Herpes Simplex
Conditions
Keywords
Infants, Herpes simplex infection
Brief summary
This study will evaluate the acceptability and safety of famciclovir in infants with herpes simplex infection
Interventions
DRUGfamciclovir
Administered orally as a single individualized dose between 25-200 mg based on body weight.
Sponsors
Novartis
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
1 Months to 1 Years
Healthy volunteers
No
Inclusion criteria
* Male and female patients from 1 month up to 1 year of age with herpes simplex infection
Exclusion criteria
* Patients with gestational age less than 32 weeks. Patients unable to swallow. Patients with history of malabsorption or previous gastrointestinal surgery. Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics of Single Dose - Tmax | Plasma samples were collected at 0.5, 1, 4 and 6 hours after dosing. | Measured by Tmax - The time after administration of a drug when the maximum plasma concentration is reached. |
| Pharmacokinetics of Single Dose - Cmax | Plasma samples were collected at 0.5, 1, 4 and 6 hours after dosing. | Measured by Cmax - The maximum plasma concentration of study medication |
| Pharmacokinetics of Single Dose - AUC(0-tlast) | Plasma samples were collected at 0.5, 1, 4 and 6 hours after dosing. | Measured by AUC(0-tlast) - Area under the plasma concentration time curve from time zero to the last quantifiable concentration-timepoint. |
| Pharmacokinetics of Single Dose - AUC(0-6h) | Plasma samples were collected at 0.5, 1, 4 and 6 hours after dosing. | Measured by AUC(0-6h) - Area under the plasma concentration time curve from time zero up to 6 hours post dose (i.e. the time of the last sample). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Safety Assessed by AEs, SAEs | 38 days | AEs and SAEs were collected during patient's stay in the clinic for PK sampling up to Hour 8, then at day 2 visit, 8 days(safety follow-up call) and 38 days (safety follow-up call) post dose. |
| Acceptability of the Famciclovir Pediatric Formulation as Assessed by Study Personnel | Immediately after dosing | Assessed by the study personnel using a 5-point scale after dosing: 1. Very badly accepted/unacceptable: infant showed great displeasure, compromising use of formulation 2. Badly but accepted: infant showed displeasure with dosing but could be coaxed to take complete dose 3. Neither good nor bad: infant showed no apparent displeasure and with little effort was coaxed to take complete dose 4. Well accepted: infant appeared to enjoy the formulation and with little coaxing ingested most of dose 5. Very well accepted: infant appeared eager and ingested most of dose without special coaxing |
| Safety Assessed by Labs | 2 days | Samples for safety labs were obtained at baseline and Day 2 visit and samples were analyzed by local accredited laboratory. |
| Tolerability of of the Famciclovir Pediatric Formulation as Assessed by Study Personnel. | 30 minutes after dosing | Tolerability was assessed by the study personnel 30 minutes after dosing using the following scale: 1. Significant emesis occurred, 2. Infant spit out most of the dose ingesting less than half of what was administered, 3. Infant spit out some of the dose, but ingested at least 50% of what was administered, 4. Infant was able to ingest and retain the dose administered |
| Acceptability of the Famciclovir Pediatric Formulation as Assessed by the Patient's Caregiver | Immediately after dosing | Assessed by the caregiver using a 5-point scale immediately after dosing: 1. Very badly accepted/unacceptable: infant showed great displeasure, compromising use of formulation 2. Badly but accepted: infant showed displeasure with dosing but could be coaxed to take complete dose 3. Neither good nor bad: infant showed no apparent displeasure and with little effort was coaxed to take complete dose 4. Well accepted: infant appeared to enjoy the formulation and with little coaxing ingested most of dose 5. Very well accepted: infant appeared eager and ingested most of dose without special coaxing |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Famciclovir Famciclovir was administered orally as a suspension in OraSweet® on Day 1. Patients received a single, individualized dose between 25-200 mg based on body weight. | 18 |
| Total | 18 |
Baseline characteristics
| Characteristic | Famciclovir |
|---|---|
| Age Continuous | 4 months STANDARD_DEVIATION 3.6 |
| Age, Customized 1 to <3 months | 8 participants |
| Age, Customized 3 to <6 months | 5 participants |
| Age, Customized 6 to 12 months | 5 participants |
| Sex: Female, Male Female | 7 Participants |
| Sex: Female, Male Male | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 8 / 18 |
| serious Total, serious adverse events | 1 / 18 |
Outcome results
Primary
Pharmacokinetics of Single Dose - AUC(0-6h)
Measured by AUC(0-6h) - Area under the plasma concentration time curve from time zero up to 6 hours post dose (i.e. the time of the last sample).
Time frame: Plasma samples were collected at 0.5, 1, 4 and 6 hours after dosing.
Population: Analysis population included the intent-to-treat population, with the exception of one patient in the 1 to \<3 months age group who did not have PK samples taken due to emesis reported after study medication administration.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Famciclovir: Infants 1 to <3 Months | Pharmacokinetics of Single Dose - AUC(0-6h) | 2.22 (μg/mL)•h | Standard Deviation 1.23 |
| Famciclovir: Infants 3 to <6 Months | Pharmacokinetics of Single Dose - AUC(0-6h) | 3.16 (μg/mL)•h | Standard Deviation 0.68 |
| Famciclovir: Infants 6 to 12 Months | Pharmacokinetics of Single Dose - AUC(0-6h) | 8.77 (μg/mL)•h | Standard Deviation 2.14 |
Primary
Pharmacokinetics of Single Dose - AUC(0-tlast)
Measured by AUC(0-tlast) - Area under the plasma concentration time curve from time zero to the last quantifiable concentration-timepoint.
Time frame: Plasma samples were collected at 0.5, 1, 4 and 6 hours after dosing.
Population: Analysis population included the intent-to-treat population, with the exception of one patient in the 1 to \<3 months age group who did not have PK samples taken due to emesis reported after study medication administration.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Famciclovir: Infants 1 to <3 Months | Pharmacokinetics of Single Dose - AUC(0-tlast) | 2.09 (μg/mL)•h | Standard Deviation 1.38 |
| Famciclovir: Infants 3 to <6 Months | Pharmacokinetics of Single Dose - AUC(0-tlast) | 3.16 (μg/mL)•h | Standard Deviation 0.68 |
| Famciclovir: Infants 6 to 12 Months | Pharmacokinetics of Single Dose - AUC(0-tlast) | 8.68 (μg/mL)•h | Standard Deviation 2.09 |
Primary
Pharmacokinetics of Single Dose - Cmax
Measured by Cmax - The maximum plasma concentration of study medication
Time frame: Plasma samples were collected at 0.5, 1, 4 and 6 hours after dosing.
Population: Analysis population included the intent-to-treat population, with the exception of one patient in the 1 to \<3 months age group who did not have PK samples taken due to emesis reported after study medication administration.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Famciclovir: Infants 1 to <3 Months | Pharmacokinetics of Single Dose - Cmax | 0.69 μg/mL | Standard Deviation 0.41 |
| Famciclovir: Infants 3 to <6 Months | Pharmacokinetics of Single Dose - Cmax | 0.74 μg/mL | Standard Deviation 0.17 |
| Famciclovir: Infants 6 to 12 Months | Pharmacokinetics of Single Dose - Cmax | 3.24 μg/mL | Standard Deviation 1.01 |
Primary
Pharmacokinetics of Single Dose - Tmax
Measured by Tmax - The time after administration of a drug when the maximum plasma concentration is reached.
Time frame: Plasma samples were collected at 0.5, 1, 4 and 6 hours after dosing.
Population: Analysis population included the intent-to-treat population, with the exception of one patient in the 1 to \<3 months age group who did not have PK samples taken due to emesis reported after study medication administration.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Famciclovir: Infants 1 to <3 Months | Pharmacokinetics of Single Dose - Tmax | 1.00 hours |
| Famciclovir: Infants 3 to <6 Months | Pharmacokinetics of Single Dose - Tmax | 4 hours |
| Famciclovir: Infants 6 to 12 Months | Pharmacokinetics of Single Dose - Tmax | 1.02 hours |
Secondary
Acceptability of the Famciclovir Pediatric Formulation as Assessed by Study Personnel
Assessed by the study personnel using a 5-point scale after dosing: 1. Very badly accepted/unacceptable: infant showed great displeasure, compromising use of formulation 2. Badly but accepted: infant showed displeasure with dosing but could be coaxed to take complete dose 3. Neither good nor bad: infant showed no apparent displeasure and with little effort was coaxed to take complete dose 4. Well accepted: infant appeared to enjoy the formulation and with little coaxing ingested most of dose 5. Very well accepted: infant appeared eager and ingested most of dose without special coaxing
Time frame: Immediately after dosing
Population: Safety population.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Famciclovir: Infants 1 to <3 Months | Acceptability of the Famciclovir Pediatric Formulation as Assessed by Study Personnel | Well accepted | 2 Participants |
| Famciclovir: Infants 1 to <3 Months | Acceptability of the Famciclovir Pediatric Formulation as Assessed by Study Personnel | Badly but accepted | 0 Participants |
| Famciclovir: Infants 1 to <3 Months | Acceptability of the Famciclovir Pediatric Formulation as Assessed by Study Personnel | Very well accepted | 4 Participants |
| Famciclovir: Infants 1 to <3 Months | Acceptability of the Famciclovir Pediatric Formulation as Assessed by Study Personnel | Neither good nor bad | 0 Participants |
| Famciclovir: Infants 1 to <3 Months | Acceptability of the Famciclovir Pediatric Formulation as Assessed by Study Personnel | Very badly / unacceptable | 1 Participants |
| Famciclovir: Infants 3 to <6 Months | Acceptability of the Famciclovir Pediatric Formulation as Assessed by Study Personnel | Neither good nor bad | 2 Participants |
| Famciclovir: Infants 3 to <6 Months | Acceptability of the Famciclovir Pediatric Formulation as Assessed by Study Personnel | Well accepted | 0 Participants |
| Famciclovir: Infants 3 to <6 Months | Acceptability of the Famciclovir Pediatric Formulation as Assessed by Study Personnel | Very well accepted | 3 Participants |
| Famciclovir: Infants 3 to <6 Months | Acceptability of the Famciclovir Pediatric Formulation as Assessed by Study Personnel | Badly but accepted | 0 Participants |
| Famciclovir: Infants 3 to <6 Months | Acceptability of the Famciclovir Pediatric Formulation as Assessed by Study Personnel | Very badly / unacceptable | 0 Participants |
| Famciclovir: Infants 6 to 12 Months | Acceptability of the Famciclovir Pediatric Formulation as Assessed by Study Personnel | Neither good nor bad | 2 Participants |
| Famciclovir: Infants 6 to 12 Months | Acceptability of the Famciclovir Pediatric Formulation as Assessed by Study Personnel | Very badly / unacceptable | 0 Participants |
| Famciclovir: Infants 6 to 12 Months | Acceptability of the Famciclovir Pediatric Formulation as Assessed by Study Personnel | Badly but accepted | 1 Participants |
| Famciclovir: Infants 6 to 12 Months | Acceptability of the Famciclovir Pediatric Formulation as Assessed by Study Personnel | Well accepted | 1 Participants |
| Famciclovir: Infants 6 to 12 Months | Acceptability of the Famciclovir Pediatric Formulation as Assessed by Study Personnel | Very well accepted | 1 Participants |
| Total | Acceptability of the Famciclovir Pediatric Formulation as Assessed by Study Personnel | Well accepted | 3 Participants |
| Total | Acceptability of the Famciclovir Pediatric Formulation as Assessed by Study Personnel | Badly but accepted | 1 Participants |
| Total | Acceptability of the Famciclovir Pediatric Formulation as Assessed by Study Personnel | Very badly / unacceptable | 1 Participants |
| Total | Acceptability of the Famciclovir Pediatric Formulation as Assessed by Study Personnel | Neither good nor bad | 4 Participants |
| Total | Acceptability of the Famciclovir Pediatric Formulation as Assessed by Study Personnel | Very well accepted | 8 Participants |
Secondary
Acceptability of the Famciclovir Pediatric Formulation as Assessed by the Patient's Caregiver
Assessed by the caregiver using a 5-point scale immediately after dosing: 1. Very badly accepted/unacceptable: infant showed great displeasure, compromising use of formulation 2. Badly but accepted: infant showed displeasure with dosing but could be coaxed to take complete dose 3. Neither good nor bad: infant showed no apparent displeasure and with little effort was coaxed to take complete dose 4. Well accepted: infant appeared to enjoy the formulation and with little coaxing ingested most of dose 5. Very well accepted: infant appeared eager and ingested most of dose without special coaxing
Time frame: Immediately after dosing
Population: Safety population.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Famciclovir: Infants 1 to <3 Months | Acceptability of the Famciclovir Pediatric Formulation as Assessed by the Patient's Caregiver | Well accepted | 2 Participants |
| Famciclovir: Infants 1 to <3 Months | Acceptability of the Famciclovir Pediatric Formulation as Assessed by the Patient's Caregiver | Badly but accepted | 0 Participants |
| Famciclovir: Infants 1 to <3 Months | Acceptability of the Famciclovir Pediatric Formulation as Assessed by the Patient's Caregiver | Very well accepted | 4 Participants |
| Famciclovir: Infants 1 to <3 Months | Acceptability of the Famciclovir Pediatric Formulation as Assessed by the Patient's Caregiver | Neither good nor bad | 0 Participants |
| Famciclovir: Infants 1 to <3 Months | Acceptability of the Famciclovir Pediatric Formulation as Assessed by the Patient's Caregiver | Very badly / unacceptable | 1 Participants |
| Famciclovir: Infants 3 to <6 Months | Acceptability of the Famciclovir Pediatric Formulation as Assessed by the Patient's Caregiver | Neither good nor bad | 2 Participants |
| Famciclovir: Infants 3 to <6 Months | Acceptability of the Famciclovir Pediatric Formulation as Assessed by the Patient's Caregiver | Well accepted | 0 Participants |
| Famciclovir: Infants 3 to <6 Months | Acceptability of the Famciclovir Pediatric Formulation as Assessed by the Patient's Caregiver | Very well accepted | 3 Participants |
| Famciclovir: Infants 3 to <6 Months | Acceptability of the Famciclovir Pediatric Formulation as Assessed by the Patient's Caregiver | Badly but accepted | 0 Participants |
| Famciclovir: Infants 3 to <6 Months | Acceptability of the Famciclovir Pediatric Formulation as Assessed by the Patient's Caregiver | Very badly / unacceptable | 0 Participants |
| Famciclovir: Infants 6 to 12 Months | Acceptability of the Famciclovir Pediatric Formulation as Assessed by the Patient's Caregiver | Neither good nor bad | 1 Participants |
| Famciclovir: Infants 6 to 12 Months | Acceptability of the Famciclovir Pediatric Formulation as Assessed by the Patient's Caregiver | Very badly / unacceptable | 0 Participants |
| Famciclovir: Infants 6 to 12 Months | Acceptability of the Famciclovir Pediatric Formulation as Assessed by the Patient's Caregiver | Badly but accepted | 1 Participants |
| Famciclovir: Infants 6 to 12 Months | Acceptability of the Famciclovir Pediatric Formulation as Assessed by the Patient's Caregiver | Well accepted | 2 Participants |
| Famciclovir: Infants 6 to 12 Months | Acceptability of the Famciclovir Pediatric Formulation as Assessed by the Patient's Caregiver | Very well accepted | 1 Participants |
| Total | Acceptability of the Famciclovir Pediatric Formulation as Assessed by the Patient's Caregiver | Well accepted | 4 Participants |
| Total | Acceptability of the Famciclovir Pediatric Formulation as Assessed by the Patient's Caregiver | Badly but accepted | 1 Participants |
| Total | Acceptability of the Famciclovir Pediatric Formulation as Assessed by the Patient's Caregiver | Very badly / unacceptable | 1 Participants |
| Total | Acceptability of the Famciclovir Pediatric Formulation as Assessed by the Patient's Caregiver | Neither good nor bad | 3 Participants |
| Total | Acceptability of the Famciclovir Pediatric Formulation as Assessed by the Patient's Caregiver | Very well accepted | 8 Participants |
Secondary
Safety Assessed by AEs, SAEs
AEs and SAEs were collected during patient's stay in the clinic for PK sampling up to Hour 8, then at day 2 visit, 8 days(safety follow-up call) and 38 days (safety follow-up call) post dose.
Time frame: 38 days
Secondary
Safety Assessed by Labs
Samples for safety labs were obtained at baseline and Day 2 visit and samples were analyzed by local accredited laboratory.
Time frame: 2 days
Secondary
Tolerability of of the Famciclovir Pediatric Formulation as Assessed by Study Personnel.
Tolerability was assessed by the study personnel 30 minutes after dosing using the following scale: 1. Significant emesis occurred, 2. Infant spit out most of the dose ingesting less than half of what was administered, 3. Infant spit out some of the dose, but ingested at least 50% of what was administered, 4. Infant was able to ingest and retain the dose administered
Time frame: 30 minutes after dosing
Population: Safety population.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Famciclovir: Infants 1 to <3 Months | Tolerability of of the Famciclovir Pediatric Formulation as Assessed by Study Personnel. | Significant emesis occurred | 1 Participants |
| Famciclovir: Infants 1 to <3 Months | Tolerability of of the Famciclovir Pediatric Formulation as Assessed by Study Personnel. | Spit out most of the dose, ingested less than half | 0 Participants |
| Famciclovir: Infants 1 to <3 Months | Tolerability of of the Famciclovir Pediatric Formulation as Assessed by Study Personnel. | Spit out some of the dose, ingested at least 50% | 0 Participants |
| Famciclovir: Infants 1 to <3 Months | Tolerability of of the Famciclovir Pediatric Formulation as Assessed by Study Personnel. | Able to ingest and retain dose | 7 Participants |
| Famciclovir: Infants 3 to <6 Months | Tolerability of of the Famciclovir Pediatric Formulation as Assessed by Study Personnel. | Spit out most of the dose, ingested less than half | 0 Participants |
| Famciclovir: Infants 3 to <6 Months | Tolerability of of the Famciclovir Pediatric Formulation as Assessed by Study Personnel. | Spit out some of the dose, ingested at least 50% | 0 Participants |
| Famciclovir: Infants 3 to <6 Months | Tolerability of of the Famciclovir Pediatric Formulation as Assessed by Study Personnel. | Able to ingest and retain dose | 5 Participants |
| Famciclovir: Infants 3 to <6 Months | Tolerability of of the Famciclovir Pediatric Formulation as Assessed by Study Personnel. | Significant emesis occurred | 0 Participants |
| Famciclovir: Infants 6 to 12 Months | Tolerability of of the Famciclovir Pediatric Formulation as Assessed by Study Personnel. | Spit out some of the dose, ingested at least 50% | 0 Participants |
| Famciclovir: Infants 6 to 12 Months | Tolerability of of the Famciclovir Pediatric Formulation as Assessed by Study Personnel. | Spit out most of the dose, ingested less than half | 0 Participants |
| Famciclovir: Infants 6 to 12 Months | Tolerability of of the Famciclovir Pediatric Formulation as Assessed by Study Personnel. | Able to ingest and retain dose | 5 Participants |
| Famciclovir: Infants 6 to 12 Months | Tolerability of of the Famciclovir Pediatric Formulation as Assessed by Study Personnel. | Significant emesis occurred | 0 Participants |
| Total | Tolerability of of the Famciclovir Pediatric Formulation as Assessed by Study Personnel. | Able to ingest and retain dose | 17 Participants |
| Total | Tolerability of of the Famciclovir Pediatric Formulation as Assessed by Study Personnel. | Spit out most of the dose, ingested less than half | 0 Participants |
| Total | Tolerability of of the Famciclovir Pediatric Formulation as Assessed by Study Personnel. | Significant emesis occurred | 1 Participants |
| Total | Tolerability of of the Famciclovir Pediatric Formulation as Assessed by Study Personnel. | Spit out some of the dose, ingested at least 50% | 0 Participants |