A Study to Learn About the Study Medication, Zavegepant, in Healthy Volunteers

A PHASE 1, OPEN-LABEL, RANDOMIZED, 4-PERIOD, 4-WAY CROSSOVER, RELATIVE BIOAVAILABILITY STUDY OF ZAVEGEPANT (BHV-3500) ORAL FORMULATIONS UNDER FASTING CONDITIONS

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.

Study Overview

• Status: Completed
• Conditions: Biological Availability
• Intervention / Treatment: Drug: Zavegepant 100mg non-enteric coated soft gel capsule; Drug: Zavegepant 100mg immediate release tablet; Drug: Zavegepant 2 x 100mg immediate release tablets; Drug: Zavegepant 4 x 25mg enteric coated soft gel capsule

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.

• Study Type: Interventional
• Enrollment (Actual): 52
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Miami, Florida, United States, 33136
      • Syneos Health Clinical Research Services, LLC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sequence 1; Period 1 - Single zavegepant 100mg non-enteric coated soft gel capsule (Treatment A) followed by at least 7 days washout; Period 2 - Two zavegepant 100mg immediate release tablets (Treatment C) followed by at least 7 days washout; Period 3 - Single zavegepant 100mg immediate release tablet (Treatment B) followed by at least 7 days washout; Period 4 - Four zavegepant 25mg enteric coated soft gel capsule (Treatment D).	Drug: Zavegepant 100mg non-enteric coated soft gel capsule; Zavegepant (PF-07930207/BHV3500) 100mg non-enteric coated soft gel capsule; Other Names: Treatment A; Drug: Zavegepant 100mg immediate release tablet; Zavegepant (PF-07930207/BHV3500) 100mg dodecylmaltoside dosage form immediate release tablet; Other Names: Treatment B; Drug: Zavegepant 2 x 100mg immediate release tablets; 2 x Zavegepant (PF-07930207/BHV3500) 100mg dodecylmaltoside dosage form immediate release tablets - total dose 200mg; Other Names: Treatment C; Drug: Zavegepant 4 x 25mg enteric coated soft gel capsule; Zavegepant (PF-07930207/BHV3500) 25 mg enteric coated soft gel capsules - total dose 100mg; Other Names: Treatment D
Experimental: Sequence 2; Period 1 - Two zavegepant 100mg immediate release tablets (Treatment C) followed by at least 7 days washout; Period 2 - Four zavegepant 25mg enteric coated soft gel capsule (Treatment D) followed by at least 7 days washout; Period 3 - Single zavegepant 100mg non-enteric coated soft gel capsule (Treatment A) followed by at least 7 days washout; Period 4 - Single zavegepant 100mg immediate release tablet (Treatment B).	Drug: Zavegepant 100mg non-enteric coated soft gel capsule; Zavegepant (PF-07930207/BHV3500) 100mg non-enteric coated soft gel capsule; Other Names: Treatment A; Drug: Zavegepant 100mg immediate release tablet; Zavegepant (PF-07930207/BHV3500) 100mg dodecylmaltoside dosage form immediate release tablet; Other Names: Treatment B; Drug: Zavegepant 2 x 100mg immediate release tablets; 2 x Zavegepant (PF-07930207/BHV3500) 100mg dodecylmaltoside dosage form immediate release tablets - total dose 200mg; Other Names: Treatment C; Drug: Zavegepant 4 x 25mg enteric coated soft gel capsule; Zavegepant (PF-07930207/BHV3500) 25 mg enteric coated soft gel capsules - total dose 100mg; Other Names: Treatment D
Experimental: Sequence 3; Period 1 - Single zavegepant 100mg immediate release tablet (Treatment B) followed by at least 7 days washout; Period 2 - Single zavegepant 100mg non-enteric coated soft gel capsule (Treatment A) followed by at least 7 days washout; Period 3 - Four zavegepant 25mg enteric coated soft gel capsule (Treatment D) followed by at least 7 days washout; Period 4 - Two zavegepant 100mg immediate release tablets (Treatment C).	Drug: Zavegepant 100mg non-enteric coated soft gel capsule; Zavegepant (PF-07930207/BHV3500) 100mg non-enteric coated soft gel capsule; Other Names: Treatment A; Drug: Zavegepant 100mg immediate release tablet; Zavegepant (PF-07930207/BHV3500) 100mg dodecylmaltoside dosage form immediate release tablet; Other Names: Treatment B; Drug: Zavegepant 2 x 100mg immediate release tablets; 2 x Zavegepant (PF-07930207/BHV3500) 100mg dodecylmaltoside dosage form immediate release tablets - total dose 200mg; Other Names: Treatment C; Drug: Zavegepant 4 x 25mg enteric coated soft gel capsule; Zavegepant (PF-07930207/BHV3500) 25 mg enteric coated soft gel capsules - total dose 100mg; Other Names: Treatment D
Experimental: Sequence 4; Period 1 - Four zavegepant 25mg enteric coated soft gel capsule (Treatment D) followed by at least 7 days washout; Period 2 - Single zavegepant 100mg immediate release tablet (Treatment B) followed by at least 7 days washout; Period 3 - Two zavegepant 100mg immediate release tablets (Treatment C) followed by at least 7 days washout; Period 4 - Single zavegepant 100mg non-enteric coated soft gel capsule (Treatment A).	Drug: Zavegepant 100mg non-enteric coated soft gel capsule; Zavegepant (PF-07930207/BHV3500) 100mg non-enteric coated soft gel capsule; Other Names: Treatment A; Drug: Zavegepant 100mg immediate release tablet; Zavegepant (PF-07930207/BHV3500) 100mg dodecylmaltoside dosage form immediate release tablet; Other Names: Treatment B; Drug: Zavegepant 2 x 100mg immediate release tablets; 2 x Zavegepant (PF-07930207/BHV3500) 100mg dodecylmaltoside dosage form immediate release tablets - total dose 200mg; Other Names: Treatment C; Drug: Zavegepant 4 x 25mg enteric coated soft gel capsule; Zavegepant (PF-07930207/BHV3500) 25 mg enteric coated soft gel capsules - total dose 100mg; Other Names: Treatment D

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area Under the Concentration-Time Curve From Time 0 to Infinity (AUCinf) of Zavegepant	AUCinf was calculated as AUClast+(Clast*/kel), where AUClast is the area under the plasma concentration-time profile from time 0 to the time of the last quantifiable concentration, Clast* is the predicted plasma concentration at the last quantifiable time point estimated from the log-linear regression analysis, and kel is the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve. AUClast was calculated using Linear/Log trapezoidal method.	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
Maximum Observed Concentration (Cmax) of Zavegepant	Cmax was observed directly from data.	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
AUClast of Zavegepant	AUClast was calculated using linear/log trapezoidal method.	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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Reach Cmax (Tmax) of Zavegepant	Tmax was observed directly from data as time of first occurrence.	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
Terminal Phase Half-Life (t1/2) of Zavegepant	t1/2 was calculated as Log e(2)/kel, where kel is the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve.	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
Apparent Clearance (CL/F) of Zavegepant From Plasma	CL/F was calculated as dose/AUCinf. AUCinf was calucalted as AUClast+(Clast*/kel), where Clast* is the predicted plasma concentration at the last quantifiable time point estimated, and kel is the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve. AUClast was calculated using linear/log trapezoidal method.	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
Apparent Volume of Distribution (Vz/F) of Zavegepant	Vz/F was calculated by Dose/(AUCinf×kel). AUCinf was calculated by AUClast+(Clast*/kel), where Clast* is the predicted plasma concentration at the last quantifiable time point estimated from the log-linear regression analysis, and kel is the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve. AUClast was calculated using the linear/log trapezoidal method.	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
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)	Adverse evetn (AE)=any untoward medical occurrence in a patient or clinical trial participant administered a pharmaceutical product and which does not necessarily have a causal relationship with the treatment. TEAEs=AEs between first dose of study treatment and up to the end of study participation that were absent before treatment or that worsened relative to pretreatment state. A serious TEAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. SAEs were adjudicated according to the investigator's assessment. Treatment-related was classified based on medical judgement. Severe=Incapacitating with inability to carry out usual activities or significantly affects clinical status, and requires specific action and/or medical attention.	Baseline up to study exit (approximately 6.5 weeks)
Number of Participants With Clinically Significant Laboratory Abnormalities	Clinically significant laboratory abnormalities were identified as Grade 3 to 4 laboratory test results graded according to numeric laboratory test criteria in the latest version of Common Technical Criteria for Adverse Events (CTCAE) if available, otherwise according to the latest version of Division of Acquired Immunodeficiency Syndrome (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version. Clinically significant laboratory abnormalities with occurrence in at least 1 participant are reported for this outcome measure. Baseline was defined as the last results (scheduled or unscheduled) obtained prior to the first drug administration.	Baseline up to study exit (approximately 6.5 weeks)
Blood Pressure on Day -1 and Day 1 of Each Period	Blood pressure was measured after the participants had been resting for at least 5 minutes in a seated position. Normal range for systolic blood pressure (SBP)=90-140 mm Hg; normal range for diastolic blood pressure (DBP)=50-90 mm Hg.	Day -1, pre-dose and 2 hours post dose on Day 1 of each period
Blood Pressure at Screening and Study Exit	Blood pressure was measured after the participants had been resting for at least 5 minutes in a seated position. Normal range for SBP=90-140 mm Hg; normal range for DBP=50-90 mm Hg.	Screening and study exit
Heart Rate (HR) on Day -1 and Day 1 of Each Period	HR was measured after the participants had been resting for at least 5 minutes in a seated position. Normal range for heart rate=50-100 beats/min.	Day -1, pre-dose and 2 hours post dose on Day 1 of each period
HR at Screening and Study Exit	HR was measured after the participants had been resting for at least 5 minutes in a seated position. Normal range for heart rate=50-100 beats/min.	Screening and study exit
Respiratory Rate (RR) on Day -1 of Each Period	RR was measured after the participants had been resting for at least 5 minutes in a sitting position. Normal range for RR=8-20 breaths/min.	Day -1 of each period
RR at Screening and Study Exit	RR was measured after the participants had been resting for at least 5 minutes in a sitting position. Normal range for RR=8-20 breaths/min.	Screening and study exit
Temperature on Day -1 of Each Period	Temperature was measured after the participants had been resting for at least 5 minutes in a seated position. Normal range for temperature=35.8-37.6 ℃.	Day -1 of each period
Temperature at Screening and Study Exit	Temperature was measured after the participants had been resting for at least 5 minutes in a seated position. Normal range for temperature=35.8-37.6 ℃.	Screening and study exit
Number of Participants With Clinically Significant Abnormal Electrocardiogram (ECG)	ECG was measured after the participants had been resting for at least 5 minutes in a seated position.	Screening up to study exit (approximately 6.5 weeks)

Collaborators and Investigators

• Sponsor: Pfizer
• Investigators: Study Director: Pfizer CT.gov Call Center, Pfizer

Publications and helpful links

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start (Actual): August 24, 2022
• Primary Completion (Actual): December 7, 2022
• Study Completion (Actual): December 7, 2022

Study Registration Dates

• First Submitted: November 14, 2023
• First Submitted That Met QC Criteria: November 14, 2023
• First Posted (Actual): November 18, 2023

Study Record Updates

• Last Update Posted (Actual): October 1, 2024
• Last Update Submitted That Met QC Criteria: June 25, 2024
• Last Verified: June 1, 2024

More Information

Terms related to this study

• Other Study ID Numbers: BHV3500-113; C5301003 (Other Identifier: Alias Study Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.

Drug and device information, study documents

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