A Phase 1, Randomized, Placebo-Controlled, Double-Blind, Safety, Tolerability, and Pharmacokinetic Study in Healthy Subjects After Multiple Oral Doses of TAK-058
Overview
- Phase
- Phase 1
- Intervention
- TAK-058
- Conditions
- Healthy Volunteers
- Sponsor
- Takeda
- Enrollment
- 40
- Primary Endpoint
- Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Signs at Least Once Post-Dose
- Status
- Completed
- Last Updated
- 9 years ago
Overview
Brief Summary
The purpose of this study is to evaluate the safety, tolerability, and pharmacokinetics of multiple doses of TAK-058 in healthy non-elderly and elderly participants.
Detailed Description
The drug being tested in this study is TAK-058, which is under evaluation for the treatment of schizophrenia. This study will enroll approximately 32 healthy non-elderly and 8 healthy elderly participants. Participants will be randomly assigned (by chance, like flipping a coin) to one of the five treatment groups-which will remain undisclosed to the patient and study doctor during the study (unless there is an urgent medical need): * Cohort 1 Non-elderly Healthy: TAK-058 25 mg * Cohort 2 Non-elderly Healthy: TAK-058 75 mg * Cohort 3 Non-elderly Healthy: TAK-058 150 mg * Cohort 4 Elderly Healthy: TAK-058 25 mg * Cohort 5 Non-elderly Healthy: TAK-058 300 mg * Cohort 1-4 Non Elderly Placebo (dummy inactive solution) - this is an oral solution that looks like the study drug but has no active ingredient. * Cohort 5 Elderly Placebo This single-center trial will be conducted in the United States. The overall time to participate in this study is 40 days if assigned to Cohort 1 to 4. Participants will be confined to the clinic for 12 days, and will be contacted by telephone 11 and 30 days after last dose of study drug for a follow-up assessment (Days 21 and 40). The overall time to participate in this study is 14 days if assigned to Cohort 5. Participants will be confined to the clinic for 4 days, and will be contacted by telephone 14 days after last dose of study drug for a follow-up assessment (Day 14).
Investigators
Eligibility Criteria
Inclusion Criteria
- •Ages for this study are 18 to 60 years for non-elderly and 18 to 65 years for elderly.
- •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, which is defined as the subject has been surgically sterilized (hysterectomy, bilateral oophorectomy or tubal ligation) or who are postmenopausal (defined as continuous amenorrhea of at least 2 years and follicle-stimulating hormone \[FSH\]\>40 IU/L).
- •Weighs at least 45 kg (99 lbs) and has a body mass index (BMI) between 18.0 and 30.0 kg/m\^2, inclusive at Screening.
Exclusion Criteria
- •Has received any investigational compound within 30 days prior to the first dose of study medication.
- •Has received TAK-058 in a previous clinical study.
- •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 a known hypersensitivity to any component of the formulation of TAK-
- •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 6 months prior to the Screening Visit or is unwilling to agree to abstain from alcohol and drugs throughout the study.
- •Female participants of childbearing potential (premenopausal, non-sterilized), or has a positive pregnancy test.
- •Male participants that intend to donate sperm during the course of this study or for 12 weeks thereafter.
- •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 subject's medical history, physical examination, or safety laboratory tests giving reasonable suspicion of a disease that would contraindicate taking TAK-058, 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 previously had a seizure or convulsion (lifetime), including absence seizure and febrile convulsion.
Arms & Interventions
Cohort 1 Non-elderly Healthy: TAK-058 25 mg
TAK-058 25 mg solution, orally, once daily on Day 1 and Days 4 through 10, in non-elderly healthy participants.
Intervention: TAK-058
Cohort 2 Non-elderly Healthy: TAK-058 75 mg
TAK-058 75 mg solution, orally, once daily on Day 1 and Days 4 through 10, in non-elderly healthy participants.
Intervention: TAK-058
Cohort 3 Non-elderly Healthy: TAK-058 150 mg
TAK-058 150 mg solution, orally, once daily on Day 1 and Days 4 through 10, in non-elderly healthy participants.
Intervention: TAK-058
Cohort 4 Elderly Healthy: TAK-058 25 mg
TAK-058 25 mg solution, orally, once daily on Day 1 and Days 4 through 10, in elderly healthy participants.
Intervention: TAK-058
Cohort 5 Non-elderly Healthy: TAK-058 300 mg
TAK-058 300 mg solution, orally, once daily on Day 1, in non-elderly healthy participants.
Intervention: TAK-058
Cohorts 1, 2, 3 and 5 Non-elderly Healthy: Placebo
TAK-058 placebo-matching solution, orally, once daily on Day 1 and Days 4 through 10 (Cohorts 1, 2 and 3), or TAK-058 placebo-matching solution, orally, once on Day 1 (Cohort 5), in non-elderly healthy participants.
Intervention: TAK-058 Placebo
Cohort 4 Elderly Healthy: Placebo
TAK-058 placebo-matching solution, orally, once daily on Day 1 and Days 4 through 10, in non-elderly healthy participants.
Intervention: TAK-058 Placebo
Outcomes
Primary Outcomes
Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Signs at Least Once Post-Dose
Time Frame: Cohorts 1-4 Day 1 to Day 40; Cohort 5 Day 1 to Day 14
The percentage of participants with any markedly abnormal standard vital sign values collected throughout study. Vital signs included blood pressure (after 5 minutes supine and at 1 and 3 minutes after standing), pulse and oral temperature.
Percentage of Participants Who Experienced at Least 1 Treatment-Emergent Adverse Event
Time Frame: Cohorts 1-4 Day 1 to Day 40; Cohort 5 Day 1 to Day 14
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 (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug.
Percentage of Participants Who Meet the Markedly Abnormal Criteria for Safety Laboratory Tests at Least Once Post-Dose
Time Frame: Cohorts 1-4 Day 1 to Day 40; Cohort 5 Day 1 to Day 14
The percentage of participants with any markedly abnormal standard safety laboratory values (chemistry and hematology) collected throughout study.
Secondary Outcomes
- Mean Cmax: Maximum Observed Plasma Concentration for TAK-058(Day 1 predose and at multiple time points (up to 72 hours) postdose, and Day 10 predose and at multiple time points (up to 24 hours) postdose)
- Mean AUC24: Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours Postdose for TAK-058(Day 1 predose and at multiple time points (up to 24 hours) postdose)
- Mean AUClast: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-058(Day 1 predose and at multiple time points (up to 72 hours) postdose)
- Mean AUCτ: Area Under the Plasma Concentration-time Curve From Time 0 to Time Tau Over the Dosing Interval for TAK-058(Day 10 predose and at multiple time points (up to 24 hours) postdose)