NCT01163851

Brief Summary

The primary objective of this study is to evaluate the pharmacokinetics and pharmacodynamics of a single dose of PF-04950615 (RN316) in volunteers on stable doses of atorvastatin. PF-04950615 (RN316) is an investigational drug that is currently being studies as a cholesterol lowering therapy.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
25

participants targeted

Target at P25-P50 for phase_1

Timeline
Completed

Started Jul 2010

Geographic Reach
1 country

5 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

July 1, 2010

Completed
13 days until next milestone

First Submitted

Initial submission to the registry

July 14, 2010

Completed
2 days until next milestone

First Posted

Study publicly available on registry

July 16, 2010

Completed
7 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

February 1, 2011

Completed
2 months until next milestone

Study Completion

Last participant's last visit for all outcomes

April 1, 2011

Completed
4.1 years until next milestone

Results Posted

Study results publicly available

May 7, 2015

Completed
Last Updated

March 1, 2018

Status Verified

January 1, 2018

Enrollment Period

7 months

First QC Date

July 14, 2010

Results QC Date

April 20, 2015

Last Update Submit

January 31, 2018

Conditions

HypercholesterolemiaDyslipidemia

Keywords

HypercholesterolemiaDyslipidemiaLDLCholesterolHigh CholesterolPF-04950615RN316

Outcome Measures

Primary Outcomes (13)

  • Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of PF-04950615

    0 (pre-dose on Day 4), 1, 4, 8 and 12 hours (hrs) post intravenous PF-04950615 (RN316) dose, pre atorvastatin dose on Day 5, 6, 7, 15, 22, 29, 36, 43, 50, 57 and 64

  • Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-04950615

    0 (pre-dose on Day 4), 1, 4, 8 and 12 hours (hrs) post intravenous PF-04950615 (RN316) dose, pre atorvastatin dose on Day 5, 6, 7, 15, 22, 29, 36, 43, 50, 57 and 64

  • Maximum Observed Plasma Concentration (Cmax) of PF-04950615

    0 (pre-dose on Day 4), 1, 4, 8 and 12 hours (hrs) post intravenous PF-04950615 (RN316) dose, pre atorvastatin dose on Day 5, 6, 7, 15, 22, 29, 36, 43, 50, 57 and 64

  • Plasma Decay Half-Life (t1/2) of PF-04950615

    Plasma decay half-life is the time measured for the plasma concentration of PF-04950615 to decrease by one half.

    0 (pre-dose on Day 4), 1, 4, 8 and 12 hours (hrs) post intravenous PF-04950615 (RN316) dose, pre atorvastatin dose on Day 5, 6, 7, 15, 22, 29, 36, 43, 50, 57 and 64

  • Systemic Clearance (CL) of PF-04950615

    CL is a quantitative measure of the rate at which a drug substance is removed from the body.

    0 (pre-dose on Day 4), 1, 4, 8 and 12 hours (hrs) post intravenous PF-04950615 (RN316) dose, pre atorvastatin dose on Day 5, 6, 7, 15, 22, 29, 36, 43, 50, 57 and 64

  • Volume of Distribution at Steady State (Vss) of PF-04950615

    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 blood concentration of a drug.

    0 (pre-dose on Day 4), 1, 4, 8 and 12 hours (hrs) post intravenous PF-04950615 (RN316) dose, pre atorvastatin dose on Day 5, 6, 7, 15, 22, 29, 36, 43, 50, 57 and 64

  • Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUC0-inf) of PF-04950615

    0 (pre-dose on Day 4), 1, 4, 8 and 12 hours (hrs) post intravenous PF-04950615 (RN316) dose, pre atorvastatin dose on Day 5, 6, 7, 15, 22, 29, 36, 43, 50, 57 and 64

  • Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of Atorvastatin

    AUCtau was the AUC from time 0 to the end of the dosing interval, where the dosing interval was 12 hours.

    0 (pre-dose), 0.25, 0.5, 1, 2, 3, 4, 6, 8 and 12 hrs post-dose on Day 4

  • Time to Reach Maximum Observed Plasma Concentration (Tmax) of Atorvastatin

    0 (pre-dose), 0.25, 0.5, 1, 2, 3, 4, 6, 8 and 12 hrs post-dose on Day 4, pre atorvastatin dose on Day 5, 6 and 7

  • Maximum Observed Plasma Concentration (Cmax) of Atorvastatin

    0 (pre-dose), 0.25, 0.5, 1, 2, 3, 4, 6, 8 and 12 hrs post-dose on Day 4, pre atorvastatin dose on Day 5, 6 and 7

  • Plasma Decay Half-Life (t1/2) of Atorvastatin

    Plasma decay half-life is the time measured for the plasma concentration of atorvastatin to decrease by one half.

    0 (pre-dose), 0.25, 0.5, 1, 2, 3, 4, 6, 8 and 12 hrs post-dose on Day 4, pre atorvastatin dose on Day 5, 6 and 7

  • Apparent Oral Clearance (CL/F) of Atorvastatin

    Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed.

    0 (pre-dose), 0.25, 0.5, 1, 2, 3, 4, 6, 8 and 12 hrs post-dose on Day 4

  • Apparent Volume of Distribution (Vz/F) of Atorvastatin

    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. Apparent volume of distribution after oral dose (Vz/F) is influenced by the fraction absorbed.

    0 (pre-dose), 0.25, 0.5, 1, 2, 3, 4, 6, 8 and 12 hrs post-dose on Day 4

Secondary Outcomes (24)

  • Change From Baseline in Fasting Low Density Lipoprotein-Cholesterol (LDL-C) at Day 5, 6, 7, 15, 22, 29, 36, 43, 50, 57 and 64

    Baseline, Day 5, 6, 7, 15, 22, 29, 36, 43, 50, 57, 64

  • Change From Baseline in Fasting Total Cholesterol at Day 5, 6, 7, 15, 22, 29, 36, 43, 50, 57 and 64

    Baseline, Day 5, 6, 7, 15, 22, 29, 36, 43, 50, 57, 64

  • Change From Baseline in Fasting Non High-density Lipoprotein-Cholesterol (Non-HDL-C) at Day 5, 6, 7, 15, 22, 29, 36, 43, 50, 57 and 64

    Baseline, Day 5, 6, 7, 15, 22, 29, 36, 43, 50, 57, 64

  • Change From Baseline in Fasting Triglycerides at Day 5, 6, 7, 15, 22, 29, 36, 43, 50, 57 and 64

    Baseline, Day 5, 6, 7, 15, 22, 29, 36, 43, 50, 57, 64

  • Change From Baseline in Fasting Apolipoprotein B (ApoB) at Day 5, 6, 7, 15, 22, 29, 36, 43, 50, 57 and 64

    Baseline, Day 5, 6, 7, 15, 22, 29, 36, 43, 50, 57, 64

  • +19 more secondary outcomes

Study Arms (1)

PF-04950615 (RN316)

EXPERIMENTAL
Biological: 4 mg/kgBiological: 0.5 mg/kg

Interventions

4 mg/kgBIOLOGICAL

RN316 10 mg/ml vial sd. Infusion based on weight Infusion duration = 60 minutes.

Also known as: PF-04950615 (RN316)
PF-04950615 (RN316)
0.5 mg/kgBIOLOGICAL

RN316 10 mg/ml vial sd. Infusion based on weight Infusion duration = 60 minutes.

Also known as: PF-04950615 (RN316)
PF-04950615 (RN316)

Eligibility Criteria

Age18 Years - 80 Years
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • On stable doses of atorvastatin (40 mg daily) for 45 days prior to Day 1.
  • BMI 18.5 to 40 kg/m2 inclusive, and body weight equal or lower than 150 kg.

You may not qualify if:

  • History of a cardiovascular event (e.g., MI ) during the past year.
  • Poorly controlled Type 1 or Type 2 Diabetes mellitus (definition: uncontrolled diabetes is defined as HBIAc \>9%).
  • Poorly controlled hypertension (uncontrolled hypertension is defined as a systolic blood pressure greater than 140 mm Hg or a diastolic blood pressure greater than 90 mm Hg, even with treatment). Subjects who have hypertension and are controlled on stable dosages of anti-hypertensive medications can be included.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (5)

Premier Research Group, Limited

Peoria, Arizona, 85381, United States

Location

Dedicated Phase 1, Inc.

Phoenix, Arizona, 85013, United States

Location

Premier Research Group Limited

Phoenix, Arizona, 85027, United States

Location

Vince and Associates Clinical Research

Overland Park, Kansas, 66211, United States

Location

Vince and Associates Clinical Research

Overland Park, Kansas, 66212, United States

Location

Related Publications (2)

  • Wang EQ, Kaila N, Plowchalk D, Gibiansky L, Yunis C, Sweeney K. Population PK/PD modeling of low-density lipoprotein cholesterol response in hypercholesterolemic participants following administration of bococizumab, a potent anti-PCSK9 monoclonal antibody. CPT Pharmacometrics Syst Pharmacol. 2023 Dec;12(12):2013-2026. doi: 10.1002/psp4.13050. Epub 2023 Nov 22.

    PMID: 37994400DERIVED

  • 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.

    PMID: 28181260DERIVED

Related Links

MeSH Terms

Conditions

HypercholesterolemiaDyslipidemias

Interventions

bococizumab

Condition Hierarchy (Ancestors)

HyperlipidemiasLipid Metabolism DisordersMetabolic DiseasesNutritional and Metabolic Diseases

Limitations and Caveats

All determinations of primary or secondary outcomes were arbitrary as study did not specify primary or secondary outcome measures.

Results Point of Contact

Title
Pfizer ClinicalTrials.gov Call Center
Organization
Pfizer, Inc.
ClinicalTrials.gov_Inquiries@pfizer.com
1-800-718-1021

Study Officials

  • Pfizer CT.gov Call Center

    Pfizer

    STUDY DIRECTOR

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
OTHER
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

July 14, 2010

First Posted

July 16, 2010

Study Start

July 1, 2010

Primary Completion

February 1, 2011

Study Completion

April 1, 2011

Last Updated

March 1, 2018

Results First Posted

May 7, 2015

Record last verified: 2018-01

Locations

US(5)