A Study to Compare the Actions in the Body of Healthy Subjects of Three Modified Release Formulations of YM178 Under Fasted and Fed Conditions With One Immediate Release Formulation of YM178 Under Fasted Conditions

Astellas

Status and phase: Completed; Phase 1

Conditions: Healthy Subjects; Pharmacokinetics of YM178

Treatments: Drug: YM178 modified release (OCAS); Drug: YM178 immediate release (IR)

Study type: Interventional

Funder types: Industry

Identifiers

NCT01646294

178-CL-030

2004-003876-12 (EudraCT Number)

Details and patient eligibility

About

The purpose of the study is to investigate how quickly and to what extent YM178 is absorbed and eliminated from the body, and how well it is tolerated, when given in three different tablet formulations (sustained release) once a day with and without food, and to compare the results with the profile of the YM178 immediate release formulation taken twice daily without food.

Full description

Subjects reside in the clinical research unit for 3 periods of 11 days each, with a washout period of at least 7 days between treatment periods. . Each subject is treated with multiple oral doses of the IR formulation (b.i.d.) under fasted conditions and, OCAS-F, OCAS-M or OCAS-S formulation (q.d.) under fasted and fed conditions (high fat breakfast).

The study is completed with a post-study visit between 7 and 14 days after discharge of period 3.

Enrollment: 34 patients

Sex: Male

Ages: 18 to 55 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• Body weight between 60.0 and 100.0 kg, and BMI between 18.0 and 30.0 kg/m2

Exclusion criteria

• Known or suspected hypersensitivity to β-adrenergic receptor agonists or constituents of the formulations used
• Clinically significant elevation of serum creatinine or liver enzymes as evidenced by creatinine and/or abnormal serum bilirubin
• Any clinically significant history of asthma, eczema, any other allergic condition or previous severe hypersensitivity to any drug
• Any clinically significant history of upper gastrointestinal symptoms in the 4 weeks prior to the first admission to the Research Unit
• Any clinically significant history of any other disease or disorder -gastrointestinal, cardiovascular, respiratory, renal, hepatic, neurological, dermatological, psychiatric or metabolic
• QTcB interval of >430 msec at screening (mean QTcB of two measurements>430msec)
• Abnormal pulse rate measurement (<40 or >90 bpm) at the pre-study visit after subject has been resting in supine position for 5 min
• Abnormal blood pressure measurements taken at the pre-study visit after subject has been resting in supine position for 5 minutes
• Positive orthostatic test at screening i.e. any symptoms of dizziness, light-headedness etc. and a fall of > 20 mmHg in systolic blood pressure after 2 min standing (as outlined in section 12.5) and an increase in pulse rate of ≥ 20 bpm
• History of smoking more than 10 cigarettes (or equivalent amount of tobacco) per day within 3 months prior to first admission to the Research Unit.
• History of drinking more than 21 units of alcohol per week within 3 months prior to first admission to the Research Unit
• Donation of blood or blood products (more than 400 ml) within 3 months prior to first admission to the Research Unit or plasmapheresis within 4 weeks preceding the start of this study
• Positive serology test for HBsAg, HAV IgM, anti-HCV or anti-HIV 1+2
• Subject who is not willing to complete standard FDA high fat breakfast

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: None (Open label)

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34 participants in 3 patient groups

OCAS-F

Experimental group

Description:

YM178 OCAS tablet (OCAS-Fast) taken orally under fasted and fed condition

Treatment:

Drug: YM178 immediate release (IR)

Drug: YM178 modified release (OCAS)

OCAS-S

Experimental group

Description:

YM178 OCAS tablet (OCAS-Slow) taken orally under fasted and fed condition

Treatment:

Drug: YM178 immediate release (IR)

Drug: YM178 modified release (OCAS)

OCAS-M

Experimental group

Description:

YM178 OCAS tablet (OCAS-Medium) taken orally under fasted and fed condition

Treatment:

Drug: YM178 immediate release (IR)

Drug: YM178 modified release (OCAS)