Trial Outcomes & Findings for CM4620 Injectable Emulsion Versus Supportive Care in Patients With Acute Pancreatitis and SIRS (NCT NCT03401190)

Last Updated: 2021-12-07

Results Overview

Safety and tolerability will be assessed by monitoring the frequency, duration and severity of treatment-emergent adverse events (TEAEs) throughout the study period.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

21 participants

Primary outcome timeframe

90 Days

Results posted on

2021-12-07

Participant Flow

Participant milestones

Participant milestones
Measure	Low Dose Group Patients were randomized to receive CM4620-IE 1.0 mg/kg on Days 1 and 1.4 mg/kg on Days 2-4. All doses of CM4620-IE were administered intravenously (IV) over 4 hours.	High Dose Group Patients were randomized to receive CM4620-IE 2.08 mg/kg on Days 1 and 2, and 1.6 mg/kg on Days 3-4. All doses of CM4620-IE will be administered intravenously (IV) over 4 hours.	Standard of Care Group Patients were randomized to receive local standard of care.
Overall Study STARTED	8	6	7
Overall Study COMPLETED	8	4	7
Overall Study NOT COMPLETED	0	2	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

CM4620 Injectable Emulsion Versus Supportive Care in Patients With Acute Pancreatitis and SIRS

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Low Dose Group n=8 Participants Consisted of 8 patients, 5 female and 3 male, who were randomized to receive CM4620-IE 1.0 mg/kg on Days 1 and 1.4 mg/kg on Days 2-4. All doses of CM4620-IE were administered intravenously (IV) over 4 hours.	High Dose Group n=6 Participants Consisted of 6 male patients were randomized to receive CM4620-IE 2.08 mg/kg on Days 1 and 2, and 1.6 mg/kg on Days 3-4. All doses of CM4620-IE will be administered intravenously (IV) over 4 hours.	Standard of Care Group n=7 Participants Consisted of 7 patients, 4 female and 3 male, who received local standard of care.	Total n=21 Participants Total of all reporting groups
Age, Continuous	50.9 years STANDARD_DEVIATION 14.7 • n=5 Participants	44.3 years STANDARD_DEVIATION 7.1 • n=7 Participants	54.9 years STANDARD_DEVIATION 10.7 • n=5 Participants	48.1 years STANDARD_DEVIATION 12.1 • n=4 Participants
Sex: Female, Male Female	5 Participants n=5 Participants	0 Participants n=7 Participants	4 Participants n=5 Participants	9 Participants n=4 Participants
Sex: Female, Male Male	3 Participants n=5 Participants	6 Participants n=7 Participants	3 Participants n=5 Participants	12 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	2 Participants n=7 Participants	0 Participants n=5 Participants	2 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	8 Participants n=5 Participants	4 Participants n=7 Participants	7 Participants n=5 Participants	19 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 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	0 Participants n=4 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants	6 Participants n=4 Participants
Race (NIH/OMB) White	6 Participants n=5 Participants	4 Participants n=7 Participants	4 Participants n=5 Participants	14 Participants n=4 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Region of Enrollment United States	8 participants n=5 Participants	6 participants n=7 Participants	7 participants n=5 Participants	21 participants n=4 Participants

PRIMARY outcome

Timeframe: 90 Days

Safety and tolerability will be assessed by monitoring the frequency, duration and severity of treatment-emergent adverse events (TEAEs) throughout the study period.

Outcome measures

Outcome measures
Measure	Low Dose Group + SC n=8 Participants Consisted of 8 patients, 5 female and 3 male, who were randomized to receive CM4620-IE 1.0 mg/kg on Days 1 and 1.4 mg/kg on Days 2-4. All doses of CM4620-IE were administered intravenously (IV) over 4 hours. All patients were also to receive standard of care (SC).	High Dose Group + SC n=6 Participants Consisted of 6 male patients were randomized to receive CM4620-IE 2.08 mg/kg on Days 1 and 2, and 1.6 mg/kg on Days 3-4. All doses of CM4620-IE will be administered intravenously (IV) over 4 hours. All patients were also to receive standard of care (SC).	Standard of Care Group (SC) n=7 Participants Consisted of 7 patients, 4 female and 3 male, who received local standard of care.
The Safety and Tolerability of CM4620-IE in Patients With Acute Pancreatitis and Accompanying Systemic Inflammatory Response Syndrome (SIRS) or Hypoxemia. TEAEs leading to discontinuation	0 Participants	2 Participants	0 Participants
The Safety and Tolerability of CM4620-IE in Patients With Acute Pancreatitis and Accompanying Systemic Inflammatory Response Syndrome (SIRS) or Hypoxemia. TEAE patients	7 Participants	5 Participants	3 Participants
The Safety and Tolerability of CM4620-IE in Patients With Acute Pancreatitis and Accompanying Systemic Inflammatory Response Syndrome (SIRS) or Hypoxemia. Severe TEAE patients	0 Participants	2 Participants	2 Participants
The Safety and Tolerability of CM4620-IE in Patients With Acute Pancreatitis and Accompanying Systemic Inflammatory Response Syndrome (SIRS) or Hypoxemia. SAE patients	2 Participants	1 Participants	2 Participants
The Safety and Tolerability of CM4620-IE in Patients With Acute Pancreatitis and Accompanying Systemic Inflammatory Response Syndrome (SIRS) or Hypoxemia. TEAEs leading to death	0 Participants	1 Participants	0 Participants
The Safety and Tolerability of CM4620-IE in Patients With Acute Pancreatitis and Accompanying Systemic Inflammatory Response Syndrome (SIRS) or Hypoxemia. Treatment-related TEAEs	0 Participants	1 Participants	0 Participants

SECONDARY outcome

Timeframe: 5 days (or discharge, if earlier)

Population: One patient treated with the high dose regimen+SC did not receive a CTSI score at either the Screening or Day 5 or Discharge CECTs. One patient treated with SC alone did not receive a CTSI score at Screening because contrast was not given.

CTSI score measures abnormal pancreatic morphology and is the sum of two subscales. The Balthazar subscale rates pancreatic CT image findings on a scale of 0 (normal) to 4 (2 or more peri-pancreatic fluid collections. The Pancreatic Necrosis subscale rates pancreatic necrosis from 0 (none) to 6 (\>50%). The two subscales are summed for a CTSI score of 0-3 (mild AP), 4-6 (moderate AP), and 7-10 (severe AP).

Outcome measures

Outcome measures
Measure	Low Dose Group + SC n=8 Participants Consisted of 8 patients, 5 female and 3 male, who were randomized to receive CM4620-IE 1.0 mg/kg on Days 1 and 1.4 mg/kg on Days 2-4. All doses of CM4620-IE were administered intravenously (IV) over 4 hours. All patients were also to receive standard of care (SC).	High Dose Group + SC n=5 Participants Consisted of 6 male patients were randomized to receive CM4620-IE 2.08 mg/kg on Days 1 and 2, and 1.6 mg/kg on Days 3-4. All doses of CM4620-IE will be administered intravenously (IV) over 4 hours. All patients were also to receive standard of care (SC).	Standard of Care Group (SC) n=7 Participants Consisted of 7 patients, 4 female and 3 male, who received local standard of care.
The Number of Patients With a Change in Computed Tomography Severity Index (CTSI) Score Between Screening and Day 5 (or Discharge, if Earlier) Screening · Number of Patients with Mild AP	4 Participants	1 Participants	2 Participants
The Number of Patients With a Change in Computed Tomography Severity Index (CTSI) Score Between Screening and Day 5 (or Discharge, if Earlier) Screening · Number of Patients with Moderate AP	4 Participants	4 Participants	3 Participants
The Number of Patients With a Change in Computed Tomography Severity Index (CTSI) Score Between Screening and Day 5 (or Discharge, if Earlier) Screening · Number of Patients with Severe AP	0 Participants	0 Participants	1 Participants
The Number of Patients With a Change in Computed Tomography Severity Index (CTSI) Score Between Screening and Day 5 (or Discharge, if Earlier) Day 5 or Discharge, if earlier · Number of Patients with Mild AP	7 Participants	1 Participants	3 Participants
The Number of Patients With a Change in Computed Tomography Severity Index (CTSI) Score Between Screening and Day 5 (or Discharge, if Earlier) Day 5 or Discharge, if earlier · Number of Patients with Moderate AP	1 Participants	4 Participants	3 Participants
The Number of Patients With a Change in Computed Tomography Severity Index (CTSI) Score Between Screening and Day 5 (or Discharge, if Earlier) Day 5 or Discharge, if earlier · Number of Patients with Severe AP	0 Participants	0 Participants	1 Participants

SECONDARY outcome

Timeframe: at 72 hours (or discharge, if earlier)

Defined as eating ≥ 50% of a solid meal without vomiting or an increase in pain

Outcome measures

Outcome measures
Measure	Low Dose Group + SC n=8 Participants Consisted of 8 patients, 5 female and 3 male, who were randomized to receive CM4620-IE 1.0 mg/kg on Days 1 and 1.4 mg/kg on Days 2-4. All doses of CM4620-IE were administered intravenously (IV) over 4 hours. All patients were also to receive standard of care (SC).	High Dose Group + SC n=6 Participants Consisted of 6 male patients were randomized to receive CM4620-IE 2.08 mg/kg on Days 1 and 2, and 1.6 mg/kg on Days 3-4. All doses of CM4620-IE will be administered intravenously (IV) over 4 hours. All patients were also to receive standard of care (SC).	Standard of Care Group (SC) n=7 Participants Consisted of 7 patients, 4 female and 3 male, who received local standard of care.
The Number of Patients Tolerating Solid Food	5 number of patients tolerating solid food	2 number of patients tolerating solid food	1 number of patients tolerating solid food

SECONDARY outcome

Timeframe: at Day 10 (or discharge, if earlier)

Defined as eating ≥ 50% of a solid meal without vomiting or an increase in pain

Outcome measures

Outcome measures
Measure	Low Dose Group + SC n=8 Participants Consisted of 8 patients, 5 female and 3 male, who were randomized to receive CM4620-IE 1.0 mg/kg on Days 1 and 1.4 mg/kg on Days 2-4. All doses of CM4620-IE were administered intravenously (IV) over 4 hours. All patients were also to receive standard of care (SC).	High Dose Group + SC n=6 Participants Consisted of 6 male patients were randomized to receive CM4620-IE 2.08 mg/kg on Days 1 and 2, and 1.6 mg/kg on Days 3-4. All doses of CM4620-IE will be administered intravenously (IV) over 4 hours. All patients were also to receive standard of care (SC).	Standard of Care Group (SC) n=7 Participants Consisted of 7 patients, 4 female and 3 male, who received local standard of care.
The Number of Patients Tolerating Solid Food	8 number of patients tolerating solid food	5 number of patients tolerating solid food	3 number of patients tolerating solid food

SECONDARY outcome

Timeframe: ≥ 48 hours

The presence of SIRS was defined as the presence of at least 2 of the following 4 criteria: * Temperature \< 36°C or \> 38°C; * Heart rate \> 90 beats/minute; * Respiratory rate \> 20 breaths/minute or arterial carbon dioxide tension (PaCO2) \< 32 mmHg; * White blood cell count (WBC) \> 12,000 cells/mm3 or \< 4,000 cells/mm3 or \> 10% immature (band) forms. * The SIRS score was determined at Screening, prior to randomization, and every 12 hours until Day 6, after which it was determined every 24 hours.

Outcome measures

Outcome measures
Measure	Low Dose Group + SC n=8 Participants Consisted of 8 patients, 5 female and 3 male, who were randomized to receive CM4620-IE 1.0 mg/kg on Days 1 and 1.4 mg/kg on Days 2-4. All doses of CM4620-IE were administered intravenously (IV) over 4 hours. All patients were also to receive standard of care (SC).	High Dose Group + SC n=6 Participants Consisted of 6 male patients were randomized to receive CM4620-IE 2.08 mg/kg on Days 1 and 2, and 1.6 mg/kg on Days 3-4. All doses of CM4620-IE will be administered intravenously (IV) over 4 hours. All patients were also to receive standard of care (SC).	Standard of Care Group (SC) n=7 Participants Consisted of 7 patients, 4 female and 3 male, who received local standard of care.
Percentage of Patients With Persistent Systemic Inflammatory Response Syndrome (SIRS)	1 Participants	4 Participants	5 Participants

SECONDARY outcome

Timeframe: Day 10 (or discharge, if earlier)

Population: Only patients with a maximum IL-6 value ≥ 150 pg/mL in the first 24 hours were analyzed. Further, since some patients IL-6 values decreased below 150 pg/mL, they are not displayed in the results table. Analysis only included patients who still had IL-6 values ≥ 150 pg/mL at Day 10 or discharge (whichever was earlier).

Assess blood serum samples to be analyzed for interleuken (IL-6) llevels pg/mL collected in the first 24 hours and daily thereafter. Samples were sent to the central laboratory. The results were not provided to the Principal Investigator or treating physician.

Outcome measures

Outcome measures
Measure	Low Dose Group + SC n=4 Participants Consisted of 8 patients, 5 female and 3 male, who were randomized to receive CM4620-IE 1.0 mg/kg on Days 1 and 1.4 mg/kg on Days 2-4. All doses of CM4620-IE were administered intravenously (IV) over 4 hours. All patients were also to receive standard of care (SC).	High Dose Group + SC n=3 Participants Consisted of 6 male patients were randomized to receive CM4620-IE 2.08 mg/kg on Days 1 and 2, and 1.6 mg/kg on Days 3-4. All doses of CM4620-IE will be administered intravenously (IV) over 4 hours. All patients were also to receive standard of care (SC).	Standard of Care Group (SC) n=3 Participants Consisted of 7 patients, 4 female and 3 male, who received local standard of care.
IL-6 Values in Patients With a Maximum IL-6 Value ≥ 150 pg/mL in the First 24 Hours Admission IL-6 Levels · IL-6 ≥ 1000 pg/mL	0 Participants	2 Participants	0 Participants
IL-6 Values in Patients With a Maximum IL-6 Value ≥ 150 pg/mL in the First 24 Hours Admission IL-6 Levels · 150 pg/mL ≤ IL-6 < 1000 pg/mL	4 Participants	1 Participants	3 Participants
IL-6 Values in Patients With a Maximum IL-6 Value ≥ 150 pg/mL in the First 24 Hours Day 10 or discharge IL-6 Levels · IL-6 ≥ 1000 pg/mL	0 Participants	0 Participants	0 Participants
IL-6 Values in Patients With a Maximum IL-6 Value ≥ 150 pg/mL in the First 24 Hours Day 10 or discharge IL-6 Levels · 150 pg/mL ≤ IL-6 < 1000 pg/mL	0 Participants	1 Participants	2 Participants

SECONDARY outcome

Timeframe: discharge

Length of stay in hospital in days (randomization to discharge)

Outcome measures

Outcome measures
Measure	Low Dose Group + SC n=8 Participants Consisted of 8 patients, 5 female and 3 male, who were randomized to receive CM4620-IE 1.0 mg/kg on Days 1 and 1.4 mg/kg on Days 2-4. All doses of CM4620-IE were administered intravenously (IV) over 4 hours. All patients were also to receive standard of care (SC).	High Dose Group + SC n=6 Participants Consisted of 6 male patients were randomized to receive CM4620-IE 2.08 mg/kg on Days 1 and 2, and 1.6 mg/kg on Days 3-4. All doses of CM4620-IE will be administered intravenously (IV) over 4 hours. All patients were also to receive standard of care (SC).	Standard of Care Group (SC) n=7 Participants Consisted of 7 patients, 4 female and 3 male, who received local standard of care.
Median Days in Hospital	3.06 days Interval 1.5 to 8.2	6.97 days Interval 1.8 to 18.3	6.02 days Interval 1.1 to 30.0

Adverse Events

Low Dose Group

Serious events: 2 serious events

Other events: 7 other events

Deaths: 0 deaths

High Dose Group

Serious events: 1 serious events

Other events: 5 other events

Deaths: 1 deaths

Standard of Care Group

Serious events: 2 serious events

Other events: 3 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Low Dose Group n=8 participants at risk Consisted of 8 patients, 5 female and 3 male, who were randomized to receive CM4620-IE 1.0 mg/kg on Days 1 and 1.4 mg/kg on Days 2-4. All doses of CM4620-IE were administered intravenously (IV) over 4 hours.	High Dose Group n=6 participants at risk Consisted of 6 male patients were randomized to receive CM4620-IE 2.08 mg/kg on Days 1 and 2, and 1.6 mg/kg on Days 3-4. All doses of CM4620-IE will be administered intravenously (IV) over 4 hours.	Standard of Care Group n=7 participants at risk Consisted of 7 patients, 4 female and 3 male, who received local standard of care.
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.00% 0/8 • Adverse event data were collected over 90 days after randomization.	16.7% 1/6 • Number of events 1 • Adverse event data were collected over 90 days after randomization.	14.3% 1/7 • Number of events 1 • Adverse event data were collected over 90 days after randomization.
Renal and urinary disorders Cystitis Non-infective	12.5% 1/8 • Number of events 1 • Adverse event data were collected over 90 days after randomization.	0.00% 0/6 • Adverse event data were collected over 90 days after randomization.	0.00% 0/7 • Adverse event data were collected over 90 days after randomization.
Gastrointestinal disorders Pancreatitis Acute	12.5% 1/8 • Number of events 2 • Adverse event data were collected over 90 days after randomization.	0.00% 0/6 • Adverse event data were collected over 90 days after randomization.	0.00% 0/7 • Adverse event data were collected over 90 days after randomization.
Infections and infestations Sepsis	0.00% 0/8 • Adverse event data were collected over 90 days after randomization.	16.7% 1/6 • Number of events 1 • Adverse event data were collected over 90 days after randomization.	0.00% 0/7 • Adverse event data were collected over 90 days after randomization.
Respiratory, thoracic and mediastinal disorders Acute Respiratory Distress Syndrome	0.00% 0/8 • Adverse event data were collected over 90 days after randomization.	16.7% 1/6 • Number of events 2 • Adverse event data were collected over 90 days after randomization.	0.00% 0/7 • Adverse event data were collected over 90 days after randomization.
Nervous system disorders Hypoxic-Ischemic Encephalopathy	0.00% 0/8 • Adverse event data were collected over 90 days after randomization.	16.7% 1/6 • Number of events 1 • Adverse event data were collected over 90 days after randomization.	0.00% 0/7 • Adverse event data were collected over 90 days after randomization.
Infections and infestations Pneumonia	0.00% 0/8 • Adverse event data were collected over 90 days after randomization.	16.7% 1/6 • Number of events 1 • Adverse event data were collected over 90 days after randomization.	14.3% 1/7 • Number of events 1 • Adverse event data were collected over 90 days after randomization.
Cardiac disorders Pulseless Electrical Activity	0.00% 0/8 • Adverse event data were collected over 90 days after randomization.	16.7% 1/6 • Number of events 1 • Adverse event data were collected over 90 days after randomization.	0.00% 0/7 • Adverse event data were collected over 90 days after randomization.
Nervous system disorders Encephalopathy	0.00% 0/8 • Adverse event data were collected over 90 days after randomization.	0.00% 0/6 • Adverse event data were collected over 90 days after randomization.	14.3% 1/7 • Number of events 1 • Adverse event data were collected over 90 days after randomization.
Respiratory, thoracic and mediastinal disorders Pneumonia Aspiration	0.00% 0/8 • Adverse event data were collected over 90 days after randomization.	0.00% 0/6 • Adverse event data were collected over 90 days after randomization.	14.3% 1/7 • Number of events 1 • Adverse event data were collected over 90 days after randomization.

Other adverse events

Additional Information

Sudarshan Hebbar, MD

CalciMedica, Inc.

Phone: 816-838-7105

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Low Dose Group n=8 participants at risk Consisted of 8 patients, 5 female and 3 male, who were randomized to receive CM4620-IE 1.0 mg/kg on Days 1 and 1.4 mg/kg on Days 2-4. All doses of CM4620-IE were administered intravenously (IV) over 4 hours.	High Dose Group n=6 participants at risk Consisted of 6 male patients were randomized to receive CM4620-IE 2.08 mg/kg on Days 1 and 2, and 1.6 mg/kg on Days 3-4. All doses of CM4620-IE will be administered intravenously (IV) over 4 hours.	Standard of Care Group n=7 participants at risk Consisted of 7 patients, 4 female and 3 male, who received local standard of care.
Metabolism and nutrition disorders Electrolyte imbalance	0.00% 0/8 • Adverse event data were collected over 90 days after randomization.	16.7% 1/6 • Number of events 1 • Adverse event data were collected over 90 days after randomization.	0.00% 0/7 • Adverse event data were collected over 90 days after randomization.
Metabolism and nutrition disorders Fluid Overload	0.00% 0/8 • Adverse event data were collected over 90 days after randomization.	16.7% 1/6 • Number of events 1 • Adverse event data were collected over 90 days after randomization.	14.3% 1/7 • Number of events 1 • Adverse event data were collected over 90 days after randomization.
Metabolism and nutrition disorders Fluid retention	0.00% 0/8 • Adverse event data were collected over 90 days after randomization.	16.7% 1/6 • Number of events 1 • Adverse event data were collected over 90 days after randomization.	0.00% 0/7 • Adverse event data were collected over 90 days after randomization.
Metabolism and nutrition disorders Hyperglycemia	0.00% 0/8 • Adverse event data were collected over 90 days after randomization.	16.7% 1/6 • Number of events 1 • Adverse event data were collected over 90 days after randomization.	0.00% 0/7 • Adverse event data were collected over 90 days after randomization.
Metabolism and nutrition disorders Hypernatremia	0.00% 0/8 • Adverse event data were collected over 90 days after randomization.	0.00% 0/6 • Adverse event data were collected over 90 days after randomization.	14.3% 1/7 • Number of events 1 • Adverse event data were collected over 90 days after randomization.
Metabolism and nutrition disorders Hypokalemia	25.0% 2/8 • Number of events 2 • Adverse event data were collected over 90 days after randomization.	16.7% 1/6 • Number of events 1 • Adverse event data were collected over 90 days after randomization.	0.00% 0/7 • Adverse event data were collected over 90 days after randomization.
Metabolism and nutrition disorders Hypomagnesaemia	12.5% 1/8 • Number of events 1 • Adverse event data were collected over 90 days after randomization.	0.00% 0/6 • Adverse event data were collected over 90 days after randomization.	0.00% 0/7 • Adverse event data were collected over 90 days after randomization.
Metabolism and nutrition disorders Hyponatremia	12.5% 1/8 • Number of events 1 • Adverse event data were collected over 90 days after randomization.	0.00% 0/6 • Adverse event data were collected over 90 days after randomization.	0.00% 0/7 • Adverse event data were collected over 90 days after randomization.
Metabolism and nutrition disorders Hypophosphatemia	12.5% 1/8 • Number of events 1 • Adverse event data were collected over 90 days after randomization.	16.7% 1/6 • Number of events 1 • Adverse event data were collected over 90 days after randomization.	0.00% 0/7 • Adverse event data were collected over 90 days after randomization.
Metabolism and nutrition disorders Malnutrition	0.00% 0/8 • Adverse event data were collected over 90 days after randomization.	33.3% 2/6 • Number of events 2 • Adverse event data were collected over 90 days after randomization.	0.00% 0/7 • Adverse event data were collected over 90 days after randomization.
Metabolism and nutrition disorders Vitamin D Deficiency	0.00% 0/8 • Adverse event data were collected over 90 days after randomization.	0.00% 0/6 • Adverse event data were collected over 90 days after randomization.	14.3% 1/7 • Number of events 1 • Adverse event data were collected over 90 days after randomization.
Blood and lymphatic system disorders Anemia	0.00% 0/8 • Adverse event data were collected over 90 days after randomization.	16.7% 1/6 • Number of events 1 • Adverse event data were collected over 90 days after randomization.	14.3% 1/7 • Number of events 1 • Adverse event data were collected over 90 days after randomization.
Blood and lymphatic system disorders Leukocytosis	12.5% 1/8 • Number of events 1 • Adverse event data were collected over 90 days after randomization.	16.7% 1/6 • Number of events 1 • Adverse event data were collected over 90 days after randomization.	0.00% 0/7 • Adverse event data were collected over 90 days after randomization.
Blood and lymphatic system disorders Normocytic anemia	0.00% 0/8 • Adverse event data were collected over 90 days after randomization.	16.7% 1/6 • Number of events 1 • Adverse event data were collected over 90 days after randomization.	0.00% 0/7 • Adverse event data were collected over 90 days after randomization.
Blood and lymphatic system disorders Thrombocytopenia	12.5% 1/8 • Number of events 1 • Adverse event data were collected over 90 days after randomization.	16.7% 1/6 • Number of events 1 • Adverse event data were collected over 90 days after randomization.	0.00% 0/7 • Adverse event data were collected over 90 days after randomization.
Blood and lymphatic system disorders Thrombocytosis	0.00% 0/8 • Adverse event data were collected over 90 days after randomization.	16.7% 1/6 • Number of events 1 • Adverse event data were collected over 90 days after randomization.	0.00% 0/7 • Adverse event data were collected over 90 days after randomization.
Gastrointestinal disorders Abdominal Compartment Syndrome	0.00% 0/8 • Adverse event data were collected over 90 days after randomization.	16.7% 1/6 • Number of events 1 • Adverse event data were collected over 90 days after randomization.	0.00% 0/7 • Adverse event data were collected over 90 days after randomization.
Gastrointestinal disorders Abdominal Pain	0.00% 0/8 • Adverse event data were collected over 90 days after randomization.	16.7% 1/6 • Number of events 1 • Adverse event data were collected over 90 days after randomization.	0.00% 0/7 • Adverse event data were collected over 90 days after randomization.
Gastrointestinal disorders Constipation	12.5% 1/8 • Number of events 1 • Adverse event data were collected over 90 days after randomization.	16.7% 1/6 • Number of events 1 • Adverse event data were collected over 90 days after randomization.	0.00% 0/7 • Adverse event data were collected over 90 days after randomization.
Gastrointestinal disorders Hematemesis	0.00% 0/8 • Adverse event data were collected over 90 days after randomization.	16.7% 1/6 • Number of events 1 • Adverse event data were collected over 90 days after randomization.	0.00% 0/7 • Adverse event data were collected over 90 days after randomization.
Gastrointestinal disorders Ileus	0.00% 0/8 • Adverse event data were collected over 90 days after randomization.	16.7% 1/6 • Number of events 1 • Adverse event data were collected over 90 days after randomization.	0.00% 0/7 • Adverse event data were collected over 90 days after randomization.
Gastrointestinal disorders Pancreatic cyst	0.00% 0/8 • Adverse event data were collected over 90 days after randomization.	16.7% 1/6 • Number of events 1 • Adverse event data were collected over 90 days after randomization.	0.00% 0/7 • Adverse event data were collected over 90 days after randomization.
Gastrointestinal disorders Pancreatic necrosis	0.00% 0/8 • Adverse event data were collected over 90 days after randomization.	0.00% 0/6 • Adverse event data were collected over 90 days after randomization.	14.3% 1/7 • Number of events 1 • Adverse event data were collected over 90 days after randomization.
Nervous system disorders Dizziness	12.5% 1/8 • Number of events 1 • Adverse event data were collected over 90 days after randomization.	16.7% 1/6 • Number of events 1 • Adverse event data were collected over 90 days after randomization.	0.00% 0/7 • Adverse event data were collected over 90 days after randomization.
Nervous system disorders Headache	25.0% 2/8 • Number of events 2 • Adverse event data were collected over 90 days after randomization.	16.7% 1/6 • Number of events 1 • Adverse event data were collected over 90 days after randomization.	0.00% 0/7 • Adverse event data were collected over 90 days after randomization.
Psychiatric disorders Alcohol withdrawal syndrome	12.5% 1/8 • Number of events 1 • Adverse event data were collected over 90 days after randomization.	0.00% 0/6 • Adverse event data were collected over 90 days after randomization.	0.00% 0/7 • Adverse event data were collected over 90 days after randomization.
Psychiatric disorders Confusional state	0.00% 0/8 • Adverse event data were collected over 90 days after randomization.	33.3% 2/6 • Number of events 2 • Adverse event data were collected over 90 days after randomization.	14.3% 1/7 • Number of events 1 • Adverse event data were collected over 90 days after randomization.
Psychiatric disorders Delirium	0.00% 0/8 • Adverse event data were collected over 90 days after randomization.	16.7% 1/6 • Number of events 1 • Adverse event data were collected over 90 days after randomization.	0.00% 0/7 • Adverse event data were collected over 90 days after randomization.
Respiratory, thoracic and mediastinal disorders Apnea	12.5% 1/8 • Number of events 1 • Adverse event data were collected over 90 days after randomization.	0.00% 0/6 • Adverse event data were collected over 90 days after randomization.	0.00% 0/7 • Adverse event data were collected over 90 days after randomization.
Renal and urinary disorders Acute Kidney Injury	0.00% 0/8 • Adverse event data were collected over 90 days after randomization.	16.7% 1/6 • Number of events 1 • Adverse event data were collected over 90 days after randomization.	0.00% 0/7 • Adverse event data were collected over 90 days after randomization.
Renal and urinary disorders Chromaturia	0.00% 0/8 • Adverse event data were collected over 90 days after randomization.	16.7% 1/6 • Number of events 1 • Adverse event data were collected over 90 days after randomization.	0.00% 0/7 • Adverse event data were collected over 90 days after randomization.
Cardiac disorders Ventricular extra-systoles	0.00% 0/8 • Adverse event data were collected over 90 days after randomization.	16.7% 1/6 • Number of events 1 • Adverse event data were collected over 90 days after randomization.	0.00% 0/7 • Adverse event data were collected over 90 days after randomization.
Cardiac disorders Ventricular tachycardia	0.00% 0/8 • Adverse event data were collected over 90 days after randomization.	16.7% 1/6 • Number of events 1 • Adverse event data were collected over 90 days after randomization.	0.00% 0/7 • Adverse event data were collected over 90 days after randomization.
General disorders Chills	0.00% 0/8 • Adverse event data were collected over 90 days after randomization.	16.7% 1/6 • Number of events 1 • Adverse event data were collected over 90 days after randomization.	0.00% 0/7 • Adverse event data were collected over 90 days after randomization.
General disorders Pyrexia	0.00% 0/8 • Adverse event data were collected over 90 days after randomization.	16.7% 1/6 • Number of events 1 • Adverse event data were collected over 90 days after randomization.	14.3% 1/7 • Number of events 1 • Adverse event data were collected over 90 days after randomization.
Infections and infestations Sepsis	0.00% 0/8 • Adverse event data were collected over 90 days after randomization.	0.00% 0/6 • Adverse event data were collected over 90 days after randomization.	14.3% 1/7 • Number of events 1 • Adverse event data were collected over 90 days after randomization.
Injury, poisoning and procedural complications Procedural Pain	12.5% 1/8 • Number of events 1 • Adverse event data were collected over 90 days after randomization.	0.00% 0/6 • Adverse event data were collected over 90 days after randomization.	0.00% 0/7 • Adverse event data were collected over 90 days after randomization.
Injury, poisoning and procedural complications Tooth fracture	0.00% 0/8 • Adverse event data were collected over 90 days after randomization.	16.7% 1/6 • Number of events 1 • Adverse event data were collected over 90 days after randomization.	0.00% 0/7 • Adverse event data were collected over 90 days after randomization.
Skin and subcutaneous tissue disorders Hyperhidrosis	12.5% 1/8 • Number of events 1 • Adverse event data were collected over 90 days after randomization.	0.00% 0/6 • Adverse event data were collected over 90 days after randomization.	0.00% 0/7 • Adverse event data were collected over 90 days after randomization.
Skin and subcutaneous tissue disorders Rash	0.00% 0/8 • Adverse event data were collected over 90 days after randomization.	16.7% 1/6 • Number of events 1 • Adverse event data were collected over 90 days after randomization.	0.00% 0/7 • Adverse event data were collected over 90 days after randomization.
Hepatobiliary disorders Biliary dilation	0.00% 0/8 • Adverse event data were collected over 90 days after randomization.	16.7% 1/6 • Number of events 1 • Adverse event data were collected over 90 days after randomization.	0.00% 0/7 • Adverse event data were collected over 90 days after randomization.
Immune system disorders Hypersensitivity	0.00% 0/8 • Adverse event data were collected over 90 days after randomization.	16.7% 1/6 • Number of events 1 • Adverse event data were collected over 90 days after randomization.	0.00% 0/7 • Adverse event data were collected over 90 days after randomization.
Investigations Transaminases increased	0.00% 0/8 • Adverse event data were collected over 90 days after randomization.	16.7% 1/6 • Number of events 1 • Adverse event data were collected over 90 days after randomization.	0.00% 0/7 • Adverse event data were collected over 90 days after randomization.
Reproductive system and breast disorders Scrotal edema	0.00% 0/8 • Adverse event data were collected over 90 days after randomization.	16.7% 1/6 • Number of events 1 • Adverse event data were collected over 90 days after randomization.	0.00% 0/7 • Adverse event data were collected over 90 days after randomization.