Safety and Pharmacokinetics of Famciclovir Single 1500 mg Dose in Adolescents With Recurrent Herpes Labialis

A Multicenter, Open-label, Single-arm Study to Evaluate the Safety and Pharmacokinetics of Famciclovir Single 1500 mg Dose in Adolescents With Recurrent Herpes Labialis

Status

Completed

Phases

Phase 2Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00878072

Enrollment

Registered

2009-04-08

Start date

2009-03-25

Completion date

2010-06-02

Last updated

2021-06-25

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Herpes Labialis

Keywords

Herpes labialis, cold sores, herpes simplex type 1

Brief summary

This study will assess the safety, tolerability of a single 1500 mg dose of famciclovir in 50 adolescents with recurrent herpes labialis. Eight of the 50 adolescents will also participate in the pharmacokinetics (PK) assessment of famciclovir single 1500 mg dose

Detailed description

Uncontrolled study

Interventions

DRUGFamciclovir

Famciclovir 1500 mg (3 x 500 mg tablets) oral as a single dose.

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

12 Years to 18 Years

Healthy volunteers

Inclusion criteria

* Outpatient males or females 12 to \<18 years of age * General good health with a documented history typical for recurrent herpes labialis * Prodromal symptoms or active lesions suggestive of a recurrent episode of herpes labialis (i.e. having had cold sores in the past) , with onset not exceeding 24 hours until the time of study drug administration * Adolescents participating in Pharmacokinetics (PK) part of the study may be enrolled without an active herpes labialis recurrence or with onset of signs/symptoms of a recurrent herpes labialis episode longer than 24 hours before study drug administration, All adolescents participating in the pharmacokinetics assessments must fast for at least 8 hours prior to Visit 1 and be willing to fast for an additional 2 hours after study drug administration

Exclusion criteria

* Use of other investigational drugs within 30 days of enrollment * History of hypersensitivity to famciclovir or penciclovir * Inability to swallow tablets * Body weight less than 40 Killograms (kg) * History of malabsorption, unless a condition like celiac disease is stable and well controlled, previous gastrointestinal surgery or radiation therapy that could affect drug absorption or metabolism, or any condition that could interfere with drug absorption, distribution, metabolism, or excretion * Known renal insufficiency (calculated creatinine clearance \<60 \[Milliliters/Minutes\] mL/min) * Known severe hepatic impairment (Child-Pugh Class C) * Significant skin disease such as atopic dermatitis or eczema that would interfere with assessment of oral/labial lesions * Known to be immunocompromised or are receiving systemic or using topical immunosuppressive agents (including corticosteroids, tacrolimus and picrolimus) within 30 days of enrollment * Concomitant use of probenecid * Pregnant or nursing (lactating) females * Females of child-bearing potential, UNLESS they are using two birth control methods. The two methods can be a double barrier method or a barrier method plus a hormonal method.

Design outcomes

Primary

Measure	Time frame	Description
Number of Participants Reported Adverse Events (AEs), Serious Adverse Events (SAEs)	From Start of the Study up to Day 36	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.
Number of Participants With Clinically Significant Laboratory Abnormalities	From Start of the Study up to Day 36	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 .

Secondary

Measure	Time frame	Description
Area Under the Plasma Concentration of Penciclovir (Active Metabolite From Famciclovir) and 6-deoxypenciclovir (First Intermediate Metabolite From Famciclovir)	Pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6 and 10 hours Post-dose	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.
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)	Pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6 and 10 hours Post-dose	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.
Time of Maximum Observed Plasma Concentration (Tmax) of Penciclovir (Active Metabolite From Famciclovir) and 6-deoxypenciclovir (First Intermediate Metabolite From Famciclovir)	Pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6 and 10 hours Post-dose	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.
Apparent Oral Clearance of Penciclovir From Plasma (CL/F) of Penciclovir (Active Metabolite From Famciclovir)	Pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6 and 10 hours Post-dose	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.
Apparent Terminal Elimination Half-Life (T½) of Penciclovir (Active Metabolite From Famciclovir) and 6-deoxypenciclovir (First Intermediate Metabolite From Famciclovir)	Pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6 and 10 hours Post-dose	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.
Maximum Plasma Concentration (Cmax) of Penciclovir (Active Metabolite From Famciclovir) and 6-deoxypenciclovir (First Intermediate Metabolite From Famciclovir)	Pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6 and 10 hours Post-dose	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.

Countries

United States

Participant flow

Recruitment details

The study was conducted at 10 centers in United States.

Participants by arm

Arm	Count
Famciclovir Participants received single oral doses of three 500 milligrams (mg) Famciclovir tablets on Day 1.	53
Total	53

Withdrawals & dropouts

Period	Reason	FG000
Overall Study	Withdrew consent	2

Baseline characteristics

Characteristic	Famciclovir
Age, Continuous	14.4 years STANDARD_DEVIATION 1.86
Sex: Female, Male Female	33 Participants
Sex: Female, Male Male	20 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk
deaths Total, all-cause mortality	0 / 28	0 / 25	0 / 53
other Total, other adverse events	6 / 28	6 / 25	12 / 53
serious Total, serious adverse events	0 / 28	0 / 25	0 / 53

Outcome results

Primary

Number of Participants Reported Adverse Events (AEs), Serious Adverse Events (SAEs)

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.

Time frame: From Start of the Study up to Day 36

Population: 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.

Arm	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
Famciclovir (Participants Aged 12 to Less Than [<] 15 Years)	Number of Participants Reported Adverse Events (AEs), Serious Adverse Events (SAEs)	Adverse Events	6 Participants
Famciclovir (Participants Aged 12 to Less Than [<] 15 Years)	Number of Participants Reported Adverse Events (AEs), Serious Adverse Events (SAEs)	Serious Adverse Events	0 Participants
Famciclovir (Participants Aged 15 to Less Than [<] 18 Years)	Number of Participants Reported Adverse Events (AEs), Serious Adverse Events (SAEs)	Adverse Events	6 Participants
Famciclovir (Participants Aged 15 to Less Than [<] 18 Years)	Number of Participants Reported Adverse Events (AEs), Serious Adverse Events (SAEs)	Serious Adverse Events	0 Participants

Primary

Number of Participants With Clinically Significant Laboratory Abnormalities

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 .

Time frame: From Start of the Study up to Day 36

Population: 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.

Arm	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
Famciclovir (Participants Aged 12 to Less Than [<] 15 Years)	Number of Participants With Clinically Significant Laboratory Abnormalities	Hematology	0 Participants
Famciclovir (Participants Aged 12 to Less Than [<] 15 Years)	Number of Participants With Clinically Significant Laboratory Abnormalities	Clinical chemistry	0 Participants
Famciclovir (Participants Aged 12 to Less Than [<] 15 Years)	Number of Participants With Clinically Significant Laboratory Abnormalities	Urinalysis	0 Participants
Famciclovir (Participants Aged 15 to Less Than [<] 18 Years)	Number of Participants With Clinically Significant Laboratory Abnormalities	Hematology	0 Participants
Famciclovir (Participants Aged 15 to Less Than [<] 18 Years)	Number of Participants With Clinically Significant Laboratory Abnormalities	Clinical chemistry	0 Participants
Famciclovir (Participants Aged 15 to Less Than [<] 18 Years)	Number of Participants With Clinically Significant Laboratory Abnormalities	Urinalysis	0 Participants

Secondary

Apparent Oral Clearance of Penciclovir From Plasma (CL/F) of Penciclovir (Active Metabolite From Famciclovir)

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.