Epilepsy
Conditions
Keywords
Drug therapy
Brief summary
The purpose of this study is to assess the safety, tolerability and pharmacokinetics (PK) of multiple rising doses of TAK-935 in healthy participants.
Detailed description
The drug being tested in this study is called TAK-935. This study will look at the pharmacokinetics, safety and tolerability of TAK-935 in healthy participants. The study will enroll approximately 56 participants. Participants will be randomly assigned (by chance, like flipping a coin) to 1 of the 5 cohorts in Part 1, which will remain undisclosed to the participant and study doctor during the study (unless there is an urgent medical need): * Part 1, Cohort 1: TAK-935 100 mg QD * Part 1, Cohort 2: TAK-935 300 mg QD * Part 1, Cohort 3: TAK-935 300 mg BID * Part 1, Cohort 4: TAK-935 600 mg QD * Part 1, Cohort 5: TAK-935 400 mg QD Participants will be asked to take the oral solution once or twice a day at the same time for 14 days. An optional Part 2 may be conducted for collecting data to assess the engagement by TAK-935 of the central molecular target cholesterol 24S-hydroxylase (CH24H) by measuring the changes of levels of the metabolite 24S-hydroxycholesterol (24HC). In Part 2, participants will be assigned to up to 2 treatment groups at doses based on the data from other ongoing TAK-935 trials, combined with the safety and tolerability data from Cohorts 1-4 of Part 1. This single center trial will be conducted in the United States. The overall time to participate in this study will be approximately 30 days. Participants will be admitted in the clinic for the first 14 days, and will be contacted by telephone on Day 28 for a follow-up assessment.
Interventions
DRUGTAK-935
TAK-935 oral solution
DRUGPlacebo
TAK-935 placebo-matching oral solution
Sponsors
Takeda
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
All Cohorts 1. Is capable of understanding and complying with protocol requirements. 2. Signs and dates a written, informed consent form and any required privacy authorization prior to the initiation of any study procedures including requesting that a participant fast for any laboratory evaluations. 3. Is a healthy male or female aged 18 to 55 years inclusive, at the time of informed consent and first study medication dose. 4. Weighs at least 45 kilogram (kg) and has a body mass index (BMI) from 18.0 to 30.0 kilogram per square meter (kg/m\^2), inclusive at Screening and Day -1. 5. Male participant who is non-sterilized 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 30 days after last dose. 6. Female participant of childbearing potential who is sexually active with a non-sterilized male partner agrees to use routinely adequate contraception from signing of informed consent and throughout the duration of the study, and for 30 days after the last dose. 7. Can complete the CogState Battery at Screening. Additional Inclusion Criteria for Participants undergoing cerebrospinal fluid (CSF) Sampling (Part 2 only): 8. Agrees to spinal tap procedures for CSF collection.
Exclusion criteria
All Cohorts 1. Has received any investigational compound within 30 days prior to randomization. 2. Has received TAK-935 in a previous clinical study or as a therapeutic agent. 3. Has a significant history of uncontrolled, clinically significant neurologic (including seizure disorders), cardiovascular, pulmonary, hepatic, renal, metabolic, gastrointestinal, urologic, immunologic, endocrine disease or psychiatric disorder or endocrine disease or other abnormality or any significant results from physical examinations, or clinical laboratory results which may impact the ability of the participant to participate or potentially confound the study results. It is the responsibility of the investigator to assess the clinical significance; however, consultation with the Takeda Medical Monitor may be warranted. 4. Has a known hypersensitivity to any component of the formulation of TAK-935. 5. Has a history of drug abuse (defined as any illicit drug use) or a history of alcohol abuse within 1 year prior to the screening visit or is unwilling to agree to abstain from alcohol and drugs throughout the study. One unit is equivalent to a half-pint of beer or a single measure of spirits or 1 small glass of wine. 6. Has taken any excluded medication, supplements, or food products during the time periods listed in the Excluded Medications and Dietary Products table. Additional
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Percentage of Participants Who Experience at Least One Treatment-emergent Adverse Event (TEAE) | Day 1 up to Day 28 |
| Percentage of Participants Who Meet the Takeda Markedly Abnormal Criteria for Safety Laboratory Tests at Least Once Post Dose | Baseline up to Day 15 |
| Percentage of Participants Who Meet the Takeda Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post Dose | Baseline up to Day 15 |
| Percentage of Participants Who Meet the Takeda Markedly Abnormal Criteria for Safety 12-lead Electrocardiogram (ECG) Parameters at Least Once Post Dose | Baseline up to Day 15 |
Secondary
| Measure | Time frame |
|---|---|
| Cmax: Maximum Observed Plasma Concentration for TAK-935 | Day 1 and Day 14: Pre-dose and at multiple time points (up to 24 hours for Cohorts 1, 2, 4, and 5; up to 12 hours for Cohort 3) post-dose |
| AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-935 | Day 1 and Day 14: Pre-dose and at multiple time points (up to 24 hours for Cohorts 1, 2, 4, and 5; up to 12 hours for Cohort 3) post-dose |
| AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-935 | Day 1: Pre-dose and at multiple time points (up to 24 hours for Cohorts 1, 2, 4, and 5; up to 12 hours for Cohort 3) post-dose |
| AUCτ: Area Under the Plasma Concentration-time Curve From Time 0 to Over the Dosing Interval for TAK-935 | Day 14: Pre-dose and at multiple time points (up to 24 hours for Cohorts 1, 2, 4, and 5; up to 12 hours for Cohort 3) post-dose |
Countries
United States
Contacts
STUDY_DIRECTORMedical Director
Takeda (Note: This product was divested to Mistrau Bio, Inc. in 2026)
Participant flow
Recruitment details
Participants took part in the study at 1 investigative site in the United States from 02 September 2015 to 19 April 2016.
Pre-assignment details
Healthy participants received TAK-935 or placebo in Cohorts 1-5: 100 milligram(mg) once daily(QD), 300mg QD, 300mg twice daily(BID), 600mg QD, and 400mg QD respectively in Part 1. Study Part 2 (optional) was not conducted after review of initial data of TAK-935-1003(NCT02497235) along with safety and tolerability data from Cohorts 1 to 4 of Part 1.
Participants by arm
| Arm | Count |
|---|---|
| Cohorts 1-5: Placebo TAK-935 placebo-matching solution, orally, QD for up to 14 days in Cohorts 1, 2, and 5; BID for up to 10 days in Cohort 3 and QD for up to 10 days in Cohort 4. | 10 |
| Cohort 1: TAK-935 100 mg QD TAK-935 100 mg, solution, orally, QD for up to 14 days in Cohort 1. | 6 |
| Cohort 2: TAK-935 300 mg QD TAK-935 300 mg, solution, orally, QD for up to 14 days in Cohort 2. | 6 |
| Cohort 3: TAK-935 300 mg BID TAK-935 300 mg, solution, orally, BID for up to 10 days in Cohort 3. | 6 |
| Cohort 5: TAK-935 400 mg QD TAK-935 400 mg, solution, orally, QD for up to 14 days in Cohort 5. | 6 |
| Cohort 4: TAK-935 600 mg QD TAK-935 600 mg, solution, orally, QD for up to 10 days in Cohort 4. | 6 |
| Total | 40 |
Baseline characteristics
| Characteristic | Total | Cohort 4: TAK-935 600 mg QD | Cohort 5: TAK-935 400 mg QD | Cohort 3: TAK-935 300 mg BID | Cohort 2: TAK-935 300 mg QD | Cohort 1: TAK-935 100 mg QD | Cohorts 1-5: Placebo |
|---|---|---|---|---|---|---|---|
| Age, Continuous | 34.5 years STANDARD_DEVIATION 9.6 | 40.3 years STANDARD_DEVIATION 11.55 | 37.7 years STANDARD_DEVIATION 13.08 | 26.7 years STANDARD_DEVIATION 4.5 | 33.7 years STANDARD_DEVIATION 10.71 | 33.8 years STANDARD_DEVIATION 4.62 | 34.8 years STANDARD_DEVIATION 8.51 |
| Alcohol Classification Current drinker | 6 participants | 2 participants | 1 participants | 1 participants | 1 participants | 1 participants | 0 participants |
| Alcohol Classification Ex-drinker | 9 participants | 1 participants | 2 participants | 1 participants | 1 participants | 1 participants | 3 participants |
| Alcohol Classification Never drunk | 25 participants | 3 participants | 3 participants | 4 participants | 4 participants | 4 participants | 7 participants |
| Body Mass Index | 25.56 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 2.666 | 25.31 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 1.491 | 26.67 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 2.971 | 24.16 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 2.629 | 24.66 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 3.476 | 25.76 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 2.386 | 26.30 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 2.756 |
| Ethnicity Hispanic or Latino | 19 participants | 1 participants | 5 participants | 4 participants | 4 participants | 0 participants | 5 participants |
| Ethnicity Not Hispanic or Latino | 21 participants | 5 participants | 1 participants | 2 participants | 2 participants | 6 participants | 5 participants |
| Female Reproductive Status Female of childbearing potential | 8 participants | 0 participants | 1 participants | 1 participants | 3 participants | 1 participants | 2 participants |
| Female Reproductive Status Not applicable (Male participant) | 30 participants | 6 participants | 4 participants | 5 participants | 3 participants | 5 participants | 7 participants |
| Female Reproductive Status Postmenopausal | 2 participants | 0 participants | 1 participants | 0 participants | 0 participants | 0 participants | 1 participants |
| Height | 172.0 centimeter (cm) STANDARD_DEVIATION 8.19 | 175.7 centimeter (cm) STANDARD_DEVIATION 5.43 | 167.5 centimeter (cm) STANDARD_DEVIATION 7.29 | 174.8 centimeter (cm) STANDARD_DEVIATION 8.57 | 165.5 centimeter (cm) STANDARD_DEVIATION 6.16 | 175.5 centimeter (cm) STANDARD_DEVIATION 5.65 | 172.7 centimeter (cm) STANDARD_DEVIATION 10.02 |
| Race Black or African American | 9 participants | 1 participants | 1 participants | 1 participants | 2 participants | 1 participants | 3 participants |
| Race White | 31 participants | 5 participants | 5 participants | 5 participants | 4 participants | 5 participants | 7 participants |
| Region of Enrollment United States | 40 participants | 6 participants | 6 participants | 6 participants | 6 participants | 6 participants | 10 participants |
| Sex: Female, Male Female | 10 Participants | 0 Participants | 2 Participants | 1 Participants | 3 Participants | 1 Participants | 3 Participants |
| Sex: Female, Male Male | 30 Participants | 6 Participants | 4 Participants | 5 Participants | 3 Participants | 5 Participants | 7 Participants |
| Smoking Classification Ex-smoker | 8 participants | 2 participants | 2 participants | 0 participants | 0 participants | 1 participants | 3 participants |
| Smoking Classification Never smoked | 32 participants | 4 participants | 4 participants | 6 participants | 6 participants | 5 participants | 7 participants |
| Weight | 75.85 kilogram (kg) STANDARD_DEVIATION 10.647 | 78.25 kilogram (kg) STANDARD_DEVIATION 7.936 | 75.28 kilogram (kg) STANDARD_DEVIATION 12.367 | 73.55 kilogram (kg) STANDARD_DEVIATION 6.227 | 67.68 kilogram (kg) STANDARD_DEVIATION 10.86 | 79.37 kilogram (kg) STANDARD_DEVIATION 8.596 | 78.90 kilogram (kg) STANDARD_DEVIATION 13.136 |
| Xanthine/Caffeine Consumption No Xanthine/Caffeine consumption | 19 participants | 2 participants | 3 participants | 4 participants | 2 participants | 4 participants | 4 participants |
| Xanthine/Caffeine Consumption Xanthine/Caffeine consumption | 21 participants | 4 participants | 3 participants | 2 participants | 4 participants | 2 participants | 6 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| other Total, other adverse events | 4 / 10 | 0 / 6 | 1 / 6 | 5 / 6 | 5 / 6 | 3 / 6 |
| serious Total, serious adverse events | 0 / 10 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 |
Outcome results
Primary
Percentage of Participants Who Experience at Least One Treatment-emergent Adverse Event (TEAE)
Time frame: Day 1 up to Day 28
Population: The safety analysis set included all participants who were enrolled and received study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohorts 1-5: Placebo | Percentage of Participants Who Experience at Least One Treatment-emergent Adverse Event (TEAE) | 40.0 percentage of participants |
| Cohort 1: TAK-935 100 mg QD | Percentage of Participants Who Experience at Least One Treatment-emergent Adverse Event (TEAE) | 0 percentage of participants |
| Cohort 2: TAK-935 300 mg QD | Percentage of Participants Who Experience at Least One Treatment-emergent Adverse Event (TEAE) | 16.7 percentage of participants |
| Cohort 3: TAK-935 300 mg BID | Percentage of Participants Who Experience at Least One Treatment-emergent Adverse Event (TEAE) | 83.3 percentage of participants |
| Cohort 5: TAK-935 400 mg QD | Percentage of Participants Who Experience at Least One Treatment-emergent Adverse Event (TEAE) | 83.3 percentage of participants |
| Cohort 4: TAK-935 600 mg QD | Percentage of Participants Who Experience at Least One Treatment-emergent Adverse Event (TEAE) | 50.0 percentage of participants |
Primary
Percentage of Participants Who Meet the Takeda Markedly Abnormal Criteria for Safety 12-lead Electrocardiogram (ECG) Parameters at Least Once Post Dose
Time frame: Baseline up to Day 15
Population: The safety analysis set included all participants who were enrolled and received study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohorts 1-5: Placebo | Percentage of Participants Who Meet the Takeda Markedly Abnormal Criteria for Safety 12-lead Electrocardiogram (ECG) Parameters at Least Once Post Dose | 70.0 percentage of participants |
| Cohort 1: TAK-935 100 mg QD | Percentage of Participants Who Meet the Takeda Markedly Abnormal Criteria for Safety 12-lead Electrocardiogram (ECG) Parameters at Least Once Post Dose | 66.7 percentage of participants |
| Cohort 2: TAK-935 300 mg QD | Percentage of Participants Who Meet the Takeda Markedly Abnormal Criteria for Safety 12-lead Electrocardiogram (ECG) Parameters at Least Once Post Dose | 33.3 percentage of participants |
| Cohort 3: TAK-935 300 mg BID | Percentage of Participants Who Meet the Takeda Markedly Abnormal Criteria for Safety 12-lead Electrocardiogram (ECG) Parameters at Least Once Post Dose | 66.7 percentage of participants |
| Cohort 5: TAK-935 400 mg QD | Percentage of Participants Who Meet the Takeda Markedly Abnormal Criteria for Safety 12-lead Electrocardiogram (ECG) Parameters at Least Once Post Dose | 50.0 percentage of participants |
| Cohort 4: TAK-935 600 mg QD | Percentage of Participants Who Meet the Takeda Markedly Abnormal Criteria for Safety 12-lead Electrocardiogram (ECG) Parameters at Least Once Post Dose | 66.7 percentage of participants |
Primary
Percentage of Participants Who Meet the Takeda Markedly Abnormal Criteria for Safety Laboratory Tests at Least Once Post Dose
Time frame: Baseline up to Day 15
Population: The safety analysis set included all participants who were enrolled and received study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohorts 1-5: Placebo | Percentage of Participants Who Meet the Takeda Markedly Abnormal Criteria for Safety Laboratory Tests at Least Once Post Dose | 0 percentage of participants |
| Cohort 1: TAK-935 100 mg QD | Percentage of Participants Who Meet the Takeda Markedly Abnormal Criteria for Safety Laboratory Tests at Least Once Post Dose | 0 percentage of participants |
| Cohort 2: TAK-935 300 mg QD | Percentage of Participants Who Meet the Takeda Markedly Abnormal Criteria for Safety Laboratory Tests at Least Once Post Dose | 0 percentage of participants |
| Cohort 3: TAK-935 300 mg BID | Percentage of Participants Who Meet the Takeda Markedly Abnormal Criteria for Safety Laboratory Tests at Least Once Post Dose | 16.7 percentage of participants |
| Cohort 5: TAK-935 400 mg QD | Percentage of Participants Who Meet the Takeda Markedly Abnormal Criteria for Safety Laboratory Tests at Least Once Post Dose | 0 percentage of participants |
| Cohort 4: TAK-935 600 mg QD | Percentage of Participants Who Meet the Takeda Markedly Abnormal Criteria for Safety Laboratory Tests at Least Once Post Dose | 0 percentage of participants |
Primary
Percentage of Participants Who Meet the Takeda Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post Dose
Time frame: Baseline up to Day 15
Population: The safety analysis set included all participants who were enrolled and received study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohorts 1-5: Placebo | Percentage of Participants Who Meet the Takeda Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post Dose | 70 percentage of participants |
| Cohort 1: TAK-935 100 mg QD | Percentage of Participants Who Meet the Takeda Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post Dose | 33.3 percentage of participants |
| Cohort 2: TAK-935 300 mg QD | Percentage of Participants Who Meet the Takeda Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post Dose | 33.3 percentage of participants |
| Cohort 3: TAK-935 300 mg BID | Percentage of Participants Who Meet the Takeda Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post Dose | 0 percentage of participants |
| Cohort 5: TAK-935 400 mg QD | Percentage of Participants Who Meet the Takeda Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post Dose | 33.3 percentage of participants |
| Cohort 4: TAK-935 600 mg QD | Percentage of Participants Who Meet the Takeda Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post Dose | 33.3 percentage of participants |
Secondary
AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-935
Time frame: Day 1: Pre-dose and at multiple time points (up to 24 hours for Cohorts 1, 2, 4, and 5; up to 12 hours for Cohort 3) post-dose
Population: The PK set where Day 1 assessment for AUC∞ was available. The PK set included all participants in the safety set who had at least 1 measurable plasma or urine concentration.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cohorts 1-5: Placebo | AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-935 | 427.418 ng*hr/mL | Geometric Coefficient of Variation 36.7 |
| Cohort 1: TAK-935 100 mg QD | AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-935 | 1811.936 ng*hr/mL | Geometric Coefficient of Variation 55.3 |
| Cohort 2: TAK-935 300 mg QD | AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-935 | 1397.108 ng*hr/mL | Geometric Coefficient of Variation 48 |
| Cohort 3: TAK-935 300 mg BID | AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-935 | 2310.461 ng*hr/mL | Geometric Coefficient of Variation 48.1 |
| Cohort 5: TAK-935 400 mg QD | AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-935 | 3606.449 ng*hr/mL | Geometric Coefficient of Variation 59.4 |
Comparison: Day 1: For groups with QD dosing, dose proportionality for TAK-935 plasma exposure on Day 1 was assessed using the power model. For Day 1, the criteria for dose proportionality was the 90% CI for the slope within (0.875, 1.125) for the dose range of 100 mg to 600 mg.p-value: 0.28890% CI: [0.89, 1.489]Power model
Secondary
AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-935
Time frame: Day 1 and Day 14: Pre-dose and at multiple time points (up to 24 hours for Cohorts 1, 2, 4, and 5; up to 12 hours for Cohort 3) post-dose
Population: The PK set included all participants in the safety set who had at least 1 measurable plasma or urine concentration.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohorts 1-5: Placebo | AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-935 | Day 1 | 423.284 nanogram*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 29.8 |
| Cohorts 1-5: Placebo | AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-935 | Day 14 | 435.232 nanogram*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 29.5 |
| Cohort 1: TAK-935 100 mg QD | AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-935 | Day 1 | 1794.084 nanogram*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 55.7 |
| Cohort 1: TAK-935 100 mg QD | AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-935 | Day 14 | 2494.972 nanogram*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 40 |
| Cohort 2: TAK-935 300 mg QD | AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-935 | Day 1 | 1250.256 nanogram*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 38.5 |
| Cohort 2: TAK-935 300 mg QD | AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-935 | Day 14 | NA nanogram*hour per milliliter (ng*hr/mL) | — |
| Cohort 3: TAK-935 300 mg BID | AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-935 | Day 14 | 2601.519 nanogram*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 40.4 |
| Cohort 3: TAK-935 300 mg BID | AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-935 | Day 1 | 2281.664 nanogram*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 48.8 |
| Cohort 5: TAK-935 400 mg QD | AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-935 | Day 1 | 3563.187 nanogram*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 59.7 |
| Cohort 5: TAK-935 400 mg QD | AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-935 | Day 14 | NA nanogram*hour per milliliter (ng*hr/mL) | — |
Comparison: Day 1: For groups with QD dosing, dose proportionality for TAK-935 plasma exposure on Day 1 was assessed using the power model. For Day 1, the criteria for dose proportionality was the 90% CI for the slope within (0.875, 1.125) for the dose range of 100 mg to 600 mg.p-value: 0.19190% CI: [0.946, 1.45]Power model
Comparison: Day 14: For groups with QD dosing, dose proportionality for TAK-935 plasma exposure on Day 14 was assessed using the power model. For Day 14, the criteria for dose proportionality was the 90% CI for the slope within (0.839, 1.161) for the dose range of 100 mg to 400 mg.p-value: 0.03690% CI: [1.089, 1.657]Power model
Secondary
AUCτ: Area Under the Plasma Concentration-time Curve From Time 0 to Over the Dosing Interval for TAK-935
Time frame: Day 14: Pre-dose and at multiple time points (up to 24 hours for Cohorts 1, 2, 4, and 5; up to 12 hours for Cohort 3) post-dose
Population: The PK set included all participants in the safety set who had at least 1 measurable plasma or urine concentration. No data was reported for Cohorts 3 and 4 since dosing was discontinued after Day 10.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cohorts 1-5: Placebo | AUCτ: Area Under the Plasma Concentration-time Curve From Time 0 to Over the Dosing Interval for TAK-935 | 442.606 ng*hr/mL | Geometric Coefficient of Variation 28.4 |
| Cohort 1: TAK-935 100 mg QD | AUCτ: Area Under the Plasma Concentration-time Curve From Time 0 to Over the Dosing Interval for TAK-935 | 2496.596 ng*hr/mL | Geometric Coefficient of Variation 40 |
| Cohort 3: TAK-935 300 mg BID | AUCτ: Area Under the Plasma Concentration-time Curve From Time 0 to Over the Dosing Interval for TAK-935 | 2605.230 ng*hr/mL | Geometric Coefficient of Variation 40.3 |
Comparison: Day 14: For groups with QD dosing, dose proportionality for TAK-935 plasma exposure on Day 14 was assessed using the power model. For Day 14, the criteria for dose proportionality was the 90% CI for the slope within (0.839, 1.161) for the dose range of 100 mg to 400 mg.p-value: 0.03990% CI: [1.08, 1.642]Power model
Secondary
Cmax: Maximum Observed Plasma Concentration for TAK-935
Time frame: Day 1 and Day 14: Pre-dose and at multiple time points (up to 24 hours for Cohorts 1, 2, 4, and 5; up to 12 hours for Cohort 3) post-dose
Population: The pharmacokinetic (PK) set included all participants in the safety set who had at least 1 measurable plasma or urine concentration.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohorts 1-5: Placebo | Cmax: Maximum Observed Plasma Concentration for TAK-935 | Day 1 | 418.536 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 50 |
| Cohorts 1-5: Placebo | Cmax: Maximum Observed Plasma Concentration for TAK-935 | Day 14 | 469.137 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 25.3 |
| Cohort 1: TAK-935 100 mg QD | Cmax: Maximum Observed Plasma Concentration for TAK-935 | Day 1 | 1729.173 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 61.7 |
| Cohort 1: TAK-935 100 mg QD | Cmax: Maximum Observed Plasma Concentration for TAK-935 | Day 14 | 2865.655 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 41.1 |
| Cohort 2: TAK-935 300 mg QD | Cmax: Maximum Observed Plasma Concentration for TAK-935 | Day 1 | 1269.337 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 32.5 |
| Cohort 2: TAK-935 300 mg QD | Cmax: Maximum Observed Plasma Concentration for TAK-935 | Day 14 | NA nanogram per milliliter (ng/mL) | — |
| Cohort 3: TAK-935 300 mg BID | Cmax: Maximum Observed Plasma Concentration for TAK-935 | Day 14 | 2708.655 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 40.3 |
| Cohort 3: TAK-935 300 mg BID | Cmax: Maximum Observed Plasma Concentration for TAK-935 | Day 1 | 2374.498 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 50.6 |
| Cohort 5: TAK-935 400 mg QD | Cmax: Maximum Observed Plasma Concentration for TAK-935 | Day 1 | 2448.500 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 70.2 |
| Cohort 5: TAK-935 400 mg QD | Cmax: Maximum Observed Plasma Concentration for TAK-935 | Day 14 | NA nanogram per milliliter (ng/mL) | — |
Comparison: Day 1: For groups with QD dosing, dose proportionality for TAK-935 plasma exposure on Day 1 was assessed using the power model. For Day 1, the criteria for dose proportionality was the 90 percent (%) confidence interval (CI) for the slope within (0.875, 1.125) for the dose range of 100 mg to 600 mg.p-value: 0.75790% CI: [0.741, 1.374]Power model
Comparison: Day 14: For groups with QD dosing, dose proportionality for TAK-935 plasma exposure on Day 14 was assessed using the power model. For Day 14, the criteria for dose proportionality was the 90% CI for the slope within (0.839, 1.161) for the dose range of 100 mg to 400 mg.p-value: 0.04290% CI: [1.078, 1.664]Power model