Trial Outcomes & Findings for Assess Safety, Tolerability, Pharmacokinetic and Pharmacodynamic Profile of Ruxolitinib With Artemether-lumefantrine (NCT NCT04456634)
NCT ID: NCT04456634
Last Updated: 2021-07-09
Results Overview
Incidence, severity and relationship of observed and self-reported adverse events (AEs) were reported during the study up to 28 days after AL+Rux and AL+Placebo administration in all participants by treatment regimens.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
8 participants
Primary outcome timeframe
up to 28 days after AL+Rux and AL+placebo administration
Results posted on
2021-07-09
Participant Flow
A total of 8 eligible participants were recruited at in the time period between 24 Aug 2020 and 19 Oct 2020 at Nucleus Network Brisbane clinic.
No wash out phase, no run-in phase. All eligible participants were dosed to the allocated doses on day 1. The study was composed of 2 groups to be enrolled sequentially.
Participant milestones
| Measure |
AL&RUX
Oral administration of:
• 20 mg/120 mg artemether-lumefantrine (AL) + 20 mg ruxolitinib phosphate (Rux)
20 mg/120 mg artemether-lumefantrine (AL) + 20 mg ruxolitinib phosphate (Rux): Rux administered 2 hours after AL administration, twice daily (b.i.d) for 3 consecutive days (6 doses in total).
|
AL& Placebo
20 mg/120 mg artemether-lumefantrine (AL) + Placebo
20 mg/120 mg artemether-lumefantrine (AL) + Placebo: Placebo administered 2 hours after AL administration, twice daily (b.i.d) for 3 consecutive days (6 doses in total).
|
|---|---|---|
|
Overall Study
STARTED
|
6
|
2
|
|
Overall Study
COMPLETED
|
5
|
2
|
|
Overall Study
NOT COMPLETED
|
1
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Assess Safety, Tolerability, Pharmacokinetic and Pharmacodynamic Profile of Ruxolitinib With Artemether-lumefantrine
Baseline characteristics by cohort
| Measure |
AL&RUX
n=6 Participants
Oral administration of:
• 20 mg/120 mg artemether-lumefantrine (AL) + 20 mg ruxolitinib phosphate (Rux)
20 mg/120 mg artemether-lumefantrine (AL) + 20 mg ruxolitinib phosphate (Rux): Rux administered 2 hours after AL administration, twice daily (b.i.d) for 3 consecutive days (6 doses in total).
|
AL& Placebo
n=2 Participants
20 mg/120 mg artemether-lumefantrine (AL) + Placebo
20 mg/120 mg artemether-lumefantrine (AL) + Placebo: Placebo administered 2 hours after AL administration, twice daily (b.i.d) for 3 consecutive days (6 doses in total).
|
Total
n=8 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
|
6 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
8 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Continuous
|
26.3 years
STANDARD_DEVIATION 11.8 • n=5 Participants
|
30.0 years
STANDARD_DEVIATION 12.7 • n=7 Participants
|
27.3 years
STANDARD_DEVIATION 27.3 • n=5 Participants
|
|
Sex: Female, Male
Female
|
4 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
2 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
5 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
Australia
|
6 participants
n=5 Participants
|
2 participants
n=7 Participants
|
8 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: up to 28 days after AL+Rux and AL+placebo administrationPopulation: All participants who received at least one dose of treatment
Incidence, severity and relationship of observed and self-reported adverse events (AEs) were reported during the study up to 28 days after AL+Rux and AL+Placebo administration in all participants by treatment regimens.
Outcome measures
| Measure |
AL&RUX
n=6 Participants
Oral administration of:
• 20 mg/120 mg artemether-lumefantrine (AL) + 20 mg ruxolitinib phosphate (Rux)
20 mg/120 mg artemether-lumefantrine (AL) + 20 mg ruxolitinib phosphate (Rux): Rux administered 2 hours after AL administration, twice daily (b.i.d) for 3 consecutive days (6 doses in total).
|
AL& Placebo
n=2 Participants
20 mg/120 mg artemether-lumefantrine (AL) + Placebo
20 mg/120 mg artemether-lumefantrine (AL) + Placebo: Placebo administered 2 hours after AL administration, twice daily (b.i.d) for 3 consecutive days (6 doses in total).
|
|---|---|---|
|
Number of Participant With Treatment-Related Adverse Events as Assessed by CTCAE V4.03, All of Observed and Self-reported AEs Affected, by Treatment Regimen.
|
6 Participants
|
2 Participants
|
PRIMARY outcome
Timeframe: up to 28 days after AL+Rux and AL+placebo administrationPopulation: All participants who received at least one dose of treatment
Safety signals, trends or significant differences in blood pressure between treatment groups were were reported during the study up to 28 days after AL+Rux and AL+Placebo administration in all participants by treatment regimens.
Outcome measures
| Measure |
AL&RUX
n=6 Participants
Oral administration of:
• 20 mg/120 mg artemether-lumefantrine (AL) + 20 mg ruxolitinib phosphate (Rux)
20 mg/120 mg artemether-lumefantrine (AL) + 20 mg ruxolitinib phosphate (Rux): Rux administered 2 hours after AL administration, twice daily (b.i.d) for 3 consecutive days (6 doses in total).
|
AL& Placebo
n=2 Participants
20 mg/120 mg artemether-lumefantrine (AL) + Placebo
20 mg/120 mg artemether-lumefantrine (AL) + Placebo: Placebo administered 2 hours after AL administration, twice daily (b.i.d) for 3 consecutive days (6 doses in total).
|
|---|---|---|
|
Number of Participants With Changes of Systolic and Diastolic Blood Pressure
|
2 Participants
|
0 Participants
|
PRIMARY outcome
Timeframe: up to 28 days after AL+Rux and AL+placebo administrationPopulation: All participants who received at least one dose of treatment
Safety signals, trends or significant differences in heart rate ( beats / min)between treatment groups were were reported during the study up to 28 days after AL+Rux and AL+Placebo administration in all participants by treatment regimens.
Outcome measures
| Measure |
AL&RUX
n=6 Participants
Oral administration of:
• 20 mg/120 mg artemether-lumefantrine (AL) + 20 mg ruxolitinib phosphate (Rux)
20 mg/120 mg artemether-lumefantrine (AL) + 20 mg ruxolitinib phosphate (Rux): Rux administered 2 hours after AL administration, twice daily (b.i.d) for 3 consecutive days (6 doses in total).
|
AL& Placebo
n=2 Participants
20 mg/120 mg artemether-lumefantrine (AL) + Placebo
20 mg/120 mg artemether-lumefantrine (AL) + Placebo: Placebo administered 2 hours after AL administration, twice daily (b.i.d) for 3 consecutive days (6 doses in total).
|
|---|---|---|
|
Number of Participants With Changes in Heart Rate
|
1 Participants
|
0 Participants
|
PRIMARY outcome
Timeframe: up to 28 days after AL+Rux and AL+placebo administrationPopulation: All participants who received at least one dose of treatment
Safety signals, trends or significant differences in QT, QTcB and QTcF, QRS between treatment groups were were reported during the study up to 28 days after AL+Rux and AL+Placebo administration in all participants by treatment regimens.
Outcome measures
| Measure |
AL&RUX
n=6 Participants
Oral administration of:
• 20 mg/120 mg artemether-lumefantrine (AL) + 20 mg ruxolitinib phosphate (Rux)
20 mg/120 mg artemether-lumefantrine (AL) + 20 mg ruxolitinib phosphate (Rux): Rux administered 2 hours after AL administration, twice daily (b.i.d) for 3 consecutive days (6 doses in total).
|
AL& Placebo
n=2 Participants
20 mg/120 mg artemether-lumefantrine (AL) + Placebo
20 mg/120 mg artemether-lumefantrine (AL) + Placebo: Placebo administered 2 hours after AL administration, twice daily (b.i.d) for 3 consecutive days (6 doses in total).
|
|---|---|---|
|
Number of Participants With ECG Changes
|
2 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: up to 28 days after AL+Rux and AL+placebo administrationPopulation: All participants who received at least one dose of treatment
Area under the effect curve (AUECt) of pSTAT3 inhibition levels
Outcome measures
| Measure |
AL&RUX
n=6 Participants
Oral administration of:
• 20 mg/120 mg artemether-lumefantrine (AL) + 20 mg ruxolitinib phosphate (Rux)
20 mg/120 mg artemether-lumefantrine (AL) + 20 mg ruxolitinib phosphate (Rux): Rux administered 2 hours after AL administration, twice daily (b.i.d) for 3 consecutive days (6 doses in total).
|
AL& Placebo
n=2 Participants
20 mg/120 mg artemether-lumefantrine (AL) + Placebo
20 mg/120 mg artemether-lumefantrine (AL) + Placebo: Placebo administered 2 hours after AL administration, twice daily (b.i.d) for 3 consecutive days (6 doses in total).
|
|---|---|---|
|
AUECt of pSTAT3 Inhibition
|
551 ng.hr/mL
Standard Deviation 86.9
|
186 ng.hr/mL
Standard Deviation 64.1
|
Adverse Events
AL&RUX
Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths
AL& Placebo
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
AL&RUX
n=6 participants at risk
Oral administration of:
• 20 mg/120 mg artemether-lumefantrine (AL) + 20 mg ruxolitinib phosphate (Rux)
20 mg/120 mg artemether-lumefantrine (AL) + 20 mg ruxolitinib phosphate (Rux): Rux administered 2 hours after AL administration, twice daily (b.i.d) for 3 consecutive days (6 doses in total).
|
AL& Placebo
n=2 participants at risk
20 mg/120 mg artemether-lumefantrine (AL) + Placebo
20 mg/120 mg artemether-lumefantrine (AL) + Placebo: Placebo administered 2 hours after AL administration, twice daily (b.i.d) for 3 consecutive days (6 doses in total).
|
|---|---|---|
|
Musculoskeletal and connective tissue disorders
Muscular back pain
|
16.7%
1/6 • Number of events 1 • Adverse events were recorded from time of first dose of IMP until day 29 ( End of study visit) or early termination, approximately 29 days.
|
0.00%
0/2 • Adverse events were recorded from time of first dose of IMP until day 29 ( End of study visit) or early termination, approximately 29 days.
|
|
Nervous system disorders
Headache
|
33.3%
2/6 • Number of events 2 • Adverse events were recorded from time of first dose of IMP until day 29 ( End of study visit) or early termination, approximately 29 days.
|
50.0%
1/2 • Number of events 1 • Adverse events were recorded from time of first dose of IMP until day 29 ( End of study visit) or early termination, approximately 29 days.
|
|
General disorders
Fatigue
|
0.00%
0/6 • Adverse events were recorded from time of first dose of IMP until day 29 ( End of study visit) or early termination, approximately 29 days.
|
50.0%
1/2 • Number of events 1 • Adverse events were recorded from time of first dose of IMP until day 29 ( End of study visit) or early termination, approximately 29 days.
|
|
General disorders
Vessel puncture site bruise
|
16.7%
1/6 • Number of events 1 • Adverse events were recorded from time of first dose of IMP until day 29 ( End of study visit) or early termination, approximately 29 days.
|
0.00%
0/2 • Adverse events were recorded from time of first dose of IMP until day 29 ( End of study visit) or early termination, approximately 29 days.
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
16.7%
1/6 • Number of events 1 • Adverse events were recorded from time of first dose of IMP until day 29 ( End of study visit) or early termination, approximately 29 days.
|
0.00%
0/2 • Adverse events were recorded from time of first dose of IMP until day 29 ( End of study visit) or early termination, approximately 29 days.
|
|
Skin and subcutaneous tissue disorders
Rash maculo-papular
|
0.00%
0/6 • Adverse events were recorded from time of first dose of IMP until day 29 ( End of study visit) or early termination, approximately 29 days.
|
50.0%
1/2 • Number of events 1 • Adverse events were recorded from time of first dose of IMP until day 29 ( End of study visit) or early termination, approximately 29 days.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place