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| ID | Type | Description | Link |
|---|---|---|---|
| 2012-003140-68 | EudraCT Number |
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Study terminated due to an unfavorable risk-benefit analysis
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This single site study will examine plasma and alveolar compartment (AC) levels of posaconazole in cystic fibrosis (CF) and non-cystic fibrosis (non-CF) lung transplant recipients receiving routine post-operative anti-fungal prophylaxis. Invasive fungal infection rates will be assessed following transplantation.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Posaconazole - CF Participants | Experimental | Posaconazole 400 mg oral solution twice daily administered with Calogen® to optimize absorption for a total of 6 weeks starting within 12 hours of leaving surgery, thereafter administered in the hospital or as an outpatient; the dose could be changed to posaconazole 200 mg 4 times per day if the participant is unable to meet the conditions for optimal absorption of posaconazole. |
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| Posaconazole - Non-CF Participants | Experimental | Posaconazole 400 mg oral solution twice daily administered with Calogen® to optimize absorption for a total of 6 weeks starting within 12 hours of leaving surgery, thereafter administered in the hospital or as an outpatient; the dose could be changed to posaconazole 200 mg 4 times per day if the participant is unable to meet the conditions for optimal absorption of posaconazole. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Posaconazole | Drug |
|
|
| Measure | Description | Time Frame |
|---|---|---|
| Time to Reach 90% of the Steady State Serum Concentration of Posaconazole | Blood samples for measurement of serum posaconazole were collected approximately 4 hours after the first daily dose on Days 1-12 and every Monday and Thursday on Days 13-43. The time to reach 90% of the steady state serum posaconazole concentration was to be estimated from fitting a linear model to the concentration data over time. The data did not permit estimation of the endpoint from the modeling proposed in the protocol. | Four hours after the first daily dose on Days 1-12 and every Monday and Thursday on Days 13-43 |
| Concentration of Posaconazole in Bronchoalveolar Lavage (BAL) and Serum | Concurrent BAL and serum samples for measurement of posaconazole concentration were to be collected during any clinically-indicated bronchoscopy. A participant could have more than 1 bronchoscopy. | Up to Day 42 |
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Participants Who Develop Invasive Fungal Infection | Invasive fungal infection was assessed using the Mycoses Study Group/European Organisation for Research and Treatment of Cancer (MSG/EORTC) criteria. Infections counted in the analysis were those classified as 'proven', 'probable', or 'possible' according to the criteria. | Up to Day 84 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Medical Director | Merck Sharp & Dohme LLC | Study Director |
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| ID | Type | URL | Comment |
|---|---|---|---|
| CSR Synopsis | View IPD |
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| ID | Title | Description |
|---|---|---|
| FG000 | Cystic Fibrosis Participants | Cystic fibrosis participants received posaconazole 400 mg oral solution twice daily administered with Calogen® to optimize absorption for a total of 6 weeks starting within 12 hours of leaving surgery, thereafter administered in the hospital or as an outpatient; the dose could be changed to posaconazole 200 mg 4 times per day if the participant is unable to meet the conditions for optimal absorption of posaconazole. |
| FG001 | Non-Cystic Fibrosis Participants | Non-cystic fibrosis participants received posaconazole 400 mg oral solution twice daily administered with Calogen® to optimize absorption for a total of 6 weeks starting within 12 hours of leaving surgery, thereafter administered in the hospital or as an outpatient; the dose could be changed to posaconazole 200 mg 4 times per day if the participant is unable to meet the conditions for optimal absorption of posaconazole. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Cystic Fibrosis Participants | Cystic fibrosis participants received posaconazole 400 mg oral solution twice daily administered with Calogen® to optimize absorption for a total of 6 weeks starting within 12 hours of leaving surgery, thereafter administered in the hospital or as an outpatient; the dose could be changed to posaconazole 200 mg 4 times per day if the participant is unable to meet the conditions for optimal absorption of posaconazole. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Time to Reach 90% of the Steady State Serum Concentration of Posaconazole | Blood samples for measurement of serum posaconazole were collected approximately 4 hours after the first daily dose on Days 1-12 and every Monday and Thursday on Days 13-43. The time to reach 90% of the steady state serum posaconazole concentration was to be estimated from fitting a linear model to the concentration data over time. The data did not permit estimation of the endpoint from the modeling proposed in the protocol. | The population to be analyzed included participants who complied with the protocol sufficiently to ensure that the results would exhibit the effects of treatment | Posted | Four hours after the first daily dose on Days 1-12 and every Monday and Thursday on Days 13-43 |
|
Up to Day 88
All enrolled participants were assessed for adverse events. Adverse events that were serious and/or related to study drug were collected in the study. Related adverse events were those classified as possibly, probably, or certainly related to study drug.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Cystic Fibrosis Participants | Cystic fibrosis participants received posaconazole 400 mg oral solution twice daily administered with Calogen® to optimize absorption for a total of 6 weeks starting within 12 hours of leaving surgery, thereafter administered in the hospital or as an outpatient; the dose could be changed to posaconazole 200 mg 4 times per day if the participant is unable to meet the conditions for optimal absorption of posaconazole. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Neutropenia | Blood and lymphatic system disorders | MedDRA version 15.1 | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Nausea | Gastrointestinal disorders | MedDRA version 15.1 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Senior Vice President, Global Clinical Development | Merck Sharp & Dohme Corp. | 1-800-672-6372 | ClinicalTrialsDisclosure@merck.com |
| ID | Term |
|---|---|
| D009181 | Mycoses |
| ID | Term |
|---|---|
| D001423 | Bacterial Infections and Mycoses |
| D007239 | Infections |
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| ID | Term |
|---|---|
| C101425 | posaconazole |
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| Calogen® | Drug |
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| Protocol Violation |
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| Lack of Efficacy |
|
| BG001 | Non-Cystic Fibrosis Participants | Non-cystic fibrosis participants received posaconazole 400 mg oral solution twice daily administered with Calogen® to optimize absorption for a total of 6 weeks starting within 12 hours of leaving surgery, thereafter administered in the hospital or as an outpatient; the dose could be changed to posaconazole 200 mg 4 times per day if the participant is unable to meet the conditions for optimal absorption of posaconazole. |
| BG002 | Total | Total of all reporting groups |
| Years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| OG001 | Non-Cystic Fibrosis Participants | Non-cystic fibrosis participants received posaconazole 400 mg oral solution twice daily administered with Calogen® to optimize absorption for a total of 6 weeks starting within 12 hours of leaving surgery, thereafter administered in the hospital or as an outpatient; the dose could be changed to posaconazole 200 mg 4 times per day if the participant is unable to meet the conditions for optimal absorption of posaconazole. |
|
| Post-Hoc | Time to Reach a Serum Concentration of Posaconazole of >=0.5 mg/L | Blood samples for measurement of serum posaconazole were collected approximately 4 hours after the first daily dose on Days 1-12 and every Monday and Thursday on Days 13-43. A posaconazole concentration >=0.5 mg/L is the therapeutic level, the concentration thought to lead to antifungal efficacy. The time at which the serum posaconazole concentration reached >=0.5 mg/mL and remained at that level for all subsequent assessments was recorded. | The population analyzed included all enrolled participants who reached and maintained posaconazole concentration of >=0.5 mg/L | Posted | Mean | Standard Deviation | Days | Four hours after the first daily dose on Days 1-12 and every Monday and Thursday on Days 13-43 |
|
|
|
| Post-Hoc | Maximum Serum Concentration of Posaconazole (Cmax) | Blood samples for measurement of serum posaconazole were collected approximately 4 hours after the first daily dose on Days 1-12 and every Monday and Thursday on Days 13-43. The maximum serum concentration of posaconazole was recorded. | The population analyzed included all enrolled participants | Posted | Mean | Standard Deviation | mg/L | Four hours after the first daily dose on Days 1-12 and every Monday and Thursday on Days 13-43 |
|
|
|
| Post-Hoc | Time to Maximum Serum Concentration of Posaconazole (Tmax) | Blood samples for measurement of serum posaconazole were collected approximately 4 hours after the first daily dose on Days 1-12 and every Monday and Thursday on Days 13-43. The time required to achieve the maximum serum concentration of posaconazole was recorded. | The population analyzed included all enrolled participants | Posted | Mean | Standard Deviation | Days | Four hours after the first daily dose on Days 1-12 and every Monday and Thursday on Days 13-43 |
|
|
|
| Primary | Concentration of Posaconazole in Bronchoalveolar Lavage (BAL) and Serum | Concurrent BAL and serum samples for measurement of posaconazole concentration were to be collected during any clinically-indicated bronchoscopy. A participant could have more than 1 bronchoscopy. | The population analyzed included all enrolled participants who had BAL and serum samples collected at the time of bronchoscopy and analyzed for posaconazole concentration. A participant could have more than 1 pair of samples (BAL and serum) included in the analysis. | Posted | Mean | Standard Deviation | mg/L | Up to Day 42 | paired BAL and serum samples | paired BAL and serum samples |
|
|
|
|
| Secondary | Percentage of Participants Who Develop Invasive Fungal Infection | Invasive fungal infection was assessed using the Mycoses Study Group/European Organisation for Research and Treatment of Cancer (MSG/EORTC) criteria. Infections counted in the analysis were those classified as 'proven', 'probable', or 'possible' according to the criteria. | Participants were analyzed according to the group in which they were enrolled | Posted | Number | 95% Confidence Interval | Percentage of participants | Up to Day 84 |
|
|
|
| 6 |
| 8 |
| 1 |
| 8 |
| EG001 | Non-Cystic Fibrosis Participants | Non-cystic fibrosis participants received posaconazole 400 mg oral solution twice daily administered with Calogen® to optimize absorption for a total of 6 weeks starting within 12 hours of leaving surgery, thereafter administered in the hospital or as an outpatient; the dose could be changed to posaconazole 200 mg 4 times per day if the participant is unable to meet the conditions for optimal absorption of posaconazole. | 10 | 18 | 2 | 18 |
| Supraventricular tachycardia | Cardiac disorders | MedDRA version 15.1 | Systematic Assessment |
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| Systemic inflammatory response syndrome | General disorders | MedDRA version 15.1 | Systematic Assessment |
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| Liver injury | Hepatobiliary disorders | MedDRA version 15.1 | Systematic Assessment |
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| Immunosuppressant drug level decreased | Investigations | MedDRA version 15.1 | Systematic Assessment |
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| Renal failure | Renal and urinary disorders | MedDRA version 15.1 | Systematic Assessment |
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| Acute respiratory failure | Respiratory, thoracic and mediastinal disorders | MedDRA version 15.1 | Systematic Assessment |
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| Hepatic function abnormal | Hepatobiliary disorders | MedDRA version 15.1 | Systematic Assessment |
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| Transplant rejection | Immune system disorders | MedDRA version 15.1 | Systematic Assessment |
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| Fungal infection | Infections and infestations | MedDRA version 15.1 | Systematic Assessment |
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| Lower respiratory tract infection | Infections and infestations | MedDRA version 15.1 | Systematic Assessment |
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| Pneumonia | Infections and infestations | MedDRA version 15.1 | Systematic Assessment |
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| Cerebral infarction | Nervous system disorders | MedDRA version 15.1 | Systematic Assessment |
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| Renal failure acute | Renal and urinary disorders | MedDRA version 15.1 | Systematic Assessment |
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| Vision blurred | Eye disorders | MedDRA version 15.1 | Systematic Assessment |
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| Alanine aminotransferase increased | Investigations | MedDRA version 15.1 | Systematic Assessment |
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| Immunosuppressant drug level increased | Investigations | MedDRA version 15.1 | Systematic Assessment |
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| Renal failure | Renal and urinary disorders | MedDRA version 15.1 | Systematic Assessment |
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| Renal failure acute | Renal and urinary disorders | MedDRA version 15.1 | Systematic Assessment |
|
The investigator agrees to provide to the sponsor 45 days prior to submission for publication or presentation, review copies of abstracts or manuscripts for publication that report any results of the trial. The sponsor shall have the right to review and comment with respect to publications, abstracts, slides, and manuscripts and the right to review and comment on the data analysis and presentation.
| Spearman rank correlation |
| 0.057 |
| Spearman rank correlation coefficient |
| 0.59 |
| Superiority or Other |