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

Sickle Cell Disease Clinical Trial

Official title:

A Phase 4, Open-Label, Single-Center Study to Assess Pharmacokinetic Characteristics and Safety of Endari in Patients With Sickle Cell Disease

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04684381
• Other study ID #: EM-PK-01
• Status: Completed
• Phase: Phase 4
• Start date: January 4, 2021
• Est. completion date: June 30, 2021

Study information

• Verified date: July 2022
• Source: Emmaus Medical, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 13
• Est. completion date: June 30, 2021
• Est. primary completion date: June 30, 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 5 Years and older

Eligibility

Inclusion Criteria:

1. 5 years of age and older at Screening.

2. Has documented diagnosis of SCD with known genotype (HbSS, HbSß0 and HbSC).

3. Written informed consent provided by patient or the patient's legally authorized representative.

4. 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:

1. No known hematologic illness.

2. No known renal impairment.

3. 18 Years of age or older at screening.

4. Written informed consent provided by patient or the patient's legally authorized representative.

5. African American and Hispanic participants preferred.

Exclusion Criteria:

1. Recent significant medical condition that required hospitalization (other than sickle cell crisis) within 2 months prior to starting L-glutamine therapy.

2. History of chronic kidney disease Stage 4 (glomerular filtration rate [GFR]=15-29) or Stage 5 (GFR<15 mL/min/1.73 m2).

3. History of chronic liver disease Child Pugh class C (10-15 points).

4. Received any blood products 3 months prior to starting L-glutamine therapy.

5. Currently pregnant or lactating or planning to conceive during the study period.

6. Currently taking or has taken any form of glutamine supplement within 30 days prior to starting L-glutamine therapy.

7. Has been treated with an investigational medication/treatment within 30 days prior to starting L-glutamine therapy.

8. 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.

9. Factors that would, in the judgment of the investigator, make it difficult for the patient to comply with study requirements.

10. Patient is currently being treated with crizanlizumab or voxelotor.

Exclusion Criteria for Healthy Volunteers:

1. Known allergies to L-glutamine.

2. Informed consent document was not completed and signed.

3. Currently pregnant or lactating or planning to conceive during the study period.

4. Known hematologic illness, renal or hepatic impairment.

5. Received any blood products within 3 months of starting L-glutamine therapy.

Related Conditions & MeSH terms

• Anemia, Sickle Cell
• Pharmacokinetics
• Sickle Cell Disease

Intervention

Drug:
• L-glutamine
Pharmacokinetic study

Locations

Country	Name	City	State
United States	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio

Sponsors (1)

Lead Sponsor	Collaborator
Emmaus Medical, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	PK (AUC)	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)
Primary	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	PK (Cmax)	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)
Primary	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	PK (t1/2)	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)
Primary	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	PK (Tmax)	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)
Secondary	Glutamate levels	Plasma and serum glutamate levels.	Week 1 Day 1, Week 2 Day 1, Week 3 Day 1, Week 4 Day 1.
Secondary	Effect of Food on L-glutamine Area Under Curve (AUC)	Food effect on AUC.	Week 1 Day 1, Week 2 Day 1, Week 4 Day 1.
Secondary	Effect of Food on L-glutamine Maximum Plasma Concentration (Cmax)	Food effect on Cmax.	Week 1 Day 1, Week 2 Day 1, Week 4 Day 1.
Secondary	L-glutamine Dose Effect on Area Under Curve (AUC)	Dose effect on AUC.	Week 1 Day 1, Week 2 Day 1, Week 3 Day 1, Week 4 Day 1.
Secondary	L-glutamine Dose Effect on Maximum Plasma Concentration (Cmax)	Dose effect on Cmax.	Week 1 Day 1, Week 2 Day 1, Week 3 Day 1, Week 4 Day 1.
Secondary	L-glutamine Interpatient Variability of Area Under Curve (AUC)	Interpatient variability of AUC.	Week 1 Day 1, Week 2 Day 1, Week 3 Day 1, Week 4 Day 1.
Secondary	L-glutamine Interpatient Variability of Maximum Plasma Concentration (Cmax)	Interpatient variability of Cmax.	Week 1 Day 1, Week 2 Day 1, Week 3 Day 1, Week 4 Day 1.
Secondary	Ammonia levels	Basal whole blood ammonia levels.	Week 1 Day 1, Week 2 Day 1, Week 3 Day 1, Week 4 Day 1.