Multiple Ascending Dose Study in Subjects With Type 2 Diabetes

NCT01856881 | Terminated Phase 1

• 1 other identifier: 20100018
• Study Type: interventional
• Target: 86
• Locations: 1 country
• Sites: 6

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.

Conditions

Diabetes Mellitus

Keywords

Type 2 diabetes

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (2)

• 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).

• Pharmacodynamic parameters

  43 Days (Cohorts 1, 3, 5 and 7), 57 Days (Cohorts 2, 4, 6 and 9) or 71 Days (Cohort 8).

Study Arms (2)

AMG 876

ACTIVE COMPARATOR

Drug: AMG 876

Placebo

PLACEBO COMPARATOR

Drug: AMG 876

Interventions

AMG 876 DRUG

Ascending multiple doses of study drug administered SC

AMG 876; Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Amgen: lead

Study Sites (6)

Research Site

Chula Vista, California, 91911, United States

Location

Research Site

Miramar, Florida, 33025, United States

Location

Research Site

Overland Park, Kansas, 66212, United States

Location

Research Site

Cincinnati, Ohio, 45255, United States

Location

Research Site

San Antonio, Texas, 78209, United States

Location

Research Site

Renton, Washington, 98057, United States

Location

Related Publications (1)

• 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.

  PMID: 33205064 DERIVED

Related Links

• AmgenTrials clinical trials website

MeSH Terms

Conditions

Diabetes Mellitus; Diabetes Mellitus, Type 2

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Study Officials

• MD

  Amgen

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 25, 2013
• First Posted: May 20, 2013
• Study Start: March 1, 2013
• Primary Completion: November 1, 2014
• Study Completion: March 1, 2015
• Last Updated: November 6, 2015

Record last verified: 2015-11

Locations

US (6)