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| ID | Type | Description | Link |
|---|---|---|---|
| U1111-1164-7376 | Registry Identifier | WHO |
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The purpose of this study is to characterize the safety and tolerability profile of TAK-137 when administered as a single dose of tablets at escalating dose levels in healthy participants.
The drug being tested in this study is called TAK-137. TAK-137 is being tested to find a safe and well-tolerated dose. This study looked at safety (lab results and side effects) and pharmacokinetic properties (drug absorption, distribution, metabolism, and excretion) in people who took TAK-137. This study was designed as a single ascending 6 Cohort dose study with planned doses of 2, 5, 15, 50, and 100 mg and Cohort 6 dose to be determined if the maximum tolerated dose (MTD) was not reached. Anticipated enrollment was 48.
This study enrolled 47 participants and consisted of 6 Cohorts. Participants in Cohorts 1, 2, 3, 5 and 6 were randomized to receive a single dose of TAK-137 or placebo after a 10-hour fast. Participants in Cohort 4 were randomized to receive a single dose of TAK-137 or placebo under fasted conditions, followed by a single dose of TAK-137 or placebo under fed conditions 14 days later. Participants in cohort 4 will receive the same dose in both fasted and fed conditions. The starting dose was 2 mg followed by administrations of 5, 10, 0.5 and 20 mg.
This single-center trial was conducted in the United States. For Cohorts 1, 2, 3, 5, and 6 the overall time to participate in this study was up to 42 days. Participants made 4 visits to the clinic including one 5-day period of confinement to the clinic, and were contacted by telephone 14 days after last dose of study drug for a follow-up assessment.
For Cohort 4 the overall time to participate in this study was up to 56 days. Participants made 7 visits to the clinic including two 5-day periods of confinement to the clinic, and were contacted by telephone 14 days after last dose of study drug for a follow-up assessment.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Cohort 1: TAK-137 2 mg | Experimental | TAK-137 2 mg, tablets, orally, once on Day 1. |
|
| Cohort 2: TAK-137 5 mg | Experimental | TAK-137 5 mg, tablets, orally, once on Day 1. |
|
| Cohort 3: TAK-137 10 mg | Experimental | TAK-137 10 mg, tablets, orally, once on Day 1. |
|
| Cohort 4: TAK-137 5 mg Food Effect | Experimental | TAK-137 5 mg, tablets, orally, under fasted conditions, once on Day 1 of Period 1, followed by 14 days of follow-up, followed by TAK-137 5 mg, tablets, orally, under fed conditions, once on Day 1 of Period 2. |
|
| Cohort 5: TAK-137 0.5 mg | Experimental | TAK-137 0.5 mg, tablets, orally, once on Day 1. |
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| Cohort 6: TAK-137 20 mg | Experimental |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| TAK-137 | Drug | TAK-137 tablets |
|
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Participants Who Experienced at Least 1 Treatment-Emergent Adverse Event | 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 is defined as an adverse event with an onset that occurs after receiving study drug. | Day 1 to 14 days after the last dose of study medication(Up to 30 days) |
| Percentage of Participants With Abnormal Safety Laboratory Findings | The percentage of participants with any markedly abnormal standard safety laboratory values was collected throughout study. | Day 1 to 14 days after the last dose of study medication (Up to 30 Days) |
| Percentage of Participants With Markedly Abnormal Vital Sign Measurements | The percentage of participants with any markedly abnormal standard vital sign measurements was collected throughout study. | Day 1 to 14 days after the last dose of study medication |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | Day 1 |
| Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-137 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Medical Director Clinical Science | Takeda | Study Director |
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Healthy Volunteers were enrolled in a 6 Cohort randomized, dose escalating study at doses of 0.5, 2,5, 10 and 20 mg TAK-137 tablets or placebo single dose once in Cohorts 5,1,2,3 and 6 fasting respectively. Cohort 4 received 5 mg tablets or placebo single dose fasting then 5 mg or placebo fed.
Participants took part in the study at 1 investigative site in the United States from 21 June 2013 to 30 January 2014.
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| ID | Title | Description |
|---|---|---|
| FG000 | Cohort 1: TAK-137 2 mg | TAK-137 2 mg, tablets, orally, once on Day 1. |
| FG001 | Cohort 2: TAK-137 5 mg | TAK-137 5 mg, tablets, orally, once on Day 1. |
| FG002 | Cohort 3: TAK-137 10 mg | TAK-137 10 mg, tablets, orally, once on Day 1. |
| FG003 | Cohort 4: TAK-137 5 mg Food Effect | TAK-137 5 mg, tablets, orally, under fasted conditions, once on Day 1 of Period 1, followed by 14 days of follow-up, followed by TAK-137 5 mg, tablets, orally, under fed conditions, once on Day 1 of Period 2. |
| FG004 | Cohort 5: TAK-137 0.5 mg | TAK-137 0.5 mg, tablets, orally, once on Day 1. |
| FG005 | Cohort 6: TAK-137 20 mg | TAK-137 20 mg, tablets, orally, once on Day 1. |
| FG006 | Cohorts 1-6: Placebo | TAK-137 placebo-matching tablets, orally, once on Day 1. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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| ID | Title | Description |
|---|---|---|
| BG000 | Cohort 1: TAK-137 2 mg | TAK-137 2 mg, tablets, orally, once on Day 1. |
| BG001 | Cohort 2: TAK-137 5 mg | TAK-137 5 mg, tablets, orally, once on Day 1. |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Percentage of Participants Who Experienced at Least 1 Treatment-Emergent Adverse Event | 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 is defined as an adverse event with an onset that occurs after receiving study drug. | Safety population included all participants who received at least one dose of study medication. 8 of the 47 enrolled participants participated in Cohort 4 fed. | Posted | Number | percentage of participants | Day 1 to 14 days after the last dose of study medication(Up to 30 days) |
|
Day 1 to 14 days after the last dose of study medication (Up to 30 days).
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | TAK-137 0.5 mg | TAK-137 0.5 mg, tablets, orally, fasting, once on Day 1. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Nausea | Gastrointestinal disorders | MedDRA (16.1) | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Medical Director, Clinical Science | Takeda | +1-877-825-3327 | clinicaltrialregistry@tpna.com |
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| ID | Term |
|---|---|
| C000705611 | TAK-137 |
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TAK-137 20 mg, tablets, orally, once on Day 1.
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| Cohorts 1-6: Placebo | Placebo Comparator | TAK-137 placebo-matching tablets, orally, once on Day 1. |
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| Placebo | Drug | TAK-137 placebo-matching tablets |
|
Time to reach the maximum plasma concentration (Cmax), equal to time (hours) to Cmax. |
| Day 1 |
| AUC(0-tlqc): Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-137 | (AUC(0-tlqc) is a measure of total plasma exposure to the drug from Time 0 to Time of the Last Quantifiable Concentration (AUC[0-tlqc]). | Day 1 |
| AUC(0-inf): Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-137 | AUC(0-inf) is a measure of total plasma exposure to the drug from time zero extrapolated to infinity. | Day 1 |
| Terminal Elimination Half-life (T1/2) for TAK-137_101 | Terminal Phase Elimination Half-life (T1/2) is the time required for half of the drug to be eliminated from the plasma. | Day 1 |
| Apparent Clearance (CL/F) for TAK-137_101 | CL/F is apparent clearance of the drug from the plasma, calculated as the drug dose divided AUC(0-inf), expressed in liters per hour (L/hr). | Day 1 |
| Apparent Volume of Distribution (Vz/F) for TAK-137_101 | Vz/F is the distribution of a drug between plasma and the rest of the body following oral administration, calculated as CL/F divided by λz. | Day 1 |
| Total Amount of Drug (TAK-137) Excreted in Urine From Time 0 to Time t (Ae[0-t]) | Total amount of drug excreted in urine from time 0 to time t, calculated as Sum (Cu*Vu), where Cu is the concentration of drug excreted in urine and Vu is the volume of urine excreted. | Day 1 |
| Fraction of TAK-137 Excreted in Urine (Fe) | Fraction of drug excreted in urine, calculated as Fe=(Ae[0-t]/dose)×100. | Day 1 |
| Renal Clearance (CLr) for TAK-137 | CLr is a measure of apparent clearance of the drug from the urine, calculated as CLr=Ae(0-t)/AUC(0-96). | Day 1 |
| BG002 | Cohort 3: TAK-137 10 mg | TAK-137 10 mg, tablets, orally, once on Day 1. |
| BG003 | Cohort 4: TAK-137 5 mg Food Effect | TAK-137 5 mg, tablets, orally, under fasted conditions, once on Day 1 of Period 1, followed by 14 days of follow-up, followed by TAK-137 5 mg, tablets, orally, under fed conditions, once on Day 1 of Period 2. |
| BG004 | Cohort 5: TAK-137 0.5 mg | TAK-137 0.5 mg, tablets, orally, once on Day 1. |
| BG005 | Cohort 6: TAK-137 20 mg | TAK-137 20 mg, tablets, orally, once on Day 1. |
| BG006 | Cohorts 1-6: Placebo | TAK-137 placebo-matching tablets, orally, once on Day 1. |
| BG007 | Total | Total of all reporting groups |
| years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race/Ethnicity, Customized | Number | participants |
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| Race/Ethnicity, Customized | Number | participants |
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| Region of Enrollment | Number | participants |
|
| Height | Mean | Standard Deviation | cm |
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| Weight | Mean | Standard Deviation | kg |
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| Body Mass Index (BMI) | Mean | Standard Deviation | kg/m^2 |
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| Caffeine Consumption | Number | participants |
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| Smoking Classification | Number | participants |
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| Alcohol Classification | Number | participants |
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TAK-137 0.5 mg, tablets, orally, fasting, once on Day 1. |
| OG001 | TAK-137 2 mg | TAK-137 2 mg, tablets, orally, fasting, once on Day 1. |
| OG002 | TAK-137 5 mg (Fasting) | TAK-137 5 mg, tablets, orally, fasting, once on Day 1. |
| OG003 | TAK-137 10 mg | TAK-137 10 mg, tablets, orally, once on Day 1. |
| OG004 | TAK-137 20 mg | TAK-137 20 mg, tablets, orally, fasting, once on Day 1. |
| OG005 | TAK-137 Placebo | TAK-137 placebo-matching tablets, orally, once on Day 1. |
| OG006 | TAK-137 5 mg (Fed) | TAK-137 5 mg, tablets, orally, fed, once, on Day 1 of Period 2. |
| OG007 | Placebo (Fed) | TAK-137 placebo-matching tablets, orally, fed, once on Day 1of Period 2. |
|
|
| Primary | Percentage of Participants With Abnormal Safety Laboratory Findings | The percentage of participants with any markedly abnormal standard safety laboratory values was collected throughout study. | Participants from the Safety population, all participants who received at least one dose of study medication, with data available for analysis. 8 of the 47 enrolled participants participated in Cohort 4 fed. | Posted | Number | percentage of participants | Day 1 to 14 days after the last dose of study medication (Up to 30 Days) |
|
|
|
| Primary | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | The percentage of participants with any markedly abnormal standard vital sign measurements was collected throughout study. | Participants from the Safety population, all participants who received at least one dose of study medication, with data available for analysis. 8 of the 47 enrolled participants participated in Cohort 4 fed. | Posted | Number | percentage of participants | Day 1 to 14 days after the last dose of study medication |
|
|
|
| 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. | Participants from the Pharmacokinetic (PK) set, all participants who receive study drug and have at least one measureable concentration, with data available for analysis of this outcome measure. | Posted | Mean | Standard Deviation | ng/mL | Day 1 |
|
|
|
| Secondary | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-137 | Time to reach the maximum plasma concentration (Cmax), equal to time (hours) to Cmax. | Participants from the Pharmacokinetic (PK) set, all participants who receive study drug and have at least one measureable concentration, with data available for analysis of this outcome measure. | Posted | Median | Full Range | hours | Day 1 |
|
|
|
| Secondary | AUC(0-tlqc): Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-137 | (AUC(0-tlqc) is a measure of total plasma exposure to the drug from Time 0 to Time of the Last Quantifiable Concentration (AUC[0-tlqc]). | Participants from the Pharmacokinetic (PK) set, all participants who receive study drug and have at least one measureable concentration, with data available for analysis of this outcome measure. | Posted | Mean | Standard Deviation | ng*hr/mL | Day 1 |
|
|
|
| Secondary | AUC(0-inf): Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-137 | AUC(0-inf) is a measure of total plasma exposure to the drug from time zero extrapolated to infinity. | Participants from the Pharmacokinetic (PK) set, all participants who receive study drug and have at least one measureable concentration, with data available for analysis of this outcome measure. | Posted | Mean | Standard Deviation | ng*hr/mL | Day 1 |
|
|
|
| Secondary | Terminal Elimination Half-life (T1/2) for TAK-137_101 | Terminal Phase Elimination Half-life (T1/2) is the time required for half of the drug to be eliminated from the plasma. | Participants from the Pharmacokinetic (PK) set, all participants who receive study drug and have at least one measureable concentration, with data available for analysis of this outcome measure. | Posted | Mean | Standard Deviation | hours | Day 1 |
|
|
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| Secondary | Apparent Clearance (CL/F) for TAK-137_101 | CL/F is apparent clearance of the drug from the plasma, calculated as the drug dose divided AUC(0-inf), expressed in liters per hour (L/hr). | Participants from the Pharmacokinetic (PK) set, all participants who receive study drug and have at least one measureable concentration, with data available for analysis of this outcome measure. | Posted | Mean | Standard Deviation | liters/hour | Day 1 |
|
|
|
| Secondary | Apparent Volume of Distribution (Vz/F) for TAK-137_101 | Vz/F is the distribution of a drug between plasma and the rest of the body following oral administration, calculated as CL/F divided by λz. | Participants from the Pharmacokinetic (PK) set, all participants who receive study drug and have at least one measureable concentration, with data available for analysis of this outcome measure. | Posted | Mean | Standard Deviation | liters | Day 1 |
|
|
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| Secondary | Total Amount of Drug (TAK-137) Excreted in Urine From Time 0 to Time t (Ae[0-t]) | Total amount of drug excreted in urine from time 0 to time t, calculated as Sum (Cu*Vu), where Cu is the concentration of drug excreted in urine and Vu is the volume of urine excreted. | Participants from the Pharmacokinetic (PK) set, all participants who receive study drug and have at least one measureable concentration, with data available for analysis of this outcome measure. | Posted | Mean | Standard Deviation | mg | Day 1 |
|
|
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| Secondary | Fraction of TAK-137 Excreted in Urine (Fe) | Fraction of drug excreted in urine, calculated as Fe=(Ae[0-t]/dose)×100. | Participants from the Pharmacokinetic (PK) set, all participants who receive study drug and have at least one measureable concentration, with data available for analysis of this outcome measure. | Posted | Mean | Standard Deviation | percent excreted | Day 1 |
|
|
|
| Secondary | Renal Clearance (CLr) for TAK-137 | CLr is a measure of apparent clearance of the drug from the urine, calculated as CLr=Ae(0-t)/AUC(0-96). | Participants from the Pharmacokinetic (PK) set, all participants who receive study drug and have at least one measureable concentration, with data available for analysis of this outcome measure. | Posted | Mean | Standard Deviation | liters/hour | Day 1 |
|
|
|
| 0 |
| 6 |
| 0 |
| 6 |
| EG001 | TAK-137 2 mg | TAK-137 2 mg, tablets, orally, fasting, once on Day 1. | 0 | 6 | 1 | 6 |
| EG002 | TAK-137 5 mg (Fasting) | TAK-137 5 mg, tablets, orally, fasting, once on Day 1. | 0 | 11 | 0 | 11 |
| EG003 | TAK-137 10 mg | TAK-137 10 mg, tablets, orally, once on Day 1. | 0 | 6 | 1 | 6 |
| EG004 | TAK-137 20 mg | TAK-137 20 mg, tablets, orally, fasting, once on Day 1. | 0 | 6 | 3 | 6 |
| EG005 | Placebo Fasting | TAK-137 placebo-matching tablets, orally, fasting, once on Day 1. | 0 | 12 | 4 | 12 |
| EG006 | TAK-137 5 mg (Fed) | TAK-137 5 mg, tablets, orally, fed, once, on Day 1 of Period 2. | 0 | 6 | 1 | 6 |
| EG007 | Placebo (Fed) | TAK-137 placebo-matching tablets, orally, fed, once on Day 1of Period 2. | 0 | 2 | 0 | 2 |
| Diarrhoea | Gastrointestinal disorders | MedDRA (16.1) | Systematic Assessment |
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| Vomiting | Gastrointestinal disorders | MedDRA (16.1) | Systematic Assessment |
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| Upper respiratory tract infection | Infections and infestations | MedDRA (16.1) | Systematic Assessment |
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| Orthostatic heart rate response increased | Investigations | MedDRA (16.1) | Systematic Assessment |
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| Back pain | Musculoskeletal and connective tissue disorders | MedDRA (16.1) | Systematic Assessment |
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| Dizziness | Nervous system disorders | MedDRA (16.1) | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA (16.1) | Systematic Assessment |
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| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA (16.1) | Systematic Assessment |
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| Orthostatic hypotension | Vascular disorders | MedDRA (16.1) | Systematic Assessment |
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Research Organization shall not publish any articles or papers nor make any presentations, nor assist any other person in publishing any articles or papers or in making any presentations relating or referring to the Study or any results, data or insights from or any data, information or materials obtained or generated in the performance of its obligations without the prior written consent of Takeda, which consent may be granted or withheld in Takeda's sole discretion.
| Pulse (5 min after supine) >120 bpm |
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| Pulse (1 min after standing) <50 bpm |
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| Pulse (1 min after standing) >120 bpm |
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| Pulse (3 min after standing) <50 bpm |
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| Pulse (3 min after standing) >120 bpm |
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| Systolic BP (5 min after supine) <85 mmHG |
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| Systolic BP (5 min after supine) >180 mmHG |
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| Systolic BP (1 min after standing) <85 mmHG |
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| Systolic BP (1 min after standing) >180 mmHG |
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| Systolic BP (3 min after standing) <85 mmHG |
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| Systolic BP (3 min after standing) >180 mmHG |
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| Diastolic BP (5 min after supine) <50 mmHg |
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| Diastolic BP (5 min after supine) >110 mmHg |
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| Diastolic BP (1 min after standing) <50 mmHg |
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| Diastolic BP (1 min after standing) >110 mmHg |
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| Diastolic BP (3 min after standing) <50 mmHg |
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| Diastolic BP (3 min after standing) >110 mmHg |
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