Trial Outcomes & Findings for Metronidazole Pharmacokinetics (PK) in Premature Infants (NCT NCT01222585)

NCT ID: NCT01222585

Last Updated: 2014-02-06

Results Overview

Area under the curve at steady state (AUCss)

• Recruitment status: COMPLETED
• Study phase: PHASE1
• Target enrollment: 24 participants
• Primary outcome timeframe: pre-dose: 30 min; post-dose:10 min, 3-4,6-8, 12-13, 24-25, 36-37, 48-49, 72-73 hours post dose
• Results posted on: 2014-02-06

Participant Flow

Participant milestones

Measure	Metronidazole IV Intravenous metronidazole loading dose 15 mg/kg followed by 7.5 mg/kg every 12-24 hours
Overall Study STARTED	24
Overall Study COMPLETED	24
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Metronidazole Pharmacokinetics (PK) in Premature Infants

Baseline characteristics by cohort

Measure	Treatment n=24 Participants Intravenous metronidazole loading dose 15 mg/kg followed by 7.5 mg/kg every 12-24 hours
Age, Continuous	25 weeks n=5 Participants
Sex: Female, Male Female	16 Participants n=5 Participants
Sex: Female, Male Male	8 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	6 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	18 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 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	1 Participants n=5 Participants
Race (NIH/OMB) Black or African American	7 Participants n=5 Participants
Race (NIH/OMB) White	16 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 United States	24 participants n=5 Participants
Birth Weight	740 grams n=5 Participants

PRIMARY outcome

Timeframe: pre-dose: 30 min; post-dose:10 min, 3-4,6-8, 12-13, 24-25, 36-37, 48-49, 72-73 hours post dose

Population: The PK analysis was conducted using samples from 23 subjects. One subject died soon after the loading dose and was excluded from the analysis. Two subjects had no multiple dose samples. Thus data from 20 subjects were used to estimate this PK parameter.

Area under the curve at steady state (AUCss)

Outcome measures

Measure	Metronidazole IV n=20 Participants Intravenous metronidazole loading dose 15 mg/kg followed by 7.5 mg/kg every 12-24 hours
Area Under the Curve at Steady State	178.0 mg*hr/L Interval 66.0 to 472.0

PRIMARY outcome

Timeframe: 2-5 days of study drug administration

Population: The sample size contains the number of subjects that had the sample of interest collected.

Loading Dose Maximum concentration (Cmax)

Outcome measures

Measure	Metronidazole IV n=19 Participants Intravenous metronidazole loading dose 15 mg/kg followed by 7.5 mg/kg every 12-24 hours
Loading Dose Maximum Concentration	16.54 mg/L Interval 9.18 to 19.63

PRIMARY outcome

Timeframe: 2-5 days of study drug administration

Population: The sample size contains the number of subjects that had the sample of interest collected.

Loading Dose Minimum Concentration (mg/L)

Outcome measures

Measure	Metronidazole IV n=17 Participants Intravenous metronidazole loading dose 15 mg/kg followed by 7.5 mg/kg every 12-24 hours
Loading Dose Minimum Concentration	9.20 mg/L Interval 3.21 to 12.82

PRIMARY outcome

Timeframe: 2-5 days of study drug administration

Population: The PK analysis was conducted using samples from 23 subjects. One subject died soon after the loading dose and was excluded from the analysis. Two subjects had no multiple dose samples. Thus data from 20 subjects were used to estimate the multiple dose PK parameter.

Multiple Dose Maximum Concentration (mg/L)

Outcome measures

Measure	Metronidazole IV n=20 Participants Intravenous metronidazole loading dose 15 mg/kg followed by 7.5 mg/kg every 12-24 hours
Multiple Dose Maximum Concentration	16.51 mg/L Interval 8.71 to 34.05

PRIMARY outcome

Timeframe: 2-5 days of study drug administration

Population: The sample size contains the number of subjects that had the sample of interest collected.

Multiple Dose Minimum Concentration (mg/L)

Outcome measures

Measure	Metronidazole IV n=21 Participants Intravenous metronidazole loading dose 15 mg/kg followed by 7.5 mg/kg every 12-24 hours
Multiple Dose Minimum Concentration	11.62 mg/L Interval 1.29 to 27.05

PRIMARY outcome

Timeframe: 2-5 days of study drug administration

Population: The PK analysis was conducted using samples from 23 subjects. One subject died soon after the loading dose and was excluded from the analysis. Two subjects had no multiple dose samples. Thus data from 20 subjects were used to estimate the PK parameter.

Clearance (L/h/kg)

Outcome measures

Measure	Metronidazole IV n=20 Participants Intravenous metronidazole loading dose 15 mg/kg followed by 7.5 mg/kg every 12-24 hours
Clearance	0.043 L/h/kg Interval 0.016 to 0.105

PRIMARY outcome

Timeframe: 2-5 days of study drug administration

Population: The PK analysis was conducted using samples from 23 subjects. One subject died soon after the loading dose and was excluded from the analysis. Two subjects had no multiple dose samples. Thus data from 20 subjects were used to estimate the PK parameter.

Volume of Distribution (L/kg)

Outcome measures

Measure	Metronidazole IV n=20 Participants Intravenous metronidazole loading dose 15 mg/kg followed by 7.5 mg/kg every 12-24 hours
Volume of Distribution	0.99 L/kg Interval 0.38 to 2.67

Adverse Events

Treatment

Serious events: 5 serious events

Other events: 17 other events

Deaths: 0 deaths

Serious adverse events

Measure	Treatment n=24 participants at risk Intravenous metronidazole loading dose 15 mg/kg followed by 7.5 mg/kg every 12-24 hours
General disorders Death	4.2% 1/24 • From first dose through 10 days post dose.
Cardiac disorders Cardiac arrest	4.2% 1/24 • From first dose through 10 days post dose.
Gastrointestinal disorders Necrotising colitis	8.3% 2/24 • From first dose through 10 days post dose.
Surgical and medical procedures Patent ductus arteriosus repair	4.2% 1/24 • From first dose through 10 days post dose.
Infections and infestations Septic shock	4.2% 1/24 • From first dose through 10 days post dose.
Renal and urinary disorders Renal failure acute	4.2% 1/24 • From first dose through 10 days post dose.

Other adverse events

Measure	Treatment n=24 participants at risk Intravenous metronidazole loading dose 15 mg/kg followed by 7.5 mg/kg every 12-24 hours
Endocrine disorders Endocrine disorders Adrenal Insufficiency	16.7% 4/24 • From first dose through 10 days post dose.
Nervous system disorders Convulsion	12.5% 3/24 • From first dose through 10 days post dose.
Skin and subcutaneous tissue disorders Dermatitis diaper	12.5% 3/24 • From first dose through 10 days post dose.
General disorders Other non-serious, infrequent adverse events	29.2% 7/24 • From first dose through 10 days post dose.

Additional Information

Michael Cohen-Wolkowiez, MD

Duke Clinical Research Institute

Phone: 919668-8812

Email: michael.cohenwolkowiez@dm.duke.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place