Clinical trial NCT05878522: A Study to Investigate the Effects of Sisunatovir on QTc Interval in Healthy Adult Participants.
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Keywords: Healthy volunteers
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2023-05-26
Enrollment: 43
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Single Group, Crossover study
Primary purpose: BASIC_SCIENCE

Brief 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.


Eligibility criteria: 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).

Primary outcomes:
measure: Placebo-Adjusted Change From Baseline in QT Interval Corrected Using Fridericia's Formula (QTcF) at Expected Maximum Concentration (Cmax) on Day 3 for Sisunatovir
timeFrame: Baseline, Day 3
Secondary outcomes:
measure: Number of Participants With Treatment Emergent Adverse Events
timeFrame: From start of treatment on Day 1 up to 38 days after last dose of study drug (maximum up to 10 weeks)
measure: Number of Participants With Clinically Significant Changes in Electrocardiogram Parameters
timeFrame: From Baseline up to Day 23
measure: Number of Participants Meeting Pre-defined Criteria for Vital Signs
timeFrame: From Baseline up to Day 23
measure: Number of Participants With Clinically Significant Changes in Laboratory Abnormalities
timeFrame: From Baseline up to Day 23
measure: Change From Baseline in QTcF of Moxifloxacin and Placebo at 3, 4 and 5 Hours Post-Dose of Day 3
timeFrame: Baseline, 3, 4 and 5 hours post-dose on Day 3
Other outcomes:
Locations:
city: New Haven
country: United States
facility: New Haven Clinical Research Unit
state: Connecticut
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: