Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Ascending Single- and Multiple-Doses of TAK-020 in Healthy Volunteers
- Conditions
- Healthy Volunteers
- Interventions
- Drug: TAK-020 PlaceboDrug: TAK-020
- Registration Number
- NCT02413255
- Lead Sponsor
- Takeda
- Brief Summary
The purpose of this study is to evaluate the safety, tolerability, and pharmacokinetics of ascending single- and multiple-doses of TAK-020 in healthy participants.
- Detailed Description
The drug being tested in this study is called TAK-020. TAK-020 is being tested to evaluate safety and tolerability of single doses and 7 days multiple doses of TAK-020 in healthy volunteers. This study will look at the PK characteristics (how the drug acts throughout the body) of the drug and safety and tolerability (lab results, vital signs, ECG, and side effects) in healthy participants who take TAK-020.
The study will enroll a total of approximately 120 participants. This study is designed to consist of 2 sequential parts: Part 1-a SRD, and Part 2-a MRD. Healthy participants for Part 1 will be enrolled into 9 cohorts. Each cohort will have 8 randomized participants with receiving a single dose of TAK-020, and 2 receiving matching placebo under fasted conditions. In Cohorts 1-9 doses of 0.1, 0.5, 2.5, 4.4, 8.8, 17.5, 35, 70 and 105 mg will be evaluated.
Healthy participants for Part 2 will be enrolled into 7 cohorts. Each cohort will have 8 randomized participants, with participants receiving one dose of TAK-020 on Day 1, followed by a washout on Day 2, then daily dosing on Days 3-9 of TAK-020 with 2 participants receiving matching placebo under fasted conditions. In Cohorts 1-4 doses of 3.75, 5.75, 13 and 25 mg will be evaluated. For Cohorts 5-7, the subsequent dose level is to be determined based on data from Part 1 and review of safety, tolerability and PK data from Part 2 Cohorts 1-4.
This single-center trial will be conducted in the United States. The overall time to participate in this study is up to 45 days. Participants in Part 1 will make multiple visits to the clinic including a period of confinement to the clinic and will be contacted by telephone 14 days after the last dose of study drug for a follow-up assessment. Participants in Part 2 will make multiple visits to the clinic including a period of confinement to the clinic and will be observed at the clinic 17 days after the last dose of study drug for a follow-up assessment.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 120
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Part 1 Cohort 1-9: Placebo TAK-020 Placebo TAK-020 placebo-matching solution, orally, once on Day 1. Part 1 Cohort 1: TAK-020 0.1 mg TAK-020 TAK-020 0.1 mg, solution, orally once on Day 1. Part 1 Cohort 2: TAK-020 0.5 mg TAK-020 TAK-020 0.5 mg, solution, orally, once on Day 1 following review of safety, tolerability and pharmacokinetic (PK) data from Cohort 1. Part 1 Cohort 3: TAK-020 2.5 mg TAK-020 TAK-020 2.5 mg, solution, orally once on Day 1 following review of safety, tolerability and PK data from Cohort 2. Part 1 Cohort 4: TAK-020 4.4 mg TAK-020 TAK-020 4.4 mg, solution, orally once on Day 1 following review of safety, tolerability and PK data from Cohort 3. Part 1 Cohort 5: TAK-020 8.8 mg TAK-020 TAK-020 8.8 mg, solution, orally once on Day 1 following review of safety, tolerability and PK data from Cohort 4. Part 1 Cohort 6: TAK-020 17.5 mg TAK-020 TAK-020 17.5 mg, solution, orally once on Day 1 following review of safety, tolerability and PK data from Cohort 5. Part 1 Cohort 7: TAK-020 35 mg TAK-020 TAK-020 35 mg, solution, orally once on Day 1. TAK-020 dose will be determined based on review of safety, tolerability and PK data from Cohort 6. Part 1 Cohort 8: TAK-020 70 mg TAK-020 TAK-020 70 mg, solution, orally once on Day 1. TAK-020 dose will be determined based on review of safety, tolerability and PK data from Cohort 7. Part 1 Cohort 9: TAK-020 105 mg TAK-020 TAK-020 105 mg, solution, orally once on Day 1. TAK-020 dose will be determined based on review of safety, tolerability and PK data from Cohort 8. Part 2 Cohort 1-6: Placebo TAK-020 Placebo TAK-020 placebo-matching solution, orally, once on Day 1 and Days 3 to 9. Part 2 Cohort 1: TAK-020 3.75 mg TAK-020 TAK-020 3.75 mg, solution, orally once on Day 1 and Days 3-9. TAK-020 dose are determined based on data from Part 1 of the study. Part 2 Cohort 2: TAK-020 5.75 mg TAK-020 TAK-020 5.75 mg, solution, orally once on Day 1 and Days 3-9. TAK-020 dose will be determined based on data from Part 1 and review of safety, tolerability and PK data from Cohort 1 in Part 2. Part 2 Cohort 3: TAK-020 13 mg TAK-020 TAK-020 13 mg, solution, orally once on Day 1 and Days 3-9. TAK-020 dose will be determined based on data from Part 1 and review of safety, tolerability and PK data from Cohort 2 in Part 2. Part 2 Cohort 4: TAK-020 25 mg TAK-020 TAK-020 25 mg, solution, orally once on Day 1 and Days 3-9. TAK-020 dose will be determined based on data from Part 1 and review of safety, tolerability and PK data from Cohort 3 in Part 2. Part 2 Cohort 5: TAK-020 45 mg TAK-020 TAK-020 45 mg, solution, orally once on Day 1 and Days 3-9. TAK-020 dose was determined based on data from Part 1 and review of safety, tolerability and PK data from Cohort 4 in Part 2. Part 2 Cohort 6: TAK-020 60 mg TAK-020 TAK-020 60 mg, solution, orally once on Day 1 and Days 3-9. TAK-020 dose was determined based on data from Part 1 and review of safety, tolerability and PK data from Cohort 5 in Part 2.
- Primary Outcome Measures
Name Time Method Percentage of Participants Who Experience at Least One Treatment-emergent Adverse Event (TEAE) in Part 2 Multiple-rising Dose (MRD) First dose of study drug up to and including 30 days after last dose of study drug (Up to 39 days) in Part 2 An 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. A TEAE is defined as an adverse event that occurred or worsened after receiving study drug.
Percentage of Participants With MAV for Safety Laboratory Findings at Least Once Post-dose in Part 2 (MRD) From Day 1 to Day 17 in Part 2 Safety laboratory tests include hematology, and serum chemistries.
Percentage of Participants Who Experience at Least One Treatment-emergent Adverse Event (TEAE) in Part 1 Single-rising Dose (SRD) First dose of study drug up to and including 30 days after last dose of study drug (Up to 31 days) for Part 1 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. A TEAE is defined as an adverse event that occurred or worsened after receiving study drug.
Percentage of Participants With MAV for Safety Electrocardiogram (ECG) Parameters at Least Once Post-dose in Part 1 (SRD) From Day 1 to Day 14 in Part 1 A standard 12-lead ECG was performed. Change from baseline=CFB.
Percentage of Participants With MAV for Vital Sign Measurements at Least Once Post-dose in Part 2 (MRD) From Day 1 to Day 17 in Part 2 Vital signs include oral temperature respiratory rate, sitting blood pressure (after 5 minutes resting) and pulse (bpm).
Percentage of Participants With Markedly Abnormal Values (MAV) for Safety Laboratory Findings at Least Once Post-dose in Part 1 (SRD) From Day 1 to Day 14 of Part 1 Safety laboratory tests includes hematology, serum chemistries, and urinalysis.
Percentage of Participants With MAV for Vital Sign Measurements at Least Once Post-dose in Part 1 (SRD) From Day 1 to Day 14 of Part 1 Vital signs include oral temperature, respiratory rate, sitting blood pressure (after 5 minutes resting) and pulse beats per minute (bpm).
Percentage of Participants With MAV for Safety ECG Parameters at Least Once Post-dose in Part 2 (MRD) From Day 1 to Day 17 in Part 2 A standard 12-lead ECG was performed.
- Secondary Outcome Measures
Name Time Method Cmax/D: Maximum Observed Plasma Concentration Divided by TAK-020 Dose for TAK-020 (SRD) Pre-dose and multiple timepoints (up to 96 hours) post-dose in Part 1 Cmax: Maximum Observed Plasma Concentration for TAK-020 in Part 1 (SRD) Pre-dose and multiple timepoints (up to 96 hours) post-dose in Part 1 Cmax: Maximum Observed Plasma Concentration for TAK-020 in Part 2 (MRD) Pre-dose and multiple timepoints (up to 48 hours) post-dose on Day 1 and pre-dose and multiple timepoints (up to 24 hours) post-dose on Day 9 in Part 2 Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-020 in Part 1 (SRD) Pre-dose and multiple timepoints (up to 96 hours) post-dose in Part 1 Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-020 in Part 2 (MRD) Pre-dose and multiple timepoints (up to 48 hours) post-dose on Day 1 and pre-dose and multiple time-points (up to 24 hours) post dose on Day 9 in Part 2 AUC24: Area Under the Plasma Concentration-time Curve From Time 0 to Time 24 Hours for TAK-020 in Part 1 (SRD) Pre-dose and multiple timepoints (up to 24 hours) post-dose in Part 1 AUCt: Area Under the Plasma Concentration-time Curve From Time 0 to Time t Over the Dosing Interval for TAK-020 (SRD) Pre-dose and multiple timepoints (up to 96 hours) post-dose in Part 1 AUCt: Area Under the Plasma Concentration-time Curve From Time 0 to Time t Over the Dosing Interval for TAK-020 in Part 2 (MRD) Pre-dose and multiple timepoints (up to 48 hours) post-dose on Day 1 and pre-dose and multiple timepoints (up to 24 hours) post-dose on Day 9 in Part 2 CL/F: Apparent Clearance After Extravascular Administration Calculated Using the Observed Value of the Last Quantifiable Concentration of TAK-020 in Part 1 (SRD) Pre-dose and multiple timepoints (up to 96 hours) post-dose in Part 1 CL/F was calculated as dose/AUC∞.
AUC24/D: Area Under the Plasma Concentration-time Curve From Time 0 to Time 24 Hours Divided by TAK-020 Dose for TAK-020 in Part 2 (MRD) Pre-dose and multiple timepoints (up to 24 Hours) post-dose on Day 1 and pre-dose and multiple timepoints (up to 24 hours) post-dose on Day 9 in Part 2 AUC24: Area Under the Plasma Concentration-time Curve From Time 0 to Time 24 Hours for TAK-020 in Part 2 (MRD) Pre-dose and multiple timepoints (up to 24 hours) post-dose on Day 1 and pre-dose and multiple timepoints (up to 24 hours) post dose on Day 9 in Part 2 AUC24/D: Area Under the Plasma Concentration-time Curve From Time 0 to Time 24 Hours Divided by TAK-020 Dose for TAK-020 in Part 1 (SRD) Pre-dose and multiple timepoints (up to 24 hours) post-dose in Part 1 AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity Calculated Using the Observed Value for the Last Quantifiable Concentration for TAK-020 in Part 1 (SRD) Pre-dose and multiple timepoints (up to 96 hours) post-dose in Part 1 Rac(Cmax): Accumulation Ratio Based on Cmax Calculated as Cmax at Steady State/Cmax After a Single Dose for TAK-020 (MRD) Pre-dose and multiple timepoints (up to 24 hours) post-dose on Day 9 in Part 2 Cmax/D: Maximum Observed Plasma Concentration Divided by TAK-020 Dose for TAK-020 (MRD) Pre-dose and multiple timepoints (up to 48 hours) post-dose on Day 1 and pre-dose and multiple timepoints (up to 24 hours) post-dose on Day 9 in Part 2 Terminal Disposition Phase Half-life for TAK-020 in Part 1 (SRD) Pre-dose and multiple timepoints (up to 96 hours) post-dose in Part 1 T1/2z : Terminal Disposition Phase Half-life (T1/2z) for TAK-020 in Part 2 (MRD) Pre-dose and multiple timepoints (up to 48 hours) post-dose on Day 1 and pre-dose and multiple timepoints (up to 24 hours) post-dose on Day 9 in Part 2 Lambda z (Λz): Terminal Disposition Phase Rate Constant for TAK-020 (SRD) Pre-dose and multiple timepoints (up to 96 hours) post-dose in Part 1 AUC∞:Area Under the Plasma Concentration-time Curve From Time 0 to Infinity Calculated Using the Observed Value for the Last Quantifiable Concentration for TAK-020 in Part 2 (MRD) Pre-dose and multiple timepoints (up to 48 hours) post-dose on Day 1 in Part 2 Rac(AUC): Accumulation Ratio Based on AUC Calculated as AUC24 at Steady State/AUC24 After a Single Dose for TAK-020 (MRD) Pre-dose and multiple timepoints (up to 24 hours) post-dose on Day 9 in Part 2 Tlag: Lag Time to First Quantifiable Concentration for TAK-020 (MRD) Pre-dose and multiple timepoints (up to 48 hours) post-dose on Day 1 and pre-dose and multiple timepoints (up to 24 hours) post-dose on Day 9 in Part 2 Apparent Volume of Distribution (Vz/F) During the Terminal Disposition Phase After Extravascular Administration Calculated Using the Observed Value for the Last Quantifiable Concentration for TAK-020 in Part 1 (SRD) Pre-dose and multiple timepoints (up to 96 hours) post-dose in Part 1 Vz/F was calculated as (CL/F)/λz.
Ae(0-24) : Amount of Drug Excreted in Urine During a 24-hour Dosing Interval for TAK-020 in Part 1 (SRD) Pre-dose and multiple timepoints (up to 24 hours) post-dose in Part 1 Ae(0-24) was calculated as calculated as Cur\*Vur, where Cur was the concentration of drug excreted in urine and Vur is the volume of urine excreted.
Renal Clearance (CLr) for TAK-020 in Part 2 (MRD) Pre-dose and multiple timepoints (up to 48 hours) post-dose on Day 1 and pre-dose and multiple timepoints (up to 24 hours) post-dose on Day 9 in Part 2 CLr was calculated as (Ae24/AUC24)\*100.
Lamda z (Λz):Terminal Disposition Phase Rate Constant for TAK-020 (MRD) From pre-dose to 96 hours post-dose in Part 1 and pre-dose and multiple timepoints (up to 24 hours) post-dose on Day 9 in Part 2 Tlag: Lag Time to First Quantifiable Concentration for TAK-020 (SRD) Pre-dose and multiple timepoints (up to 96 hours) post-dose in Part 1 Fe(0-24): Fraction of Drug Excreted in Urine for TAK-020 in Part 2 (MRD) Pre-dose and multiple timepoints (up to 24 hours) post-dose on Day 1 and Day 9 in Part 2 Fe was calculated as (Aet/dose)\*100.
CL/F: Apparent Clearance After Extravascular Administration Calculated Using the Observed Value of the Last Quantifiable Concentration of TAK-020 in Part 2 (MRD) Pre-dose and multiple timepoints (up to 48 hours) post-dose on Day 1 and pre-dose and multiple timepoints (up to 24 hours) post-dose on Day 9 in Part 2 CL/F was calculated as dose/AUCτ.
Apparent Volume of Distribution (Vz/F) During the Terminal Disposition Phase After Extravascular Administration Calculated Using the Observed Value for the Last Quantifiable Concentration for TAK-020 in Part 2 (MRD) Pre-dose and multiple timepoints (up to 48 hours) post-dose on Day 1 and pre-dose and multiple timepoints (up to 24 hours) post-dose on Day 9 in Part 2 Vz/F was calculated as (CL/F)/λz.
Ae(0-24): Amount of Drug Excreted in Urine During a 24-hour Dosing Interval for TAK-020 in Part 2 (MRD) Pre-dose and multiple timepoints (up to 24 hours) post-dose on Day 1 and Day 9 in Part 2 Ae(0-24) is calculated as calculated as Cur\*Vur, where Cu was the concentration of drug excreted in urine and Vur is the volume of urine excreted.
Ae(0-96): Amount of Drug Excreted in Urine From Time 0 to Time 96 Hours for TAK-020 in Part 1 (SRD) Pre-dose and multiple timepoints (up to 96 hours) post-dose in Part 1 Fe(0-24): Fraction of Drug Excreted in Urine for TAK-020 in Part 1 (SRD) Pre-dose and multiple timepoints (up to 24 hours) post-dose in Part 1 Fe was calculated as (Aet/dose)\*100.
Renal Clearance (CLr) for TAK-020 in Part 1 (SRD) Pre-dose and multiple timepoints (up to 96 hours) post-dose in Part 1 CLr was calculated as (Ae96/AUCt)\*100.
R: Linearity Index Calculated as AUC24 at Steady State/AUC∞ After a Single Dose for TAK-020 in Part 2 (MRD) Pre-dose and multiple timepoints (Up to 48 hours) post-dose on Day 1 and pre-dose and multiple timepoints (up to 24 hours) post-dose on Day 9 in Part 2 Fe(0-96): Fraction of Drug Excreted in Urine for TAK-020 in Part 1 (SRD) Pre-dose and multiple timepoints (up to 96 hours) post-dose in Part 1 Fe was calculated as (Aet/dose)\*100.