Trial Outcomes & Findings for A Study to Evaluate the Pharmacokinetic Effect of SCH 503034 (Boceprevir) on Methadone or Buprenorphine/Naloxone Plasma Concentrations (P08123) (NCT NCT01396005)

Last Updated: 2017-04-07

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

21 participants

Primary outcome timeframe

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.

Results posted on

2017-04-07

Participant Flow

Participant milestones

Participant milestones
Measure	Methadone + Boceprevir 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)	Buprenorphine/Naloxone + Boceprevir 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
Overall Study STARTED	10	11
Overall Study COMPLETED	10	9
Overall Study NOT COMPLETED	0	2

Reasons for withdrawal

Reasons for withdrawal
Measure	Methadone + Boceprevir 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)	Buprenorphine/Naloxone + Boceprevir 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
Overall Study Withdrawal by Subject	0	1
Overall Study Non-compliance with protocol	0	1

Baseline Characteristics

A Study to Evaluate the Pharmacokinetic Effect of SCH 503034 (Boceprevir) on Methadone or Buprenorphine/Naloxone Plasma Concentrations (P08123)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Methadone + Boceprevir n=10 Participants 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)	Buprenorphine/Naloxone + Boceprevir n=11 Participants 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	Total n=21 Participants Total of all reporting groups
Age, Continuous	34.2 years STANDARD_DEVIATION 10.2 • n=93 Participants	33.2 years STANDARD_DEVIATION 29.0 • n=4 Participants	33.7 years STANDARD_DEVIATION 10.1 • n=27 Participants
Sex: Female, Male Female	2 Participants n=93 Participants	2 Participants n=4 Participants	4 Participants n=27 Participants
Sex: Female, Male Male	8 Participants n=93 Participants	9 Participants n=4 Participants	17 Participants n=27 Participants

PRIMARY outcome

Timeframe: 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.

Population: All participants receiving standard methadone maintenance therapy + boceprevir

Outcome measures

Outcome measures
Measure	Methadone Alone n=10 Participants 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)	Methadone + Boceprevir n=10 Participants 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)
Area Under the Concentration Versus Time Curve (AUC) at Steady State of Methadone Enantiomers When Administered With or Without Boceprevir R-methadone	50.1 (ng.hr/mL)/mg Geometric Coefficient of Variation 29	42.4 (ng.hr/mL)/mg Geometric Coefficient of Variation 23
Area Under the Concentration Versus Time Curve (AUC) at Steady State of Methadone Enantiomers When Administered With or Without Boceprevir S-methadone	56.9 (ng.hr/mL)/mg Geometric Coefficient of Variation 52	44.6 (ng.hr/mL)/mg Geometric Coefficient of Variation 43

PRIMARY outcome

Population: All participants receiving standard methadone maintenance therapy + 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.

Outcome measures

Outcome measures
Measure	Methadone Alone n=10 Participants 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)	Methadone + Boceprevir n=10 Participants 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)
Maximum Concentration (Cmax) at Steady State of Methadone Enantiomers When Administered With or Without Boceprevir R-methadone	2.94 (ng/mL)/mg Geometric Coefficient of Variation 22	2.63 (ng/mL)/mg Geometric Coefficient of Variation 59
Maximum Concentration (Cmax) at Steady State of Methadone Enantiomers When Administered With or Without Boceprevir S-methadone	3.69 (ng/mL)/mg Geometric Coefficient of Variation 39	3.07 (ng/mL)/mg Geometric Coefficient of Variation 69

PRIMARY outcome

Timeframe: 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.

Population: All participants on Day 1; 2 participants were discontinued from study (Days 2-8).

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.

Outcome measures

Outcome measures
Measure	Methadone Alone n=11 Participants 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)	Methadone + Boceprevir n=9 Participants 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)
AUC of Buprenorphine (Administered in Combination With Naloxone) at Steady State With or Without Boceprevir	3020 (pg.hr/mL)/mg Geometric Coefficient of Variation 55	4040 (pg.hr/mL)/mg Geometric Coefficient of Variation 43

PRIMARY outcome

Population: All participants on Day 1; 1 participant discontinued from study on Day 6.

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.

Outcome measures

Outcome measures
Measure	Methadone Alone n=11 Participants 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)	Methadone + Boceprevir n=10 Participants 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)
Cmax of Buprenorphine (Administered in Combination With Naloxone) at Steady State With or Without Boceprevir	440 (pg/mL)/mg Geometric Coefficient of Variation 52	545 (pg/mL)/mg Geometric Coefficient of Variation 45

SECONDARY outcome

Population: All participants on Day 1; 2 participants were discontinued from study (Days 2-8).

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.

Outcome measures

Outcome measures
Measure	Methadone Alone n=11 Participants 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)	Methadone + Boceprevir n=9 Participants 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)
AUC of Naloxone (Administered in Combination With Buprenorphine) at Steady State With or Without Boceprevir	157 (pg.hr/mL)/mg Geometric Coefficient of Variation 62	224 (pg.hr/mL)/mg Geometric Coefficient of Variation 56

SECONDARY outcome

Population: All participants on Day 1; 1 participant discontinued on Day 6.

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.

Outcome measures

Outcome measures
Measure	Methadone Alone n=11 Participants 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)	Methadone + Boceprevir n=10 Participants 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)
Cmax of Naloxone (Administered in Combination With Buprenorphine) at Steady State With or Without Boceprevir	58.5 (pg/mL)/mg Geometric Coefficient of Variation 87	65.2 (pg/mL)/mg Geometric Coefficient of Variation 70

Adverse Events

Methadone + Boceprevir

Serious events: 0 serious events

Other events: 10 other events

Deaths: 0 deaths

Buprenorphine/Naloxone + Boceprevir

Serious events: 0 serious events

Other events: 9 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Methadone + Boceprevir n=10 participants at risk 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)	Buprenorphine/Naloxone + Boceprevir n=11 participants at risk 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
Gastrointestinal disorders Abdominal pain upper	10.0% 1/10 • Number of events 1	0.00% 0/11
Gastrointestinal disorders Dry mouth	20.0% 2/10 • Number of events 2	9.1% 1/11 • Number of events 1
Gastrointestinal disorders Flatulence	10.0% 1/10 • Number of events 1	0.00% 0/11
Gastrointestinal disorders Nausea	30.0% 3/10 • Number of events 3	18.2% 2/11 • Number of events 3
Gastrointestinal disorders Vomiting	20.0% 2/10 • Number of events 2	0.00% 0/11
General disorders Product taste abnormal	20.0% 2/10 • Number of events 2	9.1% 1/11 • Number of events 1
Infections and infestations Pharyngitis streptococcal	0.00% 0/10	9.1% 1/11 • Number of events 1
Musculoskeletal and connective tissue disorders Muscle spasms	10.0% 1/10 • Number of events 1	0.00% 0/11
Nervous system disorders Dysgeusia	20.0% 2/10 • Number of events 2	45.5% 5/11 • Number of events 5
Nervous system disorders Headache	30.0% 3/10 • Number of events 4	27.3% 3/11 • Number of events 4
Nervous system disorders Somnolence	30.0% 3/10 • Number of events 3	0.00% 0/11
Renal and urinary disorders Pollakiuria	20.0% 2/10 • Number of events 2	18.2% 2/11 • Number of events 2
Respiratory, thoracic and mediastinal disorders Throat irritation	10.0% 1/10 • Number of events 1	0.00% 0/11
Skin and subcutaneous tissue disorders Erythema	0.00% 0/10	9.1% 1/11 • Number of events 1
Skin and subcutaneous tissue disorders Pruritus	0.00% 0/10	9.1% 1/11 • Number of events 1
Skin and subcutaneous tissue disorders Pruritus generalized	0.00% 0/10	9.1% 1/11 • Number of events 1
Vascular disorders Thrombophlebitis	0.00% 0/10	9.1% 1/11 • Number of events 1

Additional Information

Senior Vice President, Global Clinical Development

Merck Sharp & Dohme Corp.

Phone: 1-800-672-6327

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The investigator agrees to provide to the Sponsor 45 days prior to submission for publication or presentation, review copies of abstracts or manuscripts for publication (including, without limitation, slides and texts of oral or other public presentations and texts of any transmission through any electronic media, eg, any computer access system such as the Internet, World Wide Web, etc) that report any results of the trial.
Publication restrictions are in place

Restriction type: OTHER