Attention-Deficit/Hyperactivity Disorder
Conditions
Keywords
Drug therapy
Brief summary
The purpose of this study is to characterize the safety and tolerability of TAK-137 when administered as multiple oral doses in adults with attention-deficit/hyperactivity disorder (ADHD).
Detailed description
The drug being tested in this study is called TAK-137. TAK-137 is being tested to find a safe and well-tolerated dose and to assess how TAK-137 is metabolized in people with attention-deficit/ hyperactivity disorder (ADHD). This study will look at side effects and lab results in people who take TAK-137. This study is designed as a randomized, sequential-cohort, multiple rising dose study. Therefore, the TAK-137 2 mg Cohort will not start until the TAK-137 0.5 mg Cohort has completed, etc. This trial will be conducted in the United States. The overall time to participate in this study is up to 42 days. Participants will make at least 2 visits to the clinic, including one 9-day period of confinement to the clinic. All participants will be contacted by telephone 7 days after the last dose of study drug for a follow-up assessment. A decision was made to terminate this study so that emerging data from preclinical studies could be further assessed.
Interventions
DRUGTAK-137
TAK-137 tablets
DRUGTAK-137 Placebo
TAK-137 placebo-matching tablets
Sponsors
Takeda
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
No
Inclusion criteria
1. Is a male or female adult who is 18 to 55 years of age, inclusive. 2. Weighs at least 45 kg and has a body mass index (BMI) between 18 and 30.0 kg/m\^2, inclusive at Screening. 3. Has a documented diagnosis of attention-deficit/hyperactivity disorder (ADHD) for a minimum of 1 year. 4. Is willing to discontinue all medications to treat adult ADHD (eg, stimulants, antidepressants) and all other medications and dietary products as specified in the protocol, from Day -7 until Follow-up phone call (Day 14).
Exclusion criteria
1. Has received any investigational compound within 30 days prior to the first dose of study medication. 2. Has uncontrolled, clinically significant neurologic (including mildly abnormal or significantly abnormal EEG at screening), cardiovascular, pulmonary, hepatic, renal, metabolic, gastrointestinal, urologic, immunologic, endocrine disease, or psychiatric disorder (other than ADHD), or other abnormality, which may impact the ability of the participant to participate or potentially confound the study results. 3. Has previously had a seizure or convulsion (lifetime), including absence seizure and febrile convulsion. 4. Has a positive urine drug result for drugs of abuse other than amphetamines or other medications to treat ADHD or positive result for alcohol at Screening or Check-in (Day -1). 5. Has taken any excluded medication, supplements, or food products listed in the Excluded Medications and Dietary Products. 6. Is pregnant or lactating or intending to become pregnant before, during, or within 12 weeks after participating in this study; or intending to donate ova during such time period. 7. Has used nicotine-containing products (including but not limited to cigarettes, pipes, cigars, chewing tobacco, nicotine patch or nicotine gum) within 28 days prior to Check-in (Day -1).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Meet the Takeda Markedly Abnormal Criteria for Safety Electrocardiogram (ECG) Parameters at Least Once Post Dose | Day 1 up to Day 8 | — |
| Percentage of Participants Who Meet the Takeda Markedly Abnormal Criteria for Safety Laboratory Tests at Least Once Post Dose | Day 1 up to Day 8 | — |
| Percentage of Participants Who Meet the Takeda Markedly Abnormal Criteria for Pulse Measurements at Least Once Post Dose | Day 1 up to Day 8 | — |
| Percentage of Participants Who Meet the Takeda Markedly Abnormal Criteria for Blood Pressure Measurements at Least Once Post Dose | Day 1 up to Day 8 | — |
| Percentage of Participants Who Meet the Takeda Markedly Abnormal Criteria for Heart Rate Measurements at Least Once Post Dose | Day 1 up to Day 8 | — |
| Percentage of Participants Who Experience at Least One Treatment Emergent Adverse Event (TEAE) | Day 1 up to Day 14 | 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. An AE can therefore be any unfavorable and unintended sign (example, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. A treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cmax, ss: Maximum Observed Plasma Concentration at Steady State for TAK-137 | Day 7 pre-dose and at multiple timepoints (up to 24 hours) post-dose | Maximum observed steady-state plasma concentration during a dosing interval. |
| Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-137 | Days 1 and 7 pre-dose and at multiple timepoints (up to 24 hours) post-dose | Tmax: Time to reach the maximum plasma concentration (Cmax), equal to time (hours) to Cmax. |
| AUC(0-tau): Area Under the Plasma Concentration-time Curve From Time 0 to Time Tau Over the Dosing Interval for TAK-137 | Days 1 and 7 pre-dose and at multiple timepoints (up to 24 hours) post-dose | Area under the plasma concentration-time curve during a dosing interval, where tau is the length of the dosing interval. |
| Cmax: Maximum Observed Plasma Concentration for TAK-137 | Day 1 pre-dose and at multiple timepoints (up to 24 hours) post-dose | Maximum observed plasma concentration (Cmax) is the peak plasma concentration of a drug after administration, obtained directly from the plasma concentration-time curve. |
Countries
United States
Participant flow
Recruitment details
Participants took part in the study at 1 investigative site in the United States from 23 May 2014 to 03 November 2014.
Pre-assignment details
Participants with a historical diagnosis of attention-deficit/hyperactivity disorder (ADHD) were enrolled in one of the five cohorts to receive TAK-137 (0.5 milligram \[mg\], 2 mg, 5 mg, 10 mg, or matching placebo) once daily for up to 7 days.
Participants by arm
| Arm | Count |
|---|---|
| Cohorts 1-4: Placebo TAK-137 placebo-matching tablets, orally, once on Days 1-7 under fasting conditions. | 10 |
| Cohort 1: TAK-137 0.5 mg TAK-137 0.5 mg, tablets, orally once on Days 1-7 under fasting condition. | 8 |
| Cohort 2: TAK-137 2 mg TAK-137 2 mg, tablets, orally once on Days 1-7 under fasting condition. | 10 |
| Cohort 3: TAK-137 5 mg TAK-137 5 mg, tablets, orally once on Days 1-7 under fasting condition. | 9 |
| Cohort 4: TAK-137 10 mg TAK-137 10 mg, tablets, orally once on Days 1-7 under fasting condition. | 10 |
| Total | 47 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Physician Decision | 0 | 0 | 0 | 1 | 0 |
| Overall Study | Study termination | 1 | 0 | 0 | 0 | 2 |
| Overall Study | Withdrawal by Subject | 2 | 0 | 2 | 2 | 2 |
Baseline characteristics
| Characteristic | Cohorts 1-4: Placebo | Cohort 1: TAK-137 0.5 mg | Cohort 2: TAK-137 2 mg | Total | Cohort 3: TAK-137 5 mg | Cohort 4: TAK-137 10 mg |
|---|---|---|---|---|---|---|
| ADHD Category Combined | 9 participants | 8 participants | 8 participants | 43 participants | 9 participants | 9 participants |
| ADHD Category Inattentive | 1 participants | 0 participants | 2 participants | 4 participants | 0 participants | 1 participants |
| Age, Continuous | 28.1 years STANDARD_DEVIATION 10.59 | 33.0 years STANDARD_DEVIATION 9.65 | 28.6 years STANDARD_DEVIATION 8.75 | 30.6 years STANDARD_DEVIATION 10.1 | 32.6 years STANDARD_DEVIATION 10.73 | 31.6 years STANDARD_DEVIATION 11.68 |
| Alcohol consumption Current drinker | 4 participants | 3 participants | 5 participants | 17 participants | 4 participants | 1 participants |
| Alcohol consumption Ex-drinker | 1 participants | 1 participants | 0 participants | 3 participants | 1 participants | 0 participants |
| Alcohol consumption Never drank | 5 participants | 4 participants | 5 participants | 27 participants | 4 participants | 9 participants |
| Body Mass Index | 26.25 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 3.182 | 25.46 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 3.408 | 25.36 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 3.942 | 25.64 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 3.303 | 26.02 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 2.204 | 25.09 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 3.969 |
| Caffeine Consumption Had caffeine consumption | 7 participants | 5 participants | 6 participants | 29 participants | 7 participants | 4 participants |
| Caffeine Consumption Had no caffeine consumption | 3 participants | 3 participants | 4 participants | 18 participants | 2 participants | 6 participants |
| Female Reproductive Status Female of childbearing potential | 4 participants | 0 participants | 1 participants | 9 participants | 1 participants | 3 participants |
| Female Reproductive Status Not applicable | 5 participants | 7 participants | 9 participants | 35 participants | 7 participants | 7 participants |
| Female Reproductive Status Surgically sterile | 1 participants | 1 participants | 0 participants | 3 participants | 1 participants | 0 participants |
| Height | 171.8 centimeter (cm) STANDARD_DEVIATION 7.96 | 172.4 centimeter (cm) STANDARD_DEVIATION 9.07 | 171.7 centimeter (cm) STANDARD_DEVIATION 7.09 | 172.6 centimeter (cm) STANDARD_DEVIATION 7.13 | 174.8 centimeter (cm) STANDARD_DEVIATION 7.36 | 172.4 centimeter (cm) STANDARD_DEVIATION 5.23 |
| Race/Ethnicity, Customized Black or African American | 5 participants | 2 participants | 6 participants | 24 participants | 4 participants | 7 participants |
| Race/Ethnicity, Customized Hispanic or Latino | 2 participants | 0 participants | 2 participants | 8 participants | 1 participants | 3 participants |
| Race/Ethnicity, Customized Multiracial | 1 participants | 2 participants | 0 participants | 3 participants | 0 participants | 0 participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 participants | 1 participants | 0 participants | 1 participants | 0 participants | 0 participants |
| Race/Ethnicity, Customized Non-Hispanic or Latino | 8 participants | 8 participants | 8 participants | 39 participants | 8 participants | 7 participants |
| Race/Ethnicity, Customized White | 4 participants | 3 participants | 4 participants | 19 participants | 5 participants | 3 participants |
| Sex: Female, Male Female | 5 Participants | 1 Participants | 1 Participants | 12 Participants | 2 Participants | 3 Participants |
| Sex: Female, Male Male | 5 Participants | 7 Participants | 9 Participants | 35 Participants | 7 Participants | 7 Participants |
| Smoking Status Ex-smoker | 2 participants | 1 participants | 2 participants | 7 participants | 1 participants | 1 participants |
| Smoking Status Never smoked | 8 participants | 7 participants | 8 participants | 40 participants | 8 participants | 9 participants |
| Weight | 77.42 kilogram (kg) STANDARD_DEVIATION 10.211 | 76.01 kilogram (kg) STANDARD_DEVIATION 14.537 | 75.11 kilogram (kg) STANDARD_DEVIATION 14.376 | 76.54 kilogram (kg) STANDARD_DEVIATION 12.777 | 79.61 kilogram (kg) STANDARD_DEVIATION 9.205 | 74.73 kilogram (kg) STANDARD_DEVIATION 13.815 |
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 | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 5 / 10 | 5 / 8 | 0 / 10 | 6 / 9 | 2 / 10 |
| serious Total, serious adverse events | 0 / 10 | 0 / 8 | 0 / 10 | 0 / 9 | 0 / 10 |
Outcome results
Primary
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. An AE can therefore be any unfavorable and unintended sign (example, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. A treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug.
Time frame: Day 1 up to Day 14
Population: Safety analysis set was defined as all participants who received at least one dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohorts 1-4: Placebo | Percentage of Participants Who Experience at Least One Treatment Emergent Adverse Event (TEAE) | 50.0 percentage of participants |
| Cohort 1: TAK-137 0.5 mg | Percentage of Participants Who Experience at Least One Treatment Emergent Adverse Event (TEAE) | 62.5 percentage of participants |
| Cohort 2: TAK-137 2 mg | Percentage of Participants Who Experience at Least One Treatment Emergent Adverse Event (TEAE) | 0 percentage of participants |
| Cohort 3: TAK-137 5 mg | Percentage of Participants Who Experience at Least One Treatment Emergent Adverse Event (TEAE) | 66.7 percentage of participants |
| Cohort 4: TAK-137 10 mg | Percentage of Participants Who Experience at Least One Treatment Emergent Adverse Event (TEAE) | 20.0 percentage of participants |
Primary
Percentage of Participants Who Meet the Takeda Markedly Abnormal Criteria for Blood Pressure Measurements at Least Once Post Dose
Time frame: Day 1 up to Day 8
Population: Safety analysis set was defined as all participants who received at least one dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohorts 1-4: Placebo | Percentage of Participants Who Meet the Takeda Markedly Abnormal Criteria for Blood Pressure Measurements at Least Once Post Dose | SBP: Supine, After 5 Minutes: < 85 mmHg | 10 percentage of participants |
| Cohorts 1-4: Placebo | Percentage of Participants Who Meet the Takeda Markedly Abnormal Criteria for Blood Pressure Measurements at Least Once Post Dose | DBP: Standing, After 3 Minutes: >110 mmHg | 0 percentage of participants |
| Cohorts 1-4: Placebo | Percentage of Participants Who Meet the Takeda Markedly Abnormal Criteria for Blood Pressure Measurements at Least Once Post Dose | DBP: Standing, After 3 Minutes: <50 mmHg | 30 percentage of participants |
| Cohorts 1-4: Placebo | Percentage of Participants Who Meet the Takeda Markedly Abnormal Criteria for Blood Pressure Measurements at Least Once Post Dose | DBP: Supine, After 5 Minutes: <50 mmHg | 30 percentage of participants |
| Cohorts 1-4: Placebo | Percentage of Participants Who Meet the Takeda Markedly Abnormal Criteria for Blood Pressure Measurements at Least Once Post Dose | SBP: Standing, After 3 Minutes: <85 mmHg | 0 percentage of participants |
| Cohorts 1-4: Placebo | Percentage of Participants Who Meet the Takeda Markedly Abnormal Criteria for Blood Pressure Measurements at Least Once Post Dose | DBP: Standing, After 1 Minute: <50 mmHg | 30 percentage of participants |
| Cohorts 1-4: Placebo | Percentage of Participants Who Meet the Takeda Markedly Abnormal Criteria for Blood Pressure Measurements at Least Once Post Dose | DBP: Standing, After 1 Minute: >110 mmHg | 0 percentage of participants |
| Cohort 1: TAK-137 0.5 mg | Percentage of Participants Who Meet the Takeda Markedly Abnormal Criteria for Blood Pressure Measurements at Least Once Post Dose | DBP: Standing, After 1 Minute: >110 mmHg | 0 percentage of participants |
| Cohort 1: TAK-137 0.5 mg | Percentage of Participants Who Meet the Takeda Markedly Abnormal Criteria for Blood Pressure Measurements at Least Once Post Dose | DBP: Standing, After 1 Minute: <50 mmHg | 0 percentage of participants |
| Cohort 1: TAK-137 0.5 mg | Percentage of Participants Who Meet the Takeda Markedly Abnormal Criteria for Blood Pressure Measurements at Least Once Post Dose | SBP: Standing, After 3 Minutes: <85 mmHg | 0 percentage of participants |
| Cohort 1: TAK-137 0.5 mg | Percentage of Participants Who Meet the Takeda Markedly Abnormal Criteria for Blood Pressure Measurements at Least Once Post Dose | SBP: Supine, After 5 Minutes: < 85 mmHg | 0 percentage of participants |
| Cohort 1: TAK-137 0.5 mg | Percentage of Participants Who Meet the Takeda Markedly Abnormal Criteria for Blood Pressure Measurements at Least Once Post Dose | DBP: Standing, After 3 Minutes: <50 mmHg | 25 percentage of participants |
| Cohort 1: TAK-137 0.5 mg | Percentage of Participants Who Meet the Takeda Markedly Abnormal Criteria for Blood Pressure Measurements at Least Once Post Dose | DBP: Supine, After 5 Minutes: <50 mmHg | 25 percentage of participants |
| Cohort 1: TAK-137 0.5 mg | Percentage of Participants Who Meet the Takeda Markedly Abnormal Criteria for Blood Pressure Measurements at Least Once Post Dose | DBP: Standing, After 3 Minutes: >110 mmHg | 0 percentage of participants |
| Cohort 2: TAK-137 2 mg | Percentage of Participants Who Meet the Takeda Markedly Abnormal Criteria for Blood Pressure Measurements at Least Once Post Dose | DBP: Standing, After 1 Minute: <50 mmHg | 10 percentage of participants |
| Cohort 2: TAK-137 2 mg | Percentage of Participants Who Meet the Takeda Markedly Abnormal Criteria for Blood Pressure Measurements at Least Once Post Dose | SBP: Supine, After 5 Minutes: < 85 mmHg | 0 percentage of participants |
| Cohort 2: TAK-137 2 mg | Percentage of Participants Who Meet the Takeda Markedly Abnormal Criteria for Blood Pressure Measurements at Least Once Post Dose | SBP: Standing, After 3 Minutes: <85 mmHg | 0 percentage of participants |
| Cohort 2: TAK-137 2 mg | Percentage of Participants Who Meet the Takeda Markedly Abnormal Criteria for Blood Pressure Measurements at Least Once Post Dose | DBP: Supine, After 5 Minutes: <50 mmHg | 10 percentage of participants |
| Cohort 2: TAK-137 2 mg | Percentage of Participants Who Meet the Takeda Markedly Abnormal Criteria for Blood Pressure Measurements at Least Once Post Dose | DBP: Standing, After 1 Minute: >110 mmHg | 0 percentage of participants |
| Cohort 2: TAK-137 2 mg | Percentage of Participants Who Meet the Takeda Markedly Abnormal Criteria for Blood Pressure Measurements at Least Once Post Dose | DBP: Standing, After 3 Minutes: <50 mmHg | 30 percentage of participants |
| Cohort 2: TAK-137 2 mg | Percentage of Participants Who Meet the Takeda Markedly Abnormal Criteria for Blood Pressure Measurements at Least Once Post Dose | DBP: Standing, After 3 Minutes: >110 mmHg | 0 percentage of participants |
| Cohort 3: TAK-137 5 mg | Percentage of Participants Who Meet the Takeda Markedly Abnormal Criteria for Blood Pressure Measurements at Least Once Post Dose | DBP: Supine, After 5 Minutes: <50 mmHg | 44.4 percentage of participants |
| Cohort 3: TAK-137 5 mg | Percentage of Participants Who Meet the Takeda Markedly Abnormal Criteria for Blood Pressure Measurements at Least Once Post Dose | DBP: Standing, After 1 Minute: >110 mmHg | 0 percentage of participants |
| Cohort 3: TAK-137 5 mg | Percentage of Participants Who Meet the Takeda Markedly Abnormal Criteria for Blood Pressure Measurements at Least Once Post Dose | SBP: Standing, After 3 Minutes: <85 mmHg | 0 percentage of participants |
| Cohort 3: TAK-137 5 mg | Percentage of Participants Who Meet the Takeda Markedly Abnormal Criteria for Blood Pressure Measurements at Least Once Post Dose | DBP: Standing, After 3 Minutes: >110 mmHg | 11.1 percentage of participants |
| Cohort 3: TAK-137 5 mg | Percentage of Participants Who Meet the Takeda Markedly Abnormal Criteria for Blood Pressure Measurements at Least Once Post Dose | DBP: Standing, After 3 Minutes: <50 mmHg | 44.4 percentage of participants |
| Cohort 3: TAK-137 5 mg | Percentage of Participants Who Meet the Takeda Markedly Abnormal Criteria for Blood Pressure Measurements at Least Once Post Dose | SBP: Supine, After 5 Minutes: < 85 mmHg | 11.1 percentage of participants |
| Cohort 3: TAK-137 5 mg | Percentage of Participants Who Meet the Takeda Markedly Abnormal Criteria for Blood Pressure Measurements at Least Once Post Dose | DBP: Standing, After 1 Minute: <50 mmHg | 22.2 percentage of participants |
| Cohort 4: TAK-137 10 mg | Percentage of Participants Who Meet the Takeda Markedly Abnormal Criteria for Blood Pressure Measurements at Least Once Post Dose | DBP: Supine, After 5 Minutes: <50 mmHg | 0 percentage of participants |
| Cohort 4: TAK-137 10 mg | Percentage of Participants Who Meet the Takeda Markedly Abnormal Criteria for Blood Pressure Measurements at Least Once Post Dose | DBP: Standing, After 3 Minutes: >110 mmHg | 10 percentage of participants |
| Cohort 4: TAK-137 10 mg | Percentage of Participants Who Meet the Takeda Markedly Abnormal Criteria for Blood Pressure Measurements at Least Once Post Dose | DBP: Standing, After 3 Minutes: <50 mmHg | 20 percentage of participants |
| Cohort 4: TAK-137 10 mg | Percentage of Participants Who Meet the Takeda Markedly Abnormal Criteria for Blood Pressure Measurements at Least Once Post Dose | DBP: Standing, After 1 Minute: >110 mmHg | 10 percentage of participants |
| Cohort 4: TAK-137 10 mg | Percentage of Participants Who Meet the Takeda Markedly Abnormal Criteria for Blood Pressure Measurements at Least Once Post Dose | SBP: Standing, After 3 Minutes: <85 mmHg | 10 percentage of participants |
| Cohort 4: TAK-137 10 mg | Percentage of Participants Who Meet the Takeda Markedly Abnormal Criteria for Blood Pressure Measurements at Least Once Post Dose | SBP: Supine, After 5 Minutes: < 85 mmHg | 10 percentage of participants |
| Cohort 4: TAK-137 10 mg | Percentage of Participants Who Meet the Takeda Markedly Abnormal Criteria for Blood Pressure Measurements at Least Once Post Dose | DBP: Standing, After 1 Minute: <50 mmHg | 0 percentage of participants |
Primary
Percentage of Participants Who Meet the Takeda Markedly Abnormal Criteria for Heart Rate Measurements at Least Once Post Dose
Time frame: Day 1 up to Day 8
Population: Safety analysis set was defined as all participants who received at least one dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohorts 1-4: Placebo | Percentage of Participants Who Meet the Takeda Markedly Abnormal Criteria for Heart Rate Measurements at Least Once Post Dose | 30 percentage of participants |
| Cohort 1: TAK-137 0.5 mg | Percentage of Participants Who Meet the Takeda Markedly Abnormal Criteria for Heart Rate Measurements at Least Once Post Dose | 25 percentage of participants |
| Cohort 2: TAK-137 2 mg | Percentage of Participants Who Meet the Takeda Markedly Abnormal Criteria for Heart Rate Measurements at Least Once Post Dose | 30 percentage of participants |
| Cohort 3: TAK-137 5 mg | Percentage of Participants Who Meet the Takeda Markedly Abnormal Criteria for Heart Rate Measurements at Least Once Post Dose | 22.2 percentage of participants |
| Cohort 4: TAK-137 10 mg | Percentage of Participants Who Meet the Takeda Markedly Abnormal Criteria for Heart Rate Measurements at Least Once Post Dose | 30 percentage of participants |
Primary
Percentage of Participants Who Meet the Takeda Markedly Abnormal Criteria for Pulse Measurements at Least Once Post Dose
Time frame: Day 1 up to Day 8
Population: Safety analysis set was defined as all participants who received at least one dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohorts 1-4: Placebo | Percentage of Participants Who Meet the Takeda Markedly Abnormal Criteria for Pulse Measurements at Least Once Post Dose | Standing, After 3 Minutes: < 50 bpm | 20 percentage of participants |
| Cohorts 1-4: Placebo | Percentage of Participants Who Meet the Takeda Markedly Abnormal Criteria for Pulse Measurements at Least Once Post Dose | Supine, After 5 Minutes: < 50 bpm | 50 percentage of participants |
| Cohorts 1-4: Placebo | Percentage of Participants Who Meet the Takeda Markedly Abnormal Criteria for Pulse Measurements at Least Once Post Dose | Standing, After 3 Minutes: > 120 bpm | 30 percentage of participants |
| Cohorts 1-4: Placebo | Percentage of Participants Who Meet the Takeda Markedly Abnormal Criteria for Pulse Measurements at Least Once Post Dose | Standing, After 1 Minute: < 50 bpm | 10 percentage of participants |
| Cohorts 1-4: Placebo | Percentage of Participants Who Meet the Takeda Markedly Abnormal Criteria for Pulse Measurements at Least Once Post Dose | Standing, After 1 Minute: > 120 bpm | 10 percentage of participants |
| Cohort 1: TAK-137 0.5 mg | Percentage of Participants Who Meet the Takeda Markedly Abnormal Criteria for Pulse Measurements at Least Once Post Dose | Standing, After 3 Minutes: < 50 bpm | 12.5 percentage of participants |
| Cohort 1: TAK-137 0.5 mg | Percentage of Participants Who Meet the Takeda Markedly Abnormal Criteria for Pulse Measurements at Least Once Post Dose | Standing, After 1 Minute: > 120 bpm | 0 percentage of participants |
| Cohort 1: TAK-137 0.5 mg | Percentage of Participants Who Meet the Takeda Markedly Abnormal Criteria for Pulse Measurements at Least Once Post Dose | Standing, After 1 Minute: < 50 bpm | 0 percentage of participants |
| Cohort 1: TAK-137 0.5 mg | Percentage of Participants Who Meet the Takeda Markedly Abnormal Criteria for Pulse Measurements at Least Once Post Dose | Standing, After 3 Minutes: > 120 bpm | 0 percentage of participants |
| Cohort 1: TAK-137 0.5 mg | Percentage of Participants Who Meet the Takeda Markedly Abnormal Criteria for Pulse Measurements at Least Once Post Dose | Supine, After 5 Minutes: < 50 bpm | 37.5 percentage of participants |
| Cohort 2: TAK-137 2 mg | Percentage of Participants Who Meet the Takeda Markedly Abnormal Criteria for Pulse Measurements at Least Once Post Dose | Standing, After 1 Minute: > 120 bpm | 10 percentage of participants |
| Cohort 2: TAK-137 2 mg | Percentage of Participants Who Meet the Takeda Markedly Abnormal Criteria for Pulse Measurements at Least Once Post Dose | Supine, After 5 Minutes: < 50 bpm | 50 percentage of participants |
| Cohort 2: TAK-137 2 mg | Percentage of Participants Who Meet the Takeda Markedly Abnormal Criteria for Pulse Measurements at Least Once Post Dose | Standing, After 1 Minute: < 50 bpm | 0 percentage of participants |
| Cohort 2: TAK-137 2 mg | Percentage of Participants Who Meet the Takeda Markedly Abnormal Criteria for Pulse Measurements at Least Once Post Dose | Standing, After 3 Minutes: < 50 bpm | 20 percentage of participants |
| Cohort 2: TAK-137 2 mg | Percentage of Participants Who Meet the Takeda Markedly Abnormal Criteria for Pulse Measurements at Least Once Post Dose | Standing, After 3 Minutes: > 120 bpm | 10 percentage of participants |
| Cohort 3: TAK-137 5 mg | Percentage of Participants Who Meet the Takeda Markedly Abnormal Criteria for Pulse Measurements at Least Once Post Dose | Standing, After 3 Minutes: > 120 bpm | 0 percentage of participants |
| Cohort 3: TAK-137 5 mg | Percentage of Participants Who Meet the Takeda Markedly Abnormal Criteria for Pulse Measurements at Least Once Post Dose | Supine, After 5 Minutes: < 50 bpm | 22.2 percentage of participants |
| Cohort 3: TAK-137 5 mg | Percentage of Participants Who Meet the Takeda Markedly Abnormal Criteria for Pulse Measurements at Least Once Post Dose | Standing, After 3 Minutes: < 50 bpm | 22.2 percentage of participants |
| Cohort 3: TAK-137 5 mg | Percentage of Participants Who Meet the Takeda Markedly Abnormal Criteria for Pulse Measurements at Least Once Post Dose | Standing, After 1 Minute: > 120 bpm | 0 percentage of participants |
| Cohort 3: TAK-137 5 mg | Percentage of Participants Who Meet the Takeda Markedly Abnormal Criteria for Pulse Measurements at Least Once Post Dose | Standing, After 1 Minute: < 50 bpm | 11.1 percentage of participants |
| Cohort 4: TAK-137 10 mg | Percentage of Participants Who Meet the Takeda Markedly Abnormal Criteria for Pulse Measurements at Least Once Post Dose | Standing, After 1 Minute: > 120 bpm | 40 percentage of participants |
| Cohort 4: TAK-137 10 mg | Percentage of Participants Who Meet the Takeda Markedly Abnormal Criteria for Pulse Measurements at Least Once Post Dose | Standing, After 3 Minutes: < 50 bpm | 0 percentage of participants |
| Cohort 4: TAK-137 10 mg | Percentage of Participants Who Meet the Takeda Markedly Abnormal Criteria for Pulse Measurements at Least Once Post Dose | Supine, After 5 Minutes: < 50 bpm | 40 percentage of participants |
| Cohort 4: TAK-137 10 mg | Percentage of Participants Who Meet the Takeda Markedly Abnormal Criteria for Pulse Measurements at Least Once Post Dose | Standing, After 3 Minutes: > 120 bpm | 50 percentage of participants |
| Cohort 4: TAK-137 10 mg | Percentage of Participants Who Meet the Takeda Markedly Abnormal Criteria for Pulse Measurements at Least Once Post Dose | Standing, After 1 Minute: < 50 bpm | 0 percentage of participants |
Primary
Percentage of Participants Who Meet the Takeda Markedly Abnormal Criteria for Safety Electrocardiogram (ECG) Parameters at Least Once Post Dose
Time frame: Day 1 up to Day 8
Population: Safety analysis set was defined as all participants who received at least one dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohorts 1-4: Placebo | Percentage of Participants Who Meet the Takeda Markedly Abnormal Criteria for Safety Electrocardiogram (ECG) Parameters at Least Once Post Dose | PR Interval: ≤80 msec | 0 percentage of participants |
| Cohorts 1-4: Placebo | Percentage of Participants Who Meet the Takeda Markedly Abnormal Criteria for Safety Electrocardiogram (ECG) Parameters at Least Once Post Dose | PR Interval: ≥200 msec | 0 percentage of participants |
| Cohorts 1-4: Placebo | Percentage of Participants Who Meet the Takeda Markedly Abnormal Criteria for Safety Electrocardiogram (ECG) Parameters at Least Once Post Dose | QRS Interval: ≤80 msec | 10 percentage of participants |
| Cohorts 1-4: Placebo | Percentage of Participants Who Meet the Takeda Markedly Abnormal Criteria for Safety Electrocardiogram (ECG) Parameters at Least Once Post Dose | QT Interval: ≥460 msec | 0 percentage of participants |
| Cohort 1: TAK-137 0.5 mg | Percentage of Participants Who Meet the Takeda Markedly Abnormal Criteria for Safety Electrocardiogram (ECG) Parameters at Least Once Post Dose | QRS Interval: ≤80 msec | 0 percentage of participants |
| Cohort 1: TAK-137 0.5 mg | Percentage of Participants Who Meet the Takeda Markedly Abnormal Criteria for Safety Electrocardiogram (ECG) Parameters at Least Once Post Dose | QT Interval: ≥460 msec | 0 percentage of participants |
| Cohort 1: TAK-137 0.5 mg | Percentage of Participants Who Meet the Takeda Markedly Abnormal Criteria for Safety Electrocardiogram (ECG) Parameters at Least Once Post Dose | PR Interval: ≥200 msec | 25 percentage of participants |
| Cohort 1: TAK-137 0.5 mg | Percentage of Participants Who Meet the Takeda Markedly Abnormal Criteria for Safety Electrocardiogram (ECG) Parameters at Least Once Post Dose | PR Interval: ≤80 msec | 0 percentage of participants |
| Cohort 2: TAK-137 2 mg | Percentage of Participants Who Meet the Takeda Markedly Abnormal Criteria for Safety Electrocardiogram (ECG) Parameters at Least Once Post Dose | QRS Interval: ≤80 msec | 20 percentage of participants |
| Cohort 2: TAK-137 2 mg | Percentage of Participants Who Meet the Takeda Markedly Abnormal Criteria for Safety Electrocardiogram (ECG) Parameters at Least Once Post Dose | PR Interval: ≥200 msec | 30 percentage of participants |
| Cohort 2: TAK-137 2 mg | Percentage of Participants Who Meet the Takeda Markedly Abnormal Criteria for Safety Electrocardiogram (ECG) Parameters at Least Once Post Dose | QT Interval: ≥460 msec | 10 percentage of participants |
| Cohort 2: TAK-137 2 mg | Percentage of Participants Who Meet the Takeda Markedly Abnormal Criteria for Safety Electrocardiogram (ECG) Parameters at Least Once Post Dose | PR Interval: ≤80 msec | 10 percentage of participants |
| Cohort 3: TAK-137 5 mg | Percentage of Participants Who Meet the Takeda Markedly Abnormal Criteria for Safety Electrocardiogram (ECG) Parameters at Least Once Post Dose | PR Interval: ≤80 msec | 0 percentage of participants |
| Cohort 3: TAK-137 5 mg | Percentage of Participants Who Meet the Takeda Markedly Abnormal Criteria for Safety Electrocardiogram (ECG) Parameters at Least Once Post Dose | QT Interval: ≥460 msec | 0 percentage of participants |
| Cohort 3: TAK-137 5 mg | Percentage of Participants Who Meet the Takeda Markedly Abnormal Criteria for Safety Electrocardiogram (ECG) Parameters at Least Once Post Dose | PR Interval: ≥200 msec | 22.2 percentage of participants |
| Cohort 3: TAK-137 5 mg | Percentage of Participants Who Meet the Takeda Markedly Abnormal Criteria for Safety Electrocardiogram (ECG) Parameters at Least Once Post Dose | QRS Interval: ≤80 msec | 22.2 percentage of participants |
| Cohort 4: TAK-137 10 mg | Percentage of Participants Who Meet the Takeda Markedly Abnormal Criteria for Safety Electrocardiogram (ECG) Parameters at Least Once Post Dose | QRS Interval: ≤80 msec | 20 percentage of participants |
| Cohort 4: TAK-137 10 mg | Percentage of Participants Who Meet the Takeda Markedly Abnormal Criteria for Safety Electrocardiogram (ECG) Parameters at Least Once Post Dose | QT Interval: ≥460 msec | 0 percentage of participants |
| Cohort 4: TAK-137 10 mg | Percentage of Participants Who Meet the Takeda Markedly Abnormal Criteria for Safety Electrocardiogram (ECG) Parameters at Least Once Post Dose | PR Interval: ≥200 msec | 10 percentage of participants |
| Cohort 4: TAK-137 10 mg | Percentage of Participants Who Meet the Takeda Markedly Abnormal Criteria for Safety Electrocardiogram (ECG) Parameters at Least Once Post Dose | PR Interval: ≤80 msec | 0 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: Day 1 up to Day 8
Population: Safety analysis set was defined as all participants who received at least one dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohorts 1-4: 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-137 0.5 mg | Percentage of Participants Who Meet the Takeda Markedly Abnormal Criteria for Safety Laboratory Tests at Least Once Post Dose | 12.5 percentage of participants |
| Cohort 2: TAK-137 2 mg | 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-137 5 mg | 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-137 10 mg | Percentage of Participants Who Meet the Takeda Markedly Abnormal Criteria for Safety Laboratory Tests at Least Once Post Dose | 0 percentage of participants |
Secondary
AUC(0-tau): Area Under the Plasma Concentration-time Curve From Time 0 to Time Tau Over the Dosing Interval for TAK-137
Area under the plasma concentration-time curve during a dosing interval, where tau is the length of the dosing interval.
Time frame: Days 1 and 7 pre-dose and at multiple timepoints (up to 24 hours) post-dose
Population: Pharmacokinetic analysis set was defined as all participants who received at least one dose of study drug and had at least one measurable plasma concentration.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohorts 1-4: Placebo | AUC(0-tau): Area Under the Plasma Concentration-time Curve From Time 0 to Time Tau Over the Dosing Interval for TAK-137 | Day 1 (n= 8, 10, 8, 10) | 73.5 nanogram hours per milliliter (ng*hr/mL) | Standard Deviation 37.87 |
| Cohorts 1-4: Placebo | AUC(0-tau): Area Under the Plasma Concentration-time Curve From Time 0 to Time Tau Over the Dosing Interval for TAK-137 | Day 7 (n= 8, 8, 6, 4) | 52.9 nanogram hours per milliliter (ng*hr/mL) | Standard Deviation 24.15 |
| Cohort 1: TAK-137 0.5 mg | AUC(0-tau): Area Under the Plasma Concentration-time Curve From Time 0 to Time Tau Over the Dosing Interval for TAK-137 | Day 7 (n= 8, 8, 6, 4) | 438.4 nanogram hours per milliliter (ng*hr/mL) | Standard Deviation 600.42 |
| Cohort 1: TAK-137 0.5 mg | AUC(0-tau): Area Under the Plasma Concentration-time Curve From Time 0 to Time Tau Over the Dosing Interval for TAK-137 | Day 1 (n= 8, 10, 8, 10) | 265.3 nanogram hours per milliliter (ng*hr/mL) | Standard Deviation 156.89 |
| Cohort 2: TAK-137 2 mg | AUC(0-tau): Area Under the Plasma Concentration-time Curve From Time 0 to Time Tau Over the Dosing Interval for TAK-137 | Day 1 (n= 8, 10, 8, 10) | 717.1 nanogram hours per milliliter (ng*hr/mL) | Standard Deviation 432.37 |
| Cohort 2: TAK-137 2 mg | AUC(0-tau): Area Under the Plasma Concentration-time Curve From Time 0 to Time Tau Over the Dosing Interval for TAK-137 | Day 7 (n= 8, 8, 6, 4) | 1224.0 nanogram hours per milliliter (ng*hr/mL) | Standard Deviation 689.8 |
| Cohort 3: TAK-137 5 mg | AUC(0-tau): Area Under the Plasma Concentration-time Curve From Time 0 to Time Tau Over the Dosing Interval for TAK-137 | Day 1 (n= 8, 10, 8, 10) | 1442.8 nanogram hours per milliliter (ng*hr/mL) | Standard Deviation 621.57 |
| Cohort 3: TAK-137 5 mg | AUC(0-tau): Area Under the Plasma Concentration-time Curve From Time 0 to Time Tau Over the Dosing Interval for TAK-137 | Day 7 (n= 8, 8, 6, 4) | 3288.5 nanogram hours per milliliter (ng*hr/mL) | Standard Deviation 3189.13 |
Secondary
Cmax: Maximum Observed Plasma Concentration for TAK-137
Maximum observed plasma concentration (Cmax) is the peak plasma concentration of a drug after administration, obtained directly from the plasma concentration-time curve.
Time frame: Day 1 pre-dose and at multiple timepoints (up to 24 hours) post-dose
Population: Pharmacokinetic analysis set was defined as all participants who received at least one dose of study drug and had at least one measurable plasma concentration.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohorts 1-4: Placebo | Cmax: Maximum Observed Plasma Concentration for TAK-137 | 8.32 nanogram per milliliter (ng/mL) | Standard Deviation 2.651 |
| Cohort 1: TAK-137 0.5 mg | Cmax: Maximum Observed Plasma Concentration for TAK-137 | 28.04 nanogram per milliliter (ng/mL) | Standard Deviation 7.554 |
| Cohort 2: TAK-137 2 mg | Cmax: Maximum Observed Plasma Concentration for TAK-137 | 64.91 nanogram per milliliter (ng/mL) | Standard Deviation 24.592 |
| Cohort 3: TAK-137 5 mg | Cmax: Maximum Observed Plasma Concentration for TAK-137 | 103.13 nanogram per milliliter (ng/mL) | Standard Deviation 27.822 |
Secondary
Cmax, ss: Maximum Observed Plasma Concentration at Steady State for TAK-137
Maximum observed steady-state plasma concentration during a dosing interval.
Time frame: Day 7 pre-dose and at multiple timepoints (up to 24 hours) post-dose
Population: Pharmacokinetic analysis set was defined as all participants who received at least one dose of study drug and had at least one measurable plasma concentration.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohorts 1-4: Placebo | Cmax, ss: Maximum Observed Plasma Concentration at Steady State for TAK-137 | 7.79 ng/mL | Standard Deviation 2.039 |
| Cohort 1: TAK-137 0.5 mg | Cmax, ss: Maximum Observed Plasma Concentration at Steady State for TAK-137 | 38.01 ng/mL | Standard Deviation 22.749 |
| Cohort 2: TAK-137 2 mg | Cmax, ss: Maximum Observed Plasma Concentration at Steady State for TAK-137 | 86.25 ng/mL | Standard Deviation 35.079 |
| Cohort 3: TAK-137 5 mg | Cmax, ss: Maximum Observed Plasma Concentration at Steady State for TAK-137 | 176.25 ng/mL | Standard Deviation 113.096 |
Secondary
Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-137
Tmax: Time to reach the maximum plasma concentration (Cmax), equal to time (hours) to Cmax.
Time frame: Days 1 and 7 pre-dose and at multiple timepoints (up to 24 hours) post-dose
Population: Pharmacokinetic analysis set was defined as all participants who received at least one dose of study drug and had at least one measurable plasma concentration.
| Arm | Measure | Group | Value (MEDIAN) | Dispersion |
|---|---|---|---|---|
| Cohorts 1-4: Placebo | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-137 | Day 1 (n= 8, 10, 8, 10) | 1.560 hours | Full Range 2.039 |
| Cohorts 1-4: Placebo | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-137 | Day 7 (n= 8, 8, 6, 6) | 1.015 hours | — |
| Cohort 1: TAK-137 0.5 mg | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-137 | Day 7 (n= 8, 8, 6, 6) | 1.750 hours | — |
| Cohort 1: TAK-137 0.5 mg | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-137 | Day 1 (n= 8, 10, 8, 10) | 1.750 hours | Full Range 22.749 |
| Cohort 2: TAK-137 2 mg | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-137 | Day 1 (n= 8, 10, 8, 10) | 2.060 hours | Full Range 35.079 |
| Cohort 2: TAK-137 2 mg | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-137 | Day 7 (n= 8, 8, 6, 6) | 3.500 hours | — |
| Cohort 3: TAK-137 5 mg | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-137 | Day 1 (n= 8, 10, 8, 10) | 4.000 hours | Full Range 113.096 |
| Cohort 3: TAK-137 5 mg | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-137 | Day 7 (n= 8, 8, 6, 6) | 2.000 hours | — |