Phase 1
Completed N=25
Pharmacokinetic And Pharmacodynamic Study Of A Single-Dose Of PF-04950615 (RN316) In Combination With Atorvastatin
Source: ClinicalTrials.gov NCT01163851 ↗Enrolled (actual)
25
Serious AEs
4.2%
Results posted
May 2015
Primary outcomePrimary: Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of PF-04950615 — 17950000; 933800 nanogram*hour per milliliter
Summary
The primary objective of this study is to evaluate the pharmacokinetics and pharmacodynamics of a single dose of PF-04950615 (RN316) in volunteers on stable doses of atorvastatin. PF-04950615 (RN316) is an investigational drug that is currently being studies as a cholesterol lowering therapy.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of PF-04950615 |
17950000; 933800 | — |
| PRIMARY Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-04950615 |
2.59; 4.00 | — |
| PRIMARY Maximum Observed Plasma Concentration (Cmax) of PF-04950615 |
105000; 14030 | — |
| PRIMARY Plasma Decay Half-Life (t1/2) of PF-04950615 |
157.50; 61.00 | — |
| PRIMARY Systemic Clearance (CL) of PF-04950615 |
0.0185; 0.0392 | — |
| PRIMARY Volume of Distribution at Steady State (Vss) of PF-04950615 |
4.248; 3.436 | — |
| PRIMARY Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUC0-inf) of PF-04950615 |
17960000; 1094000 | — |
| PRIMARY Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of Atorvastatin |
71.73; 89.17 | — |
| PRIMARY Time to Reach Maximum Observed Plasma Concentration (Tmax) of Atorvastatin |
1.16; 1.00 | — |
| PRIMARY Maximum Observed Plasma Concentration (Cmax) of Atorvastatin |
15.79; 20.68 | — |
| PRIMARY Plasma Decay Half-Life (t1/2) of Atorvastatin |
5.12; 5.09 | — |
| PRIMARY Apparent Oral Clearance (CL/F) of Atorvastatin |
557.50; 448.70 | — |
| PRIMARY Apparent Volume of Distribution (Vz/F) of Atorvastatin |
3950; 3353 | — |
| SECONDARY Change From Baseline in Fasting Low Density Lipoprotein-Cholesterol (LDL-C) at Day 5, 6, 7, 15, 22, 29, 36, 43, 50, 57 and 64 |
-14.30; -16.2; -28.50; -34.00; -33.30; -47.20 | — |
| SECONDARY Change From Baseline in Fasting Total Cholesterol at Day 5, 6, 7, 15, 22, 29, 36, 43, 50, 57 and 64 |
-13.90; -21.60; -33.30; -38.30; -37.30; -50.00 | — |
| SECONDARY Change From Baseline in Fasting Non High-density Lipoprotein-Cholesterol (Non-HDL-C) at Day 5, 6, 7, 15, 22, 29, 36, 43, 50, 57 and 64 |
12.60; -19.40; -31.20; -35.90; -36.40; -47.60 | — |
| SECONDARY Change From Baseline in Fasting Triglycerides at Day 5, 6, 7, 15, 22, 29, 36, 43, 50, 57 and 64 |
9.20; -15.80; 11.70; -9.90; 8.10; -6.90 | — |
| SECONDARY Change From Baseline in Fasting Apolipoprotein B (ApoB) at Day 5, 6, 7, 15, 22, 29, 36, 43, 50, 57 and 64 |
-10.90; -13.10; -22.10; -24.90; -28.30; -29.50 | — |
| SECONDARY Change From Baseline in Fasting Apolipoprotein A1 (ApoA1) at Day 5, 6, 7, 15, 22, 29, 36, 43, 50, 57 and 64 |
-3.00; 2.80; -1.70; -5.60; 3.40; -1.50 | — |
| SECONDARY Change From Baseline in Fasting High-Density Lipoprotein (HDL) Cholesterol at Day 5, 6, 7, 15, 22, 29, 36, 43, 50, 57 and 64 |
-1.30; -2.20; -2.10; -2.40; -0.90; -2.40 | — |
| SECONDARY Percent Change From Baseline in Fasting Low Density Lipoprotein-Cholesterol (LDL-C) at Day 5, 6, 7, 15, 22, 29, 36, 43, 50, 57 and 64 |
-15.70; -27.30; -33.80; -47.00; -38.90; -65.10 | — |
| SECONDARY Percent Change From Baseline in Total Cholesterol at Day 5, 6, 7, 15, 22, 29, 36, 43, 50, 57 and 64 |
-8.30; -14.60; -21.20; -26.20; -23.10; -34.10 | — |
| SECONDARY Percent Change From Baseline in Fasting Non-High-density Lipoprotein-cholesterol (Non-HDL-C) at Day 5, 6, 7, 15, 22, 29, 36, 43, 50, 57 and 64 |
-9.90; -20.30; -28.70; -37.60; -32.80; -50.00 | — |
| SECONDARY Percent Change From Baseline in Fasting Triglycerides Values at Day 5, 6, 7, 15, 22, 29, 36, 43, 50, 57 and 64 |
11.20; -3.30; 7.40; 1.10; 5.00; 0.50 | — |
| SECONDARY Percent Change From Baseline in Fasting Apolipoprotein B (ApoB) Values at Day 5, 6, 7, 15, 22, 29, 36, 43, 50, 57 and 64 |
-13.50; -17.10; -26.90; -31.10; -33.80; -36.10 | — |
| SECONDARY Percent Change From Baseline in Fasting High-Density Lipoprotein (HDL) Cholesterol Values at Day 5, 6, 7, 15, 22, 29, 36, 43, 50, 57 and 64 |
-2.50; -1.70; -3.60; -0.90; -1.10; -0.90 | — |
| SECONDARY Percent Change From Baseline in Fasting Apolipoprotein A1 (ApoA1) Values at Day 5, 6, 7, 15, 22, 29, 36, 43, 50, 57 and 64 |
-1.90; 2.10; -1.00; -4.20; 2.90; -0.80 | — |
| SECONDARY Duration of Low Density Lipoprotein (LDL) Lowering Effects |
48.5; 18.0 | — |
| SECONDARY Number of Participants With Toxicity or Intolerable Dose Criteria |
0; 0 | — |
| SECONDARY Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) |
12; 11; 1; 0 | — |
| SECONDARY Number of Participants With Treatment-Emergent Adverse Events by Severity |
5; 8; 4; 3; 2; 0 | — |
| SECONDARY Number of Participants With Treatment-Related Adverse Events (AEs) and Serious Adverse Events (SAEs) |
6; 0; 0; 0 | — |
| SECONDARY Number of Participants With Systemic Treatment Emergent Adverse Events Identified by Physical Examination |
0; 0 | — |
| SECONDARY Number of Participants With Systemic Treatment Emergent Adverse Events Identified by Vital Signs |
0; 2; 0; 0; 0; 1 | — |
| SECONDARY Number of Participants With Systemic Treatment Emergent Adverse Events Identified by Electrocardiogram (ECG) Parameters |
0; 1; 0; 0; 0; 1 | — |
| SECONDARY Number of Participants With Systemic Treatment Emergent Adverse Events Identified by Laboratory Parameters |
2; 1; 2; 0; 0; 1 | — |
| SECONDARY Number of Participants With Positive Anti-drug Antibodies (ADA) |
4; 0 | — |
Eligibility Criteria
Inclusion Criteria
- On stable doses of atorvastatin (40 mg daily) for 45 days prior to Day 1.
- BMI 18.5 to 40 kg/m2 inclusive, and body weight equal or lower than 150 kg.
Exclusion Criteria
- History of a cardiovascular event (e.g., MI ) during the past year.
- Poorly controlled Type 1 or Type 2 Diabetes mellitus (definition: uncontrolled diabetes is defined as HBIAc >9%).
- Poorly controlled hypertension (uncontrolled hypertension is defined as a systolic blood pressure greater than 140 mm Hg or a diastolic blood pressure greater than 90 mm Hg, even with treatment). Subjects who have hypertension and are controlled on stable dosages of anti-hypertensive medications can be included.
Data sourced from ClinicalTrials.gov (NCT01163851). 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.