This is a Phase 1, double-blind, placebo-controlled trial in three parts. A single ascending dose (SAD) study in six cohorts receiving a single subcutaneous (SC) dose of 1, 10, 30, 60, 100, or 200 mg of rezafungin; a multiple ascending dose (MAD) study in four cohorts receiving 30 mg x 3 doses, 60 mg x 3 doses, 100 mg x 3 doses, or 200 mg x 3 doses of rezafungin SC with dosing frequency of once every 7 days; and a two-period cross-over bioavailability (BA) study receiving 100 mg of rezafungin. The two period cross-over BA study will be assessed unblinded in two sequences (10 subjects, 100 mg or maximum tolerated dose (MTD) of rezafungin in Part 1); 5 subjects will receive an SC injection of rezafungin in Period 1 followed by an intravenous (IV) infusion of rezafungin in Period 2, and 5 subjects will receive an IV infusion of rezafungin in Period 1 followed by an SC injection of rezafungin in Period 2. Each SAD (except cohort 1) and MAD cohort will contain 8 subjects (6 subjects will receive a SC injection of rezafungin and 2 subjects will receive placebo). Each SAD (except cohort 1) and MAD cohort will be conducted with sentinel dosing. SAD cohort 1 will be comprised of 4 subjects (3:1 rezafungin to placebo) with no sentinel dosing. Parts 2 and 3 of the study will only be conducted after FDA review for safety data and PK data from all subjects participating in Part 1; Part 3 may be run in parallel with the first cohort (Cohort 7) of Part 2. Individuals in the SAD cohorts will participate for approximately 58 days, including up to 28 days for screening and 30 days for dosing and follow-up (FU). Individuals in the MAD cohorts will participate for approximately 73 days, including up to 28 days for screening and 45 days for dosing and FU. Individuals in the BA cohorts will participate for approximately 80 days, including up to 28 days for screening and 52 days for dosing and FU. The study will have a duration of approximately 30 months. The primary objectives are to determine the: 1) safety and tolerability of single ascending SC doses (SAD) of rezafungin; 2) safety and tolerability of multiple ascending SC doses (MAD) of rezafungin; and 3) pharmacokinetic (PK) profile in plasma of rezafungin in healthy adult subjects.
This is a Phase 1, double-blind, placebo-controlled trial in three parts. A single ascending dose (SAD) study in six cohorts receiving a single subcutaneous (SC) dose of 1, 10, 30, 60, 100, or 200 mg of rezafungin; a multiple ascending dose (MAD) study in four cohorts receiving 30 mg x 3 doses, 60 mg x 3 doses, 100 mg x 3 doses, or 200 mg x 3 doses of rezafungin SC with dosing frequency of once every 7 days; and a two-period cross-over bioavailability (BA) study receiving 100 mg of rezafungin. The two period cross-over BA study will be assessed unblinded in two sequences (10 subjects, 100 mg or maximum tolerated dose (MTD) of rezafungin in Part 1); 5 subjects will receive an SC injection of rezafungin in Period 1 followed by an intravenous (IV) infusion of rezafungin in Period 2, and 5 subjects will receive an IV infusion of rezafungin in Period 1 followed by an SC injection of rezafungin in Period 2. Each SAD (except cohort 1) and MAD cohort will contain 8 subjects (6 subjects will receive a SC injection of rezafungin and 2 subjects will receive placebo). Each SAD (except cohort 1) and MAD cohort will be conducted with sentinel dosing. SAD cohort 1 will be comprised of 4 subjects (3:1 rezafungin to placebo) with no sentinel dosing. Parts 2 and 3 of the study will only be conducted after FDA review for safety data and PK data from all subjects participating in Part 1; Part 3 may be run in parallel with the first cohort (Cohort 7) of Part 2. Individuals in the SAD cohorts will participate for approximately 58 days, including up to 28 days for screening and 30 days for dosing and follow-up (FU). Individuals in the MAD cohorts will participate for approximately 73 days, including up to 28 days for screening and 45 days for dosing and FU. Individuals in the BA cohorts will participate for approximately 80 days, including up to 28 days for screening and 52 days for dosing and FU. The study will have a duration of approximately 30 months. The primary objectives are to determine the: 1) safety and tolerability of single ascending SC doses (SAD) of rezafungin; 2) safety and tolerability of multiple ascending SC doses (MAD) of rezafungin; and 3) pharmacokinetic (PK) profile in plasma of rezafungin in healthy adult subjects. The secondary objective is to evaluate the BA of rezafungin when administered by SC injection relative to IV infusion in healthy adult subjects.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
DOUBLE
Enrollment
14
5% Dextrose Injection, USP, a sterile, nonpyrogenic solution of dextrose in water for injection. The solution has the osmolarity of 252 mOsmol/L, which is slightly hypotonic. This solution contains no bacteriostat, antimicrobial agent or added buffer.
Rezafungin, 100 mg/mL, is a sterile liquid product supplied in single-dose vials containing 1.0 mL of extractable volume. The active pharmaceutical ingredient is rezafungin acetate, a water-soluble amorphous acetate salt. The inactive ingredient is mannitol.
Rezafungin, 200 mg/vial, is a sterile product supplied as a white to pale yellow lyophilized powder in single-dose glass vials for reconstitution with Sterile Water for Injection, United States Pharmacopeia (USP). The reconstituted product is diluted in 0.9% Sodium Chloride Injection, USP for IV infusion. The active pharmaceutical ingredient is rezafungin acetate, a water-soluble amorphous acetate salt. The inactive ingredients include excipients of mannitol, polysorbate 80, and histidine.
ICON Early Phase Services Clinical Research Unit
San Antonio, Texas, United States
Number of Participants With Abnormal Chemistry Laboratory Toxicity Results for Single Ascending Dose (SAD) on Day 2
Laboratory parameters and associated thresholds include albumin \<=3.4 g/dL, glucose \<= 69 mg/dL or \>=106 mg/dL, blood urea nitrogen (BUN) \>= 21 mg/dL, potassium \>=5.2 mEq/L or \<=3.4 mEq/L, calcium \< 8.7 mg/dL or \>=10.3 mg/dL, sodium \<=132 mEq/L or \>=144 mEq/L, total protein \<=5.9 g/dL, creatinine \>=1.3 mg/dL (male) or \>= 1.0 mg/dL (female), creatine phosphokinase \>= 309 U/L, phosphorus \<=2.4 mg/dL, alkaline phosphatase \>= 131 IU/L (males) or \>= 106 IU/L (female), aspartate aminotransferase \>= 40 U/L (male) or \>= 32 U/L (female), alanine aminotransferase \>=41 U/L (male) or \>= 33 U/L (female), and total bilirubin \>=106 mg/dL. If a clinical chemistry laboratory value met the threshold for an AE at baseline, subsequent safety laboratory results were only considered to be an AE if the grading worsened in severity.
Time frame: Day 2
Number of Participants With Abnormal Chemistry Laboratory Toxicity Results for Single Ascending Dose (SAD) on Day 7
Laboratory parameters and associated thresholds include albumin \<=3.4 g/dL, glucose \<= 69 mg/dL or \>=106 mg/dL, blood urea nitrogen (BUN) \>= 21 mg/dL, potassium \>=5.2 mEq/L or \<=3.4 mEq/L, calcium \< 8.7 mg/dL or \>=10.3 mg/dL, sodium \<=132 mEq/L or \>=144 mEq/L, total protein \<=5.9 g/dL, creatinine \>=1.3 mg/dL (male) or \>= 1.0 mg/dL (female), creatine phosphokinase \>= 309 U/L, phosphorus \<=2.4 mg/dL, alkaline phosphatase \>= 131 IU/L (males) or \>= 106 IU/L (female), aspartate aminotransferase \>= 40 U/L (male) or \>= 32 U/L (female), alanine aminotransferase \>=41 U/L (male) or \>= 33 U/L (female), and total bilirubin \>=106 mg/dL. If a clinical chemistry laboratory value met the threshold for an AE at baseline, subsequent safety laboratory results were only considered to be an AE if the grading worsened in severity.
Time frame: Day 7
Number of Participants With Abnormal Chemistry Laboratory Toxicity Results for Single Ascending Dose (SAD) on Day 30
Laboratory parameters and associated thresholds include albumin \<=3.4 g/dL, glucose \<= 69 mg/dL or \>=106 mg/dL, blood urea nitrogen (BUN) \>= 21 mg/dL, potassium \>=5.2 mEq/L or \<=3.4 mEq/L, calcium \< 8.7 mg/dL or \>=10.3 mg/dL, sodium \<=132 mEq/L or \>=144 mEq/L, total protein \<=5.9 g/dL, creatinine \>=1.3 mg/dL (male) or \>= 1.0 mg/dL (female), creatine phosphokinase \>= 309 U/L, phosphorus \<=2.4 mg/dL, alkaline phosphatase \>= 131 IU/L (males) or \>= 106 IU/L (female), aspartate aminotransferase \>= 40 U/L (male) or \>= 32 U/L (female), alanine aminotransferase \>=41 U/L (male) or \>= 33 U/L (female), and total bilirubin \>=106 mg/dL. If a clinical chemistry laboratory value met the threshold for an AE at baseline, subsequent safety laboratory results were only considered to be an AE if the grading worsened in severity.
Time frame: Day 30
Number of Participants With Abnormal Chemistry Laboratory Toxicity Results for Multiple Ascending Dose (MAD)
Laboratory parameters and associated thresholds include albumin \<=3.4 g/dL, glucose \<= 69 mg/dL or \>=106 mg/dL, blood urea nitrogen (BUN) \>= 21 mg/dL, potassium \>=5.2 mEq/L or \<=3.4 mEq/L, calcium \< 8.7 mg/dL or \>=10.3 mg/dL, sodium \<=132 mEq/L or \>=144 mEq/L, total protein \<=5.9 g/dL, creatinine \>=1.3 mg/dL (male) or \>= 1.0 mg/dL (female), creatine phosphokinase \>= 309 U/L, phosphorus \<=2.4 mg/dL, alkaline phosphatase \>= 131 IU/L (males) or \>= 106 IU/L (female), aspartate aminotransferase \>= 40 U/L (male) or \>= 32 U/L (female), alanine aminotransferase \>=41 U/L (male) or \>= 33 U/L (female), and total bilirubin \>=106 mg/dL. If a clinical chemistry laboratory value met the threshold for an AE at baseline, subsequent safety laboratory results were only considered to be an AE if the grading worsened in severity.
Time frame: Day 2 through Day 45
Number of Participants With Abnormal Hematology Laboratory Toxicity Results for Single Ascending Dose (SAD) on Day 2
Laboratory parameters and associated thresholds for adverse events include hemoglobin \<= 12.2 g/dL (male) or \<= 10.8 g/dL (female), hematocrit \<= 36.1 % (male) or \<= 32.6 % (female), red blood cell (RBC) count \<= 4.1 x 10\^6/uL (male) or \<= 3.7 x 10\^6/uL (female), white blood cell (WBC) count \>= 9,001 cell/mm3 or \<= 2,499 cell/mm3 (African American Males) or \>= 11,001 cell/mm3 or \<= 2,499 cell/mm3 (African American Females) or \>= 10,001 cell/mm3 or \<= 3,999 cell/mm3 (all others), neutrophil count \<= 1,299 cell/mm3 (African Americans) or \<= 1,699 cell/mm3 (all others), lymphocyte count \<= 799 cell/mm3, monocyte count \>= 1001 cell/mm3, eosinophil count \>= 871 cell/mm3, basophil count \>= 101 cell/mm3, and platelet count \<= 149 x 10\^3/mm3. If a result met the threshold for an AE at baseline, subsequent results were only considered to be an AE if the grading worsened in severity.
Time frame: Day 2
Number of Participants With Abnormal Hematology Laboratory Toxicity Results for Single Ascending Dose (SAD) on Day 7
Laboratory parameters and associated thresholds for adverse events include hemoglobin \<= 12.2 g/dL (male) or \<= 10.8 g/dL (female), hematocrit \<= 36.1 % (male) or \<= 32.6 % (female), red blood cell (RBC) count \<= 4.1 x 10\^6/uL (male) or \<= 3.7 x 10\^6/uL (female), white blood cell (WBC) count \>= 9,001 cell/mm3 or \<= 2,499 cell/mm3 (African American Males) or \>= 11,001 cell/mm3 or \<= 2,499 cell/mm3 (African American Females) or \>= 10,001 cell/mm3 or \<= 3,999 cell/mm3 (all others), neutrophil count \<= 1,299 cell/mm3 (African Americans) or \<= 1,699 cell/mm3 (all others), lymphocyte count \<= 799 cell/mm3, monocyte count \>= 1001 cell/mm3, eosinophil count \>= 871 cell/mm3, basophil count \>= 101 cell/mm3, and platelet count \<= 149 x 10\^3/mm3. If a result met the threshold for an AE at baseline, subsequent results were only considered to be an AE if the grading worsened in severity.
Time frame: Day 7
Number of Participants With Abnormal Hematology Laboratory Toxicity Results for Single Ascending Dose (SAD) on Day 30
Laboratory parameters and associated thresholds for adverse events include hemoglobin \<= 12.2 g/dL (male) or \<= 10.8 g/dL (female), hematocrit \<= 36.1 % (male) or \<= 32.6 % (female), red blood cell (RBC) count \<= 4.1 x 10\^6/uL (male) or \<= 3.7 x 10\^6/uL (female), white blood cell (WBC) count \>= 9,001 cell/mm3 or \<= 2,499 cell/mm3 (African American Males) or \>= 11,001 cell/mm3 or \<= 2,499 cell/mm3 (African American Females) or \>= 10,001 cell/mm3 or \<= 3,999 cell/mm3 (all others), neutrophil count \<= 1,299 cell/mm3 (African Americans) or \<= 1,699 cell/mm3 (all others), lymphocyte count \<= 799 cell/mm3, monocyte count \>= 1001 cell/mm3, eosinophil count \>= 871 cell/mm3, basophil count \>= 101 cell/mm3, and platelet count \<= 149 x 10\^3/mm3. If a result met the threshold for an AE at baseline, subsequent results were only considered to be an AE if the grading worsened in severity.
Time frame: Day 30
Number of Participants With Abnormal Hematology Laboratory Toxicity Results for Multiple Ascending Dose (MAD)
Laboratory parameters and associated thresholds for adverse events include hemoglobin \<= 12.2 g/dL (male) or \<= 10.8 g/dL (female), hematocrit \<= 36.1 % (male) or \<= 32.6 % (female), red blood cell (RBC) count \<= 4.1 x 10\^6/uL (male) or \<= 3.7 x 10\^6/uL (female), white blood cell (WBC) count \>= 9,001 cell/mm3 or \<= 2,499 cell/mm3 (African American Males) or \>= 11,001 cell/mm3 or \<= 2,499 cell/mm3 (African American Females) or \>= 10,001 cell/mm3 or \<= 3,999 cell/mm3 (all others), neutrophil count \<= 1,299 cell/mm3 (African Americans) or \<= 1,699 cell/mm3 (all others), lymphocyte count \<= 799 cell/mm3, monocyte count \>= 1001 cell/mm3, eosinophil count \>= 871 cell/mm3, basophil count \>= 101 cell/mm3, and platelet count \<= 149 x 10\^3/mm3. If a result met the threshold for an AE at baseline, subsequent results were only considered to be an AE if the grading worsened in severity.
Time frame: Day 2 through Day 45
Number of Participants With Abnormal Coagulation Laboratory Toxicity Results for Single Ascending Dose (SAD), Day 2
Laboratory parameters include prothrombin time (PT), activated partial prothrombin time (PTT), and prothrombin international normalized ratio (INR). Thresholds for adverse events were considered as PT \>= 11.1 s (before 23DEC2019) or \>= 11.6 s (on or after 23DEC2019), PTT \>= 34.1 s (before 23DEC2019) or \>= 30.1 (on or after 23DEC2019), INR \>= 1.2. If a coagulation laboratory value met the threshold for an AE at baseline, subsequent safety laboratory results were only considered to be an AE if the grading worsened in severity.
Time frame: Day 2
Number of Participants With Abnormal Coagulation Laboratory Toxicity Results for Single Ascending Dose (SAD), Day 7
Laboratory parameters include prothrombin time (PT), activated partial prothrombin time (PTT), and prothrombin international normalized ratio (INR). Thresholds for adverse events were considered as PT \>= 11.1 s (before 23DEC2019) or \>= 11.6 s (on or after 23DEC2019), PTT \>= 34.1 s (before 23DEC2019) or \>= 30.1 (on or after 23DEC2019), INR \>= 1.2. If a coagulation laboratory value met the threshold for an AE at baseline, subsequent safety laboratory results were only considered to be an AE if the grading worsened in severity.
Time frame: Day 7
Number of Participants With Abnormal Coagulation Laboratory Toxicity Results for Single Ascending Dose (SAD), Day 30
Laboratory parameters include prothrombin time (PT), activated partial prothrombin time (PTT), and prothrombin international normalized ratio (INR). Thresholds for adverse events were considered as PT \>= 11.1 s (before 23DEC2019) or \>= 11.6 s (on or after 23DEC2019), PTT \>= 34.1 s (before 23DEC2019) or \>= 30.1 (on or after 23DEC2019), INR \>= 1.2. If a coagulation laboratory value met the threshold for an AE at baseline, subsequent safety laboratory results were only considered to be an AE if the grading worsened in severity.
Time frame: Day 30
Number of Participants With Abnormal Coagulation Laboratory Toxicity Results for Multiple Ascending Dose (MAD)
Laboratory parameters include prothrombin time (PT), activated partial prothrombin time (PTT), and prothrombin international normalized ratio (INR). Thresholds for adverse events were considered as PT \>= 11.1 s (before 23DEC2019) or \>= 11.6 s (on or after 23DEC2019), PTT \>= 34.1 s (before 23DEC2019) or \>= 30.1 (on or after 23DEC2019), INR \>= 1.2. If a coagulation laboratory value met the threshold for an AE at baseline, subsequent safety laboratory results were only considered to be an AE if the grading worsened in severity.
Time frame: Day 2 through Day 45
Number of Participants With Abnormal Urinalysis Laboratory Toxicity Results for Single Ascending Dose (SAD), Day 2
Laboratory parameters include protein, glucose, and occult blood. Thresholds for adverse events were considered as protein \>= 1+, glucose \>= 1+, and occult blood \>= 5 (before 23DEC2019) or \>=3 (on or after 23DEC2019). If a urinalysis laboratory value met the threshold for an AE at baseline, subsequent safety laboratory results were only considered to be an AE if the grading worsened in severity.
Time frame: Day 2
Number of Participants With Abnormal Urinalysis Laboratory Toxicity Results for Single Ascending Dose (SAD), Day 7
Laboratory parameters include protein, glucose, and occult blood. Thresholds for adverse events were considered as protein \>= 1+, glucose \>= 1+, and occult blood \>= 5 (before 23DEC2019) or \>=3 (on or after 23DEC2019). If a urinalysis laboratory value met the threshold for an AE at baseline, subsequent safety laboratory results were only considered to be an AE if the grading worsened in severity.
Time frame: Day 7
Number of Participants With Abnormal Urinalysis Laboratory Toxicity Results for Single Ascending Dose (SAD), Day 30
Laboratory parameters include protein, glucose, and occult blood. Thresholds for adverse events were considered as protein \>= 1+, glucose \>= 1+, and occult blood \>= 5 (before 23DEC2019) or \>=3 (on or after 23DEC2019). If a urinalysis laboratory value met the threshold for an AE at baseline, subsequent safety laboratory results were only considered to be an AE if the grading worsened in severity.
Time frame: Day 30
Number of Participants With Abnormal Urinalysis Laboratory Toxicity Results for Multiple Ascending Dose (MAD)
Each subject is only counted once per toxicity grade for the worst severity recorded. Laboratory parameters include protein, glucose, and occult blood. Thresholds for adverse events were considered as protein \>= 1+, glucose \>= 1+, and occult blood \>= 5 (before 23DEC2019) or \>=3 (on or after 23DEC2019). If a urinalysis laboratory value met the threshold for an AE at baseline, subsequent safety laboratory results were only considered to be an AE if the grading worsened in severity.
Time frame: Day 2 through Day 45
Number of Participants With Abnormal ECG Toxicity Results for Single Ascending Dose (SAD), Day 1
Each subject is only counted once per toxicity grade for the worst severity recorded. ECG parameters include PR interval and QTcF interval. Thresholds for adverse events were considered as PR interval \>= 0.21 sec, a type II 2nd degree AV block, or ventricular pause \>3 sec and QTcF interval \>= 450 msec or \>= 30 msec above baseline. If an ECG value met the threshold for an AE at baseline, subsequent safety ECG results were only considered to be an AE if the grading worsened in severity.
Time frame: Day 1
Number of Participants With Abnormal ECG Toxicity Results for Single Ascending Dose (SAD), Day 7
Each subject is only counted once per toxicity grade for the worst severity recorded. ECG parameters include PR interval and QTcF interval. Thresholds for adverse events were considered as PR interval \>= 0.21 sec, a type II 2nd degree AV block, or ventricular pause \>3 sec and QTcF interval \>= 450 msec or \>= 30 msec above baseline. If an ECG value met the threshold for an AE at baseline, subsequent safety ECG results were only considered to be an AE if the grading worsened in severity.
Time frame: Day 7
Number of Participants With Abnormal ECG Toxicity Results for Single Ascending Dose (SAD), Day 30
Each subject is only counted once per toxicity grade for the worst severity recorded. ECG parameters include PR interval and QTcF interval. Thresholds for adverse events were considered as PR interval \>= 0.21 sec, a type II 2nd degree AV block, or ventricular pause \>3 sec and QTcF interval \>= 450 msec or \>= 30 msec above baseline. If an ECG value met the threshold for an AE at baseline, subsequent safety ECG results were only considered to be an AE if the grading worsened in severity.
Time frame: Day 30
Number of Participants With Abnormal ECG Toxicity Results for Multiple Ascending Doses (MAD)
This table includes the maximum severity experienced over all post-baseline time points. ECG parameters include PR interval and QTcF interval. Thresholds for adverse events were considered as PR interval \>= 0.21 sec, a type II 2nd degree AV block, or ventricular pause \>3 sec and QTcF interval \>= 450 msec or \>= 30 msec above baseline. If an ECG value met the threshold for an AE at baseline, subsequent safety ECG results were only considered to be an AE if the grading worsened in severity.
Time frame: Day 1 through Day 45
Number of Participants With Abnormal Physical Exams for Single Ascending Dose (SAD), Day 1
Physical examination includes general appearance; head, eyes, nose and throat; neck; chest and lungs; cardiovascular system, abdomen, musculoskeletal system, lymph nodes, extremities/skin, and neurological system.
Time frame: Day 1
Number of Participants With Abnormal Physical Exams for Single Ascending Dose (SAD), Day 2
Physical examination includes general appearance; head, eyes, nose and throat; neck; chest and lungs; cardiovascular system, abdomen, musculoskeletal system, lymph nodes, extremities/skin, and neurological system.
Time frame: Day 2
Number of Participants With Abnormal Physical Exams for Single Ascending Dose (SAD), Day 4
Physical examination includes general appearance; head, eyes, nose and throat; neck; chest and lungs; cardiovascular system, abdomen, musculoskeletal system, lymph nodes, extremities/skin, and neurological system.
Time frame: Day 4
Number of Participants With Abnormal Physical Exams for Single Ascending Dose (SAD), Day 7
Physical examination includes general appearance; head, eyes, nose and throat; neck; chest and lungs; cardiovascular system, abdomen, musculoskeletal system, lymph nodes, extremities/skin, and neurological system.
Time frame: Day 7
Number of Participants With Abnormal Physical Exams for Single Ascending Dose (SAD), Day 30
Physical examination includes general appearance; head, eyes, nose and throat; neck; chest and lungs; cardiovascular system, abdomen, musculoskeletal system, lymph nodes, extremities/skin, and neurological system.
Time frame: Day 30
Number of Participants With Abnormal Physical Exams for Multiple Ascending Dose (MAD)
Physical examination includes general appearance; head, eyes, nose and throat; neck; chest and lungs; cardiovascular system, abdomen, musculoskeletal system, lymph nodes, extremities/skin, and neurological system.
Time frame: Day 1 through Day 45
Number of Participants With Abnormal Vital Signs for Single Ascending Dose (SAD), Day 1, 15 Minutes Post-dose
Each subject is only counted once per toxicity grade for the worst severity recorded. Vital sign parameters include systolic blood pressure (BP), diastolic BP, heart rate, respiratory rate, and temperature. Thresholds for abnormal vital signs were considered as systolic BP \>= 141 mmHg or \<= 89 mmHg, diastolic BP \>= 91 mmHg, heart rate \<= 54 bpm (baseline \>= 60 bpm) or \<=50 (baseline \< 60 bpm) or \>= 101 bpm, respiratory rate \>= 23 breaths per minute, and temperature \>= 38.0 degrees Celsius. If a vital sign result met the threshold for an AE at baseline, subsequent vital sign results were only considered to be an AE if the grading worsened in severity.
Time frame: Day 1, 15 minutes post-dose
Number of Participants With Abnormal Vital Signs for Single Ascending Dose (SAD), Day 1, 1 Hour Post-dose
Each subject is only counted once per toxicity grade for the worst severity recorded. Vital sign parameters include systolic blood pressure (BP), diastolic BP, heart rate, respiratory rate, and temperature. Thresholds for abnormal vital signs were considered as systolic BP \>= 141 mmHg or \<= 89 mmHg, diastolic BP \>= 91 mmHg, heart rate \<= 54 bpm (baseline \>= 60 bpm) or \<=50 (baseline \< 60 bpm) or \>= 101 bpm, respiratory rate \>= 23 breaths per minute, and temperature \>= 38.0 degrees Celsius. If a vital sign result met the threshold for an AE at baseline, subsequent vital sign results were only considered to be an AE if the grading worsened in severity.
Time frame: Day 1, 1 hour post-dose
Number of Participants With Abnormal Vital Signs for Single Ascending Dose (SAD), Day 1, 2 Hours Post-dose
Each subject is only counted once per toxicity grade for the worst severity recorded. Vital sign parameters include systolic blood pressure (BP), diastolic BP, heart rate, respiratory rate, and temperature. Thresholds for abnormal vital signs were considered as systolic BP \>= 141 mmHg or \<= 89 mmHg, diastolic BP \>= 91 mmHg, heart rate \<= 54 bpm (baseline \>= 60 bpm) or \<=50 (baseline \< 60 bpm) or \>= 101 bpm, respiratory rate \>= 23 breaths per minute, and temperature \>= 38.0 degrees Celsius. If a vital sign result met the threshold for an AE at baseline, subsequent vital sign results were only considered to be an AE if the grading worsened in severity.
Time frame: Day 1, 2 hours post-dose
Number of Participants With Abnormal Vital Signs for Single Ascending Dose (SAD), Day 2
Each subject is only counted once per toxicity grade for the worst severity recorded. Vital sign parameters include systolic blood pressure (BP), diastolic BP, heart rate, respiratory rate, and temperature. Thresholds for abnormal vital signs were considered as systolic BP \>= 141 mmHg or \<= 89 mmHg, diastolic BP \>= 91 mmHg, heart rate \<= 54 bpm (baseline \>= 60 bpm) or \<=50 (baseline \< 60 bpm) or \>= 101 bpm, respiratory rate \>= 23 breaths per minute, and temperature \>= 38.0 degrees Celsius. If a vital sign result met the threshold for an AE at baseline, subsequent vital sign results were only considered to be an AE if the grading worsened in severity.
Time frame: Day 2
Number of Participants With Abnormal Vital Signs for Single Ascending Dose (SAD), Day 4
Each subject is only counted once per toxicity grade for the worst severity recorded. Vital sign parameters include systolic blood pressure (BP), diastolic BP, heart rate, respiratory rate, and temperature. Thresholds for abnormal vital signs were considered as systolic BP \>= 141 mmHg or \<= 89 mmHg, diastolic BP \>= 91 mmHg, heart rate \<= 54 bpm (baseline \>= 60 bpm) or \<=50 (baseline \< 60 bpm) or \>= 101 bpm, respiratory rate \>= 23 breaths per minute, and temperature \>= 38.0 degrees Celsius. If a vital sign result met the threshold for an AE at baseline, subsequent vital sign results were only considered to be an AE if the grading worsened in severity.
Time frame: Day 4
Number of Participants With Abnormal Vital Signs for Single Ascending Dose (SAD), Day 7
Each subject is only counted once per toxicity grade for the worst severity recorded. Vital sign parameters include systolic blood pressure (BP), diastolic BP, heart rate, respiratory rate, and temperature. Thresholds for abnormal vital signs were considered as systolic BP \>= 141 mmHg or \<= 89 mmHg, diastolic BP \>= 91 mmHg, heart rate \<= 54 bpm (baseline \>= 60 bpm) or \<=50 (baseline \< 60 bpm) or \>= 101 bpm, respiratory rate \>= 23 breaths per minute, and temperature \>= 38.0 degrees Celsius. If a vital sign result met the threshold for an AE at baseline, subsequent vital sign results were only considered to be an AE if the grading worsened in severity.
Time frame: Day 7
Number of Participants With Abnormal Vital Signs for Single Ascending Dose (SAD), Day 14
Each subject is only counted once per toxicity grade for the worst severity recorded. Vital sign parameters include systolic blood pressure (BP), diastolic BP, heart rate, respiratory rate, and temperature. Thresholds for abnormal vital signs were considered as systolic BP \>= 141 mmHg or \<= 89 mmHg, diastolic BP \>= 91 mmHg, heart rate \<= 54 bpm (baseline \>= 60 bpm) or \<=50 (baseline \< 60 bpm) or \>= 101 bpm, respiratory rate \>= 23 breaths per minute, and temperature \>= 38.0 degrees Celsius. If a vital sign result met the threshold for an AE at baseline, subsequent vital sign results were only considered to be an AE if the grading worsened in severity.
Time frame: Day 14
Number of Participants With Abnormal Vital Signs for Single Ascending Dose (SAD), Day 30
Each subject is only counted once per toxicity grade for the worst severity recorded. Vital sign parameters include systolic blood pressure (BP), diastolic BP, heart rate, respiratory rate, and temperature. Thresholds for abnormal vital signs were considered as systolic BP \>= 141 mmHg or \<= 89 mmHg, diastolic BP \>= 91 mmHg, heart rate \<= 54 bpm (baseline \>= 60 bpm) or \<=50 (baseline \< 60 bpm) or \>= 101 bpm, respiratory rate \>= 23 breaths per minute, and temperature \>= 38.0 degrees Celsius. If a vital sign result met the threshold for an AE at baseline, subsequent vital sign results were only considered to be an AE if the grading worsened in severity.
Time frame: Day 30
Number of Participants With Abnormal Vital Signs for Multiple Ascending Dose (MAD)
Each subject is only counted once per toxicity grade for the worst severity recorded. Vital sign parameters include systolic blood pressure (BP), diastolic BP, heart rate, respiratory rate, and temperature. Thresholds for abnormal vital signs were considered as systolic BP \>= 141 mmHg or \<= 89 mmHg, diastolic BP \>= 91 mmHg, heart rate \<= 54 bpm (baseline \>= 60 bpm) or \<=50 (baseline \< 60 bpm) or \>= 101 bpm, respiratory rate \>= 23 breaths per minute, and temperature \>= 38.0 degrees Celsius. If a vital sign result met the threshold for an AE at baseline, subsequent vital sign results were only considered to be an AE if the grading worsened in severity.
Time frame: Day 1 through Day 45
Number of Participants With Unsolicited Adverse Events (AEs) for Single Ascending Dose (SAD)
Number of participants with an AE are summarized by MedDRA System Organ Class (SOC) and severity. If a condition was present at screening it was not considered an AE unless the severity worsened.
Time frame: Day 1 through Day 30.
Number of Participants With Unsolicited Adverse Events (AEs) for Multiple Ascending Dose (MAD)
Number of participants with an AE are summarized by MedDRA System Organ Class (SOC). Each subject was counted once per SOC. If a condition was present at screening, it was not considered an AE unless the severity worsened.
Time frame: Day 1 through Day 45
Number of Unsolicited Adverse Events Reported for Single Ascending Dose (SAD)
The total number of unsolicited AE events reported summarized by MedDRA System Organ Class (SOC). If a condition was present at screening it was not considered an AE unless the severity worsened.
Time frame: Day 1 through Day 30.
Number of Unsolicited Adverse Events Reported for Multiple Ascending Dose (MAD)
The total number of unsolicited AE events reported summarized by MedDRA System Organ Class (SOC). If a condition was present at screening it was not considered an AE unless the severity worsened.
Time frame: Day 1 through Day 45
Number of Participants With at Least One Severe Adverse Event (SAE) for Single Ascending Dose (SAD)
The number of participants who reported at least one SAE. SAEs include any AE that resulted in death, a life-threatening event, an inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, or, or a congenital anomaly/birth defect.
Time frame: Day 1 through Day 30
Number of Participants With at Least One Severe Adverse Event (SAE) for Multiple Ascending Dose (MAD)
The number of participants who reported at least one SAE. SAEs include any AE that resulted in death, a life-threatening event, an inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, or, or a congenital anomaly/birth defect.
Time frame: Day 1 through Day 45
Number of Participants With Solicited Local Reactogenicity Symptom(s) for Single Ascending Dose (SAD)
The number of participants who experienced solicited local reactogenicity events (injection site evaluation), summarized by symptom. Specified solicited events include pain, tenderness, pruritus, ecchymosis, erythema, induration, nodule, ulcer, healed, and scar. Thresholds for measurement grades of solicited local reactogenicity events were considered as ecchymosis \>= 25 mm, erythema \>=25 mm, induration \>=25 mm, nodule \>=25 mm, ulcer \>=1 mm. For functional grades of solicited local reactogenicity events, the threshold for tenderness was considered as discomfort only to the touch or worse. For ecchymosis, erythema, induration, nodule, or ulcer thresholds for functional grade was interference with daily activity or worse, or any measurement over 1mm.
Time frame: Day 1 through Day 30
Number of Participants With Solicited Local Reactogenicity Symptom(s) for Multiple Ascending Dose (MAD)
The number of participants who experienced solicited local reactogenicity events (injection site evaluation), summarized by symptom. Specified solicited events include pain, tenderness, pruritus, ecchymosis, erythema, induration, nodule, ulcer, healed, and scar. Thresholds for measurement grades of solicited local reactogenicity events were considered as ecchymosis \>= 25 mm, erythema \>=25 mm, induration \>=25 mm, nodule \>=25 mm, ulcer \>=1 mm. For functional grades of solicited local reactogenicity events, the threshold for tenderness was considered as discomfort only to the touch or worse. For ecchymosis, erythema, induration, nodule, or ulcer thresholds for functional grade was interference with daily activity or worse, or any measurement over 1mm.
Time frame: Day 1 through Day 45
Rezafungin Concentrations in Plasma, SAD 10 mg Dose Group Concentrations of Rezafungin in Plasma Samples
Mean and standard deviation of rezafungin concentrations in plasma from the SAD 10 mg Dose Group by nominal time point (0 h, 0.5 h, 1 h, 2 h, 4 h, 6 h, 8 h, 12 h, 24 h, 48 h, 96 h, 144 h, 312 h, 696 h (post-dose)).
Time frame: 0 h, 0.5 h, 1 h, 2 h, 4 h, 6 h, 8 h, 12 h, 24 h, 48 h, 96 h, 144 h, 312 h, and 696 h post-dose
Rezafungin PK Parameter (Cmax) in Plasma, SAD 10 mg Dose Group
Mean and standard deviation (SD) of the Cmax (ng/mL) PK parameter estimated from the rezafungin plasma concentration-time data.
Time frame: 0 h, 0.5 h, 1 h, 2 h, 4 h, 6 h, 8 h, 12 h, 24 h, 48 h, 96 h, 144 h, 312 h, and 696 h post-dose
Rezafungin PK Parameters (Tmax and t 1/2) in Plasma, SAD 10 mg Dose Group
Mean and standard deviation (SD) of the Tmax (h) and t 1/2 (h) PK parameters were estimated from the rezafungin plasma concentration-time data using Phoenix WinNonlin Non-compartmental Analysis with the following Lambda Z Acceptance Criteria: rsq\_adjusted (adjusted r squared) \>= 0.90, span \>= 3.0 half-lives, and includes at least 3 timepoints after tmax.
Time frame: 0 h, 0.5 h, 1 h, 2 h, 4 h, 6 h, 8 h, 12 h, 24 h, 48 h, 96 h, 144 h, 312 h, and 696 h post-dose
Rezafungin PK Parameters (AUC 0-last and AUC 0-inf ) in Plasma, SAD 10 mg Dose Group
Mean and standard deviation (SD) of the AUC 0-last (h\*ng/mL) and AUC 0-inf (h\*ng/mL) PK parameters were estimated from the rezafungin plasma concentration-time data using Phoenix WinNonlin Non-compartmental Analysis with the following Lambda Z Acceptance Criteria: rsq\_adjusted (adjusted r squared) \>= 0.90, span \>= 3.0 half-lives, and includes at least 3 timepoints after tmax.
Time frame: 0 h, 0.5 h, 1 h, 2 h, 4 h, 6 h, 8 h, 12 h, 24 h, 48 h, 96 h, 144 h, 312 h, and 696 h post-dose
Rezafungin PK Parameter (Lambda z) in Plasma, SAD 10 mg Dose Group
Mean and standard deviation (SD) of the lambda z (1/h) PK parameter was estimated from the rezafungin plasma concentration-time data using Phoenix WinNonlin Non-compartmental Analysis with the following Lambda Z Acceptance Criteria: rsq\_adjusted (adjusted r squared) \>= 0.90, span \>= 3.0 half-lives, and includes at least 3 timepoints after tmax.
Time frame: 0 h, 0.5 h, 1 h, 2 h, 4 h, 6 h, 8 h, 12 h, 24 h, 48 h, 96 h, 144 h, 312 h, and 696 h post-dose
Rezafungin PK Parameter (CL/F) in Plasma, SAD 10 mg Dose Group
Mean and standard deviation (SD) of the CL/F (L/h) PK parameter was estimated from the rezafungin plasma concentration-time data using Phoenix WinNonlin Non-compartmental Analysis with the following Lambda Z Acceptance Criteria: rsq\_adjusted (adjusted r squared) \>= 0.90, span \>= 3.0 half-lives, and includes at least 3 timepoints after tmax.
Time frame: 0 h, 0.5 h, 1 h, 2 h, 4 h, 6 h, 8 h, 12 h, 24 h, 48 h, 96 h, 144 h, 312 h, and 696 h post-dose
Rezafungin PK Parameter (Vz/F) in Plasma, SAD 10 mg Dose Group
Mean and standard deviation (SD) of the Vz/F (L) PK parameter was estimated from the rezafungin plasma concentration-time data using Phoenix WinNonlin Non-compartmental Analysis with the following Lambda Z Acceptance Criteria: rsq\_adjusted (adjusted r squared) \>= 0.90, span \>= 3.0 half-lives, and includes at least 3 timepoints after tmax.
Time frame: 0 h, 0.5 h, 1 h, 2 h, 4 h, 6 h, 8 h, 12 h, 24 h, 48 h, 96 h, 144 h, 312 h, and 696 h post-dose
Rezafungin Concentrations in Plasma Samples, Multiple Ascending Dose (MAD)
Mean and standard deviation of rezafungin concentrations in plasma from the SAD 10 mg Dose Group by nominal time point (0 h, 0.5 h, 1 h, 2 h, 4 h, 6 h, 8 h, and 12 h on Days 1 and 15, 24 h post-dose on Days 2 and 16, 48 h post-dose on Days 3 and 17; at 1 h and 4 h post-dose on Day 8; at 72 h post-dose on Days 4, 11, and 18; at 96 hours post-dose on Days 5, 12, and 19; at 120 h post-dose on Days 6, 13, and 20; at 144 h post-dose on Days 7, 14, and 21; on Days 30 and 45 post-dose)
Time frame: Day 1 through Day 45
Rezafungin PK Parameters in Plasma, Multiple Ascending Dose (MAD)
Mean and standard deviation (SD) of PK parameters estimated from the rezafungin plasma concentration-time data. PK Parameters include Cmax (ng/nL), Tmax (h), AUC 0-last (h\*ng/mL), AUC 0-inf (h\*ng/mL), lambda z (1/h), t 1/2 (h), CL/F (L/h), Vz/F (L).
Time frame: Day 1 through Day 45
Bioavailability (BA) of Rezafungin in BA Cohorts
BA is calculated as the ratio of the area under the curve (AUC) for the subcutaneous (SC) injection to the AUC for the intravenous (IV) infusion, where AUC is assessed by plasma Rezafungin levels. Plasma rezafungin determined by LC-MS/MS methods.
Time frame: Day 1 through Day 52
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