Healthy Volunteers
Conditions
Keywords
Drug Therapy
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.
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.
Interventions
DRUGTAK-648 Oral Solution
TAK-648 oral solution
DRUGTAK-648 Tablet
Tak-648 tablet
Sponsors
Takeda
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
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).
Design outcomes
Primary
| Measure | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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) | — |
| 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 \[bpm\]). |
Countries
United States
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 details
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).
Participants by arm
| Arm | Count |
|---|---|
| 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. | 8 |
| 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. | 8 |
| 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. | 8 |
| Total | 24 |
Baseline characteristics
| Characteristic | TAK-648 Sequence BCA | TAK-648 Sequence CAB | TAK-648 Sequence ABC | Total |
|---|---|---|---|---|
| Age, Continuous | 35.3 years STANDARD_DEVIATION 11 | 34.4 years STANDARD_DEVIATION 9.91 | 31.4 years STANDARD_DEVIATION 8.26 | 33.7 years STANDARD_DEVIATION 9.51 |
| Body Mass Index | 26.24 kg/m^2 STANDARD_DEVIATION 2.349 | 27.68 kg/m^2 STANDARD_DEVIATION 1.709 | 24.76 kg/m^2 STANDARD_DEVIATION 2.35 | 26.23 kg/m^2 STANDARD_DEVIATION 2.393 |
| Height | 163.4 cm STANDARD_DEVIATION 11.07 | 171.4 cm STANDARD_DEVIATION 4.98 | 175.6 cm STANDARD_DEVIATION 13.22 | 170.1 cm STANDARD_DEVIATION 11.18 |
| Race/Ethnicity, Customized Black or African American | 2 participants | 0 participants | 1 participants | 3 participants |
| Race/Ethnicity, Customized Hispanic or Latino | 6 participants | 3 participants | 4 participants | 13 participants |
| Race/Ethnicity, Customized Multiracial | 0 participants | 0 participants | 1 participants | 1 participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 2 participants | 5 participants | 4 participants | 11 participants |
| Race/Ethnicity, Customized White | 6 participants | 8 participants | 6 participants | 20 participants |
| Region of Enrollment United States | 8 participants | 8 participants | 8 participants | 24 participants |
| Sex: Female, Male Female | 5 Participants | 2 Participants | 2 Participants | 9 Participants |
| Sex: Female, Male Male | 3 Participants | 6 Participants | 6 Participants | 15 Participants |
| Weight | 70.11 kg STANDARD_DEVIATION 9.447 | 81.41 kg STANDARD_DEVIATION 7.596 | 77.46 kg STANDARD_DEVIATION 18.762 | 76.33 kg STANDARD_DEVIATION 13.219 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 4 / 23 | 2 / 23 | 0 / 23 |
| serious Total, serious adverse events | 0 / 23 | 0 / 23 | 0 / 23 |
Outcome results
Primary
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
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| TAK-648 Regimen A | AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-648 | 35.241 ng*hr/mL | Standard Deviation 8.9283 |
| TAK-648 Regimen B | AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-648 | 34.922 ng*hr/mL | Standard Deviation 9.3106 |
| TAK-648 Regimen C | AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-648 | 35.353 ng*hr/mL | Standard Deviation 10.7619 |
90% CI: [0.9541, 1.0464]
90% CI: [0.9676, 1.0612]
Primary
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
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| TAK-648 Regimen A | AUClast: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-648 | 34.855 ng*hr/mL | Standard Deviation 8.8481 |
| TAK-648 Regimen B | AUClast: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-648 | 34.526 ng*hr/mL | Standard Deviation 9.2767 |
| TAK-648 Regimen C | AUClast: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-648 | 34.916 ng*hr/mL | Standard Deviation 10.7221 |
90% CI: [0.954, 1.0477]
90% CI: [0.9685, 1.0636]
Primary
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
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| TAK-648 Regimen A | Cmax: Maximum Observed Plasma Concentration for TAK-648 | 4.504 mg/mL | Standard Deviation 1.2363 |
| TAK-648 Regimen B | Cmax: Maximum Observed Plasma Concentration for TAK-648 | 4.707 mg/mL | Standard Deviation 1.5255 |
| TAK-648 Regimen C | Cmax: Maximum Observed Plasma Concentration for TAK-648 | 5.185 mg/mL | Standard Deviation 1.9749 |
90% CI: [0.8747, 1.0668]
90% CI: [0.8352, 1.0185]
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.
Time frame: First dose of study drug to 30 days after the last dose of study drug (Up to Day 47)
Population: Safety Set included of all participants who were enrolled and received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TAK-648 Regimen A | Percentage of Participants Who Experience at Least One Treatment Emergent Adverse Event (TEAE) | 17.4 percentage of participants |
| TAK-648 Regimen B | Percentage of Participants Who Experience at Least One Treatment Emergent Adverse Event (TEAE) | 8.7 percentage of participants |
| TAK-648 Regimen C | Percentage of Participants Who Experience at Least One Treatment Emergent Adverse Event (TEAE) | 0.0 percentage of participants |
Secondary
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)
Population: Safety Set included of all participants who were enrolled and received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TAK-648 Regimen A | Percentage of Participants With Markedly Abnormal Laboratory Values at Least Once Post-dose | 4.3 percentage of participants |
| TAK-648 Regimen B | Percentage of Participants With Markedly Abnormal Laboratory Values at Least Once Post-dose | 4.3 percentage of participants |
| TAK-648 Regimen C | Percentage of Participants With Markedly Abnormal Laboratory Values at Least Once Post-dose | 0 percentage of 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 \[bpm\]).
Time frame: First dose of study drug to 7 days after the last dose of study drug (Up to Day 24)
Population: Safety Set included of all participants who were enrolled and received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TAK-648 Regimen A | Percentage of Participants With Markedly Abnormal Vital Sign Values at Least Once Post-dose | 39.1 percentage of participants |
| TAK-648 Regimen B | Percentage of Participants With Markedly Abnormal Vital Sign Values at Least Once Post-dose | 47.8 percentage of participants |
| TAK-648 Regimen C | Percentage of Participants With Markedly Abnormal Vital Sign Values at Least Once Post-dose | 60.9 percentage of participants |