Paroxysmal Nocturnal Hemoglobinuria (PNH)
Conditions
Keywords
PNH, Paroxysmal Nocturnal Hemoglobinuria, Complement inhibitor, Anemia, Hemoglobinuria, hematologic diseases, extravascular hemolysis (EVH), intravascular hemolysis (IVH), C3 inhibitor
Brief summary
This study will be the initial exploration of pegcetacoplan in patients with PNH. The assessments of the safety, tolerability, PK, and PD following administration of single and multiples doses of pegcetacoplan will guide decisions to further develop the drug.
Interventions
DRUGPegcetacoplan
Complement (C3) Inhibitor
Sponsors
Apellis Pharmaceuticals, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male or Female * At least 18 years of age * Weigh \>55 kg * Diagnosed with PNH * On treatment with eculizumab (Soliris®) for at least 3 months * Hb \< 10 g/dL at screening OR have received at least one transfusion within 12 months prior to screening * Platelet count of \>30,000/mm3 * Absolute neutrophil count \> 500/mm3 * Women of child-bearing potential (WOCBP) must have a negative pregnancy test at screening and must agree to use protocol defined methods of contraception for the duration of the study (see below) * Males with female partners of child bearing potential must agree to use protocol defined methods of contraception (see below) and agree to refrain from donating sperm for the duration of the study * Willing and able to give informed consent
Exclusion criteria
* Active bacterial infection * Known infection with hepatitis B, C or HIV * Hereditary complement deficiency * History of bone marrow transplantation * Participation in any other investigational drug trial or exposure to other investigational agent, device or procedure within 30 days * Evidence of QTcF prolongation defined as \> 450 ms for males and \> 470 ms for females at screening * Creatinine clearance (CrCl) \< 50 mL/min (Cockcroft-Gault formula) at screening * Breast-feeding women * History of meningococcal disease * No vaccination against N. meningitidis types A, C, W, Y and B (administered as two separate vaccinations), Pneumococcal conjugate vaccine or Pneumococcal polysaccharide vaccine 23 (PCV13 or PPSV23, respectively) and Haemophilus influenzae Type B (Hib) vaccination within 2 years prior to Day 1 (Visit 2) dosing.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects With Treatment-Emergent Adverse Events (TEAEs), Including by Severity, During Single-dose Phase | From single dose of study drug (Day 1) up to 30 days | TEAEs were defined as AEs that developed or worsened after first dose of study drug (Day 1), and up to 30 days after last dose of study drug. The Investigator assessed AEs for severity and relatedness to study drug. AEs were graded according to the Common Terminology Criteria for Adverse Events (CTCAE, v4.03) based on: Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe; Grade 4: Life-threatening; Grade 5: Death related to AE. |
| Number of Subjects With TEAEs, Including by Severity, During Multiple-dose Phase | From first dose of study drug up to 30 days after last dose of study drug (Cohorts 1-3: up to 58 days; Cohort 4: up to 759 days). | TEAEs were defined as AEs that developed or worsened after first dose of study drug (Day 1), and up to 30 days after last dose of study drug. The Investigator assessed AEs for severity and relatedness to study drug. AEs were graded according to CTCAE, v4.03 based on: Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe; Grade 4: Life-threatening; Grade 5: Death related to AE. |
| Area Under the Curve (AUC) From Time 0 to the Last Measurable Concentration (AUC0-t) Over the Multiple Dosing Phase for Cohort 4 | Blood samples for PK assessment were collected pre-dose and 4 hours post dose on Day 1 and pre-dose (trough) on Day 2 and up to Day 785. | Assessment of AUC0-t of pegcetacoplan over the multiple dosing phase, estimated using a non-compartmental approach and calculated by the linear-log trapezoidal method. Pegcetacoplan pharmacokinetic (PK) parameters were summarized for Cohort 4 only. |
| Maximum Pre-dose Serum Concentration (Ctrough,Max) Over the Multiple Dosing Phase for Cohort 4 | Blood samples for PK assessment were collected pre-dose and 4 hours post dose on Day 1 and pre-dose (trough) on Day 2 and up to Day 785. | Assessment of Ctrough,max of pegcetacoplan over the multiple dosing phase, estimated using a non-compartmental approach. Pegcetacoplan PK parameters were summarized for Cohort 4 only. Ctrough,max was calculated for both 270 mg/day and 360 mg/day where subjects received both doses. Note: 1 subject in Cohort 4 who was receiving 360 mg/day was granted Sponsor and institutional review board approval to increase the dose further to the equivalent of 440 mg/day and Ctrough,max is also reported for this dose. |
Countries
United States
Participant flow
Recruitment details
Paroxysmal nocturnal hemoglobinuria (PNH) subjects who were still anemic during treatment with eculizumab (Soliris®) were enrolled in this Phase 1, open-label, single- and multiple-ascending dose study to receive treatment with pegcetacoplan (APL-2) as an add-on to standard of care treatment. The study was conducted at 7 sites in the United States.
Pre-assignment details
Subjects could participate in more than 1 cohort. Overall, 9 unique subjects were evaluated in 4 cohorts, with some subjects participating in \>1 cohort. Single-dose phase: 4 unique subjects evaluated (2 each in Cohorts 1 and 2). Multiple-dose phase: 8 unique subjects evaluated, comprising 3 subjects who also participated in single-dose phase (1 in Cohort 1; 2 in Cohort 2) plus a further 5 unique subjects. Each cohort included a 30-day screening phase prior to treatment with pegcetacoplan.
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1 Single- and Multiple-dose Phase Cohort 1 single-dose phase: Subjects received a single SC dose of 25 mg pegcetacoplan on Day 1.
Cohort 1 multiple-dose phase: Following a waiting period of at least 28 days after single dosing, subjects received 5 mg/day SC dose of pegcetacoplan for 28 days (from Day 29 to Day 56). | 2 |
| Cohort 2 Single- and Multiple-dose Phase Cohort 2 single-dose phase: Subjects received a single SC dose of 50 mg pegcetacoplan on Day 1.
Cohort 2 multiple-dose phase: Following a waiting period of at least 28 days after single dosing, subjects received 30 mg/day SC dose of pegcetacoplan for 28 days (from Day 29 to Day 56). | 1 |
| Cohort 2 Single-dose Phase, Then Cohorts 2, 3, and 4 Multiple-dose Phase Cohort 2 single-dose phase: Subjects received a single SC dose of 50 mg pegcetacoplan on Day 1.
Cohort 2 multiple-dose phase: Following a waiting period of at least 28 days after single dosing, subjects received 30 mg/day SC dose of pegcetacoplan for 28 days (from Day 29 to Day 56).
Cohort 3 multiple-dose phase: Subjects received 180 mg/day SC dose of pegcetacoplan for 28 days (from Day 1 to Day 28).
Cohort 4 multiple-dose phase: Subjects received 270 mg/day SC doses of pegcetacoplan for up to 729 days (from Day 1 up to Day 729). The treatment period consisted of the following:
* Part 1: Subjects received daily doses of pegcetacoplan for 28 days.
* Part 2A: On Day 29, subjects who demonstrated clinical benefit from the treatment were automatically entered into Part 2A and continued to receive daily doses of pegcetacoplan until Day 84.
* Part 2B: If there was ongoing evidence of clinical benefit, subjects who completed Part 2A could enter Part 2B and continue to receive daily doses of pegcetacoplan until Day 364.
* Part 2C: If there was ongoing evidence of clinical benefit, subjects who completed Part 2B could enter Part 2C and continue to receive daily doses of pegcetacoplan until Day 729.
After Day 28 (Part 1), individual subject dose escalation up to a dose of 360 mg/day could occur in subjects who had a sub-optimal hematological response but acceptable tolerability. | 1 |
| Cohorts 3 and 4 Multiple-dose Phase Cohort 3 multiple-dose phase: Subjects received 180 mg/day SC dose of pegcetacoplan for 28 days (from Day 1 to Day 28).
Cohort 4 multiple-dose phase: Subjects received 270 mg/day SC doses of pegcetacoplan for up to 729 days (from Day 1 up to Day 729). The treatment period consisted of the following:
* Part 1: Subjects received daily doses of pegcetacoplan for 28 days.
* Part 2A: On Day 29, subjects who demonstrated clinical benefit from the treatment were automatically entered into Part 2A and continued to receive daily doses of pegcetacoplan until Day 84.
* Part 2B: If there was ongoing evidence of clinical benefit, subjects who completed Part 2A could enter Part 2B and continue to receive daily doses of pegcetacoplan until Day 364.
* Part 2C: If there was ongoing evidence of clinical benefit, subjects who completed Part 2B could enter Part 2C and continue to receive daily doses of pegcetacoplan until Day 729.
After Day 28 (Part 1), individual subject dose escalation up to a dose of 360 mg/day could occur in subjects who had a sub-optimal hematological response but acceptable tolerability. | 1 |
| Cohort 4 Multiple-dose Phase Cohort 4 multiple-dose phase: Subjects received 270 mg/day SC doses of pegcetacoplan for up to 729 days (from Day 1 up to Day 729). The treatment period consisted of the following:
* Part 1: Subjects received daily doses of pegcetacoplan for 28 days.
* Part 2A: On Day 29, subjects who demonstrated clinical benefit from the treatment were automatically entered into Part 2A and continued to receive daily doses of pegcetacoplan until Day 84.
* Part 2B: If there was ongoing evidence of clinical benefit, subjects who completed Part 2A could enter Part 2B and continue to receive daily doses of pegcetacoplan until Day 364.
* Part 2C: If there was ongoing evidence of clinical benefit, subjects who completed Part 2B could enter Part 2C and continue to receive daily doses of pegcetacoplan until Day 729.
After Day 28 (Part 1), individual subject dose escalation up to a dose of 360 mg/day could occur in subjects who had a sub-optimal hematological response but acceptable tolerability. | 4 |
| Total | 9 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Death (after completing single-dose phase) | 1 | 0 | 0 | 0 | 0 |
| Overall Study | Major Intercurrent Illness (during multiple-dose phase) | 0 | 0 | 0 | 0 | 1 |
| Overall Study | Pregnancy (during multiple-dose phase) | 0 | 0 | 1 | 0 | 0 |
| Overall Study | Withdrawal by subject (during multiple-dose phase) | 1 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Cohort 1 Single- and Multiple-dose Phase | Cohort 2 Single- and Multiple-dose Phase | Cohort 2 Single-dose Phase, Then Cohorts 2, 3, and 4 Multiple-dose Phase | Cohorts 3 and 4 Multiple-dose Phase | Cohort 4 Multiple-dose Phase | Total |
|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Age, Categorical Between 18 and 65 years | 1 Participants | 1 Participants | 1 Participants | 1 Participants | 4 Participants | 8 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 2 Participants | 1 Participants | 1 Participants | 0 Participants | 4 Participants | 8 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 2 Participants | 1 Participants | 1 Participants | 1 Participants | 3 Participants | 8 Participants |
| Region of Enrollment United States | 2 participants | 1 participants | 1 participants | 1 participants | 4 participants | 9 participants |
| Sex: Female, Male Female | 2 Participants | 0 Participants | 1 Participants | 1 Participants | 4 Participants | 8 Participants |
| Sex: Female, Male Male | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 2 | 0 / 2 | 0 / 1 | 0 / 2 | 0 / 2 | 0 / 6 |
| other Total, other adverse events | 1 / 2 | 2 / 2 | 1 / 1 | 2 / 2 | 1 / 2 | 6 / 6 |
| serious Total, serious adverse events | 0 / 2 | 0 / 2 | 0 / 1 | 0 / 2 | 0 / 2 | 2 / 6 |
Outcome results
Primary
Area Under the Curve (AUC) From Time 0 to the Last Measurable Concentration (AUC0-t) Over the Multiple Dosing Phase for Cohort 4
Assessment of AUC0-t of pegcetacoplan over the multiple dosing phase, estimated using a non-compartmental approach and calculated by the linear-log trapezoidal method. Pegcetacoplan pharmacokinetic (PK) parameters were summarized for Cohort 4 only.
Time frame: Blood samples for PK assessment were collected pre-dose and 4 hours post dose on Day 1 and pre-dose (trough) on Day 2 and up to Day 785.
Population: The PK population was defined as all subjects in the safety population who had at least 1 PK sample drawn with a measurable serum concentration. Results were reported for Cohort 4 only. Due to the small sample size in Cohorts 1 through 3, summaries for continuous data using descriptive statistics were not performed.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Cohort 1 Single-dose Phase | Area Under the Curve (AUC) From Time 0 to the Last Measurable Concentration (AUC0-t) Over the Multiple Dosing Phase for Cohort 4 | 6,500,000 micrograms*hour/milliliter (μg*hour/mL) |
Primary
Maximum Pre-dose Serum Concentration (Ctrough,Max) Over the Multiple Dosing Phase for Cohort 4
Assessment of Ctrough,max of pegcetacoplan over the multiple dosing phase, estimated using a non-compartmental approach. Pegcetacoplan PK parameters were summarized for Cohort 4 only. Ctrough,max was calculated for both 270 mg/day and 360 mg/day where subjects received both doses. Note: 1 subject in Cohort 4 who was receiving 360 mg/day was granted Sponsor and institutional review board approval to increase the dose further to the equivalent of 440 mg/day and Ctrough,max is also reported for this dose.
Time frame: Blood samples for PK assessment were collected pre-dose and 4 hours post dose on Day 1 and pre-dose (trough) on Day 2 and up to Day 785.
Population: The PK population was defined as all subjects in the safety population who had at least 1 PK sample drawn with a measurable serum concentration. Results were reported for Cohort 4 only. Due to the small sample size in Cohorts 1 through 3, summaries for continuous data using descriptive statistics were not performed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1 Single-dose Phase | Maximum Pre-dose Serum Concentration (Ctrough,Max) Over the Multiple Dosing Phase for Cohort 4 | 270 mg Dose | 627 μg/mL | Standard Deviation 207 |
| Cohort 1 Single-dose Phase | Maximum Pre-dose Serum Concentration (Ctrough,Max) Over the Multiple Dosing Phase for Cohort 4 | 360 mg Dose | 543 μg/mL | Standard Deviation 192 |
| Cohort 1 Single-dose Phase | Maximum Pre-dose Serum Concentration (Ctrough,Max) Over the Multiple Dosing Phase for Cohort 4 | 440 mg Dose | 624 μg/mL | — |
Primary
Number of Subjects With TEAEs, Including by Severity, During Multiple-dose Phase
TEAEs were defined as AEs that developed or worsened after first dose of study drug (Day 1), and up to 30 days after last dose of study drug. The Investigator assessed AEs for severity and relatedness to study drug. AEs were graded according to CTCAE, v4.03 based on: Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe; Grade 4: Life-threatening; Grade 5: Death related to AE.
Time frame: From first dose of study drug up to 30 days after last dose of study drug (Cohorts 1-3: up to 58 days; Cohort 4: up to 759 days).
Population: The safety population included all enrolled subjects who received at least 1 dose of study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 1 Single-dose Phase | Number of Subjects With TEAEs, Including by Severity, During Multiple-dose Phase | Serious TEAE | 0 Participants |
| Cohort 1 Single-dose Phase | Number of Subjects With TEAEs, Including by Severity, During Multiple-dose Phase | Maximum severity of all TEAEs: life-threatening | 0 Participants |
| Cohort 1 Single-dose Phase | Number of Subjects With TEAEs, Including by Severity, During Multiple-dose Phase | TEAE leading to death | 0 Participants |
| Cohort 1 Single-dose Phase | Number of Subjects With TEAEs, Including by Severity, During Multiple-dose Phase | TEAE leading to study drug discontinuation | 1 Participants |
| Cohort 1 Single-dose Phase | Number of Subjects With TEAEs, Including by Severity, During Multiple-dose Phase | Maximum severity of all TEAEs: severe | 1 Participants |
| Cohort 1 Single-dose Phase | Number of Subjects With TEAEs, Including by Severity, During Multiple-dose Phase | TEAE at least possibly related to study drug | 0 Participants |
| Cohort 1 Single-dose Phase | Number of Subjects With TEAEs, Including by Severity, During Multiple-dose Phase | Any TEAE | 1 Participants |
| Cohort 1 Single-dose Phase | Number of Subjects With TEAEs, Including by Severity, During Multiple-dose Phase | Maximum severity of all TEAEs: moderate | 0 Participants |
| Cohort 1 Single-dose Phase | Number of Subjects With TEAEs, Including by Severity, During Multiple-dose Phase | Maximum severity of all TEAEs: mild | 0 Participants |
| Cohort 2 Single-dose Phase | Number of Subjects With TEAEs, Including by Severity, During Multiple-dose Phase | Maximum severity of all TEAEs: life-threatening | 0 Participants |
| Cohort 2 Single-dose Phase | Number of Subjects With TEAEs, Including by Severity, During Multiple-dose Phase | Any TEAE | 2 Participants |
| Cohort 2 Single-dose Phase | Number of Subjects With TEAEs, Including by Severity, During Multiple-dose Phase | TEAE at least possibly related to study drug | 1 Participants |
| Cohort 2 Single-dose Phase | Number of Subjects With TEAEs, Including by Severity, During Multiple-dose Phase | Serious TEAE | 0 Participants |
| Cohort 2 Single-dose Phase | Number of Subjects With TEAEs, Including by Severity, During Multiple-dose Phase | TEAE leading to study drug discontinuation | 0 Participants |
| Cohort 2 Single-dose Phase | Number of Subjects With TEAEs, Including by Severity, During Multiple-dose Phase | TEAE leading to death | 0 Participants |
| Cohort 2 Single-dose Phase | Number of Subjects With TEAEs, Including by Severity, During Multiple-dose Phase | Maximum severity of all TEAEs: mild | 0 Participants |
| Cohort 2 Single-dose Phase | Number of Subjects With TEAEs, Including by Severity, During Multiple-dose Phase | Maximum severity of all TEAEs: moderate | 2 Participants |
| Cohort 2 Single-dose Phase | Number of Subjects With TEAEs, Including by Severity, During Multiple-dose Phase | Maximum severity of all TEAEs: severe | 0 Participants |
| Cohort 3 Multiple-dose Phase | Number of Subjects With TEAEs, Including by Severity, During Multiple-dose Phase | Serious TEAE | 0 Participants |
| Cohort 3 Multiple-dose Phase | Number of Subjects With TEAEs, Including by Severity, During Multiple-dose Phase | TEAE leading to death | 0 Participants |
| Cohort 3 Multiple-dose Phase | Number of Subjects With TEAEs, Including by Severity, During Multiple-dose Phase | Any TEAE | 1 Participants |
| Cohort 3 Multiple-dose Phase | Number of Subjects With TEAEs, Including by Severity, During Multiple-dose Phase | Maximum severity of all TEAEs: mild | 1 Participants |
| Cohort 3 Multiple-dose Phase | Number of Subjects With TEAEs, Including by Severity, During Multiple-dose Phase | TEAE at least possibly related to study drug | 1 Participants |
| Cohort 3 Multiple-dose Phase | Number of Subjects With TEAEs, Including by Severity, During Multiple-dose Phase | Maximum severity of all TEAEs: life-threatening | 0 Participants |
| Cohort 3 Multiple-dose Phase | Number of Subjects With TEAEs, Including by Severity, During Multiple-dose Phase | Maximum severity of all TEAEs: moderate | 0 Participants |
| Cohort 3 Multiple-dose Phase | Number of Subjects With TEAEs, Including by Severity, During Multiple-dose Phase | Maximum severity of all TEAEs: severe | 0 Participants |
| Cohort 3 Multiple-dose Phase | Number of Subjects With TEAEs, Including by Severity, During Multiple-dose Phase | TEAE leading to study drug discontinuation | 0 Participants |
| Cohort 4 Multiple-dose Phase | Number of Subjects With TEAEs, Including by Severity, During Multiple-dose Phase | Maximum severity of all TEAEs: severe | 4 Participants |
| Cohort 4 Multiple-dose Phase | Number of Subjects With TEAEs, Including by Severity, During Multiple-dose Phase | Maximum severity of all TEAEs: moderate | 2 Participants |
| Cohort 4 Multiple-dose Phase | Number of Subjects With TEAEs, Including by Severity, During Multiple-dose Phase | TEAE leading to death | 0 Participants |
| Cohort 4 Multiple-dose Phase | Number of Subjects With TEAEs, Including by Severity, During Multiple-dose Phase | TEAE at least possibly related to study drug | 4 Participants |
| Cohort 4 Multiple-dose Phase | Number of Subjects With TEAEs, Including by Severity, During Multiple-dose Phase | Any TEAE | 6 Participants |
| Cohort 4 Multiple-dose Phase | Number of Subjects With TEAEs, Including by Severity, During Multiple-dose Phase | Maximum severity of all TEAEs: life-threatening | 0 Participants |
| Cohort 4 Multiple-dose Phase | Number of Subjects With TEAEs, Including by Severity, During Multiple-dose Phase | Maximum severity of all TEAEs: mild | 0 Participants |
| Cohort 4 Multiple-dose Phase | Number of Subjects With TEAEs, Including by Severity, During Multiple-dose Phase | Serious TEAE | 2 Participants |
| Cohort 4 Multiple-dose Phase | Number of Subjects With TEAEs, Including by Severity, During Multiple-dose Phase | TEAE leading to study drug discontinuation | 0 Participants |
Primary
Number of Subjects With Treatment-Emergent Adverse Events (TEAEs), Including by Severity, During Single-dose Phase
TEAEs were defined as AEs that developed or worsened after first dose of study drug (Day 1), and up to 30 days after last dose of study drug. The Investigator assessed AEs for severity and relatedness to study drug. AEs were graded according to the Common Terminology Criteria for Adverse Events (CTCAE, v4.03) based on: Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe; Grade 4: Life-threatening; Grade 5: Death related to AE.
Time frame: From single dose of study drug (Day 1) up to 30 days
Population: The safety population included all enrolled subjects who received at least 1 dose of study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 1 Single-dose Phase | Number of Subjects With Treatment-Emergent Adverse Events (TEAEs), Including by Severity, During Single-dose Phase | Any TEAE | 1 Participants |
| Cohort 1 Single-dose Phase | Number of Subjects With Treatment-Emergent Adverse Events (TEAEs), Including by Severity, During Single-dose Phase | TEAE at least possibly related to study drug | 0 Participants |
| Cohort 1 Single-dose Phase | Number of Subjects With Treatment-Emergent Adverse Events (TEAEs), Including by Severity, During Single-dose Phase | Serious TEAE | 0 Participants |
| Cohort 1 Single-dose Phase | Number of Subjects With Treatment-Emergent Adverse Events (TEAEs), Including by Severity, During Single-dose Phase | TEAE leading to study drug discontinuation | 0 Participants |
| Cohort 1 Single-dose Phase | Number of Subjects With Treatment-Emergent Adverse Events (TEAEs), Including by Severity, During Single-dose Phase | TEAE leading to death | 0 Participants |
| Cohort 1 Single-dose Phase | Number of Subjects With Treatment-Emergent Adverse Events (TEAEs), Including by Severity, During Single-dose Phase | Maximum severity of all TEAEs: mild | 0 Participants |
| Cohort 1 Single-dose Phase | Number of Subjects With Treatment-Emergent Adverse Events (TEAEs), Including by Severity, During Single-dose Phase | Maximum severity of all TEAEs: moderate | 1 Participants |
| Cohort 1 Single-dose Phase | Number of Subjects With Treatment-Emergent Adverse Events (TEAEs), Including by Severity, During Single-dose Phase | Maximum severity of all TEAEs: severe | 0 Participants |
| Cohort 2 Single-dose Phase | Number of Subjects With Treatment-Emergent Adverse Events (TEAEs), Including by Severity, During Single-dose Phase | Maximum severity of all TEAEs: severe | 0 Participants |
| Cohort 2 Single-dose Phase | Number of Subjects With Treatment-Emergent Adverse Events (TEAEs), Including by Severity, During Single-dose Phase | Any TEAE | 2 Participants |
| Cohort 2 Single-dose Phase | Number of Subjects With Treatment-Emergent Adverse Events (TEAEs), Including by Severity, During Single-dose Phase | TEAE leading to death | 0 Participants |
| Cohort 2 Single-dose Phase | Number of Subjects With Treatment-Emergent Adverse Events (TEAEs), Including by Severity, During Single-dose Phase | TEAE at least possibly related to study drug | 1 Participants |
| Cohort 2 Single-dose Phase | Number of Subjects With Treatment-Emergent Adverse Events (TEAEs), Including by Severity, During Single-dose Phase | Maximum severity of all TEAEs: moderate | 1 Participants |
| Cohort 2 Single-dose Phase | Number of Subjects With Treatment-Emergent Adverse Events (TEAEs), Including by Severity, During Single-dose Phase | Serious TEAE | 0 Participants |
| Cohort 2 Single-dose Phase | Number of Subjects With Treatment-Emergent Adverse Events (TEAEs), Including by Severity, During Single-dose Phase | Maximum severity of all TEAEs: mild | 1 Participants |
| Cohort 2 Single-dose Phase | Number of Subjects With Treatment-Emergent Adverse Events (TEAEs), Including by Severity, During Single-dose Phase | TEAE leading to study drug discontinuation | 0 Participants |