Effect of Naloxegol on Gastric, Small Bowel, and Colonic Transit in Healthy Subjects

Inclusion criteria:

- Body Mass Index (BMI) between 19 and 30 kg/m^2 and absolute weight between 45 and 100
kg. for both males and females.

- Females who are non-pregnant, non-lactating, postmenopausal for at least one year (as
evidenced by last menses 12 months from Day 0), surgically sterile, or willing to use
a clinically-approved method of contraception from 35 days prior to Day 0 until 30
days after the last dose of study medication

- Males who are surgically sterile or willing to use a clinically approved method of
contraception from Day 0 until 30 days after the last dose of study medication.

- Absence of gastrointestinal symptoms unless deemed not clinically significant by the
Investigator.

- Able to understand and willing to sign informed consent

- Negative urine drug screen at screening

Exclusion criteria:

- Structural or metabolic diseases/conditions that affect the gastrointestinal system,
or functional gastrointestinal disorders. For screening, three or more "YES"
responses on the Bowel Disease Questionnaire will be used to exclude subjects with
irritable bowel syndrome.

- Use of drugs or agents within the past 2 weeks or planned use in the subsequent 4
weeks during the study period that: Alter GI transit including laxatives, magnesium
or aluminum-containing antacids, prokinetic, erythromycin, narcotics,
anticholinergics, tricyclic antidepressants, Selective serotonin re-uptake inhibitors
(SSRI) and newer antidepressants.

- Analgesic drugs including opiates, NSAID, cyclooxygenase-2 (COX 2) inhibitors

- Use of non-prescription or prescription medications within 7 days or within five
half-lives prior to Day 0 for that particular medication. Note: Low stable doses of
thyroid replacement, estrogen replacement, and birth control pills or depot
injections, and use of acetaminophen on as needed basis are permissible.

- A score of greater than or equal to 11 for either score obtained from the Hospital
Anxiety Depression Scale

- Positive urine drug screen at screening

- Female subjects who are pregnant or breast feeding.

- Clinical evidence (including physical exam, previous laboratory tests) or significant
cardiovascular, respiratory, renal, hepatic, gastrointestinal, hematological,
neurological, psychiatric, or other disease that interfere with the objectives of the
study. Patients with previously high transaminase levels (AST, ALT) may be retested
and if the results are less than 1.5 times the upper limit of normal will be included
as long as they do not have an underlying known liver disease.

- Symptoms of a significant clinical illness in the preceding two weeks.

- Participation in another clinical study within the past 30 days.

- Subjects known allergy or hypersensitive to multiple drug compounds (greater than or
equal to 3 drug compounds), naloxegol or opioid antagonists, codeine sulfate, eggs or
any components of the study medication

- Daily use of any tobacco products within 6 months prior to Day 0

- Previous exposure to naloxegol

- Any other conditions or prior therapy which, in the opinion of the Investigator,
would make the subject unsuitable for this study

- Contraindications to use of naloxegol in accordance with FDA guidance: suspected GI
obstruction or at increased risk of recurrent obstruction; concomitant use of strong
CYP3A4 inhibitors such as clarithromycin and ketoconazole

- Concomitant treatment with moderate CYP3A4 inhibitors (diltiazem, erythromycin,
verapamil) or strong CYP3A4 inducers (rifampin) or other opioid antagonists.

- History of substance abuse.