TAK-648 Oral Solution; TAK-648 oral solution

Outcome Measures

Primary Outcome Measures

1. Cmax: Maximum Observed Plasma Concentration for TAK-648 [Day 1 pre-dose and multiple timepoints post-dose (Up to 72 hours) in each Period]

2. AUClast: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-648 [Day 1 pre-dose and multiple timepoints post-dose (Up to 72 hours) in each Period]

3. AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-648 [Day 1 pre-dose and multiple timepoints post-dose (Up to 72 hours) in each Period]

Secondary Outcome Measures

1. Percentage of Participants Who Experience at Least One Treatment Emergent Adverse Event (TEAE) [First dose of study drug to 30 days after the last dose of study drug (Up to Day 47)]

   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 treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug.

2. Percentage of Participants With Markedly Abnormal Laboratory Values at Least Once Post-dose [First dose of study drug to 7 days after the last dose of study drug (Up to Day 24)]

3. Percentage of Participants With Markedly Abnormal Vital Sign Values at Least Once Post-dose [First dose of study drug to 7 days after the last dose of study drug (Up to Day 24)]

   Vital signs included body temperature (oral), sitting blood pressure (after 5 minutes resting), respiration rate and pulse (beats per minute [bpm]).

Eligibility Criteria

Criteria

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

Inclusion Criteria:

1. Healthy male or female aged 18 to 55 years, inclusive, at the time of informed consent and first study medication dose.

2. Weighs at least 50 kilogram (kg) (110 pounds [lbs]) and has a body mass index (BMI) from 18.0 to 30.0 kilogram per square meter (kg/m^2), inclusive at Screening.

3. Has systolic blood pressure greater than (>) 90 and less than or equal to (<=) 150 millimeter of mercury (mmHg) and diastolic blood pressure >60 and <=90 mm Hg at Screening and at Check-in (Day -1) of Period 1. If out of range, may be repeated once for eligibility determination within a maximum of 5 minutes.

4. Has a calculated creatinine clearance >60 milliliter per minute (mL/min) at Screening and Check-in (Day -1) of Period 1.

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

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

Exclusion Criteria:

1. Has received any investigational compound within 30 days prior to the first dose of study medication.

2. Has received TAK-648 in a previous clinical study or as a therapeutic agent.

3. Is an immediate family member, study site employee, or is in a dependent relationship with a study site employee who is involved in the conduct of this study (example, spouse, parent, child, sibling) or may consent under duress.

4. Has any significant medical histories or currently uncontrolled clinical conditions, which may render it unsafe for participant to participate in the study, may impact the ability of the participant to participate in the study, or may potentially confound the study results.

5. Has a history of significant gastrointestinal (GI) disorders manifested with persistent, chronic, or intermittent nausea, vomiting, or diarrhea, or has a current or recent (within 6 months) GI disease that would influence the absorption of drugs.

6. Has diagnosis of major depression, bipolar disorder, or anxiety disorders, or has received any medication to treat any psychological disorders within 1 year.

7. Has a risk of suicide according to the investigator's clinical judgment per Columbia-Suicide Severity Rating Scale (C-SSRS) at screening or has made a suicide attempt in the past 6 months prior to screening.

8. Has known hypersensitivity to any component of the formulation of TAK-648, or to a phosphodiesterase type 4 (PDE4) inhibitor (example, roflumilast).

9. Has taken any excluded medication, supplements, or food products during the time periods listed in the Prohibited Medications table.

10. Has abnormal Screening or Check-in (Day -1) of Period 1 laboratory values that suggest a clinically significant underlying disease or participant has the following laboratory abnormalities: Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) >2.5* upper limit of normal (ULN).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Austin	Texas	United States

Sponsors and Collaborators

• Takeda

Investigators

• Study Director: Medical Director, Takeda

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Takeda
• ClinicalTrials.gov Identifier: NCT02480439
• Other Study ID Numbers: TAK-648-1003; U1111-1170-0503
• First Posted: Jun 24, 2015
• Last Update Posted: Aug 31, 2016
• Last Verified: Jul 1, 2016

• Keywords provided by Takeda: Drug Therapy

Study Results

Participant Flow

Recruitment Details	Participants took part in the study at 1 investigative site in the United States from 23 June 2015 to 02 September 2015.
Pre-assignment Detail	Healthy participants were enrolled equally in 1 of 3 treatment sequences that determined the order of the three treatments received: TAK-648 0.3 mg tablet (fed), 0.3 mg tablet (fasted) and 0.3 mg solution (fasted).

Arm/Group Title	TAK-648 Sequence ABC	TAK-648 Sequence BCA	TAK-648 Sequence CAB
Arm/Group Description	Regimen A TAK-648 0.3 mg, tablet, orally, 30 minutes after a high fat meal, once on Day 1 of Period 1, followed by at least 7 day washout period, followed by Regimen B TAK-648 0.3 mg, tablet, orally, in fasted state, once on Day 1 of Period 2, followed by at least 7 day washout period, followed by Regimen C TAK-648 0.3 mg, solution, orally, in fasted state, once on Day 1 of Period 3.	Regimen B TAK-648 0.3 mg, tablet, orally, in fasted state, once on Day 1 of Period 1, followed by at least 7 day washout period, followed by Regimen C TAK-648 0.3 mg, solution, orally, in fasted state, once on Day 1 of Period 2, followed by at least 7 day washout period, followed by Regimen A TAK-648 0.3 mg, tablet, orally, 30 minutes after a high fat meal, once on Day 1 of Period 3.	Regimen C TAK-648 0.3 mg, solution, orally, in fasted state, once on Day 1 of Period 1, followed by at least 7 day washout period, followed by Regimen A TAK-648 0.3 mg, tablet, orally, after a high fat meal, once on Day 1 of Period 2, followed by at least 7 day washout period, followed by Regimen B TAK-648 0.3 mg, tablet, orally, in fasted state, once on Day 1 of Period 3.
Period Title: Treatment Period 1
STARTED	8	8	8
COMPLETED	8	8	8
NOT COMPLETED	0	0	0
Period Title: Treatment Period 1
STARTED	8	7	8
COMPLETED	8	7	8
NOT COMPLETED	0	0	0
Period Title: Treatment Period 1
STARTED	8	7	7
COMPLETED	8	7	7
NOT COMPLETED	0	0	0

Baseline Characteristics

Arm/Group Title	TAK-648 Sequence ABC	TAK-648 Sequence BCA	TAK-648 Sequence CAB	Total
Arm/Group Description	Regimen A TAK-648 0.3 mg, tablet, orally, 30 minutes after a high fat meal, once on Day 1 of Period 1, followed by at least 7 day washout period, followed by Regimen B TAK-648 0.3 mg, tablet, orally, in fasted state, once on Day 1 of Period 2, followed by at least 7 day washout period, followed by Regimen C TAK-648 0.3 mg, solution, orally, in fasted state, once on Day 1 of Period 3.	Regimen B TAK-648 0.3 mg, tablet, orally, in fasted state, once on Day 1 of Period 1, followed by at least 7 day washout period, followed by Regimen C TAK-648 0.3 mg, solution, orally, in fasted state, once on Day 1 of Period 2, followed by at least 7 day washout period, followed by Regimen A TAK-648 0.3 mg, tablet, orally, 30 minutes after a high fat meal, once on Day 1 of Period 3.	Regimen C TAK-648 0.3 mg, solution, orally, in fasted state, once on Day 1 of Period 1, followed by at least 7 day washout period, followed by Regimen A TAK-648 0.3 mg, tablet, orally, after a high fat meal, once on Day 1 of Period 2, followed by at least 7 day washout period, followed by Regimen B TAK-648 0.3 mg, tablet, orally, in fasted state, once on Day 1 of Period 3.	Total of all reporting groups
Overall Participants	8	8	8	24
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	31.4 (8.26)	35.3 (11.00)	34.4 (9.91)	33.7 (9.51)
Sex: Female, Male (Count of Participants)
Female	2 25%	5 62.5%	2 25%	9 37.5%
Male	6 75%	3 37.5%	6 75%	15 62.5%
Race/Ethnicity, Customized (participants) [Number]
Hispanic or Latino	4 50%	6 75%	3 37.5%	13 54.2%
Not Hispanic or Latino	4 50%	2 25%	5 62.5%	11 45.8%
Race/Ethnicity, Customized (participants) [Number]
Black or African American	1 12.5%	2 25%	0 0%	3 12.5%
White	6 75%	6 75%	8 100%	20 83.3%
Multiracial	1 12.5%	0 0%	0 0%	1 4.2%
Region of Enrollment (participants) [Number]
United States	8 100%	8 100%	8 100%	24 100%
Height (cm) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [cm]	175.6 (13.22)	163.4 (11.07)	171.4 (4.98)	170.1 (11.18)
Weight (kg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg]	77.46 (18.762)	70.11 (9.447)	81.41 (7.596)	76.33 (13.219)
Body Mass Index (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	24.76 (2.350)	26.24 (2.349)	27.68 (1.709)	26.23 (2.393)

Outcome Measures

1. Primary Outcome

Title	Cmax: Maximum Observed Plasma Concentration for TAK-648
Time Frame	Day 1 pre-dose and multiple timepoints post-dose (Up to 72 hours) in each Period

Outcome Measure Data

Analysis Population Description

The PK Set included all participants who received at least 1 dose of study drug and had at least 1 measurable postdose plasma concentration.

Arm/Group Title	TAK-648 Regimen A	TAK-648 Regimen B	TAK-648 Regimen C
Arm/Group Description	TAK-648 0.3 mg, tablet, orally, 30 minutes after a high fat meal, once on Day 1 of Period 1, 2 or 3.	Regimen B TAK-648 0.3 mg, tablet, orally, in fasted state, once on Day 1 of Period 1, 2 or 3.	Regimen C TAK-648 0.3 mg, solution, orally, in fasted state, once on Day 1 of Period 1, 2 or 3.
Measure Participants	23	23	23
Mean (Standard Deviation) [mg/mL]	4.504 (1.2363)	4.707 (1.5255)	5.185 (1.9749)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	TAK-648 Regimen A, TAK-648 Regimen B
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Point Estimate
	Estimated Value	0.9660
	Confidence Interval	(2-Sided) 90%; 0.8747 to 1.0668
	Parameter Dispersion	Type: Value:
	Estimation Comments	Relative Bioavailability A/B. The point estimates and 90% CIs were obtained from the exponentiated results of the analysis of the natural logarithm-transformed data.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	TAK-648 Regimen B, TAK-648 Regimen C
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Point Estimate
	Estimated Value	0.9223
	Confidence Interval	(2-Sided) 90%; 0.8352 to 1.0185
	Parameter Dispersion	Type: Value:
	Estimation Comments	Relative Bioavailability B/C. The point estimates and 90% CIs were obtained from the exponentiated results of the analysis of the natural logarithm-transformed data.

2. Primary Outcome

Title	AUClast: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-648
Time Frame	Day 1 pre-dose and multiple timepoints post-dose (Up to 72 hours) in each Period

Outcome Measure Data

Analysis Population Description

The PK Set included all participants who received at least 1 dose of study drug and had at least 1 measurable postdose plasma concentration.

Arm/Group Title	TAK-648 Regimen A	TAK-648 Regimen B	TAK-648 Regimen C
Arm/Group Description	TAK-648 0.3 mg, tablet, orally, 30 minutes after a high fat meal, once on Day 1 of Period 1, 2 or 3.	Regimen B TAK-648 0.3 mg, tablet, orally, in fasted state, once on Day 1 of Period 1, 2 or 3.	Regimen C TAK-648 0.3 mg, solution, orally, in fasted state, once on Day 1 of Period 1, 2 or 3.
Measure Participants	23	23	23
Mean (Standard Deviation) [ng*hr/mL]	34.855 (8.8481)	34.526 (9.2767)	34.916 (10.7221)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	TAK-648 Regimen A, TAK-648 Regimen B
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Point Estimate
	Estimated Value	0.9998
	Confidence Interval	(2-Sided) 90%; 0.9540 to 1.0477
	Parameter Dispersion	Type: Value:
	Estimation Comments	Relative Bioavailability A/B. The point estimates and 90% CIs were obtained from the exponentiated results of the analysis of the natural logarithm-transformed data.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	TAK-648 Regimen B, TAK-648 Regimen C
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Point Estimate
	Estimated Value	1.0149
	Confidence Interval	(2-Sided) 90%; 0.9685 to 1.0636
	Parameter Dispersion	Type: Value:
	Estimation Comments	Relative Bioavailability B/C. The point estimates and 90% CIs were obtained from the exponentiated results of the analysis of the natural logarithm-transformed data.

3. Primary Outcome

Title	AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-648
Time Frame	Day 1 pre-dose and multiple timepoints post-dose (Up to 72 hours) in each Period

Outcome Measure Data

Analysis Population Description

The PK Set included all participants who received at least 1 dose of study drug and had at least 1 measurable postdose plasma concentration.

Arm/Group Title	TAK-648 Regimen A	TAK-648 Regimen B	TAK-648 Regimen C
Arm/Group Description	TAK-648 0.3 mg, tablet, orally, 30 minutes after a high fat meal, once on Day 1 of Period 1, 2 or 3.	Regimen B TAK-648 0.3 mg, tablet, orally, in fasted state, once on Day 1 of Period 1, 2 or 3.	Regimen C TAK-648 0.3 mg, solution, orally, in fasted state, once on Day 1 of Period 1, 2 or 3.
Measure Participants	23	23	23
Mean (Standard Deviation) [ng*hr/mL]	35.241 (8.9283)	34.922 (9.3106)	35.353 (10.7619)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	TAK-648 Regimen A, TAK-648 Regimen B
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Point Estimate
	Estimated Value	0.9992
	Confidence Interval	(2-Sided) 90%; 0.9541 to 1.0464
	Parameter Dispersion	Type: Value:
	Estimation Comments	Relative Bioavailability A/B. The point estimates and 90% CIs were obtained from the exponentiated results of the analysis of the natural logarithm-transformed data.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	TAK-648 Regimen B, TAK-648 Regimen C
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Point Estimate
	Estimated Value	1.0134
	Confidence Interval	(2-Sided) 90%; 0.9676 to 1.0612
	Parameter Dispersion	Type: Value:
	Estimation Comments	Relative Bioavailability B/C. The point estimates and 90% CIs were obtained from the exponentiated results of the analysis of the natural logarithm-transformed data.

4. Secondary Outcome

Title	Percentage of Participants Who Experience 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 treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug.
Time Frame	First dose of study drug to 30 days after the last dose of study drug (Up to Day 47)

Outcome Measure Data

Analysis Population Description

Safety Set included of all participants who were enrolled and received at least 1 dose of study drug.

Arm/Group Title	TAK-648 Regimen A	TAK-648 Regimen B	TAK-648 Regimen C
Arm/Group Description	TAK-648 0.3 mg, tablet, orally, 30 minutes after a high fat meal, once on Day 1 of Period 1, 2 or 3.	Regimen B TAK-648 0.3 mg, tablet, orally, in fasted state, once on Day 1 of Period 1, 2 or 3.	Regimen C TAK-648 0.3 mg, solution, orally, in fasted state, once on Day 1 of Period 1, 2 or 3.
Measure Participants	23	23	23
Number [percentage of participants]	17.4 217.5%	8.7 108.8%	0.0 0%

5. Secondary Outcome

Title	Percentage of Participants With Markedly Abnormal Laboratory Values at Least Once Post-dose
Time Frame	First dose of study drug to 7 days after the last dose of study drug (Up to Day 24)

Outcome Measure Data

Analysis Population Description

Safety Set included of all participants who were enrolled and received at least 1 dose of study drug.

Arm/Group Title	TAK-648 Regimen A	TAK-648 Regimen B	TAK-648 Regimen C
Arm/Group Description	TAK-648 0.3 mg, tablet, orally, 30 minutes after a high fat meal, once on Day 1 of Period 1, 2 or 3.	Regimen B TAK-648 0.3 mg, tablet, orally, in fasted state, once on Day 1 of Period 1, 2 or 3.	Regimen C TAK-648 0.3 mg, solution, orally, in fasted state, once on Day 1 of Period 1, 2 or 3.
Measure Participants	23	23	23
Number [percentage of participants]	4.3 53.8%	4.3 53.8%	0 0%

6. Secondary Outcome

Title	Percentage of Participants With Markedly Abnormal Vital Sign Values at Least Once Post-dose
Description	Vital signs included body temperature (oral), sitting blood pressure (after 5 minutes resting), respiration rate and pulse (beats per minute [bpm]).
Time Frame	First dose of study drug to 7 days after the last dose of study drug (Up to Day 24)

Outcome Measure Data

Analysis Population Description

Safety Set included of all participants who were enrolled and received at least 1 dose of study drug.

Arm/Group Title	TAK-648 Regimen A	TAK-648 Regimen B	TAK-648 Regimen C
Arm/Group Description	TAK-648 0.3 mg, tablet, orally, 30 minutes after a high fat meal, once on Day 1 of Period 1, 2 or 3.	Regimen B TAK-648 0.3 mg, tablet, orally, in fasted state, once on Day 1 of Period 1, 2 or 3.	Regimen C TAK-648 0.3 mg, solution, orally, in fasted state, once on Day 1 of Period 1, 2 or 3.
Measure Participants	23	23	23
Number [percentage of participants]	39.1 488.8%	47.8 597.5%	60.9 761.3%

Adverse Events

Time Frame	First dose of study drug to 30 days after last dose (Up to Day 47)
Adverse Event Reporting Description	At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Arm/Group Title	TAK-648 Regimen A		TAK-648 Regimen B		TAK-648 Regimen C
Arm/Group Description	TAK-648 0.3 mg, tablet, orally, 30 minutes after a high fat meal, once on Day 1 of Period 1, 2 or 3.		Regimen B TAK-648 0.3 mg, tablet, orally, in fasted state, once on Day 1 of Period 1, 2 or 3.		Regimen C TAK-648 0.3 mg, solution, orally, in fasted state, once on Day 1 of Period 1, 2 or 3.
All Cause Mortality
	TAK-648 Regimen A		TAK-648 Regimen B		TAK-648 Regimen C
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	TAK-648 Regimen A		TAK-648 Regimen B		TAK-648 Regimen C
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/23 (0%)		0/23 (0%)		0/23 (0%)
Other (Not Including Serious) Adverse Events
	TAK-648 Regimen A		TAK-648 Regimen B		TAK-648 Regimen C
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/23 (17.4%)		2/23 (8.7%)		0/23 (0%)
Gastrointestinal disorders
Abdominal pain	1/23 (4.3%)		1/23 (4.3%)		0/23 (0%)
Injury, poisoning and procedural complications
Limb injury	1/23 (4.3%)		0/23 (0%)		0/23 (0%)
Investigations
Blood creatine phosphokinase increased	1/23 (4.3%)		1/23 (4.3%)		0/23 (0%)
Heart rate irregular	1/23 (4.3%)		0/23 (0%)		0/23 (0%)
Nervous system disorders
Headache	1/23 (4.3%)		0/23 (0%)		0/23 (0%)
Respiratory, thoracic and mediastinal disorders
Cough	0/23 (0%)		1/23 (4.3%)		0/23 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

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