Study of CVN424 in Healthy Subjects
Study Details
Study Description
Brief Summary
This is a phase 1, randomized, double-blind, placebo-controlled, single- and multiple-dose ascending study in healthy subjects.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
Detailed Description
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Active Comparator: Single Ascending Dose The planned dose levels will be 1, 5, 25, 75, and 225 mg CVN424 and matching placebo. |
Drug: CVN424
SAD / MAD
Drug: Placebo
Placebo
|
| Active Comparator: Multiple Ascending Dose The planned dose levels will be 25, 75, and 150 mg CVN424 and matching placebo. |
Drug: CVN424
SAD / MAD
Drug: Placebo
Placebo
|
Outcome Measures
Primary Outcome Measures
- Evaluation of adverse events [Baseline through 14 days post-dose]
Occurrence of all adverse events from signing of informed consent through end of study treatment.
- Evaluation of Hematology [Baseline through 14 days post-dose]
RBC
- Evaluation of Vital Signs [Baseline through 14 days post-dose]
Oral Temperature (°C )
- Evaluation of Electrocardiograms [Baseline through 14 days post-dose]
Standard 12-lead ECG - QT interval
- Evaluation of BMI [Baseline through 14 days post-dose]
Weight and Height will be combined to calculate BMI using the following formula: BMI = weight (kg)/[height (m)]2
- Evaluation of Serum Chemistry [Baseline through 14 days post-dose]
ALT
- Evaluation of Urinalysis [Baseline through 14 days post-dose]
pH
- Evaluation of Vital Signs [Baseline through 14 days post-dose]
Respiration rate
- Evaluation of Vital Signs [Baseline through 14 days post-dose]
Pulse rate
- Evaluation of Vital Signs [Baseline through 14 days post-dose]
Blood pressure (both systolic and diastolic)
- Evaluation of Hematology [Baseline through 14 days post-dose]
WBC with differential (%and absolute) platelets, PT/INR
- Evaluation of Hematology [Baseline through 14 days post-dose]
Hemoglobin
- Evaluation of Hematology [Baseline through 14 days post-dose]
Hematocrit
- Evaluation of Hematology [Baseline through 14 days post-dose]
PT/INR
- Evaluation of Hematology [Baseline through 14 days post-dose]
Platelets
- Evaluation of Electrocardiograms [Baseline through 14 days post-dose]
Standard 12-lead ECG- QTcB interval
- Evaluation of Electrocardiograms [Baseline through 14 days post-dose]
Standard 12-lead ECG - QTcF interval
- Evaluation of Electrocardiograms [Baseline through 14 days post-dose]
Standard 12-lead ECG - RR interval
- Evaluation of Electrocardiograms [Baseline through 14 days post-dose]
Standard 12-lead ECG - QRS interval
- Evaluation of Electrocardiograms [Baseline through 14 days post-dose]
Standard 12-lead ECG - PR interval
- Evaluation of Serum Chemistry [Baseline through 14 days post-dose]
Albumin
- Evaluation of Serum Chemistry [Baseline through 14 days post-dose]
Alkaline phosphatase
- Evaluation of Serum Chemistry [Baseline through 14 days post-dose]
Lipase
- Evaluation of Serum Chemistry [Baseline through 14 days post-dose]
AST
- Evaluation of Serum Chemistry [Baseline through 14 days post-dose]
Total bilirubin
- Evaluation of Serum Chemistry [Baseline through 14 days post-dose]
Direct bilirubin
- Evaluation of Serum Chemistry [Baseline through 14 days post-dose]
Total protein
- Evaluation of Serum Chemistry [Baseline through 14 days post-dose]
Creatinine
- Evaluation of Serum Chemistry [Baseline through 14 days post-dose]
Blood urea nitrogen
- Evaluation of Serum Chemistry [Baseline through 14 days post-dose]
Creatine kinase Glucose, Chloride, Bicarbonate
- Evaluation of Serum Chemistry [Baseline through 14 days post-dose]
GGT
- Evaluation of Serum Chemistry [Baseline through 14 days post-dose]
Potassium
- Evaluation of Serum Chemistry [Baseline through 14 days post-dose]
Sodium
- Evaluation of Serum Chemistry [Baseline through 14 days post-dose]
Glucose
- Evaluation of Serum Chemistry [Baseline through 14 days post-dose]
Chloride
- Evaluation of Serum Chemistry [Baseline through 14 days post-dose]
Bicarbonate
- Evaluation of Serum Chemistry [Baseline through 14 days post-dose]
Calcium
- Evaluation of Urinalysis [Baseline through 14 days post-dose]
Specific gravity
- Evaluation of Urinalysis [Baseline through 14 days post-dose]
Protein
- Evaluation of Urinalysis [Baseline through 14 days post-dose]
Glucose
- Evaluation of Urinalysis [Baseline through 14 days post-dose]
Blood
- Evaluation of Urinalysis [Baseline through 14 days post-dose]
Nitrite
- Evaluation of Urinalysis [Baseline through 14 days post-dose]
Microscopic Analysis (only if positive dipstick results): RBC/high power field, WBC/high power field, Epithelial cells, casts
Secondary Outcome Measures
- Plasma Concentration (AUC) of CVN424 [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)]
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)
- Plasma Concentration (Cmax) of CVN424 [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)]
To evaluate the pharmacokinetics of single and multiple doses of CVN424. Pharmacokinetic parameters including, but not limited to maximum plasma concentration (Cmax).
- Food effect by measurement of plasma PK (Cmax) [Baseline through 14 days post-dose]
Assess the effect of food on the bioavailability in the current formulation after digesting a high caloric meal.
- Food effect by measurement of plasma PK (AUC) [Baseline through 14 days post-dose]
Assess the effect of food on the bioavailability in the current formulation after digesting a high caloric meal.
Other Outcome Measures
- DNA isolation and genotyping [Day 1]
Drug metabolic enzyme and transporter polymorphisms that may contribute to variability in CVN424 will be reported. Single-dose -pre-dose Multi-dose -pre-dose
- RNA isolation and genotyping [Day 1 and Day 7]
Single-dose -pre-dose, 8 and 24 hours post dose Multi-dose -pre-dose, 8 and 24 hours post dose
Eligibility Criteria
Criteria
Inclusion Criteria:
-
In the opinion of the Investigator, the subject is capable of understanding and complying with protocol requirements.
-
The subject signs and dates a written informed consent form (ICF) and any required privacy authorization prior to the initiation of any study procedures.
-
Subject is a healthy male or female adult who is 18 to 50 years of age inclusive at the time of ICF and study drug dosing.
-
Subject weighs at least 45 kg (99 lbs) and has a BMI between 18.0 and 30.0 kg/m2, inclusive at Screening.
-
A male subject who is nonsterilized and sexually active with a female partner of childbearing potential* agrees to use adequate contraception* from signing of the ICF throughout the duration of the study and for 12 weeks after last dose.
-
A female subject with no childbearing potential, defined as the subject has been surgically sterilized (hysterectomy, bilateral oophorectomy or tubal ligation) or who are postmenopausal (defined as continuous amenorrhea of at least 2 years and FSH>40 IU/L).
Exclusion Criteria:
-
Subjects have a known hypersensitivity to any component of the formulation of CVN424.
-
Subjects have evidence of CS neurologic, cardiovascular, pulmonary, hepatic, hematopoietic disease, renal, metabolic, gastrointestinal, urologic, immunologic, endocrine disease, serious allergy, allergic skin rash, psychiatric disorder, or other abnormality that may impact the ability of the subject to participate or potentially confound the study results.
-
There is any finding in the subject's medical history, physical examination, or safety laboratory tests giving reasonable suspicion of a condition that might interfere with the conduct or interpretation of the study.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | PPD Development, LP | Austin | Texas | United States | 78744 |
Sponsors and Collaborators
- Cerevance Beta, Inc.
Investigators
- Study Director: David H Margolin, MD, PhD, Cerevance, Inc.
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- CVN424-101