Monthly And Twice Monthly Subcutaneous Dosing Of PF-04950615 (RN316) In Hypercholesterolemic Subjects On A Statin

Study Overview
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Brief Summary
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To evaluate the Low Density Lipoprotein-Cholesterol (LDL-C) lowering effect of PF-04950615 administered subcutaneously at monthly intervals, or twice monthly intervals in subjects with high cholesterol whose LDL-cholesterol is >/=80 mg/dL on background treatment with a statin.

Official Title
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A Phase 2b Double-blind, Randomized, Placebo-controlled, Parallel Group, Dose-ranging Study To Assess The Efficacy, Safety And Tolerability Of Pf-04950615 Following Monthly And Twice Monthly Subcutaneous Dosing For Six Months In Hypercholesterolemic Subjects On A Statin

Conditions
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Hypercholesterolemia

Intervention / Treatment
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* Drug: PBO
* Drug: 200mg PF-04950615 (RN316)
* Drug: 300mg PF-04950615 (RN316)
* Drug: PBO
* Drug: PF-04950615
* Drug: PF-04950615
* Drug: PF-04950615


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects should be receiving a stable dose (at least 6 weeks) of any statin and continue on same dose of statin for the duration of this trial. Lipids should meet the following criteria on a background treatment with a statin at 2 screening visits that occur at screening and at least 7 days prior to randomization on Day 1: Fasting LDL-C greater than or equal to 80 mg/dL (2.31 mmol/L); Fasting TG less than or equal to 400 mg/dL (4.52 mmol/L). Subject's fasting LDL-cholesterol must greater than or equal to 80 mg/dL (2.31 mmol/L at the initial screening visit, and the value at the second visit within 7 days of randomization must be not lower than 20% of this initial value to meet eligibility criterion for this trial. Exclusion Criteria: Participation in other studies within 3 months before the current study begins and/or during study participation. Severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the subject inappropriate for entry into this study. Pregnant females; breastfeeding females; males and females of childbearing potential not using highly effective contraception or not agreeing to continue highly effective contraception for at least 63 days after last dose of investigational product. History of a cardiovascular or cerebrovascular event or procedure (eg, MI, stroke, TIA, angioplasty) during the past 6 months. Congestive heart failure (CHF), NYHA functional classes III or IV. Poorly controlled type 1 or type 2 diabetes mellitus (defined as HbA1c >9%). Poorly controlled hypertension.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Q28d Dosing Arm<br>A total of 7 dose groups in two dosing schedules, 50 subjects per dose group are planned. Q28d dose group will receive subcutaneous administration of PF-04950615 or Placebo once a month. | Drug: PBO<br>* Placebo Q28d<br>Drug: 200mg PF-04950615 (RN316)<br>* PF-04950615 200 mg, Q28d<br>* Other names: PF-04950615 (RN316);Drug: 300mg PF-04950615 (RN316)<br>* PF-04950615 300 mg, Q28d<br>* Other names: PF-04950615 (RN316);|
| Experimental: Q14d Dosing Arm<br>A total of 7 dose groups in two dosing schedules, 50 subjects per dose group are planned. Q14d dose group will receive subcutaneous administration of PF-04950615 or Placebo every 2 weeks. | Drug: PBO<br>* Placebo, Q14d<br>Drug: PF-04950615<br>* PF-04950615 50mg, Q14d<br>* Other names: PF-04950615 (RN316);Drug: PF-04950615<br>* PF-04950615 100 mg, Q14d<br>* Other names: PF-04950615 (RN316);Drug: PF-04950615<br>* PF-04950615 150mg, Q14d<br>* Other names: PF-04950615 (RN316);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) at Week 12 |  | Baseline, Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) at Week 24 |  | Baseline, Week 24 | 
| Percent Change From Baseline in Low Density Lipoprotein Cholesterol (LDL-C) at Week 12 and 24 |  | Baseline, Week 12, 24 | 
| Change From Baseline in High Density Lipoprotein Cholesterol (HDL-C) at Week 12 and 24 |  | Baseline, Week 12, 24 | 
| Percent Change From Baseline in High Density Lipoprotein Cholesterol (HDL-C) at Week 12 and 24 |  | Baseline, Week 12, 24 | 
| Change From Baseline in Apolipoprotein B (ApoB) at Week 12 and 24 |  | Baseline, Week 12, 24 | 
| Percent Change From Baseline in Apolipoprotein B (ApoB) at Week 12 and 24 |  | Baseline, Week 12, 24 | 
| Change From Baseline in Apolipoprotein A1 (ApoA1) at Week 12 and 24 |  | Baseline, Week 12, 24 | 
| Percent Change From Baseline in Apolipoprotein A1 (ApoA1) at Week 12 and 24 |  | Baseline, Week 12, 24 | 
| Change From Baseline in Apolipoprotein AII (ApoAII) at Week 12 and 24 |  | Baseline, Week 12, 24 | 
| Percent Change From Baseline in Apolipoprotein AII (ApoAII) at Week 12 and 24 |  | Baseline, Week 12, 24 | 
| Change From Baseline in Total Cholesterol at Week 12 and 24 |  | Baseline, Week 12, 24 | 
| Percent Change From Baseline in Total Cholesterol at Week 12 and 24 |  | Baseline, Week 12, 24 | 
| Change From Baseline in Lipoprotein (a) (Lp [a]) at Week 12 and 24 |  | Baseline, Week 12, 24 | 
| Percent Change From Baseline in Lipoprotein (a) (Lp [a]) at Week 12 and 24 |  | Baseline, Week 12, 24 | 
| Change From Baseline in Very Low Density Lipoprotein (VLDL) Cholesterol at Week 12 and 24 |  | Baseline, Week 12, 24 | 
| Percent Change From Baseline in Very Low Density Lipoprotein (VLDL) Cholesterol at Week 12 and 24 |  | Baseline, Week 12, 24 | 
| Change From Baseline in Triglycerides at Week 12 and 24 |  | Baseline, Week 12, 24 | 
| Percent Change From Baseline in Triglycerides at Week 12 and 24 |  | Baseline, Week 12, 24 | 
| Change From Baseline in Non-High Density Lipoprotein-Cholesterol (Non-HDL-C) at Week 12 and 24 |  | Baseline, Week 12, 24 | 
| Percent Change From Baseline in Non-High Density Lipoprotein-Cholesterol (Non-HDL-C) at Week 12 and 24 |  | Baseline, Week 12, 24 | 
| Percentage of Participants With Positive Anti-drug (Anti-PF-04950615) Antibodies (ADA) | Participants with titer value greater than or equal to 4.32 nanogram per milliliter were considered positive. | Baseline up to Day 211 for every 28 days groups and Baseline up to Day 225 for every 14 days groups | 
| Percentage of Participants With Injection Site Adverse Events | Injection site adverse events included injection site bruising, discomfort, erythema, hemorrhage, induration, inflammation, pain, paresthesia, pruritus, swelling, urticaria, reaction and rash. | Baseline up to Day 211 for 28 days groups and Baseline up to Day 225 for 14 days groups | 
| Plasma Concentration of PF-04950615 at Week 12 and 24 |  | Week 12, 24 | 
| Percentage of Participants With Low Density Lipoprotein-cholesterol Less Than (<) 100, <70, <40 and <25 Milligram Per Deciliter (mg/dL) |  | Week 12, 24 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PF-04950615, RN316