Phase 1
Completed N=88
Phase 1, TAK-915-1001, Single-Rising Dose, Multiple-Rising Dose, Drug-Drug Interaction, Relative Bioavailability, Food Effect, and Effect on Elderly Participants Study
Healthy Volunteers
Source: ClinicalTrials.gov NCT02461160 ↗
Enrolled (actual)
88
Serious AEs
0.7%
Results posted
Feb 2019
Primary outcomePrimary: Percentage of Participants Who Experience at Least One Treatment Emergent Adverse Event (TEAE) — 0; 16.7; 33.3; 16.7 percentage of participants
Summary
The purpose of this study is to characterize the safety, tolerability and plasma pharmacokinetic (PK) profile of TAK-915 when administered as single and multiple oral suspension doses at escalating dose levels in healthy participants, including elderly participants.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Percentage of Participants Who Experience at Least One Treatment Emergent Adverse Event (TEAE) |
0; 16.7; 33.3; 16.7; 16.7; 33.3 | — |
| PRIMARY Percentage of Participants With Markedly Abnormal Safety Laboratory Tests |
0; 0; 0; 0; 0; 0 | — |
| PRIMARY Percentage of Participants With Markedly Abnormal Vital Sign Measurements |
0; 0; 0; 0; 0; 0 | — |
| PRIMARY Percentage of Participants With Markedly Abnormal Values of 12-Lead Electrocardiogram (ECG) Parameters |
37.5; 0; 16.7; 25; 66.7; 50 | — |
| PRIMARY Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-915 |
1.750; 2.000; 2.000; 2.508; 1.500; 1.500 | — |
| PRIMARY Cmax: Maximum Observed Plasma Concentration for TAK-915 |
203.7; 654.8; 417.3; 675.8; 209.5; 651.8 | — |
| PRIMARY AUC(0-24): Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours Postdose for TAK-915 |
2560.0; 8293.3; 5478.1; 10285.1; 2610.0; 7984.6 | — |
| PRIMARY AUClast: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-915 |
5187.3; 18229.5; 10812.4; 24204.7; 5380.9; 15640.0 | — |
| PRIMARY AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-915 |
6197.1; 19345.6; 12198.3; 30243.3; 6565.6; 17507.2 | — |
| PRIMARY Rac(AUC): Accumulation Ratios Between Day 14 AUC(0-24) and Day 1 AUC(0-24) for TAK-915 |
2.100; 1.973; 2.761 | — |
| PRIMARY Rac(Cmax): Accumulation Ratios Between Day 14 Cmax and Day 1 Cmax for TAK-915 |
1.884; 1.859; 2.556 | — |
| PRIMARY Time Dependency Assessment From AUC(0-24) After Last Dose for TAK-915 on Day 14 in MRD Cohorts Compared to AUC(0-inf) After a Single Dose on Day 1 |
0.873; 0.883; 0.846 | — |
| PRIMARY Cmax: Maximum Observed Plasma Concentration for Midazolam Alone (Day 1) and in the Presence of TAK-915 (Day 16) in DDI Cohort |
9.6; 8.3 | — |
| PRIMARY AUC(0-24): Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours Postdose for Midazolam Alone (Day 1) and in the Presence of TAK-915 (Day 16) in DDI Cohort |
25.0; 17.4 | — |
| PRIMARY AUC(0-24) for Midazolam After Single Dose (Day 1)/AUC(0-24) for Midazolam After 7 Daily Doses of TAK-915 (Day 16) in DDI Cohort |
0.735 | — |
| SECONDARY Terminal Elimination Half-life (t1/2) for TAK-915 |
35.246; 34.008; 32.621; 37.826; 37.166; 23.326 | — |
| SECONDARY CL/F: Apparent Clearance for TAK-915 |
4.966; 5.565; 16.566; 6.928; 5.437; 5.993 | — |
| SECONDARY Apparent Volume of Distribution (Vz/F) for TAK-915 |
271.621; 253.274; 739.900; 384.373; 253.191; 219.807 | — |
| SECONDARY Total Amount of Drug Excreted in Urine (Ae) for TAK-915 |
10716.238; 56307.372; 39016.323; 70789.157; 11637.538; 75873.405 | — |
| SECONDARY Fraction of Drug Excreted in Urine (Fe) for TAK-915 |
0.036; 0.056; 0.020; 0.035; 0.039; 0.076 | — |
| SECONDARY Renal Clearance (CLr) for TAK-915 |
2.140; 3.191; 3.612; 2.915; 2.265; 5.047 | — |
| SECONDARY Cmax: Maximum Observed Plasma Concentration for TAK-915 on Day 1 in DDI Cohort |
519.7 | — |
| SECONDARY AUC(0-24): Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours Postdose for TAK-915 on Day 1 in DDI Cohort |
7324.5 | — |
| SECONDARY AUC(0-tau): Area Under the Plasma Concentration-Time Curve From Time 0 to Time Tau Over a Dosing Interval Where Tau is the Length of the Dosing Interval for TAK-915 in DDI Cohort |
17093.9 | — |
| SECONDARY Ratio of TAK-915 Metabolite Cmax to TAK-915 Cmax in SRD and MRD Cohorts |
0.230; 0.248; 0.254; 0.273; 0.212; 0.267 | — |
| SECONDARY Ratio of TAK-915 Metabolite AUC(0-inf) to TAK-915 AUC(0-inf) in SRD Cohorts |
0.492; 0.475; 0.483; 0.576; 0.451 | — |
| SECONDARY Ratio of TAK-915 Metabolite Area Under the Plasma Concentration-Time Curve From Time 0 to Time Tau Over a Dosing Interval [AUC(0-tau)] Where Tau is the Length of the Dosing Interval to TAK-915 AUC(0-tau) in MRD Cohorts |
0.496; 0.640; 0.505 | — |
| SECONDARY Cmax: Maximum Observed Plasma Concentration for TAK-915 and TAK-915 Metabolite M-I in BA/FE Cohort |
337.0; 208.0; 143.4; 79.2; 48.9; 34.6 | — |
| SECONDARY AUClast: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-915 and TAK-915 Metabolite M-I in BA/FE Cohort |
8412.3; 7310.0; 5740.2; 3785.3; 2992.1; 2208.7 | — |
| SECONDARY AUC(0-inf): Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-915 and TAK-915 Metabolite M-I in BA/FE Cohort |
10155.2; 9414.5; 7151.5; 4727.2; 4145.2; 3011.6 | — |
| SECONDARY Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-915 and TAK-915 Metabolite M-I in BA/FE Cohort |
1.500; 3.000; 7.000; 2.250; 10.000; 24.000 | — |
| SECONDARY Terminal Elimination Half-life (t1/2) for TAK-915 and TAK-915 Metabolite M-I in BA/FE Cohort |
34.973; 45.359; 40.101; 39.937; 50.010; 48.406 | — |
| SECONDARY λz: Terminal Elimination Rate Constant for TAK-915 and TAK-915 Metabolite M-I in BA/FE Cohort |
0.0202; 0.0187; 0.0202; 0.0180; 0.0155; 0.0162 | — |
Eligibility Criteria
Inclusion Criteria
- In the opinion of the investigator, the participant is capable of understanding and complying with protocol requirements.
- The 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.
- Is a healthy man or woman, aged 18 to 55 years, inclusive at the time of informed consent and first study medication dose for all cohorts will be included. Note that Cohort 12 will enroll healthy, elderly men and women, aged 65 to 75 years, inclusive.
- Weighs at least 50 kg and has a body mass index (BMI) from 18.0 to 35.0 kg/m^2, inclusive at Screening.
- 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 with no childbearing potential, defined as the participant has been surgically sterilized (hysterectomy, bilateral oophorectomy or tubal ligation) or who are postmenopausal (defined as continuous amenorrhea of at least 2 y ears and follicle stimulating hormone (FSH) >40 IU/L).
Exclusion Criteria
- Has received any investigational compound within 30 days prior to the first dose of study medication.
- Has received TAK-915 in a previous clinical study or as a therapeutic agent.
- Is an immediate family member, study site employee, or is in a dependent relationship with a study site employee who is involved in the conduct of this study (eg, spouse, parent, child, sibling) or may consent under duress.
- Has uncontrolled, clinically significant neurologic, cardiovascular, pulmonary, hepatic, renal, metabolic, gastrointestinal, urologic, immunologic, endocrine disease, or psychiatric disorder, or other abnormality, which may impact the ability of the participant to participate or potentially confound the study results.
- Has a known hypersensitivity to any component of the formulation of TAK-915 and/or midazolam.
- If female, the participant is of childbearing potential (eg. premenopausal, not sterilized).
- Has a positive urine drug result for drugs of abuse at Screening or Check-in (Day 1).
- Has a history of drug abuse (defined as any illicit drug use) or a history of alcohol abuse 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.
- Has taken any excluded medication, supplements, or food products during the time periods listed in the Excluded Medications and Dietary Products table.
- Is pregnant or lactating or intending to become pregnant before, during, or within 12 weeks after participating in this study ; 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 after the last dose of study medication.
- 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-915, 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.
- Has mental retardation or medical condition that can cause cognitive impairment.
- Has current or recent (within 6 months) gastrointestinal disease that would be expected to
Data sourced from ClinicalTrials.gov (NCT02461160). 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. Informational only — not medical advice.