Trial Outcomes & Findings for Darbe Administration in Newborns Undergoing Cooling for Encephalopathy (NCT NCT01471015)
NCT ID: NCT01471015
Last Updated: 2024-07-23
Results Overview
The pharmacokinetic profile of Darbe wil be determined using "population" pharmacokinetic sampling in which babies will be randomized to have blood drawn at different intervals. Serum levels will be drawn at 4,12, 18, 24, 36, 60, and 72 hours post initial dose. Area under the plasma concentration versus time curve (AUC) will be used.
Recruitment status
COMPLETED
Study phase
PHASE1/PHASE2
Target enrollment
30 participants
Primary outcome timeframe
For 72 hours after first dose
Results posted on
2024-07-23
Participant Flow
Participant milestones
| Measure |
High Dose Darbepoetin Alfa
10 mcg/kg/dose Darbe x2 doses, with the first dose within 12 hours of delivery and the second dose at 7 days
Darbepoetin alfa: 10 mcg/kg/dose x2, with the first dose given as IV within 12 hours of delivery and the second dose given as IV or SQ at 7 days old.
|
Low Dose Darbepoetin Alfa
2 mcg/kg/dose Darbe x2, with the first dose given within 12 hours of delivery and the second dose given at 7 days old.
Darbepoetin alfa: 2 mcg/kg/dose x2, with the first dose given IV within 12 hours of delivery and the second dose given IV or SQ at 7 days old.
|
Placebo
Placebo given x2 doses, with the first given within 12 hours of delivery and the second given at 7 days old
Placebo: Placebo given x2, with the first dose given IV within 12 hours of delivery and the second dose given IV or SQ at 7 days old
|
|---|---|---|---|
|
Overall Study
STARTED
|
10
|
10
|
10
|
|
Overall Study
COMPLETED
|
10
|
9
|
9
|
|
Overall Study
NOT COMPLETED
|
0
|
1
|
1
|
Reasons for withdrawal
| Measure |
High Dose Darbepoetin Alfa
10 mcg/kg/dose Darbe x2 doses, with the first dose within 12 hours of delivery and the second dose at 7 days
Darbepoetin alfa: 10 mcg/kg/dose x2, with the first dose given as IV within 12 hours of delivery and the second dose given as IV or SQ at 7 days old.
|
Low Dose Darbepoetin Alfa
2 mcg/kg/dose Darbe x2, with the first dose given within 12 hours of delivery and the second dose given at 7 days old.
Darbepoetin alfa: 2 mcg/kg/dose x2, with the first dose given IV within 12 hours of delivery and the second dose given IV or SQ at 7 days old.
|
Placebo
Placebo given x2 doses, with the first given within 12 hours of delivery and the second given at 7 days old
Placebo: Placebo given x2, with the first dose given IV within 12 hours of delivery and the second dose given IV or SQ at 7 days old
|
|---|---|---|---|
|
Overall Study
Death
|
0
|
1
|
1
|
Baseline Characteristics
Darbe Administration in Newborns Undergoing Cooling for Encephalopathy
Baseline characteristics by cohort
| Measure |
High Dose Darbepoetin Alfa
n=10 Participants
10 mcg/kg/dose Darbe x2 doses, with the first dose within 12 hours of delivery and the second dose at 7 days
Darbepoetin alfa: 10 mcg/kg/dose x2, with the first dose given as IV within 12 hours of delivery and the second dose given as IV or SQ at 7 days old.
|
Low Dose Darbepoetin Alfa
n=10 Participants
2 mcg/kg/dose Darbe x2, with the first dose given within 12 hours of delivery and the second dose given at 7 days old.
Darbepoetin alfa: 2 mcg/kg/dose x2, with the first dose given IV within 12 hours of delivery and the second dose given IV or SQ at 7 days old.
|
Placebo
n=10 Participants
Placebo given x2 doses, with the first given within 12 hours of delivery and the second given at 7 days old
Placebo: Placebo given x2, with the first dose given IV within 12 hours of delivery and the second dose given IV or SQ at 7 days old
|
Total
n=30 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
1 days
n=99 Participants
|
1 days
n=107 Participants
|
1 days
n=206 Participants
|
1 days
n=7 Participants
|
|
Sex: Female, Male
Female
|
4 Participants
n=99 Participants
|
5 Participants
n=107 Participants
|
6 Participants
n=206 Participants
|
15 Participants
n=7 Participants
|
|
Sex: Female, Male
Male
|
6 Participants
n=99 Participants
|
5 Participants
n=107 Participants
|
4 Participants
n=206 Participants
|
15 Participants
n=7 Participants
|
|
Region of Enrollment
United States
|
10 participants
n=99 Participants
|
10 participants
n=107 Participants
|
10 participants
n=206 Participants
|
30 participants
n=7 Participants
|
PRIMARY outcome
Timeframe: For 72 hours after first doseThe pharmacokinetic profile of Darbe wil be determined using "population" pharmacokinetic sampling in which babies will be randomized to have blood drawn at different intervals. Serum levels will be drawn at 4,12, 18, 24, 36, 60, and 72 hours post initial dose. Area under the plasma concentration versus time curve (AUC) will be used.
Outcome measures
| Measure |
High Dose Darbepoetin Alfa
n=10 Participants
10 mcg/kg/dose Darbe x2 doses, with the first dose within 12 hours of delivery and the second dose at 7 days
Darbepoetin alfa: 10 mcg/kg/dose x2, with the first dose given as IV within 12 hours of delivery and the second dose given as IV or SQ at 7 days old.
|
Low Dose Darbepoetin Alfa
n=10 Participants
2 mcg/kg/dose Darbe x2, with the first dose given within 12 hours of delivery and the second dose given at 7 days old.
Darbepoetin alfa: 2 mcg/kg/dose x2, with the first dose given IV within 12 hours of delivery and the second dose given IV or SQ at 7 days old.
|
Placebo
Placebo given x2 doses, with the first given within 12 hours of delivery and the second given at 7 days old
Placebo: Placebo given x2, with the first dose given IV within 12 hours of delivery and the second dose given IV or SQ at 7 days old
|
|---|---|---|---|
|
The Pharmacokinetic Profile of Darbe After the First Dose During Cooling
|
180,866 AUC (h*mU/L)
|
26,555 AUC (h*mU/L)
|
—
|
PRIMARY outcome
Timeframe: For 36 hours after second doseThe pharmacokinetic profile of Darbe will be determined using "population" pharmacokinetic sampling in which babies will be randomized to have blood drawn at different intervals. A second dose of Darbe will be given at 7 days of age, and serum drug levels will be obtained at 12, 18, 24, and 36 hours post second dose. Area under the plasma concentration versus time curve (AUC) will be used.
Outcome measures
| Measure |
High Dose Darbepoetin Alfa
n=10 Participants
10 mcg/kg/dose Darbe x2 doses, with the first dose within 12 hours of delivery and the second dose at 7 days
Darbepoetin alfa: 10 mcg/kg/dose x2, with the first dose given as IV within 12 hours of delivery and the second dose given as IV or SQ at 7 days old.
|
Low Dose Darbepoetin Alfa
n=10 Participants
2 mcg/kg/dose Darbe x2, with the first dose given within 12 hours of delivery and the second dose given at 7 days old.
Darbepoetin alfa: 2 mcg/kg/dose x2, with the first dose given IV within 12 hours of delivery and the second dose given IV or SQ at 7 days old.
|
Placebo
Placebo given x2 doses, with the first given within 12 hours of delivery and the second given at 7 days old
Placebo: Placebo given x2, with the first dose given IV within 12 hours of delivery and the second dose given IV or SQ at 7 days old
|
|---|---|---|---|
|
The Pharmacokinetic Profile of Darbe After the Second Dose.
|
56233 AUC (h*mU/L)
Interval 54915.0 to 71260.0
|
10790 AUC (h*mU/L)
Interval 7043.0 to 13493.0
|
—
|
SECONDARY outcome
Timeframe: 30 days or until hospital dischargePotential adverse events such as (but not limited to) alterations in blood pressure, secondary infections, neutropenia, thrombotic/vascular events, hematologic events (platelets, Hct level, polycythemia), and hepatic/renal function that are outside of normal range for the study population. Complications associated with HIE or cooling therapy will not be considered an AE for this study. AEs reported to be associated with cooling include: bleeding/thrombosis, persistent pulmonary hypertension of the newborn (PPHN), skin changes, arrhythmia, and persistent acidosis.
Outcome measures
| Measure |
High Dose Darbepoetin Alfa
n=10 Participants
10 mcg/kg/dose Darbe x2 doses, with the first dose within 12 hours of delivery and the second dose at 7 days
Darbepoetin alfa: 10 mcg/kg/dose x2, with the first dose given as IV within 12 hours of delivery and the second dose given as IV or SQ at 7 days old.
|
Low Dose Darbepoetin Alfa
n=10 Participants
2 mcg/kg/dose Darbe x2, with the first dose given within 12 hours of delivery and the second dose given at 7 days old.
Darbepoetin alfa: 2 mcg/kg/dose x2, with the first dose given IV within 12 hours of delivery and the second dose given IV or SQ at 7 days old.
|
Placebo
n=10 Participants
Placebo given x2 doses, with the first given within 12 hours of delivery and the second given at 7 days old
Placebo: Placebo given x2, with the first dose given IV within 12 hours of delivery and the second dose given IV or SQ at 7 days old
|
|---|---|---|---|
|
Number of Participants With Adverse Events.
|
7 participants
|
7 participants
|
8 participants
|
Adverse Events
High Dose Darbepoetin Alfa
Serious events: 0 serious events
Other events: 7 other events
Deaths: 0 deaths
Low Dose Darbepoetin Alfa
Serious events: 1 serious events
Other events: 7 other events
Deaths: 0 deaths
Placebo
Serious events: 1 serious events
Other events: 8 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
High Dose Darbepoetin Alfa
n=10 participants at risk
10 mcg/kg/dose Darbe x2 doses, with the first dose within 12 hours of delivery and the second dose at 7 days
Darbepoetin alfa: 10 mcg/kg/dose x2, with the first dose given as IV within 12 hours of delivery and the second dose given as IV or SQ at 7 days old.
|
Low Dose Darbepoetin Alfa
n=10 participants at risk
2 mcg/kg/dose Darbe x2, with the first dose given within 12 hours of delivery and the second dose given at 7 days old.
Darbepoetin alfa: 2 mcg/kg/dose x2, with the first dose given IV within 12 hours of delivery and the second dose given IV or SQ at 7 days old.
|
Placebo
n=10 participants at risk
Placebo given x2 doses, with the first given within 12 hours of delivery and the second given at 7 days old
Placebo: Placebo given x2, with the first dose given IV within 12 hours of delivery and the second dose given IV or SQ at 7 days old
|
|---|---|---|---|
|
General disorders
Death
|
0.00%
0/10
|
10.0%
1/10
|
10.0%
1/10
|
Other adverse events
| Measure |
High Dose Darbepoetin Alfa
n=10 participants at risk
10 mcg/kg/dose Darbe x2 doses, with the first dose within 12 hours of delivery and the second dose at 7 days
Darbepoetin alfa: 10 mcg/kg/dose x2, with the first dose given as IV within 12 hours of delivery and the second dose given as IV or SQ at 7 days old.
|
Low Dose Darbepoetin Alfa
n=10 participants at risk
2 mcg/kg/dose Darbe x2, with the first dose given within 12 hours of delivery and the second dose given at 7 days old.
Darbepoetin alfa: 2 mcg/kg/dose x2, with the first dose given IV within 12 hours of delivery and the second dose given IV or SQ at 7 days old.
|
Placebo
n=10 participants at risk
Placebo given x2 doses, with the first given within 12 hours of delivery and the second given at 7 days old
Placebo: Placebo given x2, with the first dose given IV within 12 hours of delivery and the second dose given IV or SQ at 7 days old
|
|---|---|---|---|
|
Cardiac disorders
Hypotension
|
40.0%
4/10
|
40.0%
4/10
|
40.0%
4/10
|
|
Cardiac disorders
Pulmonary Hypertension
|
20.0%
2/10
|
30.0%
3/10
|
10.0%
1/10
|
|
Hepatobiliary disorders
Altered Hepatic Function
|
20.0%
2/10
|
10.0%
1/10
|
10.0%
1/10
|
|
Renal and urinary disorders
Altered Renal Function
|
30.0%
3/10
|
60.0%
6/10
|
30.0%
3/10
|
|
Nervous system disorders
Seizures
|
30.0%
3/10
|
20.0%
2/10
|
0.00%
0/10
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place