Provoked Craving Assessment

• ClinicalTrials.gov Identifier: NCT01506908
• Recruitment Status: Completed
• First Posted: January 10, 2012
• Results First Posted: January 30, 2014
• Last Update Posted: August 28, 2019
• Sponsor: GlaxoSmithKline
• Information provided by (Responsible Party): GlaxoSmithKline

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Conditions: Smoking Dependence; Smoking
• Interventions: Drug: oral nicotine; Drug: Placebo
• Enrollment: 323

Participant Flow

Recruitment Details	Participants were recruited at the clinical site.
Pre-assignment Details	Of 423 screened participants, 323 were randomized while 94 did not meet the study criterion and remaining 6 discontinued due to other reasons. All randomized participants had a history of smoking more than 20 cigarettes per day.

Arm/Group Title	Nicotine Lozenge 4 Milligrams (mg)	Matched Placebo
Arm/Group Description	Participants received a single dose of 4 mg nicotine polacrilex mint lozenge, through oral route.	Participants received a single dose of matched placebo mint lozenge, through oral route.
Period Title: Overall Study
Started	162	161
Completed	161	161
Not Completed	1	0
Reason Not Completed
Adverse Event	1	0

Baseline Characteristics

Arm/Group Title		Nicotine Lozenge 4 mg	Matched Placebo	Total
Arm/Group Description		Participants received a single dose of 4 mg nicotine polacrilex mint lozenge, through oral route.	Participants received a single dose of matched placebo mint lozenge, through oral route.	Total of all reporting groups
Overall Number of Baseline Participants		162	161	323
Baseline Analysis Population Description		[Not Specified]
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	162 participants	161 participants	323 participants
		43.69 (12.13)	44.45 (11.64)	44.07 (11.88)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	162 participants	161 participants	323 participants
	Female	75 46.3%	74 46.0%	149 46.1%
	Male	87 53.7%	87 54.0%	174 53.9%
Body Mass Index; Mean (Standard Deviation); Unit of measure: Kilograms (kg)/ meter (m)^2
	Number Analyzed	162 participants	161 participants	323 participants
		27.79 (3.73)	27.56 (4.05)	27.67 (3.89)

Outcome Measures

1. Primary Outcome

Title	Change From Post-cue Baseline in Nicotine Craving Score at 5 Minutes
Description	Participants completed a nicotine craving assessment consisting of following five items: I have a desire for a cigarette right now, if it were possible I would smoke right now, All I want right now is a cigarette, I have an urge for a cigarette, I crave a cigarette right now. All participants indicated their craving intensity on a pre-drawn 100 mm scale ranging from 0 (disagree) to 100 (agree). At the end of the craving assessment period, mean VAS score was measured.
Time Frame	Post-cue baseline,5 minutes

Outcome Measure Data

Analysis Population Description

Intention to Treat (ITT) population: All randomized participants who had at least one cravings assessment measurement post dose. The imputation of missing craving score was based on last observation carried forward (LOCF) technique.

Arm/Group Title	Nicotine Lozenge 4 mg	Matched Placebo
Arm/Group Description:	Participants received a single dose of 4 mg nicotine polacrilex mint lozenge, through oral route.	Participants received a single dose of matched placebo mint lozenge, through oral route.
Overall Number of Participants Analyzed	162	161
Least Squares Mean (95% Confidence Interval); Unit of Measure: Score on a scale
	-41.8; (-45.8 to -37.7)	-25.9; (-30.0 to -21.8)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Nicotine Lozenge 4 mg, Matched Placebo
	Comments	Null hypothesis considered the population’s change from post-cue baseline in craving score mean to be equal in both treatment groups at 5 minutes
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Least squares means difference
	Estimated Value	-15.9
	Confidence Interval	(2-Sided) 95%; -21.6 to -10.2
	Estimation Comments	Treatment comparisons were made between 4 mg nicotine lozenge and placebo lozenge at 5% significance level.

2. Secondary Outcome

Title	Change From Post-cue Baseline in Nicotine Craving Score at 1 Minute
Description	Participants completed a nicotine craving assessment consisting of following five items: I have a desire for a cigarette right now, if it were possible I would smoke right now, All I want right now is a cigarette, I have an urge for a cigarette, I crave a cigarette right now. All participants indicated their craving intensity on a pre-drawn 100 mm scale ranging from 0 (disagree) to 100 (agree). At the end of the craving assessment period, mean VAS score was measured.
Time Frame	Post-cue baseline, 1 minute post treatment administration

Outcome Measure Data

Analysis Population Description

ITT population: All randomized participants who had at least one cravings assessment measurement post dose. The imputation of missing craving score was based on LOCF technique.

Arm/Group Title	Nicotine Lozenge 4 mg	Matched Placebo
Arm/Group Description:	Participants received a single dose of 4 mg nicotine polacrilex mint lozenge, through oral route.	Participants received a single dose of matched placebo mint lozenge, through oral route.
Overall Number of Participants Analyzed	162	161
Least Squares Mean (95% Confidence Interval); Unit of Measure: Score on a scale
	-17.2; (-20.1 to -14.2)	-12.9; (-15.9 to -10.0)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Nicotine Lozenge 4 mg, Matched Placebo
	Comments	Null hypothesis considered the population’s change from post-cue baseline in craving score mean to be equal in both treatment groups at 1 minute.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0511
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Least squares means difference
	Estimated Value	-4.2
	Confidence Interval	(2-Sided) 95%; -8.4 to 0.0
	Estimation Comments	Treatment comparisons were made between 4 mg nicotine lozenge and placebo lozenge at 5% significance level.

3. Secondary Outcome

Title	Change From Post-cue Baseline in Nicotine Craving Score at 3 Minutes
Description	Participants completed a nicotine craving assessment consisting of following five items: I have a desire for a cigarette right now, if it were possible I would smoke right now, All I want right now is a cigarette, I have an urge for a cigarette, I crave a cigarette right now. All participants indicated their craving intensity on a pre-drawn 100 mm scale ranging from 0 (disagree) to 100 (agree). At the end of the craving assessment period, mean VAS score was measured.
Time Frame	Post-cue Baseline, 3 minutes post treatment administration

Outcome Measure Data

Analysis Population Description

ITT population: All randomized participants who had at least one cravings assessment measurement post dose. The imputation of missing craving score was based on LOCF technique.

Arm/Group Title	Nicotine Lozenge 4 mg	Matched Placebo
Arm/Group Description:	Participants received a single dose of 4 mg nicotine polacrilex mint lozenge, through oral route.	Participants received a single dose of matched placebo mint lozenge, through oral route.
Overall Number of Participants Analyzed	162	161
Least Squares Mean (95% Confidence Interval); Unit of Measure: Score on a scale
	-31.1; (-34.8 to -27.5)	-19.6; (-23.2 to -15.9)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Nicotine Lozenge 4 mg, Matched Placebo
	Comments	Null hypothesis considered the population’s change from post-cue baseline in craving score mean to be equal in both treatment groups at 3 minutes.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Least squares means difference
	Estimated Value	-11.6
	Confidence Interval	(2-Sided) 95%; -16.7 to -6.4
	Estimation Comments	Treatment comparisons were made between 4 mg nicotine lozenge and placebo lozenge at 5% significance level.

4. Secondary Outcome

Title	Change From Post-cue Baseline in Nicotine Craving Score at 7 Minutes
Description	Participants completed a nicotine craving assessment consisting of following five items: I have a desire for a cigarette right now, if it were possible I would smoke right now, All I want right now is a cigarette, I have an urge for a cigarette, I crave a cigarette right now. All participants indicated their craving intensity on a pre-drawn 100 mm scale ranging from 0 (disagree) to 100 (agree). At the end of the craving assessment period, mean VAS score was measured.
Time Frame	Post-Cue Baseline, 7 minutes post treatment administration

Outcome Measure Data

Analysis Population Description

ITT population: All randomized participants who had at least one cravings assessment measurement post dose. The imputation of missing craving score was based on LOCF technique.

Arm/Group Title	Nicotine Lozenge 4 mg	Matched Placebo
Arm/Group Description:	Participants received a single dose of 4 mg nicotine polacrilex mint lozenge, through oral route.	Participants received a single dose of matched placebo mint lozenge, through oral route.
Overall Number of Participants Analyzed	162	161
Least Squares Mean (95% Confidence Interval); Unit of Measure: Score on a scale
	-48.2; (-52.5 to -43.9)	-30.5; (-34.8 to -26.2)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Nicotine Lozenge 4 mg, Matched Placebo
	Comments	Null hypothesis considered the population’s change from post-cue baseline in craving score mean to be equal in both treatment groups at 7 minutes.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Least squares means difference
	Estimated Value	-17.8
	Confidence Interval	(2-Sided) 95%; -23.8 to -11.7
	Estimation Comments	Treatment comparisons were made between 4 mg nicotine lozenge and placebo lozenge at 5% significance level.

5. Secondary Outcome

Title	Change From Post-cue Baseline in Nicotine Craving Score at 10 Minutes
Description	Participants completed a nicotine craving assessment consisting of following five items: I have a desire for a cigarette right now, if it were possible I would smoke right now, All I want right now is a cigarette, I have an urge for a cigarette, I crave a cigarette right now. All participants indicated their craving intensity on a pre-drawn 100 mm scale ranging from 0 (disagree) to 100 (agree). At the end of the craving assessment period, mean VAS score was measured.
Time Frame	Post-Cue Baseline, 10 minutes post treatment administration

Outcome Measure Data

Analysis Population Description

ITT population: All randomized participants who had at least one cravings assessment measurement post dose. The imputation of missing craving score was based on LOCF technique

Arm/Group Title	Nicotine Lozenge 4 mg	Matched Placebo
Arm/Group Description:	Participants received a single dose of 4 mg nicotine polacrilex mint lozenge, through oral route.	Participants received a single dose of matched placebo mint lozenge, through oral route.
Overall Number of Participants Analyzed	162	161
Least Squares Mean (95% Confidence Interval); Unit of Measure: Score on a scale
	-50.8; (-55.3 to -46.2)	-32.9; (-37.5 to -28.3)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Nicotine Lozenge 4 mg, Matched Placebo
	Comments	Null hypothesis considered the population’s change from post-cue baseline in craving score mean to be equal in both treatment groups at 10 minutes.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Least square mean difference
	Estimated Value	-17.9
	Confidence Interval	(2-Sided) 95%; -24.4 to -11.4
	Estimation Comments	Treatment comparisons were made between 4 mg nicotine lozenge and placebo lozenge at 5% significance level.

6. Secondary Outcome

Title	Number of Participants With Adverse Events (AEs), Treatment Related AEs, and Serious AEs (SAEs)
Description	AE was defined as any new untoward medical occurrence or worsening of a pre-existing medical condition which does not necessarily have a causal relationship with study treatment/s. Treatment related AE was defined as any AE considered to be possibly, probably or highly probably related to study medication. SAE was defined as any untoward medical occurrence that at any dose results in death; is life threatening; requires hospitalization or prolongation of existing hospitalization results in disability/ incapacity; is a congenital anomaly/ birth defect.
Time Frame	Baseline to Day 5 post treatment administration

Outcome Measure Data

Analysis Population Description

Safety population: All randomized participants who received the study treatments were considered evaluable for safety.

Arm/Group Title	Matched Placebo	Nicotine Lozenge 4 mg
Arm/Group Description:	Participants received a single dose of matched placebo mint lozenge, through oral route.	Participants received a single dose of 4 mg nicotine polacrilex mint lozenge, through oral route.
Overall Number of Participants Analyzed	161	162
Measure Type: Number; Unit of Measure: Participants
AEs	12	54
Treatment Related AEs	11	54
SAEs	0	0

Adverse Events

Time Frame	All adverse events encountered or spontaneously reported following administration of any investigational product (including washout product), or for up to 5 days after the last administration of investigational product were recorded.
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	Nicotine Lozenge 4 mg		Placebo Lozenge
Arm/Group Description	Participants received a single dose of 4 mg nicotine polacrilex mint lozenge, through oral route.		Participants received a single dose of matched placebo mint lozenge, through oral route.
All-Cause Mortality
	Nicotine Lozenge 4 mg		Placebo Lozenge
	Affected / at Risk (%)		Affected / at Risk (%)
Total	--/--		--/--
Serious Adverse Events
	Nicotine Lozenge 4 mg		Placebo Lozenge
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/162 (0.00%)		0/161 (0.00%)
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	1%
	Nicotine Lozenge 4 mg		Placebo Lozenge
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	54/162 (33.33%)		12/161 (7.45%)
Ear and labyrinth disorders
Ear Pain † 1	0/162 (0.00%)	0	1/161 (0.62%)	1
Gastrointestinal disorders
Nausea † 1	24/162 (14.81%)	24	1/161 (0.62%)	1
Dyspepsia † 1	7/162 (4.32%)	7	0/161 (0.00%)	0
Abdominal Discomfort † 1	3/162 (1.85%)	3	1/161 (0.62%)	1
Stomatitis † 1	2/162 (1.23%)	2	1/161 (0.62%)	1
Glossodynia † 1	0/162 (0.00%)	0	2/161 (1.24%)	2
Flatulence † 1	1/162 (0.62%)	1	0/161 (0.00%)	0
Oral Discomfort † 1	1/162 (0.62%)	1	0/161 (0.00%)	0
Investigations
Heart Rate Increased † 1	1/162 (0.62%)	1	1/161 (0.62%)	1
Nervous system disorders
Dizziness † 1	4/162 (2.47%)	4	1/161 (0.62%)	1
Headache † 1	1/162 (0.62%)	1	1/161 (0.62%)	1
Psychiatric disorders
Anxiety † 1	1/162 (0.62%)	1	1/161 (0.62%)	1
Respiratory, thoracic and mediastinal disorders
Hiccups † 1	13/162 (8.02%)	13	1/161 (0.62%)	1
Throat Irritation † 1	5/162 (3.09%)	5	1/161 (0.62%)	1
Nasal Congestion † 1	0/162 (0.00%)	0	1/161 (0.62%)	1
Oropharyngeal Pain † 1	0/162 (0.00%)	0	1/161 (0.62%)	1
† Indicates events were collected by systematic assessment; 1 Term from vocabulary, MedDRA 14.1

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

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

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.

Results Point of Contact

• Name/Title: GSK Response Center
• Organization: GlaxoSmithKline
• Phone: 866-435-7343

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Nides M, Shanga GM, Bishop A, Becker WD. Nicotine Lozenges in the Relief of Behaviorally Provoked Craving. Am J Health Behav. 2018 May 1;42(3):69-80. doi: 10.5993/AJHB.42.3.7.

• Responsible Party: GlaxoSmithKline
• ClinicalTrials.gov Identifier: NCT01506908
• Other Study ID Numbers: S7121359
• First Submitted: December 15, 2011
• First Posted: January 10, 2012
• Results First Submitted: December 12, 2013
• Results First Posted: January 30, 2014
• Last Update Posted: August 28, 2019