Safety and Pharmacokinetics Study of XOMA 052 in Subjects With Type 2 Diabetes Mellitus

• Status: Completed
• Trial end date: 2010-02-01
• Target enrollment: 0
• Participant gender: All

Summary

The purpose of this study is to evaluate the safety and pharmacokinetics (PK) of XOMA 052 in subjects with stable Type 2 Diabetes Mellitus (T2D).

The study is a dose-escalation study designed to evaluate route of administration (intravenous or subcutaneous), doses, and dosing regimens for future studies.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: XOMA (US) LLC

Criteria

Inclusion Criteria:

• American Diabetes Association (ADA) diagnostic criteria for T2D - Fasting blood glucose concentration ≥ 126 mg/dL (≥ 7.0 mmol/L) (must be measured within 35 days prior to Day 0) OR Symptoms of hyperglycemia (e.g., thirst, polyuria, weight loss, visual blurring) AND a casual/random plasma glucose value of ≥ 200 mg/dL (≥ 11.1 mmol/L) (must be measured within 35 days prior to Day 0)

• HbA1c ≥ 7.5% and ≤ 12% (DCCT standard)

• Current T2D of duration > 6 months at Screening

• T2D and other diseases must be stable. Stable disease is defined as disease that is judged stable by the investigator and which did not require a change in medications or dosing level on 4 or more consecutive days or 7 days in total within 35 days prior to Day 0.

• Age ≥ 18 and ≤ 70 at Screening

• Weight ≥ 80 lbs (36.3 kg) and ≤ 325 lbs (147.4 kg)

• BMI ≥ 23 and ≤ 40 kg/m2

• For female subjects of child-bearing age, a negative serum pregnancy test. For subjects with reproductive potential, a willingness to use contraceptive measures adequate to prevent the subject or the subject's partner from becoming pregnant during the study.

• Agree not to change diet and exercise regimen during the trial

Exclusion Criteria:

• Use of the following medications - Anti-inflammatory therapy other than aspirin ≤ 100 mg/day; Immunosuppressive treatment; Beta 2 and non-selective adrenergic blockers (Note: selective beta 1 blockers are permitted); Thiazolidinediones; Glucagon-like peptide (GLP) agonists including DPP4 inhibitors

• Change in medication for diabetes within 35 days prior to Day 0, defined as a change in dosing level on 4 or more consecutive days or 7 days in total

• Fasting C-peptide < 400 pM (< 1.20 μg/L)

• Hemoglobin < 8.0 g/dL, WBC < 3.0 X 103/mm3, platelet count < 125 X 103/mm3, creatinine > 1.5 mg/dL, AST/ALT > 2 X ULN, alkaline phosphatase > 2 X ULN

• Positive for GAD65 or IA-2 auto-antibodies

• Known HIV antibody, hepatitis B surface antigen, and/or hepatitis C antibody

• History of malignancy within 5 years prior to study entry other than carcinoma in situ of the cervix, or adequately treated, non-metastatic squamous or basal cell carcinoma of the skin

• History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies

• History of tuberculosis, positive PPD test, active atopic disease requiring medication, or asthma

• Infectious disease - CRP > 30 mg/L, fever, or infection requiring treatment with antibiotics within 3 weeks prior to Screening; History of recurrent infection or predisposition to infection; Active leg or foot ulcer

• Immunodeficiency

• Female subjects who are pregnant, planning to become pregnant during the course of the study, or breast-feeding

• History or symptoms of a demyelinating disease

• Clinically significant diabetic macular edema and/or proliferative diabetic retinopathy by history or fundoscopy

• Receipt of a live (attenuated) vaccine within 3 months prior to Screening

• Major surgery within 35 days prior to Day 0

• Participation in an investigational drug or device trial within 30 days prior to Screening

• Use of a therapeutic monoclonal antibody within 90 days prior to Screening

• Any condition which, in the opinion of the investigator, would jeopardize the subject's safety following exposure to the study drug