CYP2B6 Polymorphisms in Ketamine

• Sponsor: Washington University School of Medicine (Other)
• Overall Status: Completed
• CT.gov ID: NCT01988922
• Collaborator: (none)
• Enrollment: 30
• Location: 1
• Arms: 3
• Duration (Months): 42
• Patients Per Site Per Month: 0.7

Study Details

Study Description

Brief Summary

This research study will determine if genetic variation in CYP2B6 affects how the body metabolizes ketamine.

Condition or Disease	Intervention/Treatment	Phase
Healthy Volunteers	Drug: ketamine	N/A

Study Design

• Study Type: Interventional
• Actual Enrollment: 30 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Other
• Official Title: Role of CYP2B6 Polymorphisms in Ketamine Metabolism and Clearance
• Study Start Date: Nov 1, 2013
• Actual Primary Completion Date: May 1, 2016
• Actual Study Completion Date: May 1, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Ketamine arm- *1/*1 1.*1/*1- oral racemic ketamine 0.4 mg/kg	Drug: ketamine; 0.4 mg/kg oral racemic ketamine
Experimental: Ketamine arm - *1/*6 2. *1/*6- oral racemic ketamine 0.4 mg/kg	Drug: ketamine; 0.4 mg/kg oral racemic ketamine
Experimental: Ketamine arm - *6/*6 3. *6/*6- oral racemic ketamine 0.4 mg/kg	Drug: ketamine; 0.4 mg/kg oral racemic ketamine

Outcome Measures

Primary Outcome Measures

1. The Effects of CYP2B6 Genetic Variants on Ketamine Metabolism and Clearance by CYP2B6*6 Hetero or Homozygote Genotype. [up to 24 hours]

   Ketamine metabolism, measured as the plasma norketamine/ketamine AUC ratio in CYP2B6*6 carriers (CYP2B6*6 hetero or homozygotes) compared to the wild-type CYP2B6*1/*1 genotype Ketamine, norketamine, and dehydronorketamine concentrations in plasma and urine were determined by enantioselective HPLC tandem mass spectrometry, using solid phase extraction, based on a modification of a published method.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 50 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

1. 18-50 yr old

2. CYP2B6*1/1, CYP2B61/6 or CYP2B66/*6 genotype (see table) (Note: subjects of other rare genotype but with one or more 516G>T, 785A>G, 983T>C or 1459C>T polymorphism may be enrolled at PI's discretion)

3. Good general health with no remarkable medical conditions

4. BMI <33

5. Provided informed consent

Exclusion Criteria:

1. Known history of liver or kidney disease

2. Use of prescription or non prescription medications, herbals, foods or chemicals known to be metabolized by or affecting CYP2B6

3. Females who are pregnant or nursing

4. Known history of drug or alcohol addiction (prior or present addiction or treatment for addiction)

5. Direct physical access to and routine handling of addicting drugs in the regular course of duty (this is a routine exclusion from studies of drugs with addiction potential)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Washington University School of Medicine	Saint Louis	Missouri	United States	63110

Sponsors and Collaborators

• Washington University School of Medicine

Investigators

• Principal Investigator: Lesley Rao, MD, Washington University School of Medicine

Study Documents (Full-Text)

• Study Protocol - Jul 9, 2013
• Statistical Analysis Plan - Jul 9, 2013

More Information

Publications

None provided.

• Responsible Party: Washington University School of Medicine
• ClinicalTrials.gov Identifier: NCT01988922
• Other Study ID Numbers: 201307034
• First Posted: Nov 20, 2013
• Last Update Posted: May 18, 2018
• Last Verified: Apr 1, 2018

• Keywords provided by Washington University School of Medicine: ketamine polymorphisms
• Additional relevant MeSH terms: Ketamine

Study Results

Participant Flow

Arm/Group Title	Ketamine Arm- *1/*1	Ketamine Arm - *1/*6	Ketamine Arm - *6/*6
Arm/Group Description	1.*1/*1- oral racemic ketamine 0.4 mg/kg ketamine: 0.4 mg/kg oral racemic ketamine as a one-time dose	2. *1/*6- oral racemic ketamine 0.4 mg/kg ketamine: 0.4 mg/kg oral racemic ketamine as a one-time dose	3. *6/*6- oral racemic ketamine 0.4 mg/kg ketamine: 0.4 mg/kg oral racemic ketamine as a one-time dose
Period Title: Overall Study
STARTED	10	10	10
COMPLETED	10	10	10
NOT COMPLETED	0	0	0

Baseline Characteristics

Arm/Group Title	Ketamine Arm- *1/*1	Ketamine Arm - *1/*6	Ketamine Arm - *6/*6	Total
Arm/Group Description	1.*1/*1- oral racemic ketamine 0.4 mg/kg ketamine: 0.4 mg/kg oral racemic ketamine	2. *1/*6- oral racemic ketamine 0.4 mg/kg ketamine: 0.4 mg/kg oral racemic ketamine	3. *6/*6- oral racemic ketamine 0.4 mg/kg ketamine: 0.4 mg/kg oral racemic ketamine	Total of all reporting groups
Overall Participants	10	10	10	30
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	10 100%	10 100%	10 100%	30 100%
>=65 years	0 0%	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	25 (6)	27 (11)	37 (13)	29 (10)
Sex: Female, Male (Count of Participants)
Female	3 30%	4 40%	4 40%	11 36.7%
Male	7 70%	6 60%	6 60%	19 63.3%
Region of Enrollment (participants) [Number]
United States	10 100%	10 100%	10 100%	10 33.3%

Outcome Measures

1. Primary Outcome

Title	The Effects of CYP2B6 Genetic Variants on Ketamine Metabolism and Clearance by CYP2B6*6 Hetero or Homozygote Genotype.
Description	Ketamine metabolism, measured as the plasma norketamine/ketamine AUC ratio in CYP2B6*6 carriers (CYP2B6*6 hetero or homozygotes) compared to the wild-type CYP2B6*1/*1 genotype Ketamine, norketamine, and dehydronorketamine concentrations in plasma and urine were determined by enantioselective HPLC tandem mass spectrometry, using solid phase extraction, based on a modification of a published method.
Time Frame	up to 24 hours

Outcome Measure Data

Analysis Population Description

3 genotype groups, metabolism measured for both R- and S-ketamine

Arm/Group Title	R-ketamine *1/*1	S-ketamine *1/*1	R-ketamine *1/*6	S-ketamine *1/*6	R-ketamine *6/*6	S-ketamine *6/*6
Arm/Group Description
Measure Participants	10	10	10	10	10	10
Mean (Standard Deviation) [ng/ml*hr]	29 (10)	21 (7)	26 (11)	19 (10)	35 (21)	23 (13)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	R-ketamine *1/*1, S-ketamine *1/*1, R-ketamine *1/*6, S-ketamine *1/*6, R-ketamine *6/*6, S-ketamine *6/*6
	Comments
	Type of Statistical Test	Other
	Comments	Differences between CYP2B6*1/*1, CYP2B6*1/*6, and CYP2B6*6/*6 genotypes for pharmacokinetic parameters were analyzed using one-way ANOVA followed by the Student-Newman-Keuls test for multiple comparisons (Sigmaplot 12.5; Systat Software, Inc, USA). Nonnormal data were log transformed for analysis but reported as the nontransformed results.
Statistical Test of Hypothesis	p-Value	<0.05
	Comments
	Method	ANOVA
	Comments	One-way ANOVA followed by the Student-Newman-Keuls test for multiple comparisons

Adverse Events

Arm/Group Title	Ketamine Arm- *1/*1		Ketamine Arm - *1/*6		Ketamine Arm - *6/*6
Arm/Group Description	1.*1/*1- oral racemic ketamine 0.4 mg/kg ketamine: 0.4 mg/kg oral racemic ketamine		2. *1/*6- oral racemic ketamine 0.4 mg/kg ketamine: 0.4 mg/kg oral racemic ketamine		3. *6/*6- oral racemic ketamine 0.4 mg/kg ketamine: 0.4 mg/kg oral racemic ketamine
All Cause Mortality
	Ketamine Arm- *1/*1		Ketamine Arm - *1/*6		Ketamine Arm - *6/*6
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Ketamine Arm- *1/*1		Ketamine Arm - *1/*6		Ketamine Arm - *6/*6
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/10 (0%)		0/10 (0%)		0/10 (0%)
Other (Not Including Serious) Adverse Events
	Ketamine Arm- *1/*1		Ketamine Arm - *1/*6		Ketamine Arm - *6/*6
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/10 (0%)		0/10 (0%)		0/10 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.