Single Ascending Dose Trial in Patients With Type 2 Diabetes

A Phase 1, Randomized, Double-Blind, Placebo-Controlled, Ascending Single Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of AMG 876 in Subjects With Type 2 Diabetes

The purpose of this study is to determine whether AMG 876 is safe and well tolerated in subjects with type 2 diabetes.

Study Overview

• Status: Terminated
• Conditions: Diabetes Mellitus
• Intervention / Treatment: Drug: AMG 876

• Study Type: Interventional
• Enrollment (Actual): 47
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Nebraska
    • Omaha, Nebraska, United States, 68154
      • Research Site
  • Texas
    • San Antonio, Texas, United States, 78209
    • San Antonio, Texas, United States, 78209
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 63 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Subject has provided written informed consent
• Men and women between the ages of 18 and 65, inclusive at the time of randomization
• Women must be of documented non-reproductive potential (ie, postmenopausal [see definition below]; OR history of hysterectomy; OR history of bilateral tubal ligation; OR history of bilateral oophorectomy).
• Diagnosed with type 2 diabetes
• HbA1c ≥ 6.5% and ≤ 10%
• Fasting C-peptide value ≥ 0.8 ng/mL
• Men must agree for the duration of the study and continuing for 4 weeks after the dose of study drug, to practice a highly effective method of birth control. Highly effective methods of birth control include sexual abstinence, vasectomy or a condom with spermicide (men) in combination with either barrier methods, hormonal birth control or IUD (women).
• Men must agree to not donate sperm for the duration of the study and continuing for 4 weeks after the dose of study drug.
• Body mass index between ≥ 25.0 kg/m2 and ≤ 40.0 kg/m2 at screening
• Negative screening test for alcohol and potential drugs of abuse at screening and day -2, unless medication is prescribed by a physician and approved by the principal investigator and Amgen medical monitor

Exclusion Criteria:

• Men with partners who are pregnant at the time of screening or men with partners who plan to become pregnant during the study
• Women who are pregnant or breastfeeding History or evidence of a clinically significant disorder, condition or disease that, in the opinion of the principal investigator or Amgen medical monitor would pose a risk to subject safety or interfere with the study evaluation, procedures or completion
• Evidence or history at screening of diabetic complications with significant end-organ damage, eg, proliferative retinopathy and/or macular edema, creatinine clearance < 60 mL/min/1.73m2 (calculated using the Modification of Diet in Renal Disease formula), or macroalbuminuria (ie, ≥ +1 proteinuria on urinalysis), diabetic neuropathy complicated by neuropathic ulcers, or severe autonomic neuropathy with gastroparesis, chronic diarrhea, or hypoglycemic unawareness
• Significant cardiac disease, including but not limited to evidence or history of coronary artery disease, unstable angina, congestive heart failure, known arrhythmias of ventricular etiology, unexplained syncope or syncope/seizures related to arrhythmia
• Positive for human immunodeficiency virus (HIV) antibodies, hepatitis B surface antigen (Hbs Ag), or hepatitis C virus antibodies
• An unstable medical condition, defined as having been hospitalized within 28 days before day -1, major surgery within 6 months before day -1, or otherwise unstable in the judgment of the investigator (eg, risk of complications or adverse events unrelated to study participation)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: AMG 876; Ascending single doses of study drug administered SC, with one cohort administered IV
Active Comparator: AMG 876	Drug: AMG 876; Ascending single doses of study drug administered SC, with one cohort administered IV

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Subject incidence of treatment-emergent adverse events	Physical examinations, vitals, clinical laboratories, and ECGs	29 days
Safety laboratory analytes, vital signs, and ECGs	laboratory analytes, vital signs, and ECGs	29 days
Subject incidence of anti-AMG 876 antibodies.	laboratories analytes	29 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AMG 876 serum PK parameters	Concentration-time profiles for AMG 876	29 days
Pharmacodynamic parameters:	Concentration of fasting glucose, insulin and c-peptide levels; Concentration-time profiles and AUC for metabolic parameters (eg, glucose, insulin, c-peptide, glucagon and free fatty acid concentrations) following a mixed meal tolerance test; Lipid levels (ie, total cholesterol, LDL, HDL, and triglycerides); Body weight.	29 days

Collaborators and Investigators

• Sponsor: Amgen

Publications and helpful links

Helpful Links

• AmgenTrials clinical trials website

Study record dates

Study Major Dates

• Study Start: November 1, 2011
• Primary Completion (Actual): July 1, 2012
• Study Completion (Actual): October 1, 2012

Study Registration Dates

• First Submitted: September 28, 2011
• First Submitted That Met QC Criteria: December 14, 2011
• First Posted (Estimate): December 15, 2011

Study Record Updates

• Last Update Posted (Estimate): February 15, 2013
• Last Update Submitted That Met QC Criteria: February 13, 2013
• Last Verified: February 1, 2013

More Information

Terms related to this study

• Keywords: Type 2 diabetes
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2
• Other Study ID Numbers: 20100015