CholeraPhase 2CASTNCT04150250
Cholera Anti-Secretory Treatment Trial
A Phase 2 study testing iOWH032, V. cholerae Challenge and Antibiotics in people with Cholera, run by PATH at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 44 yearsHealthy volunteers can take part
- Conditions the study is for
- Cholera
- What is being tested?
- iOWH032, V. cholerae Challenge and Antibiotics
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 47 participants
- Where
- 1 siteUnited States
- Study dates
- 4 Nov 2019to 27 Jul 2020
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 44 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Willing and able to understand and provide written informed consent
- 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
- All women must have a negative serum pregnancy test at screening and one day prior to challenge.
- Agreement by participants to use an adequate method of contraception* during the study and for 4 weeks before and after the challenge.
- 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.
- 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.
Who cannot join
- Clinically significant history of immunodeficiency, cardiovascular disease, respiratory disease, endocrine disorder, liver disease, renal disease, gastrointestinal disease, anal or rectal disorders, neurologic disease,
- Current nicotine use or drug, alcohol abuse within the past 6 months
- Recipient of bone marrow or solid organ transplant
- Use of systemic chemotherapy in the past 5 years
- Has a malignancy (excluding localized non-melanoma skin cancers) or lymphoproliferative disorders diagnosed or treated within the past 5 years
- 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
Show all 30Show fewer
- 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 exclusion criteria, e.g., attention-deficit hyperactivity disorder) that is controlled for a minimum of 3 months and the investigator has determined that the participant's mental status will not compromise the participant's ability to comply with protocol requirements may be enrolled
- Have an elevated blood pressure, systolic ≥ 150 mmHg or diastolic ≥ 90 mmHg, before challenge
- Taking any of the the protocol-defined drugs that are metabolized by CYP2C9 or any of the following psychiatric medications: aripiprazole, carbamazepine, chlorpromazine, chlorprothixene, clozapine, divalproex sodium, fluphenazine, haloperidol, lithium carbonate, lithium citrate, loxapine, mesoridazine, molindone, olanzapine, perphenazine, pimozide, quetiapine, risperidone, thioridazine, thiothixene, trifluoperazine, triflupromazine, or ziprasidone
- History of Guillain-Barré Syndrome
- Too low or too high a body mass index (BMI < 18.5 or > 39)
- Has an abnormal stool pattern defined as fewer than 3 stools per week or more than 2 stools per day within the past 6 months, and any loose stools (grade 3 or higher) during the 1-2 day acclimation period before challenge
- Has regularly used laxatives in the past 6 months
- Has a history of eating disorders (e.g. anorexia or bulimia) within the past 10 years
- Known allergy or previous severe adverse effect to all of the following antibiotics: ciprofloxacin (or quinolones), azithromycin and doxycycline.
- Previously received a licensed or investigational cholera vaccine, within 10 years
- History of cholera or enterotoxigenic Escherichia coli (ETEC) infection (lab-confirmed natural infection or experimental challenge), within 10 years
- Travel to a cholera-endemic area in the past 5 years
- Pregnant or nursing
- Positive serology for human immunodeficiency virus (HIV), hepatitis B antigen, or hepatitis C antibody
- Protocol-defined clinically abnormal 12-lead electrocardiogram (ECG) at screening in the judgment of the Investigator, or based on the formal 12-lead ECG reading by a cardiologist; history of any cardiac abnormalities, including conduction abnormalities such as Wolff-Parkinson-White, dysrhythmias, or coronary artery disease
- Presence of a clinically significant abnormality on physical examination, including (but not limited to): pathologic heart murmur, lymphadenopathy, hepatosplenomegaly, large abdominal scar of unclear origin
- Has poor venous access, defined as the inability to obtain screening blood tests after three attempts
- Currently on, or plans to be on, antibiotics (e.g., doxycycline) within 14 days prior to challenge and through 28 days after challenge
- Presence of an acute illness or fever (> 100.4°F) within 72 hours of admission to the inpatient Clinical Research Unit
- Taking any prescription or over-the-counter medications that contain aspirin, non-steroidal anti-inflammatory drugs (NSAIDs), antacids, proton pump inhibitors (PPIs), anti-diarrheals, etc. within 72 hours prior to challenge
- Received an investigational product within 30 days prior to randomization (90 days prior to randomization for monoclonal antibodies) or planned to participate in another research study involving an investigational product during the conduct of this study
- Participants must not have donated blood in 8 weeks prior to study entry and agreed to not donate blood during and for 4 weeks following their active participation in this study
- Lack of ability to fully understand the informed consent
- Any other condition(s) that in the opinion of the investigator would jeopardize the safety or rights of a participant participating in the trial or would render the participant unable to comply with the protocol
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase 2a Randomized, Single-Center, Double-Blind, Placebo Controlled Study to Evaluate the Safety and Preliminary Efficacy of Oral iOWH032 Against Cholera Diarrhea in a Controlled Human Infection Model
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.
Read the 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.
- Conditions
- Cholera
- Being tested
- iOWH032, Placebo, V. cholerae Challenge, Antibiotics
- Medical subject headings
- Cholera
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
iOWH032Drug
Anti-secretory synthetically manufactured small molecule designed to inhibit the cystic fibrosis transmembrane conductance regulator chloride channel.
PlaceboDrug
Oral tablets matching iOWH032 on taste, appearance, dissolution time with the same excipients but no active ingredients.
V. cholerae ChallengeOther
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.
AntibioticsDrug
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)
| Study group | Role | What they receive |
|---|---|---|
| iOWH032 | Experimental | On Day 1, participants were challenged with 10^6 colony-forming units (CFU) of freshly-harvested wild-type V. cholerae. At the onset of diarrhea, or at 48 hours after challenge, whichever occurred 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. Receives: Drug: iOWH032; Other: V. cholerae Challenge; Drug: Antibiotics |
| Placebo | Placebo comparator | 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 occurred 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. Receives: Drug: Placebo; Other: V. cholerae Challenge; Drug: Antibiotics |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Day 1 - Day 5 (up to first dose of antibiotic therapy)
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.
Measured: Day 1 - Day 5 (up to first dose of antibiotic therapy)
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:
- Death
- A life-threatening event.
- Required inpatient hospitalization or prolongation of existing hospitalization
- Resulted in persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions
- Congenital abnormality or birth defect
- 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.
Measured: Day 1 - Day 180
Secondary outcomes (10)
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.
Measured: Day 1 - Day 5 (up to first dose of antibiotic therapy)
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.
Measured: Day 1 - Day 5 (up to first dose of antibiotic therapy)
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.
Measured: Day 1 to Day 5 (prior to first dose of antibiotic)
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.
Measured: Day 1 to Day 5 (prior to first dose of antibiotic)
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.
Measured: Day 1 to Day 5 (prior to first dose of antibiotics)
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.
Measured: Day 1 to Day 5 (prior to first dose of antibiotic therapy)
Percentage of Participants With Fever Following Cholera Challenge
The presence of fever was defined as a body temperature of ≥ 39°C (102.1°F).
Measured: Day 1 to Day 5, prior to first dose of antibiotics
Percentage of Participants With Vomiting Following Cholera Challenge
Measured: Day 1 to Day 5, prior to first dose of antibiotics
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)
Measured: Day 1 - Day 8
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.
Measured: From first dose of study drug up to Day 29
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Nov 2019
- Study start4 Nov 2019
- Primary completion27 Jul 2020
- Study completion27 Jul 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for CholeraStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 47 participants (actual)
Sponsor and investigators
- Lead sponsor
- PATH
- Sponsor type
- University, hospital or other
- Collaborators
- University of Maryland, Baltimore, Pharmaron
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04150250
- Sponsor's protocol ID
- DRG-032-PO-2-01-USA
- Acronym
- CAST
- Status last verified
- Feb 2021
- First submitted
- 31 Oct 2019
- Last updated
- 25 Mar 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Erdem R, Ambler G, Al-Ibrahim M, Fraczek K, Dong SD, Gast C, Mercer LD, Raine M, Tennant SM, Chen WH, de Hostos EL, Choy RKM. A Phase 2a randomized, single-center, double-blind, placebo-controlled study to evaluate the safety and preliminary efficacy of oral iOWH032 against cholera diarrhea in a controlled human infection model. PLoS Negl Trop Dis. 2021 Nov 18;15(11):e0009969. doi: 10.1371/journal.pntd.0009969. eCollection 2021 Nov.
PubMed 34793441
Study at a glance
From the registry record, last updated by the sponsor on 25 Mar 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2a Randomized, Single-Center, Double-Blind, Placebo Controlled Study to Evaluate the Safety and Preliminary Efficacy of Oral iOWH032 Against Cholera Diarrhea in a Controlled Human Infection Model
- ClinicalTrials.gov ID
- NCT04150250
- Acronym / sponsor ID
- CAST / DRG-032-PO-2-01-USA
- Conditions
- Cholera
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 47 participants (actual)
- Lead sponsor
- PATHUniversity, hospital or other
- Collaborators
- University of Maryland, Baltimore, Pharmaron
- Study start
- 4 Nov 2019 (actual)
- Primary completion
- 27 Jul 2020 (actual)
- Study completion
- 27 Jul 2020 (actual)
- First posted
- 4 Nov 2019 (actual)
- Results
- Posted 25 Mar 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| iOWH032 | Experimental | Drug: iOWH032, Other: V. cholerae Challenge, Drug: AntibioticsOn Day 1, participants were challenged with 10^6 colony-forming units (CFU) of freshly-harvested wild-type V. cholerae. At the onset of diarrhea, or at 48 hours after challenge, whichever occurred 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. |
| Placebo | Placebo comparator | Drug: Placebo, Other: V. cholerae Challenge, Drug: AntibioticsOn 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 occurred 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. |
Who may qualify
- Ages
- 18 to 44 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (7 listed)
- Willing and able to understand and provide written informed consent
- 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
- All women must have a negative serum pregnancy test at screening and one day prior to challenge.
- Agreement by participants to use an adequate method of contraception* during the study and for 4 weeks before and after the challenge.
- 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.
Key exclusion criteria (30 listed)
- Clinically significant history of immunodeficiency, cardiovascular disease, respiratory disease, endocrine disorder, liver disease, renal disease, gastrointestinal disease, anal or rectal disorders, neurologic disease,
- Current nicotine use or drug, alcohol abuse within the past 6 months
- Recipient of bone marrow or solid organ transplant
- Use of systemic chemotherapy in the past 5 years
- Has a malignancy (excluding localized non-melanoma skin cancers) or lymphoproliferative disorders diagnosed or treated within the past 5 years
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| iOWH032Anti-secretory synthetically manufactured small molecule designed to inhibit the cystic fibrosis transmembrane conductance regulator chloride channel. | Drug | iOWH032 |
| PlaceboOral tablets matching iOWH032 on taste, appearance, dissolution time with the same excipients but no active ingredients. | Drug | Placebo |
| V. cholerae ChallengeFreshly-harvested, wild-type Vibrio (V.) cholerae El Tor Inaba strain N16961,10^6 cfu suspended in 30 mL of sodium bicarbonate solution ingested orally. | Other | Placebo, iOWH032 |
| AntibioticsAntibiotic 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) | Drug | Placebo, iOWH032 |
Primary outcome
Diarrheal Stool Output Rate
Time frame: 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
Time frame: 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
Time frame: 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.
10 secondary outcomes
Percentage of Participants With Moderate to Severe Diarrhea With Onset Within 48 Hours Following Cholera Challenge
Time frame: Day 1 - Day 5 (up to first dose of antibiotic therapy)
Attack Rate of Any Diarrhea Following Cholera Challenge
Time frame: Day 1 - Day 5 (up to first dose of antibiotic therapy)
Area Under the Curve (AUC) of Diarrheal Stool Volume Between Challenge Dose and Initiation of Antibiotics
Time frame: Day 1 to Day 5 (prior to first dose of antibiotic)
Peak Shedding of Cholera Organisms
Time frame: Day 1 to Day 5 (prior to first dose of antibiotic)
Duration of Diarrheal Episodes
Time frame: Day 1 to Day 5 (prior to first dose of antibiotics)
Total Number of Loose (Grade 3-5) Stools
Time frame: Day 1 to Day 5 (prior to first dose of antibiotic therapy)
Percentage of Participants With Fever Following Cholera Challenge
Time frame: Day 1 to Day 5, prior to first dose of antibiotics
Percentage of Participants With Vomiting Following Cholera Challenge
Time frame: Day 1 to Day 5, prior to first dose of antibiotics
Number of Participants With Solicited Adverse Effects
Time frame: Day 1 - Day 8
Number of Participants With Unsolicited Treatment-emergent Adverse Events (TEAE)
Time frame: From first dose of study drug up to Day 29
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Mar 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 34793441Erdem R, Ambler G, Al-Ibrahim M, Fraczek K, Dong SD, Gast C, Mercer LD, Raine M, Tennant SM, Chen WH, de Hostos EL, Choy RKM. A Phase 2a randomized, single-center, double-blind, placebo-controlled study to evaluate the safety and preliminary efficacy of oral iOWH032 against cholera diarrhea in a controlled human infection model. PLoS Negl Trop Dis. 2021 Nov 18;15(11):e0009969. doi: 10.1371/journal.pntd.0009969. eCollection 2021 Nov.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing iOWH032, V. cholerae Challenge and Antibiotics in people with Cholera, run by PATH at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 30 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 25 Mar 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 25 Mar 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Diarrheal Stool Output Rate (time frame: Day 1 - Day 5 (up to first dose of antibiotic therapy)). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04150250, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Mar 2021.