Healthy Volunteers
Conditions
Keywords
Drug Therapy
Brief summary
The purpose of this study is to assess the oral BA of TAK-831 T3 tablet formulation relative to TAK-831 T2 tablet formulation under fasting conditions and to assess the effect of food on the pharmacokinetics (PK) of TAK-831 T3 tablet formulation.
Detailed description
The drug being tested in this study is called TAK-831. TAK-831 is being tested in healthy participants to evaluate the relative BA and effect of food on the PK of TAK-831 tablet formulation. The study will enroll approximately 16 participants. Participants will be randomly assigned (by chance, like flipping a coin) to TAK-831 in 1 of the 4 treatment sequences as following: * T2 50 mg Fasted + T3 50 mg Fasted + T3 600 mg Fasted + T2 600 mg Fasted + T3 600 mg Fed * T3 50 mg Fasted + T2 600 mg Fasted + T2 50 mg Fasted + T3 600 mg Fasted + T3 600 mg Fed * T2 600 mg Fasted + T3 600 mg Fasted + T3 50 mg Fasted + T2 50 mg Fasted + T3 600 mg Fed * T3 600 mg Fasted + T2 50 mg Fasted + T2 600 mg Fasted + T3 50 mg Fasted + T3 600 mg Fed All participants will be asked to take tablet of assigned TAK-831 on Day 1 of each treatment period. This single center trial will be conducted in the United States. The overall time to participate in this study is approximately 70 days. Participants will make multiple visits to the clinic and will be contacted by clinic approximately 14 days after the last dose of study drug for a follow-up assessment.
Interventions
DRUGTAK-831 T2
TAK-831 T2 Tablets.
DRUGTAK-831 T3
TAK-831 T3 Tablets.
Sponsors
Takeda
Neurocrine Biosciences
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
19 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
1\. Body mass index (BMI) greater than or equal to (\>=) 18.0 and less than (\<) 30.0 kilogram per square meter (kg/m\^2), at Screening.
Exclusion criteria
1. History or presence of alcoholism or drug abuse within the past 2 years prior to the first dosing. 2. Smokes more than 20 cigarettes or equivalent per day within 3 months prior to the first dose and is unwilling to discontinue use of any tobacco- or nicotine-containing products during the confinement period(s) of the study. 3. Has been on a diet incompatible with the on-study diet, in the opinion of the Investigator or designee, within the 30 days prior to the first dosing and throughout the study. 4. Is lactose intolerant or unable/unwilling to eat the high-fat breakfast. 5. Donation of blood or significant blood loss within 56 days prior to the first dosing.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-831 | Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose |
| AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-831 | Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose |
| Cmax: Maximum Observed Plasma Concentration for TAK-831 | Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose |
Secondary
| Measure | Time frame |
|---|---|
| Percentage of Participants Who Experience at Least One Treatment Emergent Adverse Event (TEAE) | Day 1 post dose up to 14 days after the last dose of study drug (Up to Day 47) |
Countries
United States
Participant flow
Recruitment details
Participants took part in the study at 1 investigative site in the United States from 18 October 2018 to 22 December 2018.
Pre-assignment details
Healthy participants were enrolled and randomized in one of the 4 treatment sequences to receive TAK-831.
Participants by arm
| Arm | Count |
|---|---|
| Fasted (T2 50 mg+T3 50 mg+T3 600 mg+T2 600 mg)+Fed (T3 600 mg) TAK-831 T2 50 mg, tablet, orally, once, under fasted condition on Day 1 of Treatment Period 1, followed by TAK-831 T3 50 mg, tablet, orally, once, under fasted condition on Day 1 of Treatment Period 2, followed by TAK-831 T3 600 mg, tablet, orally, once, under fasted condition on Day 1 of Treatment Period 3, followed by TAK-831 T2 600 mg, tablet, orally, once, under fasted condition on Day 1 of Treatment Period 4, further followed by TAK-831 T3 600 mg, tablet, orally, once, under fed condition on Day 1 of Treatment Period 5. There was a washout period of at least 7 days between study drug in-take in subsequent treatment periods. | 4 |
| Fasted (T3 50 mg+T2 600 mg+T2 50 mg+T3 600 mg)+Fed (T3 600 mg) TAK-831 T3 50 mg, tablet, orally, once, under fasted condition on Day 1 of Treatment Period 1, followed by TAK-831 T2 600 mg, tablet, orally, once, under fasted condition on Day 1 of Treatment Period 2, followed by TAK-831 T2 50 mg, tablet, orally, once, under fasted condition on Day 1 of Treatment Period 3, followed by TAK-831 T3 600 mg, tablet, orally, once, under fasted condition on Day 1 of Treatment Period 4, further followed by TAK-831 T3 600 mg, tablet, orally, once, under fed condition on Day 1 of Treatment Period 5. There was a washout period of at least 7 days between study drug in-take in subsequent treatment periods. | 4 |
| Fasted (T2 600 mg+T3 600 mg+T3 50 mg+T2 50 mg)+Fed (T3 600 mg) TAK-831 T2 600 mg, tablet, orally, once, under fasted condition on Day 1 of Treatment Period 1, followed by TAK-831 T3 600 mg, tablet, orally, once, under fasted condition on Day 1 of Treatment Period 2, followed by TAK-831 T3 50 mg, tablet, orally, once, under fasted condition on Day 1 of Treatment Period 3, followed by TAK-831 T2 50 mg, tablet, orally, once, under fasted condition on Day 1 of Treatment Period 4, further followed by TAK-831 T3 600 mg, tablet, orally, once, under fed condition on Day 1 of Treatment Period 5. There was a washout period of at least 7 days between study drug in-take in subsequent treatment periods. | 4 |
| Fasted (T3 600 mg+T2 50 mg+T2 600 mg+T3 50 mg)+Fed (T3 600 mg) TAK-831 T3 600 mg, tablet, orally, once, under fasted condition on Day 1 of Treatment Period 1, followed by TAK-831 T2 50 mg, tablet, orally, once, under fasted condition on Day 1 of Treatment Period 2, followed by TAK-831 T2 600 mg, tablet, orally, once, under fasted condition on Day 1 of Treatment Period 3, followed by TAK-831 T3 50 mg, tablet, orally, once, under fasted condition on Day 1 of Treatment Period 4, further followed by TAK-831 T3 600 mg, tablet, orally, once, under fed condition on Day 1 of Treatment Period 5. There was a washout period of at least 7 days between study drug in-take in subsequent treatment periods. | 4 |
| Total | 16 |
Baseline characteristics
| Characteristic | Fasted (T2 50 mg+T3 50 mg+T3 600 mg+T2 600 mg)+Fed (T3 600 mg) | Fasted (T2 600 mg+T3 600 mg+T3 50 mg+T2 50 mg)+Fed (T3 600 mg) | Total | Fasted (T3 50 mg+T2 600 mg+T2 50 mg+T3 600 mg)+Fed (T3 600 mg) | Fasted (T3 600 mg+T2 50 mg+T2 600 mg+T3 50 mg)+Fed (T3 600 mg) |
|---|---|---|---|---|---|
| Age, Continuous | 40.3 years STANDARD_DEVIATION 10.94 | 31.8 years STANDARD_DEVIATION 9.22 | 37.8 years STANDARD_DEVIATION 11.6 | 49.0 years STANDARD_DEVIATION 8.49 | 30.0 years STANDARD_DEVIATION 9.56 |
| Body mass index (BMI) | 26.060 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 1.6219 | 24.250 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 3.3966 | 25.255 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 2.8796 | 24.090 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 4.1222 | 26.620 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 1.9483 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 4 Participants | 4 Participants | 16 Participants | 4 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Height | 175.3 centimeter (cm) STANDARD_DEVIATION 5.74 | 169.5 centimeter (cm) STANDARD_DEVIATION 13.48 | 170.6 centimeter (cm) STANDARD_DEVIATION 7.79 | 168.3 centimeter (cm) STANDARD_DEVIATION 6.65 | 169.3 centimeter (cm) STANDARD_DEVIATION 2.06 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 3 Participants | 4 Participants | 15 Participants | 4 Participants | 4 Participants |
| Region of Enrollment United States | 4 Participants | 4 Participants | 16 Participants | 4 Participants | 4 Participants |
| Sex: Female, Male Female | 1 Participants | 3 Participants | 10 Participants | 4 Participants | 2 Participants |
| Sex: Female, Male Male | 3 Participants | 1 Participants | 6 Participants | 0 Participants | 2 Participants |
| Weight | 80.48 kilogram (Kg) STANDARD_DEVIATION 9.694 | 70.63 kilogram (Kg) STANDARD_DEVIATION 19.643 | 73.68 kilogram (Kg) STANDARD_DEVIATION 11.66 | 67.55 kilogram (Kg) STANDARD_DEVIATION 6.815 | 76.07 kilogram (Kg) STANDARD_DEVIATION 4.666 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 16 | 0 / 16 | 0 / 16 | 0 / 16 | 0 / 16 |
| other Total, other adverse events | 0 / 16 | 2 / 16 | 0 / 16 | 1 / 16 | 0 / 16 |
| serious Total, serious adverse events | 0 / 16 | 0 / 16 | 0 / 16 | 0 / 16 | 0 / 16 |
Outcome results
Primary
AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-831
Time frame: Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose
Population: The PK analysis set included all participants from the safety set who had at least 1 measurable postdose TAK-831 plasma concentration. The PK analysis population where data at specified time points were available.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| TAK-831 T2 50 mg Fasted | AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-831 | 761.8 ng*hr/mL | Geometric Coefficient of Variation 29.3 |
| TAK-831 T3 50 mg Fasted | AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-831 | 688.6 ng*hr/mL | Geometric Coefficient of Variation 31 |
| TAK-831 T2 600 mg Fasted | AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-831 | 4665 ng*hr/mL | Geometric Coefficient of Variation 26 |
| TAK-831 T3 600 mg Fasted | AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-831 | 4558 ng*hr/mL | Geometric Coefficient of Variation 41.8 |
| TAK-831 T3 600 mg Fed | AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-831 | 7934 ng*hr/mL | Geometric Coefficient of Variation 27.3 |
90% CI: [73.92, 96.11]
90% CI: [88.88, 111.63]
90% CI: [149.07, 200.09]
Primary
AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-831
Time frame: Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose
Population: The pharmacokinetic (PK) analysis set included all participants from the safety set who had at least 1 measurable postdose TAK-831 plasma concentration.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| TAK-831 T2 50 mg Fasted | AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-831 | 714.8 nanogram*hour per milliliter(ng*hr/mL) | Geometric Coefficient of Variation 28.7 |
| TAK-831 T3 50 mg Fasted | AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-831 | 597.5 nanogram*hour per milliliter(ng*hr/mL) | Geometric Coefficient of Variation 37 |
| TAK-831 T2 600 mg Fasted | AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-831 | 4563 nanogram*hour per milliliter(ng*hr/mL) | Geometric Coefficient of Variation 24.8 |
| TAK-831 T3 600 mg Fasted | AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-831 | 4665 nanogram*hour per milliliter(ng*hr/mL) | Geometric Coefficient of Variation 41.8 |
| TAK-831 T3 600 mg Fed | AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-831 | 8058 nanogram*hour per milliliter(ng*hr/mL) | Geometric Coefficient of Variation 29 |
90% CI: [74.5, 93.8]
90% CI: [91.1, 114.7]
90% CI: [152.55, 195.58]
Primary
Cmax: Maximum Observed Plasma Concentration for TAK-831
Time frame: Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose
Population: The PK analysis set included all participants from the safety set who had at least 1 measurable postdose TAK-831 plasma concentration.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| TAK-831 T2 50 mg Fasted | Cmax: Maximum Observed Plasma Concentration for TAK-831 | 397.5 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 38.8 |
| TAK-831 T3 50 mg Fasted | Cmax: Maximum Observed Plasma Concentration for TAK-831 | 314.6 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 40 |
| TAK-831 T2 600 mg Fasted | Cmax: Maximum Observed Plasma Concentration for TAK-831 | 1384 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 28.9 |
| TAK-831 T3 600 mg Fasted | Cmax: Maximum Observed Plasma Concentration for TAK-831 | 1381 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 24.6 |
| TAK-831 T3 600 mg Fed | Cmax: Maximum Observed Plasma Concentration for TAK-831 | 2394 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 37.1 |
90% CI: [67.36, 92.99]
90% CI: [84.94, 117.27]
90% CI: [150.05, 200.16]
Secondary
Percentage of Participants Who Experience at Least One Treatment Emergent Adverse Event (TEAE)
Time frame: Day 1 post dose up to 14 days after the last dose of study drug (Up to Day 47)
Population: The safety analysis set included all participants who received at least one dose of the study drug(s).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TAK-831 T2 50 mg Fasted | Percentage of Participants Who Experience at Least One Treatment Emergent Adverse Event (TEAE) | 0 percentage of participants |
| TAK-831 T3 50 mg Fasted | Percentage of Participants Who Experience at Least One Treatment Emergent Adverse Event (TEAE) | 13 percentage of participants |
| TAK-831 T2 600 mg Fasted | Percentage of Participants Who Experience at Least One Treatment Emergent Adverse Event (TEAE) | 0 percentage of participants |
| TAK-831 T3 600 mg Fasted | Percentage of Participants Who Experience at Least One Treatment Emergent Adverse Event (TEAE) | 6 percentage of participants |
| TAK-831 T3 600 mg Fed | Percentage of Participants Who Experience at Least One Treatment Emergent Adverse Event (TEAE) | 0 percentage of participants |