Trial Outcomes & Findings for CYP2B6 Genetics and Drug Interactions in Healthy Volunteers (NCT NCT02401256)
NCT ID: NCT02401256
Last Updated: 2017-10-11
Results Overview
After the samples collection, blood from phase 2 and phase 4 were used to perform the quantification of Efavirenz in plasma. The composite of the efavirenz concentration (blood collection between 0 to 120 hrs) were used to calculate the area under the plasma concentration time curve (AUC0-inf for single dose and AUC0-24 for multiple dose) of efavirenz.
Recruitment status
COMPLETED
Study phase
PHASE4
Target enrollment
70 participants
Primary outcome timeframe
Single dose pharmacokinetics (PK) versus multiple doses (after 17 day pretreatment) PK (total 38 days for each subject)
Results posted on
2017-10-11
Participant Flow
A total of 70 volunteers were enrolled study, 53 completed the whole study and 17 subjects withdraw from the study (6 during Phase 1, 6 during Phase 2 and 5 during Phase 3). We did include on the data analysis 8 volunteers that withdraw from the study but had Efavirenz quantification information and CYP2B6 genotypes (Analysed volunteers = 61)
Participant milestones
| Measure |
CYP2B6
A cocktail of bupropion (100mg), montelukast (10mg) and rosuvastatin (5mg). These drugs will be administrated on 3 occasions (at the begging each inpatient visit of Phase 1, 2 and 4). The study has 4 phases: Phase 1 (control, baseline)Subjects received simultaneously a cocktail of a single dose of bupropion 100 mg (CYP2b6), montelukast 10 mg (CYP2C8) and rosuvastatin 5 mg (OATP1B1/BCRP) by mouth and their metabolism and pharmacokinetics determined. Phase 2 (inhibition)a single 600 mg oral dose of efavirenz is administered with the cocktail drugs listed above and their metabolism and pharmacokinetics determined Phase 3 (home treatment with efavirenz): Subjects is taken take efavirenz for approximately 17 days Phase 4 (induction): as in phase 2. Blood samples (0 to 120 hrs) and urine voided over 48 hrs (Phases 1, 2 and 4) are collected in all phases. Blood draws is made in phase 3 for trough concentration measurements.
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|---|---|
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Overall Study
STARTED
|
70
|
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Overall Study
Finished Phase 1
|
64
|
|
Overall Study
Finished Phase 2
|
58
|
|
Overall Study
Finished Phase 3
|
53
|
|
Overall Study
Analysed
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61
|
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Overall Study
COMPLETED
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53
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Overall Study
NOT COMPLETED
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17
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Reasons for withdrawal
| Measure |
CYP2B6
A cocktail of bupropion (100mg), montelukast (10mg) and rosuvastatin (5mg). These drugs will be administrated on 3 occasions (at the begging each inpatient visit of Phase 1, 2 and 4). The study has 4 phases: Phase 1 (control, baseline)Subjects received simultaneously a cocktail of a single dose of bupropion 100 mg (CYP2b6), montelukast 10 mg (CYP2C8) and rosuvastatin 5 mg (OATP1B1/BCRP) by mouth and their metabolism and pharmacokinetics determined. Phase 2 (inhibition)a single 600 mg oral dose of efavirenz is administered with the cocktail drugs listed above and their metabolism and pharmacokinetics determined Phase 3 (home treatment with efavirenz): Subjects is taken take efavirenz for approximately 17 days Phase 4 (induction): as in phase 2. Blood samples (0 to 120 hrs) and urine voided over 48 hrs (Phases 1, 2 and 4) are collected in all phases. Blood draws is made in phase 3 for trough concentration measurements.
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|---|---|
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Overall Study
Adverse Event
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5
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Overall Study
Withdrawal by Subject
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12
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Baseline Characteristics
CYP2B6 Genetics and Drug Interactions in Healthy Volunteers
Baseline characteristics by cohort
| Measure |
CYP2B6
n=70 Participants
A cocktail of bupropion (100mg), montelukast (10mg) and rosuvastatin (5mg). These drugs will be administrated on 3 occasions (at the begging each inpatient visit of Phase 1, 2 and 4). The study has 4 phases: Phase 1 (control, baseline)Subjects received simultaneously a cocktail of a single dose of bupropion 100 mg (CYP2b6), montelukast 10 mg (CYP2C8) and rosuvastatin 5 mg (OATP1B1/BCRP) by mouth and their metabolism and pharmacokinetics determined. Phase 2 (inhibition)a single 600 mg oral dose of efavirenz is administered with the cocktail drugs listed above and their metabolism and pharmacokinetics determined Phase 3 (home treatment with efavirenz): Subjects is taken take efavirenz for approximately 17 days Phase 4 (induction): as in phase 2. Blood samples (0 to 120 hrs) and urine voided over 48 hrs (Phases 1, 2 and 4) are collected in all phases. Blood draws is made in phase 3 for trough concentration measurements.
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|---|---|
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Age, Continuous
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25.5 years
STANDARD_DEVIATION 6.9 • n=93 Participants
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Sex: Female, Male
Female
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31 Participants
n=93 Participants
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Sex: Female, Male
Male
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39 Participants
n=93 Participants
|
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Ethnicity (NIH/OMB)
Hispanic or Latino
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8 Participants
n=93 Participants
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Ethnicity (NIH/OMB)
Not Hispanic or Latino
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62 Participants
n=93 Participants
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Ethnicity (NIH/OMB)
Unknown or Not Reported
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0 Participants
n=93 Participants
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Race (NIH/OMB)
American Indian or Alaska Native
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0 Participants
n=93 Participants
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|
Race (NIH/OMB)
Asian
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14 Participants
n=93 Participants
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|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
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0 Participants
n=93 Participants
|
|
Race (NIH/OMB)
Black or African American
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12 Participants
n=93 Participants
|
|
Race (NIH/OMB)
White
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40 Participants
n=93 Participants
|
|
Race (NIH/OMB)
More than one race
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4 Participants
n=93 Participants
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|
Race (NIH/OMB)
Unknown or Not Reported
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0 Participants
n=93 Participants
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PRIMARY outcome
Timeframe: Single dose pharmacokinetics (PK) versus multiple doses (after 17 day pretreatment) PK (total 38 days for each subject)Population: Just volunteers with Efavirenz quantification information (complete or partial) and CYP2B6 genotype were included in this data analysis (Total of 61)
After the samples collection, blood from phase 2 and phase 4 were used to perform the quantification of Efavirenz in plasma. The composite of the efavirenz concentration (blood collection between 0 to 120 hrs) were used to calculate the area under the plasma concentration time curve (AUC0-inf for single dose and AUC0-24 for multiple dose) of efavirenz.
Outcome measures
| Measure |
CYP2B6*1/*1
n=22 Participants
A cocktail of bupropion (100mg), montelukast (10mg) and rosuvastatin (5mg).These drugs will be administrated on 3 occasions (at the begging each inpatient visit of Phase 1, 2 and 4).The study has 4 phases:Phase 1(control/baseline).Subjects received simultaneously a cocktail of a single dose of bupropion 100 mg(CYP2B6), montelukast 10 mg(CYP2C8) and rosuvastatin 5 mg(OATP1B1/BCRP) by mouth and their metabolism and pharmacokinetics determined.Phase 2(inhibition)a single 600 mg oral dose of efavirenz is administered with the cocktail drugs listed above and their metabolism and pharmacokinetics determined Phase 3(home treatment with efavirenz):Subjects take efavirenz for approximately 17 days Phase 4 (induction): as in phase 2.Blood samples (0 to 120 hrs) and urine voided over 48 hrs(Phases 1, 2 and 4) are collected in all phases.Blood draws is made in phase 3 for trough concentration measurements. Volunteers were genotyped and stratified according to CYP2B6\*1/\*1, \*1/\*6, and \*6/\*6 alleles
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CYP2B6*1/*6
n=33 Participants
A cocktail of bupropion (100mg), montelukast (10mg) and rosuvastatin (5mg).These drugs will be administrated on 3 occasions (at the begging each inpatient visit of Phase 1, 2 and 4).The study has 4 phases:Phase 1(control/baseline).Subjects received simultaneously a cocktail of a single dose of bupropion 100 mg(CYP2B6), montelukast 10 mg(CYP2C8) and rosuvastatin 5 mg(OATP1B1/BCRP) by mouth and their metabolism and pharmacokinetics determined.Phase 2(inhibition)a single 600 mg oral dose of efavirenz is administered with the cocktail drugs listed above and their metabolism and pharmacokinetics determined Phase 3(home treatment with efavirenz):Subjects take efavirenz for approximately 17 days Phase 4 (induction): as in phase 2.Blood samples (0 to 120 hrs) and urine voided over 48 hrs(Phases 1, 2 and 4) are collected in all phases.Blood draws is made in phase 3 for trough concentration measurements. Volunteers were genotyped and stratified according to CYP2B6\*1/\*1, \*1/\*6, and \*6/\*6 alleles
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CYP2B6*6/*6
n=6 Participants
A cocktail of bupropion (100mg), montelukast (10mg) and rosuvastatin (5mg).These drugs will be administrated on 3 occasions (at the begging each inpatient visit of Phase 1, 2 and 4).The study has 4 phases:Phase 1(control/baseline).Subjects received simultaneously a cocktail of a single dose of bupropion 100 mg(CYP2B6), montelukast 10 mg(CYP2C8) and rosuvastatin 5 mg(OATP1B1/BCRP) by mouth and their metabolism and pharmacokinetics determined.Phase 2(inhibition)a single 600 mg oral dose of efavirenz is administered with the cocktail drugs listed above and their metabolism and pharmacokinetics determined Phase 3(home treatment with efavirenz):Subjects take efavirenz for approximately 17 days Phase 4 (induction): as in phase 2.Blood samples (0 to 120 hrs) and urine voided over 48 hrs(Phases 1, 2 and 4) are collected in all phases.Blood draws is made in phase 3 for trough concentration measurements. Volunteers were genotyped and stratified according to CYP2B6\*1/\*1, \*1/\*6, and \*6/\*6 alleles
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|---|---|---|---|
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Efavirenz AUC0-inf (Single Dose) and AUC0-24(Multiple Dose)
Efavirenz AUC0-inf (Single Dose)
|
411.53 h*uM
Standard Deviation 144.00
|
620.36 h*uM
Standard Deviation 269.12
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522.42 h*uM
Standard Deviation 31.40
|
|
Efavirenz AUC0-inf (Single Dose) and AUC0-24(Multiple Dose)
Efavirenz AUC0-24 (Multiple Dose)
|
183.97 h*uM
Standard Deviation 62.49
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254.40 h*uM
Standard Deviation 65.59
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321.86 h*uM
Standard Deviation 146.28
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Adverse Events
CYP2B6
Serious events: 0 serious events
Other events: 5 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
CYP2B6
n=70 participants at risk
A cocktail of bupropion (100mg), montelukast (10mg) and rosuvastatin (5mg). These drugs will be administrated on 3 occasions (at the begging each inpatient visit of Phase 1, 2 and 4). The study has 4 phases: Phase 1 (control, baseline)Subjects received simultaneously a cocktail of a single dose of bupropion 100 mg (CYP2b6), montelukast 10 mg (CYP2C8) and rosuvastatin 5 mg (OATP1B1/BCRP) by mouth and their metabolism and pharmacokinetics determined. Phase 2 (inhibition)a single 600 mg oral dose of efavirenz is administered with the cocktail drugs listed above and their metabolism and pharmacokinetics determined Phase 3 (home treatment with efavirenz): Subjects is taken take efavirenz for approximately 17 days Phase 4 (induction): as in phase 2. Blood samples (0 to 120 hrs) and urine voided over 48 hrs (Phases 1, 2 and 4) are collected in all phases. Blood draws is made in phase 3 for trough concentration measurements.
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|---|---|
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General disorders
Efavirenz side effects
|
7.1%
5/70 • Number of events 5
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Additional Information
Dr. Zeruesenay Desta
Indiana University School of Medicine
Phone: 3172742823
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place