Trial Outcomes & Findings for Comparison of Safety and Resulting Blood Level Profiles After Administration of a New Boceprevir Tablet Versus Its Current Capsule Formulation for Treatment of Chronic Hepatitis C (P06992)(COMPLETED) (NCT NCT01181804)
NCT ID: NCT01181804
Last Updated: 2017-04-07
Results Overview
AUC is the measure of total plasma exposure of a drug over a given time period. AUC is derived from the area under the plasma drug concentration-time curve.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
177 participants
Primary outcome timeframe
Predose through 72 hours post-dose
Results posted on
2017-04-07
Participant Flow
Participant milestones
| Measure |
Boceprevir Tablets Then Capsules ( Fed)
Participants will start therapy with a single dose of boceprevir tablets, orally, in fed condition, and then 4 days later will take a single dose of boceprevir capsules, orally, in fed condition.
|
Boceprevir Capsules Then Tablets ( Fed)
Participants will start therapy with a single dose of boceprevir capsules, orally, in fed condition, and then 4 days later will take a single dose of boceprevir tablets, orally, in fed condition.
|
Boceprevir Tablets Then Capsules (Fasted)
Participants will start therapy with a single dose of boceprevir tablets, orally, following an overnight fast and then 4 days later will receive a single dose of boceprevir capsules, orally, following and overnight fast.
|
Boceprevir Capsules Then Tablets (Fasted)
Participants will start therapy with a single dose of boceprevir capsules, orally, following an overnight fast and then 4 days later will receive a single dose of boceprevir tablets, orally, following and overnight fast.
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|---|---|---|---|---|
|
Period 1, Fed (Part 1)
STARTED
|
30
|
30
|
0
|
0
|
|
Period 1, Fed (Part 1)
COMPLETED
|
30
|
30
|
0
|
0
|
|
Period 1, Fed (Part 1)
NOT COMPLETED
|
0
|
0
|
0
|
0
|
|
Period 2, Fed (Part 1)
STARTED
|
30
|
30
|
0
|
0
|
|
Period 2, Fed (Part 1)
COMPLETED
|
30
|
30
|
0
|
0
|
|
Period 2, Fed (Part 1)
NOT COMPLETED
|
0
|
0
|
0
|
0
|
|
Period 3, Fasted (Part 2)
STARTED
|
0
|
0
|
59
|
58
|
|
Period 3, Fasted (Part 2)
COMPLETED
|
0
|
0
|
59
|
58
|
|
Period 3, Fasted (Part 2)
NOT COMPLETED
|
0
|
0
|
0
|
0
|
|
Period 4, Fasted (Part 2)
STARTED
|
0
|
0
|
59
|
58
|
|
Period 4, Fasted (Part 2)
COMPLETED
|
0
|
0
|
58
|
58
|
|
Period 4, Fasted (Part 2)
NOT COMPLETED
|
0
|
0
|
1
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Comparison of Safety and Resulting Blood Level Profiles After Administration of a New Boceprevir Tablet Versus Its Current Capsule Formulation for Treatment of Chronic Hepatitis C (P06992)(COMPLETED)
Baseline characteristics by cohort
| Measure |
Boceprevir Tablets Then Capsules (Fed)
n=30 Participants
Participants will start therapy with a single dose of boceprevir tablets, orally, in fed condition, and then 4 days later will take a single dose of boceprevir capsules, orally, in fed condition.
|
Boceprevir Capsules Then Tablets (Fed)
n=30 Participants
Participants will start therapy with a single dose of boceprevir capsules, orally, in fed condition, and then 4 days later will take a single dose of boceprevir tablets, orally, in fed condition.
|
Boceprevir Tablets Then Capsules (Fasted)
n=59 Participants
Participants will start therapy with a single dose of boceprevir tablets, orally, following an overnight fast and then 4 days later will receive a single dose of boceprevir capsules, orally, following and overnight fast.
|
Boceprevir Capsules Then Tablets (Fasted)
n=58 Participants
Participants will start therapy with a single dose of boceprevir capsules, orally, following an overnight fast and then 4 days later will receive a single dose of boceprevir tablets, orally, following and overnight fast.
|
Total
n=177 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=31 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
30 Participants
n=99 Participants
|
30 Participants
n=107 Participants
|
59 Participants
n=206 Participants
|
58 Participants
n=7 Participants
|
177 Participants
n=31 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=31 Participants
|
|
Sex: Female, Male
Female
|
10 Participants
n=99 Participants
|
18 Participants
n=107 Participants
|
27 Participants
n=206 Participants
|
39 Participants
n=7 Participants
|
94 Participants
n=31 Participants
|
|
Sex: Female, Male
Male
|
20 Participants
n=99 Participants
|
12 Participants
n=107 Participants
|
32 Participants
n=206 Participants
|
19 Participants
n=7 Participants
|
83 Participants
n=31 Participants
|
PRIMARY outcome
Timeframe: Predose through 72 hours post-dosePopulation: Analysis is per protocol; all available data are included in the model. No imputation is used for missing data.
AUC is the measure of total plasma exposure of a drug over a given time period. AUC is derived from the area under the plasma drug concentration-time curve.
Outcome measures
| Measure |
Boceprevir Tablets (Fed)
n=60 Participants
In Part 1 of the study, participants received a single dose of boceprevir (800 mg) in tablet formulation in a cross-over manner during either Period 1 or Period 2 under fed conditions.
|
Boceprevir Capsules (Fed)
n=60 Participants
In Part 1 of the study, participants received a single dose of boceprevir (800 mg) in capsule formulation in a cross-over manner during either Period 1 or Period 2 under fed conditions.
|
|---|---|---|
|
Area Under the Concentration Curve (AUC) From Hour 0 to the Final Quantifiable Sample (AUCtf) for Boceprevir Tablets Versus Capsules in Fed State
|
7385 ng*hr/mL
Interval 6939.0 to 7859.0
|
6644 ng*hr/mL
Interval 6243.0 to 7071.0
|
PRIMARY outcome
Timeframe: Predose through 72 hours post-dosePopulation: Analysis is per protocol; all available data are included in the model. No imputation is used for missing data.
Cmax is the highest plasma drug concentration observed on the plasma concentration-time curve.
Outcome measures
| Measure |
Boceprevir Tablets (Fed)
n=60 Participants
In Part 1 of the study, participants received a single dose of boceprevir (800 mg) in tablet formulation in a cross-over manner during either Period 1 or Period 2 under fed conditions.
|
Boceprevir Capsules (Fed)
n=60 Participants
In Part 1 of the study, participants received a single dose of boceprevir (800 mg) in capsule formulation in a cross-over manner during either Period 1 or Period 2 under fed conditions.
|
|---|---|---|
|
Maximum Plasma Concentration (Cmax) of Boceprevir Tablets Versus Capsules in Fed State
|
2161 ng*hr/mL
Interval 1993.0 to 2343.0
|
1515 ng*hr/mL
Interval 1394.0 to 1642.0
|
PRIMARY outcome
Timeframe: Predose through 72 hours post-dosePopulation: Analysis is per protocol; all available data are included in the model. No imputation is used for missing data.
AUC is the measure of total plasma exposure of a drug over a given time period. AUC is derived from the area under the plasma drug concentration-time curve.
Outcome measures
| Measure |
Boceprevir Tablets (Fed)
n=117 Participants
In Part 1 of the study, participants received a single dose of boceprevir (800 mg) in tablet formulation in a cross-over manner during either Period 1 or Period 2 under fed conditions.
|
Boceprevir Capsules (Fed)
n=117 Participants
In Part 1 of the study, participants received a single dose of boceprevir (800 mg) in capsule formulation in a cross-over manner during either Period 1 or Period 2 under fed conditions.
|
|---|---|---|
|
AUCtf for Boceprevir Tablets Versus Capsules in Fasted State
|
4329 ng*hr/mL
Interval 4109.0 to 4561.0
|
3935 ng*hr/mL
Interval 3734.0 to 4146.0
|
PRIMARY outcome
Timeframe: Predose through 72 hours post-dosePopulation: Analysis is per protocol; all available data are included in the model. No imputation is used for missing data.
Cmax is the highest plasma drug concentration observed on the plasma concentration-time curve.
Outcome measures
| Measure |
Boceprevir Tablets (Fed)
n=117 Participants
In Part 1 of the study, participants received a single dose of boceprevir (800 mg) in tablet formulation in a cross-over manner during either Period 1 or Period 2 under fed conditions.
|
Boceprevir Capsules (Fed)
n=117 Participants
In Part 1 of the study, participants received a single dose of boceprevir (800 mg) in capsule formulation in a cross-over manner during either Period 1 or Period 2 under fed conditions.
|
|---|---|---|
|
Cmax of Boceprevir Tablets Versus Capsules in Fasted State
|
1263 ng/mL
Interval 1196.0 to 1333.0
|
1103 ng/mL
Interval 1044.0 to 1164.0
|
PRIMARY outcome
Timeframe: Predose through 72 hours post-dosePopulation: Analysis is per protocol; all available data are included in the model. No imputation is used for missing data.
AUC is the measure of total plasma exposure of a drug over a given time period. AUC is derived from the area under the plasma drug concentration-time curve.
Outcome measures
| Measure |
Boceprevir Tablets (Fed)
n=57 Participants
In Part 1 of the study, participants received a single dose of boceprevir (800 mg) in tablet formulation in a cross-over manner during either Period 1 or Period 2 under fed conditions.
|
Boceprevir Capsules (Fed)
n=52 Participants
In Part 1 of the study, participants received a single dose of boceprevir (800 mg) in capsule formulation in a cross-over manner during either Period 1 or Period 2 under fed conditions.
|
|---|---|---|
|
AUC From Hour 0 to Infinity (AUCinf) in Fed State
|
7457 ng*hr/mL
Interval 7014.0 to 7928.0
|
6879 ng*hr/mL
Interval 6467.0 to 7318.0
|
PRIMARY outcome
Timeframe: Predose through 72 hours post-dosePopulation: Analysis is per protocol; all available data are included in the model. No imputation is used for missing data.
AUC is the measure of total plasma exposure of a drug over a given time period. AUC is derived from the area under the plasma drug concentration-time curve.
Outcome measures
| Measure |
Boceprevir Tablets (Fed)
n=94 Participants
In Part 1 of the study, participants received a single dose of boceprevir (800 mg) in tablet formulation in a cross-over manner during either Period 1 or Period 2 under fed conditions.
|
Boceprevir Capsules (Fed)
n=84 Participants
In Part 1 of the study, participants received a single dose of boceprevir (800 mg) in capsule formulation in a cross-over manner during either Period 1 or Period 2 under fed conditions.
|
|---|---|---|
|
AUCinf in Fasted State
|
4534 ng*hr/mL
Interval 4285.0 to 4798.0
|
4119 ng*hr/mL
Interval 3885.0 to 4367.0
|
PRIMARY outcome
Timeframe: Predose through 72 hours post-dosePopulation: Analysis is per protocol; all available data are included in the model. No imputation is used for missing data.
T1/2 is the time required for a given drug concentration to decrease by 50%.
Outcome measures
| Measure |
Boceprevir Tablets (Fed)
n=57 Participants
In Part 1 of the study, participants received a single dose of boceprevir (800 mg) in tablet formulation in a cross-over manner during either Period 1 or Period 2 under fed conditions.
|
Boceprevir Capsules (Fed)
n=52 Participants
In Part 1 of the study, participants received a single dose of boceprevir (800 mg) in capsule formulation in a cross-over manner during either Period 1 or Period 2 under fed conditions.
|
|---|---|---|
|
Half Life (t1/2) of Boceprevir in Fed State
|
1.61 hours
Standard Deviation 0.46
|
1.46 hours
Standard Deviation 0.34
|
PRIMARY outcome
Timeframe: Predose through 72 hours post-dosePopulation: Analysis is per protocol; all available data are included in the model. No imputation is used for missing data.
T1/2 is the time required for a given drug concentration to decrease by 50%.
Outcome measures
| Measure |
Boceprevir Tablets (Fed)
n=93 Participants
In Part 1 of the study, participants received a single dose of boceprevir (800 mg) in tablet formulation in a cross-over manner during either Period 1 or Period 2 under fed conditions.
|
Boceprevir Capsules (Fed)
n=82 Participants
In Part 1 of the study, participants received a single dose of boceprevir (800 mg) in capsule formulation in a cross-over manner during either Period 1 or Period 2 under fed conditions.
|
|---|---|---|
|
t1/2 Boceprevir in Fasted State
|
5.33 hours
Standard Deviation 0.73
|
6.39 hours
Standard Deviation 0.84
|
Adverse Events
Boceprevir Tablets (Fed)
Serious events: 0 serious events
Other events: 13 other events
Deaths: 0 deaths
Boceprevir Capsules (Fed)
Serious events: 0 serious events
Other events: 6 other events
Deaths: 0 deaths
Boceprevir Tablets (Fasted)
Serious events: 0 serious events
Other events: 7 other events
Deaths: 0 deaths
Boceprevir Capsules (Fasted)
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 |
Boceprevir Tablets (Fed)
n=60 participants at risk
In Part 1 of the study, participants received a single dose of boceprevir (800 mg) in tablet formulation in a cross-over manner during either Period 1 or Period 2 under fed conditions.
|
Boceprevir Capsules (Fed)
n=60 participants at risk
In Part 1 of the study, participants received a single dose of boceprevir (800 mg) in capsule formulation in a cross-over manner during either Period 1 or Period 2 under fed conditions.
|
Boceprevir Tablets (Fasted)
n=117 participants at risk
In Part 2 of the study, participants received a single dose of boceprevir (800 mg) in tablet formulation in a cross-over manner during either Period 3 or Period 4 under fasted conditions.
|
Boceprevir Capsules (Fasted)
n=117 participants at risk
In Part 2 of the study, participants received a single dose of boceprevir (800 mg) in capsule formulation in a cross-over manner during either Period 3 or Period 4 under fasted conditions.
|
|---|---|---|---|---|
|
Gastrointestinal disorders
Abdominal pain lower
|
11.7%
7/60 • Number of events 7
In this study, participants received two single doses of boceprevir 800 mg, once as capsules and once as tablets, under fed and fasted conditions, in a crossover manner; adverse events were pooled as tablets (fed condition), capsules (fed condition), tablets (fasted condition), or capsules (fasted condition).
|
3.3%
2/60 • Number of events 2
In this study, participants received two single doses of boceprevir 800 mg, once as capsules and once as tablets, under fed and fasted conditions, in a crossover manner; adverse events were pooled as tablets (fed condition), capsules (fed condition), tablets (fasted condition), or capsules (fasted condition).
|
0.00%
0/117
In this study, participants received two single doses of boceprevir 800 mg, once as capsules and once as tablets, under fed and fasted conditions, in a crossover manner; adverse events were pooled as tablets (fed condition), capsules (fed condition), tablets (fasted condition), or capsules (fasted condition).
|
0.00%
0/117
In this study, participants received two single doses of boceprevir 800 mg, once as capsules and once as tablets, under fed and fasted conditions, in a crossover manner; adverse events were pooled as tablets (fed condition), capsules (fed condition), tablets (fasted condition), or capsules (fasted condition).
|
|
Gastrointestinal disorders
Constipation
|
8.3%
5/60 • Number of events 6
In this study, participants received two single doses of boceprevir 800 mg, once as capsules and once as tablets, under fed and fasted conditions, in a crossover manner; adverse events were pooled as tablets (fed condition), capsules (fed condition), tablets (fasted condition), or capsules (fasted condition).
|
6.7%
4/60 • Number of events 4
In this study, participants received two single doses of boceprevir 800 mg, once as capsules and once as tablets, under fed and fasted conditions, in a crossover manner; adverse events were pooled as tablets (fed condition), capsules (fed condition), tablets (fasted condition), or capsules (fasted condition).
|
6.0%
7/117 • Number of events 7
In this study, participants received two single doses of boceprevir 800 mg, once as capsules and once as tablets, under fed and fasted conditions, in a crossover manner; adverse events were pooled as tablets (fed condition), capsules (fed condition), tablets (fasted condition), or capsules (fasted condition).
|
4.3%
5/117 • Number of events 5
In this study, participants received two single doses of boceprevir 800 mg, once as capsules and once as tablets, under fed and fasted conditions, in a crossover manner; adverse events were pooled as tablets (fed condition), capsules (fed condition), tablets (fasted condition), or capsules (fasted condition).
|
|
Reproductive system and breast disorders
Menstruation irregular
|
10.0%
6/60 • Number of events 6
In this study, participants received two single doses of boceprevir 800 mg, once as capsules and once as tablets, under fed and fasted conditions, in a crossover manner; adverse events were pooled as tablets (fed condition), capsules (fed condition), tablets (fasted condition), or capsules (fasted condition).
|
1.7%
1/60 • Number of events 1
In this study, participants received two single doses of boceprevir 800 mg, once as capsules and once as tablets, under fed and fasted conditions, in a crossover manner; adverse events were pooled as tablets (fed condition), capsules (fed condition), tablets (fasted condition), or capsules (fasted condition).
|
0.00%
0/117
In this study, participants received two single doses of boceprevir 800 mg, once as capsules and once as tablets, under fed and fasted conditions, in a crossover manner; adverse events were pooled as tablets (fed condition), capsules (fed condition), tablets (fasted condition), or capsules (fasted condition).
|
0.00%
0/117
In this study, participants received two single doses of boceprevir 800 mg, once as capsules and once as tablets, under fed and fasted conditions, in a crossover manner; adverse events were pooled as tablets (fed condition), capsules (fed condition), tablets (fasted condition), or capsules (fasted condition).
|
Additional Information
Vice President, Late Stage Development Group Leader
Merck Sharp & Dohme Corp
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee The investigator agrees not to publish or publicly present any interim results of the trial without the prior written consent of the sponsor. The investigator further agrees to provide to the sponsor 45 days prior to submission for publication or presentation, review copies of abstracts or manuscripts for publication. The sponsor shall have the right to review and comment.
- Publication restrictions are in place
Restriction type: OTHER