Cholera
Conditions
Brief summary
This trial was designed to assess safety and preliminary efficacy of oral doses of iOWH032 on diarrhea output and clinical symptoms after a cholera challenge in healthy adult participants.
Detailed description
The study consists of a screening phase, an inpatient containment period with challenge with Vibrio cholerae on Day 1 followed by treatment with iOWH032 or placebo and a post-challenge observation period until discharge, an outpatient follow-up period of at least 28 days, and a final follow-up (by telephone) 6 months post-challenge (Day 180) for the collection of serious adverse events. Participants will be randomized 1:1 to receive either iOWH032 500 mg every 8 hours for three days or matching placebo. Blinded therapeutic dosing will start at the onset of diarrhea or by 48 hours after ingesting the challenge inoculum of V. cholerae. The observation and management of cholera diarrhea and symptomatology will occur on an inpatient isolation research ward over a duration of approximately 11 days, including a three-day course of antibiotics to treat all participants prior to discharge from the inpatient unit.
Interventions
DRUGiOWH032
Anti-secretory synthetically manufactured small molecule designed to inhibit the cystic fibrosis transmembrane conductance regulator chloride channel.
DRUGPlacebo
Oral tablets matching iOWH032 on taste, appearance, dissolution time with the same excipients but no active ingredients.
OTHERV. cholerae Challenge
Freshly-harvested, wild-type Vibrio (V.) cholerae El Tor Inaba strain N16961,10\^6 cfu suspended in 30 mL of sodium bicarbonate solution ingested orally.
DRUGAntibiotics
Antibiotic therapy may include: * Ciprofloxacin 500 mg, twice daily; * Azithromycin 500 mg, once daily (for those persons who are allergic to fluoroquinolones); * Doxycycline 300 mg, once daily (for those persons who are allergic to fluoroquinolones)
Sponsors
University of Maryland, Baltimore
Pharmaron
PATH
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 44 Years
Healthy volunteers
Yes
Inclusion criteria
1. Willing and able to understand and provide written informed consent 2. Healthy male and female adults, age 18 to 44 years (inclusive), without clinically significant medical history, physical or clinical laboratory abnormalities (as per protocol-defined acceptable ranges), and protocol-defined abnormal electrocardiogram results at screening 3. All women must have a negative serum pregnancy test at screening and one day prior to challenge. 4. Agreement by participants to use an adequate method of contraception\* during the study and for 4 weeks before and after the challenge. 5. Able to pass a written examination (comprehension assessment test) with a score of ≥ 70%, in order to demonstrate their comprehension of this study. If a participant scores at least 50%, then they will be given one more opportunity to re-test after further re-education. 6. Willing and able to comply with the study requirements and procedures. * Adequate contraception is defined as a contraceptive method with failure rate of less than 1% per year when used consistently and correctly and when applicable, in accordance with the product label; includes, but is not limited to, barrier with additional spermicidal foam or jelly, intrauterine device, hormonal contraception (started at least 4 weeks prior to study enrollment), or women who have intercourse limited to men who underwent vasectomy.
Exclusion criteria
1. Clinically significant history of immunodeficiency, cardiovascular disease, respiratory disease, endocrine disorder, liver disease, renal disease, gastrointestinal disease, anal or rectal disorders, neurologic disease, 2. Current nicotine use or drug, alcohol abuse within the past 6 months 3. Recipient of bone marrow or solid organ transplant 4. Use of systemic chemotherapy in the past 5 years 5. Has a malignancy (excluding localized non-melanoma skin cancers) or lymphoproliferative disorders diagnosed or treated within the past 5 years 6. Received or plans to receive systemic immunosuppressive therapy, radiation therapy, parenteral or high-dosage inhaled steroids (\> 800 µg/day of beclomethasone dipropionate or equivalent) within 6 months prior to the enrollment through 28 days after challenge 7. Have a history of hospitalization for psychiatric illness, suicide attempt, or confinement for danger to self or others, within the past 10 years. Participants with a psychiatric disorder (not meeting
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Diarrheal Stool Output Rate | Day 1 - Day 5 (up to first dose of antibiotic therapy) | Diarrheal stool output rate is defined as the total volume of diarrheal stools (in mL, Grade 3 and above) divided by the number of hours between initiation of study drug (iOWH032 or placebo) and initiation of antibiotic therapy. Stools were graded based on consistency as follows: * Grade 1 - well formed (normal stool, does not take the shape of the container) * Grade 2 - soft (normal stool, does not take the shape of the container) * Grade 3 - thick liquid (diarrhea, takes the shape of the container readily) * Grade 4 - opaque watery diarrhea * Grade 5 - rice water diarrhea (clear watery) The definition of diarrhea is a grade 3 or higher stool. |
| Diarrheal Stool Output Rate Including Participants With Symptom Onset After 48 Hours | Day 1 - Day 5 (up to first dose of antibiotic therapy) | Stools were graded based on consistency as follows: * Grade 1 - well formed (normal stool, does not take the shape of the container) * Grade 2 - soft (normal stool, does not take the shape of the container) * Grade 3 - thick liquid (diarrhea, takes the shape of the container readily) * Grade 4 - opaque watery diarrhea * Grade 5 - rice water diarrhea (clear watery) The definition of diarrhea is a grade 3 or higher stool. For participants with symptom onset within 48 hours of challenge diarrheal stool output rate is defined as the total volume of diarrheal stools (mL, Grade 3 and above) divided by the number of hours between initiation of study product dosing and initiation of antibiotic therapy. For participants with symptom onset after 48 hours diarrheal stool output rate is defined as the total volume of diarrheal stools (mL, Grade 3 and above) divided by the number of hours between onset of symptoms and initiation of antibiotic therapy. |
| Number of Participants With Treatment-emergent Serious Adverse Events | Day 1 - Day 180 | A serious adverse event (SAE) is any adverse event that resulted in any of the following outcomes: 1. Death 2. A life-threatening event. 3. Required inpatient hospitalization or prolongation of existing hospitalization 4. Resulted in persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions 5. Congenital abnormality or birth defect 6. Important medical event that may not result in one of the above outcomes but may jeopardize the health of the study participant and/or requires medical or surgical intervention to prevent one of the outcomes listed in the above definition of serious adverse event. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Peak Shedding of Cholera Organisms | Day 1 to Day 5 (prior to first dose of antibiotic) | Quantitative cultures were performed on the first two stool samples of each 24-hour period prior to the initiation of antibiotics to determine the number of cholera organisms per gram of stool. Peak shedding represents the highest colony-forming unit (CFU) counts observed for each participant. |
| Duration of Diarrheal Episodes | Day 1 to Day 5 (prior to first dose of antibiotics) | Duration of diarrheal episodes was calculated using Kaplan-Meier methods as the time from cholera challenge to the time of the first formed stool (Grade 1), after which all following stools were also formed. |
| Total Number of Loose (Grade 3-5) Stools | Day 1 to Day 5 (prior to first dose of antibiotic therapy) | Total number of loose stools (Grade 3 and above) per participant during the interval immediately following challenge and prior to initiation of antibiotic therapy. |
| Percentage of Participants With Moderate to Severe Diarrhea With Onset Within 48 Hours Following Cholera Challenge | Day 1 - Day 5 (up to first dose of antibiotic therapy) | The percentage of participants with moderate to severe diarrhea with onset within 48 hours following cholera challenge. Diarrhea was defined as a grade 3 or higher stool based on the following scale: * Grade 1 - well formed (normal stool, does not take the shape of the container) * Grade 2 - soft (normal stool, does not take the shape of the container) * Grade 3 - thick liquid (diarrhea, takes the shape of the container readily) * Grade 4 - opaque watery diarrhea * Grade 5 - rice water diarrhea (clear watery) Diarrheal stools (Grade 3-5) were graded for severity according to the following: Mild: ≤ 3 liters loose stools; Moderate: \> 3 liters loose stools; Severe: \> 5 liters loose stools. |
| Percentage of Participants With Vomiting Following Cholera Challenge | Day 1 to Day 5, prior to first dose of antibiotics | — |
| Number of Participants With Solicited Adverse Effects | Day 1 - Day 8 | Solicited adverse events (AEs) include nausea, abdominal discomfort and pain, abdominal cramps, headache, malaise, anorexia, pollakiuria, micturition urgency, sinus tachycardia, increased alertness, and were collected by interview through 7 days post-challenge (Days 1-8) |
| Number of Participants With Unsolicited Treatment-emergent Adverse Events (TEAE) | From first dose of study drug up to Day 29 | Unsolicited AEs include any AEs reported spontaneously by the participant, observed by the study personnel during study visits or those identified during review of medical records or source documents. Investigators assigned causality of unsolicited AEs to either the study drug, cholera infection, or an alternate etiology. |
| Percentage of Participants With Fever Following Cholera Challenge | Day 1 to Day 5, prior to first dose of antibiotics | The presence of fever was defined as a body temperature of ≥ 39°C (102.1°F). |
| Attack Rate of Any Diarrhea Following Cholera Challenge | Day 1 - Day 5 (up to first dose of antibiotic therapy) | Attack rate of any diarrhea following cholera challenge is defined as the number of participants with 2 or more loose stools (Grade 3-5) totaling \> 200 mL or 1 loose (Grade 3-5) stool \> 300 mL, respectively, with onset within 48 hours of cholera challenge. |
| Area Under the Curve (AUC) of Diarrheal Stool Volume Between Challenge Dose and Initiation of Antibiotics | Day 1 to Day 5 (prior to first dose of antibiotic) | The AUC of diarrheal stool volume and cholera organisms was computed via the trapezoidal rule. |
Countries
United States
Participant flow
Recruitment details
A total of 47 healthy adults were enrolled at one clinical research site in the United States. Participants were confined in an inpatient isolation research ward for a duration of approximately 11 days until discharge criteria were met.
Pre-assignment details
Participants were randomized in a 1:1 ratio stratified by blood type status (O vs. Non-O) to receive either iOWH032 500 mg every 8 hours for three days or matching placebo.
Participants by arm
| Arm | Count |
|---|---|
| iOWH032 On Day 1, participants were challenged with 10\^6 CFU of freshly-harvested wild-type V. cholerae. At the onset of diarrhea, or at 48 hours after challenge, whichever was first, participants received oral iOWH032 500 mg tablets every 8 hours for 3 days. Participants received a 3-day course of antibiotics starting 4 days post-challenge, or sooner if the participant met the criterion for severe cholera diarrhea. | 23 |
| Placebo On Day 1, participants were challenged with 10\^6 CFU of freshly-harvested wild-type V. cholerae. At the onset of diarrhea, or at 48 hours after challenge, whichever was first, participants received oral matching iOWH032 placebo tablets every 8 hours for 3 days. Participants received a 3-day course of antibiotics starting 4 days post-challenge, or sooner if the participant met the criterion for severe cholera diarrhea. | 24 |
| Total | 47 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 0 | 2 |
Baseline characteristics
| Characteristic | iOWH032 | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 32.0 years STANDARD_DEVIATION 6.15 | 32.3 years STANDARD_DEVIATION 5.97 | 32.1 years STANDARD_DEVIATION 6 |
| Blood Type Non-O | 11 Participants | 11 Participants | 22 Participants |
| Blood Type Type O | 12 Participants | 13 Participants | 25 Participants |
| Race/Ethnicity, Customized Black or African American | 21 Participants | 19 Participants | 40 Participants |
| Race/Ethnicity, Customized White | 2 Participants | 5 Participants | 7 Participants |
| Sex: Female, Male Female | 9 Participants | 11 Participants | 20 Participants |
| Sex: Female, Male Male | 14 Participants | 13 Participants | 27 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 23 | 0 / 24 |
| other Total, other adverse events | 18 / 23 | 21 / 24 |
| serious Total, serious adverse events | 0 / 23 | 1 / 24 |
Outcome results
Primary
Diarrheal Stool Output Rate
Diarrheal stool output rate is defined as the total volume of diarrheal stools (in mL, Grade 3 and above) divided by the number of hours between initiation of study drug (iOWH032 or placebo) and initiation of antibiotic therapy. Stools were graded based on consistency as follows: * Grade 1 - well formed (normal stool, does not take the shape of the container) * Grade 2 - soft (normal stool, does not take the shape of the container) * Grade 3 - thick liquid (diarrhea, takes the shape of the container readily) * Grade 4 - opaque watery diarrhea * Grade 5 - rice water diarrhea (clear watery) The definition of diarrhea is a grade 3 or higher stool.
Time frame: Day 1 - Day 5 (up to first dose of antibiotic therapy)
Population: Randomized participants who received at least one dose of study drug (iOWH032 or placebo) and with indication of cholera infection (diarrheal stool output of Grade 3 or higher) within 48 hours of challenge.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| iOWH032 | Diarrheal Stool Output Rate | 25.42 mL/hour |
| Placebo | Diarrheal Stool Output Rate | 32.57 mL/hour |
p-value: 0.225495% CI: [-30.9, 28.6]Van Elteren test
Primary
Diarrheal Stool Output Rate Including Participants With Symptom Onset After 48 Hours
Stools were graded based on consistency as follows: * Grade 1 - well formed (normal stool, does not take the shape of the container) * Grade 2 - soft (normal stool, does not take the shape of the container) * Grade 3 - thick liquid (diarrhea, takes the shape of the container readily) * Grade 4 - opaque watery diarrhea * Grade 5 - rice water diarrhea (clear watery) The definition of diarrhea is a grade 3 or higher stool. For participants with symptom onset within 48 hours of challenge diarrheal stool output rate is defined as the total volume of diarrheal stools (mL, Grade 3 and above) divided by the number of hours between initiation of study product dosing and initiation of antibiotic therapy. For participants with symptom onset after 48 hours diarrheal stool output rate is defined as the total volume of diarrheal stools (mL, Grade 3 and above) divided by the number of hours between onset of symptoms and initiation of antibiotic therapy.
Time frame: Day 1 - Day 5 (up to first dose of antibiotic therapy)
Population: Randomized participants who received at least one dose of study drug (iOWH032 or placebo) and with indication of cholera infection (diarrheal stool output of Grade 3 or higher) after challenge.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| iOWH032 | Diarrheal Stool Output Rate Including Participants With Symptom Onset After 48 Hours | 25.42 mL/hour |
| Placebo | Diarrheal Stool Output Rate Including Participants With Symptom Onset After 48 Hours | 29.22 mL/hour |
p-value: 0.275195% CI: [-26.3, 27.4]Van Elteren test
Primary
Number of Participants With Treatment-emergent Serious Adverse Events
A serious adverse event (SAE) is any adverse event that resulted in any of the following outcomes: 1. Death 2. A life-threatening event. 3. Required inpatient hospitalization or prolongation of existing hospitalization 4. Resulted in persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions 5. Congenital abnormality or birth defect 6. Important medical event that may not result in one of the above outcomes but may jeopardize the health of the study participant and/or requires medical or surgical intervention to prevent one of the outcomes listed in the above definition of serious adverse event.
Time frame: Day 1 - Day 180
Population: All participants who received any study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| iOWH032 | Number of Participants With Treatment-emergent Serious Adverse Events | 0 Participants |
| Placebo | Number of Participants With Treatment-emergent Serious Adverse Events | 1 Participants |
Secondary
Area Under the Curve (AUC) of Diarrheal Stool Volume Between Challenge Dose and Initiation of Antibiotics
The AUC of diarrheal stool volume and cholera organisms was computed via the trapezoidal rule.
Time frame: Day 1 to Day 5 (prior to first dose of antibiotic)
Population: Randomized participants who received at least one dose of study drug (iOWH032 or placebo) and with indication of cholera infection (diarrheal stool output of Grade 3 or higher) within 48 hours of challenge.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| iOWH032 | Area Under the Curve (AUC) of Diarrheal Stool Volume Between Challenge Dose and Initiation of Antibiotics | 14.91 liters * hours |
| Placebo | Area Under the Curve (AUC) of Diarrheal Stool Volume Between Challenge Dose and Initiation of Antibiotics | 13.80 liters * hours |
p-value: 0.599295% CI: [-4.5, 7.8]Van Elteren test
Secondary
Attack Rate of Any Diarrhea Following Cholera Challenge
Attack rate of any diarrhea following cholera challenge is defined as the number of participants with 2 or more loose stools (Grade 3-5) totaling \> 200 mL or 1 loose (Grade 3-5) stool \> 300 mL, respectively, with onset within 48 hours of cholera challenge.
Time frame: Day 1 - Day 5 (up to first dose of antibiotic therapy)
Population: Randomized participants who received at least one dose of study drug (iOWH032 or placebo) and with indication of cholera infection (diarrheal stool output of Grade 3 or higher) within 48 hours of challenge.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| iOWH032 | Attack Rate of Any Diarrhea Following Cholera Challenge | 93.8 percentage of participants |
| Placebo | Attack Rate of Any Diarrhea Following Cholera Challenge | 100.0 percentage of participants |
p-value: 0.263695% CI: [-18.1, 5.6]Cochran-Mantel-Haenszel
Secondary
Duration of Diarrheal Episodes
Duration of diarrheal episodes was calculated using Kaplan-Meier methods as the time from cholera challenge to the time of the first formed stool (Grade 1), after which all following stools were also formed.
Time frame: Day 1 to Day 5 (prior to first dose of antibiotics)
Population: Randomized participants who received at least one dose of study drug (iOWH032 or placebo) and with indication of cholera infection (diarrheal stool output of Grade 3 or higher) within 48 hours of challenge.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| iOWH032 | Duration of Diarrheal Episodes | 156.48 hours |
| Placebo | Duration of Diarrheal Episodes | 169.68 hours |
p-value: 0.6527Log Rank
Secondary
Number of Participants With Solicited Adverse Effects
Solicited adverse events (AEs) include nausea, abdominal discomfort and pain, abdominal cramps, headache, malaise, anorexia, pollakiuria, micturition urgency, sinus tachycardia, increased alertness, and were collected by interview through 7 days post-challenge (Days 1-8)
Time frame: Day 1 - Day 8
Population: All participants who received any study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| iOWH032 | Number of Participants With Solicited Adverse Effects | Abdominal discomfort | 2 Participants |
| iOWH032 | Number of Participants With Solicited Adverse Effects | Malaise | 0 Participants |
| iOWH032 | Number of Participants With Solicited Adverse Effects | Headache | 1 Participants |
| iOWH032 | Number of Participants With Solicited Adverse Effects | Nausea | 0 Participants |
| iOWH032 | Number of Participants With Solicited Adverse Effects | Any solicited adverse event | 3 Participants |
| Placebo | Number of Participants With Solicited Adverse Effects | Nausea | 1 Participants |
| Placebo | Number of Participants With Solicited Adverse Effects | Any solicited adverse event | 2 Participants |
| Placebo | Number of Participants With Solicited Adverse Effects | Abdominal discomfort | 0 Participants |
| Placebo | Number of Participants With Solicited Adverse Effects | Headache | 0 Participants |
| Placebo | Number of Participants With Solicited Adverse Effects | Malaise | 1 Participants |
Secondary
Number of Participants With Unsolicited Treatment-emergent Adverse Events (TEAE)
Unsolicited AEs include any AEs reported spontaneously by the participant, observed by the study personnel during study visits or those identified during review of medical records or source documents. Investigators assigned causality of unsolicited AEs to either the study drug, cholera infection, or an alternate etiology.
Time frame: From first dose of study drug up to Day 29
Population: All participants who received any study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| iOWH032 | Number of Participants With Unsolicited Treatment-emergent Adverse Events (TEAE) | Any unsolicited TEAE | 18 Participants |
| iOWH032 | Number of Participants With Unsolicited Treatment-emergent Adverse Events (TEAE) | Study drug-related TEAE | 4 Participants |
| iOWH032 | Number of Participants With Unsolicited Treatment-emergent Adverse Events (TEAE) | TEAE leading to discontinuation from study | 0 Participants |
| iOWH032 | Number of Participants With Unsolicited Treatment-emergent Adverse Events (TEAE) | TEAE leading to death | 0 Participants |
| Placebo | Number of Participants With Unsolicited Treatment-emergent Adverse Events (TEAE) | TEAE leading to death | 0 Participants |
| Placebo | Number of Participants With Unsolicited Treatment-emergent Adverse Events (TEAE) | Any unsolicited TEAE | 21 Participants |
| Placebo | Number of Participants With Unsolicited Treatment-emergent Adverse Events (TEAE) | TEAE leading to discontinuation from study | 0 Participants |
| Placebo | Number of Participants With Unsolicited Treatment-emergent Adverse Events (TEAE) | Study drug-related TEAE | 3 Participants |
Secondary
Peak Shedding of Cholera Organisms
Quantitative cultures were performed on the first two stool samples of each 24-hour period prior to the initiation of antibiotics to determine the number of cholera organisms per gram of stool. Peak shedding represents the highest colony-forming unit (CFU) counts observed for each participant.
Time frame: Day 1 to Day 5 (prior to first dose of antibiotic)
Population: Randomized participants who received at least one dose of study drug (iOWH032 or placebo) and with indication of cholera infection (diarrheal stool output of Grade 3 or higher) within 48 hours of challenge.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| iOWH032 | Peak Shedding of Cholera Organisms | 124960186.25 CFU/g | Standard Deviation 163145761.682 |
| Placebo | Peak Shedding of Cholera Organisms | 186793500.00 CFU/g | Standard Deviation 304578375.607 |
Secondary
Percentage of Participants With Fever Following Cholera Challenge
The presence of fever was defined as a body temperature of ≥ 39°C (102.1°F).
Time frame: Day 1 to Day 5, prior to first dose of antibiotics
Population: Randomized participants who received at least one dose of study drug (iOWH032 or placebo) and with indication of cholera infection (diarrheal stool output of Grade 3 or higher) within 48 hours of challenge.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| iOWH032 | Percentage of Participants With Fever Following Cholera Challenge | 6.3 percentage of participants |
| Placebo | Percentage of Participants With Fever Following Cholera Challenge | 5.0 percentage of participants |
p-value: 0.870595% CI: [-14, 16.5]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants With Moderate to Severe Diarrhea With Onset Within 48 Hours Following Cholera Challenge
The percentage of participants with moderate to severe diarrhea with onset within 48 hours following cholera challenge. Diarrhea was defined as a grade 3 or higher stool based on the following scale: * Grade 1 - well formed (normal stool, does not take the shape of the container) * Grade 2 - soft (normal stool, does not take the shape of the container) * Grade 3 - thick liquid (diarrhea, takes the shape of the container readily) * Grade 4 - opaque watery diarrhea * Grade 5 - rice water diarrhea (clear watery) Diarrheal stools (Grade 3-5) were graded for severity according to the following: Mild: ≤ 3 liters loose stools; Moderate: \> 3 liters loose stools; Severe: \> 5 liters loose stools.
Time frame: Day 1 - Day 5 (up to first dose of antibiotic therapy)
Population: Randomized participants who received at least one dose of study drug (iOWH032 or placebo) and with indication of cholera infection (diarrheal stool output of Grade 3 or higher) within 48 hours of challenge.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| iOWH032 | Percentage of Participants With Moderate to Severe Diarrhea With Onset Within 48 Hours Following Cholera Challenge | 43.8 percentage of participants |
| Placebo | Percentage of Participants With Moderate to Severe Diarrhea With Onset Within 48 Hours Following Cholera Challenge | 55.0 percentage of participants |
p-value: 0.514595% CI: [-44.1, 21.6]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants With Vomiting Following Cholera Challenge
Time frame: Day 1 to Day 5, prior to first dose of antibiotics
Population: Randomized participants who received at least one dose of study drug (iOWH032 or placebo) and with indication of cholera infection (diarrheal stool output of Grade 3 or higher) within 48 hours of challenge.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| iOWH032 | Percentage of Participants With Vomiting Following Cholera Challenge | 6.3 percentage of participants |
| Placebo | Percentage of Participants With Vomiting Following Cholera Challenge | 25.0 percentage of participants |
p-value: 0.140495% CI: [-41.1, 3.6]Cochran-Mantel-Haenszel
Secondary
Total Number of Loose (Grade 3-5) Stools
Total number of loose stools (Grade 3 and above) per participant during the interval immediately following challenge and prior to initiation of antibiotic therapy.
Time frame: Day 1 to Day 5 (prior to first dose of antibiotic therapy)
Population: Randomized participants who received at least one dose of study drug (iOWH032 or placebo) and with indication of cholera infection (diarrheal stool output of Grade 3 or higher) within 48 hours of challenge.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| iOWH032 | Total Number of Loose (Grade 3-5) Stools | 12.0 loose stools |
| Placebo | Total Number of Loose (Grade 3-5) Stools | 10.5 loose stools |
p-value: 0.537795% CI: [-7, 5.5]Van Elteren test