Non-Interventional Post Marketing Surveillance Study To Observe The Safety And Efficacy Of Vfend® Tablet In Korea

• Sponsor: Pfizer (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01073631
• Collaborator: (none)
• Enrollment: 543
• Duration (Months): 43

Study Details

Study Description

Brief Summary

This is a non-interventional study of voriconazole tablet in Korea which is mandated by the Korean government agency.

Condition or Disease	Intervention/Treatment	Phase
Serious Fungal Infections	Drug: voriconazole tablet

Study Design

• Study Type: Observational
• Actual Enrollment: 543 participants
• Observational Model: Case-Only
• Time Perspective: Prospective
• Official Title: Post Marketing Surveillance Study To Observe The Safety And Efficacy Of Vfend® Tablet
• Study Start Date: Mar 1, 2006
• Actual Primary Completion Date: Oct 1, 2009
• Actual Study Completion Date: Oct 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
1 Patients who are indicated for use of voriconazole tablet.	Drug: voriconazole tablet; 200 mg PO bid (orally, twice a day); Other Names: Vfend

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants With Categorical Clinical Response: Cure, Improvement, Failure, or Unevaluable [Baseline (Day 1) up to 2.1 Years]

   Clinical response defined as: Cure=resolution of all baseline signs and symptoms of fungal infection(s); Improvement=lessening of baseline signs and symptoms or absence of one or more, but not all baseline findings; Failure=no improvement or deterioration of baseline condition; Unevaluable=incomplete therapy (efficacy could not be evaluated or discontinuation was not followed up).

Secondary Outcome Measures

1. Percentage of Participants With Cultivated Strain Mycological Response: Eradication, Persistence, Superinfection, or Not Evaluable [Baseline (Day 1) up to 2.1 Years]

   In case cultivation performed, cultivated strain before and after Vfend administration recorded, and the improvement of mycological outcomes after administration evaluated. Mycological response defined as: Eradication=absence of signs and symptoms of fungal infection; Persistence=(no eradication) presence of fungal infection; Superinfection=existence of different strains from strains separated prior to study treatment; Not evaluable=a follow-up mycological cultivation not performed.

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Patients who are indicated for voriconazole table according to the drug package insert.

Exclusion Criteria:

• None.

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Pfizer

Investigators

• Study Director: Pfizer CT.gov Call Center, Pfizer

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• To obtain contact information for a study center near you, click here.

Publications

None provided.

• Responsible Party: Pfizer
• ClinicalTrials.gov Identifier: NCT01073631
• Other Study ID Numbers: A1501068
• First Posted: Feb 23, 2010
• Last Update Posted: Jun 7, 2012
• Last Verified: May 1, 2012

• Keywords provided by Pfizer: voriconazole; Korea; invasive fungal infection
• Additional relevant MeSH terms: Mycoses; Voriconazole

Study Results

Participant Flow

Pre-assignment Detail	There were 543 participants enrolled in this study. Of these, 230 participants were treated with the Vfend tablet formulation only, and 313 participants were treated with Vfend tablet and Vfend intravenous (IV) formulations sequentially or vice versa. These 313 participants are also included in Study A1501067 (NCT01073618).

Arm/Group Title	Vfend
Arm/Group Description	Vfend (voriconazole) tablets (recommended dose: 200mg orally every 12hours) or sequential Vfend tablet and IV Vfend (recommended dose: 6mg/kg IV infusion every 12hours for first 24hours [loading dose], 3 to 4mg/kg IV infusion every 12hours [maintenance dose]) treatment (or vice versa) for use as indicated according to approved local product document and adjusted according to medical and therapeutic necessity.
Period Title: Overall Study
STARTED	543
COMPLETED	374
NOT COMPLETED	169

Baseline Characteristics

Arm/Group Title	Vfend
Arm/Group Description	Vfend (voriconazole) tablets (recommended dose: 200mg orally every 12hours) or sequential Vfend tablet and IV Vfend (recommended dose: 6mg/kg IV infusion every 12hours for first 24hours [loading dose], 3 to 4mg/kg IV infusion every 12hours [maintenance dose]) treatment (or vice versa) for use as indicated according to approved local product document and adjusted according to medical and therapeutic necessity.
Overall Participants	543
Age, Customized (Number) [Number]
<18 years	74 13.6%
Between 18 and 44 years	157 28.9%
Between 45 and 64 years	207 38.1%
>=65 years	105 19.3%
Sex: Female, Male (Count of Participants)
Female	211 38.9%
Male	332 61.1%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With Categorical Clinical Response: Cure, Improvement, Failure, or Unevaluable
Description	Clinical response defined as: Cure=resolution of all baseline signs and symptoms of fungal infection(s); Improvement=lessening of baseline signs and symptoms or absence of one or more, but not all baseline findings; Failure=no improvement or deterioration of baseline condition; Unevaluable=incomplete therapy (efficacy could not be evaluated or discontinuation was not followed up).
Time Frame	Baseline (Day 1) up to 2.1 Years

Outcome Measure Data

Analysis Population Description

Safety population: participants received at least 1 dose of study drug for approved indication (= Intent to treat [ITT] population plus all unevaluable participants); ITT=participants received study drug for the approved indication and had been evaluated for related paramenters at least once.

Arm/Group Title	Vfend
Arm/Group Description	Vfend (voriconazole) tablets (recommended dose: 200mg orally every 12hours) or sequential Vfend tablet and IV Vfend (recommended dose: 6mg/kg IV infusion every 12hours for first 24hours [loading dose], 3 to 4mg/kg IV infusion every 12hours [maintenance dose]) treatment (or vice versa) for use as indicated according to approved local product document and adjusted according to medical and therapeutic necessity.
Measure Participants	543
Cure	36.83 6.8%
Improvement	26.52 4.9%
Failure	16.94 3.1%
Unevaluable	19.71 3.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Vfend
	Comments	Efficacy Rate (treatment effective) = Percentage of evaluable participants with clinical response of cure or improvement
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Efficacy rate (percent)
	Estimated Value	78.90
	Confidence Interval	(2-Sided) 95%; 75.07 to 82.73
	Parameter Dispersion	Type: Value:
	Estimation Comments	Confidence Interval (CI) by normal approximation to binomial.

2. Secondary Outcome

Title	Percentage of Participants With Cultivated Strain Mycological Response: Eradication, Persistence, Superinfection, or Not Evaluable
Description	In case cultivation performed, cultivated strain before and after Vfend administration recorded, and the improvement of mycological outcomes after administration evaluated. Mycological response defined as: Eradication=absence of signs and symptoms of fungal infection; Persistence=(no eradication) presence of fungal infection; Superinfection=existence of different strains from strains separated prior to study treatment; Not evaluable=a follow-up mycological cultivation not performed.
Time Frame	Baseline (Day 1) up to 2.1 Years

Outcome Measure Data

Analysis Population Description

ITT; N=number of participants evaluated for mycological response.

Arm/Group Title	Vfend
Arm/Group Description	Vfend (voriconazole) tablets (recommended dose: 200mg orally every 12hours) or sequential Vfend tablet and IV Vfend (recommended dose: 6mg/kg IV infusion every 12hours for first 24hours [loading dose], 3 to 4mg/kg IV infusion every 12hours [maintenance dose]) treatment (or vice versa) for use as indicated according to approved local product document and adjusted according to medical and therapeutic necessity.
Measure Participants	88
Eradication	71.59 13.2%
Persistence	23.86 4.4%
Superinfection	2.27 0.4%
Not evaluable	2.27 0.4%

Adverse Events

Time Frame	Treatment emergent adverse events are reported from the time of the first dose of study treatment up to 28 days after last dose of study treatment.
Adverse Event Reporting Description	The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Arm/Group Title	Vfend
Arm/Group Description	Vfend (voriconazole) tablets (recommended dose: 200mg orally every 12hours) or sequential Vfend tablet and IV Vfend (recommended dose: 6mg/kg IV infusion every 12hours for first 24hours [loading dose], 3 to 4mg/kg IV infusion every 12hours [maintenance dose]) treatment (or vice versa) for use as indicated according to approved local product document and adjusted according to medical and therapeutic necessity.
All Cause Mortality
	Vfend
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Vfend
	Affected / at Risk (%)	# Events
Total	119/543 (21.9%)
Blood and lymphatic system disorders
Disseminated intravascular coagulation	3/543 (0.6%)
Febrile neutropenia	1/543 (0.2%)
Thrombocytopenia	3/543 (0.6%)
Thrombotic microangiopathy	1/543 (0.2%)
Cardiac disorders
Arrhythmia	1/543 (0.2%)
Cardiac arrest	1/543 (0.2%)
Cardiac failure	1/543 (0.2%)
Cardiopulmonary failure	1/543 (0.2%)
Left ventricular dysfunction	1/543 (0.2%)
Supraventricular tachycardia	1/543 (0.2%)
Congenital, familial and genetic disorders
Tracheo-oesophageal fistula	1/543 (0.2%)
Endocrine disorders
Euthyroid sick syndrome	1/543 (0.2%)
Gastrointestinal disorders
Colitis	1/543 (0.2%)
Gastric perforation	1/543 (0.2%)
Gastric ulcer	1/543 (0.2%)
Gastrointestinal haemorrhage	1/543 (0.2%)
Neutropenic colitis	1/543 (0.2%)
Abdominal pain upper	1/543 (0.2%)
Erosive oesophagitis	1/543 (0.2%)
General disorders
Death	1/543 (0.2%)
Disease progression	3/543 (0.6%)
Multi-organ failure	6/543 (1.1%)
Oedema peripheral	2/543 (0.4%)
Pyrexia	5/543 (0.9%)
Hepatobiliary disorders
Cholecystitis	1/543 (0.2%)
Cholecystitis acute	1/543 (0.2%)
Hepatitis	1/543 (0.2%)
Jaundice	1/543 (0.2%)
Hepatic failure	1/543 (0.2%)
Hepatic function abnormal	1/543 (0.2%)
Hepatitis acute	1/543 (0.2%)
Hepatotoxicity	1/543 (0.2%)
Immune system disorders
Acute graft versus host disease in intestine	2/543 (0.4%)
Acute graft versus host disease in skin	2/543 (0.4%)
Infections and infestations
Anal abscess	1/543 (0.2%)
Aspergillosis	4/543 (0.7%)
Bronchitis	1/543 (0.2%)
Cytomegalovirus infection	2/543 (0.4%)
Enterococcal infection	1/543 (0.2%)
Fungal infection	1/543 (0.2%)
Infection	1/543 (0.2%)
Liver abscess	1/543 (0.2%)
Pneumonia	21/543 (3.9%)
Pneumonia staphylococcal	1/543 (0.2%)
Pseudomembranous colitis	1/543 (0.2%)
Sepsis	15/543 (2.8%)
Septic shock	18/543 (3.3%)
Cellulitis	1/543 (0.2%)
Central nervous system infection	1/543 (0.2%)
Citrobacter sepsis	1/543 (0.2%)
Cytomegalovirus chorioretinitis	1/543 (0.2%)
Device related infection	1/543 (0.2%)
Pneumonia fungal	1/543 (0.2%)
Injury, poisoning and procedural complications
Chemical peritonitis	1/543 (0.2%)
Investigations
Cytomegalovirus test positive	1/543 (0.2%)
Oxygen saturation decreased	1/543 (0.2%)
Acoustic stimulation tests	1/543 (0.2%)
Metabolism and nutrition disorders
Hyperkalaemia	1/543 (0.2%)
Metabolic acidosis	1/543 (0.2%)
Dehydration	1/543 (0.2%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Acute myeloid leukaemia	3/543 (0.6%)
Diffuse large B-cell lymphoma	1/543 (0.2%)
Leukaemia	12/543 (2.2%)
Lymphoma	1/543 (0.2%)
Nervous system disorders
Cerebellar infarction	1/543 (0.2%)
Cerebral haemorrhage	2/543 (0.4%)
Convulsion	2/543 (0.4%)
Grand mal convulsion	1/543 (0.2%)
Intracranial pressure increased	1/543 (0.2%)
Mental impairment	1/543 (0.2%)
Psychiatric disorders
Completed suicide	1/543 (0.2%)
Renal and urinary disorders
Azotaemia	1/543 (0.2%)
Cystitis haemorrhagic	3/543 (0.6%)
Renal failure acute	4/543 (0.7%)
Renal impairment	1/543 (0.2%)
Nephropathy toxic	1/543 (0.2%)
Renal failure	1/543 (0.2%)
Renal failure chronic	1/543 (0.2%)
Respiratory, thoracic and mediastinal disorders
Acute pulmonary oedema	1/543 (0.2%)
Acute respiratory distress syndrome	2/543 (0.4%)
Dyspnoea	6/543 (1.1%)
Haemoptysis	2/543 (0.4%)
Hypoxia	3/543 (0.6%)
Pneumothorax	2/543 (0.4%)
Pulmonary embolism	1/543 (0.2%)
Pulmonary haemorrhage	3/543 (0.6%)
Respiratory failure	3/543 (0.6%)
Vascular disorders
Haemorrhage	1/543 (0.2%)
Shock	1/543 (0.2%)
Other (Not Including Serious) Adverse Events
	Vfend
	Affected / at Risk (%)	# Events
Total	154/543 (28.4%)
Blood and lymphatic system disorders
Anaemia	1/543 (0.2%)
Eosinophilia	1/543 (0.2%)
Febrile neutropenia	2/543 (0.4%)
Neutropenia	7/543 (1.3%)
Pancytopenia	1/543 (0.2%)
Thrombocytopenia	5/543 (0.9%)
Cardiac disorders
Atrial fibrillation	1/543 (0.2%)
Left ventricular dysfunction	1/543 (0.2%)
Tachycardia	1/543 (0.2%)
Angina pectoris	1/543 (0.2%)
Ear and labyrinth disorders
Otorrhoea	1/543 (0.2%)
Endocrine disorders
Adrenal insufficiency	1/543 (0.2%)
Eye disorders
Eye disorder	1/543 (0.2%)
Eye pain	1/543 (0.2%)
Keratoconjunctivitis sicca	1/543 (0.2%)
Ocular hyperaemia	1/543 (0.2%)
Vision blurred	2/543 (0.4%)
Visual acuity reduced	3/543 (0.6%)
Visual impairment	6/543 (1.1%)
Gastrointestinal disorders
Abdominal pain	2/543 (0.4%)
Abdominal pain upper	1/543 (0.2%)
Constipation	5/543 (0.9%)
Diarrhoea	5/543 (0.9%)
Dyspepsia	1/543 (0.2%)
Gastric ulcer	1/543 (0.2%)
Gastritis haemorrhagic	1/543 (0.2%)
Haematochezia	1/543 (0.2%)
Haemorrhoids	1/543 (0.2%)
Mouth haemorrhage	1/543 (0.2%)
Nausea	5/543 (0.9%)
Oesophagitis	1/543 (0.2%)
Perianal erythema	1/543 (0.2%)
Reflux oesophagitis	1/543 (0.2%)
Stomatitis	4/543 (0.7%)
Vomiting	8/543 (1.5%)
General disorders
Chest discomfort	1/543 (0.2%)
Feeling abnormal	1/543 (0.2%)
Influenza like illness	1/543 (0.2%)
Oedema	1/543 (0.2%)
Oedema peripheral	1/543 (0.2%)
Pain	2/543 (0.4%)
Pyrexia	18/543 (3.3%)
Hepatobiliary disorders
Hepatic function abnormal	1/543 (0.2%)
Hepatitis	1/543 (0.2%)
Hepatitis toxic	1/543 (0.2%)
Hepatotoxicity	1/543 (0.2%)
Hyperbilirubinaemia	2/543 (0.4%)
Immune system disorders
Acute graft versus host disease in intestine	2/543 (0.4%)
Graft versus host disease	2/543 (0.4%)
Hypersensitivity	1/543 (0.2%)
Infections and infestations
Anal abscess	2/543 (0.4%)
Appendicitis	1/543 (0.2%)
Cytomegalovirus viraemia	5/543 (0.9%)
Herpes virus infection	1/543 (0.2%)
Herpes zoster	6/543 (1.1%)
Infection	1/543 (0.2%)
Molluscum contagiosum	1/543 (0.2%)
Necrotising fasciitis	1/543 (0.2%)
Onychomycosis	1/543 (0.2%)
Oral herpes	1/543 (0.2%)
Orchitis	1/543 (0.2%)
Osteomyelitis	1/543 (0.2%)
Pneumonia	3/543 (0.6%)
Sinusitis	2/543 (0.4%)
Staphylococcal bacteraemia	1/543 (0.2%)
Tuberculosis	1/543 (0.2%)
Urinary tract infection	1/543 (0.2%)
Investigations
Alanine aminotransferase increased	2/543 (0.4%)
Aspartate aminotransferase increased	2/543 (0.4%)
Blood alkaline phosphatase	1/543 (0.2%)
Blood bilirubin increased	2/543 (0.4%)
Blood creatine increased	2/543 (0.4%)
Blood creatinine increased	4/543 (0.7%)
Blood test	1/543 (0.2%)
Blood urea increased	4/543 (0.7%)
Haemoglobin decreased	2/543 (0.4%)
Immunosuppressant drug level increased	1/543 (0.2%)
Liver function test abnormal	9/543 (1.7%)
Neutrophil count decreased	1/543 (0.2%)
Platelet count decreased	2/543 (0.4%)
Transaminases increased	5/543 (0.9%)
White blood cell count decreased	3/543 (0.6%)
White blood cell count increased	1/543 (0.2%)
Metabolism and nutrition disorders
Diabetes mellitus	1/543 (0.2%)
Hyperglycaemia	2/543 (0.4%)
Hyperkalaemia	2/543 (0.4%)
Hypernatraemia	1/543 (0.2%)
Hypomagnesaemia	1/543 (0.2%)
Hyponatraemia	1/543 (0.2%)
Hypophagia	1/543 (0.2%)
Musculoskeletal and connective tissue disorders
Arthralgia	1/543 (0.2%)
Muscular weakness	1/543 (0.2%)
Musculoskeletal pain	1/543 (0.2%)
Nervous system disorders
Ataxia	1/543 (0.2%)
Convulsion	2/543 (0.4%)
Dizziness	1/543 (0.2%)
Dysaesthesia	1/543 (0.2%)
Dysarthria	1/543 (0.2%)
Headache	2/543 (0.4%)
Neuropathy peripheral	1/543 (0.2%)
Peroneal nerve palsy	1/543 (0.2%)
Somnolence	1/543 (0.2%)
Tremor	1/543 (0.2%)
VIIth nerve paralysis	1/543 (0.2%)
Psychiatric disorders
Delirium	2/543 (0.4%)
Depression	1/543 (0.2%)
Disorientation	1/543 (0.2%)
Insomnia	6/543 (1.1%)
Major depression	1/543 (0.2%)
Renal and urinary disorders
Cystitis haemorrhagic	1/543 (0.2%)
Dysuria	1/543 (0.2%)
Haematuria	1/543 (0.2%)
Renal failure acute	2/543 (0.4%)
Reproductive system and breast disorders
Benign prostatic hyperplasia	1/543 (0.2%)
Respiratory, thoracic and mediastinal disorders
Cough	1/543 (0.2%)
Dyspnoea	7/543 (1.3%)
Haemoptysis	4/543 (0.7%)
Nasal congestion	1/543 (0.2%)
Oropharyngeal pain	1/543 (0.2%)
Pleural effusion	1/543 (0.2%)
Pulmonary oedema	1/543 (0.2%)
Skin and subcutaneous tissue disorders
Dermatitis	1/543 (0.2%)
Dermatitis contact	1/543 (0.2%)
Drug eruption	2/543 (0.4%)
Eczema asteatotic	1/543 (0.2%)
Ingrowing nail	1/543 (0.2%)
Palmar-plantar erythrodysaesthesia syndrome	1/543 (0.2%)
Petechiae	1/543 (0.2%)
Pruritus	5/543 (0.9%)
Rash	4/543 (0.7%)
Skin lesion	1/543 (0.2%)
Urticaria	2/543 (0.4%)
Vascular disorders
Haemorrhage	1/543 (0.2%)
Hypertension	2/543 (0.4%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.