Healthy Volunteers
Conditions
Keywords
Drug Therapy
Brief summary
The purpose of this study is to assess the relative bioavailability (BA) of 300 milligram (mg) TAK-935 tablets compared to 300 mg of TAK-935 solution and to determine the effect of food on the BA of TAK-935 300 mg tablets in healthy adult participants.
Detailed description
The drug being tested in this study is called TAK-935. The study will look at the relative BA of TAK-935 300 mg tablets compared to a TAK-935 300 mg oral solution and will assess the effect of food on the BA of TAK-935 300 mg tablets in healthy adult participants. The study will enroll approximately 9 participants. Participants will be randomly assigned (by chance, like flipping a coin) to one of the 3 treatment sequences: * TAK-935 (300 mg Tablets Fed + 300 mg Tablets Fasted + 300 mg Solution Fasted) * TAK-935 (300 mg Tablets Fasted + 300 mg Solution Fasted + 300 mg Tablets Fed) * TAK-935 (300 mg Solution Fasted + 300 mg Tablets Fed + 300 mg Tablets Fasted) Administration of each dose will be separated by a washout period of at least 3 days. Participants will be asked to take single dose of TAK-935 tablet or oral solution on Day 1 of each Intervention Period. This single center trial will be conducted in the United States. The overall time to participate in this study is 39 days. Participants will remain confined to the clinic from Day 1 of Intervention Period 1 to Day 3 of Intervention Period 3 and will be contacted by telephone 30 days after last dose of TAK-935 for a follow-up assessment.
Interventions
DRUGTAK-935 Tablets
Tablets
DRUGTAK-935 Oral Solution
Oral solution
Sponsors
Takeda
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
1\. 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 -2.
Exclusion criteria
1. Has received TAK-935 in a previous clinical study or as a therapeutic agent. 2. Has a history of any psychiatric disorder as diagnosed utilizing Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM 5) criteria. 3. Has any lifetime history of drug abuse (defined as any illicit drug use) or any lifetime history of alcohol abuse 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. 4. Has a history of cancer, except basal cell carcinoma which has been in remission for at least 5 years prior to Day 1. 5. Has a positive test result for hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibody, human immunodeficiency virus (HIV) antibody at Screening or a known history of human immunodeficiency virus infection. 6. 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. Cotinine test is positive at Screening or Check-In (Day -1). 7. Has poor peripheral venous access. 8. Has donated or lost 450 milliliter (mL) or more of his or her blood volume (including plasmapheresis), or had a transfusion of any blood product within 30 days prior to Day 1 of Period 1.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Cmax: Maximum Observed Plasma Concentration for TAK-935 | Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose |
| AUCt: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-935 | Day 1 pre-dose and at multiple time points (up to 48 hours) 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 48 hours) post-dose |
Secondary
| Measure | Time frame |
|---|---|
| Percentage of Participants Who Experience at Least One Treatment Emergent Adverse Event (TEAE) | Baseline up to 30 days after last dose of study drug (Day 39) |
| Percentage of Participants Who Meet the Markedly Abnormal Criteria for Safety Laboratory Tests at Least Once Post Dose | Baseline up to Day 11 |
| Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post Dose. | Baseline up to Day 11 |
| Percentage of Participants Who Meet the Markedly Abnormal Criteria for Safety Electrocardiogram (ECG) Parameters at Least Once Post Dose | Baseline up to Day 11 |
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 12 September 2016 to 09 November 2016.
Pre-assignment details
Healthy participants were enrolled in 1 of the 3 treatment sequences that determined the order of the three treatments received: TAK-935 300 milligram (mg) tablets in fasted state, TAK-935 300 mg tablets in fed state and TAK-935 300 mg solution in fasted state.
Participants by arm
| Arm | Count |
|---|---|
| TAK-935 300 mg: Tablets Fed + Tablets Fasted + Solution Fasted TAK-935 3\*100 mg, tablets, orally, 30 minutes after starting ingestion of a high-fat meal, once on Day 1 of Intervention Period 1, followed by a minimum 3-day washout period, further followed by TAK-935 3\*100 mg, tablets, orally, after a 10-hour fast, once on Day 1 of Intervention Period 2, followed by a minimum 3-day washout period, further followed by TAK-935 300 mg, solution, orally, after a 10-hour fast, once on Day 1 of Intervention Period 3. | 3 |
| TAK-935 300 mg: Tablets Fasted + Solution Fasted + Tablets Fed TAK-935 3\*100 mg, tablets, orally, after a 10-hour fast, once on Day 1 of Intervention Period 1, followed by a minimum 3-day washout period, further followed by TAK-935 300 mg, solution, orally, after a 10-hour fast, once on Day 1 of Intervention Period 2, followed by a minimum 3-day washout period, further followed by TAK-935 3\*100 mg, tablets, orally, 30 minutes after starting ingestion of a high-fat meal, once on Day 1 of Intervention Period 3. | 3 |
| TAK 935 300 mg: Solution Fasted + Tablets Fed + Tablets Fasted TAK-935 300 mg, solution, orally, after a 10-hour fast, once on Day 1 of Intervention Period 1, followed by a minimum 3-day washout period, further followed by TAK-935 3\*100 mg, tablets, orally, 30 minutes after starting ingestion of a high-fat meal, once on Day 1 of Intervention Period 2, followed by a minimum 3-day washout period, further followed by TAK-935 3\*100 mg, tablets, orally, after a 10-hour fast, once on Day 1 of Intervention Period 3. | 3 |
| Total | 9 |
Baseline characteristics
| Characteristic | Total | TAK 935 300 mg: Solution Fasted + Tablets Fed + Tablets Fasted | TAK-935 300 mg: Tablets Fasted + Solution Fasted + Tablets Fed | TAK-935 300 mg: Tablets Fed + Tablets Fasted + Solution Fasted |
|---|---|---|---|---|
| Age, Continuous | 36.7 years STANDARD_DEVIATION 8 | 35.7 years STANDARD_DEVIATION 13.58 | 37.0 years STANDARD_DEVIATION 3 | 37.3 years STANDARD_DEVIATION 7.77 |
| Body Mass Index (BMI) | 26.46 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 2.43 | 24.62 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 3.295 | 26.75 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 0.889 | 28.01 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 1.784 |
| Female Reproductive Status Having childbearing potential | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Female Reproductive Status Not applicable | 7 Participants | 2 Participants | 3 Participants | 2 Participants |
| Female Reproductive Status Postmenopausal | 1 Participants | 1 Participants | 0 Participants | 0 Participants |
| Height | 171.1 centimeter (cm) STANDARD_DEVIATION 3.44 | 170.3 centimeter (cm) STANDARD_DEVIATION 1.53 | 171.0 centimeter (cm) STANDARD_DEVIATION 2 | 172.0 centimeter (cm) STANDARD_DEVIATION 6.24 |
| No Alcohol Consumption | 9 Participants | 3 Participants | 3 Participants | 3 Participants |
| No Xanthine/Caffeine Consumption | 9 Participants | 3 Participants | 3 Participants | 3 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 5 Participants | 0 Participants | 2 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 3 Participants | 2 Participants | 1 Participants | 0 Participants |
| Region of Enrollment United States | 9 Participants | 3 Participants | 3 Participants | 3 Participants |
| Sex: Female, Male Female | 2 Participants | 1 Participants | 0 Participants | 1 Participants |
| Sex: Female, Male Male | 7 Participants | 2 Participants | 3 Participants | 2 Participants |
| Smoking Classification Ex-smoker | 2 Participants | 0 Participants | 1 Participants | 1 Participants |
| Smoking Classification Never smoked | 7 Participants | 3 Participants | 2 Participants | 2 Participants |
| Weight | 77.62 kilogram (kg) STANDARD_DEVIATION 9.039 | 71.50 kilogram (kg) STANDARD_DEVIATION 10.096 | 78.20 kilogram (kg) STANDARD_DEVIATION 1.311 | 83.17 kilogram (kg) STANDARD_DEVIATION 10.97 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 9 | 0 / 9 | 0 / 9 |
| other Total, other adverse events | 0 / 9 | 2 / 9 | 0 / 9 |
| serious Total, serious adverse events | 0 / 9 | 0 / 9 | 0 / 9 |
Outcome results
Primary
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 48 hours) post-dose
Population: The PK analysis set where data on Day 1 was available. The PK set included all participants who were enrolled, received study drug and had at least 1 measurable plasma concentration for either TAK-935 or its M-I.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| TAK-935 300 mg Tablets Fed | AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-935 | 1182.641 ng*hr/mL | Standard Deviation 385.6485 |
| TAK-935 300 mg Tablets Fasted | AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-935 | 1369.963 ng*hr/mL | Standard Deviation 523.2334 |
| TAK-935 300 mg Solution Fasted | AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-935 | 1564.307 ng*hr/mL | Standard Deviation 743.3798 |
Comparison: ANOVA was performed on natural logarithms of TAK-935 AUC∞ with fixed factors of sequence, period, and regimen and random factor of participant nested within sequence. Pairwise comparisons was used to assess relative BA of TAK-935 tablet to solution. Point estimate and 90% CI in original scale were obtained by exponentiation of differences in natural-log scale.p-value: 0.19190% CI: [0.676, 1.05]ANOVA
Comparison: ANOVA was performed on natural logarithms of TAK-935 AUC∞ with factors of sequence, period, and regimen and random factor of participant nested within sequence. Pairwise comparisons was used to assess relative BA of TAK-935 administered after high-fat meal versus fasted. Point estimate and its 90% CI in original scale were obtained by exponentiation of differences in natural-log scale.p-value: 0.35590% CI: [0.726, 1.1]ANOVA
Primary
AUCt: 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 pre-dose and at multiple time points (up to 48 hours) post-dose
Population: The PK set included all participants who were enrolled, received study drug and had at least 1 measurable plasma concentration for either TAK-935 or its M-I.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| TAK-935 300 mg Tablets Fed | AUCt: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-935 | 1170.954 nanogram hours per milliliter (ng*hr/mL) | Standard Deviation 386.1425 |
| TAK-935 300 mg Tablets Fasted | AUCt: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-935 | 1328.482 nanogram hours per milliliter (ng*hr/mL) | Standard Deviation 496.8168 |
| TAK-935 300 mg Solution Fasted | AUCt: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-935 | 1601.806 nanogram hours per milliliter (ng*hr/mL) | Standard Deviation 711.7143 |
Comparison: ANOVA was performed on natural logarithms of TAK-935 AUCt with fixed factors of sequence, period, and regimen and random factor of participant nested within sequence. Pairwise comparisons was used to assess relative BA of TAK-935 tablet to solution. Point estimate and 90% CI in original scale were obtained by exponentiation of differences in natural-log scale.p-value: 0.14690% CI: [0.706, 1.024]ANOVA
Comparison: ANOVA was performed on natural logarithms of TAK-935 AUCt with factors of sequence, period, and regimen and random factor of participant nested within sequence. Pairwise comparisons was used to assess relative BA of TAK-935 administered after high-fat meal versus fasted. Point estimate and its 90% CI in original scale were obtained by exponentiation of differences in natural-log scale.p-value: 0.28190% CI: [0.738, 1.07]ANOVA
Primary
Cmax: Maximum Observed Plasma Concentration for TAK-935
Time frame: Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose
Population: The pharmacokinetic (PK) set included all participants who were enrolled, received study drug and had at least 1 measurable plasma concentration for either TAK-935 or its metabolite (M-I).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| TAK-935 300 mg Tablets Fed | Cmax: Maximum Observed Plasma Concentration for TAK-935 | 477.000 nanogram per milliliter (ng/mL) | Standard Deviation 298.0705 |
| TAK-935 300 mg Tablets Fasted | Cmax: Maximum Observed Plasma Concentration for TAK-935 | 1150.889 nanogram per milliliter (ng/mL) | Standard Deviation 710.594 |
| TAK-935 300 mg Solution Fasted | Cmax: Maximum Observed Plasma Concentration for TAK-935 | 1882.000 nanogram per milliliter (ng/mL) | Standard Deviation 1250.7022 |
Comparison: Analysis of variance (ANOVA) was performed on natural logarithms of TAK-935 Cmax with fixed factors of sequence, period and regimen, and random factor of participant nested within sequence. Pairwise comparisons was used to assess relative bioavailability (BA) of TAK-935 tablet to solution. Point estimate and 90 percent (%) confidence interval (CI) in original scale were obtained by exponentiation of differences in natural-log scale.p-value: 0.07990% CI: [0.411, 0.969]ANOVA
Comparison: ANOVA was performed on natural logarithms of TAK-935 Cmax with fixed factors of sequence, period, and regimen and random factor of participant nested within sequence. Pairwise comparisons was used to assess relative BA of TAK-935 administered after high-fat meal versus fasted. Point estimate and its 90% confidence interval in original scale were obtained by exponentiation of differences in natural-log scale.p-value: 0.00290% CI: [0.262, 0.618]ANOVA
Secondary
Percentage of Participants Who Experience at Least One Treatment Emergent Adverse Event (TEAE)
Time frame: Baseline up to 30 days after last dose of study drug (Day 39)
Population: The safety analysis set included all participants who were enrolled and received study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TAK-935 300 mg Tablets Fed | Percentage of Participants Who Experience at Least One Treatment Emergent Adverse Event (TEAE) | 0 percentage of participants |
| TAK-935 300 mg Tablets Fasted | Percentage of Participants Who Experience at Least One Treatment Emergent Adverse Event (TEAE) | 22.2 percentage of participants |
| TAK-935 300 mg Solution Fasted | Percentage of Participants Who Experience at Least One Treatment Emergent Adverse Event (TEAE) | 0 percentage of participants |
Secondary
Percentage of Participants Who Meet the Markedly Abnormal Criteria for Safety Electrocardiogram (ECG) Parameters at Least Once Post Dose
Time frame: Baseline up to Day 11
Population: The safety analysis set included all participants who were enrolled and received study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TAK-935 300 mg Tablets Fed | Percentage of Participants Who Meet the Markedly Abnormal Criteria for Safety Electrocardiogram (ECG) Parameters at Least Once Post Dose | 33.3 percentage of participants |
| TAK-935 300 mg Tablets Fasted | Percentage of Participants Who Meet the Markedly Abnormal Criteria for Safety Electrocardiogram (ECG) Parameters at Least Once Post Dose | 33.3 percentage of participants |
| TAK-935 300 mg Solution Fasted | Percentage of Participants Who Meet the Markedly Abnormal Criteria for Safety Electrocardiogram (ECG) Parameters at Least Once Post Dose | 55.6 percentage of participants |
Secondary
Percentage of Participants Who Meet the Markedly Abnormal Criteria for Safety Laboratory Tests at Least Once Post Dose
Time frame: Baseline up to Day 11
Population: The safety analysis set included all participants who were enrolled and received study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TAK-935 300 mg Tablets Fed | Percentage of Participants Who Meet the Markedly Abnormal Criteria for Safety Laboratory Tests at Least Once Post Dose | 0 percentage of participants |
| TAK-935 300 mg Tablets Fasted | Percentage of Participants Who Meet the Markedly Abnormal Criteria for Safety Laboratory Tests at Least Once Post Dose | 0 percentage of participants |
| TAK-935 300 mg Solution Fasted | Percentage of Participants Who Meet the Markedly Abnormal Criteria for Safety Laboratory Tests at Least Once Post Dose | 0 percentage of participants |
Secondary
Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post Dose.
Time frame: Baseline up to Day 11
Population: The safety analysis set included all participants who were enrolled and received study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TAK-935 300 mg Tablets Fed | Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post Dose. | 22.2 percentage of participants |
| TAK-935 300 mg Tablets Fasted | Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post Dose. | 0 percentage of participants |
| TAK-935 300 mg Solution Fasted | Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post Dose. | 33.3 percentage of participants |