Trial Outcomes & Findings for Safety and PK of Nikkomycin Z for Coccidioides Pneumonia Treatment (NCT NCT00614666)
NCT ID: NCT00614666
Last Updated: 2025-04-16
Results Overview
Recruitment status
TERMINATED
Study phase
PHASE1/PHASE2
Target enrollment
6 participants
Primary outcome timeframe
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
Results posted on
2025-04-16
Participant Flow
Participant milestones
| Measure |
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.
* 50 mg BID vs placebo capsule BID
* 50 mg BID vs 250 mg BID vs Placebo capsule BID
* 250 mg BID vs 500 mg BID vs Placebo capsule BID
* 500 mg BID vs Placebo capsule BID
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.
|
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.
* 50 mg BID vs placebo capsule BID
* 50 mg BID vs 250 mg BID vs Placebo capsule BID
* 250 mg BID vs 500 mg BID vs Placebo capsule BID
* 500 mg BID vs Placebo capsule BID
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.
|
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.
* 50 mg BID vs placebo capsule BID
* 50 mg BID vs 250 mg BID vs Placebo capsule BID
* 250 mg BID vs 500 mg BID vs Placebo capsule BID
* 500 mg BID vs Placebo capsule BID
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.
|
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.
* 50 mg BID vs placebo capsule BID
* 50 mg BID vs 250 mg BID vs Placebo capsule BID
* 250 mg BID vs 500 mg BID vs Placebo capsule BID
* 500 mg BID vs Placebo capsule BID
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
placebo BID x 14 days
Placebo: Placebo comparator
|
|---|---|---|---|---|---|
|
Overall Study
STARTED
|
4
|
1
|
0
|
0
|
1
|
|
Overall Study
COMPLETED
|
4
|
1
|
0
|
0
|
1
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Safety and PK of Nikkomycin Z for Coccidioides Pneumonia Treatment
Baseline characteristics by cohort
| Measure |
A - First Dose Level (n=5)
n=4 Participants
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.
* 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.
|
B - Second Dose Level (n=10)
n=1 Participants
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.
* 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.
|
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.
* 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.
|
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.
* 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
n=1 Participants
placebo BID x 14 days
Placebo: Placebo comparator
|
Total
n=6 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|---|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=10 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=10 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=10 Participants
|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=10 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
4 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
1 Participants
n=21 Participants
|
6 Participants
n=10 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=10 Participants
|
|
Sex: Female, Male
Female
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
1 Participants
n=21 Participants
|
2 Participants
n=10 Participants
|
|
Sex: Female, Male
Male
|
3 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
4 Participants
n=10 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=10 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
4 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
1 Participants
n=21 Participants
|
6 Participants
n=10 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=10 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=10 Participants
|
|
Race (NIH/OMB)
White
|
4 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
1 Participants
n=21 Participants
|
6 Participants
n=10 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=10 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=10 Participants
|
|
Region of Enrollment
United States
|
4 participants
n=5 Participants
|
1 participants
n=7 Participants
|
—
|
—
|
1 participants
n=21 Participants
|
6 participants
n=10 Participants
|
PRIMARY outcome
Timeframe: 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 14Population: The study was terminated after enrollment of 6 subjects
Outcome measures
| Measure |
A - First Dose Level (n=5)
n=4 Participants
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.
* 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.
|
B - Second Dose Level (n=10)
n=1 Participants
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.
* 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.
|
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.
* 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.
|
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.
* 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.
|
|---|---|---|---|---|
|
Concentration of Nikkomycin Z in the Blood Over Time (AUC)
Day 1
|
3.444 mg*hr/L
Standard Deviation 0.710
|
19.923 mg*hr/L
Standard Deviation NA
Standard Deviation not calculable for 1 participant
|
—
|
—
|
|
Concentration of Nikkomycin Z in the Blood Over Time (AUC)
Day 14
|
3.900 mg*hr/L
Standard Deviation 1.583
|
24.045 mg*hr/L
Standard Deviation NA
Standard Deviation not calculable for 1 participant
|
—
|
—
|
PRIMARY outcome
Timeframe: 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 14Population: The study was terminated after enrollment of 6 subjects
Outcome measures
| Measure |
A - First Dose Level (n=5)
n=4 Participants
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.
* 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.
|
B - Second Dose Level (n=10)
n=1 Participants
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.
* 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.
|
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.
* 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.
|
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.
* 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.
|
|---|---|---|---|---|
|
Highest Concentration of Nikkomycin Z in the Blood (Cmax)
Day 1
|
0.710 mg/L
Standard Deviation 0.188
|
3.748 mg/L
Standard Deviation NA
Standard Deviation not calculable for 1 participant
|
—
|
—
|
|
Highest Concentration of Nikkomycin Z in the Blood (Cmax)
Day 14
|
0.811 mg/L
Standard Deviation 0.248
|
4.275 mg/L
Standard Deviation NA
Standard Deviation not calculable for 1 participant
|
—
|
—
|
Adverse Events
A - First Dose Level (n=5)
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
B - Second Dose Level (n=10)
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
C - Third Dose Level (n=10)
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
D - Fourth Dose Level (n=5)
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Placebo
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
A - First Dose Level (n=5)
n=4 participants at risk
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.
* 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.
|
B - Second Dose Level (n=10)
n=1 participants at risk
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.
* 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.
|
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.
* 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.
|
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.
* 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
n=1 participants at risk
placebo BID x 14 days
Placebo: Placebo comparator
|
|---|---|---|---|---|---|
|
Vascular disorders
Hypotension
|
25.0%
1/4 • Number of events 1
|
0.00%
0/1
|
—
0/0
|
—
0/0
|
0.00%
0/1
|
|
General disorders
Near syncope
|
25.0%
1/4 • Number of events 1
|
0.00%
0/1
|
—
0/0
|
—
0/0
|
0.00%
0/1
|
|
General disorders
Headache
|
75.0%
3/4 • Number of events 6
|
100.0%
1/1 • Number of events 1
|
—
0/0
|
—
0/0
|
100.0%
1/1 • Number of events 5
|
|
Gastrointestinal disorders
Diarrhea
|
25.0%
1/4 • Number of events 1
|
0.00%
0/1
|
—
0/0
|
—
0/0
|
0.00%
0/1
|
|
General disorders
Dry mouth
|
25.0%
1/4 • Number of events 1
|
0.00%
0/1
|
—
0/0
|
—
0/0
|
0.00%
0/1
|
|
Gastrointestinal disorders
Nausea
|
25.0%
1/4 • Number of events 1
|
0.00%
0/1
|
—
0/0
|
—
0/0
|
100.0%
1/1 • Number of events 1
|
|
General disorders
Insomnia
|
25.0%
1/4 • Number of events 1
|
0.00%
0/1
|
—
0/0
|
—
0/0
|
0.00%
0/1
|
|
Eye disorders
Cataract surgery
|
25.0%
1/4 • Number of events 1
|
0.00%
0/1
|
—
0/0
|
—
0/0
|
0.00%
0/1
|
|
Respiratory, thoracic and mediastinal disorders
Left lung nodule
|
0.00%
0/4
|
100.0%
1/1 • Number of events 1
|
—
0/0
|
—
0/0
|
0.00%
0/1
|
|
General disorders
Right temple pain
|
0.00%
0/4
|
100.0%
1/1 • Number of events 1
|
—
0/0
|
—
0/0
|
0.00%
0/1
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place