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

NCT04684381 | Completed Phase 4 FDA Drug

• 1 other identifier: EM-PK-01
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

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.

Conditions

Sickle Cell Disease; Pharmacokinetics

Keywords

Sickle cell disease; pharmacokinetics; L-glutamine

Outcome Measures

Primary Outcomes (4)

• 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)

• 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)

• 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)

• 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 Outcomes (8)

• Glutamate levels

  Week 1 Day 1, Week 2 Day 1, Week 3 Day 1, Week 4 Day 1.

• Effect of Food on L-glutamine Area Under Curve (AUC)

  Week 1 Day 1, Week 2 Day 1, Week 4 Day 1.

• Effect of Food on L-glutamine Maximum Plasma Concentration (Cmax)

  Week 1 Day 1, Week 2 Day 1, Week 4 Day 1.

• 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.

• 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.

Study Arms (1)

L-glutamine

EXPERIMENTAL

Pharmacokinetic characteristics of L-glutamine

Drug: L-glutamine

Interventions

L-glutamine DRUG

Pharmacokinetic study

Also known as: Endari

L-glutamine

Eligibility Criteria

• Age: 5 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).
• No known hematologic illness.
• No known renal impairment.
• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Emmaus Medical, Inc.: lead

Study Sites (1)

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

Related Publications (1)

• Sadaf A, Dong M, Pfeiffer A, Latham T, Kalfa T, Vinks AA, Ware RE, Quinn CT. A Population Pharmacokinetic Analysis of L-Glutamine Exposure in Patients with Sickle Cell Disease: Evaluation of Dose and Food Effects. Clin Pharmacokinet. 2024 Mar;63(3):357-365. doi: 10.1007/s40262-024-01349-4. Epub 2024 Feb 24.

  PMID: 38401036 DERIVED

MeSH Terms

Conditions

Anemia, Sickle Cell

Interventions

Glutamine

Condition Hierarchy (Ancestors)

Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemoglobinopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Amino Acids, Basic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Diamino; Amino Acids, Neutral

Study Officials

• Yutaka Niihara, MD

  Emmaus Medical, Inc.

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 18, 2020
• First Posted: December 24, 2020
• Study Start: January 4, 2021
• Primary Completion: June 30, 2021
• Study Completion: June 30, 2021
• Last Updated: August 2, 2022

Record last verified: 2022-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)