Randomized Trial to Evaluate the Effectiveness of X-22 as a Smoking Cessation Aid

• Sponsor: 22nd Century Limited, LLC (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01400815
• Collaborator: (none)
• Enrollment: 234
• Locations: 3
• Arms: 2
• Actual Duration (Months): 17.1
• Patients Per Site: 78
• Patients Per Site Per Month: 4.6

Study Details

Study Description

Brief Summary

A randomized, active controlled clinical trial in which a total of 216 healthy smokers will be enrolled and followed over approximately 19 weeks.

The trial will evaluate the efficacy and safety of using X-22 as a smoking cessation aid.

Healthy smokers who plan to quit smoking will be screened for eligibility. Subjects will be randomized in a 1:1 ratio to 1 of the 2 treatment arms:

• Group 1: X-22 Cigarettes (very low nicotine)

• Group 2: Active Control Cigarettes The randomization will be stratified by gender. Efficacy will be assessed by analysis of cigarette consumption using self-report diaries and measurement of exhaled carbon monoxide (CO) and cotinine concentrations.

Safety will be assessed by evaluation of adverse events, physical examinations, clinical laboratory tests, and measurement of heart rate, blood pressure, and body weight at each study visit.

Condition or Disease	Intervention/Treatment	Phase
Smoking Cessation	Drug: X-22 Smoking Cessation Product; Drug: Active Control Cigarettes	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 234 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Prospective, Double-blind, Randomized, Active Controlled, Parallel Group, Multicenter Phase II Clinical Trial to Evaluate the Effectiveness of X-22 as a Smoking Cessation Aid
• Actual Study Start Date: Jul 1, 2011
• Actual Primary Completion Date: Dec 1, 2012
• Actual Study Completion Date: Dec 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: X-22 Smoking Cessation Product The X-22 Smoking Cessation Product is a tobacco-based (botanical) medical product consisting of very low nicotine (VLN) cigarettes.	Drug: X-22 Smoking Cessation Product; The X-22 Smoking Cessation Product is a tobacco-based (botanical) medical product consisting of very low nicotine (VLN) cigarettes. Subjects will be allowed to smoke as much as desired throughout the 6-week treatment period.
Active Comparator: Active Control Cigarette The Active Control cigarette is identical to the X-22 cigarette except for the tobacco, which has a nicotine content similar to that of a conventional "light" cigarette.	Drug: Active Control Cigarettes; The Active Control cigarette is identical to the X-22 cigarette except for the tobacco, which has a nicotine content similar to that of a conventional "light" cigarette. Subjects will be allowed to smoke as much as desired throughout the 6-week treatment period.

Outcome Measures

Primary Outcome Measures

1. Efficacy - 4 Weeks of Continuous Abstinence From Smoking Cigarettes [Weeks 7 and 9 = telephone call, Week 8 = visit 6 and Week 10 = visit 7]

   The primary efficacy measurement is the number of subjects with 4 weeks of continuous abstinence from smoking cigarettes (Weeks 7-10), as assessed by subject diary and confirmed by exhaled carbon monoxide (CO), after treatment termination, at Visits 6 and 7. A responder: did not smoke and had less than 10 ppm exhaled CO.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Subjects must meet all of the following inclusion criteria to be eligible for participation in this study.

1. Subjects must be considered by the investigator to be in general good health and between 18 and 65 years of age, inclusive.

2. Subjects must have a history of smoking at least 10 cigarettes per day for at least 1 year, with less than 3 months of abstinence during the past year, and a continuous smoking history for at least 3 months prior to study entry.

3. Subjects must indicate that they plan to quit smoking within the next 3 months.

4. Subjects must have a CO measurement of ≥ 10 ppm at screening and baseline (Visit 1 and Visit 2).

5. Subjects must be willing and able to return for scheduled follow-up examinations for a total of 5 months.

6. Female subjects must have been postmenopausal for the previous 6 months or be surgically sterile, or must have a negative pregnancy test and use one of the following acceptable methods of birth control for the duration of the study and for at least 3 months prior to screening:

• abstinence, meaning a total lack of sexual activity,

• oral contraceptives ("the pill"),

• contraceptive injections,

• intrauterine device,

• double-barrier method (diaphragm or condom plus spermicidal cream),

• contraceptive patch, hormonal implant, hormonal vaginal ring, or

• male partner sterilization at least 3 months prior to screening. 7. Subjects must sign and be given a copy of the written Informed Consent form. 8. Subjects must be able to read, understand and complete the questionnaires independently.

Exclusion Criteria:

• Subjects who meet any of the following exclusion criteria are not to be enrolled in this study.

1. Subjects who have a household member who is already enrolled in this trial.

2. Subjects who have attempted to quit smoking using one or more FDA-approved smoking cessation products (eg, nicotine replacement therapy [NRT] including nicotine gum, nicotine lozenges, nicotine patches, nicotine nasal spray, or nicotine inhaler; Zyban [bupropion]; or Chantix [varenicline]) for longer than 1 week in the past 3 months.

3. Subjects who have been enrolled in another structured smoking cessation program (e.g., behavioral modification, hypnosis, acupuncture, or other alternative therapies) in the last 30 days.

4. Subjects who have been in another smoking cessation trial in the past 6 months.

5. Subjects who regularly use (greater than once per month) tobacco-based products other than cigarettes (eg, chew, snuff, snus, shisha, etc.).

6. Subjects with a history of coronary artery disease, myocardial infarction, stroke, chronic obstructive pulmonary disease, or other significant pulmonary diseases. Controlled hypertensive subjects and mild asthmatics whose disease is controlled only with an as-needed inhaled beta agonist are acceptable.

7. Subjects with a history of cancer within the past 60 months other than basal cell carcinoma.

8. Subjects with a history of thromboembolic disease or taking warfin or any other anticoagulant, or anti-platelet drug such as clopidogrel (Plavix®) or pentoxifylline (Trental®). Low dose aspirin therapy is acceptable.

9. Subjects with screening laboratory abnormalities that are considered by the investigator to be clinically significant.

10. Subjects with a body mass index (BMI) >35.

11. Subjects with poorly controlled diabetes or insulin-dependent diabetes.

12. Subjects with other known serious pathophysiology or topical or systemic disorders of any kind that would confound the results of the study.

13. Subjects with screening ECG abnormalities that are considered by the investigator to be clinically significant.

14. Subjects who have used any illegal drug in the past 3 months.

15. Subjects who have a positive urine drug screening result.

16. Subjects who are pregnant or lactating, or who plan to become pregnant during the course of the study.

17. Subjects participating in any other clinical trial of an investigational drug or device during the time of this clinical investigation or within 30 days prior to Screening visit.

18. Subjects taking anti-depressants, anti-psychotics, clonidine, or any of the classes of drugs listed in the RapidCHECK® 12 Panel in the last 60 days (see Section 12.1.1).

19. Subjects with systolic blood pressure over 140 mmHg and/or diastolic blood pressure over 90 mmHg.

20. Subjects consuming an average of 3 or more drinks of alcohol per day.

21. Subjects consuming greater than an average of 2 packs of cigarettes per day.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Benchmark Research Sacramento	Sacramento	California	United States	95816
2	Benchmark Research New Orleans	Metairie	Louisiana	United States	70006
3	Benchmark Research Austin	Austin	Texas	United States	78705

Sponsors and Collaborators

• 22nd Century Limited, LLC

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: 22nd Century Limited, LLC
• ClinicalTrials.gov Identifier: NCT01400815
• Other Study ID Numbers: X-22-201
• First Posted: Jul 22, 2011
• Last Update Posted: Nov 19, 2021
• Last Verified: Oct 1, 2021

• Keywords provided by 22nd Century Limited, LLC: smoking; smoking cessation; quitting smoking

Study Results

Participant Flow

Arm/Group Title	X-22 Smoking Cessation Product	Active Control Cigarette
Arm/Group Description	The X-22 Smoking Cessation Product is a tobacco-based (botanical) medical product consisting of very low nicotine (VLN) cigarettes. X-22 Smoking Cessation Product: The X-22 Smoking Cessation Product is a tobacco-based (botanical) medical product consisting of very low nicotine (VLN) cigarettes. Subjects will be allowed to smoke as much as desired throughout the 6-week treatment period.	The Active Control cigarette is identical to the X-22 cigarette except for the tobacco, which has a nicotine content similar to that of a conventional "light" cigarette. Active Control Cigarettes: The Active Control cigarette is identical to the X-22 cigarette except for the tobacco, which has a nicotine content similar to that of a conventional "light" cigarette. Subjects will be allowed to smoke as much as desired throughout the 6-week treatment period.
Period Title: Overall Study
STARTED	118	116
COMPLETED	80	95
NOT COMPLETED	38	21

Baseline Characteristics

Arm/Group Title	X-22 Smoking Cessation Product	Active Control Cigarette	Total
Arm/Group Description	The X-22 Smoking Cessation Product is a tobacco-based (botanical) medical product consisting of very low nicotine (VLN) cigarettes. X-22 Smoking Cessation Product: The X-22 Smoking Cessation Product is a tobacco-based (botanical) medical product consisting of very low nicotine (VLN) cigarettes. Subjects will be allowed to smoke as much as desired throughout the 6-week treatment period.	The Active Control cigarette is identical to the X-22 cigarette except for the tobacco, which has a nicotine content similar to that of a conventional "light" cigarette. Active Control Cigarettes: The Active Control cigarette is identical to the X-22 cigarette except for the tobacco, which has a nicotine content similar to that of a conventional "light" cigarette. Subjects will be allowed to smoke as much as desired throughout the 6-week treatment period.	Total of all reporting groups
Overall Participants	118	116	234
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	42.1 (11.0)	41.8 (11.2)	41.9 (11.1)
Sex: Female, Male (Count of Participants)
Female	54 45.8%	52 44.8%	106 45.3%
Male	64 54.2%	64 55.2%	128 54.7%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	2 1.7%	1 0.9%	3 1.3%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	26 22%	33 28.4%	59 25.2%
White	88 74.6%	81 69.8%	169 72.2%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	2 1.7%	1 0.9%	3 1.3%

Outcome Measures

1. Primary Outcome

Title	Efficacy - 4 Weeks of Continuous Abstinence From Smoking Cigarettes
Description	The primary efficacy measurement is the number of subjects with 4 weeks of continuous abstinence from smoking cigarettes (Weeks 7-10), as assessed by subject diary and confirmed by exhaled carbon monoxide (CO), after treatment termination, at Visits 6 and 7. A responder: did not smoke and had less than 10 ppm exhaled CO.
Time Frame	Weeks 7 and 9 = telephone call, Week 8 = visit 6 and Week 10 = visit 7

Outcome Measure Data

Analysis Population Description

intent to treat (ITT) population

Arm/Group Title	X-22 Smoking Cessation Product	Active Control Cigarette
Arm/Group Description	The X-22 Smoking Cessation Product is a tobacco-based (botanical) medical product consisting of very low nicotine (VLN) cigarettes. X-22 Smoking Cessation Product: The X-22 Smoking Cessation Product is a tobacco-based (botanical) medical product consisting of very low nicotine (VLN) cigarettes. Subjects will be allowed to smoke as much as desired throughout the 6-week treatment period.	The Active Control cigarette is identical to the X-22 cigarette except for the tobacco, which has a nicotine content similar to that of a conventional "light" cigarette. Active Control Cigarettes: The Active Control cigarette is identical to the X-22 cigarette except for the tobacco, which has a nicotine content similar to that of a conventional "light" cigarette. Subjects will be allowed to smoke as much as desired throughout the 6-week treatment period.
Measure Participants	118	116
Week 8 - No Cigarettes Smoked per Diary (Weeks 7 and 8)	14 11.9%	14 12.1%
Week 8 - Exhaled CO <= 10ppm	32 27.1%	36 31%
Week 8 responder	14 11.9%	11 9.5%
Week 10 - No Cigarettes Smoked per Diary (Weeks 9 and 10)	16 13.6%	18 15.5%
Week 10 - Exhaled CO <= 10ppm	38 32.2%	30 25.9%
Week 10 responder	16 13.6%	13 11.2%
Overall Responder	13 11%	10 8.6%

Adverse Events

Arm/Group Title	X-22 Smoking Cessation Product		Active Control Cigarette
Arm/Group Description	The X-22 Smoking Cessation Product is a tobacco-based (botanical) medical product consisting of very low nicotine (VLN) cigarettes. X-22 Smoking Cessation Product: The X-22 Smoking Cessation Product is a tobacco-based (botanical) medical product consisting of very low nicotine (VLN) cigarettes. Subjects will be allowed to smoke as much as desired throughout the 6-week treatment period.		The Active Control cigarette is identical to the X-22 cigarette except for the tobacco, which has a nicotine content similar to that of a conventional "light" cigarette. Active Control Cigarettes: The Active Control cigarette is identical to the X-22 cigarette except for the tobacco, which has a nicotine content similar to that of a conventional "light" cigarette. Subjects will be allowed to smoke as much as desired throughout the 6-week treatment period.
All Cause Mortality
	X-22 Smoking Cessation Product		Active Control Cigarette
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/118 (0%)		1/116 (0.9%)
Serious Adverse Events
	X-22 Smoking Cessation Product		Active Control Cigarette
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/118 (4.2%)		1/116 (0.9%)
Gastrointestinal disorders
Abdominal hernia obstructive	1/118 (0.8%)	1	0/116 (0%)	0
Infections and infestations
Sepsis	0/118 (0%)	0	1/116 (0.9%)	1
Injury, poisoning and procedural complications
Head injury	1/118 (0.8%)	1	0/116 (0%)	0
Traumatic coma	1/118 (0.8%)	1	0/116 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Uterine leiomyoma	1/118 (0.8%)	1	0/116 (0%)	0
Psychiatric disorders
Alcoholism	1/118 (0.8%)	1	0/116 (0%)	0
Other (Not Including Serious) Adverse Events
	X-22 Smoking Cessation Product		Active Control Cigarette
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	60/118 (50.8%)		58/116 (50%)
Blood and lymphatic system disorders
Blood disorder	0/118 (0%)	0	1/116 (0.9%)	1
Leukocytosis	1/118 (0.8%)	1	0/116 (0%)	0
Lymphadenopathy	0/118 (0%)	0	1/116 (0.9%)	1
Ear and labyrinth disorders
Ear Pain	0/118 (0%)	0	1/116 (0.9%)	1
Tympanic membrane perforation	0/118 (0%)	0	1/116 (0.9%)	1
Endocrine disorders
Hypothyroidism	1/118 (0.8%)	1	1/116 (0.9%)	1
Eye disorders
Astigmatism	1/118 (0.8%)	1	0/116 (0%)	0
Dark circles under eyes	1/118 (0.8%)	1	0/116 (0%)	0
Myopia	1/118 (0.8%)	1	0/116 (0%)	0
Retinal disorder	0/118 (0%)	0	1/116 (0.9%)	1
Visual impairment	0/118 (0%)	0	1/116 (0.9%)	1
Gastrointestinal disorders
Abdominal discomfort	0/118 (0%)	0	1/116 (0.9%)	1
Abdominal hernia obstructive	1/118 (0.8%)	1	0/116 (0%)	0
Abdominal pain lower	0/118 (0%)	0	1/116 (0.9%)	1
Abdominal pain upper	0/118 (0%)	0	2/116 (1.7%)	2
Constipation	0/118 (0%)	0	4/116 (3.4%)	4
Diarrhoea	1/118 (0.8%)	1	0/116 (0%)	0
Dyspepsia	2/118 (1.7%)	2	0/116 (0%)	0
Food poisoning	2/118 (1.7%)	2	0/116 (0%)	0
Gingival bleeding	0/118 (0%)	0	1/116 (0.9%)	1
Gingivitis	1/118 (0.8%)	1	0/116 (0%)	0
Nausea	2/118 (1.7%)	2	1/116 (0.9%)	1
Oral Pain	1/118 (0.8%)	1	0/116 (0%)	0
Tooth loss	0/118 (0%)	0	1/116 (0.9%)	1
Toothache	0/118 (0%)	0	1/116 (0.9%)	1
Vomiting	2/118 (1.7%)	2	0/116 (0%)	0
General disorders
Chest Pain	1/118 (0.8%)	1	1/116 (0.9%)	1
Irritability	1/118 (0.8%)	1	0/116 (0%)	0
Pyrexia	1/118 (0.8%)	1	0/116 (0%)	0
Immune system disorders
Seasonal allergy	0/118 (0%)	0	1/116 (0.9%)	1
Infections and infestations
Abscess	1/118 (0.8%)	1	0/116 (0%)	0
Bronchitis	1/118 (0.8%)	1	2/116 (1.7%)	2
Cellulitis	1/118 (0.8%)	1	0/116 (0%)	0
Ear infection	0/118 (0%)	0	1/116 (0.9%)	1
Gastroenteritis viral	0/118 (0%)	0	1/116 (0.9%)	1
Groin abscess	0/118 (0%)	0	1/116 (0.9%)	1
Influenza	1/118 (0.8%)	1	0/116 (0%)	0
Kidney infection	0/118 (0%)	0	1/116 (0.9%)	1
Laryngitis	2/118 (1.7%)	2	0/116 (0%)	0
Localised infection	1/118 (0.8%)	1	0/116 (0%)	0
Lower respiratory tract infection	0/118 (0%)	0	2/116 (1.7%)	2
Nasopharyngitis	20/118 (16.9%)	20	17/116 (14.7%)	17
Oral herpes	0/118 (0%)	0	1/116 (0.9%)	1
Osteomyelitis	0/118 (0%)	0	1/116 (0.9%)	1
Pharyngitis	0/118 (0%)	0	1/116 (0.9%)	1
Pneumonia	0/118 (0%)	0	1/116 (0.9%)	1
Post procedural infection	1/118 (0.8%)	1	0/116 (0%)	0
Sepsis	0/118 (0%)	0	1/116 (0.9%)	1
Sinusitis	2/118 (1.7%)	2	3/116 (2.6%)	3
Tooth infection	3/118 (2.5%)	3	0/116 (0%)	0
Upper respiratory tract infection	0/118 (0%)	0	1/116 (0.9%)	1
Urinary tract infection	0/118 (0%)	0	1/116 (0.9%)	1
Varicella	1/118 (0.8%)	1	0/116 (0%)	0
Injury, poisoning and procedural complications
Ear Injury	1/118 (0.8%)	1	0/116 (0%)	0
Excoriation	1/118 (0.8%)	1	0/116 (0%)	0
Eye injury	1/118 (0.8%)	1	0/116 (0%)	0
Foot fracture	0/118 (0%)	0	1/116 (0.9%)	1
Head injury	2/118 (1.7%)	2	0/116 (0%)	0
Joint sprain	2/118 (1.7%)	2	2/116 (1.7%)	2
Laceration	3/118 (2.5%)	3	0/116 (0%)	0
Limb Injury	0/118 (0%)	0	1/116 (0.9%)	1
Muscle strain	0/118 (0%)	0	1/116 (0.9%)	1
Procedural pain	1/118 (0.8%)	1	0/116 (0%)	0
Traumatic coma	1/118 (0.8%)	1	0/116 (0%)	0
Investigations
Blood carbon monoxide increased	1/118 (0.8%)	1	0/116 (0%)	0
Blood creatinine increased	0/118 (0%)	0	1/116 (0.9%)	1
Blood lactate dehydrogenase increased	0/118 (0%)	0	1/116 (0.9%)	1
Blood potassium increased	1/118 (0.8%)	1	1/116 (0.9%)	1
Blood pressure increased	1/118 (0.8%)	1	2/116 (1.7%)	2
Gamma-glutamyltransferase increased	1/118 (0.8%)	1	1/116 (0.9%)	1
Haematocrit decreased	0/118 (0%)	0	1/116 (0.9%)	1
Haemoglobin decreased	0/118 (0%)	0	1/116 (0.9%)	1
Red blood cell count decreased	0/118 (0%)	0	1/116 (0.9%)	1
Metabolism and nutrition disorders
Glucose tolerance impaired	1/118 (0.8%)	1	0/116 (0%)	0
Hypercholesterolaemia	1/118 (0.8%)	1	0/116 (0%)	0
Increased appetite	1/118 (0.8%)	1	0/116 (0%)	0
Vitamin D deficiency	1/118 (0.8%)	1	0/116 (0%)	0
Musculoskeletal and connective tissue disorders
Arthralgia	0/118 (0%)	0	1/116 (0.9%)	1
Back pain	1/118 (0.8%)	1	0/116 (0%)	0
Myalgia	1/118 (0.8%)	1	0/116 (0%)	0
Pain in extremity	2/118 (1.7%)	2	2/116 (1.7%)	2
Rheumatoid arthritis	0/118 (0%)	0	1/116 (0.9%)	1
Tendonitis	1/118 (0.8%)	1	0/116 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Uterine leiomyoma	1/118 (0.8%)	1	0/116 (0%)	0
Nervous system disorders
Dizziness	3/118 (2.5%)	3	1/116 (0.9%)	1
Dysgeusia	1/118 (0.8%)	1	0/116 (0%)	0
Headache	5/118 (4.2%)	5	8/116 (6.9%)	8
Nerve compression	0/118 (0%)	0	1/116 (0.9%)	1
Sinus headache	1/118 (0.8%)	1	1/116 (0.9%)	1
VIIth nerve paralysis	1/118 (0.8%)	1	0/116 (0%)	0
Psychiatric disorders
Alcoholism	1/118 (0.8%)	1	0/116 (0%)	0
Anxiety	2/118 (1.7%)	2	0/116 (0%)	0
Attention deficit/hyperactivity disorder	0/118 (0%)	0	2/116 (1.7%)	2
Depression	0/118 (0%)	0	1/116 (0.9%)	1
Insomnia	0/118 (0%)	0	2/116 (1.7%)	2
Reproductive system and breast disorders
Menorrhagia	0/118 (0%)	0	1/116 (0.9%)	1
Respiratory, thoracic and mediastinal disorders
Cough	7/118 (5.9%)	7	7/116 (6%)	7
Dysphonia	0/118 (0%)	0	1/116 (0.9%)	1
Increased upper airway secretion	1/118 (0.8%)	1	0/116 (0%)	0
Nasal congestion	5/118 (4.2%)	5	3/116 (2.6%)	3
Oropharyngeal pain	0/118 (0%)	0	5/116 (4.3%)	5
Respiratory tract congestion	2/118 (1.7%)	2	2/116 (1.7%)	2
Rhinorrhoea	0/118 (0%)	0	2/116 (1.7%)	2
Throat irritation	0/118 (0%)	0	1/116 (0.9%)	1
Upper-airway cough syndrome	0/118 (0%)	0	3/116 (2.6%)	3
Skin and subcutaneous tissue disorders
Dermatitis allergic	0/118 (0%)	0	1/116 (0.9%)	1
Pruritus	0/118 (0%)	0	1/116 (0.9%)	1
Vascular disorders
Hypertension	2/118 (1.7%)	2	2/116 (1.7%)	2

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The PI's have a general obligation of confidentiality, which extends to the study results and data procured under the study. There are exceptions to this obligation of confidentiality, which include the disclosure of study information and results in connection with publication and is necessary for the medical care of a study subject.