Trial Outcomes & Findings for Effects of Naltrexone on Nicotine Reinforcement (NCT NCT00270231)

NCT ID: NCT00270231

Last Updated: 2013-12-10

Results Overview

On day 4 of each study medication period, participants completed a cigarette choice procedure where the subject is asked to take 4 puffs from a nicotinized (nicotine-containing) or a denicotinized (no nicotine) cigarette every 30 minutes for 2 hours (maximum of 24 puffs). The outcome variable is the number of nicotine cigarette choices or puffs out of 24 total puffs during these cigarette choice procedures. Subjects who had the A/A genotype took an average of 18.5 puffs from the nicotine-containing cigarettes. Subjects with the A/G or G/G genotypes took an average of 16.2 puffs from the nicotine-containing cigarettes.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 64 participants
• Primary outcome timeframe: 2 hours
• Results posted on: 2013-12-10

Participant Flow

Recruitment occurred from March 2004 to August 2005. All subject sessions occurred at the Tobacco Use Research Center's lab, the Biobehavioral Lab (BBL), at the University of Pennsylvania.

The primary genotype of interest was the functional mu opioid receptor (OPRM1). Smokers with the Asp40 variant (A/G or G/G genotypes; about 27% of smokers) were oversampled, relative to those with the more common Asn40 variant (A/A genotype; 73% of smokers), in order to have an equal number of participants in each genotype group.

Participant milestones

Measure	Naltrexone, Then Placebo These participants took active naltrexone during their first 4-day study period. The dosing for naltrexone was the same for all participants. Day 1 = 12.5mg, Day 2 = 25mg, Days 3 \& 4 = 50mg. They received placebo (sugar pill) during the second 4-day study period.	Placebo, Then Naltrexone These participants took placebo (sugar pill) during their first 4-day study period. They received active naltrexone during the second 4-day study period. The dosing for naltrexone was the same for all participants. Day 1 = 12.5mg, Day 2 = 25mg, Days 3 \& 4 = 50mg.
First Intervention STARTED	32	32
First Intervention COMPLETED	31	31
First Intervention NOT COMPLETED	1	1
Washout Period STARTED	31	31
Washout Period COMPLETED	30	31
Washout Period NOT COMPLETED	1	0
Second Intervention STARTED	30	31
Second Intervention COMPLETED	30	30
Second Intervention NOT COMPLETED	0	1

Reasons for withdrawal

Measure	Naltrexone, Then Placebo These participants took active naltrexone during their first 4-day study period. The dosing for naltrexone was the same for all participants. Day 1 = 12.5mg, Day 2 = 25mg, Days 3 \& 4 = 50mg. They received placebo (sugar pill) during the second 4-day study period.	Placebo, Then Naltrexone These participants took placebo (sugar pill) during their first 4-day study period. They received active naltrexone during the second 4-day study period. The dosing for naltrexone was the same for all participants. Day 1 = 12.5mg, Day 2 = 25mg, Days 3 \& 4 = 50mg.
First Intervention Lost to Follow-up	1	1
Washout Period Lost to Follow-up	1	0
Second Intervention Lost to Follow-up	0	1

Baseline Characteristics

Effects of Naltrexone on Nicotine Reinforcement

Baseline characteristics by cohort

Measure	Entire Study Population n=64 Participants Includes subjects with both OPRM1 genotypes (Asp40 (A/G or G/G allele vs. Asn40 (A/A) allele) who started Intervention Period 1.
Age, Categorical <=18 years	1 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	59 Participants n=5 Participants
Age, Categorical >=65 years	4 Participants n=5 Participants
Age Continuous	43.2 years STANDARD_DEVIATION 15.0 • n=5 Participants
Sex: Female, Male Female	26 Participants n=5 Participants
Sex: Female, Male Male	38 Participants n=5 Participants
Region of Enrollment United States	64 participants n=5 Participants

PRIMARY outcome

Timeframe: 2 hours

Population: Participants were analyzed with respect to genotype regardless of intervention.

On day 4 of each study medication period, participants completed a cigarette choice procedure where the subject is asked to take 4 puffs from a nicotinized (nicotine-containing) or a denicotinized (no nicotine) cigarette every 30 minutes for 2 hours (maximum of 24 puffs). The outcome variable is the number of nicotine cigarette choices or puffs out of 24 total puffs during these cigarette choice procedures.

Subjects who had the A/A genotype took an average of 18.5 puffs from the nicotine-containing cigarettes. Subjects with the A/G or G/G genotypes took an average of 16.2 puffs from the nicotine-containing cigarettes.

Outcome measures

Measure	OPRM1 Genotype - A/A n=30 Participants Participants who have the Asn40 OPRM1=A/A	OPRM1 Genotype - A/G or G/G n=30 Participants Participants who have the Asp40 OPRM1=A/G or G/G
Number of Nicotine Cigarette Choices Taken During the Cigarette Choice Procedure.	18.5 Number of Nicotine Cigarette Puffs Taken Standard Deviation 4.2	16.2 Number of Nicotine Cigarette Puffs Taken Standard Deviation 6.2

Adverse Events

Naltrexone Only

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Placebo Only

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Caryn Lerman, Ph.D.

University of Pennsylvania

Phone: 215-746-7141

Email: clerman@mail.med.upenn.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place