Relative Bioavailability and Food Effect Study of CVN424
Study Details
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1 |
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
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Active Comparator: Suspension (fasted) 150 milligrams (mg) of CVN424 administered in a single dose of suspension formulation. |
Drug: CVN424
150 mg of either tablet or suspension formulation
|
| Active Comparator: Tablet (fed) 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). |
Drug: CVN424
150 mg of either tablet or suspension formulation
|
| Active Comparator: Tablet (fasted) 150 milligrams (mg) tablet of CVN424 administered in a single dose. |
Drug: CVN424
150 mg of either tablet or suspension formulation
|
Outcome Measures
Primary Outcome Measures
- The relative bioavailability of the CVN424 solution and CVN424 tablet formulation in the fasted state. [Time 0 (time of dosing) to 96 hours post-dose for each treatment condition.]
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. [Time 0 (time of dosing) to 96 hours post-dose for each treatment condition.]
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 [Baseline through 30 days after study drug administration]
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).
Other Outcome Measures
- Characterization of metabolic enzyme and transporter polymorphisms [Baseline through 96 hours post dose of period 3 (overall study day 32)]
Plasma samples will be archived for potential analysis of metabolites.
- Characterization of metabolic enzyme and transporter polymorphisms [Baseline through 96 hours post dose of period 3 (overall study day 32)]
Plasma samples will be archived for potential analysis of target-related biomarkers.
- Characterization of metabolic enzyme and transporter polymorphisms [Baseline through 96 hours post dose of period 3 (overall study day 32)]
Urine samples will be archived for potential analysis of metabolites.
- Characterization of metabolic enzyme and transporter polymorphisms [Baseline through 96 hours post dose of period 3 (overall study day 32)]
Urine samples will be archived for potential analysis of target-related biomarkers.
- Calculation of urine PK parameters [Baseline through 96 hours post dose of period 3 (overall study day 32)]
Assessment of urine concentrations.
- Calculation of urine PK parameters [Baseline through 96 hours post dose of period 3 (overall study day 32)]
Assessment of urine volumes.
- Calculation of urine PK parameters [Baseline through 96 hours post dose of period 3 (overall study day 32)]
Assessment of cumulative amount of unchanged drug excreted into the urine.
- Calculation of urine PK parameters [Baseline through 96 hours post dose of period 3 (overall study day 32)]
Assessment of fraction of unchanged drug excreted in the urine.
- Calculation of urine PK parameters [Baseline through 96 hours post dose of period 3 (overall study day 32)]
Assessment of renal clearance.
Eligibility Criteria
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.
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The participant is male or female adult who is 18 to 55 years of age, inclusive at the time of Screening.
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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.
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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.
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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:
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Vegetarian, Vegan, Lactose intolerant, or follows a Kosher diet.
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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.
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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.
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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.
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A positive test result for hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibody, or a human immunodeficiency virus (HIV) infection at Screening.
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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.
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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.
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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.
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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.
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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.
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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).
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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.
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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.
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Any clinically significant medical, psychiatric, or laboratory abnormality that, in the judgment of the Investigator, is likely to interfere with study participation
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A history of major depression or risk of suicide according to the Investigator's clinical judgment or has made a suicide attempt.
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Is a study site employee or an immediate family member of a study site employee
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Celerion | Tempe | Arizona | United States | 85283 |
Sponsors and Collaborators
- Cerevance Beta, Inc.
Investigators
- Study Chair: Dr. Martin Bexon, MD, Cerevance Beta, Inc.
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- CVN424-102