Pharmacology
Conditions
Brief summary
A First-in-Human, Double-blind, Randomized, Placebo-controlled, Single Ascending Dose Study to Assess Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of HM15912 in Healthy Korean Subjects
Interventions
DRUGHM15912
The study will be conducted in approximately 5 sequential dosing cohorts, enrolling 8 subjects per cohort. Subjects will be randomized to HM15912 or placebo in a ratio of 6:2 (6 active, 2 placebo).
DRUGPlacebo
The study will be conducted in approximately 5 sequential dosing cohorts, enrolling 8 subjects per cohort. Subjects will be randomized to HM15912 or placebo in a ratio of 6:2 (6 active, 2 placebo).
Sponsors
Hanmi Pharmaceutical Company Limited
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
19 Years to 60 Years
Healthy volunteers
Yes
Inclusion criteria
* Subject voluntarily agrees to participate in this study and signs an IRB-approved informed consent prior to performing any of the Screening visit procedures. * Korean males and females ≥ 19 and ≤ 60 years of age at the Screening visit
Exclusion criteria
* Subject with a history or presence of clinically significant active diseases. * Subject who has participated in other clinical studies (including bioequivalence tests) within 6 months before the Screening visit and has received IPs
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment-emergent Adverse Events of HM15912 | after single subcutaneous (SC) doses for 44 days | Number of participants with any treatment-emergent adverse events related to study medication. |
| Number of Participants With Significant Findings Observed for Hematology | after single subcutaneous (SC) doses for 44 days | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Concentration Max Profile of HM15912 | after single subcutaneous (SC) doses at day 1,2,3,4,5,6,7,10,17 and 30 | To assess the Concentration Max profile of HM15912 after single SC doses. |
Countries
South Korea
Participant flow
Recruitment details
Date of first enrollment was October 8th, 2019.
Pre-assignment details
The planned maximum dose of HM15912 was 1.5 mg/kg; however, higher doses were allowed to be administered if safety was confirmed in previous cohorts. If dose was escalated to more than 1.5 mg/kg, Ministry of Food and Drug Safety (MFDS) approval was to be obtained.
Participants by arm
| Arm | Count |
|---|---|
| HM15912 0.05mg/kg HM15912: The study will be conducted in approximately 5 sequential dosing cohorts, enrolling 8 subjects per cohort. Subjects will be randomized to HM15912 or placebo in a ratio of 6:2 (6 active, 2 placebo). | 6 |
| HM15912 0.1mg/kg HM15912: The study will be conducted in approximately 5 sequential dosing cohorts, enrolling 8 subjects per cohort. Subjects will be randomized to HM15912 or placebo in a ratio of 6:2 (6 active, 2 placebo). | 6 |
| HM15912 0.5mg/kg HM15912: The study will be conducted in approximately 5 sequential dosing cohorts, enrolling 8 subjects per cohort. Subjects will be randomized to HM15912 or placebo in a ratio of 6:2 (6 active, 2 placebo). | 6 |
| HM15912 1.0 mg/kg HM15912: The study will be conducted in approximately 5 sequential dosing cohorts, enrolling 8 subjects per cohort. Subjects will be randomized to HM15912 or placebo in a ratio of 6:2 (6 active, 2 placebo). | 6 |
| HM15912 1.5mg/kg HM15912: The study will be conducted in approximately 5 sequential dosing cohorts, enrolling 8 subjects per cohort. Subjects will be randomized to HM15912 or placebo in a ratio of 6:2 (6 active, 2 placebo). | 6 |
| Placebo Placebo: The study will be conducted in approximately 5 sequential dosing cohorts, enrolling 8 subjects per cohort. Subjects will be randomized to HM15912 or placebo in a ratio of 6:2 (6 active, 2 placebo). | 10 |
| Total | 40 |
Baseline characteristics
| Characteristic | HM15912 0.05mg/kg | HM15912 0.1mg/kg | HM15912 0.5mg/kg | HM15912 1.0 mg/kg | HM15912 1.5mg/kg | Placebo | Total |
|---|---|---|---|---|---|---|---|
| Age, Continuous | 31 Years STANDARD_DEVIATION 5.18 | 28.3 Years STANDARD_DEVIATION 8.87 | 26.0 Years STANDARD_DEVIATION 5.83 | 25.0 Years STANDARD_DEVIATION 3.52 | 31.7 Years STANDARD_DEVIATION 7.39 | 27.2 Years STANDARD_DEVIATION 2.39 | 28.4 Years STANDARD_DEVIATION 6.54 |
| Race/Ethnicity, Customized Korean | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 10 Participants | 40 Participants |
| Region of Enrollment South Korea | 6 participants | 6 participants | 6 participants | 6 participants | 6 participants | 10 participants | 40 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 10 Participants | 40 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 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 10 |
| other Total, other adverse events | 3 / 6 | 3 / 6 | 2 / 6 | 4 / 6 | 4 / 6 | 6 / 10 |
| serious Total, serious adverse events | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 10 |
Outcome results
Primary
Number of Participants With Significant Findings Observed for Hematology
Time frame: after single subcutaneous (SC) doses for 44 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| HM15912 0.05mg/kg | Number of Participants With Significant Findings Observed for Hematology | 0 Participants |
| HM15912 0.1mg/kg | Number of Participants With Significant Findings Observed for Hematology | 0 Participants |
| HM15912 0.5mg/kg | Number of Participants With Significant Findings Observed for Hematology | 0 Participants |
| HM15912 1.0mg/kg | Number of Participants With Significant Findings Observed for Hematology | 0 Participants |
| HM15912 1.5mg/kg | Number of Participants With Significant Findings Observed for Hematology | 0 Participants |
| Placebo | Number of Participants With Significant Findings Observed for Hematology | 0 Participants |
Primary
Number of Participants With Treatment-emergent Adverse Events of HM15912
Number of participants with any treatment-emergent adverse events related to study medication.
Time frame: after single subcutaneous (SC) doses for 44 days
Population: Each analysis population was included in the analyses, based on the actually administered IMP and dosage.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| HM15912 0.05mg/kg | Number of Participants With Treatment-emergent Adverse Events of HM15912 | Moderate TEAE | 0 Participants |
| HM15912 0.05mg/kg | Number of Participants With Treatment-emergent Adverse Events of HM15912 | Mild TEAE | 3 Participants |
| HM15912 0.05mg/kg | Number of Participants With Treatment-emergent Adverse Events of HM15912 | No AE | 3 Participants |
| HM15912 0.1mg/kg | Number of Participants With Treatment-emergent Adverse Events of HM15912 | Moderate TEAE | 2 Participants |
| HM15912 0.1mg/kg | Number of Participants With Treatment-emergent Adverse Events of HM15912 | Mild TEAE | 1 Participants |
| HM15912 0.1mg/kg | Number of Participants With Treatment-emergent Adverse Events of HM15912 | No AE | 3 Participants |
| HM15912 0.5mg/kg | Number of Participants With Treatment-emergent Adverse Events of HM15912 | Moderate TEAE | 0 Participants |
| HM15912 0.5mg/kg | Number of Participants With Treatment-emergent Adverse Events of HM15912 | Mild TEAE | 2 Participants |
| HM15912 0.5mg/kg | Number of Participants With Treatment-emergent Adverse Events of HM15912 | No AE | 4 Participants |
| HM15912 1.0mg/kg | Number of Participants With Treatment-emergent Adverse Events of HM15912 | Moderate TEAE | 0 Participants |
| HM15912 1.0mg/kg | Number of Participants With Treatment-emergent Adverse Events of HM15912 | Mild TEAE | 4 Participants |
| HM15912 1.0mg/kg | Number of Participants With Treatment-emergent Adverse Events of HM15912 | No AE | 2 Participants |
| HM15912 1.5mg/kg | Number of Participants With Treatment-emergent Adverse Events of HM15912 | Moderate TEAE | 0 Participants |
| HM15912 1.5mg/kg | Number of Participants With Treatment-emergent Adverse Events of HM15912 | Mild TEAE | 4 Participants |
| HM15912 1.5mg/kg | Number of Participants With Treatment-emergent Adverse Events of HM15912 | No AE | 2 Participants |
| Placebo | Number of Participants With Treatment-emergent Adverse Events of HM15912 | Mild TEAE | 5 Participants |
| Placebo | Number of Participants With Treatment-emergent Adverse Events of HM15912 | No AE | 4 Participants |
| Placebo | Number of Participants With Treatment-emergent Adverse Events of HM15912 | Moderate TEAE | 1 Participants |
Secondary
Concentration Max Profile of HM15912
To assess the Concentration Max profile of HM15912 after single SC doses.
Time frame: after single subcutaneous (SC) doses at day 1,2,3,4,5,6,7,10,17 and 30
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| HM15912 0.05mg/kg | Concentration Max Profile of HM15912 | 249.45 ng/mL | Geometric Coefficient of Variation 51.77 |
| HM15912 0.1mg/kg | Concentration Max Profile of HM15912 | 622.46 ng/mL | Geometric Coefficient of Variation 14.06 |
| HM15912 0.5mg/kg | Concentration Max Profile of HM15912 | 3550.79 ng/mL | Geometric Coefficient of Variation 36.44 |
| HM15912 1.0mg/kg | Concentration Max Profile of HM15912 | 8347.70 ng/mL | Geometric Coefficient of Variation 10.3 |
| HM15912 1.5mg/kg | Concentration Max Profile of HM15912 | 9393.06 ng/mL | Geometric Coefficient of Variation 13.24 |
| Placebo | Concentration Max Profile of HM15912 | 0 ng/mL | Geometric Coefficient of Variation 0 |