Trial Outcomes & Findings for Treatment With Mecamylamine in Smoking and Non-smoking Alcohol Dependent Patients (NCT NCT00342563)

Results Overview

Data were calculated as number of heavy drinking days (heavy drinking days is defined as 5 drinks on a single occasion for men and 4 for women) average during 90 days of treatment.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

136 participants

Primary outcome timeframe

12 weeks

Results posted on

2019-06-04

Participant Flow

Participant milestones

Participant milestones
Measure	Mecamylamine- Smoker mecamylamine: mecamylamine 10mg/day	Mecamylamine Non-Smoker	Placebo Smoker	Placebo Non-Smoker
Overall Study STARTED	41	27	40	28
Overall Study COMPLETED	35	19	26	22
Overall Study NOT COMPLETED	6	8	14	6

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Treatment With Mecamylamine in Smoking and Non-smoking Alcohol Dependent Patients

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Mecamylamine-Smoker n=41 Participants mecamylamine: mecamylamine 10mg/day	Mecamylamine-Non-Smoker n=27 Participants	Placebo-Smoker n=40 Participants Placebo: Placebo	Placebo- Non-Smoker n=28 Participants	Total n=136 Participants Total of all reporting groups
Age, Continuous	45.83 years STANDARD_DEVIATION 8.42 • n=5 Participants	50.93 years STANDARD_DEVIATION 9.55 • n=7 Participants	47.28 years STANDARD_DEVIATION 8.69 • n=5 Participants	51.14 years STANDARD_DEVIATION 10.28 • n=4 Participants	48.4 years STANDARD_DEVIATION 9.3 • n=21 Participants
Sex: Female, Male Female	6 Participants n=5 Participants	4 Participants n=7 Participants	6 Participants n=5 Participants	4 Participants n=4 Participants	20 Participants n=21 Participants
Sex: Female, Male Male	35 Participants n=5 Participants	23 Participants n=7 Participants	34 Participants n=5 Participants	24 Participants n=4 Participants	116 Participants n=21 Participants
Race/Ethnicity, Customized Black	17 participants n=5 Participants	14 participants n=7 Participants	18 participants n=5 Participants	18 participants n=4 Participants	67 participants n=21 Participants
Race/Ethnicity, Customized White	23 participants n=5 Participants	13 participants n=7 Participants	21 participants n=5 Participants	10 participants n=4 Participants	67 participants n=21 Participants
Race/Ethnicity, Customized Other	1 participants n=5 Participants	0 participants n=7 Participants	1 participants n=5 Participants	0 participants n=4 Participants	2 participants n=21 Participants
Veteran Status Veteran	19 participants n=5 Participants	9 participants n=7 Participants	18 participants n=5 Participants	8 participants n=4 Participants	54 participants n=21 Participants
Veteran Status Non-Veteran	22 participants n=5 Participants	18 participants n=7 Participants	22 participants n=5 Participants	20 participants n=4 Participants	82 participants n=21 Participants

PRIMARY outcome

Timeframe: 12 weeks

Data were calculated as number of heavy drinking days (heavy drinking days is defined as 5 drinks on a single occasion for men and 4 for women) average during 90 days of treatment.

Outcome measures

Outcome measures
Measure	Mecamylamine- Smokers n=41 Participants mecamylamine: mecamylamine 10mg/day	Mecamylamine- Non-Smoker n=27 Participants mecamylamine: mecamylamine 10mg/day	Placebo-Smoker n=40 Participants Placebo	Placebo- Non-Smoker n=28 Participants
Percent Heavy Drinking Days During Active Treatment Phase	16.75 days Standard Error 4.33	24.28 days Standard Error 5.30	20.51 days Standard Error 4.57	21.78 days Standard Error 5.11

PRIMARY outcome

Timeframe: 12 weeks

Population: Scores presented are total, and then by subgroup.

The OCDS is a 14-item (rated 0-4), self-administered questionnaire for characterizing and quantifying the obsessive and compulsive cognitive aspects of craving and heavy (alcoholic) drinking, such as drinking-related thought, urges to drink, and the ability to resist those thoughts and urges. A higher total score indicates higher craving and ranges from 0-48.

Outcome measures

Outcome measures
Measure	Mecamylamine- Smokers n=68 Participants mecamylamine: mecamylamine 10mg/day	Mecamylamine- Non-Smoker n=68 Participants mecamylamine: mecamylamine 10mg/day	Placebo-Smoker Placebo	Placebo- Non-Smoker
Self-report Weekly Craving Via Obsessive Compulsive Drinking Scale (OCDS) Total	8.772 units on a scale Standard Error 1.165	8.032 units on a scale Standard Error 1.146	—	—
Self-report Weekly Craving Via Obsessive Compulsive Drinking Scale (OCDS) Smokers	6.969 units on a scale Standard Error 1.713	7.712 units on a scale Standard Error 1.563	—	—
Self-report Weekly Craving Via Obsessive Compulsive Drinking Scale (OCDS) Non-Smokers	10.575 units on a scale Standard Error 1.851	8.352 units on a scale Standard Error 1.676	—	—

PRIMARY outcome

Timeframe: 12 weeks

Population: Smokers only

Questionnaire of smoking urges (QSU). It has 32 questions that range from 1 to 7, there are 8 questions per sub-scale. The total range is 32 to 224. Each sub-scale ranges from 8- 56, with a higher score indicating higher craving.

Outcome measures

Outcome measures
Measure	Mecamylamine- Smokers n=41 Participants mecamylamine: mecamylamine 10mg/day	Mecamylamine- Non-Smoker n=40 Participants mecamylamine: mecamylamine 10mg/day	Placebo-Smoker Placebo	Placebo- Non-Smoker
Self-report Weekly Smoking Craving Desire to Smoke	27.741 units on a scale Standard Error 1.311	28.047 units on a scale Standard Error 1.442	—	—
Self-report Weekly Smoking Craving Anticipation of a positive outcome	28.705 units on a scale Standard Error 1.718	28.273 units on a scale Standard Error 1.857	—	—
Self-report Weekly Smoking Craving Relief	22.557 units on a scale Standard Error 1.604	24.032 units on a scale Standard Error 1.730	—	—
Self-report Weekly Smoking Craving Intention to smoke	31.108 units on a scale Standard Error 1.793	32.549 units on a scale Standard Error 1.946	—	—

PRIMARY outcome

Timeframe: 12 weeks

Population: only smokers

self-report from only the smoking population for cigarettes per day

Outcome measures

Outcome measures
Measure	Mecamylamine- Smokers n=41 Participants mecamylamine: mecamylamine 10mg/day	Mecamylamine- Non-Smoker n=40 Participants mecamylamine: mecamylamine 10mg/day	Placebo-Smoker Placebo	Placebo- Non-Smoker
Self-report Average Number of Cigarettes Per Day	8.055 cigarettes Standard Error 1.163	10.681 cigarettes Standard Error 1.258	—	—

Adverse Events

Mecamylamine Smoker

Serious events: 3 serious events

Other events: 41 other events

Deaths: 0 deaths

Mecamylamine Non-Smoker

Serious events: 0 serious events

Other events: 27 other events

Deaths: 0 deaths

Placebo Smoker

Serious events: 1 serious events

Other events: 40 other events

Deaths: 0 deaths

Placebo Non-Smoker

Serious events: 1 serious events

Other events: 28 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Mecamylamine Smoker n=41 participants at risk mecamylamine: mecamylamine 10mg/day	Mecamylamine Non-Smoker n=27 participants at risk mecamylamine: mecamylamine 10mg/day	Placebo Smoker n=40 participants at risk Placebo: Placebo	Placebo Non-Smoker n=28 participants at risk Placebo: Placebo
Psychiatric disorders Suicidal Ideation	2.4% 1/41 • 12 weeks Adverse events were screened for on a weekly basis. Symptom data were clustered into the following categories: gastrointestinal (GI), central nervous system (CNS), neurological (NE), musculoskeletal (MS), skin, ophthalmological (OPTH), cardio/pulmonary (CAR), and genito-urinary (GU).	0.00% 0/27 • 12 weeks Adverse events were screened for on a weekly basis. Symptom data were clustered into the following categories: gastrointestinal (GI), central nervous system (CNS), neurological (NE), musculoskeletal (MS), skin, ophthalmological (OPTH), cardio/pulmonary (CAR), and genito-urinary (GU).	0.00% 0/40 • 12 weeks Adverse events were screened for on a weekly basis. Symptom data were clustered into the following categories: gastrointestinal (GI), central nervous system (CNS), neurological (NE), musculoskeletal (MS), skin, ophthalmological (OPTH), cardio/pulmonary (CAR), and genito-urinary (GU).	0.00% 0/28 • 12 weeks Adverse events were screened for on a weekly basis. Symptom data were clustered into the following categories: gastrointestinal (GI), central nervous system (CNS), neurological (NE), musculoskeletal (MS), skin, ophthalmological (OPTH), cardio/pulmonary (CAR), and genito-urinary (GU).
Respiratory, thoracic and mediastinal disorders Chest pain	2.4% 1/41 • 12 weeks Adverse events were screened for on a weekly basis. Symptom data were clustered into the following categories: gastrointestinal (GI), central nervous system (CNS), neurological (NE), musculoskeletal (MS), skin, ophthalmological (OPTH), cardio/pulmonary (CAR), and genito-urinary (GU).	0.00% 0/27 • 12 weeks Adverse events were screened for on a weekly basis. Symptom data were clustered into the following categories: gastrointestinal (GI), central nervous system (CNS), neurological (NE), musculoskeletal (MS), skin, ophthalmological (OPTH), cardio/pulmonary (CAR), and genito-urinary (GU).	0.00% 0/40 • 12 weeks Adverse events were screened for on a weekly basis. Symptom data were clustered into the following categories: gastrointestinal (GI), central nervous system (CNS), neurological (NE), musculoskeletal (MS), skin, ophthalmological (OPTH), cardio/pulmonary (CAR), and genito-urinary (GU).	0.00% 0/28 • 12 weeks Adverse events were screened for on a weekly basis. Symptom data were clustered into the following categories: gastrointestinal (GI), central nervous system (CNS), neurological (NE), musculoskeletal (MS), skin, ophthalmological (OPTH), cardio/pulmonary (CAR), and genito-urinary (GU).
Psychiatric disorders Psychotic Delusion	2.4% 1/41 • 12 weeks Adverse events were screened for on a weekly basis. Symptom data were clustered into the following categories: gastrointestinal (GI), central nervous system (CNS), neurological (NE), musculoskeletal (MS), skin, ophthalmological (OPTH), cardio/pulmonary (CAR), and genito-urinary (GU).	0.00% 0/27 • 12 weeks Adverse events were screened for on a weekly basis. Symptom data were clustered into the following categories: gastrointestinal (GI), central nervous system (CNS), neurological (NE), musculoskeletal (MS), skin, ophthalmological (OPTH), cardio/pulmonary (CAR), and genito-urinary (GU).	0.00% 0/40 • 12 weeks Adverse events were screened for on a weekly basis. Symptom data were clustered into the following categories: gastrointestinal (GI), central nervous system (CNS), neurological (NE), musculoskeletal (MS), skin, ophthalmological (OPTH), cardio/pulmonary (CAR), and genito-urinary (GU).	0.00% 0/28 • 12 weeks Adverse events were screened for on a weekly basis. Symptom data were clustered into the following categories: gastrointestinal (GI), central nervous system (CNS), neurological (NE), musculoskeletal (MS), skin, ophthalmological (OPTH), cardio/pulmonary (CAR), and genito-urinary (GU).
Respiratory, thoracic and mediastinal disorders Pneumonia	0.00% 0/41 • 12 weeks Adverse events were screened for on a weekly basis. Symptom data were clustered into the following categories: gastrointestinal (GI), central nervous system (CNS), neurological (NE), musculoskeletal (MS), skin, ophthalmological (OPTH), cardio/pulmonary (CAR), and genito-urinary (GU).	0.00% 0/27 • 12 weeks Adverse events were screened for on a weekly basis. Symptom data were clustered into the following categories: gastrointestinal (GI), central nervous system (CNS), neurological (NE), musculoskeletal (MS), skin, ophthalmological (OPTH), cardio/pulmonary (CAR), and genito-urinary (GU).	2.5% 1/40 • 12 weeks Adverse events were screened for on a weekly basis. Symptom data were clustered into the following categories: gastrointestinal (GI), central nervous system (CNS), neurological (NE), musculoskeletal (MS), skin, ophthalmological (OPTH), cardio/pulmonary (CAR), and genito-urinary (GU).	0.00% 0/28 • 12 weeks Adverse events were screened for on a weekly basis. Symptom data were clustered into the following categories: gastrointestinal (GI), central nervous system (CNS), neurological (NE), musculoskeletal (MS), skin, ophthalmological (OPTH), cardio/pulmonary (CAR), and genito-urinary (GU).
Respiratory, thoracic and mediastinal disorders Chest tightness	0.00% 0/41 • 12 weeks Adverse events were screened for on a weekly basis. Symptom data were clustered into the following categories: gastrointestinal (GI), central nervous system (CNS), neurological (NE), musculoskeletal (MS), skin, ophthalmological (OPTH), cardio/pulmonary (CAR), and genito-urinary (GU).	0.00% 0/27 • 12 weeks Adverse events were screened for on a weekly basis. Symptom data were clustered into the following categories: gastrointestinal (GI), central nervous system (CNS), neurological (NE), musculoskeletal (MS), skin, ophthalmological (OPTH), cardio/pulmonary (CAR), and genito-urinary (GU).	0.00% 0/40 • 12 weeks Adverse events were screened for on a weekly basis. Symptom data were clustered into the following categories: gastrointestinal (GI), central nervous system (CNS), neurological (NE), musculoskeletal (MS), skin, ophthalmological (OPTH), cardio/pulmonary (CAR), and genito-urinary (GU).	3.6% 1/28 • 12 weeks Adverse events were screened for on a weekly basis. Symptom data were clustered into the following categories: gastrointestinal (GI), central nervous system (CNS), neurological (NE), musculoskeletal (MS), skin, ophthalmological (OPTH), cardio/pulmonary (CAR), and genito-urinary (GU).

Other adverse events

Other adverse events
Measure	Mecamylamine Smoker n=41 participants at risk mecamylamine: mecamylamine 10mg/day	Mecamylamine Non-Smoker n=27 participants at risk mecamylamine: mecamylamine 10mg/day	Placebo Smoker n=40 participants at risk Placebo: Placebo	Placebo Non-Smoker n=28 participants at risk Placebo: Placebo
Gastrointestinal disorders gastrointestinal symptoms	70.7% 29/41 • 12 weeks Adverse events were screened for on a weekly basis. Symptom data were clustered into the following categories: gastrointestinal (GI), central nervous system (CNS), neurological (NE), musculoskeletal (MS), skin, ophthalmological (OPTH), cardio/pulmonary (CAR), and genito-urinary (GU).	63.0% 17/27 • 12 weeks Adverse events were screened for on a weekly basis. Symptom data were clustered into the following categories: gastrointestinal (GI), central nervous system (CNS), neurological (NE), musculoskeletal (MS), skin, ophthalmological (OPTH), cardio/pulmonary (CAR), and genito-urinary (GU).	55.0% 22/40 • 12 weeks Adverse events were screened for on a weekly basis. Symptom data were clustered into the following categories: gastrointestinal (GI), central nervous system (CNS), neurological (NE), musculoskeletal (MS), skin, ophthalmological (OPTH), cardio/pulmonary (CAR), and genito-urinary (GU).	64.3% 18/28 • 12 weeks Adverse events were screened for on a weekly basis. Symptom data were clustered into the following categories: gastrointestinal (GI), central nervous system (CNS), neurological (NE), musculoskeletal (MS), skin, ophthalmological (OPTH), cardio/pulmonary (CAR), and genito-urinary (GU).
Nervous system disorders central nervous system symptoms	75.6% 31/41 • 12 weeks Adverse events were screened for on a weekly basis. Symptom data were clustered into the following categories: gastrointestinal (GI), central nervous system (CNS), neurological (NE), musculoskeletal (MS), skin, ophthalmological (OPTH), cardio/pulmonary (CAR), and genito-urinary (GU).	63.0% 17/27 • 12 weeks Adverse events were screened for on a weekly basis. Symptom data were clustered into the following categories: gastrointestinal (GI), central nervous system (CNS), neurological (NE), musculoskeletal (MS), skin, ophthalmological (OPTH), cardio/pulmonary (CAR), and genito-urinary (GU).	47.5% 19/40 • 12 weeks Adverse events were screened for on a weekly basis. Symptom data were clustered into the following categories: gastrointestinal (GI), central nervous system (CNS), neurological (NE), musculoskeletal (MS), skin, ophthalmological (OPTH), cardio/pulmonary (CAR), and genito-urinary (GU).	82.1% 23/28 • 12 weeks Adverse events were screened for on a weekly basis. Symptom data were clustered into the following categories: gastrointestinal (GI), central nervous system (CNS), neurological (NE), musculoskeletal (MS), skin, ophthalmological (OPTH), cardio/pulmonary (CAR), and genito-urinary (GU).

Additional Information

Dr. Elizabeth Ralevski

Yale University School of Medicine

Phone: +1 203-932-5711

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place