Safety, Tolerability, and Pharcodynamics of AMG 853 in Adolescents With Asthma

Inclusion Criteria:

- Male and/or female subjects ≥12 to < 18 years of age (for Cohorts 1, 2, and 3 as
indicated in the study design).

- Male and/or non-reproductive female subjects between 18 and 50 years of age,
inclusive (for cohort 4).

- Females of non-reproductive potential must have documented medical history (ie,
postmenopausal by history - no menses for 1 year - and follicle-stimulating hormone
value (FSH) consistent with postmenopausal status per laboratory ranges; OR history
of hysterectomy; OR history of bilateral tubal ligation; OR history of bilateral
oophorectomy).

- Females of child-bearing potential and females who cannot document non-reproductive
potential must agree to use highly effective methods of birth control for the
duration of the study and for 2 weeks after study drug administration. Males whose
partners are of child bearing potential must agree to use highly effective methods of
birth control for the duration of the study and continuing for 12 weeks after study
drug administration. Highly effective methods of birth control (i.e., those with a
failure rate of less than 1% per year) include sexual abstinence (males, females),
vasectomy or a condom supplemented with the use of a spermicide (males) and occlusive
cap (diaphragm or cervical/vault caps), hormonal birth control, or intrauterine
device (IUD) used by the female partner.

- Male subjects whose partners become pregnant during the study must practice sexual
abstinence or use a condom with spermicide for two weeks following study drug
administration to ensure the unborn child is not potentially exposed to AMG 853 via
semen. The pregnant partner information will be reported to Amgen per the Pregnancy
Notification Worksheet.

- Intermittent or mild to moderate persistent asthma for the past 3 months (as defined
by the 2004 Global Initiative for Asthma [GINA] guidelines).

- On a stable pharmacologic regimen for the treatment of asthma for at least 3 months
prior to study enrollment and does not anticipate any change to the regimen during
the course of the study.

- Forced Expiry Volume in 1 second (FEV1) at screening visit ≥ 70% of predicted normal
value (without aid of bronchodilator).

- FEV1 reversibility greater than or equal to 12% from baseline within 30 minutes of
inhaled (up to 400 μg) or nebulized (up to 5 mg) albuterol at the office screening
visit. Subjects unable to demonstrate reversibility during screening, must provide
the most recent evidence of documented reversibility to the Amgen Medical Monitor and
the principal investigator for review.

- Clinically acceptable physical examination, electrocardiogram (ECG), and clinical
laboratory test values for the population tested. Any abnormal clinical laboratory
results and/or ECG values must be discussed with the Sponsor.

Exclusion Criteria:

- History or evidence of clinically significant disorder, condition or disease that, in
the opinion of the investigator or Amgen physician, would pose a risk to subject
safety or interfere with the study evaluation, procedures, or completion.

- Experienced an asthma exacerbation (defined as a disease episode resulting in
treatment in an emergency room or urgent care facility, or an episode treated with
oral corticosteroids) during the 3 months prior to study enrollment.

- Hospitalized for asthma during the 6 months prior to study enrollment; or ever
intubated for the treatment of asthma.

- Use of oral corticosteroids within 3 months prior to study enrollment.

- Evidence of recent (within 2 weeks of study enrollment) or current signs or symptoms
of an upper respiratory infection (eg, viral, bacterial).

- Known positive tuberculin skin test (if not treated with appropriate
chemoprophylaxis) or untreated exposure to a patient with active tuberculosis.

- History of autoimmune disorder (eg, rheumatoid arthritis, systemic lupus).

- Creatinine clearance within the screening period of less than 80 mL/min as calculated
by the Cockcroft-Gault method.

- History of clinically significant cardiovascular, renal, hepatic or respiratory
disease other than asthma.

- History suggestive of esophageal, gastric, or duodenal ulceration or bowel disease
(including but not limited to peptic ulceration, gastrointestinal bleeding,
ulcerative colitis, Crohn's disease or irritable bowel syndrome), or a history of
gastrointestinal surgery (excluding uncomplicated appendectomy).

- Any positive test for cotinine (tobacco use) on the day before dosing. A positive
cotinine level is defined as any level exceeding the upper limit of normal as per
local laboratory reference ranges.

- Known substance abuse (eg, alcohol, licit or illicit drugs) within 1 year of dosing
as defined by Diagnostic and Statistical Manual version 4, text revsion (DSM-IV-TR)
criteria.

- Any positive test for drugs and or alcohol use on the day before dosing (day -1). For
subjects of legal drinking age, alcohol should not be consumed within 48 hours of day
-1 and throughout the study. Alcohol use is not permitted for subjects below the
legal drinking age.

- Positive pregnancy test at screening or day -1.

- Females who are lactating or breastfeeding.

- with pregnant partners.

- Inability or unwillingness to swallow tablets.

- A history of malignancy of any type, other than surgically excised non-melanomatous
skin cancers or in situ cervical cancer within 5 years before the day of dosing.

- Donated greater than 500 mL of blood or blood products within 60 days of dosing.

- Subjects who have received any investigational drug (or have used an investigational
device) within the 30 days before receiving the first dose of study medication, or at
least 5 elimination half-lives (whichever is longer).

- Subjects who were previously exposed to AMG 853.

- Use of any prescription (eg, angiotensin inhibitors) or non-prescription [eg,
non-steroidal anti-inflammatory drugs (NSAIDS)] medications including asthma
medications (eg, inhaled cromolyn, inhaled ipratropium, inhaled tiotropium,
theophylline) within 7 days of study start with the exception of inhaled
corticosteroid therapy (≤ 660 μg/day fluticasone or ≤ 480 μg/day beclomethasone, or
equivalent), inhaled short-acting and long-acting β-2 agonists, and montelukast.

- Use of any over-the-counter or prescription medications (specifically including, but
not limited to antacids, H2- blockers, and proton pump inhibitors, aspirin or other
NSAIDS within 28 days of dosing. Acetaminophen (up to 2 g per day) for analgesia and
hormone replacement therapy (eg, estrogen) will be allowed.

- Use of any known inhibitors of CYP3A4/P-gp such as ketoconazole, itraconazole, HIV
protease inhibitors, nefazadone, cyclosporine, erythromycin, clindamycin,
tetracycline, and clarithromycin within 14 days or 5 half lives, whichever is longer;
or grapefruit juice or grapefruit containing products within 7 days prior to
investigational product administration.

- Use of any known CYP inducers such as rifampin, oral corticosteroids, or
anticonvulsants within 30 days or 5 half-lives, whichever is longer, before
investigational product administration.

- All herbal medicines (eg, St. John's Wort), vitamins, and supplements consumed by the
subject within 30 days prior to the first dose of investigational product, and
continued use if appropriate, will be reviewed by the Principal Investigator and the
Amgen Medical Monitor.

- History of hypersensitivity or allergic reaction to sulfonamide drugs.

- Positive for human immunodeficiency virus (HIV) antibodies, hepatitis B surface
antigen, or hepatitis C antibodies.

- Known history of Gilbert's syndrome.

- Unwilling or unable to return to the research facility for follow-up assessments as
required per protocol.

- Any other condition that might reduce the chance of obtaining data (eg, known poor
compliance) required by the protocol or that might compromise the ability to give
truly informed consent.