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

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ClinicalTrials.gov Identifier: NCT04684381
Recruitment Status : Recruiting
First Posted : December 24, 2020
Last Update Posted : February 3, 2021
Sponsor:
Information provided by (Responsible Party):
Emmaus Medical, Inc.

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
Sickle Cell Disease Pharmacokinetics Drug: L-glutamine 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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 12 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: A Phase 4, Open-Label, Single-Center Study to Assess Pharmacokinetic Characteristics and Safety of Endari in Patients With Sickle Cell Disease
Actual Study Start Date : January 4, 2021
Estimated Primary Completion Date : February 28, 2022
Estimated Study Completion Date : August 31, 2022

Resource links provided by the National Library of Medicine

Drug Information available for: Glutamine

Arm Intervention/treatment
Experimental: L-glutamine
Pharmacokinetic characteristics of L-glutamine
Drug: L-glutamine
Pharmacokinetic study
Other Name: Endari




Primary Outcome Measures :
  1. 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 [ 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) ]
    PK (AUC)

  2. 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 [ 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) ]
    PK (Cmax)

  3. 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 [ 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) ]
    PK (t1/2)

  4. 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 [ 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) ]
    PK (Tmax)


Secondary Outcome Measures :
  1. Glutamate levels [ Time Frame: Week 1 Day 1, Week 2 Day 1, Week 3 Day 1, Week 4 Day 1. ]
    Plasma and serum glutamate levels.

  2. Effect of Food on L-glutamine Area Under Curve (AUC) [ Time Frame: Week 1 Day 1, Week 2 Day 1, Week 4 Day 1. ]
    Food effect on AUC.

  3. Effect of Food on L-glutamine Maximum Plasma Concentration (Cmax) [ Time Frame: Week 1 Day 1, Week 2 Day 1, Week 4 Day 1. ]
    Food effect on Cmax.

  4. L-glutamine Dose Effect on Area Under Curve (AUC) [ Time Frame: Week 1 Day 1, Week 2 Day 1, Week 3 Day 1, Week 4 Day 1. ]
    Dose effect on AUC.

  5. L-glutamine Dose Effect on Maximum Plasma Concentration (Cmax) [ Time Frame: Week 1 Day 1, Week 2 Day 1, Week 3 Day 1, Week 4 Day 1. ]
    Dose effect on Cmax.

  6. L-glutamine Interpatient Variability of Area Under Curve (AUC) [ Time Frame: Week 1 Day 1, Week 2 Day 1, Week 3 Day 1, Week 4 Day 1. ]
    Interpatient variability of AUC.

  7. L-glutamine Interpatient Variability of Maximum Plasma Concentration (Cmax) [ Time Frame: Week 1 Day 1, Week 2 Day 1, Week 3 Day 1, Week 4 Day 1. ]
    Interpatient variability of Cmax.

  8. Ammonia levels [ Time Frame: Week 1 Day 1, Week 2 Day 1, Week 3 Day 1, Week 4 Day 1. ]
    Basal whole blood ammonia levels.



Information from the National Library of Medicine

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Ages Eligible for Study:   5 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. 5 years of age and older at Screening.
  2. Has documented diagnosis of SCD with known genotype (HbSS, HbSβ0 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04684381


Contacts
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Contact: Joseph Becerra, PharmD 310-214-0065 jbecerra@emmausmedical.com

Locations
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United States, Ohio
Cincinnati Children's Hospital Medical Center Recruiting
Cincinnati, Ohio, United States, 45229
Contact: Latham         
Contact: Pfeiffer         
Sponsors and Collaborators
Emmaus Medical, Inc.
Investigators
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Study Chair: Yutaka Niihara, MD Emmaus Medical, Inc.
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Responsible Party: Emmaus Medical, Inc.
ClinicalTrials.gov Identifier: NCT04684381    
Other Study ID Numbers: EM-PK-01
First Posted: December 24, 2020    Key Record Dates
Last Update Posted: February 3, 2021
Last Verified: February 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Emmaus Medical, Inc.:
Sickle cell disease
pharmacokinetics
L-glutamine
Additional relevant MeSH terms:
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Anemia, Sickle Cell
Anemia, Hemolytic, Congenital
Anemia, Hemolytic
Anemia
Hematologic Diseases
Hemoglobinopathies
Genetic Diseases, Inborn