Multiple Ascending Dose Study in Subjects With Type 2 Diabetes

Diabetes Mellitus Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01856881
• Other study ID #: 20100018
• Status: Terminated
• Phase: Phase 1
• First received: March 25, 2013
• Last updated: November 5, 2015
• Start date: March 2013
• Est. completion date: March 2015

Study information

• Verified date: November 2015
• Source: Amgen
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 86
• Est. completion date: March 2015
• Est. primary completion date: November 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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

Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2

Intervention

Drug:
• AMG 876
Ascending multiple doses of study drug administered SC

Locations

Country	Name	City	State
United States	Research Site	Chula Vista	California
United States	Research Site	Cincinnati	Ohio
United States	Research Site	Miramar	Florida
United States	Research Site	Overland Park	Kansas
United States	Research Site	Renton	Washington
United States	Research Site	San Antonio	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Amgen

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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).	Yes
Primary	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).	Yes
Secondary	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).	No
Secondary	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).	No

External Links

•   AmgenTrials clinical trials website