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This is a phase 1, randomized, double-blind, placebo-controlled, single- and multiple-dose ascending study in healthy subjects.
Part 1: Single-Dose Regimen and Fasted-Fed Crossover - For the single-dose regimen, approximately 40 healthy male and female subjects will be enrolled in 1 of 5 single dose cohorts (designated as S1 through S5, respectively) in an ascending fashion.
Part 2: Multiple-Dose Regimen
- For the multiple-dose regimen, approximately 24 healthy male and female subjects age 18 to 50 years old will be enrolled in 1 of the 3 multiple-dose cohorts (designated as M1 through M3, respectively) in an ascending fashion.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Single Ascending Dose | Active Comparator | The planned dose levels will be 1, 5, 25, 75, and 225 mg CVN424 and matching placebo. |
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| Multiple Ascending Dose | Active Comparator | The planned dose levels will be 25, 75, and 150 mg CVN424 and matching placebo. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| CVN424 | Drug | SAD / MAD |
| |
| Measure | Description | Time Frame |
|---|---|---|
| Evaluation of adverse events | Occurrence of all adverse events from signing of informed consent through end of study treatment. | Baseline through 14 days post-dose |
| Evaluation of Hematology | RBC | Baseline through 14 days post-dose |
| Evaluation of Vital Signs | Oral Temperature (°C ) | Baseline through 14 days post-dose |
| Evaluation of Electrocardiograms | Standard 12-lead ECG - QT interval | Baseline through 14 days post-dose |
| Evaluation of BMI | Weight and Height will be combined to calculate BMI using the following formula: BMI = weight (kg)/[height (m)]2 | Baseline through 14 days post-dose |
| Evaluation of Serum Chemistry | ALT | Baseline through 14 days post-dose |
| Evaluation of Urinalysis | pH | Baseline through 14 days post-dose |
| Evaluation of Vital Signs | Respiration rate | Baseline through 14 days post-dose |
| Measure | Description | Time Frame |
|---|---|---|
| Plasma Concentration (AUC) of CVN424 | To evaluate the pharmacokinetics of single and multiple doses of CVN424. Pharmacokinetic parameters including, but not limited to area under the plasma concentration-time curve (AUC) from 0 to 24hours (AUC0-24) | SAD: PK Collection on Day 1-4, and early termination (up to 8 days); MAD: PK Collection on Day 1-10, and early termination (up to 14 days) |
| Measure | Description | Time Frame |
|---|---|---|
| DNA isolation and genotyping | Drug metabolic enzyme and transporter polymorphisms that may contribute to variability in CVN424 will be reported. Single-dose -pre-dose Multi-dose -pre-dose | Day 1 |
| RNA isolation and genotyping |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| David H Margolin, MD, PhD | Cerevance, Inc. | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| PPD Development, LP | Austin | Texas | 78744 | United States |
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| Type | Date | Date Unknown |
|---|---|---|
| Release | Mar 11, 2024 | |
| Reset | Aug 14, 2024 | |
| Release | Aug 23, 2024 | |
| Reset | Sep 3, 2024 |
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| Release Date | Unrelease Date | Unrelease Date Unknown | Reset Date | MCP Release Number |
|---|---|---|---|---|
| Mar 11, 2024 | Aug 14, 2024 | |||
| Aug 23, 2024 |
Single ascending dose and multiple ascending dose study
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| Placebo |
| Drug |
Placebo |
|
| Evaluation of Vital Signs |
Pulse rate |
| Baseline through 14 days post-dose |
| Evaluation of Vital Signs | Blood pressure (both systolic and diastolic) | Baseline through 14 days post-dose |
| Evaluation of Hematology | WBC with differential (%and absolute) platelets, PT/INR | Baseline through 14 days post-dose |
| Evaluation of Hematology | Hemoglobin | Baseline through 14 days post-dose |
| Evaluation of Hematology | Hematocrit | Baseline through 14 days post-dose |
| Evaluation of Hematology | PT/INR | Baseline through 14 days post-dose |
| Evaluation of Hematology | Platelets | Baseline through 14 days post-dose |
| Evaluation of Electrocardiograms | Standard 12-lead ECG- QTcB interval | Baseline through 14 days post-dose |
| Evaluation of Electrocardiograms | Standard 12-lead ECG - QTcF interval | Baseline through 14 days post-dose |
| Evaluation of Electrocardiograms | Standard 12-lead ECG - RR interval | Baseline through 14 days post-dose |
| Evaluation of Electrocardiograms | Standard 12-lead ECG - QRS interval | Baseline through 14 days post-dose |
| Evaluation of Electrocardiograms | Standard 12-lead ECG - PR interval | Baseline through 14 days post-dose |
| Evaluation of Serum Chemistry | Albumin | Baseline through 14 days post-dose |
| Evaluation of Serum Chemistry | Alkaline phosphatase | Baseline through 14 days post-dose |
| Evaluation of Serum Chemistry | Lipase | Baseline through 14 days post-dose |
| Evaluation of Serum Chemistry | AST | Baseline through 14 days post-dose |
| Evaluation of Serum Chemistry | Total bilirubin | Baseline through 14 days post-dose |
| Evaluation of Serum Chemistry | Direct bilirubin | Baseline through 14 days post-dose |
| Evaluation of Serum Chemistry | Total protein | Baseline through 14 days post-dose |
| Evaluation of Serum Chemistry | Creatinine | Baseline through 14 days post-dose |
| Evaluation of Serum Chemistry | Blood urea nitrogen | Baseline through 14 days post-dose |
| Evaluation of Serum Chemistry | Creatine kinase Glucose, Chloride, Bicarbonate | Baseline through 14 days post-dose |
| Evaluation of Serum Chemistry | GGT | Baseline through 14 days post-dose |
| Evaluation of Serum Chemistry | Potassium | Baseline through 14 days post-dose |
| Evaluation of Serum Chemistry | Sodium | Baseline through 14 days post-dose |
| Evaluation of Serum Chemistry | Glucose | Baseline through 14 days post-dose |
| Evaluation of Serum Chemistry | Chloride | Baseline through 14 days post-dose |
| Evaluation of Serum Chemistry | Bicarbonate | Baseline through 14 days post-dose |
| Evaluation of Serum Chemistry | Calcium | Baseline through 14 days post-dose |
| Evaluation of Urinalysis | Specific gravity | Baseline through 14 days post-dose |
| Evaluation of Urinalysis | Protein | Baseline through 14 days post-dose |
| Evaluation of Urinalysis | Glucose | Baseline through 14 days post-dose |
| Evaluation of Urinalysis | Blood | Baseline through 14 days post-dose |
| Evaluation of Urinalysis | Nitrite | Baseline through 14 days post-dose |
| Evaluation of Urinalysis | Microscopic Analysis (only if positive dipstick results): RBC/high power field, WBC/high power field, Epithelial cells, casts | Baseline through 14 days post-dose |
| Plasma Concentration (Cmax) of CVN424 | To evaluate the pharmacokinetics of single and multiple doses of CVN424. Pharmacokinetic parameters including, but not limited to maximum plasma concentration (Cmax). | SAD: PK Collection on Day 1-4, and early termination (up to 8 days); MAD: PK Collection on Day 1-10, and early termination (up to 14 days) |
| Food effect by measurement of plasma PK (Cmax) | Assess the effect of food on the bioavailability in the current formulation after digesting a high caloric meal. | Baseline through 14 days post-dose |
| Food effect by measurement of plasma PK (AUC) | Assess the effect of food on the bioavailability in the current formulation after digesting a high caloric meal. | Baseline through 14 days post-dose |
Single-dose -pre-dose, 8 and 24 hours post dose
Multi-dose
-pre-dose, 8 and 24 hours post dose
| Day 1 and Day 7 |
| Sep 3, 2024 |