Trial Outcomes & Findings for L-Glutamine Therapy for Sickle Cell Anemia and Sickle ß0 Thalassemia (NCT NCT00125788)

NCT ID: NCT00125788

Last Updated: 2021-01-29

Results Overview

The mean number of painful sickle crisis through week 48

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 70 participants
• Primary outcome timeframe: From Week 0 through Week 48 (cumulative)
• Results posted on: 2021-01-29

Participant Flow

Participant milestones

Measure	Investigational Product L-glutamine L-glutamine: Approximately 0.3 g/kg total daily dose of L-glutamine will be orally administered (over two doses), with a maximum total daily dose of 30 grams.	Placebo maltodextrin Placebo: Approximately 0.3 g/kg total daily dose of maltodextrin placebo will be orally administered (over two doses), with a maximum total daily dose of 30 grams.
Overall Study STARTED	37	33
Overall Study COMPLETED	33	29
Overall Study NOT COMPLETED	4	4

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

L-Glutamine Therapy for Sickle Cell Anemia and Sickle ß0 Thalassemia

Baseline characteristics by cohort

Measure	Investigational Product n=33 Participants L-glutamine L-glutamine: Approximately 0.3 g/kg total daily dose of L-glutamine will be orally administered (over two doses), with a maximum total daily dose of 30 grams.	Placebo n=29 Participants maltodextrin Placebo: Approximately 0.3 g/kg total daily dose of maltodextrin placebo will be orally administered (over two doses), with a maximum total daily dose of 30 grams.	Total n=62 Participants Total of all reporting groups
Age, Categorical <=18 years	3 Participants n=5 Participants	3 Participants n=7 Participants	6 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	30 Participants n=5 Participants	26 Participants n=7 Participants	56 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Continuous	30.5 years STANDARD_DEVIATION 10.09 • n=5 Participants	26.5 years STANDARD_DEVIATION 9.42 • n=7 Participants	28.6 years STANDARD_DEVIATION 13.8 • n=5 Participants
Sex: Female, Male Female	22 Participants n=5 Participants	10 Participants n=7 Participants	32 Participants n=5 Participants
Sex: Female, Male Male	11 Participants n=5 Participants	19 Participants n=7 Participants	30 Participants n=5 Participants
Region of Enrollment United States	33 participants n=5 Participants	29 participants n=7 Participants	62 participants n=5 Participants

PRIMARY outcome

Timeframe: From Week 0 through Week 48 (cumulative)

Population: The full analysis dataset included all patients who received at least one dose of study medication and had been diagnosed with sickle cell anemia or sickle β°-thalassemia documented by hemoglobin electrophoresis and had at least 2 episodes of painful crises within 12 months prior to the screening visit (N = 62)

The mean number of painful sickle crisis through week 48

Outcome measures

Measure	Investigational Product n=33 Participants L-glutamine L-glutamine: Approximately 0.3 g/kg total daily dose of L-glutamine will be orally administered (over two doses), with a maximum total daily dose of 30 grams.	Placebo n=29 Participants maltodextrin Placebo: Approximately 0.3 g/kg total daily dose of maltodextrin placebo will be orally administered (over two doses), with a maximum total daily dose of 30 grams.
Number of Occurrences of Painful Sickle Cell Crises	4.5 Crisis Standard Deviation 5.37	10.8 Crisis Standard Deviation 18.74

SECONDARY outcome

Timeframe: From Week 0 through Week 48 (cumulative)

Population: The full analysis dataset included all patients who received at least one dose of study medication and had been diagnosed with sickle cell anemia or sickle β°-thalassemia documented by hemoglobin electrophoresis and had at least 2 episodes of painful crises within 12 months prior to the screening visit (N = 62).

The mean number of hospitalizations through week 48

Outcome measures

Measure	Investigational Product n=33 Participants L-glutamine L-glutamine: Approximately 0.3 g/kg total daily dose of L-glutamine will be orally administered (over two doses), with a maximum total daily dose of 30 grams.	Placebo n=29 Participants maltodextrin Placebo: Approximately 0.3 g/kg total daily dose of maltodextrin placebo will be orally administered (over two doses), with a maximum total daily dose of 30 grams.
Frequency of Hospitalizations for Sickle Cell Pain	1.5 Hosptalizations Standard Deviation 2.46	2.3 Hosptalizations Standard Deviation 2.42

SECONDARY outcome

Timeframe: From Week 0 through Week 48 (cumulative)

Population: The full analysis dataset included all patients who received at least one dose of study medication and had been diagnosed with sickle cell anemia or sickle β°-thalassemia documented by hemoglobin electrophoresis and had at least 2 episodes of painful crises within 12 months prior to the screening visit (N = 62).

The mean number of emergency room visits through week 48

Outcome measures

Measure	Investigational Product n=33 Participants L-glutamine L-glutamine: Approximately 0.3 g/kg total daily dose of L-glutamine will be orally administered (over two doses), with a maximum total daily dose of 30 grams.	Placebo n=29 Participants maltodextrin Placebo: Approximately 0.3 g/kg total daily dose of maltodextrin placebo will be orally administered (over two doses), with a maximum total daily dose of 30 grams.
Frequency of Emergency Room Visits for Sickle Cell Pain	3.7 Emergency room visits Standard Deviation 5.63	9.4 Emergency room visits Standard Deviation 19.91

SECONDARY outcome

Timeframe: Baseline, Weeks 4, 24 and 40

Population: The safety population included all patients who received at least one dose of study medication (N = 70).

Patient's hemoglobin will be collected at each visit.Change from Baseline will be reported at Weeks 4, 24 and 40.

Outcome measures

Measure	Investigational Product n=37 Participants L-glutamine L-glutamine: Approximately 0.3 g/kg total daily dose of L-glutamine will be orally administered (over two doses), with a maximum total daily dose of 30 grams.	Placebo n=33 Participants maltodextrin Placebo: Approximately 0.3 g/kg total daily dose of maltodextrin placebo will be orally administered (over two doses), with a maximum total daily dose of 30 grams.
The Effect of Oral L-glutamine on Hematological Parameters - Hemoglobin Baseline	8.96 g/dL Standard Deviation 1.477	9.05 g/dL Standard Deviation 1.219
The Effect of Oral L-glutamine on Hematological Parameters - Hemoglobin Change in Hemoglobin at Week 4	0.15 g/dL Standard Deviation 0.831	-0.13 g/dL Standard Deviation 0.861
The Effect of Oral L-glutamine on Hematological Parameters - Hemoglobin Change in Hemoglobin at Week 24	0.26 g/dL Standard Deviation 0.641	0.16 g/dL Standard Deviation 0.607
The Effect of Oral L-glutamine on Hematological Parameters - Hemoglobin Change in Hemoglobin at Week 40	0.11 g/dL Standard Deviation 0.749	-0.07 g/dL Standard Deviation 0.650

SECONDARY outcome

Timeframe: Baseline, Weeks 4, 24, and 40

Population: The safety population included all patients who received at least one dose of study medication (N = 70).

Patient's hematocrit will be collected at each visit. Change from Baseline will be reported at Weeks 4, 24 and 40

Outcome measures

Measure	Investigational Product n=37 Participants L-glutamine L-glutamine: Approximately 0.3 g/kg total daily dose of L-glutamine will be orally administered (over two doses), with a maximum total daily dose of 30 grams.	Placebo n=33 Participants maltodextrin Placebo: Approximately 0.3 g/kg total daily dose of maltodextrin placebo will be orally administered (over two doses), with a maximum total daily dose of 30 grams.
The Effect of Oral L-glutamine on Hematological Parameters - Hematocrit Change in Hematocrit at Week 4	0.51 % RBC Standard Deviation 2.784	-0.09 % RBC Standard Deviation 2.279
The Effect of Oral L-glutamine on Hematological Parameters - Hematocrit Baseline	25.90 % RBC Standard Deviation 4.493	26.22 % RBC Standard Deviation 4.125
The Effect of Oral L-glutamine on Hematological Parameters - Hematocrit Change in Hematocrit at Week 24	1.08 % RBC Standard Deviation 2.352	0.58 % RBC Standard Deviation 2.050
The Effect of Oral L-glutamine on Hematological Parameters - Hematocrit Change in Hematocrit at Week 40	0.49 % RBC Standard Deviation 2.786	0.26 % RBC Standard Deviation 1.869

SECONDARY outcome

Timeframe: Baseline, Weeks 0, 4, 24, 40

Population: The safety population included all patients who received at least one dose of study medication (N = 70).

Patient's reticulocyte count will be collected at each visit. Change from Baseline will be reported at Weeks 4, 24 and 40

Outcome measures

Measure	Investigational Product n=37 Participants L-glutamine L-glutamine: Approximately 0.3 g/kg total daily dose of L-glutamine will be orally administered (over two doses), with a maximum total daily dose of 30 grams.	Placebo n=33 Participants maltodextrin Placebo: Approximately 0.3 g/kg total daily dose of maltodextrin placebo will be orally administered (over two doses), with a maximum total daily dose of 30 grams.
The Effect of Oral L-glutamine on Hematological Parameters - Reticulocyte Count Baseline	0.266 10^12 Reticulocytes/L Standard Deviation 0.1125	0.295 10^12 Reticulocytes/L Standard Deviation 0.0979
The Effect of Oral L-glutamine on Hematological Parameters - Reticulocyte Count Change in Reticulocyte count at Week 4	-0.040 10^12 Reticulocytes/L Standard Deviation 0.0993	-0.034 10^12 Reticulocytes/L Standard Deviation 0.0689
The Effect of Oral L-glutamine on Hematological Parameters - Reticulocyte Count Change in Reticulocyte count at Week 24	-0.022 10^12 Reticulocytes/L Standard Deviation 0.0917	-0.032 10^12 Reticulocytes/L Standard Deviation 0.1032
The Effect of Oral L-glutamine on Hematological Parameters - Reticulocyte Count Change in Reticulocyte count at Week 40	-0.016 10^12 Reticulocytes/L Standard Deviation 0.1357	-0.020 10^12 Reticulocytes/L Standard Deviation 0.0908

SECONDARY outcome

Timeframe: Week 24, Week 48

Population: Patients with any narcotic use who completed the visit

Analysis of narcotic usage was performed for the subset of patients with any narcotic use who completed the study. Changes in narcotic usage were determined by an independent consultant prior to database lock using morphine equivalents to determine relative use.

Outcome measures

Measure	Investigational Product n=17 Participants L-glutamine L-glutamine: Approximately 0.3 g/kg total daily dose of L-glutamine will be orally administered (over two doses), with a maximum total daily dose of 30 grams.	Placebo n=16 Participants maltodextrin Placebo: Approximately 0.3 g/kg total daily dose of maltodextrin placebo will be orally administered (over two doses), with a maximum total daily dose of 30 grams.
Number of Participants With Narcotic Usage Change in Narcotic Usage at Week 24 · Change to weaker narcotics	6 Participants	2 Participants
Number of Participants With Narcotic Usage Change in Narcotic Usage at Week 24 · No change	10 Participants	9 Participants
Number of Participants With Narcotic Usage Change in Narcotic Usage at Week 24 · Change to stronger narcotics	1 Participants	5 Participants
Number of Participants With Narcotic Usage Change in Narcotic Usage at Week 48 · Change to weaker narcotics	6 Participants	2 Participants
Number of Participants With Narcotic Usage Change in Narcotic Usage at Week 48 · No change	10 Participants	9 Participants
Number of Participants With Narcotic Usage Change in Narcotic Usage at Week 48 · Change to stronger narcotics	1 Participants	5 Participants

SECONDARY outcome

Timeframe: Collected at Week 0, 8, 16, 24, 32, 40, 48

Population: The full analysis dataset included all patients who received at least one dose of study medication and had been diagnosed with sickle cell anemia or sickle β°-thalassemia documented by hemoglobin electrophoresis and had at least 2 episodes of painful crises within 12 months prior to the screening visit (N = 62).

The patient's energy level was evaluated at each visit using an 11 point scale from 0=extremely tired to 10=extremely energetic

Outcome measures

Measure	Investigational Product n=33 Participants L-glutamine L-glutamine: Approximately 0.3 g/kg total daily dose of L-glutamine will be orally administered (over two doses), with a maximum total daily dose of 30 grams.	Placebo n=29 Participants maltodextrin Placebo: Approximately 0.3 g/kg total daily dose of maltodextrin placebo will be orally administered (over two doses), with a maximum total daily dose of 30 grams.
Energy Level (11-point Scale) Week 0	6.1 score on a scale Standard Deviation 1.92	6.8 score on a scale Standard Deviation 1.99
Energy Level (11-point Scale) Week 8	6.9 score on a scale Standard Deviation 1.84	7.1 score on a scale Standard Deviation 1.96
Energy Level (11-point Scale) Week 16	6.9 score on a scale Standard Deviation 2.02	7.1 score on a scale Standard Deviation 2.70
Energy Level (11-point Scale) Week 24	7.3 score on a scale Standard Deviation 1.65	7.8 score on a scale Standard Deviation 2.02
Energy Level (11-point Scale) Week 32	7.3 score on a scale Standard Deviation 1.67	7.4 score on a scale Standard Deviation 1.95
Energy Level (11-point Scale) Week40	6.6 score on a scale Standard Deviation 1.54	6.9 score on a scale Standard Deviation 2.29
Energy Level (11-point Scale) Week 48	6.8 score on a scale Standard Deviation 1.92	7.3 score on a scale Standard Deviation 1.83

SECONDARY outcome

Timeframe: Collected at Week 0, 8, 16, 24, 32, 40, 48

Population: The full analysis dataset included all patients who received at least one dose of study medication and had been diagnosed with sickle cell anemia or sickle β°-thalassemia documented by hemoglobin electrophoresis and had at least 2 episodes of painful crises within 12 months prior to the screening visit (N = 62).

Patient's appetite level was evaluated at each visit using a 3 point scale: above average, average and below average. The parentages of patient at each visit whose appetite level was below, normal or above average were compared using CMH test (row mean scores) controlling for study center.

Outcome measures

Measure	Investigational Product n=33 Participants L-glutamine L-glutamine: Approximately 0.3 g/kg total daily dose of L-glutamine will be orally administered (over two doses), with a maximum total daily dose of 30 grams.	Placebo n=29 Participants maltodextrin Placebo: Approximately 0.3 g/kg total daily dose of maltodextrin placebo will be orally administered (over two doses), with a maximum total daily dose of 30 grams.
Patient Appetite (3-point Scale) Patient appetite since the last visit - Visit 0 · Above average	4 Participants	6 Participants
Patient Appetite (3-point Scale) Patient appetite since the last visit - Visit 0 · Average	24 Participants	22 Participants
Patient Appetite (3-point Scale) Patient appetite since the last visit - Visit 0 · Below average	5 Participants	1 Participants
Patient Appetite (3-point Scale) Patient appetite since the last visit - Visit 0 · Not known	0 Participants	0 Participants
Patient Appetite (3-point Scale) Patient appetite since the last visit - Visit 8 · Above average	4 Participants	6 Participants
Patient Appetite (3-point Scale) Patient appetite since the last visit - Visit 8 · Average	19 Participants	14 Participants
Patient Appetite (3-point Scale) Patient appetite since the last visit - Visit 8 · Below average	2 Participants	2 Participants
Patient Appetite (3-point Scale) Patient appetite since the last visit - Visit 8 · Not known	1 Participants	0 Participants
Patient Appetite (3-point Scale) Patient appetite since the last visit - Visit 16 · Above average	3 Participants	9 Participants
Patient Appetite (3-point Scale) Patient appetite since the last visit - Visit 16 · Average	18 Participants	11 Participants
Patient Appetite (3-point Scale) Patient appetite since the last visit - Visit 16 · Below average	7 Participants	2 Participants
Patient Appetite (3-point Scale) Patient appetite since the last visit - Visit 16 · Not known	0 Participants	0 Participants
Patient Appetite (3-point Scale) Patient appetite since the last visit - Visit 24 · Above average	4 Participants	7 Participants
Patient Appetite (3-point Scale) Patient appetite since the last visit - Visit 24 · Average	17 Participants	11 Participants
Patient Appetite (3-point Scale) Patient appetite since the last visit - Visit 24 · Below average	1 Participants	2 Participants
Patient Appetite (3-point Scale) Patient appetite since the last visit - Visit 24 · Not known	0 Participants	0 Participants
Patient Appetite (3-point Scale) Patient appetite since the last visit - Visit 32 · Above average	3 Participants	3 Participants
Patient Appetite (3-point Scale) Patient appetite since the last visit - Visit 32 · Average	15 Participants	12 Participants
Patient Appetite (3-point Scale) Patient appetite since the last visit - Visit 32 · Below average	1 Participants	0 Participants
Patient Appetite (3-point Scale) Patient appetite since the last visit - Visit 32 · Not known	0 Participants	0 Participants
Patient Appetite (3-point Scale) Patient appetite since the last visit - Visit 40 · Above average	2 Participants	4 Participants
Patient Appetite (3-point Scale) Patient appetite since the last visit - Visit 40 · Average	13 Participants	7 Participants
Patient Appetite (3-point Scale) Patient appetite since the last visit - Visit 40 · Below average	3 Participants	2 Participants
Patient Appetite (3-point Scale) Patient appetite since the last visit - Visit 40 · Not known	0 Participants	0 Participants
Patient Appetite (3-point Scale) Patient appetite since the last visit - Visit 48 · Above average	2 Participants	2 Participants
Patient Appetite (3-point Scale) Patient appetite since the last visit - Visit 48 · Average	13 Participants	9 Participants
Patient Appetite (3-point Scale) Patient appetite since the last visit - Visit 48 · Below average	2 Participants	1 Participants
Patient Appetite (3-point Scale) Patient appetite since the last visit - Visit 48 · Not known	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Baseline, Weeks 4, 24, and 48

Population: The safety population included all patients who received at least one dose of study medication (N = 70).

Patient's blood pressure will be collected at each visit. Change from Baseline will be reported at Weeks 4, 24, and 48

Outcome measures

Measure	Investigational Product n=37 Participants L-glutamine L-glutamine: Approximately 0.3 g/kg total daily dose of L-glutamine will be orally administered (over two doses), with a maximum total daily dose of 30 grams.	Placebo n=33 Participants maltodextrin Placebo: Approximately 0.3 g/kg total daily dose of maltodextrin placebo will be orally administered (over two doses), with a maximum total daily dose of 30 grams.
The Effect of Oral L-glutamine on Vital Signs - Blood Pressure Baseline SBP (mm/Hg)	115.18 mm/Hg Standard Deviation 14.30	119.6 mm/Hg Standard Deviation 13.64
The Effect of Oral L-glutamine on Vital Signs - Blood Pressure Change in SBP (mm/Hg) at Week 4	0.7 mm/Hg Standard Deviation 10.98	-0.9 mm/Hg Standard Deviation 10.81
The Effect of Oral L-glutamine on Vital Signs - Blood Pressure Change in SBP (mm/Hg) at Week 24	2.2 mm/Hg Standard Deviation 10.48	-1.9 mm/Hg Standard Deviation 13.06
The Effect of Oral L-glutamine on Vital Signs - Blood Pressure Change in SBP (mm/Hg) at Week 48	-1.2 mm/Hg Standard Deviation 12.07	-1.5 mm/Hg Standard Deviation 12.97
The Effect of Oral L-glutamine on Vital Signs - Blood Pressure Baseline DBP (mm/hg)	63.7 mm/Hg Standard Deviation 9.05	64.9 mm/Hg Standard Deviation 8.09
The Effect of Oral L-glutamine on Vital Signs - Blood Pressure Change in DBP (mm/Hg) at Week 4	1.2 mm/Hg Standard Deviation 8.09	2.2 mm/Hg Standard Deviation 8.73
The Effect of Oral L-glutamine on Vital Signs - Blood Pressure Change in DBP (mm/Hg) at Week 24	1.2 mm/Hg Standard Deviation 9.55	-0.4 mm/Hg Standard Deviation 6.88
The Effect of Oral L-glutamine on Vital Signs - Blood Pressure Change in DBP (mm/Hg) at Week 48	-1.3 mm/Hg Standard Deviation 7.98	0.5 mm/Hg Standard Deviation 7.91

SECONDARY outcome

Timeframe: Baseline, Weeks 4, 24, and 48

Population: The safety population included all patients who received at least one dose of study medication (N = 70).

Patient's temperature will be collected at each visit. Change from Baseline will be reported at Weeks 4, 24, and 48

Outcome measures

Measure	Investigational Product n=37 Participants L-glutamine L-glutamine: Approximately 0.3 g/kg total daily dose of L-glutamine will be orally administered (over two doses), with a maximum total daily dose of 30 grams.	Placebo n=33 Participants maltodextrin Placebo: Approximately 0.3 g/kg total daily dose of maltodextrin placebo will be orally administered (over two doses), with a maximum total daily dose of 30 grams.
The Effect of Oral L-glutamine on Vital Signs - Temperature Baseline	36.40 deg C Standard Deviation 0.686	36.29 deg C Standard Deviation 0.613
The Effect of Oral L-glutamine on Vital Signs - Temperature Change in Temperature at Week 4	-0.05 deg C Standard Deviation 0.377	-0.06 deg C Standard Deviation 0.269
The Effect of Oral L-glutamine on Vital Signs - Temperature Change Temperature at Week 24	-0.01 deg C Standard Deviation 0.261	-0.07 deg C Standard Deviation 0.268
The Effect of Oral L-glutamine on Vital Signs - Temperature Change in Temperature at Week 48	0.08 deg C Standard Deviation 0.362	-0.09 deg C Standard Deviation 0.256

SECONDARY outcome

Timeframe: Baseline, Weeks 4, 24, and 48

Population: The safety population included all patients who received at least one dose of study medication (N = 70).

Respiration will be collected at each visit. Change from Baseline will be reported at Weeks 4, 24, and 48

Outcome measures

Measure	Investigational Product n=37 Participants L-glutamine L-glutamine: Approximately 0.3 g/kg total daily dose of L-glutamine will be orally administered (over two doses), with a maximum total daily dose of 30 grams.	Placebo n=33 Participants maltodextrin Placebo: Approximately 0.3 g/kg total daily dose of maltodextrin placebo will be orally administered (over two doses), with a maximum total daily dose of 30 grams.
The Effect of Oral L-glutamine on Vital Signs - Respiration Baseline	17.9 resp/min Standard Deviation 2.11	17.7 resp/min Standard Deviation 1.94
The Effect of Oral L-glutamine on Vital Signs - Respiration Change in Respiration at Week 4	0.3 resp/min Standard Deviation 1.71	0.6 resp/min Standard Deviation 1.58
The Effect of Oral L-glutamine on Vital Signs - Respiration Change in Respiration at Week 24	0.4 resp/min Standard Deviation 1.73	-0.4 resp/min Standard Deviation 1.93
The Effect of Oral L-glutamine on Vital Signs - Respiration Change in Respiration at Week 48	0.4 resp/min Standard Deviation 2.12	0.6 resp/min Standard Deviation 2.47

SECONDARY outcome

Timeframe: Baseline, Weeks 4, 24, and 48

Population: The safety population included all patients who received at least one dose of study medication (N = 70).

Patient's pulse rate will be collected at each visit, Change from Baseline will be reported at Weeks 4, 24, and 48

Outcome measures

Measure	Investigational Product n=37 Participants L-glutamine L-glutamine: Approximately 0.3 g/kg total daily dose of L-glutamine will be orally administered (over two doses), with a maximum total daily dose of 30 grams.	Placebo n=33 Participants maltodextrin Placebo: Approximately 0.3 g/kg total daily dose of maltodextrin placebo will be orally administered (over two doses), with a maximum total daily dose of 30 grams.
The Effect of Oral L-glutamine on Vital Signs - Pulse Rate Baseline	81.6 bpm Standard Deviation 11.37	80.5 bpm Standard Deviation 11.95
The Effect of Oral L-glutamine on Vital Signs - Pulse Rate Change in Pulse Rate at Week 4	2.5 bpm Standard Deviation 12.88	0.7 bpm Standard Deviation 12.11
The Effect of Oral L-glutamine on Vital Signs - Pulse Rate Change in Pulse Rate at Week 24	1.7 bpm Standard Deviation 13.69	-2.7 bpm Standard Deviation 12.81
The Effect of Oral L-glutamine on Vital Signs - Pulse Rate Change in Pulse Rate at Week 48	1.3 bpm Standard Deviation 14.53	3.9 bpm Standard Deviation 10.07

SECONDARY outcome

Timeframe: Weeks 0, 8,16, 24, 32, 40 and 48

Population: The full analysis dataset included all patients who received at least one dose of study medication and had been diagnosed with sickle cell anemia or sickle β°-thalassemia documented by hemoglobin electrophoresis and had at least 2 episodes of painful crises within 12 months prior to the screening visit (N = 62)

The patient's alcohol usage will be assessed at each visit. Alcohol usage will be reported at Weeks 0, 8,16, 24, 32, 40 and 48

Outcome measures

Measure	Investigational Product n=33 Participants L-glutamine L-glutamine: Approximately 0.3 g/kg total daily dose of L-glutamine will be orally administered (over two doses), with a maximum total daily dose of 30 grams.	Placebo n=29 Participants maltodextrin Placebo: Approximately 0.3 g/kg total daily dose of maltodextrin placebo will be orally administered (over two doses), with a maximum total daily dose of 30 grams.
Effect of L-glutamine on Alcohol Use Week 0 · NO - Alcohol Use	30 Participants	27 Participants
Effect of L-glutamine on Alcohol Use Week 0 · YES - Alcohol Use	3 Participants	2 Participants
Effect of L-glutamine on Alcohol Use Week 8 · NO - Alcohol Use	25 Participants	20 Participants
Effect of L-glutamine on Alcohol Use Week 8 · YES - Alcohol Use	1 Participants	2 Participants
Effect of L-glutamine on Alcohol Use Week 16 · NO - Alcohol Use	27 Participants	20 Participants
Effect of L-glutamine on Alcohol Use Week 16 · YES - Alcohol Use	1 Participants	2 Participants
Effect of L-glutamine on Alcohol Use Week 24 · NO - Alcohol Use	22 Participants	19 Participants
Effect of L-glutamine on Alcohol Use Week 24 · YES - Alcohol Use	0 Participants	1 Participants
Effect of L-glutamine on Alcohol Use Week 32 · NO - Alcohol Use	19 Participants	13 Participants
Effect of L-glutamine on Alcohol Use Week 32 · YES - Alcohol Use	0 Participants	2 Participants
Effect of L-glutamine on Alcohol Use Week 40 · NO - Alcohol Use	18 Participants	11 Participants
Effect of L-glutamine on Alcohol Use Week 40 · YES - Alcohol Use	0 Participants	2 Participants
Effect of L-glutamine on Alcohol Use Week 48 · NO - Alcohol Use	17 Participants	11 Participants
Effect of L-glutamine on Alcohol Use Week 48 · YES - Alcohol Use	0 Participants	1 Participants

SECONDARY outcome

Timeframe: Weeks 0, 8,16, 24, 32, 40 and 48

Population: The full analysis dataset included all patients who received at least one dose of study medication and had been diagnosed with sickle cell anemia or sickle β°-thalassemia documented by hemoglobin electrophoresis and had at least 2 episodes of painful crises within 12 months prior to the screening visit (N = 62)

Patient's alcohol usage will be assessed at each visit. Alcohol usage will be reported at Weeks 0, 8,16, 24, 32, 40 and 48

Outcome measures

Measure	Investigational Product n=33 Participants L-glutamine L-glutamine: Approximately 0.3 g/kg total daily dose of L-glutamine will be orally administered (over two doses), with a maximum total daily dose of 30 grams.	Placebo n=29 Participants maltodextrin Placebo: Approximately 0.3 g/kg total daily dose of maltodextrin placebo will be orally administered (over two doses), with a maximum total daily dose of 30 grams.
Effect of L-glutamine on Tobacco Use Week 0 · NO - Tobacco use	28 Participants	27 Participants
Effect of L-glutamine on Tobacco Use Week 0 · YES - Tobacco use	5 Participants	2 Participants
Effect of L-glutamine on Tobacco Use Week 8 · NO - Tobacco use	23 Participants	21 Participants
Effect of L-glutamine on Tobacco Use Week 8 · YES - Tobacco use	3 Participants	1 Participants
Effect of L-glutamine on Tobacco Use Week 16 · NO - Tobacco use	24 Participants	22 Participants
Effect of L-glutamine on Tobacco Use Week 16 · YES - Tobacco use	4 Participants	0 Participants
Effect of L-glutamine on Tobacco Use Week 24 · NO - Tobacco use	20 Participants	19 Participants
Effect of L-glutamine on Tobacco Use Week 24 · YES - Tobacco use	2 Participants	1 Participants
Effect of L-glutamine on Tobacco Use Week 32 · NO - Tobacco use	18 Participants	15 Participants
Effect of L-glutamine on Tobacco Use Week 32 · YES - Tobacco use	1 Participants	0 Participants
Effect of L-glutamine on Tobacco Use Week 40 · NO - Tobacco use	17 Participants	13 Participants
Effect of L-glutamine on Tobacco Use Week 40 · YES - Tobacco use	1 Participants	0 Participants
Effect of L-glutamine on Tobacco Use Week 48 · NO - Tobacco use	16 Participants	12 Participants
Effect of L-glutamine on Tobacco Use Week 48 · YES - Tobacco use	1 Participants	0 Participants

SECONDARY outcome

Timeframe: Weeks 0, 8,16, 24, 32, 40 and 48

Population: The full analysis dataset included all patients who received at least one dose of study medication and had been diagnosed with sickle cell anemia or sickle β°-thalassemia documented by hemoglobin electrophoresis and had at least 2 episodes of painful crises within 12 months prior to the screening visit (N = 62)

Percentage of days a patient's daily activities were interrupted due to sickle pain calculated at each visit. Day's interrupted will be reported at Weeks 0, 8,16, 24, 32, 40 and 48

Outcome measures

Measure	Investigational Product n=33 Participants L-glutamine L-glutamine: Approximately 0.3 g/kg total daily dose of L-glutamine will be orally administered (over two doses), with a maximum total daily dose of 30 grams.	Placebo n=29 Participants maltodextrin Placebo: Approximately 0.3 g/kg total daily dose of maltodextrin placebo will be orally administered (over two doses), with a maximum total daily dose of 30 grams.
The Effect of Oral L-glutamine on the Number of Days Patient's Daily Activities Are Interrupted Due to Sickle Cell Pain Week 24	11.4 % of days interrupted Standard Deviation 18.34	11.7 % of days interrupted Standard Deviation 12.75
The Effect of Oral L-glutamine on the Number of Days Patient's Daily Activities Are Interrupted Due to Sickle Cell Pain Week 0	8.3 % of days interrupted Standard Deviation 11.19	8.1 % of days interrupted Standard Deviation 11.94
The Effect of Oral L-glutamine on the Number of Days Patient's Daily Activities Are Interrupted Due to Sickle Cell Pain Week 8	11.9 % of days interrupted Standard Deviation 21.22	24.2 % of days interrupted Standard Deviation 29.22
The Effect of Oral L-glutamine on the Number of Days Patient's Daily Activities Are Interrupted Due to Sickle Cell Pain Week 16	23.3 % of days interrupted Standard Deviation 28.56	15.5 % of days interrupted Standard Deviation 21.55
The Effect of Oral L-glutamine on the Number of Days Patient's Daily Activities Are Interrupted Due to Sickle Cell Pain Week 32	12.5 % of days interrupted Standard Deviation 17.96	15.7 % of days interrupted Standard Deviation 17.33
The Effect of Oral L-glutamine on the Number of Days Patient's Daily Activities Are Interrupted Due to Sickle Cell Pain Week 40	13.2 % of days interrupted Standard Deviation 16.88	28.0 % of days interrupted Standard Deviation 31.33
The Effect of Oral L-glutamine on the Number of Days Patient's Daily Activities Are Interrupted Due to Sickle Cell Pain Week 48	11.7 % of days interrupted Standard Deviation 19.17	11.5 % of days interrupted Standard Deviation 17.58

SECONDARY outcome

Timeframe: Baseline and Week 24 (or at time of discontinuation)

Population: The full analysis dataset included all patients who received at least one dose of study medication and had been diagnosed with sickle cell anemia or sickle β°-thalassemia documented by hemoglobin electrophoresis and had at least 2 episodes of painful crises within 12 months prior to the screening visit (N = 62)

The subjective quality of life was evaluated using the scoring of the RAND 36-Item Health Survey Questionnaire. The subjective quality of life (Physical functioning, Physical health, Emotional problems, Energy/Fatigue, Emotional well being, Social functioning, Pain, General health) will be reported at Baseline and Week 24 (or at time of discontinuation). The range for Physical functioning, Physical health, Emotional problems, Emotional well being and Social functioning is 0-100, with a high score denotes a better quality of life. For Energy/Fatigue, Pain and General health the range is 0-100, with a lower score denotes better quality of life.

Outcome measures

Measure	Investigational Product n=33 Participants L-glutamine L-glutamine: Approximately 0.3 g/kg total daily dose of L-glutamine will be orally administered (over two doses), with a maximum total daily dose of 30 grams.	Placebo n=29 Participants maltodextrin Placebo: Approximately 0.3 g/kg total daily dose of maltodextrin placebo will be orally administered (over two doses), with a maximum total daily dose of 30 grams.
The Effect of Oral L-glutamine on Subjective Quality of Life Physical Functioning Baseline	61.7 score on a scale Standard Deviation 25.38	69.9 score on a scale Standard Deviation 26.68
The Effect of Oral L-glutamine on Subjective Quality of Life Physical Functioning Week 24	65.5 score on a scale Standard Deviation 23.18	76.0 score on a scale Standard Deviation 17.38
The Effect of Oral L-glutamine on Subjective Quality of Life Physical Health - Baseline	43.5 score on a scale Standard Deviation 38.17	49.1 score on a scale Standard Deviation 40.72
The Effect of Oral L-glutamine on Subjective Quality of Life Physical Health - Week 24	55.6 score on a scale Standard Deviation 41.79	46.7 score on a scale Standard Deviation 40.83
The Effect of Oral L-glutamine on Subjective Quality of Life Emotional Problems - Baseline	52.7 score on a scale Standard Deviation 41.97	66.7 score on a scale Standard Deviation 41.35
The Effect of Oral L-glutamine on Subjective Quality of Life Emotional Problems - Week 24	58.3 score on a scale Standard Deviation 40.20	65.3 score on a scale Standard Deviation 40.24
The Effect of Oral L-glutamine on Subjective Quality of Life Energy/Fatigue - Baseline	45.7 score on a scale Standard Deviation 12.29	50.0 score on a scale Standard Deviation 17.82
The Effect of Oral L-glutamine on Subjective Quality of Life Energy/Fatigue - Week 24	49.8 score on a scale Standard Deviation 19.65	53.4 score on a scale Standard Deviation 21.96
The Effect of Oral L-glutamine on Subjective Quality of Life Emotional Well Being - Baseline	66.2 score on a scale Standard Deviation 19.37	74.5 score on a scale Standard Deviation 16.02
The Effect of Oral L-glutamine on Subjective Quality of Life Emotional Well Being - Week 24	71.9 score on a scale Standard Deviation 17.83	77.1 score on a scale Standard Deviation 21.92
The Effect of Oral L-glutamine on Subjective Quality of Life Social Functioning - Baseline	61.3 score on a scale Standard Deviation 24.01	62.5 score on a scale Standard Deviation 24.27
The Effect of Oral L-glutamine on Subjective Quality of Life Social Functioning - Week 24	72.5 score on a scale Standard Deviation 22.06	65.6 score on a scale Standard Deviation 26.02
The Effect of Oral L-glutamine on Subjective Quality of Life Pain - Baseline	53.4 score on a scale Standard Deviation 23.41	55.5 score on a scale Standard Deviation 28.07
The Effect of Oral L-glutamine on Subjective Quality of Life Pain - Week 24	59.1 score on a scale Standard Deviation 24.60	56.1 score on a scale Standard Deviation 30.76
The Effect of Oral L-glutamine on Subjective Quality of Life General Health - Baseline	46.0 score on a scale Standard Deviation 17.42	49.7 score on a scale Standard Deviation 21.5
The Effect of Oral L-glutamine on Subjective Quality of Life General Health - Week 24	53.9 score on a scale Standard Deviation 16.55	57.0 score on a scale Standard Deviation 18.62

SECONDARY outcome

Timeframe: Baseline, Weeks 4, 24, and 48

Population: The full analysis dataset included all patients who received at least one dose of study medication and had been diagnosed with sickle cell anemia or sickle β°-thalassemia documented by hemoglobin electrophoresis and had at least 2 episodes of painful crises within 12 months prior to the screening visit (N = 62)

Height will be measured at each visit. Change from Baseline will be reported at Weeks 4, 24, and 48

Outcome measures

Measure	Investigational Product n=33 Participants L-glutamine L-glutamine: Approximately 0.3 g/kg total daily dose of L-glutamine will be orally administered (over two doses), with a maximum total daily dose of 30 grams.	Placebo n=29 Participants maltodextrin Placebo: Approximately 0.3 g/kg total daily dose of maltodextrin placebo will be orally administered (over two doses), with a maximum total daily dose of 30 grams.
Effect of Oral L--glutamine on Height Change in Height at Week 48	-1.7 cm Standard Deviation 6.58	0.4 cm Standard Deviation 3.35
Effect of Oral L--glutamine on Height Baseline	169.8 cm Standard Deviation 9.49	169.2 cm Standard Deviation 11.87
Effect of Oral L--glutamine on Height Change in Height at Week 4	-0.1 cm Standard Deviation 1.18	0.2 cm Standard Deviation 2.87
Effect of Oral L--glutamine on Height Change in Height at Week 24	0.1 cm Standard Deviation 1.54	-0.1 cm Standard Deviation 1.68

SECONDARY outcome

Timeframe: Baseline, Weeks 4, 24 and 48

Population: The full analysis dataset included all patients who received at least one dose of study medication and had been diagnosed with sickle cell anemia or sickle β°-thalassemia documented by hemoglobin electrophoresis and had at least 2 episodes of painful crises within 12 months prior to the screening visit (N = 62)

Weight will be measured at each visit. Change from Baseline will be reported at Weeks 4, 24, and 48

Outcome measures

Measure	Investigational Product n=33 Participants L-glutamine L-glutamine: Approximately 0.3 g/kg total daily dose of L-glutamine will be orally administered (over two doses), with a maximum total daily dose of 30 grams.	Placebo n=29 Participants maltodextrin Placebo: Approximately 0.3 g/kg total daily dose of maltodextrin placebo will be orally administered (over two doses), with a maximum total daily dose of 30 grams.
Effect of Oral L--glutamine on Weight Baseline	67.1 kg Standard Deviation 13.39	70.7 kg Standard Deviation 18.20
Effect of Oral L--glutamine on Weight Change in Weight at Week 4	0.8 kg Standard Deviation 1.89	0.1 kg Standard Deviation 3.13
Effect of Oral L--glutamine on Weight Change in Weight at Week 24	1.2 kg Standard Deviation 2.55	1.4 kg Standard Deviation 5.04
Effect of Oral L--glutamine on Weight Change in Weight at Week 48	-1.0 kg Standard Deviation 10.79	1.9 kg Standard Deviation 7.39

SECONDARY outcome

Timeframe: Baseline, Weeks 4, 24, and 48.

Population: The full analysis dataset included all patients who received at least one dose of study medication and had been diagnosed with sickle cell anemia or sickle β°-thalassemia documented by hemoglobin electrophoresis and had at least 2 episodes of painful crises within 12 months prior to the screening visit (N = 62)

Minutes patient could walk without rest will be measured at each visit. Change from Baseline will be reported at Weeks 4, 24, and 48.

Outcome measures

Measure	Investigational Product n=33 Participants L-glutamine L-glutamine: Approximately 0.3 g/kg total daily dose of L-glutamine will be orally administered (over two doses), with a maximum total daily dose of 30 grams.	Placebo n=29 Participants maltodextrin Placebo: Approximately 0.3 g/kg total daily dose of maltodextrin placebo will be orally administered (over two doses), with a maximum total daily dose of 30 grams.
Effect of L-glutamine on Subjective Exercise Tolerance - Minutes Patient Could Walk Without Rest Change in Minutes patient could walk without rest at Week 24	-1.9 mins Standard Deviation 26.30	-3.5 mins Standard Deviation 12.63
Effect of L-glutamine on Subjective Exercise Tolerance - Minutes Patient Could Walk Without Rest Baseline - Minutes patient could walk without rest	32 mins Standard Deviation 28.25	28.6 mins Standard Deviation 23.94
Effect of L-glutamine on Subjective Exercise Tolerance - Minutes Patient Could Walk Without Rest Change in Minutes patient could walk without rest at Week 4	-2.1 mins Standard Deviation 29.57	-1.8 mins Standard Deviation 20.06
Effect of L-glutamine on Subjective Exercise Tolerance - Minutes Patient Could Walk Without Rest Change in Minutes patient could walk without rest at Week 48	-5.8 mins Standard Deviation 24.88	6.7 mins Standard Deviation 28.95

SECONDARY outcome

Timeframe: Baseline, Weeks 4, 24, and 48.

Population: The full analysis dataset included all patients who received at least one dose of study medication and had been diagnosed with sickle cell anemia or sickle β°-thalassemia documented by hemoglobin electrophoresis and had at least 2 episodes of painful crises within 12 months prior to the screening visit (N = 62)

Minutes patient could run without rest will be measured at each visit. Change from Baseline will be reported at Weeks 4, 24, and 48.

Outcome measures

Measure	Investigational Product n=33 Participants L-glutamine L-glutamine: Approximately 0.3 g/kg total daily dose of L-glutamine will be orally administered (over two doses), with a maximum total daily dose of 30 grams.	Placebo n=29 Participants maltodextrin Placebo: Approximately 0.3 g/kg total daily dose of maltodextrin placebo will be orally administered (over two doses), with a maximum total daily dose of 30 grams.
Effect of L-glutamine on Subjective Exercise Tolerance - Minutes Patient Could Run Without Rest Baseline - Minutes patient could run without rest	5.1 mins Standard Deviation 8.90	7.4 mins Standard Deviation 10.02
Effect of L-glutamine on Subjective Exercise Tolerance - Minutes Patient Could Run Without Rest Change in Minutes patient could run without rest at Week 4	-0.7 mins Standard Deviation 4.75	-0.7 mins Standard Deviation 8.64
Effect of L-glutamine on Subjective Exercise Tolerance - Minutes Patient Could Run Without Rest Change in Minutes patient could run without rest at Week 24	-0.3 mins Standard Deviation 5.17	-1.2 mins Standard Deviation 13.56
Effect of L-glutamine on Subjective Exercise Tolerance - Minutes Patient Could Run Without Rest Change in Minutes patient could run without rest at Week 48	-0.8 mins Standard Deviation 5.14	-1.2 mins Standard Deviation 12.78

SECONDARY outcome

Timeframe: Baseline, Weeks 4, 24, and 48.

Population: The full analysis dataset included all patients who received at least one dose of study medication and had been diagnosed with sickle cell anemia or sickle β°-thalassemia documented by hemoglobin electrophoresis and had at least 2 episodes of painful crises within 12 months prior to the screening visit (N = 62)

Distance patient could walk without rest will be collected at each visit. Change from Baseline will be reported at Weeks 4, 24, and 48.

Outcome measures

Measure	Investigational Product n=33 Participants L-glutamine L-glutamine: Approximately 0.3 g/kg total daily dose of L-glutamine will be orally administered (over two doses), with a maximum total daily dose of 30 grams.	Placebo n=29 Participants maltodextrin Placebo: Approximately 0.3 g/kg total daily dose of maltodextrin placebo will be orally administered (over two doses), with a maximum total daily dose of 30 grams.
Effect of L-glutamine on Subjective Exercise Tolerance - Distance Patient Could Walk Without Rest Baseline - Distance patient could walk without rest	4097.5 feet Standard Deviation 2739	5680.7 feet Standard Deviation 7695
Effect of L-glutamine on Subjective Exercise Tolerance - Distance Patient Could Walk Without Rest Change in Distance patient could walk without rest at Week 4	41.9 feet Standard Deviation 1976	302.5 feet Standard Deviation 2022
Effect of L-glutamine on Subjective Exercise Tolerance - Distance Patient Could Walk Without Rest Change in Distance patient could walk without rest at Week 24	74.5 feet Standard Deviation 2116	-1719 feet Standard Deviation 9569
Effect of L-glutamine on Subjective Exercise Tolerance - Distance Patient Could Walk Without Rest Change in Distance patient could walk without rest at Week 48	38.8 feet Standard Deviation 2766	-4240 feet Standard Deviation 11782

SECONDARY outcome

Timeframe: Baseline, Weeks 4, 24, and 48.

Population: The full analysis dataset included all patients who received at least one dose of study medication and had been diagnosed with sickle cell anemia or sickle β°-thalassemia documented by hemoglobin electrophoresis and had at least 2 episodes of painful crises within 12 months prior to the screening visit (N = 62)

Distance patient could run without rest will be collected at each visit. Change from Baseline will be reported at Weeks 4, 24, and 48.

Outcome measures

Measure	Investigational Product n=33 Participants L-glutamine L-glutamine: Approximately 0.3 g/kg total daily dose of L-glutamine will be orally administered (over two doses), with a maximum total daily dose of 30 grams.	Placebo n=29 Participants maltodextrin Placebo: Approximately 0.3 g/kg total daily dose of maltodextrin placebo will be orally administered (over two doses), with a maximum total daily dose of 30 grams.
Effect of L-glutamine on Subjective Exercise Tolerance - Distance Patient Could Run Without Rest Baseline - Distance patient could run without rest	1059.5 feet Standard Deviation 1688	1482.1 feet Standard Deviation 2160
Effect of L-glutamine on Subjective Exercise Tolerance - Distance Patient Could Run Without Rest Change in Distance patient could run without rest at Week 4	-31.6 feet Standard Deviation 1054	124.2 feet Standard Deviation 1226
Effect of L-glutamine on Subjective Exercise Tolerance - Distance Patient Could Run Without Rest Change in Distance patient could run without rest at Week 24	215.9 feet Standard Deviation 1411	186.5 feet Standard Deviation 2901
Effect of L-glutamine on Subjective Exercise Tolerance - Distance Patient Could Run Without Rest Change in Distance patient could run without rest at Week 48	13.5 feet Standard Deviation 1677	-586.7 feet Standard Deviation 2698

Adverse Events

Investigational Product

Serious events: 24 serious events

Other events: 37 other events

Deaths: 1 deaths

Placebo

Serious events: 21 serious events

Other events: 33 other events

Deaths: 0 deaths

Serious adverse events

Measure	Investigational Product n=37 participants at risk L-glutamine L-glutamine: Approximately 0.3 g/kg total daily dose of L-glutamine will be orally administered (over two doses), with a maximum total daily dose of 30 grams.	Placebo n=33 participants at risk maltodextrin Placebo: Approximately 0.3 g/kg total daily dose of maltodextrin placebo will be orally administered (over two doses), with a maximum total daily dose of 30 grams.
Congenital, familial and genetic disorders Sickle cell anaemia with crisis	59.5% 22/37 • Number of events 22 • Adverse events data were collected throughout the course of the study (53 weeks or about 1 year). The Safety population will include all patients who received at least one dose of study medication.	51.5% 17/33 • Number of events 17 • Adverse events data were collected throughout the course of the study (53 weeks or about 1 year). The Safety population will include all patients who received at least one dose of study medication.
Cardiac disorders Palpitations	0.00% 0/37 • Adverse events data were collected throughout the course of the study (53 weeks or about 1 year). The Safety population will include all patients who received at least one dose of study medication.	3.0% 1/33 • Number of events 1 • Adverse events data were collected throughout the course of the study (53 weeks or about 1 year). The Safety population will include all patients who received at least one dose of study medication.
General disorders pyrexia	0.00% 0/37 • Adverse events data were collected throughout the course of the study (53 weeks or about 1 year). The Safety population will include all patients who received at least one dose of study medication.	3.0% 1/33 • Number of events 1 • Adverse events data were collected throughout the course of the study (53 weeks or about 1 year). The Safety population will include all patients who received at least one dose of study medication.
Infections and infestations Pneumonia	8.1% 3/37 • Number of events 3 • Adverse events data were collected throughout the course of the study (53 weeks or about 1 year). The Safety population will include all patients who received at least one dose of study medication.	3.0% 1/33 • Number of events 1 • Adverse events data were collected throughout the course of the study (53 weeks or about 1 year). The Safety population will include all patients who received at least one dose of study medication.
Infections and infestations URTI	0.00% 0/37 • Adverse events data were collected throughout the course of the study (53 weeks or about 1 year). The Safety population will include all patients who received at least one dose of study medication.	3.0% 1/33 • Number of events 1 • Adverse events data were collected throughout the course of the study (53 weeks or about 1 year). The Safety population will include all patients who received at least one dose of study medication.
Investigations Blood potassium increased	2.7% 1/37 • Number of events 1 • Adverse events data were collected throughout the course of the study (53 weeks or about 1 year). The Safety population will include all patients who received at least one dose of study medication.	0.00% 0/33 • Adverse events data were collected throughout the course of the study (53 weeks or about 1 year). The Safety population will include all patients who received at least one dose of study medication.
Metabolism and nutrition disorders Hypoglycaemia	2.7% 1/37 • Number of events 1 • Adverse events data were collected throughout the course of the study (53 weeks or about 1 year). The Safety population will include all patients who received at least one dose of study medication.	0.00% 0/33 • Adverse events data were collected throughout the course of the study (53 weeks or about 1 year). The Safety population will include all patients who received at least one dose of study medication.
Pregnancy, puerperium and perinatal conditions Pregnancy	5.4% 2/37 • Number of events 2 • Adverse events data were collected throughout the course of the study (53 weeks or about 1 year). The Safety population will include all patients who received at least one dose of study medication.	3.0% 1/33 • Number of events 1 • Adverse events data were collected throughout the course of the study (53 weeks or about 1 year). The Safety population will include all patients who received at least one dose of study medication.
Renal and urinary disorders Renal failure acute	2.7% 1/37 • Number of events 1 • Adverse events data were collected throughout the course of the study (53 weeks or about 1 year). The Safety population will include all patients who received at least one dose of study medication.	0.00% 0/33 • Adverse events data were collected throughout the course of the study (53 weeks or about 1 year). The Safety population will include all patients who received at least one dose of study medication.
Reproductive system and breast disorders Priapism	0.00% 0/37 • Adverse events data were collected throughout the course of the study (53 weeks or about 1 year). The Safety population will include all patients who received at least one dose of study medication.	3.0% 1/33 • Number of events 1 • Adverse events data were collected throughout the course of the study (53 weeks or about 1 year). The Safety population will include all patients who received at least one dose of study medication.
Respiratory, thoracic and mediastinal disorders Asthma	0.00% 0/37 • Adverse events data were collected throughout the course of the study (53 weeks or about 1 year). The Safety population will include all patients who received at least one dose of study medication.	6.1% 2/33 • Number of events 2 • Adverse events data were collected throughout the course of the study (53 weeks or about 1 year). The Safety population will include all patients who received at least one dose of study medication.
Surgical and medical procedures Hip Arthroplasty	0.00% 0/37 • Adverse events data were collected throughout the course of the study (53 weeks or about 1 year). The Safety population will include all patients who received at least one dose of study medication.	3.0% 1/33 • Number of events 1 • Adverse events data were collected throughout the course of the study (53 weeks or about 1 year). The Safety population will include all patients who received at least one dose of study medication.

Other adverse events

Measure	Investigational Product n=37 participants at risk L-glutamine L-glutamine: Approximately 0.3 g/kg total daily dose of L-glutamine will be orally administered (over two doses), with a maximum total daily dose of 30 grams.	Placebo n=33 participants at risk maltodextrin Placebo: Approximately 0.3 g/kg total daily dose of maltodextrin placebo will be orally administered (over two doses), with a maximum total daily dose of 30 grams.
Congenital, familial and genetic disorders Sickle cell anemia with crisis	83.8% 31/37 • Number of events 31 • Adverse events data were collected throughout the course of the study (53 weeks or about 1 year). The Safety population will include all patients who received at least one dose of study medication.	78.8% 26/33 • Number of events 26 • Adverse events data were collected throughout the course of the study (53 weeks or about 1 year). The Safety population will include all patients who received at least one dose of study medication.
Gastrointestinal disorders Diarrhea	8.1% 3/37 • Number of events 3 • Adverse events data were collected throughout the course of the study (53 weeks or about 1 year). The Safety population will include all patients who received at least one dose of study medication.	3.0% 1/33 • Number of events 1 • Adverse events data were collected throughout the course of the study (53 weeks or about 1 year). The Safety population will include all patients who received at least one dose of study medication.
Gastrointestinal disorders Abdominal pain upper	5.4% 2/37 • Number of events 2 • Adverse events data were collected throughout the course of the study (53 weeks or about 1 year). The Safety population will include all patients who received at least one dose of study medication.	6.1% 2/33 • Number of events 2 • Adverse events data were collected throughout the course of the study (53 weeks or about 1 year). The Safety population will include all patients who received at least one dose of study medication.
Gastrointestinal disorders Constipation	5.4% 2/37 • Number of events 2 • Adverse events data were collected throughout the course of the study (53 weeks or about 1 year). The Safety population will include all patients who received at least one dose of study medication.	3.0% 1/33 • Number of events 1 • Adverse events data were collected throughout the course of the study (53 weeks or about 1 year). The Safety population will include all patients who received at least one dose of study medication.
Gastrointestinal disorders Toothache	5.4% 2/37 • Number of events 2 • Adverse events data were collected throughout the course of the study (53 weeks or about 1 year). The Safety population will include all patients who received at least one dose of study medication.	0.00% 0/33 • Adverse events data were collected throughout the course of the study (53 weeks or about 1 year). The Safety population will include all patients who received at least one dose of study medication.
General disorders Chest pain	5.4% 2/37 • Number of events 2 • Adverse events data were collected throughout the course of the study (53 weeks or about 1 year). The Safety population will include all patients who received at least one dose of study medication.	0.00% 0/33 • Adverse events data were collected throughout the course of the study (53 weeks or about 1 year). The Safety population will include all patients who received at least one dose of study medication.
General disorders Influenza-like illness	0.00% 0/37 • Adverse events data were collected throughout the course of the study (53 weeks or about 1 year). The Safety population will include all patients who received at least one dose of study medication.	6.1% 2/33 • Number of events 2 • Adverse events data were collected throughout the course of the study (53 weeks or about 1 year). The Safety population will include all patients who received at least one dose of study medication.
Infections and infestations Pneumonia	10.8% 4/37 • Number of events 4 • Adverse events data were collected throughout the course of the study (53 weeks or about 1 year). The Safety population will include all patients who received at least one dose of study medication.	3.0% 1/33 • Number of events 1 • Adverse events data were collected throughout the course of the study (53 weeks or about 1 year). The Safety population will include all patients who received at least one dose of study medication.
Infections and infestations Nasopharyngitis	8.1% 3/37 • Number of events 3 • Adverse events data were collected throughout the course of the study (53 weeks or about 1 year). The Safety population will include all patients who received at least one dose of study medication.	9.1% 3/33 • Number of events 3 • Adverse events data were collected throughout the course of the study (53 weeks or about 1 year). The Safety population will include all patients who received at least one dose of study medication.
Infections and infestations Gastroenteritis	5.4% 2/37 • Number of events 2 • Adverse events data were collected throughout the course of the study (53 weeks or about 1 year). The Safety population will include all patients who received at least one dose of study medication.	15.2% 5/33 • Number of events 5 • Adverse events data were collected throughout the course of the study (53 weeks or about 1 year). The Safety population will include all patients who received at least one dose of study medication.
Infections and infestations URTI	2.7% 1/37 • Number of events 1 • Adverse events data were collected throughout the course of the study (53 weeks or about 1 year). The Safety population will include all patients who received at least one dose of study medication.	9.1% 3/33 • Number of events 3 • Adverse events data were collected throughout the course of the study (53 weeks or about 1 year). The Safety population will include all patients who received at least one dose of study medication.
Infections and infestations Ear infection	0.00% 0/37 • Adverse events data were collected throughout the course of the study (53 weeks or about 1 year). The Safety population will include all patients who received at least one dose of study medication.	6.1% 2/33 • Number of events 2 • Adverse events data were collected throughout the course of the study (53 weeks or about 1 year). The Safety population will include all patients who received at least one dose of study medication.
Infections and infestations Gastroentritis viral	0.00% 0/37 • Adverse events data were collected throughout the course of the study (53 weeks or about 1 year). The Safety population will include all patients who received at least one dose of study medication.	6.1% 2/33 • Number of events 2 • Adverse events data were collected throughout the course of the study (53 weeks or about 1 year). The Safety population will include all patients who received at least one dose of study medication.
Musculoskeletal and connective tissue disorders Arthralgia	5.4% 2/37 • Number of events 2 • Adverse events data were collected throughout the course of the study (53 weeks or about 1 year). The Safety population will include all patients who received at least one dose of study medication.	21.2% 7/33 • Number of events 7 • Adverse events data were collected throughout the course of the study (53 weeks or about 1 year). The Safety population will include all patients who received at least one dose of study medication.
Musculoskeletal and connective tissue disorders Back pain	5.4% 2/37 • Number of events 2 • Adverse events data were collected throughout the course of the study (53 weeks or about 1 year). The Safety population will include all patients who received at least one dose of study medication.	6.1% 2/33 • Number of events 2 • Adverse events data were collected throughout the course of the study (53 weeks or about 1 year). The Safety population will include all patients who received at least one dose of study medication.
Nervous system disorders Headache	8.1% 3/37 • Number of events 3 • Adverse events data were collected throughout the course of the study (53 weeks or about 1 year). The Safety population will include all patients who received at least one dose of study medication.	9.1% 3/33 • Number of events 3 • Adverse events data were collected throughout the course of the study (53 weeks or about 1 year). The Safety population will include all patients who received at least one dose of study medication.
Nervous system disorders Convulsion	5.4% 2/37 • Number of events 2 • Adverse events data were collected throughout the course of the study (53 weeks or about 1 year). The Safety population will include all patients who received at least one dose of study medication.	0.00% 0/33 • Adverse events data were collected throughout the course of the study (53 weeks or about 1 year). The Safety population will include all patients who received at least one dose of study medication.
Pregnancy, puerperium and perinatal conditions Pregnancy	5.4% 2/37 • Number of events 2 • Adverse events data were collected throughout the course of the study (53 weeks or about 1 year). The Safety population will include all patients who received at least one dose of study medication.	3.0% 1/33 • Number of events 1 • Adverse events data were collected throughout the course of the study (53 weeks or about 1 year). The Safety population will include all patients who received at least one dose of study medication.
Respiratory, thoracic and mediastinal disorders Cough	5.4% 2/37 • Number of events 2 • Adverse events data were collected throughout the course of the study (53 weeks or about 1 year). The Safety population will include all patients who received at least one dose of study medication.	0.00% 0/33 • Adverse events data were collected throughout the course of the study (53 weeks or about 1 year). The Safety population will include all patients who received at least one dose of study medication.
Respiratory, thoracic and mediastinal disorders Asthma	0.00% 0/37 • Adverse events data were collected throughout the course of the study (53 weeks or about 1 year). The Safety population will include all patients who received at least one dose of study medication.	6.1% 2/33 • Number of events 2 • Adverse events data were collected throughout the course of the study (53 weeks or about 1 year). The Safety population will include all patients who received at least one dose of study medication.

Additional Information

Yutaka Niihara, MD, MPH

Emmaus Medical, Inc.

Phone: 310-214-0065

Email: yniihara@emmausmedical.com

Results disclosure agreements

• Principal investigator is a sponsor employee PI agrees that any INFORMATION submitted to it by EMMAUS shall be maintained in secrecy for a period of seven (7) years from each disclosure of INFORMATION. PI will use the up most due diligence to prevent disclosure by it except to its employees, agents, and contractors necessary for evaluation, all of whom shall be bound by similar written obligations of confidentiality, and who agree not to use the INFORMATION for any purpose other than for evaluation purposes.
• Publication restrictions are in place

Restriction type: OTHER