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NCT Number: NCT02309827

Safety and Pharmacokinetic Study of PF-06651600 in Healthy Volunteers

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.

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Key information

Conditions

Healthy Digestive System Diseases Gastroenteritis Gastrointestinal Diseases Inflammatory Bowel Diseases Intestinal Diseases

Age range

18 year–55 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Pfizer Clinical Research Unit

Brussels, B-1070, Belgium

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

PF-06651600 or Placebo

Drug

PF-06651600 or placebo will be administered as an extemporaneously prepared solution in each cohort.

Primary outcomes

  1. 24 hour creatinine clearance (Single Dose)

    Time frame: 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.

  2. 24 hour creatinine clearance (Multiple Dose)

    Time frame: 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.

  3. Change from baseline in urine volume (Single Dose)

    Time frame: 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.

  4. Change from baseline in urine electrolytes (Single Dose)

    Time frame: 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.

  5. Change from baseline in urine osmolality (Single Dose)

    Time frame: 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.

  6. Change from baseline of urine volume (Multiple Dose)

    Time frame: Multiple dose period, Days 0 (baseline), 7 and 14.

    For the multiple ascending dose period assessments occur on Study Days 7 and 14.

  7. Change from baseline of urine electrolytes (Multiple Dose)

    Time frame: Multiple dose period, Days 0 (baseline), 7 and 14.

    For the multiple ascending dose period assessments occur on Study Days 7 and 14.

  8. Change from baseline in urine osmolality (Multiple Dose)

    Time frame: Multiple dose period, Days 0 (baseline), 7 and 14.

    For the multiple ascending dose period assessments occur on Study Days 7 and 14.

Secondary outcomes

  1. Maximum Observed Plasma Concentration (Cmax) for PF-06651600 (Single Dose)

    Time frame: 0, 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, 48 hours post dose

    Maximum Observed Plasma Concentration (Cmax)

  2. Maximum Observed Plasma Concentration (Cmax) for PF-06651600 (Multiple Dose)

    Time frame: 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)

  3. Time to Reach Maximum Observed Plasma Concentration (Cmax) for PF-06651600 (Single Dose)

    Time frame: 0, 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, 48 hours post dose

    Time to Reach Maximum Observed Plasma Concentration (Cmax)

  4. Time to Reach Maximum Observed Plasma Concentration (Cmax) for PF-06651600 (Multiple Dose)

    Time frame: 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)

  5. Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) for PF-06651600 (Single Dose)

    Time frame: 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)

  6. Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for PF-06651600 (Single Dose)

    Time frame: 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)

  7. Dose Normalized Maximum Observed Plasma Concentration (Cmaxdn) for PF-06651600 (Single Dose)

    Time frame: 0, 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, 48 hours post dose

    Dose Normalized Maximum Observed Plasma Concentration (Cmaxdn)

  8. Dose Normalized Maximum Observed Plasma Concentration (Cmaxdn) for PF-06651600 (Multiple Dose)

    Time frame: 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)

  9. Dose Normalized Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinfdn) for PF-06651600 (Single Dose)

    Time frame: 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)

  10. Dose Normalized Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClastdn) for PF-06651600 (Single Dose)

    Time frame: 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)

  11. Plasma Decay Half-Life (t1/2) for PF-06651600 (Single Dose)

    Time frame: 0, 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, 48 hours post dose

    Plasma Decay Half-Life (t1/2)

  12. Plasma Decay Half-Life (t1/2) for PF-06651600 (Multiple Dose)

    Time frame: 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)

  13. Mean Resonance Time (MRT) for PF-06651600 (Single Dose)

    Time frame: 0, 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, 48 hours post dose

    Mean Resonance Time (MRT)

  14. Mean Resonance Time (MRT) for PF-06651600 (Multiple Dose)

    Time frame: 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)

  15. Apparent Volume of Distribution (Vz/F) for PF-06651600 (Single Dose)

    Time frame: 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.

  16. Apparent Volume of Distribution (Vz/F) for PF-06651600 (Multiple Dose)

    Time frame: 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.

  17. Apparent Total Body Clearance (CL/F) for PF-06651600 (Single Dose)

    Time frame: 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.

  18. Apparent Total Body Clearance (CL/F) for PF-06651600 (Multiple Dose)

    Time frame: 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.

  19. Minimum Observed Plasma Concentration (Cmin) for PF-06651600 (Multiple Dose)

    Time frame: 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)

  20. Average Concentration for Dosing Interval (12 or 24 hours) (Cav) for PF-06651600 (Multiple Dose)

    Time frame: 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)

  21. Area Under the Curve for Dosing Interval (12 or 24 hours) for PF-06651600 (Multiple Dose)

    Time frame: 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)

  22. Dose Normalized Area Under the Curve for Dosing Interval (12 or 24 hours) for PF-06651600 (Multiple Dose)

    Time frame: 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)

  23. Peak to Trough Fluctuation (PTF) for PF-06651600 (Multiple Dose)

    Time frame: 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)

  24. Observed Accumulation Ratio (Rac) for PF-06651600 (Multiple Dose)

    Time frame: 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)

  25. Observed Accumulation Ratio for Cmax (RacCmax) for PF-06651600 (Multiple Dose)

    Time frame: 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)

  26. Steady State Accumulation Ratio (Rss) for PF-06651600 (Multiple Dose)

    Time frame: 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)

  27. Amount of PF-066561600 Excreted Unchanged (Multiple Dose)

    Time frame: Day 14 (12, 24 hours post dose)

    Concentration in urine.

  28. Change from baseline of BCL2 gene expression in whole blood (Single Dose)

    Time frame: Days -1 and 1 (0, 1, 2, 4, 8, 12 and 24 hours post dose)

  29. Change from baseline of BCL2 gene expression in whole blood (Multiple Dose)

    Time frame: Days 1, 5, 10, 14 (0, 1, 2, 4, 8, 12 and 24 hours post dose), 16, and 28

  30. Change from baseline of IP-10 protein concentration in serum (Multiple Dose)

    Time frame: Days 0, 2, 7, 14 (0, and 16 hours post dose) and 16

  31. Change from baseline of hsCRP protein concentration in serum (Multiple Dose)

    Time frame: Days 0, 2, 7, 14 (0, and 16 hours post dose) and 16

  32. Change from baseline of reticulocyte counts in whole blood (Single Dose)

    Time frame: Days 0, 2, 3, and 7

  33. Change from baseline of neutrophil counts in whole blood (Single Dose)

    Time frame: Days 0, 2, 3, and 7

  34. Change from baseline of hemoglobin level whole blood (Single Dose)

    Time frame: Days 0, 2, 3, and 7

  35. Change from baseline of reticulocyte counts in whole blood (Multiple Dose)

    Time frame: Days 0, 4, 8, 12, 14 (pre-dose) 15, and 28

  36. Change from baseline of neutrophil counts in whole blood (Multiple Dose)

    Time frame: Days 0, 4, 8, 12, 14 (pre-dose) 15, and 28

  37. Change from baseline of hemoglobin level in whole blood (Multiple Dose)

    Time frame: Days 0, 4, 8, 12, 14 (pre-dose) 15, and 28

  38. Renal Clearance (Multiple Dose)

    Time frame: Day 1, Day 14 (12, 24 hours post dose)

  39. Percentage of PF-066561600 Excreted Unchanged (Multiple Dose)

    Time frame: Day 14 (12, 24 hours post dose)

    Concentration in urine.

  40. Change from baseline of IP-10 gene expression in blood (Multiple Dose)

    Time frame: Days 0, 5, 10, 14 (0, 1, 2, 4, 8 and 12 hours post dose) and 16

  41. Change from baseline of IP-10 gene expression in blood (Single Dose)

    Time frame: Days 0, 1 (0, 1, 2, 4, 8 and 12 hours post dose) and 16

Sponsors and collaborators

Lead sponsor

Pfizer

Industry

Registry information

Official study 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

Important dates

Study start
2014
Primary completion
2016
Study completion
2016
First posted
Dec 5, 2014
Registry last updated
Sep 19, 2016

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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