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

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

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)

Study Overview

• Status: Terminated
• Conditions: Ulcerative Colitis
• Intervention / Treatment: Drug: Amg 181

• Study Type: Interventional
• Enrollment (Actual): 72
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • Queensland
    • Herston, Queensland, Australia, 4006
      • Research Site
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Research Site
  • Victoria
    • Prahran, Victoria, Australia, 3004
      • Research Site
  • Western Australia
    • Nedlands, Western Australia, Australia, 6009
      • Research Site
• New Zealand
  • Auckland, New Zealand, 1023
    • Research Site
  • Christchurch, New Zealand, 8011
    • Research Site
• United States
  • California
    • Glendale, California, United States, 91206
      • Research Site
  • Connecticut
    • Danbury, Connecticut, United States, 06810
      • Research Site
  • Minnesota
    • Plymouth, Minnesota, United States, 55446
      • Research Site
  • Pennsylvania
    • Duncansville, Pennsylvania, United States, 16635
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: Double

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental; 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; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Amgen

Publications and helpful links

Helpful Links

• AmgenTrials clinical trials website

Study record dates

Study Major Dates

• Study Start: July 1, 2010
• Primary Completion (Actual): January 1, 2013
• Study Completion (Actual): March 1, 2013

Study Registration Dates

• First Submitted: July 1, 2010
• First Submitted That Met QC Criteria: July 15, 2010
• First Posted (Estimate): July 19, 2010

Study Record Updates

• Last Update Posted (Estimate): July 25, 2013
• Last Update Submitted That Met QC Criteria: July 23, 2013
• Last Verified: July 1, 2013

More Information

Terms related to this study

• Keywords: Inflammatory Bowel Disease; Amgen
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Gastrointestinal Diseases; Gastroenteritis; Colonic Diseases; Intestinal Diseases; Inflammatory Bowel Diseases; Ulcer; Colitis; Colitis, Ulcerative
• Other Study ID Numbers: 20090107