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Trial record 1 of 1 for:    NCT01435382
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A Pharmacokinetic and Pharmacodynamic Study of PF-04950615 (RN316) in Subjects With Hypercholesterolemia

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ClinicalTrials.gov Identifier: NCT01435382
Recruitment Status : Completed
First Posted : September 16, 2011
Results First Posted : July 23, 2018
Last Update Posted : July 23, 2018
Sponsor:
Information provided by (Responsible Party):
Pfizer

Tracking Information
First Submitted Date  ICMJE September 7, 2011
First Posted Date  ICMJE September 16, 2011
Results First Submitted Date  ICMJE October 4, 2017
Results First Posted Date  ICMJE July 23, 2018
Last Update Posted Date July 23, 2018
Actual Study Start Date  ICMJE October 2011
Actual Primary Completion Date February 2012   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 6, 2017)
  • Maximum Observed Plasma Concentration (Cmax) of PF-04950615 [ Time Frame: Pre-dose, 30 minutes, 1, 8, 24, 48, 72, 96, 120, 168, 336, 504, 672, 840, 1008, 1176, 1344, 1512, 1680, 2016 hours post-dose ]
  • Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-04950615 [ Time Frame: Pre-dose, 30 minutes, 1, 8, 24, 48, 72, 96, 120, 168, 336, 504, 672, 840, 1008, 1176, 1344, 1512, 1680, 2016 hours post-dose ]
  • Area Under the Plasma Concentration-Time Curve From Time Zero to Time of Last Quantifiable Concentration (AUClast) of PF-04950615 [ Time Frame: Pre-dose, 30 minutes, 1, 8, 24, 48, 72, 96, 120, 168, 336, 504, 672, 840, 1008, 1176, 1344, 1512, 1680, 2016 hours post-dose ]
  • Area Under the Plasma Concentration-Time Curve From Time Zero To Infinity (AUCinf) of PF-04950615 [ Time Frame: Pre-dose, 30 minutes, 1, 8, 24, 48, 72, 96, 120, 168, 336, 504, 672, 840, 1008, 1176, 1344, 1512, 1680, 2016 hours post-dose ]
  • Apparent Clearance (CL/F) of PF-04950615 Subcutaneous Groups [ Time Frame: Pre-dose, 30 minutes, 1, 8, 24, 48, 72, 96, 120, 168, 336, 504, 672, 840, 1008, 1176, 1344, 1512, 1680, 2016 hours post-dose ]
    Clearance (CL) of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Apparent clearance (CL/F) is influenced by the fraction of the dose absorbed from plasma after SC administration of drug.
  • Clearance (CL) of PF-04950615 Intravenous Group [ Time Frame: Pre-dose, 30 minutes, 1, 8, 24, 48, 72, 96, 120, 168, 336, 504, 672, 840, 1008, 1176, 1344, 1512, 1680, 2016 hours post-dose ]
    Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes.
  • Apparent Volume of Distribution (Vz/F) of PF-04950615 Subcutaneous Groups [ Time Frame: Pre-dose, 30 minutes, 1, 8, 24, 48, 72, 96, 120, 168, 336, 504, 672, 840, 1008, 1176, 1344, 1512, 1680, 2016 hours post-dose ]
    Volume of distribution (Vz) is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Vz/F is influenced by the fraction of the dose absorbed from plasma after SC administration of drug.
  • Volume of Distribution at Steady State (Vss) of PF-04950615 Intravenous Group [ Time Frame: Pre-dose, 30 minutes, 1, 8, 24, 48, 72, 96, 120, 168, 336, 504, 672, 840, 1008, 1176, 1344, 1512, 1680, 2016 hours post-dose ]
    Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Vss is determined when overall intake of drug is in dynamic equilibrium with its elimination.
  • Terminal Elimination Half-life (t1/2) of PF-04950615 [ Time Frame: Pre-dose, 30 minutes, 1, 8, 24, 48, 72, 96, 120, 168, 336, 504, 672, 840, 1008, 1176, 1344, 1512, 1680, 2016 hours post-dose ]
    t1/2 is the time measured for the plasma concentration of drug to decrease by one half.
  • Absolute Bioavailability of PF-04950615 Subcutaneous Groups [ Time Frame: Pre-dose, 30 minutes, 1, 8, 24, 48, 72, 96, 120, 168, 336, 504, 672, 840, 1008, 1176, 1344, 1512, 1680, 2016 hours post-dose ]
    Bioavailability is defined as the rate and extent to which the active moiety administered drug reaches the systemic circulation. Absolute bioavailability of the subcutaneous doses was estimated by comparing log-transformed dose-normalized AUClast for subcutaneous to intravenous dose.
Original Primary Outcome Measures  ICMJE
 (submitted: September 15, 2011)
  • Maximum Observed Plasma Concentration (Cmax) of PF-04950615 [ Time Frame: Days 1, 2, 3, 4, 5, 6, 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, 85 ]
  • Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-04950615 [ Time Frame: Days 1, 2, 3, 4, 5, 6, 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, 85 ]
  • Area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration (AUClast) of PF-04950615 [ Time Frame: Days 1, 2, 3, 4, 5, 6, 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, 85 ]
  • Area under the plasma concentration-time curve extrapolated to infinity (AUCinf) of PF-04950615 [ Time Frame: Days 1, 2, 3, 4, 5, 6, 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, 85 ]
  • Clearance (CL/F or CL) of PF-04950615 [ Time Frame: Days 1, 2, 3, 4, 5, 6, 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, 85 ]
  • Volume of distribution (Vz/F or Vss) of PF-04950615 [ Time Frame: Days 1, 2, 3, 4, 5, 6, 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, 85 ]
  • Terminal Elimination Half-life (t1/2) of PF-04950615 [ Time Frame: Days 1, 2, 3, 4, 5, 6, 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, 85 ]
  • Absolute bioavailability (%F)of PF-04950615 [ Time Frame: Days 1, 2, 3, 4, 5, 6, 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, 85 ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: October 6, 2017)
  • Absolute Value of Fasting Low-density Lipoprotein Cholesterol (LDL-C) [ Time Frame: Day 2, 3, 4, 5, 6, 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, 85 ]
  • Percent Change From Baseline in Fasting Low-density Lipoprotein Cholesterol (LDL-C) at Day 2, 3, 4, 5, 6, 8, 15, 22, 29, 36, 43, 50, 57, 64, 71 and 85 [ Time Frame: Baseline, Day 2, 3, 4, 5, 6, 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, 85 ]
    Baseline was the average of observations collected on Days 7 and 1 prior to the study treatment administration.
  • Duration of Fasting LDL-C Suppressed Below 70 mg/dL and 100 mg/dL [ Time Frame: Day 1 up to Day 85 ]
Original Secondary Outcome Measures  ICMJE
 (submitted: September 15, 2011)
  • Absolute values of fasting LDL-C after PF-04950615 administration [ Time Frame: Up to 85 days ]
  • Percent change from baseline of fasting LDL-C after PF-04950615 administration [ Time Frame: Up to 85 days ]
  • Duration of LDL-C lowering effects of PF-04950615 [ Time Frame: Up to 85 days ]
Current Other Pre-specified Outcome Measures
 (submitted: October 6, 2017)
  • Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: Day 1 up to Day 85 ]
    An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. A treatment emergent AE was defined as an event that emerged during the treatment period that was absent before treatment, or worsened during the treatment period relative to the pretreatment state.
  • Number of Adverse Events (AEs) by Severity [ Time Frame: Day 1 up to Day 85 ]
    An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An AE was assessed according to severity; mild (not causing any significant problem, dose adjustment not required), moderate (caused problem that does not interfere significantly with usual activities or the clinical status, dose adjustment needed due to adverse event) and severe (caused problem that interferes significantly with usual activities or the clinical status, study drug stopped due to adverse event).
  • Number of Participants With Treatment Related Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: Day 1 up to Day 85 ]
    An AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.
  • Number of Participants With Injection Site Reactions [ Time Frame: Day 1 up to Day 3 ]
    The injection site reaction included erythema, induration, ecchymosis, injection site pain, injection site pruritus.
  • Number of Injection Site Reactions Reported as Adverse Events [ Time Frame: Day 1 up to Day 3 ]
    The injection site reactions included erythema, induration, ecchymosis, injection site pain and injection site pruritus. An adverse event was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship.
  • Visual Analogue Scale (VAS) [ Time Frame: Day 1: Immediately post-dose, 0.5, 1.0, 2.0, 8.0 hours post-dose; Day 2, 3 ]
    Participants indicated the amount of pain experienced due to study drug injection, on a VAS of 0 (no pain) to 100 (very severe pain), where higher scores indicate higher intensity of pain.
  • Number of Participants With Clinically Significant Laboratory Abnormalities [ Time Frame: Day 1 up to Day 85 ]
    Laboratory parameters evaluated for abnormalities were: hematology (hemoglobin [Hgb], hematocrit, red blood cell [RBC] count, platelets, white blood cell count [WBC], lymphocytes, total neutrophils, basophils, eosinophils, monocytes); coagulation (partial thromboplastin time, prothrombin time [PT], PT international ratio); clinical chemistry (glucose, creatine kinase, amylase, lipase); liver function (total, direct and indirect bilirubin, aspartate aminotransferase [AT], alanine AT, gamma-glutamyl transferase, alkaline phosphatase, total protein, albumin, lactate dehydrogenase); renal function (blood urea nitrogen, creatinine, uric acid); urinalysis (urine- specific gravity, pH, glucose, ketones, blood/Hgb, nitrite, leukocyte, esterase, RBC, WBC, epithelial cells, hyaline cast and bacteria); lipid (cholesterol); electrolytes (sodium, potassium, chloride, calcium, magnesium, phosphate, bicarbonate). Clinical significance of laboratory abnormalities were judged by investigator.
  • Number of Participants With Clinically Significant Changes in Vital Signs [ Time Frame: Day 1 up to Day 85 ]
    Vital signs abnormalities included: maximum increase or decrease from baseline in supine systolic blood pressure (BP) greater than or equal to (>=) 30 millimeter of mercury (mmHg); maximum increase or decrease from baseline in supine diastolic BP of >=20 mmHg; supine pulse rate less than (<) 40 beats per minute (bpm) and greater than (>) 120 bpm; standing pulse rate less than (<) 40 beats per minute (bpm) and greater than (>) 140 bpm. Clinical significance of vital signs were judged by investigator.
  • Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG) [ Time Frame: Day 1 up to Day 85 ]
    ECG abnormalities included 1) PR interval: maximum >=300 maximum millisecond (msec), increase of >=25 percent (%) for baseline value of >200 msec and maximum increase of >=50% for baseline value of less than or equal to (<=) 200 msec; 2) QRS interval: maximum >=200 msec, maximum increase of >=25 % for baseline value of >100 msec and maximum increase of >=50% for baseline value of <=100 msec; 3) QT interval corrected using the Fridericia's formula (QTCF): 450 msec to <= 480 msec, 480 msec to <=500 msec, > 500 msec, maximum increase from baseline of >30 to <=60 msec and maximum increase from baseline of >60 msec. Clinical significance of ECG were judged by investigator.
  • Percentage of Participants With Positive Anti-drug (Anti-PF 04950615) Antibodies [ Time Frame: Day 1 up to Day 85 ]
    Human serum samples of participants who received PF-04950615 were analyzed for the presence of anti-PF-04950615 antibodies by using the semi quantitative enzyme-linked immunosorbent assay (ELISA).
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Pharmacokinetic and Pharmacodynamic Study of PF-04950615 (RN316) in Subjects With Hypercholesterolemia
Official Title  ICMJE A Phase 1, Open-label, Randomized, Single Dose, Parallel Group Study To Assess The Pharmacokinetics And Pharmacodynamics Of Pf-04950615 Following Subcutaneous And Intravenous Doses In Adult Subjects With Hypercholesterolemia
Brief Summary This Phase 1 study has been designed to evaluate the absolute bioavailability of PF-04950615 (RN316) in subjects with hypercholesterolemia who are not currently on lipid-lowering therapy.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Condition  ICMJE
  • Hypercholesterolemia
  • Dyslipidemias
  • Hyperlipidemias
  • Lipid Metabolism Disorders
  • Metabolic Diseases
Intervention  ICMJE
  • Biological: PF-04950615 (RN316)
    Dose A - single-dose intravenous infusion
  • Biological: PF-04950615 (RN316)
    Dose B - single-dose subcutaneous injection
  • Biological: PF-04950615 (RN316)
    Dose C - single-dose subcutaneous injection
  • Biological: PF-04950615 (RN316)
    Dose D - single-dose subcutaneous injection
Study Arms  ICMJE
  • Experimental: Group A
    Intervention: Biological: PF-04950615 (RN316)
  • Experimental: Group B
    Intervention: Biological: PF-04950615 (RN316)
  • Experimental: Group C
    Intervention: Biological: PF-04950615 (RN316)
  • Experimental: Group D
    Intervention: Biological: PF-04950615 (RN316)
Publications * Udata C, Garzone PD, Gumbiner B, Joh T, Liang H, Liao KH, Williams JH, Meng X. A Mechanism-Based Pharmacokinetic/Pharmacodynamic Model for Bococizumab, a Humanized Monoclonal Antibody Against Proprotein Convertase Subtilisin/Kexin Type 9, and Its Application in Early Clinical Development. J Clin Pharmacol. 2017 Jul;57(7):855-864. doi: 10.1002/jcph.867. Epub 2017 Feb 9.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: March 29, 2012)
49
Original Estimated Enrollment  ICMJE
 (submitted: September 15, 2011)
48
Actual Study Completion Date  ICMJE April 2012
Actual Primary Completion Date February 2012   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Fasting LDL-C greater than or equal to 130 mg/dL at two qualifying screening visits.
  • Total body weight greater than or equal to 50 kg (110 lbs) and less than or equal to 150 kg (330 lbs)

Exclusion Criteria:

  • Lipid-lowering prescription medications, homeopaths, herbal medicines, or nutritional supplements.
  • Poorly controlled type 1 or type 2 diabetes.
  • History of a cardiovascular or cerebrovascular event or related procedure during the past year.
  • Poorly controlled hypertension.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01435382
Other Study ID Numbers  ICMJE B1481006
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Pfizer
Study Sponsor  ICMJE Pfizer
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Pfizer CT.gov Call Center Pfizer
PRS Account Pfizer
Verification Date October 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP