Study of CVN424 in Healthy Subjects (CVN424)

A Phase 1, Randomized, Double-Blind, Placebo-Controlled, Safety, Tolerability, and Pharmacokinetic Study of Escalating Single and Multiple Doses of CVN424 in Healthy Subjects

This is a phase 1, randomized, double-blind, placebo-controlled, single- and multiple-dose ascending study in healthy subjects.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Placebo; Drug: CVN424

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 Type: Interventional
• Enrollment (Actual): 64
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Texas
    • Austin, Texas, United States, 78744
      • PPD Development, LP

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / 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: Placebo; Placebo; Drug: CVN424; SAD / MAD
Active Comparator: Multiple Ascending Dose; The planned dose levels will be 25, 75, and 150 mg CVN424 and matching placebo.	Drug: Placebo; Placebo; Drug: CVN424; SAD / MAD

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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
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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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)
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)

Other Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Cerevance Beta, Inc.
• Investigators: Study Director: David H Margolin, MD, PhD, Cerevance, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): September 18, 2018
• Primary Completion (Actual): March 1, 2019
• Study Completion (Actual): May 30, 2019

Study Registration Dates

• First Submitted: August 24, 2018
• First Submitted That Met QC Criteria: August 31, 2018
• First Posted (Actual): September 4, 2018

Study Record Updates

• Last Update Posted (Actual): July 23, 2019
• Last Update Submitted That Met QC Criteria: July 22, 2019
• Last Verified: July 1, 2019

More Information

Terms related to this study

• Keywords: Healthy Volunteers
• Other Study ID Numbers: CVN424-101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No