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Relative Bioavailability and Food Effect Study of CVN424

Primary Purpose

Parkinson Disease

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
CVN424
Sponsored by
Cerevance Beta, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Parkinson Disease

Eligibility Criteria

18 Years - 55 Years (Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria: In the Investigator's opinion, the participant can understand and sign the Informed Consent Form (ICF) and comply with all protocol requirements. 2. The participant is male or female adult who is 18 to 55 years of age, inclusive at the time of Screening. Participant weighs at least 45 kilograms (kg) (99 pounds [lbs]) and has a BMI between 18.0 and 35.0 kg/m2, inclusive at Screening. The participant is medically healthy with no clinically significant (CS) or relevant abnormalities in medical history, physical exam, vital signs, ECG, and laboratory evaluations (hematology, chemistry, and urinalysis) as assessed by the Investigator. Female participants of childbearing potential and male participants with female partners of childbearing potential must agree to either remain abstinent or use two methods of adequate and reliable contraception (see Section 9.1.12) throughout the study and at least 12 weeks after the last dose of study drug has been taken. Exclusion Criteria: Vegetarian, Vegan, Lactose intolerant, or follows a Kosher diet. Evidence of clinically significant neurologic or other disorder or impairment that, in the opinion of the Investigator, is reasonably expected to impact the ability of the participant to participate or confound the study results. A current or recent (within 6 months) gastrointestinal disease that would be expected to influence the absorption of drugs (i.e., a history of malabsorption, any surgical intervention known to impact absorption [e.g., bariatric surgery or bowel resection]). Note, history of cholecystectomy is permitted if there is no evidence of malabsorption per the Investigator. A history of cancer or other malignancy, with the exception of low-grade cervical intraepithelial neoplasia, low-grade (low-risk) prostate cancer, or 5-year cancer-free survivors of basal or squamous cell carcinoma or higher-grade cervical intraepithelial neoplasia or prostate cancer. A positive test result for hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibody, or a human immunodeficiency virus (HIV) infection at Screening. Any clinically significant abnormalities in labs: biochemistry (including liver function test [LFT], estimated glomerular filtration rate [eGFR], and glucose), standard DocuSign Envelope ID: EB6849FB-17AD-4CBA-BC47-4D1BE77C1D88 CVN424Study No. CVN424-102Page 24of 64Clinical Protocol Version 1.030Aug2022hematology with white blood cell (WBC) differential, c-reactive protein (CRP), coagulation tests, lipase, amylase, albumin, and calcium. A supine blood pressure outside the ranges of 80 to 160 mm Hg for systolic and 50 to 100 mm Hg for diastolic, confirmed with up to two repeat tests at the Screening Visit; or symptomatic orthostatic hypotension, in the opinion of the Investigator. A resting heart rate outside the range of 40 to 100 beats per minute (bpm) confirmed with up to two repeat tests at the Screening Visit. Note that 40-50 and 90-100 bpm may be permitted only at the discretion of the Investigator. Positive urine result for illegal drugs at Screening and Check-In, or history of illicit drug use or alcohol abuse within 1 year prior to the Screening Visit. Received any investigational compound (defined as a drug that has not been FDA-approved) within 30 days prior to the first dose of study medication or within 5 half-lives of the investigational compound, whichever is greater. Within 14 or 28 days prior to randomization, ingested any of the following excluded medication, supplements, or food products: St. John's wort, ginseng, kava, Ginkgo biloba, Chinese herbs, and melatonin, or known strong inhibitors/inducers of cytochrome P-4503A4/5, including rifampin, clarithromycin, ketoconazole, itraconazole. For full list of prohibited medications and dietary products, (See Table 2 in full protocol). Regularly uses nicotine-containing products (including but not limited to cigarettes, electronic cigarettes, pipes, cigars, chewing tobacco, nicotine patch, or nicotine gum). The casual users (≤ 10 cigarettes/week) may participate; however, they must agree to refrain from 30 days before Day 0 (Inpatient Check-in) for the duration of the study or a positive urine cotinine test at Inpatient Check-in. Known history of coronary artery disease and hospitalization for myocardial infraction, ischemic heart disease, or congestive heart failure within the 2 years prior to the screening visit. Any clinically significant medical, psychiatric, or laboratory abnormality that, in the judgment of the Investigator, is likely to interfere with study participation A history of major depression or risk of suicide according to the Investigator's clinical judgment or has made a suicide attempt. Is a study site employee or an immediate family member of a study site employee

Sites / Locations

  • Celerion

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Active Comparator

Active Comparator

Active Comparator

Arm Label

Suspension (fasted)

Tablet (fed)

Tablet (fasted)

Arm Description

150 milligrams (mg) of CVN424 administered in a single dose of suspension formulation.

150 milligrams (mg) tablet of CVN424 administered in a single dose after ingestion of a standardized high-fat, high-calorie meal according to FDA Guidance for Industry (Food-effect bioavailability and fed bioequivalence studies, Jun 2022).

150 milligrams (mg) tablet of CVN424 administered in a single dose.

Outcomes

Primary Outcome Measures

The relative bioavailability of the CVN424 solution and CVN424 tablet formulation in the fasted state.
Plasma PK parameters and maximum observed plasma concentration of CVN424 solution and CVN424 tablet formulation in the fasted state will be used to determine the relative bioavailability of CVN424 suspension to tablet.

Secondary Outcome Measures

The effects of food on the rate and extent of absorption of CVN424 150mg tablet when administered in fed conditions compared to administration under fasting conditions.
The ratio of the PK parameters between CVN424 tablets in the fed and fasted state will be calculated and summarized descriptively.
Number of participants who experience Treatment Emergent Adverse Events (TEAEs) related to CVN424 Tablet under fast and fed conditions
Assessment of safety as measured by TEAEs and tolerability as measured by discontinuations due to AE. AEs that occur from first dosing until 30 days after the last dose will be captured as a treatment-emergent AE (TEAE).

Full Information

First Posted
November 7, 2022
Last Updated
November 30, 2022
Sponsor
Cerevance Beta, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT05635461
Brief Title
Relative Bioavailability and Food Effect Study of CVN424
Official Title
A Randomized, Open-Label, Single Oral Dose, Three-Way Cross-Over Trial to Evaluate the Relative Bioavailability of CVN424 Suspension &Tablet Formulations Including an Assessment of the Effect of Food on the Tablet Formulation in Healthy Adult Volunteers
Study Type
Interventional

2. Study Status

Record Verification Date
November 2022
Overall Recruitment Status
Completed
Study Start Date
October 9, 2022 (Actual)
Primary Completion Date
November 11, 2022 (Actual)
Study Completion Date
November 21, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Cerevance Beta, Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
This is a Randomized, Open-Label, Single Oral Dose, Three-Way Cross-Over Trial to Evaluate the Relative Bioavailability of CVN424 Suspension and Tablet Formulations in Healthy Volunteers Under Fasted and Fed Conditions.
Detailed Description
32 healthy male or female participants will be enrolled in 1 of 6 sequences (designated as 1 through 6, respectively) in an ascending fashion. Sequences 1, 3, 4, and 5 will have 5 participants each, and Sequences 2 and 6 will have 6 participants each. Each sequence will proceed through the three cross-overs (suspension-fasted, tablet-fed, and tablet-fasted) according to the schematic above, with dosing to occur on Days 1 of Periods 1, 2, and 3. Participants in the fasted portion of each sequence will be dosed under overnight fasted conditions and will remain fasted for 4 hours post-dose. Water consumption is permitted as desired except for 1 hour before and after administration of the Study Drug. To assess the effect of food on CVN424 bioavailability in tablet formulation, the single dose will be administered after ingestion of a standardized high-fat, high-calorie meal according to FDA Guidance for Industry (Food-effect bioavailability and fed bioequivalence studies, Jun 2022). Participants for all sequences will be admitted to the study unit 1 day prior to dosing and remain in the unit for safety and pharmacokinetics (PK) assessments through 96 hours post-dose. The total confinement period will be 5 nights for each period unless extended at the discretion of the Investigator, e.g., for monitoring and/or management of adverse events (AEs). Once 96-hour post-dose PK has been collected, participants will be discharged from the unit for the remainder of the washout period and return the day prior to their next scheduled dosing period

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Parkinson Disease

7. Study Design

Primary Purpose
Basic Science
Study Phase
Phase 1
Interventional Study Model
Crossover Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
32 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Suspension (fasted)
Arm Type
Active Comparator
Arm Description
150 milligrams (mg) of CVN424 administered in a single dose of suspension formulation.
Arm Title
Tablet (fed)
Arm Type
Active Comparator
Arm Description
150 milligrams (mg) tablet of CVN424 administered in a single dose after ingestion of a standardized high-fat, high-calorie meal according to FDA Guidance for Industry (Food-effect bioavailability and fed bioequivalence studies, Jun 2022).
Arm Title
Tablet (fasted)
Arm Type
Active Comparator
Arm Description
150 milligrams (mg) tablet of CVN424 administered in a single dose.
Intervention Type
Drug
Intervention Name(s)
CVN424
Intervention Description
150 mg of either tablet or suspension formulation
Primary Outcome Measure Information:
Title
The relative bioavailability of the CVN424 solution and CVN424 tablet formulation in the fasted state.
Description
Plasma PK parameters and maximum observed plasma concentration of CVN424 solution and CVN424 tablet formulation in the fasted state will be used to determine the relative bioavailability of CVN424 suspension to tablet.
Time Frame
Time 0 (time of dosing) to 96 hours post-dose for each treatment condition.
Secondary Outcome Measure Information:
Title
The effects of food on the rate and extent of absorption of CVN424 150mg tablet when administered in fed conditions compared to administration under fasting conditions.
Description
The ratio of the PK parameters between CVN424 tablets in the fed and fasted state will be calculated and summarized descriptively.
Time Frame
Time 0 (time of dosing) to 96 hours post-dose for each treatment condition.
Title
Number of participants who experience Treatment Emergent Adverse Events (TEAEs) related to CVN424 Tablet under fast and fed conditions
Description
Assessment of safety as measured by TEAEs and tolerability as measured by discontinuations due to AE. AEs that occur from first dosing until 30 days after the last dose will be captured as a treatment-emergent AE (TEAE).
Time Frame
Baseline through 30 days after study drug administration
Other Pre-specified Outcome Measures:
Title
Characterization of metabolic enzyme and transporter polymorphisms
Description
Plasma samples will be archived for potential analysis of metabolites.
Time Frame
Baseline through 96 hours post dose of period 3 (overall study day 32)
Title
Characterization of metabolic enzyme and transporter polymorphisms
Description
Plasma samples will be archived for potential analysis of target-related biomarkers.
Time Frame
Baseline through 96 hours post dose of period 3 (overall study day 32)
Title
Characterization of metabolic enzyme and transporter polymorphisms
Description
Urine samples will be archived for potential analysis of metabolites.
Time Frame
Baseline through 96 hours post dose of period 3 (overall study day 32)
Title
Characterization of metabolic enzyme and transporter polymorphisms
Description
Urine samples will be archived for potential analysis of target-related biomarkers.
Time Frame
Baseline through 96 hours post dose of period 3 (overall study day 32)
Title
Calculation of urine PK parameters
Description
Assessment of urine concentrations.
Time Frame
Baseline through 96 hours post dose of period 3 (overall study day 32)
Title
Calculation of urine PK parameters
Description
Assessment of urine volumes.
Time Frame
Baseline through 96 hours post dose of period 3 (overall study day 32)
Title
Calculation of urine PK parameters
Description
Assessment of cumulative amount of unchanged drug excreted into the urine.
Time Frame
Baseline through 96 hours post dose of period 3 (overall study day 32)
Title
Calculation of urine PK parameters
Description
Assessment of fraction of unchanged drug excreted in the urine.
Time Frame
Baseline through 96 hours post dose of period 3 (overall study day 32)
Title
Calculation of urine PK parameters
Description
Assessment of renal clearance.
Time Frame
Baseline through 96 hours post dose of period 3 (overall study day 32)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: In the Investigator's opinion, the participant can understand and sign the Informed Consent Form (ICF) and comply with all protocol requirements. 2. The participant is male or female adult who is 18 to 55 years of age, inclusive at the time of Screening. Participant weighs at least 45 kilograms (kg) (99 pounds [lbs]) and has a BMI between 18.0 and 35.0 kg/m2, inclusive at Screening. The participant is medically healthy with no clinically significant (CS) or relevant abnormalities in medical history, physical exam, vital signs, ECG, and laboratory evaluations (hematology, chemistry, and urinalysis) as assessed by the Investigator. Female participants of childbearing potential and male participants with female partners of childbearing potential must agree to either remain abstinent or use two methods of adequate and reliable contraception (see Section 9.1.12) throughout the study and at least 12 weeks after the last dose of study drug has been taken. Exclusion Criteria: Vegetarian, Vegan, Lactose intolerant, or follows a Kosher diet. Evidence of clinically significant neurologic or other disorder or impairment that, in the opinion of the Investigator, is reasonably expected to impact the ability of the participant to participate or confound the study results. A current or recent (within 6 months) gastrointestinal disease that would be expected to influence the absorption of drugs (i.e., a history of malabsorption, any surgical intervention known to impact absorption [e.g., bariatric surgery or bowel resection]). Note, history of cholecystectomy is permitted if there is no evidence of malabsorption per the Investigator. A history of cancer or other malignancy, with the exception of low-grade cervical intraepithelial neoplasia, low-grade (low-risk) prostate cancer, or 5-year cancer-free survivors of basal or squamous cell carcinoma or higher-grade cervical intraepithelial neoplasia or prostate cancer. A positive test result for hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibody, or a human immunodeficiency virus (HIV) infection at Screening. Any clinically significant abnormalities in labs: biochemistry (including liver function test [LFT], estimated glomerular filtration rate [eGFR], and glucose), standard DocuSign Envelope ID: EB6849FB-17AD-4CBA-BC47-4D1BE77C1D88 CVN424Study No. CVN424-102Page 24of 64Clinical Protocol Version 1.030Aug2022hematology with white blood cell (WBC) differential, c-reactive protein (CRP), coagulation tests, lipase, amylase, albumin, and calcium. A supine blood pressure outside the ranges of 80 to 160 mm Hg for systolic and 50 to 100 mm Hg for diastolic, confirmed with up to two repeat tests at the Screening Visit; or symptomatic orthostatic hypotension, in the opinion of the Investigator. A resting heart rate outside the range of 40 to 100 beats per minute (bpm) confirmed with up to two repeat tests at the Screening Visit. Note that 40-50 and 90-100 bpm may be permitted only at the discretion of the Investigator. Positive urine result for illegal drugs at Screening and Check-In, or history of illicit drug use or alcohol abuse within 1 year prior to the Screening Visit. Received any investigational compound (defined as a drug that has not been FDA-approved) within 30 days prior to the first dose of study medication or within 5 half-lives of the investigational compound, whichever is greater. Within 14 or 28 days prior to randomization, ingested any of the following excluded medication, supplements, or food products: St. John's wort, ginseng, kava, Ginkgo biloba, Chinese herbs, and melatonin, or known strong inhibitors/inducers of cytochrome P-4503A4/5, including rifampin, clarithromycin, ketoconazole, itraconazole. For full list of prohibited medications and dietary products, (See Table 2 in full protocol). Regularly uses nicotine-containing products (including but not limited to cigarettes, electronic cigarettes, pipes, cigars, chewing tobacco, nicotine patch, or nicotine gum). The casual users (≤ 10 cigarettes/week) may participate; however, they must agree to refrain from 30 days before Day 0 (Inpatient Check-in) for the duration of the study or a positive urine cotinine test at Inpatient Check-in. Known history of coronary artery disease and hospitalization for myocardial infraction, ischemic heart disease, or congestive heart failure within the 2 years prior to the screening visit. Any clinically significant medical, psychiatric, or laboratory abnormality that, in the judgment of the Investigator, is likely to interfere with study participation A history of major depression or risk of suicide according to the Investigator's clinical judgment or has made a suicide attempt. Is a study site employee or an immediate family member of a study site employee
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Dr. Martin Bexon, MD
Organizational Affiliation
Cerevance Beta, Inc.
Official's Role
Study Chair
Facility Information:
Facility Name
Celerion
City
Tempe
State/Province
Arizona
ZIP/Postal Code
85283
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No

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Relative Bioavailability and Food Effect Study of CVN424

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