CER-001 is well tolerated when administered to humans as single doses up to 45 mg/kg. |
CER-001 mobilises cholesterol and increases its elimination via reverse lipid transport. |
CER-001 inhibits atherosclerotic plaque progression, providing considerable optimism that it may address the residual risk of cardiovascular events that remains after maximum clinical benefit has been achieved using low-density lipoprotein-cholesterol-lowering therapies. |
1 Introduction
2 Methods
2.1 Key Preclinical Pharmacology Studies
2.1.1 Cholesterol Mobilisation
2.1.2 Attenuated Inhibition of Atherosclerotic Plaque Progression
2.2 Phase I Single Rising-Dose Clinical Study
3 Results
3.1 Key Preclinical Pharmacology Studies
3.1.1 Cholesterol Mobilisation
Measure/time (h) | CER-001 (mg/kg) | ||||
---|---|---|---|---|---|
Placebo | 2.5 | 5.0 | 10.0 | 20.0 | |
Total cholesterol | |||||
30 | −0.286 | −0.137 | 0.047 | −0.029 | 0.046 |
34 | −0.274 | −0.149 | 0.017 | −0.173 | −0.090 |
Free cholesterol | |||||
30 | −0.038 | −0.007 | 0.039 | 0.086 | 0.068 |
34 | −0.049 | −0.023 | 0.006 | −0.005 | −0.001 |
Cholesterol ester | |||||
30 | −0.248 | −0.130 | 0.008 | −0.115 | −0.022 |
34 | −0.225 | −0.126 | 0.011 | −0.168 | −0.089 |
3.1.2 Attenuated Inhibition of Atherosclerotic Plaque Progression
3.2 Phase I Single Rising-Dose Clinical Study
CER-001 (mg/kg) | ||||||||
---|---|---|---|---|---|---|---|---|
0.25 (n = 4) | 0.75 (n = 4) | 2 (n = 4) | 5 (n = 4) | 10 (n = 4) | 15 (n = 4) | 30 (n = 4) | 45 (n = 4) | |
Age, years | ||||||||
Mean (SD) | 28.8 (8.4) | 40.8 (7.6) | 30.0 (8.8) | 29.0 (8.4) | 32.8 (11.2) | 33.8 (4.0) | 35.0 (12.1) | 39.3 (11.9) |
Median (range) | 26.0 (22–41) | 39.5 (33–51) | 28.5 (22–41) | 27.0 (22–40) | 31.0 (21–48) | 35.0 (28–37) | 38.5 (18–45) | 41.0 (24–51) |
Male/female, n (%) | 4/0 (100/0) | 4/0 (100/0) | 3/1 (75/25) | 4/0 (100/0) | 3/1 (75/25) | 4/0 (100/0) | 4/0 (100/0) | 4/0 (100/0) |
White/Black or African-American, n (%) | 4/0 (100/0) | 4/0 (100/0) | 3/1 (75/25) | 3/1 (75/25) | 4/0 (100/0) | 2/2 (50/50) | 4/0 (100/0) | 4/0 (100/0) |
AE | CER-001 (mg/kg) | |||||||||
---|---|---|---|---|---|---|---|---|---|---|
0.25 (n = 4) | 0.75 (n = 4) | 2 (n = 4) | 5 (n = 4) | 10 (n = 4) | 15 (n = 4) | 30 (n = 4) | 45 (n = 4) | All doses (n = 32) | Placebo (n = 32) | |
No. of AEs | 0 | 1 | 0 | 0 | 0 | 1 | 1 | 1 | 4 | 4 |
No. of subjects with an AE (%) | 0 | 1 (25) | 0 | 0 | 0 | 1 (25) | 1 (25) | 1 (25) | 4 (13) | 3 (9) |
Abdominal pain | 0 | 0 | 0 | 0 | 0 | 0 | 1 (25) | 0 | 1 (3) | 0 |
Diarrhoea | 0 | 0 | 0 | 0 | 0 | 1 (25) | 0 | 0 | 1 (3) | 0 |
Hordeolum | 0 | 1 (25) | 0 | 0 | 0 | 0 | 0 | 1 (3) | 0 | |
Nasopharyngitis | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 (3) |
Limb injury | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 (25) | 1 (3) | 0 |
Presyncope | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 (3) |
Cough | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 (3) |
Oropharyngeal pain | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 (3) |