Safety, Tolerability, and Pharmacokinetics of Multiple-Dose TAK-058 in Healthy Participants

Healthy Volunteers Clinical Trial

Official title:

A Phase 1, Randomized, Placebo-Controlled, Double-Blind, Safety, Tolerability, and Pharmacokinetic Study in Healthy Subjects After Multiple Oral Doses of TAK-058

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02389881
• Other study ID #: TAK-058-1002
• Secondary ID: U1111-1165-3644
• Status: Completed
• Phase: Phase 1
• First received: March 10, 2015
• Last updated: December 9, 2015
• Start date: March 2015
• Est. completion date: December 2015

Study information

• Verified date: December 2015
• Source: Takeda
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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 four treatment groups—which will remain undisclosed to the patient and study doctor during the study (unless there is an urgent medical need):

• TAK-058 25 mg

• TAK-058 75 mg

• TAK-058 150 mg

• TAK-058 300 mg

• Placebo (dummy inactive solution ) - this is an oral solution that looks like the study drug but has no active ingredient.

This single-centre trial will be conducted in the United States. The overall time to participate in this study is 40 days if assigned to TAK-058 25mg, 75mg or 150mg dose. 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 32 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 32
• Est. completion date: December 2015
• Est. primary completion date: December 2015
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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-058.

• 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.

• Has current or recent (within 6 months) gastrointestinal disease that would be expected to influence the absorption of drugs (ie, a history of malabsorption, any surgical intervention known to impact absorption [eg, bariatric surgery or bowel resection], esophageal reflux, peptic ulcer disease, erosive esophagitis, or frequent [more than once per week] occurrence of heartburn).

• Has a history of cancer or other malignancy, except basal cell carcinoma that has been in remission for at least 5 years prior to Day 1.

• Has a positive test result for hepatitis B surface antigen (HBsAg), antibody to hepatitis C virus (anti-HCV) or a known history of human immunodeficiency virus infection at Screening.

• Has poor peripheral venous access.

• Has donated or lost 450 mL or more of his or her blood volume (including plasmapheresis), or had a transfusion of any blood product within 45 days prior to Day 1.

• Has a Screening or Check-in (Day -1) abnormal (clinically significant [CS]) electrocardiogram (ECG).

• Has a supine blood pressure outside the ranges of 90 to 140 mm Hg for systolic and 60 to 90 mm Hg for diastolic, confirmed with one repeat testing within a maximum of 5 minutes, at the Screening Visit or Check-in (Day -1) Visit.

• Has a resting heart rate outside the range 50 to 100 bpm, confirmed with repeat testing within a maximum of 5 minutes, at the Screening Visit or Check-in (Day -1) Visit.

• Has a QT interval with Fridericia's correction method (QTcF) >450 ms (males) or >470 ms (females) or PR outside the range of 120 to 220 ms, confirmed with one repeat testing within a maximum of 5 minutes, at the Screening Visit or Check-in (Day -1) Visit.

• Has abnormal Screening or Check-in (Day -1) laboratory values that suggest a CS underlying disease or subject with the following lab abnormalities: ALT and/or AST >1.5 the upper limits of normal.

• Has a risk of suicide according to the investigator's clinical judgment (eg, per Columbia-Suicide Severity Rating Scale [C-SSRS]) or has made a suicide attempt in the previous 6 months.

• Has uncontrolled, CS neurologic, cardiovascular, pulmonary, hepatic, renal, metabolic, gastrointestinal, urologic, immunologic, endocrine disease, or psychiatric disorder, or other abnormality, which may impact the ability of the subject to participate or potentially confound the study results.

• Has used nicotine-containing products (including but not limited to cigarettes, electronic cigarettes, pipes, cigars, chewing tobacco, nicotine patch or nicotine gum) within 28 days prior to Check-in (Day -1). Cotinine test is positive at Screening or Check-in (Day -1).

Study Design

Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Healthy Volunteers

Intervention

Drug:
• TAK-058 25 mg
TAK-058 25 mg administered orally.
• TAK-058 75 mg
TAK-058 75 mg administered orally.
• TAK-058 150 mg
TAK-058 150 mg administered orally.
• Matching Placebo to TAK-058
Matching placebo to TAK-058 administered orally.
• TAK-058 300 mg
TAK-058 300 mg administered orally.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Takeda

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants Reporting One or More Treatment-Emergent Adverse Events	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.	Up to Day 40 for Cohort 5	Yes
Primary	Percentage of Participants Who Meet the TGRD Markedly Abnormal Criteria for Safety Laboratory Tests at least Once Post-Dose	The percentage of participants with any markedly abnormal standard safety laboratory values collected throughout study.	Up to Day 14 for Cohort 5	Yes
Primary	Percentage of Participants Who Meet the TGRD Markedly Abnormal Criteria for Vital Signs at least Once Post-Dose	The percentage of participants with any markedly abnormal standard vital sign values collected throughout study.	Up to Day 14 for Cohort 5	Yes
Secondary	Cmax: Maximum Observed Plasma Concentration for TAK-058	Maximum observed plasma concentration (Cmax) is the peak plasma concentration of a drug after administration, obtained directly from the plasma concentration-time curve.	Days 1-3, Days 7-10 for Cohorts 1-4	No
Secondary	AUC(0-tlqc): Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-058	(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]).	Days 1-3	No
Secondary	AUC(0-24): Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours Postdose for TAK-058	AUC(0-24is measure of area under the curve over the dosing interval (tau) (AUC(0-tau]), where tau is the length of the dosing interval - 24 hours in this study).	Days 1-2	No
Secondary	AUC(0-tau): Area Under the Plasma Concentration-time Curve from Time 0 to Time tau Over the Dosing Interval for TAK-058	Area under the plasma concentration-time curve during a dosing interval, where tau is the length of the dosing interval.	Days 10-11 for Cohorts 1-4	No