Figures
- Figure 1–
Flow diagram of the progress of subjects through the phases of the study.
- Figure 2–
Proportion of subjects with carbon monoxide-verified 7-day point prevalence of abstinence. Includes all subjects (nicotine mouth spray (NMS): n=318; placebo: n=161). *: p<0.05 between the abstinence rates in the NMS group compared with the placebo group.
- Figure 3–
Median of the individual mean daily number of spray doses by study week (weeks 1 to 12) in subjects in the nicotine mouth spray (NMS) group. Sprays/all: all NMS subjects reporting data for at least 50% of the days in that specific period; Sprays/abst: all NMS subjects with verified 7-day point prevalence abstinence reporting data for at least 50% of the days in that specific period.
Tables
- Table 1– Inclusion and exclusion criteria
Inclusion criteria Exclusion criteria Males and females, 18 yrs or older
Daily cigarette smoker for the last 3 yrs or more (no lower limit in number of daily cigarettes)
Expired carbon monoxide level of at least 10 ppm after at least 15 smoke-free min
Motivated and willing to completely stop smoking from the day after the baseline visit and to stay smoke-free
Willing to use study drug for at least 12 weeks
Female participants of child-bearing potential to use a medically acceptable method of birth control
Evidence of a personally signed and dated informed consent document
Willing and able to comply with all study procedures and attend 11 scheduled visits during the 52-week study
Willing and able to use an eDiary, according to the instructions provided, and willing to return the eDiary at the 12-week visitCurrent use of tobacco-containing products, other than cigarettes, or smoking other substances
Use of other NRT, or bupropion or varenicline, or any other treatment for tobacco dependence (e.g. acupuncture)
Unstable angina pectoris or myocardial infarction or stroke during the previous 3 months
Pregnancy, lactation or intended pregnancy
Suspected alcohol or drug abuse
Another member of the same household who is already a subject in the current trial
Participation in any other clinical trial within the previous 3 months, or during the current trial
Any acute or chronic medical or psychiatric condition or previously diagnosed renal or hepatic disease that may increase the risk associated with study participation
Presence of an oral lesion (suspected malignant lesion and/or erosive lesion) that required further investigation, such as biopsyThe text for inclusion and exclusion criteria is appropriately abbreviated. NRT: nicotine replacement therapy.
- Table 2– Treatment-related adverse events: overview and numbers of subjects reporting (by preferred term)
Nicotine mouth spray Placebo Subjects n 318 161 Subjects with at least one adverse event# 278 (87.4) 115 (71.4) Subjects discontinued because of an adverse event 25 (7.9) 11 (6.8) Adverse events (preferred term) reported by ≥10% of subjects in either treatment group Hiccups 182 (57.2) 12 (7.5) Throat irritation 126 (39.6) 45 (28.0) Headache 103 (32.4) 58 (36.0) Nausea 101 (31.8) 39 (24.2) Dyspepsia 93 (29.2) 24 (14.9) Stomatitis 75 (23.6) 27 (16.8) Salivary hypersecretion 68 (21.4) 19 (11.8) Dizziness 61 (19.2) 39 (24.2) Constipation 60 (18.9) 28 (17.4) Dry mouth 44 (13.8) 24 (14.9) Dysgeusia 38 (11.9) 20 (12.4) Burning sensation in mouth 38 (11.9) 13 (8.1) Data are presented as n (%), unless otherwise stated. #: adverse events reported by number of subjects in either treatment group who reported a treatment-related adverse event at least once. “Treatment related” was captured in the case report forms as the answer “Yes/Unknown” to the question “Is there a reasonable possibility the adverse event is related to study treatment?” All the preferred terms in the table above were included as a "health problem" prompt in the eDiary. The “health problem” prompt consisted of a checklist of 14 predefined adverse events (the 12 listed above, plus common cold and vomiting) and an “Other” option. The preferred terms dyspepsia, stomatitis, salivary hypersecretion, dysgeusia, and burning sensation in the mouth were elicited using the following adverse event prompts in the eDiary: heartburn, mouth irritation, excessive salivation, altered taste, and burning lips, respectively.
- Table 3– Baseline demographic characteristics and smoking history
Nicotine mouth spray Placebo Subjects n 318 161 Age yrs 47.0±10.9 46.2±11.3 Sex female 137 (43.1) 73 (45.3) Smoking history –Cigarettes per day 22.7±8.8 22.7±8.7 –Expired CO level ppm 26.4±10.1 26.6±11.3 –Saliva cotinine ng·mL−1 356±154 (n=316) 349±151 (n=159) –Age started smoking yrs 16.6±3.6 (n=317) 16.5±3.6 (n=161) –Never tried to quit before 37 (11.6) 26 (16.1) –0–3 months since last quit attempt 63 (19.8) 28 (17.4) –Previously used stop-smoking medication(s) 171 (53.8) 84 (52.8) (n=159) –Previously used NRT 150 (47.2) 79 (49.1) FTND score 5.3±2.3 5.4±2.2 Time to first cigarette –Within 5 min of waking 94 (29.6) 49 (30.4) –6–30 min after waking 139 (43.7) 76 (47.2) –31–60 min after waking 49 (15.4) 20 (12.4) –>60 min after waking 36 (11.3) 16 (9.9) Blood pressure mmHg 133±18/85±12 (n=313) 132±18/84±11 (n=158) Body mass index kg·m−2 26.3±5.3 (n=313) 26.0±5.1 (n=160) Data are presented as mean±sd or n (%), unless otherwise stated. CO: carbon monoxide; NRT: nicotine replacement therapy; FTND: Fagerström Test of Nicotine Dependence.
- Table 4– Carbon monoxide-verified continuous abstinence rates from week 2 to weeks 4, 6, 8, 12, 16, 20, 24 and 52
Time point Nicotine mouth spray# Placebo¶ p-value+ Risk ratio (95% CI)§ Odds ratio (95% CI)§ Week 4 101 (31.8) 35 (21.7) 0.022 1.46 (1.05–2.04) 1.68 (1.08–2.61) Week 6 83 (26.1) 26 (16.1) 0.014 1.62 (1.09–2.41) 1.83 (1.13–2.99) Week 8 78 (24.5) 23 (14.3) 0.009 1.72 (1.12–2.63) 1.95 (1.17–3.25) Week12 64 (20.1) 21 (13.0) 0.055 1.54 (0.98–2.43) 1.68 (0.98–2.87) Week 16 57 (17.9) 15 (9.3) 0.013 1.92 (1.13–3.29) 2.13 (1.16–3.89) Week 20 53 (16.7) 11 (6.8) 0.003 2.44 (1.31–4.54) 2.73 (1.38–5.38) Week 24 50 (15.7) 11 (6.8) 0.006 2.30 (1.23–4.30) 2.54 (1.29–5.04) Week 52 44 (13.8) 9 (5.6) 0.007 2.48 (1.24–4.94) 2.71 (1.29–5.71) Values are presented as n (%), unless otherwise stated. #: n=318; ¶: n=161; +: p-values were calculated using the Chi-squared test; §: estimated risk ratios/odds ratios and corresponding 95% confidence intervals were calculated using Mantel–Haenszel statistics.
