A Study to Assess Pharmacokinetic Interaction of Multiple Dose Ketoconazole on Single Dose YM178 Oral Controlled Absorption System (OCAS) in Healthy Adult Volunteers

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Astellas Pharma Inc
ClinicalTrials.gov Identifier:
NCT01476800
First received: November 18, 2011
Last updated: September 4, 2013
Last verified: November 2011
  Purpose

The purpose of this study is to assess the pharmacokinetic interaction of multiple-dose ketoconazole on single-dose YM178 OCAS and the safety and tolerability of YM178 OCAS alone and in combination with ketoconazole in healthy adult volunteers.


Condition Intervention Phase
Healthy Subjects
Pharmacokinetics of YM178
Drug: YM178 OCAS
Drug: Ketoconazole
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Crossover Assignment
Masking: Open Label
Official Title: A Phase 1, Open-Label, Two-Period, One-Sequence Crossover Study to Assess Pharmacokinetic Interaction of Multiple Dose Ketoconazole on Single Dose YM178 Oral Controlled Absorption System (OCAS) in Healthy Male and Female Adult Volunteers

Resource links provided by NLM:


Further study details as provided by Astellas Pharma Inc:

Primary Outcome Measures:
  • Pharmacokinetic (PK) variable for YM178: Area under the plasma concentration - time curve from time of dosing to infinity (AUCinf) [ Time Frame: Up to Day 7 in Period 1 and up to Day 10 in Perod 2 ] [ Designated as safety issue: No ]
  • PK Variable for YM178: Maximum concentration (Cmax) [ Time Frame: Up to Day 7 in Period 1 and up to Day 10 in Perod 2 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Safety assessed by recording of adverse events, vital signs, laboratory assessments, electrocardiograms (ECGs) and physical exams [ Time Frame: Up to Day 7 in Period 1 and up to Day 10 in Period 2 ] [ Designated as safety issue: No ]

Enrollment: 24
Study Start Date: July 2006
Study Completion Date: November 2006
Primary Completion Date: November 2006 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: YM178 OCAS alone Drug: YM178 OCAS
oral
Other Name: mirabegron
Active Comparator: Ketoconazole alone Drug: Ketoconazole
oral
Other Name: Nizoral
Experimental: YM178 OCAS and ketoconazole Drug: YM178 OCAS
oral
Other Name: mirabegron

Detailed Description:

A single oral dose of YM178 OCAS will be administered on 2 separate occasions: alone on Day 1 of Period 1 and during multiple- dosing of ketoconazole on Day 4 of Period 2. In Period 2, an oral dose of ketoconazole will be administered once daily on Days 1-9.

  Eligibility

Ages Eligible for Study:   19 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • The subject, if female, must be surgically sterile (must be documented), post-menopausal (defined as at least two years without menses), or must be using double-barrier contraception or a non-hormonal IUD
  • The subject, if female, must be non-lactating, and have a negative serum pregnancy test result during the study
  • The subject must be in good health
  • The subject must weigh at least 45 kg, and have a Body Mass Index (BMI) between 18 and 30 kg/m^2, inclusive
  • The subject must have normal clinical laboratory test results or, if abnormal, are not clinically significant
  • The subject must have a normal 12-lead electrocardiogram (ECG) (including normal interval durations). If abnormal, the interval durations must be deemed not clinically significant and must not exceed the following values: PR intervals must not exceed 220 milliseconds and QTc values must not exceed 450 milliseconds in Males or 470 milliseconds in females
  • The subject must have negative drug and alcohol toxicology screens during the study. Any subject who tests positive for drugs or alcohol during the study will be terminated

Exclusion Criteria:

  • The subject has a history of clinically significant illness (e.g., cardiovascular, hepatic, renal, or gastrointestinal abnormality within past 3 months that would preclude participation in the study
  • The subject is known to have hepatitis or is positive for hepatitis A antibody IgM, hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibody, or has a positive result to tests for HIV-1 and/or HIV-2 antibodies
  • The subject is known to have hypersensitivity to YM178, or ketoconazole or other imidazole compounds
  • The subject has a resting supine pulse <50 bpm or >90 bpm
  • The subject has orthostasis (change in pulse rate with orthostatic maneuver of >20 bpm or to a level ≥ 120 bpm)
  • The subject is taking any oral hormonal contraceptive
  • The subject is taking a potential inhibitor of CYP3A4 or CYP2D6
  • The subject has received or is anticipated to receive a prescription systemic or topical medication within past 14 days or any long-active treatments (e.g., depot formulation) within past 30 days
  • The subject has received any other-the-counter medication including herbal medicines within past 14 days (occasional use of acetaminophen of up to 2000 mg/day but not more than 4 days per week is permitted)
  • The subject is currently participating in another clinical trial and/or is taking or has been taking an investigational drug in the past 30 days (or 10 half-lives of the drug, whichever is longer)
  • The subject anticipates an inability to abstain from alcohol, or caffeine use, or from grapefruit and grapefruit juice from 48 hours prior to the administration of the first dose of YM178 on Day 1 of Period 1 and throughout the duration of the study
  • The subject has used tobacco-containing products and nicotine or nicotine-containing products in past six months
  • The subject consumes more than 5 units of alcoholic beverages (one unit is 12 ounces of beer, 4 ounces of wine or 1 ounce of spirits) per week or has a history of substance abuse, drug addiction, or alcoholism within past 2 years.
  • The subject has had any blood donation or significant loss of blood or has received transfusion of any blood or blood products within 56 days of study initiation or has donated plasma within 7 days of study initiation.
  • The subject has a history of psychiatric illness within past 10 years or is incapable of being compliant with the study procedures
  • The subject is unable to understand verbal and/or written English or any other language in which a certified translation of the informed consent is available
  • The subject has a history of benign prostatic hypertrophy or urinary incontinence
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01476800

Locations
United States, Nebraska
MDS Pharma Services (US) Inc.
Lincoln, Nebraska, United States, 68502
Sponsors and Collaborators
Astellas Pharma Inc
Investigators
Study Director: Senior Medical Director Astellas Pharma Global Development
  More Information

Additional Information:
No publications provided

Responsible Party: Astellas Pharma Inc
ClinicalTrials.gov Identifier: NCT01476800     History of Changes
Other Study ID Numbers: 178-CL-036
Study First Received: November 18, 2011
Last Updated: September 4, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Astellas Pharma Inc:
Drugs, Investigational
pharmacokinetics
Urinary Bladder, Overactive
YM178
Mirabegron

Additional relevant MeSH terms:
Ketoconazole
14-alpha Demethylase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antifungal Agents
Anti-Infective Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on April 14, 2014