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

Type 2 Diabetes Clinical Trial

Official title:

A Phase 1/2a, Double-blind, Placebo-controlled Study of the Safety and Pharmacokinetics of XOMA 052 in Subjects With Type 2 Diabetes Mellitus

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00513214
• Other study ID #: X052073
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: August 7, 2007
• Last updated: September 30, 2011
• Start date: July 2007
• Est. completion date: February 2010

Study information

• Verified date: September 2011
• Source: XOMA (US) LLC
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 68
• Est. completion date: February 2010
• Est. primary completion date: June 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

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

Study Design

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

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Type 2 Diabetes

Intervention

Drug:
• XOMA 052
Part 1, Single IV infusion at one of six dose levels (mg/kg). Part 2, Single SC injection at one of three dose levels (mg/kg). Part 3, Three biweekly SC injections at one of two dose levels (mg/kg).
• Placebo
Part 1, Single IV infusion at one of six dose levels (mg/kg). Part 2, Single SC injection at one of three dose levels (mg/kg). Part 3, Three biweekly SC injections at one of two dose levels (mg/kg).

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
XOMA (US) LLC

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety assessed by pre- and post-treatment serial measurements of vital signs.		Part 1: Day 0 pre-treatment through Day 56. Part 2: Day 0 pre-treatment through Day 56. Part 3: Day 0 pre-treatment through Day 84.	No
Primary	Safety assessed by treatment-emergent adverse events.		Part 1: Day 0 post-treatment through Day 56. Part 2: Day 0 post-treatment through Day 56. Part 3: Day 0 post-treatment through Day 84.	No