Phase 1
Completed N=68
Safety And Tolerability Of Multiple Doses Of PF-04950615 (RN316) In Subjects With Hypercholesterolemia
Source: ClinicalTrials.gov NCT01243151 ↗Enrolled (actual)
68
Serious AEs
1.5%
Results posted
Jan 2019
Primary outcomePrimary: Number of Participants With Dose Limiting and Intolerable Treatment-Related Adverse Events (AEs) — 0; 0; 0; 0 participants
Summary
The primary objective of this study is to evaluate the safety and tolerability of repeated doses of PF-04950615 (RN316) in study volunteers with hypercholesterolemia. PF-04950615 is an investigational drug that is currently being studied as a lipid lowering agent.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Participants With Dose Limiting and Intolerable Treatment-Related Adverse Events (AEs) |
0; 0; 0; 0; 0; 0 | — |
| PRIMARY Number of Participants With Treatment-Emergent Adverse Events (AEs), Serious Adverse Events (SAEs) and Treatment-Related Adverse Events (AEs) |
9; 8; 5; 7; 9; 0 | — |
| PRIMARY Number of Participants With Adverse Events (AEs) by Severity |
8; 7; 5; 5; 6; 1 | — |
| PRIMARY Number of Participants With Laboratory Test Abnormalities |
7; 10; 2; 7; 7 | — |
| PRIMARY Number of Participants With Clinically Relevant Changes in Vital Signs |
1; 0; 0; 0; 0; 4 | — |
| PRIMARY Number of Participants With Clinically Relevant Changes in Electrocardiogram (ECG) Parameters |
1; 0; 0; 0; 0; 0 | — |
| PRIMARY Number of Participants With Anti-drug Antibodies (ADA) |
0; 1; 1; 2 | — |
| SECONDARY Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of PF-04950615 |
596700; 1224000; 2697000; 4253000; 749800; 2134000 | — |
| SECONDARY Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-04950615 |
6.00; 3.61; 1.00; 1.00; 6.00; 1.30 | — |
| SECONDARY Maximum Observed Plasma Concentration (Cmax) of PF-04950615 |
8077; 15080; 31380; 45110; 10170; 23680 | — |
| SECONDARY Plasma Decay Half-Life (t1/2) of PF-04950615 |
50.39; 71.50; 94.24; 140.4; 155.6; 247.2 | — |
| SECONDARY Apparent Clearance (CL) of PF-04950615 |
28.98; 18.26; 17.59; 14.05 | — |
| SECONDARY Volume of Distribution at Steady State (Vss) of PF-04950615 |
3815; 3221; 4035; 5285 | — |
| SECONDARY Accumulation Ratio (Rac) of PF-04950615 |
1.261; 1.685; 1.771; 1.964 | — |
| SECONDARY Change From Baseline in Low Density Lipoprotein Cholesterol (LDL-C) at Day 8, 15, 22, 29 and 78 |
160.96; 155.04; 160.39; 155.62; 164.00; -6.59 | <0.0001 sig |
| SECONDARY Percent Change From Baseline in Low Density Lipoprotein Cholesterol (LDL-C) at Day 8, 15, 22, 29 and 78 |
-4.15; -38.53; -31.59; -44.24; -40.72; -4.39 | <0.0001 sig |
| SECONDARY Number of Participants Achieving LDL-C Less Than (<) 70 Milligram Per Deciliter (mg/dL) |
0; 6; 3; 7; 8; 0 | 0.0472 sig |
| SECONDARY Number of Participants Achieving LDL-C Less Than (<) 100 Milligram Per Deciliter (mg/dL) |
0; 13; 10; 11; 12; 0 | 0.0013 sig |
| SECONDARY Number of Participants With Greater Than or Equal to (>=) 50 Percent (%) Reduction in LDL-C From Baseline |
0; 0; 5; 8; 8 | 0.9580 |
| SECONDARY Change From Baseline in Lipid Parameters: Apolipoprotein A1 (ApoA1) at Day 8, 15, 22, 29 and 78 |
142.67; 144.43; 150.39; 143.46; 156.39; -4.00 | 0.2883 |
| SECONDARY Change From Baseline in Lipid Parameters: Apolipoprotein B (ApoB) at Day 8, 15, 22, 29 and 78 |
126.54; 124.04; 120.32; 125.62; 119.57; -7.79 | <0.0001 sig |
| SECONDARY Change From Baseline in Lipid Parameters: Total Cholesterol at Day 8, 15, 22, 29 and 78 |
237.75; 233.21; 239.36; 242.54; 247.21; -8.67 | <0.0001 sig |
| SECONDARY Change From Baseline in Lipid Parameters: High Density Lipoprotein Cholesterol (HDL-C) at Day 8, 15, 22, 29 and 78 |
46.29; 47.75; 52.89; 49.23; 55.64; -1.71 | 0.3064 |
| SECONDARY Change From Baseline In Lipid Parameters: Non High Density Lipoprotein Cholesterol (Non HDL-C) at Day 8, 15, 22, 29 and 78 |
191.46; 185.46; 186.46; 193.31; 191.57; -6.96 | <0.0001 sig |
| SECONDARY Change From Baseline In Lipid Parameters: Triglycerides (TG) at Day 8, 15, 22, 29 and 78 |
152.92; 152.00; 130.36; 182.27; 137.96; 4.33 | 0.4480 |
| SECONDARY Percent Change From Baseline in Lipid Parameters: Apolipoprotein A1 (ApoA1) at Day 8, 15, 22, 29 and 78 |
-2.15; 1.38; 0.55; -1.17; -0.19; -0.18 | 0.3326 |
| SECONDARY Percent Change From Baseline In Lipid Parameters: Apolipoprotein B (ApoB) at Day 8, 15, 22, 29 and 78 |
-5.78; -31.37; -27.78; -36.61; -34.71; -7.08 | <0.0001 sig |
| SECONDARY Percent Change From Baseline In Lipid Parameters: Total Cholesterol at Day 8, 15, 22, 29 and 78 |
-3.73; -26.43; -22.11; -31.68; -28.70; -4.46 | <0.0001 sig |
| SECONDARY Percent Change From Baseline In Lipid Parameters: High Density Lipoprotein Cholesterol (HDL-C) at Day 8, 15, 22, 29 and 78 |
-2.75; 1.26; 0.31; -2.64; 0.61; -3.98 | 0.2690 |
| SECONDARY Percent Change From Baseline In Lipid Parameters: Non High Density Lipoprotein Cholesterol (Non HDL-C) at Day 8, 15, 22, 29 and 78 |
-3.85; -33.32; -28.56; -39.11; -36.85; -4.33 | <0.0001 sig |
| SECONDARY Percent Change From Baseline In Lipid Parameters: Triglycerides (TG) at Day 8, 15, 22, 29 and 78 |
-2.25; 0.47; -9.47; -15.52; -1.90; -1.76 | 0.9789 |
| SECONDARY Change From Baseline In Low Density Lipoprotein Cholesterol (LDL-C) Particle Size at Day 8, 15, 22, 36, 50, 64 and 78 |
20.37; 20.48; 21.04; 20.66; 21.18; 0.00 | — |
| SECONDARY Change From Baseline In Small Low Density Lipoprotein Cholesterol (LDL-C) Particle Levels at Day 8, 15, 22, 36, 50, 64 and 78 |
1436.42; 1285.21; 982.14; 1163.69; 870.07; -104.67 | — |
| SECONDARY Change From Baseline In Medium Low Density Lipoprotein Cholesterol (LDL-C) Particle Levels at Day 8, 15, 22, 36, 50, 64 and 78 |
302.67; 257.57; 196.57; 237.31; 171.14; -45.33 | — |
| SECONDARY Change From Baseline In Large Low Density Lipoprotein Cholesterol (LDL-C) Particle Levels at Day 8, 15, 22, 36, 50, 64 and 78 |
367.42; 424.71; 578.57; 459.00; 639.36; 16.42 | — |
| SECONDARY Change From Baseline In Total Low Density Lipoprotein Cholesterol (LDL-C) Particle Levels at Day 8, 15, 22, 36, 50, 64 and 78 |
1898.83; 1789.29; 1626.14; 1694.15; 1549.71; -100.42 | — |
| SECONDARY Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) Levels at Baseline, Day 8, 15, 22, 36, 50, 64 and 78 |
48.83; 43.96; 43.07; 34.10; 44.12; 48.53 | — |
| SECONDARY C-Reactive Protein Levels at Day 8, 15, 21, 36, 57 and 78 |
0.23; 0.26; 0.18; 0.42; 0.16; 0.30 | — |
| SECONDARY Small High Density Lipoprotein-Cholesterol (HDL-C) Particle Levels at Day 8, 15, 22, 36, 50, 64 and 78 |
23.26; 22.79; 20.64; 19.74; 21.49; 23.13 | — |
| SECONDARY Medium High Density Lipoprotein-Cholesterol (HDL-C) Particle Levels at Day 8, 15, 22, 36, 50, 64 and 78 |
1.90; 4.24; 5.12; 6.24; 5.29; 2.80 | — |
| SECONDARY Large High Density Lipoprotein-Cholesterol (HDL-C) Particle Levels at Day 8, 15, 22, 36, 50, 64 and 78 |
5.88; 6.81; 7.97; 6.87; 8.08; 5.90 | — |
| SECONDARY Total High Density Lipoprotein-Cholesterol (HDL-C) Particle Levels at Day 8, 15, 22, 36, 50, 64 and 78 |
31.07; 33.84; 33.72; 32.85; 34.83; 31.83 | — |
| SECONDARY Small Very Low Density Lipoprotein-Cholesterol (VLDL-C) Particle Levels at Day 8, 15, 22, 36, 50, 64 and 78 |
48.02; 38.97; 36.84; 36.69; 28.94; 54.04 | — |
| SECONDARY Medium Very Low Density Lipoprotein-Cholesterol (VLDL-C) Particle Levels at Day 8, 15, 22, 36, 50, 64 and 78 |
43.84; 31.89; 21.82; 32.02; 34.56; 45.18 | — |
| SECONDARY Large Very Low Density Lipoprotein-Cholesterol (VLDL-C) Particle Levels at Day 8, 15, 22, 36, 50, 64 and 78 |
4.66; 3.91; 2.43; 5.18; 4.63; 2.84 | — |
| SECONDARY Total Very Low Density Lipoprotein-Cholesterol (VLDL-C) Particle Levels at Day 8, 15, 22, 36, 50, 64 and 78 |
96.56; 74.79; 61.11; 73.92; 68.14; 102.08 | — |
| SECONDARY High Density Lipoprotein-Cholesterol (HDL-C) Particle Size at Day 8, 15, 22, 36, 50, 64 and 78 |
8.73; 8.81; 9.02; 8.88; 9.01; 8.72 | — |
| SECONDARY Very Low Density Lipoprotein-Cholesterol (VLDL-C) Particle Size at Day 8, 15, 22, 36, 50, 64 and 78 |
48.57; 51.21; 50.15; 51.37; 50.07; 48.13 | — |
Eligibility Criteria
Inclusion Criteria
- LDL-C must be greater or equal to 130 mg/dl
- BMI must be between 18.5 and 40 kg/m2
- Japanese volunteers must have 4 Japanese grand parents born in Japan
Exclusion Criteria
- History of cardiovascular or cerebrovascular event during the past year.
- Poorly controlled type 1 or type 2 diabetes mellitus
- Subjects who have taken lipid lowering therapies within the last 3 months of screening.
Data sourced from ClinicalTrials.gov (NCT01243151). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.