Trial Outcomes & Findings for Developmental Regulation of Proteins Responsible for Transforming Drugs in the Body (NCT NCT00117715)

Last Updated: 2017-09-12

Results Overview

Concentrations of dextromethorphan(DM) and it's metabolite dextrorphan (DX) are quantified in urine and used to estimate the activity of cytochromes P450 2D6 using the well established DM/DX ratio. The longitudinal study design allows for changes in drug metabolism activity as a function of age which can be characterized via least squares regression where the slope of age vs. DM/DX ratio is examined for deviations from zero.

Recruitment status

COMPLETED

Target enrollment

121 participants

Primary outcome timeframe

every 6 months for 5 years

Results posted on

2017-09-12

Participant Flow

Participant milestones

Participant milestones
Measure	Longitudinal Assessment Cohort Normal healthy children approximately one year of age followed through five years of age to evaluate the ontogeny of CYP1A2, CYP2D6, CYP3A4.
Overall Study STARTED	121
Overall Study 1 Year	88
Overall Study 1.5 Year	85
Overall Study 2 Year	76
Overall Study 2.5 Year	70
Overall Study 3 Year	61
Overall Study 3.5 Year	60
Overall Study 4 Year	58
Overall Study 4.5 Year	55
Overall Study 5 Year	49
Overall Study COMPLETED	49
Overall Study NOT COMPLETED	72

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Developmental Regulation of Proteins Responsible for Transforming Drugs in the Body

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Longitudinal Assessment Cohort n=111 Participants Normal healthy children approximately one year of age followed through five years of age to evaluate the ontogeny of CYP1A2, CYP2D6, CYP3A4.
Age, Continuous	1.21 years STANDARD_DEVIATION 0.28 • n=5 Participants
Sex: Female, Male Female	52 Participants n=5 Participants
Sex: Female, Male Male	59 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	4 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	107 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	58 Participants n=5 Participants
Race (NIH/OMB) White	46 Participants n=5 Participants
Race (NIH/OMB) More than one race	6 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: every 6 months for 5 years

Population: Participants completing each milestone visit at each 0.5 years of age.

Outcome measures

Outcome measures
Measure	Longitudinal Assessment Cohort n=111 Participants Normal healthy children approximately one year of age followed through five years of age to evaluate the ontogeny of CYP1A2, CYP2D6, CYP3A4.
Change in CYP2D6 Drug Metabolism Phenotype With Age Log (DM/DX) Milestone 1	-1.974 unitless ratio Standard Deviation 0.593
Change in CYP2D6 Drug Metabolism Phenotype With Age Log (DM/DX) Milestone 2	-2.083 unitless ratio Standard Deviation 0.617
Change in CYP2D6 Drug Metabolism Phenotype With Age Log (DM/DX) Milestone 3	-2.162 unitless ratio Standard Deviation 0.638
Change in CYP2D6 Drug Metabolism Phenotype With Age Log (DM/DX) Milestone 4	-2.073 unitless ratio Standard Deviation 0.657
Change in CYP2D6 Drug Metabolism Phenotype With Age Log (DM/DX) Milestone 5	-2.161 unitless ratio Standard Deviation 0.669
Change in CYP2D6 Drug Metabolism Phenotype With Age Log (DM/DX) Milestone 6	-2.185 unitless ratio Standard Deviation 0.670
Change in CYP2D6 Drug Metabolism Phenotype With Age Log (DM/DX) Milestone 7	-2.284 unitless ratio Standard Deviation 0.745
Change in CYP2D6 Drug Metabolism Phenotype With Age Log (DM/DX) Milestone 8	-2.177 unitless ratio Standard Deviation 0.699
Change in CYP2D6 Drug Metabolism Phenotype With Age Log (DM/DX) Milestone 9	-2.384 unitless ratio Standard Deviation 0.672

PRIMARY outcome

Timeframe: every 6 months for 5 years

Population: Participants completing each milestone visit at each 0.5 years of age.

Concentrations of dextromethorphan (DM) metabolites 3-hydroxymorphinan (3HM) and dextrorphan (DX) are quantified in urine and used to estimate the activity of cytochrome P450 3A4 using the well established 3HM/DX ratio. The longitudinal study design allows for changes in drug metabolism activity as a function of age which can be characterized via least squares regression where the slope of age vs. 3HM/DX ratio is examined for deviations from zero.

Outcome measures

Outcome measures
Measure	Longitudinal Assessment Cohort n=111 Participants Normal healthy children approximately one year of age followed through five years of age to evaluate the ontogeny of CYP1A2, CYP2D6, CYP3A4.
Change in CYP3A4 Drug Metabolism Phenotype With Age Log (3HM/DX) Milestone 1	-0.069 unitless ratio Standard Deviation 0.180
Change in CYP3A4 Drug Metabolism Phenotype With Age Log (3HM/DX) Milestone 2	-0.117 unitless ratio Standard Deviation 0.194
Change in CYP3A4 Drug Metabolism Phenotype With Age Log (3HM/DX) Milestone 3	-0.142 unitless ratio Standard Deviation 0.223
Change in CYP3A4 Drug Metabolism Phenotype With Age Log (3HM/DX) Milestone 4	-0.158 unitless ratio Standard Deviation 0.276
Change in CYP3A4 Drug Metabolism Phenotype With Age Log (3HM/DX) Milestone 5	-0.109 unitless ratio Standard Deviation 0.201
Change in CYP3A4 Drug Metabolism Phenotype With Age Log (3HM/DX) Milestone 6	-0.136 unitless ratio Standard Deviation 0.194
Change in CYP3A4 Drug Metabolism Phenotype With Age Log (3HM/DX) Milestone 7	-0.133 unitless ratio Standard Deviation 0.164
Change in CYP3A4 Drug Metabolism Phenotype With Age Log (3HM/DX) Milestone 8	-0.122 unitless ratio Standard Deviation 0.202
Change in CYP3A4 Drug Metabolism Phenotype With Age Log (3HM/DX) Milestone 9	-0.169 unitless ratio Standard Deviation 0.218

PRIMARY outcome

Timeframe: every 6 months for 5 years

Population: Participants completing each milestone visit at each 0.5 years of age.

Concentrations of caffeine metabolites 5-Acetylamino-6-amino-3-methyluracil (AAMU), 1-methylxanthine (1MX), 1-methyluric acid (1MU), and 1,7-dimethyluric acid (17MU) are quantified in urine and used to estimate the activity of cytochrome P450 1A2 using the well established (AAMU+1MX+1MU)/1,7U ratio. The longitudinal study design allows for changes in drug metabolism activity as a function of age which can be characterized via least squares regression where the slope of age vs. (AAMU+1MX+1MU)/1,7U ratio is examined for deviations from zero.

Outcome measures

Outcome measures
Measure	Longitudinal Assessment Cohort n=111 Participants Normal healthy children approximately one year of age followed through five years of age to evaluate the ontogeny of CYP1A2, CYP2D6, CYP3A4.
Change in CYP1A2 Drug Metabolism Phenotype With Age Log ((AAMU+1MX+1MU)/1,7U) Milestone 2	-0.823 unitless ratio Standard Deviation 0.170
Change in CYP1A2 Drug Metabolism Phenotype With Age Log ((AAMU+1MX+1MU)/1,7U) Milestone 1	-0.851 unitless ratio Standard Deviation 0.185
Change in CYP1A2 Drug Metabolism Phenotype With Age Log ((AAMU+1MX+1MU)/1,7U) Milestone 3	-0.858 unitless ratio Standard Deviation 0.204
Change in CYP1A2 Drug Metabolism Phenotype With Age Log ((AAMU+1MX+1MU)/1,7U) Milestone 4	-0.856 unitless ratio Standard Deviation 0.150
Change in CYP1A2 Drug Metabolism Phenotype With Age Log ((AAMU+1MX+1MU)/1,7U) Milestone 5	-0.832 unitless ratio Standard Deviation 0.168
Change in CYP1A2 Drug Metabolism Phenotype With Age Log ((AAMU+1MX+1MU)/1,7U) Milestone 6	-0.853 unitless ratio Standard Deviation 0.169
Change in CYP1A2 Drug Metabolism Phenotype With Age Log ((AAMU+1MX+1MU)/1,7U) Milestone 7	-0.822 unitless ratio Standard Deviation 0.142
Change in CYP1A2 Drug Metabolism Phenotype With Age Log ((AAMU+1MX+1MU)/1,7U) Milestone 8	-0.851 unitless ratio Standard Deviation 0.170
Change in CYP1A2 Drug Metabolism Phenotype With Age Log ((AAMU+1MX+1MU)/1,7U) Milestone 9	-0.821 unitless ratio Standard Deviation 0.167

Adverse Events

Longitudinal Assessment Cohort

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

J. Steven Leeder

Children's Mercy Hospital

Phone: 816-234-3059

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place