Trial Outcomes & Findings for Metabolism of NNK in Japanese Americans (NCT NCT04228952)

NCT ID: NCT04228952

Last Updated: 2025-08-01

Results Overview

Difference in means of the ratio of D4-hydroxy acid to D4- NNAL (an estimate if NNK alpha hydroxylation) for the two groups (null versus average CYP2A6 activity)

Recruitment status

COMPLETED

Target enrollment

16 participants

Primary outcome timeframe

7 days

Results posted on

2025-08-01

Participant Flow

Participant milestones

Participant milestones
Measure
Smokers With Very Low or no CYP2A6 Activity
Japanese American smokers (daily \> 5 cigarettes) with little or no CYP2A6 activity (CYP2A6 activity defined as a ratio of trans-3-hydroxycotinine:cotinine ratio of \<0.6). Modified Natural American Spirit-Tan or Green cigarettes injected with labeled NNK: American Spirit cigarettes will be modified by adding 0.300 μg \[pyridine-D4\]NNK to each cigarette so that the amount of total (deuterated plus unlabeled) NNK in these cigarettes is below 0.700 μg/g tobacco.
Smokers With High CYP2A6 Activity
Japanese American smokers (daily \> 5 cigarettes) with high CYP2A6 activity (CYP2A6 activity defined as a ratio of trans-3-hydroxycotinine:cotinine ratio of \> 3.0) Modified Natural American Spirit-Tan or Green cigarettes injected with labeled NNK: American Spirit cigarettes will be modified by adding 0.300 μg \[pyridine-D4\]NNK to each cigarette so that the amount of total (deuterated plus unlabeled) NNK in these cigarettes is below 0.700 μg/g tobacco.
Overall Study
STARTED
8
8
Overall Study
COMPLETED
8
8
Overall Study
NOT COMPLETED
0
0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Metabolism of NNK in Japanese Americans

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Smokers With Very Low or no CYP2A6 Activity
n=8 Participants
Japanese American smokers (daily \> 5 cigarettes) with little or no CYP2A6 activity (CYP2A6 activity defined as a ratio of trans-3-hydroxycotinine:cotinine ratio of \<0.6). Modified Natural American Spirit-Tan or Green cigarettes injected with labeled NNK: American Spirit cigarettes will be modified by adding 0.300 μg \[pyridine-D4\]NNK to each cigarette so that the amount of total (deuterated plus unlabeled) NNK in these cigarettes is below 0.700 μg/g tobacco.
Smokers With High CYP2A6 Activity
n=8 Participants
Japanese American smokers (daily \> 5 cigarettes) with high CYP2A6 activity (CYP2A6 activity defined as a ratio of trans-3-hydroxycotinine:cotinine ratio of \> 3.0) Modified Natural American Spirit-Tan or Green cigarettes injected with labeled NNK: American Spirit cigarettes will be modified by adding 0.300 μg \[pyridine-D4\]NNK to each cigarette so that the amount of total (deuterated plus unlabeled) NNK in these cigarettes is below 0.700 μg/g tobacco.
Total
n=16 Participants
Total of all reporting groups
Age, Categorical
<=18 years
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
Age, Categorical
Between 18 and 65 years
8 Participants
n=5 Participants
8 Participants
n=7 Participants
16 Participants
n=5 Participants
Age, Categorical
>=65 years
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
Sex: Female, Male
Female
3 Participants
n=5 Participants
7 Participants
n=7 Participants
10 Participants
n=5 Participants
Sex: Female, Male
Male
5 Participants
n=5 Participants
1 Participants
n=7 Participants
6 Participants
n=5 Participants
Race (NIH/OMB)
American Indian or Alaska Native
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
Race (NIH/OMB)
Asian
6 Participants
n=5 Participants
6 Participants
n=7 Participants
12 Participants
n=5 Participants
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
2 Participants
n=5 Participants
2 Participants
n=7 Participants
4 Participants
n=5 Participants
Race (NIH/OMB)
Black or African American
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
Race (NIH/OMB)
White
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
Race (NIH/OMB)
More than one race
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
Race (NIH/OMB)
Unknown or Not Reported
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
Region of Enrollment
United States
8 participants
n=5 Participants
8 participants
n=7 Participants
16 participants
n=5 Participants

PRIMARY outcome

Timeframe: 7 days

Difference in means of the ratio of D4-hydroxy acid to D4- NNAL (an estimate if NNK alpha hydroxylation) for the two groups (null versus average CYP2A6 activity)

Outcome measures

Outcome measures
Measure
Smokers With Very Low or no CYP2A6 Activity
n=8 Participants
Japanese American smokers (daily \> 5 cigarettes) with little or no CYP2A6 activity (CYP2A6 activity defined as a ratio of trans-3-hydroxycotinine:cotinine ratio of \<0.6). Modified Natural American Spirit-Tan or Green cigarettes injected with labeled NNK: American Spirit cigarettes will be modified by adding 0.300 μg \[pyridine-D4\]NNK to each cigarette so that the amount of total (deuterated plus unlabeled) NNK in these cigarettes is below 0.700 μg/g tobacco.
Smokers With High CYP2A6 Activity
n=8 Participants
Japanese American smokers (daily \> 5 cigarettes) with high CYP2A6 activity (CYP2A6 activity defined as a ratio of trans-3-hydroxycotinine:cotinine ratio of \> 3.0) Modified Natural American Spirit-Tan or Green cigarettes injected with labeled NNK: American Spirit cigarettes will be modified by adding 0.300 μg \[pyridine-D4\]NNK to each cigarette so that the amount of total (deuterated plus unlabeled) NNK in these cigarettes is below 0.700 μg/g tobacco.
The Ratio of D4-hydroxy Acid to D4- NNAL (an Estimate if NNK Alpha Hydroxylation)
0.133 Ratio
Standard Deviation 0.096
0.175 Ratio
Standard Deviation 0.066

Adverse Events

Smokers With Very Low or no CYP2A6 Activity

Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths

Smokers With High CYP2A6 Activity

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

Susan Murphy, PhD

Masonic Cancer Center

Phone: 612-624-7633

Results disclosure agreements

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