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

NCT01646294 | Completed Phase 1

• 2 other identifiers: 178-CL-0302004-003876-12
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 1

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.

Conditions

Pharmacokinetics of YM178; Healthy Subjects

Keywords

Pharmacokinetics; Phase I; YM178; Modified release (Oral Controlled Absorption System (OCAS)); Immediate release (IR); Fasted conditions; Fed conditions

Outcome Measures

Primary Outcomes (3)

• 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

• 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

• 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

Secondary Outcomes (1)

• Monitoring of safety parameters through assessment of vital signs, adverse events, Electrocardiogram (ECG) and clinical laboratory assessments

  Baseline until Post Study Visit

Study Arms (3)

OCAS-F

EXPERIMENTAL

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

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

OCAS-S

EXPERIMENTAL

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

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

OCAS-M

EXPERIMENTAL

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

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

Interventions

YM178 modified release (OCAS) DRUG

oral

Also known as: mirabegron, Myrebtriq

OCAS-F; OCAS-M; OCAS-S

YM178 immediate release (IR) DRUG

oral

Also known as: mirabegron, Myrebtriq

OCAS-F; OCAS-M; OCAS-S

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• Astellas Pharma Europe B.V.: lead

Study Sites (1)

Pharma Bio-Research B.V.

Zuidlaren, 9471 GP, Netherlands

Location

Related 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.

  PMID: 23497763 BACKGROUND

MeSH Terms

Interventions

mirabegron

Study Officials

• Clinical Study Manager

  Astellas Pharma Europe B.V.

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 18, 2012
• First Posted: July 20, 2012
• Study Start: January 1, 2005
• Primary Completion: May 1, 2005
• Study Completion: May 1, 2005
• Last Updated: July 2, 2013

Record last verified: 2013-07

Locations

NL (1)