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CompletedNCT01435382Updated Jul 23, 2018Results posted

A Pharmacokinetic and Pharmacodynamic Study of PF-04950615 (RN316) in Subjects With Hypercholesterolemia

A Phase 1 interventional study of PF-04950615 (RN316) and PF-04950615 (RN316) in Hypercholesterolemia, Dyslipidemias and Hyperlipidemias, sponsored by Pfizer. Completed at 7 sites in United States. Open to participants aged 18 Years and older, including healthy volunteers. Per ClinicalTrials.gov, last updated 2018-07-23.

Sponsored by Pfizer · Phase 1, Interventional, and Basic science

Phase
Phase 1
Study type
Interventional
Enrollment
49
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study 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.

02

Conditions studied

  • Hypercholesterolemia
  • Dyslipidemias
  • Hyperlipidemias
  • Lipid Metabolism Disorders
  • Metabolic Diseases

Keywords

  • PF-04950615
  • RN316
03

In context

Hypercholesterolemia

1,238 studies on the registry are indexed under Hypercholesterolemia; 110 are open to participants now.

This study's enrollment of 49 is below the median of 100 across 992 interventional studies indexed under Hypercholesterolemia.

Browse Hypercholesterolemia studies →

Lead sponsor

Pfizer is the lead sponsor of 3,244 studies on the registry; 139 are open to participants now.

Of its 582 completed or terminated interventional studies of FDA-regulated products, 381 (65%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
Yes

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

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.
05

Study design

Phase
Phase 1
Primary purpose
Basic science
Allocation
Randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
49 participants (actual)

Study arms

  • Experimental
    Group A

    Biological: PF-04950615 (RN316)

  • Experimental
    Group B

    Biological: PF-04950615 (RN316)

  • Experimental
    Group C

    Biological: PF-04950615 (RN316)

  • Experimental
    Group D

    Biological: PF-04950615 (RN316)

Interventions

  • BiologicalPF-04950615 (RN316)

    Dose A - single-dose intravenous infusion

  • BiologicalPF-04950615 (RN316)

    Dose B - single-dose subcutaneous injection

  • BiologicalPF-04950615 (RN316)

    Dose C - single-dose subcutaneous injection

  • BiologicalPF-04950615 (RN316)

    Dose D - single-dose subcutaneous injection

06

What researchers measure

Primary outcomes

  1. 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

  2. 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

  3. 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

  4. 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

  5. Apparent Clearance (CL/F) of PF-04950615 Subcutaneous Groups

    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.

    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

  6. Clearance (CL) of PF-04950615 Intravenous Group

    Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes.

    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

  7. Apparent Volume of Distribution (Vz/F) of PF-04950615 Subcutaneous Groups

    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.

    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

  8. Volume of Distribution at Steady State (Vss) of PF-04950615 Intravenous Group

    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.

    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

  9. Terminal Elimination Half-life (t1/2) of PF-04950615

    t1/2 is the time measured for the plasma concentration of drug to decrease by one half.

    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

  10. Absolute Bioavailability of PF-04950615 Subcutaneous Groups

    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.

    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

Secondary outcomes

  1. 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

  2. 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

    Baseline was the average of observations collected on Days 7 and 1 prior to the study treatment administration.

    Time frame: Baseline, Day 2, 3, 4, 5, 6, 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, 85

  3. Duration of Fasting LDL-C Suppressed Below 70 mg/dL and 100 mg/dL

    Time frame: Day 1 up to Day 85

Other outcomes

  1. Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)

    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.

    Time frame: Day 1 up to Day 85

  2. Number of Adverse Events (AEs) by Severity

    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).

    Time frame: Day 1 up to Day 85

  3. Number of Participants With Treatment Related Adverse Events (AEs) and Serious Adverse Events (SAEs)

    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.

    Time frame: Day 1 up to Day 85

  4. Number of Participants With Injection Site Reactions

    The injection site reaction included erythema, induration, ecchymosis, injection site pain, injection site pruritus.

    Time frame: Day 1 up to Day 3

  5. Number of Injection Site Reactions Reported as Adverse Events

    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.

    Time frame: Day 1 up to Day 3

  6. Visual Analogue Scale (VAS)

    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.

    Time frame: Day 1: Immediately post-dose, 0.5, 1.0, 2.0, 8.0 hours post-dose; Day 2, 3

  7. Number of Participants With Clinically Significant Laboratory Abnormalities

    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.

    Time frame: Day 1 up to Day 85

  8. Number of Participants With Clinically Significant Changes in Vital Signs

    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.

    Time frame: Day 1 up to Day 85

  9. Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG)

    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.

    Time frame: Day 1 up to Day 85

  10. Percentage of Participants With Positive Anti-drug (Anti-PF 04950615) Antibodies

    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).

    Time frame: Day 1 up to Day 85

07

Results

Posted Jul 23, 2018

Participant flow

Participant flow — Overall Study
MilestonePF-04950615 IV 200 mgPF-04950615 SC 200 mg (2 Injections of 1 mL)PF-04950615 SC 200 mg (1 Injection of 2 mL)PF-04950615 SC 100 mg (1 Injection of 1 mL)
Started12131311
Completed11111210
Not completed1211
Withdrew: Lost to follow-up1010
Withdrew: Withdrawal by subject0201

Outcome measures

PrimaryMaximum 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
Reported as:
Mean · nanogram per milliliter (ng/mL)
Maximum Observed Plasma Concentration (Cmax) of PF-04950615
nanogram per milliliter (ng/mL)PF-04950615 IV 200 mgPF-04950615 SC 200 mg (2 Injections of 1 mL)PF-04950615 SC 200 mg (1 Injection of 2 mL)PF-04950615 SC 100 mg (1 Injection of 1 mL)
Maximum Observed Plasma Concentration (Cmax) of PF-0495061565810 ± 1404715900 ± 182898922 ± 4016.410470 ± 18219
PrimaryTime 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
Reported as:
Median · hour
Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-04950615
hourPF-04950615 IV 200 mgPF-04950615 SC 200 mg (2 Injections of 1 mL)PF-04950615 SC 200 mg (1 Injection of 2 mL)PF-04950615 SC 100 mg (1 Injection of 1 mL)
Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-049506151.00 (1.00 to 1.08)95.2 (8.00 to 167)96.0 (71.0 to 167)72.0 (8.00 to 504)
PrimaryArea 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
Reported as:
Mean · nanogram*hour per milliliter
Area Under the Plasma Concentration-Time Curve From Time Zero to Time of Last Quantifiable Concentration (AUClast) of PF-04950615
nanogram*hour per milliliterPF-04950615 IV 200 mgPF-04950615 SC 200 mg (2 Injections of 1 mL)PF-04950615 SC 200 mg (1 Injection of 2 mL)PF-04950615 SC 100 mg (1 Injection of 1 mL)
Area Under the Plasma Concentration-Time Curve From Time Zero to Time of Last Quantifiable Concentration (AUClast) of PF-0495061513360000 ± 36352003420000 ± 20241002862000 ± 16380001529000 ± 849890
PrimaryArea 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
Reported as:
Mean · nanogram*hour per milliliter
Area Under the Plasma Concentration-Time Curve From Time Zero To Infinity (AUCinf) of PF-04950615
nanogram*hour per milliliterPF-04950615 IV 200 mgPF-04950615 SC 200 mg (2 Injections of 1 mL)PF-04950615 SC 200 mg (1 Injection of 2 mL)PF-04950615 SC 100 mg (1 Injection of 1 mL)
Area Under the Plasma Concentration-Time Curve From Time Zero To Infinity (AUCinf) of PF-0495061513510000 ± 36444003911000 ± 20086003173000 ± 17280001271000 ± 411160
PrimaryApparent Clearance (CL/F) of PF-04950615 Subcutaneous Groups

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.

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
Reported as:
Mean · milliliter per hour
Apparent Clearance (CL/F) of PF-04950615 Subcutaneous Groups
milliliter per hourPF-04950615 SC 200 mg (2 Injections of 1 mL)PF-04950615 SC 200 mg (1 Injection of 2 mL)PF-04950615 SC 100 mg (1 Injection of 1 mL)
Apparent Clearance (CL/F) of PF-04950615 Subcutaneous Groups71.64 ± 53.29380.08 ± 42.65485.54 ± 26.453
PrimaryClearance (CL) of PF-04950615 Intravenous Group

Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes.

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
Reported as:
Mean · milliliter per hour
Clearance (CL) of PF-04950615 Intravenous Group
milliliter per hourPF-04950615 IV 200 mg
Clearance (CL) of PF-04950615 Intravenous Group15.82 ± 4.3037
PrimaryApparent Volume of Distribution (Vz/F) of PF-04950615 Subcutaneous Groups

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.

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
Reported as:
Mean · milliliter
Apparent Volume of Distribution (Vz/F) of PF-04950615 Subcutaneous Groups
milliliterPF-04950615 SC 200 mg (2 Injections of 1 mL)PF-04950615 SC 200 mg (1 Injection of 2 mL)PF-04950615 SC 100 mg (1 Injection of 1 mL)
Apparent Volume of Distribution (Vz/F) of PF-04950615 Subcutaneous Groups17770 ± 1355519400 ± 1937118400 ± 6381.5
PrimaryVolume of Distribution at Steady State (Vss) of PF-04950615 Intravenous Group

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.

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
Reported as:
Mean · milliliter
Volume of Distribution at Steady State (Vss) of PF-04950615 Intravenous Group
milliliterPF-04950615 IV 200 mg
Volume of Distribution at Steady State (Vss) of PF-04950615 Intravenous Group4232 ± 757.77
PrimaryTerminal Elimination Half-life (t1/2) of PF-04950615

t1/2 is the time measured for the plasma concentration of drug to decrease by one half.

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
Reported as:
Mean · hour
Terminal Elimination Half-life (t1/2) of PF-04950615
hourPF-04950615 IV 200 mgPF-04950615 SC 200 mg (2 Injections of 1 mL)PF-04950615 SC 200 mg (1 Injection of 2 mL)PF-04950615 SC 100 mg (1 Injection of 1 mL)
Terminal Elimination Half-life (t1/2) of PF-04950615202.4 ± 76.391187.6 ± 87.298153.2 ± 49.106152.6 ± 43.324
PrimaryAbsolute Bioavailability of PF-04950615 Subcutaneous Groups

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.

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
Reported as:
Number · percentage of bioavailability
Absolute Bioavailability of PF-04950615 Subcutaneous Groups
percentage of bioavailabilityPF-04950615 SC 200 mg (2 Injections of 1 mL)PF-04950615 SC 200 mg (1 Injection of 2 mL)PF-04950615 SC 100 mg (1 Injection of 1 mL)
Absolute Bioavailability of PF-04950615 Subcutaneous Groups20.60 (13.74 to 30.87)21.24 (14.40 to 31.33)19.54 (13.25 to 28.83)
SecondaryAbsolute 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
Reported as:
Mean · milligram per deciliter (mg/dL)
Absolute Value of Fasting Low-density Lipoprotein Cholesterol (LDL-C)
milligram per deciliter (mg/dL)PF-04950615 IV 200 mgPF-04950615 SC 200 mg (2 Injections of 1 mL)PF-04950615 SC 200 mg (1 Injection of 2 mL)PF-04950615 SC 100 mg (1 Injection of 1 mL)
Day 2154.00 ± 30.899145.15 ± 29.653148.31 ± 29.965143.36 ± 24.250
Day 3147.33 ± 23.274132.54 ± 27.933138.31 ± 26.961134.18 ± 26.294
Day 4131.09 ± 20.637119.08 ± 31.481125.77 ± 29.936126.55 ± 27.883
Day 5126.67 ± 26.476104.46 ± 33.301116.46 ± 38.937119.91 ± 31.995
Day 6128.92 ± 34.82891.38 ± 26.355101.31 ± 30.872111.55 ± 29.733
Day 896.70 ± 17.25791.92 ± 40.01693.85 ± 32.695104.20 ± 20.896
Day 1568.73 ± 18.90669.67 ± 25.11569.83 ± 29.64973.00 ± 26.069
Day 2260.27 ± 14.14382.45 ± 38.50872.85 ± 28.801103.18 ± 32.230
Day 2965.82 ± 11.303126.18 ± 45.683115.75 ± 24.984142.64 ± 23.243
Day 3674.73 ± 23.749125.10 ± 34.962133.75 ± 24.458140.80 ± 25.529
Day 4396.00 ± 33.308142.45 ± 33.255140.75 ± 26.362149.60 ± 27.261
Day 50119.64 ± 28.790149.45 ± 49.178152.17 ± 25.074151.70 ± 29.691
Day 57150.20 ± 26.931155.73 ± 35.755152.25 ± 21.192163.40 ± 38.839
Day 64155.27 ± 36.072154.09 ± 30.164148.33 ± 20.637152.00 ± 32.139
Day 71151.00 ± 27.928149.91 ± 32.473148.00 ± 16.432141.80 ± 26.561
Day 85159.82 ± 21.577151.00 ± 26.461153.50 ± 28.688137.30 ± 18.325
SecondaryPercent 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

Baseline was the average of observations collected on Days 7 and 1 prior to the study treatment administration.

Time frame:
Baseline, Day 2, 3, 4, 5, 6, 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, 85
Reported as:
Mean · percent change
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
percent changePF-04950615 IV 200 mgPF-04950615 SC 200 mg (2 Injections of 1 mL)PF-04950615 SC 200 mg (1 Injection of 2 mL)PF-04950615 SC 100 mg (1 Injection of 1 mL)
Day 2-5.93 ± 13.438-7.89 ± 11.329-7.05 ± 8.311-8.05 ± 10.310
Day 3-9.85 ± 7.085-16.31 ± 8.049-13.06 ± 9.137-14.27 ± 11.100
Day 4-17.87 ± 8.076-25.44 ± 9.346-21.20 ± 12.194-19.40 ± 11.037
Day 5-22.59 ± 11.972-34.84 ± 13.442-28.05 ± 16.909-23.83 ± 14.811
Day 6-21.59 ± 17.003-42.14 ± 12.827-36.62 ± 14.459-29.14 ± 13.507
Day 8-40.81 ± 13.225-43.18 ± 17.765-41.47 ± 16.099-34.00 ± 9.161
Day 15-58.13 ± 12.698-56.25 ± 13.925-56.45 ± 18.729-53.43 ± 14.985
Day 22-63.97 ± 7.455-48.49 ± 19.518-54.63 ± 15.528-34.63 ± 15.892
Day 29-60.61 ± 5.751-19.57 ± 23.437-27.49 ± 16.364-8.06 ± 14.174
Day 36-55.43 ± 13.394-20.45 ± 19.212-15.45 ± 20.597-9.42 ± 12.159
Day 43-42.94 ± 17.217-8.62 ± 14.204-10.12 ± 25.814-3.61 ± 13.949
Day 50-28.72 ± 14.755-5.91 ± 17.374-4.41 ± 15.372-2.38 ± 15.363
Day 57-10.00 ± 12.039-0.77 ± 10.237-4.63 ± 10.4934.51 ± 17.233
Day 64-7.59 ± 15.843-1.17 ± 9.787-6.94 ± 11.837-1.90 ± 19.561
Day 71-9.93 ± 10.904-4.10 ± 11.984-6.95 ± 10.454-8.87 ± 11.161
Day 85-3.67 ± 14.381-2.21 ± 15.821-3.47 ± 18.833-10.76 ± 13.458
SecondaryDuration of Fasting LDL-C Suppressed Below 70 mg/dL and 100 mg/dL
Time frame:
Day 1 up to Day 85
Reported as:
Mean · days
Duration of Fasting LDL-C Suppressed Below 70 mg/dL and 100 mg/dL
daysPF-04950615 IV 200 mgPF-04950615 SC 200 mg (2 Injections of 1 mL)PF-04950615 SC 200 mg (1 Injection of 2 mL)PF-04950615 SC 100 mg (1 Injection of 1 mL)
Below 70 mg/dL9.4 ± 8.258.7 ± 7.557.5 ± 7.624.5 ± 4.04
Below 100 mg/dL21.8 ± 12.6412.3 ± 10.4312.8 ± 9.838.8 ± 8.10
Other pre-specifiedNumber of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)

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.

Time frame:
Day 1 up to Day 85
Reported as:
Count of participants · Participants
Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
ParticipantsPF-04950615 IV 200 mgPF-04950615 SC 200 mg (2 Injections of 1 mL)PF-04950615 SC 200 mg (1 Injection of 2 mL)PF-04950615 SC 100 mg (1 Injection of 1 mL)
Adverse Events7786
Serious Adverse Events0000
Other pre-specifiedNumber of Adverse Events (AEs) by Severity

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).

Time frame:
Day 1 up to Day 85
Reported as:
Number · adverse events
Number of Adverse Events (AEs) by Severity
adverse eventsPF-04950615 IV 200 mgPF-04950615 SC 200 mg (2 Injections of 1 mL)PF-04950615 SC 200 mg (1 Injection of 2 mL)PF-04950615 SC 100 mg (1 Injection of 1 mL)
Mild1214135
Moderate0262
Severe0000
Other pre-specifiedNumber of Participants With Treatment Related Adverse Events (AEs) and Serious Adverse Events (SAEs)

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.

Time frame:
Day 1 up to Day 85
Reported as:
Count of participants · Participants
Number of Participants With Treatment Related Adverse Events (AEs) and Serious Adverse Events (SAEs)
ParticipantsPF-04950615 IV 200 mgPF-04950615 SC 200 mg (2 Injections of 1 mL)PF-04950615 SC 200 mg (1 Injection of 2 mL)PF-04950615 SC 100 mg (1 Injection of 1 mL)
Adverse Events3311
Serious Adverse Events0000
Other pre-specifiedNumber of Participants With Injection Site Reactions

The injection site reaction included erythema, induration, ecchymosis, injection site pain, injection site pruritus.

Time frame:
Day 1 up to Day 3
Reported as:
Count of participants · Participants
Number of Participants With Injection Site Reactions
ParticipantsPF-04950615 SC 200 mg (2 Injections of 1 mL)PF-04950615 SC 200 mg (1 Injection of 2 mL)PF-04950615 SC 100 mg (1 Injection of 1 mL)
Number of Participants With Injection Site Reactions254
Other pre-specifiedNumber of Injection Site Reactions Reported as Adverse Events

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.

Time frame:
Day 1 up to Day 3
Reported as:
Number · injection site reactions
Number of Injection Site Reactions Reported as Adverse Events
injection site reactionsPF-04950615 SC 200 mg (2 Injections of 1 mL)PF-04950615 SC 200 mg (1 Injection of 2 mL)PF-04950615 SC 100 mg (1 Injection of 1 mL)
Number of Injection Site Reactions Reported as Adverse Events000
Other pre-specifiedVisual Analogue Scale (VAS)

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.

Time frame:
Day 1: Immediately post-dose, 0.5, 1.0, 2.0, 8.0 hours post-dose; Day 2, 3
Reported as:
Mean · units on a scale
Visual Analogue Scale (VAS)
units on a scalePF-04950615 SC 200 mg (2 Injections of 1mL): Injection 1PF-04950615 SC 200 mg (2 Injections of 1mL): Injection 2PF-04950615 SC 200 mg (1 Injection of 2 mL)PF-04950615 SC 100 mg (1 Injection of 1 mL)
Day 1: Immediately post-dose3.678 ± 4.86182.308 ± 2.32323.824 ± 7.75233.273 ± 3.3194
Day 1: 0.5 hour1.462 ± 1.45001.769 ± 1.83283.208 ± 7.03881.455 ± 2.2962
Day 1: 1.0 hour1.231 ± 1.30091.462 ± 1.45001.228 ± 1.87711.364 ± 1.4334
Day 1: 2.0 hours1.651 ± 1.50211.462 ± 1.50641.305 ± 1.88741.455 ± 2.0181
Day 1: 8.0 hours1.231 ± 1.48061.308 ± 1.37751.077 ± 1.75411.182 ± 1.5374
Day 21.077 ± 1.32051.461 ± 1.56101.230 ± 2.16631.364 ± 1.5015
Day 3—0.990 ± NA——
Other pre-specifiedNumber of Participants With Clinically Significant Laboratory Abnormalities

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.

Time frame:
Day 1 up to Day 85
Reported as:
Count of participants · Participants
Number of Participants With Clinically Significant Laboratory Abnormalities
ParticipantsPF-04950615 IV 200 mgPF-04950615 SC 200 mg (2 Injections of 1 mL)PF-04950615 SC 200 mg (1 Injection of 2 mL)PF 04950615 SC 100 mg (1 Injection of 1 mL)
Number of Participants With Clinically Significant Laboratory Abnormalities0000
Other pre-specifiedNumber of Participants With Clinically Significant Changes in Vital Signs

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.

Time frame:
Day 1 up to Day 85
Reported as:
Count of participants · Participants
Number of Participants With Clinically Significant Changes in Vital Signs
ParticipantsPF-04950615 IV 200 mgPF-04950615 SC 200 mg (2 Injections of 1 mL)PF-04950615 SC 200 mg (1 Injection of 2 mL)PF-04950615 SC 100 mg (1 Injection of 1 mL)
Number of Participants With Clinically Significant Changes in Vital Signs1142
Other pre-specifiedNumber of Participants With Clinically Significant Changes in Electrocardiogram (ECG)

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.

Time frame:
Day 1 up to Day 85
Reported as:
Count of participants · Participants
Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG)
ParticipantsPF-04950615 IV 200 mgPF-04950615 SC 200 mg (2 Injections of 1 mL)PF-04950615 SC 200 mg (1 Injection of 2 mL)PF-04950615 SC 100 mg (1 Injection of 1 mL)
Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG)0000
Other pre-specifiedPercentage of Participants With Positive Anti-drug (Anti-PF 04950615) Antibodies

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).

Time frame:
Day 1 up to Day 85
Reported as:
Number · percentage of participants
Percentage of Participants With Positive Anti-drug (Anti-PF 04950615) Antibodies
percentage of participantsPF-04950615 IV 200 mgPF-04950615 SC 200 mg (2 Injections of 1 mL)PF-04950615 SC 200 mg (1 Injection of 2 mL)PF 04950615 SC 100 mg (1 Injection of 1 mL)
Percentage of Participants With Positive Anti-drug (Anti-PF 04950615) Antibodies8.3000

Adverse events

Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
PF-04950615 IV 200 mg—0/12 (0%)7/12 (58.3%)
PF-04950615 SC 200 mg (2 Injections of 1 mL)—0/13 (0%)7/13 (53.8%)
PF-04950615 SC 200 mg (1 Injection of 2 mL)—0/13 (0%)8/13 (61.5%)
PF-04950615 SC 100 mg (1 Injection of 1 mL)—0/11 (0%)6/11 (54.5%)
Most frequent other events
Showing 10 of 26
Most frequent other events
EventPF-04950615 IV 200 mgPF-04950615 SC 200 mg (2 Injections of 1 mL)PF-04950615 SC 200 mg (1 Injection of 2 mL)PF-04950615 SC 100 mg (1 Injection of 1 mL)
Upper respiratory tract infectionInfections and infestations3/122/133/134/11
HeadacheNervous system disorders2/123/133/131/11
Viral infectionInfections and infestations2/120/130/130/11
MyalgiaMusculoskeletal and connective tissue disorders2/121/130/131/11
GastroenteritisInfections and infestations0/120/132/130/11
Joint injuryInjury, poisoning and procedural complications0/120/130/131/11
Pain in extremityMusculoskeletal and connective tissue disorders1/120/131/130/11
AsthmaRespiratory, thoracic and mediastinal disorders1/120/130/130/11
Nasal congestionRespiratory, thoracic and mediastinal disorders1/121/131/130/11
Abdominal discomfortGastrointestinal disorders0/120/131/130/11

Baseline characteristics

All participants who received at least 1 dose of study medication.

Age, Continuous
Age, Continuous(years)PF-04950615 IV 200 mgPF-04950615 SC 200 mg (2 Injections of 1 mL)PF-04950615 SC 200 mg (1 Injection of 2 mL)PF-04950615 SC 100 mg (1 Injection of 1 mL)Total
Mean50.8 ± 9.955.6 ± 9.852.1 ± 6.953.2 ± 12.352.9 ± 9.7
Sex: Female, Male
Sex: Female, Male(Participants)PF-04950615 IV 200 mgPF-04950615 SC 200 mg (2 Injections of 1 mL)PF-04950615 SC 200 mg (1 Injection of 2 mL)PF-04950615 SC 100 mg (1 Injection of 1 mL)Total
Female447621
Male896528
08

Study locations

7 sites
  • Profil Institute for Clinical Research, Inc.
    Chula Vista, California 91911, United States
  • Elite Research Institute
    Miami, Florida 33169, United States
  • Vince and Associates Clinical Research
    Overland Park, Kansas 66212, United States
  • PAREXEL International - Baltimore Early Phase Clinical Unit
    Baltimore, Maryland 21225, United States
  • Jasper Clinic, Inc.
    Kalamazoo, Michigan 49007, United States
  • Prism Research
    Saint Paul, Minnesota 55114, United States
  • Medpace Clinical Pharmacology Unit
    Cincinnati, Ohio 45212, United States
09

References and documents

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. PubMed 28181260 ↗
10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Jul 23, 2018, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT01435382
Lead sponsor
Pfizer
Responsible party
Sponsor
First posted
Sep 16, 2011
Start date
Oct 2011
Primary completion
Feb 2012
Completion
Apr 2012
Results posted
Jul 23, 2018
Last update
Jul 23, 2018

Study contacts

Pfizer CT.gov Call Center
study director · Pfizer

Oversight

Data monitoring committee
No
View the source record on ClinicalTrials.gov ↗

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