Clinical trial NCT02309827: Safety and Pharmacokinetic Study of PF-06651600 in Healthy Volunteers
Official title: A Phase 1, Randomized, Double Blind, Third-party Open, Placebo-controlled, Single And Multiple Dose Escalation, Parallel Group Study To Evaluate The Safety, Tolerability, Pharmacokinetics, And Pharmacodynamics Of Pf-06651600 In Healthy Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Keywords: Inflammatory bowel disease
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2014-12-05
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Primary purpose: TREATMENT

Brief summary: This study is a first in human study of PF-06651600. PF-06651600 is being developed for treatment of inflammatory bowel disease. This study will test single and multiple doses of PF-06651600. The goal of the study is to assess the safety, tolerability, pharmacokinetics and pharmacodynamics of PF-06651600 in healthy volunteers.


Eligibility criteria: Inclusion Criteria:

* Healthy male/female subjects between 18 and 55 years old, inclusive. Females must be of non-child bearing potential.
* BMI of 17.5 to 30.5 kg/m2; and a total body weight \>50 kg (110 lbs).
* Evidence of personally signed and dated informed consent document.
* Willing and able to comply with scheduled visits, treatment plan, lab tests and other study procedures.
* Subjects must avoid high intensity UV light exposure (eg, active sunbathing, tanning beds/booths or sunlamps) from the first dose of study drug and for the duration of the study.

Exclusion Criteria:

* Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, GI, cardiovascular, hepatic, psychiatric, neurologic, or allergic disease.
* Use of tobacco/nicotine containing products in excess of 5 cigarettes/day.
* History of regular alcohol consumption exceeding 14 drinks/week for females or 21 drinks/week for males.
* Screening blood pressure \>140/90 mm Hg.
* Screening laboratory abnormalities as defined by the protocol.
* Unwilling or unable to comply with the Lifestyle Guidelines as defined by the protocol.

Primary outcomes:
measure: 24 hour creatinine clearance (Single Dose)
timeFrame: Single dose period, Day 0 (baseline) and 24 hours post dose Day 1.
measure: 24 hour creatinine clearance (Multiple Dose)
timeFrame: Multiple dose period, Days 0 (baseline), 7 and 14.
measure: Change from baseline in urine volume (Single Dose)
timeFrame: Single dose period, Day 0 (baseline) and 24 hours post dose Day 1.
measure: Change from baseline in urine electrolytes (Single Dose)
timeFrame: Single dose period, Day 0 (baseline) and 24 hours post dose Day 1.
measure: Change from baseline in urine osmolality (Single Dose)
timeFrame: Single dose period, Day 0 (baseline) and 24 hours post dose Day 1.
measure: Change from baseline of urine volume (Multiple Dose)
timeFrame: Multiple dose period, Days 0 (baseline), 7 and 14.
measure: Change from baseline of urine electrolytes (Multiple Dose)
timeFrame: Multiple dose period, Days 0 (baseline), 7 and 14.
measure: Change from baseline in urine osmolality (Multiple Dose)
timeFrame: Multiple dose period, Days 0 (baseline), 7 and 14.
Secondary outcomes:
measure: Maximum Observed Plasma Concentration (Cmax) for PF-06651600 (Single Dose)
timeFrame: 0, 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, 48 hours post dose
measure: Maximum Observed Plasma Concentration (Cmax) for PF-06651600 (Multiple Dose)
timeFrame: Days 1, 4, 6, 8, 10, 12 and 14 (0, 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48 hours post dose)
measure: Time to Reach Maximum Observed Plasma Concentration (Cmax) for PF-06651600 (Single Dose)
timeFrame: 0, 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, 48 hours post dose
measure: Time to Reach Maximum Observed Plasma Concentration (Cmax) for PF-06651600 (Multiple Dose)
timeFrame: Days 1, 4, 6, 8, 10, 12 and 14 (0, 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48 hours post dose)
measure: Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) for PF-06651600 (Single Dose)
timeFrame: 0, 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, 48 hours post dose
measure: Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for PF-06651600 (Single Dose)
timeFrame: 0, 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, 48 hours post dose
measure: Dose Normalized Maximum Observed Plasma Concentration (Cmaxdn) for PF-06651600 (Single Dose)
timeFrame: 0, 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, 48 hours post dose
measure: Dose Normalized Maximum Observed Plasma Concentration (Cmaxdn) for PF-06651600 (Multiple Dose)
timeFrame: Days 1, 4, 6, 8, 10, 12 and 14 (0, 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48 hours post dose)
measure: Dose Normalized Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinfdn) for PF-06651600 (Single Dose)
timeFrame: 0, 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, 48 hours post dose
measure: Dose Normalized Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClastdn) for PF-06651600 (Single Dose)
timeFrame: 0, 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, 48 hours post dose
measure: Plasma Decay Half-Life (t1/2) for PF-06651600 (Single Dose)
timeFrame: 0, 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, 48 hours post dose
measure: Plasma Decay Half-Life (t1/2) for PF-06651600 (Multiple Dose)
timeFrame: Days 1, 4, 6, 8, 10, 12 and 14 (0, 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48 hours post dose)
measure: Mean Resonance Time (MRT) for PF-06651600 (Single Dose)
timeFrame: 0, 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, 48 hours post dose
measure: Mean Resonance Time (MRT) for PF-06651600 (Multiple Dose)
timeFrame: Days 1, 4, 6, 8, 10, 12 and 14 (0, 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48 hours post dose)
measure: Apparent Volume of Distribution (Vz/F) for PF-06651600 (Single Dose)
timeFrame: 0, 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, 48 hours post dose
measure: Apparent Volume of Distribution (Vz/F) for PF-06651600 (Multiple Dose)
timeFrame: Days 1, 4, 6, 8, 10, 12 and 14 (0, 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48 hours post dose)
measure: Apparent Total Body Clearance (CL/F) for PF-06651600 (Single Dose)
timeFrame: 0, 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, 48 hours post dose
measure: Apparent Total Body Clearance (CL/F) for PF-06651600 (Multiple Dose)
timeFrame: Days 1, 4, 6, 8, 10, 12 and 14 (0, 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48 hours post dose)
measure: Minimum Observed Plasma Concentration (Cmin) for PF-06651600 (Multiple Dose)
timeFrame: Days 1, 4, 6, 8, 10, 12 and 14 (0, 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48 hours post dose)
measure: Average Concentration for Dosing Interval (12 or 24 hours) (Cav) for PF-06651600 (Multiple Dose)
timeFrame: Days 1, 4, 6, 8, 10, 12 and 14 (0, 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48 hours post dose)
measure: Area Under the Curve for Dosing Interval (12 or 24 hours) for PF-06651600 (Multiple Dose)
timeFrame: Days 1, 4, 6, 8, 10, 12 and 14 (0, 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48 hours post dose)
measure: Dose Normalized Area Under the Curve for Dosing Interval (12 or 24 hours) for PF-06651600 (Multiple Dose)
timeFrame: Days 1, 4, 6, 8, 10, 12 and 14 (0, 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48 hours post dose)
measure: Peak to Trough Fluctuation (PTF) for PF-06651600 (Multiple Dose)
timeFrame: Days 1, 4, 6, 8, 10, 12 and 14 (0, 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48 hours post dose)
measure: Observed Accumulation Ratio (Rac) for PF-06651600 (Multiple Dose)
timeFrame: Days 1, 4, 6, 8, 10, 12 and 14 (0, 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48 hours post dose)
measure: Observed Accumulation Ratio for Cmax (RacCmax) for PF-06651600 (Multiple Dose)
timeFrame: Days 1, 4, 6, 8, 10, 12 and 14 (0, 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48 hours post dose)
measure: Steady State Accumulation Ratio (Rss) for PF-06651600 (Multiple Dose)
timeFrame: Days 1, 4, 6, 8, 10, 12 and 14 (0, 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48 hours post dose)
measure: Amount of PF-066561600 Excreted Unchanged (Multiple Dose)
timeFrame: Day 14 (12, 24 hours post dose)
measure: Change from baseline of BCL2 gene expression in whole blood (Single Dose)
timeFrame: Days -1 and 1 (0, 1, 2, 4, 8, 12 and 24 hours post dose)
measure: Change from baseline of BCL2 gene expression in whole blood (Multiple Dose)
timeFrame: Days 1, 5, 10, 14 (0, 1, 2, 4, 8, 12 and 24 hours post dose), 16, and 28
measure: Change from baseline of IP-10 protein concentration in serum (Multiple Dose)
timeFrame: Days 0, 2, 7, 14 (0, and 16 hours post dose) and 16
measure: Change from baseline of hsCRP protein concentration in serum (Multiple Dose)
timeFrame: Days 0, 2, 7, 14 (0, and 16 hours post dose) and 16
measure: Change from baseline of reticulocyte counts in whole blood (Single Dose)
timeFrame: Days 0, 2, 3, and 7
measure: Change from baseline of neutrophil counts in whole blood (Single Dose)
timeFrame: Days 0, 2, 3, and 7
measure: Change from baseline of hemoglobin level whole blood (Single Dose)
timeFrame: Days 0, 2, 3, and 7
measure: Change from baseline of reticulocyte counts in whole blood (Multiple Dose)
timeFrame: Days 0, 4, 8, 12, 14 (pre-dose) 15, and 28
measure: Change from baseline of neutrophil counts in whole blood (Multiple Dose)
timeFrame: Days 0, 4, 8, 12, 14 (pre-dose) 15, and 28
measure: Change from baseline of hemoglobin level in whole blood (Multiple Dose)
timeFrame: Days 0, 4, 8, 12, 14 (pre-dose) 15, and 28
measure: Renal Clearance (Multiple Dose)
timeFrame: Day 1, Day 14 (12, 24 hours post dose)
measure: Percentage of PF-066561600 Excreted Unchanged (Multiple Dose)
timeFrame: Day 14 (12, 24 hours post dose)
measure: Change from baseline of IP-10 gene expression in blood (Multiple Dose)
timeFrame: Days 0, 5, 10, 14 (0, 1, 2, 4, 8 and 12 hours post dose) and 16
measure: Change from baseline of IP-10 gene expression in blood (Single Dose)
timeFrame: Days 0, 1 (0, 1, 2, 4, 8 and 12 hours post dose) and 16
Other outcomes:
Locations:
city: Brussels
country: Belgium
facility: Pfizer Clinical Research Unit
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References:
citation: Telliez JB, Dowty ME, Wang L, Jussif J, Lin T, Li L, Moy E, Balbo P, Li W, Zhao Y, Crouse K, Dickinson C, Symanowicz P, Hegen M, Banker ME, Vincent F, Unwalla R, Liang S, Gilbert AM, Brown MF, Hayward M, Montgomery J, Yang X, Bauman J, Trujillo JI, Casimiro-Garcia A, Vajdos FF, Leung L, Geoghegan KF, Quazi A, Xuan D, Jones L, Hett E, Wright K, Clark JD, Thorarensen A. Discovery of a JAK3-Selective Inhibitor: Functional Differentiation of JAK3-Selective Inhibition over pan-JAK or JAK1-Selective Inhibition. ACS Chem Biol. 2016 Dec 16;11(12):3442-3451. doi: 10.1021/acschembio.6b00677. Epub 2016 Nov 10.