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This study is being done to test a new injection called MWX205 in people with high cholesterol or fat levels in the blood (dyslipidemia).
Researchers will check if a single dose of MWX205 is safe and how the body reacts to it. They will also measure how quickly the drug enters the bloodstream and how long it stays in the body, and compare it with a placebo (inactive treatment).
The study will help decide the right dose and understand how this medicine could be used in future treatments.
The main questions this study aims to answer are:
This is a Phase 1, randomized, double-blind, placebo-controlled, single ascending dose study in which the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and immunogenicity of MWX205 Injection will be assessed in adult participants with dyslipidemia.
Overall, 37 participants will be enrolled and assigned to 5 sequential cohorts (Cohorts 1 through 5).
Cohort 1 will enroll 5 participants and be randomized 3:2 to receive a single dose of MWX205 or placebo (3 participants receiving MWX205 and 2 receiving a placebo).
Cohorts 2 to 5 will be comprised of 8 participants per Cohort and randomized 3:1 to receive a single dose of MWX205 or placebo, respectively (6 participants receiving MWX205 Injection and 2 receiving a placebo).
Dosing in each cohort will be such that 2 participants (1 MWX205 Injection and 1 placebo) will be administered at least 24 hours before the remaining 3 participants (the first cohort) or 6 participants (cohorts 2-5). After dosing the first 2 participants on a separate day, a minimum of a 5-minute dosing interval for the remaining 3 participants (the first cohort), or 6 participants (cohorts 2-5) in the following cohort, is considered acceptable.
Continuation to dose the remaining 3 participants (Cohort 1) or 6 participants (Cohorts 2-5) will be at the investigator's discretion.
Each participant will participate in 1 cohort only, residing at the Clinical Research Unit (CRU) from Day -1 (the day before dosing) to Day 8.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| MWX205 | Experimental | Strength: 1ml: 200 mg Proposed dose levels for SAD study: 50, 200, 400, 800, and 1200 mg Administration: subcutaneous injection, recommended in the abdomen. |
|
| Placebo | Placebo Comparator | Administration: subcutaneous injection, recommended in the abdomen. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| MWX205 | Drug | Each vial contains 200mg of MWX205 small nucleic acid, with water for injection as the solvent. The excipient, including sodium hydroxide and/or hydrochloric acid, may be added to adjust the pH to 6.5±0.2. |
| Measure | Description | Time Frame |
|---|---|---|
| Incidence of TEAEs | From Day 1 to Day 86 | |
| Incidence of SAEs | From Day 1 to Day 86 | |
| Number of participants with abnormal vital signs | Vital signs include tympanic body temperature, systolic and diastolic blood pressure, pulse rate, and respiratory rate | From Day 1 to Day 86 |
| Number of participants with abnormal Physical examination findings | Complete physical examinations include general appearance, mouth/dental (if required), neck (including thyroid & nodes), cardiovascular, respiratory, gastrointestinal, renal, neurological, musculoskeletal, skin, other | From Day 1 to Day 337 |
| Number of participants with abnormal ECG readings | 12 Lead ECG: Triplicate readings to be taken within 2 to 5 minutes of each other. ECGs are to be taken after the participant has rested in the supine position for ≥ 5 minutes | From Day 1 to Day 337 |
| Measure | Description | Time Frame |
|---|---|---|
| Plasma PK parameters Cmax (Maximum observed plasma drug concentration directly determined from the plasma concentration-time profiles) | Non-compartmental analysis (NCA) will be used to calculate the PK parameters with Phoenix WinNonlin Software | Day 1, Day 2, Day 3 |
| Plasma PK parameters- Tmax (Time to maximum observed plasma drug concentration) |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Mohd Naguib bin Mohd Yunos, Dr. | Contact | +61 0387361750 | naguibyunos@veritusresearch.com |
| Name | Affiliation | Role |
|---|---|---|
| Mohd Naguib bin Mohd Yunos, Dr. | Veritus Research | Principal Investigator |
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| ID | Term |
|---|---|
| D050171 | Dyslipidemias |
| ID | Term |
|---|---|
| D052439 | Lipid Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
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| Placebo | Drug | Matching placebo |
|
Non-compartmental analysis (NCA) will be used to calculate the PK parameters with Phoenix WinNonlin Software |
| Day 1, Day 2, Day 3 |
| Plasma PK parameters- AUC0-inf (Area under the plasma concentration-time curve from time 0 extrapolated to infinity.) | Non-compartmental analysis (NCA) will be used to calculate the PK parameters with Phoenix WinNonlin Software | Day 1, Day 2, Day 3 |
| Plasma PK parameters- AUC0-last (Area under the plasma concentration-time curve, from time zero to the last time point with measurable analyte concentration) | Non-compartmental analysis (NCA) will be used to calculate the PK parameters with Phoenix WinNonlin Software | Day 1, Day 2, Day 3 |
| Urine PK parameters- Fe (dose fraction of the drug in its original form excreted in urine after administration) | Non-compartmental analysis (NCA) will be used to calculate the PK parameters with Phoenix WinNonlin Software | Day 1, Day 2, Day 3 |
| Urine PK parameters- Ae (cumulative excretion of the drug's original form in urine) | Non-compartmental analysis (NCA) will be used to calculate the PK parameters with Phoenix WinNonlin Software | Day 1, Day 2, Day 3 |