Trial Outcomes & Findings for CYP2B6 Polymorphisms in Methadone Disposition (NCT NCT01648283)

NCT ID: NCT01648283

Last Updated: 2018-06-20

Results Overview

Plasma metabolite EDDP/methadone area under the concentration-time curve (AUC0-96) ratio

Recruitment status

COMPLETED

Study phase

NA

Target enrollment

78 participants

Primary outcome timeframe

up to 96 hours

Results posted on

2018-06-20

Participant Flow

11 subject withdrawals following consent due to personal reasons and/or conflicts, 3 subjects not evaluable, 64 subjects evaluable and included in analysis

Participant milestones

Participant milestones
Measure
Methadone Arm
1. Intravenous racemic methadone HCl, 6.0 mg bolus 2. Oral deuterated racemic methadone HCl, 11 mg capsule (IND#58,511) CYP2B6 is phenotyped by the clearance oral racemic bupropion 150mg racemic methadone HC1: IV racemic Methadone HC1 6 mg oral d5-methadon HC1 11 mg Oral deuterated racemic methadone HCl,: 11 mg capsule once
Overall Study
STARTED
78
Overall Study
COMPLETED
64
Overall Study
NOT COMPLETED
14

Reasons for withdrawal

Reasons for withdrawal
Measure
Methadone Arm
1. Intravenous racemic methadone HCl, 6.0 mg bolus 2. Oral deuterated racemic methadone HCl, 11 mg capsule (IND#58,511) CYP2B6 is phenotyped by the clearance oral racemic bupropion 150mg racemic methadone HC1: IV racemic Methadone HC1 6 mg oral d5-methadon HC1 11 mg Oral deuterated racemic methadone HCl,: 11 mg capsule once
Overall Study
Withdrawal by Subject
14

Baseline Characteristics

CYP2B6 Polymorphisms in Methadone Disposition

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Methadone Arm
n=64 Participants
1. Intravenous racemic methadone HCl, 6.0 mg bolus 2. Oral deuterated racemic methadone HCl, 11 mg capsule (IND#58,511) CYP2B6 is phenotyped by the clearance oral racemic bupropion 150mg racemic methadone HC1: IV racemic Methadone HC1 6 mg oral d5-methadon HC1 11 mg Oral deuterated racemic methadone HCl,: 11 mg capsule once
Age, Categorical
<=18 years
0 Participants
n=5 Participants
Age, Categorical
Between 18 and 65 years
64 Participants
n=5 Participants
Age, Categorical
>=65 years
0 Participants
n=5 Participants
Sex: Female, Male
Female
34 Participants
n=5 Participants
Sex: Female, Male
Male
30 Participants
n=5 Participants
Ethnicity (NIH/OMB)
Hispanic or Latino
1 Participants
n=5 Participants
Ethnicity (NIH/OMB)
Not Hispanic or Latino
63 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
10 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
10 Participants
n=5 Participants
Race (NIH/OMB)
White
42 Participants
n=5 Participants
Race (NIH/OMB)
More than one race
0 Participants
n=5 Participants
Race (NIH/OMB)
Unknown or Not Reported
2 Participants
n=5 Participants
Region of Enrollment
United States
64 participants
n=5 Participants

PRIMARY outcome

Timeframe: up to 96 hours

Population: Plasma EDDP/methadone AUC ratio

Plasma metabolite EDDP/methadone area under the concentration-time curve (AUC0-96) ratio

Outcome measures

Outcome measures
Measure
CYP2B6*1/*1
n=21 Participants
Oral R-methadone HCl
CYP2B6*1/*6
n=20 Participants
Oral R-methadone
CYP2B6*6/*6
n=17 Participants
Oral R-methadone
Methadone Metabolism
0.082 ratio
Standard Deviation 0.022
0.073 ratio
Standard Deviation 0.026
0.054 ratio
Standard Deviation 0.017

Adverse Events

Methadone Arm

Serious events: 0 serious events
Other events: 56 other events
Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure
Methadone Arm
n=67 participants at risk
1. Intravenous racemic methadone HCl, 6.0 mg bolus 2. Oral deuterated racemic methadone HCl, 11 mg capsule (IND#58,511) CYP2B6 is phenotyped by the clearance oral racemic bupropion 150mg racemic methadone HC1: IV racemic Methadone HC1 6 mg oral d5-methadon HC1 11 mg Oral deuterated racemic methadone HCl,: 11 mg capsule once
Gastrointestinal disorders
Nausea
62.7%
42/67 • Number of events 42
General disorders
Headache
22.4%
15/67 • Number of events 15
Skin and subcutaneous tissue disorders
Itching
38.8%
26/67 • Number of events 26
General disorders
Dizzyness
38.8%
26/67 • Number of events 26
General disorders
syncope
1.5%
1/67 • Number of events 1
General disorders
feeling "hyperactive"
1.5%
1/67 • Number of events 1
General disorders
light senstivity
1.5%
1/67

Additional Information

Evan D. Kharasch, MD, PhD

Washington University School of Medicine

Phone: 314-362-8796

Results disclosure agreements

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