Study to Test the Combination of Voriconazole and Anidulafungin in Patients Who Have, or Are Thought to Have, Invasive Aspergillosis and Who Are Unable to Take a Common Antifungal Therapy (Polyene)
Study Details
Study Description
Brief Summary
This study will test the effectiveness and the safety of giving two antifungal agents (voriconazole and anidulafungin) together to treat invasive aspergillosis in patients who are unable to tolerate polyene therapy.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 4 |
Detailed Description
The study was terminated on January 12, 2009 due to the overall low rate of enrollment. The decision to terminate the trial was not based on any safety concerns. Patients who were enrolled in the study prior to January 12, 2009 were allowed to remain in the study until completing their participation as specified in the protocol.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: combination 2 anidulafungin plus voriconazole |
Drug: voriconazole
Subjects with creatinine clearance at least 50 ml/min will receive initial treatment with IV (loading dose of 6 mg/kg Q12h followed by maintenance dose of 4 mg/kg Q12h) or oral (loading dose of 400 mg Q12h followed by maintenance dose of 300 mg Q12h). Subjects with creatinine clearance <50 ml/min will receive oral voriconazole (loading dose of 400 mg Q12h followed by maintenance dose of 300 mg Q12h).
Other Names:
|
| Experimental: combination 1 anidulafungin plus voriconazole |
Drug: anidulafungin
Loading dose of 200 mg QD followed by maintenance dose of 100 mg QD for up to a total of 28 days therapy
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Summary of Global Response at End of Treatment (EOT) [End of Treatment (Day 42)]
Number of subjects with global response consisting of a combination of clinical and radiological findings at the end of therapy. Possible outcome categories: Complete Response: resolution of all clinical signs and symptoms and more than 90% of lesions due to invasive aspergillosis that were visible on radiological studies; Partial Response: clinical improvement and greater than 50% improvement in radiological findings; Stable Response: no change from baseline or an improvement of less than 50% in radiological findings; Failure (no response): worsening disease.
Secondary Outcome Measures
- Summary of Global Response at Week 2, Week 4, and Week 6 [Week 2, Week 4, Week 6]
Number of subjects with global response consisting of a combination of clinical and radiological findings at the end of therapy. Possible outcome categories: Complete Response: resolution of all clinical signs and symptoms and more than 90% of lesions due to invasive aspergillosis that were visible on radiological studies; Partial Response: clinical improvement and greater than 50% improvement in radiological findings; Stable Response: no change from baseline or an improvement of less than 50% in radiological findings; Failure (no response): worsening disease.
- Summary of Mortality [Up to Week 6]
Number of subects with documented mortality (death).
- Galactomannan Titer Assay Levels and Global Response [Up to Week 6]
Number of subjects per Galactomannan titer level with global response for all subjects (with or without renal impairment). The galactomann assay is an immunological blood serum test used to diagnose invasive aspergillosis and to monitor disease progression. Global response is a composite of clinical and radiological findings summarized as Complete Response: resolution of all clinical signs and symptoms; Partial Response: clinical improvement; Stable Response: no change from baseline or an improvement of less than 50% in radiological findings; Failure (no response): worsening disease.
- Voriconazole Trough Levels With Intravenous and Oral Dosing [Week 1 through Week 6]
Voriconazole trough plasma concentrations measured as nanograms per milliliter (ng/mL).
Eligibility Criteria
Criteria
Inclusion Criteria:
Proven or probable invasive aspergillosis. Patient is intolerant to polyene therapy.
Exclusion Criteria:
Patients with invasive aspergillosis for more than 30 days at the time of study entry. Patients with uncontrolled bacterial or viral infection at the time of study entry. Patients with significant liver dysfunction or who are taking certain medications which interact with voriconazole.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Pfizer Investigational Site | Atlanta | Georgia | United States | 30322 |
| 2 | Pfizer Investigational Site | Detroit | Michigan | United States | 48202 |
| 3 | Pfizer Investigational Site | Fort Worth | Texas | United States | 76104 |
| 4 | Pfizer Investigational Site | Fort Worth | Texas | United States | 76107 |
Sponsors and Collaborators
- Pfizer
Investigators
- Study Director: Pfizer CT.gov Call Center, Pfizer
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.- A8851014
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail | Study was closed due to an overall low rate of enrollment after only 6 subjects enrolled. |
| Arm/Group Title | Anidulalfungin and Voriconazole |
|---|---|
| Arm/Group Description | Voriconazole: subjects with creatinine clearance at least 50 milliliters per minute (ml/min) will receive initial treatment with intravenous (IV) (loading dose of 6 milligrams per kilogram [mg/kg] every 12 hours [Q12h]) followed by maintenance dose of 4 mg/kg Q12h or oral (PO) (loading dose of 400 mg Q12h followed by maintenance dose of 300 mg Q12h). Subjects with creatinine clearance <50 ml/min will receive oral Voriconazole (loading dose of 400 mg Q12h followed by maintenance dose of 300 mg Q12h). Anidulafungin: loading dose of 200 mg once daily (QD) followed by maintenance dose of 100 mg QD for up to a total of 28 days therapy. Subjects remain on combination therapy for minimum of 14 days and a maximum of 28 days; after combination therapy complete, subjects may remain on a maintenance dose of Voriconazole monotherapy until Day 42. |
| Period Title: Overall Study | |
| STARTED | 6 |
| COMPLETED | 5 |
| NOT COMPLETED | 1 |
Baseline Characteristics
| Arm/Group Title | Anidulalfungin and Voriconazole |
|---|---|
| Arm/Group Description | Voriconazole: subjects with creatinine clearance at least 50 milliliters per minute (ml/min) will receive initial treatment with intravenous (IV) (loading dose of 6 milligrams per kilogram [mg/kg] every 12 hours [Q12h]) followed by maintenance dose of 4 mg/kg Q12h or oral (PO) (loading dose of 400 mg Q12h followed by maintenance dose of 300 mg Q12h). Subjects with creatinine clearance <50 ml/min will receive oral Voriconazole (loading dose of 400 mg Q12h followed by maintenance dose of 300 mg Q12h). Anidulafungin: loading dose of 200 mg once daily (QD) followed by maintenance dose of 100 mg QD for up to a total of 28 days therapy. Subjects remain on combination therapy for minimum of 14 days and a maximum of 28 days; after combination therapy complete, subjects may remain on a maintenance dose of Voriconazole monotherapy until Day 42. |
| Overall Participants | 6 |
| Age, Customized (participants) [Number] | |
| Between 57 and 83 years |
6
100%
|
| Sex: Female, Male (Count of Participants) | |
| Female |
1
16.7%
|
| Male |
5
83.3%
|
Outcome Measures
| Title | Summary of Global Response at End of Treatment (EOT) |
|---|---|
| Description | Number of subjects with global response consisting of a combination of clinical and radiological findings at the end of therapy. Possible outcome categories: Complete Response: resolution of all clinical signs and symptoms and more than 90% of lesions due to invasive aspergillosis that were visible on radiological studies; Partial Response: clinical improvement and greater than 50% improvement in radiological findings; Stable Response: no change from baseline or an improvement of less than 50% in radiological findings; Failure (no response): worsening disease. |
| Time Frame | End of Treatment (Day 42) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-treat (ITT): includes all subjects who received at least 1 dose of study medication. No descriptive or inferential analysis was completed due to low enrollment and subsequent early termination of study. |
| Arm/Group Title | Anidulalfungin and Voriconazole |
|---|---|
| Arm/Group Description | Anidulafungin and voriconazole in combination followed by monotherapy. |
| Measure Participants | 6 |
| Failure (No response) |
1
16.7%
|
| Partial response |
3
50%
|
| Stable response |
0
0%
|
| Complete response |
2
33.3%
|
| Title | Summary of Global Response at Week 2, Week 4, and Week 6 |
|---|---|
| Description | Number of subjects with global response consisting of a combination of clinical and radiological findings at the end of therapy. Possible outcome categories: Complete Response: resolution of all clinical signs and symptoms and more than 90% of lesions due to invasive aspergillosis that were visible on radiological studies; Partial Response: clinical improvement and greater than 50% improvement in radiological findings; Stable Response: no change from baseline or an improvement of less than 50% in radiological findings; Failure (no response): worsening disease. |
| Time Frame | Week 2, Week 4, Week 6 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT; due to low study enrollment, data not summarized by global response at Week 2, Week 4, and Week 6. Cross-reference outcome measure: Summary of Global Response at End of Treatment (EOT). |
| Arm/Group Title | Anidulalfungin and Voriconazole |
|---|---|
| Arm/Group Description | Anidulafungin and voriconazole in combination followed by monotherapy. |
| Measure Participants | 0 |
| Title | Summary of Mortality |
|---|---|
| Description | Number of subects with documented mortality (death). |
| Time Frame | Up to Week 6 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT |
| Arm/Group Title | Anidulalfungin and Voriconazole |
|---|---|
| Arm/Group Description | Anidulafungin and voriconazole in combination followed by monotherapy. |
| Measure Participants | 6 |
| Number [participants] |
1
16.7%
|
| Title | Galactomannan Titer Assay Levels and Global Response |
|---|---|
| Description | Number of subjects per Galactomannan titer level with global response for all subjects (with or without renal impairment). The galactomann assay is an immunological blood serum test used to diagnose invasive aspergillosis and to monitor disease progression. Global response is a composite of clinical and radiological findings summarized as Complete Response: resolution of all clinical signs and symptoms; Partial Response: clinical improvement; Stable Response: no change from baseline or an improvement of less than 50% in radiological findings; Failure (no response): worsening disease. |
| Time Frame | Up to Week 6 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT. No descriptive or inferential analysis was completed due to low enrollment and subsequent early termination of study. |
| Arm/Group Title | Anidulalfungin and Voriconazole |
|---|---|
| Arm/Group Description | Anidulafungin and voriconazole in combination followed by monotherapy. |
| Measure Participants | 0 |
| Title | Voriconazole Trough Levels With Intravenous and Oral Dosing |
|---|---|
| Description | Voriconazole trough plasma concentrations measured as nanograms per milliliter (ng/mL). |
| Time Frame | Week 1 through Week 6 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT; only 1 pharmacokinetic sample was collected for each subject, therefore a comprehensive analysis of trough plasma concentrations was not completed due to insufficient data. |
| Arm/Group Title | Anidulalfungin and Voriconazole |
|---|---|
| Arm/Group Description | Anidulafungin and voriconazole in combination followed by monotherapy. |
| Measure Participants | 0 |
Adverse Events
| Time Frame | ||
|---|---|---|
| Adverse Event Reporting Description | ||
| Arm/Group Title | Anidulalfungin and Voriconazole | |
| Arm/Group Description | Voriconazole: subjects with creatinine clearance at least 50 milliliters per minute (ml/min) will receive initial treatment with intravenous (IV) (loading dose of 6 milligrams per kilogram [mg/kg] every 12 hours [Q12h]) followed by maintenance dose of 4 mg/kg Q12h or oral (PO) (loading dose of 400 mg Q12h followed by maintenance dose of 300 mg Q12h). Subjects with creatinine clearance <50 ml/min will receive oral Voriconazole (loading dose of 400 mg Q12h followed by maintenance dose of 300 mg Q12h). Anidulafungin: loading dose of 200 mg once daily (QD) followed by maintenance dose of 100 mg QD for up to a total of 28 days therapy. Subjects remain on combination therapy for minimum of 14 days and a maximum of 28 days; after combination therapy complete, subjects may remain on a maintenance dose of Voriconazole monotherapy until Day 42. | |
All Cause Mortality |
||
| Anidulalfungin and Voriconazole | ||
| Affected / at Risk (%) | # Events | |
| Total | / (NaN) | |
Serious Adverse Events |
||
| Anidulalfungin and Voriconazole | ||
| Affected / at Risk (%) | # Events | |
| Total | 4/6 (66.7%) | |
| General disorders | ||
| Disease progression | 1/6 (16.7%) | |
| Renal and urinary disorders | ||
| Renal failure acute | 1/6 (16.7%) | |
| Respiratory, thoracic and mediastinal disorders | ||
| Hydropneumothorax | 1/6 (16.7%) | |
| Pulmonary embolism | 1/6 (16.7%) | |
| Respiratory failure | 1/6 (16.7%) | |
Other (Not Including Serious) Adverse Events |
||
| Anidulalfungin and Voriconazole | ||
| Affected / at Risk (%) | # Events | |
| Total | 6/6 (100%) | |
| Blood and lymphatic system disorders | ||
| Anaemia | 1/6 (16.7%) | |
| Leukocytosis | 1/6 (16.7%) | |
| Cardiac disorders | ||
| Cardiac failure congestive | 2/6 (33.3%) | |
| Gastrointestinal disorders | ||
| Diarrhoea | 1/6 (16.7%) | |
| Haematemesis | 1/6 (16.7%) | |
| Nausea | 1/6 (16.7%) | |
| Vomiting | 2/6 (33.3%) | |
| General disorders | ||
| Pyrexia | 1/6 (16.7%) | |
| Infections and infestations | ||
| Oropharyngeal candidiasis | 1/6 (16.7%) | |
| Investigations | ||
| Blood glucose increased | 1/6 (16.7%) | |
| Blood magnesium decreased | 1/6 (16.7%) | |
| Blood potassium increased | 1/6 (16.7%) | |
| Metabolism and nutrition disorders | ||
| Acidosis | 1/6 (16.7%) | |
| Hyperphosphataemia | 1/6 (16.7%) | |
| Hypocalcaemia | 1/6 (16.7%) | |
| Hypoglycaemia | 1/6 (16.7%) | |
| Hypophosphataemia | 1/6 (16.7%) | |
| Metabolic alkalosis | 1/6 (16.7%) | |
| Psychiatric disorders | ||
| Anxiety | 1/6 (16.7%) | |
| Mental status changes | 1/6 (16.7%) | |
| Skin and subcutaneous tissue disorders | ||
| Decubitus ulcer | 1/6 (16.7%) | |
| Subcutaneous emphysema | 1/6 (16.7%) | |
| Vascular disorders | ||
| Deep vein thrombosis | 1/6 (16.7%) | |
| Subclavian vein thrombosis | 1/6 (16.7%) | |
| Venous thrombosis limb | 1/6 (16.7%) | |
Limitations/Caveats
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 < 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), < 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
Results Point of Contact
| Name/Title | Pfizer ClinicalTrials.gov Call Center |
|---|---|
| Organization | Pfizer, Inc. |
| Phone | 1-800-718-1021 |
| ClinicalTrials.govCallCenter@pfizer.com |
- A8851014