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

Healthy Subjects Clinical Trial

Official title:

An Exploratory Open Label, Three-way Crossover Study to Compare the Pharmacokinetic Profiles of Three Different YM178 Modified Release (OCAS) Formulations Under Fasted and Fed Conditions With YM178 Immediate Release (IR) Formulation Under Fasted Conditions in Healthy Subjects

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01646294
• Other study ID #: 178-CL-030
• Secondary ID: 2004-003876-12
• Status: Completed
• Phase: Phase 1
• First received: July 18, 2012
• Last updated: July 1, 2013
• Start date: January 2005
• Est. completion date: May 2005

Study information

• Verified date: July 2013
• Source: Astellas Pharma Inc
• Contact: n/a
• Is FDA regulated: No
• Health authority: Netherlands: Medical Ethics Review Committee (METC)
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 34
• Est. completion date: May 2005
• Est. primary completion date: May 2005
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 55 Years

Eligibility

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 ß-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

Allocation: Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Disease
• Healthy Subjects
• Pharmacokinetics of YM178

Intervention

Drug:
• YM178 modified release (OCAS)
oral
• YM178 immediate release (IR)
oral

Locations

Country	Name	City	State
Netherlands	Pharma Bio-Research B.V.	Zuidlaren

Sponsors (1)

Lead Sponsor	Collaborator
Astellas Pharma Europe B.V.

Country where clinical trial is conducted

Netherlands, 

References & Publications (1)

Lee J, Zhang W, Moy S, Kowalski D, Kerbusch V, van Gelderen M, Sawamoto T, Grunenberg N, Keirns J. Effects of food intake on the pharmacokinetic properties of mirabegron oral controlled-absorption system: a single-dose, randomized, crossover study in healthy adults. Clin Ther. 2013 Mar;35(3):333-41. doi: 10.1016/j.clinthera.2013.02.014. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Pharmacokinetics profile of OCAS and IR assessed by plasma concentration	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)	Day 1 & Day 6 - Day 8	No
Primary	Pharmacokinetics profile of OCAS assessed by plasma concentration	AUC0-24h (Area under the plasma concentration - time curve from t=0 to t=24h) Cmax, Tmax and Ctrough	Day 8	No
Primary	Pharmacokinetics profile of IR assessed by plasma concentration	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	Day 8	No
Secondary	Monitoring of safety parameters through assessment of vital signs, adverse events, Electrocardiogram (ECG) and clinical laboratory assessments		Baseline until Post Study Visit	No

External Links

•   Link to Results on JAPIC