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The purpose of this study is to verify the pediatric dosing recommendations for BAT product in pediatric patients that are treated with BAT product 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 participant) may be collected from the participant or obtained from surplus standard of care samples, if available, within 32 hours after BAT product administration. Safety of the BAT product will also be evaluated. Emergent will follow-up with the physician by telephone after 30 days post-BAT product administration to collect AEs, SAEs, and unanticipated events.
Primary Objective: To collect blood from pediatric participants to analyze the pharmacokinetics (PK) of BAT product to verify the current US FDA-approved pediatric dosing recommendations for BAT product.
Safety Objective: To evaluate the safety of BAT product in pediatric participants.
Protocol Design: This is a single arm, multi-site PK study in pediatric patients treated with BAT product.
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 participants.
Safety Endpoints: The incidence of adverse events (AEs), serious adverse events (SAEs), and adverse events of special interest (AESI) that occur within 30 days after BAT product administration. In this study hypersensitivity/allergic reactions including serum sickness, febrile reactions, and hemodynamic instability and bradycardia, as well as reports of an infectious disease transmission will be included as AESI.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Blood sample collection | Experimental | One to three 5 mL blood samples will be collected from pediatric participants treated with BAT product ideally 6-24 hours after administration, but within a maximum of 32 hours after administration. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Blood sample collection | Biological | One to three 5 mL blood samples will be collected from pediatric participants treated with BAT product ideally 6-24 hours after administration but within a maximum of 32 hours after administration. |
| Measure | Description | Time Frame |
|---|---|---|
| Margin of PK Equivalence for 90% Survival | Margin of PK equivalence (MOE) for 90% survival relative to the healthy adult PK model, calculated to verify the appropriateness of administered pediatric dose. All collected samples of sufficient volume will be used provided both the BAT dosing time and sample collection time are known, even if outside the 32 hour collection window. | ideally up to 32 hours post-BAT product administration |
| Measure | Description | Time Frame |
|---|---|---|
| Area Under Concentration Curve From Time 0 to Last Measurable Concentration [AUC0-t] | Pharmacokinetic Parameter: Estimated area under the serum concentration-time curve from time 0 to the last measurable serotype A concentration [AUC0-t]. All collected samples of sufficient volume will be used provided both the BAT dosing time and sample collection time are known, even if outside the 32 hour collection window. |
| Measure | Description | Time Frame |
|---|---|---|
| Safety: AEs | Number of AEs that occur within 30 days after BAT product administration | Day 1 to Day 30 |
| Safety: SAEs | Number of SAEs that occur within 30 days after BAT product administration |
Inclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Clinical Development Representative | Emergent BioSolutions | Study Director |
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| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 31209461 | Background | 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. | |
| 35050996 | Background |
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| ID | Term |
|---|---|
| D001906 | Botulism |
| ID | Term |
|---|---|
| D003015 | Clostridium Infections |
| D016908 | Gram-Positive Bacterial Infections |
| D001424 | Bacterial Infections |
| D001423 | Bacterial Infections and Mycoses |
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| ideally up to 32 hours post-BAT product administration |
| Area Under Concentration Curve From Time 0 to Infinity [AUC0-inf] | Pharmacokinetic Parameter: Estimated area under the serum concentration-time curve from time 0 to infinity [AUC0-inf]. All collected samples of sufficient volume will be used provided both the BAT dosing time and sample collection time are known, even if outside the 32 hour collection window. | ideally up to 32 hours post-BAT product administration |
| Between Subject Variability [BSV] | Pharmacokinetic Parameter: Between subject variability [BSV]. All collected samples of sufficient volume will be used provided both the BAT dosing time and sample collection time are known, even if outside the 32 hour collection window. | ideally up to 32 hours post-BAT product administration |
| Maximum Serum Serotype A Concentration [Cmax] | Pharmacokinetic Parameters: Estimated maximum serum serotype A concentration [Cmax]. All collected samples of sufficient volume will be used provided both the BAT dosing time and sample collection time are known, even if outside the 32 hour collection window. | ideally up to 32 hours post-BAT product administration |
| Systemic Clearance [CL] | Pharmacokinetic Parameters: Estimated systemic clearance [CL]. All collected samples of sufficient volume will be used provided both the BAT dosing time and sample collection time are known, even if outside the 32 hour collection window. | ideally up to 32 hours post-BAT product administration |
| Intercompartmental Clearance [CLd] | Pharmacokinetic Parameters: Estimated intercompartmental clearance [CLd]. All collected samples of sufficient volume will be used provided both the BAT dosing time and sample collection time are known, even if outside the 32 hour collection window. | ideally up to 32 hours post-BAT product administration |
| Central Volume of Distribution [Vc] | Pharmacokinetic Parameters: Estimated central volume of distribution [Vc]. All collected samples of sufficient volume will be used provided both the BAT dosing time and sample collection time are known, even if outside the 32 hour collection window. | ideally up to 32 hours post-BAT product administration |
| Peripheral Volume of Distribution [Vp] | Pharmacokinetic Parameters: Estimated peripheral volume of distribution [Vp]). All collected samples of sufficient volume will be used provided both the BAT dosing time and sample collection time are known, even if outside the 32 hour collection window. | ideally up to 32 hours post-BAT product administration |
| Day 1 to Day 30 |
| Safety: AESI | Number of AESI that occur within 30 days after BAT product administration | Day 1 to Day 30 |
| Parrera GS, Astacio H, Tunga P, Anderson DM, Hall CL, Richardson JS. Use of Botulism Antitoxin Heptavalent (A, B, C, D, E, F, G)-(Equine) (BAT(R)) in Clinical Study Subjects and Patients: A 15-Year Systematic Safety Review. Toxins (Basel). 2021 Dec 27;14(1):19. doi: 10.3390/toxins14010019. |
| 35467014 | Background | Beliveau M, Anderson D, Barker D, Kodihalli S, Simard E, Hall C, Richardson JS. Exposure-Response Modeling and Simulation to Support Human Dosing of Botulism Antitoxin Heptavalent Product. Clin Pharmacol Ther. 2022 Jul;112(1):171-180. doi: 10.1002/cpt.2620. Epub 2022 May 16. |
| 33956777 | Background | Rao AK, Sobel J, Chatham-Stephens K, Luquez C. Clinical Guidelines for Diagnosis and Treatment of Botulism, 2021. MMWR Recomm Rep. 2021 May 7;70(2):1-30. doi: 10.15585/mmwr.rr7002a1. |
| D007239 | Infections |
| D020511 | Neuromuscular Junction Diseases |
| D009468 | Neuromuscular Diseases |
| D009422 | Nervous System Diseases |
| D020258 | Neurotoxicity Syndromes |
| D005517 | Foodborne Diseases |
| D011041 | Poisoning |
| D064419 | Chemically-Induced Disorders |