Diabetes Mellitus
Conditions
Keywords
Type 2 diabetes
Brief summary
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.
Interventions
DRUGAMG 876
Ascending multiple doses of study drug administered SC
Sponsors
Amgen
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Subject incidence of treatment-emergent adverse events | 43 Days (Cohorts 1, 3, 5 and 7), 57 Days (Cohorts 2, 4, 6 and 9) or 71 Days (Cohort 8). | Physical examinations, vitals, laboratory analytes, and ECGs |
| Subject incidence of anti-AMG 876 antibodies | 43 Days (Cohorts 1, 3, 5 and 7), 57 Days (Cohorts 2, 4, 6 and 9) or 71 Days (Cohort 8). | Laboratory analytes |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| AMG 876 serum PK parameters | 43 Days (Cohorts 1, 3, 5 and 7), 57 Days (Cohorts 2, 4, 6 and 9) or 71 Days (Cohort 8). | Concentration-time profiles for AMG 876 |
| Pharmacodynamic parameters | 43 Days (Cohorts 1, 3, 5 and 7), 57 Days (Cohorts 2, 4, 6 and 9) or 71 Days (Cohort 8). | 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) |
Countries
United States
Outcome results
None listed