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

• Low Density Lipoprotein-Cholesterol (LDL-C) will be assessed as change and % change from baseline at the end of week 12 following randomization [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
• Safety endpoints will include incidence of anti-drug antibody (ADA), injection site [ Time Frame: Month 6 ] [ Designated as safety issue: Yes ]
• Plasma steady-state PF-04950615 pharmacokinetic parameters what PK measurements are being done? [ Time Frame: Month 6 ] [ Designated as safety issue: No ]
• Proportion of subjects having LDL-C less than particular limits (<100mg/dL, <70 mg/dL, <40mg/L, <25mg/dL) [ Time Frame: Month 6 ] [ Designated as safety issue: No ]
• Total cholesterol will be assessed as change and % change from baseline at the end of week 12 following randomization [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
• Apolipoprotein B (ApoB) will be assessed as change and % change from baseline at the end of week 12 following randomization [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
• Apolipoprotein A1 (ApoA1), Apolipoprotein AII (ApoAII) will be assessed as change and % change from baseline at the end of week 12 following randomization [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
• Lipoprotein (a) (Lp(a)) will be assessed as change and % change from baseline at the end of week 12 following randomization [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
• High Density Lipoprotein (HDL)-cholesterol will be assessed as change and % change from baseline at the end of week 12 following randomization [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
• Very Low Density Lipoprotein (VLDL)-cholesterol will be assessed as change and % change from baseline at the end of week 12 following randomization [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
• Triglycerides will be assessed as change and % change from baseline at the end of week 12 following randomization [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
• non-HDL-cholesterol will be assessed as change and % change from baseline at the end of week 12 following randomization [ Time Frame: Week 12 ] [ Designated as safety issue: No ]

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.

• Drug: PBO
  Placebo Q28d
• Drug: 200mg PF-04950615 (RN316)
  PF-04950615 200 mg, Q28d
  Other Name: PF-04950615 (RN316)
• Drug: 300mg PF-04950615 (RN316)
  PF-04950615 300 mg, Q28d
  Other Name: PF-04950615 (RN316)
• Drug: PBO
  Placebo, Q14d
• Drug: PF-04950615
  PF-04950615 50mg, Q14d
  Other Name: PF-04950615 (RN316)
• Drug: PF-04950615
  PF-04950615 100 mg, Q14d
  Other Name: PF-04950615 (RN316)
• Drug: PF-04950615
  PF-04950615 150mg, Q14d
  Other Name: PF-04950615 (RN316)

• Experimental: Q28d Dosing Arm
  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.
  Interventions:

  • Drug: PBO
  • Drug: 200mg PF-04950615 (RN316)
  • Drug: 300mg PF-04950615 (RN316)
• Experimental: Q14d Dosing Arm
  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.
  Interventions:

  • Drug: PBO
  • Drug: PF-04950615
  • Drug: PF-04950615
  • Drug: PF-04950615

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.