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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Astellas Pharma Inc ( Astellas Pharma Europe B.V. )
ClinicalTrials.gov Identifier:
NCT01646294
First received: July 18, 2012
Last updated: July 1, 2013
Last verified: July 2013
  Purpose

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.


Condition Intervention Phase
Pharmacokinetics of YM178
Healthy Subjects
Drug: YM178 modified release (OCAS)
Drug: YM178 immediate release (IR)
Phase 1

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

Resource links provided by NLM:


Further study details as provided by Astellas Pharma Inc:

Primary Outcome Measures:
  • Pharmacokinetics profile of OCAS and IR assessed by plasma concentration [ Time Frame: Day 1 & Day 6 - Day 8 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Day 8 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Day 8 ] [ Designated as safety issue: No ]
    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:
  • Monitoring of safety parameters through assessment of vital signs, adverse events, Electrocardiogram (ECG) and clinical laboratory assessments [ Time Frame: Baseline until Post Study Visit ] [ Designated as safety issue: No ]

Enrollment: 34
Study Start Date: January 2005
Study Completion Date: May 2005
Primary Completion Date: May 2005 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: OCAS-F
YM178 OCAS tablet (OCAS-Fast) taken orally under fasted and fed condition
Drug: YM178 modified release (OCAS)
oral
Other Names:
  • mirabegron
  • Myrebtriq
Drug: YM178 immediate release (IR)
oral
Other Names:
  • mirabegron
  • Myrebtriq
Experimental: OCAS-S
YM178 OCAS tablet (OCAS-Slow) taken orally under fasted and fed condition
Drug: YM178 modified release (OCAS)
oral
Other Names:
  • mirabegron
  • Myrebtriq
Drug: YM178 immediate release (IR)
oral
Other Names:
  • mirabegron
  • Myrebtriq
Experimental: OCAS-M
YM178 OCAS tablet (OCAS-Medium) taken orally under fasted and fed condition
Drug: YM178 modified release (OCAS)
oral
Other Names:
  • mirabegron
  • Myrebtriq
Drug: YM178 immediate release (IR)
oral
Other Names:
  • mirabegron
  • Myrebtriq

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.

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01646294

Locations
Netherlands
Pharma Bio-Research B.V.
Zuidlaren, Netherlands, 9471 GP
Sponsors and Collaborators
Astellas Pharma Europe B.V.
Investigators
Study Chair: Clinical Study Manager Astellas Pharma Europe B.V.
  More Information

Additional Information:
Publications:
Responsible Party: Astellas Pharma Inc ( Astellas Pharma Europe B.V. )
ClinicalTrials.gov Identifier: NCT01646294     History of Changes
Other Study ID Numbers: 178-CL-030, 2004-003876-12
Study First Received: July 18, 2012
Last Updated: July 1, 2013
Health Authority: Netherlands: Medical Ethics Review Committee (METC)

Keywords provided by Astellas Pharma Inc:
Pharmacokinetics
Phase I
YM178
Modified release (Oral Controlled Absorption System (OCAS))
Immediate release (IR)
Fasted conditions
Fed conditions

ClinicalTrials.gov processed this record on July 20, 2014