Cystic Fibrosis (CF)
Conditions
Brief summary
The purpose of Parts D and E of this Phase 1 study are to evaluate the safety, tolerability, and pharmacokinetics of multiple dose combinations of SION-451 and complementary modulators SION-2222 and SION-109 in healthy participants.
Detailed description
This is a Phase 1 randomized, double-blind, placebo-controlled study. Parts D and E will evaluate the safety, tolerability, and pharmacokinetics of multiple dose combinations of SION-451 and complementary modulators SION-2222 and SION-109 in healthy participants. Parts A, B, and C of this study have completed dosing. Part D will involve multiple dosing of SION-451 and SION-2222 in combination. Part E will involve multiple dosing of SION-451 and SION-109 in combination.
Interventions
DRUGSION-451
* Pharmaceutical form: tablet * Route of administration: oral
DRUGSION-2222
* Pharmaceutical form: capsule * Route of administration: oral
DRUGSION-109
* Pharmaceutical form: tablet * Route of administration: oral
DRUGPlacebo SION-451
Placebo matched to SION-451
DRUGPlacebo SION-2222
Placebo matched to SION-2222
DRUGPlacebo SION-109
Placebo matched to SION-109
Sponsors
Sionna Therapeutics Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
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.
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 \>470 ms (females) or \>450 ms (males) at Screening or Day -1. 5. Chronic or habitual alcohol (\>10 standard drinks per week) or tobacco (\>10 cigarettes per week) use or use of recreational drugs (\>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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| To evaluate the incidence of treatment emergent adverse events [Safety and Tolerability] of SION-451 and SION-109 when administered in combination to healthy participants | From Day 1 through day 21 | Adverse reactions to the study drug combination SION-451 and SION-109 will be measured. |
| To evaluate the incidence of treatment emergent adverse events [Safety and Tolerability] of SION-451 and SION-2222 when administered in combination to healthy participants | From Day 1 through day 21 | Adverse events to the study drug combination SION-451 and SION-2222 will be measured |
Secondary
| Measure | Time frame |
|---|---|
| Cmax of SION-451 and SION-2222 in plasma when administered in combination to healthy participants | From Day 1 through day 17 |
| Tmax of SION-451 and SION-2222 in plasma when administered in combination to healthy participants | From Day 1 through day 17 |
| AUC of SION-451 and SION-2222 in plasma when administered in combination to healthy participants | From Day 1 through day 17 |
| t1/2 of SION-451 and SION-2222 in plasma when administered in combination to healthy participants | From Day 1 through day 17 |
| Volume of distribution of SION-451 and SION-2222 in plasma when administered in combination to healthy participants | From Day 1 through day 17 |
| Apparent total clearance of SION-451 and SION-2222 in plasma when administered in combination to healthy participants | From Day 1 through day 17 |
| Cmax of SION-451 and SION-109 in plasma when administered in combination to healthy participants | From Day 1 through day 17 |
| Tmax of SION-451 and SION-109 in plasma when administered in combination to healthy participants | From Day 1 through day 17 |
| AUC of SION-451 and SION-109 in plasma when administered in combination to healthy participants | From Day 1 through day 17 |
| t1/2 of SION-451 and SION-109 in plasma when administered in combination to healthy participants | From Day 1 through day 17 |
| Volume of distribution of SION-451 and SION-109 in plasma when administered in combination to healthy participants | From Day 1 through day 17 |
| Apparent total clearance of SION-451 and SION-109 in plasma when administered in combination to healthy participants | From Day 1 through day 17 |
Countries
Australia
Contacts
PRINCIPAL_INVESTIGATORPhilip Ryan, MBBS, BMedSc, PhD, DPM, FFPM
Nucleus Network
Outcome results
None listed