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Cholera Anti-Secretory Treatment Trial (CAST)

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ClinicalTrials.gov Identifier: NCT04150250
Recruitment Status : Not yet recruiting
First Posted : November 4, 2019
Last Update Posted : November 6, 2019
Sponsor:
Collaborators:
University of Maryland, Baltimore
Pharmaron
Information provided by (Responsible Party):
PATH

Brief Summary:
A single-center, randomized, double-blind, placebo-controlled trial to assess safety and preliminary efficacy of oral doses of iOWH032 on diarrhea output and clinical symptoms after a cholera challenge. A total of 48 healthy adult individuals will be enrolled and challenged with a cholera strain before being randomized to either iOWH032 or placebo for 3 days.

Condition or disease Intervention/treatment Phase
Cholera Drug: iOWH032 Drug: Placebo oral tablet Phase 2

Detailed Description:
This is a single-center, randomized, double-blind, placebo-controlled trial to evaluate the therapeutic efficacy of oral doses of iOWH032 on diarrhea output and clinical symptoms after a cholera challenge. There will be 24 study participants challenged in the first cohort and an additional 24 study participants challenged in the second cohort, pending favorable results of an interim analysis. 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 10^6 cfu of V. cholerae El Tor Inaba strain N16961. The observation and management of cholera diarrhea and symptomatology will occur on an inpatient isolation research ward over a duration of ~11 days, including a three-day course of antibiotics to treat all participants prior to discharge from the inpatient unit. The final study follow-up visit will be six months after the challenge via phone call.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 48 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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
Estimated Study Start Date : November 2019
Estimated Primary Completion Date : March 2020
Estimated Study Completion Date : August 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Cholera

Arm Intervention/treatment
Experimental: iOWH032
Oral iOWH032 500 mg tablets every 8 hours for 3 days
Drug: iOWH032
Anti-secretory synthetically manufactured small molecule designed to inhit the cystic fibrosis transmembrane conductance regulator chloride channel.

Placebo Comparator: Placebo
Oral matching placebo tablets every 8 hours for 3 days
Drug: Placebo oral tablet
Oral tablets matching iOWH032 on taste, appearance, dissolution time with the same excipients but no active ingredients.




Primary Outcome Measures :
  1. Diarrheal stool output rate [ Time Frame: Day 1 - Day 5 ]
    Diarrheal stool output rate, 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 antimicrobial therapy.

  2. Treatment emergent serious adverse events [ Time Frame: Day 1 - Day 180 ]
    Frequency and incidence of serious adverse events (SAEs) throughout the study



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 44 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

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 as 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 drugs listed in Appendix F 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 BMI (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 (appendix B) clinically abnormal 12-lead 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 ( for the monoclonal antibodies- 90 days prior to randomization) or planning to participate in another research study involving 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04150250


Contacts
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Contact: Gwen Ambler, MPH 206-302-4673 gambler@path.org

Sponsors and Collaborators
PATH
University of Maryland, Baltimore
Pharmaron

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Responsible Party: PATH
ClinicalTrials.gov Identifier: NCT04150250     History of Changes
Other Study ID Numbers: DRG-032-PO-2-01-USA
First Posted: November 4, 2019    Key Record Dates
Last Update Posted: November 6, 2019
Last Verified: November 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Cholera
Vibrio Infections
Gram-Negative Bacterial Infections
Bacterial Infections