Trial Outcomes & Findings for Safety, Tolerability and Pharmacodynamics of SYNB1020 (NCT NCT03447730)

NCT ID: NCT03447730

Last Updated: 2021-05-13

Results Overview

Toxicity was graded in accordance with the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 4.03, as follows: Grade 1 (mild/asymptomatic; no intervention); Grade 2 (moderate; minimal intervention); Grade 3 (severe/medically significant; hospitalization indicated; disabling); Grade 4 (life-threatening; urgent intervention required). Adverse events (AEs) were reported based on clinical laboratory tests, vital sign and weight measurements, physical examinations, and any other medically indicated assessments, including subject interviews, from the time informed consent was signed through the end of the safety follow-up period. AEs were considered to be treatment emergent adverse events (TEAEs) if they occurred or worsened in severity after the first dose of study treatment. TEAEs were considered treatment-related if relationship to study drug was possibly related, probably related, definitely related, or a missing relationship.

• Recruitment status: TERMINATED
• Study phase: PHASE1/PHASE2
• Target enrollment: 23 participants
• Primary outcome timeframe: Up to 70 days
• Results posted on: 2021-05-13

Participant Flow

Participant milestones

Measure	Part 1: SYNB1020 Part 1 comprised a sentinel open-label cohort of subjects enrolled sequentially to receive SYNB1020, which was administered orally at a dose of 5 × 10\^11 colony-forming units (CFU) 3 times daily (TID) given immediately after meals from Days 1 through 6.	Part 2: SYNB1020 Subjects randomized to receive SYNB1020 in Part 2 received SYNB1020 administered orally at a dose of 5 × 10\^11 CFU TID given immediately after meals from Days 1 through 6.	Part 2: Placebo Subjects randomized to receive control in Part 2 received matching placebo (100 mL masking solution) administered orally TID given immediately after meals from Days 1 through 6.
Overall Study STARTED	6	9	8
Overall Study COMPLETED	6	7	8
Overall Study NOT COMPLETED	0	2	0

Reasons for withdrawal

Measure	Part 1: SYNB1020 Part 1 comprised a sentinel open-label cohort of subjects enrolled sequentially to receive SYNB1020, which was administered orally at a dose of 5 × 10\^11 colony-forming units (CFU) 3 times daily (TID) given immediately after meals from Days 1 through 6.	Part 2: SYNB1020 Subjects randomized to receive SYNB1020 in Part 2 received SYNB1020 administered orally at a dose of 5 × 10\^11 CFU TID given immediately after meals from Days 1 through 6.	Part 2: Placebo Subjects randomized to receive control in Part 2 received matching placebo (100 mL masking solution) administered orally TID given immediately after meals from Days 1 through 6.
Overall Study Adverse Event	0	2	0

Baseline Characteristics

Safety, Tolerability and Pharmacodynamics of SYNB1020

Baseline characteristics by cohort

Measure	Part 1: SYNB1020 n=6 Participants Part 1 comprised a sentinel open-label cohort of subjects enrolled sequentially to receive SYNB1020, which was administered orally at a dose of 5 × 10\^11 CFU TID given immediately after meals from Days 1 through 6.	Part 2: SYNB1020 n=9 Participants Subjects randomized to receive SYNB1020 in Part 2 received SYNB1020 administered orally at a dose of 5 × 10\^11 CFU TID given immediately after meals from Days 1 through 6.	Part 2: Placebo n=8 Participants Subjects randomized to receive control in Part 2 received matching placebo (100 mL masking solution) administered orally TID given immediately after meals from Days 1 through 6.	Total n=23 Participants Total of all reporting groups
Age, Continuous	54.5 years n=5 Participants	57.0 years n=7 Participants	59.5 years n=5 Participants	58.0 years n=4 Participants
Sex: Female, Male Female	2 Participants n=5 Participants	4 Participants n=7 Participants	1 Participants n=5 Participants	7 Participants n=4 Participants
Sex: Female, Male Male	4 Participants n=5 Participants	5 Participants n=7 Participants	7 Participants n=5 Participants	16 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	3 Participants n=5 Participants	4 Participants n=7 Participants	6 Participants n=5 Participants	13 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	3 Participants n=5 Participants	5 Participants n=7 Participants	2 Participants n=5 Participants	10 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) White	6 Participants n=5 Participants	9 Participants n=7 Participants	8 Participants n=5 Participants	23 Participants n=4 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Region of Enrollment United States	6 participants n=5 Participants	9 participants n=7 Participants	8 participants n=5 Participants	23 participants n=4 Participants

PRIMARY outcome

Timeframe: Up to 70 days

Population: All subjects who received at least 1 dose of SYNB1020 or placebo

Toxicity was graded in accordance with the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 4.03, as follows: Grade 1 (mild/asymptomatic; no intervention); Grade 2 (moderate; minimal intervention); Grade 3 (severe/medically significant; hospitalization indicated; disabling); Grade 4 (life-threatening; urgent intervention required). Adverse events (AEs) were reported based on clinical laboratory tests, vital sign and weight measurements, physical examinations, and any other medically indicated assessments, including subject interviews, from the time informed consent was signed through the end of the safety follow-up period. AEs were considered to be treatment emergent adverse events (TEAEs) if they occurred or worsened in severity after the first dose of study treatment. TEAEs were considered treatment-related if relationship to study drug was possibly related, probably related, definitely related, or a missing relationship.

Outcome measures

Measure	Part 1: SYNB1020 n=6 Participants Part 1 comprised a sentinel open-label cohort of subjects enrolled sequentially to receive SYNB1020, which was administered orally at a dose of 5 × 10\^11 CFU TID given immediately after meals from Days 1 through 6.	Part 2: SYNB1020 n=9 Participants Subjects randomized to receive SYNB1020 in Part 2 received SYNB1020 administered orally at a dose of 5 × 10\^11 CFU TID given immediately after meals from Days 1 through 6.	Part 2: Placebo n=8 Participants Subjects randomized to receive control in Part 2 received matching placebo (100 mL masking solution) administered orally TID given immediately after meals from Days 1 through 6.
Number of Participants With Treatment-Emergent Adverse Events Maximum TEAE severity Grade 3	0 participants	0 participants	1 participants
Number of Participants With Treatment-Emergent Adverse Events Treatment-related TEAE	2 participants	4 participants	0 participants
Number of Participants With Treatment-Emergent Adverse Events Treatment-related TEAE leading to discontinuation	0 participants	0 participants	0 participants
Number of Participants With Treatment-Emergent Adverse Events Serious TEAE	0 participants	0 participants	1 participants
Number of Participants With Treatment-Emergent Adverse Events Any TEAE	4 participants	8 participants	4 participants
Number of Participants With Treatment-Emergent Adverse Events Maximum TEAE severity Grade 1	3 participants	3 participants	1 participants
Number of Participants With Treatment-Emergent Adverse Events Maximum TEAE severity Grade 2	1 participants	5 participants	2 participants
Number of Participants With Treatment-Emergent Adverse Events TEAE leading to discontinuation	0 participants	2 participants	0 participants
Number of Participants With Treatment-Emergent Adverse Events Treatment-related Serious TEAE	0 participants	0 participants	0 participants
Number of Participants With Treatment-Emergent Adverse Events TEAE leading to death	0 participants	0 participants	0 participants

SECONDARY outcome

Timeframe: Up to 65 days

Population: All subjects who received at least 1 dose of SYNB1020 or placebo

SYNB1020 transit through the gastrointestinal tract was measured with qualitative and quantitative polymerase chain reaction (PCR) fecal assays from fecal samples collected at baseline, daily during the dosing period (Days 1 through 6), at the time of discharge from the inpatient unit (Day 7), and at follow-up visits beginning 7±1 days after the last dose and continuing biweekly until a subject had a negative SYNB1020 fecal test. SYNB1020 clearance reflects a test value of below the limit of quantitation (BLQ) occurring after the indicated number of days following the last dose of study treatment.

Outcome measures

Measure	Part 1: SYNB1020 n=6 Participants Part 1 comprised a sentinel open-label cohort of subjects enrolled sequentially to receive SYNB1020, which was administered orally at a dose of 5 × 10\^11 CFU TID given immediately after meals from Days 1 through 6.	Part 2: SYNB1020 n=9 Participants Subjects randomized to receive SYNB1020 in Part 2 received SYNB1020 administered orally at a dose of 5 × 10\^11 CFU TID given immediately after meals from Days 1 through 6.	Part 2: Placebo n=8 Participants Subjects randomized to receive control in Part 2 received matching placebo (100 mL masking solution) administered orally TID given immediately after meals from Days 1 through 6.
Number of Participants With Clearance of SYNB1020 From Feces SYNB1020 presence not detected	0 Participants	0 Participants	8 Participants
Number of Participants With Clearance of SYNB1020 From Feces Cleared by 25 days after last dose	6 Participants	9 Participants	0 Participants

SECONDARY outcome

Timeframe: Up to 9 days

Population: All subjects who received at least 1 dose of SYNB1020 or placebo, completed the study, and were considered evaluable for analysis of pharmacodynamic data

Fasting spot venous ammonia was collected at baseline (Day -2) and at the time of discharge from the inpatient unit (Day 7).

Outcome measures

Measure	Part 1: SYNB1020 n=6 Participants Part 1 comprised a sentinel open-label cohort of subjects enrolled sequentially to receive SYNB1020, which was administered orally at a dose of 5 × 10\^11 CFU TID given immediately after meals from Days 1 through 6.	Part 2: SYNB1020 n=7 Participants Subjects randomized to receive SYNB1020 in Part 2 received SYNB1020 administered orally at a dose of 5 × 10\^11 CFU TID given immediately after meals from Days 1 through 6.	Part 2: Placebo n=8 Participants Subjects randomized to receive control in Part 2 received matching placebo (100 mL masking solution) administered orally TID given immediately after meals from Days 1 through 6.
Daily Fasting Spot Venous Ammonia Baseline	64.7 μmol/L Standard Deviation 25.00	82.0 μmol/L Standard Deviation 36.41	55.6 μmol/L Standard Deviation 18.18
Daily Fasting Spot Venous Ammonia End of Study/Day 7	62.3 μmol/L Standard Deviation 27.57	97.7 μmol/L Standard Deviation 58.79	67.9 μmol/L Standard Deviation 42.69

Adverse Events

Part 1: SYNB1020

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Part 2: SYNB1020

Serious events: 0 serious events

Other events: 8 other events

Deaths: 0 deaths

Part 2: Placebo

Serious events: 1 serious events

Other events: 3 other events

Deaths: 0 deaths

Serious adverse events

Measure	Part 1: SYNB1020 n=6 participants at risk Part 1 comprised a sentinel open-label cohort of subjects enrolled sequentially to receive SYNB1020, which was administered orally at a dose of 5 × 10\^11 CFU TID given immediately after meals from Days 1 through 6.	Part 2: SYNB1020 n=9 participants at risk Subjects randomized to receive SYNB1020 in Part 2 received SYNB1020 administered orally at a dose of 5 × 10\^11 CFU TID given immediately after meals from Days 1 through 6.	Part 2: Placebo n=8 participants at risk Subjects randomized to receive control in Part 2 received matching placebo (100 mL masking solution) administered orally TID given immediately after meals from Days 1 through 6.
Gastrointestinal disorders Oesophageal varices haemorrhage	0.00% 0/6 • All AEs occurring from the time a subject signs informed consent through the safety follow-up period (i.e.,up to 70 days) were documented, regardless of the causal relationship to study drug. AEs that occurred or worsened in severity after the first dose of study treatment were considered treatment emergent (i.e., TEAEs). AE documentation included duration (onset and resolution dates), severity using the NCI CTCAE (version 4.03), assessment of causality, seriousness, and whether specific action or therapy was required. In summaries, preferred terms are counted only once per subject at the maximum reported grade.	0.00% 0/9 • All AEs occurring from the time a subject signs informed consent through the safety follow-up period (i.e.,up to 70 days) were documented, regardless of the causal relationship to study drug. AEs that occurred or worsened in severity after the first dose of study treatment were considered treatment emergent (i.e., TEAEs). AE documentation included duration (onset and resolution dates), severity using the NCI CTCAE (version 4.03), assessment of causality, seriousness, and whether specific action or therapy was required. In summaries, preferred terms are counted only once per subject at the maximum reported grade.	12.5% 1/8 • Number of events 1 • All AEs occurring from the time a subject signs informed consent through the safety follow-up period (i.e.,up to 70 days) were documented, regardless of the causal relationship to study drug. AEs that occurred or worsened in severity after the first dose of study treatment were considered treatment emergent (i.e., TEAEs). AE documentation included duration (onset and resolution dates), severity using the NCI CTCAE (version 4.03), assessment of causality, seriousness, and whether specific action or therapy was required. In summaries, preferred terms are counted only once per subject at the maximum reported grade.

Other adverse events

Measure	Part 1: SYNB1020 n=6 participants at risk Part 1 comprised a sentinel open-label cohort of subjects enrolled sequentially to receive SYNB1020, which was administered orally at a dose of 5 × 10\^11 CFU TID given immediately after meals from Days 1 through 6.	Part 2: SYNB1020 n=9 participants at risk Subjects randomized to receive SYNB1020 in Part 2 received SYNB1020 administered orally at a dose of 5 × 10\^11 CFU TID given immediately after meals from Days 1 through 6.	Part 2: Placebo n=8 participants at risk Subjects randomized to receive control in Part 2 received matching placebo (100 mL masking solution) administered orally TID given immediately after meals from Days 1 through 6.
Gastrointestinal disorders Constipation	33.3% 2/6 • Number of events 2 • All AEs occurring from the time a subject signs informed consent through the safety follow-up period (i.e.,up to 70 days) were documented, regardless of the causal relationship to study drug. AEs that occurred or worsened in severity after the first dose of study treatment were considered treatment emergent (i.e., TEAEs). AE documentation included duration (onset and resolution dates), severity using the NCI CTCAE (version 4.03), assessment of causality, seriousness, and whether specific action or therapy was required. In summaries, preferred terms are counted only once per subject at the maximum reported grade.	44.4% 4/9 • Number of events 4 • All AEs occurring from the time a subject signs informed consent through the safety follow-up period (i.e.,up to 70 days) were documented, regardless of the causal relationship to study drug. AEs that occurred or worsened in severity after the first dose of study treatment were considered treatment emergent (i.e., TEAEs). AE documentation included duration (onset and resolution dates), severity using the NCI CTCAE (version 4.03), assessment of causality, seriousness, and whether specific action or therapy was required. In summaries, preferred terms are counted only once per subject at the maximum reported grade.	0.00% 0/8 • All AEs occurring from the time a subject signs informed consent through the safety follow-up period (i.e.,up to 70 days) were documented, regardless of the causal relationship to study drug. AEs that occurred or worsened in severity after the first dose of study treatment were considered treatment emergent (i.e., TEAEs). AE documentation included duration (onset and resolution dates), severity using the NCI CTCAE (version 4.03), assessment of causality, seriousness, and whether specific action or therapy was required. In summaries, preferred terms are counted only once per subject at the maximum reported grade.
Gastrointestinal disorders Nausea	33.3% 2/6 • Number of events 2 • All AEs occurring from the time a subject signs informed consent through the safety follow-up period (i.e.,up to 70 days) were documented, regardless of the causal relationship to study drug. AEs that occurred or worsened in severity after the first dose of study treatment were considered treatment emergent (i.e., TEAEs). AE documentation included duration (onset and resolution dates), severity using the NCI CTCAE (version 4.03), assessment of causality, seriousness, and whether specific action or therapy was required. In summaries, preferred terms are counted only once per subject at the maximum reported grade.	44.4% 4/9 • Number of events 4 • All AEs occurring from the time a subject signs informed consent through the safety follow-up period (i.e.,up to 70 days) were documented, regardless of the causal relationship to study drug. AEs that occurred or worsened in severity after the first dose of study treatment were considered treatment emergent (i.e., TEAEs). AE documentation included duration (onset and resolution dates), severity using the NCI CTCAE (version 4.03), assessment of causality, seriousness, and whether specific action or therapy was required. In summaries, preferred terms are counted only once per subject at the maximum reported grade.	0.00% 0/8 • All AEs occurring from the time a subject signs informed consent through the safety follow-up period (i.e.,up to 70 days) were documented, regardless of the causal relationship to study drug. AEs that occurred or worsened in severity after the first dose of study treatment were considered treatment emergent (i.e., TEAEs). AE documentation included duration (onset and resolution dates), severity using the NCI CTCAE (version 4.03), assessment of causality, seriousness, and whether specific action or therapy was required. In summaries, preferred terms are counted only once per subject at the maximum reported grade.
Gastrointestinal disorders Vomiting	50.0% 3/6 • Number of events 3 • All AEs occurring from the time a subject signs informed consent through the safety follow-up period (i.e.,up to 70 days) were documented, regardless of the causal relationship to study drug. AEs that occurred or worsened in severity after the first dose of study treatment were considered treatment emergent (i.e., TEAEs). AE documentation included duration (onset and resolution dates), severity using the NCI CTCAE (version 4.03), assessment of causality, seriousness, and whether specific action or therapy was required. In summaries, preferred terms are counted only once per subject at the maximum reported grade.	33.3% 3/9 • Number of events 3 • All AEs occurring from the time a subject signs informed consent through the safety follow-up period (i.e.,up to 70 days) were documented, regardless of the causal relationship to study drug. AEs that occurred or worsened in severity after the first dose of study treatment were considered treatment emergent (i.e., TEAEs). AE documentation included duration (onset and resolution dates), severity using the NCI CTCAE (version 4.03), assessment of causality, seriousness, and whether specific action or therapy was required. In summaries, preferred terms are counted only once per subject at the maximum reported grade.	0.00% 0/8 • All AEs occurring from the time a subject signs informed consent through the safety follow-up period (i.e.,up to 70 days) were documented, regardless of the causal relationship to study drug. AEs that occurred or worsened in severity after the first dose of study treatment were considered treatment emergent (i.e., TEAEs). AE documentation included duration (onset and resolution dates), severity using the NCI CTCAE (version 4.03), assessment of causality, seriousness, and whether specific action or therapy was required. In summaries, preferred terms are counted only once per subject at the maximum reported grade.
Gastrointestinal disorders Diarrhoea	16.7% 1/6 • Number of events 1 • All AEs occurring from the time a subject signs informed consent through the safety follow-up period (i.e.,up to 70 days) were documented, regardless of the causal relationship to study drug. AEs that occurred or worsened in severity after the first dose of study treatment were considered treatment emergent (i.e., TEAEs). AE documentation included duration (onset and resolution dates), severity using the NCI CTCAE (version 4.03), assessment of causality, seriousness, and whether specific action or therapy was required. In summaries, preferred terms are counted only once per subject at the maximum reported grade.	22.2% 2/9 • Number of events 2 • All AEs occurring from the time a subject signs informed consent through the safety follow-up period (i.e.,up to 70 days) were documented, regardless of the causal relationship to study drug. AEs that occurred or worsened in severity after the first dose of study treatment were considered treatment emergent (i.e., TEAEs). AE documentation included duration (onset and resolution dates), severity using the NCI CTCAE (version 4.03), assessment of causality, seriousness, and whether specific action or therapy was required. In summaries, preferred terms are counted only once per subject at the maximum reported grade.	12.5% 1/8 • Number of events 1 • All AEs occurring from the time a subject signs informed consent through the safety follow-up period (i.e.,up to 70 days) were documented, regardless of the causal relationship to study drug. AEs that occurred or worsened in severity after the first dose of study treatment were considered treatment emergent (i.e., TEAEs). AE documentation included duration (onset and resolution dates), severity using the NCI CTCAE (version 4.03), assessment of causality, seriousness, and whether specific action or therapy was required. In summaries, preferred terms are counted only once per subject at the maximum reported grade.
Gastrointestinal disorders Abdominal pain	0.00% 0/6 • All AEs occurring from the time a subject signs informed consent through the safety follow-up period (i.e.,up to 70 days) were documented, regardless of the causal relationship to study drug. AEs that occurred or worsened in severity after the first dose of study treatment were considered treatment emergent (i.e., TEAEs). AE documentation included duration (onset and resolution dates), severity using the NCI CTCAE (version 4.03), assessment of causality, seriousness, and whether specific action or therapy was required. In summaries, preferred terms are counted only once per subject at the maximum reported grade.	11.1% 1/9 • Number of events 1 • All AEs occurring from the time a subject signs informed consent through the safety follow-up period (i.e.,up to 70 days) were documented, regardless of the causal relationship to study drug. AEs that occurred or worsened in severity after the first dose of study treatment were considered treatment emergent (i.e., TEAEs). AE documentation included duration (onset and resolution dates), severity using the NCI CTCAE (version 4.03), assessment of causality, seriousness, and whether specific action or therapy was required. In summaries, preferred terms are counted only once per subject at the maximum reported grade.	0.00% 0/8 • All AEs occurring from the time a subject signs informed consent through the safety follow-up period (i.e.,up to 70 days) were documented, regardless of the causal relationship to study drug. AEs that occurred or worsened in severity after the first dose of study treatment were considered treatment emergent (i.e., TEAEs). AE documentation included duration (onset and resolution dates), severity using the NCI CTCAE (version 4.03), assessment of causality, seriousness, and whether specific action or therapy was required. In summaries, preferred terms are counted only once per subject at the maximum reported grade.
Gastrointestinal disorders Abdominal pain upper	0.00% 0/6 • All AEs occurring from the time a subject signs informed consent through the safety follow-up period (i.e.,up to 70 days) were documented, regardless of the causal relationship to study drug. AEs that occurred or worsened in severity after the first dose of study treatment were considered treatment emergent (i.e., TEAEs). AE documentation included duration (onset and resolution dates), severity using the NCI CTCAE (version 4.03), assessment of causality, seriousness, and whether specific action or therapy was required. In summaries, preferred terms are counted only once per subject at the maximum reported grade.	11.1% 1/9 • Number of events 1 • All AEs occurring from the time a subject signs informed consent through the safety follow-up period (i.e.,up to 70 days) were documented, regardless of the causal relationship to study drug. AEs that occurred or worsened in severity after the first dose of study treatment were considered treatment emergent (i.e., TEAEs). AE documentation included duration (onset and resolution dates), severity using the NCI CTCAE (version 4.03), assessment of causality, seriousness, and whether specific action or therapy was required. In summaries, preferred terms are counted only once per subject at the maximum reported grade.	0.00% 0/8 • All AEs occurring from the time a subject signs informed consent through the safety follow-up period (i.e.,up to 70 days) were documented, regardless of the causal relationship to study drug. AEs that occurred or worsened in severity after the first dose of study treatment were considered treatment emergent (i.e., TEAEs). AE documentation included duration (onset and resolution dates), severity using the NCI CTCAE (version 4.03), assessment of causality, seriousness, and whether specific action or therapy was required. In summaries, preferred terms are counted only once per subject at the maximum reported grade.
Gastrointestinal disorders Eructation	0.00% 0/6 • All AEs occurring from the time a subject signs informed consent through the safety follow-up period (i.e.,up to 70 days) were documented, regardless of the causal relationship to study drug. AEs that occurred or worsened in severity after the first dose of study treatment were considered treatment emergent (i.e., TEAEs). AE documentation included duration (onset and resolution dates), severity using the NCI CTCAE (version 4.03), assessment of causality, seriousness, and whether specific action or therapy was required. In summaries, preferred terms are counted only once per subject at the maximum reported grade.	11.1% 1/9 • Number of events 1 • All AEs occurring from the time a subject signs informed consent through the safety follow-up period (i.e.,up to 70 days) were documented, regardless of the causal relationship to study drug. AEs that occurred or worsened in severity after the first dose of study treatment were considered treatment emergent (i.e., TEAEs). AE documentation included duration (onset and resolution dates), severity using the NCI CTCAE (version 4.03), assessment of causality, seriousness, and whether specific action or therapy was required. In summaries, preferred terms are counted only once per subject at the maximum reported grade.	0.00% 0/8 • All AEs occurring from the time a subject signs informed consent through the safety follow-up period (i.e.,up to 70 days) were documented, regardless of the causal relationship to study drug. AEs that occurred or worsened in severity after the first dose of study treatment were considered treatment emergent (i.e., TEAEs). AE documentation included duration (onset and resolution dates), severity using the NCI CTCAE (version 4.03), assessment of causality, seriousness, and whether specific action or therapy was required. In summaries, preferred terms are counted only once per subject at the maximum reported grade.
Nervous system disorders Dizziness	16.7% 1/6 • Number of events 1 • All AEs occurring from the time a subject signs informed consent through the safety follow-up period (i.e.,up to 70 days) were documented, regardless of the causal relationship to study drug. AEs that occurred or worsened in severity after the first dose of study treatment were considered treatment emergent (i.e., TEAEs). AE documentation included duration (onset and resolution dates), severity using the NCI CTCAE (version 4.03), assessment of causality, seriousness, and whether specific action or therapy was required. In summaries, preferred terms are counted only once per subject at the maximum reported grade.	22.2% 2/9 • Number of events 2 • All AEs occurring from the time a subject signs informed consent through the safety follow-up period (i.e.,up to 70 days) were documented, regardless of the causal relationship to study drug. AEs that occurred or worsened in severity after the first dose of study treatment were considered treatment emergent (i.e., TEAEs). AE documentation included duration (onset and resolution dates), severity using the NCI CTCAE (version 4.03), assessment of causality, seriousness, and whether specific action or therapy was required. In summaries, preferred terms are counted only once per subject at the maximum reported grade.	0.00% 0/8 • All AEs occurring from the time a subject signs informed consent through the safety follow-up period (i.e.,up to 70 days) were documented, regardless of the causal relationship to study drug. AEs that occurred or worsened in severity after the first dose of study treatment were considered treatment emergent (i.e., TEAEs). AE documentation included duration (onset and resolution dates), severity using the NCI CTCAE (version 4.03), assessment of causality, seriousness, and whether specific action or therapy was required. In summaries, preferred terms are counted only once per subject at the maximum reported grade.
Nervous system disorders Headache	16.7% 1/6 • Number of events 1 • All AEs occurring from the time a subject signs informed consent through the safety follow-up period (i.e.,up to 70 days) were documented, regardless of the causal relationship to study drug. AEs that occurred or worsened in severity after the first dose of study treatment were considered treatment emergent (i.e., TEAEs). AE documentation included duration (onset and resolution dates), severity using the NCI CTCAE (version 4.03), assessment of causality, seriousness, and whether specific action or therapy was required. In summaries, preferred terms are counted only once per subject at the maximum reported grade.	22.2% 2/9 • Number of events 2 • All AEs occurring from the time a subject signs informed consent through the safety follow-up period (i.e.,up to 70 days) were documented, regardless of the causal relationship to study drug. AEs that occurred or worsened in severity after the first dose of study treatment were considered treatment emergent (i.e., TEAEs). AE documentation included duration (onset and resolution dates), severity using the NCI CTCAE (version 4.03), assessment of causality, seriousness, and whether specific action or therapy was required. In summaries, preferred terms are counted only once per subject at the maximum reported grade.	0.00% 0/8 • All AEs occurring from the time a subject signs informed consent through the safety follow-up period (i.e.,up to 70 days) were documented, regardless of the causal relationship to study drug. AEs that occurred or worsened in severity after the first dose of study treatment were considered treatment emergent (i.e., TEAEs). AE documentation included duration (onset and resolution dates), severity using the NCI CTCAE (version 4.03), assessment of causality, seriousness, and whether specific action or therapy was required. In summaries, preferred terms are counted only once per subject at the maximum reported grade.
Nervous system disorders Hepatic encephalopathy	0.00% 0/6 • All AEs occurring from the time a subject signs informed consent through the safety follow-up period (i.e.,up to 70 days) were documented, regardless of the causal relationship to study drug. AEs that occurred or worsened in severity after the first dose of study treatment were considered treatment emergent (i.e., TEAEs). AE documentation included duration (onset and resolution dates), severity using the NCI CTCAE (version 4.03), assessment of causality, seriousness, and whether specific action or therapy was required. In summaries, preferred terms are counted only once per subject at the maximum reported grade.	22.2% 2/9 • Number of events 2 • All AEs occurring from the time a subject signs informed consent through the safety follow-up period (i.e.,up to 70 days) were documented, regardless of the causal relationship to study drug. AEs that occurred or worsened in severity after the first dose of study treatment were considered treatment emergent (i.e., TEAEs). AE documentation included duration (onset and resolution dates), severity using the NCI CTCAE (version 4.03), assessment of causality, seriousness, and whether specific action or therapy was required. In summaries, preferred terms are counted only once per subject at the maximum reported grade.	0.00% 0/8 • All AEs occurring from the time a subject signs informed consent through the safety follow-up period (i.e.,up to 70 days) were documented, regardless of the causal relationship to study drug. AEs that occurred or worsened in severity after the first dose of study treatment were considered treatment emergent (i.e., TEAEs). AE documentation included duration (onset and resolution dates), severity using the NCI CTCAE (version 4.03), assessment of causality, seriousness, and whether specific action or therapy was required. In summaries, preferred terms are counted only once per subject at the maximum reported grade.
Nervous system disorders Tremor	0.00% 0/6 • All AEs occurring from the time a subject signs informed consent through the safety follow-up period (i.e.,up to 70 days) were documented, regardless of the causal relationship to study drug. AEs that occurred or worsened in severity after the first dose of study treatment were considered treatment emergent (i.e., TEAEs). AE documentation included duration (onset and resolution dates), severity using the NCI CTCAE (version 4.03), assessment of causality, seriousness, and whether specific action or therapy was required. In summaries, preferred terms are counted only once per subject at the maximum reported grade.	11.1% 1/9 • Number of events 1 • All AEs occurring from the time a subject signs informed consent through the safety follow-up period (i.e.,up to 70 days) were documented, regardless of the causal relationship to study drug. AEs that occurred or worsened in severity after the first dose of study treatment were considered treatment emergent (i.e., TEAEs). AE documentation included duration (onset and resolution dates), severity using the NCI CTCAE (version 4.03), assessment of causality, seriousness, and whether specific action or therapy was required. In summaries, preferred terms are counted only once per subject at the maximum reported grade.	0.00% 0/8 • All AEs occurring from the time a subject signs informed consent through the safety follow-up period (i.e.,up to 70 days) were documented, regardless of the causal relationship to study drug. AEs that occurred or worsened in severity after the first dose of study treatment were considered treatment emergent (i.e., TEAEs). AE documentation included duration (onset and resolution dates), severity using the NCI CTCAE (version 4.03), assessment of causality, seriousness, and whether specific action or therapy was required. In summaries, preferred terms are counted only once per subject at the maximum reported grade.
Infections and infestations Nasopharyngitis	0.00% 0/6 • All AEs occurring from the time a subject signs informed consent through the safety follow-up period (i.e.,up to 70 days) were documented, regardless of the causal relationship to study drug. AEs that occurred or worsened in severity after the first dose of study treatment were considered treatment emergent (i.e., TEAEs). AE documentation included duration (onset and resolution dates), severity using the NCI CTCAE (version 4.03), assessment of causality, seriousness, and whether specific action or therapy was required. In summaries, preferred terms are counted only once per subject at the maximum reported grade.	0.00% 0/9 • All AEs occurring from the time a subject signs informed consent through the safety follow-up period (i.e.,up to 70 days) were documented, regardless of the causal relationship to study drug. AEs that occurred or worsened in severity after the first dose of study treatment were considered treatment emergent (i.e., TEAEs). AE documentation included duration (onset and resolution dates), severity using the NCI CTCAE (version 4.03), assessment of causality, seriousness, and whether specific action or therapy was required. In summaries, preferred terms are counted only once per subject at the maximum reported grade.	12.5% 1/8 • Number of events 1 • All AEs occurring from the time a subject signs informed consent through the safety follow-up period (i.e.,up to 70 days) were documented, regardless of the causal relationship to study drug. AEs that occurred or worsened in severity after the first dose of study treatment were considered treatment emergent (i.e., TEAEs). AE documentation included duration (onset and resolution dates), severity using the NCI CTCAE (version 4.03), assessment of causality, seriousness, and whether specific action or therapy was required. In summaries, preferred terms are counted only once per subject at the maximum reported grade.
Infections and infestations Upper respiratory tract infection	16.7% 1/6 • Number of events 1 • All AEs occurring from the time a subject signs informed consent through the safety follow-up period (i.e.,up to 70 days) were documented, regardless of the causal relationship to study drug. AEs that occurred or worsened in severity after the first dose of study treatment were considered treatment emergent (i.e., TEAEs). AE documentation included duration (onset and resolution dates), severity using the NCI CTCAE (version 4.03), assessment of causality, seriousness, and whether specific action or therapy was required. In summaries, preferred terms are counted only once per subject at the maximum reported grade.	0.00% 0/9 • All AEs occurring from the time a subject signs informed consent through the safety follow-up period (i.e.,up to 70 days) were documented, regardless of the causal relationship to study drug. AEs that occurred or worsened in severity after the first dose of study treatment were considered treatment emergent (i.e., TEAEs). AE documentation included duration (onset and resolution dates), severity using the NCI CTCAE (version 4.03), assessment of causality, seriousness, and whether specific action or therapy was required. In summaries, preferred terms are counted only once per subject at the maximum reported grade.	0.00% 0/8 • All AEs occurring from the time a subject signs informed consent through the safety follow-up period (i.e.,up to 70 days) were documented, regardless of the causal relationship to study drug. AEs that occurred or worsened in severity after the first dose of study treatment were considered treatment emergent (i.e., TEAEs). AE documentation included duration (onset and resolution dates), severity using the NCI CTCAE (version 4.03), assessment of causality, seriousness, and whether specific action or therapy was required. In summaries, preferred terms are counted only once per subject at the maximum reported grade.
Infections and infestations Urinary tract infection	0.00% 0/6 • All AEs occurring from the time a subject signs informed consent through the safety follow-up period (i.e.,up to 70 days) were documented, regardless of the causal relationship to study drug. AEs that occurred or worsened in severity after the first dose of study treatment were considered treatment emergent (i.e., TEAEs). AE documentation included duration (onset and resolution dates), severity using the NCI CTCAE (version 4.03), assessment of causality, seriousness, and whether specific action or therapy was required. In summaries, preferred terms are counted only once per subject at the maximum reported grade.	0.00% 0/9 • All AEs occurring from the time a subject signs informed consent through the safety follow-up period (i.e.,up to 70 days) were documented, regardless of the causal relationship to study drug. AEs that occurred or worsened in severity after the first dose of study treatment were considered treatment emergent (i.e., TEAEs). AE documentation included duration (onset and resolution dates), severity using the NCI CTCAE (version 4.03), assessment of causality, seriousness, and whether specific action or therapy was required. In summaries, preferred terms are counted only once per subject at the maximum reported grade.	12.5% 1/8 • Number of events 1 • All AEs occurring from the time a subject signs informed consent through the safety follow-up period (i.e.,up to 70 days) were documented, regardless of the causal relationship to study drug. AEs that occurred or worsened in severity after the first dose of study treatment were considered treatment emergent (i.e., TEAEs). AE documentation included duration (onset and resolution dates), severity using the NCI CTCAE (version 4.03), assessment of causality, seriousness, and whether specific action or therapy was required. In summaries, preferred terms are counted only once per subject at the maximum reported grade.
Metabolism and nutrition disorders Dehydration	0.00% 0/6 • All AEs occurring from the time a subject signs informed consent through the safety follow-up period (i.e.,up to 70 days) were documented, regardless of the causal relationship to study drug. AEs that occurred or worsened in severity after the first dose of study treatment were considered treatment emergent (i.e., TEAEs). AE documentation included duration (onset and resolution dates), severity using the NCI CTCAE (version 4.03), assessment of causality, seriousness, and whether specific action or therapy was required. In summaries, preferred terms are counted only once per subject at the maximum reported grade.	22.2% 2/9 • Number of events 2 • All AEs occurring from the time a subject signs informed consent through the safety follow-up period (i.e.,up to 70 days) were documented, regardless of the causal relationship to study drug. AEs that occurred or worsened in severity after the first dose of study treatment were considered treatment emergent (i.e., TEAEs). AE documentation included duration (onset and resolution dates), severity using the NCI CTCAE (version 4.03), assessment of causality, seriousness, and whether specific action or therapy was required. In summaries, preferred terms are counted only once per subject at the maximum reported grade.	0.00% 0/8 • All AEs occurring from the time a subject signs informed consent through the safety follow-up period (i.e.,up to 70 days) were documented, regardless of the causal relationship to study drug. AEs that occurred or worsened in severity after the first dose of study treatment were considered treatment emergent (i.e., TEAEs). AE documentation included duration (onset and resolution dates), severity using the NCI CTCAE (version 4.03), assessment of causality, seriousness, and whether specific action or therapy was required. In summaries, preferred terms are counted only once per subject at the maximum reported grade.
Injury, poisoning and procedural complications Limb injury	0.00% 0/6 • All AEs occurring from the time a subject signs informed consent through the safety follow-up period (i.e.,up to 70 days) were documented, regardless of the causal relationship to study drug. AEs that occurred or worsened in severity after the first dose of study treatment were considered treatment emergent (i.e., TEAEs). AE documentation included duration (onset and resolution dates), severity using the NCI CTCAE (version 4.03), assessment of causality, seriousness, and whether specific action or therapy was required. In summaries, preferred terms are counted only once per subject at the maximum reported grade.	11.1% 1/9 • Number of events 1 • All AEs occurring from the time a subject signs informed consent through the safety follow-up period (i.e.,up to 70 days) were documented, regardless of the causal relationship to study drug. AEs that occurred or worsened in severity after the first dose of study treatment were considered treatment emergent (i.e., TEAEs). AE documentation included duration (onset and resolution dates), severity using the NCI CTCAE (version 4.03), assessment of causality, seriousness, and whether specific action or therapy was required. In summaries, preferred terms are counted only once per subject at the maximum reported grade.	0.00% 0/8 • All AEs occurring from the time a subject signs informed consent through the safety follow-up period (i.e.,up to 70 days) were documented, regardless of the causal relationship to study drug. AEs that occurred or worsened in severity after the first dose of study treatment were considered treatment emergent (i.e., TEAEs). AE documentation included duration (onset and resolution dates), severity using the NCI CTCAE (version 4.03), assessment of causality, seriousness, and whether specific action or therapy was required. In summaries, preferred terms are counted only once per subject at the maximum reported grade.
Injury, poisoning and procedural complications Post-traumatic pain	0.00% 0/6 • All AEs occurring from the time a subject signs informed consent through the safety follow-up period (i.e.,up to 70 days) were documented, regardless of the causal relationship to study drug. AEs that occurred or worsened in severity after the first dose of study treatment were considered treatment emergent (i.e., TEAEs). AE documentation included duration (onset and resolution dates), severity using the NCI CTCAE (version 4.03), assessment of causality, seriousness, and whether specific action or therapy was required. In summaries, preferred terms are counted only once per subject at the maximum reported grade.	11.1% 1/9 • Number of events 1 • All AEs occurring from the time a subject signs informed consent through the safety follow-up period (i.e.,up to 70 days) were documented, regardless of the causal relationship to study drug. AEs that occurred or worsened in severity after the first dose of study treatment were considered treatment emergent (i.e., TEAEs). AE documentation included duration (onset and resolution dates), severity using the NCI CTCAE (version 4.03), assessment of causality, seriousness, and whether specific action or therapy was required. In summaries, preferred terms are counted only once per subject at the maximum reported grade.	0.00% 0/8 • All AEs occurring from the time a subject signs informed consent through the safety follow-up period (i.e.,up to 70 days) were documented, regardless of the causal relationship to study drug. AEs that occurred or worsened in severity after the first dose of study treatment were considered treatment emergent (i.e., TEAEs). AE documentation included duration (onset and resolution dates), severity using the NCI CTCAE (version 4.03), assessment of causality, seriousness, and whether specific action or therapy was required. In summaries, preferred terms are counted only once per subject at the maximum reported grade.
Psychiatric disorders Insomnia	16.7% 1/6 • Number of events 1 • All AEs occurring from the time a subject signs informed consent through the safety follow-up period (i.e.,up to 70 days) were documented, regardless of the causal relationship to study drug. AEs that occurred or worsened in severity after the first dose of study treatment were considered treatment emergent (i.e., TEAEs). AE documentation included duration (onset and resolution dates), severity using the NCI CTCAE (version 4.03), assessment of causality, seriousness, and whether specific action or therapy was required. In summaries, preferred terms are counted only once per subject at the maximum reported grade.	0.00% 0/9 • All AEs occurring from the time a subject signs informed consent through the safety follow-up period (i.e.,up to 70 days) were documented, regardless of the causal relationship to study drug. AEs that occurred or worsened in severity after the first dose of study treatment were considered treatment emergent (i.e., TEAEs). AE documentation included duration (onset and resolution dates), severity using the NCI CTCAE (version 4.03), assessment of causality, seriousness, and whether specific action or therapy was required. In summaries, preferred terms are counted only once per subject at the maximum reported grade.	0.00% 0/8 • All AEs occurring from the time a subject signs informed consent through the safety follow-up period (i.e.,up to 70 days) were documented, regardless of the causal relationship to study drug. AEs that occurred or worsened in severity after the first dose of study treatment were considered treatment emergent (i.e., TEAEs). AE documentation included duration (onset and resolution dates), severity using the NCI CTCAE (version 4.03), assessment of causality, seriousness, and whether specific action or therapy was required. In summaries, preferred terms are counted only once per subject at the maximum reported grade.
Skin and subcutaneous tissue disorders Rash	0.00% 0/6 • All AEs occurring from the time a subject signs informed consent through the safety follow-up period (i.e.,up to 70 days) were documented, regardless of the causal relationship to study drug. AEs that occurred or worsened in severity after the first dose of study treatment were considered treatment emergent (i.e., TEAEs). AE documentation included duration (onset and resolution dates), severity using the NCI CTCAE (version 4.03), assessment of causality, seriousness, and whether specific action or therapy was required. In summaries, preferred terms are counted only once per subject at the maximum reported grade.	11.1% 1/9 • Number of events 1 • All AEs occurring from the time a subject signs informed consent through the safety follow-up period (i.e.,up to 70 days) were documented, regardless of the causal relationship to study drug. AEs that occurred or worsened in severity after the first dose of study treatment were considered treatment emergent (i.e., TEAEs). AE documentation included duration (onset and resolution dates), severity using the NCI CTCAE (version 4.03), assessment of causality, seriousness, and whether specific action or therapy was required. In summaries, preferred terms are counted only once per subject at the maximum reported grade.	0.00% 0/8 • All AEs occurring from the time a subject signs informed consent through the safety follow-up period (i.e.,up to 70 days) were documented, regardless of the causal relationship to study drug. AEs that occurred or worsened in severity after the first dose of study treatment were considered treatment emergent (i.e., TEAEs). AE documentation included duration (onset and resolution dates), severity using the NCI CTCAE (version 4.03), assessment of causality, seriousness, and whether specific action or therapy was required. In summaries, preferred terms are counted only once per subject at the maximum reported grade.

Additional Information

Andrew Marsh, Head Clinical Operations

Synlogic

Phone: 617-401-9975

Email: andrew.marsh@synlogictx.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place

Restriction type: LTE60