- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04800211
Biomarkers of Exposure and Biomarkers of Potential Harm in Adult Smokers Who Completely Switch to E-vapor Products
An Open-Label, Parallel-Group, Controlled Study to Evaluate Changes in Biomarkers of Cigarette Smoke Exposure and Biomarkers of Potential Harm in Adult Smokers Who Completely Switch to Using e-Vapor Products for 12 Weeks With Follow-up at 24 Weeks
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Actual)
Phase
- Not Applicable
Contacts and Locations
Study Locations
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California
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Burbank, California, United States, 91505
- LA Clinical Trials
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Kansas
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Wichita, Kansas, United States, 67207
- Heartland Research Associates, LLC
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Kentucky
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Lexington, Kentucky, United States, 40509
- Central Kentucky Research Associates
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Minnesota
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Minneapolis, Minnesota, United States, 55404
- Davita Clinical Research
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Missouri
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Springfield, Missouri, United States, 65802
- QPS Bio-Kinetic
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Nebraska
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Lincoln, Nebraska, United States, 68502
- Celerion
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Nevada
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Las Vegas, Nevada, United States, 89119
- Clinical Research Consortium
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North Carolina
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High Point, North Carolina, United States, 27265
- High Point Clinical Trials Center
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Raleigh, North Carolina, United States, 27617
- Rose Research Center, LLC
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Tennessee
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Knoxville, Tennessee, United States, 37920
- New Orleans Center for Clinical Research
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
Study 1
Subjects must satisfy the following criteria before being enrolled into the study. Subjects must:
- sign an IRB-approved informed consent form (ICF) for the study;
- be between the ages of 30 and 65 years, inclusive, at the time of Screening, Visit 1;
- have > 500 ng/ml urine cotinine measurement at Screening, Visit 1;
have smoked for ≥ 10 years and smoked an average of ≥ 10 manufactured cigarettes per day during the 12 months prior to Screening, Visit 1;
a) Brief periods [i.e., up to 7 consecutive days] of non smoking during the 12 months prior to Screening, Visit 1 due to illness, trying to quit, or participation in a study where smoking was prohibited are acceptable.
- indicate that he/she is "definitely" or "probably" willing and able to replace their cigarettes for 12 weeks with the assigned test e-Vapor product;
- have daily access to text messaging capable cellular phone for daily product use reporting;
have a negative ethanol breath test and amphetamines, opiates, cannabinoids, and cocaine urine drug screen results at Screening, Visit 1;
a) Subjects with a prescription from a licensed physician will not be exempted from this criterion.
- if female (all females), have a negative serum pregnancy test at Visit 1 and negative urine pregnancy test at Visit 2 through Visit 7, inclusive;
if female, heterosexually active, and of childbearing potential (i.e., not surgically sterile or 2 years naturally postmenopausal), must have used a medically accepted method of contraception (listed below in a) and b)) prior to Screening, Visit 1 and must agree to continue to use such method(s) through the End of Study;
- Surgically sterile includes bilateral tubal ligation, Essure, hysterectomy, or bilateral oophorectomy at least 6 months prior to Screening, Visit 1. Naturally postmenopausal is defined as women having 2 years without menses.
- Acceptable methods of contraception are: hormonal (i.e., oral, transdermal patch, implant, or injection) consistently for at least 3 months prior to Screening, Visit 1; double barrier (i.e., condom with spermicide or diaphragm with spermicide) consistently for at least 4 weeks prior to Screening, Visit 1; and intrauterine device for at least 3 months prior to Screening, Visit 1; or only have a partner who has been vasectomized for at least 6 months prior to Screening, Visit 1.
- Be willing and able to comply with the requirements of the study.
Study 2
Subjects must satisfy the following criteria before being enrolled into the study. Subject must:
- have participated in and completed the 12-week ALCS-RA-16-06-EV study and have Baseline biomarker samples collected;
- demonstrate willingness to participate by signing an IRB-approved ICF for the study;
- have demonstrated consistent daily reporting of product use in the 12-week ALCS-RA-16-06-EV (≥ 80% reporting compliance);
- if randomized to a Test group, have reported an average of no more than 10% of Baseline cigarette smoking per day through Week 11 of the 12-week ALCS-RA-16-06-EV study;
- if randomized to a Test group, have reported use of at least two Test product cartridges per week in the 12-week ALCS-RA-16-06-EV study;
- if randomized to a Test group, have eCO measurements of ≤ 8 ppm at each post-Baseline time point in the 12-week ALCS-RA-16-06-EV study;
- have daily access to text messaging capable cellular phone for daily product use reporting;
- if female (all females), have a negative urine pregnancy test at Week 12 (Visit 1) through Week 24 (Visit 5), inclusive;
if female, heterosexually active, and of childbearing potential (i.e., not surgically sterile or 2 years naturally postmenopausal), must have used a medically accepted method of contraception (listed below in a) and b)) prior to Screening, Visit 1 of the 12-week ALCS-RA-16-06-EV study and must agree to continue to use such method(s) through Week 24 (EOS);
- Surgically sterile includes bilateral tubal ligation, Essure, hysterectomy, or bilateral oophorectomy at least 6 months prior to Screening, Visit 1 of the 12-week ALCS-RA-16-06-EV study. Naturally postmenopausal is defined as women having 2 years without menses.
- Acceptable methods of contraception are: hormonal (i.e., oral, transdermal patch, implant, or injection) consistently for at least 3 months prior to Screening, Visit 1 of the 12-week ALCS-RA-16-06-EV study; double barrier (i.e., condom with spermicide or diaphragm with spermicide) consistently for at least 4 weeks prior to Screening, Visit 1 of the 12-week ALCS-RA-16-06-EV study; and intrauterine device for at least 3 months prior to Screening, Visit 1 of the 12-week ALCS-RA-16-06-EV study; or only have a partner who has been vasectomized for at least 6 months prior to Screening, Visit 1 of the 12-week ALCS-RA-16-06-EV study.
- Be willing and able to comply with the requirements of the study.
Exclusion Criteria:
Study 1
Subjects may be excluded from the study if there is evidence of any of the following criteria. Exceptions may be permitted at the discretion of the Investigator and in consultation with the Sponsor or designee provided there would be no additional risk to the subject. Any exceptions will be documented.
- History or presence of clinically significant gastrointestinal, renal, hepatic, neurologic, hematologic, endocrine, oncologic, urologic, diabetes, existing respiratory diseases, immunologic, psychiatric, or cardiovascular disease, or any other condition that, in the opinion of the Investigator, would jeopardize the safety of the subject or impact the validity of the study results. (Note: chronic medical conditions controlled and on stable medications [over past 3 months] may not necessarily be exclusionary per Investigator discretion);
- Currently taking medication for depression, asthma or diabetes;
- Allergy to menthol;
- Systolic blood pressure > 140 mmHg and / or diastolic blood pressure > 90 mmHg at Screening Visit 1.
- Have clinically significant abnormal findings on the physical examination, vital signs, electrocardiogram (ECG), or medical history that would jeopardize the safety of the subject, in the opinion of the Investigator;
- Positive test for human immunodeficiency virus (HIV), hepatitis B surface antigen (HbsAg), or hepatitis C virus (HCV) at Screening, Visit 1;
- Current evidence or any history of congestive heart failure;
- Any acute illness (e.g., upper respiratory infection, viral infection) requiring treatment within 2 weeks before Visit 3 (Day 1);
- History of drug or alcohol abuse within 24 months of Visit 3 (Day 1) as defined by the Investigator;
- BMI greater than 40.0 kg/m2 or less than 18.0 kg/m2 at Screening, Visit 1;
- Post-bronchodilator FEV1:FVC ratio < 0.7 and FEV1 < 50% of predicted at Screening, Visit 2;
- Post-bronchodilator FEV1:FVC ratio < 0.75 and FEV1 increase ≥ 12% and > 200 mL from pre- to post-bronchodilator at Screening, Visit 2;
- Estimated creatinine clearance (by Cockcroft-Gault equation) < 80 mL/min at Screening, Visit 1;
- Serum alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) > 1.5 times the upper limit of the reference range at Screening, Visit 1;
- Female candidates who are pregnant, lactating, or intend to become pregnant from Screening, Visit 1 through End of Study;
- Use of HDL-C raising medication / supplements (e.g., niacin, gemfibrizole, fenofibrate, etc.) within the past 3 months prior to Screening, Visit 1 or any time during the study;
- Use of nicotine-containing products other than manufactured cigarettes (e.g., roll-your-own cigarettes, e-cigarette or e-Vapor products, Bidis, snuff, nicotine inhaler, pipe, cigar, smokeless tobacco, nicotine patch, nicotine spray, nicotine lozenge, or nicotine gum) within 14 days prior to Screening, Visit 1 through Visit 3 (Day 1) except as required for the purpose of this study;
- Donation of blood or blood products, including plasma, history of significant blood loss in the opinion of the investigator, or receipt of whole blood or a blood product transfusion within 60 days prior to Visit 3 (Day 1);
- Participation in a clinical study of an investigational drug, medical device, biologic, or of a tobacco product, within 30 days before Visit 3 (Day 1);
- Participation in more than two ALCS studies within 12 months before Visit 3 (Day 1);
- Already enrolled or failed screening for the current study at a different study site;
- Subject or a first-degree relative (i.e., parent, spouse, sibling, or child) is a current or former employee of the tobacco industry or a named party or class representative in litigation with any tobacco company.
Study 2
Subjects may be excluded from the study if there is evidence of any of the following. Exceptions may be permitted at the discretion of the Investigator and in consultation with the Sponsor or designee provided there would be no additional risk to the subject. Any exceptions will be documented.
- Have clinically significant abnormal findings on the physical examination, vital signs, or ECG at the EOS visit (Visit 7) of the 12-week ALCS-RA-16-06-EV study that would jeopardize the safety of the subject, in the opinion of the Investigator;
- Female subjects who are pregnant (as determined at the EOS visit [Visit 7] of the 12-week study), lactating, or intend to become pregnant from Visit 1 (Week 12) through Week 24 (EOS);
- Use of any medication for depression, asthma, or diabetes at any time during the study;
- Use of HDL-C raising medication / supplements (e.g., niacin, gemfibrozil, fenofibrate, etc.) at any time during the study;
- Subject or a first-degree relative (i.e., parent, spouse, sibling, or child) is a current or former employee of the tobacco industry or a named party or class representative in litigation with any tobacco company;
- Subject or a first-degree relative (i.e., parent, spouse, sibling, or child) is a current or former employee of Celerion or any of the clinical study sites.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Other
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
No Intervention: Control
Continue smoking under ad libitum use of subjects' own brand of conventional lit-end cigarettes, without use of any other type of tobacco/nicotine containing product, for the entire duration of study participation.
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Experimental: Test 1
Exclusive ad libitum use of test e-Vapor Product NuMark LLC, MarkTen® XL Bold CLASSIC* without use of any other type of tobacco/nicotine containing product, for the entire duration of study participation. *Product no longer sold commercially |
Subjects were instructed to completely replace their cigarettes with the Test Product 1 EVP (Nu Mark LLC, MarkTen® XL Bold CLASSIC)
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Experimental: Test 2
Exclusive ad libitum use of test e-Vapor Product Nu Mark LLC, MarkTen® XL Bold MENTHOL* without use of any other type of tobacco/nicotine containing product, for the entire duration of study participation. *Product no longer sold commercially |
Subjects were instructed to completely replace their cigarettes with the Test Product 2 EVP (Nu Mark LLC, MarkTen® XL Bold MENTHOL)
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Total NNAL
Time Frame: 24 weeks
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Urinary total 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol and its glucuronides (ng/g creatinine)
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24 weeks
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WBC
Time Frame: 24 weeks
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White blood cell count in whole blood (µg/L)
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24 weeks
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COHb
Time Frame: 24 weeks
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Carboxyhemoglobin (percent), blood
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24 weeks
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HDL-C
Time Frame: 24 weeks
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High-density lipoprotein cholesterol in serum (mg/dL)
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24 weeks
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sICAM-1
Time Frame: 24 weeks
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Blood Soluble Intercellular Adhesion Molecule-1 (sICAM-1)
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24 weeks
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11-dehydrothromboxane B2
Time Frame: 24 weeks
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11-dehydrothromboxane B2 in urine with creatinine adjusted (ng/g Cr)
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24 weeks
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8-epi-prostaglandin F2α
Time Frame: 24 weeks
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8-epi-prostaglandin F2α in urine with creatinine adjusted (ng/g Cr)
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24 weeks
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
NNN
Time Frame: 24 weeks
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Creatinine-adjusted n-nitrosonornicotine in urine (ng/g Cr)
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24 weeks
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eCO
Time Frame: 24 weeks
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Exhaled carbon monoxide (ppm)
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24 weeks
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Test product use
Time Frame: 24 weeks
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The number of new cartridges used each day, self-reported by subjects through text message.
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24 weeks
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Puff count
Time Frame: 24 weeks
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The number of puffs taken per cartridge, self-reported by subjects through text message.
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24 weeks
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CPD
Time Frame: 24 weeks
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Number of cigarettes per day smoked, self-reported by subjects through text message.
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24 weeks
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FVC
Time Frame: 24 weeks
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Forced Vital Capacity (L) spirometric measure (Study 2 only)
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24 weeks
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FEV1
Time Frame: 24 weeks
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Forced Expiratory Volume in the first second (L/s) spirometric measure (Study 2 only)
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24 weeks
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Collaborators and Investigators
Sponsor
Investigators
- Study Director: Jeffery Edmiston, PhD, Altria Client Services
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Other Study ID Numbers
- ALCS-RA-16-06/ALCS-RA-17-11-EV
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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