Clinical trial NCT01736696: Multiple Dose Escalation Study In Medically Stable Subjects With Psoriasis
Official title: Phase 1, Investigator-Blind, Subject-Blind, Sponsor-Open, Placebo-Controlled, Two-Week, Multiple Dose Escalation Study In Medically Stable Subjects With Psoriasis To Evaluate The Safety, Tolerability, Pharmacokinetics And Pharmacodynamics Of CP-690,550
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Psoriasis
Immunomodulation
Keywords: Psoriasis
PASI
plaques
skin biopsy
immunomodulation
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2012-11-29
Enrollment: 59
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study was conducted in subjects with psoriasis to evaluate drug activity in this patient population by analysis of changes in psoriatic lesion biopsy characteristics. This subject population was selected to evaluate potentially relevant biological activity of CP-690,550 as well as assessing safety and pharmacokinetics.


Eligibility criteria: Inclusion Criteria:

* Male and/or female subjects between the ages of 18 and 65 years, inclusive, with active psoriasis lesion(s).
* Subjects should be healthy with the exception of psoriasis, where healthy is defined as no clinically relevant abnormalities identified by a detailed medical history, full physical examination. Blood pressure must be \< 140/89. Body Mass Index (BMI) between 18-36 kg/m2, inclusive; and a total body weight \>50 kg (110 lbs)
* The following laboratory variables must be no more than 10% below the lower limit of the normal reference range: RBC, hemoglobin, hematocrit, WBC, absolute neutrophil count. The absolute lymphocyte count must be greater than or equal to the lower limit of the reference range. Values for AST, ALT, bilirubin and alkaline phosphatase must be no more than 10% above the upper limit of the normal reference range. Values for total cholesterol and LDL must be no more than 20% above the upper limit of the normal reference range except for subjects being treated for hyperlipidemia. Normal glomerular filtration rate (\> 80 mL/min).

Exclusion Criteria:

* Subjects with evidence or history of clinically significant hematological, renal, urological, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic disorder.
* Subjects with controlled essential hypertension and/or hyperlipidemia may be eligible for the study provided that any medications that are administered.
* Screening 12-lead ECG demonstrating at least one of the following: heart rate \> 100 bpm, QRS \>120 msec, QTc \> 430 msec (males), QTc \> 450 msec (females) or PR \> 220 msec.
* Abnormal chest radiographs including, but not limited to, evidence of past or present tuberculosis infection. History of tuberculosis without treatment and/or positive tuberculin reaction without known vaccination with BCG.
* Subjects with a history of tumors with the exception of adequately treated basal cell carcinoma of the skin.

Primary outcomes:
measure: Change From Baseline in QT Interval at 1 Hour Post Morning Dose (HPD 1) on Day 1
timeFrame: 23 hours (hrs) prior to morning dose on Day 1 (Baseline for HPD 1), 1 hour (hr) post morning dose on Day 1
measure: Change From Baseline in QT Interval at 2 Hour Post Morning Dose (HPD 2) on Day 1
timeFrame: 22 hrs prior to morning dose on Day 1 (Baseline for HPD 2), 2 hrs post morning dose on Day 1
measure: Change From Baseline in QT Interval at 4 Hour Post Morning Dose (HPD 4) on Day 1
timeFrame: 20 hrs prior to morning dose on Day 1 (Baseline for HPD 4), 4 hrs post morning dose on Day 1
measure: Change From Baseline in QT Interval at 8 Hour Post Morning Dose (HPD 8) on Day 1
timeFrame: 16 hrs prior to morning dose on Day 1 (Baseline for HPD 8), 8 hrs post morning dose on Day 1
measure: Change From Baseline in QT Interval at 12 Hour Post Morning Dose (HPD 12) on Day 1
timeFrame: 12 hrs prior to morning dose on Day 1 (Baseline for HPD 12), 12 hrs post morning dose on Day 1
measure: Change From Baseline in QT Interval at 16 Hour Post Morning Dose (HPD 16) on Day 1
timeFrame: 8 hrs prior to morning dose on Day 1 (Baseline for HPD 16), 16 hrs post morning dose on Day 1
measure: Change From Baseline in QT Interval at 0 Hour Post Morning Dose (HPD 0) on Day 14
timeFrame: Hour 0 (pre-dose) on Day 1 (Baseline for HPD 0), 0 hr on Day 14
measure: Change From Baseline in QT Interval at 1 Hour Post Morning Dose (HPD 1) on Day 14
timeFrame: 23 hrs prior to morning dose on Day 1 (Baseline for HPD 1), 1 hr post morning dose on Day 14
measure: Change From Baseline in QT Interval at 2 Hour Post Morning Dose (HPD 2) on Day 14
timeFrame: 22 hrs prior to morning dose on Day 1 (Baseline for HPD 2), 2 hrs post morning dose on Day 14
measure: Change From Baseline in QT Interval at 4 Hour Post Morning Dose (HPD 4) on Day 14
timeFrame: 20 hrs prior to morning dose on Day 1 (Baseline for HPD 4), 4 hrs post morning dose on Day 14
measure: Change From Baseline in QT Interval at 8 Hour Post Morning Dose (HPD 8) on Day 14
timeFrame: 16 hrs prior to morning dose on Day 1 (Baseline for HPD 8), 8 hrs post morning dose on Day 14
measure: Change From Baseline in QT Interval at 12 Hour Post Morning Dose (HPD 12) on Day 14
timeFrame: 12 hrs prior to morning dose on Day 1 (Baseline for HPD 12), 12 hrs post morning dose on Day 14
measure: Number of Participants With Increase From Baseline in Corrected QT (QTc) Interval
timeFrame: 1, 2, 4, 8, 12 hrs post dose, additional 16 hrs post dose for 60 mg once daily group on Day 1; 1, 2 hrs post dose on Day 4, 7, 10;1,2,4,8,12 hrs post dose on Day 14; Day 21
measure: Number of Participants With Corrected QT (QTc) Interval Greater Than or Equal to 500 Millisecond
timeFrame: 1, 2, 4, 8, 12 hrs post dose, additional 16 hrs post dose for 60 mg once daily group on Day 1; 1, 2 hrs post dose on Day 4, 7, 10;1,2,4,8,12 hrs post dose on Day 14; Day 21
measure: Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) at Day 1
timeFrame: 0 (pre-dose), 0.25, 0.5, 1, 2, 3, 4, 8, 12 hrs post dose on Day 1
measure: Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) at Day 14
timeFrame: 0 (pre-dose), 0.25, 0.5, 1, 2, 3, 4, 8, 12 hrs post dose on Day 14
measure: Maximum Observed Plasma Concentration (Cmax) at Day 1
timeFrame: 0 (pre-dose), 0.25, 0.5, 1, 2, 3, 4, 8, 12 hrs post dose on Day 1
measure: Maximum Observed Plasma Concentration (Cmax) at Day 14
timeFrame: 0 (pre-dose), 0.25, 0.5, 1, 2, 3, 4, 8, 12 hrs post dose on Day 14
measure: Time to Reach Maximum Observed Plasma Concentration (Tmax) at Day 1
timeFrame: 0 (pre-dose), 0.25, 0.5, 1, 2, 3, 4, 8, 12 hrs post dose on Day 1
measure: Time to Reach Maximum Observed Plasma Concentration (Tmax) at Day 14
timeFrame: 0 (pre-dose), 0.25, 0.5, 1, 2, 3, 4, 8, 12 hrs post dose on Day 14
measure: Accumulation Ratio (R0)
timeFrame: 0 (pre-dose), 0.25, 0.5, 1, 2, 3, 4, 8, 12 hrs post dose on Day 1 and Day 14
measure: Percent Change From Baseline in Fluorescence-Activated Cell Sorting (FACS) Analysis at Day 1
timeFrame: Baseline, 1 hr post-dose on Day 1
measure: Percent Change From Baseline in Fluorescence-Activated Cell Sorting (FACS) Analysis at Day 2
timeFrame: Baseline, hr 0 on Day 2
measure: Percent Change From Baseline in Fluorescence-Activated Cell Sorting (FACS) Analysis at Day 4
timeFrame: Baseline, hr 0 on Day 4
measure: Percent Change From Baseline in Fluorescence-Activated Cell Sorting (FACS) Analysis at Day 7
timeFrame: Baseline, hr 0 on Day 7
measure: Percent Change From Baseline in Fluorescence-Activated Cell Sorting (FACS) Analysis at Day 10
timeFrame: Baseline, hr 0 on Day 10
measure: Percent Change From Baseline in Fluorescence-Activated Cell Sorting (FACS) Analysis at Day 14
timeFrame: Baseline; hr 0, 8 hr post-dose on Day 14
measure: Percent Change From Baseline in Fluorescence-Activated Cell Sorting (FACS) Analysis at Day 18
timeFrame: Baseline, Hour 0 on Day 18
measure: Percent Change From Baseline in Fluorescence-Activated Cell Sorting (FACS) Analysis at Day 21
timeFrame: Baseline, hr 0 on Day 21
measure: Percent Change From Baseline in Fluorescence-Activated Cell Sorting (FACS) Analysis at Day 28
timeFrame: Baseline, hr 0 on Day 28
measure: Percent Change From Baseline in Fluorescence-Activated Cell Sorting (FACS) Analysis at Day 42
timeFrame: Baseline, hr 0 on Day 42
measure: Change From Baseline in Immune Cell Function at Day 14
timeFrame: Baseline (Within 7 days prior to Day 1), Day 14
measure: Change From Baseline in Reticulocyte Count at Day 2
timeFrame: Baseline (Within 7 days prior to Day 1), Day 2
measure: Change From Baseline in Reticulocyte Count at Day 4
timeFrame: Baseline (Within 7 days prior to Day 1), Day 4
measure: Change From Baseline in Reticulocyte Count at Day 7
timeFrame: Baseline (Within 7 days prior to Day 1), Day 7
measure: Change From Baseline in Reticulocyte Count at Day 10
timeFrame: Baseline (Within 7 days prior to Day 1), Day 10
measure: Change From Baseline in Reticulocyte Count at Day 15
timeFrame: Baseline (Within 7 days prior to Day 1), Day 15
measure: Change From Baseline in Reticulocyte Count at Day 21
timeFrame: Baseline (Within 7 days prior to Day 1), Day 21
measure: Change From Baseline in Reticulocyte Count at Day 28
timeFrame: Baseline (Within 7 days prior to Day 1), Day 28
measure: Change From Baseline in Reticulocyte Count at Day 42
timeFrame: Baseline (Within 7 days prior to Day 1), Day 42
measure: Time to Reach Maximum Change From Baseline and Time to Return to Baseline Value for Fluorescence-Activated Cell Sorting (FACS), Reticulocyte Counts and Immune Cell Function
timeFrame: Day 0 (pre-dose), 1, 2, 4, 7, 10, 14, 15, 18, 21, 28, 42
measure: Half Maximal Effective Area Under the Concentration-Time Curve 50 (EAUC 50)
timeFrame: Day 14
Secondary outcomes:
measure: Number of Participants With Modified Psoriasis Severity Index (mPASI) at Day 14
timeFrame: Baseline (Within 7 days prior to Day 1) up to Day 14
measure: Number of Participants With Physician's Global Assessment (PGA) of Psoriasis
timeFrame: Baseline (Within 7 days prior to Day 1) up to Day 14
measure: Gene Expression in Psoriatic Plaque Biopsies
timeFrame: Day 14
measure: Immunohistochemistry From Psoriatic Plaque Biopsies
timeFrame: Baseline (within 7 days prior to Day 1), Day 14
measure: Number of Participants With Keratin 16 (K16) Expression
timeFrame: Baseline (within 7 days prior to Day 1) up to Day 14
measure: Number of Participants With Intracellular Adhesion Molecule (ICAM-1) by Epidermal Keratinocytes Expression
timeFrame: Baseline (within 7 days prior to Day 1) up to Day 14
measure: Gene Expression in Peripheral Blood
timeFrame: Day 14
Other outcomes:
Locations:
city: Little Rock
country: United States
facility: Pfizer Investigational Site
state: Arkansas
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: