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For tablets to be absorbed, the drug must dissolve after being swallowed. Drugs with low solubility sometimes require the inert ingredients in tablets to help the drug dissolve after being swallowed. This study uses itraconazole as an example drug with low solubility. Itraconazole tablets with different inert ingredients and manufacturing will be administered to healthy volunteers to see if the different inert ingredients and manufacturing impact drug absorption.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Sequence A (fast, medium, oral solution, then slow) | Experimental | Participants first receive fast tablet, then medium tablet, then oral solution, and then slow tablet. Washout period is (at least) one week. |
|
| Sequence B (medium, slow, fast, then oral solution) | Experimental | Participants first receive medium tablet, then slow tablet, then fast tablet, and then oral solution. Washout period is (at least) one week. |
|
| Sequence C (slow, oral solution, medium, then fast) | Experimental | 3, 4, 2, 1 Participants first receive slow tablet, then oral solution, then medium tablet, then fast tablet. Washout period is (at least) one week. |
|
| Sequence D (oral solution, fast, slow, then medium) | Experimental | Participants first receive oral solution, fast tablet, then slow tablet, and then medium tablet. Washout period is (at least) one week. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| fast itraconazole tablet | Drug | 100mg dose |
|
| Measure | Description | Time Frame |
|---|---|---|
| AUC | area under the curve from 0-72hr | 0-72hr |
| Measure | Description | Time Frame |
|---|---|---|
| Cmax | maximum concentration during the time interval | 0-72hr |
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Inclusion Criteria:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Maryland | Baltimore | Maryland | 21201 | United States |
Enrollment number is the number of participants who signed a consent form and passed screening tests.
Recruitment was done through flyers and A/V advertisement throughout the University of Maryland Baltimore campus. Additionally, ResearchMatch.org was used. Planned initial interactions were phone calls and emails from potential subjects. Additionally, individuals who previously indicated a willingness to be contacted for future studies were contacted. Recruitment period was from September 17th 2019 to June 24th 2021.
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| ID | Title | Description |
|---|---|---|
| FG000 | Sequence A (Fast, Medium, Oral Solution, Then Slow) | Participants first receive fast tablet, then medium tablet, then oral solution, and then slow tablet. Washout period is (at least) one week. fast itraconazole tablet: 100mg dose medium itraconazole tablet: 100mg dose slow itraconazole tablet: 100mg dose oral itraconazole solution: 100mg dose |
| FG001 | Sequence B (Medium, Slow, Fast, Then Oral Solution) | Participants first receive medium tablet, then slow tablet, then fast tablet, and then oral solution. Washout period is (at least) one week. fast itraconazole tablet: 100mg dose medium itraconazole tablet: 100mg dose slow itraconazole tablet: 100mg dose oral itraconazole solution: 100mg dose |
| FG002 | Sequence C (Slow, Oral Solution, Medium, Then Fast) | Participants first receive slow tablet, then oral solution, then medium tablet, then fast tablet. Washout period is (at least) one week. fast itraconazole tablet: 100mg dose medium itraconazole tablet: 100mg dose slow itraconazole tablet: 100mg dose oral itraconazole solution: 100mg dose |
| FG003 | Sequence D (Oral Solution, Fast, Slow, Then Medium) | Participants first receive oral solution, fast tablet, then slow tablet, and then medium tablet. Washout period is (at least) one week. fast itraconazole tablet: 100mg dose medium itraconazole tablet: 100mg dose slow itraconazole tablet: 100mg dose oral itraconazole solution: 100mg dose |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Sequence A (Fast, Medium, Oral Solution, Then Slow) | Participants first receive fast tablet, then medium tablet, then oral solution, and then slow tablet. Washout period is (at least) one week. fast itraconazole tablet: 100mg dose medium itraconazole tablet: 100mg dose slow itraconazole tablet: 100mg dose oral itraconazole solution: 100mg dose |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| 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 | AUC | area under the curve from 0-72hr | Seventeen participants were randomized in this cross-over study to receive all 4 itraconazole products at least one week apart. Twelve participants completed all 4 interventions. Analysis was only done of data from participants who completed all four interventions (n=12). | Posted | Mean | Standard Error | ng*hr/mL | 0-72hr |
|
Adverse event data were collected from the time enrollment (signed consent) to the last study visit (72-hr blood draw time point).
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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 | Fast Tablet | All participants who received Fast-release itraconazole 100 mg tablet, regardless if they finish the cross-over study |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Headache | Nervous system disorders | CTCAE Version 5.0 | Systematic Assessment | mild |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. James Polli | University of Maryland Baltimore | 410-706-8292 | jpolli@rx.umaryland.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Jun 11, 2019 | Sep 11, 2023 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D009181 | Mycoses |
| ID | Term |
|---|---|
| D001423 | Bacterial Infections and Mycoses |
| D007239 | Infections |
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|
| medium itraconazole tablet | Drug | 100mg dose |
|
|
| slow itraconazole tablet | Drug | 100mg dose |
|
|
| oral itraconazole solution | Drug | 100mg dose |
|
|
| Participant lived out of state and due to COVID-19 pandemic could not travel to study site. |
|
| BG001 |
| Sequence B (Medium, Slow, Fast, Then Oral Solution) |
Participants first receive medium tablet, then slow tablet, then fast tablet, and then oral solution. Washout period is (at least) one week. fast itraconazole tablet: 100mg dose medium itraconazole tablet: 100mg dose slow itraconazole tablet: 100mg dose oral itraconazole solution: 100mg dose |
| BG002 | Sequence C (Slow, Oral Solution, Medium, Then Fast) | Participants first receive slow tablet, then oral solution, then medium tablet, then fast tablet. Washout period is (at least) one week. fast itraconazole tablet: 100mg dose medium itraconazole tablet: 100mg dose slow itraconazole tablet: 100mg dose oral itraconazole solution: 100mg dose |
| BG003 | Sequence D (Oral Solution, Fast, Slow, Then Medium) | Participants first receive oral solution, fast tablet, then slow tablet, and then medium tablet. Washout period is (at least) one week. fast itraconazole tablet: 100mg dose medium itraconazole tablet: 100mg dose slow itraconazole tablet: 100mg dose oral itraconazole solution: 100mg dose |
| BG004 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Slow Tablet |
Slow-release itraconazole 100 mg tablet |
| OG003 | Oral Solution | Oral solution itraconazole 100 mg |
|
|
| Secondary | Cmax | maximum concentration during the time interval | Seventeen participants were randomized in this cross-over study to receive all 4 itraconazole products at least one week apart. Twelve participants completed all 4 interventions. Analysis was only done of data from participants who completed all four interventions. | Posted | Mean | Standard Error | ng/mL | 0-72hr |
|
|
|
| 0 |
| 14 |
| 0 |
| 14 |
| 3 |
| 14 |
| EG001 | Medium Tablet | All participants who received Medium-release itraconazole 100 mg tablet, regardless if they finish the cross-over study | 0 | 14 | 0 | 14 | 1 | 14 |
| EG002 | Slow Tablet | All participants who received Slow-release itraconazole 100 mg tablet, regardless if they finish the cross-over study | 0 | 13 | 0 | 13 | 1 | 13 |
| EG003 | Oral Solution | All participants who received Oral solution itraconazole 100 mg tablet, regardless if they finish the cross-over study | 0 | 12 | 0 | 12 | 1 | 12 |
| Fatigue | General disorders | CTCAE Version 5.0 | Systematic Assessment | mild |
|
| Abdominal pain | Gastrointestinal disorders | CTCAE Version 5.0 | Systematic Assessment | mild |
|
| Nausea/vomiting | Gastrointestinal disorders | CTCAE Version 5.0 | Systematic Assessment | mild |
|
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