Trial Outcomes & Findings for Safety and Pharmacokinetics of UV-4B Solution Administered Orally as Multiple Ascending Doses to Healthy Subjects (NCT NCT02696291)

NCT ID: NCT02696291

Last Updated: 2024-03-18

Results Overview

The incidence of TEAEs spontaneously reported by subjects or elicited during examination is reported by dose group. Subjects having multiple TEAEs are counted only once.

• Recruitment status: TERMINATED
• Study phase: PHASE1
• Target enrollment: 7 participants
• Primary outcome timeframe: From the time of first dosing on Day 1 through the Day 15 final follow-up visit
• Results posted on: 2024-03-18

Participant Flow

Healthy subjects were recruited from a phase 1 clinical research unit. Recruitment was initiated on 27 May 2016 and the last subject completed the final study visit for Cohort 1 on 02 March 2017.

Participant milestones

Measure	Cohort 1 - 30 mg UV-4B Subjects receiving UV-4B 30 mg oral solution TID (every 8 ± 0.5 hours) for 7 days	Cohort 1 - Placebo Subjects receiving placebo TID (every 8 ± 0.5 hours) for 7 days
Overall Study STARTED	5	2
Overall Study COMPLETED	5	2
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Safety and Pharmacokinetics of UV-4B Solution Administered Orally as Multiple Ascending Doses to Healthy Subjects

Baseline characteristics by cohort

Measure	Cohort 1 - 30 mg UV-4B n=5 Participants Subjects receiving UV-4B 30 mg oral solution TID (every 8 ± 0.5 hours) for 7 days	Cohort 1 - Placebo n=2 Participants Subjects receiving placebo TID (every 8 ± 0.5 hours) for 7 days	Total n=7 Participants Total of all reporting groups
Age, Continuous	31.2 years STANDARD_DEVIATION 8.3 • n=5 Participants	41.5 years STANDARD_DEVIATION 4.9 • n=7 Participants	34.1 years STANDARD_DEVIATION 8.7 • n=5 Participants
Sex: Female, Male Female	3 Participants n=5 Participants	2 Participants n=7 Participants	5 Participants n=5 Participants
Sex: Female, Male Male	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	3 Participants n=5 Participants	1 Participants n=7 Participants	4 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) White	4 Participants n=5 Participants	2 Participants n=7 Participants	6 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Body Mass Index	26.0 kg/m^2 STANDARD_DEVIATION 1.0 • n=5 Participants	28.4 kg/m^2 STANDARD_DEVIATION 2.3 • n=7 Participants	26.7 kg/m^2 STANDARD_DEVIATION 1.7 • n=5 Participants

PRIMARY outcome

Timeframe: From the time of first dosing on Day 1 through the Day 15 final follow-up visit

Population: Safety Population: all subjects who received at least one dose of study product or placebo.

The incidence of TEAEs spontaneously reported by subjects or elicited during examination is reported by dose group. Subjects having multiple TEAEs are counted only once.

Outcome measures

Measure	Cohort 1 - 30 mg UV-4B n=5 Participants Subjects receiving UV-4B 30 mg oral solution TID (every 8 ± 0.5 hours) for 7 days	Cohort 1 - Placebo n=2 Participants Subjects receiving placebo TID (every 8 ± 0.5 hours) for 7 days
Number of Subjects Reporting Treatment-emergent Adverse Events (TEAEs) by Group	5 Participants	2 Participants

PRIMARY outcome

Timeframe: From the time of first dosing on Day 1 through the Day 15 final follow-up visit

Population: Safety Population: all subjects who received at least one dose of study product or placebo.

The incidence of SAEs spontaneously reported by subjects or elicited during examination is reported by dose group. Subjects having multiple SAEs are counted only once.

Outcome measures

Measure	Cohort 1 - 30 mg UV-4B n=5 Participants Subjects receiving UV-4B 30 mg oral solution TID (every 8 ± 0.5 hours) for 7 days	Cohort 1 - Placebo n=2 Participants Subjects receiving placebo TID (every 8 ± 0.5 hours) for 7 days
Number of Subjects Reporting Serious Adverse Events (SAEs) by Group	1 Participants	0 Participants

PRIMARY outcome

Timeframe: From the time of first dosing on Day 1 through the Day 15 final follow-up visit

Population: Safety Population: all subjects who received at least one dose of study product or placebo.

Clinical laboratory abnormalities are presented as the total of Grade 1 (mild) through Grade 4 (potentially life-threatening) abnormalities according to criteria adapted from the Food and Drug Administration (FDA) Guidance for Industry, Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials (September 2007) and the Division of Microbiology and Infectious Diseases (DMID) Adult Toxicity Table (November 2007). Within each parameter, subjects having multiple abnormalities are counted only once.

Outcome measures

Measure	Cohort 1 - 30 mg UV-4B n=5 Participants Subjects receiving UV-4B 30 mg oral solution TID (every 8 ± 0.5 hours) for 7 days	Cohort 1 - Placebo n=2 Participants Subjects receiving placebo TID (every 8 ± 0.5 hours) for 7 days
Number of Subjects With Clinical Laboratory Abnormalities of Toxicity Grade 1 or Higher by Group ≥ Grade 1 magnesium decreased	0 Participants	1 Participants
Number of Subjects With Clinical Laboratory Abnormalities of Toxicity Grade 1 or Higher by Group Any ≥ Grade 1 result	5 Participants	2 Participants
Number of Subjects With Clinical Laboratory Abnormalities of Toxicity Grade 1 or Higher by Group ≥ Grade 1 activated partial thromboplastin time	1 Participants	0 Participants
Number of Subjects With Clinical Laboratory Abnormalities of Toxicity Grade 1 or Higher by Group ≥ Grade 1 hemoglobin decreased	5 Participants	2 Participants
Number of Subjects With Clinical Laboratory Abnormalities of Toxicity Grade 1 or Higher by Group ≥ Grade 1 leukocytes decreased	1 Participants	0 Participants
Number of Subjects With Clinical Laboratory Abnormalities of Toxicity Grade 1 or Higher by Group ≥ Grade 1 prothrombin time increased	4 Participants	1 Participants
Number of Subjects With Clinical Laboratory Abnormalities of Toxicity Grade 1 or Higher by Group ≥ Grade 1 sodium decreased	1 Participants	0 Participants
Number of Subjects With Clinical Laboratory Abnormalities of Toxicity Grade 1 or Higher by Group ≥ Grade 1 urine erythrocytes (present)	4 Participants	2 Participants

SECONDARY outcome

Timeframe: From the time of first dosing on Day 1 through the Day 15 final follow-up visit

Population: Safety Population: all subjects who received at least one dose of study product or placebo.

Vital signs of blood pressure (BP), pulse, respiratory rate, and oral temperature were taken after being supine for 10 minutes. Orthostatic vital signs (BP, pulse) were taken after 2 minutes standing. Vital sign results are presented as the number of subjects having Grade 1 (mild) through Grade 4 (potentially life-threatening) abnormalities according to criteria adapted from the FDA Guidance for Industry, Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials (September 2007), or having abnormal orthostatic change (standing minus supine result). Within each parameter, subjects having multiple abnormalities are counted only once.

Outcome measures

Measure	Cohort 1 - 30 mg UV-4B n=5 Participants Subjects receiving UV-4B 30 mg oral solution TID (every 8 ± 0.5 hours) for 7 days	Cohort 1 - Placebo n=2 Participants Subjects receiving placebo TID (every 8 ± 0.5 hours) for 7 days
Number of Subjects With Outlying Vital Sign Results by Group Any ≥ Grade 1 result	5 Participants	2 Participants
Number of Subjects With Outlying Vital Sign Results by Group ≥ Grade 1 supine systolic BP ≤ 89 mmHg	1 Participants	0 Participants
Number of Subjects With Outlying Vital Sign Results by Group ≥ Grade 1 supine pulse ≤ 50 bpm (if baseline ≤ 60)	1 Participants	0 Participants
Number of Subjects With Outlying Vital Sign Results by Group ≥ Grade 1 supine pulse ≤ 54 bpm (if baseline > 60)	1 Participants	0 Participants
Number of Subjects With Outlying Vital Sign Results by Group ≥ Grade 1 supine pulse ≥ 101 bpm	0 Participants	1 Participants
Number of Subjects With Outlying Vital Sign Results by Group ≥ Grade 1 respiratory rate ≥ 17 breaths/min	2 Participants	1 Participants
Number of Subjects With Outlying Vital Sign Results by Group Any orthostatic change	5 Participants	2 Participants
Number of Subjects With Outlying Vital Sign Results by Group Orthostatic change in diastolic BP ≤ -10 mmHg	1 Participants	1 Participants
Number of Subjects With Outlying Vital Sign Results by Group Orthostatic change in pulse > 30 bpm	5 Participants	1 Participants

SECONDARY outcome

Timeframe: From the time of first dosing on Day 1 through the Day 15 final follow-up visit

Population: Safety Population: all subjects who received at least one dose of study product or placebo.

ECGs (ventricular heart rate, wave intervals - PR, QRS, QT, QTcF) were recorded in a supine position (for at least 10 minutes). Baseline was calculated from the average of the triplicate ECGs on Day 1 predose. Within each parameter, subjects having multiple abnormalities are counted only once.

Outcome measures

Measure	Cohort 1 - 30 mg UV-4B n=5 Participants Subjects receiving UV-4B 30 mg oral solution TID (every 8 ± 0.5 hours) for 7 days	Cohort 1 - Placebo n=2 Participants Subjects receiving placebo TID (every 8 ± 0.5 hours) for 7 days
Number of Subjects With 12-lead Electrocardiogram (ECG) Abnormalities Postdose by Group Any ECG abnormality	2 Participants	0 Participants
Number of Subjects With 12-lead Electrocardiogram (ECG) Abnormalities Postdose by Group PR > 220 ms	2 Participants	0 Participants

SECONDARY outcome

Timeframe: Day 1, Day 7

Population: Pharmacokinetic Population: all subjects who received study product, had measurable values, and completed scheduled postdose pharmacokinetic measurements without protocol deviations or events thought to significantly affect the pharmacokinetics of the drug.

Plasma concentrations of UV-4 are determined by means of high performance liquid chromatography/tandem mass spectrometric assay. Values of Cmax are derived from individual subject plasma concentration-time data. Blood collected at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 5, 6, and 8 hrs after the first dose on Day 1; and at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 5, 6, 8, 10, 12, and 14 hrs after the final dose on Day 7.

Outcome measures

Measure	Cohort 1 - 30 mg UV-4B n=5 Participants Subjects receiving UV-4B 30 mg oral solution TID (every 8 ± 0.5 hours) for 7 days	Cohort 1 - Placebo Subjects receiving placebo TID (every 8 ± 0.5 hours) for 7 days
Maximum Plasma Concentration (Cmax) Day 1 Cmax	291 ng/mL Geometric Coefficient of Variation 15.8	—
Maximum Plasma Concentration (Cmax) Day 7 Cmax	285 ng/mL Geometric Coefficient of Variation 5.1	—

SECONDARY outcome

Timeframe: Day 1, Day 7

Population: Pharmacokinetic Population: all subjects who received study product, had measurable values, and completed scheduled postdose pharmacokinetic measurements without protocol deviations or events thought to significantly affect the pharmacokinetics of the drug.

Plasma concentrations of UV-4 are determined by means of high performance liquid chromatography/tandem mass spectrometric assay. Values of tmax are derived from individual subject plasma concentration-time data. Blood collected at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 5, 6, and 8 hrs after the first dose on Day 1; and at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 5, 6, 8, 10, 12, and 14 hrs after the final dose on Day 7.

Outcome measures

Measure	Cohort 1 - 30 mg UV-4B n=5 Participants Subjects receiving UV-4B 30 mg oral solution TID (every 8 ± 0.5 hours) for 7 days	Cohort 1 - Placebo Subjects receiving placebo TID (every 8 ± 0.5 hours) for 7 days
Time of Maximum Plasma Concentration (Tmax) Day 1 tmax	0.7 h Standard Deviation 0.2	—
Time of Maximum Plasma Concentration (Tmax) Day 7 tmax	1.0 h Standard Deviation 0.4	—

SECONDARY outcome

Timeframe: Day 7

Population: Pharmacokinetic Population: all subjects who received study product, had measurable values, and completed scheduled postdose pharmacokinetic measurements without protocol deviations or events thought to significantly affect the pharmacokinetics of the drug.

Plasma concentrations of UV-4 are determined by means of high performance liquid chromatography/tandem mass spectrometric assay. Values of AUC(0-last) are derived from individual subject plasma concentration-time data, calculated using the linear trapezoidal rule for increasing concentrations and the logarithmic rule for decreasing concentrations. Blood collected at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 5, 6, 8, 10, 12, and 14 hrs after the final dose on Day 7.

Outcome measures

Measure	Cohort 1 - 30 mg UV-4B n=5 Participants Subjects receiving UV-4B 30 mg oral solution TID (every 8 ± 0.5 hours) for 7 days	Cohort 1 - Placebo Subjects receiving placebo TID (every 8 ± 0.5 hours) for 7 days
Area Under the Concentration-time Curve From Time Zero (Predose) to Time of the Last Quantifiable Concentration After the Last Dose [AUC(0-last)]	1800 ng*hr/mL Geometric Coefficient of Variation 14.2	—

SECONDARY outcome

Timeframe: Day 7

Population: Pharmacokinetic Population: all subjects who received study product, had measurable values, and completed scheduled postdose pharmacokinetic measurements without protocol deviations or events thought to significantly affect the pharmacokinetics of the drug.

Plasma concentrations of UV-4 are determined by means of high performance liquid chromatography/tandem mass spectrometric assay. Values of AUC(0-24) are derived from individual subject plasma concentration-time data, calculated as AUC(0-8) x 3 (Day 7 last dose only). Blood collected at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 5, 6, 8, 10, 12, and 14 hrs after the final dose on Day 7.

Outcome measures

Measure	Cohort 1 - 30 mg UV-4B n=5 Participants Subjects receiving UV-4B 30 mg oral solution TID (every 8 ± 0.5 hours) for 7 days	Cohort 1 - Placebo Subjects receiving placebo TID (every 8 ± 0.5 hours) for 7 days
Total Daily Exposure at Steady State: Area Under the Concentration-time Curve From Time Zero (Predose) Until 24 Hours After the Last Dose [AUC(0-24)]	3810 ng*hr/mL Geometric Coefficient of Variation 3.7	—

SECONDARY outcome

Timeframe: Day 1, Day 7

Population: Pharmacokinetic Population: all subjects who received study product, had measurable values, and completed scheduled postdose pharmacokinetic measurements without protocol deviations or events thought to significantly affect the pharmacokinetics of the drug.

Plasma concentrations of UV-4 are determined by means of high performance liquid chromatography/tandem mass spectrometric assay. Values of AUC(0-8) are derived from individual subject plasma concentration-time data, calculated using the linear trapezoidal rule for increasing concentrations and the logarithmic rule for decreasing concentrations. Blood collected at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 5, 6, and 8 hrs after the first dose on Day 1; and at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 5, 6, 8, 10, 12, and 14 hrs after the final dose on Day 7.

Outcome measures

Measure	Cohort 1 - 30 mg UV-4B n=5 Participants Subjects receiving UV-4B 30 mg oral solution TID (every 8 ± 0.5 hours) for 7 days	Cohort 1 - Placebo Subjects receiving placebo TID (every 8 ± 0.5 hours) for 7 days
Area Under the Concentration-time Curve From Time Zero (Predose) Until 8 Hours After the Final Dose [AUC(0-8)] Day 1 AUC(0-8)	965 ng*hr/mL Geometric Coefficient of Variation 8.7	—
Area Under the Concentration-time Curve From Time Zero (Predose) Until 8 Hours After the Final Dose [AUC(0-8)] Day 7 AUC(0-8)	1270 ng*hr/mL Geometric Coefficient of Variation 3.7	—

SECONDARY outcome

Timeframe: Day 7

Population: Pharmacokinetic Population: all subjects who received study product, had measurable values, and completed scheduled postdose pharmacokinetic measurements without protocol deviations or events thought to significantly affect the pharmacokinetics of the drug.

Plasma concentrations of UV-4 are determined by means of high performance liquid chromatography/tandem mass spectrometric assay. Values of CL/F are derived from individual subject plasma concentration-time data, calculated as dose (free-base equivalent) divided by AUC(0-8). Blood collected at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 5, 6, 8, 10, 12, and 14 hrs after the final dose on Day 7.

Outcome measures

Measure	Cohort 1 - 30 mg UV-4B n=5 Participants Subjects receiving UV-4B 30 mg oral solution TID (every 8 ± 0.5 hours) for 7 days	Cohort 1 - Placebo Subjects receiving placebo TID (every 8 ± 0.5 hours) for 7 days
Apparent Systemic Clearance (CL/F) at Steady State	23.6 L/h Geometric Coefficient of Variation 3.7	—

SECONDARY outcome

Timeframe: Day 7

Population: Pharmacokinetic Population: all subjects who received study product, had measurable values, and completed scheduled postdose pharmacokinetic measurements without protocol deviations or events thought to significantly affect the pharmacokinetics of the drug.

Plasma concentrations of UV-4 are determined by means of high performance liquid chromatography/tandem mass spectrometric assay. Values of Vz/F are derived from individual subject plasma concentration-time data, calculated as CL/F divided by λz. Blood collected at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 5, 6, 8, 10, 12, and 14 hrs after the final dose on Day 7.

Outcome measures

Measure	Cohort 1 - 30 mg UV-4B n=5 Participants Subjects receiving UV-4B 30 mg oral solution TID (every 8 ± 0.5 hours) for 7 days	Cohort 1 - Placebo Subjects receiving placebo TID (every 8 ± 0.5 hours) for 7 days
Apparent Volume of Distribution of UV-4 During the Terminal Phase (Vz/F) After Multiple Doses	246 L Geometric Coefficient of Variation 30.6	—

SECONDARY outcome

Timeframe: Day 7

Population: Pharmacokinetic Population: all subjects who received study product, had measurable values, and completed scheduled postdose pharmacokinetic measurements without protocol deviations or events thought to significantly affect the pharmacokinetics of the drug.

Plasma concentrations of UV-4 are determined by means of high performance liquid chromatography/tandem mass spectrometric assay. Values of t1/2 are derived from individual subject plasma concentration-time data, calculated as ln2/λz. Blood collected at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 5, 6, 8, 10, 12, and 14 hrs after the final dose on Day 7.

Outcome measures

Measure	Cohort 1 - 30 mg UV-4B n=5 Participants Subjects receiving UV-4B 30 mg oral solution TID (every 8 ± 0.5 hours) for 7 days	Cohort 1 - Placebo Subjects receiving placebo TID (every 8 ± 0.5 hours) for 7 days
Apparent Terminal Half Life (t1/2)	8.1 h Interval 4.1 to 9.0	—

SECONDARY outcome

Timeframe: Day 7

Population: Pharmacokinetic Population: all subjects who received study product, had measurable values, and completed scheduled postdose pharmacokinetic measurements without protocol deviations or events thought to significantly affect the pharmacokinetics of the drug.

Accumulation Ratio (AR) Day 1/Day 7

Outcome measures

Measure	Cohort 1 - 30 mg UV-4B n=5 Participants Subjects receiving UV-4B 30 mg oral solution TID (every 8 ± 0.5 hours) for 7 days	Cohort 1 - Placebo Subjects receiving placebo TID (every 8 ± 0.5 hours) for 7 days
Accumulation Ratio (AR)	1.3 Ratio Geometric Coefficient of Variation 5.8	—

Adverse Events

Cohort 1 - 30 mg UV-4B

Serious events: 1 serious events

Other events: 5 other events

Deaths: 0 deaths

Cohort 1 - Placebo

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Serious adverse events

Measure	Cohort 1 - 30 mg UV-4B n=5 participants at risk Subjects receiving UV-4B 30 mg oral solution TID (every 8 ± 0.5 hours) for 7 days	Cohort 1 - Placebo n=2 participants at risk Subjects receiving placebo TID (every 8 ± 0.5 hours) for 7 days
Gastrointestinal disorders Haemorrhoids	20.0% 1/5 • Number of events 1 • Up to Day 15. On-treatment SAEs and non-serious AEs were collected from the start of investigational product until Day 15.	0.00% 0/2 • Up to Day 15. On-treatment SAEs and non-serious AEs were collected from the start of investigational product until Day 15.

Other adverse events

Measure	Cohort 1 - 30 mg UV-4B n=5 participants at risk Subjects receiving UV-4B 30 mg oral solution TID (every 8 ± 0.5 hours) for 7 days	Cohort 1 - Placebo n=2 participants at risk Subjects receiving placebo TID (every 8 ± 0.5 hours) for 7 days
Cardiac disorders Atrioventricular block first degree	20.0% 1/5 • Number of events 1 • Up to Day 15. On-treatment SAEs and non-serious AEs were collected from the start of investigational product until Day 15.	0.00% 0/2 • Up to Day 15. On-treatment SAEs and non-serious AEs were collected from the start of investigational product until Day 15.
Cardiac disorders Bradycardia	20.0% 1/5 • Number of events 1 • Up to Day 15. On-treatment SAEs and non-serious AEs were collected from the start of investigational product until Day 15.	0.00% 0/2 • Up to Day 15. On-treatment SAEs and non-serious AEs were collected from the start of investigational product until Day 15.
Gastrointestinal disorders Flatulence	40.0% 2/5 • Number of events 2 • Up to Day 15. On-treatment SAEs and non-serious AEs were collected from the start of investigational product until Day 15.	0.00% 0/2 • Up to Day 15. On-treatment SAEs and non-serious AEs were collected from the start of investigational product until Day 15.
Gastrointestinal disorders Abdominal pain	20.0% 1/5 • Number of events 1 • Up to Day 15. On-treatment SAEs and non-serious AEs were collected from the start of investigational product until Day 15.	0.00% 0/2 • Up to Day 15. On-treatment SAEs and non-serious AEs were collected from the start of investigational product until Day 15.
Gastrointestinal disorders Constipation	20.0% 1/5 • Number of events 1 • Up to Day 15. On-treatment SAEs and non-serious AEs were collected from the start of investigational product until Day 15.	0.00% 0/2 • Up to Day 15. On-treatment SAEs and non-serious AEs were collected from the start of investigational product until Day 15.
Gastrointestinal disorders Diarrhoea	20.0% 1/5 • Number of events 1 • Up to Day 15. On-treatment SAEs and non-serious AEs were collected from the start of investigational product until Day 15.	0.00% 0/2 • Up to Day 15. On-treatment SAEs and non-serious AEs were collected from the start of investigational product until Day 15.
Gastrointestinal disorders Epigastric discomfort	20.0% 1/5 • Number of events 1 • Up to Day 15. On-treatment SAEs and non-serious AEs were collected from the start of investigational product until Day 15.	0.00% 0/2 • Up to Day 15. On-treatment SAEs and non-serious AEs were collected from the start of investigational product until Day 15.
Gastrointestinal disorders Gingival bleeding	20.0% 1/5 • Number of events 1 • Up to Day 15. On-treatment SAEs and non-serious AEs were collected from the start of investigational product until Day 15.	0.00% 0/2 • Up to Day 15. On-treatment SAEs and non-serious AEs were collected from the start of investigational product until Day 15.
General disorders Vessel puncture site haematoma	20.0% 1/5 • Number of events 1 • Up to Day 15. On-treatment SAEs and non-serious AEs were collected from the start of investigational product until Day 15.	50.0% 1/2 • Number of events 1 • Up to Day 15. On-treatment SAEs and non-serious AEs were collected from the start of investigational product until Day 15.
General disorders Vessel puncture site pain	20.0% 1/5 • Number of events 1 • Up to Day 15. On-treatment SAEs and non-serious AEs were collected from the start of investigational product until Day 15.	50.0% 1/2 • Number of events 1 • Up to Day 15. On-treatment SAEs and non-serious AEs were collected from the start of investigational product until Day 15.
General disorders Vessel puncture site haemorrhage	0.00% 0/5 • Up to Day 15. On-treatment SAEs and non-serious AEs were collected from the start of investigational product until Day 15.	50.0% 1/2 • Number of events 1 • Up to Day 15. On-treatment SAEs and non-serious AEs were collected from the start of investigational product until Day 15.
Investigations Haemoglobin decreased	100.0% 5/5 • Number of events 5 • Up to Day 15. On-treatment SAEs and non-serious AEs were collected from the start of investigational product until Day 15.	100.0% 2/2 • Number of events 2 • Up to Day 15. On-treatment SAEs and non-serious AEs were collected from the start of investigational product until Day 15.
Investigations Prothrombin time prolonged	80.0% 4/5 • Number of events 4 • Up to Day 15. On-treatment SAEs and non-serious AEs were collected from the start of investigational product until Day 15.	50.0% 1/2 • Number of events 1 • Up to Day 15. On-treatment SAEs and non-serious AEs were collected from the start of investigational product until Day 15.
Investigations Activated partial thromboplastin time	20.0% 1/5 • Number of events 1 • Up to Day 15. On-treatment SAEs and non-serious AEs were collected from the start of investigational product until Day 15.	0.00% 0/2 • Up to Day 15. On-treatment SAEs and non-serious AEs were collected from the start of investigational product until Day 15.
Investigations White blood cell count decreased	20.0% 1/5 • Number of events 1 • Up to Day 15. On-treatment SAEs and non-serious AEs were collected from the start of investigational product until Day 15.	0.00% 0/2 • Up to Day 15. On-treatment SAEs and non-serious AEs were collected from the start of investigational product until Day 15.
Metabolism and nutrition disorders Hypomagnesaemia	0.00% 0/5 • Up to Day 15. On-treatment SAEs and non-serious AEs were collected from the start of investigational product until Day 15.	50.0% 1/2 • Number of events 1 • Up to Day 15. On-treatment SAEs and non-serious AEs were collected from the start of investigational product until Day 15.
Metabolism and nutrition disorders Hyponatraemia	20.0% 1/5 • Number of events 1 • Up to Day 15. On-treatment SAEs and non-serious AEs were collected from the start of investigational product until Day 15.	0.00% 0/2 • Up to Day 15. On-treatment SAEs and non-serious AEs were collected from the start of investigational product until Day 15.
Nervous system disorders Dizziness	20.0% 1/5 • Number of events 1 • Up to Day 15. On-treatment SAEs and non-serious AEs were collected from the start of investigational product until Day 15.	0.00% 0/2 • Up to Day 15. On-treatment SAEs and non-serious AEs were collected from the start of investigational product until Day 15.
Nervous system disorders Headache	20.0% 1/5 • Number of events 1 • Up to Day 15. On-treatment SAEs and non-serious AEs were collected from the start of investigational product until Day 15.	0.00% 0/2 • Up to Day 15. On-treatment SAEs and non-serious AEs were collected from the start of investigational product until Day 15.
Renal and urinary disorders Haematuria	60.0% 3/5 • Number of events 3 • Up to Day 15. On-treatment SAEs and non-serious AEs were collected from the start of investigational product until Day 15.	100.0% 2/2 • Number of events 2 • Up to Day 15. On-treatment SAEs and non-serious AEs were collected from the start of investigational product until Day 15.
Reproductive system and breast disorders Testis discomfort	50.0% 1/2 • Number of events 1 • Up to Day 15. On-treatment SAEs and non-serious AEs were collected from the start of investigational product until Day 15.	0.00% 0/2 • Up to Day 15. On-treatment SAEs and non-serious AEs were collected from the start of investigational product until Day 15.

Additional Information

Tim Babinchak, MD

Emergent Product Development Gaithersburg, Inc.

Phone: (240) 631-3585

Email: tbabinchak@ebsi.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place