Phase 1
N=120
Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Ascending Single- and Multiple-Doses of TAK-020 in Healthy Volunteers
Healthy Volunteers
Bottom Line
View on ClinicalTrials.gov: NCT02413255 ↗Enrolled (actual)
120
Serious AEs
0.0%
Results posted
Jan 2019
Primary outcome: Primary: Percentage of Participants Who Experience at Least One Treatment-emergent Adverse Event (TEAE) in Part 1 Single-rising Dose (SRD) — 11.1; 0; 0; 16.7 percentage of participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 1
- Interventions
- TAK-020 (Drug); TAK-020 Placebo (Drug)
- Age
- Adult · 18+ yrs
- Sex
- All
- Sponsor
- Takeda
- Primary completion
- May 2017
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Percentage of Participants Who Experience at Least One Treatment-emergent Adverse Event (TEAE) in Part 1 Single-rising Dose (SRD) |
11.1; 0; 0; 16.7; 0; 16.7 | — |
| PRIMARY Percentage of Participants With Markedly Abnormal Values (MAV) for Safety Laboratory Findings at Least Once Post-dose in Part 1 (SRD) |
0; 0; 0; 0; 0; 0 | — |
| PRIMARY Percentage of Participants With MAV for Vital Sign Measurements at Least Once Post-dose in Part 1 (SRD) |
11.1; 0; 16.7; 16.7; 16.7; 0 | — |
| PRIMARY Percentage of Participants With MAV for Safety Electrocardiogram (ECG) Parameters at Least Once Post-dose in Part 1 (SRD) |
44.4; 16.7; 16.7; 50.0; 16.7; 16.7 | — |
| PRIMARY Percentage of Participants Who Experience at Least One Treatment-emergent Adverse Event (TEAE) in Part 2 Multiple-rising Dose (MRD) |
41.7; 16.7; 50.0; 50.0; 33.3; 16.7 | — |
| PRIMARY Percentage of Participants With MAV for Safety Laboratory Findings at Least Once Post-dose in Part 2 (MRD) |
0; 0; 0; 0; 0; 0 | — |
| PRIMARY Percentage of Participants With MAV for Vital Sign Measurements at Least Once Post-dose in Part 2 (MRD) |
8.3; 0; 16.7; 0; 16.7; 0 | — |
| PRIMARY Percentage of Participants With MAV for Safety ECG Parameters at Least Once Post-dose in Part 2 (MRD) |
16.7; 16.7; 16.7; 50.0; 50.0; 16.7 | — |
| SECONDARY Cmax: Maximum Observed Plasma Concentration for TAK-020 in Part 1 (SRD) |
0.4631; 1.5529; 13.5475; 24.2013; 42.8329; 105.7708 | 0.465 |
| SECONDARY Cmax: Maximum Observed Plasma Concentration for TAK-020 in Part 2 (MRD) |
16.4167; 40.3204; 64.7590; 161.9015; 300.8684; 423.8189 | 0.126 |
| SECONDARY Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-020 in Part 1 (SRD) |
0.750; 0.700; 0.745; 0.825; 0.780; 1.010 | 0.5402 |
| SECONDARY Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-020 in Part 2 (MRD) |
0.750; 0.750; 0.750; 0.750; 0.500; 0.640 | 0.7824 |
| SECONDARY AUC24: Area Under the Plasma Concentration-time Curve From Time 0 to Time 24 Hours for TAK-020 in Part 1 (SRD) |
0.7599; 3.6691; 29.7502; 63.1772; 98.8228; 272.3381 | 0.019 sig |
| SECONDARY AUC24: Area Under the Plasma Concentration-time Curve From Time 0 to Time 24 Hours for TAK-020 in Part 2 (MRD) |
34.6177; 86.4177; 148.6319; 389.8000; 576.1987; 808.3223 | 0.258 |
| SECONDARY 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) |
7.5994; 7.3382; 11.9001; 14.3584; 11.2299; 15.5622 | — |
| SECONDARY 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) |
9.2314; 15.0292; 11.4332; 15.5920; 12.8044; 13.4720 | — |
| SECONDARY AUCt: Area Under the Plasma Concentration-time Curve From Time 0 to Time t Over the Dosing Interval for TAK-020 (SRD) |
0.6674; 3.5250; 29.4206; 62.4593; 98.6610; 273.0083 | 0.003 sig |
| SECONDARY 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) |
34.1425; 85.7708; 148.6319; 391.5478; 583.7178; 823.3525 | 0.201 |
| SECONDARY 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) |
1.3733; 3.8341; 29.9808; 69.3298; 100.2928; 275.1708 | 0.490 |
| SECONDARY 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) |
34.8469; 86.7892; 149.9419; 393.8737; 587.4204; 825.6238 | 0.224 |
| SECONDARY Rac(AUC): Accumulation Ratio Based on AUC Calculated as AUC24 at Steady State/AUC24 After a Single Dose for TAK-020 (MRD) |
1.1285; 1.1606; 0.9903; 1.0628; 1.1263; 1.2511 | — |
| SECONDARY Rac(Cmax): Accumulation Ratio Based on Cmax Calculated as Cmax at Steady State/Cmax After a Single Dose for TAK-020 (MRD) |
1.0780; 0.9830; 0.9831; 0.9379; 0.9294; 1.0227 | — |
| SECONDARY Cmax/D: Maximum Observed Plasma Concentration Divided by TAK-020 Dose for TAK-020 (SRD) |
4.6312; 3.1058; 5.4190; 5.5003; 4.8674; 6.0440 | — |
| SECONDARY Cmax/D: Maximum Observed Plasma Concentration Divided by TAK-020 Dose for TAK-020 (MRD) |
4.3778; 7.0123; 4.9815; 6.4761; 6.6860; 7.0636 | — |
| SECONDARY Terminal Disposition Phase Half-life for TAK-020 in Part 1 (SRD) |
1.1251; 1.5323; 2.2093; 3.0159; 4.8384; 4.2946 | — |
| SECONDARY T1/2z : Terminal Disposition Phase Half-life (T1/2z) for TAK-020 in Part 2 (MRD) |
2.5948; 3.3397; 4.1895; 4.8507; 6.0124; 6.2971 | — |
| SECONDARY Lambda z (Λz): Terminal Disposition Phase Rate Constant for TAK-020 (SRD) |
0.6226; 0.4659; 0.3223; 0.2402; 0.1496; 0.1745 | <.0001 sig |
| SECONDARY Lamda z (Λz):Terminal Disposition Phase Rate Constant for TAK-020 (MRD) |
0.2732; 0.2231; 0.1667; 0.1655; 0.1263; 0.1216 | — |
| SECONDARY Tlag: Lag Time to First Quantifiable Concentration for TAK-020 (SRD) |
0.0000; 0.0000; 0.0000; 0.0000; 0.0000; 0.0000 | — |
| SECONDARY Tlag: Lag Time to First Quantifiable Concentration for TAK-020 (MRD) |
0.0000; 0.0000; 0.0000; 0.0000; 0.0000; 0.0000 | — |
| SECONDARY CL/F: Apparent Clearance After Extravascular Administration Calculated Using the Observed Value of the Last Quantifiable Concentration of TAK-020 in Part 1 (SRD) |
74.6058; 134.3327; 90.8722; 64.9449; 92.1842; 67.4975 | — |
| SECONDARY CL/F: Apparent Clearance After Extravascular Administration Calculated Using the Observed Value of the Last Quantifiable Concentration of TAK-020 in Part 2 (MRD) |
118.3171; 67.1355; 100.6915; 68.2909; 79.5377; 76.9650 | — |
| SECONDARY 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) |
118.3923; 292.2714; 290.5190; 281.7423; 655.4794; 416.8746 | — |
| SECONDARY 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) |
442.5900; 329.6057; 632.4288; 460.7824; 698.3679; 715.0788 | — |
| SECONDARY Ae(0-24) : Amount of Drug Excreted in Urine During a 24-hour Dosing Interval for TAK-020 in Part 1 (SRD) |
0.002473; 0.009898; 0.069183; 0.128195; 0.227985; 0.507260 | — |
| SECONDARY Ae(0-24): Amount of Drug Excreted in Urine During a 24-hour Dosing Interval for TAK-020 in Part 2 (MRD) |
0.086153; 0.149595; 0.418761; 1.095832; 1.186754; 1.569498 | — |
| SECONDARY Ae(0-96): Amount of Drug Excreted in Urine From Time 0 to Time 96 Hours for TAK-020 in Part 1 (SRD) |
0.002473; 0.009999; 0.069676; 0.128604; 0.229946; 0.514036 | — |
| SECONDARY Fe(0-24): Fraction of Drug Excreted in Urine for TAK-020 in Part 1 (SRD) |
2.4733; 1.9796; 2.7673; 2.9135; 2.5907; 2.8986 | — |
| SECONDARY Fe(0-24): Fraction of Drug Excreted in Urine for TAK-020 in Part 2 (MRD) |
2.2974; 2.6016; 3.2212; 4.3833; 2.6372; 2.6158 | — |
| SECONDARY Fe(0-96): Fraction of Drug Excreted in Urine for TAK-020 in Part 1 (SRD) |
2.4733; 1.9999; 2.7870; 2.9228; 2.6130; 2.9373 | — |
| SECONDARY Renal Clearance (CLr) for TAK-020 in Part 1 (SRD) |
3.6856; 2.6010; 2.5250; 2.0190; 2.2159; 1.8896 | — |
| SECONDARY Renal Clearance (CLr) for TAK-020 in Part 2 (MRD) |
2.3165; 1.7168; 2.8969; 2.6497; 2.1525; 1.9597 | — |
| SECONDARY R: Linearity Index Calculated as AUC24 at Steady State/AUC∞ After a Single Dose for TAK-020 in Part 2 (MRD) |
3.551; 4.463; 5.010; 5.940; 6.376; 6.716 | — |
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.
Eligibility Criteria
Inclusion Criteria
Participant eligibility is determined according to the following criteria prior to entry into the study:
- In the opinion of the investigator, the participant is capable of understanding and complying with protocol requirements.
- Participant or, when applicable, the participant's legally acceptable representative signs and dates a written, informed consent form and any required privacy authorization prior to the initiation of any study procedures including requesting that a participant fast for any laboratory evaluations.
- Participant is a healthy adult male or female.
- The participant is a health adult male or female aged 18 to 55 years, inclusive, at the time of informed consent and first study medication dose.
- The participant weighs at least 45 kilogram (kg) and has a body mass index (BMI) between 18.0 and 32.0 kilogram per square meter (kg/m^2), inclusive at Screening and Day -1.
- A male participant who is nonsterilized and sexually active with a female partner of childbearing potential agrees to use adequate contraception from signing of informed consent throughout the duration of the study and for 12 weeks after last dose.
- A female participant of childbearing potential who is sexually active with a nonsterilized male partner agrees to use adequate contraception from signing of informed consent throughout the duration of the study and until the next menstrual period or 30 days after last dose, whichever is first. If the next menstrual period is delayed, a pregnancy test will be required for exclusion of pregnancy.
Exclusion Criteria
Any participant who meets any of the following criteria will not qualify for entry into the study:
- The participant has received any investigational compound within 30 days prior to Screening.
- The participant is an immediate family member, study site employee, or in a dependent relationship with a study site employee who is involved in the conduct of this study (example, spouse, parent, child, sibling) or may consent under duress.
- Participant has a known hypersensitivity to any component of the formulation of TAK-020, Captisol or related compounds.
- The participant has a positive urine drug result for drugs of abuse at Screening or Check-in (Day -1).
- The participant has a history of drug abuse (defined as any illicit drug use) or a history of alcohol abuse (defined as 4 or more alcoholic beverages per day) within 1 year 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 1 measure of spirits or 1 glass of wine.
- Participant has taken any excluded medication, supplements, or food products, Prohibited Medications and Dietary Products.
- If female, the participant is pregnant or lactating or intending to become pregnant before, during or within 1 month after exit from this study (30 days post last dose); or intending to donate ova during such time period.
- If male, the participant intends to donate sperm during the course of this study or for 12 weeks thereafter.
- Participant has evidence of current cardiovascular, central nervous system, hepatic, hematopoietic disease, renal dysfunction, metabolic or endocrine dysfunction, serious allergy, asthma hypoxemia, hypertension, seizures, or allergic skin rash. There is any finding in the participant's medical history, physical examination, or safety laboratory tests giving reasonable suspicion of a disease that would contraindicate taking TAK-020, or a similar drug in the same class, or that might interfere with the conduct of the study. This includes, but is not limited to, peptic ulcer disease, seizure disorders, and cardiac arrhythmias.
- Participant has current or recent (within 6 months) gastrointestinal disease that would be expected to influence the absorption of drugs (that is, a history of malabsorption, esophageal reflux, peptic ulcer disease, erosive esophagitis frequent [more
Data sourced from ClinicalTrials.gov (NCT02413255). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.