Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of AMG 181 in Healthy Subjects and Subjects With Mild to Moderate Ulcerative Colitis

Study Overview
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Brief Summary
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To assess the safety and tolerability of single subcutaneous (SC) and intravenous (IV) doses of AMG 181 in healthy subjects and of a single SC dose in subjects with mild to moderate ulcerative colitis (UC)

Official Title
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A Phase 1, Randomized, Double-blind, Placebo-controlled, Ascending Single Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of AMG 181 in Healthy Subjects and Subjects With Mild to Moderate Ulcerative Colitis

Conditions
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Ulcerative Colitis

Intervention / Treatment
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* Drug: Amg 181


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy Volunteers Healthy male or female subjects of non-reproductive potential between 18 to 45 year-of -age Body Mass Index (BMI) between 18 and 34 kg/m2 Normal physical and neurological examination, clinical laboratory values and ECG Additional inclusion criteria apply Inclusion Criteria: Subjects with Mild to Moderate Ulcerative Colitis Male or female subjects between 18 to 55 year-of -age Body Mass Index (BMI) between 18 and 34 kg/m2 Diagnosis of Ulcerative Colitis for at least 2 months Active, mild to moderate disease as defined by an Ulcerative Colitis Disease Activity Index (UCDAI, aka Mayo score) score of 4 to 9 (inclusive), with a minimum sigmoidoscopy score of 1 Additional inclusion criteria apply Exclusion criteria: Healthy Volunteers 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 Recent or on-going infection(s) Underlying condition(s) that predisposes the subject to infections Additional exclusion criteria apply Exclusion criteria: Subjects with Mild to Moderate Ulcerative Colitis Disease limited to the rectum, i.e. within 20 cm of the anal verge Any prior gastrointestinal surgery Evidence of severe disease (as evidenced by an Hb concentration <11g/dL; toxic megacolon, or an UCDAI score≥10) Immunosuppressive therapy with either azathioprine, methotrexate, or mercaptopurine, within the past 3 months Prior exposure to a biologic agent or cyclosporine A Use of antibiotics within the past 2 weeks of screening and during screening period Use of topical (e.g. suppository or enema) mesalamine or steroids within two weeks prior to day 1 Additional exclusion criteria apply

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental<br>Ten escalating dose levels of AMG 181 administered as a single dose SC or IV in healthy volunteers and SC in subjects with mild-to-moderate ulcerative colitis. | Drug: Amg 181<br>* Ten escalating dose levels of AMG 181 administered as single dose SC or IV, in healthy volunteers and SC subjects with mild-to-moderate ulcerative colitis.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To assess the safety and tolerability of single subcutaneous (SC) and intravenous (IV) doses of AMG 181 in healthy subjects and of a single SC dose in subjects with mild to moderate ulcerative colitis (UC) |  | Through study completion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To characterize the pharmacokinetics (PK) of ascending single doses of AMG 181 |  | Through study completion | 
| To characterize the pharmacodynamic (PD) effects of AMG 181 on receptor occupancy and on cell counts in selected lymphocyte subset populations |  | Through study completion | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Inflammatory Bowel Disease, Amgen