Trial Outcomes & Findings for Safety and Pharmacokinetics of Famciclovir Single 1500 mg Dose in Adolescents With Recurrent Herpes Labialis (NCT NCT00878072)
NCT ID: NCT00878072
Last Updated: 2021-06-25
Results Overview
AEs are defined as any unfavorable and unintended diagnosis, symptom, sign (including an abnormal laboratory finding), syndrome or disease which either occurs during study, having been absent at baseline, or, if present at baseline, appears to worsen. Serious adverse events are any untoward medical occurrences that result in death, are life threatening, require (or prolong) hospitalization, cause persistent or significant disability/incapacity, result in congenital anomalies or birth defects, or are other conditions which in judgment of investigators represent significant hazards.
COMPLETED
PHASE2/PHASE3
53 participants
From Start of the Study up to Day 36
2021-06-25
Participant Flow
The study was conducted at 10 centers in United States.
Participant milestones
| Measure |
Famciclovir
Participants received single oral doses of three 500 milligrams (mg) Famciclovir tablets on Day 1.
|
|---|---|
|
Overall Study
STARTED
|
53
|
|
Overall Study
COMPLETED
|
51
|
|
Overall Study
NOT COMPLETED
|
2
|
Reasons for withdrawal
| Measure |
Famciclovir
Participants received single oral doses of three 500 milligrams (mg) Famciclovir tablets on Day 1.
|
|---|---|
|
Overall Study
Withdrew consent
|
2
|
Baseline Characteristics
Safety and Pharmacokinetics of Famciclovir Single 1500 mg Dose in Adolescents With Recurrent Herpes Labialis
Baseline characteristics by cohort
| Measure |
Famciclovir
n=53 Participants
Participants received single oral doses of three 500 milligrams (mg) Famciclovir tablets on Day 1.
|
|---|---|
|
Age, Continuous
|
14.4 years
STANDARD_DEVIATION 1.86 • n=5 Participants
|
|
Sex: Female, Male
Female
|
33 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
20 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: From Start of the Study up to Day 36Population: The analysis was performed on safety set population defined as all participants who received study drug and had at least one post-baseline safety assessment.
AEs are defined as any unfavorable and unintended diagnosis, symptom, sign (including an abnormal laboratory finding), syndrome or disease which either occurs during study, having been absent at baseline, or, if present at baseline, appears to worsen. Serious adverse events are any untoward medical occurrences that result in death, are life threatening, require (or prolong) hospitalization, cause persistent or significant disability/incapacity, result in congenital anomalies or birth defects, or are other conditions which in judgment of investigators represent significant hazards.
Outcome measures
| Measure |
Famciclovir (Participants Aged 12 to Less Than [<] 15 Years)
n=28 Participants
Participants aged 12 to \<15 years received single oral doses of three 500 milligrams (mg) Famciclovir tablets on Day 1.
|
Famciclovir (Participants Aged 15 to Less Than [<] 18 Years)
n=25 Participants
Participants aged 15 to \<18 years received single oral doses of three 500 milligrams (mg) Famciclovir tablets on Day 1.
|
|---|---|---|
|
Number of Participants Reported Adverse Events (AEs), Serious Adverse Events (SAEs)
Adverse Events
|
6 Participants
|
6 Participants
|
|
Number of Participants Reported Adverse Events (AEs), Serious Adverse Events (SAEs)
Serious Adverse Events
|
0 Participants
|
0 Participants
|
PRIMARY outcome
Timeframe: From Start of the Study up to Day 36Population: The analysis was performed on safety set population defined as all participants who received study drug and had at least one post-baseline safety assessment.
Participants with laboratory values outside the defined normal range were graded as clinically significant laboratory abnormalities. Laboratory values were assessed according to the National Cancer Institute- Common terminology criteria for Adverse Events (NCI-CTCAE). Hematology, Urinalysis and clinical chemistry were reported .
Outcome measures
| Measure |
Famciclovir (Participants Aged 12 to Less Than [<] 15 Years)
n=28 Participants
Participants aged 12 to \<15 years received single oral doses of three 500 milligrams (mg) Famciclovir tablets on Day 1.
|
Famciclovir (Participants Aged 15 to Less Than [<] 18 Years)
n=25 Participants
Participants aged 15 to \<18 years received single oral doses of three 500 milligrams (mg) Famciclovir tablets on Day 1.
|
|---|---|---|
|
Number of Participants With Clinically Significant Laboratory Abnormalities
Hematology
|
0 Participants
|
0 Participants
|
|
Number of Participants With Clinically Significant Laboratory Abnormalities
Clinical chemistry
|
0 Participants
|
0 Participants
|
|
Number of Participants With Clinically Significant Laboratory Abnormalities
Urinalysis
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6 and 10 hours Post-dosePopulation: The analysis was performed in PK (Pharmacokinetics) analysis set (PAS) population, defined as all participants who participated in the PK assessment part and who did not miss more than one PK blood sampling. Here, number of participants analyzed refer to the number of participants evaluable for this outcome at specified time point.
Tmax was defined as the time to reach maximum plasma concentration. Penciclovir (active metabolite from famciclovir) and 6-deoxypenciclovir (first intermediate metabolite from famciclovir) were determined by using a validated liquid chromatography/tandem mass spectrometry (LC/MS/MS) method. The limit of quantification was 0.15 microgram (µg)/milliliter (mL) for both compounds. Calculations were done in WinNonlin 5.0.1, using non-compartmental methods.
Outcome measures
| Measure |
Famciclovir (Participants Aged 12 to Less Than [<] 15 Years)
n=8 Participants
Participants aged 12 to \<15 years received single oral doses of three 500 milligrams (mg) Famciclovir tablets on Day 1.
|
Famciclovir (Participants Aged 15 to Less Than [<] 18 Years)
n=8 Participants
Participants aged 15 to \<18 years received single oral doses of three 500 milligrams (mg) Famciclovir tablets on Day 1.
|
|---|---|---|
|
Time of Maximum Observed Plasma Concentration (Tmax) of Penciclovir (Active Metabolite From Famciclovir) and 6-deoxypenciclovir (First Intermediate Metabolite From Famciclovir)
|
1 Hours
Interval 0.83 to 3.0
|
1 Hours
Interval 0.5 to 2.0
|
SECONDARY outcome
Timeframe: Pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6 and 10 hours Post-dosePopulation: The analysis was performed in PK (Pharmacokinetics) analysis set (PAS) population, defined as all participants who participated in the PK assessment part and who did not miss more than one PK blood sampling. Here, number of participants analyzed refer to the number of participants evaluable for this outcome at specified time point.
Cmax was defined as the maximum observed plasma concentration. Penciclovir (active metabolite from famciclovir) and 6-deoxypenciclovir (first intermediate metabolite from famciclovir) were determined by using LC/MS/MS method. The limit of quantification was 0.15 µg/mL for both compounds. Calculations were done in WinNonlin 5.0.1, using non-compartmental methods.
Outcome measures
| Measure |
Famciclovir (Participants Aged 12 to Less Than [<] 15 Years)
n=8 Participants
Participants aged 12 to \<15 years received single oral doses of three 500 milligrams (mg) Famciclovir tablets on Day 1.
|
Famciclovir (Participants Aged 15 to Less Than [<] 18 Years)
n=8 Participants
Participants aged 15 to \<18 years received single oral doses of three 500 milligrams (mg) Famciclovir tablets on Day 1.
|
|---|---|---|
|
Maximum Plasma Concentration (Cmax) of Penciclovir (Active Metabolite From Famciclovir) and 6-deoxypenciclovir (First Intermediate Metabolite From Famciclovir)
|
9.37 Microgram (µg)/milliliter(mL)
Standard Deviation 2.68
|
3.32 Microgram (µg)/milliliter(mL)
Standard Deviation 2.36
|
SECONDARY outcome
Timeframe: Pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6 and 10 hours Post-dosePopulation: The analysis was performed in PK (Pharmacokinetics) analysis set (PAS) population, defined as all participants who participated in the PK assessment part and who did not miss more than one PK blood sampling. Here, number of participants analyzed refer to the number of participants evaluable for this outcome at specified time point.
AUC 0-tlast was defined as the area under the plasma concentration-time curve from time zero up to the last quantifiable concentration (Clast) calculated by the linear trapezoidal rule. Penciclovir (active metabolite from famciclovir) and 6-deoxypenciclovir (first intermediate metabolite from famciclovir) were determined by using LC/MS/MS method. The limit of quantification was 0.15 µg/mL for both compounds. Calculations were done in WinNonlin 5.0.1, using non-compartmental methods.
Outcome measures
| Measure |
Famciclovir (Participants Aged 12 to Less Than [<] 15 Years)
n=8 Participants
Participants aged 12 to \<15 years received single oral doses of three 500 milligrams (mg) Famciclovir tablets on Day 1.
|
Famciclovir (Participants Aged 15 to Less Than [<] 18 Years)
n=8 Participants
Participants aged 15 to \<18 years received single oral doses of three 500 milligrams (mg) Famciclovir tablets on Day 1.
|
|---|---|---|
|
Area Under the Plasma Concentration of Penciclovir (Active Metabolite From Famciclovir) and 6-deoxypenciclovir (First Intermediate Metabolite From Famciclovir)
|
30.80 Microgram(µg)/Milliliter(mL)*Hour(h)
Standard Deviation 5.52
|
5.42 Microgram(µg)/Milliliter(mL)*Hour(h)
Standard Deviation 3.58
|
SECONDARY outcome
Timeframe: Pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6 and 10 hours Post-dosePopulation: The analysis was performed in PK (Pharmacokinetics) analysis set (PAS) population, defined as all participants who participated in the PK assessment part and who did not miss more than one PK blood sampling. Here, number of participants analyzed refer to the number of participants evaluable for this outcome at specified time point.
AUC 0-infinity was defined as the area under the plasma concentration time curve from time zero to infinity = AUC 0-tlast + C last /λ z, where λz is the apparent elimination rate constant estimated by linear regression analysis of the terminal portion of the log-linear plasma concentration-time curve. Penciclovir (active metabolite from famciclovir) and 6-deoxypenciclovir (first intermediate metabolite from famciclovir) were determined by using LC/MS/MS method. The limit of quantification was 0.15 µg/mL for both compounds. Calculations were done in WinNonlin 5.0.1, using non-compartmental methods.
Outcome measures
| Measure |
Famciclovir (Participants Aged 12 to Less Than [<] 15 Years)
n=8 Participants
Participants aged 12 to \<15 years received single oral doses of three 500 milligrams (mg) Famciclovir tablets on Day 1.
|
Famciclovir (Participants Aged 15 to Less Than [<] 18 Years)
n=6 Participants
Participants aged 15 to \<18 years received single oral doses of three 500 milligrams (mg) Famciclovir tablets on Day 1.
|
|---|---|---|
|
Area Under the Plasma Concentration-Time Curve From Time 0 to Infinity (AUC 0-infinity) of Penciclovir (Active Metabolite From Famciclovir) and 6-deoxypenciclovir (First Intermediate Metabolite From Famciclovir)
|
31.76 Microgram(µg)/Milliliter(mL)*Hour(h)
Standard Deviation 5.53
|
6.61 Microgram(µg)/Milliliter(mL)*Hour(h)
Standard Deviation 3.89
|
SECONDARY outcome
Timeframe: Pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6 and 10 hours Post-dosePopulation: The analysis was performed in PK (Pharmacokinetics) analysis set (PAS) population, defined as all participants who participated in the PK assessment part and who did not miss more than one PK blood sampling. Here, number of participants analyzed refer to the number of participants evaluable for this outcome at specified time point.
T½ was defined as the apparent terminal elimination half-life= ln 2/ λz. Penciclovir (active metabolite from famciclovir) and 6-deoxypenciclovir (first intermediate metabolite from famciclovir) were determined by using LC/MS/MS method. The limit of quantification was 0.15 µg/mL For both compounds. Calculations were done in WinNonlin 5.0.1, using non-compartmental methods.
Outcome measures
| Measure |
Famciclovir (Participants Aged 12 to Less Than [<] 15 Years)
n=8 Participants
Participants aged 12 to \<15 years received single oral doses of three 500 milligrams (mg) Famciclovir tablets on Day 1.
|
Famciclovir (Participants Aged 15 to Less Than [<] 18 Years)
n=6 Participants
Participants aged 15 to \<18 years received single oral doses of three 500 milligrams (mg) Famciclovir tablets on Day 1.
|
|---|---|---|
|
Apparent Terminal Elimination Half-Life (T½) of Penciclovir (Active Metabolite From Famciclovir) and 6-deoxypenciclovir (First Intermediate Metabolite From Famciclovir)
|
1.81 Hours
Standard Deviation 0.22
|
0.78 Hours
Standard Deviation 0.21
|
SECONDARY outcome
Timeframe: Pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6 and 10 hours Post-dosePopulation: The analysis was performed in PK (Pharmacokinetics) analysis set (PAS) population, defined as all participants who participated in the PK assessment part and who did not miss more than one PK blood sampling. Here, number of participants analyzed refer to the number of participants evaluable for this outcome at specified time point.
CL/F was defined as the apparent oral clearance of penciclovir from plasma = dose of famciclovir\*0.7884/AUC 0-inf, where 0.7884 is the ratio of the molecular weight of penciclovir (253.3 g/mol) to famciclovir (321.3 g/mol). F is the bioavailability of penciclovir after oral administration of famciclovir. Penciclovir (active metabolite from famciclovir) and 6-deoxypenciclovir (first intermediate metabolite from famciclovir) were determined by using LC/MS/MS method. The limit of quantification was 0.15 µg/mL for both compounds. Calculations were done in WinNonlin 5.0.1, using non-compartmental methods.
Outcome measures
| Measure |
Famciclovir (Participants Aged 12 to Less Than [<] 15 Years)
n=8 Participants
Participants aged 12 to \<15 years received single oral doses of three 500 milligrams (mg) Famciclovir tablets on Day 1.
|
Famciclovir (Participants Aged 15 to Less Than [<] 18 Years)
Participants aged 15 to \<18 years received single oral doses of three 500 milligrams (mg) Famciclovir tablets on Day 1.
|
|---|---|---|
|
Apparent Oral Clearance of Penciclovir From Plasma (CL/F) of Penciclovir (Active Metabolite From Famciclovir)
|
38.2 Litres(L)/Hour(h)
Standard Deviation 6.1
|
—
|
Adverse Events
Famciclovir (Participants Aged 12 to Less Than [<] 15 Years)
Famciclovir (Participants Aged 15 to Less Than [<] 18 Years)
Famciclovir
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Famciclovir (Participants Aged 12 to Less Than [<] 15 Years)
n=28 participants at risk
Participants aged 12 to \<15 years received single oral doses of three 500 milligrams (mg) Famciclovir tablets on Day 1.
|
Famciclovir (Participants Aged 15 to Less Than [<] 18 Years)
n=25 participants at risk
Participants aged 15 to \<18 years received single oral doses of three 500 milligrams (mg) Famciclovir tablets on Day 1.
|
Famciclovir
n=53 participants at risk
Participants received single oral doses of three 500 milligrams (mg) Famciclovir tablets on Day 1.
|
|---|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
0.00%
0/28 • From Start of the Study up to Day 36.
|
4.0%
1/25 • From Start of the Study up to Day 36.
|
1.9%
1/53 • From Start of the Study up to Day 36.
|
|
Blood and lymphatic system disorders
Lymphadenopathy
|
0.00%
0/28 • From Start of the Study up to Day 36.
|
4.0%
1/25 • From Start of the Study up to Day 36.
|
1.9%
1/53 • From Start of the Study up to Day 36.
|
|
Gastrointestinal disorders
Abdominal pain upper
|
3.6%
1/28 • From Start of the Study up to Day 36.
|
0.00%
0/25 • From Start of the Study up to Day 36.
|
1.9%
1/53 • From Start of the Study up to Day 36.
|
|
Gastrointestinal disorders
Diarrhoea
|
3.6%
1/28 • From Start of the Study up to Day 36.
|
0.00%
0/25 • From Start of the Study up to Day 36.
|
1.9%
1/53 • From Start of the Study up to Day 36.
|
|
Gastrointestinal disorders
Nausea
|
3.6%
1/28 • From Start of the Study up to Day 36.
|
0.00%
0/25 • From Start of the Study up to Day 36.
|
1.9%
1/53 • From Start of the Study up to Day 36.
|
|
Gastrointestinal disorders
Vomiting
|
3.6%
1/28 • From Start of the Study up to Day 36.
|
0.00%
0/25 • From Start of the Study up to Day 36.
|
1.9%
1/53 • From Start of the Study up to Day 36.
|
|
General disorders
Fatigue
|
3.6%
1/28 • From Start of the Study up to Day 36.
|
0.00%
0/25 • From Start of the Study up to Day 36.
|
1.9%
1/53 • From Start of the Study up to Day 36.
|
|
Nervous system disorders
Dizziness
|
0.00%
0/28 • From Start of the Study up to Day 36.
|
12.0%
3/25 • From Start of the Study up to Day 36.
|
5.7%
3/53 • From Start of the Study up to Day 36.
|
|
Nervous system disorders
Headache
|
3.6%
1/28 • From Start of the Study up to Day 36.
|
4.0%
1/25 • From Start of the Study up to Day 36.
|
3.8%
2/53 • From Start of the Study up to Day 36.
|
|
Renal and urinary disorders
Pollakiuria
|
3.6%
1/28 • From Start of the Study up to Day 36.
|
0.00%
0/25 • From Start of the Study up to Day 36.
|
1.9%
1/53 • From Start of the Study up to Day 36.
|
|
Renal and urinary disorders
Pyuria
|
0.00%
0/28 • From Start of the Study up to Day 36.
|
4.0%
1/25 • From Start of the Study up to Day 36.
|
1.9%
1/53 • From Start of the Study up to Day 36.
|
|
Reproductive system and breast disorders
Dysmenorrhoea
|
3.6%
1/28 • From Start of the Study up to Day 36.
|
0.00%
0/25 • From Start of the Study up to Day 36.
|
1.9%
1/53 • From Start of the Study up to Day 36.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place