Clinical trial NCT06137703: A Study to Learn About the Study Medication, Zavegepant, in Healthy Volunteers
Official title: A PHASE 1, OPEN-LABEL, RANDOMIZED, 4-PERIOD, 4-WAY CROSSOVER, RELATIVE BIOAVAILABILITY STUDY OF ZAVEGEPANT (BHV-3500) ORAL FORMULATIONS UNDER FASTING CONDITIONS
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Biological Availability
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2023-11-18
Enrollment: 52
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Randomized, open-label, single dose, 4-period cross-over, comparative bioavailability study in healthy volunteer participants.
Primary purpose: BASIC_SCIENCE

Brief summary: This trial is designed to compare the rate and extent of absorption of four different formulations of zavegepant. 52 healthy male and female volunteers will receive a single dose of each formulation at least 7 days apart over a period of about 7 weeks and the amount of drug in their blood will be assessed over the 24 hour period after each dose.

Detailed description: This is a Phase 1, single centre, open-label, single dose, 4-period, crossover study designed to compare the pharmacokinetics (PK) of zavegepant from three Test products and a Reference product (treatment D).

52 male and female healthy volunteers will be randomly assigned to one of 4 treatment sequences: ACBD, CDAB, BADC, and DBCA.

In each period, subjects will receive one of the following: Treatment A, B, C, or D on Day 1, followed by 24 hours of PK and safety assessments. On Day 2 subjects will be discharged from the clinical site and instructed to return after at least a 7 day washout time has passed for subsequent periods of treatment.

The study will include a screening visit from Day -28 to Day -2. Eligible subjects will be admitted to the clinical site on Day -1 and will be confined until completion of the assessments on Day 2. There will be a washout period of at least 7 days between doses. Study Exit procedures will be performed after the last assessment on the morning of Day 2 of Period 4. Study Exit procedures will be performed as soon as possible in case of Early Termination.

The total duration of study participation for each subject from Screening through Study Exit is anticipated to be approximately 6.5 weeks.

Eligibility criteria: Inclusion Criteria:

* Participants must provide Informed Consent Form (ICF) obtained prior to the conduct of any study activities.
* Healthy Male or female participants at least 18 and less than 56 years of age,
* Participants must be Non-smokers and not have used any nicotine-containing products for 3 months prior to screening.
* Body Mass Index (BMI) \>18.5 and \<30.0kg/m2 and body weight ≥ 50.0kg for males and ≥ 45.0kg for females.
* All females participants must not be breastfeeding and have a negative urine pregnancy test at Screening.
* Females of childbearing potential must be willing to use acceptable contraceptive methods throughout the study and for 30 days after the last study drug administration.
* Male participants with a female partner of childbearing potential must be willing to use acceptable contraceptive methods from the first study drug administration until at least 90 days after the last study drug administration.

Exclusion Criteria:

* Current diagnosis of viral hepatitis or a history of liver disease.
* Any history of seizure disorder (e.g., epilepsy) other than a single childhood febrile seizure.
* Current or recent (within 3 months of the first study drug administration) gastrointestinal disease that may interfere with drug absorption.
* Prior gastrointestinal surgery that interferes with absorption and motility (e.g., gastric bypass, duodenectomy or gastric banding).
* History of drug or alcohol abuse.
* History of anaphylaxis, a documented hypersensitivity reaction, or a clinically significant reaction to any drug or to any of the excipient supporting the zavegepant formulations.
* Donation of plasma within 7 days prior to dosing, or donation or loss of blood (excluding volume drawn at Screening) of 50 mL to 499 mL of blood within 30 days, or more than 499 mL within 56 days prior to dosing.
* Participation in a clinical research study involving the administration of an investigational or marketed drug or device within 30 days prior to the dosing, extended to 90 days for biological products.
* Inability or difficulty to swallow tablets or capsules.
* Subjects with any clinically significant abnormality or significant abnormal laboratory test results found during medical screening or Day-1. Positive test for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), or hepatitis C virus (HCV) antibody during screening.
* Inadequate renal function - estimated glomerular filtration rate (eGFR) according to the Modification of Diet in Renal Disease (MDRD) study equation ≤ 60 mL/min/1.73 m2 at Screening.
* Any of the following laboratory parameters greater than the upper limit of normal (ULN) values at Screening or Baseline (Day -1): alkaline phosphatase (ALP) aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin, direct bilirubin, and indirect bilirubin, and alkaline phosphatase.
* Any clinically significant abnormalities on 12-lead ECG or blood pressure (BP) at Screening or Baseline (Day -1) visits.
* Any clinically significant abnormal haematological laboratory test values at Screening or Baseline (Day -1) visits.
* Positive test for COVID-19 performed on Day -1 of each period.

Primary outcomes:
measure: Area Under the Concentration-Time Curve From Time 0 to Infinity (AUCinf) of Zavegepant
timeFrame: Pre-dose, and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 16, and 24 hours post dose
measure: Maximum Observed Concentration (Cmax) of Zavegepant
timeFrame: Pre-dose, and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 16, and 24 hours post dose
measure: AUClast of Zavegepant
timeFrame: Pre-dose, and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 16, and 24 hours post dose
Secondary outcomes:
measure: Time to Reach Cmax (Tmax) of Zavegepant
timeFrame: Pre-dose, and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 16, and 24 hours post dose
measure: Terminal Phase Half-Life (t1/2) of Zavegepant
timeFrame: Pre-dose, and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 16, and 24 hours post dose
measure: Apparent Clearance (CL/F) of Zavegepant From Plasma
timeFrame: Pre-dose, and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 16, and 24 hours post-dose
measure: Apparent Volume of Distribution (Vz/F) of Zavegepant
timeFrame: Pre-dose, and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 16, and 24 hours post dose
measure: Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
timeFrame: Baseline up to study exit (approximately 6.5 weeks)
measure: Number of Participants With Clinically Significant Laboratory Abnormalities
timeFrame: Baseline up to study exit (approximately 6.5 weeks)
measure: Blood Pressure on Day -1 and Day 1 of Each Period
timeFrame: Day -1, pre-dose and 2 hours post dose on Day 1 of each period
measure: Blood Pressure at Screening and Study Exit
timeFrame: Screening and study exit
measure: Heart Rate (HR) on Day -1 and Day 1 of Each Period
timeFrame: Day -1, pre-dose and 2 hours post dose on Day 1 of each period
measure: HR at Screening and Study Exit
timeFrame: Screening and study exit
measure: Respiratory Rate (RR) on Day -1 of Each Period
timeFrame: Day -1 of each period
measure: RR at Screening and Study Exit
timeFrame: Screening and study exit
measure: Temperature on Day -1 of Each Period
timeFrame: Day -1 of each period
measure: Temperature at Screening and Study Exit
timeFrame: Screening and study exit
measure: Number of Participants With Clinically Significant Abnormal Electrocardiogram (ECG)
timeFrame: Screening up to study exit (approximately 6.5 weeks)
Other outcomes:
Locations:
city: Miami
country: United States
facility: Syneos Health Clinical Research Services, Llc
state: Florida
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: