Trial Outcomes & Findings for Relative Bioavailability Trial of L-Praziquantel in Healthy Volunteers (NCT NCT02271984)
NCT ID: NCT02271984
Last Updated: 2018-01-03
Results Overview
The AUC(0-inf) was estimated by determining the total area under the curve of the concentration versus time curve extrapolated to infinity.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
36 participants
Primary outcome timeframe
Pre-dose, 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 5.5, 6.0, 8.0, 12.0, 16 and 24 hours post-dose
Results posted on
2018-01-03
Participant Flow
Subjects were randomized to receive a sequence of 5 treatments over 5 treatment periods. A total of 36 were enrolled subjects, three in each of the 12 possible sequences were distributed.
Participant milestones
| Measure |
ABC1DE
Subjects received a single oral dose of MSC2499550A oral disintegrating tablet (ODT) formulation at 20 milligram per kilogram (mg/kg) dispersed in water (A) in first intervention period followed by single oral dose of current PZQ formulation (Cysticide®) at 40 mg/kg with water (B) in second intervention period followed by a single oral dose of MSC2499550A formulation at 10 mg/kg dispersed in water (C1) in third intervention period under fed conditions followed by a single oral dose of MSC2499550A formulation at 20 mg/kg dispersed in water (D) in fourth intervention period under fasted conditions followed by a single oral dose of MSC2499550A formulation at 20 mg/kg directly disintegrated in the mouth (E) in fifth intervention period under fed condition. There was a wash-out period of at least 7 days between each intervention period.
|
ABDEC1
Subjects received a single oral dose of MSC2499550A ODT formulation at 20 mg/kg dispersed in water (A) in first intervention period followed by single oral dose of current PZQ formulation (Cysticide®) at 40 mg/kg with water (B) in second intervention period under fed condition followed by a single oral dose of MSC2499550A formulation at 20 mg/kg dispersed in water (D) in third intervention period under fasted conditions followed by a single oral dose of MSC2499550A formulation at 20 mg/kg directly disintegrated in the mouth (E) in fourth intervention period followed by a single oral dose of MSC2499550A formulation at 10 mg/kg dispersed in water (C1) in fifth intervention period under fed conditions. There was a wash-out period of at least 7 days between each intervention period.
|
ABEC1D
Subjects received a single oral dose of MSC2499550A ODT formulation at 20 mg/kg dispersed in water (A) in first intervention period followed by single oral dose of current PZQ formulation (Cysticide®) at 40 mg/kg with water (B) in second intervention period followed by a single oral dose of MSC2499550A formulation at 20 mg/kg directly disintegrated in the mouth (E) in third intervention period followed by a single oral dose of MSC2499550A formulation at 10 mg/kg dispersed in water (C1) in fourth intervention period under fed conditions followed by a single oral dose of MSC2499550A formulation at 20 mg/kg dispersed in water (D) in fifth intervention period under fasted conditions. There was a wash-out period of at least 7 days between each intervention period.
|
BAC1DE
Subjects received a single oral dose of current PZQ formulation (Cysticide®) at 40 mg/kg with water (B) in first intervention period followed by a single oral dose of MSC2499550A ODT formulation at 20 mg/kg dispersed in water (A) in second intervention period followed by a single oral dose of MSC2499550A formulation at 10 mg/kg dispersed in water (C1) in third intervention period under fed conditions followed by a single oral dose of MSC2499550A formulation at 20 mg/kg dispersed in water (D) in fourth intervention period under fasted conditions followed by a single oral dose of MSC2499550A formulation at 20 mg/kg directly disintegrated in the mouth (E) in fifth intervention period under fed condition. There was a wash-out period of at least 7 days between each intervention period.
|
BADEC1
Subjects received a single oral dose of current PZQ formulation (Cysticide®) at 40 mg/kg with water (B) in first intervention period followed by a single oral dose of MSC2499550A ODT formulation at 20 mg/kg dispersed in water (A) in second intervention period under fed conditions followed by a single oral dose of MSC2499550A formulation at 20 mg/kg dispersed in water (D) in third intervention period under fasted conditions followed by a single oral dose of MSC2499550A formulation at 20 mg/kg directly disintegrated in the mouth (E) in fourth intervention period followed by a single oral dose of MSC2499550A formulation at 10 mg/kg dispersed in water (C1) in fifth intervention period under fed conditions. There was a wash-out period of at least 7 days between each intervention period.
|
BAEC1D
Subjects received a single oral dose of current PZQ formulation (Cysticide®) at 40 mg/kg with water (B) in first intervention period followed by a single oral dose of MSC2499550A ODT formulation at 20 mg/kg dispersed in water (A) in second intervention period followed by a single oral dose of MSC2499550A formulation at 20 mg/kg directly disintegrated in the mouth (E) in third intervention period followed by a single oral dose of MSC2499550A formulation at 10 mg/kg dispersed in water (C1) in fourth intervention period under fed conditions followed by a single oral dose of MSC2499550A formulation at 20 mg/kg dispersed in water (D) in fifth intervention period under fasted conditions. There was a wash-out period of at least 7 days between each intervention period.
|
ABC2DE
Subjects received a single oral dose of MSC2499550A ODT formulation at 20 mg/kg dispersed in water (A) in first intervention period followed by single oral dose of current PZQ formulation (Cysticide®) at 40 mg/kg with water (B) in second intervention period followed by a single oral dose of MSC2499550A formulation at 30 mg/kg dispersed in water (C2) in third intervention period under fed conditions followed by a single oral dose of MSC2499550A formulation at 20 mg/kg dispersed in water (D) in fourth intervention period under fasted conditions followed by a single oral dose of MSC2499550A formulation at 20 mg/kg directly disintegrated in the mouth (E) in fifth intervention period under fed condition. There was a wash-out period of at least 7 days between each intervention period.
|
ABDEC2
Subjects received a single oral dose of MSC2499550A ODT formulation at 20 mg/kg dispersed in water (A) in first intervention period followed by single oral dose of current PZQ formulation (Cysticide®) at 40 mg/kg with water (B) in second intervention period under fed conditions followed by a single oral dose of MSC2499550A formulation at 20 mg/kg dispersed in water (D) in third intervention period under fasted conditions followed by a single oral dose of MSC2499550A formulation at 20 mg/kg directly disintegrated in the mouth (E) in fourth intervention period followed by a single oral dose of MSC2499550A formulation at 30 mg/kg dispersed in water (C2) in fifth intervention period under fed conditions. There was a wash-out period of at least 7 days between each intervention period.
|
ABEC2D
Subjects received a single oral dose of MSC2499550A ODT formulation at 20 mg/kg dispersed in water (A) in first intervention period followed by single oral dose of current PZQ formulation (Cysticide®) at 40 mg/kg with water (B) in second intervention period followed by a single oral dose of MSC2499550A formulation at 20 mg/kg directly disintegrated in the mouth (E) in third intervention period followed by a single oral dose of MSC2499550A formulation at 30 mg/kg dispersed in water (C2) in fourth intervention period under fed conditions followed by a single oral dose of MSC2499550A formulation at 20 mg/kg dispersed in water (D) in fifth intervention period under fasted conditions. There was a wash-out period of at least 7 days between each intervention period.
|
BAC2DE
Subjects received a single oral dose of current PZQ formulation (Cysticide®) at 40 mg/kg with water (B) in first intervention period followed by a single oral dose of MSC2499550A ODT formulation at 20 mg/kg dispersed in water (A) in second intervention period followed by a single oral dose of MSC2499550A formulation at 30 mg/kg dispersed in water (C2) in third intervention period under fed conditions followed by a single oral dose of MSC2499550A formulation at 20 mg/kg dispersed in water (D) in fourth intervention period under fasted conditions followed by a single oral dose of MSC2499550A formulation at 20 mg/kg directly disintegrated in the mouth (E) in fifth intervention period under fed condition. There was a wash-out period of at least 7 days between each intervention period.
|
BADEC2
Subjects received a single oral dose of current PZQ formulation (Cysticide®) at 40 mg/kg with water (B) in first intervention period followed by a single oral dose of MSC2499550A ODT formulation at 20 mg/kg dispersed in water (A) in second intervention period under fed conditions followed by a single oral dose of MSC2499550A formulation at 20 mg/kg dispersed in water (D) in third intervention period under fasted conditions followed by a single oral dose of MSC2499550A formulation at 20 mg/kg directly disintegrated in the mouth (E) in fourth intervention period followed by a single oral dose of MSC2499550A formulation at 30 mg/kg dispersed in water (C2) in fifth intervention period under fed conditions. There was a wash-out period of at least 7 days between each intervention period.
|
BAEC2D
Subjects received a single oral dose of current PZQ formulation (Cysticide®) at 40 mg/kg with water (B) in first intervention period followed by a single oral dose of MSC2499550A ODT formulation at 20 mg/kg dispersed in water (A) in second intervention period followed by a single oral dose of MSC2499550A formulation at 20 mg/kg directly disintegrated in the mouth (E) in third intervention followed by a single oral dose of MSC2499550A formulation at 30 mg/kg dispersed in water (C2) in fourth intervention under fed conditions followed by a single oral dose of MSC2499550A formulation at 20 mg/kg dispersed in water (D) in fifth intervention period under fasted conditions. There was a wash-out period of at least 7 days between each intervention period.
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|---|---|---|---|---|---|---|---|---|---|---|---|---|
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First Intervention Period (1 Day)
STARTED
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3
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3
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3
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3
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3
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3
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3
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3
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3
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3
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First Intervention Period (1 Day)
COMPLETED
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3
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3
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3
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3
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3
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3
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3
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3
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3
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3
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3
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3
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First Intervention Period (1 Day)
NOT COMPLETED
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0
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0
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0
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0
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0
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0
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0
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0
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0
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0
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Washout Period 1 (7 Days)
STARTED
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3
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3
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3
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3
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3
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3
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3
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Washout Period 1 (7 Days)
COMPLETED
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3
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3
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3
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3
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3
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3
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3
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3
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3
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3
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Washout Period 1 (7 Days)
NOT COMPLETED
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0
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0
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0
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0
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0
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0
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0
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0
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0
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0
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Second Intervention Period (1 Day)
STARTED
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3
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3
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3
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3
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3
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Second Intervention Period (1 Day)
COMPLETED
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3
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3
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3
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3
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3
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3
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Second Intervention Period (1 Day)
NOT COMPLETED
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0
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0
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0
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0
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0
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0
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0
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0
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0
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0
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Washout Period 2 (7 Days)
STARTED
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3
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3
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3
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Washout Period 2 (7 Days)
COMPLETED
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3
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3
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3
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3
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Washout Period 2 (7 Days)
NOT COMPLETED
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0
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0
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0
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0
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0
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0
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Third Intervention Period (1 Day)
STARTED
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3
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3
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Third Intervention Period (1 Day)
COMPLETED
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3
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Third Intervention Period (1 Day)
NOT COMPLETED
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0
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0
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0
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0
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0
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0
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0
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0
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Washout Period 3 (7 Days)
STARTED
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3
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3
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3
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3
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3
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3
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Washout Period 3 (7 Days)
COMPLETED
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3
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3
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3
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3
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3
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3
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3
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3
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Washout Period 3 (7 Days)
NOT COMPLETED
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0
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0
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0
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0
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0
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0
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0
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0
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0
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0
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Fourth Intervention Period (Day 1)
STARTED
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3
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3
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3
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Fourth Intervention Period (Day 1)
COMPLETED
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3
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Fourth Intervention Period (Day 1)
NOT COMPLETED
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0
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0
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0
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0
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Washout Period 4 (7 Days)
STARTED
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3
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3
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3
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3
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3
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3
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Washout Period 4 (7 Days)
COMPLETED
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3
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3
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3
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3
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3
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2
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3
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2
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3
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3
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3
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3
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Washout Period 4 (7 Days)
NOT COMPLETED
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0
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0
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0
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0
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0
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1
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0
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1
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0
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0
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0
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0
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Fifth Intervention Period (1 Day)
STARTED
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3
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3
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3
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3
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3
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2
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3
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2
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3
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3
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3
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Fifth Intervention Period (1 Day)
COMPLETED
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3
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3
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3
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3
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3
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2
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3
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2
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3
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3
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3
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3
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Fifth Intervention Period (1 Day)
NOT COMPLETED
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0
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0
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0
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0
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0
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0
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0
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0
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0
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0
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0
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0
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Reasons for withdrawal
| Measure |
ABC1DE
Subjects received a single oral dose of MSC2499550A oral disintegrating tablet (ODT) formulation at 20 milligram per kilogram (mg/kg) dispersed in water (A) in first intervention period followed by single oral dose of current PZQ formulation (Cysticide®) at 40 mg/kg with water (B) in second intervention period followed by a single oral dose of MSC2499550A formulation at 10 mg/kg dispersed in water (C1) in third intervention period under fed conditions followed by a single oral dose of MSC2499550A formulation at 20 mg/kg dispersed in water (D) in fourth intervention period under fasted conditions followed by a single oral dose of MSC2499550A formulation at 20 mg/kg directly disintegrated in the mouth (E) in fifth intervention period under fed condition. There was a wash-out period of at least 7 days between each intervention period.
|
ABDEC1
Subjects received a single oral dose of MSC2499550A ODT formulation at 20 mg/kg dispersed in water (A) in first intervention period followed by single oral dose of current PZQ formulation (Cysticide®) at 40 mg/kg with water (B) in second intervention period under fed condition followed by a single oral dose of MSC2499550A formulation at 20 mg/kg dispersed in water (D) in third intervention period under fasted conditions followed by a single oral dose of MSC2499550A formulation at 20 mg/kg directly disintegrated in the mouth (E) in fourth intervention period followed by a single oral dose of MSC2499550A formulation at 10 mg/kg dispersed in water (C1) in fifth intervention period under fed conditions. There was a wash-out period of at least 7 days between each intervention period.
|
ABEC1D
Subjects received a single oral dose of MSC2499550A ODT formulation at 20 mg/kg dispersed in water (A) in first intervention period followed by single oral dose of current PZQ formulation (Cysticide®) at 40 mg/kg with water (B) in second intervention period followed by a single oral dose of MSC2499550A formulation at 20 mg/kg directly disintegrated in the mouth (E) in third intervention period followed by a single oral dose of MSC2499550A formulation at 10 mg/kg dispersed in water (C1) in fourth intervention period under fed conditions followed by a single oral dose of MSC2499550A formulation at 20 mg/kg dispersed in water (D) in fifth intervention period under fasted conditions. There was a wash-out period of at least 7 days between each intervention period.
|
BAC1DE
Subjects received a single oral dose of current PZQ formulation (Cysticide®) at 40 mg/kg with water (B) in first intervention period followed by a single oral dose of MSC2499550A ODT formulation at 20 mg/kg dispersed in water (A) in second intervention period followed by a single oral dose of MSC2499550A formulation at 10 mg/kg dispersed in water (C1) in third intervention period under fed conditions followed by a single oral dose of MSC2499550A formulation at 20 mg/kg dispersed in water (D) in fourth intervention period under fasted conditions followed by a single oral dose of MSC2499550A formulation at 20 mg/kg directly disintegrated in the mouth (E) in fifth intervention period under fed condition. There was a wash-out period of at least 7 days between each intervention period.
|
BADEC1
Subjects received a single oral dose of current PZQ formulation (Cysticide®) at 40 mg/kg with water (B) in first intervention period followed by a single oral dose of MSC2499550A ODT formulation at 20 mg/kg dispersed in water (A) in second intervention period under fed conditions followed by a single oral dose of MSC2499550A formulation at 20 mg/kg dispersed in water (D) in third intervention period under fasted conditions followed by a single oral dose of MSC2499550A formulation at 20 mg/kg directly disintegrated in the mouth (E) in fourth intervention period followed by a single oral dose of MSC2499550A formulation at 10 mg/kg dispersed in water (C1) in fifth intervention period under fed conditions. There was a wash-out period of at least 7 days between each intervention period.
|
BAEC1D
Subjects received a single oral dose of current PZQ formulation (Cysticide®) at 40 mg/kg with water (B) in first intervention period followed by a single oral dose of MSC2499550A ODT formulation at 20 mg/kg dispersed in water (A) in second intervention period followed by a single oral dose of MSC2499550A formulation at 20 mg/kg directly disintegrated in the mouth (E) in third intervention period followed by a single oral dose of MSC2499550A formulation at 10 mg/kg dispersed in water (C1) in fourth intervention period under fed conditions followed by a single oral dose of MSC2499550A formulation at 20 mg/kg dispersed in water (D) in fifth intervention period under fasted conditions. There was a wash-out period of at least 7 days between each intervention period.
|
ABC2DE
Subjects received a single oral dose of MSC2499550A ODT formulation at 20 mg/kg dispersed in water (A) in first intervention period followed by single oral dose of current PZQ formulation (Cysticide®) at 40 mg/kg with water (B) in second intervention period followed by a single oral dose of MSC2499550A formulation at 30 mg/kg dispersed in water (C2) in third intervention period under fed conditions followed by a single oral dose of MSC2499550A formulation at 20 mg/kg dispersed in water (D) in fourth intervention period under fasted conditions followed by a single oral dose of MSC2499550A formulation at 20 mg/kg directly disintegrated in the mouth (E) in fifth intervention period under fed condition. There was a wash-out period of at least 7 days between each intervention period.
|
ABDEC2
Subjects received a single oral dose of MSC2499550A ODT formulation at 20 mg/kg dispersed in water (A) in first intervention period followed by single oral dose of current PZQ formulation (Cysticide®) at 40 mg/kg with water (B) in second intervention period under fed conditions followed by a single oral dose of MSC2499550A formulation at 20 mg/kg dispersed in water (D) in third intervention period under fasted conditions followed by a single oral dose of MSC2499550A formulation at 20 mg/kg directly disintegrated in the mouth (E) in fourth intervention period followed by a single oral dose of MSC2499550A formulation at 30 mg/kg dispersed in water (C2) in fifth intervention period under fed conditions. There was a wash-out period of at least 7 days between each intervention period.
|
ABEC2D
Subjects received a single oral dose of MSC2499550A ODT formulation at 20 mg/kg dispersed in water (A) in first intervention period followed by single oral dose of current PZQ formulation (Cysticide®) at 40 mg/kg with water (B) in second intervention period followed by a single oral dose of MSC2499550A formulation at 20 mg/kg directly disintegrated in the mouth (E) in third intervention period followed by a single oral dose of MSC2499550A formulation at 30 mg/kg dispersed in water (C2) in fourth intervention period under fed conditions followed by a single oral dose of MSC2499550A formulation at 20 mg/kg dispersed in water (D) in fifth intervention period under fasted conditions. There was a wash-out period of at least 7 days between each intervention period.
|
BAC2DE
Subjects received a single oral dose of current PZQ formulation (Cysticide®) at 40 mg/kg with water (B) in first intervention period followed by a single oral dose of MSC2499550A ODT formulation at 20 mg/kg dispersed in water (A) in second intervention period followed by a single oral dose of MSC2499550A formulation at 30 mg/kg dispersed in water (C2) in third intervention period under fed conditions followed by a single oral dose of MSC2499550A formulation at 20 mg/kg dispersed in water (D) in fourth intervention period under fasted conditions followed by a single oral dose of MSC2499550A formulation at 20 mg/kg directly disintegrated in the mouth (E) in fifth intervention period under fed condition. There was a wash-out period of at least 7 days between each intervention period.
|
BADEC2
Subjects received a single oral dose of current PZQ formulation (Cysticide®) at 40 mg/kg with water (B) in first intervention period followed by a single oral dose of MSC2499550A ODT formulation at 20 mg/kg dispersed in water (A) in second intervention period under fed conditions followed by a single oral dose of MSC2499550A formulation at 20 mg/kg dispersed in water (D) in third intervention period under fasted conditions followed by a single oral dose of MSC2499550A formulation at 20 mg/kg directly disintegrated in the mouth (E) in fourth intervention period followed by a single oral dose of MSC2499550A formulation at 30 mg/kg dispersed in water (C2) in fifth intervention period under fed conditions. There was a wash-out period of at least 7 days between each intervention period.
|
BAEC2D
Subjects received a single oral dose of current PZQ formulation (Cysticide®) at 40 mg/kg with water (B) in first intervention period followed by a single oral dose of MSC2499550A ODT formulation at 20 mg/kg dispersed in water (A) in second intervention period followed by a single oral dose of MSC2499550A formulation at 20 mg/kg directly disintegrated in the mouth (E) in third intervention followed by a single oral dose of MSC2499550A formulation at 30 mg/kg dispersed in water (C2) in fourth intervention under fed conditions followed by a single oral dose of MSC2499550A formulation at 20 mg/kg dispersed in water (D) in fifth intervention period under fasted conditions. There was a wash-out period of at least 7 days between each intervention period.
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|---|---|---|---|---|---|---|---|---|---|---|---|---|
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Washout Period 4 (7 Days)
Withdrawal by Subject
|
0
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0
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0
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0
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0
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1
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0
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1
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0
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0
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0
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0
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Baseline Characteristics
Relative Bioavailability Trial of L-Praziquantel in Healthy Volunteers
Baseline characteristics by cohort
| Measure |
All Subjects
n=36 Participants
Subjects randomized to receive a single oral dose of MSC2499550A formulation at 20 milligram per kilogram (mg/kg) dispersed in water, current praziquantel (PZQ) formulation (Cysticide®) at 40 mg/kg with water under fed conditions; MSC2499550A formulation at 10 mg/kg or 30 mg/kg dispersed in water under fed condition; MSC2499550A formulation at 20 mg/kg dispersed in water under fasted condition; MSC2499550A formulation at 20 mg/kg directly disintegrated in the mouth without water under fed condition in one of the intervention periods.
|
|---|---|
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Age, Continuous
|
26.3 Years
STANDARD_DEVIATION 6.99 • n=5 Participants
|
|
Sex: Female, Male
Female
|
0 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
36 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Pre-dose, 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 5.5, 6.0, 8.0, 12.0, 16 and 24 hours post-dosePopulation: PK population: all randomized subjects treated according to protocol without relevant violations with respect to factors likely to affect comparability of PK results \& availability of AUC0-inf for MSC2499550A in periods 1 \& 2. Number of "participants analyzed" below (Measured Values) reflects number of participants with non-missing values.
The AUC(0-inf) was estimated by determining the total area under the curve of the concentration versus time curve extrapolated to infinity.
Outcome measures
| Measure |
Treatment A
n=36 Participants
Subjects received a single oral dose of MSC2499550A formulation at 20 milligram per kilogram (mg/kg) dispersed in water under fed condition in one of the intervention periods. There was a wash-out period of at least 7 days between each intervention period.
|
Treatment B
n=36 Participants
Subjects received a single oral dose of current PZQ formulation (Cysticide®) at 40 mg/kg with water, under fed condition in one of the intervention periods. There was a wash-out period of at least 7 days between each of the intervention period.
|
Treatment C1
n=17 Participants
Subjects received a single oral dose of MSC2499550A formulation at 10 mg/kg dispersed in water under fed condition in one of the intervention periods. There was a wash-out period of at least 7 days between each of the intervention period.
|
Treatment C2
n=17 Participants
Subjects received a single oral dose of MSC2499550A formulation at 30 mg/kg dispersed in water under fed condition in one of the intervention periods. There was a wash-out period of at least 7 days between each of the intervention period.
|
Treatment D
n=35 Participants
Subjects received a single oral dose of MSC2499550A formulation at 20 mg/kg dispersed in water in fasted condition in one of the intervention periods. There was a wash-out period of at least 7 days between each of the intervention period.
|
Treatment E
n=36 Participants
Subjects received a single oral dose of MSC2499550A formulation at 20 mg/kg directly disintegrated in the mouth without water under fed conditions in one of the intervention periods. There was a wash-out period of at least 7 days between each of the intervention period.
|
|---|---|---|---|---|---|---|
|
Area Under the Plasma Concentration-time Curve (AUC) From Time Zero to Infinity (AUC0-inf) Adj of L-Praziquantel (L-PZQ) After Dose Adjustment
|
825.2 hour*nanogram per milliliter (h*ng/mL)
Geometric Coefficient of Variation 101.0
|
2066.0 hour*nanogram per milliliter (h*ng/mL)
Geometric Coefficient of Variation 64.7
|
216.7 hour*nanogram per milliliter (h*ng/mL)
Geometric Coefficient of Variation 102.8
|
2324.9 hour*nanogram per milliliter (h*ng/mL)
Geometric Coefficient of Variation 76.4
|
506.2 hour*nanogram per milliliter (h*ng/mL)
Geometric Coefficient of Variation 100.0
|
954.5 hour*nanogram per milliliter (h*ng/mL)
Geometric Coefficient of Variation 96.4
|
SECONDARY outcome
Timeframe: Pre-dose, 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 5.5, 6.0, 8.0, 12.0, 16 and 24 hours post-dosePopulation: The pharmacokinetic (PK) population included all randomized subjects who were treated according to the protocol without relevant protocol violations with respect to factors likely to affect the comparability of PK results and the availability of the primary target variable AUC0-inf for MSC2499550A in periods 1 and 2.
Outcome measures
| Measure |
Treatment A
n=36 Participants
Subjects received a single oral dose of MSC2499550A formulation at 20 milligram per kilogram (mg/kg) dispersed in water under fed condition in one of the intervention periods. There was a wash-out period of at least 7 days between each intervention period.
|
Treatment B
n=36 Participants
Subjects received a single oral dose of current PZQ formulation (Cysticide®) at 40 mg/kg with water, under fed condition in one of the intervention periods. There was a wash-out period of at least 7 days between each of the intervention period.
|
Treatment C1
n=18 Participants
Subjects received a single oral dose of MSC2499550A formulation at 10 mg/kg dispersed in water under fed condition in one of the intervention periods. There was a wash-out period of at least 7 days between each of the intervention period.
|
Treatment C2
n=17 Participants
Subjects received a single oral dose of MSC2499550A formulation at 30 mg/kg dispersed in water under fed condition in one of the intervention periods. There was a wash-out period of at least 7 days between each of the intervention period.
|
Treatment D
n=35 Participants
Subjects received a single oral dose of MSC2499550A formulation at 20 mg/kg dispersed in water in fasted condition in one of the intervention periods. There was a wash-out period of at least 7 days between each of the intervention period.
|
Treatment E
n=36 Participants
Subjects received a single oral dose of MSC2499550A formulation at 20 mg/kg directly disintegrated in the mouth without water under fed conditions in one of the intervention periods. There was a wash-out period of at least 7 days between each of the intervention period.
|
|---|---|---|---|---|---|---|
|
Time to Reach the Maximum Plasma Concentration (Tmax) of L-Praziquantel (L-PZQ)
|
2.500 hour
Interval 0.5 to 4.5
|
2.500 hour
Interval 1.0 to 4.5
|
2.250 hour
Interval 1.0 to 4.5
|
3.000 hour
Interval 1.0 to 4.5
|
2.000 hour
Interval 0.5 to 4.5
|
4.000 hour
Interval 0.5 to 5.0
|
SECONDARY outcome
Timeframe: Pre-dose, 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 5.5, 6.0, 8.0, 12.0, 16 and 24 hours post-dosePopulation: The pharmacokinetic (PK) population included all randomized subjects who were treated according to the protocol without relevant protocol violations with respect to factors likely to affect the comparability of PK results and the availability of the primary target variable AUC0-inf for MSC2499550A in periods 1 and 2.
Time prior to the first measurable (non-zero) concentration (tlag) of drug L-PZQ
Outcome measures
| Measure |
Treatment A
n=36 Participants
Subjects received a single oral dose of MSC2499550A formulation at 20 milligram per kilogram (mg/kg) dispersed in water under fed condition in one of the intervention periods. There was a wash-out period of at least 7 days between each intervention period.
|
Treatment B
n=36 Participants
Subjects received a single oral dose of current PZQ formulation (Cysticide®) at 40 mg/kg with water, under fed condition in one of the intervention periods. There was a wash-out period of at least 7 days between each of the intervention period.
|
Treatment C1
n=18 Participants
Subjects received a single oral dose of MSC2499550A formulation at 10 mg/kg dispersed in water under fed condition in one of the intervention periods. There was a wash-out period of at least 7 days between each of the intervention period.
|
Treatment C2
n=17 Participants
Subjects received a single oral dose of MSC2499550A formulation at 30 mg/kg dispersed in water under fed condition in one of the intervention periods. There was a wash-out period of at least 7 days between each of the intervention period.
|
Treatment D
n=35 Participants
Subjects received a single oral dose of MSC2499550A formulation at 20 mg/kg dispersed in water in fasted condition in one of the intervention periods. There was a wash-out period of at least 7 days between each of the intervention period.
|
Treatment E
n=36 Participants
Subjects received a single oral dose of MSC2499550A formulation at 20 mg/kg directly disintegrated in the mouth without water under fed conditions in one of the intervention periods. There was a wash-out period of at least 7 days between each of the intervention period.
|
|---|---|---|---|---|---|---|
|
Time Prior to the First Measurable (Non-zero) Concentration (Tlag) of L-Praziquantel (L-PZQ)
|
0.0 hour
Interval 0.0 to 0.0
|
0.0 hour
Interval 0.0 to 1.0
|
0.0 hour
Interval 0.0 to 0.0
|
0.0 hour
Interval 0.0 to 0.0
|
0.0 hour
Interval 0.0 to 0.0
|
0.0 hour
Interval 0.0 to 0.0
|
SECONDARY outcome
Timeframe: Pre-dose, 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 5.5, 6.0, 8.0, 12.0, 16 and 24 hours post-dosePopulation: The pharmacokinetic (PK) population included all randomized subjects who were treated according to the protocol without relevant protocol violations with respect to factors likely to affect the comparability of PK results and the availability of the primary target variable AUC0-inf for MSC2499550A in periods 1 and 2.
The AUC (0-t) was defined as the area under the plasma concentration versus time curve from time zero to time of last quantifiable concentration at or above the lower limit of quantification (AUC0-t) of L-PZQ.
Outcome measures
| Measure |
Treatment A
n=36 Participants
Subjects received a single oral dose of MSC2499550A formulation at 20 milligram per kilogram (mg/kg) dispersed in water under fed condition in one of the intervention periods. There was a wash-out period of at least 7 days between each intervention period.
|
Treatment B
n=36 Participants
Subjects received a single oral dose of current PZQ formulation (Cysticide®) at 40 mg/kg with water, under fed condition in one of the intervention periods. There was a wash-out period of at least 7 days between each of the intervention period.
|
Treatment C1
n=18 Participants
Subjects received a single oral dose of MSC2499550A formulation at 10 mg/kg dispersed in water under fed condition in one of the intervention periods. There was a wash-out period of at least 7 days between each of the intervention period.
|
Treatment C2
n=17 Participants
Subjects received a single oral dose of MSC2499550A formulation at 30 mg/kg dispersed in water under fed condition in one of the intervention periods. There was a wash-out period of at least 7 days between each of the intervention period.
|
Treatment D
n=35 Participants
Subjects received a single oral dose of MSC2499550A formulation at 20 mg/kg dispersed in water in fasted condition in one of the intervention periods. There was a wash-out period of at least 7 days between each of the intervention period.
|
Treatment E
n=36 Participants
Subjects received a single oral dose of MSC2499550A formulation at 20 mg/kg directly disintegrated in the mouth without water under fed conditions in one of the intervention periods. There was a wash-out period of at least 7 days between each of the intervention period.
|
|---|---|---|---|---|---|---|
|
Area Under the Plasma Concentration-time Curve (AUC) From Time Zero to the Last Sampling Time at Which the Concentration is at or Above the Lower Limit of Quantification (AUC0-t) of L-Praziquantel (L-PZQ) After Dose Adjustment
|
791.0 hour*nanogram per milliliter (h*ng/mL)
Geometric Coefficient of Variation 103.6
|
2010.7 hour*nanogram per milliliter (h*ng/mL)
Geometric Coefficient of Variation 66.1
|
186.2 hour*nanogram per milliliter (h*ng/mL)
Geometric Coefficient of Variation 107.5
|
2273.5 hour*nanogram per milliliter (h*ng/mL)
Geometric Coefficient of Variation 77.9
|
464.7 hour*nanogram per milliliter (h*ng/mL)
Geometric Coefficient of Variation 102.9
|
918.0 hour*nanogram per milliliter (h*ng/mL)
Geometric Coefficient of Variation 98.7
|
SECONDARY outcome
Timeframe: Pre-dose, 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 5.5, 6.0, 8.0, 12.0, 16 and 24 hours post-dosePopulation: PK population: all randomized subjects treated according to protocol without relevant violations with respect to factors likely to affect comparability of PK results \& availability of AUC0-inf for MSC2499550A in periods 1 \& 2. Number of "participants analyzed" below (Measured Values) reflects number of participants with non-missing values.
Extrapolated AUC from time tlast to infinity given as percentage from AUC0-inf. AUCextra =(last predicted concentration \[Clast pred\] divided by terminal elimination rate constant \[lambda z\]) divided by AUC0-inf., where Clast pred is the last predicted concentration.
Outcome measures
| Measure |
Treatment A
n=36 Participants
Subjects received a single oral dose of MSC2499550A formulation at 20 milligram per kilogram (mg/kg) dispersed in water under fed condition in one of the intervention periods. There was a wash-out period of at least 7 days between each intervention period.
|
Treatment B
n=36 Participants
Subjects received a single oral dose of current PZQ formulation (Cysticide®) at 40 mg/kg with water, under fed condition in one of the intervention periods. There was a wash-out period of at least 7 days between each of the intervention period.
|
Treatment C1
n=17 Participants
Subjects received a single oral dose of MSC2499550A formulation at 10 mg/kg dispersed in water under fed condition in one of the intervention periods. There was a wash-out period of at least 7 days between each of the intervention period.
|
Treatment C2
n=17 Participants
Subjects received a single oral dose of MSC2499550A formulation at 30 mg/kg dispersed in water under fed condition in one of the intervention periods. There was a wash-out period of at least 7 days between each of the intervention period.
|
Treatment D
n=35 Participants
Subjects received a single oral dose of MSC2499550A formulation at 20 mg/kg dispersed in water in fasted condition in one of the intervention periods. There was a wash-out period of at least 7 days between each of the intervention period.
|
Treatment E
n=36 Participants
Subjects received a single oral dose of MSC2499550A formulation at 20 mg/kg directly disintegrated in the mouth without water under fed conditions in one of the intervention periods. There was a wash-out period of at least 7 days between each of the intervention period.
|
|---|---|---|---|---|---|---|
|
Extrapolated Area Under the Concentration Time Curve (AUC) From Time Tlast to Infinity Given as Percentage From AUC0-inf (AUCextra) of L-Praziquantel (L-PZQ)
|
3.40 Percent extrapolated
Geometric Coefficient of Variation 73.8
|
2.20 Percent extrapolated
Geometric Coefficient of Variation 65.2
|
6.62 Percent extrapolated
Geometric Coefficient of Variation 85.3
|
1.80 Percent extrapolated
Geometric Coefficient of Variation 72.7
|
5.81 Percent extrapolated
Geometric Coefficient of Variation 82.5
|
3.15 Percent extrapolated
Geometric Coefficient of Variation 66.5
|
SECONDARY outcome
Timeframe: Pre-dose, 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 5.5, 6.0, 8.0, 12.0, 16 and 24 hours post-dosePopulation: The PK population included all randomized subjects who were treated according to the protocol without relevant protocol violations with respect to factors likely to affect the comparability of PK results and the availability of the primary target variable AUC0-inf for MSC2499550A in periods 1 and 2.
Outcome measures
| Measure |
Treatment A
n=36 Participants
Subjects received a single oral dose of MSC2499550A formulation at 20 milligram per kilogram (mg/kg) dispersed in water under fed condition in one of the intervention periods. There was a wash-out period of at least 7 days between each intervention period.
|
Treatment B
n=36 Participants
Subjects received a single oral dose of current PZQ formulation (Cysticide®) at 40 mg/kg with water, under fed condition in one of the intervention periods. There was a wash-out period of at least 7 days between each of the intervention period.
|
Treatment C1
n=18 Participants
Subjects received a single oral dose of MSC2499550A formulation at 10 mg/kg dispersed in water under fed condition in one of the intervention periods. There was a wash-out period of at least 7 days between each of the intervention period.
|
Treatment C2
n=17 Participants
Subjects received a single oral dose of MSC2499550A formulation at 30 mg/kg dispersed in water under fed condition in one of the intervention periods. There was a wash-out period of at least 7 days between each of the intervention period.
|
Treatment D
n=35 Participants
Subjects received a single oral dose of MSC2499550A formulation at 20 mg/kg dispersed in water in fasted condition in one of the intervention periods. There was a wash-out period of at least 7 days between each of the intervention period.
|
Treatment E
n=36 Participants
Subjects received a single oral dose of MSC2499550A formulation at 20 mg/kg directly disintegrated in the mouth without water under fed conditions in one of the intervention periods. There was a wash-out period of at least 7 days between each of the intervention period.
|
|---|---|---|---|---|---|---|
|
Maximum Observed Concentration in Plasma (Cmax) of L-Praziquantel (L-PZQ) After Dose Adjustment
|
378.83 nanogram per milliliter (ng/mL)
Geometric Coefficient of Variation 114.1
|
727.27 nanogram per milliliter (ng/mL)
Geometric Coefficient of Variation 63.3
|
89.93 nanogram per milliliter (ng/mL)
Geometric Coefficient of Variation 92.2
|
1051.76 nanogram per milliliter (ng/mL)
Geometric Coefficient of Variation 83.6
|
131.06 nanogram per milliliter (ng/mL)
Geometric Coefficient of Variation 110.6
|
471.18 nanogram per milliliter (ng/mL)
Geometric Coefficient of Variation 99.5
|
SECONDARY outcome
Timeframe: Pre-dose, 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 5.5, 6.0, 8.0, 12.0, 16 and 24 hours post-dosePopulation: PK population: all randomized subjects treated according to protocol without relevant violations with respect to factors likely to affect comparability of PK results \& availability of AUC0-inf for MSC2499550A in periods 1 \& 2. Number of "participants analyzed" below (Measured Values) reflects number of participants with non-missing values.
The apparent terminal half-life was calculated by dividing natural log 2 with lambda z (ln2/lambda Z); where lambda Z is the terminal rate constant.
Outcome measures
| Measure |
Treatment A
n=36 Participants
Subjects received a single oral dose of MSC2499550A formulation at 20 milligram per kilogram (mg/kg) dispersed in water under fed condition in one of the intervention periods. There was a wash-out period of at least 7 days between each intervention period.
|
Treatment B
n=36 Participants
Subjects received a single oral dose of current PZQ formulation (Cysticide®) at 40 mg/kg with water, under fed condition in one of the intervention periods. There was a wash-out period of at least 7 days between each of the intervention period.
|
Treatment C1
n=17 Participants
Subjects received a single oral dose of MSC2499550A formulation at 10 mg/kg dispersed in water under fed condition in one of the intervention periods. There was a wash-out period of at least 7 days between each of the intervention period.
|
Treatment C2
n=17 Participants
Subjects received a single oral dose of MSC2499550A formulation at 30 mg/kg dispersed in water under fed condition in one of the intervention periods. There was a wash-out period of at least 7 days between each of the intervention period.
|
Treatment D
n=35 Participants
Subjects received a single oral dose of MSC2499550A formulation at 20 mg/kg dispersed in water in fasted condition in one of the intervention periods. There was a wash-out period of at least 7 days between each of the intervention period.
|
Treatment E
n=36 Participants
Subjects received a single oral dose of MSC2499550A formulation at 20 mg/kg directly disintegrated in the mouth without water under fed conditions in one of the intervention periods. There was a wash-out period of at least 7 days between each of the intervention period.
|
|---|---|---|---|---|---|---|
|
Apparent Terminal Half-life (T1/2) of L-Praziquantel (L-PZQ)
|
2.984 hour
Interval 1.01 to 6.49
|
3.788 hour
Interval 1.44 to 10.1
|
1.059 hour
Interval 0.623 to 7.58
|
3.296 hour
Interval 1.82 to 5.46
|
2.801 hour
Interval 0.869 to 24.9
|
2.711 hour
Interval 0.452 to 6.65
|
SECONDARY outcome
Timeframe: Pre-dose, 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 5.5, 6.0, 8.0, 12.0, 16 and 24 hours post-dosePopulation: The PK population included all randomized subjects who were treated according to the protocol without relevant protocol violations with respect to factors likely to affect the comparability of PK results and the availability of the primary target variable AUC0-inf for MSC2499550A in periods 1 and 2.
Relative bioavailability (Frel) was calculated for L-PZQ only (treatment A versus treatment B) using the formula: Frel = (AUC0-inf (test or Treatment A)/AUC0-inf (reference or treatment B)) multiplied by 100.
Outcome measures
| Measure |
Treatment A
n=36 Participants
Subjects received a single oral dose of MSC2499550A formulation at 20 milligram per kilogram (mg/kg) dispersed in water under fed condition in one of the intervention periods. There was a wash-out period of at least 7 days between each intervention period.
|
Treatment B
Subjects received a single oral dose of current PZQ formulation (Cysticide®) at 40 mg/kg with water, under fed condition in one of the intervention periods. There was a wash-out period of at least 7 days between each of the intervention period.
|
Treatment C1
Subjects received a single oral dose of MSC2499550A formulation at 10 mg/kg dispersed in water under fed condition in one of the intervention periods. There was a wash-out period of at least 7 days between each of the intervention period.
|
Treatment C2
Subjects received a single oral dose of MSC2499550A formulation at 30 mg/kg dispersed in water under fed condition in one of the intervention periods. There was a wash-out period of at least 7 days between each of the intervention period.
|
Treatment D
Subjects received a single oral dose of MSC2499550A formulation at 20 mg/kg dispersed in water in fasted condition in one of the intervention periods. There was a wash-out period of at least 7 days between each of the intervention period.
|
Treatment E
Subjects received a single oral dose of MSC2499550A formulation at 20 mg/kg directly disintegrated in the mouth without water under fed conditions in one of the intervention periods. There was a wash-out period of at least 7 days between each of the intervention period.
|
|---|---|---|---|---|---|---|
|
Relative Bioavailability (Frel) of L-Praziquantel (L-PZQ)
|
40.075 Percentage bioavailability
Interval 33.9 to 47.38
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Pre-dose, 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 5.5, 6.0, 8.0, 12.0, 16 and 24 hours post-dosePopulation: PK population: all randomized subjects treated according to protocol without relevant violations with respect to factors likely to affect comparability of PK results \& availability of AUC0-inf for MSC2499550A in periods 1 \& 2. Number of "participants analyzed" below (Measured Values) reflects number of participants with non-missing values.
The lambda z was calculated as the negative of the slope of the log-linear regression of the natural logarithm concentration-time curve during the terminal phase.
Outcome measures
| Measure |
Treatment A
n=36 Participants
Subjects received a single oral dose of MSC2499550A formulation at 20 milligram per kilogram (mg/kg) dispersed in water under fed condition in one of the intervention periods. There was a wash-out period of at least 7 days between each intervention period.
|
Treatment B
n=36 Participants
Subjects received a single oral dose of current PZQ formulation (Cysticide®) at 40 mg/kg with water, under fed condition in one of the intervention periods. There was a wash-out period of at least 7 days between each of the intervention period.
|
Treatment C1
n=17 Participants
Subjects received a single oral dose of MSC2499550A formulation at 10 mg/kg dispersed in water under fed condition in one of the intervention periods. There was a wash-out period of at least 7 days between each of the intervention period.
|
Treatment C2
n=17 Participants
Subjects received a single oral dose of MSC2499550A formulation at 30 mg/kg dispersed in water under fed condition in one of the intervention periods. There was a wash-out period of at least 7 days between each of the intervention period.
|
Treatment D
n=35 Participants
Subjects received a single oral dose of MSC2499550A formulation at 20 mg/kg dispersed in water in fasted condition in one of the intervention periods. There was a wash-out period of at least 7 days between each of the intervention period.
|
Treatment E
n=36 Participants
Subjects received a single oral dose of MSC2499550A formulation at 20 mg/kg directly disintegrated in the mouth without water under fed conditions in one of the intervention periods. There was a wash-out period of at least 7 days between each of the intervention period.
|
|---|---|---|---|---|---|---|
|
Apparent Terminal Elimination Rate Constant (Lambda Z) of L-Praziquantel (L-PZQ)
|
0.250 per hour (1/hour)
Geometric Coefficient of Variation 53.9
|
0.181 per hour (1/hour)
Geometric Coefficient of Variation 46.3
|
0.432 per hour (1/hour)
Geometric Coefficient of Variation 88.6
|
0.206 per hour (1/hour)
Geometric Coefficient of Variation 31.9
|
0.244 per hour (1/hour)
Geometric Coefficient of Variation 62.3
|
0.264 per hour (1/hour)
Geometric Coefficient of Variation 65.2
|
SECONDARY outcome
Timeframe: Pre-dose, 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 5.5, 6.0, 8.0, 12.0, 16 and 24 hours post-dosePopulation: PK population: all randomized subjects treated according to protocol without relevant violations with respect to factors likely to affect comparability of PK results \& availability of AUC0-inf for MSC2499550A in periods 1 \& 2. Number of "participants analyzed" below (Measured Values) reflects number of participants with non-missing values.
The CL/f of L-PZQ was a measure of the rate at which it was metabolized or eliminated by normal biological processes. Clearance obtained after oral dose was influenced by the fraction of the dose absorbed. The CL/F of L-PZQ from plasma was calculated using the formula: Dose divided by area under the concentration time curve from time zero to infinity (AUC0-inf).
Outcome measures
| Measure |
Treatment A
n=36 Participants
Subjects received a single oral dose of MSC2499550A formulation at 20 milligram per kilogram (mg/kg) dispersed in water under fed condition in one of the intervention periods. There was a wash-out period of at least 7 days between each intervention period.
|
Treatment B
n=36 Participants
Subjects received a single oral dose of current PZQ formulation (Cysticide®) at 40 mg/kg with water, under fed condition in one of the intervention periods. There was a wash-out period of at least 7 days between each of the intervention period.
|
Treatment C1
n=17 Participants
Subjects received a single oral dose of MSC2499550A formulation at 10 mg/kg dispersed in water under fed condition in one of the intervention periods. There was a wash-out period of at least 7 days between each of the intervention period.
|
Treatment C2
n=17 Participants
Subjects received a single oral dose of MSC2499550A formulation at 30 mg/kg dispersed in water under fed condition in one of the intervention periods. There was a wash-out period of at least 7 days between each of the intervention period.
|
Treatment D
n=35 Participants
Subjects received a single oral dose of MSC2499550A formulation at 20 mg/kg dispersed in water in fasted condition in one of the intervention periods. There was a wash-out period of at least 7 days between each of the intervention period.
|
Treatment E
n=36 Participants
Subjects received a single oral dose of MSC2499550A formulation at 20 mg/kg directly disintegrated in the mouth without water under fed conditions in one of the intervention periods. There was a wash-out period of at least 7 days between each of the intervention period.
|
|---|---|---|---|---|---|---|
|
Apparent Total Body Clearance of Drug From Plasma (CL/f) of L-Praziquantel (L-PZQ)
|
1665 Liter per hour
Geometric Coefficient of Variation 94.3
|
667.3 Liter per hour
Geometric Coefficient of Variation 60.1
|
3091 Liter per hour
Geometric Coefficient of Variation 92.9
|
923.5 Liter per hour
Geometric Coefficient of Variation 71.4
|
2729 Liter per hour
Geometric Coefficient of Variation 95.4
|
1440 Liter per hour
Geometric Coefficient of Variation 89.3
|
SECONDARY outcome
Timeframe: Pre-dose, 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 5.5, 6.0, 8.0, 12.0, 16 and 24 hours post-dosePopulation: PK population: all randomized subjects treated according to protocol without relevant violations with respect to factors likely to affect comparability of PK results \& availability of AUC0-inf for MSC2499550A in periods 1 \& 2. Number of "participants analyzed" below (Measured Values) reflects number of participants with non-missing values.
The Vz/f was defined as the theoretical volume in which the total amount of L-PZQ required to uniformly distribute to produce the desired plasma concentration of L-PZQ. Apparent volume of distribution after oral dose (Vz/F) was influenced by the fraction absorbed. The Vz/f was calculated by dividing the dose with area under the concentration time curve from time zero to infinity multiplied with terminal elimination rate constant (lambda z) (Vz/f=Dose/( AUC0-inf\* lambda z).
Outcome measures
| Measure |
Treatment A
n=36 Participants
Subjects received a single oral dose of MSC2499550A formulation at 20 milligram per kilogram (mg/kg) dispersed in water under fed condition in one of the intervention periods. There was a wash-out period of at least 7 days between each intervention period.
|
Treatment B
n=36 Participants
Subjects received a single oral dose of current PZQ formulation (Cysticide®) at 40 mg/kg with water, under fed condition in one of the intervention periods. There was a wash-out period of at least 7 days between each of the intervention period.
|
Treatment C1
n=17 Participants
Subjects received a single oral dose of MSC2499550A formulation at 10 mg/kg dispersed in water under fed condition in one of the intervention periods. There was a wash-out period of at least 7 days between each of the intervention period.
|
Treatment C2
n=17 Participants
Subjects received a single oral dose of MSC2499550A formulation at 30 mg/kg dispersed in water under fed condition in one of the intervention periods. There was a wash-out period of at least 7 days between each of the intervention period.
|
Treatment D
n=35 Participants
Subjects received a single oral dose of MSC2499550A formulation at 20 mg/kg dispersed in water in fasted condition in one of the intervention periods. There was a wash-out period of at least 7 days between each of the intervention period.
|
Treatment E
n=36 Participants
Subjects received a single oral dose of MSC2499550A formulation at 20 mg/kg directly disintegrated in the mouth without water under fed conditions in one of the intervention periods. There was a wash-out period of at least 7 days between each of the intervention period.
|
|---|---|---|---|---|---|---|
|
Apparent Volume of Distribution During the Terminal Phase (Vz/f) of L-Praziquantel (L-PZQ)
|
6671 Liter
Geometric Coefficient of Variation 62.9
|
3685 Liter
Geometric Coefficient of Variation 62.8
|
7155 Liter
Geometric Coefficient of Variation 72.4
|
4478 Liter
Geometric Coefficient of Variation 62.8
|
11170 Liter
Geometric Coefficient of Variation 81.1
|
5452 Liter
Geometric Coefficient of Variation 62.4
|
SECONDARY outcome
Timeframe: From the first dose of study drug administration up to 3-10 days after the last dose of the study drug (up to a maximum of 7 weeks)Population: The safety analysis set consisted of all subjects who received at least one dose of the trial medication and who had follow-up safety assessments.
An Adverse Event (AE) was defined as any new untoward medical occurrences/worsening of pre-existing medical condition without regard to possibility of causal relationship. A Serious Adverse Event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect. TEAEs were adverse events that occurred between the first dose of study drug and up to 3-10 days after the last dose that were absent before treatment or that worsened relative to pretreatment state. Subjects who discontinued and who died due to TEAEs were also reported.
Outcome measures
| Measure |
Treatment A
n=36 Participants
Subjects received a single oral dose of MSC2499550A formulation at 20 milligram per kilogram (mg/kg) dispersed in water under fed condition in one of the intervention periods. There was a wash-out period of at least 7 days between each intervention period.
|
Treatment B
n=36 Participants
Subjects received a single oral dose of current PZQ formulation (Cysticide®) at 40 mg/kg with water, under fed condition in one of the intervention periods. There was a wash-out period of at least 7 days between each of the intervention period.
|
Treatment C1
n=18 Participants
Subjects received a single oral dose of MSC2499550A formulation at 10 mg/kg dispersed in water under fed condition in one of the intervention periods. There was a wash-out period of at least 7 days between each of the intervention period.
|
Treatment C2
n=17 Participants
Subjects received a single oral dose of MSC2499550A formulation at 30 mg/kg dispersed in water under fed condition in one of the intervention periods. There was a wash-out period of at least 7 days between each of the intervention period.
|
Treatment D
n=35 Participants
Subjects received a single oral dose of MSC2499550A formulation at 20 mg/kg dispersed in water in fasted condition in one of the intervention periods. There was a wash-out period of at least 7 days between each of the intervention period.
|
Treatment E
n=36 Participants
Subjects received a single oral dose of MSC2499550A formulation at 20 mg/kg directly disintegrated in the mouth without water under fed conditions in one of the intervention periods. There was a wash-out period of at least 7 days between each of the intervention period.
|
|---|---|---|---|---|---|---|
|
Number of Subjects With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs, TEAEs Leading to Death and TEAEs Leading to Discontinuation
TEAEs
|
8 Subjects
|
17 Subjects
|
4 Subjects
|
4 Subjects
|
5 Subjects
|
1 Subjects
|
|
Number of Subjects With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs, TEAEs Leading to Death and TEAEs Leading to Discontinuation
Serious TEAEs
|
0 Subjects
|
0 Subjects
|
0 Subjects
|
0 Subjects
|
0 Subjects
|
0 Subjects
|
|
Number of Subjects With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs, TEAEs Leading to Death and TEAEs Leading to Discontinuation
TEAEs leading to discontinuation
|
0 Subjects
|
0 Subjects
|
0 Subjects
|
0 Subjects
|
0 Subjects
|
0 Subjects
|
|
Number of Subjects With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs, TEAEs Leading to Death and TEAEs Leading to Discontinuation
TEAEs leading to death
|
0 Subjects
|
0 Subjects
|
0 Subjects
|
0 Subjects
|
0 Subjects
|
0 Subjects
|
SECONDARY outcome
Timeframe: 0 min for flavor, smell, sweetness, overall liking; 2-5 minutes post dose for taste in mouth and acceptability on Day 1Population: The safety analysis set consisted of all subjects who received at least one dose of the trial medication and who had follow-up safety assessments.
Each administration was assessed at 0 minutes on Day 1 for flavor, smell, sweetness, overall liking of the medicine and at 2-5 minutes on Day 1 for taste in mouth and acceptability to swallow using a modified 100 millimeter (mm), visual analog scale (VAS) incorporating a facial hedonic scale, where lower score (0) indicates "not acceptable/not liked at all" and higher score (100) indicates "very acceptable/liked very much".
Outcome measures
| Measure |
Treatment A
n=36 Participants
Subjects received a single oral dose of MSC2499550A formulation at 20 milligram per kilogram (mg/kg) dispersed in water under fed condition in one of the intervention periods. There was a wash-out period of at least 7 days between each intervention period.
|
Treatment B
n=36 Participants
Subjects received a single oral dose of current PZQ formulation (Cysticide®) at 40 mg/kg with water, under fed condition in one of the intervention periods. There was a wash-out period of at least 7 days between each of the intervention period.
|
Treatment C1
n=18 Participants
Subjects received a single oral dose of MSC2499550A formulation at 10 mg/kg dispersed in water under fed condition in one of the intervention periods. There was a wash-out period of at least 7 days between each of the intervention period.
|
Treatment C2
n=17 Participants
Subjects received a single oral dose of MSC2499550A formulation at 30 mg/kg dispersed in water under fed condition in one of the intervention periods. There was a wash-out period of at least 7 days between each of the intervention period.
|
Treatment D
n=35 Participants
Subjects received a single oral dose of MSC2499550A formulation at 20 mg/kg dispersed in water in fasted condition in one of the intervention periods. There was a wash-out period of at least 7 days between each of the intervention period.
|
Treatment E
n=36 Participants
Subjects received a single oral dose of MSC2499550A formulation at 20 mg/kg directly disintegrated in the mouth without water under fed conditions in one of the intervention periods. There was a wash-out period of at least 7 days between each of the intervention period.
|
|---|---|---|---|---|---|---|
|
Palatability Score
Flavor: Day 1: 0 min
|
67.5 millimeter (mm)
Standard Deviation 22.19
|
45.8 millimeter (mm)
Standard Deviation 24.04
|
72.2 millimeter (mm)
Standard Deviation 27.17
|
68.8 millimeter (mm)
Standard Deviation 22.33
|
65.9 millimeter (mm)
Standard Deviation 22.95
|
32.9 millimeter (mm)
Standard Deviation 29.10
|
|
Palatability Score
Smell: Day 1: 0 min
|
63.1 millimeter (mm)
Standard Deviation 21.63
|
56.4 millimeter (mm)
Standard Deviation 26.32
|
64.8 millimeter (mm)
Standard Deviation 25.22
|
61.9 millimeter (mm)
Standard Deviation 21.64
|
64.6 millimeter (mm)
Standard Deviation 19.67
|
46.9 millimeter (mm)
Standard Deviation 26.17
|
|
Palatability Score
Sweetness: Day 1: 0 min
|
74.8 millimeter (mm)
Standard Deviation 19.42
|
30.5 millimeter (mm)
Standard Deviation 20.80
|
72.2 millimeter (mm)
Standard Deviation 23.97
|
73.0 millimeter (mm)
Standard Deviation 19.31
|
68.0 millimeter (mm)
Standard Deviation 22.12
|
40.8 millimeter (mm)
Standard Deviation 30.59
|
|
Palatability Score
Overall liking of Medicine: Day 1: 0 min
|
67.8 millimeter (mm)
Standard Deviation 21.75
|
47.0 millimeter (mm)
Standard Deviation 28.22
|
69.7 millimeter (mm)
Standard Deviation 26.21
|
68.0 millimeter (mm)
Standard Deviation 20.47
|
63.3 millimeter (mm)
Standard Deviation 23.86
|
53.2 millimeter (mm)
Standard Deviation 26.10
|
|
Palatability Score
Taste in Mouth: Day 1:2-5 minutes after medication
|
50.9 millimeter (mm)
Standard Deviation 26.42
|
39.5 millimeter (mm)
Standard Deviation 26.12
|
68.9 millimeter (mm)
Standard Deviation 27.77
|
47.1 millimeter (mm)
Standard Deviation 28.29
|
47.7 millimeter (mm)
Standard Deviation 26.82
|
29.5 millimeter (mm)
Standard Deviation 26.12
|
|
Palatability Score
Acceptable to swallow:Day1:2-5min after medication
|
80.7 millimeter (mm)
Standard Deviation 17.57
|
59.2 millimeter (mm)
Standard Deviation 27.65
|
82.5 millimeter (mm)
Standard Deviation 23.04
|
68.7 millimeter (mm)
Standard Deviation 21.28
|
70.0 millimeter (mm)
Standard Deviation 19.50
|
38.1 millimeter (mm)
Standard Deviation 29.90
|
SECONDARY outcome
Timeframe: From the first dose of study drug administration up to 3-10 days after the last dose of the study drug (up to a maximum of 7 weeks)Population: The safety analysis set consisted of all subjects who received at least one dose of the trial medication and who had follow-up safety assessments.
Any clinically significant changes in laboratory evaluations ECGs,physical examination (body weight) and vital signs (temperature, blood pressure, pulse rate) were recorded as treatment emergent adverse events. Following parameters were analyzed for laboratory examination: hematology (haemoglobin, hematocrit, red blood cell count, mean cell hemoglobin \[MCH\], MCH concentration, mean cell volume, white cell count, platelets, neutrophils, lymphocytes, monocytes, eosinophils, Basophils); serum chemistry (sodium, potassium, calcium, inorganic phosphate, creatinine, total protein, albumin, urea, uric acid, aspartate aminotransferase \[AST\], alanine aminotransferase \[ALT\] gamma glutamyl transpeptidase, total bilirubin, alkaline phosphatase, glucose, triglycerides cholesterol); urinalysis (protein, glucose, ketones, pH, blood, leukocytes, nitrite); The 12-lead ECGs were recorded after the subjects had rested for at least 5 minutes in supine position.
Outcome measures
| Measure |
Treatment A
n=36 Participants
Subjects received a single oral dose of MSC2499550A formulation at 20 milligram per kilogram (mg/kg) dispersed in water under fed condition in one of the intervention periods. There was a wash-out period of at least 7 days between each intervention period.
|
Treatment B
n=36 Participants
Subjects received a single oral dose of current PZQ formulation (Cysticide®) at 40 mg/kg with water, under fed condition in one of the intervention periods. There was a wash-out period of at least 7 days between each of the intervention period.
|
Treatment C1
n=18 Participants
Subjects received a single oral dose of MSC2499550A formulation at 10 mg/kg dispersed in water under fed condition in one of the intervention periods. There was a wash-out period of at least 7 days between each of the intervention period.
|
Treatment C2
n=17 Participants
Subjects received a single oral dose of MSC2499550A formulation at 30 mg/kg dispersed in water under fed condition in one of the intervention periods. There was a wash-out period of at least 7 days between each of the intervention period.
|
Treatment D
n=35 Participants
Subjects received a single oral dose of MSC2499550A formulation at 20 mg/kg dispersed in water in fasted condition in one of the intervention periods. There was a wash-out period of at least 7 days between each of the intervention period.
|
Treatment E
n=36 Participants
Subjects received a single oral dose of MSC2499550A formulation at 20 mg/kg directly disintegrated in the mouth without water under fed conditions in one of the intervention periods. There was a wash-out period of at least 7 days between each of the intervention period.
|
|---|---|---|---|---|---|---|
|
Number of Subjects With Clinical Significant Laboratory Abnormalities, Electrocardiogram (ECG), Physical Examination and Vital Signs Reported as Treatment Emergent Adverse Events
Laboratory abnormalities
|
0 Subjects
|
0 Subjects
|
0 Subjects
|
0 Subjects
|
0 Subjects
|
0 Subjects
|
|
Number of Subjects With Clinical Significant Laboratory Abnormalities, Electrocardiogram (ECG), Physical Examination and Vital Signs Reported as Treatment Emergent Adverse Events
ECG abnormalities
|
0 Subjects
|
0 Subjects
|
0 Subjects
|
0 Subjects
|
0 Subjects
|
0 Subjects
|
|
Number of Subjects With Clinical Significant Laboratory Abnormalities, Electrocardiogram (ECG), Physical Examination and Vital Signs Reported as Treatment Emergent Adverse Events
Vital signs abnormalities
|
0 Subjects
|
0 Subjects
|
0 Subjects
|
0 Subjects
|
0 Subjects
|
0 Subjects
|
|
Number of Subjects With Clinical Significant Laboratory Abnormalities, Electrocardiogram (ECG), Physical Examination and Vital Signs Reported as Treatment Emergent Adverse Events
Physical signs abnormalities
|
0 Subjects
|
0 Subjects
|
0 Subjects
|
0 Subjects
|
0 Subjects
|
0 Subjects
|
Adverse Events
Treatment A
Serious events: 0 serious events
Other events: 8 other events
Deaths: 0 deaths
Treatment B
Serious events: 0 serious events
Other events: 17 other events
Deaths: 0 deaths
Treatment C1
Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths
Treatment C2
Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths
Treatment D
Serious events: 0 serious events
Other events: 5 other events
Deaths: 0 deaths
Treatment E
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Treatment A
n=36 participants at risk
Subjects received a single oral dose of MSC2499550A formulation at 20 milligram per kilogram (mg/kg) dispersed in water under fed condition in one of the intervention periods. There was a wash-out period of at least 7 days between each intervention period.
|
Treatment B
n=36 participants at risk
Subjects received a single oral dose of current PZQ formulation (Cysticide®) at 40 mg/kg with water, under fed condition in one of the intervention periods. There was a wash-out period of at least 7 days between each of the intervention period.
|
Treatment C1
n=18 participants at risk
Subjects received a single oral dose of MSC2499550A formulation at 10 mg/kg dispersed in water under fed condition in one of the intervention periods. There was a wash-out period of at least 7 days between each of the intervention period.
|
Treatment C2
n=17 participants at risk
Subjects received a single oral dose of MSC2499550A formulation at 30 mg/kg dispersed in water under fed condition in one of the intervention periods. There was a wash-out period of at least 7 days between each of the intervention period.
|
Treatment D
n=35 participants at risk
Subjects received a single oral dose of MSC2499550A formulation at 20 mg/kg dispersed in water in fasted condition in one of the intervention periods. There was a wash-out period of at least 7 days between each of the intervention period.
|
Treatment E
n=36 participants at risk
Subjects received a single oral dose of MSC2499550A formulation at 20 mg/kg directly disintegrated in the mouth without water under fed conditions in one of the intervention periods. There was a wash-out period of at least 7 days between each of the intervention period.
|
|---|---|---|---|---|---|---|
|
Gastrointestinal disorders
Diarrhoea
|
2.8%
1/36
|
0.00%
0/36
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/35
|
0.00%
0/36
|
|
Gastrointestinal disorders
Abdominal Discomfort
|
0.00%
0/36
|
2.8%
1/36
|
5.6%
1/18
|
0.00%
0/17
|
0.00%
0/35
|
0.00%
0/36
|
|
Gastrointestinal disorders
Abdominal Pain
|
0.00%
0/36
|
0.00%
0/36
|
0.00%
0/18
|
0.00%
0/17
|
2.9%
1/35
|
0.00%
0/36
|
|
Gastrointestinal disorders
Abdominal Pain Upper
|
0.00%
0/36
|
2.8%
1/36
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/35
|
0.00%
0/36
|
|
Gastrointestinal disorders
Dyspepsia
|
2.8%
1/36
|
0.00%
0/36
|
0.00%
0/18
|
5.9%
1/17
|
2.9%
1/35
|
2.8%
1/36
|
|
Gastrointestinal disorders
Nausea
|
2.8%
1/36
|
13.9%
5/36
|
0.00%
0/18
|
5.9%
1/17
|
0.00%
0/35
|
0.00%
0/36
|
|
Gastrointestinal disorders
Vomiting
|
2.8%
1/36
|
2.8%
1/36
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/35
|
0.00%
0/36
|
|
General disorders
Fatigue
|
2.8%
1/36
|
0.00%
0/36
|
5.6%
1/18
|
0.00%
0/17
|
0.00%
0/35
|
0.00%
0/36
|
|
Infections and infestations
Influenza
|
0.00%
0/36
|
0.00%
0/36
|
5.6%
1/18
|
0.00%
0/17
|
0.00%
0/35
|
0.00%
0/36
|
|
Infections and infestations
Tonsillitis
|
0.00%
0/36
|
0.00%
0/36
|
5.6%
1/18
|
0.00%
0/17
|
0.00%
0/35
|
0.00%
0/36
|
|
Injury, poisoning and procedural complications
Excoriation
|
0.00%
0/36
|
0.00%
0/36
|
0.00%
0/18
|
5.9%
1/17
|
0.00%
0/35
|
0.00%
0/36
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal Pain
|
2.8%
1/36
|
0.00%
0/36
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/35
|
0.00%
0/36
|
|
Nervous system disorders
Dizziness
|
0.00%
0/36
|
2.8%
1/36
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/35
|
0.00%
0/36
|
|
Nervous system disorders
Dysgeusia
|
0.00%
0/36
|
2.8%
1/36
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/35
|
0.00%
0/36
|
|
Nervous system disorders
Headache
|
16.7%
6/36
|
30.6%
11/36
|
0.00%
0/18
|
11.8%
2/17
|
14.3%
5/35
|
0.00%
0/36
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal Pain
|
0.00%
0/36
|
0.00%
0/36
|
5.6%
1/18
|
0.00%
0/17
|
0.00%
0/35
|
0.00%
0/36
|
Additional Information
Merck KGaA Communication Center
Merck Healthcare, a business of Merck KGaA, Darmstadt, Germany
Phone: +49-6151-72-5200
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: OTHER