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

Phase 1

Completed

• Conditions: Pharmacokinetics of YM178; Healthy Subjects
• Interventions: Drug: YM178 modified release (OCAS); Drug: YM178 immediate release (IR)

• Registration Number: NCT01646294
• Lead Sponsor: Astellas Pharma Europe B.V.

Brief Summary

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.

Detailed 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.

Study Timeline

• Study Start: 2005-01
• Primary Completion: 2005-05
• Study Completion: 2005-05
• Study First Submitted: 2012-07-18
• Study First Submitted QC: 2012-07-18
• Study First Posted: 2012-07-20
• Status Verified: 2013-07
• Last Update Submitted: 2013-07-01
• Last Update Posted: 2013-07-02

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 34

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
OCAS-S	YM178 modified release (OCAS)	YM178 OCAS tablet (OCAS-Slow) taken orally under fasted and fed condition
OCAS-F	YM178 modified release (OCAS)	YM178 OCAS tablet (OCAS-Fast) taken orally under fasted and fed condition
OCAS-F	YM178 immediate release (IR)	YM178 OCAS tablet (OCAS-Fast) taken orally under fasted and fed condition
OCAS-S	YM178 immediate release (IR)	YM178 OCAS tablet (OCAS-Slow) taken orally under fasted and fed condition
OCAS-M	YM178 modified release (OCAS)	YM178 OCAS tablet (OCAS-Medium) taken orally under fasted and fed condition
OCAS-M	YM178 immediate release (IR)	YM178 OCAS tablet (OCAS-Medium) taken orally under fasted and fed condition

Primary Outcome Measures

Name	Time	Method
Pharmacokinetics profile of OCAS and IR assessed by plasma concentration	Day 1 & Day 6 - Day 8	AUC0-12h (Area under the plasma concentration - time curve from t=0 to t=12h) Cmax (Maximum concentration), tmax (Time to attain Cmax) and Ctrough (Pre-dose plasma concentration)
Pharmacokinetics profile of OCAS assessed by plasma concentration	Day 8	AUC0-24h (Area under the plasma concentration - time curve from t=0 to t=24h) Cmax, Tmax and Ctrough
Pharmacokinetics profile of IR assessed by plasma concentration	Day 8	AUC0-12h , AUC12-24h (Area under the plasma concentration - time curve from t=12 to t=24h), AUC0-24h, PTR (Peak trough ratio), Cmax, Tmax and Ctrough

Secondary Outcome Measures

Name	Time	Method
Monitoring of safety parameters through assessment of vital signs, adverse events, Electrocardiogram (ECG) and clinical laboratory assessments	Baseline until Post Study Visit

Trial Locations

Locations (1)

Pharma Bio-Research B.V.; 🇳🇱 Zuidlaren, Netherlands