Pharmacokinetics and Safety of Endari (L-glutamine) in Sickle Cell Disease Patients

Sickle cell disease (SCD) is associated with a mutation in the β-hemoglobin gene that results in abnormal polymerization of hemoglobin. Polymerization of hemoglobin causes the red blood cell to sickle, leading to a cascade of events which cause acute complications for SCD patients.

L-glutamine has been approved in the US to reduce the acute complications of sickle cell disease (SCD) in adult and pediatric patients 5 years of age and older.

The purpose of this single-center, open-label, phase 4 study is to evaluate the pharmacokinetic characteristics and safety of L-glutamine in patients with SCD.

8 SCD patients and 4 healthy volunteers will receive weight-based dosing of L-glutamine for 3 weeks. Doses will be changed weekly: 0.1 g/kg administered twice daily during week 1, 0.3 g/kg administered twice daily during week 2, and 0.6 g/kg administered once daily during week 3.

The primary objective is to evaluate the pharmacokinetic characteristics of L-glutamine in SCD patients compared with healthy volunteers.

Inclusion criteria

• 5 years of age and older at Screening.
• Has documented diagnosis of SCD with known genotype (HbSS, HbSβ0 and HbSC).
• Written informed consent provided by patient or the patient's legally authorized representative.
• Non-pregnant females of childbearing age must agree to avoid pregnancy during the study and to practice a recognized form of birth control during the course of the study (e.g., barrier, birth control pills, or abstinence).

Inclusion criteria

for Healthy Volunteers:

• No known hematologic illness.
• No known renal impairment.
• 18 Years of age or older at screening.
• Written informed consent provided by patient or the patient's legally authorized representative.
• African American and Hispanic participants preferred.

Exclusion criteria

• Recent significant medical condition that required hospitalization (other than sickle cell crisis) within 2 months prior to starting L-glutamine therapy.
• History of chronic kidney disease Stage 4 (glomerular filtration rate [GFR]=15-29) or Stage 5 (GFR<15 mL/min/1.73 m2).
• History of chronic liver disease Child Pugh class C (10-15 points).
• Received any blood products 3 months prior to starting L-glutamine therapy.
• Currently pregnant or lactating or planning to conceive during the study period.
• Currently taking or has taken any form of glutamine supplement within 30 days prior to starting L-glutamine therapy.
• Has been treated with an investigational medication/treatment within 30 days prior to starting L-glutamine therapy.
• Is currently enrolled in an investigational drug or device study and/or has participated in such a study within 30 days prior to starting L-glutamine therapy.
• Factors that would, in the judgment of the investigator, make it difficult for the patient to comply with study requirements.
• Patient is currently being treated with crizanlizumab or voxelotor.

Exclusion criteria

for Healthy Volunteers:

• Known allergies to L-glutamine.
• Informed consent document was not completed and signed.
• Currently pregnant or lactating or planning to conceive during the study period.
• Known hematologic illness, renal or hepatic impairment.
• Received any blood products within 3 months of starting L-glutamine therapy.