Juvenile Idiopathic Arthritis
Conditions
Keywords
Arthritis, Pediatric, Tofacitinib, JIA
Brief summary
Phase 1 study to describe pharmacokinetics of CP-690,550 in pediatric patients 2 to less than 18 years of age with Juvenile Idiopathic Rheumatoid Arthritis (JIA).
Detailed description
This is an open-label, non-randomized, multi-center, oral CP-690,550, multiple-dose (twice daily for 5 days \[except Day 5 when only morning dose will be given\]) study in pediatric subjects with JIA aged from 2 to less than 18 years. Baseline visit will occur within 1 month of the completion of the Screening Visit. The study will consist of three cohorts based on the age of the subjects, Cohort 3: 2 to less than 6 years, Cohort 2: 6 to less than 12 years and Cohort 1: 12 to less than 18 years. In each cohort, at least 8 pediatric subjects with JIA will participate in the study ensuring a total number of at least 24 pediatric evaluable subjects completing the PK period.
Interventions
DRUGCP-690,550
CP-690,550 will be administered orally twice daily according to the dosing regimen provided below. Oral solution will be used for children weighing \<40 kg. Oral tablets will be used for children weighing ≥40 kg. Children aged 12 to less than 18 years who are unable to swallow tablets will have the option of taking oral solution. Body Weight (kg) Dose (mg) Volume (mL) 5-11 1 1; 12-18 1.5 1.5; 19-24 2 2; 25-31 2.5 2.5; 32-39 3 3; ≥40 5 5
Sponsors
Pfizer
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
2 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
1. Pediatric patients with JIA aged from 2 to less than 18 years with active JIA (extended oligoarthritis, polyarthritis rheumatoid factor positive or negative, psoriatic arthritis, enthesitis related arthritis), in 5 or more joints (using American College Rheumatology definition of active joint) at the time of the first study drug administration. 2. For subjects receiving MTX treatment, minimum duration of therapy is 4 months and dose stable for at least 6 weeks prior to first dose of study drug. MTX may be administered either orally or parenterally at doses not to exceed 20 mg/wk or 15 mg/m2/week. 3. A negative QuantiFERON-TB Gold In-Tube test performed within the 3 months prior to screening. A negative PPD test can be substituted for the QuantiFERON-TB Gold In-Tube test only if the central laboratory is unable to perform the test or cannot determine the results to be positive or negative and the Pfizer medical monitor approves it, on a case-by-case basis.
Exclusion criteria
1. Systemic JIA, persistent oligoarthritis, undifferentiated arthritis. 2. Current or recent history of uncontrolled clinically significant renal, hepatic, hematological, gastrointestinal, endocrine, pulmonary, cardiac, or neurological disease. 3. History of any other rheumatic autoimmune disease. 4. Infections: 1. Latent or active TB or any history of previous TB. 2. Chronic infections. 3. Any infection requiring hospitalization, parenteral antimicrobial therapy or judged to be opportunistic by the investigator within the 6 months prior to the first dose of study drug. 4. Any treated infections within 2 weeks of Baseline visit. 5. A subject known to be infected with human immunodeficiency virus (HIV), hepatitis B or hepatitis C virus. 6. History of infected joint prosthesis with prosthesis still in situ. 5. History of recurrent (more than one episode) herpes zoster or disseminated (a single episode) herpes zoster or disseminated (a single episode) herpes simplex. 6. The biologic agents and DMARDs are disallowed at any time during this study. If a subject needs to be treated with one of these agents, the subject should be discontinued from the study. 7. Subjects who have been vaccinated with live or attenuated vaccines within the 6 weeks prior to the first dose of study medication or is to be vaccinated with these vaccines at any time during treatment or within 6 weeks following discontinuation of study drug. 8. Subjects with a malignancy or with a history of malignancy with the exception of adequately treated or excised non-metastatic basal cell or squamous cell cancer of the skin or cervical carcinoma in situ.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Apparent Oral Clearance (CL/F) | Day 5: Pre-dose, 0.5, 1, 2, 4, 8 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. 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. |
| Number of Participants With Treatment-Emergent Adverse Events (AEs) All Causalities | Baseline up to 28 days after the last dose of study drug (Day 5) | An AE was any untoward medical occurrence attributed to study drug in a participant 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. |
| Number of Participants With Laboratory Test Abnormalities | Baseline up to Day 5 | Participants 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\>\</0\>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 \[HPF\]). |
| Number of Participants With Clinically Significant Vital Signs Abnormalities | Baseline up to Day 5 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Plasma Decay Half-Life (t1/2) | Day 5: Pre-dose, 0.5, 1, 2, 4, 8 hours post dose | Plasma decay half-life is the time measured for the plasma concentration to decrease by one half. |
| Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) | Day 5: Pre-dose, 0.5, 1, 2, 4, 8 hours post dose | — |
| Taste Assessment | Day 1, Day 5 | Participants were evaluated for taste assessment using a 5 categories questionnaire. Participants 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 participants who received the oral solution. Number of participants within each category are reported. |
| Maximum Observed Plasma Concentration (Cmax) | Day 5: Pre-dose, 0.5, 1, 2, 4, 8 hours post dose | — |
| Time to Reach Maximum Observed Plasma Concentration (Tmax) | Day 5: Pre-dose, 0.5, 1, 2, 4, 8 hours post dose | — |
| Apparent Volume of Distribution (Vz/F) | Day 5: Pre-dose, 0.5, 1, 2, 4, 8 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. |
Countries
Germany, Poland, Slovakia, United States
Participant flow
Pre-assignment details
Participants aged 2 to less than (\<)18 years with juvenile idiopathic arthritis (JIA) were enrolled in the study.
Participants by arm
| Arm | Count |
|---|---|
| Cohort I: 12 Years to <18 Years 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 participants weighing greater than or equal to (\>=) 40 kg. Participants who were unable to swallow tablets had the option of taking oral solution. | 8 |
| Cohort II: 6 Years to <12 Years CP-690,550 was administered orally, twice daily as oral solution (ranging from 1 mL to 3 mL) for participants weighing \<40 kg, oral tablets (5 mg) were used for participants weighing \>=40 kg. Participants with a body weight of \>=40 kg had the option of taking oral solution (5 mL) or tablets (5 mg). | 9 |
| Cohort III: 2 Years to <6 Years CP-690,550 was administered orally, twice daily as oral solution (ranging from 1 mL to 4.5 mL) for participants weighing \<30 kg. Participants weighing \>=30 kg had the option of taking oral solution (5 mL) or tablets (5 mg). | 9 |
| Total | 26 |
Baseline characteristics
| Characteristic | Cohort I: 12 Years to <18 Years | Cohort II: 6 Years to <12 Years | Cohort III: 2 Years to <6 Years | Total |
|---|---|---|---|---|
| Age, Continuous | 14.1 years STANDARD_DEVIATION 2 | 9.4 years STANDARD_DEVIATION 1.8 | 4.0 years STANDARD_DEVIATION 1 | 9.0 years STANDARD_DEVIATION 4.5 |
| Sex: Female, Male Female | 5 Participants | 5 Participants | 7 Participants | 17 Participants |
| Sex: Female, Male Male | 3 Participants | 4 Participants | 2 Participants | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 1 / 8 | 1 / 9 | 2 / 9 |
| serious Total, serious adverse events | 0 / 8 | 0 / 9 | 0 / 9 |
Outcome results
Primary
Apparent Oral Clearance (CL/F)
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.
Time frame: Day 5: Pre-dose, 0.5, 1, 2, 4, 8 hours post dose
Population: The PK analysis population included all enrolled and treated participants who had at least 1 of the PK parameters of primary interest. Here 'number of participants analyzed (N)' signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cohort I: 12 Years to <18 Years | Apparent Oral Clearance (CL/F) | 28.09 liter per hour | Geometric Coefficient of Variation 22 |
| Cohort II: 6 Years to <12 Years | Apparent Oral Clearance (CL/F) | 25.48 liter per hour | Geometric Coefficient of Variation 40 |
| Cohort III: 2 Years to <6 Years | Apparent Oral Clearance (CL/F) | 20.53 liter per hour | Geometric Coefficient of Variation 33 |
Primary
Number of Participants With Clinically Significant Vital Signs Abnormalities
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.
Time frame: Baseline up to Day 5
Population: The safety analysis population included all participants who received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort I: 12 Years to <18 Years | Number of Participants With Clinically Significant Vital Signs Abnormalities | 0 participants |
| Cohort II: 6 Years to <12 Years | Number of Participants With Clinically Significant Vital Signs Abnormalities | 0 participants |
| Cohort III: 2 Years to <6 Years | Number of Participants With Clinically Significant Vital Signs Abnormalities | 0 participants |
Primary
Number of Participants With Laboratory Test Abnormalities
Participants 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\>\</0\>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 \[HPF\]).
Time frame: Baseline up to Day 5
Population: The safety analysis population included all participants who received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort I: 12 Years to <18 Years | Number of Participants With Laboratory Test Abnormalities | 3 participants |
| Cohort II: 6 Years to <12 Years | Number of Participants With Laboratory Test Abnormalities | 1 participants |
| Cohort III: 2 Years to <6 Years | Number of Participants With Laboratory Test Abnormalities | 5 participants |
Primary
Number of Participants With Treatment-Emergent Adverse Events (AEs) All Causalities
An AE was any untoward medical occurrence attributed to study drug in a participant 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.
Time frame: Baseline up to 28 days after the last dose of study drug (Day 5)
Population: The safety analysis population included all participants who received at least 1 dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort I: 12 Years to <18 Years | Number of Participants With Treatment-Emergent Adverse Events (AEs) All Causalities | AE | 1 participants |
| Cohort I: 12 Years to <18 Years | Number of Participants With Treatment-Emergent Adverse Events (AEs) All Causalities | SAE | 0 participants |
| Cohort II: 6 Years to <12 Years | Number of Participants With Treatment-Emergent Adverse Events (AEs) All Causalities | AE | 1 participants |
| Cohort II: 6 Years to <12 Years | Number of Participants With Treatment-Emergent Adverse Events (AEs) All Causalities | SAE | 0 participants |
| Cohort III: 2 Years to <6 Years | Number of Participants With Treatment-Emergent Adverse Events (AEs) All Causalities | AE | 2 participants |
| Cohort III: 2 Years to <6 Years | Number of Participants With Treatment-Emergent Adverse Events (AEs) All Causalities | SAE | 0 participants |
Secondary
Apparent Volume of Distribution (Vz/F)
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.
Time frame: Day 5: Pre-dose, 0.5, 1, 2, 4, 8 hours post dose
Population: The PK analysis population included all enrolled and treated participants who had at least 1 of the PK parameters of primary interest. Here 'N' signifies those participants who were analyzed for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cohort I: 12 Years to <18 Years | Apparent Volume of Distribution (Vz/F) | 104.9 liter | Geometric Coefficient of Variation 35 |
| Cohort II: 6 Years to <12 Years | Apparent Volume of Distribution (Vz/F) | 71.0 liter | Geometric Coefficient of Variation 40 |
| Cohort III: 2 Years to <6 Years | Apparent Volume of Distribution (Vz/F) | 51.44 liter | Geometric Coefficient of Variation 34 |
Secondary
Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau)
Time frame: Day 5: Pre-dose, 0.5, 1, 2, 4, 8 hours post dose
Population: The PK analysis population included all enrolled and treated participants who had at least 1 of the PK parameters of primary interest. Here 'N' signifies those participants who were analyzed for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cohort I: 12 Years to <18 Years | Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) | 156.6 nanogram*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 25 |
| Cohort II: 6 Years to <12 Years | Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) | 118.8 nanogram*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 27 |
| Cohort III: 2 Years to <6 Years | Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) | 142.5 nanogram*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 32 |
Secondary
Maximum Observed Plasma Concentration (Cmax)
Time frame: Day 5: Pre-dose, 0.5, 1, 2, 4, 8 hours post dose
Population: The PK analysis population included all enrolled and treated participants who had at least 1 of the PK parameters of primary interest.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cohort I: 12 Years to <18 Years | Maximum Observed Plasma Concentration (Cmax) | 46.97 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 40 |
| Cohort II: 6 Years to <12 Years | Maximum Observed Plasma Concentration (Cmax) | 41.67 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 29 |
| Cohort III: 2 Years to <6 Years | Maximum Observed Plasma Concentration (Cmax) | 66.15 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 28 |
Secondary
Plasma Decay Half-Life (t1/2)
Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.
Time frame: Day 5: Pre-dose, 0.5, 1, 2, 4, 8 hours post dose
Population: The PK analysis population included all enrolled and treated participants who had at least 1 of the PK parameters of primary interest. Here 'N' signifies those participants who were analyzed for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort I: 12 Years to <18 Years | Plasma Decay Half-Life (t1/2) | 2.616 hours | Standard Deviation 0.454 |
| Cohort II: 6 Years to <12 Years | Plasma Decay Half-Life (t1/2) | 1.949 hours | Standard Deviation 0.294 |
| Cohort III: 2 Years to <6 Years | Plasma Decay Half-Life (t1/2) | 1.771 hours | Standard Deviation 0.406 |
Secondary
Taste Assessment
Participants were evaluated for taste assessment using a 5 categories questionnaire. Participants 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 participants who received the oral solution. Number of participants within each category are reported.
Time frame: Day 1, Day 5
Population: The analysis population was defined as all participants who had received at least 1 oral solution formulation of tofacitinib.
| Arm | Measure | Group | Value (NUMBER) | Dispersion |
|---|---|---|---|---|
| Cohort I: 12 Years to <18 Years | Taste Assessment | Day 5: Dislike a little | 1 participants | — |
| Cohort I: 12 Years to <18 Years | Taste Assessment | Day 1: Like a little | 1 participants | — |
| Cohort I: 12 Years to <18 Years | Taste Assessment | Day 1: Dislike a little | 0 participants | — |
| Cohort I: 12 Years to <18 Years | Taste Assessment | Day 5: Dislike very much | 0 participants | — |
| Cohort I: 12 Years to <18 Years | Taste Assessment | Day 1: Like very much | 0 participants | — |
| Cohort I: 12 Years to <18 Years | Taste Assessment | Day 5: Like very much | 0 participants | — |
| Cohort I: 12 Years to <18 Years | Taste Assessment | Day 1: Dislike very much | 0 participants | 0.4535 |
| Cohort I: 12 Years to <18 Years | Taste Assessment | Day 5: Not sure | 1 participants | — |
| Cohort I: 12 Years to <18 Years | Taste Assessment | Day 1: Not sure | 1 participants | — |
| Cohort I: 12 Years to <18 Years | Taste Assessment | Day 5: Like a little | 0 participants | — |
| Cohort II: 6 Years to <12 Years | Taste Assessment | Day 1: Like very much | 2 participants | — |
| Cohort II: 6 Years to <12 Years | Taste Assessment | Day 5: Like very much | 2 participants | — |
| Cohort II: 6 Years to <12 Years | Taste Assessment | Day 1: Dislike very much | 1 participants | 0.29396 |
| Cohort II: 6 Years to <12 Years | Taste Assessment | Day 1: Dislike a little | 0 participants | — |
| Cohort II: 6 Years to <12 Years | Taste Assessment | Day 1: Not sure | 1 participants | — |
| Cohort II: 6 Years to <12 Years | Taste Assessment | Day 1: Like a little | 3 participants | — |
| Cohort II: 6 Years to <12 Years | Taste Assessment | Day 5: Dislike very much | 1 participants | — |
| Cohort II: 6 Years to <12 Years | Taste Assessment | Day 5: Dislike a little | 0 participants | — |
| Cohort II: 6 Years to <12 Years | Taste Assessment | Day 5: Not sure | 2 participants | — |
| Cohort II: 6 Years to <12 Years | Taste Assessment | Day 5: Like a little | 2 participants | — |
| Cohort III: 2 Years to <6 Years | Taste Assessment | Day 1: Not sure | 1 participants | — |
| Cohort III: 2 Years to <6 Years | Taste Assessment | Day 5: Like very much | 3 participants | — |
| Cohort III: 2 Years to <6 Years | Taste Assessment | Day 5: Dislike a little | 3 participants | — |
| Cohort III: 2 Years to <6 Years | Taste Assessment | Day 1: Dislike a little | 2 participants | — |
| Cohort III: 2 Years to <6 Years | Taste Assessment | Day 5: Like a little | 2 participants | — |
| Cohort III: 2 Years to <6 Years | Taste Assessment | Day 5: Not sure | 1 participants | — |
| Cohort III: 2 Years to <6 Years | Taste Assessment | Day 1: Like very much | 4 participants | — |
| Cohort III: 2 Years to <6 Years | Taste Assessment | Day 1: Like a little | 1 participants | — |
| Cohort III: 2 Years to <6 Years | Taste Assessment | Day 1: Dislike very much | 1 participants | 0.40634 |
| Cohort III: 2 Years to <6 Years | Taste Assessment | Day 5: Dislike very much | 0 participants | — |
Secondary
Time to Reach Maximum Observed Plasma Concentration (Tmax)
Time frame: Day 5: Pre-dose, 0.5, 1, 2, 4, 8 hours post dose
Population: The PK analysis population included all enrolled and treated participants who had at least 1 of the PK parameters of primary interest.
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Cohort I: 12 Years to <18 Years | Time to Reach Maximum Observed Plasma Concentration (Tmax) | 0.750 hours | Full Range 25 |
| Cohort II: 6 Years to <12 Years | Time to Reach Maximum Observed Plasma Concentration (Tmax) | 1.00 hours | Full Range 27 |
| Cohort III: 2 Years to <6 Years | Time to Reach Maximum Observed Plasma Concentration (Tmax) | 0.500 hours | Full Range 32 |