A Study to Assess the Relative Bioavailability and to Ass... | NCT02480439

ID	Type	Description	Link
U1111-1170-0503	Registry Identifier	WHO

Description Module

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.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
TAK-648 Sequence ABC	Experimental	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 Drug: TAK-648 Oral Solution
TAK-648 Sequence BCA	Experimental	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 Drug: TAK-648 Oral Solution
TAK-648 Sequence CAB	Experimental	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 Drug: TAK-648 Oral Solution

Name	Type	Description	Arm Group Labels	Other Names
TAK-648 Tablet	Drug	Tak-648 tablet	TAK-648 Sequence ABC TAK-648 Sequence BCA TAK-648 Sequence CAB

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

Measure	Description	Time Frame
Percentage of Participants Who Experience at Least One Treatment Emergent Adverse Event (TEAE)	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.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Healthy male or female aged 18 to 55 years, inclusive, at the time of informed consent and first study medication dose.
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.
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.
Has a calculated creatinine clearance >60 milliliter per minute (mL/min) at Screening and Check-in (Day -1) of Period 1.
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.
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:

Has received any investigational compound within 30 days prior to the first dose of study medication.
Has received TAK-648 in a previous clinical study or as a therapeutic agent.
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.
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.
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.
Has diagnosis of major depression, bipolar disorder, or anxiety disorders, or has received any medication to treat any psychological disorders within 1 year.
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.
Has known hypersensitivity to any component of the formulation of TAK-648, or to a phosphodiesterase type 4 (PDE4) inhibitor (example, roflumilast).
Has taken any excluded medication, supplements, or food products during the time periods listed in the Prohibited Medications table.
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).

Name	Affiliation	Role
Medical Director	Takeda	Study Director

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	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.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Arm/Group Information

ID	Title	Description
BG000	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.
BG001	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.
BG002	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.
BG003	Total	Total of all reporting groups

Units	Counts
Participants	BG0008 BG0018 BG0028 BG00324

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Cmax: Maximum Observed Plasma Concentration for TAK-648

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

Posted

Mean

Standard Deviation

mg/mL

Day 1 pre-dose and multiple timepoints post-dose (Up to 72 hours) in each Period

ID	Title	Description
OG000	TAK-648 Regimen A	TAK-648 0.3 mg, tablet, orally, 30 minutes after a high fat meal, once on Day 1 of Period 1, 2 or 3.
OG001	TAK-648 Regimen B	Regimen B TAK-648 0.3 mg, tablet, orally, in fasted state, once on Day 1 of Period 1, 2 or 3.
OG002	TAK-648 Regimen C	Regimen C TAK-648 0.3 mg, solution, orally, in fasted state, once on Day 1 of Period 1, 2 or 3.

Units	Counts
Participants	OG00023 OG00123 OG00223

Title

Denominators

Categories

Title	Measurements
	OG0004.504± 1.2363 OG0014.707± 1.5255 OG0025.185± 1.9749

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001						Point Estimate	0.9660			2-Sided	90	0.8747	1.0668			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.	No	Superiority or Other
OG001 OG002

Primary

AUClast: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-648

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

Posted

Mean

Standard Deviation

ng*hr/mL

Day 1 pre-dose and multiple timepoints post-dose (Up to 72 hours) in each Period

ID	Title	Description
OG000	TAK-648 Regimen A	TAK-648 0.3 mg, tablet, orally, 30 minutes after a high fat meal, once on Day 1 of Period 1, 2 or 3.
OG001	TAK-648 Regimen B	Regimen B TAK-648 0.3 mg, tablet, orally, in fasted state, once on Day 1 of Period 1, 2 or 3.
OG002	TAK-648 Regimen C	Regimen C TAK-648 0.3 mg, solution, orally, in fasted state, once on Day 1 of Period 1, 2 or 3.

Units	Counts
Participants

Primary

AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-648

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

Posted

Mean

Standard Deviation

ng*hr/mL

Day 1 pre-dose and multiple timepoints post-dose (Up to 72 hours) in each Period

ID	Title	Description
OG000	TAK-648 Regimen A	TAK-648 0.3 mg, tablet, orally, 30 minutes after a high fat meal, once on Day 1 of Period 1, 2 or 3.
OG001	TAK-648 Regimen B	Regimen B TAK-648 0.3 mg, tablet, orally, in fasted state, once on Day 1 of Period 1, 2 or 3.
OG002	TAK-648 Regimen C	Regimen C TAK-648 0.3 mg, solution, orally, in fasted state, once on Day 1 of Period 1, 2 or 3.

Units	Counts
Participants

Secondary

Percentage of Participants Who Experience at Least One Treatment Emergent Adverse Event (TEAE)

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.

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

Posted

Number

percentage of participants

First dose of study drug to 30 days after the last dose of study drug (Up to Day 47)

ID	Title	Description
OG000	TAK-648 Regimen A	TAK-648 0.3 mg, tablet, orally, 30 minutes after a high fat meal, once on Day 1 of Period 1, 2 or 3.
OG001	TAK-648 Regimen B	Regimen B TAK-648 0.3 mg, tablet, orally, in fasted state, once on Day 1 of Period 1, 2 or 3.
OG002	TAK-648 Regimen C	Regimen C TAK-648 0.3 mg, solution, orally, in fasted state, once on Day 1 of Period 1, 2 or 3.

Secondary

Percentage of Participants With Markedly Abnormal Laboratory Values at Least Once Post-dose

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

Posted

Number

percentage of participants

First dose of study drug to 7 days after the last dose of study drug (Up to Day 24)

ID	Title	Description
OG000	TAK-648 Regimen A	TAK-648 0.3 mg, tablet, orally, 30 minutes after a high fat meal, once on Day 1 of Period 1, 2 or 3.
OG001	TAK-648 Regimen B	Regimen B TAK-648 0.3 mg, tablet, orally, in fasted state, once on Day 1 of Period 1, 2 or 3.
OG002	TAK-648 Regimen C	Regimen C TAK-648 0.3 mg, solution, orally, in fasted state, once on Day 1 of Period 1, 2 or 3.

Units	Counts
Participants

Secondary

Percentage of Participants With Markedly Abnormal Vital Sign Values at Least Once Post-dose

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

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

Posted

Number

percentage of participants

First dose of study drug to 7 days after the last dose of study drug (Up to Day 24)

ID	Title	Description
OG000	TAK-648 Regimen A	TAK-648 0.3 mg, tablet, orally, 30 minutes after a high fat meal, once on Day 1 of Period 1, 2 or 3.
OG001	TAK-648 Regimen B	Regimen B TAK-648 0.3 mg, tablet, orally, in fasted state, once on Day 1 of Period 1, 2 or 3.
OG002	TAK-648 Regimen C	Regimen C TAK-648 0.3 mg, solution, orally, in fasted state, once on Day 1 of Period 1, 2 or 3.

Units	Counts

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Blood creatine phosphokinase increased	Investigations	MedDRA 18.0	Systematic Assessment	EG0001 affected23 at risk EG0011 affected23 at risk EG0020 affected23 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected23 at risk EG0011 affected23 at risk EG0020 affected23 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected23 at risk EG0011 affected23 at risk EG0020 affected23 at risk
Headache	Nervous system disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected23 at risk EG0010 affected23 at risk EG0020 affected23 at risk
Heart rate irregular	Investigations	MedDRA 18.0	Systematic Assessment	EG0001 affected23 at risk EG0010 affected23 at risk EG0020 affected23 at risk
Limb injury	Injury, poisoning and procedural complications	MedDRA 18.0	Systematic Assessment	EG0001 affected23 at risk EG0010 affected23 at risk EG0020 affected23 at risk

ID	Title	Description	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	TAK-648 Regimen A	TAK-648 0.3 mg, tablet, orally, 30 minutes after a high fat meal, once on Day 1 of Period 1, 2 or 3.	23	4	23
EG001	TAK-648 Regimen B	Regimen B TAK-648 0.3 mg, tablet, orally, in fasted state, once on Day 1 of Period 1, 2 or 3.	23	2	23
EG002	TAK-648 Regimen C	Regimen C TAK-648 0.3 mg, solution, orally, in fasted state, once on Day 1 of Period 1, 2 or 3.	23	0	23