Botulism
Conditions
Keywords
Pharmacokinetics, BAT, Pediatric
Brief summary
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.
Detailed description
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.
Interventions
BIOLOGICALBlood sample collection
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.
Sponsors
Emergent BioSolutions
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
1 Days to 11 Years
Healthy volunteers
No
Inclusion criteria
1. Legally authorized representative is able and willing to voluntarily provide informed consent and patients to provide assent, if applicable. 2. Pediatric participants (age groups: birth to \<two years, two to \<six years, and six to \<12 years). 3. Treatment with BAT product (initial dose only). 4. Blood sample can be collected (or standard of care sample scavenged) within 32 hours of completion of BAT product infusion.
Exclusion criteria
1. 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. 2. History of treatment with BabyBIG or other botulism antitoxin within the past 90 days.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Margin of PK Equivalence for 90% Survival | ideally up to 32 hours post-BAT product administration | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Area Under Concentration Curve From Time 0 to Last Measurable Concentration [AUC0-t] | ideally up to 32 hours post-BAT product administration | 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. |
| Area Under Concentration Curve From Time 0 to Infinity [AUC0-inf] | ideally up to 32 hours post-BAT product administration | 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. |
| Between Subject Variability [BSV] | ideally up to 32 hours post-BAT product administration | 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. |
| Maximum Serum Serotype A Concentration [Cmax] | ideally up to 32 hours post-BAT product administration | 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. |
| Systemic Clearance [CL] | ideally up to 32 hours post-BAT product administration | 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. |
| Intercompartmental Clearance [CLd] | ideally up to 32 hours post-BAT product administration | 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. |
| Central Volume of Distribution [Vc] | ideally up to 32 hours post-BAT product administration | 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. |
| Peripheral Volume of Distribution [Vp] | ideally up to 32 hours post-BAT product administration | 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. |
Contacts
STUDY_DIRECTORClinical Development Representative
Emergent BioSolutions
Outcome results
None listed