Back to resultsA Study to Evaluate the Pharmacokinetic Effect of SCH 503034 (Boceprevir) on Methadone or Buprenorphine/Naloxone Plasma Concentrations (P08123)
Primary Purpose
Hepatitis C Virus
Status
Completed
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
boceprevir
methadone
buprenorphine/naloxone
Sponsored by
About this trial
This is an interventional treatment trial for Hepatitis C Virus
Eligibility Criteria
Inclusion Criteria:
- Body Mass Index (BMI) between 18 and 36, inclusive
- Reliable participation in a methadone maintenance or buprenorphine maintenance or buprenorphine/naloxone maintenance program for at least two (2) months prior to Day 1.
- Is receiving once daily oral dose of methadone therapy at a stable
individualized dose for at least 4 weeks, receiving once
daily buprenorphine dose at a stable individualized dose for at 4 weeks with, if on buprenorphine only therapy, naloxone added for at least 2 weeks prior to Day 1.
- 12-lead electrocardiogram (ECG) conduction intervals within gender-specific normal range
- Vital signs within normal range
- Clinical laboratory tests within normal range
- Women who are postmenopausal, surgically sterilized, or premenopausal and use a medically-accepted method of contraception.
Exclusion Criteria:
- Pregnancy, breast feeding, or intention to become pregnant or father a child while on study or within 3 months after end of trial
- History or presence of inflammatory bowel disease, ulcers, or gastrointestinal or rectal bleeding
- History of major gastrointestinal tract surgery such as gastrectomy, gastroenterostomy, or bowel resection
- History of pancreatic injury or pancreatitis
- History or presence of liver disease or liver injury
- History or presence of impaired renal function
- History of urinary obstruction or difficulty in voiding
- History of any infectious disease within 4 weeks prior to drug administration that in the opinion of the investigator, affects the subject's ability to participate in the trial
- Positive for hepatitis B surface antigen, hepatitis C antibodies or human immunodeficiency virus (HIV)
- Positive screen for drugs with a high potential for abuse such as cocaine, amphetamines, methylenedioxymethamphetamine (MDMA), barbiturates, benzodiazepines, or opiates/opioids
Excessive use of alcohol in the 2 weeks prior to Day -1, defined as greater than 3 glasses of alcoholic beverages (1 is approximately equivalent to: beer [284 mL/10 oz], wine
[125 mL/4 oz], or distilled spirits [25 mL/1 oz]) per day.
- Blood donation in the past 60 days
- Previous administration of SCH 503034 (boceprevir)
- Current participation in another clinical study or participation in a clinical study (e.g., laboratory or clinical evaluation) within 30 days of baseline
- Study staff personnel or family members of the study staff personnel
- Demonstrated allergic reactions (eg, food, drug, atopic reactions or asthmatic episodes) that, in the opinion of the investigator and sponsor, interfere with their ability to participate in the trial
- History of malignancy within 5 years from Screening
- Consumption of excessive amounts (equivalent to > 6 cups of brewed coffee/day) of coffee, tea, cola or other caffeinated beverages
- Receipt of any of the following more recently than the washout period prior to Baseline: inhibitors or inducers of cytochrome (CYP) P450, CYP2B6, CYP3A4, and CYP2D6; or oral contraceptives containing drospirenone
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Methadone + boceprevir
Buprenorphine/naloxone + boceprevir
Arm Description
Participants receive standard methadone maintenance therapy (20-150 mg tablets, liquid, or disket, orally, once per day) on Days 1 through 8 + boceprevir (800 mg [4 x 200 mg capsules], orally, every 8 hours) on Days 2 through 7)
Participants receive standard buprenorphine/naloxone maintenance therapy (8/2-24/6 mg, tablets, sublingual, once per day) on Days 1 through 8 + boceprevir (800 mg [4 x 200 mg capsules], orally, every 8 hours) on Days 2 through 7
Outcomes
Primary Outcome Measures
Area Under the Concentration Versus Time Curve (AUC) at Steady State of Methadone Enantiomers When Administered With or Without Boceprevir
AUC is a measure of the amount of drug in the blood over time, measured at steady state (time at which the amount of drug eliminated by the body is in equilibrium with the amount taken in). The Day 1, 0 through 24 hour samples were for methadone levels in the absence of boceprevir co-administration. The Day 7, 0 through 24 hour samples were for methadone levels in the presence of boceprevir co-administration. The Day 5 and 6 predose samples were to check steady state for methadone + boceprevir.
Maximum Concentration (Cmax) at Steady State of Methadone Enantiomers When Administered With or Without Boceprevir
Cmax is a measure of the maximum level of drug in the blood, measured at steady state (time at which the amount of drug eliminated by the body is in equilibrium with the amount taken in). The Day 1, 0 through 24 hour samples were for methadone levels in the absence of boceprevir co-administration. The Day 7, 0 through 24 hour samples were for methadone levels in the presence of boceprevir co-administration. The Day 5 and 6 predose samples were to check steady state for methadone + boceprevir.
AUC of Buprenorphine (Administered in Combination With Naloxone) at Steady State With or Without Boceprevir
AUC is a measure of the amount of drug in the blood over time, measured at steady state (time at which the amount of drug eliminated by the body is in equilibrium with the amount taken in). The Day 1, 0 through 24 hour samples were for buprenorphine/naloxone levels in the absence of boceprevir co-administration. The Day 7, 0 through 24 hour samples were for buprenorphine/naloxone levels in the presence of boceprevir co-administration. The Day 5 and 6 predose samples were to check steady state for buprenorphine/naloxone + boceprevir.
Cmax of Buprenorphine (Administered in Combination With Naloxone) at Steady State With or Without Boceprevir
Cmax is a measure of the maximum level of drug in the blood, measured at steady state (time at which the amount of drug eliminated by the body is in equilibrium with the amount taken in). The Day 1, 0 through 24 hour samples were for buprenorphine/naloxone levels in the absence of boceprevir co-administration. The Day 7, 0 through 24 hour samples were for buprenorphine/naloxone levels in the presence of boceprevir co-administration. The Day 5 and 6 predose samples were to check steady state for buprenorphine/naloxone + boceprevir.
Secondary Outcome Measures
AUC of Naloxone (Administered in Combination With Buprenorphine) at Steady State With or Without Boceprevir
AUC is a measure of the amount of drug in the blood over time, measured at steady state (time at which the amount of drug eliminated by the body is in equilibrium with the amount taken in). The Day 1, 0 through 24 hour samples were for buprenorphine/naloxone levels in the absence of boceprevir co-administration. The Day 7, 0 through 24 hour samples were for buprenorphine/naloxone levels in the presence of boceprevir co-administration. The Day 5 and 6 predose samples were to check steady state for buprenorphine/naloxone + boceprevir.
Cmax of Naloxone (Administered in Combination With Buprenorphine) at Steady State With or Without Boceprevir
Cmax is a measure of the maximum level of drug in the blood, measured at steady state (time at which the amount of drug eliminated by the body is in equilibrium with the amount taken in). The Day 1, 0 through 24 hour samples were for buprenorphine/naloxone levels in the absence of boceprevir co-administration. The Day 7, 0 through 24 hour samples were for buprenorphine/naloxone levels in the presence of boceprevir co-administration. The Day 5 and 6 predose samples were to check steady state for buprenorphine/naloxone + boceprevir.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01396005
Brief Title
A Study to Evaluate the Pharmacokinetic Effect of SCH 503034 (Boceprevir) on Methadone or Buprenorphine/Naloxone Plasma Concentrations (P08123)
Official Title
An Open-Label, One-Period Study in Patients Receiving Methadone or Buprenorphine/Naloxone Maintenance Therapy to Evaluate the Effect of SCH 503034 (Boceprevir) on Either Methadone or Buprenorphine/Naloxone Plasma Concentrations (Protocol No. P08123)
Study Type
Interventional
2. Study Status
Record Verification Date
March 2017
Overall Recruitment Status
Completed
Study Start Date
September 2011 (undefined)
Primary Completion Date
December 2011 (Actual)
Study Completion Date
December 2011 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Merck Sharp & Dohme LLC
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
In this study, participants on methadone or buprenorphine/naloxone maintenance therapy will be given boceprevir. Blood samples will be taken at specified intervals to find out whether boceprevir affects the pharmacokinetics of methadone, buprenorphine, or naloxone.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hepatitis C Virus
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
21 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Methadone + boceprevir
Arm Type
Experimental
Arm Description
Participants receive standard methadone maintenance therapy (20-150 mg tablets, liquid, or disket, orally, once per day) on Days 1 through 8 + boceprevir (800 mg [4 x 200 mg capsules], orally, every 8 hours) on Days 2 through 7)
Arm Title
Buprenorphine/naloxone + boceprevir
Arm Type
Experimental
Arm Description
Participants receive standard buprenorphine/naloxone maintenance therapy (8/2-24/6 mg, tablets, sublingual, once per day) on Days 1 through 8 + boceprevir (800 mg [4 x 200 mg capsules], orally, every 8 hours) on Days 2 through 7
Intervention Type
Drug
Intervention Name(s)
boceprevir
Other Intervention Name(s)
SCH 503034, Victrelis™
Intervention Description
boceprevir 800 mg (4 x 200 mg capsules), orally, every 8 hours, Day 2 through Day 7
Intervention Type
Drug
Intervention Name(s)
methadone
Intervention Description
methadone, 20-150 mg tablets, liquid, or disket, orally, once per day, Day 1 through Day 8
Intervention Type
Drug
Intervention Name(s)
buprenorphine/naloxone
Intervention Description
buprenorphine/naloxone 8/2-24/6 mg, tablets, sublingual, once per day, Day 1 through Day 8
Primary Outcome Measure Information:
Title
Area Under the Concentration Versus Time Curve (AUC) at Steady State of Methadone Enantiomers When Administered With or Without Boceprevir
Description
AUC is a measure of the amount of drug in the blood over time, measured at steady state (time at which the amount of drug eliminated by the body is in equilibrium with the amount taken in). The Day 1, 0 through 24 hour samples were for methadone levels in the absence of boceprevir co-administration. The Day 7, 0 through 24 hour samples were for methadone levels in the presence of boceprevir co-administration. The Day 5 and 6 predose samples were to check steady state for methadone + boceprevir.
Time Frame
Methadone samples collected Day 1, 0 (predose) through 24 hours post-dose (Day 2). Boceprevir and methadone samples collected Day 7, 0 (predose) through 24 hours post-dose (Day 8). Predose samples also collected on Days 5-6.
Title
Maximum Concentration (Cmax) at Steady State of Methadone Enantiomers When Administered With or Without Boceprevir
Description
Cmax is a measure of the maximum level of drug in the blood, measured at steady state (time at which the amount of drug eliminated by the body is in equilibrium with the amount taken in). The Day 1, 0 through 24 hour samples were for methadone levels in the absence of boceprevir co-administration. The Day 7, 0 through 24 hour samples were for methadone levels in the presence of boceprevir co-administration. The Day 5 and 6 predose samples were to check steady state for methadone + boceprevir.
Time Frame
Methadone samples collected Day 1, 0 (predose) through 24 hours post-dose (Day 2). Boceprevir and methadone samples collected Day 7, 0 (predose) through 24 hours post-dose (Day 8). Predose samples also collected on Days 5-6.
Title
AUC of Buprenorphine (Administered in Combination With Naloxone) at Steady State With or Without Boceprevir
Description
AUC is a measure of the amount of drug in the blood over time, measured at steady state (time at which the amount of drug eliminated by the body is in equilibrium with the amount taken in). The Day 1, 0 through 24 hour samples were for buprenorphine/naloxone levels in the absence of boceprevir co-administration. The Day 7, 0 through 24 hour samples were for buprenorphine/naloxone levels in the presence of boceprevir co-administration. The Day 5 and 6 predose samples were to check steady state for buprenorphine/naloxone + boceprevir.
Time Frame
Buprenorphine/naloxone samples collected Day 1, 0 (predose) through 24 hours post-dose (Day 2). Boceprevir and buprenorphine/naloxone samples collected Day 7, 0 (predose) through 24 hours post-dose (Day 8). Predose samples also collected on Days 5-6.
Title
Cmax of Buprenorphine (Administered in Combination With Naloxone) at Steady State With or Without Boceprevir
Description
Cmax is a measure of the maximum level of drug in the blood, measured at steady state (time at which the amount of drug eliminated by the body is in equilibrium with the amount taken in). The Day 1, 0 through 24 hour samples were for buprenorphine/naloxone levels in the absence of boceprevir co-administration. The Day 7, 0 through 24 hour samples were for buprenorphine/naloxone levels in the presence of boceprevir co-administration. The Day 5 and 6 predose samples were to check steady state for buprenorphine/naloxone + boceprevir.
Time Frame
Buprenorphine/naloxone samples collected Day 1, 0 (predose) through 24 hours post-dose (Day 2). Boceprevir and buprenorphine/naloxone samples collected Day 7, 0 (predose) through 24 hours post-dose (Day 8). Predose samples also collected on Days 5-6.
Secondary Outcome Measure Information:
Title
AUC of Naloxone (Administered in Combination With Buprenorphine) at Steady State With or Without Boceprevir
Description
AUC is a measure of the amount of drug in the blood over time, measured at steady state (time at which the amount of drug eliminated by the body is in equilibrium with the amount taken in). The Day 1, 0 through 24 hour samples were for buprenorphine/naloxone levels in the absence of boceprevir co-administration. The Day 7, 0 through 24 hour samples were for buprenorphine/naloxone levels in the presence of boceprevir co-administration. The Day 5 and 6 predose samples were to check steady state for buprenorphine/naloxone + boceprevir.
Time Frame
Buprenorphine/naloxone samples collected Day 1, 0 (predose) through 24 hours post-dose (Day 2). Boceprevir and buprenorphine/naloxone samples collected Day 7, 0 (predose) through 24 hours post-dose (Day 8). Predose samples also collected on Days 5-6.
Title
Cmax of Naloxone (Administered in Combination With Buprenorphine) at Steady State With or Without Boceprevir
Description
Cmax is a measure of the maximum level of drug in the blood, measured at steady state (time at which the amount of drug eliminated by the body is in equilibrium with the amount taken in). The Day 1, 0 through 24 hour samples were for buprenorphine/naloxone levels in the absence of boceprevir co-administration. The Day 7, 0 through 24 hour samples were for buprenorphine/naloxone levels in the presence of boceprevir co-administration. The Day 5 and 6 predose samples were to check steady state for buprenorphine/naloxone + boceprevir.
Time Frame
Buprenorphine/naloxone samples collected Day 1, 0 (predose) through 24 hours post-dose (Day 2). Boceprevir and buprenorphine/naloxone samples collected Day 7, 0 (predose) through 24 hours post-dose (Day 8). Predose samples also collected on Days 5-6.
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Body Mass Index (BMI) between 18 and 36, inclusive
Reliable participation in a methadone maintenance or buprenorphine maintenance or buprenorphine/naloxone maintenance program for at least two (2) months prior to Day 1.
Is receiving once daily oral dose of methadone therapy at a stable
individualized dose for at least 4 weeks, receiving once
daily buprenorphine dose at a stable individualized dose for at 4 weeks with, if on buprenorphine only therapy, naloxone added for at least 2 weeks prior to Day 1.
12-lead electrocardiogram (ECG) conduction intervals within gender-specific normal range
Vital signs within normal range
Clinical laboratory tests within normal range
Women who are postmenopausal, surgically sterilized, or premenopausal and use a medically-accepted method of contraception.
Exclusion Criteria:
Pregnancy, breast feeding, or intention to become pregnant or father a child while on study or within 3 months after end of trial
History or presence of inflammatory bowel disease, ulcers, or gastrointestinal or rectal bleeding
History of major gastrointestinal tract surgery such as gastrectomy, gastroenterostomy, or bowel resection
History of pancreatic injury or pancreatitis
History or presence of liver disease or liver injury
History or presence of impaired renal function
History of urinary obstruction or difficulty in voiding
History of any infectious disease within 4 weeks prior to drug administration that in the opinion of the investigator, affects the subject's ability to participate in the trial
Positive for hepatitis B surface antigen, hepatitis C antibodies or human immunodeficiency virus (HIV)
Positive screen for drugs with a high potential for abuse such as cocaine, amphetamines, methylenedioxymethamphetamine (MDMA), barbiturates, benzodiazepines, or opiates/opioids
Excessive use of alcohol in the 2 weeks prior to Day -1, defined as greater than 3 glasses of alcoholic beverages (1 is approximately equivalent to: beer [284 mL/10 oz], wine
[125 mL/4 oz], or distilled spirits [25 mL/1 oz]) per day.
Blood donation in the past 60 days
Previous administration of SCH 503034 (boceprevir)
Current participation in another clinical study or participation in a clinical study (e.g., laboratory or clinical evaluation) within 30 days of baseline
Study staff personnel or family members of the study staff personnel
Demonstrated allergic reactions (eg, food, drug, atopic reactions or asthmatic episodes) that, in the opinion of the investigator and sponsor, interfere with their ability to participate in the trial
History of malignancy within 5 years from Screening
Consumption of excessive amounts (equivalent to > 6 cups of brewed coffee/day) of coffee, tea, cola or other caffeinated beverages
Receipt of any of the following more recently than the washout period prior to Baseline: inhibitors or inducers of cytochrome (CYP) P450, CYP2B6, CYP3A4, and CYP2D6; or oral contraceptives containing drospirenone
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
http://www.merck.com/clinical-trials/pdf/Merck%20Procedure%20on%20Clinical%20Trial%20Data%20Access%20Final_Updated%20July_9_2014.pdf
http://engagezone.msd.com/ds_documentation.php
Citations:
PubMed Identifier
25666027
Citation
Hulskotte EG, Bruce RD, Feng HP, Webster LR, Xuan F, Lin WH, O'Mara E, Wagner JA, Butterton JR. Pharmacokinetic interaction between HCV protease inhibitor boceprevir and methadone or buprenorphine in subjects on stable maintenance therapy. Eur J Clin Pharmacol. 2015 Mar;71(3):303-11. doi: 10.1007/s00228-014-1789-4. Epub 2015 Feb 11.
Results Reference
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A Study to Evaluate the Pharmacokinetic Effect of SCH 503034 (Boceprevir) on Methadone or Buprenorphine/Naloxone Plasma Concentrations (P08123)
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