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Evaluation of the Effect of Benzonatate on QT Intervals Following Single Dose Administration of Benzonatate to Healthy Volunteers

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02207699
Recruitment Status : Completed
First Posted : August 4, 2014
Last Update Posted : August 4, 2014
Sponsor:
Information provided by (Responsible Party):
Pfizer

Brief Summary:
The primary objective of this study is to determine the effects of benzonatate (200 mg and 800 mg) on the QT interval following single dose oral administration at each time point post-dose.

Condition or disease Intervention/treatment Phase
Healthy Volunteers Drug: Benzonatate 200 mg Drug: Benzonatate 800 mg Drug: Moxifloxacin 400 mg Drug: Placebo Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 68 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Basic Science
Official Title: Evaluation of the Effect of Benzonatate on QT Intervals Following Single Dose Administration of Benzonatate to Healthy Volunteers
Study Start Date : May 2014
Actual Primary Completion Date : July 2014
Actual Study Completion Date : July 2014

Resource links provided by the National Library of Medicine

Drug Information available for: Benzonatate

Arm Intervention/treatment
Experimental: Benzonatate 200 mg Drug: Benzonatate 200 mg
2 benzonatate 100 mg perles and 6 placebo perles give by mouth once

Experimental: Benzonatate 800 mg Drug: Benzonatate 800 mg
8 benzonatate 100 mg perles given by mouth once

Active Comparator: Moxifloxacin 400 mg Drug: Moxifloxacin 400 mg
1 moxifloxacin 400 mg tablet given by mouth once

Placebo Comparator: Placebo Drug: Placebo
8 placebo perles given by mouth once




Primary Outcome Measures :
  1. Fridericia-corrected QTc change from the pre-dose time point to the post-dose time points following administration of study drug in therapeutic (200 mg) and supratherapeutic doses (800 mg). [ Time Frame: -1, -0.75, -0.5, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 12, and 24 hours ]

Secondary Outcome Measures :
  1. QT interval for Benzonatate, 4-(butylamino)benzoic acid (BBA-major metabolite of benzonatate), and moxifloxacin. [ Time Frame: -1, -0.75, -0.5, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 12, and 24 hours ]
  2. PR interval, QRS complex from single 12-lead electrocardiogram (ECG) [ Time Frame: Screening, Day 0, and Day 1 at 4, 8, and 24 hours after dosing ]
  3. Cmax (maximum plasma concentration) for BT and BBA measured in mcg/mL [ Time Frame: 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, and 12 hours ]
  4. Tmax (time of maximum plasma concentration) for BT and BBA measured in minutes [ Time Frame: 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, and 12 hours ]
  5. t½ (terminal half-life) for BT and BBA measured in minutes [ Time Frame: 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, and 12 hours ]
  6. AUClast for BT and BBA measured in mcg•hr/mL [ Time Frame: 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, and 12 hours ]
  7. AUCinf for BT and BBA measured in mcg•hr/mL [ Time Frame: 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, and 12 hours ]
  8. Cmax(dn) for BT and BBA measured in mcg/mL [ Time Frame: 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, and 12 hours ]
  9. AUClast(dn) for BT and BBA measured in mcg•hr/mL [ Time Frame: 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, and 12 hours ]
  10. AUCinf(dn) for BT and BBA measured in mcg•hr/mL [ Time Frame: 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, and 12 hours ]
  11. CL/F for BT measured in L/hr [ Time Frame: 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, and 12 hours ]
  12. Vz/F for BT measured in L [ Time Frame: 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, and 12 hours ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Healthy male and female subjects between the ages of 18 and 55 years, inclusive. Healthy is defined as no clinically relevant abnormalities identified by a detailed medical history, full physical examination, including blood pressure and pulse rate measurement, 12- lead ECG and clinical laboratory tests.
  • Female subjects of non-childbearing potential must meet at least one of the following criteria:

    1. Achieved postmenopausal status, defined as: cessation of regular menses for at least 12 consecutive months with no alternative pathological or physiological cause; and have a serum FSH level within the laboratory's reference range for postmenopausal females;
    2. Have undergone a documented hysterectomy and/or bilateral oophorectomy;
    3. Have medically confirmed ovarian failure. All other female subjects (including females with tubal ligations and females that do NOT have a documented hysterectomy, bilateral oophorectomy and/or ovarian failure) will be considered to be of childbearing potential.
  • Body mass index (BMI) of 17.5 to 30.5 kg/m2, inclusive, and a total body weight >50 kg (110 lb).
  • Evidence of a personally signed and dated informed consent document indicating that the subject has been informed of all aspects of the study.
  • Subjects willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.

Exclusion Criteria:

  • Significant ECG abnormality at screening as determined by the investigator.
  • History or risk factors of QT prolongation or torsades de pointes, congenital deafness and family history of sudden death.
  • 12-lead ECG demonstrating QTcF >450 msec or a QRS interval >110 msec at Screening.
  • Use of medications or dietary supplements capable of inducing or inhibiting hepatic enzyme metabolism or transport (e.g., barbiturates, rifampin, carbamazepine, phenytoin, primidone, or St. John's Wort) within 28 days of the first dose of study medication.
  • Consumption of grapefruit or grapefruit containing products within 7 days prior to the first dose of study medication.
  • Known history of hypersensitivity, allergy, severe adverse drug reaction or intolerance to quinolone antibiotics.
  • Known hypersensitivity to benzonatate or other ester-type local anesthetics (ie, tetracaine, procaine).
  • Subjects with a presence or history of dysphagia or difficulty swallowing pills.
  • Subjects taking any concomitant anticonvulsant medications or with a history of seizure disorder.
  • Subjects with a positive response to the question of actual attempt in the suicidal behavior section of the C-SSRS (Columbia-Suicide Severity Rating Scale). Subjects with active suicidal ideation with intent to act within 6 months of screening as determined by a positive response to questions 4 or 5 in the suicidal ideation section of the C-SSRS.
  • Screening laboratory values considered clinically significant by the investigator.
  • Screening supine blood pressure ≥140 mm Hg (systolic) or ≥90 mm Hg (diastolic), following at least 5 minutes of rest.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02207699


Locations
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United States, Kansas
Pfizer Investigational Site
Overland Park, Kansas, United States, 66212
Sponsors and Collaborators
Pfizer
Investigators
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Study Director: Pfizer CT.gov Call Center Pfizer
Additional Information:
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Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT02207699    
Other Study ID Numbers: B3551003
BT-10-02
First Posted: August 4, 2014    Key Record Dates
Last Update Posted: August 4, 2014
Last Verified: July 2014
Additional relevant MeSH terms:
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Moxifloxacin
Benzonatate
Anti-Bacterial Agents
Anti-Infective Agents
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Antitussive Agents
Respiratory System Agents