Not provided
Not provided
Not provided
Not provided
Not provided
Recruitment challenges and lack of funding caused an early end to this study
Not provided
Not provided
Not provided
Not provided
| Name | Class |
|---|---|
| FDA Office of Orphan Products Development | FED |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
The purpose of this study is to determine if nikkomycin Z is safe when administered at different dose levels for 14 days. The study will also determine blood levels and urinary excretion of nikkomycin Z in relation to dose administered. Patients with mild forms of Valley Fever pneumonia will be eligible to participate and will be allocated to receive treatment with nikkomycin Z (various doses) or a placebo. A secondary goal of this study is to evaluate the effectiveness and dose response of nikkomycin Z in an exploratory analysis.
Every year there are 50,000 new U.S. cases of coccidioidomycosis (Valley Fever). The majority of these illnesses occur as a result of endemic exposure in Arizona and California. The benefits of antifungal therapy for uncomplicated disease are not currently established. Current therapies for serious and complicated forms of coccidioidomycosis are only partially effective and in themselves are unable to eradicate the fungus from sites of infection, commonly resulting in breakthrough infection and/or relapse. Nikkomycin Z is effective in the mouse model and results in improved microbiological response over fluconazole.
The goals of this study include: 1) Evaluating the safety and tolerance of nikkomycin Z following administration of multiple doses (50 mg Q 12 h to 750 mg Q 8 h) for two week and 2) Evaluating the pharmacokinetics of nikkomycin Z after single and multiple doses in relationship to dose. The study will include patients with uncomplicated Coccidioides pneumonia (mild illness) which will allow exploratory analysis of efficacy and dose response based on biomarkers.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| A - First dose level (n=5) | Experimental | nikkomycin Z 50 mg BID x 14 days |
|
| B - Second Dose Level (n=10) | Experimental | nikkomycin Z nikkomycin Z 250 mg BID x 14 days |
|
| C - Third Dose Level (n=10) | Experimental | nikkomycin Z 500 mg BID x 14 days |
|
| D - Fourth Dose Level (n=5) | Experimental | nikkomycin Z 750 BID x 14 days |
|
| Placebo | Placebo Comparator | placebo BID x 14 days |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| nikkomycin Z | Drug | Stage I: Multiple rising doses. Doses packaged on a unit dose basis in 50 and 250 mg capsules. Subjects take 1-3 capsules per dosing block for 14 days unless ADE or study withdrawal. Dose escalation unless a dose-limiting adverse effect is noted. Subjects assigned to BID dosing will receive 28 doses and subjects assigned to TID dosing will receive 42 doses.
At least 4 subjects complete lower dose before randomization includes next higher dose. Stage II will be a single dose level selected based on pharmacodynamics and safety from Stage I for 20 additional subjects using 4:1 randomization. |
| Measure | Description | Time Frame |
|---|---|---|
| Concentration of Nikkomycin Z in the Blood Over Time (AUC) | 0, 0.25, 0.5, 0.75, 1.0, 1.5, 2 , 3, 4, 6, 8 and 12 h hours post-dose on Day 1 and Day 14 | |
| Highest Concentration of Nikkomycin Z in the Blood (Cmax) | 0, 0.25, 0.5, 0.75, 1.0, 1.5, 2 , 3, 4, 6, 8 and 12 h hours post-dose on Day 1 and Day 14 |
Not provided
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| David E Nix, Pharm D | University of Arizona | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Clinical & Translational Research Center - University of Arizona | Tucson | Arizona | 85721 | United States |
Not provided
| Label | URL |
|---|---|
| The Valley Fever Center for Excellence | View source |
Not provided
De-identified data may be shared for legitimate use to further nikkomycin Z development.
Study was terminated due to poor enrollment. Study report was not generated beyond safety data.
Contact Valley fever Solutions - current license for development.
Not provided
Not provided
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | A - First Dose Level | nikkomycin Z 50 mg BID x 14 days nikkomycin Z: Stage I: Multiple rising doses. Doses packaged on a unit dose basis in 50 and 250 mg capsules. Subjects take 1-3 capsules per dosing block for 14 days unless ADE or study withdrawal. Dose escalation unless a dose-limiting adverse effect is noted. Subjects assigned to BID dosing will receive 28 doses and subjects assigned to TID dosing will receive 42 doses.
At least 4 subjects complete lower dose before randomization includes next higher dose. Stage II will be a single dose level selected based on pharmacodynamics and safety from Stage I for 20 additional subjects using 4:1 randomization. |
| FG001 | B - Second Dose Level | nikkomycin Z nikkomycin Z 250 mg BID x 14 days nikkomycin Z: Stage I: Multiple rising doses. Doses packaged on a unit dose basis in 50 and 250 mg capsules. Subjects take 1-3 capsules per dosing block for 14 days unless ADE or study withdrawal. Dose escalation unless a dose-limiting adverse effect is noted. Subjects assigned to BID dosing will receive 28 doses and subjects assigned to TID dosing will receive 42 doses.
At least 4 subjects complete lower dose before randomization includes next higher dose. Stage II will be a single dose level selected based on pharmacodynamics and safety from Stage I for 20 additional subjects using 4:1 randomization. |
| FG002 | C - Third Dose Level | nikkomycin Z 500 mg BID x 14 days nikkomycin Z: Stage I: Multiple rising doses. Doses packaged on a unit dose basis in 50 and 250 mg capsules. Subjects take 1-3 capsules per dosing block for 14 days unless ADE or study withdrawal. Dose escalation unless a dose-limiting adverse effect is noted. Subjects assigned to BID dosing will receive 28 doses and subjects assigned to TID dosing will receive 42 doses.
At least 4 subjects complete lower dose before randomization includes next higher dose. Stage II will be a single dose level selected based on pharmacodynamics and safety from Stage I for 20 additional subjects using 4:1 randomization. |
| FG003 | D - Fourth Dose Level | nikkomycin Z 750 BID x 14 days nikkomycin Z: Stage I: Multiple rising doses. Doses packaged on a unit dose basis in 50 and 250 mg capsules. Subjects take 1-3 capsules per dosing block for 14 days unless ADE or study withdrawal. Dose escalation unless a dose-limiting adverse effect is noted. Subjects assigned to BID dosing will receive 28 doses and subjects assigned to TID dosing will receive 42 doses.
At least 4 subjects complete lower dose before randomization includes next higher dose. Stage II will be a single dose level selected based on pharmacodynamics and safety from Stage I for 20 additional subjects using 4:1 randomization. |
| FG004 | Placebo | placebo BID x 14 days Placebo: Placebo comparator |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | A - First Dose Level (n=5) | nikkomycin Z 50 mg BID x 14 days nikkomycin Z: Stage I: Multiple rising doses. Doses packaged on a unit dose basis in 50 and 250 mg capsules. Subjects take 1-3 capsules per dosing block for 14 days unless ADE or study withdrawal. Dose escalation unless a dose-limiting adverse effect is noted. Subjects assigned to BID dosing will receive 28 doses and subjects assigned to TID dosing will receive 42 doses.
At least 4 subjects complete lower dose before randomization includes next higher dose. Stage II will be a single dose level selected based on pharmacodynamics and safety from Stage I for 20 additional subjects using 4:1 randomization. |
| 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 | Concentration of Nikkomycin Z in the Blood Over Time (AUC) | The study was terminated after enrollment of 6 subjects | Posted | Mean | Standard Deviation | mg*hr/L | 0, 0.25, 0.5, 0.75, 1.0, 1.5, 2 , 3, 4, 6, 8 and 12 h hours post-dose on Day 1 and Day 14 |
|
Not provided
Not provided
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | A - First Dose Level (n=5) | nikkomycin Z 50 mg BID x 14 days nikkomycin Z: Stage I: Multiple rising doses. Doses packaged on a unit dose basis in 50 and 250 mg capsules. Subjects take 1-3 capsules per dosing block for 14 days unless ADE or study withdrawal. Dose escalation unless a dose-limiting adverse effect is noted. Subjects assigned to BID dosing will receive 28 doses and subjects assigned to TID dosing will receive 42 doses.
At least 4 subjects complete lower dose before randomization includes next higher dose. Stage II will be a single dose level selected based on pharmacodynamics and safety from Stage I for 20 additional subjects using 4:1 randomization. |
Not provided
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Hypotension | Vascular disorders | Systematic Assessment |
Early termination leading to small numbers of subjects analyzed
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. John Galgiani | University of Arizona | (520) 626-4968 | spherule@email.arizona.edu |
Not provided
| ID | Term |
|---|---|
| D003047 | Coccidioidomycosis |
| ID | Term |
|---|---|
| D009181 | Mycoses |
| D001423 | Bacterial Infections and Mycoses |
| D007239 | Infections |
Not provided
Not provided
| ID | Term |
|---|---|
| C011952 | nikkomycin |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
|
| Placebo | Drug | Placebo comparator |
|
| BG001 | B - Second Dose Level (n=10) | nikkomycin Z nikkomycin Z 250 mg BID x 14 days nikkomycin Z: Stage I: Multiple rising doses. Doses packaged on a unit dose basis in 50 and 250 mg capsules. Subjects take 1-3 capsules per dosing block for 14 days unless ADE or study withdrawal. Dose escalation unless a dose-limiting adverse effect is noted. Subjects assigned to BID dosing will receive 28 doses and subjects assigned to TID dosing will receive 42 doses.
At least 4 subjects complete lower dose before randomization includes next higher dose. Stage II will be a single dose level selected based on pharmacodynamics and safety from Stage I for 20 additional subjects using 4:1 randomization. |
| BG002 | C - Third Dose Level (n=10) | nikkomycin Z 500 mg BID x 14 days nikkomycin Z: Stage I: Multiple rising doses. Doses packaged on a unit dose basis in 50 and 250 mg capsules. Subjects take 1-3 capsules per dosing block for 14 days unless ADE or study withdrawal. Dose escalation unless a dose-limiting adverse effect is noted. Subjects assigned to BID dosing will receive 28 doses and subjects assigned to TID dosing will receive 42 doses.
At least 4 subjects complete lower dose before randomization includes next higher dose. Stage II will be a single dose level selected based on pharmacodynamics and safety from Stage I for 20 additional subjects using 4:1 randomization. |
| BG003 | D - Fourth Dose Level (n=5) | nikkomycin Z 750 BID x 14 days nikkomycin Z: Stage I: Multiple rising doses. Doses packaged on a unit dose basis in 50 and 250 mg capsules. Subjects take 1-3 capsules per dosing block for 14 days unless ADE or study withdrawal. Dose escalation unless a dose-limiting adverse effect is noted. Subjects assigned to BID dosing will receive 28 doses and subjects assigned to TID dosing will receive 42 doses.
At least 4 subjects complete lower dose before randomization includes next higher dose. Stage II will be a single dose level selected based on pharmacodynamics and safety from Stage I for 20 additional subjects using 4:1 randomization. |
| BG004 | Placebo | placebo BID x 14 days Placebo: Placebo comparator |
| BG005 | Total | Total of all reporting groups |
| Participants |
|
| 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 |
|
| OG001 | B - Second Dose Level (n=10) | nikkomycin Z nikkomycin Z 250 mg BID x 14 days nikkomycin Z: Stage I: Multiple rising doses. Doses packaged on a unit dose basis in 50 and 250 mg capsules. Subjects take 1-3 capsules per dosing block for 14 days unless ADE or study withdrawal. Dose escalation unless a dose-limiting adverse effect is noted. Subjects assigned to BID dosing will receive 28 doses and subjects assigned to TID dosing will receive 42 doses.
At least 4 subjects complete lower dose before randomization includes next higher dose. Stage II will be a single dose level selected based on pharmacodynamics and safety from Stage I for 20 additional subjects using 4:1 randomization. |
| OG002 | C - Third Dose Level (n=10) | nikkomycin Z 500 mg BID x 14 days nikkomycin Z: Stage I: Multiple rising doses. Doses packaged on a unit dose basis in 50 and 250 mg capsules. Subjects take 1-3 capsules per dosing block for 14 days unless ADE or study withdrawal. Dose escalation unless a dose-limiting adverse effect is noted. Subjects assigned to BID dosing will receive 28 doses and subjects assigned to TID dosing will receive 42 doses.
At least 4 subjects complete lower dose before randomization includes next higher dose. Stage II will be a single dose level selected based on pharmacodynamics and safety from Stage I for 20 additional subjects using 4:1 randomization. |
| OG003 | D - Fourth Dose Level (n=5) | nikkomycin Z 750 BID x 14 days nikkomycin Z: Stage I: Multiple rising doses. Doses packaged on a unit dose basis in 50 and 250 mg capsules. Subjects take 1-3 capsules per dosing block for 14 days unless ADE or study withdrawal. Dose escalation unless a dose-limiting adverse effect is noted. Subjects assigned to BID dosing will receive 28 doses and subjects assigned to TID dosing will receive 42 doses.
At least 4 subjects complete lower dose before randomization includes next higher dose. Stage II will be a single dose level selected based on pharmacodynamics and safety from Stage I for 20 additional subjects using 4:1 randomization. |
|
|
| Primary | Highest Concentration of Nikkomycin Z in the Blood (Cmax) | The study was terminated after enrollment of 6 subjects | Posted | Mean | Standard Deviation | mg/L | 0, 0.25, 0.5, 0.75, 1.0, 1.5, 2 , 3, 4, 6, 8 and 12 h hours post-dose on Day 1 and Day 14 |
|
|
|
| 0 |
| 4 |
| 0 |
| 4 |
| 3 |
| 4 |
| EG001 | B - Second Dose Level (n=10) | nikkomycin Z nikkomycin Z 250 mg BID x 14 days nikkomycin Z: Stage I: Multiple rising doses. Doses packaged on a unit dose basis in 50 and 250 mg capsules. Subjects take 1-3 capsules per dosing block for 14 days unless ADE or study withdrawal. Dose escalation unless a dose-limiting adverse effect is noted. Subjects assigned to BID dosing will receive 28 doses and subjects assigned to TID dosing will receive 42 doses.
At least 4 subjects complete lower dose before randomization includes next higher dose. Stage II will be a single dose level selected based on pharmacodynamics and safety from Stage I for 20 additional subjects using 4:1 randomization. | 0 | 1 | 0 | 1 | 1 | 1 |
| EG002 | C - Third Dose Level (n=10) | nikkomycin Z 500 mg BID x 14 days nikkomycin Z: Stage I: Multiple rising doses. Doses packaged on a unit dose basis in 50 and 250 mg capsules. Subjects take 1-3 capsules per dosing block for 14 days unless ADE or study withdrawal. Dose escalation unless a dose-limiting adverse effect is noted. Subjects assigned to BID dosing will receive 28 doses and subjects assigned to TID dosing will receive 42 doses.
At least 4 subjects complete lower dose before randomization includes next higher dose. Stage II will be a single dose level selected based on pharmacodynamics and safety from Stage I for 20 additional subjects using 4:1 randomization. | 0 | 0 | 0 | 0 | 0 | 0 |
| EG003 | D - Fourth Dose Level (n=5) | nikkomycin Z 750 BID x 14 days nikkomycin Z: Stage I: Multiple rising doses. Doses packaged on a unit dose basis in 50 and 250 mg capsules. Subjects take 1-3 capsules per dosing block for 14 days unless ADE or study withdrawal. Dose escalation unless a dose-limiting adverse effect is noted. Subjects assigned to BID dosing will receive 28 doses and subjects assigned to TID dosing will receive 42 doses.
At least 4 subjects complete lower dose before randomization includes next higher dose. Stage II will be a single dose level selected based on pharmacodynamics and safety from Stage I for 20 additional subjects using 4:1 randomization. | 0 | 0 | 0 | 0 | 0 | 0 |
| EG004 | Placebo | placebo BID x 14 days Placebo: Placebo comparator | 0 | 1 | 0 | 1 | 1 | 1 |
| Near syncope | General disorders | Systematic Assessment |
|
| Headache | General disorders | Systematic Assessment |
|
| Diarrhea | Gastrointestinal disorders | Systematic Assessment |
|
| Dry mouth | General disorders | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | Systematic Assessment |
|
| Insomnia | General disorders | Systematic Assessment |
|
| Cataract surgery | Eye disorders | Systematic Assessment |
|
| Left lung nodule | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Right temple pain | General disorders | Systematic Assessment |
|
Not provided
Not provided
Not provided