Fungal Infection
Conditions
Keywords
Dose Escalation Study, Double-Blind, Healthy Adult Subjects, Phase 1, Rezafungin, Safety and Pharmacokinetic
Brief summary
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.
Detailed description
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.
Interventions
OTHERPlacebo
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.
DRUGRezafungin
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.
Sponsors
National Institute of Allergy and Infectious Diseases (NIAID)
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
1. Males and females aged 18 to 45 years, inclusive. 2. Willing and able to provide written informed consent and authorization for use of protected health information. 3. Willing and able to comply with protocol requirements, instructions, and protocol-stated restrictions (including confinement to the Clinical Research Unit) and is likely to complete the study as planned. 4. Males must be vasectomized or agree to use barrier contraception (condom with spermicide) from first dose of study drug until at least 18 weeks following the last dose of study drug. 5. Males must agree to refrain from sperm donation from first dose of investigational product (IP) through at least 18 weeks after last dose of IP. 6. Females are eligible if they are of non-childbearing potential\* or if they use a highly effective\*\* method of contraception for 30 days prior to dosing and for a minimum of 30 days after dosing. \*Non-childbearing potential is defined as: Pre-menopausal with documentation of irreversible surgical sterilization (i.e., hysterectomy, bilateral oophorectomy, or bilateral salpingectomy (but not tubal ligation alone); or, Post-menopausal defined as amenorrhea for at least 12 months following cessation of all exogenous hormonal treatments and with Follicle Stimulating Hormone (FSH) levels \> / = 40 mIU/mL at Screening. \*\*A highly effective contraceptive method is, defined by \< 1 percent failure rate that is not affected by user adherence, include surgical sterilization and long-acting reversible contraception (LARC). LARC comes in three forms: progestin-releasing subdermal implants (Nexplanon and Implanon \[Merck\]); copper intrauterine devices (IUD) (ParaGard \[Teva\]); and levonorgestrel-releasing IUDs (Mirena \[Bayer\], Skyla \[Bayer\], and Liletta \[Allergan/Medicines360\]. Subjects must use one of these three methods. 7. Subject is in good health as deemed by the Investigator\*,\*\*. * Good health is defined by the absence of any medical condition described in the
Exclusion criteria
in a subject who undergoes a medical history, with a normal complete physical examination including resting vital signs, and screening safety laboratory testing. * If the subject has an active, ongoing medical condition, the condition cannot meet any of the following criteria: 1) first diagnosed within 3 months of enrollment; 2) is worsening in terms of clinical outcome in last 6 months; or 3) involves need for medication that may pose a risk to subject's safety or significantly impede assessment of adverse events if they participate in the study. 8. Subjects with a body mass index (BMI) (weight in kg divided by height in m, squared) between 18.5 and/or 35.0 kg/m\^2, inclusive, and a minimum weight of 50 kg. 9. Subjects must refrain from strenuous physical activity that could cause muscle aches or injury, including contact sports, at any time from screening until completion of the trial. 10. Subjects must refrain from over-the-counter and prescription medications\* and nutritional supplements within 14 days before first study drug administration, and until after the final study visit. \*Except for hormonal contraceptives, acetaminophen, or ibuprofen. 11. Subject has adequate venous access for blood collection.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Rezafungin PK Parameters in Plasma, Multiple Ascending Dose (MAD) | Day 1 through Day 45 | 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). |
| Number of Participants With Abnormal Physical Exams for Single Ascending Dose (SAD), Day 4 | 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. |
| Number of Participants With Abnormal Chemistry Laboratory Toxicity Results for Single Ascending Dose (SAD) on Day 2 | 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. |
| Number of Participants With Abnormal Physical Exams for Single Ascending Dose (SAD), Day 7 | 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. |
| Number of Participants With Abnormal Chemistry Laboratory Toxicity Results for Single Ascending Dose (SAD) on Day 7 | 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. |
| Number of Participants With Abnormal Chemistry Laboratory Toxicity Results for Single Ascending Dose (SAD) on Day 30 | 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. |
| Number of Participants With Abnormal Chemistry Laboratory Toxicity Results for Multiple Ascending Dose (MAD) | Day 2 through Day 45 | 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. |
| Number of Participants With Abnormal Hematology Laboratory Toxicity Results for Single Ascending Dose (SAD) on Day 2 | 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. |
| Number of Participants With Abnormal Hematology Laboratory Toxicity Results for Single Ascending Dose (SAD) on Day 7 | 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. |
| Number of Participants With Abnormal Hematology Laboratory Toxicity Results for Single Ascending Dose (SAD) on Day 30 | 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. |
| Number of Participants With Abnormal Hematology Laboratory Toxicity Results for Multiple Ascending Dose (MAD) | Day 2 through Day 45 | 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. |
| Number of Participants With Abnormal Coagulation Laboratory Toxicity Results for Single Ascending Dose (SAD), Day 2 | 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. |
| Number of Participants With Abnormal Coagulation Laboratory Toxicity Results for Single Ascending Dose (SAD), Day 7 | 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. |
| Number of Participants With Abnormal Coagulation Laboratory Toxicity Results for Single Ascending Dose (SAD), Day 30 | 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. |
| Number of Participants With Abnormal Coagulation Laboratory Toxicity Results for Multiple Ascending Dose (MAD) | Day 2 through Day 45 | 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. |
| Number of Participants With Abnormal Urinalysis Laboratory Toxicity Results for Single Ascending Dose (SAD), Day 2 | 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. |
| Number of Participants With Abnormal Urinalysis Laboratory Toxicity Results for Single Ascending Dose (SAD), Day 7 | 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. |
| Number of Participants With Abnormal Urinalysis Laboratory Toxicity Results for Single Ascending Dose (SAD), Day 30 | 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. |
| Number of Participants With Abnormal Urinalysis Laboratory Toxicity Results for Multiple Ascending Dose (MAD) | Day 2 through Day 45 | 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. |
| Number of Participants With Abnormal ECG Toxicity Results for Single Ascending Dose (SAD), Day 1 | 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. |
| Number of Participants With Abnormal ECG Toxicity Results for Single Ascending Dose (SAD), Day 7 | 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. |
| Number of Participants With Abnormal ECG Toxicity Results for Single Ascending Dose (SAD), Day 30 | 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. |
| Number of Participants With Abnormal ECG Toxicity Results for Multiple Ascending Doses (MAD) | Day 1 through Day 45 | 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. |
| Number of Participants With Abnormal Physical Exams for Single Ascending Dose (SAD), Day 1 | 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. |
| Number of Participants With Abnormal Physical Exams for Single Ascending Dose (SAD), Day 2 | 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. |
| Number of Participants With Abnormal Physical Exams for Single Ascending Dose (SAD), Day 30 | 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. |
| Number of Participants With Abnormal Physical Exams for Multiple Ascending Dose (MAD) | Day 1 through Day 45 | 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. |
| Number of Participants With Abnormal Vital Signs for Single Ascending Dose (SAD), Day 1, 15 Minutes Post-dose | 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. |
| Number of Participants With Abnormal Vital Signs for Single Ascending Dose (SAD), Day 1, 1 Hour Post-dose | 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. |
| Number of Participants With Abnormal Vital Signs for Single Ascending Dose (SAD), Day 1, 2 Hours Post-dose | 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. |
| Number of Participants With Abnormal Vital Signs for Single Ascending Dose (SAD), Day 2 | 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. |
| Number of Participants With Abnormal Vital Signs for Single Ascending Dose (SAD), Day 4 | 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. |
| Number of Participants With Abnormal Vital Signs for Single Ascending Dose (SAD), Day 7 | 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. |
| Number of Participants With at Least One Severe Adverse Event (SAE) for Single Ascending Dose (SAD) | Day 1 through Day 30 | 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. |
| Number of Participants With Abnormal Vital Signs for Single Ascending Dose (SAD), Day 14 | 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. |
| Number of Participants With Abnormal Vital Signs for Single Ascending Dose (SAD), Day 30 | 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. |
| Number of Participants With Abnormal Vital Signs for Multiple Ascending Dose (MAD) | Day 1 through Day 45 | 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. |
| Number of Participants With Unsolicited Adverse Events (AEs) for Single Ascending Dose (SAD) | Day 1 through Day 30. | 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. |
| Number of Participants With Unsolicited Adverse Events (AEs) for Multiple Ascending Dose (MAD) | Day 1 through Day 45 | 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. |
| Number of Unsolicited Adverse Events Reported for Single Ascending Dose (SAD) | Day 1 through Day 30. | 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. |
| Number of Unsolicited Adverse Events Reported for Multiple Ascending Dose (MAD) | Day 1 through Day 45 | 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. |
| Number of Participants With at Least One Severe Adverse Event (SAE) for Multiple Ascending Dose (MAD) | Day 1 through Day 45 | 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. |
| Number of Participants With Solicited Local Reactogenicity Symptom(s) for Single Ascending Dose (SAD) | Day 1 through Day 30 | 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. |
| Number of Participants With Solicited Local Reactogenicity Symptom(s) for Multiple Ascending Dose (MAD) | Day 1 through Day 45 | 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. |
| Rezafungin Concentrations in Plasma, SAD 10 mg Dose Group Concentrations of Rezafungin in Plasma Samples | 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 | 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)). |
| Rezafungin PK Parameter (Cmax) in Plasma, SAD 10 mg Dose Group | 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 | Mean and standard deviation (SD) of the Cmax (ng/mL) PK parameter estimated from the rezafungin plasma concentration-time data. |
| Rezafungin PK Parameters (Tmax and t 1/2) in Plasma, SAD 10 mg Dose Group | 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 | 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. |
| Rezafungin PK Parameters (AUC 0-last and AUC 0-inf ) in Plasma, SAD 10 mg Dose Group | 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 | 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. |
| Rezafungin PK Parameter (Lambda z) in Plasma, SAD 10 mg Dose Group | 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 | 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. |
| Rezafungin PK Parameter (CL/F) in Plasma, SAD 10 mg Dose Group | 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 | 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. |
| Rezafungin PK Parameter (Vz/F) in Plasma, SAD 10 mg Dose Group | 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 | 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. |
| Rezafungin Concentrations in Plasma Samples, Multiple Ascending Dose (MAD) | Day 1 through Day 45 | 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) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Bioavailability (BA) of Rezafungin in BA Cohorts | Day 1 through Day 52 | 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. |
Countries
United States
Participant flow
Recruitment details
Participants included healthy male and females aged 18-45 years (inclusive). Participants were recruited from the local community to ensure that male, female, and minorities (African American, Native American, Asian, and Hispanics) were represented in the enrolled population. Participants were enrolled between 04DEC2019 and 11MAR2020.
Participants by arm
| Arm | Count |
|---|---|
| SAD1 1 mg (1 injection of 0.1 mL diluted 1:10 in 5% Dextrose Injection, USP) of Rezafungin administered subcutaneously. | 3 |
| SAD2 10 mg (1 injection of 0.1 mL) of Rezafungin administered subcutaneously. | 7 |
| SAD Placebo Placebo participants across all SAD cohorts given matching placebo administered subcutaneously as a single dose in a double-blind manner. | 4 |
| Total | 14 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 | FG010 | FG011 | FG012 | FG013 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Early Termination | 0 | 1 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | SAD1 | Total | SAD Placebo | SAD2 |
|---|---|---|---|---|
| Age, Continuous | 33.7 years STANDARD_DEVIATION 2.1 | 33.6 years STANDARD_DEVIATION 5.7 | 33.8 years STANDARD_DEVIATION 7.5 | 33.6 years STANDARD_DEVIATION 6.5 |
| BMI (kg/m^2) | 27.97 kg/m^2 STANDARD_DEVIATION 1.72 | 27.25 kg/m^2 STANDARD_DEVIATION 3.67 | 25.85 kg/m^2 STANDARD_DEVIATION 4.23 | 27.74 kg/m^2 STANDARD_DEVIATION 4.18 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 7 Participants | 3 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 1 Participants | 7 Participants | 1 Participants | 5 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Height (cm) | 174.73 cm STANDARD_DEVIATION 8.84 | 175.49 cm STANDARD_DEVIATION 6.52 | 172.1 cm STANDARD_DEVIATION 6.15 | 177.74 cm STANDARD_DEVIATION 5.77 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 4 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 2 Participants | 8 Participants | 3 Participants | 3 Participants |
| Sex: Female, Male Female | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Sex: Female, Male Male | 3 Participants | 13 Participants | 4 Participants | 6 Participants |
| Weight (kg) | 85.9 kg STANDARD_DEVIATION 13.75 | 84.54 kg STANDARD_DEVIATION 16.33 | 77.23 kg STANDARD_DEVIATION 18.67 | 88.13 kg STANDARD_DEVIATION 17 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 3 | 0 / 6 | 0 / 3 |
| other Total, other adverse events | 3 / 3 | 6 / 6 | 2 / 3 |
| serious Total, serious adverse events | 0 / 3 | 0 / 6 | 0 / 3 |
Outcome results
Primary
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
Population: The study was terminated on 27APR2020 due to safety concerns. No subjects were enrolled into these groups.
Primary
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
Population: Safety population: All participants that received any amount of study product.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| SAD1 | Number of Participants With Abnormal Chemistry Laboratory Toxicity Results for Single Ascending Dose (SAD) on Day 2 | Alanine Aminotransferase, Increase | 0 Participants |
| SAD1 | Number of Participants With Abnormal Chemistry Laboratory Toxicity Results for Single Ascending Dose (SAD) on Day 2 | Any Parameter | 1 Participants |
| SAD1 | Number of Participants With Abnormal Chemistry Laboratory Toxicity Results for Single Ascending Dose (SAD) on Day 2 | Glucose, Increase | 1 Participants |
| SAD2 | Number of Participants With Abnormal Chemistry Laboratory Toxicity Results for Single Ascending Dose (SAD) on Day 2 | Alanine Aminotransferase, Increase | 1 Participants |
| SAD2 | Number of Participants With Abnormal Chemistry Laboratory Toxicity Results for Single Ascending Dose (SAD) on Day 2 | Any Parameter | 1 Participants |
| SAD2 | Number of Participants With Abnormal Chemistry Laboratory Toxicity Results for Single Ascending Dose (SAD) on Day 2 | Glucose, Increase | 0 Participants |
| SAD Placebo | Number of Participants With Abnormal Chemistry Laboratory Toxicity Results for Single Ascending Dose (SAD) on Day 2 | Any Parameter | 0 Participants |
| SAD Placebo | Number of Participants With Abnormal Chemistry Laboratory Toxicity Results for Single Ascending Dose (SAD) on Day 2 | Glucose, Increase | 0 Participants |
| SAD Placebo | Number of Participants With Abnormal Chemistry Laboratory Toxicity Results for Single Ascending Dose (SAD) on Day 2 | Alanine Aminotransferase, Increase | 0 Participants |
Primary
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
Population: Safety population: All participants that received any amount of study product.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| SAD1 | Number of Participants With Abnormal Chemistry Laboratory Toxicity Results for Single Ascending Dose (SAD) on Day 30 | Any Parameter | 0 Participants |
| SAD1 | Number of Participants With Abnormal Chemistry Laboratory Toxicity Results for Single Ascending Dose (SAD) on Day 30 | Alanine Aminotransferase, Increase | 0 Participants |
| SAD2 | Number of Participants With Abnormal Chemistry Laboratory Toxicity Results for Single Ascending Dose (SAD) on Day 30 | Any Parameter | 3 Participants |
| SAD2 | Number of Participants With Abnormal Chemistry Laboratory Toxicity Results for Single Ascending Dose (SAD) on Day 30 | Alanine Aminotransferase, Increase | 3 Participants |
| SAD Placebo | Number of Participants With Abnormal Chemistry Laboratory Toxicity Results for Single Ascending Dose (SAD) on Day 30 | Any Parameter | 0 Participants |
| SAD Placebo | Number of Participants With Abnormal Chemistry Laboratory Toxicity Results for Single Ascending Dose (SAD) on Day 30 | Alanine Aminotransferase, Increase | 0 Participants |
Primary
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
Population: Safety population: All participants that received any amount of study product.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| SAD1 | Number of Participants With Abnormal Chemistry Laboratory Toxicity Results for Single Ascending Dose (SAD) on Day 7 | Any Parameter | 0 Participants |
| SAD1 | Number of Participants With Abnormal Chemistry Laboratory Toxicity Results for Single Ascending Dose (SAD) on Day 7 | Potassium, Increase | 0 Participants |
| SAD1 | Number of Participants With Abnormal Chemistry Laboratory Toxicity Results for Single Ascending Dose (SAD) on Day 7 | Calcium, Increase | 0 Participants |
| SAD1 | Number of Participants With Abnormal Chemistry Laboratory Toxicity Results for Single Ascending Dose (SAD) on Day 7 | Alanine Aminotransferase, Increase | 0 Participants |
| SAD2 | Number of Participants With Abnormal Chemistry Laboratory Toxicity Results for Single Ascending Dose (SAD) on Day 7 | Alanine Aminotransferase, Increase | 1 Participants |
| SAD2 | Number of Participants With Abnormal Chemistry Laboratory Toxicity Results for Single Ascending Dose (SAD) on Day 7 | Any Parameter | 2 Participants |
| SAD2 | Number of Participants With Abnormal Chemistry Laboratory Toxicity Results for Single Ascending Dose (SAD) on Day 7 | Calcium, Increase | 0 Participants |
| SAD2 | Number of Participants With Abnormal Chemistry Laboratory Toxicity Results for Single Ascending Dose (SAD) on Day 7 | Potassium, Increase | 1 Participants |
| SAD Placebo | Number of Participants With Abnormal Chemistry Laboratory Toxicity Results for Single Ascending Dose (SAD) on Day 7 | Alanine Aminotransferase, Increase | 0 Participants |
| SAD Placebo | Number of Participants With Abnormal Chemistry Laboratory Toxicity Results for Single Ascending Dose (SAD) on Day 7 | Potassium, Increase | 0 Participants |
| SAD Placebo | Number of Participants With Abnormal Chemistry Laboratory Toxicity Results for Single Ascending Dose (SAD) on Day 7 | Calcium, Increase | 1 Participants |
| SAD Placebo | Number of Participants With Abnormal Chemistry Laboratory Toxicity Results for Single Ascending Dose (SAD) on Day 7 | Any Parameter | 1 Participants |
Primary
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
Population: The study was terminated on 27APR2020 due to safety concerns. No subjects were enrolled into these groups.
Primary
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
Population: Safety population: All participants that received any amount of study product.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| SAD1 | Number of Participants With Abnormal Coagulation Laboratory Toxicity Results for Single Ascending Dose (SAD), Day 2 | 0 Participants |
| SAD2 | Number of Participants With Abnormal Coagulation Laboratory Toxicity Results for Single Ascending Dose (SAD), Day 2 | 0 Participants |
| SAD Placebo | Number of Participants With Abnormal Coagulation Laboratory Toxicity Results for Single Ascending Dose (SAD), Day 2 | 0 Participants |
Primary
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
Population: Safety population: All participants that received any amount of study product.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| SAD1 | Number of Participants With Abnormal Coagulation Laboratory Toxicity Results for Single Ascending Dose (SAD), Day 30 | 0 Participants |
| SAD2 | Number of Participants With Abnormal Coagulation Laboratory Toxicity Results for Single Ascending Dose (SAD), Day 30 | 0 Participants |
| SAD Placebo | Number of Participants With Abnormal Coagulation Laboratory Toxicity Results for Single Ascending Dose (SAD), Day 30 | 0 Participants |
Primary
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
Population: Safety population: All participants that received any amount of study product.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| SAD1 | Number of Participants With Abnormal Coagulation Laboratory Toxicity Results for Single Ascending Dose (SAD), Day 7 | 0 Participants |
| SAD2 | Number of Participants With Abnormal Coagulation Laboratory Toxicity Results for Single Ascending Dose (SAD), Day 7 | 0 Participants |
| SAD Placebo | Number of Participants With Abnormal Coagulation Laboratory Toxicity Results for Single Ascending Dose (SAD), Day 7 | 0 Participants |
Primary
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
Population: The study was terminated on 27APR2020 due to safety concerns. No subjects were enrolled into these groups.
Primary
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
Population: Safety population: All participants that received any amount of study product.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| SAD1 | Number of Participants With Abnormal ECG Toxicity Results for Single Ascending Dose (SAD), Day 1 | 0 Participants |
| SAD2 | Number of Participants With Abnormal ECG Toxicity Results for Single Ascending Dose (SAD), Day 1 | 0 Participants |
| SAD Placebo | Number of Participants With Abnormal ECG Toxicity Results for Single Ascending Dose (SAD), Day 1 | 0 Participants |
Primary
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
Population: Safety population: All participants that received any amount of study product.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| SAD1 | Number of Participants With Abnormal ECG Toxicity Results for Single Ascending Dose (SAD), Day 30 | 0 Participants |
| SAD2 | Number of Participants With Abnormal ECG Toxicity Results for Single Ascending Dose (SAD), Day 30 | 0 Participants |
| SAD Placebo | Number of Participants With Abnormal ECG Toxicity Results for Single Ascending Dose (SAD), Day 30 | 0 Participants |
Primary
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
Population: Safety population: All participants that received any amount of study product.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| SAD1 | Number of Participants With Abnormal ECG Toxicity Results for Single Ascending Dose (SAD), Day 7 | 0 Participants |
| SAD2 | Number of Participants With Abnormal ECG Toxicity Results for Single Ascending Dose (SAD), Day 7 | 0 Participants |
| SAD Placebo | Number of Participants With Abnormal ECG Toxicity Results for Single Ascending Dose (SAD), Day 7 | 0 Participants |
Primary
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
Population: The study was terminated on 27APR2020 due to safety concerns. No subjects were enrolled into these groups.
Primary
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
Population: Safety population: All participants that received any amount of study product.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| SAD1 | Number of Participants With Abnormal Hematology Laboratory Toxicity Results for Single Ascending Dose (SAD) on Day 2 | Any Parameter | 1 Participants |
| SAD1 | Number of Participants With Abnormal Hematology Laboratory Toxicity Results for Single Ascending Dose (SAD) on Day 2 | White Blood Cell Count, Decrease | 0 Participants |
| SAD1 | Number of Participants With Abnormal Hematology Laboratory Toxicity Results for Single Ascending Dose (SAD) on Day 2 | White Blood Cell Count, Increase | 0 Participants |
| SAD1 | Number of Participants With Abnormal Hematology Laboratory Toxicity Results for Single Ascending Dose (SAD) on Day 2 | Neutrophil Count, Decrease | 1 Participants |
| SAD1 | Number of Participants With Abnormal Hematology Laboratory Toxicity Results for Single Ascending Dose (SAD) on Day 2 | Monocyte Count, Increase | 0 Participants |
| SAD1 | Number of Participants With Abnormal Hematology Laboratory Toxicity Results for Single Ascending Dose (SAD) on Day 2 | Basophil Count, Increase | 0 Participants |
| SAD2 | Number of Participants With Abnormal Hematology Laboratory Toxicity Results for Single Ascending Dose (SAD) on Day 2 | Basophil Count, Increase | 1 Participants |
| SAD2 | Number of Participants With Abnormal Hematology Laboratory Toxicity Results for Single Ascending Dose (SAD) on Day 2 | Any Parameter | 1 Participants |
| SAD2 | Number of Participants With Abnormal Hematology Laboratory Toxicity Results for Single Ascending Dose (SAD) on Day 2 | Neutrophil Count, Decrease | 0 Participants |
| SAD2 | Number of Participants With Abnormal Hematology Laboratory Toxicity Results for Single Ascending Dose (SAD) on Day 2 | Monocyte Count, Increase | 1 Participants |
| SAD2 | Number of Participants With Abnormal Hematology Laboratory Toxicity Results for Single Ascending Dose (SAD) on Day 2 | White Blood Cell Count, Decrease | 0 Participants |
| SAD2 | Number of Participants With Abnormal Hematology Laboratory Toxicity Results for Single Ascending Dose (SAD) on Day 2 | White Blood Cell Count, Increase | 1 Participants |
| SAD Placebo | Number of Participants With Abnormal Hematology Laboratory Toxicity Results for Single Ascending Dose (SAD) on Day 2 | White Blood Cell Count, Decrease | 1 Participants |
| SAD Placebo | Number of Participants With Abnormal Hematology Laboratory Toxicity Results for Single Ascending Dose (SAD) on Day 2 | White Blood Cell Count, Increase | 0 Participants |
| SAD Placebo | Number of Participants With Abnormal Hematology Laboratory Toxicity Results for Single Ascending Dose (SAD) on Day 2 | Basophil Count, Increase | 0 Participants |
| SAD Placebo | Number of Participants With Abnormal Hematology Laboratory Toxicity Results for Single Ascending Dose (SAD) on Day 2 | Neutrophil Count, Decrease | 0 Participants |
| SAD Placebo | Number of Participants With Abnormal Hematology Laboratory Toxicity Results for Single Ascending Dose (SAD) on Day 2 | Any Parameter | 1 Participants |
| SAD Placebo | Number of Participants With Abnormal Hematology Laboratory Toxicity Results for Single Ascending Dose (SAD) on Day 2 | Monocyte Count, Increase | 0 Participants |
Primary
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
Population: Safety population: All participants that received any amount of study product.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| SAD1 | Number of Participants With Abnormal Hematology Laboratory Toxicity Results for Single Ascending Dose (SAD) on Day 30 | Neutrophil Count, Decrease | 1 Participants |
| SAD1 | Number of Participants With Abnormal Hematology Laboratory Toxicity Results for Single Ascending Dose (SAD) on Day 30 | Any Parameter | 2 Participants |
| SAD1 | Number of Participants With Abnormal Hematology Laboratory Toxicity Results for Single Ascending Dose (SAD) on Day 30 | Eosinophil Count, Increase | 1 Participants |
| SAD2 | Number of Participants With Abnormal Hematology Laboratory Toxicity Results for Single Ascending Dose (SAD) on Day 30 | Neutrophil Count, Decrease | 0 Participants |
| SAD2 | Number of Participants With Abnormal Hematology Laboratory Toxicity Results for Single Ascending Dose (SAD) on Day 30 | Any Parameter | 0 Participants |
| SAD2 | Number of Participants With Abnormal Hematology Laboratory Toxicity Results for Single Ascending Dose (SAD) on Day 30 | Eosinophil Count, Increase | 0 Participants |
| SAD Placebo | Number of Participants With Abnormal Hematology Laboratory Toxicity Results for Single Ascending Dose (SAD) on Day 30 | Any Parameter | 0 Participants |
| SAD Placebo | Number of Participants With Abnormal Hematology Laboratory Toxicity Results for Single Ascending Dose (SAD) on Day 30 | Eosinophil Count, Increase | 0 Participants |
| SAD Placebo | Number of Participants With Abnormal Hematology Laboratory Toxicity Results for Single Ascending Dose (SAD) on Day 30 | Neutrophil Count, Decrease | 0 Participants |
Primary
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
Population: Safety population: All participants that received any amount of study product.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| SAD1 | Number of Participants With Abnormal Hematology Laboratory Toxicity Results for Single Ascending Dose (SAD) on Day 7 | White Blood Cell Count, Decrease | 0 Participants |
| SAD1 | Number of Participants With Abnormal Hematology Laboratory Toxicity Results for Single Ascending Dose (SAD) on Day 7 | Any Parameter | 0 Participants |
| SAD1 | Number of Participants With Abnormal Hematology Laboratory Toxicity Results for Single Ascending Dose (SAD) on Day 7 | White Blood Cell Count, Increase | 0 Participants |
| SAD2 | Number of Participants With Abnormal Hematology Laboratory Toxicity Results for Single Ascending Dose (SAD) on Day 7 | White Blood Cell Count, Decrease | 0 Participants |
| SAD2 | Number of Participants With Abnormal Hematology Laboratory Toxicity Results for Single Ascending Dose (SAD) on Day 7 | Any Parameter | 1 Participants |
| SAD2 | Number of Participants With Abnormal Hematology Laboratory Toxicity Results for Single Ascending Dose (SAD) on Day 7 | White Blood Cell Count, Increase | 1 Participants |
| SAD Placebo | Number of Participants With Abnormal Hematology Laboratory Toxicity Results for Single Ascending Dose (SAD) on Day 7 | Any Parameter | 1 Participants |
| SAD Placebo | Number of Participants With Abnormal Hematology Laboratory Toxicity Results for Single Ascending Dose (SAD) on Day 7 | White Blood Cell Count, Increase | 0 Participants |
| SAD Placebo | Number of Participants With Abnormal Hematology Laboratory Toxicity Results for Single Ascending Dose (SAD) on Day 7 | White Blood Cell Count, Decrease | 1 Participants |
Primary
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
Population: The study was terminated on 27APR2020 due to safety concerns. No subjects were enrolled into these groups.
Primary
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
Population: Safety population: All participants that received any amount of study product.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| SAD1 | Number of Participants With Abnormal Physical Exams for Single Ascending Dose (SAD), Day 1 | Any Parameter | 0 participants |
| SAD1 | Number of Participants With Abnormal Physical Exams for Single Ascending Dose (SAD), Day 1 | Extremities/skin | 0 participants |
| SAD2 | Number of Participants With Abnormal Physical Exams for Single Ascending Dose (SAD), Day 1 | Any Parameter | 1 participants |
| SAD2 | Number of Participants With Abnormal Physical Exams for Single Ascending Dose (SAD), Day 1 | Extremities/skin | 1 participants |
| SAD Placebo | Number of Participants With Abnormal Physical Exams for Single Ascending Dose (SAD), Day 1 | Any Parameter | 0 participants |
| SAD Placebo | Number of Participants With Abnormal Physical Exams for Single Ascending Dose (SAD), Day 1 | Extremities/skin | 0 participants |
Primary
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
Population: Safety population: All participants that received any amount of study product.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| SAD1 | Number of Participants With Abnormal Physical Exams for Single Ascending Dose (SAD), Day 2 | Any Parameter | 0 participants |
| SAD1 | Number of Participants With Abnormal Physical Exams for Single Ascending Dose (SAD), Day 2 | Extremities/skin | 0 participants |
| SAD2 | Number of Participants With Abnormal Physical Exams for Single Ascending Dose (SAD), Day 2 | Extremities/skin | 6 participants |
| SAD2 | Number of Participants With Abnormal Physical Exams for Single Ascending Dose (SAD), Day 2 | Any Parameter | 6 participants |
| SAD Placebo | Number of Participants With Abnormal Physical Exams for Single Ascending Dose (SAD), Day 2 | Extremities/skin | 0 participants |
| SAD Placebo | Number of Participants With Abnormal Physical Exams for Single Ascending Dose (SAD), Day 2 | Any Parameter | 0 participants |
Primary
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
Population: Safety population: All participants that received any amount of study product.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| SAD1 | Number of Participants With Abnormal Physical Exams for Single Ascending Dose (SAD), Day 30 | Any Parameter | 0 participants |
| SAD1 | Number of Participants With Abnormal Physical Exams for Single Ascending Dose (SAD), Day 30 | Extremities/skin | 0 participants |
| SAD2 | Number of Participants With Abnormal Physical Exams for Single Ascending Dose (SAD), Day 30 | Any Parameter | 2 participants |
| SAD2 | Number of Participants With Abnormal Physical Exams for Single Ascending Dose (SAD), Day 30 | Extremities/skin | 2 participants |
| SAD Placebo | Number of Participants With Abnormal Physical Exams for Single Ascending Dose (SAD), Day 30 | Any Parameter | 0 participants |
| SAD Placebo | Number of Participants With Abnormal Physical Exams for Single Ascending Dose (SAD), Day 30 | Extremities/skin | 0 participants |
Primary
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
Population: Safety population: All participants that received any amount of study product.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| SAD1 | Number of Participants With Abnormal Physical Exams for Single Ascending Dose (SAD), Day 4 | Any Parameter | 0 participants |
| SAD1 | Number of Participants With Abnormal Physical Exams for Single Ascending Dose (SAD), Day 4 | Extremities/skin | 0 participants |
| SAD2 | Number of Participants With Abnormal Physical Exams for Single Ascending Dose (SAD), Day 4 | Any Parameter | 5 participants |
| SAD2 | Number of Participants With Abnormal Physical Exams for Single Ascending Dose (SAD), Day 4 | Extremities/skin | 5 participants |
| SAD Placebo | Number of Participants With Abnormal Physical Exams for Single Ascending Dose (SAD), Day 4 | Any Parameter | 0 participants |
| SAD Placebo | Number of Participants With Abnormal Physical Exams for Single Ascending Dose (SAD), Day 4 | Extremities/skin | 0 participants |
Primary
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
Population: Safety population: All participants that received any amount of study product.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| SAD1 | Number of Participants With Abnormal Physical Exams for Single Ascending Dose (SAD), Day 7 | Any Parameter | 0 participants |
| SAD1 | Number of Participants With Abnormal Physical Exams for Single Ascending Dose (SAD), Day 7 | Extremities/skin | 0 participants |
| SAD2 | Number of Participants With Abnormal Physical Exams for Single Ascending Dose (SAD), Day 7 | Any Parameter | 1 participants |
| SAD2 | Number of Participants With Abnormal Physical Exams for Single Ascending Dose (SAD), Day 7 | Extremities/skin | 1 participants |
| SAD Placebo | Number of Participants With Abnormal Physical Exams for Single Ascending Dose (SAD), Day 7 | Extremities/skin | 0 participants |
| SAD Placebo | Number of Participants With Abnormal Physical Exams for Single Ascending Dose (SAD), Day 7 | Any Parameter | 0 participants |
Primary
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
Population: The study was terminated on 27APR2020 due to safety concerns. No subjects were enrolled into these groups.
Primary
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
Population: Safety population: All participants that received any amount of study product.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| SAD1 | Number of Participants With Abnormal Urinalysis Laboratory Toxicity Results for Single Ascending Dose (SAD), Day 2 | 0 Participants |
| SAD2 | Number of Participants With Abnormal Urinalysis Laboratory Toxicity Results for Single Ascending Dose (SAD), Day 2 | 0 Participants |
| SAD Placebo | Number of Participants With Abnormal Urinalysis Laboratory Toxicity Results for Single Ascending Dose (SAD), Day 2 | 0 Participants |
Primary
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
Population: Safety population: All participants that received any amount of study product.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| SAD1 | Number of Participants With Abnormal Urinalysis Laboratory Toxicity Results for Single Ascending Dose (SAD), Day 30 | 0 Participants |
| SAD2 | Number of Participants With Abnormal Urinalysis Laboratory Toxicity Results for Single Ascending Dose (SAD), Day 30 | 0 Participants |
| SAD Placebo | Number of Participants With Abnormal Urinalysis Laboratory Toxicity Results for Single Ascending Dose (SAD), Day 30 | 0 Participants |
Primary
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
Population: Safety population: All participants that received any amount of study product.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| SAD1 | Number of Participants With Abnormal Urinalysis Laboratory Toxicity Results for Single Ascending Dose (SAD), Day 7 | Any Parameter | 0 Participants |
| SAD1 | Number of Participants With Abnormal Urinalysis Laboratory Toxicity Results for Single Ascending Dose (SAD), Day 7 | Protein by Dipstick | 0 Participants |
| SAD2 | Number of Participants With Abnormal Urinalysis Laboratory Toxicity Results for Single Ascending Dose (SAD), Day 7 | Any Parameter | 1 Participants |
| SAD2 | Number of Participants With Abnormal Urinalysis Laboratory Toxicity Results for Single Ascending Dose (SAD), Day 7 | Protein by Dipstick | 1 Participants |
| SAD Placebo | Number of Participants With Abnormal Urinalysis Laboratory Toxicity Results for Single Ascending Dose (SAD), Day 7 | Any Parameter | 0 Participants |
| SAD Placebo | Number of Participants With Abnormal Urinalysis Laboratory Toxicity Results for Single Ascending Dose (SAD), Day 7 | Protein by Dipstick | 0 Participants |
Primary
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
Population: The study was terminated on 27APR2020 due to safety concerns. No subjects were enrolled into this group.
Primary
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
Population: Safety population: All participants that received any amount of study product.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| SAD1 | Number of Participants With Abnormal Vital Signs for Single Ascending Dose (SAD), Day 1, 15 Minutes Post-dose | 0 Participants |
| SAD2 | Number of Participants With Abnormal Vital Signs for Single Ascending Dose (SAD), Day 1, 15 Minutes Post-dose | 0 Participants |
| SAD Placebo | Number of Participants With Abnormal Vital Signs for Single Ascending Dose (SAD), Day 1, 15 Minutes Post-dose | 0 Participants |
Primary
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
Population: Safety population: All participants that received any amount of study product.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| SAD1 | Number of Participants With Abnormal Vital Signs for Single Ascending Dose (SAD), Day 1, 1 Hour Post-dose | Any Parameter | 0 Participants |
| SAD1 | Number of Participants With Abnormal Vital Signs for Single Ascending Dose (SAD), Day 1, 1 Hour Post-dose | Heart Rate, Decrease | 0 Participants |
| SAD2 | Number of Participants With Abnormal Vital Signs for Single Ascending Dose (SAD), Day 1, 1 Hour Post-dose | Any Parameter | 2 Participants |
| SAD2 | Number of Participants With Abnormal Vital Signs for Single Ascending Dose (SAD), Day 1, 1 Hour Post-dose | Heart Rate, Decrease | 2 Participants |
| SAD Placebo | Number of Participants With Abnormal Vital Signs for Single Ascending Dose (SAD), Day 1, 1 Hour Post-dose | Any Parameter | 0 Participants |
| SAD Placebo | Number of Participants With Abnormal Vital Signs for Single Ascending Dose (SAD), Day 1, 1 Hour Post-dose | Heart Rate, Decrease | 0 Participants |
Primary
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
Population: Safety population: All participants that received any amount of study product.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| SAD1 | Number of Participants With Abnormal Vital Signs for Single Ascending Dose (SAD), Day 1, 2 Hours Post-dose | 0 Participants |
| SAD2 | Number of Participants With Abnormal Vital Signs for Single Ascending Dose (SAD), Day 1, 2 Hours Post-dose | 0 Participants |
| SAD Placebo | Number of Participants With Abnormal Vital Signs for Single Ascending Dose (SAD), Day 1, 2 Hours Post-dose | 0 Participants |
Primary
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
Population: Safety population: All participants that received any amount of study product.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| SAD1 | Number of Participants With Abnormal Vital Signs for Single Ascending Dose (SAD), Day 14 | Any Parameter | 1 Participants |
| SAD1 | Number of Participants With Abnormal Vital Signs for Single Ascending Dose (SAD), Day 14 | Heart Rate, Decrease | 1 Participants |
| SAD2 | Number of Participants With Abnormal Vital Signs for Single Ascending Dose (SAD), Day 14 | Any Parameter | 0 Participants |
| SAD2 | Number of Participants With Abnormal Vital Signs for Single Ascending Dose (SAD), Day 14 | Heart Rate, Decrease | 0 Participants |
| SAD Placebo | Number of Participants With Abnormal Vital Signs for Single Ascending Dose (SAD), Day 14 | Any Parameter | 0 Participants |
| SAD Placebo | Number of Participants With Abnormal Vital Signs for Single Ascending Dose (SAD), Day 14 | Heart Rate, Decrease | 0 Participants |
Primary
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
Population: Safety population: All participants that received any amount of study product.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| SAD1 | Number of Participants With Abnormal Vital Signs for Single Ascending Dose (SAD), Day 2 | Any Parameter | 1 Participants |
| SAD1 | Number of Participants With Abnormal Vital Signs for Single Ascending Dose (SAD), Day 2 | Heart Rate, Decrease | 1 Participants |
| SAD2 | Number of Participants With Abnormal Vital Signs for Single Ascending Dose (SAD), Day 2 | Any Parameter | 0 Participants |
| SAD2 | Number of Participants With Abnormal Vital Signs for Single Ascending Dose (SAD), Day 2 | Heart Rate, Decrease | 0 Participants |
| SAD Placebo | Number of Participants With Abnormal Vital Signs for Single Ascending Dose (SAD), Day 2 | Any Parameter | 0 Participants |
| SAD Placebo | Number of Participants With Abnormal Vital Signs for Single Ascending Dose (SAD), Day 2 | Heart Rate, Decrease | 0 Participants |
Primary
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
Population: Safety population: All participants that received any amount of study product.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| SAD1 | Number of Participants With Abnormal Vital Signs for Single Ascending Dose (SAD), Day 30 | Any Parameter | 1 Participants |
| SAD1 | Number of Participants With Abnormal Vital Signs for Single Ascending Dose (SAD), Day 30 | Heart Rate, Decrease | 1 Participants |
| SAD2 | Number of Participants With Abnormal Vital Signs for Single Ascending Dose (SAD), Day 30 | Any Parameter | 0 Participants |
| SAD2 | Number of Participants With Abnormal Vital Signs for Single Ascending Dose (SAD), Day 30 | Heart Rate, Decrease | 0 Participants |
| SAD Placebo | Number of Participants With Abnormal Vital Signs for Single Ascending Dose (SAD), Day 30 | Any Parameter | 0 Participants |
| SAD Placebo | Number of Participants With Abnormal Vital Signs for Single Ascending Dose (SAD), Day 30 | Heart Rate, Decrease | 0 Participants |
Primary
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
Population: Safety population: All participants that received any amount of study product.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| SAD1 | Number of Participants With Abnormal Vital Signs for Single Ascending Dose (SAD), Day 4 | Any Parameter | 1 Participants |
| SAD1 | Number of Participants With Abnormal Vital Signs for Single Ascending Dose (SAD), Day 4 | Heart Rate, Decrease | 1 Participants |
| SAD2 | Number of Participants With Abnormal Vital Signs for Single Ascending Dose (SAD), Day 4 | Any Parameter | 0 Participants |
| SAD2 | Number of Participants With Abnormal Vital Signs for Single Ascending Dose (SAD), Day 4 | Heart Rate, Decrease | 0 Participants |
| SAD Placebo | Number of Participants With Abnormal Vital Signs for Single Ascending Dose (SAD), Day 4 | Any Parameter | 0 Participants |
| SAD Placebo | Number of Participants With Abnormal Vital Signs for Single Ascending Dose (SAD), Day 4 | Heart Rate, Decrease | 0 Participants |
Primary
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
Population: Safety population: All participants that received any amount of study product.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| SAD1 | Number of Participants With Abnormal Vital Signs for Single Ascending Dose (SAD), Day 7 | Any Parameter | 1 Participants |
| SAD1 | Number of Participants With Abnormal Vital Signs for Single Ascending Dose (SAD), Day 7 | Heart Rate, Decrease | 1 Participants |
| SAD2 | Number of Participants With Abnormal Vital Signs for Single Ascending Dose (SAD), Day 7 | Any Parameter | 0 Participants |
| SAD2 | Number of Participants With Abnormal Vital Signs for Single Ascending Dose (SAD), Day 7 | Heart Rate, Decrease | 0 Participants |
| SAD Placebo | Number of Participants With Abnormal Vital Signs for Single Ascending Dose (SAD), Day 7 | Any Parameter | 0 Participants |
| SAD Placebo | Number of Participants With Abnormal Vital Signs for Single Ascending Dose (SAD), Day 7 | Heart Rate, Decrease | 0 Participants |
Primary
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
Population: The study was terminated on 27APR2020 due to safety concerns. No subjects were enrolled into any MAD cohorts.
Primary
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
Population: Safety population: All participants that received any amount of study product.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| SAD1 | Number of Participants With at Least One Severe Adverse Event (SAE) for Single Ascending Dose (SAD) | 0 Participants |
| SAD2 | Number of Participants With at Least One Severe Adverse Event (SAE) for Single Ascending Dose (SAD) | 0 Participants |
| SAD Placebo | Number of Participants With at Least One Severe Adverse Event (SAE) for Single Ascending Dose (SAD) | 0 Participants |
Primary
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
Population: The study was terminated on 27APR2020 due to safety concerns. No subjects were enrolled into this cohort.
Primary
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
Population: Safety population: All participants that received any amount of study product.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| SAD1 | Number of Participants With Solicited Local Reactogenicity Symptom(s) for Single Ascending Dose (SAD) | Any Symptom | 1 Participants |
| SAD1 | Number of Participants With Solicited Local Reactogenicity Symptom(s) for Single Ascending Dose (SAD) | Erythema, Measurement Grade | 0 Participants |
| SAD1 | Number of Participants With Solicited Local Reactogenicity Symptom(s) for Single Ascending Dose (SAD) | Ecchymosis, Measurement Grade | 0 Participants |
| SAD1 | Number of Participants With Solicited Local Reactogenicity Symptom(s) for Single Ascending Dose (SAD) | Ulceration, Functional Grade | 0 Participants |
| SAD1 | Number of Participants With Solicited Local Reactogenicity Symptom(s) for Single Ascending Dose (SAD) | Erythema, Functional Grade | 0 Participants |
| SAD1 | Number of Participants With Solicited Local Reactogenicity Symptom(s) for Single Ascending Dose (SAD) | Induration/Swelling, Functional Grade | 0 Participants |
| SAD1 | Number of Participants With Solicited Local Reactogenicity Symptom(s) for Single Ascending Dose (SAD) | Tenderness | 0 Participants |
| SAD1 | Number of Participants With Solicited Local Reactogenicity Symptom(s) for Single Ascending Dose (SAD) | Induration/Swelling, Measurement Grade | 0 Participants |
| SAD1 | Number of Participants With Solicited Local Reactogenicity Symptom(s) for Single Ascending Dose (SAD) | Ulceration, Measurement Grade | 0 Participants |
| SAD1 | Number of Participants With Solicited Local Reactogenicity Symptom(s) for Single Ascending Dose (SAD) | Nodule, Measurement Grade | 0 Participants |
| SAD1 | Number of Participants With Solicited Local Reactogenicity Symptom(s) for Single Ascending Dose (SAD) | Pruritus | 0 Participants |
| SAD1 | Number of Participants With Solicited Local Reactogenicity Symptom(s) for Single Ascending Dose (SAD) | Pain | 1 Participants |
| SAD1 | Number of Participants With Solicited Local Reactogenicity Symptom(s) for Single Ascending Dose (SAD) | Nodule, Functional Grade | 0 Participants |
| SAD1 | Number of Participants With Solicited Local Reactogenicity Symptom(s) for Single Ascending Dose (SAD) | Ecchymosis, Functional Grade | 0 Participants |
| SAD2 | Number of Participants With Solicited Local Reactogenicity Symptom(s) for Single Ascending Dose (SAD) | Erythema, Functional Grade | 6 Participants |
| SAD2 | Number of Participants With Solicited Local Reactogenicity Symptom(s) for Single Ascending Dose (SAD) | Any Symptom | 6 Participants |
| SAD2 | Number of Participants With Solicited Local Reactogenicity Symptom(s) for Single Ascending Dose (SAD) | Pain | 2 Participants |
| SAD2 | Number of Participants With Solicited Local Reactogenicity Symptom(s) for Single Ascending Dose (SAD) | Tenderness | 4 Participants |
| SAD2 | Number of Participants With Solicited Local Reactogenicity Symptom(s) for Single Ascending Dose (SAD) | Pruritus | 1 Participants |
| SAD2 | Number of Participants With Solicited Local Reactogenicity Symptom(s) for Single Ascending Dose (SAD) | Ecchymosis, Functional Grade | 2 Participants |
| SAD2 | Number of Participants With Solicited Local Reactogenicity Symptom(s) for Single Ascending Dose (SAD) | Ecchymosis, Measurement Grade | 1 Participants |
| SAD2 | Number of Participants With Solicited Local Reactogenicity Symptom(s) for Single Ascending Dose (SAD) | Induration/Swelling, Functional Grade | 1 Participants |
| SAD2 | Number of Participants With Solicited Local Reactogenicity Symptom(s) for Single Ascending Dose (SAD) | Induration/Swelling, Measurement Grade | 1 Participants |
| SAD2 | Number of Participants With Solicited Local Reactogenicity Symptom(s) for Single Ascending Dose (SAD) | Erythema, Measurement Grade | 6 Participants |
| SAD2 | Number of Participants With Solicited Local Reactogenicity Symptom(s) for Single Ascending Dose (SAD) | Nodule, Functional Grade | 5 Participants |
| SAD2 | Number of Participants With Solicited Local Reactogenicity Symptom(s) for Single Ascending Dose (SAD) | Nodule, Measurement Grade | 4 Participants |
| SAD2 | Number of Participants With Solicited Local Reactogenicity Symptom(s) for Single Ascending Dose (SAD) | Ulceration, Functional Grade | 0 Participants |
| SAD2 | Number of Participants With Solicited Local Reactogenicity Symptom(s) for Single Ascending Dose (SAD) | Ulceration, Measurement Grade | 0 Participants |
| SAD Placebo | Number of Participants With Solicited Local Reactogenicity Symptom(s) for Single Ascending Dose (SAD) | Ecchymosis, Functional Grade | 0 Participants |
| SAD Placebo | Number of Participants With Solicited Local Reactogenicity Symptom(s) for Single Ascending Dose (SAD) | Ulceration, Measurement Grade | 0 Participants |
| SAD Placebo | Number of Participants With Solicited Local Reactogenicity Symptom(s) for Single Ascending Dose (SAD) | Erythema, Measurement Grade | 0 Participants |
| SAD Placebo | Number of Participants With Solicited Local Reactogenicity Symptom(s) for Single Ascending Dose (SAD) | Pruritus | 0 Participants |
| SAD Placebo | Number of Participants With Solicited Local Reactogenicity Symptom(s) for Single Ascending Dose (SAD) | Ulceration, Functional Grade | 0 Participants |
| SAD Placebo | Number of Participants With Solicited Local Reactogenicity Symptom(s) for Single Ascending Dose (SAD) | Nodule, Functional Grade | 0 Participants |
| SAD Placebo | Number of Participants With Solicited Local Reactogenicity Symptom(s) for Single Ascending Dose (SAD) | Tenderness | 0 Participants |
| SAD Placebo | Number of Participants With Solicited Local Reactogenicity Symptom(s) for Single Ascending Dose (SAD) | Any Symptom | 0 Participants |
| SAD Placebo | Number of Participants With Solicited Local Reactogenicity Symptom(s) for Single Ascending Dose (SAD) | Induration/Swelling, Functional Grade | 0 Participants |
| SAD Placebo | Number of Participants With Solicited Local Reactogenicity Symptom(s) for Single Ascending Dose (SAD) | Pain | 0 Participants |
| SAD Placebo | Number of Participants With Solicited Local Reactogenicity Symptom(s) for Single Ascending Dose (SAD) | Induration/Swelling, Measurement Grade | 0 Participants |
| SAD Placebo | Number of Participants With Solicited Local Reactogenicity Symptom(s) for Single Ascending Dose (SAD) | Ecchymosis, Measurement Grade | 0 Participants |
| SAD Placebo | Number of Participants With Solicited Local Reactogenicity Symptom(s) for Single Ascending Dose (SAD) | Nodule, Measurement Grade | 0 Participants |
| SAD Placebo | Number of Participants With Solicited Local Reactogenicity Symptom(s) for Single Ascending Dose (SAD) | Erythema, Functional Grade | 0 Participants |
Primary
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
Population: The study was terminated on 27APR2020 due to safety concerns. No subjects were enrolled into any MAD cohorts.
Primary
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.
Population: Safety population: All participants that received any amount of study product.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| SAD1 | Number of Participants With Unsolicited Adverse Events (AEs) for Single Ascending Dose (SAD) | Cardiac disorders | 0 Participants |
| SAD1 | Number of Participants With Unsolicited Adverse Events (AEs) for Single Ascending Dose (SAD) | Investigations | 2 Participants |
| SAD1 | Number of Participants With Unsolicited Adverse Events (AEs) for Single Ascending Dose (SAD) | Any SOC | 3 Participants |
| SAD1 | Number of Participants With Unsolicited Adverse Events (AEs) for Single Ascending Dose (SAD) | General disorders and administration site conditions | 0 Participants |
| SAD2 | Number of Participants With Unsolicited Adverse Events (AEs) for Single Ascending Dose (SAD) | Cardiac disorders | 2 Participants |
| SAD2 | Number of Participants With Unsolicited Adverse Events (AEs) for Single Ascending Dose (SAD) | Any SOC | 6 Participants |
| SAD2 | Number of Participants With Unsolicited Adverse Events (AEs) for Single Ascending Dose (SAD) | Investigations | 5 Participants |
| SAD2 | Number of Participants With Unsolicited Adverse Events (AEs) for Single Ascending Dose (SAD) | General disorders and administration site conditions | 2 Participants |
| SAD Placebo | Number of Participants With Unsolicited Adverse Events (AEs) for Single Ascending Dose (SAD) | Any SOC | 2 Participants |
| SAD Placebo | Number of Participants With Unsolicited Adverse Events (AEs) for Single Ascending Dose (SAD) | Cardiac disorders | 0 Participants |
| SAD Placebo | Number of Participants With Unsolicited Adverse Events (AEs) for Single Ascending Dose (SAD) | General disorders and administration site conditions | 0 Participants |
| SAD Placebo | Number of Participants With Unsolicited Adverse Events (AEs) for Single Ascending Dose (SAD) | Investigations | 2 Participants |
Primary
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
Population: The study was terminated on 27APR2020 due to safety concerns. No subjects were enrolled into any MAD cohorts.
Primary
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.
Population: Safety population: All participants that received any amount of study product.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| SAD1 | Number of Unsolicited Adverse Events Reported for Single Ascending Dose (SAD) | Any SOC | 8 AE events |
| SAD1 | Number of Unsolicited Adverse Events Reported for Single Ascending Dose (SAD) | Investigations | 4 AE events |
| SAD1 | Number of Unsolicited Adverse Events Reported for Single Ascending Dose (SAD) | Cardiac Disorders | 0 AE events |
| SAD1 | Number of Unsolicited Adverse Events Reported for Single Ascending Dose (SAD) | General disorders and administration site conditions | 0 AE events |
| SAD2 | Number of Unsolicited Adverse Events Reported for Single Ascending Dose (SAD) | General disorders and administration site conditions | 2 AE events |
| SAD2 | Number of Unsolicited Adverse Events Reported for Single Ascending Dose (SAD) | Any SOC | 14 AE events |
| SAD2 | Number of Unsolicited Adverse Events Reported for Single Ascending Dose (SAD) | Cardiac Disorders | 2 AE events |
| SAD2 | Number of Unsolicited Adverse Events Reported for Single Ascending Dose (SAD) | Investigations | 8 AE events |
| SAD Placebo | Number of Unsolicited Adverse Events Reported for Single Ascending Dose (SAD) | General disorders and administration site conditions | 0 AE events |
| SAD Placebo | Number of Unsolicited Adverse Events Reported for Single Ascending Dose (SAD) | Investigations | 2 AE events |
| SAD Placebo | Number of Unsolicited Adverse Events Reported for Single Ascending Dose (SAD) | Cardiac Disorders | 0 AE events |
| SAD Placebo | Number of Unsolicited Adverse Events Reported for Single Ascending Dose (SAD) | Any SOC | 2 AE events |
Primary
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
Population: PK Analysis Subset: All participants who completed one full 10 mg rezafungin dose, as randomized and according to cohort; had at least one post-dose plasma sample with a measurable rezafungin concentration from which at least a subset of the designated PK parameters could be determined; and completed the PK part of the trial without any protocol violations that were likely to affect the PK results.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SAD1 | Rezafungin Concentrations in Plasma, SAD 10 mg Dose Group Concentrations of Rezafungin in Plasma Samples | 0 h | 0 ng/mL | Standard Deviation 0 |
| SAD1 | Rezafungin Concentrations in Plasma, SAD 10 mg Dose Group Concentrations of Rezafungin in Plasma Samples | 0.5 h | 0 ng/mL | Standard Deviation 0 |
| SAD1 | Rezafungin Concentrations in Plasma, SAD 10 mg Dose Group Concentrations of Rezafungin in Plasma Samples | 1 h | 0 ng/mL | Standard Deviation 0 |
| SAD1 | Rezafungin Concentrations in Plasma, SAD 10 mg Dose Group Concentrations of Rezafungin in Plasma Samples | 2 h | 8.983 ng/mL | Standard Deviation 7.386 |
| SAD1 | Rezafungin Concentrations in Plasma, SAD 10 mg Dose Group Concentrations of Rezafungin in Plasma Samples | 4 h | 21.5 ng/mL | Standard Deviation 7.954 |
| SAD1 | Rezafungin Concentrations in Plasma, SAD 10 mg Dose Group Concentrations of Rezafungin in Plasma Samples | 6 h | 28.68 ng/mL | Standard Deviation 9.949 |
| SAD1 | Rezafungin Concentrations in Plasma, SAD 10 mg Dose Group Concentrations of Rezafungin in Plasma Samples | 8 h | 36.35 ng/mL | Standard Deviation 13.62 |
| SAD1 | Rezafungin Concentrations in Plasma, SAD 10 mg Dose Group Concentrations of Rezafungin in Plasma Samples | 12 h | 45.9 ng/mL | Standard Deviation 17.56 |
| SAD1 | Rezafungin Concentrations in Plasma, SAD 10 mg Dose Group Concentrations of Rezafungin in Plasma Samples | 24 h | 70.87 ng/mL | Standard Deviation 23.52 |
| SAD1 | Rezafungin Concentrations in Plasma, SAD 10 mg Dose Group Concentrations of Rezafungin in Plasma Samples | 48 h | 97.75 ng/mL | Standard Deviation 27.35 |
| SAD1 | Rezafungin Concentrations in Plasma, SAD 10 mg Dose Group Concentrations of Rezafungin in Plasma Samples | 96 h | 101.8 ng/mL | Standard Deviation 28.3 |
| SAD1 | Rezafungin Concentrations in Plasma, SAD 10 mg Dose Group Concentrations of Rezafungin in Plasma Samples | 144 h | 99.9 ng/mL | Standard Deviation 30.15 |
| SAD1 | Rezafungin Concentrations in Plasma, SAD 10 mg Dose Group Concentrations of Rezafungin in Plasma Samples | 312 h | 49.5 ng/mL | Standard Deviation 15.06 |
| SAD1 | Rezafungin Concentrations in Plasma, SAD 10 mg Dose Group Concentrations of Rezafungin in Plasma Samples | 696 h | 14.52 ng/mL | Standard Deviation 3.594 |
Primary
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
Population: The study was terminated on 27APR2020 due to safety concerns. No subjects were enrolled into any of the MAD cohorts.
Primary
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
Population: PK Analysis Subset: All participants who completed 10 mg rezafungin dose as randomized; had at least one post-dose plasma sample with a measurable rezafungin concentration from which at least a subset of the designated PK parameters could be determined; and completed the PK part of the trial without any protocol violations that were likely to affect the PK results.~CL/F was inestimable for all subjects due to not meeting the specified lambda z acceptance criteria.
Primary
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
Population: PK Analysis Subset: All participants who completed one full 10 mg rezafungin dose, as randomized and according to cohort; had at least one post-dose plasma sample with a measurable rezafungin concentration from which at least a subset of the designated PK parameters could be determined; and completed the PK part of the trial without any protocol violations that were likely to affect the PK results.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| SAD1 | Rezafungin PK Parameter (Cmax) in Plasma, SAD 10 mg Dose Group | 108.3 ng/mL | Standard Deviation 29.5 |
Primary
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
Population: PK Analysis Subset: All participants who completed 10 mg rezafungin dose as randomized; had at least one post-dose plasma sample with a measurable rezafungin concentration from which at least a subset of the designated PK parameters could be determined; and completed the PK part of the trial without any protocol violations that were likely to affect the PK results.~Lambda z was inestimable for all subjects due to not meeting the specified lambda z acceptance criteria.
Primary
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
Population: PK Analysis Subset: All participants who completed 10 mg rezafungin dose as randomized; had at least one post-dose plasma sample with a measurable rezafungin concentration from which at least a subset of the designated PK parameters could be determined; and completed the PK part of the trial without any protocol violations that were likely to affect the PK results.~AUC 0-inf was inestimable for all subjects due to not meeting the specified lambda z acceptance criteria.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SAD1 | Rezafungin PK Parameters (AUC 0-last and AUC 0-inf ) in Plasma, SAD 10 mg Dose Group | AUC 0-last | 33950 h*ng/mL | Standard Deviation 9989 |
Primary
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
Population: The study was terminated on 27APR2020 due to safety concerns. No subjects were enrolled into any of the MAD cohorts.
Primary
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
Population: PK Analysis Subset: All participants who completed 10 mg rezafungin dose as randomized; had at least one post-dose plasma sample with a measurable rezafungin concentration from which at least a subset of the designated PK parameters could be determined; and completed the PK part of the trial without any protocol violations that were likely to affect the PK results.~t 1/2 was inestimable for all subjects due to not meeting the specified lambda z acceptance criteria.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SAD1 | Rezafungin PK Parameters (Tmax and t 1/2) in Plasma, SAD 10 mg Dose Group | Tmax | 120 h | Standard Deviation 40.16 |
Primary
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
Population: PK Analysis Subset: All participants who completed 10 mg rezafungin dose as randomized; had at least one post-dose plasma sample with a measurable rezafungin concentration from which at least a subset of the designated PK parameters could be determined; and completed the PK part of the trial without any protocol violations that were likely to affect the PK results.~Vz/F was inestimable for all subjects due to not meeting the specified lambda z acceptance criteria.
Secondary
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
Population: The study was terminated on 27APR2020 due to safety concerns. No subjects were enrolled into any BA cohort.