BT-011 Pharmacokinetics of Botulism Antitoxin Heptavalent in Pediatric Patients
Study Details
Study Description
Brief Summary
The purpose of this study is to verify the pediatric dosing recommendations for BAT® in pediatric patients that are treated with BAT® due to a confirmed or suspected case of botulism. A minimum of one serum sample should be collected but whenever feasible additional serum samples (up to three per enrolled subject) may be collected from the subject or obtained from surplus standard of care samples, if available, within 32 hours post BAT® administration.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 4 |
Detailed Description
Objectives: The purpose of this study is to collect serum from pediatric patients to analyze the pharmacokinetics (PK) of BAT® product to verify the currently approved pediatric dosing recommendations.
Protocol Design: This is a single arm, multi-site PK study in pediatric patients treated with BAT® product. The study begins once participation in the study is confirmed by the physician and informed consent/assent is obtained from the patient and/or legally authorized representative (LAR).
A minimum of one serum sample should be collected but whenever feasible additional serum samples (up to three per enrolled subject) may be collected from the subject or obtained from surplus standard of care samples, if available.
Assessments: At minimum, one 5 mL blood sample (to yield a minimum of 2 mL volume serum sample) will be collected after completion of BAT® product infusion. The collection of more than one sample, but not more than three samples per subject, is feasible only if:
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Pediatric subjects are >1 year old
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Pediatric subjects provided an early blood sample and a second sample can be collected later, but within the 32 hour collection time window
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If neonates are under close monitoring and require repeated blood sampling for standard of care; this would require coordination with the clinical care team for opportunistic PK sampling.
Pharmacokinetic Parameters: The serum concentrations of BAT product obtained will be modeled using a population PK approach based on a previously developed model for BAT serotypes A through G in healthy adult human subjects.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: A minimum of one 5 mL serum sample (up to three per enrolled subject) will be collected Intervention includes: A minimum of one 5 mL blood sample (up to three per enrolled subject) will be collected from pediatric patients treated with BAT® product. The blood sample should be collected no later than 32 hours post BAT® administration. To ensure sufficient detectable circulating levels of BAT® for pharmacokinetic analysis the target window of time for collection should be between 6 and 24 hours post-BAT® administration. |
Biological: A minimum of one 5 mL serum sample (up to three per enrolled subject) will be collected.
Intervention includes: A minimum of one 5 mL serum sample (up to three per enrolled subject) will be collected. The blood sample should be collected no later than 32 hours after completion of BAT product infusion. To ensure sufficient detectable circulating levels of BAT product for PK analysis the optimal target window of time for collection should be between 6- and 24-hours after completion of BAT product infusion.
|
Outcome Measures
Primary Outcome Measures
- Margin of Efficacy for 90% Survival [32 hours]
The serum concentrations of BAT product obtained will be modeled using a population PK approach based on a previously developed model for BAT serotypes A through G in healthy adult human subjects. The primary endpoint is the dosage level at which PK equivalence is reached relative to the healthy adult PK model. Following the estimation of exposure in pediatric patients, and similar to what was done for adult subjects, the margin of efficacy (MOE) for 90% survival will be estimated in order to verify the appropriateness of the administered pediatric dose.
Secondary Outcome Measures
- Area Under Concentration Curve From Time 0 to Last Measurable Concentration [AUC0-t] [32 hours]
Pharmacokinetic Parameters: Parameter estimates (area under the serum/plasma concentration curve from time 0 to the last measurable concentration [AUC0-t], area under the serum/plasma concentration curve from time 0 to infinity [AUC0-inf], between subject variability [BSV], maximum serum concentration [Cmax], systemic clearance [CL], intercompartmental clearance [CLd], central volume of distribution [Vc] and peripheral volume of distribution [Vp]) will be derived using the population PK model.
- Area Under Concentration Curve From Time 0 to Infinity [AUC0-inf] [32 Hours]
Pharmacokinetic Parameters: Parameter estimates (area under the serum/plasma concentration curve from time 0 to the last measurable concentration [AUC0-t], area under the serum/plasma concentration curve from time 0 to infinity [AUC0-inf], between subject variability [BSV], maximum serum concentration [Cmax], systemic clearance [CL], intercompartmental clearance [CLd], central volume of distribution [Vc] and peripheral volume of distribution [Vp]) will be derived using the population PK model.
- Area Under Concentration Curve From Time 0 to Between Subject Variability [BSV] [32 Hours]
Pharmacokinetic Parameters: Parameter estimates (area under the serum/plasma concentration curve from time 0 to the last measurable concentration [AUC0-t], area under the serum/plasma concentration curve from time 0 to infinity [AUC0-inf], between subject variability [BSV], maximum serum concentration [Cmax], systemic clearance [CL], intercompartmental clearance [CLd], central volume of distribution [Vc] and peripheral volume of distribution [Vp]) will be derived using the population PK model.
- Area Under Concentration Curve From Time 0 to Maximum Serum Concentration [Cmax] [32 Hours]
Pharmacokinetic Parameters: Parameter estimates (area under the serum/plasma concentration curve from time 0 to the last measurable concentration [AUC0-t], area under the serum/plasma concentration curve from time 0 to infinity [AUC0-inf], between subject variability [BSV], maximum serum concentration [Cmax], systemic clearance [CL], intercompartmental clearance [CLd], central volume of distribution [Vc] and peripheral volume of distribution [Vp]) will be derived using the population PK model.
- Area Under Concentration Curve From Time 0 to Systemic Clearance [CL] [32 Hours]
Pharmacokinetic Parameters: Parameter estimates (area under the serum/plasma concentration curve from time 0 to the last measurable concentration [AUC0-t], area under the serum/plasma concentration curve from time 0 to infinity [AUC0-inf], between subject variability [BSV], maximum serum concentration [Cmax], systemic clearance [CL], intercompartmental clearance [CLd], central volume of distribution [Vc] and peripheral volume of distribution [Vp]) will be derived using the population PK model.
- Area Under Concentration Curve From Time 0 to Intercompartmental Clearance [CLd] [32 Hours]
Pharmacokinetic Parameters: Parameter estimates (area under the serum/plasma concentration curve from time 0 to the last measurable concentration [AUC0-t], area under the serum/plasma concentration curve from time 0 to infinity [AUC0-inf], between subject variability [BSV], maximum serum concentration [Cmax], systemic clearance [CL], intercompartmental clearance [CLd], central volume of distribution [Vc] and peripheral volume of distribution [Vp]) will be derived using the population PK model.
- Area Under Concentration Curve From Time 0 to Central Volume of Distribution [Vc] [32 Hours]
Pharmacokinetic Parameters: Parameter estimates (area under the serum/plasma concentration curve from time 0 to the last measurable concentration [AUC0-t], area under the serum/plasma concentration curve from time 0 to infinity [AUC0-inf], between subject variability [BSV], maximum serum concentration [Cmax], systemic clearance [CL], intercompartmental clearance [CLd], central volume of distribution [Vc] and peripheral volume of distribution [Vp]) will be derived using the population PK model.
- Area Under Concentration Curve From Time 0 to Peripheral Volume of Distribution [Vp] [32 Hours]
Pharmacokinetic Parameters: Parameter estimates (area under the serum/plasma concentration curve from time 0 to the last measurable concentration [AUC0-t], area under the serum/plasma concentration curve from time 0 to infinity [AUC0-inf], between subject variability [BSV], maximum serum concentration [Cmax], systemic clearance [CL], intercompartmental clearance [CLd], central volume of distribution [Vc] and peripheral volume of distribution [Vp]) will be derived using the population PK model.
Eligibility Criteria
Criteria
Inclusion Criteria:
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Able and willing to provide informed consent (and assent as applicable) voluntarily signed by the subject and/or LAR.
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Pediatric patients [age category: pediatric - neonates (birth up to 1 month), infants (1 month up to 2 years), children (2 up to 12 years)].
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Treatment with BAT product.
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Blood sample can be collected (or standard of care sample scavenged) within 32 hours of completion of BAT product infusion.
Exclusion Criteria:
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If the 5 mL blood sample volume is deemed, at the discretion of the investigator, to be unsafe based on patient weight or condition of health.
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History of treatment with BabyBIG or other botulism antitoxin within the past 90 days.
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Emergent BioSolutions
- Biomedical Advanced Research and Development Authority
Investigators
- Study Director: Christine Hall, PhD, Emergent BioSolutions Inc
Study Documents (Full-Text)
None provided.More Information
Additional Information:
- Center for Disease Control and Prevention. Investigational heptavalent botulinum antitoxin to replace licensed botulinum antitoxin AB and investigational botulinum antitoxin E. Morbidity and Mortality Weekly Report. 2010;59(10):299.
- Guidance for industry and FDA staff. Best practices for conducting and reporting pharmacoepidemiologic safety studies using electronic health care data sets (draft guidance). United States Department of Health and Human
Publications
- Arnon SS, Schechter R, Inglesby TV, Henderson DA, Bartlett JG, Ascher MS, Eitzen E, Fine AD, Hauer J, Layton M, Lillibridge S, Osterholm MT, O'Toole T, Parker G, Perl TM, Russell PK, Swerdlow DL, Tonat K; Working Group on Civilian Biodefense. Botulinum toxin as a biological weapon: medical and public health management. JAMA. 2001 Feb 28;285(8):1059-70. Review. Erratum in: JAMA 2001 Apr 25;285(16):2081.
- Centers for Disease Control and Prevention (CDC). Investigational heptavalent botulinum antitoxin (HBAT) to replace licensed botulinum antitoxin AB and investigational botulinum antitoxin E. MMWR Morb Mortal Wkly Rep. 2010 Mar 19;59(10):299.
- Gangarosa EJ, Donadio JA, Armstrong RW, Meyer KF, Brachman PS, Dowell VR. Botulism in the United States, 1899-1969. Am J Epidemiol. 1971 Feb;93(2):93-101.
- Lack JA, Stuart-Taylor ME. Calculation of drug dosage and body surface area of children. Br J Anaesth. 1997 May;78(5):601-5. Erratum in: Br J Anaesth 1997 Aug;79(2):268.
- Richardson JS, Parrera GS, Astacio H, Sahota H, Anderson DM, Hall C, Babinchak T. Safety and Clinical Outcomes of an Equine-derived Heptavalent Botulinum Antitoxin Treatment for Confirmed or Suspected Botulism in the United States. Clin Infect Dis. 2020 Apr 15;70(9):1950-1957. doi: 10.1093/cid/ciz515.
- Shapiro RL, Hatheway C, Swerdlow DL. Botulism in the United States: a clinical and epidemiologic review. Ann Intern Med. 1998 Aug 1;129(3):221-8. Review.
- BT-011