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

Ulcerative Colitis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01164904
• Other study ID #: 20090107
• Status: Terminated
• Phase: Phase 1
• First received: July 1, 2010
• Last updated: July 23, 2013
• Start date: July 2010
• Est. completion date: March 2013

Study information

• Verified date: July 2013
• Source: Amgen
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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)

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 72
• Est. completion date: March 2013
• Est. primary completion date: January 2013
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 55 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Colitis
• Colitis, Ulcerative
• Ulcer
• Ulcerative Colitis

Intervention

Drug:
• Amg 181
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.

Locations

Country	Name	City	State
Australia	Research Site	Adelaide	South Australia
Australia	Research Site	Herston	Queensland
Australia	Research Site	Nedlands	Western Australia
Australia	Research Site	Prahran	Victoria
New Zealand	Research Site	Auckland
New Zealand	Research Site	Christchurch
United States	Research Site	Danbury	Connecticut
United States	Research Site	Duncansville	Pennsylvania
United States	Research Site	Glendale	California
United States	Research Site	Plymouth	Minnesota

Sponsors (1)

Lead Sponsor	Collaborator
Amgen

Countries where clinical trial is conducted

United States,  Australia,  New Zealand, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Yes
Secondary	To characterize the pharmacokinetics (PK) of ascending single doses of AMG 181		Through study completion	No
Secondary	To characterize the pharmacodynamic (PD) effects of AMG 181 on receptor occupancy and on cell counts in selected lymphocyte subset populations		Through study completion	No

External Links

•   AmgenTrials clinical trials website