Single Ascending Dose Trial in Patients With Type 2 Diabetes

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

Official Title
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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

Conditions
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Diabetes Mellitus

Intervention / Treatment
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* Drug: AMG 876


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: AMG 876<br> | Drug: AMG 876<br>* Ascending single doses of study drug administered SC, with one cohort administered IV<br>|
| Placebo Comparator: Placebo<br> | Drug: AMG 876<br>* Ascending single doses of study drug administered SC, with one cohort administered IV<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Type 2 diabetes