Multiple Ascending Dose Study in Subjects With Type 2 Diabetes

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

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.

Study Overview

• Status: Terminated
• Conditions: Diabetes Mellitus
• Intervention / Treatment: Drug: AMG 876

• Study Type: Interventional
• Enrollment (Actual): 86
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Chula Vista, California, United States, 91911
      • Research Site
  • Florida
    • Miramar, Florida, United States, 33025
      • Research Site
  • Kansas
    • Overland Park, Kansas, United States, 66212
      • Research Site
  • Ohio
    • Cincinnati, Ohio, United States, 45255
      • Research Site
  • Texas
    • San Antonio, Texas, United States, 78209
      • Research Site
  • Washington
    • Renton, Washington, United States, 98057
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 61 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: AMG 876; Ascending multiple doses of study drug administered SC
Active Comparator: AMG 876	Drug: AMG 876; Ascending multiple doses of study drug administered SC

What is the study measuring?

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).

Collaborators and Investigators

• Sponsor: Amgen

Publications and helpful links

General Publications

• Kaufman A, Abuqayyas L, Denney WS, Tillman EJ, Rolph T. AKR-001, an Fc-FGF21 Analog, Showed Sustained Pharmacodynamic Effects on Insulin Sensitivity and Lipid Metabolism in Type 2 Diabetes Patients. Cell Rep Med. 2020 Jul 21;1(4):100057. doi: 10.1016/j.xcrm.2020.100057. eCollection 2020 Jul 21.

Helpful Links

• AmgenTrials clinical trials website

Study record dates

Study Major Dates

• Study Start: March 1, 2013
• Primary Completion (Actual): November 1, 2014
• Study Completion (Actual): March 1, 2015

Study Registration Dates

• First Submitted: March 25, 2013
• First Submitted That Met QC Criteria: May 17, 2013
• First Posted (Estimate): May 20, 2013

Study Record Updates

• Last Update Posted (Estimate): November 6, 2015
• Last Update Submitted That Met QC Criteria: November 5, 2015
• Last Verified: November 1, 2015

More Information

Terms related to this study

• Keywords: Type 2 diabetes
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2
• Other Study ID Numbers: 20100018