Trial Outcomes & Findings for Combining Varenicline and Naltrexone for Smoking Cessation (NCT NCT02698215)

Last Updated: 2021-06-15

Results Overview

Outcome for smoking cessation aim was Expired Carbon Monoxide level, which was used to determine whether a participant successfully abstained from cigarettes. 7 day point prevalence of nicotine abstinence was bioverified by Expired Carbon Monoxide reading of \<= 5ppm at the 26-week follow-up visit.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

165 participants

Primary outcome timeframe

26 weeks post-quit

Results posted on

2021-06-15

Participant Flow

Participant milestones

Participant milestones
Measure	Varenicline Plus Naltrexone VAR (1 mg twice daily) + NTX (50 mg once daily) Varenicline plus Naltrexone: Varenicline 1 mg twice daily plus Naltrexone 50 mg once daily	Varenicline VAR (1 mg twice daily) Varenicline: Varenicline 1 mg twice daily
Overall Study STARTED	83	82
Overall Study COMPLETED	55	64
Overall Study NOT COMPLETED	28	18

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

One participant was missing DSM-5 AUD diagnosis data from the VAR+NTX group.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Varenicline Plus Naltrexone n=83 Participants VAR (1 mg twice daily) + NTX (50 mg once daily) Varenicline plus Naltrexone: Varenicline 1 mg twice daily plus Naltrexone 50 mg once daily	Varenicline n=82 Participants VAR (1 mg twice daily) Varenicline: Varenicline 1 mg twice daily	Total n=165 Participants Total of all reporting groups
Age, Continuous	41.24 years STANDARD_DEVIATION 12.42 • n=83 Participants	42.07 years STANDARD_DEVIATION 11.75 • n=82 Participants	41.55 years STANDARD_DEVIATION 12.06 • n=165 Participants
Sex: Female, Male Female	31 Participants n=83 Participants	32 Participants n=82 Participants	63 Participants n=165 Participants
Sex: Female, Male Male	52 Participants n=83 Participants	50 Participants n=82 Participants	102 Participants n=165 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	12 Participants n=83 Participants	13 Participants n=82 Participants	25 Participants n=165 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	71 Participants n=83 Participants	69 Participants n=82 Participants	140 Participants n=165 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=83 Participants	0 Participants n=82 Participants	0 Participants n=165 Participants
Race (NIH/OMB) American Indian or Alaska Native	2 Participants n=83 Participants	0 Participants n=82 Participants	2 Participants n=165 Participants
Race (NIH/OMB) Asian	3 Participants n=83 Participants	1 Participants n=82 Participants	4 Participants n=165 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	2 Participants n=83 Participants	1 Participants n=82 Participants	3 Participants n=165 Participants
Race (NIH/OMB) Black or African American	40 Participants n=83 Participants	36 Participants n=82 Participants	76 Participants n=165 Participants
Race (NIH/OMB) White	27 Participants n=83 Participants	29 Participants n=82 Participants	56 Participants n=165 Participants
Race (NIH/OMB) More than one race	5 Participants n=83 Participants	7 Participants n=82 Participants	12 Participants n=165 Participants
Race (NIH/OMB) Unknown or Not Reported	4 Participants n=83 Participants	8 Participants n=82 Participants	12 Participants n=165 Participants
Region of Enrollment United States	83 Participants n=83 Participants	82 Participants n=82 Participants	165 Participants n=165 Participants
Smoking Days (Timeline Followback)	28.94 days STANDARD_DEVIATION 3.37 • n=83 Participants	29.39 days STANDARD_DEVIATION 1.49 • n=82 Participants	29.16 days STANDARD_DEVIATION 2.61 • n=165 Participants
Cigarettes per Smoking Day (Timeline Followback)	14.21 cigarettes STANDARD_DEVIATION 8.39 • n=83 Participants	14.10 cigarettes STANDARD_DEVIATION 7.79 • n=82 Participants	14.16 cigarettes STANDARD_DEVIATION 8.07 • n=165 Participants
Expired Alveolar CO Level (ppm)	11.65 ppm STANDARD_DEVIATION 6.25 • n=83 Participants	9.68 ppm STANDARD_DEVIATION 7.34 • n=82 Participants	10.67 ppm STANDARD_DEVIATION 6.86 • n=165 Participants
Urine Cotinine Levels (ng/ml)	5.50 ng/ml STANDARD_DEVIATION 1.14 • n=83 Participants	5.37 ng/ml STANDARD_DEVIATION 1.05 • n=82 Participants	5.44 ng/ml STANDARD_DEVIATION 1.09 • n=165 Participants
Fagerstrom Test for Nicotine Dependence (FTND) Score	4.64 units on a scale STANDARD_DEVIATION 2.26 • n=83 Participants	4.61 units on a scale STANDARD_DEVIATION 2.35 • n=82 Participants	4.63 units on a scale STANDARD_DEVIATION 2.30 • n=165 Participants
Drinking Days (Timeline Followback)	20.71 days STANDARD_DEVIATION 8.08 • n=83 Participants	19.63 days STANDARD_DEVIATION 7.92 • n=82 Participants	20.17 days STANDARD_DEVIATION 8.00 • n=165 Participants
Drinks per Drinking Day (Timeline Followback)	6.50 drinks per drinking day STANDARD_DEVIATION 4.65 • n=83 Participants	6.44 drinks per drinking day STANDARD_DEVIATION 3.76 • n=82 Participants	6.47 drinks per drinking day STANDARD_DEVIATION 4.22 • n=165 Participants
Heavy Drinking Days (Timeline Followback)	12.87 heavy drinking days STANDARD_DEVIATION 9.55 • n=83 Participants	12.30 heavy drinking days STANDARD_DEVIATION 8.84 • n=82 Participants	12.59 heavy drinking days STANDARD_DEVIATION 9.18 • n=165 Participants
Alcohol Use Disorder Severity (Structured Clinical Interview for DSM-5) None	24 Participants n=82 Participants • One participant was missing DSM-5 AUD diagnosis data from the VAR+NTX group.	24 Participants n=82 Participants • One participant was missing DSM-5 AUD diagnosis data from the VAR+NTX group.	48 Participants n=164 Participants • One participant was missing DSM-5 AUD diagnosis data from the VAR+NTX group.
Alcohol Use Disorder Severity (Structured Clinical Interview for DSM-5) Mild	27 Participants n=82 Participants • One participant was missing DSM-5 AUD diagnosis data from the VAR+NTX group.	22 Participants n=82 Participants • One participant was missing DSM-5 AUD diagnosis data from the VAR+NTX group.	49 Participants n=164 Participants • One participant was missing DSM-5 AUD diagnosis data from the VAR+NTX group.
Alcohol Use Disorder Severity (Structured Clinical Interview for DSM-5) Moderate	19 Participants n=82 Participants • One participant was missing DSM-5 AUD diagnosis data from the VAR+NTX group.	23 Participants n=82 Participants • One participant was missing DSM-5 AUD diagnosis data from the VAR+NTX group.	42 Participants n=164 Participants • One participant was missing DSM-5 AUD diagnosis data from the VAR+NTX group.
Alcohol Use Disorder Severity (Structured Clinical Interview for DSM-5) Severe	12 Participants n=82 Participants • One participant was missing DSM-5 AUD diagnosis data from the VAR+NTX group.	13 Participants n=82 Participants • One participant was missing DSM-5 AUD diagnosis data from the VAR+NTX group.	25 Participants n=164 Participants • One participant was missing DSM-5 AUD diagnosis data from the VAR+NTX group.

PRIMARY outcome

Timeframe: 26 weeks post-quit

Population: Intent to Treat.

Outcome measures

Outcome measures
Measure	Varenicline Plus Naltrexone n=83 Participants VAR (1 mg twice daily) + NTX (50 mg once daily) Varenicline plus Naltrexone: Varenicline 1 mg twice daily plus Naltrexone 50 mg once daily	Varenicline n=82 Participants VAR (1 mg twice daily) Varenicline: Varenicline 1 mg twice daily
Number of Participants With Expired Carbon Monoxide Level <=5ppm	22 Participants	37 Participants

SECONDARY outcome

Timeframe: 26 weeks post-quit

Population: Intent to Treat

Outcome for drinking reduction aim - Number of Drinks per Drinking Day

Outcome measures

Outcome measures
Measure	Varenicline Plus Naltrexone n=83 Participants VAR (1 mg twice daily) + NTX (50 mg once daily) Varenicline plus Naltrexone: Varenicline 1 mg twice daily plus Naltrexone 50 mg once daily	Varenicline n=82 Participants VAR (1 mg twice daily) Varenicline: Varenicline 1 mg twice daily
Drinks Per Drinking Day	3.1242 drinks per drinking day Standard Error 1.0281	3.5121 drinks per drinking day Standard Error .9594

Adverse Events

Varenicline Plus Naltrexone

Serious events: 0 serious events

Other events: 63 other events

Deaths: 0 deaths

Varenicline

Serious events: 0 serious events

Other events: 64 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Lara Ray, PhD

University of California Los Angeles

Phone: 310-794-5383

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Other adverse events
Measure	Varenicline Plus Naltrexone n=83 participants at risk VAR (1 mg twice daily) + NTX (50 mg once daily) Varenicline plus Naltrexone: Varenicline 1 mg twice daily plus Naltrexone 50 mg once daily	Varenicline n=82 participants at risk VAR (1 mg twice daily) Varenicline: Varenicline 1 mg twice daily
Nervous system disorders seizure	0.00% 0/83 • Adverse event data were collected at each in-person visit (6 visits) during the medication period (approximately 12 weeks or 3 months).	1.2% 1/82 • Number of events 1 • Adverse event data were collected at each in-person visit (6 visits) during the medication period (approximately 12 weeks or 3 months).
Gastrointestinal disorders nausea	45.8% 38/83 • Number of events 39 • Adverse event data were collected at each in-person visit (6 visits) during the medication period (approximately 12 weeks or 3 months).	34.1% 28/82 • Number of events 29 • Adverse event data were collected at each in-person visit (6 visits) during the medication period (approximately 12 weeks or 3 months).
Gastrointestinal disorders vomiting	9.6% 8/83 • Number of events 9 • Adverse event data were collected at each in-person visit (6 visits) during the medication period (approximately 12 weeks or 3 months).	13.4% 11/82 • Number of events 12 • Adverse event data were collected at each in-person visit (6 visits) during the medication period (approximately 12 weeks or 3 months).
Gastrointestinal disorders constipation	6.0% 5/83 • Number of events 5 • Adverse event data were collected at each in-person visit (6 visits) during the medication period (approximately 12 weeks or 3 months).	3.7% 3/82 • Number of events 4 • Adverse event data were collected at each in-person visit (6 visits) during the medication period (approximately 12 weeks or 3 months).
Gastrointestinal disorders diarrhea	4.8% 4/83 • Number of events 4 • Adverse event data were collected at each in-person visit (6 visits) during the medication period (approximately 12 weeks or 3 months).	3.7% 3/82 • Number of events 3 • Adverse event data were collected at each in-person visit (6 visits) during the medication period (approximately 12 weeks or 3 months).
Gastrointestinal disorders upset stomach	3.6% 3/83 • Number of events 4 • Adverse event data were collected at each in-person visit (6 visits) during the medication period (approximately 12 weeks or 3 months).	9.8% 8/82 • Number of events 9 • Adverse event data were collected at each in-person visit (6 visits) during the medication period (approximately 12 weeks or 3 months).
Gastrointestinal disorders decreased appetite	4.8% 4/83 • Number of events 4 • Adverse event data were collected at each in-person visit (6 visits) during the medication period (approximately 12 weeks or 3 months).	0.00% 0/82 • Adverse event data were collected at each in-person visit (6 visits) during the medication period (approximately 12 weeks or 3 months).
Gastrointestinal disorders increased appetite	1.2% 1/83 • Number of events 1 • Adverse event data were collected at each in-person visit (6 visits) during the medication period (approximately 12 weeks or 3 months).	0.00% 0/82 • Adverse event data were collected at each in-person visit (6 visits) during the medication period (approximately 12 weeks or 3 months).
Gastrointestinal disorders decreased bowel movements	1.2% 1/83 • Number of events 1 • Adverse event data were collected at each in-person visit (6 visits) during the medication period (approximately 12 weeks or 3 months).	0.00% 0/82 • Adverse event data were collected at each in-person visit (6 visits) during the medication period (approximately 12 weeks or 3 months).
Gastrointestinal disorders acid reflux	0.00% 0/83 • Adverse event data were collected at each in-person visit (6 visits) during the medication period (approximately 12 weeks or 3 months).	1.2% 1/82 • Number of events 1 • Adverse event data were collected at each in-person visit (6 visits) during the medication period (approximately 12 weeks or 3 months).
Nervous system disorders headache	18.1% 15/83 • Number of events 17 • Adverse event data were collected at each in-person visit (6 visits) during the medication period (approximately 12 weeks or 3 months).	9.8% 8/82 • Number of events 10 • Adverse event data were collected at each in-person visit (6 visits) during the medication period (approximately 12 weeks or 3 months).
Nervous system disorders migraine	1.2% 1/83 • Number of events 1 • Adverse event data were collected at each in-person visit (6 visits) during the medication period (approximately 12 weeks or 3 months).	0.00% 0/82 • Adverse event data were collected at each in-person visit (6 visits) during the medication period (approximately 12 weeks or 3 months).
Nervous system disorders loss of consciousness	0.00% 0/83 • Adverse event data were collected at each in-person visit (6 visits) during the medication period (approximately 12 weeks or 3 months).	1.2% 1/82 • Number of events 1 • Adverse event data were collected at each in-person visit (6 visits) during the medication period (approximately 12 weeks or 3 months).
Nervous system disorders dizziness	1.2% 1/83 • Number of events 1 • Adverse event data were collected at each in-person visit (6 visits) during the medication period (approximately 12 weeks or 3 months).	2.4% 2/82 • Number of events 2 • Adverse event data were collected at each in-person visit (6 visits) during the medication period (approximately 12 weeks or 3 months).
Psychiatric disorders depression	7.2% 6/83 • Number of events 6 • Adverse event data were collected at each in-person visit (6 visits) during the medication period (approximately 12 weeks or 3 months).	1.2% 1/82 • Number of events 1 • Adverse event data were collected at each in-person visit (6 visits) during the medication period (approximately 12 weeks or 3 months).
Psychiatric disorders abnormal dreams	15.7% 13/83 • Number of events 13 • Adverse event data were collected at each in-person visit (6 visits) during the medication period (approximately 12 weeks or 3 months).	20.7% 17/82 • Number of events 18 • Adverse event data were collected at each in-person visit (6 visits) during the medication period (approximately 12 weeks or 3 months).
Psychiatric disorders anxiety	3.6% 3/83 • Number of events 3 • Adverse event data were collected at each in-person visit (6 visits) during the medication period (approximately 12 weeks or 3 months).	3.7% 3/82 • Number of events 3 • Adverse event data were collected at each in-person visit (6 visits) during the medication period (approximately 12 weeks or 3 months).
Psychiatric disorders mood swings	1.2% 1/83 • Number of events 1 • Adverse event data were collected at each in-person visit (6 visits) during the medication period (approximately 12 weeks or 3 months).	0.00% 0/82 • Adverse event data were collected at each in-person visit (6 visits) during the medication period (approximately 12 weeks or 3 months).
Endocrine disorders dry mouth	3.6% 3/83 • Number of events 3 • Adverse event data were collected at each in-person visit (6 visits) during the medication period (approximately 12 weeks or 3 months).	2.4% 2/82 • Number of events 2 • Adverse event data were collected at each in-person visit (6 visits) during the medication period (approximately 12 weeks or 3 months).
Endocrine disorders low blood sugar	0.00% 0/83 • Adverse event data were collected at each in-person visit (6 visits) during the medication period (approximately 12 weeks or 3 months).	1.2% 1/82 • Number of events 1 • Adverse event data were collected at each in-person visit (6 visits) during the medication period (approximately 12 weeks or 3 months).
Endocrine disorders borderline diabetes	1.2% 1/83 • Number of events 1 • Adverse event data were collected at each in-person visit (6 visits) during the medication period (approximately 12 weeks or 3 months).	0.00% 0/82 • Adverse event data were collected at each in-person visit (6 visits) during the medication period (approximately 12 weeks or 3 months).
Endocrine disorders hyperglycemia	1.2% 1/83 • Number of events 1 • Adverse event data were collected at each in-person visit (6 visits) during the medication period (approximately 12 weeks or 3 months).	0.00% 0/82 • Adverse event data were collected at each in-person visit (6 visits) during the medication period (approximately 12 weeks or 3 months).
Ear and labyrinth disorders earache	0.00% 0/83 • Adverse event data were collected at each in-person visit (6 visits) during the medication period (approximately 12 weeks or 3 months).	1.2% 1/82 • Number of events 1 • Adverse event data were collected at each in-person visit (6 visits) during the medication period (approximately 12 weeks or 3 months).
Ear and labyrinth disorders ear infection	1.2% 1/83 • Number of events 1 • Adverse event data were collected at each in-person visit (6 visits) during the medication period (approximately 12 weeks or 3 months).	1.2% 1/82 • Number of events 1 • Adverse event data were collected at each in-person visit (6 visits) during the medication period (approximately 12 weeks or 3 months).
Ear and labyrinth disorders tinnitus	0.00% 0/83 • Adverse event data were collected at each in-person visit (6 visits) during the medication period (approximately 12 weeks or 3 months).	1.2% 1/82 • Number of events 1 • Adverse event data were collected at each in-person visit (6 visits) during the medication period (approximately 12 weeks or 3 months).
Blood and lymphatic system disorders bloody nose	0.00% 0/83 • Adverse event data were collected at each in-person visit (6 visits) during the medication period (approximately 12 weeks or 3 months).	1.2% 1/82 • Number of events 1 • Adverse event data were collected at each in-person visit (6 visits) during the medication period (approximately 12 weeks or 3 months).
Blood and lymphatic system disorders anemia	0.00% 0/83 • Adverse event data were collected at each in-person visit (6 visits) during the medication period (approximately 12 weeks or 3 months).	1.2% 1/82 • Number of events 1 • Adverse event data were collected at each in-person visit (6 visits) during the medication period (approximately 12 weeks or 3 months).
Infections and infestations sinus infection	1.2% 1/83 • Number of events 1 • Adverse event data were collected at each in-person visit (6 visits) during the medication period (approximately 12 weeks or 3 months).	0.00% 0/82 • Adverse event data were collected at each in-person visit (6 visits) during the medication period (approximately 12 weeks or 3 months).
Infections and infestations flu	2.4% 2/83 • Number of events 2 • Adverse event data were collected at each in-person visit (6 visits) during the medication period (approximately 12 weeks or 3 months).	6.1% 5/82 • Number of events 5 • Adverse event data were collected at each in-person visit (6 visits) during the medication period (approximately 12 weeks or 3 months).
Infections and infestations cold	4.8% 4/83 • Number of events 4 • Adverse event data were collected at each in-person visit (6 visits) during the medication period (approximately 12 weeks or 3 months).	14.6% 12/82 • Number of events 12 • Adverse event data were collected at each in-person visit (6 visits) during the medication period (approximately 12 weeks or 3 months).
Infections and infestations respiratory infection	1.2% 1/83 • Number of events 1 • Adverse event data were collected at each in-person visit (6 visits) during the medication period (approximately 12 weeks or 3 months).	0.00% 0/82 • Adverse event data were collected at each in-person visit (6 visits) during the medication period (approximately 12 weeks or 3 months).
Infections and infestations fever	1.2% 1/83 • Number of events 1 • Adverse event data were collected at each in-person visit (6 visits) during the medication period (approximately 12 weeks or 3 months).	3.7% 3/82 • Number of events 3 • Adverse event data were collected at each in-person visit (6 visits) during the medication period (approximately 12 weeks or 3 months).
Infections and infestations runny nose	0.00% 0/83 • Adverse event data were collected at each in-person visit (6 visits) during the medication period (approximately 12 weeks or 3 months).	1.2% 1/82 • Number of events 1 • Adverse event data were collected at each in-person visit (6 visits) during the medication period (approximately 12 weeks or 3 months).
Cardiac disorders elevated blood pressure	1.2% 1/83 • Number of events 1 • Adverse event data were collected at each in-person visit (6 visits) during the medication period (approximately 12 weeks or 3 months).	1.2% 1/82 • Number of events 1 • Adverse event data were collected at each in-person visit (6 visits) during the medication period (approximately 12 weeks or 3 months).
Cardiac disorders cardiac event	1.2% 1/83 • Number of events 1 • Adverse event data were collected at each in-person visit (6 visits) during the medication period (approximately 12 weeks or 3 months).	1.2% 1/82 • Number of events 1 • Adverse event data were collected at each in-person visit (6 visits) during the medication period (approximately 12 weeks or 3 months).
Cardiac disorders rapid heartbeat	2.4% 2/83 • Number of events 2 • Adverse event data were collected at each in-person visit (6 visits) during the medication period (approximately 12 weeks or 3 months).	0.00% 0/82 • Adverse event data were collected at each in-person visit (6 visits) during the medication period (approximately 12 weeks or 3 months).
Respiratory, thoracic and mediastinal disorders difficulty breathing	0.00% 0/83 • Adverse event data were collected at each in-person visit (6 visits) during the medication period (approximately 12 weeks or 3 months).	1.2% 1/82 • Number of events 1 • Adverse event data were collected at each in-person visit (6 visits) during the medication period (approximately 12 weeks or 3 months).
Respiratory, thoracic and mediastinal disorders cough	2.4% 2/83 • Number of events 2 • Adverse event data were collected at each in-person visit (6 visits) during the medication period (approximately 12 weeks or 3 months).	0.00% 0/82 • Adverse event data were collected at each in-person visit (6 visits) during the medication period (approximately 12 weeks or 3 months).
Respiratory, thoracic and mediastinal disorders chest discomfort	1.2% 1/83 • Number of events 1 • Adverse event data were collected at each in-person visit (6 visits) during the medication period (approximately 12 weeks or 3 months).	1.2% 1/82 • Number of events 1 • Adverse event data were collected at each in-person visit (6 visits) during the medication period (approximately 12 weeks or 3 months).
Respiratory, thoracic and mediastinal disorders sore throat	0.00% 0/83 • Adverse event data were collected at each in-person visit (6 visits) during the medication period (approximately 12 weeks or 3 months).	1.2% 1/82 • Number of events 1 • Adverse event data were collected at each in-person visit (6 visits) during the medication period (approximately 12 weeks or 3 months).