Sickle Cell Disease
Conditions
Keywords
Sickle Cell Disease, Hemoglobin subunit beta, fetal hemoglobin, Pharmacokinetics, Pociredir, FTX-6058, Tablet Pharmacokinetics Study, Anemia, Sickle Cell, Hematologic diseases, Small Molecule
Brief summary
This clinical trial is a study to evaluate the pharmacokinetics of the tablet formulation Pociredir in fasted and fed state participants with Sickle Cell Disease (SCD).
Detailed description
The study is designed to assess the pharmacokinetics of the tablet formulation of pociredir under fasted conditions in up to approximately 12 study participants with SCD (Fasted Cohort). An additional cohort of up to approximately 12 study participants with SCD may be enrolled to evaluate the potential effect of food on the PK of the tablet formulation (Fed Cohort). The fasted cohort will be conducted first. The study will include screening period: Day -28 to Day -2; In-patient confinement period: Days -1 to 3; check-in on day -1; single dose of pociredir on day 1; discharge on Day 3; outpatient visit: Day 4; end of study (EOS) visit: Days 8-11 Eligible participants who meet all inclusion and none of the exclusion criteria will be admitted to the clinical site on Day -1, the day before dosing. Participants may be discharged on Day 3 following completion of 48-hour PK sampling or may remain in-clinic through Day 4 if needed. Fasted Cohort: Participants will fast for at least 10 hours prior to dosing and remain fasted for 4 hours post-dose. Water intake will be restricted for 1 hour before and after administration of the investigational medicinal product (IMP). Fed Cohort (if conducted): Participants will fast for at least 10 hours prior to breakfast and will receive a standard high-fat breakfast starting 30 minutes before dosing. Pharmacokinetic samples will be collected up to 72 hours post-dose. Participants are required to remain in-clinic for the first 48 hours post-dose and may return to the site for subsequent Outpatient and EOS visits.
Interventions
DRUGPociredir
Pociredir tablet formulation
Sponsors
Fulcrum Therapeutics
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Documented SCD at the time of screening, as confirmed through review of medical records or high-performance liquid chromatography (HPLC)/electrophoresis. * Participant, who if female and of childbearing potential, agrees to use 2 effective methods of contraception, one which must be highly effective, or practice abstinence starting at the time of the ICF signing to 90 days after the last dose of study drug, and, who if male, agrees to use condoms or practice abstinence from the time of ICF signing to 90 days after the last dose of study drug. * Total Hb ≥ 5.5 grams/deciliter (g/dL) and ≤ 12 g/dL (males) or ≤ 10.6 g/dL (females) at screening * Participant must meet all of the following laboratory values at screening: 1. Absolute neutrophil count ≥ 1.5 × 10\^9/L (cells/liter) 2. Platelets ≥ 80 × 10\^9/L 3. Absolute reticulocyte count \> 100 × 10\^9/L * Participants who meet all other inclusion and
Exclusion criteria
for this study, and per Investigator's recommendation may continue crizanlizumab, and/or L-glutamine, must be on a stable dose for at least 6 months
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Plasma concentration of pociredir under fasted and fed conditions | Day 1 through Day 4 |
| Maximum plasma concentration (Cmax) of pociredir under fasted and fed conditions | Day 1 through Day 4 |
| Area under the plasma concentration-time curve from time 0 to 24 hours (AUC(0-24)) of pociredir under fasted and fed conditions | Day 1 through Day 4 |
| Area under the plasma concentration-time curve from time 0 to the last measurable concentration (AUC(0-tlast)) of pociredir under fasted and fed conditions | Day 1 through Day 4 |
| Area under the plasma concentration-time curve from time 0, extrapolated to infinity (AUC(0-inf)), of pociredir under fasted and fed conditions | Day 1 through Day 4 |
| Time to maximum plasma concentration (Tmax) of pociredir under fasted and fed conditions | Day 1 through Day 4 |
| Terminal disposition rate constant (λz) of pociredir under fasted and fed conditions | Day 1 through Day 4 |
| Terminal half-life (t1/2) of pociredir under fasted and fed conditions | Day 1 through Day 4 |
| Apparent volume of distribution during the terminal phase (Vz/F) of pociredir under fasted and fed conditions | Day 1 through Day 4 |
| Apparent clearance (CL/F) of pociredir under fasted and fed conditions | Day 1 through Day 4 |
Secondary
| Measure | Time frame |
|---|---|
| Number of participants with treatment emergent adverse events (TEAEs) under fasted and fed conditions | Up to Day 11 |
| Number of participants with clinically significant changes in safety assessments under fasted and fed conditions | Up to Day 11 |
| Number of participants with clinically significant findings in clinical laboratory evaluations, vital signs, electrocardiogram (ECGs) and physical examination | Up to Day 11 |
| Plasma concentration of pociredir under fasted and fed conditions compared to healthy participants | Day 1 through Day 4 |
| Cmax of pociredir under fasted and fed conditions compared to healthy participants | Day 1 through Day 4 |
| AUC(0-24) of pociredir under fasted and fed conditions compared to healthy participants | Day 1 through Day 4 |
| AUC(0-tlast) of pociredir under fasted and fed conditions compared to healthy participants | Day 1 through Day 4 |
| AUC(0-inf), under fasted and fed conditions compared to healthy participants | Day 1 through Day 4 |
| Tmax of pociredir under fasted and fed conditions compared to healthy participants | Day 1 through Day 4 |
| λz of pociredir under fasted and fed conditions compared to healthy participants | Day 1 through Day 4 |
| t1/2 of pociredir under fasted and fed conditions compared to healthy participants | Day 1 through Day 4 |
| Vz/F of pociredir under fasted and fed conditions compared to healthy participants | Day 1 through Day 4 |
| CL/F of pociredir under fasted and fed conditions compared to healthy participants | Day 1 through Day 4 |
Countries
United States
Outcome results
None listed