Clinical trial NCT05994963: A Study to Compare Different Preparations of Sisunatovir in Healthy Adult Participants.
Official title: A PHASE 1, RANDOMIZED, OPEN-LABEL, 2-PART CROSSOVER STUDY TO ASSESS THE RELATIVE BIOAVAILABILITY OF SISUNATOVIR FOLLOWING SINGLE ORAL DOSE OF DIFFERENT FORMULATIONS UNDER FED AND FASTED CONDITIONS IN HEALTHY ADULT PARTICIPANTS
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Keywords: Healthy Volunteers
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2023-08-16
Enrollment: 25
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Two Parts, Crossover study
Primary purpose: BASIC_SCIENCE

Brief summary: The purpose of this study is to learn how different preparations of sisunatovir are taken up into the blood when taken on an empty stomach or with a meal in healthy adults.

This study has two Parts and is seeking participants who:

- are healthy males or females of 18 years of age or older.

Part 1:

All participants will receive treatments: A, B, and C. The participants will be assigned to take medicines A, B or C by chance, like drawing names out of a hat.

All treatments will be taken by mouth.

* Participants assigned to treatment A will take four capsules of sisunatovir on empty stomach.
* Participants assigned to treatment B will take two sisunatovir tablets on empty stomach.
* Participants assigned to treatment C will take two sisunatovir tablets with a high-fat meal.

Part 2:

All participants will receive treatments: B and D. The participants will be assigned to take medicines B and D by chance, like drawing names out of a hat.

All treatments will be taken by mouth.

* Participants assigned to treatment B will take two sisunatovir tablets on empty stomach.
* Participants assigned to treatment D will take two sisunatovir tablets with a low-fat meal.

The participants will be in the study clinic for 10 days in Part 1 and 7 days in Part 2, for:

* safety checks,
* sample collection for lab tests,
* understanding how different preparations of sisunatovir are taken up into the blood when taken on an empty stomach or with a meal.

All participants selected in the study will be required to go through a screening period up to 28 days. A screening period is the time during which a few participants are tested to see whether they are fit for the study. The participants can join the study only if they are tested be fit and are interested to take part in the study.

The participants will be allowed to go home on Day 10 during Part 1, and on Day 7 during Part 2. About 28 to 35 days after being sent home following the final treatment, the participant will be contacted for a follow up visit either in person or by telephone. This is to check up on how the participant is doing and to end the study.


Eligibility criteria: Inclusion Criteria:

1. Participants aged 18 years of age or older, inclusive, at the time of signing of the informed consent document (ICD).

   • All fertile participants must agree to use a highly effective method of contraception.
2. Male and female participants who are overtly healthy as determined by medical evaluation including medical history, physical examination, laboratory tests, and cardiac evaluation.
3. Body mass index (BMI) of 18 to 32 kg/m2; and a total body weight \>45 kg (100 lb).

Exclusion Criteria:

1. Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurological, or allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at the time of dosing).

   * Any condition possibly affecting drug absorption (eg, gastrectomy, cholecystectomy).
   * History of HIV infection, hepatitis B, or hepatitis C; positive testing for HIV, HBsAg, or HCVAb. Hepatitis B vaccination is allowed.
2. Any medical or psychiatric condition including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormality or other conditions that may increase the risk of study participation or, in the investigator's judgment, make the participant inappropriate for the study.
3. Use of prescription or nonprescription drugs and dietary and herbal supplements within 7 days or 5 half-lives (whichever is longer) prior to the first dose of study intervention, with the exception of moderate/strong CYP3A inducers or time-dependent inhibitors which are prohibited within 14 days plus 5 half-lives prior to the first dose of study intervention
4. Previous administration with an investigational product (drug or vaccine) within 30 days (or as determined by the local requirement) or 5 half-lives preceding the first dose of study intervention used in this study (whichever is longer).
5. A positive urine drug test, confirmed by a repeated test, if deemed necessary.
6. For participants \<60 years: Screening supine BP ≥140 mm Hg (systolic) or

   * 90 mm Hg (diastolic), following at least 5 minutes of supine rest. For participants
   * 60 years old, a screening supine BP of ≥150/90 mm Hg may be used. If systolic BP is ≥ 140 or 150 mm Hg (based on age) or diastolic ≥90 mm Hg, the BP should be repeated 2 more times and the average of the 3 BP values should be used to determine the participant's eligibility.
7. Standard 12-lead ECG that demonstrates clinically relevant abnormalities that may affect participant safety or interpretation of study results (eg, QTcF \>450 ms, complete LBBB, signs of an acute or indeterminate- age myocardial infarction, ST-T interval changes suggestive of myocardial ischemia, second- or third- degree AV block, or serious bradyarrhythmias or tachyarrhythmias). If the uncorrected QT interval is \>450 ms, this interval should be rate-corrected using the Fridericia method only and the resulting QTcF should be used for decision making and reporting. If QTcF exceeds 450 ms, or QRS exceeds 120 ms, the ECG should be repeated twice and the average of the 3 QTcF or QRS values used to determine the participant's eligibility. Computer-interpreted ECGs should be overread by a physician experienced in reading ECGs before excluding a participant.
8. Participants with ANY of the following abnormalities in clinical laboratory tests at screening, as assessed by the study-specific laboratory and confirmed by a single repeat test, if deemed necessary:

   * eGFR \<60 mL/min/1.73m2 based on CKD-EPI equation; AST or ALT level ≥1.05× ULN;
   * GGT\>1.05× ULN;
   * ALP \>1.05× ULN;
   * Total bilirubin level ≥1.05× ULN; participants with a history of Gilbert's syndrome may have direct bilirubin measured and would be eligible for this study provided the direct bilirubin level is ≤ ULN.
9. History of alcohol abuse or binge drinking and/or any other illicit drug use or dependence within 6 months of Screening. Binge drinking is defined as a pattern of 5 (male) and 4 (female) or more alcoholic drinks in about 2 hours. As a general rule, alcohol intake should not exceed 14 units per week (1 unit = 8 ounces (240 mL) beer, 1 ounce (30 mL) of 40% spirit, or 3 ounces (90 mL) of wine).
10. History of sensitivity to sisunatovir or any of the formulation components.
11. Use of tobacco or nicotine-containing products in excess of the equivalent of 5 cigarettes/day or 2 chews of tobacco/day
12. Investigator site staff directly involved in the conduct of the study and their family members, site staff otherwise supervised by the investigator, and sponsor and sponsor delegate employees directly involved in the conduct of the study and their family members

Primary outcomes:
measure: Area Under the Concentration-Time Curve From Time Zero to The Time of The Last Quantifiable Concentration (AUClast) of Sisunatovir PIC Versus (vs) WGT in a Fasted State, Part 1
timeFrame: Pre-dose (0 hour), 1, 2, 3, 4, 5, 6, 8, 10,12 hours post-dose on Day 1; 24, 36 hours post-dose on Day 2; 48 hours post-dose on Day 3 of Period 1-3; 72 hours post-dose on Day 4 of period 3
measure: Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinite Time (AUCinf) of Sisunatovir PIC vs WGT in Fasted State, Part 1
timeFrame: Pre-dose (0 hour), 1, 2, 3, 4, 5, 6, 8, 10,12 hours post-dose on Day 1; 24, 36 hours post-dose on Day 2; 48 hours post-dose on Day 3 of Period 1-3; 72 hours post-dose on Day 4 of period 3
measure: Maximum Plasma Concentration (Cmax) of Sisunatovir PIC vs WGT in a Fasted State, Part 1
timeFrame: Pre-dose (0 hour), 1, 2, 3, 4, 5, 6, 8, 10,12 hours post-dose on Day 1; 24, 36 hours post-dose on Day 2; 48 hours post-dose on Day 3 of Period 1-3; 72 hours post-dose on Day 4 of period 3
Secondary outcomes:
measure: AUClast of Sisunatovir WGT Under Fasted vs With a High-fat Meal, Part 1
timeFrame: Pre-dose (0 hour), 1, 2, 3, 4, 5, 6, 8, 10,12 hours post-dose on Day 1; 24, 36 hours post-dose on Day 2; 48 hours post-dose on Day 3 of Period 1-3; 72 hours post-dose on Day 4 of period 3
measure: AUCinf of Sisunatovir WGT Under Fasted vs With a High-fat Meal, Part 1
timeFrame: Pre-dose (0 hour), 1, 2, 3, 4, 5, 6, 8, 10,12 hours post-dose on Day 1; 24, 36 hours post-dose on Day 2; 48 hours post-dose on Day 3 of Period 1-3; 72 hours post-dose on Day 4 of period 3
measure: Cmax of Sisunatovir WGT Under Fasted vs With a High-fat Meal, Part 1
timeFrame: Pre-dose (0 hour), 1, 2, 3, 4, 5, 6, 8, 10,12 hours post-dose on Day 1; 24, 36 hours post-dose on Day 2; 48 hours post-dose on Day 3 of Period 1-3; 72 hours post-dose on Day 4 of period 3
measure: AUClast of Sisunatovir WGT Under Fasted vs With a Low-fat Meal, Part 2
timeFrame: Pre-dose (0 hour), 1, 2, 3, 4, 5, 6, 8, 10,12 hours post-dose on Day 1; 24, 36 hours post-dose on Day 2; 48 hours post-dose on Day 3 of Period 1-3; 72 hours post-dose on Day 4 of period 3
measure: AUCinf of Sisunatovir WGT Under Fasted vs With a Low-fat Meal, Part 2
timeFrame: Pre-dose (0 hour), 1, 2, 3, 4, 5, 6, 8, 10,12 hours post-dose on Day 1; 24, 36 hours post-dose on Day 2; 48 hours post-dose on Day 3 of Period 1-3; 72 hours post-dose on Day 4 of period 3
measure: Cmax of Sisunatovir WGT Under Fasted vs With a Low-fat Meal, Part 2
timeFrame: Pre-dose (0 hour), 1, 2, 3, 4, 5, 6, 8, 10,12 hours post-dose on Day 1; 24, 36 hours post-dose on Day 2; 48 hours post-dose on Day 3 of Period 1-3; 72 hours post-dose on Day 4 of period 3
measure: Number of Participants With Treatment Emergent Adverse Events (TEAEs): Part 1
timeFrame: From start of study treatment on Day 1 up to 35 days after last dose of study drug (maximum up to 43 days)
measure: Number of Participants With Treatment Emergent Adverse Events (TEAEs): Part 2
timeFrame: From start of study treatment on Day 1 up to 35 days after last dose of study drug (maximum up to 39 days)
measure: Number of Participants With Clinically Significant Laboratory Abnormalities: Part 1
timeFrame: From start of study treatment on Day 1 up to 35 days after last dose of study drug (maximum up to 43 days)
measure: Number of Participants With Clinically Significant Laboratory Abnormalities: Part 2
timeFrame: From start of study treatment on Day 1 up to 35 days after last dose of study drug (maximum up to 39 days)
measure: Number of Participants With Clinically Significant Vital Signs Findings: Part 1
timeFrame: From start of study treatment on Day 1 up to 35 days after last dose of study drug (maximum up to 43 days)
measure: Number of Participants With Clinically Significant Vital Signs Findings: Part 2
timeFrame: From start of study treatment on Day 1 up to 35 days after last dose of study drug (maximum up to 39 days)
measure: Number of Participants With Clinically Significant 12-lead Electrocardiogram (ECG) Findings: Part 1
timeFrame: From start of study treatment on Day 1 up to 35 days after last dose of study drug (maximum up to 43 days)
measure: Number of Participants With Clinically Significant 12-lead Electrocardiogram (ECG) Findings: Part 2
timeFrame: From start of study treatment on Day 1 up to 35 days after last dose of study drug (maximum up to 39 days)
Other outcomes:
Locations:
city: Brussels
country: Belgium
facility: Pfizer Clinical Research Unit - Brussels
state: Bruxelles-capitale, Région DE
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: