A Study to Investigate the Effects of Sisunatovir on QTc Interval in Healthy Adult Participants.

Healthy Clinical Trial

Official title:

A Phase 1, Randomized, Double-blind, Sponsor-Open, Placebo- and Positive-Controlled Crossover Study to Investigate the Effect of Multiple Doses of Sisunatovir on QTc Interval in Healthy Adult Participants

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05878522
• Other study ID #: C5241015
• Status: Completed
• Phase: Phase 1
• Start date: May 15, 2023
• Est. completion date: October 30, 2023

Study information

• Verified date: February 2024
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of the study is to investigate the effects of multiple oral doses of sisunatovir on QTc Interval.

This study is seeking participants who:

• are male or female of 18 years of age or older

• are examined to be healthy All participants will receive Treatment A, B, and C in a randomized order based on 6 possible sequences. All treatments will be taken by mouth. Participants assigned to treatment A will receive 5 oral doses of sisunatovir administered Q12 hours over 3 days in a fed state. Participants assigned to treatment B will receive 5 oral doses of matching placebo administered Q12 hours over 3 days in a fed state. Participants assigned to treatment C will receive 4 oral doses of placebo administered Q12 hours for 2 days followed by a single dose of 400 mg moxifloxacin on the morning of Day 3.

All participants will remain in the study clinic for 4 days for each treatment, for safety review, laboratory collections, and to assess how the study medicine affects QTc intervals.

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 examined to see whether they are fit for the study. During this period, the participant's medical history and past and current medications will be reviewed. A series of tests will also be performed to see if they are good to be selected for the study. If the participant meets all required criteria and are interested in continuing, the participant will be brought into the study clinic to stay overnight for 4 days for each treatment. On day 4, the participant will be discharged. About 28 to 35 days after discharge 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 conclude the study.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 43
• Est. completion date: October 30, 2023
• Est. primary completion date: October 30, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria: for healthy volunteers:

• Body Mass Index (BMI) of 17.5 to 32 kg/m2, inclusive, and a total body weight >50 kg (110 lb).

• Capable of giving signed informed consent.

• At screening, no clinically relevant abnormalities identified by a detailed medical history, complete physical examination, including blood pressure (BP) and pulse rate measurement, standard 12-lead electrocardiogram (ECG) and clinical laboratory tests.

--Exclusion criteria for all participants:

• Any condition or surgery possibly affecting drug absorption (eg, prior bariatric surgery, gastrectomy, ileal resection)

• Those with increased risk if dosed with moxifloxacin

• Self-reported history or risk factors for QT prolongation or torsades de pointes, congenital deafness, family history of cardiac arrest or suggest death, and family history of long QT syndrome

• Positive human immunodeficiency virus (HIV) antibodies

• Positive drug or alcohol test

• Screening supine BP =140 mm Hg (systolic) or =90 mm Hg (diastolic), following at least 5 minutes of supine rest. If BP is =140 mm Hg (systolic) or =90 mm Hg (diastolic), 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-estimated glomerular filtration rate (GFR) <60 mL/min/1.73m2 at screening

• 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. Participants with an average QTc interval >450 milliseconds (ms) will not be allowed to participate in the study. Computer-interpreted ECGs should be overread by a physician experienced in reading ECGs before excluding a participant.

• GFR <60 mL/min/1.73m2 based on CKD-EPI equation

• AST or ALT level =1.5 x upper limit normal (ULN)

• Gamma-GT> 1.2 x ULN

• Alkaline phosphatase > 1.2 x ULN

• Total bilirubin level =1.5 × 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

• 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).

Related Conditions & MeSH terms

• Healthy

Intervention

Drug:
• sisunatovir
6 capsules administered Q12 hours for 5 doses
• placebo
6 capsules administered Q12 hours for 5 doses
• moxifloxacin
6 capsules of placebo administered Q12 hours for 4 doses, followed by a single tablet of moxifloxacin
• sisunatovir
7 capsules administered Q12 hours for 5 doses

Locations

Country	Name	City	State
United States	New Haven Clinical Research Unit	New Haven	Connecticut

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Evaluate sisunatovir's effect on the QTc interval (msec) by assessing concentration-QT (C-QT) relationship using exposure-response modeling	QTcF will be analyzed using concentration-QT (C-QT) modeling	On Day 3, Zero hour (prior to zero hour treatment administration), and at 0.25, 0.5, 1, 2, 3, 6, 12 and 24 hours post-dose
Secondary	Number of Participants With Treatment Emergent Treatment-Related Adverse Events (AEs)	Treatment-related AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. Serious adverse event (SAE) 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. Treatment-emergent are events between first dose of study drug and up to Y days after last dose that were absent before treatment or that worsened relative to pretreatment state. Relatedness to Drug X was assessed by the investigator (Yes/No). Participants with multiple occurrences of an AE within a category were counted once within the category.	Baseline (Day 0) up to 35 days after last dose of study medication
Secondary	Number of Participants With Clinically Significant Change From Baseline in Laboratory Abnormalities	Laboratory parameters included: hematology (hemoglobin, hematocrit, red blood cell, platelet and white blood cell count, neutrophils, eosinophils, monocytes, basophils and lymphocytes), chemistry (blood urea nitrogen, creatinine, sodium, potassium, aspartate aminotransferase, alanine aminotransferase, total bilirubin, alkaline phosphatase, albumin, total protein and serum pregnancy test [for all female participants]) and urine (urine pregnancy test [for all female participants]). Clinical significance of laboratory parameters was determined at the investigator's discretion.	Baseline up to Day 4
Secondary	Number of Participants With Clinically Significant Change From Baseline in Vital Signs	Vital signs (temperature, respiratory rate, pulse, systolic and diastolic blood pressure) were obtained with participant in the seated position, after having sat calmly for at least 5 minutes. Clinical significance of vital signs was determined at the investigator's discretion.	Baseline up to Day 4
Secondary	Time matched mean differences in QTc between moxifloxacin and placebo	Time matched mean differences in QTc between moxifloxacin and placebo at each post dose time point, including at the historical moxifloxacin Tmax of 3, 4, and 5 hours	On Day 3, zero hour (prior to zero hour treatment administration), and 1.5, 3, 4, 5, 6, 8, 12, and 24 hours post-dose

External Links

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