A Pharmacokinetic Study of Lurasidone After Single Oral Administration in Healthy Subjects

Status

Completed

Phases

Phase 1

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT02174510

Enrollment

Registered

2014-06-25

Start date

2014-03-31

Completion date

2014-04-30

Last updated

2019-01-11

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Schizophrenia

Keywords

pharmacokinetic, lurasidone, single dose

Brief summary

To evaluate the pharmacokinetic (PK) characteristics of lurasidone after single oral administration of different doses in healthy Chinese subjects. To evaluate the safety and tolerability of lurasidone after single oral administration of different doses in healthy Chinese subjects.

Detailed description

Single administration, double-blinded, placebo-controlled (3 subjects in each group will take placebo) and 3 dose groups (20 mg, 40 mg and 80 mg). There are three groups which are 20mg lurasidone or placebo, 40mg lurasidone or placebo and 80mg lurasidone or placebo. This study comprises a screening period (between signing of the informed consent form and Day -2), baseline period (Day -1), treatment period (Days 1-3) and ending of study examination period (Days 8-11 after the last sample collection for PK evaluation).

Interventions

DRUG20mg lurasidone

single oral lurasidone or placebo in 30 minutes after beginning of the over 350 kcal breakfast on day 1.

DRUG40mg lurasidone

single oral lurasidone or placebo in 30 minutes after beginning of the over 350 kcal breakfast on day 1.

DRUG80mg lurasidone

single oral lurasidone or placebo in 30 minutes after beginning of the over 350 kcal breakfast on day 1.

DRUGplacebo

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

BASIC_SCIENCE

Masking

TRIPLE (Subject, Caregiver, Investigator)

Eligibility

Sex/Gender

MALE

Age

18 Years to 40 Years

Healthy volunteers

Yes

Inclusion criteria

1. After detailed explanations of study objectives, methods and procedures, anticipated efficacy, pharmacologic actions, risks and other relevant contents, subjects are aware of all relevant information related to this study and have signed the written informed consent form voluntarily. 2. Male subjects are 18≤ age \<40 years of age when signing the informed consent. 3. Subjects with body weight of 50.0≤ and ≤ 80.0 kg and BMI (body mass index) of 19.0≤ and \<24.0 at screening examination. 4. Subjects are able to comply with all requirements during this study period, receive various physical and laboratory examinations per study protocol, and report subjective symptoms.

Exclusion criteria

1. Based on the examination results during screening period, various physical and laboratory examinations performed 1 day before medication (Day-1 ) and before administration of study drug on the medication day, there are certain medical concerns on subject's health status in principal investigator's or study supervising physician's opinions (certain treatment or medical observation are deemed necessary). 2. Subjects with past diabetic history. 3. Subjects has an HbA1c level of \>6.2% at screening. 4. Subjects with history of gastrointestinal operations. 5. Because of subjects' past medical history of cardiovascular diseases, liver diseases, renal diseases, endocrine disorders, digestive diseases, hematologic diseases, respiratory diseases, mental illness, neurological disorders (especially epilepsy and other convulsive disorders) and other diseases, subjects are unsuitable to participate in this study in the principal investigator's or study supervising physician's opinions. 6. Subjects with past history of allergy to drugs. 7. Subjects have consumed grapefruit or food containing grapefruit ingredients between 7 days before medication (Day -7) and administration of study drug on the medication day (Day 1). Subjects have consumed food containing hypericum perforatum L. ingredients between 14 days before medication (Day-14) and administration of study drug on the medication day (Day 1). 8. Subjects have taken any drugs (including over-the-counter drugs) between 7 days before medication (Day\_-7) and administration of study drug on medication day. 9. Regular drinker (criteria are mean daily consumption ≥2 bottles of 640 mL beers or Chinese liquor≥150 mL). 10. Subjects are used to drink large amount (criteria are daily consumption\>1.8 L) of caffeine-containing beverages (e.g. coffee, black tea, green tea, coca cola or nutritional oral solution, etc). 11. Subjects have history of drug abuse or positive urine drug tests. 12. Subjects with positive immunologic test results. 13. Average amount of daily smoking\>20 cigarettes. 14. Subjects have taken other study drugs within 3 months (Day\_-90\ Day 1) before medication. 15. Subjects received lurasidone orally before. 16. Subjects have history of blood donations of 400 mL within 3 months (Day\_-90\ Day 1) before medication; 200 mL within 1 month (Day\_-30\ Day 1) before medication; or donation of blood components within 2 weeks (Day\_-14\ Day 1) before medication. 17. Subjects have consumed alcohol-containing food between 3 days before medication 3 (Day\_-3) and before administration of study drug on medication day. 18. Subjects can not tolerate venipuncture or have poor peripheral venous access. 19. Subjects are unwilling to abstain from vigorous exercise from Day\_-1 until discharge. 20. Other subjects who are unsuitable to participate in this study in principal investigator's or study supervising physician's opinions.

Design outcomes

Primary

Measure	Time frame	Description
Lurasidone Cmax	pre-dose,0.5,1,1.5,2,3,4,6,8,12,24,36,48 hours post-dose	Cmax：Maximum (peak) observed drug serum concentration.
Lurasidone AUC	pre-dose,0.5,1,1.5,2,3,4,6,8,12,24,36,48 hours post-dose	AUC：Area under the serum concentration-time curve
Lurasidone Tmax	pre-dose,0.5,1,1.5,2,3,4,6,8,12,24,36,48 hours post-dose	Tmax：Time to maximum (peak) drug serum concentration
Lurasidone λZ	pre-dose,0.5,1,1.5,2,3,4,6,8,12,24,36,48 hours post-dose	λZ：Elimination rate constant
Lurasidone t1/2	pre-dose,0.5,1,1.5,2,3,4,6,8,12,24,36,48 hours post-dose	t1/2 :Biological half life correlated with the elimination rate constant (kel) of semi-logarithmic concentration-time curve
Lurasidone MRT	pre-dose,0.5,1,1.5,2,3,4,6,8,12,24,36,48 hours post-dose	MRT：Mean residence time.
Lurasidone CL/F	pre-dose,0.5,1,1.5,2,3,4,6,8,12,24,36,48 hours post-dose	CL/F：Apparent total clearance.
Lurasidone VZ/F	pre-dose,0.5,1,1.5,2,3,4,6,8,12,24,36,48 hours post-dose	VZ/F: Apparent volume of distribution at terminal phase (correlated with λz)

Countries

China

Participant flow

Recruitment details

Total 72 subjects were screened at the clinical site after obtaining informed consent. The data of informed consent from the first subject was march 2014. A total of 37 subjects were enrolled into the study and were randomized to three test drug groups (8 to 20mg group, 8 to 40mg group, 12 to 80mg group), and 9 subjects received placebo.

Participants by arm

Arm	Count
20mg Lurasidone 20mg lurasidone: single oral lurasidone.	8
40mg Lurasidone 40mg lurasidone: single oral lurasidone.	8
80mg Lurasidone 80mg lurasidone: single oral lurasidone.	12
Placebo Subjects administered placebo tablet at the same time with each lurasidone group.	9
Total	37

Baseline characteristics

Characteristic	20mg Lurasidone	40mg Lurasidone	80mg Lurasidone	Placebo	Total
Age, Continuous	26.5 years STANDARD_DEVIATION 3.74	25.4 years STANDARD_DEVIATION 3.07	27.5 years STANDARD_DEVIATION 7.79	28.4 years STANDARD_DEVIATION 4.72	27.1 years STANDARD_DEVIATION 5.41
Sex: Female, Male Female	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Sex: Female, Male Male	8 Participants	8 Participants	12 Participants	9 Participants	37 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk	EG003 affected / at risk
deaths Total, all-cause mortality	— / —	— / —	— / —	— / —
other Total, other adverse events	5 / 8	7 / 8	12 / 12	5 / 9
serious Total, serious adverse events	0 / 8	0 / 8	0 / 12	0 / 9