Trial Outcomes & Findings for Pharmacokinetic and Safety Study of HYLENEX Recombinant-Augmented Subcutaneous Ceftriaxone Administration (NCT NCT00493220)

NCT ID: NCT00493220

Last Updated: 2011-12-02

Results Overview

Area under the drug concentration-time curve from time zero to the time of the last measurable concentration (calculated by the linear trapezoidal method)

• Recruitment status: COMPLETED
• Study phase: PHASE1
• Target enrollment: 30 participants
• Primary outcome timeframe: Start of ceftriaxone administration through time of last measureable plasma ceftriaxone concentration
• Results posted on: 2011-12-02

Participant Flow

Healthy volunteers recruited via subject-initiated telephone or internet contacts or visits to Phase I unit. Those considered potentially eligible were, after obtaining consent, screened in detail to determine eligibility against protocol eligibility criteria.

Participant milestones

Measure	HYLENEX SC, Placebo SC, IV subcutaneous HYLENEX and ceftriaxone as first intervention, subcutaneous placebo and ceftriaxone as second intervention, intravenous ceftriaxone as third intervention	HYLENEX SC, IV, Placebo SC subcutaneous HYLENEX and ceftriaxone as first intervention, intravenous ceftriaxone as second intervention, subcutaneous placebo and ceftriaxone as third intervention	Placebo SC, HYLENEX SC, IV subcutaneous placebo and ceftriaxone as first intervention, subcutaneous HYLENEX and ceftriaxone as second intervention, intravenous ceftriaxone as third intervention	Placebo SC, IV, HYLENEX SC subcutaneous placebo and ceftriaxone as first intervention, intravenous ceftriaxone as second intervention, subcutaneous HYLENEX and ceftriaxone as third intervention	IV, HYLENEX SC, Placebo SC intravenous ceftriaxone as first intervention, subcutaneous HYLENEX and ceftriaxone as second intervention, subcutaneous placebo and ceftriaxone as third intervention	IV, Placebo SC, HYLENEX SC intravenous ceftriaxone as first intervention, subcutaneous placebo and ceftriaxone as second intervention, subcutaneous HYLENEX and ceftriaxone as third intervention
First Intervention STARTED	5	5	5	5	5	5
First Intervention COMPLETED	5	5	5	5	5	5
First Intervention NOT COMPLETED	0	0	0	0	0	0
First 7-Day Washout & Safety Follow-up STARTED	5	5	5	5	5	5
First 7-Day Washout & Safety Follow-up COMPLETED	5	5	5	5	5	5
First 7-Day Washout & Safety Follow-up NOT COMPLETED	0	0	0	0	0	0
Second Intervention STARTED	5	5	5	5	5	5
Second Intervention COMPLETED	5	5	5	5	5	5
Second Intervention NOT COMPLETED	0	0	0	0	0	0
Second 7-Day Washout & Safety Follow-up STARTED	5	5	5	5	5	5
Second 7-Day Washout & Safety Follow-up COMPLETED	5	5	5	5	5	5
Second 7-Day Washout & Safety Follow-up NOT COMPLETED	0	0	0	0	0	0
Third Intervention STARTED	5	5	5	5	5	5
Third Intervention COMPLETED	4	5	5	5	5	5
Third Intervention NOT COMPLETED	1	0	0	0	0	0
Final 7-Day Safety Follow-up STARTED	4	5	5	5	5	5
Final 7-Day Safety Follow-up COMPLETED	4	5	5	5	5	5
Final 7-Day Safety Follow-up NOT COMPLETED	0	0	0	0	0	0

Reasons for withdrawal

Measure	HYLENEX SC, Placebo SC, IV subcutaneous HYLENEX and ceftriaxone as first intervention, subcutaneous placebo and ceftriaxone as second intervention, intravenous ceftriaxone as third intervention	HYLENEX SC, IV, Placebo SC subcutaneous HYLENEX and ceftriaxone as first intervention, intravenous ceftriaxone as second intervention, subcutaneous placebo and ceftriaxone as third intervention	Placebo SC, HYLENEX SC, IV subcutaneous placebo and ceftriaxone as first intervention, subcutaneous HYLENEX and ceftriaxone as second intervention, intravenous ceftriaxone as third intervention	Placebo SC, IV, HYLENEX SC subcutaneous placebo and ceftriaxone as first intervention, intravenous ceftriaxone as second intervention, subcutaneous HYLENEX and ceftriaxone as third intervention	IV, HYLENEX SC, Placebo SC intravenous ceftriaxone as first intervention, subcutaneous HYLENEX and ceftriaxone as second intervention, subcutaneous placebo and ceftriaxone as third intervention	IV, Placebo SC, HYLENEX SC intravenous ceftriaxone as first intervention, subcutaneous placebo and ceftriaxone as second intervention, subcutaneous HYLENEX and ceftriaxone as third intervention
Third Intervention Withdrawal by Subject	1	0	0	0	0	0

Baseline Characteristics

Pharmacokinetic and Safety Study of HYLENEX Recombinant-Augmented Subcutaneous Ceftriaxone Administration

Baseline characteristics by cohort

Measure	HYLENEX SC, Placebo SC, IV n=5 Participants subcutaneous HYLENEX and ceftriaxone as first intervention, subcutaneous placebo and ceftriaxone as second intervention, intravenous ceftriaxone as third intervention	HYLENEX SC, IV, Placebo SC n=5 Participants subcutaneous HYLENEX and ceftriaxone as first intervention, intravenous ceftriaxone as second intervention, subcutaneous placebo and ceftriaxone as third intervention	Placebo SC, HYLENEX SC, IV n=5 Participants subcutaneous placebo and ceftriaxone as first intervention, subcutaneous HYLENEX and ceftriaxone as second intervention, intravenous ceftriaxone as third intervention	Placebo SC, IV, HYLENEX SC n=5 Participants subcutaneous placebo and ceftriaxone as first intervention, intravenous ceftriaxone as second intervention, subcutaneous HYLENEX and ceftriaxone as third intervention	IV, HYLENEX SC, Placebo SC n=5 Participants intravenous ceftriaxone as first intervention, subcutaneous HYLENEX and ceftriaxone as second intervention, subcutaneous placebo and ceftriaxone as third intervention	IV, Placebo SC, HYLENEX SC n=5 Participants intravenous ceftriaxone as first intervention, subcutaneous placebo and ceftriaxone as second intervention, subcutaneous HYLENEX and ceftriaxone as third intervention	Total n=30 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants	0 Participants n=36 Participants	0 Participants n=10 Participants	0 Participants n=115 Participants
Age, Categorical Between 18 and 65 years	5 Participants n=93 Participants	5 Participants n=4 Participants	5 Participants n=27 Participants	5 Participants n=483 Participants	5 Participants n=36 Participants	5 Participants n=10 Participants	30 Participants n=115 Participants
Age, Categorical >=65 years	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants	0 Participants n=36 Participants	0 Participants n=10 Participants	0 Participants n=115 Participants
Age Continuous	32.2 years STANDARD_DEVIATION 10.6 • n=93 Participants	37.6 years STANDARD_DEVIATION 4.0 • n=4 Participants	34.2 years STANDARD_DEVIATION 11.5 • n=27 Participants	34.8 years STANDARD_DEVIATION 17.5 • n=483 Participants	34.8 years STANDARD_DEVIATION 11.0 • n=36 Participants	33.2 years STANDARD_DEVIATION 8.0 • n=10 Participants	34.5 years STANDARD_DEVIATION 10.3 • n=115 Participants
Sex: Female, Male Female	1 Participants n=93 Participants	0 Participants n=4 Participants	1 Participants n=27 Participants	1 Participants n=483 Participants	2 Participants n=36 Participants	0 Participants n=10 Participants	5 Participants n=115 Participants
Sex: Female, Male Male	4 Participants n=93 Participants	5 Participants n=4 Participants	4 Participants n=27 Participants	4 Participants n=483 Participants	3 Participants n=36 Participants	5 Participants n=10 Participants	25 Participants n=115 Participants
Region of Enrollment United States	5 participants n=93 Participants	5 participants n=4 Participants	5 participants n=27 Participants	5 participants n=483 Participants	5 participants n=36 Participants	5 participants n=10 Participants	30 participants n=115 Participants

PRIMARY outcome

Timeframe: Start of ceftriaxone administration through time of last measureable plasma ceftriaxone concentration

Population: Per protocol (excludes one participant that did not receive intravenous ceftriaxone intervention)

Area under the drug concentration-time curve from time zero to the time of the last measurable concentration (calculated by the linear trapezoidal method)

Outcome measures

Measure	HYLENEX SC n=29 Participants All per-protocol participants administered subcutaneous hylenex and ceftriaxone	Placebo SC n=29 Participants All per-protocol participants administered subcutaneous placebo and ceftriaxone	Intravenous n=29 Participants All per-protocol participants administered intravenous ceftriaxone
AUC0-t	1139.3 μg*hr/mL Standard Deviation 200.30	1115.6 μg*hr/mL Standard Deviation 180.55	1065.3 μg*hr/mL Standard Deviation 176.07

PRIMARY outcome

Timeframe: from the start of ceftriaxone administration to infinity

Population: Per protocol (excludes one participant that did not receive intravenous ceftriaxone intervention)

Area under the drug concentration-time curve from time zero to infinity, calculated as AUC0-t + Ct/kel (Ct = time of last measurable concentration; kel = terminal elimination rate constant)

Outcome measures

Measure	HYLENEX SC n=29 Participants All per-protocol participants administered subcutaneous hylenex and ceftriaxone	Placebo SC n=29 Participants All per-protocol participants administered subcutaneous placebo and ceftriaxone	Intravenous n=29 Participants All per-protocol participants administered intravenous ceftriaxone
AUC0-inf	1162.6 µg*hr/mL Standard Deviation 210.36	1141.3 µg*hr/mL Standard Deviation 192.86	1085.8 µg*hr/mL Standard Deviation 187.50

SECONDARY outcome

Timeframe: at the time of the highest measured plasma ceftriaxone concentration

Population: Per protocol (excludes one participant that did not receive intravenous ceftriaxone intervention)

Maximum measured plasma ceftriaxone concentration

Outcome measures

Measure	HYLENEX SC n=29 Participants All per-protocol participants administered subcutaneous hylenex and ceftriaxone	Placebo SC n=29 Participants All per-protocol participants administered subcutaneous placebo and ceftriaxone	Intravenous n=29 Participants All per-protocol participants administered intravenous ceftriaxone
Cmax	92.0 µg/mL Standard Deviation 15.1	82.2 µg/mL Standard Deviation 13.5	150 µg/mL Standard Deviation 19.9

SECONDARY outcome

Timeframe: from start of ceftriaxone administration until time of maximum measured plasma ceftriaxone concentration

Population: Per protocol (excludes one participant that did not receive intravenous ceftriaxone intervention)

Time to maximum measured plasma ceftriaxone concentration

Outcome measures

Measure	HYLENEX SC n=29 Participants All per-protocol participants administered subcutaneous hylenex and ceftriaxone	Placebo SC n=29 Participants All per-protocol participants administered subcutaneous placebo and ceftriaxone	Intravenous n=29 Participants All per-protocol participants administered intravenous ceftriaxone
Tmax	2.02 hr Interval 1.02 to 3.01	3.02 hr Interval 1.52 to 4.04	0.502 hr Interval 0.501 to 0.611

Adverse Events

HYLENEX SC

Serious events: 0 serious events

Other events: 30 other events

Deaths: 0 deaths

Placebo SC

Serious events: 0 serious events

Other events: 30 other events

Deaths: 0 deaths

Intravenous

Serious events: 0 serious events

Other events: 22 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	HYLENEX SC n=30 participants at risk All participants administered subcutaneous HYLENEX and ceftriaxone	Placebo SC n=30 participants at risk All participants administered subcutaneous placebo and ceftriaxone	Intravenous n=29 participants at risk All participants administered intravenous ceftriaxone
General disorders Infusion site anaesthesia	13.3% 4/30 • from time of start of intervention administration through 7 days after intervention administered Infusion site reaction assessments performed at baseline (shortly before study drug administration) and at 5, 30 and 45 minutes, and 1, 4, 6, 24, 36 and 48 hours after completion of study drug administration. Other adverse events were to be recorded whenever reported by the participant or observed by study staff.	3.3% 1/30 • from time of start of intervention administration through 7 days after intervention administered Infusion site reaction assessments performed at baseline (shortly before study drug administration) and at 5, 30 and 45 minutes, and 1, 4, 6, 24, 36 and 48 hours after completion of study drug administration. Other adverse events were to be recorded whenever reported by the participant or observed by study staff.	0.00% 0/29 • from time of start of intervention administration through 7 days after intervention administered Infusion site reaction assessments performed at baseline (shortly before study drug administration) and at 5, 30 and 45 minutes, and 1, 4, 6, 24, 36 and 48 hours after completion of study drug administration. Other adverse events were to be recorded whenever reported by the participant or observed by study staff.
General disorders Infusion site bruising	6.7% 2/30 • from time of start of intervention administration through 7 days after intervention administered Infusion site reaction assessments performed at baseline (shortly before study drug administration) and at 5, 30 and 45 minutes, and 1, 4, 6, 24, 36 and 48 hours after completion of study drug administration. Other adverse events were to be recorded whenever reported by the participant or observed by study staff.	13.3% 4/30 • from time of start of intervention administration through 7 days after intervention administered Infusion site reaction assessments performed at baseline (shortly before study drug administration) and at 5, 30 and 45 minutes, and 1, 4, 6, 24, 36 and 48 hours after completion of study drug administration. Other adverse events were to be recorded whenever reported by the participant or observed by study staff.	20.7% 6/29 • from time of start of intervention administration through 7 days after intervention administered Infusion site reaction assessments performed at baseline (shortly before study drug administration) and at 5, 30 and 45 minutes, and 1, 4, 6, 24, 36 and 48 hours after completion of study drug administration. Other adverse events were to be recorded whenever reported by the participant or observed by study staff.
General disorders Infusion site erythema	60.0% 18/30 • from time of start of intervention administration through 7 days after intervention administered Infusion site reaction assessments performed at baseline (shortly before study drug administration) and at 5, 30 and 45 minutes, and 1, 4, 6, 24, 36 and 48 hours after completion of study drug administration. Other adverse events were to be recorded whenever reported by the participant or observed by study staff.	50.0% 15/30 • from time of start of intervention administration through 7 days after intervention administered Infusion site reaction assessments performed at baseline (shortly before study drug administration) and at 5, 30 and 45 minutes, and 1, 4, 6, 24, 36 and 48 hours after completion of study drug administration. Other adverse events were to be recorded whenever reported by the participant or observed by study staff.	13.8% 4/29 • from time of start of intervention administration through 7 days after intervention administered Infusion site reaction assessments performed at baseline (shortly before study drug administration) and at 5, 30 and 45 minutes, and 1, 4, 6, 24, 36 and 48 hours after completion of study drug administration. Other adverse events were to be recorded whenever reported by the participant or observed by study staff.
General disorders Infusion site induration	6.7% 2/30 • from time of start of intervention administration through 7 days after intervention administered Infusion site reaction assessments performed at baseline (shortly before study drug administration) and at 5, 30 and 45 minutes, and 1, 4, 6, 24, 36 and 48 hours after completion of study drug administration. Other adverse events were to be recorded whenever reported by the participant or observed by study staff.	3.3% 1/30 • from time of start of intervention administration through 7 days after intervention administered Infusion site reaction assessments performed at baseline (shortly before study drug administration) and at 5, 30 and 45 minutes, and 1, 4, 6, 24, 36 and 48 hours after completion of study drug administration. Other adverse events were to be recorded whenever reported by the participant or observed by study staff.	0.00% 0/29 • from time of start of intervention administration through 7 days after intervention administered Infusion site reaction assessments performed at baseline (shortly before study drug administration) and at 5, 30 and 45 minutes, and 1, 4, 6, 24, 36 and 48 hours after completion of study drug administration. Other adverse events were to be recorded whenever reported by the participant or observed by study staff.
General disorders Infusion site pain	100.0% 30/30 • from time of start of intervention administration through 7 days after intervention administered Infusion site reaction assessments performed at baseline (shortly before study drug administration) and at 5, 30 and 45 minutes, and 1, 4, 6, 24, 36 and 48 hours after completion of study drug administration. Other adverse events were to be recorded whenever reported by the participant or observed by study staff.	100.0% 30/30 • from time of start of intervention administration through 7 days after intervention administered Infusion site reaction assessments performed at baseline (shortly before study drug administration) and at 5, 30 and 45 minutes, and 1, 4, 6, 24, 36 and 48 hours after completion of study drug administration. Other adverse events were to be recorded whenever reported by the participant or observed by study staff.	31.0% 9/29 • from time of start of intervention administration through 7 days after intervention administered Infusion site reaction assessments performed at baseline (shortly before study drug administration) and at 5, 30 and 45 minutes, and 1, 4, 6, 24, 36 and 48 hours after completion of study drug administration. Other adverse events were to be recorded whenever reported by the participant or observed by study staff.
General disorders Infusion site pruritus	6.7% 2/30 • from time of start of intervention administration through 7 days after intervention administered Infusion site reaction assessments performed at baseline (shortly before study drug administration) and at 5, 30 and 45 minutes, and 1, 4, 6, 24, 36 and 48 hours after completion of study drug administration. Other adverse events were to be recorded whenever reported by the participant or observed by study staff.	0.00% 0/30 • from time of start of intervention administration through 7 days after intervention administered Infusion site reaction assessments performed at baseline (shortly before study drug administration) and at 5, 30 and 45 minutes, and 1, 4, 6, 24, 36 and 48 hours after completion of study drug administration. Other adverse events were to be recorded whenever reported by the participant or observed by study staff.	6.9% 2/29 • from time of start of intervention administration through 7 days after intervention administered Infusion site reaction assessments performed at baseline (shortly before study drug administration) and at 5, 30 and 45 minutes, and 1, 4, 6, 24, 36 and 48 hours after completion of study drug administration. Other adverse events were to be recorded whenever reported by the participant or observed by study staff.
General disorders Infusion site reaction	20.0% 6/30 • from time of start of intervention administration through 7 days after intervention administered Infusion site reaction assessments performed at baseline (shortly before study drug administration) and at 5, 30 and 45 minutes, and 1, 4, 6, 24, 36 and 48 hours after completion of study drug administration. Other adverse events were to be recorded whenever reported by the participant or observed by study staff.	0.00% 0/30 • from time of start of intervention administration through 7 days after intervention administered Infusion site reaction assessments performed at baseline (shortly before study drug administration) and at 5, 30 and 45 minutes, and 1, 4, 6, 24, 36 and 48 hours after completion of study drug administration. Other adverse events were to be recorded whenever reported by the participant or observed by study staff.	0.00% 0/29 • from time of start of intervention administration through 7 days after intervention administered Infusion site reaction assessments performed at baseline (shortly before study drug administration) and at 5, 30 and 45 minutes, and 1, 4, 6, 24, 36 and 48 hours after completion of study drug administration. Other adverse events were to be recorded whenever reported by the participant or observed by study staff.
General disorders Infusion site swelling	16.7% 5/30 • from time of start of intervention administration through 7 days after intervention administered Infusion site reaction assessments performed at baseline (shortly before study drug administration) and at 5, 30 and 45 minutes, and 1, 4, 6, 24, 36 and 48 hours after completion of study drug administration. Other adverse events were to be recorded whenever reported by the participant or observed by study staff.	93.3% 28/30 • from time of start of intervention administration through 7 days after intervention administered Infusion site reaction assessments performed at baseline (shortly before study drug administration) and at 5, 30 and 45 minutes, and 1, 4, 6, 24, 36 and 48 hours after completion of study drug administration. Other adverse events were to be recorded whenever reported by the participant or observed by study staff.	3.4% 1/29 • from time of start of intervention administration through 7 days after intervention administered Infusion site reaction assessments performed at baseline (shortly before study drug administration) and at 5, 30 and 45 minutes, and 1, 4, 6, 24, 36 and 48 hours after completion of study drug administration. Other adverse events were to be recorded whenever reported by the participant or observed by study staff.
General disorders Vessel puncture site bruise	3.3% 1/30 • from time of start of intervention administration through 7 days after intervention administered Infusion site reaction assessments performed at baseline (shortly before study drug administration) and at 5, 30 and 45 minutes, and 1, 4, 6, 24, 36 and 48 hours after completion of study drug administration. Other adverse events were to be recorded whenever reported by the participant or observed by study staff.	6.7% 2/30 • from time of start of intervention administration through 7 days after intervention administered Infusion site reaction assessments performed at baseline (shortly before study drug administration) and at 5, 30 and 45 minutes, and 1, 4, 6, 24, 36 and 48 hours after completion of study drug administration. Other adverse events were to be recorded whenever reported by the participant or observed by study staff.	6.9% 2/29 • from time of start of intervention administration through 7 days after intervention administered Infusion site reaction assessments performed at baseline (shortly before study drug administration) and at 5, 30 and 45 minutes, and 1, 4, 6, 24, 36 and 48 hours after completion of study drug administration. Other adverse events were to be recorded whenever reported by the participant or observed by study staff.
Nervous system disorders Headache	6.7% 2/30 • from time of start of intervention administration through 7 days after intervention administered Infusion site reaction assessments performed at baseline (shortly before study drug administration) and at 5, 30 and 45 minutes, and 1, 4, 6, 24, 36 and 48 hours after completion of study drug administration. Other adverse events were to be recorded whenever reported by the participant or observed by study staff.	10.0% 3/30 • from time of start of intervention administration through 7 days after intervention administered Infusion site reaction assessments performed at baseline (shortly before study drug administration) and at 5, 30 and 45 minutes, and 1, 4, 6, 24, 36 and 48 hours after completion of study drug administration. Other adverse events were to be recorded whenever reported by the participant or observed by study staff.	0.00% 0/29 • from time of start of intervention administration through 7 days after intervention administered Infusion site reaction assessments performed at baseline (shortly before study drug administration) and at 5, 30 and 45 minutes, and 1, 4, 6, 24, 36 and 48 hours after completion of study drug administration. Other adverse events were to be recorded whenever reported by the participant or observed by study staff.

Additional Information

George Harb, MD, MPH

Baxter Healthcare Corporation

Email: george_harb@baxter.com

Results disclosure agreements

• Principal investigator is a sponsor employee For this study, Baxter requires a review of any planned PI results communications (eg, for confidential information) up to 90 days prior to submission or communication. Baxter may request an additional delay of up to 60 days (eg, to allow for intellectual property protection).
• Publication restrictions are in place

Restriction type: OTHER