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| Name | Class |
|---|---|
| University of Maryland, Baltimore | OTHER |
| Pharmaron | INDUSTRY |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
|
| 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| iOWH032 | Drug | Anti-secretory synthetically manufactured small molecule designed to inhibit the cystic fibrosis transmembrane conductance regulator chloride channel. |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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:
The definition of diarrhea is a grade 3 or higher stool. | 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:
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. | 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:
|
| Measure | Description | Time Frame |
|---|---|---|
| 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:
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. |
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Inclusion Criteria:
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.
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Pharmaron | Baltimore | Maryland | 21201 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 34793441 | Derived | 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. |
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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.
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.
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| ID | Title | Description |
|---|---|---|
| FG000 | iOWH032 | 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 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. |
| FG001 | 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. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
All enrolled participants
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| ID | Title | Description |
|---|---|---|
| BG000 | 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. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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:
The definition of diarrhea is a grade 3 or higher stool. | 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. | Posted | Median | Inter-Quartile Range | mL/hour | Day 1 - Day 5 (up to first dose of antibiotic therapy) |
|
Serious adverse events and deaths were collected from first dose of study drug up to Day 180. Non-serious adverse events are reported from first dose of study drug up to Day 29.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | iOWH032 | On Day 1, participants were challenged with 10^6 CFU 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. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Pyelonephritis | Infections and infestations | MedDRA (22.1) | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Nausea | Gastrointestinal disorders | MedDRA (22.1) | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Gwen Ambler | PATH | 206-285-3500 | gambler@path.org |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Mar 13, 2020 | Feb 28, 2021 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Nov 25, 2020 | Feb 28, 2021 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D002771 | Cholera |
| ID | Term |
|---|---|
| D014735 | Vibrio Infections |
| D016905 | Gram-Negative Bacterial Infections |
| D001424 | Bacterial Infections |
| D001423 | Bacterial Infections and Mycoses |
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| ID | Term |
|---|---|
| C000720749 | IOWH-032 |
| D000900 | Anti-Bacterial Agents |
| ID | Term |
|---|---|
| D000890 | Anti-Infective Agents |
| D045506 | Therapeutic Uses |
| D020228 | Pharmacologic Actions |
| D020164 | Chemical Actions and Uses |
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| Placebo | Drug | Oral tablets matching iOWH032 on taste, appearance, dissolution time with the same excipients but no active ingredients. |
|
| V. cholerae Challenge | Other | 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. |
|
| Antibiotics | Drug | Antibiotic therapy may include:
|
|
| Day 1 - Day 180 |
| 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. | 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. | 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. | 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. | 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. | 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). | Day 1 to Day 5, prior to first dose of antibiotics |
| 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 | 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) | 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. | From first dose of study drug up to Day 29 |
| BG001 | 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. |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Count of Participants | Participants |
|
| Blood Type | Count of Participants | Participants |
|
| iOWH032 |
On Day 1, participants were challenged with 10^6 CFU 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. |
| OG001 | Placebo | On Day 1, participants were challenged with 10^6 CFU 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. |
|
|
|
| Primary | Diarrheal Stool Output Rate Including Participants With Symptom Onset After 48 Hours | Stools were graded based on consistency as follows:
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. | 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. | Posted | Median | Inter-Quartile Range | mL/hour | Day 1 - Day 5 (up to first dose of antibiotic therapy) |
|
|
|
|
| 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:
| All participants who received any study drug. | Posted | Count of Participants | Participants | Day 1 - Day 180 |
|
|
|
| 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:
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. | 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. | Posted | Number | 95% Confidence Interval | percentage of participants | Day 1 - Day 5 (up to first dose of antibiotic therapy) |
|
|
|
|
| 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. | 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. | Posted | Number | 95% Confidence Interval | percentage of participants | Day 1 - Day 5 (up to first dose of antibiotic therapy) |
|
|
|
|
| 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. | 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. | Posted | Median | Inter-Quartile Range | liters * hours | Day 1 to Day 5 (prior to first dose of antibiotic) |
|
|
|
|
| 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. | 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. | Posted | Mean | Standard Deviation | CFU/g | Day 1 to Day 5 (prior to first dose of antibiotic) |
|
|
|
| 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. | 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. | Posted | Median | Full Range | hours | Day 1 to Day 5 (prior to first dose of antibiotics) |
|
|
|
|
| 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. | 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. | Posted | Median | Inter-Quartile Range | loose stools | Day 1 to Day 5 (prior to first dose of antibiotic therapy) |
|
|
|
|
| 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). | 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. | Posted | Number | 95% Confidence Interval | percentage of participants | Day 1 to Day 5, prior to first dose of antibiotics |
|
|
|
|
| Secondary | Percentage of Participants With Vomiting Following Cholera Challenge | 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. | Posted | Number | 95% Confidence Interval | percentage of participants | Day 1 to Day 5, prior to first dose of antibiotics |
|
|
|
|
| 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) | All participants who received any study drug. | Posted | Count of Participants | Participants | Day 1 - Day 8 |
|
|
|
| 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. | All participants who received any study drug. | Posted | Count of Participants | Participants | From first dose of study drug up to Day 29 |
|
|
|
| 0 |
| 23 |
| 0 |
| 23 |
| 18 |
| 23 |
| EG001 | Placebo | On Day 1, participants were challenged with 10^6 CFU 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. | 0 | 24 | 1 | 24 | 21 | 24 |
| Diarrhoea | Gastrointestinal disorders | MedDRA (22.1) | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA (22.1) | Systematic Assessment |
|
| Abdominal discomfort | Gastrointestinal disorders | MedDRA (22.1) | Systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | MedDRA (22.1) | Systematic Assessment |
|
| Haematochezia | Gastrointestinal disorders | MedDRA (22.1) | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | MedDRA (22.1) | Systematic Assessment |
|
| Abdominal distension | Gastrointestinal disorders | MedDRA (22.1) | Systematic Assessment |
|
| Anal haemorrhage | Gastrointestinal disorders | MedDRA (22.1) | Systematic Assessment |
|
| Dry mouth | Gastrointestinal disorders | MedDRA (22.1) | Systematic Assessment |
|
| Dyspepsia | Gastrointestinal disorders | MedDRA (22.1) | Systematic Assessment |
|
| Frequent bowel movements | Gastrointestinal disorders | MedDRA (22.1) | Systematic Assessment |
|
| Gingival bleeding | Gastrointestinal disorders | MedDRA (22.1) | Systematic Assessment |
|
| Gingival pain | Gastrointestinal disorders | MedDRA (22.1) | Systematic Assessment |
|
| Haematemesis | Gastrointestinal disorders | MedDRA (22.1) | Systematic Assessment |
|
| Pyrexia | General disorders | MedDRA (22.1) | Systematic Assessment |
|
| Chills | General disorders | MedDRA (22.1) | Systematic Assessment |
|
| Pain | General disorders | MedDRA (22.1) | Systematic Assessment |
|
| Chest discomfort | General disorders | MedDRA (22.1) | Systematic Assessment |
|
| Influenza like illness | General disorders | MedDRA (22.1) | Systematic Assessment |
|
| Malaise | General disorders | MedDRA (22.1) | Systematic Assessment |
|
| Asthenia | General disorders | MedDRA (22.1) | Systematic Assessment |
|
| Fatigue | General disorders | MedDRA (22.1) | Systematic Assessment |
|
| Suprapubic pain | General disorders | MedDRA (22.1) | Systematic Assessment |
|
| Thirst | General disorders | MedDRA (22.1) | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA (22.1) | Systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA (22.1) | Systematic Assessment |
|
| Alanine aminotransferase increased | Investigations | MedDRA (22.1) | Systematic Assessment |
|
| Blood potassium decreased | Investigations | MedDRA (22.1) | Systematic Assessment |
|
| Aspartate aminotransferase increased | Investigations | MedDRA (22.1) | Systematic Assessment |
|
| Blood creatine phosphokinase increased | Investigations | MedDRA (22.1) | Systematic Assessment |
|
| Full blood count increased | Investigations | MedDRA (22.1) | Systematic Assessment |
|
| Blood bilirubin increased | Investigations | MedDRA (22.1) | Systematic Assessment |
|
| Sinus tachycardia | Cardiac disorders | MedDRA (22.1) | Systematic Assessment |
|
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA (22.1) | Systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA (22.1) | Systematic Assessment |
|
| Nasal congestion | Respiratory, thoracic and mediastinal disorders | MedDRA (22.1) | Systematic Assessment |
|
| Dysphonia | Respiratory, thoracic and mediastinal disorders | MedDRA (22.1) | Systematic Assessment |
|
| Decreased appetite | Metabolism and nutrition disorders | MedDRA (22.1) | Systematic Assessment |
|
| Candida infection | Infections and infestations | MedDRA (22.1) | Systematic Assessment |
|
| Nasopharyngitis | Infections and infestations | MedDRA (22.1) | Systematic Assessment |
|
| Upper respiratory tract infection | Infections and infestations | MedDRA (22.1) | Systematic Assessment |
|
| Vulvovaginal mycotic infection | Infections and infestations | MedDRA (22.1) | Systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA (22.1) | Systematic Assessment |
|
| Muscle spasms | Musculoskeletal and connective tissue disorders | MedDRA (22.1) | Systematic Assessment |
|
| Rash | Skin and subcutaneous tissue disorders | MedDRA (22.1) | Systematic Assessment |
|
| Photosensitivity reaction | Skin and subcutaneous tissue disorders | MedDRA (22.1) | Systematic Assessment |
|
Not provided
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| D007239 | Infections |
| Headache |
|
| Malaise |
|
| Nausea |
|
| TEAE leading to discontinuation from study |
|
| TEAE leading to death |
|