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

Phase 2

Completed

• Conditions: Hypercholesterolemia
• Interventions: Drug: PBO; Drug: 200mg PF-04950615 (RN316); Drug: PF-04950615; Drug: 300mg PF-04950615 (RN316)

• Registration Number: NCT01592240
• Lead Sponsor: Pfizer

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2012-05-03
• Study First Submitted QC: 2012-05-04
• Study First Posted: 2012-05-07
• Study Start: 2012-07
• Primary Completion: 2013-04
• Study Completion: 2013-05
• Disposition First Submitted: 2014-10-14
• Disposition First Submitted QC: 2014-10-14
• Disposition First Posted: 2014-10-23
• Status Verified: 2017-10
• Results First Submitted: 2017-10-27
• Results First Submitted QC: 2017-10-27
• Last Update Submitted: 2017-10-27
• Results First Posted: 2017-12-05
• Last Update Posted: 2017-12-05

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 354

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Q28d Dosing Arm	200mg PF-04950615 (RN316)	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.
Q28d Dosing Arm	300mg PF-04950615 (RN316)	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.
Q28d Dosing Arm	PBO	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.
Q14d Dosing Arm	PBO	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.
Q14d Dosing Arm	PF-04950615	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.

Primary Outcome Measures

Name	Time	Method
Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) at Week 12	Baseline, Week 12

Secondary Outcome Measures

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

Trial Locations

Locations (70)

Achieve Clinical Research, LLC; 🇺🇸 Birmingham, Alabama, United States

Medical Affiliated Research Center, Inc.; 🇺🇸 Huntsville, Alabama, United States

The Office of James G. McMurray, MD; 🇺🇸 Huntsville, Alabama, United States

Southwest Heart Group; 🇺🇸 Tucson, Arizona, United States

Aureus Research Inc.; 🇺🇸 Little Rock, Arkansas, United States

Universal Biopharma Research Institute Inc. - Alta Family Health Clinic; 🇺🇸 Dinuba, California, United States

Clinical Trials Research; 🇺🇸 Lincoln, California, United States

The Office of Lucita M. Cruz, MD, Inc.; 🇺🇸 Norwalk, California, United States

Radiant Research; 🇺🇸 Santa Rosa, California, United States

St. Joseph's Medical Associates; 🇺🇸 Stockton, California, United States

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