Healthy
Conditions
Keywords
Inflammatory bowel disease
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.
Interventions
PF-06651600 or placebo will be administered as an extemporaneously prepared solution in each cohort.
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 24 hour creatinine clearance (Single Dose) | Single dose period, Day 0 (baseline) and 24 hours post dose Day 1. | 24 hour urine creatinine clearance in healthy subjects participating in the single dose periods. For the single dose period, assessment occurs on Study Days 0 and 1. |
| 24 hour creatinine clearance (Multiple Dose) | Multiple dose period, Days 0 (baseline), 7 and 14. | 24 hour urine creatinine clearance in healthy subjects participating in the multiple dose period. For the multiple ascending dose period assessments occur on Study Days 7 and 14. |
| Change from baseline in urine volume (Single Dose) | Single dose period, Day 0 (baseline) and 24 hours post dose Day 1. | For the single dose period, assessment occurs on Study Days 0 and 1. |
| Change from baseline in urine electrolytes (Single Dose) | Single dose period, Day 0 (baseline) and 24 hours post dose Day 1. | For the single dose period, assessment occurs on Study Days 0 and 1. |
| Change from baseline in urine osmolality (Single Dose) | Single dose period, Day 0 (baseline) and 24 hours post dose Day 1. | For the single dose period, assessment occurs on Study Days 0 and 1. |
| Change from baseline of urine volume (Multiple Dose) | Multiple dose period, Days 0 (baseline), 7 and 14. | For the multiple ascending dose period assessments occur on Study Days 7 and 14. |
| Change from baseline of urine electrolytes (Multiple Dose) | Multiple dose period, Days 0 (baseline), 7 and 14. | For the multiple ascending dose period assessments occur on Study Days 7 and 14. |
| Change from baseline in urine osmolality (Multiple Dose) | Multiple dose period, Days 0 (baseline), 7 and 14. | For the multiple ascending dose period assessments occur on Study Days 7 and 14. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Dose Normalized Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinfdn) for PF-06651600 (Single Dose) | 0, 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, 48 hours post dose | Dose Normalized Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinfdn) |
| Dose Normalized Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClastdn) for PF-06651600 (Single Dose) | 0, 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, 48 hours post dose | Dose Normalized Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClastdn) |
| Plasma Decay Half-Life (t1/2) for PF-06651600 (Single Dose) | 0, 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, 48 hours post dose | Plasma Decay Half-Life (t1/2) |
| Plasma Decay Half-Life (t1/2) for PF-06651600 (Multiple Dose) | Days 1, 4, 6, 8, 10, 12 and 14 (0, 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48 hours post dose) | Plasma Decay Half-Life (t1/2) |
| Mean Resonance Time (MRT) for PF-06651600 (Single Dose) | 0, 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, 48 hours post dose | Mean Resonance Time (MRT) |
| Mean Resonance Time (MRT) for PF-06651600 (Multiple Dose) | Days 1, 4, 6, 8, 10, 12 and 14 (0, 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48 hours post dose) | Mean Resonance Time (MRT) |
| Apparent Volume of Distribution (Vz/F) for PF-06651600 (Single Dose) | 0, 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, 48 hours post dose | 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. |
| Apparent Volume of Distribution (Vz/F) for PF-06651600 (Multiple Dose) | Days 1, 4, 6, 8, 10, 12 and 14 (0, 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48 hours post dose) | 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. |
| Apparent Total Body Clearance (CL/F) for PF-06651600 (Single Dose) | 0, 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, 48 hours post dose | Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Apparent total body clearance (CL/F) is influenced by the fraction of the dose absorbed. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood. |
| Apparent Total Body Clearance (CL/F) for PF-06651600 (Multiple Dose) | Days 1, 4, 6, 8, 10, 12 and 14 (0, 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48 hours post dose) | Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Apparent total body clearance (CL/F) is influenced by the fraction of the dose absorbed. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood. |
| Minimum Observed Plasma Concentration (Cmin) for PF-06651600 (Multiple Dose) | Days 1, 4, 6, 8, 10, 12 and 14 (0, 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48 hours post dose) | Minimum Observed Plasma Concentration (Cmin) |
| Average Concentration for Dosing Interval (12 or 24 hours) (Cav) for PF-06651600 (Multiple Dose) | Days 1, 4, 6, 8, 10, 12 and 14 (0, 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48 hours post dose) | Average Concentration for Dosing Interval (12 or 24 hours) (Cav) |
| Area Under the Curve for Dosing Interval (12 or 24 hours) for PF-06651600 (Multiple Dose) | Days 1, 4, 6, 8, 10, 12 and 14 (0, 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48 hours post dose) | Area Under the Curve for Dosing Interval (12 or 24 hours) |
| Dose Normalized Area Under the Curve for Dosing Interval (12 or 24 hours) for PF-06651600 (Multiple Dose) | Days 1, 4, 6, 8, 10, 12 and 14 (0, 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48 hours post dose) | Dose Normalized Area Under the Curve for Dosing Interval (12 or 24 hours) |
| Peak to Trough Fluctuation (PTF) for PF-06651600 (Multiple Dose) | Days 1, 4, 6, 8, 10, 12 and 14 (0, 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48 hours post dose) | Peak to Trough Fluctuation (PTF) |
| Observed Accumulation Ratio (Rac) for PF-06651600 (Multiple Dose) | Days 1, 4, 6, 8, 10, 12 and 14 (0, 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48 hours post dose) | Observed Accumulation Ratio (Rac) |
| Observed Accumulation Ratio for Cmax (RacCmax) for PF-06651600 (Multiple Dose) | Days 1, 4, 6, 8, 10, 12 and 14 (0, 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48 hours post dose) | Observed Accumulation Ratio for Cmax (RacCmax) |
| Steady State Accumulation Ratio (Rss) for PF-06651600 (Multiple Dose) | Days 1, 4, 6, 8, 10, 12 and 14 (0, 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48 hours post dose) | Steady State Accumulation Ratio (Rss) |
| Amount of PF-066561600 Excreted Unchanged (Multiple Dose) | Day 14 (12, 24 hours post dose) | Concentration in urine. |
| Change from baseline of BCL2 gene expression in whole blood (Single Dose) | Days -1 and 1 (0, 1, 2, 4, 8, 12 and 24 hours post dose) | — |
| Change from baseline of BCL2 gene expression in whole blood (Multiple Dose) | Days 1, 5, 10, 14 (0, 1, 2, 4, 8, 12 and 24 hours post dose), 16, and 28 | — |
| Change from baseline of IP-10 protein concentration in serum (Multiple Dose) | Days 0, 2, 7, 14 (0, and 16 hours post dose) and 16 | — |
| Maximum Observed Plasma Concentration (Cmax) for PF-06651600 (Single Dose) | 0, 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, 48 hours post dose | Maximum Observed Plasma Concentration (Cmax) |
| Change from baseline of reticulocyte counts in whole blood (Single Dose) | Days 0, 2, 3, and 7 | — |
| Change from baseline of neutrophil counts in whole blood (Single Dose) | Days 0, 2, 3, and 7 | — |
| Change from baseline of hemoglobin level whole blood (Single Dose) | Days 0, 2, 3, and 7 | — |
| Change from baseline of reticulocyte counts in whole blood (Multiple Dose) | Days 0, 4, 8, 12, 14 (pre-dose) 15, and 28 | — |
| Change from baseline of neutrophil counts in whole blood (Multiple Dose) | Days 0, 4, 8, 12, 14 (pre-dose) 15, and 28 | — |
| Change from baseline of hemoglobin level in whole blood (Multiple Dose) | Days 0, 4, 8, 12, 14 (pre-dose) 15, and 28 | — |
| Renal Clearance (Multiple Dose) | Day 1, Day 14 (12, 24 hours post dose) | — |
| Percentage of PF-066561600 Excreted Unchanged (Multiple Dose) | Day 14 (12, 24 hours post dose) | Concentration in urine. |
| Change from baseline of IP-10 gene expression in blood (Multiple Dose) | Days 0, 5, 10, 14 (0, 1, 2, 4, 8 and 12 hours post dose) and 16 | — |
| Change from baseline of IP-10 gene expression in blood (Single Dose) | Days 0, 1 (0, 1, 2, 4, 8 and 12 hours post dose) and 16 | — |
| Change from baseline of hsCRP protein concentration in serum (Multiple Dose) | Days 0, 2, 7, 14 (0, and 16 hours post dose) and 16 | — |
| Maximum Observed Plasma Concentration (Cmax) for PF-06651600 (Multiple Dose) | Days 1, 4, 6, 8, 10, 12 and 14 (0, 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48 hours post dose) | Maximum Observed Plasma Concentration (Cmax) |
| Time to Reach Maximum Observed Plasma Concentration (Cmax) for PF-06651600 (Single Dose) | 0, 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, 48 hours post dose | Time to Reach Maximum Observed Plasma Concentration (Cmax) |
| Time to Reach Maximum Observed Plasma Concentration (Cmax) for PF-06651600 (Multiple Dose) | Days 1, 4, 6, 8, 10, 12 and 14 (0, 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48 hours post dose) | Time to Reach Maximum Observed Plasma Concentration (Cmax) |
| Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) for PF-06651600 (Single Dose) | 0, 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, 48 hours post dose | Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) |
| Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for PF-06651600 (Single Dose) | 0, 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, 48 hours post dose | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) |
| Dose Normalized Maximum Observed Plasma Concentration (Cmaxdn) for PF-06651600 (Single Dose) | 0, 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, 48 hours post dose | Dose Normalized Maximum Observed Plasma Concentration (Cmaxdn) |
| Dose Normalized Maximum Observed Plasma Concentration (Cmaxdn) for PF-06651600 (Multiple Dose) | Days 1, 4, 6, 8, 10, 12 and 14 (0, 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48 hours post dose) | Dose Normalized Maximum Observed Plasma Concentration (Cmaxdn) |
Countries
Belgium
Outcome results
None listed