Evaluation of the pharmacokinetics, safety, tolerability, and taste of tecovirimat pediatric formulations Not Applicable
Conditions
Interventions
Current interventions as of 06/10/2022:
In Part 1, subjects will receive each of the following treatments in a sequential manner:
Period 1, Regimen A-Tecovirimat Formulation Prototype 1 for Oral Susp
Sponsors
Siga Technologies (United States)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Healthy males and female subjects between 18 and 50 years of age, inclusive. 2. Female subjects of childbearing potential must not be pregnant, lactating, or planning to become pregnant before 3 months after the last dose of study drug, and have a negative urine pregnancy test at screening and admission. Female subjects of childbearing potential (including perimenopausal women who have had a menstrual bleeding within 1 year) must use appropriate birth control from 30 days before study drug administration until 35 days after last IMP administration. Women are considered to be not of childbearing potential if they have been surgically sterilized (documented hysterectomy or tubal ligation/occlusion) or are postmenopausal (had no menses for 12 months without an alternative medical cause and a serum follicle stimulating hormone [FSH] concentration =40 IU/L) 3. Male subjects must agree to not donate sperm from the first dose of study drug through 95 days after the last dose of study drug. 4. Subject has a body mass index between 18.0 and 32.0 kg/m2, inclusive, at screening 5. Subject is considered by the investigator to be in good general health as determined by medical history, clinical laboratory results, vital sign measurements, 12 lead electrocardiogram (ECG) results, and physical examination findings at screening 6. Subject agrees to comply with all protocol requirements 7. Subject is able to provide written informed consent
Exclusion criteria
Exclusion criteria: 1. Subject has received any vaccination within 28 days prior to Day 1 or plans to receive a vaccination at any time during the study until the follow-up phone call. 2. Subject has received treatment in another clinical study of an investigational drug (or medical device) within 90 days before the first dose of study drug. 3. Subjects who have previously been administered IMP in this study. Subjects who have taken part in Part 1 are not permitted to take part in Part 2. 4. Subject has any condition possibly affecting drug absorption (e.g., previous surgery on the gastrointestinal tract, including removal of parts of stomach, bowel, liver, gallbladder, or pancreas). 5. Subject has evidence or history of clinically significant allergies (except for untreated, asymptomatic, seasonal allergies at time of the first dose of study drug), haematological, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, renal, dermatological, or neurological disease. Exceptions to these criteria (e.g., stable, mild joint disease unassociated with collagen vascular disease) may be made following discussions with the medical monitor. 6. Subject reports lactose intolerance. 7. Subject has a history of cardiac disease, symptomatic or asymptomatic arrhythmias, syncopal episodes, or risk factors for torsades de pointes (e.g., heart failure, hypokalaemia). 8. Subject has a family history of sudden cardiac death not clearly due to acute myocardial infarction. 9. Subject has a seizure disorder or history of seizures (does not include childhood febrile seizures) or family history of idiopathic seizures. 10. Subject has a history of drug or alcohol abuse or dependency within the last 2 years before screening. 11. Regular alcohol consumption >14 units per week (1 unit = ½ pint beer, or a 25 mL shot of 40% spirit, 1.5 to 2 Units = 125 mL glass of wine, depending on type). 12. Subject has a current or recent (20 mg total dose per day) or high dose inhaled steroids (>800 mcg/day of beclomethasone dipropionate or equivalent) within the preceding 1 month. (Low dose [=800 µg/day of beclomethasone dipropionate or equivalent] inhaled and topical steroids are allowed). 16. Subject has donated >450 mL blood or blood components within 30 days before the first dose of study drug. The investigator should instruct subjects who participate in this study to not donate blood or blood components for 90 days following the last dose of study drug. 17. Subject is a smoker or has used nicotine or nicotine-containing products (e.g., cigarettes, electronic vapor cigarettes, cigars, chewing tobacco, snuff, nicotine patches, or nicotine gum) within 6 months before the first dose of study drug. 18. Subject has consumed grapefruit or grapefruit juice, pomegranate or pomegranate juice, pomelo fruits or pomelo juice, or alcohol-, caffeine-, or xanthine-containing products (e.g., tea, coffee, ch
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Current primary outcome measures as of 06/10/2022: Measurement of PK parameters of tecovirimat following administration of tecovirimat formulation prototype 1 for oral suspension, including but not limited to: Tmax, Cmax, C24, AUC (0-24), AUC(0-last), AUC(0-inf), Lambda-z, T1/2, CL/F and Vz/F measured using blood samples at timepoints 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36 and 48 hours after dosing _____ Previous primary outcome measures: PK parameters of tecovirimat measured using blood samples at pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36 and 48 hours after dosing: Tmax, Cmax, C24, AUC(0 24), AUC(0 last), AUC(0-inf), Lambda-z, T1/2, CL/F and Vz/F and Relative bioavailability (Frel) for Cmax, AUC(0-last) and AUC(0-inf) | — |
Secondary
| Measure | Time frame |
|---|---|
| Current secondary outcome measures as of 06/10/2022: 1. Taste attributes (smell, sweetness, bitterness, flavor, mouthfeel/texture, grittiness and aftertaste) and overall acceptability of the prototypes of the selected tecovirimat formulation for oral suspension measured using a 9-point scale at Part 1: Day 1 after investigational medicinal product (IMP) administration, Part 2: Day 1 and Day 8 after IMP administration 2. Adverse events (AEs), serious adverse events measured using case report forms at Parts 1 & 2: Day 1 after IMP administration through D7 post-dose 3. Comparison of the appropriate PK parameters of tecovirimat following administration of prototype 1 of the selected tecovirimat formulation for oral suspension including but not limited to: Tmax, Cmax, C24, AUC(0-24), AUC(0-last), AUC(0- inf), Lambda-z, T1/2, CL/F and Vz/F measured using blood samples on Day 1 and Day 8 4. Comparison of Cmax, AUC(0-last) and AUC(0-inf) following administration of the formulation prototype 1 of the tecovirimat formulation for oral suspension at 100 mg and 600 mg measured using blood samples at timepoints 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36 and 48 hours after dosing. _____ Previous primary outcome measures: 1. Taste attributes (smell, sweetness, bitterness, flavor, mouthfeel/texture, grittiness and aftertaste) and overall acceptability of the prototypes of the selected tecovirimat formulation for oral suspension measured using the taste questionnaire at Part 1: Day 1 after IMP administration, Part 2: Day 1 and Day 8 after IMP administration 2. Adverse events (AEs), serious adverse events measured using case report forms at Parts 1 & 2: Day 1 after IMP administration through D7 post dose 3. Clinical laboratory evaluations, (haematology, serum chemistry, urinalysis) at Parts 1 & 2: Screening, Pre-dose and 48 hrs. post dose (Discharge) 4. 12-lead ECGs measured at Part 1: Screening, Pre-dose; and 4,6,24, and 48 hrs, post dose (Discharge), Part 2: Screenin | — |
Countries
England, United Kingdom
Contacts
Public ContactEmily Blum
Outcome results
None listed