Single and Multiple Ascending Dose Study of AMG 171 in Subjects With Obesity

Phase 1TerminatedNCT04199351

Amgen60 enrolled

Overview

To assess the safety and tolerability of AMG 171 as single or multiple doses in subjects with obesity

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

Conditions

Obesity

Interventions

AMG 171DRUG

2 SAD cohorts of 8 subjects per cohort randomized 3:1 in Part A; 1 cohort of 8 subjects 3:1 ratio in Part B; and 24 subjects enrolled into 1 of 3 cohorts with 8 subjects randomized to receive 2 to 3 consecutive doses (titration) 3:1 ratio in Part C.

PlaceboDRUG

AMG 171 placebo

Eligibility

Sex: ALLMin age: 18 YearsMax age: 65 Years

Medical Language ↔ Plain English

Inclusion Criteria * Males and females with ages between 18 and 65 years old, inclusive * Except for obesity, otherwise healthy * Body mass index (BMI) greater than or equal to 30.0 kg/m2 and less than or equal to 40.0 kg/m2 at screening * Other Inclusion criteria may apply Exclusion Criteria: * Currently receiving treatment in another investigational device or drug study * Women of childbearing potential * 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 * Other Exclusion criteria may apply

Locations (3)

Anaheim Clinical Trials

Anaheim, California, United States

Orange County Research Center

Tustin, California, United States

Clinical Pharmacology of Miami, LLC

Miami, Florida, United States

Outcomes

Primary Outcomes

Number of Participants Who Experienced Treatment-Emergent Adverse Events (TEAEs)

An adverse event (AE) was any untoward medical occurrence in a clinical study participant irrespective of a causal relationship with study treatment. A serious AE (SAE) was an AE meeting at least 1 of the following serious criteria: fatal, life-threatening, required in-patient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability; congenital anomaly/birth defect; other medically important serious event. Clinically significant changes from baseline in laboratory safety tests, vital sign assessments, and 12-lead electrocardiogram assessments were included as TEAEs.

Time frame: From first dose of IP to end of study, up to Day 207

Secondary Outcomes

Maximum Observed Serum Concentration (Cmax) for AMG 171: SAD Cohorts 1 and 1b

Serum concentrations of AMG 171 were determined using a validated assay. Noncompartmental analysis was performed for estimation of pharmacokinetic (PK) parameters. Concentrations below the lower limit of quantification (LLOQ) (50.0 ng/mL) were set to zero before data analysis.

Time frame: Cohorts 1 and 1b: pre-dose Day 1; 1, 2, 4, and 8 hours post-dose Day 1, Days 2 up to Day 120

Cmax for AMG 171: MAD Cohorts 2 - 5

Serum concentrations of AMG 171 were determined using a validated assay. Noncompartmental analysis was performed for estimation of PK parameters. Concentrations below the LLOQ (50.0 ng/mL) were set to zero before data analysis.

Time frame: Cohort 2: pre-dose Days 1, 15, 29, 43, 57, 71; post-dose Days 5 up to 207; Cohort 3: pre-dose Days 1, 15; post-dose Days 2 up to 85; Cohort 4: pre-dose Days 1, 15, 29; post-dose Days 2 up to 113; Cohort 5: pre-dose Days 1, 8; post-dose Days 2 up to 85

Time of Cmax (Tmax) for AMG 171: SAD Cohorts 1 and 1b

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

Time frame: Cohorts 1 and 1b: pre-dose Day 1; 1, 2, 4, and 8 hours post-dose Day 1, Days 2 up to Day 120

Tmax for AMG 171: MAD Cohorts 2 - 5

Area Under the Plasma Concentration-time Curve (AUC) From Time 0 to Infinity (AUCinf) for AMG 171: SAD Cohorts 1 and 1b

Time frame: Cohorts 1 and 1b: pre-dose Day 1; 1, 2, 4, and 8 hours post-dose Day 1, Days 2 up to Day 120

AUC From Time 0 to 14 Days (AUC0-14) for AMG 171: MAD Cohorts 2 - 4

AUC From Time 0 to 7 Days (AUC0-7) for AMG 171: MAD Cohort 5

Time frame: Cohort 5: pre-dose Days 1, 8; post-dose Days 2 up to 85

Number of Participants With Anti-AMG 171 Antibodies

Serum samples were tested for binding and neutralizing antibodies against human Growth Differentiation Factor 15. Participants with transiently positive for binding or neutralizing antibodies had a negative result at the participant's last time point tested. bAb = binding antibody; nAb = neutralizing antibody; +ve = positive; -ve = negative; BL = baseline.

Time frame: Cohorts 1 and 1b: Day 1 pre-dose, Days 15, 29, 120; Cohort 2: Days 1, 29, 57 pre-dose, Days 15, 85, 207; Cohort 3: Days 1, 15 pre-dose, Days 29, 57, 85; Cohort 4: Days 1, 15, 29 pre-dose, Days 43, 85, 113; Cohort 5: Days 1, 8 pre-dose, Days 29, 57, 85