Sickle Cell Disease
Conditions
Brief summary
This first in human study is designed to evaluate the safety, tolerability, pharmacokinetics (PK), and food effect of GBT021601, a hemoglobin S (HbS) polymerization inhibitor, in healthy participants.
Detailed description
This is a randomized, double-blind, placebo controlled, single and multiple ascending dose study in healthy participants.
Interventions
DRUGGBT021601
Administered orally with water as a single dose in the morning.
Sponsors
Pfizer
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
* Healthy males and females ≥ 18 to ≤ 55 years of age * Body mass index ≥ 18.0 to ≤ 30.0 kg/m2 * Body weight ≥ 50 kg at screening and Day -1
Exclusion criteria
\- Positive pregnancy test or currently breastfeeding.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Plasma concentration | 119 days from screening Part A | Time of Cmax |
| Safety, as assessed by changes in eGFR | 119 days from screening Part A, 134 days from screening Part B | Number of participants with changes in eGFR from baseline |
| Safety, as assessed by changes in alanine aminotransferase (ALT) | 119 days from screening Part A, 134 days from screening Part B | Number of participants with changes in alanine aminotransferase (ALT) |
| Safety, as assessed by changes in Blood pressure | 119 days from screening Part A, 134 days from screening Part B | Number of participants with changes in systolic (mmHg) and diastolic (mmHg) blood |
| Safety, as assessed by frequency and severity of adverse events (AEs) | 119 days from screening Part A, 134 days from screening Part B | AEs will be coded to system organ class and preferred term using the Medical Dictionary for Regulatory Activities (MedDRA) and summarized. |
| Safety, as assessed by changes in Heart Rate. | 119 days from screening Part A, 134 days from screening Part B | Number of participants with changes in heart rate (bpm) as compared to baseline. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Determine plasma concentration of GBT021601. | 134 days from screening Part B | With dosing data from each cohort determine the steady-state maximum plasma/whole blood concentration (Cmax). |
| Safety, as assessed by changes in QTcF | 119 days from screening Part A, 134 days from screening Part B | Number of participants with changes in the QTcF interval from baseline |
| Determine whole blood concentration of GBT021601 | 119 days from screening Part A | Hemoximetry will be used to assess oxygen saturation in whole blood by generating oxygen equilibrium curves (OECs) which relate the extent of Hb-O2 saturation to the partial pressure of O2 (pO2) and measure the binding affinity of O2 to Hb. |
Countries
Australia, United States
Outcome results
None listed