Healthy Volunteers
Conditions
Keywords
Drug Therapy
Brief summary
The purpose of this study is to characterize the safety and tolerability profile of TAK-935 in healthy participants when administered as a single dose of oral solution at escalating dose levels.
Detailed description
The drug being tested in this study is TAK-935. TAK-935 is being tested to find a safe and well-tolerated dose and to assess how TAK-935 is processed by the body. This study will look at side effects and lab results in people who take TAK-935 and is designed as a randomized dose-rising study. The study will consist of 6 Cohorts with 8 participants in each Cohort. In each Cohort, 6 participants will receive a single dose of TAK-935 and 2 participants will receive placebo after a 10-hour fast. The starting dose will be 15 mg followed by planned doses of 50, 200, 600, 900 and not to exceed 1350 mg in subsequent cohorts. This single-center trial will be conducted in the United States. The overall time to participate in this study is up to 51 days. Participants will make 2 visits to the clinic, including one 7-day period of confinement to the clinic. All participants will be contacted by telephone 14 days after the dose of study drug 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
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
19 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
1. Is a healthy male or female adult who is 19 to 55 years of age inclusive at the time of informed consent. 2. Weighs at least 45 kg and has a body mass index (BMI) between 18.0 and 30.0 kg/m\^2, inclusive at the Screening Visit.
Exclusion criteria
1. Has uncontrolled, clinically significant neurological (including seizure disorders), cardiovascular, pulmonary, hepatic, renal, metabolic, gastrointestinal, urological, immunologic, endocrine disease, or psychiatric disorder, or other abnormality. 2. Has a known hypersensitivity to any component of the formulation of TAK-935. 3. There is any finding in the participant's medical history, significant results from physical examination, or safety laboratory tests.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Experience at Least One Treatment-emergent Adverse Event (TEAE) | Day 1 to Day 30 | 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 (eg, 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 and within 30 days after the last dose of study drug. |
| Percentage of Participants Who Meet the Markedly Abnormal Criteria, for Safety Laboratory Tests at Least Once Post-dose | Day 1 to Day 14 | The percentage of participants with any markedly abnormal standard safety laboratory values (hematology, serum chemistries, and urinalysis) collected during the treatment period. |
| Percentage of Participants Who Meet Markedly Abnormal Criteria, for Vital Sign Measurements at Least Once Post-dose | Day 1 to Day 14 | The percentage of participants with any markedly abnormal vital signs (oral temperature, respiration rate, pulse, and blood pressure) collected during the treatment period. |
| Percentage of Participants Who Meet the Markedly Abnormal Criteria, for Electrocardiogram (ECG) Measurements at Least Once Post-dose | Day 1 to Day 14 | The percentage of participants with any markedly abnormal criteria for standard 12-lead ECG measured collected during the treatment period. |
Secondary
| Measure | Time frame |
|---|---|
| Cmax: Maximum Observed Plasma Concentration for TAK-935 | Multiple time-points (Up to 96 hours) post-dose |
| AUClast: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-935 | Multiple time-points (Up to 96 hours) post-dose |
| AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity of TAK-935 | Multiple time-points (Up to 96 hours) post-dose |
Countries
United States
Contacts
STUDY_DIRECTORMedical Director Clinical Science
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 09 July 2014 to 30 July 2015.
Pre-assignment details
Healthy Volunteers were enrolled in 1 of 7 treatment groups, once a day placebo, TAK 935 15 mg, 50 mg, 200 mg, 600 mg, 900 mg or 1350 mg.
Participants by arm
| Arm | Count |
|---|---|
| Cohorts 1-6: Placebo TAK-935 placebo-matching solution, orally, once, on Day 1. | 12 |
| Cohort 1: TAK-935 15 mg TAK-935 15 mg solution, orally, once, on Day 1. | 6 |
| Cohort 2: TAK-935 50 mg TAK-935 50 mg solution, orally, once, on Day 1. | 6 |
| Cohort 3: TAK-935 200 mg TAK-935 200 mg solution, orally, once, on Day 1. | 6 |
| Cohort 4: TAK-935 600 mg TAK-935 600 mg solution, orally, once, on Day 1. | 6 |
| Cohort 5: TAK-935 900 mg TAK-935 900 mg solution, orally, once, on Day 1. | 6 |
| Cohort 6: TAK-935 1350 mg TAK-935 1350 mg solution, orally, once, on Day 1. | 6 |
| Total | 48 |
Baseline characteristics
| Characteristic | Cohort 1: TAK-935 15 mg | Cohort 2: TAK-935 50 mg | Cohort 3: TAK-935 200 mg | Cohort 4: TAK-935 600 mg | Cohort 5: TAK-935 900 mg | Cohort 6: TAK-935 1350 mg | Cohorts 1-6: Placebo | Total |
|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 34.2 years STANDARD_DEVIATION 8.21 | 34.3 years STANDARD_DEVIATION 10.93 | 29.8 years STANDARD_DEVIATION 6.74 | 35.3 years STANDARD_DEVIATION 13.31 | 30.5 years STANDARD_DEVIATION 10.33 | 32.8 years STANDARD_DEVIATION 12.97 | 35.9 years STANDARD_DEVIATION 10.41 | 33.6 years STANDARD_DEVIATION 10.15 |
| Body Mass Index (BMI) | 24.86 kg/m^2 STANDARD_DEVIATION 4.073 | 25.44 kg/m^2 STANDARD_DEVIATION 3.361 | 25.05 kg/m^2 STANDARD_DEVIATION 3.039 | 25.51 kg/m^2 STANDARD_DEVIATION 2.539 | 26.88 kg/m^2 STANDARD_DEVIATION 2.313 | 25.34 kg/m^2 STANDARD_DEVIATION 4.251 | 24.00 kg/m^2 STANDARD_DEVIATION 2.532 | 25.13 kg/m^2 STANDARD_DEVIATION 3.064 |
| Height | 165.0 cm STANDARD_DEVIATION 11.52 | 175.0 cm STANDARD_DEVIATION 5.59 | 178.7 cm STANDARD_DEVIATION 7.31 | 173.5 cm STANDARD_DEVIATION 8.89 | 161.5 cm STANDARD_DEVIATION 2.88 | 165.5 cm STANDARD_DEVIATION 2.59 | 170.8 cm STANDARD_DEVIATION 5.99 | 170.1 cm STANDARD_DEVIATION 8.43 |
| Race/Ethnicity, Customized Black or African American | 0 participants | 1 participants | 0 participants | 2 participants | 2 participants | 1 participants | 2 participants | 8 participants |
| Race/Ethnicity, Customized Hispanic or Latino | 2 participants | 1 participants | 0 participants | 0 participants | 0 participants | 0 participants | 1 participants | 4 participants |
| Race/Ethnicity, Customized Multiracial | 0 participants | 0 participants | 0 participants | 1 participants | 0 participants | 0 participants | 0 participants | 1 participants |
| Race/Ethnicity, Customized Non-Hispanic or Latino | 4 participants | 5 participants | 6 participants | 6 participants | 6 participants | 6 participants | 11 participants | 44 participants |
| Race/Ethnicity, Customized White | 6 participants | 5 participants | 6 participants | 3 participants | 4 participants | 5 participants | 10 participants | 39 participants |
| Region of Enrollment United States | 6 participants | 6 participants | 6 participants | 6 participants | 6 participants | 6 participants | 12 participants | 48 participants |
| Sex: Female, Male Female | 3 Participants | 0 Participants | 0 Participants | 2 Participants | 6 Participants | 6 Participants | 5 Participants | 22 Participants |
| Sex: Female, Male Male | 3 Participants | 6 Participants | 6 Participants | 4 Participants | 0 Participants | 0 Participants | 7 Participants | 26 Participants |
| Weight | 68.88 kg STANDARD_DEVIATION 19.873 | 78.25 kg STANDARD_DEVIATION 13.623 | 80.18 kg STANDARD_DEVIATION 12.039 | 76.85 kg STANDARD_DEVIATION 9.465 | 70.10 kg STANDARD_DEVIATION 6.214 | 69.28 kg STANDARD_DEVIATION 10.981 | 70.23 kg STANDARD_DEVIATION 10.478 | 73.00 kg STANDARD_DEVIATION 12.178 |
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 | EG006 affected / at risk |
|---|---|---|---|---|---|---|---|
| other Total, other adverse events | 5 / 12 | 2 / 6 | 1 / 6 | 2 / 6 | 5 / 6 | 2 / 6 | 2 / 6 |
| serious Total, serious adverse events | 0 / 12 | 0 / 6 | 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)
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 (eg, 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 and within 30 days after the last dose of study drug.
Time frame: Day 1 to Day 30
Population: Safety set included all participants who were enrolled and received study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohorts 1-6: Placebo | Percentage of Participants Who Experience at Least One Treatment-emergent Adverse Event (TEAE) | 41.7 percentage of participants |
| Cohort 1: TAK-935 15 mg | Percentage of Participants Who Experience at Least One Treatment-emergent Adverse Event (TEAE) | 33.3 percentage of participants |
| Cohort 2: TAK-935 50 mg | Percentage of Participants Who Experience at Least One Treatment-emergent Adverse Event (TEAE) | 16.7 percentage of participants |
| Cohort 3: TAK-935 200 mg | Percentage of Participants Who Experience at Least One Treatment-emergent Adverse Event (TEAE) | 33.3 percentage of participants |
| Cohort 4: TAK-935 600 mg | Percentage of Participants Who Experience at Least One Treatment-emergent Adverse Event (TEAE) | 83.3 percentage of participants |
| Cohort 5: TAK-935 900 mg | Percentage of Participants Who Experience at Least One Treatment-emergent Adverse Event (TEAE) | 33.3 percentage of participants |
| Cohort 6: TAK-935 1350 mg | Percentage of Participants Who Experience at Least One Treatment-emergent Adverse Event (TEAE) | 33.3 percentage of participants |
Primary
Percentage of Participants Who Meet Markedly Abnormal Criteria, for Vital Sign Measurements at Least Once Post-dose
The percentage of participants with any markedly abnormal vital signs (oral temperature, respiration rate, pulse, and blood pressure) collected during the treatment period.
Time frame: Day 1 to Day 14
Population: Safety set included all participants who were enrolled and received study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohorts 1-6: Placebo | Percentage of Participants Who Meet Markedly Abnormal Criteria, for Vital Sign Measurements at Least Once Post-dose | 75.0 percentage of participants |
| Cohort 1: TAK-935 15 mg | Percentage of Participants Who Meet Markedly Abnormal Criteria, for Vital Sign Measurements at Least Once Post-dose | 100 percentage of participants |
| Cohort 2: TAK-935 50 mg | Percentage of Participants Who Meet Markedly Abnormal Criteria, for Vital Sign Measurements at Least Once Post-dose | 66.7 percentage of participants |
| Cohort 3: TAK-935 200 mg | Percentage of Participants Who Meet Markedly Abnormal Criteria, for Vital Sign Measurements at Least Once Post-dose | 66.7 percentage of participants |
| Cohort 4: TAK-935 600 mg | Percentage of Participants Who Meet Markedly Abnormal Criteria, for Vital Sign Measurements at Least Once Post-dose | 66.7 percentage of participants |
| Cohort 5: TAK-935 900 mg | Percentage of Participants Who Meet Markedly Abnormal Criteria, for Vital Sign Measurements at Least Once Post-dose | 66.7 percentage of participants |
| Cohort 6: TAK-935 1350 mg | Percentage of Participants Who Meet Markedly Abnormal Criteria, for Vital Sign Measurements at Least Once Post-dose | 66.7 percentage of participants |
Primary
Percentage of Participants Who Meet the Markedly Abnormal Criteria, for Electrocardiogram (ECG) Measurements at Least Once Post-dose
The percentage of participants with any markedly abnormal criteria for standard 12-lead ECG measured collected during the treatment period.
Time frame: Day 1 to Day 14
Population: Safety set included all participants who were enrolled and received study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohorts 1-6: Placebo | Percentage of Participants Who Meet the Markedly Abnormal Criteria, for Electrocardiogram (ECG) Measurements at Least Once Post-dose | 25.0 percentage of participants |
| Cohort 1: TAK-935 15 mg | Percentage of Participants Who Meet the Markedly Abnormal Criteria, for Electrocardiogram (ECG) Measurements at Least Once Post-dose | 66.7 percentage of participants |
| Cohort 2: TAK-935 50 mg | Percentage of Participants Who Meet the Markedly Abnormal Criteria, for Electrocardiogram (ECG) Measurements at Least Once Post-dose | 83.3 percentage of participants |
| Cohort 3: TAK-935 200 mg | Percentage of Participants Who Meet the Markedly Abnormal Criteria, for Electrocardiogram (ECG) Measurements at Least Once Post-dose | 50.0 percentage of participants |
| Cohort 4: TAK-935 600 mg | Percentage of Participants Who Meet the Markedly Abnormal Criteria, for Electrocardiogram (ECG) Measurements at Least Once Post-dose | 16.7 percentage of participants |
| Cohort 5: TAK-935 900 mg | Percentage of Participants Who Meet the Markedly Abnormal Criteria, for Electrocardiogram (ECG) Measurements at Least Once Post-dose | 33.3 percentage of participants |
| Cohort 6: TAK-935 1350 mg | Percentage of Participants Who Meet the Markedly Abnormal Criteria, for Electrocardiogram (ECG) Measurements at Least Once Post-dose | 33.3 percentage of participants |
Primary
Percentage of Participants Who Meet the Markedly Abnormal Criteria, for Safety Laboratory Tests at Least Once Post-dose
The percentage of participants with any markedly abnormal standard safety laboratory values (hematology, serum chemistries, and urinalysis) collected during the treatment period.
Time frame: Day 1 to Day 14
Population: Safety set included all participants who were enrolled and received study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohorts 1-6: Placebo | Percentage of Participants Who Meet the Markedly Abnormal Criteria, for Safety Laboratory Tests at Least Once Post-dose | 16.7 percentage of participants |
| Cohort 1: TAK-935 15 mg | Percentage of Participants Who Meet the Markedly Abnormal Criteria, for Safety Laboratory Tests at Least Once Post-dose | 0 percentage of participants |
| Cohort 2: TAK-935 50 mg | Percentage of Participants Who Meet the Markedly Abnormal Criteria, for Safety Laboratory Tests at Least Once Post-dose | 0 percentage of participants |
| Cohort 3: TAK-935 200 mg | Percentage of Participants Who Meet the Markedly Abnormal Criteria, for Safety Laboratory Tests at Least Once Post-dose | 0 percentage of participants |
| Cohort 4: TAK-935 600 mg | Percentage of Participants Who Meet the Markedly Abnormal Criteria, for Safety Laboratory Tests at Least Once Post-dose | 0 percentage of participants |
| Cohort 5: TAK-935 900 mg | Percentage of Participants Who Meet the Markedly Abnormal Criteria, for Safety Laboratory Tests at Least Once Post-dose | 16.7 percentage of participants |
| Cohort 6: TAK-935 1350 mg | Percentage of Participants Who Meet the Markedly Abnormal Criteria, for Safety Laboratory Tests at Least Once Post-dose | 0 percentage of participants |
Secondary
AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity of TAK-935
Time frame: Multiple time-points (Up to 96 hours) post-dose
Population: PK set included all participants in the safety set who had at least 1 measurable plasma or urine concentration.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohorts 1-6: Placebo | AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity of TAK-935 | 23.290 ng*hr/mL | Standard Deviation 6.7061 |
| Cohort 1: TAK-935 15 mg | AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity of TAK-935 | 172.430 ng*hr/mL | Standard Deviation 107.0799 |
| Cohort 2: TAK-935 50 mg | AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity of TAK-935 | 621.369 ng*hr/mL | Standard Deviation 240.5953 |
| Cohort 3: TAK-935 200 mg | AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity of TAK-935 | 5809.066 ng*hr/mL | Standard Deviation 3427.5393 |
| Cohort 4: TAK-935 600 mg | AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity of TAK-935 | 7660.961 ng*hr/mL | Standard Deviation 1962.0905 |
| Cohort 5: TAK-935 900 mg | AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity of TAK-935 | 13541.772 ng*hr/mL | Standard Deviation 5763.4722 |
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: Multiple time-points (Up to 96 hours) post-dose
Population: PK set included all participants in the safety set who had at least 1 measurable plasma or urine concentration.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohorts 1-6: Placebo | AUClast: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-935 | 33.323 ng*hr/mL | Standard Deviation 28.9569 |
| Cohort 1: TAK-935 15 mg | AUClast: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-935 | 168.736 ng*hr/mL | Standard Deviation 88.3702 |
| Cohort 2: TAK-935 50 mg | AUClast: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-935 | 562.660 ng*hr/mL | Standard Deviation 196.6517 |
| Cohort 3: TAK-935 200 mg | AUClast: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-935 | 5791.561 ng*hr/mL | Standard Deviation 3427.9888 |
| Cohort 4: TAK-935 600 mg | AUClast: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-935 | 7619.088 ng*hr/mL | Standard Deviation 1928.2091 |
| Cohort 5: TAK-935 900 mg | AUClast: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-935 | 13501.049 ng*hr/mL | Standard Deviation 5778.0847 |
Secondary
Cmax: Maximum Observed Plasma Concentration for TAK-935
Time frame: Multiple time-points (Up to 96 hours) post-dose
Population: Pharmacokinetic (PK) set included all participants in the safety set who had at least 1 measurable plasma or urine concentration.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohorts 1-6: Placebo | Cmax: Maximum Observed Plasma Concentration for TAK-935 | 43.533 ng/mL | Standard Deviation 41.235 |
| Cohort 1: TAK-935 15 mg | Cmax: Maximum Observed Plasma Concentration for TAK-935 | 210.150 ng/mL | Standard Deviation 153.0463 |
| Cohort 2: TAK-935 50 mg | Cmax: Maximum Observed Plasma Concentration for TAK-935 | 571.167 ng/mL | Standard Deviation 257.8002 |
| Cohort 3: TAK-935 200 mg | Cmax: Maximum Observed Plasma Concentration for TAK-935 | 4551.667 ng/mL | Standard Deviation 2573.5067 |
| Cohort 4: TAK-935 600 mg | Cmax: Maximum Observed Plasma Concentration for TAK-935 | 5080.000 ng/mL | Standard Deviation 1801.9323 |
| Cohort 5: TAK-935 900 mg | Cmax: Maximum Observed Plasma Concentration for TAK-935 | 7953.333 ng/mL | Standard Deviation 2151.3035 |