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

Amgen

Status and phase: Terminated; Phase 1

Conditions: Ulcerative Colitis

Treatments: Drug: Amg 181

Study type: Interventional

Funder types: Industry

Identifiers

NCT01164904

20090107

Details and patient eligibility

About

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)

Enrollment: 72 patients

Sex: All

Ages: 18 to 55 years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion criteria

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Single Group Assignment

Masking: Double Blind

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72 participants in 1 patient group

Experimental

Experimental group

Description:

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.

Treatment:

Drug: Amg 181