Multiple Ascending Dose Study in Subjects With Type 2 Diabetes

Phase 1

Terminated

• Conditions: Diabetes Mellitus
• Interventions: Drug: AMG 876

• Registration Number: NCT01856881
• Lead Sponsor: Amgen

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2013-03
• Study First Submitted: 2013-03-25
• Study First Submitted QC: 2013-05-17
• Study First Posted: 2013-05-20
• Primary Completion: 2014-11
• Study Completion: 2015-03
• Status Verified: 2015-11
• Last Update Submitted: 2015-11-05
• Last Update Posted: 2015-11-06

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 86

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)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
AMG 876	AMG 876	-
Placebo	AMG 876	-

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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)

Trial Locations

Locations (1)

Research Site; 🇺🇸 Renton, Washington, United States