Clinical Trial Results:
An Open-Label Multiple Dose Study To Evaluate The Pharmacokinetics, Safety And Tolerability Of CP-690,550 In Pediatric Patients From 2 To Less Than 18 Years Of Age With Juvenile Idiopathic Arthritis (JIA)
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Summary
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EudraCT number |
2011-004914-40 |
Trial protocol |
PL HU SK IT |
Global end of trial date |
04 Dec 2015
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Results information
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Results version number |
v1(current) |
This version publication date |
13 Jul 2016
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First version publication date |
13 Jul 2016
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
A3921103
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT01513902 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Pfizer, Inc.
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Sponsor organisation address |
235 E 42nd Street, New York, United States, NY 10017
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Public contact |
Pfizer ClinicalTrials.gov Call Center, Pfizer Inc., 001 8007181021, ClinicalTrials.gov_Inquiries@pfizer.com
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Scientific contact |
Pfizer ClinicalTrials.gov Call Center, Pfizer Inc., 001 8007181021, ClinicalTrials.gov_Inquiries@pfizer.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
Yes
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EMA paediatric investigation plan number(s) |
EMEA-000576-PIP01-09 | ||
Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
03 May 2016
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
04 Dec 2015
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
To characterize the pharmacokinetic (PK) and safety of CP-690,550 following multiple oral doses in pediatric subjects (from 2 to less than 18 years) with active JIA.
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Protection of trial subjects |
The study was in compliance with the ethical principles derived from the Declaration of Helsinki and in compliance with all International Council on Harmonization (ICH) Good Clinical Practice (GCP) Guidelines. All the local regulatory requirements pertinent to safety of trial subjects were followed.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
06 Mar 2013
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Germany: 10
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Country: Number of subjects enrolled |
Poland: 10
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Country: Number of subjects enrolled |
Slovakia: 1
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Country: Number of subjects enrolled |
United States: 5
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Worldwide total number of subjects |
26
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EEA total number of subjects |
21
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
18
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Adolescents (12-17 years) |
8
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Adults (18-64 years) |
0
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
- | ||||||||||||
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Pre-assignment
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Screening details |
Subjects aged 2 to less than (<)18 years with juvenile idiopathic arthritis (JIA) were enrolled in the study. | ||||||||||||
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Period 1
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Period 1 title |
Overall Study (overall period)
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Is this the baseline period? |
Yes | ||||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||||||||
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Cohort I: 12 Years to <18 Years | ||||||||||||
Arm description |
CP-690,550 was administered orally, twice daily as oral solution (ranging from 1 milliliter [mL] to 3 mL) for children weighing <40 kilogram (kg) or twice daily as oral tablets (5 milligram [mg]) for subjects weighing greater than or equal to (>=) 40 kg. Subjects who were unable to swallow tablets had the option of taking oral solution. | ||||||||||||
Arm type |
Experimental | ||||||||||||
Investigational medicinal product name |
Tofacitinib
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Investigational medicinal product code |
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Other name |
CP-690,550
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Pharmaceutical forms |
Oral solution
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Routes of administration |
Oral use
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Dosage and administration details |
CP-690,550 was administered orally, twice daily as oral solution.
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Investigational medicinal product name |
Tofacitinib
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Investigational medicinal product code |
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Other name |
CP-690,550
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
CP-690,550 was administered orally, twice daily as oral tablet.
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Arm title
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Cohort II: 6 Years to <12 Years | ||||||||||||
Arm description |
CP-690,550 was administered orally, twice daily as oral solution (ranging from 1 mL to 3 mL) for subjects weighing <40 kg, oral tablets (5 mg) were used for subjects weighing >=40 kg. Subjects with a body weight of >=40 kg had the option of taking oral solution (5 mL) or tablets (5 mg). | ||||||||||||
Arm type |
Experimental | ||||||||||||
Investigational medicinal product name |
Tofacitinib
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Investigational medicinal product code |
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Other name |
CP-690,550
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Pharmaceutical forms |
Oral solution
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Routes of administration |
Oral use
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Dosage and administration details |
CP-690,550 was administered orally, twice daily as oral solution.
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Investigational medicinal product name |
Tofacitinib
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Investigational medicinal product code |
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Other name |
CP-690,550
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
CP-690,550 was administered orally, twice daily as oral tablet.
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Arm title
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Cohort III: 2 Years to <6 Years | ||||||||||||
Arm description |
CP-690,550 was administered orally, twice daily as oral solution (ranging from 1 mL to 4.5 mL) for subjects weighing <30 kg. Subjects weighing >=30 kg had the option of taking oral solution (5 mL) or tablets (5 mg). | ||||||||||||
Arm type |
Experimental | ||||||||||||
Investigational medicinal product name |
Tofacitinib
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Investigational medicinal product code |
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Other name |
CP-690,550
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Pharmaceutical forms |
Oral solution
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Routes of administration |
Oral use
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Dosage and administration details |
CP-690,550 was administered orally, twice daily as oral solution.
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Baseline characteristics reporting groups
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Reporting group title |
Cohort I: 12 Years to <18 Years
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Reporting group description |
CP-690,550 was administered orally, twice daily as oral solution (ranging from 1 milliliter [mL] to 3 mL) for children weighing <40 kilogram (kg) or twice daily as oral tablets (5 milligram [mg]) for subjects weighing greater than or equal to (>=) 40 kg. Subjects who were unable to swallow tablets had the option of taking oral solution. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Cohort II: 6 Years to <12 Years
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Reporting group description |
CP-690,550 was administered orally, twice daily as oral solution (ranging from 1 mL to 3 mL) for subjects weighing <40 kg, oral tablets (5 mg) were used for subjects weighing >=40 kg. Subjects with a body weight of >=40 kg had the option of taking oral solution (5 mL) or tablets (5 mg). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Cohort III: 2 Years to <6 Years
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Reporting group description |
CP-690,550 was administered orally, twice daily as oral solution (ranging from 1 mL to 4.5 mL) for subjects weighing <30 kg. Subjects weighing >=30 kg had the option of taking oral solution (5 mL) or tablets (5 mg). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Cohort I: 12 Years to <18 Years
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Reporting group description |
CP-690,550 was administered orally, twice daily as oral solution (ranging from 1 milliliter [mL] to 3 mL) for children weighing <40 kilogram (kg) or twice daily as oral tablets (5 milligram [mg]) for subjects weighing greater than or equal to (>=) 40 kg. Subjects who were unable to swallow tablets had the option of taking oral solution. | ||
Reporting group title |
Cohort II: 6 Years to <12 Years
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Reporting group description |
CP-690,550 was administered orally, twice daily as oral solution (ranging from 1 mL to 3 mL) for subjects weighing <40 kg, oral tablets (5 mg) were used for subjects weighing >=40 kg. Subjects with a body weight of >=40 kg had the option of taking oral solution (5 mL) or tablets (5 mg). | ||
Reporting group title |
Cohort III: 2 Years to <6 Years
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Reporting group description |
CP-690,550 was administered orally, twice daily as oral solution (ranging from 1 mL to 4.5 mL) for subjects weighing <30 kg. Subjects weighing >=30 kg had the option of taking oral solution (5 mL) or tablets (5 mg). | ||
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End point title |
Apparent Oral Clearance (CL/F) [1] | ||||||||||||||||
End point description |
Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is also influenced by the fraction of the dose absorbed. Clearance was estimated by non compartmental analysis (NCA) of PK data. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood. It was calculated by dividing the given oral dose by AUCtau. AUCtau is the area under the plasma concentration time-curve from time zero to end of dosing interval. The PK analysis population included all enrolled and treated subjects who had at least 1 of the PK parameters of primary interest. Here 'number of subjects analyzed (N)' signifies those subjects who were evaluable for this outcome measure.
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End point type |
Primary
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End point timeframe |
Day 5: Pre-dose, 0.5, 1, 2, 4, 8 hours post dose
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Only descriptive data was planned to be reported for this endpoint |
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| No statistical analyses for this end point | |||||||||||||||||
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End point title |
Number of Subjects With Treatment-Emergent Adverse Events (AEs) All Causalities [2] | ||||||||||||||||||||
End point description |
An AE was any untoward medical occurrence attributed to study drug in a subject who received study drug. A serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment emergent AEs included both serious and non-serious AEs. The safety analysis population included all subjects who received at least 1 dose of study drug.
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End point type |
Primary
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End point timeframe |
Baseline up to 28 days after the last dose of study drug (Day 5)
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| Notes [2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Only descriptive data was planned to be reported for this endpoint |
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| No statistical analyses for this end point | |||||||||||||||||||||
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End point title |
Number of Subjects With Laboratory Test Abnormalities [3] | ||||||||||||
End point description |
Subjects with laboratory test abnormalities of potential clinical concern without regard to baseline abnormality were reported. Criteria: Hematology(hemoglobin,hematocrit,red blood cell[RBC] count:<0.8*lower limit of normal [LLN], platelets:<0.5*LLN/greater than [>]1.75*upper limit of normal[ULN], white blood cell [WBC] count:<0.6*LLN/ >1.5*ULN, lymphocytes, total neutrophils: <0.8*LLN or >1.2*ULN, basophils, eosinophil, monocytes:>1.2*ULN); Liver Function (total bilirubin: >1.5*ULN, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase:>3.0*ULN, total protein, albumin:<0.8*LLN or >1.2*ULN);Renal Function (blood urea nitrogen, creatinine:>1.3*ULN, uric acid:>1.2*ULN);Electrolytes (sodium:<0.95*LLN or >1.05*ULN,potassium,chloride,calcium,bicarbonate:<0.9*LLN or >1.1*ULN); Clinical chemistry (glucose <0.6*LLN or >1.5*ULN, creatine kinase:>3.0*ULN); Urinalysis (Urine WBC and RBC: greater than or equal to [>=] 6/High Power Field [HPF]).
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End point type |
Primary
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End point timeframe |
Baseline up to Day 5
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| Notes [3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Only descriptive data was planned to be reported for this endpoint |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Number of Subjects With Clinically Significant Vital Signs Abnormalities [4] | ||||||||||||
End point description |
Criteria for vital signs of potentially clinical concern included supine/sitting pulse rate of <40 beats per minute (bpm) or >120 bpm, standing pulse rate of <40 bpm or >140 bpm, systolic blood pressure of >=30 millimeters of mercury (mmHg) change from baseline and systolic blood pressure <90 mmHg, diastolic blood pressure >=20 mmHg change from baseline and diastolic blood pressure <50 mm Hg. The safety analysis population included all subjects who received at least 1 dose of study drug.
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End point type |
Primary
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End point timeframe |
Baseline up to Day 5
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| Notes [4] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Only descriptive data was planned to be reported for this endpoint |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Area Under the Curve From Time Zero to end of Dosing Interval (AUCtau) | ||||||||||||||||
End point description |
The PK analysis population included all enrolled and treated subjects who had at least 1 of the PK parameters of primary interest. Here 'number of subjects analyzed (N)' signifies those subjects who were evaluable for this outcome measure.
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End point type |
Secondary
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End point timeframe |
Day 5: Pre-dose, 0.5, 1, 2, 4, 8 hours post dose
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| No statistical analyses for this end point | |||||||||||||||||
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End point title |
Maximum Observed Plasma Concentration (Cmax) | ||||||||||||||||
End point description |
The PK analysis population included all enrolled and treated subjects who had at least 1 of the PK parameters of primary interest.
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End point type |
Secondary
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End point timeframe |
Day 5: Pre-dose, 0.5, 1, 2, 4, 8 hours post dose
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| No statistical analyses for this end point | |||||||||||||||||
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End point title |
Time to Reach Maximum Observed Plasma Concentration (Tmax) | ||||||||||||||||
End point description |
The PK analysis population included all enrolled and treated subjects who had at least 1 of the PK parameters of primary interest.
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End point type |
Secondary
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End point timeframe |
Day 5: Pre-dose, 0.5, 1, 2, 4, 8 hours post dose
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| No statistical analyses for this end point | |||||||||||||||||
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End point title |
Plasma Decay Half-Life (t1/2) | ||||||||||||||||
End point description |
Plasma decay half-life is the time measured for the plasma concentration to decrease by one half. The PK analysis population included all enrolled and treated subjects who had at least 1 of the PK parameters of primary interest. Here 'N' signifies those subjects who were evaluable for this outcome measure.
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End point type |
Secondary
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End point timeframe |
Day 5: Pre-dose, 0.5, 1, 2, 4, 8 hours post dose
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| No statistical analyses for this end point | |||||||||||||||||
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End point title |
Taste Assessment | ||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Subjects were evaluated for taste assessment using a 5 categories questionnaire. Subjects were asked to answer one of the following to describe the taste of oral solution of tofacitinib: Dislike very much, dislike a little, not sure, like a little, or like very much. The taste assessment was only performed for subjects who received the oral solution. Number of subjects within each category are reported. The analysis population was defined as all participants who had received at least 1 oral solution formulation of tofacitinib.
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End point type |
Secondary
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End point timeframe |
Day 1, Day 5
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||||||||||||||||
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End point title |
Apparent Volume of Distribution (Vz/F) | ||||||||||||||||
End point description |
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. The PK analysis population included all enrolled and treated subjects who had at least 1 of the PK parameters of primary interest. Here 'N' signifies those subjects who were evaluable for this outcome measure
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End point type |
Secondary
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End point timeframe |
Day 5: Pre-dose, 0.5, 1, 2, 4, 8 hours post dose
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| No statistical analyses for this end point | |||||||||||||||||
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Adverse events information
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Timeframe for reporting adverse events |
Baseline up to 28 days after the last dose of study drug (Day 5)
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Assessment type |
Non-systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
18.1
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Reporting groups
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Reporting group title |
Cohort I: 12 Years to <18 Years
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Reporting group description |
CP-690,550 was administered orally, twice daily as oral solution (ranging from 1 milliliter [mL] to 3 mL) for children weighing <40 kilogram (kg) or twice daily as oral tablets (5 milligram [mg]) for subjects weighing greater than or equal to (>=) 40 kg. Subjects who were unable to swallow tablets had the option of taking oral solution. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Cohort III: 2 Years to <6 Years
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Reporting group description |
CP-690,550 was administered orally, twice daily as oral solution (ranging from 1 mL to 4.5 mL) for subjects weighing <30 kg. Subjects weighing >=30 kg had the option of taking oral solution (5 mL) or tablets (5 mg). | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Cohort II: 6 Years to <12 Years
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Reporting group description |
CP-690,550 was administered orally, twice daily as oral solution (ranging from 1 mL to 3 mL) for subjects weighing <40 kg, oral tablets (5 mg) were used for subjects weighing >=40 kg. Subjects with a body weight of >=40 kg had the option of taking oral solution (5 mL) or tablets (5 mg). | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 0% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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30 Jan 2012 |
Add certain prohibited treatment for psoriases, added apparent volume of distribution (Vz/F) to the parameters to be analyzed. |
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02 Nov 2012 |
Exclusion criteria on lymphocytes levels added, section on infections added. |
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14 Jul 2014 |
Revision of dosing scheme |
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Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
