None listed
Conditions
Brief summary
This is a Phase 1 study to evaluate the effect of food on the PK of SION-719, and the bioequivalence of a solid oral formulation compared to the oral suspension.
Interventions
This is a Phase 1, open-label study designed to evaluate the effect of food on the pharmacokinetics (PK) of SION-719, and the bioequivalence of a solid oral formulation compared with oral suspension formulation in healthy participants.
This study will include a Screening Period, a Treatment Period, and an End of Study (EoS) phone call. Participants to be included in this study will be healthy male and female adults 18 to 55 years of age, inclusive, with no clinically significant concomitant med
This is a Phase 1, open-label study designed to evaluate the effect of food on the pharmacokinetics (PK) of SION-719, and the bioequivalence of a solid oral formulation compared with oral suspension formulation in healthy participants. This study will include a Screening Period, a Treatment Period, and an End of Study (EoS) phone call. Participants to be included in this study will be healthy male and female adults 18 to 55 years of age, inclusive, with no clinically significant concomitant medical conditions and who are not taking any concomitant medications. All potential participants will be screened a maximum of 28 days (Day -28) prior to check-in (Day -1) to assess their eligibility to enter the study and dosing will be initiated on Day 1, This study will be open label. Participants will be admitted to the Clinical Research Unit (CRU) on Day -1. On Day -1 or Day 1, each participant will be randomised to 1 of 3 open-label SION-719 treatment sequences (each consisting of 3 separate dose periods that will be given in a pre-specified order) and will receive the first dose of SION-719 in Period 1, dose to be determined (TBD); a dose will be selected at or below a dose that has been safe and well tolerated in the prior single ascending dose (SAD) study part (not exceeding 160 mg). Following a washout period of approximately 72 hours (actual duration will be determined prior to the start of this study, participants will receive the second dose of SION-719 in Period 2 of the sequence (Day 5). Following a washout period of approximately 72 hours (actual duration will be determined prior to the start of this study), participants will receive the third dose of SION-719 in Period 3 of the sequence (Day 9). The washout period between doses may be extended based on emerging PK data, in which case the day of dosing in Period 2 and Period 3 will be adjusted accordingly. Approximately 8 to 12 participants per cohort will be enrolled in this study. It may include up to 2 cohorts at 2 dose levels using doses equal to or less than doses that have been tested (in the prior SAD study) and found to be safe and well tolerated. In each dose period participants will receive one of the following treatments: Treatment I a single oral dose of SION-719 given as a tablet under fasted conditions. Treatment II a single oral dose of SION-719 given as a suspension under fasted conditions (as above) and Treatment III. a single oral dose of SION-719 given as a tablet dosed 30 minutes after the start of a high-fat meal. For the fasted dosing in Treatment I and II participants will be fasted for at least 10 hours pre-dose and 4 hours post-dose (if dose 1), or for 2 hours pre-dose and 2 hours post dose (if subsequent dose) depending on the treatment sequence. The contents of the high fat meal will be dependent on individual dietary restrictions, participants need to consume at least 75% of the high fat meal. As per the protocol, participants dosed in a fed state will follow FDA guidance of a standardised high fat meal (see the FDA Guidance for Industry; Assessing the Effect of Food on Drugs in INDs and NDAs – Clinical Pharmacology Considerations [June 2022]/, accessed online at https://www.fda.gov/media/121313/download). Participants will remain at the CRU for at least 72 hours following administration of their last dose (Day 9) for safety monitoring and collection of blood samples for PK analysis. The duration of participant follow up may be extended as the study proceeds if needed based on emerging PK data. All participants will be contacted by telephone for an EoS visit/Day 16 (+/- 1 day) after the last dose of study drug. Clinical facility staff will administer the study drug only to participants included in this study following the procedures set out in the study protocol. Administration of study drugs will be recorded in the appropriate drug accountability records. Each participant will be given only the study drug preparation carrying his/her study number.
Sponsors
Sionna Therapeutics, Inc
Study design
Allocation
Randomised controlled trial
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
1. Healthy male or female adult participants aged 18 to 55 years, inclusive, at the time of consent. 2. Weight of at least 45 kg and body mass index between 18.0 and 32.0 kg/m2, inclusive, at Screening. 3. Participant is willing to abstain from alcohol, caffeine, smoking, and nicotine-containing products for 72 hours prior to Day -1 through the duration of the study. Participant is willing to abstain from eating cruciferous vegetables, charcoal-grilled meats, and poppy seeds for 48 hours prior to dosing throughout the duration of the study. 4. Participant has read, understood, and voluntarily provided written informed consent. 5. Participant has an understanding, ability, and willingness to fully comply with study procedures and restrictions. 6. Female participants (sex assigned at birth) must be of non-childbearing potential or willing to comply with acceptable highly effective contraceptive requirements (including negative pregnancy tests). Male participants (sex assigned at birth) must be infertile or willing to comply with acceptable highly effective contraceptive requirements.
Exclusion criteria
1. Participant has clinically significant, in the opinion of the Investigator, current or recurrent illness, such as cardiovascular (including but not limited to known structural cardiac abnormalities, family history of long QT syndrome, or cardiac syncope or recurrent, idiopathic syncope), neurologic, pulmonary, hepatic, renal, metabolic, gastrointestinal, urologic, immunologic, endocrine, or psychiatric disease or disorder, or other abnormality which may affect safety or clinical laboratory evaluations. 2. Participant has a history of malignancy, except for basal cell or squamous epithelial carcinomas of the skin that have been resected with no evidence of recurrence for at least 1 year. 3. Participant has clinically significant abnormalities in the opinion of the Investigator, on ECG, physical examination, or vital sign assessment at Screening or Day -1. 4. Participant has any single reading of QTcF greater than 470ms (females) or greater than 450ms (males) at Screening or Day -1. 5. Chronic or habitual alcohol (more than 10 standard drinks per week) or tobacco (more than 10 cigarettes per week) use or use of recreational drugs (greater than 1 use per month). The Investigator may exclude a participant with lower levels of alcohol, tobacco or recreational drug use based on discretion and the pattern or history of use. 6. Participant is positive for drug screen at Screening or Day -1. Of note, the drug screen does not include cannabis, cotinine or alcohol testing at Screening but does include this testing at study Check-in (Day -1). 7. Participant has taken any prescription or over the counter medications within 14 days (or 5 half-lives of the medication, whichever is longer) prior to dosing or requires the use of these medications during the study, including herbal or homeopathic preparations excluding prophylactic doses of vitamin/mineral supplements and occasional paracetamol or ibuprofen, which are allowed. 8. Participant has clinically significant abnormalities, in the opinion of the Investigator, at Screening or Day -1 on safety laboratory tests including serum chemistry, haematology, coagulation (coagulation done at screening only) tests, and urinalysis. a. Participant must have an estimated glomerular filtration rate greater than 90 mL/min/1.73 m2 using the CKD-EPI 2021 formula and based on individual body surface area at Screening and Day -1. b. Participant must have ALT, AST, alkaline phosphatase, and direct bilirubin less than or equal to ULN at Screening and Day -1. 9. Participant has a positive test for hepatitis B surface antigen (HBsAg), hepatitis C antibody (HCV Ab), or human immunodeficiency virus antibody (HIV Ab) at Screening. Healthy volunteers who have no evidence of cirrhosis and have completed a curative intent regimen for HCV, with a negative HCV polymerase chain reaction (PCR) test, will not be excluded. 10. Participant has a positive test for Coronavirus Disease 2019 (COVID-19) at Day -1. 11. Participant has used any medication listed on the Flockhart table that is a substrate, inhibitor, or inducer of CYP3A4, or a substrate of CYP1A2 (with the exception of caffeine; see Inclusion Criterion 3), CYP2B6, CYP2C8, CYP2C19 or CYP2D6 within 28 days or 10 half-lives (whichever is longer) prior to the planned first study drug administration. Additionally, participants must not have consumed other substances known to be potent inhibitors or inducers of CYP450 such as Seville orange, grapefruit, or cranberry juice-containing products and herbal supplements such as St. John’s Wort within 14 days before the planned first study drug administration. 12. Participant has used any other prescription or over-the-counter medication that the Investigator judges is likely to interfere with the study or pose an additional risk in participating, within 14 days or 5 half-lives (whichever is longer) or has received any vaccinations within 14 days prior to the planned first study drug administration. 13. Participant has received an investigational product within 30 days or 5 half-lives (whichever is longer) of the first study drug administration or will start any other investigational product before the planned EoS Visit. 14. Participant has been treated with an investigational device within 30 days prior to first study drug administration or will start an investigational device study before the planned EoS Visit. 15. Participant has donated or lost greater than or equal to 400 mL blood (or plasma) within the last 6 weeks preceding the first study drug administration. 16. Participant has known or suspected intolerance or hypersensitivity to the investigational product, or any of the stated ingredients (including OraBlend® and hypromellose polymer). 17. Females who are breastfeeding or planning to breastfeed within 90 days of the EoS Visit. 18. Participant has an inability to follow a standardised meal schedule and diet or inability to fast, as required during the study.
Outcome results
None listed