A Phase 1/2 interventional study of nikkomycin Z and Placebo in Coccidioidomycosis, sponsored by University of Arizona. Terminated at 1 site in United States. Open to participants aged 18 Years to 50 Years. Per ClinicalTrials.gov, last updated 2025-04-16.
Sponsored by University of Arizona · Phase 1/2, Interventional, and Treatment
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.
Exclusion Criteria:
nikkomycin Z 50 mg BID x 14 days
Drug: nikkomycin Z
nikkomycin Z nikkomycin Z 250 mg BID x 14 days
Drug: nikkomycin Z
nikkomycin Z 500 mg BID x 14 days
Drug: nikkomycin Z
nikkomycin Z 750 BID x 14 days
Drug: nikkomycin Z
placebo BID x 14 days
Drug: Placebo
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. * 50 mg BID (n=4) vs placebo capsule BID (n=1) * 50 mg BID (n=4) vs 250 mg BID (n=4) vs Placebo capsule BID (n=2) * 250 mg BID (n=4) vs 500 mg BID (n=4) vs Placebo capsule BID (n=2) * 500 mg BID (n=4) vs Placebo capsule BID (n=1) 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.
Placebo comparator
Concentration of Nikkomycin Z in the Blood Over Time (AUC)
Time frame: 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)
Time frame: 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
| Milestone | A - First Dose Level | B - Second Dose Level | C - Third Dose Level | D - Fourth Dose Level | Placebo |
|---|---|---|---|---|---|
| Started | 4 | 1 | 0 | 0 | 1 |
| Completed | 4 | 1 | 0 | 0 | 1 |
| Not completed | 0 | 0 | 0 | 0 | 0 |
| mg*hr/L | A - First Dose Level (n=5) | B - Second Dose Level (n=10) | C - Third Dose Level (n=10) | D - Fourth Dose Level (n=5) |
|---|---|---|---|---|
| Day 1 | 3.444 ± 0.710 | 19.923 ± NA | — | — |
| Day 14 | 3.900 ± 1.583 | 24.045 ± NA | — | — |
| mg/L | A - First Dose Level (n=5) | B - Second Dose Level (n=10) | C - Third Dose Level (n=10) | D - Fourth Dose Level (n=5) |
|---|---|---|---|---|
| Day 1 | 0.710 ± 0.188 | 3.748 ± NA | — | — |
| Day 14 | 0.811 ± 0.248 | 4.275 ± NA | — | — |
Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| A - First Dose Level (n=5) | 0/4 (0%) | 0/4 (0%) | 3/4 (75%) |
| B - Second Dose Level (n=10) | 0/1 (0%) | 0/1 (0%) | 1/1 (100%) |
| C - Third Dose Level (n=10) | — | — | — |
| D - Fourth Dose Level (n=5) | — | — | — |
| Placebo | 0/1 (0%) | 0/1 (0%) | 1/1 (100%) |
| Event | A - First Dose Level (n=5) | B - Second Dose Level (n=10) | C - Third Dose Level (n=10) | D - Fourth Dose Level (n=5) | Placebo |
|---|---|---|---|---|---|
| HeadacheGeneral disorders | 3/4 | 1/1 | — | — | 1/1 |
| NauseaGastrointestinal disorders | 1/4 | 0/1 | — | — | 1/1 |
| Left lung noduleRespiratory, thoracic and mediastinal disorders | 0/4 | 1/1 | — | — | 0/1 |
| Right temple painGeneral disorders | 0/4 | 1/1 | — | — | 0/1 |
| HypotensionVascular disorders | 1/4 | 0/1 | — | — | 0/1 |
| Near syncopeGeneral disorders | 1/4 | 0/1 | — | — | 0/1 |
| DiarrheaGastrointestinal disorders | 1/4 | 0/1 | — | — | 0/1 |
| Dry mouthGeneral disorders | 1/4 | 0/1 | — | — | 0/1 |
| InsomniaGeneral disorders | 1/4 | 0/1 | — | — | 0/1 |
| Cataract surgeryEye disorders | 1/4 | 0/1 | — | — | 0/1 |
| Age, Categorical(Participants) | A - First Dose Level (n=5) | B - Second Dose Level (n=10) | C - Third Dose Level (n=10) | D - Fourth Dose Level (n=5) | Placebo | Total |
|---|---|---|---|---|---|---|
| <=18 years | 0 | 0 | 0 | 0 | 0 | 0 |
| Between 18 and 65 years | 4 | 1 | 0 | 0 | 1 | 6 |
| >=65 years | 0 | 0 | 0 | 0 | 0 | 0 |
| Sex: Female, Male(Participants) | A - First Dose Level (n=5) | B - Second Dose Level (n=10) | C - Third Dose Level (n=10) | D - Fourth Dose Level (n=5) | Placebo | Total |
|---|---|---|---|---|---|---|
| Female | 1 | 0 | 0 | 0 | 1 | 2 |
| Male | 3 | 1 | 0 | 0 | 0 | 4 |
| Ethnicity (NIH/OMB)(Participants) | A - First Dose Level (n=5) | B - Second Dose Level (n=10) | C - Third Dose Level (n=10) | D - Fourth Dose Level (n=5) | Placebo | Total |
|---|---|---|---|---|---|---|
| Hispanic or Latino | 0 | 0 | 0 | 0 | 0 | 0 |
| Not Hispanic or Latino | 4 | 1 | 0 | 0 | 1 | 6 |
| Unknown or Not Reported | 0 | 0 | 0 | 0 | 0 | 0 |
| Race (NIH/OMB)(Participants) | A - First Dose Level (n=5) | B - Second Dose Level (n=10) | C - Third Dose Level (n=10) | D - Fourth Dose Level (n=5) | Placebo | Total |
|---|---|---|---|---|---|---|
| American Indian or Alaska Native | 0 | 0 | 0 | 0 | 0 | 0 |
| Asian | 0 | 0 | 0 | 0 | 0 | 0 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 | 0 | 0 | 0 |
| Black or African American | 0 | 0 | 0 | 0 | 0 | 0 |
| White | 4 | 1 | 0 | 0 | 1 | 6 |
| More than one race | 0 | 0 | 0 | 0 | 0 | 0 |
| Unknown or Not Reported | 0 | 0 | 0 | 0 | 0 | 0 |
| Region of Enrollment(participants) | A - First Dose Level (n=5) | B - Second Dose Level (n=10) | C - Third Dose Level (n=10) | D - Fourth Dose Level (n=5) | Placebo | Total |
|---|---|---|---|---|---|---|
| United States | 4 | 1 | — | — | 1 | 6 |
Plan to share: Yes — De-identified data may be shared for legitimate use to further nikkomycin Z development.
Supporting information: Study protocol, Icf
This study is terminated, as verified in Jan 2025. You cannot join it, but the record below documents what was studied.
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University of Arizona