Pharmacokinetics of Oral Mirabegron With Different Release Rates Versus Intravenous (IV) Mirabegron

Subjects will be randomly assigned to one of three oral mirabegron doses and then randomly
assigned to one of three oral mirabegron doses and then randomly assigned to one of six
treatment sequences.

For all subjects the first treatment will be a reference IV dose. Treatments 2, 3, and 4 will
be a random order of slow, fast and target release oral doses of mirabegron. Treatment 5 will
be a target release dose of mirabegron from a different batch.

There will be at least 10 day washout between dose administrations.

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

- The subject must have a normal or clinically nonsignificant 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 should have a negative pregnancy test result

- The subject must have negative test results for drugs of abuse and alcohol screens

- The subject must have a 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

- 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 (within 30 days 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 beverages/food
(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