Trial Outcomes & Findings for ACX-362E [Ibezapolstat] for Oral Treatment of Clostridioides Difficile Infection (NCT NCT04247542)
NCT ID: NCT04247542
Last Updated: 2025-01-17
Results Overview
Percentage of patients with CC at the test of cure (TOC) visit on day 12. CC was defined as survival and the resolution of diarrhea in the 24-hour period immediately before end of treatment (EOT--day 10) that was maintained for 48 hours post EOT without a requirement for additional CDI treatment. Diarrhea was defined as 3 or more unformed bowel movements (UBMs) in a 24-hour period; fewer than 3 UBMs was considered as resolution of diarrhea. A UBM was defined as a Type 5, 6, or 7 bowel movement on the Bristol Stool Chart.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
53 participants
Primary outcome timeframe
12 days
Results posted on
2025-01-17
Participant Flow
Segment 2A, Ibezapolstat Open-Label Arm: 14 enrolled. Segment 2B, Vancomycin-Controlled Double-Blind: 39 enrolled.
Segment 2A: 4 participants failed screening. 10 participants proceeded to treatment. Segment 2A participants did not participate in Segment 2B. Segment 2B: 7 participants failed screening. 32 participants proceeded to randomization and treatment. Segment 2B did not include Segment 2A participants.
Participant milestones
| Measure |
Segment 2A: Ibezapolstat (ACX-362E) Open-Label Single-Arm
Participants with diarrhea caused by C. difficile were treated with ibezapolstat 450 mg orally (3 x 150 mg capsules) every 12 hours for 10 days. Study drug was administered with 240 mL water. Participants were followed for recurrence for 28±2 days, regardless of response to ibezapolstat. Safety, tolerability, and efficacy were assessed by the Trial Oversight Committee which then recommended early termination of this segment of the trial and advancement to the 2B Segment because the first 10 patients demonstrated clinical cure.
|
Segment 2B: Ibezapolstat Arm--Double-blind, Randomized, Active-controlled Clinical Segment
Participants with diarrhea caused by C. difficile who were randomized to this arm received 450 mg ibezapolstat (3 x 150 mg capsules) every 12 hours for 10 days with placebo every 12 hours for 10 days (to maintain blind). Participants were followed for 28±2 days for recurrence. Blinding was maintained by over-encapsulation.
|
Segment 2B: Vancomycin Arm--Double-blind, Randomized, Active-controlled Clinical Segment
Participants with diarrhea caused by C. difficile who were randomized to this arm received vancomycin every 6 hours (1 capsule 125 mg + 2 placebo capsules every 12 hours or 1 capsule 125 mg every 12 hours). Participants were followed for 28±2 days for recurrence. Blinding was maintained by over-encapsulation.
|
|---|---|---|---|
|
2A: Ibezapolstat Open-Label Single-Arm
STARTED
|
10
|
0
|
0
|
|
2A: Ibezapolstat Open-Label Single-Arm
COMPLETED
|
10
|
0
|
0
|
|
2A: Ibezapolstat Open-Label Single-Arm
NOT COMPLETED
|
0
|
0
|
0
|
|
2B: Double-Blind Active-Controlled
STARTED
|
0
|
18
|
14
|
|
2B: Double-Blind Active-Controlled
COMPLETED
|
0
|
16
|
13
|
|
2B: Double-Blind Active-Controlled
NOT COMPLETED
|
0
|
2
|
1
|
Reasons for withdrawal
| Measure |
Segment 2A: Ibezapolstat (ACX-362E) Open-Label Single-Arm
Participants with diarrhea caused by C. difficile were treated with ibezapolstat 450 mg orally (3 x 150 mg capsules) every 12 hours for 10 days. Study drug was administered with 240 mL water. Participants were followed for recurrence for 28±2 days, regardless of response to ibezapolstat. Safety, tolerability, and efficacy were assessed by the Trial Oversight Committee which then recommended early termination of this segment of the trial and advancement to the 2B Segment because the first 10 patients demonstrated clinical cure.
|
Segment 2B: Ibezapolstat Arm--Double-blind, Randomized, Active-controlled Clinical Segment
Participants with diarrhea caused by C. difficile who were randomized to this arm received 450 mg ibezapolstat (3 x 150 mg capsules) every 12 hours for 10 days with placebo every 12 hours for 10 days (to maintain blind). Participants were followed for 28±2 days for recurrence. Blinding was maintained by over-encapsulation.
|
Segment 2B: Vancomycin Arm--Double-blind, Randomized, Active-controlled Clinical Segment
Participants with diarrhea caused by C. difficile who were randomized to this arm received vancomycin every 6 hours (1 capsule 125 mg + 2 placebo capsules every 12 hours or 1 capsule 125 mg every 12 hours). Participants were followed for 28±2 days for recurrence. Blinding was maintained by over-encapsulation.
|
|---|---|---|---|
|
2B: Double-Blind Active-Controlled
Did not receive study drug
|
0
|
1
|
0
|
|
2B: Double-Blind Active-Controlled
Treatment completed but incorrectly recorded as discountinued.
|
0
|
1
|
1
|
Baseline Characteristics
Segment 2A participants did not participate in Segment 2B. Segment 2B took place after Segment 2A was completed.
Baseline characteristics by cohort
| Measure |
Segment 2A: Ibezapolstat (ACX-362E) Open-Label Single-Arm
n=10 Participants
Participants with diarrhea caused by C. difficile were treated with ibezapolstat 450 mg orally (3 x 150 mg capsules) every 12 hours for 10 days. Study drug was administered with 240 mL water. Participants were followed for recurrence for 28±2 days, regardless of response to ibezapolstat. Safety, tolerability, and efficacy were assessed by the Trial Oversight Committee which then recommended early termination of this segment of the trial and advancement to the 2B Segment because the first 10 patients demonstrated clinical cure.
|
Segment 2B: Ibezapolstat Arm--Double-blind, Randomized, Active-controlled Clinical Segment
n=18 Participants
Participants with diarrhea caused by C. difficile who were randomized to this arm received 450 mg ibezapolstat (3 x 150 mg capsules) every 12 hours for 10 days with placebo every 12 hours for 10 days (to maintain blind). Participants were followed for 28±2 days for recurrence. Blinding was maintained by over-encapsulation.
|
Segment 2B: Vancomycin Arm--Double-blind, Randomized, Active-controlled Clinical Segment
n=14 Participants
Participants with diarrhea caused by C. difficile who were randomized to this arm received vancomycin every 6 hours (1 capsule 125 mg + 2 placebo capsules every 12 hours or 1 capsule 125 mg every 12 hours). Participants were followed for 28±2 days for recurrence. Blinding was maintained by over-encapsulation.
|
Total
n=42 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
Segment 2A
|
49.5 years
n=10 Participants • Segment 2A participants did not participate in Segment 2B. Segment 2B took place after Segment 2A was completed.
|
—
|
—
|
49.5 years
n=10 Participants • Segment 2A participants did not participate in Segment 2B. Segment 2B took place after Segment 2A was completed.
|
|
Age, Continuous
Segment 2B
|
—
|
63.2 years
n=18 Participants • Segment 2A participants did not participate in Segment 2B. Segment 2B took place after Segment 2A was completed.
|
61.8 years
n=14 Participants • Segment 2A participants did not participate in Segment 2B. Segment 2B took place after Segment 2A was completed.
|
59.4 years
n=32 Participants • Segment 2A participants did not participate in Segment 2B. Segment 2B took place after Segment 2A was completed.
|
|
Sex: Female, Male
Female
|
5 Participants
n=10 Participants
|
15 Participants
n=18 Participants
|
11 Participants
n=14 Participants
|
31 Participants
n=42 Participants
|
|
Sex: Female, Male
Male
|
5 Participants
n=10 Participants
|
3 Participants
n=18 Participants
|
3 Participants
n=14 Participants
|
11 Participants
n=42 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
8 Participants
n=10 Participants
|
12 Participants
n=18 Participants
|
11 Participants
n=14 Participants
|
31 Participants
n=42 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
2 Participants
n=10 Participants
|
6 Participants
n=18 Participants
|
3 Participants
n=14 Participants
|
11 Participants
n=42 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=10 Participants
|
0 Participants
n=18 Participants
|
0 Participants
n=14 Participants
|
0 Participants
n=42 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=10 Participants
|
0 Participants
n=18 Participants
|
0 Participants
n=14 Participants
|
0 Participants
n=42 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=10 Participants
|
0 Participants
n=18 Participants
|
0 Participants
n=14 Participants
|
0 Participants
n=42 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=10 Participants
|
0 Participants
n=18 Participants
|
0 Participants
n=14 Participants
|
0 Participants
n=42 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=10 Participants
|
0 Participants
n=18 Participants
|
1 Participants
n=14 Participants
|
1 Participants
n=42 Participants
|
|
Race (NIH/OMB)
White
|
10 Participants
n=10 Participants
|
18 Participants
n=18 Participants
|
13 Participants
n=14 Participants
|
41 Participants
n=42 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=10 Participants
|
0 Participants
n=18 Participants
|
0 Participants
n=14 Participants
|
0 Participants
n=42 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=10 Participants
|
0 Participants
n=18 Participants
|
0 Participants
n=14 Participants
|
0 Participants
n=42 Participants
|
PRIMARY outcome
Timeframe: 12 daysPopulation: 10 participants were analyzed in the modified Intent-to-Treat (mITT) and Per Protocol (PP) populations. The mITT population includes all subjects who were treated and assessed at the TOC visit. The PP population consists of patients in the mITT population with no major protocol deviations.
Percentage of patients with CC at the test of cure (TOC) visit on day 12. CC was defined as survival and the resolution of diarrhea in the 24-hour period immediately before end of treatment (EOT--day 10) that was maintained for 48 hours post EOT without a requirement for additional CDI treatment. Diarrhea was defined as 3 or more unformed bowel movements (UBMs) in a 24-hour period; fewer than 3 UBMs was considered as resolution of diarrhea. A UBM was defined as a Type 5, 6, or 7 bowel movement on the Bristol Stool Chart.
Outcome measures
| Measure |
Segment 2A: Ibezapolstat (ACX-362E) Open-Label Single-Arm
n=10 Participants
Participants with diarrhea caused by C. difficile were treated with ibezapolstat 450 mg orally (3 x 150 mg capsules) every 12 hours for 10 days. Study drug was administered with 240 mL water. Participants were followed for recurrence for 28±2 days, regardless of response to ibezapolstat. Safety, tolerability, and efficacy were assessed by the Trial Oversight Committee which then recommended early termination of this segment of the trial and advancement to the 2B Segment because the first 10 patients demonstrated clinical cure.
|
Segment 2B: Vancomycin Arm--double-blind, Randomized, Active-controlled Clinical Segment
Participants with diarrhea caused by C. difficile who were randomized to this arm received vancomycin every 6 hours (1 capsule 125 mg + 2 placebo capsules every 12 hours or 1 capsule 125 mg every 12 hours). Participants were followed for 28±2 days for recurrence. Blinding was maintained by over-encapsulation.
|
|---|---|---|
|
Segment 2A: Clinical Cure (CC) of Clostridioides Difficile Infection (CDI) Per Protocol (PP)/Modified Intent-to-Treat (mITT) Population
CC at TOC, yes
|
10 Participants
|
—
|
|
Segment 2A: Clinical Cure (CC) of Clostridioides Difficile Infection (CDI) Per Protocol (PP)/Modified Intent-to-Treat (mITT) Population
CC at TOC, no
|
0 Participants
|
—
|
PRIMARY outcome
Timeframe: 12 daysPopulation: PP participants were those in the ITT population who had no major protocol deviations. The ITT population is defined as all randomized subjects, analyzed according to their randomized treatment assignment.
Percentage of patients with CC at the test of cure (TOC) visit on day 12. CC was defined as survival and the resolution of diarrhea in the 24-hour period immediately before end of treatment (EOT--day 10) that was maintained for 48 hours post EOT without a requirement for additional CDI treatment. Diarrhea was defined as 3 or more unformed bowel movements (UBMs) in a 24-hour period; fewer than 3 UBMs was considered as resolution of diarrhea. A UBM was defined as a Type 5, 6, or 7 bowel movement on the Bristol Stool Chart.
Outcome measures
| Measure |
Segment 2A: Ibezapolstat (ACX-362E) Open-Label Single-Arm
n=16 Participants
Participants with diarrhea caused by C. difficile were treated with ibezapolstat 450 mg orally (3 x 150 mg capsules) every 12 hours for 10 days. Study drug was administered with 240 mL water. Participants were followed for recurrence for 28±2 days, regardless of response to ibezapolstat. Safety, tolerability, and efficacy were assessed by the Trial Oversight Committee which then recommended early termination of this segment of the trial and advancement to the 2B Segment because the first 10 patients demonstrated clinical cure.
|
Segment 2B: Vancomycin Arm--double-blind, Randomized, Active-controlled Clinical Segment
n=14 Participants
Participants with diarrhea caused by C. difficile who were randomized to this arm received vancomycin every 6 hours (1 capsule 125 mg + 2 placebo capsules every 12 hours or 1 capsule 125 mg every 12 hours). Participants were followed for 28±2 days for recurrence. Blinding was maintained by over-encapsulation.
|
|---|---|---|
|
Segment 2B Per Protocol (PP) Population: Clinical Cure (CC) of Clostridioides Difficile Infection (CDI)
CC at TOC, yes
|
15 Participants
|
14 Participants
|
|
Segment 2B Per Protocol (PP) Population: Clinical Cure (CC) of Clostridioides Difficile Infection (CDI)
CC at TOC, no
|
1 Participants
|
0 Participants
|
PRIMARY outcome
Timeframe: 12 daysPopulation: ITT population is defined as all randomized subjects, analyzed according to their randomized treatment assignment.
Percentage of patients with CC at the test of cure (TOC) visit on day 12. CC was defined as survival and the resolution of diarrhea in the 24-hour period immediately before end of treatment (EOT--day 10) that was maintained for 48 hours post EOT without a requirement for additional CDI treatment. Diarrhea was defined as 3 or more unformed bowel movements (UBMs) in a 24-hour period; fewer than 3 UBMs was considered as resolution of diarrhea. A UBM was defined as a Type 5, 6, or 7 bowel movement on the Bristol Stool Chart.
Outcome measures
| Measure |
Segment 2A: Ibezapolstat (ACX-362E) Open-Label Single-Arm
n=18 Participants
Participants with diarrhea caused by C. difficile were treated with ibezapolstat 450 mg orally (3 x 150 mg capsules) every 12 hours for 10 days. Study drug was administered with 240 mL water. Participants were followed for recurrence for 28±2 days, regardless of response to ibezapolstat. Safety, tolerability, and efficacy were assessed by the Trial Oversight Committee which then recommended early termination of this segment of the trial and advancement to the 2B Segment because the first 10 patients demonstrated clinical cure.
|
Segment 2B: Vancomycin Arm--double-blind, Randomized, Active-controlled Clinical Segment
n=14 Participants
Participants with diarrhea caused by C. difficile who were randomized to this arm received vancomycin every 6 hours (1 capsule 125 mg + 2 placebo capsules every 12 hours or 1 capsule 125 mg every 12 hours). Participants were followed for 28±2 days for recurrence. Blinding was maintained by over-encapsulation.
|
|---|---|---|
|
Segment 2B Intent-to-Treat (ITT) Population: Clinical Cure (CC) of Clostridioides Difficile Infection (CDI)
CC at TOC, yes
|
15 Participants
|
14 Participants
|
|
Segment 2B Intent-to-Treat (ITT) Population: Clinical Cure (CC) of Clostridioides Difficile Infection (CDI)
CC at TOC missing
|
1 Participants
|
0 Participants
|
|
Segment 2B Intent-to-Treat (ITT) Population: Clinical Cure (CC) of Clostridioides Difficile Infection (CDI)
CC at TOC, no
|
2 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: 38 daysPopulation: 10 participants were analyzed in the modified Intent-to-Treat (mITT) and Per Protocol (PP) populations. The mITT population includes all subjects who were treated and assessed at the TOC visit. The PP population consists of patients in the mITT population with no major protocol deviations.
Clinical cure (CC) at the test of cure (TOC) visit (ie, at least 48 hours after end of treatment \[day 10\]) and no recurrence within 28 days. Recurrence was defined as a new episode of diarrhea (3 or more UBMs in a 24-hour period) with a positive toxin result, using a Sponsor-approved C. difficile free toxin test and, in the opinion of the Investigator, requiring retreatment with an antibacterial agent for C. difficile.
Outcome measures
| Measure |
Segment 2A: Ibezapolstat (ACX-362E) Open-Label Single-Arm
n=10 Participants
Participants with diarrhea caused by C. difficile were treated with ibezapolstat 450 mg orally (3 x 150 mg capsules) every 12 hours for 10 days. Study drug was administered with 240 mL water. Participants were followed for recurrence for 28±2 days, regardless of response to ibezapolstat. Safety, tolerability, and efficacy were assessed by the Trial Oversight Committee which then recommended early termination of this segment of the trial and advancement to the 2B Segment because the first 10 patients demonstrated clinical cure.
|
Segment 2B: Vancomycin Arm--double-blind, Randomized, Active-controlled Clinical Segment
Participants with diarrhea caused by C. difficile who were randomized to this arm received vancomycin every 6 hours (1 capsule 125 mg + 2 placebo capsules every 12 hours or 1 capsule 125 mg every 12 hours). Participants were followed for 28±2 days for recurrence. Blinding was maintained by over-encapsulation.
|
|---|---|---|
|
Segment 2A: Sustained Clinical Cure (SCC) of Clostridioides Difficile Infection (CDI) Per Protocol (PP)/Modified Intent-to-Treat (mITT) Population
SCC, yes
|
10 Participants
|
—
|
|
Segment 2A: Sustained Clinical Cure (SCC) of Clostridioides Difficile Infection (CDI) Per Protocol (PP)/Modified Intent-to-Treat (mITT) Population
SCC, no
|
0 Participants
|
—
|
SECONDARY outcome
Timeframe: 38 daysPopulation: PP participants were those in the ITT population who had no major protocol deviations. The ITT population is defined as all randomized subjects, analyzed according to their randomized treatment assignment.
Clinical cure (CC) at the test of cure (TOC) visit (ie, at least 48 hours after end of treatment \[day 10\]) and no recurrence within 28 days. Recurrence was defined as a new episode of diarrhea (3 or more UBMs in a 24-hour period) with a positive toxin result, using a Sponsor-approved C. difficile free toxin test and, in the opinion of the Investigator, requiring retreatment with an antibacterial agent for C. difficile.
Outcome measures
| Measure |
Segment 2A: Ibezapolstat (ACX-362E) Open-Label Single-Arm
n=16 Participants
Participants with diarrhea caused by C. difficile were treated with ibezapolstat 450 mg orally (3 x 150 mg capsules) every 12 hours for 10 days. Study drug was administered with 240 mL water. Participants were followed for recurrence for 28±2 days, regardless of response to ibezapolstat. Safety, tolerability, and efficacy were assessed by the Trial Oversight Committee which then recommended early termination of this segment of the trial and advancement to the 2B Segment because the first 10 patients demonstrated clinical cure.
|
Segment 2B: Vancomycin Arm--double-blind, Randomized, Active-controlled Clinical Segment
n=14 Participants
Participants with diarrhea caused by C. difficile who were randomized to this arm received vancomycin every 6 hours (1 capsule 125 mg + 2 placebo capsules every 12 hours or 1 capsule 125 mg every 12 hours). Participants were followed for 28±2 days for recurrence. Blinding was maintained by over-encapsulation.
|
|---|---|---|
|
Segment 2B Per Protocol (PP) Population: Sustained Clinical Cure (SCC) of Clostridioides Difficile Infection (CDI)
SCC, yes
|
15 Participants
|
12 Participants
|
|
Segment 2B Per Protocol (PP) Population: Sustained Clinical Cure (SCC) of Clostridioides Difficile Infection (CDI)
SCC, no
|
1 Participants
|
2 Participants
|
SECONDARY outcome
Timeframe: 38 daysPopulation: ITT population is defined as all randomized subjects, analyzed according to their randomized treatment assignment.
Clinical cure (CC) at the test of cure (TOC) visit (ie, at least 48 hours after end of treatment \[day 10\]) and no recurrence within 28 days. Recurrence was defined as a new episode of diarrhea (3 or more UBMs in a 24-hour period) with a positive toxin result, using a Sponsor-approved C. difficile free toxin test and, in the opinion of the Investigator, requiring retreatment with an antibacterial agent for C. difficile.
Outcome measures
| Measure |
Segment 2A: Ibezapolstat (ACX-362E) Open-Label Single-Arm
n=18 Participants
Participants with diarrhea caused by C. difficile were treated with ibezapolstat 450 mg orally (3 x 150 mg capsules) every 12 hours for 10 days. Study drug was administered with 240 mL water. Participants were followed for recurrence for 28±2 days, regardless of response to ibezapolstat. Safety, tolerability, and efficacy were assessed by the Trial Oversight Committee which then recommended early termination of this segment of the trial and advancement to the 2B Segment because the first 10 patients demonstrated clinical cure.
|
Segment 2B: Vancomycin Arm--double-blind, Randomized, Active-controlled Clinical Segment
n=14 Participants
Participants with diarrhea caused by C. difficile who were randomized to this arm received vancomycin every 6 hours (1 capsule 125 mg + 2 placebo capsules every 12 hours or 1 capsule 125 mg every 12 hours). Participants were followed for 28±2 days for recurrence. Blinding was maintained by over-encapsulation.
|
|---|---|---|
|
Segment 2B Intent-to-Treat (ITT) Population: Sustained Clinical Cure (SCC) of Clostridioides Difficile Infection (CDI)
SCC, yes
|
15 Participants
|
12 Participants
|
|
Segment 2B Intent-to-Treat (ITT) Population: Sustained Clinical Cure (SCC) of Clostridioides Difficile Infection (CDI)
SCC missing
|
1 Participants
|
0 Participants
|
|
Segment 2B Intent-to-Treat (ITT) Population: Sustained Clinical Cure (SCC) of Clostridioides Difficile Infection (CDI)
SCC, no
|
2 Participants
|
2 Participants
|
SECONDARY outcome
Timeframe: Days 1, 5, and 10: 2 and 4 hours post-dosePopulation: 3 participants from the original population did not have plasma samples taken and were not included.
Plasma ibezapolstat concentrations were measured at specified day and time points following dose administration. Amount listed as zero not included in determination of Geometric Mean and CV%.
Outcome measures
| Measure |
Segment 2A: Ibezapolstat (ACX-362E) Open-Label Single-Arm
n=7 Participants
Participants with diarrhea caused by C. difficile were treated with ibezapolstat 450 mg orally (3 x 150 mg capsules) every 12 hours for 10 days. Study drug was administered with 240 mL water. Participants were followed for recurrence for 28±2 days, regardless of response to ibezapolstat. Safety, tolerability, and efficacy were assessed by the Trial Oversight Committee which then recommended early termination of this segment of the trial and advancement to the 2B Segment because the first 10 patients demonstrated clinical cure.
|
Segment 2B: Vancomycin Arm--double-blind, Randomized, Active-controlled Clinical Segment
Participants with diarrhea caused by C. difficile who were randomized to this arm received vancomycin every 6 hours (1 capsule 125 mg + 2 placebo capsules every 12 hours or 1 capsule 125 mg every 12 hours). Participants were followed for 28±2 days for recurrence. Blinding was maintained by over-encapsulation.
|
|---|---|---|
|
Segment 2A: Pharmacokinetics and Systemic Exposure to Ibezapolstat (ACX-362E), Plasma Concentrations
Day 1 Hour 2
|
114.32 ng/mL
Geometric Coefficient of Variation 249
|
—
|
|
Segment 2A: Pharmacokinetics and Systemic Exposure to Ibezapolstat (ACX-362E), Plasma Concentrations
Day 1 Hour 4
|
305.94 ng/mL
Geometric Coefficient of Variation 171
|
—
|
|
Segment 2A: Pharmacokinetics and Systemic Exposure to Ibezapolstat (ACX-362E), Plasma Concentrations
Day 5 Hour 2
|
185.37 ng/mL
Geometric Coefficient of Variation 244
|
—
|
|
Segment 2A: Pharmacokinetics and Systemic Exposure to Ibezapolstat (ACX-362E), Plasma Concentrations
Day 5 Hour 4
|
472.54 ng/mL
Geometric Coefficient of Variation 48.0
|
—
|
|
Segment 2A: Pharmacokinetics and Systemic Exposure to Ibezapolstat (ACX-362E), Plasma Concentrations
Day 10 Hour 2
|
152.02 ng/mL
Geometric Coefficient of Variation 227
|
—
|
|
Segment 2A: Pharmacokinetics and Systemic Exposure to Ibezapolstat (ACX-362E), Plasma Concentrations
Day 10 Hour 4
|
527.10 ng/mL
Geometric Coefficient of Variation 51.9
|
—
|
SECONDARY outcome
Timeframe: Days 1 and 5: 2 and 4 hours post-dosePopulation: 3 participants from the original population did not have plasma samples taken and were not included. 1 participant from the original population did not receive the study drug and was not included.
Plasma ibezapolstat concentrations were measured at specified day and time points following dose administration. Amount listed as zero not included in determination of Geometric Mean and CV%
Outcome measures
| Measure |
Segment 2A: Ibezapolstat (ACX-362E) Open-Label Single-Arm
n=14 Participants
Participants with diarrhea caused by C. difficile were treated with ibezapolstat 450 mg orally (3 x 150 mg capsules) every 12 hours for 10 days. Study drug was administered with 240 mL water. Participants were followed for recurrence for 28±2 days, regardless of response to ibezapolstat. Safety, tolerability, and efficacy were assessed by the Trial Oversight Committee which then recommended early termination of this segment of the trial and advancement to the 2B Segment because the first 10 patients demonstrated clinical cure.
|
Segment 2B: Vancomycin Arm--double-blind, Randomized, Active-controlled Clinical Segment
Participants with diarrhea caused by C. difficile who were randomized to this arm received vancomycin every 6 hours (1 capsule 125 mg + 2 placebo capsules every 12 hours or 1 capsule 125 mg every 12 hours). Participants were followed for 28±2 days for recurrence. Blinding was maintained by over-encapsulation.
|
|---|---|---|
|
Segment 2B: Pharmacokinetics and Systemic Exposure to Ibezapolstat (ACX-362E), Plasma Concentrations
Day 1 Hour 2
|
454.82 ng/mL
Geometric Coefficient of Variation 178
|
—
|
|
Segment 2B: Pharmacokinetics and Systemic Exposure to Ibezapolstat (ACX-362E), Plasma Concentrations
Day 1 Hour 4
|
268.07 ng/mL
Geometric Coefficient of Variation 128
|
—
|
|
Segment 2B: Pharmacokinetics and Systemic Exposure to Ibezapolstat (ACX-362E), Plasma Concentrations
Day 5 Hour 2
|
441.39 ng/mL
Geometric Coefficient of Variation 206
|
—
|
|
Segment 2B: Pharmacokinetics and Systemic Exposure to Ibezapolstat (ACX-362E), Plasma Concentrations
Day 5 Hour 4
|
358.52 ng/mL
Geometric Coefficient of Variation 151
|
—
|
SECONDARY outcome
Timeframe: Days -2, 3, 5, 8,10, 12, 20, 30, and 38Population: Participants with undetectable concentrations were not included in the data.
Fecal ibezapolstat concentrations were measured for specified days following dose administration. Specified days were 3, 5, 8, 10, 12, 20, and 38. Amount listed as zero not included in determination of Geometric Mean and CV%.
Outcome measures
| Measure |
Segment 2A: Ibezapolstat (ACX-362E) Open-Label Single-Arm
n=7 Participants
Participants with diarrhea caused by C. difficile were treated with ibezapolstat 450 mg orally (3 x 150 mg capsules) every 12 hours for 10 days. Study drug was administered with 240 mL water. Participants were followed for recurrence for 28±2 days, regardless of response to ibezapolstat. Safety, tolerability, and efficacy were assessed by the Trial Oversight Committee which then recommended early termination of this segment of the trial and advancement to the 2B Segment because the first 10 patients demonstrated clinical cure.
|
Segment 2B: Vancomycin Arm--double-blind, Randomized, Active-controlled Clinical Segment
Participants with diarrhea caused by C. difficile who were randomized to this arm received vancomycin every 6 hours (1 capsule 125 mg + 2 placebo capsules every 12 hours or 1 capsule 125 mg every 12 hours). Participants were followed for 28±2 days for recurrence. Blinding was maintained by over-encapsulation.
|
|---|---|---|
|
Segment 2A: Pharmacokinetics and Systemic Exposure to Ibezapolstat (ACX-362E), Fecal Concentrations
Day -2
|
NA µg/g
Geometric Coefficient of Variation NA
The measured amount was less than two observed concentration values greater than the lower limit of quantitation (LLOQ). The LLOQ is equal to 2.5 µg/g.
|
—
|
|
Segment 2A: Pharmacokinetics and Systemic Exposure to Ibezapolstat (ACX-362E), Fecal Concentrations
Day 3
|
285.88 µg/g
Geometric Coefficient of Variation 1058
|
—
|
|
Segment 2A: Pharmacokinetics and Systemic Exposure to Ibezapolstat (ACX-362E), Fecal Concentrations
Day 5
|
532.96 µg/g
Geometric Coefficient of Variation 1034
|
—
|
|
Segment 2A: Pharmacokinetics and Systemic Exposure to Ibezapolstat (ACX-362E), Fecal Concentrations
Day 8
|
943.87 µg/g
Geometric Coefficient of Variation 410
|
—
|
|
Segment 2A: Pharmacokinetics and Systemic Exposure to Ibezapolstat (ACX-362E), Fecal Concentrations
Day 10
|
1565.77 µg/g
Geometric Coefficient of Variation 271
|
—
|
|
Segment 2A: Pharmacokinetics and Systemic Exposure to Ibezapolstat (ACX-362E), Fecal Concentrations
Day 12
|
264.47 µg/g
Geometric Coefficient of Variation 1001
|
—
|
|
Segment 2A: Pharmacokinetics and Systemic Exposure to Ibezapolstat (ACX-362E), Fecal Concentrations
Day 20
|
53.52 µg/g
Geometric Coefficient of Variation 18317
|
—
|
|
Segment 2A: Pharmacokinetics and Systemic Exposure to Ibezapolstat (ACX-362E), Fecal Concentrations
Day 30
|
NA µg/g
Geometric Coefficient of Variation NA
The measured amount was less than two observed concentration values greater than the lower limit of quantitation (LLOQ). The LLOQ is equal to 2.5 µg/g.
|
—
|
|
Segment 2A: Pharmacokinetics and Systemic Exposure to Ibezapolstat (ACX-362E), Fecal Concentrations
Day 38
|
267.73 µg/g
Geometric Coefficient of Variation 24
|
—
|
SECONDARY outcome
Timeframe: Days -2, 3, 5, 8,10,12, 20, 30, and 38Population: Participants with undetectable concentrations were not included in the data.
Fecal ibezapolstat concentrations were measured for specified days following dose administration. Specified days were 3, 5, 8, 10, 12, and 20. Amount listed as zero not included in determination of Geometric Mean and CV%.
Outcome measures
| Measure |
Segment 2A: Ibezapolstat (ACX-362E) Open-Label Single-Arm
n=12 Participants
Participants with diarrhea caused by C. difficile were treated with ibezapolstat 450 mg orally (3 x 150 mg capsules) every 12 hours for 10 days. Study drug was administered with 240 mL water. Participants were followed for recurrence for 28±2 days, regardless of response to ibezapolstat. Safety, tolerability, and efficacy were assessed by the Trial Oversight Committee which then recommended early termination of this segment of the trial and advancement to the 2B Segment because the first 10 patients demonstrated clinical cure.
|
Segment 2B: Vancomycin Arm--double-blind, Randomized, Active-controlled Clinical Segment
Participants with diarrhea caused by C. difficile who were randomized to this arm received vancomycin every 6 hours (1 capsule 125 mg + 2 placebo capsules every 12 hours or 1 capsule 125 mg every 12 hours). Participants were followed for 28±2 days for recurrence. Blinding was maintained by over-encapsulation.
|
|---|---|---|
|
Segment 2B: Pharmacokinetics and Systemic Exposure to Ibezapolstat (ACX-362E), Fecal Concentrations
Day -2
|
NA µg/g
Geometric Coefficient of Variation NA
The measured amount was less than two observed concentration values greater than the lower limit of quantitation (LLOQ). The LLOQ is equal to 2.5 µg/g.
|
—
|
|
Segment 2B: Pharmacokinetics and Systemic Exposure to Ibezapolstat (ACX-362E), Fecal Concentrations
Day 3
|
411.4 µg/g
Geometric Coefficient of Variation 151
|
—
|
|
Segment 2B: Pharmacokinetics and Systemic Exposure to Ibezapolstat (ACX-362E), Fecal Concentrations
Day 5
|
407.65 µg/g
Geometric Coefficient of Variation 217
|
—
|
|
Segment 2B: Pharmacokinetics and Systemic Exposure to Ibezapolstat (ACX-362E), Fecal Concentrations
Day 8
|
716.21 µg/g
Geometric Coefficient of Variation 148
|
—
|
|
Segment 2B: Pharmacokinetics and Systemic Exposure to Ibezapolstat (ACX-362E), Fecal Concentrations
Day 10
|
958.15 µg/g
Geometric Coefficient of Variation 169
|
—
|
|
Segment 2B: Pharmacokinetics and Systemic Exposure to Ibezapolstat (ACX-362E), Fecal Concentrations
Day 12
|
250.52 µg/g
Geometric Coefficient of Variation 63.1
|
—
|
|
Segment 2B: Pharmacokinetics and Systemic Exposure to Ibezapolstat (ACX-362E), Fecal Concentrations
Day 20
|
12.74 µg/g
Geometric Coefficient of Variation 91.2
|
—
|
|
Segment 2B: Pharmacokinetics and Systemic Exposure to Ibezapolstat (ACX-362E), Fecal Concentrations
Day 30
|
NA µg/g
Geometric Coefficient of Variation NA
The measured amount was less than two observed concentration values greater than the lower limit of quantitation (LLOQ). The LLOQ is equal to 2.5 µg/g.
|
—
|
|
Segment 2B: Pharmacokinetics and Systemic Exposure to Ibezapolstat (ACX-362E), Fecal Concentrations
Day 38
|
NA µg/g
Geometric Coefficient of Variation NA
The measured amount was less than two observed concentration values greater than the lower limit of quantitation (LLOQ). The LLOQ is equal to 2.5 µg/g.
|
—
|
OTHER_PRE_SPECIFIED outcome
Timeframe: 10 daysPopulation: 10 participants were analyzed in the modified Intent-to-Treat (mITT) and Per Protocol (PP) populations. The mITT population includes all subjects who were treated and assessed at the TOC visit. The PP population consists of patients in the mITT population with no major protocol deviations.
Time in days from outset of treatment to the first formed bowel movement not followed within the next 24 hours by an unformed bowel movement (UBM), defined as a Type 5, 6, or 7 bowel movement on the Bristol Stool Chart.
Outcome measures
| Measure |
Segment 2A: Ibezapolstat (ACX-362E) Open-Label Single-Arm
n=10 Participants
Participants with diarrhea caused by C. difficile were treated with ibezapolstat 450 mg orally (3 x 150 mg capsules) every 12 hours for 10 days. Study drug was administered with 240 mL water. Participants were followed for recurrence for 28±2 days, regardless of response to ibezapolstat. Safety, tolerability, and efficacy were assessed by the Trial Oversight Committee which then recommended early termination of this segment of the trial and advancement to the 2B Segment because the first 10 patients demonstrated clinical cure.
|
Segment 2B: Vancomycin Arm--double-blind, Randomized, Active-controlled Clinical Segment
Participants with diarrhea caused by C. difficile who were randomized to this arm received vancomycin every 6 hours (1 capsule 125 mg + 2 placebo capsules every 12 hours or 1 capsule 125 mg every 12 hours). Participants were followed for 28±2 days for recurrence. Blinding was maintained by over-encapsulation.
|
|---|---|---|
|
Segment 2A: Time to Resolution of Diarrhea
|
5 Days to resolution of diarrhea
Interval 3.0 to 7.0
|
—
|
OTHER_PRE_SPECIFIED outcome
Timeframe: 40 daysPopulation: The Per Protocol (PP) population is represented here. PP participants were those in the intention-to-treat (ITT) population who had no major protocol deviations. The ITT population is defined as all randomized subjects, analyzed according to their randomized treatment assignment.
Time in days from outset of treatment to the first formed bowel movement not followed within the next 24 hours by an unformed bowel movement (UBM), defined as a Type 5, 6, or 7 bowel movement on the Bristol Stool Chart.
Outcome measures
| Measure |
Segment 2A: Ibezapolstat (ACX-362E) Open-Label Single-Arm
n=16 Participants
Participants with diarrhea caused by C. difficile were treated with ibezapolstat 450 mg orally (3 x 150 mg capsules) every 12 hours for 10 days. Study drug was administered with 240 mL water. Participants were followed for recurrence for 28±2 days, regardless of response to ibezapolstat. Safety, tolerability, and efficacy were assessed by the Trial Oversight Committee which then recommended early termination of this segment of the trial and advancement to the 2B Segment because the first 10 patients demonstrated clinical cure.
|
Segment 2B: Vancomycin Arm--double-blind, Randomized, Active-controlled Clinical Segment
n=14 Participants
Participants with diarrhea caused by C. difficile who were randomized to this arm received vancomycin every 6 hours (1 capsule 125 mg + 2 placebo capsules every 12 hours or 1 capsule 125 mg every 12 hours). Participants were followed for 28±2 days for recurrence. Blinding was maintained by over-encapsulation.
|
|---|---|---|
|
Segment 2B: Time to Resolution of Diarrhea
|
8 Days to resolution of diarrhea
Interval 4.0 to 10.0
|
9 Days to resolution of diarrhea
Interval 6.0 to 11.0
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Days 10 and 40Population: 8 of the 10 participants in Segment 2A provided stool samples and were analyzed. Not all 8 subjects were able to provide samples for all time points, so the data are not continuous. Data is reported as mean increase in biodiversity from the baseline.
The Shannon Diversity Index and Inverse Simpson Diversity Index are used to quantify biodiversity in a community like the gut microbiome, measuring how many different species are present in a community (richness) and how close in numbers different species in the community are to each other (evenness). The Shannon considers both factors while the Inverse Simpson focuses on evenness. The Shannon diversity index is calculated using natural logarithms, and units cancel out in the calculation, so it lacks units. It ranges from 0 to infinity. The Inverse Simpson represents the likelihood of selecting two different individuals from a population. It is a ratio and has no units. It ranges from 0 to 1. For both indexes, higher values indicate greater diversity.
Outcome measures
| Measure |
Segment 2A: Ibezapolstat (ACX-362E) Open-Label Single-Arm
n=8 Participants
Participants with diarrhea caused by C. difficile were treated with ibezapolstat 450 mg orally (3 x 150 mg capsules) every 12 hours for 10 days. Study drug was administered with 240 mL water. Participants were followed for recurrence for 28±2 days, regardless of response to ibezapolstat. Safety, tolerability, and efficacy were assessed by the Trial Oversight Committee which then recommended early termination of this segment of the trial and advancement to the 2B Segment because the first 10 patients demonstrated clinical cure.
|
Segment 2B: Vancomycin Arm--double-blind, Randomized, Active-controlled Clinical Segment
Participants with diarrhea caused by C. difficile who were randomized to this arm received vancomycin every 6 hours (1 capsule 125 mg + 2 placebo capsules every 12 hours or 1 capsule 125 mg every 12 hours). Participants were followed for 28±2 days for recurrence. Blinding was maintained by over-encapsulation.
|
|---|---|---|
|
Segment 2A: Microbiome Effects
Change from Baseline on Inverse Simpson Index, during treatment (until Day 10)
|
0.14 Index
Standard Deviation 0.06
|
—
|
|
Segment 2A: Microbiome Effects
Change from Baseline on Inverse Simpson Index, after treatment (until Day 40)
|
0.22 Index
Standard Deviation 0.10
|
—
|
|
Segment 2A: Microbiome Effects
Change from Baseline on Shannon Diversity Index, during treatment (until Day 10)
|
0.98 Index
Standard Deviation 0.48
|
—
|
|
Segment 2A: Microbiome Effects
Change from Baseline on Shannon Diversity Index, after treatment (until Day 40)
|
1.7 Index
Standard Deviation 0.87
|
—
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Days 12, 38, 66, and 94Population: PP participants were those in the intent-to-treat (ITT) population who had no major protocol deviations. The ITT population is defined as all randomized subjects, analyzed according to their randomized treatment assignment.
Change from baseline in each of the 5 dimensions of the EQ-5D-5L score, each scored on a scale of 1-5, with 1 being normal and 5 indicating extreme difficulty or impairment. The 5 dimensions are mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Summary Index Scores (the 5 dimensions combined into a single value) are reported here. Values for the index score ranges from -0.59 to 1, where 1 is the best possible health state.
Outcome measures
| Measure |
Segment 2A: Ibezapolstat (ACX-362E) Open-Label Single-Arm
n=16 Participants
Participants with diarrhea caused by C. difficile were treated with ibezapolstat 450 mg orally (3 x 150 mg capsules) every 12 hours for 10 days. Study drug was administered with 240 mL water. Participants were followed for recurrence for 28±2 days, regardless of response to ibezapolstat. Safety, tolerability, and efficacy were assessed by the Trial Oversight Committee which then recommended early termination of this segment of the trial and advancement to the 2B Segment because the first 10 patients demonstrated clinical cure.
|
Segment 2B: Vancomycin Arm--double-blind, Randomized, Active-controlled Clinical Segment
n=14 Participants
Participants with diarrhea caused by C. difficile who were randomized to this arm received vancomycin every 6 hours (1 capsule 125 mg + 2 placebo capsules every 12 hours or 1 capsule 125 mg every 12 hours). Participants were followed for 28±2 days for recurrence. Blinding was maintained by over-encapsulation.
|
|---|---|---|
|
Segment 2B Per Protocol (PP) Population: Change From Baseline in EuroQoL 5 Dimension 5 Level (EQ-5D-5L) Quality of Life Scores
Day 12
|
0.1667 Summary Index Score
Standard Deviation 0.1226
|
0.1611 Summary Index Score
Standard Deviation 0.1203
|
|
Segment 2B Per Protocol (PP) Population: Change From Baseline in EuroQoL 5 Dimension 5 Level (EQ-5D-5L) Quality of Life Scores
Day 38
|
0.1908 Summary Index Score
Standard Deviation 0.1379
|
0.1897 Summary Index Score
Standard Deviation 0.1506
|
|
Segment 2B Per Protocol (PP) Population: Change From Baseline in EuroQoL 5 Dimension 5 Level (EQ-5D-5L) Quality of Life Scores
Day 66
|
0.2677 Summary Index Score
Standard Deviation 0.1649
|
0.1964 Summary Index Score
Standard Deviation 0.1124
|
|
Segment 2B Per Protocol (PP) Population: Change From Baseline in EuroQoL 5 Dimension 5 Level (EQ-5D-5L) Quality of Life Scores
Day 94
|
0.2677 Summary Index Score
Standard Deviation 0.1649
|
0.2004 Summary Index Score
Standard Deviation 0.1158
|
OTHER_PRE_SPECIFIED outcome
Timeframe: 56 days after end of treatment (Day 66) and 84 days after end of treatment (Day 94)Population: Participants from the ITT population were recruited for an extended follow-up period. In the ITT extension population, 1 ibezapolstat subject failed at the CC (Day 12) and 1 vancomycin subject failed at the SCC (Day 38); both failures carried forward to both ECC evaluations. There were no failures post SCC (Day 38). In the ITT extension population who achieved a SCC, 5/5 ibezapolstat-treated participants and 7/7 vancomycin-treated participants experienced no infection recurrence.
Clinical cure (CC) at the test of cure (TOC) visit (ie, at least 48 hours after end of treatment \[day 10\]) and no recurrence within 56 days \[day 66\] or within 84 days \[day 94\]. Recurrence was defined as a new episode of diarrhea (3 or more UBMs in a 24-hour period) with a positive toxin result, using a Sponsor-approved C. difficile free toxin test and, in the opinion of the Investigator, requiring retreatment with an antibacterial agent for C. difficile.
Outcome measures
| Measure |
Segment 2A: Ibezapolstat (ACX-362E) Open-Label Single-Arm
n=6 Participants
Participants with diarrhea caused by C. difficile were treated with ibezapolstat 450 mg orally (3 x 150 mg capsules) every 12 hours for 10 days. Study drug was administered with 240 mL water. Participants were followed for recurrence for 28±2 days, regardless of response to ibezapolstat. Safety, tolerability, and efficacy were assessed by the Trial Oversight Committee which then recommended early termination of this segment of the trial and advancement to the 2B Segment because the first 10 patients demonstrated clinical cure.
|
Segment 2B: Vancomycin Arm--double-blind, Randomized, Active-controlled Clinical Segment
n=8 Participants
Participants with diarrhea caused by C. difficile who were randomized to this arm received vancomycin every 6 hours (1 capsule 125 mg + 2 placebo capsules every 12 hours or 1 capsule 125 mg every 12 hours). Participants were followed for 28±2 days for recurrence. Blinding was maintained by over-encapsulation.
|
|---|---|---|
|
Segment 2B Intent-to-Treat (ITT) Extension Population: Extended Clinical Cure (ECC) of Clostridioides Difficile Infection (CDI)
Extended Clinical Cure 56 days after End of Treatment (Day 66) · yes
|
5 Participants
|
7 Participants
|
|
Segment 2B Intent-to-Treat (ITT) Extension Population: Extended Clinical Cure (ECC) of Clostridioides Difficile Infection (CDI)
Extended Clinical Cure 56 days after End of Treatment (Day 66) · no
|
1 Participants
|
1 Participants
|
|
Segment 2B Intent-to-Treat (ITT) Extension Population: Extended Clinical Cure (ECC) of Clostridioides Difficile Infection (CDI)
Extended Clinical Cure 84 days after End of Treatment (Day 94) · yes
|
5 Participants
|
7 Participants
|
|
Segment 2B Intent-to-Treat (ITT) Extension Population: Extended Clinical Cure (ECC) of Clostridioides Difficile Infection (CDI)
Extended Clinical Cure 84 days after End of Treatment (Day 94) · no
|
1 Participants
|
1 Participants
|
Adverse Events
Segment 2A: Ibezapolstat (ACX-362E) Open-Label Single-Arm
Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths
Segment 2B: Ibezapolstat Arm--Double-blind, Randomized, Active-controlled Clinical Segment
Serious events: 1 serious events
Other events: 6 other events
Deaths: 0 deaths
Segment 2B: Vancomycin Arm--Double-blind, Randomized, Active-controlled Clinical Segment
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Segment 2A: Ibezapolstat (ACX-362E) Open-Label Single-Arm
n=10 participants at risk
Participants with diarrhea caused by C. difficile were treated with ibezapolstat 450 mg orally (3 x 150 mg capsules) every 12 hours for 10 days. Study drug was administered with 240 mL water. Participants were followed for recurrence for 28±2 days, regardless of response to ibezapolstat. Safety, tolerability, and efficacy were assessed by the Trial Oversight Committee which then recommended early termination of this segment of the trial and advancement to the 2B Segment because the first 10 patients demonstrated clinical cure.
|
Segment 2B: Ibezapolstat Arm--Double-blind, Randomized, Active-controlled Clinical Segment
n=17 participants at risk
Participants with diarrhea caused by C. difficile who were randomized to this arm received 450 mg ibezapolstat (3 x 150 mg capsules) every 12 hours for 10 days with placebo every 12 hours for 10 days (to maintain blind). Participants were followed for 28±2 days for recurrence. Blinding was maintained by over-encapsulation. 1 participant from the original population did not receive the study drug and was not included in calculations.
|
Segment 2B: Vancomycin Arm--Double-blind, Randomized, Active-controlled Clinical Segment
n=14 participants at risk
Participants with diarrhea caused by C. difficile who were randomized to this arm received vancomycin every 6 hours (1 capsule 125 mg + 2 placebo capsules every 12 hours or 1 capsule 125 mg every 12 hours). Participants were followed for 28±2 days for recurrence. Blinding was maintained by over-encapsulation.
|
|---|---|---|---|
|
Infections and infestations
Herpes zoster a
|
0.00%
0/10 • 40 days--from the time the participant gave informed consent through study completion
Participants were instructed to report AEs at each study visit. Study visits occurred on Days 1, 3, 5, 8, 10, 12, 20, 30, 38, and 40. No participants had AEs leading to study withdrawal or discontinuation.
|
5.9%
1/17 • Number of events 1 • 40 days--from the time the participant gave informed consent through study completion
Participants were instructed to report AEs at each study visit. Study visits occurred on Days 1, 3, 5, 8, 10, 12, 20, 30, 38, and 40. No participants had AEs leading to study withdrawal or discontinuation.
|
0.00%
0/14 • 40 days--from the time the participant gave informed consent through study completion
Participants were instructed to report AEs at each study visit. Study visits occurred on Days 1, 3, 5, 8, 10, 12, 20, 30, 38, and 40. No participants had AEs leading to study withdrawal or discontinuation.
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/10 • 40 days--from the time the participant gave informed consent through study completion
Participants were instructed to report AEs at each study visit. Study visits occurred on Days 1, 3, 5, 8, 10, 12, 20, 30, 38, and 40. No participants had AEs leading to study withdrawal or discontinuation.
|
5.9%
1/17 • Number of events 1 • 40 days--from the time the participant gave informed consent through study completion
Participants were instructed to report AEs at each study visit. Study visits occurred on Days 1, 3, 5, 8, 10, 12, 20, 30, 38, and 40. No participants had AEs leading to study withdrawal or discontinuation.
|
0.00%
0/14 • 40 days--from the time the participant gave informed consent through study completion
Participants were instructed to report AEs at each study visit. Study visits occurred on Days 1, 3, 5, 8, 10, 12, 20, 30, 38, and 40. No participants had AEs leading to study withdrawal or discontinuation.
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/10 • 40 days--from the time the participant gave informed consent through study completion
Participants were instructed to report AEs at each study visit. Study visits occurred on Days 1, 3, 5, 8, 10, 12, 20, 30, 38, and 40. No participants had AEs leading to study withdrawal or discontinuation.
|
5.9%
1/17 • Number of events 1 • 40 days--from the time the participant gave informed consent through study completion
Participants were instructed to report AEs at each study visit. Study visits occurred on Days 1, 3, 5, 8, 10, 12, 20, 30, 38, and 40. No participants had AEs leading to study withdrawal or discontinuation.
|
0.00%
0/14 • 40 days--from the time the participant gave informed consent through study completion
Participants were instructed to report AEs at each study visit. Study visits occurred on Days 1, 3, 5, 8, 10, 12, 20, 30, 38, and 40. No participants had AEs leading to study withdrawal or discontinuation.
|
Other adverse events
| Measure |
Segment 2A: Ibezapolstat (ACX-362E) Open-Label Single-Arm
n=10 participants at risk
Participants with diarrhea caused by C. difficile were treated with ibezapolstat 450 mg orally (3 x 150 mg capsules) every 12 hours for 10 days. Study drug was administered with 240 mL water. Participants were followed for recurrence for 28±2 days, regardless of response to ibezapolstat. Safety, tolerability, and efficacy were assessed by the Trial Oversight Committee which then recommended early termination of this segment of the trial and advancement to the 2B Segment because the first 10 patients demonstrated clinical cure.
|
Segment 2B: Ibezapolstat Arm--Double-blind, Randomized, Active-controlled Clinical Segment
n=17 participants at risk
Participants with diarrhea caused by C. difficile who were randomized to this arm received 450 mg ibezapolstat (3 x 150 mg capsules) every 12 hours for 10 days with placebo every 12 hours for 10 days (to maintain blind). Participants were followed for 28±2 days for recurrence. Blinding was maintained by over-encapsulation. 1 participant from the original population did not receive the study drug and was not included in calculations.
|
Segment 2B: Vancomycin Arm--Double-blind, Randomized, Active-controlled Clinical Segment
n=14 participants at risk
Participants with diarrhea caused by C. difficile who were randomized to this arm received vancomycin every 6 hours (1 capsule 125 mg + 2 placebo capsules every 12 hours or 1 capsule 125 mg every 12 hours). Participants were followed for 28±2 days for recurrence. Blinding was maintained by over-encapsulation.
|
|---|---|---|---|
|
Infections and infestations
COVID-19
|
0.00%
0/10 • 40 days--from the time the participant gave informed consent through study completion
Participants were instructed to report AEs at each study visit. Study visits occurred on Days 1, 3, 5, 8, 10, 12, 20, 30, 38, and 40. No participants had AEs leading to study withdrawal or discontinuation.
|
5.9%
1/17 • Number of events 1 • 40 days--from the time the participant gave informed consent through study completion
Participants were instructed to report AEs at each study visit. Study visits occurred on Days 1, 3, 5, 8, 10, 12, 20, 30, 38, and 40. No participants had AEs leading to study withdrawal or discontinuation.
|
0.00%
0/14 • 40 days--from the time the participant gave informed consent through study completion
Participants were instructed to report AEs at each study visit. Study visits occurred on Days 1, 3, 5, 8, 10, 12, 20, 30, 38, and 40. No participants had AEs leading to study withdrawal or discontinuation.
|
|
Gastrointestinal disorders
Nausea
|
20.0%
2/10 • Number of events 2 • 40 days--from the time the participant gave informed consent through study completion
Participants were instructed to report AEs at each study visit. Study visits occurred on Days 1, 3, 5, 8, 10, 12, 20, 30, 38, and 40. No participants had AEs leading to study withdrawal or discontinuation.
|
11.8%
2/17 • Number of events 2 • 40 days--from the time the participant gave informed consent through study completion
Participants were instructed to report AEs at each study visit. Study visits occurred on Days 1, 3, 5, 8, 10, 12, 20, 30, 38, and 40. No participants had AEs leading to study withdrawal or discontinuation.
|
0.00%
0/14 • 40 days--from the time the participant gave informed consent through study completion
Participants were instructed to report AEs at each study visit. Study visits occurred on Days 1, 3, 5, 8, 10, 12, 20, 30, 38, and 40. No participants had AEs leading to study withdrawal or discontinuation.
|
|
Gastrointestinal disorders
Vomiting
|
10.0%
1/10 • Number of events 1 • 40 days--from the time the participant gave informed consent through study completion
Participants were instructed to report AEs at each study visit. Study visits occurred on Days 1, 3, 5, 8, 10, 12, 20, 30, 38, and 40. No participants had AEs leading to study withdrawal or discontinuation.
|
0.00%
0/17 • 40 days--from the time the participant gave informed consent through study completion
Participants were instructed to report AEs at each study visit. Study visits occurred on Days 1, 3, 5, 8, 10, 12, 20, 30, 38, and 40. No participants had AEs leading to study withdrawal or discontinuation.
|
0.00%
0/14 • 40 days--from the time the participant gave informed consent through study completion
Participants were instructed to report AEs at each study visit. Study visits occurred on Days 1, 3, 5, 8, 10, 12, 20, 30, 38, and 40. No participants had AEs leading to study withdrawal or discontinuation.
|
|
Gastrointestinal disorders
Gastrooesophageal reflux disease
|
0.00%
0/10 • 40 days--from the time the participant gave informed consent through study completion
Participants were instructed to report AEs at each study visit. Study visits occurred on Days 1, 3, 5, 8, 10, 12, 20, 30, 38, and 40. No participants had AEs leading to study withdrawal or discontinuation.
|
11.8%
2/17 • Number of events 2 • 40 days--from the time the participant gave informed consent through study completion
Participants were instructed to report AEs at each study visit. Study visits occurred on Days 1, 3, 5, 8, 10, 12, 20, 30, 38, and 40. No participants had AEs leading to study withdrawal or discontinuation.
|
0.00%
0/14 • 40 days--from the time the participant gave informed consent through study completion
Participants were instructed to report AEs at each study visit. Study visits occurred on Days 1, 3, 5, 8, 10, 12, 20, 30, 38, and 40. No participants had AEs leading to study withdrawal or discontinuation.
|
|
Gastrointestinal disorders
Abdominal distension
|
0.00%
0/10 • 40 days--from the time the participant gave informed consent through study completion
Participants were instructed to report AEs at each study visit. Study visits occurred on Days 1, 3, 5, 8, 10, 12, 20, 30, 38, and 40. No participants had AEs leading to study withdrawal or discontinuation.
|
0.00%
0/17 • 40 days--from the time the participant gave informed consent through study completion
Participants were instructed to report AEs at each study visit. Study visits occurred on Days 1, 3, 5, 8, 10, 12, 20, 30, 38, and 40. No participants had AEs leading to study withdrawal or discontinuation.
|
7.1%
1/14 • Number of events 1 • 40 days--from the time the participant gave informed consent through study completion
Participants were instructed to report AEs at each study visit. Study visits occurred on Days 1, 3, 5, 8, 10, 12, 20, 30, 38, and 40. No participants had AEs leading to study withdrawal or discontinuation.
|
|
Infections and infestations
Skin candida
|
10.0%
1/10 • Number of events 1 • 40 days--from the time the participant gave informed consent through study completion
Participants were instructed to report AEs at each study visit. Study visits occurred on Days 1, 3, 5, 8, 10, 12, 20, 30, 38, and 40. No participants had AEs leading to study withdrawal or discontinuation.
|
0.00%
0/17 • 40 days--from the time the participant gave informed consent through study completion
Participants were instructed to report AEs at each study visit. Study visits occurred on Days 1, 3, 5, 8, 10, 12, 20, 30, 38, and 40. No participants had AEs leading to study withdrawal or discontinuation.
|
0.00%
0/14 • 40 days--from the time the participant gave informed consent through study completion
Participants were instructed to report AEs at each study visit. Study visits occurred on Days 1, 3, 5, 8, 10, 12, 20, 30, 38, and 40. No participants had AEs leading to study withdrawal or discontinuation.
|
|
Infections and infestations
Nasopharyngitis
|
0.00%
0/10 • 40 days--from the time the participant gave informed consent through study completion
Participants were instructed to report AEs at each study visit. Study visits occurred on Days 1, 3, 5, 8, 10, 12, 20, 30, 38, and 40. No participants had AEs leading to study withdrawal or discontinuation.
|
0.00%
0/17 • 40 days--from the time the participant gave informed consent through study completion
Participants were instructed to report AEs at each study visit. Study visits occurred on Days 1, 3, 5, 8, 10, 12, 20, 30, 38, and 40. No participants had AEs leading to study withdrawal or discontinuation.
|
7.1%
1/14 • Number of events 1 • 40 days--from the time the participant gave informed consent through study completion
Participants were instructed to report AEs at each study visit. Study visits occurred on Days 1, 3, 5, 8, 10, 12, 20, 30, 38, and 40. No participants had AEs leading to study withdrawal or discontinuation.
|
|
Infections and infestations
Tooth infection
|
0.00%
0/10 • 40 days--from the time the participant gave informed consent through study completion
Participants were instructed to report AEs at each study visit. Study visits occurred on Days 1, 3, 5, 8, 10, 12, 20, 30, 38, and 40. No participants had AEs leading to study withdrawal or discontinuation.
|
0.00%
0/17 • 40 days--from the time the participant gave informed consent through study completion
Participants were instructed to report AEs at each study visit. Study visits occurred on Days 1, 3, 5, 8, 10, 12, 20, 30, 38, and 40. No participants had AEs leading to study withdrawal or discontinuation.
|
7.1%
1/14 • Number of events 1 • 40 days--from the time the participant gave informed consent through study completion
Participants were instructed to report AEs at each study visit. Study visits occurred on Days 1, 3, 5, 8, 10, 12, 20, 30, 38, and 40. No participants had AEs leading to study withdrawal or discontinuation.
|
|
Nervous system disorders
Headache
|
20.0%
2/10 • Number of events 2 • 40 days--from the time the participant gave informed consent through study completion
Participants were instructed to report AEs at each study visit. Study visits occurred on Days 1, 3, 5, 8, 10, 12, 20, 30, 38, and 40. No participants had AEs leading to study withdrawal or discontinuation.
|
0.00%
0/17 • 40 days--from the time the participant gave informed consent through study completion
Participants were instructed to report AEs at each study visit. Study visits occurred on Days 1, 3, 5, 8, 10, 12, 20, 30, 38, and 40. No participants had AEs leading to study withdrawal or discontinuation.
|
7.1%
1/14 • Number of events 1 • 40 days--from the time the participant gave informed consent through study completion
Participants were instructed to report AEs at each study visit. Study visits occurred on Days 1, 3, 5, 8, 10, 12, 20, 30, 38, and 40. No participants had AEs leading to study withdrawal or discontinuation.
|
|
Nervous system disorders
Migraine
|
10.0%
1/10 • Number of events 1 • 40 days--from the time the participant gave informed consent through study completion
Participants were instructed to report AEs at each study visit. Study visits occurred on Days 1, 3, 5, 8, 10, 12, 20, 30, 38, and 40. No participants had AEs leading to study withdrawal or discontinuation.
|
0.00%
0/17 • 40 days--from the time the participant gave informed consent through study completion
Participants were instructed to report AEs at each study visit. Study visits occurred on Days 1, 3, 5, 8, 10, 12, 20, 30, 38, and 40. No participants had AEs leading to study withdrawal or discontinuation.
|
0.00%
0/14 • 40 days--from the time the participant gave informed consent through study completion
Participants were instructed to report AEs at each study visit. Study visits occurred on Days 1, 3, 5, 8, 10, 12, 20, 30, 38, and 40. No participants had AEs leading to study withdrawal or discontinuation.
|
|
Metabolism and nutrition disorders
Gout
|
0.00%
0/10 • 40 days--from the time the participant gave informed consent through study completion
Participants were instructed to report AEs at each study visit. Study visits occurred on Days 1, 3, 5, 8, 10, 12, 20, 30, 38, and 40. No participants had AEs leading to study withdrawal or discontinuation.
|
5.9%
1/17 • Number of events 2 • 40 days--from the time the participant gave informed consent through study completion
Participants were instructed to report AEs at each study visit. Study visits occurred on Days 1, 3, 5, 8, 10, 12, 20, 30, 38, and 40. No participants had AEs leading to study withdrawal or discontinuation.
|
0.00%
0/14 • 40 days--from the time the participant gave informed consent through study completion
Participants were instructed to report AEs at each study visit. Study visits occurred on Days 1, 3, 5, 8, 10, 12, 20, 30, 38, and 40. No participants had AEs leading to study withdrawal or discontinuation.
|
|
Vascular disorders
Hot flush
|
0.00%
0/10 • 40 days--from the time the participant gave informed consent through study completion
Participants were instructed to report AEs at each study visit. Study visits occurred on Days 1, 3, 5, 8, 10, 12, 20, 30, 38, and 40. No participants had AEs leading to study withdrawal or discontinuation.
|
5.9%
1/17 • Number of events 1 • 40 days--from the time the participant gave informed consent through study completion
Participants were instructed to report AEs at each study visit. Study visits occurred on Days 1, 3, 5, 8, 10, 12, 20, 30, 38, and 40. No participants had AEs leading to study withdrawal or discontinuation.
|
0.00%
0/14 • 40 days--from the time the participant gave informed consent through study completion
Participants were instructed to report AEs at each study visit. Study visits occurred on Days 1, 3, 5, 8, 10, 12, 20, 30, 38, and 40. No participants had AEs leading to study withdrawal or discontinuation.
|
|
Investigations
Blood potassium decreased
|
0.00%
0/10 • 40 days--from the time the participant gave informed consent through study completion
Participants were instructed to report AEs at each study visit. Study visits occurred on Days 1, 3, 5, 8, 10, 12, 20, 30, 38, and 40. No participants had AEs leading to study withdrawal or discontinuation.
|
0.00%
0/17 • 40 days--from the time the participant gave informed consent through study completion
Participants were instructed to report AEs at each study visit. Study visits occurred on Days 1, 3, 5, 8, 10, 12, 20, 30, 38, and 40. No participants had AEs leading to study withdrawal or discontinuation.
|
7.1%
1/14 • Number of events 1 • 40 days--from the time the participant gave informed consent through study completion
Participants were instructed to report AEs at each study visit. Study visits occurred on Days 1, 3, 5, 8, 10, 12, 20, 30, 38, and 40. No participants had AEs leading to study withdrawal or discontinuation.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee The sponsor is responsible for the conduct of the study, data analyses, and all results. All data are proprietary and belong to the sponsor, not to the investigator.
- Publication restrictions are in place
Restriction type: OTHER