Pharmacokinetics and Safety of Endari (L-glutamine) in Sickle Cell Disease Patients
Study Details
Study Description
Brief Summary
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 4 |
Detailed Description
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: L-glutamine Pharmacokinetic characteristics of L-glutamine |
Drug: L-glutamine
Pharmacokinetic study
Other Names:
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Outcome Measures
Primary Outcome Measures
- Area Under Curve (AUC) of L-glutamine at 0.1 g/kg twice daily, 0.3 g/kg twice daily, and 0.6 g/kg once daily in SCD patients [Week 1 Day 1 (0.1 g/kg dose) and Week 2 Day 1 (0.3 g/kg dose. Week 3 Day 1 and Week4 Day1 (0.6 g/kg once daily dose)]
PK (AUC)
- Maximum Plasma Concentration (Cmax) of L-glutamine at 0.1 g/kg twice daily, 0.3 g/kg twice daily, and 0.6 g/kg once daily in SCD patients [Week 1 Day 1 (0.1 g/kg dose) and Week 2 Day 1 (0.3 g/kg dose. Week 3 Day 1 and Week4 Day1 (0.6 g/kg once daily dose)]
PK (Cmax)
- Half-life (t1/2) of L-glutamine at 0.1 g/kg twice daily, 0.3 g/kg twice daily, and 0.6 g/kg once daily in SCD patients [Week 1 Day 1 (0.1 g/kg dose) and Week 2 Day 1 (0.3 g/kg dose. Week 3 Day 1 and Week4 Day1 (0.6 g/kg once daily dose)]
PK (t1/2)
- Time to Peak Concentration (Tmax) of L-glutamine at 0.1 g/kg twice daily, 0.3 g/kg twice daily, and 0.6 g/kg once daily in SCD patients [Week 1 Day 1 (0.1 g/kg dose) and Week 2 Day 1 (0.3 g/kg dose. Week 3 Day 1 and Week4 Day1 (0.6 g/kg once daily dose)]
PK (Tmax)
Secondary Outcome Measures
- Glutamate levels [Week 1 Day 1, Week 2 Day 1, Week 3 Day 1, Week 4 Day 1.]
Plasma and serum glutamate levels.
- Effect of Food on L-glutamine Area Under Curve (AUC) [Week 1 Day 1, Week 2 Day 1, Week 4 Day 1.]
Food effect on AUC.
- Effect of Food on L-glutamine Maximum Plasma Concentration (Cmax) [Week 1 Day 1, Week 2 Day 1, Week 4 Day 1.]
Food effect on Cmax.
- L-glutamine Dose Effect on Area Under Curve (AUC) [Week 1 Day 1, Week 2 Day 1, Week 3 Day 1, Week 4 Day 1.]
Dose effect on AUC.
- L-glutamine Dose Effect on Maximum Plasma Concentration (Cmax) [Week 1 Day 1, Week 2 Day 1, Week 3 Day 1, Week 4 Day 1.]
Dose effect on Cmax.
- L-glutamine Interpatient Variability of Area Under Curve (AUC) [Week 1 Day 1, Week 2 Day 1, Week 3 Day 1, Week 4 Day 1.]
Interpatient variability of AUC.
- L-glutamine Interpatient Variability of Maximum Plasma Concentration (Cmax) [Week 1 Day 1, Week 2 Day 1, Week 3 Day 1, Week 4 Day 1.]
Interpatient variability of Cmax.
- Ammonia levels [Week 1 Day 1, Week 2 Day 1, Week 3 Day 1, Week 4 Day 1.]
Basal whole blood ammonia levels.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
5 years of age and older at Screening.
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Has documented diagnosis of SCD with known genotype (HbSS, HbSβ0 and HbSC).
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Written informed consent provided by patient or the patient's legally authorized representative.
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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:
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No known hematologic illness.
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No known renal impairment.
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18 Years of age or older at screening.
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Written informed consent provided by patient or the patient's legally authorized representative.
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African American and Hispanic participants preferred.
Exclusion Criteria:
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Recent significant medical condition that required hospitalization (other than sickle cell crisis) within 2 months prior to starting L-glutamine therapy.
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History of chronic kidney disease Stage 4 (glomerular filtration rate [GFR]=15-29) or Stage 5 (GFR<15 mL/min/1.73 m2).
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History of chronic liver disease Child Pugh class C (10-15 points).
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Received any blood products 3 months prior to starting L-glutamine therapy.
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Currently pregnant or lactating or planning to conceive during the study period.
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Currently taking or has taken any form of glutamine supplement within 30 days prior to starting L-glutamine therapy.
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Has been treated with an investigational medication/treatment within 30 days prior to starting L-glutamine therapy.
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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.
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Factors that would, in the judgment of the investigator, make it difficult for the patient to comply with study requirements.
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Patient is currently being treated with crizanlizumab or voxelotor.
Exclusion Criteria for Healthy Volunteers:
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Known allergies to L-glutamine.
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Informed consent document was not completed and signed.
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Currently pregnant or lactating or planning to conceive during the study period.
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Known hematologic illness, renal or hepatic impairment.
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Received any blood products within 3 months of starting L-glutamine therapy.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Cincinnati Children's Hospital Medical Center | Cincinnati | Ohio | United States | 45229 |
Sponsors and Collaborators
- Emmaus Medical, Inc.
Investigators
- Study Chair: Yutaka Niihara, MD, Emmaus Medical, Inc.
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- EM-PK-01