Study to Evaluate Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of AMG 181.

Study Overview
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Brief Summary
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To assess the safety and tolerability of multiple subcutaneous doses of AMG 181 in healthy subjects, in subjects with active ulcerative colitis, and in subjects with active Crohn's disease.

Official Title
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A Phase 1, Randomized, Double-Blind, Placebo-controlled, Ascending Multiple Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of AMG 181 in Healthy Subjects, in Subjects With Active Ulcerative Colitis, and in Subjects With Active Crohn's Disease.

Conditions
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Ulcerative Colitis, Crohn's Disease

Intervention / Treatment
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* Drug: AMG 181
* Other: Placebo for AMG 181


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Body Mass Index (BMI) between 18 and 34 kg/m2 Normal physical and neurological examination, clinical laboratory values and ECG Ulcerative Colitis Disease Activity Index (UCDAI, aka Mayo score) score of 4 to 10 (inclusive), with a minimum sigmoidoscopy score of 1; (for subjects with ulcerative colitis) Crohn's Disease Activity Index (CDAI) score of >150 and < 450 at screening (for subjects with Crohn's disease) Additional inclusion criteria apply Exclusion Criteria: History or evidence of a clinically significant disorder (including psychiatric), condition or disease that would pose a risk to subject safety or interfere with the study evaluations, procedures or completion History of malignancy of any type, other than in situ cervical cancer or surgically excised non-melanomatous skin cancers within the past 5 years Underlying condition(s) that predisposes the subject to infections Disease limited to the rectum, i.e. within 10 cm of the anal verge (for subjects with ulcerative colitis) Evidence of severe disease (as evidenced by an Hb concentration less or equal to 10g/dL; toxic megacolon, or an UCDAI score greater than 10) (for subjects with ulcerative colitis) Subject has short bowel syndrome (for subjects with Crohn's disease) Presence of an ostomy (for subjects with Crohn's disease) Presence of a fistula (for subjects with Crohn's disease) Additional exclusion criteria apply

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Placebo arm<br>Four escalating dose levels of AMG 181 administered as multiple doses of AMG 181 in healthy subjects, in subjects with active ulcerative colitis, and in subjects with active Crohn's disease. | Other: Placebo for AMG 181<br>* Four escalating dose levels of AMG 181 administered as multiple doses of AMG 181 in healthy subjects, in subjects with active ulcerative colitis, and in subjects with active Crohn's disease.<br>|
| Active Comparator: Active arm<br>Four escalating dose levels of AMG 181 administered as multiple doses of AMG 181 in healthy subjects, in subjects with active ulcerative colitis, and in subjects with active Crohn's disease. | Drug: AMG 181<br>* Four escalating dose levels of AMG 181 administered as multiple doses of AMG 181 in healthy subjects, in subjects with active ulcerative colitis, and in subjects with active Crohn's disease.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To assess the number of adverse events per subject, after multiple subcutaneous doses of AMG 181 in in healthy subjects, in subjects with active ulcerative colitis, and in subjects with active Crohn's disease. |  | 40 Weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To measure the area under the plasma concentration curve versus time of drug AMG 181. |  | 29 Weeks | 
| To assess receptor saturation percentages relative to baseline after multiple doses of AMG 181. |  | 29 Weeks | 
| To evaluate changes in peripheral blood T lymphocyte subsets counts relative to baseline after multiple doses of AMG 181. |  | 29 weeks |