A study of AMG 133 in adults with obesity or overweight, with or without type 2 diabetes

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 570

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 < 6.5% (< 48 mmol/mol) at screening without a diagnosis of type 1 or 2 diabetes mellitus.
- For subjects in cohort B only, HbA1c = 7% and = 10% (53 to 86 mmol/mol) at screening with an established diagnosis of type 2 diabetes mellitus for = 180 days prior to screening.
- For subjects in cohort B only, either treated with diet and exercise alone or on stable (at least 90 days prior to screening) treatment with metformin, a sulfonylurea, or a sodium-glucose cotransporter 2 (SGLT2) inhibitor as monotherapy or combination therapy, per approved local label.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 560
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 10

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 < 0.4 mIU/L as measured by central laboratory at screening. Subjects who received treatment for hypothyroidism are permitted in the study, if their thyroid hormone replacement dose has been stable for at least 90 days and their TSH at screening is within the above range.
•Obesity induced by other endocrine disorders (eg, Cushing syndrome).
•History of severe or symptomatic gastroparesis.
•A corrected QT interval (QTc) of > 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 < 30 ml/min/1.73 m2 estimated according to chronic kidney disease epidemiology collaboration [CKD-EPI] equation.
ii.Aspartate aminotransaminase (AST) or alanine aminotransaminase (ALT): = 2.5 times the upper limit of normal (ULN).
iii.Other laboratory abnormalities that may affect the completion or evaluation of the study, as judged by the investigator.
•Calcitonin = 50 ng/L (pg/mL) at screening.
•Lifetime history of acute or chronic pancreatitis, or elevation in serum lipase/amylase (> 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

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method

Secondary Outcome Measures

Name	Time	Method

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