A Study To Evaluate The Safety And Effects On The Body Of An Investigational Drug Using An Endotoxin-Induced Inflammatory Response Model

Healthy Clinical Trial

— POM  

Official title:

A Phase 1, Randomized, Double Blind, Placebo Controlled, Multiple Dose, 2 Way Crossover Study To Evaluate The Safety And Pharmacodynamic Effects Of Pf 06282999 Using An Endotoxin (Lipopolysaccharide) Induced Inflammatory Response Model In Healthy Adult Subjects

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01965600
• Other study ID #: B5211007
• Secondary ID: 2013-001528-20
• Status: Terminated
• Phase: Phase 1
• First received: October 15, 2013
• Last updated: July 6, 2015
• Start date: March 2014
• Est. completion date: February 2015

Study information

• Verified date: July 2015
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

An endotoxin challenge will be administered to healthy subjects to induce production of inflammatory markers. An investigational drug or placebo will be administered prior to the endotoxin challenge to assess the effect of the investigational drug on the markers of inflammation. Safety and tolerability will also be assessed.

Description:

The trial was terminated on 25 March 2015 due to safety concerns regarding the administration of endotoxin and because of the uncertain availability of future endotoxin lots.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 23
• Est. completion date: February 2015
• Est. primary completion date: February 2015
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 40 Years

Eligibility

Inclusion Criteria:

• Healthy men or women (non-childbearing potential) between the ages of 18-40 years.

• Body Mass Index (BMI) 18-30 kg/m2 and a total body weight >50 kg (110 lbs).

Exclusion Criteria:

• History or evidence of habitual use of tobacco- or nicotine-containing products within 3 months of screening.

• History of frequent headaches or migraines (>3 per month), or headaches from an absence of caffeine.

• Caffeine consumption in excess of 3 cups per day.

• Subjects who have experienced cold/flu symptoms (ie, runny nose, cough, and/or fever) within 2 weeks of the first administration of study drug/placebo of each period.

• History of recurrent or chronic infections of any type such as tuberculosis, sinusitis, urinary tract infection, respiratory tract or dental (abscess) infection, etc. Also excluded are subjects with recurrent oral or genital herpes, recurrent herpes zoster, or any infection otherwise judged by the investigator to have the potential for worsening if enrolled in this study.

• Treatment with LPS in the past 12 months and/or a history of an allergic type reaction or known hypersensitivity to endotoxin at any time.

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Healthy

Intervention

Drug:
• PF-06282999
Tablet, 125 mg, TID, 3 days, 1 of 2 periods
• Placebo
Tablet, 0 mg, TID, 3 days, 1 of 2 periods

Other:
• LPS
IV bolus, 4 ng/kg, 1 day, QD, 2 of 2 periods

Drug:
• PF-06282999
Tablet, 500 mg, BID, 3 days, 1 of 2 periods
• Placebo
Tablet, 0 mg, BID, 3 days, 1 of 2 periods

Other:
• LPS
IV bolus, 4 ng/kg, 1 day, QD, 2 of 2 periods

Locations

Country	Name	City	State
United States	Duke Clinical Research Unit	Durham	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	MPO activity	Day 3 timepoints are post-LPS administration	Day 1 Hr 0; Day 3 Hr 0, 2, 2.25, 2.5, 2.75, 3, 3.25, 3.5, 3.75, 4, 4.5, 5, 5.5, 6, 8, 10, 12, 24, 48	No
Secondary	TNF-alpha		Day 1 Hr 0; Day 3 Hr 2, 3, 4, 5, 6, 10, 24	No
Secondary	IL-1beta		Day 1 Hr 0; Day 3 Hr 2, 3, 4, 5, 6, 10, 24	No
Secondary	IL-6		Day 1 Hr 0; Day 3 Hr 2, 3, 4, 5, 6, 10, 24	No
Secondary	IL-8		Day 1 Hr 0; Day 3 Hr 2, 3, 4, 5, 6, 10, 24	No
Secondary	hs-CRP		Day 1 Hr 0; Day 3 Hr 8, 24	No
Secondary	MPO activity/MPO mass		Day 1 Hr 0; Day 3 Hr 0, 2, 2.25, 2.5, 2.75, 3, 3.25, 3.5, 3.75, 4, 4.5, 5, 5.5, 6, 8, 10, 12, 24, 48	No
Secondary	Maximum Observed Plasma Concentration (Cmax)		Day 3 Hr 0, 2, 3, 4, 5, 6, 8, 12	No
Secondary	Area Under the Curve from Time Zero to end of dosing interval (AUCtau)		Day 3 Hr 0, 2, 3, 4, 5, 6, 8, 12	No
Secondary	Time to Reach Maximum Observed Plasma Concentration (Tmax)		Day 3 Hr 0, 2, 3, 4, 5, 6, 8, 12	No

External Links

•   To obtain contact information for a study center near you, click here.