A PROSPECTIVE, OPEN-LABEL, NON-COMPARATIVE STUDY TO ASSESS THE SAFETY, TOLERABILITY AND EFFICACY OF VORICONAZOLE FOR THE PRIMARY AND SALVAGE TREATMENT OF INVASIVE CANDIDIASIS, CANDIDEMIA, AND ESOPHAGEAL CANDIDIASIS IN PEDIATRIC SUBJECTS

• Register: EUCTR
• Last refreshed on: 15 July 2013
• Main ID: EUCTR2009-012848-16-HU
• Date of registration: 23/02/2010
• Prospective Registration: Yes
• Primary sponsor: Pfizer Inc., 235 East 42nd Street, New York, NY 10017
• Public title: A PROSPECTIVE, OPEN-LABEL, NON-COMPARATIVE STUDY TO ASSESS THE SAFETY, TOLERABILITY AND EFFICACY OF VORICONAZOLE FOR THE PRIMARY AND SALVAGE TREATMENT OF INVASIVE CANDIDIASIS, CANDIDEMIA, AND ESOPHAGEAL CANDIDIASIS IN PEDIATRIC SUBJECTS
• Scientific title: A PROSPECTIVE, OPEN-LABEL, NON-COMPARATIVE STUDY TO ASSESS THE SAFETY, TOLERABILITY AND EFFICACY OF VORICONAZOLE FOR THE PRIMARY AND SALVAGE TREATMENT OF INVASIVE CANDIDIASIS, CANDIDEMIA, AND ESOPHAGEAL CANDIDIASIS IN PEDIATRIC SUBJECTS
• Date of first enrolment: 24/03/2010
• Target sample size: 96
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2009-012848-16
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: no Open: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: Placebo: Other:

Countries of recruitment

Bulgaria, Czech Republic, Germany, Hungary, Romania

Key inclusion & exclusion criteria

Inclusion criteria:
•Male or female 2 to<18 yrs of age;
•A personally signed and dated informed consent document indicating that a legally authorized representative has been informed of all pertinent aspects of the study. Assent will be required for children per local regulations or/and for those who are able to comprehend;
•Willing and able to comply with the scheduled visits, treatment plan, laboratory tests, and other study procedures;
•A diagnosis of invasive candidiasis/candidemia (ICC) or esophageal candidiasis(EC);
•Therapy with voriconazole must be considered an appropriate treatment option by the investigator.
Primary ICC: the following two criteria must be met:
1. Must have at least one of the following:
•At least one positive blood culture or culture from a normally sterile site for yeast (later confirmed as Candida sp.) or for Candida sp. within the previous 7 days prior to the first dose of study medication; or
•Histopathologic/direct microscopic evidence suggestive of Candida sp. (later confirmed as Candida sp.) from at least one specimen obtained from a normally sterile site within the previous 7 days prior to the first dose of study medication; or
•At least one positive culture for yeast (later confirmed as Candida sp.) or Candida sp. from a drain placed <24 hours within the previous 7 days prior to the first dose of study medication; or
•New radiologic findings consistent with disseminated disease after a positive culture for Candida sp. within the previous 14 days prior to enrollment.
2. Must have at least one of the following:
•Fever (oral or tympanic or axillary) temperature =38.0°C (100.4°F)); or
•Hypothermia (temperature <36.0°C (96.8°F)); or
•SBP less than 100 mmHg,or a decrease in SBP of at least 30 mmHg from baseline; or
•Site specific signs and symptoms of Candida infection; or
•Radiologic findings consistent with Candida infection.
Salvage ICC: the following two criteria are met:
1. Must have at least one of the following:
•At least one positive blood culture or culture from a normally sterile site for yeast (later confirmed as Candida sp.) or for Candida sp. within the previous 14 days prior to the first dose of study medication; or
•Histopathologic/direct microscopic evidence suggestive of Candida sp. (later confirmed as Candida sp.) from at least one specimen obtained from a normally sterile site within the previous 14 days prior to prior to the first dose of study medication; or
•At least one positive culture for yeast (later confirmed as Candida sp.) or for Candida sp. from a drain placed <24 hours, within the previous 14 days prior to the first dose of study medication; or
•New radiologic findings consistent with disseminated disease after a positive culture for Candida sp. within the previous 14 days prior to enrollment.
2. Must have had a clinical and/or microbiologic response deemed as unsatisfactory to at least one other antifungal after at least 7 days of therapy at clinically recognized effective doses.
Primary EC: all of the following three criteria must be met:
•Must have clinical symptoms consistent with esophageal candidiasis, such as dysphagia, odynophagia and retrosternal pain, with or without concomitant oropharyngeal candidiasis withing the previous 7 days prior to enrollment.
•Must have lesions characteristic of esophageal candidiasis visualized by esophagoscopy within the previous 7 days prior to enrollment.
•Must have positive microscopy and/or mycological culture for yeast (later confirmed as Candi
Exclusion criteria:
Subjects presenting with any of the following exclusions will not be included in the study:
1. Known allergy, serious reaction, or hypersensitivity to voriconazole or its excipients, or any azole antifungal agent.
2. Females who are pregnant, lactating (breast feeding) or planning a pregnancy during the course of the study, or who are of childbearing potential and not using highly effective method of birth control (eg, surgically sterile, intrauterine device, oral contraceptive plus barrier contraceptive, hormone delivery system plus barrier contraceptive, or condom in combination with contraceptive cream, jelly, or foam).
Subjects are to continue contraceptive methods during the study and for at least 30 days after receiving their last treatment.
3. Subjects receiving, or are likely to receive, any Phase I investigational drug. (Note: Subjects receiving Phase II or III investigational drugs may be enrolled only with the prior approval of the Sponsor's medical monitor. Subjects receiving investigational drugs that are currently licensed for other indications may be enrolled).
4. Subjects who have received drugs that may cause QT interval prolongation within 24 hours prior to enrollment. Including, but not limited to, the following: terfenadine, astemizole, cisapride, pimozide, or quinidine.
5. Requiring continued treatment with another systemic antifungal agent.
6. Concomitantly receiving one of the following drugs: sirolimus, rifampin, rifabutin, carbamazepine, long-acting barbiturates (eg, phenobarbital, mephobarbital), ritonavir, efavirenz, or ergot alkaloids (eg, ergotamine, dihydroergotamine).
7. Concomitantly receiving drugs with clinically relevant drug interactions with voriconazole, unless closely monitored or dosage adjusted as clarified in Appendix 1.
8. Poor venous access or other considerations that would preclude intravenous drug delivery or blood sampling.
9. For Primary Therapy: Subjects who have received more than 48 hours antifungal
therapy (prior to the first dose of study drug) for the treatment of an active fungal infection. ** Please note ** Subjects receiving antifungal agents for the prophylaxis (eg, for the prevention of fungal infection) prior to and up to the time of enrollment are eligible to participate in the study.
10. Liver dysfunction, at baseline, defined as total bilirubin, AST, ALT, or alkaline phosphatase >5 times the upper limit of normal. Note: If laboratory values drawn at the screening visit (prior to the first dose of study medication) exceeds the above limits for exclusion, the Sponsor's medical monitor must be contacted without delay to discuss enrollment and initiation of study treatment.
11. Subjects with moderate or severe renal impairment (creatinine clearance <50 mL/min), unless an assessment of the benefit/risk to the subject justifies the use of intravenous voriconazole. A subject with moderate or severe renal impairment may be enrolled only with prior approval of the Sponsor's medical monitor.
? Creatinine Clearance will be calculated using the Schwartz formula.
? Creatinine Clearance (mL/min) = [k x height (cm)]/serum creatinine (mg/dL).
Where k = 0.55 for either gender =12 years of age; k =0.55 for females 13 to 21 years of age; and k = 0.7 for males 13 to 21 years of age. Note: Other methods of calculation creatinine clearance (eg, 24-hr urine creatinine collection) are permissible.
12. Subjects with prosthetic devices and/or vascular catheters (eg, central venous catheter, implant

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Invasive candidiasis, including candidemia (ICC), and esophageal candidiasis (EC)
MedDRA version: 12.0 Level: LLT Classification code 10007161 Term: Candidiasis of the esophagus
MedDRA version: 12.0 Level: LLT Classification code 10060573 Term: Candidemia
MedDRA version: 12.0 Level: LLT Classification code 10064954 Term: Invasive candidiasis

Intervention(s)

Trade Name: Vfend
Pharmaceutical Form: Tablet
INN or Proposed INN: Voriconazole
Other descriptive name: (2R, 3S)-2-(2,4-difluorophenyl)-3-(5-fluoro-4-pyrimidinyl)-1-(1H-1,2,4-triazol-1-yl)-2-butanol
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 50-

Trade Name: Vfend
Pharmaceutical Form: Tablet
INN or Proposed INN: Voriconazole
Other descriptive name: (2R, 3S)-2-(2,4-difluorophenyl)-3-(5-fluoro-4-pyrimidinyl)-1-(1H-1,2,4-triazol-1-yl)-2-butanol
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 200-

Trade Name: Vfend
Pharmaceutical Form: Powder for solution for infusion
INN or Proposed INN: Voriconazole
Other descriptive name: (2R, 3S)-2-(2,4-difluorophenyl)-3-(5-fluoro-4-pyrimidinyl)-1-(1H-1,2,4-triazol-1-yl)-2-butanol
Concentration unit: mg/g milligram(s)/gram
Concentration type: equal
Concentration number: 200-

Trade Name: Vfend
Pharmaceutical Form: Powder for oral suspension
INN or Proposed INN: Voriconazole
Other descriptive name: (2R, 3S)-2-(2,4-difluorophenyl)-3-(5-fluoro-4-pyrimidinyl)-1-(1H-1,2,4-triazol-1-yl)-2-butanol
Concentration unit: mg/l milligram(s)/litre
Concentration type: equal
Concentration number: 40-

Primary Outcome(s)

Secondary Objective: ? To assess the efficacy of voriconazole for the treatment of invasive candidiasis, including candidemia, and esophageal candidiasis in pediatric subjects 2 to <18 years of age.
? To assess time to death and all-cause mortality during study therapy, at Day 28, and at the one month follow-up visit.

Main Objective: To assess the safety and tolerability of voriconazole for the treatment of invasive candidiasis, including candidemia, and esophageal candidiasis in pediatric subjects 2 to <18 years of age.

Primary end point(s): Safety and tolerability of voriconazole, as determined by the rate of adverse events (serious and non-serious), including visual-, cardiac-, and liver-related adverse effects, and treatment discontinuation.

Secondary ID(s)

A1501085

2009-012848-16-DE