Trial Outcomes & Findings for Evaluation of Different Dose Regimens of Aes-103 Given for 28 Days to Subjects With Stable Sickle Cell Disease (NCT NCT01987908)

NCT ID: NCT01987908

Last Updated: 2021-05-25

Results Overview

Number of participants with adverse events (AEs) reported during the double-blind treatment period. AEs included clinically-significant changes in vital signs, ECG, clinical laboratory assessments, physical and neurological examinations. Sickle cell-specific symptoms included the development of new skin ulcers, hospitalization or ambulatory acute care, intravenous analgesics visit for pain episodes (i.e., sickle-cell disease related pain), acute chest syndrome, priapism, and stroke.

• Recruitment status: TERMINATED
• Study phase: PHASE2
• Target enrollment: 35 participants
• Primary outcome timeframe: Double-blind treatment period of 28 days (Day 1 to Day 28)
• Results posted on: 2021-05-25

Participant Flow

Enrollment was conducted at one clinical site in the United Kingdom with referrals and/or patient identification from five other clinical sites in the United Kingdom.

35 participants were enrolled. 10 failed screen and 2 were randomization failures. 23 started the 2-week, single-blind, placebo lead-in period (to obtain stable baseline values and to screen out participants who did not tolerate placebo or were not compliant with study procedures).

Participant milestones

Measure	Placebo lead-in Period Participants enrolled in a 14 day single-blind placebo lead-in received 4 times daily dosing of placebo	Treatment With Study Product After placebo lead-in period, participants randomized 3:1 (Aes-103 to placebo) to receive 4 times daily dosing of 1,000 mg of Aes-103 for 28 days during the double-blind treatment period	Treatment With Placebo After placebo lead-in period, participants randomized 3:1 (Aes-103 to placebo) to receive 4 times daily dosing of 1,000 mg of placebo for 28 days during the double-blind treatment period
Placebo Lead-in Period STARTED	23	0	0
Placebo Lead-in Period COMPLETED	14	0	0
Placebo Lead-in Period NOT COMPLETED	9	0	0
Treatment Period STARTED	0	11	3
Treatment Period COMPLETED	0	10	2
Treatment Period NOT COMPLETED	0	1	1
Post-Treatment Observation Period STARTED	0	10	2
Post-Treatment Observation Period COMPLETED	0	7	2
Post-Treatment Observation Period NOT COMPLETED	0	3	0

Reasons for withdrawal

Measure	Placebo lead-in Period Participants enrolled in a 14 day single-blind placebo lead-in received 4 times daily dosing of placebo	Treatment With Study Product After placebo lead-in period, participants randomized 3:1 (Aes-103 to placebo) to receive 4 times daily dosing of 1,000 mg of Aes-103 for 28 days during the double-blind treatment period	Treatment With Placebo After placebo lead-in period, participants randomized 3:1 (Aes-103 to placebo) to receive 4 times daily dosing of 1,000 mg of placebo for 28 days during the double-blind treatment period
Placebo Lead-in Period Adverse Event	2	0	0
Placebo Lead-in Period Physician Decision	2	0	0
Placebo Lead-in Period Withdrawal by Subject	1	0	0
Placebo Lead-in Period Other: Study Termination by Sponsor	4	0	0
Treatment Period Adverse Event	0	1	1
Post-Treatment Observation Period Other: Study Termination by Sponsor	0	2	0
Post-Treatment Observation Period Other: Bad Veins	0	1	0

Baseline Characteristics

Evaluation of Different Dose Regimens of Aes-103 Given for 28 Days to Subjects With Stable Sickle Cell Disease

Baseline characteristics by cohort

Measure	Placebo lead-in Period n=23 Participants Participants enrolled in a 14 day single-blind placebo lead-in received 4 times daily dosing of placebo
Age, Continuous	28 Years STANDARD_DEVIATION 7 • n=93 Participants
Sex: Female, Male Female	13 Participants n=93 Participants
Sex: Female, Male Male	10 Participants n=93 Participants

PRIMARY outcome

Timeframe: Double-blind treatment period of 28 days (Day 1 to Day 28)

Number of participants with adverse events (AEs) reported during the double-blind treatment period. AEs included clinically-significant changes in vital signs, ECG, clinical laboratory assessments, physical and neurological examinations. Sickle cell-specific symptoms included the development of new skin ulcers, hospitalization or ambulatory acute care, intravenous analgesics visit for pain episodes (i.e., sickle-cell disease related pain), acute chest syndrome, priapism, and stroke.

Outcome measures

Measure	Treatment With Study Product n=11 Participants Participants randomized 3:1 (Aes-103 to placebo) to receive 4 times daily dosing of 1,000 mg of Aes-103 for 28 days	Treatment With Placebo n=3 Participants Participants randomized 3:1 (Aes-103 to placebo) to receive 4 times daily dosing of 1,000 mg of placebo for 28 days	All Treated Participants n=14 Participants All participants randomized 3:1 (Aes-103 to placebo) and received 4 times daily dosing of 1,000 mg AEs-103 or 1,000 mg of placebo for 28 days	Post-treatment With Study Product Observation Period Participants underwent a post-treatment observation period of 21 days during which no study product (Aes-103) was received	Post-treatment With Placebo Observation Period Participants underwent a post-treatment observation period of 21 days during which no placebo was received
Number of Participants With Adverse Events, Including Sickle Cell-specific Symptoms, During the Double-blind Treatment Period AEs leading to discontinuation	1 participants	1 participants	2 participants	—	—
Number of Participants With Adverse Events, Including Sickle Cell-specific Symptoms, During the Double-blind Treatment Period AEs leading to death	0 participants	0 participants	0 participants	—	—
Number of Participants With Adverse Events, Including Sickle Cell-specific Symptoms, During the Double-blind Treatment Period Sickle-cell specific complications	4 participants	1 participants	5 participants	—	—
Number of Participants With Adverse Events, Including Sickle Cell-specific Symptoms, During the Double-blind Treatment Period Treatment-emergent AEs	9 participants	3 participants	12 participants	—	—
Number of Participants With Adverse Events, Including Sickle Cell-specific Symptoms, During the Double-blind Treatment Period Related AEs	8 participants	2 participants	10 participants	—	—
Number of Participants With Adverse Events, Including Sickle Cell-specific Symptoms, During the Double-blind Treatment Period Serious AEs	0 participants	0 participants	0 participants	—	—
Number of Participants With Adverse Events, Including Sickle Cell-specific Symptoms, During the Double-blind Treatment Period Severe AEs	0 participants	0 participants	0 participants	—	—

PRIMARY outcome

Timeframe: Placebo lead-in period of 14 days (Day -14 to Day -1)

Number of participants with adverse events (AEs) reported during the placebo lead-in period. AEs included clinically-significant changes in vital signs, ECG, clinical laboratory assessments, physical and neurological examinations. Sickle cell-specific symptoms included the development of new skin ulcers, hospitalization or ambulatory acute care, intravenous analgesics visit for pain episodes (i.e., sickle-cell disease related pain), acute chest syndrome, priapism, and stroke.

Outcome measures

Measure	Treatment With Study Product n=23 Participants Participants randomized 3:1 (Aes-103 to placebo) to receive 4 times daily dosing of 1,000 mg of Aes-103 for 28 days	Treatment With Placebo Participants randomized 3:1 (Aes-103 to placebo) to receive 4 times daily dosing of 1,000 mg of placebo for 28 days	All Treated Participants All participants randomized 3:1 (Aes-103 to placebo) and received 4 times daily dosing of 1,000 mg AEs-103 or 1,000 mg of placebo for 28 days	Post-treatment With Study Product Observation Period Participants underwent a post-treatment observation period of 21 days during which no study product (Aes-103) was received	Post-treatment With Placebo Observation Period Participants underwent a post-treatment observation period of 21 days during which no placebo was received
Number of Participants With Adverse Events, Including Sickle-cell Specific Symptoms, During the Placebo lead-in Period Treatment-emergent AEs	21 participants	—	—	—	—
Number of Participants With Adverse Events, Including Sickle-cell Specific Symptoms, During the Placebo lead-in Period Related AEs	12 participants	—	—	—	—
Number of Participants With Adverse Events, Including Sickle-cell Specific Symptoms, During the Placebo lead-in Period Serious AEs	2 participants	—	—	—	—
Number of Participants With Adverse Events, Including Sickle-cell Specific Symptoms, During the Placebo lead-in Period Severe AEs	2 participants	—	—	—	—
Number of Participants With Adverse Events, Including Sickle-cell Specific Symptoms, During the Placebo lead-in Period AEs leading to discontinuation	2 participants	—	—	—	—
Number of Participants With Adverse Events, Including Sickle-cell Specific Symptoms, During the Placebo lead-in Period AEs leading to death	0 participants	—	—	—	—
Number of Participants With Adverse Events, Including Sickle-cell Specific Symptoms, During the Placebo lead-in Period Sickle cell-specific complications	2 participants	—	—	—	—

PRIMARY outcome

Timeframe: Post-treatment observation period of 21 days (Day 29 to Day 49)

Number of participants with adverse events (AEs) reported during the post-treatment observation period. AEs included clinically-significant changes in vital signs, ECG, clinical laboratory assessments, physical and neurological examinations. Sickle cell-specific symptoms included the development of new skin ulcers, hospitalization or ambulatory acute care, intravenous analgesics visit for pain episodes (i.e., sickle-cell disease related pain), acute chest syndrome, priapism, and stroke.

Outcome measures

Measure	Treatment With Study Product n=10 Participants Participants randomized 3:1 (Aes-103 to placebo) to receive 4 times daily dosing of 1,000 mg of Aes-103 for 28 days	Treatment With Placebo n=2 Participants Participants randomized 3:1 (Aes-103 to placebo) to receive 4 times daily dosing of 1,000 mg of placebo for 28 days	All Treated Participants n=12 Participants All participants randomized 3:1 (Aes-103 to placebo) and received 4 times daily dosing of 1,000 mg AEs-103 or 1,000 mg of placebo for 28 days	Post-treatment With Study Product Observation Period Participants underwent a post-treatment observation period of 21 days during which no study product (Aes-103) was received	Post-treatment With Placebo Observation Period Participants underwent a post-treatment observation period of 21 days during which no placebo was received
Number of Participants With Adverse Events, Including Sickle-cell Specific Symptoms, During the Post-treatment Observation Period AEs leading to death	0 participants	0 participants	0 participants	—	—
Number of Participants With Adverse Events, Including Sickle-cell Specific Symptoms, During the Post-treatment Observation Period Sickle cell-specific complications	2 participants	0 participants	2 participants	—	—
Number of Participants With Adverse Events, Including Sickle-cell Specific Symptoms, During the Post-treatment Observation Period Treatment-emergent AEs	4 participants	0 participants	4 participants	—	—
Number of Participants With Adverse Events, Including Sickle-cell Specific Symptoms, During the Post-treatment Observation Period Related AEs	2 participants	0 participants	2 participants	—	—
Number of Participants With Adverse Events, Including Sickle-cell Specific Symptoms, During the Post-treatment Observation Period Serious AEs	1 participants	0 participants	1 participants	—	—
Number of Participants With Adverse Events, Including Sickle-cell Specific Symptoms, During the Post-treatment Observation Period Severe AEs	1 participants	0 participants	1 participants	—	—
Number of Participants With Adverse Events, Including Sickle-cell Specific Symptoms, During the Post-treatment Observation Period AEs leading to discontinuation	0 participants	0 participants	0 participants	—	—

PRIMARY outcome

Timeframe: Placebo lead-in period of 14 days (Day -14 to Day -1), double-blind treatment period of 28 days (Day 1 to Day 28) and post-treatment observation period of 21 days (Day 29 to Day 49)

Outcome measures

Measure	Treatment With Study Product n=23 Participants Participants randomized 3:1 (Aes-103 to placebo) to receive 4 times daily dosing of 1,000 mg of Aes-103 for 28 days	Treatment With Placebo n=11 Participants Participants randomized 3:1 (Aes-103 to placebo) to receive 4 times daily dosing of 1,000 mg of placebo for 28 days	All Treated Participants n=3 Participants All participants randomized 3:1 (Aes-103 to placebo) and received 4 times daily dosing of 1,000 mg AEs-103 or 1,000 mg of placebo for 28 days	Post-treatment With Study Product Observation Period n=10 Participants Participants underwent a post-treatment observation period of 21 days during which no study product (Aes-103) was received	Post-treatment With Placebo Observation Period n=2 Participants Participants underwent a post-treatment observation period of 21 days during which no placebo was received
Number of Participants With Sickle-Cell Disease-related Symptoms Abdominal Pain - Sickle Pain	0 participants	1 participants	0 participants	0 participants	0 participants
Number of Participants With Sickle-Cell Disease-related Symptoms Exacerbation of Sickle Cell (SC) Disease Pain	1 participants	1 participants	0 participants	1 participants	0 participants
Number of Participants With Sickle-Cell Disease-related Symptoms SC Disease Related Pain	0 participants	3 participants	0 participants	1 participants	0 participants
Number of Participants With Sickle-Cell Disease-related Symptoms SC Pain	3 participants	3 participants	1 participants	1 participants	0 participants
Number of Participants With Sickle-Cell Disease-related Symptoms Intermittent SC Pain	1 participants	0 participants	0 participants	0 participants	0 participants
Number of Participants With Sickle-Cell Disease-related Symptoms SC Crisis	1 participants	0 participants	0 participants	0 participants	0 participants
Number of Participants With Sickle-Cell Disease-related Symptoms Vaso-Occlusive Crisis caused by Chest Infection	1 participants	0 participants	0 participants	0 participants	0 participants

PRIMARY outcome

Timeframe: Throughout the study period (approximately 9 weeks)

Population: safety analysis dataset

Vital signs, 12-lead ECGs, clinical laboratory assessments, and physical and neurological examinations that were deemed clinically significant by the investigator in agreement with the sponsor study director.

Outcome measures

Measure	Treatment With Study Product n=23 Participants Participants randomized 3:1 (Aes-103 to placebo) to receive 4 times daily dosing of 1,000 mg of Aes-103 for 28 days	Treatment With Placebo n=11 Participants Participants randomized 3:1 (Aes-103 to placebo) to receive 4 times daily dosing of 1,000 mg of placebo for 28 days	All Treated Participants n=3 Participants All participants randomized 3:1 (Aes-103 to placebo) and received 4 times daily dosing of 1,000 mg AEs-103 or 1,000 mg of placebo for 28 days	Post-treatment With Study Product Observation Period n=12 Participants Participants underwent a post-treatment observation period of 21 days during which no study product (Aes-103) was received	Post-treatment With Placebo Observation Period Participants underwent a post-treatment observation period of 21 days during which no placebo was received
Number of Clinically Significant Observations of Vital Signs, 12-lead ECGs, Clinical Laboratory Assessments, and Physical and Neurological Examinations Electrocardiogram T Wave Inversion	0 clinically significant observations	1 clinically significant observations	0 clinically significant observations	0 clinically significant observations	—
Number of Clinically Significant Observations of Vital Signs, 12-lead ECGs, Clinical Laboratory Assessments, and Physical and Neurological Examinations Transaminases Increased	0 clinically significant observations	0 clinically significant observations	1 clinically significant observations	0 clinically significant observations	—

PRIMARY outcome

Timeframe: PK blood samples were to be taken within 10 minutes before dosing and 0.5, 1, 2, 4, and 6 hours after the first dose of study product on Days 1 and 7 and at the same time points on Day 28 (or early termination)

Population: PK data were not determined as the assay collection method was found to be faulty rendering all samples unevaluable.

Pharmacokinetic endpoints in the study protocol were as follows:- - Plasma Area under curve (AUC), Maximum plasma concentration (Cmax), time at which Cmax observed (Tmax), and terminal half-life (T1/2) of Aes-103 and its metabolite, 5-hydroxymethyl-2-furoic acid (HMFA) - red blood cell (RBC) hemolysate Area under curve between 0 and 8 hours (AUC [0-8h]), Cmax, Tmax, and T1/2 of Aes-103 - Percentage of hemoglobin bound to Aes-103

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Prior to, during and after the end of dosing in the double-blind treatment period, i.e., at baseline, Day 4, Day 7, Day 14 and Day 28

A measure of the amount of oxygen in the blood. Oxygen saturation was determined by pulse oximetry. A pulse oximeter was placed over a nail polish-free finger nail to determine peripheral oxygen saturation (SpO2). Baseline was defined as the most recent value obtained prior to the start of dosing on Day 1 of the double-blind treatment period. A mean change from baseline >0 indicates an increase in oxygen saturation, a mean change <0 indicates a decrease in oxygen saturation. Category title includes number of participants with available data (n) for participants treated with study product, followed by participants treated with placebo.

Outcome measures

Measure	Treatment With Study Product n=11 Participants Participants randomized 3:1 (Aes-103 to placebo) to receive 4 times daily dosing of 1,000 mg of Aes-103 for 28 days	Treatment With Placebo n=3 Participants Participants randomized 3:1 (Aes-103 to placebo) to receive 4 times daily dosing of 1,000 mg of placebo for 28 days	All Treated Participants All participants randomized 3:1 (Aes-103 to placebo) and received 4 times daily dosing of 1,000 mg AEs-103 or 1,000 mg of placebo for 28 days	Post-treatment With Study Product Observation Period Participants underwent a post-treatment observation period of 21 days during which no study product (Aes-103) was received	Post-treatment With Placebo Observation Period Participants underwent a post-treatment observation period of 21 days during which no placebo was received
Resting Oxygen Saturation as Measured by Oximetry (SpO2) - Change From Baseline Day 4 (n=9, 3)	0 percent saturation Standard Deviation 2	4 percent saturation Standard Deviation 5	—	—	—
Resting Oxygen Saturation as Measured by Oximetry (SpO2) - Change From Baseline Day 7 (n= 9, 3)	0 percent saturation Standard Deviation 2	-4 percent saturation Standard Deviation 8	—	—	—
Resting Oxygen Saturation as Measured by Oximetry (SpO2) - Change From Baseline Day 14 (n=8, 2)	0 percent saturation Standard Deviation 2	8 percent saturation Standard Deviation 10	—	—	—
Resting Oxygen Saturation as Measured by Oximetry (SpO2) - Change From Baseline Day 28 (n=8, 2)	0 percent saturation Standard Deviation 3	6 percent saturation Standard Deviation 8	—	—	—

SECONDARY outcome

Timeframe: During the double-blind treatment period at baseline, Day 1, Day 4 and Day 7

A measure of the ability of hemoglobin to bind oxygen. The p50 is the oxygen level at which 50% of the hemoglobin contains oxygen. The p20 is the oxygen level at which 20% of the hemoglobin contains oxygen. Baseline is defined as the most recent value obtained prior to start of dosing on Day 1 of the double-blind treatment period. Category title includes number of participants with available data (n) for participants treated with study product, followed by participants treated with placebo.

Outcome measures

Measure	Treatment With Study Product n=11 Participants Participants randomized 3:1 (Aes-103 to placebo) to receive 4 times daily dosing of 1,000 mg of Aes-103 for 28 days	Treatment With Placebo n=3 Participants Participants randomized 3:1 (Aes-103 to placebo) to receive 4 times daily dosing of 1,000 mg of placebo for 28 days	All Treated Participants All participants randomized 3:1 (Aes-103 to placebo) and received 4 times daily dosing of 1,000 mg AEs-103 or 1,000 mg of placebo for 28 days	Post-treatment With Study Product Observation Period Participants underwent a post-treatment observation period of 21 days during which no study product (Aes-103) was received	Post-treatment With Placebo Observation Period Participants underwent a post-treatment observation period of 21 days during which no placebo was received
Oxygen Binding p50/p20 Value - Change From Baseline Day 4 (n=11, 3)	0.0 ratio Standard Deviation 0.1	0.1 ratio Standard Deviation 0.1	—	—	—
Oxygen Binding p50/p20 Value - Change From Baseline Day 1 (n=11, 3)	0.0 ratio Standard Deviation 0.2	0.0 ratio Standard Deviation 0.2	—	—	—
Oxygen Binding p50/p20 Value - Change From Baseline Day 7 (n=10, 3)	0.0 ratio Standard Deviation 0.2	0.0 ratio Standard Deviation 0.1	—	—	—

SECONDARY outcome

Timeframe: At baseline and Day 28 during the double-blind treatment period

Population: Participants who provided baseline data and at least one other data point for this outcome measure.

Erythropoietin (EPO) is a hormone produced by the kidney that promotes the formation of red blood cells by the bone marrow. EPO can be detected and measured in the blood. Baseline defined as the most recent value obtained prior to the start of dosing on Day 1 of the double-blind treatment period. Category title includes number of participants with available data (n) for participants treated with study product, followed by participants treated with placebo.

Outcome measures

Measure	Treatment With Study Product n=11 Participants Participants randomized 3:1 (Aes-103 to placebo) to receive 4 times daily dosing of 1,000 mg of Aes-103 for 28 days	Treatment With Placebo n=3 Participants Participants randomized 3:1 (Aes-103 to placebo) to receive 4 times daily dosing of 1,000 mg of placebo for 28 days	All Treated Participants All participants randomized 3:1 (Aes-103 to placebo) and received 4 times daily dosing of 1,000 mg AEs-103 or 1,000 mg of placebo for 28 days	Post-treatment With Study Product Observation Period Participants underwent a post-treatment observation period of 21 days during which no study product (Aes-103) was received	Post-treatment With Placebo Observation Period Participants underwent a post-treatment observation period of 21 days during which no placebo was received
Plasma Erythropoietin (EPO) Levels - Change From Baseline	-5.9 U/L Standard Deviation 50.3	-15.1 U/L Standard Deviation 20.4	—	—	—

SECONDARY outcome

Timeframe: Prior to, during and after the end of dosing in the double-blind treatment period, i.e., at baseline, Day 1, Day 7, Day 14 and Day 28

Baseline defined as the most recent value obtained prior to the start of dosing on Day 1 of the double-blind treatment period. Category title includes number of participants with available data (n) for participants treated with study product, followed by participants treated with placebo.

Outcome measures

Measure	Treatment With Study Product n=11 Participants Participants randomized 3:1 (Aes-103 to placebo) to receive 4 times daily dosing of 1,000 mg of Aes-103 for 28 days	Treatment With Placebo n=3 Participants Participants randomized 3:1 (Aes-103 to placebo) to receive 4 times daily dosing of 1,000 mg of placebo for 28 days	All Treated Participants All participants randomized 3:1 (Aes-103 to placebo) and received 4 times daily dosing of 1,000 mg AEs-103 or 1,000 mg of placebo for 28 days	Post-treatment With Study Product Observation Period Participants underwent a post-treatment observation period of 21 days during which no study product (Aes-103) was received	Post-treatment With Placebo Observation Period Participants underwent a post-treatment observation period of 21 days during which no placebo was received
Hematocrit Levels - Change From Baseline Day 14 (n=8, 2)	0.003 L/L Standard Deviation 0.013	-0.006 L/L Standard Deviation 0.015	—	—	—
Hematocrit Levels - Change From Baseline Day 28 (n=8, 2)	0.011 L/L Standard Deviation 0.012	0.006 L/L Standard Deviation 0.007	—	—	—
Hematocrit Levels - Change From Baseline Day 1 (n=11, 3)	0.006 L/L Standard Deviation 0.011	-0.002 L/L Standard Deviation 0.007	—	—	—
Hematocrit Levels - Change From Baseline Day 7 (n=9, 3)	0.007 L/L Standard Deviation 0.013	0.020 L/L Standard Deviation 0.010	—	—	—

SECONDARY outcome

Timeframe: Prior to, during and after the end of dosing in the double-blind treatment period, i.e., at baseline, Day 1, Day 7, Day 14 and Day 28

LDH levels were measured as a biomarker for intravascular hemolysis. The results are based on the LDH Total measurement. Baseline defined as the most recent value obtained prior to the start of dosing on Day 1 of the double-blind treatment period. Category title includes number of participants with available data (n) for participants treated with study product, followed by participants treated with placebo.

Outcome measures

Measure	Treatment With Study Product n=11 Participants Participants randomized 3:1 (Aes-103 to placebo) to receive 4 times daily dosing of 1,000 mg of Aes-103 for 28 days	Treatment With Placebo n=3 Participants Participants randomized 3:1 (Aes-103 to placebo) to receive 4 times daily dosing of 1,000 mg of placebo for 28 days	All Treated Participants All participants randomized 3:1 (Aes-103 to placebo) and received 4 times daily dosing of 1,000 mg AEs-103 or 1,000 mg of placebo for 28 days	Post-treatment With Study Product Observation Period Participants underwent a post-treatment observation period of 21 days during which no study product (Aes-103) was received	Post-treatment With Placebo Observation Period Participants underwent a post-treatment observation period of 21 days during which no placebo was received
Lactate Dehydrogenase (LDH) Levels - Change From Baseline Day 1 (n=11, 3)	60 U/L Standard Deviation 107	0 U/L Standard Deviation 197	—	—	—
Lactate Dehydrogenase (LDH) Levels - Change From Baseline Day 7 (n=9, 3)	71 U/L Standard Deviation 101	-6 U/L Standard Deviation 167	—	—	—
Lactate Dehydrogenase (LDH) Levels - Change From Baseline Day 14 (n=8, 2)	4 U/L Standard Deviation 100	689 U/L Standard Deviation 1142	—	—	—
Lactate Dehydrogenase (LDH) Levels - Change From Baseline Day 28 (n=8, 2)	29 U/L Standard Deviation 110	-69 U/L Standard Deviation 91	—	—	—

SECONDARY outcome

Timeframe: Prior to, during and after the end of dosing in the double-blind treatment period, i.e., at baseline, Day 1, Day 4, Day 7, Day 14, Day 21 and Day 28

A clinical laboratory endpoint that reflects the amount of red blood cells present in the blood. Baseline defined as the most recent value obtained prior to the start of dosing on Day 1 of the double-blind treatment period. Category title includes number of participants with available data (n) for participants treated with study product, followed by participants treated with placebo.

Outcome measures

Measure	Treatment With Study Product n=11 Participants Participants randomized 3:1 (Aes-103 to placebo) to receive 4 times daily dosing of 1,000 mg of Aes-103 for 28 days	Treatment With Placebo n=3 Participants Participants randomized 3:1 (Aes-103 to placebo) to receive 4 times daily dosing of 1,000 mg of placebo for 28 days	All Treated Participants All participants randomized 3:1 (Aes-103 to placebo) and received 4 times daily dosing of 1,000 mg AEs-103 or 1,000 mg of placebo for 28 days	Post-treatment With Study Product Observation Period Participants underwent a post-treatment observation period of 21 days during which no study product (Aes-103) was received	Post-treatment With Placebo Observation Period Participants underwent a post-treatment observation period of 21 days during which no placebo was received
Hemoglobin Levels - Change From Baseline Day 4 (n=10, 3)	1 g/L Standard Deviation 7	3 g/L Standard Deviation 3	—	—	—
Hemoglobin Levels - Change From Baseline Day 7 (n=10, 3)	-1 g/L Standard Deviation 5	3 g/L Standard Deviation 2	—	—	—
Hemoglobin Levels - Change From Baseline Day 14 (n=8, 2)	-2 g/L Standard Deviation 5	-6 g/L Standard Deviation 1	—	—	—
Hemoglobin Levels - Change From Baseline Day 21 (n=2, 0)	1 g/L Standard Deviation 4	NA g/L Standard Deviation NA Data not collected.	—	—	—
Hemoglobin Levels - Change From Baseline Day 28 (n=10, 2)	0 g/L Standard Deviation 4	-2 g/L Standard Deviation 5	—	—	—
Hemoglobin Levels - Change From Baseline Day 1 (n=11, 3)	0 g/L Standard Deviation 5	-3 g/L Standard Deviation 7	—	—	—

SECONDARY outcome

Timeframe: At baseline, Day 1 and Day 7 during the double-blind treatment period

Population: Participants who provided baseline data and at least one other data point for this outcome measure. Summary tables for placebo group not done as data not collected. Study terminated early.

Category title includes number of participants with available data (n) for participants treated with study product.

Outcome measures

Measure	Treatment With Study Product n=2 Participants Participants randomized 3:1 (Aes-103 to placebo) to receive 4 times daily dosing of 1,000 mg of Aes-103 for 28 days	Treatment With Placebo Participants randomized 3:1 (Aes-103 to placebo) to receive 4 times daily dosing of 1,000 mg of placebo for 28 days	All Treated Participants All participants randomized 3:1 (Aes-103 to placebo) and received 4 times daily dosing of 1,000 mg AEs-103 or 1,000 mg of placebo for 28 days	Post-treatment With Study Product Observation Period Participants underwent a post-treatment observation period of 21 days during which no study product (Aes-103) was received	Post-treatment With Placebo Observation Period Participants underwent a post-treatment observation period of 21 days during which no placebo was received
Reticulocyte Percent- Change From Baseline Day 1 (n=2)	-0.46 percent Standard Deviation 0.18	—	—	—	—
Reticulocyte Percent- Change From Baseline Day 7 (n=1)	NA percent Standard Deviation NA When number of participants is less than 2, summary statistics are not computed.	—	—	—	—

SECONDARY outcome

Timeframe: Prior to, during and after the end of dosing in the double-blind treatment period, i.e., at baseline, Day 1, Day 7, Day 14, Day 21 and Day 28

Category title includes number of participants with available data (n) for participants treated with study product, followed by participants treated with placebo.

Outcome measures

Measure	Treatment With Study Product n=11 Participants Participants randomized 3:1 (Aes-103 to placebo) to receive 4 times daily dosing of 1,000 mg of Aes-103 for 28 days	Treatment With Placebo n=3 Participants Participants randomized 3:1 (Aes-103 to placebo) to receive 4 times daily dosing of 1,000 mg of placebo for 28 days	All Treated Participants All participants randomized 3:1 (Aes-103 to placebo) and received 4 times daily dosing of 1,000 mg AEs-103 or 1,000 mg of placebo for 28 days	Post-treatment With Study Product Observation Period Participants underwent a post-treatment observation period of 21 days during which no study product (Aes-103) was received	Post-treatment With Placebo Observation Period Participants underwent a post-treatment observation period of 21 days during which no placebo was received
Direct Bilirubin - Change From Baseline Day 1 (n=11, 3)	0 mircomoles/L Standard Deviation 0	0 mircomoles/L Standard Deviation 0	—	—	—
Direct Bilirubin - Change From Baseline Day 4 (n=10, 3)	0 mircomoles/L Standard Deviation 0	0 mircomoles/L Standard Deviation 0	—	—	—
Direct Bilirubin - Change From Baseline Day 7 (n=10, 3)	0 mircomoles/L Standard Deviation 0	0 mircomoles/L Standard Deviation 0	—	—	—
Direct Bilirubin - Change From Baseline Day 14 (n= 8, 2)	0 mircomoles/L Standard Deviation 0	0 mircomoles/L Standard Deviation 0	—	—	—
Direct Bilirubin - Change From Baseline Day 21 (n=2, 0)	0 mircomoles/L Standard Deviation 0	NA mircomoles/L Standard Deviation NA Data not collected.	—	—	—
Direct Bilirubin - Change From Baseline Day 28 (n=10, 2)	0 mircomoles/L Standard Deviation 0	0 mircomoles/L Standard Deviation 0	—	—	—

SECONDARY outcome

Timeframe: Prior to, during and after the end of dosing in the double-blind treatment period, i.e., at baseline, Day 1, Day 7, Day 14 and Day 28

Population: Summary tables for this outcome measure were not done as baseline data missing. Study terminated early.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: At baseline, Day 1 and Day 7 during the double-blind treatment period

Population: Participants who provided baseline data and at least one other data point for this outcome measure. Summary tables for placebo group not done as data not collected. Study terminated early.

Category title includes number of participants with available data (n) for participants treated with study product.

Outcome measures

Measure	Treatment With Study Product n=2 Participants Participants randomized 3:1 (Aes-103 to placebo) to receive 4 times daily dosing of 1,000 mg of Aes-103 for 28 days	Treatment With Placebo Participants randomized 3:1 (Aes-103 to placebo) to receive 4 times daily dosing of 1,000 mg of placebo for 28 days	All Treated Participants All participants randomized 3:1 (Aes-103 to placebo) and received 4 times daily dosing of 1,000 mg AEs-103 or 1,000 mg of placebo for 28 days	Post-treatment With Study Product Observation Period Participants underwent a post-treatment observation period of 21 days during which no study product (Aes-103) was received	Post-treatment With Placebo Observation Period Participants underwent a post-treatment observation period of 21 days during which no placebo was received
C Reactive Protein Levels - Change From Baseline Day 7 (n=1)	NA mg/L Standard Deviation NA When number of participants is less than 2, summary statistics are not computed.	—	—	—	—
C Reactive Protein Levels - Change From Baseline Day 1 (n=2)	-1.2 mg/L Standard Deviation 3.0	—	—	—	—

SECONDARY outcome

Timeframe: At baseline, Day 1 and Day 7 during the double-blind treatment period

Population: Participants who provided baseline data and at least one other data point for this outcome measure. Summary tables for placebo group not done as data not collected. Study terminated early.

Outcome measures

Measure	Treatment With Study Product n=2 Participants Participants randomized 3:1 (Aes-103 to placebo) to receive 4 times daily dosing of 1,000 mg of Aes-103 for 28 days	Treatment With Placebo Participants randomized 3:1 (Aes-103 to placebo) to receive 4 times daily dosing of 1,000 mg of placebo for 28 days	All Treated Participants All participants randomized 3:1 (Aes-103 to placebo) and received 4 times daily dosing of 1,000 mg AEs-103 or 1,000 mg of placebo for 28 days	Post-treatment With Study Product Observation Period Participants underwent a post-treatment observation period of 21 days during which no study product (Aes-103) was received	Post-treatment With Placebo Observation Period Participants underwent a post-treatment observation period of 21 days during which no placebo was received
Serum Ferritin Levels - Change From Baseline Day 7	NA mircograms/L Standard Deviation NA When number of participants is less than 2, summary statistics are not computed.	—	—	—	—
Serum Ferritin Levels - Change From Baseline Day 1	-4.9 mircograms/L Standard Deviation 0.1	—	—	—	—

SECONDARY outcome

Timeframe: At baseline, Day 1, Day 7, Day 14 and Day 28 during the double-blind treatment period

Population: Participants who provided baseline data and at least one other data point for this outcome measure. Summary tables for placebo group not done as data not collected. Study terminated early.

Category title includes number of participants with available data (n) for participants treated with study product.

Outcome measures

Measure	Treatment With Study Product n=9 Participants Participants randomized 3:1 (Aes-103 to placebo) to receive 4 times daily dosing of 1,000 mg of Aes-103 for 28 days	Treatment With Placebo Participants randomized 3:1 (Aes-103 to placebo) to receive 4 times daily dosing of 1,000 mg of placebo for 28 days	All Treated Participants All participants randomized 3:1 (Aes-103 to placebo) and received 4 times daily dosing of 1,000 mg AEs-103 or 1,000 mg of placebo for 28 days	Post-treatment With Study Product Observation Period Participants underwent a post-treatment observation period of 21 days during which no study product (Aes-103) was received	Post-treatment With Placebo Observation Period Participants underwent a post-treatment observation period of 21 days during which no placebo was received
N-terminal Pro B-type Natriuretic Peptide (NT-proBNP) Levels- Change From Baseline Day 1 (n=7)	6 pmol/L Standard Deviation 15	—	—	—	—
N-terminal Pro B-type Natriuretic Peptide (NT-proBNP) Levels- Change From Baseline Day 7 (n=6)	6 pmol/L Standard Deviation 97	—	—	—	—
N-terminal Pro B-type Natriuretic Peptide (NT-proBNP) Levels- Change From Baseline Day 14 (n=6)	32 pmol/L Standard Deviation 25	—	—	—	—
N-terminal Pro B-type Natriuretic Peptide (NT-proBNP) Levels- Change From Baseline Day 28 (n=7)	1 pmol/L Standard Deviation 55	—	—	—	—

SECONDARY outcome

Timeframe: Prior to, during and after the end of dosing in the double-blind treatment period, i.e., at baseline, Day 1, Day 4, Day 7, Day 14, Day 21 and Day 28

A negative change in body weight denotes a weight decrease, a positive change in body weight denotes a weight increase. Category title includes number of participants with available data (n) for participants treated with study product, followed by participants treated with placebo.

Outcome measures

Measure	Treatment With Study Product n=11 Participants Participants randomized 3:1 (Aes-103 to placebo) to receive 4 times daily dosing of 1,000 mg of Aes-103 for 28 days	Treatment With Placebo n=3 Participants Participants randomized 3:1 (Aes-103 to placebo) to receive 4 times daily dosing of 1,000 mg of placebo for 28 days	All Treated Participants All participants randomized 3:1 (Aes-103 to placebo) and received 4 times daily dosing of 1,000 mg AEs-103 or 1,000 mg of placebo for 28 days	Post-treatment With Study Product Observation Period Participants underwent a post-treatment observation period of 21 days during which no study product (Aes-103) was received	Post-treatment With Placebo Observation Period Participants underwent a post-treatment observation period of 21 days during which no placebo was received
Body Weight - Change From Baseline Day 1 (n=11, 3)	-0.2 kg Standard Deviation 0.7	-0.6 kg Standard Deviation 0.4	—	—	—
Body Weight - Change From Baseline Day 7 (n=10, 3)	-0.5 kg Standard Deviation 1.6	-0.7 kg Standard Deviation 1.3	—	—	—
Body Weight - Change From Baseline Day 14 (n=8, 2)	1.1 kg Standard Deviation 0.8	0.8 kg Standard Deviation 0.7	—	—	—
Body Weight - Change From Baseline Day 21 (n=6, 2)	0.1 kg Standard Deviation 1.4	0.5 kg Standard Deviation 0.1	—	—	—
Body Weight - Change From Baseline Day 28 (n=10, 2)	0.6 kg Standard Deviation 0.9	0.4 kg Standard Deviation 0.4	—	—	—
Body Weight - Change From Baseline Day 4 (n=10, 3)	-0.3 kg Standard Deviation 1.6	-0.4 kg Standard Deviation 0.8	—	—	—

SECONDARY outcome

Timeframe: Prior to, during and after the end of dosing in the double-blind treatment period, i.e., at baseline, Day 4, Day 7, Day 14 and Day 28

Functional exercise capacity was evaluated by using the 6-minute walk test (6MWT) which measures the distance that a subject can quickly walk on a flat, hard surface in a period of 6 minutes. Guidelines developed by the American Thoracic Society were used for conducting the test and interpreting the results. Baseline defined as the most recent value obtained prior to the start of dosing on Day 1. Category title includes number of participants with available data (n) for participants treated with study product, followed by participants treated with placebo.

Outcome measures

Measure	Treatment With Study Product n=11 Participants Participants randomized 3:1 (Aes-103 to placebo) to receive 4 times daily dosing of 1,000 mg of Aes-103 for 28 days	Treatment With Placebo n=3 Participants Participants randomized 3:1 (Aes-103 to placebo) to receive 4 times daily dosing of 1,000 mg of placebo for 28 days	All Treated Participants All participants randomized 3:1 (Aes-103 to placebo) and received 4 times daily dosing of 1,000 mg AEs-103 or 1,000 mg of placebo for 28 days	Post-treatment With Study Product Observation Period Participants underwent a post-treatment observation period of 21 days during which no study product (Aes-103) was received	Post-treatment With Placebo Observation Period Participants underwent a post-treatment observation period of 21 days during which no placebo was received
Exercise Tolerance: 6-Minute Walk Distance During the Double-blind Treatment Period - Change From Baseline Day 4 (n=9, 3)	-8.5 meters Standard Deviation 38.2	20.6 meters Standard Deviation 8.0	—	—	—
Exercise Tolerance: 6-Minute Walk Distance During the Double-blind Treatment Period - Change From Baseline Day 7 (n=9, 3)	36.9 meters Standard Deviation 44.6	28.3 meters Standard Deviation 24.3	—	—	—
Exercise Tolerance: 6-Minute Walk Distance During the Double-blind Treatment Period - Change From Baseline Day 14 (n=8, 2)	-0.1 meters Standard Deviation 31.5	4.1 meters Standard Deviation 6.1	—	—	—
Exercise Tolerance: 6-Minute Walk Distance During the Double-blind Treatment Period - Change From Baseline Day 28 (n=8, 2)	-14.9 meters Standard Deviation 41.2	-8.2 meters Standard Deviation 8.2	—	—	—

SECONDARY outcome

Timeframe: Prior to dosing at baseline and on Day 49 of the post-treatment observation period

Population: Participants who provided baseline data and at least one other data point for this outcome measure.

Functional exercise capacity was evaluated by using the 6-minute walk test (6MWT) which measures the distance that a subject can quickly walk on a flat, hard surface in a period of 6 minutes. Guidelines developed by the American Thoracic Society were used for conducting the test and interpreting the results. Baseline defined as the most recent value obtained prior to the start of dosing on Day 1.

Outcome measures

Measure	Treatment With Study Product n=8 Participants Participants randomized 3:1 (Aes-103 to placebo) to receive 4 times daily dosing of 1,000 mg of Aes-103 for 28 days	Treatment With Placebo n=2 Participants Participants randomized 3:1 (Aes-103 to placebo) to receive 4 times daily dosing of 1,000 mg of placebo for 28 days	All Treated Participants All participants randomized 3:1 (Aes-103 to placebo) and received 4 times daily dosing of 1,000 mg AEs-103 or 1,000 mg of placebo for 28 days	Post-treatment With Study Product Observation Period Participants underwent a post-treatment observation period of 21 days during which no study product (Aes-103) was received	Post-treatment With Placebo Observation Period Participants underwent a post-treatment observation period of 21 days during which no placebo was received
Exercise Tolerance: 6-Minute Walk Distance on Day 49 of the Post-treatment Observation Period - Change From Baseline	-20.6 meters Standard Deviation 41.3	-1.1 meters Standard Deviation 3.5	—	—	—

SECONDARY outcome

Timeframe: On last day of double-blind treatment period (Day 28) and on Day 49 of the post-treatment observation period

Population: Participants who provided baseline data and at least one other data point for this outcome measure.

Functional exercise capacity was evaluated by using the 6-minute walk test (6MWT) which measures the distance that a subject can quickly walk on a flat, hard surface in a period of 6 minutes. Guidelines developed by the American Thoracic Society were used for conducting the test and interpreting the results.

Outcome measures

Measure	Treatment With Study Product n=8 Participants Participants randomized 3:1 (Aes-103 to placebo) to receive 4 times daily dosing of 1,000 mg of Aes-103 for 28 days	Treatment With Placebo n=2 Participants Participants randomized 3:1 (Aes-103 to placebo) to receive 4 times daily dosing of 1,000 mg of placebo for 28 days	All Treated Participants All participants randomized 3:1 (Aes-103 to placebo) and received 4 times daily dosing of 1,000 mg AEs-103 or 1,000 mg of placebo for 28 days	Post-treatment With Study Product Observation Period Participants underwent a post-treatment observation period of 21 days during which no study product (Aes-103) was received	Post-treatment With Placebo Observation Period Participants underwent a post-treatment observation period of 21 days during which no placebo was received
Exercise Tolerance: 6-Minute Walk Distance on Day 49 of the Post-treatment Observation Period - Change From Last Day of Double-blind Treatment Period (Day 28)	-5.6 meters Standard Deviation 63.6	7.2 meters Standard Deviation 4.7	—	—	—

SECONDARY outcome

Timeframe: On last day of double-blind treatment period (Day 28)

Population: Following an external review and report of CPET capabilities of the external service provider, all CPET testing was suspended and the decision made to not collect or analyze CPET data.

CPET was optional, based on capacity of participant to complete the test.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: At baseline and once weekly on Days 7, 14, 21, and 28 during the double-blind treatment period

Participants assessed the change in activity limitations, symptoms, emotions, and overall quality of life by using the 1- to 7-point PGIC scale. The question and scale was as follows: Since beginning treatment at this clinic, how would you describe the change in your sickle cell condition? Please circle the number that matches your overall judgment. -3 - much worse -2 - moderately worse -1 - minimally worse 0 - no change +1 - minimally improved +2 - moderately improved +3 - much improved. Baseline defined as the most recent value obtained prior to the start of dosing on Day 1 of the double-blind treatment period. No values available for placebo group for Day 28. Category title includes number of participants with available data (n) for participants treated with study product, followed by participants treated with placebo.

Outcome measures

Measure	Treatment With Study Product n=11 Participants Participants randomized 3:1 (Aes-103 to placebo) to receive 4 times daily dosing of 1,000 mg of Aes-103 for 28 days	Treatment With Placebo n=3 Participants Participants randomized 3:1 (Aes-103 to placebo) to receive 4 times daily dosing of 1,000 mg of placebo for 28 days	All Treated Participants All participants randomized 3:1 (Aes-103 to placebo) and received 4 times daily dosing of 1,000 mg AEs-103 or 1,000 mg of placebo for 28 days	Post-treatment With Study Product Observation Period Participants underwent a post-treatment observation period of 21 days during which no study product (Aes-103) was received	Post-treatment With Placebo Observation Period Participants underwent a post-treatment observation period of 21 days during which no placebo was received
Patients´ Global Impression of Change (PGIC) During the Double-blind Treatment Period - Change From Baseline Day 28 (n=9, 1)	0 score on a scale Standard Deviation 1	NA score on a scale Standard Deviation NA When number of participants is less than 2, summary statistics are not computed.	—	—	—
Patients´ Global Impression of Change (PGIC) During the Double-blind Treatment Period - Change From Baseline Day 7 (n=10, 3)	0 score on a scale Standard Deviation 1	0 score on a scale Standard Deviation 0	—	—	—
Patients´ Global Impression of Change (PGIC) During the Double-blind Treatment Period - Change From Baseline Day 14 (n=9, 2)	0 score on a scale Standard Deviation 0	0 score on a scale Standard Deviation 0	—	—	—
Patients´ Global Impression of Change (PGIC) During the Double-blind Treatment Period - Change From Baseline Day 21 (n=8, 2)	0 score on a scale Standard Deviation 1	0 score on a scale Standard Deviation 0	—	—	—

SECONDARY outcome

Timeframe: At baseline and once weekly on Days 35, 42, and 49 during the post-treatment observation period

Participants assessed the change in activity limitations, symptoms, emotions, and overall quality of life by using the 1- to 7-point PGIC scale. The question and scale was as follows: Since beginning treatment at this clinic, how would you describe the change in your sickle cell condition? Please circle the number that matches your overall judgment. -3 - much worse -2 - moderately worse -1 - minimally worse 0 - no change +1 - minimally improved +2 - moderately improved +3 - much improved. Baseline defined as the most recent value obtained prior to the start of dosing on Day 1 of the double-blind treatment period. Category title includes number of participants with available data (n) for participants treated with study product, followed by participants treated with placebo.

Outcome measures

Measure	Treatment With Study Product n=10 Participants Participants randomized 3:1 (Aes-103 to placebo) to receive 4 times daily dosing of 1,000 mg of Aes-103 for 28 days	Treatment With Placebo n=2 Participants Participants randomized 3:1 (Aes-103 to placebo) to receive 4 times daily dosing of 1,000 mg of placebo for 28 days	All Treated Participants All participants randomized 3:1 (Aes-103 to placebo) and received 4 times daily dosing of 1,000 mg AEs-103 or 1,000 mg of placebo for 28 days	Post-treatment With Study Product Observation Period Participants underwent a post-treatment observation period of 21 days during which no study product (Aes-103) was received	Post-treatment With Placebo Observation Period Participants underwent a post-treatment observation period of 21 days during which no placebo was received
Patients´ Global Impression of Change (PGIC) During the Post-treatment Observation Period - Change From Baseline Day 49 (n=8, 2)	0 score on a scale Standard Deviation 1	0 score on a scale Standard Deviation 0	—	—	—
Patients´ Global Impression of Change (PGIC) During the Post-treatment Observation Period - Change From Baseline Day 35 (n=8, 2)	0 score on a scale Standard Deviation 1	0 score on a scale Standard Deviation 0	—	—	—
Patients´ Global Impression of Change (PGIC) During the Post-treatment Observation Period - Change From Baseline Day 42 (n=10, 2)	0 score on a scale Standard Deviation 1	0 score on a scale Standard Deviation 0	—	—	—

SECONDARY outcome

Timeframe: At baseline and once weekly on Days 35, 42, and 49 during the post-treatment observation period

Participants assessed the change in activity limitations, symptoms, emotions, and overall quality of life by using the 1- to 7-point PGIC scale. The question and scale was as follows: Since beginning treatment at this clinic, how would you describe the change in your sickle cell condition? Please circle the number that matches your overall judgment. -3 - much worse -2 - moderately worse -1 - minimally worse 0 - no change +1 - minimally improved +2 - moderately improved +3 - much improved. Baseline was defined as the most recent value obtained on the last day of the double-blind treatment period. Categories contain Category title includes number of participants with available data (n) for participants treated with study product, followed by participants treated with placebo.

Outcome measures

Measure	Treatment With Study Product n=10 Participants Participants randomized 3:1 (Aes-103 to placebo) to receive 4 times daily dosing of 1,000 mg of Aes-103 for 28 days	Treatment With Placebo n=2 Participants Participants randomized 3:1 (Aes-103 to placebo) to receive 4 times daily dosing of 1,000 mg of placebo for 28 days	All Treated Participants All participants randomized 3:1 (Aes-103 to placebo) and received 4 times daily dosing of 1,000 mg AEs-103 or 1,000 mg of placebo for 28 days	Post-treatment With Study Product Observation Period Participants underwent a post-treatment observation period of 21 days during which no study product (Aes-103) was received	Post-treatment With Placebo Observation Period Participants underwent a post-treatment observation period of 21 days during which no placebo was received
Patients´ Global Impression of Change (PGIC) During the Post-treatment Observation Period - Change From Last Day of Double-blind Treatment Period Day 35 (n=8, 2)	0 score on a scale Standard Deviation 0	0 score on a scale Standard Deviation 0	—	—	—
Patients´ Global Impression of Change (PGIC) During the Post-treatment Observation Period - Change From Last Day of Double-blind Treatment Period Day 42 (n=10, 2)	0 score on a scale Standard Deviation 0	0 score on a scale Standard Deviation 0	—	—	—
Patients´ Global Impression of Change (PGIC) During the Post-treatment Observation Period - Change From Last Day of Double-blind Treatment Period Day 49 (n=8, 2)	0 score on a scale Standard Deviation 0	0 score on a scale Standard Deviation 0	—	—	—

SECONDARY outcome

Timeframe: Participants assessed and recorded their pain level daily. Weekly averages were calculated for the Day 7, Day 14, Day 21, and Day 28 assessments

Participants assessed their pain levels by using the 0-10 Numeric Rating Scale: 0 = No pain 1-3 = Mild pain (nagging, annoying, interfering little with activities of daily living [ADLs]) 4-6 = Moderate pain (interferes significantly with ADLs) 7-10 = Severe pain (disabling; unable to perform ADLs A negative mean change denotes a pain decrease. A positive mean change denotes an increase in pain. Baseline was defined as the average of all measures taken from screening through the period prior to start of dosing on Day 1. Category title includes number of participants with available data (n) for participants treated with study product, followed by participants treated with placebo.

Outcome measures

Measure	Treatment With Study Product n=11 Participants Participants randomized 3:1 (Aes-103 to placebo) to receive 4 times daily dosing of 1,000 mg of Aes-103 for 28 days	Treatment With Placebo n=3 Participants Participants randomized 3:1 (Aes-103 to placebo) to receive 4 times daily dosing of 1,000 mg of placebo for 28 days	All Treated Participants All participants randomized 3:1 (Aes-103 to placebo) and received 4 times daily dosing of 1,000 mg AEs-103 or 1,000 mg of placebo for 28 days	Post-treatment With Study Product Observation Period Participants underwent a post-treatment observation period of 21 days during which no study product (Aes-103) was received	Post-treatment With Placebo Observation Period Participants underwent a post-treatment observation period of 21 days during which no placebo was received
Numerical Pain Rating Scale (NPRS): Worst Pain (Weekly Average) in the Double-blind Treatment Period - Change From Baseline Day 7 (n=11, 3)	1.682 score on a scale Standard Deviation 3.482	4.533 score on a scale Standard Deviation 4.536	—	—	—
Numerical Pain Rating Scale (NPRS): Worst Pain (Weekly Average) in the Double-blind Treatment Period - Change From Baseline Day 14 (n=10, 2)	-0.850 score on a scale Standard Deviation 1.255	-0.650 score on a scale Standard Deviation 0.071	—	—	—
Numerical Pain Rating Scale (NPRS): Worst Pain (Weekly Average) in the Double-blind Treatment Period - Change From Baseline Day 21 (n=8, 2)	-0.825 score on a scale Standard Deviation 1.302	-0.650 score on a scale Standard Deviation 0.071	—	—	—
Numerical Pain Rating Scale (NPRS): Worst Pain (Weekly Average) in the Double-blind Treatment Period - Change From Baseline Day 28 (n=9, 2)	0.689 score on a scale Standard Deviation 1.279	-0.650 score on a scale Standard Deviation 0.071	—	—	—

SECONDARY outcome

Timeframe: Participants assessed and recorded their pain level daily. Weekly averages were calculated for the Day 7, Day 14, Day 21, and Day 28 assessments

Participants assessed their pain levels by using the 0-10 Numeric Rating Scale: 0 = No pain 1-3 = Mild pain (nagging, annoying, interfering little with activities of daily living [ADLs]) 4-6 = Moderate pain (interferes significantly with ADLs) 7-10 = Severe pain (disabling; unable to perform ADLs A negative mean change denotes a pain decrease. A positive mean change denotes an increase in pain. Baseline was defined as the average of all measures taken from screening through the period prior to start of dosing on Day 1. Area under the curve (AUC) was computed using change from baseline in weekly average values at Day 7, Day 14, Day 21. and Day 28.

Outcome measures

Measure	Treatment With Study Product n=11 Participants Participants randomized 3:1 (Aes-103 to placebo) to receive 4 times daily dosing of 1,000 mg of Aes-103 for 28 days	Treatment With Placebo n=3 Participants Participants randomized 3:1 (Aes-103 to placebo) to receive 4 times daily dosing of 1,000 mg of placebo for 28 days	All Treated Participants All participants randomized 3:1 (Aes-103 to placebo) and received 4 times daily dosing of 1,000 mg AEs-103 or 1,000 mg of placebo for 28 days	Post-treatment With Study Product Observation Period Participants underwent a post-treatment observation period of 21 days during which no study product (Aes-103) was received	Post-treatment With Placebo Observation Period Participants underwent a post-treatment observation period of 21 days during which no placebo was received
Numerical Pain Rating Scale (NPRS): Worst Pain (Weekly Average) in the Double-blind Treatment Period - AUC	-2.352 NPRS score*week Standard Deviation 2.674	-3.229 NPRS score*week Standard Deviation 2.847	—	—	—

SECONDARY outcome

Timeframe: Participants assessed and recorded their pain level daily. Weekly averages were calculated for the Day 35, Day 42 and Day 49 assessments

Participants assessed their pain levels by using the 0-10 Numeric Rating Scale: 0 = No pain 1-3 = Mild pain (nagging, annoying, interfering little with activities of daily living [ADLs]) 4-6 = Moderate pain (interferes significantly with ADLs) 7-10 = Severe pain (disabling; unable to perform ADLs A negative mean change denotes a pain decrease. A positive mean change denotes an increase in pain. Baseline was defined as the average of all measures taken from screening through the period prior to start of dosing on Day 1. Category title includes number of participants with available data (n) for participants treated with study product, followed by participants treated with placebo.

Outcome measures

Measure	Treatment With Study Product n=10 Participants Participants randomized 3:1 (Aes-103 to placebo) to receive 4 times daily dosing of 1,000 mg of Aes-103 for 28 days	Treatment With Placebo n=2 Participants Participants randomized 3:1 (Aes-103 to placebo) to receive 4 times daily dosing of 1,000 mg of placebo for 28 days	All Treated Participants All participants randomized 3:1 (Aes-103 to placebo) and received 4 times daily dosing of 1,000 mg AEs-103 or 1,000 mg of placebo for 28 days	Post-treatment With Study Product Observation Period Participants underwent a post-treatment observation period of 21 days during which no study product (Aes-103) was received	Post-treatment With Placebo Observation Period Participants underwent a post-treatment observation period of 21 days during which no placebo was received
Numerical Pain Rating Scale (NPRS): Worst Pain (Weekly Average) in the Post-treatment Observation Period - Change From Baseline Day 42 (n=10, 2)	-2.830 score on a scale Standard Deviation 5.494	-7.750 score on a scale Standard Deviation 1.202	—	—	—
Numerical Pain Rating Scale (NPRS): Worst Pain (Weekly Average) in the Post-treatment Observation Period - Change From Baseline Day 35 (n=8, 2)	-4.675 score on a scale Standard Deviation 3.729	-7.750 score on a scale Standard Deviation 1.202	—	—	—
Numerical Pain Rating Scale (NPRS): Worst Pain (Weekly Average) in the Post-treatment Observation Period - Change From Baseline Day 49 (n=9, 2)	-3.089 score on a scale Standard Deviation 6.049	-8.15 score on a scale Standard Deviation 0.212	—	—	—

SECONDARY outcome

Timeframe: Participants assessed and recorded their pain level daily. Weekly averages were calculated for the Day 35, Day 42 and Day 49 assessments

Participants assessed their pain levels by using the 0-10 Numeric Rating Scale: 0 = No pain 1-3 = Mild pain (nagging, annoying, interfering little with activities of daily living [ADLs]) 4-6 = Moderate pain (interferes significantly with ADLs) 7-10 = Severe pain (disabling; unable to perform ADLs A negative mean change denotes a pain decrease. A positive mean change denotes an increase in pain. Baseline was defined as the average of all measures taken from screening through the period prior to start of dosing on Day 1. Area under the curve (AUC) was computed using change from baseline in weekly average values at Day 7, Day 14, Day 21, Day 28, Day 35, Day 42 and Day 49.

Outcome measures

Measure	Treatment With Study Product n=10 Participants Participants randomized 3:1 (Aes-103 to placebo) to receive 4 times daily dosing of 1,000 mg of Aes-103 for 28 days	Treatment With Placebo n=2 Participants Participants randomized 3:1 (Aes-103 to placebo) to receive 4 times daily dosing of 1,000 mg of placebo for 28 days	All Treated Participants All participants randomized 3:1 (Aes-103 to placebo) and received 4 times daily dosing of 1,000 mg AEs-103 or 1,000 mg of placebo for 28 days	Post-treatment With Study Product Observation Period Participants underwent a post-treatment observation period of 21 days during which no study product (Aes-103) was received	Post-treatment With Placebo Observation Period Participants underwent a post-treatment observation period of 21 days during which no placebo was received
Numerical Pain Rating Scale (NPRS): Worst Pain (Weekly Average) in the Post-treatment Observation Period - AUC	-2.836 NPRS score*week Standard Deviation 3.637	-6.118 NPRS score*week Standard Deviation 0.874	—	—	—

SECONDARY outcome

Timeframe: Participants assessed and recorded their pain level daily. Weekly averages were calculated for the Day 35, Day 42 and Day 49 assessments

Participants assessed their pain levels by using the 0-10 Numeric Rating Scale: 0 = No pain 1-3 = Mild pain (nagging, annoying, interfering little with activities of daily living [ADLs]) 4-6 = Moderate pain (interferes significantly with ADLs) 7-10 = Severe pain (disabling; unable to perform ADLs A negative mean change denotes a pain decrease. A positive mean change denotes an increase in pain. Baseline was defined as the most recent value obtained on the last day of the double-blind dosing period (Day 28). Category title includes number of participants with available data (n) for participants treated with study product, followed by participants treated with placebo.

Outcome measures

Measure	Treatment With Study Product n=10 Participants Participants randomized 3:1 (Aes-103 to placebo) to receive 4 times daily dosing of 1,000 mg of Aes-103 for 28 days	Treatment With Placebo n=2 Participants Participants randomized 3:1 (Aes-103 to placebo) to receive 4 times daily dosing of 1,000 mg of placebo for 28 days	All Treated Participants All participants randomized 3:1 (Aes-103 to placebo) and received 4 times daily dosing of 1,000 mg AEs-103 or 1,000 mg of placebo for 28 days	Post-treatment With Study Product Observation Period Participants underwent a post-treatment observation period of 21 days during which no study product (Aes-103) was received	Post-treatment With Placebo Observation Period Participants underwent a post-treatment observation period of 21 days during which no placebo was received
Numerical Pain Rating Scale (NPRS): Worst Pain (Weekly Average) in the Post-treatment Observation Period - Change From Last Day of Double-blind Treatment Period (Day 28) Day 35 (n=8, 2)	-3.425 score on a scale Standard Deviation 3.302	-7.750 score on a scale Standard Deviation 1.202	—	—	—
Numerical Pain Rating Scale (NPRS): Worst Pain (Weekly Average) in the Post-treatment Observation Period - Change From Last Day of Double-blind Treatment Period (Day 28) Day 42 (n=10, 2)	-1.830 score on a scale Standard Deviation 4.905	-7.750 score on a scale Standard Deviation 1.202	—	—	—
Numerical Pain Rating Scale (NPRS): Worst Pain (Weekly Average) in the Post-treatment Observation Period - Change From Last Day of Double-blind Treatment Period (Day 28) Day 49 (n=9, 2)	-1.978 score on a scale Standard Deviation 5.479	-8.150 score on a scale Standard Deviation 0.212	—	—	—

SECONDARY outcome

Timeframe: Participants assessed and recorded their pain level daily. Weekly averages were calculated for the Day 35, Day 42 and Day 49 assessments

Participants assessed their pain levels by using the 0-10 Numeric Rating Scale: 0 = No pain 1-3 = Mild pain (nagging, annoying, interfering little with activities of daily living [ADLs]) 4-6 = Moderate pain (interferes significantly with ADLs) 7-10 = Severe pain (disabling; unable to perform ADLs A negative mean change denotes a pain decrease. A positive mean change denotes an increase in pain. Baseline was defined as the most recent value obtained on the last day of the double-blind dosing period (Day 28). Area under the curve (AUC) was computed using change from baseline (Day 28) in weekly average values at Day 35, Day 42 and Day 49.

Outcome measures

Measure	Treatment With Study Product n=10 Participants Participants randomized 3:1 (Aes-103 to placebo) to receive 4 times daily dosing of 1,000 mg of Aes-103 for 28 days	Treatment With Placebo n=2 Participants Participants randomized 3:1 (Aes-103 to placebo) to receive 4 times daily dosing of 1,000 mg of placebo for 28 days	All Treated Participants All participants randomized 3:1 (Aes-103 to placebo) and received 4 times daily dosing of 1,000 mg AEs-103 or 1,000 mg of placebo for 28 days	Post-treatment With Study Product Observation Period Participants underwent a post-treatment observation period of 21 days during which no study product (Aes-103) was received	Post-treatment With Placebo Observation Period Participants underwent a post-treatment observation period of 21 days during which no placebo was received
Numerical Pain Rating Scale (NPRS): Worst Pain (Weekly Average) in the Post-treatment Observation Period - Change From Last Day of Double-blind Treatment Period (Day 28) - AUC	-2.836 NPRS score*week Standard Deviation 3.637	-6.118 NPRS score*week Standard Deviation 0.874	—	—	—

SECONDARY outcome

Timeframe: At baseline, Day 7 and Day 28 during the double-blind treatment period

Population: Participants who provided baseline data and at least one other data point for this outcome measure.

Participants rated the severity of their pain by using the BPI short form. Pain was rated on a scale from 0 (no pain) to 10 (pain as bad as you can imagine). A negative mean change denotes a pain decrease. A positive mean change denotes an increase in pain. Baseline was defined as the most recent value obtained prior to the start of the dosing on Day 1 of the double-blind dosing period. Category title includes number of participants with available data (n) for participants treated with study product, followed by participants treated with placebo.

Outcome measures

Measure	Treatment With Study Product n=11 Participants Participants randomized 3:1 (Aes-103 to placebo) to receive 4 times daily dosing of 1,000 mg of Aes-103 for 28 days	Treatment With Placebo n=3 Participants Participants randomized 3:1 (Aes-103 to placebo) to receive 4 times daily dosing of 1,000 mg of placebo for 28 days	All Treated Participants All participants randomized 3:1 (Aes-103 to placebo) and received 4 times daily dosing of 1,000 mg AEs-103 or 1,000 mg of placebo for 28 days	Post-treatment With Study Product Observation Period Participants underwent a post-treatment observation period of 21 days during which no study product (Aes-103) was received	Post-treatment With Placebo Observation Period Participants underwent a post-treatment observation period of 21 days during which no placebo was received
Brief Pain Inventory (BPI): Average Pain Level in Last 24 Hours (Double-blind Treatment Period) - Change From Baseline Day 7 (n=10, 3)	-0.4 score on a scale Standard Deviation 2.3	-3.0 score on a scale Standard Deviation 3.3	—	—	—
Brief Pain Inventory (BPI): Average Pain Level in Last 24 Hours (Double-blind Treatment Period) - Change From Baseline Day 28 (n=8, 2)	-0.6 score on a scale Standard Deviation 1.2	-1.3 score on a scale Standard Deviation 3.2	—	—	—

SECONDARY outcome

Timeframe: At baseline, Day 7 and Day 28 during the double-blind treatment period

Population: Participants who provided baseline data and at least one other data point for this outcome measure.

Participants rated the severity of their pain by using the BPI short form. Pain was rated on a scale from 0 (no pain) to 10 (pain as bad as you can imagine). A negative mean change denotes a pain decrease. A positive mean change denotes an increase in pain. Baseline was defined as the most recent value obtained prior to the start of the dosing on Day 1 of the double-blind dosing period. Category title includes number of participants with available data (n) for participants treated with study product, followed by participants treated with placebo.

Outcome measures

Measure	Treatment With Study Product n=11 Participants Participants randomized 3:1 (Aes-103 to placebo) to receive 4 times daily dosing of 1,000 mg of Aes-103 for 28 days	Treatment With Placebo n=3 Participants Participants randomized 3:1 (Aes-103 to placebo) to receive 4 times daily dosing of 1,000 mg of placebo for 28 days	All Treated Participants All participants randomized 3:1 (Aes-103 to placebo) and received 4 times daily dosing of 1,000 mg AEs-103 or 1,000 mg of placebo for 28 days	Post-treatment With Study Product Observation Period Participants underwent a post-treatment observation period of 21 days during which no study product (Aes-103) was received	Post-treatment With Placebo Observation Period Participants underwent a post-treatment observation period of 21 days during which no placebo was received
Brief Pain Inventory (BPI): Worst Pain Level in Last 24 Hours (Double-blind Treatment Period) - Change From Baseline Day 7 (n=10, 3)	-1 score on a scale Standard Deviation 3	0 score on a scale Standard Deviation 0	—	—	—
Brief Pain Inventory (BPI): Worst Pain Level in Last 24 Hours (Double-blind Treatment Period) - Change From Baseline Day 28 (n=8, 2)	-1 score on a scale Standard Deviation 3	1 score on a scale Standard Deviation 1	—	—	—

SECONDARY outcome

Timeframe: At baseline and Day 49 during the post-treatment observation period

Population: Participants who provided baseline data and at least one other data point for this outcome measure.

Participants rated the severity of their pain by using the BPI short form. Pain was rated on a scale from 0 (no pain) to 10 (pain as bad as you can imagine). A negative mean change denotes a pain decrease. A positive mean change denotes an increase in pain. Baseline was defined as the most recent value obtained prior to the start of the dosing on Day 1 of the double-blind dosing period.

Outcome measures

Measure	Treatment With Study Product n=8 Participants Participants randomized 3:1 (Aes-103 to placebo) to receive 4 times daily dosing of 1,000 mg of Aes-103 for 28 days	Treatment With Placebo n=2 Participants Participants randomized 3:1 (Aes-103 to placebo) to receive 4 times daily dosing of 1,000 mg of placebo for 28 days	All Treated Participants All participants randomized 3:1 (Aes-103 to placebo) and received 4 times daily dosing of 1,000 mg AEs-103 or 1,000 mg of placebo for 28 days	Post-treatment With Study Product Observation Period Participants underwent a post-treatment observation period of 21 days during which no study product (Aes-103) was received	Post-treatment With Placebo Observation Period Participants underwent a post-treatment observation period of 21 days during which no placebo was received
Brief Pain Inventory (BPI): Worst Pain Level in Last 24 Hours (Post-treatment Observation Period) - Change From Baseline	-1 score on a scale Standard Deviation 5	0 score on a scale Standard Deviation 0	—	—	—

SECONDARY outcome

Timeframe: At baseline, Day 7 and Day 28 during the double-blind treatment period

Population: Participants who provided baseline data and at least one other data point for this outcome measure.

Participants rated the degree to which their pain interfered with various daily functions by using the BPI short form. Interference with general activity was rated on a scale from 0 (does not interfere) to 10 (completely interferes). Baseline was defined as the most recent value obtained prior to the start of the dosing on Day 1 of the double-blind dosing period. Category title includes number of participants with available data (n) for participants treated with study product, followed by participants treated with placebo.

Outcome measures

Measure	Treatment With Study Product n=11 Participants Participants randomized 3:1 (Aes-103 to placebo) to receive 4 times daily dosing of 1,000 mg of Aes-103 for 28 days	Treatment With Placebo n=3 Participants Participants randomized 3:1 (Aes-103 to placebo) to receive 4 times daily dosing of 1,000 mg of placebo for 28 days	All Treated Participants All participants randomized 3:1 (Aes-103 to placebo) and received 4 times daily dosing of 1,000 mg AEs-103 or 1,000 mg of placebo for 28 days	Post-treatment With Study Product Observation Period Participants underwent a post-treatment observation period of 21 days during which no study product (Aes-103) was received	Post-treatment With Placebo Observation Period Participants underwent a post-treatment observation period of 21 days during which no placebo was received
Brief Pain Inventory (BPI): Interference of Pain With Aspects of Life (General Activity) During Double-blind Treatment Period - Change From Baseline Day 28 (n=8, 2)	1 score on a scale Standard Deviation 2	0 score on a scale Standard Deviation 0	—	—	—
Brief Pain Inventory (BPI): Interference of Pain With Aspects of Life (General Activity) During Double-blind Treatment Period - Change From Baseline Day 7 (n=10, 3)	0 score on a scale Standard Deviation 2	0 score on a scale Standard Deviation 0	—	—	—

SECONDARY outcome

Timeframe: At baseline and Day 49 during the post-treatment observation period

Population: Participants who provided baseline data and at least one other data point for this outcome measure.

Participants rated the degree to which their pain interfered with various daily functions by using the BPI short form. Interference with general activity was rated on a scale from 0 (does not interfere) to 10 (completely interferes). Baseline was defined as the most recent value obtained prior to the start of the dosing on Day 1 of the double-blind dosing period.

Outcome measures

Measure	Treatment With Study Product n=8 Participants Participants randomized 3:1 (Aes-103 to placebo) to receive 4 times daily dosing of 1,000 mg of Aes-103 for 28 days	Treatment With Placebo n=2 Participants Participants randomized 3:1 (Aes-103 to placebo) to receive 4 times daily dosing of 1,000 mg of placebo for 28 days	All Treated Participants All participants randomized 3:1 (Aes-103 to placebo) and received 4 times daily dosing of 1,000 mg AEs-103 or 1,000 mg of placebo for 28 days	Post-treatment With Study Product Observation Period Participants underwent a post-treatment observation period of 21 days during which no study product (Aes-103) was received	Post-treatment With Placebo Observation Period Participants underwent a post-treatment observation period of 21 days during which no placebo was received
Brief Pain Inventory (BPI): Interference of Pain With Aspects of Life (General Activity) During Post-treatment Observation Period - Change From Baseline	0 score on a scale Standard Deviation 1	0 score on a scale Standard Deviation 0	—	—	—

SECONDARY outcome

Timeframe: Throughout the study period (approximately 9 weeks)

Population: Data not collected for this outcome measure. Study terminated early.

Analgesic use assessed with pain levels by numerical pain rating scale (NPRS) and brief pain inventory (BPI).

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Throughout the study period (approximately 9 weeks)

Population: Data not collected for this outcome measure. Study terminated early.

Outcome measures

Outcome data not reported

Adverse Events

Placebo lead-in Period

Serious events: 2 serious events

Other events: 21 other events

Deaths: 0 deaths

Double-blind Treatment Period

Serious events: 0 serious events

Other events: 12 other events

Deaths: 0 deaths

Post-treatment Observation Period

Serious events: 1 serious events

Other events: 4 other events

Deaths: 0 deaths

Serious adverse events

Measure	Placebo lead-in Period n=23 participants at risk Participants enrolled in a 14 day single-blind placebo lead-in received 4 times daily dosing of placebo (Day -14 to Day -1)	Double-blind Treatment Period n=14 participants at risk Participants randomized 3:1 (Aes-103 to placebo) to receive 4 times daily dosing of either 1,000 mg of Aes-103 (study product) or placebo for 28 days (Day 1 to Day 28)	Post-treatment Observation Period n=12 participants at risk Participants underwent a post-treatment observation period of 21 days during which no study product (Aes-103) or placebo was received (Day 29 to Day 49)
Congenital, familial and genetic disorders Sickle cell anaemia with crisis	8.7% 2/23 • Number of events 2 • Throughout study period (approximately 9 weeks) Summary tables for Adverse Events were provided per study period i.e. Placebo Lead-in Period, Double-blind treatment period and Post-treatment observation period. No breakdown of AEs with study product and placebo were provided as study terminated early.	0.00% 0/14 • Throughout study period (approximately 9 weeks) Summary tables for Adverse Events were provided per study period i.e. Placebo Lead-in Period, Double-blind treatment period and Post-treatment observation period. No breakdown of AEs with study product and placebo were provided as study terminated early.	0.00% 0/12 • Throughout study period (approximately 9 weeks) Summary tables for Adverse Events were provided per study period i.e. Placebo Lead-in Period, Double-blind treatment period and Post-treatment observation period. No breakdown of AEs with study product and placebo were provided as study terminated early.
Congenital, familial and genetic disorders Sickle cell anaemia	0.00% 0/23 • Throughout study period (approximately 9 weeks) Summary tables for Adverse Events were provided per study period i.e. Placebo Lead-in Period, Double-blind treatment period and Post-treatment observation period. No breakdown of AEs with study product and placebo were provided as study terminated early.	0.00% 0/14 • Throughout study period (approximately 9 weeks) Summary tables for Adverse Events were provided per study period i.e. Placebo Lead-in Period, Double-blind treatment period and Post-treatment observation period. No breakdown of AEs with study product and placebo were provided as study terminated early.	8.3% 1/12 • Number of events 1 • Throughout study period (approximately 9 weeks) Summary tables for Adverse Events were provided per study period i.e. Placebo Lead-in Period, Double-blind treatment period and Post-treatment observation period. No breakdown of AEs with study product and placebo were provided as study terminated early.

Other adverse events

Measure	Placebo lead-in Period n=23 participants at risk Participants enrolled in a 14 day single-blind placebo lead-in received 4 times daily dosing of placebo (Day -14 to Day -1)	Double-blind Treatment Period n=14 participants at risk Participants randomized 3:1 (Aes-103 to placebo) to receive 4 times daily dosing of either 1,000 mg of Aes-103 (study product) or placebo for 28 days (Day 1 to Day 28)	Post-treatment Observation Period n=12 participants at risk Participants underwent a post-treatment observation period of 21 days during which no study product (Aes-103) or placebo was received (Day 29 to Day 49)
Gastrointestinal disorders Abdominal discomfort	4.3% 1/23 • Number of events 1 • Throughout study period (approximately 9 weeks) Summary tables for Adverse Events were provided per study period i.e. Placebo Lead-in Period, Double-blind treatment period and Post-treatment observation period. No breakdown of AEs with study product and placebo were provided as study terminated early.	0.00% 0/14 • Throughout study period (approximately 9 weeks) Summary tables for Adverse Events were provided per study period i.e. Placebo Lead-in Period, Double-blind treatment period and Post-treatment observation period. No breakdown of AEs with study product and placebo were provided as study terminated early.	0.00% 0/12 • Throughout study period (approximately 9 weeks) Summary tables for Adverse Events were provided per study period i.e. Placebo Lead-in Period, Double-blind treatment period and Post-treatment observation period. No breakdown of AEs with study product and placebo were provided as study terminated early.
Gastrointestinal disorders Abdominal distension	4.3% 1/23 • Number of events 1 • Throughout study period (approximately 9 weeks) Summary tables for Adverse Events were provided per study period i.e. Placebo Lead-in Period, Double-blind treatment period and Post-treatment observation period. No breakdown of AEs with study product and placebo were provided as study terminated early.	0.00% 0/14 • Throughout study period (approximately 9 weeks) Summary tables for Adverse Events were provided per study period i.e. Placebo Lead-in Period, Double-blind treatment period and Post-treatment observation period. No breakdown of AEs with study product and placebo were provided as study terminated early.	0.00% 0/12 • Throughout study period (approximately 9 weeks) Summary tables for Adverse Events were provided per study period i.e. Placebo Lead-in Period, Double-blind treatment period and Post-treatment observation period. No breakdown of AEs with study product and placebo were provided as study terminated early.
Gastrointestinal disorders Abdominal pain	0.00% 0/23 • Throughout study period (approximately 9 weeks) Summary tables for Adverse Events were provided per study period i.e. Placebo Lead-in Period, Double-blind treatment period and Post-treatment observation period. No breakdown of AEs with study product and placebo were provided as study terminated early.	7.1% 1/14 • Number of events 1 • Throughout study period (approximately 9 weeks) Summary tables for Adverse Events were provided per study period i.e. Placebo Lead-in Period, Double-blind treatment period and Post-treatment observation period. No breakdown of AEs with study product and placebo were provided as study terminated early.	0.00% 0/12 • Throughout study period (approximately 9 weeks) Summary tables for Adverse Events were provided per study period i.e. Placebo Lead-in Period, Double-blind treatment period and Post-treatment observation period. No breakdown of AEs with study product and placebo were provided as study terminated early.
Gastrointestinal disorders Abdominal pain upper	8.7% 2/23 • Number of events 2 • Throughout study period (approximately 9 weeks) Summary tables for Adverse Events were provided per study period i.e. Placebo Lead-in Period, Double-blind treatment period and Post-treatment observation period. No breakdown of AEs with study product and placebo were provided as study terminated early.	0.00% 0/14 • Throughout study period (approximately 9 weeks) Summary tables for Adverse Events were provided per study period i.e. Placebo Lead-in Period, Double-blind treatment period and Post-treatment observation period. No breakdown of AEs with study product and placebo were provided as study terminated early.	0.00% 0/12 • Throughout study period (approximately 9 weeks) Summary tables for Adverse Events were provided per study period i.e. Placebo Lead-in Period, Double-blind treatment period and Post-treatment observation period. No breakdown of AEs with study product and placebo were provided as study terminated early.
Cardiac disorders Atrioventricular block first degree	0.00% 0/23 • Throughout study period (approximately 9 weeks) Summary tables for Adverse Events were provided per study period i.e. Placebo Lead-in Period, Double-blind treatment period and Post-treatment observation period. No breakdown of AEs with study product and placebo were provided as study terminated early.	7.1% 1/14 • Number of events 1 • Throughout study period (approximately 9 weeks) Summary tables for Adverse Events were provided per study period i.e. Placebo Lead-in Period, Double-blind treatment period and Post-treatment observation period. No breakdown of AEs with study product and placebo were provided as study terminated early.	0.00% 0/12 • Throughout study period (approximately 9 weeks) Summary tables for Adverse Events were provided per study period i.e. Placebo Lead-in Period, Double-blind treatment period and Post-treatment observation period. No breakdown of AEs with study product and placebo were provided as study terminated early.
Musculoskeletal and connective tissue disorders Back pain	4.3% 1/23 • Number of events 1 • Throughout study period (approximately 9 weeks) Summary tables for Adverse Events were provided per study period i.e. Placebo Lead-in Period, Double-blind treatment period and Post-treatment observation period. No breakdown of AEs with study product and placebo were provided as study terminated early.	7.1% 1/14 • Number of events 1 • Throughout study period (approximately 9 weeks) Summary tables for Adverse Events were provided per study period i.e. Placebo Lead-in Period, Double-blind treatment period and Post-treatment observation period. No breakdown of AEs with study product and placebo were provided as study terminated early.	0.00% 0/12 • Throughout study period (approximately 9 weeks) Summary tables for Adverse Events were provided per study period i.e. Placebo Lead-in Period, Double-blind treatment period and Post-treatment observation period. No breakdown of AEs with study product and placebo were provided as study terminated early.
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/23 • Throughout study period (approximately 9 weeks) Summary tables for Adverse Events were provided per study period i.e. Placebo Lead-in Period, Double-blind treatment period and Post-treatment observation period. No breakdown of AEs with study product and placebo were provided as study terminated early.	7.1% 1/14 • Number of events 1 • Throughout study period (approximately 9 weeks) Summary tables for Adverse Events were provided per study period i.e. Placebo Lead-in Period, Double-blind treatment period and Post-treatment observation period. No breakdown of AEs with study product and placebo were provided as study terminated early.	0.00% 0/12 • Throughout study period (approximately 9 weeks) Summary tables for Adverse Events were provided per study period i.e. Placebo Lead-in Period, Double-blind treatment period and Post-treatment observation period. No breakdown of AEs with study product and placebo were provided as study terminated early.
Gastrointestinal disorders Diarrhoea	4.3% 1/23 • Number of events 1 • Throughout study period (approximately 9 weeks) Summary tables for Adverse Events were provided per study period i.e. Placebo Lead-in Period, Double-blind treatment period and Post-treatment observation period. No breakdown of AEs with study product and placebo were provided as study terminated early.	7.1% 1/14 • Number of events 1 • Throughout study period (approximately 9 weeks) Summary tables for Adverse Events were provided per study period i.e. Placebo Lead-in Period, Double-blind treatment period and Post-treatment observation period. No breakdown of AEs with study product and placebo were provided as study terminated early.	0.00% 0/12 • Throughout study period (approximately 9 weeks) Summary tables for Adverse Events were provided per study period i.e. Placebo Lead-in Period, Double-blind treatment period and Post-treatment observation period. No breakdown of AEs with study product and placebo were provided as study terminated early.
Eye disorders Diplopia	0.00% 0/23 • Throughout study period (approximately 9 weeks) Summary tables for Adverse Events were provided per study period i.e. Placebo Lead-in Period, Double-blind treatment period and Post-treatment observation period. No breakdown of AEs with study product and placebo were provided as study terminated early.	7.1% 1/14 • Number of events 1 • Throughout study period (approximately 9 weeks) Summary tables for Adverse Events were provided per study period i.e. Placebo Lead-in Period, Double-blind treatment period and Post-treatment observation period. No breakdown of AEs with study product and placebo were provided as study terminated early.	0.00% 0/12 • Throughout study period (approximately 9 weeks) Summary tables for Adverse Events were provided per study period i.e. Placebo Lead-in Period, Double-blind treatment period and Post-treatment observation period. No breakdown of AEs with study product and placebo were provided as study terminated early.
Nervous system disorders Dysgeusia	56.5% 13/23 • Number of events 13 • Throughout study period (approximately 9 weeks) Summary tables for Adverse Events were provided per study period i.e. Placebo Lead-in Period, Double-blind treatment period and Post-treatment observation period. No breakdown of AEs with study product and placebo were provided as study terminated early.	7.1% 1/14 • Number of events 1 • Throughout study period (approximately 9 weeks) Summary tables for Adverse Events were provided per study period i.e. Placebo Lead-in Period, Double-blind treatment period and Post-treatment observation period. No breakdown of AEs with study product and placebo were provided as study terminated early.	0.00% 0/12 • Throughout study period (approximately 9 weeks) Summary tables for Adverse Events were provided per study period i.e. Placebo Lead-in Period, Double-blind treatment period and Post-treatment observation period. No breakdown of AEs with study product and placebo were provided as study terminated early.
Reproductive system and breast disorders Dysmenorrhoea	0.00% 0/23 • Throughout study period (approximately 9 weeks) Summary tables for Adverse Events were provided per study period i.e. Placebo Lead-in Period, Double-blind treatment period and Post-treatment observation period. No breakdown of AEs with study product and placebo were provided as study terminated early.	14.3% 2/14 • Number of events 2 • Throughout study period (approximately 9 weeks) Summary tables for Adverse Events were provided per study period i.e. Placebo Lead-in Period, Double-blind treatment period and Post-treatment observation period. No breakdown of AEs with study product and placebo were provided as study terminated early.	0.00% 0/12 • Throughout study period (approximately 9 weeks) Summary tables for Adverse Events were provided per study period i.e. Placebo Lead-in Period, Double-blind treatment period and Post-treatment observation period. No breakdown of AEs with study product and placebo were provided as study terminated early.
Gastrointestinal disorders Dyspepsia	4.3% 1/23 • Number of events 1 • Throughout study period (approximately 9 weeks) Summary tables for Adverse Events were provided per study period i.e. Placebo Lead-in Period, Double-blind treatment period and Post-treatment observation period. No breakdown of AEs with study product and placebo were provided as study terminated early.	0.00% 0/14 • Throughout study period (approximately 9 weeks) Summary tables for Adverse Events were provided per study period i.e. Placebo Lead-in Period, Double-blind treatment period and Post-treatment observation period. No breakdown of AEs with study product and placebo were provided as study terminated early.	0.00% 0/12 • Throughout study period (approximately 9 weeks) Summary tables for Adverse Events were provided per study period i.e. Placebo Lead-in Period, Double-blind treatment period and Post-treatment observation period. No breakdown of AEs with study product and placebo were provided as study terminated early.
Investigations Electrocardiogram T wave inversion	0.00% 0/23 • Throughout study period (approximately 9 weeks) Summary tables for Adverse Events were provided per study period i.e. Placebo Lead-in Period, Double-blind treatment period and Post-treatment observation period. No breakdown of AEs with study product and placebo were provided as study terminated early.	7.1% 1/14 • Number of events 1 • Throughout study period (approximately 9 weeks) Summary tables for Adverse Events were provided per study period i.e. Placebo Lead-in Period, Double-blind treatment period and Post-treatment observation period. No breakdown of AEs with study product and placebo were provided as study terminated early.	0.00% 0/12 • Throughout study period (approximately 9 weeks) Summary tables for Adverse Events were provided per study period i.e. Placebo Lead-in Period, Double-blind treatment period and Post-treatment observation period. No breakdown of AEs with study product and placebo were provided as study terminated early.
Gastrointestinal disorders Faeces discoloured	4.3% 1/23 • Number of events 1 • Throughout study period (approximately 9 weeks) Summary tables for Adverse Events were provided per study period i.e. Placebo Lead-in Period, Double-blind treatment period and Post-treatment observation period. No breakdown of AEs with study product and placebo were provided as study terminated early.	0.00% 0/14 • Throughout study period (approximately 9 weeks) Summary tables for Adverse Events were provided per study period i.e. Placebo Lead-in Period, Double-blind treatment period and Post-treatment observation period. No breakdown of AEs with study product and placebo were provided as study terminated early.	0.00% 0/12 • Throughout study period (approximately 9 weeks) Summary tables for Adverse Events were provided per study period i.e. Placebo Lead-in Period, Double-blind treatment period and Post-treatment observation period. No breakdown of AEs with study product and placebo were provided as study terminated early.
General disorders Fatigue	0.00% 0/23 • Throughout study period (approximately 9 weeks) Summary tables for Adverse Events were provided per study period i.e. Placebo Lead-in Period, Double-blind treatment period and Post-treatment observation period. No breakdown of AEs with study product and placebo were provided as study terminated early.	7.1% 1/14 • Number of events 2 • Throughout study period (approximately 9 weeks) Summary tables for Adverse Events were provided per study period i.e. Placebo Lead-in Period, Double-blind treatment period and Post-treatment observation period. No breakdown of AEs with study product and placebo were provided as study terminated early.	0.00% 0/12 • Throughout study period (approximately 9 weeks) Summary tables for Adverse Events were provided per study period i.e. Placebo Lead-in Period, Double-blind treatment period and Post-treatment observation period. No breakdown of AEs with study product and placebo were provided as study terminated early.
Gastrointestinal disorders Flatulence	4.3% 1/23 • Number of events 1 • Throughout study period (approximately 9 weeks) Summary tables for Adverse Events were provided per study period i.e. Placebo Lead-in Period, Double-blind treatment period and Post-treatment observation period. No breakdown of AEs with study product and placebo were provided as study terminated early.	0.00% 0/14 • Throughout study period (approximately 9 weeks) Summary tables for Adverse Events were provided per study period i.e. Placebo Lead-in Period, Double-blind treatment period and Post-treatment observation period. No breakdown of AEs with study product and placebo were provided as study terminated early.	0.00% 0/12 • Throughout study period (approximately 9 weeks) Summary tables for Adverse Events were provided per study period i.e. Placebo Lead-in Period, Double-blind treatment period and Post-treatment observation period. No breakdown of AEs with study product and placebo were provided as study terminated early.
Nervous system disorders Headache	21.7% 5/23 • Number of events 7 • Throughout study period (approximately 9 weeks) Summary tables for Adverse Events were provided per study period i.e. Placebo Lead-in Period, Double-blind treatment period and Post-treatment observation period. No breakdown of AEs with study product and placebo were provided as study terminated early.	42.9% 6/14 • Number of events 6 • Throughout study period (approximately 9 weeks) Summary tables for Adverse Events were provided per study period i.e. Placebo Lead-in Period, Double-blind treatment period and Post-treatment observation period. No breakdown of AEs with study product and placebo were provided as study terminated early.	8.3% 1/12 • Number of events 1 • Throughout study period (approximately 9 weeks) Summary tables for Adverse Events were provided per study period i.e. Placebo Lead-in Period, Double-blind treatment period and Post-treatment observation period. No breakdown of AEs with study product and placebo were provided as study terminated early.
Metabolism and nutrition disorders Increased appetite	8.7% 2/23 • Number of events 2 • Throughout study period (approximately 9 weeks) Summary tables for Adverse Events were provided per study period i.e. Placebo Lead-in Period, Double-blind treatment period and Post-treatment observation period. No breakdown of AEs with study product and placebo were provided as study terminated early.	0.00% 0/14 • Throughout study period (approximately 9 weeks) Summary tables for Adverse Events were provided per study period i.e. Placebo Lead-in Period, Double-blind treatment period and Post-treatment observation period. No breakdown of AEs with study product and placebo were provided as study terminated early.	0.00% 0/12 • Throughout study period (approximately 9 weeks) Summary tables for Adverse Events were provided per study period i.e. Placebo Lead-in Period, Double-blind treatment period and Post-treatment observation period. No breakdown of AEs with study product and placebo were provided as study terminated early.
Injury, poisoning and procedural complications Ligament sprain	0.00% 0/23 • Throughout study period (approximately 9 weeks) Summary tables for Adverse Events were provided per study period i.e. Placebo Lead-in Period, Double-blind treatment period and Post-treatment observation period. No breakdown of AEs with study product and placebo were provided as study terminated early.	7.1% 1/14 • Number of events 1 • Throughout study period (approximately 9 weeks) Summary tables for Adverse Events were provided per study period i.e. Placebo Lead-in Period, Double-blind treatment period and Post-treatment observation period. No breakdown of AEs with study product and placebo were provided as study terminated early.	0.00% 0/12 • Throughout study period (approximately 9 weeks) Summary tables for Adverse Events were provided per study period i.e. Placebo Lead-in Period, Double-blind treatment period and Post-treatment observation period. No breakdown of AEs with study product and placebo were provided as study terminated early.
Investigations Liver function test abnormal	4.3% 1/23 • Number of events 1 • Throughout study period (approximately 9 weeks) Summary tables for Adverse Events were provided per study period i.e. Placebo Lead-in Period, Double-blind treatment period and Post-treatment observation period. No breakdown of AEs with study product and placebo were provided as study terminated early.	0.00% 0/14 • Throughout study period (approximately 9 weeks) Summary tables for Adverse Events were provided per study period i.e. Placebo Lead-in Period, Double-blind treatment period and Post-treatment observation period. No breakdown of AEs with study product and placebo were provided as study terminated early.	0.00% 0/12 • Throughout study period (approximately 9 weeks) Summary tables for Adverse Events were provided per study period i.e. Placebo Lead-in Period, Double-blind treatment period and Post-treatment observation period. No breakdown of AEs with study product and placebo were provided as study terminated early.
Infections and infestations Lower respiratory tract infection	8.7% 2/23 • Number of events 2 • Throughout study period (approximately 9 weeks) Summary tables for Adverse Events were provided per study period i.e. Placebo Lead-in Period, Double-blind treatment period and Post-treatment observation period. No breakdown of AEs with study product and placebo were provided as study terminated early.	0.00% 0/14 • Throughout study period (approximately 9 weeks) Summary tables for Adverse Events were provided per study period i.e. Placebo Lead-in Period, Double-blind treatment period and Post-treatment observation period. No breakdown of AEs with study product and placebo were provided as study terminated early.	0.00% 0/12 • Throughout study period (approximately 9 weeks) Summary tables for Adverse Events were provided per study period i.e. Placebo Lead-in Period, Double-blind treatment period and Post-treatment observation period. No breakdown of AEs with study product and placebo were provided as study terminated early.
Nervous system disorders Migraine	4.3% 1/23 • Number of events 1 • Throughout study period (approximately 9 weeks) Summary tables for Adverse Events were provided per study period i.e. Placebo Lead-in Period, Double-blind treatment period and Post-treatment observation period. No breakdown of AEs with study product and placebo were provided as study terminated early.	0.00% 0/14 • Throughout study period (approximately 9 weeks) Summary tables for Adverse Events were provided per study period i.e. Placebo Lead-in Period, Double-blind treatment period and Post-treatment observation period. No breakdown of AEs with study product and placebo were provided as study terminated early.	8.3% 1/12 • Number of events 2 • Throughout study period (approximately 9 weeks) Summary tables for Adverse Events were provided per study period i.e. Placebo Lead-in Period, Double-blind treatment period and Post-treatment observation period. No breakdown of AEs with study product and placebo were provided as study terminated early.
Musculoskeletal and connective tissue disorders Muscle spasms	4.3% 1/23 • Number of events 1 • Throughout study period (approximately 9 weeks) Summary tables for Adverse Events were provided per study period i.e. Placebo Lead-in Period, Double-blind treatment period and Post-treatment observation period. No breakdown of AEs with study product and placebo were provided as study terminated early.	0.00% 0/14 • Throughout study period (approximately 9 weeks) Summary tables for Adverse Events were provided per study period i.e. Placebo Lead-in Period, Double-blind treatment period and Post-treatment observation period. No breakdown of AEs with study product and placebo were provided as study terminated early.	0.00% 0/12 • Throughout study period (approximately 9 weeks) Summary tables for Adverse Events were provided per study period i.e. Placebo Lead-in Period, Double-blind treatment period and Post-treatment observation period. No breakdown of AEs with study product and placebo were provided as study terminated early.
Musculoskeletal and connective tissue disorders Musculoskeletal stiffness	4.3% 1/23 • Number of events 1 • Throughout study period (approximately 9 weeks) Summary tables for Adverse Events were provided per study period i.e. Placebo Lead-in Period, Double-blind treatment period and Post-treatment observation period. No breakdown of AEs with study product and placebo were provided as study terminated early.	0.00% 0/14 • Throughout study period (approximately 9 weeks) Summary tables for Adverse Events were provided per study period i.e. Placebo Lead-in Period, Double-blind treatment period and Post-treatment observation period. No breakdown of AEs with study product and placebo were provided as study terminated early.	0.00% 0/12 • Throughout study period (approximately 9 weeks) Summary tables for Adverse Events were provided per study period i.e. Placebo Lead-in Period, Double-blind treatment period and Post-treatment observation period. No breakdown of AEs with study product and placebo were provided as study terminated early.
Gastrointestinal disorders Nausea	13.0% 3/23 • Number of events 3 • Throughout study period (approximately 9 weeks) Summary tables for Adverse Events were provided per study period i.e. Placebo Lead-in Period, Double-blind treatment period and Post-treatment observation period. No breakdown of AEs with study product and placebo were provided as study terminated early.	28.6% 4/14 • Number of events 4 • Throughout study period (approximately 9 weeks) Summary tables for Adverse Events were provided per study period i.e. Placebo Lead-in Period, Double-blind treatment period and Post-treatment observation period. No breakdown of AEs with study product and placebo were provided as study terminated early.	0.00% 0/12 • Throughout study period (approximately 9 weeks) Summary tables for Adverse Events were provided per study period i.e. Placebo Lead-in Period, Double-blind treatment period and Post-treatment observation period. No breakdown of AEs with study product and placebo were provided as study terminated early.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	4.3% 1/23 • Number of events 1 • Throughout study period (approximately 9 weeks) Summary tables for Adverse Events were provided per study period i.e. Placebo Lead-in Period, Double-blind treatment period and Post-treatment observation period. No breakdown of AEs with study product and placebo were provided as study terminated early.	7.1% 1/14 • Number of events 1 • Throughout study period (approximately 9 weeks) Summary tables for Adverse Events were provided per study period i.e. Placebo Lead-in Period, Double-blind treatment period and Post-treatment observation period. No breakdown of AEs with study product and placebo were provided as study terminated early.	0.00% 0/12 • Throughout study period (approximately 9 weeks) Summary tables for Adverse Events were provided per study period i.e. Placebo Lead-in Period, Double-blind treatment period and Post-treatment observation period. No breakdown of AEs with study product and placebo were provided as study terminated early.
General disorders Pain	4.3% 1/23 • Number of events 1 • Throughout study period (approximately 9 weeks) Summary tables for Adverse Events were provided per study period i.e. Placebo Lead-in Period, Double-blind treatment period and Post-treatment observation period. No breakdown of AEs with study product and placebo were provided as study terminated early.	7.1% 1/14 • Number of events 1 • Throughout study period (approximately 9 weeks) Summary tables for Adverse Events were provided per study period i.e. Placebo Lead-in Period, Double-blind treatment period and Post-treatment observation period. No breakdown of AEs with study product and placebo were provided as study terminated early.	0.00% 0/12 • Throughout study period (approximately 9 weeks) Summary tables for Adverse Events were provided per study period i.e. Placebo Lead-in Period, Double-blind treatment period and Post-treatment observation period. No breakdown of AEs with study product and placebo were provided as study terminated early.
Musculoskeletal and connective tissue disorders Pain in extremity	4.3% 1/23 • Number of events 1 • Throughout study period (approximately 9 weeks) Summary tables for Adverse Events were provided per study period i.e. Placebo Lead-in Period, Double-blind treatment period and Post-treatment observation period. No breakdown of AEs with study product and placebo were provided as study terminated early.	0.00% 0/14 • Throughout study period (approximately 9 weeks) Summary tables for Adverse Events were provided per study period i.e. Placebo Lead-in Period, Double-blind treatment period and Post-treatment observation period. No breakdown of AEs with study product and placebo were provided as study terminated early.	0.00% 0/12 • Throughout study period (approximately 9 weeks) Summary tables for Adverse Events were provided per study period i.e. Placebo Lead-in Period, Double-blind treatment period and Post-treatment observation period. No breakdown of AEs with study product and placebo were provided as study terminated early.
Infections and infestations Rhinitis	0.00% 0/23 • Throughout study period (approximately 9 weeks) Summary tables for Adverse Events were provided per study period i.e. Placebo Lead-in Period, Double-blind treatment period and Post-treatment observation period. No breakdown of AEs with study product and placebo were provided as study terminated early.	7.1% 1/14 • Number of events 1 • Throughout study period (approximately 9 weeks) Summary tables for Adverse Events were provided per study period i.e. Placebo Lead-in Period, Double-blind treatment period and Post-treatment observation period. No breakdown of AEs with study product and placebo were provided as study terminated early.	0.00% 0/12 • Throughout study period (approximately 9 weeks) Summary tables for Adverse Events were provided per study period i.e. Placebo Lead-in Period, Double-blind treatment period and Post-treatment observation period. No breakdown of AEs with study product and placebo were provided as study terminated early.
Congenital, familial and genetic disorders Sickle cell anaemia	21.7% 5/23 • Number of events 5 • Throughout study period (approximately 9 weeks) Summary tables for Adverse Events were provided per study period i.e. Placebo Lead-in Period, Double-blind treatment period and Post-treatment observation period. No breakdown of AEs with study product and placebo were provided as study terminated early.	35.7% 5/14 • Number of events 6 • Throughout study period (approximately 9 weeks) Summary tables for Adverse Events were provided per study period i.e. Placebo Lead-in Period, Double-blind treatment period and Post-treatment observation period. No breakdown of AEs with study product and placebo were provided as study terminated early.	16.7% 2/12 • Number of events 2 • Throughout study period (approximately 9 weeks) Summary tables for Adverse Events were provided per study period i.e. Placebo Lead-in Period, Double-blind treatment period and Post-treatment observation period. No breakdown of AEs with study product and placebo were provided as study terminated early.
Gastrointestinal disorders Toothache	4.3% 1/23 • Number of events 1 • Throughout study period (approximately 9 weeks) Summary tables for Adverse Events were provided per study period i.e. Placebo Lead-in Period, Double-blind treatment period and Post-treatment observation period. No breakdown of AEs with study product and placebo were provided as study terminated early.	7.1% 1/14 • Number of events 1 • Throughout study period (approximately 9 weeks) Summary tables for Adverse Events were provided per study period i.e. Placebo Lead-in Period, Double-blind treatment period and Post-treatment observation period. No breakdown of AEs with study product and placebo were provided as study terminated early.	8.3% 1/12 • Number of events 1 • Throughout study period (approximately 9 weeks) Summary tables for Adverse Events were provided per study period i.e. Placebo Lead-in Period, Double-blind treatment period and Post-treatment observation period. No breakdown of AEs with study product and placebo were provided as study terminated early.
Investigations Transaminases increased	0.00% 0/23 • Throughout study period (approximately 9 weeks) Summary tables for Adverse Events were provided per study period i.e. Placebo Lead-in Period, Double-blind treatment period and Post-treatment observation period. No breakdown of AEs with study product and placebo were provided as study terminated early.	7.1% 1/14 • Number of events 1 • Throughout study period (approximately 9 weeks) Summary tables for Adverse Events were provided per study period i.e. Placebo Lead-in Period, Double-blind treatment period and Post-treatment observation period. No breakdown of AEs with study product and placebo were provided as study terminated early.	0.00% 0/12 • Throughout study period (approximately 9 weeks) Summary tables for Adverse Events were provided per study period i.e. Placebo Lead-in Period, Double-blind treatment period and Post-treatment observation period. No breakdown of AEs with study product and placebo were provided as study terminated early.
Infections and infestations Upper respiratory tract infection	0.00% 0/23 • Throughout study period (approximately 9 weeks) Summary tables for Adverse Events were provided per study period i.e. Placebo Lead-in Period, Double-blind treatment period and Post-treatment observation period. No breakdown of AEs with study product and placebo were provided as study terminated early.	14.3% 2/14 • Number of events 2 • Throughout study period (approximately 9 weeks) Summary tables for Adverse Events were provided per study period i.e. Placebo Lead-in Period, Double-blind treatment period and Post-treatment observation period. No breakdown of AEs with study product and placebo were provided as study terminated early.	0.00% 0/12 • Throughout study period (approximately 9 weeks) Summary tables for Adverse Events were provided per study period i.e. Placebo Lead-in Period, Double-blind treatment period and Post-treatment observation period. No breakdown of AEs with study product and placebo were provided as study terminated early.
Gastrointestinal disorders Vomiting	4.3% 1/23 • Number of events 1 • Throughout study period (approximately 9 weeks) Summary tables for Adverse Events were provided per study period i.e. Placebo Lead-in Period, Double-blind treatment period and Post-treatment observation period. No breakdown of AEs with study product and placebo were provided as study terminated early.	7.1% 1/14 • Number of events 1 • Throughout study period (approximately 9 weeks) Summary tables for Adverse Events were provided per study period i.e. Placebo Lead-in Period, Double-blind treatment period and Post-treatment observation period. No breakdown of AEs with study product and placebo were provided as study terminated early.	0.00% 0/12 • Throughout study period (approximately 9 weeks) Summary tables for Adverse Events were provided per study period i.e. Placebo Lead-in Period, Double-blind treatment period and Post-treatment observation period. No breakdown of AEs with study product and placebo were provided as study terminated early.

Additional Information

Study Director

Shire

Phone: +1 866 842 5335

Email: ClinicalTransparency@shire.com

Results disclosure agreements

• Principal investigator is a sponsor employee Baxalta's agreements with PIs may vary per requirements of individual PI, but contain common elements. For this study, results may not be published without prior written approval of Sponsor.
• Publication restrictions are in place

Restriction type: OTHER