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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

About this trial

This is an interventional treatment trial for Diabetes Mellitus focused on measuring Type 2 diabetes

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

NCT ID

NCT01856881

First Posted

March 25, 2013

Last Updated

November 5, 2015

Sponsor

Amgen

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

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

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

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

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

Learn more about this trial

Multiple Ascending Dose Study in Subjects With Type 2 Diabetes

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