Cystic Fibrosis
Conditions
Brief summary
The purpose of this study was to evaluate the safety of ivacaftor treatment, and PK of ivacaftor and metabolites in participants with cystic fibrosis (CF) who are \<24 months of age at treatment initiation and have an ivacaftor-responsive CF transmembrane conductance regulator (CFTR) gene mutation.
Interventions
DRUGIVA
Granules in sachet for oral administration.
Sponsors
Vertex Pharmaceuticals Incorporated
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
1 Months to 24 Months
Healthy volunteers
No
Inclusion criteria
* Confirmed diagnosis of CF by sweat chloride value or CF mutation criteria. * Have 1 of the following 10 CFTR mutations on at least 1 allele: G551D, G178R, S549N, S549R, G551S, G1244E, S1251N, S1255P, G1349D or R117H (eligible in regions where ivacaftor is approved for use). Part A/B group may also have other ivacaftor-responsive mutations. * Hematology, serum chemistry, and vital signs results at screening with no clinically significant abnormalities that would interfere with the study assessments, as judged by the investigator.
Exclusion criteria
* History of any illness or condition that, in the opinion of the investigator, might confound the results of the study or pose an additional risk in administering study drug to the participant * Colonization with organisms associated with a more rapid decline in pulmonary status at screening (Only for Parts A and B) * History of abnormal liver function or abnormal liver function at screening * History of solid organ or hematological transplantation * Use of any moderate or strong inducers or inhibitors of cytochrome P450 (CYP) 3A within 2 weeks before Day 1 * Participation in a clinical study involving administration of either an investigational or a marketed drug within 30 days or 5 terminal half-lives before screening * Hemoglobin (Hgb) \<9.5 g/dL at screening * Chronic kidney disease of Stage 3 or above * Presence of a non-congenital or progressive lens opacity or cataract at Screening Other protocol defined Inclusion/
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Part A: Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious (TEAEs) | Day 1 through Day 70 |
| Part A: Observed Plasma Concentration of IVA and Their Metabolites (M1-IVA and M6-IVA) | Pre-dose, 2-4 hours, 6-8 hours, 24-60 hours post-dose |
| Part B +A/B: Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious (TEAEs) | Day 1 through Week 38 |
| Part A/B: Observed Plasma Concentration of IVA and Their Metabolites (M1-IVA and M6-IVA) | Day 4 (pre-dose, 2-4 hours, 6-8 hours post-dose); Day 15 (pre-dose); Week 4 (pre-dose); Week 8 (pre-dose, 2-4 hours, 6-8 hours post-dose); Week 12 (pre-dose); Week 18 (pre-dose) and Week 24 (pre-dose) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part B: Observed Plasma Concentration of IVA and Their Metabolites (M1-IVA and M6-IVA) | Week 2 (pre-dose, 2-4 hours, 6-8 hours post-dose); Week 8 (pre-dose,1 hour, 4-hour post-dose); Week 24 (pre-dose, 2-4 hours post dose) | — |
| Part B + A/B: Absolute Change From Baseline in Sweat Chloride | From Baseline at Week 24 | Sweat samples were collected using an approved collection device. |
Countries
Australia, Canada, Ireland, United Kingdom, United States
Participant flow
Recruitment details
This study was conducted in participants with cystic fibrosis (CF) who were less than (\<) 24 months of age at Day 1 and have an ivacaftor-responsive CF transmembrane conductance regulator (CFTR) mutation.
Participants by arm
| Arm | Count |
|---|---|
| Ivacaftor (IVA) Part A: Participants weighing 5 to \<7 kg received 25 mg IVA, 7 to \<14 kg received 50 mg IVA, and those weighing 14 to \<25 kg received 75 mg IVA administered q12h on Days 1 through 3 and 1 morning dose on Day 4.
Participants 4 to \<6 months of age and ≥5 kg received 25 mg IVA q12h. At 6 months of age and older, participants weighing 5 to \<7 kg received 25 mg IVA, 7 to \<14 kg received 50 mg IVA, and those weighing 14 to \<25 kg received 75 mg IVA q12h for 24 weeks on Part B.
For Part A/B, participants 1 to \<4 months weighing 3 kg to \<5 kg received an initial low dose of 5.7 mg q12h IVA and those weighing ≥5 kg received 11.4 mg q12h IVA for the first 15 days of IVA treatment. Doses were maintained or adjusted upward at Day 15 and based on weight and/or age once they reached 4 months of age. | 57 |
| Total | 57 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Part B + A/B ( Up to 24 Weeks) | Lost to Follow-up | 0 | 1 |
| Part B + A/B ( Up to 24 Weeks) | Physician Decision | 0 | 1 |
| Part B + A/B ( Up to 24 Weeks) | Withdrawal of Consent (not due to adverse event) | 0 | 1 |
Baseline characteristics
| Characteristic | Ivacaftor (IVA) |
|---|---|
| Age, Customized Part A 12 to <24 months | 7 Participants |
| Age, Customized Part A 1 to <4 months | 2 Participants |
| Age, Customized Part A 4 to <6 months | 4 Participants |
| Age, Customized Part A 6 to <12 months | 6 Participants |
| Age, Customized Part B+ A/B 12 to <24 months | 19 Participants |
| Age, Customized Part B+ A/B 1 to <4 months | 7 Participants |
| Age, Customized Part B+ A/B 4 to <6 months | 6 Participants |
| Age, Customized Part B+ A/B 6 to <12 months | 11 Participants |
| Race/Ethnicity, Customized Part A American Indian or Alaska Native | 0 Participants |
| Race/Ethnicity, Customized Part A Asian | 0 Participants |
| Race/Ethnicity, Customized Part A Black or African American | 0 Participants |
| Race/Ethnicity, Customized Part A Hispanic or Latino | 0 Participants |
| Race/Ethnicity, Customized Part A Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race/Ethnicity, Customized Part A Not collected per local regulations | 0 Participants |
| Race/Ethnicity, Customized Part A Not collected per local Regulations | 0 Participants |
| Race/Ethnicity, Customized Part A Not Hispanic or Latino | 19 Participants |
| Race/Ethnicity, Customized Part A White | 19 Participants |
| Race/Ethnicity, Customized Part B + A/B American Indian or Alaska Native | 0 Participants |
| Race/Ethnicity, Customized Part B + A/B Asian | 0 Participants |
| Race/Ethnicity, Customized Part B + A/B Black or African American | 0 Participants |
| Race/Ethnicity, Customized Part B + A/B Hispanic or Latino | 1 Participants |
| Race/Ethnicity, Customized Part B + A/B Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race/Ethnicity, Customized Part B + A/B Not collected per local regulations | 0 Participants |
| Race/Ethnicity, Customized Part B + A/B Not collected per local Regulations | 0 Participants |
| Race/Ethnicity, Customized Part B + A/B Not Hispanic or Latino | 42 Participants |
| Race/Ethnicity, Customized Part B + A/B White | 43 Participants |
| Sex: Female, Male Part A Female | 10 Participants |
| Sex: Female, Male Part A Male | 9 Participants |
| Sex: Female, Male Part B + A/B Female | 22 Participants |
| Sex: Female, Male Part B + A/B Male | 21 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 19 | 0 / 43 |
| other Total, other adverse events | 10 / 19 | 34 / 43 |
| serious Total, serious adverse events | 1 / 19 | 6 / 43 |
Outcome results
Primary
Part A/B: Observed Plasma Concentration of IVA and Their Metabolites (M1-IVA and M6-IVA)
Time frame: Day 4 (pre-dose, 2-4 hours, 6-8 hours post-dose); Day 15 (pre-dose); Week 4 (pre-dose); Week 8 (pre-dose, 2-4 hours, 6-8 hours post-dose); Week 12 (pre-dose); Week 18 (pre-dose) and Week 24 (pre-dose)
Population: PK set included participants who received at least 1 dose of study drug in Part A/B. Here the Number Analyzed signifies those participants who were evaluable for the specified time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: 3 to < 24 Months | Part A/B: Observed Plasma Concentration of IVA and Their Metabolites (M1-IVA and M6-IVA) | Day 4 (pre dose): IVA | 348 ng/ml | Standard Deviation 151 |
| Part A: 3 to < 24 Months | Part A/B: Observed Plasma Concentration of IVA and Their Metabolites (M1-IVA and M6-IVA) | Day 4 (pre dose): M1-IVA | 867 ng/ml | Standard Deviation 412 |
| Part A: 3 to < 24 Months | Part A/B: Observed Plasma Concentration of IVA and Their Metabolites (M1-IVA and M6-IVA) | Day 4 (pre dose): M6-IVA | 1570 ng/ml | Standard Deviation 570 |
| Part A: 3 to < 24 Months | Part A/B: Observed Plasma Concentration of IVA and Their Metabolites (M1-IVA and M6-IVA) | Day 4 (2-4 hrs post dose): IVA | 381 ng/ml | Standard Deviation 135 |
| Part A: 3 to < 24 Months | Part A/B: Observed Plasma Concentration of IVA and Their Metabolites (M1-IVA and M6-IVA) | Day 4 (2-4 hrs post dose): M1-IVA | 851 ng/ml | Standard Deviation 333 |
| Part A: 3 to < 24 Months | Part A/B: Observed Plasma Concentration of IVA and Their Metabolites (M1-IVA and M6-IVA) | Day 4 (2-4 hrs post dose): M6-IVA | 1370 ng/ml | Standard Deviation 450 |
| Part A: 3 to < 24 Months | Part A/B: Observed Plasma Concentration of IVA and Their Metabolites (M1-IVA and M6-IVA) | Day 4 (6-8 hrs post dose): IVA | 501 ng/ml | Standard Deviation 196 |
| Part A: 3 to < 24 Months | Part A/B: Observed Plasma Concentration of IVA and Their Metabolites (M1-IVA and M6-IVA) | Day 4 (6-8 hrs post dose): M1-IVA | 1190 ng/ml | Standard Deviation 420 |
| Part A: 3 to < 24 Months | Part A/B: Observed Plasma Concentration of IVA and Their Metabolites (M1-IVA and M6-IVA) | Day 4 (6-8 hrs post dose): M6-IVA | 1670 ng/ml | Standard Deviation 551 |
| Part A: 3 to < 24 Months | Part A/B: Observed Plasma Concentration of IVA and Their Metabolites (M1-IVA and M6-IVA) | Day 15 (pre dose): IVA | 191 ng/ml | Standard Deviation 134 |
| Part A: 3 to < 24 Months | Part A/B: Observed Plasma Concentration of IVA and Their Metabolites (M1-IVA and M6-IVA) | Day 15 (pre dose): M1-IVA | 614 ng/ml | Standard Deviation 378 |
| Part A: 3 to < 24 Months | Part A/B: Observed Plasma Concentration of IVA and Their Metabolites (M1-IVA and M6-IVA) | Day 15 (pre dose): M6-IVA | 1510 ng/ml | Standard Deviation 1110 |
| Part A: 3 to < 24 Months | Part A/B: Observed Plasma Concentration of IVA and Their Metabolites (M1-IVA and M6-IVA) | Week 4 (pre dose): IVA | 316 ng/ml | Standard Deviation 130 |
| Part A: 3 to < 24 Months | Part A/B: Observed Plasma Concentration of IVA and Their Metabolites (M1-IVA and M6-IVA) | Week 4 (pre dose): M1-IVA | 1170 ng/ml | Standard Deviation 577 |
| Part A: 3 to < 24 Months | Part A/B: Observed Plasma Concentration of IVA and Their Metabolites (M1-IVA and M6-IVA) | Week 4 (pre dose): M6-IVA | 3370 ng/ml | Standard Deviation 2330 |
| Part A: 3 to < 24 Months | Part A/B: Observed Plasma Concentration of IVA and Their Metabolites (M1-IVA and M6-IVA) | Week 8 (pre dose): IVA | 449 ng/ml | Standard Deviation 352 |
| Part A: 3 to < 24 Months | Part A/B: Observed Plasma Concentration of IVA and Their Metabolites (M1-IVA and M6-IVA) | Week 8 (pre dose): M1-IVA | 1030 ng/ml | Standard Deviation 476 |
| Part A: 3 to < 24 Months | Part A/B: Observed Plasma Concentration of IVA and Their Metabolites (M1-IVA and M6-IVA) | Week 8 (pre dose): M6-IVA | 2380 ng/ml | Standard Deviation 1500 |
| Part A: 3 to < 24 Months | Part A/B: Observed Plasma Concentration of IVA and Their Metabolites (M1-IVA and M6-IVA) | Week 8 (2-4 hrs post dose): IVA | 523 ng/ml | Standard Deviation 262 |
| Part A: 3 to < 24 Months | Part A/B: Observed Plasma Concentration of IVA and Their Metabolites (M1-IVA and M6-IVA) | Week 8 (2-4 hrs post dose): M1-IVA | 1360 ng/ml | Standard Deviation 982 |
| Part A: 3 to < 24 Months | Part A/B: Observed Plasma Concentration of IVA and Their Metabolites (M1-IVA and M6-IVA) | Week 8 (2-4 hrs post dose): M6-IVA | 2100 ng/ml | Standard Deviation 1540 |
| Part A: 3 to < 24 Months | Part A/B: Observed Plasma Concentration of IVA and Their Metabolites (M1-IVA and M6-IVA) | Week 8 (6-8 hrs post dose): IVA | 438 ng/ml | Standard Deviation 79.8 |
| Part A: 3 to < 24 Months | Part A/B: Observed Plasma Concentration of IVA and Their Metabolites (M1-IVA and M6-IVA) | Week 8 (6-8 hrs post dose): M1-IVA | 1420 ng/ml | Standard Deviation 606 |
| Part A: 3 to < 24 Months | Part A/B: Observed Plasma Concentration of IVA and Their Metabolites (M1-IVA and M6-IVA) | Week 8 (6-8 hrs post dose): M6-IVA | 2320 ng/ml | Standard Deviation 1330 |
| Part A: 3 to < 24 Months | Part A/B: Observed Plasma Concentration of IVA and Their Metabolites (M1-IVA and M6-IVA) | Week 12 (pre dose): IVA | 213 ng/ml | Standard Deviation 173 |
| Part A: 3 to < 24 Months | Part A/B: Observed Plasma Concentration of IVA and Their Metabolites (M1-IVA and M6-IVA) | Week 12 (pre dose): M1-IVA | 906 ng/ml | Standard Deviation 660 |
| Part A: 3 to < 24 Months | Part A/B: Observed Plasma Concentration of IVA and Their Metabolites (M1-IVA and M6-IVA) | Week 12 (pre dose): M6-IVA | 2500 ng/ml | Standard Deviation 1760 |
| Part A: 3 to < 24 Months | Part A/B: Observed Plasma Concentration of IVA and Their Metabolites (M1-IVA and M6-IVA) | Week 18 (pre dose): IVA | 226 ng/ml | Standard Deviation 153 |
| Part A: 3 to < 24 Months | Part A/B: Observed Plasma Concentration of IVA and Their Metabolites (M1-IVA and M6-IVA) | Week 18 (pre dose): M1-IVA | 815 ng/ml | Standard Deviation 470 |
| Part A: 3 to < 24 Months | Part A/B: Observed Plasma Concentration of IVA and Their Metabolites (M1-IVA and M6-IVA) | Week 18 (pre dose): M6-IVA | 2060 ng/ml | Standard Deviation 1190 |
| Part A: 3 to < 24 Months | Part A/B: Observed Plasma Concentration of IVA and Their Metabolites (M1-IVA and M6-IVA) | Week 24 (pre dose): IVA | 276 ng/ml | Standard Deviation 137 |
| Part A: 3 to < 24 Months | Part A/B: Observed Plasma Concentration of IVA and Their Metabolites (M1-IVA and M6-IVA) | Week 24 (pre dose): M1-IVA | 1120 ng/ml | Standard Deviation 496 |
| Part A: 3 to < 24 Months | Part A/B: Observed Plasma Concentration of IVA and Their Metabolites (M1-IVA and M6-IVA) | Week 24 (pre dose): M6-IVA | 2380 ng/ml | Standard Deviation 799 |
Primary
Part A: Observed Plasma Concentration of IVA and Their Metabolites (M1-IVA and M6-IVA)
Time frame: Pre-dose, 2-4 hours, 6-8 hours, 24-60 hours post-dose
Population: Pharmacokinetic (PK) set included participants who received at least 1 dose of study drug in Part A. Here the Number Analyzed signifies those participants who were evaluable for the specified time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: 3 to < 24 Months | Part A: Observed Plasma Concentration of IVA and Their Metabolites (M1-IVA and M6-IVA) | Pre dose: IVA | 654 nanogram per milliliter (ng/ml) | Standard Deviation 531 |
| Part A: 3 to < 24 Months | Part A: Observed Plasma Concentration of IVA and Their Metabolites (M1-IVA and M6-IVA) | Pre dose: M1-IVA | 1880 nanogram per milliliter (ng/ml) | Standard Deviation 1160 |
| Part A: 3 to < 24 Months | Part A: Observed Plasma Concentration of IVA and Their Metabolites (M1-IVA and M6-IVA) | Pre dose: M6-IVA | 2680 nanogram per milliliter (ng/ml) | Standard Deviation 1990 |
| Part A: 3 to < 24 Months | Part A: Observed Plasma Concentration of IVA and Their Metabolites (M1-IVA and M6-IVA) | 2-4 hrs post dose: IVA | 956 nanogram per milliliter (ng/ml) | Standard Deviation 497 |
| Part A: 3 to < 24 Months | Part A: Observed Plasma Concentration of IVA and Their Metabolites (M1-IVA and M6-IVA) | 2-4 hrs post dose: M1-IVA | 1990 nanogram per milliliter (ng/ml) | Standard Deviation 1160 |
| Part A: 3 to < 24 Months | Part A: Observed Plasma Concentration of IVA and Their Metabolites (M1-IVA and M6-IVA) | 2-4 hrs post dose: M6-IVA | 2460 nanogram per milliliter (ng/ml) | Standard Deviation 2110 |
| Part A: 3 to < 24 Months | Part A: Observed Plasma Concentration of IVA and Their Metabolites (M1-IVA and M6-IVA) | 6-8 hrs post dose: IVA | 1040 nanogram per milliliter (ng/ml) | Standard Deviation 623 |
| Part A: 3 to < 24 Months | Part A: Observed Plasma Concentration of IVA and Their Metabolites (M1-IVA and M6-IVA) | 6-8 hrs post dose: M1-IVA | 2440 nanogram per milliliter (ng/ml) | Standard Deviation 1260 |
| Part A: 3 to < 24 Months | Part A: Observed Plasma Concentration of IVA and Their Metabolites (M1-IVA and M6-IVA) | 6-8 hrs post dose: M6-IVA | 2880 nanogram per milliliter (ng/ml) | Standard Deviation 2180 |
| Part A: 3 to < 24 Months | Part A: Observed Plasma Concentration of IVA and Their Metabolites (M1-IVA and M6-IVA) | 24-60 hrs post dose: IVA | 129 nanogram per milliliter (ng/ml) | Standard Deviation 68.8 |
| Part A: 3 to < 24 Months | Part A: Observed Plasma Concentration of IVA and Their Metabolites (M1-IVA and M6-IVA) | 24-60 hrs post dose: M1-IVA | 508 nanogram per milliliter (ng/ml) | Standard Deviation 228 |
| Part A: 3 to < 24 Months | Part A: Observed Plasma Concentration of IVA and Their Metabolites (M1-IVA and M6-IVA) | 24-60 hrs post dose: M6-IVA | 1100 nanogram per milliliter (ng/ml) | Standard Deviation 982 |
Primary
Part A: Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious (TEAEs)
Time frame: Day 1 through Day 70
Population: Safety set included all participants who received at least 1 dose of study drug in Part A. This outcome measure was planned only for Part A: 3 to \<24 months arm.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part A: 3 to < 24 Months | Part A: Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious (TEAEs) | Participants with TEAEs | 10 Participants |
| Part A: 3 to < 24 Months | Part A: Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious (TEAEs) | Participants with Serious TEAEs | 1 Participants |
Primary
Part B +A/B: Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious (TEAEs)
Time frame: Day 1 through Week 38
Population: Safety Set included all participants who received at least 1 dose of study drug. The safety and tolerability analyses were assessed for the overall treatment arm. Therefore, the analysis is reported in a overall Part B+ A/B: 1 to \<24 months arm.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part A: 3 to < 24 Months | Part B +A/B: Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious (TEAEs) | Participants with TEAEs | 38 Participants |
| Part A: 3 to < 24 Months | Part B +A/B: Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious (TEAEs) | Participants with Serious (TEAEs) | 6 Participants |
Secondary
Part B + A/B: Absolute Change From Baseline in Sweat Chloride
Sweat samples were collected using an approved collection device.
Time frame: From Baseline at Week 24
Population: The Full Analysis Set (FAS) included all enrolled participants who were exposed to any amount of study drug in Part B + A/B. Here, Overall Number of Participants Analyzed signifies participants who were evaluable for this outcome.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A: 3 to < 24 Months | Part B + A/B: Absolute Change From Baseline in Sweat Chloride | -62.0 millimole per liter (mmol/L) | Standard Deviation 22.2 |
Secondary
Part B: Observed Plasma Concentration of IVA and Their Metabolites (M1-IVA and M6-IVA)
Time frame: Week 2 (pre-dose, 2-4 hours, 6-8 hours post-dose); Week 8 (pre-dose,1 hour, 4-hour post-dose); Week 24 (pre-dose, 2-4 hours post dose)
Population: PK set included participants who received at least 1 dose of study drug in Part B. Here the Number Analyzed signifies those participants who were evaluable for the specified time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: 3 to < 24 Months | Part B: Observed Plasma Concentration of IVA and Their Metabolites (M1-IVA and M6-IVA) | Week 2 (pre dose): IVA | 457 ng/ml | Standard Deviation 441 |
| Part A: 3 to < 24 Months | Part B: Observed Plasma Concentration of IVA and Their Metabolites (M1-IVA and M6-IVA) | Week 2 (pre dose): M1-IVA | 1340 ng/ml | Standard Deviation 934 |
| Part A: 3 to < 24 Months | Part B: Observed Plasma Concentration of IVA and Their Metabolites (M1-IVA and M6-IVA) | Week 2 (pre dose): M6-IVA | 1980 ng/ml | Standard Deviation 1790 |
| Part A: 3 to < 24 Months | Part B: Observed Plasma Concentration of IVA and Their Metabolites (M1-IVA and M6-IVA) | Week 2 (2-4 hrs post dose): IVA | 812 ng/ml | Standard Deviation 726 |
| Part A: 3 to < 24 Months | Part B: Observed Plasma Concentration of IVA and Their Metabolites (M1-IVA and M6-IVA) | Week 2 (2-4 hrs post dose): M1-IVA | 1560 ng/ml | Standard Deviation 1190 |
| Part A: 3 to < 24 Months | Part B: Observed Plasma Concentration of IVA and Their Metabolites (M1-IVA and M6-IVA) | Week 2 (2-4 hrs post dose): M6-IVA | 1770 ng/ml | Standard Deviation 1970 |
| Part A: 3 to < 24 Months | Part B: Observed Plasma Concentration of IVA and Their Metabolites (M1-IVA and M6-IVA) | Week 2 (6-8 hrs post dose): IVA | 969 ng/ml | Standard Deviation 705 |
| Part A: 3 to < 24 Months | Part B: Observed Plasma Concentration of IVA and Their Metabolites (M1-IVA and M6-IVA) | Week 2 (6-8 hrs post dose): M1-IVA | 2210 ng/ml | Standard Deviation 1360 |
| Part A: 3 to < 24 Months | Part B: Observed Plasma Concentration of IVA and Their Metabolites (M1-IVA and M6-IVA) | Week 2 (6-8 hrs post dose): M6-IVA | 2140 ng/ml | Standard Deviation 1880 |
| Part A: 3 to < 24 Months | Part B: Observed Plasma Concentration of IVA and Their Metabolites (M1-IVA and M6-IVA) | Week 8 (pre dose): IVA | 404 ng/ml | Standard Deviation 376 |
| Part A: 3 to < 24 Months | Part B: Observed Plasma Concentration of IVA and Their Metabolites (M1-IVA and M6-IVA) | Week 8 (pre dose): M1-IVA | 1220 ng/ml | Standard Deviation 782 |
| Part A: 3 to < 24 Months | Part B: Observed Plasma Concentration of IVA and Their Metabolites (M1-IVA and M6-IVA) | Week 8 (pre dose): M6-IVA | 1720 ng/ml | Standard Deviation 1110 |
| Part A: 3 to < 24 Months | Part B: Observed Plasma Concentration of IVA and Their Metabolites (M1-IVA and M6-IVA) | Week 8 (1 hrs post dose): IVA | 466 ng/ml | Standard Deviation 384 |
| Part A: 3 to < 24 Months | Part B: Observed Plasma Concentration of IVA and Their Metabolites (M1-IVA and M6-IVA) | Week 8 (1 hrs post dose): M1-IVA | 1100 ng/ml | Standard Deviation 670 |
| Part A: 3 to < 24 Months | Part B: Observed Plasma Concentration of IVA and Their Metabolites (M1-IVA and M6-IVA) | Week 8 (1 hrs post dose): M6-IVA | 1500 ng/ml | Standard Deviation 881 |
| Part A: 3 to < 24 Months | Part B: Observed Plasma Concentration of IVA and Their Metabolites (M1-IVA and M6-IVA) | Week 8 (4 hrs post dose): IVA | 996 ng/ml | Standard Deviation 520 |
| Part A: 3 to < 24 Months | Part B: Observed Plasma Concentration of IVA and Their Metabolites (M1-IVA and M6-IVA) | Week 8 (4 hrs post dose): M1-IVA | 2130 ng/ml | Standard Deviation 950 |
| Part A: 3 to < 24 Months | Part B: Observed Plasma Concentration of IVA and Their Metabolites (M1-IVA and M6-IVA) | Week 8 (4 hrs post dose): M6-IVA | 1750 ng/ml | Standard Deviation 1010 |
| Part A: 3 to < 24 Months | Part B: Observed Plasma Concentration of IVA and Their Metabolites (M1-IVA and M6-IVA) | Week 24 (pre dose): IVA | 301 ng/ml | Standard Deviation 204 |
| Part A: 3 to < 24 Months | Part B: Observed Plasma Concentration of IVA and Their Metabolites (M1-IVA and M6-IVA) | Week 24 (pre dose): M1-IVA | 1050 ng/ml | Standard Deviation 492 |
| Part A: 3 to < 24 Months | Part B: Observed Plasma Concentration of IVA and Their Metabolites (M1-IVA and M6-IVA) | Week 24 (pre dose): M6-IVA | 1600 ng/ml | Standard Deviation 783 |
| Part A: 3 to < 24 Months | Part B: Observed Plasma Concentration of IVA and Their Metabolites (M1-IVA and M6-IVA) | Week 24 (2-4 hrs post dose): IVA | 794 ng/ml | Standard Deviation 480 |
| Part A: 3 to < 24 Months | Part B: Observed Plasma Concentration of IVA and Their Metabolites (M1-IVA and M6-IVA) | Week 24 (2-4 hrs post dose): M1-IVA | 1540 ng/ml | Standard Deviation 783 |
| Part A: 3 to < 24 Months | Part B: Observed Plasma Concentration of IVA and Their Metabolites (M1-IVA and M6-IVA) | Week 24 (2-4 hrs post dose): M6-IVA | 1320 ng/ml | Standard Deviation 592 |