Single and Multiple Ascending Dose Study of AMG 171 in Subjects With Obesity
- Registration Number
- NCT04199351
- Lead Sponsor
- Amgen
- Brief Summary
To assess the safety and tolerability of AMG 171 as single or multiple doses in subjects with obesity
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 60
Not provided
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Part B Placebo AMG 171 or placebo, 1 MAD cohort Part C Placebo AMG 171 or placebo, 3 titration cohorts Part A Placebo AMG 171 or placebo, 2 SAD cohorts Part C AMG 171 AMG 171 or placebo, 3 titration cohorts Part B AMG 171 AMG 171 or placebo, 1 MAD cohort Part A AMG 171 AMG 171 or placebo, 2 SAD cohorts
- Primary Outcome Measures
Name Time Method Number of Participants Who Experienced Treatment-Emergent Adverse Events (TEAEs) From first dose of IP to end of study, up to Day 207 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.
- Secondary Outcome Measures
Name Time Method Maximum Observed Serum Concentration (Cmax) for AMG 171: SAD Cohorts 1 and 1b Cohorts 1 and 1b: pre-dose Day 1; 1, 2, 4, and 8 hours post-dose Day 1, Days 2 up to Day 120 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.
Cmax for AMG 171: MAD Cohorts 2 - 5 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 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 of Cmax (Tmax) for AMG 171: SAD Cohorts 1 and 1b Cohorts 1 and 1b: pre-dose Day 1; 1, 2, 4, and 8 hours post-dose Day 1, Days 2 up to Day 120 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.
Tmax for AMG 171: MAD Cohorts 2 - 5 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 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.
Area Under the Plasma Concentration-time Curve (AUC) From Time 0 to Infinity (AUCinf) for AMG 171: SAD Cohorts 1 and 1b Cohorts 1 and 1b: pre-dose Day 1; 1, 2, 4, and 8 hours post-dose Day 1, Days 2 up to Day 120 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.
AUC From Time 0 to 14 Days (AUC0-14) for AMG 171: MAD Cohorts 2 - 4 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 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.
AUC From Time 0 to 7 Days (AUC0-7) for AMG 171: MAD Cohort 5 Cohort 5: pre-dose Days 1, 8; post-dose Days 2 up to 85 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.
Number of Participants With Anti-AMG 171 Antibodies 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 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.
Trial Locations
- Locations (3)
Anaheim Clinical Trials
🇺🇸Anaheim, California, United States
Clinical Pharmacology of Miami, LLC
🇺🇸Miami, Florida, United States
Orange County Research Center
🇺🇸Tustin, California, United States