Clinical trial NCT05635461: 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
Overall status: COMPLETED
Phase: PHASE1
Conditions: Parkinson's Disease
Lead sponsor: Cerevance
Sponsor class: INDUSTRY
First posted: 2022-12-02
Enrollment: 32
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

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, 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 for their next scheduled dosing period

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.
* 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), hematology 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.

Primary outcomes:
measure: Area Under the Concentration-time Curve From Time 0 to the Time of the Last Measured Non Zero Concentration (AUC0-t) of CVN424 Suspension Fasted and Tablet Fasted
timeFrame: Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60,72, 84 and 96 hours post-dose
measure: Area Under the Plasma Concentration Time Curve From Time 0 to 96 Hours (AUC 0-96h) of CVN424 Suspension Fasted and Tablet Fasted
timeFrame: Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60,72, 84 and 96 hours post-dose
measure: Maximum Observed Plasma Concentration (Cmax) of CVN424 Suspension Fasted and Tablet Fasted
timeFrame: Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60,72, 84 and 96 hours post-dose
measure: Time to Reach Cmax (Tmax) of CVN424 Suspension and Tablet
timeFrame: Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60,72, 84 and 96 hours post-dose
measure: Time Taken for Drug to Appear in Systemic Circulation Following Administration (Tlag) of CVN424 Suspension and Tablet
timeFrame: Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60,72, 84 and 96 hours post-dose
Secondary outcomes:
measure: AUC(0-t) of CVN424 Tablet Fed and Tablet Fasted
timeFrame: Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60,72, 84 and 96 hours post-dose
measure: AUC(0-96 Hrs) of CVN424 Tablet Fed and Tablet Fasted
timeFrame: Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60,72, 84 and 96 hours post-dose
measure: Cmax of CVN424 Tablet Fed and Tablet Fasted
timeFrame: Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60,72, 84 and 96 hours post-dose
measure: Tmax of CVN424 Tablet Fed and Tablet Fasted
timeFrame: Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60,72, 84 and 96 hours post-dose
measure: Tlag of CVN424 Tablet Fed and Tablet Fasted
timeFrame: Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60,72, 84 and 96 hours post-dose
measure: Number of Participants Reporting Treatment Emergent Adverse Events (TEAEs)
timeFrame: Up to Day 35
Other outcomes:
Locations:
city: Tempe
country: United States
facility: Celerion
state: Arizona
Study officials:
affiliation: Cerevance Beta, Inc.
name: Dr. Martin Bexon, MD
role: STUDY_CHAIR
References: