Study of the Effect of Food on the Pharmacokinetics of Mirabegron

A Phase 1, Open-Label, Randomized, Single Oral Dose, Three-Way Crossover Study to Assess the Effect of Food on the Pharmacokinetics of Mirabegron

The purpose of this study is to assess the effect of food on the pharmacokinetics of a single oral dose of mirabegron in healthy male and female subjects.

Subjects will be assigned in a random order to receive 3 dosing regimens:

1. a single oral dose under a fasting condition;
2. a single oral dose with food (low fat breakfast);
3. a single oral dose with food (high fat breakfast).

Inclusion Criteria:

• The subject must weigh at least 45 kg and have a body mass index (BMI) between 20.0 and 32.0 kg/m2 , inclusive
• The subject must have a normal or clinically non-significant 12 lead ECG as well as normal or clinically non-significant laboratory test results
• Female subjects must be post-menopausal (defined as at least 2 years without menses), surgically sterile, or practicing effective contraception, and will continue to use effective contraception during the study period. All females must be non-lactating, and must have a negative pregnancy test result
• The subject must have negative test results for drugs of abuse and alcohol screens
• The subject must have good venous access in both arms

Exclusion Criteria:

• The subject has evidence of QTc interval >430 msec for male, >450 msec for female
• The subject has liver function test values (ALT, AST, or bilirubin) above the upper limit of normal
• The subject has a history or presence of psychiatric illness, serious active or recurrent infection, or any medical condition or disorder that precludes the subject from participating in the study
• The subject has a previous history of cancer other than basal cell carcinoma or Stage 1 squamous cell carcinoma that has not been in remission for at least 5 years
• The subject has donated or lost ≥ 450 mL blood within 56 days prior to study drug administration or has donated plasma within 7 days prior to study drug administration
• The subject has received or is anticipated to receive a prescription drug within 14 days prior to Day -1 of Period 1 (within 30 days 1 for any long acting treatments such as depot formulations). Subject has taken any over-the-counter (OTC) medications, including complementary and alternative medicines (except for oral contraceptives and occasional use of acetaminophen of up to 2000 mg/day but not more than 4 days per week) within 14 days
• The subject has consumed alcohol, xanthine derivative-containing food/beverages (tea, chocolate), grapefruit juice, grapefruit-containing products or Seville oranges (e.g., bitter marmalade) within 48 hours before admission into the unit
• The subject has used tobacco-containing products and nicotine-containing products within 6 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 is known to have hepatitis or HIV-1 and/or HIV-2, or is positive for hepatitis A antibody IgM, hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibody