Cholera Anti-Secretory Treatment Trial
Cholera Anti-Secretory Treatment Trial
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.
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.
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 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

 8. Have an elevated blood pressure, systolic ≥ 150 mmHg or diastolic ≥ 90 mmHg, before
 challenge

 9. 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

 10. History of Guillain-Barré Syndrome

 11. Too low or too high a body mass index (BMI < 18.5 or > 39)

 12. 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

 13. Has regularly used laxatives in the past 6 months

 14. Has a history of eating disorders (e.g. anorexia or bulimia) within the past 10 years

 15. Known allergy or previous severe adverse effect to all of the following antibiotics:
 ciprofloxacin (or quinolones), azithromycin and doxycycline.

 16. Previously received a licensed or investigational cholera vaccine, within 10 years

 17. History of cholera or enterotoxigenic Escherichia coli (ETEC) infection (lab-confirmed
 natural infection or experimental challenge), within 10 years

 18. Travel to a cholera-endemic area in the past 5 years

 19. Pregnant or nursing

 20. Positive serology for human immunodeficiency virus (HIV), hepatitis B antigen, or
 hepatitis C antibody

 21. 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

 22. 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

 23. Has poor venous access, defined as the inability to obtain screening blood tests after
 three attempts

 24. Currently on, or plans to be on, antibiotics (e.g., doxycycline) within 14 days prior
 to challenge and through 28 days after challenge

 25. Presence of an acute illness or fever (> 100.4°F) within 72 hours of admission to the
 inpatient Clinical Research Unit

 26. 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

 27. 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

 28. 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

 29. Lack of ability to fully understand the informed consent

 30. 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