Trial Outcomes & Findings for A Study to Assess the Relative Bioavailability of Process Variants of Selumetinib in Healthy Male Volunteers (NCT NCT02322749)
NCT ID: NCT02322749
Last Updated: 2016-08-31
Results Overview
The bioequivalence of the free base variant of selumetinib (Treatment B) as compared to the blue reference capsule (Treatment A) was evaluated by comparing the maximum observed plasma concentration (Cmax) of selumetinib in healthy volunteers.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
48 participants
Primary outcome timeframe
Blood samples were collected pre-dose, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 4, 6, 8, 12, 24, 36 and 48 hours post dose for each of the separate treatment periods (Visits 2, 3 and 4).
Results posted on
2016-08-31
Participant Flow
48 healthy adult males were enrolled in this single centre, randomised, open label, 3-period, 3-treatment and 6-sequence crossover study from 24 February 2015 to study completion on 30 April 2015. Subjects attended the clinical study unit for at least 1 screening visit and 3 treatment periods.
48 subjects received at least 1 of the 3 treatments and 45 completed all 3 treatment periods. There was a washout period of 7 to 10 days between administrations. A follow-up visit occurred 7 days after the last administration of the third treatment period.
Participant milestones
| Measure |
Sequence ABC
Subjects randomized to treatment sequences ABC: A=Selumetinib Blue Reference Capsules; B=Selumetinib Blue Free Base Variant Capsules; C=Selumetinib Blue TPGS Variant Capsules. Subjects received 75 mg selumetinib (3 x 25 mg capsules) administered as a single oral dose on Day 1 of each period according to their treatment sequence under fasted conditions (10 hours prior to administration) in a crossover fashion. There was a washout period of 7-10 days between administrations.
|
Sequence ACB
Subjects randomized to treatment sequences ACB: A=Selumetinib Blue Reference Capsules; C=Selumetinib Blue TPGS Variant Capsules; B=Selumetinib Blue Free Base Variant Capsules. Subjects received 75 mg selumetinib (3 x 25 mg capsules) administered as a single oral dose on Day 1 of each period according to their treatment sequence under fasted conditions (10 hours prior to administration) in a crossover fashion. There was a washout period of 7-10 days between administrations.
|
Sequence BAC
Subjects randomized to treatment sequences BAC: B=Selumetinib Blue Free Base Variant Capsules; A=Selumetinib Blue Reference Capsules; C=Selumetinib Blue TPGS Variant Capsules. Subjects received 75 mg selumetinib (3 x 25 mg capsules) administered as a single oral dose on Day 1 of each period according to their treatment sequence under fasted conditions (10 hours prior to administration) in a crossover fashion. There was a washout period of 7-10 days between administrations.
|
Sequence BCA
Subjects randomized to treatment sequences BCA: B=Selumetinib Blue Free Base Variant Capsules; C=Selumetinib Blue TPGS Variant Capsules; A=Selumetinib Blue Reference Capsules. Subjects received 75 mg selumetinib (3 x 25 mg capsules) administered as a single oral dose on Day 1 of each period according to their treatment sequence under fasted conditions (10 hours prior to administration) in a crossover fashion. There was a washout period of 7-10 days between administrations.
|
Sequence CAB
Subjects randomized to treatment sequences CAB: C=Selumetinib Blue TPGS Variant Capsules; A=Selumetinib Blue Reference Capsules; B=Selumetinib Blue Free Base Variant Capsules. Subjects received 75 mg selumetinib (3 x 25 mg capsules) administered as a single oral dose on Day 1 of each period according to their treatment sequence under fasted conditions (10 hours prior to administration) in a crossover fashion. There was a washout period of 7-10 days between administrations.
|
Sequence CBA
Subjects randomized to treatment sequences CBA: C=Selumetinib Blue TPGS Variant Capsules; B=Selumetinib Blue Free Base Variant Capsules; A=Selumetinib Blue Reference Capsules. Subjects received 75 mg selumetinib (3 x 25 mg capsules) administered as a single oral dose on Day 1 of each period according to their treatment sequence under fasted conditions (10 hours prior to administration) in a crossover fashion. There was a washout period of 7-10 days between administrations.
|
|---|---|---|---|---|---|---|
|
Period 1
STARTED
|
8
|
8
|
8
|
8
|
8
|
8
|
|
Period 1
COMPLETED
|
8
|
8
|
8
|
8
|
8
|
8
|
|
Period 1
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Period 2
STARTED
|
8
|
8
|
8
|
8
|
8
|
8
|
|
Period 2
COMPLETED
|
8
|
8
|
8
|
6
|
8
|
8
|
|
Period 2
NOT COMPLETED
|
0
|
0
|
0
|
2
|
0
|
0
|
|
Period 3
STARTED
|
8
|
8
|
8
|
6
|
8
|
8
|
|
Period 3
COMPLETED
|
8
|
8
|
7
|
6
|
8
|
8
|
|
Period 3
NOT COMPLETED
|
0
|
0
|
1
|
0
|
0
|
0
|
Reasons for withdrawal
| Measure |
Sequence ABC
Subjects randomized to treatment sequences ABC: A=Selumetinib Blue Reference Capsules; B=Selumetinib Blue Free Base Variant Capsules; C=Selumetinib Blue TPGS Variant Capsules. Subjects received 75 mg selumetinib (3 x 25 mg capsules) administered as a single oral dose on Day 1 of each period according to their treatment sequence under fasted conditions (10 hours prior to administration) in a crossover fashion. There was a washout period of 7-10 days between administrations.
|
Sequence ACB
Subjects randomized to treatment sequences ACB: A=Selumetinib Blue Reference Capsules; C=Selumetinib Blue TPGS Variant Capsules; B=Selumetinib Blue Free Base Variant Capsules. Subjects received 75 mg selumetinib (3 x 25 mg capsules) administered as a single oral dose on Day 1 of each period according to their treatment sequence under fasted conditions (10 hours prior to administration) in a crossover fashion. There was a washout period of 7-10 days between administrations.
|
Sequence BAC
Subjects randomized to treatment sequences BAC: B=Selumetinib Blue Free Base Variant Capsules; A=Selumetinib Blue Reference Capsules; C=Selumetinib Blue TPGS Variant Capsules. Subjects received 75 mg selumetinib (3 x 25 mg capsules) administered as a single oral dose on Day 1 of each period according to their treatment sequence under fasted conditions (10 hours prior to administration) in a crossover fashion. There was a washout period of 7-10 days between administrations.
|
Sequence BCA
Subjects randomized to treatment sequences BCA: B=Selumetinib Blue Free Base Variant Capsules; C=Selumetinib Blue TPGS Variant Capsules; A=Selumetinib Blue Reference Capsules. Subjects received 75 mg selumetinib (3 x 25 mg capsules) administered as a single oral dose on Day 1 of each period according to their treatment sequence under fasted conditions (10 hours prior to administration) in a crossover fashion. There was a washout period of 7-10 days between administrations.
|
Sequence CAB
Subjects randomized to treatment sequences CAB: C=Selumetinib Blue TPGS Variant Capsules; A=Selumetinib Blue Reference Capsules; B=Selumetinib Blue Free Base Variant Capsules. Subjects received 75 mg selumetinib (3 x 25 mg capsules) administered as a single oral dose on Day 1 of each period according to their treatment sequence under fasted conditions (10 hours prior to administration) in a crossover fashion. There was a washout period of 7-10 days between administrations.
|
Sequence CBA
Subjects randomized to treatment sequences CBA: C=Selumetinib Blue TPGS Variant Capsules; B=Selumetinib Blue Free Base Variant Capsules; A=Selumetinib Blue Reference Capsules. Subjects received 75 mg selumetinib (3 x 25 mg capsules) administered as a single oral dose on Day 1 of each period according to their treatment sequence under fasted conditions (10 hours prior to administration) in a crossover fashion. There was a washout period of 7-10 days between administrations.
|
|---|---|---|---|---|---|---|
|
Period 2
Adverse Event
|
0
|
0
|
0
|
1
|
0
|
0
|
|
Period 2
Withdrawal by Subject
|
0
|
0
|
0
|
1
|
0
|
0
|
|
Period 3
Withdrawal by Subject
|
0
|
0
|
1
|
0
|
0
|
0
|
Baseline Characteristics
A Study to Assess the Relative Bioavailability of Process Variants of Selumetinib in Healthy Male Volunteers
Baseline characteristics by cohort
| Measure |
Overall Study
n=48 Participants
All subjects received at least 1 dose of selumetinib. Subjects were randomised in a crossover fashion to receive 1 of 3 treatments during each treatment period: Period 1=Visit 2; Period 2=Visit 3; Period 3=Visit 4.
|
|---|---|
|
Age, Continuous
|
31 years
STANDARD_DEVIATION 8 • n=99 Participants
|
|
Sex: Female, Male
Female
|
0 Participants
n=99 Participants
|
|
Sex: Female, Male
Male
|
48 Participants
n=99 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=99 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=99 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=99 Participants
|
|
Race (NIH/OMB)
Black or African American
|
8 Participants
n=99 Participants
|
|
Race (NIH/OMB)
White
|
40 Participants
n=99 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=99 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=99 Participants
|
PRIMARY outcome
Timeframe: Blood samples were collected pre-dose, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 4, 6, 8, 12, 24, 36 and 48 hours post dose for each of the separate treatment periods (Visits 2, 3 and 4).Population: The Pharmacokinetic (PK) analysis set included all healthy subjects who received at least 1 dose of selumetinib and had at least 1 post-dose PK measurement without important protocol deviations/violations or events significantly affecting the PK.
The bioequivalence of the free base variant of selumetinib (Treatment B) as compared to the blue reference capsule (Treatment A) was evaluated by comparing the maximum observed plasma concentration (Cmax) of selumetinib in healthy volunteers.
Outcome measures
| Measure |
Treatment A: Selumetinib Blue Reference Capsules
n=46 Participants
Subjects received 75 mg selumetinib (3 x 25 mg blue reference capsules) administered as a single oral dose on Day 1 of each period according to their treatment sequence under fasted conditions (10 hours prior to administration).
|
Treatment B: Selumetinib Blue Free Base Variant Capsules
n=48 Participants
Subjects received 75 mg selumetinib (3 x 25 mg free base variant capsules) administered as a single oral dose on Day 1 of each period according to their treatment sequence under fasted conditions (10 hours prior to administration).
|
Treatment C: Selumetinib Blue TPGS Variant Capsules
Subjects received 75 mg selumetinib (3 x 25 mg vitamin E polyethylene glycol succinate \[TPGS\] variant capsules) administered as a single oral dose on Day 1 of each period according to their treatment sequence under fasted conditions (10 hours prior to administration).
|
|---|---|---|---|
|
Bioequivalence of the Free Base Variant of Selumetinib (Treatment B) Compared to the Blue Reference Capsule (Treatment A) [Selumetinib Cmax]
|
1330 nanograms per millilitre (ng/mL)
Geometric Coefficient of Variation 36.6
|
124 nanograms per millilitre (ng/mL)
Geometric Coefficient of Variation 50.3
|
—
|
PRIMARY outcome
Timeframe: Blood samples were collected pre-dose, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 4, 6, 8, 12, 24, 36 and 48 hours post dose for each of the separate treatment periods (Visits 2, 3 and 4).Population: The PK analysis set included all healthy subjects who received at least 1 dose of selumetinib and had at least 1 post-dose PK measurement without important protocol deviations/violations or events significantly affecting the PK.
The bioequivalence of the free base variant of selumetinib (Treatment B) as compared to the blue reference capsule (Treatment A) was evaluated by comparing the area under the plasma concentration-time curve from time zero extrapolated to infinity (AUC) of selumetinib in healthy volunteers.
Outcome measures
| Measure |
Treatment A: Selumetinib Blue Reference Capsules
n=45 Participants
Subjects received 75 mg selumetinib (3 x 25 mg blue reference capsules) administered as a single oral dose on Day 1 of each period according to their treatment sequence under fasted conditions (10 hours prior to administration).
|
Treatment B: Selumetinib Blue Free Base Variant Capsules
n=41 Participants
Subjects received 75 mg selumetinib (3 x 25 mg free base variant capsules) administered as a single oral dose on Day 1 of each period according to their treatment sequence under fasted conditions (10 hours prior to administration).
|
Treatment C: Selumetinib Blue TPGS Variant Capsules
Subjects received 75 mg selumetinib (3 x 25 mg vitamin E polyethylene glycol succinate \[TPGS\] variant capsules) administered as a single oral dose on Day 1 of each period according to their treatment sequence under fasted conditions (10 hours prior to administration).
|
|---|---|---|---|
|
Bioequivalence of the Free Base Variant of Selumetinib (Treatment B) Compared to the Blue Reference Capsule (Treatment A) [Selumetinib AUC]
|
3750 ng * hour per mL (ng*h/mL)
Geometric Coefficient of Variation 24.1
|
905 ng * hour per mL (ng*h/mL)
Geometric Coefficient of Variation 32.6
|
—
|
PRIMARY outcome
Timeframe: Blood samples were collected pre-dose, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 4, 6, 8, 12, 24, 36 and 48 hours post dose for each of the separate treatment periods (Visits 2, 3 and 4).Population: The PK analysis set included all healthy subjects who received at least 1 dose of selumetinib and had at least 1 post-dose PK measurement without important protocol deviations/violations or events significantly affecting the PK.
The bioequivalence of the free base variant of selumetinib (Treatment B) as compared to the blue reference capsule (Treatment A) was evaluated by comparing the AUC from time zero to the time of the last quantifiable concentration (AUC\[0-t\]) of selumetinib in healthy volunteers.
Outcome measures
| Measure |
Treatment A: Selumetinib Blue Reference Capsules
n=45 Participants
Subjects received 75 mg selumetinib (3 x 25 mg blue reference capsules) administered as a single oral dose on Day 1 of each period according to their treatment sequence under fasted conditions (10 hours prior to administration).
|
Treatment B: Selumetinib Blue Free Base Variant Capsules
n=48 Participants
Subjects received 75 mg selumetinib (3 x 25 mg free base variant capsules) administered as a single oral dose on Day 1 of each period according to their treatment sequence under fasted conditions (10 hours prior to administration).
|
Treatment C: Selumetinib Blue TPGS Variant Capsules
Subjects received 75 mg selumetinib (3 x 25 mg vitamin E polyethylene glycol succinate \[TPGS\] variant capsules) administered as a single oral dose on Day 1 of each period according to their treatment sequence under fasted conditions (10 hours prior to administration).
|
|---|---|---|---|
|
Bioequivalence of the Free Base Variant of Selumetinib (Treatment B) Compared to the Blue Reference Capsule (Treatment A) [Selumetinib AUC(0-t)]
|
3670 ng*h/mL
Geometric Coefficient of Variation 24.0
|
814 ng*h/mL
Geometric Coefficient of Variation 32.2
|
—
|
SECONDARY outcome
Timeframe: Blood samples were collected pre-dose, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 4, 6, 8, 12, 24, 36 and 48 hours post-dose for each of the separate treatment periods (Visits 2, 3 and 4).Population: The PK analysis set included all healthy subjects who received at least 1 dose of selumetinib and had at least 1 post-dose PK measurement without important protocol deviations/violations or events significantly affecting the PK.
The relative bioavailability of the TPGS capsule variant of selumetinib (Treatment C) as compared to the blue reference capsule (Treatment A) was evaluated by comparing the Cmax of selumetinib in healthy volunteers.
Outcome measures
| Measure |
Treatment A: Selumetinib Blue Reference Capsules
n=46 Participants
Subjects received 75 mg selumetinib (3 x 25 mg blue reference capsules) administered as a single oral dose on Day 1 of each period according to their treatment sequence under fasted conditions (10 hours prior to administration).
|
Treatment B: Selumetinib Blue Free Base Variant Capsules
n=44 Participants
Subjects received 75 mg selumetinib (3 x 25 mg free base variant capsules) administered as a single oral dose on Day 1 of each period according to their treatment sequence under fasted conditions (10 hours prior to administration).
|
Treatment C: Selumetinib Blue TPGS Variant Capsules
Subjects received 75 mg selumetinib (3 x 25 mg vitamin E polyethylene glycol succinate \[TPGS\] variant capsules) administered as a single oral dose on Day 1 of each period according to their treatment sequence under fasted conditions (10 hours prior to administration).
|
|---|---|---|---|
|
Relative Bioavailability of the TPGS Capsule Variant (Treatment C) Compared to the Blue Reference Capsule (Treatment A) [Selumetinib Cmax]
|
1330 ng/mL
Geometric Coefficient of Variation 36.6
|
172 ng/mL
Geometric Coefficient of Variation 46.5
|
—
|
SECONDARY outcome
Timeframe: Blood samples were collected pre-dose, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 4, 6, 8, 12, 24, 36 and 48 hours post-dose for each of the separate treatment periods (Visits 2, 3 and 4).Population: The PK analysis set included all healthy subjects who received at least 1 dose of selumetinib and had at least 1 post-dose PK measurement without important protocol deviations/violations or events significantly affecting the PK.
The relative bioavailability of the TPGS capsules variant of selumetinib (Treatment C) as compared to the blue reference capsule (Treatment A) was evaluated by comparing the AUC of selumetinib in healthy volunteers.
Outcome measures
| Measure |
Treatment A: Selumetinib Blue Reference Capsules
n=45 Participants
Subjects received 75 mg selumetinib (3 x 25 mg blue reference capsules) administered as a single oral dose on Day 1 of each period according to their treatment sequence under fasted conditions (10 hours prior to administration).
|
Treatment B: Selumetinib Blue Free Base Variant Capsules
n=40 Participants
Subjects received 75 mg selumetinib (3 x 25 mg free base variant capsules) administered as a single oral dose on Day 1 of each period according to their treatment sequence under fasted conditions (10 hours prior to administration).
|
Treatment C: Selumetinib Blue TPGS Variant Capsules
Subjects received 75 mg selumetinib (3 x 25 mg vitamin E polyethylene glycol succinate \[TPGS\] variant capsules) administered as a single oral dose on Day 1 of each period according to their treatment sequence under fasted conditions (10 hours prior to administration).
|
|---|---|---|---|
|
Relative Bioavailability of the TPGS Capsule Variant (Treatment C) Compared to the Blue Reference Capsule (Treatment A) [Selumetinib AUC]
|
3750 ng*h/mL
Geometric Coefficient of Variation 24.1
|
975 ng*h/mL
Geometric Coefficient of Variation 31.7
|
—
|
SECONDARY outcome
Timeframe: Blood samples were collected pre-dose, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 4, 6, 8, 12, 24, 36 and 48 hours post-dose for each of the separate treatment periods (Visits 2, 3 and 4).Population: The PK analysis set included all healthy subjects who received at least 1 dose of selumetinib and had at least 1 post-dose PK measurement without important protocol deviations/violations or events significantly affecting the PK.
The relative bioavailability of the TPGS capsule variant of selumetinib (Treatment C) as compared to the blue reference capsule (Treatment A) was evaluated by comparing the AUC\[0-t\] of selumetinib in healthy volunteers.
Outcome measures
| Measure |
Treatment A: Selumetinib Blue Reference Capsules
n=45 Participants
Subjects received 75 mg selumetinib (3 x 25 mg blue reference capsules) administered as a single oral dose on Day 1 of each period according to their treatment sequence under fasted conditions (10 hours prior to administration).
|
Treatment B: Selumetinib Blue Free Base Variant Capsules
n=44 Participants
Subjects received 75 mg selumetinib (3 x 25 mg free base variant capsules) administered as a single oral dose on Day 1 of each period according to their treatment sequence under fasted conditions (10 hours prior to administration).
|
Treatment C: Selumetinib Blue TPGS Variant Capsules
Subjects received 75 mg selumetinib (3 x 25 mg vitamin E polyethylene glycol succinate \[TPGS\] variant capsules) administered as a single oral dose on Day 1 of each period according to their treatment sequence under fasted conditions (10 hours prior to administration).
|
|---|---|---|---|
|
Relative Bioavailability of the TPGS Capsule Variant (Treatment C) Compared to the Blue Reference Capsule (Treatment A) [Selumetinib AUC(0-t)]
|
3670 ng*h/mL
Geometric Coefficient of Variation 24.0
|
866 ng*h/mL
Geometric Coefficient of Variation 31.4
|
—
|
SECONDARY outcome
Timeframe: Blood samples were collected pre-dose, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 4, 6, 8, 12, 24, 36 and 48 hours post-dose for each of the separate treatment periods (Visits 2, 3 and 4).Population: The PK analysis set included all healthy subjects who received at least 1 dose of selumetinib and had at least 1 post-dose PK measurement without important protocol deviations/violations or events significantly affecting the PK.
The PK of the metabolite N-desmethyl selumetinib was evaluated by assessing the Cmax of the metabolite in healthy volunteers after oral administration of single doses of the blue reference capsule (Treatment A), the free base variant capsule (Treatment B) and the TPGS variant capsule (Treatment C).
Outcome measures
| Measure |
Treatment A: Selumetinib Blue Reference Capsules
n=46 Participants
Subjects received 75 mg selumetinib (3 x 25 mg blue reference capsules) administered as a single oral dose on Day 1 of each period according to their treatment sequence under fasted conditions (10 hours prior to administration).
|
Treatment B: Selumetinib Blue Free Base Variant Capsules
n=48 Participants
Subjects received 75 mg selumetinib (3 x 25 mg free base variant capsules) administered as a single oral dose on Day 1 of each period according to their treatment sequence under fasted conditions (10 hours prior to administration).
|
Treatment C: Selumetinib Blue TPGS Variant Capsules
n=44 Participants
Subjects received 75 mg selumetinib (3 x 25 mg vitamin E polyethylene glycol succinate \[TPGS\] variant capsules) administered as a single oral dose on Day 1 of each period according to their treatment sequence under fasted conditions (10 hours prior to administration).
|
|---|---|---|---|
|
The PK of the Metabolite N-desmethyl Selumetinib by Assessment of Cmax
|
95.2 ng/mL
Geometric Coefficient of Variation 34.8
|
9.13 ng/mL
Geometric Coefficient of Variation 50.9
|
12.3 ng/mL
Geometric Coefficient of Variation 48.6
|
SECONDARY outcome
Timeframe: Blood samples were collected pre-dose, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 4, 6, 8, 12, 24, 36 and 48 hours post-dose for each of the separate treatment periods (Visits 2, 3 and 4).Population: The PK analysis set included all healthy subjects who received at least 1 dose of selumetinib and had at least 1 post-dose PK measurement without important protocol deviations/violations or events significantly affecting the PK.
The PK of the metabolite N-desmethyl selumetinib was evaluated by assessing the AUC(0-t) of the metabolite in healthy volunteers after oral administration of single doses of the blue reference capsule (Treatment A), the free base variant capsule (Treatment B) and the TPGS variant capsule (Treatment C).
Outcome measures
| Measure |
Treatment A: Selumetinib Blue Reference Capsules
n=45 Participants
Subjects received 75 mg selumetinib (3 x 25 mg blue reference capsules) administered as a single oral dose on Day 1 of each period according to their treatment sequence under fasted conditions (10 hours prior to administration).
|
Treatment B: Selumetinib Blue Free Base Variant Capsules
n=48 Participants
Subjects received 75 mg selumetinib (3 x 25 mg free base variant capsules) administered as a single oral dose on Day 1 of each period according to their treatment sequence under fasted conditions (10 hours prior to administration).
|
Treatment C: Selumetinib Blue TPGS Variant Capsules
n=44 Participants
Subjects received 75 mg selumetinib (3 x 25 mg vitamin E polyethylene glycol succinate \[TPGS\] variant capsules) administered as a single oral dose on Day 1 of each period according to their treatment sequence under fasted conditions (10 hours prior to administration).
|
|---|---|---|---|
|
The PK of N-desmethyl Selumetinib by Assessment of the AUC(0-t)
|
267 ng*h/mL
Geometric Coefficient of Variation 31.1
|
30.2 ng*h/mL
Geometric Coefficient of Variation 72.1
|
33.9 ng*h/mL
Geometric Coefficient of Variation 66.2
|
Adverse Events
Treatment A: Selumetinib Blue Reference Capsules
Serious events: 0 serious events
Other events: 12 other events
Deaths: 0 deaths
Treatment B: Selumetinib Blue Free Base Variant Capsules
Serious events: 0 serious events
Other events: 12 other events
Deaths: 0 deaths
Treatment C: Selumetinib Blue TPGS Variant Capsules
Serious events: 0 serious events
Other events: 9 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Treatment A: Selumetinib Blue Reference Capsules
n=46 participants at risk
Subjects received 75 mg selumetinib (3 x 25 mg blue reference capsules) administered as a single oral dose on Day 1 of each period according to their treatment sequence under fasted conditions (10 hours prior to administration).
|
Treatment B: Selumetinib Blue Free Base Variant Capsules
n=48 participants at risk
Subjects received 75 mg selumetinib (3 x 25 mg free base variant capsules) administered as a single oral dose on Day 1 of each period according to their treatment sequence under fasted conditions (10 hours prior to administration).
|
Treatment C: Selumetinib Blue TPGS Variant Capsules
n=45 participants at risk
Subjects received 75 mg selumetinib (3 x 25 mg vitamin E polyethylene glycol succinate \[TPGS\] variant capsules) administered as a single oral dose on Day 1 of each period according to their treatment sequence under fasted conditions (10 hours prior to administration).
|
|---|---|---|---|
|
Eye disorders
Blepharospasm
|
2.2%
1/46 • Number of events 1 • All adverse events (AEs) were collected from randomisation (Visit 2, Day 1) until the follow-up visit (Visit 5).
Visits 2, 3 and 4 comprised 3 separate treatment periods with a washout period of 7 - 10 days between administrations.
|
0.00%
0/48 • All adverse events (AEs) were collected from randomisation (Visit 2, Day 1) until the follow-up visit (Visit 5).
Visits 2, 3 and 4 comprised 3 separate treatment periods with a washout period of 7 - 10 days between administrations.
|
0.00%
0/45 • All adverse events (AEs) were collected from randomisation (Visit 2, Day 1) until the follow-up visit (Visit 5).
Visits 2, 3 and 4 comprised 3 separate treatment periods with a washout period of 7 - 10 days between administrations.
|
|
Eye disorders
Eye Pruritus
|
0.00%
0/46 • All adverse events (AEs) were collected from randomisation (Visit 2, Day 1) until the follow-up visit (Visit 5).
Visits 2, 3 and 4 comprised 3 separate treatment periods with a washout period of 7 - 10 days between administrations.
|
0.00%
0/48 • All adverse events (AEs) were collected from randomisation (Visit 2, Day 1) until the follow-up visit (Visit 5).
Visits 2, 3 and 4 comprised 3 separate treatment periods with a washout period of 7 - 10 days between administrations.
|
2.2%
1/45 • Number of events 1 • All adverse events (AEs) were collected from randomisation (Visit 2, Day 1) until the follow-up visit (Visit 5).
Visits 2, 3 and 4 comprised 3 separate treatment periods with a washout period of 7 - 10 days between administrations.
|
|
Eye disorders
Ocular Hyperaemia
|
0.00%
0/46 • All adverse events (AEs) were collected from randomisation (Visit 2, Day 1) until the follow-up visit (Visit 5).
Visits 2, 3 and 4 comprised 3 separate treatment periods with a washout period of 7 - 10 days between administrations.
|
2.1%
1/48 • Number of events 1 • All adverse events (AEs) were collected from randomisation (Visit 2, Day 1) until the follow-up visit (Visit 5).
Visits 2, 3 and 4 comprised 3 separate treatment periods with a washout period of 7 - 10 days between administrations.
|
0.00%
0/45 • All adverse events (AEs) were collected from randomisation (Visit 2, Day 1) until the follow-up visit (Visit 5).
Visits 2, 3 and 4 comprised 3 separate treatment periods with a washout period of 7 - 10 days between administrations.
|
|
Eye disorders
Vision Blurred
|
0.00%
0/46 • All adverse events (AEs) were collected from randomisation (Visit 2, Day 1) until the follow-up visit (Visit 5).
Visits 2, 3 and 4 comprised 3 separate treatment periods with a washout period of 7 - 10 days between administrations.
|
2.1%
1/48 • Number of events 1 • All adverse events (AEs) were collected from randomisation (Visit 2, Day 1) until the follow-up visit (Visit 5).
Visits 2, 3 and 4 comprised 3 separate treatment periods with a washout period of 7 - 10 days between administrations.
|
2.2%
1/45 • Number of events 1 • All adverse events (AEs) were collected from randomisation (Visit 2, Day 1) until the follow-up visit (Visit 5).
Visits 2, 3 and 4 comprised 3 separate treatment periods with a washout period of 7 - 10 days between administrations.
|
|
Gastrointestinal disorders
Abdominal Pain
|
0.00%
0/46 • All adverse events (AEs) were collected from randomisation (Visit 2, Day 1) until the follow-up visit (Visit 5).
Visits 2, 3 and 4 comprised 3 separate treatment periods with a washout period of 7 - 10 days between administrations.
|
2.1%
1/48 • Number of events 1 • All adverse events (AEs) were collected from randomisation (Visit 2, Day 1) until the follow-up visit (Visit 5).
Visits 2, 3 and 4 comprised 3 separate treatment periods with a washout period of 7 - 10 days between administrations.
|
0.00%
0/45 • All adverse events (AEs) were collected from randomisation (Visit 2, Day 1) until the follow-up visit (Visit 5).
Visits 2, 3 and 4 comprised 3 separate treatment periods with a washout period of 7 - 10 days between administrations.
|
|
Gastrointestinal disorders
Constipation
|
2.2%
1/46 • Number of events 1 • All adverse events (AEs) were collected from randomisation (Visit 2, Day 1) until the follow-up visit (Visit 5).
Visits 2, 3 and 4 comprised 3 separate treatment periods with a washout period of 7 - 10 days between administrations.
|
0.00%
0/48 • All adverse events (AEs) were collected from randomisation (Visit 2, Day 1) until the follow-up visit (Visit 5).
Visits 2, 3 and 4 comprised 3 separate treatment periods with a washout period of 7 - 10 days between administrations.
|
2.2%
1/45 • Number of events 1 • All adverse events (AEs) were collected from randomisation (Visit 2, Day 1) until the follow-up visit (Visit 5).
Visits 2, 3 and 4 comprised 3 separate treatment periods with a washout period of 7 - 10 days between administrations.
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/46 • All adverse events (AEs) were collected from randomisation (Visit 2, Day 1) until the follow-up visit (Visit 5).
Visits 2, 3 and 4 comprised 3 separate treatment periods with a washout period of 7 - 10 days between administrations.
|
2.1%
1/48 • Number of events 2 • All adverse events (AEs) were collected from randomisation (Visit 2, Day 1) until the follow-up visit (Visit 5).
Visits 2, 3 and 4 comprised 3 separate treatment periods with a washout period of 7 - 10 days between administrations.
|
0.00%
0/45 • All adverse events (AEs) were collected from randomisation (Visit 2, Day 1) until the follow-up visit (Visit 5).
Visits 2, 3 and 4 comprised 3 separate treatment periods with a washout period of 7 - 10 days between administrations.
|
|
Gastrointestinal disorders
Toothache
|
0.00%
0/46 • All adverse events (AEs) were collected from randomisation (Visit 2, Day 1) until the follow-up visit (Visit 5).
Visits 2, 3 and 4 comprised 3 separate treatment periods with a washout period of 7 - 10 days between administrations.
|
2.1%
1/48 • Number of events 1 • All adverse events (AEs) were collected from randomisation (Visit 2, Day 1) until the follow-up visit (Visit 5).
Visits 2, 3 and 4 comprised 3 separate treatment periods with a washout period of 7 - 10 days between administrations.
|
0.00%
0/45 • All adverse events (AEs) were collected from randomisation (Visit 2, Day 1) until the follow-up visit (Visit 5).
Visits 2, 3 and 4 comprised 3 separate treatment periods with a washout period of 7 - 10 days between administrations.
|
|
General disorders
Catheter Site Bruise
|
2.2%
1/46 • Number of events 1 • All adverse events (AEs) were collected from randomisation (Visit 2, Day 1) until the follow-up visit (Visit 5).
Visits 2, 3 and 4 comprised 3 separate treatment periods with a washout period of 7 - 10 days between administrations.
|
0.00%
0/48 • All adverse events (AEs) were collected from randomisation (Visit 2, Day 1) until the follow-up visit (Visit 5).
Visits 2, 3 and 4 comprised 3 separate treatment periods with a washout period of 7 - 10 days between administrations.
|
0.00%
0/45 • All adverse events (AEs) were collected from randomisation (Visit 2, Day 1) until the follow-up visit (Visit 5).
Visits 2, 3 and 4 comprised 3 separate treatment periods with a washout period of 7 - 10 days between administrations.
|
|
General disorders
Catheter Site Pain
|
0.00%
0/46 • All adverse events (AEs) were collected from randomisation (Visit 2, Day 1) until the follow-up visit (Visit 5).
Visits 2, 3 and 4 comprised 3 separate treatment periods with a washout period of 7 - 10 days between administrations.
|
0.00%
0/48 • All adverse events (AEs) were collected from randomisation (Visit 2, Day 1) until the follow-up visit (Visit 5).
Visits 2, 3 and 4 comprised 3 separate treatment periods with a washout period of 7 - 10 days between administrations.
|
2.2%
1/45 • Number of events 1 • All adverse events (AEs) were collected from randomisation (Visit 2, Day 1) until the follow-up visit (Visit 5).
Visits 2, 3 and 4 comprised 3 separate treatment periods with a washout period of 7 - 10 days between administrations.
|
|
General disorders
Catheter Site Related Reaction
|
0.00%
0/46 • All adverse events (AEs) were collected from randomisation (Visit 2, Day 1) until the follow-up visit (Visit 5).
Visits 2, 3 and 4 comprised 3 separate treatment periods with a washout period of 7 - 10 days between administrations.
|
0.00%
0/48 • All adverse events (AEs) were collected from randomisation (Visit 2, Day 1) until the follow-up visit (Visit 5).
Visits 2, 3 and 4 comprised 3 separate treatment periods with a washout period of 7 - 10 days between administrations.
|
2.2%
1/45 • Number of events 1 • All adverse events (AEs) were collected from randomisation (Visit 2, Day 1) until the follow-up visit (Visit 5).
Visits 2, 3 and 4 comprised 3 separate treatment periods with a washout period of 7 - 10 days between administrations.
|
|
Infections and infestations
Rhinitis
|
2.2%
1/46 • Number of events 1 • All adverse events (AEs) were collected from randomisation (Visit 2, Day 1) until the follow-up visit (Visit 5).
Visits 2, 3 and 4 comprised 3 separate treatment periods with a washout period of 7 - 10 days between administrations.
|
0.00%
0/48 • All adverse events (AEs) were collected from randomisation (Visit 2, Day 1) until the follow-up visit (Visit 5).
Visits 2, 3 and 4 comprised 3 separate treatment periods with a washout period of 7 - 10 days between administrations.
|
2.2%
1/45 • Number of events 1 • All adverse events (AEs) were collected from randomisation (Visit 2, Day 1) until the follow-up visit (Visit 5).
Visits 2, 3 and 4 comprised 3 separate treatment periods with a washout period of 7 - 10 days between administrations.
|
|
Injury, poisoning and procedural complications
Muscle Strain
|
2.2%
1/46 • Number of events 1 • All adverse events (AEs) were collected from randomisation (Visit 2, Day 1) until the follow-up visit (Visit 5).
Visits 2, 3 and 4 comprised 3 separate treatment periods with a washout period of 7 - 10 days between administrations.
|
0.00%
0/48 • All adverse events (AEs) were collected from randomisation (Visit 2, Day 1) until the follow-up visit (Visit 5).
Visits 2, 3 and 4 comprised 3 separate treatment periods with a washout period of 7 - 10 days between administrations.
|
0.00%
0/45 • All adverse events (AEs) were collected from randomisation (Visit 2, Day 1) until the follow-up visit (Visit 5).
Visits 2, 3 and 4 comprised 3 separate treatment periods with a washout period of 7 - 10 days between administrations.
|
|
Injury, poisoning and procedural complications
Sunburn
|
0.00%
0/46 • All adverse events (AEs) were collected from randomisation (Visit 2, Day 1) until the follow-up visit (Visit 5).
Visits 2, 3 and 4 comprised 3 separate treatment periods with a washout period of 7 - 10 days between administrations.
|
0.00%
0/48 • All adverse events (AEs) were collected from randomisation (Visit 2, Day 1) until the follow-up visit (Visit 5).
Visits 2, 3 and 4 comprised 3 separate treatment periods with a washout period of 7 - 10 days between administrations.
|
2.2%
1/45 • Number of events 1 • All adverse events (AEs) were collected from randomisation (Visit 2, Day 1) until the follow-up visit (Visit 5).
Visits 2, 3 and 4 comprised 3 separate treatment periods with a washout period of 7 - 10 days between administrations.
|
|
Investigations
Weight Decreased
|
0.00%
0/46 • All adverse events (AEs) were collected from randomisation (Visit 2, Day 1) until the follow-up visit (Visit 5).
Visits 2, 3 and 4 comprised 3 separate treatment periods with a washout period of 7 - 10 days between administrations.
|
2.1%
1/48 • Number of events 1 • All adverse events (AEs) were collected from randomisation (Visit 2, Day 1) until the follow-up visit (Visit 5).
Visits 2, 3 and 4 comprised 3 separate treatment periods with a washout period of 7 - 10 days between administrations.
|
0.00%
0/45 • All adverse events (AEs) were collected from randomisation (Visit 2, Day 1) until the follow-up visit (Visit 5).
Visits 2, 3 and 4 comprised 3 separate treatment periods with a washout period of 7 - 10 days between administrations.
|
|
Investigations
White Blood Cell Count Decreased
|
0.00%
0/46 • All adverse events (AEs) were collected from randomisation (Visit 2, Day 1) until the follow-up visit (Visit 5).
Visits 2, 3 and 4 comprised 3 separate treatment periods with a washout period of 7 - 10 days between administrations.
|
2.1%
1/48 • Number of events 1 • All adverse events (AEs) were collected from randomisation (Visit 2, Day 1) until the follow-up visit (Visit 5).
Visits 2, 3 and 4 comprised 3 separate treatment periods with a washout period of 7 - 10 days between administrations.
|
0.00%
0/45 • All adverse events (AEs) were collected from randomisation (Visit 2, Day 1) until the follow-up visit (Visit 5).
Visits 2, 3 and 4 comprised 3 separate treatment periods with a washout period of 7 - 10 days between administrations.
|
|
Nervous system disorders
Headache
|
10.9%
5/46 • Number of events 5 • All adverse events (AEs) were collected from randomisation (Visit 2, Day 1) until the follow-up visit (Visit 5).
Visits 2, 3 and 4 comprised 3 separate treatment periods with a washout period of 7 - 10 days between administrations.
|
12.5%
6/48 • Number of events 7 • All adverse events (AEs) were collected from randomisation (Visit 2, Day 1) until the follow-up visit (Visit 5).
Visits 2, 3 and 4 comprised 3 separate treatment periods with a washout period of 7 - 10 days between administrations.
|
4.4%
2/45 • Number of events 2 • All adverse events (AEs) were collected from randomisation (Visit 2, Day 1) until the follow-up visit (Visit 5).
Visits 2, 3 and 4 comprised 3 separate treatment periods with a washout period of 7 - 10 days between administrations.
|
|
Nervous system disorders
Dizziness
|
0.00%
0/46 • All adverse events (AEs) were collected from randomisation (Visit 2, Day 1) until the follow-up visit (Visit 5).
Visits 2, 3 and 4 comprised 3 separate treatment periods with a washout period of 7 - 10 days between administrations.
|
4.2%
2/48 • Number of events 3 • All adverse events (AEs) were collected from randomisation (Visit 2, Day 1) until the follow-up visit (Visit 5).
Visits 2, 3 and 4 comprised 3 separate treatment periods with a washout period of 7 - 10 days between administrations.
|
0.00%
0/45 • All adverse events (AEs) were collected from randomisation (Visit 2, Day 1) until the follow-up visit (Visit 5).
Visits 2, 3 and 4 comprised 3 separate treatment periods with a washout period of 7 - 10 days between administrations.
|
|
Nervous system disorders
Migraine
|
0.00%
0/46 • All adverse events (AEs) were collected from randomisation (Visit 2, Day 1) until the follow-up visit (Visit 5).
Visits 2, 3 and 4 comprised 3 separate treatment periods with a washout period of 7 - 10 days between administrations.
|
2.1%
1/48 • Number of events 1 • All adverse events (AEs) were collected from randomisation (Visit 2, Day 1) until the follow-up visit (Visit 5).
Visits 2, 3 and 4 comprised 3 separate treatment periods with a washout period of 7 - 10 days between administrations.
|
2.2%
1/45 • Number of events 1 • All adverse events (AEs) were collected from randomisation (Visit 2, Day 1) until the follow-up visit (Visit 5).
Visits 2, 3 and 4 comprised 3 separate treatment periods with a washout period of 7 - 10 days between administrations.
|
|
Nervous system disorders
Lethargy
|
0.00%
0/46 • All adverse events (AEs) were collected from randomisation (Visit 2, Day 1) until the follow-up visit (Visit 5).
Visits 2, 3 and 4 comprised 3 separate treatment periods with a washout period of 7 - 10 days between administrations.
|
2.1%
1/48 • Number of events 1 • All adverse events (AEs) were collected from randomisation (Visit 2, Day 1) until the follow-up visit (Visit 5).
Visits 2, 3 and 4 comprised 3 separate treatment periods with a washout period of 7 - 10 days between administrations.
|
0.00%
0/45 • All adverse events (AEs) were collected from randomisation (Visit 2, Day 1) until the follow-up visit (Visit 5).
Visits 2, 3 and 4 comprised 3 separate treatment periods with a washout period of 7 - 10 days between administrations.
|
|
Nervous system disorders
Presyncope
|
0.00%
0/46 • All adverse events (AEs) were collected from randomisation (Visit 2, Day 1) until the follow-up visit (Visit 5).
Visits 2, 3 and 4 comprised 3 separate treatment periods with a washout period of 7 - 10 days between administrations.
|
2.1%
1/48 • Number of events 1 • All adverse events (AEs) were collected from randomisation (Visit 2, Day 1) until the follow-up visit (Visit 5).
Visits 2, 3 and 4 comprised 3 separate treatment periods with a washout period of 7 - 10 days between administrations.
|
0.00%
0/45 • All adverse events (AEs) were collected from randomisation (Visit 2, Day 1) until the follow-up visit (Visit 5).
Visits 2, 3 and 4 comprised 3 separate treatment periods with a washout period of 7 - 10 days between administrations.
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
2.2%
1/46 • Number of events 1 • All adverse events (AEs) were collected from randomisation (Visit 2, Day 1) until the follow-up visit (Visit 5).
Visits 2, 3 and 4 comprised 3 separate treatment periods with a washout period of 7 - 10 days between administrations.
|
0.00%
0/48 • All adverse events (AEs) were collected from randomisation (Visit 2, Day 1) until the follow-up visit (Visit 5).
Visits 2, 3 and 4 comprised 3 separate treatment periods with a washout period of 7 - 10 days between administrations.
|
2.2%
1/45 • Number of events 1 • All adverse events (AEs) were collected from randomisation (Visit 2, Day 1) until the follow-up visit (Visit 5).
Visits 2, 3 and 4 comprised 3 separate treatment periods with a washout period of 7 - 10 days between administrations.
|
|
Skin and subcutaneous tissue disorders
Dermatitis Acneiform
|
0.00%
0/46 • All adverse events (AEs) were collected from randomisation (Visit 2, Day 1) until the follow-up visit (Visit 5).
Visits 2, 3 and 4 comprised 3 separate treatment periods with a washout period of 7 - 10 days between administrations.
|
2.1%
1/48 • Number of events 1 • All adverse events (AEs) were collected from randomisation (Visit 2, Day 1) until the follow-up visit (Visit 5).
Visits 2, 3 and 4 comprised 3 separate treatment periods with a washout period of 7 - 10 days between administrations.
|
2.2%
1/45 • Number of events 1 • All adverse events (AEs) were collected from randomisation (Visit 2, Day 1) until the follow-up visit (Visit 5).
Visits 2, 3 and 4 comprised 3 separate treatment periods with a washout period of 7 - 10 days between administrations.
|
|
Skin and subcutaneous tissue disorders
Acne
|
2.2%
1/46 • Number of events 1 • All adverse events (AEs) were collected from randomisation (Visit 2, Day 1) until the follow-up visit (Visit 5).
Visits 2, 3 and 4 comprised 3 separate treatment periods with a washout period of 7 - 10 days between administrations.
|
0.00%
0/48 • All adverse events (AEs) were collected from randomisation (Visit 2, Day 1) until the follow-up visit (Visit 5).
Visits 2, 3 and 4 comprised 3 separate treatment periods with a washout period of 7 - 10 days between administrations.
|
0.00%
0/45 • All adverse events (AEs) were collected from randomisation (Visit 2, Day 1) until the follow-up visit (Visit 5).
Visits 2, 3 and 4 comprised 3 separate treatment periods with a washout period of 7 - 10 days between administrations.
|
|
Skin and subcutaneous tissue disorders
Rash
|
2.2%
1/46 • Number of events 1 • All adverse events (AEs) were collected from randomisation (Visit 2, Day 1) until the follow-up visit (Visit 5).
Visits 2, 3 and 4 comprised 3 separate treatment periods with a washout period of 7 - 10 days between administrations.
|
0.00%
0/48 • All adverse events (AEs) were collected from randomisation (Visit 2, Day 1) until the follow-up visit (Visit 5).
Visits 2, 3 and 4 comprised 3 separate treatment periods with a washout period of 7 - 10 days between administrations.
|
0.00%
0/45 • All adverse events (AEs) were collected from randomisation (Visit 2, Day 1) until the follow-up visit (Visit 5).
Visits 2, 3 and 4 comprised 3 separate treatment periods with a washout period of 7 - 10 days between administrations.
|
|
Vascular disorders
Haematoma
|
4.3%
2/46 • Number of events 2 • All adverse events (AEs) were collected from randomisation (Visit 2, Day 1) until the follow-up visit (Visit 5).
Visits 2, 3 and 4 comprised 3 separate treatment periods with a washout period of 7 - 10 days between administrations.
|
0.00%
0/48 • All adverse events (AEs) were collected from randomisation (Visit 2, Day 1) until the follow-up visit (Visit 5).
Visits 2, 3 and 4 comprised 3 separate treatment periods with a washout period of 7 - 10 days between administrations.
|
0.00%
0/45 • All adverse events (AEs) were collected from randomisation (Visit 2, Day 1) until the follow-up visit (Visit 5).
Visits 2, 3 and 4 comprised 3 separate treatment periods with a washout period of 7 - 10 days between administrations.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee Neither Party (PI or Sponsor) will use the other Party's name in connection with any publication or promotion without the other Party's prior, written consent.
- Publication restrictions are in place
Restriction type: OTHER