Overweight and Obesity MedDRA version: 20.0 Level: PT Classification code 10029883 Term: Obesity System Organ Class: 10027433 - Metabolism and nutrition disorders MedDRA version: 24.1 Level: PT Classification code 10033307 Term: Overweight System Organ Class: 10027433 - Metabolism and nutrition disorders
Conditions
Interventions
Product Code: AMG 133
Pharmaceutical Form: Solution for injection
INN or Proposed INN: Pending
Other descriptive name: AMG 133
Concentration unit: mg milligram(s)
Concentration type: equal
Concentrati
Sponsors
Amgen Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Subjects are eligible to be included in the study only if all of the following criteria apply: - The subject has provided informed consent prior to initiation of any study-specific activities/procedures. - Age = 18 years (or = legal age within the country if it is older than 18 years). - Subject has a BMI = 27 kg/m2 at screening. - Subject has had at least 1 unsuccessful attempt at weight loss by diet and exercise in the opinion of the investigator. - For subjects in cohort A only, the presence of at least 1 of the following weight-related complications: hypertension, dyslipidemia, obstructive sleep apnea or cardiovascular disease; or BMI = 30 kg/m2. - For subjects in cohort A only, HbA1c =65 years) yes F.1.3.1 Number of subjects for this age range 10
Exclusion criteria
Exclusion criteria: Subjects are excluded from the study if any of the following criteria apply: Disease Related •Subjects with type 1 diabetes mellitus, history of ketoacidosis or hyperosmolar state/coma, or any other types of diabetes except type 2 diabetes mellitus (for cohort B only). •History of proliferative diabetic retinopathy, diabetic macular edema, or nonproliferative diabetic retinopathy that requires acute treatment. •For the subjects in the DEXA substudy only, body weight greater than the local DEXA scanner capacity at screening. •Change in body weight > 5 kg within 90 days before screening per subject report or medical records. •For subjects in cohort B only, fasting glucose > 270 mg/dL (15.0 mmol/L) at screening. Other Medical Conditions •Any of the following within the last 6 months prior to screening: myocardial infarction, unstable angina, coronary artery bypass graft, percutaneous coronary intervention (diagnostic angiograms are permitted), transient ischemic attack, cerebrovascular accident, or decompensated congestive heart failure; or currently have New York Health Association Class III or IV heart failure •Malignancy except nonmelanoma skin cancers, cervical or breast ductal carcinoma in situ within the last 5 years. •Uncontrolled thyroid disease, defined as TSH > 6.0 mIU/L or 450 msec in males or > 470 msec in females at screening as assessed by the investigator, or history of long QT syndrome. •Any of the following laboratory abnormalities at screening: i.An eGFR 2x ULN) at screening, or fasting serum triglyceride level of > 500 mg/dL at screening. •Personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia type 2. •History of major depressive disorder within 2 years before randomization. •Lifetime history of other severe psychiatric disorders (eg, schizophrenia, bipolar disorder). •A PHQ-9 score of = 15 at screening or day 1 before randomization. •Any lifetime history of a suicidal attempt. •Any suicidal behavior within 2 years before randomization. •Any suicidal ideation of type 4 or 5 on the C-SSRS at screening or day 1 before randomization. Prior/Concomitant Therapy •Treatment within 90 days before screening with any medication for obesity or that may cause significant weight change per the investigator’s judgment, including but not limited to: phentermine, topiramate, zonisamide, lorcaserin, bupropion, naltrexone, orlistat, diethylpropion, exenatide, liraglutide, dulaglutide, semaglutide, tirzepatide, setmelanotide, pramlintide, leptin, or SGLT2 inhibitors (except for cohort B). •Previous o
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To compare and assess the dose-response of 3 selected doses of AMG 133 compared with placebo, on inducing and maintaining weight loss from baseline at week 52 in subjects with overweight or obesity without diabetes mellitus (cohort A) and in subjects with overweight or obesity with diabetes mellitus (cohort B).;Secondary Objective: Key Secondary •To evaluate the effect of AMG 133 on achieving specific categories of body weight loss from baseline at week 52 in cohorts A and B •To evaluate the effect of AMG 133 on glucose metabolism in cohorts A and B •To characterize the pharmacokinetics (PK) properties of AMG 133 Secondary •To evaluate the effect of AMG 133 on waist circumference •To assess the treatment effect of dose-escalation regimens •To evaluate the effect of AMG 133 on systolic blood pressure (SBP) •To evaluate the effect of AMG 133 on diastolic blood pressure (DBP) •To evaluate the effect of AMG 133 on body composition (total fat mass, lean body mass, visceral fat mass) in a subpopulation •To evaluate the effect of AMG 133 on a markers of inflammation •To evaluate the effect of AMG 133 on body mass index (BMI) •To evaluate the effect of AMG 133 on lipid parameters;Primary end point(s): •Percent change from baseline to week 52 in body weight ;Timepoint(s) of evaluation of this end point: From baseline to week 52 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Key Secondary: • Achieving = 5% reduction in body weight from baseline at week 52 (yes/no) • Achieving = 10% reduction in body weight from baseline at week 52 (yes/no) • Achieving = 15% reduction in body weight from baseline at week 52 (yes/no) • Achieving = 20% reduction in body weight from baseline at week 52 (yes/no) • Change from baseline to week 52 in hemoglobin A1c (HbA1c) (%, mmol/mol) • Change from baseline to week 52 in fasting serum insulin • Change from baseline to week 52 in fasting plasma glucose • Change from baseline to week 52 in Homeostasis Model Assessment for insulin resistance (HOMA2-IR) • Change from baseline to week 52 in Homeostasis Model Assessment for steady state beta cell function (HOMA2-%B) • PK parameters for AMG 133 including, but not limited to maximum observed plasma concentration (Cmax), and area under the concentration-time curve (AUC) Secondary • Change from baseline to week 52 in waist circumference • Change from baseline to week 52 in body weight • Change from baseline to week 52 in SBP • Change from baseline to week 52 in DBP • Change from baseline to week 52 in (total and regional visceral) fat and lean body mass using dual energy X ray absorptiometry (DEXA) for a subset of subjects • Percent change from baseline in high-sensitivity C-reactive protein (hs-CRP) • Change from baseline to week 52 in BMI • Percent change from baseline to week 52 in low density lipoprotein cholesterol (LDL-C) • Percent change from baseline to week 52 in total cholesterol • Percent change from baseline to week 52 in high density lipoprotein cholesterol (HDL-C) • Percent change from baseline to week 52 in non-HDL-C • Percent change from baseline to week 52 in very low-density lipoprotein cholesterol (VLDL-C) • Percent change from baseline to week 52 in triglycerides • Percent change from baseline to week 52 in free fatty acids (FFA) ;Timepoint(s) of evaluation of this end point: From baseline to week 52 | — |
Countries
Australia, Canada, Czechia, Czech Republic, Germany, Hong Kong, Hungary, Japan, Korea, Republic of, Poland, Spain, Taiwan, United Kingdom, United States
Contacts
Public ContactMedical Information
Amgen Kft.
Outcome results
None listed