A phase 1 study of the breast milk and plasma pharmacokinetics of zavegepant 10 mg intranasal dose in healthy lactating women

Abstract

Objective

This study evaluated the pharmacokinetics of zavegepant in human breast milk and plasma following a single, 10 mg dose of zavegepant nasal spray.

Background

Zavegepant nasal spray is a member of the gepant class of medications; small molecule inhibitors of the calcitonin gene‐related peptide receptor. It is approved in the United States for the acute treatment of migraine with or without aura in adults. However, the transfer of zavegepant to human breast milk in lactating women has not been assessed previously.

Methods

In this Phase 1, open‐label, single‐arm, single‐dose, pharmacokinetic study (NCT06453356), 12 healthy lactating women received a single intranasal dose of 10 mg zavegepant. Blood and breast milk samples were collected over 24 h postdose to assess zavegepant pharmacokinetics. Safety was also assessed. The study was conducted from June 10 to September 26, 2024 at a single‐site in the United States.

Results

Geometric mean (geometric percent coefficient of variation [CV%]) milk‐to‐plasma zavegepant concentration ratios were 0.21 (102%), 0.16 (76%), and 0.04 (130%) for area under the concentration–time curve from time 0 to 24 h postdose, area under the concentration–time curve from time 0 extrapolated to infinity, and maximum concentration, respectively. The geometric mean (geometric CV%) body weight normalized infant dose was 0.05 μg/kg/day (120%) and the geometric mean (geometric CV%) body weight normalized maternal dose was 132.8 μg/kg/day (10%). This resulted in a geometric mean (geometric CV%) relative infant dose of 0.04% (128%). One treatment‐emergent adverse event (TEAE; mild dizziness) was reported in one (8%) participant. This TEAE was considered mild in severity. No clinically meaningful abnormalities were observed for vital signs, clinical laboratory testing, and local nasal assessments.

Conclusion

A single intranasal dose of 10 mg zavegepant was generally safe and well tolerated in healthy lactating women and the estimated infant exposure to zavegepant via breast milk is very low.

Plain Language Summary

Zavegepant is part of the gepant class of medications used to treat migraine in adults. The transfer of zavegepant to human breast milk in lactating women has not been assessed previously, so this study evaluated the amount of zavegepant in human breast milk following a single 10 mg dose of zavegepant nasal spray in healthy lactating women. The study found that this dose of zavegepant was generally safe and well tolerated, with very low estimated infant exposure to zavegepant through breast milk.

Abbreviations

AE

adverse event

AUC₂₄

area under the concentration–time profile from time 0 to 24 h post dose

AUC_inf

area under the concentration–time profile from time 0 extrapolated to infinite time

AUC_last

area under the concentration–time profile from time 0 to the time of the last quantifiable concentration

BMI

body mass index

C _max

maximum observed concentration

CV

coefficient of variation

IN

intranasal

PK

pharmacokinetic

SD

standard deviation

t _1/2

terminal half‐life

T _max

time to maximal concentration

INTRODUCTION

Migraine is the leading cause of years lived with disability among women 15–49 years of age. ¹ Although the frequency of migraine attacks may decrease during pregnancy, they typically resume within the first month following childbirth. ² , ³ Common treatments for the acute treatment of migraine include nonspecific analgesics (e.g., acetaminophen and nonsteroidal anti‐inflammatory drugs) for mild pain, and migraine‐specific agents (triptans and gepants) for moderate to severe pain. ⁴ , ⁵ Gepants are a novel class of medications that act as antagonists to the calcitonin gene‐related peptide receptor. ⁶ Currently, gepants are approved for the acute (rimegepant, ubrogepant, and zavegepant) or preventive (atogepant and rimegepant) treatment of migraine.

An intranasal (IN) formulation of zavegepant is the first and only calcitonin gene‐related peptide receptor antagonist nasal spray approved in the United States for the acute treatment of migraine (with or without aura) in adults. ⁷ Peak plasma zavegepant concentrations are reached approximately 30 min after a single 10 mg IN dose, with an absolute bioavailability of 5%. ⁷ Single dose IN zavegepant displays slightly less than dose‐proportional pharmacokinetics (PK) up to 40 mg (approximately four times the recommended dose of 10 mg). ⁷ There is no evidence of zavegepant accumulation following once‐daily dosing for 14 days. ⁷ Zavegepant is excreted mostly via the biliary/fecal route, whereas the renal route is a minor route of elimination. ⁷ Oxidative metabolism is a minor pathway of zavegepant elimination that is primarily mediated by cytochrome P450 3A4 with minor contribution from cytochrome P450 2D6. ⁷ , ⁸ Zavegepant intravenous clearance, steady‐state volume of distribution, and terminal half‐life are 13.2 L/h, 41.6 L, and 6.8 h, respectively. ⁷ , ⁸ Concomitant administration of zavegepant with inhibitors of organic anion transporting polypeptide 1B3 (OATP1B3) or sodium taurocholate cotransporting polypeptide can increase zavegepant exposure and should be avoided. ⁷ , ⁹ Conversely, concomitant administration of zavegepant with inducers of OATP1B3 or sodium taurocholate cotransporting polypeptide may decrease zavegepant exposure and should be avoided. ⁷

Although there are lactation data available for rimegepant, ubrogepant, and atogepant, there are no lactation data currently available for zavegepant. ¹⁰ , ¹¹ , ¹² This lack of data may cause concern regarding infant exposure and could result in the mother avoiding breastfeeding while on zavegepant or avoidance of migraine therapy with zavegepant while breastfeeding. ¹³ , ¹⁴ , ¹⁵ Therefore, the primary objective of this study was to evaluate the PK of zavegepant in human breast milk following a single 10 mg IN dose of zavegepant in lactating women as described by the primary end point measurements of area under the concentration–time profile from time 0 extrapolated to infinite time (AUC_inf), area under the concentration–time profile from time 0 to the time of the last quantifiable concentration (AUC_last), area under the concentration–time profile from time 0 to 24 h post dose (AUC₂₄), maximum observed concentration (C _max), time to maximal concentration (T _max), and terminal half‐life (t _1/2) of zavegepant in breast milk. Secondary objectives were to characterize plasma PK parameters, to estimate the milk‐to‐plasma drug concentration ratio, and to characterize the safety of a single 10 mg IN dose of zavegepant in lactating women. The infant dose resulting from zavegepant secretion in breast milk following a single 10 mg IN dose was estimated as an exploratory tertiary objective.

METHODS

Study design

This was a single‐site, phase 1, open‐label, single‐arm, single‐dose, PK study in healthy lactating women (NCT06453356) conducted at Bio‐Kinetic Clinical Applications, LLC dba QPS‐MO (Springfield, MO, USA) from June 10, 2024, to September 26, 2024. Participants were screened within 28 days before study treatment, were admitted to the study site on day −1, received study treatment on day 1, had blood and breast milk samples taken over 24 h postdose, were discharged on day 2, and had a telephone follow‐up 28–35 days after dosing (Figure 1).

FIGURE 1.

Overview of study design. Healthy lactating women received a single dose of 10 mg IN zavegepant on Day 1. Breast milk samples were collected before dosing on day 1 and at 0–2, 2–4, 4–6, 6–8, 8–12, 12–16, and 16–24 h postdose. Venous blood samples were collected before dosing on day 1 and at 15, 30 min, 1, 2, 4, 6, 8, 12, and 24 h postdose. IN, intranasal.

The study protocol was approved (protocol approval no. Pro00078892) by Advarra, Inc. (Columbia, MD, USA) on April 22, 2024. All participants provided written informed consent. The study was conducted in compliance with ethical principles of the Declaration of Helsinki and all International Conference on Harmonization Good Clinical Practice Guidelines.

Participants

Participants were healthy lactating women 18–55 years of age (with or without a history of acute migraine) who were actively breastfeeding or expressing breast milk, at least 2 weeks post‐partum, and not currently pregnant. Participants must have been able to express at least 14 mL of breast milk over a 2‐hour interval before dosing on day 1. Participants were not actively treating an acute migraine attack during their participation in the study. Other inclusion criteria included a body mass index (BMI) of 16.0–34.9 kg/m², a body weight ≥45.0 kg, a willingness to temporarily discontinue breastfeeding their infants for a total of 2.5 days (from the evening before day 1 through the morning of day 3), and a willingness to regularly pump breasts throughout the study and express breast milk according to a schedule designed to maintain lactation throughout the study period. Participants were not allowed to feed infants any breast milk expressed following zavegepant administration (through 48 h postdose) and, as such, had to be able to successfully feed formula or previously expressed breast milk from a bottle or another age‐appropriate method. A full list of exclusion criteria is provided in Table S1.

Study treatment

Site staff administered a single 10 mg dose of zavegepant nasal spray into one nostril of participants at approximately 8:00 a.m. on day 1. Participants were observed and asked to remain seated upright for approximately 10 min following dosing, and to inform the staff if they sneezed or product dripped out of their nose either during or shortly after the administration.

Prior and concomitant treatments

Concomitant administration of zavegepant with inhibitors of OATP1B3 was prohibited. The use of prescription medications (except for hormonal contraception) and nasal spray decongestants was prohibited within 14 days before dosing of study treatment until the last PK blood sample collection of the study. The use of over‐the‐counter products was prohibited within 7 days before dosing of study treatment through the end of the study. Depot injections or implants of any drug (other than hormonal contraceptives) were prohibited within 3 months before dosing of study medication. Natural health products were prohibited within 7 days before dosing of study medication until collection of the last PK blood sample.

Participants refrained from all food and drink (except water) at least 4 h before safety laboratory evaluations. Lunch and dinner were provided at appropriate times. Participants refrained from consuming red wine, grapefruit, or grapefruit‐related citrus fruits from 7 days before dosing of study treatment until collection of the final PK blood sample. Participants refrained from caffeine from 24 h before dosing of study treatment until collection of the final PK blood sample. Participants refrained from alcohol for 24 h before admission to the study site until collection of the final PK sample.

Assessments

Breast milk samples were collected to assess zavegepant PK before dosing on day 1 and at 0–2, 2–4, 4–6, 6–8, 8–12, 12–16, and 16–24 h postdose. Venous blood samples (approximately 4 mL to provide approximately 1.5 mL of plasma) were collected to assess zavegepant PK before dosing on day 1 and at 15, 30 min, 1, 2, 4, 6, 8, 12, and 24 h postdose. Extracted samples were analyzed for zavegepant concentrations by liquid chromatography coupled with tandem mass spectrometry using positive ionization mode of the AB Sciex API 5000 mass spectrometer. The chromatographic separation was achieved using an Avantor Excel 2 C18‐ PFP, 50 × 3.0 mm, 2 μm column, and isocratic elution.

Safety assessments included nasal inspections (at admission and discharge), vital signs (at screening, predose on day 1, and at discharge), clinical laboratory assessments (at screening, admission, and discharge), and adverse event (AE) reporting throughout the study. AEs were coded using Medical Dictionary for Regulatory Activities v27.0, with severity and relationship to study treatment determined by the site investigator.

End points and analysis

There was no statistical hypothesis for this study and no statistical power calculation was conducted before the study. A sample size of 12 participants was chosen based on it being considered sufficient for characterizing the central tendencies of zavegepant PK and it being consistent with the sample size of similar lactation PK studies. ¹⁰ , ¹¹ Zavegepant concentrations were assessed, using validated bioanalytical assays, in all participants who received one dose of study treatment and provided one or more evaluable plasma or breast milk concentration (PK concentration population). The lower limit of quantification was 40.0 pg/mL for the plasma assay and 5.0 pg/mL for the breast milk assay. For breast milk, the concentration–time profile consists of the observed concentrations and the midpoints for each collection interval. Mean concentration–time profiles were generated for zavegepant in plasma and in breast milk. Values below the lower limit of concentration (5.0 pg/mL for breast milk and 40.0 pg/mL for plasma) were set to 0. Zavegepant PK parameters including C _max, AUC_last, AUC_inf, AUC₂₄, T _max, t _1/2, and average concentration (in plasma only) were determined by standard noncompartmental methods (Table S2) using a validated Pfizer open noncompartmental analysis system (oNCA, version 2.7.8). PK parameters were summarized descriptively in all participants who received a single dose of study treatment and provided one or more evaluable PK parameter of interest in plasma or breast milk (PK parameter population). Summaries included geometric mean (geometric CV%) and median (min, max) values for each parameter, except for t _1/2 (mean [SD] and median [min, max]) and T _max (median [min, max]). Per US Food and Drug Administration guidance, breast milk‐to‐plasma concentration ratios were estimated for AUC₂₄, AUC_inf, and C _max. ¹⁶ Parameters for estimation of body weight normalized infant dose, body weight normalized maternal dose, and relative infant dose were also determined as described in detail in Table S3. ¹⁶ Briefly, relative infant dose was determined by multiplying the ratio of the body weight normalized infant dose (BWNID) to the body weight normalized maternal dose (BWNMD) by 100 (i.e., 100*[BWNID/BWNMD]). Summaries for BWNID, BWNMD, and relative infant dose included geometric mean (geometric CV%) and median (min, max) values for each parameter.

Safety and tolerability end points (AEs, vital signs, clinical laboratory testing, and local nasal assessments) were summarized descriptively in all participants who received study treatment (safety population). Summaries included the n (%) of participants or mean (SD) and median (min, max) values.

This article presents the initial (primary) analysis of the data from this study and all analyses were prespecified in the statistical analysis plan and study protocol.

RESULTS

A total of 12 women were screened and received a single IN dose of 10 mg zavegepant. All 12 treated participants were included in the PK concentration, PK parameter, and safety analyses (Figure 2). The study population had a mean (SD) age of 29.3 (5.5) years, a mean (SD) BMI of 28.8 (3.8) kg/m², and was mostly White (83%) (Table 1). One participant used a concomitant medication during the study (norethindrone, not related to the treatment of an AE).

FIGURE 2.

Summary of participant disposition during the study. PK, pharmacokinetic.

TABLE 1.

Summary of demographics of healthy lactating women receiving a single 10 mg intranasal dose of zavegepant (n = 12).

Demographic	Value
Age, years
Mean (SD)	29.3 (5.5)
Median (min, max)	29.0 (20, 39)
Race, n (%)
White	10 (83)
Black or African American	1 (8)
American Indian or Alaska Native	1 (8)
Ethnicity, n (%)
Hispanic or Latino	2 (17)
Not Hispanic or Latino	10 (83)
BMI, kg/m2
Mean (SD)	28.8 (3.8)
Median (min, max)	29.7 (20.1, 34.8)

Abbreviations: BMI, body mass index; SD, standard deviation.

Mean zavegepant concentration–time profiles following a single 10 mg IN administration in healthy lactating women are shown for breast milk and plasma in Figure 3 and Table S4. The number of participants with available concentration data in breast milk was two at 0–2 h (all participants had quantifiable concentrations but 10 participants had a time deviation >20% for the end of the allowed collection interval and were excluded from the summary), 10 at 2–4 h, and 12 at all other time points. The number of participants with available concentration data in plasma was 11 at 15 and 30 min, and 12 at all other time points.

FIGURE 3.

Summary of mean zavegepant concentrations over time in breast milk and plasma following a single 10‐mg intranasal dose in healthy lactating women. Mean zavegepant concentrations in breast milk (red) and plasma (blue) are shown following a single 10 mg intranasal dose in healthy lactating women. Zavegepant concentrations in breast milk were assessed predose (0 h) and at 0–2, 2–4, 4–6, 6–8, 8–12, 12–16, and 16–24 h postdose. Zavegepant concentrations in plasma were assessed predose (0 h) and at 15 min, 30 min, 1, 2, 4, 6, 8, 12, and 24 h postdose. Values below the lower limit of concentration (5.0 pg/mL for breast milk and 40.0 pg/mL for plasma) were set to 0. The number of participants with available concentration data in breast milk was 2 at 0–2, 10 at 2–4, and 12 h at all other time points. The number of participants with available concentration data in plasma was 11 at 15 and 30 min, and 12 at all other time points.

Zavegepant PK parameters in human milk and plasma are shown in Table 2. The number of participants contributing (data available) to each PK parameter in each matrix was 12, except for AUC_inf and t _1/2 (n = 6 for each) in breast milk; due to a half‐life of 5–7 h for milk concentrations, the terminal phase of zavegepant elimination in milk could not be reliably estimated for six of the 12 participants. Both matrices showed high variability (CV%) in estimation of AUC parameters (96%–120% in breast milk and 119%–120% in plasma) and C _max (132% in breast milk and 110% in plasma). Geometric mean (geometric CV%) milk‐to‐plasma concentration ratios were 0.21 (102%), 0.16 (76%), and 0.04 (130%) for AUC₂₄, AUC_inf, and C _max, respectively, revealing a significantly lower exposure of zavegepant in breast milk compared to plasma (Table 2). The geometric mean (geometric CV%) body weight normalized infant dose was 0.05 μg/kg/day (120%) and the geometric mean (geometric CV%) body weight normalized maternal dose was 132.8 μg/kg/day (10%) (Table 3). This resulted in a geometric mean (geometric CV%) relative infant dose of 0.04% (128%).

TABLE 2.

Summary of zavegepant pharmacokinetic parameters in breast milk and plasma following a single 10 mg intranasal dose in healthy lactating women.

Parameter, unit	Sample matrix		Breast milk:plasma ratio
	Breast milk a	Plasma b
AUC24, ng × h/mL
Geometric mean (geometric CV%)	7.89 (120)	37.90 (120)	0.21 (102)
Median (min, max)	9.19 (1.13, 30.7)	26.35 (10.3, 264)	0.17 (0.08, 1.29)
AUCinf, ng × h/mL
Geometric mean (geometric CV%)	5.01 (96)	39.24 (119)	0.16 (76)
Median (min, max)	6.37 (1.28, 10.7)	27.50 (10.7, 269)	0.14 (0.09, 0.61)
AUClast, ng × h/mL
Geometric mean (geometric CV%)	7.09 (116)	37.90 (120)	Not determined
Median (min, max)	8.55 (1.04, 27.5)	26.35 (10.3, 264)	Not determined
C av, ng/mL
Geometric mean (geometric CV%)	Not determined	1.64 (118)	Not determined
Median (min, max)	Not determined	1.15 (0.45, 11.2)	Not determined
C max, ng/mL
Geometric mean (geometric CV%)	0.77 (132)	18.41 (110)	0.04 (130)
Median (min, max)	1.10 (0.10, 2.34)	15.20 (3.85, 92.5)	0.03 (0.01, 0.27)
t 1/2, h
Mean (SD)	6.37 (0.80)	7.63 (0.62)	Not determined
Median (min, max)	6.49 (5.21, 7.53)	7.51 (6.31, 8.48)	Not determined
T max, h
Median (min, max)	4.83 (0.73, 13.7)	0.50 (0.25, 1.00)	Not determined

Abbreviations: AUC₂₄, area under the concentration‐time curve from time 0 to 24 h; AUC_inf, area under the concentration–time curve from time 0 extrapolated to infinity; AUC_last, area under the concentration–time curve from time 0 to the time of the last quantifiable concentration; C _av, average concentration; C _max, maximum concentration; CV, coefficient of variation; t _1/2, terminal half‐life; SD, standard deviation; T _max, time to maximum concentration.

^a The number of participants contributing (data available) to each parameter was 12 except for AUC_inf and t _1/2 (n = 6 for each). Because of a half‐life of 5–7 h for milk concentrations, the terminal phase of zavegepant elimination in milk could not be reliably estimated for 6 of 12 participants.

^b The number of participants contributing (data available) to each parameter was 12.

TABLE 3.

Estimation of body weight normalized infant dose, body weight normalized maternal dose, and relative infant dose.

Parameter, unit	Value
Body weight normalized infant dose, μg/kg/day
Geometric mean (geometric CV%)	0.05 (120)
Median (min, max)	0.06 (0.01, 0.20)
Body weight normalized maternal dose, μg/kg/day
Geometric mean (geometric CV%)	132.8 (10)
Median (min, max)	131.0 (108, 163)
Relative infant dose, %
Geometric mean (geometric CV%)	0.04 (128)
Median (min, max)	0.05 (0.01, 0.18)

Note: The number of participants contributing (data available) to each parameter was 12.

Abbreviation: CV, coefficient of variation.

One AE (dizziness) was reported in one (8%) participant. This AE was considered mild in severity and did not require interventional treatment. No clinically meaningful abnormalities were observed for vital signs, clinical laboratory testing, and local nasal assessments.

DISCUSSION

Migraine is common in women of childbearing age, and postpartum breastfeeding women with a history of migraine are likely candidates for pharmacologic therapy. ¹ A variety of gepant‐class medications are approved for acute and/or preventive treatment of migraine (oral atogepant, oral rimegepant, oral ubrogepant, and zavegepant nasal spray), and lactation data are available for oral rimegepant, atogepant, and ubrogepant. ¹⁰ , ¹¹ , ¹² This study, therefore, evaluated the concentration of zavegepant, the first and only nasal spray in the gepant class approved for acute treatment of migraine with and without aura, in maternal plasma and breast milk of healthy lactating women.

Zavegepant exposures observed in healthy lactating females following a single 10 mg IN dose in the current study (geometric mean AUC_inf = 39.24 ng × h/mL and geometric mean C _max = 18.41 ng/mL) are comparable to exposures observed following a single 10 mg IN dose in previous studies of healthy adults and patients with migraine. ⁹ , ¹⁷ , ¹⁸ , ¹⁹ Following a single 10 mg IN administration to healthy lactating women in the current study, zavegepant concentrations were detectable in breast milk at all postdose time points up to 24 h. However, geometric mean milk‐to‐plasma concentration ratios were low (0.04–0.21) based on assessments of AUC₂₄, AUC_inf, and C _max, and the relative infant dose was estimated at <0.1% of the maternal dose. Thus, infant exposure to zavegepant via breast milk is expected to be low. Zavegepant was also well tolerated in healthy lactating women.

Overall, these findings with 10 mg IN zavegepant nasal spray are consistent with previous findings for a 75 mg dose of oral rimegepant, a 100 mg dose of oral ubrogepant, or a 60 mg dose of oral atogepant in healthy lactating women, where the relative infant doses of rimegepant, ubrogepant, and atogepant were estimated at <1%. ⁹ , ¹⁰ , ¹¹ , ¹² A relative infant dose <5%–10% is typically cited as a common safety threshold. ¹⁰ Findings with rimegepant, ubrogepant, atogepant, and zavegepant, therefore, indicate that these agents are well tolerated in healthy lactating women and infant exposure via breast milk is low.

A key limitation of this study is the small sample size, particularly with regard to safety. Sample size was generally considered sufficient for characterizing the central tendencies of zavegepant PK and was consistent with sample sizes in similar lactation PK studies. ¹⁰ , ²⁰ High inter‐individual variability was observed in PK parameters and the derived milk:plasma ratios, affecting the precision of these estimates. Despite high variability, and resulting wide range of estimated infant doses, the upper range of the relative infant dose was well below 10% (a threshold commonly cited for infant safety). ¹⁰ , ¹¹ , ²¹ Finally, the study required participants to discard breast milk collected after administration of zavegepant and infants were not directly exposed to zavegepant. Therefore, safety conclusions in infants are inferential, based on the safety in mothers and low estimated infant exposure. The key strength of this study is that it is the first to evaluate the PK of zavegepant in lactating women and confirms the minimal transfer of this medicine into human breast milk.

The study also adds to the scientific literature for lactation data involving the gepant class of anti‐migraine medications. Overestimation of infant exposure to prescribed therapies may cause breastfeeding women to either avoid breastfeeding (causing the child missing out on the myriad benefits of breastfeeding) or avoid treatment (causing the mother to experience the physical and emotional impacts of untreated migraine). ¹³ , ¹⁴ , ¹⁵ Studies such as ours help quantify infant exposure via breast milk and may help to educate mothers and prescribers to optimize migraine therapy during lactation.

CONCLUSIONS

This phase 1, open‐label study demonstrates that a single IN dose of 10 mg zavegepant is well tolerated in healthy lactating women and that the estimated infant exposure to zavegepant via breast milk is very low. The favorable safety profile of zavegepant observed in this study and in previous adult studies, along with very low infant exposure, supports the safe use of zavegepant by lactating women with migraine.

AUTHOR CONTRIBUTIONS

Abhijeet Jakate: Investigation; methodology; project administration; supervision; writing – review and editing. Yan Weng: Conceptualization; writing – review and editing. Ani Shkrodova: Conceptualization; investigation; supervision; writing – review and editing. Ogert Fisniku: Writing – review and editing; data curation. Ding Ding: Writing – review and editing; formal analysis. Kayce Morton: Investigation; writing – review and editing. Benjamin Maligalig: Writing – review and editing; methodology; formal analysis. Pamela Garnick: Writing – review and editing; conceptualization; methodology; project administration; supervision. Jing Liu: Writing – review and editing; conceptualization; methodology; supervision. Mohamed H. Shahin: Writing – review and editing; conceptualization; investigation; methodology; supervision.

FUNDING INFORMATION

This study was sponsored by Pfizer.

CONFLICT OF INTEREST STATEMENT

Abhijeet Jakate, Yan Weng, Ani Shkrodova, Ogert Fisniku, Ding Ding, Benjamin Maligalig, Pamela Garnick, Jing Liu, and Mohamed H. Shahin are employees of, and own stock/options in, Pfizer. Kayce Morton has no potential conflicts of interest to declare.

CLINICAL TRIALS REGISTRATION NUMBER

Clinicaltrials.gov number: NCT06453356.

Supporting information

Table S1.

Table S2.

Table S3.

Table S4.

DATA AVAILABILITY STATEMENT

On request, and subject to review, Pfizer will provide the data that support the findings of this study. Pursuant to certain criteria, conditions, and exceptions, Pfizer may also provide access to the related individual de‐identified participant data. For more information, go to https://www.pfizer.com/science/clinical‐trials/trial‐data‐and‐results.