Safety and Pharmacokinetic Study of PF-06651600 in Healthy Volunteers
- Conditions
- Healthy
- Interventions
- Drug: PF-06651600 or Placebo
- Registration Number
- NCT02309827
- Lead Sponsor
- Pfizer
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 80
- 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.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- Not specified
- Arm && Interventions
Group Intervention Description Cohort 2: PF-06651600 or Placebo PF-06651600 or Placebo Single ascending doses of PF-06651600 or placebo to evaluate safety, tolerability and PK. Cohort 5: PF-06651600 or Placebo PF-06651600 or Placebo Single ascending doses and multiple ascending doses of PF-06651600 or placebo to evaluate safety, tolerability and PK. Cohort 6: PF-06651600 or Placebo PF-06651600 or Placebo Single ascending doses and multiple ascending doses of PF-06651600 or placebo to evaluate safety, tolerability and PK. Cohort 9: PF-06651600 or Placebo PF-06651600 or Placebo Multiple ascending doses of PF-06651600 or placebo to evaluate safety, tolerability and PK. Cohort 8: PF-06651600 or Placebo PF-06651600 or Placebo Single ascending doses and multiple ascending doses of PF-06651600 or placebo to evaluate safety, tolerability and PK. Cohort 4: PF-06651600 or Placebo PF-06651600 or Placebo Single ascending doses and multiple ascending doses of PF-06651600 or placebo to evaluate safety, tolerability and PK. Cohort 7: PF-06651600 or Placebo PF-06651600 or Placebo Single ascending doses and multiple ascending doses of PF-06651600 or placebo to evaluate safety, tolerability and PK. Cohort 3: PF-06651600 or Placebo PF-06651600 or Placebo Single ascending doses and multiple ascending doses of PF-06651600 or placebo to evaluate safety, tolerability and PK. Cohort 1: PF-06651600 or Placebo PF-06651600 or Placebo Single ascending doses of PF-06651600 or placebo to evaluate safety, tolerability and PK.
- Primary Outcome Measures
Name Time Method 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.
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 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 (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.
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 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 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.
- Secondary Outcome Measures
Name Time Method 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)
Change from baseline of neutrophil counts in whole blood (Multiple Dose) Days 0, 4, 8, 12, 14 (pre-dose) 15, and 28 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)
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)
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)
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)
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 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)
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)
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)
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)
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.
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)
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 IP-10 protein concentration in serum (Multiple Dose) Days 0, 2, 7, 14 (0, and 16 hours post dose) and 16 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)
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.
Amount of PF-066561600 Excreted Unchanged (Multiple Dose) Day 14 (12, 24 hours post dose) Concentration in urine.
Change from baseline of reticulocyte counts in whole blood (Single Dose) Days 0, 2, 3, and 7 Percentage of PF-066561600 Excreted Unchanged (Multiple Dose) Day 14 (12, 24 hours post dose) Concentration in urine.
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)
Renal Clearance (Multiple Dose) Day 1, Day 14 (12, 24 hours post dose) 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 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 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.
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)
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)
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 hemoglobin level in whole blood (Multiple Dose) Days 0, 4, 8, 12, 14 (pre-dose) 15, and 28 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 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.
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)
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 reticulocyte counts in whole blood (Multiple Dose) Days 0, 4, 8, 12, 14 (pre-dose) 15, and 28 Change from baseline of hsCRP protein concentration in serum (Multiple Dose) Days 0, 2, 7, 14 (0, and 16 hours post dose) and 16
Trial Locations
- Locations (1)
Pfizer Clinical Research Unit
🇧🇪Brussels, Belgium