Clinical trial NCT01856881: 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
Overall status: TERMINATED
Phase: PHASE1
Conditions: Diabetes Mellitus
Keywords: Type 2 diabetes
Lead sponsor: Amgen
Sponsor class: INDUSTRY
First posted: 2013-05-20
Enrollment: 86
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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)

Primary outcomes:
measure: Subject incidence of treatment-emergent adverse events
timeFrame: 43 Days (Cohorts 1, 3, 5 and 7), 57 Days (Cohorts 2, 4, 6 and 9) or 71 Days (Cohort 8).
measure: Subject incidence of anti-AMG 876 antibodies
timeFrame: 43 Days (Cohorts 1, 3, 5 and 7), 57 Days (Cohorts 2, 4, 6 and 9) or 71 Days (Cohort 8).
Secondary outcomes:
measure: AMG 876 serum PK parameters
timeFrame: 43 Days (Cohorts 1, 3, 5 and 7), 57 Days (Cohorts 2, 4, 6 and 9) or 71 Days (Cohort 8).
measure: Pharmacodynamic parameters
timeFrame: 43 Days (Cohorts 1, 3, 5 and 7), 57 Days (Cohorts 2, 4, 6 and 9) or 71 Days (Cohort 8).
Other outcomes:
Locations:
city: Chula Vista
country: United States
facility: Research Site
state: California
city: Miramar
country: United States
facility: Research Site
state: Florida
city: Overland Park
country: United States
facility: Research Site
state: Kansas
city: Cincinnati
country: United States
facility: Research Site
state: Ohio
city: San Antonio
country: United States
facility: Research Site
state: Texas
city: Renton
country: United States
facility: Research Site
state: Washington
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References:
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.