Clinical trial NCT01965600: A Study To Evaluate The Safety And Effects On The Body Of An Investigational Drug Using An Endotoxin-Induced Inflammatory Response Model
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Healthy
Keywords: Endotoxin challenge
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2013-10-18
Enrollment: 23
Sex: ALL
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

Brief 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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Peak Myeloperoxidase (MPO) Activity Following Inflammatory Stimulus
timeFrame: Days 1, 3-5
measure: MPO Activity (Area Under the Concentration-time Profile From 0.5 to 2 Hours [AUC0.5-2hrs]) Following Inflammatory Stimulus
timeFrame: Days 1, 3-5
measure: MPO Activity (Area Under the Concentration-time Profile From 0 to 2 Hours [AUC0-2hrs]) Following Inflammatory Stimulus
timeFrame: Days 1, 3-5
measure: Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Withdrawals Due to TEAEs
timeFrame: From Day 0 till approximately 7-10 days following the last dose of PF-06282999/Placebo in Period 2 (up to approximately 2 months)
measure: Number of Participants With Laboratory Test Abnormalities
timeFrame: Baseline up to 7-10 days following the last dose of PF-06282999/Placebo in Period 2
measure: Number of Participants With Change From Baseline and Absolute Values in Vital Signs Meeting Categorical Summarization Criteria
timeFrame: Screening and Days 1-2, 4-5, and approximately 7-10 days following the last dose of PF-06282999/Placebo in Period 2 for orthostatic (orth) measurements; Day 3 for supine measurements
measure: Number of Participants With Electrocardiogram (ECG) Values Meeting Categorical Summarization Criteria
timeFrame: Screening; Days 1-5 and approximately 7-10 days following the last dose of PF-06282999/Placebo in Period 2
measure: Number of Participants With Abnormal Urinary Biomarker Values
timeFrame: Days 1-3 prior to dosing with PF-06282999/Placebo; and Days 4-5
Secondary outcomes:
measure: Concentrations of TNF-alpha, IL-1 Beta, IL-6, IL-8, and hsCRP
timeFrame: Days 1, 3, and 4
measure: Peak (AUC0.5-2hours and AUC0-2hours) of MPO Activity/MPO Mass
timeFrame: Days 1, 3-5
measure: Maximum Plasma Concentration (Cmax) of PF-06282999
timeFrame: Day 3
measure: Area Under the Concentration-time Profile From Time 0 to End of Dosing Interval, Tau (AUCtau) of PF-06282999
timeFrame: Day 3
measure: Time to Cmax (Tmax) of PF-06282999
timeFrame: Day 3
Other outcomes:
Locations:
city: Durham
country: United States
facility: (Drug Shipment Address ONLY) Duke University Health Systems (DUHS) Investigational Drug Services
state: North Carolina
city: Durham
country: United States
facility: Duke Clinical Research Unit
state: North Carolina
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: