Trial Outcomes & Findings for Effectiveness of OZ439 Against Early Plasmodium Falciparum Blood Stage Infection in Healthy Volunteers (NCT NCT02453581)
NCT ID: NCT02453581
Last Updated: 2015-08-17
Results Overview
PRR estimates the efficacy of an anti-malarial treatment and is the ratio of the parasite density between admission and 48 hours post-treatment. Individual subject PRR and corresponding 95% CI were calculated using the slope and corresponding standard error of mean (SE) of the optimal regression model.
COMPLETED
PHASE1
24 participants
48 hours
2015-08-17
Participant Flow
Participant milestones
| Measure |
OZ439 100mg
OZ439 100mg Powder for Oral Suspension
|
OZ439 200mg
OZ439 200mg Powder for Oral Suspension
|
OZ439 500mg
OZ439 500mg Powder for Oral Suspension
|
|---|---|---|---|
|
Overall Study
STARTED
|
8
|
8
|
8
|
|
Overall Study
COMPLETED
|
8
|
8
|
8
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Effectiveness of OZ439 Against Early Plasmodium Falciparum Blood Stage Infection in Healthy Volunteers
Baseline characteristics by cohort
| Measure |
Randomised Participants
n=24 Participants
Twenty-four male and female subjects were enrolled in the study.
|
|---|---|
|
Age, Customized
18 - 30 Years
|
21 participants
n=5 Participants
|
|
Age, Customized
31 - 40 Years
|
3 participants
n=5 Participants
|
|
Age, Customized
41 - 45 Years
|
0 participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
12 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
12 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
24 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
Australia
|
24 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 48 hoursPopulation: As the doses of 100 mg and 200 mg of OZ439 in Cohorts 1 and 2 were inadequate to eliminate the parasites and regrowth occurred, PRR calculations were only undertaken for subjects receiving 500mg of OZ439 in Cohort 3.
PRR estimates the efficacy of an anti-malarial treatment and is the ratio of the parasite density between admission and 48 hours post-treatment. Individual subject PRR and corresponding 95% CI were calculated using the slope and corresponding standard error of mean (SE) of the optimal regression model.
Outcome measures
| Measure |
OZ439 500mg - R017
n=1 Participants
Cohort 3 - OZ439 500mg - Subject R017
|
OZ439 500mg - R018
n=1 Participants
Cohort 3 - OZ439 500mg - Subject R018
|
OZ439 500mg - R019
n=1 Participants
Cohort 3 - OZ439 500mg - Subject R019
|
OZ439 500mg - R020
n=1 Participants
Cohort 3 - OZ439 500mg - Subject R020
|
OZ439 500mg - R021
n=1 Participants
Cohort 3 - OZ439 500mg - Subject R021
|
OZ439 500mg - R022
n=1 Participants
Cohort 3 - OZ439 500mg - Subject R022
|
OZ439 500mg - R023
n=1 Participants
Cohort 3 - OZ439 500mg - Subject R023
|
OZ439 500mg - R024
n=1 Participants
Cohort 3 - OZ439 500mg - Subject R024
|
|---|---|---|---|---|---|---|---|---|
|
Individual Parasite Reduction Ratio (PRR)
|
1132 none (ratio)
Interval 357.0 to 3587.0
|
217646 none (ratio)
Interval 21471.0 to 2206216.0
|
314040 none (ratio)
Interval 42823.0 to 2302975.0
|
8021 none (ratio)
Interval 147.0 to 438967.0
|
8227 none (ratio)
Interval 2665.0 to 25403.0
|
13557 none (ratio)
Interval 3113.0 to 59037.0
|
13560 none (ratio)
Interval 3320.0 to 55381.0
|
21924 none (ratio)
Interval 1486.0 to 323346.0
|
PRIMARY outcome
Timeframe: 48 hoursPopulation: As the doses of 100 mg and 200 mg of OZ439 in Cohorts 1 and 2 were inadequate to eliminate the parasites and regrowth occurred, PRR calculations were only undertaken for subjects receiving 500mg of OZ439 in Cohort 3. With a p value of 0.0046, Subject S036 was excluded from this calculation
OZ439 500mg individual subject PRR and corresponding 95% CI were used to calculate the OZ439 500mg cohort specific PRR and the corresponding 95% CI: the weighted average slope estimate and corresponding SE were calculated by the inverse-variance method.
Outcome measures
| Measure |
OZ439 500mg - R017
n=7 Participants
Cohort 3 - OZ439 500mg - Subject R017
|
OZ439 500mg - R018
Cohort 3 - OZ439 500mg - Subject R018
|
OZ439 500mg - R019
Cohort 3 - OZ439 500mg - Subject R019
|
OZ439 500mg - R020
Cohort 3 - OZ439 500mg - Subject R020
|
OZ439 500mg - R021
Cohort 3 - OZ439 500mg - Subject R021
|
OZ439 500mg - R022
Cohort 3 - OZ439 500mg - Subject R022
|
OZ439 500mg - R023
Cohort 3 - OZ439 500mg - Subject R023
|
OZ439 500mg - R024
Cohort 3 - OZ439 500mg - Subject R024
|
|---|---|---|---|---|---|---|---|---|
|
500mg Cohort Mean Parasite Reduction Ratio (PRR)
|
10176 none (ratio)
Interval 5757.0 to 17986.0
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Pre-dose, and 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120 and 144 hours post-dosePopulation: All 24 subjects randomized and completed the study.
OZ439 Maximum concentration (Cmax)
Outcome measures
| Measure |
OZ439 500mg - R017
n=8 Participants
Cohort 3 - OZ439 500mg - Subject R017
|
OZ439 500mg - R018
n=8 Participants
Cohort 3 - OZ439 500mg - Subject R018
|
OZ439 500mg - R019
n=8 Participants
Cohort 3 - OZ439 500mg - Subject R019
|
OZ439 500mg - R020
Cohort 3 - OZ439 500mg - Subject R020
|
OZ439 500mg - R021
Cohort 3 - OZ439 500mg - Subject R021
|
OZ439 500mg - R022
Cohort 3 - OZ439 500mg - Subject R022
|
OZ439 500mg - R023
Cohort 3 - OZ439 500mg - Subject R023
|
OZ439 500mg - R024
Cohort 3 - OZ439 500mg - Subject R024
|
|---|---|---|---|---|---|---|---|---|
|
OZ439 Cmax
|
164 ng/mL
Geometric Coefficient of Variation 20
|
448 ng/mL
Geometric Coefficient of Variation 33
|
1263 ng/mL
Geometric Coefficient of Variation 47
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Pre-dose, and 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120 and 144 hours post-dosePopulation: All 24 subjects randomized and completed the study.
OZ439 Area under the curve to 144 hours
Outcome measures
| Measure |
OZ439 500mg - R017
n=8 Participants
Cohort 3 - OZ439 500mg - Subject R017
|
OZ439 500mg - R018
n=8 Participants
Cohort 3 - OZ439 500mg - Subject R018
|
OZ439 500mg - R019
n=8 Participants
Cohort 3 - OZ439 500mg - Subject R019
|
OZ439 500mg - R020
Cohort 3 - OZ439 500mg - Subject R020
|
OZ439 500mg - R021
Cohort 3 - OZ439 500mg - Subject R021
|
OZ439 500mg - R022
Cohort 3 - OZ439 500mg - Subject R022
|
OZ439 500mg - R023
Cohort 3 - OZ439 500mg - Subject R023
|
OZ439 500mg - R024
Cohort 3 - OZ439 500mg - Subject R024
|
|---|---|---|---|---|---|---|---|---|
|
OZ439 AUC(0-144)
|
1056 ng*h/mL
Geometric Coefficient of Variation 23
|
3182 ng*h/mL
Geometric Coefficient of Variation 21
|
10755 ng*h/mL
Geometric Coefficient of Variation 40
|
—
|
—
|
—
|
—
|
—
|
Adverse Events
OZ439 100mg
OZ439 200mg
OZ439 500mg
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
OZ439 100mg
n=8 participants at risk
OZ439 100mg Powder for Oral Suspension
|
OZ439 200mg
n=8 participants at risk
OZ439 200mg Powder for Oral Suspension
|
OZ439 500mg
n=8 participants at risk
OZ439 500mg Powder for Oral Suspension
|
|---|---|---|---|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/8 • 144 hours
24 subjects who participated in the study.
|
12.5%
1/8 • Number of events 1 • 144 hours
24 subjects who participated in the study.
|
0.00%
0/8 • 144 hours
24 subjects who participated in the study.
|
|
Nervous system disorders
Headache
|
0.00%
0/8 • 144 hours
24 subjects who participated in the study.
|
12.5%
1/8 • Number of events 1 • 144 hours
24 subjects who participated in the study.
|
12.5%
1/8 • Number of events 2 • 144 hours
24 subjects who participated in the study.
|
|
Cardiac disorders
Rapid Regular Heart Rate
|
12.5%
1/8 • Number of events 1 • 144 hours
24 subjects who participated in the study.
|
0.00%
0/8 • 144 hours
24 subjects who participated in the study.
|
0.00%
0/8 • 144 hours
24 subjects who participated in the study.
|
|
Psychiatric disorders
Difficulty Focusing
|
0.00%
0/8 • 144 hours
24 subjects who participated in the study.
|
12.5%
1/8 • Number of events 1 • 144 hours
24 subjects who participated in the study.
|
0.00%
0/8 • 144 hours
24 subjects who participated in the study.
|
|
Skin and subcutaneous tissue disorders
Photosensitivity
|
0.00%
0/8 • 144 hours
24 subjects who participated in the study.
|
12.5%
1/8 • Number of events 1 • 144 hours
24 subjects who participated in the study.
|
0.00%
0/8 • 144 hours
24 subjects who participated in the study.
|
Additional Information
Dr James McCarthy
Qeensland Institute of Medical Research
Results disclosure agreements
- Principal investigator is a sponsor employee Publication and reporting of results and outcomes of this trial will be accurate and honest, undertaken with integrity and transparency and in accordance with QIMR's Policy on Criteria for Authorship. Publication of results will be subjected to fair peer-review. Data will not be released publicly until the manuscript is accepted for publication.
- Publication restrictions are in place
Restriction type: OTHER