Back to resultsPharmacokinetics and Safety of Endari (L-glutamine) in Sickle Cell Disease Patients
Primary Purpose
Sickle Cell Disease, Pharmacokinetics
Status
Completed
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
L-glutamine
Sponsored by
About this trial
This is an interventional basic science trial for Sickle Cell Disease focused on measuring Sickle cell disease, pharmacokinetics, L-glutamine
Eligibility Criteria
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.
Sites / Locations
- Cincinnati Children's Hospital Medical Center
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
L-glutamine
Arm Description
Pharmacokinetic characteristics of L-glutamine
Outcomes
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
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
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
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
PK (Tmax)
Secondary Outcome Measures
Glutamate levels
Plasma and serum glutamate levels.
Effect of Food on L-glutamine Area Under Curve (AUC)
Food effect on AUC.
Effect of Food on L-glutamine Maximum Plasma Concentration (Cmax)
Food effect on Cmax.
L-glutamine Dose Effect on Area Under Curve (AUC)
Dose effect on AUC.
L-glutamine Dose Effect on Maximum Plasma Concentration (Cmax)
Dose effect on Cmax.
L-glutamine Interpatient Variability of Area Under Curve (AUC)
Interpatient variability of AUC.
L-glutamine Interpatient Variability of Maximum Plasma Concentration (Cmax)
Interpatient variability of Cmax.
Ammonia levels
Basal whole blood ammonia levels.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04684381
Brief Title
Pharmacokinetics and Safety of Endari (L-glutamine) in Sickle Cell Disease Patients
Official Title
A Phase 4, Open-Label, Single-Center Study to Assess Pharmacokinetic Characteristics and Safety of Endari in Patients With Sickle Cell Disease
Study Type
Interventional
2. Study Status
Record Verification Date
July 2022
Overall Recruitment Status
Completed
Study Start Date
January 4, 2021 (Actual)
Primary Completion Date
June 30, 2021 (Actual)
Study Completion Date
June 30, 2021 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Emmaus Medical, Inc.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. 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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Sickle Cell Disease, Pharmacokinetics
Keywords
Sickle cell disease, pharmacokinetics, L-glutamine
7. Study Design
Primary Purpose
Basic Science
Study Phase
Phase 4
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
13 (Actual)
8. Arms, Groups, and Interventions
Arm Title
L-glutamine
Arm Type
Experimental
Arm Description
Pharmacokinetic characteristics of L-glutamine
Intervention Type
Drug
Intervention Name(s)
L-glutamine
Other Intervention Name(s)
Endari
Intervention Description
Pharmacokinetic study
Primary Outcome Measure Information:
Title
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
Description
PK (AUC)
Time Frame
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)
Title
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
Description
PK (Cmax)
Time Frame
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)
Title
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
Description
PK (t1/2)
Time Frame
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)
Title
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
Description
PK (Tmax)
Time Frame
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 Outcome Measure Information:
Title
Glutamate levels
Description
Plasma and serum glutamate levels.
Time Frame
Week 1 Day 1, Week 2 Day 1, Week 3 Day 1, Week 4 Day 1.
Title
Effect of Food on L-glutamine Area Under Curve (AUC)
Description
Food effect on AUC.
Time Frame
Week 1 Day 1, Week 2 Day 1, Week 4 Day 1.
Title
Effect of Food on L-glutamine Maximum Plasma Concentration (Cmax)
Description
Food effect on Cmax.
Time Frame
Week 1 Day 1, Week 2 Day 1, Week 4 Day 1.
Title
L-glutamine Dose Effect on Area Under Curve (AUC)
Description
Dose effect on AUC.
Time Frame
Week 1 Day 1, Week 2 Day 1, Week 3 Day 1, Week 4 Day 1.
Title
L-glutamine Dose Effect on Maximum Plasma Concentration (Cmax)
Description
Dose effect on Cmax.
Time Frame
Week 1 Day 1, Week 2 Day 1, Week 3 Day 1, Week 4 Day 1.
Title
L-glutamine Interpatient Variability of Area Under Curve (AUC)
Description
Interpatient variability of AUC.
Time Frame
Week 1 Day 1, Week 2 Day 1, Week 3 Day 1, Week 4 Day 1.
Title
L-glutamine Interpatient Variability of Maximum Plasma Concentration (Cmax)
Description
Interpatient variability of Cmax.
Time Frame
Week 1 Day 1, Week 2 Day 1, Week 3 Day 1, Week 4 Day 1.
Title
Ammonia levels
Description
Basal whole blood ammonia levels.
Time Frame
Week 1 Day 1, Week 2 Day 1, Week 3 Day 1, Week 4 Day 1.
10. Eligibility
Sex
All
Minimum Age & Unit of Time
5 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Yutaka Niihara, MD
Organizational Affiliation
Emmaus Medical, Inc.
Official's Role
Study Chair
Facility Information:
Facility Name
Cincinnati Children's Hospital Medical Center
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45229
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Pharmacokinetics and Safety of Endari (L-glutamine) in Sickle Cell Disease Patients
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