Smoking Cessation
Conditions
Brief summary
In smokers who are motivated to stop smoking, treatment with lorcaserin compared with placebo will provide greater abstinence as measured by the last 4 weeks of treatment (Weeks 9-12). The target quit date was Day 15.
Interventions
DRUGAPD356-lorcaserin hydrochloride
DRUGPlacebo
Sponsors
Arena Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
1. Males or females aged 18-65 years, inclusive 2. ≥10 cigarettes per day with no period of abstinence longer than 3 months in the past year and who are motivated to quit smoking 3. Able to give signed informed consent 4. Eligible female patients will be: 1. non-pregnant 2. non-lactating 3. agree to use an acceptable method of effective contraception during the study 5. Eligible male patients agree to use contraception when sexually active with a female partner who is not using an acceptable method of birth control 6. Body weight of ≥50 kg (110 pounds), inclusive 7. Considered to be in stable health in the opinion of the investigator
Exclusion criteria
Patients who meet any of the following criteria will be excluded from the study. 1. Prior or current use of lorcaserin HCl 2. Prior participation in any study of a nicotine vaccination 3. Use of other therapies for smoking cessation is not allowed within 3 months of screening through study exit 4. Use of tobacco products other than cigarettes 5. Prior use of fenfluramine or dexfenfluramine 6. Serious or unstable medical condition or clinically significant new illness within the 6 months prior to screening 7. Previous participation in any clinical study within 6 weeks prior to the screening visit 8. History of severe allergies, severe drug or excipient allergy or hypersensitivity 9. History of significant cardiovascular condition 10. History of other significant medical conditions 11. Significant risk of suicide 12. Anticipated use of any agents that are associated with valvulopathy and/or pulmonary hypertension 13. Positive test result for human immunodeficiency virus (HIV), hepatitis B, or hepatitis C 14. Recent history of alcohol or drug/solvent abuse 15. Concurrent participation in the study by more than one member of the same household 16. Not suitable to participate in the study in the opinion of the investigator
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Abstinence for the Last 4 Weeks of Treatment From Weeks 9-12 | Week 9 - Week 12 | Primary efficacy was assessed as the CO (carbon monoxide)-confirmed continuous abstinence rate for the last 4 weeks of treatment (Month 3: Weeks 9 through 12), defined as no reported smoking (not even a puff) or other nicotine use, verified by end expiratory CO levels \<= 10 ppm. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Abstinence During Weeks 3-12 | Week 3 to Week 12 | The CO (carbon monoxide)-confirmed continuous abstinence rate for Weeks 3 through 12, defined as no reported smoking (not even a puff) or other nicotine use, verified by end expiratory CO levels \<= 10 ppm |
| The 7 Day Point Prevalence or Weekly Abstinence at Week 8 | Week 8 | The CO (carbon monoxide)-confirmed continuous abstinence rate at for the 7-day period preceding the Week 8 visit, defined as no reported smoking (not even a puff) or other nicotine use, verified by end expiratory CO levels \<= 10 ppm |
| The 7 Day Point Prevalence or Weekly Abstinence at Week 12 | Week 12 | The CO (carbon monoxide)-confirmed continuous abstinence rate at for the 7-day period preceding the Week 12 visit, defined as no reported smoking (not even a puff) or other nicotine use, verified by end expiratory CO levels \<= 10 ppm |
| Body Weight | Baseline to Week 12 | Change in body weight from Week 1 (baseline) to Week 12 |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| APD356 10 mg b.i.d. APD356-lorcaserin hydrochloride 10 mg twice daily | 201 |
| APD356 10 mg q.d. APD356-lorcaserin hydrochloride 10 mg once daily | 202 |
| Placebo 10 mg b.i.d Placebo 10 mg twice daily | 200 |
| Total | 603 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 5 | 6 | 6 |
| Overall Study | Lost to Follow-up | 10 | 27 | 21 |
| Overall Study | Other | 7 | 3 | 8 |
| Overall Study | Physician Decision | 0 | 2 | 1 |
| Overall Study | Sponsor Decision | 0 | 1 | 1 |
| Overall Study | Withdrawal by Subject | 8 | 16 | 23 |
Baseline characteristics
| Characteristic | APD356 10 mg q.d. | Placebo 10 mg b.i.d | APD356 10 mg b.i.d. | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 2 Participants | 2 Participants | 1 Participants | 5 Participants |
| Age, Categorical Between 18 and 65 years | 200 Participants | 198 Participants | 200 Participants | 598 Participants |
| Age, Continuous | 45.0 years STANDARD_DEVIATION 11.3 | 46.3 years STANDARD_DEVIATION 11.7 | 45.6 years STANDARD_DEVIATION 11.3 | 45.6 years STANDARD_DEVIATION 11.4 |
| Region of Enrollment United States | 202 participants | 200 participants | 201 participants | 603 participants |
| Sex: Female, Male Female | 100 Participants | 118 Participants | 110 Participants | 328 Participants |
| Sex: Female, Male Male | 102 Participants | 82 Participants | 91 Participants | 275 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 70 / 201 | 65 / 202 | 68 / 200 |
| serious Total, serious adverse events | 3 / 201 | 4 / 202 | 1 / 200 |
Outcome results
Primary
Percentage of Participants With Abstinence for the Last 4 Weeks of Treatment From Weeks 9-12
Primary efficacy was assessed as the CO (carbon monoxide)-confirmed continuous abstinence rate for the last 4 weeks of treatment (Month 3: Weeks 9 through 12), defined as no reported smoking (not even a puff) or other nicotine use, verified by end expiratory CO levels \<= 10 ppm.
Time frame: Week 9 - Week 12
Population: Modified Intent-to-Treat: All randomized patients, who received at least 1 dose of study medication, had a baseline measurement, and have a post-randomization measurement
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| APD356 10 mg b.i.d. | Percentage of Participants With Abstinence for the Last 4 Weeks of Treatment From Weeks 9-12 | 15.31 percentage of participants |
| APD356 10 mg q.d. | Percentage of Participants With Abstinence for the Last 4 Weeks of Treatment From Weeks 9-12 | 8.72 percentage of participants |
| Placebo | Percentage of Participants With Abstinence for the Last 4 Weeks of Treatment From Weeks 9-12 | 5.64 percentage of participants |
p-value: 0.002795% CI: [1.47, 6.22]Regression, Logistic
p-value: 0.242795% CI: [0.73, 3.51]Regression, Logistic
p-value: 0.047795% CI: [1.01, 3.56]Regression, Logistic
Secondary
Abstinence During Weeks 3-12
The CO (carbon monoxide)-confirmed continuous abstinence rate for Weeks 3 through 12, defined as no reported smoking (not even a puff) or other nicotine use, verified by end expiratory CO levels \<= 10 ppm
Time frame: Week 3 to Week 12
Population: Modified Intent-to-Treat: All randomized patients, who received at least 1 dose of study medication, had a baseline measurement, and have a post-randomization measurement
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| APD356 10 mg b.i.d. | Abstinence During Weeks 3-12 | 5.61 percentage of participants |
| APD356 10 mg q.d. | Abstinence During Weeks 3-12 | 3.59 percentage of participants |
| Placebo | Abstinence During Weeks 3-12 | 2.05 percentage of participants |
p-value: 0.078495% CI: [0.89, 9.08]Regression, Logistic
p-value: 0.36595% CI: [0.51, 6.17]Regression, Logistic
p-value: 0.343895% CI: [0.61, 4.21]Regression, Logistic
Secondary
Body Weight
Change in body weight from Week 1 (baseline) to Week 12
Time frame: Baseline to Week 12
Population: Modified Intent-to-Treat: All randomized patients, who received at least 1 dose of study medication, had a baseline measurement, and have a post-randomization measurement
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| APD356 10 mg b.i.d. | Body Weight | -0.98 Kg |
| APD356 10 mg q.d. | Body Weight | -0.35 Kg |
| Placebo | Body Weight | -0.01 Kg |
p-value: 0.000495% CI: [-1.51, -0.43]Mixed-effects repeated measures
p-value: 0.226895% CI: [-0.89, 0.21]mixed effects repeated measures
p-value: 0.021795% CI: [-1.17, -0.09]mixed effects repeated measures
Secondary
The 7 Day Point Prevalence or Weekly Abstinence at Week 12
The CO (carbon monoxide)-confirmed continuous abstinence rate at for the 7-day period preceding the Week 12 visit, defined as no reported smoking (not even a puff) or other nicotine use, verified by end expiratory CO levels \<= 10 ppm
Time frame: Week 12
Population: Modified Intent-to-Treat: All randomized patients, who received at least 1 dose of study medication, had a baseline measurement, and have a post-randomization measurement
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| APD356 10 mg b.i.d. | The 7 Day Point Prevalence or Weekly Abstinence at Week 12 | 20.41 percentage of paticipants |
| APD356 10 mg q.d. | The 7 Day Point Prevalence or Weekly Abstinence at Week 12 | 13.85 percentage of paticipants |
| Placebo | The 7 Day Point Prevalence or Weekly Abstinence at Week 12 | 11.79 percentage of paticipants |
p-value: 0.021995% CI: [1.1, 3.35]Regression, Logistic
p-value: 0.54595% CI: [0.66, 2.18]Regression, Logistic
p-value: 0.086895% CI: [0.93, 2.72]Regression, Logistic
Secondary
The 7 Day Point Prevalence or Weekly Abstinence at Week 8
The CO (carbon monoxide)-confirmed continuous abstinence rate at for the 7-day period preceding the Week 8 visit, defined as no reported smoking (not even a puff) or other nicotine use, verified by end expiratory CO levels \<= 10 ppm
Time frame: Week 8
Population: Modified Intent-to-Treat: All randomized patients, who received at least 1 dose of study medication, had a baseline measurement, and have a post-randomization measurement
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| APD356 10 mg b.i.d. | The 7 Day Point Prevalence or Weekly Abstinence at Week 8 | 16.33 percentage of participants |
| APD356 10 mg q.d. | The 7 Day Point Prevalence or Weekly Abstinence at Week 8 | 9.74 percentage of participants |
| Placebo | The 7 Day Point Prevalence or Weekly Abstinence at Week 8 | 9.23 percentage of participants |
p-value: 0.037995% CI: [1.04, 3.55]Regression, Logistic
p-value: 0.862895% CI: [0.54, 2.09]Regression, Logistic
p-value: 0.055695% CI: [0.99, 3.31]Regression, Logistic