Ascending Multiple Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Evolocumab (AMG 145) in Adults With Hyperlipidemia on Stable Doses of a Statin
|ClinicalTrials.gov Identifier: NCT01133522|
Recruitment Status : Completed
First Posted : May 31, 2010
Results First Posted : October 22, 2015
Last Update Posted : October 22, 2015
|Condition or disease||Intervention/treatment||Phase|
|Hyperlipidemia||Biological: Evolocumab Biological: Placebo||Phase 1|
Participants receiving low-to-moderate-dose statins were randomized in a 1:3 ratio to receive subcutaneous placebo or evolocumab and enrolled sequentially into one of 5 dose-escalation cohorts:
- Evolocumab 14 mg/placebo once weekly (QW) × 6 doses
- Evolocumab 35 mg/placebo once weekly (QW) × 6 doses
- Evolocumab 140 mg/placebo every 2 weeks (Q2W) × 3 doses
- Evolocumab 280 mg/placebo every 2 weeks (Q2W) × 3 doses
- Evolocumab 420 mg/placebo every 4 weeks (Q2W) × 2 doses.
Participants receiving high-dose statins were randomized 1:3 to receive subcutaneous placebo or evolocumab 140 mg every 2 weeks × 3 doses (Cohort 6).
Participants diagnosed with familial hypercholesterolemia (HeFH) were randomized 1:2 to receive subcutaneous placebo or evolocumab 140 mg every 2 weeks × 3 doses (Cohort 7).
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||60 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Official Title:||A Phase 1, Randomized, Double-Blind, Placebo-Controlled, Ascending Multiple Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of AMG 145 in Subjects With Hyperlipidemia on Stable Doses of a Statin|
|Study Start Date :||June 2010|
|Primary Completion Date :||September 2011|
|Study Completion Date :||September 2011|
Participants received one of 5 dose levels of evolocumab administered as multiple subcutaneous doses.
Administered by subcutaneous injection
Placebo Comparator: Placebo
Participants received matching placebo dose regimens by subcutaneous injection.
Administered by subcutaneous injection
- Number of Participants With Adverse Events [ Time Frame: From the first dose of study drug until Day 85 ]
The relationship of each adverse event to the investigational product was assessed by the investigator.
A serious adverse event (SAE) is defined as an adverse event that
- is fatal
- is life threatening (places the subject at immediate risk of death)
- requires in-patient hospitalization or prolongation of existing hospitalization
- results in persistent or significant disability/incapacity
- is a congenital anomaly/birth defect
- other significant medical hazard.
- Number of Participants With Anti-Evolocumab Antibodies [ Time Frame: From the first dose of study drug until Day 85 ]Serum samples were analyzed by an electrochemiluminescence (ECL)-based immunoassay for anti-evolocumab binding antibodies. Positive samples were subsequently tested in a receptor-ligand binding bioassay for anti-evolocumab neutralizing antibodies
- Maximum Observed Plasma Concentration (Cmax) of Evolocumab [ Time Frame: Day 1, predose and Days 4, 8, 15, 22, 29, 36, 40, 43, 50, 57, 64, 71, 78, and 85 ]Serum concentrations of evolocumab were measured by a validated enzyme-linked immunosorbent assay (ELISA). The lower limit of quantification (LLOQ) was 800 ng/mL.
- Area Under the Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of Evolocumab [ Time Frame: Day 29 predose (last dose for Cohorts 3-7) and Days 36 (predose for Cohorts 1 and 2), 40, 43, 50, 57, 64, 71, 78, and 85 ]Area under the unbound evolocumab serum concentration-time curve from time of last dose to time of last quantifiable concentration following the last dose of evolocumab.
- Percent Change From Baseline to End of the Dosing Interval in LDL-C [ Time Frame: Baseline and Day 43 for QW and Q2W groups or Day 57 for Q4W group ]
- Percent Change From Baseline to End of the Dosing Interval in PCSK9 [ Time Frame: Baseline and Day 43 for QW and Q2W groups or Day 57 for Q4W group ]Serum PCSK9 concentrations were determined by using a qualified enzyme-linked immunosorbent assay (ELISA). The lower limit of quantification (LLOQ) was 15 ng/mL.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01133522