Multiple Ascending Dose Study of AMG 598 in Adults With Obesity

Obesity Clinical Trial

Official title:

A Phase 1b, Randomized, Double-blind, Placebo-controlled, Multiple Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of AMG 598 in Subjects With Obesity

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03757130
• Other study ID #: 20170139
• Status: Completed
• Phase: Phase 1
• Start date: November 26, 2018
• Est. completion date: December 16, 2019

Study information

• Verified date: November 2022
• Source: Amgen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The main objective of this study is to assess the safety and tolerability of multiple doses of AMG 598 administered alone or in combination with liraglutide in adults with obesity.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 50
• Est. completion date: December 16, 2019
• Est. primary completion date: December 16, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

• Men and women with ages between 18 and 65 years old, inclusive, at time of signing consent
• Body mass index (BMI) between greater than or equal to 30.0 kg/m^2 and less than or equal to 40.0 kg/m^2 at screening
• Except for obesity, otherwise healthy or medically stable per protocol
• Have a stable body weight defined as less than 5 kg self-reported change during the previous 8 weeks prior to screening
• Other Inclusion criteria may apply
• Stable on liraglutide, depending on cohort

Exclusion Criteria:

• History or clinical evidence of diabetes
• Inadequate organ function at screening
• Currently receiving treatment in another investigational device or drug study
• Women who are pregnant/lactating/breastfeeding or who plan to become pregnant/breastfeed while on study through 5 months after receiving the last dose of investigational product
• History or evidence of a clinically significant disorder, condition or disease that would pose a risk to subject safety or interfere with the study evaluation, procedures or completion
• A family or personal history of medullary thyroid carcinoma or multiple endocrine neoplasia type 2; a personal history of non-familial medullary thyroid carcinoma; confirmed chronic pancreatitis or idiopathic acute pancreatitis, or gallbladder disease (ie, cholelithiasis or cholecystitis) not treated with cholecystectomy, for cohorts receiving liraglutide
• History of major depressive disorder
• Other Exclusion criteria may apply

Related Conditions & MeSH terms

• Obesity

Intervention

Drug:
• AMG 598
AMG 598 administered by subcutaneous injection
• Placebo
Placebo matching to AMG 598 administered by subcutaneous injection
• Liraglutide
Liraglutide administered by subcutaneous injection. The starting dose is 0.6 mg/day, and increased by 0.6 mg/day dose increment every 7 days, up to the full dosage of 3.0 mg/day by week 5.

Locations

Country	Name	City	State
United States	William D Summers MD LLC	Birmingham	Alabama
United States	Dallas Diabetes and Endocrine Center	Dallas	Texas
United States	QPS Miami Research Associates	South Miami	Florida
United States	Orange County Research Center	Tustin	California

Sponsors (1)

Lead Sponsor	Collaborator
Amgen

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Treatment-emergent Adverse Events	The investigator assessed the severity of each adverse event reported during the study. The assessment was based on the Amgen Standard Grading Scale: Mild: Aware of sign or symptom, but easily tolerated. Moderate: Discomfort enough to cause interference with usual activity. Severe: Incapacitating with inability to work or do usual activity.; A Serious adverse event is defined as any untoward medical occurrence that, met at least 1 of the following serious criteria; Death; Was life-threatening; Required in-patient hospitalization or prolongation of existing hospitalization; Resulted in persistent or significant disability/incapacity; Was a congenital anomaly/birth defect; Other medically important serious event.; The investigator also assessed whether each adverse event was related to study drug administration based on clinical judgement.	207 days
Primary	Number of Participants With TEAEs Due to Laboratory, Electrocardiogram, and Vital Sign Findings	TEAEs due to laboratory, electrocardiogram (ECG) and vital sign findings include any abnormal laboratory test results (hematology, clinical chemistry, or urinalysis) or electrocardiogram, or vital signs measurements, including those that worsened from baseline, that were considered clinically significant in the medical and scientific judgment of the investigator (ie, not related to progression of underlying disease).	207 days
Secondary	Maximum Observed Concentration (Cmax) of AMG 598 After Subcutaneous Injection on Day 1 and Day 57	Serum concentrations of AMG 598 were determined using a validated electrochemiluminescence-based method. The lower limit of quantitation was 50.0 ng/mL.	Day 1, predose, and days 6, 8, 15, 22, and 29; Day 57 predose and days 62, 64, 71, 85, 99, 113, 127, 169, and 207
Secondary	Time to Maximum Observed Concentration (Tmax) of AMG 598 After Subcutaneous Injection on Day 1 and Day 57	Serum concentrations of AMG 598 were determined using a validated electrochemiluminescence-based method. The lower limit of quantitation was 50.0 ng/mL.	Day 1, predose, and days 6, 8, 15, 22, and 29; Day 57 predose and days 62, 64, 71, 85, 99, 113, 127, 169, and 207
Secondary	Dose-normalized Cmax of AMG 598 After Subcutaneous Injection on Day 1 and Day 57	Serum concentrations of AMG 598 were determined using a validated electrochemiluminescence-based method. The lower limit of quantitation was 50.0 ng/mL.	Day 1, predose, and days 6, 8, 15, 22, and 29; Day 57 predose and days 62, 64, 71, 85, 99, 113, 127, 169, and 207
Secondary	Area Under the Concentration-time Curve From Time 0 to 28 Days (AUC0-28) for AMG 598 After Subcutaneous Injection on Day 1 and Day 57	Serum concentrations of AMG 598 were determined using a validated electrochemiluminescence-based method. The lower limit of quantitation was 50.0 ng/mL.	Day 1, predose, and days 6, 8, 15, 22, and 29; Day 57 predose and days 62, 64, 71, and 85
Secondary	Dose-normalized AUC0-28 for AMG 598 After Subcutaneous Injection on Day 1 and Day 57	Serum concentrations of AMG 598 were determined using a validated electrochemiluminescence-based method. The lower limit of quantitation was 50.0 ng/mL.	Day 1, predose, and days 6, 8, 15, 22, and 29; Day 57 predose and days 62, 64, 71, and 85
Secondary	Area Under the Concentration-time Curve From Time 0 to Time of Last Quantifiable Concentration (AUClast) of AMG 598 After Subcutaneous Injection on Day 57	Serum concentrations of AMG 598 were determined using a validated electrochemiluminescence-based method. The lower limit of quantitation was 50.0 ng/mL.	Day 57 predose and days 62, 64, 71, 85, 99, 113, 127, 169, and 207
Secondary	Accumulation Ratio (AR) for Cmax of AMG 598 After Subcutaneous Injection on Day 1 and Day 57	Serum concentrations of AMG 598 were determined using a validated electrochemiluminescence-based method. The lower limit of quantitation was 50.0 ng/mL.; Accumulation ratio for Cmax = Day 57 Cmax / Day 1 Cmax.	Day 1, predose, and days 6, 8, 15, 22, and 29; Day 57 predose and days 62, 64, 71, 85, 99, 113, 127, 169, and 207
Secondary	Accumulation Ratio of AUC0-28 for AMG 598 After Subcutaneous Injection on Day 1 and Day 57	Serum concentrations of AMG 598 were determined using a validated electrochemiluminescence-based method. The lower limit of quantitation was 50.0 ng/mL.; The accumulation ratio for AUC0-28 = Day 57 AUC0-28 / Day 1 AUC0-28.	Day 1, predose, and days 6, 8, 15, 22, and 29; Day 57 predose and days 62, 64, 71, and 85
Secondary	Terminal Half-life (T1/2,z) of AMG 598 After Subcutaneous Injection on Day 57	Serum concentrations of AMG 598 were determined using a validated electrochemiluminescence-based method. The lower limit of quantitation was 50.0 ng/mL.	Day 57 predose and days 62, 64, 71, 85, 99, 113, 127, 169, and 207

External Links

•   AmgenTrials clinical trials website