Multiple Ascending Dose Study in Subjects With Type 2 Diabetes
Primary Purpose
Diabetes Mellitus
Status
Terminated
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
AMG 876
Sponsored by
About this trial
This is an interventional treatment trial for Diabetes Mellitus focused on measuring Type 2 diabetes
Eligibility Criteria
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)
Sites / Locations
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Placebo Comparator
Arm Label
AMG 876
Placebo
Arm Description
Outcomes
Primary Outcome Measures
Subject incidence of treatment-emergent adverse events
Physical examinations, vitals, laboratory analytes, and ECGs
Subject incidence of anti-AMG 876 antibodies
Laboratory analytes
Secondary Outcome Measures
AMG 876 serum PK parameters
Concentration-time profiles for AMG 876
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)
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01856881
Brief Title
Multiple Ascending Dose Study in Subjects With Type 2 Diabetes
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
Study Type
Interventional
2. Study Status
Record Verification Date
November 2015
Overall Recruitment Status
Terminated
Why Stopped
This study was terminated on August 29th, 2014 due to a business decision by the Sponsor. The study was not terminated due to a safety reason.
Study Start Date
March 2013 (undefined)
Primary Completion Date
November 2014 (Actual)
Study Completion Date
March 2015 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Amgen
4. Oversight
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Diabetes Mellitus
Keywords
Type 2 diabetes
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
86 (Actual)
8. Arms, Groups, and Interventions
Arm Title
AMG 876
Arm Type
Active Comparator
Arm Title
Placebo
Arm Type
Placebo Comparator
Intervention Type
Drug
Intervention Name(s)
AMG 876
Intervention Description
Ascending multiple doses of study drug administered SC
Primary Outcome Measure Information:
Title
Subject incidence of treatment-emergent adverse events
Description
Physical examinations, vitals, laboratory analytes, and ECGs
Time Frame
43 Days (Cohorts 1, 3, 5 and 7), 57 Days (Cohorts 2, 4, 6 and 9) or 71 Days (Cohort 8).
Title
Subject incidence of anti-AMG 876 antibodies
Description
Laboratory analytes
Time Frame
43 Days (Cohorts 1, 3, 5 and 7), 57 Days (Cohorts 2, 4, 6 and 9) or 71 Days (Cohort 8).
Secondary Outcome Measure Information:
Title
AMG 876 serum PK parameters
Description
Concentration-time profiles for AMG 876
Time Frame
43 Days (Cohorts 1, 3, 5 and 7), 57 Days (Cohorts 2, 4, 6 and 9) or 71 Days (Cohort 8).
Title
Pharmacodynamic parameters
Description
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)
Time Frame
43 Days (Cohorts 1, 3, 5 and 7), 57 Days (Cohorts 2, 4, 6 and 9) or 71 Days (Cohort 8).
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
MD
Organizational Affiliation
Amgen
Official's Role
Study Director
Facility Information:
Facility Name
Research Site
City
Chula Vista
State/Province
California
ZIP/Postal Code
91911
Country
United States
Facility Name
Research Site
City
Miramar
State/Province
Florida
ZIP/Postal Code
33025
Country
United States
Facility Name
Research Site
City
Overland Park
State/Province
Kansas
ZIP/Postal Code
66212
Country
United States
Facility Name
Research Site
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45255
Country
United States
Facility Name
Research Site
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78209
Country
United States
Facility Name
Research Site
City
Renton
State/Province
Washington
ZIP/Postal Code
98057
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
33205064
Citation
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.
Results Reference
derived
Links:
URL
http://www.amgentrials.com
Description
AmgenTrials clinical trials website
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Multiple Ascending Dose Study in Subjects With Type 2 Diabetes
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