Clinical trial NCT01646294: 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
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
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
Lead sponsor: Astellas Pharma Inc
Sponsor class: INDUSTRY
First posted: 2012-07-20
Enrollment: 34
Sex: MALE
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

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.

Eligibility 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

Primary outcomes:
measure: Pharmacokinetics profile of OCAS and IR assessed by plasma concentration
timeFrame: Day 1 & Day 6 - Day 8
measure: Pharmacokinetics profile of OCAS assessed by plasma concentration
timeFrame: Day 8
measure: Pharmacokinetics profile of IR assessed by plasma concentration
timeFrame: Day 8
Secondary outcomes:
measure: Monitoring of safety parameters through assessment of vital signs, adverse events, Electrocardiogram (ECG) and clinical laboratory assessments
timeFrame: Baseline until Post Study Visit
Other outcomes:
Locations:
city: Zuidlaren
country: Netherlands
facility: Pharma Bio-Research B.V.
Study officials:
affiliation: Astellas Pharma Europe B.V.
name: Clinical Study Manager
role: STUDY_CHAIR
References:
citation: 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.