Multiple Ascending Dose Study in Subjects With Type 2 Diabetes

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics following ascending multiple doses of AMG 876 in subjects with type 2 diabetes.

Official Title
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A Randomized, Double-blind, Placebo-controlled, Ascending Multiple-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: Male and female subjects ≥ 18 to ≤ 65 years of age at the time of randomization Female subjects must be of documented non-reproductive potential Diagnosed with type 2 diabetes HbA1c ≥ 6.5% and ≤ 10% Fasting C-peptide value ≥ 0.8 ng/mL Body mass index (BMI) between ≥ 25.0 and ≤ 40.0 kg/m2 at screening Exclusion Criteria: Female subjects who are lactating/breastfeeding or who plan to breastfeed while on study through 4 weeks after receiving the last dose of study drug. Male subjects with partners who are pregnant or planning to become pregnant while the subject is on study through 4 weeks after receiving the last dose of study drug Evidence or history at screening of diabetic complications with significant end-organ damage, eg, proliferative retinopathy and/or macular edema, estimated glomerular filtration rate < 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 atrial or ventricular etiology, unexplained syncope, or syncope/seizures related to arrhythmia Uncontrolled hypertension (systolic blood pressure ≥ 150 mmHg or diastolic blood pressure ≥ 90 mmHg) either on or off therapy at screening Triglycerides ≥ 500 mg/dL (5.64 mmol/L) at screening Hepatic liver enzymes ALT, AST, alkaline phosphatase (ALP), or total bilirubin (TBIL) levels > 1.5 times the upper limit of normal (ULN) at screening Fasting blood glucose > 270 mg/dL at the screening visit Positive for human immunodeficiency virus (HIV) antibodies, hepatitis B surface antigen (HbsAg), or hepatitis C virus antibodies (HepCAb) 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 multiple doses of study drug administered SC<br>|
| Placebo Comparator: Placebo<br> | Drug: AMG 876<br>* Ascending multiple doses of study drug administered SC<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, laboratory analytes, and ECGs | 43 Days (Cohorts 1, 3, 5 and 7), 57 Days (Cohorts 2, 4, 6 and 9) or 71 Days (Cohort 8). | 
| Subject incidence of anti-AMG 876 antibodies | Laboratory analytes | 43 Days (Cohorts 1, 3, 5 and 7), 57 Days (Cohorts 2, 4, 6 and 9) or 71 Days (Cohort 8). | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AMG 876 serum PK parameters | Concentration-time profiles for AMG 876 | 43 Days (Cohorts 1, 3, 5 and 7), 57 Days (Cohorts 2, 4, 6 and 9) or 71 Days (Cohort 8). | 
| 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 non-esterified fatty acid concentrations); Fasting lipid levels (total cholesterol, low-density lipoprotein [LDL], high-density lipoprotein [HDL], and triglycerides); The following 7-point SMBG parameters: pre-meal average blood glucose, post-meal average blood glucose, 7-point average blood glucose, post-meal excursion, post-meal excursion average; Body weight, 24 hour weighted mean glucose(cohort 9 only) | 43 Days (Cohorts 1, 3, 5 and 7), 57 Days (Cohorts 2, 4, 6 and 9) or 71 Days (Cohort 8). | 

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