Sickle Cell DiseasePhase 4NCT04684381
Pharmacokinetics and Safety of Endari (L-glutamine) in Sickle Cell Disease Patients
A Phase 4 study testing L-glutamine in people with Sickle Cell Disease and Pharmacokinetics, run by Emmaus Medical, Inc. at 1 site in United States.
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. Read more about this study
- Who is it for?
- Ages 5 years and olderHealthy volunteers can take part
- Conditions the study is for
- Sickle Cell Disease, Pharmacokinetics
- What is being tested?
- L-glutamine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 13 participants
- Where
- 1 siteUnited States
- Study dates
- 4 Jan 2021to 30 Jun 2021
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 5 years and older
- All sexes
- Healthy volunteers accepted
- Child, Adult, Older adult
Who may be able to join
- 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).
- No known hematologic illness.
- No known renal impairment.
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- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229
About this study
Official title: A Phase 4, Open-Label, Single-Center Study to Assess Pharmacokinetic Characteristics and Safety of Endari in Patients With Sickle Cell Disease
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.
Read the 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.
- Conditions
- Sickle Cell Disease, Pharmacokinetics
- Being tested
- L-glutamine
- Keywords
- Sickle cell disease, pharmacokinetics, L-glutamine
- Medical subject headings
- Anemia, Sickle Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
L-glutamineDrug
Also called Endari
Pharmacokinetic study
| Study group | Role | What they receive |
|---|---|---|
| L-glutamine | Experimental | Pharmacokinetic characteristics of L-glutamine Receives: Drug: L-glutamine |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
Measured: 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)
Measured: 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)
Measured: 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)
Measured: 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
Plasma and serum glutamate levels.
Measured: 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)
Food effect on AUC.
Measured: Week 1 Day 1, Week 2 Day 1, Week 4 Day 1.
Effect of Food on L-glutamine Maximum Plasma Concentration (Cmax)
Food effect on Cmax.
Measured: Week 1 Day 1, Week 2 Day 1, Week 4 Day 1.
L-glutamine Dose Effect on Area Under Curve (AUC)
Dose effect on AUC.
Measured: 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)
Dose effect on Cmax.
Measured: Week 1 Day 1, Week 2 Day 1, Week 3 Day 1, Week 4 Day 1.
L-glutamine Interpatient Variability of Area Under Curve (AUC)
Interpatient variability of AUC.
Measured: Week 1 Day 1, Week 2 Day 1, Week 3 Day 1, Week 4 Day 1.
L-glutamine Interpatient Variability of Maximum Plasma Concentration (Cmax)
Interpatient variability of Cmax.
Measured: Week 1 Day 1, Week 2 Day 1, Week 3 Day 1, Week 4 Day 1.
Ammonia levels
Basal whole blood ammonia levels.
Measured: Week 1 Day 1, Week 2 Day 1, Week 3 Day 1, Week 4 Day 1.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Dec 2020
- Study start4 Jan 2021
- Primary completion30 Jun 2021
- Study completion30 Jun 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Sickle Cell DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 13 participants (actual)
Sponsor and investigators
- Lead sponsor
- Emmaus Medical, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Yutaka Niihara, MD, Study chair, Emmaus Medical, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04684381
- Sponsor's protocol ID
- EM-PK-01
- Status last verified
- Jul 2022
- First submitted
- 18 Dec 2020
- Last updated
- 2 Aug 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 38401036
Study at a glance
From the registry record, last updated by the sponsor on 2 Aug 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 4, Open-Label, Single-Center Study to Assess Pharmacokinetic Characteristics and Safety of Endari in Patients With Sickle Cell Disease
- ClinicalTrials.gov ID
- NCT04684381
- Acronym / sponsor ID
- EM-PK-01
- Conditions
- Sickle Cell Disease, Pharmacokinetics
- Keywords
- Sickle cell disease, pharmacokinetics, L-glutamine
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 13 participants (actual)
- Lead sponsor
- Emmaus Medical, Inc.Industry (pharma, biotech, devices)
- Study start
- 4 Jan 2021 (actual)
- Primary completion
- 30 Jun 2021 (actual)
- Study completion
- 30 Jun 2021 (actual)
- First posted
- 24 Dec 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| L-glutamine | Experimental | Drug: L-glutaminePharmacokinetic characteristics of L-glutamine |
Who may qualify
- Ages
- 5 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (9 listed)
- 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).
- No known hematologic illness.
Key exclusion criteria (15 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| L-glutamineAlso: EndariPharmacokinetic study | Drug | L-glutamine |
Primary outcome
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)
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)
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)
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)
8 secondary outcomes
Glutamate levels
Time frame: 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)
Time frame: Week 1 Day 1, Week 2 Day 1, Week 4 Day 1.
Effect of Food on L-glutamine Maximum Plasma Concentration (Cmax)
Time frame: Week 1 Day 1, Week 2 Day 1, Week 4 Day 1.
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.
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.
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.
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.
Ammonia levels
Time frame: Week 1 Day 1, Week 2 Day 1, Week 3 Day 1, Week 4 Day 1.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Aug 2022.
- Derived from this study: PubMed 38401036Sadaf 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Yutaka Niihara, MD study chair
Emmaus Medical, Inc.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing L-glutamine in people with Sickle Cell Disease and Pharmacokinetics, run by Emmaus Medical, Inc. at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 2 Aug 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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)). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04684381, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Aug 2022.