Trial Outcomes & Findings for Weekly Dosing of Malarone ® for Prevention of Malaria (NCT NCT00984256)
NCT ID: NCT00984256
Last Updated: 2013-11-25
Results Overview
Number of participants with prophylactic efficacy was determined by the absence of cases of malaria parasitemia, defined as microscopically detectable parasitemia by Giemsa-stained thick smears, in those receiving any dose of Malarone as compared to the control (no treatment) group
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
35 participants
Primary outcome timeframe
Days 6-20
Results posted on
2013-11-25
Participant Flow
Study subjects were healthy male and non-pregnant or lactating females between the ages of 18 and 50 with a body mass index (BMI)between 19 and 30 for subject receiving the drug.
Participant milestones
| Measure |
Control
The six volunteers in control cohort were enrolled as infectivity controls and did not undergo randomization or receive any study drug.
|
Malarone Treatment
Within the Malarone Arm, thirty volunteers were randomized into the below 5 treatment groups, each group receiving Malarone tablet(s) (250/100mg)prior to challenge.
Group 1 - 1 tablet 1 day before challenge Group 2 - 1 tablet 4 days before challenge Group 3 - 1 tablet 7 days before challenge Group 4 - 2 tablets 7 days before challenge Group 5 - 4 tablets 7 days before challenge
|
|---|---|---|
|
Overall Study
STARTED
|
6
|
30
|
|
Overall Study
COMPLETED
|
6
|
29
|
|
Overall Study
NOT COMPLETED
|
0
|
1
|
Reasons for withdrawal
| Measure |
Control
The six volunteers in control cohort were enrolled as infectivity controls and did not undergo randomization or receive any study drug.
|
Malarone Treatment
Within the Malarone Arm, thirty volunteers were randomized into the below 5 treatment groups, each group receiving Malarone tablet(s) (250/100mg)prior to challenge.
Group 1 - 1 tablet 1 day before challenge Group 2 - 1 tablet 4 days before challenge Group 3 - 1 tablet 7 days before challenge Group 4 - 2 tablets 7 days before challenge Group 5 - 4 tablets 7 days before challenge
|
|---|---|---|
|
Overall Study
Withdrawal by Subject
|
0
|
1
|
Baseline Characteristics
Weekly Dosing of Malarone ® for Prevention of Malaria
Baseline characteristics by cohort
| Measure |
Malarone
n=29 Participants
Thirty (30) subjects were placed in the Malarone (treatment) Arm. The thirty subjects were then randomized into 5 treatment groups, each group receiving Malarone tablet(s) (250/100mg)prior to challenge. The groups received treatment as follows:
Group 1 - 1 tablet 1 day before challenge Group 2 - 1 tablet 4 days before challenge Group 3 - 1 tablet 7 days before challenge Group 4 - 2 tablets 7 days before challenge Group 5 - 4 tablets 7 days before challenge
|
Control
n=6 Participants
The six (6) Control volunteers were enrolled in a open label arm and received no treatment prior to malaria challenge.
|
Total
n=35 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
29 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
35 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
11 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
12 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
18 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
23 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
29 participants
n=5 Participants
|
6 participants
n=7 Participants
|
35 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Days 6-20Population: Analysis population was "According to Protocol" which included participants meeting all eligibility criteria, not meeting any elimination criteria, complying with defined protocol procedures and for whom data are available.
Number of participants with prophylactic efficacy was determined by the absence of cases of malaria parasitemia, defined as microscopically detectable parasitemia by Giemsa-stained thick smears, in those receiving any dose of Malarone as compared to the control (no treatment) group
Outcome measures
| Measure |
Treatment Group 1
n=6 Participants
(Group 1) Malarone 1 tablet (250/100 mg) orally administered once 1 day prior to challenge
|
Treatment Group 2
n=4 Participants
(Group 2) Malarone 1 tablet (250/100 mg) orally administered once on day 4 after challenge
|
Treatment Group 3
n=5 Participants
(Group 3) Malarone 1 tablets (250/100 mg) orally administered once 7 days prior to challenge
|
Treatment Group 4
n=6 Participants
(Group 4) Malarone 2 tablets (500/200 mg) orally administered once 7 days prior to challenge
|
Treatment Group 5
n=6 Participants
(Group 5) Malarone 4 tablets (1000/400 mg) orally administered once 7 days prior to challenge
|
Control
n=6 Participants
Six volunteers for the control cohort were enrolled as an infectivity control and did not undergo drug dosing.
|
|---|---|---|---|---|---|---|
|
Prophylactic Efficacy of 3 Different Doses of Atovaquone/Proguanil (Malarone@) Given 1 Week Before Infectious Sporozoite Challenge Using the P. Falciparum Human Challenge Model.
|
6 participants with negative parasitemia
|
4 participants with negative parasitemia
|
3 participants with negative parasitemia
|
6 participants with negative parasitemia
|
5 participants with negative parasitemia
|
0 participants with negative parasitemia
|
SECONDARY outcome
Timeframe: 7, 6, 5, and 1 day prior to challenge; on the day of the challenge; 1, 4, 5, 6, 7, 8, 10and 14 days after the challenge; and on the day parasitemia develops.,Population: Population for analysis included According to Protocol Population.
Plasma concentrations (ng/ml) were used to determine the elimination half life (t1/2) of atovaquone (days).
Outcome measures
| Measure |
Treatment Group 1
n=6 Participants
(Group 1) Malarone 1 tablet (250/100 mg) orally administered once 1 day prior to challenge
|
Treatment Group 2
n=4 Participants
(Group 2) Malarone 1 tablet (250/100 mg) orally administered once on day 4 after challenge
|
Treatment Group 3
n=5 Participants
(Group 3) Malarone 1 tablets (250/100 mg) orally administered once 7 days prior to challenge
|
Treatment Group 4
n=6 Participants
(Group 4) Malarone 2 tablets (500/200 mg) orally administered once 7 days prior to challenge
|
Treatment Group 5
n=6 Participants
(Group 5) Malarone 4 tablets (1000/400 mg) orally administered once 7 days prior to challenge
|
Control
Six volunteers for the control cohort were enrolled as an infectivity control and did not undergo drug dosing.
|
|---|---|---|---|---|---|---|
|
Measured Concentrations of Plasma Atovaquone With Determinations of T1/2.
|
3.3 Days
Standard Deviation 1.9
|
3.3 Days
Standard Deviation 1.2
|
3.3 Days
Standard Deviation 1.6
|
5.6 Days
Standard Deviation 3.1
|
3.7 Days
Standard Deviation 1.4
|
—
|
SECONDARY outcome
Timeframe: 7, 6, 5, and 1 day prior to challenge; on the day of the challenge; 1, 4, 5, 6, 7, 8, 10and 14 days after the challenge; and on the day parasitemia develops.,Population: Analysis was done on subjects who completed the study according to protocol
Plasma concentrations were used to determine the pharmacokinetic curves with determinations of area under the curve (AUC).The smallest AUC Day 0-6.5 associated with protection from detectable parasitemia, and the highest AUC Day 0-6.5 observed in any cases of malaria (prophylactic failures) were to be reported.
Outcome measures
| Measure |
Treatment Group 1
n=6 Participants
(Group 1) Malarone 1 tablet (250/100 mg) orally administered once 1 day prior to challenge
|
Treatment Group 2
n=4 Participants
(Group 2) Malarone 1 tablet (250/100 mg) orally administered once on day 4 after challenge
|
Treatment Group 3
n=5 Participants
(Group 3) Malarone 1 tablets (250/100 mg) orally administered once 7 days prior to challenge
|
Treatment Group 4
n=6 Participants
(Group 4) Malarone 2 tablets (500/200 mg) orally administered once 7 days prior to challenge
|
Treatment Group 5
n=6 Participants
(Group 5) Malarone 4 tablets (1000/400 mg) orally administered once 7 days prior to challenge
|
Control
Six volunteers for the control cohort were enrolled as an infectivity control and did not undergo drug dosing.
|
|---|---|---|---|---|---|---|
|
Measured Concentrations of Plasma Atovaquone With Determinations of Area Under the Curve
|
3595 ng*day/ml
Standard Deviation 2213
|
616 ng*day/ml
Standard Deviation 191
|
510 ng*day/ml
Standard Deviation 218
|
1434 ng*day/ml
Standard Deviation 664
|
2233 ng*day/ml
Standard Deviation 1895
|
—
|
Adverse Events
Drug
Serious events: 0 serious events
Other events: 16 other events
Deaths: 0 deaths
Control
Serious events: 0 serious events
Other events: 6 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Drug
n=29 participants at risk
Partially randomized, double-blind, placebo-controlled trial using a human Plasmodium falciparum challenge to evaluate malaria chemoprophylaxis of Malarone in 36 healthy adults. Subjects were enrolled in 1 of 2 cohorts based on subject preference. Thirty subjects were placed in the prophylaxis cohort (Cohort 1) and 6 subjects were placed in the control cohort (Cohort 2)
5 treatment groups, each group receiving Malarone tablet(s) (250/100mg)prior to challenge.
Group 1 - 1 tablet 1 day before challenge Group 2 - 1 tablet 4 days before challenge Group 3 - 1 tablet 7 days before challenge Group 4 - 2 tablets 7 days before challenge Group 5 - 4 tablets 7 days before challenge
|
Control
n=6 participants at risk
no malarone prophylaxis received
|
|---|---|---|
|
General disorders
|
0.00%
0/29 • 7 days before challenge until end of the study (Day 90)
|
0.00%
0/6 • 7 days before challenge until end of the study (Day 90)
|
Other adverse events
| Measure |
Drug
n=29 participants at risk
Partially randomized, double-blind, placebo-controlled trial using a human Plasmodium falciparum challenge to evaluate malaria chemoprophylaxis of Malarone in 36 healthy adults. Subjects were enrolled in 1 of 2 cohorts based on subject preference. Thirty subjects were placed in the prophylaxis cohort (Cohort 1) and 6 subjects were placed in the control cohort (Cohort 2)
5 treatment groups, each group receiving Malarone tablet(s) (250/100mg)prior to challenge.
Group 1 - 1 tablet 1 day before challenge Group 2 - 1 tablet 4 days before challenge Group 3 - 1 tablet 7 days before challenge Group 4 - 2 tablets 7 days before challenge Group 5 - 4 tablets 7 days before challenge
|
Control
n=6 participants at risk
no malarone prophylaxis received
|
|---|---|---|
|
Nervous system disorders
Headache
|
51.7%
15/29 • Number of events 22 • 7 days before challenge until end of the study (Day 90)
|
33.3%
2/6 • Number of events 2 • 7 days before challenge until end of the study (Day 90)
|
|
Respiratory, thoracic and mediastinal disorders
upper respiratory infection
|
31.0%
9/29 • Number of events 9 • 7 days before challenge until end of the study (Day 90)
|
83.3%
5/6 • Number of events 5 • 7 days before challenge until end of the study (Day 90)
|
Additional Information
Michelle Mathers
US Army Medical Materiel Development Activity (USAMMDA)
Phone: 301-619-8061
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place